title: Distinguishing rate-limiting electron versus H-atom transfers in Cu2O2-mediated oxidative N-dealkylations: application of inter- versus intramolecular kinetic isotope effects.
abstract: Copper-dioxygen adducts are important biological oxidants. To gain a better understanding of the underlying chemistries of such species, we report on a series of Cu2II-O2 complexes, [{CuII(MePY2)R'}2(O2)](B(C6F5)4)2 (1R') (where (MePY2)R' is a 4-pyridyl substituted bis[2-(2-(4-R'-pyridyl)ethyl]methylamine; R' = H, MeO, Me2N; Zhang, C. X.; et al. J. Am. Chem. Soc. 2003, 125, 634-635), which readily oxidize exogenous substrates. In this study, we explore the mechanism by which 1R' facilitates the oxidative N-dealkylation of para-substituted N,N-dimethylanilines (R-DMA; R = MeO, Me, H, CN). In the case of 1H, the linear free-energy correlation plot (rho = -2.1) and intramolecular deuterium kinetic isotope effect (KIEintra, using p-R-(C6H4)-N(CH3)(CD3)) profile suggest that R-DMA oxidation occurs through rate-limiting electron transfer (ET). This mechanism was further enforced by comparison of KIEintra versus the intermolecular KIE (KIEinter, using p-R-(C6H4)-N(CH3)2 versus p-R-(C6H4)-N(CD3)2). It was found that KIEinter < KIEintra, suggesting an ET process. In the case of both 1MeO and 1Me2N, the KIEintra profile and linear free-energy correlation plots (rho = -0.49 and -0.99 for 1Me2N and 1MeO with especially poor fitting for the latter) are inconclusive in distinguishing between a rate-limiting ET or hydrogen atom transfer (HAT) pathway. Comparisons of KIEinter versus KIEintra demonstrate a switch in mechanism from ET to HAT for 1Me2N and 1MeO oxidation of R-DMA as R-DMA is made less reducing. In the case of 1Me2N, MeO-DMA and Me-DMA are oxidized via a rate-limiting ET (KIEinter < KIEintra), while H-DMA and CN-DMA are oxidized through a HAT pathway (KIEinter approximately KIEintra). For 1MeO, oxidation occurs through an ET pathway for MeO-, Me-, and H-DMA (KIEinter < KIEintra), while CN-DMA is oxidized though a HAT process (KIEinter approximately KIEintra). Copper complex attributes, which may contribute to the mechanistic observations, are suggested.
authors.affiliation: Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA. karlin@jhu.edu
authors.forename: Jason
authors.initials: J
authors.lastname: Shearer
authors.forename: Christiana Xin
authors.initials: CX
authors.lastname: Zhang
authors.forename: Lanying Q
authors.initials: LQ
authors.lastname: Hatcher
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Karlin
mesh_terms: D000478:Alkylation; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004583:Electrons; D006859:Hydrogen / Q000737:chemistry; D007700:Kinetics; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*
chemical_list: D000814:Aniline Compounds; C015157:N,N-dimethylaniline; D003300:Copper; D006859:Hydrogen; D010100:Oxygen; C021313:methylaniline; C030973:cupric oxide