Copper(I) thiophenolate in copper N-heterocyclic carbene preparation

Article abstract of DOI:10.1016/j.tetlet.2010.07.124

Copper(I) thiophenolate was considered as a copper source for the synthesis of Cu(I)-N-heterocyclic carbenes (Cu(I)-NHCs). It displayed a dual mode of reactivity allowing the synthesis of both thiophenolato-Cu(I)-NHCs via the free carbene in a one-pot procedure starting from imidazolium chlorides and chloro-Cu(I)-NHCs by a salt metathesis reaction starting from chloro-Ag(I)-NHCs.

Full text of DOI:10.1016/j.tetlet.2010.07.124

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Tetrahedron Letters 51 (2010) 5226–5229
Contents lists available at ScienceDirect
Tetrahedron Letters
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Copper(I) thiophenolate in copper N-heterocyclic carbene preparation
Federico Cisnetti a,b, Pascale Lemoine c, Malika El-Ghozzi d,e, Daniel Avignant d,e, Arnaud Gautier a,b,
*
a Clermont Université, Université Blaise Pascal, Laboratoire SEESIB, BP 10448, F-63000 Clermont-Ferrand, France
b CNRS, UMR 6504, SEESIB, F-63177 Aubiere, France
c Université Paris Descartes, Laboratoire de Cristallographie et RMN biologiques UMR 8015, Faculté de Pharmacie, 4 avenue de l’Observatoire, 75006 Paris, France
d Clermont Université, Université Blaise Pascal, Laboratoire des Matériaux Inorganiques, BP 10448, F-63000 Clermont-Ferrand, France
e CNRS, UMR 6002, LMI, F-63177 Aubiere, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Copper(I) thiophenolate was considered as a copper source for the synthesis of Cu(I)-N-heterocyclic carb-
enes (Cu(I)-NHCs). It displayed a dual mode of reactivity allowing the synthesis of both thiophenolato-
Cu(I)-NHCs via the free carbene in a one-pot procedure starting from imidazolium chlorides and
chloro-Cu(I)-NHCs by a salt metathesis reaction starting from chloro-Ag(I)-NHCs.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 11 May 2010
Revised 15 July 2010
Accepted 21 July 2010
Available online 30 July 2010
Keywords:
N-Heterocyclic carbenes
Transmetallation
Copper
Thiophenolate
Several methods are extensively used to generate metal-NHCs
(NHCs: N-heterocyclic carbenes).1 Besides the method reported
by Lappert based on Wanzlick equilibrium, synthetic routes can
be casted as follows: (i) the direct addition of free NHCs—isolated
or prepared in situ—onto a metal precursor,2 (ii) in situ deprotona-
tion of imidazol(in)ium salts by metal oxides3 (most frequently
Ag2O) that may be followed by (iii) carbene transfer4 (iv) tautomer-
ization of N-coordinated imidazoles5, and (v) addition of propar-
gylamine to isocyanide metal complexes6 (Scheme 1).
