Towards long-living metathesis catalysts by tuning the N-heterocyclic carbene (NHC) ligand on trifluoroacetamide-activated boomerang ru complexes

Article abstract of DOI:10.1002/ejoc.200900407

The synthesis and characterization of three novel trifluoromethylamido- containing "boomerang" precatalysts bearing various N-heterocyclic carbene (NHC) ligands are reported. Comparative kinetic and stability studies show the significant effect of the NHC on the catalyst reaction profile. An investigation of the reaction scope for diverse metathesis transformations has allowed us to establish the influence of the NHC on catalyst activity, especially as a function of substrate steric bulk. The excellent stability of one of the novel precatalysts is disclosed, and allowed for its recovery at the end of catalytic reactions. Large-scale ring-closing metathesis, enyne-metathesis and cross-metathesis experiments have revealed the recoverability of the catalyst. ICP-MS analyses of the synthesized products reveal Ru contamination levels of less than 2.5 ppm.

Full text of DOI:10.1002/ejoc.200900407

FULL PAPER
DOI: 10.1002/ejoc.200900407
Towards Long-Living Metathesis Catalysts by Tuning the N-Heterocyclic
Carbene (NHC) Ligand on Trifluoroacetamide-Activated Boomerang Ru
Complexes
Hervé Clavier,[a,b] Fréderic Caijo,[c] Etienne Borré,[d] Diane Rix,[d] Fabien Boeda,[a]
Steven P. Nolan,*[a,b] and Marc Mauduit*[d]
Keywords: Boomerang catalysts / Metathesis / Carbene ligands / Heterocycles / Recycling / Ruthenium
The synthesis and characterization of three novel trifluoro-
methylamido-containing “boomerang” precatalysts bearing
various N-heterocyclic carbene (NHC) ligands are reported.
Comparative kinetic and stability studies show the signifi-
cant effect of the NHC on the catalyst reaction profile. An
investigation of the reaction scope for diverse metathesis
transformations has allowed us to establish the influence of
the NHC on catalyst activity, especially as a function of sub-
strate steric bulk. The excellent stability of one of the novel
precatalysts is disclosed, and allowed for its recovery at the
end of catalytic reactions. Large-scale ring-closing metathe-
sis, enyne-metathesis and cross-metathesis experiments
have revealed the recoverability of the catalyst. ICP-MS
analyses of the synthesized products reveal Ru contami-
nation levels of less than 2.5 ppm.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
2-ylidene (SIMes) and 1,3-bis(2,4,6-trimethylphenyl)-
imidazol-2-ylidene (IMes) were introduced into the coordi-
nation sphere of the ruthenium metal center of both benzyl-
idene and boomerang catalysts leading to complexes 1a,[6]
1b,[7] and 2a[8] (Figure 1). Synthetic manipulations were car-
ried out to tune the NHC, for example, by using 1,3-bis(2,6-
diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene (SIPr),
Introduction
Over the past decade, ruthenium-mediated olefin metath-
esis has emerged as an indispensable tool in organic synthe-
sis for the formation carbon–carbon double bonds.[1] This
ubiquitous use of metathesis is clearly illustrated by the
large number of applications in natural product synthesis.[2]
The rapid development of this area has been punctuated by
ground-breaking developments involving well-defined ru-
thenium–carbene complexes. Of these, the benzylidene[3]
and boomerang-type catalysts[4] are most widely used. Fur-
ther improvements to the reactivity and stability of these
complexes have been achieved by the introduction of a N-
heterocyclic carbene (NHC) ligand.[5] Thus, the now well-
known 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-
1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene
(IPr)
(complexes 1c,[9] 1d,[10] and 2c[11]), and other NHC li-
gands.[12,13]
Catalysts of type 2 suffer from somewhat slow activation
kinetics. Some activated versions of the boomerang catalyst
have been developed based on either steric (complex 3a[14]
)
or electronic modulation of the coordination environment
(complexes 4a[15] and 5a[16]). We recently disclosed a series
of analogues of the Hoveyda complex 2a bearing an amino-
carbonyl group, for example, 6a, which have allowed signifi-
cant catalytic improvements.[17] Surprisingly, of these acti-
vated boomerang catalysts, only the SIMes NHC has been
employed so far.[18]
By appropriately substituting the styrenyl ether ligand,
which influences the catalyst activation step, and by varying
the NHC ligand, which can enhance the competence of the
active species, a simultaneous variation could very well al-
low the development of ever more efficient catalysts. More-
over, because styrenyl ether and NHC ligands control the
stability of the precatalyst and active species, respectively,
appropriate ligand selection could lead to longer-living cat-
alysts. Such a variation should allow for a decrease in the
often high catalyst loading required in most olefin metathe-
[a] Institute of Chemical Research of Catalonia (ICIQ),
Av. Països Catalans 16, 43007 Tarragona, Spain
[b] School of Chemistry, Purdie Building, University of St Andrews,
North Haugh, St Andrews, Fife, KY16 9ST, United Kingdom
Fax: +44-1334-463808
E-mail: sn17@st-andrews.ac.uk
[c] Ωcat SYSTEM®, Ecole Nationale Supérieure de Chimie de
Rennes,
Av. du Général Leclerc, 35700 Rennes, France
Fax: +33-2-23238108
E-mail: frederic.caijo@ensc-rennes.fr
[d] Sciences Chimiques de Rennes, UMR 6226 CNRS, Equipe Chi-
mie Organique et Supramoléculaire, Ecole Nationale Supéri-
eure de Chimie de Rennes,
Av. du Général Leclerc, 35700 Rennes, France
Fax: +33-2-23238108
E-mail: marc.mauduit@ensc-rennes.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900407.
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Towards Long-Living Metathesis Catalysts
Scheme 1. Synthesis of the Ru-based boomerang precatalysts 6.
1
The H NMR spectra of complexes 6a and 6c with satu-
rated NHC ligands have resonances at 4 ppm arising from
the imidazole protons, whereas the 1H NMR spectra of
complexes 6b and 6d with unsaturated NHC backbones dis-
play a single low-field resonance at around 7 ppm corre-
sponding to the imidazole ring protons. The proton of the
Ru=C carbenic carbon has a resonance at around 16.5 ppm
in all complexes, which is the shift expected for a Hoveyda-
type catalyst. This same proton is shifted to 19.5–20 ppm in
complexes 1a–d. The 13C NMR spectra of the unsaturated
complexes have a characteristic resonance arising from the
NHC carbenic carbon atom at around 175 ppm, whereas
the NHC carbenic carbon resonance for the saturated com-
plex is found at a lower field (around 210 ppm). All Ru=C
carbenic carbons resonate in the 282–292 ppm range.
