title: Amine oxidative N-dealkylation via cupric hydroperoxide Cu-OOH homolytic cleavage followed by site-specific fenton chemistry.
abstract: Copper(II) hydroperoxide species are significant intermediates in processes such as fuel cells and (bio)chemical oxidations, all involving stepwise reduction of molecular oxygen. We previously reported a Cu(II)-OOH species that performs oxidative N-dealkylation on a dibenzylamino group that is appended to the 6-position of a pyridyl donor of a tripodal tetradentate ligand. To obtain insights into the mechanism of this process, reaction kinetics and products were determined employing ligand substrates with various para-substituent dibenzyl pairs (-H,-H; -H,-Cl; -H,-OMe, and -Cl,-OMe), or with partially or fully deuterated dibenzyl N-(CH2Ph)2 moieties. A series of ligand-copper(II) bis-perchlorate complexes were synthesized, characterized, and the X-ray structures of the -H,-OMe analogue were determined. The corresponding metastable Cu(II)-OOH species were generated by addition of H2O2/base in acetone at -90 °C. These convert (t1/2 ≈ 53 s) to oxidatively N-dealkylated products, producing para-substituted benzaldehydes. Based on the experimental observations and supporting DFT calculations, a reaction mechanism involving dibenzylamine H-atom abstraction or electron-transfer oxidation by the Cu(II)-OOH entity could be ruled out. It is concluded that the chemistry proceeds by rate limiting Cu-O homolytic cleavage of the Cu(II)-(OOH) species, followed by site-specific copper Fenton chemistry. As a process of broad interest in copper as well as iron oxidative (bio)chemistries, a detailed computational analysis was performed, indicating that a Cu(I)OOH species undergoes O-O homolytic cleavage to yield a hydroxyl radical and Cu(II)OH rather than heterolytic cleavage to yield water and a Cu(II)-O(•-) species.
authors.affiliation: Department of Chemistry, Johns Hopkins University , Baltimore, Maryland 21218, United States.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Kim
authors.forename: Jake W
authors.initials: JW
authors.lastname: Ginsbach
authors.forename: Jung Yoon
authors.initials: JY
authors.lastname: Lee
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Peterson
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Liu
authors.forename: Maxime A
authors.initials: MA
authors.lastname: Siegler
authors.forename: Amy A
authors.initials: AA
authors.lastname: Sarjeant
authors.forename: Edward I
authors.initials: EI
authors.lastname: Solomon
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Karlin
mesh_terms: D000588:Amines / Q000737:chemistry*; D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D003640:Dealkylation; D006861:Hydrogen Peroxide / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry*
chemical_list: D000588:Amines; C045076:Fenton's reagent; D010545:Peroxides; D017665:Hydroxyl Radical; D003300:Copper; D006861:Hydrogen Peroxide; D007501:Iron