Synthesis and activity of ruthenium olefin metathesis catalysts coordinated with thiazol-2-ylidene ligands

Article abstract of DOI:10.1021/ja075849v

A new family of ruthenium-based olefin metathesis catalysts bearing a series of thiazole-2-ylidene ligands has been prepared. These complexes are readily accessible in one step from commercially available (PCy ₃)₂Cl₂Ru=CHPh or (PCy₃)Cl ₂Ru=CH(o-iPrO-Ph) and have been fully characterized. The X-ray crystal structures of four of these complexes are disclosed. In the solid state, the aryl substituents of the thiazole-2-ylidene ligands are located above the empty coordination site of the ruthenium center. Despite the decreased steric bulk of their ligands, all of the complexes reported herein efficiently promote benchmark olefin metathesis reactions such as the ring-closing of diethyldiallyl and diethylallylmethallyl malonate and the ring-opening metathesis polymerization of 1,5-cyclooctadiene and norbornene, as well as the cross metathesis of allyl benzene with cis-1,4-diacetoxy-2-butene and the macrocyclic ring-closing of a 14-membered lactone. The phosphine-free catalysts of this family are more stable than their phosphine-containing counterparts, exhibiting pseudo-first-order kinetics in the ring-closing of diethyldiallyl malonate. Upon removing the steric bulk from the ortho positions of the N-aryl group of the thiazole-2-ylidene ligands, the phosphine-free catalysts lose stability, but when the substituents become too bulky the resulting catalysts show prolonged induction periods. Among five thiazole-2-ylidene ligands examined, 3-(2,4,6-trimethylphenyl)-and 3-(2,6-diethylphenyl)-4,5-dimethylthiazol-2- ylidene afforded the most efficient and stable catalysts. In the cross metathesis reaction of allyl benzene with cis-1,4-diacetoxy-2-butene increasing the steric bulk at the ortho positions of the N-aryl substituents results in catalysts that are more Z-selective.

Full text of DOI:10.1021/ja075849v

Published on Web 01/26/2008
Synthesis and Activity of Ruthenium Olefin Metathesis
Catalysts Coordinated with Thiazol-2-ylidene Ligands
Georgios C. Vougioukalakis and Robert H. Grubbs*
Contribution from the Arnold and Mabel Beckman Laboratory of Chemical Synthesis,
DiVision of Chemistry and Chemical Engineering, California Institute of Technology,
Pasadena, California 91125
Received August 15, 2007; E-mail: rhg@caltech.edu
Abstract: A new family of ruthenium-based olefin metathesis catalysts bearing a series of thiazole-2-ylidene
ligands has been prepared. These complexes are readily accessible in one step from commercially available
(PCy3)2Cl2RudCHPh or (PCy3)Cl2RudCH(o-iPrO-Ph) and have been fully characterized. The X-ray crystal
structures of four of these complexes are disclosed. In the solid state, the aryl substituents of the thiazole-
2-ylidene ligands are located above the empty coordination site of the ruthenium center. Despite the
decreased steric bulk of their ligands, all of the complexes reported herein efficiently promote benchmark
olefin metathesis reactions such as the ring-closing of diethyldiallyl and diethylallylmethallyl malonate and
the ring-opening metathesis polymerization of 1,5-cyclooctadiene and norbornene, as well as the cross
metathesis of allyl benzene with cis-1,4-diacetoxy-2-butene and the macrocyclic ring-closing of a
14-membered lactone. The phosphine-free catalysts of this family are more stable than their phosphine-
containing counterparts, exhibiting pseudo-first-order kinetics in the ring-closing of diethyldiallyl malonate.
Upon removing the steric bulk from the ortho positions of the N-aryl group of the thiazole-2-ylidene ligands,
the phosphine-free catalysts lose stability, but when the substituents become too bulky the resulting catalysts
show prolonged induction periods. Among five thiazole-2-ylidene ligands examined, 3-(2,4,6-trimethylphenyl)-
and 3-(2,6-diethylphenyl)-4,5-dimethylthiazol-2-ylidene afforded the most efficient and stable catalysts. In
the cross metathesis reaction of allyl benzene with cis-1,4-diacetoxy-2-butene increasing the steric bulk at
the ortho positions of the N-aryl substituents results in catalysts that are more Z-selective.
Chart 1. Ruthenium-Based Olefin Metathesis Catalysts
Introduction
Olefin metathesis is among the most versatile and powerful
methods for the construction of new carbon-carbon double
bonds.1 Over the past decade, olefin metathesis reactions have
been elegantly used by chemists working in a wide variety of
research fields, including industry and academia, to develop
novel synthetic routes and polymeric structures, as well as new
materials and industrial processes.2 The increased popularity of
this transformation has resulted from the development of well-
defined ruthenium-based catalysts with high air and moisture
stability and functional group tolerance.1
The synthesis of the first well-defined ruthenium-based olefin
metathesis initiator (1, Chart 1) was published in 1992.3
Although the basic structure of the currently used ruthenium-
based catalysts still resembles that original complex, i.e.,
comprised of a ruthenium alkylidene, two halides, and two
neutral ligands, contemporary catalysts (2-5, Chart 1) are
significantly more reactive and more tolerant of oxygen and
moisture. For instance, the commercially available complex 2,
although not as reactive, has much better functional group
compatibility than all of the early transition metal olefin
metathesis initiators.4 Substitution of one tricyclohexylphosphine
ligand with the bulky N-heterocyclic carbene (NHC) ligand H2-
(1) (a) Ivin, K. J.; Mol, J. C. Olefin Metathesis and Metathesis Polymerization;
Academic Press: San Diego, CA, 1997. (b) Grubbs, R. H. Handbook of
Metathesis; Wiley-VCH: Weinheim, Germany, 2003.
(2) For some representative reviews on the applications of olefin metathesis,
see: (a) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28,
446-452. (b) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997,
36, 2037-2056. (c) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413-
4450. (d) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371-
388. (e) Ivin, K. J. J. Mol. Catal. A: Chem. 1998, 133, 1-16. (f)
Buchmeiser, M. R. Chem. ReV. 2000, 100, 1565-1604. (g) Fu¨rstner, A.
Angew. Chem., Int. Ed. 2000, 39, 3012-3043. (h) Trnka, T. M.; Grubbs,
R. H. Acc. Chem. Res. 2001, 34, 18-29. (i) Connon, S. J.; Blechert, S.
Angew. Chem., Int. Ed. 2003, 42, 1900-1923. (j) Schrock, R. R.; Hoveyda,
A. H. Angew. Chem., Int. Ed. 2003, 42, 4592-4633. (k) Grubbs, R. H.
Tetrahedron 2004, 60, 7117-7140. (l) Donohoe, T. J.; Orr, A. J.; Bingham,
M. Angew. Chem., Int. Ed. 2006, 45, 2664-2670.
(3) Nguyen, S. T.; Johnson, L. K.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1992, 114, 3974-3975.
9
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J. AM. CHEM. SOC. 2008, 130, 2234-2245
10.1021/ja075849v CCC: $40.75 © 2008 American Chemical Society

Ruthenium Olefin Metathesis Catalysts
A R T I C L E S
Chart 2. Ruthenium-Based Olefin Metathesis Catalysts
IMes to produce 3 (Chart 1) led to a significant improvement
of catalytic activity, while maintaining the high functional group
tolerance and stability of 2.5 This improvement has been
attributed to the increased affinity of the NHC-substituted
ruthenium center for π-acidic olefins relative to σ-donating
phosphines.6 The development of phosphine-free complexes7
has yielded olefin metathesis catalysts 4 and 5 (Chart 1) that
display even higher thermal stability.8 Subsequent studies led
to the development of ruthenium-based catalysts for asymmetric
olefin metathesis reactions,9 and for applications in aqueous and
protic solvent systems.10 Last, the formation of tetrasubstituted
carbon-carbon double bonds typically requires high catalyst
loadings and elevated reaction temperatures, comprising one of
the major limitations for most ruthenium catalysts. Intense effort
has recently led to the development of a series of catalysts
capable of successfully carrying out this very challenging task.11
Coordinated with Carbene Ligandsa
Herein we report the synthesis and complete characterization
of seven new, ruthenium-based olefin metathesis initiators,
coordinated with a series of thiazole-2-ylidene ligands. To the
best of our knowledge, this is the first report on ruthenium-
based olefin metathesis catalysts bearing carbene ligands with
only one exocyclic substituent adjacent to the carbenic center.
The catalytic performance of these thiazole-2-ylidene-bearing
complexes has been evaluated in ring-closing metathesis, cross
metathesis, and ring-opening metathesis polymerization reac-
tions. Some complexes display efficiencies similar to the
a The dashed lines in the structures indicate that the coordinating ligand
L may or may not be connected to the phenyl ring of the benzylidene.
commercially available second-generation catalysts. The phos-
phine-free members of this new family of catalysts exhibit
unexpectedly high stability. In the cross metathesis reaction of
allyl benzene with cis-1,4-diacetoxy-2-butene, the bulkier thia-
zole-2-ylidene ligands afford complexes that display an in-
creased Z-selectivity, compared to the less bulky ones.
(4) (a) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 2039-2041. (b) Schwab, P.; Grubbs, R. H.; Ziller,
J. W. J. Am. Chem. Soc. 1996, 118, 100-110.
(5) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953-
956.
Results and Discussion
(6) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123,
6543-6554.
Electron-rich and bulky N-heterocyclic carbenes (NHCs)
display excellent σ-donating ability and resemble the properties
of electron-rich phosphines.12 As such, they have been exten-
sively utilized in the preparation of many synthetically useful
organometallic catalysts.13 Chart 2 summarizes the carbenic
frameworks that have been used thus far in ruthenium-based
olefin metathesis initiators. The most successful and well-studied
catalysts, bear either a symmetrical or unsymmetrical imidazol-
or imidazolin-2-ylidene.14 Triazol-5-ylidenes,14e,g tetrahydropy-
rimidin-2-ylidenes,15 and a four-membered ring diaminocar-
bene16 have also been used, affording the corresponding
complexes (Chart 2). More recently, a series of ruthenium
complexes coordinated with cyclic(alkyl)(amino) carbenes,
displaying stability and activity comparable to standard olefin
metathesis catalysts, have been synthesized.17
(7) (a) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J., Jr.; Hoveyda, A.
