Catalysis-based enantioselective total synthesis of the macrocyclic spermidine alkaloid isooncinotine

Abstract

A concise and efficient total synthesis of the spermidine alkaloid (-)-isooncinotine (1) incorporating a 22-membered lactam ring is outlined. The approach is largely catalysis-based, involving a selective iron-catalyzed alkyl-aryl cross-coupling reaction of a difunctionalized pyridine substrate, a heterogeneous asymmetric hydrogenation step to set the chiral center of the target, and a highly integrated ring-closing metathesis/hydrogenation sequence to forge the saturated macrocyclic edifice in a single operation.