Among the above-mentioned routes, methods (i) and (ii) + (iii)
are probably the most widely used. The direct addition method—
most frequently performed with carbenes prepared in situ—nor-
mally requires that reactions are conducted with exclusion of O2,
H2O, and CO2. The carbene transfer method is usually performed
with silver NHCs as starting materials.4 A drawback of method
(iii)—particularly in the case of a transfer from a silver carbene—
is the possibility of a redox side reaction between Ag(I) and a spe-
cies containing the other metallic element. Indeed, several cop-
per(I) complexes have been reported to be oxidized by silver
triflate.7a,7b A similar redox reaction between Cu(I) and Ag(I) giving
copper(II) compounds and silver metal is probably one of the rea-
sons for the unsuccessful syntheses of some Cu(I)-NHCs using
method (iii). In addition, oxidation by Ag(I) as an undesired reac-
tion in carbene transfer with oxidizable metal centers (Ru(II),
Rh(I)) has been described.7c
During a program devoted to the synthesis of anticancer Cu(I)-
NHCs including chelating N-donor groups, we experienced unsuc-
cessful NHC transfer to copper(I) chloride (silver transfer method)
due presumably to metal-centered oxidation.8 To circumvolve this
problem, we hypothesized that copper(I) thiolates could replace
CuCl as thiolato-copper species that are hardly oxidizable. For this
purpose, we selected commercially available or easily prepared
polymeric copper(I) thiophenolate.9 However, by subjection of
[AgCl(NHC)] complexes to carbene transfer reactions with CuSPh,
we evidenced an unexpected conversion to [CuCl(NHC)] adducts
(Scheme 2A). The reaction implies thus formally a carbene transfer
R
N
R
N
(i)
+
M X
M X
N
R
N
R
+ MX
M'= Ag (iii)
R
R
(ii)
(iv)
(v)
N
N
Metal
oxide
H +
X
M' X
N
R
M
N
N
R
H
N
H
M X
[M]
N
R
N
R
R
N
RNC [M]
+
H2N
N
R
* Corresponding author. Tel.: +33 4 73 40 76 46; fax: +33 4 73 40 77 17.
E-mail address: arnaud.gautier@univ-bpclermont.fr (A. Gautier).
Scheme 1. General methods for the preparation of metal-NHCs.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.124

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5227
Table 2
R
N
R
N
Addition of in situ-prepared free NHC onto copper(I) thiophenolate
"
"
"
"
"
(A)
(B)
+
+
AgCl
S Cu
S Cu
+
CuCl
S Ag
N
R
N
R
R
N
R
N
"
"
(B)
R
N
R
N
+
S Cu
Cu SPh
"
N
R
N
R
Cu
S
N
R
N
R
Entry
NHC
[Cu(SPh)(NHC)]
Isolated yield (%)
Scheme 2. Copper(I) thiophenolate reactions described herein.
1
2
3
4
IMes
SIMes
IPr
[Cu(SPh)(IMes)]
[Cu(SPh)(SIMes)]
[Cu(SPh)(IPr)]
0a
0a
89
90
SIPr
[Cu(SPh)(SIPr)]
concomitant with an anion metathesis. A very recent literature re-
port mentions a similar reaction with copper(I) iodide.10 The reac-
tion outcome may be influenced by a favorable balance of the
solubilities of CuSPh and AgSPh and the strength of the thiolato
and NHC bonds to Ag and Cu (increased softness of Ag+ in compar-
ison with Cu+). Moreover, it could be argued that AgSPh possesses a
lesser oxidizing power than AgCl (from extrapolation of reference
data on the redox potential of AgnX, X = halides, sulphide, and
n = 1, 2).11 The application of this synthetic method to the selected
Cu(I)-NHCs is reported in this letter. In addition, we report that
CuSPh can be used efficiently in the direct addition of NHCs to form
[Cu(SPh)(NHC)] (Scheme 2B). The latter products have been re-
ported to have applications in the catalytic addition of S–H bonds
to electron-deficient olefins.12 CuSPh may thus be synthetically
useful in both routes A and B in Cu(I)-NHC synthesis.
a
Unstable products.
thiophenol. To the best of our knowledge, no report relates the
conceptually simpler addition of the free carbene directly onto
copper thiophenolate.15 The results of route B are compiled in Ta-
ble 2.
All attempts to isolate cleanly the copper(I)-NHCs containing
SIMes and IMes ligands failed, a feature reminiscent with Gunnoe’s
group report.16 On the other hand, the two more hindered carbenes
IPr and SIPr allow an easy synthesis in good yield.
We were interested in synthesizing [CuCl(IMesPic)] for its po-
tential biological activity.13e All attempts to synthesize this Cu(I)-
NHC by methods (i), (ii) (Cu2O), and (ii) + (iii) (Ag2O, then CuCl)
failed. Therefore, we used route A method. The starting silver(I)-
NHC (1) was easily obtained with the classical silver oxide route
starting from an imidazolium chloride as depicted in Scheme 3.
