Pd-Catalyzed Synthesis of (Aza)Indoles from o-Haloanilines and Aldehydes

Significance

The synthesis of 2-unsubstituted indoles 3 from electron-poor ortho-haloanilines 1 and aldehydes 2 is described. The reaction is tolerant of a range of functional groups and substitution patterns. However, low yields are obtained when ortho-substituted anilines are used. Both chloro- and bromoanilines may be used with equal efficacy. Attempted reaction of electron-rich or electron-neutral o-haloanilines proved moderately effective, but inferior to those previously reported by the authors using a Pd(II)/XPhos system (Y. Jia, J. Zhu J. Org. Chem. 2006, 71, 7826). The reaction was also extended to the synthesis of a variety of azaindoles 5 from o-chloroaminopyridines 4, although higher temperatures are required for efficient conversion. In all cases, the major side product is the hydrodehalogenated aniline resulting from a reductive process.