Skip to main content
Wiley Open Access Collection logoLink to Wiley Open Access Collection
. 2019 Mar 13;2019(15):2592–2601. doi: 10.1002/ejoc.201900107

Rare‐Earth‐Metal‐Catalyzed Kinetic Resolution of Chiral Aminoalkenes via Hydroamination: The Effect of the Silyl Substituent of the Binaphtholate Ligand on Resolution Efficiency

Hiep N Nguyen 1, Kai C Hultzsch 2,
PMCID: PMC6582503  PMID: 31244549

Abstract

The kinetic resolution of α‐substituted aminopentenes via intramolecular hydroamination was investigated using various 3,3′‐silyl‐substituted binaphtholate yttrium catalysts. High efficiencies in the kinetic resolution were observed for methyl‐, benzyl‐, and phenyl‐substituted substrates utilizing the cyclohexyldiphenylsilyl‐substituted catalyst 2c with resolution factors reaching as high as 90(5) for hex‐5‐en‐2‐amine (3a). Kinetic analysis of the enantioenriched substrates with the matching and mismatching catalyst revealed that the efficiency of catalyst 2c benefits significantly from a favorable Curtin–Hammett pre‐equilibrium and by a large kfast/kslow ratio. Other binaphtholate catalysts were less efficient due to a less favorable Curtin–Hammett pre‐equilibrium, which often favored the mismatching substrate‐catalyst combination. Cyclization of the matched substrate proceeds generally with large trans‐selectivity, whereas the trans/cis‐ratio for mismatched substrates is significantly diminished, favoring the cis‐cyclization product isomer in some instances.

Keywords: Asymmetric catalysis, Hydroamination, Kinetic resolution, Reaction mechanisms, Rare earths

Introduction

Nitrogen‐containing compounds are widely found in nature and biological systems; therefore, this class of organic compounds is of high importance in fundamental research, as well as pharmaceutical and chemical industry1 The metal‐catalyzed hydroamination of olefins, in which an amine N–H functionality adds directly to an unsaturated carbon–carbon bond, provides one of the simplest routes to amine products with 100 % atom efficiency.2 Significant research efforts have resulted in the development of a large variety of catalyst systems for the hydroamination of olefins;3, 4, 5, 6, 7, 8 however, many challenges remain, in particular with respect to asymmetric hydroamination reactions.9, 10, 11

We have developed biphenolate, binaphtholate and NOBIN‐based aminophenolate rare‐earth metal catalysts for the asymmetric intra‐12 and intermolecular[12e], [12f], 13 hydroamination of alkenes. In particular 3,3′‐bis(silyl)‐substituted binaphtholate rare‐earth metal complexes (Figure 1) exhibited high activity and enantioselectivities of up to 96 % ee in intramolecular reactions and up to 66 % ee in intermolecular reactions.[12d], [12f], 13

Figure 1.

Figure 1

Rare‐earth metal complexes based on 3,3′‐bis(silyl)‐binaphtholate ligands for asymmetric hydroamination reactions.

Moreover, complexes 1a and 1b were also applied in the catalytic kinetic resolution of chiral aminoalkenes via the asymmetric hydroamination/cyclization (Scheme 1).[12c], [12d], 14, 15, 16, 17

Scheme 1.

Scheme 1

General scheme of the kinetic resolution of α‐substituted aminoalkenes.

Previously we have shown that resolution factors f as high as 19 can be achieved for a phenyl‐substituted aminopentene using (R)‐1a‐Lu at 40 °C (Scheme 1, R = Ph).[12d], 15 The hydroamination products of aryl‐substituted aminopentenes using the binaphtholate catalysts 1a and 1b displayed high trans/cis diastereoselectivity of up to 50:1. Moreover, the kinetic study of the kinetic resolution process revealed that the Curtin–Hammett pre‐equilibrium favors the matching substrate‐catalyst complex for α‐substituted aminopentenes containing aryl substituents, as indicated by a pre‐equilibrium constant K dias > 1 (vide infra). However, the kinetic resolution of aminoalkene substrates containing aliphatic substituents in the α‐position of the amine was significantly less efficient with these catalysts, primarily as a result of a shifted Curtin–Hammett pre‐equilibrium in favor of the mismatching substrate‐catalyst complex (K dias < 1).

Herein we report the kinetic resolution process using the yttrium catalysts (R)‐2ae[12f] based on binaphtholate ligands with a variety of bulky trisarylsilyl‐, trisalkylsilyl‐, and alkylarylsilyl‐substituents in the 3 and 3′ position (Figure 1). Our previous studies have shown that the sterically demanding silyl groups in the binaphtholate catalysts are responsible for catalyst stability as well as high catalytic activity and selectivity, but herein we will show that subtle changes in these silyl‐substituents can have a significant influence on the kinetic resolution process, especially on the Curtin–Hammett pre‐equilibrium.

Results and Discussion

Previously we had observed that the cyclization of α‐substituted aminopentenes proceeds significantly faster using the triphenylsilyl‐substituted binaphtholate catalyst (R)‐1a‐Y compared to (R)‐1a‐Lu and that (R)‐1a‐Y displayed slightly higher efficiency in the kinetic resolution of the sterically less demanding substrate 3a in comparison to the smaller ionic radius metal complex (R)‐1a‐Lu (Table 1, entries 1, 2).[12c], [12d], 15 We therefore decided to focus our kinetic resolution studies on the more active and presumably more efficient yttrium catalysts (R)‐2ae. A broad range of substrates for intra‐ and intermolecular asymmetric hydroamination reactions unrelated to the kinetic resolution process has been reported for these catalysts recently.[12f] For the purpose of this study we investigated the kinetic resolution of the racemic α‐substituted 1‐aminopent‐4‐enes 3ad (Table 1). These substrates feature aliphatic as well as aromatic substituents which had been kinetically resolved with low (resolution factor f = 2–6 for 3b, 3d) to moderate (f = 6–19 for 3a, 3c) efficiency using catalysts (R)‐1a‐Ln and (R)‐1b‐Ln.[12c], [12d], 15

Table 1.

Catalytic kinetic resolution of α‐substituted 1‐aminopent‐4‐enesa

graphic file with name EJOC-2019-2592-g012.jpg

a

General reaction conditions: 0.10–0.20 mmol substrate ([sub.] = 0.2–0.5 m), 2 mol‐% cat., [D6]benzene, Ar atm.

Trans/cis ratio of products.

Enantiomeric excess of recovered starting material 3ad.

