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Jensen MP, Lange SJ, Mehn MP, Que EL, Que L Jr: Biomimetic aryl hydroxylation derived from alkyl hydroperoxide at a nonheme iron center. J Am Chem Soc. 2003 Feb 26;125(8):2113-28.
Evidence for an Fe (IV)=O oxidant.. Many nonheme iron-dependent enzymes activate dioxygen to catalyze hydroxylations of arene substrates. Key features of this chemistry have been developed from complexes of a family of tetradentate tripodal ligands obtained by modification of tris (2-pyridylmethyl) amine (TPA) with single alpha-arene substituents. These included the following: -C (6) H (5) (i.e., 6-PhTPA), L (1); -o-C (6) H (4) D, o-d (1)-L (1); -C (6) D (5), d (5)-L (1); -m-C (6) H (4) NO (2), L (2); -m-C (6) H (4) CF (3), L (3); -m-C (6) H (4) Cl, L (4); -m-C (6) H (4) CH (3), L (5); -m-C (6) H (4) OCH (3), L (6); -p-C (6) H (4) OCH (3), L (7). Additionally, the corresponding ligand with one alpha-phenyl and two alpha-methyl substituents (6,6-Me (2)-6-PhTPA, L (8)) was also synthesized. Complexes of the formulas [(L (1)) Fe (II)(NCCH (3))(2)](ClO (4))(2), [(L (n)()) Fe (II)(OTf)(2)] (n = 1-7, OTf = (-) O (3) SCF (3)), and [(L (8)) Fe (II)(OTf)(2)](2) were obtained and characterized by (1) H NMR and UV-visible spectroscopies and by X-ray diffraction in the cases of [(L (1)) Fe (II)(NCCH (3))(2)](ClO (4))(2), [(L (6)) Fe (II)(OTf)(2)], and [(L (8)) Fe (II)(OTf)(2)](2). The complexes react with tert-butyl hydroperoxide ((t)() BuOOH) in CH (3) CN solutions to give iron (III) complexes of ortho-hydroxylated ligands. The product complex derived from L (1) was identified as the solvated monomeric complex [(L (1) O (-)) Fe (III)](2+) in equilibrium with its oxo-bridged dimer [(L (1) O (-))(2) Fe (III)(2)(mu (2)-O)](2+), which was characterized by X-ray crystallography as the BPh (4)(-) salt. The L (8) product was also an oxo-bridged dimer, [(L (8) O (-))(2) Fe (III)(2)(mu (2)-O)](2+). Transient intermediates were observed at low temperature by UV-visible spectroscopy, and these were characterized as iron (III) alkylperoxo complexes by resonance Raman and EPR spectroscopies for L (1) and L (8). [(L (1)) Fe (II)(OTf)(2)] gave rise to a mixture of high-spin (S = 5/2) and low-spin (S = 1/2) Fe (III)-OOR isomers in acetonitrile, whereas both [(L (1)) Fe (OTf)(2)] in CH (2) Cl (2) and [(L (8)) Fe (OTf)(2)](2) in acetonitrile afforded only high-spin intermediates. The L (1) and L (8) intermediates both decomposed to form respective phenolate complexes, but their reaction times differed by 3 orders of magnitude. In the case of L (1), (18) O isotope labeling indicated that the phenolate oxygen is derived from the terminal peroxide oxygen via a species that can undergo partial exchange with exogenous water. The iron (III) alkylperoxo intermediate is proposed to undergo homolytic O-O bond cleavage to yield an oxoiron (IV) species as an unobserved reactive intermediate in the hydroxylation of the pendant alpha-aryl substituents. The putative homolytic chemistry was confirmed by using 2-methyl-1-phenyl-2-propyl hydroperoxide (MPPH) as a probe, and the products obtained in the presence and in the absence of air were consistent with formation of alkoxy radical (RO (*)). Moreover, when one ortho position was labeled with deuterium, no selectivity was observed between hydroxylation of the deuterated and normal isotopomeric ortho sites, but a significant 1,2-deuterium shift ("NIH shift") occurred. These results provide strong mechanistic evidence for a metal-centered electrophilic oxidant, presumably an oxoiron (IV) complex, in these arene hydroxylations and support participation of such a species in the mechanisms of the nonheme iron- and pterin-dependent aryl amino acid hydroxylases. |
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