Ruthenium catalysts bearing N-heterocyclic carbene ligands in atom transfer radical reactions

Article abstract of DOI:10.1016/S0040-4039(03)01477-1

The catalytic activity of ruthenium-p-cymene complexes bearing N-heterocyclic carbene ligands in atom transfer radical addition (ATRA) or polymerisation (ATRP) strongly depends on the substituents of the carbene ligand, thereby providing a nice illustration of the importance of organometallic engineering and ligand fine tuning in homogeneous catalysis.

Full text of DOI:10.1016/S0040-4039(03)01477-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6011–6015
Ruthenium catalysts bearing N-heterocyclic carbene ligands in
atom transfer radical reactions
Aurore Richel, Se´bastien Delfosse, Ce´dric Cremasco, Lionel Delaude, Albert Demonceau* and
Alfred F. Noels
Laboratory of Macromolecular Chemistry and Organic Catalysis, University of Lie`ge, Sart-Tilman (B.6a), B-4000 Lie`ge,
Belgium
Received 12 May 2003; accepted 14 June 2003
Abstract—The catalytic activity of ruthenium-p-cymene complexes bearing N-heterocyclic carbene ligands in atom transfer radical
addition (ATRA) or polymerisation (ATRP) strongly depends on the substituents of the carbene ligand, thereby providing a nice
illustration of the importance of organometallic engineering and ligand fine tuning in homogeneous catalysis.
© 2003 Elsevier Ltd. All rights reserved.
Atom transfer radical polymerisation (ATRP) is one of
the most versatile controlled radical polymerisation
techniques. Indeed, it allows to polymerise a wide vari-
ety of monomers, while offering excellent control of
both molecular weight and molecular weight distribu-
tion of the resulting polymers. ATRP is an extension of
the atom transfer radical addition (ATRA) also known
as the Kharasch addition. Both processes involve the
generation of active radicals from ‘dormant’ halo-
genated derivatives by a reversible redox process
catalysed by transition metal compounds (Scheme 1). If
the olefin is introduced in a proportion close to stoi-
chiometry compared to the halogen compound, forma-
tion of the single addition product is favoured and the
reaction is referred to as ATRA. In the presence of a
large excess of olefin compared to the haloalkane,
multiple insertion of the unsaturated monomer leads to
a macromolecular chain and the whole process is now
known as ATRP. The polymerisation is controlled by
maintaining a low concentration of active radical spe-
cies, thereby reducing the probability of termination
and establishing a fast dynamic equilibrium between
active and dormant species. Following the key observa-
tion by Sawamoto1 and Matyjaszewski2 that rutheniu-
m(II) and copper(I) complexes afford highly efficient
ATRP catalysts, a number of different metal ligand
combinations have been investigated.3
With the discovery of ATRP, the Kharasch addition of
polyhalogenated compounds across a CꢀC bond has
experienced a rejuvenation.4 Recently, we reported on
the exceptional efficiency of various ruthenium com-
plexes,5 including RuCl2(p-cymene)(PCy3).6,7 We also
Keywords: catalysis; olefins; radicals and radical reactions; ruthenium
and compounds.
* Corresponding author. Tel.: ++32/4 366 3495; fax: ++32/4 366 3497;
e-mail: A.Demonceau@ulg.ac.be
Scheme 1. Kharasch addition versus ATRP of methyl
methacrylate.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01477-1

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A. Richel et al. / Tetrahedron Letters 44 (2003) 6011–6015
(Table 1). Other substituent combinations on the imida-
zolylidene ring led to catalysts that were less efficient
and selective. It should be pointed out, however, that
stilbene formation did not contribute to more than 1 or
2% of the styrene consumption, indicative that ATRA
was strongly favoured over olefin metathesis under the
experimental conditions adopted yet (Scheme 2).
