Pd-Catalyzed One-Pot Synthesis of Indole-3-carboxylic Acids via a Sequential Water-Mediated Nucleophilic Addition to Amides/Esters and Carbon–Heteroatom Cross-Coupling Reaction Strategy

Using 4-bromoindole-3-carboxylic
acid derivatives (amides or esters)
as substrates, this paper successfully developed a trace water-promoted,
palladium-catalyzed “one-pot” reaction strategy for
synthesizing 4-amino/alkoxyindole-3-carboxylic acid products. With
PdCl2 (5 mol %) as the precatalyst, Xantphos as the ligand,
and cesium pivalate as the additive, this synthetic method innovatively
integrates nucleophilic substitution of amides/esters with Pd-catalyzed
C–N or C–O cross-coupling into a single reaction system,
achieving efficient synergy of multistep transformations. This approach
facilitates a modular and rapid assembly of multisubstituted indole-3-carboxylic
acids, exhibiting broad functional group compatibility while maintaining
good reaction yields.