H. J. Am. Chem. Soc. 1999, 121, 791-799. (b) Garber, S. B.; Kingsbury,
J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168-
8179. For representative examples of other phosphine-free catalysts, see:
(c) Wakamatsu, H.; Blechert, S. Angew. Chem., Int. Ed. 2002, 41, 2403-
2405. (d) Grela, K.; Harutyunyan, S.; Michrowska, A. Angew. Chem., Int.
Ed. 2002, 41, 4038-4040. (e) Michrowska, A.; Bujok, R.; Harutyunyan,
S.; Sashuk, V.; Dolgonos, G.; Grela, K. J. Am. Chem. Soc. 2004, 126,
9318-9325. (f) Hejl, A.; Day, M. W.; Grubbs, R. H. Organometallics 2006,
25, 6149-6154.
(8) For studies on the decomposition of ruthenium-based olefin metathesis
initiators, see: (a) Ulman, M.; Grubbs, R. H. J. Org. Chem. 1999, 64, 7202-
7207. (b) Hong, S. H.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc.
2004, 126, 7414-7415. (c) Hong, S. H.; Wenzel, A. G.; Salguero, T. T.;
Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2007, 129, 7961-7968. (d)
Hong, S. H.; Chlenov, A.; Day, M. W.; Grubbs, R. H. Angew. Chem., Int.
Ed. 2007, 46, 5148-5151. Stability of the first-generation catalyst in a
continuous flow reactor: (e) Lysenko, Z.; Maughon, B. R.; Mokhtar-Zadeh,
T.; Tulchinsky, M. L. J. Organomet. Chem. 2006, 691, 5197-5203.
(9) (a) Seiders, T. J.; Ward, D. W.; Grubbs, R. H. Org. Lett. 2001, 3, 3225-
3228. (b) Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda,
A. H. J. Am. Chem. Soc. 2002, 124, 4954-4955. (c) Van Veldhuizen, J.
J.; Gillingham, D. G.; Garber, S. B.; Kataoka, O.; Hoveyda, A. H. J. Am.
Chem. Soc. 2003, 125, 12502-12508. (d) Gillingham, D. G.; Kataoka, O.;
Garber, S. B.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 12288-12290.
(e) Van Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H.
J. Am. Chem. Soc. 2005, 127, 6877-6882. (f) Funk, T. W.; Berlin, J. M.;
Grubbs, R. H. J. Am. Chem. Soc. 2006, 128, 1840-1846. (g) Berlin, J.
M.; Goldberg, J. M.; Grubbs, R. H. Angew. Chem., Int. Ed. 2006, 45, 7591-
7595. (h) Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2007, 129,
3824-3825.
(10) (a) Lynn, D. M.; Mohr, B.; Grubbs, R. H.; Henling, L. M.; Day, M. W. J.
Am. Chem. Soc. 2000, 122, 6601-6609. (b) Lynn, D. M.; Grubbs, R. H.
J. Am. Chem. Soc. 2001, 123, 3187-3193. (c) Ro¨lle, T.; Grubbs, R. H.
Chem. Commun. 2002, 1070-1071. (d) Gallivan, J. P.; Jordan, J. P.;
Grubbs, R. H. Tetrahedron Lett. 2005, 46, 2577-2580. (e) Hong, S. H.;
Grubbs, R. H. J. Am. Chem. Soc. 2006, 128, 3508-3509. (f) Mwangi, M.
T.; Runge, M. B.; Bowden, M. B. J. Am. Chem. Soc. 2006, 128, 14434-
14435. (g) Binder, J. B.; Guzei, I. A.; Raines, R. T. AdV. Synth. Catal.
2007, 349, 395-404.
(11) (a) Berlin, J. M.; Campbell, K.; Ritter, T.; Funk, T. W.; Chlenov, A.; Grubbs,
R. H. Org. Lett. 2007, 9, 1339-1342. (b) Stewart, I. C.; Ung, T.; Pletnev,
A. A.; Berlin, J. M.; Grubbs, R. H.; Schrodi, Y. Org. Lett. 2007, 9, 1589-
1592.
Synthesis and Characterization: Despite the numerous
reports concerning carbene-bearing ruthenium-based olefin
metathesis initiators,18 a complex coordinated with a carbene
that has only one exocyclic substituent adjacent to the carbenic
center has not been reported. While we were initially concerned
that the decreased steric protection of such complexes might
(12) The first NHC complexes were reported in 1968: (a) O¨ lefe, K. J.
Organomet. Chem. 1968, 12, 42-43. (b) Wanzlick, H. W.; Scho¨nherr, H.
J. Angew. Chem., Int. Ed. Engl. 1968, 7, 141-142. The first stable NHC
was reported in 1991: (c) Arduengo, A. J., III; Harlow, R. J.; Kline, M. J.
Am. Chem. Soc. 1991, 113, 361-363.
(13) Review articles: (a) Herrmann, W. A.; Ko¨cher, C. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2162-2187. (b) Herrmann, W. A. Angew. Chem., Int. Ed.
2002, 41, 1290-1309. (c) Perry, M. C.; Burgess, K. Tetrahedron:
Asymmetry 2003, 14, 951-961. (d) Hahn, F. E. Angew. Chem., Int. Ed.
2006, 45, 1348-1352. (e) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M.
G. Angew. Chem., Int. Ed. 2007, 46, 2768-2813.
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A R T I C L E S
Vougioukalakis and Grubbs
Chart 3. New Ruthenium-Based Olefin Metathesis Catalysts
Scheme 1. Synthesis of 3-Aryl-4,5-dimethylthiazolium Chlorides
Coordinated with Thiazole-2-ylidene Ligands
cause them to be highly unstable and prone to degradation, we
were intrigued by this previously unevaluated steric environ-
ment. We chose to investigate 3-aryl-4,5-dimethylthiazol-2-
ylidenes as ligands, carrying out the synthesis of complexes
6-12 shown in Chart 3. To the best of our knowledge, the only
stable thiazol-2-ylidene was reported in 1997 by Arduengo and
co-workers.19 Thiazole-2-ylidenes have been also employed as
catalysts in organocatalytic transformations,20 and some ben-
zothiazolin-2-ylidenes have been used as ligands in other
transition metal complexes.21
As illustrated in Scheme 1, the synthesis of 3-aryl-4,5-
dimethylthiazolium chlorides that were used as carbene precur-
sors is straightforward. N-Formylation of commercially available
anilines afforded formanilides 13b-13e in high yields (13a is
commercially available),22 which were then reacted with
phosphorus pentasulfide and 3-chloro-2-butanone in dry dioxane
to afford the desired dimethylthiazolium chlorides 14a-14e.23
Complexes 6-12 were prepared in moderate to high yields
from the corresponding 3-aryl-4,5-dimethylthiazole-2-ylidenes,
using complexes 2 or 4 as ruthenium sources (Scheme 2). In
the case of complex 10, the appropriate carbene ligand was
prepared in situ by deprotonation of dimethylthiazolium salt 14e
with KHMDS. This intermediate carbene is the only reported
stable thiazole-2-ylidene at room temperature.19 For example,
the less sterically hindered 3-(2,4,6-trimethylphenyl)-4,5-dim-
ethylthiazol-2-ylidene, derived by the deprotonation of dimeth-
ylthiazolium salt 14c, is not as kinetically stable and dimerizes
quickly above 0 °C in solution.19 Indeed, none of the carbenes
formed via deprotonation of the dimethylthiazolium salts 14a-
14d were stable enough to afford the desired ruthenium
complexes 6-9 and 11-12 in a satisfactorily yield. For instance,
the typical isolated yields for complex 11 were lower than 9%,
even when the reaction was carried out at 0 °C, or when 2 equiv
of 14c/KHMDS, with respect to the ruthenium source, were
(14) Initiators bearing symmetrical imidazol-2-ylidene and imidazolin-2-ylidene
ligands: (a) Weskamp, T.; Schattenmann, W. C.; Spiegler, M.; Herrmann,
W. A. Angew. Chem., Int. Ed. 1998, 37, 2490-2493. (b) Huang, J.; Stevens,
E. D.; Nolan, S. P.; Petersen, J. L. J. Am. Chem. Soc. 1999, 121, 2674-
2678. (c) Huang, J.; Schanz, H. J.; Stevens, E. D.; Nolan, S. P.
Organometallics 1999, 18, 5375-5380. (d) Scholl, M.; Trnka, T. M.;
Morgan, J. P.; Grubbs, R. H. Tetrahedron Lett. 1999, 40, 2247-2250. (e)
Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, T. E.; Scholl, M.;
Choi, T. L.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003,
125, 2546-2558. (f) Love, J. A.; Sanford, M. S.; Day, M. W.; Grubbs, R.
H. J. Am. Chem. Soc. 2003, 125, 10103-10109. Also see refs 5, 9a, and
9f-g. Unsymmetrical catalysts: (g) Fu¨rstner, A.; Ackermann, L.; Gabor,
B.; Goddard, R.; Lehmann, C. W.; Mynott, R.; Stelzer, F.; Thiel, O. R.
Chem.sEur. J. 2001, 7, 3236-3253. (h) Dinger, M. B.; Nieczypor, P.;
Mol, J. C. Organometallics 2003, 22, 5291-5296. (i) Vehlow, K.;
Maechling, S.; Blechert, S. Organometallics 2006, 25, 25-28. (j) Ledoux,
N.; Allaert, B.; Pattyn, S.; Mierde, H. V.; Vercaemst, C.; Verpoort, F.
Chem.sEur. J. 2006, 12, 4654-4661. (k) Vougioukalakis, G. C.; Grubbs,
R. H. Organometallics 2007, 26, 2469-2472. (l) Ledoux, N.; Linden, A.;
Allaert, B.; Mierde, H. V.; Verpoort, F. AdV. Synth. Catal. 2007, 349, 1692-
1700.
