Addition of chiral and achiral allyltrichlorostannanes to chiral±-alkoxy aldehydes

Abstracts

Achiral and chiral allyltrichlorostannanes reacted with chiral ±-alkoxy aldehydes to give the corresponding homoallylic alcohols with moderate to good levels of 1,4-syn-diastereoselection.

allyltrichlorostannanes; allylsilanes; homoallylic alcohols

Aliltricloroestananas quirais e aquirais reagem com ±-alcóxi aldeídos quirais para fornecer alcoóis homoalílicos com moderados a bons níveis de diastereosseletividade 1,4-syn.

SHORT REPORT

Addition of chiral and achiral allyltrichlorostannanes to chiralα-alkoxy aldehydes

Luiz C. Dias^*; Tatiana Augusto; Carla C. Perez and Leonardo J. Steil

Chemistry Institute, State University of Campinas, UNICAMP, P.O. Box 6154, 13083-970 Campinas-SP, Brazil

ABSTRACT

Achiral and chiral allyltrichlorostannanes reacted with chiral α-alkoxy aldehydes to give the corresponding homoallylic alcohols with moderate to good levels of 1,4-syn-diastereoselection.

Keywords: allyltrichlorostannanes, allylsilanes, homoallylic alcohols

RESUMO

Aliltricloroestananas quirais e aquirais reagem com α-alcóxi aldeídos quirais para fornecer alcoóis homoalílicos com moderados a bons níveis de diastereosseletividade 1,4-syn.

Introduction

Allylsilanes and allylstannanes are among the most important groups of organometallic-type reagents available for the control of acyclic stereochemistry and their reaction with aldehydes in the presence of Lewis acids is an important procedure for the preparation of homoallylic alcohols.^1,2 The addition of allylstannanes bearing a stereogenic center to chiral aldehydes is particularly interesting in organic synthesis. We recently communicated that in situprepared chiral allyltrichlorostannanes react with chiral aldehydes to give 1,4-synhomoallylic alcohols with high levels of diastereoselectivity.^3-11

We wish to describe here a stereocontrolled reaction between achiral and chiral allyltrichlorostannanes with chiral lactate-derived aldehydes to give fragments which can be found in a large variety of naturally-occurring products with promising biological activities.¹² This study details our efforts to understand the double stereodifferentiating stereocontrol elements involved in chiral allyltrichlorostannane additions to chiral aldehydes.¹³

Results and Discussion

Achiral and chiral allylsilanes 1-4were prepared from the corresponding easily available methyl esters, as described in previous papers from this laboratory (Scheme 1).^3-11,14 According to previously established experimental procedures, the allylsilanes were mixed with SnCl₄ (1.0 equiv. in CH₂Cl₂) before the addition of a solution of the aldehyde in order to promote the SiMe₃/SnCl₃ exchange leading to the corresponding allyltrichlorostannanes 5-8(Scheme 1).⁵

To the best of our knowledge, the first spectroscopic information available on exchange reactions involving allylsilanes and SnCl₄ was reported by Denmark and co-workers in 1988.¹³ In 1999, we described the first direct evidence for interaction between SnCl₄ and chiral allylic silane 3bearing an ether functionality that generated a new species by means of NMR spectroscopy.⁵ In a continuation of these initial studies we have done a spectroscopic study (¹H and ¹¹⁹Sn NMR) of the reactions of allylsilanes 1-4(0.15 molL^-1 solution in CDCl₃) with SnCl₄ leading to the corresponding allyltrichlorostannanes 5-8, respectively (Scheme 1).

For allyltrimethylsilane 1the SiMe₃/SnCl₃ exchange producing allyltrichlorostannane 5and Me₃SiCl is complete after 2 h at room temperature (Scheme 1).⁵ For allylsilane 2the SiMe₃/SnCl₃ exchange to give 6and Me₃SiCl is faster, as expected for a 1,1-disubstituted electron-rich olefin, being complete after 10 minutes at room temperature.¹⁴ Upon addition of SnCl₄ to a solution of allylsilanes (R)-3and (S)-4in CDCl₃, at -60 ºC, slightly yellow homogeneous solutions were obtained. The resulting NMR spectrum at -60 ^oC showed formation of Me₃SiCl and complete consumption of both allylsilanes within less than 1 minute to give allyltrichlorostannanes (R)-7and (S)-8, respectively. It appears that the oxygen functionality is responsible for the rapid SiMe₃/SnCl₃ exchange reaction observed even at low temperatures for these particular allylsilanes and SnCl₄. The SiMe₃/SnCl₃ exchange is probably facilitated by coordination of tin to this oxygen followed by cleavage of the carbon-silicon bond by a free chloride ion.

Analysis of the corresponding ¹H NMR spectrum showed a deshielding for hydrogens H₁ to H₄ in allylstannane 5 when compared to the same signals for allylsilane 1 (Table 1).⁵

The same trend is observed for allylstannane6when compared to allylsilane 2 (Table 2).¹⁴

In the case of (R)-7, the deshielding of the hydrogens H₆ to H₉ in the ¹H NMR spectrum provides the best diagnostics (Table 3). The methylenic hydrogens H₆ and H₇ as well as the benzylic hydrogens H₈ and H₉ are too far away from the trichlorotin group to suffer from inductive effects. We believe that the deshielding observed for these hydrogens in (R)-7is due to the internal coordination of this oxygen to tin, as proposed in Table 3.⁵

A similar behavior is observed for allylstannane (S)-8when compared to allylsilane (S)-4 (Table 4).

In addition, we have observed ¹¹⁹Sn resonance signals at -28 ppm for allylstannane 5(Figure 1).⁵ The tin chemical shift for allylstannane (R)-7appeared at -187 ppm and for allylstannane (S)-8appeared at -169 ppm. The tin chemical shift for complexes 9and 10are -301 ppm and -599 ppm, respectively, while for free SnCl₄ it is -156 ppm. We believe that tin chemical shifts are highly sensitive to oxygen bonding, as observed for 9and 10, and the tin chemical shifts observed for (R)-7and (S)-8are strong evidence in favor of the proposed complexed intermediates.

The corresponding chiral aldehydes 11and 12were prepared in excellent yields from methyl lactate (Figure 2).^15,16 These substrates have been selected to be representative of the complex fragments that might be coupled in polyacetate and polypropionate-derived aldol-type reactions. For aldehydes 11, internal chelation is presumably prevented since, with few exceptions, silyl ethers are generally recognized for their poor coordinating and chelating abilities.¹⁷

In order to check the facial selectivities of aldehydes 11and12, we reacted them with achiral allyltrichlorostannanes 5and 6. Achiral allyltrichlorostannane 5reacted with chiral α-alkoxy aldehyde (S)-11in CH₂Cl₂ at -78 ºC to give the corresponding 1,2-synproduct 13 (anti-Felkin isomer) as the major isomer in 45% yield for the two-step sequence (preparation of the aldehyde from the ester and coupling reaction), with 60:40 diastereoselectivity (Scheme 2).^18,19 Achiral allyltrichlorostannane 6addition to the same aldehyde gave the corresponding 1,2-synproduct 15as the major isomer in 40% yield for the two-step sequence, again with 60:40 diastereoselectivity (Scheme 2). The stereoinduction observed in these reactions indicates that the intrinsic facial bias imposed by the resident α-OTBS substituent results in preferential formation of the 1,2-syndiastereomer, with a small preference for the anti-Felkin type approach.¹⁹ One might project that the transition states of these reactions exhibit less charge separation than the aldol processes and are, accordingly, less subject to the electrostatic influence of the α-OTBS function.

