区分Cu2O2介导的氧化N-脱烷基反应中限速电子转移与氢原子转移：分子间与分子内动力学同位素效应的应用

Distinguishing rate-limiting electron versus H-atom transfers in Cu2O2-mediated oxidative N-dealkylations: application of inter- versus intramolecular kinetic isotope effects.

作者信息

Shearer Jason, Zhang Christiana Xin, Hatcher Lanying Q, Karlin Kenneth D

机构信息

Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.

出版信息

J Am Chem Soc. 2003 Oct 22;125(42):12670-1. doi: 10.1021/ja0359409.

DOI:10.1021/ja0359409

PMID:14558790

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)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.

摘要

铜-双氧加合物是重要的生物氧化剂。为了更好地理解这类物质的潜在化学性质，我们报道了一系列Cu₂⁺-O₂配合物，{Cu²⁺(MePY₂)R'}₂(O₂)₂ (1R')（其中(MePY₂)R'是4-吡啶基取代的双[2-(2-(4-R'-吡啶基)乙基]甲胺；R' = H、甲氧基、二甲氨基；Zhang, C. X.等人，《美国化学会志》2003年，125卷，634 - 635页），它们能轻易氧化外源底物。在本研究中，我们探究了1R'促进对位取代的N,N-二甲基苯胺（R-DMA；R = 甲氧基、甲基、氢、氰基）氧化N-脱烷基化的机制。对于1H，线性自由能相关图（ρ = -2.1）和分子内氘动力学同位素效应（KIEintra，使用对-R-(C₆H₄)-N(CH₃)(CD₃)）曲线表明，R-DMA氧化是通过限速电子转移（ET）发生。通过比较KIEintra与分子间KIE（KIEinter，使用对-R-(C₆H₄)-N(CH₃)₂与对-R-(C₆H₄)-N(CD₃)₂），进一步证实了该机制。发现KIEinter < KIEintra，表明是一个ET过程。对于1MeO和1Me₂N，KIEintra曲线和线性自由能相关图（1Me₂N和1MeO的ρ分别为 -0.49和 -0.99，后者拟合效果特别差）在区分限速ET或氢原子转移（HAT）途径方面尚无定论。KIEinter与KIEintra的比较表明，随着R-DMA还原性降低，1Me₂N和1MeO氧化R-DMA的机制从ET转变为HAT。对于1Me₂N，甲氧基-DMA和甲基-DMA通过限速ET被氧化（KIEinter < KIEintra），而氢-DMA和氰基-DMA通过HAT途径被氧化（KIEinter ≈ KIEintra）。对于1MeO，甲氧基-DMA、甲基-DMA和氢-DMA通过ET途径被氧化（KIEinter < KIEintra），而氰基-DMA通过HAT过程被氧化（KIEinter ≈ KIEintra）。文中提出了可能导致这些机制观察结果的铜配合物属性。