Synthesis of Highly Substituted Arenes via Cyclohexadiene-Alkene C-H Cross Coupling and Aromatization

The development of a cross-coupling method for the regioselective beta-alkenylation of 2,5-cyclohexadiene carboxylic acid derivatives to form ortho-alkenylarenes through in situ decarboxylation and aromatization is described. The carboxylic acid functionality is used as a traceless directing group for efficient and mild beta-alkenylation. The modular sequence comprises a reductive Birch alpha-alkylation, ionic delta-alkylation followed by a Pd-catalyzed decarboxylative beta-alkenylation with subsequent aromatization resulting in an overall three-fold ipso-para-ortho functionalization of readily accessed benzoic acid derivatives. Efficient synthesis of various alkyl-alkenylarenes under mild conditions in moderate to excellent yields is presented.