Aromatic Hydroxylation at a Non-Heme Iron Center: Observed Intermediates and Insights into the Nature of the Active Species
Aromatic Hydroxylation at a Non-Heme Iron Center: Observed Intermediates and Insights into the Nature of the Active Species
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DOI：
10.1002/chem.201002577
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Rybak-Akimova, Elena V.
中科院分区：
文献类型：
--
作者：
Makhlynets, Olga V.;Rybak-Akimova, Elena V.
阐明了在高反应性仿生铁氨基吡啶络合物 [Fe-II(bpmen)(CH3CN)(2)][ClO4](2) (1; bpmen = N,N'-二甲基-N,N'-双(2-吡啶基甲基)乙烷-1,2-二胺)存在下用过氧化氢进行底物氧化的机制。配合物 1 已被证明是使用 H2O2 进行环氧化和官能团定向芳香族羟基化的优异催化剂，尽管其作用机制仍然很大程度上未知。([1,2]) 在 1 存在的情况下，未官能化苯和取代苯与 H2O2 的有效分子间羟基化反应被发现。报告了铁(III)酚盐产物形成的详细机理研究。我们已经鉴定、高产率生成并通过实验表征了由 1. 和 H2O2 形成的关键 Fe-III(OOH) 中间体（lambda(max)=560 nm，菱形 EPR 信号，g=2.21, 2.14, 1.96），停流动力学研究表明 Fe-III(OOH) 不会直接羟基化芳环，而是进行限速自分解，产生瞬时活性氧化剂。氢过氧化铁中间体中 O-O 键的酸辅助裂解促进了活性物质的形成。 1 和机械探针 2-甲基-1-苯基-2-丙基氢过氧化物 (MPPH) 的酸辅助苯羟基化与 O-O 键杂解相关。独立生成的 Fe-IV=O 物种可能源自 Fe-III(OOH) 中的 O-O 键均裂，已被证明对芳香族底物不具有活性。源自 1 的活性氧化剂与水交换其氧原子并亲电攻击芳环（产生 0.8 的逆 H/D 动力学同位素效应）。这些结果基于中间体和产物的直接表征以及各个反应步骤的动力学分析，揭示了 1 催化的氧化反应的详细实验机理图。我们对该反应机理的详细了解揭示了合成和酶促芳香族羟基化反应之间的相似性和差异。
Mechanism of substrate oxidations with hydrogen peroxide in the presence of a highly reactive, biomimetic, iron aminopyridine complex, [Fe-II(bpmen)(CH3CN)(2)][ClO4](2) (1; bpmen = N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)ethane-1,2-diamine), is elucidated. Complex 1 has been shown to be an excellent catalyst for epoxidation and functional-group-directed aromatic hydroxylation using H2O2, although its mechanism of action remains largely unknown.([1,2]) Efficient intermolecular hydroxylation of unfunctionalized benzene and substituted benzenes with H2O2 in the presence of 1 is found in the present work. Detailed mechanistic studies of the formation of iron(III) phenolate products are reported. We have identified, generated in high yield, and experimentally characterized the key Fe-III(OOH) intermediate (lambda(max)=560 nm, rhombic EPR signal with g=2.21, 2.14, 1.96) formed by 1. and H2O2, Stopped-flow kinetic studies showed that Fe-III(OOH) does not directly hydroxylate the aromatic rings, but undergoes rate-limiting self-decomposition producing transient reactive oxidant. The formation of the reactive species is facilitated by acid-assisted cleavage of the O-O bond in the iron hydroperoxide intermediate. Acid-assisted benzene hydroxylation with 1 and a mechanistic probe, 2-Methyl-1-phenyl-2-propyl hydroperoxide (MPPH), correlates with O-O bond heterolysis. Independently generated Fe-IV=O species, which may originate from O-O bond homolysis in Fe-III(OOH), proved to be inactive toward aromatic substrates. The reactive oxidant derived from 1 exchanges its oxygen atom with water and electrophilically attacks the aromatic ring (giving rise to an inverse H/D kinetic isotope effect of 0.8). These results have revealed a detailed experimental mechanistic picture of the oxidation reactions catalyzed by 1, based on direct characterization of the intermediates and products, and kinetic analysis of the individual reaction steps. Our detailed understanding of the mechanism of this reaction revealed both similarities and differences between synthetic and enzymatic aromatic hydroxylation reactions.