Copper-Carbene Intermediates in the Copper-Catalyzed Functionalization of O-H Bonds

Article abstract of DOI:10.1002/chem.201500776

Copper-carbene [Tp^xCu=C(Ph)(CO₂Et)] and copper-diazo adducts [Tp^xCu{η¹-N₂C(Ph)(CO₂Et)}] have been detected and characterized in the context of the catalytic functionalization of O-H bonds through carbene insertion by using N₂=C(Ph)(CO₂Et) as the carbene source. These are the first examples of these type of complexes in which the copper center bears a tridentate ligand and displays a tetrahedral geometry. The relevance of these complexes in the catalytic cycle has been assessed by NMR spectroscopy, and kinetic studies have demonstrated that the N-bound diazo adduct is a dormant species and is not en route to the formation of the copper-carbene intermediate.

Full text of DOI:10.1002/chem.201500776

DOI: 10.1002/chem.201500776
Full Paper
&
Carbenes
Copper–Carbene Intermediates in the Copper-Catalyzed
Functionalization of OÀH Bonds
Ana Pereira,[a] Yohan Champouret,[b, c] Carmen Martín,[a] Eleuterio lvarez,[d]
Michel Etienne,*[b, c] Tomµs R. Belderraín,*[a] and Pedro J. PØrez*[a]
Abstract: Copper–carbene [TpxCu=C(Ph)(CO2Et)] and
copper–diazo adducts [TpxCu{h1-N2C(Ph)(CO2Et)}] have been
detected and characterized in the context of the catalytic
functionalization of OÀH bonds through carbene insertion
by using N2=C(Ph)(CO2Et) as the carbene source. These are
the first examples of these type of complexes in which the
copper center bears a tridentate ligand and displays a tetra-
hedral geometry. The relevance of these complexes in the
catalytic cycle has been assessed by NMR spectroscopy, and
kinetic studies have demonstrated that the N-bound diazo
adduct is a dormant species and is not en route to the for-
mation of the copper–carbene intermediate.
Introduction
Metal-catalyzed transfer reactions of carbene from diazo com-
pounds, N2CR1R2, to unsaturated as well as saturated substrates
constitute a powerful tool for the formation of new carbon–
carbon or carbon–heteroatom bonds.[1] The particular case of
a EÀH bond (E=C, N, O) provides the formation of a CÀE
bond (Scheme 1), a moiety that is present in a plethora of nat-
ural and synthetic molecules. However, the insertion of a car-
bene group into such EÀH bond seems to be underexploited
in spite of its potential.[2] For example, inert CÀH bonds of
poorly reactive molecules such as alkanes,[3] including meth-
ane,[4] have been functionalized by this methodology. More re-
active NÀH[5] or OÀH[6] bonds have also been converted into
Scheme 1. General metal-catalyzed EÀH functionalization by the carbene in-
sertion methodology.
the corresponding derivatives. The asymmetric versions of
those reactions with X=C,[7] N,[8] O[9] have also been reported.
Several metals promote this transformation: rhodium,
copper, iron, or ruthenium are the most frequently employed,
copper being the preferred one.[2] The mechanism proposed
for this transformation is shown in Scheme 2. Usually, the initial
copper complex dissociates a ligand to generate a coordinative-
ly and electronically unsaturated species that reacts with the
diazo compound. There are several coordination modes for
a diazo compound N2CR1R2 with the copper center, although it
has been proposed that only the complex bound through the
diazo-carbon atom (A) is productive for the formation of the
copper–carbene intermediate (MC). Direct observations of
such species (MC), always in the context of olefin cyclopropa-
nation reactions, are rare (Scheme 2).[10] In a subsequent and
final step, the EÀH bond interacts with the copper–carbene
(MC) to afford the insertion product. The general catalytic
cycle shown in Scheme 2 has been built[2] on the basis of evi-
dences obtained from different systems, some of them being
irrelevant to the EÀH insertion reaction. With the aim of pro-
viding evidences of the different steps within the same catalyt-
ic cycle, we report herein a complete study on the reaction of
[a] A. Pereira, Dr. C. Martín, Prof. Dr. T. R. Belderraín, Prof. Dr. P. J. PØrez
Laboratorio de Catµlisis HomogØnea
Unidad Asociada al CSIC
CIQSO- Centro de Investigación en Química Sostenible
and Departamento de Química y Ciencia de Materiales
Universidad de Huelva, 21007 Huelva (Spain)
Fax: (+34)959219942
E-mail: trodri@dqcm.uhu.es
perez@dqcm.uhu.es
[b] Dr. Y. Champouret, Prof. Dr. M. Etienne
CNRS; LCC (Laboratoire de Chimie de Coordination)
205, route de Narbonne, BP 44099
31077 Toulouse Cedex 4 (France)
[c] Dr. Y. Champouret, Prof. Dr. M. Etienne
UniversitØ de Toulouse; UPS, INPT, LCC
31077 Toulouse Cedex 4 (France)
E-mail: michel.etienne@lcc-toulouse.fr
[d] Dr. E. lvarez
Instituto de Investigaciones Químicas Isla de la Cartuja
CSIC-Universidad de Sevilla
Avenida de AmØrico Vespucio 49
41092-Sevilla (Spain)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201500776.
