Enzymes are a continuing source of inspiration for the design of new chemical reactions
that proceed with efficiency, high selectivity and minimal waste. In many biochemical
processes, different catalytic species, such as Lewis acids and bases, are involved
in precisely orchestrated interactions to activate reactants simultaneously or sequentially.
Employing this type of cooperative catalysis, in which two or more catalytic cycles operate concurrently to achieve one overall
transformation, has great potential to enhance known reactivity and drive the development
of new chemical reactions with high value. In this disclosure, a cooperative N-heterocyclic carbene/Lewis acid catalytic system promotes the addition of homoenolate
equivalents to hydrazones generating highly substituted γ-lactams in moderate to good
yields and high levels of diastereo- and enantioselectivity.