Palladium-catalyzed esterification reaction of arenes/heterocyclic carboxylic acids with difluoroallyl bromide for the efficient preparation of difluoroallyl esters

Abstract

We report a palladium-catalyzed esterification reaction involving difluoroallyl bromides. This synthetic strategy involves the activation of fluorinated bromohydrocarbons by palladium catalysis and a direct C–O coupling reaction with a weakly nucleophilic indole carboxylic acid to obtain indole carboxylic esters. The key of this reaction lies in the selective coordination and activation of 3-bromo-3,3-difluoropropene by the palladium catalyst. The reaction overcomes the influence of the unique electronic effects of the difluoromethylene group on alkene reactivity, directly establishing an efficient new method for the synthesis of difluoroallyl esters, while exhibiting good substrate compatibility and moderate functional group tolerance. It not only applies to indole-based substrates but also can convert pyrrole/aromatic acids into the corresponding carboxylic esters. Overall, this study provides a practic al and straightforward synthetic approach for difluoroallyl-substituted indole/pyrrole/aromatic carboxylic esters.