Tethered Silanoxyiodination of Alkenes

Abstract

We present the first examples of tethered silanoxyiodination reactions of allylic alcohols. The products are useful silanediol organoiodide synthons and are formed with high regioselectivity and diastereocontrol. The reaction is scalable greater than 10-fold without loss of yield or selectivity. Furthermore, the products are starting materials for further transformations, including de-iodination, C─N bond installation, epoxide synthesis, and de-silylation. DFT calculations provide a basis for understanding the exquisite 6-endo selectivity of this silanoxyiodination reaction and show that the observed products are both kinetically and thermodynamically preferred.

Graphical Abstract

Tethered alkene functionalization reactions allow the synthetic chemist to transform olefins with unusual precision.^1-7 Because of the predisposition for six- and seven-membered cyclic transition states, one can simply count the number of atoms from the nucleophilic auxiliary (“the tether”) where the functionalization event is likely to take place; due to geometric constraints, these reactions generally proceed with high regio- and diastereoselectivity. Our laboratory is deeply invested in developing tethered olefin functionalization reactions, and we have disclosed such reactions using sulfamate,^{8, 9} phosphoramidate,¹⁰ and di-tert-butyl-silanoxy tethers.^{11, 12}

Iodofunctionalization of olefins is a particularly powerful method for the synthesis of organoiodides, which are versatile precursors for C─O,¹³ C─N,¹⁴ and C─C bonds¹⁵ (Scheme 1). Two particularly well-known classes within this large area are iodolactonization^16-20 and iodoetherification^21-24 of olefins (Scheme 2), and examples of both are found in complex molecule syntheses. Building on this precedent, we imagined a silanoxyiodination reaction, which would yield protected diol iodides in a single step and with high regio- and diastereoselectivity. We reasoned that the di-tert-butyl silyl group could be facilely removed to reveal useful iodo-diol synthons. Here, we describe our efforts to reduce this idea to practice.

Scheme 1.

Organoiodides have proven versatility.

Scheme 2.

Elegant work with iodolactonization and iodoetherification inspired this tethered silanoxyiodination.

Optimization of this tethered silanoxyiodination reaction began with (E)-di-tert-butyl(hex-2-en-1-yloxy)silanol, conveniently prepared in one step from commercially available di-tert-butylsilyl bis(trifluoromethanesulfonate) and trans-2-hexen-1-ol.¹¹ With I₂ (3 equivalents) and NaHCO₃ (6 equivalents) in acetonitrile at 0 °C, we were pleased to observe 65% of desired product (Table 1, Entry 1). However, we soon discovered that these conditions were much too corrosive with other allylic silanols and led to markedly reduced product yields. The use of Ag (I) in conjunction with I₂ is well known for the mild generation of I⁺.^{21, 23, 25} With AgNO₃/I₂ (Table 1, Entry 2) and with Ag(TFA)/I₂ (Table 1, Entry 3), we did not observe any cyclized product formation. In both cases, we isolated linear alkyl iodide products, which we presume result from intermolecular opening of the transient iodonium intermediate by NO₃^- and CF₃CO₂⁻. We hypothesized that switching to a silver salt with a non-nucleophilic counterion would eliminate intermolecular ring-opening. With AgBF₄ in acetonitrile, tetrahydrofuran, or ethyl acetate (Table 1, Entries 4-6) at 0°C, we observed ~60% cyclized product formation. Using CH₂Cl₂ as a solvent was markedly deleterious (Table 1, Entry 7). In THF, when the temperature was reduced from 0 °C to −15 °C, the yield of cyclized product increased slightly (Table 1, Entry 8); however, dropping the temperature further to −45 °C led to a dramatic decrease in product formation (Table 1, Entry 9). We found that Ag(OTf)/I₂ in THF, Ag(OTf)/I₂ in DME, and AgBF₄/I₂ in DME at −15 °C (Table 1, Entries 10-12) all gave comparable, good yields of cyclized product. Overall, we chose three protocols (A: AgBF₄/I₂/THF, B: AgBF₄/I₂/DME, C: AgOTf/I₂/DME) for further exploration of scope.

Table 1.

Optimization of a tethered silanoxyiodination reaction.

	Ag (I) (equiv.)	I2 equiv.	Solvent	Temp.a	B/Ab
1	None	3c	MeCN	0 °C	65/0
2	AgNO3 (1)	1	MeCN	0 °C	0/0d
3	Ag(TFA) (1)	1	MeCN	0 °C	0/0e
4	AgBF4 (1)	1	MeCN	0 °C	58/0
5	AgBF4 (1)	1	THF	0 °C	60/0
6	AgBF4 (1)	1	EtOAc	0 °C	62/11
7	AgBF4 (1)	1	CH2Cl2	0 °C	22/0
8	AgBF4 (1)	1	THF	−15 °C	65/0
9	AgBF4 (1)	1	THF	−45 °C	45/0
10	AgOTf (1)	1	THF	−15 °C	70/0
11	AgBF4 (1)	1	DME	−15 °C	75/0
12	AgOTf (1)	1	DME	−15 °C	80/0

^areaction times were between 1 and 2 hours in all cases.

^bYield estimated from ¹H NMR integration with methyl phenyl sulfone as an internal standard.

^cWith 6 equivalents of NaHCO₃.

^dTwo non-cyclized products, which we presume result from NO₃⁻ opening of the iodonium intermediate.

^eTwo non-cyclized products, which we presume result from CF₃CO₂⁻ opening of the iodonium intermediate.

Examination of a variety of allylic silanol substrates (Scheme 3) with these protocols revealed that this transformation is quite general, tolerant of diverse functional groups, and in most cases, proceeds with high regio- and diastereoselectivity. We have determined the relative configuration of one of these products through X-ray diffraction analysis, which establishes that the iodine and the pendant alkyl chain are trans to each other (Scheme 3, Entry 11, CCDC: 2062814). While protocol A (AgBF₄/I₂/THF) gave good product yields with several substrates (Scheme 3, Entries 1 and 7), a curious side product complicated crude NMR analysis and purification. Amazingly, this side product has been previously characterized and arises from a ring-opening polymerization of THF by I₂!²⁶ We thus abandoned THF in favor of DME, and we recommend that for substrates not shown here, both protocol B (AgBF₄/I₂/DME) and protocol C (AgOTf/I₂/DME) should be empirically tested for best results. We were pleased to find that a variety of alkyl chains (Scheme 3, Entries 1, 2, & 6), rings (Scheme 3, Entries 3-4), alkyl ethers (Scheme 3, Entry 3), ketals (Scheme 3, Entry 5), esters (Scheme 3, Entry 10), aromatic rings (Scheme 3, Entries 8 & 11), and heteroaromatic rings (Scheme 3, Entries 9 & 12) were all tolerated by our optimized protocols. Furthermore, we were not limited to disubstituted olefins. A variety of tri-substituted olefins (Scheme 3, Entries 13-15) reacted smoothly as well.

Scheme 3.

Substrate Scope.

We were pleased to see that the reaction scaled greater than ten-fold without loss of yield or selectivity (Scheme 4).

Scheme 4.

Silanoxyiodination scales greater than ten fold without loss of yield or selectivity.

Furthermore, the cyclic silanediol organoiodide products were amenable to a variety of further transformations, including, de-iodination, nucleophilic azide displacement, epoxide formation, and silicon removal (Scheme 5).

Scheme 5.

Products are versatile synthons for: (A) de-iodination (B) C-N bond formation (C) epoxide formation and (D) silicon removal.

In all cases, we exclusively observed products of 6-endo-trig cyclization reactions. In order to rationalize such exquisite selectivity for the 6-endo product over the 5-exo isomer, we turned to DFT calculations using the ORCA software package.^{27, 28} All calculations were performed using the B3LYP functional^{29, 30} with D3BJ dispersion correction^{31, 32} using the RIJCOSX approximation.³³ The def2-TZVP basis set³⁴ was used, and implicit THF solvation was applied using the SMD model.³⁵ When iodine was present, the def2-ECP³⁶ was applied automatically. Counterions were not modelled for ionic species. Further details and atomic coordinates are reported in the Supporting Information.

