Improved one-pot synthesis of second-generation ruthenium olefin metathesis catalysts

Article abstract of DOI:10.1021/om0109511

One-pot synthesis of second-generation ruthenium olefin metathesis catalysts was discussed. These reactions were used to form C-C bonds. Results showed that imidazolium salt SIMes·HCL affords a higher reaction yield than SIMes·HBF₄.

Full text of DOI:10.1021/om0109511

442
Organometallics 2002, 21, 442-444
Im p r oved On e-P ot Syn th esis of Secon d -Gen er a tion
Ru th en iu m Olefin Meta th esis Ca ta lysts
Laleh J afarpour, Anna C. Hillier, and Steven P. Nolan*
Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148
Received November 2, 2001
Summary: An improved one-pot synthesis of olefin me-
tathesis catalysts (PCy3)(L)RudCHPhCl2 (L ) N-het-
erocyclic nucleophilic carbene: IMes, 3; SIMes, 4) em-
ploys potassium tert-amylate to deprotonate the imidazol-
ium salt ligand precursor. Both of the reaction steps are
carried out using a one-pot protocol in hexane with
commercially available reagents under mild conditions,
permitting the isolation of 3 and 4 by simple filtration.
droimidazol-2-ylidene, SIMes) N-heterocyclic nucleo-
philic carbene bearing N-mesityl substituents, have
recently been reported. These complexes possess greater
thermal stability than the parent complex 26 and exhibit
activity comparable to that of the most active early
transition metal systems while retaining the functional
group tolerance of complex 2. Complexes 3 and 4 have
been successfully employed in a broad range of olefin
metathesis reactions ranging from ring-closing meta-
thesis (RCM)7 to ring-opening metathesis polymeriza-
tion (ROMP)8 and cross-metathesis.9
In tr od u ction
Olefin metathesis has become a powerful assembly
strategy and a widely used synthetic tool in the forma-
tion of C-C bonds.1 This reawakened interest in olefin
metathesis processes during the past decade is largely
attributable to the discovery of highly active, well-
defined molybdenum and ruthenium alkylidene cata-
lysts 12 and 2.3 Although the ruthenium complex 2
(“Grubbs’ catalyst”) possesses significant advantages
over molybdenum complex 1 in terms of stability and
ease of storage and handling, complex 1 displays higher
reactivity toward a broad range of sterically and elec-
tronically varied substrates. However, neither of these
complexes displays significant tolerance to thermal
treatment.1
Resu lts a n d Discu ssion
The first preparations of complexes 3 and 4 employed
the isolated free (by deprotonation of the imidazolium
(4) (a) Huang, J .; Stevens, E. D.; Nolan, S. P.; Petersen, J . L. J . Am.
Chem. Soc. 1999, 121, 2674-2678. (b) Scholl, M.; Trnka, T. M.; Morgan,
J . P.; Grubbs, R. H. Tetrahedron Lett. 1999, 40, 2247-2250. (c)
Weskamp, T.; Kohl, F. J .; Hieringer, W.; Gleich, D.; Herrmann, W. A.
Angew. Chem., Int. Ed. 1999, 38, 2416-2419.
(5) Scholl, M.; Ding, S. Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1,
953-956.
(6) Huang, J .; Schanz, H. J .; Stevens, E. D.; Nolan, S. P. Organo-
metallics 1999, 18, 5375-5380.
(7) (a) Heck, M.-P.; Baylon, C.; Nolan, S. P.; Mioskowski, C. Org.
Lett. 2001, 3, 1989-1991. (b) Boyer, F.-D.; Hanna, I.; Nolan, S. P. J .
Org. Chem. 2001, 66, 4094-4096. (c) Wagner, J .; Martin Cabrejas, L.
M.; Grossmith, C. E.; Papageorgiou, C.; Senia, F.; Wagner, D.; France,
J .; Nolan, S. P. J . Org. Chem. 2000, 65, 9255-9260. (d) Fu¨rstner, A.;
Thiel, O. R.; Ackermann, L.; Schanz, H.-J .; Nolan, S. P. J . Org. Chem.
