Small Phosphine Ligands Enable Selective Oxidative Addition of Ar–O over Ar–Cl Bonds at Nickel(0)

Current methods for Suzuki-Miyaura couplings of nontriflate phenol derivatives are limited by their intolerance of halides including aryl chlorides. This is because Ni(0) and Pd(0) often undergo oxidative addition of organohalides at a similar or faster rate than most Ar–O bonds. DFT and stoichiometric oxidative addition studies demonstrate that small phosphines, in particular PMe3, are unique in promoting preferential reaction of Ni(0) with aryl tosylates and other C–O bonds in the presence of aryl chlorides. This selectivity was exploited in the first Ni-catalyzed C–O-selective Suzuki-Miyaura coupling of chlorinated phenol derivatives where the oxygen-containing leaving group is not a fluorinated sulfonate such as triflate. Computational studies suggest that the origin of divergent selectivity between PMe3 and other phosphines differs from prior examples of ligand-controlled chemodivergent cross-couplings. PMe3 effects selective reaction at tosylate due to both electronic and steric factors. A close interaction between nickel and a sulfonyl oxygen of tosylate during oxidative addition is critical to the observed selectivity.