Upon exposing substrate alkene 1 to molecular iodine, the immediate product is an intermediate iodonium 61. Intramolecular ring closure can proceed either via a 5-exo (62) or a 6-endo (63) transition state, leading to isomeric protonated products 64 and 65. For the 5-exo pathway, both the transition state and the cationic product are more than 4 kcal/mol higher in energy than their 6-endo counterparts (Figure 1). This overwhelming preference for the 6-endo pathway agrees with the experimental absence of any 5-exo product, even in trace amounts. The origin of the 6-endo selectivity is most likely due to ring strain. For acyclic iodonium 61, the O-Si-O angle is 102.6°, which is 6.9° lower than the ideal tetrahedral angle of 109.5°. This initial acyclic perturbation is likely due to the presence of the tert-butyl groups on the silicon, a manifestation of the Thorpe-Ingold effect.³⁷ The 6-endo transition state 63 has an O-Si-O angle of 101.3°, and the 6-endo product 65 has an O-Si-O angle of 97.6°, the latter of which is only 5° smaller than the acyclic angle on iodonium 61. By contrast, the 5-exo transition state 62 has an O-Si-O angle of 96.7°, and the 5-exo product 64 has an O-Si-O angle of 89.8°, the latter of which is now geometrically acute and 12.8° smaller than the acyclic angle on iodonium 61. Thus, the tert-butyl groups on silicon promote a Si-O-Si angle close to that required for 6-endo ring closure, while 5-exo ring closure requires a much more strained and energetically unfavorable Si-O-Si angle.

Figure 1.

DFT energies for cationic iodonium rearrangements of substrate 1.

In summary, we present the first examples of tethered silanoxyiodination reactions of allylic alcohols. The products are useful silanediol organoiodide synthons and are formed with high regioselectivity and diastereocontrol. The reaction is scalable greater than 10-fold without loss of yield or selectivity. Furthermore, the products are starting materials for further transformations, including de-iodination, C─N bond installation, epoxide synthesis, and de-silylation. DFT calculations provide a basis for understanding the exquisite 6-endo selectivity of this silanoxyiodination reaction. We expect this reaction to find much use in the construction of complex molecules containing functional group stereochemical arrays.

Experimental Section

I. General Considerations:

All reagents were obtained commercially unless otherwise noted. Solvents were purified by passage under 10 psi N₂ through activated alumina columns. Infrared (IR) spectra were recorded on a Thermo Scientific™ Nicolet™ iS™5 FT-IR Spectrometer; data are reported in frequency of absorption (cm⁻¹). NMR spectra were recorded on a Bruker Avance 400 operating at 400 and 100 MHz. ¹H NMR spectra were recorded at 400 MHz. Data are recorded as: chemical shift in ppm referenced internally using residue solvent peaks, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet or overlap of nonequivalent resonances), integration, coupling constant (Hz). ¹³C NMR spectra were recorded at 100 MHz. Exact mass spectra were recorded using an electrospray ion source (ESI) either in positive mode or negative mode and with a time-of-flight (TOF) analyzer on a Waters LCT PremierTM mass spectrometer and are given in m/z. TLC was performed on pre-coated glass plates (Merck) and visualized either with a UV lamp (254 nm) or by dipping into a solution of KMnO₄−K₂CO₃ in water followed by heating. Flash chromatography was performed on silica gel (230-400 mesh) or Florisil (60-100 mesh).

II. Characterization of Previously Unreported Substrates

Note 1: Substrates were synthesized according to previously reported procedures. See Org. Lett. 2020, 22, 21, 8665–8669.

Note 2: Compounds 1-4, 6-8, 11, 13-17, 19, 20, 23, 25 have been reported in Org. Lett. 2020, 22, 21, 8665–8669 or in Chemrxiv 2021. https://doi.org/10.26434/chemrxiv.13679083.v1.

(E)-di-tert-butyl((6-methylhept-2-en-1-yl)oxy)silanol

Compound 5: Purified using a gradient of 0 to 10% EtOAc in hexanes on silica gel; (yellow oil, 476 mg, 83%); ¹H NMR (400 MHz, Chloroform-d) δ 5.69 (ddt, J = 14.1, 6.2, 1.2 Hz, 1H), 5.59 (dtt, J = 15.3, 5.3, 1.2 Hz, 1H), 4.35 – 4.28 (m, 2H), 2.12 – 2.01 (m, 2H), 1.58 (dq, J = 13.3, 6.7 Hz, 1H), 1.33 – 1.24 (m, 2H), 1.05 (s, 18H), 0.91 (d, J = 6.6 Hz, 6H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 131.6, 129.1, 64.2, 38.4, 30.0, 27.5, 27.42, 22.47, 20.46. IR 2857, 1457, 1173 cm⁻¹. HRMS (ESI) calculated for C₁₆H₃₃O₂Si⁻ 285.2250, Found 285.2245 (M⁻).

(E)-di-tert-butyl((3-(tetrahydro-2H-pyran-4-yl)allyl)oxy)silanol

Compound 9: purified using a gradient of 0 to 50% acetone/DCM; (light yellow oil, 403 mg, 67% yield); ¹H NMR (400 MHz, CDCl₃) δ 5.63 – 5.54 (m, 1H), 5.54 – 5.42 (m, 1H), 4.24 (tt, J = 4.8, 1.2 Hz, 2H), 3.89 (ddt, J = 12.5, 4.2, 1.6 Hz, 2H), 3.35 (tt, J = 11.6, 2.2 Hz, 2H), 2.20 – 2.12 (m, 1H), 1.55 (ddq, J = 12.8, 4.1, 2.0 Hz, 2H), 1.46 – 1.30 (m, 2H), 0.95 (s, 18H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 134.8, 134.4, 127.9, 127.6, 67.7, 64.1, 63.9, 37.3, 32.6, 32.5, 27.8, 27.4, 21.2, 20.4. IR 2933, 1473, 1127, 827, 648 cm⁻¹.; HRMS (ESI) calculated for C₁₆H₃₁O₃Si⁻ 299.2048 Found 299.2055 (M⁻).

tert-butyl (E)-4-(3-((di-tert-butyl(hydroxy)silyl)oxy)prop-1-en-1-yl)piperidine-1-carboxylate

Compound 10: Purified using a gradient of 0 to 10% EtOAc in hexanes on silica gel; (Colorless oil, 663 mg, 83%); ¹H NMR (400 MHz, Chloroform-d) δ 5.70 – 5.55 (m, 2H), 4.33 (dd, J = 4.8, 1.2 Hz, 2H), 4.11 (dt, J = 13.7, 3.6 Hz, 2H), 2.76 (ddd, J = 13.3, 12.2, 2.8 Hz, 2H), 2.14 (td, J = 10.8, 5.9 Hz, 1H), 1.74 – 1.65 (m, 2H), 1.48 (s, 9H), 1.37 – 1.25 (m, 2H), 1.05 (s, 18H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 154.9, 134.6, 128.0, 79.3, 63.9, 43.6, 38.4, 31.7, 28.4, 27.4, 20.4. IR 2857, 1457, 1173 cm⁻¹. HRMS (ESI) calculated for C₂₁H₄₁NO₄SiNa⁺ 422.2703, found mass 422.2692 (MNa⁺).

(S,E)-((3-(1,4-dioxaspiro[4.5]decan-2-yl)allyl)oxy)di-tert-butylsilanol

Compound 12: purified using a gradient of 0 to 20% EtOAc:Hexanes; (colorless oil, 420 mg, 59% yield); ¹H NMR (400 MHz, CDCl₃) δ 5.92 (dtd, J = 15.3, 4.5, 0.9 Hz, 1H), 5.75 (ddt, J = 15.4, 7.4, 1.7 Hz, 1H), 4.62 – 4.50 (m, 1H), 4.39 (ddd, J = 4.5, 1.7, 0.7 Hz, 2H), 4.14 – 4.09 (m, 1H), 3.68 – 3.53 (m, 1H), 1.72 – 1.58 (m, 9H), 1.43 (m, 1H), 1.05 (s, 18H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 133.4, 127.4, 109.8, 76.2, 69.1, 63.0, 36.2, 35.4, 27.4, 25.1, 23.9, 23.8, 20.5. IR 2866, 1465, 1082, 829 cm⁻¹. HRMS (ESI) calculated for C₁₉H₃₅O₄Si⁻ 355.2310 Found 355.2336 (M⁻).