Data from ref.[12d]

Data from ref15

For the sterically least demanding methyl‐substituted aminopentene 3a, the structurally rigid dibenzosilole‐substituted complex (R)‐2a was more efficient than the triphenylsilyl‐substituted binaphtholate catalysts (R)‐1a‐Y and (R)‐1a‐Lu (Table 1, entries 1–3). The sterically more demanding dicyclohexylphenylsilyl‐substituted binaphtholate complex (R)‐2e showed significantly diminished kinetic resolution efficiency (Table 1, entry 5), while exhibiting a significant higher rate of cyclization in comparison to the other catalysts. Remarkably, the cyclohexyldiphenylsilyl‐substituted binaphtholate complex (R)‐2c was significantly more efficient than all other binaphtholate complexes 1 and 2 with a resolution factor f > 5018 for 3a (Table 1, entry 4). Although the silyl groups in the 3 and 3′ positions of the binaphtholate ligands had a pronounced effect on catalytic activity as well as the resolution factors in the cyclization of 3a, the trans/cis diastereoselectivities were rather unaffected, showing consistently low ratios in the range of 7:1 to 9:1.

Higher trans/cis selectivities of up to 20:1 were observed for the benzyl‐substituted aminopentene 3b (Table 1, entries 6–9). However, the cyclization of 3b proceeded at a much lower rate using the tert‐butyldiphenylsilyl‐substituted binaphtholate catalyst (R)‐2b in comparison to (R)‐1a‐Y [42.3 h at 25 °C for (R)‐2b vs. 9 h at 22 °C for (R)‐1a‐Y to obtain 50 % conversion; see Table 1, entries 6 and 8]. This is in contrast to our observation that (R)‐2b generally displayed similar catalytic activity as (R)‐1a‐Y in the cyclization of aminopentenes.[12f] Despite the slow rate of cyclization, (R)‐2b resolved 3b more efficiently than (R)‐1a‐Y. Similar to the previous observation, the resolution of 3b was generally less efficient than the resolution of 3a with the same rare‐earth metal binaphtholate catalyst (for example, compare Table 1, entry 4 and 9). Nevertheless, catalyst (R)‐2c resolved 3b with a still impressive resolution factor of 43.

The kinetic resolution of the phenyl‐substituted aminopentene 3c was performed at 40 °C using catalysts (R)‐2ae with good turnover rates, giving consistently high trans/cis selectivities ≥ 50:1 (Table 1, entries 11–15). Complexes (R)‐2a, (R)‐2b, and (R)‐2c displayed similar catalytic activity in the cyclization of 3c (Table 1, entries 11–13), but as for substrates 3a and 3b, the highest resolution factor (f > 50) was observed for the cyclohexyldiphenylsilyl‐substituted binaphtholate complex (R)‐2c. As expected, the triisopropylsilyl‐substituted binaphtholate catalyst (R)‐2d exhibited the lowest activity as well as the lowest efficiency in the resolution of 3c (Table 1, entry 14) in agreement to its general performance in the hydroamination/cyclization of achiral aminopentenes.[12f] The dicyclohexylphenylsilyl‐substituted complex (R)‐2e exhibited the highest activity in the cyclization of 3c at three times the rate compared to (R)‐2ac (Table 1, entries 11–13 vs. entry 15), but unfortunately at the expense of resolution efficiency.

Previous studies have shown that the sterically more demanding α‐alkyl substrates, such as the benzyl‐substituted 3b and the cyclohexyl‐substituted 3d exhibit significantly diminished resolution factors using the bis(triarylsilyl)‐substituted binaphtholate catalysts (R)‐1a‐Ln and (R)‐1b‐Ln.15 This observation is also true for 3d using the cyclohexyldiphenylsilyl‐substituted binaphtholate catalyst (R)‐2c (Table 1, entry 19). Interestingly, the least reactive, triisopropylsilyl‐substituted catalyst (R)‐2d resolved 3d most effectively among our available binaphtholate catalysts, with a resolution factor of 8.9 (Table 1, entry 20). Among all the tested substrates, cyclization of 3d proceeded with the lowest trans/cis diastereoselectivity in the range of 5:1–10:1.

In order to identify the factors governing the high efficiency of the cyclohexyldiphenylsilyl‐substituted binaphtholate complex (R)‐2c in the kinetic resolution process, we started a more detailed investigation of the kinetic resolution of aminoalkenes using the general model (Scheme 2).[12d], 15, 19

Scheme 2.

Scheme 2

The general model for the kinetic resolution of aminoalkenes ([S], [R] = substrate enantiomers; [cat‐S], [cat‐R] = substrate‐catalyst complex of respective substrate enantiomer).

The two diastereomeric substrate‐catalyst complexes [cat‐S] and [cat‐R] readily interconvert with an equilibrium constant K dias (Equation 1) and each of the complexes reacts with a corresponding rate constant (k R and k S) to give the corresponding hydroamination products. The rate of interconversion between the two substrate‐catalyst complexes is rapid even at low temperatures and significantly higher than both rates of cyclization.[12d]

Kdias=kSRkRS=[catR][S][catS][R] (1)

The resolution factor f is determined by the equilibrium constant K dias and the cyclization rate constants of the two diastereomeric substrate‐catalyst complexes (Equation 2),20 which may be determined independently.

f=KdiaskRkS (2)

For pseudo‐first‐order reactions the resolution factor can be expressed as a function of conversion C and ee of recovered substrate (Equation 3).19

f=ln[(1C)(1ee)]ln[(1C)(1+ee)] (3)

According to Equation 3, the resolution factor f for 3a using the binaphtholate catalyst (R)‐2c can be determined by plotting ln[(1–C)(1 – ee)] vs. ln[(1–C)(1 + ee)] (Figure 2). The relationship between conversion and enantiomeric excess ee is expressed by Figure 3.

Figure 2.

Figure 2

Plot of ln[(1–C)(1 – ee)] vs. ln[(1–C)(1 + ee)] for the kinetic resolution of 3a using binaphtholate catalyst (R)‐2c at 25 °C.

Figure 3.

Figure 3

Dependence of enantiomeric excess of recovered starting material on conversion in the kinetic resolution of 3a with (R)‐2c at 25 °C. The line was fitted to a resolution factor f = 90.

