Scope and Mechanistic Studies of the Cationic Ir/Me-BIPAM-Catalyzed Asymmetric Intramolecular Direct Hydroarylation Reaction

Abstract

Results of mechanistic studies on asymmetric hydroarylation of α-keto amides via direct C–H bond addition to a carbonyl group catalyzed by a cationic Ir/Me-BIPAM complex are presented in this paper. A catalytic cycle involving C–H bond cleavage to give an Ar-[Ir]+ intermediate, insertion of a carbonyl group into the aryl-iridium bond, giving iridium alkoxide, and finally reductive elimination to reproduce active [Ir]+ species is proposed. The mechanistic insight for the iridium hydride species indicated that the C–H bond cleavage is caused in a reversible manner. Furthermore, the kinetic isotope effect was measured by product analysis of the reaction to compare H/D, and it was determined that kH/kD was 1.85. These experimental results suggest that the C–H bond cleavage step is not included in the turnover-limiting step. In addition, Hammett studies of substrates (ρ = −0.99) demonstrated that electron-donating groups at the para position to the reactive C–H bond accelerate the reaction rate. This linear relationship obtained in the Hammett plot indicates that the nucleophilicity of the aryl-iridium intermediate is an important factor in this reaction. All of the data indicate that carbonyl insertion into aryl-iridium is included in the turnover-limiting step of the catalytic cycle.