(E)-((3-(4-bromophenyl)allyl)oxy)di-tert-butylsilanol

Compound 18: purified using a gradient of 0 to 0.2% Acetone in DCM; (light yellow oil, 319 mg, 43% yield); ¹H NMR (400 MHz, CDCl₃) δ 7.57 – 7.40 (m, 2H), 7.40 – 7.16 (m, 2H), 6.61 (dt, J = 15.9, 2.0 Hz, 1H), 6.33 (dt, J = 15.8, 4.9 Hz, 1H), 4.55 (dd, J = 4.9, 1.8 Hz, 2H), 1.09 (d, J = 0.9 Hz, 18H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 136.2, 131.7, 130.1, 128.2, 128.0, 121.1, 63.9, 27.5, 20.6. IR 3471, 2919, 1479, 1378, 829 cm⁻¹.; HRMS (ESI) calculated for C₁₇H₂₆BrO₂Si⁻ 369.0891 Found 369.0867 (M⁻).

(E)-4-((di-tert-butyl(hydroxy)silyl)oxy)but-2-en-1-yl acetate

Compound 21: purified using a gradient of 0 to 50% Acetone in DCM on silica gel followed by a gradient of 0 to 100% Acetonitrile in 0.1%TFA-H₂O on a RediSep Prep C18 column (100 Å, 5 μm, Length 250 mm ID: 20 mm, Flow rate of 15 mL/min); (light yellow oil, 288 mg, 50% yield); ¹H NMR (400 MHz, CDCl₃) δ 5.96 – 5.78 (m, 2H), 4.67 – 4.56 (m, 2H), 4.40 (dt, J = 4.0, 1.3 Hz, 2H), 2.10 (s, 3H), 1.06 (s, 18H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 171.1, 134.2, 123.3, 64.6, 63.0, 27.4, 20.9, 20.5. IR 3442, 2947, 1730, 1246, 829 cm⁻¹. HRMS (ESI) calculated for C₁₄H₂₇O₄Si⁻ 287.1684 Found 287.1661 (M⁻).

(E)-4-((di-tert-butyl(hydroxy)silyl)oxy)but-2-en-1-yl benzoate

Compound 22: purified using a gradient of 0 to 50% Acetone/DCM on silica gel; (light yellow semi-solid, 343 mg, 49% yield); ¹H NMR (400 MHz, CDCl₃) δ 8.09 – 7.98 (m, 2H), 7.60 – 7.53 (m, 1H), 7.44 (ddd, J = 8.2, 6.7, 1.2 Hz, 2H), 6.03 – 5.88 (m, 2H), 4.83 (tt, J = 2.3, 1.3 Hz, 2H), 4.40 (p, J = 1.4 Hz, 2H), 1.03 (s, 18H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 166.6, 134.2, 133.0, 130.3, 129.7, 128.4, 123.7, 65.0, 63.2, 27.5, 20.6. IR 3447, 2933, 1704, 1279, 827 cm⁻¹.; HRMS (ESI) calculated for C₁₉H₂₉O₄Si⁻ 349.1841 Found 349.1813 (M⁻).

(E)-di-tert-butyl((3-(pyridin-3-yl)allyl)oxy)silanol

Compound 24: Purified using a gradient of 0 to 10% EtOAc in hexanes on silica gel; (Colorless oil, 411 mg, 70%); ¹H NMR (400 MHz, Chloroform-d) δ 8.60 (d, J = 2.2 Hz, 1H), 8.47 (dd, J = 4.9, 1.6 Hz, 1H), 7.71 (dt, J = 7.9, 1.9 Hz, 1H), 7.27 (dd, J = 7.9, 4.9 Hz, 1H), 6.65 (dd, J = 15.9, 1.8 Hz, 1H), 6.40 (ddd, J = 16.0, 5.1, 4.2 Hz, 1H), 4.58 (dd, J = 4.7, 1.9 Hz, 2H), 1.10 (s, 18H). ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 148.0, 147.9, 133.0, 132.9, 131.9, 125.3, 123.5, 63.6, 27.4, 20.5. IR 2856, 1471, 1134 cm⁻¹. HRMS (ESI) calculated for C₁₆H₂₈NO₂Si⁺ 294.1884 found 294.1852 (MH⁺).

di-tert-butyl((3-ethylpent-2-en-1-yl)oxy)silanol

Compound 26: Purified using a gradient of 0 to 10% EtOAc in hexanes on silica gel; (Colorless oil, 409 mg, 75%);¹H NMR (400 MHz, Chloroform-d) δ 5.32 (td, J = 6.5, 3.3 Hz, 1H), 4.40 (dd, J = 6.3, 1.2 Hz, 2H), 2.13 – 2.01 (m, 4H), 1.08-0.97 (m, 6H),1.05 (s, 18H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 144.6, 122.7, 60.1, 28.9, 27.4, 23.6, 20.4, 13.3, 12.5. IR 2933, 1471, 1107 cm⁻¹. HRMS (ESI) calculated for C₁₅H₃₁O₂Si⁺ 271.2093 found 271.2091 (M⁺).

(E)-di-tert-butyl((3,7,11,15-tetramethylhexadec-2-en-1-yl)oxy)silanol

Compound 27: purified using a gradient of 0 to 0.1% acetone in DCM; (colorless oil, 400 mg, 44% yield); ¹H NMR (400 MHz, CDCl₃) δ 5.37 (tq, J = 6.3, 1.3 Hz, 1H), 4.39 (dq, J = 6.4, 0.9 Hz, 2H), 2.05 – 1.96 (m, 2H), 1.65 (t, J = 0.8 Hz, 3H), 1.56 (dp, J = 13.3, 6.6 Hz, 1H), 1.49 – 1.08 (m, 18H), 1.05 (s, 18H), 0.89 (ddd, J = 8.5, 6.6, 0.7 Hz, 12H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 137.4, 124.3, 60.4, 39.8, 39.3, 37.4, 37.4, 37.3, 36.6, 32.8, 32.7, 27.9, 27.4, 25.1, 24.8, 24.4, 22.7, 22.6, 20.4, 19.7, 19.7, 16.2. IR 2928, 1471, 1364, 1099, 827 cm⁻¹.; HRMS (ESI) calculated for C₂₈H₅₈NaO₂Si⁺ 477.4098 Found 477.4067 (MNa⁺).

di-tert-butyl(2-(tetrahydro-4H-pyran-4-ylidene)ethoxy)silanol

Compound 28: Purified using a gradient of 0 to 10% EtOAc in hexanes on silica gel; (Colorless oil, 401 mg, 70%); ¹H NMR (400 MHz, Chloroform-d) δ 5.44 (tt, J = 6.6, 1.3 Hz, 1H), 4.39 (d, J = 6.5 Hz, 2H), 3.71 (dt, J = 13.3, 5.5 Hz, 4H), 2.36 – 2.29 (m, 2H), 2.29 – 2.22 (m, 2H), 1.98 (s, 1H), 1.05 (s, 18H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 136.3, 123.1, 69.4, 68.5, 59.1, 36.6, 29.9, 27.3, 20.4. IR 2933, 1471, 1107 cm⁻¹. HRMS (ESI) calculated for C₁₅H₃₀O₃SiNa⁺ 309.1856 found 309.1821 (MNa⁺).

III. General Protocols for Silanoxyiodination of Alkenes

Protocol A: A microwave vial was charged with stir bar, alkene substrate (0.2 mmol, 1 equivalent), AgBF₄ (39 mg, 0.2 mmol, 1 equivalent) and 2 mL of anhydrous THF. The reaction vial was immersed in a bath set to −15 °C. I₂ (51 mg, 0.2 mmol, 1 equivalent) was added in 1 portion. A light-yellow precipitate formed immediately upon addition of AgBF₄. The heterogeneous mixture was stirred for 1 h at −15 °C and then quenched by addition of aqueous saturated Na₂S₂O₃. The reaction mixture was diluted with ethyl acetate and transferred to a separatory funnel. The organic portion was collected, and the aqueous layer was extracted with two additional portions of ethyl acetate. The organic fractions were pooled, dried with MgSO₄, and concentrated under reduced pressure. The resulting residue was purified by chromatography on Florisil (specific conditions are associated with each compound).

