Copper-Free Heck−Cassar−Sonogashira and Suzuki−Miyaura Reactions of Aryl Chlorides: A Sustainable Approach

Sustainable and efficient aryl halides with copper free Heck−Cassar−Sonogashira (HCS) and Suzuki−Miyaura (SM) cross-coupling reactions were described. Independently from the aryl chloride substituents, the green protocol based on N-hydroxyethylpyrrolidone (HEP)/water as solvents and sodium 2′-dicyclohexylphosphino-2,6-dimethoxy-1,1′-biphenyl-3-sulfonate (sSPhos) as ligand afforded the target products with a high turnover number (TON), high reaction mass efficiency (RME), and low process mass intensity (PMI). The best results have been obtained with TMG and Cs2CO3 as the base for the HCS and Cs2CO3 and K2CO3 for the SM coupling. The PMI and RME achieved are among the best in the field and allowed us to simplify purification processes that are critical for industrial applications.