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Results and Discussion
Catalytic functionalization of water by carbene insertion
with [TpMsCu(thf)] (1)
Previous works from this laboratory demonstrated the catalytic
capabilities of the complex [TpMsCu(thf)] (1) for the cyclopropa-
nation of olefins as well as the functionalization of CÀH, NÀH,
and OÀH bonds with ethyl diazoacetate (EDA) as the carbene
source.[11] Interestingly, when we performed the reaction of
EDA with water in the presence of catalytic amounts of 1, the
major products were diethyl fumarate and maleate, as a conse-
quence of the catalytic dimerization of the carbene unit. The
insertion product was detected in <2% yield (Scheme 3).
Therefore, we chose a bulkier diazo compound such as ethyl
2-phenyldiazoacetate, N2C(Ph)(CO2Et) (Pheda), with the aim of
disfavoring this dimerization reaction. Gratifyingly, the insertion
of the C(Ph)(CO2Et) unit into the OÀH bond of water yielded
the main product of the reaction (Scheme 3), providing
a model system for our mechanistic study. The reaction was
performed at room temperature and took place in 2 h.
Isolation of the diazo adduct [TpMsCu{h1-N2C(Ph)(CO2Et)}]
(2a)
Scheme 2. Top: General catalytic cycle for the copper-catalyzed XÀH inser-
tion reaction. Bottom: The unique examples of copper–carbene intermedi-
ates relevant in carbene transfer from diazo compounds to olefins.
Once we had demonstrated the ability of complex 1 to pro-
mote the model reaction of Pheda and H2O, we examined the
reaction of 1 with Pheda at low temperature (Scheme 4). When
an equimolar mixture of both reagents in toluene was stirred
at À358C, a smooth change in color from orange to reddish
was observed, but no nitrogen evolution was noted. The addi-
tion of petroleum ether and storing at À308C overnight pro-
Scheme 3. Water functionalization by carbene insertion catalyzed by
[TpMsCu(thf)]. Yields determined by using NMR spectroscopy with an internal
standard.
ethyl 2-phenyldiazoacetate with water by using [TpMsCu(thf)]
(1) and related [TpxCu(L)] complexes (Scheme 3) as catalyst
precursors. We successfully characterized the copper–carbene
intermediate as well as the catalyst dormant species, a diazo–
copper complex. NMR spectroscopy and kinetic studies have
provided valuable information to build a reasonable mechanis-
tic proposal.
Scheme 4. Formation of the copper–diazo compound adducts 2a–d.
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vided red microcrystals of a new complex that showed absorp-
tion at 2046 cmÀ1 in the FTIR spectrum, which was due to a co-
ordinated N2 group (free Pheda shows this band at 2089 cmÀ1).
Multinuclear NMR data were consistent with the presence of
the TpMs ligand and a C(Ph)CO2Et moiety. The observation of
a single set of resonances of the former assessed the existence
of a local C3 symmetry for 2a in solution. The use of 13C-la-
belled N2=13C(Ph)(CO2Et) gave additional information. A reso-
nance centered at d=67.9 ppm in the 13C{1H} NMR spectrum
was assigned to the diazo carbon atom (free Pheda shows this
peak at d=63.1 ppm). On these bases, we propose that com-
plex 2a is formed upon coordination of Pheda to the TpMsCu
core (Scheme 4). The molecular structure of 2a has been eluci-
dated by using an X-ray diffraction study (Figure 1), confirming
Cu(1) angle slightly deviates from linearity [161.17(13)8]. Never-
theless, these data show that both N(7) and N(8) present sp
hybridization (see the Supporting Information for full descrip-
tion of the crystal structure).
Three other copper–diazo adducts have been generated in
situ upon the direct reaction of N2=13C(Ph)(CO2Et) with
the complexes [TpiPr2Cu(CH3CN)], [(Tp*Cu)2] and [(F12-
Tp4Bo,3Ph)Cu(acetone)] (Scheme 4). The new complexes
[TpxCu{h1-N213C(Ph)(CO2Et)}] (Tpx =TpMe2, 2b; TpiPr2, 2c; F12-
Tp4Bo,3Ph, 2d) were detected in solution below room tempera-
ture by using 13C{1H} NMR spectroscopy showing the resonan-
ces of the diazo carbon at d=67.7, 67.3, and 66.9 ppm, respec-
tively. These compounds will be of interest in the generation
of the copper–carbenes described below.
In situ generation and characterization of the copper car-
bene complexes [TpxCu=C(Ph)(CO2Et)] (3)
When a CH2Cl2 solution of 1 and 3 equiv of Pheda prepared at
À308C was allowed to reach room temperature, the color
changed from reddish to dark brown and then to dark orange.