The relative stereochemistry for the major product 13was confirmed by comparison with data described in the literature.²⁰ In addition, we have also confirmed the relative stereochemistry for both 13and 15by analysis of the ¹H and ¹³C NMR chemical shifts for both synand antiisomers, as described by Heathcock²¹ and Hoffmann²² for similar structures and applied to more complex substrates in this work. ¹H NMR and ¹³C NMR spectroscopy are very useful tools to study substituent effects on the electronic environment of a given carbon, as well as to determine the relative stereochemistry in acyclic molecules, especially by analysis of the coupling constants (J) in the corresponding ¹H NMR spectra. In the case of homoallylic alcohols 13-16, it is possible to assign the relative stereochemistry by ¹H and ¹³C NMR analysis, as these compounds, by adopting an internal hydrogen-bonded conformation, exhibit magnetically distinct NMR environments.

The intramolecular hydrogen bond leads to a 5-member ring in which the substituents are trans (13and 15) or cis(14and 16) and the predominance of hydrogen-bonded conformations should be reflected in different ¹H and ¹³C chemical shifts (Table 5). In fact, very strong experimental evidence for the existence of intramolecular hydrogen bonds in alcohols 13-16comes from the observed chemical shifts in the ¹H NMR and ¹³C NMR spectra measured in CDCl₃ (Table 5). We have shown previously that the intrinsic low basicity of silyl ethers does not affect the capacity of the oxygen attached to the silicon atom to form intramolecular hydrogen bonds.²³ The ¹H NMR spectra for compounds 13-16are first order and the coupling constants (J) and chemical shifts (δ) are directly measured from the spectra. The ¹H NMR chemical shifts of H _a and H_b for both 1,2-synisomers 13and 15are more shielded than the corresponding signals for H_a and H_b in 1,2-antihomoallylic alcohols 14and 16. For alcohol 13(R = TBS), the ¹H chemical shifts are 3.38 (Ha) and 3.70 (Hb), showing a transorientation between these two hydrogens. For alcohol 14, the ¹H chemical shifts are 3.56 (Ha) and 3.78 (Hb), showing a cisorientation between these two hydrogens. The same trend is observed for synand antihomoallylic alcohols 15 and 16.

In addition, the ¹³C chemical shifts for the methyl group in syncompounds 13and 15are more deshielded when compared to the ¹³C chemical shifts in 14 and 16.

We next examined the stereochemical impact of a benzyl-protecting group at the oxygen in position α to the carbonyl aldehyde. Before starting the study described in Scheme 3, we expected that under conditions favouring internal chelation, the carbonyl facial bias of aldehyde (S)12should be highly predictable. In fact, that proved to be the case. The facial bias of aldehyde (S)-12was determined after reaction with allyltrichlorostannane 5in CH₂Cl₂ at -78 ºC to give a 97:3 mixture of diastereoisomers 17and 18, in 45% yield over the two step sequence (Scheme 3).

This benzyl-protecting group imposes an intrinsic facial bias on the carbonyl that results in the formation of the 1,2-syn-dioxygen relationship. This leads to higher levels of diastereoselection when compared to the use of a TBS protecting group.

The 1,2-synrelative stereochemistry for adduct 17was confirmed by comparison of ¹H- and ¹³C NMR data as well as its optical rotation with literature values.²⁴

Previous work from our laboratory showed that allyltrichlorostannane (R)-7reacted with achiral aldehydes leading to the formation of 1,4-synproducts as the major isomers (up to > 95:5 diastereoselectivity).^3-11

At this point we initiated the double stereodifferentiating studies involving allyltrichlorostannane (R)-7and chiral aldehydes 11and 12. Addition of allyltrichlorostannane (R)-7to aldehyde (S)-11in CH₂Cl₂ at -78 ºC gave an 85:15 mixture of diastereoisomers 19and 20, (Scheme 4).

Allyltrichlorostannane (R)-7reacted with aldehyde (R)-11to give 1,4-syn-1,2-synproduct 21as the major product in 55% yield (2 steps), although with only 70:30 diastereoselectivity (Scheme 4).

The facial bias of this chiral allyltrichlorostannane is dominated by the α-methyl stereocenter and tends to give the 1,4-synisomer with Si-face attack, but the facial bias of this particular aldehyde is to give the 1,2-synproduct. We were surprised with the result with aldehyde (R)-11as we were expecting a higher level of diastereoselection in favor of the product 21.

The relative stereochemistry for the major products was determined after conversion to the corresponding dimethylacetonides (Scheme 5). Treatment of a mixture of 19and 20with TBAF in THF at room temperature gave diols 23and 24(67% yield), which was followed by reaction with 2,2-dimethoxypropane and catalytic amounts of camphorsulphonic acid (CSA) to give acetonides 25and 26in 40% yield after purification by flash column chromatography (Scheme 5).

The cis-acetonide 25comes from the 1,2-antiisomer 19and the trans- acetonide 26originates from the corresponding 1,2-synisomer 20. The dimethyl groups (Me_a and Me_b) in both transand cisdimethylacetonides are in different (average) chemical environments, giving rise to characteristic signals. As observed by Lombardo and coworkers²⁵ the difference in chemical shifts of the methyl groups (Me_a and Me_b) in the five member ring of the dimethylacetonides is larger for the cisisomer (0.12-0.14 ppm) when compared to the transisomer (0.01-0.04 ppm).²⁵ In Figure 3 we can observe the partial ¹H NMR for cis and trans acetonides 25 and 26 .

There is a larger difference in chemical shifts for the methyl groups (Me_a and Me_b) in the cisisomer (Δδ = 0.12 ppm) when compared to the chemical shifts for the same methyl groups of the transisomer (Δδ = 0.05 ppm). Based on this result we conclude that the 1,2-antiisomer 19is the major product.²⁶

The relative stereochemistry for compounds 21and 22was determined based on the same strategy (Scheme 6).

As before, we observed that the most intense signals come from the trans-acetonide 30, which in this case originates from the 1,2-syn adduct 21 (Figure 4).

We next moved to investigate the addition of allyltrichlorostannane (R)-7to enantiomeric aldehydes 12(Scheme 7). Allyltrichlorostannane (R)-7reacted with chiral α-benzyloxy-aldehyde (S)-12in CH₂Cl₂ at -78 ºC to give the corresponding 1,2-antiproduct 31as the major product in 70% yield and with 85:15 diastereoselectivity (Scheme 7). The coupling reaction between allyltrichlorostannane (R)-7and aldehyde (R)-12in CH₂Cl₂ at -78 ºC gave a 63:37 mixture of diastereoisomers 33and 34, in 60% yield for the two-step sequence.

It is interesting to point out that as the facial bias of this aldehyde is to give the 1,2-synproducts, we expected a matchedcase and much higher levels of diastereoselectivity in the reaction of (R)-7with (R)-12. Again, we were surprised to see that this was not the case.

The relative stereochemistries for both 31and 33were determined by applying the same methodology based on the ¹³C NMR chemical shifts described before for 13-16(Table 5). The 1,2-antiisomer is the major product as we can observe from the ¹³C NMR chemical shifts for the more shielded Me_c (Figure 5). In the case of 31and 32, the ¹³C chemical shifts for Me_c in 31appears more shielded (14.8 ppm) when compared to 32 (15.5 ppm).

In the case of 33and 34, we were able to confirm that the 1,2-synis the major product, based on the ¹³C chemical shifts for Me_c in 33 (15.5 ppm) and 34 (14.5 ppm).

