C O M M U N I C A T I O N S
Scheme 3. Effect of Water on Diastereoselectivity
the â,γ-unsaturated ester product (Table 2, entry 11). Good control
of olefin geometry (12:1) is seen, with the favored isomer consistent
with a trans elimination from the same diastereomeric intermediate
observed in γ-alkoxy substrates. Control of trisubstituted olefin
geometry in the formation of a sensitive â,γ-unsaturated ester
product is noteworthy.
In summary, the regioselective alkyne hydrosilylation by a trans
addition process, together with a one-pot C-C bond formation by
Si f C migration and subsequent silane oxidation, provides a new
strategy for the synthesis of â-carbonyl-substituted tertiary alcohols.
The importance of neighboring ketone and carboxylate groups in
promoting the oxidation of highly hindered tertiary silanes, an
observation that may affect synthetic design of routes depending
on such oxidations, was demonstrated.
Scheme 4. Determination of Product Diastereoselectivitya
Acknowledgment. We thank the National Science Founda-
tion and the National Institutes of Health, General Medical Science
(GM-13598), for their generous support of our programs. Z.T.B.
received support from an Althouse Family Stanford Graduate
Fellowship. Mass spectra were provided by the Mass Spectrometry
Regional Center of the University of California-San Francisco,
supported by the NIH Division of Research Resources.
a Conditions: (a) MeMgCl, THF, 67%. (b) Pd(OH)2/H2, then dimethoxy-
propane, PPTS, DMF, 52%.
and we reexamined the migration conditions. After excluding
several other factors, we found a remarkable dependence of
diastereoselectivity on the water content of the reaction medium
(see Scheme 3). Varying the water content altered the diastereomeric
ratio by 1 order of magnitude, from 1.5:1 (with 4 Å molecular
sieves; in this case the reaction yield was considerably lower) to
16:1 (with 50 equiv of water added, amounting to a 10:1 DMF/
water mixture). Adding water did increase reaction times somewhat
(1-2 h), but complete conversion and high isolated yields were
maintained. The extension of diastereoselective processes to ester
substrates was generally disappointing. In some cases very modest
selectivity could be obtained (Table 2, entry 8), while in others
protodesilylation competed with 1,2-migration, providing (E)-enone
and enoate byproducts. However, a change in acid derivatives to
acyl oxazolidinones remedied both of these problems, and excellent
yield and control of relative stereochemistry could be obtained
(Table 2, entries 9 and 10).14
Supporting Information Available: Characterization data for all
compounds, detailed experimental procedures, and details for the
synthesis of substrates (PDF). This material is available free of charge
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Vinylsilane substrates with γ-acyloxy substituents are also
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JA045971J
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