Protocol B: A microwave vial was charged with stir bar, alkene substrate (0.2 mmol, 1 equivalent), AgBF₄ (39 mg, 0.2 mmol, 1 equivalent) and 2 mL of anhydrous DME. The reaction vial was immersed in a bath set to −15 °C. I₂ (51 mg, 0.2 mmol, 1 equivalent) was added in 1 portion. A light-yellow precipitate formed immediately upon addition of AgBF₄. The heterogeneous mixture was stirred for 1 h at −15 °C and then quenched by addition of aqueous saturated Na₂S₂O₃. The reaction mixture was diluted with ethyl acetate and transferred to a separatory funnel. The organic portion was collected, and the aqueous layer was extracted with two additional portions of ethyl acetate. The organic fractions were pooled, dried with MgSO₄, and concentrated under reduced pressure. The resulting residue was purified by chromatography on Florisil (specific conditions are associated with each compound).

Protocol C: A microwave vial was charged with stir bar, alkene substrate (0.2 mmol, 1 equivalent), AgOTf (51 mg, 0.2 mmol, 1 equivalent) and 2 mL of anhydrous DME. The reaction vial was immersed in a bath set to −15 °C. I₂ (51 mg, 0.2 mmol, 1 equivalent) was added in 1 portion. A light-yellow precipitate formed immediately upon addition of AgOTf. The heterogeneous mixture was stirred for 1 h at −15 °C and then quenched by addition of aqueous saturated Na₂S₂O₃. The reaction mixture was diluted with ethyl acetate and transferred to a separatory funnel. The organic portion was collected, and the aqueous layer was extracted with two additional portions of ethyl acetate. The organic fractions were pooled, dried with MgSO₄, and concentrated under reduced pressure. The resulting residue was purified by chromatography on Florisil (specific conditions are associated with each compound).

IV. Characterization of Iodinated Products

2,2-di-tert-butyl-5-iodo-4-methyl-1,3,2-dioxasilinane

Compound 29: synthesized using protocol C; single diastereomer; purified using benzene on Florisil; (light yellow semi-solid, 66 mg, 92% isolated yield); ¹H NMR (400 MHz, CDCl₃) δ 4.31 (dq, J = 10.2, 6.0 Hz, 1H), 4.27 – 4.16 (m, 2H), 4.01 (td, J = 10.5, 5.2 Hz, 1H), 1.53 (d, J = 6.0 Hz, 3H), 1.07 (s, 9H), 1.01 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 75.7, 71.0, 34.2, 27.4, 26.9, 24.8, 22.7, 19.8. IR 2960, 1474, 1136, 825 cm⁻¹.; HRMS (ESI) calculated for C₁₂H₂₆IO₂Si⁺ 357.0741 Found 357.0740 (MH⁺).

2,2-di-tert-butyl-5-iodo-4-propyl-1,3,2-dioxasilinane

Compound 30: synthesized using protocol A; single diastereomer; Light yellow solid; purified using a gradient of 0 to 10% EtOAc in Hexanes on silica gel; 54 mg, 70% isolated yield; ¹H NMR (400 MHz, CDCl₃) δ 4.20 – 4.09 (m, 2H), 4.05 (ddd, J = 10.2, 8.0, 2.2 Hz, 1H), 3.98 (td, J = 10.4, 4.9 Hz, 1H), 2.02 – 1.91 (m, 1H), 1.52 – 1.32 (m, 3H), 0.97 (s, 9H), 0.91 (s, 9H), 0.88 (t, J = 7.2 Hz, 3H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 78.3, 71.3, 39.8, 33.2, 27.4, 26.9, 22.8, 19.9, 17.9, 13.7. IR 2960, 1474, 1135, 825 cm⁻¹. HRMS (ESI) calculated for C₁₄H₃₀IO₂Si⁺ 385.1054 Found 385.1057 (MNa⁺).

2,2-di-tert-butyl-5-iodo-4-nonyl-1,3,2-dioxasilinane

Compound 31: synthesized using protocol A; single diastereomer; purified using benzene on Florisil; (colorless oil, 64 mg, 68% isolated yield); ¹H NMR (400 MHz, CDCl₃) δ 4.20 – 4.08 (m, 2H), 4.08 – 3.93 (m, 2H), 2.04 – 1.92 (m, 1H), 1.50 – 1.14 (m, 15H), 0.97 (s, 9H), 0.92 (s, 9H), 0.85 – 0.77 (m, 3H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 78.5, 71.3, 37.6, 33.3, 31.9, 29.5, 29.3, 29.1, 27.4, 26.9, 24.5, 22.8, 22.7, 19.9, 14.1. IR 2927, 1473, 1133, 825 cm⁻¹. HRMS (ESI) calculated for C₂₀H₄₂IO₂Si⁺ 469.1993 Found 469.1993 (MH⁺).

(±) 2,2-di-tert-butyl-5-iodo-4-isobutyl-1,3,2-dioxasilinane

Compound 32: synthesized using protocol B; single diastereomer; purified using 100% benzene on Florisil; (Colorless oil, 52 mg, 65%); ¹H NMR (400 MHz, Chloroform-d) δ 4.28 – 4.12 (m, 3H), 3.97–4.05 (m, 1H), 2.00 – 1.84 (m, 2H), 1.44 – 1.37 (m, 1H), 1.05 (s, 9H), 0.99 (s, 9H), 0.96 (d, J = 6.5 Hz, 3H), 0.94 (d, J = 6.3 Hz, 3H). ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 77.2, 71.2, 46.8, 34.1, 27.4, 26.9, 24.3, 23.7, 22.8, 21.1, 19.8. IR 2957, 1364, 903 cm⁻¹. HRMS (ESI) calculated for C₁₅H₃₂IO₂Si⁺ 399.1216 found 399.1253 (MH⁺).

2,2-di-tert-butyl-5-iodo-4-isopentyl-1,3,2-dioxasilinane

Compound 33: synthesized using protocol B; purified using 100% benzene on Florisil; single diastereomer; (Colorless oil, 73 mg, 89%);¹H NMR (400 MHz, Chloroform-d) δ 4.29 – 4.02 (m, 4H), 2.14 – 2.04 (m, 1H), 1.63 – 1.46 (m, 2H), 1.43 – 1.26 (m, 2H), 1.05 (s, 9H), 1.00 (s, 9H), 0.93 (d, J = 4.9 Hz, 3H), 0.91 (d, J = 4.8 Hz, 3H). ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 78.7, 71.2, 35.4, 33.6, 33.3, 27.6, 27.4, 26.9, 23.0, 22.8, 22.2, 19.9. IR 2956, 1137, 896 cm⁻¹. HRMS (ESI) calculated for C₁₆H₃₄IO₂Si⁺ 413.1373 found 413.1370 (MH⁺).

2,2-di-tert-butyl-5-iodo-4-isopropyl-1,3,2-dioxasilinane

Compound 34: synthesized using protocol B; purified using benzene on Florisil; (light yellow semi-solid, 45 mg, 58% isolated yield); single diastereomer; ¹H NMR (400 MHz, CDCl₃) δ 4.32 (dd, J = 10.4, 4.2 Hz, 1H), 4.24 (t, J = 10.7 Hz, 1H), 4.21 – 4.12 (m, 1H), 4.02 (dd, J = 10.1, 2.0 Hz, 1H), 2.34 (pd, J = 6.8, 2.0 Hz, 1H), 1.07 (s, 9H), 1.04 (d, J = 6.4 Hz, 12H), 0.87 (d, J = 6.7 Hz, 3H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 81.7, 71.8, 33.0, 31.8, 27.6, 26.9, 23.0, 20.2, 20.0, 13.2. IR 2960, 1076, 1028, 764 cm⁻¹.; HRMS (ESI) calculated for C₁₄H₃₀IO₂Si⁺ 385.1060 Found 385.1052 (MH⁺).