At this point, we turned our attention to the coupling reactions involving allyltrichlorostannane (S)-8. Addition of allyltrichlorostannane (S)-8to aldehyde (S)-11gave a 65:35 mixture of diastereoisomers 35and 36in 60% yield (2 steps) (Scheme 8).

We next examined the addition of the same allylstannane to the enantiomeric aldehyde (R)-11affording a 75:25 mixture of isomers 37and 38in 47% yield for the two-step sequence.

Again, these reactions with α-OTBS aldehydes are characterized by poor levels of diastereoselectivity.

The relative stereochemistry for the major products was again determined based on the analysis of the ¹³C NMR chemical shifts of the corresponding 5-membered dimethylacetonides (Scheme 9). Treatment of 35and 36with TBAF at rt followed by treatment of the corresponding diols under acidic conditions with 2,2-dimethoxypropane gave acetonides 41 and 42, respectively.

The ¹H NMR methyl resonances observed at 1.34 and 1.46 for 41are characteristic of a cis-acetonide and ¹H NMR methyl resonances at 1.38 and 1.40 for 42are consistent with a trans-acetonide (Figure 6).²⁵

The same strategy was applied to 37and 38, providing acetonides 45 and 46 (Scheme 10).

As can be seen from Figure 7, the trans-acetonide, which comes from the 1,2-synadduct is the major isomer observed in this reaction.

Addition of allyltrichlorostannane (S)-8to aldehyde (S)-12at -78 ºC in CH₂Cl₂, gave an 80:20 diastereoisomeric mixture in favor of the 1,2-antiisomer 47in 70% yield for the 2 steps (Scheme 11).Addition of allyltrichlorostannane (S)-8to aldehyde (R)-12at -78 ºC in CH₂Cl₂, led to a 60:40 diastereoisomeric mixture favoring the 1,2-synisomer in 60% yield for the 2 steps (Scheme 11).

The selectivity in the latter case was somewhat disappointing, given the result observed in the reaction of aldehyde 12 with allyltrichlorostannane 5 (Scheme 3).

The relative stereochemistries for both 47and 49were determined by applying the same methodology described before for 13-16(Table 5). The 1,2-antiisomer is the major product as can be observed from the ¹³C NMR chemical shifts for the more shielded Me_c (Figure 8). In the case of 49and 50, the ¹³C chemical shifts for Me_c in 50appears more shielded (14.7 ppm) when compared to 49 (15.6 ppm).

Conclusions

The examples presented in this work show that the levels of π-facial selection are dependent on the absolute stereochemistries of the aldehydes as well as of the allyltrichlorostannanes. The results from these experiments suggest that the stereochemical relationships between the allyltrichlorostannane and aldehyde substituents may confer either a reinforcing (matched) or opposing (mismatched) facial bias on the carbonyl moiety. One possible reason for this result could be attributed to the involvement of energetically similar chair and twist-boat transition states that lead to diastereomeric product formation. Another possibility to consider in these reactions is that nonbonded interactions between the allyltrichlorostannane and α substituents on the aldehyde may not be significant in pericyclic transition states leading to either Felkin or anti-Felkin addition products.¹³ We believe that this chemistry is significant in the context of acyclic diastereoselection and will prove to be useful in the synthesis of more complex molecules, like polyacetate and polypropionate-derived natural products.^27,28

Acknowledgments

We are grateful to FAEP-UNICAMP, FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and INCT-INOFAR Proc. CNPq 573.564/2008-6 for financial support. We thank also Prof. Carol H. Collins for helpful suggestions about English grammar and style.

Supplementary Information

Available free of charge at http://jbcs.org.br, as PDF file.

Received: February 9, 2009

Web Release Date: April 30, 2009

FAPESP helped in meeting the publication costs of this article.

Supplementary Information

General Informations:All reactions were carried out under an atmosphere of argon or nitrogen in flame-dried glassware with magnetic stirring. Dichloromethane, triethylamine, 2,6-lutidine, diisopropylamine, dimethylformamide and N-methylpyrrolidone were distilled from CaH₂. Dimethyl sulfoxide was distilled under reduced pressure from calcium hydride and stored over molecular sieves. THF and toluene were distilled from sodium/benzophenone ketyl. Petrol refers to the fraction boiling between 40-60 ºC. Purification of reaction products was carried out by flash chromatography using silica-gel (230-400 mesh). Analytical thin layer chromatography was performed on silica gel 60 and GF (5-40 µm thickness) plates. Visualization was accomplished with UV light and anisaldehyde, ceric ammonium nitrate stain or phosphomolybdic acid followed by heating or I₂ staining. ¹H-NMR spectra were taken in CDCl₃ at 300 MHz or at 500 MHz spectrometer and are reported in ppm using solvent as an internal standard (CDCl₃ at 7.26 ppm) unless otherwise indicated. Data are reported as (ap = apparent, s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, sext = sextet, ap t = apparent triplet, m = multiplet, br = broad, td = triplet of doublets, quint d = quintet of doublets, coupling constant(s) in Hz; integration. Proton-decoupled ¹³C-NMR spectra were taken in CDCl₃ at 75 MHz spectrometer and are recorded in ppm using solvent as an internal standard (CDCl₃ at 77.0 ppm) unless otherwise indicated.

Allylsilanes 2-4 (General Procedure):In a 3-necked 500 mL round bottomed flask powdered CeCl₃.7H₂O (15.44 g, 41.4 mmol) was heated under vacuum (1 Torr) at 160 ºC for 12 h with vigorous stirring, resulting in the formation of a mobile white solid. The reaction flask was flushed with argon and allowed to cool to rt when anhydrous THF (65 mL) was added to the vigorously stirred anhydrous cerium(III) chloride forming a uniform white suspension, which was kept under stirring for 2 h. During this time, a separate three-necked 100 mL flask, fitted with a condenser and a pressure-equalizing dropping funnel, was charged with Mg turnings (1 g, 41.4 mmol), and the whole apparatus was flame dried under a flow of argon. To this flask was added dropwise a solution of ClCH₂SiMe₃ (5.8 mL, 41.4 mmol) in anhydrous THF (27 mL). This mixture was stirred for 3 h until almost all of the Mg had dissolved. The anhyd CeCl₃ suspension was now cooled to -78 ºC. To this suspension was added dropwise the previously prepared Grignard reagent, forming an off-white suspension, which was stirred at -78 ºC for 2 h. At this time, a solution of the corresponding ester (13.8 mmol) in anhydrous THF (8 mL) was added to the Grignard-cerium chloride complex dropwise over 5 min, and the resulting mixture was warmed gradually to r.t. When consumption of the starting ester was complete, as determined by TLC (3 h), the resulting grey solution was cooled to 0 ºC and quenched by the addition of a sat. aq solution of NH₄Cl (30 mL). The organic layer was separated, and the aqueous layer was extracted with Et₂O (2 x 50 mL). The combined organic layers were washed with brine (2 x 50 mL) and dried (MgSO₄). The solvent was removed under reduced pressure to give a slightly yellow liquid that was dissolved in CH₂Cl₂ (100 mL). To this flask was added Amberlyst 15 (1.0 g) and this mixture was stirred at rt until complete consumption of starting material. The resin was then removed by filtration and washed with CH₂Cl₂ (100 mL). The solvent was removed under reduced pressure to give allylsilanes 2-4.

