Studies on the Alkylation of Chiral, Non-racemic, Tricyclic Pyrrolidinones

Abstract

Condensation of cyclic keto acids with chiral amino alcohols provides tricyclic pyrrolidinones with high levels of diastereoselectivity.These pyrrolidinones can be akylated via their lithium or sodium enolates.Optimal alkylation conditions vary with the nature of the amino alcohol; the phenylglycinol-derived pyrrolidinones suffer from an apparent benzylic metallation, whereas the valinol and norephedrine-derived substrates are good alkylation substrates.Application of this methodology to a vinylsilane / iminium ion cyclization approach to the synthesis of Whitesell's amine was also investigated.' The double alkylation product was isolated in 17% yield.