Ir-Catalyzed Atroposelective Desymmetrization of Heterobiaryls: Hydroarylation of Vinyl Ethers and Bicycloalkenes

A highly regio-, diastereo-, and enantioselective, scalable Ir-catalyzed hydroarylation of electron-rich acyclic and tensioned cyclic olefins with heterobiaryls is described. The reaction of acyclic vinyl ethers, dihydrofuran, and norbornenes with a variety of aryl isoquinoline, quinazoline, and picoline derivatives takes place with simultaneous installation of central and axial chirality, reaching complete branched/linear or exo/endo ratios and excellent diastereo- and enantiomeric excesses when in situ formed [Ir-I/Tol-SDP] or [Ir-I/Tol-BINAP] complexes are used as the catalysts. Deuterium labeling experiments and a comprehensive computational study suggest that, despite fast double bond migratory insertion into Ir-H, the reaction proceeds through a modified Chalk-Harrod mechanism, starting with selectivity-determining insertion into Ir-C-Aryl. The regioselectivity is controlled by the electron-donating alkoxy group, whereas diastereo- and enantioselectivity have a complex origin, which depend on the relative orientation of the alkoxy group and the establishment of adequate pi-pi interactions between the biaryl and the phosphine.