Trimethyl(2-methylenepentadecyl)silane (2):yellow oil; Yield: 68%; TLC: R_f0.75 (EtOAc/hexane 20%); IR (Film): ν 3072, 2953, 2926, 2854, 1633, 1466, 1248, 1157 cm^-1; ¹H NMR (CDCl₃, 300 MHz): δ 0.04 (s, 9H), 0.91 (t, J= 7.0 Hz, 3H), 1.29 (brs, 20H), 1.39-1.49 (m, 2H), 1.57 (s, 2H), 1.97 (t, J= 7.0 Hz, 2H), 4.52 (brs, 1H), 4.60 (d, J= 1.0 Hz, 1H); ¹³C NMR (CDCl₃, 75 MHz): δ 2.1 (CH₃), 14.2 (CH₂), 22.5 (CH₂), 22.8 (CH₂), 27.8 (CH₂), 29.4 (CH₂), 29.6 (CH₂), 29.8 (CH₂), 32.0 (CH₂), 37.9 (CH₂), 109.4 (CH₂), 146.2 (C₀).

(R)-(4-(benzyloxy)-3-methyl-2-methylenebutyl) trimethylsilane (3):Yield: 88%; Rf= 0.38 (EtOAc/hexanes 5%); [α]_D²²: +12.6 (c1.3, CHCl₃); IR (film) ν (cm^-1): 3069, 3030, 2957, 2851, 1632, 1497, 1453, 1414, 1364, 1247, 1158, 1097, 1031, 952, 852, 735, 696, 634 cm^-1; ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 0.03 (s, 9H), 1.04 (d, J= 6.8 Hz, 3H), 1.46 (d, J= 13.6 Hz, lH), 1.52 (d, J= 13.6 Hz, lH), 2.28 (m, lH), 3.26 (dd, J =9.3, 8.3 Hz, 1H), 3.53 (dd, J =9.3, 5.4 Hz, lH), 4.52 (d, J= 12.1 Hz, lH), 4.53 (d, J= 12.1 Hz, lH), 4.62 (s, lH), 4.64 (s, lH), 7.25-7.40 (m, 5H); ¹³C NMR (CDCl₃, 75 MHz), δ (ppm): -1.3, 17.1, 26.6, 41.0, 72.9, 75.0, 106.5, 127.4, 127.5, 128.3, 138.7, 149.7; Elemental analysis: calcd. for C₁₆H₂₆OSi: C, 73.22%; H, 9.98%; found: C, 73.15%; H, 10.02%.

(S)-(3-(benzyloxy)-2-methylenebutyl)trimethylsilane (4):Rf= 0.34 (EtOAc/hexanes 5%); [α]_D²²: +12.6 (c1.3, CHCl₃); IR (film) ν (cm^-1): 3068, 3023, 2951, 1720, 1603, 1495, 1454, 1248, 1093; ¹H NMR (CDCl₃, 300 MHz), δ (ppm): 0.08 (s, 9H), 1.30 (d, J= 6.6 Hz, 3H), 1.48 (d, J= 14.5 Hz, 1H), 1.62 (d, J= 14.5 Hz, 1H), 3.84 (q, J= 6.6 Hz, 1H), 4.35 (d, J =11.7 Hz, 1H), 4.57 (d, J =11.7 Hz, 1H), 4.80 (s, 1H), 5.00 (s, 1H), 7.25-7.40 (m, 5H); ¹³C NMR (CDCl₃, 75 MHz), δ (ppm): -0.8, 20.6, 21.1, 70.0, 78.8, 108.7, 127.2, 127.5, 128.2, 138.8, 147.6.

Allyltrichlorostannane (5):¹H NMR (CDCl₃, 300 MHz) δ (ppm): 3.06 (d, J= 5,2 Hz, lH), 5.33 (d, J= 5.6 Hz, lH), 5.40 (d, J =6.6 Hz, 1H), 5.97 (m, lH); ¹³C NMR (CDCl₃, 75 MHz) δ (ppm): 35.0, 121.0, 127.0. Obs. The signal at 0.45 ppm corresponds to TMSCl.

Trichloro(2-methylenepentadecyl)stannane (6):¹H NMR (CDCl₃, 300 MHz): δ 0.89 (t, J = 6.0 Hz, 3H), 1.30 (brs, 20H), 1.51 (m, 2H), 2.14 (t, J = 8.0 Hz, 2H), 3.15 (s, 2H), 5.07 (brs, 1H), 5.10 (brs, 1H). Obs. The signal at 0.45 ppm corresponds to TMSCl.

(R)-(4-(benzyloxy)-3-methyl-2-methylenebutyl) trichlorostannane (7):¹H NMR (CDCl₃, 300 MHz) δ (ppm): 0.95 (d, J= 7.0 Hz, 3H), 2.48 (m, lH), 3.19 (d, J= 11.2 Hz, lH), 3.36 (d, J= 11.2 Hz, lH), 3.53 (dd, J =9.9, 8.4 Hz, 1H), 3.70 (dd, J =9.9, 4.4 Hz, lH), 4.71 (d, J= 13.2 Hz, lH), 4.77 (d, J= 13.2 Hz, lH), 5.04 (s, lH), 5.18 (s, lH), 7.30-7.50 (m, 5H). Obs. The signal at 0.45 ppm corresponds to TMSCl; ¹³C NMR (CDCl₃, 75 MHz) δ (ppm): 15.7, 39.9, 42.7, 73.0, 74.5, 114.6, 127.5, 128.3, 128.7, 138.7, 144.0. Obs. The signal at 3.6 ppm corresponds to TMSCl.

(S ) - ( 3 - ( benzyloxy ) - 2 - methylenebutyl ) trichlorostannane (8):¹H NMR (CDCl₃, 300 MHz, -60 ºC) δ (ppm): 1.28 (d, J= 6.6 Hz, 3H), 2.91 (d, J= 14.5 Hz, 1H), 3.05 (d, J= 14.5 Hz, 1H), 4.17 (q, J= 6.6 Hz, 1H), 4.68 (d, J =11.7 Hz, 1H), 5.01 (s, 1H), 5.05 (s, 1H), 5.10 (d, J =11.7 Hz, 1H), 7.20-7.40 (m, 5H). Obs. The signal at 0.45 ppm corresponds to TMSCl.

Homoallylic Alcohols (General Procedure):To a solution of the corresponding allylsilane (1.5 mmol) in CH₂Cl₂ (5 mL) at rt was added SnCl₄ (1.1 mmol). The resulting solution was stirred at rt for 2 h and then cooled to -78 ºC when a solution of aldehyde (1.2 mmol) in CH₂Cl₂ (2 mL) was added. This mixture was stirred for 2 h at -78 ºC and quenched by the slow addition of a sat. aq solution of NaHCO₃ (5 mL) followed by CH₂Cl₂ (5 mL). The layers were separated and the aqueous layer was extracted with CH₂Cl₂ (2 x 5 mL). The combined organic layers were dried (MgSO₄), filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel (30% EtOAc-hexane) gave the corresponding homoallylic alcohols.