NMR studies of the final mixture showed a combination of
products including 1) (Ph)(OH)CH(CO2Et) resulting from the in-
sertion of the C(Ph)(CO2Et) unit into the OÀH bond of adventi-
tious water, 2) the olefins resulting from carbene coupling, E-
and Z-(Ph)(CO2Et)C=C(Ph)(CO2Et), and 3) the azine EtO2C(Ph)C=
NÀN=C(Ph)CO2Et (Scheme 5).[13] Monitoring the reaction by
Figure 1. Molecular structure of [TpMsCu{h1-N2C(Ph)(CO2Et)}] (2a) (30% dis-
placement ellipsoids; hydrogen atoms have been omitted except for the
one bound to the boron atom).
our proposal: Complex TpMsCu[h1-N2C(Ph)(CO2Et)] contains the
diazo compound bound to the metal center in a terminal fash-
ion.
Examples of copper(I) diazo compound adducts with the
diazo functionality bonded in a h1-fashion are scarce. To the
best of our knowledge, there are only two examples in which
the copper is supported by a bis(phosphino)borate ligand:
[Ph2B(CH2PtBu2)2]Cu([h1-N2C(SiMe3)2] and Ph2B(CH2PtBu2)2]Cu
([h1-N2CMes2]. Geometry around the metal center is trigonal
planar, at variance with that in 2a, in which the k3 coordina-
tion of the TpMs ligand ensures a tetrahedral geometry. There-
fore, complex 2a is the first example of a h1-N-diazo com-
pound adduct in such an environment. The Pheda ligand be-
haves as a s-donor ligand without significant contribution of
p-back-bonding from the metal to the diazoalkane ligand,[12] as
inferred from the structural data: the N(7)-N(8) [1.1371(18) Š]
and N(8)-C(38) [1.322(2) Š] bond lengths and the N(7)-N(8)-
C(38) angle [178.59(17)8] for 2a are comparable to the corre-
sponding values found for free phenyldiazoacetates, a feature
also observed in the trigonal planar complexes mentioned
above. As for [{Ph2B(CH2PtBu2)2}Cu{h1-N2CMes2}], the N(8)-N(7)-
Scheme 5. The reaction of Pheda and complex 1 and the different species
observed by 13C{1H} NMR spectroscopy at different temperatures.
using 13C{1H} NMR spectroscopy in CD2Cl2 showed that at
À408C only the resonances assigned to the diazo adduct 2a
(13C-enriched) were observed. The temperature was then pro-
gressively increased and, at +108C, a new resonance raised at
d=248.5 ppm, which was assigned to the carbene carbon of
the complex [TpMsCu=13C(Ph)(CO2Et)] (3a) on the basis of the
previously described copper carbenes by the groups of Hof-
mann (Scheme 2a, d=229.9 ppm),[10a] Barluenga (Scheme 2b,
d=276.5 ppm),[10b] and Warren (Scheme 2c, d=253.1 ppm).[10b]
Above that temperature, reactions with adventitious water or
the free diazo compound took place leading to the aforemen-
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tioned mixture of products. Other resonances of the TpMs
ligand and C(Ph)(CO2Et) fragment were also observed (see the
Supporting Information).
The observation of the carbenic resonance was not exclusive
of the TpMs-containing copper complex. Following the same
procedure, the three other TpxCu complexes (see Scheme 4)
behaved similarly leading to the formation of the correspond-
ing copper–carbene complexes [TpxCu=13C(Ph)(CO2Et)] (Tpx =
TpMe2, 3b; TpiPr2, 3c; F12-Tp4Bo,3Ph, 3d). Figure 2 shows the
Figure 3. Plot of the chemical shift of the carbene atom in complexes 3a–d
versus the n(CO) value in the corresponding [TpxCu(CO)].
Figure 4. A simplified comparison of the bonding of the MÀCO and MÀCR2
moieties.
The nature of the Tpx ligand affects the electron density at the
metal center in the much same way in both cases.
Figure 2. 13C NMR region for the carbene carbon resonances of complexes
3a–d.
It is the first time that four-coordinate tetrahedral copper–
carbene complexes such as 3a–d have been detected; previ-
ous examples (see Scheme 2)[10] are reduced to trigonal planar
geometries with bi- or monodentate ancillary ligands. Howev-
er, attempts to grow single crystals of 3a–d suitable for X-ray
diffraction study proved unsuccessful because of the poor sta-
bilities of these complexes.
downfield region of the 13C NMR spectra in which the carbenic
carbon resonates (13C-labelled Pheda was employed in all
cases). The chemical shift increased in the order TpiPr2 <TpMe2
TpMs <F12-Tp4Bo,3Ph. Interestingly, we have found that there is
a good linear correlation between the values of n(CO) of the
[TpxCu(CO)] complexes and the chemical shift of the carbenic
carbon (Table 1 and Figure 3). Thus, a decrease of electron den-
sity at the metal center when using poorly donating Tpx li-
gands induces a deshielding of the carbene carbon and, conse-
quently, the corresponding peak appears at higher frequency.
