CuAAC functionalization of azide-tagged copper(I)-NHCs acting as catalyst and substrate

Article abstract of DOI:10.1021/om3005355

Azide-tagged copper(I) complexes of N-heterocyclic carbenes (NHCs) analogous to the well-known bis[2,6-diisopropylphenyl]imidazol-2-ylidene (IPr) and bis[2,6-diisopropylphenyl]imidazolin-2-ylidene (SIPr) were synthesized and characterized. These complexes were able to act as catalyst and substrate in a model copper-catalyzed azide-alkyne (CuAAC) reaction with propargyl alcohol, yielding functionalized copper(I)-NHC complexes.

Full text of DOI:10.1021/om3005355

Article
pubs.acs.org/Organometallics
CuAAC Functionalization of Azide-Tagged Copper(I)-NHCs Acting as
Catalyst and Substrate
Clementine Gibard, Daniel Avignant, Federico Cisnetti,* and Arnaud Gautier*
́
Institut de Chimie de Clermont-Ferrand, CNRS UMR 6296, Universite
France
́ ̀
Blaise Pascal, 24 Avenue des Landais, F-63177 Aubiere,
S
* Supporting Information
ABSTRACT: Azide-tagged copper(I) complexes of N-heterocyclic carbenes (NHCs) analogous to the well-known bis[2,6-
diisopropylphenyl]imidazol-2-ylidene (IPr) and bis[2,6-diisopropylphenyl]imidazolin-2-ylidene (SIPr) were synthesized and
characterized. These complexes were able to act as catalyst and substrate in a model copper-catalyzed azide−alkyne (CuAAC)
reaction with propargyl alcohol, yielding functionalized copper(I)-NHC complexes.
he strong metal−carbon bond of metal N-heterocyclic
Tcarbene (NHC) complexes associated with the remarkable
electron-donating properties of the carbene ligand and their
steric protection of the metal center has allowed them to become
a leading family of contemporary organometallic chemistry.1
Thus, they have attracted considerable interest over the last few
decades, first as laboratory curiosities and later on for their high
catalytic efficiency. It is noteworthy that their use as metal-based
drugs is also being actively explored.2
Therefore, straightforward strategies for the functionalization
of NHC ligands are of importance, as they allow modulation of
solubility, lipophilicity, and reactivity. Indeed, several methods
are now available to synthesize functionalized metal-NHCs.
Resulting structures include chiral metal-NHCs, neutral tethered
oligonuclear NHC complexes, and catalysts decorated with
charged and/or polar groups for solubility modulation.3 Most of
these methods rely on a prefunctionalization strategyi.e., the
imidazol(in)ium precursors are functionalized before the
metalation step. However, postfunctionalization approaches
allow more modular synthetic pathways (Chart 1).
Although azide−alkyne chemistry has allowed numerous
successes in postfunctionalization of coordination or organo-
metallic complexes,4 it has seldom been used on metal-NHCs.
Elsevier and co-workers reported a single example of copper-
catalyzed azide−alkyne cycloaddition (CuAAC) on a palladium
complex precursor to yield 1 (Chart 2).5 Guichard, Bellemin-
Laponnaz, and co-workers were the first to explore in detail the
practicability of a catalytic azide−alkyne postfunctionalization
route for metal-NHCs in order to generate functionalized
complexes such as 2 and 3.6 The ability of the ruthenium
complex Cp*RuCl(PPh3)2 to catalyze the formation of the
triazole as a 1,5-regioisomer7 starting from alkynyl complex
precursors was highlightedhowever, CuAAC reactions were
not successful with their precursors. Importantly, this Ru-
catalyzed strategy allowed the synthesis of biomolecule
conjugates. Recently, we have reported a synthetic strategy
implying azide−alkyne precursors allowing both pre-8,9 and
postfunctionalization.9 In the latter case, the introduction of the
desired functional group is performed by [2 + 3] Huisgen
cycloaddition onto the metal−NHC. The azide-tagged gold(I)−
NHC complex 4 was subjected to a thermal cycloaddition (50
°C, 10 days) with dimethyl acetylenedicarboxylate to yield the
cycloadduct 5. Alternatively, an instantaneous exothermic
reaction was observed with the strained alkyne bicyclo[6.1.0]-
non-4-yn-9-ylmethanol at room temperature, to afford the bis-
triazole gold(I)-NHCs 6.
