Biaryl and stilbene synthesis via catalytic decarboxylative cross-coupling
Résumé
Due to their biological activities, the synthesis of biaryls has been strongly studied during the last century. Over the past three decades, transition metal-catalyzed cross-coupling procedures have been developed as a methodology of choice for their synthesis. In spite of a high catalytic activity and high turnover number, many of these traditional cross-coupling present several disadvantages, mainly in terms of atom economy as they generally reacted aryl halides with arylmetal derivatives. To answer partially to this dilemma, Goossen et al., and others reported the decarboxylative cross-couplings starting from benzoic acids (Fig. 1) [1]. In this context, we envisioned to develop a new sustainable and environmentally friendly method for the synthesis of biaryls in which two benzoic acids couple together releasing thus only CO2 as co-product. While we initiated our researches, few catalytic systems made of Pd and Ag salts (used in large excess) were reported [2-4]. We pursued our investigations with the aim of developing an efficient and economically viable catalytic system made of Pd and Cu. Several reaction parameters were evaluated (solvent, temperature, metal sources, bases
) on the cross-coupling of 2.6-dimethoxybenzoic acid with 2-nitrobenzoic acid (Fig. 2). Additionally, we investigated deeply the kinetic of the reaction with the goal of understanding the mechanism. These studies allowed us to propose an efficient and economically viable procedure for the synthesis of asymmetric biaryls from two benzoic acids. To the best, 77% yield to biaryl was achieved. Figure 2: Cross-coupling of 2.6-dimethoxybenzoic acid with 2-nitrobenzoic acid Additionally, we will report as an extension of this work the synthesis of 1,1- and 1,2-diarylethylenes from cinnamic acids and aryl halides for which we develop a new Pd-catalyzed procedure (Fig. 3). Figure 3: Synthesis of 1,1- and 1,2-diarylethylenes from cinnamic acids and aryl halides The results of these investigations, together with the scope and limitations, will be presented in this communication. [1] N. Rodriguez, L. J. Goossen, Chem Soc Rev 40 (2011) 5030-5048. [2] J. Cornella, H. Lahlali, I. Larrosa, Chem Comm 46 (2010) 8276-8278. [3] K. Xie, S. Wang, Z. Yang, J. Liu, A. Wang, X. Li, Z. Tan, C.-C. Guo, W. Deng, Eur. J. Org. Chem. 2011 (2011) 5787-5790. [4] P. Hu, Y. Shang, W. Su, Angew Chem Int Ed 51 (2012), 5945-5949