Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes: Structural, Spectroscopic, and Mechanistic Investigations
Aromatic C-F Hydroxylation by Nonheme Iron(IV)-Oxo Complexes: Structural, Spectroscopic, and Mechanistic Investigations
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DOI：
10.1021/jacs.6b03346
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发表时间：
2016-10-05
影响因子：
15
通讯作者：
Goldberg, David P.
中科院分区：
文献类型：
--
作者：
Sahu, Sumit;Zhang, Bo;Goldberg, David P.
报道了一系列进行分子内芳香族 C-F 羟基化反应的单核非血红素铁配合物的合成和反应性。 C-F 羟基化之前的关键中间体 [Fe-IV(O)(N4Py(2Ar1))](BF4)(2) (1-O, Ar-1 = -2,6-二氟苯基) 通过单晶 X 射线衍射进行了表征。晶体结构揭示了与 CH3CN 分子的非键合 C-H 中心点 O-Fe 相互作用。 1-O 的变场 MAossbauer 光谱表明处于中间自旋 (S = 1) 基态。 1-O 的穆斯堡尔参数包括三重态 FeIV(O) 的异常小的四极分裂，并且通过密度泛函理论计算可以很好地重现。为了研究 C-F 羟基化的初始步骤，合成了两个新配体 N4Py(2Ar2) (L2, Ar-2 = -2,6-二氟-4-甲氧基苯基) 和 N4Py(2Ar3) (L3, Ar3 = -2,6-二氟-3-甲氧基苯基)，在相对于 C-F 键的间位或邻位/对位上具有 -OMe 取代基。 FeII 配合物 [Fe(N4Py(2Ar2))(CH3CN)](ClO4)(2) (2) 和 [Fe(N4Py2(Ar3))(CH3CN)](ClO4)(2) (3) 与 2-碘氧基苯甲酸异丙酯反应，得到 C-F 羟基化 FeIII-OAr 产物。 FeIV(O) 中间体 2-O 和 3-O 在低温下被捕获并进行表征。配合物 2-O 显示出与 1-O 相似的 C-F 羟基化速率。相比之下，复合物 3-O 的动力学（通过停流 UV-vis）显示 C-F 羟基化速率显着增强。 Eyring 分析揭示了三种配合物 C-F 羟基化反应的活化障碍，与观察到的反应性差异一致。独立制备了末端 Fe-II(OH) 配合物 (4)，以研究亲核芳香族取代途径的可能性，但 4 的稳定性排除了这种机制。综合起来，这些数据完全支持亲电 C-F 羟基化机制。
The synthesis and reactivity of a series of mononuclear nonheme iron complexes that carry out intramolecular aromatic C-F hydroxylation reactions is reported. The key intermediate prior to C-F hydroxylation, [Fe-IV(O)(N4Py(2Ar1))](BF4)(2) (1-O, Ar-1 = -2,6-difluorophenyl), was characterized by single-crystal X-ray diffraction. The crystal structure revealed a nonbonding C-H center dot center dot center dot O-Fe interaction with a CH3CN molecule. Variable-field MAossbauer spectroscopy of 1-O indicates an intermediate-spin (S = 1) ground state. The Mossbauer parameters for 1-O include an unusually small quadrupole splitting for a triplet FeIV(O) and are reproduced well by density functional theory calculations. With the aim of investigating the initial step for C-F hydroxylation, two new ligands were synthesized, N4Py(2Ar2) (L2, Ar-2 = -2,6-difluoro-4-methoxyphenyl) and N4Py(2Ar3) (L3, Ar3 = -2,6-difluoro-3-methoxyphenyl), with -OMe substituents in the meta or ortho/para positions with respect to the C-F bonds. FeII complexes [Fe(N4Py(2Ar2))(CH3CN)](ClO4)(2) (2) and [Fe(N4Py2(Ar3))(CH3CN)](ClO4)(2) (3) reacted with isopropyl 2-iodoxybenzoate to give the C-F hydroxylated FeIII-OAr products. The FeIV(O) intermediates 2-O and 3-O were trapped at low temperature and characterized. Complex 2-O displayed a C-F hydroxylation rate similar to that of 1-O. In contrast, the kinetics (via stopped-flow UV-vis) for complex 3-O displayed a significant rate enhancement for C-F hydroxylation. Eyring analysis revealed the activation barriers for the C-F hydroxylation reaction for the three complexes, consistent with the observed difference in reactivity. A terminal Fe-II(OH) complex (4) was prepared independently to investigate the possibility of a nucleophilic aromatic substitution pathway, but the stability of 4 rules out this mechanism. Taken together the data fully support an electrophilic C-F hydroxylation mechanism.