Mixed N-heterocyclic carbene/phosphite ruthenium complexes: Towards a new generation of olefin metathesis catalysts

Article abstract of DOI:10.1039/c0cc02448a

The synthesis, characterisation and catalytic behaviour of ruthenium indenylidene complexes bearing an N-heterocyclic carbene and triisopropylphosphite are described.

Full text of DOI:10.1039/c0cc02448a

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Mixed N-heterocyclic carbene/phosphite ruthenium complexes: towards a
new generation of olefin metathesis catalystsw
Xavier Bantreil, Thibault E. Schmid, Rebecca A. M. Randall, Alexandra M. Z. Slawin and
Catherine S. J. Cazin*
Received 8th July 2010, Accepted 11th August 2010
DOI: 10.1039/c0cc02448a
The synthesis, characterisation and catalytic behaviour of ruthenium
indenylidene complexes bearing an N-heterocyclic carbene and
triisopropylphosphite are described.
Since the last decade, olefin metathesis has become one of the
most useful tools in organic chemistry.1,2 Since the initial reports
of ruthenium alkylidene complexes for olefin metathesis,3 the
development of longer-living and more active pre-catalysts has
been the focus of numerous studies. One of the main break-
throughs in the area was the replacement of a phosphine ligand
by a N-heterocyclic carbene (NHC), increasing the reactivity
and stability of the corresponding complex (G-II, Fig. 1).4
Additional modifications afforded boomerang-type catalysts,
the most well-known being Hov-II.5 More recently, replacing
the benzylidene by an indenylidene has led to more stable
pre-catalysts (Ind-II).6,7 However, G-II and Ind-II find their
limitations in catalysis involving challenging substrates, where
the former does not tolerate harsh conditions and the latter
requires 2 to 5 mol% of catalyst to perform reactions
effectively.
Scheme 1 Synthesis of Ru-P(OR)3 complexes in CH2Cl2.
31P{1H} NMR experiments of the crude showed the formation
of two new complexes, in a ca. 9 : 1 ratio, with dP in CD2Cl2 of
113.8 and 122.0 ppm, respectively. Interestingly, when this
mixture was heated (toluene-d8, 80 1C, 1 h), the major product
is converted into the minor one. 1H and 13C{1H} NMR
analyses established that the reaction of Ind-III with P(OiPr)3
leads to complex Caz-1 as a mixture of two isomers: the
first, trans-Caz-1, features a trans configuration between the
NHC and the phosphite and is the kinetic product, while cis-
Caz-1—NHC and P(OiPr)3 in a mutually cis arrangement—is
the thermodynamic product (Scheme 1).
The most diagnostic feature is found in the 13C{1H} NMR
spectra of the two complexes by determination of the coupling
constants between the carbenic carbon and phosphorus atoms.
In this context, as no extensive experimental work involving
ligands other than phosphines and NHCs has yet been disclosed,
we chose to investigate the potential of inexpensive phosphites
as ligands in olefin metathesis pre-catalysts.8 Indeed, a synergistic
effect between the strong s-donor NHCs and strong p-acidic
phosphites on metals has already been reported, leading to
extremely long-living pre-catalysts in Pd coupling reactions.9
Herein, we report the synthesis, characterisation and catalytic
studies of a new ruthenium metathesis catalyst bearing a mixed
NHC/P(OR)3 ligand system.
2
Indeed, for trans-Caz-1, JCꢀP was found to be 127.8 Hz
(dC 217.3 ppm) whilst the cis-isomer (dC 208.95 ppm) displayed
2
2
a JCꢀP of 13.4 Hz, consistent with a trans and a cis JCꢀP
,
1
respectively. Additionally, H NMR spectral data show that,
for the trans isomer, the NHC is static and the P(OiPr)3 ligand
rotates freely. In contrast, the rotation of the phosphite ligand
in the cis complex is completely impeded due to the higher
steric constraint associated with this configuration. These
spectra exhibit a significant downfield shift of the indenylidene
proton H7 from trans-Caz-1 (8.32 ppm) to cis-Caz-1 (8.87 ppm).11
Finally, the structure of cis-Caz-1 was unambiguously con-
firmed by X-ray diffraction on single crystals (Fig. 2).
Commercially available 3rd generation ruthenium indenylidene
Ind-III,10 featuring the NHC ligand N,N0-bis[2,4,6-(trimethyl)-
phenyl]imidazolin-2-ylidene (SIMes), was reacted at room
temperature with one equivalent of triisopropylphosphite.
Fig. 1 Commercially available ruthenium-metathesis catalysts.
EaStCHEM School of Chemistry, University of St Andrews,
St Andrews, UK KY16 9ST. E-mail: cc111@st-andrews.ac.uk;
Fax: +44 (0)1334 463808
w Electronic supplementary information (ESI) available: Experimental
details and characterisation of complexes and metathesis products.
