Highly active silica gel-supported metathesis (pre)catalysts

Article abstract of DOI:10.1002/adsc.200505106

Highly active Hoveyda-Grubbs and Hoveyda-Blechert type (pre)catalysts, immobilized on silica gel, are presented. These (pre)catalysts are synthesized in a few steps from readily available precursors and demonstrate high activity in a number of test metath

Full text of DOI:10.1002/adsc.200505106

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Highly Active Silica Gel-Supported Metathesis (Pre)Catalysts
Dirk Fischer, Siegfried Blechert*
Institute of Organic Chemistry, Technical University of Berlin, Straße des 17. Juni 135, 10623 Berlin, Germany
Fax: (þ49)-30-314-23619, e-mail: blechert@chem.tu-berlin.de
Received: March 11, 2005; Accepted: May 6, 2005
Abstract: Highly active Hoveyda–Grubbs and Hov-
eyda–Blechert type (pre)catalysts, immobilized on
silica gel, are presented. These (pre)catalysts are syn-
thesized in a few steps from readily available precur-
sors and demonstrate high activity in a number of
test metathesis reactions. The catalyst is easily sepa-
rated by simple filtration of the non-swelling materi-
al.
Keywords: alkenes; immobilization; metathesis;
ruthenium; silica gel; supported catalysts
Since the development of commercially available
Grubbs[1] and Grubbs–Herrmann[2] catalysts, olefin
metathesis has emerged as a standard reaction in organ-
ic chemistry.[3] Further developments within this group
and by others have led to more stable derivatives of
these complexes containing a chelating isopropoxyben-
zylidene ligand.[4] These Hoveyda–Blechert type com-
plexes have the advantage of increased stability over
their phosphine-containing counterparts, whilst retain-
ing functional group tolerance and are even purifiable
by silica gel chromatography. Immobilized variants of
these complexes have been developed and combine
the functional group tolerance of homogeneous systems,
with the possibility of recyclability and the advantage of
simple work-up.[5] However, these supported systems
are generally immobilized on organic polymers which
typically suffer from a number of disadvantages includ-
ing diffusion-related disadvantages[6] or the require-
ment for the addition of solvent for precipitation of
the soluble carrier.[7]
Therefore, supported metathesis (pre)catalysts which
are easily separated by simple filtration are highly desir-
Scheme 1. a) i) Ac2O, AcOH, reflux, 12 h; ii) i-PrBr (7
able.
equivs.), K2CO3 (2 equivs.), N2, DMF, 508C, 12 h; iii) NaOMe,
Previous work from our group[8] and others[9] has
MeOH, yield 43% (over 3 steps); b) (3-iodopropyl)-trime-
shown that different substitution on the chelating o-iso-
thoxysilane (0.7 equivs.), NaH, DMF, N2, 08C, 1h, 30%; c)
propoxystyrene can greatly influence catalyst activity. In
particular, introduction of steric bulk at the ortho posi-
Ph3PCH3Br (2 equivs.), KO-t-Bu (1.9 equivs.), Et2O, 0 8C,
10 min, 70%; d) i) silica gel, toluene, N2, 808C, 12 h, 62%;
tion has led to some of the fastest initiating (pre)cata- ii) dimethoxydimethylsilane, 808C, 12 h.
lysts developed to date (1a/1b).[10] It was envisaged
that this increase of activity could be coupled with im-
Adv. Synth. Catal. 2005, 347, 1329–1332
DOI: 10.1002/adsc.200505106
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Dirk Fischer, Siegfried Blechert
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Table 1. Metathesis reactions with 7a/7b.
Scheme 2. a) Grubbs–Herrmann catalyst (0.1equiv.), CuCl
(0.1equiv.), CH Cl2, N2, 458C, 3 h, loading 33.6 mmol/g; b)
2
Grubbs catalyst (0.1equiv.), CH Cl2, N2, 458C, 3 h, loading
2
17.4 mmol/g
mobilization on silica gel to afford a highly active, filter-
able (pre)catalyst.
Styrene 5 required for immobilization, was readily
synthesized starting from catechol 2. Selective mono-
acylation, isopropylation and deprotection of the acetate
furnished the desired o-isopropyl ether 3 in good overall
yields. Alkylation with (3-iodopropyl)trimethoxysilane
afforded aldehyde 4 which was purified by kugelrohr
distillation. Subsequent Wittig olefination and purifica-
tion through a short pad of silica gel afforded 5 in high
purity in an overall yield of 9%.
