A robust and recyclable ruthenium catalyst immobilised on polyethylene glycol

Article abstract of DOI:10.1016/j.tetlet.2009.07.022

A highly robust and recyclable Hoveyda-Grubbs' second generation ruthenium type catalyst immobilised on polyethylene glycol is conveniently prepared from Grubbs' second generation catalyst. The catalyst performs ring-closing metathesis of various di-and tri-substituted olefins efficiently in dichloromethane in air.

Full text of DOI:10.1016/j.tetlet.2009.07.022

Tetrahedron Letters 50 (2009) 5340–5343
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A robust and recyclable ruthenium catalyst immobilised on polyethylene glycol
b,
Shazia Zaman a, , Andrew D. Abell
*
*
a Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch, New Zealand
b School of Chemistry & Physics, The University of Adelaide, North Terrace, Adelaide SA 5005, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly robust and recyclable Hoveyda-Grubbs’ second generation ruthenium type catalyst immobilised
on polyethylene glycol is conveniently prepared from Grubbs’ second generation catalyst. The catalyst
performs ring-closing metathesis of various di-and tri-substituted olefins efficiently in dichloromethane
in air.
Received 19 May 2009
Revised 19 June 2009
Accepted 3 July 2009
Available online 9 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
A number of well-defined and functional group-tolerant metath-
esiscatalystsarenowknown,forexample,therutheniumalkylidenes
1a–c and the more recent 2a,b1,2 (Fig. 1) Theunique bidentate nature
of the isopropoxy ether ligand of 2 results in enhanced stability in air
and an ability to recycle the catalyst by chromatography on silica
gel.2c Immobilisedandsupportedrutheniumcatalystshavealsobeen
reported that allow ease of removal of ruthenium by-products and
catalyst recycling.3 A number of catalysts of this type are known,
but few display good reactivity and recyclability.4
Early reports on such supported catalysts employed heteroge-
neous polystyrene (PS) as the support.5 However, while these cat-
alysts can be recycled, they generally display poor catalytic activity
due to limited access to the reactive site of the catalyst.5 Catalysts
based on soluble supports show improved activity with enhanced
rates of diffusion relative to the heterogeneous polymers.6–9 These
catalysts can be recovered by precipitation or aqueous extraction
following metathesis.6,7 For example, the soluble-PEG-supported
catalysts 3 and 4 exhibit good ring-closing metathesis (RCM) activ-
ity in dichloromethane under homogenous conditions and can be
recycled to some degree.8,9 Significantly, the NHC-immobilised cat-
alysts 5 and 6 show some activity under aqueous conditions.6a,b
Here we report the synthesis of 7 (an air-stable Hoveyda-Grub-
bs’ second generation type catalyst) and its use in RCM reactions of
various di- and tri-substituted dienes to give five-, six- and seven-
membered cyclic olefins (see Table 2).
conditions11 to give styrene 11. Polyethylene glycol monomethyl
ether (Mn = 2000) was deprotonated with sodium hydride and 11
was added to this anion to give the PEG-tethered ligand 12
L
Ru
L
Ru
O
L
Ph
Cl
Cl
Cl
Cl
Cy3
a
b
PCy3
N
N
N
Mes
Mes
Mes
Mes
1
1c
N
2
MesN NMes
NMes
MesN
Cl
Cl
Cl
Cl
Ru
O
Ru
O
O PEG
2
O
PEG
O
O
3
4
O
MePEG O
N
H
NMes
N
Cl
Cl
Ru
Ph
PCy3
5
OPEGMe
Ruthenium catalyst 7 is suitable for reaction in reagent grade
dichloromethane10 without drying or degassing and can be recy-
cled by precipitation or aqueous extraction.
The synthesis of 7 is shown in Scheme 1. Chloromethylation of 9
(itself prepared from commercially available 8) gave the chloro-
methyl benzaldehyde 10, which was reacted under standard Wittig
NMes
MesN
Cl
Cl
MesN NMes
Ru
Cl
Cl
Ru
O
O
OPEGMe
7
6
PEGMe :
O
O
n Me
* Corresponding authors. Tel.: +61 8 8303 5652; fax: +61 8 8303 4358.