(20) Recent representative examples: (a) Pesch, J.; Harms, K.; Bach, T. Eur. J.
Org. Chem. 2004, 2025-2035. (b) Kageyama, Y.; Murata, S. J. Org. Chem.
2005, 70, 3140-3147. (c) Liu, Y. K.; Li, R.; Yue, L.; Li, B. J.; Chen, Y.
C.; Wu, Y.; Ding, L. S. Org. Lett. 2006, 8, 1521-1524. (d) He, J.; Zheng,
J.; Liu, J.; She, X.; Pan, X. Org. Lett. 2006, 8, 4637-4640. (e) Li, G. Q.;
Dai, L. X.; You, S. L. Chem. Commun. 2007, 852-854.
(21) (a) Calo´, V.; Del Sole, R.; Nacci, A.; Schingaro, E.; Scordari, F. Eur. J.
Org. Chem. 2000, 869-871. (b) Raubenheimer, H. G.; Cronje, S. J.
Organomet. Chem. 2001, 617-618, 170-181. (c) Calo´, V.; Nacci, A.;
Monopoli, A.; Spinneli, M. Eur. J. Org. Chem. 2003, 1382-1385. (d) Calo´,
V.; Nacci, A.; Monopoli, A. J. Organomet. Chem. 2005, 690, 5458-5466.
(e) Huynh, H. V.; Meier, N.; Pape, T.; Hahn, F. E. Organometallics 2006,
25, 3012-3018.
(22) Kamer, P. C. J.; Nolte, R. J. M.; Drenth, W. J. Am. Chem. Soc. 1988, 110,
6818-6825.
(23) We used a modification of a procedure reported in the literature: (a)
Liebscher, J. 1,3-Thiazole. In Methoden der Organischen Chemie, 4th ed.;
Schaumann, E., Ed.; Georg Thieme Verlag: Stuttgart, 1994; Band E 8b,
Heratrene III/Part 2; pp 45-48. (b) Hromatka, O. U.S. Patent 2,160,867,
1939.
(15) (a) Yun, J.; Marinez, E. R.; Grubbs, R. H. Organometallics 2004, 23, 4172-
4173. (b) Yang, L.; Mayr, M.; Wurst, K.; Buchmeiser, M. R. Chem.sEur.
J. 2004, 10, 5761-5770.
(16) Despagnet-Ayoub, E.; Grubbs, R. H. Organometallics 2005, 24, 338-340.
(17) Anderson, D. R.; Lavallo, V.; O’Leary, D. J.; Bertrand, G.; Grubbs, R. H.
Angew. Chem., Int. Ed. 2007, 46, 7262-7265.
(18) For some recent highlights, see refs 14-17 and literature cited therein.
(19) Arduengo, A. J., III; Goerlich, J. R.; Marshall, W. J. Liebigs Ann./Recl.
1997, 365-374.
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Ruthenium Olefin Metathesis Catalysts
A R T I C L E S
Scheme 2. Synthesis of Ruthenium-Based Olefin Metathesis
Catalysts 6-12
Chart 4. Ruthenium-Based Complexes 15-17 (Observed in Situ)
complex 2. Complexes 15 and 16 (Chart 4) were formed in the
course of the reaction, as identified by 1H and 31P NMR
spectroscopy. However, complete decomposition of complexes
15 and 16 was observed in 2 and 18 h, respectively, at room
temperature. The analogous phosphine-containing ruthenium
complex bearing a 3-(2,6-diisopropylphenyl)-4,5-dimethylthi-
azol-2-ylidene was formed neither via transmetallation nor
through the in situ generation of the free carbene by deproto-
nation of the dimethylthiazolium salt 14e. Instead, only the
formation of complex 17 was observed by 1H NMR and high-
resolution mass spectroscopy (Chart 4).27 Apparently, coordina-
tion of the first bulky thiazol-2-ylidene ligand at the ruthenium
center, followed by the dissociation of the remaining tricyclo-
hexylphosphine and coordination of a second thiazol-2-ylidene,
is favorable due to the formation of an “empty pocket” in the
coordination sphere of the intermediate complex. This “empty
pocket” accommodates the second unsymmetrical carbene ligand
much better relative to the C3 symmetric tricyclohexylphosphine.
Complex 17 is not stable enough to be isolated by column
chromatography.
The molecular structure of complexes 6-9 was confirmed
by single-crystal X-ray crystallographic analysis (Figure 1).28
All complexes exhibit a distorted square pyramidal geometry
with the RudC benzylidene bond occupying the apical position
and the Cl atoms trans to one another. The bond lengths and
angles of 6-9 are quite similar to those of complex 5 (Table
1). However, the RusCthiazol-2-ylidene bond distance in 6-9 is
0.026-0.037 Å shorter than the RusCNHC bond distance in 5.
This difference is most likely due to the decreased steric bulk
of the thiazole-2-ylidene ligands compared to the H2IMes. This
hypothesis is supported by the increased RusCthiazol-2-ylidene
bond distance as the ligand increases in steric bulk (namely
going from 6 to 9). The dihedral angles between the thiazole-
2-ylidene and the isopropoxy styrene planes in complexes 6, 7,
and 9 range between 5° and 13° (Table 1, entry 8). This dihedral
angle is much larger in 8 (34°) as illustrated in the top view of
complex 8 shown in Figure 1. In the solid state, the aryl
substituent of the thiazole-2-ylidene ligand in complexes 6-9
is located above the empty coordination site of the ruthenium
center.28 This is rather interesting since the phosphine-free
ruthenium complexes reported thus far, bearing unsymmetrical
carbenes with only one exocyclic aryl substituent adjacent to
the carbenic center, are isolated with this aryl group being
directly above the benzylidene proton.14i,14l,17
added in portions. To circumvent the formation of the unstable
free carbenes (and their concomitant dimerization), the corre-
sponding silver-thiazole-2-ylidene complexes that have been
successfully used as NHC transfer reagents in the past were
prepared.24 These silver complexes were formed quantitatively
and then reacted in situ (with the ruthenium source) to afford
the desired ruthenium complexes 6-9 and 11-12 (see Experi-
mental Section).25 Interestingly, the same transmetallation
conditions do not yield complex 10, despite the quantitative
formation of the corresponding silver-thiazole-2-ylidene com-
plex.26 As expected, complexes 8 and 9 may also be prepared
from 11 and 12, respectively, via olefin metathesis with
o-isopropoxy-â-methylstyrene, albeit less efficiently compared
to their direct preparation using complex 4.
We also tried to synthesize and isolate the phosphine-
containing analogues of complexes 6, 7, and 10 via transmet-
allation between the corresponding silver compounds and
(24) (a) Wang, H. M. J.; Lin, I. J. B. Organometallics 1998, 17, 972-975. (b)
Lin, I. J. B.; Vasam, C. S. Comm. Inorg. Chem. 2004, 25, 75-129. (c) de
Fre´mont, P.; Scott, N. M.; Stevens, E. D.; Ramnial, T.; Lightbody, O. C.;
Macdonald, C. L. B.; Clyburne, J. A. C.; Abernethy, C. D.; Nolan, S. P.
Organometallics 2005, 24, 6301-6309. (d) Yu, X. Y.; Patrick, P. O.; James,
B. R. Organometallics 2006, 25, 2359-2363.
(25) 3-(3,5-Di-tert-butylphenyl)-4,5-dimethylthiazolium chloride was also pre-
pared; however, we were unable to generate its silver complex under the
conditions reported for the other dimethylthiazolium salts. Its deprotonation
with KHMDS in the presence of complex 2 did not afford any new
benzylidene species (NMR spectroscopy). When complex 4 was used as
the ruthenium source we were able to identify a new product in situ, most
probably derived from carbene bis-addition to the ruthenium center. This
species is not stable enough to be isolated by column chromatography.
For other reported ruthenium complexes derived from carbene bis-addition,
see ref 27.
(27) Carbene bis-substitution in analogous ruthenium complexes has been
reported in the past: refs 14a and 14e,f. Also see: Ledoux, N.; Allaert,
B.; Linden, A.; Van Der Voort, P.; Verpoort, F. Organometallics 2007,
26, 1052-1056.
(28) Low quality crystals of complex 10 were also obtained. Although highly
disordered, X-ray analysis on different samples of these single crystals
showed the same connectivity and orientation of the ligands as in the crystal
structures of the complexes 6-9.
(26) Formation of 10 was observed, although only after refluxing the silver-
thiazole-2-ylidene complex with complex 4 in CH2Cl2 overnight. Since 10
can be efficiently formed via the in situ deprotonation of dimethylthiazolium
salt 14e, we did not study the transmetallation route further.
9
J. AM. CHEM. SOC. VOL. 130, NO. 7, 2008 2237

A R T I C L E S
Vougioukalakis and Grubbs
Figure 1. Side view of the structures of complexes 6-9 and top view of complex 8 are shown. Displacement ellipsoids are drawn at 50% probability. For
clarity, most hydrogen atoms have been omitted.
Table 1. Selected Bond Lengths, Bond Angles, and Dihedral
Angles for Complexes 5-9a
entry
5
6
7
8
9
Bond Lengths (Å)
1
2
3
Ru-C(1)
Ru-C(11)
Ru-O
1.828 1.832 1.826 1.830 1.832
1.981 1.944 1.947 1.953 1.955
2.261 2.265 2.270 2.275 2.268
Bond Angles (deg)
4
5
6
7
C(1)-Ru-C(11)
C(11)-Ru-O
Cl(1)-Ru-Cl(2)
S-C(11)-Ru
101.5 94.7
176.2 174.3 173.9 173.0 173.2
156.5 154.4 155.7 159.0 154.6
94.7
95.8
94.6
n/a
Dihedral Angles (deg)
S-C(11)-Ru-C(1) n/a 8.2
126.6 127.8 121.0 124.4
8
13.2
34.0
5.1
a For a complete list of bond lengths and bond angles, refer to the
Supporting Information.
