Cu-Catalyzed Coupling Reactions Of Aryl Halides With Sulfonamides/NH-Sulfoximines

Transition-metal-catalyzed cross-coupling is one of the most important tools for the synthesis of complex molecules because of its versatility and reliability in the formation of carbon-carbon and carbon-heteroatom bonds.Among them,Cucatalyzed Ullmann-type cross-coupling has received substantial attention due to its low cost,low toxicity,and more importantly wide scope of transformations.During the past years,some oxalamides were more powerful ligands than amino acids,diamines,phenanthrolines and 8-hydroxyquinolines previously applied in Cu-catalyzed coupling between(hetero)aryl halides and nucleophiles.These oxalamide ligands not only enabled coupling of(hetero)aryl bromides and iodides at lower catalytic loadings and reaction temperatures,but also made coupling of less reactive(hetero)aryl chlorides possible under relatively mind conditions.As a continuous effort,we have demonstrated that the combination of copper salts and some oxalamides(or hydroxypicolinamides)could catalyze sulfonamidation of(hetero)aryl halides,as well as N-arylation of NH-sulfoximines with(hetero)aryl halides.Direct N-arylation of sulfonamides is a very attractive approach for preparing pharmaceutically important N-(hetero)aryl sulfonamides because it avoids the potential genotoxic problem resulting from the previous condensation method.Most known catalytic methods suffer from limited reaction scope and inconveniency on metal catalyst and ligand availability.Here we described that the combination of copper and oxalamides(or 4-hydroxypicolinamides)offers a powerful catalytic system for N-arylation of sulfonamides.A wide range of primary and secondary sulfonamides were able to couple with a series of(hetero)aryl bromides in the presence of 2-5 mol%copper salts and oxalamides at 100 ℃.Coupling of primary sulfonamides with(hetero)aryl chlorides worked well under the catalysis of Cu2O and a 4-hydroxypicolinamide.The catalytic method enabled direct sulfonamidation of four chlorocontaining marketed drugs and preparation of two sulfonamide drugs from the corresponding aryl halides.N-(hetero)arylsulfoximines have attracted much attention in organic chemistry due to the fact that various derivatives showed anticancer activity or proved applicable as agrochemicals.As a result,significant efforts have been devoted to the development of effective strategies towards the N-arylation of sulfoximines.We have demonstrated that Cu/oxalamide-catalyzed coupling of(hetero)aryl bromides with NH-sulfoximines proceeded smoothly at low catalytic loadings and reaction temperatures to afford a variety of N-(hetero)aryl sulfoximines.Our studies not only provide a less expensive and readily accessible catalytic system,but also offer a solution for coupling with electron-rich(hetero)aryl bromides,expanding the substrate scope significantly.