Nickel-Catalyzed Atroposelective Synthesis of Axially Chiral Heterobiaryls via De Novo Benzene Formation

Axially chiral 1-aryl isoquinolines and their congeners have emerged as powerful ligands and organocatalysts in asymmetric catalysis. Herein, relying on enantio- and regioselective nickel-catalyzed reductive [2+4] annulation between heteroaryl-substituted alkynes and C(sp²)-type bis-electrophiles, we apply the general strategy of cross-electrophile de novo benzene formation in the highly atroposelective synthesis of diverse axially chiral heterobiaryls bearing isoquinoline, pyridine, pyrazine, or quinazoline substructure. Notably, high diastereoselectivities are also achieved in the case of the heterobiaryls containing two chiral axes. The synthetic utility of this method is exhibited by a variety of expedient downstream derivatizations.