Ring-Closing Metathesis (RCM) Activity: RCM is the first
widely used olefin metathesis reaction in organic synthesis1b
and has been used to evaluate the efficiency of most ruthenium-
based catalysts.29 We initially studied the catalytic activity of
the new phosphine-containing complexes in the RCM of
diethyldiallyl malonate (18) to substituted cycloalkene 19
(Figure 2). Interestingly, the plots of cycloalkene 19 concentra-
tion vs time, for the RCM of 18 using catalysts 2-5 and 11-
12 in Figure 2, reveal that both 11 and 12 effect the cyclization
of 18. Nevertheless, these two new catalysts are less efficient
than complexes 2-5 due to their high decomposition rate,
clearly illustrated from the curvature in the logarithmic plot (ln-
Figure 2. RCM of diene 18 to disubstituted cycloalkene 19, using catalysts
2-5, 11, and 12.
([starting material]) vs time) for both 11 and 12 (Supporting
Information, SI).
We next studied the same RCM reaction with the phosphine-
free complexes 6-10 (Figure 3). Due to the slower initiation
of these catalysts, we carried out the RCM reactions at 50 °C.
Despite their decreased steric protection, complexes 6-10 were
found to be very efficient catalysts for the RCM of 18. All of
them led to >97% conversion at 1 mol % catalyst loading. The
most efficient catalysts (8 and 9) demonstrated activity com-
(29) See: Ritter, T.; Hejl, A.; Wenzel, A. G.; Funk, T. W.; Grubbs, R. H.
Organometallics 2006, 25, 5740-5745 and literature cited therein.
9
2238 J. AM. CHEM. SOC. VOL. 130, NO. 7, 2008

Ruthenium Olefin Metathesis Catalysts
A R T I C L E S
Figure 5. Log plots for catalysts 6-10 in the RCM of diethyldiallylma-
lonate (18) at 60 °C (1 mol % catalyst loading).
Figure 3. RCM of diene 18 to disubstituted cycloalkene 19 at 50 °C, using
catalysts 3, 5, and 6-10.
Figure 6. RCM of diene 20 to disubstituted cycloalkene 21 at 50 °C, using
catalysts 6-10.
Figure 4. RCM of diene 18 with catalysts 6-10 at 60 °C (1 mol % catalyst
loading).
The RCM of diethylallylmethallyl malonate (20, Figure 6)
leads to the formation of a trisubstituted cyclic olefin (21). Due
to steric effects, this reaction is more demanding than the
corresponding RCM of diethyldiallyl malonate (18). As depicted
in Figure 6, complexes 6-10 efficiently catalyze this more
challenging ring-closing. Catalysts 6-9 lead the reaction to
>96% conversion in 6.5 h, whereas complex 10 is again the
least efficient catalyst due to its prolonged induction period (73%
conversion in 6.5 h). It should be also noted that the reactivities
of catalysts 7, 8, and 9 in this RCM reaction are very similar.
Phosphine-containing catalysts 11 and 12 ring-close substrate
20 as well (SI), slightly surpassing in efficiency the first-
generation phosphine-containing catalyst 2 (2.5 mol % catalyst
loading, 0.1 M 20, 30 °C, CD2Cl2). Nevertheless, both 11 and
12 suffer from a high decomposition rate reaching a plateau of
25% and 27% maximum conversion, respectively.
The formation of tetrasubstituted double bonds via RCM is
very challenging and typically requires high catalyst loadings
and elevated reaction temperatures due to the increased steric
bulk of the substrates.11,29 In this context, complexes 8-10 do
not ring-close diethyldimethallyl malonate, even after 7 days
at 60 °C (5 mol % catalyst loading, 0.1 M substrate, C6D6),
although the catalysts are still present in the solution without
any evidence of decomposition (1H NMR spectroscopy). On
parable to the second-generation catalysts 3 and 5. As illustrated
in Figure 3, complex 10 bearing the bulkiest thiazole-2-ylidene
ligand in this catalysts family has the longest induction period.
This poor catalyst initiation upon increasing the steric bulk of
the carbene ligand is a general trend for all o-isopropoxy-styrene
catalysts.30 When 2.5 mol % catalyst loading was used at 50
°C in benzene (SI), catalysts 8 and 9 displayed >97% conver-
sion in 20 min (40 min at 1 mol % loading).
Moreover, when the RCM reaction of 18 with the phosphine-
free catalysts 6-10 was carried out at 60 °C (Figures 4 and 5),
the reaction was completed in less time. Under these conditions,
catalysts 8 and 9 led to >97% conversion in 20 min (40 min at
50 °C). Complex 10 was once again the slowest initiating
catalyst. Surprisingly, catalysts 8-10 did not show signs of
decomposition even at this elevated temperature, following
pseudo-first-order kinetics over the course of the reaction after
the end of the initial induction period (Figure 5). On the other
hand, catalysts 6 and 7, bearing the less bulky thiazole-2-ylidene
ligands, showed some curvature in their logarithmic plots,
consistent with a decrease in activity during the course of the
reaction due to decomposition.
(30) Hejl, A. H. Ph.D. Thesis, California Institute of Technology, Pasadena,
2007.
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A R T I C L E S
Vougioukalakis and Grubbs
Table 2. ROMP of Norbornene (24) Using Catalysts 6-10
a
catalyst
yield [%]
Mn
PDIa
cis/trans ratiob
6
7
8
9
10
83
77
79
74
77
45 000
41 000
53 000
32 000
70 000
3.8
4.2
4.2
4.8
4.4
45/55
42/58
44/56
43/57
36/64
a Determined by GPC (THF). bDetermined by NMR spectroscopy;
catalysts 3 and 5 afforded polymers with a 46/54 and 66/34 cis/trans ratio,
respectively.
less than 1 h, while catalysts 6 and 10 are less efficient. The
reason for the low efficiency of complex 10 is its prolonged
induction period even at 60 °C, as observed in the RCM studies.
The ROMP of highly strained molecules such as norbornene
and norbornene derivatives takes place with a significantly
higher reaction rate relative to 22.32 As shown in Table 2,
catalysts 6-10 efficiently polymerize norbornene (24) at catalyst
loadings as low as 0.2 mol %. Although the polymerization
reactions were carried out at -20 °C, the polydispersity indices
(PDIs) of the resulting polymers were rather high (3.8-4.8).
This suggests slow initiation (relative to propagation) and/or
that extensive chain transfer occurred either inter- or intramo-
lecularly. Last, all initiators afforded a predominantly trans-
olefin microstructure with catalyst 10 being the most selective
(cis/trans ratio: 36/64).
Figure 7. ROMP of 1,5-cyclooctadiene (22) using catalysts 2-5, 11, and
12.
Cross Metathesis (CM) Activity: CM is more challenging
than either RCM or ROMP, because it lacks the entropic driving
force of RCM and the ring-strain release of ROMP. Moreover,
statistically, CM reactions often lead to relatively low yields of
the desired cross-product, as well as poor E/Z cross-product
selectivity.33 In CM, the E/Z selectivity at high conversion is
governed by thermodynamic factors; namely, secondary me-
tathesis promotes isomerization of the product to the thermo-
dynamically favored E isomer. The development of catalysts
that could efficiently control E/Z selectivity in CM reactions
still represents a major challenge.
We chose to evaluate the phosphine-free thiazole-2-ylidene
catalysts in the CM of allyl benzene (26) with cis-1,4-diacetoxy-
2-butene (27, Figure 9). Apart from the heterocoupled product
(28), trans-1,4-diacetoxy-2-butene as well as both E and Z
homocoupled allylbenzene were also formed and monitored
during the course of the reaction via GC analysis. The
conversion to the heterocoupled product 28 vs time, catalyzed
by 6-10, is shown in Figure 9. Catalysts 7 and 9 demonstrated
exactly the same reactivity, while catalyst 8 proved to be slightly
more efficient affording a higher yield of the desired cross-
Figure 8. Monitoring the ROMP of 1,5-cyclooctadiene with catalysts 6-10.
the contrary, initiators 6 and 7 slowly ring-close dieth-
yldimethallyl malonate (3% and 5% conversion, respectively,
7 days, 60 °C, 5 mol % catalyst loading, 0.1 M substrate, C6D6)
simultaneously undergoing complete decomposition.
Ring-Opening Metathesis Polymerization (ROMP) Activ-
ity: The ROMP of monomers containing strained, unsaturated
rings is one of the earliest commercial applications of olefin
metathesis.1,31 We initially studied the catalytic activity of the
new thiazole-2-ylidene-bearing complexes in the ROMP of 1,5-
1
cyclooctadiene (22) by H NMR spectroscopy. Overall, the
reactivity trends for ROMP were found to be similar to those
observed for RCM. The phosphine-containing complexes (11
and 12) promote the ROMP of 22, leveling off at 61% and 38%
conversion, respectively, after 110 min at 30 °C (Figure 7). Both
catalysts initiate quickly, but their decomposition rate is also
high, as evidenced by their decreasing catalytic activity over
the course of the reaction. As illustrated in Figure 8, phosphine-
free initiators 6-10 polymerize 22 as well. Catalysts 7-9 lead
to the complete conversion of 22 to the polyalkenamer 23 in
(32) (a) Amir-Ebrahimi, V.; Corry, D. A.; Hamilton, J. G.; Thompson, J. M.;
Rooney, J. J. Macromolecules 2000, 33, 717-724. (b) Bielawski, C. W.;
Grubbs, R. H. Angew. Chem., Int. Ed. 2000, 39, 2903-2906. For
representative examples on the use of other transition metal complexes in
the ROMP of highly strained monomers, see: (c) Gilliom, L. R.; Grubbs,
R. H. J. Am. Chem. Soc. 1986, 108, 733-742. (d) Petasis, N. A.; Fu, D.
K. J. Am. Chem. Soc. 1993, 115, 7208-7214. (e) Totland, K. M.; Boyd,
T. J.; Lavoie, G. G.; Davis, W. M.; Schrock, R. R. Macromolecules 1996,
29, 6114-6125. For two review articles on living ROMP, see: (f) Schrock,
R. R. Acc. Chem. Res. 1990, 23, 158-165. (g) Bielawski, C. W.; Grubbs,
R. H. Prog. Polym. Sci. 2007, 32, 1-29.
(33) For a general model on the selectivity of CM reactions, see: Chatterjee,
A. K.; Choi, T. L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc. 2003,
125, 11360-11370.