Inspired by the high resolution factor for the methyl‐substituted aminopentene 3a obtained with the cyclohexyldiphenylsilyl‐substituted binaphtholate catalyst (R)‐2c at 25 °C, a large‐scale kinetic resolution of 3a was performed with (S)‐2c, giving (S)‐3a (95 % ee) in 38 % re‐isolated yield at 52 % conversion. The yield of (S)‐3a is lower than expected due to its volatility (b.p. 114–116 °C at 760 Torr). The enantioenriched α‐substituted aminopentenes 3b3d were also prepared using (R)‐2c and the resolution data are summarized in Table 2.

Table 2.

Large‐scale preparation of enantioenriched α‐substituted aminopentenes via kinetic resolution using binaphtholate catalyst 2c a

Subst. Cat. T [°C] t [h] f b Conv. [%] Yield (ee, config.) [%]c
3a (S)‐2c 25 9 90(5) 52 38 (95, S)
3b (R)‐2c 25 22.5 43 57 40 (95, S)
3c (R)‐2c 40 31 > 50 54 40 (97, S)
3d (R)‐2c 25 9.5 5.6(3) 77 18 (95, S)
a

General reaction conditions: 0.8–1.5 g of racemic aminoalkene ([sub.] = 0.9–1.3 m), 2 mol‐% cat., benzene, Ar.

b

Taken from Table 3 (for 3a and 3d) and Table 1 (for 3b and 3c).

c

Isolated yield and ee value of recovered (S)‐3. All recovered aminoalkenes have (S) configuration, because the CIP priorities differ between substrate 3a on the one side and substrate 3bd on the other side. Thus, the (S)‐catalyst enantiomer is the matching catalyst for substrate (R)‐3a, while it is the (R)‐catalyst enantiomer for substrates (R)‐3bd.

The rate constants kfast and kslow for the cyclization of the matching and mismatching substrate‐catalyst combination, respectively, were obtained via kinetic measurements of the cyclization rates of enantioenriched (S)‐3a using (R)‐2c (Figure 4) in the temperature range of 25–50 °C for the faster matching substrate‐catalyst combination, respectively the cyclization of (S)‐3a using (S)‐2c (Figure 5) in the temperature range of 25–55 °C for the slower mismatching substrate‐catalyst combination.

Figure 4.

Figure 4

Time dependence of the substrate concentration in the hydroamination of (S)‐3a using (R)‐2c {matching pair; [(S)‐3a]0 = 0.140 mol L–1, [(R)‐2c] = 2.73 mmol L–1}. The straight lines represent the least square linear regression.

Figure 5.

Figure 5

Time dependence of the substrate concentration in the hydroamination of (S)‐3a using (S)‐2c {mismatching pair; [(S)‐3a]0 = 0.140 mol L–1, [(S)‐2c] = 2.73 mmol L–1}. The straight lines represent the least square linear regression.

The kinetic data and resolution parameters of α‐substituted aminopentenes were determined with the alkylarylsilyl‐substituted binaphtholate catalysts 2b, 2c, and 2e (Table 3). In agreement with the kinetic measurements reported previously for the methyl‐substituted 3a using the triphenylsilyl‐substituted binaphtholate catalyst 1a‐Y,15 the Curtin–Hammett pre‐equilibrium favors the mismatching substrate‐catalyst combination (K dias < 1) when 3a is paired with catalysts 2b and 2e (Table 3, entries 1, 2 and 7). On the contrary, the equilibrium for the cyclohexyldiphenylsilyl‐substituted binaphtholate catalyst 2c and substrate 3a favors the matching substrate‐catalyst complex (K dias > 1); thus, effectively enhancing the efficiency of the kinetic resolution process. The relative rate kfast/kslow remains in the range of 9.1(3)–18.9(2) for the methyl‐substituted aminopentene 3a with our novel binaphtholate catalysts 2b, 2c, and 2e at temperatures ranging from 25 to 50 °C, with the highest ratio being achieved with 2c at 25 °C. Dramatic differences in the trans/cis diastereoselectivities in the cyclization of (S)‐3a using (R)‐2c (Figure 6, trace a, trans/cis = 39:1 for the matching substrate–catalyst pair) and (S)‐3a using (S)‐2c (Figure 6, trace b, trans/cis = 1:1.2 for the mismatching substrate–catalyst pair) account for the low trans/cis selectivities observed in the kinetic resolution of racemic 3a (trans/cis = 7–9:1, Table 1, entries 3–5). Additionally, the trans/cis ratios decrease gradually as the resolution reaction proceeds (Figure 7). It is noteworthy that the reaction of (S)‐3a using (S)‐2c (mismatching substrate–catalyst pair) preferentially produced the cis‐product at all reaction temperatures in the range of 25–50 °C (Table 3, entries 3–6).

Table 3.

Kinetic resolution parameters of α‐substituted aminopentenesa

graphic file with name EJOC-2019-2592-g013.jpg

a

General reaction conditions: 58–74 µmol (S)‐3ad ([sub.] = 0.11–0.14 m), 2 mol‐% cat., [D6]benzene, Ar.

k fast = k R for the reaction of (S)‐3a with (R)‐catalyst; k fast = k S for the reaction of (S)‐3b, (S)‐3c, (S)‐3d with (S)‐catalyst.

Determined from the slope of plot of ln(1–C)(1 – ee) vs. ln(1–C)(1 + ee), with at least three data points.

Conversion for mismatching substrate at which trans/cis ratio was determined.

Data from ref.15

Data from ref.[12d]

Figure 6.

Figure 6

1H NMR spectra of hydroamination products 4a obtained with the matching substrate–catalyst pair (S)‐3a and (R)‐2c (trace a) and with the mismatching substrate–catalyst pair (S)‐3a and (S)‐2c (trace b).

Figure 7.

Figure 7

trans/cis ratio of 4a formed in the kinetic resolution of rac3a using 2 mol‐% of (R)‐2c at 25 °C as a function of conversion. The line is drawn as a guide for the eye.

