Synthetic and Quantum Mechanical Studies into the N-Heterocyclic Carbene Catalyzed (4+2) Cycloaddition

The N-heterocyclic carbene catalyzed (4 + 2) cycloaddition between alpha,/beta-unsaturated acid fluorides and TMS dienol ethers provides cyclohexene fused beta-lactone intermediates stable below -20 degrees C. These can be intercepted reductively or with organolithium reagents to produce diastereomerically pure cyclohexenes (>20:1 dr) with up to four contiguous stereocenters. The mechanism has been investigated using theoretical calculations and by examining secondary kinetic isotope effects. Together these studies implicate the formation of a diastereomerically pure beta-lactone intermediate by a stepwise (4 + 2) cycloaddition involving Michael addition, aldol cyclization, and lactonization.