Aerobic Oxidation Catalysis

There is a dramatic need for environmentally benign oxidation chemistry in the pharmaceutical and chemical industries. Molecular oxygen represents an ideal alternative to commonly used stoichiometric oxidants such as CrO42- and MnO4; however, the scope of dioxygen-coupled oxidation reactions is presently quite limited. Our research has been focused on the development and mechanistic characterization of “organometallic oxidase” reactions. Over the past ten years, this class of oxidation reactions has become the most versatile approach for selective aerobic oxidation of organic molecules. Reactions of this type enable selective dehydrogenation (e.g., alcohol oxidation), oxidative carbonylation, and C-H functionalization, including C-C, C-O and C-N bond-forming reactions.

The “oxidase” term reflects the fact that these reactions proceed by a two-stage catalytic cycle that resembles the mechanism of biological oxidases (see graphic). The two stages of the catalytic mechanism feature (1) oxidation of an organic molecule by a transition-metal center, such as PdII or CuII, via an organometallic pathway (Stage I) and (2) oxidation of the reduced catalyst by molecular oxygen (Stage II). The mechanistic versatility of organometallic chemistry enables a broad range of oxidative transformations to be achieved with molecular oxygen as the stoichiometric oxidant.

Organometallic oxidase reactions represent the consummate “playground” for chemists with an interest in synthetic and/or mechanistic organometallic, organic and inorganic chemistry, and for those who seek to have an impact on environmentally responsible chemical synthesis. Advances in the synthetic applications of these reactions are closely linked to the elucidation of new fundamental principles of chemical reactivity, for example, new organometallic transformations and reactions of molecular oxygen with transition metal centers. Our group has several active projects in this area:

  1. Development of Pd- and Cu-catalyzed synthetic methods for aerobic oxidative functionalization of alkenes and C-H bonds
  2. Elucidation of catalytic mechanisms of Pd- and Cu-catalyzed organometallic oxidase reactions
  3. Investigation of novel organometallic reactions involving Pd and Cu that are relevant to aerobic oxidation methods
  4. Investigation of fundamental reactions between molecular oxygen and transition-metal complexes

Recent Publications:

  1. Ryan, M. C.; Martinelli, J. R.; Stahl, S. S. Cu-Catalyzed Aerobic Oxidative N–N Coupling of Carbazoles and Diarylamines Including Selective Cross-CouplingJ. Am. Chem. Soc. 2018, 140, 9074-9077. DOI:10.1021/jacs.8b05245
  2. Preger, Y.; Root, T. W.; Stahl, S. S. Platinum-Based Heterogenous Catalysts for Nitrile Synthesis via Aerobic Oxidative Coupling of Alcohols and AmmoniaACS Omega 2018, 3, 6091-6096. DOI:10.1021/acsomega.8b00911
  3. Tereniak, S. J.; Landis, C. R.; Stahl, S. S. Are Phosphines Viable Ligands for Pd-Catalyzed Aerobic Oxidation Reactions? Contrasting Insights from a Survey of Six ReactionsACS Catal. 2018, 8, 3708-3714. DOI:10.1021/acscatal.8b01009
  4. Mannel, D. S.; King, J.; Preger, Y.; Ahmed, M. S.; Root, T. W.; Stahl, S. S. Mechanistic Insights into Aerobic Oxidative Methyl Esterification of Primary Alcohols with Heterogeneous PdBiTe CatalystsACS Catal. 2018, 8, 1038-1047. DOI:10.1021/acscatal.7b02886
  5. Tereniak, S. J.; Stahl, S. S. Mechanistic Basis for Efficient, Site-Selective, Aerobic Catalytic Turnover in Pd-Catalyzed C–H Imidoylation of Heterocycle-Containing MoleculesJ. Am. Chem. Soc. 2017, 139, 14533-14541. DOI:10.1021/jacs.7b07359