Bifunctional Iminophosphorane Catalyzed Amide Enolization for Enantioselective Cyclohexadienone Desymmetrization

The organocatalytic enolization of 2-arylacetamides, followed by an enantioselective intramolecular conjugate addition to tethered 2,5-cyclohexadienones, yielding 3D fused N-heterocycles, is described. The transformation represents the first strong activating group-free activation of carboxamides via alpha-C-H deprotonation in a metal-free, catalytic, and enantioselective reaction, and is achieved by employing a bifunctional iminophosphorane (BIMP) superbase. The enolization of 2-arylacetamides, followed by an enantioselective intramolecular conjugate addition to tethered 2,5-cyclohexadienones, yielding saturated fused N-heterocycles, is described. The transformation is achieved by employing a bifunctional iminophosphorane (BIMP) superbase catalyst and represents the first unactivated carboxamide deprotonation in a metal-free, catalytic, and enantioselective transformation.image