1,5-Hydrogen Atom Transfer/Surzur–Tanner Rearrangement: A Radical Cascade Approach for the Synthesis of 1,6-Dioxaspiro[4.5]decane and 6,8-Dioxabicyclo[3.2.1]octane Scaffolds in Carbohydrate Systems

Abstract

The 1,5-HAT–1,2-(ester)alkyl radical migration (Surzur–Tanner rearrangement) radical/polar sequence triggered by alkoxyl radicals has been studied on a series of C-glycosyl substrates with 3-C-(α,β-d,l-glycopyranosyl)1-propanol and C-(α-d,l-glycopyranosyl)methanol structures prepared from chiral pool d- and l-sugar. The use of acetoxy and diphenoxyphosphatoxy as leaving groups provides an efficient construction of 10-deoxy-1,6-dioxaspiro[4.5]decane and 4-deoxy-6,8-dioxabicyclo[3.2.1]octane frameworks. The alkoxyl radicals were generated by the reaction of the corresponding N-alkoxyphthalimides with group 14 hydrides [n-Bu₃SnH(D) and (TMS)₃SiH], and in comparative terms, the reaction was also initiated by visible light photocatalysis using the Hantzsch ester/fac-Ir(ppy)₃ procedure. Special attention was devoted to the influence of the relative stereochemistry of the centers involved in the radical sequence on the reaction outcome. The addition of BF₃•Et₂O as a catalyst to the radical sequence resulted in a significant increase in the yields of the desired bicyclic ketals.

Introduction

The development of synthetic methodologies for bicyclic 1,6-dioxaspiro[4.5]decane¹ and 6,8-dioxabicyclo[3.2.1]octane (6,8-DOBCO)² scaffolds is largely stimulated by their occurrence as the structural core of highly active insect pheromones.³ They can also be widely found as subunits⁴ in the structure of other more complex and biologically important natural products such as steroids,⁵ polyether ionophores,⁶ and marine toxins.⁷ In some cases, both structural motifs are present in the same natural skeleton, as occurs in pinnatoxins and the related pteriatoxins, potent neurotoxins of a dinoflagellate origin.⁸ Moreover, both bicyclic ketals have attracted much interest from synthetic chemists as versatile building blocks in fine organic synthesis.⁹

In the carbohydrate field, the preparation of spiro-heterocycles has been recently reviewed.¹⁰ Several naturally occurring 2,7-anhydro-β-d-glyco-hept-2-ulopyranose sugars with 6,8-dioxabicyclo[3.2.1]octane structures have been described. The most representative example is sedoheptulosan (2,7-anhydro-β-d-altro-hept-2-ulopyranose), although analogous compounds with d-gluco and d-manno stereochemistry are also known.¹¹

In previous papers, we reported on a new procedure for the stereoselective construction of 1,6-dioxaspiro[4.5]decane¹² and 6,8-dioxabicyclo[3.2.1]octane¹³ frameworks on carbohydrate models as described in Scheme 1. Under mild oxidative conditions (PhI(OAc)₂/I₂), the initially generated alkoxyl radicals (i.e., I and II, PGO) trigger a 1,5-hydrogen atom transfer (1,5-HAT)¹⁴–radical oxidation–nucleophilic cyclization through a radical/polar crossover sequence that ultimately leads to the desired bicycles (i.e., III and IV, respectively) in a single step. In some cases, [4.5] spiroketal systems with a kinetic nonanomeric unstable configuration at the spiro center can be preferentially obtained using this methodology. Also using this simple procedure, natural C-glycosyl compounds of a C-(1,6-anhydro-β-d-glyco-1-ulopyranosyl)methanol structure (i.e., IV) with rare stereochemistries d-ido, d-gulo, and d-altro can be obtained from readily available d-gluco, d-galacto, and d-manno chiral pool sugars, respectively.¹³

Scheme 1. 1,5-HAT Reactions of 3-C-(Glycopyranosyl)propan-1-O-yl and C-(Glycopyranosyl)methan-1-O-yl Radicals.

S–T = Surzur–Tanner; RPC = radical polar crossover; HAT = hydrogen atom transfer.

Otherwise, the generation of the above-mentioned alkoxyl radicals (i.e., I and II, PGO) under reductive conditions proceeds by a different mechanism that allows the preparation of interesting and highly versatile chiral synthons. Homolytic intermolecular allylmethalation of the intermediate C1 radical may lead to C-ketosides (i.e., V, R = All).¹⁵ The regioselective HAT by alkoxyl radicals of the H5 enables also the C5-allylation and the possibility of preparing C-ketosides on both sides of the pyranosyl ring oxygen.¹⁶ Although, at first glance, the homolytic reduction of the C1- and C5-radical intermediates might seem of little synthetic utility, it allows a diastereoselective interconversion between d- and l-C-glycosides (i.e., VI)¹⁷ and α- and β-C-glycosides (i.e., V, R = H), which is difficult to achieve using conventional methods.¹⁸

Since the discovery by Surzur and Teissier¹⁹ and by Tanner and Law²⁰ in the 1960s that β-(acyloxy)alkyl radicals undergo a 1,2-suprafacial migration of their ester group, this rearrangement has attracted considerable mechanistic and synthetic attention.²¹ The use of β-(phosphatoxy)alkyl radicals²² with a better leaving group (LG) and complexation with Lewis acids²³ notably increase the reaction rate and consequently its importance from a synthetic point of view.

In carbohydrate chemistry, this rearrangement has been exploited for a convenient synthesis of 2-deoxypyranoses from 1-pyranosyl radicals²⁴ and in the stereoselective preparation of purine and pyrimidine α-nucleosides.²⁵ This rearrangement is also involved in the DNA and RNA strand scission from 2’- and 4’-radicals via the cleavage of the β-phosphate.²⁶

It is evident that if we end the above-mentioned 1,5-HAT sequences with a β-(acyloxy)alkyl radical (i.e., I and II, LG), a simple and versatile preparation of 2-deoxy-C-glycosides on a 1-ulopyranose ring system (i.e., VII and VIII) could be achieved, where the HAT and the vicinal deoxygenation through an alkene radical-cation intermediate would occur in the same synthetic step. In fact, we would gain access to a series of ketoses with 5-deoxy-non-4-ulopyranose (i.e., VII) and 5-deoxy-hept-6-ulopyranose (also named 3-deoxy-hept-2-ulopyranose) (i.e., VIII) structures by long-range selective oxidation at C1 and C5 ring carbon atoms, respectively. The synthetic interest is apparent; the 3-deoxy-hept-2-ulopyranose framework present in VIII is intimately related to the ring system of octulosonic (Kdo, Kdn) and sialic acids.²⁷ Procedures for the preparation of analogous [4.5] spiroketals in 2-deoxy-pyranose systems using different methodologies have been described in previous publications.²⁸ In general, deoxy-pyranoses are important targets and are frequently found in bioactive secondary metabolites of microbial origin.²⁹

In this paper, the 1,5-HAT–Surzur–Tanner (S–T) radical/polar sequence has been studied principally on a series of C-glycosyl substrates with 3-C-(glyco)1-propanol (i.e., I, LG) and C-(glyco)methanol (i.e., II, LG) structures prepared from chiral pool d- and l-sugar and with α- and β-configurations at the anomeric center. The initial alkoxyl radicals were generated by homolytic cleavage of the corresponding N-alkoxyphthalimide derivatives using the n-Bu₃SnH/AIBN protocol under several different conditions.³⁰ In most cases, the reaction finishes with an intramolecular nucleophilic 5-cyclization at the cine position of the radical-cation–LG anion pair intermediate to give the expected bicyclic acetal (i.e., VII or VIII) with a deoxygenated carbon atom at the vicinal position.^21e

To unambiguously determine the fate of the radical throughout the cascade sequence, the experiments will also be performed with n-Bu₃SnD/AIBN. This will allow us, among other things, to detect whether in the last step of the sequence the β-elimination of the ester takes place by the expected radical-polar β-(ester)alkyl shift mechanism or by a competitive pure radical β-(ester)alkyl fragmentation.²¹ Additionally, the influence of boron trifluoride as a catalyst on the sequence outcome will be addressed. In comparative terms, the reaction was also initiated by visible light photocatalysis using the Hantzsch ester/fac-Ir(ppy)₃ procedure.³¹ In all cases, the reactions were allowed to proceed until the complete consumption of the radical precursors as indicated by TLC.

Due to the stereochemical requirements for the HAT reaction transition state,³² much attention has been paid to the not always apparent conformation of the sugar rings in these C-glycosyl compounds. For this purpose, the ³J_HCCH vicinal ring coupling constants were extracted from the experimental 1D ¹H NMR spectra by iterative simulation³³ and compared with the values calculated on minimized structures in ⁴C₁ and ¹C₄ conformations [see Tables S1 and S2 in the Supporting Information (SI)].³⁴

Previous examples of the HAT–S–T rearrangement sequence have been reported in the formation of tetrahydrofurans from β-(phosphatoxy)alkyl radicals³⁵ and as a key step in the synthesis of cephalosporolide E.³⁶ We have also described another example of this sequence during the reaction of methyl 2,3,4-tri-O-acetyl-6-deoxy-α-d-Talp-(1 → 4)-2,3-di-O-methyl-α-d-Glcp-6-O-yl disaccharide radical.³⁷ The initial 1,8-HAT(6^IO^• → 5^IIC^•) between the two sugars generated a 4^IIβ-(acetoxy)5^II-alkyl radical that led finally to the formation of a rare eight-membered 4^II-deoxy-1,3,5-trioxocane ring system. The use of n-Bu₃SnD confirms that, at least in part, the last step of the sequence involves an S–T rearrangement through a cine 8-exo-substitution mechanism. On the other hand, unsuccessful attempts to trap the intermediate alkene radical cation intramolecularly by carboxylate anions have been reported.³⁸

To obtain a complete picture of the stereochemical influence of the substituents in the course of the radical sequence, we have prepared 3-C-(glycopyranosyl)1-propoxyphthalimides with α,β-d-gluco (1–4), α,β-d-manno (5–8), α-l-fuco (9 and 10), and α,β-d-arabino (11 and 12) configurations (Scheme 4).³⁹ A few examples of 3-C-(α-d-ribofuranosyl)1-propoxyphthalimides (13–15) have been included in this work to study the influence of the greater conformational flexibility of the five-membered ring (Scheme 5). Furthermore, C-(glycopyranosyl)N-methoxyphthalimides with α-d-gluco (16–19), α-d-galacto (20 and 21), α-l-rhamno (22), and α-l-fuco (23 and 24) configurations (Scheme 6) have also been synthesized (Schemes 4–6 are presented later in this work). In most of these models, it has been possible to investigate the differences between the migratory capabilities of acetoxy and diphenoxyphosphatoxy groups and how they affect the final result of the sequence.⁴⁰

Scheme 4. Synthesis of 3-C-(Glycopyranosyl)1-propoxyphthalimide (1–12) Precursors of 1,6-Dioxaspiro[4.5]decane Structures.

Reagents and conditions: (a) (i) BH₃•THF 1 M complex, THF, 0 °C to rt, 1 h. (ii) NaOH 3 M, H₂O₂ 30%, 0 °C, 1 h. (b) HONPhth, Ph₃P, DEAD, THF, 0 °C to rt, 1–4 h. (c) Ac₂O, Py, DMAP, 0 °C to rt, 1 h. (d) ClPO(OPh)₂, DMAP, CH₂Cl₂, 0 °C to rt, 2 h. (e) (i) I₂, CH₂Cl₂, rt, 3 h. (ii) Zn dust, AcOH, Et₂O:MeOH, rt, overnight. (f) (i) allyltrimethylsilane, BF₃•Et₂O, CH₃CN, 0 °C to rt, 1.5 h. (ii) Na₂CO₃, MeOH, rt, 2.5 h. (iii) PhCH(OMe)₂, CSA, DMF, rt, overnight. (g) (i) HONPhth, Ph₃P, DEAD, THF, 0 °C to rt, 0.5 h. (ii) ClPO(OPh)₂, DMAP, CH₂Cl₂, 0 °C to rt, 1.5 h. (h) TFA/H₂O, CH₂Cl₂, 0 °C to rt, 1 h.

Values in parentheses are isolate yields.

Scheme 5. Synthesis of 3-C-(α-d-Ribofuranosyl)1-propoxyphthalimide (13–15) Precursors of 1,6-Dioxaspiro[4.4]nonane Structures.

Reagents and conditions: (a) DPSCl, imidazole, DMF, 0 °C, 0.5 h. (b) (i) BH₃•THF 1 M complex, THF, 0 °C to rt, 2.5 h. (ii) NaHCO₃, H₂O₂ 30%, 0 °C, 1 h. (c) (i) HONPhth, Ph₃P, DEAD, 50 °C, 2 h. (ii) Ac₂O, DMAP, Py, rt, 1 h. (d) (i) HONPhth, Ph₃P, DEAD, 50 °C, 2 h. (ii) Tf₂O, Py, rt, 1 h. (e) 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, Py, 0 °C, 20 h. (f) HONPhth, Ph₃P, DEAD, 50 °C, overnight. (g) ClPO(OPh)₂, DMAP, CH₂Cl₂, rt, 3 h.

Values in parentheses are isolate yields.

Scheme 6. Synthesis of C-(Glycopyranosyl)N-methoxyphthalimide Precursors of 6,8-Dioxabicyclo[3.2.1]heptane Structures.

Reagents and conditions: (a) Ac₂O, Py, DMAP, rt, 0.5–1.5 h. (b) (i) propargyl trimethylsilane/Et₂O 39% v/v, TMSOTf, CH₃CN, sonication, rt, 1.5–3 h. (ii) DPSCl, imidazole, DMF, 0 °C, 2 h. (c) (i) O₃, CH₂Cl₂–MeOH, −78 °C. (ii) NaBH₄, 0 °C to rt, 1–3 h. (d) HONPhth, Ph₃P, DEAD, 0 °C, 1.5 h–overnight. (e) (i) K₂CO₃, MeOH, rt, overnight. (ii) ClPO(OPh)₂, DMAP, CH₂Cl₂, rt, 2.5–7 h. (f) (i) K₂CO₃, MeOH, rt, overnight. (ii) TsCl, Py, rt, overnight. (g) (i) DHP, p-TsOH•H₂O, CH₂Cl₂, rt, 2 h. (ii) TBAF/THF 1 M, THF, rt, 3 h. (iii) K₂CO₃, MeOH, rt, 4 h. (iv) ClPO(OPh)₂, Py, rt, overnight. (h) NaH 60%, p-TsO-CHD-Ph, DMF/CH₂Cl₂, rt, 1 h. (i) BF₃•OEt₂, TMSOTf, propargyl trimethylsilane, CH₃CN, 0 °C to rt, 15 h. (j) (i) K₂CO₃, MeOH, rt, 3 h. (ii) 2,2-dimethoxypropane, p-TsOH•H₂O, acetone, rt, 3 h. (iii) NaH 60%, BnBr, DMF, 0 °C, 3 h. (k) (i) TFA/H₂O, rt, 2 h. (ii) NaH 60%, MeI, DMF, 0 °C, 1.5 h. (iii) O₃, CH₂Cl₂–MeOH, −78 °C. (iv) NaBH₄, 0 °C to rt, 0.75 h. (l) (i) H₂, Pd/C 10%, EtOAc, rt, overnight. (ii) HONPhth, Ph₃P, DEAD, 0 °C to rt, 3.5 h. (m) ClPO(OPh)₂, DMAP, CH₂Cl₂, rt, 2 h. (n) (i) K₂CO₃, MeOH, rt, 3 h. (ii) 2,3-butanedione, (MeO)₃CH, BF₃•Et₂O, MeOH, 60 °C, 4.5 h. (o) (i) NaH 60%, BnBr, DMF, 0 °C, 2 h. (ii) TFA/H₂O, 40 °C, overnight. (iii) NaH 60%, MeI, DMF, 0 °C to rt, 2 h. (iv) O₃, CH₂Cl₂–MeOH, −78 °C. (v) NaBH₄, 0 °C to rt, 1 h. (p) (i) DPSCl, imidazole, DMF, rt, 3 h. (ii) H₂, Pd/C 10%, EtOAc, rt, overnight. (iii) Ac₂O, Py, DMAP, rt, 0.5 h. (iv) TBAF/THF, 1 M, THF, rt, 4 h. (q) (i) DPSCl, imidazole, DMF, rt, 3 h. (ii) H₂, Pd/C 10%, EtOAc, rt, overnight. (iii) ClPO(OPh)₂, DMAP, CH₂Cl₂, rt, 3.5 h. (iv) TBAF/THF, 1 M, THF, rt, 3.5 h.

Values in parentheses are isolate yields.

Results and Discussion

Synthesis of 10-Deoxy-1,6-dioxaspiro[4.5]decane and 9-Deoxy-1,6-dioxaspiro[4.4]nonane Scaffolds

The results of the study with 3-C-(α,β-d-Glcp)propan-1-O-yl radicals using 2-acetyl and 2-diphenoxyphosphoryl as LGs are summarized in Table 1. Initial experiments with 3-C-(2-O-acetyl-α-d-Glcp)1-propoxyphthalimide precursor 1 employing conditions optimized for the generation of alkoxyl radicals from N-alkoxyphthalimides using n-Bu₃SnH (1 equiv) in a dilute solution (0.013 M) of toluene at reflux temperature and AIBN as the initiator gave a mixture of three compounds: 25, 26β, and 26α (Table 1, entry 1). The major product 25 was identified as the expected 1,5-HAT–S–T spiroketal. The minor components of the reaction are 26β, which is formed by hydrogen abstraction at C-1 and subsequent radical axial quenching with inversion of configuration, and isomeric alcohol 26α, which could arise either by abstraction and retention of the configuration or simply by premature reduction of the alkoxyl radical. In the latter case, a combination of both mechanisms could be operative and cannot be ruled out at the present stage of the work. The yield of the cyclized product 25 was increased to 50% by lowering the tin hydride concentration with a syringe pump; under these conditions, the C-glucosyl compound 26β could not be detected (Table 1, entry 2). Attempts to improve the yield using (TMS)₃SiH (TTMSS), a group 14 hydride with a smaller hydrogen donor capacity,⁴¹ to avoid the reduction of radical intermediates met with no success.

Table 1. 1,5-HAT–S–T Sequence in 3-C-(α,β-d-Glcp)1-propoxyphthalimides 1–4^a.

^aReagents and conditions: method A: n-Bu₃SnH (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method B: n-Bu₃SnH (1 equiv/h), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method C: TTMSS (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; and method D: n-Bu₃SnD (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux.

^bValues in parentheses are isolate yields; deuterium incorporation (²H/¹H) is included in partially labeled compounds.

Considerable analytical and spectroscopic data were diagnostic of the spiroketal structure of 25, unambiguously expressing the presence of a quaternary ketal carbon and the additional methylene group as well as the disappearance of the acetyl group. In a minimized structure, the pyranose ring adopts preferentially a ⁴C₁ chair conformation, from which the calculated coupling constants were in agreement with the experimental values (see Table S3 in the SI). The configuration of the spiro center was tentatively assigned as 1S, with the anomeric oxygen in an axial position,⁴² according to the downfield displacement observed for the H3 and H5 protons that in this conformation present 1,3-diaxial interactions with the C1–O bond. In addition, the absence of NOE interactions between H1’ and H5 and/or H3 that were present in previously reported analogous [4.5] spiroketals in 2-deoxy-pyranose systems with 1R stereochemistry may also support this assignment.^28a

The use of n-Bu₃SnD showed the quantitative monodeuteration for (2-²H)25 and for the inverted product (1-²H)26β (Table 1, entry 4). Moreover, the early reduction of the alkoxyl radical was solely responsible for the unlabeled 26α and no retention at C1 could be detected in this experiment. The diastereoselective ratio (²H_ax/²H_eq, 7:1) of deuterium at (2-²H)25 is mostly attributable to a β-facial preference for the radical quenching due to steric hindrance.

For comparative purposes, we have prepared C-(2-O-diphenoxyphosphoryl-α-d-Glcp)1-propoxyphthalimide 2. The rate constant of the β-(phosphatoxy)alkyl radical migration should be several orders of magnitude greater than that recorded for comparable acyloxy shifts.^21d However, the reaction of 2 with n-Bu₃SnH/AIBN afforded the 1,5-HAT–S–T substitution product 25 in a similar yield (44%) together with a mixture of alcohols that, after acetylation, were identified as 27β and 27α (Table 1, entry 5). The slow addition of n-Bu₃SnH generates the bicycle 25 as a sole product in 53% yield (Table 1, entry 6). The reaction with n-Bu₃SnD showed the complete monodeuteration for the spirocompound (2β-²H)25 achieved in a significantly better yield (62%) (Table 1, entry 7). The inseparable mixture of the complete labeling inverted product (1-²H)28β and the reduced unlabeled alcohol 28α was also obtained (20%, 1:2.1).

This protocol was also applied to C-(2-O-acetyl-β-d-Glcp)1-propoxyphthalimide 3, where the pyranose ring adopts preferentially a ⁴C₁ conformation with the three-carbon tether in an equatorial position and, consequently, the abstractable hydrogen atom at C1 is axially oriented (see Table S1 in the SI). Unfortunately, treatment of 3 under the same conditions mentioned above did not increase the yield of 25 (Table 1, compare entries 8–10 with 1–3). Now, the principal compound is C-glucosyl compound 26β, and according to the reaction with n-Bu₃SnD, approximately 50% is formed by prereduction of the alkoxyl radical {[1-²H]26β (²H/¹H, 1:1)} (Table 1, entry 11). These results were rather unexpected since electrophilic radicals abstract axial hydrogen atoms much faster than the equatorial ones and the initial 1,5-HAT should be favored relative to our previous models 1 and 2.⁴³ The different reactivity between 1 and 3 can be explained by a possible memory of chirality effect of the C1 radical after the 1,5-HAT reaction (Table 1, compare entries 1 and 8).⁴⁴

Moreover, the migration of a phosphatoxy group contributed to a marked improvement in the yield of 25 as shown in model 4 (Table 1, entries 12–14). Under these conditions, no appreciable amounts of C-glucosyl compounds resulting from the reduction of intermediate radicals were detected. As observed in previous models, the yield of the spiroketal increased significantly when changing from a hydride donor 25 to a less reactive deuteride donor (2-²H)25 (Table 1, compare entries 12 and 14). These results probably reflect a kinetic isotope effect (KIE) in which a slower process permits the radical to reach the end of the sequence, avoiding prereduction and the formation of uncyclized products.

The reaction of an analogous series of 3-C-(α,β-d-Manp)propan-1-O-yl radicals using also 5-acetyl and 5-diphenoxyphosphatoxy as LGs is summarized in Table 2. The 3-C-(2-O-acetyl-α-d-Manp)1-propoxyphthalimide 5 under the classical tin hydride conditions afforded exclusively uncyclized compounds 29β and 29α, as confirmed by deuterium labeling experiments (Table 2, entries 1 and 2). The expected spiroketal 25 could not be detected.

Table 2. 1,5-HAT–S–T Sequence in 3-C-(α,β-d-Manp)1-propoxyphthalimides 5–8^a.

^aReagents and conditions: method A: n-Bu₃SnH (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method B: n-Bu₃SnH (1 equiv/h), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method C: TTMSS (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method D: n-Bu₃SnD (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method E: n-Bu₃SnD (1 equiv), BF₃•Et₂O (0.2 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method F: Hantzsch ester (1.1 equiv), fac-Ir(ppy)₃ (0.01 equiv), THF (0.007 M), rt, blue LED; and method G: Hantzsch ester (0.37 equiv/h), fac-Ir(ppy)₃ (0.01 equiv), THF (0.007 M), rt, blue LED.

^bValues in parentheses are isolate yields; deuterium incorporation (²H/¹H) is included in partially labeled compounds.

The isomeric β-phthalimide 7 behaved similarly, with only 29β (97%) being obtained (Table 2, entry 7). Under tin deuteride conditions, the reaction gave [1-²H]29β (²H/¹H, 5.8:1); the labeled compound originated by deuterium incorporation with retention after the 1,5-HAT and the unlabeled compound by direct reduction of the alkoxyl radical (Table 2, entry 10). Knowing that aluminum and scandium Lewis acid can efficiently enhance the rate of the S–T rearrangement,²³ we envisioned an experiment that under the same conditions [n-Bu₃SnD (1 equiv), AIBN (0.1 equiv), and PhCH₃ (0.013 M) at 110 °C] contains a catalytic amount of BF₃•Et₂O (0.2 equiv). To our delight, the radical sequence now proceeded nicely to the end, furnishing the desired product [2-²H]25 in 50% yield along with a small amount of [1-²H]29β (19%) (Table 2, entry 11). The ¹H NMR analysis of the deuterium incorporation at [2-²H]25 (²H/¹H, 1.6:1) revealed that, in this case, the β-elimination of the ester could take place not only by the radical-polar β-(acyloxy)alkyl shift mechanism but also by a competitive pure radical β-(acyloxy)alkyl fragmentation.⁴⁵ Alternatively, acid-catalyzed opening and recombination of the spiroketal ring through an unobserved glucal intermediate [3-C-(1,5-anhydro-2-deoxy-d-arabino-hex-1-enopyranosyl)propan-1-ol] may also account for the loss of deuterium detected.

The 3-C-(2-O-diphenoxyphosphoryl-α,β-d-Manp)1-propoxyphthalimide models 6 and 8 with a faster migratory group gave, under standard tin hydride conditions, spiroketal 25 in moderate yields (Table 2, entries 3 and 12, respectively). The yields of (2-²H)25 improved using tin deuteride (52% in both cases) and increased notably upon Lewis acid catalysis giving [2-²H]25 (65%, ²H/¹H, 2.4:1) by partial labeling (Table 2, entries 4, 14, and 15). The difference in reactivity between 2-acetyl-d-gluco (1 and 3) and -d-manno derivatives (5 and 7) has been attributed to the observed lower migration efficiency of axial β-(acetoxy)alkyl radicals.^24b,46

The formation of alkoxyl radicals from N-alkoxyphthalimide under photoredox catalysis conditions and their use in selective C(sp³)–H functionalization through 1,5-HAT have been recently reported.,^31b47 As far as we know, this type of methodology has never been employed to initiate the 1,5-HAT–S–T sequence described in this paper. The blue LED irradiation of phthalimides 6 and 8 in the presence of a catalytic amount of fac-[Ir(ppy)₃] and Hantzsch ester as the reductant afforded spirocycle 25 in a disappointingly low yield, with the prereduced alcohols 30α and 30β, respectively, being the major products (Table 2, entries 5 and 16). Although the yield of 25 increased slightly by slowly adding the Hantzsch ester to the reaction mixture using a syringe pump, it is still clearly inferior to the results obtained with the tin hydrides (Table 2, entries 6 and 17).

Next, this study was extended to the acetyl and diphenoxyphosphoryl 3-C-(α-l-Fucp)1-propoxyphthalimides 9 and 10, respectively, as described in Table 3. When the 2-acetyl precursor 9 was treated with n-Bu₃SnH/AIBN, the main product was the expected spirocycle 31 (46%) together with an inseparable mixture (2:3, 15%) of two minor alcohols: 6-deoxy-d-altro32 and l-fuco33 (Table 3, entry 1). Although both diastereomers can be tentatively identified by NMR analysis of the mixture, additional support for these structures came from the complete separation and characterization of diphenoxyphosphoryl analogues 34 and 35 achieved during the reaction of phthalimide 10 (Table 3, entry 5).

Table 3. 1,5-HAT–S–T Sequence in 3-C-(α-l-Fucp)- and 3-C-(d-Arap)1-propoxyphthalimides 9–12^a.

^aReagents and conditions: method A: n-Bu₃SnH (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method D: n-Bu₃SnD (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method E: n-Bu₃SnD (1 equiv), BF₃•Et₂O (0.2 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method F: Hantzsch ester (1.1 equiv), fac-Ir(ppy)₃ (0.01 equiv), THF (0.007 M), rt, blue LED; and method G: Hantzsch ester (0.37 equiv/h), fac-Ir(ppy)₃ (0.01 equiv), THF (0.007 M), rt, blue LED.

^bValues in parentheses are isolate yields; deuterium incorporation (²H/¹H) is included in partially labeled compounds. dr = diastereomeric ratio; only the major isomer is shown.

The spiroketal 31 with a nonanomeric configuration at the spirocenter was isolated and contaminated with a small amount of the thermodynamic isomer (1S/1R, 85:15). In both isomers, the pyranosyl ring preferentially adopts a ¹C₄ chair conformation (see Table S3 in the SI). The ¹H NMR spectrum of 31 shows a ⁴J_w coupling (1.3 Hz, calcd 1.3 Hz)⁴⁸ between H2α and H4 equatorial hydrogens, which also supports the mentioned conformation (see Table S4 in the SI). The 1S configuration of the major isomer (shown in Table 3) was established based on the NOE interactions observed between H5 and H1’ and H2’. The downfield displacement observed for H3 (0.1 ppm) and H5 (0.3 ppm) in the ¹H NMR spectrum of the minor 1R-isomer lends further evidence to the proposed spiroketal stereochemistry.

Several interesting conclusions can be drawn from the results obtained during the deuteration experiment (Table 3, entry 2). Compound [PhCH-²H]31 (D/H = 1.5:1; dr = 4:1) showed no significant incorporation of deuterium at the C2 site, but instead a partial deuteration of a benzylic proton at C4 could be detected. The quantitative incorporation of deuterium confirmed that the 6-deoxy-d-altrose derivative (5-²H)32 was formed by the reductive inversion of configuration of a 5-radical intermediate. Finally, the undeuterated alcohol 33 was formed exclusively by prereduction of the initial alkoxyl radical. All our attempts to obtain spirocyclic 31 by applying the photoredox conditions mentioned above were unsuccessful, with only prereduced alcohol 33 being isolated instead (Table 3, entries 3 and 4).

The reaction of 3-C-(2-diphenoxyphosphoryl-α-l-Fucp)1-propoxyphthalimide 10 provided the desired bicycle 31 in better yield (52%) together with small amounts of the 6-deoxy-d-altro34 and l-fuco35 derivatives that could now be conveniently characterized. The 6-deoxy-β-d-altropyranosyl ring in 34 exists preferentially in a ⁴C₁ conformation with the two alkyl residues in an equatorial position, with the value of the ³J_4,5 = 9.8 Hz (calcd = 8.4 Hz) confirming the inversion of configuration at C5. Furthermore, a new compound 36 with a 2,7-dioxabicyclo[4.4.0]decane skeleton, hitherto undetected in the reaction of previous models, was also isolated in 10% yield (Table 3, entry 5). The structure and stereochemistry of 36, a constitutional isomer of 31, were readily established by analytic and spectroscopic means. Most significantly, the ³J fucopyranosyl ring coupling constants extracted by DAISY from the experimental spectrum and NOE interactions of H1 with H3 and H5, and H2 with H1’ confirmed the trans-fused bis(pyran) proposed framework.⁴⁹

A possible propagation cycle for the acetyl and diphenoxyphosphoryl 3-C-(α-l-Fucp)propan-1-O-yl radical chain reactions, employing tin deuteride as reductant, is outlined in Scheme 2. The electrophilic alkoxyl radical (I) triggers two competitive hydrogen atom transfer reactions by abstraction of stereochemically accessible 1H (1,5-HAT) and 5H (1,7-HAT). Many examples of 1,5-hydrogen translocations are known; however, their 1,7-HAT counterparts are comparatively very scarce.^14,50 The 5-alkyl radical (II) leads finally to 3-C-(6-deoxy-β-d-altropyranosyl)1-propanol derivatives (5-²H)32 and (5-²H)34 with inversion of configuration. The 1-alkyl radical (III) continues the cascade sequence by the two mechanisms mentioned before: pure radical β-fragmentation to give unlabeled 31, through a non-isolated olefin, and S–T rearrangement through the radical-polar intermediate (IV).⁴⁵ When phosphate is used as LG, the reaction is directed toward two competitive pathways: cine and ipso intramolecular cyclization by the primary alcohol that now acts as a nucleophile. The minor ipso cyclization affords the bis(pyran) (1-²H)36 through radical (V). Furthermore, the cine substitution provides 2-radical (VI) that regioselectively abstracts a benzylic hydrogen from the 4-OBn protecting group by means of another 1,5-HAT process. Consequently, no deuterium incorporation (within the limits of NMR detection) was observed at C2. Reductive quenching of radical VII leads to the quantitatively deuterated (PhCH-²H)31, isolated together with the unlabeled 31 formed by the β-fragmentation mechanism.

Scheme 2. Propagation Cycle of 3-C-(α-l-Fucp)propan-1-O-yl Radicals.

The prereduction of the alkoxyl radical and the initiation and termination steps are omitted for clarity.

The ¹H and ¹³C{¹H} NMR spectra of isolated [PhCH-²H]31 (D/H, 1.5:1; dr = 4:1) deserve some comments. The deuteration at 4-OBn is highly stereoselective, providing evidence for a steric hindered deuteride addition. Both diastereoisomeric deuterated benzyl ethers seem to adopt two different conformations that affect the chemical shift displacement of surrounding protons and carbons. Thus, for example, the 6-methyl group signal appears as three doublets of approximately the expected intensities (1.5:0.3:1.2): 1.130 ppm (J = 6.3 Hz, D major), 1.133 ppm (J = 6.6 Hz, D minor), and 1.135 ppm (J = 6.3 Hz, unlabeled) (see Table S5 and Figure S1 in the SI for details).

This anomalous behavior that may be attributable to the aromatic ring current effect can also be observed in its ¹³C{¹H} NMR spectrum; the C4 atom appears as three signals: 74.97 ppm (D major), 75.02 ppm (D minor), and 75.09 ppm (unlabeled), also with intensities in accordance with the relative proportions (see Table S6 and Figure S3 in the SI for details).

This effect has not been detected in analogous monodeuterated 4-OBn compounds with a d-glucose configuration described in the literature.⁵¹ In an attempt to rationalize this unexpected NMR result, we prepared methyl 4-O-benzyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-[4-O-PhCH-²H]galactopyranoside ([PhCH-²H]97) by the reaction of alcohol 96 with benzyl α-[²H]-4-methylbenzenesulfonate (Scheme 6).⁵² As expected for a d-sugar, [PhCH-²H]97 adopts a ⁴C₁ conformation, while [PhCH-²H]31 exists preferentially in a ¹C₄ chair. Since the structures of d-galactose and l-fucose are in a pseudoenantiomeric relationship, 4-OBn would have a very similar stereochemical environment in [PhCH-²H]97 to that which it has in the structure of [PhCH-²H]31. Indeed, in the NMR spectra of labeled [PhCH-²H]97 (D/H, 7:1; dr = 1:1), it is also observed how both diastereoisomeric deuterated benzyl ethers affect the chemical displacement of the surrounding protons and carbons differently. For example, in the ¹³C{¹H} NMR spectrum, the C4 atom analogously appears as three signals at 73.56 ppm (D₁), 73.59 ppm (D₂), and 73.64 ppm (unlabeled) with the expected intensities (see Table S6 and Figure S4 in the SI for details).

The effectiveness of this methodology was also tested on a d-pentose structure. Thus, the reaction with n-Bu₃SnH/AIBN of 3-C-(2-O-diphenoxyphosphoryl-α,β-d-arabinopyranosyl)1-propoxyphthalimide derivatives 11 as a mixture of anomers and its deprotected diastereoisomeric pure β-diol 12 afforded exclusively the desired spirocycles 37 and 38, respectively (Table 3, entries 7 and 10). The 2-deoxy-arabinopyranosyl ring adopted preferentially a ¹C₄ conformation (see Table S3 in the SI). Compound 38 was previously described by an alternative glycosylation method using thermodynamic conditions, and a 1R anomeric stabilized configuration was assigned.^28c Consequently, we have not found NOE interaction between H1’ and H3 and/or H5 as in previous thermodynamic spiroketals prepared in this work.

The analysis of the isotopic distribution in [2-²H]37 (²H/¹H, 1:1) and [2-²H]38 (²H/¹H, 2.3:1), obtained by reductive n-Bu₃SnD/AIBN with or without the BF₃•Et₂O catalyst, showed a partial monodeuteration at C2, with the major isotopomer occupying the β-equatorial position (Table 3, entries 8, 9, and 11).

For the sake of completeness, this methodology was also extended to a series of furanosyl models derived from 3-C-(α-d-ribofuranosyl)1-propanol as described in Table 4. When the reaction of acetyl phthalimide 13 was carried out under the n-Bu₃SnH(D)/AIBN conditions, no traces of any compound with a 1,6-dioxaspiro[4.4]nonane skeleton were detected. Only the alcohol 40 was obtained (Table 4, entries 1 and 2). The deuterium composition of [1-²H]40 (²H/¹H, 2:1) indicates that a significant 1,5-HAT reaction has taken place, but the C1-radical intermediate is reduced before the S–T rearrangement occurs. An equimolecular mixture of spirocycles [2-²H]39 (²H/¹H, 1.3:1) was achieved in moderate yield by adding a catalytic amount of BF₃•Et₂O to the reaction medium (Table 4, entry 3). Also in this case, a substantial loss of deuterium at C2 indicated the possibility of competitive mechanisms with the 1,2-β-(acyloxy)alkyl radical migration. A change to a better LG such as triflate 14 increased the rate of S–T rearrangement, and the sequence could now be completed under standard tin hydride conditions (Table 4, entries 5 and 6). However, adding BF₃•Et₂O to the reaction resulted in a very complex mixture containing alcohol 41 as the sole identifiable product. The initiation of the reaction under photoredox catalysis conditions on both phthalimides 13 and 14 afforded poorer results (Table 4, entries 4 and 8).

Table 4. 1,5-HAT–S–T Sequence in 3-C-(α-d-Ribf)1-propoxyphthalimides 13–15^a.

^aReagents and conditions: method A: n-Bu₃SnH (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method D: n-Bu₃SnD (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method E: n-Bu₃SnD (1 equiv), BF₃•Et₂O (0.2 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; and method F: Hantzsch ester (1.1 equiv), fac-Ir(ppy)₃ (0.01 equiv), THF (0.007 M), rt, blue LED.

^bValues in parentheses are isolate yields; deuterium incorporation (²H/¹H) is included in partially labeled compounds. dr = diastereomeric ratio.

The use of diphenylphosphate as in 15 gave access exclusively to spirocycles 42 and 43, isolated as a separable mixture of anomers in 62% overall yield (Table 4, entries 9 and 10). Again, under photoredox conditions, lower yields of the spirocyclic compounds and significant amounts of prematurely reduced alcohol 44 were obtained (Table 4, entry 11).

Synthesis of 4-Deoxy-6,8-dioxabicyclo[3.2.1]octane Scaffolds

The objective of this section is the preparation of 4-deoxy carbohydrates with a 6,8-dioxabicyclo[3.2.1]octane skeleton by applying this 1,5-HAT–S–T rearrangement sequence to C-glycosyl compounds of a C-(α-d,l-glycopyranosyl)methanol general structure, and the results are included in Tables 5 and 6. The sequence was first attempted on the C-(4-O-acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-glucopyranosyl)N-methoxyphthalimide (16) model. In this compound, the glucopyranosyl ring adopts preferentially a ⁴C₁ chair conformation, and thus, the initial 1,5-HAT reaction should be favored (see Table S2 in the SI). However, the tin hydride conditions led to a mixture of four compounds, in which the desired bicycle 45 was isolated as a minor product. The other compounds were the unstable olefin 46 formed presumably by β-(acyloxy)alkyl fragmentation, and 47 and 48 generated by the premature reduction of intermediate radicals (Table 5, entry 1).

Table 5. 1,5-HAT–S–T Sequence in C-(α-d-Glcp)- and C-(α-d-Galp)N-methoxyphthalimides 16–21^a.

^aReagents and conditions: method A: n-Bu₃SnH (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method C: TTMSS (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method D: n-Bu₃SnD (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method E: n-Bu₃SnD (1 equiv), BF₃•Et₂O (0.2 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method F: Hantzsch ester (1.1 equiv), fac-Ir(ppy)₃ (0.01 equiv), THF (0.007 M), rt, blue LED; and method G: Hantzsch ester (0.37 equiv/h), fac-Ir(ppy)₃ (0.01 equiv), THF (0.007 M), rt, blue LED.

^bValues in parentheses are isolate yields; deuterium incorporation (²H/¹H) is included in partially labeled compounds.

Table 6. 1,5-HAT–S–T Sequence in C-(α-l-Fucp)- and C-(α-l-Rhap)N-methoxyphthalimides 22–24^a.

^aReagents and conditions: method A: n-Bu₃SnH (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method C: TTMSS (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method D: n-Bu₃SnD (1 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method E: n-Bu₃SnD (1 equiv), BF₃•Et₂O (0.2 equiv), AIBN (0.1 equiv), PhCH₃ (0.013 M), reflux; method F: Hantzsch ester (1.1 equiv), fac-Ir(ppy)₃ (0.01 equiv), THF (0.007 M), rt, blue LED; and method G: Hantzsch ester (0.37 equiv/h), fac-Ir(ppy)₃ (0.01 equiv), THF (0.007 M), rt, blue LED.

^bValues in parentheses are isolate yields; deuterium incorporation (²H/¹H) is included in partially labeled compounds.

The structural and stereochemical assignment of these compounds rests on spectroscopic and analytical data. Conformational evidence was obtained by extracting the ring J-coupling from a simulated spectrum (see Table S7 in the SI). In addition, the long-range couplings ⁴J_2,1’ (1.1 Hz, calcd 1.1 Hz)⁴⁸ observed in the spectrum of 45 and ⁴J_2,4 (1.2 Hz, calcd 1.2 Hz)⁴⁸ in 47 confirms the ⁴C₁ and ¹C₄ conformations, respectively, for the sugar rings (see Table S4 in the SI). Therefore, the main product 47 was assigned an l-Ido structure by the inversion of configuration at C5. Using TTMSS or n-Bu₃SnD as reductants did not significantly improve the yield of the bicycle 45 but markedly increased the formation of the olefin 46 (Table 5, entries 2 and 3). As expected, the best yield was achieved by adding Lewis acid; [4-²H]45 (39%; ²H/¹H, 2.9:1; 4R/4S, 1:1.2) was formed with a high deuterium content but low stereoselectivity (Table 5, entry 4).

As shown in Table 5 (entries 5–8), we need better LGs for the sequence of reactions to reach the end. In these experiments, the starting 4-O-diphenoxyphosphoryl 17 and 4-O-tosyl-phthalimide 18 were exclusively transformed into 45 or [4-²H]45 and no prereduction or β-fragmentation byproducts were detected. Under photoredox catalysis conditions, tosyl derivative 18 gave the bicycle 45 in poor yield, which could be substantially enhanced by adding the Hantzsch ester slowly via a syringe pump (Table 5, entries 9 and 10).

The reaction of the models C-(6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-galactopyranosyl)N-methoxyphthalimide (20 and 21) was then examined, and the results are presented in Table 5. Under the n-Bu₃SnH(D) conditions and irrespective of whether the starting phthalimide was 20 or 21, no products with the 6,8-dioxabicyclo[3.2.1]octane skeleton were detected (Table 5, entries 11, 12, 15, and 17). In these experiments, the only relevant products isolated were olefin 46 and the l-altrose derivative 50, both generated by the radical quenching at C5 prior to the S–T rearrangement. Best results were ultimately attained using n-Bu₃SnD under the Lewis acid catalyst, with compounds [4-²H]45 (41%; ²H/¹H, 2.8:1; 4R/4S, 1:1.2) and [OCH₂-²H]52 being obtained (Table 5, entry 18). Analogously to the reaction of 16, [4-²H]45 was formed with a high deuterium incorporation at C4 but with a low stereoselectivity (Table 5, compare entries 4 and 18). The incorporation of deuterium in [OCH₂-²H]52 (²H/¹H, 1.1:1) indicates a competitive abstraction of the H5 and the methoxyl group at C2 initiated by the alkoxyl radical through 1,5-HAT and 1,6-HAT processes, respectively. As would be expected, in this d-galactose model 21, which is less prone to undergo the 1,2-(ester)alkyl radical migration, the photoredox catalytic reaction gave only the prereduced alcohol 52, with compound 45 being undetectable by ¹H NMR (Table 5, entries 19 and 20).

A propagation cycle for the acetyl and diphenoxyphosphoryl (α-d-Galp)methan-1-O-yl radical chain reactions, employing tin deuteride as the reductant, is shown in Scheme 3. The alkoxyl radical (I) initiated two competitive abstraction processes: 1,5-HAT of the 5H and 1,6-HAT of one hydrogen of the methoxyl group at C2. The radical II leads to (OCH₂-²H)52, whereas the radical at C5 (III) may be stabilized by three different mechanisms: reduction with inversion of configuration giving rise to l-altrose derivative (5-²H)50 (path a), radical β-fragmentation of the LG that can explain the formation of olefin 46 and the unlabeled 45 (path b),⁴⁵ or continuing the sequence by the radical–ionic mechanism that finally provided (4-²H)45 through the cine cyclization step (path c).

Scheme 3. Propagation Cycle of C-(α-d-Galp)methan-1-O-yl Radicals.

The prereduction of the alkoxyl radical and the initiation and termination steps are omitted for clarity.

A phthalimide precursor 19 having two plausible LGs at C4 and C6 was also included in this study (Table 5, entry 21). Since the endocyclic alkene radical cation intermediate should be more stable than the exocyclic alternative, it is not surprising that we only obtained the 4-deoxy-bicycle 53 by C4-OPO(OPh)₂ migration. This product was accompanied by d-glucitol derivative 54 as a result of the competitive β-fragmentation of the primary alkoxyl radical, which had not previously been observed in other members of this series.,^50c53

Examples with l-sugar frameworks such as α-l-Fucp (23 and 24) and α-l-Rhap (22) have also been accomplished, and the results are summarized in Table 6. Since α-l-Fucp and α-d-Galp have a pseudoenantiomeric relationship, an analogous reaction pattern could be expected. Indeed, the results obtained for the l-Fucp derivatives (23 and 24) are quite similar to those observed for the previously studied d-Galp phthalimides 20 and 21 (compare Table 5, entries 11–20 with Table 6, entries 1–11). Thus, neither the acetyl 23 nor diphenoxyphosphoryl 24 precursor gave the desired 6,8-dioxabicyclic compound when submitted to the n-Bu₃SnH(D)/AIBN conditions in the absence of activating additives (Table 6, entries 1, 2, 6, and 8). In both cases, olefin 56 was the main product with a yield that reached a maximum of 70% using phosphatoxy as LG (Table 6, entry 6).

In the reaction of acetylphthalimide 23, the olefin 56 was always accompanied by small amounts of 57 with an inverted 6-deoxy-d-altrose structure (Table 6, entries 1–5). The conversion of phthalimides 23 and 24 into 6,8-dioxabicyclic compound [4-²H]55 was only possible in the presence of a catalytic amount of BF₃•Et₂O (Table 6, entries 3 and 9). Under these conditions, a new anhydro-alditol 3-O-acetyl-2,6-anhydro-1-deoxy-4,5-di-O-methyl-d-(6-²H)galactitol [(1-²H)60] was also isolated in a very low yield (3%), probably generated by the β-fragmentation of the alkoxyl radical at the beginning of the sequence (not shown in Table 6, entry 3). Parallel to what occurred for the d-Galp derivatives 20 and 21, surprisingly, under photoredox conditions, the acetyl precursor 23 afforded the 6,8-dioxabicyclo 55 although in low yields, while the diphenoxyphosphoryl precursor 24 yielded exclusively the reduced alcohol 59 (compare Table 6, entries 4, 5, 10, and 11 with Table 5, entries 13, 14, 19, and 20).

The phthalimides derived from α-l-Rhap22 and α-d-Glcp 17 have a very similar stereochemical arrangement to the atoms involved in the radical sequence, and consequently, an analogous behavior should be expected (compare Table 5, entries 5 and 6 with Table 6, entries 12 and 14). Indeed, the phthalimide 22 afforded exclusively the 6,8-dioxabicyclo 61 in good yield not only with tin hydride but also employing TTMSS or under the photoredox conditions.

Conclusions

In summary, the fate of the 3-C-(α,β-d,l-glycopyranosyl)1-propan-O-yl radical moves through the C-glycosyl skeleton by a 1,5-HAT–S–T rearrangement radical/polar sequence giving 1,4-anhydro-5-deoxy-non-4-ulopyranoses with a 10-deoxy-1,6-dioxaspiro[4.5]decane structure.

The reaction under the tin hydride conditions appears to be reasonably independent of the axial or equatorial configuration of the abstractable 1H but is highly influenced by the nature and stereochemistry of the LGs (2-acetoxy or 2-phosphatoxy) used in the S–T rearrangement at the end of the sequence.³⁹ Thus, the 2-phosphatoxy LG in an equatorial position as in 3-C-(2-O-diphenoxyphosphoryl-α,β-d-Glcp)1-propoxyphthalimides 2 and 4 was found to provide the best results (Table 1, entries 5–7 and 12–14). With a poorer 2-acetoxy LG axially disposed as in C-(2-O-acetyl-α,β-d-Manp)1-propoxyphthalimides 5 and 7, the sequence did not reach the end and only the prereduced compound 29β was obtained (Table 2, entries 1, 2, and 7–10). In the two intermediate situations—equatorial 2-acetoxy phthalimides 1 and 3 (Table 1, entries 1–4 and 8–11) and axial 2-diphenoxyphosphoryl phthalimides 6 and 8 (Table 2, entries 3–6 and 12–17)—the spirocycle 25 is formed in significant amounts, indicating that the low migratory capacity of the LG can be compensated by favorable stereochemical effects and vice versa. A comparison of the best results obtained with the different LGs has been summarized in Table S9 at the SI.

Some other interesting facts can be culled from the data described in Tables 1 and 2. First, an expected KIE was observed during the formation of 25, with the yield increasing significantly in most cases when deuteride was used instead of hydride donors (e.g., Table 1, compare entries 8 and 11; see also Table S9 in the SI). The sequence yield was also dramatically improved by complexation with BF₃•Et₂O (Table 2, compare entries 10 and 11).

All these observations are in excellent agreement with experimental results obtained in the application of this methodology to C-glycopyranosyl models for the synthesis of either 10-deoxy-1,6-dioxaspiro[4.5]decane (Tables 1–3) or 4-deoxy-6,8-dioxabicyclo[3.2.1]octane frameworks (Tables 5–6). For example, 3-C-(α-l-Fucp)1-propoxyphthalimides 9 and 10 with the pyranosyl ring in a ¹C₄ conformation and the 2-acetoxy and 2-phosphatoxy LGs equatorially disposed afforded the spiroketal 31 in good yield (Table 3, entries 1, 2 and 5, 6). Nevertheless, C-(α-d-Galp)N-methoxyphthalimides 20 and 21 with the pyranosyl ring in a ⁴C₁ conformation and the 4-acetoxy and 4-phosphatoxy LGs axially oriented did not give the expected bicyclic ketal 45, which was achieved only after the addition of BF₃•Et₂O to the reaction media, as evidenced in the case of 21 (Table 5, entry 18). Also in this line, C-(α-l-Rhap)N-methoxyphthalimide 22 (¹C₄, 4-phosphatoxy equatorially positioned) smoothly led to the desired compound 61 (Table 6, entries 12–15), whereas C-(α-l-Fucp)N-methoxyphthalimides 23 and 24 (¹C₄, axial LGs) reacted only under acid catalysis (Table 6, entries 3 and 9).

In the reaction of C-(d,l-Glyp)N-methoxyphthalimides, a new olefin with a C-(hex-4-enopyranosyl)methanol structure was formed (Tables 5 and 6), appearing exclusively when the S–T rearrangement is unfavored: with the 4-acetoxy group in the equatorial or axial disposition (compounds 16, 20, and 23; 4–31%) or with the 4-phosphatoxy group axially oriented (compounds 21 and 24; 44–70%). It is not detected in favored S–T rearrangements (4-phosphatoxy or 4-p-toluenesulfonyloxy equatorial) (compounds 17, 18, and 22). Presumably due to the highly strained dioxabicyclo[3.2.1]octane system, a pure radical β-(ester)alkyl fragmentation competes, in some cases very favorably, with a radical-polar β-(ester)alkyl shift mechanism.

