Thermal Nickel-Catalyzed <i>N</i>-Arylation of NH-Sulfoximines with (Hetero)aryl Chlorides Enabled by PhPAd-DalPhos Ligation
Samuel A. Fisher, Connor M. Simon, Peter L. Fox, Michael J. Cotnam, Patrick DeRoy, Mark Stradiotto
Abstract
We report a versatile method for cross-coupling of NH -sulfoximines with (hetero)aryl chlorides, as well as bromide and sulfonate electrophiles, that makes use of the air-stable, commercial precatalyst (PhPAd-DalPhos)Ni( o -tol)Cl. Under optimized conditions a diverse electrophile scope is established, including the N -arylation of the pharmaceutical Clozapine. While 5 mol % Ni and 80 °C are commonly employed in this chemistry, successful examples utilizing 1 mol % Ni and/or 25 °C are presented. Competition experiments establish the superiority of NH -sulfoximine over primary sulfonamide as nucleophiles under these conditions.
Topics & Concepts
ChemistryElectrophileArylNucleophileSulfonamideBromideCatalysisCombinatorial chemistryNickelSulfonateMedicinal chemistryOrganic chemistrySodiumAlkylSynthesis and Catalytic ReactionsCatalytic C–H Functionalization MethodsSulfur-Based Synthesis Techniques