(31) Slugovc, C. Macromol. Rapid Commun. 2004, 25, 1283-1297.
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2240 J. AM. CHEM. SOC. VOL. 130, NO. 7, 2008

Ruthenium Olefin Metathesis Catalysts
A R T I C L E S
Figure 9. Conversion to heterocoupled product 28 using catalysts 6-10.
Figure 11. Conversion of lactone 29 to the 14-membered ring-closed
product 30 using catalysts 3 and 5-10.
Figure 10. E/Z selectivity versus conversion in the CM reaction of allyl
benzene (26) with cis-1,4-diacetoxy-2-butene (27).
Figure 12. E/Z selectivity versus conversion in the macrocyclic ring-closing
reaction of 29.
product. Catalyst 10 was the least reactive catalyst in the series
due to its poor initiation. More importantly, these new catalysts
produce more Z-olefin upon increasing the bulkiness of the
N-aryl substituents of the thiazole-2-ylidene ligand, as illustrated
in the plots of the E/Z ratio of cross-product vs conversion to
cross-product (Figure 10). Complex 6 is the least Z-selective
catalyst, affording a relatively constant 6.5 E/Z ratio for a
heterocoupled product conversion up to 60%. Increasing the
bulkiness of the N-aryl group on the thiazole-2-ylidene ligand,
catalysts become more Z-selective with complex 10 being the
most selective of all, affording an E/Z ratio that is smaller than
4 for up to 50% heterocoupled product yield. The E/Z selectivity
differences among the catalysts are more pronounced at low
conversion levels, where the inherent diastereoselectivity of the
catalyst seems to determine the E/Z outcome of the reaction.
At conversions higher than 60%, the catalysts isomerize the
product to the thermodynamically favored E isomer, ultimately
reaching an E/Z ratio of about 8.34 The same trend is also
observed for catalysts 6-9 at 25 °C (catalyst 10 has a very
long induction perion at this temperature), although the selectiv-
ity differences are smaller (see SI).
Macrocyclic Ring-Closing Metathesis Activity: A variety
of macrocyclic (>seven-membered) lactones, lactams, ketones,
and ethers, some of which are alkaloids, perfume ingredients,
and antibiotics, can be efficiently synthesized via macrocyclic
ring-closing reactions of the corresponding R,ω-dienes.35 To
further exploit the potential of complexes 6-10 in olefin
metathesis, we studied their catalytic activity in the macrocyclic
ring-closing of the 14-membered lactone 29 (Figure 11).36
Initiators 7-9 were the most reactive catalysts in this family,
showing reactivity comparable to that of the second-generation
catalysts 3 and 5. Catalysts 6-10 display almost identical
stereoselectivity in this reaction, producing macrocyclic product
30 with an E/Z ratio that begins at ∼3 and finally reaches the
value of ∼6 at 85% conversion (Figure 12). Moreover, as clearly
illustrated in Figure 12, the E/Z profile of catalysts 6-10 is
(35) Review articles: (a) Fu¨rstner, A.; Langemann, K. Synthesis 1997, 792-
803. (b) Gaich, T.; Mulzer, J. Curr. Top. Med. Chem. 2005, 5, 1473-
1494. (c) Van de Weghe, P.; Eustache, J. Curr. Top. Med. Chem. 2005, 5,
1495-1519. (d) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem.,
Int. Ed. 2005, 44, 4490-4527.
(36) This macrocyclic ring-closing reaction has been performed in the past with
other ruthenium-based olefin metathesis initiators: (a) Lee, C. W.; Grubbs,
R. H. Org. Lett. 2000, 2, 2145-2147. (b) Conrad, J. C.; Eelman, M. D.;
Duarte Silva, J. A.; Monfette, S.; Parnas, H. H.; Snelgrove, J. L.; Fogg, D.
E. J. Am. Chem. Soc. 2007, 129, 1024-1025.
(34) The E/Z ratio of the first-generation catalysts 2 and 4 in the same reaction
is ∼5. Second-generation catalysts 3 and 5 give lower E/Z ratios (∼3) at
low conversion, but when the conversion increases above 60% the product
E/Z ratios increase dramatically (see ref 29).
9
J. AM. CHEM. SOC. VOL. 130, NO. 7, 2008 2241

A R T I C L E S
Vougioukalakis and Grubbs
RCM reactions. Inside a glovebox, a volumetric flask was charged with
the catalyst (0.016 mmol) and C6D6 (or CD2Cl2) was added to prepare
1.0 mL of stock solution A (0.016 M). A 0.5 mL aliquot of A was
then transferred to another 2 mL volumetric flask and diluted to 2 mL
with C6D6 (or CD2Cl2) to prepare stock solution B (0.004 M).
RCM of Diethyldiallyl Malonate (18): An NMR tube with a screw-
cap septum top was charged inside a glovebox with catalyst stock
solution B (200 µL, 0.80 µmol, 1.0 mol % or 500 µL, 2 µmol, 2.5 mol
%) and C6D6 (or CD2Cl2) (600 or 300 µL, respectively). The sample
was equilibrated at 30, 50, or 60 °C in the NMR probe before 18 (19.3
µL, 19.2 mg, 0.080 mmol, 0.1 M) was added via syringe. Data points
were collected over an appropriate period of time using the Varian
array function. The conversion to 19 was determined by comparing
the ratio of the integrals of the methylene protons in the starting material,
δ 2.83 (dt), with those in the product, δ 3.13 (s). (These are the chemical
shifts in C6D6; in CD2Cl2 the corresponding chemical shifts are δ 2.61
(dt) and δ 2.98 (s).)
RCM of Diethylallylmethallyl Malonate (20): An NMR tube with
a screw-cap septum top was charged inside a glovebox with catalyst
stock solution B (200 µL, 0.80 µmol, 1.0 mol % or 500 µL, 2 µmol,
2.5 mol %) and C6D6 (or CD2Cl2) (600 or 300 µL, respectively). The
sample was equilibrated at 30, 50, or 60 °C in the NMR probe before
20 (20.5 µL, 20.4 mg, 0.080 mmol, 0.1 M) was added via syringe.
Data points were collected over an appropriate period of time using
the Varian array function. The conversion to 21 was determined by
comparing the ratio of the integrals of the methylene protons in the
starting material, δ 2.91 (s), 2.88 (dt), with those in the product, δ
3.15 (s), 3.05 (m). (These are the chemical shifts in C6D6; in CD2Cl2,
the corresponding chemical shifts are δ 2.67 (s), 2.64 (dt) for the starting
material and δ 2.93 (s), 2.88 (m) for the product.)
ROMP Activity Tests.38 ROMP of 1,5-Cyclooctadiene (22): An
NMR tube with a screw-cap septum top was charged inside a glovebox
with a catalyst stock solution in CD2Cl2 or CDCl3 (0.004 M, 800 µL,
3.2 µmol, 0.8 mol % or 100 µL of the 0.004 M stock solution (B), 0.1
mol %, along with 700 µL of solvent). The sample was equilibrated at
30 or 60 °C in the NMR probe before 22 (49.1 µL, 43.3 mg, 0.40
mmol, 0.5 M) was added via syringe. Data points were collected over
an appropriate period of time using the Varian array function. The
conversion to 23 was determined by comparing the ratio of the integrals
of the methylene protons in the starting material, δ 2.31 (m), with those
in the product, δ 2.05 (br m), 2.00 (br m).
ROMP of Norbornene (24): Typically, 24 (47.1 mg, 0.5 mmol)
and dry, degassed CH2Cl2 (2 mL) were added in a flame-dried 4 mL
vial equipped with a screw-cap septum top, under an atmosphere of
argon. In a glovebox, the catalyst (0.002 mmol) and CH2Cl2 (1 mL)
were combined in another 4 mL vial with a screw-cap septum top and
the vial was taken out of the glovebox. Both solutions were equilibrated
at -20 °C for 5 min before 0.5 mL of the catalyst solution (0.001
mmol of catalyst, monomer/catalyst ) 500) was added to the monomer
solution via a syringe. The reaction was allowed to stir at -20 °C for
90 min under an argon atmosphere and then quenched with ethyl vinyl
ether (500 µL). The reaction was stirred at -20 °C for 10 more min
and then left to reach room temperature. This solution was added
dropwise to 50 mL of MeOH under vigorous stirring. Polynorbornene
(25) completely precipitated after 5-10 min of stirring. It was then
collected, washed with MeOH (3 × 2 mL), and dried under high
vacuum overnight, before analyzed by GPC and NMR.
completely different than that of catalysts 3 and 5 and more
similar to the stereoselectivity displayed by the first-generation
catalyst 2 in the same reaction.36a
Conclusions
A series of ruthenium-based olefin metathesis initiators,
coordinated with thiazole-2-ylidene ligands, have been synthe-
sized and completely characterized. Despite their decreased
steric protection, these complexes are competent catalysts for
ring-closing metathesis, cross metathesis, and ring-opening
metathesis polymerization. Especially the phosphine-free thia-
zole-2-ylidene-bearing catalysts are unexpectedly robust, show-
ing stability and activity comparable to those of the existing
NHC-containing ruthenium catalysts. The most stable of these
new complexes follow pseudo-first-order kinetics in the ring-
closing of diethyldiallyl malonate even at 60 °C. Increasing the
size of the ortho substituents on the N-aryl group of the thiazole-
2-ylidene ligand from H to Et leads to phosphine-free catalysts
with increased stability; however, increasing the steric bulk
further to i-Pr results in slower catalyst initiation. Unlike
previously evaluated catalysts, the steric bulk of these new
thiazole-2-ylidene-containing complexes is correlated to the
observed E/Z ratio of the cross-product in the cross metathesis
reaction of allyl benzene with cis-1,4-diacetoxy-2-butene. Thus,
decreasing the steric demand of the ortho substituents on the
N-aryl groups from i-Pr to H results in an increased E-selectivity
from ∼4 to ∼6.5.
