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

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.