Aryl hydroxylation from a mononuclear copper-hydroperoxo species

Article abstract of DOI:10.1021/ja071704c

Mononuclear Cu^II-^-OOH entities or derived species have been seriously considered as important in chemical or biochemical oxidations. Yet, synthetic chemistry investigations have thus far revealed they have very limited substrate reactivity. Here, a significant aryl hydroxylation reaction occurs from a hydroperoxocopper(II) complex possessing a tripodal tetradentate ligand with appended aryl substituent. A phenolate-Cu(II) complex is detected following a proposed O-O cleavage event, that is suggested on the basis of precedent from non-heme iron chemistry. A bis-μ-oxo-dicopper(III) complex as active oxygenating agent is ruled out. Copyright

Full text of DOI:10.1021/ja071704c

Published on Web 05/11/2007
Aryl Hydroxylation from a Mononuclear Copper-Hydroperoxo Species
Debabrata Maiti, Heather R. Lucas, Amy A. Narducci Sarjeant, and Kenneth D. Karlin*
Department of Chemistry, The Johns Hopkins UniVersity, Baltimore, Maryland 21218
Received March 11, 2007; E-mail: karlin@jhu.edu
Research advances concerning the active-site chemistry of
dioxygen activating copper enzymes have shown that single copper
center O2-derived reactive Cu-oxygen species are implicated in a
number of situations. This includes biological oxygenases such as
peptidylglycine-R-hydroxylating monooxygenase (PHM) and dopam-
ine-â monoxygenases (DâM).1 While these possess two copper ions
per active subunit which are ∼11 Å apart,2a the CuM (≡CuB) site
is where substrate H-atom abstractions occur, resulting in overall
O2/ascorbate copper-mediated hydroxylation chemistry.1a,b Also,
single-copper ion mediated amino-acid oxygenation or oxidative-
coupling occurs in the biogenesis of active-site cofactors in 2,4,5-
trihydroxyphenylalanine (TOPA) formation (copper amine oxidases)
and Tyr-Cys coupling (galactose oxidase).1c,2b,c
In the last few decades, coordination chemistry efforts have
generated considerable insights into ligand-CuI/O2 chemistry, such
Figure 1. X-ray structure of 1, as precursor to hydroperoxo-CuII complex
as the generation of new types of copper-dioxygen adducts, their
kinetics of formation, structures, associated spectroscopy, and
reactivity.3 Yet, the chemistry of mononuclear entities such as
cupric-superoxides (CuII-O2•-) and hydroperoxides (CuII--OOH)
is not as well developed.1a For a long time, a CuII--OOH species
was considered to be the likely key intermediate in DâM and PHM
reactivity, while more recent experimental and computational
advances suggest an active-site CuII-O2•- entity most likely effects
initial substrate H•-abstraction.1b,4 However, other computational
studies suggest that the O2-derived O-O bond first cleaves to give
a cupryl (e.g., CuIIIdO T CuII-O•)5 or higher oxidation state (e.g.,
2, leading to a phenolate-CuII entity which upon demetalation gives the
o-hydroxylated phenol 6tBPOH. The oxygen atom(s) red-labeling tracks
results from 18-O substitutions, see text.
spectrum for 2 is consistent with mononuclear formulation, g|)
2.245, g ) 2.042, A| ) 180 G.13 Direct evidence comes from
ESI-MS (-80 °C, acetone), showing a strong parent peak cluster
with m/z 518.01 (and possessing the expected 63,65Cu pattern)
corresponding to [(6tbp)CuII(-OOH)]+. When formation of 1 was
instead carried out using H218O2, the positive ion peak shifts to
522.04, attributed to [(6tbp)CuII(-18O18OH)]+; fitting of the parent
peak pattern around m/z ) 522 indicated >99% 18-O incorpora-
tion.13
[CuO]2+ 6a species and this effects the H-atom abstraction.6
)
Synthetic chemistry investigations have thus far revealed only
limited substrate reactivity with mononuclear CuII-O2•- 7 or CuII--
OOH complexes,8,9 especially with C-H containing substrates.