E-mail addresses: shazia.zaman@canterbury.ac.nz (S. Zaman), andrew.abell@
adelaide.edu.au (A.D. Abell).
Figure 1. Ruthenium catalysts for olefin metathesis.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.022

S. Zaman, A. D. Abell / Tetrahedron Letters 50 (2009) 5340–5343
5341
Table 1
(Scheme 1). An attempted preparation of 12, by reaction of 10 di-
rectly with polyethylene glycol monomethyl ether, followed by
Wittig olefination was problematic due to difficulties in removal
of triphenylphosphine at this late stage. Treatment of 12 with
Grubbs’ second generation catalyst (1b), in the presence of CuCl
to scavenge tricyclohexylphosphine, gave the PEG-immobilised
catalyst 7 as a green solid in 67% yield after purification by chroma-
tography on alumina and precipitation with ether. The structure of
7 was confirmed by 1H and 13C NMR, and MALDI-TOF mass spec-
trometry. In particular, the MALDI-TOF mass spectrum revealed
an intense peak for the [MH+]Na ion at 2662 Da, which is consis-
tent with the 45 ethylene oxides (CH2CH2O) associated with PEG.
The 1H NMR spectrum (CDCl3) showed a characteristic resonance
for the benzylidene proton at 16.5 ppm.12
Recyclability studies of catalyst 7 in RCM of diene 13
Ts
N
Ts
N
7
10 mol%
CH2Cl2,
reflux
14
13
Cycle
Conversiona (%)
1
2
3
4
5
>98
95
95
90
89
a
Determined by analysis of the crude 1H NMR spectrum.
Table 2
Ring-closing metathesis of various di- and tri-substituted dienes
Entry
1
Substratereference
Product
Catalyst
Time (h)
Conversiona (%)
7
1b
0.5
0.5
>98
>98
Tsb
N
Ts
N
1416
1316
2
3
7
1b
0.5
0.5
>98
>98
EtO2C CO2Et
EtO2C CO2Et
1618
1518
7
1b
0.5
0.5
>98
>98
Ts
N
Ts
N
1716
1816
4
7
1b
0.5
0.5
95
98
Ts
N
Ts
N
1916
2019
5
6
7
a
7
1b
0.5
0.5
98
98 (1:1)
Ts
N
Ts
N
Ts
N
2116
2218
2320
7
1b
0.5
0.5
98
98
Ts
N
Ts
N
2421
2521
7
1b
2
4
94
85
O
O
Ph
O
O
Ph
Ph
N
O
Ph
N
O
2622
2722
Determined by analysis of the crude 1H NMR spectrum.
4-Toluenesulfonyl.
b

5342
S. Zaman, A. D. Abell / Tetrahedron Letters 50 (2009) 5340–5343
In summary, we have reported a new polyethylene glycol-sup-
O
O
H
H
O
H
ported ruthenium catalyst 7 that performs RCM reactions in air
using reagent grade dichloromethane. The catalyst is conveniently
prepared by reaction of Grubbs’ second generation catalyst with
PEG-bound olefin 12. It is stable in air for several months and per-
forms well in RCM of a variety of dienes. The catalyst can be recy-
cled up to five times and is easily recovered on precipitation with
ether or by aqueous extraction. Catalyst 7 represents a useful addi-
tion to the growing list of supported metathesis catalysts and work
is under progress to extend its activity to aqueous conditions.
HO
O
O
iPrBr
HCHO
K2CO3
DMF, 70%
HCl gas,
35%
9
8
Ph3P+CH3Br-
O
Cl
Cl
THF, KOtBu
81%
10
11
Acknowledgements
O
HOPEGMe
The authors would like to thank the Waikato University MALDI-
TOF Mass spectrometry services. Financial support from the Royal
Society of New Zealand Marsden fund and the Australian Research
Council (ARC) is gratefully acknowledged. The authors also thank
Professor Robert Grubbs at the Division of Chemistry and Chemical
Engineering, California Institute of Technology, Pasadena, USA, and
Dr. Axel Neffe at the Institute of Polymer Research Centre GKSS
Forschungszentrum GmbH, Teltow, Germany for initial
discussions.