In our effort to delineate efficient methods to synthesize
functionalized metal-NHCs, we hypothesized that copper(I)-
NHC complexes bearing azide functions could act as both a
catalyst and a substrate in a CuAAC functionalization strategy.
To verify such an assumption, we chose the unsaturated [N,N′-
bis(4-azido-2,6-diisopropylphenyl)imidazol-2-ylidene]-
chlorocopper(I) (7a) and its saturated analogue [N,N′bis(4-
azido-2,6-diisopropylphenyl)imidazolin-2-ylidene]-
chlorocopper(I) (7b), which we reacted with propargyl alcohol
(Chart 3), to exemplify a functionalization allowing both
solubility modulation and the possibility of further modification.
RESULTS AND DISCUSSION
■
The Cu(I)-NHC 7a was straighforwardly obtained by the silver
transmetalation route from the known complex 9a,9 synthesized
from the corresponding imidazolium chloride 8a (Scheme 1).
Special Issue: Copper Organometallic Chemistry
Received: June 15, 2012
Published: August 7, 2012
© 2012 American Chemical Society
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Chart 1. Functionalization Strategies
Chart 2. Postfunctionalization of Metal-NHCs Performed by Azide−Alkyne Chemistry
under vacuumdichloromethane in samples of 7a (this also
applies to 7b). Indeed, electron density corresponding to such a
disordered solvent was detected (see the Experimental Section).
Not unexpectedly, the coordination geometry proved to be very
similar to those of the known [(IPr)CuCl] (10) (Figure 1 and
Table 1).10 The azide groups are found 7.0 Å away from the
copper center. Owing to this distance and to the rigid nature of
the phenylene spacer, these groups are obviously unable to
interact with the copper atom, as expected. Interestingly, azide−
azide dipolar interactions are apparent in the structure packing
(dipole−dipole distances 3.31 and 3.64 Å) and may be partially
responsible for the crystal integrity, as was found for its gold(I)
and silver(I) counterparts.9
Chart 3. Postfunctionalization of Cu-NHCs 7
Scheme 1. Synthetic Route to the Copper-NHC 7a
The synthetic route to 7b, depicted in Scheme 2, starts with
the known diiodoazadiene 11,11 which was reduced according to
a classical procedure to the diamine 12. Introduction of azides
was performed using the copper(I) catalytic system reported by
Andersen et al.12 Cyclization of 13·2HCl using the classical
procedure affords the imidazolinium salt 8b.13 This reaction
sequence was performed on a gram scale with a global yield of
63%. 7b is finally obtained similarly to 7a using silver oxide
metalation followed by copper chloride transmetalation.
In preliminary experiments to synthesize the expected triazole-
decorated Cu-NHCs, the reactions between 7a,b and propargyl
alcohol were examined (Scheme 3). After 2 days in dry DMSO-d6
Gratifying, the Cu(I)-NHC complex 7a is bench-stable for
several months. Slow diffusion of n-pentane in a dichloro-
methane solution at 4 °C affords crystals suitable for X-ray
diffraction. NMR and microanalysis show the presence of
nonvolatilei.e., remaining in the sample after prolonged drying
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at 50 °C, 1H NMR revealed a total lack of reactivity, as was also
observed in CDCl3. However, we found out that the reaction
rates were dramatically increased by the addition of 1% (v/v) of
water into the reaction medium. Indeed, complete disappearance
of both 7a and 7b occurs after an overnight reaction and the
1
single products 14a,b are observed by H NMR in the crude
mixture. The unique reaction productonly the triazole 1,4-
regioisomer is expected to be formed in CuAAC14along with
the result of control experiments15 performed with azolium salts
8a,b instead of the corresponding copper carbenes 7a,b
unambiguously prove the catalytic nature of the reaction. As
the reaction is sterically impossible intramolecularly (see above
for structural discussion), copper complexes catalyze in an
intermolecular fashion their functionalization with alkynes.16 The
necessary presence of water for the reactivity is reminiscent of the
behavior of the water-activated latent catalyst [(SIPr)CuCl]
́
(10b) reported by Dıez-Gonzal
́
ez and Nolan.17 However,
attempts performed with higher water content did not proceed
to completion: 10% (v/v) of water resulted in a significant
amount of imidazol(in)ium byproduct, and “on water”
conditions did not allow any detectable conversion.