2000, 65, 2204-2207. (e) Briot, A.; Bujard, M.; Gouverneur, V.; Nolan,
S. P.; Mioskowski, C. Org. Lett. 2000, 2, 1517-1519. (f) J orgensen,
M.; Iversen, E. H.; Paulsen, A. L.; Madsen, R. J . Org. Chem. 2001, 66,
4630-4634. (g) Hyldtoft, L.; Madsen, R. J . Am. Chem. Soc. 2000, 122,
8444-8452. (h) Fu¨rstner, A.; Thiel, O. R.; Kindler, N.; Bartkowska,
B. J . Org. Chem. 2000, 65, 7990-7995. (i) Fu¨rstner, A.; Thiel, O. R.;
Ackermann, L. Org. Lett. 2001, 3, 449-451. (j) Fu¨rstner, A.; Thiel, O.
R.; Blanda, G. Org. Lett. 2000, 2, 3731-3734. (k) Benningshof, J . C.
J .; Blaauw, R. H.; van Ginkel, A. E.; Rutjes, F. P. J . T.; Fraanje, J .;
Goubitz, K.; Schenk, H.; Hiemstra, H. Chem. Commun. 2000, 1465-
1466.
Second-generation ruthenium benzylidene complexes
34 and 4,5 where one phosphine in complex 2 has been
replaced by an unsaturated (1,3-dimesitylimidazol-2-
ylidene, IMes) or saturated (1,3-dimesityl-4,5-dihy-
* Corresponding author. E-mail: snolan@uno.edu. Fax: (504) 280
6860.
(1) For recent reviews on olefin metathesis see: (a) Trnka, T. M.;
Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18-29. (b) Grubbs, R. H.;
Chang, S. Tetrahedron 1998, 54, 4413-4450, and references therein.
(c) Ivin, K. J . Mol. Catal. A: Chem. 1998, 133, 1-16. (d) Randall, M.
L.; Snapper, M. L. J . Mol. Catal. A: Chem. 1998, 133, 29-40. (e) Ivin,
K.; Mol. J . C. Olefin Metathesis and Metathesis Polymerization;
Academic Press: London, 1997.
(8) (a) Hamilton, J . G.; Frenzel, U.; Kohl, F. J .; Weskamp, T.;
Rooney, J . J .; Herrmann, W. A.; Nuyken, O. J . Organomet. Chem. 2000,
606, 8-12. (b) Bielawski, C. W.; Grubbs, R. H. Angew. Chem., Int. Ed.
2000, 39, 2903-2906.
(2) (a) Schrock, R. R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .;
Dimare, M.; O’Regan, M. J . Am. Chem. Soc. 1990, 112, 3875-3886.
(b) Bazan, G. C.; Khosravi, E.; Schrock, R. R.; Reast, W. J .; Gibson, V.
C.; O’Regan, M. B.; Thomas, J . K.; Davis, W. M. J . Am. Chem. Soc.
1990, 112, 8378-8387. (c) Bazan, G. C.; Oskam, J . H.; Cho, H. N.;
Park, L. Y.; Schrock, R. R. J . Am. Chem. Soc. 1991, 113, 6899-6907.
(3) (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.
(9) (a) Choi, T.-L.; Chatterjee, A. K.; Grubbs, R. H. Angew. Chem.,
Int. Ed. 2001, 40, 1277-1279. (b) Kitamura, T.; Sato, Y.; Mori, M.
Chem. Commun. 2001, 1258-1259. (c) Smulik, J . A.; Diver, S. T. Org.
Lett. 2000, 2, 2271-2274. (d) Ahmed, M.; Arnauld, T.; Barrett, A. G.
M.; Braddock, D. C.; Flack, K.; Procopiou, P. A. Org. Lett. 2000, 2,
551-553. (e) Stragies, R.; Voigtmann, U.; Blechert, S. Tetrahedron Lett.
2000, 41, 5465-5468. (f) Chatterjee, A. K.; Morgan, J . P.; Scholl, M.;
Grubbs, R. H. J . Am. Chem. Soc. 2000, 122, 3783-3784. (g) Chatterjee,
A. K.; Grubbs, R. H. Org. Lett. 1999, 1, 1751-1753.
10.1021/om0109511 CCC: $22.00 © 2002 American Chemical Society
Publication on Web 12/21/2001

Notes
Organometallics, Vol. 21, No. 2, 2002 443
Sch em e 1. Syn th eses of Ru th en iu m Com p lexes
3 a n d 4
salt) carbene to replace one phosphine ligand in 2.
