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

Abstract

The first Pd-catalyzed direct C–H acylation of indoles at the C4 position with α-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 α-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.