OPEGMe
NaH, DMF
81%
12
NMes
H
MesN
CuCl, CH2Cl2
1b
Cl
Cl
Ru
O
, 50 ºC, 67%
OPEGMe
H = 16.5 ppm
7
References and notes
Scheme 1. Synthesis of catalyst 7 from 2-hydroxybenzaldehyde 8.
1. (a) Grubbs, R. H.; Trnka, T. M.; Sanford, M. S. Curr. Meth. Inorg. Chem. 2003, 3,
187–231; (b) Bielawski, C. W.; Benitez, D.; Grubbs, R. H. Science 2002, 297,
2041–2044; (c) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413–4450.
2. (a) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; 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; (c) Hoveyda, A. H.; Gillingham, D.
G.; Van Veldhuizen, J. J.; Kataoka, O.; Garber, S. B.; Kingsbury, J. S.; Harrity, J. P.
A. Org. Biomol. Chem. 2004, 2, 8–23.
The ability of 7 to catalyse RCM of N-tosyldiallylamine 13 (a
metathesis benchmark substrate)13 was then investigated, and
the results are summarised in Table 1 for five repeated cycles. N-
Tosyldiallylamine 13 was heated under reflux with 10 mol % of cat-
alyst 7 for 1 h in non-degassed dichloromethane, with exposure to
air. Ether was added to precipitate the catalyst and the filtrate was
concentrated and analysed by 1H NMR spectroscopy which showed
complete conversion to 14.14 The filtered catalyst was reused in a
further RCM reaction of 13 to give a 95% conversion to 14. This se-
quence was repeated three more times without significant loss of
activity (Table 1).
A comparative study of our new catalyst 7 and Grubbs’ second
generation catalyst 1b was carried out with an extended set of di-
and tri-substituted dienes (13, 15, 17, 19, 21, 24 and 26), and the
results are given in Table 2. In all cases, the reaction involved heat-
ing the substrate under reflux with 10 mol % of catalyst, with the
extent of conversion to the five-, six- and seven-membered cyclic
olefins 14, 16, 18, 20, 22, 23, 25 and 27 being determined by 1H
NMR analysis of the crude product (see Table 2). Catalyst 7 was re-
moved prior to analysis by simple aqueous extraction.14 Reactions
with catalyst 1b were carried out using dry degassed dichloro-
methane under inert conditions, while those with 7 were carried
out with exposure to air.15
3. Buchmeiser, M. R. Chem. Rev. 2009, 109, 303–321.
4. Zaman, S.; Curnow, O. J.; Abell, A. D. Aust. J. Chem. 2009, 62, 91–100.
5. (a) Nguyen, S. T.; Grubbs, R. H. J. Organomet. Chem. 1995, 497, 195; (b) Schurer,
S. C.; Gessler, N.; Buschmann, N.; Blechert, S. Angew. Chem., Int. Ed. 2000, 39,
3898–3901.
6. (a) Hong, S. H.; Grubbs, R. H. J. Am. Chem. Soc. 2006, 128, 3508–3509; (b)
Gallivan, J. P.; Jordan, J. P.; Grubbs, R. H. Tetrahedron Lett. 2005, 46, 2577–2580;
(c) Connon, S. J.; Blechert, S. Bioorg. Med. Chem. Lett. 2002, 12, 1873–1876; (d)
Zarka, T.; Nuyken, O.; Weberskirch, R. Macromol. Rapid Commun. 2004, 25, 858–
862.
7. Hong, S. H.; Grubbs, R. H. Org. Lett. 2007, 9, 1955–1957.
8. (a) Yao, Q.; Motta, A. R. Tetrahedron Lett. 2004, 45, 2447–2451; (b) Yao, Q.
Angew. Chem., Int. Ed. 2000, 39, 3896–3898.
9. Varray, S.; Lazaro, R.; Martinez, J.; Lamaty, F. Organometallics 2003, 22, 2426–
2435.
