Organocatalytic atroposelective N-alkylation: divergent synthesis of axially chiral sulfonamides and biaryl amino phenols

Abstract

Axial chirality exists ubiquitously in numerous natural products and has been extensively recognized for decades in pharmaceuticals and enantioselective transformations. The development of efficient methodologies to obtain enantiopure structures bearing either a C–N or C–C axially chiral entity remains highly desired and sought after. Herein, a practical and universal organocatalytic atroposelective N-alkylation has been developed to efficiently access sulfonamides containing an allene or allyl entity. Furthermore, this process has also enabled selective N–H activation in the subsequent transformation towards functionalized sulfonamides, and realized the kinetic resolution of NOBIN analogues to afford chiral catalyst precursors. The racemization experiments show that substituted allenoate-sulfonamides possess higher rotational barriers than the corresponding acrylate-sulfonamides. This divergent synthetic procedure can be facilely scaled up and bodes well for its wide applications in enantioselective synthesis.