Semiempirical molecular orbital study on the transition states for the anti-selective Michael addition reactions of the lithium Z-enolates of N-alkylideneglycinates to α,β-unsaturated esters

Abstract

Semiempirical molecular orbital calculations (MNDO and PM3) show that the lithium Z-enolates derived from N-alkylideneglycinates react with α,β-unsaturated esters through a stepwise mechanism via the intermediate formation of Michael adducts. The initial step involves an anti-selective carbon–carbon bond formation through a Michael addition process and the second step consists of stereoselective ring formation or a 1,3-dipolar cycloaddition. The energy difference between the transition states for each step depends upon the steric hindrance caused by the alkylidene moiety: bulky alkylidene substituents prefer the formation of Michael adducts and small ones prefer 1,3-dipolar cycloadducts. The exclusively high anti-selectivity observed in the Michael addition step is due to the attractive molecular orbital interaction working between the imine moiety of donor molecules and the α-carbon of the acceptors.