demonstrated that the Grubbs’ ruthenium benzylidene
complexes, RuCl2(=CHPh)(PR3)2, were efficient cata-
lyst precursors for both ATRP6,8 and Kharasch addi-
tion,8 and then expanded our investigations towards
N-heterocyclic carbene-containing ruthenium benzyli-
dene complexes.9
Nowadays, N-heterocyclic carbenes constitute
a
Thus, with styrene, subtle modifications of the R1 and
R2 substituents led to dramatic changes in the ability of
the corresponding ruthenium complexes to promote
efficient Kharasch additions. At first sight, electronic
effects seem to be more important than steric factors in
governing reactivity. For instance, the reactivity order
within the series of the N-mesityl-substituted NHC-
ruthenium complexes was (R2=) Cl (3)>H (2)>Me (1),
clearly demonstrating the beneficial influence of elec-
tron-withdrawing chloro substituents compared to the
electron-donating methyl groups. To further probe the
structure–activity relationship in operation within the
series of N-cyclohexyl-substituted ruthenium–NHC
complexes, we planned to prepare complex 6 with R2
chloro substituents for testing it in the Kharasch addi-
tion of CCl4 to styrene. However, our attempts to
synthesise the required free carbene ligand (R1=Cy,
R2=Cl) using the same experimental procedure12 that
afforded the NHC with R1=Mes and R2=Cl met with
failure.13
promising new class of ligands available for catalyst
engineering and fine tuning. They behave as phosphine
mimics, yet they are better s-donors and they form
stronger bonds to metal centres than most phosphi-
nes.10 In addition, their electronic and steric properties
are liable to ample modification simply by varying the
substituents on the nitrogen and the carbon atoms. We
have recently launched a detailed investigation on the
role of NHC ligands in ruthenium-p-cymene catalyst
precursors for the ring-opening metathesis polymerisa-
tion of cyclic olefins.11 We now report on the use of
new ruthenium catalysts bearing various NHC ligands
for the Kharasch addition of carbon tetrachloride to
olefins, and for the ATRP of vinyl monomers.
In a first set of experiments, the Kharasch addition of
CCl4 across the vinylic double bond of styrene was
investigated using the ruthenium complexes 1–5 as cata-
lysts. The reactions were carried out in toluene under
inert atmosphere. Carbon tetrachloride was introduced
in small excess compared to the olefin and the catalyst
loading was 0.3 mol%. Under these conditions, a quan-
titative conversion of styrene into (1,3,3,3-tetra-
chloropropyl)benzene was obtained in the presence of
complex 3 (R1=Mes, R2=Cl). Complex 5 bearing a
rather different carbene ligand (R1=Cy, R2=H) was
the second best choice and afforded the Kharasch
adduct in 62% yield after 24 h of reaction at 90°C
Scheme 2. Kharasch addition versus olefin metathesis of sty-
rene.
Table 1. Reaction of styrene with carbon tetrachloride catalysed by complexes 1–5a
Temperature
60°C
90°C
Complex
Conversion
(%)b
Kharasch addition Olefin metathesis
Conversion
(%)b
Kharasch addition
(%)b
Olefin metathesis
(%)b
(%)b
(%)b
1
2
3
4
5
1
11
95
10
22
m
7
89
1
m
2
3
m
0
47
70
100
38
27
48
97
8
0.5
1
1
m
0
11
88
62
a Reaction conditions: styrene (9 mmol), carbon tetrachloride (13 mmol), ruthenium complex (0.03 mmol), toluene (4 mL), dodecane (0.25 mL),
under nitrogen atmosphere. Reaction time, 24 h.
b Conversions and yields are based on styrene and determined by GC using dodecane as internal standard. m stands for minute amounts.