The results observed when the reaction is applied to d-pentoses deserve special comments (Tables 3 and 4). With 3-C-(2-O-diphenoxyphosphoryl-α,β-d-Arap)1-propoxyphthalimides 11 and 12, the reaction behaved analogously and the expected spiroketals 37 and 38 were, respectively, formed in similar yields (Table 3, entries 7–11). Notwithstanding, some differences with these trends are observed during the reaction of d-pentofuranosyl substrates. The reaction of 3-C-(2-acetyl-α-d-Ribf)1-propoxyphthalimide 13 proceeds exclusively in the presence of BF₃•Et₂O and the use of a better LG is necessary, as observed in compounds 14 and 15 (Table 4, entries 5–11).

In these more flexible five-membered rings, the configuration of the LGs does not appear to be as important. A pseudo-rotational analysis of compounds 13, 14, and 15 shows that the most populated conformers appear at phase angles of P = 354–9° (³T₂) in the northern region of the pseudo-rotational itinerary, leaving the LG in a pseudo-axial configuration (see Table S8 in the SI for details).

When the sequences were initiated by visible light photocatalysis, low yields were observed in all 3-C-(α,β-d,l-Glyp)1-propoxyphthalimides, which were in general lower than those obtained with tin hydride (Tables 2 and 3, methods F and G). The spirocycles were always accompanied by high percentages of prereduced products. A similar behavior was observed in most cases of C-(d,l-Glyp)N-methoxyphthalimides. Thus, in the reaction of 21, no traces of products resulting from the 1,5-HAT could be detected, with the prereduced alcohol 52 being formed exclusively (Table 5, entries 19 and 20). This means that, under these conditions, the six-membered TS of the 1,5-HAT cannot be reached probably due to conformational restrictions promoted by the bulky axially oriented diphenoxyphosphatoxy group. Paradoxically, with a poorer 2-acetoxy LG axially disposed as in C-(4-O-acetyl-α-d-Galp)N-methoxyphthalimide 20, the [3.2.1]bicyclic 45 and the inverted l-altro derivative 50 were obtained in a 46% combined yield (Table 5, entries 13 and 14). This is presumably due to the smaller steric demands of the acetoxy group. The same occurred with C-(α-l-Fucp)N-methoxyphthalimides 23 and 24 with which 20 and 21 present a pseudoenantiomeric relationship (Table 6, entries 4, 5 and 10, 11). We have also noted that, under these photoredox conditions, no 4-enopyranosyl olefins (i.e., 46 or 56) were detected (Tables 5–6, methods F and G).

In the best of situations, C-(4-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-l-Rhap)N-methoxyphthalimide (22) (¹C₄, phosphatoxy equatorial) with the Hantzsch ester introduced slowly by a syringe pump, the bicycle 61 is produced in a yield (61%) comparable to that obtained with n-Bu₃SnD/BF₃•Et₂O (Table 6, compare entries 15 and 17). These photocatalyzed reactions, carried out at room temperature, appear to be strongly influenced by the conformational equilibrium of the pyranosyl ring. However, under the tin hydride conditions (refluxing toluene, 110 °C), the TS required for the HAT reaction can be more readily attained.

Preparation of 3-C-(Glycopyranosyl)1-propanol and 3-C-(Glycofuranosyl)1-propanol Models

C-Glycosyl compounds of the 3-C-(α,β-d,l-glycopyranosyl)1-propene type 62, 65, 68, 71, and 75 were synthesized starting from perbenzylated d-glucose, d-mannose, or l-fucose, as required in each case, according to the procedure reported by Nicotra et al. (Scheme 4).⁵⁴ Otherwise, for the d-arabinopyranose series, the allylation of 78 with allyltrimethylsilane and BF₃•Et₂O gave an inseparable anomeric mixture of allyl derivatives in 69% yield. The saponification of the acetyl groups and the selective acetal protection by treatment overnight with PhCH(OMe)₂ and CSA gave access to β- and α-phenyl benzylidene substituted products as a mixture of anomers 79 (β/α, 3:1) and 80 (β/α, 3.5:1) with a free hydroxyl group at C2. Next, oxidative hydroboration of all the allyl compounds mentioned above gave efficiently the corresponding diols 63, 66, 69, 72, 76, and 81, whose primary hydroxyl groups were converted selectively to 3-C-(α,β-d,l-glycopyranosyl)N-propoxyphthalimides by the reaction with N-hydroxyphthalimide via Mitsunobu condensation yielding 64, 67, 70, 73, and 77.⁵⁵ There only remains the subsequent protection of the free secondary hydroxyl group as a good LG. We thus prepared the acetyl derivatives 1, 3, 5, 7, and 9 and the phenyl phosphates 2, 4, 6, 8, 10, and 11. Finally, acid hydrolysis of the benzylidene acetal in the diastereoisomeric mixture 11 provides, after chromatographic purification, the pure major β-diastereomer 12.

In the furanose series, we prepared the corresponding allyl ribose derivative 82 following a similar strategy to that described before for the d-arabinopyranose model (Scheme 5).⁵⁶ Saponification of the acetyl groups and treatment of the corresponding triol with DPSCl and imidazole in dichloromethane at 0 °C produced the diprotected product 83 in 36% yield together with the diol 84 obtained in 40% yield.^13,57 On the other hand, the reaction of 82 with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in dry pyridine afforded the monoalcohol 86 in 69% yield. Once again, oxidative hydroboration of 83 and 86 gave the corresponding diols 85 and 87. The conversion of the primary alcohol to an N-alkoxyphthalimide and the introduction of an LG at C2 afforded the required models: the acetate 13, triflate 14, and phenyl phosphate 15.

Preparation of C-(Glycopyranosyl)methanol Models

The synthesis of 6,8-dioxabicyclo[3.2.1]heptane scaffolds commenced with the preparation of C-(4-O-acetyl-α-d,l-glycopyranosyl)allenes 91, 98, 101, 102, and 107 (Scheme 6). To achieve this with high α-diastereoselectivity, we employed the ultrasound-assisted C-glycosylation described by Murphy et al. using propargyl trimethylsilane and a Lewis acid catalyst.⁵⁸ Next, LG was interchanged from OAc to PO(OPh)₂, yielding 92 and 99, and to the tosyl group, giving access to 93, by saponification of the acetyl group and treatment with the corresponding acid chloride in basic media. Subsequent reductive ozonolysis afforded the C-(α-glycopyranosyl)methanol derivatives 48, 94, 49, 51, and 52 in good yields. Product 48 was also used as a precursor to prepare a diphosphate substrate 95 to analyze whether competitive migrations of the LGs at C4 and C6 could occur. First, it was necessary to protect the primary C1’-alcohol as a tetrahydropyranyl (THP) ether; then removal of both the silyl and the acyl protectors gave a diol, which was transformed to a diphosphate by treatment with ClPO(OPh)₂ in pyridine overnight. Acid hydrolysis of the THP protector afforded 95 in a 37% overall yield (four-step). Finally, Mitsunobu condensation of all the primary alcohols mentioned above with N-hydroxyphthalimide yielded C-(α-glycopyranosyl)N-methoxyphthalimide derivatives 16, 17, 18, 19, 20, and 21 in good to excellent yields.

In the case of the l-rhamnose 101 and l-fucose 107 derivatives, it was found necessary to hydrolyze the acetyl groups at C2, C3, and C4 to protect selectively the C2 and C3 hydroxyl groups as cyclic acetals to enable the ulterior introduction of the LG at C4. Once the isopropylidene group was introduced for the l-rhamnose derivative, benzylation of the free alcohol at C4 afforded 103 in 54% yield. Acid hydrolysis of the transitory acetal assembly, methylation of both C2 and C3 hydroxyl groups, and reductive ozonolysis gave monoalcohol 104 in 45% overall yield. Afterward, palladium-catalyzed hydrogenolysis of the benzyl protective group gave the corresponding diol that was subsequently transformed into the N-alkoxyphthalimide 105 in 57% yield. The corresponding phenyl phosphate 22 was obtained efficiently after 2 h by treatment with ClPO(OPh)₂ and DMAP at room temperature in dichloromethane.

For the l-fucose derivative, butane 2,3-bisacetal protection⁵⁹ was selected to obtain 108 in 65% yield. Next, a similar strategy as described for the previous model was employed to afford monoalcohol 109 in 43% overall yield. Transient protection of the primary alcohol as a DPS ether allows the hydrogenolysis of the benzyl ether and the introduction of the LG at C4. Therefore, the formation of the acetate or phenyl phosphate followed by DPS removal (TBAF) allowed the generation of 58 and 59 in good overall yields. The conversion of the corresponding primary alcohols to N-alkoxyphthalimides occurred in 51% yield for both substrates to generate 23 and 24, respectively.

Experimental Section

General Information

Commercially available reagents and solvents were analytical grade or were purified by standard procedures prior to use. Solvents for starting material preparation and radical reactions were dried before use. The spray reagents for TLC analysis were conducted with 0.5% vanillin in H₂SO₄–EtOH (4:1) or, in some specific cases, with the Pancaldi reagent {(NH₄)₆MoO₄, Ce(SO₄)₂, H₂SO₄, H₂O}⁶⁰ and further heating until the development of color. Melting points were determined with a hot-stage apparatus. Optical rotations were measured at the sodium line at the ambient temperature in CHCl₃ solutions. IR spectra were measured as thin films on CHCl₃ solutions. NMR spectra were determined at 500 or 400 MHz for ¹H and at 125.7 or 100 MHz for ¹³C{¹H} in CDCl₃ or C₆D₆ as stated. The chemical shifts are given in parts per million (ppm) relative to TMS at δ 0.00 ppm or to residual CDCl₃ at δ 7.26 ppm for proton spectra and relative to CDCl₃ at δ 77.00 ppm for carbon spectra. NMR spectra were assigned with the aid of 1D and 2D techniques, including ¹³C DEPT-135, COSY, HSQC, HMBC, and NOESY. The DAISY program as implemented in the TopSpin 4.0.6 software package was used for the simulation of ¹H NMR spectra. Low- and high-resolution mass spectra were recorded by using an electrospray (ESI⁺) and TOF analyzer. Flash column chromatography was performed on a Merck silica gel 60 PF (0.063–0.2 mm). For the chromatography of the radical reactions with n-Bu₃SnH or n-Bu₃SnD, 10% KF was added and mixed with the silica gel. Circular layers of 1 and 2 mm of the Merck silica gel 60 PF₂₅₄ were used on a Chromatotron for centrifugally assisted chromatography. HPLC separations were undertaken using a semipreparative (10 × 250 mm) Ascentis Si normal-phase column. An ultrasonic bath was used (2510E-DTH, Branson) for the synthesis of the allene precursors and for the deoxygenation of the THF for the photocatalytic reactions. Photochemical reactions were carried out with 15 W blue LEDs (468 nm peak wavelength, 25 nm spectral half-wave width, composed of 15 LED units each with 1 W, 3 V, 300 mA, 5 cm distance from the light source to the irradiation vessel). For convenience, the atom-numbering system used along this section and in the assignments of the Experimental Section corresponds to the one depicted in structures of the schemes and tables, although an IUPAC systematic nomenclature has been used throughout this paper. The IUPAC nomenclature for deuterated carbohydrates (2-Carb-16.6, with the parentheses indicating substitution and square brackets for partial labeling) has been used throughout the manuscript.

General Methods for Radical and Photoredox Reactions (Tables 1–6)

Method A: Fast Addition of n-Bu₃SnH

A solution of the phthalimide (1 mmol) in dry toluene (75 mL) was treated with n-Bu₃SnH (269 μL, 1 mmol) and AIBN (16.4 mg, 0.1 mmol) and heated under reflux. Every hour, the same quantity of AIBN was added. In some cases, a supplementary addition of n-Bu₃SnH (269 μL, 1 mmol) was required as indicated. When all the starting material was consumed, the reaction mixture was directly poured into a column chromatography on a silica gel with 10% KF (hexanes to hexanes–EtOAc) to give the corresponding products.

Method B: Slow Addition of n-Bu₃SnH (1 equiv/h)

A solution of the phthalimide (1 mmol) in dry toluene (75 mL) was treated with AIBN (16.4 mg, 0.1 mmol), and n-Bu₃SnH (269 μL, 1 mmol) was dropwise added during 1 h by means of a syringe pump under reflux. Every hour, the same quantity of AIBN was added. In some cases, a supplementary addition of n-Bu₃SnH (269 μL, 1 mmol) was required as indicated. When all the starting material was consumed, the reaction mixture was directly poured into a column chromatography on a silica gel with 10% KF (hexanes to hexanes–EtOAc) to give the corresponding products.

Method C: Fast Addition of TTMSS

A solution of the phthalimide (1 mmol) in dry toluene (75 mL) was treated with AIBN (16.4 mg, 0.1 mmol) and TTMSS (308.5 μL, 1 mmol) and heated under reflux. Every hour, the same quantity of AIBN was added. In some cases, a supplementary addition of TTMSS (308.5 μL, 1 mmol) was required as indicated. When all the starting material was consumed, the reaction mixture was evaporated and purified by column chromatography (hexanes–EtOAc) to give the corresponding products.

Method D: Fast Addition of n-Bu₃SnD

A solution of the phthalimide (1 mmol) in dry toluene (75 mL) was treated with n-Bu₃SnD (270.4 μL, 1 mmol) and AIBN (16.4 mg, 0.1 mmol) and heated under reflux. Every hour, the same quantity of AIBN was added. In some cases, a supplementary addition of n-Bu₃SnD (270.4 μL, 1 mmol) was required as indicated. When all the starting material was consumed, the reaction mixture was directly poured into a column chromatography on a silica gel with 10% KF (hexanes to hexanes–EtOAc) to give the corresponding products.

Method E: Fast Addition of n-Bu₃SnD and BF₃•Et₂O

A solution of the phthalimide (1 mmol) in dry toluene (75 mL) was treated with n-Bu₃SnD (270.4 μL, 1 mmol), BF₃•Et₂O (24.7 μL, 0.2 mmol), and AIBN (16.4 mg, 0.11 mmol) and heated at 100 °C. Every hour, the same quantity of AIBN was added. In some cases, a supplementary addition of n-Bu₃SnD (270.4 μL, 1 mmol) and BF₃•Et₂O (24.7 μL, 0.2 mmol) was required as indicated. When all the starting material was consumed, the reaction mixture was directly poured into a column chromatography on a silica gel with 10% KF (hexanes to hexanes–EtOAc) to give the corresponding products.

Method F: Photoredox Conditions

A deoxygenated solution of the phthalimide (1 mmol), Hantzsch ester (278.6 mg, 1.1 mmol), and fac-Ir(ppy)₃ (6.5 mg, 0.01 mmol) in dry THF (148.7 mL) was placed in a Schlenk tube under nitrogen and irradiated with blue LEDs at room temperature. The reaction mixture was concentrated and purified directly by chromatotron (hexanes–EtOAc) to give the corresponding products.

Method G: Photoredox Conditions with Slow Addition of Hantzsch Ester

A deoxygenated solution of the phthalimide (1 mmol) and fac-Ir(ppy)₃ (6.5 mg, 0.01 mmol) in dry THF (116 mL) was placed in a Schlenk tube under nitrogen and irradiated with blue LEDs at room temperature. A solution of Hantzsch ester (279.1 mg, 1.1 mmol) in dry THF (34.9 mL) was then slowly added with a syringe pump over a period of 3 h. The reaction mixture was concentrated and purified directly by chromatotron (hexanes–EtOAc, 8:2 to 1:1) to give the corresponding products.

Synthesis of 10-Deoxy-1,6-dioxaspiro[4.5]decane Structures (Tables 1–3)

Radical Reactions of 1

Method A

Following the general procedure, starting from substrate 1 (62.8 mg, 0.092 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (25 μL, 0.092 mmol) was required. All the starting material was consumed after 3 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave (4S)-1,4-anhydro-6,7,9-tri-O-benzyl-2,3,5-trideoxy-d-arabino-non-4-ulopyranose (25) (18.6 mg, 0.039 mmol, 43%) as an amorphous solid, 3-C-(2-O-acetyl-3,4,6-tri-O-benzyl-β-d-glucopyranosyl)1-propanol (26β) (6.9 mg, 0.013 mmol, 14%) as a colorless oil, and 3-C-(2-O-acetyl-3,4,6-tri-O-benzyl-α-d-glucopyranosyl)1-propanol (26α) (4.1 mg, 0.008 mmol, 8%) as an amorphous solid. Compound 25: [α]_D = +40.0 (c = 0.18, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.34–7.18 (m, 15H, Ar), 4.89 (d, J = 11.1 Hz, 1H, OBn), 4.66 (d, J = 11.7 Hz, 1H, OBn), 4.62 (d, J = 11.7 Hz, 1H, OBn), 4.61 (d, J = 12.3 Hz, 1H, OBn), 4.54 (d, J = 11.0 Hz, 1H, OBn), 4.51 (d, J = 12.3 Hz, 1H, OBn), 3.990 (ddd, J = 11.5, 8.9, 5.1 Hz, 1H, 3-H), 3.89 (ddd, J = 8.2, 8.2, 5.4 Hz, 1H, 3’-H_b), 3.83 (ddd, J = 8.2, 8.2, 6.3 Hz, 1H, 3’-H_a), 3.79 (ddd, J = 9.9, 4.3, 1.9 Hz, 1H, 5-H), 3.74 (dd, J = 10.8, 4.3 Hz, 1H, 6-H_b), 3.64 (dd, J = 10.8, 1.9 Hz, 1H, 6-H_a), 3.57 (dd, J = 9.9, 8.9 Hz, 1H, 4-H), 2.222 (dd, J = 12.7, 5.1 Hz, 1H, 2-H_b), 2.12–2.00 (m, 2H, 1’-H_b, 2’-H_b), 1.872 (dd, J = 12.7, 11.5 Hz, 1H, 2-H_a), 1.85 (m, 1H, 2’-H_a), 1.76 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 138.9 (2 × C, Ar), 138.5 (C, Ar), 128.34 (2 × CH, Ar), 128.28 (2 × CH, Ar), 128.2 (2 × CH, Ar), 127.76 (2 × CH, Ar), 127.74 (2 × CH, Ar), 127.6 (2 × CH, Ar), 127.5 (2 × CH, Ar), 127.4, (CH, Ar), 106.33 (C, C-1), 79.2 (CH, C-4), 78.51 (CH, C-3), 74.7 (CH₂, OBn), 73.3 (CH₂, OBn), 71.8 (CH₂, OBn), 71.8 (CH, C-5), 69.4 (CH₂, C-6), 67.3 (CH₂, C-3’), 38.62 (CH₂, C-2), 37.2 (CH₂, C-1’), 23.5 ppm (CH₂, C-2’). IR (CHCl₃): ν = 3009, 2939, 1456, 1089 cm^–1. MS (ESI) m/z (%) = 497 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₀H₃₄NaO₅ 497.2304; found 497.2303. Anal. calcd for C₃₀H₃₄O₅: C, 75.92; H, 7.12. Found: C, 76.07; H, 7.21. Compound 26β: [α]_D = +12.3 (c = 0.43, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.34–7.15 (m, 15H, Ar), 4.887 (dd, J = 9.3, 9.3 Hz, 1H, 2-H), 4.81 (d, J = 11.4 Hz, 1H, OBn), 4.77 (d, J = 10.9 Hz, 1H, OBn), 4.65 (d, J = 11.4 Hz, 1H, OBn), 4.59 (d, J = 12.2 Hz, 1H, OBn), 4.53 (d, J = 12.2 Hz, 1H, OBn), 4.52 (d, J = 10.6 Hz, 1H, OBn), 3.68 (dd, J = 10.9, 1.9 Hz, 1H, 6-H_b), 3.66–3.59 (m, 5H, 3’-H₂, 3-H, 4-H, 6-H_a), 3.46 (m, 1H, 5-H), 3.34 (ddd, J = 9.8, 9.8, 2.4 Hz, 1H, 1-H), 1.94 (s, 3H, OAc), 1.75–1.61 (m, 3H, 1’-H_b, 2’-H₂), 1.509 ppm (m, 1H, 1’-H_a), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 169.9 (C, OAc), 138.4 (C, Ar), 138.1 (C, Ar), 138.0 (C, Ar), 128.42 (2 × CH, Ar), 128.41 (2 × CH, Ar), 128.37 (2 × CH, Ar), 128.0 (2 × CH, Ar), 127.8 (3 × CH, Ar), 127.70 (2 × CH, Ar), 127.67 (CH, Ar), 127.6 (CH, Ar), 84.7 (CH, C-3), 79.0 (CH, C-4), 78.5 (CH, C-5), 78.0 (CH, C-1), 75.2 (CH₂, OBn), 75.0 (CH₂, OBn), 73.81 (CH, C-2), 73.5 (CH₂, OBn), 69.1 (CH₂, C-6), 62.7 (CH₂, C-3’), 28.84 (CH₂, C-2’), 28.24 (CH₂, C-1’), 20.9 ppm (CH₃, OAc). IR (CHCl₃): ν = 3430, 3014, 1738, 1229, 1039 cm^–1. MS (ESI) m/z (%) = 557 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₃₈NaO₇ 557.2515; found 557.2513. Anal. calcd for C₃₂H₃₈O₇: C, 71.89; H, 7.16. Found: C, 71.86; H, 7.37. Compound 26α: [α]_D = +41.4 (c = 0.36, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.34–7.14 (m, 15H, Ar), 5.03 (dd, J = 8.5, 5.4 Hz, 1H, 2-H), 4.75 (d, J = 11.7 Hz, 1H, OBn), 4.70 (d, J = 11.0 Hz, 1H, OBn), 4.70 (d, J = 11.0 Hz, 1H, OBn), 4.59 (d, J = 12.0 Hz, 1H, OBn), 4.51 (d, J = 12.0 Hz, 1H, OBn), 4.48 (d, J = 11.1 Hz, 1H, OBn), 4.13 (m, 1H, 1-H), 3.81 (dd, J = 8.2, 8.2 Hz, 1H, 3-H), 3.75 (ddd, J = 8.2, 3.8, 3.8 Hz, 1H, 5-H), 3.71–3.63 (m, 4H, 3’-H₂, 6-H₂), 3.60 (dd, J = 8.2, 8.2 Hz, 1H, 4-H), 1.99 (s, 3H, OAc), 1.87 (br s, 1H, OH), 1.80 (m, 1H, 1’-H_b), 1.70–1.58 (m, 2H, 2’-H₂), 1.51 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 170.0 (C, OAc), 138.3 (C, Ar), 138.0 (2 × C, Ar), 127.6–128.4 (15 × CH, Ar), 79.9 (CH, C-3), 77.5 (CH, C-4), 74.6 (CH₂, OBn), 74.5 (CH₂, OBn), 73.4 (CH₂, OBn), 73.0 (CH, C-2), 72.4 (CH, C-1), 72.0 (CH, C-5), 69.1 (CH₂, C-6), 62.2 (CH₂, C-3’), 28.9 (CH₂, C-2’), 22.5 (CH₂, C-1’), 20.9 ppm (CH₃, OAc). IR (CHCl₃): ν = 3477, 3014, 2942, 1740, 1236, 1100 cm^–1. MS (ESI) m/z (%) = 557 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₃₈NaO₇ 557.2515; found 557.2515. Anal. calcd for C₃₂H₃₈O₇: C, 71.89; H, 7.16. Found: C, 71.57; H, 7.51.

Method B

Following the general procedure, starting from substrate 1 (123.9 mg, 0.18 mmol), after 2 h of reaction, two more equivalents of n-Bu₃SnH (98 μL, 0.36 mmol) added by a syringe pump were required. All the starting material was consumed after 14 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave 25 (43.4 mg, 0.09 mmol, 50%) and 26α (14.1 mg, 0.026 mmol, 15%).

Method C

Following the general procedure, starting from substrate 1 (62.8 mg, 0.092 mmol), after 2 h of reaction, a supplementary addition of TTMSS (28.5 μL, 0.092 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes–EtOAc, 9:1 to 6:4) gave 25 (8.4 mg, 0.018 mmol, 19%) and the reduced product 26α (1.5 mg, 0.003 mmol, 3%).

Method D

Following the general procedure, starting from substrate 1 (94 mg, 0.14 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (37 μL, 0.14 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave (4S)-1,4-anhydro-6,7,9-tri-O-benzyl-2,3,5-trideoxy-d-(5-²H)arabino-non-4-ulopyranose [(2-²H)25] (28.5 mg, 0.060 mmol, 43%, 2β-²H/2α-²H, 7:3) as an amorphous solid, 3-C-(2-O-acetyl-3,4,6-tri-O-benzyl-β-d-(1-²H)glucopyranosyl)1-propanol [(1-²H)26β] (4.8 mg, 0.009 mmol, 6%) as a colorless oil, and the prematurely reduced product 26α (3 mg, 0.006 mmol, 4%). Compound (2-²H)25: ¹H NMR (400 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.35–7.18 (m, 15H, Ar). 4.89 (d, J = 11.1 Hz, 1H, OBn), 4.66 (d, J = 11.7 Hz, 1H, OBn), 4.61 (d, J = 12.3 Hz, 1H, OBn), 4.61 (d, J = 12.3 Hz, 1H, OBn), 4.54 (d, J = 11.0 Hz, 1H, OBn), 4.51 (d, J = 12.3 Hz, 1H, OBn), 3.987 [dd, J = 8.9, 5.1 Hz, 0.7H, 3-H (from 2β-²H)], 3.987 [dd, J = 11.5, 8.9 Hz, 0.3H, 3-H (from 2α-²H)], 3.89 (ddd, J = 8.2, 8.2, 5.3 Hz, 1H, 3’-H_b), 3.83 (ddd, J = 8.2, 8.2, 6.6 Hz, 1H, 3’-H_a), 3.79 (ddd, J = 9.9, 4.2, 1.7 Hz, 1H, 5-H), 3.74 (dd, J = 10.7, 4.2 Hz, 1H, 6-H_b), 3.65 (dd, J = 10.7, 1.7 Hz, 1H, 6-H_a), 3.57 (dd, J = 9.9, 8.9 Hz, 1H, 4-H), 2.200 (d, J = 5.1 Hz, 0.7H, 2α-H), 2.13–1.99 (m, 2H, 1’-H_b, 2’-H_b), 1.86 (m, 1H, 2’-H_a), 1.85 (d, J = 11.5 Hz, 0.3H, 2β-H), 1.74 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 138.9 (2 × C, Ar), 138.5 (C, Ar), 128.33 (2 × CH, Ar), 128.28 (2 × CH, Ar), 128.2 (2 × CH, Ar), 127.76 (2 × CH, Ar), 127.74 (2 × CH, Ar), 127.6 (2 × CH, Ar), 127.5 (2 × CH, Ar), 127.4, (CH, Ar), 106.30 (C, C-1), 79.1 (CH, C-4), 78.50 (CH, C-3), 74.7 (CH₂, OBn), 73.3 (CH₂, OBn), 71.8 (CH₂, OBn), 71.8 (CH, C-5), 69.4 (CH₂, C-6), 67.2 (CH₂, C-3’), 38.26 (CHD, t, J_CD = 19.7 Hz, C-2), 37.1 (CH₂, C-1’), 23.5 ppm (CH₂, C-2’). MS (ESI) m/z (%) = 498 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₀H₃₃²HNaO₅ 498.2367; found 498.2366. Compound (1-²H)26β: ¹H NMR (400 MHz, CDCl₃) δ_H 7.34–7.14 (m, 15H, Ar), 4.881 (d, J = 8.8 Hz, 1H, 2-H), 4.81 (d, J = 11.4 Hz, 1H, OBn), 4.77 (d, J = 10.8 Hz, 1H, OBn), 4.65 (d, J = 11.4 Hz, 1H, OBn), 4.59 (d, J = 12.2 Hz, 1H, OBn), 4.55 (d, J = 10.2 Hz, 1H, OBn), 4.52 (d, J = 10.6 Hz, 1H, OBn), 3.69 (dd, J = 10.7, 1.9 Hz, 1H, 6-H_b), 3.66–3.57 (m, 5H, 3’-H₂, 3-H, 4-H, 6-H_a), 3.46 (m, 1H, 5-H), 1.94 (s, 3H, OAc), 1.75–1.61 (m, 3H, 1’-H_b, 2’-H₂), 1.497 ppm (ddd, J = 13.4, 13.4, 6.4 Hz, 1H, 1’-H_a), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 169.9 (C, OAc), 138.4 (C, Ar), 138.1 (C, Ar), 138.0 (C, Ar), 128.42 (4 × CH, Ar), 128.38 (2 × CH, Ar), 128.0 (2 × CH, Ar), 127.8 (3 × CH, Ar), 127.70 (2 × CH, Ar), 127.67 (CH, Ar), 127.65 (CH, Ar), 84.6 (CH, C-3), 78.9 (CH, C-4), 78.5 (CH, C-5), 75.2 (CH₂, OBn), 75.0 (CH₂, OBn), 73.74 (CH, C-2), 73.5 (CH₂, OBn), 69.1 (CH₂, C-6), 62.7 (CH₂, C-3’), 28.8 (CH₂, C-2’), 28.13 (CH₂, C-1’), 20.9 ppm (CH₃, OAc). MS (ESI) m/z (%) = 558 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₃₇²HNaO₇ 558.2578; found 558.2574.

Radical Reactions of 2

Method A

Following the general procedure, starting from substrate 2 (89.7 mg, 0.10 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (29 μL, 0.11 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave 25 (20.8 mg, 0.044 mmol, 44%) and an inseparable mixture of alcohols (12.8 mg, 0.018 mmol, 16%) that was elucidated by the usual acetylation to obtain 3-C-(3,4,6-tri-O-benzyl-2-O-diphenoxyphosphoryl-β-d-glucopyranosyl)1-propyl acetate (27β) (3.9 mg, 0.005 mmol, 5% from 2) and 3-C-(3,4,6-tri-O-benzyl-2-O-diphenoxyphosphoryl-α-d-glucopyranosyl)1-propyl acetate (27α) (6.1 mg, 0.008 mmol, 7% from 2), both as colorless oils. Compound 27β: [α]_D = +16.2 (c = 0.33, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.36–7.11 (m, 25H, Ar), 4.59 (d, J = 12.3 Hz, 1H, OBn), 4.52 (m, 1H, 2-H), 4.52 (d, J = 12.0 Hz, 1H, OBn), 4.51 (d, J = 12.0 Hz, 1H, OBn), 4.46 (d, J = 12.3 Hz, 1H, OBn), 4.43 (d, J = 12.0 Hz, 1H, OBn), 4.13 (d, J = 12.3 Hz, 1H, OBn), 4.09 (dd, J = 2.5, 2.5 Hz, 1H, 3-H), 4.01–3.92 (m, 3H, 5-H, 3’-H₂), 3.78 (m, 1H, 1-H), 3.68 (dd, J = 10.1, 6.6 Hz, 1H, 6-H_b), 3.54 (dd, J = 10.1, 5.7 Hz, 1H, 6-H_a), 3.35 (br s, 1H, 4-H), 1.98 (s, 3H, OAc), 1.83–1.75 (m, 2H, 1’-H_b, 2’-H_b), 1.65–1.39 ppm (m, 2H, 1’-H_a, 2’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 171.1 (C, OAc), 150.5 (2 × C, Ar), 138.3 (C, Ar), 137.7 (C, Ar), 137.4 (C, Ar), 120.0–129.7 (25 × CH, Ar), 77.2 (CH, C-2), 75.4 (CH, C-5), 74.6 (d, ³J_PC = 6.4 Hz, CH, C-1), 73.4 (CH₂, OBn), 72.3 (CH₂, OBn), 71.7 (CH, C-3 or C-4), 71.6 (CH₂, OBn), 71.5 (CH, C-3 or C-4), 69.8 (CH₂, C-6), 64.3 (CH₂, C-3’), 27.5 (CH₂, C-1’ or C-2’), 24.9 (CH₂, C-1’ or C-2’), 20.9 ppm (CH₃, OAc). IR (CHCl₃): ν = 2927, 1733, 1491, 1027 cm^–1. MS (ESI) m/z (%) = 789 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₄H₄₇NaO₁₀P 789.2805; found 789.2831. Compound 27α: [α]_D = +22.0 (c = 0.30, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.32–7.08 (m, 25H, Ar), 4.82 (d, J = 11.1 Hz, 1H, OBn), 4.79 (ddd, J = 8.3, 5.7 Hz, ³J_PH = 8.3 Hz, 1H, 2-H), 4.74 (d, J = 10.7 Hz, 1H, OBn), 4.73 (d, J = 11.1 Hz, 1H, OBn), 4.60 (d, J = 12.0 Hz, 1H, OBn), 4.46 (d, J = 12.3 Hz, 1H, OBn), 4.45 (d, J = 10.5 Hz, 1H, OBn), 4.15 (m, 1H, 1-H), 4.02 (ddd, J = 10.7, 10.7, 6.3 Hz, 1H, 3’-H_b), 3.98 (ddd, J = 10.8, 10.8, 6.3 Hz, 1H, 3’-H_a), 3.86 (dd, J = 8.6, 8.6 Hz, 1H, 3-H), 3.70–3.60 (m, 4H, 4-H, 5-H, 6-H₂), 2.00 (s, 3H, OAc), 1.77–1.69 (m, 2H, 1’-H_b, 2’-H_b), 1.62–1.49 ppm (m, 2H, 1’-H_a, 2’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 171.1 (C, OAc), 150.5 (2 × C, Ar), 138.0 (C, Ar), 137.9 (C, Ar), 137.8 (C, Ar), 129.8 (2 × CH, Ar), 129.7 (2 × CH, Ar), 128.41 (2 × CH, Ar), 128.37 (2 × CH, Ar), 128.3 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.84 (3 × CH, Ar), 127.78 (2 × CH, Ar), 127.7 (CH, Ar), 127.6 (CH, Ar), 125.5 (CH, Ar), 125.3 (CH, Ar), 120.14 (CH, Ar), 120.10 (CH, Ar), 120.0 (CH, Ar), 119.9 (CH, Ar), 119.9–129.8 (25 × CH, Ar), 80.5 (d, ³J_PC = 6.4 Hz, CH, C-3), 78.4 (d, ³J_PC = 7.4 Hz, CH, C-1), 77.7 (CH, C-2), 75.1 (CH₂, OBn), 74.9 (CH₂, OBn), 73.5 (CH₂, OBn), 73.4 (CH, C-5), 71.5 (CH, C-4), 68.6 (CH₂, C-6), 64.1 (CH₂, C-3’), 24.5 (CH₂, C-1’ or C-2’), 24.5 (CH₂, C-1’ or C-2’), 21.0 ppm (CH₃, OAc). IR (CHCl₃): ν = 3013, 2928, 1730, 1026 cm^–1. MS (ESI) m/z (%) = 789 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₄H₄₇NaO₁₀P 789.2805; found 789.2823.

Method B

Following the general procedure, starting from substrate 2 (56 mg, 0.064 mmol), after 2 h of reaction, two more equivalents of n-Bu₃SnH (35 μL, 0.128 mmol) added by a syringe pump were required. All the starting material was consumed after 11 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave 25 (16.2 mg, 0.034 mmol, 53%).

Method D

Following the general procedure, starting from substrate 2 (66.3 mg, 0.076 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (21 μL, 0.076 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave (2-²H)25 (22.5 mg, 0.047 mmol, 62%) and the inseparable mixture of 3-C-(3,4,6-tri-O-benzyl-2-O-diphenoxyphosphoryl-β-d-(1-²H)glucopyranosyl)1-propanol [(1-²H)28β] and 3-C-(3,4,6-tri-O-benzyl-2-O-diphenoxyphosphoryl-α-d-glucopyranosyl)1-propanol (28α) (11.1 mg, 0.015 mmol, 20%, (1-²H)28β/28α, 1:2.1) as a colorless oil. Compounds (1-²H)28β and 28α: ¹H NMR (500 MHz, CDCl₃, selected resolved signals of (1-²H)28β from the mix spectrum) δ_H 4.74 (d, J = 11.0 Hz, 1H, OBn), 4.74 (d, J = 11.0 Hz, 1H, OBn), 4.59 (d, J = 12.0 Hz, 1H, OBn), 4.532 (d, J = 2.6 Hz, 1H, 2-H), 4.53 (d, J = 12.0 Hz, 1H, OBn), 4.46 (d, J = 11.0 Hz, 1H, OBn), 4.42 (d, J = 11.7 Hz, 1H, OBn), 4.10 (d, J = 12.2 Hz, 1H, OBn), 4.07 (dd, J = 2.6, 2.6 Hz, 1H, 3-H), 3.44 (dd, J = 10.1, 0.0 Hz, 1H, 6-H_a), 3.31 ppm (dd, J = 2.6, 1.0 Hz, 1H, 4-H). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, selected resolved signals of (1-²H)28β from the mix spectrum) δ_C 150.4 (d, ²J_PC = 7.0 Hz, 2 × C, Ar), 138.1 (C, Ar), 137.6 (C, Ar), 137.3 (C, Ar), 80.5 (d, ³J_PC = 6.4 Hz, CH, C-3), 78.55 (d, ²J_PC = 7.4 Hz, CH, C-2), 75.0 (CH, C-5), 73.5 (CH₂, OBn), 72.2 (CH₂, OBn), 71.5 (CH₂, OBn), 71.5 (CH, C-4), 69.8 (CH₂, C-6), 62.5 (CH₂, C-3’), 29.68 (CH₂, C-1’ or C-2’), 28.08 ppm (CH₂, C-1’ or C-2’). ¹H NMR (500 MHz, CDCl₃, selected resolved signals of 28α from the mix spectrum) δ_H 4.80 (d, J = 11.0 Hz, 1H, OBn), 4.770 (ddd, J = 7.6, 4.5 Hz, ³J_PH = 6.3 Hz, 1H, 2-H), 4.71 (d, J = 10.8 Hz, 1H, OBn), 4.58 (d, J = 12.0 Hz, 1H, OBn), 4.48 (d, J = 12.3 Hz, 1H, OBn), 4.44 (d, J = 11.1 Hz, 1H, OBn), 4.23 (ddd, J = 11.4, 5.7, 2.2 Hz, 1-H), 3.85 ppm (dd, J = 8.5, 8.5 Hz, 1H, 3-H). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, selected resolved signals of 28α from the mix spectrum) δ_C 150.5 (d, ²J_PC = 7.0 Hz, 2 × C, Ar), 138.0 (C, Ar), 137.8 (2 × C, Ar), 80.5 (d, ³J_PC = 6.4 Hz, CH, C-3), 78.55 (d, ²J_PC = 7.4 Hz, CH, C-2), 77.8 (CH, C-5), 75.1 (CH₂, OBn), 74.8 (CH₂, OBn), 73.6 (CH, C-1), 73.5 (CH₂, OBn), 71.4 (CH, C-4), 68.8 (CH₂, C-6), 61.8 (CH₂, C-3’), 28.56 (CH₂, C-1’ or C-2’), 20.69 ppm (CH₂, C-1’ or C-2’). IR (CHCl₃): ν = 3490, 3422, 2928, 1550, 1491, 1192 cm^–1. MS (ESI) m/z (%) = 747 (99.6) [M + Na]⁺, 748 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₂H₄₅NaO₉P 747.2699; found 747.2697, [M + Na]⁺ calcd for C₄₂H₄₄²HNaO₉P 748.2762; found 748.2764.

Radical Reactions of 3

Method A

Following the general procedure, starting from substrate 3 (89.2 mg, 0.13 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (36 μL, 0.13 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave 25 (13.9 mg, 0.029 mmol, 23%) and 26β (20.4 mg, 0.038 mmol, 29%).

Method B

Following the general procedure, starting from substrate 3 (110.2 mg, 0.16 mmol), after 2 h of reaction, two more equivalents of n-Bu₃SnH (88 μL, 0.32 mmol) added by a syringe pump over 2 h were required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave 25 (22.4 mg, 0.047 mmol, 30%) and the reduced product 26β (16.4 mg, 0.031 mmol, 19%).

Method C

Following the general procedure, starting from substrate 3 (96.2 mg, 0.14 mmol), after 2 h of reaction, a supplementary addition of TTMSS (66 μL, 0.21 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes–EtOAc, 9:1 to 6:4) gave 25 (10.2 mg, 0.022 mmol, 23%) and the reduced product 26β (3 mg, 0.006 mmol, 4%).

Method D

Following the general procedure, starting from substrate 3 (106.6 mg, 0.16 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (42 μL, 0.16 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave (2-²H)25 (25.2 mg, 0.053 mmol, 33%) and [1-²H]26β (8.3 mg, 0.016 mmol, 10%, ²H/¹H 1:1).

Radical Reactions of 4

Method A

Following the general procedure, starting from substrate 4 (57.3 mg, 0.066 mmol), after 2 h of reaction and again after 4 h, a supplementary addition of n-Bu₃SnH (18 μL, 0.066 mmol) was required. All the starting material was consumed after 6 h. Column chromatography (hexanes to hexanes–EtOAc, 8:2) gave 25 (14.2 mg, 0.030 mmol, 45%).

Method B

Following the general procedure, starting from substrate 4 (53 mg, 0.061 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (16 μL, 0.061 mmol) added by a syringe pump over 1 h was required. All the starting material was consumed after 6 h. Column chromatography (hexanes to hexanes–EtOAc, 8:2) gave 25 (12 mg, 0.025 mmol, 42%).

Method D

Following the general procedure, starting from substrate 4 (75 mg, 0.086 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (23 μL, 0.086 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 8:2) gave (2-²H)25 (22.5 mg, 0.047 mmol, 55%).

Radical Reactions of 5

Method A

Following the general procedure, starting from substrate 5 (40.2 mg, 0.059 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (16 μL, 0.059 mmol) was required. All the starting material was consumed after 7 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave an inseparable mixture of isomers 3-C-(2-O-acetyl-3,4,6-tri-O-benzyl-β-d-mannopyranosyl)1-propanol (29β) and 3-C-(2-O-acetyl-3,4,6-tri-O-benzyl-α-d-mannopyranosyl)1-propanol (29α) (16.1 mg, 0.030 mmol, 51%, 2.3:1) as a colorless oil. Compounds 29β and 29α: ¹H NMR (500 MHz, selected resolved signals of 29β from the mix spectrum) δ_H 5.473 (dd, J = 2.2, 0.0 Hz, 1H, 2-H), 4.85 (d, J = 10.8 Hz, 1H, OBn), 4.74 (d, J = 11.4 Hz, 1H, OBn), 4.61 (d, J = 12.3 Hz, 1H, OBn), 4.54 (d, J = 12.0 Hz, 1H, OBn), 4.50 (d, J = 11.1 Hz, 1H, OBn), 4.49 (d, J = 11.4 Hz, 1H, OBn), 4.48 (d, J = 10.4 Hz, 1H, OBn), 2.17 ppm (s, 3H, OAc). ¹³C{¹H} NMR (100.6 MHz, CDCl₃, selected resolved signals of 29β from the mix spectrum) δ_C 170.9 (C, OAc), 138.3 (C, Ar), 138.2 (C, Ar), 137.8 (C, Ar), 81.9 (CH), 79.3 (CH), 77.2 (CH, C-1), 75.1 (CH₂, OBn), 74.7 (CH), 73.5 (CH₂, OBn), 71.6 (CH₂, OBn), 69.6 (CH₂, C-6), 69.56 (CH, C-2), 62.6 (CH₂, C-3’), 29.5 (CH₂, C-2’), 29.3 (CH₂, C-2’), 28.17 (CH₂, C-1’), 21.0 ppm (CH₃, OAc). ¹H NMR (500 MHz, CDCl₃, selected resolved signals of 29α from the mix spectrum) δ_H 5.245 (dd, J = 2.8, 2.8 Hz, 1H, 2-H), 4.81 (d, J = 11.1 Hz, 1H, OBn), 4.65 (d, J = 11.4 Hz, 1H, OBn), 4.61 (d, J = 12.3 Hz, 1H, OBn), 4.51 (d, J = 11.7 Hz, 1H, OBn), 4.47 (d, J = 11.1 Hz, 1H, OBn), 3.99 (ddd, J = 10.7, 6.6, 3.8 Hz, 1H, 1-H), 3.85 (dd, J = 8.2, 3.2 Hz, 1H, 3-H), 2.13 ppm (s, 3H, OAc). ¹³C{¹H} NMR (100.6 MHz, CDCl₃, selected resolved signals of 29α from the mix spectrum) δ_C 170.6 (C, OAc), 138.3 (C, Ar), 138.2 (C, Ar) 137.8 (C, Ar), 77.7 (CH), 75.3 (CH₂, OBn), 74.8 (CH), 74.7 (CH), 73.5 (CH₂, OBn), 72.8 (CH), 71.9 (CH₂, OBn), 70.9 (CH), 69.4 (CH₂, C-6), 62.0 (CH₂, C-3’), 24.95 (CH₂, C-1’), 21.2 ppm (CH₃, OAc). IR (CHCl₃): ν = 3496, 3014, 2928, 1735, 1238, 1095 cm^–1. MS (ESI) m/z (%) = 557 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₃₈NaO₇ 557.2515; found 557.2515. Anal. calcd for C₃₂H₃₈O₇: C, 71.89; H, 7.16. Found: C, 71.55; H, 7.11.

Method D

Following the general procedure, starting from substrate 5 (30.2 mg, 0.044 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (12 μL, 0.044 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 7:3) gave the mixture of 3-C-(2-O-acetyl-3,4,6-tri-O-benzyl-β-d-(1-²H)mannopyranosyl)1-propanol [(1-²H)29β] and 29α (14.4 mg, 0.027 mmol, 61%, ²H/¹H 1.8:1) as a colorless oil. Compounds (1-²H)29β and 29α: ¹H NMR (500 MHz, CDCl₃, selected resolved signals of (1-²H)29β from the mix spectrum) δ_H 4.74 (d, J = 11.0 Hz, 1H, OBn), 4.74 (d, J = 11.0 Hz, 1H, OBn), 4.59 (d, J = 12.0 Hz, 1H, OBn), 4.532 (d, J = 2.6 Hz, 1H, 2-H), 4.53 (d, J = 12.0 Hz, 1H, OBn), 4.46 (d, J = 11.0 Hz, 1H, OBn), 4.42 (d, J = 11.7 Hz, 1H, OBn), 4.10 (d, J = 12.2 Hz, 1H, OBn), 4.07 (dd, J = 2.6, 2.6 Hz, 1H, 3-H), 3.44 (dd, J = 10.1, 0.0 Hz, 1H, 6-H_a), 3.31 ppm (dd, J = 2.6, 1.0 Hz, 1H, 4-H). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, selected resolved signals of (1-²H)29β from the mix spectrum) δ_C 150.4 (d, ²J_PC = 7.0 Hz, 2 × C, Ar), 138.1 (C, Ar), 137.6 (C, Ar), 137.3 (C, Ar), 80.5 (d, ³J_PC = 6.4 Hz, CH, C-3), 78.55 (d, ²J_PC = 7.4 Hz, CH, C-2), 75.0 (CH, C-5), 73.5 (CH₂, OBn), 72.2 (CH₂, OBn), 71.5 (CH₂, OBn), 71.5 (CH, C-4), 69.8 (CH₂, C-6), 62.5 (CH₂, C-3’), 29.68 (CH₂, C-1’ or C-2’), 28.08 ppm (CH₂, C-1’ or C-2’). IR (CHCl₃): ν = 3490, 3422, 2928, 1550, 1491, 1192 cm^–1. MS (ESI) m/z (%) = 747 (99.6) [M + Na]⁺, 748 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₂H₄₅NaO₉P 747.2699; found 747.2697, [M + Na]⁺ calcd for C₄₂H₄₄²HNaO₉P 748.2762; found 748.2764.

Radical Reactions of 6

Method A

Following the general procedure, starting from substrate 6 (39 mg, 0.045 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (12 μL, 0.045 mmol) was required. All the starting material was consumed after 6 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave 25 (9.7 mg, 0.020 mmol, 46%) and 3-C-(3,4,6-tri-O-benzyl-2-O-diphenoxyphosphoryl-β-d-mannopyranosyl)1-propanol (30α) (4 mg, 0.006 mmol, 12%) as a colorless oil. Compound 30α: [α]_D = +1.6 (c = 0.77, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.36–7.11 (m, 25H, Ar), 4.90 (ddd, J = 3.2, 3.2 Hz, ³J_PH = 6.3 Hz, 1H, 2-H), 4.74 (d, J = 11.4 Hz, 1H, OBn), 4.65 (d, J = 11.4 Hz, 1H, OBn), 4.56 (d, J = 12.0 Hz, 1H, OBn), 4.52 (d, J = 12.0 Hz, 1H, OBn), 4.47 (d, J = 11.4 Hz, 1H, OBn), 4.38 (d, J = 11.1 Hz, 1H, OBn), 4.04 (ddd, J = 10.1, 3.5, 3.5 Hz, 1H, 1-H), 3.85 (ddd, J = 8.2, 2.5 Hz, ⁴J_PH = 2.5 Hz, 1H, 3-H), 3.76 (ddd, J = 8.5, 5.4, 3.5 Hz, 1H, 5-H), 3.69–3.56 (m, 5H, 3’-H₂, 4-H, 6-H₂), 1.78–1.47 ppm (m, 4H, 1’-H₂, 2’-H₂), 1H from OH is missing. Stereochemistry was assigned as 1α since the starting phthalimide 6 was obtained by the reaction with N-hydroxyphthalimide under Mitsunobu conditions. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.7 (C, Ar), 150.5 (C, Ar), 138.1 (C, Ar), 138.0 (C, Ar), 137.6 (C, Ar), 129.8 (2 × CH, Ar), 129.6 (2 × CH, Ar), 128.38 (2 × CH, Ar), 128.36 (2 × CH, Ar), 128.3 (2 × CH, Ar), 128.2 (2 × CH, Ar), 128.0 (2 × CH, Ar), 127.8 (4 × CH, Ar), 127.6 (CH, Ar), 125.4 (CH, Ar), 125.1 (CH, Ar), 120.4 (CH, Ar), 120.3 (CH, Ar), 120.23 (CH, Ar), 120.19 (CH, Ar), 77.7 (d, ²J_PC = 6.4 Hz, CH, C-2), 77.6 (2 × CH, C-3, C-4), 74.5 (CH₂, OBn), 74.4 (CH, C-1), 73.4 (CH₂, OBn), 73.1 (CH, C-5), 72.1 (CH₂, OBn), 69.1 (CH₂, C-6), 61.8 (CH₂, C-3’), 29.4 (CH₂, C-1’ or C-2’), 29.1 ppm (CH₂, C-1’ or C-2’). IR (CHCl₃): ν = 3503, 2928, 1712, 1491, 1192 cm^–1. MS (ESI) m/z (%) = 747 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₂H₄₅NaO₉P 747.2699; found 747.2692.

Method D

Following the general procedure, starting from substrate 6 (30.2 mg, 0.035 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (9 μL, 0.035 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave (2-²H)25 (8.6 mg, 0.018 mmol, 52%) and 30α (4.7 mg, 0.005 mmol, 19%).

Method F

Following the general procedure, starting from substrate 6 (57.3 mg, 0.066 mmol), all the starting material was consumed after 1 h. Column chromatography (hexanes–EtOAc, 85:15 to 4:6) gave 25 (9 mg, 0.019 mmol, 29%) and 30α (24.2 mg, 0.033 mmol, 51%).

Method G

Following the general procedure, starting from substrate 6 (59 mg, 0.068 mmol), all the starting material was consumed after 3 h. Column chromatography (hexanes–EtOAc, 8:2 to 4:6) gave 25 (11.3 mg, 0.024 mmol, 35%) and 30α (22.1 mg, 0.031 mmol, 45%).