In agreement to the observations for 3a, the mismatching substrate‐catalyst combination was favored in the Curtin–Hammett pre‐equilibrium in the resolution of the benzyl‐substituted aminopentene 3b with catalyst 2b (Table 3, entry 9). The high efficiency in the kinetic resolution of 3b with 2c was achieved through a combination of high relative rate, kfast/kslow, and a Curtin–Hammett pre‐equilibrium in favor of the matching substrate–catalyst pair (K dias > 1) (Table 3, entry 10). Although the pre‐equilibrium was slightly in favor of the matching substrate–catalyst pair for catalyst 2e, the low kfast/kslow ratio resulted in an overall low efficiency of the kinetic resolution of substrate 3b (Table 3, entry 11). While the diastereoselectivities remained high for the matching pair of substrate (S)‐3b and the (S)‐catalyst, significantly lower trans/cis diastereoselectivities were observed for the mismatching pair with all tested catalysts (Table 3, entries 9–11), in contrast to previous observations for catalyst (S)‐1a‐Y.15

High diastereoselectivities of up to 50:1 were observed for the phenyl‐substituted aminopentene 3c with all binaphtholate catalysts (Table 3, entries 12–16). Although the cyclization rate of the matching substrate–catalyst pair, involving substrate (S)‐3c and catalyst (S)‐1a‐Y, was about three times faster than that of (S)‐3c and (S)‐2c at 60 °C, a higher kfast/kslow ratio was observed for 3c with 2c [kfast/kslow = 15.7(7) vs. 7.1 with 1a‐Y] (Table 3, entries 12 and 14). As a result, the cyclohexyldiphenylsilyl‐substituted binaphtholate catalyst 2c was more efficient in the kinetic resolution of 3c in comparison to 1a‐Y.

The alkylarylsilyl‐substituted binaphtholate catalysts 2b, 2c, and 2e behaved quite differently in the kinetic resolution of the cyclohexyl‐substituted aminopentene 3d compared to the triphenylsilyl‐substituted binaphtholate catalyst 1a‐Y. The kfast/kslow ratios were significantly lower for 2b, 2c, and 2e compared to 1a‐Y; however, this deficiency is overcompensated by a Curtin–Hammett pre‐equilibrium in favor of the matching substrate–catalyst pair for 2b, 2c, and 2e (K dias > 1), whereas in case of 1a‐Y 15 the pre‐equilibrium favors the mismatching substrate–catalyst pair (compare Table 3 entries 18–20 with entry 17). As a result, 2b, 2c, and 2e are slightly more efficient catalysts for the kinetic resolution of 3d in comparison to 1a‐Y.

The Eyring plot for kfast and kslow (Figure 8) provided an access to the activation parameters for the hydroamination/cyclization of (S)‐3a using (R)‐2c (matching substrate–catalyst pair) [ΔH = 43(6) kJ mol–1, ΔS = –137(18) J mol–1 K–1]. Because the reaction of (S)‐3a and (S)‐2c (mismatching substrate–catalyst pair) afforded the products with low trans/cis diastereoselectivities, the activation parameters for each diastereomer were obtained [trans: ΔH = 52(3) kJ mol–1, ΔS = –138(8) J mol–1 K–1; cis: ΔH = 52(5) kJ mol–1, ΔS = –135(16) J mol–1 K–1]. The activation parameters for the matching and mismatching substrate‐catalyst pair seem to be in a similar range to those obtained previously for 3a with catalyst 1a‐Y [matching pair: ΔH = 47.3(3.5) kJ mol–1, ΔS = –128(11) J mol–1 K–1; mismatching pair: ΔH = 54.9(3.1) kJ mol–1, ΔS = –121(9) J mol–1 K–1].15 The negative activation entropy is indicative of a highly organized transition state.[12d], 15, 21

Figure 8.

Figure 8

Eyring plot for the hydroamination/cyclization of (S)‐3a using (R)‐2c (matching pair) and (S)‐2c (mismatching pair).

Stereomodel for the Kinetic Resolution of α‐Substituted Aminopentenes

According to the proposed stereomodel for the kinetic resolution of α‐substituted aminopentenes using binaphtholate rare‐earth metal catalysts, the diastereomers can be obtained via possible cyclization pathways as depicted in Scheme 3.[12d], 15

Scheme 3.

Scheme 3

Proposed stereomodel for the kinetic resolution of α‐substituted aminopentenes with (R)‐binaphtholate yttrium catalysts.[12d], 15 L = aminoalkene substrate or hydroamination product.

The stereomodel for the kinetic resolution is in agreement with the general stereomodel for enantioselective intramolecular hydroamination of aminopentenes by (R)‐binaphtholate rare‐earth metal catalysts, in which the Ln–N bond preferentially approaches the re face of the olefin.[12d] In case of the matching substrate–catalyst pair, the α‐substituent of the aminoalkene rests in an equatorial position of the seven‐membered chair‐like transition state in the conformation that facilitates the approach of the Ln–N bond to the olefin from the re face (Scheme 3, pathway C). In case of the mismatching substrate‐catalyst combination, the sterically unfavorable interaction between the substrate and the alkylarylsilyl‐substituent of the binaphtholate ligand restricts the approach of the Ln–N bond to the olefin from the si face (Scheme 3, pathway A). Pathway B provides an alternative to pathway A, allowing the mismatching substrate‐catalyst complex to avoid the steric interaction between the substrate and the bulky silyl group. However, pathway B requires the α‐substituent of the aminopentene to rest in an axial position, which leads to an unfavorable 1,3‐diaxial interaction in the chair‐like transition state and possibly steric interaction between the α‐substituent R of the substrate and an alkylarylsilyl‐substituent of the binaphtholate ligand, if the α‐substituent R is sufficiently large.

Pathway B accounts for the significantly reduced diastereoselectivities which were observed for the mismatching substrate‐catalyst combinations when using catalysts 2b, 2c, and 2e. Moreover, the cyclization of the mismatching substrate–catalyst pairs (S)‐3a with (S)‐2c, (S)‐3d with (S)‐2b, and (S)‐3d with (S)‐2c generated predominantly the cis‐pyrrolidine products; thus, pathway B becomes the preferred pathway. The exceptionally high efficiency in the kinetic resolution of the methyl‐substituted aminopentene 3a with 2c results from the Curtin–Hammett pre‐equilibrium in favor of the matching substrate‐catalyst complex and a high kfast/kslow ratio.

The large trans/cis diastereoselectivities, exceeding 50:1, observed for the phenyl‐substituted aminopentene 3c in comparison to the alkyl‐substituted aminopentenes 3a, 3b, and 3d, may result from a coordinative interaction of the phenyl‐substituent of 3c with the metal center22 or a π‐interaction of the phenyl‐substituent with a naphthyl ring of the binaphtholate ligand.