A. Richel et al. / Tetrahedron Letters 44 (2003) 6011–6015
6013
Under the same experimental conditions, at 90°C,
methyl methacrylate displayed a disappointingly low
reactivity, whichever NHC ligand was present on the
ruthenium centre (Table 2). Conversion remained below
20% and only minute amounts of the addition product
were detected by gas chromatography. Only when the
dicyclohexyl complexes 4 and 5 served as catalysts, was
the diadduct resulting from the insertion of two olefinic
units within the activated carbonꢁhalogen bond visible
in the chromatograms. In all cases higher oligomers
also formed and accounted for the mass balance, but
their high molecular weights prevented a satisfactory
GC analysis.
In order to get a better picture of the reaction course,
the Kharasch addition of carbon tetrachloride onto
styrene mediated by complexes 3 and 5 was monitored
by gas chromatography (GC) at regular time intervals.
The results are illustrated in Figure 1.
n-Butyl acrylate was more prone to undergo the atom
transfer radical addition of carbon tetrachloride than
MMA using the series of ruthenium–NHC complexes
under study. Indeed, complex 3 afforded a 99% conver-
sion and a 80% yield of the Kharasch adduct after 24 h
at 90°C. 1-Decene, on the other hand, was much less
reactive than styrene and n-butyl acrylate (Fig. 2). With
complex 3, some 60 h were needed to achieve the
complete conversion of the substrate. The desired
product (1,1,1,3-tetrachloroundecane) was obtained in
85% yield, together with a small amount (7% yield
based on 1-decene) of 9-octadecene (cis/trans=0.75)
resulting from olefin metathesis. In addition, isomerisa-
tion of 1-decene into internal olefins (mostly 2-decene)
also occurred and accounted for the mass balance.
Figure 1. Time dependence of styrene (ꢀ, ꢁ), Kharasch
adduct (ꢂ, ꢃ), and stilbenes (ꢄ, ꢅ) for reactions carried out
at 60 (ꢁ, ꢃ, ꢅ) and 90°C (ꢀ, ꢂ, ꢄ). Reaction conditions
are the same as in Table 1.
At 90°C, the difference of activity between the mesityl-
and cyclohexyl-substituted derivatives, although clearly
noticeable, was not striking (cf. Table 1). When the
temperature was decreased to 60°C, the substrate and
product evolution curves recorded with complex 3 were
inflected, but not markedly affected (Fig. 1, left).
Indeed, this catalyst still afforded a 95% styrene conver-
sion and a 89% yield of Kharasch adduct after 24 h.
The activity of complex 5, on the other hand, almost
completely collapsed when the reaction temperature
was lowered (Fig. 1, right). After 24 h at 60°C, the
conversion remained limited to 22%, and only half of
the monomer consumed led to the Kharasch reaction
(11% yield from styrene).
The close similarity of structure between complexes 1–5
and RuCl2(p-cymene)PCy3 prompted us to assess the
formers as possible catalysts for ATRP (Table 3). In a
series of preliminary experiments, methyl methacrylate
(MMA) and styrene (S) served as prototypical
monomers for screening the most efficient catalysts.
ATRP was initiated by carbon tetrachloride (2 equiv.
compared to the ruthenium complex) and conducted at
either 85°C (MMA) or 110°C (S).14
With MMA as the monomer (Table 3), complex 4 gave
the highest polymer yield (96%), but the polymerisation
was not controlled and the molecular weight distribu-
tion was very broad (Mw/Mn=2.5). Complex 3, on the
other hand, displayed a lower activity (44% yield of
PMMA) together with some level of control, as indi-
cated by the narrower polymer distribution (Mw/Mn=
1.4). As already observed with polyhalogenated
Table 2. Reaction of methyl methacrylate with carbon tetra-
chloride catalysed by complexes 1–5a
Complex
Conversion (%)a
Kharasch addition (%)a
Monoadduct
Diadduct
1
2
3
4
5
10
7
7
19
20
m
m
m
1.5
4
0
0
0
1
Figure 2. Time dependence of styrene ("), 1-decene (ꢃ),
n-butyl acrylate (ꢅ), methyl methacylate (ꢁ), and their
respective Kharasch adducts (2, ꢂ, ꢄ, ꢀ) for reactions
carried out at 90°C in the presence of complex 3. Reaction
conditions are the same as in Table 1.
