Synthesis of vinylogous amides by gold(I)-catalyzed cyclization of N-Boc-protected 6-alkynyl-3,4-dihydro-2H-pyridines

J Org Chem. 2013 Nov 1;78(21):11007-16. doi: 10.1021/jo4019914. Epub 2013 Oct 14.

Abstract

The gold(I)-catalyzed cyclization of N-Boc-protected 6-alkynyl-3,4-dihydro-2H-pyridines, prepared by the Sonogashira coupling of lactam-derived enol triflates or phosphates, provides vinylogous amides, which are useful intermediates in the synthesis of natural compounds. The Au(I)-catalyzed reaction is carried out with Ph3PAuOTf as a catalyst and proceeds via a 6-endo-dig cyclization to form a vinylgold species that after protodeauration generates a cyclic carbamate intermediate. This intermediate is in most cases not isolated, but the addition of a base to the reaction mixture rapidly and quantitatively delivers the target vinylogous amide. The first synthesis of a natural compound from Sonneratia hainanensis has been accomplished by this approach.