Conclusions

The kinetic resolution of α‐substituted aminopentenes via asymmetric hydroamination/cyclization was studied using rare‐earth metal catalysts based on 3,3′‐bis(alkylarylsilyl)‐substituted binaphtholate ligands. In general the cyclohexyldiphenylsilyl‐substituted binaphtholate catalyst (R)‐2c displays high efficiency in the kinetic resolution of the methyl‐, benzyl‐, and phenyl‐substituted substrates 3a, 3b, and 3c, respectively. The highest resolution factor of up to 90(5) was observed for 3a using (R)‐2c. Despite having a favorable Curtin–Hammett pre‐equilbrium, the cyclohexyl‐substituted aminopentene 3d exhibits low efficiency in the kinetic resolution with all binaphtholate catalysts screened in this study as a result of a low kfast/kslow ratio.

The activation parameters for the cyclization of (S)‐3a with complex (R)‐2c (matching substrate–catalyst pair) and (S)‐3a with complex (S)‐2c (mismatching substrate–catalyst pair) are in line with the previously reported data obtained for the cyclization of 3a using complex 1a‐Y.15 It is noteworthy that the mismatching substrate‐catalyst combination of (S)‐3a and (S)‐2c preferentially affords the cis‐product. The kinetic resolution parameters show that high efficiency in the kinetic resolution of the methyl‐substituted 3a with 2c stems from the Curtin–Hammett pre‐equilibrium in favor of the matching substrate‐catalyst combination and a high kfast/kslow ratio.

Experimental Section

General Considerations: All operations were performed under an inert atmosphere of nitrogen or argon using standard Schlenk‐line or glovebox techniques. Solvents and reagents were purified as stated previously.[12d] Complexes 2a2e,[12f] substrates hex‐5‐en‐2‐amine (3a),23 1‐phenylhex‐5‐en‐2‐amine (3b),[12d] 1‐phenylpent‐4‐en‐1‐amine (3c),[12d] and 1‐cyclohexylpent‐4‐en‐1‐amine (3d),15 were prepared according to previously described procedures. The substrates were distilled twice from finely powder CaH2, stored over molecular sieves, and kept in the fridge of a glovebox. (S)‐(+)‐α‐Methoxy‐α‐trifluoro‐methylphenylacetic acid (Mosher acid) was transformed to the corresponding (R)‐Mosher acid chloride using oxalyl chloride/DMF in hexanes.24 Enantiomeric excess for 3a3d was measured by 19F NMR spectroscopy of the corresponding Mosher amides as reported previously.[12d], 15

General Procedure for NMR‐Scale Kinetic Resolution of Chiral α‐Substituted Aminopentenes: In a glove box, a screw cap NMR tube was charged with racemic aminoalkene (20.0 mg, 0.10–0.20 mmol), ferrocene (3.0 mg, 16.1 µmol), [D6]benzene (to give a total volume of 0.5 mL), and catalysts (2.0 mol‐% with respect to racemic aminoalkene, 2.0–4.0 µmol, 0.060 m in [D6]benzene). The NMR tube was capped, immediately removed from the glovebox, and shaken well to dissolve ferrocene. The reaction mixture was heated in a thermostatic oil bath, if required. The conversion was monitored by 1H NMR spectroscopy by following the disappearance of the olefinic signals of the substrate relative to the internal standard ferrocene. The reaction was stopped after ca. 50 % conversion was achieved. The aminoalkene starting material was isolated in form of the hydrochloride salt and enantiomeric excess was determined using the previously reported procedure.[12c], [12d]

General Procedure for Preparation of Chiral α‐Substituted Aminopentenes by Kinetic Resolution: In a glovebox, a 20 mL vial was charged with the racemic aminoalkenes (3c: 0.80 g, 5.0 mmol; 3a, 3b, and 3d: 1.50 g, 8.0–9.0 mmol), benzene (5.0 mL), and 2c (0.5–0.9 mL of solution, 0.20 m in benzene, 0.10–0.18 mmol, 2.0 mol‐%). The vial was kept at 25 °C (3a, 3b, and 3d) or heated to 40 °C (3c). Small aliquots (20 µL) were syringed to NMR tubes, which was then diluted with CDCl3 (0.55 mL), and a 1H NMR spectrum was recorded to monitor the conversion. The reaction was stopped after enantiomeric excess of the starting material reached at least 95 %ee, determined by 19F NMR spectroscopy of its corresponding Mosher amide at 40–65 °C. The chiral α‐substituted aminopentenes were isolated by the standard benzaldimine work‐up procedure[12c], [12d] and were purified by vacuum distillation from CaH2.

(2S)‐Hex‐5‐en‐2‐amine [(S)‐3a]: This compound was prepared by kinetic resolution using (S)‐2c at 25 °C, 52 % conversion after 9 h. The enantioenriched starting material was recovered as colorless oil (38 % yield, bp 114–116 °C at 760 Torr, 95 % ee). The NMR spectra are in agreement with those of rac‐hex‐5‐en‐2‐amine.23

(2S)‐1‐Phenylhex‐5‐en‐2‐amine [(S)‐3b]: This compound was prepared by kinetic resolution using (R)‐2c at 25 °C, 57 % conversion after 22.5 h. The enantioenriched starting material was recovered as colorless oil (40 % yield, 95 % ee, bp 103 °C at 0.2 Torr). The NMR spectra are in agreement with those of rac‐1‐phenylhex‐5‐en‐2‐amine.[12d]

(1S)‐1‐Phenylpent‐4‐en‐1‐amine (3c): This compound was prepared by kinetic resolution using (R)‐2c at 40 °C, 54 % conversion after 31 h. The enantioenriched starting material was recovered as colorless oil (40 % yield, 97 % ee). The NMR spectra are in agreement with those of rac‐1‐phenylpent‐4‐enylamine.[12d]

(1S)‐1‐Cyclohexylpent‐4‐en‐1‐amine [(S)‐3d]: This compound was prepared by kinetic resolution using (R)‐2c at 25 °C, 77 % conversion after 9.5 hours. The enantioenriched starting material was recovered as colorless oil (18 % yield, 95 % ee, bp 80 °C at 0.2 Torr). The NMR spectra are in agreement with those of rac‐1‐cyclohexylpent‐4‐en‐1‐amine.15

General Procedure for Kinetic Catalytic Hydroamination/cyclization Reactions: In a glovebox, a screw cap NMR tube were charged with a solution of the enantioenriched α‐substituted aminopentene (2.0 w% in [D6]benzene, 200–375 µL, 58.0–74.0 µmol), ferrocene (3.0 mg), [D6]benzene (to give a total volume of 500 µL), and catalyst (2.0 mol‐%, 1.16–1.48 µmol, 21–24 µL stock solution in [D6]benzene). The tube was placed in either 400 or 500 MHz NMR thermostatic probe with temperature of 25–55 °C and an arrayed experiment was set up to record 1H NMR spectra automatically in time intervals (30 sec, 1 min, 3 min, 5 min, or 10 min). The conversion was determined based on the disappearance of the olefinic signals of the substrate relative to the internal standard ferrocene. The linear part of the data was fit by least square analysis and kobs was determined from the slope α of a plot of concentration of amine (M) vs. time (min).

