Controlled nitrene transfer from a tyrosinase-like arylnitroso-copper complex

Article abstract of DOI:10.1039/c5cc02806j

The reaction between p-nitrosonitrobenzene and the tetramethylpropylenediamine-copper(i) complex yields a dinuclear complex that is structurally and electronically similar to side-on peroxo species known in Cu/O₂ chemistry. The complex reacts w

Full text of DOI:10.1039/c5cc02806j

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Controlled nitrene transfer from a tyrosinase-like
arylnitroso–copper complex†
Cite this:DOI: 10.1039/c5cc02806j
Mohammad S. Askari,a Maylis Oriobc and Xavier Ottenwaelder*a
Received 3rd April 2015,
Accepted 9th June 2015
DOI: 10.1039/c5cc02806j
www.rsc.org/chemcomm
The reaction between p-nitrosonitrobenzene and the tetramethyl-
propylenediamine–copper(I) complex yields a dinuclear complex
that is structurally and electronically similar to side-on peroxo
species known in Cu/O2 chemistry. The complex reacts with di-tert-
butylphenolate via nitrene transfer, as observed through an intermediate
and the aminophenol product obtained upon reductive work-up.
Transition metal complexes of non-innocent ligands have
attracted much attention recently due to their application in
catalysis and molecular switches.1,2 In the case of the well-
studied Cu/O2 chemistry, the extent of dioxygen reduction by
electron-rich CuI species to the superoxo (O2 ꢁ) or peroxo (O2
)
2ꢁ
ꢀ
ligand, as well as the nuclearity of the ensuing Cu/O2 complex,
are controlled by the geometric and electronic properties of the
supporting ligands (Scheme 1a).3,4 One Cu/O2 species of interest
is the m-Z2:Z2-peroxodicopper(II), P, because it is the active
oxidant in the ubiquitous enzyme tyrosinase, which promotes
oxygen-atom transfer to convert a phenol into a versatile ortho-
quinone (Scheme 1b).3–5 But for a few exceptions,6,7 the vast
majority of Cu/O2 species characterized outside a protein pocket
are typically stable only at low temperatures (ꢁ80 1C), which
makes them impractical to carry out oxygenation reactions.
Scheme 1 (a) Typical CuI/O2 reactivity with a bidentate ligand L. (b)
Tyrosinase-catalyzed oxygenation of L-tyrosine during melanogenesis.
(c) Synthesis of 1 via redox-controlled self-assembly.
to be isolated. In similar fashion, the one-electron reduction of
Arylnitroso compounds can be used as surrogates for O2 in nitrosobenzene upon binding to low-valent complexes further
reactions with CuI and the adducts are stable at room tempera- demonstrates the versatility of arylnitroso species for inner-
ture.8–10 For example, the electron-rich CuI complex with tetra- sphere electron-transfer reactions.11,12
dentate ligand Me6tren reduces nitrosobenzene by one electron
Here, we focus on the bidentate N,N,N0,N0-tetramethylpropylene-
to the radical anion, forming [(Me6tren)CuII(kO-PhNOꢀꢁ)]+ diamine (TMPD) ligand, which, in the case of Cu/O2 chemistry,
complexes. These species are structural and electronic mimics stabilizes the bis(m-oxo)dicopper(III) O isomer (Scheme 1a).13 The
of end-on CuII-superoxo species that are otherwise too transient combination of the TMPD–CuI complex and an electron-poor
arylnitroso substrate yields a P mimic that displays tyrosinase-
like reactivity (Scheme 1c).
