Small Change, Big Impact: Reversal of Diastereoselection in Cuprate Conjugate Additions to α,β-Unsaturated Lactams and Identification of a Competing Mechanism

Abstract

A seemingly minor change to a reactant is shown to cause a change in reaction mechanisms. Conjugate addition of organocopper reagents to bicyclic α,β-unsaturated lactams derived from pyroglutaminol is determined by the nature of the aminal group. Aminals derived from aldehydes give anti addition; those from ketones give syn addition. Divergence in diastereoselection occurs because the substrates react by different mechanisms, ultimately due to a small but significant difference in pyramidalization of the aminal nitrogen.