The structures of the Ru-based complexes 6a–d were un-
ambiguously determined by single-crystal X-ray diffraction
studies. Ball-and-stick representations are depicted in Fig-
ure 2. Note that during the crystallization assays, complex
6c was found to be extremely stable. As an sample, five dif-
ferent solvent systems were tested without any precaution
or apparent catalyst decomposition. All the complexes
show the expected distorted square-based pyramidal geom-
etry around the metal center with coordination of the oxy-
gen to the ruthenium center. Selected bond lengths and
angles are provided in Table 1. The smaller N(1)–C(22)–
N(2) angles in IMes and IPr in comparison with those
found in SIMes and SIPr is a general feature observed be-
tween unsaturated and saturated NHC ligands.[21] Other
bond lengths and angles are similar for complexes 6a, 6b
and 6d, whereas 6c bearing SIPr shows deviations from
Figure 1. Representative NHC-containing Ru-based complexes for
olefin metathesis.
sis transformations.[19] It is clear that this high catalyst load-
ing requirement and associated elevated levels of ruthenium
contamination in the final organic products have with no
doubt delayed the industrial-scale use of olefin metathesis.
We report herein the synthesis and full characterization
of new NHC-containing boomerang-type complexes. A
beneficial pairing of a NHC ligand with the trifluoromethyl-
amide group has been achieved and excellent stability was
observed for one of the novel complexes. This enhanced
stability permits the recovery of the catalyst after catalytic
reactions. The catalytic activity of these new well-defined,
air-stable metathesis catalysts was evaluated and compared
in ring-closing-metathesis (RCM), enyne-metathesis, and
cross-metathesis (CM) reactions.
Results and Discussion
Synthesis and Characterization of the Catalysts
A metathesis reaction involving the previously described those of its congeners. For all the catalysts, the NHC (C)–
trifluoromethylamide-containing ligand 7[17] with a second- Ru and Ru=C bond lengths were found to be comparable
generation benzylidene complex 1a–d in the presence of to those previously reported in the literature for NHC-con-
CuCl afforded in good-to-excellent isolated yields com- taining “boomerang” complexes and are, respectively, in the
plexes 6a–d as microcrystalline green solids (Scheme 1). range of 1.82–1.84 and 1.96–2.00 Å.[8,13,17,21,22] The Ru–O
Note, 6a could also be synthesized from the ruthenium– bond lengths were found to vary: For complexes 6a, 6b,
indenylidene complex bearing SIMes[20] in a similar isolated and 6d the oxygen atom appears to coordinate tightly and
yield (90%).[17] In the case of the SIPr-containing catalyst distances in the range of 2.21–2.24 Å are found; the Ru–O
6c, we believe that the lower yield (61%) is due to the po- bond length in 6c is longer at 2.30 Å. The differences in the
orer stability in solution of its precursor 1c. As a testimony NHC backbones of SIMes and IMes do not lead to notice-
to their excellent stability, complexes 6a–d bearing SIMes, able variations in the bond lengths[21] whereas for SIPr and
IMes, SIPr, and IPr, respectively, were purified by silica gel IPr the Ru–O length varies by almost 0.1 Å. Moreover, the
chromatography using technical-grade pentane and acetone use of SIPr leads to variations in the Cl(1)–Ru(1)–Cl(2),
and could be handled in air.
C(1)–Ru(1)–C(22), and especially in the C(22)–Ru(1)–O(1)
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S. P. Nolan, M. Mauduit et al.
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angle (171°), which is one of the smallest angles reported in Table 1. Selected bond lengths [Å] and angles [°] for the Ru-based
complexes 6.
the literature (usual range 174–180°) for this moiety. To the
best of our knowledge, no X-ray structure of Hoveyda-type
complex bearing the SIPr ligand has been reported to date;
disparities observed in the bond lengths and angles of 6c
could be due to the SIPr ligand itself or to the combination Ru(1)–O(1)
of the SIPr and NHCOCF3 functions.
6a
6b
6c
6d
Ru(1)–C(1)
Ru(1)–C(22)
1.8338(9)
1.9852(8)
2.2383(7)
2.3315(3)
2.3537(3)
1.8318(12) 1.8266(14) 1.8301(12)
1.9960(12) 1.9911(13) 1.9846(13)
2.2374(9) 2.3002(10) 2.2111(10)
2.3467(3) 2.3293(4) 2.3300(4)
2.3558(3) 2.3358(4) 2.3412(4)
Ru(1)–Cl(1)
Ru(1)–Cl(2)
C(1)–Ru(1)–C(22)
103.42(4)
79.98(3)
175.27(4)
160.219(10)
107.14(7)
101.58(5) 99.75(6)
79.97(4) 78.27(5)
178.38(4) 171.09(4) 176.16(4)
162.376(12)153.478(14) 160.867(14)
103.58(10) 106.41(11) 103.40(11)
102.05(6)
80.36(5)
C(1)–Ru(1)–O(1)
C(22)–Ru(1)–O(1)
Cl(1)–Ru(1)–Cl(2)
N(1)–C(22)–N(2)
Reaction Profile and Stability Studies[23]
The reactivity profiles of these novel boomerang-type
catalysts, monitored by NMR spectroscopy, were then car-
ried out to gauge the influence of the NHC ligand on the
initiation and the overall reaction. The 2-allyl-2-methallyl-
malonate 8 was chosen as a benchmark substrate for ring-
closing metathesis carried out at 30 °C in CD2Cl2 using
1 mol-% catalyst (Figure 3). Interestingly, whereas after 1 h
of reaction no striking differences in the conversions were
observed, the reactivity profiles were found to be quite dis-
tinct. As expected,[24] complexes 6a and 6c bearing the satu-
rated NHCs SIMes and SIPr, respectively, were found to be
more active than their unsaturated NHC-containing conge-
ners 6b and 6d. In spite of an initial induction period of
5 min, complexes 6c and 6d with the more bulky NHCs
SIPr and IPr[25] reached full conversion before their SIMes
and IMes analogues. After this initial period of low activity
for 6c and 6d, the reaction rates increase and the conver-
sions surpass those of 6a and 6b after 20 (70% conversion)
and 45 min (75% conversion), respectively. This particular
reaction profile might be an indication of the enhanced sta-
bility of precatalysts 6c and 6d.
Figure 3. RCM of trisubstituted olefin 8 with precatalysts 6a–d
(1 mol-%) in CD2Cl2 (0.1 ) at 30 °C: ᭡ 6a; ᭿ 6b; ᭹ 6c; + 6d. The
Figure 2. Ball-and-stick representations of complexes 6 (most hy-
drogen atoms have been omitted for clarity).