There are as yet no discrete examples or evidence for mononuclear
high-valent copper-oxo species.1a,10
While [(6tbp)CuII(-OOH)]+ (2) is quite stable in solution at -80
°C, warming results in a change in color to brownish-green. TLC
and ESI-MS data obtained from the product solution which was
stripped of copper ion by addition of Na2EDTA (aq) and extracted
into CH2Cl2 revealed unreacted 6tBP ligand. However, a new
product obtained in ∼20% yield (which decreases with less added
H2O2) after chromatography exhibits m/z ) 439.47, corresponding
to a hydroxylated 6tBP moiety, [6tBPOH + H]+ and m/z ) 461.47
[6tBPOH + Na] (Figure 1). A parent anion peak at m/z ) 437.20
(6tBPO-) was obtained when mass spectra were recorded in
negative ion mode.13 This product is the o-phenol (Figure 1), as
Two groups have recently achieved substrate C-H activation
chemistries starting from well-characterized dinuclear µ--OOH-
dicopper(II) complexes, oxidative N-dealkylation or RCH2CtN
oxidative cleavage (to RCHdO + cyanide).11 Suzuki has also
observed a hydrocarbon attack from a CuII (-OH)2 + H2O2 reaction,
2
giving a CuII--OORligand-substrate product.12 Here, we rather present
the chemistry of a mononuclear CuII--OOH complex which leads
to the hydroxylation of an aryl substrate.
1
deduced by H NMR and 13C NMR data analyses. The 6tBPOH
O-atom is derived from the CuII--OOH moiety; an ion shift from
461.47 (6tBPOH + Na) to 463.63 (6tBP18OH + Na) was recorded
for the 6tBP18OH when H218O2 was used to generate 2.13
Complex 1, with 6tBP ligand, is a derivative of the well-studied
tris(2-pyridylmethyl)amine (TMPA) ligand, however it possesses
a proximate aryl group (Figure 1).13 The X-ray structure13 of the
CuII complex as perchlorate salt, [(6tbp)CuII(acetone)]2+ (1) (Figure
1), reveals a square-based pyramidal coordination sphere with labile
acetone ligand in an equatorial position; a longer axial ligand is
provided by the pyridyl group with the 6-aryl substituent, Cu-N4
) 2.4454(13) Å. In the manner commonly used to generate
hydroperoxo-CuII complexes,8 we added ∼5 equiv H2O2/Et3N using
50% H2O2(aq) to a blue acetone solution of 1 at -80 °C. The green
product solution is formulated as the hydroperoxide [(6tbp)CuII-
(-OOH)]+ (2); λmax ) 380 nm (ꢀ ) 1500 M-1 cm-1), assignable
to a -OOH f CuII LMCT band.14 A typical CuII axial EPR
Most interestingly, when the warmed reaction solution is
subjected to ESI-MS analysis (prior to EDTA treatment), the
predominant higher molecular weight species detected occurs at
m/z ) 500.52, corresponding to a likely reaction intermediate, a
phenolate-CuII complex [(6tbpO-)CuII]+ (Figure 1), confirmed again
by the shift to m/z ) 502.49 ([(6tbp18O-)CuII]+) when H218O2 is
introduced to the reaction; a characteristic ArO--to-Cu(II) charge
transfer absorption is also detected.13,15 Taken together, the data
suggest that hydroperoxo-CuII (2) derived chemistry effects the aryl
hydroxylation of 6tBP, a reaction that up to this point has only
9
6998
J. AM. CHEM. SOC. 2007, 129, 6998-6999
10.1021/ja071704c CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
important entities for further detailed mechanistic investigations
which could lead to insights into copper promoted O-O cleavage
and new high-valent copper-oxo chemistry of chemical and
biochemical consequence.
Acknowledgment. This work was supported by a grant from
the National Institutes of Health (K.D.K., Grant GM28962).
Supporting Information Available: Synthetic details, descriptions
of reactions, product analyses/characterization, and CIF files. This
material is available free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Itoh, S. Curr. Opin. Chem. Biol. 2006, 10, 115-122. (b) Klinman, J.
P. J. Biol. Chem. 2006, 281, 3013-3016. (c) McGuirl, M. A.; Dooley,
D. M. Copper Proteins with Type 2 Sites. In Encyclopedia of Inorganic
Chemistry, 2nd ed; King, R. B., Ed.; John Wiley & Sons Ltd.: Chichester,
2005; Vol. II, pp 1201-1225.
(2) (a) Prigge, S. T.; Eipper, B.; Mains, R.; Amzel, L. M. Science 2004, 304,
864-867. (b) Okeley, N. M.; Van der Donk, W. A. Chem. Biol. 2000, 7,
R159-R171. (c) Whittaker, M. M.; Whittaker, J. W. J. Biol. Chem. 2003,
278, 22090-22101.
(3) (a) Mirica, L. M.; Ottenwaelder, X.; Stack, T. D. P. Chem. ReV. 2004,
104, 1013-1045. (b) Lewis, E. A.; Tolman, W. B. Chem. ReV. 2004,
104, 1047-1076. (c) Quant Hatcher, L.; Karlin, K. D. J. Biol. Inorg. Chem.
2004, 9, 669-683.
(4) Chen, P.; Solomon, E. I. J. Am Chem. Soc. 2004, 126, 4991-5000.
