Direct Formation of Synthetically Useful Silyl-Protected Aldol Adducts via the Asymmetric Reductive Aldol Reaction

Nathan O. Fuller; James P. Morken

doi:10.1055/s-2005-868510

LETTER

Direct Formation of Synthetically Useful Silyl-Protected Aldol Adducts via the Asymmetric Reductive Aldol Reaction

Nathan O. Fuller, James P. Morken*
Department of Chemistry, Venable and Kenan Laboratories, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA
Fax: +1(919)9622388; e-Mail: morken@unc.edu;

Abstract

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Abstract

Examination of different silane reducing agents in the reductive aldol reaction revealed that Me₂ i-PrSiH is highly selective for formation of the silylated aldol adduct versus the derived acylated adduct. This silicon group provides more robust protection for the product β-hydroxyl group than the diethylmethylsilyl group, which was employed previously.

Key words

asymmetric synthesis - asymmetric catalysis - hydrosilylations - protecting groups - aldol reactions

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References

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General Procedure.
An oven-dried 2-dram vial was charged with 0.006 mmol of [(cod)RhCl]₂ and 0.016 mmol of (R)-BINAP in 400 µL of dry 1,2-dichloroethane. The catalyst solution was stirred for 1 h and then 1.25 mmol of Et₂MeSiH was added. After stirring 30 min, an additional 100 µL of 1,2-dichloroethane was added, followed by 0.30 mmol of phenyl acrylate and 0.25 mmol of butyraldehyde. The vial was sealed and the mixture was allowed to stir for 24 h at r.t. After 24 h, the solvent was evaporated and the crude mixture was purified via flash column chromatography to provide the expected silyl ether.