Imidazol(in)ium-2-carboxylates as efficient precursors to N-heterocyclic carbene complexes of copper and silver

Article abstract of DOI:10.1002/hc.21056

Copper and silver N-heterocyclic carbene (NHC) complexes were prepared through a simple, base-free protocol involving the decomposition of corresponding imidazol(in)ium-2-carboxylates under thermolytic conditions and a subsequent reaction of the in situ g

Full text of DOI:10.1002/hc.21056

Heteroatom Chemistry
Volume 23, Number 6, 2012
Imidazol(in)ium-2-Carboxylates as Efficient
Precursors to N-Heterocyclic Carbene
Complexes of Copper and Silver
Tomasz K. Olszewski and Dagmara E. Jasko´lska
Apeiron Synthesis, Klecin´ska 125, 54-413, Wroclaw, Poland
Received 23 May 2012; revised 19 August 2012
alkenes [4], Huisgen [3+2] cycloaddition [5], azirid-
ABSTRACT: Copper and silver N-heterocyclic car-
bene (NHC) complexes were prepared through a sim-
ple, base-free protocol involving the decomposition
of corresponding imidazol(in)ium-2-carboxylates un-
der thermolytic conditions and a subsequent reac-
tion of the in situ generated carbenes with cop-
per(I) or silver(I) chloride, respectively. The desired
NHC metal complexes were isolated with good yields
ination [6], cyclopropanation [7], methylenation [8],
and copper-catalyzed enantioselective transforma-
tions with high levels of selectivity [9]. In addition
to their many successful applications in catalysis,
NHC–copper complexes were also reported to ex-
hibit biological activity as antitumor agents [10].
The NHC copper species of type [CuCl(NHC)]
are not the only NHC complexes of interest in
group 11 of elements. Their silver analogues of type
[AgCl(NHC)] have also attracted significant interest
and nowadays are commonly used as NHC trans-
fer agents in transition metal chemistry [11] and
additionally have displayed interesting antimicro-
bial activity [12]. In light of the aforementioned
interesting catalytic and biological applications of
[CuCl(NHC)] and [AgCl(NHC)] complexes, facile
synthetic routes leading to high yields of those
compounds are highly desirable. In general, copper–
NHC complexes are prepared using either base-
mediated deprotonations [13], or via transmetala-
tion from the corresponding silver–NHC complexes
[14], or more recently by a reaction of copper(I) ox-
ide with imidazolium salts [15]. In turn, the syn-
thesis of silver–NHC complexes usually involves the
reaction of imidazolium salts with silver(I) oxide
[15b,16].
ꢀC
after simple crystallization.
2012 Wiley Periodi-
cals, Inc. Heteroatom Chem 23:605–609, 2012; View
this article online at wileyonlinelibrary.com. DOI
10.1002/hc.21056
INTRODUCTION
N-Heterocyclic carbene (NHC) complexes are estab-
lished as an important class of ligands for homo-
geneous catalysis, and their catalytic applications
are frequently reported [1]. The electronic and steric
modularity associated with the resulting complexes
has made the NHCs excellent candidates when de-
signing new metal complexes for catalysis. In that
respect, the syntheses of catalysts based on afford-
able metals are eagerly sought thus, making the NHC
copper species of type [CuCl(NHC)] of significant
importance. These complexes were already found
to be very effective in several catalytic transforma-
tions such as hydrosilylation of ketones [2], reduc-
tion of carbonyl compounds [3], hydroamination of
To the best of our knowledge, the application
of imidazol(in)ium-2-carboxylates as intermediates
for the synthesis of [CuCl(NHC)] and [AgCl(NHC)]
complexes is unknown [17]. For the application of
NHC-CO2 adducts as substrates in the synthesis of
NHC complexes with Rh, Ir, Ru, Pd, and Ti, see a
comprehensive review in [18]. Herein, we report on
Correspondence to: T. K. Olszewski; e-mail: tomasz.olszewski@
apeiron-synthesis.com.