<
Kinetic studies of the reaction of Pheda and H2O catalyzed
by [TpMsCu(thf)] (1)
We have carried out kinetic studies based on the measurement
of the evolution of dinitrogen during the catalytic reaction of
This is reminiscent of the related nature of the MÀCO and MÀ Pheda and H2O by using 1 as the catalyst precursor. When
CR2 bonding, with s donation from the ligand to the metal
and p back-donation from the metal to the ligand (Figure 4).
a 1:10:90 mixture of 1/Pheda/H2O (referred to 0.01 mmol of 1)
was reacted at 258C, a smooth reaction took place in which
gas evolution was detected (see the Supporting Information
for technical details) as shown in Figure 5. Fitting the experi-
mental data into an exponential growth function led to the
value of kobs for this experiment. With this methodology, we
have performed a series of experiments in which the relative
amounts of catalyst, Pheda, H2O, and temperature have been
varied. Table 2 contains all the collected data, from which
some trends can be extracted. First, Pheda inhibits the reaction
as the rate decreases when the concentration of Pheda in-
creases (Table 2, entries 1–3); we suggest this is the result of
Table 1. Values of n(CO)[14] in [TpxCu(CO)] and dCcarbene in complexes 3a–
d.
Tpx Ligand
n(CO) in [TpxCu(CO)]
dCcarbene
[ppm]
[cmÀ1
]
TpiPr2
2056
2060
2079
2113
233.9
236.8
248.5
268.4
Tp*
TpMs
F12-Tp4Bo,3Ph
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Figure 6. Eyring plot for the reaction of Pheda and H2O using [TpMsCu(thf)]
(1) as the catalyst.
Figure 5. Nitrogen evolution in the reaction of Pheda and H2O using
[TpMsCu(thf)] (1) as the catalyst.
lyzed CÀH insertion reaction of EDA into dioxane and postulat-
ed that the large negative entropy of activation
(À25 calmolÀ1 KÀ1) for this reaction could be attributed to
a rate-determining step that would not involve dinitrogen loss
along the lines we observe here. Regarding the DH° value of
10.3(1) kcalmolÀ1, the mentioned previous work provided simi-
lar values (16.4[16] and 19.1[15] kcalmolÀ1].
Table 2. Kinetic experiments of the reaction of Pheda and H2O using
[TpMsCu(thf)] (1) as the catalyst.[a]
Entry
1
Pheda
[equiv]
H2O
[equiv]
T
[K]
kobs
[minÀ1
]
[equiv][b]
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
10
30
60
30
30
10
10
10
10
90
90
90
180
270
40
40
40
298
298
298
298
298
278
288
298
308
6.27(2)”10À4
5.04(9)”10À4
3.96(2)”10À4
4.40(6)”10À4
4.59(6)”10À4
8.82(9)”10À5
2.77(6)”10À4
3.77(3)”10À4
5.41(2)”10À4
We have also employed the isolated copper diazo adduct
2a to monitor dinitrogen evolution. When a solution of 2a in
CD2Cl2 ([2a]=7.8”10À3 m) was stirred at 58C, dinitrogen evolu-
tion was observed immediately, and ceased after 4–5 min (see
the Supporting Information for kinetic curves). NMR studies of
the reaction mixture revealed the formation of the product re-
sulting from insertion of the carbene in the OÀH bond of
water in the purposely wet solvent. A small amount of free
diazo compound that co-crystallized with complex 2a was
quantified as 15% relative to the copper complex. In spite of
that, the reaction was quite fast; a larger amount of Pheda
being required to slow down the reaction rate, because it
occurs under catalytic conditions. The experimental data sup-
port the proposal of 2a being the catalyst resting state, yet
acting as a dormant species. It is the dissociation equilibrium
2a–4 that regulates the amount of [TpMsCu] (4) delivered into
the catalytic cycle to effectively promote the OÀH functionali-
zation.
40
[a] See the Supporting Information for the experimental details. [b] Refers
to 0.01 mmol of catalyst.
the formation of the diazo adduct 2a. Secondly, the variation
of [H2O] does not seem to have any influence on the nitrogen
evolution (Table 2, entries 2, 4, and 5). Therefore, dinitrogen ex-
trusion and copper–carbene formation must occur prior to any
interaction with water, as expected. More interestingly, this
also demonstrates that the formation of the [TpMsCu(OH2)]
adduct is not favored, otherwise the amount of active copper
species would be reduced and the reaction rate affected by
[H2O].
