How achiral Brønsted acid is involved in co-catalyst model with chiral phosphoric acid for construction of quaternary carbon stereocenter

Summary

Chiral phosphoric acids, acting as bifunctional catalysts, play a dual role in activating both nucleophiles and electrophiles through non-covalent interactions. To enhance the activity of acid/base sites and create a favorable chiral steric environment, researchers have widely employed an efficient method, involving the introduction of an achiral Brønsted acid as reinforcement, in addition to structural modifications. However, the concrete catalytic model for this strategy remains relatively unexplored due to the increasing number of reaction sites on the catalysis heterodimer and the intricate spatial arrangement of multiple components in transition states. Here, we introduce a strategy of achiral Brønsted acid-assisted chiral-phosphoric-acid-catalyzed successive C–H functionalization/C–N cleavage and reassembly to construct an aza quaternary carbon stereocenter, in which the catalytic process and reaction mechanism were thoroughly investigated by in situ infrared studies and density functional theory calculations.