Highly active water-soluble olefin metathesis catalyst

Article abstract of DOI:10.1021/ja058451c

A novel water-soluble ruthenium olefin metathesis catalyst supported by a poly(ethylene glycol) conjugated saturated 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligand is reported. The catalyst displays improved activity in ring-opening metathesis polymerization, ring-closing metathesis, and cross-metathesis reactions in aqueous media. Copyright

Full text of DOI:10.1021/ja058451c

Published on Web 02/25/2006
Highly Active Water-Soluble Olefin Metathesis Catalyst
Soon Hyeok Hong and Robert H. Grubbs*
Arnold and Mabel Beckman Laboratory of Chemical Synthesis, DiVision of Chemistry and Chemical Engineering,
California Institute of Technology, Pasadena, California 91125
Received December 13, 2005; E-mail: rhg@caltech.edu
Olefin metathesis is a powerful carbon-carbon bond formation
reaction in both polymer and small molecule synthesis.1 In
particular, the recent development of ruthenium olefin metathesis
catalysts, which show high activity and functional group tolerance,
has expanded the scope of olefin metathesis. However, performing
olefin metathesis in aqueous media is still challenging due to the
lack of a stable and active catalyst soluble in water. Aqueous olefin
metathesis has the economic, environmental, and processing benefits
of both homogeneous aqueous catalysis and aqueous two-phase
Scheme 1. Synthesis of Catalyst 4
complex 9 generated the desired catalyst 4 (Scheme 1). Catalyst 4
was purified by column chromatography followed by precipitation
from dichloromethane into diethyl ether. Attempts to synthesize a
phosphine-containing version of this catalyst were unsuccessful.
Complex 4 is stable in water. In the H NMR recorded in D
2
catalysis. Further, aqueous olefin metathesis is critical for some
biological applications of olefin metathesis.
1
2
O,
no signal corresponding to the benzylidene proton (RudCHPh, δ
6.4 ppm, CD Cl ) was observed. Initially, this was believed to be
either due to deuterium exchange of the benzylidene proton or
from rapid decomposition of 4 in D O. However, upon extracting
the catalyst with CD Cl from the D O solution, the benzylidene
peak reappeared. Even after 1 week in D
after CD Cl extraction, were not significantly altered, showing
1
2
2
3
d
2
2
2
2
1
2
O, the H NMR spectra,
2
2
8
stability of this catalyst in water. This type of solvent-dependent
NMR behavior has been reported in micelle-type complexes. We
believe that catalyst 4 aggregates could form a micelle-like structure
With the goal of developing a homogeneous catalyst that displays
increased activity and stability, our group has reported several water-
9
3
3
4
soluble catalysts, such as 1, 2, and 3. Catalysts 1-3 are unable
to mediate the ring-closing metathesis (RCM) reaction of simple
R,ω-dienes in water and show limited RCM activity in methanol.
Moreover, they do not show any activity in cross-metathesis (CM)
reactions in protic media. The recently developed catalyst 3
containing an N-heterocyclic carbene (NHC)-based ligand shows
improved activity in aqueous ring-opening metathesis polymeriza-
2
in D O due to the hydrophilic PEG chain and hydrophobic
10
ruthenium center.
As an activity comparison, we examined the ROMP of endo-
11
norbornene monomer 10 with catalysts 2, 3, and 4. As shown by
Figure 1, catalyst 4 showed much improved activity when compared
12
to other water-soluble catalysts. This is consistent with past results
as saturated NHC-based ruthenium olefin metathesis catalysts are
known to be more active than phosphine-based and unsaturated
4
tion (ROMP) reactions. Appending poly(ethylene glycol) (PEG)
to the nondissociating NHC ligand allows catalyst 3 to remain in
solution throughout the entire metathesis reaction. However, having
the PEG-carbamoyl-benzyl group as a pendant group of NHC
limited the stability of the complex 3. Earlier studies have shown
5,6
NHC-based catalysts.
