Copper(I)-α-ketocarboxylate complexes: Characterization and O 2 reactions that yield copper-oxygen intermediates capable of hydroxylating arenes

Article abstract of DOI:10.1021/ja0760426

A series of copper(I)-α-ketocarboxylate complexes have been prepared and shown to exhibit variable coordination modes of the α-ketocarboxylate ligand. Reaction with O₂ induces decarboxylation of this ligand, and the derived copper-oxygen intermediate(s) has been intercepted, resulting in hydroxylation of an arene substituent on the supporting N-donor ligand. Theoretical calculations have provided intriguing mechanistic notions for the process, notably implicating hydroxylation pathways that involve novel [Cu^I-OOC(O)R] and [Cu^II-O^-? ? Cu^III=O^2-]⁺ species. Copyright

Full text of DOI:10.1021/ja0760426

Published on Web 10/25/2007
Copper(I)-r-Ketocarboxylate Complexes: Characterization and O2 Reactions
That Yield Copper-Oxygen Intermediates Capable of Hydroxylating Arenes
Sungjun Hong,† Stefan M. Huber,† Laura Gagliardi,§ Christopher C. Cramer,*,† and
William B. Tolman*,†
Department of Chemistry. Supercomputer Institute, and Center for Metals in Biocatalysis, UniVersity of Minnesota,
207 Pleasant Street SE, Minneapolis, Minnesota 55455, and Department of Physical Chemistry, Sciences II,
UniVersity of GeneVa, 30 Quai Ernest Ansermet, CH-1211 GeneVa 4, Switzerland
Received August 10, 2007; E-mail: cramer@chem.umn.edu; tolman@chem.umn.edu
Scheme 1. General Mechanism for Reactivity of
Understanding the properties of synthetic copper-oxygen in-
termediates is important for evaluating mechanisms of oxidations
FeII-R-Ketocarboxylate Sites in Enzymes and Model Complexes
by enzymes and other catalysts.1,2 A growing class of reactive
copper-oxygen complexes have been isolated or identified spec-
troscopically to date, including well-studied examples with [Cu2-
(O2)]2+, [Cu2(µ-O)2]2+, or [CuO2]+ cores.3 Mononuclear copper-
oxo species ([CuII-O-• T CuIIIdO2-]+) are less well understood.
Such species have been considered as a possible reactive intermedi-
ate in catalysis by copper enzymes (cf. peptidylglycine R-hydroxy-
lating monooxygenase,4,5 particulate methane monooxygenase6) and
in some synthetic reactions,7 but to our knowledge, they have only
been observed in the gas phase.8 Theory suggests that they should
be powerful oxidants,4,8,9 perhaps even more reactive than the related
[FeIVdO]2+ unit that has been extensively studied.10 Among the
Scheme 2. Synthesis of Copper(I) Complexes
various routes by which [FeIVdO]2+ moieties may be accessed is
that used by R-ketoglutarate-dependent non-heme iron enzymes
(Scheme 1).11 Experimental and theoretical studies12 support a
mechanism that involves reaction of O2 with a bidentate R-keto-
carboxylate complex of FeII to yield an O2 adduct (A) that attacks
the R-keto position to induce loss of CO2 and generate B. Formally
a FeII-OOC(O)R species, B, then undergoes O-O bond heterolysis
to yield the [FeIVdO]2+ moiety (C) that is generally deemed to be
responsible for attacking the C-H bond of the substrate(s).
Drawing an analogy to this chemistry, we envisioned that reaction
of O2 with a CuI-R-ketocarboxylate could similarly generate novel
[CuI-OOC(O)R] and/or derived [CuII-O-• T CuIIIdO2-]+ species.
In view of their potentially high reactivity that could make these
species difficult to observe directly, we postulated that they might
be trapped by using a supporting ligand with an arene substituent
appropriately positioned to be susceptible to intramolecular at-
tack.13,14 Herein we report the synthesis and structural characteriza-
tion of new CuI-R-ketocarboxylate complexes with such ligands,
the discovery of decarboxylation and arene hydroxylation upon
reaction of these complexes with O2, and theoretical calculations
that provide provocative mechanistic insights into the reactions.
(see below), we also prepared 5 by treating LMe with CuCl and
then AgO3SCF3. The compounds 1-5 were isolated as red-brown
(1-4) or purple (5) solids in good yields (∼75-85%) and were
fully characterized by NMR and UV-vis spectroscopy, CHN
analysis, and X-ray crystallography.15
These findings serve to illustrate a new pathway for the generation
of novel copper-oxygen intermediates relevant to oxidation
catalysis.
