Cooperative catalysis by carbenes and Lewis acids in a highly stereoselective route to gamma-lactams.

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. This type of 'cooperative catalysis', in which two or more catalytic cycles operate concurrently to achieve one overall transformation, has great potential in enhancing known reactivity and driving 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 gamma-lactams in moderate to good yields and with high levels of diastereo- and enantioselectivity.

Cooperative N-heterocyclic carbene/Lewis acid catalysis for highly stereoselective annulation reactions with homoenolates.

A new approach that takes advantage of N-heterocyclic carbene/Lewis acid cooperative catalysis provides access to cis-1,3,4-trisubstituted cyclopentenes from enals and chalcone derivatives with high levels of diastereoselectivity and enantioselectivity. The presence of Ti(OiPr)(4) as the Lewis acid allows for efficient substrate preorganization, which translates into high levels of diastereoselectivity. Additionally, we demonstrate the possibility of controlling the absolute stereochemistry of NHC-catalyzed reactions by employing a catalytic amount of a chiral Lewis acid as the unique source of optically active promoter.