Asymmetric synthesis of α-mercapto-β-amino acid derivatives: application to the synthesis of polysubstituted thiomorpholines

Abstract

Tandem conjugate addition of homochiral lithium N-benzyl- N-(α-methyl- p-methoxybenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS t Bu proceeds with high diastereoselectivity to give a homochiral anti-α- tert-butylthio-β-amino ester. Stepwise deprotection gives the corresponding free α- tert-butylthio-β-amino acid without epimerisation. Tandem conjugate addition of homochiral lithium N-allyl- N-(α-methylbenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS t Bu followed by conversion of the S- tert-butyl group to a disulphide, and reduction with Lalancette’s reagent generates polysubstituted thiomorpholine derivatives.