1
Comparisons of H NMR spectra between starting materials
7a,b and the products showed a striking difference in the
aromatic part with the emergence of the characteristic singlet of
the triazole moiety and a modification of the aromatic signature
for both complexes. Moreover, the total extinction of the IR
stretching band at 2100 cm−1 confirmed a reaction through the
azide functions. Compounds 14a,b were isolated after
evaporation of the DMSO under high vacuum and precipitation
with ether from an ethanol solution in 75% and 69% yields,
respectively. Importantly, neither NMR spectroscopy nor
elemental analysis allows the determination of the homoleptic
or heteroleptic nature of the complexes and, unfortunately, all
attempts to form crystals suitable for X-ray diffraction were
unsuccessful.
To confirm the neutral nature of the metal-NHCs,
conductivity measurements18 for complexes 14a,b were
performed in DMSO. For the sake of comparison, we measured
under the same conditions the conductivity due to (IPr)CuCl
(10), (SIPr)CuCl, and [(IPr)2Cu]PF6, as well as silver complex
16 and gold complex 17 (Chart 4, Table 2).
Figure 1. Ellipsoid plot of [(IPrN3)CuCl] (7a) (top) and the
corresponding packing diagram (bottom). Ellipsoids are shown at the
50% probability level, and H atoms are omitted for clarity.
Table 1. Selected Bond Lengths (Å) and Angles (deg) in
Copper Complexes 7a and [(IPr)CuCl] (10)
7a
1012
Cu1−C1
N1−C1
N2−C1
C2−C3
Cu1−Cl2
1.886(3)
1.350(4)
1.347(4)
1.310(5)
2.0933(11)
1.953(8)
1.320(7)
1.320(7)
1.368(15)
2.089(4)
N1−C1−N2
C1−Cu1−Cl2
104.4(3)
108.9(6)
180.0
176.46(11)
Scheme 2. Synthetic Route to the Copper-NHC 7b
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Scheme 3. CuAAC Reactions of Complexes 7
Chart 4. Gold(I) and Silver(I) Complexes Related to 7a
a
Table 2. Molar Conductivities ΛM (S cm−2 mol−1) of Solutions of Copper(I)-NHCs in DMSO
14a
14b
(IPr)CuCl
(SIPr)CuCl
[(IPr)2Cu]PF6
16
17
nature
neutral
2.7
neutral
1.2
neutral
0.9
neutral
0.6
cationic
26.419
cationic
20.219
neutral
1.8
ΛM
a
Conditions: T = 20 °C, c = 2.5 × 10−3 M.
Figure 2. Formation of 14a from 7a and propargyl alcohol in DMSO-d6 with 1% H2O at 50 °C as a function of time.
With the carbene ligand kept constant, this set of data is in
agreement with the ionicity of 16 and 17, both of which were
demonstrated independently.9 Therefore, the neutral nature of
14a,b is confirmed.
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(C carbene), 147.5 (C aromatic), 141.3 (C aromatic), 131.2 (C
aromatic), 124.7 (CH imidazole), 114.7 (CH aromatic), 28.5 (CH-
In order to get more information about the reactivity, the
kinetic profiles of functionalization of 7a,b with propargyl alcohol
were studied by 1H NMR at 50 °C in water/DMSO-d6 (1% v/v).
A time-dependent complication of the aromatic region was
observed, associated with the formation of a dissymmetric
compound assignable to the monotriazoles 15a,b. Logically, at
the last stage of the reactions, simplification of the spectra
occurred, due to the formation of the final symmetrical
compounds 14a,b (Figure 2, Scheme 3, and the Supporting
Information).
(CH3)2), 24.0 (CH(CH3)2), 23.0 (CH(CH3)2). IR: ν
̃
(cm−1) 2964,
2112 (N3), 1597, 1472, 1337, 1310, 1280, 1240. HRMS (ESI+):
calculated for C29H37CuN9 [M − (Cl + CH3CN)]+ 574.2468, found
574.2455. Anal. Found: C, 53.83; H, 5.75; N, 17.70. Calcd for
C27H34ClCuN8·0.5CH2Cl2: C, 53.96; H, 5.76; N, 18.28.
Synthesis of Diiododiamine 12. Azadiene 11 (10.6 g, 16.9 mmol)
was dissolved in 75 mL of a 6/4 THF/MeOH mixture. NaBH4 (639 mg,
16.9 mmol) was added cautiously in portions to this solution. After 2 h,
TLC analysis (1/1 ethyl acetate/cyclohexane) indicated the total
disappearance of 11 and the formation of a single product. The excess
NaBH4 was quenched by addition of saturated aqueous NH4Cl while
keeping the temperature at room temperature with a cool water bath.
