Influence of the Ligand of Palladium(0) Complexes on the Rate of the Oxidative Addition of Aryl and Activated Alkyl Bromides: Csp2-Br versus Csp3-Br Reactivity and Selectivity

Kinetic data obtained by means of electrochemical techniques are used to characterize the reactivity of aryl bromides and activated alkyl bromides in the oxidative addition to palladium(0) complexes generated from three precursors: Pd-0(PPh3)(4), {Pd-0(dba)(2)+ 2PPh(3)} (dba=dibenzylideneacetone) and {Pd-0(dba)(2)+ 2P(o-Tol)(3)} in dimethylformamide (DMF) at 25 degrees C. It is established that, for the investigated substrates 1-6 and 7-11, the oxidative addition at the Csp(3)-Br bond is much faster than that at the Csp(2)-Br bond if the palladium(0) is ligated by two PPh3. This explains why the regioselectivity in Suzuki-Miyaura reactions performed from substrates bearing both Csp(2)-Br and Csp(3)-Br groups is in favor of the substitution at the Csp(3)-Br bond. This is in agreement with DFT calculations, which propose a SN2-type mechanism from the bis-ligated Pd-0(PPh3)(2). The oxidative addition at the Csp(2)-Br bond is much faster if the palladium(0) is ligated by P(o-Tol)(3) than by PPh3, in agreement with the DFT calculations, which support a concerted mechanism involving the mono-ligated Pd-0[P(o-Tol)(3)] as the reactive species. This explains why the regioselectivity in Suzuki-Miyaura reactions performed from substrates bearing both Csp(2)-Br and Csp(3)-Br groups might be in favor of the substitution at the Csp(2)-Br bond if the ligand is P(o-Tol)(3).