Gold-Catalyzed Enantioselective 1,2-Diarylation of Alkenes: Mechanistic Insights through Steric Mapping of the Ad-ChetPhos Ligand

The development of the chiral (P,N) ligand-enabled gold-catalyzed enantioselective 1,2-diarylation of alkenes is described. This methodology utilizes iodoaryl alkenes and N-substituted indoles to deliver 3-(3-indolyl)chromans with up to 66% yield and 99% enantiomeric excess (ee). Unlike the 1,2-migratory insertion/cross-coupling sequence observed in other transition metal catalysis, the current approach leverages the interplay of the π-activation mode and cross-coupling reactivity of gold, offering the products with complementary regioselectivity. The detailed mechanism, including an enantio-induction model, has been proposed and corroborated with DFT studies, highlighting the critical role of the axially chiral C2-symmetric dihydroazepino-binaphthyl unit of the (P,N) ligand (Ad-ChetPhos) in achieving high enantioselectivity. The topographic steric maps, quantified by calculating percentage buried volume (%VBur) of the catalyst, key intermediates, and transition states (TS), shed light on the dynamic steric environment imposed by Ad-ChetPhos ligand at various stages of the catalytic cycle. The results showed gradual development of the overall steric bulk around the gold center, reaching as high as 70.3% in the South-Eastern (SE) quadrant of the preferred enantio-inducing transition state, likely due to the twisting of chiral dihydroazepino-binaphthyl unit of the ligand toward this region to accommodate the incoming nucleophile in the chiral pocket located in the North-Eastern (NE) region. These insights underscore the role of the ligand’s conformational flexibility in accommodating the nucleophiles of varying sizes and thereby exerting precise control over the reaction outcome.