Radical Reactions of 7

Method A

Following the general procedure, starting from substrate 7 (74.6 mg, 0.11 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (30 μL, 0.11 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave 3-C-(2-O-acetyl-3,4,6-tri-O-benzyl-β-d-mannopyranosyl)1-propanol (29β) (56.8 mg, 0.11 mmol, 97%) as an amorphous solid: [α]_D = −27.6 (c = 0.87, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.35–7.15 (m, 15H, Ar), 5.474 (dd, J = 2.2, 0.0 Hz, 1H, 2-H), 4.85 (d, J = 10.7 Hz, 1H, OBn), 4.74 (d, J = 11.1 Hz, 1H, OBn), 4.61 (d, J = 12.0 Hz, 1H, OBn), 4.54 (d, J = 12.3 Hz, 1H, OBn), 4.48 (d, J = 11.0 Hz, 1H, OBn), 4.48 (d, J = 11.0 Hz, 1H, OBn), 3.74 (dd, J = 10.7, 1.9 Hz, 1H, 6-H_b), 3.70–3.63 (m, 5H, 3-H, 4-H, 5-H, 6-H_a, 3’-H_b), 3.51–3.46 (m, 2H, 1-H, 3’-H_a), 2.17 (s, 3H, OAc), 1.73–1.66 (m, 3H, 1’-H_b, 2’-H₂), 1.572 ppm (m, 1H, 1’-H_a), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.9 (C, OAc), 138.3 (C, Ar), 138.2 (C, Ar), 137.8 (C, Ar), 127.5–128.3 (15 × CH, Ar), 81.8 (CH), 79.2 (CH), 77.1 (CH, C-1), 75.1 (CH₂, OBn), 74.7 (CH), 73.4 (CH₂, OBn), 71.5 (CH₂, OBn), 69.49 (CH, C-2), 69.5 (CH₂, C-6), 62.4 (CH₂, C-3’), 29.3 (CH₂, C-2’), 28.08 (CH₂, C-1’), 20.9 ppm (CH₃, OAc). IR (CHCl₃): ν = 3430, 3015, 2936, 1735, 1091 cm^–1. MS (ESI) m/z (%) = 557 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₃₈NaO₇ 557.2515; found 557.2519. Anal. calcd for C₃₂H₃₈O₇: C, 71.89; H, 7.16. Found: C, 71.93; H, 7.08.

Method B

Following the general procedure, starting from substrate 7 (63.8 mg, 0.094 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (13 μL, 0.046 mmol) added by a syringe pump over 1 h was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave 29β (38.3 mg, 0.072 mmol, 76%).

Method C

Following the general procedure, starting from substrate 7 (63.9 mg, 0.094 mmol), after 3 h of reaction, a supplementary addition of TTMSS (29 μL, 0.094 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes–EtOAc, 7:3 to 1:1) gave 29β (28.8 mg, 0.054 mmol, 57%).

Method D

Following the general procedure, starting from substrate 7 (52.4 mg, 0.077 mmol), after 3 h of reaction, a supplementary addition of n-Bu₃SnD (21 μL, 0.077 mmol) was required. All the starting material was consumed after 6 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave 3-C-(2-O-acetyl-3,4,6-tri-O-benzyl-β-d-[1-²H]mannopyranosyl)1-propanol ([1-²H]29β) (30.8 mg, 0.057 mmol, 75%, ²H/¹H 5.8:1) as an amorphous solid: ¹H NMR (500 MHz, CDCl₃) δ_H 7.36–7.15 (m, 15H, Ar), 5.466 (d, J = 2.9 Hz, 1H, 2-H), 4.85 (d, J = 10.7 Hz, 1H, OBn), 4.74 (d, J = 11.1 Hz, 1H, OBn), 4.61 (d, J = 12.0 Hz, 1H, OBn), 4.54 (d, J = 12.3 Hz, 1H, OBn), 4.48 (d, J = 10.4 Hz, 1H, OBn), 4.48 (d, J = 10.4 Hz, 1H, OBn), 3.73 (dd, J = 10.8, 1.9 Hz, 1H, 6-H_b), 3.70–3.63 (m, 5H, 3-H, 4-H, 5-H, 6-H_a, 3’-H_b), 3.47 (ddd, J = 8.6, 6.0, 1.9 Hz, 1H, 3’-H_a), 2.18 (s, 3H, OAc), 1.71–1.66 (m, 3H, 1’-H_b, 2’-H₂), 1.566 ppm (m, 1H, 1’-H_a), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.9 (C, OAc), 138.3 (C, Ar), 138.2 (C, Ar), 137.8 (C, Ar), 127.6–128.4 (15 × CH, Ar), 81.8 (CH), 79.2 (CH), 75.1 (CH₂, OBn), 74.7 (CH), 73.4 (CH₂, OBn), 71.5 (CH₂, OBn), 69.50 (CH, C-2), 69.4 (CH₂, C-6), 62.5 (CH₂, C-3’), 29.4 (CH₂, C-2’), 28.06 (CH₂, C-1’), 21.0 ppm (CH₃, OAc), C-1 was undetectable. MS (ESI) m/z (%) = 558 (100) [M + Na]⁺, 557 (16) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₃₇²HNaO₇ 558.2578; found 558.2582, [M + Na]⁺ calcd for C₃₂H₃₈NaO₇ 557.2515; found 557.2511.

Method E

Following the general procedure, starting from substrate 7 (57.8 mg, 0.085 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (23 μL, 0.085 mmol) and BF₃•Et₂O (2 μL, 0.017 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave [2-²H]25 (20.2 mg, 0.043 mmol, 50%, ²H/¹H 1.6:1) and [1-²H]29β (8.6 mg, 0.016 mmol, 19%, ²H/¹H 3.5:1).

Radical Reactions of 8

Method A

Following the general procedure, starting from substrate 8 (60.4 mg, 0.07 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (19 μL, 0.07 mmol) was required. All the starting material was consumed after 6 h. Column chromatography (hexanes to hexanes–EtOAc, 8:2) gave 25 (12 mg, 0.025 mmol, 37%).

Method B

Following the general procedure, starting from substrate 8 (64.6 mg, 0.075 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (20 μL, 0.075 mmol) added by a syringe pump over 1 h was required. All the starting material was consumed after 11 h. Column chromatography (hexanes to hexanes–EtOAc, 8:2) gave 25 (13.7 mg, 0.029 mmol, 39%).

Method D

Following the general procedure, starting from substrate 8 (92.7 mg, 0.11 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (29 μL, 0.11 mmol) was required. All the starting material was consumed after 3 h. Column chromatography (hexanes to hexanes–EtOAc, 8:2) gave (2-²H)25 (26.3 mg, 0.055 mmol, 52%).

Method E

Following the general procedure, starting from substrate 8 (60 mg, 0.069 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (17 μL, 0.069 mmol) and BF₃•Et₂O (2 μL, 0.016 mmol) was required. All the starting material was consumed after 3 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave [2-²H]25 (20.2 mg, 0.043 mmol, 65%, ²H/¹H 2.4:1).

Method F

Following the general procedure, starting from substrate 8 (33.6 mg, 0.039 mmol), all the starting material was consumed after 2 h. Column chromatography (hexanes–EtOAc, 8:2 to 1:1) gave 25 (4.1 mg, 8.6·10^–3 mmol, 22%) and 3-C-(3,4,6-tri-O-benzyl-2-O-diphenoxyphosphoryl-β-d-mannopyranosyl)1-propanol (30β) (10.3 mg, 0.014 mmol, 37%) as a colorless oil. Compound 30β: [α]_D = −27.9 (c = 0.10, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.39–7.05 (m, 25H, Ar), 5.01 (dd, J = 9.0, 2.1, 1H, 2-H), 4.90 (d, J = 11.3 Hz, 1H, OBn), 4.63 (d, J = 11.1 Hz, 1H, OBn), 4.60 (d, J = 12.5 Hz, 1H, OBn), 4.53 (d, J = 12.2 Hz, 1H, OBn), 4.51 (d, J = 11.4 Hz, 1H, OBn), 4.29 (d, J = 10.8 Hz, 1H, OBn), 3.67 (dd, J = 10.8, 1.8 Hz, 1H), 3.63–3.56 (m, 3H), 3.54–3.49 (m, 2H), 3.44–3.40 (m, 2H), 1.68–1.54 ppm (m, 4H, 1’-H₂, 2’-H₂), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 150.9 (d, ²J_PC = 8.5 Hz, C, Ar), 150.7 (d, ²J_PC = 6.4 Hz, C, Ar), 138.2 (C, Ar), 138.1 (C, Ar), 137.6 (C, Ar), 129.7 (2 × CH, Ar), 129.4 (2 × CH, Ar), 128.4 (2 × CH, Ar), 128.33 (4 × CH, Ar), 128.26 (2 × CH, Ar), 128.0 (2 × CH, Ar), 127.8 (2 × CH, Ar), 127.70 (CH, Ar), 127.65 (CH, Ar), 127.6 (CH, Ar), 125.3 (CH, Ar), 124.8 (CH, Ar), 120.4 (CH, Ar), 120.3 (CH, Ar), 120.22 (CH, Ar), 120.16 (CH, Ar), 81.8 (CH, C-3), 79.2 (CH, C-5), 77.3 (CH, C-2), 77.2 (d, ³J_PC = 7.8 Hz, CH, C-1), 75.2 (CH₂, OBn), 74.1 (CH, C-4), 73.4 (CH₂, OBn), 71.7 (CH₂, OBn), 69.3 (CH₂, C-6), 62.4 (CH₂, C-3’), 29.3 (CH₂, C-1’ or C-2’), 28.1 ppm (CH₂, C-1’ or C-2’). IR (CHCl₃): ν = 3567, 2928, 2858, 1490, 1212 cm^–1. MS (ESI) m/z (%) = 747 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₂H₄₅NaO₉P 747.2699; found 747.2709.

Method G

Following the general procedure, starting from substrate 8 (37.1 mg, 0.043 mmol), all the starting material was consumed after 3 h. Column chromatography (hexanes–EtOAc, 8:2 to 1:1) gave 25 (6.5 mg, 0.014 mmol, 32%) and 30β (7.8 mg, 0.011 mmol, 25%).

Radical Reactions of 9

Method A

Following the general procedure, starting from substrate 9 (64.4 mg, 0.11 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (30 μL, 0.11 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave (4S)-1,4-anhydro-6,7-di-O-benzyl-2,3,5,9-tetradeoxy-β-l-lyxo-non-4-ulopyranose (31S) contaminated with the thermodynamic isomer (4R)-1,4-anhydro-6,7-di-O-benzyl-2,3,5,9-tetradeoxy-α-l-lyxo-non-4-ulopyranose (31R) (19.2 mg, 0.05 mmol, 46%, S/R, 85:15) as an amorphous solid and an inseparable mixture of 3-C-(2-O-acetyl-3,4-di-O-benzyl-6-deoxy-β-d-altropyranosyl)1-propanol (32) and 3-C-(2-O-acetyl-3,4-di-O-benzyl-α-l-fucopyranosyl)1-propanol (33) (7.4 mg, 0.017 mmol, 15%, 1:1.7) as a colorless oil. Compound 31S: ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.41–7.25 (m, 10H, Ar), 4.955 (d, J = 12.0 Hz, 1H, OBn), 4.73 (d, J = 11.7 Hz, 1H, OBn), 4.63 (d, J = 12.0 Hz, 1H, OBn), 4.60 (d, J = 12.0 Hz, 1H, OBn), 3.93 (ddd, J = 12.1, 4.5, 2.7 Hz, 1H, 3-H), 3.87 (ddd, J = 8.2, 8.2, 5.4 Hz, 1H, 3’-H_b), 3.82 (dddd, J = 6.5, 6.5, 6.5, 1.7 Hz, 1H, 5-H), 3.81 (ddd, J = 8.2, 8.2, 6.6 Hz, 1H, 3’-H_a), 3.58 (ddd, J = 2.7, 1.7 Hz, ⁴J_2a,4 = 1.3 Hz, 1H, 4-H), 2.32 (dd, J = 12.3, 12.1 Hz, 1H, 2-H_b), 2.13–2.00 (m, 2H, 1’-H_b, 2’-H_b), 1.92 (dd, J = 12.3, 4.5 Hz, ⁴J_2a,4 = 1.3 Hz, 1H, 2-H_a), 1.90 (m, 1H, 2’-H_a), 1.75 (m, 1H, 1’-H_a), 1.14 ppm (d, J = 6.5 Hz, 3H, 6-H₃), ¹H NMR (500 MHz, C₆D₆, simulated ring coupling constants using DAISY) δ_Η 7.44–7.42 (m, 2H, Ar), 7.38–7.35 (m, 2H, Ar), 7.22–7.13 (m, 6H, Ar), 5.05 (d, J = 11.5 Hz, 1H, C₄-OBn), 4.59 (d, J = 11.5 Hz, 1H, C₄-OBn), 4.44 (d, J = 12.1 Hz, 1H, C₃-OBn), 4.40 (d, J = 12.1 Hz, 1H, C₃-OBn), 4.02 (ddd, J = 12.0, 4.5, 2.7 Hz, 1H, 3-H), 3.87 (dddd, J = 6.5, 6.5, 6.5, 1.4 Hz, 1H, 5-H), 3.79–3.73 (m, 1H, 3’-H_b), 3.71–3.64 (m, 1H, 3’-H_a), 3.36 (ddd, J = 2.7, 1.4 Hz, ⁴J_2a,4 = 1.2 Hz, 1H, 4-H), 2.49 (dd, J = 12.1, 12.0 Hz, 1H, 2-H_b), 2.03–2.00 (m, 1H), 1.94 (ddd, J = 12.1, 4.5 Hz, ⁴J_2a,4 = 1.2 Hz, 1H, 2-H_a), 1.86–1.78 (m, 1H), 1.46–1.40 (m, 2H), 1.28 ppm (d, J = 6.5 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 139.0 (C, Ar), 138.8 (C, Ar), 128.5 (2 × CH, Ar), 128.4 (2 × CH, Ar), 128.1 (2 × CH, Ar), 127.2 (2 × CH, Ar), 127.2 (2 × CH, Ar), 106.8 (C, C-1), 77.3 (CH, C-3), 75.0 (CH, C-4), 74.16 (CH₂, OBn), 70.5 (CH₂, OBn), 67.6 (CH, C-5), 67.1 (CH₂, C-3’), 37.5 (CH₂, C-1’), 34.0 (CH₂, C-2), 23.6 (CH₂, C-2’), 17.4 ppm (CH₃, C-6). ¹³C{¹H} NMR (125.7 MHz, C₆D₆) δ_C 140.3 (C, Ar) some aromatic carbons were not observed, 140.0 (C, Ar), 107.4 (C, C-1), 78.0 (CH, C-3), 76.9 (CH, C-4), 75.3 (CH₂, OBn), 70.8 (CH₂, OBn), 68.5 (CH, C-5), 67.6 (CH₂, C-3’), 38.2 (CH₂, C-1’), 34.8 (CH₂, C-2), 24.4 (CH₂, C-2’), 18.1 ppm (CH₃, C-6). IR (CHCl₃): ν = 2930, 1226, 1206 cm^–1. MS (ESI) m/z (%) = 391 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₃H₂₈NaO₄ 391.1885; found 391.1891. Compounds 32 and 33: ¹H NMR (500 MHz, CDCl₃, selected signals of 32 from the mix spectrum) δ_H 4.95 (dd, J = 3.8, 1.6 Hz, 1H, 2-H), 4.72 (br s, 2H, OBn), 4.45 (d, J = 11.7 Hz, 1H, OBn), 4.34 (d, J = 11.7 Hz, 1H, OBn), 3.93 (dddd, J = 9.5, 6.3, 6.3, 6.3 Hz, 1H, 5-H), 3.88 (ddd, J = 9.2, 4.1, 1.3 Hz, 1H, 1-H), 3.248 (dd, J = 9.8, 3.2 Hz, 1H, 4-H), 1.286 ppm (d, J = 6.3 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, selected signals of 32 from the mix spectrum) δ_C 170.4 (C, OAc), 138.0 (C, Ar), 137.7 (C, Ar), 77.67 (CH, C-4), 73.4 (CH, C-1), 72.6 (CH₂, OBn), 71.7 (CH, C-3), 71.4 (CH, C-2), 71.3 (CH₂, OBn), 71.2 (CH, C-5), 62.6 (CH₂, C-3’), 27.6 (CH₂, C-1’ or C-2’), 26.1 (CH₂, C-1’ or C-2’), 8.19 ppm (CH₃, C-6). ¹H NMR (500 MHz, CDCl₃, selected signals of 33 from the mix spectrum) δ_H 5.08 (dd, J = 5.1, 2.6 Hz, 1H, 2-H), 4.76 (d, J = 12.0 Hz, 1H, OBn), 4.67 (d, J = 12.0 Hz, 1H, OBn), 4.63 (d, J = 12.0 Hz, 1H, OBn), 4.54 (d, J = 12.0 Hz, 1H, OBn), 4.14–4.06 (m, 2H, 1-H, 5-H), 3.75 (dd, J = 4.8, 3.2 Hz, 1H, 4-H), 1.41 ppm (d, J = 6.9 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, selected signals of 33 from the mix spectrum) δ_C 170.3 (C, OAc), 138.4 (C, Ar), 138.2 (C, Ar), 75.4 (CH, C-3), 74.2 (CH, C-4), 73.0 (CH₂, OBn), 72.0 (CH₂, OBn), 71.8 (CH, C-2), 70.0 (CH, C-5), 67.5 (CH, C-1), 62.6 (CH₂, C-3’), 29.7 (CH₂, C-1’ or C-2’), 29.4 (CH₂, C-1’ or C-2’), 14.2 ppm (CH₃, C-6). IR (CHCl₃): ν = 3690, 3018, 1735, 1222 cm^–1. MS (ESI) m/z (%) = 451 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₅H₃₂NaO₆ 451.2097; found 451.2095.

Method D

Following the general procedure, starting from substrate 9 (59.2 mg, 0.10 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (28 μL, 0.10 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave (4S)-1,4-anhydro-6,7-di-O-benzyl-2,3,5,9-tetradeoxy-β-l-[7-O-PhCH-²H]lyxo-non-4-ulopyranose ([PhCH-²H]31) (19.5 mg, 0.053 mmol, 53%, ²H/¹H 1.5:1) and a mixture of 3-C-(2-O-acetyl-3,4-di-O-benzyl-6-deoxy-β-d-(5-²H)altropyranosyl)1-propanol (5-²H)32 and 33 (15.8 mg, 0.037 mmol, 36%, ²H/¹H 1:2.8) as colorless oils. Compound [PhCH-²H]31: ¹H NMR (500 MHz, CDCl₃) δ_H 7.40–7.25 (m, 10H, Ar), 4.95 (d, J = 12.0 Hz, 0.4H, OBn), 4.93 (br s, 0.5H, O-CHD-Ph), 4.72 (d, J = 12.0 Hz, 0.4H, OBn), 4.71 (br s, 0.1H, O-CHD-Ph), 4.62 (d, J = 12.0 Hz, 1H, OBn), 4.59 (d, J = 12.0 Hz, 1H, OBn), 3.931 (ddd, J = 12.3, 4.4, 2.5 Hz, 0.5H, 3-H), 3.929 (ddd, J = 12.3, 5.0, 2.8 Hz, 0.5H, 3-H), 3.87 (ddd, J = 8.2, 8.2, 5.7 Hz, 1H, 3’-H_b), 3.82 (ddd, J = 8.2, 8.2, 6.6 Hz, 1H, 3’-H_a), 3.81 (m, 1H, 5-H), 3.57 (br s, 1H, 4-H), 2.32 (dd, J = 12.3, 12.3 Hz, 1H, 2-H_b), 2.13–1.99 (m, 2H, 1’-H_b, 2’-H_b), 1.92 (ddd, J = 12.3, 4.7 Hz, ⁴J_2a,4 = 1.0 Hz, 1H, 2-H_a), 1.85 (m, 1H, 2’-H_a), 1.74 (ddd, J = 12.3, 10.4, 7.9 Hz, 1H, 1’-H_a), 1.135 (d, J = 6.3 Hz, 1.5H, 6-H₃), 1.133 (d, J = 6.6 Hz, 0.3H, 6-H₃), 1.130 ppm (d, J = 6.3 Hz, 1.2H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 139.0 (0.4C, Ar), 138.9 (0.6C, Ar), 138.8 (C, Ar), 128.49 (CH, Ar), 128.45 (CH, Ar), 128.4 (2 × CH, Ar), 128.1 (2 × CH, Ar), 127.4 (2 × CH, Ar), 127.2 (2 × CH, Ar), 106.8 (C, C-1), 77.7 (CH, C-3), 75.09 (0.4CH, C-4), 75.02 (0.1CH, C-4), 74.97 (0.5CH, C-4), 74.18 (0.4CH₂, OBn), 73.59 (t, J_CD = 22.1 Hz, 0.6CHD-Ph), 70.5 (CH₂, OBn), 67.7 (CH, C-5), 67.1 (CH₂, C-3’), 37.5 (CH₂, C-1’), 34.0 (CH₂, C-2), 23.6 (CH₂, C-2’), 17.4 ppm (CH₃, C-6). ¹H NMR (500 MHz, C₆D₆) δ_H 7.44–7.42 (m, 2H, Ar), 7.36–7.35 (m, 2H, Ar), 7.22–7.10 (m, 6H, Ar), 5.046 (d, J = 11.6 Hz, 0.4H, OBn), 5.019 (br s, 0.5H, O-CHD-Ph), 4.59 (d, J = 11.5 Hz, 0.4H, OBn), 4.567 (br s, 0.1H, O-CHD-Ph), 4.44 (d, J = 12.1 Hz, 1H, OBn), 4.40 (d, J = 11.9 Hz, 1H, OBn), 4.02 (ddd, J = 12.1, 4.8, 2.8 Hz, 1H, 3-H), 3.89–3.85 (m, 1H, 5-H), 3.78–3.74 (m, 1H, 3’-H_b), 3.79–3.66 (m, 1H, 3’-H_a), 3.36 (m, 1H, 4-H), 2.496 (dd, J = 12.1, 12.1 Hz, 0.5H, 2-H_b), 2.494 (dd, J = 12.1, 12.1 Hz, 0.5H, 2-H_b), 2.02 (m, 1H), 1.94 (ddd, J = 12.6, 4.3 Hz, ⁴J_2a,4 = 0.6 Hz, 1H, 2-H_a), 1.86–1.78 (m, 1H), 1.46–1.40 (m, 2H), 1.280 (d, J = 6.6 Hz, 1.5H, 6-H₃), 1.276 ppm (d, J = 6.6 Hz, 1.5H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, C₆D₆) δ_C the aromatic carbons were not observed, 107.1 ppm (C, C-1), 77.7 (CH, C-3), 76.93 (0.4CH, C-4), 76.88 (0.1CH, C-4), 76.85 (0.5CH, C-4), 75.26 (0.4CH₂, OBn), 74.85 (t, J_CD = 22.1 Hz, 0.6CHD-Ph), 70.8 (CH₂, OBn), 68.5 (CH, C-5), 67.6 (CH₂, C-3’), 38.2 (CH₂, C-1’), 34.8 (CH₂, C-2), 24.4 (CH₂, C-2’), 18.2 ppm (CH₃, C-6). MS (ESI) m/z (%) = 392 (100) [M + Na]⁺, 391 (48) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₃H₂₇²HNaO₄ 392.1948; found 392.1936, [M + Na]⁺ calcd for C₂₃H₂₈NaO₄ 391.1885; found 391.1891. Mixture of (5-²H)32/33: ¹H NMR (400 MHz, CDCl₃, only the deuterated product (5-²H)32 is described) δ_H 7.40–7.22 (m, 10H, Ar), 4.95 (dd, J = 3.5, 1.2 Hz, 1H, 2-H), 4.72 (br s, 2H, OBn), 4.45 (d, J = 11.7 Hz, 1H, OBn), 4.34 (d, J = 11.7 Hz, 1H, OBn), 3.88 (ddd, J = 9.1, 5.3, 1.3 Hz, 1H, 1-H), 3.80 (m, 1H, 3-H), 3.69–3.58 (m, 2H, 3’-H₂), 3.248 (d, J = 3.1 Hz, 1H, 4-H), 2.06 (s, 3H, OAc), 1.67–1.45 (m, 4H, 1’-H₂, 2’-H₂), 1.280 ppm (s, 3H, 6-H₃), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃, only the deuterated product (5-²H)32 is described) δ_C 170.3 (C, OAc), 138.0 (C, Ar), 137.7 (C, Ar), 127.5–128.3 (10 × CH, Ar), 77.48 (CH, C-4), 73.3 (CH, C-1), 72.7 (CH₂, OBn), 71.8 (CH, C-3), 71.4 (CH, C-2), 71.4 (CH₂, OBn), 62.6 (CH₂, C-3’), 27.6 (CH₂, C-1’ or C-2’), 26.1 (CH₂, C-1’ or C-2’), 21.0 (CH₃, OAc), 18.07 ppm (CH₃, C-6). MS (ESI) m/z (%) = 452 (100) [M + Na]⁺, 451 (75) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₅H₃₁²HNaO₆ 452.2159; found 452.2159, [M + Na]⁺ calcd for C₂₅H₃₂NaO₆ 451.2097; found 451.2098.

Method F

Following the general procedure, starting from substrate 9 (17.9 mg, 0.031 mmol), all the starting material was consumed after 3 h. Column chromatography (hexanes–EtOAc, 6:4 to 4:6) gave 33 (8.7 mg, 0.020 mmol, 65%).

Method G

Following the general procedure, starting from substrate 9 (18.2 mg, 0.032 mmol), all the starting material was consumed after 3 h. Column chromatography (hexanes–EtOAc, 6:4 to 4:6) gave 33 (13.1 mg, 0.031 mmol, 67%).

Radical Reactions of 10

Method A

Following the general procedure, starting from substrate 10 (95.8 mg, 0.13 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (15 μL, 0.07 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 4:6) gave 31 (24.7 mg, 0.07 mmol, 52%, S/R, 83:17), 2,6:5,9-di-anhydro-3,4-di-O-benzyl-1,7,8-trideoxy-d-glycero-d-galacto-nonitol (36) (4.6 mg, 0.013 mmol, 10%), 3-C-(3,4-di-O-benzyl-6-deoxy-2-O-diphenoxyphosphoryl-β-d-altropyranosyl)1-propanol (34) (5.1 mg, 0.008 mmol, 6%), and 3-C-(3,4-di-O-benzyl-2-O-diphenoxyphosphoryl-α-l-fucopyranosyl)1-propanol (35) (9.7 mg, 0.016 mmol, 12%), all as colorless oils. Compound 36: [α]_D = +2.2 (c = 0.27, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.42–7.27 (m, 10H, Ar), 4.98 (d, J = 11.7 Hz, 1H, OBn), 4.88 (d, J = 12.3 Hz, 1H, OBn), 4.71 (d, J = 11.7 Hz, 1H, OBn), 4.70 (d, J = 12.3 Hz, 1H, OBn), 3.98 (m, 1H, 3’-H_b), 3.629 (dd, J = 9.8, 9.1 Hz, 1H, 2-H), 3.62 (dd, J = 3.0, 1.3 Hz, 1H, 4-H), 3.52 (dd, J = 9.8, 3.0 Hz, 1H, 3-H), 3.51 (dddd, J = 6.4, 6.4, 6.4, 1.3 Hz, 1H, 5-H), 3.46 (m, 1H, 3’-H_a), 3.06 (ddd, J = 11.1, 9.1, 4.3 Hz, 1H, 1-H), 2.038 (m, 1H, 1’-H_b), 1.75–1.70 (m, 2H, 2’-H₂), 1.611 (m, 1H, 1’-H_a), 1.16 ppm (d, J = 6.4 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 139.0 (C, Ar), 138.7 (C, Ar), 128.6 (2 × CH, Ar), 128.4 (2 × CH, Ar), 128.2 (2 × CH, Ar), 127.6 (CH, Ar), 127.52 (2 × CH, Ar), 127.47 (CH, Ar), 81.9 (CH, C-3), 79.60 (CH, C-2 or C-4), 77.88 (CH, C-2 or C-4), 76.4 (CH, C-1), 74.9 (CH, C-5), 74.9 (CH₂, OBn), 73.0 (CH₂, OBn), 67.9 (CH₂, C-3’), 29.12 (CH₂, C-1’), 25.6 (CH₂, C-2’), 17.3 ppm (CH₃, C-6). IR (CHCl₃): ν = 3017, 1454, 1220 cm^–1. MS (ESI) m/z (%) = 391 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₃H₂₈NaO₄ 391.1885; found 391.1878. Compound 34: [α]_D = +10.0 (c = 0.50, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.37–7.20 (m, 20H, Ar), 4.68 (d, J = 12.0 Hz, 1H, OBn), 4.62 (d, J = 12.0 Hz, 1H, OBn), 4.59 (m, 1H, 2-H), 4.21 (d, J = 11.7 Hz, 1H, OBn), 4.11 (d, J = 11.7 Hz, 1H, OBn), 4.03 (dd, J = 3.2, 3.2 Hz, 1H, 3-H), 3.90–3.81 (m, 2H, 1-H, 5-H), 3.57–3.54 (m, 2H, 3’-H₂), 3.240 (dd, J = 9.8, 2.9 Hz, 1H, 4-H), 1.63–1.50 (m, 4H, 1’-H₂, 2’-H₂), 1.262 ppm (d, J = 6.3 Hz, 3H, 6-H₃), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.5 (2 × C, Ar), 137.8 (2 × C, Ar), 129.9 (2 × CH, Ar), 129.8 (2 × CH, Ar), 128.4 (2 × CH, Ar), 128.3 (2 × CH, Ar), 128.1 (2 × CH, Ar), 127.9 (CH, Ar), 127.7 (3 × CH, Ar), 125.6 (2 × CH, Ar), 120.2 (CH, Ar), 120.1 (CH, Ar), 120.09 (CH, Ar), 120.06 (CH, Ar), 77.99 (CH, C-4), 77.3 (CH, C-2), 73.5 (d, ³J_PC = 6.4 Hz, CH, C-1), 73.0 (CH₂, OBn), 72.2 (CH, C-3), 71.5 (CH₂, OBn), 71.1 (CH, C-5), 62.6 (CH₂, C-3’), 29.3 (CH₂, C-1’), 27.5 (CH₂, C-2’), 18.23 ppm (CH₃, C-6). IR (CHCl₃): ν = 3426, 3022, 1490, 1220 cm^–1. MS (ESI) m/z (%) = 641 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₅H₃₉NaO₈P 641.2280; found 641.2288. Compound 35: [α]_D = −24.8 (c = 0.72, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.33–7.16 (m, 20H, Ar), 4.83 (ddd, J = 6.0, 2.8 Hz, ³J_PH = 8.5 Hz, 1H, 2-H), 4.70 (d, J = 11.7 Hz, 1H, OBn), 4.63 (d, J = 11.7 Hz, 1H, OBn), 4.54 (d, J = 12.0 Hz, 1H, OBn), 4.41 (d, J = 11.7 Hz, 1H, OBn), 4.09–4.04 (m, 2H, 1-H, 5-H), 3.92 (dd, J = 5.7, 3.2 Hz, 1H, 3-H), 3.721 (dd, J = 3.8, 3.8 Hz, 1H, 4-H), 3.55 (br s, 2H, 3’-H₂), 1.84 (br s, 1H, OH), 1.63–1.52 (m, 4H, 1’-H₂, 2’-H₂), 1.361 ppm (d, J = 6.9 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.5 (d, ²J_PC = 7.4 Hz, C, Ar), 150.5 (d, ²J_PC = 7.4 Hz, C, Ar), 138.2 (C, Ar), 138.0 (C, Ar), 129.81 (2 × CH, Ar), 129.76 (2 × CH, Ar), 128.4 (2 × CH, Ar), 128.3 (2 × CH, Ar), 127.7 (3 × CH, Ar), 127.62 (CH, Ar), 127.56 (2 × CH, Ar), 125.4 (2 × CH, Ar), 120.2 (CH, Ar), 120.12 (CH, Ar), 120.06 (CH, Ar), 120.0 (CH, Ar), 77.5 (CH, C-2), 75.9 (CH, C-3), 74.65 (CH, C-4), 73.2 (CH₂, OBn), 72.4 (CH₂, OBn), 69.6 (CH, C-5), 68.5 (d, ³J_PC = 4.2 Hz, CH, C-1), 62.4 (CH₂, C-3’), 29.7 (CH₂, C-1’), 29.2 (CH₂, C-2’), 14.44 ppm (CH₃, C-6). IR (CHCl₃): ν = 3454, 3015, 1490, 1205 cm^–1. MS (ESI) m/z (%) = 641 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₅H₃₉NaO₈P 641.2280; found 641.2278.

Method D

Following the general procedure, starting from substrate 10 (85.2 mg, 0.11 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (15 μL, 0.07 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 4:6) gave [PhCH-²H]31 (20.1 mg, 0.05 mmol, 49%, ²H/¹H 1.7:1), 2,6:5,9-di-anhydro-3,4-di-O-benzyl-1,7,8-trideoxy-d-[6-²H]glycero-d-galacto-nonitol [(1-²H)36] (4.5 mg, 0.012 mmol, 11%, ²H/¹H 8:1), and 3-C-(3,4-di-O-benzyl-6-deoxy-2-O-diphenoxyphosphoryl-β-d-(5-²H)altropyranosyl)1-propanol [(5-²H)34] (4.3 mg, 0.007 mmol, 6%) as colorless oils and 35 (6 mg, 0.01 mmol, 9%). Compound (1-²H)36: ¹H NMR (500 MHz, only the deuterated product is described) δ_H 7.42–7.26 (m, 10H, Ar), 4.98 (d, J = 11.7 Hz, 1H, OBn), 4.88 (d, J = 12.3 Hz, 1H, OBn), 4.71 (d, J = 11.7 Hz, 1H, OBn), 4.70 (d, J = 12.3 Hz, 1H, OBn), 3.98 (m, 1H, 3’-H_b), 3.637 (d, J = 9.8 Hz, 1H, 2-H), 3.62 (dd, J = 2.8, 1.0 Hz, 1H, 4-H), 3.52 (dd, J = 9.8, 2.8 Hz, 1H, 3-H), 3.51 (dddd, J = 6.3, 6.3, 6.3, 1.3 Hz, 1H, 5-H), 3.46 (m, 1H, 3’-H_a), 2.029 (m, 1H, 1’-H_b), 1.74–1.70 (m, 2H, 2’-H₂), 1.606 (m, 1H, 1’-H_a), 1.16 ppm (d, J = 6.7 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only the deuterated product is described) δ_C 138.9 (C, Ar), 138.6 (C, Ar), 128.5 (2 × CH, Ar), 128.3 (2 × CH, Ar), 128.1 (2 × CH, Ar), 127.54 (CH, Ar), 127.49 (2 × CH, Ar), 127.4 (CH, Ar), 81.9 (CH, C-3), 79.49 (CH, C-2), 77.84 (CH, C-4), 74.8 (CH, C-5), 74.8 (CH₂, OBn), 73.0 (CH₂, OBn), 67.9 (CH₂, C-3’), 28.99 (CH₂, C-1’), 25.6 (CH₂, C-2’), 17.3 ppm (CH₃, C-6). MS (ESI) m/z (%) = 392 (100) [M + Na]⁺, 391 (12) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₃H₂₇²HNaO₄ 392.1948; found 392.1954. Compound (5-²H)34: ¹H NMR (500 MHz, CDCl₃) δ_H 7.37–7.20 (m, 20H, Ar), 4.68 (d, J = 12.0 Hz, 1H, OBn), 4.62 (d, J = 12.0 Hz, 1H, OBn), 4.57 (m, 1H, 2-H), 4.20 (d, J = 11.7 Hz, 1H, OBn), 4.11 (d, J = 11.7 Hz, 1H, OBn), 4.02 (dd, J = 3.5, 3.5 Hz, 1H, 3-H), 3.83 (m, 1H, 1-H), 3.57–3.54 (m, 2H, 3’-H₂), 3.235 (d, J = 2.9 Hz, 1H, 4-H), 2.00 (br s, 1H, OH), 1.64–1.50 (m, 4H, 1’-H₂, 2’-H₂), 1.248 ppm (s, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.5 (2 × C, Ar), 137.9 (2 × C, Ar), 129.9 (2 × CH, Ar), 129.8 (2 × CH, Ar), 128.4 (2 × CH, Ar), 128.3 (2 × CH, Ar), 128.1 (2 × CH, Ar), 127.9 (CH, Ar), 127.7 (2 × CH, Ar), 127.4 (CH, Ar), 125.5 (2 × CH, Ar), 120.15 (CH, Ar), 120.10 (CH, Ar), 120.08 (CH, Ar), 120.04 (CH, Ar), 77.91 (CH, C-4), 77.3 (CH, C-2), 73.5 (d, ³J_PC = 6.4 Hz, CH, C-1), 73.0 (CH₂, OBn), 72.2 (CH, C-3), 71.5 (CH₂, OBn), 62.6 (CH₂, C-3’), 29.3 (CH₂, C-1’), 27.5 (CH₂, C-2’), 18.10 ppm (CH₃, C-6). MS (ESI) m/z (%) = 642 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₅H₃₈²HNaO₈P 642.2280; found 642.2291.

Radical Reactions of 11

Method A

Following the general procedure, starting from substrate 11 (68.2 mg, 0.10 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (29 μL, 0.10 mmol) was required. All the starting material was consumed after 3 h. Column chromatography (hexanes to hexanes–EtOAc, 9:1) gave (4S)-1,4-anhydro-6,7-O-benzylidene-2,3,5-trideoxy-d-erythro-oct-4-ulopyranose (37) (15.8 mg, 0.06 mmol, 60%) as a colorless oil: [α]_D = −109.3 (c = 0.28, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.48–7.46 (m, 2H, Ar), 7.40–7.35 (m, 3H, Ar), 6.20 (s, 1H, PhCH), 4.700 (ddd, J = 8.7, 6.3, 5.5 Hz, 1H, 3-H), 4.10 (ddd, J = 5.5, 2.4, 1.0 Hz, 1H, 4-H), 4.03 (dd, J = 13.3, 1.0 Hz, 1H, 5-H_b), 4.02 (dd, J = 13.3, 2.4 Hz, 1H, 5-H_a), 3.95 (ddd, J = 8.2, 8.2, 5.7 Hz, 1H, 3’-H_b), 3.88 (ddd, J = 8.2, 8.2, 6.3 Hz, 1H, 3’-H_a), 2.11 (dd, J = 13.5, 8.7 Hz, 1H, 2-H_b), 2.05 (dd, J = 13.5, 6.3 Hz, 1H, 2-H_a), 2.18–2.04 (m, 2H, 1’-H_b, 2’-H_b), 1.93 (m, 1H, 2’-H_a), 1.80 ppm (ddd, J = 12.3, 10.1, 7.9 Hz, 1H, 1’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 139.3 (C, Ar), 128.9 (CH, Ar), 128.4 (2 × CH, Ar), 126.1 (2 × CH, Ar), 105.75 (C, C-1), 102.6 (CH, PhCH), 71.83 (CH, C-4), 71.72 (CH, C-3), 67.4 (CH₂, C-3’), 60.6 (CH₂, C-5), 37.9 (CH₂, C-1’), 34.0 (CH₂, C-2), 23.6 ppm (CH₂, C-2’). IR (CHCl₃): ν = 3024, 1458, 1210 cm^–1. MS (ESI) m/z (%) = 285 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₅H₁₈NaO₄ 285.1103; found 285.1103. Anal. calcd for C₁₅H₁₈O₄: C, 68.68; H, 6.92. Found: C, 68.68; H, 7.00.

Method D

Following the general procedure, starting from substrate 11 (72.6 mg, 0.11 mmol), after 2 h, all the starting material was consumed. Column chromatography (hexanes to hexanes–EtOAc, 9:1) gave (4S)-1,4-anhydro-6,7-O-benzylidene-2,3,5-trideoxy-d-[5-²H]erythro-oct-4-ulopyranose ([2-²H]37) (15.7 mg, 0.06 mmol, 54%, ²H/¹H 1:1) as a colorless oil: ¹H NMR (500 MHz, CDCl₃, only the deuterated compound is described) δ_H 7.48–7.46 (m, 2H, Ar), 7.40–7.34 (m, 3H, Ar), 6.20 (s, 1H, PhCH), 4.701 (dd, J = 8.6, 5.4 Hz, 1H, 3-H), 4.11 (ddd, J = 5.4, 2.3, 1.3 Hz, 1H, 4-H), 4.03 (dd, J = 13.6, 1.0 Hz, 1H, 5-H_b), 4.00 (dd, J = 13.3, 2.2 Hz, 1H, 5-H_a), 3.94 (ddd, J = 8.2, 8.2, 5.7 Hz, 1H, 3’-H_b), 3.88 (ddd, J = 8.2, 8.2, 6.3 Hz, 1H, 3’-H_a), 2.18–2.04 (m, 3H, 2-H, 1’-H_b, 2’-H_b), 1.92 (m, 1H, 2’-H_a), 1.79 ppm (ddd, J = 12.3, 10.1, 7.9 Hz, 1H, 1’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only the deuterated compound is described) δ_C 139.3 (C, Ar), 128.9 (CH, Ar), 128.4 (2 × CH, Ar), 126.1 (2 × CH, Ar), 105.72 (C, C-1), 102.5 (CH, PhCH), 71.80 (CH, C-3 or C-4), 71.67 (CH, C-3 or C-4), 67.4 (CH₂, C-3’), 60.6 (CH₂, C-5), 37.9 (CH₂, C-1’), 33.69 (t, J_CD = 20.1 Hz, CHD, C-2), 23.6 ppm (CH₂, C-2’). MS (ESI) m/z (%) = 286 (100) [M + Na]⁺, 285 (83) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₅H₁₇²HNaO₄ 286.1166; found 286.1154, [M + Na]⁺ calcd for C₁₅H₁₈NaO₄ 285.1103; found 285.1107.

Method E

Following the general procedure, starting from substrate 11 (60 mg, 0.091 mmol), after 2 h, all the starting material was consumed. Column chromatography (hexanes to hexanes–EtOAc, 9:1) gave [2-²H]37 (14.4 mg, 0.055 mmol, 60%, ²H/¹H 1:1).

Radical Reactions of 12

Method A

Following the general procedure, starting from substrate 12 (65.2 mg, 0.11 mmol), all the starting material was consumed after 2 h. Column chromatography (DCM to DCM–MeOH, 97:3) gave (4S)-1,4-anhydro-2,3,5-trideoxy-d-erythro-oct-4-ulopyranose (38) (10.4 mg, 0.06 mmol, 54%) as a colorless oil: [α]_D = −57.3 (c = 0.62, CHCl₃). ¹H NMR (400 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 4.055 (ddd, J = 11.7, 5.3, 3.5 Hz, 1H, 3-H), 3.90 (dd, J = 12.5, 1.6 Hz, 1H, 5-H_b), 3.96–3.83 (m, 2H, 3’-H₂), 3.80 (br s, 1H, 4-H), 3.72 (dd, J = 12.5, 2.3 Hz, 1H, 5-H_a), 2.31 (br s, 1H, OH), 2.17 (br s, 1H, OH), 2.09–2.01 (m, 2H, 1’-H_b, 2’-H_b), 1.99 (dd, J = 12.8, 11.7 Hz, 1H, 2-H_b), 1.88 (m, 1H, 2’-H_a), 1.86 (dd, J = 12.8, 5.3 Hz, 1H, 2-H_a), 1.72 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 106.63 (C, C-1), 67.9 (CH, C-4), 67.5 (CH₂, C-3’), 66.59 (CH, C-3), 63.7 (CH₂, C-5), 37.5 (CH₂, C-1’), 36.83 (CH₂, C-2), 23.3 ppm (CH₂, C-2’). IR (CHCl₃): ν = 3685, 3571, 3020, 1056 cm^–1. MS (ESI) m/z (%) = 197 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₈H₁₄NaO₄ 197.0790; found 197.0789. Anal. calcd for C₈H₁₄O₄: C, 55.16; H, 8.10. Found: C, 54.97; H, 7.92.

Method D

Following the general procedure, starting from substrate 12 (64.2 mg, 0.11 mmol), after 2 h, all the starting material was consumed. Column chromatography (DCM to DCM–MeOH, 97:3) gave (4S)-1,4-anhydro-2,3,5-trideoxy-d-[5-²H]erythro-oct-4-ulopyranose ([2-²H]38) (12.2 mg, 0.07 mmol, 63%, ²H/¹H 2.3:1) as a colorless oil: ¹H NMR (500 MHz, CDCl₃, only the deuterated compound is described) δ_H 4.049 (m, 1H, 3-H), 3.95–3.85 (m, 2H, 3’-H₂), 3.90 (dd, J = 12.6, 1.3 Hz, 1H, 5-H_b), 3.80 (br s, 1H, 4-H), 3.72 (dd, J = 12.6, 2.2 Hz, 1H, 5-H_a), 2.22 (br s, 1H, OH), 2.09–2.00 (m, 2H, 1’-H_b, 2’-H_b), 1.92–1.85 (m, 2H, 2-H, 2’-H_a), 1.72 ppm (m, 1H, 1’-H_a), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only the deuterated compound is described) δ_C 106.57 (C, C-1), 67.9 (CH₂, C-4), 67.5 (CH₂, C-3’), 66.52 (CH, C-3), 63.7 (CH, C-5), 37.4 (CH₂, C-1’), 23.3 ppm (CH₂, C-2’), C-2 was undetectable. MS (ESI) m/z (%) = 198 (100) [M + Na]⁺, 197 (44) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₈H₁₃²HNaO₄ 198.0853; found 198.0856, [M + Na]⁺ calcd for C₈H₁₄NaO₄ 197.0790; found 197.0796.

Synthesis of 9-Deoxy-1,6-dioxaspiro[4.4]nonane structures (Table 4)

Radical Reactions of 13

Method A

Following the general procedure, starting from substrate 13 (102 mg, 0.12 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (32 μL, 0.12 mmol) was required. All the starting material was consumed after 3 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 8:2) gave 3-C-(2-O-acetyl-3,5-di-O-tert-butyldiphenylsilyl-α-d-ribofuranosyl)1-propanol (40) (51.2 mg, 0.072 mmol, 56%) as a colorless oil: [α]_D = +46.0 (c = 0.61, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.65–7.26 (m, 20H, Ar), 5.12 (dd, J = 4.4, 4.4 Hz, 1H, 2-H), 4.61 (dd, J = 6.7, 4.5 Hz, 1H, 3-H), 4.03 (m, 1H, 4-H), 3.97 (m, 1H, 1-H), 3.66–3.60 (m, 3H, 5-H_b, 3’-H₂), 3.32 (dd, J = 11.4, 3.5 Hz, 1H, 5-H_a), 2.13 (s, 3H, OAc), 1.69–1.53 (m, 4H, 1’-H₂, 2’-H₂), 1.02 (s, 9H, ^tBu), 0.91 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.4 (C, OAc). 135.78 (2 × CH, Ar), 135.72 (2 × CH, Ar), 135.60 (2 × CH, Ar), 135.55 (2 × CH, Ar), 133.3 (C, Ar), 133.24 (C, Ar), 133.22 (C, Ar), 132.7 (C, Ar), 129.98 (CH, Ar), 129.96 (CH, Ar), 129.5 (2 × CH, Ar), 127.76 (2 × CH, Ar), 127.72 (2 × CH, Ar), 127.56 (2 × CH, Ar), 127.54 (2 × CH, Ar), 82.8 (CH, C-4), 79.5 (CH, C-1), 75.0 (CH, C-2), 72.8 (CH, C-3), 63.6 (CH₂, C-5), 62.6 (CH₂, C-3’), 29.6 (CH₂, C-1’ or C-2’), 26.8 (3 × CH₃, ^tBu), 26.7 (3 × CH₃, ^tBu), 26.5 (CH₂, C-1’ or C-2’), 21.0 (CH₃, OAc), 19.2 (C, ^tBu), 19.1 ppm (C, ^tBu). IR (CHCl₃): ν = 3451, 2932, 1735, 1216, 1113 cm^–1. MS (ESI) m/z (%) = 733 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₂H₅₄NaO₆Si₂ 733.3357; found 733.3360. Anal. calcd for C₄₂H₅₄O₆Si₂: C, 70.95; H, 7.66. Found: C, 71.05; H, 7.82.

Method D

Following the general procedure, starting from substrate 13 (98.4 mg, 0.12 mmol), after 2 h of reaction and again after 4 h, a supplementary addition of n-Bu₃SnD (31 μL, 0.12 mmol) was required. All the starting material was consumed after 5 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 8:2) gave 3-C-(2-O-acetyl-3,5-di-O-tert-butyldiphenylsilyl-α-d-[1-²H]ribofuranosyl)1-propanol ([1-²H]40) (46.1 mg, 0.065 mmol, 54%, ²H/¹H 2:1) as a colorless oil: ¹H NMR (500 MHz, CDCl₃, only the deuterated compound is described) δ_H 7.65–7.26 (m, 20H, Ar), 5.117 (d, J = 4.7 Hz, 1H, 2-H), 4.61 (dd, J = 6.9, 4.7 Hz, 1H, 3-H), 4.03 (m, 1H, 4-H), 3.66–3.60 (m, 3H, 5-H_b, 3’-H₂), 3.31 (dd, J = 11.4, 3.5 Hz, 1H, 5-H_a), 2.13 (s, 3H, OAc), 1.69–1.53 (m, 4H, 1’-H₂, 2’-H₂), 1.02 (s, 9H, ^tBu), 0.91 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 170.4 (C, OAc), 135.79 (2 × CH, Ar), 135.73 (2 × CH, Ar), 135.61 (2 × CH, Ar), 135.56 (2 × CH, Ar), 133.4 (C, Ar), 133.28 (C, Ar), 133.25 (C, Ar), 132.7 (C, Ar), 129.98 (CH, Ar), 129.95 (CH, Ar), 129.5 (2 × CH, Ar), 127.76 (2 × CH, Ar), 127.72 (2 × CH, Ar), 127.56 (2 × CH, Ar), 127.54 (2 × CH, Ar), 82.8 (CH, C-4), 74.96 (CH, C-2), 72.8 (CH, C-3), 63.7 (CH₂, C-5), 62.6 (CH₂, C-3’), 29.6 (CH₂, C-1’ or C-2’), 26.8 (3 × CH₃, ^tBu), 26.7 (3 × CH₃, ^tBu), 26.5 (CH₂, C-1’ or C-2’), 21.0 (CH₃, OAc), 19.2 (C, ^tBu), 19.1 ppm (C, ^tBu). MS (ESI) m/z (%) = 734 (100) [M + Na]⁺, 733 (34) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₂H₅₃²HNaO₆Si₂ 734.3419; found 734.3417, [M + Na]⁺ calcd for C₄₂H₅₄NaO₆Si₂ 733.3357; found 733.3351.

Method E

Following the general procedure, starting from substrate 13 (128.6 mg, 0.15 mmol), after 2 h, a supplementary addition of n-Bu₃SnD (41 μL, 0.15 mmol) and BF₃•Et₂O (4 μL, 0.03 mmol) was required. All the starting material was consumed after 5 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 75:25) gave (4RS)-1,4-anhydro-5-O-acetyl-6,8-bis-O-tert-butyldiphenylsilyl-2,3-dideoxy-d-[5-²H]ribo-oct-4-ulofuranose ([2-²H]39) (39.1 mg, 0.06 mmol, 40%, ²H/¹H 1.3:1, 1R/1S 1:1) as a colorless oil and (1-²H)40 (13.9 mg, 0.02 mmol, 13%). Compound [2-²H]39: ¹H NMR (500 MHz, CDCl₃, only nondeuterated products of both isomers are described) δ_H 7.72–7.25 (m, 40H, Ar), 4.44 (m, 2H, 3-H), 4.12–4.08 (m, 2H, 4-H), 4.00 (ddd, J = 8.5, 8.5, 5.4 Hz, 1H, 3’-H_b), 3.90 (ddd, J = 7.6, 7.6, 7.6 Hz, 1H, 3’-H_a), 3.83 (ddd, J = 8.2, 8.2, 4.5 Hz, 1H, 3’-H_b), 3.70 (ddd, J = 7.6, 7.6, 7.6 Hz, 1H, 3’-H_a), 3.62 (dd, J = 11.4, 2.6 Hz, 1H, 5-H_b), 3.50 (dd, J = 10.8, 5.4 Hz, 1H, 5-H_b), 3.45 (dd, J = 11.0, 5.7 Hz, 1H, 5-H_a), 3.40 (dd, J = 11.0, 3.5 Hz, 1H, 5-H_a), 2.22 (dd, J = 9.5, 9.5 Hz, 1H, 1’-H_b), 2.12 (m, 1H, 2’-H_b), 2.10–1.96 (m, 6H, 1’-H_b, 2 × 2’-H₂, 2’-H_a, 2 × 2-H_b), 1.88–1.81 (m, 3H, 1’-H_a, 2 × 2-H_a), 1.73 (ddd, J = 12.0, 8.9, 8.9 Hz, 1H, 1’-H_a), 1.06 (s, 18H, ^tBu), 0.96 (s, 9H, ^tBu), 0.93 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only nondeuterated products of both isomers are described) δ_C 134.07 (C, Ar), 133.87 (C, Ar), 133.81 (C, Ar), 133.63 (2 × C, Ar), 133.61 (C, Ar), 133.59 (C, Ar), 133.5 (C, Ar), 127.5–135.9 (40 × CH, Ar), 114.8 (C, C-1), 114.2 (C, C-1), 86.9 (CH, C-4), 85.9 (CH, C-4), 74.1 (CH, C-3), 72.9 (CH, C-3), 67.4 (CH₂, C-3’), 67.1 (CH₂, C-3’), 65.0 (CH₂, C-5), 63.4 (CH₂, C-5), 44.3 (CH₂, C-2’), 43.5 (CH₂, C-2’), 36.8 (CH₂, C-1’), 36.1 (CH₂, C-1’), 27.0 (3 × CH₃, ^tBu), 26.9 (3 × CH₃, ^tBu), 26.8 (3 × CH₃, ^tBu), 26.7 (3 × CH₃, ^tBu), 24.22 (CH₂, C-2), 24.20 (CH₂, C-2), 19.19 (C, ^tBu), 19.16 (2 × C, ^tBu), 19.1 ppm (C, ^tBu). IR (CHCl₃): ν = 2932, 1428, 1222, 1113 cm^–1. MS (ESI) m/z (%) = 674 (100) [M + Na]⁺, 673 (33) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₄₉²HNaO₄Si₂ 674.3208; found 674.3206, [M + Na]⁺ calcd for C₄₀H₅₀NaO₄Si₂ 673.3145; found 673.3163.