CCDC 776706 (cis-Caz-1). For ESI and crystallographic data in CIF
or other electronic format see DOI: 10.1039/c0cc02448a
Fig. 2 Graphical representation of cis-Caz-1. Selected bond distances
(A) and angles (1) (esd): Ru(1)–C(24) 1.881(8), Ru(1)–C(1) 2.067(7),
Ru(1)–P(1) 2.249(2), C(24)–Ru(1)–C(1) 98.7(3), C(24)–Ru(1)–P(1)
90.5(2), C(1)–Ru(1)–P(1) 100.06(19).
c
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 7115–7117 7115

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Table 1 Behaviour of trans-Caz-1 vs. cis-Caz-1a
Caz-1
Conv.b
Entry Substrate
1
Product
(mol%) T/1C t/h (%)
trans (1) 25
5
18
88
0
24
24
0.5
0.5
cis (1)
25
40c
60c
80c
0
4
0.5 499 (97)
2
trans (1) 25
5
24
80
0
cis (1)
25
80
0.5 499 (99)
3
trans (1) 25
24
24
52
0
Fig. 3 trans–cis isomerisation of Caz-1 (30–60 1C, CD3NO2).
cis (1)
25
80
0.5 499 (75)
8
cis-Caz-1 presents a slightly distorted square-pyramidal
geometry featuring the phosphite ligand in a cis position to
the NHC (C(1)–Ru(1)–P(1) = 100.061 (19)).12 cis-Caz-1 is a
rare example of a Ru-metathesis complex adopting a cis
configuration while solely bearing monodendate ligands.13ꢀ15
Futhermore, this represents, to the best of our knowledge, the
first example of an indenylidene-type complex displaying such
a configuration. On the other hand, this geometry has been
recently found in a limited number of Hoveyda-type catalysts,
the metal centre bearing then a bidentate ligand.15
4d
trans (2) 25
65
cis (2)
cis (2)
25
80
8
0
0.5 90
1.75 97 (81)
a
Reaction conditions: substrate (0.25 mmol), pre-catalyst (1 to 2 mol%),
solvent (0.1 M, CH2Cl2 or toluene for reactions, respectively, at room
b
temperature or 80 1C). Average of 2 runs; conversions were deter-
mined by 1H NMR based on substrates; selected isolated yields in
c
d
brackets. Toluene was used as solvent. 10: E/Z ratio 4 20/1.
In order to obtain information on this rare fluxional behaviour
displayed by Caz-1, kinetic NMR studies were carried out at
different temperatures (30–60 1C). The use of a polar solvent
was necessary in order to reach complete conversion to the
cis-isomer (Fig. 3). The Eyring plot obtained from these data
allowed the determination of thermodynamic parameters
associated with the isomerisation of trans-Caz-1. These
were found to be DHa = 22.6 kcal molꢀ1 and DSa
=
ꢀ4.2 cal molꢀ1 Kꢀ1 16
.
The low value of DS suggests that no
dissociation of the phosphite ligand occurs during the isomeri-
sation process. The assumption of a non-dissociative mechanism
was confirmed by an additional NMR experiment which
showed that the presence of an excess of free phosphite to
trans-Caz-1 in CD3NO2 (at 40 1C) had no influence on the rate
of isomerisation.16
Fig. 4 Comparison Caz-1 vs. state-of-the-art systems. Reaction condi-
tions: 11 (0.5 mmol), pre-catalyst (0.5 mol%), toluene (0.1 M, 5 mL).18
In order to observe a significant difference between catalyst
activities, a low catalyst loading of 0.5 mol% Ru (typical
loading used for such a reaction is 42 mol%) was employed in
this reaction. The kinetic profiling of these experiments are
presented in Fig. 4.18
Next, the catalytic activity of these new complexes was
evaluated in ring closing metathesis (RCM) of dienes and
enynes, and in cross-metathesis (CM) reactions. Our attention
first focused on the comparison of the catalytic behaviour
between the trans17 and cis isomers. The RCM of diallyltosyl-
amine 2 was first examined. Whilst trans-Caz-1 was able to
promote this transformation at room temperature (albeit with
lower activities compared to previously reported indenylidene
ruthenium complexes),7 its cis-analogue required heating
(Table 1, entry 1) and at 80 1C a rapid complete conversion
to the desired product 3, in the presence of cis-Caz-1, was
obtained. This same behaviour was observed in the ring
closing metathesis of diallylic malonate 4 and of enyne 6,
as well as in the cross-metathesis of alkene 8 with methyl
acrylate 9 (Table 1, entries 2–4), trans-Caz-1 is active at room
temperature while its cis counterpart requires thermal activa-
tion. Such reactivity indicates a latent character of the catalyst
system.