Organic solvents were evaporated, and the resulting aqueous slurry was
extracted with 3 × 50 mL of Et2O. The joint organic phases were dried
over MgSO4 and evaporated, yielding 10.07 g (96%) of 12 as an off-
white crystalline solid. 1H NMR (400 MHz, CDCl3, ppm): δ 7.42 (s, 4H,
CH aromatic), 3.28 (hept, J = 6.8 Hz, 4H, CH(CH3)2), 3.14 (s; 4H,
CH2), 1.31 (d, J = 6.8 Hz, 12H, CH(CH3)2), 1.26 (d, J = 6.8 Hz, 12H,
CH(CH3)2). 13C{1H} NMR (100 MHz, CDCl3, ppm): δ 145.3 (C
aromatic), 143.1 (C aromatic), 133.7 (CH aromatic), 88.9 (CI), 52.1
SUMMARY
■
Two copper(I) N-heterocyclic carbenes bearing azide functions
were synthesized and characterized. For this purpose, an efficient
and gram-scale synthesis route to a azide-tagged saturated
imidazoliniun salt was developed, starting from easily accessible
compounds. The azido complexes undergo a CuAAC reaction
without the need for any additional copper(I) source, thus
leading to a process usable in the postfunctionalization context.
In addition to the few other metal-NHC postfunctionalization
reactions reported to date, this process could pave the way for the
synthesis of a library of copper(I) complexes using a modular
approach. Further studies in this direction are ongoing in our
laboratory.
(CH2), 27.9 (CH(CH3)2), 24.2 (CH(CH3)2). IR: ν
̃
(cm−1) 3367 (NH),
2960, 2861, 1572, 1454, 1331, 1191. HRMS (ESI+): calcd for
C26H39N2I2 [M + H]+ 633.1203, found 633.1198. Anal. Found: C,
49.58; H, 6.12; N 4.42. Calcd for C26H38I2N2: C, 49.38; H, 6.06; N, 4.43.
Synthesis of Diazidodiamine 13. 12 (8.53 g, 13.5 mmol), NaN3
(3.51 g, 54 mmol), N,N′-dimethylethane-1,2-diamine (218 μL, 2.03
mmol, 15 mol %), and sodium ascorbate (267 mg, 1.35 mmol, 10 mol
%) were added to 200 mL of a 9/1 DMSO/H2O mixture. The resulting
solution was deoxygenated under a flux of Ar. Copper(I) iodide (1.35
mmol, 10 mol %) was then added, and the mixture was stirred for 7 h at
70 °C in the dark. The reaction mixture was poured on 300 mL of ice−
water, and 13 was recovered as a brown powder after filtration, washing
with water, and desiccation. Yield: 5.42 g (87%). 1H NMR (400 MHz,
CDCl3, ppm): δ 7.42 (s, 4H, CH aromatic), 3.28 (hept, J = 6.8 Hz, 4H,
CH(CH3)2), 3.14 (s; 4H, CH2), 1.31 (d, J = 6.8 Hz, 12H, CH(CH3)2),
1.26 (d, J = 6.8 Hz, 12H, CH(CH3)2). 13C{1H} NMR (100 MHz,
CDCl3, ppm): δ 144.8 (C aromatic), 140.5 (C aromatic), 135.3 (C
aromatic), 114.4 (CH aromatic), 52.3 (CH2), 28.1 (CH(CH3)2), 24.1
EXPERIMENTAL SECTION
■
General Considerations. NMR spectra for compound character-
ization were recorded in Fourier transform mode with a Bruker
AVANCE 400 spectrometer (1H at 400 MHz, 13C at 100 MHz) at 298
K. Data are reported as chemical shifts (δ) in ppm. The kinetic survey of
CuAAC reactions was performed with a Bruker AVANCE 500
spectrometer (1H at 500 MHz). Residual solvent signals were used as
internal references (1H, 13C). Electrospray (positive mode) high-
resolution mass spectra were recorded on a Q-TOF micro spectrometer
(Waters), using internal (H3PO4) and external lock masses (leucine-
enkephalin [M + H]+: m/z 556.2766). IR spectra were recorded on a
Shimadzu FTIR-8400S Fourier transform infrared spectrophotometer.
Elemental analyses were performed at the Service de Microanalyse,
(CH(CH3)2). IR: ν
̃
(cm−1) 3354 (NH), 2969, 2931, 2101 (N3), 1598,
1463, 1336, 1242. HRMS (ESI+): calculated for C26H39N8 [M + H]+
463.3298, found 463.3291.
