A micellar catalysis strategy applied to the Pd-catalyzed C–H arylation of indoles in water

Abstract

The selective control over multiple competing C–H sites would enable straightforward access to functionalized indoles. In this context, we report here a modular and selective C–H arylation of indoles following the micellar catalysis approach using the third generation “designer” surfactant SPGS-550-M in the presence of 1 mol% of [(cinnamyl)PdCl]₂ under mild conditions. Thus, access to high value C-arylated (C-3 and C-2) indoles was achieved fulfilling the “triple bottom line philosophy” of green chemistry. The nature of the phosphine ligand was found to be critical for achieving site-selectivity, DPPF and DPPP being the most effective in promoting the arylation at C₃–H and C₂–H, respectively. The reaction is scalable and offers high chemo- (C vs. N) and regio-selectivity (C-3 vs. C-2) with a wide range of functional group tolerance. The surfactant aqueous solution can be recycled and reused without compromising on product yields.