Copper-mediated arylation reactions of potassium thioacetate. Synthesis of aryl thioacetates

SILVIA M. SORIA CASTRO; ALICIA B. PEÑÉÑORY

Campinas

Congreso; Advanced School on Natural Products, Medicinal Chemistry and Organic Synthesis; 2011

Copper-mediated Arylation Reactions of Potassium Thioacetate. Synthesis of Aryl Thioacetates. Aromatic sulfur compounds are relevant in chemical, pharmaceutical and materials industries; in consequence the development of new methodologies for CAr-S bond formation continues being a challenge in organic chemistry. The formation of C-S bonds can be accomplished from good to excellent yields by transition metal catalysis, using, mainly salts from Pd, Cu , Ni and Fe . Cu- or Fe-mediated coupling reactions have become a convenient alternative to the expensive Pd/ligand systems due to the former’s lower cost, stability and ready availability of the ligands. We here in report a convenient methodology for the synthesis of thioesters using Cu-catalysis to mediate the C-S bond formation, which imply the reactions of KSCOMe (1) with aryl iodides under a Cu/ligand system to afford S-aryl thioacetates (2) in good to excellent yields. Initially, we determined the optimal conditions (solvent, temperatura, copper/ligand) for the model reaction of IPh with 1. This coupling reaction did not occur under air or in the absence of the ligand and was improved to 96% yield by using 10 and 20 mol% of CuI salt and 1,10-phenanthroline as ligand, respectively, in toluene at 100ºC for 24h. A variety of commercially available ArI were subject to the optimized reaction conditions to determine the scope of this catalytic system for the synthesis of 2. The coupling of ion 1 with ArI bearing electron-withdrawing and electron-donor groups proceeded in good to excellent isolated or GC-quantified yields (71-96%). For instance, the para-MeO and the para-COMe phenyl iodides afforded thioacetates 2 in 76% and 89% isolated yield, respectively. Furthermore, sterically hindered ortho-Me and ortho-OMe aryl iodides rendered 84 and 76% yields, respectively, of the coupling products 2. In conclusion, we have developed a simple, efficient and economically attractive procedure for the synthesis of S-aryl thioacetates. This protocol reports a novel C-S bond formation by Cu-catalysis as a convenient alternative for obtaining sulfur compounds. Electron-donor and electron-acceptor substituents are tolerated, and polysubstitution can also be accomplished.