Method F

Following the general procedure, starting from substrate 13 (40.8 mg, 0.048 mmol), all the starting material was consumed after 75 h. Chromatotron chromatography (hexanes–EtOAc, 7:3) gave (4RS)-1,4-anhydro-5-O-acetyl-6,8-bis-O-tert-butyldiphenylsilyl-2,3-dideoxy-d-ribo-oct-4-ulofuranose (39) (0.6 mg, 9.6·10^–4 mmol, 2%, 1R/1S 1:1) and 40 (22.8 mg, 0.032 mmol, 67%) as colorless oils. Compound 39: ¹H NMR (500 MHz, CDCl₃, descrived above for the [2-²H]39). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, descrived above for the [2-²H]39). MS (ESI) m/z (%) = 673 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₅₀NaO₄Si₂: 673.3145 [M + Na]⁺; found 673.3146. C₄₀H₅₀NaO₄Si₂ (650.99): calcd. C 73.80, H 7.74; found: C 73.70, H 7.74.

Radical Reactions of 14

Method A

Following the general procedure, starting from substrate 14 (56.9 mg, 0.06 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (16 μL, 0.06 mmol) was required. All the starting material was consumed after 4 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 7:3) gave 39 (18 mg, 0.028 mmol, 46%, 1R/1S 1.2:1).

Method D

Following the general procedure, starting from substrate 14 (54.5 mg, 0.06 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (16 μL, 0.06 mmol) was required. All the starting material was consumed after 5 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 7:3) gave [2-²H]39 (13 mg, 0.02 mmol, 35%, ²H/¹H 1:1.4).

Method E

Following the general procedure, starting from substrate 14 (49.8 mg, 0.05 mmol), after 4 h, the reaction was discarded since although the remaining starting material was present, several more polar products were detected in the TLC.

Method F

Following the general procedure, starting from substrate 14 (57.4 mg, 0.06 mmol), all the starting material was consumed after 0.75 h. Chromatotron chromatography (hexanes–EtOAc, 97:3 to 7:3) gave 39 (4.8 mg, 0.007 mmol, 12%, 1R/1S 1.2:1) and 3-C-(3,5-di-O-tert-butyldiphenylsilyl-2-O-trifluoromethanesulfonyl-α-d-ribofuranosyl)1-propanol (41) (20.3 mg, 0.025 mmol, 42%) as a colorless oil. Compound 41: [α]_D = +18.8 (c = 1.3, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.45–7.22 (m, 20H, Ar), 5.26 (dd, J = 4.1, 4.1 Hz, 1H, 2-H), 4.67 (dd, J = 4.8, 4.8 Hz, 1H, 3-H), 4.17 (ddd, J = 10.1, 3.2, 3.2 Hz, 1H, 1-H), 3.95 (ddd, J = 5.4, 2.9, 2.9 Hz, 1H, 4-H), 3.65 (m, 2H, 3’-H₂), 3.34 (dd, J = 11.7, 2.2 Hz, 1H, 5-H_b), 2.75 (dd, J = 11.7, 3.2 Hz, 1H, 5-H_a), 1.86 (m, 1H, 1’-H_b), 1.77–1.65 (m, 3H, 1’-H_a, 2’-H₂), 1.06 (s, 9H, ^tBu), 0.87 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 135.9 (2 × CH, Ar), 135.8 (2 × CH, Ar), 135.5 (4 × CH, Ar), 133.1 (C, Ar), 132.96 (C, Ar), 132.95 (C, Ar), 131.7 (C, Ar), 130.15 (CH, Ar), 130.10 (CH, Ar), 129.6 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.8 (2 × CH, Ar), 127.6 (4 × CH, Ar), 89.1 (CH, C-2), 82.8 (CH, C-4), 78.4 (CH, C-1), 73.3 (CH, C-3), 63.7 (CH₂, C-5), 62.4 (CH₂, C-3’), 29.4 (CH₂, C-1’), 26.7 (3 × CH₃, ^tBu), 26.6 (3 × CH₃, ^tBu), 26.5 (CH₂, C-2’), 19.2 (C, ^tBu), 19.0 ppm (C, ^tBu), 1C from CF₃ group is missing. IR (CHCl₃): ν = 3694, 3429, 3020, 2933, 2254, 1778, 1740, 1224, 1113 cm^–1. MS (ESI) m/z (%) = 823 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₁H₅₁F₃NaO₇SSi₂ 823.2744; found 823.2750. Anal. calcd for C₄₁H₅₁F₃O₇SSi₂: C, 61.47; H, 6.42; S, 4.00. Found: C, 61.20; H, 6.44; S, 3.62.

Radical Reactions of 15

Method A

Following the general procedure, starting from substrate 15 (93.8 mg, 0.12 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (31 μL, 0.12 mmol) was required. All the starting material was consumed after 3 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 97:3) gave (4R)-1,4-anhydro-2,3,5-trideoxy-6,8-bis-O-(1,1,3,3-tetraisopropyldisiloxanyl)-d-erythro-oct-4-ulofuranose (42) (13 mg, 0.031 mmol, 27%) and (4S)-1,4-anhydro-2,3,5-trideoxy-6,8-bis-O-(1,1,3,3-tetraisopropyldisiloxanyl)-d-erythro-oct-4-ulofuranose (43) (16.8 mg, 0.040 mmol, 35%), both as colorless oils. Compound 42: [α]_D = −56.6 (c = 0.53, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 4.64 (ddd, J = 8.9, 7.3, 5.4 Hz, 1H, 3-H), 3.95 (dd, J = 10.1, 2.5 Hz, 1H, 5-H_b), 3.89 (ddd, J = 8.2, 8.2, 5.4 Hz, 1H, 3’-H_b), 3.84–3.77 (m, 3H, 4-H, 5-H_a, 3’-H_a), 2.35 (dd, J = 12.3, 7.3 Hz, 1H, 2-H_b), 2.18 (dd, J = 12.7, 8.9 Hz, 1H, 2-H_a), 2.06 (ddd, J = 11.7, 11.7, 3.2 Hz, 1H, 1’-H_b), 2.02 (m, 1H, 2’-H_b), 1.93–1.82 (m, 2H, 1’-H_a, 2’-H_a), 1.10–0.99 ppm (m, 28H, ⁱPr). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 113.1 (C, C-1), 84.4 (CH, C-4), 74.7 (CH, C-3), 67.3 (CH₂, C-3’), 66.1 (CH₂, C-5), 44.0 (CH₂, C-2), 34.9 (CH₂, C-1’), 23.9 (CH₂, C-2’), 17.6 (CH₃, ⁱPr), 17.4 (3 × CH₃, ⁱPr), 17.3 (CH₃, ⁱPr), 17.1 (CH₃, ⁱPr), 17.02 (CH₃, ⁱPr), 16.99 (CH₃, ⁱPr), 13.4 (2 × CH, ⁱPr), 12.8 (CH, ⁱPr), 12.6 ppm (CH, ⁱPr). IR (CHCl₃): ν = 2947, 2868, 1464, 1136, 1035 cm^–1. MS (ESI) m/z (%) = 439 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₀H₄₀NaO₅Si₂ 439.2312; found 439.2308. Anal. calcd for C₂₀H₄₀O₅Si₂: C, 57.65; H, 9.68. Found: C, 57.39; H, 9.46. Compound 43: [α]_D = +20.8 (c = 0.89, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 4.33 (ddd, J = 8.2, 8.2, 6.9 Hz, 1H, 3-H), 3.99 (dd, J = 11.4, 2.2 Hz, 1H, 5-H_b), 3.94–3.89 (m, 2H, 3’-H₂), 3.86–3.80 (m, 2H, 4-H, 5-H_a), 2.38 (dd, J = 13.3, 8.2 Hz, 1H, 2-H_b), 2.23 (dd, J = 13.2, 7.3 Hz, 1H, 2-H_a), 2.08–2.01 (m, 2H, 1’-H_b, 2’-H_b), 1.91–1.82 (m, 2H, 1’-H_a, 2’-H_a), 1.10–0.99 ppm (m, 28H, ⁱPr). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 112.7 (C, C-1), 82.9 (CH, C-4), 71.5 (CH, C-3), 67.3 (CH₂, C-3’), 62.3 (CH₂, C-5), 43.3 (CH₂, C-2), 36.5 (CH₂, C-1’), 24.2 (CH₂, C-2’), 17.5 (CH₃, ⁱPr), 17.36 (2 × CH₃, ⁱPr), 17.35 (CH₃, ⁱPr), 17.27 (CH₃, ⁱPr), 17.2 (CH₃, ⁱPr), 17.0 (CH₃, ⁱPr), 16.9 (CH₃, ⁱPr), 13.5 (CH, ⁱPr), 13.2 (CH, ⁱPr), 12.8 (CH, ⁱPr), 12.6 ppm (CH, ⁱPr). IR (CHCl₃): ν = 2947, 2868, 1465, 1210, 1133, 1043 cm^–1. MS (ESI) m/z (%) = 439 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₀H₄₀NaO₅Si₂ 439.2312; found 439.2312. Anal. calcd for C₂₀H₄₀O₅Si₂: C, 57.65; H, 9.68. Found: C, 57.39; H, 9.46.

Method D

Following the general procedure, starting from substrate 15 (93.7 mg, 0.12 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (31 μL, 0.12 mmol) was required. All the starting material was consumed after 6 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 97:3) gave (4R)-1,4-anhydro-2,3,5-trideoxy-6,8-bis-O-(1,1,3,3-tetraisopropyldisiloxanyl)-β-d-[5-²H]erythro-oct-4-ulofuranose ([2-²H]42) (11.7 mg, 0.02 mmol, 24%, ²H/¹H 1.2:1) and (4S)-1,4-anhydro-2,3,5-trideoxy-6,8-bis-O-(1,1,3,3-tetraisopropyldisiloxanyl)-β-d-[5-²H]erythro-oct-4-ulofuranose ([2-²H]43) (10 mg, 0.024 mmol, 21%, ²H/¹H 1.5:1), which was obtained as a 1:1.2 mixture with [2-²H]42. Compound [2-²H]42: ¹H NMR (500 MHz, CDCl₃, only deuterated 2RS isomers are described) δ_H 4.64 (m, 1H, 3-H), 3.96–3.87 (m, 2H, 5-H_b, 3’-H_b), 3.84–3.77 (m, 3H, 4-H, 5-H_a, 3’-H_a), 2.336 (d, J = 7.3 Hz, 1H, 2-H, 2R isomer), 2.166 (d, J = 9.2 Hz, 1H, 2-H, 2S isomer), 2.06 (ddd, J = 11.4, 11.4, 2.9 Hz, 1H, 1’-H_b), 2.01 (m, 1H, 2’-H_b), 1.93–1.83 (m, 2H, 1’-H_a, 2’-H_a), 1.10–0.99 ppm (m, 28H, ⁱPr). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only deuterated 2RS isomers are described) δ_C 113.1 (C, C-1), 84.4 (CH, C-4), 74.60 (CH, C-3), 67.3 (CH₂, C-3’), 66.1 (CH₂, C-5), 43.68 (t, J_CD = 22.2 Hz, CHD, C-2), 34.9 (CH₂, C-1’), 23.9 (CH₂, C-2’), 17.6 (CH₃, ⁱPr), 17.4 (3 × CH₃, ⁱPr), 17.3 (CH₃, ⁱPr), 17.1 (CH₃, ⁱPr), 17.02 (CH₃, ⁱPr), 16.99 (CH₃, ⁱPr), 13.4 (2 × CH, ⁱPr), 12.8 (CH, ⁱPr), 12.6 ppm (CH, ⁱPr). MS (ESI) m/z (%) = 440 (100) [M + Na]⁺, 439 (68) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₀H₃₉²HNaO₅Si₂ 440.2375; found 440.2372, [M + Na]⁺ calcd for C₂₀H₄₀NaO₅Si₂ 439.2312; found 439.2300. Compound [2-²H]43: ¹H NMR (500 MHz, CDCl₃, only deuterated 2RS isomers are described) δ_H 4.33 (ddd, J = 8.2, 8.2, 6.9 Hz, 1H, 3-H), 3.99 (dd, J = 11.4, 2.2 Hz, 1H, 5-H_b), 3.94–3.89 (m, 2H, 3’-H₂), 3.86–3.80 (m, 2H, 4-H, 5-H_a), 2.365 (d, J = 8.5 Hz, 1H, 2-H), 2.228 (d, J = 6.9 Hz, 1H, 2-H), 2.08–2.01 (m, 2H, 1’-H_b, 2’-H_b), 1.91–1.82 (m, 2H, 1’-H_a, 2’-H_a), 1.10–0.99 ppm (m, 28H, ⁱPr). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 112.7 (C, C-1), 82.9 (CH, C-4), 71.5 (CH, C-3), 67.3 (CH₂, C-3’), 62.3 (CH₂, C-5), 42.95 (t, J_CD = 21.2 Hz, CHD, C-2), 36.5 (CH₂, C-1’), 24.2 (CH₂, C-2’), 17.5 (CH₃, ⁱPr), 17.4 (2 × CH₃, ⁱPr), 17.3 (2 × CH₃, ⁱPr), 17.2 (CH₃, ⁱPr), 17.0 (CH₃, ⁱPr), 16.9 (CH₃, ⁱPr), 13.5 (CH, ⁱPr), 13.2 (CH, ⁱPr), 12.8 (CH, ⁱPr), 12.6 ppm (CH, ⁱPr). IR (CHCl₃): ν = 2947, 2868, 1465, 1210, 1133, 1043 cm^–1. MS (ESI) m/z (%) = 440 (100) [M + Na]⁺, 439 (55) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₀H₃₉²HNaO₅Si₂ 440.2375; found 440.2374, [M + Na]⁺ calcd for C₂₀H₄₀NaO₅Si₂ 439.2312; found 439.2306.

Method F

Following the general procedure, starting from substrate 15 (53.8 mg, 0.066 mmol), all the starting material was consumed after 0.5 h. Chromatotron chromatography (hexanes–EtOAc, 95:5 to 1:1) gave 42 and 43 (7.3 mg, 0.018 mmol, 26%, 1R/1S 1:2.5), and 3-C-(2-O-diphenoxyphosphoryl-3,5-bis-O-(1,1,3,3-tetraisopropyldisiloxanyl)-α-d-ribofuranosyl)1-propanol (44) (9.5 mg, 0.014 mmol, 22%) as a colorless oil. Compound 44: [α]_D = +12.9 (c = 0.71, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.33–7.15 (m, 10H, Ar), 5.13 (ddd, J = 3.8, 3.8 Hz, ³J_PH = 7.9 Hz, 1H, 2-H), 4.47 (m, 1H, 3-H), 4.12 (m, 1H, 1-H), 4.00 (dd, J = 12.6, 2.8 Hz, 1H, 5-H_b), 3.95–3.91 (m, 2H, 4-H, 5-H_a), 3.51–3.49 (m, 2H, 3’-H₂), 1.66–1.51 (m, 4H, 1’-H₂, 2’-H₂), 1.09–0.81 ppm (m, 28H, ⁱPr), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.9 (d, ²J_PC = 7.4 Hz, C, Ar), 150.6 (d, ²J_PC = 7.4 Hz, C, Ar), 129.7 (2 × CH, Ar), 129.6 (2 × CH, Ar), 125.3 (CH, Ar), 125.1 (CH, Ar), 120.19 (CH, Ar), 120.14 (CH, Ar), 120.0 (CH, Ar), 119.9 (CH, Ar), 81.6 (d, ²J_PC = 6.4 Hz, CH, C-2), 79.8 (CH, C-4), 79.5 (d, ³J_PC = 6.3 Hz, CH, C-1), 71.6 (CH, C-3), 62.5 (CH₂, C-3’), 60.9 (CH₂, C-5), 29.2 (CH₂, C-1’ or C-2’), 26.7 (CH₂, C-1’ or C-2’), 17.4 (CH₃, ⁱPr), 17.28 (CH₃, ⁱPr), 17.27 (CH₃, ⁱPr), 17.25 (CH₃, ⁱPr), 17.0 (2 × CH₃, ⁱPr), 16.8 (CH₃, ⁱPr), 16.7 (CH₃, ⁱPr), 13.5 (CH, ⁱPr), 13.1 (CH, ⁱPr), 12.6 (CH, ⁱPr), 12.4 ppm (CH, ⁱPr). IR (CHCl₃): ν = 3692, 3610, 3022, 2948, 1490.1210, 1039 cm^–1. MS (ESI) m/z (%) = 689 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₅₁NNaO₉PSi₂ 689.2707; found 689.2706. Anal. calcd for C₃₂H₅₁NO₉PSi₂: C, 57.63; H, 7.71. Found: C, 57.61; H, 8.07.

Synthesis of 4-Deoxy-6,8-dioxabicyclo[3.2.1]heptane Structures (Tables 5 and 6)

Radical Reactions of 16

Method A

Following the general procedure, starting from substrate 16 (49 mg, 0.076 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (20 μL, 0.076 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave (2S)-2,7-anhydro-1-O-tert-butyldiphenylsilyl-3-deoxy-4,5-di-O-methyl-β-d-xylo-hept-2-ulopyranose (45) (3.1 mg, 0.007 mmol, 9%), an inseparable mixture of 48 (7.6 mg, 0.015 mmol, 20%) and unstable C-(6-O-tert-butyldiphenylsilyl-4-deoxy-2,3-di-O-methyl-β-l-threo-hex-4-enopyranosyl)methanol (46) (1.5 mg, 0.03 mmol, 4%), and C-(4-O-acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-β-l-idopyranosyl)methanol (47) (12.1 mg, 0.024 mmol, 32%), all as colorless oils. Compound 45: [α]_D = +14.5 (c = 0.38, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.70–7.68 (m, 4H, Ar), 7.45–7.37 (m, 6H, Ar), 4.56 (ddd, J = 5.0, 4.3, 0.0 Hz, 1H, 1-H), 4.03 (dd, J = 7.6, 0.0 Hz, 1H, 1’-H_b), 3.75 (d, J = 11.0 Hz, 1H, 6-H_b), 3.73 (d, J = 10.7 Hz, 1H, 6-H_a), 3.68 (dd, J = 7.5, 5.0 Hz, ⁴J_2,1’_a = 1.1 Hz, 1H, 1’-H_a), 3.571 (ddd, J = 10.1, 8.2, 6.6 Hz, 1H, 3-H), 3.50 (s, 3H, OMe), 3.42 (s, 3H, OMe), 3.40 (ddd, J = 8.2, 4.4 Hz,⁴J_2,1’_a = 1.1 Hz, 1H, 2-H), 2.36 (dd, J = 13.0, 6.6 Hz, 1H, 4-H_b), 1.70 (dd, J = 13.0, 10.1 Hz, 1H, 4-H_a), 1.08 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 135.68 (2 × CH, Ar), 135.67 (2 × CH, Ar), 133.2 (2 × C, Ar), 129.7 (2 × CH, Ar), 127.7 (4 × CH, Ar), 107.94 (C, C-5), 81.0 (CH, C-2), 77.78 (CH, C-3), 73.7 (CH, C-1), 66.8 (CH₂, C-6), 65.8 (CH₂, C-1’), 58.4 (CH₃, OMe), 57.2 (CH₃, OMe), 37.08 (CH₂, C-4), 26.8 (3 × CH₃, DPS), 19.3 ppm (C, DPS). IR (CHCl₃): ν = 2931, 1464, 1113 cm^–1. MS (ESI) m/z (%) = 465 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₅H₃₄NaO₅Si 465.2073; found 465.2071. Anal. calcd for C₂₅H₃₄O₅Si: C, 67.84; H, 7.74. Found: C, 67.63; H, 7.68. Compound 46: could not be purified perfectly due to its instability. ¹H NMR (500 MHz, CDCl₃, simulated coupling constants of the allylic system using DAISY) δ_H 7.74–7.34 (m, 10H, Ar), 5.23 (dddd, J = 4.9 Hz, ⁴J = 1.5, 1.5, 1.0 Hz, 1H, 4-H), 4.16 (ddd, J = 13.9 Hz, ⁴J = 1.0 Hz, ⁵J = 1.6 Hz, 1H, 6-H_b), 4.12 (ddd, J = 13.9 Hz, ⁴J = 1.5 Hz, ⁵J = 0.7 Hz, 1H, 6-H_a), 3.98–3.92 (m, 2H, 1-H, 1’-H_b), 3.81 (m, 1H, 1’-H_a), 3.72 (dddd, J = 4.9, 2.3 Hz, ⁵J = 1.6, 0.7 Hz, 1H, 3-H), 3.454 (s, 3H, OMe), 3.450 (m, 1H, 2-H), 3.42 (s, 3H, OMe), 1.08 ppm (s, 9H, ^tBu), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 156.0 (C, C-5), 135.58 (2 × CH, Ar), 135.56 (2 × CH, Ar), 133.3 (2 × C, Ar), 129.7 (2 × CH, Ar), 127.7 (4 × CH, Ar), 92.8 (CH, C-4), 76.5 (CH, C-3), 74.1 (CH, C-1), 69.4 (CH, C-2), 62.7 (2 × CH₂, C-1, C-6), 58.0 (CH₃, OMe), 55.4 (CH₃, OMe), 26.8 (3 × CH₃, DPS), 19.3 ppm (C, DPS). IR (CHCl₃): ν = 3674, 3504, 2931, 1113 cm^–1. MS (ESI) m/z (%) = 465 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₅H₃₄NaO₅Si 465.2073; found 465.2061. Compound 47: [α]_D = +0.4 (c = 1.20, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.64–7.61 (m, 4H, Ar), 7.45–7.35 (m, 6H, Ar), 5.074 (ddd, J = 2.6, 1.9, ⁴J_2,4 = 1.2 Hz, 1H, 4-H), 4.01 (ddd, J = 9.1, 5.2, 1.6 Hz, 1H, 5-H), 3.94 (dd, J = 11.7, 8.0 Hz, 1H, 1’-H_b), 3.81 (dd, J = 9.8, 5.2 Hz, 1H, 6-H_b), 3.79 (ddd, J = 8.0, 4.0, 1.6 Hz, 1H, 1-H), 3.78 (dd, J = 11.7, 9.1 Hz, 1H, 6-H_a), 3.74 (dd, J = 2.7, 2.6 Hz, 1H, 3-H), 3.63 (dd, J = 11.7, 4.0 Hz, 1H, 1’-H_a), 3.55 (s, 3H, OMe), 3.36 (s, 3H, OMe), 3.20 (ddd, J = 2.7, 1.6, ⁴J_2,4 = 1.2 Hz, 1H, 2-H), 2.03 (s, 3H, OAc), 1.85 (br s, 1H, OH), 1.04 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 170.8 (C, OAc), 135.6 (2 × CH, Ar), 135.5 (2 × CH, Ar), 133.3 (C, Ar), 133.2 (C, Ar), 129.74 (CH, Ar), 129.72 (CH, Ar), 127.7 (4 × CH, Ar), 76.3 (CH, C-1 or C-2), 76.1 (CH, C-1 or C-2), 74.6 (CH, C-5), 71.7 (CH, C-3), 66.20 (CH, C-4), 62.6 (CH₂, C-1’), 61.62 (CH₂, C-6), 58.1 (CH₃, OMe), 58.0 (CH₃, OMe), 26.8 (3 × CH₃, DPS), 21.0 (CH₃, OAc), 19.1 ppm (C, DPS). IR (CHCl₃): ν = 3675, 3594, 2933, 1731, 1103 cm^–1. MS (ESI) m/z (%) = 525 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₇H₃₈NaO₇Si 525.2285; found 525.2276. Anal. calcd for C₂₇H₃₈O₇Si: C, 64.51; H, 7.62. Found: C, 64.81; H, 7.86.

Method C

Following the general procedure, starting from substrate 16 (54.5 mg, 0.084 mmol), after 2 h of reaction, a supplementary addition of TTMSS (26 μL, 0.084 mmol) was required. All the starting material was consumed after 7 h. Column chromatography (hexanes–EtOAc, 9:1 to 7:3) gave 45 (4.1 mg, 0.009 mmol, 11%) and 46 (10.8 mg, 0.024 mmol, 29%).

Method D

Following the general procedure, starting from substrate 16 (69.9 mg, 0.11 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (29 μL, 0.11 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave 2,7-anhydro-1-O-tert-butyldiphenylsilyl-3-deoxy-4,5-di-O-methyl-β-d-[3-²H]xylo-hept-2-ulopyranose ([4-²H]45) (5.3 mg, 0.011 mmol, 10%, ²H/¹H 1.8:1, 4R/4S 1:1.2), an inseparable mixture of reduced alcohol 48 (7.6 mg, 0.015 mmol, 14%) and olefin 46 (10.7 mg, 0.024 mmol, 22%), and C-(4-O-acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-β-l-(5-²H)idopyranosyl)methanol [(5-²H)47] (18.3 mg, 0.036 mmol, 33%), all as colorless oils. Compound [4-²H]45: ¹H NMR (500 MHz, CDCl₃, only deuterated 4RS isomers are described) δ_H 7.70–7.65 (m, 4H, DPS), 7.45–7.37 (m, 6H, DPS), 4.56 (ddd, J = 4.4, 4.4, 0.0 Hz, 1H, 1-H), 4.03 (dd, J = 7.3, 0.0 Hz, 1H, 1’-H_b), 3.75 (d, J = 11.0 Hz, 1H, 6-H_b), 3.73 (d, J = 11.0 Hz, 1H, 6-H_a), 3.70–3.66 (m, 1H, 1’-H_a), 3.60–3.54 (m, 1H, 3-H), 3.50 (s, 3H, OMe), 3.43 (s, 3H, OMe), 3.42 (dd, J = 8.8, 3.5 Hz, 1H, 2-H), 2.35 (d, J = 6.6 Hz, 1H, 4-H, 4R isomer), 1.69 (d, J = 10.1 Hz, 1H, 4-H, 4S isomer), 1.08 ppm (s, 18H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃, only deuterated 4RS isomers are described) δ_C 135.68 (2 × CH, DPS), 135.66 (2 × CH, DPS), 133.27 (C, DPS), 133.20 (C, DPS), 129.7 (2 × CH, DPS), 127.7 (4 × CH, DPS), 107.90 (C, C-5), 81.0 (CH, C-2), 77.73 (CH, C-3, 4R or 4S isomer), 77.70 (CH, C-3, 4R or 4S isomer), 73.7 (CH, C-1), 66.8 (CH₂, C-6), 65.8 (CH₂, C-1’), 58.4 (CH₃, OMe), 57.2 (CH₃, OMe), 36.75 (t, J_CD = 19.1 Hz, CHD, C-4), 26.8 (3 × CH₃, DPS), 19.3 ppm (C, DPS). MS (ESI) m/z (%) = 466 (100) [M + Na]⁺, 465 (46) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₅H₃₃²HNaO₅Si 466.2136; found 466.2141, [M + Na]⁺ calcd for C₂₅H₃₄NaO₅Si 465.2073; found 465.2060. Compound (5-²H)47: ¹H NMR (400 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.64–7.61 (m, 4H, Ar), 7.45–7.35 (m, 6H, Ar), 5.070 (dd, J = 2.7 Hz, ⁴J_2,4 = 1.2 Hz, 1H, 4-H), 3.93 (dd, J = 11.7, 8.1 Hz, 1H, 1’-H_b), 3.81 (d, J = 9.6 Hz, 1H, 6-H_a), 3.79 (d, J = 9.6 Hz, 1H, 6-H_b), 3.79 (ddd, J = 8.1, 4.0, 1.6 Hz, 1H, 1-H), 3.73 (dd, J = 2.7, 2.7 Hz, 1H, 3-H), 3.62 (dd, J = 11.7, 4.0 Hz, 1H, 1’-H_a), 3.55 (s, 3H, OMe), 3.36 (s, 3H, OMe), 3.19 (ddd, J = 2.7, 1.6 Hz, ⁴J_2,4 = 1.2 Hz, 1H, 2-H), 2.03 (s, 3H, OAc), 1.04 ppm (s, 9H, ^tBu), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 170.8 (C, OAc), 135.6 (2 × CH, Ar), 135.5 (2 × CH, Ar), 133.3 (C, Ar), 133.2 (C, Ar), 129.74 (CH, Ar), 129.71 (CH, Ar), 127.7 (4 × CH, Ar), 76.2 (CH, C-1 or C-2), 76.1 (CH, C-1 or C-2), 71.7 (CH, C-3), 66.14 (CH, C-4), 62.6 (CH₂, C-1’), 61.54 (CH₂, C-6), 58.1 (CH₃, OMe), 58.0 (CH₃, OMe), 26.8 (3 × CH₃, DPS), 21.0 (CH₃, OAc), 19.1 ppm (C, DPS). MS (ESI) m/z (%) = 526 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₇H₃₇²HNaO₇Si 526.2347; found 526.2346.

Method E

Following the general procedure, starting from substrate 16 (38.3 mg, 0.059 mmol), after 2 h, a supplementary addition of n-Bu₃SnD (16 μL, 0.059 mmol) and BF₃•Et₂O (2 μL, 0.012 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave [4-²H]45 (10.3 mg, 0.023 mmol, 39%, ²H/¹H 2.9:1, 4R/4S 1:1.2), an inseparable mixture of 48 (4.6 mg, 0.009 mmol, 15%) and unstable 46 (4.6 mg, 0.010 mmol, 18%), and (5-²H)47 (7.3 mg, 0.015 mmol, 25%).

Radical Reactions of 17

Method A

Following the general procedure, starting from substrate 17 (49 mg, 0.058 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (16 μL, 0.058 mmol) was required. All the starting material was consumed after 5 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 9:1) gave 45 (14 mg, 0.032 mmol, 55%).

Method D

Following the general procedure, starting from substrate 17 (59.6 mg, 0.071 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (19 μL, 0.071 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 9:1) gave [4-²H]45 (18.1 mg, 0.041 mmol, 58%, ²H/¹H 2.3:1, 4R/4S 1:1.2).

Radical Reactions of 18

Method A

Following the general procedure, starting from substrate 18 (38 mg, 0.05 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (13 μL, 0.05 mmol) was required. All the starting material was consumed after 6 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 9:1) gave 45 (11.7 mg, 0.027 mmol, 53%).

Method D

Following the general procedure, starting from substrate 18 (38.8 mg, 0.05 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnD (14 μL, 0.05 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 9:1) gave [4-²H]45 (13 mg, 0.029 mmol, 58%, ²H/¹H 1.7:1, 4R/4S 1:1.2).

Method F

Following the general procedure, starting from substrate 18 (12.4 mg, 0.016 mmol), all the starting material was consumed after 1.5 h. Chromatotron chromatography (hexanes–EtOAc, 8:2 to 4:6) gave 45 (1.4 mg, 0.003 mmol, 19%) and 49 (4.1 mg, 0.007 mmol, 41%).

Method G

Following the general procedure, starting from substrate 18 (14.1 mg, 0.019 mmol), all the starting material was consumed after 3 h. Chromatotron chromatography (hexanes–EtOAc, 8:2 to 4:6) gave 45 (3.2 mg, 0.007 mmol, 39%) and 49 (2.3 mg, 0.004 mmol, 20%).

Radical Reactions of 19

Method A

Following the general procedure, starting from substrate 19 (72.6 mg, 0.087 mmol), after 2 h, a supplementary addition of n-Bu₃SnH (24 μL, 0.087 mmol) was required. All the starting material was consumed after 3 h. Column chromatography (hexanes to hexanes–EtOAc, 2:8) gave 2,7-anhydro-3-deoxy-1-O-diphenoxyfosforyl-4,5-di-O-methyl-β-d-xylo-hept-2-ulopyranose (53) (11.5 mg, 0.026 mmol, 30%) and 1,5-anhydro-4,6-bis-O-diphenoxyphosphoryl-2,3-di-O-methyl-d-glucitol (54) (11 mg, 0.017 mmol, 19%) as colorless oils. Compound 53: [α]_D = +2.6 (c = 0.46, CHCl₃). ¹H NMR (400 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.36–7.17 (m, 10H, Ar), 4.54 (ddd, J = 5.1, 3.9, 0.0 Hz, 1H, 1-H), 4.29 (d, ³J_PH = 8.2 Hz, 2H, 6-H₂), 4.02 (dd, J = 7.7, 0.0 Hz, 1H, 1’-H_b), 3.65 (ddd, J = 7.5, 5.1 Hz, ⁴J_2,1’_a = 1.1 Hz, 1H, 1’-H_a), 3.528 (ddd, J = 10.0, 7.8, 6.5 Hz, 1H, 3-H), 3.47 (s, 3H, OMe), 3.36 (ddd, J = 7.8, 3.9 Hz, ⁴J_2,1’_a = 1.1 Hz, 1H, 2-H), 3.36 (s, 3H, OMe), 2.29 (dd, J = 12.9, 6.5 Hz, 1H, 4-H_b), 1.52 ppm (dd, J = 12.9, 10.0 Hz, 1H, 4-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.5 (d, ²J_PC = 6.3 Hz, 2 × C, Ar), 120.1–129.8 (10 × CH, Ar), 105.65 (d, ³J_PC = 7.4 Hz, C, C-5), 80.4 (CH, C-2), 77.31 (CH, C-3), 73.9 (CH, C-1), 69.3 (d, ²J_PC = 5.3 Hz, CH₂, C-6), 66.2 (CH₂, C-1’), 58.5 (CH₃, OMe), 57.1 (CH₃, OMe), 36.76 ppm (CH₂, C-4). IR (CHCl₃): ν = 2929, 1490, 1232 cm^–1. MS (ESI) m/z (%) = 459 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₁H₂₅NaO₈P 459.1185; found 459.1175. Compound 54: [α]_D = +27.0 (c = 0.70, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.33–7.10 (m, 20H, Ar), 4.42 (ddd, J = 11.6, 2.0 Hz, ³J_PH = 8.2 Hz, 1H, 6-H_b), 4.36 (ddd, J = 9.7, 9.1 Hz, ³J_PH = 9.4 Hz, 1H, 4-H), 4.13 (ddd, J = 11.6, 5.9 Hz, ³J_PH = 9.8 Hz, 1H, 6-H_a), 3.950 (dd, J = 11.3, 5.2 Hz, 1H, 1-H_b), 3.51 (ddd, J = 9.7, 5.9, 2.0 Hz, 1H, 5-H), 3.45 (s, 3H, OMe), 3.43 (s, 3H, OMe), 3.29 (dd, J = 9.1, 8.8 Hz, 1H, 3-H), 3.207 (ddd, J = 10.6, 8.8, 5.2 Hz, 1H, 2-H), 3.040 ppm (dd, J = 11.3, 10.6 Hz, 1H, 1-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.7 (d, ²J_PC = 7.4 Hz, C, Ar), 150.6 (d, ²J_PC = 7.4 Hz, C, Ar), 150.5 (d, ²J_PC = 7.4 Hz, C, Ar), 150.4 (d, ²J_PC = 7.4 Hz, C, Ar), 120.0–129.8 (20 × CH, Ar), 84.9 (CH, C-3), 79.82 (CH, C-2), 76.7 (CH, C-5), 75.8 (d, ²J_PC = 6.3 Hz, CH, C-4), 67.5 (d, ²J_PC = 6.4 Hz, CH₂, C-6), 67.19 (CH₂, C-1), 60.5 (CH₃, OMe), 58.7 ppm (CH₃, OMe). IR (CHCl₃): ν = 3020, 2929, 1490, 1218 cm^–1. MS (ESI) m/z (%) = 679 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₃₄NaO₁₁P₂ 679.1474; found 679.1474.

Radical Reactions of 20

Method A

Following the general procedure, starting from substrate 20 (89 mg, 0.14 mmol), after 2 h of reaction, a supplementary addition of n-Bu₃SnH (37 μL, 0.14 mmol) was required. All the starting material was consumed after 5 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 75:25) gave an inseparable mixture of C-(4-O-acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-β-l-altropyranosyl)methanol (50) and 51 (33 mg, 0.066 mmol, 47%, 2:1) as a colorless oil, and 46 (12.1 mg, 0.027 mmol, 20%). Compounds 50 and 51: ¹H NMR (500 MHz, CDCl₃, only 50 is described) δ_H 7.73–7.63 (m, 4H, Ar), 7.46–7.35 (m, 6H, Ar), 5.144 (dd, J = 10.1, 2.9 Hz, 1H, 4-H), 3.93–3.77 (m, 7H, 1-H, 3-H, 5-H, 6-H₂, 1’-H₂), 3.46 (s, 3H, OMe), 3.45 (s, 3H, OMe), 3.37 (dd, J = 3.8, 1.0 Hz, 1H, 2-H), 2.03 (s, 3H, OAc), 1.05 ppm (s, 9H, ^tBu), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃, only 50 is described) δ_C 169.9 (C, OAc), 135.8 (2 × CH, Ar), 135.6 (2 × CH, Ar), 133.9 (C, Ar), 133.6 (C, Ar), 129.5 (2 × CH, Ar), 127.6 (2 × CH, Ar), 127.5 (2 × CH, Ar), 77.5 (CH, C-2), 74.7 (CH, C-1 or C-5), 74.4 (CH, C-1 or C-5), 74.4 (CH, C-3), 68.55 (CH, C-4), 63.88 (CH₂, C-6), 62.8 (CH₂, C-1’), 59.2 (CH₃, OMe), 58.2 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 20.9 (CH₃, OAc), 19.3 ppm (C, DPS). IR (CHCl₃): ν = 3690, 3567, 2933, 1737, 1217 cm^–1. MS (ESI) m/z (%) = 525 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₇H₃₈NaO₇Si 525.2285; found 525.2267. Anal. calcd for C₂₇H₃₈O₇Si: C, 64.51; H, 7.62. Found: C, 64.58; H. 7.84.

Method D

Following the general procedure, starting from substrate 20 (38 mg, 0.06 mmol), after 2 h of reaction and again after 4 h, a supplementary addition of n-Bu₃SnD (16 μL, 0.06 mmol) was required. All the starting material was consumed after 9 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 8:2) gave an inseparable mixture of three compounds, (5-²H)50 and 51 (19.3 mg, 0.04 mmol, 66%, 2.3:1) and olefin 46 (3.3 mg, 0.007 mmol, 13%), as a colorless oil. Mixture of (5-²H)50/51/46: ¹H NMR (400 MHz, CDCl₃, only (5-²H)50 is described) δ_H 7.73–7.60 (m, 4H, Ar), 7.44–7.32 (m, 6H, Ar), 5.137 (d, J = 3.1 Hz, 1H, 4-H), 3.94–3.76 (m, 6H, 1-H, 3-H, 6-H₂, 1’-H₂), 3.45 (s, 6H, 2 × OMe), 3.37 (dd, J = 3.8, 1.0 Hz, 1H, 2-H), 2.03 (s, 3H, OAc), 1.05 ppm (s, 9H, ^tBu), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃, only (5-²H)50 is described) δ_C 169.9 (C, OAc), 135.8 (4 × CH, Ar), 133.4 (C, Ar), 133.3 (C, Ar), 129.5 (2 × CH, Ar), 127.5 (4 × CH, Ar), 77.6 (CH, C-2), 74.7 (CH, C-1), 74.5 (CH, C-3), 68.53 (CH, C-4), 63.84 (CH₂, C-6), 62.7 (CH₂, C-1’), 59.3 (CH₃, OMe), 58.2 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 20.9 (CH₃, OAc), 19.3 ppm (C, DPS). MS (ESI) m/z (%) = 526 (100) [M + Na]⁺, 525 (48) [M + Na]⁺, 465 (54) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₇H₃₇²HNaO₇Si 526.2358; found 526.2358, [M + Na]⁺ calcd for C₂₇H₃₈NaO₇Si 525.2285; found 525.2282, [M + Na]⁺ calcd for C₂₅H₃₄NaO₅Si 465.2073; found 465.2089.

Method F

Following the general procedure, starting from substrate 20 (57 mg, 0.088 mmol), all the starting material was consumed after 2 h. Chromatotron chromatography (hexanes–EtOAc, 8:2 to 7:3) gave 45 (4.67 mg, 0.011 mmol, 12%) and an inseparable mixture of 50 and 51 (22.1 mg, 0.044 mmol, 50%, 1.2:1).

Method G

Following the general procedure, starting from substrate 20 (43 mg, 0.066 mmol), all the starting material was consumed after 3 h. Chromatotron chromatography (hexanes–EtOAc, 8:2 to 7:3) gave 45 (6.1 mg, 0.014 mmol, 21%) and an inseparable mixture of 50 and 51 (14.6 mg, 0.029 mmol, 44%, 1.3:1).

Radical Reactions of 21

Method A

Following the general procedure, starting from substrate 21 (75.7 mg, 0.09 mmol), all the starting material was consumed after 2 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 7:3) gave olefin 46 (18.1 mg, 0.041 mmol, 45%) and alcohol 52 (13.8 mg, 0.020 mmol, 22%).

Method C

Following the general procedure, starting from substrate 21 (73 mg, 0.087 mmol), after 2 h of reaction, a supplementary addition of TTMSS (27 μL, 0.087 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes–EtOAc, 8:2) gave 45 (9.6 mg, 0.022 mmol, 25%) and 52 (14.5 mg, 0.021 mmol, 24%).

Method D

Following the general procedure, starting from substrate 21 (74.3 mg, 0.089 mmol), all the starting material was consumed after 2 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 1:1) gave C-(6-O-tert-butyldiphenylsilyl-4-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-d-[2-OMe-²H]galactopyranosyl)methanol ([OCH₂-²H]52) (14.2 mg, 0.020 mmol, 23%, ²H/¹H 1.3:1) and olefin 46 (17.3 mg, 0.039 mmol, 44%), both as colorless oils. Compound [OCH₂-²H]52: ¹H NMR (500 MHz, CDCl₃, only the deuterated product is described) δ_H 7.65–7.05 (m, 20H, Ar), 5.05 (ddd, J = 2.8, 2.2 Hz, ³J_PH = 8.8 Hz, 1H, 4-H), 4.09 (ddd, J = 7.3, 5.7, 5.7 Hz, 1H, 1-H), 3.80–3.70 (m, 5H, 5-H, 6-H₂, 1’-H₂), 3.57 (dd, J = 8.5, 5.7 Hz, 1H, 2-H), 3.38 (m, 1H, 3-H), 3.372 (t, J = 1.6 Hz, 2H, OCH₂D), 3.35 (s, 3H, OMe), 1.03 ppm (s, 9H, ^tBu), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only the deuterated product is described) δ_C 150.8 (d, ²J_PC = 7.4 Hz, C, Ar), 150.4 (d, ²J_PC = 7.4 Hz, C, Ar), 135.6 (2 × CH, Ar), 135.5 (2 × CH, Ar), 133.3 (C, Ar), 133.2 (C, Ar), 129.8 (CH, Ar), 129.72 (CH, Ar), 129.65 (2 × CH, Ar), 129.4 (2 × CH, Ar), 127.7 (4 × CH, Ar), 125.2 (CH, Ar), 125.1 (CH, Ar), 120.34 (CH, Ar), 120.30 (CH, Ar), 120.02 (CH, Ar), 119.98 (CH, Ar), 78.7 (CH, C-3), 77.0 (CH, C-2), 74.2 (d, ²J_PC = 6.3 Hz, CH, C-4), 72.9 (d, ³J_PC = 5.3 Hz, CH, C-5), 72.6 (CH, C-1), 62.2 (CH₂, C-6), 59.3 (CH₂, C-1’), 59.26 (CH₂D), 57.7 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 19.1 ppm (C, DPS). MS (ESI) m/z (%) = 716 (100) [M + Na]⁺, 715 (67) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₇H₄₄²HNaO₉PSi 716.2531; found 716.2554, M + Na]⁺ calcd for C₃₇H₄₅NaO₉PSi 715.2468; found 715.2471.

Method E

Following the general procedure, starting from substrate 21 (81.8 mg, 0.098 mmol), after 2 h, a supplementary addition of n-Bu₃SnD (26 μL, 0.098 mmol) and BF₃•Et₂O (3 μL, 0.024 mmol) was required. All the starting material was consumed after 3 h. Column chromatography on a silica gel without KF (hexanes to hexanes–EtOAc, 1:1) gave [4-²H]45 (17.8 mg, 0.040 mmol, 41%, ²H/¹H 2.8:1, 4R/4S 1:1.2) and [OCH₂-²H]52 (8.6 mg, 0.012 mmol, 13%, ²H/¹H 1.1:1).

Method F

Following the general procedure, starting from substrate 21 (36.9 mg, 0.044 mmol), all the starting material was consumed after 3 h. Chromatotron chromatography (hexanes–EtOAc, 8:2 to 4:6) gave 52 (15.8 mg, 0.023 mmol, 52%).

Method G

Following the general procedure, starting from substrate 21 (40.5 mg, 0.048 mmol), all the starting material was consumed after 3 h. Chromatotron chromatography (hexanes–EtOAc, 8:2 to 4:6) gave 52 (13.5 mg, 0.019 mmol, 40%).

Radical Reactions of 22

Method A

Following the general procedure, starting from substrate 22 (106.8 mg, 0.18 mmol), after 2 h, a supplementary addition of n-Bu₃SnH (49 μL, 0.18 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave 2,7-anhydro-1,3-dideoxy-4,5-di-O-methyl-β-l-ribo-hept-2-ulopyranose (61) (18.9 mg, 0.10 mmol, 56%) as a colorless oil. [α]_D = +0.02 (c = 0.34, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 4.75 (ddd, J = 5.8, 2.8, 0.9 Hz, 1H, 1-H), 3.82 (dd, J = 7.7, 5.8 Hz, 1H, 1’-H_b), 3.67 (dd, J = 7.7, 0.9 Hz, 1H, 1’-H_a), 3.626 (ddd, J = 11.1, 6.0, 4.1 Hz, 1H, 3-H), 3.46 (dd, J = 4.1, 2.8 Hz, 1H, 2-H), 3.56 (s, 3H, OMe), 3.38 (s, 3H, OMe), 2.121 (dd, J = 12.5, 6.0 Hz, 1H, 4-H_b), 1.816 (dd, J = 12.5, 11.1 Hz, 1H, 4-H_a), 1.51 ppm (s, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 106.96 (C, C-5), 75.4 (CH, C-2), 74.1 (CH, C-1), 73.78 (CH, C-3), 65.8 (CH₂, C-1’), 57.9 (CH₃, OMe), 56.2 (CH₃, OMe), 38.69 (CH₂, C-4), 23.8 ppm (CH₃, C-6). IR (CHCl₃): ν = 3015, 2934, 1389, 1198 cm^–1. MS (ESI) m/z (%) = 211 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₉H₁₆NaO₄ 211.0946; found 211.0948. Anal. calcd for C₉H₁₆O₄: C, 57.43; H, 8.57. Found: C, 57.63; H, 8.63.

Method C

Following the general procedure, starting from substrate 22 (58.8 mg, 0.10 mmol), after 2 h of reaction, a supplementary addition of TTMSS (31 μL, 0.10 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes–EtOAc, 9:1 to 6:4) gave 61 (9 mg, 0.048 mmol, 48%).

Method D

Following the general procedure, starting from substrate 22 (61.5 mg, 0.105 mmol), after 2 h, a supplementary addition of n-Bu₃SnD (29 μL, 0.105 mmol) was required. All the starting material was consumed after 5 h. Column chromatography (hexanes to hexanes–EtOAc, 1:1) gave 2,7-anhydro-1,3-dideoxy-4,5-di-O-methyl-β-l-[4-²H]ribo-hept-2-ulopyranose ([4-²H]61) (8.7 mg, 0.046 mmol, 44%, ²H/¹H 1.8:1, 4R/4S 1:1.3) as a colorless oil: ¹H NMR (500 MHz, CDCl₃, only deuterated isomers are described) δ_H 4.75 (ddd, J = 5.7, 2.8, 0.0 Hz, 1H, 1-H), 3.82 (dd, J = 7.6, 5.7 Hz, 1H, 1’-H_b), 3.67 (dd, J = 7.9, 0.0 Hz, 1H, 1’-H_a), 3.63–3.60 (m, 1H, 3-H), 3.55 (s, 3H, OMe), 3.47–3.44 (m, 1H, 2-H), 3.38 (s, 3H, OMe), 2.101 (d, J = 5.7 Hz, 1H, 4-H, 4S isomer), 1.793 (d, J = 11.1 Hz, 1H, 4-H, 4R isomer), 1.51 ppm (s, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only deuterated isomers are described) δ_C 106.92 (C, C-5), 75.4 (CH, C-2), 74.1 (CH, C-1), 73.69 (CH, C-3), 65.8 (CH₂, C-1’), 57.8 (CH₃, OMe), 56.2 (CH₃, OMe), 38.52 (t, J_CD = 20.1 Hz, CHD, C-4), 23.8 ppm (CH₃, C-6). MS (ESI) m/z (%) = 212 (100) [M + Na]⁺, 211 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₉H₁₅²HNaO₄ 212.1009; found 212.1005, [M + Na]⁺ calcd for C₉H₁₆NaO₄ 211.0946; found 211.0948.

Method E

Following the general procedure, starting from substrate 22 (77 mg, 0.13 mmol), after 2 h, a supplementary addition of n-Bu₃SnD (35 μL, 0.13 mmol) and BF₃·Et₂O (3.3 μL, 0.026 mmol) was required. All the starting material was consumed after 7 h. Column chromatography (hexanes to hexanes–EtOAc, 6:4) gave [4-²H]61 (16.2 mg, 0.086 mmol, 66%, ²H/¹H 1.3:1, 4R/4S 1:1.3).

Method F

Following the general procedure, starting from substrate 22 (28.9 mg, 0.05 mmol), all the starting material was consumed after 1.5 h. Chromatotron chromatography (hexanes–EtOAc, 4:6 to 3:7) gave 61 (5.2 mg, 0.028 mmol, 55%).

Method G

Following the general procedure, starting from substrate 22 (29.1 mg, 0.050 mmol), all the starting material was consumed after 3 h. Chromatotron chromatography (hexanes–EtOAc, 4:6 to 3:7) gave 61 (5.7 mg, 0.030 mmol, 61%).