1.5
a Experimental conditions are the same as in Table 1 (90°C, 24 h).

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A. Richel et al. / Tetrahedron Letters 44 (2003) 6011–6015
Table 3. Polymerisation of methyl methacrylate and styrene in the presence of carbon tetrachloride, catalysed by complexes
1–5a
Methyl methacrylate
Styrene
Mw/Mn
PMMA yield (%)b
Mn
Mw/Mn
PS yield (%)b
Mn
Stilbenes (%)b
c
c
c
c
Complex
1
2
3
4
5
10
76
44
96
51
33000
26000
6000
90000
53000
1.8
1.9
1.4
2.5
2.05
78
74
34
94
89
36000
28000
12000
30000
22000
1.85
1.85
1.25
1.7
3
4
46
m
m
1.5
a Reaction conditions: [MMA]0:[CCl4]0:[Ru]0=800:2:1; temperature, 85°C. [Styrene]0:[CCl4]0:[Ru]0=750:2:1; temperature, 110°C. Reaction time,
16 h.6,9
b Based on the monomer. m stands for minute amounts.
c Determined by size-exclusion chromatography (SEC) with PMMA and polystyrene calibration, respectively.
Figure 3. Experimental data for the polymerisation of styrene catalysed by ruthenium complex 3. (a) Time dependence of styrene
(ꢅ), polystyrene (ꢀ), and stilbenes (ꢂ). (b) Time dependence of ln([M]0/[M]t) where [M]0 and [M]t are the styrene concentrations
at times 0 and t.17 (c) Dependence of the PS molecular weight Mn on monomer conversion.17 (d) Dependence of the polydispersity
Mw/Mn on monomer conversion.17 Experimental conditions are the same as in Table 3.
initiators such as CCl4,5a,8,15 the molecular weight
(Mn=6000) was lower than the value calculated assum-
ing that one molecule of initiator generates one living
polymer chain, indicating that additional polymer
chains are generated through transfer reactions.16
obtained under ATRP conditions (375 equiv. of styrene
compared to CCl4: 46% yield of stilbenes) than under
ATRA conditions (0.69 equiv. of olefin compared to
CCl4: 1–3% yield of stilbenes). In light of these observa-
tions, a systematic investigation of the competitive reac-
tions of styrene (olefin metathesis, ATRA, and ATRP)
has been undertaken to allow for proper comparative
analysis. The results shown in Table 4 confirmed our
expectations. First, in the absence of carbon tetra-
chloride, complex 3 was an excellent catalyst precursor
for the metathesis of styrene. A 70% yield was achieved
at 90°C, with a turnover number of 210 after 10 h.
Second, in the presence of CCl4, styrene underwent
radical reactions in addition to olefin metathesis. In
accordance with our preliminary results, upon addition
of an increasing amount of CCl4, the metathesis activity
decreased significantly for the benefit of the Kharasch
addition. Thus, for 1.5 equiv. of CCl4 compared to
styrene, the ATRA went to 91% yield, whereas styrene
metathesis dropped to 6%.
Complex 3 also provided the highest level of control for
the polymerisation of styrene, with a polydispersity
Mw/Mn around 1.25 (Table 3). Noteworthy, with com-
plexes 1–3 bearing N-mesityl-substituted NHC ligands,
metathesis of styrene occurred competitively with poly-
merisation. trans-Stilbene and minute amounts of cis-
stilbene were formed in varying quantities according to
the substituents of the NHC ligand. With complex 3
(R1=Mes, R2=Cl), olefin metathesis was predominant
(49% yield based on styrene, after 25 h of reaction (Fig.
3a)), whereas with the parent N-mesityl-substituted
derivatives 1 (R2=Me) and 2 (R2=H) stilbene forma-
tion reached only 3–4%. Interestingly, complexes 4 and
5 bearing N-cyclohexyl-substituted NHC ligands were
devoid of any significant activity for the metathesis of
styrene.