(5) Decker, A.; Solomon, E. I. Curr. Opin. Chem. Biol. 2005, 9, 152-163.
(6) (a) Crespo, A.; Marti, M. A.; Roitberg, A. E.; Amzel, L. M.; Estrin, D.
A. J. Am. Chem. Soc. 2006, 128, 12817-12828. (b) Yoshizawa, K.;
Kihara, N.; Kamachi, T.; Shiota, Y. Inorg. Chem. 2006, 45, 3034-3041.
(7) Maiti, D.; Fry, H. C.; Woertink, J. S.; Vance, M. A.; Solomon, E. I.;
Karlin, K. D. J. Am. Chem. Soc. 2007, 129, 264-265.
(8) Fujii, T.; Naito, A.; Yamaguchi, S.; Wada, A.; Funahashi, Y.; Jitsukawa,
K.; Nagatomo, S.; Kitagawa, T.; Masuda, H. Chem. Commun. 2003,
2700-2701.
been attributed to dinuclear complexes, either η2:η2-peroxodicopper-
(II) or bis-µ-oxo dicopper(III) species.3b,16 We suggest a mechanism
where the CuII--OOH moiety undergoes O-O cleavage, leading
to a high-valent copper-oxo species which attacks the aryl
group.17-20 This suggestion is compelling since for an iron complex
with a nearly identical 6-PhTPA ligand {6-PhTPA is like 6tBP but
with a 6-phenyl rather than 6-(4-tBuphenyl) group on one pyridyl
arm}, Que and co-workers21 established homolytic cleavage from
an FeIII--OOR species to give an FeIVdO moiety which effects
ligand aryl hydroxylation.22
To investigate the possibility that a dioxygen derived species
may rather be effecting this aryl hydroxylation, we examined the
product(s) of O2 reaction with a copper(I) complex of 6tBP, [(6tbp)-
CuI]+ (3, X-ray, Scheme 1). Bubbling O2 directly through a -80
°C THF solution of 3 results in a color change from light to bright
brownish-yellow, giving an EPR silent bis-µ-oxo-dicopper(III)
complex [{(6tbp)CuIII}2(O)2]2+ (4), λmax ) 383 nm (ꢀ ) 7000 M-1
cm-1) (Scheme 1). The formulation is based on well-established
spectral signatures3a and the result is identical to that recently
reported for a [(6-PhTPA)CuI]+/O2 reaction [6-PhTPA described
(9) Yamaguchi, S.; Masuda, H. Sci. Technol. AdV. Mat. 2005, 6, 34-47.
(10) Dinuclear copper-oxo species, CuIII2(O2-)2 complexes, are well known.3
(11) (a) Itoh, K.; Hayashi, H.; Furutachi, H.; Matsumoto, T.; Nagatomo, S.;
Tosha, T.; Terada, S.; Fujinami, S.; Suzuki, M.; Kitagawa, T. J. Am. Chem.
Soc. 2005, 127, 5212-5223. (b) Li, L.; Sarjeant, A. A. N.; Vance, M. A.;
Zakharov, L. N.; Rheingold, A. L.; Solomon, E. I.; Karlin, K. D. J. Am.
Chem. Soc. 2005, 127, 15360-15361.
above], giving [{(6-PhTPA)CuIII}2(O)2]2+ (5), νCu-O ) 599 cm-1 23
.
(12) Mizuno, M.; Honda, K.; Cho, J.; Furutachi, H.; Tosha, T.; Matsumoto,
T.; Fujinami, S.; Kitagawa, T.; Suzuki, M. Angew. Chem., Int. Ed. 2006,
45, 6911-6914.
Complex 4 in THF is unstable even at -80 °C, decomposing within
15 min and affording oxidized solvent, 2-hydroxy-THF (∼40%)
and γ-butyrolactone (<5%).13 When the formation of 4 was carried
out in toluene at -80 °C, thermal decomposition produces PhCHO
(35%) with 70% 18-O incorporation (giving PhCH18O) when using
18O2 labeled 4. The reaction of 4 with 2,4-di-tert-butylphenol in
diethyl ether produces the typical oxidative coupling product
4,4′,6,6′-tetra-t-butyl-2,2′-biphenol (50%) after low-temperature
reaction, warming, and workup (Scheme 1).
