Double Activation Catalysis for α′‐Alkylidene Cyclic Enones with Chiral Amines and Thiols

Cooperative catalysis has contributed greatly to the progress of asymmetric synthesis. However, double‐activation catalysis has been less explored, especially for covalently tethered species. Here, we present a double‐activation strategy for α′‐alkylidene cyclic enone substrates that uses a chiral primary amine and 2‐mercaptobenzoic acid to promote regio‐ and chemoselective addition to generate the complex interrupted iminium ion species. Significantly enhanced reactivity and enantioselectivity were observed for β‐regioselective Michael addition and Friedel–Crafts alkylation with malononitriles and indoles, respectively, which produced a spectrum of chiral cyclic adducts with an exo ‐alkylidene group. Moreover, a HRMS study detected a few key covalently tethered intermediates among the substrates and catalysts, which helped elucidate the catalytic mechanism.