Directed Palladation: Fine Tuning Permits the Catalytic 2-Alkenylation of Indols

Key words

C-H activation - directed palladation - indoles

Significance

The synthesis of 2-vinyl indoles by a Pd-catalyzed C-H activation process induced by coordination from a N-picolinyl is described. By testing several different N-substituents e.g. oxazolino methyl, dimethylcarbamoyl, and allylmethylcarbamoyl, the picolinyl group is shown to be optimal for the C-H activation of the indole 2-position. In the three examples given (R = CO₂Me, SO₂Ph and CN), the reactions proceed in almost quantitative yields. Although not indicated, the starting substrate may be easily prepared
(T. Guengoer, P. Malabre, J. Teulon Synth. Commun. 1994, 24, 2247).

Comment

2-Vinyl or 2-styryl indoles are usually obtained from 2-prefunctionalized derivatives or, recently, by Pd-catalyzed Heck or cross coupling reactions of corresponding halide or boronic acid intermediates. This procedure, if generalized and tested for functional group tolerance, will provide an oxidative Heck route to 2-substituted indoles. The 2-alkenyl substituted indoles are useful intermediate, for example, in [2+4] cycloaddition chemistry.