1
conversions were monitored by H NMR spectroscopy.
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Towards Long-Living Metathesis Catalysts
These reactions were repeated under identical conditions
but at 45 °C. Toluene, the customary solvent for catalysis at
elevated temperatures, was also used; the reaction profiles
are presented in Figure 4. The change in temperature was
found to have a crucial influence on the reaction outcome.
A short induction period was again observed for 6c and 6d
bearing SIPr and IPr but the reactions reached completion
after 30 min whereas 6a and 6b did not reach conversions
of 50% in the same time interval. The differences in the
reactivity can be attributed to either the improved stability/
activity of 6c and 6d at 45 °C or to the solvent (catalyst
solubility). In either case, smaller differences in activity
were observed between saturated and unsaturated NHC li-
gands at elevated temperatures.
Figure 5. Reaction profiles of the RCM of 8 with precatalysts 2c
and 6c (1 mol-%) as a function of temperature: + 2c, 30 °C,
CD2Cl2, 0.1 ; ᭿ 2c, 45 °C, [D8]toluene, 0.1 ; o 2c, 60 °C, [D8]-
toluene 0.1 ; ᭹ 6c, 30 °C, CD2Cl2, 0.1 ; ᭡ 6c, 45 °C, [D8]toluene,
0.1 ; χ 6c, 60 °C, [D8]toluene, 0.1 . The conversions were moni-
1
tored by H NMR spectroscopy.
tably, after roughly 5 min, it decomposed and the reaction
ceased. An 80% yield of 9 could be achieved at 30 °C but
heating the reaction to 45 °C led to increased decomposi-
tion of 1c to give 25% conversion.
Figure 4. RCM of trisubstitued olefin 8 with precatalysts 6a–d
(1 mol-%) in [D8]toluene (0.1 ) at 45 °C: ᭡ 6a; ᭿ 6b; ᭹ 6c; + 6d.
1
The conversions were monitored by H NMR spectroscopy.
To examine the effect of the trifluoroacetamide group,
the reactivity profiles of catalysts 2c and 6c were monitored
at various temperatures (Figure 5).[26] Unexpectedly, cata-
lyst 2c showed an extremely poor activity at 30 °C (less than
10% of 9 was obtained after 1 h) whereas the reaction
reached completion after 40 min when using 6c. At 45 °C,
2c exhibited an improved activity (50% conversion after
1 h), but its analogue 6c, bearing the trifluoroacetamide
group, was far superior. At 60 °C, even smaller activity dif-
ferences between 2c and 6c were observed, which highlights
the fact that increasing the temperature moderates the effect
of the aryl-activating group. Intriguingly, the ability of the
aminocarbonyl group to enhance the activity of the boo-
merang catalysts was found to be modest when SIMes was
Figure 6. Reaction profiles of the RCM of 8 with precatalysts 1c
and 6c (1 mol-%) as a function of temperature: ᭿ 1c, 30 °C,
CD2Cl2, 0.1 ; + 1c, 45 °C, [D8]toluene, 0.1 ; ᭹ 6c, 30 °C,
CD2Cl2, 0.1 ; ᭡ 6c, 45 °C, [D8]toluene, 0.1 . The conversions
1
were monitored by H NMR spectroscopy.
Finally we compared boomerang catalysts 6a and 6c to
used as the ligand,[17] whereas the use of complexes bearing the commercially available second-generation Grubbs and
SIPr led to enhanced catalytic behavior.
Hoveyda complexes 1a and 2a for the RCM reaction involv-
The reaction with boomerang catalyst 6c was also com- ing diallyltosylamine (10) at 0 °C (Figure 7).[26] Under these
pared with its benzylidene counterpart 1c at 30 and 45 °C conditions, the reaction profiles of 6a and 6c were similar
(Figure 6).[26] The poor stability of 1c in solution is evident. to those obtained for the RCM of 8 at 45 °C, that is, in
Complex 1c showed an excellent initial activity but regret- spite of a longer initial activation period 6c reached full
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conversion before its SIMes analogue. Both 6a and 6c were absence of substrate and at several temperatures. As antici-
found to display significantly higher activity than 2a and pated, the benzylidene complex 1c exhibited rapid and com-
even more compared with 1a.
plete decomposition after only 5 min in [D4]dichloroethane
solution at room temperature. This was supported by H
1
NMR spectroscopy, which showed the loss of the character-
istic signal of the benzylidene proton at δ = 20 ppm, and
also by a change in the color of the solution from purple
to black. On the other hand, 6c was found to be highly
stable in solution because a single sample could be heated at
60 °C for 20 min, then at 80 °C, and finally stored at room
temperature for a week without any sign of decomposition.
Some catalyst degradation was observed by NMR spec-
troscopy after one month in solution, but complex 6c could
still be identified as the major component in solution.
Table 2. Stability of complexes 1c, 2c, 6a, and 6c under metathesis
conditions.
Figure 7. Reaction profiles of the RCM of 10 with precatalysts 1a,
2a, 6a, and 6c (1 mol-%) in CD2Cl2 (0.02 ) at 0 °C: ᭿ 1a; o 2a;
᭡ 6a; ᭹ 6c. The conversions were monitored by 1H NMR spec-
troscopy.
From the gathered data, the use of SIPr appears to be
beneficial and leads to a longer-living precatalyst 6c (see the
above synthesis, X-ray determination, and reaction profile
studies). The stability of 6c in solution was examined in the [a] Determined by NMR spectroscopy.
1
Figure 8. H NMR spectra of the metathesis reaction of 1,7-octadiene using 6c (C6D6, 400 MHz).
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Towards Long-Living Metathesis Catalysts
To further examine their stability, complexes 1c and 6c ester, amide, and ether groups was observed. However, the
were treated with an alkene substrate. The RCM reaction RCM of silyl ether 22 was not so straightforward (entry 7).
of 1,7-octadiene was examined (Table 2) to test the stability In the presence of this substrate, catalyst degradation oc-
of the precatalyst and the catalytic species. Indeed, the de- curred rapidly and consequently only the very stable and
gradation of metathesis-active species is well known to oc- active 6c gave a good isolated yield (88% in 1 h). Interest-
cur rapidly when all the substrate has been consumed. Thus, ingly, for the tetrasubstituted diene 24, the activity trends
we investigated the possibility of carrying out consecutive were reversed; catalysts 6a and 6b bearing the smaller NHC
metathesis runs by adding substrate after it has been con- exhibited a better performance, but the saturated NHC
sumed. This should provide information on the stability of complexes were still better than their unsaturated counter-
metathesis species under true reaction conditions. The start- parts. This confirms the close relationship between the ste-
ing material was added every 5 min in aliquots of 2 mmol to ric hindrance of the NHC ligand and the steric hindrance
a 5 mL C6D6 solution containing 0.5 mol-% of precatalyst. of the substrate.[13c,13d,24a]
RCM conversions were monitored by NMR spec-
troscopy.[27] The benzylidene-SIPr catalyst 1c showed rapid
degradation after the first cycle of substrate addition
(Table 2, entry 1), whereas the activated boomerang SIMes
complex 6a was able to perform two full metathesis reac-
tions. After the second cycle, the conversions decreased
Table 3. Comparison of the catalyst activities in the RCM of vari-
ous dienes.[a]
rapidly to reach only 74% by the fourth cycle (entry 2). Re-
markably, both SIPr complexes 2c and 6c were found to be
efficient in promoting metathesis reactions in six consecu-
tive cycles with quantitative conversions (entries 3 and 4).
