Catalytic Enantioselective Synthesis of Highly Functionalized Pentafluorosulfanylated Pyrrolidines

Abstract

The first catalytic asymmetric synthesis of highly functionalized pentafluorosulfanylated pyrrolidines is described. The method, based on a 1,3-dipolar cycloaddition reaction of aryl and heteroaryl-substituted glycine Schiff bases with pentafluorosulfanyl acrylic esters, gave access to a broad range of pyrrolidines bearing aryl, naphtyl, and heteroaryl groups. By using Xing-Phos as a catalyst, the corresponding products were obtained in good yields, good to high regioselectivity, and excellent diastereo- and enantioselectivities (up to 98 % ee). This methodology allowed the preparation of enantioenriched SF₅ compounds for the first time using an enantioselective approach.

Keywords: azomethile ylides; cycloaddition; fluorine; pentafluorosulfanyl; pyrrolidines.