(±) 4-(sec-butyl)-2,2-di-tert-butyl-5-iodo-1,3,2-dioxasilinane

Compound 35: synthesized using protocol B; purified using 100% benzene on Florisil; ~1:1 mixture of diastereomers; (Colorless oil, 38 mg, 48%);¹H NMR (400 MHz, Chloroform-d) δ 4.36 – 4.27 (m, 1H), 4.27 – 4.14 (m, 2H), 4.08 – 4.00 (m, 1H), 2.07 (dddd, J = 18.4, 8.8, 5.1, 1.9 Hz, 1H), 1.56 – 1.46 (m, 1H), 1.46 – 1.34 (m, 1H), 1.24 – 1.14 (m, 1H), 1.07 (s, 4H), 1.06 (s, 5H), 1.04 (s, 1H), 1.03 (s, 4H), 1.02 (s, 5H), 0.97 (m, 3H), 0.87 (d, J = 6.7 Hz, 1H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 82.6, 79.8, 71.9, 71.8, 39.8, 39.7, 31.6, 31.5, 27.6, 27.5, 27.0, 26.9, 26.8, 23.0, 20.4, 20.2, 16.5, 12.0, 11.7, 11.4. IR 2859, 1474, 939 cm⁻¹. HRMS (ESI) calculated for C₁₅H₃₂IO₂Si⁺ 399.1216 found 399.1161 (MH⁺).

2,2-di-tert-butyl-4-cyclohexyl-5-iodo-1,3,2-dioxasilinane

Compound 36: synthesized using protocol B; purified using benzene on Florisil; (colorless semi-solid, 59 mg, 70% isolated yield); single diastereomer; ¹H NMR (400 MHz, CDCl₃) δ 4.34 – 4.17 (m, 3H), 3.98 (dt, J = 8.1, 2.1 Hz, 1H), 2.00 (td, J = 5.3, 2.5 Hz, 1H), 1.86 – 1.74 (m, 2H), 1.70 (dt, J = 12.6, 2.8 Hz, 1H), 1.59 (dd, J = 8.4, 3.2 Hz, 1H), 1.53 (td, J = 9.4, 3.4 Hz, 2H), 1.40 – 1.12 (m, 4H), 1.06 (s, 9H), 1.03 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 81.6, 71.8, 43.5, 31.1, 30.2, 27.6, 27.0, 26.5, 26.4, 26.0, 23.8, 23.0, 20.2. IR 2930, 1072, 1001, 975 cm⁻¹. HRMS (ESI) calculated for C₁₇H₃₄IO₂Si⁺ 425.1367 Found 425.1358 (MH⁺).

2,2-di-tert-butyl-5-iodo-4-(tetrahydro-2H-pyran-4-yl)-1,3,2 dioxasilinane

Compound 37: synthesized using protocol B; purified using a gradient of 0 to 40% EtOAc/benzene on Florisil; single diastereomer; (light yellow oil, 64 mg, 75% isolated yield); ¹H NMR (400 MHz, CDCl₃) δ 4.23 (dd, J = 10.1, 3.9 Hz, 1H), 4.19 – 4.03 (m, 2H), 4.01 – 3.90 (m, 3H), 3.43 – 3.27 (m, 2H), 2.17 (ttd, J = 11.8, 3.7, 2.0 Hz, 1H), 1.92 – 1.79 (m, 1H), 1.66 – 1.52 (m, 1H), 1.32 (dddt, J = 13.3, 11.5, 3.8, 2.1 Hz, 2H), 0.98 (s, 9H), 0.93 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 80.5, 71.6, 68.0, 67.7, 40.5, 30.1, 29.5, 27.6, 26.9, 23.9, 23.0, 20.2. IR 2857, 1163, 1080, 825 cm⁻¹.; HRMS (ESI) calculated for C₁₆H₃₂IO₃Si⁺ 427.1166 Found 427.1162 (MH⁺).

2,2-di-tert-butyl-5-iodo-1,3,2-dioxasilinan-4-yl)piperidine-1-carboxylate

Compound 38: synthesized using protocol B; purified using 100% benzene on Florisil; single diastereomer; (Colorless oil, 51 mg, 48%); ¹H NMR (400 MHz, Chloroform-d) δ 4.32 – 4.10 (m, 5H), 4.02 (dd, J = 10.1, 2.0 Hz, 1H), 2.70 (dd, J = 25.1, 13.4 Hz, 2H), 2.12 (ddddd, J = 13.6, 11.6, 9.7, 4.9, 2.0 Hz, 1H), 1.68 (dd, J = 28.2, 13.7 Hz, 1H), 1.52–1.45 (m, 3H), 1.47 (s, 9H), 1.03 (s, 9H), 0.98 (s, 9H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 154.9, 80.5, 79.3, 71.6, 43.9, 41.4, 30.3, 28.4, 27.5, 26.9, 23.0, 22.9, 20.1. IR 2933, 1423, 923 cm⁻¹. HRMS (ESI) calculated for C₂₁H₄₁INO₄Si⁺ 526.1850 found 526.1891 (MH⁺).

2,2-di-tert-butyl-5-iodo-4-methylcyclohexyl)-1,3,2-dioxasilinane

Compound 39: synthesized using protocol B; purified using benzene on Florisil; single diastereomer; (colorless oil, 63 mg, 72% yield); ¹H NMR (400 MHz, CDCl₃) δ 4.24 – 4.09 (m, 3H), 3.91 (dt, J = 8.8, 2.0 Hz, 1H), 1.88 – 1.78 (m, 1H), 1.67 (ddt, J = 13.6, 5.9, 1.9 Hz, 2H), 1.54 – 1.40 (m, 3H), 1.19 (dtt, J = 12.2, 9.0, 5.6 Hz, 3H), 0.96 (s, 9H), 0.92 (s, 9H), 0.94-0.84 (m, 1H), 0.81 (d, J = 6.5 Hz, 3H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 81.3, 71.8, 42.5, 35.0, 34.6, 32.7, 31.3, 30.0, 27.6, 27.0, 23.5, 23.0, 22.6, 20.2. IR 2928, 1455, 1117, 825 cm⁻¹. HRMS (ESI) calculated for C₁₈H₃₆IO₂Si⁺ 439.1524 Found 439.1516 (MH⁺).

2,2-di-tert-butyl-5-iodo-4-((R)-1,4 dioxaspiro[4.5]decan-2-yl)-1,3,2-dioxasilinane

Compound 40: synthesized using protocol B; purified using a gradient of 0 to 5% EtOAc:Hexanes on Florisil; single diastereomer; (colorless oil, 34 mg, 35% yield); ¹H NMR (400 MHz, CDCl₃) δ 4.45 (td, J = 6.7, 3.6 Hz, 1H), 4.30 (dd, J = 10.7, 3.6 Hz, 1H), 4.22 – 4.10 (m, 2H), 4.00 – 3.92 (m, 2H), 3.81 (td, J = 10.6, 5.2 Hz, 1H), 1.72 – 1.61 (m, 1H), 1.61 – 1.46 (m, 7H), 1.33 (s, 2H), 0.99 (s, 9H), 0.93 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 110.3, 79.2, 77.5, 71.6, 63.7, 35.7, 35.6, 27.5, 26.9, 26.4, 25.2, 24.0, 23.8, 23.0, 20.1. IR 2933, 1110, 1058, 825 cm⁻¹.; HRMS calculated for C₁₉H₃₆IO₄Si⁺ 483.1422 Found 483.1414.