Moreover, the characteristic signal of the benzylidene pro-
ton at δ = 16.6 ppm was still detected in the NMR spectrum
of the fifth run (Figure 8). This evidences the long lifetime
of both boomerang SIPr catalysts. Despite the increasing
concentration of olefin in the reaction mixture reaching up
to 2.8  by the seventh run (corresponding to a total of
14 mmol of consumed substrate for only 0.5 mol-% of cata-
lyst), 2c and 6c remained active and stable; no polymeriza-
tion products were detected. By the sixth cycle, some unre-
acted 1,7-octadiene was noticeable and this we take to indi-
cate the beginning of catalyst decomposition (see the NMR
spectra in Figure 8).
Reaction Scope
Next the scope of the metathesis transformations cata-
lyzed by the trifluoromethylamide-containing complexes
6a–d was investigated. The RCM reactions involving dienes
bearing various functional groups, the effect on the ring
size formed, and the influence of double bond substitution
(Table 3) were examined. Only slight differences in activity
were observed for reactions involving substrates requiring
short reaction times (less than 1 h; entries 1 and 3–6). How-
ever, in general, the trends observed in the reaction profile
studies were confirmed, that is, catalysts 6c and 6d bearing
SIPr and IPr ligands, respectively, are more active than 6a
and 6b. Moreover, the saturated NHC-containing com-
plexes (6a and 6c) are more active than the unsaturated
NHC analogues. The contrast is more significant for “diffi-
cult” substrates such as 12, which gives the seven-membered
ring 13. For this RCM, a slight thermal activation was nec-
essary with catalysts 6a and 6b, whereas 6c and 6d per-
formed well at room temperature within 15 min (entry 2).
The formation of five- to seven-membered rings with di- or
trisubstituted dienes was easily achieved and a tolerance to were used.
[a] Reaction conditions: 1 mol-% catalyst loading, CH2Cl2, 0.1 ,
25 °C. [b] Reactions performed at 40 °C. [c] 2 mol-% of catalyst
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The scope of the RCM was extended to several enynes catalyst loading. With alkene 34, cross metathesis with
using only 1 mol-% catalyst (Table 4). The reactivity with 2 equiv. of methyl acrylate and methyl vinyl ketone (en-
the selected substrates parallels the information obtained
on the precatalyst activity previously obtained in the RCM
of dienes. For a substrate such as 28 (entry 2), almost no
difference in reactivity was observed when using 6a–d as the
catalyst. However, with the sterically demanding enyne 30
catalysts 6a and 6b, with the smaller SIMes and IMes, pro-
vided significantly better isolated yields of 31 (entry 3).
However, 6c and 6d were found to be extremely competent
because a reaction time of only 1 h at room temperature
was required to complete the RCM of 26 (entry 1). On the
other hand, 6a and 6b provided 67 and 92% yields, respec-
tively, of the diene 27 after 24 h at 25 °C. Note, this repre-
sents an uncommon example of the superior activity of IM-
es- over SIMes-bearing catalysts.
Table 4. Comparison of the catalyst activities in the RCM of en-
ynes.[a]
As shown in Table 5, the activities of catalysts 6a–d were
also compared in the cross-metathesis reactions of terminal
alkenes and α,β-unsaturated olefins. Entry 1 corroborated
the superior catalytic performances of complexes bearing
SIPr and IPr over their SIMes and IMes analogues 6a and
[a] Reaction conditions: 1 mol-% catalyst loading, CH2Cl2, 0.1 ,
6b as reactions were completed in 0.5 h with only 1 mol-% 25 °C. [b] Reactions performed at 40 °C.
Table 5. Comparison of the catalyst activities in the cross-metathesis reactions.[a]
[a] Reaction conditions: 1 mol-% catalyst loading, CH2Cl2, 0.1 , 25 °C.
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Towards Long-Living Metathesis Catalysts
tries 2 and 5) using 6a and 6b gave good isolated yields (74– In this instance, 42 was the limiting reagent and so the for-
78%) of 35 and 39, respectively, as the single product with mation of self-metathesis product 44 (58%), which was ob-
the starting material 34 as the only other organic product served in all these reactions, becomes significant. As we were
observed. Unexpectedly, the same CM transformations car- wondering if 44 could act as a potential partner of this CM,
ried out with catalysts 6c and 6d led to the formation of a we employed 44 instead of 42 (entry 5). The reaction was
significant amount of the self-metathesis dimer 36 (ca. 30% found to proceed and a larger amount of 43 was obtained
with E/Z = 4:1, entries 2 and 5). This seems to be a result (54%). Note, the unreacted 44 recovered at the end of the
of the improved activity of the (S)IPr-containing catalysts. reaction with a decreased E/Z ratio lets us believe that the E
We attempted to circumvent the formation of this dimer by isomer might react faster than the Z isomer. An alternative
either using a larger excess of the deactivated olefin (en- explanation might be that the variation in the E/Z ratio
tries 3 and 6) or by employing a more active CM partner could result from a nonproductive metathesis. Because the
(entries 4 and 7). With catalyst 6c, both approaches lead 1,1-disubtituted partner is generally the most expensive one
to successful outcomes as only traces of the corresponding and in order to make the reaction more atom economic, a
dimers were observed by thin-layer chromatography. At this 41/44 ratio of 1:0.5 was employed and the catalyst activity
stage, the difference in reactivity between alkenes 34 and 37 was reinvestigated (entries 6 and 7). Under these conditions,
is due perhaps to the distance between the deactivating ester the contrast between SIMes and SIPr catalysts was found to
function and the C–C double bond.
be minute.