Experimental Section
Materials and General Procedures: Unless otherwise indicated,
all compounds were purchased from Aldrich or Fisher. Catalysts 2 and
4 were obtained from Materia, Inc. Silica gel used for the purification
of organometallic complexes was obtained from TSI Scientific,
Cambridge, MA (60 Å, pH 6.5-7.0). 3-(2,6-Diisopropylphenyl)-4,5-
dimethylthiazolium chloride (14e) was prepared according to literature
methods.18,21,22 All reactions involving metal complexes were conducted
in oven-dried glassware under an argon atmosphere with anhydrous
solvents, using standard Schlenk and glovebox techniques. Anhydrous
solvents were obtained via elution through a solvent column drying
system.37 NMR chemical shifts are reported in ppm downfield from
1
Me4Si, by using the residual solvent peak as internal standard for H
and 13C and H3PO4 (δ 0.0) for 31P. Data for NMR spectra are reported
as follows: chemical shift (δ ppm), multiplicity, coupling constant (Hz),
and integration. Gas chromatography data were obtained using an
Agilent 6850 FID gas chromatograph equipped with a DB-Wax
Polyethylene Glycol capillary column (J&W Scientific). Gel permeation
chromatography (GPC) was carried out in THF on two PLgel 5 µm
mixed-B columns (Polymer Labs) connected in series with a DAWN
EOS multiangle laser light scattering (MALLS) detector and an Optilab
DSP differential refractometer (both from Wyatt Technology). No
calibration standards were used, and dn/dc values were obtained for
each injection by assuming 100% mass elution from the columns. X-ray
crystallographic structures were obtained by Larry M. Henling and Dr.
Michael W. Day of the California Institute of Technology Beckman
Institute X-ray Crystallography Laboratory. Crystallographic data have
been deposited at the CCDC, 12 Union Road, Cambridge CB2 1EZ,
U.K., and copies can be obtained on request, free of charge, by quoting
the publication citation and the deposition numbers 642800 (6), 642801
(7), 639435 (8), and 634944 (9).
CM Activity Tests.38 Cross Metathesis of Allylbenzene (26) with
cis-1,4-Diacetoxy-2-butene (27): 26 (1.00 mL, 7.55 mmol) and
tridecane (internal standard, 0.920 mL, 3.77 mmol) were combined in
a flame-dried, 4 mL vial under an atmosphere of argon. The mixture
was stirred before taking a t0 time point. The catalyst (10 µmol) and
CHCl3 (1 mL) were added in a 4 mL vial inside a glovebox. The vial
was taken out of the glovebox, and 27 (64 µL, 0.40 mmol) and the
allylbenzene/tridecane mixture (51 µL) were added simultaneously via
syringe. The reaction was allowed to stir at 25 or 60 °C. Samples for
RCM Activity Tests.38 Preparation of the Stock Solutions: Two
stock solutions can be prepared that contain enough catalyst for all
(37) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers,
F. J. Organometallics 1996, 15, 1518-1520.
(38) All reactions were performed at least in duplicate to confirm reproducibility.
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2242 J. AM. CHEM. SOC. VOL. 130, NO. 7, 2008

Ruthenium Olefin Metathesis Catalysts
A R T I C L E S
GC analysis were obtained by adding a 30 µL reaction aliquot to 500
µL of a 3M solution of ethyl vinyl ether in dichloromethane. The sample
was shaken, allowed to stand for at least 5 min, and then analyzed via
GC.
134.60, 134.30, 132.23, 132.00, 128.08, 126.55, 17.23, 12.90, 11.98.
HRMS (FAB+): calculated for C12H14NS [M]+ 204.0847, observed
204.0845.
N-Formyl-2,4,6-trimethylaniline 13c: This formanilide was pre-
pared as described for 13b. After the solvent was evaporated under
reduced pressure, the obtained yellow solid was washed with hot diethyl
ether to afford 13c as a white solid (70% yield). 1H NMR (CDCl3, 300
MHz): δ ) 8.39-8.03 (m, 1H, CHO), 7.26-6.91 (m, 2H), 6.75 (broad
s, 1H, NH), 2.29-2.21 (m, 9H); 13C{1H} NMR (CDCl3, 75 MHz): δ
) 165.48, 160.05, 137.75, 137.61, 135.37, 135.16, 130.92, 130.74,
129.53, 129.16, 21.15, 21.12, 18.84, 18.64. HRMS (FAB+): calculated
for C10H14NO [M]+ 164.1075, observed 164.1116.
3-(2,4,6-Trimethylphenyl)-4,5-dimethylthiazolium Chloride 14c:
This dimethylthiazolium chloride was prepared and purified as described
for 14a. Upon concentration of the last yellowish band from the
chromatography column, a viscous yellow oil was obtained. This was
solidified when washed under vigorous stirring with diethyl ether to
afford 14c as a tan solid (17% yield). 1H NMR (CDCl3, 300 MHz): δ
) 10.84 (s, 1H), 6.96 (s, 2H), 2.57 (s, 3H), 2.27 (s, 3H), 2.02 (s, 3H),
1.85 (s, 6H); 13C{1H} NMR (CDCl3, 75 MHz): δ ) 160.81, 142.18,
141.58, 134.95, 133.65, 132.86, 130.36, 21.35, 17.57, 13.21, 11.62.
HRMS (FAB+): calculated for C14H18NS [M]+ 232.1160, observed
232.1158.
Macrocyclic Ring-Closing Metathesis Activity Tests.38 Macro-
cyclic Ring-Closing Metathesis of Diene 29: 14-Membered lactone
29 (410 µL, 1.5 mmol) and tridecane (internal standard, 500 µL, 2.05
mmol) were combined in a flame-dried, 4 mL vial under an atmosphere
of argon. The mixture was stirred before taking a t0 time point. The
catalyst (1.5 µmol) and dry, degassed ClCH2CH2Cl (6 mL) were added
in a 20 mL vial in a glovebox. The vial was taken out of the glovebox
and equilibrated at 50 °C for 5 min under argon, and the 14-membered
lactone/tridecane mixture (18 µL) was then added via syringe. The
reaction was allowed to stir at 50 °C. Samples for GC analysis were
obtained by adding a 400 µL reaction aliquot to 100 µL of a 3M solution
of ethyl vinyl ether in dichloromethane. The sample was shaken,
allowed to stand for at least 5 min, and then analyzed via GC.
3-Phenyl-4,5-dimethylthiazolium chloride 14a:22 A mixture of
N-formyl-aniline (13a) (3.634 g, 30 mmol) and phosphorus pentasulfide
(1.351 g, 3.04 mmol) in dry 1,4-dioxane (4 mL) was stirred at room
temperature for 15 min under an argon atmosphere. 3-Chloro-2-
butanone (2.131 g, 20 mmol) was added, and the resulting slurry was
heated at 100 °C. The reaction mixture was refluxed for 50 min, initially
becoming clear yellow and finally deep red. After cooling at room
temperature, the crude mixture was diluted with H2O (20 mL). Na2-
CO3 was added to the reaction mixture until pH ≈ 7. The solvent was
evaporated under reduced pressure, and the resulting solid was
suspended in CH2Cl2 and purified by column chromatography eluting
with EtOH/CH2Cl2 (15/85). Upon concentration of the last yellowish
band, a viscous orange oil was obtained. This was solidified when
washed under vigorous stirring with diethyl ether (3 × 2 mL) to afford
14a as a light pink solid (770 mg, 11%). 1H NMR (CD2Cl2, 300
MHz): δ ) 11.13 (s, 1H), 7.67-7.60 (m, 3H), 7.53-7.49 (m, 2H),
2.57 (s, 3H), 2.23 (s, 3H); 13C{1H} NMR (CD2Cl2, 75 MHz): δ )
161.03, 142.08, 141.75, 137.19, 132.10, 130.84, 126.34, 13.10, 12.86.
HRMS (FAB+): calculated for C11H12NS [M]+ 190.0690, observed
190.0693.
N-Formyl-2,6-diethylaniline 13d: This formanilide was prepared
as described for 13b. After the solvent was evaporated under reduced
pressure, the remaining yellow solid was washed with hot diethyl ether
to afford 13d as a white solid (74% yield). 1H NMR (CDCl3, 300
MHz): δ ) 8.15-8.02 (m, 1H, CHO), 7.86 (broad s, 1H, NH), 7.25-
7.06 (m, 3H), 2.65 (q, J ) 7 Hz, 2H), 2.53 (q, J ) 7 Hz, 2H), 1.20 (t,
J ) 7 Hz, 3H), 1.14 (t, J ) 7 Hz, 3H); 13C{1H} NMR (CDCl3, 75
MHz): δ ) 165.97, 161.00, 142.13, 141.52, 132.15, 131.66, 128.65,
128.37, 127.09, 126.49, 25.18, 25.04, 15.00, 14.62. HRMS (EI+):
calculated for C11H15NO [M]+ 177.1154, observed 177.1159.
