A greener approach to Buchwald-Hartwig coupling. A sustainable Pd/C-catalyzed Csp2–N bond formation under microwave irradiation and bio-based solvent

The Buchwald-Hartwig coupling enables the grafting of nitrogen-containing functionalities onto molecules, facilitating the synthesis of a wide variety of molecular structures. However, several challenges impact the sustainability of this coupling. In our pursuit of a more sustainable Buchwald-Hartwig process, we report an optimized protocol that enhances energy efficiency and minimizes waste. Utilizing recoverable Pd/C as a catalyst, we performed the process in the bio-based solvent 2-MeTHF. To further boost energy efficiency, we employed microwave heating technology, resulting in improved overall process efficiency and reduced reaction times. This optimized approach allowed for the synthesis of a wide array of 17 variously functionalized arylamines. Thanks to the optimized workup procedure that facilitated the recovery and reuse of the catalyst, ligand, and 2-MeTHF, we achieved a reduced E-Factor ranging from 5.8 to 14.9, further contributing to the sustainability of the process.