ꢀC
2012 Wiley Periodicals, Inc.
605

606 Olszewski and Jasko´lska
SCHEME
1 Proposed synthesis of [CuCl(NHC)] and
[AgCl(NHC)] with the use of NHC-CO2 zwitterions.
efficient synthesis of [CuCl(NHC)] and [AgCl(NHC)]
complexes with the use of those useful intermedi-
ates. The presented simple and base-free protocol
involves decomposition of the imidazol(in)ium-2-
carboxylates under thermolytic conditions and a re-
action of the in situ generated carbenes with cop-
per(I) or silver(I) chloride, respectively.
SCHEME 2 Imidazol(in)ium-2-carboxylates used in this
study.
monly used NHCs, i.e., SIPr, IPr, SIMes, and IMes,
were used as substrates in the present study, and
their corresponding CO2 adducts were synthesized
(Scheme 2).
RESULTS AND DISCUSSION
NHC based on the imidazole ring upon a reaction
with carbon dioxide forms inner salts, which can be
stored and handled with no particular precautions
[19]. Such NHC-CO2 zwitterions readily lose their
CO2 moiety upon heating or dissolution; hence, they
act as convenient surrogates to air- and moisture-
sensitive free carbenes for organometallic synthe-
sis and organocatalytic applications [18]. We took
advantage of the liability of the NHC-CO2 zwit-
terions to generate active species in the prepara-
tion of [CuCl(NHC)] and [AgCl(NHC)] complexes
(Scheme 1). Four representative and most com-
Having in hand a palette of NHC-CO2 betaines,
we examined their application as substrates for the
synthesis of [CuCl(NHC)] complexes. Initially, the
preparation of the IPrCuCl complex using IPrCO2
betaine, as a model substrate, was investigated
(Table 1).
Knowing that the reactivity of the free carbene
with copper(I) chloride can be strongly modulated
by the reaction medium, we carried out the prelimi-
nary experiments in different solvents. Reaction run
with 1.2 equiv of CuCl in CHCl3 at 23◦C resulted
in formation of desired IPrCuCl product, albeit
TABLE 1 Synthesis of IPrCuCl from IPrCO2-–Screening of the Reaction Conditionsa
Entry
Reaction Condition
Result
1
2
3
4
CHCl3, 23◦C
CHCl3, 60◦C
Mixture of IPrCO2, IPrCuCl, and [(IPr)2Cu]+Cl−
Mixtureb of IPrCuCl and [(IPr)2Cu]+Cl−
Mixtureb of [(IPr)2Cu]+Cl− and IPrCuCl
IPrCuCl (90% yield)c
CH3CN, 80◦C
Toluene, 110◦C
aExperiments were carried out using 1.1 mmol (500 mg) of IPrCO2 and 1.2 equiv (1.32 mmol, 130 mg) of CuCl in 15 mL of appropriate solvent
for 12 h. Reactions were monitored by TLC. Products could be easily distinguished as the [(IPr)2Cu+]Cl− is much more polar than the IPrCuCl.
bEntry 2 mixture of IPrCuCl and [(IPr)2Cu]+Cl− in a ratio of 50:50; entry 3 mixture of IPrCuCl and [(IPr)2Cu]+Cl− in a ratio of 30:70.
cYield given for isolated product after recrystallization from the CH2Cl2/Et2O mixture.
Heteroatom Chemistry DOI 10.1002/hc

Imidazol(in)ium-2-Carboxylates as Efficient Precursors to N-Heterocyclic Carbene Complexes of Copper and Silver 607
TABLE 2 Synthesis of [CuCl(NHC)] and [AgCl(NHC)] Complexes from Zwitterionic Carboxylates-–Substrate Scopea
Entry
Substrate
Metal Source (MCl)
Product
Yield (%)b
1
2
3
4
5
6
7
8
IPrCO2
IMesCO2
SIPrCO2
SIMesCO2
IPrCO2
IMesCO2
SIPrCO2
SIMesCO2
CuCl
CuCl
CuCl
CuCl
AgCl
AgCl
AgCl
AgCl
IPrCuCl
IMesCuCl
SIPrCuCl
SIMesCuCl
IPrAgCl
IMesAgCl
SIPrAgCl
SIMesAgCl
90
88
85
80
95
92
82
88
aExperiments were carried out using 1.1 mmol of appropriate imidazol(in)ium-2-carboxylate and 1.2 equiv of CuCl or AgCl in 15 mL of toluene
at 110◦C for 12 h.