́
Universite de Lorraine, Vandoevre-les-Nancy, France. X-ray diffraction
intensity data were collected at T = 293 K with a Bruker APEX-II CCD
diffractometer (Mo Kα radiation (λ = 0.7107 Å)). The structure was
solved by direct methods with SHELXS-9720 and refined with SHELXL-
9721 implemented in the CRYSTALS program package.22 The
contribution of the highly disordered solvent molecule present in the
lattice was handled by the use of the PLATON/SQUEEZE procedure.23
Conductivity measurements were performed at 20 °C in duplicate with
solutions prepared independently using a Radiometer Analytical
CDM210 conductivity meter equipped with a standard 1 cm
measurement cell. Warning! Organic and inorganic azides may pose safety
concerns due to their potential explosivity. However, none of the organic
azides described herein are considered to be dangerous according to a
commonly accepted rule (NC/NN ≥ 3).24 Compounds 8a,9 9a,9
[(IPr)CuCl] (10),25 [(SIPr)CuCl],17 [(IPr)2Cu](PF6),26 11,11 16,9 and
179 were synthesized using literature procedures.
Synthesis of N,N′-Bis[4-azido-2,6-diisopropylphenyl]-
imidazolinium Chloride (8b). 13 (2.10 g, 4.54 mmol) was treated
with an excess (about 3 equiv) of ethanolic HCl (freshly prepared by the
cautious addition of 1.3 mL of acetyl chloride to 15 mL of absolute
ethanol). After 30 min with vigorous stirring the double chlorhydrate
13·2HCl which separated was recovered by filtration and washed with
cold ethanol. This powder was taken up in 60 mL of a 1/1 HC(OEt3)/
EtOH mixture, which was refluxed for 2 h. After the mixture was cooled
to room temperature and evaporated, the residue was triturated in 30
mL of Et2O. The resulting powder was recovered by filtration, washed
with cold ether, taken up in 5 mL of CH2Cl2, and reprecipitated by the
dropwise addition of 40 mL of n-pentane. Yield: 1.74 g (75%). 1H NMR
(400 MHz, CDCl3, ppm): δ 7.42 (s, 4H, CH aromatic), 3.28 (hept, J =
6.8 Hz, 4H, CH(CH3)2), 3.14 (s; 4H, CH2), 1.31 (d, J = 6.8 Hz, 12H,
CH(CH3)2), 1.26 (d, J = 6.8 Hz, 12H, CH(CH3)2). 13C{1H} NMR (100
MHz, CDCl3, ppm): δ 160.7 (NCHN), 148.4 (C aromatic), 142.1 (C
aromatic), 126.6 (C aromatic), 115.4 (CH aromatic), 53.7 (CH2), 28.5
Synthesis of {N,N′-Bis[4-azido-2,6-diisopropylphenyl]-
imidazol-2-ylidene}chlorocopper(I) (7a). 9a (100 mg, 0.163
mmol) was dissolved in 2 mL of degassed dichloromethane, copper(I)
chloride (47.9 mg, 0.49 mmol) was added, and the mixture was stirred
for 1 h. The resulting suspension was filtered over Celite and the filtrate
evaporated to afford a yellow powder. Yield: 92 mg (92%).
Crystallization conditions for X-ray structural studies: a solution of 7a
(10 mg in 0.5 mL of dichloromethane) was layered with 8 mL of n-
pentane in a test tube which was placed in a closed vessel at 4 °C.
(CH(CH3)2), 24.6 (CH(CH3)2), 23.0 (CH(CH3)2). IR: ν
̃
(cm−1) 2966,
2103 (N3), 1620, 1461, 1337, 1275. HRMS (ESI+): calculated for
C27H37N8 [M]+ 473.3141, found 473.3140. Anal. Found: C, 63.73; H,
7.32; N, 21.59. Calcd for C27H37ClN8: C, 63.70; H, 7.33; N, 22.01.