(2S,3S)-2-(tert-butyldimethylsilyloxy)hex-5-en-3-ol (13) and (2S,3R)-2-(tert-butyldimethylsilyloxy)hex-5-en 2H), 5.07 (brs, 1H), 5.10 (brs, 1H). Obs. The signal at 0.45 3-ol (14):Yield: 45%; Rf= 0.26 (EtOAc/hexanes 5%); IR ppm corresponds to TMSCl. (film) ν (cm^-1): 3568, 3468, 2956, 2957, 2932, 2858, 1641, 1473, 1389, 1074, 1005, 968, 912, 777; ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 0.08 (s, 3H), 0.09 (s, 3H), 0.91 (s, 9H), 1.17 (d, J= 6.2 Hz, 3H), 2.18-2.32 (m, 2H), 3.33-3.43 (m, 1H), 3.70-3.82 (m, 1H), 5.01-5.16 (m, 2H), 5.81-5.59 (m, 1H). Minor isomer: 0.07 (s, 3H), 1.12 (d, J= 6.2 Hz, 3H), 3.53-3.60 (m, 1H), 3.76-3.82 (m, 1H); ¹³C NMR (CDCl₃, 75 MHz) δ (ppm): -4.7, -4.0, 18.2, 20.2, 25.9, 38.1, 70.9, 75.2, 116.8, 135.1; Minor isomer (14): 17.5, 36.8, 74.5, 117.2.

(2S,3S)-2-(tert-butyldimethylsilyloxy)-5-methyleneoctadecan-3-ol (15) and (2S,3R)-2-(tert - butyldimethylsilyloxy)-5-methyleneoctadecan-3-ol (16):Yield: 40%; Rf= 0.36 (EtOAc/hexane 5%); IR (film)ν (cm^-1): 3465, 3067, 2957, 2930, 2857, 1645, 1371, 1255, 1092, 835, 775; ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 0.08 ( s, 6H), 0.88 (m, 3H), 0.89 (s, 9H), 1.16 (d, J= 6.0 Hz, 3H), 1.25 (brs, 22H), 1.36-1.49 (m, 2H), 2.01-2.18 (m, 2H), 3.49 (dq, J= 4.4 Hz, 6.6 Hz, 1H), 3.66-3.75 (m,1H), 4.81 (d, J= 4.7 Hz, 2H); Minor isomer: 0.06 (s, 6H), 1.12 (d, J= 6.0 Hz, 3H), 3.56-3.66 (m,1H); ¹³C NMR (CDCl₃, 63 MHz) δ (ppm): -4.8, -4.1, 14.1, 18.0, 22.7, 25.8, 27.7, 29.4, 29.7, 31.9, 71.0, 73.4, 111.3. Minor isomer: 20.0, 29.7, 73.0.

(2S,3S)-2-(benzyloxy)hex-5-en-3-ol (17) and (2S,3R)2-(benzyloxy)hex-5-en-3-ol (18):Yield: 40%; Rf= 0.44 (EtOAc/hexane 10%); IR (film) ν (cm^-1): 3566, 3453, 3062, 3030, 2969, 2871, 1603, 1645, 1454, 1072, 1028, 993, 914, 737, 698; ¹H NMR (CDCl₃, 500 MHz) δ (ppm): 1.21 (d, J= 6.0 Hz, 3H), 2.15-2.26 (m, 1H), 2.31-2.40 (m, 1H), 3.44 (apqt, J= 6.2 Hz, 1H), 3.52 (ddd, J= 4.4 Hz, 6.2 Hz, 7.7 Hz, 1H), 4.38 (d, J= 11.7 Hz, 1H), 4.66 (d, J= 11.7 Hz, 1H), 5.09 (d, J= 9.5 Hz, 1H), 5.12(d, J= 20.3 Hz, 1H), 5.87 (ddt, J= 7.3 Hz, 9.5 Hz, 20.5 Hz), 7.26-7.38 (m, 5H). Minor isomer: 1.15 (d, J= 6.2 Hz, 3H); ¹³C NMR (CDCl₃, 63 MHz) δ (ppm): 15.4, 37.5, 71.0, 74.2, 117.2, 127.8, 128.4, 134.7, 138.3. Minor isomer: 13.8, 36.9, 70.7.

3-ol (19) and (2S,3S,6R)-7-(benzyloxy)-2-(tert - butyldimethylsilyloxy)-6-methyl-5-methyleneheptan3-ol (20): Yield: 55%; Rf= 0.28 (EtOAc/hexanes 10%); IR (film) ν (cm^-1): 3465, 3067, 2957, 2930, 2857, 1645, 1371, 1092, 835, 775; ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 0.08 (s, 6H), 0.9 (s, 9H), 1.07 (d, J= 7.0 Hz, 3H), 1.15 (d, J= 6.2 Hz, 3H), 2.07 (dd, J= 9.2, 14.3 Hz, 1H), 2.31 (dd, J= 4.0, 14.3 Hz, 1H), 2.50 (m, 1H), 3.39 (dd, J= 6.6, 9.2 Hz, 2H), 3.42 (dd, J= 7.0, 9.2 Hz, 2H), 3.63 (m, 1H), 3.72 (m, 1H), 4.93 (s, 1H), 4.95 (s, 1H), 7.26-7.32 (m, 5H); ¹³C NMR (CDCl₃, 75 MHz) δ (ppm): -4.6, -4.2, 17.5, 18.1, 18.7, 25.9, 38.7, 39.3, 71.4, 73.0, 73.5, 74.5, 111.6, 127.4, 128.2, 138.2, 149.0.

(2 S, 6 R)-7-(benzyloxy)-6-methyl-5-methyleneheptane-2,3-diols (23) and (24):Yield: 67%; Rf= 0.26 (EtOAc/hexanes 50%); ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 1.02 (d, J= 7.0 Hz, 3H), 1.17 (d, J= 6.2 Hz, 3H), 2.13-2.29 (m, 2H), 2.51-2.55 (m, 1H), 3.39-3.51 (m, 2H), 3.70-3.77 (m, 1H), 3.84-3.92 (m, 1H) 4.51 (s, 2H), 5.00 (s, 2H); 5.30 (s, 2H), 7.28-7.38 (m, 5H); ¹³C NMR (CDCl3, 75 MHz) δ (ppm): 17.5, 36.8, 39.0, 69.9, 72.0, 73.1, 74.3, 112.8, 127.8, 128.2, 137.8, 148,8.

(4R,5S)-4-((R)-4-(benzyloxy)-3-methyl-2-methylenebutyl)-2,2,5-trimethyl-1,3-dioxolane (25) and (4S,5S)-4-((R)-4-(benzyloxy)-3-methyl-2-methylenebutyl)-2,2,5-trimethyl-1,3-dioxolane (26):Rf= 0.72 (EtOAc/hexanes 20%); IR (film) ν (cm^-1): 3047, 2986, 2934, 2872, 1645, 1454, 1377, 1223, 1080; ¹H NMR(CDCl₃, 300 MHz) δ (ppm): 1.02 (d, J= 6.4 Hz, 3H), 1.12 (d, J= 6.7 Hz, 3H), 1.31 (s, 3H), 1.49 (s, 3H), 2.07 (dd, J= 4.9, 15.6 Hz, 1H), 2.34 (dd, J= 8.4, 15.6 Hz, 1H), 2.07 (st, J= 6.7 Hz, 1H), 3.25 (dd, J= 7.2, 8.9 Hz, 1H), 3.43 (dd, J= 5.8, 8.9 Hz, 1H), 4.09 (qt, J= 6.4 Hz, 1H), 4.21 (dt, J= 5.3, 8.5 Hz, 1H), 4.33 (s, 2H), 4,93 (d, J= 13.7 Hz, 2H), 7.28-7.38 (m, 5H); ¹³C NMR (benzene-d6, 75 MHz) δ (ppm): 16.1, 17.4, 26.0, 28.9, 35.9, 40.4, 73.1, 74.0, 75.1, 76.9, 107.4, 110.7, 126.5, 127.6, 128.5, 139.3, 149.3.

