aerobic Catalysis
Molecular oxygen (O2) is an ideal reagent for chemical synthesis. It is innocuous, naturally occurring and energetic, and can provide a strong driving force for otherwise challenging transformations. The production of H2O as the byproduct of its reduction provides an additional benefit to the environmental impact of aerobic oxidations.
Despite these attractive features, O2 remains underutilized in fine and pharmaceutical synthesis due to issues of selectivity. O2 is prone to radical reactions that can be difficult to control, particularly in complex settings where there are often multiple sites of potential oxidation, and issues of regio- and stereoselectivity are paramount.
To address these challenges, we draw inspiration from metalloenzymes, which activate and utilize O2 with unparalleled levels of control. Our research program attempts to mimic the active sites of these enzymes with simple catalyst components, so as to harness biosynthetic pathways for the utilization of O2 under operationally simple conditions. By bringing O2 into the coordination sphere of transition metals, we place this otherwise unruly reagent into the confines of well-defined organometallic complexes, where its steric and electronic properties can be finely tuned.
Using this approach, our group has developed small-molecule mimics of the enzymes tyrosinase, copper-amine oxidase and galactose oxidase, and employed these mimics in selective oxidations of phenols, catechols, alcohols and amines. On-going projects include the application of these catalyst platforms to synthetic challenges in fine and pharmaceutical synthesis, as well as new catalyst development to effect novel transformations.
Representative Publications
1) Esguerra, K. V. N.; Lumb, J.-P. “Selectivity in the Aerobic Dearomatization of Phenols: Total Synthesis of Dehydronornuciferine by Chemo- and Regioselective Oxidation.” Angew. Chemie Int. Ed. 2018, 57, 1514-1518.
2) Huang, Z.; Lumb, J.-P. “A Catalyst-Controlled Aerobic Coupling of ortho-Quinones and Phenols Applied to the Synthesis of Aryl Ethers.” Angew. Chemie. Int. Ed. 2016, 55, 11543-11547.
3) Esguerra, K. V. N.; Fall, Y.; Petitjean, L.; Lumb, J.-P. “Controlling the Catalytic Aerobic Oxidation of Phenols.” J. Am. Chem. Soc. 2014, 136, 7662-7668.
4) Xu, B.; Hartigan, E.; Feula, G.; Huang, Z.; Lumb, J.-P.; Arndtsen, B. “Simple Copper Catalysts for the Aerobic Oxidation of Amines: Selectivity Control by the Counterion.” Angew. Chemie Int. Ed. 2016, 55, 15802-15806.
5) McCann, S.; Lumb, J.-P.; Arndtsen, B.; Stahl, S. “Second-Order Biomimicry: In Situ Oxidative Self-Processing Converts Copper(I)/Diamine Precursor into a Highly Active Aerobic Oxidation Catalyst.” ACS Central Sci. 2017, 3, 314-321.