Supporting information

Supporting Information

Acknowledgements

This work was supported by the National Science Foundation through an NSF CAREER Award (CHE 0956021).

References

  • 1.a) Ricci A., in: Modern Amination Methods, Wiley‐VCH, 2000; [Google Scholar]; b) Ricci A., in: Amino Group Chemistry: From Synthesis to the Life Sciences, Wiley‐VCH, 2008; [Google Scholar]; c) Chiral Amine Synthesis: Methods, Developments and Applications (Ed.: Nugent T.), Wiley‐VCH: Weinheim, Germany, 2010. [Google Scholar]
  • 2.For general reviews on hydroamination see: a) Müller T. E. and Beller M., Chem. Rev., 1998, 98, 675–704; [DOI] [PubMed] [Google Scholar]; b) Brunet J. J. and Neibecker D. in Catalytic Heterofunctionalization from Hydroamination to Hydrozirconation (Eds.: Togni A. and Grützmacher H.), Wiley‐VCH, Weinheim, 2001, pp. 91–141; [Google Scholar]; c) Müller T. E., Hultzsch K. C., Yus M., Foubelo F. and Tada M., Chem. Rev., 2008, 108, 3795–3892; [DOI] [PubMed] [Google Scholar]; d) Doye S. in Science of Synthesis, Vol. 40a (Ed.: Enders D.), Thieme, Stuttgart, 2009, pp. 241–304; [Google Scholar]; e) Reznichenko A. L. and Hultzsch K. C., Top. Organomet. Chem., 2013, 43, 51–114; [Google Scholar]; f) Nishina N. and Yamamoto Y., Top. Organomet. Chem., 2013, 43, 115–143; [Google Scholar]; g) Reznichenko A. L. and Hultzsch K. C. in Organic Reactions, Vol. 88 (Eds.: Denmark S. E. and Charette A.), Wiley: Hoboken, NJ, 2016, pp. 1–554. [Google Scholar]
  • 3.Reviews on rare‐earth‐metal‐catalyzed hydroaminations: a) Hong S. and Marks T. J., Acc. Chem. Res., 2004, 37, 673–686; [DOI] [PubMed] [Google Scholar]; b) Reznichenko A. L. and Hultzsch K. C., Struct. Bonding (Berlin), 2010, 137, 1–48; [Google Scholar]; c) Trifonov A. A., Basalov I. V. and Kissel A. A., Dalton Trans., 2016, 45, 19172–19193. [DOI] [PubMed] [Google Scholar]
  • 4.Reviews on Group 4‐ and actinide‐catalyzed hydroaminations: a) Bytschkov I. and Doye S., Eur. J. Org. Chem., 2003, 935–946; [Google Scholar]; b) Pohlki F. and Doye S., Chem. Soc. Rev., 2003, 32, 104–114; [DOI] [PubMed] [Google Scholar]; c) Doye S., Synlett, 2004, 1653–1672; [Google Scholar]; d) Odom A. L., Dalton Trans., 2005, 225–233; [DOI] [PubMed] [Google Scholar]; e) Severin R. and Doye S., Chem. Soc. Rev., 2007, 36, 1407–1420; [DOI] [PubMed] [Google Scholar]; f) Lee A. V. and Schafer L. L., Eur. J. Org. Chem., 2007, 2243–2255; [Google Scholar]; g) Eisenberger P. and Schafer L. L., Pure Appl. Chem., 2010, 82, 1503–1515; [Google Scholar]; h) Andreas T. and Eisen M. S., Chem. Soc. Rev., 2008, 37, 550–567. [DOI] [PubMed] [Google Scholar]
  • 5.Reviews on alkali‐ and alkaline‐earth‐metal‐catalyzed hydroaminations: a) Seayad J., Tillack A., Hartung C. G. and Beller M., Adv. Synth. Catal., 2002, 344, 795–813; [Google Scholar]; b) Harder S., Chem. Rev., 2010, 110, 3852–3876; [DOI] [PubMed] [Google Scholar]; c) Barrett A. G. M., Crimmin M. R., Hill M. S. and Procopiou P. A., Proc. R. Soc. London Ser. A, 2010, 466, 927–963; [Google Scholar]; d) Crimmin M. R. and Hill M. S., Top. Organomet. Chem., 2013, 45, 191–241. [Google Scholar]
  • 6.Reviews on late transition metal‐based catalysts: a) Beller M., Breindl C., Eichberger M., Hartung C. G., Seayad J., Thiel O. R., Tillack A. and Trauthwein H., Synlett, 2002, 1579–1594; [Google Scholar]; b) Hartwig J. F., Pure Appl. Chem., 2004, 76, 507–516; [Google Scholar]; c) Widenhoefer R. A. and Han X., Eur. J. Org. Chem., 2006, 4555–4563; [Google Scholar]; d) Brunet J. J., Chu N. C. and Rodriguez‐Zubiri M., Eur. J. Org. Chem., 2007, 4711–4722; [Google Scholar]; e) Hesp K. D. and Stradiotto M., ChemCatChem, 2010, 2, 1192–1207; [Google Scholar]; f) Jenter J., Lühl A., Roesky P. W. and Blechert S., J. Organomet. Chem., 2010, 695, 406–418; [Google Scholar]; g) Rodriguez‐Ruiz V., Carlino R., Bezzenine‐Lafollee S., Gil R., Prim D., Schulz E. and Hannedouche J., Dalton Trans., 2015, 44, 12029–12059; [DOI] [PubMed] [Google Scholar]; h) Huang L., Arndt M., Gooßen K., Heydt H. and Gooßen L. J., Chem. Rev., 2015, 115, 2596–2697 [DOI] [PubMed] [Google Scholar]; For a recent example of an iron‐catalyzed hydroamination of aminoalkenes, see: i) Lepori C., Bernoud E., Guillot R., Tobisch S. and Hannedouche J., Chem. Eur. J., 2019, 25, 835–844. [DOI] [PubMed] [Google Scholar]
  • 7.For reviews on photocatalytic hydroaminations see: a) Margrey K. A. and Nicewicz D. A., Acc. Chem. Res., 2016, 49, 1997–2006; [DOI] [PubMed] [Google Scholar]; b) Menigaux D., Belmont P. and Brachet E., Eur. J. Org. Chem., 2017, 2008–2055. [Google Scholar]