Using modifications of known methods,15 we prepared bidentate
LH,16 LMe, and Lm-OMe (Scheme 2), which were chosen because
they would favor low coordination numbers in their complexes,
provide a single appended arene in a position suited for intramo-
lecular oxidation,7d,13,14,17 and contain a sterically bulky 2,6-
diisopropylphenyl group to inhibit formation of bis-ligand com-
plexes (e.g., L2Cu+) and dicopper-oxygen intermediates.3 Copper(I)-
R-ketocarboxylate complexes 1-4 were synthesized by treatment
of [Cu(Mes)]4 with benzoyl or mesitoyl formic acid, followed by
addition of the N-donor ligand. For comparative O2 reactivity studies
The structures of 1 and 2 are shown in Figure 1, while those of
3-5 appear in the Supporting Information (Figures S1-S3). The
R-ketocarboxylate coordinates in chelating bidentate fashion via
the carboxylate and the ketone O atoms in 1, but in 2-4, it binds
solely through a carboxylate O atom with the keto group oriented
approximately orthogonal to the carboxylate plane (torsional angle
O1-C26-C27-O3 ) -103.5(3)°). In 5, the triflate anion binds
as a monodentate ligand to yield a three-coordinate complex. All
structures display metal-ligand bond distances typical for CuI
† University of Minnesota.
§ University of Geneva.
1
complexes. For 1-4, similar H and 13C{1H} NMR spectra are
9
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10.1021/ja0760426 CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Scheme 4. Calculated Mechanisms for O2-Induced
Decarboxylation and Arene Substituent Hydroxylation of Model 2′
Figure 1. Representations of the X-ray structures of 1 (left) and 2 (right)
as 50% thermal ellipsoids, and hydrogen atoms are omitted for clarity.
Selected interatomic distances (Å) and angles (deg) are as follows. 1: Cu1-
N1, 1.9676(19); Cu1-O1, 1.9904(19); Cu1-N2, 2.107(2); Cu1-O3,
2.1815(19); O1-C1, 1.261(3); C2-O3, 1.223(3); C2-C1, 1.545(3); O2-
C1, 1.230(3); N1-Cu1-O1, 137.52(8); N1-Cu1-N2, 79.99(8); O1-Cu1-
N2, 115.31(8); N1-Cu1-O3, 134.09(8); O1-Cu1-O3, 79.18(7); N2-
Cu1-O3, 112.07(8). 2: Cu1-O1, 1.9042(16); Cu1-N1, 1.9831(19); Cu1-
N2, 2.1113(19); Cu1-O2, 2.888(2); C26-O2, 1.216(3); C26-O1, 1.279(3);
C26-C27, 1.529(3); O3-C27, 1.216(3); O1-Cu1-N1, 154.80(8); O1-
Cu1-N2, 123.60(8); N1-Cu1-N2, 80.74(7); O2-C26-O1, 127.2(2).
Scheme 3. Reactivity of 2 and 4 with O2
for the reaction solution and [Lm-OMe-OH + X+] (X ) H or Na)
for the ligand residue were observed. Critically, when 18O2 was
used, the ESI-MS data for these species showed that one 18O atom
was incorporated into the ligand and one into the benzoate,15
consistent with expectation for a reaction pathway akin to that drawn
for Fe in Scheme 1.19
Computed mechanisms at the M06L density functional level and
including singlet-state energy corrections based on CASPT2
calculations for the reaction of model system 2′ with oxygen are
shown in Scheme 4 and, more fully, Figures S11 and S12.18
Addition of O2 delivers a complex (“O2 adduct”) that adopts either
of two energetically similar structures: a singlet structure with a
side-on bound O2 fragment, analogous in character to Cu(III)-
peroxo species supported by diketiminate ligands,3e or a triplet state
featuring end-on O2 coordination (shown). After migration of one
O atom of the O2 fragment to the ketocarbon of the ketoacid, loss
of CO2 to generate a singlet Cu(I)-peracid complex (“Peracid”) is
predicted to occur with a gas-phase free energy of activation of
15.4 kcal/mol. Decarboxylation is predicted overall to be exergonic
by about 34 kcal/mol.
Two pathways leading to oxygenation of the 2-pyridyl benzene
ring from this peracid complex were characterized. In the first, a
singlet transition-state structure involving oxidation of the ligand
by the peracid itself was located (“TS-Peracid”); this structure
features O-O and O-C bond distances of 2.47 and 2.38 Å,
respectively, and a Cu-O bond distance of 1.72 Å, so it appears
very “oxo-like” in character. In the second pathway, initial cleavage
of the peracid O-O bond led to a stable trigonal bipyramidal
copper-oxo intermediate (shown in Figure S11), which isomerizes
to a square planar isomer (“Oxo (sp)”), both of which are best
described as triplet Cu(II) oxyl species.1e,8 The square planar
intermediate is the reactive species in the hydroxylation reaction,
which proceeds through a triplet transition-state structure (“TS-
Oxo”) having Cu-O and O-C bond lengths of 1.84 and 1.93 Å,
respectively. Computationally, both paths lead to the same triplet
oxygenated cyclohexadienyl cation product, with the latter pathways
predicted to be more accessible than the former (highest activation
observed in CD2Cl2 at ambient temperature which exhibit a single
set of sharp peaks, indicating that in solution they either retain the
structures observed by X-ray diffraction or undergo fluxional
processes that are sufficiently rapid to result in an averaged spectrum
(cf. bidentate/monodentate R-ketocarboxylate isomerization).15
Density functional calculations at the M06L level18 on model
systems with unsubstituted aryl rings (hereafter 2′) found local
minima having both monodentate and bidentate coordination of the
ketoacid to copper, with the latter preferred by about 7 kcal/mol.