Synthesis of {N,N′-Bis[4-azido-2,6-diisopropylphenyl]-
imidazolin-2-ylidene}chlorosilver(I) (9b). 8b (500 mg, 0.98
mmol) was dissolved in 40 mL of dichloromethane, silver oxide (147
mg, 0.64 mmol) was added, and the mixture was stirred for 2 h at room
temperature in the dark. The resulting suspension was filtered over
Celite, and the filtrate was evaporated under reduced pressure to afford
1
Monocrystalline prisms were recovered after 3 days. H NMR (400
MHz, DMSO-d6, ppm): δ 7.90 (s, 2H, CH imidazole), 7.10 (s, 4H, CH
aromatic), 2.45 (hept, J = 6.8 Hz, 4H, CH(CH3)2), 1.20 (d, J = 6.8 Hz,
24H, CH(CH3)2). 13C{1H} NMR (100 MHz, DMSO-d6, ppm): δ 178.7
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an off-white powder. Yield: 544 mg (90%). 1H NMR (400 MHz,
DMSO-d6, ppm): δ 7.03 (s, 4H, CH aromatic), 4.12 (s; 4H, CH2) 3.07
(hept, J = 6.8 Hz, 4H, CH(CH3)2), 1.31 (d, J = 6.8 Hz, 12H,
CH(CH3)2), 1.24 (d, J = 6.8 Hz, 12H, CH(CH3)2). 13C{1H} NMR (100
MHz, CDCl3, ppm): δ 148.9 (C aromatic), 141.8 (C aromatic), 131.3
(C aromatic), 115.6 (CH aromatic), 54.0 (d, J = 8 Hz, CH2), 29.3
(CH(CH3)2), 25.4 (CH(CH3)2), 24.1 (CH(CH3)2) (carbene carbon
= 0.0529, GOF = 1.068. CCDC-885582 contains supplementary
crystallographic data for this compound.
ASSOCIATED CONTENT
■
S
* Supporting Information
Figures giving selected 1H and 13C NMR spectra and a CIF file
giving crystallographic data for 7a. This material is available free
of charge via the Internet at http://pubs.acs.org.
not detected). IR: ν
̃
(cm−1) 2961, 2107 (N3), 1597, 1488, 1460, 1332,
1269. Anal. Found: C, 52.68; H, 6.02; N, 18.07. Calcd for
C27H36AgClN8: C, 52.65; H, 5.89; N, 18.19.
Synthesis of {N,N′-Bis[4-azido-2,6-diisopropylphenyl]-
imidazolin-2-ylidene}chlorocopper(I) (7b). 9b (100 mg, 0.163
mmol) was dissolved in 10 mL of degassed dichloromethane, copper(I)
chloride (47.9 mg, 0.49 mmol) was added, and the solution was stirred
for 1 h. The suspension that formed was filtered over Celite and
evaporated to afford a yellow powder. Yield: 89.5 mg (95%). 1H NMR
(400 MHz, DMSO-d6, ppm): δ 7.02 (s, 4H, CH aromatic), 4.06 (s; 4H,
CH2), 3.07 (hept, J = 7.0 Hz, 4H, CH(CH3)2), 1.31 (d, 12H, J = 7.0 Hz,
CH(CH3)2), 1.26 (d, 12H, J = 7.0 Hz, CH(CH3)2). 13C NMR (100
MHz, DMSO-d6, ppm): δ 201.3 (C carbene), 148.8 (C aromatic), 140.5
(C aromatic), 131.5 (C aromatic), 115.1 (CH aromatic), 53.6 (CH2),
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: Federico.cisnetti@univ-bpclermont.fr (F.C.); Arnaud.
gautier@univ-bpclermont.fr (A.G.).
Notes
The authors declare no competing financial interest.
REFERENCES
■
28.4 (CH(CH3)2), 24.8 (CH(CH3)2), 23.1 (CH(CH3)2). IR: ν
̃
(cm−1)
(1) (a) Díez−Gonzal
́
ez, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009,
2964, 2105 (N3), 1597, 1487, 1461, 1334, 1270. HRMS (ESI+):
calculated for C29H39CuN9 [M − (Cl + CH3CN)]+ 576.2625, found
576.2625. Anal. Found: C, 55.74; H, 6.28; N, 18.36. Calcd for
C27H36ClCuN8·0.25CH2Cl2: C, 55.21; H, 6.21; N, 18.90.
109, 3612. (b) Schuster, O.; Yang, L.; Raubenheimer, H. G.; Albrecht,
M. Chem. Rev. 2009, 109, 3445. (c) N-Heterocyclic Carbenes in Synthesis;
Nolan, S. P., Ed.; Wiley-VCH: Weinheim, Germany, 2006. (d) N-
Heterocyclic Carbenes From Laboratory Curiosities to Efficient Synthetic
́
́
Tools; Dıez-Gonzalez, S., Ed.; RSC Publishing: London, 2010.