Radical Reactions of 23

Method A

Following the general procedure, starting from substrate 23 (88 mg, 0.22 mmol), after 2 h, a supplementary addition of n-Bu₃SnH (60 μL, 0.22 mmol) was required. All the starting material was consumed after 6 h. Column chromatography (hexanes to hexanes–EtOAc, 4:6) gave C-(4,6-dideoxy-2,3-di-O-methyl-β-d-threo-hex-4-enopyranosyl)methanol (56) (8.3 mg, 0.044 mmol, 20%) and C-(4-O-acetyl-2,3-6-deoxy-di-O-methyl-β-d-altropyranosyl)methanol (57) (4.4 mg, 0.018 mmol, 8%) as colorless oils, and 58 (7.8 mg, 0.031 mmol, 14%). Compound 56: [α]_D = −119.1 (c = 0.45, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 4.78 (br ddd, J = 5.3 Hz, ⁴J = 2.0, 0.9 Hz, 1H, 4-H), 4.01 (dd, J = 11.4, 6.4 Hz, 1H, 1’-H_b), 3.94 (ddd, J = 6.4, 4.1, 1.5 Hz, 1H, 1-H), 3.86 (br dd, J = 11.4, 4.1 Hz, 1H, 1’-H_a), 3.60 (ddd, J = 5.3, 2.0 Hz, ⁵J = 1.0 Hz, 1H, 3-H), 3.45 (s, 3H, OMe), 3.40 (ddd, J = 2.0, 1.5 Hz, ⁴J = 2.0 Hz, 1H, 2-H), 3.39 (s, 3H, OMe), 2.25 (br s, 1H, OH), 1.86 ppm (dd, ⁵J = 1.0 Hz, ⁴J = 0.9 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 154.7 (C, C-5), 93.7 (CH, C-4), 75.7 (CH, C-2), 73.8 (CH, C-1), 69.7 (CH, C-3), 63.0 (CH₂, C-1’), 58.1 (CH₃, OMe), 55.4 (CH₃, OMe), 20.0 ppm (CH₃, C-6). IR (CHCl₃): ν = 3691, 3602, 3013, 2933, 1672, 1226 cm^–1. MS (ESI) m/z (%) = 211 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₉H₁₆NaO₄ 211.0946; found 211.0942. Anal. calcd for C₉H₁₆O₄: C, 57.43; H, 8.57. Found: C, 57.10; H, 8.27. Compound 57: [α]_D = +50.3 (c = 0.35, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 4.799 (dd, J = 10.1, 3.2 Hz, 1H, 4-H), 3.92–3.84 (m, 4H, 1-H, 2-H, 5-H, 1’-H_b), 3.67 (m, 1H, 1’-H_a), 3.464 (s, 3H, OMe), 3.462 (s, 3H, OMe), 3.40 (dd, J = 3.8, 1.0 Hz, 1H, 3-H), 2.12 (s, 3H, OAc), 1.201 ppm (d, J = 6.4 Hz, 3H, 6-H₃), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.2 (C, OAc), 77.7 (CH, C-3), 74.7 (CH, C-2), 74.2 (CH, C-1), 73.40 (CH, C-4), 69.68 (CH, C-5), 62.7 (CH₂, C-1’), 59.3 (CH₃, OMe), 58.4 (CH₃, OMe), 21.1 (CH₃, OAc), 17.79 ppm (CH₃, C-6). IR (CHCl₃): ν = 3690, 3603, 3018, 2935, 1734, 1220 cm^–1. MS (ESI) m/z (%) = 271 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₁H₂₀NaO₆ 271.1158; found 271.1167. Anal. calcd for C₁₁H₂₀O₆: C, 53.21; H, 8.12. Found: C, 52.92; H, 7.97.

Method D

Following the general procedure, starting from substrate 23 (62 mg, 0.16 mmol), after 2 h, a supplementary addition of n-Bu₃SnD (43 μL, 0.16 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 3:7) gave 56 (9.4 mg, 0.05 mmol, 31%), C-(4-O-acetyl-2,3-6-deoxy-di-O-methyl-β-d-(5-²H)altropyranosyl)methanol [(5-²H)57] (7.6 mg, 0.031 mmol, 19%), and C-(4-O-acetyl-2,3-di-O-methyl-α-d-[5-²H]fucopyranosyl)methanol (5-²H]58) (8.4 mg, 0.034 mmol, 21%, ²H/¹H 2.4:1) as colorless oils. Compound (5-²H)57: ¹H NMR (500 MHz, CDCl₃) δ_H 4.796 (d, J = 2.9 Hz, 1H, 4-H), 3.92–3.84 (m, 3H, 1-H, 2-H, 1’-H_b), 3.67 (m, 1H, 1’-H_a), 3.463 (s, 3H, OMe), 3.461 (s, 3H, OMe), 3.40 (dd, J = 3.5, 1.0 Hz, 1H, 3-H), 2.12 (s, 3H, OAc), 1.192 ppm (s, 3H, 6-H₃), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.2 (C, OAc), 77.7 (CH, C-3), 74.7 (CH, C-2), 74.2 (CH, C-1), 73.33 (CH, C-4), 69.26 (t, J_CD = 21.2 Hz, C, C-5), 62.7 (CH₂, C-1’), 59.3 (CH₃, OMe), 58.4 (CH₃, OMe), 21.1 (CH₃, OAc), 17.66 ppm (CH₃, C-6). MS (ESI) m/z (%) = 272 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₁H₁₉²HNaO₆ 272.1220; found 272.1219. Compound [5-²H]58: ¹H NMR (500 MHz, CDCl₃, only the deuterated product is described) δ_H 5.323 (d, J = 3.2 Hz, 1H, 4-H), 4.23 (m, 1H, 1-H), 3.91–3.83 (m, 2H, 1’-H₂), 3.70 (dd, J = 9.1, 6.0 Hz, 1H, 2-H), 3.50 (dd, J = 9.1, 3.5 Hz, 1H, 3-H), 3.50 (s, 3H, OMe), 3.42 (s, 3H, OMe), 2.17 (s, 3H, OAc), 1.169 ppm (s, 3H, 6-H₃), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only the deuterated product is described) δ_C 170.7 (C, OAc). 78.8 (CH, C-3), 77.1 (CH, C-2), 73.4 (CH, C-1), 69.46 (CH, C-4), 59.7 (CH₂, C-1’), 59.4 (CH₃, OMe), 57.5 (CH₃, OMe), 20.8 (CH₃, OAc), 16.37 ppm (CH₃, C-6). MS (ESI) m/z (%) = 272 (71) [M + Na]⁺, 271 (28) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₁H₁₉²HNaO₆ 272.1220; found 272.1222, [M + Na]⁺ calcd for C₁₁H₂₀NaO₆ 271.1158; found 271.1164.

Method E

Following the general procedure, starting from substrate 23 (126 mg, 0.32 mmol), after 2 h, a supplementary addition of n-Bu₃SnD (87 μL, 0.32 mmol) and BF₃•Et₂O (8 μL, 0.064 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 3:7) gave (5-²H)57 (9.5 mg, 0.038 mmol, 12%), [5-²H]58 (11.4 mg, 0.046 mmol, 14%, ²H/¹H 1:2), the unstable and volatile 2,7-anhydro-1,3-dideoxy-4,5-di-O-methyl-β-l-[3-²H]xylo-hept-2-ulopyranose ([4-²H]55) (13 mg, 0.069 mmol, 21%, ²H/¹H 5.4:1), and 3-O-acetyl-2,6-anhydro-1-deoxy-4,5-di-O-methyl-d-(6-²H)galactitol [(1-²H)60] (2 mg, 0.009 mmol, 3%) as colorless oils. Compound [4-²H]55: ¹H NMR (500 MHz, CDCl₃) δ_H 4.51 (ddd, J = 4.7, 4.7, 0.0 Hz, 1H, 1-H), 3.99 (dd, J = 7.6, 0.0 Hz, 1H, 1’-H_b), 3.74 (dd, J = 7.6, 5.4 Hz, 1H, 1’-H_a), 3.53–3.48 (m, 1H, 3-H), 3.48 (s, 3H, OMe), 3.40 (s, 3H, OMe), 3.35 (dd, J = 8.2, 4.1 Hz, 1H, 2-H), 2.33 (dd, J = 13.2, 6.7 Hz, 1H, 4-H_b), 2.32 (d, J = 6.6 Hz, 1H, 4-HD), 1.44 (m, 1H, 4-H_a), 1.49 ppm (s, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 107.0 (C, C-5), 80.7 (CH, C-2), 77.3 (CH, C-3), 73.5 (CH, C-1), 65.8 (CH₂, C-1’), 58.3 (CH₃, OMe), 57.1 (CH₃, OMe), 36.5 (CH₂, C-4 reduced product), 23.5 ppm (CH₃, C-6), expected triplet for C-4 was imperceptible for the deuterated product. IR (CHCl₃): ν = 3022, 2929, 1226 cm^–1. MS (ESI) m/z (%) = 212 (100) [M + Na]⁺, 211 (18) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₉H₁₅²HNaO₄ 212.1009; found 212.1015, [M + Na]⁺ calcd for C₉H₁₆NaO₄ 211.0946; found 211.0950. Compound (1-²H)60: [α]_D = −11.1 (c = 0.45, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 5.34 (dd, J = 3.4, 1.31 Hz, 1H, 4-H), 4.10 (br d, J = 4.4 Hz, 1H, 1-H), 3.58 (dddd, J = 6.6, 6.6, 6.6, 1.1 Hz, 1H, 5-H), 3.52 (m, 1H, 2-H), 3.50 (s, 3H, OMe), 3.43 (s, 3H, OMe), 3.24 (dd, J = 9.3, 3.4 Hz, 1H, 3-H), 2.18 (s, 3H, OAc), 1.17 ppm (d, J = 6.6 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.8 (C, OAc), 82.8 (CH, C-3), 75.4 (CH, C-2), 73.5 (CH, C-5), 69.4 (CH, C-4), 59.0 (CH₃, OMe), 57.4 (CH₃, OMe), 20.8 (CH₃, OAc), 16.8 ppm (CH₃, C-6), C-1 was imperceptible. IR (CHCl₃): ν = 3016, 2932, 1226 cm^–1. MS (ESI) m/z (%) = 242 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₀H₁₇²HNaO₅ 242.1115; found 242.1111.

Method F

Following the general procedure, starting from substrate 23 (13.9 mg, 0.035 mmol), all the starting material was consumed after 3 h. Chromatotron chromatography (hexanes–EtOAc, 4:6 to 0:1) gave 57 (1 mg, 0.004 mmol, 11%), 58 (2.2 mg, 0.09 mmol, 25%), and product 55 (0.7 mg, 0.004 mmol, 11%).

Method G

Following the general procedure, starting from substrate 23 (13.7 mg, 0.035 mmol), all the starting material was consumed after 3 h. Chromatotron chromatography (hexanes–EtOAc, 4:6 to 0:1) gave 57 (1.3 mg, 0.030 mmol, 15%), 58 (1.3 mg, 0.005 mmol, 15%), and product 55 (1.5 mg, 0.008 mmol, 23%).

Radical Reactions of 24

Method A

Following the general procedure, starting from substrate 24 (80.5 mg, 0.18 mmol), after 2 h, a supplementary addition of n-Bu₃SnH (50 μL, 0.18 mmol) was required. All the starting material was consumed after 3 h. Column chromatography (hexanes to hexanes–EtOAc, 4:6) gave 56 (23.6 mg, 0.126 mmol, 70%) and 59 (10.2 mg, 0.023 mmol, 13%).

Method C

Following the general procedure, starting from substrate 24 (62 mg, 0.11 mmol), after 2 h of reaction, a supplementary addition of TTMSS (33 μL, 0.11 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes–EtOAc, 6:4 to 3:7) gave 56 (12 mg, 0.064 mmol, 58%) and 59 (3.7 mg, 0.008 mmol, 8%).

Method D

Following the general procedure, starting from substrate 24 (50 mg, 0.086 mmol), after 2 h, a supplementary addition of n-Bu₃SnD (23 μL, 0.086 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 3:7) gave 56 (12 mg, 0.064 mmol, 58%) and 59 (7.2 mg, 0.016 mmol, 19%).

Method E

Following the general procedure, starting from substrate 24 (37.7 mg, 0.066 mmol), after 2 h, a supplementary addition of n-Bu₃SnD (17 μL, 0.066 mmol) and BF₃•Et₂O (2 μL, 0.016 mmol) was required. All the starting material was consumed after 4 h. Column chromatography (hexanes to hexanes–EtOAc, 3:7) gave 59 (4.2 mg, 0.009 mmol, 15%) and [4-²H]55 (5.1 mg, 0.027 mmol, 41%, ²H/¹H 3.1:1).

Method F

Following the general procedure, starting from substrate 24 (53 mg, 0.091 mmol), all the starting material was consumed after 2 h. Chromatotron chromatography (hexanes–EtOAc, 3:7) gave 59 (19.7 mg, 0.045 mmol, 49%).

Method G

Following the general procedure, starting from substrate 24 (61 mg, 0.105 mmol), all the starting material was consumed after 3 h. Chromatotron chromatography (hexanes–EtOAc, 3:7) gave 59 (22.9 mg, 0.052 mmol, 50%).

3-C-(3,4-Di-O-benzyl-α-l-fucopyranosyl)1-propene (75)

3-C-(2,3,4-Tri-O-benzyl-α-l-fucopyranosyl)1-propene (74)⁶¹ (1.56 g, 3.41 mmol) was dissolved in dry CH₂Cl₂ (68 mL) under a N₂ atmosphere, and I₂ (8.6 g, 34.1 mmol) was added. The mixture was stirred at room temperature for 3 h, and then it was poured over an aqueous solution of Na₂S₂O₃ and extracted with CH₂Cl₂. The combined extracts were dried over Na₂SO₄ and concentrated under reduced pressure. The resulting crude was dissolved in Et₂O/MeOH (1:1) (35 mL), and Zn dust (2.04 g, 31.2 mmol) and AcOH (357 μL) were subsequently added, with the mixture stirred overnight at room temperature. Then, it was filtered over Celite, evaporated, poured over a saturated aqueous solution of NaHCO₃, and extracted with CH₂Cl₂. The organic layers were dried over Na₂SO₄ and concentrated under reduced pressure. Column chromatography of the residue (hexanes–EtOAc, 8:2) gave 75 (791.8 mg, 2.15 mmol, 63%) as an amorphous solid: [α]_D = −57.1 (c = 0.42, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.35–7.24 (m, 10H, Ar), 5.81 (dddd, J = 17.1, 10.1, 6.7, 6.7 Hz, 1H, 2’-H), 5.10 (dd, J = 17.1, 1.0 Hz, 1H, 3’-H_b), 5.05 (dd, J = 10.1, 0.0 Hz, 1H, 3’-H_a), 4.78 (d, J = 12.0 Hz, 1H, OBn), 4.73 (d, J = 12.0 Hz, 1H, OBn), 4.59 (d, J = 12.0 Hz, 1H, OBn), 4.58 (d, J = 11.9 Hz, 1H, OBn), 4.11 (m, 1H, 1-H), 4.04 (br s, 1H, 2-H), 3.94 (m, 1H, 5-H), 3.77 (dd, J = 3.2, 3.2 Hz, 1H, 4-H), 3.73 (dd, J = 7.0, 2.9 Hz, 1H, 3-H), 2.33 (dd, J = 7.6, 7.6 Hz, 2H, 1’-H₂), 2.18 (br s, 1H, OH), 1.31 ppm (d, J = 6.6 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 138.4 (C, Ar), 138.3 (C, Ar), 135.0 (CH, C-2’), 128.4 (2 × CH, Ar), 128.3 (2 × CH, Ar), 127.7 (3 × CH, Ar), 127.6 (3 × CH, Ar), 116.7 (CH₂, C-3’), 78.8 (CH, C-3), 75.0 (CH, C-4), 73.0 (CH₂, OBn), 72.6 (CH₂, OBn), 70.8 (CH, C-1), 69.1 (CH, C-5), 68.9 (CH, C-2), 31.9 (CH₂, C-1’), 15.4 ppm (CH₃, C-6). IR (CHCl₃): ν = 3580, 3021, 1210 cm^–1. MS (ESI) m/z (%) = 391 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₃H₂₈NaO₄ 391.1885; found 391.1889.

3-C-(3,4-Di-O-benzylidene-α,β-d-arabinopyranosyl)1-propene (79 and 80)

Tetra-O-acetyl-d-arabinopyranose (78)⁶² (3.35 g, 10.54 mmol) was dissolved in dry CH₃CN (129 mL) under a N₂ atmosphere, and allyltrimethylsilane (9.8 mL, 61.51 mmol) and BF₃•Et₂O (6.2 mL, 49.2 mmol) were dropwise added at 0 °C. Then, the mixture was stirred at room temperature for 1.5 h. Subsequently, the solution was poured over a saturated aqueous solution of NaCl, extracted with EtOAc, dried over Na₂SO₄, and evaporated. Column chromatography of the residue (hexanes–EtOAc, 7:3) gave the allyl derivative (2.18 g, 7.27 mmol, 69%, 1S/1R isomers 6.8:1) as a colorless oil, which was subsequently dissolved in dry MeOH (34 mL), and Na₂CO₃ (1.23 g, 11.60 mmol) was added. The mixture was stirred at room temperature for 2.5 h, and then it was filtered, neutralized with the Amberlyst 15 H⁺ ion exchange resin, and evaporated. The crude was submitted to the benzylidene protection by treatment overnight with PhCH(OMe)₂ (1.5 mL, 10.91 mmol) and CSA (17 mg, 0.07 mmol) in dry DMF (7.3 mL) at room temperature under a N₂ atmosphere. The reaction was evaporated in a high vacuum rotovap and purified by column chromatography (hexanes–EtOAc, 8:2) to give 79 (228 mg, 0.87 mmol, 12%, d.r., 3:1) and 80 (780.8 g, 2.98 mmol, 41%, d.r., 3.5:1) as colorless oils. Compound 79: ¹H NMR (500 MHz, CDCl₃, only the major isomer is described) δ_H 7.48–7.34 (m, 5H, Ar), 6.23 (s, 1H, PhCH), 5.86 (dddd, J = 17.0, 10.1, 7.0, 7.0 Hz, 1H, 2’-H), 5.18 (dd, J = 17.0, 1.6 Hz, 1H, 3’-H_b), 5.13 (dd, J = 10.1, 1.6 Hz, 1H, 3’-H_a), 4.57 (ddd, J = 9.2, 6.7, 5.1 Hz, 1H, 4-H), 4.30 (dd, J = 5.1, 2.9 Hz, 1H, 3-H), 4.10 (dd, J = 12.0, 6.7 Hz, 1H, 5-H_b), 3.97 (br d, J = 5.4 Hz, 1H, 2-H), 3.73 (ddd, J = 7.9, 6.7, 1.6 Hz, 1H, 1-H), 3.55 (dd, J = 12.0, 9.1 Hz, 1H, 5-H_a), 2.48 (m, 1H, 1’-H_b), 2.36 ppm (m, 1H, 1’-H_a), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only the major isomer is described) δ_C 139.0 (C, Ar), 134.0 (CH, C-2’), 129.1 (CH, Ar), 128.4 (2 × CH, Ar), 125.9 (2 × CH, Ar), 117.6 (CH₂, C-3’), 103.3 (CH, PhCH), 75.7 (CH, C-3), 75.0 (CH, C-1), 70.1 (CH, C-4), 67.5 (CH, C-2), 60.0 (CH₂, C-5), 34.6 ppm (CH₂, C-1’). IR (CHCl₃): ν = 3567, 3452, 1643, 1457, 1100 cm^–1. MS (ESI) m/z (%) = 285 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₅H₁₈NaO₄ 285.1103; found 285.1099. Compound 80: ¹H NMR (500 MHz, CDCl₃, only the major isomer is described) δ_H 7.52–7.39 (m, 5H, Ar), 5.95 (s, 1H, PhCH), 5.84 (dddd, J = 17.4, 10.1, 7.3, 7.3 Hz, 1H, 2’-H), 5.18 (br d, J = 17.2 Hz, 1H, 3’-H_b), 5.11 (br d, J = 10.1 Hz, 1H, 3’-H_a), 4.43 (m, 1H, 4-H), 4.36 (dd, J = 5.7, 2.9 Hz, 1H, 3-H), 4.08 (dd, J = 12.0, 6.3 Hz, 1H, 5-H_b), 4.00 (dd, J = 2.5, 1.9 Hz, 1H, 2-H), 3.73 (ddd, J = 8.2, 6.6, 1.9 Hz, 1H, 1-H), 3.50 (dd, J = 12.0, 8.5 Hz, 1H, 5-H_a), 2.45 (m, 1H, 1’-H_b), 2.34 ppm (m, 1H, 1’-H_a), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only the major isomer is described) δ_C 137.1 (C, Ar), 134.0 (CH, C-2’), 129.1 (CH, Ar), 128.4 (2 × CH, Ar), 126.4 (2 × CH, Ar), 117.6 (CH₂, C-3’), 104.3 (CH, PhCH), 77.7 (CH, C-3), 75.0 (CH, C-1), 69.2 (CH, C-4), 68.0 (CH₂, C-5), 67.5 (CH, C-2), 34.8 ppm (CH₂, C-1’). IR (CHCl₃): ν = 3567, 3422, 3023, 1643, 1459, 1068 cm^–1. MS (ESI) m/z (%) = 285 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₅H₁₈NaO₄ 285.1103; found 285.1097.

3-C-(3,5-Di-O-tert-butyldiphenylsilyl-α-d-ribofuranosyl)1-propene (83)

To a solution of 3-C-(α-d-ribofuranosyl)1-propene (82)^56,57 (5.24 g, 30.11 mmol, 87%) in dry CH₂Cl₂ (145 mL) at 0 °C were sequentially added imidazole (3.07 g, 45.17 mmol) and DPSCl (7.72 mL, 30.11 mmol). The resulting mixture was stirred at 0 °C for 3 h, treated with saturated aqueous NH₄Cl, and extracted with CH₂Cl₂. Purification by column chromatography (hexanes–EtOAc, 97:3 to 6:4) afforded monoalcohol 83 (7.11 g, 10.94 mmol, 36%) and known diol 3-C-(5-O-tert-butyldiphenylsilyl-α-d-ribofuranosyl)1-propene (84)^13,57 (4.92 g, 11.94 mmol, 40%) as colorless oils. Compound 83: [α]_D = +33.1 (c = 0.58, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.57–7.15 (m, 20H, Ar), 5.77 (dddd, J = 17.0, 10.1, 7.0, 7.0 Hz, 1H, 2’-H), 5.04 (br d, J = 17.4 Hz, 1H, 3’-H_b), 4.97 (br d, J = 10.1 Hz, 1H, 3’-H_a), 4.49 (dd, J = 5.4, 5.4 Hz, 1H, 3-H), 3.87 (m, 1H, 4-H), 3.84 (m, 1H, 1-H), 3.77 (dd, J = 4.7, 4.7 Hz, 1H, 2-H), 3.50 (dd, J = 11.5, 2.2 Hz, 1H, 5-H_b), 3.14 (dd, J = 11.4, 3.2 Hz, 1H, 5-H_a), 2.76 (br s, 1H, OH), 2.38 (dd, J = 6.9, 6.9 Hz, 2H, 1’-H₂), 1.00 (s, 9H, ^tBu), 0.80 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 135.7 (2 × CH, Ar), 135.63 (2 × CH, Ar), 135.61 (CH, C-2’), 135.5 (2 × CH, Ar), 135.1 (2 × CH, Ar), 133.4 (C, Ar), 133.2 (C, Ar), 132.6 (C, Ar), 132.4 (C, Ar), 130.20 (CH, Ar), 130.16 (CH, Ar), 129.5 (2 × CH, Ar), 128.0 (2 × CH, Ar), 127.8 (2 × CH, Ar), 127.5 (4 × CH, Ar), 116.6 (CH₂, C-3’), 83.1 (CH, C-4), 81.0 (CH, C-1), 74.5 (CH, C-3), 72.7 (CH, C-2), 64.0 (CH₂, C-5), 34.1 (CH₂, C-1’), 26.9 (3 × CH₃, ^tBu), 26.7 (3 × CH₃, ^tBu), 19.2 (C, ^tBu), 19.0 ppm (C, ^tBu). IR (CHCl₃): ν = 3673, 3541, 2932, 2860, 1428, 1113 cm^–1. MS (ESI) m/z (%) = 673 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₅₀NaO₄Si₂ 673.3145; found 673.3141.

3-C-(3,5-Di-O-1,1,3,3-tetraisopropyldisiloxanyl-α-d-ribofuranosyl)1-propene (86)

1,3-Dichloro-1,1,3,3-tetraisopropyldisiloxane (1.1 mL, 3.44 mmol) was added to a stirred solution of triol 82(56,57) (300 mg, 1.72 mmol) in dry pyridine (53 mL) at 0 °C. The reaction mixture was stirred at room temperature for 20 h, and then the pyridine was evaporated under reduced pressure. The residue was poured over 10% HCl and extracted with EtOAc. The combined organic extracts were washed with a saturated solution of NaHCO₃, dried over Na₂SO₄, filtered, and evaporated. The crude was subjected to chromatography (hexanes–EtOAc, 95:5) to afford monoalcohol 86 (496.4 mg, 1.19 mmol, 69%) as a colorless oil: [α]_D = −17.6 (c = 0.51, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 5.86 (1H, dddd, J = 17.1, 10.1, 7.0, 7.0 Hz, 1H, 2’-H), 5.15 (br d, J = 17.1 Hz, 1H, 3’-H_b), 5.06 (br d, J = 10.1 Hz, 1H, 3’-H_a), 4.37 (dd, J = 7.3, 4.8 Hz, 1H, 3-H), 4.10 (dd, J = 4.4, 4.4 Hz, 1H, 2-H), 4.01–3.97 (m, 2H, 1-H, 5-H_b), 3.93 (ddd, J = 7.0, 7.0, 3.5 Hz, 1H, 4-H), 3.83 (dd, J = 11.7, 6.3 Hz, 1H, 5-H_a), 2.52 (ddd, J = 14.2, 6.9, 6.9 Hz, 1H, 1’-H_b), 2.42 (ddd, J = 14.5, 7.3, 7.3 Hz, 1H, 1’-H_a), 1.10–0.89 ppm (m, 28H, ⁱPr), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 134.6 (CH, C-2’), 117.1 (CH₂, C-3’), 80.5 (CH, C-1 or C-4), 80.3 (CH, C-1 or C-4), 74.9 (CH, C-3), 72.4 (CH, C-2), 63.4 (CH₂, C-5), 33.8 (CH₂, C-1’), 17.5 (CH₃, ⁱPr), 17.38 (CH₃, ⁱPr), 17.35 (2 × CH₃, ⁱPr), 17.2 (CH₃, ⁱPr), 17.1 (2 × CH₃, ⁱPr), 17.0 (CH₃, ⁱPr), 13.4 (CH, ⁱPr), 13.2 (CH, ⁱPr), 12.9 (CH, ⁱPr), 12.6 ppm (CH, ⁱPr). IR (CHCl₃): ν = 3671, 3540, 2949, 1732, 1643, 1465, 1120 cm^–1. MS (ESI) m/z (%) = 439 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₀H₄₀NaO₅Si₂ 439.2312; found 439.2310.

General Procedure of Hydroboration to Give 63, 66, 69, 72, 76, 81, 85, and 87

The corresponding allyl derivative (1 mmol) was dissolved in dry THF (10.5 mL). BH₃·THF 1 M complex (4 mL, 4 mmol) was added under a N₂ atmosphere at 0 °C, and then the reaction was stirred at room temperature for 1 h. At 0 °C, an aqueous solution of NaOH 3 M (20 mL) was dropwise added followed by H₂O₂ 30% (20 mL) and stirring was continued during 1 h at that temperature. The reaction was poured into brine and extracted with CH₂Cl₂. The organic layers were dried over Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography (hexanes–EtOAc) to give the corresponding alcohol.

3-C-(3,4,6-Tri-O-benzyl-α-d-glucopyranosyl)1-propanol (63)

Following the general procedure for the hydroboration, starting from 3-C-(3,4,6-tri-O-benzyl-α-d-glucopyranosyl)1-propene (62)⁵⁴ (700 mg, 1.48 mmol) and purification by column chromatography (hexanes–EtOAc, 8:2), the alcohol 63 (478 mg, 0.97 mmol, 66%) was obtained as a crystalline solid: mp 101.5–102.3 °C (n-hexane–EtOAc); [α]_D = +31.6 (c = 0.31, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.35–7.20 (m, 15H, Ar), 4.67 (d, J = 11.7 Hz, 1H, OBn), 4.63 (d, J = 11.4 Hz, 1H, OBn), 4.59 (d, J = 11.8 Hz, 1H, OBn), 4.54 (d, J = 12.2 Hz, 1H, OBn), 4.53 (d, J = 11.2 Hz, 1H, OBn), 4.50 (d, J = 12.1 Hz, 1H, OBn), 4.00 (ddd, J = 5.1, 5.1, 5.1 Hz, 1H, 5-H), 3.90 (ddd, J = 9.5, 3.2, 3.2 Hz, 1H, 1-H), 3.79 (dd, J = 10.1, 6.0 Hz, 1H, 6-H_b), 3.73 (dd, J = 5.8, 5.8 Hz, 1H, 3-H), 3.68–3.61 (m, 4H, 3’-H₂, 2-H, 6-H_a), 3.58 (dd, J = 5.4, 5.4 Hz, 1H, 4-H), 2.96 (br s, 1H, OH), 2.15 (br s, 1H, OH), 1.80–1.61 ppm (m, 4H, 1’-H₂, 2’-H₂). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 138.0 (2 × C, Ar), 137.4 (C, Ar), 127.6–128.5 (15 × CH, Ar), 78.1 (CH, C-3), 75.2 (CH, C-4), 73.5 (CH₂, OBn), 73.3 (CH₂, OBn), 73.3 (CH, C-5), 73.0 (CH₂, OBn), 71.9 (CH, C-1), 70.0 (CH, C-2), 68.2 (CH₂, C-6), 62.6 (CH₂, C-3’), 29.2 (CH₂, C-2’), 24.8 ppm (CH₂, C-1’), IR (CHCl₃): ν = 3496, 2938, 1455, 1086 cm^–1. MS (ESI) m/z (%) = 515 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₀H₃₆NaO₆ 515.2410; found 515.2407. Anal. calcd for C₃₀H₃₆O₆: C, 73.15; H, 7.37. Found: C, 72.90; H, 7.26.

3-C-(3,4,6-Tri-O-benzyl-β-d-glucopyranosyl)1-propanol (66)

Following the general procedure for the hydroboration, starting from 3-C-(3,4,6-tri-O-benzyl-β-d-glucopyranosyl)1-propene (65)^50c (103 mg, 0.22 mmol) and purification by column chromatography (hexanes–EtOAc, 7:3), the alcohol 66 (77.3 mg, 0.16 mmol, 73%) was obtained as a crystalline solid: mp 112.0–112.7 °C (n-hexane–EtOAc); [α]_D = +35.7 (c = 0.63, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.28–7.18 (m, 13H, Ar), 7.12–7.10 (m, 2H, Ar), 4.88 (d, J = 11.6 Hz, 1H, OBn), 4.71 (d, J = 10.8 Hz, 1H, OBn), 4.67 (d, J = 11.7 Hz, 1H, OBn), 4.53 (d, J = 12.2 Hz, 1H, OBn), 4.49 (d, J = 10.8 Hz, 1H, OBn), 4.45 (d, J = 12.1 Hz, 1H, OBn), 3.61 (ddd, J = 10.8, 10.8, 2.2 Hz, 1H, 5-H), 3.58–3.55 (m, 3H, 3’-H₂, 6-H_b), 3.51 (dd, J = 9.3, 9.3 Hz, 1H, 4-H), 3.39 (dd, J = 8.9, 8.9 Hz, 1H, 3-H), 3.37 (m, 1H, 6-H_a), 3.26 (dd, J = 9.2, 9.2 Hz, 1H, 2-H), 3.15 (ddd, J = 8.5, 8.5, 2.4 Hz, 1H, 1-H), 2.22 (br s, 2H, 2 × OH), 1.92 (m, 1H, 1’-H_b), 1.68–1.62 (m, 2H, 2’-H₂), 1.49 ppm (dddd, J = 7.7, 7.7, 7.7, 7.7 Hz, 1H, 1’-H_a), ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 138.6 (C, Ar), 138.0 (2 × C, Ar), 128.6 (2 × CH, Ar), 128.4 (2 × CH, Ar), 128.3 (2 × CH, Ar), 127.89 (3 × CH, Ar), 127.84 (2 × CH, Ar), 127.79 (2 × CH, Ar), 127.75 (CH, Ar), 127.6 (CH, Ar), 86.8 (CH, C-3), 79.4 (CH, C-4), 78.8 (CH, C-5), 78.4 (CH, C-1), 75.2 (CH₂, OBn), 74.7 (CH₂, OBn), 73.7 (CH, C-2), 73.5 (CH₂, OBn), 69.0 (CH₂, C-6), 62.7 (CH₂, C-3’), 28.8 (CH₂, C-2’), 28.5 ppm (CH₂, C-1’). IR (CHCl₃): ν = 3588, 3500, 2928, 1455, 1052 cm^–1. MS (ESI) m/z (%) = 515 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₀H₃₆NaO₆ 515.2410; found 515.2412.

3-C-(3,4,6-Tri-O-benzyl-α-d-mannopyranosyl)1-propanol (69)

Following the general procedure for the hydroboration, starting from 3-C-(3,4,6-tri-O-benzyl-α-d-mannopyranosyl)1-propene (68)^54,63 (675.6 mg, 1.42 mmol) and purification by column chromatography (hexanes–EtOAc, 1:1 to 3:7), the alcohol 69 (368.4 mg, 0.75 mmol, 53%) was obtained as an amorphous solid: [α]_D = +34.0 (c = 0.45, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.35–7.25 (m, 13H, Ar), 7.22–7.20 (m, 2H, Ar), 4.71 (d, J = 11.1 Hz, 1H, OBn), 4.61 (d, J = 11.7 Hz, 1H, OBn), 4.57 (d, J = 10.1 Hz, 1H, OBn), 4.55 (d, J = 11.1 Hz, 1H, OBn), 4.52 (d, J = 11.4 Hz, 1H, OBn), 4.51 (d, J = 12.0 Hz, 1H, OBn), 3.89 (m, 1H, 1-H), 3.82–3.80 (m, 2H, 2-H, 3-H), 3.77–3.75 (m, 2H, 4-H, 5-H), 3.70 (dd, J = 10.1, 5.4 Hz, 1H, 6-H_b), 3.68–3.60 (m, 3H, 3’-H₂, 6-H_a), 2.25 (br s, 2H, 2 × OH), 1.76–1.59 ppm (m, 4H, 1’-H₂, 2’-H₂). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 138.1 (2 × C, Ar), 137.6 (C, Ar), 127.6–128.6 (15 × CH, Ar), 79.2 (CH, C-3), 75.1 (CH, C-1), 74.2 (CH, C-5), 74.0 (CH₂, OBn), 73.4 (CH₂, OBn), 72.8 (CH, C-4), 72.3 (CH₂, OBn), 69.4 (CH, C-2), 69.0 (CH₂, C-6), 62.2 (CH₂, C-3’), 29.2 (CH₂, C-2’), 25.8 ppm (CH₂, C-1’). IR (CHCl₃): ν = 3562, 3500, 2933, 1094 cm^–1. MS (ESI) m/z (%) = 515 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₀H₃₆NaO₆ 515.2410; found 515.2403. Anal. calcd for C₃₀H₃₆O₆: C, 78.15; H, 7.87. Found C, 78.07; H, 7.60.

3-C-(3,4,6-Tri-O-benzyl-β-d-mannopyranosyl)1-propanol (72)

Following the general procedure for the hydroboration, starting from 3-C-(3,4,6-tri-O-benzyl-β-d-mannopyranosyl)1-propene (71)^54,63 (106 mg, 0.22 mmol) and purification by column chromatography (hexanes–EtOAc, 7:3), the alcohol 72 (72.6 mg, 0.15 mmol, 67%) was obtained as a colorless oil: [α]_D = +2.1 (c = 0.48, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.37–7.17 (m, 15H, Ar), 4.83 (d, J = 10.8 Hz, 1H, OBn), 4.71 (d, J = 11.6 Hz, 1H, OBn), 4.64 (d, J = 11.7 Hz, 1H, OBn), 4.57 (d, J = 12.1 Hz, 1H, OBn), 4.52 (d, J = 12.1 Hz, 1H, OBn), 4.49 (d, J = 10.8 Hz, 1H, OBn), 3.90 (dd, J = 2.9, 0.0 Hz, 1H, 2-H), 3.74 (dd, J = 9.6, 9.6 Hz, 1H, 4-H), 3.70 (dd, J = 8.0, 1.6 Hz, 1H, 6-H_b), 3.63 (m, 3H, 6-H_a, 3’-H₂), 3.57 (dd, J = 9.0, 3.2 Hz, 1H, 3-H), 3.40 (ddd, J = 9.8, 5.4, 1.9 Hz, 1H, 5-H), 3.35 (ddd, J = 9.2, 3.8, 0.0 Hz, 1H, 1-H), 2.94 (br s, 2H, 2 × OH), 1.88 (m, 1H, 1’-H_b), 1.75–1.64 ppm (m, 3H, 1’-H_a, 2’-H₂). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 138.2 (C, Ar), 138.1 (C, Ar), 137.8 (C, Ar), 127.6–128.5 (15 × CH, Ar), 83.4 (CH, C-3), 79.0 (CH, C-1), 78.1 (CH, C-5), 75.1 (CH₂, OBn), 74.7 (CH, C-4), 73.4 (CH₂, OBn), 71.6 (CH₂, OBn), 69.4 (CH₂, C-6), 68.7 (CH, C-2), 62.6 (CH₂, C-3’), 29.4 (CH₂, C-2’), 28.0 ppm (CH₂, C-1’). IR (CHCl₃): ν = 3461, 2869, 1455, 1093 cm^–1. MS (ESI) m/z (%) = 515 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₀H₃₆NaO₆ 515.2410; found 515.2403. Anal. calcd for C₃₀H₃₆O₆: C, 73.15; H, 7.37. Found: C, 73.36; H, 7.67.

3-C-(3,4-Di-O-benzyl-α-l-fucopyranosyl)1-propanol (76)

Following the general procedure for the hydroboration, starting from 75 (744.3 mg, 2.02 mmol) and purification by column chromatography (hexanes–EtOAc, 2:8), the alcohol 76 (442.9 mg, 1.15 mmol, 57%) was obtained as a colorless oil: [α]_D = −51.4 (c = 0.52, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.35–7.25 (m, 10H, Ar), 4.78 (d, J = 11.7 Hz, 1H, OBn), 4.75 (d, J = 11.7 Hz, 1H, OBn), 4.60 (d, J = 11.7 Hz, 1H, OBn), 4.58 (d, J = 11.7 Hz, 1H, OBn), 4.07–4.06 (m, 2H, 1-H, 2-H), 3.91 (m, 1H, 5-H), 3.76 (dd, J = 3.2, 3.2 Hz, 1H, 4-H), 3.71 (dd, J = 6.6, 2.5 Hz, 1H, 3-H), 3.67–3.61 (m, 2H, 3’-H₂), 2.40 (br s, 1H, OH), 2.21 (br s, 1H, OH), 1.69–1.62 (m, 4H, 1’-H₂, 2’-H₂), 1.31 ppm (d, J = 6.6 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 138.4 (C, Ar), 138.2 (C, Ar), 128.5 (2 × CH, Ar), 128.3 (2 × CH, Ar), 127.7 (3 × CH, Ar), 127.6 (3 × CH, Ar), 79.0 (CH, C-3), 75.1 (CH, C-4), 73.2 (CH₂, OBn), 72.6 (CH₂, OBn), 71.8 (CH, C-1 or C-2), 69.1 (CH, C-5), 68.9 (CH, C-1 or C-2), 62.6 (CH₂, C-3’), 23.6 (2 × CH₂, C-1’, C-2’), 15.6 ppm (CH₃, C-6). IR (CHCl₃): ν = 3585, 3422, 3016, 1228 cm^–1. MS (ESI) m/z (%) = 409 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₃H₃₀NaO₅ 409.1991; found 409.1990.

3-C-(3,4-Di-O-benzylidene-α,β-d-arabinopyranosyl)1-propanol (81)

Following the general procedure for the hydroboration, starting from 79 (180 mg, 0.69 mmol) and purification by column chromatography (hexanes–EtOAc, 2:8), the alcohol 81 (106.1 mg, 0.38 mmol, 55%) was obtained as a colorless oil: ¹H NMR (500 MHz, CDCl₃, only the major 1S isomer is described) δ_H 7.47–7.37 (m, 5H, Ar), 6.22 (br s, 1H, PhCH), 4.57 (ddd, J = 8.9, 6.4, 5.1 Hz, 1H, 4-H), 4.29 (dd, J = 5.1, 2.3 Hz, 1H, 3-H), 4.08 (dd, J = 11.7, 6.6 Hz, 1H, 5-H_b), 3.95 (br s, 1H, 2-H), 3.70–3.66 (m, 3H, 3’-H₂, 1-H), 3.54 (dd, J = 11.7, 8.8 Hz, 1H, 5-H_a), 2.5 (br s, 1H, OH), 2.66 (br s, 1H, OH), 1.82–1.66 ppm (m, 4H, 1’-H₂, 2’-H₂). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only the major 1S isomer is described) δ_C 139.0 (C, Ar), 129.1 (CH, Ar), 128.4 (2 × CH, Ar), 125.9 (2 × CH, Ar), 103.3 (CH, PhCH), 75.7 (CH, C-1 or C-3), 75.6 (CH, C-1 or C-3), 70.1 (CH, C-4), 68.0 (CH, C-2), 65.9 (CH₂, C-5), 62.6 (CH₂, C-3’), 28.9 (CH₂, C-1’ or C-2’), 26.7 ppm (CH₂, C-1’ or C-2’). IR (CHCl₃): ν = 3613, 3417, 2927, 1208, 1070 cm^–1. MS (ESI) m/z (%) = 303 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₅H₂₀NaO₅ 303.1208; found 303.1203.

3-C-(3,5-Di-O-tert-butyldiphenylsilyl-α-d-ribofuranosyl)1-propanol (85)

The general procedure for the hydroboration starting from 83 (3.55 g, 5.46 mmol) but adding dropwise at 0 °C an aqueous saturated solution of NaHCO₃ (35.5 mL) instead of the NaOH solution followed by H₂O₂ 30% (18 mL) gave, after purification by column chromatography (hexanes–EtOAc, 97:3 to 7:3), the alcohol 85 (1.28 mg, 1.92 mmol, 35%) as a colorless oil: [α]_D = +23.0 (c = 0.64, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.65–7.26 (m, 20H, Ar), 4.53 (dd, J = 5.4, 5.4 Hz, 1H, 3-H), 3.97 (m, 1H, 4-H), 3.88 (m, 1H, 1-H), 3.82 (dd, J = 5.1, 5.1 Hz, 1H, 2-H), 3.71–3.62 (m, 2H, 3’-H₂), 3.57 (dd, J = 11.4, 2.2 Hz, 1H, 5-H_b), 3.25 (dd, J = 11.4, 3.8 Hz, 1H, 5-H_a), 1.82–1.77 (m, 2H, 1’-H₂), 1.71–1.66 (m, 2H, 2’-H₂), 1.61 (br s, 2H, OH), 1.08 (s, 9H, ^tBu), 0.91 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 135.67 (2 × CH, Ar), 135.62 (2 × CH, Ar), 135.58 (2 × CH, Ar), 135.53 (2 × CH, Ar), 133.3 (C, Ar), 133.2 (C, Ar), 132.5 (C, Ar), 132.3 (C, Ar), 130.25 (CH, Ar), 130.20 (CH, Ar), 129.5 (2 × CH, Ar), 128.0 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.6 (4 × CH, Ar), 83.0 (CH, C-4), 81.5 (CH, C-1), 74.6 (CH, C-3), 73.0 (CH, C-2), 64.0 (CH₂, C-5), 62.8 (CH₂, C-3’), 29.6 (CH₂, C-2’), 26.9 (3 × CH₃, ^tBu), 26.7 (3 × CH₃, ^tBu), 26.1 (CH₂, C-1’), 19.2 (C, ^tBu), 19.1 ppm (C, ^tBu). IR (CHCl₃): ν = 3532, 2932, 1428, 1206, 1113 cm^–1. MS (ESI) m/z (%) = 691 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₅₂NaO₅Si₂ 691.3251; found 691.3250.

3-C-(3,5-Di-O-1,1,3,3-tetraisopropyldisiloxanyl-α-d-ribofuranosyl)1-propanol (87)

The general procedure for the hydroboration starting from 86 (228 mg, 0.55 mmol) but adding dropwise at 0 °C an aqueous saturated solution of NaHCO₃ (3.1 mL) instead of the NaOH solution followed by H₂O₂ 30% (1.6 mL) gave, after purification by column chromatography (hexanes–EtOAc, 1:1), the alcohol 87 (150.47 mg, 0.35 mmol, 63%) as a colorless oil: [α]_D = −10.8 (c = 0.62, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 4.38 (dd, J = 7.3, 4.8 Hz, 1H, 3-H), 5.00 (dd, J = 4.7, 4.7 Hz, 1H, 2-H), 4.00–3.96 (m, 2H, 1-H, 5-H_b), 3.91 (ddd, J = 7.3, 7.3, 3.5 Hz, 1H, 4-H), 3.64 (dd, J = 12.0, 6.3 Hz, 1H, 5-H_a), 3.69–3.63 (m, 2H, 3’-H₂), 2.23 (br s, 2H, OH), 1.84 (ddd, J = 14.2, 7.6, 7.6 Hz, 1H, 1’-H_b), 1.79–1.64 (m, 3H, 1’-H_a, 2’-H₂), 1.11–0.95 ppm (m, 28H, ⁱPr). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 80.8 (CH, C-1), 80.3 (CH, C-4), 74.8 (CH, C-3), 72.8 (CH, C-2), 63.2 (CH₂, C-5), 62.7 (CH₂, C-3’), 29.3 (CH₂, C-2’), 25.8 (CH₂, C-1’), 17.4 (CH₃, ⁱPr), 17.33 (CH₃, ⁱPr), 17.30 (2 × CH₃, ⁱPr), 17.19 (CH₃, ⁱPr), 17.02 (2 × CH₃, ⁱPr), 16.93 (CH₃, ⁱPr), 13.4 (CH, ⁱPr), 13.2 (CH, ⁱPr), 12.8 (CH, ⁱPr), 12.6 ppm (CH, ⁱPr). IR (CHCl₃): ν = 3622, 3528, 2948, 2870, 1465, 1041 cm^–1. MS (ESI) m/z (%) = 457 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₀H₄₂NaO₆Si₂ 457.2418; found 457.2413.

General Procedure for the Mitsunobu Reaction to Give Phthalimide Derivatives 11, 13, 14, 64, 67, 70, 73, 77, and 88

DEAD (449 μL, 2.58 mmol) was added dropwise to a stirred solution of the alcohol (1 mmol), N-hydroxyphthalimide (420 mg, 2.58 mmol), and PPh₃ (670 mg, 2.58 mmol) in dry THF (10.3 mL), and the resulting solution was stirred at 0 °C for 1–4 h. Then, the solvent was removed and the crude was quenched with water and extracted with CHCl₃. The combined extracts were dried over Na₂SO₄ and concentrated under reduced pressure. Column chromatography of the residue (hexanes–EtOAc) gave the corresponding phthalimide.

3-C-(3,4-Di-O-benzylidene-2-O-diphenoxyphosphoryl-α,β-d-arabinopyranosyl)1-propoxyphthalimide (11)

Following the general procedure starting from alcohol 81 (95.2 mg, 0.34 mmol) stirring at 0 °C for 0.5 h, after purification by column chromatography (hexanes–EtOAc, 6:4), a phthalimide intermediate (202.4 mg) was obtained as a yellow oil. The crude (202.4 mg) was dissolved in dry CH₂Cl₂ (10.2 mL) under a N₂ atmosphere. ClPO(OPh)₂ (324 μL, 1.6 mmol) and DMAP (195.5 mg, 1.6 mmol) were added at 0 °C, and after 5 min, the mixture was stirred at room temperature for 1.5 h. The reaction was quenched with a saturated aqueous NH₄Cl solution and extracted with CH₂Cl₂. The organic extracts were dried over Na₂SO₄ and concentrated under reduced pressure. Column chromatography of the residue (PhCH₃–EtOAc, 9:1) gave 11 (149.4 mg, 0.23 mmol, 67%, 1S/1R 4.7:1) as a colorless oil. ¹H NMR (500 MHz, CDCl₃, only the major 1S isomer is described, simulated ring coupling constants using DAISY) δ_H 7.84–7.81 (m, 2H, Ar), 7.75–7.72 (m, 2H, Ar), 7.40–7.14 (m, 15H, Ar), 6.20 (s, 1H, PhCH), 4.88 (ddd, J = 3.3, 2.0 Hz, ³J_PH = 9.2 Hz, 1H, 2-H), 4.38 (ddd, J = 7.9, 6.0, 5.2 Hz, 1H, 4-H), 4.32 (dd, J = 5.2, 3.3 Hz, 1H, 3-H), 4.13 (ddd, J = 6.7, 6.7, 1.3 Hz, 2H, 3’-H₂), 4.04 (dd, J = 12.2, 6.0 Hz, 1H, 5-H_b), 3.83 (m, 1H, 1-H), 3.59 (dd, J = 12.2, 7.9 Hz, 1H, 5-H_a), 1.92 (m, 1H, 2’-H_b), 1.85–1.76 (m, 2H, 1’-H_b, 2’-H_a), 1.67 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, only the major 1S isomer is described) δ_C 163.6 (2 × C, CO), 150.4 (d, ²J_PC = 8.4 Hz, C, Ar), 150.3 (d, ²J_PC = 7.4 Hz, C, Ar), 138.6 (C, Ar), 134.4 (2 × CH, Ar), 129.9 (2 × CH, Ar), 129.8 (2 × CH, Ar), 129.1 (2 × C, Ar), 129.0 (CH, Ar), 128.4 (2 × CH, Ar), 126.0 (2 × CH, Ar), 125.58 (CH, Ar), 125.55 (CH, Ar), 123.5 (2 × CH, Ar), 120.2 (2 × CH, Ar), 120.1 (2 × CH, Ar), 103.4 (CH, PhCH), 77.9 (CH₂, C-3’), 75.3 (d, ²J_PC = 6.3 Hz, CH, C-2), 73.6 (d, ³J_PC = 5.3 Hz, CH, C-1 or C-3), 73.5 (d, ³J_PC = 2.1 Hz, CH, C-1 or C-3), 70.5 (CH, C-4), 64.6 (CH₂, C-5), 25.8 (CH₂, C-1’), 24.5 ppm (CH₂, C-2’). IR (CHCl₃): ν = 3018, 1791, 1734, 1226 cm^–1. MS (ESI) m/z (%) = 680 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₅H₃₂NNaO₁₀P 680.1662; found 680.1661. Anal. calcd for C₃₅H₃₂NO₁₀P: C, 63.92; H, 4.90: N, 2.13. Found: C, 64.10; H, 5.16; N, 2.33.