The reactivity of [{(6tbp)CuIII}2(O)2]2+ (4) with substrates
parallels the behavior known for [CuIII2(O)2]2+ species.3 Warming
[{(6-PhTPA)CuIII}2(O)2]2+ (5) gives a trace of oxidatively N-
dealkylated ligand decomposition products.23 Thus, it appears that
neither 4 nor 5 effect aryl hydroxylation chemistry, which does
howeVer deriVe from the CuII--OOH complex [(6tbp)CuII(-OOH)]+
(2). The lack of aryl ring hydroxylation of 6tBP or 6-PhTPA by
the [CuIII2(O)2]2+diamond core may be attributed to axial positioning
of the arylpyridyl arm, precluding a geometry favorable for oxo-
atom attack and transfer to the pendant aryl group.23 Axial ligand
elongation is observed for 6-substituted 2-pyridyl ligand arms in
[{(6-Me2TPA)CuIII}2(O)2]2+ (5) (X-ray).24,25 However, the proximity
of a reactive species and aryl substrate in the 6-position of a
coordinating pyridyl ligand does lead to aryl hydroxylation for [(6-
PhTPA)FeIII(-OOR)]2+, as mentioned above, in our complex
[(6tbp)CuII(-OOH)]+ (2) and for a CuIII2(O2-)2 species supported
by the bidentate 2-(diethylaminomethyl)-6-phenylpyridine ligand.26
In summary, the chemistry presented reveals that a significant
aryl hydroxylation chemistry can be effected by a discrete mono-
nuclear CuII-hydroperoxo complex or derived species. The reaction
does not proceed from bis-µ-oxo-dicopper(III) chemistry. [(6tbp)CuII-
(-OOH)]+ (2) or complexes of similar design may now serve as
(13) See Supporting Information.
(14) Yamaguchi, S.; Kumagai, A.; Nagatomo, S.; Kitagawa, T.; Funahashi,
Y.; Ozawa, T.; Jitsukawa, K.; Masuda, H. Bull. Chem. Soc. Jpn. 2005,
78, 116-124.
(15) In fact, UV-vis & EPR spectroscopy, along with ESI-MS interrogation
indicates low-temperature formation of solutions with Cu(II) plus a
phenoxyl radical (thus oxygenation has already occurred) when reaction
solutions are left at -44 °C.13 No evidence was obtained which could
relate to the identification of any new species, for example, a cupryl
species.
(16) Mirica, L. M.; Vance, M.; Rudd, D. J.; Hedman, B.; Hodgson, K. O.;
Solomon, E. I.; Stack, T. D. P. Science 2005, 308, 1890-1892.
(17) We note that in similarly constructed CuII--OOH complexes with
modified TMPA frameworks, Masuda14,18 has shown that a 6-N-H group
on pyridyl-ligand arms hydrogen-bonds to the proximal oxygen atom of
a CuII-hydroperoxo group. Thus, the ortho C-H substrate of the 6-aryl
moiety of 6tBP may certainly be in close proximity to either a hydroperoxo
O-atom of [(6tbp)CuII(-OOH)]+ (2) or oxo atom of a high-valent Cu-O
intermediate.
(18) Wada, A.; Harata, M.; Hasegawa, K.; Jitsukawa, K.; Masuda, H.; Mukai,
M.; Kitagawa, T.; Einaga, H. Angew. Chem., Int. Ed. 1998, 37, 798-
799.
(19) Perhaps the reaction occurs by concerted attack of the -OOH in 2 on the
aryl substrate. Otherwise, Yu and coworkers20 recently describe the Cu-
(II)-promoted aryl hydroxylation of a 2-phenylpyridyl moiety, suggesting
the reaction proceeds via electron-transfer giving an aryl cation-radical,
nucleophilic ring attack, etc.
(20) Chen, X.; Hao, X. S.; Goodhue, C. E.; Yu, J. Q. J. Am. Chem. Soc. 2006,
128, 6790-6791.
(21) Jensen, M. P.; Lange, S. J.; Mehn, M. P.; Que, E. L.; Que, L. J. Am
Chem. Soc. 2003, 125, 2113-2128.
(22) Seo, M. S.; Kamachi, T.; Kouno, T.; Murata, K.; Park, M. J. P.; Yoshizawa,
K.; Nam, W. Angew. Chem., Int. Ed. 2007, 46, 2291-2294.
(23) Jensen, M. P.; Que, E. L.; Shan, X. P.; Rybak-Akimova, E.; Que, L. Dalton
Trans. 2006, 3523-3527.
(24) 6-Me2TPA ) (2-pyridylmethyl)bis(6-methyl-2-pyridylmethyl)amine.
(25) Hayashi, H.; Fujinami, S.; Nagatomo, S.; Ogo, S.; Suzuki, M.; Uehara,
A.; Watanabe, Y.; Kitagawa, T. J. Am. Chem. Soc. 2000, 122, 2124-
2125.
(26) Holland, P. L.; Rodgers, K. R.; Tolman, W. B. Angew. Chem., Int. Ed.
1999, 38, 1139-1142.
JA071704C
9
J. AM. CHEM. SOC. VOL. 129, NO. 22, 2007 6999