Free-Radical Approaches to Stemoamide and Analogues

Abstract

Two approaches allowing access to the tricyclic stemona backbone are presented. Both approaches rely on a free-radical cyclization reaction as the key step. In the formal synthesis of (+/-)-stemoamide, the construction of the A ring of the natural product was achieved via a 5-exo-trig radical cyclization with atom transfer. The two diastereoisomers issuing from this cyclization showed different reactivity while forming the seven-membered ring of the final product. In the second part of this study, a 7-exo-trig free radical cyclization was realized allowing access to the (+/-)-9,10-bis-epi-stemoamide. This reaction was highly stereoselective and allowed the control of three of the four contiguous stereocenters present in the molecule.