Synthesis of Biaryls via Decarboxylative Pd-Catalyzed Cross-Coupling Reaction

Link: Org Lett ASAP

Jean-Michel Becht,* Cédric Catala, Claude Le Drian, and Alain Wagner*

Université de Haute-Alsace, Ecole Nationale Supérieure de Chimie de Mulhouse, Laboratoire de Chimie Organique et Bioorganique, UMR-CNRS 7015, 3 rue Alfred Werner, 68093 Mulhouse Cedex, France, and Novalyst Discovery, Bioparc, Boulevard Sébastien Brant BP 30170, 67405 Illkirch Cedex, France

An alternative way to synthesize biaryl compounds other than the standard Suzuki-Miyaura coupling which could be expensive with commercially available boronic acid or ester coupling partners. This was conducted using aryl iodide and carboxylic acid coupling partner. Presumably, the carboxylic acid undergoes decarboxylation under the reaction conditions.

First, the system was optimized to find the best conditions (as seen in the table bel0w). PdCl2 was found to be the most optimal catalyst while solvent and base additive were found to be DMSO and Ag2CO3, respectively. In addition, the best ligand was discovered to be AsPh3, which was superior to other phosphines or stibines.

In contrast to other decarboxylative methods described previously, the current method worked well with both electron-rich and electron-poor systems as shown in the table below. In addition, this method could also be applied to the synthesis of 2,2',6-substituted hindered biaryls (entries 10, 13, 17, and 18) in good yields.

Further more, cross-coupling between heterocycle, such as a benzofuran carboxylic acid derivative, with aryl iodide 2 and between carboxylic acid 1 and 1-iodo-naphthalene (Scheme 1) were also possible and gave products in good yields.