The styrene 5 was immobilized on LiChroprep Si 60ꢁ
40–63 mm and 25–40mm[11] by heating a mixture of 1g of
silica gel per 1mmol of 5 in toluene to give a loading of
0.63 mmol/g. The ligand concentration on the surface of
the silica gel was determined by quantitative measure-
ment of remaining 5 by 1H NMR against stilbene as in-
ternal standard. The free Si-OH groups were subse-
quently capped with dimethoxydimethylsilane before
immobilization of the (pre)catalyst.
[a]
[b]
[c]
Conditions: 0.05 M, CH2Cl2, N2, 258C.
Determined by HPLC.
1
Determined by H NMR.
In the condensation of trialkoxysilanes on silica gel
the connection can be achieved by one, two or even
three bonds. It is know that two bonds dominate so we
assume 6 to be the structure of the functionalized silica uct showed good stability on storing at þ48C under ni-
gel.[12]
trogen over two weeks without any sign of decomposi-
By refluxing the Grubbs–Herrmann catalyst[2] with 1 tion. When quantitative loading of the styrene with
equivalent CuCl in dichloromethane with the function- ruthenium was achieved the (pre)catalyst decomposed
alized silica gel in a ratio of 10:1 to the immobilized li- within days at À208C. Synthesis of 7b was achieved in
gand, the immobilized (pre)catalyst was isolated, fol- a similar manner by reacting the Grubbs catalyst[1] to af-
lowing filtration and drying as a stable green-colored ford a brown-colored silica gel with 0.017 mmol/g active
silica gel 7a, with a loading of 0,034 mmol/g.[13] The prod- (pre)catalyst.
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Adv. Synth. Catal. 2005, 347, 1329–1332

Highly Active Silica Gel-Supported Metathesis (Pre)Catalysts
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Table 2. Recycling with 0.15% immobilized catalyst 7a.
lized catalysts 7a and 7b reached high conversion with
just 1% or, respectively, 0.5% ruthenium and showed
higher activity than the parent Grubbs catalyst.
Experimental Section
Run
Time
Conversion[a]
Ru-residue[b, c]
2-Isopropoxy-3-propyl-(3-trimethoxysilyl)-
benzaldehyde (4)
1
2
3
4
1 h
1h
1h
>99%
93%
68%
32 ppm
12 ppm
6 ppm
Under N2 compound 3[3i] (3 g, 16.6 mmol) was placed in dry
DMFand treated with NaH (380 mg, 15.8 mmol). After 30 mi-
nutes (3-iodopropyl)trimethoxysilane (2.15 mL, 11.0 mmol)
was added at 08C. After 30 minutes at room temperature the
reaction mixture was treated with saturated aqueous K2CO3
and extracted with Et2O. The organic layer was washed with sa-
turated aqueous K2CO3/NaCl, dried over MgSO4 and purified
by kugelrohr distillation; yield: 1.1 g (30%); 1H NMR
12 h
76%
12 ppm
[a]
Determined by HPLC.
Without purification.
[b]
[c]
Determined by TXRF[15] (Æ15%).
(Pre)catalyst 7a was tested in a variety of metathesis (500.1MHz, CDCl 3): d¼10.45 (s, 1H), 7.46 (dd, J1 ¼7.6 Hz,
J2 ¼1.7 Hz, 1H), 7.13–7.04 (m, 2H), 4.66 (sep, J¼6.2 Hz,
reactions and the results are summarized in Table 1.
The particle size of the carrier had no effect on the activ-
ity and work-up was accomplished by simple filtration
with an average ruthenium residue corresponding to
65 ppm (Æ15%).
1H), 3.99 (t, J¼6.5 Hz, 2H), 3.59 (s, 9H), 1.96 (tt, J1 ¼8.2 Hz,
J2 ¼6.5 Hz, 2H), 1.33 (d, J¼6.2 Hz, 6H), 0.84–0.78 (m, 2H);
13C NMR (126.3 MHz, CDCl3): d¼191.1 (d), 152.7 (s), 150.8
(s), 131.0 (s), 123.7 (d), 118.92 (d), 118.90 (d), 76.2 (d), 70.8
(t), 50.7 (q, 3C), 22.8 (t), 22.4 (q, 2C), 5.5 (t); IR (film): n¼
2974, 2943, 2842, 1748, 1687, 1582, 1085 cmÀ1; MS (70 eV):
m/z (%)¼342 (5) [Mþ], 121 (100), 163 (29), 226 (36).
Cyclization of 8 catalyzed by 7a at room temperature
was completed within one hour, but as can be seen by the
cyclization of 10 and 12, just 0.5% of catalyst 7b was
much more effective for the other two RCM reactions
attempted, albeit with a significantly lower turnover fre-
quency. Afterwards 7a was tested in ROM-RCM, RCM-
ROM-RCM and ROM-CM sequences, where conver-
sion in general was excellent. An exception is the trans-
formation of 16 to 17, which reached an equilibrium at
40%, an effect also seen with homogeneous catalysts.[14]
After we had proven the metathesis capability of 7a,
we were interested in its reusability. Most often immobi-
lized metathesis (pre)catalyst are used with 5 mol % of
the ruthenium complex. In our opinion this loading is
much too high and does not give reliable information
on reusability. Therefore a loading of 0.15% was chosen
and the results are given in Table 2.
