ABSTRACT
Abstract The palladium-catalyzed annulation of alkynes by functionally-substituted aryl and vinylic halides or triflates provides a very convenient and efficient approach to a wide variety of heterocycles and carbocycles. This chemistry has lead to the discovery of a number of novel palladium-catalyzed processes in which the palladium migrates from one carbon to another within the molecule providing a unique way to form carbon-carbon bonds in remote locations within the same molecule. Introduction Some years ago we began a program to explore the scope of the palladiumcatalyzed annulation of alkenes, dienes and alkynes by functionally-substituted aryl and vinylic halides or triflates as a convenient approach to a wide variety of heterocycles and carbocycles. We subsequently reported annulations involving 1,2-, 1,3-and 1,4-dienes; unsaturated cyclopropanes and cyclobutanes; cyclic and bicyclic alkenes; and alkynes, much of which was reviewed in 1999 (Scheme 1).1 In recent days our work has concentrated on the annulation of alkynes. Recent developments in this area will be reviewed and some novel palladium migration processes that have been discovered during the course of this work will be discussed. Palladium-Catalyzed Annulation of Alkynes A wide variety of heterocycles can be readily prepared by the heteroannulation of alkynes. For example, the palladium-catalyzed annulation of internal alkynes by 2-iodoanilines provides easy access to 2,3-disubstituted indoles by a process that involves initial reduction of Pd(OAc)2 to Pd(0), oxidative addition of the aryl halide to Pd(0), cis-addition of the arylpalladium
species to the alkyne, and nucleophilic displacement of the Pd moiety by the nitrogen, which in turn regenerates the Pd(0) catalyst (Scheme 2).2 This chemistry works on a wide variety of alkynes and the regiochemistry of alkyne insertion is generally quite high with the more hindered group on the alkyne ending up next to the nitrogen. This chemistry has afforded a wide range of indoles and has been carried out on solid supports to afford indole libraries.
