Stereoselective Formation of Quaternary Stereogenic Centers via Alkylation of α-Substituted Malonate-Imidazolidinones

Abstract

A new stereoselective alkylation methodology is presented for formation of chiral, nonracemic quaternary centers via a chiral auxiliary protocol involving α-alkylated malonate imidazolidinones. Based on two X-ray structures of quaternized products, the diastereoselectivity observed may be rationalized via a transition-state involving an s-transC-N conformation of the C-N bond of the auxiliary, with the metal cation (K(+)) chelated into the malonate six-membered hole as a Z-enolate. A deprotection protocol involving ethanethiolate exchange of the imide to the corresponding thioester, followed by a standard Fukuyama reduction and a borohydride reduction, furnishes α,α'-quaternized β-hydroxypropionates in high ee overall.