Intramolecular [4+1] pyrroline annulation as a general method for the synthesis of pyrrolizidine alkaloids

A general methodology for the synthesis of pyrrolizidine alkaloids has been developed. The two key steps in the sequence were the synthesis of the dienic azide system 1 and its regioisomer 2 by utilizing the vinylogous Reformatsky reaction, and the intramolecular additions of the azide moiety across the activated dienes with subsequent pyrolyses to provide the pyrrolizidines of type 3. This study broadened the scope of the vinylogous Reformatsky reaction to include the preparation of alkaloid synthons and introduced the heteroatom equivalent of the carbenoid [4+1] annulation as a method or alkaloid synthesis. [See docment for associated image]