Biomimetic aryl hydroxylation derived from alkyl hydroperoxide at a nonheme iron center. Evidence for an FeIV=O oxidant

Michael P. Jensen, Steven J. Lange, Mark P. Mehn, Emily L. Que, Lawrence Que

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

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 α-arene substituents. These included the following: -C6H5 (i.e., 6-PhTPA), L1; -o-C6H4D, O-d1-L1; -C6D5, d5-L1; -m-C6H4NO2, L2; -m-C6H4CF3, L3; -m-C6H4Cl, L4; -m-C6H4CH3, L5; -m-C6H4OCH3, L6; -p-C6H4OCH3, L7. Additionally, the corresponding ligand with one α-phenyl and two α-methyl substituents (6,6-Me2-6-PhTPA, L8) was also synthesized. Complexes of the formulas [(L1)FeII(NCCH3)2] (ClO4)2, [(Ln)FeII(OTf)2] (n = 1-7, OTf = -O3SCF3), and [(L8)FeII(OTf)2]2 were obtained and characterized by 1H NMR and UV-visible spectroscopies and by X-ray diffraction in the cases of [(L1)FeII(NCCH3)2] (ClO4)2, [(L6)FeII(OTf)2], and [(L8)FeII(OTf)2]2. The complexes react with tert-butyl hydroperoxide (tBuOOH) in CH3CN solutions to give iron(III) complexes of ortho-hydroxylated ligands. The product complex derived from L1 was identified as the solvated monomeric complex [(L1O-)FeIII]2+ in equilibrium with its oxo-bridged dimer [(L1O-)2FeIII22-O)]2+, which was characterized by X-ray crystallography as the BPh4- salt. The L8 product was also an oxo-bridged dimer, [(L8O-)2FeIII22-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 L1 and L8. [(L1)FeIII(OTf)2] gave rise to a mixture of high-spin (S = 5/2) and low-spin (S = 1/2) FeIII-OOR isomers in acetonitrile, whereas both [(L1)Fe(OTf)2] in CH2Cl2 and [(L8)Fe(OTf)2]2 in acetonitrile afforded only high-spin intermediates. The L1 and L8 intermediates both decomposed to form respective phenolate complexes, but their reaction times differed by 3 orders of magnitude. In the case of L1, 18O 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 α-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.

Original languageEnglish (US)
Pages (from-to)2113-2128
Number of pages16
JournalJournal of the American Chemical Society
Volume125
Issue number8
DOIs
StatePublished - Feb 26 2003

Fingerprint

Dive into the research topics of 'Biomimetic aryl hydroxylation derived from alkyl hydroperoxide at a nonheme iron center. Evidence for an Fe<sup>IV</sup>=O oxidant'. Together they form a unique fingerprint.

Cite this