Biomimetic aryl hydroxylation derived from alkyl hydroperoxide at a nonheme iron center.: Evidence for an FeIV=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 a-arene substituents. These included the following: -C6H5 (i.e., 6-PhTPA), L-1; -o-C6H4D1 o-d(1)-L-1; -C6D5, d(5)-L-1; -m-C6H4NO2, L-2; -M-C6H4CF3, L-3; -m-C6H4Cl, L-4; -m-C6H4CH3, L-5; -m-C6H4OCH3, L-6; -p-C6H4OCH3, L-7. Additionally, the corresponding ligand with one alpha-phenyl and two a-methyl substituents (6,6-Me-2-6-PhTPA, L-8) was also synthesized. Complexes of the formulas [(L-1)Fe-II(NCCH3)(2)](ClO4)(2), [(L-n)Fe-II(OTf)(2)] (n = 1-7, OTf = -O3SCF3), and [(L-8)Fe-II(OTf)(2)](2) were obtained and characterized by H-1 NMR and UV-visible spectroscopies and by X-ray diffraction in the cases of [(L-1)Fe-II(NCCH3)(2)](ClO4)(2), [(L-6)Fe-II(OTf)(2)], and [(L-8)Fe-II(OTf)(2)](2). The complexes react with tert-butyl hydroperoxide ('BuOOH) in CH3CN solutions to give iron(III) complexes of ortho-hydroxylated ligands. The product complex derived from L-1 was identified as the solvated monomeric complex [(L1O-)Fe-III](2+) in equilibrium with its oxo-bridged climer [(L1O-)(2)Fe-III (2)(mu(2)-O)](2+), which was characterized by X-ray crystallography as the BPh4- salt. The L-8 product was also an oxo-bridged dimer, f(L8O-)(2)-Fe-II (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-II-OOR isomers in acetonitrile, whereas both [(L-1)Fe(OTf)(2)] in CH2Cl2 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, O-18 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.