Mechanistic Insight into Rh-Catalyzed C(sp2)–O Bond Cleavage Applied to Cross-Coupling Reaction of Benzofurans with Aryl Grignard Reagents

A mechanistic study of the Rh-catalyzed cross-coupling reaction of vinylic ethers with aryl Grignard reagents via C(sp2)–O bond cleavage is reported herein. To obtain mechanistic insights, the reaction was conducted in a flow reactor, and kinetic studies revealed that the reaction obeyed first-order and zeroth-order kinetics, with respect to vinyl ether and aryl Grignard reagents, respectively. The olefinic ligands in the Rh precatalysts significantly affected the catalytic performance, and the catalytic activity of [RhCl(CH2═CH2)2]2 was ca. 110 times higher than that of [RhCl(cod)]2. Furthermore, the kinetic studies revealed that bidentate ancillary ligand, COD, forms a dormant species to decelerate the catalytic turnover. Computational studies suggested that the reaction between diarylrhodate, generated by the reaction of a Rh precatalyst with two molecules of aryl Grignard reagents, and vinylic ethers proceeded through Mg cation-assisted insertion/anti-β-oxygen elimination rather than oxidative addition/reductive elimination and nucleophilic substitution at the vinylic carbon (SN2 V). In the transition state, the Mg countercation was coordinated to the ethereal oxygen atom in the substrate and facilitated not only C–O bond cleavage but also the insertion of the C═C bond into the Rh–Ph bond. These strategies and mechanistic insights were successfully applied to develop a strategy for the Rh-catalyzed cross-coupling reaction of fused vinylic ethers, benzofurans, and aryl Grignard reagents, wherein the bond cleavage occurred selectively at the vinylic C(sp2)–O bond, even in the presence of Ar–O, Ar–Cl, or Ar–Br bonds. These results demonstrated the unique chemoselectivity of the present Rh-catalyzed reaction, which will allow the development of a complementary synthetic approach to the existing Ni-catalyzed cross-coupling reaction via C–O bond cleavage.