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. (Figure presented)