3-C-(2-O-Acetyl-3,5-di-O-tert-butyldiphenylsilyl-α-d-ribofuranosyl)1-propoxyphthalimide (13)

Following the general procedure starting from alcohol 85 (604 mg, 0.90 mmol) and stirring at 50 °C for 2 h, after purification by column chromatography (hexanes–EtOAc, 8:2), a phthalimide intermediate was obtained (715.4 mg, 0.88 mmol, 98%) as a colorless oil. Phthalimide (715.4 mg, 0.88 mmol) was dissolved in dry pyridine (3.4 mL), and Ac₂O (1.15 mL) and DMAP (1.1 mg, 9.0·10^–3 mmol) were added. The reaction was stirred at room temperature for 1 h, and then it was evaporated in a high vacuum rotovap, quenched with an aqueous solution of HCl 10%, and extracted with CH₂Cl₂. The combined organic extracts were dried over Na₂SO₄ and concentrated under reduced pressure. Column chromatography of the residue (hexanes–EtOAc, 8:2) gave 13 (589.9 mg, 0.69 mmol, 78%) as a white solid. mp 42.3–43.7 °C (n-hexane–EtOAc); [α]_D = +33.2 (c = 0.76, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.82–7.71 (m, 4H, Ar), 7.67–7.27 (m, 20H, Ar), 5.17 (dd, J = 4.7, 3.4 Hz, 1H, 2-H), 4.64 (dd, J = 6.7, 4.7 Hz, 1H, 3-H), 4.22–4.17 (m, 2H, 3’-H₂), 4.03–3.98 (m, 2H, 1-H, 4-H), 3.61 (dd, J = 11.4, 2.2 Hz, 1H, 5-H_b), 3.31 (dd, J = 11.4, 3.2 Hz, 1H, 5-H_a), 2.15 (s, 3H, OAc), 1.95 (m, 1H, 2’-H_b), 1.81–1.68 (m, 3H, 1’-H₂, 2’-H_a), 1.04 (s, 9H, ^tBu), 0.90 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.4 (C, OAc), 163.6 (2 × C, CO), 135.84 (2 × CH, Ar), 135.79 (2 × CH, Ar), 135.64 (2 × CH, Ar), 135.59 (2 × CH, Ar), 134.4 (2 × CH, Ar), 133.5 (C, Ar), 133.4 (C, Ar), 133.3 (C, Ar), 132.8 (C, Ar), 129.98 (CH, Ar), 129.95 (CH, Ar), 129.5 (2 × CH, Ar), 129.0 (2 × C, Ar), 127.78 (2 × CH, Ar), 127.74 (2 × CH, Ar), 127.57 (2 × CH, Ar), 127.55 (2 × CH, Ar), 123.5 (2 × CH, Ar), 82.8 (CH, C-4), 79.0 (CH, C-1), 78.3 (CH₂, C-3’), 74.9 (CH, C-2), 72.8 (CH, C-3), 63.6 (CH₂, C-5), 26.8 (3 × CH₃, ^tBu), 26.7 (3 × CH₃, ^tBu), 26.1 (CH₂, C-1’), 25.0 (CH₂, C-2’), 21.0 (CH₃, OAc), 19.2 (C, ^tBu), 19.1 ppm (C, ^tBu). IR (CHCl₃): ν = 2932, 2860, 1791, 1731, 1428, 1242, 1113 cm^–1. MS (ESI) m/z (%) = 878 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₅₀H₅₇NNaO₈Si₂ 878.3520; found 878.3530.

3-C-(3,5-Di-O-tert-butyldiphenylsilyl-2-O-trifluoromethylsulfonyl-α-d-ribofuranosyl)1-propoxyphthalimide (14)

Following the general procedure starting from alcohol 85 (604 mg, 0.90 mmol) and stirring at 50 °C for 2 h, after purification by column chromatography (hexanes–EtOAc, 8:2), a phthalimide intermediate was obtained (715.4 mg, 0.88 mmol, 98%) as a colorless oil. Phthalimide (715.4 mg, 0.88 mmol) was dissolved in dry pyridine (0.26 mL), and Tf₂O (22 μL, 0.13 mmol) was added. The reaction was stirred at room temperature for 1 h, and then it was evaporated in a high vacuum rotovap, quenched with an aqueous solution of HCl 10%, and extracted with CH₂Cl₂. The combined organic extracts were dried over Na₂SO₄ and concentrated under reduced pressure. Column chromatography of the residue (hexanes–EtOAc, 8:2) gave 14 (48.4 mg, 0.051 mmol, 78%) as a white solid. mp 42.6–43.9 °C (n-hexane–EtOAc); [α]_D = +20.8 (c = 0.63, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.44–7.42 (m, 4H, Ar), 7.41–7.24 (m, 20H, Ar), 5.30 (dd, J = 4.6, 4.1 Hz, 1H, 2-H), 4.71 (dd, J = 5.7, 4.6 Hz, 1H, 3-H), 4.25–4.16 (m, 3H, 1-H, 3’-H₂), 3.95 (m, 1H, 4-H), 3.35 (dd, J = 11.6, 2.0 Hz, 1H, 5-H_b), 2.76 (dd, J = 11.6, 3.1 Hz, 1H, 5-H_a), 2.05–1.92 (m, 3H, 1’-H₂ or 2’-H₂, 1’-H_b or 2’-H_b), 1.82 (dddd, J = 12.9, 12.9, 6.3, 6.3 Hz, 1H, 1’-H_a or 2’-H_a), 1.06 (s, 9H, ^tBu), 0.85 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.5 (2 × C, CO), 135.9 (2 × CH, Ar), 135.8 (2 × CH, Ar), 135.5 (4 × CH, Ar), 134.4 (2 × CH, Ar), 133.2 (C, Ar), 133.03 (C, Ar), 132.97 (C, Ar), 131.6 (C, Ar), 130.13 (CH, Ar), 130.06 (CH, Ar), 129.58 (CH, Ar), 129.56 (CH, Ar), 129.0 (2 × C, Ar), 127.9 (2 × CH, Ar), 127.7 (2 × CH, Ar), 127.55 (4 × CH, Ar), 123.5 (2 × CH, Ar), 89.3 (CH, C-2), 82.6 (CH, C-4), 77.84 (CH, C-1), 77.81 (CH₂, C-3’), 73.1 (CH, C-3), 63.5 (CH₂, C-5), 26.65 (3 × CH₃, ^tBu), 26.63 (3 × CH₃, ^tBu), 25.9 (CH₂, C-1’ or C-2’), 24.8 (CH₂, C-1’ or C-2’), 19.2 (C, ^tBu), 19.0 ppm (C, ^tBu), 1C from CF₃ group is missing. IR (CHCl₃): ν = 2932, 1791, 1734, 1113 cm^–1. MS (ESI) m/z (%) = 968 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₉H₅₄F₃NNaO₉SSi₂ 968.2908; found 968.2907. Anal. calcd for C₄₉H₅₄F₃NO₉SSi₂: C, 62.20; H, 5.75; N, 1.48; S, 3.39. Found: C, 62.11; H, 5.97; N, 1.52; S, 3.19.

3-C-(3,4,6-Tri-O-benzyl-α-d-glucopyranosyl)1-propoxyphthalimide (64)

Following the general procedure starting from alcohol 63 (85.6 mg, 0.18 mmol) and purification by column chromatography (hexanes–Et₂O, 1:1), product 64 (107 mg, 0.17 mmol, 93%) was obtained as a colorless oil: [α]_D = +12.3 (c = 0.26, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.82–7.71 (m, 4H, Ar), 7.34–7.21 (m, 15H, Ar), 4.69 (d, J = 11.5 Hz, 1H, OBn), 4.63 (d, J = 11.4 Hz, 1H, OBn), 4.62 (d, J = 11.7 Hz, 1H, OBn), 4.56 (d, J = 12.4 Hz, 1H, OBn), 4.56 (d, J = 12.4 Hz, 1H, OBn), 4.48 (d, J = 12.0 Hz, 1H, OBn), 4.26–4.21 (m, 2H, 3’-H₂), 4.02–3.96 (m, 2H, 1-H, 2-H), 3.82 (dd, J = 10.2, 5.7 Hz, 1H, 6-H_b), 3.77 (dd, J = 5.8, 5.8 Hz, 1H, 4-H), 3.73–3.68 (m, 2H, 5-H, 6-H_a), 3.63 (dd, J = 5.3, 5.3 Hz, 1H, 3-H), 1.99–1.76 ppm (m, 4H, 1’-H₂, 2’-H₂), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 163.6 (2 × C, CO), 138.1 (2 × C, Ar), 137.5 (C, Ar), 134.3 (2 × CH, Ar), 129.0 (2 × C, Ar), 128.5 (2 × CH, Ar), 128.4 (2 × CH, Ar), 128.3 (2 × CH, Ar), 127.84 (3 × CH, Ar), 127.79 (CH, Ar), 127.7 (2 × CH, Ar), 127.58 (2 × CH, Ar), 127.56 (CH, Ar), 123.4 (2 × CH, Ar), 78.3 (CH₂, C-3’), 78.1 (CH, C-3), 75.3 (CH, C-4), 73.5 (CH₂, OBn), 73.3 (CH₂, OBn), 73.3 (CH, C-5), 72.9 (CH₂, OBn), 71.4 (CH, C-1), 69.8 (CH, C-2), 68.3 (CH₂, C-6), 24.5 (CH₂, C-1’), 24.3 ppm (CH₂, C-2’). IR (CHCl₃): ν = 3514, 2935, 2871, 1792, 1737, 1372, 1083 cm^–1. MS (E/I 70 eV): m/z (%) = 546 (6) [M – C₇H₇]⁺, 529 (51) [M – C₇H₈O]⁺, 91 (100) [C₇H₇]⁺. HRMS (E/I): m/z: [M – C₇H₈O]⁺ calcd for C₃₁H₃₁NO₇ 529.2101; found 529.2122.

3-C-(3,4,6-Tri-O-benzyl-β-d-glucopyranosyl)1-propoxyphthalimide (67)

Following the general procedure starting from alcohol 66 (810 mg, 1.64 mmol) and purification by column chromatography (hexanes–EtOAc, 1:1), product 67 (790 mg, 1.24 mmol, 76%) was obtained as a colorless oil: [α]_D = +14.5 (c = 0.53, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.82–7.79 (m, 2H, Ar), 7.75–7.72 (m, 2H, Ar), 7.37–7.18 (m, 15H, Ar), 4.95 (d, J = 11.6 Hz, 1H, OBn), 4.80 (d, J = 11.0 Hz, 1H, OBn), 4.80 (d, J = 11.0 Hz, 1H, OBn), 4.61 (d, J = 12.2 Hz, 1H, OBn), 4.58 (d, J = 10.7 Hz, 1H, OBn), 4.53 (d, J = 12.3 Hz, 1H, OBn), 4.24 (ddd, J = 9.5, 6.6, 1.2 Hz, 2H, 3’-H₂), 3.71 (br s, 2H, 6-H₂), 3.61 (dd, J = 9.2, 9.2 Hz, 1H, 4-H), 3.52 (dd, J = 8.6, 8.6 Hz, 1H, 3-H), 3.42 (ddd, J = 9.6, 2.9, 2.9 Hz, 1H, 5-H), 3.39 (dd, J = 9.1, 9.1 Hz, 1H, 2-H), 3.28 (ddd, J = 8.2, 8.2, 2.2 Hz, 1H, 1-H), 2.14–1.98 (m, 2H, 1’-H_b, 2’-H_b), 1.87 (m, 1H, 2’-H_a), 1.71 ppm (m, 1H, 1’-H_a), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 163.7 (2 × C, CO), 138.7 (C, Ar), 138.2 (2 × C, Ar), 134.8 (2 × CH, Ar), 129.4 (2 × C, Ar), 129.0 (2 × CH, Ar), 128.8 (2 × CH, Ar), 128.7 (2 × CH, Ar), 128.31 (2 × CH, Ar), 128.25 (2 × CH, Ar), 128.2 (CH, Ar), 128.14 (2 × CH, Ar), 128.11 (CH, Ar), 127.9 (CH, Ar), 123.9 (2 × CH, Ar), 87.0 (CH, C-3), 79.1 (CH, C-1 or C-5), 78.9 (CH, C-1 or C-5), 78.6 (CH₂, C-3’), 78.4 (CH, C-4), 75.2 (CH₂, OBn), 74.8 (CH₂, OBn), 73.9 (CH, C-2), 73.5 (CH₂, OBn), 69.1 (CH₂, C-6), 27.7 (CH₂, C-1’), 24.0 ppm (CH₂, C-2’). IR (CHCl₃): ν = 3565, 2926, 2860, 1791, 1737, 1370, 1097 cm^–1. MS (ESI) m/z (%) = 660 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₈H₃₉NNaO₈ 660.2573; found 660.2558.

3-C-(3,4,6-Tri-O-benzyl-α-d-mannopyranosyl)1-propoxyphthalimide (70)

Following the general procedure starting from alcohol 69 (178.8 mg, 0.36 mmol) and purification by column chromatography (hexanes–EtOAc, 1:1), product 70 (206 mg, 0.32 mmol, 90%) was obtained as a colorless oil: [α]_D = +13.5 (c = 1.50, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.83–7.81 (m, 2H, Ar), 7.74–7.73 (m, 2H, Ar), 7.34–7.20 (m, 15H, Ar), 4.73 (d, J = 11.4 Hz, 1H, OBn), 4.65 (d, J = 12.3 Hz, 1H, OBn), 4.63 (d, J = 11.7 Hz, 1H, OBn), 4.56 (d, J = 12.0 Hz, 1H, OBn), 4.53 (d, J = 11.4 Hz, 1H, OBn), 4.50 (d, J = 12.0 Hz, 1H, OBn), 4.27–4.19 (m, 2H, 3’-H₂), 3.97 (m, 1H, 1-H), 3.89 (dd, J = 3.6, 2.9 Hz, 1H, 2-H), 3.83 (dd, J = 7.2, 3.1 Hz, 1H, 3-H), 3.81 (dd, J = 6.6, 6.6 Hz, 1H, 4-H), 3.77 (m, 1H, 5-H), 3.73 (dd, J = 10.4, 5.1 Hz, 1H, 6-H_b), 3.68 (dd, J = 10.4, 3.5 Hz, 1H, 6-H_a), 1.94 (m, 1H, 2’-H_b), 1.88–1.78 ppm (m, 3H, 1’-H₂, 2’-H_a), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 163.6 (2 × C, CO), 138.3 (C, Ar), 138.2 (C, Ar), 137.7 (C, Ar), 134.4 (2 × CH, Ar), 129.0 (2 × C, Ar), 128.6 (2 × CH, Ar), 128.4 (2 × CH, Ar), 128.3 (2 × CH, Ar), 128.0 (CH, Ar), 127.9 (4 × CH, Ar), 127.73 (2 × CH, Ar), 127.68 (CH, Ar), 127.5 (CH, Ar), 123.5 (2 × CH, Ar), 79.4 (CH, C-3 or C-4), 78.0 (CH₂, C-3’), 74.8 (CH, C-1), 74.3 (CH, C-5), 74.1 (CH₂, OBn), 73.4 (CH₂, OBn), 72.8 (CH, C-3 or C-4), 72.3 (CH₂, OBn), 69.3 (CH, C-2), 69.1 (CH₂, C-6), 25.5 (CH₂, C-1’ or C-2’), 24.6 ppm (CH₂, C-1’ or C-2’). IR (CHCl₃): ν = 3559, 2930, 1789, 1731, 1082 cm^–1. MS (ESI) m/z (%) = 660 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₈H₃₉NNaO₈ 660.2573; found 660.2578.

3-C-(3,4,6-Tri-O-benzyl-β-d-mannopyranosyl)1-propoxyphthalimide (73)

Following the general procedure starting from alcohol 72 (72.6 mg, 0.15 mmol) and purification by column chromatography (hexanes–Et₂O, 1:1), product 73 (80 mg, 0.13 mmol, 84%) was obtained as a colorless oil: [α]_D = +5.3 (c = 0.34, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.83–7.80 (m, 2H, Ar), 7.75–7.72 (m, 2H, Ar), 7.38–7.18 (m, 15H, Ar), 4.85 (d, J = 10.7 Hz, 1H, OBn), 4.75 (d, J = 11.7 Hz, 1H, OBn), 4.67 (d, J = 11.7 Hz, 1H, OBn), 4.60 (d, J = 12.3 Hz, 1H, OBn), 4.53 (d, J = 10.4 Hz, 1H, OBn), 4.53 (d, J = 12.3 Hz, 1H, OBn), 4.29–4.20 (m, 2H, 3’-H₂), 3.98 (dd, J = 2.9, 0.6 Hz, 1H, 2-H), 3.78 (dd, J = 9.4, 9.2 Hz, 1H, 4-H), 3.72 (dd, J = 11.3, 1.9 Hz, 1H, 6-H_b), 3.68 (dd, J = 11.3, 5.0 Hz, 1H, 6-H_a), 3.63 (dd, J = 9.2, 2.9 Hz, 1H, 3-H), 3.47 (ddd, J = 7.9, 4.1, 0.6 Hz, 1H, 1-H), 3.41 (ddd, J = 9.4, 5.0, 1.9 Hz, 1H, 5-H), 2.31 (br s, 1H, OH), 2.04–1.94 (m, 2H, 1’-H_b, 2’-H_b), 1.92–1.84 ppm (m, 2H, 1’-H_a, 2’-H_a). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 163.6 (2 × C, CO), 138.4 (2 × C, Ar), 137.9 (C, Ar), 134.4 (2 × CH, Ar), 129.0 (2 × C, Ar), 128.5 (2 × CH, Ar), 128.30 (2 × CH, Ar), 128.26 (2 × CH, Ar), 127.93 (2 × CH, Ar), 127.88 (3 × CH, Ar), 127.8 (2 × CH, Ar), 127.6 (CH, Ar), 127.5 (CH, Ar), 123.4 (2 × CH, Ar), 83.6 (CH, C-3), 79.2 (CH, C-1), 78.3 (CH₂, C-3’), 77.3 (CH, C-5), 75.1 (CH₂, OBn), 74.8 (CH, C-4), 73.4 (CH₂, OBn), 71.6 (CH₂, OBn), 69.5 (CH₂, C-6), 68.4 (CH, C-2), 27.1 (CH₂, C-2’), 24.7 ppm (CH₂, C-1’). IR (CHCl₃): ν = 3569, 2927, 2862, 1792, 1737, 1118 cm^–1. MS (ESI) m/z (%) = 660 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₈H₃₉NNaO₈ 660.2573; found 660.2576. Anal. calcd for C₃₈H₃₉NO₈: C, 71.57; H, 6.16; N, 2.20. Found: C, 71.62; H, 6.30; N, 1.95.

3-C-(3,4-Di-O-benzyl-α-l-fucopyranosyl)1-propoxyphthalimide (77)

Following the general procedure starting from alcohol 76 (413 mg, 1.07 mmol) and purification by column chromatography (hexanes–EtOAc, 7:3), product 77 (536.9 mg, 1.01 mmol, 94%) was obtained as a colorless oil: [α]_D = −14.4 (c = 0.80, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.83–7.81 (m, 2H, Ar), 7.74–7.73 (m, 2H, Ar), 7.37–7.24 (m, 10H, Ar), 4.79 (d, J = 11.7 Hz, 1H, OBn), 4.76 (d, J = 11.9 Hz, 1H, OBn), 4.62 (d, J = 12.0 Hz, 1H, OBn), 4.61 (d, J = 12.0 Hz, 1H, OBn), 4.28–4.21 (m, 2H, 3’-H₂), 4.14–4.07 (m, 2H, 1-H, 2-H), 3.94 (m, 1H, 5-H), 3.79 (dd, J = 2.8, 2.8 Hz, 1H, 4-H), 3.76 (dd, J = 7.3, 2.9 Hz, 1H, 3-H), 2.52 (br s, 1H, OH), 2.04–1.77 (m, 4H, 1’-H₂, 2’-H₂), 1.30 ppm (d, J = 6.7 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.6 (2 × C, CO), 138.5 (C, Ar), 138.3 (C, Ar), 128.9 (2 × C, Ar), 128.5 (2 × CH, Ar), 128.4 (3 × CH, Ar), 128.2 (2 × CH, Ar), 127.7 (2 × CH, Ar), 127.6 (CH, Ar), 127.5 (2 × CH, Ar), 123.4 (2 × CH, Ar), 79.2 (CH, C-3), 78.3 (CH₂, C-3’), 75.3 (CH, C-4), 73.2 (CH₂, OBn), 72.5 (CH₂, OBn), 71.9 (CH, C-2), 68.7 (CH, C-1), 68.6 (CH, C-5), 24.9 (CH₂, C-1’ or C-2’), 22.8 (CH₂, C-1’ or C-2’), 15.7 ppm (CH₃, C-6). IR (CHCl₃): ν = 3675, 3574, 3015, 1790, 1733, 1120 cm^–1. MS (ESI) m/z (%) = 554 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₁H₃₃NNaO₇ 554.2155; found 554.2147.

3-C-(3,5-Di-O-1,1,3,3-tetraisopropyldisiloxanyl-α-d-ribofuranosyl)1-propoxyphthalimide (88)

Following the general procedure starting from alcohol 87 (350 mg, 0.81 mmol) and purification by column chromatography (hexanes–EtOAc, 8:2), product 88 (457.9 mg, 0.79 mmol, 98%) was obtained as a colorless oil: [α]_D = −13.0 (c = 0.73, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.83–7.72 (m, 4H, Ar), 4.36 (dd, J = 7.2, 4.8 Hz, 1H, 3-H), 4.25–4.20 (m, 2H, 3’-H₂), 4.11 (dd, J = 4.8, 3.4 Hz, 1H, 2-H), 4.04 (m, 1H, 1-H), 3.95 (dd, J = 11.4, 3.2 Hz, 1H, 5-H_b), 3.89 (ddd, J = 6.1, 6.1, 3.4 Hz, 1H, 4-H), 3.83 (dd, J = 11.6, 6.1 Hz, 1H, 5-H_a), 1.96–1.80 (m, 4H, 1’-H₂, 2’-H₂), 1.09–0.97 ppm (m, 28H, ⁱPr), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.6 (2 × C, CO), 134.4 (2 × CH, Ar), 129.0 (2 × C, Ar), 123.4 (2 × CH, Ar), 80.2 (CH, C-1 or C-4), 80.2 (CH, C-1 or C-4), 78.3 (CH₂, C-3’), 74.6 (CH, C-3), 72.5 (CH, C-2), 63.1 (CH₂, C-5), 25.3 (CH₂, C-1’ or C-2’), 24.7 (CH₂, C-1’ or C-2’), 17.43 (CH₃, ⁱPr), 17.31 (3 × CH₃, ⁱPr), 17.19 (CH₃, ⁱPr), 17.02 (2 × CH₃, ⁱPr), 16.94 (CH₃, ⁱPr), 13.4 (CH, ⁱPr), 13.2 (CH, ⁱPr), 12.8 (CH, ⁱPr), 12.6 ppm (CH, ⁱPr). IR (CHCl₃): ν = 3546, 2948, 1791, 1733, 1467, 1039 cm^–1. MS (ESI) m/z (%) = 602 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₈H₄₅NNaO₈Si₂ 602.2581; found 602.2585.

General Procedure to Give Acetyl Derivatives 1, 3, 5, 7, and 9

The phthalimide (1 mmol) was dissolved in dry pyridine (3.83 mL), and acetyl anhydride (1.1 mL) and DMAP (12.6 mg, 0.1 mmol) were added at 0 °C under a N₂ atmosphere. The mixture was stirred at room temperature for 1 h. Then, the reaction was evaporated on the high vacuum rotovap, and the crude was quenched with HCl 10% and extracted with CH₂Cl₂. The organic extracts were washed with a saturated aqueous NaHCO₃ solution, dried over Na₂SO₄, and concentrated under reduced pressure. Column chromatography of the residue (hexanes–EtOAc) gave the corresponding acetyl compound.

3-C-(2-O-Acetyl-3,4,6-tri-O-benzyl-α-d-glucopyranosyl)1-propoxyphthalimide (1)

Following the general procedure starting from phthalimide 64 (39.2 mg, 0.06 mmol) and purification by column chromatography (hexanes–EtOAc, 85:15), product 1 (30 mg, 0.04 mmol, 72%) was obtained as a crystalline solid: mp 99.7–100.5 °C (n-hexane–EtOAc); [α]_D = +46.8 (c = 0.31, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.83–7.80 (m, 2H, Ar), 7.74–7.71 (m, 2H, Ar), 7.34–7.15 (m, 15H, Ar), 5.08 (dd, J = 9.0, 5.5 Hz, 1H, 2-H), 4.78 (d, J = 11.7 Hz, 1H, OBn), 4.75 (d, J = 11.1 Hz, 1H, OBn), 4.74 (d, J = 11.4 Hz, 1H, OBn), 4.60 (d, J = 12.3 Hz, 1H, OBn), 4.50 (d, J = 11.1 Hz, 1H, OBn), 4.48 (d, J = 12.0 Hz, 1H, OBn), 4.24 (dd, J = 6.0, 6.0 Hz, 2H, 3’-H₂), 4.17 (ddd, J = 11.0, 5.5, 3.1 Hz, 1H, 1-H), 3.87 (dd, J = 9.0, 7.8 Hz, 1H, 3-H), 3.73–3.65 (m, 4H, 4-H, 5-H, 6-H₂), 2.04 (s, 3H, OAc), 1.99–1.90 (m, 2H, 1’-H_b, 2’-H_b), 1.84–1.73 ppm (m, 2H, 1’-H_a, 2’-H_a). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 170.1 (C, OAc), 163.5 (2 × C, CO), 138.5 (C, Ar), 138.1 (2 × C, Ar), 134.4 (2 × CH, Ar), 129.0 (2 × C, Ar), 128.4 (2 × CH, Ar), 128.34 (2 × CH, Ar), 128.31 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.73 (2 × CH, Ar), 127.69 (CH, Ar), 127.61 (CH, Ar), 127.59 (2 × CH, Ar), 127.5 (CH, Ar), 123.4 (2 × CH, Ar), 80.1 (CH, C-3), 77.9 (CH₂, C-3’), 77.6 (CH, C-4 or C-5), 74.8 (CH₂, OBn), 74.6 (CH₂, OBn), 73.5 (CH₂, OBn), 73.0 (CH, C-2), 72.1 (CH, C-1), 71.9 (CH, C-4 or C-5), 69.0 (CH₂, C-6), 24.3 (CH₂, C-1’ or C-2’), 22.1 (CH₂, C-1’ or C-2’), 20.9 ppm (CH₃, OAc). IR (CHCl₃): ν = 3013, 2870, 1790, 1734, 1236 cm^–1. MS (ESI) m/z (%) = 702 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₄₁NNaO₉ 702.2679; found 702.2680. Anal. calcd for C₄₀H₄₁NO₉: C, 70.68; H, 6.08; N, 2.06. Found C, 70.55; H, 6.07; N, 2.24.

3-C-(2-O-Acetyl-3,4,6-tri-O-benzyl-β-d-glucopyranosyl)1-propoxyphthalimide (3)

Following the general procedure starting from phthalimide 67 (790 mg, 1.26 mmol) and purification by column chromatography (hexanes–EtOAc, 7:3 to 1:1), product 3 (600 mg, 0.88 mmol, 71%) was obtained as a colorless oil: [α]_D = +17.7 (c = 0.62, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.82–7.78 (m, 2H, Ar), 7.74–7.70 (m, 2H, Ar), 7.33–7.16 (m, 15H, Ar), 4.90 (dd, J = 9.5, 9.5 Hz, 1H, 2-H), 4.82 (d, J = 11.6 Hz, 1H, OBn), 4.78 (d, J = 10.8 Hz, 1H, OBn), 4.67 (d, J = 11.4 Hz, 1H, OBn), 4.60 (d, J = 12.3 Hz, 1H, OBn), 4.55 (d, J = 12.6 Hz, 1H, OBn), 4.51 (d, J = 12.3 Hz, 1H, OBn), 4.25 (m, 1H, 3’-H_b), 4.17 (m, 1H, 3’-H_a), 3.74–3.64 (m, 4H, 3-H, 4-H, 6-H₂), 3.44 (ddd, J = 8.0, 4.0, 2.2 Hz, 1H, 5-H), 3.38 (ddd, J = 9.2, 9.2, 1.9 Hz, 1H, 1-H), 2.01 (m, 1H, 2’-H_b), 1.99 (s, 3H, OAc), 1.89–1.81 (m, 2H, 1’-H_b, 2’-H_a), 1.60 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 170.0 (C, OAc), 163.5 (2 × C, CO), 138.4 (C, Ar), 138.2 (C, Ar), 138.1 (C, Ar), 134.3 (2 × CH, Ar), 129.0 (2 × C, Ar), 128.4 (2 × CH, Ar), 128.33 (2 × CH, Ar), 128.28 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.7 (CH, Ar), 127.64 (4 × CH, Ar), 127.56 (CH, Ar), 127.5 (CH, Ar), 123.4 (2 × CH, Ar), 84.7 (CH, C-2), 79.1 (CH, C-3), 78.4 (CH, C-4), 78.1 (CH₂, C-3’), 77.4 (CH, C-5), 75.1 (CH₂, OBn), 74.9 (CH₂, OBn), 73.8 (CH, C-1), 73.4 (CH₂, OBn), 69.0 (CH₂, C-6), 27.5 (CH₂, C-1’), 24.0 (CH₂, C-2’), 20.9 ppm (CH₃, OAc). IR (CHCl₃): ν = 3032, 2926, 2863, 1792, 1737, 1455, 1371, 1231, 1103 cm^–1. MS (ESI) m/z (%) = 702 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₄₁NNaO₉ 702.2679; found 702.2689. Anal. calcd for C₄₀H₄₁NO₉: C, 70.68; H, 6.08; N, 2.06. Found: C, 70.69; H, 6.20; N, 2.33.

3-C-(2-O-Acetyl-3,4,6-tri-O-benzyl-α-d-mannopyranosyl)1-propoxyphthalimide (5)

Following the general procedure starting from phthalimide 70 (99.2 mg, 0.16 mmol) and purification by column chromatography (hexanes–EtOAc, 6:4), product 5 (90.7 mg, 0.13 mmol, 86%) was obtained as a colorless oil: [α]_D = +5.4 (c = 0.43, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.83–7.81 (m, 2H, Ar), 7.74–7.72 (m, 2H, Ar), 7.33–7.17 (m, 15H, Ar), 5.30 (dd, J = 3.4, 2.6 Hz, 1H, 2-H), 4.82 (d, J = 11.0 Hz, 1H, OBn), 4.69 (d, J = 11.4 Hz, 1H, OBn), 4.63 (d, J = 12.0 Hz, 1H, OBn), 4.54 (d, J = 11.4 Hz, 1H, OBn), 4.50 (d, J = 12.3 Hz, 1H, OBn), 4.49 (d, J = 11.1 Hz, 1H, OBn), 4.27–4.19 (m, 2H, 3’-H₂), 4.03 (ddd, J = 10.9, 4.1, 2.6 Hz, 1H, 1-H), 3.93 (dd, J = 8.7, 3.4 Hz, 1H, 3-H), 3.85 (dd, J = 8.7, 8.4 Hz, 1H, 4-H), 3.78–3.69 (m, 3H, 5-H, 6-H₂), 2.14 (s, 3H, OAc), 2.01–1.91 (m, 2H, 1’-H₂), 1.87–1.77 ppm (m, 2H, 2’-H₂). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 170.6 (C, OAc), 163.6 (2 × C, CO), 138.4 (2 × C, Ar), 137.9 (C, Ar), 134.4 (2 × CH, Ar), 129.0 (2 × C, Ar), 128.4 (2 × CH, Ar), 128.31 (2 × CH, Ar), 128.29 (2 × CH, Ar), 128.1 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.8 (CH, Ar), 127.7 (2 × CH, Ar), 127.6 (CH, Ar), 127.5 (CH, Ar), 123.5 (2 × CH, Ar), 77.9 (CH, C-3), 77.8 (CH₂, C-3’), 75.0 (CH, C-4), 74.8 (CH, C-5), 74.7 (CH₂, OBn), 73.5 (CH₂, OBn), 72.8 (CH, C-1), 72.0 (CH₂, OBn), 70.7 (CH, C-2), 69.4 (CH₂, C-6), 25.0 (CH₂, C-1’ or C-2’), 24.8 (CH₂, C-1’ or C-2’), 21.2 ppm (CH₃, OAc). IR (CHCl₃): ν = 3034, 2929, 1790, 1734, 1189 cm^–1. MS (ESI) m/z (%) = 702 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₄₁NNaO₉ 702.2679; found 702.2687. Anal. calcd for C₄₀H₄₁NO₉: C, 70.68; H, 6.08; N, 2.06. Found: C, 70.74; H, 6.12; N, 2.04.

3-C-(2-O-Acetyl-3,4,6-tri-O-benzyl-β-d-mannopyranosyl)1-propoxyphthalimide (7)

Following the general procedure starting from phthalimide 73 (77 mg, 0.11 mmol) and purification by column chromatography (hexanes–EtOAc, 8:2), product 7 (60 mg, 0.09 mmol, 80%) was obtained as a colorless oil: [α]_D = −16.7 (c = 0.63, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated coupling constants using DAISY) δ_H 7.82–7.79 (m, 2H, Ar), 7.74–7.72 (m, 2H, Ar), 7.34–7.16 (m, 15H, Ar), 5.52 (dd, J = 3.3, 1.0 Hz, 1H, 2-H), 4.86 (d, J = 10.8 Hz, 1H, OBn), 4.77 (d, J = 11.1 Hz, 1H, OBn), 4.64 (d, J = 12.3 Hz, 1H, OBn), 4.52 (d, J = 11.7 Hz, 1H, OBn), 4.50 (d, J = 10.4 Hz, 1H, OBn), 4.50 (d, J = 10.4 Hz, 1H, OBn), 4.25–4.18 (m, 2H, 3’-H₂), 3.77 (dd, J = 9.8, 9.3 Hz, 1H, 4-H), 3.74 (m, 2H, 6-H₂), 3.70 (dd, J = 9.3, 3.3 Hz, 1H, 3-H), 3.63 (ddd, J = 8.3, 4.7, 1.0 Hz, 1H, 1-H), 3.47 (ddd, J = 9.8, 5.3, 2.1 Hz, 1H, 5-H), 2.19 (s, 3H, OAc), 1.97 (m, 1H, 2’-H_b), 1.90–1.83 (m, 2H, 1’-H_b, 2’-H_a), 1.72 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.8 (C, OAc), 163.6 (2 × C, CO), 138.4 (C, Ar), 138.3 (C, Ar), 137.9 (C, Ar), 134.4 (2 × CH, Ar), 128.9 (2 × C, Ar), 128.34 (2 × CH, Ar), 128.26 (4 × CH, Ar), 128.1 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.8 (2 × CH, Ar), 127.7 (CH, Ar), 127.6 (CH, Ar), 127.5 (CH, Ar), 123.4 (2 × CH, Ar), 81.9 (CH, C-3), 79.4 (CH, C-5), 78.0 (CH₂, C-3’), 76.2 (CH, C-1), 75.1 (CH₂, OBn), 74.6 (CH, C-4), 73.4 (CH₂, OBn), 71.5 (CH₂, OBn), 69.4 (CH₂, C-6), 69.2 (CH, C-2), 27.2 (CH₂, C-1’ or C-2’), 24.4 (CH₂, C-1’ or C-2’), 21.0 ppm (CH₃, OAc). IR (CHCl₃): ν = 3033, 2951, 2866, 1792, 1737, 1237, 1120 cm^–1. MS (ESI) m/z (%) = 702 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₄₁NNaO₉ 702.2679; found 702.2675. Anal. calcd for C₄₀H₄₁NO₉: C, 70.68; H, 6.08; N, 2.06. Found: C, 70.77; H, 6.05; N, 2.10.

3-C-(2-O-Acetyl-3,4-di-O-benzyl-α-l-fucopyranosyl)1-propoxyphthalimide (9)

Following the general procedure starting from phthalimide 77 (247.4 mg, 0.46 mmol) and purification by column chromatography (hexanes–EtOAc, 9:1 to7:3), product 9 (153.6 mg, 0.27 mmol, 58%) was obtained as a colorless oil: [α]_D = −21.6 (c = 0.74, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated coupling constants using DAISY) δ_H 7.84–7.81 (m, 2H, Ar), 7.74–7.73 (m, 2H, Ar), 7.39–7.25 (m, 10H, Ar), 5.16 (dd, J = 5.9, 3.0 Hz, 1H, 2-H), 4.75 (d, J = 12.0 Hz, 1H, OBn), 4.70 (d, J = 12.0 Hz, 1H, OBn), 4.66 (d, J = 12.0 Hz, 1H, OBn), 4.55 (d, J = 12.0 Hz, 1H, OBn), 4.22 (dd, J = 5.0, 5.0 Hz, 2H, 3’-H₂), 4.15 (ddd, J = 9.4, 4.1, 3.0 Hz, 1H, 1-H), 4.06 (dddd, J = 6.7, 6.7, 6.7, 4.5 Hz, 1H, 5-H), 3.82 (dd, J = 5.9, 3.2 Hz, 1H, 3-H), 3.74 (dd, J = 4.5, 3.2 Hz, 1H, 4-H), 2.08 (s, 3H, OAc), 1.91 (m, 1H, 2’-H_b), 1.81–1.74 (m, 2H, 1’-H_b, 2’-H_a), 1.66 (m, 1H, 1’-H_a), 1.36 ppm (d, J = 6.7 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.3 (C, OAc). 163.6 (2 × C, CO), 138.4 (C, Ar), 138.3 (C, Ar), 134.4 (2 × CH, Ar), 128.9 (2 × C, Ar), 128.28 (2 × CH, Ar), 128.26 (2 × CH, Ar), 127.7 (2 × CH, Ar), 127.6 (CH, Ar), 127.51 (CH, Ar), 127.46 (2 × CH, Ar), 123.4 (2 × CH, Ar), 78.1 (CH₂, C-3’), 75.6 (CH, C-3), 74.6 (CH, C-4), 72.9 (CH₂, OBn), 72.2 (CH₂, OBn), 71.4 (CH, C-2), 69.5 (CH, C-5), 67.6 (CH, C-1), 24.9 (CH₂, C-1’), 24.7 (CH₂, C-2’), 21.0 (CH₃, OAc), 14.6 ppm (CH₃, C-6). IR (CHCl₃): ν = 3029, 1791, 1734, 1214 cm^–1. MS (ESI) m/z (%) = 596 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₃H₃₅NNaO₈ 596.2260; found 596.2264. Anal. calcd for C₃₃H₃₅NO₈: C, 69.10; H, 6.15; N, 2.44. Found: C, 69.25; H, 6.41; N, 2.58.

General Procedure to Give Diphenoxyphosphoryl Derivatives 2, 4, 6, 8, 10, and 15

The phthalimide (1 mmol) was dissolved in dry CH₂Cl₂ (7.5 mL) under a N₂ atmosphere. ClPO(OPh)₂ (1 mL, 4.7 mmol) and DMAP (580 mg, 4.75 mmol) were added at 0 °C, and after 5 min, the mixture was stirred at room temperature for 2 h. The reaction was quenched with a saturated aqueous NH₄Cl solution and extracted with CH₂Cl₂. The organic extracts were dried over Na₂SO₄ and concentrated under reduced pressure. Column chromatography of the residue (hexanes–EtOAc) gave the phosphatyl precursor.

3-C-(3,4,6-Tri-O-benzyl-2-O-diphenoxyphosphoryl-α-d-glucopyranosyl)1-propoxyphthalimide (2)

Following the general procedure starting from phthalimide 64 (129.8 mg, 0.20 mmol) and purification by column chromatography (hexanes–EtOAc, 75:25), product 2 (132.6 mg, 0.15 mmol, 76%) was obtained as a colorless oil: [α]_D = +40.5 (c = 0.44, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.83–7.81 (m, 2H, Ar), 7.74–7.72 (m, 2H, Ar), 7.30–7.10 (m, 25H, Ar), 4.83 (d, J = 11.0 Hz, 1H, OBn), 4.80 (ddd, J = 10.5, 5.5 Hz, ³J_PH = 8.6 Hz, 1H, 2-H), 4.75 (d, J = 11.0 Hz, 1H, OBn), 4.74 (d, J = 11.1 Hz, 1H, OBn), 4.60 (d, J = 12.0 Hz, 1H, OBn), 4.46 (d, J = 11.0 Hz, 1H, OBn), 4.45 (d, J = 12.0 Hz, 1H, OBn), 4.20–4.15 (m, 2H, 3’-H₂), 4.12 (ddd, J = 9.4, 7.2, 5.5 Hz, 1H, 1-H), 3.91 (ddd, J = 10.5, 5.7 Hz, ⁴J_PH = 2.9 Hz, 1H, 3-H), 3.71–3.64 (m, 4H, 4-H, 5-H, 6-H₂), 1.97 (m, 1H, 1’-H_b or 2’-H_b), 1.90 (m, 1H, 1’-H_b or 2’-H_b), 1.72 (m, 1H, 1’-H_a or 2’-H_a), 1.63 ppm (m, 1H, 1’-H_a or 2’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.5 (2 × C, CO). 150.5 (d, ²J_PC = 7.0 Hz, C, Ar), 150.4 (d, ²J_PC = 6.4 Hz, C, Ar), 138.1 (C, Ar), 138.0 (C, Ar), 137.9 (C, Ar), 134.4 (2 × CH, Ar), 129.8 (2 × CH, Ar), 129.7 (2 × CH, Ar), 128.9 (2 × C, Ar), 128.3 (4 × CH, Ar), 128.2 (2 × CH, Ar), 127.8 (6 × CH, Ar), 127.7 (CH, Ar), 127.6 (CH, Ar), 127.5 (CH, Ar), 125.4 (CH, Ar), 125.2 (CH, Ar), 123.4 (2 × CH, Ar), 120.22 (CH, Ar), 120.18 (CH, Ar), 119.99 (CH, Ar), 119.95 (CH, Ar), 80.5 (d, ³J_PC = 6.3 Hz, CH, C-3), 78.4 (d, ²J_PC = 7.4 Hz, CH, C-2), 77.9 (CH₂, C-3’), 77.8 (CH, C-1), 75.1 (CH₂, OBn), 74.8 (CH₂, OBn), 73.7 (CH, C-4 or C-5), 73.5 (CH₂, OBn), 71.4 (CH, C-4 or C-5), 68.9 (CH₂, C-6), 24.3 (CH₂, C-1’ or C-2’), 21.1 ppm (CH₂, C-1’ or C-2’). IR (CHCl₃): ν = 3021, 2946, 1790, 1734, 1213 cm^–1. MS (ESI) m/z (%) = 892 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₅₀H₄₈NNaO₁₁P 892.2863; found 892.2856. Anal. calcd for C₅₀H₄₈NO₁₁P: C, 69.04; H; 5.56; N, 1.61. Found: C, 69.39; H, 5.74; N, 1.71.

3-C-(3,4,6-Tri-O-benzyl-2-O-diphenoxyphosphoryl-β-d-glucopyranosyl)1-propoxyphthalimide (4)

Following the general procedure starting from phthalimide 67 (327 mg, 0.51 mmol) and purification by column chromatography (hexanes–EtOAc, 7:3), product 4 (224 mg, 0.26 mmol, 51%) was obtained as a colorless oil: [α]_D = +9.9 (c = 0.83, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated coupling constants using DAISY) δ_H 7.83–7.80 (m, 2H, Ar), 7.74–7.70 (m, 2H, Ar), 7.30–7.06 (m, 25H, Ar), 4.88 (d, J = 10.8 Hz, 1H, OBn), 4.83 (d, J = 10.8 Hz, 1H, OBn), 4.74 (d, J = 11.1 Hz, 1H, OBn), 4.58 (d, J = 12.3 Hz, 1H, OBn), 4.54 (d, J = 10.7 Hz, 1H, OBn), 4.49 (d, J = 12.3 Hz, 1H, OBn), 4.43 (ddd, J = 9.5, 8.9 Hz, ³J_PH = 8.2 Hz, 1H, 2-H), 4.13 (ddd, J = 8.8, 7.6, 6.3 Hz, 1H, 3’-H_b), 4.04 (ddd, J = 8.8, 7.6, 6.6 Hz, 1H, 3’-H_a), 3.78 (dd, J = 9.2, 9.2 Hz, 1H, 3-H), 3.72–3.66 (m, 2H, 6-H₂), 3.70 (dd, J = 9.5, 9.3 Hz, 1H, 4-H), 3.48 (dddd, J = 9.5, 8.2, 8.1, 2.5 Hz, 1H, 1-H), 3.45 (ddd, J = 9.5, 3.8, 1.8 Hz, 1H, 5-H), 2.00 (m, 1H, 2’-H_b), 1.89 (m, 1H, 2’-H_a), 1.83 (m, 1H, 1’-H_b), 1.57 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 163.4 (2 × C, CO), 150.6 (d, ²J_PC = 7.1 Hz, C, Ar), 150.5 (d, ²J_PC = 7.1 Hz, C, Ar), 138.3 (C, Ar), 138.1 (C, Ar), 138.0 (C, Ar), 134.3 (2 × CH, Ar), 129.6 (2 × CH, Ar), 129.5 (2 × CH, Ar), 129.0 (2 × C, Ar), 128.28 (2 × CH, Ar), 128.26 (2 × CH, Ar), 128.0 (2 × CH, Ar), 127.7 (2 × CH, Ar), 127.6 (3 × CH, Ar), 127.5 (3 × CH, Ar), 127.2 (CH, Ar), 125.3 (CH, Ar), 125.0 (CH, Ar), 123.3 (2 × CH, Ar), 120.4 (CH, Ar), 120.3 (CH, Ar), 120.1 (CH, Ar), 120.0 (CH, Ar), 84.7 (d, ³J_PC = 2.1 Hz, CH, C-3), 80.6 (d, ²J_PC = 7.7 Hz, CH, C-2), 79.0 (CH, C-4), 78.5 (CH, C-5), 78.0 (CH₂, C-3’), 77.8 (d, ³J_PC = 4.9 Hz, CH, C-1), 75.0 (CH₂, OBn), 74.8 (CH₂, OBn), 73.4 (CH₂, OBn), 68.8 (CH₂, C-6), 27.2 (CH₂, C-1’), 23.9 ppm (CH₂, C-2’). IR (CHCl₃): ν = 3013, 2870, 1776, 1736, 1240, 1090 cm^–1. MS (ESI) m/z (%) = 892 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₅₀H₄₈NNaO₁₁P 892.2863; found 892.2879. Anal. calcd for C₅₀H₄₈NO₁₁P: C, 69.04; H, 5.56; N, 1.61. Found: C, 69.15; H, 5.64; N, 1.99.

3-C-(3,4,6-Tri-O-benzyl-2-O-diphenoxyphosphoryl-α-d-mannopyranosyl)1-propoxyphthalimide (6)

Following the general procedure starting from phthalimide 70 (109.2 mg, 0.17 mmol) and purification by column chromatography (hexanes–EtOAc, 65:35), product 6 (110.6 mg, 0.13 mmol, 74%) was obtained as a colorless oil: [α]_D = −10.7 (c = 0.54, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.80–7.79 (m, 2H, Ar), 7.74–7.70 (m, 2H, Ar), 7.34–7.06 (m, 25H, Ar), 4.96 (ddd, J = 2.9, 2.9 Hz, ³J_PH = 8.2 Hz, 1H, 2-H), 4.81 (d, J = 11.1 Hz, 1H, OBn), 4.67 (d, J = 11.0 Hz, 1H, OBn), 4.57 (d, J = 12.0 Hz, 1H, OBn), 4.53 (d, J = 11.4 Hz, 1H, OBn), 4.49 (d, J = 12.3 Hz, 1H, OBn), 4.40 (d, J = 11.0 Hz, 1H, OBn), 4.21–4.16 (m, 2H, 3’-H₂), 4.07 (ddd, J = 9.8, 3.8, 3.8 Hz, 1H, 1-H), 3.92 (m, 1H, 3-H), 3.74–3.66 (m, 4H, 4-H, 5-H, 6-H₂), 1.94–1.85 (m, 2H, 1’-H_b, 2’-H_b), 1.81–1.70 ppm (m, 2H, 1’-H_a, 2’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.5 (2 × C, CO), 150.7 (d, ²J_PC = 7.4 Hz, C, Ar), 150.5 (d, ²J_PC = 7.4 Hz, C, Ar), 138.3 (C, Ar), 138.1 (C, Ar), 137.7 (C, Ar), 134.3 (2 × CH, Ar), 129.7 (2 × CH, Ar), 129.5 (2 × CH, Ar), 128.9 (2 × C, Ar), 128.3 (2 × CH, Ar), 128.24 (4 × CH, Ar), 128.19 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.64 (2 × CH, Ar), 127.59 (2 × CH, Ar), 127.4 (CH, Ar), 125.2 (CH, Ar), 125.0 (CH, Ar), 123.4 (2 × CH, Ar), 120.3 (CH, Ar), 120.24 (CH, Ar), 120.18 (CH, Ar), 120.1 (CH, Ar), 77.8 (d, ³J_PC = 3.2 Hz, CH, C-3), 77.7 (CH₂, C-3’), 77.5 (d, ²J_PC = 6.4 Hz, CH, C-2), 74.9 (br s, CH, C-1), 74.5 (CH₂, OBn), 74.3 (CH, C-4 or C-5), 73.3 (CH₂, OBn), 73.0 (CH, C-4 or C-5), 72.1 (CH₂, OBn), 69.1 (CH₂, C-6), 24.8 (CH₂, C-1’ or C-2’), 24.6 ppm (CH₂, C-1’ or C-2’). IR (CHCl₃): ν = 2929, 2858, 1793, 1737, 1491, 1191 cm^–1. MS (ESI) m/z (%) = 892 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₅₀H₄₈NNaO₁₁P 892.2863; found 892.2864. Anal. calcd for C₅₀H₄₈NO₁₁P: C, 69.04; H, 5.56; N, 1.61. Found: C, 68.91; H, 5.95; N, 1.91.

3-C-(3,4,6-Tri-O-benzyl-2-O-diphenoxyphosphoryl-β-d-mannopyranosyl)1-propoxyphthalimide (8)

Following the general procedure starting from phthalimide 73 (220 mg, 0.34 mmol) and purification by column chromatography (hexanes–EtOAc, 7:3), product 8 (242.7 mg, 0.28 mmol, 81%) was obtained as a colorless oil: [α]_D = −16.6 (c = 0.53, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.83–7.80 (m, 2H, Ar), 7.76–7.72 (m, 2H, Ar), 7.39–7.12 (m, 25H, Ar), 5.09 (br dd, J = 1.9 Hz, ³J_PH = 8.8 Hz, 1H, 2-H), 4.94 (d, J = 11.4 Hz, 1H, OBn), 4.63 (d, J = 10.7 Hz, 1H, OBn), 4.62 (d, J = 12.9 Hz, 1H, OBn), 4.52 (d, J = 11.7 Hz, 1H, OBn), 4.52 (d, J = 11.7 Hz, 1H, OBn), 4.31 (d, J = 10.8 Hz, 1H, OBn), 4.08 (dd, J = 6.4, 6.4 Hz, 2H, 3’-H₂), 3.68 (br d, J = 3.2 Hz, 2H, 6-H₂), 3.63 (m, 2H, 3-H, 4-H), 3.56 (m, 1H, 1-H), 3.42 (m, 1H, 5-H), 1.86 (m, 1H, 2’-H_b), 1.81–1.73 (m, 2H, 1’-H_b, 2’-H_a), 1.68 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 163.5 (2 × C, CO), 150.9 (d, ²J_PC = 7.8 Hz, C, Ar), 150.7 (d, ²J_PC = 7.0 Hz, C, Ar), 138.5 (C, Ar), 138.4 (C, Ar), 137.8 (C, Ar), 134.4 (2 × CH, Ar), 129.7 (2 × CH, Ar), 129.3 (2 × CH, Ar), 129.0 (2 × C, Ar), 128.4 (2 × CH, Ar), 128.3 (4 × CH, Ar), 128.2 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.7 (2 × CH, Ar), 127.6 (CH, Ar), 127.5 (CH, Ar), 127.4 (CH, Ar), 125.2 (CH, Ar), 124.7 (CH, Ar), 123.4 (2 × CH, Ar), 120.4 (CH, Ar), 120.3 (CH, Ar), 120.23 (CH, Ar), 120.18 (CH, Ar), 82.0 (CH, C-3), 79.5 (CH, C-5), 77.9 (CH₂, C-3’), 77.0 (CH, C-2), 76.4 (d, ³J_PC = 5.6 Hz, CH, C-1), 75.1 (CH₂, OBn), 74.2 (CH, C-4), 73.4 (CH₂, OBn), 71.8 (CH₂, OBn), 69.3 (CH₂, C-6), 27.2 (CH₂, C-1’), 24.3 ppm (CH₂, C-2’). IR (CHCl₃): ν = 3013, 2869, 1789, 1733, 1193 cm^–1. MS (ESI) m/z (%) = 892 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₅₀H₄₈NNaO₁₁P 892.2863; found 892.2861. Anal. calcd for C₅₀H₄₈NO₁₁P: C, 69.04; H, 5.56; N, 1.61. Found: C, 68.94; H, 5.83; N, 1.67.