Complex 1 is of highly crystalline nature and suitable samples
for X-ray diffraction are straightforwardly obtained. Figure 1 de-
picts an ellipsoid plot of 1.17
To evaluate the potential of copper(I) thiophenolate in both
reactions we selected a range of usual NHCs—SIMes, IMes, SIPr,
and IPr—that we reacted by both route A (transfer from silver chlo-
ride-NHCs) and route B (reaction with a free carbene generated in
situ).13 The reactions were conducted under the following condi-
tions: (A) transmetallation in refluxing dichloromethane for 2 h
t
and (B) direct addition by generating the carbene with BuONa in
ꢀ
The silver NHC 1 crystallizes in the centrosymmetrical P21=n
dry THF in the presence of CuSPh. Results for route A are compiled
in Table 1. All the complexes reported in this table were already re-
ported in similar yields by direct addition of CuCl on the free car-
bene or by silver transfer (Scheme 1, route (i) or (ii) + (iii)).14
In all cases, inspection of the 1H NMR of the crude reaction mix-
tures (see Supplementary data) revealed a clean and total conver-
sion to the desired copper N-heterocyclic carbene core and only
trace impurities of thiophenol. Cu(NHC)2 species were detected
(0–15%) in the crude mixture as in the transfer protocol onto CuCl.
Analytically pure chloro-Cu(I)-NHCs were easily obtained after
recrystallization and structures were confirmed by comparison
with the literature data.
Metal-NHC thiolates have been reported previously by Gun-
noe’s group.12 Although the [Cu(SPh)(SIMes)] complex was not
described and [Cu(SPh)(IMes)] was reported to be unstable,
[Cu(SPh)(IPr)] and [Cu(SPh)(SIPr)] have been synthesized in good
yields by the acid–base reaction between [CuMe(NHC)] and
space group. The crystal structure of 1 highlights a symmetrical di-
meric structure bridged solely by two chlorides without participa-
tion of the picolyl moiety in the metal bonding. The carbon–silver
bond length falls into the usual range reported in the literature.18
This dimeric arrangement was already observed by Danopoulos
and co-workers in the bromide series.19 The crystal packing is sup-
ported by
p–p stacking interactions between aromatic moieties.
Structural features of interest are collected in Table 3.
Despite a number of variations of the experimental conditions
(introduction of an inert atmosphere, variation of solvents, and
temperature), the method (iii) from 1 onto CuCl invariably fails
to furnish cleanly the Cu(I) carbene and yields unidentified green-
ish solids, presumably containing Cu(II). For that reason, we were
pleased to observe a clean and efficient formation of compound 2
using our copper(I) thiophenolate transfer method (Scheme 4).
The transmetallation occurs in boiling dichloromethane and the
product is obtained after a simple filtration over Celite. Crystals
suitable for X-ray diffraction are obtained in 65% yield by a slow
diffusion of pentane vapors to a saturated solution of 2 in dichloro-
methane. X-ray diffraction highlights an almost symmetrical
Table 1
Synthesis of [CuCl(NHC)] using copper(I) thiophenolate
R
N
R
N
"
+
"
"
"
(A)
AgCl
S Cu
+
CuCl
S Ag
N
N
R
N
R
N
H, Cl
N
N
Ag2O, DCM
Cl
Cl
N
N
N
N
Ag
Ag
Entry
[AgCl(NHC)]
[CuCl(NHC)]
[CuCl(IMes)]
[CuCl(SIMes)]
[CuCl(IPr)]
Yielda (%)
N
1
2
3
4
[AgCl(IMes)]
[AgCl(SIMes)]
[AgCl(IPr)]
75
76
87
90
1
[AgCl(SIPr)]
[CuCl(SIPr)]
a
Refers to pure isolated product by crystallization.
Scheme 3. Synthesis of the starting silver(I) NHC 1.

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5228
F. Cisnetti et al. / Tetrahedron Letters 51 (2010) 5226–5229
Figure 1. Thermal ellipsoid plot (50% probability) of Ag(I)-NHC (1).