a Department of Chemistry and Biochemistry, Concordia University, Montreal, QC,
Slow addition in THF at 25 1C of p-nitrosonitrobenzene
(ArNO) to the TMPD–Cu(I) complex, formed from a 1 : 1
TMPD–[(MeCN)4Cu](TfO) mixture,13 results in the formation
of a deep green complex, 1, which remains stable for days
under inert conditions. Clean samples of 1 are prepared via
slow addition of a [(MeCN)4Cu](TfO) solution to a solution of
TMPD and ArNO in THF at 25 1C, then precipitated with
H4B 1R6, Canada. E-mail: dr.x@concordia.ca
b
´
Laboratoire de Spectrochimie Infrarouge et Raman, Universite des Sciences et
Technologies de Lille, UMR CNRS 8516, 59655 Villeneuve d’Ascq Cedex, France
c
´
´
Institut des Sciences Moleculaires de Marseille, Aix Marseille Universite, UMR
´
7313, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
† Electronic supplementary information (ESI) available: Synthetic and computa-
tional details. CCDC 1029423 and 1029424. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c5cc02806j
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several isotope-sensitive bands (Fig. S6, ESI†). Although the
bands appear in the fingerprint region and many seem to
undergo Fermi splitting, a clear feature is observed at ca. 875
(Dn E 15) cmꢁ1, which we assign to the N–O stretch based on
computational investigation (Fig. S6 and S7, ESI†). This value is
much lower than for the delocalized double NQO bond in the
organic ArNO dimer, ArN(O)N(O)Ar (1238 (Dn = 20) cmꢁ1
,
ꢁ
Fig. S4, ESI†),15 and lower than in the mononuclear CuII(Z2-PhNOꢀ
)
species by Warren et al. (1113 (Dn = 20) cmꢁ1).9 This N–O
stretch in 1 is comparable to that of the single N–O bond
in primary hydroxylamines (910–920 cmꢁ1),20 mononuclear
Z2-PhNO2ꢁ complexes (900 cmꢁ1 range),11 and the analogous
m-Z2:Z2-PhNO2ꢁ NiII dimer (915 (Dn = 14) cmꢁ1),9 with the even
lower wavenumber in 1 likely influenced by the p-NO2 group.
The vibrational analysis of 1 thus concurs with the structural
analysis, confirming the 2-electron reduction of ArNO into a
side-on hydroxylamine dianion that mimics the side-on per-
oxide in P species.
Complex 1 is also similar to P species in terms of electronic
structure. Broken-symmetry DFT calculations indicate that 1 is
a strongly antiferromagnetically coupled CuII dimer (1798 cmꢁ1
between the ground singlet and excited triplet states), consistent
with the experimentally observed diamagnetism. The calculated
and experimental structures of 1 are within a 0.338 rms deviation
(0.175 when only considering the first coordination sphere) and
Fig. 1 ORTEP representation of the solid-state structures of the mono-
cations (a) 1 and (b) 2 at 50% ellipsoid probability (hydrogen atoms, non-
coordinated TfO-anions and crystallization solvent molecules removed for
clarity). Selected bond lengths (Å) and angles (1) for 1: N1–O1, 1.457(9);
Cu1–N1, 1.970(6); Cu1–O1, 1.926(6); Cu2–N1, 1.980(6); Cu2–O1, 1.916(6);
Cu1–O2, 2.357(6); Cu2–O3, 2.359(6); Cu1–N2, 1.983(7); Cu1–N3, 1.991(7);
Cu2–N4, 1.992(7); Cu2–N5, 2.006(8); N1–C1, 1.447(11); O1–N1–C1,
108.0(6); for 2: Cu1–N1, 1.889(3); Cu1–O1, 2.165(2); Cu1–N3, 1.989(3);
Cu1–N4, 2.018(3); O1–C12, 1.250(4); N1–C7, 1.333(4); C7–C8, 1.419(4);
C8–C9, 1.363(5); C9–C10, 1.446(4); C10–C11, 1.360(5); C11–C12,
1.460(4); C7–C12, 1.486(5); N3–Cu1–N4, 102.94(12); N1–Cu1–N3,
139.86(12); N1–Cu1–N4, 115.88(11); N1–Cu1–O1, 79.95(10).
1
pentane. H NMR spectra of 1 indicate a diamagnetic species reveals a butterfly distorted Cu2NO core (591 angle between the
with a 2 : 1 TMPD–ArNO stoichiometry. Crystallization of 1 by two CuNO planes). The two UCOs (unrestricted corresponding
slow diffusion of pentane into the reaction mixture at ꢁ30 1C orbitals) of 1 are each involving the d(x2 ꢁ y2) of one Cu atom in
afforded crystals that were suitable for X-diffraction analysis. antibonding fashion with the in-plane ps* of the ArNO moiety
The solid-state structure of 1 (as its TfOꢁ salt, Fig. 1a) is (Fig. S10, ESI†), which is reminiscent of the SOMOs of P
consistent with the solution stoichiometry and shows a dinuclear species.4,21–23 Likewise, the HOMO and LUMO of 1 are involving
species in which the NO moiety is bonded side-on to the two Cu the out-of-plane pv* and the in-plane ps* orbitals of the ArNO
centers (m-Z2:Z2), along with one of the two triflate ions bridging moiety, respectively (Fig. 2d and e), as in known P species
at axial positions. This coordination mode is reminiscent of the and the calculated peroxo analogue of 1 (Fig. S14–S16, ESI†).