bYield given for isolated product after recrystallization from the CH2Cl2/Et2O mixture.
accompanied by its bis-complex [(IPr)2Cu+]Cl− and
a starting material IPrCO2 (Table 1, entry 1). In
turn, heating of the IPrCO2 with 1.2 equiv of CuCl
in CHCl3 at 60◦C resulted in total consumption of
IPrCO2 and yielded a mixture of both [(IPr)2Cu+]Cl−
and IPrCuCl complexes. Experiment run in CH3CN
again led to formation of a mixture of [(IPr)2Cu+]Cl−
and IPrCuCl; albeit, this time the latter was in the
minority (Table 1, entry 3). These results are in
agreement with the literature reports and show that
increasing the polarity of the solvent (dielectric con-
stant for CHCl3 = 4.2 and for CH3CN = 37.5) [20]
leads to an increase in the amount of the bis-NHC
carbene [21]. Finally, and to our satisfaction, a reac-
tion performed in toluene (dielectric constant = 2.3)
[20] at 110◦C furnished almost exclusively the de-
sired IPrCuCl complex with 90% yield (traces of the
[(IPr)2Cu+]Cl− were removed by recrystallization of
the crude from a mixture of CH2Cl2/Et2O) (Table 1,
entry 4).
Having the optimized reaction conditions in
hand, a selected spectrum of NHC-CO2 zwitterions
was examined to test the scope of the presented pro-
tocol (Table 2).
Different saturated and unsaturated imidazol
(in)ium-2-carboxylates were tolerated under the pre-
sented, optimized reaction conditions. Pure copper
complexes of type [CuCl(NHC)] were obtained in
good yields and high purity after simple recrystal-
lization from the CH2Cl2/Et2O mixture (Table 2 en-
tries 1–4). It has to be mentioned that the advantage
of the applied decarboxylation method is the absence
of a strong base, usually needed for the generation
of carbene. It is known that the presence of potas-
sium tert-butoxide in the synthesis of copper NHC
complexes is a source of undesired side products of
type Cu(NHC)(Ot-Bu) [5].
Subsequently, encouraged by the optimistic re-
sult obtained for the synthesis of [CuCl(NHC)] com-
plexes, we decided to further examine the syn-
thetic utility of imidazol(in)ium-2-carboxylates as
substrates in the preparation of silver complexes
of type [AgCl(NHC)]. For that purpose, we ap-
plied the above-mentioned optimized copper pro-
tocol using AgCl, instead of CuCl, as the silver
source (Table 2). The presented protocol worked well
for different saturated and unsaturated imidazol
(in)ium-2-carboxylates, and to our satisfaction pure
silver complexes of type [AgCl(NHC)] were easily ob-
tained and in good yields as well as with high purity
after simple recrystallization from the CH2Cl2/Et2O
mixture (Table 2 entries 5–8).
In
conclusion,
we
have
shown
readily
that
avail-
imidazol(in)ium-2-carboxylates,
able, isolable, air- and moisture-stable reagents,
offer an efficient route to NHC complexes of copper
and silver. By avoiding the strong base needed
in the free carbene route, our method minimizes
possible side reactions. The presented chemistry
provides an interesting and alternative synthetic
pathway to NHC copper and silver complexes of
type [CuCl(NHC)] and [AgCl(NHC)], respectively,
that have already found countless applications
in organocatalysis and organometallic chemistry
and additionally posses very interesting biological
activity.
Heteroatom Chemistry DOI 10.1002/hc

608 Olszewski and Jasko´lska
111, 2705; (b) Cabeza, J. A.; Garcia-Alvarez, P. Chem
Soc Rev 2011, 40, 5389; (c) John, A.; Ghosh, P.