3-C-(3,4-Di-O-benzyl-2-O-diphenoxyphosphoryl-α-l-fucopyranosyl)1-propoxyphthalimide (10)

Following the general procedure starting from phthalimide 77 (253 mg, 0.48 mmol) and purification by column chromatography (hexanes–EtOAc, 7:3), product 10 (205 mg, 0.27 mmol, 56%) was obtained as a colorless oil: [α]_D = −19.6 (c = 0.43, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.83–7.80 (m, 2H, Ar), 7.75–7.73 (m, 2H, Ar), 7.37–7.13 (m, 20H, Ar), 4.91 (ddd, J = 6.3, 3.3 Hz, ³J_PH = 7.5 Hz, 1H, 2-H), 4.69 (d, J = 12.0 Hz, 1H, OBn), 4.66 (d, J = 12.0 Hz, 1H, OBn), 4.57 (d, J = 11.7 Hz, 1H, OBn), 4.42 (d, J = 11.7 Hz, 1H, OBn), 4.17–4.09 (m, 3H, 1-H, 3’-H₂), 4.01 (dddd, J = 6.7, 6.7, 6.7, 4.0 Hz, 1H, 5-H), 3.95 (dd, J = 6.3, 3.1 Hz, 1H, 3-H), 3.72 (dd, J = 4.1, 3.1 Hz, 1H, 4-H), 1.90–1.76 (m, 2H, 1’-H₂ or 2’-H₂), 1.74–1.60 (m, 2H, 1’-H₂ or 2’-H₂), 1.31 ppm (d, J = 6.7 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.5 (2 × C, CO), 150.52 (d, ²J_PC = 7.4 Hz, C, Ar), 150.48 (d, ²J_PC = 7.4 Hz, C, Ar), 138.3 (C, Ar), 138.1 (C, Ar), 134.4 (2 × CH, Ar), 129.7 (4 × CH, Ar), 128.9 (2 × C, Ar), 128.3 (2 × CH, Ar), 128.2 (2 × CH, Ar), 127.6 (4 × CH, Ar), 127.5 (2 × CH, Ar), 125.4 (CH, Ar), 125.3 (CH, Ar), 123.4 (2 × CH, Ar), 120.2 (CH, Ar), 120.12 (CH, Ar), 120.08 (CH, Ar), 120.0 (CH, Ar), 78.1 (CH₂, C-3’), 77.2 (CH, C-2), 76.1 (CH, C-3), 75.0 (CH, C-4), 73.1 (CH₂, OBn), 72.6 (CH₂, OBn), 69.2 (CH, C-5), 68.9 (CH, C-1), 24.7 (CH₂, C-1’), 24.1 (CH₂, C-2’), 14.8 ppm (CH₃, C-6). IR (CHCl₃): ν = 3027, 1791, 1733, 1214 cm^–1. MS (ESI) m/z (%) = 786 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₃H₄₂NNaO₁₀P 786.2444; found 786.2448. Anal. calcd for C₄₃H₄₂NO₁₀P: C, 67.62; H, 5.54; N, 1.83. Found: C, 67.81; H, 5.88; N, 1.48.

3-C-(2-O-Diphenoxyphosphoryl-3,5-di-O-1,1,3,3-tetraisopropyldisiloxanyl-α-d-ribofuranosyl)1-propoxyphthalimide (15)

Following the general procedure starting from phthalimide 88 (351 mg, 0.61 mmol) and purification by column chromatography (hexanes–EtOAc, 8:2 to 7:3), product 15 (443 mg, 0.55 mmol, 90%) was obtained as a colorless oil: [α]_D = +15.8 (c = 0.83, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.83–7.73 (m, 4H, Ar), 7.32–7.12 (m, 10H, Ar), 5.15 (ddd, J = 3.9, 2.9 Hz, ³J_PH = 7.9 Hz, 1H, 2-H), 4.47 (ddd, J = 9.1, 3.9 Hz, ⁴J_PH = 1.5 Hz, 1H, 3-H), 4.19 (m, 1H, 1-H), 4.08 (br dd, J = 6.3, 6.3 Hz, 2H, 3’-H₂), 3.99 (dd, J = 12.8, 3.1 Hz, 1H, 5-H_b), 3.94–3.90 (m, 2H, 4-H, 5-H_a), 1.88 (m, 1H, 2’-H_b), 1.71 (m, 1H, 2’-H_a), 1.65–1.57 (m, 2H, 1’-H₂), 1.10–0.97 ppm (m, 28H, ⁱPr). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.6 (2 × C, CO), 150.9 (d, ²J_PC = 7.4 Hz, C, Ar), 150.6 (d, ²J_PC = 6.4 Hz, C, Ar), 134.4 (2 × CH, Ar), 129.7 (2 × CH, Ar), 129.6 (2 × CH, Ar), 129.0 (2 × C, Ar), 125.2 (CH, Ar), 125.0 (CH, Ar), 123.4 (2 × CH, Ar), 120.23 (CH, Ar), 120.18 (CH, Ar), 120.05 (CH, Ar), 120.00 (CH, Ar), 81.5 (d, ²J_PC = 6.4 Hz, CH, C-2), 79.6 (CH, C-4), 78.9 (d, ³J_PC = 5.3 Hz, CH, C-1), 77.9 (CH₂, C-3’), 71.7 (CH, C-3), 61.0 (CH₂, C-5), 26.1 (CH₂, C-1’), 24.6 (CH₂, C-2’), 17.4 (CH₃, ⁱPr), 17.3 (CH₃, ⁱPr), 17.28 (CH₃, ⁱPr), 17.26 (CH₃, ⁱPr), 17.04 (CH₃, ⁱPr), 17.01 (CH₃, ⁱPr), 16.8 (CH₃, ⁱPr), 16.7 (CH₃, ⁱPr), 13.5 (CH, ⁱPr), 13.1 (CH, ⁱPr), 12.7 (CH, ⁱPr), 12.4 ppm (CH, ⁱPr). IR (CHCl₃): ν = 2948, 1791, 1733, 1490, 1212 cm^–1. MS (ESI) m/z (%) = 834 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₅₄NNaO₁₁PSi₂ 834.2871; found 834.2874. Anal. calcd for C₄₀H₅₄NO₁₁PSi₂: C, 59.17; H, 6.70; N, 1.72. Found: C, 59.00; H, 6.94; N, 1.67.

3-C-(2-O-Diphenoxyphosphoryl-β-d-arabinopyranosyl)1-propoxyphthalimide (12)

Compound 11 (227 mg, 0.35 mmol) was dissolved in CH₂Cl₂ (1.6 mL), and TFA/H₂O (230 μL, 80%) was dropwise added at 0 °C. After 1 h, the mixture was neutralized with a saturated aqueous solution of NaHCO₃ and extracted with CH₂Cl₂. The organic extracts were dried over Na₂SO₄ and concentrated under reduced pressure. Column chromatography of the residue (hexanes–EtOAc, 3:7) gave 12 (161.7 mg, 0.28 mmol, 81%) as a colorless oil: [α]_D = +4.6 (c = 0.56, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.83–7.80 (m, 2H, Ar), 7.75–7.72 (m, 2H, Ar), 7.35–7.17 (m, 10H, Ar), 4.60 (ddd, J = 4.1, 1.3 Hz, ³J_PH = 8.2 Hz, 1H, 2-H), 4.16–4.05 (m, 3H, 3-H, 3’-H₂), 3.86–3.81 (m, 2H, 1-H, 4-H), 3.74 (dd, J = 11.1, 5.1 Hz, 1H, 5-H_b), 3.48 (dd, J = 10.7, 10.7 Hz, 1H, 5-H_a), 2.75 (br d, J = 8.2 Hz, 1H, OH), 2.01 (br s, 1H, OH), 1.86 (m, 1H, 2’-H_b), 1.75 (m, 1H, 2’-H_a), 1.68 (m, 1H, 1’-H_b), 1.58 ppm (m, 1H, 1’-H_a). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.6 (2 × C, CO), 150.3 (d, ²J_PC = 7.4 Hz, C, Ar), 150.2 (d, ²J_PC = 8.4 Hz, C, Ar), 134.4 (2 × CH, Ar), 129.9 (4 × CH, Ar), 128.9 (2 × C, Ar), 125.7 (CH, Ar), 125.6 (CH, Ar), 123.5 (2 × CH, Ar), 120.09 (CH, Ar), 120.06 (CH, Ar), 120.04 (CH, Ar), 120.00 (CH, Ar), 79.1 (d, ²J_PC = 6.4 Hz, CH, C-2), 78.0 (CH₂, C-3’), 72.4 (d, ³J_PC = 6.4 Hz, CH, C-1), 68.0 (CH, C-3), 65.9 (CH₂, C-5), 64.2 (CH, C-4), 26.0 (CH₂, C-1’), 24.5 ppm (CH₂, C-2’). IR (CHCl₃): ν = 3688, 3557, 3393, 3026, 1790, 1733, 1211 cm^–1. MS (ESI) m/z (%) = 592 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₈H₂₈NNaO₁₀P 592.1349; found 592.1341. Anal. calcd for C₂₈H₂₈NO₁₀P: C, 59.05; H, 4.96; N, 2.46. Found: C, 59.26; H, 4.99; N, 2.48.

General Procedure to Give Acetyl Derivatives 90 and 97

The corresponding alcohol (1 mmol) was dissolved in dry pyridine (3.7 mL), and Ac₂O (1.2 mL) and DMAP (13.7 mg, 0.11 mmol) were added. The reaction was stirred at room temperature for 0.5 h, and then it was evaporated in a high vacuum rotovap, quenched with an aqueous solution of HCl 10%, and extracted with CH₂Cl₂. The combined organic extracts were dried over Na₂SO₄ and concentrated under reduced pressure. Column chromatography of the residue (hexanes–EtOAc) gave the acetyl derivative.

Methyl 4-O-Acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-glucopyranoside (90)

Following the general procedure starting from methyl 6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-glucopyranoside (89)⁶⁴ (119.7 mg, 0.27 mmol) and purification by column chromatography (hexanes–EtOAc, 7:3), product 90 (122.7 mg, 0.25 mmol, 94%) was obtained as a colorless oil: [α]_D = +65.3 (c = 0.80, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.69–7.67 ppm (m, 4H, Ar), 7.45–7.36 (m, 6H, Ar), 4.87 (d, J = 3.5 Hz, 1H, 1-H), 4.87 (dd, J = 9.5, 9.5 Hz, 1H, 4-H), 3.75 (ddd, J = 10.1, 5.7, 2.5 Hz, 1H, 5-H), 3.71–3.62 (m, 2H, 6-H₂), 3.58 (dd, J = 9.5, 9.5 Hz, 1H, 3-H), 3.54 (s, 3H, OMe), 3.51 (s, 3H, OMe), 3.47 (s, 3H, OMe), 3.30 (dd, J = 9.6, 3.7 Hz, 1H, 2-H), 1.95 (s, 3H, OAc), 1.05 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 169.5 (C, OAc), 135.7 (2 × CH, Ar), 135.6 (2 × CH, Ar), 133.4 (C, Ar), 133.3 (C, Ar), 129.62 (CH, Ar), 129.60 (CH, Ar), 127.62 (2 × CH, Ar), 127.59 (2 × CH, Ar), 97.3 (CH, C-1), 81.5 (CH, C-2 or C-5), 81.1 (CH, C-2 or C-5), 70.6 (CH, C-3 or C-4), 70.5 (CH, C-3 or C-4), 63.2 (CH₂, C-6), 60.6 (CH₃, OMe), 59.1 (CH₃, OMe), 55.1 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 20.8 (CH₃, OAc), 19.2 ppm (C, DPS). IR (CHCl₃): ν = 2932, 1748, 1233, 1046 cm^–1. MS (ESI) m/z (%) = 525 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₇H₃₈NaO₇Si 525.2285; found 525.2272. Anal. calcd for C₂₇H₃₈O₇Si: C, 64.51; H, 7.62. Found: C, 64.45; H, 7.85.

Methyl 4-O-Acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-galactopyranoside (97)

Following the general procedure starting from methyl 6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-galactopyranoside (96)⁶⁴ (2.15 g, 4.80 mmol) and purification by column chromatography (hexanes–EtOAc, 7:3), product 97 (2.19 g, 4.36 mmol, 91%) was obtained as a colorless oil: [α]_D = +65.5 (c = 1.45, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.69–7.64 (m, 4H, Ar), 7.45–7.36 (m, 6H, Ar), 5.58 (dd, J = 3.2, 1.0 Hz, 1H, 4-H), 4.88 (d, J = 3.6 Hz, 1H, 1-H), 3.93 (ddd, J = 6.9, 6.9, 0.9 Hz, 1H, 5-H), 3.69 (dd, J = 10.2, 6.3 Hz, 1H, 6-H_b), 3.64 (dd, J = 10.4, 7.0 Hz, 1H, 6-H_a), 3.60 (dd, J = 10.1, 3.4 Hz, 1H, 3-H), 3.51 (s, 3H, OMe), 3.50 (dd, J = 10.1, 6.4 Hz, 1H, 2-H), 3.43 (s, 3H, OMe), 3.40 (s, 3H, OMe), 2.03 (s, 3H, OAc), 1.06 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 169.9 ppm (C, OAc), 135.5 (4 × CH, Ar), 133.2 (C, Ar), 133.1 (C, Ar), 129.7 (CH, Ar), 129.6 (CH, Ar), 127.7 (2 × CH, Ar), 127.6 (2 × CH, Ar), 97.7 (CH, C-1), 78.1 (CH, C-2 or C-5), 77.3 (CH, C-2 or C-5), 69.2 (CH, C-3 or C-4), 66.9 (CH, C-3 or C-4), 62.2 (CH₂, C-6), 59.0 (CH₃, OMe), 57.6 (CH₃, OMe), 55.2 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 20.6 (CH₃, OAc), 19.0 ppm (C, DPS). IR (CHCl₃): ν = 2934, 1741, 1239, 1106 cm^–1. MS (ESI) m/z (%) = 525 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₇H₃₈NaO₇Si 525.2285; found 525.2279. Anal. calcd for C₂₇H₃₈O₇Si: C, 64.51; H, 7.62. Found: C, 64.72; H, 7.50.

General Procedure to Give Allenyl Derivatives 91, 98, and 107

The precursor (1 mmol) was dissolved in CH₃CN (11 mL) under a N₂ atmosphere, and freshly prepared propargyl trimethylsilane/Et₂O⁶⁵ 39% v/v (0.77 mL, 2 mmol) and TMSOTf (0.4 mL, 2.27 mmol) were dropwise added. The reaction was sonicated in an ultrasonic bath for 1.5–3 h, and then it was poured over a saturated aqueous solution of NaHCO₃ and extracted with EtOAc. The organic phase was dried over Na₂SO₄, filtered, and evaporated. The crude was dissolved in DMF (2 mL), and DPSCl (176 μL, 38.68 mmol) and imidazole (102 mg, 22.42 mmol) were added. The reaction was stirred at room temperature for 2 h, evaporated under reduced high pressure, and purified by column chromatography (hexanes–EtOAc) to give the expected allenyl derivative.

C-(4-O-Acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-glucopyranosyl)allene (91)

Following the general procedure starting from 90 (2.23 g, 4.55 mmol) and purification by column chromatography (hexanes–EtOAc, 9:1), product 91 (991.3 mg, 1.79 mmol, 39%) was obtained as a colorless oil: [α]_D = +91.4 (c = 0.80, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.70–7.66 (m, 4H, Ar), 7.44–7.35 (m, 6H, Ar), 5.38 (ddd, J = 6.7, 6.7, 6.7 Hz, 1H, 1’-H), 4.93 (dd, J = 9.2, 9.2 Hz, 1H, 3-H), 4.87 (dd, J = 6.7, 0.0 Hz, 1H, 3’-H_b), 4.86 (dd, J = 6.7, 0.0 Hz, 1H, 3’-H_a), 4.78 (m, 1H, 1-H), 3.85–3.80 (m, 2H, 4-H, 6-H_b), 3.69–3.67 (m, 2H, 5-H, 6-H_a), 3.51 (s, 3H, OMe), 3.48 (s, 3H, OMe), 3.43 (dd, J = 9.5, 6.3 Hz, 1H, 2-H), 1.96 (s, 3H, OAc), 1.06 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 209.5 (C, C-2’), 169.5 (C, OAc), 135.7 (4 × CH, Ar), 133.6 (C, Ar), 133.4 (C, Ar), 129.6 (CH, Ar), 129.5 (CH, Ar), 127.57 (2 × CH, Ar), 127.55 (2 × CH, Ar), 85.5 (CH, C-1’), 81.0 (2 × CH, C-2, C-5), 76.7 (CH₂, C-3’), 72.8 (CH, C-4), 71.1 (CH, C-1), 70.5 (CH, C-3), 63.6 (CH₂, C-6), 60.0 (CH₃, OMe), 58.4 (CH₃, OMe), 26.8 (3 × CH₃, DPS), 20.9 (CH₃, OAc), 19.2 ppm (C, DPS). IR (CHCl₃): ν = 3024, 2934, 1956, 1736, 1208 cm^–1. MS (ESI) m/z (%) = 533 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₉H₃₈NaO₆Si 533.2335; found 533.2333.

C-(4-O-Acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-galactopyranosyl)allene (98)

Following the general procedure starting from 97 (1.91 g, 3.80 mmol) and purification by column chromatography (hexanes–EtOAc, 8:2), product 98 (1.27 g, 2.49 mmol, 59%) was obtained as a yellow oil: [α]_D = +101.0 (c = 0.81, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.68–7.63 (m, 4H, Ar), 7.45–7.35 (m, 6H, Ar), 5.67 (dd, J = 2.9, 1.2 Hz, 1H, 4-H), 5.33 (m, 1H, 1’-H), 4.85–4.79 (m, 3H, 1-H, 3’-H₂), 3.98 (ddd, J = 7.6, 5.7, 1.5 Hz, 1H, 5-H), 3.67 (dd, J = 10.1, 5.8 Hz, 1H, 6-H_b), 3.66 (dd, J = 10.5, 5.7 Hz, 1H, 2-H), 3.59 (dd, J = 9.8, 7.9 Hz, 1H, 6-H_a), 3.47 (s, 3H, OMe), 3.46 (s, 3H, OMe), 3.40 (dd, J = 9.9, 3.6 Hz, 1H, 3-H), 2.06 (s, 3H, OAc), 1.06 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 209.0 (C, C-2’). 169.8 (C, OAc), 135.60 (2 × CH, Ar), 135.56 (2 × CH, Ar), 133.4 (C, Ar), 133.2 (C, Ar), 129.72 (CH, Ar), 129.67 (CH, Ar), 127.7 (2 × CH, Ar), 127.6 (2 × CH, Ar), 85.2 (CH, C-1’), 78.8 (CH, C-5), 77.1 (CH, C-2), 76.9 (CH₂, C-3’), 71.5 (CH, C-4), 71.0 (CH, C-1), 66.6 (CH, C-3), 61.8 (CH₂, C-6), 58.5 (CH₃, OMe), 57.7 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 20.7 (CH₃, OAc), 19.1 ppm (C, DPS). IR (CHCl₃): ν = 3016, 2934, 1955, 1741, 1208 cm^–1. MS (ESI) m/z (%) = 533 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₉H₃₈NaO₆Si 533.2335; found 533.2328. Anal. calcd for C₂₉H₃₈O₆Si: C, 68.20; H, 7.50. Found: C, 68.24; H, 7.70.

C-(2,3,4-Tri-O-acetyl-α-l-fucopyranosyl)allene (107)

Following the general procedure starting from peracetyl l-fucose (106) (877 mg, 2.64 mmol) and purification by column chromatography (hexanes–EtOAc, 8:2), product 107 (601.8 mg, 1.93 mmol, 73%) was obtained as a yellow oil: [α]_D = −170.0 (c = 0.92, CHCl₃). ¹H NMR (500 MHz, C₆D₆) δ_H 5.68 (dd, J = 11.0, 6.0 Hz, 1H, 2-H), 5.46 (dd, J = 11.0, 3.5 Hz, 1H, 3-H), 5.37 (dd, J = 3.5, 1.3 Hz, 1H, 4-H), 5.17 (ddd, J = 6.9, 6.9, 6.9 Hz, 1H, 1′-H), 5.04 (dddd, J = 6.1, 6.1, 3.2, 3.2 Hz, 1H, 1-H), 4.59 (ddd, J = 11.3, 6.6, 3.2 Hz, 1H, 3′-H_b), 4.55 (ddd, J = 11.7, 6.9, 3.5 Hz, 1H, 3′-H_a), 3.67 (dddd, J = 6.3, 6.3, 6.3, 1.0 Hz, 1H, 5-H), 1.75 (s, 3H, OAc), 1.65 (s, 3H, OAc), 1.59 (s, 3H, OAc), 0.97 ppm (d, J = 6.3 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, C₆D₆) δ_C 209.8 (CH, C-2’), 170.2 (C, OAc), 169.8 (C, OAc), 169.4 (C, OAc), 85.4 (CH, C-1’), 76.6 (CH₂, C-3’), 71.7 (CH, C-1), 71.5 (CH, C-4), 69.1 (CH, C-3), 68.4 (CH, C-2), 66.6 (CH, C-5), 20.4 (CH₃, OAc), 20.2 (CH₃, OAc), 20.0 (CH₃, OAc), 16.3 ppm (CH₃, C-6). IR (CHCl₃): ν = 2989, 2944, 1957, 1750, 1373, 1230, 1062 cm^–1. MS (ESI) m/z (%) = 335 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₅H₂₀NaO₇ 335.1107; found 335.1101. Anal. calcd for C₁₅H₂₀O₇: C, 57.69; H, 6.45. Found: C, 58.07; H, 6.79.

C-(2,3,4-Tri-O-acetyl-α-l-rhamnopyranosyl)allene (101) and C-(2,3,4-Tri-O-acetyl-β-l-rhamnopyranosyl)allene (102)

BF₃•OEt₂ (6.40 mL, 51.86 mmol) and TMSOTf (6.20 mL, 34.66 mmol) were dropwise added to a solution of peracetyl l-rhamnose (100) (6 g, 18.0 mmol) and fresly prepared propargyl trimethylsilane (5.11 mL, 34.28 mmol) in dry CH₃CN (39 mL) at 0 °C, and the mixture was stirred at room temperature for 15 h. Then, it was poured over HCl 10% and extracted with EtOAc. The organic extracts were washed with saturated aqueous solutions of NaHCO₃ and NaCl, dried over Na₂SO₄, and concentrated to dryness under reduced pressure. Column chromatography of the residue (hexanes–EtOAc, 95:5) gave 101 (3.80 g, 12.18 mmol, 67%) and 102 (1.40 g, 4.49 mmol, 25%) that could not be completely purified and was isolated as a mixture (1:1) with 101. Compound 101: colorless oil, [α]_D = −16.7 (c = 0.42, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 5.40 (dd, J = 3.3, 2.0 Hz, 1H, 2-H), 5.26 (dd, J = 9.8, 3.5 Hz, 1H, 3-H), 5.21 (ddd, J = 6.8, 6.8, 4.4 Hz, 1H, 1′-H), 5.07 (dd, J = 9.5, 9.5 Hz, 1H, 4-H), 5.05 (ddd, J = 12.3, 6.9, 4.1 Hz, 1H, 3′-H_b), 4.99 (ddd, J = 11.4, 6.9, 4.4 Hz, 1H, 3′-H_a), 4.57 (dddd, J = 4.1, 4.1, 4.1, 1.9 Hz, 1H, 1-H), 3.84 (dddd, J = 9.5, 6.2, 6.2, 6.2 Hz, 1H, 5-H), 2.14 (s, 3H, OAc), 2.04 (s, 3H, OAc), 1.97 (s, 3H, OAc), 1.21 ppm (d, J = 6.0 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 207.7 (CH, C-2’), 170.3 (C, OAc), 170.0 (C, OAc), 169.9 (C, OAc), 87.8 (CH, C-1’), 78.7 (CH₂, C-3’), 73.3 (CH, C-1), 71.6 (CH, C-4), 70.3 (CH, C-2), 69.3 (CH, C-3), 68.8 (CH, C-5), 21.0 (CH₃, OAc), 20.8 (CH₃, OAc), 20.6 (CH₃, OAc), 17.6 ppm (CH₃, C-6). IR (CHCl₃): ν = 2981, 2933, 1955, 1746, 1369, 1221 cm^–1. MS (ESI) m/z (%) = 335 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₅H₂₀NaO₇ 335.1107; found 335.1107. Anal. calcd for C₁₅H₂₀O₇: C, 57.69; H, 6.45. Found: C, 58.07; H, 6.79. Compound 102: ¹H NMR (500 MHz, CDCl₃, signals taken from a spectrum of the mix of 101 and 102) δ_H 5.39 (dd, J = 2.9, 1.3 Hz, 1H, 2-H), 5.14 (ddd, J = 6.6, 6.6, 6.6 Hz, 1H, 1′-H), 5.05 (m, 1H, 3-H), 4.98 (dd, J = 6.7, 4.4 Hz, 1H, 4-H), 4.86 (ddd, J = 11.4, 6.6, 2.2 Hz, 1H, 3′-H_b), 4.81 (ddd, J = 11.7, 6.9, 2.2 Hz, 1H, 3′-H_a), 4.19 (dddd, J = 6.9, 2.2, 2.2, 1.3 Hz, 1H, 1-H), 3.54 (dddd, J = 9.1, 6.3, 6.3, 6.3 Hz, 1H, 5-H), 2.15 (s, 3H, OAc), 2.04 (s, 3H, OAc), 1.96 (s, 3H, OAc), 1.25 ppm (d, J = 6.3 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃, signals taken from a spectrum of the mix of 101 and 102) δ_C 208.4 (CH, C-2’), 170.4 (C, OAc), 170.3 (C, OAc), 169.9 (C, OAc), 87.3 (CH, C-1’), 77.4 (CH₂, C-3’), 75.1 (CH, C-1), 74.6 (CH, C-5), 72.3 (CH, C-4), 70.6 (CH, C-3), 70.4 (CH, C-2), 21.0 (CH₃, OAc), 20.7 (CH₃, OAc), 20.6 (CH₃, OAc), 17.7 ppm (CH₃, C-6). IR (CHCl₃): ν = 2981, 2937, 1959, 1750, 1373, 1225, 1054 cm^–1. MS (ESI) m/z (%) = 335 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₅H₂₀NaO₇ 335.1107; found 335.1107.

C-(4-O-Benzyl-2,3-O-isopropylidene-α-l-rhamnopyranosyl)allene (103)

To a solution of 101 (1.89 g, 6.06 mmol) in dry MeOH (45 mL) was added K₂CO₃ (1.35 g, 9.78 mmol), and the mixture was stirred at room temperature for 3 h. Then, it was filtered and neutralized with the Amberlyst 15 H⁺ ion exchange resin. It was filtered again under vacuum and evaporated. The resulting organic crude was dissolved in acetone (60 mL), and 2,2-dimethoxypropane (1.9 mL, 15.15 mmol) and p-TsOH·H₂O (692 mg, 3.64 mmol) were subsequently added while stirring at room temperature for 3 h. The acetone was evaporated, and the residue was poured over a saturated aqueous solution of NaHCO₃ and extracted with CH₂Cl₂. The organic phase was dried over Na₂SO₄ and concentrated to dryness under reduced pressure. The organic crude was dissolved in dry DMF (73 mL) under a N₂ atmosphere, and NaH 60% in mineral oil (364 mg, 9.09 mmol) was slowly added at 0 °C. After 20 min, BnBr (1.4 mL, 12.12 mmol) was dropwise added and stirring was continued at 0 °C for 3 h. Ice-water was used to destroy the excess of NaH, and the mixture was evaporated in a high vacuum rotovap, poured over a saturated solution of NH₄Cl, and extracted with CH₂Cl₂. The combined extracts were dried over Na₂SO₄ and concentrated to dryness under reduced pressure. Column chromatography of the residue (hexanes–EtOAc, 95:5) gave 103 (1.03 g, 3.27 mmol, 54%) as a yellow oil: [α]_D = +37.0 (c = 0.74, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.36–7.24 (m, 5H, Ar), 5.23 (ddd, J = 7.0, 7.0, 5.1 Hz, 1H, 1’-H), 4.90–4.86 (m, 3H, OBn, 3’-H₂), 4.73 (m, 1H, 1-H), 4.62 (d, J = 11.7 Hz, 1H, OBn), 4.29 (dd, J = 5.4, 1.6 Hz, 1H, 2-H), 4.19 (dd, J = 7.0, 5.6 Hz, 1H, 3-H), 3.61 (dddd, J = 9.5, 6.0, 6.0, 6.0 Hz, 1H, 5-H), 3.26 (dd, J = 9.8, 7.3 Hz, 1H, 4-H), 1.52 (s, 3H, Me), 1.37 (s, 3H, Me), 1.26 ppm (d, J = 6.3 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 208.0 (C, C-2’), 138.2 (C, Ar), 128.1 (2 × CH, Ar), 127.9 (2 × CH, Ar), 127.5 (CH, Ar), 108.6 (C, isopropylidene), 89.5 (CH, C-1’), 81.5 (CH, C-4), 78.0 (CH, C-3), 77.4 (CH₂, C-3’), 75.5 (CH, C-2), 72.9 (CH₂, OBn), 70.7 (CH, C-1), 67.0 (CH, C-5), 28.0 (CH₃, Me), 26.3 (CH₃, Me), 18.0 ppm (CH₃, C-6). IR (CHCl₃): ν = 3016, 2993, 1955, 1228, 1074 cm^–1. MS (ESI) m/z (%) = 339 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₉H₂₄NaO₄ 339.1572; found 339.1567. Anal. calcd for C₁₉H₂₄O₄: C, 72.13; H, 7.65. Found: C, 72.06; H, 7.74.

C-(2,3-O-[(2S,3S)-2,3-Dimethoxybutane-2,3-diyl]-α-l-fucopyranosyl)allene (108)

To a solution of 107 (5.07 g, 16.25 mmol) in dry MeOH (244 mL) was added K₂CO₃ (3.6 g, 26 mmol), and the mixture was stirred at room temperature for 3 h. Then, it was filtered and neutralized with the Amberlyst 15 H⁺ ion exchange resin. It was filtered again under vacuum and evaporated. The resulting organic crude was dissolved in dry MeOH (81.3 mL), and 2,3-butanedione (2.85 mL, 32.5 mmol), (MeO)₃CH (7.1 mL, 65 mmol), and BF₃•Et₂O (3.4 mL, 30.88 mmol) were added dropwise. The mixture was stirred at 60 °C for 4.5 h. A few pipettes of Et₃N were added while stirring at room temperature for 15 min. Then, it was evaporated to dryness. Column chromatography of the residue (hexanes–EtOAc, 7:3) gave 108 (3.18 g, 10.6 mmol, 65%) as a colorless oil: [α]_D = −16.9 (c = 1.15, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 5.38 (ddd, J = 6.8, 6.8, 4.4 Hz, 1H, 1’-H), 4.85 (dd, J = 6.9, 4.1 Hz, 2H, 3’-H₂), 4.61 (dddd, J = 6.0, 4.1, 4.1, 4.1 Hz, 1H, 1-H), 4.29 (dd, J = 10.6, 6.0 Hz, 1H, 2-H), 4.00 (dddd, J = 6.3, 6.3, 6.3, 0.0 Hz, 1H, 5-H), 3.85 (dd, J = 10.6, 3.1 Hz, 1H, 3-H), 3.72 (br s, 1H, 4-H), 3.24 (s, 3H, OMe), 3.23 (s, 3H, OMe), 2.39 (br s, 1H, OH), 1.31 (s, 3H, Me), 1.26 (d, J = 6.3 Hz, 3H, 6-H₃), 1.25 ppm (s, 3H, Me). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 208.7 (C, C-2’), 100.1 (C), 99.8 (C), 85.8 (CH, C-1’), 77.0 (CH₂, C-3’), 71.5 (CH, C-1), 70.8 (CH, C-4), 68.4 (CH, C-5), 67.9 (CH, C-3), 64.0 (CH, C-2), 47.9 (2 × CH₃, 2 × OMe), 17.6 (2 × CH₃, Me, C-6), 16.5 ppm (CH₃, Me). IR (CHCl₃): ν = 3672, 3583, 3010, 2942, 1957, 1226 cm^–1. MS (ESI) m/z (%) = 323 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₅H₂₄NaO₆ 323.1471; found 323.1476. Anal. calcd for C₁₅H₂₄O₆: C, 59.98; H, 8.05. Found: C, 59.90; H, 8.35.

General Procedure to Give Diphenoxyphosphoryl Derivatives 92, 95, and 99

The corresponding alcohol (1 mmol) in dry CH₂Cl₂ (58 mL) was treated with DMAP (562 mg, 4.61 mmol) and ClPO(OPh)₂ (0.95 mL, 4.61 mmol) at room temperature for 2 h. The reaction was quenched with a saturated aqueous solution of NH₄Cl and extracted with CH₂Cl₂. The organic phase was dried over Na₂SO₄, filtered, and evaporated. Column chromatography of the residue (hexanes–EtOAc) gave the diphenoxyphosphoryl derivatives.

C-(6-O-tert-Butyldiphenylsilyl-4-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-d-glucopyranosyl)allene (92)

To a solution of the allene 91 (97.4 mg, 0.19 mmol) in dry MeOH (0.95 mL) was added K₂CO₃ (2.1 mg, 0.015 mmol), and the mixture was stirred at room temperature overnight. The residue was evaporated to afford the intermediate alcohol that was submitted to the general procedure to give the diphenoxylphosphoryl derivative for 2.5 h. Column chromatography (hexanes–EtOAc, 85:15) gave 92 (96.5 mg, 0.14 mmol, 73%) as a colorless oil: [α]_D = +45.6 (c = 0.45, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.68–7.07 (m, 20H, Ar), 5.36 (ddd, J = 8.3, 8.3, 8.3 Hz, 1H, 1’-H), 4.84 (dd, J = 8.6, 0.0 Hz, 1H, 3’-H_b), 4.83 (dd, J = 8.4, 0.0 Hz, 1H, 3’-H_a), 4.74 (m, 1H, 1-H), 4.62 (ddd, J = 8.5, 8.5 Hz, ³J_PH = 8.5 Hz, 1H, 4-H), 3.96–3.87 (m, 2H, 5-H, 6-H_b), 3.79 (dd, J = 14.9, 6.7 Hz, 1H, 6-H_a), 3.57 (dd, J = 10.9, 8.3 Hz, 1H, 3-H), 3.46 (m, 1H, 2-H), 3.45 (s, 6H, OMe), 1.04 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 209.6 (C, C-2’), 150.8 (d, ²J_PC = 7.0 Hz, C, Ar), 150.6 (d, ²J_PC = 7.8 Hz, C, Ar), 133.6 (2 × C, Ar), 119.9–135.7 (20 × CH, Ar), 85.2 (CH, C-1’), 81.6 (CH, C-2), 81.1 (CH, C-3), 76.7 (CH₂, C-3’), 76.6 (CH, C-4), 72.8 (d, ³J_PC = 7.0 Hz, CH, C-5), 70.9 (CH, C-1), 63.0 (CH₂, C-6), 60.2 (CH₃, OMe), 58.2 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 19.3 ppm (C, DPS). IR (CHCl₃): ν = 3015, 2933, 1955, 1592, 1490, 1191 cm^–1. MS (ESI) m/z (%) = 723 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₉H₄₅NaO₈PSi 723.2519; found 723.2510. Anal. calcd for C₃₉H₄₅O₈Psi: C, 66.84; H, 6.47. Found: C, 66.90; H, 6.42.

C-(4,6-Bis-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-d-glucopyranosyl)methanol (95)

Compound 48 (620 mg, 1.24 mmol) was dissolved in CH₂Cl₂ (6.2 mL), and DHP (282 μL, 3.09 mmol) and p-TsOH·H₂O (15 mg, 0.08 mmol) were added while stirring at room temperature for 2 h. The reaction was poured over a saturated aqueous solution of NaHCO₃ and extracted with CH₂Cl₂. The organic extract was dried over Na₂SO₄, filtered, and evaporated. The crude in dry THF (25 mL) was treated with TBAF/THF 1 M solution (1.9 mL, 1.9 mmol) for 3 h at room temperature. Then, the mixture was evaporated to dryness and quickly chromatographed (hexanes–EtOAc 3:7) to obtain the corresponding alcohol (315 mg, 0.91 mmol, 73%) as an orange oil that was saponified with K₂CO₃ (25 mg, 0.18 mmol) in MeOH (4.6 mL) at room temperature for 4 h, filtered over a pad of Celite, and concentrated. The resulting diol was treated with ClPO(OPh)₂ (1.7 mL, 8.19 mmol) and dry pyridine (9.1 mL, 112.5 mmol) at room temperature overnight. The reaction was evaporated in a high vacuum rotovap, quenched with an aqueous solution of HCl 10%, and extracted with CH₂Cl₂. The organic phase was washed with a saturated aqueous solution of NaHCO₃, dried over Na₂SO₄, and evaporated. Finally, the THP protecting group was hydrolyzed by treatment with p-TsOH·H₂O (17.3 mg, 0.091 mmol) in MeOH (1.8 mL) at room temperature for 2 h. The mixture was poured over a saturated aqueous solution of NaHCO₃ and extracted with CH₂Cl₂. The organic phase was dried over Na₂SO₄, filtered, and evaporated. Column chromatography of the residue (hexanes–EtOAc, 4:6) gave 95 (315.3 mg, 0.46 mmol, 37% overall yield) as a colorless oil: [α]_D = +20.6 (c = 1.25, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.34–7.11 (m, 20H, Ar), 4.33–4.20 (m, 3H, 4-H, 6-H₂), 4.14–4.09 (m, 2H, 1-H, 5-H), 3.90 (dd, J = 12.6, 8.8 Hz, 1H, 1’-H_b), 3.70 (dd, J = 12.6, 3.5 Hz, 1H, 1’-H_a), 3.51 (dd, J = 8.2, 8.2 Hz, 1H, 3-H), 3.42 (s, 6H, 2 × OMe), 3.40 ppm (dd, J = 8.2, 5.7 Hz, 1H, 2-H), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.7 (d, ²J_PC = 7.4 Hz, C, Ar), 150.6 (d, ²J_PC = 7.4 Hz, C, Ar), 150.5 (d, ²J_PC = 7.4 Hz, C, Ar), 150.3 (d, ²J_PC = 7.4 Hz, C, Ar), 120.0–129.8 (20 × CH, Ar), 80.4 (2 × CH, C-2, C-3), 75.9 (d, ²J_PC = 6.4 Hz, CH, C-4), 74.1 (CH, C-1), 70.9 (CH, C-5), 68.3 (d, ²J_PC = 7.4 Hz, CH₂, C-6), 60.3 (CH₃, OMe), 58.8 (CH₃, OMe), 58.3 ppm (CH₂, C-1’). IR (CHCl₃): ν = 3690, 3620, 3024, 2401, 1491, 1226 cm^–1. MS (ESI) m/z (%) = 709 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₃H₃₆NaO₁₂P₂ 709.1580; found 709.1582. Anal. calcd for C₃₃H₃₆O₁₂P₂: C, 57.73; H, 5.28. Found: C, 57.82; H, 5.62.

C-(6-O-tert-Butyldiphenylsilyl-4-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-d-galactopyranosyl)allene (99)

To a solution of the acetyl derivative 98 (749.5 mg, 1.47 mmol) in MeOH (7.3 mL) was added K₂CO₃ (16.2 mg, 0.12 mmol), and it was stirred at room temperature overnight. The mixture was filtered, evaporated, and submitted to the general procedure to give the diphenoxyphosphoryl derivative. Column chromatography (hexanes–EtOAc, 8:2) of the residue afforded 99 (928.6 mg, 1.32 mmol, 90%) as a colorless oil: [α]_D = +74.6 (c = 0.46, CHCl₃). ¹H NMR (400 MHz, CDCl₃) δ_H 7.08–7.65 (m, 20H, Ar), 5.28–5.24 (m, 2H, 1-H, 1’-H), 4.79–4.67 (m, 3H, 4-H, 3’-H₂), 3.85 (m, 1H, 5-H), 3.79 (dd, J = 10.1, 7.4 Hz, 1H, 6-H_b), 3.69 (dd, J = 10.1, 6.1 Hz, 1H, 6-H_a), 3.61 (dd, J = 9.6, 5.6 Hz, 1H, 3-H), 3.41 (s, 3H, OMe), 3.38 (s, 3H, OMe), 3.32 (dd, J = 9.6, 1.3 Hz, 1H, 2-H), 1.03 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 208.8 (C, C-2’), 150.8 (d, ²J_PC = 7.8 Hz, C, Ar), 150.7 (d, ²J_PC = 7.1 Hz, C, Ar), 135.61 (2 × CH, Ar), 135.56 (2 × CH, Ar), 133.5 (C, Ar), 133.3 (C, Ar), 129.8 (CH, Ar), 129.7 (CH, Ar), 129.6 (2 × CH, Ar), 129.3 (2 × CH, Ar), 127.64 (2 × CH, Ar), 127.59 (2 × CH, Ar), 125.0 (CH, Ar), 124.9 (CH, Ar), 120.52 (CH, Ar), 120.45 (CH, Ar), 120.12 (CH, Ar), 120.07 (CH, Ar), 85.3 (CH, C-1’), 79.1 (CH, C-2), 76.7 (CH₂, C-3’), 76.7 (CH, C-3), 74.5 (d, ²J_PC = 6.3 Hz, CH, C-4), 71.7 (d, ³J_PC = 5.6 Hz, CH, C-5), 71.3 (CH, C-1), 62.1 (CH₂, C-6), 59.0 (CH₃, OMe), 57.5 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 19.1 ppm (C, DPS). IR (CHCl₃): ν = 3016, 2933, 1956, 1592, 1490, 1112 cm^–1. MS (ESI) m/z (%) = 723 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₉H₄₅NaO₈PSi 723.2519; found 723.2513. Anal. calcd for C₃₉H₄₅O₈PSi: C, 66.84; H, 6.47. Found: C, 66.80; H, 6.48.

C-(6-O-tert-Butyldiphenylsilyl-2,3-di-O-methyl-4-O-tosyl-α-d-glucopyranosyl)allene (93)

To a solution of the allene 91 (301 mg, 0.59 mmol) in dry MeOH (3 mL), K₂CO₃ (6 mg, 0.04 mmol) was added and the mixture was stirred at room temperature overnight. The residue was evaporated to afford the intermediate alcohol that was dissolved in dry pyridine (6 mL) and treated with TsCl (343 mg, 1.8 mmol) overnight. The reaction was evaporated at high vacuum rotovap, quenched with HCl 10%, and extracted with CH₂Cl₂. The organic phase was washed with a saturated aqueous solution of NaHCO₃, dried over Na₂SO₄, filtered, and evaporated. Column chromatography (hexanes–EtOAc, 9:1) gave 93 (165.1 mg, 0.27 mmol, 45%) as a colorless oil: [α]_D = +69.6 (c = 0.46, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.78–7.18 (m, 14H, Ar), 5.31 (ddd, J = 6.7, 6.7, 6.7 Hz, 1H, 1’-H), 4.82 (dd, J = 6.7, 0.0 Hz, 1H, 3’-H_b), 4.81 (dd, J = 6.9, 0.0 Hz, 1H, 3’-H_a), 4.75–4.70 (m, 2H, 1-H, 3-H), 3.88 (dd, J = 11.4, 2.2 Hz, 1H, 6-H_b), 3.82 (m, 1H, 4-H), 3.76 (dd, J = 11.0, 4.7 Hz, 1H, 6-H_a), 3.46 (s, 3H, OMe), 3.42–3.40 (m, 2H, 2-H, 5-H), 3.23 (s, 3H, OMe), 2.39 (s, 3H, OTs), 1.09 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 209.5 (C, C-2’), 144.2 (C, Ar), 135.0 (C, Ar), 133.7 (C, Ar), 133.6 (C, Ar), 127.5–135.9 (14 × CH, Ar), 85.3 (CH, C-1’), 81.7 (CH, C-2 or C-5), 80.7 (CH, C-2 or C-5), 77.9 (CH, C-1), 76.8 (CH₂, C-3’), 72.4 (CH, C-4), 70.8 (CH, C-3), 62.8 (CH₂, C-6), 60.3 (CH₃, OMe), 58.4 (CH₃, OMe), 26.8 (3 × CH₃, DPS), 21.6 (CH₃, OTs), 19.4 ppm (C, DPS). IR (CHCl₃): ν = 3015, 2933, 1955, 1599, 1373, 1112 cm^–1. MS (ESI) m/z (%) = 645 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₄H₄₂NaO₇SSi 645.2318; found 645.2321. Anal. calcd for C₃₄H₄₂O₇SSi: C, 65.56; H, 6.80. Found: C, 65.40; H, 7.05.

General Procedure for the Synthesis of the Hydroxymethyl Derivatives 48, 49, 51, 52, 58, 59, 94, 104, and 109

A solution of the allene (1 mmol) in CH₂Cl₂–MeOH (30 mL, 4:1) was cooled to −78 °C, and ozone was bubbled into the solution until it became blue. Then, nitrogen was introduced through the mixture to expel the excess of ozone, and it was heated to 0 °C. Afterward, NaBH₄ (75.3 mg, 1.99 mmol) was added slowly and the solution was stirred for 2 h at room temperature. The reaction mixture was then poured into brine, extracted with CH₂Cl₂, dried over Na₂SO₄, and concentrated. Column chromatography (hexanes–EtOAc) of the residue afforded the title alcohol.

C-(4-O-Acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-glucopyranosyl)methanol (48)

Following the general procedure starting from allene 91 (524 mg, 1.03 mmol) and purification by column chromatography (hexanes–EtOAc, 25:75), alcohol 48 (332.7 mg, 0.66 mmol, 64%) was obtained as a colorless oil: [α]_D = +19.0 (c = 0.39, CHCl₃). ¹H NMR (500 MHz CDCl₃, 2-H and 3-H are strongly coupled; therefore, 4-H and 1-H show virtual coupling effects; the chemical shifts and coupling constants shown below were obtained using DAISY) δ_H 7.70–7.65 ppm (m, 4H, Ar), 7.45–7.36 (m, 6H, Ar), 4.89 (dd, J = 8.0, 5.8 Hz, 1H, 4-H), 4.13 (ddd, J = 8.6, 4.8, 4.6 Hz, 1H, 1-H), 3.91 (dd, J = 12.0, 8.6 Hz, 1H, 1’-H_b), 3.77 (dd, J = 12.0, 4.6 Hz, 1H, 1’-H_a), 3.76 (ddd, J = 8.0, 5.8, 4.1 Hz, 1H, 5-H), 3.72 (dd, J = 10.8, 4.1 Hz, 1H, 6-H_b), 3.71 (dd, J = 10.8, 5.8 Hz, 1H, 6-H_a), 3.480 (s, 3H, OMe), 3.478 (s, 3H, OMe), 3.467 (dd, J = 7.8, 7.1 Hz, 1H, 3-H), 3.467 (dd, J = 7.1, 4.8 Hz, 1H, 2-H), 1.98 (s, 3H, OAc), 1.06 ppm (s, 9H, ^tBu), 1H from OH is missing. ¹H NMR (500 MHz, C₆D₆) δ_H 7.85–7.82 (m, 4H, Ar), 7.26–7.21 (m, 6H, Ar), 5.21 (dd, J = 8.5, 8.5 Hz, 1H, 4-H), 4.07 (ddd, J = 5.0, 5.0, 8.3 Hz, 1H, 1-H), 3.84–3.79 (m, 5H, 1’-H₂, 5-H, 6-H₂), 3.44 (dd, J = 8.4, 8.4 Hz, 1H, 3-H), 3.31 (s, 3H, OMe), 3.26 (dd, J = 8.5, 5.9 Hz, 1H, 2-H), 2.99 (s, 3H, OMe), 1.63 (s, 3H, OAc), 1.23 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 169.7 (C, OAc), 135.7 (2 × CH, Ar), 135.6 (2 × CH, Ar), 133.3 (C, Ar), 133.2 (C, Ar), 129.72 (2 × CH, Ar), 129.70 (2 × CH, Ar), 127.69 (2 × CH, Ar), 127.67 (2 × CH, Ar), 79.9 (CH, C-2 or C-5), 79.8 (CH, C-2 or C-5), 73.4 (CH, C-4), 72.5 (CH, C-1), 69.6 (CH, C-3), 63.2 (CH₂, C-6), 59.8 (CH₃, OMe), 59.6 (CH₂, C-1’), 58.9 (CH₃, OMe), 26.8 (3 × CH₃, DPS), 20.9 (CH₃, OAc), 19.2 ppm (C, DPS). IR (CHCl₃): ν = 3680, 3553, 2934, 1742, 1217 cm^–1. MS (ESI) m/z (%) = 525 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₇H₃₈NaO₇Si 525.2285; found 525.2286.

C-(6-O-tert-Butyldiphenylsilyl-2,3-di-O-methyl-4-O-tosyl-α-d-glucopyranosyl)methanol (49)

Following the general procedure starting from allene 93 (226.2 mg, 0.36 mmol) and purification by column chromatography (hexanes–EtOAc, 6:4), alcohol 49 (147.9 mg, 0.24 mmol, 67%) was obtained as a colorless oil: [α]_D = +15.2 (c = 0.54, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated coupling constants using DAISY) δ_H 7.74–7.17 (m, 14H, Ar), 4.64 (dd, J = 7.6, 6.8 Hz, 1H, 4-H), 4.04 (ddd, J = 8.5, 5.1, 4.4 Hz, 1H, 1-H), 3.834 (dd, J = 10.9, 3.7 Hz, 1H, 6-H_b), 3.831 (dd, J = 12.1, 8.5 Hz, 1H, 1’-H_b), 3.73 (ddd, J = 7.6, 6.0, 3.7 Hz, 1H, 5-H), 3.69 (dd, J = 12.1, 4.4 Hz, 1H, 1’-H_a), 3.66 (dd, J = 10.9, 6.0 Hz, 1H, 6-H_a), 3.51 (dd, J = 7.2, 6.8 Hz, 1H, 3-H), 3.47 (s, 3H, OMe), 3.43 (dd, J = 7.2, 5.1 Hz, 1H, 2-H), 3.29 (s, 3H, OMe), 2.36 (s, 3H, OTs), 1.05 ppm (s, 9H, ^tBu), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 144.5 (C, OTs), 134.3 (C, OTs), 133.3 (C, Ar), 133.2 (C, Ar), 127.6–135.6 (14 × CH, Ar), 79.8 (CH, C-2), 79.1 (CH, C-3), 76.3 (CH, C-4), 73.0 (CH, C-5), 72.2 (CH, C-1), 62.5 (CH₂, C-6), 59.8 (CH₃, OMe), 59.7 (CH₂, C-1’), 58.7 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 21.6 (CH₃, OTs), 19.2 ppm (C, DPS). IR (CHCl₃): ν = 3694, 3574, 3024, 2934, 1600, 1104 cm^–1. MS (ESI) m/z (%) = 637 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₄₂NaO₈SSi 637.2267; found 637.2257. Anal. calcd for C₃₂H₄₂O₈SSi: C, 62.51; H, 6.89; S, 5.22. Found: C, 62.29; H, 7.09; S, 4.86.

C-(4-O-Acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-galactopyranosyl)methanol (51)

Following the general procedure starting from allene 98 (461.5 mg, 0.90 mmol) and purification by column chromatography (hexanes–EtOAc, 25:75), alcohol 51 (316.3 mg, 0.63 mmol, 70%) was obtained as a colorless oil: [α]_D = +30.6 (c = 0.66, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.67–7.64 (m, 4H, Ar), 7.46–7.37 (m, 6H, Ar), 5.52 (dd, J = 3.3, 1.9 Hz, 1H, 4-H), 4.20 (ddd, J = 8.4, 6.1, 4.8 Hz, 1H, 1-H), 3.83 (ddd, J = 6.6, 6.2, 1.9 Hz, 1H, 5-H), 3.82 (dd, J = 12.0, 8.4 Hz, 1H, 1’-H_b), 3.77 (dd, J = 12.0, 5.1 Hz, 1H, 1’-H_a), 3.73 (dd, J = 10.4, 6.6 Hz, 1H, 6-H_b), 3.66 (dd, J = 9.1, 6.1 Hz, 1H, 2-H), 3.61 (dd, J = 10.4, 6.2 Hz, 1H, 6-H_a), 3.48 (s, 3H, OMe), 3.42 (dd, J = 9.1, 3.3 Hz, 1H, 3-H), 3.41 (s, 3H, OMe), 2.02 (s, 3H, OAc), 1.06 ppm (s, 9H, ^tBu), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 169.9 (C, OAc), 135.6 (4 × CH, Ar), 133.2 (C, Ar), 133.0 (C, Ar), 129.8 (2 × CH, Ar), 127.7 (4 × CH, Ar), 79.0 (CH, C-2 or C-5), 77.5 (CH, C-2 or C-5), 73.4 (CH, C-4), 71.9 (CH, C-1), 66.6 (CH, C-3), 62.2 (CH₂, C-6), 59.4 (CH₃, OMe), 59.1 (CH₂, C-1’), 57.7 (CH₃, OMe), 26.8 (3 × CH₃, DPS), 20.7 (CH₃, OAc), 19.1 ppm (C, DPS). IR (CHCl₃): ν = 3686, 3620, 3015, 2975, 1742, 1229 cm^–1. MS (ESI) m/z (%) = 525 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₇H₃₈NaO₇Si 525.2285; found 525.2284. Anal. calcd for C₂₇H₃₈O₇Si: C, 64.51; H, 7.62. Found: C, 64.20; H, 7.65.

