[(E)-γ-(Dimethylphenylsilyl)allyl]diisopinocampheylborane: A highly enantioselective reagent for the synthesis of anti-β-hydroxyallylsilanes

Article abstract of DOI:10.1016/S0040-4039(00)01526-4

anti-β-Hydroxyallylsilanes are prepared with 88-95% e.e. via the asymmetric allylboration reactions of aldehydes and [(E)-γ-(dimethylphenylsilyl)allyl]diisopinocampheylborane (7). (C) 2000 Published by Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01526-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9413–9417
[(E)-g-(Dimethylphenylsilyl)allyl]diisopinocampheylborane: a
highly enantioselective reagent for the synthesis of
anti-b-hydroxyallylsilanes†
William R. Roush,* Anatoly N. Pinchuk and Glenn C. Micalizio
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
Received 29 August 2000; accepted 11 September 2000
Abstract
anti-b-Hydroxyallylsilanes are prepared with 88–95% e.e. via the asymmetric allylboration reactions
of aldehydes and [(E)-g-(dimethylphenylsilyl)allyl]diisopinocampheylborane (7). © 2000 Published by
Elsevier Science Ltd.
In 1990 we introduced diisopropyl 2-[(E)-g-(dimethylphenylsilyl)]allyl-1,3,2-dioxaborolane-
4,5-dicarboxylate (1) as a reagent for the formal g-hydroxyallylation of aldehydes.1,2 This
process involved allylboration of aldehydes using 1 to give the anti-b-hydroxyallylsilanes 3
which were epoxidized with dimethyldioxirane. Subsequent treatment of the intermediate
epoxysilane with acetic acid effected Peterson elimination, thereby providing the targeted diols
4 in excellent yield. Other g-silylallylboronate reagents—with different substituents on silicon—
were developed in our laboratory to permit Fleming–Tamao oxidation to be performed at the
stage of 3, thereby facilitating the synthesis of anti-3,4-but-1-enediols.2–4 Of greater significance
is the realization that this allylboration sequence constitutes an exceptionally simple route to
chiral, non-racemic allylsilanes which are of interest as reagents for subsequent CꢀC bond
forming events.5,6 For example, we recently demonstrated that the anti-b-hydroxyallylsilanes,
after conversion to a silyl ether (e.g. 5), undergo highly diastereoselective Lewis acid promoted
[3+2]-additions to aldehydes.7 A representative example is the chelate controlled addition of 5 to
benzyloxyacetaldehyde, which provides tetrahydrofuran 6 with >20:1 diastereoselectivity.
Additional applications of anti-b-hydroxyallylsilanes as nucleophilic chiral allylmetal reagents
are under investigation in our laboratory.8
* Corresponding author. E-mail: roush@umich.edu
†
This paper is dedicated to Professor Harry H. Wasserman on the occasion of his 80th birthday.
0040-4039/00/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01526-4

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This exceptionally simple synthesis of chiral allylsilanes, illustrated by the conversion of 2 to
3, is a potentially important addition to the allylsilane literature since highly diastereo- and
enantioselective syntheses of chiral allylsilanes are not generally available, especially for the
parent allylsilanes lacking substituents on the vinyl group.5,9,10 However, while the reactions of
1 with chiral aldehydes proceed with excellent diastereoselectivity,2 especially when performed in
the stereochemically matched manifold,11 this reagent has proven to be only moderately
enantioselective in reactions with achiral aldehydes (75–87% e.e. with the most favorable classes
of substrates).7,12 Therefore, we elected to develop a new reagent, [(E)-g-(dimethylphenylsi-
lyl)allyl]diisopinocampheylborane (7), which incorporates the diisopinocampheylboranyl chiral
auxiliary developed by H. C. Brown and coworkers.13 Allylboranes incorporating this group
have consistently proven to be more enantioselective than those based on the tartrate ester
auxiliary in 1.14,15 Accordingly, we expected that the new reagent 7 would provide access to the
targeted anti-b-hydroxyallylsilanes from achiral aldehydes with excellent enantioselectivity.4,16
Reagent 7 was synthesized by metallation of allyldimethylphenylsilane17 with n-BuLi and
KOtBu (1 equiv. each) in THF at −45°C,2 followed by addition of B-methoxydiisopinocam-
pheylborane (Ipc2BOMe).18 The mixture was stirred at −78°C for 30 min, then BF3·OEt2 (1.3
equiv.) was added to sequester MeOLi/MeOK and generate a −78°C solution of reagent 7 to
which was added a slight excess of aldehyde (typically 1.2 equiv.). The reaction mixture was
stirred at −78°C for 4 h, then was worked up oxidatively to give the product b-hydroxyallylsi-
lanes 8 in 60–86% yields following purification by silica gel chromatography. In no cases did we
observe any of the diastereomeric syn-b-hydroxyallylsilanes. As shown in Table 1,19 each of the
anti-b-hydroxy allylsilanes was obtained with an enantiomeric purity of 88–95% e.e., as
1
determined by Mosher ester analysis20 or H NMR chiral shift studies. In one case (reaction
with hydrocinnamaldehyde), the product % e.e. was confirmed by chiral HPLC analysis.8
Stereochemical assignments for allylsilanes 8a, 8b, 8e and 8f were made by comparison with
spectroscopic data for samples previously generated in our laboratory.2,7 Absolute stereochemi-
cal assignments for 8e and 8h were made by using the Mosher method,21 thereby confirming that
the sense of asymmetric induction of the Ipc auxiliary is the same in reagent 7 as for other
allylboranes containing this directing group.13 All other stereochemical assignments were made
by analogy to the cases outlined here.

