Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

Abstract

A novel Rh-catalyzed one-pot homo-coupling reaction of aryl Grignard reagents was achieved. The reaction with bromobenzenes having an electron-donating group or a halogen substituent gave the corresponding homo-coupling products in good yields, although the reaction using heterocyclic or aliphatic bromides scarcely proceeded. A Rh(III)–bis(aryl) complex, which might be formed from RhCl(PPh3)3 and the aryl Grignard reagents, plays an important role in giving the homo-coupling products in this reaction. Furthermore, we applied the reaction to the synthesis of a novel inhibitor for integrins which is critical for several diseases.

Keywords

• biphenyltetracarboxylic acid
• homo-coupling
• integrin inhibitor
• rhodium catalyst
• ullmann-type reaction