Catalytic Carbon−Halogen Bond Activation:  Trends in Reactivity, Selectivity, and Solvation

We have theoretically studied the oxidative addition of all halomethanes CH₃X (with X = F, Cl, Br, I, At) to Pd and PdCl^-, using both nonrelativistic and zeroth-order-regular-approximation-relativistic density functional theory at BLYP/QZ4P. Our study covers the gas phase as well as the condensed phase (water), where solvent effects are described with the conductor-like screening model. The activation of the C*−X bond may proceed via two stereochemically different pathways:  (i) direct oxidative insertion (OxIn) which goes with retention of the configuration at C* and (ii) an alternative S_N2 pathway which goes with inversion of the configuration at C*. In the gas phase, for Pd, the OxIn pathway has the lowest reaction barrier for all CH₃X's. Anion assistance, that is, going from Pd to PdCl^-, changes the preference for all CH₃X's from OxIn to the S_N2 pathway. Gas-phase reaction barriers for both pathways to C−X activation generally decrease as X descends in group 17. Two striking solvent effects are (i) the shift in reactivity of Pd + CH₃X from OxIn to S_N2 in the case of the smaller halogens, F and Cl, and (ii) the shift in reactivity of PdCl^- + CH₃X in the opposite direction, that is, from S_N2 to OxIn, in the case of the heavier halogens, I and At. We use the activation strain model to arrive at a qualitative understanding of how the competition between OxIn and S_N2 pathways is determined by the halogen atom in the activated C−X bond, by anion assistance, and by solvation.