2-Isopropoxy-1-propyl-(3-trimethoxysilyl)-3-
vinylbenzene (5)
Under N2 Ph3PCH3Br (1.4 g, 3.84 mmol) was placed in Et2O at
À108C and KO-t-Bu (393 mg, 3.50 mmol) was slowly added.
After 30 minutes 4 (600 mg, 1.75 mmol) was slowly added
and stirred for 15 minutes. The organic layer was washed
with saturated aqueous K2CO3/NaCl, dried over MgSO4 and
filtered over a pad of silica gel; yield: 418 mg (70%); 1H NMR
(500.1MHz, CDCl 3): d¼7.15–7.06 (m, 2H), 6.97 (t, J¼
7.9 Hz, 1H), 6.82–6.78 (m, 1H), 5.69 (dd, J1 ¼17.8 Hz, J2 ¼
1.1 Hz, 1H), 5.24 (dd, J1 ¼11.1 Hz, J1 ¼1.1 Hz, 1H), 4.45
(sept, J¼6.2 Hz, 1H), 3.94 (t, J¼6.5 Hz, 2H), 3.58 (s, 9H),
1.94 (tt, J1 ¼8.2 Hz, J2 ¼6.5 Hz, 2H), 1.28 (d, J¼6.2 Hz, 6H),
0.82 (m, 2H); 13C-NMR (126.3 MHz, CDCl3): d¼152.6 (s),
144.8 (s), 132.8 (s), 132.3 (d), 123.4 (d), 117.5 (d), 114.5 (t),
112.6 (d), 75.4 (d), 70.5 (t), 50.4 (q), 22.9 (t), 22.6 (q), 5.5 (q);
IR (film): n¼2973, 2942, 2840, 1574, 1459, 1086 cmÀ1; MS
(70 eV): m/z (%)¼340 (14) [Mþ], 121 (100), 224 (47), 266 (19).
Full conversion of 8 was achieved again within 1hour
and after filtration the next RCM run was filtered again
after 1hour and showed 93% conversion. The conver-
sion dropped off significantly for the third run after 1
hour, but by increasing the reaction time in the forth
run it was possible to achieve a respectable conversion.
Ruthenium contamination of the products were meas-
ured by TXRF, and in all cases were significantly lower
than previous reports of metathesis following silica gel
chromatography.[15]
The presented heterogeneous ruthenium complex is a
highly active metathesis catalyst. Standard silica gel was
functionalized within a few steps, immobilization of the
ruthenium complex has been achieved and the catalyst is
easily separated from the reaction mixture by simple fil-
Functionalized Silica Gel (6)
Under N2 toluene-washed silica gel (380 mg) was suspended in
toluene (20 mL). (E)-Stilbene (68.7 mg, 0.38 mmol) was added
as NMR standard. Compound 5 (130 mg, 0.38 mmol) was add-
ed and the suspension was stirred at 808C. After 12 hours dime-
thoxydimethylsilane (0.5 mL, 3.54 mmol) was added and stir-
red for an additional 12 hours. The silica gel was filtered, wash-
ed with CH2Cl2, Et2O, and then with pentane, before being
dried in vacuum; yield: 457 mg; loading (0.622 mmol/g); IR
tration. In different test reactions the silica gel immobi- (KBr): n¼2980, 2880, 1773, 1743, 1099, 805 cmÀ1
.
Adv. Synth. Catal. 2005, 347, 1329–1332
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Dirk Fischer, Siegfried Blechert
COMMUNICATIONS
e) J. O. Krause, S. H. Lubbad, O. Nuyken, M. R. Buch-
meiser, Macromol. Rapid Commun. 2003, 24, 875–878;
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Synlett 2001, 10, 1547–1550; g) J. S. Kingsbury, S. B.
Garber, J. M. Giftos, B. L. Gray, M. Okamoto, R. A. Far-
rer, J. T. Fourkas, A. H. Hoveyda, Angew. Chem. Int. Ed.
2001, 40, 4251–4255; h) K. Grela, M. Tryznowski, M. Bi-
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Weberskirch, Macromol. Rapid Commun. 2004, 25,
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Adv. Synth. Catal. 2002, 344, 712–719.