C-(6-O-tert-Butyldiphenylsilyl-4-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-d-galactopyranosyl)methanol (52)

Following the general procedure starting from allene 99 (896.2 g, 1.28 mmol) and purification by column chromatography (hexanes–EtOAc, 6:4), alcohol 52 (567.3 mg, 0.82 mmol, 64%) was obtained as a colorless oil: [α]_D = +25.0 (c = 0.32, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.65–7.05 (m, 20H, Ar), 5.06 (ddd, J = 2.6, 1.6 Hz, ³J_PH = 8.5 Hz, 1H, 4-H), 4.09 (ddd, J = 7.3, 5.7, 5.7 Hz, 1H, 1-H), 3.80–3.68 (m, 5H, 5-H, 6-H₂, 1’-H₂), 3.57 (dd, J = 8.8, 5.6 Hz, 1H, 2-H), 3.389 (s, 3H, OMe), 3.38 (dd, J = 8.8, 2.6 Hz, 1H, 3-H), 3.35 (s, 3H, OMe), 1.93 (br s, 1H, OH), 1.03 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.8 (d, ²J_PC = 7.4 Hz, C, Ar), 150.5 (d, ²J_PC = 7.4 Hz, C, Ar), 135.6 (2 × CH, Ar), 135.5 (2 × CH, Ar), 133.3 (C, Ar), 133.2 (C, Ar), 129.74 (CH, Ar), 129.72 (CH, Ar), 129.6 (2 × CH, Ar), 129.4 (2 × CH, Ar), 127.7 (4 × CH, Ar), 125.2 (CH, Ar), 125.1 (CH, Ar), 120.33 (CH, Ar), 120.28 (CH, Ar), 120.00 (CH, Ar), 119.96 (CH, Ar), 78.9 (CH, C-3), 77.0 (CH, C-2), 74.2 (d, ²J_PC = 6.3 Hz, CH, C-4), 72.8 (d, ³J_PC = 6.3 Hz, CH, C-5), 72.6 (CH, C-1), 62.2 (CH₂, C-6), 59.58 (CH₃, OMe), 59.2 (CH₂, C-1’), 57.7 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 19.0 ppm (C, DPS). IR (CHCl₃): ν = 3690, 3546, 3023, 2934, 1592, 1206 cm^–1. MS (ESI) m/z (%) = 715 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₇H₄₅NaO₉PSi 715.2468; found 715.2475. Anal. calcd for C₃₇H₄₅O₉PSi: C, 64.14; H, 6.55. Found: C, 64.02; H, 6.67.

C-(4-O-Acetyl-2,3-di-O-methyl-α-d-fucopyranosyl)methanol (58)

Alcohol 109 (200 mg, 0.68 mmol) was dissolved in dry DMF (2.7 mL), and DPSCl (238 μL, 1.01 mmol) and imidazole (138 mg, 2.03 mmol) were added at room temperature. After 3 h, the reaction was evaporated in a high vacuum rotovap, quenched with H₂O, and extracted with CH₂Cl₂. The organic phase was dried over Na₂SO₄, filtered, and evaporated. To a solution of the resulting crude in dry EtOAc (16 mL) was added Pd/C 10% (152 mg), and the mixture was submitted to H₂ atmosphere overnight. The reaction was filtered over a pad of Celite and evaporated. The alcohol was protected by treatment with dry pyridine (2.6 mL), Ac₂O (0.9 mL), and DMAP (8.3 mg, 0.068 mmol) for 0.5 h. The mixture was evaporated in a high vacuum rotovap, quenched with aqueous HCl 10%, and extracted with CH₂Cl₂. The organic phase was washed with a saturated aqueous solution of NaHCO₃, dried with Na₂SO₄, filtered, and concentrated to dryness. Finally, the silyl group was deprotected by treatment with a 1 M solution of TBAF/THF (1.4 mL, 1.4 mmol) in dry THF (13.6 mL) for 4 h at room temperature. The mixture was evaporated, and the residue was chromatographed in a silica gel column (hexanes–EtOAc, 4:6 to 2:8) to give 58 (111 mg, 0.45 mmol, 66%) as a colorless oil: [α]_D = −76.0 (c = 0.65, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 5.33 (dd, J = 3.5, 2.0 Hz, 1H, 4-H), 4.23 (ddd, J = 8.0, 5.9, 4.7 Hz, 1H, 1-H), 3.96 (dddd, J = 6.5, 6.5, 6.5, 2.0 Hz, 1H, 5-H), 3.89 (dd, J = 12.1, 8.0 Hz, 1H, 1’-H_b), 3.85 (dd, J = 12.1, 4.7 Hz, 1H, 1’-H_a), 3.71 (dd, J = 8.2, 5.9 Hz, 1H, 2-H), 3.50 (dd, J = 8.2, 3.5 Hz, 1H, 3-H), 3.50 (s, 3H, OMe), 3.42 (s, 3H, OMe), 2.17 (s, 3H, OAc), 2.10 (br s, 1H, OH), 1.17 ppm (d, J = 6.5 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.6 (C, OAc), 78.7 (CH, C-3), 77.1 (CH, C-2), 73.4 (CH, C-1), 69.5 (CH, C-4), 67.0 (CH, C-5), 59.5 (CH₂, C-1’), 59.3 (CH₃, OMe), 57.5 (CH₃, OMe), 20.8 (CH₃, OAc), 16.5 ppm (CH₃, C-6). IR (CHCl₃): ν = 3677, 3502, 3018, 2939, 1739, 1239 cm^–1. MS (ESI) m/z (%) = 271 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₁H₂₀NaO₆ 271.1158; found 271.1159.

C-(4-O-Diphenoxyphosphoryl-2,3-di-O-methyl-α-d-fucopyranosyl)methanol (59)

Alcohol 109 (1.4 g, 4.73 mmol) was dissolved in dry DMF (18.9 mL), and imidazole (960 mg, 14.1 mmol) and DPSCl (1.7 mL, 7.25 mmol) were added at room temperature. After 3 h, the reaction was evaporated in a high vacuum rotovap, quenched with H₂O, and extracted with CH₂Cl₂. The organic phase was dried over Na₂SO₄, filtered, and evaporated. To a solution of the resulting crude in dry EtOAc (111 mL) was added Pd/C 10% (1.06 g), and the mixture was submitted to a H₂ atmosphere overnight. The reaction was filtered over a pad of Celite and evaporated. The alcohol was protected without purification by treatment with DMAP (2.66 g, 21.7 mmol) and ClPO(OPh)₂ (2.82 mL, 21.7 mmol) in dry CH₂Cl₂ (110 mL) for 3.5 h. The mixture was quenched with a saturated aqueous NH₄Cl solution and extracted with CH₂Cl₂. The organic phase was dried with Na₂SO₄, filtered, and concentrated to dryness. Finally, the silyl group was deprotected by treatment with a 1 M solution of TBAF/THF (9.46 mL, 9.46 mmol) in dry THF (95 mL) for 3.5 h at room temperature. The mixture was evaporated, and the residue was chromatographed on a silica gel column (hexanes–EtOAc, 1:1) to give 59 (1.24 g, 2.84 mmol, 60%) as a colorless oil: [α]_D = −41.8 (c = 0.49, CHCl₃). ¹H NMR (400 MHz, CDCl₃, simulated coupling constants using DAISY) δ_H 7.37–7.17 (m, 10H, Ar), 4.92 (ddd, J = 3.0, 2.5 Hz, ³J_PH = 9.1 Hz, 1H, 4-H), 4.14 (ddd, J = 7.5, 5.7, 5.2 Hz, 1H, 1-H), 3.96 (ddddd, J = 6.5, 6.5, 6.5, 2.5 Hz, ⁴J_PH = 1.9 Hz, 1H, 5-H), 3.87–3.77 (m, 2H, 1’-H₂), 3.60 (dd, J = 8.4, 5.2 Hz, 1H, 2-H), 3.53 (ddd, J = 8.4, 3.0, Hz, ⁴J_PH = 1.0 Hz, 1H, 3-H), 3.43 (s, 3H, OMe), 3.41 (s, 3H, OMe), 1.22 ppm (d, J = 6.5 Hz, 3H, 6-H₃), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 150.8 (d, ²J_PC = 8.5 Hz, C, Ar), 150.6 (d, ²J_PC = 7.4 Hz, C, Ar), 129.7 (2 × CH, Ar), 129.3 (2 × CH, Ar), 125.3 (CH, Ar), 125.1 (CH, Ar), 120.32 (CH, Ar), 120.28 (CH, Ar), 120.11 (CH, Ar), 120.07 (CH, Ar), 78.7 (CH, C-3), 76.9 (CH, C-2), 76.8 (d, ³J_PC = 6.3 Hz, CH, C-4), 72.3 (CH, C-1), 67.9 (d, ³J_PC = 5.3 Hz, CH, C-5), 60.1 (CH₂, C-1’), 59.5 (CH₃, OMe), 57.8 (CH₃, OMe), 15.9 ppm (CH₃, C-6). IR (CHCl₃): ν = 3694, 3018, 2938, 1490, 1218 cm^–1. MS (ESI) m/z (%) = 461 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₁H₂₇NaO₈P 461.1341; found 461.1342. Anal. calcd for C₂₁H₂₇O₈P: C, 57.53; H, 6.21. Found: C, 57.62; H, 6.49.

C-(6-O-tert-Butyldiphenylsilyl-4-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-d-glucopyranosyl)methanol (94)

Following the general procedure starting from allene 92 (1.08 g, 1.54 mmol) and purification by column chromatography (hexanes–EtOAc, 6:4), alcohol 94 (556.2 mg, 0.80 mmol, 52%) was obtained as a colorless oil: [α]_D = +30.3 (c = 0.33, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated coupling constants using DAISY) δ_H 7.65–7.07 (m, 20H, Ar), 4.56 (ddd, J = 8.5, 7.6 Hz, ³J_PH = 9.4 Hz, 1H, 4-H), 4.13 (ddd, J = 8.8, 5.7, 4.6 Hz, 1H, 1-H), 3.91 (dd, J = 11.0, 32.8 Hz, 1H, 6-H_b), 3.90 (dd, J = 12.1, 8.8 Hz, 1H, 1’-H_b), 3.83 (ddd, J = 8.5, 5.9, 2.8 Hz, 1H, 5-H), 3.76 (dd, J = 11.0, 5.9 Hz, 1H, 6-H_a), 3.75 (dd, J = 12.1, 4.6 Hz, 1H, 1’-H_a), 3.57 (dd, J = 7.9, 7.6 Hz, 1H, 3-H), 3.50 (dd, J = 7.9, 5.7 Hz, 1H, 2-H), 3.45 (s, 3H, OMe), 3.42 (s, 3H, OMe), 1.03 ppm (s, 9H, ^tBu), 1H from OH is missing. ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 150.7 (d, ²J_PC = 7.0 Hz, C, Ar), 150.5 (d, ²J_PC = 7.1 Hz, C, Ar), 133.3 (2 × C, Ar), 120.0–135.7 (20 × CH, Ar), 80.6 (CH, C-2 or C-3), 80.4 (CH, C-2 or C-3), 75.7 (d, ²J_PC = 6.3 Hz, CH, C-4), 73.3 (d, ³J_PC = 6.3 Hz, CH, C-5), 72.6 (CH, C-1), 62.9 (CH₂, C-6), 59.9 (CH₃, OMe), 59.3 (CH₂, C-1’), 58.8 (CH₃, OMe), 26.8 (3 × CH₃, DPS), 19.2 ppm (C, DPS). IR (CHCl₃): ν = 3676, 3532, 3016, 2934, 1591, 1490 cm^–1. MS (ESI) m/z (%) = 715 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₇H₄₅NaO₉PSi 715.2468; found 715.2469. Anal. calcd for C₃₇H₄₅O₉PSi: C, 64.14; H, 6.55. Found: C, 64.06; H, 6.36.

C-(4-O-Benzyl-2,3-di-O-methyl-α-l-rhamnopyranosyl)methanol (104)

Allene 103 (154 mg, 0.49 mmol) in TFA/H₂O (4.5 mL, 4:6) was stirred at room temperature for 2 h. The solution was evaporated in a high vacuum rotovap, poured over a saturated aqueous solution of NaHCO₃, extracted with CH₂Cl₂, dried over Na₂SO₄, and concentrated. The crude was dissolved in dry DMF (5.9 mL) under a N₂ atmosphere, and NaH 60% in mineral oil (58.8 mg, 1.47 mmol) was slowly added at 0 °C. After 20 min, MeI (122 μL, 1.96 mmol) was dropwise added and stirring was continued at 0 °C for 1 h. Ice-water was used to destroy the excess of NaH, and the mixture was evaporated in a high vacuum rotovap, poured over a saturated solution of NH₄Cl, and extracted with CH₂Cl₂. The combined organic extracts were dried over Na₂SO₄ and concentrated to dryness under reduced pressure. The organic residue was then submitted to the general procedure for the synthesis of hydroxymethyl derivatives. Column chromatography of the residue (hexanes–EtOAc, 4:6) gave 104 (65.4 mg, 0.22 mmol, 45%, three steps) as a colorless oil: [α]_D = −22.4 (c = 0.293, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.37–7.29 (m, 5H, Ar), 4.70 (d, J = 11.7 Hz, 1H, OBn), 4.65 (d, J = 11.7 Hz, 1H, OBn), 3.99 (m, 1H, 1-H), 3.89 (dddd, J = 6.6, 6.6, 6.6, 4.7 Hz, 1H, 5-H), 3.80 (dd, J = 11.7, 7.0 Hz, 1H, 1’-H_b), 3.70 (dd, J = 11.4, 4.5 Hz, 1H, 1’-H_a), 3.60–3.56 (m, 2H, 2-H, 3-H), 3.52 (dd, J = 5.4, 4.7 Hz, 1H, 4-H), 3.45 (s, 3H, OMe), 3.44 (s, 3H, OMe), 2.07 (br s, 1H, OH), 1.34 ppm (d, J = 7.0 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 138.2 (C, Ar), 128.4 (2 × CH, Ar), 127.8 (3 × CH, Ar), 78.4 (CH, C-2 or C-3), 78.0 (CH, C-4), 75.7 (CH, C-2 or C-3), 73.4 (CH₂, OBn), 70.7 (CH, C-1), 70.6 (CH, C-5), 61.7 (CH₂, C-1’), 58.0 (CH₃, OMe), 57.4 (CH₃, OMe), 17.2 ppm (CH₃, C-6). IR (CHCl₃): ν = 3587, 3478, 2587, 2478, 2015, 2935, 1455, 1088 cm^–1. MS (ESI) m/z (%) = 319 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₆H₂₄NaO₅ 319.1521; found 319.1525. Anal. calcd for C₁₆H₂₄O₅: C, 64.84; H, 8.16. Found: C, 64.61; H, 8.37.

C-(4-O-Benzyl-2,3-di-O-methyl-α-d-fucopyranosyl)methanol (109)

Alcohol 108 (251.4 mg, 0.84 mmol) was dissolved in dry DMF (10 mL) under a N₂ atmosphere, and NaH 60% in mineral oil (50.4 mg, 1.26 mmol) was slowly added at 0 °C. After 20 min, BnBr (200 μL, 1.68 mmol) was dropwise added and stirring was continued at 0 °C for 2 h. Ice-water was used to destroy the NaH in excess, and the mixture was evaporated in a high vacuum rotovap, poured over a saturated solution of NH₄Cl, and extracted with CH₂Cl₂. The combined extracts were dried over Na₂SO₄ and concentrated to dryness under reduced pressure. The crude was dissolved in TFA/H₂O (7.7 mL, 4:6) and stirred at 40 °C overnight. The solution was evaporated in a high vacuum rotovap, quenched with a saturated aqueous solution of NaHCO₃, and extracted with CH₂Cl₂. The organic residue was submitted to methyl protection by treatment with NaH 60% (100.8 mg, 2.52 mmol) and MeI (209 μL, 3.36 mmol) in DMF (10 mL) for 2 h from 0 °C until room temperature. Ice-water was used to destroy the excess of NaH, and the mixture was evaporated in a high vacuum rotovap, poured over a saturated solution of NH₄Cl, and extracted with CH₂Cl₂. The organic phase was dried over Na₂SO₄ and concentrated to dryness under reduced pressure. Finally, the crude was submitted to the general procedure to give hydroxymethyl derivatives. Column chromatography of the residue (hexanes–EtOAc, 4:6) gave 109 (106.6 mg, 0.36 mmol, 43%) as a colorless oil: [α]_D = −30.2 (c = 1.35, CHCl₃). ¹H NMR (400 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.39–7.27 (m, 5H, Ar), 4.77 (d, J = 11.8 Hz, 1H, OBn), 4.63 (d, J = 11.8 Hz, 1H, OBn), 4.13 (ddd, J = 7.9, 4.7, 4.2 Hz, 1H, 1-H), 3.97 (dddd, J = 6.7, 6.7, 6.7, 3.6 Hz, 1H, 5-H), 3.83 (dd, J = 11.6, 7.9 Hz, 1H, 1’-H_b), 3.76 (dd, J = 3.6, 2.9 Hz, 1H, 4-H), 3.74 (dd, J = 11.6, 4.7 Hz, 1H, 1’-Ha), 3.69 (dd, J = 7.0, 4.2 Hz, 1H, 2-H), 3.53 (dd, J = 7.0, 2.9 Hz, 1H, 3-H), 3.50 (s, 3H, OMe), 3.45 (s, 3H, OMe), 2.11 (br s, 1H, OH), 1.28 ppm (d, J = 6.7 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 138.4 (C, Ar), 128.3 (2 × CH, Ar), 128.0 (2 × CH, Ar), 127.7 (CH, Ar), 79.4 (CH, C-3), 78.1 (CH, C-2), 75.0 (CH, C-4), 73.4 (CH₂, OBn), 70.7 (CH, C-1), 69.4 (CH, C-5), 60.8 (CH₂, C-1’), 58.9 (CH₃, OMe), 58.6 (CH₃, OMe), 15.5 ppm (CH₃, C-6). IR (CHCl₃): ν = 3676, 3588, 3012, 2937, 1101 cm^–1. MS (ESI) m/z (%) = 319 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₆H₂₄NaO₅ 319.1521; found 319.1519. Anal. calcd for C₁₆H₂₄O₅: C, 64.84; H, 8.16; found: C, 64.89; H, 8.20.

General Procedure for the Synthesis of Phthalimide Derivatives 16, 17, 18, 19, 20, 21, 22, 23, 24, and 105

DEAD (394 μL, 2.50 mmol) was added dropwise to a stirred solution of the alcohol (1 mmol), N-hydroxyphthalimide (408 mg, 2.5 mmol), and PPh₃ (656 mg, 2.5 mmol) in dry THF (10 mL), and the resulting solution was stirred at 0 °C for 0.5–2.5 h. Then, the solvent was removed and the crude was quenched with water and extracted with CHCl₃. The combined organic extracts were dried over Na₂SO₄ and concentrated under reduced pressure. Column chromatography of the residue (hexanes–EtOAc) gave the corresponding phthalimides.

C-(4-O-Acetyl-6-O-tert-Butyldiphenylsilyl-2,3-di-O-methyl-α-d-glucopyranosyl)N-methoxyphthalimide (16)

Following the general procedure starting from alcohol 48 (332 mg, 0.66 mmol) and purification by column chromatography (hexanes–EtOAc, 8:2), product 16 (281 mg, 0.43 mmol, 66%) was obtained as an amorphous solid: [α]_D = +10.4 (c = 0.53, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated coupling constants using DAISY) δ_H 7.74–7.62 (m, 8H, Ar), 7.43–7.34 (m, 6H, Ar), 5.17 (dd, J = 6.8, 6.5 Hz, 1H, 4-H), 4.58 (dd, J = 10.8, 7.5 Hz, 1H, 1’-H_b), 4.48 (ddd, J = 7.5, 4.6, 3.9 Hz, 1H, 1-H), 4.37 (dd, J = 10.8, 3.9 Hz, 1H, 1’-H_a), 3.88 (ddd, J = 6.8, 5.0, 4.6 Hz, 1H, 5-H), 3.77 (dd, J = 11.0, 4.6 Hz, 1H, 6-H_b), 3.71 (dd, J = 11.0, 5.0 Hz, 1H, 6-H_a), 3.52 (dd, J = 7.1, 4.6 Hz, 1H, 2-H), 3.51 (s, 3H, OMe), 3.49 (s, 3H, OMe), 3.46 (dd, J = 7.1, 6.5 Hz, 1H, 3-H), 2.03 (s, 3H, OAc), 1.03 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 169.7 (C, OAc), 163.1 (2 × C, CO), 135.64 (2 × CH, Ar), 135.60 (2 × CH, Ar), 134.3 (2 × CH, Ar), 133.4 (C, Ar), 133.3 (C, Ar), 129.5 (CH, Ar), 129.4 (CH, Ar), 128.8 (2 × C, Ar), 127.5 (4 × CH, Ar), 123.4 (2 × CH, Ar), 78.3 (CH, C-2 or C-3), 78.0 (CH, C-2 or C-3), 74.5 (CH₂, C-1’), 73.6 (CH, C-5), 70.3 (CH, C-1), 68.2 (CH, C-4), 62.3 (CH₂, C-6), 59.3 (CH₃, OMe), 58.7 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 21.0 (CH₃, OAc), 19.1 ppm (C, DPS). IR (CHCl₃): ν = 2934, 1792, 1735, 1236 cm^–1. MS (ESI) m/z (%) = 670 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₅H₄₁NNaO₉Si 670.2448; found 670.2441. Anal. calcd for C₃₅H₄₁NO₉Si: C, 64.89; H, 6.38; N, 2.16. Found: C, 65.05; H, 6.40; N, 2.18.

C-(6-O-tert-Butyldiphenylsilyl-4-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-d-glucopyranosyl)N-methoxyphthalimide (17)

Following the general procedure starting from alcohol 94 (507.2 mg, 0.73 mmol) and purification by column chromatography (hexanes–EtOAc, 75:25), product 17 (331.3 mg, 0.40 mmol, 54%) was obtained as a an amorphous solid: [α]_D = +14.9 (c = 0.47, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated coupling constants using DAISY) δ_H 7.73–7.11 (m, 24H, Ar), 4.87 (ddd, J = 7.0, 7.0 Hz, ³J_PH = 9.4 Hz, 1H, 4-H), 4.58 (dd, J = 10.9, 7.6 Hz, 1H, 1’-H_b), 4.48 (ddd, J = 7.6, 5.3, 3.6 Hz, 1H, 1-H), 4.36 (dd, J = 10.9, 3.6 Hz, 1H, 1’-H_a), 3.95 (ddd, J = 7.0, 4.0, 4.0 Hz, 1H, 5-H), 3.77 (dd, J = 4.0, 4.0 Hz, 2H, 6-H₂), 3.60 (dd, J = 7.4, 7.0 Hz, 1H, 3-H), 3.51 (dd, J = 7.4, 5.3 Hz, 1H, 2-H), 3.48 (s, 3H, OMe), 3.44 (s, 3H, OMe), 1.00 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 163.2 (2 × C, CO), 150.7 (d, ²J_PC = 7.0 Hz, C, Ar), 150.6 (d, ²J_PC = 7.8 Hz, C, Ar), 133.5 (C, Ar), 133.4 (C, Ar), 128.8 (2 × C, Ar), 119.9–135.7 (24 × CH, Ar), 79.3 (CH, C-3), 78.8 (CH, C-2), 74.5 (d, ²J_PC = 7.0 Hz, CH, C-4), 74.0 (CH₂, C-1’), 73.7 (d, ³J_PC = 7.1 Hz, CH, C-5), 70.6 (CH, C-1), 62.1 (CH₂, C-6), 59.6 (CH₃, OMe), 58.7 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 19.2 ppm (C, DPS). IR (CHCl₃): ν = 2934, 1792, 1735, 1490, 1190 cm^–1. MS (ESI) m/z (%) = 860 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₅H₄₈NNaO₁₁PSi 860.2632; found 860.2628. Anal. calcd for C₄₅H₄₈NO₁₁PSi: C, 64.50; H, 5.77; N, 1.67. Found: C, 64.42; H, 5.61; N, 1.82.

C-(6-O-tert-Butyldiphenylsilyl-2,3-di-O-methyl-4-O-tosyl-α-d-glucopyranosyl)N-methoxyphthalimide (18)

Following the general procedure starting from alcohol 49 (124.5 mg, 0.20 mmol) and purification by column chromatography (hexanes–EtOAc, 75:25), phthalimide 18 (121.5 mg, 0.16 mmol, 80%) was obtained as a colorless oil: [α]_D = +5.8 (c = 0.36, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.78–7.13 (m, 18H, Ar), 4.96 (dd, J = 6.2, 5.8 Hz, 1H, 4-H), 4.50 (dd, J = 11.0, 7.4 Hz, 1H, 1’-H_b), 4.39 (ddd, J = 7.4, 4.3, 3.8 Hz, 1H, 1-H), 4.32 (dd, J = 11.0, 3.8 Hz, 1H, 1’-H_a), 3.86–3.80 (m, 2H, 5-H, 6-H_b), 3.71 (m, 1H, 6-H_a), 3.60 (dd, J = 6.4, 5.8 Hz, 1H, 3-H), 3.51 (s, 3H, OMe), 3.48 (dd, J = 6.4, 4.3 Hz, 1H, 2-H), 3.36 (s, 3H, OMe), 2.35 (s, 3H, OTs), 1.05 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 163.1 (2 × C, CO), 144.3 (C, OTs), 134.3 (C, OTs), 133.5 (C, Ar), 133.2 (C, Ar), 128.7 (2 × C, Ar), 123.4–135.6 (18 × CH, Ar), 77.8 (CH, C-2), 77.6 (CH, C-3), 74.8 (CH₂, C-1’), 74.7 (CH, C-4), 73.5 (CH, C-5), 69.9 (CH, C-1), 61.7 (CH₂, C-6), 59.3 (CH₃, OMe), 58.5 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 21.5 (CH₃, OTs), 19.2 ppm (C, DPS). IR (CHCl₃): ν = 3024, 2934, 1792, 1735, 1215, 1106 cm^–1. MS (ESI) m/z (%) = 782 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₀H₄₅NNaO₁₀SSi 782.2431; found 782.2434. Anal. calcd for C₄₀H₄₅NO₁₀SSi: C, 63.22; H, 5.97; N, 1.84; S, 4.22. Found: C, 63.35; H, 6.17; N, 1.75; S, 4.43.

C-(4,6-Bis-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-d-glucopyranosyl)N-methoxyphthalimide (19)

Following the general procedure starting from alcohol 95 (315 mg, 0.46 mmol) and purification by column chromatography (hexanes–EtOAc, 1:1), product 19 (235.8 mg, 0.28 mmol, 62%) was obtained as a colorless oil: [α]_D = +13.5 (c = 1.90, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.83–7.81 (m, 2H, Ar), 7.74–7.73 (m, 2H, Ar), 7.33–7.11 (m, 20H, Ar), 4.53 (ddd, J = 7.9, 7.9 Hz, ³J_PH = 7.9 Hz, 1H, 4-H), 4.49 (dd, J = 10.1, 6.6 Hz, 1H, 1’-H_b), 4.42–4.33 (m, 3H, 1-H, 6-H_b, 1’-H_a), 4.26 (ddd, J = 12.3, 4.7 Hz, ³J_PH = 7.9 Hz, 1H, 6-H_a), 4.14 (m, 1H, 5-H), 3.58 (dd, J = 7.3, 7.3 Hz, 1H, 3-H), 3.44 (s, 3H, OMe), 3.43 (s, 3H, OMe), 3.41 ppm (dd, J = 7.6, 4.7 Hz, 1H, 2-H). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.3 (2 × C, CO), 150.6 (d, ²J_PC = 6.3 Hz, 2 × C, Ar), 150.5 (d, ²J_PC = 7.4 Hz, C, Ar), 150.4 (d, ²J_PC = 8.5 Hz, C, Ar), 128.8 (2 × C, Ar), 120.0–134.5 (24 × CH, Ar), 79.3 (CH, C-3), 78.4 (CH, C-2), 74.4 (d, ²J_PC = 6.4 Hz, CH, C-4), 74.1 (CH₂, C-1’), 72.8 (dd, ³J_PC = 6.1, 6.1 Hz, CH, C-5), 70.4 (CH, C-1), 66.5 (d, ²J_PC = 6.3 Hz, CH₂, C-6), 59.8 (CH₃, OMe), 58.8 ppm (CH₃, OMe). IR (CHCl₃): ν = 3018, 2937, 1736, 1214 cm^–1. MS (ESI) m/z (%) = 854 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₁H₃₉NNaO₁₄P₂: 854.1744; found 854.1743. Anal. calcd for C₄₁H₃₉NO₁₄P₂: C, 59.21; H, 4.73; N, 1.68. Found: C, 58.99; H, 4.89; N, 2.08.

C-(4-O-Acetyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-galactopyranosyl)N-methoxyphthalimide (20)

Following the general procedure starting from alcohol 51 (285.9 mg, 0.57 mmol) and purification by column chromatography (hexanes–EtOAc, 75:25), product 20 (318.2 mg, 0.49 mmol, 86%) was obtained as a crystalline solid: mp 48.9–50.0 °C (n-hexane–EtOAc); [α]_D = +6.7 (c = 0.43, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.74–7.61 (m, 8H, Ar), 7.43–7.35 (m, 6H, Ar), 5.68 (dd, J = 3.2, 2.1 Hz, 1H, 4-H), 4.62–4.58 (m, 2H, 1-H, 1’-H_b), 4.38 (m, 1H, 1’-H_a), 4.09 (ddd, J = 8.1, 5.7, 2.1 Hz, 1H, 5-H), 3.69 (dd, J = 9.1, 5.4 Hz, 1H, 2-H), 3.64 (dd, J = 10.0, 5.7 Hz, 1H, 6-H_b), 3.54 (dd, J = 10.0, 8.1 Hz, 1H, 6-H_a), 3.50 (s, 3H, OMe), 3.46 (dd, J = 9.1, 3.2 Hz, 1H, 3-H), 3.44 (s, 3H, OMe), 2.02 (s, 3H, OAc), 1.03 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 169.7 (C, OAc), 163.2 (2 × C, CO), 135.60 (2 × CH, Ar), 135.56 (2 × CH, Ar), 134.4 (2 × CH, Ar), 133.3 (C, Ar), 133.1 (C, Ar), 129.7 (CH, Ar), 129.6 (CH, Ar), 128.8 (2 × C, Ar), 127.67 (2 × CH, Ar), 127.66 (2 × CH, Ar), 123.4 (2 × CH, Ar), 78.9 (CH, C-3), 76.3 (CH, C-2), 72.8 (CH₂, C-1’), 72.2 (CH, C-1), 71.5 (CH, C-5), 66.1 (CH, C-4), 61.1 (CH₂, C-6), 59.3 (CH₃, OMe), 57.7 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 20.8 (CH₃, OAc), 19.0 ppm (C, DPS). IR (CHCl₃): ν = 2933, 1792, 1734, 1226 cm^–1. MS (ESI) m/z (%) = 670 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₅H₄₁NNaO₉Si: 670.2448; found 670.2443. Anal. calcd for C₃₅H₄₁NO₉Si: C, 64.89; H, 6.38; N, 2.16. Found: C, 64.67; H, 6.41; N, 2.23.

C-(6-O-tert-Butyldiphenylsilyl-4-O-diphenoxyphosphoryl-2,3-di-O-methyl-α-d-galactopyranosyl)N-methoxyphthalimide (21)

Following the general procedure starting from alcohol 52 (510 mg, 0.74 mmol) (327 mg, 0.51 mmol) and purification by column chromatography (hexanes–EtOAc, 8:2), product 21 (574 mg, 0.68 mmol, 93%) was obtained as a colorless oil: [α]_D = −9.1 (c = 0.67, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.74–7.11 (m, 24H, Ar), 5.24 (ddd, J = 2.9, 2.7 Hz, ³J_PH = 8.7 Hz, 1H, 4-H), 4.47–4.41 (m, 2H, 1-H, 1’-H_b), 4.33 (m, 1H, 1’-H_a), 4.03 (dddd, J = 6.7, 5.8, 2.7 Hz, ⁴J_PH = 2.3 Hz, 1H, 5-H), 3.77 (dd, J = 10.6, 5.8 Hz, 1H, 6-H_b), 3.74 (dd, J = 10.6, 6.7 Hz, 1H, 6-H_a), 3.66 (dd, J = 8.2, 5.6 Hz, 1H, 2-H), 3.42 (s, 3H, OMe), 3.39 (dd, J = 8.2, 2.9 Hz, 1H, 3-H), 3.35 (s, 3H, OMe), 1.00 ppm (s, 9H, ^tBu). ¹³C{¹H} NMR (100.6 MHz, CDCl₃) δ_C 163.2 (2 × C, CO), 150.7 (d, ²J_PC = 7.4 Hz, C, Ar), 150.6 (d, ²J_PC = 6.4 Hz, C, Ar), 135.58 (2 × CH, Ar), 135.55 (2 × CH, Ar), 134.4 (2 × CH, Ar), 133.5 (C, Ar), 133.3 (C, Ar), 129.7 (2 × CH, Ar), 129.6 (CH, Ar), 129.5 (CH, Ar), 129.4 (2 × CH, Ar), 128.8 (2 × C, Ar), 127.7 (2 × CH, Ar), 127.6 (2 × CH, Ar), 125.1 (CH, Ar), 125.0 (CH, Ar), 123.4 (2 × CH, Ar), 120.4 (CH, Ar), 120.3 (CH, Ar), 120.1 (CH, Ar), 120.0 (CH, Ar), 78.3 (CH, C-3), 75.7 (CH, C-2), 73.8 (d, ²J_PC = 6.3 Hz, CH, C-4), 73.5 (CH₂, C-1’), 73.1 (CH, C-1), 70.6 (br s, CH, C-5), 60.9 (CH₂, C-6), 59.5 (CH₃, OMe), 57.8 (CH₃, OMe), 26.7 (3 × CH₃, DPS), 19.1 ppm (C, DPS). IR (CHCl₃): ν = 3015, 2933, 1792, 1730, 1490, 1190 cm^–1. MS (ESI) m/z (%) = 860 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₄₅H₄₈NNaO₁₁PSi: 860.2632; found 860.2648. Anal. calcd for C₄₅H₄₈NO₁₁PSi: C, 64.50; H, 5.77; N, 1.67. Found: C, 64.82; H, 6.01; N, 1.92.

C-(4-O-Diphenoxyphosphoryl-2,3-di-O-methyl-α-l-rhamnopyranosyl)N-methoxyphthalimide (22)

Alcohol 105 (231.7 mg, 0.66 mmol) in dry CH₂Cl₂ (38 mL) was treated with DMAP (371 mg, 3.04 mmol) and ClPO(OPh)₂ (0.63 mL, 3.04 mmol) for 2 h. The reaction was quenched with a saturated aqueous solution of NH₄Cl and extracted with CH₂Cl₂. The organic phase was dried over Na₂SO₄, filtered, and evaporated. Column chromatography of the residue (hexanes–EtOAc, 6:4) gave the compound 22 (333 mg, 0.55 mmol, 84%) as an amorphous solid: [α]_D = −0.1 (c = 0.41, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.84–7.82 (m, 2H, Ar), 7.75–7.73 (m, 2H, Ar), 7.37–7.17 (m, 10H, Ar), 4.63 (ddd, J = 5.2, 3.2 Hz, ³J_PH = 9.2 Hz, 1H, 4-H), 4.46 (dd, J = 10.9, 3.2 Hz, 1H, 1’-H_b), 4.38 (dd, J = 10.9, 6.2 Hz, 1H, 1’-H_a), 4.23 (ddd, J = 7.6, 6.2, 3.2 Hz, 1H, 1-H), 4.01 (dddd, J = 6.9, 6.9, 6.9, 3.7 Hz, 1H, 5-H), 3.71 (dd, J = 5.2, 3.2 Hz, 1H, 3-H), 3.61 (dd, J = 7.6, 3.2 Hz, 1H, 2-H), 3.42 (s, 3H, OMe), 3.35 (s, 3H, OMe), 1.34 ppm (d, J = 6.9 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.2 (2 × C, CO), 150.5 (d, ²J_PC = 7.4 Hz, C, Ar), 150.3 (d, ²J_PC = 7.4 Hz, C, Ar), 134.4 (2 × CH, Ar), 129.8 (2 × CH, Ar), 129.7 (2 × CH, Ar), 128.9 (2 × C, Ar), 125.42 (CH, Ar), 125.37 (CH, Ar), 123.4 (2 × CH, Ar), 120.2 (CH, Ar), 120.12 (CH, Ar), 120.11 (CH, Ar), 120.07 (CH, Ar), 77.4 (d, ²J_PC = 6.4 Hz, CH, C-4), 77.2 (CH₂, C-1’), 76.2 (d, ³J_PC = 3.2 Hz, CH, C-3), 73.9 (CH, C-2), 71.6 (d, ³J_PC = 5.3 Hz, CH, C-5), 68.2 (CH, C-1), 58.3 (CH₃, OMe), 57.2 (CH₃, OMe), 16.2 ppm (CH₃, C-6). IR (CHCl₃): ν = 3015, 2939, 1792, 1736, 1490, 1209 cm^–1. MS (ESI) m/z (%) = 606 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₉H₃₀NNaO₁₀P: 606.1505; found 606.1516. Anal. calcd for C₂₉H₃₀NO₁₀P: C, 59.69; H, 5.18; N, 2.40. Found: C, 59.37; H, 5.40; N, 2.68.

C-(4-O-Acetyl-2,3-di-O-methyl-α-l-fucopyranosyl)N-methoxyphthalimide (23)

Following the general procedure starting from 58 (65.6 mg, 0.26 mmol) and purification by column chromatography (hexanes–Et₂O, 4:6), product 23 (52.4 mg, 0.13 mmol, 51%) was obtained as a white crystalline solid: mp 37.8–38.5 °C (n-hexane–EtOAc). [α]_D = −42.5 (c = 0.72, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.86–7.84 (m, 2H, Ar), 7.78–7.76 (m, 2H, Ar), 5.31 (dd, J = 3.4, 2.0 Hz, 1H, 4-H), 4.67 (ddd, J = 9.0, 5.9, 1.9 Hz, 1H, 1-H), 4.63 (dd, J = 10.7, 9.0 Hz, 1H, 1’-H_b), 4.39 (dd, J = 10.7, 1.9 Hz, 1H, 1’-H_a), 4.09 (dddd, J = 6.4, 6.4, 6.4, 2.0 Hz, 1H, 5-H), 3.71 (dd, J = 9.3, 5.9 Hz, 1H, 2-H), 3.51 (s, 3H, OMe), 3.40 (s, 3H, OMe), 3.36 (dd, J = 9.3, 3.4 Hz, 1H, 3-H), 2.16 (s, 3H, OAc), 1.11 ppm (d, J = 6.4 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 170.6 (C, OAc), 163.3 (2 × C, CO), 134.5 (2 × CH, Ar), 128.8 (2 × C, Ar), 123.5 (2 × CH, Ar), 78.6 (CH, C-3), 76.1 (CH, C-2), 72.8 (CH₂, C-1’), 71.8 (CH, C-1), 69.4 (CH, C-4), 67.0 (CH, C-5), 59.2 (CH₃, OMe), 57.6 (CH₃, OMe), 20.8 (CH₃, OAc), 16.1 ppm (CH₃, C-6). IR (CHCl₃): ν = 3018, 2936, 1791, 1744, 1239 cm^–1. MS (ESI) m/z (%) = 416 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₉H₂₃NNaO₈: 416.1321; found 416.1328. Anal. calcd for C₁₉H₂₃NO₈: C, 58.01; H, 5.89; N, 3.56. Found: C, 58.33; H, 5.95; N, 3.83.

C-(4-O-Diphenoxyphosphoryl-2,3-di-O-methyl-α-l-fucopyranosyl)N-methoxyphthalimide (24)

Following the general procedure starting from 59 (232 mg, 0.53 mmol) and purification by column chromatography (hexanes–EtOAc, 6:4), product 24 (52.4 mg, 0.13 mmol, 51%) was obtained as a colorless oil: [α]_D = −19.0 (c = 0.57, CHCl₃). ¹H NMR (500 MHz, CDCl₃, simulated ring coupling constants using DAISY) δ_H 7.84–7.81 (m, 2H, Ar), 7.76–7.74 (m, 2H, Ar), 7.34–7.16 (m, 10H, Ar), 4.91 (ddd, J = 2.5, 3.3 Hz, ³J_PH = 9.0 Hz, 1H, 4-H), 4.55–4.50 (m, 2H, 1-H, 1’-H_b), 4.35 (m, 1H, 1’-H_a), 4.08 (ddddd, J = 6.5, 6.5, 6.5, 2.5 Hz, ⁴J_PH = 2.0 Hz, 1H, 5-H), 3.61 (dd, J = 7.9, 5.0 Hz, 1H, 2-H), 3.43 (dd, J = 7.9, 3.3 Hz, 1H, 3-H), 3.42 (s, 3H, OMe), 3.39 (s, 3H, OMe), 1.19 ppm (d, J = 6.5 Hz, 3H, 6-H₃). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.3 (2 × C, CO), 150.7 (d, ²J_PC = 7.4 Hz, C, Ar), 150.5 (d, ²J_PC = 6.4 Hz, C, Ar), 134.5 (2 × CH, Ar), 129.7 (2 × CH, Ar), 129.5 (2 × CH, Ar), 128.8 (2 × C, Ar), 125.2 (CH, Ar), 125.1 (CH, Ar), 123.5 (2 × CH, Ar), 120.3 (CH, Ar), 120.2 (CH, Ar), 120.1 (CH, Ar), 120.0 (CH, Ar), 78.4 (CH, C-3), 76.5 (d, ²J_PC = 6.4 Hz, CH, C-4), 75.9 (CH, C-2), 73.8 (CH₂, C-1’), 70.3 (CH, C-1), 68.1 (d, ³J_PC = 6.3 Hz, CH, C-5), 59.4 (CH₃, OMe), 57.9 (CH₃, OMe), 15.4 ppm (CH₃, C-6). IR (CHCl₃): ν = 3026, 2938, 1792, 1734, 1210 cm^–1. MS (ESI) m/z (%) = 606 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₂₉H₃₀NNaO₁₀P: 606.1505; found 606.1500. Anal. calcd for C₂₉H₃₀NO₁₀P: C, 59.69; H, 5.18; N, 2.40. Found: C, 59.61; H, 5.23; N, 2.70.

C-(2,3-Di-O-methyl-α-l-rhamnopyranosyl)N-methoxyphthalimide (105)

To a solution of 104 (570 mg, 1.92 mmol) in dry EtOAc (45 mL) was added Pd/C 10% (430 mg), and the mixture was submitted to a H₂ atmosphere overnight. The reaction was filtered over a pad of Celite and evaporated. The residue was then submitted to the general procedure to give phthalimide 105 (383 mg, 1.09 mmol, 57%) as a colorless oil: [α]_D = −22.6 (c = 1.34, CHCl₃). ¹H NMR (500 MHz, CDCl₃) δ_H 7.84–7.82 (m, 2H, Ar), 7.76–7.74 (m, 2H, Ar), 4.53 (dd, J = 11.0, 4.9 Hz, 1H, 1’-H_b), 4.32 (dd, J = 11.0, 4.7 Hz, 1H, 1’-H_a), 4.24 (ddd, J = 4.7, 4.7, 4.7 Hz, 1H, 1-H), 4.07 (dd, J = 5.1, 3.3 Hz, 1H, 2-H), 3.70–3.67 (m, 2H, 4-H, 5-H), 3.60 (dd, J = 7.2, 3.3 Hz, 1H, 3-H), 3.52 (s, 3H, OMe), 3.50 (s, 3H, OMe), 1.28 ppm (d, J = 6.3 Hz, 3H, 6-H₃), 1H from OH is missing. ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 163.4 (2 × C, CO), 134.6 (2 × CH, Ar), 128.7 (2 × C, Ar), 123.6 (2 × CH, Ar), 79.5 (CH, C-3), 76.4 (CH₂, C-1’), 73.6 (CH, C-2), 72.8 (CH, C-4 or C-5), 70.5 (CH, C-4 or C-5), 70.3 (CH, C-1), 57.7 (CH₃, OMe), 57.5 (CH₃, OMe), 16.9 ppm (CH₃, C-6). IR (CHCl₃): ν = 3674, 3501, 3022, 2937, 1792, 1735, 1212 cm^–1. MS (ESI) m/z (%) = 374 (100) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₁₇H₂₁NNaO₇: 374.1216; found 374.1213. Anal. calcd for C₁₇H₂₁NO₇: C, 58.11; H, 6.02; N, 3.99. Found: C, 58.22; H, 6.18; N, 4.11.

Methyl 4-O-Benzyl-6-O-tert-butyldiphenylsilyl-2,3-di-O-methyl-α-d-[4-O-PhCH-²H]galactopyranoside ([PhCH-²H]97)

A mixture of 96 (47.4 mg, 0.10 mmol) and benzyl α-[²H]-4-methylbenzenesulfonate⁵² (31.6 mg, 0.12 mmol, ²H/¹H 6.9:1) in DMF (0.2 mL) and CH₂Cl₂ (0.2 mL) was cooled to 0 °C. Then, sodium hydride (60% dispersion in mineral oil, 8 mg, 0.20 mmol) was added to the mixture, and the reaction was gradually warmed up to room temperature. After stirring for 1 h, the Dowex 50WX4-200 was added to quench the reaction. The mixture was filtered through a pad of Celite, and the filtrate was evaporated under reduced pressure. The crude residue was purified by column chromatography (hexanes–EtOAc, 8:2 to 7:3) to obtain the product [PhCH-²H]97 (28.6 mg, 0.05 mmol, 50%, ²H/¹H 7:1) as a colorless oil: ¹H NMR (500 MHz, CDCl₃) δ_H 7.67–7.60 (m, 4H, Ar), 7.46–7.32 (m, 6H, Ar), 7.31–7.21 (m, 5H, Ar), 4.91 (d, J = 11.4 Hz, 0.1H, O-CH₂-Ph), 4.900 (br s, 0.4H, O-CHD-Ph), 4.84 (d, J = 3.6 Hz, 1H, 1-H), 4.60 (d, J = 11.5 Hz, 0.1H, O-CH₂-Ph), 4.589 (br s, 0.4H, O-CHD-Ph), 4.01 (br s, 1H, 4-H), 3.79–3.69 (m, 4H, 6-H₂, 2-H, 5-H), 3.56 (dd, J = 10.1, 2.8 Hz, 1H, 3-H), 3.51 (s, 3H, 3-OMe), 3.51 (s, 3H, 2-OMe), 3.32 (s, 3H, 1-OMe), 1.06 ppm (s, 9H). ¹³C{¹H} NMR (125.7 MHz, CDCl₃) δ_C 138.6 (C, Ar), 135.56 (2 × CH, Ar), 135.53 (2 × CH, Ar), 133.4 (2 × C, Ar), 129.74 (CH, Ar), 129.71 (CH, Ar), 128.2 (2 × CH, Ar), 128.1 (2 × CH, Ar), 127.71 (2 × CH, Ar), 127.70 (2 × CH, Ar), 127.5 (CH, Ar), 97.7 (CH, C-1), 80.8 (CH, C-3), 78.1 (CH, C-2), 74.73 (0.12CH₂, O-CH₂-Ph), 74.35 (0.88CH, t, J_CD = 22.1 Hz, O-CHD-Ph), 73.64 (0.12CH, C-4), 73.59 (0.44CH, C-4), 73.56 (0.44CH, C-4), 70.7 (CH, C-5), 62.8 (CH₂, C-6), 58. 8 (CH₃, OMe), 58.3 (CH₃, OMe), 55.0 (CH₃, OMe), 26.9 (3 × CH₃, DPS), 19.2 ppm (C, DPS). ¹H NMR (500 MHz, C₆D₆) δ_H 7.84–7.79 (m, 2H, Ar), 7.79–7.74 (m, 2H, Ar), 7.35 (m, 2H, Ar), 7.23–7.07 (m, 9H, Ar), 5.07 (d, J = 11.4 Hz, 0.1H, O-CH₂-Ph), 5.05 (br s, 0.4H, O-CHD-Ph), 4.82 (d, J = 3.6 Hz, 1H, 1-H), 4.61 (d, J = 11.4 Hz, 0.1H, O-CH₂-Ph), 4.58 (br s, 0.4H, O-CHD-Ph), 4.105 (dd, J = 10.0, 6.6 Hz, 0.5H, 6-H), 4.107 (dd, J = 10.1, 6.5 Hz, 0.5H, 6-H), 4.06 (dd, J = 10.1, 3.7 Hz, 0.5H, 6-H), 4.05 (dd, J = 10.2, 3.8 Hz, 0.5H, 6-H), 3.97–3.90 (m, 3H, 5-H, 4-H, 2-H), 3.73 (dd, J = 10.0, 2.9 Hz, 1H, 3-H), 3.35 (s, 3H, 3-OMe), 3.232 (s, 1.5H, 2-OMe), 3.230 (s, 1.5H, 2-OMe), 3.21 (s, 3H, 1-OMe), 1.19 ppm (s, 9H). ¹³C{¹H} NMR (125.7 MHz, C₆D₆) δ_C 139.98 (C, Ar), 136.41 (2 × CH, Ar), 136.31 (2 × CH, Ar), 134.33 (C, Ar), 134.16 (C, Ar), 130.42 (CH, Ar), 130.40 (CH, Ar), 98.93 (CH, C-1), 81.71 (CH, C-3), 79.40 (CH, C-2), 75.55 (0.12CH, C-4), 75.51 (0.44CH, C-4), 75.48 (0.44CH, C-4), 75.45 (0.12CH₂, O-CH₂-Ph), 75.08 (0.44CH, t, J_CD = 22.1 Hz, O-CHD-Ph), 75.05 (0.44CH, t, J_CD = 21.1 Hz, O-CHD-Ph), 71.89 (CH, C-5), 64.14 (CH₂, C-6), 59.00 (CH₃, OMe), 58.59 (CH₃, OMe), 55.26 (CH₃, OMe), 27.46 (3 × CH₃, DPS), 19.81 ppm (C, DPS), some aromatic carbons were not observed. IR (CHCl₃): ν = 3020, 2932, 1471, 1428, 1220, 1103 cm^–1. MS (ESI) m/z (%) = 574 (100) [M + Na]⁺, 573 (13) [M + Na]⁺. HRMS (ESI) m/z: [M + Na]⁺ calcd for C₃₂H₄₁²HNaO₆Si 574.2711; found 574.2716; [M + Na]⁺ calcd for C₃₂H₄₂NaO₆Si 573.2648; found 573.2653.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.1c01376.

• Tables of calculated ring coupling constants (³J_H,H) of starting phthalimides and final bicyclic ketals; calculated long-range ⁴J_w coupling constants; selected signals of ¹H and ¹³C{1H} NMR spectra of labeled [PhCH-²H]31 and [PhCH-²H]97; reactivity differences between LGs in the 1,5-hydrogen atom transfer/Surzur–Tanner rearrangement sequence; and copies of the ¹H and ¹³C{1H} NMR spectra of all new compounds (PDF)

The authors declare no competing financial interest.