N -heterocyclic carbenes: From design to synthesis and their application as nucleophilic catalysts

Our group has pioneered novel internal redox process of aldehydes possessing an internal α-reducible functionality mediated by N-heterocyclic carbenes (NHCs). Two discrete discoveries have been crucial to the success of our program. The first has been the identification of reaction parameters intimately related to the fate of the putative reactive intermediates to exquisitely allow access to a single reaction outcome (e.g. NHC-enolate vs homoenolate). The second, and more crucial, has been the development of new N-mesityl substituted triazolium and imidazolium salts that serve as precursors to the N-heterocyclic carbene nucleophilic catalyst. Our achiral and chiral, bicyclic N-mesityl triazolium salts have shown unprecedented reactivity and selectivity in a variety of conceptually new transformations. As such we have been the first to disclose highly enantioselective intermolecular annulations providing access to stereochemically rich heterocycles. Moreover, the synthesis of a novel N-mesityl aminoindanol-derived imidazolium salt allowed for the first time the investigation into the inherent reactivity differences that exist between two classes of NHCs (triazolium vs. imidazolium). Current efforts toward catalyst development via a combinatorial approach promise the opportunity to discover new enantioselective NHC-catalyzed processes