title: A Biomimetic Mechanism for the Copper-Catalyzed Aerobic Oxygenation of 4-tert-Butylphenol.
abstract: Controlling product selectivity during the catalytic aerobic oxidation of phenols remains a significant challenge that hinders reaction development. This work provides a mechanistic picture of a Cu-catalyzed, aerobic functionalization of phenols that is selective for phenoxy-coupled ortho-quinones. We show that the immediate product of the reaction is a Cu(II)-semiquinone radical complex and reveal that ortho-oxygenation precedes oxidative coupling. This complex is the resting state of the Cu catalyst during turnover at room temperature. A mechanistic study of the formation of this complex at low temperatures demonstrates that the oxygenation pathway mimics the dinuclear Cu enzyme tyrosinase by involving a dinuclear side-on peroxodicopper(II) oxidant. Unlike the enzyme, however, the rate-limiting step of the ortho-oxygenation reaction is the self-assembly of the oxidant from Cu(I) and O2. We provide details for all steps in the cycle and demonstrate that turnover is contingent upon proton-transfer events that are mediated by a slight excess of ligand. Finally, our knowledge of the reaction mechanism can be leveraged to diversify the reaction outcome. Thus, uncoupled ortho-quinones are favored in polar, coordinating media, highlighting unusually high levels of chemoselectivity for a catalytic aerobic oxidation of a phenol.
authors: Department of Chemistry and Biochemistry, Concordia University , Montreal, QC H4B 1R6, Canada.
authors: Mohammad S
authors: MS
authors: Askari
authors: Department of Chemistry, McGill University , Montreal, QC H3A 0B8, Canada.
authors: Kenneth Virgel N
authors: KV
authors: Esguerra
authors: Department of Chemistry, McGill University , Montreal, QC H3A 0B8, Canada.
authors: Jean-Philip
authors: JP
authors: Lumb
authors: Department of Chemistry and Biochemistry, Concordia University , Montreal, QC H4B 1R6, Canada.
authors: Xavier
authors: X
authors: Ottenwaelder
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*
chemical_list: D010636:Phenols; D003300:Copper; D014442:Monophenol Monooxygenase; C006862:butylphen; D010100:Oxygen