  • 8.For a review on the asymmetric formal hydroamination of alkenes using copper hydride catalysts see: a) Pirnot M. T., Wang Y. M. and Buchwald S. L., Angew. Chem. Int. Ed., 2016, 55, 48–57; [DOI] [PMC free article] [PubMed] [Google Scholar]; Angew. Chem., 2016, 128, 48–57 [Google Scholar]; For a review on the Cope‐type hydroamination see: b) Beauchemin A. M., Org. Biomol. Chem., 2013, 11, 7039–7050. [DOI] [PubMed] [Google Scholar]
  • 9.For reviews on asymmetric hydroamination see: a) Roesky P. W. and Müller T. E., Angew. Chem. Int. Ed., 2003, 42, 2708–2710; [DOI] [PubMed] [Google Scholar]; Angew. Chem., 2003, 115, 2812–2814 [Google Scholar]; b) Hultzsch K. C., Adv. Synth. Catal., 2005, 347, 367–391; [Google Scholar]; c) Aillaud I., Collin J., Hannedouche J. and Schulz E., Dalton Trans., 2007, 5105–5118; [DOI] [PubMed] [Google Scholar]; d) Zi G., Dalton Trans., 2009, 9101–9109; [DOI] [PubMed] [Google Scholar]; e) Chemler S. R., Org. Biomol. Chem., 2009, 7, 3009–3019; [DOI] [PMC free article] [PubMed] [Google Scholar]; f) Zi G., J. Organomet. Chem., 2011, 696, 68–75; [Google Scholar]; g) Hannedouche J., Collin J., Trifonov A. and Schulz E., J. Organomet. Chem., 2011, 696, 255–262; [Google Scholar]; h) Hannedouche J. and Schulz E., Chem. Eur. J., 2013, 19, 4972–4985; [DOI] [PubMed] [Google Scholar]; i) Reznichenko A. L., Nawara‐Hultzsch A. J. and Hultzsch K. C., Top. Curr. Chem., 2013, 343, 191–260; [DOI] [PubMed] [Google Scholar]; j) Michon C., Abadie M. A., Medina F. and Agbossou‐Niedercorn F., J. Organomet. Chem., 2017, 847, 13–27. [Google Scholar]
  • 10.For selected examples of highly enantioselective intramolecular hydroamination of aminoalkenes see: a) Wood M. C., Leitch D. C., Yeung C. S., Kozak J. A. and Schafer L. L., Angew. Chem. Int. Ed., 2007, 46, 354–358; [DOI] [PubMed] [Google Scholar]; Angew. Chem., 2007, 119, 358–362 [Google Scholar]; b) Shen X. and Buchwald S. L., Angew. Chem. Int. Ed., 2010, 49, 564–567; [DOI] [PMC free article] [PubMed] [Google Scholar]; Angew. Chem., 2010, 122, 574–577 [Google Scholar]; c) Manna K., Kruse M. L. and Sadow A. D., ACS Catal., 2011, 1, 1637–1642; [Google Scholar]; d) Zhang Y., Yao W., Li H. and Mu Y., Organometallics, 2012, 31, 4670–4679; [Google Scholar]; e) Zhang X., Emge T. J. and Hultzsch K. C., Angew. Chem. Int. Ed., 2012, 51, 394–398; [DOI] [PubMed] [Google Scholar]; Angew. Chem., 2012, 124, 406–410 [Google Scholar]; f) Manna K., Everett W. C., Schoendorff G., Ellern A., Windus T. L. and Sadow A. D., J. Am. Chem. Soc., 2013, 135, 7235–7250; [DOI] [PubMed] [Google Scholar]; g) Chai Z., Hua D., Li K., Chu J. and Yang G., Chem. Commun., 2014, 50, 177–179; [DOI] [PubMed] [Google Scholar]; h) Hussein L., Purkait N., Biyikal M., Tausch E. and Roesky P. W., Chem. Commun., 2014, 50, 3862–3864; [DOI] [PubMed] [Google Scholar]; i) Zhou X., Wei B., Sun X. L., Tang Y. and Xie Z., Chem. Commun., 2015, 51, 5751–5753 [DOI] [PubMed] [Google Scholar]; For the highly enantioselective intermolecular hydroamination of cyclopropenes see: j) Teng H. L., Luo Y., Wang B., Zhang L., Nishiura M. and Hou Z., Angew. Chem. Int. Ed., 2016, 55, 15406–15410; [DOI] [PubMed] [Google Scholar]; Angew. Chem., 2016, 128, 15632–15636. [Google Scholar]
  • 11.For selected examples of highly enantioselective intramolecular hydroamination reactions of aminodienes and aminoallenes see: a) LaLonde R. L., Sherry B. D., Kang E. J. and Toste F. D., J. Am. Chem. Soc., 2007, 129, 2452–2453; [DOI] [PubMed] [Google Scholar]; b) Hamilton G. L., Kang E. J., Mba M. and Toste F. D., Science, 2007, 317, 496–499; [DOI] [PubMed] [Google Scholar]; c) Zhang Z., Bender C. F. and Widenhoefer R. A., Org. Lett., 2007, 9, 2887–2889; [DOI] [PubMed] [Google Scholar]; d) LaLonde R. L., Wang Z. J., Mba M., Lackner A. D. and Toste F. D., Angew. Chem. Int. Ed., 2010, 49, 598–601; [DOI] [PMC free article] [PubMed] [Google Scholar]; Angew. Chem., 2010, 122, 608–611 [Google Scholar]; e) Shapiro N. D., Rauniyar V., Hamilton G. L., Wu J. and Toste F. D., Nature, 2011, 470, 245–249; [DOI] [PMC free article] [PubMed] [Google Scholar]; f) Kanno O., Kuriyama W., Wang Z. J. and Toste F. D., Angew. Chem. Int. Ed., 2011, 50, 9919–9922; [DOI] [PMC free article] [PubMed] [Google Scholar]; Angew. Chem., 2011, 123, 10093–10096. [Google Scholar]
