Epoxides as Precursors to 1-Hydroxymethyl Indolizidine and Pyrrolizidine

Abstract

Herein we describe the synthesis of 1-hydroxymethyl pyrrolizidine and indolizidine alkaloids from epoxy-tethered pyrrole precursors. Two titanium-based methods are evaluated for the construction of the bicyclic scaffold: the Lewis acid mediated cyclization developed by Tanis and Raggon and the titanocene(III)-catalyzed reaction proceeding via radical intermediates. The former method, after hydrogenation of the pyrrole moiety, ultimately gives rise to enantiopure (–)-tashiromine, being the most concise and atom-economic procedure reported to date.