Dalton Trans 2010, 39, 7183; (d) Nair, V.; Vellalath,
S.; Babu, B. P. Chem Soc Rev 2008, 37, 2691; (e) Peris,
E.; Crabtree, R. H. Coord Chem Rev 2004, 248, 2239;
(f) Herrmann, W. A. Angew Chem, Int Ed 2002, 41,
1290; (g) Viciu, M. S.; Germaneau, R. F.; Nolan, S.
P. Org Lett 2002, 4, 4053; (h) Bourissou, D.; Guerret,
O.; Gabbai, F. P.; Bertrand, G. Chem Rev 2000, 100,
39; (i) Herrmann, W. A.; Kocher, C. Angew Chem, Int
Ed 1997, 36, 2163.
EXPERIMENTAL
All imidazol(in)ium-2-carboxylates used in this
study were prepared according to the procedure de-
scribed earlier in the literature from appropriate
commercially available imidazol(in)ium chlorides,
potassium tert-butoxide (1 M solution in toluene),
and CO2 using toluene as a reaction solvent [19a].
Their structures were unambiguously confirmed by
standard spectroscopic techniques, and the obtained
data were in agreement with the literature reports:
IPrCO2 [19b], IMesCO2 [19b], SIPrCO2 [22], and
SIMesCO2 [22].
[2] (a) Diez-Gonzalez, S.; Stevens, E. D.; Scott, N. M.;
Petersen, J. L.; Nolan, S. P. Chem Eur J 2008, 14,
158; (b) D´ıez-Gonza´lez, S.; Scott, N. M.; Nolan, S. P.
Organometallics 2006, 25, 2355; (c) Diez-Gonzalez,
S.; Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P.
J Org Chem 2005, 70, 4784.
General Protocol for the Preparation of
[CuCl(NHC)] and [AgCl(NHC)] Complexes from
Imidazol(in)ium-2-carboxylates
[3] (a) Diez-Gonzalez, S.; Nolan, S. P. Acc Chem Res
2008, 41, 349; (b) Kaur, H.; Zinn, F. K.; Stevens, E.
D.; Nolan, S. P. Organometallics 2004, 23, 1157.
[4] (a) Munro-Leighton, C.; Delp, S. A.; Blue, E. D;
Gunnoe, T. B. Organometallics 2007, 26, 1483;
(b) Delp, S. A.; Munro-Leighton, C.; Goj, L. A.;
Ramirez, M. A.; Gunnoe, T. B.; Petersen, J. L.; Boyle,
P. D. Inorg Chem 2007, 46, 2365; (c) Munro-Leighton,
C.; Blue, E. D.; Gunnoe, T. B. J Am Chem Soc 2006,
128, 1446.
[5] Diez-Gonzalez, S.; Correa, A.; Cavallo, L.; Nolan, S.
P. Chem Eur J 2006, 12, 7558.
[6] (a) Liu, R.; Herron, S. R.; Fleming, S. A. J Org Chem
2007, 72, 5587; (b) Trost, B. M.; Dong, G. J Am Chem
Soc 2006, 128, 6054.
A 50-mL two-necked round-bottom flask equipped
with a magnetic stirring bar, a condenser, and a
three-way stopcock was charged with appropriate
imidazol(in)ium-2-carboxylate (1.1 mmol) and CuCl
or AgCl (1.32 mmol). The flask was purged with
argon prior to addition of degassed, dry toluene
(15 mL), and the resulting reaction mixture was
stirred at 110◦C for 12 h. Shorter reaction times re-
sulted in the formation of the desired NHC metal
complexes, albeit in lower yields. Experiments with
AgCl were carried out in the absence of light. After
that time, the reaction mixture was cooled down to
room temperature and filtered through a filter pa-
per. The filtrate was diluted with CH2Cl2 (25 mL)
and washed with H2O (2 × 15 mL). The organic
phase was dried over anhydrous MgSO4 and evapo-
rated to dryness under vacuum. The resulting crude
was dissolved in a little amount of CH2Cl2, and Et2O
was added to precipitate the product. The precipi-
tated [CuCl(NHC)] and [AgCl(NHC)] complexes as
white solids were collected by filtration and dried on
vacuum. The NMR spectra obtained for the isolated
complexes were consistent with the literature re-
ports: IPrCuCl [3b], IMesCuCl [15b], SIPrCuCl [23],
SIMesCuCl [2b], and IPrAgCl, IMesAgCl, SIPrAgCl,
and SIMesAgCl [15b],[21].
