Pd-Catalyzed Direct Arylation of Thienyl Derivatives with (Hetero)aromatic Bromides in Deep Eutectic Solvents

Within the framework of green chemistry, solvents occupy a strategic place in the design of a new chemical process. To be qualified as a green medium, a solvent should meet different criteria such as availability, non-toxicity, biodegradability, recyclability, flammability, and low price. An alternative solution to the use of common organic solvents is represented by deep eutectic solvents (DESs), which are eutectic mixtures of two or more solid components, having a lower freezing point than those of the single constituents due to the formation of a thick network of hydrogen bonds. Their straightforward zero-waste synthesis, the possibility of using inexpensive and environmentally benign components, and their unique physicochemical properties like low volatility and high thermal stability make DESs extremely appropriate for many applications. DESs have been employed as green solvents for cross-coupling reactions, whereas, to the best of our knowledge, only two examples of direct arylation (DA) processes were reported in the literature so far. Herein, an optimized protocol for the Pd-catalyzed direct arylation of 3,4-ethylenedioxythiophene (EDOT) and other substituted thiophenes with (hetero)aromatic bromides in a deep eutectic solvent made of a mixture of choline chloride/glycerol (1:2) is presented. The coupling reactions have been successfully run under air and in non-anhydrous conditions, using affordable reagents, such as K2CO3 and PdCl2, with a catalyst loading as low as 1 mol %. The adjustment of each reaction component allowed finding robust conditions for the introduction of both electron-poor and electron-rich (hetero)aryl bromides with moderate-to-high yields. The optimized DA procedure in DES can be successfully applied for the simple preparation of conjugated organic compounds with potential applications in optoelectronics, The sustainability of the protocol was established through calculations of green metrics, such as Eco-scale and E-factor, and compared with the literature, when possible.