Finally, the ability of complex 3 to control the poly-
merisation of styrene was investigated.17 The semiloga-
rithmic plot of ln([M]0/[M]t) versus time was linear
(Fig. 3b: y=−4.6298×10−3+5.8793×10−2 x; r2=0.996)
with a pseudo-first order rate constant (kapp) of 1.63×
10−5 s−1, indicating that the radical concentration
remained constant throughout the polymerisation run.
In addition, the molecular weights Mn increased lin-
From the results shown in Tables 1 and 3, it also
appeared that carbon tetrachloride had a detrimental
effect on olefin metathesis. Indeed, a rough comparison
of the ability of complex 3 to promote the metathesis of
styrene revealed that, despite the experimental condi-
tions were quite different, higher yields of stilbenes were

A. Richel et al. / Tetrahedron Letters 44 (2003) 6011–6015
6015
Table 4. Competitive reactions of styrene in the presence of carbon tetrachloride, catalysed by complex 3a
Carbon tetrachloride
None
0.01b
0.1b
0.5b
1.5b
Styrene conversion (%)c
Stilbenes (%)c
71
70
–
68
58
0
49
27
6
78
10
40
28
99
6
91
2
Kharasch adduct (%)c
(Oligo-) polystyrene (%)
0
10
16
a Reaction conditions: styrene (9 mmol), ruthenium complex (0.03 mmol), toluene (7.5 mL), dodecane (0.25 mL), under nitrogen atmosphere.
Temperature, 90°C. Reaction time, 10 h.
b Addition of CCl4 (equiv. of CCl4 compared to styrene).
c Conversions and yields are based on styrene, and determined by GC using dodecane as internal standard.
early with conversion (Fig. 3c: y=−572+378.71 x; r2=
0.980), thus demonstrating good control over Mn. Poly-
dispersities (Mw/Mn) were quite low (typically ca. 1.25)
and decreased with monomer conversion (Fig. 3d). By
contrast, the other ruthenium complexes tested led to
poorly controlled or uncontrolled polymerisations of
styrene.
6071–6074; (c) Simal, F.; Wlodarczak, L.; Demonceau,
A.; Noels, A. F. Eur. J. Org. Chem. 2001, 2689–2695.
6. Simal, F.; Demonceau, A.; Noels, A. F. Angew. Chem.
1999, 111, 559–562; Angew. Chem. Int. Ed. 1999, 38,
538–540.
7. (a) Simal, F.; Delaude, L.; Jan, D.; Demonceau, A.;
Noels, A. F. Polym. Prepr. (Am. Chem. Soc., Div. Polym.
Chem.) 1999, 40, 336–337; (b) Simal, F.; Jan, D.; Demon-
ceau, A.; Noels, A. F. In Controlled/Living Radical Poly-
merization: Progress in ATRP, NMP, and RAFT, ACS
Symposium Series 768, Matyjaszewski, K., Ed.; American
Chemical Society: Washington, DC 2000; pp. 223–233;
(c) Simal, F.; Sebille, S.; Hallet, L.; Demonceau, A.;
Noels, A. F. Macromol. Symp. 2000, 161, 73–85; (d)
Simal, F.; Jan, D.; Delaude, L.; Demonceau, A.; Spirlet,
M.-R.; Noels, A. F. Can. J. Chem. 2001, 79, 529–535.
8. Simal, F.; Demonceau, A.; Noels, A. F. Tetrahedron Lett.
1999, 40, 5689–5693.
To conclude, it should be pointed out that neither the
yields, nor the R1–R2 substituent combinations within
the NHC ligand were optimised. Thus, room for
improvement certainly exists. Nevertheless, this study
provides a glimpse of the synthetic possibilities arising
from the use of ruthenium N-heterocyclic carbene com-
plexes in radical reactions, and illustrates how the fine
tuning of the steric and electronic parameters of this
class of ruthenium complexes affects their catalytic
activity. Further work in this field is in progress.
