Cyclic ketimines as superior electrophiles for NHC-catalyzed homoenolate additions with broad scope and low catalyst loadings

Abstract

Cyclic sulfonyl imines derived from ketones were identified as stable and readily prepared compounds that serve as superior electrophiles for N-heterocyclic carbene (NHC)-catalyzed annulations with alpha,beta-unsaturated aldehydes to afford highly substituted gamma-lactams. Their superior reactivity and properties are highlighted by the first example of NHC-catalyzed reactions of enals with low catalyst loadings (0.5 mol %) and broad substrate scope encompassing alkyl, aryl, and heteroaromatic substituents. These findings and supporting studies suggest an alternative, ene-like mechanism rather than the catalytic generation of a catalyst-bound homoenolate equivalent.

Scheme 1

Possible reaction pathways for NHC-catalyzed annulations of enals and cyclic sulfonyl ketimines.

Scheme 2

Enantioselective annulation of cyclic ketimines.