Table 3
Lengths, angles, and torsions of interest for complex 1
Lengths (Å)
C1–Ag
2.0762(19)
Ag–Cl
2.0763(19)
Angles (°)
Ag–Cl0
2.9916(6)
Agꢀ ꢀ ꢀAg0
3.7027(4)
Torsions (°)
Clꢀ ꢀ ꢀCl0
3.914
C1–Ag–Cl
166.81(5)
C1–Ag–Cl0
99.57(5)
C2–N1–C1–Ag
176.28(14)
C3–N2–C1–Ag
ꢁ175.86(14)
N
CuCl
+
Mes
N
Cl
Cl
N
Ag
Ag
Mes
N
N
Cl
N
Mes
N
"
+
"
N
Cu
S Cu
N
N
Cu
Cl
N
N
Mes
1
2
Scheme 4. Transmetallation using ‘Cu-SPh’ to obtain 2.
dimeric structure in which the picolyl moieties now participate to
the metal binding and bridge the copper(I) atoms (Fig. 2). In addi-
tion, the crystal lattice contains two molecules of dichloromethane.
Structural features of interest of 2, which crystallizes in the
Figure 2. Thermal ellipsoid plot (50% probability) of [Cu2Cl2(IMesPic)2]ꢀ2CH2Cl2 (2).
20
ꢀ
noncentrosymmetric P1 space group are collected in Table 4.
The complex displays a C–Cuꢀ ꢀ ꢀC–Cu core adopting a distorted dia-
mond shape. Each Cu atom is bound to the C1 NHC carbon, a pyr-
idine nitrogen and a chloride. The Cu–C bond falls in the normal
range.21 A similar dimeric structure with a weak copper–copper
interaction has been reported in the bromide series (synthesized
by the Cu2O route).22 In comparison with that structure, the pres-
ence of chloride instead of bromide as the Cu(I) ligand induces
some structural modifications—viz. the lengthening of the Cu–N
bond (+0.04 Å) and an interesting shortening of the Cu–Cu distance
(ꢁ0.08 Å).
In conclusion, we have reported that copper(I) thiophenolate
possesses a dual behavior by reacting with free N-heterocyclic
carbenes to form [Cu(SPh)(NHC)] or by participating in a transmet-
allation reaction followed by a salt metathesis to form [CuCl(NHC)]
even in the case of a complex unreachable by the usual transmet-
allation of a silver precursor. These methods add to the synthetic
arsenal employed to generate copper(I) NHCs that possess catalytic
and biological applications.

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F. Cisnetti et al. / Tetrahedron Letters 51 (2010) 5226–5229
5229
Table 4
Lengths, angles, and torsion of interest for complex 2
0
Lengths (ÅA)
Cu–C
1.945(5); 1.981(5)
Cu–N
2.060(5); 2.083(5)
Cu–Cu
2.5637(17)
Cu–Cl
2.3642(19); 2.336(2)
Cuꢀ ꢀ ꢀC
2.518(5); 2.606(5)
Angles (°)
Cl–Cu–Cu
134.02(4); 133.86(4)
C–Cu–N
N–Cu–Cu
122.90(12); 120.50(12)
C–Cu–Cl
C–Cu–Cu
65.83(15); 69.06(14)
N–Cu–Cl
95.64(13); 97.71(12)
Cu–Cꢀ ꢀ ꢀCu
68.29(14); 66.75(15)
130.08(19); 130.63(18)
109.40(15); 106.48(13)
Torsions (°)
Cl–Cu–Cu–Cl
179.6
N–Cu–Cu–N
179.6
N–Cu–Cu–Cl
38.1–38.5
13. (a) SIMes: 1,3-bis-(2,4,6-trimethylphenyl)imidazolin-2-ylidene.; (b) IMes: 1,3-
bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene.; (c) SIPr: 1,3-bis-(2,6-diisopro-
pylphenyl)imidazolin-2-ylidene.; (d) IPr: 1,3-bis-(2,6-diisopropylphenyl)imi-
dazol-2-ylidene.; (e) IMesPic: 1-(2,4,6-triphenylmethyl)-3-(2-picolyl)-imida-
zol-2-ylidene.
