Access to Polycyclic Alkaloid-Like Structures by Coupling the Passerini and Ugi Reactions with Two Sequential Metal-Catalyzed Cyclizations

Complex polycyclic compounds resembling some natural alkaloids have been prepared in only three high yielding steps by combining the Ugi or Passerini multicomponent reactions with two metal-catalyzed cyclizations: an intramolecular Tsuji-Trost reaction of the isocyanide-derived amide followed by a ring-closing metathesis. Scaffold diversity may be explored by the appropriate choice of starting unsaturated isocyanides. The Tsuji-Trost cyclization proceeds with moderate to good diastereoselectivity, and the major diastereomer was in most cases isolated in the pure form.