Construction of chiral nitrogen stereocenters via enantioselective C–H activation

Abstract

Enantioselective C–H activation has recently emerged as a versatile method for selectively constructing point, axial, and planar chirality. Out of the main strategies in asymmetric catalysis, desymmetrization, enantioselection, and classical kinetic resolutions have been demonstrated in C–H activation reactions. To the best of our knowledge, dynamic kinetic resolution (DKR) via enantioselective C(sp³)-H activation to set point chirality remains unrealized. While the rapid inversion of nitrogen stereocenters typically presents a challenge to their enantioselective synthesis, this phenomenon provides a unique opportunity to selectively access nitrogen stereocenters via a DKR given the appropriate system. Here, we report the DKR of nitrogen stereocenters via a Pd-catalyzed enantioselective C–H olefination yielding enantioenriched tribenzo[b,d,f]azepines and dibenzo[b,f]azepines, thus demonstrating the feasibility of constructing enantioenriched nitrogen stereocenters by harnessing nitrogen inversion. The chiral tribenzo[b,d,f]azepine products exhibit high circularly polarized luminescence (CPL) performance, representing a novel scaffold for exploration in this area.