(2 R,3 R,6 R)-7-(benzyloxy)-2-( tertbutyldimethylsilyloxy)-6-methyl-5-methyleneheptan3-ol (21) and (2R,3S,6R)-7-(benzyloxy)-2-(tert - butyldimethylsilyloxy)-6-methyl-5-methyleneheptan3-ol (22):Rf= 0.53 (hexanes: EtOAc, 95:05); IR (film) ν (cm^-1): 3463, 3031, 2950, 2857, 1645, 1559, 1497, 1455, 1255, 1092, 895; ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 0.09 (s, 3H), 0.09 (s, 3H), 0.91 (s, 9H), 1.09 (d, J= 7.0 Hz, 3H), 1.16 (d, J= 6.2 Hz, 3H) 2.03-2.35 (m, 2H); 2.50 (qt, J= 7.0 Hz,1H), 3.32-3.39 (m, 1H), 3.45-3.64 (m, 2H), 3.72-3.80 (m, 1H), 4.52 (s, 2H), 4.91 (s, 1H), 4.94 (s, 1H), 7.33-7.34 (m, 5H).Minor isomer: 0.07 (s, 3H), 0.08 (s, 3H), 0.90 (s, 9H), 1.11 (d, J= 2.2 Hz, 3H); ¹³C NMR (CDCl₃, 75 MHz) δ (ppm): -4.8, -4.2, 17.4, 18.0, 18.3, 19.7, 25.8, 38.9, 39.4, 71.0, 73.0, 79.7, 74.6, 111.4, 127.5, 128.3, 138.4, 149.2. Minor isomer: 17.2, 38.5, 39.6, 71.4, 74.8, 79.7, 74.6, 111.8.

(2 R, 6 R)-7-(benzyloxy)-6-methyl-5-methyleneheptane-2,3-diol (27) and (28):Rf= 0.65 (EtOAc/hexanes 50%); ¹H NMR (CDCl₃, 500 MHz) 1.01 (d, J= 7.0 Hz, 3H), 1.18 (d, J= 6.0 Hz, 3H); 2.02-2.57 (m, 3H); 3.87-3.34 (m, 4H) 4.49 (d, J= 2.3 Hz, 1H), 4.97 (d, J= 2.3 Hz, 1H), 7.28-736 (m, 5H). Minor isomer: 1.08 (d, J= 7.0 Hz, 3H), 1.15 (d, J= 6.0 Hz, 3H); ¹³C NMR (CDCl₃, 125 MHz) δ (ppm): 17.8, 19.0, 38.5, 40.1, 70.7, 73.2, 74.8, 113.0, 127.8, 128.4, 138.0, 148.8. Minor isomer: 17.3, 37.3, 39.7, 69.9, 75.0, 112.7, 127.7, 128.4.

(4R, 5 R)-4-((R)-4-(benzyloxy)-3-methyl-2-methylenebutyl)-2,2,5-trimethyl-1,3-dioxolane (29) and (4S,5R)-4-((R)-4-(benzyloxy)-3-methyl-2-methylenebutyl)-2,2,5-trimethyl-1,3-dioxolane (30):Yield: 50%; Rf= 0.38 (EtOAc/hexanes 5%); IR (film) ν (cm^-1): 3055, 2986, 2936, 2874, 1645, 1454, 1379, 1090, 898, 842; ¹H NMR (C₆D₆, 500 MHz) δ (ppm): 1.10 (d, J= 6.1 Hz, 3H), 1.13 (d, J= 7.0 Hz, 3H), 1,40 (s, 6H), 2.13 (dd, J= 4.0, 15.0 Hz, 1H), 2.32 (dd, J= 7.6, 15.0 Hz, 1H), 2.55 (apsex, J= 6.4 Hz, 1H), 3.23 (dd, J= 7.3, 8.8 Hz, 1H), 3.42 (dd, J= 5.8, 8.8 Hz, 1H), 3.62 (dq, J= 5.8, 8.2 Hz, 1H), 3.68-3.72 (m,1H), 4.33 (s, 2H), 4.91 (s, 2H), 4.91 (s, 1H), 5.02 (s, 1H), 7.15-7.31 (m, 5H). Minor isomer: 1.11 (d, J= 6.0 Hz, 3H), 1.31 (s, 3H), 1.49 (s, 3H), 2.06 (dd, J = 4.6, 15.4 Hz, 1H), 4.20 (m,1H), 4.25 (m,1H), 7.08-7.11 (m, 5H); ¹³C NMR (C₆D₆, 125 MHz) δ (ppm): 17.2, 17.8, 27.5, 27.6, 39.0, 40.0, 73.1, 75.1, 77.3, 81.6, 111.5, 128.0, 128.5, 139.3, 149.0. Minor isomer: 16.0, 17.4, 26.0, 28.9, 35.7, 40.2, 74.0, 75.0, 76.4, 108.0, 110.8.

(2S, 3R, 6R)-2,7-bis(benzyloxy)-6-methyl-5-methyleneheptan-3-ol (31) and (2S,3S,6R)-2,7bis(benzyloxy)-6-methyl-5-methyleneheptan-3-ol (32):Yield: 70%; Rf= 0.36 (EtOAc/hexanes 20%); IR (film) ν (cm^-1): 3454, 3061, 3026, 2970, 2872, 1643, 1498, 1454, 1367, 1264, 1090; ¹H NMR (CDCl₃, 250 MHz) δ (ppm): 1.04 (d, J= 7.0 Hz, 3H), 1.22 (d,J= 6.3 Hz, 3H), 2.09-2.53 (m, 3H), 3.33- 3.54 (m, 3H), 3.80-3.88 (m, 1H), 4.50 (s, 2H), 4.52 (d, J= 12.0 Hz, 1H), 4.63 (d,J= 12.0 Hz, 1H), 4.93 (s, 1H), 4.97 (s, 1H), 7.29-7.35 (m, 10H). Minor isomer: 1.09 (d, J= 7.0 Hz, 3H), 1.17 (d,J= 6.0 Hz, 3H), 3.62-3.72 (m, 1H), 4.00-4.10 (m, 1H); ¹³C NMR (CDCl₃, 63 MHz) δ (ppm): 14.8, 17.5, 39.0, 70.9, 73.0, 74.5, 112.0, 127.5, 127.7, 128.3, 138.1, 149.0. Minor isomer: 15.5, 17.2, 71.0, 71.7, 74.9, 138.7.

(2R,3R,6R)-2,7-bis(benzyloxy)-6-methyl-5-methyleneheptan-3-ol (33) and (2R,3S,6R)-2,7-bis(benzyloxy)-6-methyl-5-methyleneheptan-3-ol (34): Yield: 60%; Rf = 0.18 (EtOAc/hexanes 10%); IR (film) ν (cm^-1): 3695, 3055, 2976, 2930, 1715, 1452, 1072, 897; ¹H NMR (CDCl₃, 250 MHz) δ (ppm): 1.06 (d, J= 7.0 Hz, 3H), 1.21 (d, J= 6.0 Hz, 3H), 2.08-2.71 (m, 3H), 3.31-3.55 (m, 3H), 3.65-3.76 (m, 1H), 4.48 (d, J= 9.2 Hz, 1H), 4.51 (s, 2H), 4.66 (d, J= 11.3 Hz, 1H), 4.92 (s, 1H), 4.94 (s, 1H), 7.10-7.37 (m, 10H). Minor isomer: 1.20 (d, J= 6.3 Hz, 3H), 3.79-3.87 (m, 1H), 4.00-4.10 (m, 1H); ¹³C NMR (CDCl₃, 63 MHz) δ (ppm): 15.5, 17.4, 38.8, 39.1, 39.5, 71.1, 72.6, 74.5, 111.8, 127.7, 128.3, 138.3, 148.9. Minor isomer: 14.5, 17.2, 38.7, 70.8, 72.0, 74.8, 112.0, 126.0.