14. (a) Winkelmann, O.; Nather, C.; Luning, U. I. J. Organomet. Chem. 2008, 693,
923–932; (b) Seo, H.; Hirsch-Weil, D.; Abboud, K. A.; Hong, S. J. Org. Chem.
2008, 73, 1983–1986; (c) Park, K. H.; Ku, I.; Kim, H. J.; Son, S. U. Chem. Mater.
2008, 20, 1673–1675.
Supplementary data
Supplementary data (experimental procedures, compound
characterizations and selected NMR spectra) associated with this
article can be found, in the online version, at doi:10.1016/
j.tetlet.2010.07.124.
15. The synthesis of a bulky aromatic thiolate adduct of a Cu(I) NHC by a one-pot
procedure (free carbene + NaSAr + CuBr(SMe)2) was recently reported:
Groysman, S.; Holm, R. H. Inorg. Chem. 2009, 48, 621–627.
References and notes
16. [Cu(SPh)(IMes)] was reported in 75% yield by Gunnoe et al.12 as an unstable
product. The reported procedure relied on the direct precipitation of the
desired compound from the reaction medium (benzene). In our case, the
1. For general and historical references: (a) Crabtree, R. H.; Bourissou, D.; Guerret,
O.; Gabai, F. P.; Bertrand, G. Chem. Rev. 2000, 100, 39–92; (b) Herrmann, W. A.;
Kröcher, C. Angew. Chem., Int. Ed. 1997, 36, 2162–2187; (c) Wanzlick, H. W.;
Schikora, E. Angew. Chem. 1960, 72, 494–495; (d) Lappert, M. F. J. Organomet.
Chem. 1988, 358, 185–214.
product instability in CH2Cl2 precluded the isolation of [Cu(SPh)(IMes)].
ꢀ
17. Crystallographic data for 1:
C
18H19AgClN3, monoclinic, space group P21=n,
2. (a) Hahn, F. E.; Jahnke, M. C. Angew. Chem., Int. Ed. 2008, 47, 3122–3172; (b)
Díez-González, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3162–3676.
3. Silver oxide, see: (a) Wang, H. M. J.; Lin, I. J. B. Organometallics 1998, 17, 972–
975; Copper(I) oxide, see: (b) Arnold, P. L. Heteroat. Chem. 2002, 13, 534–539;
(c) Simonovic, S.; Whitwood, A. C.; Clegg, W.; Harrington, R. W.; Hursthouse, M.
B.; Male, L.; Douthwaite, R. E. Eur. J. Inorg. Chem. 2009, 1786–1795.
4. (a) See Ref. 3a.; (b) Lin, I. J. B.; Vasam, C. S. Coord. Chem. Rev. 2007, 251, 642–
670.
5. Sini, G.; Eisenstein, O.; Crabtree, R. H. Inorg. Chem. 2002, 41, 602–604.
6. (a) Ruiz, J.; Garcia, G.; Mosquera, M. E. G.; Perandones, B.; Gonzalo, M. P.;
Vivanco, M. J. Am. Chem. Soc. 2005, 127, 8584–8585; (b) Ruiz, J.; Perandones, B.;
Garcia, G.; Mosquera, M. E. G. Organometallics 2007, 26, 5687–5695.
7. Deliberate use of AgOTf as oxidant towards Cu(I)-NHCs (a) Hu, X.; Castro-
Rodriguez, I.; Meyer, K. J. Am. Chem. Soc. 2003, 125, 12237–12245; (b) Goj, L. A.;
Blue, E. D.; Delp, S. A.; Gunnoe, T. B.; Cundari, T. R.; Petersen, J. L.
Organometallics 2006, 25, 4097–4104; General review on Ag(I)-NHCs
reporting undesired redox side reactions: (c) Lin, I. J. B.; Vasam, C. S. Coord.
