Abstract
In this Account, we describe the transition metal-mediated cleavage of C−F and C−H bonds in fluoroaromatic and fluoroheteroaromatic molecules. The simplest reactions of perfluoroarenes result in C−F oxida tive addition, but C−H activation competes with C−F activation for partially fluorinated molecules. We first consider the reactivity of the fluoroaromatics toward nickel and platinum complexes, but extend to rhenium and rhodium where they give special insight. Sections on spectroscopy and molecular structure are followed by discussions of energetics and mechanism that incorporate experimental and computational results. We highlight special characteristics of the metal−fluorine bond and the influence of the fluorine substituents on energetics and mechanism. Fluoroaromatics reacting at an ML2 center initially yield η2-arene complexes, followed usually by oxidative addition to generate MF(ArF)(L)2 or MH(ArF)(L)2 (M is Ni, Pd, or Pt; L is trialkylphosphine). The outcome of competition between C−F and C−H bond activation is strongly metal dependent and regioselective. When C−H bonds of fluoroaromatics are activated, there is a preference for the remaining C−F bonds to lie ortho to the metal. An unusual feature of metal−fluorine bonds is their response to replacement of nickel by platinum. The Pt−F bonds are weaker than their nickel counterparts; the opposite is true for M−H bonds. Metal−fluorine bonds are sufficiently polar to form M−F***H−X hydrogen bonds and M−F***I−C6F5 halogen bonds. In the competition between C−F and C−H activation, the thermodynamic product is always the metal fluoride, but marked differences emerge between metals in the energetics of C−H activation. In metal−fluoroaryl bonds, ortho-fluorine substituents generally control regioselectivity and make C−H activation more energetically favorable. The role of fluorine substituents in directing C−H activation is traced to their effect on bond energies. Correlations between M−C and H−C bond energies demonstrate that M−C bond energies increase far more on ortho-fluorine substitution than do H−C bonds. Conventional oxidative addition reactions involve a three-center triangular transition state between the carbon, metal, and X, where X is hydrogen or fluorine, but M(d)−F(2p) repulsion raises the activation energies when X is fluorine. Platinum complexes exhibit an alternative set of reactions involving rearrangement of the phosphine and the fluoroaromatics to a metal(alkyl)(fluorophosphine), M(R)(ArF)(PR3)(PR2F). In these phosphine-assisted C−F activation reactions, the phosphine is no spectator but rather is intimately involved as a fluorine acceptor. Addition of the C−F bond across the M−PR3 bond leads to a metallophosphorane four-center transition state; subsequent transfer of the R group to the metal generates the fluorophosphine product. We find evidence that a phosphine-assisted pathway may even be significant in some apparently simple oxidative addition reactions. While transition metal catalysis has revolutionized hydrocarbon chemistry, its impact on fluorocarbon chemistry has been more limited. Recent developments have changed the outlook as catalytic reactions involving C−F or C−H bond activation of fluorocarbons have emerged. The principles established here have several implications for catalysis, including the regioselectivity of C−H activation and the unfavorable energetics of C−F reductive elimination. Palladium-catalyzed C−H arylation is analyzed to illustrate how ortho-fluorine substituents influence thermodynamics, kinetics, and regioselectivity.