The pyridine-containing Ind-III did not show any activity
whilst second-generation pre-catalysts Ind-II, G-II and Hov-II
exhibited a fast initiation and high activity during the first
30 minutes. However, G-II rapidly decomposed (10 min) and
provided a poor conversion (16%), and Ind-II and Hov-II
could not achieve more than 60% conversion. In contrast, the
phosphite-containing Caz-1 system was able to promote this
reaction to complete conversion. Indeed, both trans and cis
pre-catalysts were found to be superior in longevity among all
catalysts tested and were able to reach complete conversion of
11 in less than 7 hours. This drastic improvement of the
longevity of the system bearing the phosphite ligand is in line
with observations made on Pd systems bearing mixed PCy3/
P(OR)3 ligand systems, where the P(OR)3 ligand was pre-
sumed responsible for this effect.9a,b In addition, the latent
behaviour of cis-Caz-1 compared to its trans isomer was again
observed as a thermal treatment of approximately 20 minutes
at 80 1C was necessary to activate cis-Caz-1. On the other
hand, passed this induction period of ca. 20 min, both isomers
trans- and cis-Caz-1 were then compared to commercially
available state-of-the-art pre-catalysts in the ring closing
metathesis of challenging tosylamine derivative 11.
c
7116 Chem. Commun., 2010, 46, 7115–7117
This journal is The Royal Society of Chemistry 2010

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The authors gratefully acknowledge the EC for funding this
project (FP7 grant CP-FP 211468-2 EUMET).
Notes and references
1 (a) R. H. Grubbs, in Handbook of Metathesis, Wiley-VCH,
Weinheim, 2003, vol. 1–3; (b) D. Astruc, New J. Chem., 2005, 29,
42; (c) P. H. Deshmukh and S. Blechert, Dalton Trans., 2007,
2479.
2 (a) A. H. Hoveyda and A. R. Zhugralin, Nature, 2007, 450, 243;
(b) S. Kotha and K. Lahiri, Synlett, 2007, 2767; (c) P. Compain,
Adv. Synth. Catal., 2007, 349, 1829.
3 (a) S. T. Nguyen, L. K. Johnson, R. H. Grubbs and J. W. Ziller,
J. Am. Chem. Soc., 1992, 114, 3974; (b) P. Schwab, M. B. France,
J. W. Ziller and R. H. Grubbs, Angew. Chem., Int. Ed. Engl., 1995,
34, 2039.
Scheme 2 Low catalyst loading experiments. Reaction conditions:
substrate (0.25 mol%), cis-Caz-1 (0.1–0.02 mol%), neat 120 1C for
14, 5, and 16 or toluene (0.5 M) at reflux for 3, 12 and 13, 8–24 h;
isolated yields, average of 2 runs.
4 (a) C. Samojlowicz, M. Bieniek and K. Grela, Chem. Rev., 2009,
109, 3708; (b) G. C. Vougioukalakis and R. H. Grubbs, Chem.
Rev., 2010, 110, 1746.
5 S. B. Garber, J. S. Kingsbury, B. L. Gray and A. H. Hoveyda,
J. Am. Chem. Soc., 2000, 122, 8168.
display nearly identical rates of reaction, suggesting that an
identical active species is present using either catalysts.
In order to test the reactivity limits of the phosphite system
and to demonstrate its true potential, low catalyst loading
experiments were conducted on RCM reactions of 2 using
several solvents with high boiling points.16 As no solvent led to
better conversion than toluene, even at temperatures above
110 1C, the catalytic performance of cis-Caz-1 was further
investigated either in this solvent or neat for various RCM
substrates (Scheme 2). As a general trend, a lower catalyst
loading was necessary to perform the RCM of tosylamine
derivatives compared to malonate dienes. The RCM of tosyl-
amine 2 was achieved with a high isolated yield of 3 (84%) at a
catalyst loading of 0.02 mol%. For the malonate analogue 14,
as well as for the 6-membered derivative 15, a catalyst loading
of 0.05 mol% allowed complete conversion and high isolated
yields. The slightly hindered tri-substituted olefin 5 was
obtained in a quantitative yield, using a catalyst loading of
0.075 mol%.
6 (a) V. Dragutan, I. Dragutan and F. Verpoort, Platinum Met. Rev.,
2005, 49, 33; (b) F. Boeda, H. Clavier and S. P. Nolan, Chem.
Commun., 2008, 2726; (c) H. Clavier, J. L. Petersen and
S. P. Nolan, J. Organomet. Chem., 2006, 691, 5444 and references
therein.
7 (a) H. Clavier and S. P. Nolan, Chem.–Eur. J., 2007, 13, 8029;
(b) F. Boeda, X. Bantreil, H. Clavier and S. P. Nolan, Adv. Synth.