Chem. Rev. 2007, 251, 642–670 (and references therein).
colorless, a = 9.8230(8) Å, b = 16.6940(13) Å, c = 10.9792(8) Å, b = 94.503(2) Å,
V = 1794.9(2) Å3, T = 296(2) K, Z = 4, Final
R
(I > 2 (I)): R1 = 0.0285,
r
wR2 = 0.0684, GOF = 1.028. Structural information for 1 has been deposited
with CCDC as 771502, available free of charge from www.ccdc.cam.ac.uk/
conts/retreiving.html (or from the Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge, CB2 1EZ, UK (fax: +44-1223-336033).
18. For selected examples, see (a) de Frémont, P.; Scott, N. M.; Steven, E. D.;
Ramnial, T.; Lightbody, O. C.; Macdonald, C. L. B.; Clyburne, J. A. C.; Abernethy,
C. D.; Nolan, S. P. Organometallics 2005, 24, 6301–6309; (b) Ramnial, T.;
Abernethy, C. D.; Spicer, M. D.; McKenzie, I. D.; Gay, I. D.; Clyburne, J. A. C. Inorg.
Chem. 2003, 42, 1391–1393.
19. Tulloch, A. A. D.; Danopoulos, A. A.; Winston, S.; Kleinhenz, S.; Eastham, G. J.
Chem. Soc., Dalton Trans. 2000, 4499–4506.
20. The dinuclear complex unit is almost centrosymmetric but the lattice
symmetry is broken by the two CH2Cl2 present in the lattice. Crystal-
ꢀ
lographic data for 2: C38H42Cl6CuN6, triclinic, space group P1, a = 8.188(5) Å,
b = 10.933(5) Å, c = 11.360(5) Å,
a
= 85.088(5) Å, b = 85.235(5) Å,
c = 77.498(5)
Å, V = 987.0(9) Å3, T = 293(2) K, Z = 1, Final
R
(I > 2 (I)): R1 = 0.0388,
r
8. Teyssot, M. L.; Jarrousse, A. S.; Chevry, A.; De Haze, A.; Beaudoin, C.; Manin, M.;
Nolan, S. P.; Díez-González, S.;Morel, L.; Gautier, A. Chem. Eur. J. 2009, 15, 314–318.
9. We also synthetized ‘CuSPh’ according to Nguyen, L. M.;Dellinger,M. E.;Lee, J. T.;
Quinlan, R. A.; Rheingold, A. L.; Pike, R. D. Inorg. Chim. Acta 2005, 358, 1331–1336.
10. Badaj, A. C.; Dastgir, S.; Lough, A. J.; Lavoie, G. G. Dalton Trans. 2010, 39, 3361–
3365.
wR2 = 0.0979, GOF = 1.032. Structural information for 2 has been deposited
with CCDC as 771503.
21. (a) Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P. Organometallics 2004, 23,
1157–1160; (b) Díez-González, S.; Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S.
P. J. Org. Chem. 2005, 70, 4784–4796; (c) Díez-González, S.; Stevens, E. D.;
Nolan, S. P. Chem. Commun. 2008, 4747–4749; (d) Mankad, N. P.; Gray, T. G.;
Laitar, D. S.; Sadighi, J. P. Organometallics 2004, 23, 1191–1193.
22. Tulloch, A. A. D.; Danopoulos, A. A.; Winston, S.; Light, M. E.; Hursthouse, M. B.;
Eastham, G. Organometallics 2001, 20, 2027–2031.
11. Vany´sek, P. In CRC Handbook of Chemistry and Physics; Lide, R. D., Ed.; CRC Press:
Boca Raton, 2001; pp 8–21.
12. Delp, S. A.; Munro-Leighton, C.; Goj, L. A.; Ramírez, M. A.; Gunnoe, T. B.;
Petersen, J. L.; Boyle, P. D. Inorg. Chem. 2007, 46, 2365–2367.