Late-Stage Diversification of Chiral N-Heterocyclic-Carbene Precatalysts for Enantioselective Homoenolate Additions

A library of chiral triazolium salts has been prepared by late-state diversification of a triazolium amine salt. By utilizing a primary amine as a functional handle, a single triazolium salt can be transformed into a variety of chiral N-heterocyclic carbene precatalysts. This approach makes the preparation of chiral N-heterocyclic carbenes possible by a single-step modification of a triazolium salt, rather than the usual need for multistep organic synthesis and challenging heterocycle formation for each member of a catalyst library. We have screened these catalysts for control of diastereo- and enantioselectivity in a gamma-lactam-forming reaction between alpha,beta-unsaturated aldehydes and cyclic ketimines.