Synthesis of {N,N′-Bis[2,6-diisopropyl-4-(4-hydroxymethyl-
1,2,3,1H-triazol-1-yl)phenyl]imidazol-2-ylidene}chlorocopper-
(I) (14a). 7a (200 mg, 0.338 mmol) was dissolved in 10 mL of 99/1
DMSO/water, and propargyl alcohol (100 μL, 1.75 mmol) was added.
The mixture was stirred at 50 °C for 16 h. The solvent was removed
under high vacuum, and the resulting solid was dissolved in 15 mL of
methanol and precipitated by dropwise addition of 40 mL of diethyl
ether to afford 14a as a pale yellow powder after filtration. This
procedure was repeated two times after concentration of the mother
liquor. Yield: 178.7 mg (75%). 1H NMR (400 MHz, DMSO-d6, ppm): δ
8.98 (s, 2H, CH triazole), 8.06 (s, 2H, CH imidazole), 7.96 (s, 4H, CH
aromatic), 5.40 (t, J = 5.5 Hz, 2H, OH), 4.66 (d, J = 5.5 Hz, 4H,
CH2OH), 2.54 (hept, J = 7.0 Hz, 4H, CH(CH3)2), 1.30 (m, 24H,
CH(CH3)2). 13C{1H} NMR (100 MHz, DMSO-d6, ppm): δ 178.5 (C
carbene), 149.4 (C aromatic), 147.7 (C aromatic), 138.2 (C aromatic),
133.9 (C aromatic), 124.7 (CH imidazole), 121.4 (CH triazole), 115.6
(CH aromatic), 55.1 (CH2OH), 28.8 (CH(CH3)2), 24.1 (CH(CH3)2),
(2) (a) Hindi, K. M.; Panzner, M. J.; Tessier, C. A.; Cannon, C. L.;
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̈
Complexes; Wiley: Chichester, U.K., 2010. (b) Shaughnessy, K. H. Chem.
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complex postfunctionalization see: (a) Gauthier, S.; Weisbach, N.;
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Klink, G. P. M.; van Koten, G. Organometallics 2009, 28, 4689.
̌
(c) Urankar, D.; Kosmrlj, J. Inorg. Chim. Acta 2010, 363, 3817.
(d) Warsink, S.; Drost, R. M.; Lutz, M.; Spek, A. L.; Elsevier, C. J.
Organometallics 2010, 29, 3109. (e) Yang, H.; Li, L.; Wan, L.; Zhou, Z.;
Yang, S. Inorg. Chem. Commun. 2010, 13, 1387. (f) Das, M. R.; Wang,
M.; Szunerits, S.; Gengembre, L.; Boukherroub, R. Chem. Commun.
2009, 2753. (g) Sun, Y.; Chen, Z.; Puodziukynaite, E.; Jenkins, D. M.;
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(h) Benson, M. C.; Ruther, R. E.; Gerken, J. B.; Rigsby, M. L.; Bishop,
L. M.; Tan, Y.; Stahl, S. S.; Hamers, R. J. ACS Appl. Mater. Interfaces
2011, 3, 3110. (i) Stengel, I.; Strassert, C. A.; Plummer, E. A.; Chien, C.-
23.0 (CH(CH3)2). IR: ν
̃
(cm−1) 3400 (broad, OH), 2964, 1601, 1478,
1329, 1223, 1021. Anal. Found: C, 57.30; H, 6.19; N, 15.41. Calcd for
C67H88Cl2Cu2N16O4·1/3dmso: C, 57.13; H, 6.27; N, 15.83.
Synthesis of {N,N′-Bis[2,6-diisopropyl-4-(4-hydroxymethyl-
1,2,3,1H-triazol-1-yl)phenyl]imidazolin-2-ylidene}-
chlorocopper(I) (14b). 7b (114 mg, 0.192 mmol) was dissolved in 6
mL of 99/1 DMSO/water, and propargyl alcohol (112 μL, 1.90 mmol)
was added. The mixture was heated to 50 °C for 15 h. The solvent was
removed under high vacuum, and the resulting solid was dissolved in 10
mL of methanol and crystallized by dropwise addition of 25 mL of
diethyl ether to afford a pale yellow powder after filtration. This
procedure was repeated two times after concentration of the mother
liquor. Yield: 96.3 mg (69%). 1H NMR (400 MHz, DMSO-d6, ppm): δ
8.93 (s, 2H, CH triazole), 7.88 (s, 4H, CH aromatic), 5.36 (t, J = 5.5 Hz,
2H, OH), 4.64 (d, J = 5.5 Hz, 4H, CH2OH), 4.17 (s, 4H, CH2), 3.18
(hept, 4H, J = 6.8 Hz, CH(CH3)2), 1.40 (d, J = 6.8 Hz, 12 H,
CH(CH3)2), 1.34 (d, J = 6.8 Hz, 12 H, CH(CH3)2). 13C NMR (100
MHz, DMSO-d6, ppm): δ 201.1 (C carbene), 149.0 (C aromatic), 137.5
(C aromatic), 134.3 (C aromatic), 121.3 (CH triazole), 115.8 (CH
aromatic), 55.0 (CH2OH), 53.6 (NCH2CH2N), 28.5 (CH(CH3)2),
H.; De Cola, L.; Bauerle, P. Eur. J. Inorg. Chem. 2012, 1795.