well-known side-on P species (Scheme 1).3–5
As with P species in which the O2 molecule is reduced by two
electrons to form the peroxide O22ꢁ, we propose that the NQO
bond of ArNO undergoes 2-electron reduction by the CuI
precursors to a hydroxylamine dianion in 1. This proposal is
based on the significantly lengthened N–O bond in 1 at 1.457(9) Å
compared with 1.244(7)–1.253(7) Å in the organic ArNO dimer,
ArN(O)N(O)Ar,14 or other uncoordinated arylnitroso molecules
(1.131(11)–1.343(47) Å).15 This bond length matches well with
N–O single bond in Diels–Alder adducts of ArNO (N–O = 1.463(5)
and 1.4571(16) Å).16 In addition, the square-pyramidal geometry
of the Cu centers is consistent with a CuII oxidation state. The
overall Cu2NO diamond core exhibits a butterfly distortion
(381 angle between the two CuNO planes), and the CuꢂꢂꢂCu
distance (3.416 Å) is between that for butterfly-distorted P
dimers (3.2–3.4 Å)17 and P species supported by mononucleating
ligands (3.45–3.6 Å).3 Quite remarkably, 1 is one of the few
crystallographically characterized complexes exhibiting a m-Z2:Z2-
bonded C-nitroso/hydroxylamine core.9,18,19
The degree of reduction of the ArNO moiety in 1 was further
Fig. 2 (a) UV-visible spectrum of 1 (CH2Cl2, 25 1C). (b, c) TD-DFT-
probed by vibrational analysis. Thus, IR spectra of solid 1 and
calculated transitions as difference electron densities (yellow = negative,
red = positive). (d) LUMO of 1. (e) HOMO of 1.
its analogue with an Ar15NO moiety reveal the presence of
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provides novel 2-aminophenol 3 in 80% yield with respect to the
phenolate (Scheme 2, top). Noteworthy, the corresponding imino-
quinone was too reactive to be isolated, but its CuI complex 2 was
stable indefinitely in the glovebox. We assign this stability to
CuI-to-iminoquinone backbonding (Fig. S21, ESI†), which diminishes
the electrophilicity of organic fragment.
The C–H bond amination of the phenolate into 2 parallels
the reaction carried by tyrosinase and its models whereby a P
species transfers an oxygen atom to the phenolate via electro-
philic aromatic substitution to yield a dinuclear catecholate
species C (Scheme 2, bottom).5,32 In stoichiometric models of
tyrosinase, usually at ꢁ80 1C, this catecholate liberates the
catechol upon acidic quench.33–37 In one instance, C was shown
to cleave into a mononuclear CuII-semiquinone species SQ
upon careful acidification, which then liberates a mix of the
corresponding catechol and ortho-quinone.38 Complex 2 is
similar to SQ except for the different valences of Cu and the
Scheme 2 Top: 1 : 1 reaction of 1 with 2,4-di-tert-butylphenolate and
reductive work-up to 3; L = TMPD; (i) CH2Cl2, N2, 25 1C; (ii) saturated
aqueous Na2S2O4 work-up, N2. Bottom: the comparable reaction with a P
species requires careful protonation to release the SQ species; L0 = N,N0-
di-tert-butylethylenediamine; (iii) THF, ꢁ80 1C. 1 equiv. H+ per phenolate.
