Inverse stereoselectivity in the nucleophilic attack on five-membered ring oxocarbenium ions. Application to the total synthesis of 7-epi-(+)-goniofufurone

摘要

A highly stereoselective nucleophilic substitution at the anomeric position of 1,2-O-isopropylidene furanose derivatives was employed for the synthesis of 7-epi-(+)-goniofufurone and two of its stereoisomers. According to Woerpel's model, the stereoselectivity depends essentially on stereoelectronic factors that lead to a preferred nucleophilic attack on the inside face of the five-membered ring oxocarbenium ion in a folded conformation, whereby the stereochemical outcome generally is controlled by the substituent at the C3 position (OR group). Herein, we developed a strategy for a reverse stereoselective nucleophilic substitution, by placing an acetyl group at the C5 position of the xylofuranose ring, leading now to the nucleophilic approach on the outside face of the respective oxocarbenium ion. With this methodology, starting from diacetone-D-glucose derivative, we were able to achieve in seven steps the total synthesis of the powerful anti-tumour compound 7-epi-(+)-goniofufurone in a remarkable overall yield of 33%. (C) 2008 Elsevier Ltd. All rights reserved.