9. Simal, F.; Delfosse, S.; Demonceau, A.; Noels, A. F.;
Denk, K.; Kohl, F. J.; Weskamp, T.; Herrmann, W. A.
Chem. Eur. J. 2002, 8, 3047–3052.
Acknowledgements
10. Bourissou, D.; Guerret, O.; Gabba¨ı, F. P.; Bertrand, G.
Chem. Rev. 2000, 100, 39–91.
11. (a) Delaude, L.; Demonceau, A.; Noels, A. F. Chem.
Commun. 2001, 986–987; (b) Delaude, L.; Szypa, M.;
Demonceau, A.; Noels, A. F. Adv. Synth. Catal. 2002,
344, 749–756.
12. Arduengo, A. J., III; Davidson, F.; Dias, H. V. R.;
Goerlich, J. R.; Khasnis, D.; Marshall, W. J.; Prakasha,
T. K. J. Am. Chem. Soc. 1997, 119, 12742–12749.
13. Preliminary investigations showed that the reaction of
1,3-dicyclohexylimidazol-2-ylidene with 2 equiv. of CCl4
This work has been carried out in the framework of the
TMR-HPRN CT 2000-10 ‘Polycat’ program of the
European Union. We are grateful to the ‘Fonds
National de la Recherche Scientifique’ (F.N.R.S.),
Brussels, for the purchase of major instrumentation,
and to the ‘Re´gion wallonne’ (Programme FIRST
Europe) for a fellowship to A.R.
References
in THF afforded
a mixture of 1,3-dicyclohexyl-2-
chloroimidazolium chloride and another yet unidentified
product instead of the expected 4,5-dichloro-1,3-dicyclo-
hexylimidazol-2-ylidene.
1. Kato, M.; Kamigaito, M.; Sawamoto, M.; Higashimura,
T. Macromolecules 1995, 28, 1721–1723.
2. Wang, J.-S.; Matyjaszewski, K. J. Am. Chem. Soc. 1995,
117, 5614–5615.
3. (a) Matyjaszewski, K.; Xia, J. Chem. Rev. 2001, 101,
2921–2990; (b) Kamigaito, M.; Ando, T.; Sawamoto, M.
Chem. Rev. 2001, 101, 3689–3745.
4. (a) Gossage, R. A.; van de Kuil, L. A.; van Koten, G.
Acc. Chem. Res. 1998, 31, 423–431; (b) Simal, F.;
Demonceau, A.; Noels, A. F. Recent Res. Devel. Org.
Chem. 1999, 3, 455–464; (c) Clark, A. J. Chem. Soc. Rev.
2002, 31, 1–11.
14. For polymerisation of methyl methacrylate and styrene
initiated by ethyl 2-bromo-2-methyl propionate and (1-
bromoethyl)benzene, respectively, see: Delaude, L.;
Delfosse, S.; Richel, A.; Demonceau, A.; Noels, A. F.
Chem. Commun. 2003, 1526–1527.
15. Ando, T.; Kamigaito, M.; Sawamoto, M. Tetrahedron
1997, 53, 15445–15457.
16. Destarac, M.; Matyjaszewski, K.; Boutevin, B. Macro-
mol. Chem. Phys. 2000, 201, 265–272.
17. In these data processings, both initial styrene concentra-
tions [M]0 and styrene conversions were corrected to
exclude the fraction of substrate converted into stilbenes
through the metathesis process.
5. (a) Simal, F.; Sebille, S.; Demonceau, A.; Noels, A. F.;
Nu´n˜ez, R.; Abad, M.; Teixidor, F.; Vin˜as, C. Tetrahedron
Lett. 2000, 41, 5347–5351; (b) Simal, F.; Wlodarczak, L.;
Demonceau, A.; Noels, A. F. Tetrahedron Lett. 2000, 41,