The stereochemical course of intramolecular Michael reactions
Eugene E Kwan1, Jonathan R Scheerer, David A Evans
1Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
Abstract:
We present a general model for understanding the stereochemical course of intramolecular Michael reactions. We show that the addition of β-ketoester enolates to α,β-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.
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