3-(2,6-Diethylphenyl)-4,5-dimethylthiazolium Chloride 14d:22
A
mixture of 13d (3.545 g, 20 mmol) and phosphorus pentasulfide (0.900
g, 2.02 mmol) in dry 1,4-dioxane (5 mL) was stirred at room
temperature for 15 min under an argon atmosphere. 3-Chloro-2-
butanone (1.422 g, 20 mmol) was added, and the resulting slurry was
heated at 100 °C. The reaction mixture was refluxed for 50 min, initially
becoming clear yellow and finally deep red. After cooling at room
temperature, the crude mixture was diluted with H2O (20 mL), and
Na2CO3 was added to the reaction mixture until pH ≈ 7. The solvent
was evaporated under reduced pressure, and the resulting solid was
suspended in CH2Cl2 and purified by column chromatography eluting
with EtOH/CH2Cl2 (15/85). Upon concentration of the last band, a
viscous brownish oil was obtained. This was solidified when washed
under vigorous stirring with diethyl ether (3 × 2 mL) to afford 14d as
N-Formyl-2-methylaniline 13b:21 A mixture of formic acid (14.361
g, 0.312 mol) and acetic anhydride (12.659 g, 0.124 mol) was stirred
at room temperature for 1 h under an argon atmosphere. This mixture
was added to a solution of 2-methylaniline (10.710 g, 0.1 mol) in dry
dichloromethane (60 mL) at such a rate that the temperature of the
reaction mixture was kept between 5 and 10 °C. The reaction was stirred
at room temperature for 16 h and then refluxed for 4 h. The solvent
was evaporated under reduced pressure, and the residue was dissolved
in CHCl3 (200 mL) and washed with a saturated aqueous NaHCO3
solution (3 × 200 mL) and water (200 mL). The organic layer was
dried over Na2SO4, and the solvent was evaporated under reduced
pressure. The remaining yellow solid was washed with a mixture of
hexanes/diethyl ether (2 × 10 mL) and then with hexanes (3 × 5 mL)
1
a tan solid (560 mg, 10%). H NMR (CDCl3, 300 MHz): δ ) 10.97
(s, 1H), 7.52 (t, J ) 8 Hz, 1H), 7.30 (d, J ) 8 Hz, 2H), 2.63 (s, 3H),
2.16 (q, J ) 8 Hz, 4H), 2.06 (s, 3H), 1.14 (t, J ) 8 Hz, 6H); 13C{1H}
NMR (CDCl3, 75 MHz): δ ) 161.92, 141.63, 139.62, 135.04, 134.20,
132.30, 127.65, 23.97, 14.18, 13.16, 11.82. HRMS (FAB+): calculated
for C15H20NS [M]+ 246.1316, observed 246.1326.
1
to afford 13b as a white solid (9.70 g, 72%). H NMR (CDCl3, 300
MHz): δ ) 9.03-8.18 (m, 2H, CHO, NH), 7.77-7.03 (m, 4H), 2.30-
2.22 (m, 3H); 13C{1H} NMR (CDCl3, 75 MHz): δ ) 164.41, 160.32,
135.50, 134.99, 131.45, 130.82, 130.50, 129.87, 127.25, 126.80, 126.34,
125.84, 123.75, 121.32, 18.05, 17.99. HRMS (FAB+): calculated for
C8H10NO [M]+ 136.0762, observed 136.0783.
[RuCl2 (3-Phenyl-4,5-dimethylthiazol-2-ylidene) (dCH-o-iPrOs
Ph)] 6: In a glovebox, 3-phenyl-4,5-dimethylthiazolium chloride (14a)
(113.0 mg, 0.50 mmol, 1 equiv), silver(I) oxide (58.0 mg, 0.25 mmol,
0.5 equiv), and 4 Å molecular sieves (113 mg) were suspended in CH2-
Cl2 (7 mL) in the dark. The reaction mixture was stirred at room
temperature for 1 h. Complex 4 (270 mg, 0.45 mmol, 0.9 equiv) was
added as a solid in one portion, and the reaction flask was taken out of
the glovebox and stirred under a nitrogen atmosphere at room
temperature for 1.5 h in the dark. The solvent was removed in vacuo,
and the remaining solid was dissolved in a minimum amount of C6H6
and poured onto a column packed with TSI Scientific silica gel. The
complex was eluted with pentanes/diethyl ether (1/1) as a brown-green
band. The solvent was removed in vacuo, and the obtained solid was
3-(2-Methylphenyl)-4,5-dimethylthiazolium Chloride 14b: This
dimethylthiazolium chloride was prepared and purified as described
for 14a. Upon concentration of the last yellowish band from the
chromatography column, a viscous orange oil was obtained. This was
solidified when washed under vigorous stirring with diethyl ether to
1
afford 14b as a tan solid (17% yield). H NMR (CD2Cl2, 300 MHz):
δ ) 11.09 (s, 1H), 7.53-7.31 (m, 4H), 2.57 (s, 3H), 2.08 (s, 3H), 2.04
(s, 3H); 13C{1H} NMR (CD2Cl2, 75 MHz): δ ) 160.77, 142.05, 136.10,
9
J. AM. CHEM. SOC. VOL. 130, NO. 7, 2008 2243

A R T I C L E S
Vougioukalakis and Grubbs
transferred in a glovebox, dissolved in the minimum amount of benzene,
and lyophilized to afford the desired complex as a brown-yellow solid
(75 mg, 0.147 mmol, 32% yield). The complex is stable in air in the
solid state and soluble in CH2Cl2, CHCl3, benzene, toluene, and THF.
Crystals suitable for X-ray crystallography were grown at room
temperature by slow diffusion of hexanes into a solution of 6 in
benzene.1H NMR (CD2Cl2, 500 MHz): δ ) 17.93 (s, 1H), 7.90-7.88
(m, 2H), 7.79-7.77 (m, 1H), 7.70-7.58 (m, 4H), 7.15-7.08 (m, 2H),
5.14 (septet, J ) 6 Hz, 1H), 2.42 (s, 3H), 2.12 (s, 3H), 1.52 (d, J ) 6
Hz, 6H); 13C{1H} NMR (CD2Cl2, 125 MHz): δ ) 287.26, 215.05,
154.90, 143.81, 143.80, 142.49, 139.96, 130.36, 129.71, 129.57, 129.18,
122.95, 122.26, 113.68, 75.67, 21.72, 12.97, 12.71. HRMS (FAB+):
calculated for C21H23Cl2NORuS [M]+ 508.9921, observed 508.9900.
ether (1/1) as a brown band. The solvent was removed in vacuo, and
the obtained solid was transferred in a glovebox, dissolved in the
minimum amount of benzene, and lyophilized to afford the desired
complex as a brown solid (74 mg, 0.131 mmol, 58% yield). The
complex is stable in air in the solid state and soluble in CH2Cl2, CHCl3,
benzene, toluene, and THF. Crystals suitable for X-ray crystallography
were grown at room temperature by slow diffusion of hexanes into a
solution of 9 in benzene. 1H NMR (CD2Cl2, 500 MHz): δ ) 17.27 (s,
1H), 7.66-7.62 (m, 2H), 7.54 (t, J ) 8 Hz, 1H), 7.34 (d, J ) 8 Hz,
2H), 7.11-7.06 (m, 2H), 5.16 (septet, J ) 6 Hz, 1H), 2.62 (m, 2H),
2.43 (s, 3H), 2.24 (m, 2H), 1.88 (s, 3H), 1.59 (d, J ) 6 Hz, 6H), 1.17
(t, J ) 7 Hz, 6H); 13C{1H} NMR (CD2Cl2, 125 MHz): δ ) 282.90,
210.53, 154.52, 143.77, 142.20, 140.93, 139.54, 131.26, 130.09, 130.00,
125.80, 122.79, 122.42, 113.65, 75.91, 31.52, 27.39, 27.30, 26.08, 24.06,
21.76, 13.23, 12.71, 12.28. HRMS (FAB+): calculated for C25H30Cl2-
NORuS [M]+ 564.0469, observed 564.0461.
[RuCl2 (3-(2-Methylphenyl)-4,5-dimethylthiazol-2-ylidene) (d
CH-o-iPrOsPh)] 7: This ruthenium complex was prepared and
purified as described for complex 6 (53% yield). Crystals suitable for
X-ray crystallography were grown at room temperature by slow
[RuCl2 (3-(2,6-Diisopropylphenyl)-4,5-dimethylthiazol-2-ylidene)
(dCH-o-iPrOsPh)] 10: 3-(2,6-Diisopropylphenyl)-4,5-dimethylthi-
azolium chloride (14e) (190.8 mg, 0.616 mmol, 2.2 equiv) was stirred
with an equimolar quantity of KHMDS (122.8 mg, 0.616 mmol) in
benzene (15 mL) inside a glovebox at room temperature for 30 min.
Catalyst 4 (168.2 mg, 0.28 mmol, 1.0 equiv) was added as a solid in
one portion, and the reaction flask was taken out of the glovebox and
stirred under a nitrogen atmosphere at room temperature for 1 h. The
solution was concentrated to 2 mL in vacuo and poured onto a column
packed with TSI Scientific silica gel. The complex was eluted with
hexanes/diethyl ether (1/1) as a brown band. The solvent was removed
in vacuo, and the obtained solid was transferred in a glovebox, dissolved
in the minimum amount of benzene, and lyophilized to afford the
desired complex as a brown solid (66 mg, 0.11 mmol, 40% yield).
The complex is stable in air in the solid state and soluble in CH2Cl2,
1
diffusion of hexanes into a solution of 7 in benzene. H NMR (CD2-
Cl2, 500 MHz): δ ) 17.92 (s, 1H), 8.09-8.07 (m, 1H), 7.79-7.77
(m, 1H), 7.70-7.67 (m, 1H), 7.53-7.49 (m, 2H), 7.44-7.42 (m, 1H),
7.15-7.07 (m, 2H), 5.12 (septet, J ) 6 Hz, 1H), 2.42 (s, 3H), 2.16 (s,
3H), 2.01 (s, 3H), 1.53 (d, J ) 6 Hz, 3H), 1.44 (d, J ) 6 Hz, 3H);
13C{1H} NMR (CD2Cl2, 125 MHz): δ ) 287.59, 215.39, 155.27,
144.32, 144.30, 141.81, 140.49, 138.46, 130.70, 130.04, 129.90, 129.52,
123.29, 122.59, 114.02, 76.01, 22.13, 22.07, 19.13, 13.17, 12.36. HRMS
(FAB+): calculated for C22H25Cl2NORuS [M]+ 523.0078, observed
523.0069.
