Covalent or Non-Covalent? A Mechanistic Insight into the Enantioselective Brønsted Acid Catalyzed Dearomatization of Indoles with Allenamides

The reaction mechanism of the enantioselective Brønsted acid catalyzed dearomatization of C(2),C(3)-disubstituted indoles with allenamides is investigated by means of density functional theory (DFT) calculations and ESI-MS analysis. The first step of the process (rate-determining step) is the formation of a covalent adduct between allenamide and the chiral organo-promoter. The resulting chiral a-amino allylic phosphate undergoes dearomative condensation with indoles. In the first step, the indole moiety remains bonded to the catalyst through strong hydrogen contacts. It can take on two different orientations that make the Re or Si prochiral face available to the subsequent electrophilic attack of allenamide. The attack on the indole faces originates two reaction paths leading to different stereoisomeric products, which differ in the configuration of the new stereocenter at the C3-indole position.