  • 12.a) Gribkov D. V., Hultzsch K. C. and Hampel F., Chem. Eur. J., 2003, 9, 4796–4810; [DOI] [PubMed] [Google Scholar]; b) Gribkov D. V., Hampel F. and Hultzsch K. C., Eur. J. Org. Chem., 2004, 4091–4101; [Google Scholar]; c) Gribkov D. V. and Hultzsch K. C., Chem. Commun., 2004, 730–731; [DOI] [PubMed] [Google Scholar]; d) Gribkov D. V., Hultzsch K. C. and Hampel F., J. Am. Chem. Soc., 2006, 128, 3748–3759; [DOI] [PubMed] [Google Scholar]; e) Reznichenko A. L. and Hultzsch K. C., Organometallics, 2013, 32, 1394–1408; [Google Scholar]; f) Nguyen H. N., Lee H., Audörsch S., Reznichenko A. L., Nawara‐Hultzsch A. J., Schmidt B. and Hultzsch K. C., Organometallics, 2018, 37, 4358–4379; [Google Scholar]; g) Yu X. and Marks T. J., Organometallics, 2007, 26, 365–376. [Google Scholar]
  • 13. Reznichenko A. L., Nguyen H. N. and Hultzsch K. C., Angew. Chem. Int. Ed., 2010, 49, 8984–8987; [DOI] [PubMed] [Google Scholar]; Angew. Chem., 2010, 122, 9168–9171. [Google Scholar]
  • 14.For reviews on kinetic resolution see: a) Kagan H. B. and Fiaud J. C., Top. Stereochem., 1988, 18, 249–330; [Google Scholar]; b) Vedejs E. and Jure M., Angew. Chem. Int. Ed., 2005, 44, 3974–4001; [DOI] [PubMed] [Google Scholar]; Angew. Chem., 2005, 117, 4040–4069 [Google Scholar]; c) Pellissier H., Adv. Synth. Catal., 2011, 353, 1633–1666. [Google Scholar]
  • 15. Reznichenko A. L., Hampel F. and Hultzsch K. C., Chem. Eur. J., 2009, 15, 12819–12827 [DOI] [PubMed] [Google Scholar]; For the application of NOBIN‐based aminophenolate complexes in the kinetic resolution of aminoalkenes see ref.[12e].
  • 16.For the gold‐catalyzed dynamic kinetic resolution of aminoallenes via hydroamination/cyclization see: a) Zhang Z., Bender C. F. and Widenhoefer R. A., J. Am. Chem. Soc., 2007, 129, 14148–14149; [DOI] [PubMed] [Google Scholar]; For the stereoconvergent, intermolecular asymmetric hydroamination of racemic allenes see: b) Butler K. L., Tragni M. and Widenhoefer R. A., Angew. Chem. Int. Ed., 2012, 51, 5175–5178; [DOI] [PMC free article] [PubMed] [Google Scholar]; Angew. Chem., 2012, 124, 5265–5268 [Google Scholar]; For the desymmetrization of aminodialkenes and aminodialkynes see: c) Manna K., Eedugurala N. and Sadow A. D., J. Am. Chem. Soc., 2015, 137, 425–435; [DOI] [PubMed] [Google Scholar]; For the diastereodivergent asymmetric carboamination/annulation of cyclopropenes with aminoalkenes see: d) Teng H. L., Luo Y., Nishiura M. and Hou Z., J. Am. Chem. Soc., 2017, 139, 16506–16509. [DOI] [PubMed] [Google Scholar]
  • 17.For rare‐earth‐metal‐catalyzed kinetic resolution processes other than hydroamination, see for example: a) Lin M.‐H. and RajanBabu T. V., Org. Lett., 2002, 4, 1607–1610; [DOI] [PubMed] [Google Scholar]; b) Maxwell C. I., Shah K., Samuleev P. V., Neverov A. A. and Brown R. S., Org. Biomol. Chem., 2008, 6, 2796–2803; [DOI] [PubMed] [Google Scholar]; c) Zhou L., Liu X., Ji J., Zhang Y., Hu X., Lin L. and Feng X., J. Am. Chem. Soc., 2012, 134, 17023–17026; [DOI] [PubMed] [Google Scholar]; d) Zhou L., Liu X., Ji J., Zhang Y., Wu W., Liu Y., Lin L. and Feng X., Org. Lett., 2014, 16, 3938–3941; [DOI] [PubMed] [Google Scholar]; e) Zhang Y., Liu X., Zhou L., Wu W., Huang T., Liao Y., Lin L. and Feng X., Chem. Eur. J., 2014, 20, 15884–15890; [DOI] [PubMed] [Google Scholar]; f) Wu B., Gallucci J. C., Parquette J. R. and RajanBabu T. V., Chem. Sci., 2014, 5, 1102–1117; [Google Scholar]; g) Xu Y., Kaneko K., Kanai M., Shibasaki M. and Matsunaga S., J. Am. Chem. Soc., 2014, 136, 9190–9194; [DOI] [PubMed] [Google Scholar]; h) Huang T., Lin L., Hu X., Zheng J., Liu X. and Feng X., Chem. Commun., 2015, 51, 11374–11377; [DOI] [PubMed] [Google Scholar]; i) Li N. and Guan B. T., Adv. Synth. Catal., 2017, 359, 3526–3531; [Google Scholar]; j) Kisan H. K. and Sunoj R. B., ACS Catal., 2018, 8, 7633–7644. [Google Scholar]
  • 18.Resolution factors > 50 are difficult to determine with sufficient precision based on a single data point. A better estimate for these large f values can be obtained from linear regression of several data points (vide infra).
  • 19.For the detailed derivation of the underlying equations see ref.[12d].
  • 20.For simplification we assume that kR/kS represents kfast/kslow for all substrates. Note however, that for substrate 3a the S enantiomer is the faster reacting enantiomer when using the (R)‐binaphtholate catalysts.
  • 21. Gagné M. R., Stern C. L. and Marks T. J., J. Am. Chem. Soc., 1992, 114, 275–294. [Google Scholar]
  • 22. Bochkarev M. N., Chem. Rev., 2002, 102, 2089–2117. [DOI] [PubMed] [Google Scholar]
  • 23. Kim J. Y. and Livinghouse T., Org. Lett., 2005, 7, 4391–4393. [DOI] [PubMed] [Google Scholar]
  • 24. Smith P. M. and Thomas E. J., J. Chem. Soc., Perkin Trans. 1, 1998, 3541–3556. [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supporting Information


Articles from European Journal of Organic Chemistry are provided here courtesy of Wiley

RESOURCES