An Asymmetric Domino Aza-Morita-Baylis-Hillman/Aza-Michael Reaction

Significance

The Sasai group reports an aza-Morita-Baylis-Hillman (MBH)/aza-Michael addition of α,β-unsaturated esters 2, tethered to an N-tosyl imine, and enones 1. The bifunctional Brønsted acidic Lewis base 3 turned out to be the catalyst of choice to obtain the desired isoindolines 4 in high yields and enantioselectivities. The authors suggest that the catalyst first reacts with 1 to form an enolate, which undergoes an aza-Michael reaction with 2. This aza-MBH intermediate subsequently collapses via an intramolecular aza-Michael addition, before the catalyst is released by elimination. Experiments supporting this proposal and demonstrating the utility of the products are also provided.