The Stereochemical Course of Intramolecular Michael Reactions

We present a general model for understanding the stereochemical course of intramolecular Michael reactions. We show that the addition of beta-ketoester enolates to alpha,beta-unsaturated esters and imides bearing adjacent stereocenters (X, Y = H, Me, OR) leads to high levels of asymmetric induction. Reinforcing and nonreinforcing stereochemical relationships are evaluated from the syn and anti reactant diastereomers. On the basis of synthetic, spectroscopic, and computational studies, we propose that the outcomes of these reactions can be rationalized by a dipole-minimized chair transition-state model.