Having obtained encouraging results in the cross-meta-
thesis reactions, we proceeded to evaluate the performance
of catalysts in the challenging and scarcely studied formation
of trisubstituted double bonds by CM.[28] The CM between
1,1-disubstituted olefin 41 and activated partner 42 was se-
Catalyst Recovery Studies
As part of our research program directed towards cata-
lected as a benchmark reaction (Table 6). Because it had lyst recyclability and low ruthenium contamination of me-
been reported that 2c (5 mol-%) performed this reaction tathesis products,[21,30] the possibility of recovering the tri-
quantitatively in 24 h at 40 °C,[28c] we hoped to shorten the fluoroacetamide “boomerang” catalysts at the end of the
reaction time with our activated analogue 6c. Unfortunately, transformation was investigated. Hoveyda and co-workers
only traces of 43 were isolated (3%, entry 3) and even after have shown that “boomerang” catalysts such as 2a could
a reaction time of 24 h, significant product yields could not be isolated at the end of RCM in good-to-excellent yields
be obtained (10%, entry 2).[29] Nonetheless, we noticed again and could be reused thereafter.[4,8a] However, these experi-
for sterically demanding substrates that the SIMes-contain- ments were carried out using a relatively high catalyst load-
ing complex 6a (entry 1) performed better than its SIPr ing (up to 5 mol-%) and consequently it appears possible
counterpart 6c (entry 2). We then attempted to enhance the that the amount of catalyst recovered could represent the
formation of 43 by varying the reaction conditions. Inverting amount of precatalyst not activated. Moreover, these recov-
the olefin ratio led to an improved CM outcome (entry 4). ery tests were performed on quantities usually used for sub-
strate scope investigation (ca. 10 mg of catalyst used), which
does not allow for an accurate measure of the amount of
complex recovered. Bearing these facts in mind, catalyst re-
covery experiments were performed by using 50 mg catalyst
Table 6. The formation of trisubstituted olefins by cross metathe-
sis.[a]
loading, which corresponds to a 0.3 mol-% loading relative
to the substrate. Because ruthenium residue levels must be
less than 10 ppm for drug product synthesis,[31] the Ru con-
tent in metathesis transformation products was quantified
by ICP-MS analyses. As depicted in Equation (1), 50 mg
(0.3 mol-%) of the catalyst 6a bearing the SIMes ligand was
used in the RCM of 5.74 g of 8 in only 3 h at room tempera-
ture. After silica gel chromatography product 9 was isolated
in quantitative yield and contained a very low level of Ru
waste (δ = 0.24 ppm). Unfortunately, only 5 mg of 6a was
recovered (10% of the initial loading). The same experiment
was repeated with the SIPr-containing catalyst 6c with
20.3 mmol of 8 and an identical catalyst loading. In this
instance, the reaction reached completion in 2 h with a Ru
content in the product 9 of approximately 0.5 ppm [Equa-
tion (2)]. Silica gel purification and subsequent crystalli-
zation (octane/DCM) allowed 29 mg of 6c (58%) to be re-
1
covered in a pure form, as judged by its H NMR spec-
[a] Reaction conditions: 5 mol-% catalyst loading, CH2Cl2, 0.25 ,
40 °C. [b] 58% of dimer 44 was also isolated. [c] Dimer 44 was used
as the reaction partner instead of 42.
trum.[32] This residue was reused in catalysis and led to
identical catalytic behavior in a subsequent reaction.
Eur. J. Org. Chem. 2009, 4254–4265
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4261

S. P. Nolan, M. Mauduit et al.
FULL PAPER
(1)
(2)
(3)
(4)
The scope of catalyst 6c recovery was then extended to activating function and SIPr or IPr that allows for improved
enyne RCM and cross-metathesis reactions; see Equation (3)] catalyst activity and stability. The investigation of the reac-
and (4). In both cases, 0.3 mol-% of 6c was found to be suit- tion scope highlights the effect of the NHC because cata-
able for rapidly catalyzing the reaction and excellent isolated lysts 6c and 6d exhibited better catalytic performances in
yields were obtained with only a few ppm of residual ruthe- metathesis transformations involving less congested sub-
nium in the organic products. In addition, catalyst 6c was strates. On the other hand, catalysts 6a and 6b bearing
recovered in similar quantities as in the RCM of 8.
SIMes and IMes, respectively, were found to be more ef-
ficient for sterically hindered olefins. Attempts to form tri-
substituted C–C double bonds by CM afforded moderate
yields, but showed again the beneficial effect of the
Conclusions
We have described the synthesis of “boomerang”-type NHCOCF3 group. The possibility of recovering the catalyst
catalysts activated by a trifluoromethylamide function and at the end of metathesis transformations was examined by
bearing various sterically demanding NHCs (SIMes, IMes, performing large-scale reactions with low catalyst loadings.
SIPr, and IPr).[33] The complexes were obtained in a Catalyst 6c displayed a good reaction profile and an ability
straightforward manner and fully characterized by NMR to be recycled (52–58% of recovered catalyst for several re-
spectroscopy and X-ray diffraction studies. Activity profiles action types). Furthermore, Ru contamination in the final
of these catalysts were determined and compared with other organic products was found to be extremely low (less than
analogous complexes to clarify the role of both NHC and 2.5 ppm). In the light of this study, the development of
NHCOCF3 groups. It appears that the trifluoromethyl- complexes bearing novel NHC ligands, immobilized ver-
amide-activating effect is more important for the catalyst sions of catalyst 6c, and continuous flow processes involv-
bearing SIPr than for the one bearing the SIMes ligand. ing 6c appear promising and related ongoing investigations
Surprisingly, a matching effect was observed between the will be reported in due course.
4262
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4254–4265

Towards Long-Living Metathesis Catalysts
NMR (376 MHz, [D6]acetone, 25 °C, TMS): δ = –76.2 (s,
CF3) ppm. HRMS (ESI): calcd. for C35H39ClF3N4O2Ru 741.1757
[M – Cl + CH3CN]+; found 741.1735. C33H36Cl2F3N3O2Ru
(735.64): calcd. C 53.73, H 5.19, N 5.67; found C 53.05, H 5.17, N
5.40.
