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International @ BIOVERT+NRA:CPI:LDJ; International audience; 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

International @ BIOVERT+NRA:CPI:LDJ; International audience; 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 becoming methodologies 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 react aryl halides with arylmetal derivatives. To answer partially to this dilemma, Goossen et al., and others reported the decarboxylative cross-couplings in which arylmetal reagents are replaced by benzoic acids. Nowadays, the challenge is to develop new sustainable and environmentally friendly methods. In this context, inspired by the work of Goossen, we envisioned to develop a new method for the synthesis of biaryls in which two benzoic acids couple together releasing thus only carb on dioxide as by product. Another advantage is the accessibility, non-sensitivity and the rather low cost of benzoic acids that are potentially available from biomass. While we initiated our researches, few catalytic systems made of palladium and silver salts (used in large excess) were reported. However, we pursued our investigations with the aim of developing an efficient and economically viable catalytic system made of palladium and copper. Several reaction parameters were evaluated (i.e.: solvent, temperature, nature and loading of metal sources, bases, ligand…) on the cross-coupling of 2.6-dimethoxybenzoic acid with 2-nitrobenzoic acid. 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. The results of these investigations, together with the scope and limitations, will be presented in this communication. 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/Cu-catalyzed procedure.