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

摘要

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