Mechanism and Origins of Regio- and Enantioselectivities of Iridium-Catalyzed Hydroarylation of Alkenyl Ethers.

The iridium-catalyzed hydroarylation of alkenyl ethers developed by Nishimura and co-workers (Ebe, Y.; Onoda, M.; Nishimura, T.; Yorimitsu, H. Angew. Chem. Int. Ed. 2017, 56, 5607-5611) represents a rare example of regio- and enantioselective hydroarylation of challenging internal alkenes. In the present study, density functional theory calculations were performed in order to investigate the detailed reaction mechanism and the origins of the experimentally observed regio- and enantioselectivities. The computations show that the initial C-H oxidative addition and the isomerization between the allylic ethers and the 1-alkenyl ethers via the migratory insertion into the Ir-H bond/β-hydride elimination are both feasible. The reaction was found to proceed through the modified Chalk-Harrod-type mechanism via the migratory insertion into the Ir-C bond/C-H reductive elimination. The migratory insertion into the Ir-C bond constitutes the rate- and selectivity-determining step of the overall reaction. The calculations reproduced quite well the experimentally observed regio- and enantioselectivities. The enantioselectivity of the reaction was found to arise from the reactions of the (E)- and (Z)-1-alkenyl ethers, which afford the opposite enantiomers of product with the aryl group installed at the α-position to the alkoxy group. It turns out that the strong electron-donating character of the alkoxy group plays an important role in determining the regioselectivity, since it can stabilize the developed positive charge of the α-insertion transition state, leading to the aryl group being selectively installed at the α-position.