Synthesis of (+)-Harmicine

Abstract

A facile convergent access to the important indole alkaloid (+)-harmicine is described, starting from tryptamine and (<i>R</i>)-acetoxysuccinic anhydride via the corresponding acetoxysuccinimide in very good overall yield. Regioselective reduction of an unsymmetrical imide carbonyl group and acid-catalyzed stereoselective intramolecular cyclization were the key features involved. The directing group to induce asymmetry was finally detached via the corresponding iodide by using tributyltin hydride chemistry.