̈
(5) Warsink, S.; Drost, R. M.; Lutz, M.; Spek, A. L.; Elsevier, C. J.
Organometallics 2010, 29, 3109.
(6) Chardon, E.; Puleo, G. L.; Dahm, G.; Guichard, G.; Bellemin-
Laponnaz, S. Chem. Commun. 2011, 47, 5864.
(7) Rasmussen, L. K.; Boren, B. C.; Fokin, V. V. Org. Lett. 2007, 9,
5337.
(8) Gaulier, C.; Hospital, A.; Legeret, B.; Delmas, A. F.; Aucagne, V.;
Cisnetti, F.; Gautier, A. Chem. Commun. 2012, 48, 4005.
(9) Hospital, A.; Gibard, C.; Gaulier, C.; Nauton, L.; Thery, V.; El−
Ghozzi, M.; Avignant, D.; Cisnetti, F.; Gautier, A. Dalton Trans. 2012,
41, 6803.
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2004, 23, 1157.
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2009, 11, 1643.
24.8 (CH(CH3)2), 23.2 (CH(CH3)2) . IR: ν
̃
(cm−1) 3400 (broad, OH),
2963, 1601, 1479, 1333, 1250, 1021. Anal. Found: C, 56.54; H, 6.52; N,
15.73. Calcd for C33H44ClCuN8O2·0.5dmso: C, 56.50; H, 6.55; N,
15.50.
Crystal data for 9a: monoclinic, space group P21/n, a = 9.7500(4)
Å, b = 15.3223(7) Å, c = 22.0934(9) Å, β = 90.538(2)°, V = 3300.4(2)
Å3, Z = 4, Dcalcd = 1.146 g cm−3, final R (I > 3σ(I)) R1 = 0.0497 and wR2
(12) Andersen, J.; Madsen, U.; Bjorkling, F.; Liang, X. Synlett 2005,
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2209.
(13) Arduengo, A. J.; Krafczyk, R.; Schmutzler, R. Tetrahedron 1999,
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7907
dx.doi.org/10.1021/om3005355 | Organometallics 2012, 31, 7902−7908

Organometallics
Article
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(15) For control experiments, we prepared solutions analogous to
those used for functionalization reactions with propargyl alcohol
containing imidazolium salts 8a,b instead of the corresponding
copper(I) complexes. After 24 h at 50 °C <10% of 1,4-triazole products
were observed by 1H NMR with traces of another compound, possibly
the 1,5-regioisomer, and unreacted starting material as the main species.
(16) For mechanistic considerations in CuAAC see: (a) Bock, V. D.;
Hiemstra, H.; van Maarseveen, J. H. Eur. J. Org. Chem. 2005, 51.
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́
(c) For the mechanism of Cu(I)-NHCs, see: Dıez-Gonzal
́
ez, S.; Correa,
A.; Cavallo, L.; Nolan, S. P. Chem. Eur. J. 2006, 12, 7558.
́
(17) Dıez-Gonzal
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ez, S.; Stevens, E. D.; Nolan, S. P. Chem. Commun.
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́ ́ ́
Modrego, F. J.; Winterle, S.; Cunchillos, C.; Lahoz, F. J.; Oro, L. A.
Organometallics 2011, 30, 5493.
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in DMSO: Geary, W. J. Coord. Chem. Rev. 1971, 7, 81.
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University of Gottingen, Gottingen, Germany, 1997.
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(22) Betteridge, P. W.; Carruthers, J. R.; Cooper, R. I.; Prout, K.;
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(26) Dıez-Gonzal
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́
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7908
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