The effect of the temperature on this transformation has
also been studied (Table 2, entries 6–9), leading to the Eyring
plot shown in Figure 6, from which the activation parameters
have been obtained. DH° and DS° were determined as
10.3(1) kcalmolÀ1 and À47.4(4) calmolÀ1 KÀ1, respectively, point-
ing to an associative nature of the key step in the catalytic
cycle. The negative value of activation entropy finds prece-
dents in the literature. Kochi and Salomon reported a value of
DS° =À8.90 calmolÀ1 KÀ1 for the cyclopropanation of 1-hexene
with EDA catalyzed by CuIOTf, although such value was attrib-
uted to the coordination of the olefin.[15] Warren and co-work-
ers described similar values for the reaction of the copper–car-
bene [(NN)Cu=CPh2] with styrene.[10c] Alonso and García deter-
mined[16] the kinetic parameters for the rhodium acetate-cata-
Mechanistic proposal
On the basis of the collected data, an overall mechanistic pic-
ture can be built, as shown in Scheme 6. The catalyst precursor
1 readily dissociates the thf ligand to generate an unsaturated
[TpMsCu] (4) intermediate that is trapped by Pheda to afford
the adduct 2a. The intermediate 4, similar to other species
that have been postulated by means of DFT calculations,[17] can
coordinate the diazo reagent by the diazo carbon atom lead-
ing to 5. This is very likely a less favorable process than the
former; if not, the dinitrogen evolution would be accelerated
when increasing [Pheda], opposite to the experimental obser-
vation. In the absence of free Pheda, H2O functionalization is
fast, implying that the equilibria between 2a, 4, and 5 ensures
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of the new complex 1d is described below. NMR spectra were re-
corded on Agilent 400 MR, Agilent 500 DD2, Bruker Avance 300,
400, or 500 spectrometers. FTIR spectra were recorded on a Nicolet
1
IR200 FTIR spectrometer. H and 13C NMR shifts were measured rel-
ative to deuterated solvents peaks but are reported relative to tet-
ramethylsilane. 19F NMR chemical shifts are reported relative to ex-
ternal CFCl3. Elemental analyses were performed on a PerkinElmer
Series II CHNS/O Analyzer 2400. Dinitrogen evolution was recorded
using a Man on the Moon Tech X201 Kinetic Kit.
Syntheses
TpMsCu[h1-N2C(Ph)(CO2Et)] (2a): The complex [TpMsCu(thf)]
(0.14 mmol) was dissolved in toluene (5 mL) in a Schlenk tube.
Ethyl 2-diazo-2-phenyl acetate (0.14 mmol) was added at À358C.
The reaction was stirred at À358C for 1 h. Complex 2a was isolat-
ed as a red solid from toluene/petroleum ether (1:2) at À308C.
1H NMR (500 MHz, À408C, CD2Cl2): d=1.26 (t, J=7.1 Hz, 3H,
OCH2CH3),1.88 (s, 18H, CH3), 2.04 (s, 9H, CH3), 4.15 (q, J=6.9 Hz,
2H, OCH2CH3), 6.08 (brs,3H, CHpyrazol), 6.63 (brs, 6H, CHmesityl), 7.16
(m, 3H, CHphenyl), 7.23 (t, J=7.3 Hz, 2H, CHphenyl), 7.82 ppm (brs, 3H,
CHpyrazol); 13C{1H} NMR (125 MHz, À408C, CD2Cl2): d=15.1
(OCH2CH3), 20.4 (CH3mesityl), 21.0 (CH3mesityl), 60.6 (OCH2), 105.0
(CHpyrazol), 128.2 (CHmesityl), 125.3 (CHphenyl), 128.5 (CHphenyl), 129.0
(CHphenyl), 130.3 (Cqmesityl), 135.0 (CHpyrazol), 136.9 (Cqmesityl), 137.4
(Cqmesityl), 138.1 (Cqpyrazol), 150.8 (Cphenyl), 163.2 ppm (C=O); IR (KBr):
Scheme 6. The catalytic cycle of the TpMsCu-catalyzed OH functionalization
by carbene insertion with N2=C(Ph)(CO2Et).
enough amount of the latter to generate the copper–carbene
3a. Recall that 3a is quantitatively generated in situ with just
3 equiv of Pheda related to 1. The observation of a negative
value of the activation entropy can be explained in terms of
the formation of 5 from 4.
The final step of the interaction of the copper–carbene 3a
with H2O would be the electrophilic attack of the carbene
ligand to the oxygen atom, generating an ylidic-type of inter-
mediate, from which the product would evolve. The formation
of such species in several TpxCu-catalyzed carbene transfer re-
actions involving heteroatoms have been invoked from DFT
calculations.[18] It has also been proposed[19] that the process
might occur with the intermediacy of more than one molecule
of H2O, although at this stage we have not obtained any evi-
dence for that in our system.
n˜ =2046 (nN2) cmÀ1
F12-Tp4Bo,3PhCu(acetone) (1d): Tl(F12-Tp4Bo,3Ph [21d]
.
)
(0.505 mg,
0.5 mmol) and CuI (0.114 mg, 0.6 mmol) were placed in a Schlenk
flask and acetone (25 mL) was added under stirring. After stirring
overnight, the solvent was removed under vacuum to afford
a yellow solid. The yellow solid was then placed in CH2Cl2 (10 mL),
filtered over Celite, and the solvent was removed under vacuum.