2,2-di-tert-butyl-4-(2,6-dimethylheptyl)-5-iodo-1,3,2-dioxasilinane

Compound 41: synthesized using protocol C; purified using 100% benzene on Florisil; ~1:1 mixture of diastereomers; (Colorless oil, 61 mg, 65%); ¹H NMR (400 MHz, Chloroform-d) δ 4.29 – 4.15 (m, 3H), 4.06–3.99 (m, 1H), 2.03 (ddd, J = 13.6, 8.9, 2.1 Hz, 1.4H), 1.87 – 1.76 (m, 0.6H), 1.60–1.50 (m, 1H), 1.47 – 1.37 (m, 1H), 1.37 – 1.31 (m, 1H), 1.30 – 1.22 (m, 2H), 1.20 – 1.13 (m, 2H), 1.12 – 1.07 (m, 1H), 1.05 (s, 9H), 0.99 (s, 9H), 0.95 (d, J = 6.8 Hz, 1.8H), 0.92 (d, J = 6.2 Hz, 1.2H), 0.89 (d, J = 1.2 Hz, 3H), 0.87 (d, J = 1.0 Hz, 3H). ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 71.2, 71.2, 45.2, 44.7, 39.3, 39.1, 37.9, 35.6, 34.3, 29.3, 28.7, 27.9, 27.9, 27.44, 27.42, 26.9, 24.7, 24.4, 22.84, 22.81, 22.74, 22.70, 22.66, 22.59, 20.7, 19.8, 19.0. IR 2859, 1474, 906 cm⁻¹. HRMS (ESI) calculated for C₂₀H₄₂IO₂Si⁺ 469.1999 found 469.2005 (MH⁺).

2,2-di-tert-butyl-4-ethyl-5-iodo-1,3,2-dioxasilinane-6-d

Compound 42: synthesized using protocol A; purified using benzene on Florisil followed by eluting with 20% EtOAc/hexanes on a small plug of silica gel; mixture of diastereomers; (light yellow semi-solid, 46 mg, 62% isolated yield); ¹H NMR (400 MHz, CDCl₃) δ 4.18 – 4.05 (m, 1H), 4.04 – 3.94 (m, 2H), 2.03 (dqd, J = 14.8, 7.4, 1.8 Hz, 1H), 1.58 – 1.42 (m, 1H), 0.97 (s, 9H), 0.91 (d, J = 7.1 Hz, 12H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 79.5, 71.1 – 70.5 (m), 32.5, 30.6, 27.4, 26.9, 22.8, 19.9, 8.8. IR 2961, 1473, 1135, 827 cm⁻¹.; HRMS (ESI) calculated for C₁₃H₂₇DIO₂Si⁺ 372.0961 Found 372.0959 (MH⁺).

2,2-di-tert-butyl-4-hexyl-5-iodo-1,3,2-dioxasilinane-6-d

Compound 43: synthesized using protocol B; purified using benzene on Florisil; mixture of diastereomers; (light yellow semi-solid, 57 mg, 67% isolated yield); ¹H NMR (400 MHz, CDCl₃) δ 4.25 – 4.15 (m, 1H), 4.11 (ddd, J = 10.2, 7.8, 2.3 Hz, 1H), 4.08 – 4.00 (m, 1H), 2.13 – 1.99 (m, 1H), 1.57 – 1.45 (m, 2H), 1.38 – 1.19 (m, 7H), 1.04 (s, 9H), 0.99 (s, 9H), 0.92 – 0.87 (m, 3H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 78.7, 71.3 – 70.7 (m), 37.7, 33.3, 31.9, 29.0, 27.6, 27.0, 24.6, 23.0, 22.7, 20.0, 14.2. IR 2957, 1473, 1088, 827 cm⁻¹.; HRMS (ESI) calculated for C₁₇H₃₅DIO₂Si⁺ 428.1587 Found 428.1578 (MH⁺).

2,2-di-tert-butyl-5-iodo-4-phenyl-1,3,2-dioxasilinane

Compound 44: synthesized using protocol C; purified using 100% benzene on Florisil; single diastereomer; (Colorless oil, 66 mg, 79%);¹H NMR (400 MHz, Chloroform-d) δ 7.48 – 7.35 (m, 5H), 5.13 (d, J = 9.8 Hz, 1H), 4.48 – 4.30 (m, 3H), 1.14 (s, 18H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 142.4, 128.4, 128.1, 127.3, 82.0, 71.6, 34.2, 27.5, 27.0, 23.0, 20.2. IR 2859, 1471, 903 cm⁻¹. HRMS (ESI) calculated for C₁₇H₂₇IO₂SiNa⁺ 441.0717 found 441.0669 (MNa⁺).

2,2-di-tert-butyl-4-(4-fluorophenyl)-5-iodo-1,3,2-dioxasilinane

Compound 45: synthesized using protocol B; purified using 100% benzene on Florisil; single diastereomer; (Colorless oil, 61 mg, 70%); ¹H NMR (400 MHz, Chloroform-d) δ 7.46 – 7.35 (m, 2H), 7.14 – 7.03 (m, 2H), 5.11 (d, J = 10.3 Hz, 1H), 4.47 – 4.24 (m, 3H), 1.13 (s, 9H), 1.12 (s, 9H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 162.6 (d, J = 246.7 Hz), 138.4, 128.9 (d, J = 8.1 Hz), 115.0 (d, J = 21.3 Hz), 81.2, 71.5, 34.2, 27.5, 27.0, 23.0, 20.1. IR 2859, 1471, 1009 cm⁻¹. HRMS (ESI) calculated for C₁₇H₂₇FIO₂Si⁺ 437.0809 found 437.0796 (MH⁺).

4-(4-bromophenyl)-2,2-di-tert-butyl-5-iodo-1,3,2-dioxasilinane

Compound 46: synthesized using protocol B; purified using benzene on Florisil; single diastereomer; (colorless oil, 79 mg, 80% yield); ¹H NMR (400 MHz, CDCl₃) δ 7.47 – 7.33 (m, 2H), 7.22 – 7.12 (m, 2H), 4.94 (d, J = 10.3 Hz, 1H), 4.34 – 4.21 (m, 2H), 4.13 (td, J = 10.4, 5.3 Hz, 1H), 0.99 (s, 9H), 0.98 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 141.4, 131.3, 129.0, 122.3, 81.4, 71.5, 33.6, 27.5, 27.0, 23.0, 20.2. IR 2944, 1475, 1110, 827 cm⁻¹.; HRMS (ESI) calculated for C₁₇H₂₇BrIO₂Si⁺ 497.0003 Found 496.9971 (MH⁺).

4-(4--2,2-di-tert-butyl-5-iodo-1,3,2-dioxasilinan-4-yl)phenyl)morpholine

Compound 47: synthesized using protocol C; purified using 100% benzene on Florisil; single diastereomer; (Colorless oil, 50 mg, 50%);¹H NMR (400 MHz, Chloroform-d) δ 7.34 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.2 Hz, 2H), 5.10 – 4.97 (m, 1H), 4.47 – 4.31 (m, 3H), 3.95 – 3.85 (m, 4H), 3.22 (dd, J = 5.8, 3.9 Hz, 4H), 1.12 (s, 9H), 1.11 (s, 9H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 151.0, 134.0, 128.1, 114.9, 81.5, 71.5, 66.8, 49.0, 34.9, 27.5, 27.0, 23.0, 20.1. IR 2857, 1101, 932 cm⁻¹. HRMS (ESI) calculated for C₂₁H₃₅INO₃Si⁺ 504.1431 found 504.1426 (MH⁺).

4-(benzo[b]thiophen-3-yl)-2,2-di-tert-butyl-5-iodo-1,3,2-dioxasilinane

Compound 48: synthesized using protocol C; purified using 100% benzene on Florisil; single diastereomer; (Colorless oil, 37 mg, 39%); ¹H NMR (400 MHz, Chloroform-d) δ 8.01 (dd, J = 7.5, 1.3 Hz, 1H), 7.95 – 7.88 (m, 1H), 7.48 – 7.26 (m, 3H), 5.61 (d, J = 10.6 Hz, 1H), 4.70 (dt, J = 10.5, 7.9 Hz, 1H), 4.54 – 4.42 (m, 2H), 1.17 (s, 9H), 1.08 (s, 9H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 140.3, 137.9, 137.8, 124.4, 124.3, 123.9, 122.8, 122.5, 75.5, 71.5, 31.3, 27.5, 27.0, 23.0, 20.0. IR 2833, 1428, 1007 cm⁻¹. HRMS calculated for C₁₉H₂₈IO₂SSi⁺ 475.0624 found 475.0632 (MH⁺).