[RuCl2 (3-(2,4,6-Trimethylphenyl)-4,5-dimethylthiazol-2-ylidene)
(dCH-o-iPrOsPh)] 8: In a glovebox, 3-(2,4,6-trimethylphenyl)-4,5-
dimethylthiazolium chloride (14c) (93.8 mg, 0.35 mmol, 1 equiv),
silver(I) oxide (40.6 mg, 0.175 mmol, 0.5 equiv), and 4 Å molecular
sieves (95 mg) were suspended in CH2Cl2 (5 mL) in the dark. The
reaction mixture was stirred at room temperature for 1 h. Catalyst 4
(189 mg, 0.315 mmol, 0.9 equiv) was added as a solid in one portion,
and the reaction flask was taken out of the glovebox and stirred under
a nitrogen atmosphere at room temperature for 1 h in the dark. The
solvent was removed in vacuo, and the remaining solid was dissolved
in a minimum amount of C6H6 and poured onto a column packed with
TSI Scientific silica gel. The complex was eluted with pentanes/diethyl
ether (1/1) as a brown band. The solvent was removed in vacuo, and
the obtained solid was transferred in a glovebox, dissolved in the
minimum amount of benzene, and lyophilized to afford the desired
complex as a brown solid (93 mg, 0.168 mmol, 54% yield). The
complex is stable in air in the solid state and soluble in CH2Cl2, CHCl3,
benzene, toluene, and THF. Crystals suitable for X-ray crystallography
were grown at room temperature by slow diffusion of hexanes into a
solution of 8 in benzene. 1H NMR (CD2Cl2, 500 MHz): δ ) 17.27 (s,
1H), 7.67-7.59 (m, 2H), 7.12-7.07 (m, 4H), 5.17 (septet, J ) 6 Hz,
1H), 2.43 (s, 6H), 2.09 (s, 6H), 1.87 (s, 3H), 1.61 (d, J ) 6 Hz, 6H);
13C{1H} NMR (CD2Cl2, 125 MHz): δ ) 284.03, 211.33, 154.36,
143.92, 140.58, 139.78, 138.08, 137.00, 130.82, 130.10, 129.31, 122.81,
122.43, 113.62, 75.93, 21.74, 21.19, 18.71, 12.69, 11.90. HRMS
(FAB+): calculated for C24H29Cl2NORuS [M]+ 551.0391, observed
551.0382.
1
CHCl3, benzene, toluene, and THF. H NMR (CD2Cl2, 500 MHz): δ
) 16.60 (s, 1H), 7.63-7.57 (m, 2H), 7.38 (d, J ) 8 Hz, 2H), 7.07-
7.02 (m, 3H), 5.19 (septet, J ) 6 Hz, 1H), 2.50 (septet, J ) 7 Hz, 2H),
2.42 (s, 3H), 1.91 (s, 3H), 1.70 (d, J ) 6 Hz, 6H), 1.12 (d, J ) 7 Hz,
6H), 1.03 (d, J ) 7 Hz, 6H); 13C{1H} NMR (CD2Cl2, 125 MHz):
280.83, 209.03, 162.87, 154.15, 146.64, 143.30, 141.88, 138.53, 130.42,
129.81, 124.75, 122.63, 122.29, 113.50, 75.93, 28.41, 24.46, 24.12,
22.02, 12.99, 12.58. HRMS (FAB+) calculated for C27H35NOCl2RuS
[M]+ 593.0860, observed 593.0875.
[RuCl2 (3-(2,4,6-Trimethylphenyl)-4,5-dimethylthiazol-2-ylidene)
(dCHsPh) (PCy3)] 11: In a glovebox, 3-(2,4,6-trimethylphenyl)-4,5-
dimethylthiazolium chloride (14c) (134 mg, 0.5 mmol, 1 equiv), silver-
(I) oxide (58 mg, 0.25 mmol, 0.5 equiv), and 4 Å molecular sieves
(135 mg) were suspended in CH2Cl2 (2.5 mL) in the dark. The reaction
mixture was stirred at room temperature for 1 h. Catalyst 2 (370 mg,
0.45 mmol, 0.9 equiv) was added as a solid in one portion, and the
reaction flask was taken out of the glovebox and stirred under a nitrogen
atmosphere at room temperature for 30 min in the dark. The solvent
was removed in vacuo, and the remaining solid was dissolved in a
minimum amount of C6H6 and poured onto a column packed with TSI
Scientific silica gel. The complex was eluted with diethyl ether/pentanes
(15/85) as a green band. The solvent was removed in vacuo, and the
obtained solid was transferred in a glovebox, dissolved in the minimum
amount of benzene, and lyophilized to afford the desired complex as
a brown solid (105 mg, 0.136 mmol, 30% yield). The complex is stable
in air in the solid state and soluble in CH2Cl2, CHCl3, benzene, toluene,
[RuCl2 (3-(2,6-Diethylphenyl)-4,5-dimethylthiazol-2-ylidene)
(dCH-o-iPrOsPh)] 9: In a glovebox, 3-(2,6-diethylphenyl)-4,5-
dimethylthiazolium chloride (14d) (70.5 mg, 0.25 mmol, 1 equiv),
silver(I) oxide (29.0 mg, 0.125 mmol, 0.5 equiv), and 4 Å molecular
sieves (71 mg) were suspended in CH2Cl2 (3.5 mL) in the dark. The
reaction mixture was stirred at room temperature for 1 h. Catalyst 4
(135 mg, 0.225 mmol, 0.9 equiv) was added as a solid in one portion,
and the reaction flask was taken out of the glovebox and stirred under
a nitrogen atmosphere at room temperature for 16 h in the dark. The
solvent was removed in vacuo, and the remaining solid was dissolved
in a minimum amount of C6H6 and poured onto a column packed with
TSI Scientific silica gel. The complex was eluted with pentanes/diethyl
1
and THF. H NMR (CD2Cl2, 500 MHz): δ ) 19.61 (d, J ) 6 Hz,
1H), 8.16 (d, J ) 8 Hz, 2H), 7.59 (t, J ) 8 Hz, 1H), 7.29 (t, J ) 8 Hz,
2H), 6.84 (s, 2H), 2.34-2.24 (m, 9H), 2.11 (s, 6H), 1.77 (s, 3H), 1.71-
1.12 (m, 30H); 13C{1H} NMR (CD2Cl2, 125 MHz): δ ) 299.80, 220.39,
152.21, 140.31, 139.14, 137.94, 136.21, 131.24, 129.71, 129.46, 128.44,
107.27, 32.53, 32.40, 29.96, 28.08, 28.00, 27.21, 26.66, 21.08, 18.88,
12.35, 11.67; 31P{1H} NMR (CD2Cl2, 202 MHz) δ ) 30.96. HRMS
(FAB+): calculated for C39H56Cl2NPSRu [M]+ 773.2292, observed
773.2316.
9
2244 J. AM. CHEM. SOC. VOL. 130, NO. 7, 2008

Ruthenium Olefin Metathesis Catalysts
A R T I C L E S
[RuCl2 (3-(2,6-Diethylphenyl)-4,5-dimethylthiazol-2-ylidene) (d
CHsPh) (PCy3)] 12: In a glovebox, 3-(2,6-diethylphenyl)-4,5-dim-
ethylthiazolium chloride (14d) (70.5 mg, 0.25 mmol, 1 equiv), silver(I)
oxide (29.0 mg, 0.125 mmol, 0.5 equiv), and 4 Å molecular sieves (71
mg) were suspended in CH2Cl2 (3.5 mL) in the dark. The reaction
mixture was stirred at room temperature for 1 h. Catalyst 2 (185 mg,
0.225 mmol, 0.9 equiv) was added as a solid in one portion, and the
reaction flask was taken out of the glovebox and stirred under a nitrogen
atmosphere at room temperature for 1.5 h in the dark. The solvent was
removed in vacuo, and the remaining solid was dissolved in a minimum
amount of C6H6 and poured onto a column packed with TSI Scientific
silica gel. The complex was eluted with diethyl ether/pentanes (15/85)
as a brown band. The solvent was removed in vacuo, and the obtained
solid was transferred in a glovebox, dissolved in the minimum amount
of benzene, and lyophilized to afford the desired complex as a brown
solid (72 mg, 0.091 mmol, 41% yield). The complex is stable in air in
the solid state and soluble in CH2Cl2, CHCl3, benzene, toluene, and
12.74, 12.35, 12.03; 31P{1H} NMR (CD2Cl2, 202 MHz) δ ) 29.38.
HRMS (FAB+): calculated for C40H58RuNPSCl2 [M]+ 787.2449,
observed 787.2460.
Acknowledgment. This research was supported in part by
the National Institutes of Health and by a Marie Curie
International Fellowship to G.C.V. within the 6th European
Community Framework Programme. The authors would like
to thank Larry M. Henling and Dr. Michael W. Day for the
X-ray crystallographic analyses, Dr. Mona Shahgholi for
performing the mass spectrometric analyses, and John B. Matson
for assistance with the GPC analyses. Materia Inc. is also
acknowledged for providing generous gifts of catalysts 2 and
4.
Supporting Information Available: 1H, 13C, and 31P NMR
spectra of catalysts 6-12. Text, tables, and figures giving details
of the X-ray analysis of catalysts 6-9; crystal data are also
available as CIF files. GPC chromatograms for the ROMP of
norbornene with catalysts 6-10. Plots with additional catalytic
evaluation data for 6-12. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
THF. H NMR (CD2Cl2, 500 MHz): δ ) 19.67 (d, J ) 7 Hz, 1H),
8.16-8.14 (m, 2H), 7.60 (t, J ) 7 Hz, 1H), 7.36-7.27 (m, 3H), 7.19-
7.17 (m, 2H), 2.92 (m, 2H), 2.33-2.22 (m, 6H), 2.19-2.07 (m, 2H),
1.80 (s, 3H), 1.67-1.09 (m, 36H); 13C{1H} NMR (CD2Cl2, 125
MHz): δ ) 301.65, 219.36, 152.36, 141.37, 140.42, 140.39, 139.31,
131.28, 129.82, 129.78, 128.88, 128.52, 127.84, 126.65, 125.58, 32.53,
32.41, 31.16, 29.90, 28.08, 28.00, 27.63, 27.59, 26.65, 26.40, 24.19,
JA075849V
9
J. AM. CHEM. SOC. VOL. 130, NO. 7, 2008 2245