RCM reactions of water-soluble R,ω-dienes have been highly
challenging due to instability toward water of the Ru methylidene
3b
species generated after the first catalytic turnover. There have
that 1,3-diaryl group of NHCs in (NHC)(L)(Cl)
2
RudCHPh-type
13
been a few reports of RCM of R,ω-dienes in water. However,
complexes are important for catalyst stability.5 As part of the
ongoing effort to use PEG as a water solubilizing moiety, we have
developed the novel water soluble catalyst 4 which shows improved
stability and activity in water. Appending PEG on the backbone of
2
saturated 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene (H IMes)
ligand renders catalyst 4 soluble in organic solvents, such as
dichloromethane and toluene, as well as water, with maintaining
stability and activity of well-known H
metathesis catalysts.6
2
IMes-based ruthenium
Catalyst 4 was prepared in three steps from readily available
starting materials. PEG-attached diamine 7 was synthesized using
an S 2-type reaction between N,N′-dimesityl-2,3-diamino-1-pro-
N
panol 57 and PEG mesyl methyl ether 6. The diamine 7 was
subsequently converted to the corresponding imidazolium salt 8
through condensation with triethyl orthoformate in the presence of
ammonium tetrafluoroborate. Deprotonation of 8 with potassium
bis(trimethylsilyl)amide (KHMDS) followed by the addition of Ru
Figure 1. A comparison of the ability of water-soluble catalysts to
polymerize endo-monomer 10 (data for catalyst 2 and 3 are obtained from
ref 4).
3508
9
J. AM. CHEM. SOC. 2006, 128, 3508-3509
10.1021/ja058451c CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Cross-Metathesis Reactions in Aqueous Mediaa
Table 1. Ring-Closing Metathesis Reactions in Aqueous Mediaa
a
Reactions were carried out at 45 °C with 5 mol % of catalyst 4 and an
initial substrate concentration of 0.2 M in D2O or H2O. Conversions were
1
b
c
determined by H NMR spectroscopy. E/Z ∼ 15:1. 6% of 24 remains
due to thermodynamic equilibrium.
Acknowledgment. We would like to thank Jason P. Jordan for
generous donation of substrate 12 and helpful discussions. The
National Institutes of Health (5R01GM068647) is acknowledged
for financial support.
Supporting Information Available: Experimental details and
characterization data. This material is available free of charge via the
Internet at http://pubs.acs.org.
a
Reactions were carried out at room temperature with 5 mol % of catalyst
4
and an initial substrate concentration of 0.2 M in D2O or H2O. Conversions
were determined by H NMR spectroscopy.
1
References
the reported reactions either involved water-insoluble substrates or
water-insoluble catalysts.13 The actual metathesis reactions in these
systems are believed to occur in organic-friendly environments, such
as inside solid supports, as a decrease in activity is observed with
water-soluble R,ω-dienes. The best reported conversion of RCM
of diallylamine hydrochloric acid salt 16 in water was just 11% at
5 °C.1 In homogeneous systems, there has been no report of the
RCM of the R,ω-dienes in aqueous media.
(1) (a) Handbook of Metathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weinheim,
Germany, 2003. (b) Ivin, K. J.; Mol, J. C. Olefin Metathesis and Metathesis
Polymerization; Academic Press: San Diego, CA, 1997.
(
2) Aqueous-Phase Organometallic Catalysis; Cornils, B., Hermann, W. A.,
Eds; Wiley-VCH: Weinheim, Germany, 2004.
(
3) (a) Mohr, B.; Lynn, D. M.; Grubbs, R. H. Organometallics 1996, 15,
4317-4325. (b) Kirkland, T. A.; Lynn, D. M.; Grubbs, R. H. J. Org.
Chem. 1998, 63, 9904-9909. (c) Lynn, D. M.; Mohr, B.; Grubbs, R. H.;
Henling L. M.; Day, M. W. J. Am. Chem. Soc. 2000, 122, 6601-6609.
(d) Lynn, D. M.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 3187-
3b
4
14
3193.
Catalyst 4 showed unprecedented RCM activity with water-
soluble R,ω-dienes in water yielding the corresponding five- and
six-membered rings in good to excellent yields (Table 1). RCM of
(
(
(
4) Gallivan, J. P.; Jordan, J. P.; Grubbs, R. H. Tetrahedron Lett. 2005, 46,
2577-2580.
5) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18-29 and
references therein.
6) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1,
1
2 and 14 produced the corresponding five-membered and six-
9
53-956. (b) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A.
membered ring compounds, 13 and 15, quantitatively (entries 1
and 2). In RCM of 16, cycloisomerized product 18 was observed
along with the major metathesis product 17 (entry 3). This type of
cycloisomerization has previously been observed during olefin
metathesis, presumably by ruthenium hydrides from catalyst
decomposition.1
H. J. Am. Chem. Soc. 2000, 122, 8168-8179. (c) Bielawski, C.; Grubbs,
R. H. Angew. Chem., Int. Ed. 2000, 39, 2903-2906.
(7) Mayr, M.; Buchmeiser, M. R.; Wurst, K. AdV. Synth. Catal. 2002, 344,
7
12-719.
8) After a week, 71% of the catalyst 4 was recovered by evaporation of
O.
(9) B u¨ t u¨ n, V.; Armes, S. P.; Billingham, N. C. Macromolecules 2001, 34,
(
D
2
3b,15
For the other substrates (entries 1, 2, 4, and
1148-1159.
5
), the corresponding cycloisomerized products were not observed.
(10) Well-ordered micelle formation of catalyst 4 aggregates in water is unlikely
due to short hydrophobic chain length. For conditions of micelle formation,
see: Dwars, T.; Paetzold, E.; Oehme, G. Angew. Chem., Int. Ed. 2005,
Allyl-2-methylallylamine hydrochloride 19 was cyclized to generate
a trisubstituted olefin 20 with relatively lower yield (entry 4). For
reasons not yet fully understood, RCM of diallyldimethylamine
chloride 21 was not successful (entry 5).
Cross-metathesis is also challenging in aqueous media. To the
best of our knowledge, there have been no reports of homogeneous
cross-metathesis in water. The Blechert group demonstrated homo-
44, 7174-7199.
(11) Earlier work demonstrated that endo-norbornene monomers are challenging
ROMP substrates when compared to exo-norbornene monomers. See refs
1
and 4.
(12) Catalyst 2 and 3 require 1 equiv of HCl, relative to catalyst, as a phosphine
scavenger to reach their highest conversions.
(
13) (a) Zarka, M. T.; Nuyken, O.; Weberskirch, R. Macromol. Rapid Commun.
2004, 25, 858-862. (b) Connon, S. J.; Blechert, S. Bioorg. Med. Chem.
Lett. 2002, 12, 1873-1876. (c) Davis, K. J.; Sinou, D. J. Mol. Catal. A:
Chem. 2002, 177, 173-178.
2
dimerization of allyl alcohol 23 in D O up to 80% conversion using
the aforementioned heterogeneous catalyst system.1 Catalyst 4
shows excellent activity in homodimerization of 23 and the self-
metathesis of cis-2-butene-1,4-diol 24 in water (Table 2). However,
cross-metathesis reaction with catalyst 4 is highly substrate de-
pendent. 4 is unable to homodimerize vinylacetic acid, allylamine
hydrochloride, and other water-soluble olefins derived from car-
boxylic acid and quaternary ammonium salts. Variations of pH using
DCl or NaOD solutions did not improve the cross-metathesis
activity of catalyst 4.
3b
(14) To avoid the methylidene intermediates, substituted dienes, such as
N-allylcinnamylamine hydrochloride salt, were required. Using these
substituted dienes is not an atom economical transformation since it has
unnecessary substituents which require additional steps for preparation.
Moreover, the yields of the RCM reactions with the substituted dienes
using catalysts 1-3 in water were usually not good. See ref 3b.
(
15) (a) Terada, Y.; Arisawa, M.; Nishida, A. Angew. Chem., Int. Ed. 2004,
43, 4063-4067. (b) Hong, S. H.; Day, M. W.; Grubbs, R. H. J. Am. Chem.
Soc. 2004, 126, 7414-7415. (c) Hong, S. H.; Sanders, D. P.; Lee, C. W.;
Grubbs, R. H. J. Am. Chem. Soc. 2005, 127, 17160-17161. (d) C¸ etinkaya,
B.; Demir, S.; O¨ zdemir, I.; Toupet, L.; S e´ meril, D.; Bruneau, C.; Dixneuf,
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Onishi, T.; Ogoshi, S.; Kurosawa, H. J. Organomet. Chem. 2000, 616,
A novel water-soluble catalyst which is active and stable in water
has been developed. This catalyst shows unprecedented activity in
ROMP, RCM, and CM in aqueous media.
135-139.
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J. AM. CHEM. SOC.
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