2,2-di-tert-butyl-5-iodo-1,3,2-dioxasilinan-4-yl)methyl acetate

Compound 49: synthesized using protocol B; purified using a gradient of 0 to 100% Acetone/DCM on Florisil followed by a gradient of 0 to 100% Acetonitrile in 0.1% TFA-H₂O on a RediSep Prep C18 column (100 Å, 5 μm, Length 250 mm, ID: 20 mm, Flow rate of 15 mL/min); single diastereomer; (light yellow oil, 60 mg, 72% yield); ¹H NMR (400 MHz, CDCl₃) δ 4.45 (dd, J = 11.8, 2.7 Hz, 1H), 4.27 (dd, J = 11.4, 3.6 Hz, 1H), 4.21 (dd, J = 11.8, 6.0 Hz, 1H), 4.12 (ddd, J = 7.6, 5.6, 3.6 Hz, 1H), 4.07 – 3.98 (m, 2H), 2.05 (s, 3H), 0.98 (s, 9H), 0.97 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 171.4, 71.5, 67.9, 66.2, 34.4, 27.5, 27.4, 20.9, 20.7, 20.5. IR 3442, 2947, 1730, 1246, 829 cm ⁻¹.; HRMS (ESI) calculated for C₁₄H₂₈IO₄Si⁺ 415.0796 Found 415.0788 (MH⁺).

2,2-di-tert-butyl-5-iodo-1,3,2-dioxasilinan-4-yl)methyl benzoate

Compound 50: synthesized using protocol B; purified using a gradient of 0 to 50% Acetone/DCM on Florisil followed by preparative TLC; single diastereomer; (light yellow oil, 34 mg, 36% yield); ¹H NMR (400 MHz, CDCl₃) δ 8.10 – 7.99 (m, 2H), 7.62 – 7.54 (m, 1H), 7.49 – 7.40 (m, 2H), 4.78 (dd, J = 11.9, 2.7 Hz, 1H), 4.54 (dd, J = 11.9, 5.8 Hz, 1H), 4.38 (dd, J = 11.4, 3.7 Hz, 1H), 4.28 (ddd, J = 7.4, 5.7, 3.7 Hz, 1H), 4.19 (ddd, J = 7.4, 5.8, 2.7 Hz, 1H), 4.14 (dd, J = 11.3, 5.7 Hz, 1H), 1.05 (s, 9H), 1.04 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 167.1, 133.5, 129.9, 129.7, 128.6, 71.8, 68.5, 66.3, 34.8, 27.6, 27.5, 20.8, 20.6. IR 3447, 2933, 1704, 1279, 827 cm⁻¹.; HRMS (ESI) calculated for C₁₉H₃₀IO₄Si⁺ 477.0953 Found 477.0985 (MH⁺).

2,2-di-tert-butyl-5-iodo-4-phenethyl-1,3,2-dioxasilinane

Compound 51: synthesized using protocol B; purified using a gradient of 0 to 10% EtOAc in hexanes on silica gel; single diastereomer; (light yellow solid, 69 mg, 77% isolated yield); ¹H NMR (400 MHz, CDCl₃) δ 7.25 – 7.19 (m, 2H), 7.17 – 7.09 (m, 3H), 4.20 – 4.14 (m, 1H), 4.14 – 4.06 (m, 1H), 4.03 – 3.98 (m, 2H), 2.79 (ddd, J = 14.1, 9.7, 4.6 Hz, 1H), 2.65 (ddd, J = 13.6, 9.4, 7.3 Hz, 1H), 2.37 (dddd, J = 13.6, 9.3, 7.3, 1.7 Hz, 1H), 1.81 – 1.66 (m, 1H), 0.97 (s, 9H), 0.94 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 141.8, 128.6, 128.3, 125.8, 77.7, 71.1, 39.4, 32.7, 31.0, 27.4, 27.0, 22.8, 19.9. IR 2931, 1174, 1042, 825 cm⁻¹. HRMS (ESI) calculated for C₁₉H₃₂IO₂Si⁺ 447.1211 Found 447.1208 (MH⁺).

2,2-di-tert-butyl-5-iodo-1,3,2-dioxasilinan-4-yl)pyridine

Compound 52: synthesized using protocol C; purified using 100% benzene on Florisil; single diastereomer; (Colorless oil, 42 mg, 50%); ¹H NMR (400 MHz, Chloroform-d) δ 8.61 (d, J = 2.3 Hz, 1H), 8.51 (dd, J = 4.8, 1.7 Hz, 1H), 7.65 (dt, J = 7.8, 1.9 Hz, 1H), 7.30 – 7.17 (m, 1H), 5.06 (d, J = 10.4 Hz, 1H), 4.39 – 4.26 (m, 2H), 4.19 (td, J = 10.3, 5.6 Hz, 1H), 1.02 (s, 9H), 1.02 (s, 9H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 149.7, 149.2, 137.7, 134.5, 123.1, 79.8, 71.4, 33.2, 27.5, 26.9, 23.0, 20.1. IR 2859, 1471, 937 cm⁻¹. HRMS (ESI) calculated for C₁₆H₂₇INO₂Si⁺ 420.0856 found 420.0845 (MH⁺).

2,2-di-tert-butyl-5-iodo-4,4-dimethyl-1,3,2-dioxasilinane

Compound 53: synthesized using protocol B; purified using a gradient of 0 to 10% EtOAc in hexanes on silica gel; (light yellow semi-solid, 59 mg, 80% isolated yield); ¹H NMR (400 MHz, CDCl₃) δ 4.29 (dd, J = 11.8, 3.8 Hz, 1H), 4.24 – 4.15 (m, 1H), 4.06 (dd, J = 11.1, 3.9 Hz, 1H), 1.50 (s, 3H), 1.43 (s, 3H), 0.94 (s, 9H), 0.93 (s, 9H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 75.2, 67.7, 37.1, 31.9, 27.3, 26.3, 21.5, 20.3. IR 2967, 1475, 1165, 825 cm⁻¹.; HRMS (ESI) calculated for C₁₃H₂₈IO₂Si⁺ 371.0898 Found 371.0899 (MH⁺).

2,2-di-tert-butyl-4,4-diethyl-5-iodo-1,3,2-dioxasilinane

Compound 54: synthesized using protocol B; purified using 100% benzene on Florisil; (Colorless oil, 47 mg, 59%); ¹H NMR (400 MHz, Chloroform-d) δ 4.54 (dd, J = 11.8, 4.5 Hz, 1H), 4.35 (t, J = 11.5 Hz, 1H), 4.16 (dd, J = 11.2, 4.5 Hz, 1H), 2.04 (dt, J = 14.7, 7.3 Hz, 1H), 1.89 (dqd, J = 14.6, 7.5, 2.4 Hz, 2H), 1.65 (dq, J = 14.8, 7.5 Hz, 1H), 1.05 (s, 9H), 1.03 (s, 9H), 1.06 – 0.98 (m, 6H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 77.8, 67.3, 35.2, 32.4, 28.4, 27.9, 27.3, 21.6, 21.0, 8.2, 8.2. IR 2860, 1475, 1145 cm⁻¹. HRMS (ESI) calculated for C₁₅H₃₂IO₂Si⁺ 399.1216 found 399.1181 (MH⁺).

2,2-di-tert-butyl-5-iodo-4-methyl-4-(4,8,12-trimethyltridecyl)-1,3,2-dioxasilinane

Compound 55: synthesized using protocol B; purified using benzene on Florisil; mixture of diastereomers; (light yellow oil, 81 mg, 70% yield); ¹H NMR (400 MHz, CDCl₃) δ 4.32 – 4.19 (m, 2H), 4.06 (dd, J = 8.9, 1.7 Hz, 1H), 1.84 (tdd, J = 13.1, 11.1, 4.6 Hz, 1H), 1.55 – 0.97 (m, 23H), 0.94 (d, J = 4.6 Hz, 18H), 0.79 (dd, J = 8.4, 6.6 Hz, 12H). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 76.6, 67.6, 44.2, 44.1, 39.4, 37.52, 37.50, 37.48, 37.45, 37.34, 37.28, 37.23, 37.21, 32.84, 32.82, 32.6, 32.5, 28.0, 27.5, 27.4, 24.83, 24.82, 24.48, 24.42, 23.79, 23.77, 22.75, 22.65, 21.4, 20.4, 20.0, 19.9, 19.83, 19.80, 19.77, 19.70. IR 2859, 1377, 1464, 1080, 825 cm⁻¹.; HRMS (ESI) calculated for C₂₈H₅₇INaO₂Si⁺ 603.3065 found 603.3049 (MNa⁺).