The solid was crystallized from dichloromethane at À258C to give
colorless microcrystalline solid of F12-Tp4Bo,3PhCu(acetone) (1d)
(140 mg, 30%). 1H NMR (500 MHz, 258C, CD2Cl2): d=1.74 (s, 6H,
CH3COCH3), 7.48–7.72 (m, 15H, 3 CHphenyl). 13C{1H} NMR (125 MHz,
258C, CD2Cl2): d=30.2 (CH3COCH3), 108.5 (d, J=16 Hz, Cindazol),
128.2 (Cphenyl), 129.2 (Cphenyl), 129.5 (Cphenyl), 131.0 (m, Cindazol), 131.3
(Cphenyl), 134.4 (dd, J=250, 10 Hz, CFindazol), 134.8 (ddd, J=243, 16,
15 Hz, CFindazol), 139.0 (dd, J=256, 11 Hz, CFindazol), 140.5 (ddd, J=
Conclusion
We have studied the catalytic functionalization of the OÀH
bond of H2O by using the copper–catalyzed transfer and inser-
tion of a carbene C(Ph)(CO2Et) group with N2C(Ph)(CO2Et) as
the carbene source, and the complex [TpMsCu(thf)] (1). The 247, 16, 15 Hz, CFindazol), 145.1 ppm (Cindazol). The 13C peak of the car-
bonyl of acetone could not be detected. 19F NMR (282 MHz, 258C,
presence of a four-coordinate tetrahedral copper–carbene in-
termediate [TpxCu=C(Ph)(CO2Et)] has been demonstrated. The
diazo complex [TpMsCu{h1-N2=C(Ph)(CO2Et)}] has been isolated
and structurally characterized. Kinetic studies have shown that
this compound is a dormant species and constitutes the rest-
ing state of the catalyst in this system.
CD2Cl2): d=À166.8 (t, J=20 Hz, CFindazol), À157.6 (t, J=20 Hz,
CFindazol), À153.3 (m, CFindazol), À146.0 ppm (t, J=20 Hz, CFindazol); ele-
mental analysis calcd (%) for C42H22BCuF12N6O (929.02 gmolÀ1): C
54.30, H 2.39, N 9.05; found: C 54.09, H 2.00, N 9.00.
Reaction of TpMsCu(thf) and 13C-labeled ethyl 2-diazo-2-phenyla-
cetate: Detection of [TpMsCu{h1-N213C(Ph)(CO2Et)}] (2a) and
[TpMsCu=13C(Ph)(COOEt)] (3a): A solution of [TpMsCu(thf)] (12 mg,
0.017 mmol) in CD2Cl2 (0.5 mL) was transferred to a NMR tube that
was sealed with a Teflon stopper and was cooled at À408C. 140 mL
of a stock solution of the diazo compound and 13C2-labelled ethyl
2-diazo-2-phenylacetate (0.35m in CD2Cl2) were then added. The
Experimental Section
General methods
All reactions and manipulations were carried out under a dinitrogen reaction mixture was monitored by using NMR spectroscopy from
or argon atmosphere by using standard Schlenk techniques or À40 to +108C. Selected peaks in the 13C{1H} NMR spectrum of the
under nitrogen or argon atmosphere in an Mbraun or Jacomex reaction mixture (125 MHz, CD2Cl2): At À408C, d=67.9 ppm (N213C)
glovebox, respectively. All substrates were purchased from Aldrich for 2a; at +108C, d=248.5 (Cu=13C) for 3a, 162.5 [azine,
and used without further purification. Solvents were distilled and (EtO2C)(Ph)13C=NÀN=13C(Ph)(CO2Et)], 137.3 (diethyl 2,3-diphenylma-
degassed before use. The diazo compound N2C(Ph)(CO2Et),[20] in- leate, 13C=13C), 72.7 ppm (ethyl mandelate,13CH=OH). The same
cluding the 13C-labelled sample, the homoscorpionate ligands procedure was applied with the other TpxCu complexes to observe
(TpMs, Tp*, TpiPr2, and F12-Tp4Bo,3Ph [21]
)
as well as their complexes[14] the copper–carbenes 3b–d. See the Supporting Information for
were prepared according to the literature methods. The synthesis spectra and details.
Chem. Eur. J. 2015, 21, 9769 – 9775
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Full Paper
B. Neelima, C. V. Reddy, J. Mol. Catal. A 2006, 256, 269–272; d) L. K. Bau-
mann, H. M. Mbuvi, G. Mbuvi, G. Du, L. K. Woo, Organometallics 2007,
26, 3995–4002; e) P. Le Maux, I. Nicolas, S. Chevance, G. Simonneaux,
Tetrahedron 2010, 66, 4462–4468.
Kinetic studies on the carbene insertion into OÀH bond using
Pheda as the diazo compound and [TpMsCu(thf)] (1) as the cata-
lyst precursor: Nitrogen evolution measurements were performed
by using a device consisting of a stainless-steel gas reservoir
doubly connected to a pressure transmitter, and an electronic pres-
sure meter/controller (EL-Press, Bronkhorst HI-TEC). The outlet of
the pressure controller was connected to a 100 mL reaction flask,
also connected to a Schlenk manifold to allow for manipulation of
the reaction and degassing. The N2 pressure increase was mea-
sured after addition of Pheda (0.1 mmol) to a stirred solution of
H2O (0.4 mmol) and [TpMsCu(thf)] (0.01 mmol) in CH2Cl2 (2 mL) at
a fixed temperature. The mixture appeared homogenous in all
cases. See the Supporting Information for technical details.
