Diastereoselective Multicomponent Cascade Reaction Leading to [3.2.0]-Heterobicyclic Compounds

Abstract

A general three-component triple cascade reaction through an iminium–enamine–iminium sequential activation initiated by a hetero-Michael addition to α,β-unsaturated aldehydes affords [3.2.0]­heterobicycles in high diastereoselectivity. The rate and diastereoselectivity of the reaction depended on the (<i>E</i>)-4-heterocrotonate and size of the secondary amine. The enantiomers of the major diastereoisomer of oxa- and azabicyclo[3.2.0]­heptane derivatives were separated by enzymatic kinetic resolution with immobilized <i>Candida antarctica</i> Lipase B (CALB), with <i>E</i> values up to 153. The absolute configuration of the nonacylated enantiomer of oxabicyclo[3.2.0]­heptane was determined by single crystal X-ray analysis