A Dual Role for the <i>N</i>-Perfluorobutanesulfinamide Auxiliary in an Asymmetric Decarboxylative Mannich Reaction

Herein, we demonstrate that the enhanced electrophilicity of <i>N</i>-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 β-amino thioesters in high yield. Additionally, we demonstrate that the <i>N</i>-perfluoroalkyl sulfinyl group can function as a phase tag for fluorous purification, thus enabling the rapid isolation of the chiral amine products by solid-phase extraction. The synthetic utility of this method is illustrated by the synthesis of sitagliptin, ruspolinone, and the natural product negamycin.