[6] a) A. F. Noels, A. Demonceau, N. Petiniot, A. Hubert, P. Teyssie, Tetrahe-
dron 1982, 38, 2733–2739; b) D. J. Miller, C. J. Moody, Tetrahedron 1995,
51, 10811–10843.
[7] a) H. M. L. Davies, T. Hansen, M. R. Churchill, J. Am. Chem. Soc. 2000,
122, 3063–3070; b) H.-Y. Thu, G.-M. Tong, J.-S. Huang, S. L.-F. Chan, Q.-H.
Deng, C.-M. Che, Angew. Chem. Int. Ed. 2008, 47, 9747–9751; Angew.
Chem. 2008, 120, 9893–9897.
[8] a) S. Bachmann, D. Fielenbach, K. A. Jørgensen, Org. Biomol. Chem.
2004, 2, 3044–3049; b) B. Liu, S. F. Zhu, W. Z. C. Chen, Q. L. Zhou, J. Am.
Chem. Soc. 2007, 129, 5834–5835; c) B. Xu, S. F. Zhu, X. L. Xie, J. J. Shen,
Q. L. Zhou, Angew. Chem. Int. Ed. 2011, 50, 11483–11486; Angew. Chem.
2011, 123, 11685–11688.
Crystal X-ray structure analysis for 2a
[9] a) T. C. Maier, G. C. Fu, J. Am. Chem. Soc. 2006, 128, 4594–4595; b) S.-F.
Zhu, Y. C. C. Chen, Q.-L. Zhou, Angew. Chem. Int. Ed. 2008, 47, 932–934;
Angew. Chem. 2008, 120, 946–948.
Crystal of suitable of size for X-ray diffraction analysis was coated
with dry perfluoropolyether and mounted on glass fibers and fixed
in a cold nitrogen stream (T=100 K) to the goniometer head. Data
collection was performed on a Bruker-Nonius X8Apex-II CCD dif-
fractometer, using monochromatic radiation l(MoKa)=0.71073 Š,
by means of w and f scans with a width of 0.50 degree. The data
were reduced (SAINT)[22] and corrected for absorption effects by
the multi-scan method (SADABS).[23] The structures were solved by
direct methods (SIR-2002)[24] and refined against all F2 data by full-
matrix least-squares techniques (SHELXTL-6.12)[25] minimizing
[10] a) B. F. Straub, P. Hofmann, Angew. Chem. Int. Ed. 2001, 40, 1288–1290;
Angew. Chem. 2001, 113, 1328–1330; b) J. Barluenga, L. A. López, O.
Lçber, M. Tomµs, S. García-Granda, C. lvarez-Rffla, J. Borge, Angew.
Chem. Int. Ed. 2001, 40, 3392–3394; Angew. Chem. 2001, 113, 3495–
3497; c) X. L. Dai, T. H. Warren, J. Am. Chem. Soc. 2004, 126, 10085–
10094; d) N. Mankad, J. N. Peters, Chem. Commun. 2008, 1061–1063.
[11] a) M. M. Díaz-Requejo, A. Caballero, T. R. Belderrain, M. C. Nicasio, S. Tro-
fimenko, P. J. PØrez, J. Am. Chem. Soc. 2002, 124, 978–983; b) M. M.
Díaz-Requejo, T. R. Belderrain, M. C. Nicasio, S. Trofimenko, P. J. PØrez, J.
Am. Chem. Soc. 2002, 124, 896–897; c) M. E. Morilla, M. J. Molina, M. M.
Díaz-Requejo, T. R. Belderrain, M. C. Nicasio, S. Trofimenko, P. J. PØrez, Or-
ganometallics 2003, 22, 2914–2918.
[12] J. Egloff, M. Ranocchiari, A. Schira, C. Schotes, A. Mezzetti, Organometal-
lics 2013, 32, 4690–4701, and references therein.
[13] Previous work from our laboratory proposed mechanistic pathways
leading to the carbene coupling and azine formation; see: I. Rivilla,
W. M. C. Sameera, E. Alvarez, M. M. Díaz-Requejo, F. Maseras, P. J. PØrez,
Dalton Trans. 2013, 42, 4132–4138.
w[Fo ÀFc2]2. All the non-hydrogen atoms were refined anisotropical-
2
ly. The hydrogen atoms were placed in geometrically calculated
positions using a riding model.
CCDC 1045503 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[14] a) C. Mealli, C. S. Arcus, J. L. Wilkinson, T. J. Marks, J. A. Ibers, J. Am.
Chem. Soc. 1976, 98, 711 –718; b) J. L. Schneider, S. M. Carrier, C. E. Rug-
giero, V. G. Young, W. B. Tolman, J. Am. Chem. Soc. 1998, 120, 11408–
11418; c) K. Fujisawa, T. Ono, Y. Ishikawa, N. Amir, Y. Miyashita, K.-I. Oka-
moto, N. Lehnert, Inorg. Chem. 2006, 45, 1698–1713; d) see the Sup-
porting Information.
