Rh(III)‐Catalyzed Atroposelective Synthesis of Biaryls via C‐H Activation and Intermolecular Coupling with Sterically Hindered Alkynes

Chiral biaryls make important synthetic building blocks and privileged ligands for asymmetric catalysis. Reported herein is atroposelective synthesis of biaryl NH isoquinolones via Rh(III)-catalyzed C-H activation of benzamides and intermolecular [4+2] annulation with a broad scope of 2-substituted 1-alkynylnaphthalenes as well as sterically hindered symmetric diarylacetylenes. The axial chirality is constructed based on dynamic kinetic transformation of the alkyne in redox-neutral annulation with benzamides, with alkyne insertion being stereo-determining. The reaction also accommodates both benzamides and heteroaryl carboxamides and proceeds in excellent regioselectivity (if applicable) and enantioselectivities (average 91.6% ee). An enantiomerically and diastereomerically pure rhodacyclic complex has been prepared and offers insight into enantiomeric control of the coupling system, and the steric interactions between the amide directing group and the alkyne substrate serve to dictate both the regio- and enantioselectivity.