Subsequently, to avoid the independent isolation of the
air- and moisture-sensitive carbene ligands, a one-pot
synthetic procedure for 3 was developed in which the
imidazolium salt (nucleophilic carbene precursor) is
deprotonated in situ with a strong base such as KOBut
in a nonpolar solvent.10 However, the insolubility of
KOBut in hexane called for longer reaction times and
heating the reaction mixture. This resulted in lower
than quantitative yields. In efforts to improve the yields
of this reaction, we noted that the purity of commercially
obtained KOBut left something to be desired. Purifica-
tion by sublimation (twice) improved reaction yields
somewhat. The remaining issue was the thermal treat-
ment of the reaction mixtures in view of the poor
solubility of KOBut in hexane. This was of some concern
since the commercially available ruthenium complex 2
is also known to react with excess KOBut to afford four-
coordinate complex 5 upon extensive heating. Complex
5 proved to be inactive in the RCM of diethyl diallyl-
malonate (the standard test for catalytic activity in
olefin metathesis).11
precursor, employing essentially the same reaction
protocol, with two variations. The first was the reaction
time: in a small-scale preparation, following initial de-
protonation of SIMes‚HBF4 at room temperature and
addition of 2, 2 h of stirring at 60 °C was sufficient for
the reaction to be complete. The second difference was
that an additional purification step was necessary,
namely, extraction of the filtered and washed product
into benzene, owing to the lesser solubility of KBF4 in
methanol. In all cases the obtained products were pure
Similarly, the use of prolonged reaction times at
elevated temperature in the one-pot preparation of 3
and 4 has been observed to yield products displaying
lower RCM activity. This is believed to be due to the
formation of inactive ruthenium alkoxide species.12
An alternative one-pot synthesis of 45 also employs
KOBut as base. This method involves the use of solvents
such as THF and benzene to render the starting
material soluble. The workup of the reaction mixture
consequently consists of the removal of solvents under
high vacuum. We therefore sought an alternative, more
soluble base for the ligand deprotonation step, which
would permit the use of mild reaction conditions while
maintaining the advantageous use of hexane as solvent.
Potassium tert-amylate (KOC(CH3)2CH2CH3) seemed to
be an ideal choice. It is somewhat more soluble than
KOBut in hexane but retains strongly basic character,
ensuring the complete conversion of the imidazolium
salt to the free carbene in a much shorter time. The
procedure employed is shown in Scheme 1. Reaction
between KOC(CH3)2CH2CH3 and IMes‚HCl or SIMes‚
HCl in hexane at room temperature afforded a slightly
turbid, pale yellow solution. After 1 h of stirring,
addition of 2 followed by stirring at room temperature
overnight (12 h for IMes‚HCl and formation of 3) or at
50 °C for 5 h followed by 12 h at room temperature (for
SIMes‚HCl and formation of 4) afforded a pink-brown
precipitate. This precipitate could be isolated by filtra-
tion on a collection frit, washed with methanol, and
dried in vacuo to afford good yields of complex 3 or 4.
Alternatively, SIMes‚HBF4 could be employed as ligand
1
by H and 31P NMR spectroscopies and displayed the
expected activity in the RCM of diethyl diallylmalonate.
The reaction was found to be equally successful in both
large- (20 g) and small-scale (200 mg) procedures, giving
product yields of 92% for 3 and 77% (SIMes‚HCl) or 67%
(SIMes‚HBF4) for 4.
In conclusion, an improved protocol for the prepara-
tion of second-generation olefin metathesis catalysts has
been developed. The imidazolium salt SIMes‚HCl af-
fords a higher reaction yield than SIMes‚HBF4. This is
believed to be due to the more facile deprotonation of
the imidazolium salt with the chloride counterion, borne
out by independent deprotonation reactions in NMR
experiments. This one-pot procedure makes use of
hexane as solvent. Since the products 3 and 4 are
insoluble in hexane, a simple filtration followed by a
methanol wash affords the pure product in good yield.