Hoveyda–Blechert Catalyst Loaded Silica Gel (7a)
Silica gel 6 (200 mg) was suspended in CH2Cl2 (20 mL) treated
with Grubbs–Herrmann catalyst (10.56 mg, 12.4 mmol) and
CuCl (1.231 mg, 12.4 mmol) and stirred for 3.5 h at 408C. The
green silica gel was filtered and washed again with CH2Cl2,
Et2O, pentane and dried in vacuum. Silica gel 7a (10 mg) was
treated with ethyl vinyl ether (0.5 mL)/PPh3 (0.8 mg) in reflux-
ing CH2Cl2 (3 mL) for 1h. The ruthenium amount in the fil-
trate was determined by TXRF. IR (KBr): n¼2980, 2879,
1755, 1472, 1099, 805 cmÀ1; Ru: (0.0336 mmol/g).
Hoveyda–Grubbs Catalyst Loaded Silica Gel (7b)
[6] S. T. Nguyen, R. H. Grubbs, J. Organomet. Chem. 1995,
497, 195.
Silica gel 6 (100 mg) was suspended in CH2Cl2 (10 mL) and
treated with Grubbs catalyst (5.25 mg, 6.38 mmol) for 2 h at
408C. The brown silica gel was filtered, washed with CH2Cl2,
Et2O and pentane and dried in vacuum. Silica gel 7b (10 mg)
was treated with ethyl vinyl ether (0.5 mL)/PPh3 (0.8 mg) in re-
fluxing CH2Cl2 (3 mL) for 1h. The ruthenium amount in the fil-
trate was determined by TXRF. IR (KBr): n¼2981, 2945, 2879,
2859, 1630, 1577, 1470, 1461, 1097, 952, 934, 805 cmÀ1; Ru:
(0.0174 mmol/g).
[7] Q. Yao, Angew. Chem. Int. Ed. 2000, 39, 3896–3898.
[8] a) M. Zaja, S. J. Connon, A. M. Dunne, M. Rivard, N.
Buschmann, J. Jiricek, S. Blechert, Tetrahedron 2003,
59, 6545–6558; b) S. J. Connon, M. Rivard, M. Zaja, S.
Blechert, Adv. Synth. Catal. 2003, 345, 572–575.
[9] A. Michrowska, R. Bujok, S. Harutyunyan, V. Sashuk, G.
Dolgonos, K. Grela, J. Am. Chem. Soc. 2004, 126, 9318–
9325.
[10] a) H. Wakamatsu, S. Blechert, Angew. Chem. Int. Ed.
2002, 41, 2403–2405; b) A. M. Dunne, S. Mix, S. Ble-
chert, Tetrahedron Lett. 2003, 44, 2733–2736; c) N.
Buschmann, H. Wakamatsu, S. Blechert, Synlett 2004,
4, 667–670.
Acknowledgements
We thank the Fonds der chemischen Industrie“ and the Gra-
duiertenkolleg ”Synthetische, mechanistische und reaktion-
stechnische Aspekte von Metallkatalysatoren“ for financial sup-
port; Verena Boehrsch for silica gel and Dr. Simon Maechling
for helpful discussions.
[11] Purchased from Merck; specifications LiChroprep Si 60ꢁ
40–63 mm: specific surface area 460–580 m2/g, pore vol-
ume 0.70–0.90 mL/g, particle size 40–63 mm; specifica-
tions LiChroprep Si 60ꢁ 25–40 mm: specific surface
area 480–540 m2/g, pore volume 0.74–0.84 mL/g, parti-
cle size 25–40 mm.
References and Notes
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[1] Grubbs catalyst refers to benzylidenebis(tricyclohexyl-
¼
phosphine)dichlororuthenium, RuCl2(PCy3)2 CHPh.
[2] Grubbs–Herrmann catalyst refers to benzylidene-1,3-
[bis-(2,4,6-trimethylphenyl)-imidazolidinylidene]dichloro-
(tricyclohexylphosphine)ruthenium; RuCl2PCy3H2IMes
CHPh.
[3] R. H. Grubbs, Handbook of Metathesis, Wiley-VCH,
London, 2003, Vols 1–3.
[4] a) S. Gessler, S. Randl, S. Blechert, Tetrahedron Lett.
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7b with ethyl vinyl ether/triphenylphosphine in dichloro-
methane to detach the (pre)catalyst and measure the
content of ruthenium in the filtrate quantitatively by to-
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P. Rostam-Khani, M. Mertens, C. Rittmeyer, B. O.
Kolbesen, Totalreflexions-Rçntgenfluorenszenzanalyse
(TXRF). Eine vielfältig einsetzbare Methode zur Mikro-,
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und Biotechnik, 48. Jahrgang, 12, 506, 1997.
¼
[14] M. Zaja, Ph. D. thesis, TU Berlin, 2005.
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