10. Suitable for general laboratory preparation.
11. Jordan, J. P.; Grubbs, R. H. Angew. Chem., Int. Ed. 2007, 46, 5152–5155.
12. Synthesis of 7: To a suspension of NaH (60 mg, 1.53 mmol) in dry DMF (80 ml)
was added PEGOMe (Mn = 2000, 2.4 g, 1.22 mmol) and the mixture was stirred
at rt for 30 min. A solution of 118 (320 mg, 1.53 mmol) in dry DMF (5 ml) was
added and the reaction mixture was stirred for 18 h. DMF was evaporated in
vacuo, the residue was redissolved in CH2Cl2 and the mixture was filtered
through a plug of Celite. The filtrate was concentrated in vacuo, dissolved in
CH2Cl2 (3 ml) and excess ether was added to give 12 as a white precipitate
(2.15 g, 81%). 1H NMR (CDCl3, 500 MHz), d 1.10 (d, J = 5 Hz, 6H), 3.13 (s, 3H),
3.26–3.84 (br m, PEG), 4.24–4.29 (m, 3H), 4.98 (d, J = 10.5 Hz), 5.49 (br d,
J = 17.5 Hz, 1H), 6.61 (d, J =8.0 Hz, 1H), 6.77 (dd, J = 17 Hz, 11 Hz, 1H), 6.93 (d,
J = 8 Hz, 1H), 7.20 (s, 1H) 13C NMR (CDCl3, 126 MHz), d 21.67, 58.46, 61.02,
68.61, 69.78, 69.95, 70.00, 70.02, 70.03 (br), 70.31, 71.37, 72.02, 72.39, 113.52,
113.58, 125.78, 127.07, 127.96, 129.66, 131.26, 154.14. To a suspension of CuCl
(55 mg, 0.39 mmol) in dry CH2Cl2 under dry N2 was added 12 (433 mg,
0.19 mmol) followed by 1b (169 mg, 0.19 mmol). The mixture was heated at
50 °C for 1.5 h, then cooled to rt and passed through a plug of Celite. The
solvent was removed in vacuo and the solid was passed through a column of
neutral alumina (Brockmann grade III) eluting with MeOH/CH2Cl2 (97:3). The
green band was collected, evaporated in vacuo and redissolved in minimal
CH2Cl2. Excess ether was added to precipitate 7 as a green powder (355 mg,
67%). 1H NMR (CDCl3, 500 MHz), d 1.20 (d, J = 6 Hz, 6H), 1.27–2.43 (m, 18H),
2.64 (t, J = 5.7 Hz, 2H), 3.32 (s, 3H), 3.35–3.82 (br m, PEG), 4.12 (s, 4H), 4.47 (s,
2H), 4.82–4.87 (m, 1H), 6.70 (d, J = 9 Hz, 1H), 6.80 (s, 1H), 7.01 (s, 4H), 7.43 (d,
J = 8.7 Hz, 1H), 16.5 (s, 1H); 13C NMR (CDCl3, 75 MHz), d 20.90, 20.97, 58.88,
61.54, 68.90, 70.20, 70.41, 70.46, 71.78–72.36 (br, PEG), 74.97, 112.62, 121.91,
128.36, 128.84, 129.23, 131.95, 138.63, 145.02, 151.69, 211.12, 296.17. TOF
MS = [MH]+ Na: 2662.763 (containing 45 CH2CH2O units).
Reactions of 1316 under these conditions with either catalyst led
to quantitative conversion to 14.17 The dienes, 15,18 17,16 1916 and
2421 similarly led to quantitative (or near quantitative) conver-
sions to the corresponding five- six- and seven-membered alkenes
(Table 2, entries 2–4 and 6). In the case of diene 21,18 significant
isomerisation of the product alkene was observed with catalyst
1b to give 2218 and 2320 in a ratio of 1:1 (Table 2, entry 5). In this
case the crude product was purified by chromatography on silica
gel (using 5% ethyl acetate in hexane) to give 67% of 2320 and
33% of 22.18 Some isomerisation was apparent on silica.
Treatment of 2622 with 1b led to 85% conversion to 2722 after an
extended reaction for 4 h under degassed conditions, while the
reaction in the presence of 7 led to 94% conversion after only 2 h
(Table 2, entry 7). The product 27 was isolated in yields of 89%
(from reaction with 7) and 80% (from reaction with 1b), respec-
tively, after chromatography.