Exposure of solutions of 2 or 4 to O2 in acetone at -80 °C
resulted in gradual (∼2-4 h) formation of brown solutions. After
warming and removal of copper under basic conditions, a mixture
of unperturbed ligand (LH or Lm-OMe) and hydroxylated versions
(LOH or Lm-OMe-OH) was identified by 1H NMR spectroscopy
(>95% recovery, ratios indicated in Scheme 3). Acidic workup led
to the isolation (>98% recovery, NMR) of benzoyl formic acid
and benzoic acid (Scheme 3). The different extents of formation
of the hydroxylated ligand and benzoic acid for 2 versus 4 indicate
differing extents of decarboxylation and more efficient arene
hydroxylation for 4, which contains the more electron-rich arene
group that would be expected to more rapidly trap an electrophilic
copper-oxygen species. For the reaction of 4, positive ion ESI-
MS data were acquired on the crude brown reaction solution and
the recovered ligand residue. Intense peaks with correct m/z and
isotope patterns for [(Lm-OMe-O)2Cu2(benzoate)]+ and [Lm-OMe-OCu]+
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C O M M U N I C A T I O N S
Res. 2007, 40, 601-608. (f) Suzuki, M. Acc. Chem. Res. 2007, 40, 609-
617.
free energies of 10.4 and 17.8 kcal/mol relative to the peracid
intermediate, respectively).18 We note, however, that additional
kinetic constraints associated with spin crossings between the singlet
and triplet surfaces may permit either or both pathways to contribute
to the observed reactivity. Such crossings have been noted in prior
studies of Cu(II) oxyl reactivity8 and R-ketoglutarate-dependent non-
heme iron reactivity,12 and their general relevance to iron-based
oxidations has been demonstrated.10d-g Accounting for spin-crossing
barriers within the context of transition-state theory has been
discussed,20 and while a detailed kinetic analysis of this effect is
of interest, it goes beyond the scope of this communication. [We
note that we have computed the relevant spin-orbit coupling matrix
elements between the singlet and triplet states for the two TS
structures originating from the singlet peracid intermediate. They
have values of about 350 cm-1 in each case; values of this magni-
tude indicate that spin crossing should be reasonably efficient along
either of the two paths.]
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In summary, a series of copper(I)-R-ketocarboxylate complexes
have been prepared and shown to exhibit variable coordination
modes of the R-ketocarboxylate ligand. Reaction with O2 induces
decarboxylation of this ligand, and the derived copper-oxygen
intermediate(s) has(have) been intercepted, resulting in hydroxy-
lation of an arene substituent on the supporting N-donor ligand.
The results show that the oxidative decarboxylation pathway for
substrate oxidations by iron(II)-R-ketocarboxylate species in
enzymes and model complexes11,12 can be extended to copper
analogues. Theoretical calculations have yielded intriguing mecha-
nistic notions for the process, notably implicating hydroxylation
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pathways that involve novel [CuI-OOC(O)R] and [CuII-O-•
T
CuIIIdO2-]+ species. Future research will focus on identifying these
species experimentally, using them to oxidize exogenous substrates,
and differentiating between the postulated hydroxylation reaction
pathways using theoretical and experimental methods.
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(13) Examples of related arene substituent hydroxylations using mononuclear
complexes have been reported. For cases proposed to involve a [CuO]+
intermediate, see refs 7c and d, and for examples involving other types
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Matsumoto, T.; Suzuki, M.; Cramer, C. J.; Itoh, S. J. Am. Chem. Soc.
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S. J.; Mehn, M. P.; Que, E. L.; Que, L., Jr. J. Am. Chem. Soc. 2003, 125,
2113-2128.
Acknowledgment. We thank the National Institutes of Health
(GM47365 to W.B.T.), the National Science Foundation (CHE06-
10183 to C.J.C.), the Swiss National Science Foundation (200021-
111645/1 to L.G.), and the DAAD (fellowship to S.M.H.) for
financial support of this research.
(14) For
a copper(II)-promoted ortho-hydroxylation of 2-phenylpyridine
Supporting Information Available: Full details of experimental
and calculation procedures, characterization data, spectra, X-ray
structure drawings of 3-5, calculated reaction mechanism and coor-
dinates (PDF), and X-ray crystallographic information (CIFs). This
material is available free of charge via the Internet at http://pubs.acs.org.
proposed to involve a single electron transfer mechanism, see: Chen, X.;
Hao, X. S.; Goodhue, C. E.; Yu, J. Q. J. Am. Chem. Soc. 2006, 128,
6790-6791.
(15) For details, see Supporting Information.
(16) (a) Bianchini, C.; Mantovani, G.; Meli, A.; Migliacci, F.; Laschi, F.
Organometallics 2003, 22, 2545-2547. (b) Bianchini, C.; Lenoble, G.;
Oberhauser, W.; Parisel, S.; Zanobini, F. Eur. J. Inorg. Chem. 2005, 4794-
4800.
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