Exp er im en ta l Section
Gen er a l Con sid er a tion s. All reactions were carried out
under an atmosphere of dry argon. IMes‚HCl is available from
Strem Chemicals. SIMes‚HCl was synthesized following the
literature procedure.13 SIMes‚HBF4 was prepared by dissolving
SIMes‚HCl in water and adding aqueous HBF4 (50% by weight
from J . T. Baker Co.) followed by filtration and drying of the
resulting white precipitate overnight under dynamic vacuum.
Potassium tert-amylate in toluene (25 wt % solution) was
(10) J afarpour, L.; Nolan, S. P. Organometallics 2000, 19, 2055-
2057.
(11) Sanford, M. S.; Henling, L. M.; Day, M. W.; Grubbs, R. H.
Angew. Chem., Int. Ed. 2000, 39, 3451-3453.
(12) J afarpour, L.: Nolan, S. P. Unpublished observations.
(13) Viciu, M. S.; Grasa, G. A.; Nolan, S. P. Organometallics 2001,
20, 3607-3612.

444 Organometallics, Vol. 21, No. 2, 2002
Notes
purchased from Callery Chemical Co., and the solvent was
removed in vacuo to afford a waxy, cream-white solid. Anhy-
drous solvents were purchased from Aldrich and degassed
before use. Grubbs’ catalyst (PCy3)2Ru(dC(H)Ph)Cl2 was pur-
chased from Strem Chemicals. NMR spectra were recorded
using a Varian 400 MHz spectrometer. Gas chromatographic
analyses were performed on a Hewlett-Packard HP 5890 II
equipped with a FID and a HP-5 column.
Gen er a l P r oced u r e for P r ep a r a tion of 3 a n d 4. In a
glovebox, a 200 mL Schlenk flask was charged with IMes‚HCl
(3.1 g, 9.10 mmol) or SIMes‚HCl (3.1 g, 9.10 mmol), potassium
tert-amylate (1.26 g, 10.0 mmol), and hexane (40 mL). The
reaction mixture, a slightly turbid, yellow solution, was stirred
at room temperature for 1 h. (PCy3)2Ru(dC(H)Ph)Cl2 (5.0 g,
6.1 mmol) was added to the reaction flask as a solid over 30
min. The flask was taken out of the glovebox, connected to a
Schlenk line, and placed under 1 atm of argon. The reaction
mixture was then stirred at room temperature for 12 h (in the
case of the IMes‚HCl reaction) or heated to 50 °C for 4.5 h,
allowed to cool to room temperature, and stirred 12 h (in the
case of the SIMes‚HCl reaction). During this time the original
purple color of the reaction mixture changed to brown-pink.
The brown-pink precipitate was then filtered under argon with
the help of a collection frit, and the collected solid was washed
with methanol (3 × 10 mL) and dried in vacuo to afford the
pure product (4.80 g, 92% (3) or 3.99 g, 77% (4)). (A similar
protocol in the preparation of 4 could be followed with SIMes‚
HBF4, employing SIMes‚HBF4 (100 mg, 0.3 mmol) and potas-
sium tert-amylate (65 mg, 0.3 mmol) in 5 mL of hexane,
stirring for 1.5 h, then adding (PCy3)2Ru(dC(H)Ph)Cl2 (150
mg, 0.2 mmol) and heating the purple mixture to 60 °C for 2
h followed by workup. An additional step was required during
workup, namely, extraction of the pink-brown product into
benzene, following initial washing with small portions of
hexane and methanol, evaporation of the benzene extracts, and
drying of the residue in vacuo. A yield of 102 mg, 67%, was
obtained.)
Ack n ow led gm en t. The National Science Founda-
tion, the Louisiana Board of Regents, the Petroleum
Research Fund administered by the ACS, NSERC (for
a PDF fellowship to L.J .), and Boehringer-Ingelheim
Pharmaceuticals Inc. are gratefully acknowledged for
financial support.
Su p p or tin g In for m a tion Ava ila ble: NMR spectra (1H
and 31P) for product of reactions using IMesHCl, SIMesHCl,
and SIMesHBF4 are provided. This material is available free
of charge via the Internet at http://pubs.acs.org.
OM0109511