Bimetallic Redox Synergy in Oxidative Palladium Catalysis

Polynuclear transition metal complexes, which are embedded in the active sites of many metalloenzymes, are responsible for effecting a diverse array of oxidation reactions in nature. The range of chemical transformations remains unparalleled in the laboratory. With few noteworthy exceptions, chemists have primarily focused on mononuclear transition metal complexes in developing homogeneous catalysis. Our group is interested in the development of carbon-heteroatom bond-forming reactions, with a particular focus on identifying reactions that can be applied to the synthesis of complex molecules. In this context, we have hypothesized that bimetallic redox chemistry, in which two metals participate synergistically, may lower the activation barriers to redox transformations relevant to catalysis. In this Account, we discuss redox chemistry of binuclear Pd complexes and examine the role of binudear intermediates in Pd-catalyzed oxidation reactions. Stoichiometric organometallic studies of the oxidation of binuclear Pd-II complexes to binuclear Pd-III complexes and subsequent C-X reductive elimination from the resulting binudear Pd-III complexes have confirmed the viability of C-X bond-forming reactions mediated by binuclear Pd-III complexes. Metal metal bond formation, which proceeds concurrently with oxidation of binuclear Pd-II complexes, can lower the activation barrier for oxidation. We also discuss experimental and theoretical work that suggests that C-X reductive elimination is also facilitated by redox cooperation of both metals during reductive elimination. The effect of ligand modification on the structure and reactivity of binuclear Pd-III complexes will be presented in light of the impact that ligand structure can exert on the structure and reactivity of binudear Pd-III complexes. Historically, oxidation reactions similar to those discussed here have been proposed to proceed via mononudear Pd-IV intermediates, and the hypothesis of mononuclear Pd-II/IV catalysis has guided the successful development of many reactions. Herein we discuss differences between monometallic Pd-IV and bimetallic Pd-III redox catalysis. We address whether appreciation of the relevance of bimetallic Pd-III redox catalysis is of academic interest exclusively, serving to provide a more nuanced description of catalysis, or if the new insight regarding bimetallic Pd-III chemistry can be a platform to enable future reaction development. To this end, we describe an example in which the hypothesis of bimetallic redox chemistry guided reaction development, leading to the discovery of reactivity distinct from monometallic catalysts.