[7] Fructos, M. R.; Belderrain, T. R.; Nicasio, M. C.;
Nolan, S. P.; Kaur, H.; Diaz-Requejo, M. M.; Perez,
P. J. J Am Chem Soc 2004, 126, 10846.
[8] Lebel, H.; Davi, M.; Diez-Gonzalez, S.; Nolan, S. P. J
Org Chem 2007, 72, 144.
[9] (a) Brown, M. K.; May, T. L.; Baxter, C. A.; Hoveyda,
A. H. Angew. Chem. Int. Ed. 2007, 46, 1097; (b) Lee,
K. S.; Brown, M. K.; Hird, A. W.; Hoveyda, A. H.
J Am Chem Soc 2006, 128, 7182; (c) Martin, D.;
Kehrli, S.; d’Augustin, M.; Clavier, H.; Mauduit, M.;
Alexakis, A. J Am Chem Soc 2006, 128, 8416;
(d) Winn, C. L.; Guillen, F.; Pytkowicz, J.; Roland, S.;
Mangeney, P.; Alexakis, A. J Organomet Chem 2005,
690, 5672; (e) Van Veldhuizen, J. J.; Campbell, J. E.;
Giudici, R. E.; Hoveyda, A. H. J Am Chem Soc 2005,
127, 6877; (f) Tominaga, S.; Oi, Y.; Kato, T.; An,
D. K.; Okamoto, S. Tetrahedron Lett 2004, 45, 5585.
[10] (a) Teyssot, M. L.; Jarousse, A. S.; Chevry, A.; De
Haze, A.; Beaudoin, C.; Manin, M.; Nolan, S. P.; Diez-
Gonzalez, S.; Morel, L.; Gautier, A. Chem Eur J 2009,
15, 314; (b) Teyssot, M. L.; Jarousse, A. S.; Manin, M.;
Chevry, A.; Roche, S.; Norre, F.; Beaudoin, C.; Morel,
L.; Boyer, D.; Mahiou, R.; Gautier, A. Dalton Trans
2009, 6894.
ACKNOWLEDGMENT
Apeiron Synthesis acknowledges the Operation Pro-
gramme Innovative Economy (PO IG) for financial
support within the PO IG 1.4-4.1. Programme.
[11] For a recent example of silver–NHC complex as trans-
fer agent on Rh, Pd, and Au, see: Boronat, M.; Corma,
A.; Gonzalez-Arellano, C.; Iglesias, M.; Sanchez, F.
Organometallics 2010, 29, 134.
[12] Hindi, K. M.; Panzner, M. J.; Tessier, C. A.; Cannon,
C. L.; Youngs, W. J. Chem Rev 2009, 109, 3859.
[13] For application of Cu(I), see: (a) Michon, C.; Ellern,
A.; Angelici, R. J. Inorg. Chim. Acta 2006, 359, 4549;
(b) Schneider, N.; Cesar, V.; Bellemin-Laponnaz, S.;
REFERENCES
[1] (a) Benhamou, L.; Chardon, E.; Lavigne, G.;
Bellemin-Laponnaz, S.; Cesar, V. Chem Rev 2011,
Heteroatom Chemistry DOI 10.1002/hc

Imidazol(in)ium-2-Carboxylates as Efficient Precursors to N-Heterocyclic Carbene Complexes of Copper and Silver 609
Gade, L. H. J Organomet Chem 2005, 690, 5556;
(c) Mankad, N. P.; Gray, T. G.; Laitar, D. S.; Sadighi,
J. P. Organometallics 2004, 23, 1191. For appli-
cation of Cu(II), see; (d) Yun, J.; Kim, D.; Yun,
H. Chem Commun 2005, 5181; (e) Hu, X.; Castro-
Rodriguez, I.; Meyer, K. J Am Chem Soc 2003, 125,
12237.