The UV-vis spectrum of 1 (Fig. 2), with an intense band at ring, the iminoquinone being less electron-poor than the
346 nm (e = 19.4 mMꢁ1 cmꢁ1) and several features in the visible quinone. We propose that cleavage of a dimeric C-type inter-
region, resembles closely the spectra of P species,3 particularly mediate into monomeric 2 does occur. This hypothesis is based
when a butterfly distortion is present.17 TD-DFT calculations on indirect evidence for the formation of [TMPD–CuI–OH]+
reproduce the spectrum accurately (Fig. S12, ESI†). The 346 through the products of its disproportionation: the classic
and 640 nm bands correspond to MLCT transitions involving [TMPD–CuII(m-OH)2CuIITMPD]2+ species as a precipitate and
the ps* of the nitroso moiety, consistent with the descent in Cu0 on the flask walls (while 2 is in solution). In our case,
symmetry from a C2h or C2v P to Cs in 1.17
cleavage of the C-type dimer proceeds readily at 25 1C whereas it
The electronic structure similarity between 1 and P species requires addition of an external acid in the case of Cu/O2 reactions
portends similar reactivities. Thus, reaction of 1 with 1.0 equi- at ꢁ80 1C (Scheme 2). We were unable to observe any intermediate
valent of sodium 2,4-di-tert-butylphenolate in CH2Cl2 at 25 1C between 1 and 2 at temperatures ranging from 25 to ꢁ80 1C. The
leads to the fast formation of a deep blue solution, from which insolubility of the sodium phenolate in CH2Cl2 seems to be
diamagnetic complex 2 can be isolated in 76% yield by slow important for the cleanliness of the reaction and, at the same time,
diffusion of pentane at ꢁ30 1C (Scheme 2, top). The crystal prevents accumulation of intermediates. Performing the reaction in
structure of 2 reveals a TMPD–CuI-iminoquinone complex in THF with a soluble phenolate led to intractable mixtures of
which the nitrene of p-nitroaniline (p-NO2-C6H4-N fragment) has products, highlighting the sensitivity of oxidant 1 to reaction
formally replaced a hydrogen atom ortho to the phenol. The conditions. Notwithstanding, 1 is selective for nitrogen transfer to
short C12–O1 (1.250(4) Å) and C7–N1 (1.333(4) Å) bonds and the the phenolate, and not its oxygen atom (only trace amounts of 3,5-
quinoid C–C bond distribution on the chelating aromatic ring di-tert-butyl-o-quinone were observed), a feature which will be the
are strong indicators that the new ligand is an iminoquinone, in topic of a more in-depth study of 1 and analogous species.
line with Wieghardt’s comprehensive appraisal of such ligands
Arylnitroso compounds have long been known to transiently
(C–O of 1.24, 1.30, 1.35 and C–N of 1.30, 1.35, 1.37 Å for generate nitrenes in their many unwanted side reactions lead-
iminoquinone, iminosemiquinone and aminophenolate ligands, ing to azoxy and azo compounds. Similarly, our control experi-
respectively).24–31 In addition, the trigonal-monopyramidal co- ments for the phenolate reaction with p-nitrosonitrobenzene in
ordination geometry of Cu in 2 is standard for a CuI oxidation the absence of Cu led to a intractable mixture of decomposition
state. The dihedral angle between the CuNNTMPD and CuNOiminoquinone products. The clean reactivity of 1 with the phenolate is likely
planes of 841 strongly contrasts with reported CuII-iminosemiquinone indicative of an inner-sphere mechanism similar to tyrosinase-
complexes for which minimal tetrahedral distortion (up to 261) from like oxygenations.38,39 Thus, phenolate would first bind to the
square-planarity is consistent with a CuII oxidation state.31 The Cu complex and then intramolecular nitrene transfer would
electronic assignment of 2 is further confirmed by DFT calcula- occur. This reactivity contrasts with Cu-catalyzed allylic amina-
tions conducted on both singlet (CuI-iminoquinone) and triplet tions (nitroso–ene reactions) in which C–N bond formation is
(CuII-semiquinone) forms of 2. Comparison of the optimized struc- thought to occur prior to N–O bond cleavage.40–42
tures with X-ray data shows that 2 is compatible with a singlet
We are grateful to the Natural Sciences and Engineering
CuI-iminoquinone species (Fig. S18, ESI†). Energy analysis indicates Council of Canada (NSERC) for funding.
that the singlet is stabilized by 11 kcal molꢁ1 over the triplet form
(Fig. S12, ESI†) and TD-DFT-predicted UV-vis parameters for the singlet
do match the features of the experimental spectrum (Fig. S20, ESI†).
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