Asymmetric Synthesis of Hydroquinolines with α,α-Disubstitution through Organocatalyzed Kinetic Resolution

The first kinetic resolution of hydroquinoline derivatives with alpha,alpha-disubstitution has been achieved through asymmetric remote aminations with azodicarboxylates enabled by chiral phosphoric acid catalysis. Mechanistic studies suggest a monomeric catalyst pathway proceeding through rate- and enantio-determining electrophilic attack promoted by a network of attractive non-covalent interactions between the substrate and catalyst. Facile subsequent removal and transformations of the newly introduced hydrazine moiety enable these protocols to serve as powerful tools for asymmetric synthesis of N-heterocycles with alpha,alpha-disubstitution.