Utilization of the Intramolecular Cycloaddition−Cationic π-Cyclization of an Isomünchnone Derivative for the Synthesis of (±)-Lycopodine

Abstract

A new annulation sequence leading to the tetracyclic skeleton of the Lycopodium family of alkaloids is effected by using the tandem cycloaddition-cationic pi-cyclization reaction of an isomünchnone dipole as the key strategic element. Synthesis of the required alpha-diazo imide precursor involved treating 5-methylcyclohex-2-en-1-one with the organocopper reagent derived from 3-methoxybenzyl chloride in the presence of chlorotrimethylsilane. Ozonolysis of the resulting silyl enol ether followed by a Wittig reaction and conversion to the desired alpha-diazo imide was carried out using standard malonylacylation and diazotization procedures. Treatment of the alpha-diazo imide with rhodium(II) perfluorobutyrate afforded a transient 1,3-dipole which subsequently cycloadded across the tethered pi-bond. The resulting cycloadduct was treated with BF(3).2AcOH to give a rearranged tetracyclic compound derived from a Pictet-Spengler-type cyclization of an N-acyliminium ion. The rearranged product was subsequently converted into a key intermediate previously used for the synthesis of (+/-)-lycopodine.