Selective C-H acylation of indoles with α-oxocarboxylic acids at the C4 position by palladium catalysis

The first Pd-catalyzed direct C-H acylation of indoles at the C4 position with alpha-oxocarboxylic acids using a ketone directing group is described. This reaction exhibits high regioselectivity with the tolerance of a wide scope of functional groups to afford diverse acylated indoles in moderate-to-good yields. The control experiments evidence the generation of acyl radicals via K2S2O8 promoted decarboxylation of alpha-oxocarboxylic acids and the involvement of a Pd-II/Pd-IV catalytic cycle. Importantly, the synthetically useful selectivity observed might be applied to prepare indole derivatives with anti-tumor activity as tubulin inhibitors.