(2 S, 3 R, 6 S)-6-(benzyloxy)-2-( tert - butyldimethylsilyloxy)-5-methyleneheptan-3-ol (35) and (2S,3S,6S)-6-(benzyloxy)-2-(tert-butyldimethylsilyloxy)-5-methyleneheptan-3-ol (36):Yield: 35%; Rf= 0.17 (EtOAc/hexanes 5%); IR (film) ν (cm^-1): 3564, 3445, 3052, 2955, 2931, 2858, 1651, 1454, 1372, 1092; ¹H NMR (CDCl₃, 500 MHz) δ (ppm): 0.08 (s, 3H); 0.09 (s, 3H); 0.90 (s, 9 H); 1.16 (d, J= 6.2 Hz, 3H); 1.31 (d, J= 6.6 Hz, 3H); 2.03-2.34 (m, 2H); 3.55 (dq, J= 3.3, 1.5 Hz, 1H); 3.71-3.81 (m, 1H); 3.95-4.03 (m, 1H); 4.36 (d, J= 11.7 Hz, 1H); 4.56 (d, J= 11.7 Hz, 1H); 5.07 (s, 1H); 5.12 (s, 1H); 7.27-7.33 (m, 5H). Minor isomer: 0.07 (s, 3H); 0.08 (s, 3H); 0.89 (s, 9 H); 1.13 (d, J= 5.9 Hz, 3H); 1.32 (d, J= 6.2 Hz, 3H); ); 4.36 (d, J= 11.7 Hz, 1H); 4.53 (d, J= 11.7 Hz, 1H); 5.10 (s, 1H); 5.14 (s, 1H). ¹³C NMR (C₆D₆, 75 MHz) δ (ppm): -4.7, -4.2, 18.2, 19.2, 20.5, 26.0, 34.7, 70.2, 71.6, 74.9, 78.9, 113.7, 114.1, 127.8, 128.5, 139.2, 148.0. Minor isomer: -4.6, -4.3, 18.5, 21.2, 72.1, 74.6, 79.1.

(2 R, 3 R, 6 S)-6-(benzyloxy)-2-( tert- butyldimethylsilyloxy)-5-methyleneheptan-3-ol (37) and (2R,3S,6S)-6-(benzyloxy)-2-(tert- butyldimethylsilyloxy)-5-methyleneheptan-3-ol (38):Yield: 47%; Rf= 0.25 (EtOAc/hexanes 10%); IR (film) ν (cm^-1): 3564, 3435, 3052, 2960, 2931, 2862, 1647, 1454, 1371, 1090; ¹H NMR (CDCl₃, 250 MHz) δ (ppm): 0.09 (s, 6H), 0.90 (s, 9 H), 1.16 (d, J= 6.3 Hz, 3H), 1.31 (d, J= 6.6 Hz, 3H), 2.03-2.49 (m, 2H), 3.57 (dq, J= 4.1, 1.3 Hz, 1H), 3.65-3.76 (m, 1H), 3.92-4.05 (m, 1H), 4.36 (d, J= 11.7 Hz, 1H), 4.52 (d, J= 11.7 Hz, 1H), 5.10 (d, J= 1.6 Hz, 1H), 5.14 (s, 1H), 7.26-7.35 (m, 5H). Minor isomer: 0.08 (s, 3H), 0.89 (s, 9H), 1.15 (d, J= 6.3 Hz, 3H), 1.32 (d, J= 6.6 Hz, 3H), 4.36 (d, J= 11.7 Hz, 1H), 4.53 (d, J= 11.7 Hz, 1H), 5.07 (d, J= 1.6 Hz, 1H); ¹³C (CDCl₃, 63 MHz) δ (ppm): -4.8, -4.2, 18.0, 20.0, 20.1, 25.8, 35.3, 70.0, 71.5, 74.3, 78.4, 113.2, 127.7, 128.4, 138.7, 147.2; Minor isomer: 18.6, 20.3, 34.3, 74.6, 114.1.

(2S,6S)-6-(benzyloxy)-5-methyleneheptane-2,3-diol (39) and (40): Yield: 67%; Rf= 0.36 (EtOAc/hexanes 50%); ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 1.18 ( d, J= 6.6 Hz, 3H), 1.32 (d, J= 6.6 Hz, 3H), 2.14-2.45 (m, 2H), 3.61 (dt, J= 3.7, 8.8 Hz, 1H), 3.70 (br, 2H), 3.79-3.87 (m, 1H), 4.00 (q, J= 6.6 Hz, 1H), 4.41 (d, J= 11.7, 1H), 4.56 (d, J= 11.7, 1H), 5.07 (s, 1H), 5.10 (s, 1H), 7.27-7.37 (m, 5H). Minor isomer: 1.19 (d, J= 6.0 Hz, 3H), 1.33 (d, J= 6.6 Hz, 3H); ¹³C NMR (CDCl₃, 75 MHz) δ (ppm): 17.4, 19.9, 33.6, 70.1, 74.6, 78.7, 115.9, 127.7, 128.5, 137.8, 146.8. Minor isomer: 19.2, 19.4, 35.6, 70.3, 78.5.

(4R,5S)-4-((S)-3-(benzyloxy)-2-methylenebutyl)-2,2,5-trimethyl-1,3-dioxolane (41) and (4S,5S)-4-((S)3-(benzyloxy)-2-methylenebutyl)-2,2,5-trimethyl-1,3-dioxolane (42):Yield: 50%; Rf= 0.55 (EtOAc/hexanes 20%); IR (film) ν (cm^-1): 3055, 2986, 2934, 2872, 1647, 1454, 1371, 1086; ¹H NMR (C₆D₆, 300 MHz) δ (ppm): 1.01 (d, J= 6.2 Hz, 3H), 1.28 (d, J= 6.6 Hz, 3H), 1.31 (s, 3H), 1.48 (s, 3H), 2.10-2.33 (m, 2H), 3.55-3.93 (m, 1H), 3.91 (q, J= 6.6 Hz, 1H), 4.06 (apquint, J= 6.2 Hz, 1H), 4.30 (d, J= 12.0 Hz, 1H), 4.53 (d, J= 12.0 Hz, 1H), 5.10 (s, 1H), 5.14 (s, 1H), 7.07-7.37 (m, 5H). Minor isomer: 1.08 (d, J= 5.9 Hz, 3H), 1.39 (s, 3H), 1.41 (s, 3H), 3.75 (ddd, J= 3.3, 8.4 Hz, 1H), 4.21-4.40 (m, 2H); ¹³C NMR (C₆D₆, 75 MHz) δ (ppm): 15.9, 20.6, 27.5, 27.6, 31.4, 70.1, 74.0, 76.9, 77.2, 81.1, 107.4, 112.9, 139.6, 147.1. Minor isomer: 17.6, 26.0, 28.9, 33.4, 78.9, 78.6, 108.0, 113.2.

