Lewis acid-promoted carbonyl addition of lithium (α-carbalkoxyvinyl)cuprates to aldehydes provides a novel asymmetric synthesis of β,β-disubstituted α-(hydroxyalkyl)acrylates

Abstract

A new anionic addition process has been developed for the asymmetric synthesis of unusual Baylis-Hillman adducts, β,β-disubstituted α-(hydroxyalkyl)acrylates. The new process involves conjugate addition of R 2CuLi to β-substituted α,β-acetylenic ester to give lithium (α-carbalkoxyvinyl)cuprate which was then subjected to the carbonyl addition to aldehyde promoted by Et 2AlCl. Modest to good diastereoselectivity (50.0 – 87.7 % de) has been obtained by using (1R,2S,5R)-(−)-menthol as the chiral auxiliary (59.0 – 94.0 % yield). The absolute configuration was unambiguously assigned by transforming the product to methyl (R)-α-methoxyphenylacetate.