Silyllithium-Initiated Coupling of α-Ketoamides with tert-Butanesulfinylimines for Stereoselective Synthesis of Enantioenriched α-(Silyloxy)-β-amino Amides

A silyllithium-initiated coupling of alpha-ketoamides with tert-butanesulfinylimines was developed for the efficient, stereoselective synthesis of enantioenriched alpha-(silyloxy)-beta-amino amides. Nucleophilic addition of silyllithium to alpha-ketoamides, followed by 1,2-Brook rearrangement, generates nucleophilic enolates, which are then intercepted by chiral imines to provide three-component coupling products. Use of alpha-ketoamides yields and diastereoselectivities in the resulting alpha-hydroxy-beta-amino acid derivatives.