Regioselective hydroxylation of the xylyl linker in a diiron(III) complex having a carboxylate-rich ligand with H 2 O 2 † Hideki Furutachi, a Mizue Murayama, a Amane Shiohara, a Satoshi Yamazaki, a Shuhei Fujinami, a Akira Uehara, a Masatatsu Suzuki,* a Seiji Ogo, b Yoshihito Watanabe c and Yonezo Maeda d a Department of Chemistry, Faculty of Science, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. E-mail: suzuki@cacheibm.s.kanazawa-u.ac.jp b Department of Material and Life Science, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan c Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan d Department of Chemistry, Faculty of Science, Kyushu University, Hakozaki, Higasi-ku, Fukuoka 812-0053, Japan Received (in Cambridge, UK) 15th April 2003, Accepted 10th June 2003 First published as an Advance Article on the web 25th June 2003 Reaction of a diiron(III) complex having a xylta 42 ligand (N,N,NA,NA-m-xylylenediamine tetraacetate) with H 2 O 2 re- sulted in regioselective hydroxylation of the m-xylyl linker. The reaction mimics the self-hydroxylation of a phenyl- alanine side chain found for ribonucleotide reductase (R2- W48F/D84E). Hydroxylation of alkanes and arenes catalyzed by iron com- plexes is of current interest for understanding the dioxygen activation mechanisms of non-heme diiron proteins such as methane monooxygenase, ribonucleotide reductase, and fatty acid desaturase. 1,2 Recently, self-hydroxylation of a phenyl- alanine side chain, which is located in close proximity to the diiron center, has been reported for ribonucleotide reductase (R2-W48F/D84E). 3 Many model compounds have been devel- oped and their reactivity toward various substrates has been investigated. 2,4 Even though excellent systems for hydroxyla- tion of arenes have been developed for the copper complexes, 2,5 only a limited number of examples for efficient hydroxylation of arene groups by iron complexes have been known. 6 The hydroxylation of a phenyl group in the ligand was reported for some diiron complexes having a carboxylate-rich coordination environment such as edtp in their reactions with either H 2 O 2 or O 2 . 6a It was also found that the reaction of a mononuclear iron(II) complex of 6Ph-tpa (N 4 -donor set) with t BuOOH hydroxylates a phenyl pendant of the supporting ligand. 6b Since the diiron centers of the above enzymes share carboxylate-rich coordination environment, it is of particular interest to in- vestigate the oxidation reactions of diiron complexes having carboxylate-rich ligands. Herein, we report a regioselective hydroxylation of a xylyl linker by the reaction of a diiron(III) complex bearing carboxylate-rich coordination environment (N,N,NA,NA-m-xylylenediamine tetraacetate: xylta 42 ) with H 2 O 2 , where two iron(III) ions are linked by a xylyl group. The reaction mimics the self-hydroxylation of a phenylalanine side chain found for R2-W48F/D84E. 3 To an aqueous suspension containing 1 equiv. of H 4 xylta, 4 equiv. of Et 3 N, and 2 equiv. of FeCl 3 was added 6 equiv. of sodium acetate to generate a dark yellowish green solution (Scheme 1). The negative ion ESI-TOF/MS spectrum of the solution diluted by acetonitrile (1 : 1) in the range of m/z = 20 to 1000 showed a signal at m/z (%): 550.9614 (100) with a characteristic distribution of isotopomers attributable to a diiron(III) species {[Fe 2 (xylta)(O)(CH 3 CO 2 )]} 2 (accurate mass : m/z = 550.9688) (Fig. S1).† All attempts to crystallize this species were in vain so far. Addition of 5 equiv. of H 2 O 2 to the solution at 0 °C resulted in a rapid color change to red. The electronic spectral change showed that the reaction quickly proceeds within several seconds at 0 °C and no detectable intermediate was observed at present stage (Fig. S2).† 7 The ESI-TOF/MS spectrum of the solution diluted by acetonitrile (1 : 1) showed two signals at m/z (%): 608.9652 (100) and 506.9423 (29) attributable to the hydroxylated species having a (m-phenoxo)diiron(III) core {[Fe 2 (xylta-O)(CH 3 CO 2 ) 2 ]} 2 (1, accurate mass : m/z = 608.9743) and a {[Fe 2 (xylta-O)(O)]} 2 (accurate mass : m/z = 506.9426), respectively, together with a signal of {[Fe 2 (xylta)(O)(CH 3 CO 2 )]} 2 (I = 27%) (Fig. S1).† Addition of a methanol solution of (n-Bu) 4 NBr into the red aqueous solution afforded red crystals (n-Bu) 4 N[Fe 2 (xylta- O)(CH 3 CO 2 ) 2 ]·3H 2 O (1·Bu 4 N) (yield = 62%) suitable for X- ray crystallography (Fig. 1).‡ The crystal structure of 1 clearly shows that the xylyl linker of xylta 42 is hydroxylated and the resulting phenolate oxygen bridges the two iron atoms. Each iron atom has a distorted octahedral geometry with the N 1 O 5 donor set and is triply bridged by the phenolate oxygen and two acetate groups providing a bis(m-acetato)(m-phenoxo)diiron(III) core as found for a closely related complex Me 4 N[Fe 2 (5Me- HXTA)(CH 3 CO 2 ) 2 ]. 8 Isotope labeling experiments using H 2 18 O 2 (in H 2 16 O) showed that the phenolate oxygen of 1 comes from the hydrogen peroxide ({[Fe 2 (xylta- 18 O)(CH 3 CO 2 ) 2 ]} 2 (m/z (%): 610.9687 (100)) (Fig. S3).† The yield and regioselectivity for hydroxylation of the xylyl linker were assessed by the 1 H NMR spectrum after the reaction mixture was treated by sodium dithionite and potassium cyanide. The 1 H NMR spectrum of the reaction mixture clearly showed only two sets of signals arising from xylta 42 and the oxidized ligand (xylta-O 52 ), and there was no signal due to other modified ligand (Fig. S4).† About 74 (±2)% of xylta 42 was converted into xylta-O 52 (H 2 O 2 = 5 equiv./[Fe 2 ]). Thus, the reaction demonstrates the regioselective hydroxylation of the xylyl linker as observed for the reaction of [Cu 2 (XYL–H)] 2+ with dioxygen. 5a The oxygenation yield of xyta-O 52 was almost the same even when excess H 2 O 2 was used. Unlike the diiron complexes reported by Fontecave et al., 6a no hydroxylation occurred when H 2 O 2 was replaced with dioxygen in the presence of ascorbic acid as a reductant. Replacement of the carboxylate groups in xylta 42 by pyridyl groups (pyxyl) afforded a very different tetranuclear iron(III) † Electronic supplementary information (ESI) available: experimental details, ESI-mass, UV–vis, and 1 H NMR spectra. See http://www.rsc.org/ suppdata/cc/b3/b304171a/ Scheme 1 Reaction scheme for iron(III) complexes with H 2 O 2 . This journal is © The Royal Society of Chemistry 2003 1900 CHEM. COMMUN. , 2003, 1900–1901 DOI: 10.1039/b304171a