Organocatalytic synthesis of chiral CF3-containing oxazolidines and 1,2-amino alcohols: asymmetric oxa-1,3-dipolar cycloaddition of trifluoroethylamine-derived azomethine ylides

Abstract

A catalytic asymmetric oxa-1,3-dipolar cycloaddition of ketones with trifluoroethylamine-derived azomethine ylides has been developed using cinchona-derived bifunctional thiourea catalysts. This protocol provides an efficient methodology for the facile synthesis of chiral CF₃-containing oxazolidines with moderate to excellent yields, excellent diastereoselectivities and enantioselectivities (58–98% yields, up to >20 : 1 dr and 98% ee). Remarkably, these oxazolidines could be facilely converted to CF₃-containing 1,2-amino alcohols with vicinal stereogenic centers, which is a privileged structural motif in medicinal chemistry.