Experimental Section
General: All reagents were used as received. Dichloromethane
(DCM) and toluene were dispensed from a solvent purification sys-
tem from Innovative Technology. The catalysts were synthesized in
an MBraun glove-box containing dry argon and less than 1 ppm
oxygen or on a Schlenk line according to previously described pro-
cedures. Complexes 1b,[7a] 1c,[9b] and 1d[10] were synthesized accord-
ing to previously described procedures. Flash column chromatog-
[1,3-Bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene][2-isopropoxy-
5-(2,2,2-trifluoroacetamido)benzylidene]ruthenium(II) Chloride (6c):
Following the general procedure for complex 1c afforded the title
product (125 mg, 61% yield). 1H NMR (400 MHz, [D6]acetone,
25 °C, TMS): δ = 16.37 (s, 1 H, CH=Ru), 10.24 (s, 1 H, NH-CO),
7.92 [dd, 3J(H,H) = 8.9, 4J(H,H) = 2.5 Hz, 1 H, CHAr], 7.57 [t,
3J(H,H) = 7.7 Hz, 2 H, CHAr], 7.43 [d, 3J(H,H) = 7.7 Hz, 4 H,
raphy was performed on silica gel 60 (230–400 mesh). H, 13C and
1
19F NMR spectra were recorded with a Bruker Avance 400 Ultra-
shield NMR spectrometer. HRMS analyses were performed at the
ICIQ with a Waters LCT Premier or GCT mass spectrometer. Ele-
mental analyses were performed at the Universidad Complutense
de Madrid. The ICP-MS measurements were performed by the
UT2A Company, France. Substrates and products 8–21,[24b] 23–
31,[24b] 32,[34] 33,[15b] 34,[35] 35,[17] 36,[21] 37,[36] 40,[14a] 41,[37] 43,[28c]
and 44[38] have been described previously; for the others see the
Supporting Information.
4
3
CHAr], 7.31 [t, J(H,H) = 2.6 Hz, 1 H, CHAr], 7.11 [d, J(H,H) =
8.9 Hz, 1 H, CHAr], 5.03 [sept., 3J(H,H) = 6.1 Hz, 1 H, OCH-
(CH3)2], 4.32 (s, 4 H, CH2-CH2), 3.69 [sept., J(H,H) = 6.7 Hz, 1
3
H, CH(CH3)2NHC], 1.37 [d, 3J(H,H) = 6.1 Hz, 6 H, OCH-
(CH3)2], 1.28–1.22 (m, 24 H, CH3NHC) ppm. 13C NMR (100 MHz,
[D6]acetone, 25 °C, TMS): δ = 285.2 [d, J(C,Ru) = 12.3 Hz,
CH=Ru], 212.3 (NCN), 154.9 (CAr), 154.6 (CAr), 149.9 (NH-C=O),
149.1 (CAr), 144.0 (CAr), 137.0 (CAr), 131.2 (CAr), 131.1 (CAr),
129.6 (CHAr), 124.2 (CHAr), 121.3 (CHAr), 121.2 (CHAr), 116.1 [q,
J(C,F) = 285.6 Hz, CF3], 114.0 (CHAr), 113.9 (CAr), 113.2 (CHAr),
75.3 [OCH(CH3)2], 54.8 (CH2-CH2) 28.6 [CH(CH3)2NHC], 25.9
(CH3), 22.9 (CH3), 21.1 (CH3) ppm. 19F NMR (376 MHz,
[D6]acetone, 25 °C, TMS): δ = –76.2 (s, CF3) ppm. HRMS (ESI):
calcd. for C39H49F3N3O2Ru 750.2820 [M – Cl – HCl]+; found
750.2858. C39H50Cl2F3N3O2Ru (821.81): calcd. C 57.00, H 6.13, N
5.11; found C 56.67, H 6.09, N 5.03.
General Procedure for the Synthesis of the Catalysts: The styrenyl
ether ligand 7 (1 equiv.) in DCM solution (1 mL per 0.05 mmol of
ligand) was added to a solution of the Ru-based catalyst and cop-
per chloride (1.1 equiv.) in dry DCM (1 mL per 0.02 mmol of Ru
complex). The resulting mixture was stirred at 35 °C for 5 h. Vola-
tiles were removed under reduced pressure, acetone was added to
the residue, and the solution was filtered through a plug of Celite®.
The filtrate was concentrated and purified by chromatography on
silica gel (pentane/acetone, 75:25) to yield catalysts 6a–d as green
microcrystalline solids.
[1,3-Bis(2,6-diisopropylphenyl)-1H-imidazol-2(3H)-ylidene][2-iso-
propoxy-5-(2,2,2-trifluoroacetamido)benzylidene]ruthenium(II)
Chloride (6d): Following the general procedure for complex 1d af-
forded the title product (192 mg, 91% yield). H NMR (400 MHz,
[D6]acetone, 25 °C, TMS): δ = 16.47 (s, 1 H, CH=Ru), 7.94 [dt,
[1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene][2-isopropoxy-
5-(2,2,2-trifluoroacetamido)benzylidene]ruthenium(II) Dichloride
(6a): Following the general procedure for complex 1a afforded the
title product (237 mg, 88 % yield). 1 H NMR (400 MHz,
[D6]acetone, 25 °C, TMS): δ = 16.44 (s, 1 H, CH=Ru), 7.79 [dd,
1
4
3
3J(H,H) = 8.9 Hz, J(H,H) = 2.6 Hz, 1 H, CHAr], 7.66 [t, J(H,H)
= 7.8 Hz, 2 H, CHAr], 7.63 (s, 2 H, CHNHC), 7.49 [d, 3J(H,H) =
8.9 Hz, 4 H, CHAr], 7.66 [t, 4J(H,H) = 2.6 Hz, 1 H, CHAr], 7.12 [d,
4
4
3J(H,H) = 8.8, J(H,H) = 2.5 Hz, 1 H, CHAr], 7.61 [d, J(H,H) =
2.6 Hz, 1 H, CHAr], 7.08–7.06 (m, 5 H, CHAr), 4.97 [sept., 3J(H,H)
= 6.1 Hz, 1 H, CH(CH3)2], 4.28 (s, 4 H, CH2-CH2), 2.47 (s, 12 H,
3J(H,H) = 8.9 Hz, 1 H, CHAr], 5.03 [sept., J(H,H) = 6.1 Hz, 1 H,
3
CH3ortho), 2.43 (s, 6 H, CH3para), 1.26 [d, J(H,H) = 6.1 Hz, 6 H,
3
OCH(CH3)2], 3.17 [sept, 3J(H,H) = 6.8 Hz, 1 H, CH(CH3)2NHC],
CH(CH3)2] ppm. 13C NMR (100 MHz, [D6]acetone, 25 °C, TMS):
δ = 291.3 [d, J(C,Ru) = 12.3 Hz, CH, CH=Ru], 209.9 (NCN), 149.5
(C=O), 145.0 (CAr), 138.7 (CAr), 131.3 (CAr), 129.1 (CHAr), 121.1
(CHAr), 121.0 (CHAr), 116.0 [q, J(C,F) = 286.7 Hz, CF3], 114.2
(CHAr), 114.1 (CHAr), 113.2 (CHAr), 75.3 [CH(CH3)2], 51.4 (CH2),
20.6 (CH3), 20.3 (CH3) ppm. 19F NMR (376 MHz, [D6 ]-
acetone, 25 °C, TMS): δ = –76.2 (s, CF3) ppm. HRMS (ESI): calcd.
for C35H41ClF3N4O2Ru 743.1914 [M+ – Cl+CH3CN]; found
743.1926. C33H38Cl2F3N3O2Ru (737.65): calcd. C 53.73, H 5.19, N
5.67; found C 53.81, H 5.30, N 5.64.
