A dual role for the N-perfluorobutanesulfinamide auxiliary in an asymmetric decarboxylative Mannich reaction

Fluorine substitution is a powerful strategy in asymmetric synthesis to tune the properties of chiral catalysts, ligands, and auxiliaries. Herein, we demonstrate that the enhanced electrophilicity of N-perfluorobutanesulfinamide auxiliary-derived imines enables a highly selective decarboxylative Mannich reaction under mild conditions. The molecular sieves-mediated transformation tolerates a broad substrate scope and produces chiral beta-amino thioesters in high yield and stereoselectivity. Additionally, we demonstrate that the N-perfluoroalkyl sulfinyl group can function as a phase tag for fluorous purification, thus enabling the rapid and simple isolation of the chiral amine products by solid-phase extraction. The synthetic utility of this method is illustrated by the synthesis of the bioactive natural product negamycin, and the small molecules sitagliptin and ruspolinone.