(2R,6S)-6-(benzyloxy)-5-methyleneheptane-2,3-diol (43) and (44):Yield: 90%; Rf= 0.40 (EtOAc/hexanes 50%); IR (film) ν (cm^-1): 3416, 3069, 2976, 2930, 2867, 1722, 1647, 1454, 1371, 1275, 1070; ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 1.19 (d, J= 6.6 Hz, 3H), 1.34 (d, J= 6.6 Hz, 3H), 2.14-2.27 (m, 2H), 2.40 (d, J= 3.3 Hz, OH), 3.49-3.55 (m, 1H), 3.61 (apqt, J= 6.2 Hz, 1H), 4.01 (q, J= 6.6 Hz, 1H), 4.44 (d, J= 12.0 Hz, 1H), 4.52 (d, J= 12.0 Hz, 1H), 5.05 (s, 1H), 5.14 (s, 1H), 7.26-7.37 (m, 5H). Minor isomer: 1.18 (d, J= 6.6 Hz, 3H), 1.32 (d, J= 6.6 Hz, 3H), 2.44 (d, J= 3.3 Hz, OH), 3.80-3.88 (m, 1H), 5.11 (s, 1H); ¹³C NMR (CDCl₃, 75 MHz) δ (ppm): 19.3, 19.5, 35.7, 70.3, 74.3, 78.5, 115.4, 127.7, 128.4, 137.8, 145.9. Minor isomer: 17.5, 20.0, 74.6, 78.7.

(4R,5R)-4-((S)-3-(benzyloxy)-2-methylenebutyl)-2,2,5-trimethyl-1,3-dioxolane (45) and (4S,5R)-4-((S)3-(benzyloxy)-2-methylenebutyl)-2,2,5-trimethyl-1,3dioxolane (46):Yield: 90%; Rf= 0.27 (EtOAc/hexanes 5%); IR (film) ν (cm^-1): 3053, 2963,2936, 2874, 1724, 1649, 1454, 1379, 1265, 1089, 912, 842; ¹H NMR (CDCl₃, 300 MHz) δ (ppm): 1.26 (d, J= 6.0 Hz, 3H), 1.31 (d, J= 6.6 Hz, 3H), 1.39 (s, 6H), 2.13-2.38 (m, 2H), 3.68-3.79 (m, 1H), 3.95-4.09 (m, 1H), 4.31-4.41 (m, 1H), 4.33 (d, J= 12.0 Hz, 1H), 4.50 (d, J= 12.0 Hz, 1H), 5.15 (s, 2H), 7.23-7.36 (m, 5H); Minor isomer: 0.99 (d, J= 6.6 Hz, 3H), 1.17 (d, J= 6.2 Hz, 3H), 1.35 (s, 3H), 1.46 (s, 3H), 5.06 (s, 2H); ¹³C NMR (CDCl₃, 75 MHz) δ (ppm): 17.9, 20.5, 27.6, 33.5, 70.2, 78.7, 81.2, 108.1, 113.7, 127.8, 128.5, 138.8, 146.6. Minor isomer: 16.1, 19.5, 26.1, 28.9, 30.8, 72.0, 74.0, 76.2, 112.9, 115.1.

(2S,3R,6S)-2,6-bis(benzyloxy)-5-methyleneheptan-3-ol (47) and (2S,3S,6S)-2,6-bis(benzyloxy)-5-methyleneheptan-3-ol (48):Yield: 70%; Rf= 0.55 (EtOAc/hexanes 20%); IR (film) ν (cm^-1): 3695, 3055, 2986, 2930, 2685, 1715, 1603, 1452, 1265, 1072, 744; ¹H NMR (CDCl₃, 250 MHz) δ (ppm): 1.20 (d, J= 6.3 Hz, 3H), 1.32 (d, J= 6.6 Hz, 3H), 2.12-2.46 (m, 2H), 3.51 (ddd, J= 4.3, 6.3, 12.6 Hz, 1H), 3.87-4.13 (m, 2H), 4.37 (d, J= 12.0, 1H), 4.49 (d, J= 11.7 Hz, 1H), 4.51 (d, J= 11.7 Hz, 1H), 4.61 (d, J= 11.7 Hz, 1H), 5.08 (s, 1H), 5.14 (s, 1H), 7.26-7.37 (m, 10H). Minor isomer: 1.22 (d, J= 6.3 Hz, 1H); ¹³C NMR (CDCl₃, 63 MHz) δ (ppm): 14.1, 19.9, 34.1, 70.7, 72.0, 77.5, 78.5, 114.0, 127.6, 128.4, 138.6, 146.7.Minor isomer: 15.2, 20.3, 34.5, 70.0, 71.0, 73.3, 78.4, 79.4, 114.2, 127.5, 126.9, 138.5, 146.9.

(2R,3R,6S)-2,6-bis(benzyloxy)-5-methyleneheptan-3-ol (49) and (2R,3S,6S)-2,6-bis(benzyloxy)-5-methyleneheptan-3-ol (50): Yield: 88%; Rf= 0.55 (EtOAc/ hexanes 10%); ¹H NMR (CDCl₃, 250 MHz) δ (ppm): 1.22 (d, J= 6.3 Hz, 3H), 1.32 (d,J= 6.3 Hz, 3H), 2.11-2.42 (m, 1H), 3.42-3.54 (m,1H), 3.68-3.83 (m,1H), 3.93- 4.08 (m, 1 H), 4.34- 4.69 (m, 4H), 5.09 (d, J= 15 Hz, 1H), 5.14 (d, J= 5.4 Hz, 1H), 7.23-7.35 (m, 10H). Minor isomer: 1.23 (d, J = 6.3 Hz, 1H); ¹³C NMR (CDCl₃, 63 MHz) δ (ppm): 15.6, 20.2, 34.9, 70.0, 71.1, 73.4, 77.8, 78.4, 113.5, 127.7, 127.8, 128.3, 128.4, 138.6, 146.9. Minor isomer: 14.7, 34.7, 70.9, 73.0, 114.6, 127.4, 127.5, 138.3.

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• ¹⁶
  Although the diastereoselectivity of the reactions of these aldehydes with allyltrichlorostannanes depends on their enantiomeric purity, crude aldehydes were used in all of the studies described in the text.
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  The ratios were determined by ¹H and ¹³C-NMR spectroscopic analysis of the purified product mixture; The synand anti-products could not be separated and were characterized as mixtures; All of the percentage values represent data obtained from at least three individual trials.
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• ²⁶
  Having confirmed the relative (synor anti) relationship between allylstannane-derived stereogenic centers, the absolute stereochemistry of the newly formed hydroxyl substituent was determined by ascertaining its relationship to the stereocenter originating from the aldehydes, which are of known configuration.
• ²⁷
  All new compounds were isolated as chromatographically pure materials and exhibited acceptable ¹H-NMR, ¹³C-NMR, IR, MS, and HRMS spectral data.
• ²⁸
  General procedure for allyltrichlorostannane coupling reactions: To a solution of 2.5 mmol of the corresponding allylsilane in 7 mL of dry CH₂Cl₂ at -78 ºC was added 2.5 mmol of SnCl₄ The resulting solution was stirred at -78 ºC for 30 min when 2.7 mmol of aldehyde in 2 mL of CH₂Cl₂ was added. This mixture was stirred at -78 ºC for 1 h and quenched by the slow addition of 0.2 mL of Et₃N, followed by 10 mL of saturated NH₄Cl solution. The layers were separated and the aqueous layer was extracted with CH₂Cl₂ (2x5 mL). The combined organic layer was dried (MgSO₄), filtered, and concentrated in vacuo Purification by flash chromatography on silica gel (30% EtOAc/ hexanes) gave the corresponding homoallylic alcohols.

Publication Dates

• Publication in this collection
  10 June 2009
• Date of issue
  2009