3
3
1.40 [d, J(H,H) = 6.1 Hz, 6 H, OCH(CH3)2], 1.22 [d, J(H,H) =
6.8 Hz, 12 H, CH3NHC], 1.17 [d, 3J(H,H) = 6.8 Hz, 12 H,
CH3NHC] ppm. 13C NMR (100 MHz, [D6]acetone, 25 °C, TMS): δ
= 282.5 [d, J(C,Ru) = 12.6 Hz, CH=Ru], 175.9 (NCN), 149.9
(C=O), 148.1 (CHAr), 144.6 (CAr), 136.3 (CAr), 131.4 (CAr), 130.4
(CHAr), 126.9 (CHAr), 123.8 (CHAr), 120.7 (CHAr), 123.8 (CHAr),
116.1 [q, J(C,F) = 286.5 Hz, CF3], 113.5 (CHAr), 113.2 (CHAr),
75.5 [OCH(CH3)2], 28.6 [CH(CH3)2NHC], 25.6 (CH3), 22.3 (CH3),
21.0 (CH3) ppm. 19F NMR (376 MHz, [D6]acetone, 25 °C, TMS): δ
= –76.1 (s, CF3) ppm. HRMS (ESI): calcd. for C39H48ClF3N3O2Ru
784.2431 [M – Cl]+; found 784.2497. C39H48Cl2F3N3O2Ru (819.80):
calcd. C 57.14, H 5.90, N 5.13; found C 56.81, H 5.86, N 5.07.
[1,3-Dimesityl-1H-imidazol-2(3H)-ylidene][2-isopropoxy-5-(2,2,2-tri-
fluoroacetamido)benzylidene]ruthenium(II) Chloride (6b): Following
the general procedure for complex 1b afforded the title product
(110 mg, 82 % yield). 1H NMR (400 MHz, [D6]acetone, 25 °C,
TMS): δ = 16.57 (s, 1 H, CH=Ru), 7.80 [dd, 3J(H,H) = 9.0 Hz,
4J(H,H) = 2.5 Hz, 1 H, CHAr], 7.72 [d, 4J(H,H) = 2.5 Hz, 1 H,
CHAr], 7.49 (s, 2 H, CHAr), 7.17 (s, 4 H, CHAr), 7.11–7.09 (m, 2
General Procedure for the Reaction Profiling Studies: A NMR tube
equipped with a septum was charged with diethyl allyl(methallyl)-
malonate 8 (25 mg, 0.1 mmol) and CD2Cl2 or C2D4Cl2 (0.9 mL)
under argon. The sample was equilibrated at the required tempera-
ture in the NMR probe. The sample was locked and shimmed be-
fore the addition of the catalyst (100 µL, 1 µmol, 0.1  solution
of catalyst). The reaction progress was monitored by the periodic
acquisition of data over 1 h and integration of the characteristic
signals for the allylic proton resonances.
3
H, CHAr), 5.01 [sept., J(H,H) = 6.1 Hz, 1 H, CH(CH3)2], 2.50 (s,
3
12 H, CH3ortho), 2.26 (s, 6 H, CH3para), 1.34 [d, J(H,H) = 6.1 Hz,
6 H, CH(CH3)2] ppm. 13C NMR (100 MHz, [D6]acetone, 25 °C,
TMS): δ = 287.2 [d, J(C,Ru) = 12.4 Hz, CH=Ru], 174.2 (NCN),
149.6 (C=O), 145.2 (CAr), 139.5 (CAr), 139.2 (CAr), 137.9 (CAr),
136.2 (CAr), 131.5 (CAr), 129.2 (CHAr), 128.9 (CHAr), 125.3 (CHAr), Procedure for the Stability Studies: A Schlenk apparatus was filled
116.1 [q, J(C,F) = 286.7 Hz, CF3], 113.7 (CHAr), 113.3 (CHAr),
75.4 [CH(CH3)2], 20.7 (CH3), 20.3 (CH3), 18.4 (CH3) ppm. 19F
with the precatalyst (0.01 mmol) and the C6D6 solvent (5 mL) un-
der argon and then 1,7-octadiene (2 mmol, 300 µL) was added. Af-
Eur. J. Org. Chem. 2009, 4254–4265
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S. P. Nolan, M. Mauduit et al.
FULL PAPER
Pérez-Castells, Angew. Chem. Int. Ed. 2006, 45, 6086–6101; g)
A. H. Hoveyda, A. R. Zhugralin, Nature 2007, 450, 243–251;
h) S. Kotha, K. Lahiri, Synlett 2007, 2767–2784; i) P. Compain,
Adv. Synth. Catal. 2007, 349, 1829–1846.
P. Schwab, M. B. France, J. W. Ziller, R. H. Grubbs, Angew.
Chem. Int. Ed. Engl. 1995, 34, 2039–2041.
J. S. Kingsbury, J. P. A. Harrity, P. J. Bonitatebus, A. H. Hov-
eyda, J. Am. Chem. Soc. 1999, 121, 791–799.
a) S. P. Nolan (Ed.), N-Heterocyclic Carbenes in Synthesis,
Wiley-VCH, Weinheim, 2005, p. 304; b) F. Glorius (Ed.), N-
Heterocyclic Carbenes in Transition Metal Catalysis, Springer,
Berlin, Heidelberg, 2007, p. 231.
ter 5 min of reaction, a small amount (50 µL) of the reaction media
was taken for NMR monitoring followed by another loading of
1,7-octadiene (2 mmol). This procedure was repeated every 5 min.
until a significant amount of unconsumed starting material was
detected. All the aliquots were diluted in C6D6 (400 µL) and the
conversion of the cyclohexene product was measured by NMR
spectroscopy (see the NMR spectra in Figure 7).
[3]
[4]
[5]
General Procedure for the Metathesis Reactions: A Schlenk appara-
tus was filled with the substrate (0.5 mmol) [unactivated partner for
the cross-metathesis reactions (1–2.5 mmol)] and the solvent (5 mL)
(DCM for the reactions at room temp. and 40 °C, toluene for the
reactions at 80 °C) under argon and then the precatalyst (0.005–
0.01 mmol) was added. The progress of the reaction was monitored
by TLC. The solvent was removed under vacuum and the crude
residue was purified by flash column chromatography to yield the
pure product. For the synthesis of trisubstituted alkenes by CM,
the reported procedure was used.[28c]
[6]
[7]
M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999,
1, 953–956.
a) J. Huang, E. D. Stevens, S. P. Nolan, J. L. Petersen, J. Am.
