Practical enantioselective synthesis of beta-substituted-beta-amino esters.

[reaction: see text] A practical, large-scale synthesis of a beta-amino ester 1 was developed. A chiral imine derived from (S)-phenylglycinol and 3-trimethylsilylpropanal was coupled with the Reformatsky reagent 3 with high diastereoselectivity (de > 98%) to give (SS)-4a as the major isomer. The amino alcohol residue of the coupling product 4 was oxidatively cleaved with sodium periodate in the presence of methylamine.