[15] R. G. Salomon, J. K. Kochi, J. Am. Chem. Soc. 1973, 95, 3300–3310.
[16] M. E. Alonso, M. C. García, Tetrahedron 1989, 45, 69–76.
[17] See, for example: J. M. MuÇoz-Molina, W. M. C. Sameera, E. lvarez, F.
Maseras, T. R. Belderraín, P. J. PØrez, Inorg. Chem. 2011, 50, 2458–2467.
[18] a) J. Urbano, A. A. C. Braga, F. Maseras, E. lvarez, M. M. Díaz-Requejo,
P. J. PØrez, Organometallics 2009, 28, 5968–5981; b) M. Corro, M.
Besora, C. Maya, E. lvarez, J. Urbano, M. R. Fructos, F. Maseras, P. J.
PØrez, ACS Catal. 2014, 4, 4215–4222.
Acknowledgements
Support for this work was provided by the MINECO (CTQ2011-
28942-CO2-01, CTQ2014-52769-C3-1-R and CTQ2011-24502)
and the Junta de Andalucía (P10-FQM-06292). A.P. thanks MEC
for FPU fellowship. Y.C. and M.E. thank the Institut de Chimie
of the CNRS for support. Dr. Christian Bijani (LCC) is acknowl-
edged for the low-temperature NMR studies.
Keywords: carbenes · copper · diazo compounds · ligands ·
[19] Y. Liang, H. Zhou, Z.-X. Yu, J. Am. Chem. Soc. 2009, 131, 17783–17785.
[20] a) M. Ranocchiari, A. Mezzetti, Organometallics 2009, 28, 3611–3613;
b) C. Peng, J. Cheng, J. Wang, J. Am. Chem. Soc. 2007, 129, 8708–8709.
[21] a) TpMs: A. L. Rheingold, C. B. White, S. Trofimenko, Inorg. Chem. 1993,
32, 3471–3477; b) Tp*: S. Trofimenko, J. Am. Chem. Soc. 1967, 89,
3170–3177; c) TpiPr2: N. Kitajima, K. Fujisawa, C. Fujimoto, Y. Moro-oka,
S. Hashimoto, T. Kitagawa, K. Toriumi, K. Tatsumi, A. Nakamura, J. Am.
Chem. Soc. 1992, 114, 1277–1291; d) F12-Tp4Bo,3Ph: W.-S. Ojo, K. Jacob, E.
Despagnet-Ayoub, B. K. MuÇoz, S. Gonell, L. Vendier, V.-H. Nguyen, M.
Etienne, Inorg. Chem. 2012, 51, 2893–2901.
NMR spectroscopy
[1] a) T. Ye, M. A. McKervey, Chem. Rev. 1994, 94, 1091–1160; b) M. P. Doyle,
T. Ye, M. A. McKervey, Modern Catalytic Methods for Organic Synthesis
with Diazo Compounds, Wiley, New York, 1998; c) M. P. Doyle, R. Duffy,
M. Ratnikov, Chem. Rev. 2010, 110, 704–724.
[2] D. Gillingham, N. Fei, Chem. Soc. Rev. 2013, 42, 4918–4931.
[3] a) M. M. Diaz-Requejo, A. Caballero, M. R. Fructos, P. J. PØrez in Alkane C-
H Activation by Single-Site Metal Catalysis (Ed.: P. J. PØrez), Springer, Am-
sterdam, 2012, Chapter 6; b) M. M. Díaz-Requejo, P. J. PØrez, Chem. Rev.
2008, 108, 3379–3394; c) M. M. Díaz-Requejo, T. R. Belderraín, M. C. Ni-
casio, P. J. PØrez, Dalton Trans. 2006, 5559–5566.
[22] Bruker (2007), APEX2, Bruker AXS Inc., Madison, Wisconsin, USA.
[23] Bruker (2001), APEX2, Bruker AXS Inc., Madison, Wisconsin, USA.
[24] C. M. Burla, M. Camalli, B. Carrozzini, G. L. Cascarano, C. Giacovazzo, G.
Poliori, R. Spagna, J. Appl. Cryst. 2003, 36, 1103.
[4] A. Caballero, E. Despagnet-Ayoub, M. M. Díaz-Requejo, A. Díaz-Rodrí-
guez, M. E. Gonzµlez-NfflÇez, R. Mello, B. K. MuÇoz, W. Solo Ojo, G. Asen-
sio, M. Etienne, P. J. PØrez, Science 2011, 332, 835–838.
[25] G. M. Sheldrick, Acta Crystallogr. Sect. A 2008, 64, 112–122.
[5] a) M. Yang, X. Wang, H. Li, P. Livant, J. Org. Chem. 2001, 66, 6729–6733;
b) M. E. Morilla, M. M. Díaz-Requejo, T. R. Belderrain, M. C. Nicasio, S. Tro-
fimenko, P. J. PØrez, Chem. Commun. 2002, 2998–2999; c) M. L. Kantam,
Received: February 26, 2015
Published online on May 26, 2015
Chem. Eur. J. 2015, 21, 9769 – 9775
www.chemeurj.org
9775
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim