Harnessing Arynes for Catalytic Enantioselective Construction of Axially Chiral Biaryls.

Axially chiral biaryls are privileged motifs in catalysis, bioactive molecules, and materials, and arynes should in principle provide concise access to these valuable scaffolds. However, the high reactivity, fleeting lifetime, and neutral character of arynes make selective catalytic control, particularly enantiocontrol, exceptionally challenging. As a result, existing aryne-based approaches to axial chirality have relied on stoichiometric chiral information rather than catalytic asymmetric induction. Herein, we disclose the first catalytic enantioselective construction of axial chiral biaryls from arynes through a palladium-catalyzed atroposelective [2 + 2 + 2] cycloaddition with internal and terminal arylalkynes. Enabled by a newly developed chiral P,N-ligand, (R)-JiaPhos, this transformation achieves efficient and stereocontrolled aryne capture even with only a slight excess of aryne precursor, affording structurally diverse axially chiral biaryls in high yields with excellent chemo- and enantioselectivities. Notably, this reaction exhibits a remarkably broad scope, accommodating tri- and tetra-ortho-substituted biaryls and both carboaryl and heteroaryl partners, and enabling access to C-C, C-N, and C-B axial chirality. Moreover, representative phosphine oxide products were readily transformed into a MOP ligand and a chiral DavePhos analogue by reduction, further underscoring the practical utility of this method.