Chem. Soc. 1999, 121, 2674–2678; b) M. Scholl, T. M. Trnka,
J. P. Morgan, R. H. Grubbs, Tetrahedron Lett. 1999, 40, 2247–
2250.
a) S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J.
Am. Chem. Soc. 2000, 122, 8168–8179; b) S. Gessler, S. Randl,
S. Blechert, Tetrahedron Lett. 2000, 41, 9973–9976.
a) A. Fürstner, L. Ackermann, B. Gabor, R. Goddard, C. W.
Lehmann, R. Mynott, F. Stelzer, O. R. Thiel, Chem. Eur. J.
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[8]
[9]
General Procedure for the Large-Scale Metathesis Reactions: A
500 mL round-bottomed flask was filled with the substrate
(22.6 mmol for 6a, 20.3 mmol for 6c), [methyl vinyl ketone for the
cross-metathesis reactions (40.6 mmol)] and DCM (200 mL) under
argon and then the catalyst (50 mg) was added. The progress of the
reaction was monitored by TLC. The solvent was removed under
vacuum and the crude residue was purified by flash column
chromatography (pentane/Et2O, 9:1) to yield the pure product and
then the column was eluted with pentane/acetone (75:25) to yield
the catalyst, which was subsequently recrystallized from DCM/oc-
tane (1:2).
[10]
[11]
[12]
L. Jafarpour, E. D. Stevens, S. P. Nolan, J. Organomet. Chem.
2000, 606, 49–54.
F. C. Courchay, J. C. Sworen, K. B. Wagener, Macromolecules
2003, 36, 8231–8239.
For representative examples with Grubbs catalysts 1, see: a) T.
Weskamp, F. J. Kohl, W. Hieringer, D. Gleich, W. A. Herrm-
ann, Angew. Chem. Int. Ed. 1999, 38, 2416–2419; b) T. M.
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Vander Mierde, C. Vercaemst, F. Verpoort, Chem. Eur. J. 2006,
12, 4654–4661; d) A. P. Blum, T. Riter, R. H. Grubbs, Organo-
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Supporting Information (see also the footnote on the first page of
this article): Synthetic procedures and characterization of the new
compounds 22, 23, 36, and 39, and all kinetic data.
Acknowledgments
2008, 14, 5465–5481; g) ref.[9a]
.
Funding for this project was generously provided by the European
Community through the seventh framework program (grant no.
CP-FP 211468-2 EUMET). This work was supported by the Centre
National de la Recherche Scientifique (CNRS), the Region Bret-
agne (grant to D. R.), the Agence Nationale de la Recherche (“Chi-
mie Pour le Développement Durable” program) and the Ministère
de la Recherche et de la Technologie. M. M. and F. C. thank Bre-
tagne Valorisation for financial support in the development of the
metathesis catalysts. S. P. N. (research grant) and H. C. (postdoc-
toral fellowship) both acknowledge the Spanish Ministerio de Edu-
cación y Ciencia (MEC) as well as the ICIQ Foundation for partial
support of this work. S. P. N. was an ICREA Research Professor.
We also thank Dr. Jordi Benet Buchholz and Mr. Eduardo C. Escu-
dero-Adán for the X-ray structure determinations.
[13]
For selected examples with Hoveyda-type catalysts 2, see: a) N.
Ledoux, A. Linden, B. Allaert, H. Vander Mierde, F. Verpoort,
Adv. Synth. Catal. 2007, 349, 1692–1700; b) D. R. Anderson,
V. Lavallo, D. J. O’Leary, G. Bertrand, R. H. Grubbs, Angew.
Chem. Int. Ed. 2007, 46, 7262–7265; c) J. M. Berlin, K.
Campbell, T. Ritter, T. W. Funk, A. Chlenov, R. H. Grubbs,
Org. Lett. 2007, 9, 1339–1342; d) I. C. Stewart, T. Ung, A. A.
Pletnev, J. M. Berlin, R. H. Grubbs, Y. Schrodi, Org. Lett.
2007, 9, 1589–1592; e) C. K. Chung, R. H. Grubbs, Org. Lett.
2008, 10, 2693–2696; f) G. C. Vougioukalakis, R. H. Grubbs,
J. Am. Chem. Soc. 2008, 130, 2234–2245.
a) H. Wakamatsu, S. Blechert, Angew. Chem. Int. Ed. 2002, 41,
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a) K. Grela, S. Harutyunyan, A. Michrowska, Angew. Chem.
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Harutyunyan, V. Sashuk, G. Dolgonos, K. Grela, J. Am. Chem.
Soc. 2004, 126, 9318–9325.
[14]
[15]
[1] For reviews on metathesis, see: a) A. Fürstner, Angew. Chem.
Int. Ed. 2000, 39, 3013–3043; b) T. M. Trnka, R. H. Grubbs,
Acc. Chem. Res. 2001, 34, 18–29; c) R. H. Grubbs (Ed.), Hand-
book of Metathesis, Wiley-VCH, Weinheim, 2003, p. 1204; d)
D. Astruc, New J. Chem. 2005, 29, 42–56; e) P. H. Deshmukh,
S. Blechert, Dalton Trans. 2007, 2479–2491.
[2] For reviews on synthetic applications, see: a) A. Deiters, S. F.
Martin, Chem. Rev. 2004, 104, 2199–2238; b) M. D. McReyn-
olds, J. M. Dougherty, P. R. Hanson, Chem. Rev. 2004, 104,
2239–2258; c) K. C. Nicolaou, P. G. Bulger, D. Sarlah, Angew.
Chem. Int. Ed. 2005, 44, 4490–4527; d) P. Van de Weghe, P.
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4264
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Towards Long-Living Metathesis Catalysts
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[26] Catalysts 1c and 2c are not commercially available, for the ki-
netic studies we used homemade complexes synthesized ac-
cording to the procedures reported in refs.[9b,11]; the purities
were found to be above 99% (see NMR spectra in the Support-
ing Information). Catalysts 1a and 2a were purchased from
Aldrich.
[27] Of note, the resulting cyclohexene product could not be re-
moved from the reaction medium during this experiment due
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strate and the styrenyl ligand 7 during the solvent evaporation.
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[32] See the Supporting Information.
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Received: April 14, 2009
Published Online: July 6, 2009
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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