2,2-di-tert-butyl-5-iodo-1,3,9-trioxa-2-silaspiro[5.5]undecane

Compound 56: synthesized using protocol B; purified using 100% benzene on Florisil; (Colorless oil, 36 mg, 44%);¹H NMR (400 MHz, Chloroform-d) δ 4.35 – 4.16 (m, 2H), 4.06 (dd, J = 11.0, 3.4 Hz, 1H), 3.83 – 3.67 (m, 4H), 2.36 – 2.17 (m, 2H), 1.67 (dt, J = 13.6, 2.4 Hz, 1H), 1.34 (dt, J = 13.4, 2.3 Hz, 1H), 0.95 (s, 9H), 0.96 (s, 9H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 73.4, 66.6, 63.8, 63.0, 38.5, 37.5, 33.5, 27.5, 27.2, 21.5, 20.3. IR 2861, 1471, 924 cm⁻¹. HRMS (ESI) calculated for C₁₅H₂₉IO₃SiNa⁺ 435.0828 found 435.0851 (MNa⁺).

V. Scale-up Procedure

A round-bottom flask was charged with stir bar, alkene substrate (870 mg, 2.97 mmol, 1 equivalent), AgOTf (841 mg, 3.3 mmol, 1.3 equivalents) and 25 mL of anhydrous DME. The reaction vial was immersed in a bath set to −15 °C. I₂ (830 mg, 3.2 mmol, 1.2 equivalents) was added in 1 portion. A light-yellow precipitate formed immediately upon addition of AgOTf. The heterogeneous mixture was stirred for 2 h at −15 °C and then quenched by addition of aqueous saturated Na₂S₂O₃. The reaction mixture was diluted with ethyl acetate and transferred to a separatory funnel. The organic portion was collected, and the aqueous layer was extracted with two additional portions of ethyl acetate. The organic fractions were pooled, dried with MgSO₄, and concentrated under reduced pressure. The resulting residue was purified by chromatography on Florisil (100% benzene) to yield a light yellow solid (1.14 g, 2.72 mmol, 92% yield).

VI. Procedures for Derivatization Reactions

44 (70 mg, 0.16 mmol) was dissolved in 6 mL of DCM. Tributyltin hydride (97 μl, 0.36 mmol) was added, and reaction was stirred for 12 h at 40 °C (oil bath). The reaction mixture was concentrated, and the resulting residue was purified by chromatography on silica gel to yield 57 as a colorless oil (41 mg, 83%).

Compound 57: Purified using a gradient of 0 to 10% EtOAc in hexanes on silica gel; (Colorless oil, 83%); ¹H NMR (400 MHz, Chloroform-d) δ 7.48 – 7.35 (m, 4H), 7.35 – 7.26 (m, 1H), 5.22 (dd, J = 11.3, 2.3 Hz, 1H), 4.33 (ddd, J = 12.5, 11.1, 2.4 Hz, 1H), 4.21 (ddd, J = 11.0, 4.5, 2.0 Hz, 1H), 2.09 (dddd, J = 14.4, 12.5, 11.3, 4.5 Hz, 1H), 1.89 (dq, J = 14.4, 2.3 Hz, 1H), 1.15 (s, 9H), 1.13 (s, 9H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 144.9, 128.3, 127.0, 125.0, 75.9, 64.7, 39.5, 27.5, 27.2, 22.9, 20.1. IR 2859, 1473, 886 cm⁻¹. HRMS (ESI) calculated for C₁₇H₂₉O₂Si⁺ 293.1937 found 293.1938 (MH⁺).

44 (70 mg, 0.16 mmol) was dissolved in 0.5 ml of DMF. To this solution, sodium azide (0.32 mmol, 2 equiv.) and 15-Crown-5 (0.32 mmol, 2 equiv.) were added at room temperature. The temperature of the reaction was gradually increased to 100 °C (oil bath) and kept at this temperature for 12 hrs with magnetic stirring. After consumption of starting material (followed by TLC), the reaction mixture was diluted with EtOAc and transferred to a separatory funnel. The organic layer was washed with cold water (3 x 3 ml). The organic layer was collected, dried over Na₂SO₄, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel to yield compound 58 (24 mg, 43%) as a colorless solid.

Compound 58: Purified using benzene on Florisil; single diastereomer; (Colorless solid, 54%); ¹H NMR (400 MHz, Chloroform-d) δ 7.46 – 7.35 (m, 5H), 5.46 (d, J = 2.0 Hz, 1H), 4.56 (dd, J = 12.5, 1.8 Hz, 1H), 4.39 (dd, J = 12.5, 2.0 Hz, 1H), 3.82 (q, J = 1.9 Hz, 1H), 1.20 (s, 9H), 1.14 (s, 9H). ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 140.6, 128.2, 127.7, 125.7, 76.3, 66.1, 64.4, 27.7, 27.2, 23.5, 20.7. IR 2860, 1474, 889 cm⁻¹. HRMS (ESI) calculated for C₁₇H₂₈N₃O₂Si⁺ 334.1951 Found 334.1960 (MH⁺).

TBAF in THF (1 M, 0.280 mL, 0.28 mmol) was added to compound 44 (40 mg, 0.09 mmol) in THF (2 mL) at 0 °C, and the reaction was warmed to room temperature over 16 h. Following this time, the reaction mixture was concentrated, and the resulting residue was purified by chromatography on silica gel to yield 59 (9 mg, 63%) as a colorless oil.

Compound 59: Purified using a gradient of 0 to 20% EtOAc in hexanes on silica gel; single diastereomer; (Colorless oil, 63%); ¹H NMR (600 MHz, Chloroform-d) δ 7.44 – 7.25 (m, 5H), 4.09 (dd, J = 12.8, 2.4 Hz, 1H), 3.97 (d, J = 2.1 Hz, 1H), 3.84 (dd, J = 12.8, 3.8 Hz, 1H), 3.27 (dt, J = 4.2, 2.4 Hz, 1H), 1.95 (s, 1H); ¹³C{¹H} NMR (101 MHz, Chloroform-d) δ 136.6, 128.5, 128.3, 125.7, 62.3, 61.1, 55.5.

HF•Pyridine (~70% HF-30% pyridine, 75 μL) was added to compound 44 (40 mg, 0.09 mmol) in THF at 0 °C, and the mixture was stirred for 5 mins. The reaction was quenched with saturated aqueous NaHCO₃ and transferred to a separatory funnel. The water layer was extracted with 3 portions of ethyl acetate. The organic layers were collected, pooled, and dried with Na₂SO₄. After concentrating under reduced pressure, the resulting residue was purified by chromatography on silica gel to yield 60 (13 mg, 49%) as a colorless oil.

Compound 60: Purified using a gradient of 0 to 40% EtOAc in hexanes on silica gel; (Colorless oil, 49%); ¹H NMR (400 MHz, Chloroform-d) δ 7.47 – 7.32 (m, 5H), 5.08 (dd, J = 6.3, 2.5 Hz, 1H), 4.53 – 4.42 (m, 1H), 4.00 (dd, J = 12.3, 4.6 Hz, 1H), 3.91 – 3.78 (m, 1H), 2.75-2.5 (bs, 2H). ¹³C{¹H}NMR (101 MHz, Chloroform-d) δ 140.8, 128.6, 128.5, 126.5, 78.5, 65.9, 41.3. IR 2926, 1455, 1002 cm⁻¹. HRMS (ESI) calculated for C₉H₁₁IO₂Na⁺ 300.9702 found 300.9744 (MNa⁺).