Construction of Contiguous Tetrasubstituted Chiral Carbon Stereocenters via Direct Catalytic Asymmetric Aldol Reaction of α-Isothiocyanato Esters with Ketones

Abstract

Construction of contiguous tetrasubstituted chiral carbon stereocenters via direct catalytic asymmetric aldol reaction of alpha-substituted alpha-isothiocyanato esters with unactivated simple ketones is described. A Bu(2)Mg/Schiff base catalyst promoted the aldol addition/cyclization sequence at room temperature, giving protected alpha-amino-beta-hydroxy esters with contiguous tetrasubstituted chiral carbon stereocenters in 99 to 68% yield, 98:2 to 74:26 dr, and 98 to 82% ee.