9415
The results summarized in Table 1 clearly indicate that reagent 7 is substantially more
enantioselective than 1 (comparative enantioselectivity data for reactions performed with the
tartrate ester modified g-silylallylboronate 1 are included in Table 1).2,7 In principle, even higher
levels of enantiomeric purity should be achievable by using the carene-derived auxiliaries
developed by Brown,22 if the enantioselectivity obtained using 7 is insufficient for a specific
synthetic problem. It should also be possible to incorporate other substituents at silicon,2–4 in
order to fine tune the reactivity of the allylsilane reagent for subsequent CꢀC or CꢀX bond
forming events.
Although we have concentrated here on the synthesis of b-hydroxyallylsilanes 8 from achiral
aldehydes, it is expected that reagent 7 will also be useful in reactions with chiral aldehydes. One
such example is summarized below, in which aldehyde 9 with a remote chiral quaternary center
Table 1
Enantioselective reactions of achiral aldehydes with 7

9416
was used as the substrate. This reaction, using ent-7 prepared from (−)-Ipc2BOMe, provided the
b-hydroxyallylsilane 10 with 90:10 diastereoselectivity. The seemingly low selectivity of this
reaction is a direct consequence of the fact that the enantiomeric purity of 9 was only 92% e.e.
The observed diastereoselectivity is consistent with reagent ent-7 functioning at a ]90% e.e.
level in this reaction, with the minor enantiomer of 9 being funneled selectively into the minor
product diastereomer, and with the enantiomeric purity of the major product (10) being
correspondingly enhanced.23
A representative experimental procedure follows. Potassium t-butoxide (177 mg, 1.58 mmol,
1 equiv.) was dissolved in dry THF (3 mL) and cooled to −78°C. Phenyldimethylallylsilane (0.35
mL, 1.74 mmol, 1.1 equiv.) was added via syringe in one portion followed by dropwise addition
of n-BuLi (0.73 mL of 2.16 M solution in hexanes, 1.58 mmol, 1 equiv.) over 5 min. The mixture
was stirred at −78°C for 10 min, then the flask was transferred into a −45°C bath (dry
ice–acetonitrile) and stirred for 2 h. The flask was returned to the −78°C bath and freshly
prepared18 (+)-Ipc2BOMe (500 mg, 1.58 mmol, 1 equiv.; generated from recrystallized Ipc2BH)
in THF (2 mL) was added slowly via cannula. The mixture was stirred at −78°C for 30 min, then
BF3·OEt2 (0.26 mL, 2.06 mmol, 1.33 equiv.) was added dropwise followed immediately by slow
addition of neat hexanal (0.23 mL, 1.9 mmol, 1.2 equiv.). After being stirred at −78°C for 4 h,
the reaction mixture was diluted with 1 M KH2PO4–KOH buffer (3 mL; pH 6) and 30% H2O2
(1 mL). The cooling bath was removed and the reaction mixture was stirred at ambient
temperature for 1 h, then cooled to 0°C and aqueous 1 M Na2SO3 solution (7 mL) was added
portionwise to destroy excess H2O2 (exothermic!). The resulting mixture was stirred for 15 min
at 0°C, then was extracted with ethyl acetate and washed with NaHCO3 solution, dried over
Na2SO4 and concentrated in vacuum. The residue was purified by chromatography over silica
gel using hexane–ether (95:5 to 90:10) mixtures as eluant to afford the product 8b as a colorless
oil, 377 mg (86% yield, based on Ipc2BOMe), [h]D=+2° (c 2.4, CHCl3), with an enantiomeric
purity of 95% e.e. based on Mosher ester analysis. In cases where separation of the allylation
product from residual aldehyde is difficult (as in the reaction using benzaldehyde as substrate),
the excess aldehyde was removed by treatment of the crude material with NaBH4 in THF–
MeOH at 0°C prior to chromatographic purification.
In summary, we have demonstrated that the chiral g-silylallylborane 7 undergoes highly
enantioselective reactions with a range of achiral aldehydes, thereby providing general access to
enantiomerically enriched b-hydroxyallylsilanes which are of interest for a range of CꢀC bond
forming processes. Additional studies using these compounds as reagents for organic synthesis
will be reported in due course.
Acknowledgements
This work was supported by grants from the National Institutes of Health (GM 38436 to
W.R.R. and CA 78333 to A.N.P.). We also thank Eli Lilly for an ACS Division of Organic
Chemistry Graduate Fellowship to G.C.M.

9417
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