Mechanistic Organometallic Studies Drive Reagent Selection and Catalyst Design for the Palladium-Catalyzed Trifluoromethylthiolation of Aryl Electrophiles.

This article describes a detailed investigation of the palladium-catalyzed coupling of aryl (pseudo)halides (ArX) with MSCF to form aryl trifluoromethylthioethers (ArSCF). Mechanistic organometallic studies are used to interrogate two key elementary steps of the catalytic cycle: (1) transmetalation of Pd(Ar)(X) complexes with MSCF and (2) Ar-SCF bond-forming reductive elimination. These studies reveal that tetramethylammonium trifluoromethylthiolate, NMeSCF, exhibits a combination of fast kinetics and high chemoselectivity for transmetalation. Furthermore, Ar-SCF reductive elimination is fastest and highest yielding with 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XantPhos), di-butylphosphinoferrocene (D BuPF), and tri--butylphosphine (P Bu) as ligands. These results are leveraged to develop a palladium-catalyzed method for coupling aryl iodides, -bromides, and -triflates with NMeSCF using catalytic Pd(dba) and D BuPF. This transformation exhibits a broad substrate scope and offers several advantages over state-of-the-art Pd-catalyzed methods for aryl-SCF coupling.