S. Zaman, A. D. Abell / Tetrahedron Letters 50 (2009) 5340–5343
5343
13. (a) Kirschning, A.; Jas, G.; Kunz, U. Chem. Eur. J. 2003, 9, 5708–5723; (b)
Michrowska, A.; Gulajski, L.; Kaczmarska, Z.; Mennecke, K.; Kirschning, A.;
Grela, K. Green Chem. 2006, 8, 685–688; (c) Gulajski, L.; Michrowska, A.;
Naroznik, J.; Kaczmarska, Z.; Rupniki, L.; Grela, K. ChemSusChem 2008, 1, 103–
109.
14. Typical procedure for RCM using 7: To a solution of the substrate (50 mg) in
reagent grade CH2Cl2 (5 ml) was added 7 (10 mol%) and the solution was
heated under reflux for the time specified in Table 1 or 2. The solution was
concentrated in vacuo, redissolved in minimal CH2Cl2 and excess ether was
added. The catalyst was isolated by filtration. The filtrate was evaporated in
vacuo and the residue was analysed by 1H NMR. The catalyst was removed by
aqueous extraction for the reactions shown in Table 2.
15. Typical procedure for RCM using 1b: To a solution of the substrate (50 mg) in
dry, degassed CH2Cl2 (5 ml) was added 1b (10 mol%) and the solution was
heated under reflux under an atmosphere of N2 for the time specified in Table
2. The solution was concentrated in vacuo and the residue was analysed by 1H
NMR.
18. Yao, Q. J. Am. Chem. Soc. 2004, 126, 74–75.
19. Tamaru, Y.; Hojo, M.; Yoshida, Z.-i. J. Org. Chem. 1988, 53, 5731–
5741.
20. Clavier, H.; Nolan, S. P. Chem. Eur. J. 2007, 13, 8029–8036.
21. Cheng, H.-Y.; Sun, C.-S.; Hou, D.-R. J. Org. Chem. 2007, 72, 2674–
2677.
22. Benzyl allyl (2-benzylbut-3-enoyl) carbamate 26: 1H NMR (CDCl3, 500 MHz) d
2.79 (dd, J = 13.5 Hz, 7.5 Hz, 1H), 3.17 (dd, J = 13.5 Hz, 7.2 Hz, 1H), 4.23–4.26
(m, 2H), 4.68 (q, J = 7.5 Hz, 1H), 4.99–5.07 (m, 4 H), 5.18 (s, 2H), 5.64–5.71 (m,
1H), 5.88–5.95 (m, 1H), 7.14–7.17 (m, 4H), 7.21–7.24 (m, 2H) 7.26–7.39 (m,
2H), 7.32–7.45 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 39.00, 46.54, 51.42, 68.52,
116.76, 117.36, 126.13, 128.12, 128.19, 128.57, 128.59, 129.24, 132.74, 134.92,
136.30, 138.99, 153.97, 175.80. [MH]+ C22H24NO3 requires: 350.1711 observed:
350.1693; benzyl 5-benzyl-6-oxo-5,6-dihydropyridine-1(2H)-carboxylate 27:
1H NMR (CDCl3, 500 MHz)
d 3.00 (dd, J = 13.5 Hz, 7.5 Hz, 1H), 3.17 (dd,
J = 13.5 Hz, 4.5 Hz, 1H), 3.35–3.38 (m, 1H), 3.79 (d, J = 14.0 Hz, 1H), 4.14 (d,
J = 14.5 Hz, 1H), 5.29 (s, 2H), 5.63–5.66 (m, 1H), 5.72–5.75 (m, 1H), 7.14–7.19
(m, 4H), 7.20–7.39 (m, 2H) 7.32–7.45 (m, 4H); 13C NMR (CDCl3, 75 MHz) d
38.88, 45.89, 47.13, 68.51, 121.52, 125.21, 126.58, 128.03. 128.19, 128.30,
128.51, 129.27, 135.20, 137.29, 153.37, 171.00; HRMS (EI) observed: 322.1448.
[MH]+ C20H20NO3 requires: 322.1443.
16. Terada, Y.; Mitsuhiro, M.; Nishida, A. Angew. Chem. 2004, 116, 4155–4157.
Angew. Chem., Int. Ed. 2004, 43, 4063–4067.
17. A closer examination of the reaction of 13 with 7 revealed that the reaction was
complete in 30 min, and as such, this reaction time was used throughout, with
the exception of 26 which required longer reaction times.