Mas-Marza, E.; Poyatos, M.; Sanau, M.; Crabtree,
R. H.; Peris, E. Angew Chem, Int Ed 2005, 44, 444;
(e) Kascatan-Nebioglu, A.; Panzner, M. J.; Garrison,
J. C.; Tessier, C. A.; Youngs, W. J. Organometallics
2004, 23, 1928; (f) Lin, I. J. B.; Vasam, C. S. Com-
ments Inorg Chem 2004, 25, 75; (g) Quezada, C. A.;
Garrison, J. C.; Panzner, M. J.; Tessier, C. A.; Youngs,
W. J. Organometallics 2004, 23, 4846.
[14] (a) Winkelmann, O.; Nather, C.; Luning, U.
J
Organomet Chem 2008, 693, 923; (b) Wan, X.-J.; Xu,
F.-B.; Li, Q.-S.; Song, H.-B.; Zhang, Z.- Z. Inorg Chem
Commun 2005, 8, 1053; (c) Larsen, A. O.; Leu, W.; Ni-
eto Oberhuber, C.; Campbell, J. E.; Hoveyda, A. H. J
Am Chem Soc 2004, 126, 11130.
[17] Hahn, F. E.; Jahnke, M. C. Angew Chem, Int Ed 2008,
47, 3122.
[18] For a comprehensive review, see: Delaude, L. Eur J
Inorg Chem 2009, 1681.
[19] (a) Van Ausdall, B. R.; Glass, J. L.; Wiggins, K. M.;
Aarif, A. M.; Louie, J. J Org Chem 2009, 74, 7935; (b)
Duong, H. A.; Tekavec, T. N.; Arif, A. M.; Louie, J.
Chem Commun 2004, 112; (c) Kuhn, N.; Steimann,
M.; Weyers, G. Z Naturforsch, B 1999, 54, 427.
[20] Linde, D. R. Handbook of Chemistry and Physiscs,
85th ed.; CRC Press: Boca Raton, FL, 2004-2005; Sec-
tion 8, p. 141.
[21] Fremont P.; Scott M. N.; Stevens E. D.; Ramnial T.;
Lightbody O. C.; Macdonald C. L. B.; Clyburne J.
A. C.; Abernethy C. D.; Nolan S. P. Organometallics
2005, 24, 6301.
[22] Tudose, A.; Delaude, L.; Andre, B.; Demonceau, A.
Tetrahedron Lett. 2006, 48, 8529.
[23] Goj, L. A.; Blue, E. D.; Delp, S. A.; Gunnoe, T. B.;
Cundari, T. R.; Pierpont, A. W.; Petersen, J.; Boyle,
P. D. Inorg Chem 2006, 45, 9032.
[15] (a) Chun, J.; Lee, H. S.; Jung, I. G.; Lee, S. W.; Kim,
J. H.; Son, S. U. Organometallics 2010, 29, 1518;
(b) Citadelle, C. A.; Le Nouy, E.; Bisaro, F.; Slawin,
A. M. Z.; Cazin, C. S. J. Dalton Trans 2010, 39, 4489;
(c) Simonovic, S.; Whitwood, A. C.; Clegg, W.; Har-
rington, R. W.; Hursthouse, M. B.; Male, L.; Douth-
waite, R. E. Eur J Inorg Chem 2009, 1786; (d) Tulloch,
A. A. D.; Danopoulos, A. A.; Kleinhenz, S.; Light, M.
E.; Hursthouse, M. B.; Eastham, G. Organometallics
2001, 20, 2027.
[16] (a) Lin, J. C. Y.; Huang, R. T. W.; Lee, C. S.;
Bhattacharyya, A.; Hwang, W. S.; Lin, I. J. B. Chem
Rev 2009, 109, 3561; (b) Lee, C. S.; Pal, S.; Yang,
W. S.; Hwangi, W. S.; Lin, J. B. J Mol Catal, A:
Chem 2008, 280, 115; (c) Garrison, J. C.; Youngs,
W. J. Chem Rev 2005, 105, 3978; (d) Viciano, M.;
Heteroatom Chemistry DOI 10.1002/hc