Catal., 2008, 350, 2959; (c) H. Clavier, C. A. Urbina-Blanco and
S. P. Nolan, Organometallics, 2009, 28, 2848; (d) L. Vieille-Petit,
X. Luan, M. Gatti, S. Blumentritt, A. Linden, H. Clavier,
S. P. Nolan and R. Dorta, Chem. Commun., 2009, 3783.
8 B. R. Galan, M. Pitak, M. Gembicky, J. B. Keister and S. T. Diver,
J. Am. Chem. Soc., 2009, 131, 6822.
9 (a) R. B. Bedford, C. S. J. Cazin and S. L. Hazelwood, Angew.
Chem., Int. Ed., 2002, 41, 4120; (b) R. B. Bedford, S. L. Hazelwood
and M. E. Limmert, Chem. Commun., 2002, 2610; (c) C.-Y. Ho and
T. F. Jamison, Angew. Chem., Int. Ed., 2007, 46, 782;
(d) O. Diebolt, V. Jurcık, R. C. da Costa, P. Braunstein,
´
L. Cavallo, S. P. Nolan, A. M. Z. Slawin and C. S. J. Cazin,
Organometallics, 2010, 29, 1443.
Our attention next focused on the challenging RCM of
hindered dienes. The catalytic system allowed the formation,
in essentially quantitative yields, of both tetra-substituted
olefins 12 and 13 at a Ru loading of only 0.1 mol% (1000 ppm).
Even for one of the most difficult malonate derivatives, RCM
is efficiently promoted as compound 16 was isolated in a good
yield using only 0.5 mol% of pre-catalyst. Considering the
growing interest for catalysts able to mediate difficult RCM at
low catalyst loadings,19 cis-Caz-1 proved to be superior to
reported pre-catalysts for the RCM leading to the hindered
compounds 12 and 13.
10 Ind-III is commercially available from Umicore.
11 IUPAC numbering was used, see ESIw for drawing.
12 Crystal data for cis-Caz-1: C45H57Cl2N2O3PRu, M = 876.87,
monoclinic, space group P21/c, a = 19.132 (2) A, b = 9.5576
(11) A, c = 24.397 (3) A, b = 104.451 (3)1, V = 4320.0 (9) A3,
Z = 4, rcalcd = 1.348 g cmꢀ3, m(MoKa) = 0.56 mmꢀ1, T =
125 (2) K, Rint = 0.132, 7916 unique reflections, R1 = 0.0897,
wR2 = 0.1676 for 5696 reflections with I 4 2s(I), R1 = 0.1341,
wR2 = 0.1900 for all data, GOF = 1.197.
13 S. T. Nguyen and R. H. Grubbs, J. Am. Chem. Soc., 1993, 115,
9858.
14 S. Pruhs, C. W. Lehmann and A. Furstner, Organometallics, 2004,
¨
23, 280.
¨
15 (a) M. Barbasiewicz, M. Bieniek, A. Michrowska, A. Szadkowska,
A. Makal, K. Wozniak and K. Grela, Adv. Synth. Catal., 2007,
In conclusion, a new type of ruthenium olefin metathesis
catalyst bearing a mixed NHC/P(OR)3 ligand system has been
described. These complexes display a fluxional behaviour, the
kinetic trans-product being transformed into its cis-isomer
upon heating. This represents, to the best of our knowledge,
the first example of an indenylidene complex bearing solely
monodentate ligands exhibiting a cis-configuration. Mecha-
nistic studies suggest that the formation of this isomer does
not proceed by a dissociative pathway. Catalytic studies
demonstrated that these systems are able to efficiently promote
RCM reactions using loadings as low as 200 ppm, and display
a much better longevity than state-of-the-art pre-catalysts
allowing completion of challenging reactions.20
´
349, 193; (b) T. Ung, A. Hejl, R. H. Grubbs and Y. Schrodi,
Organometallics, 2004, 23, 5399; (c) C. E. Diesendruck, E. Tzur,
A. Ben-Asuly, I. Goldberg, B. F. Straub and N. G. Lemcoff, Inorg.
Chem., 2009, 48, 10819.
16 Details are given in the ESIw.
17 Complex used in catalysis was a 9/1 mixture of trans/cis-Caz-1.
18 Conversions were determined by GC analysis based on substrate
11.
19 (a) M. Gatti, L. Vieille-Petit, X. Luan, R. Mariz, E. Drinkel,
A. Linden and R. Dorta, J. Am. Chem. Soc., 2009, 131, 9498;
(b) K. M. Kuhn, T. M. Champagne, S. H. Hong, W.-H. Wei,
A. Nickel, C. W. Lee, S. C. Virgil, R. H. Grubbs and
R. L. Pederson, Org. Lett., 2010, 12, 984; (c) V. Sashuk,
L. H. Peeck and H. Plenio, Chem.–Eur. J., 2010, 16, 3983–3993.
20 cis-Caz-1 is commercially available from STREM and Umicore.
c
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 7115–7117 7117