A new stable Hoveyda-Grubbs catalyst with mixed anionic ligands

Article abstract of DOI:10.1016/j.tetlet.2006.09.096

The synthesis and characterisation of a new highly active Hoveyda-Grubbs 2nd generation type catalyst is described. Substitution of one chloride ligand with a partially fluorinated trialkoxysilyl substituted carboxylate leads to the stable monocarboxylate

Full text of DOI:10.1016/j.tetlet.2006.09.096

Tetrahedron Letters 47 (2006) 8617–8620
A new stable Hoveyda–Grubbs catalyst with mixed anionic ligands
a,b
a
b,
a,
*
Kati Vehlow, Simon Maechling, Katrin K o¨ hler and Siegfried Blechert
a
Technische Universit a¨ t Berlin, Strasse des 17. Juni 135, 10623 Berlin, Germany
b
Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
Received 25 August 2006; revised 18 September 2006; accepted 19 September 2006
Available online 16 October 2006
Abstract—The synthesis and characterisation of a new highly active Hoveyda–Grubbs 2nd generation type catalyst is described.
Substitution of one chloride ligand with a partially fluorinated trialkoxysilyl substituted carboxylate leads to the stable monocarb-
oxylate ruthenium catalyst (3). This catalyst represents the first example of a stable and isolable mono-chloride exchanged carboxy-
late complex suitable for both homogeneous and heterogeneous metathesis. The reactivity of the new catalyst was tested in
representative metathesis reactions and offers an activity comparable to the parent dichloride system (1).
Ó 2006 Elsevier Ltd. All rights reserved.
In the field of olefin metathesis, ruthenium based car-
bene complexes play an outstanding role. In particular,
the ruthenium (pre)catalysts Grubbs 2nd generation
During our studies on the synthesis of a homogeneous
ruthenium catalysts, which could potentially be immobi-
lised on silica gel, we discovered a highly selective
mono-substitution of one chloride ligand. This has made
possible the direct comparison between mono- and
dicarboxylate substituted catalysts and their parent
dichloride systems concerning reactivity and stability.
1
[
RuCl (@CH–C H )(PCy )(SIMes)] (SIMes = 1,3-bis(2,4,6-
2
6
5
3
trimethylphenyl)-4,5-dihydroimidazol-2-ylidene)
and
the Hoveyda–Grubbs 2nd generation [RuCl (@CH-o-
2
O–i-Pr–C H )(SIMes)] (1) represent reagents of choice
6
4
for a variety of applications in organic chemistry. Dur-
ing the last few years the modification of ligands have
led to metathesis (pre)catalysts with specific characteris-
tics. The variation of the halogen ligands was first exam-
The required silver carboxylate (EtO) Si–C H –NH–
3
3
6
CO–C F –COOAg (2) was readily synthesised accord-
3
6
8
ing to the described literature procedure. Initial studies
were concerned with monosubstitution of one chloride
ligand of 1 with silver carboxylate 2 (Scheme 1). Previ-
ous attempts to synthesise similar trifluoroacetate
2
ined by Grubbs and co-workers Later the replacement
3
7c
of the chloride ligands by alkoxides, dicarboxylates,
2
a
trifluoroacetates and other strong electron-withdraw-
ing fluorocarboxylates, as well as fluorosulfonates
4
,5
4a
was also investigated. Substitution of the anionic ligands
was also used for the immobilisation of Grubbs 2nd
generation and Hoveyda–Grubbs 1st and 2nd genera-
tion-type catalysts.4
,6,7
However, there are only a few
known cases of homogeneous Grubbs and Hoveyda–
7
c,4a
Grubbs catalysts with mixed anionic ligands.
Typi-
cally, the exchange with fluorocarboxylates does not
lead to clean monosubstitution. Only nonseparable
mixtures of the reactants, bis- and monoadducts could
be isolated. Therefore the reactivity of these mixed anio-
nic compounds is more or less unknown.
Keywords: Carboxylate ligands; Metathesis; Ruthenium; Catalysis.
*
Corresponding author. Fax: +49 303 31423619; e-mail: blechert@
chem.tu-berlin.de
New address: Sartorius AG, Weender Landstrasse 94-108, 37075
G o¨ ttingen, Germany.
Scheme 1. Synthesis of 3, 4 and 6.
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.09.096

8618
K. Vehlow et al. / Tetrahedron Letters 47 (2006) 8617–8620
0
a
Table 1. RCM of N,N -diallyltosylamide (7)
high purity as a violet powder, by the reaction of 1 with
equiv of silver carboxylate 2 (Scheme 1).
2
In order to investigate the influence of the alkoxysilyl
group on the observed monosubstitution we reacted
1
equiv of 1 with 1 equiv of the alkoxysilyl-free (iPr) N–
2
b
Entry
Cat.
Loading (mol %)
Conv. (%)
TON
8
CO–C F –COOAg (5) (Scheme 1).
3
6
1
2
3
4
5
6
1
1
3
3
4
4
0.01
0.02
0.01
0.02
0.01
0.02
49
66
51
66
27
39
4860
3300
5050
3290
2690
1970
Utilisation of THF in place of CH Cl afforded the
2
2
olive-green complex 6 in 92% yield as an inseperable
mixture of 92% of 6, 4% of the disubstituted catalyst
and 4% of 1. The silyl-free mono-carboxylate complex
6
was found to be unstable in solution, especially in
a
Conditions: 0.05 M solution of 7, CH
Conversions were determined by HPLC.
2
Cl
2
, 45 °C, 14 h.
chlorinated solvents and disproportionated. From these
results we tentatively assign the stability of 3 to a stabil-
ising Ru–Si(OEt) interaction. This kind of interaction
has been also observed for the trialkoxysilyl-functional-
b
8
derived mono-substituted catalysts, have been met with
limited success, affording only an inseparable mixture of
products including mono- and di-substituted complexes
ised silver(I)-carboxylates.
With the pure complexes 1, 3 and 4 in hand we were
interested in their relative reactivity in the ring closing
metathesis (RCM). A meaningful comparison of the
activity between the different catalysts can be achieved
by determining the turnover numbers (TONs) at the
4
a
and starting material.
We observed that it was possible to achieve a clean con-
version to the monosubstituted derivative 3 by utilising
a partially fluorinated trialkoxysilyl substituted silver
carboxylate. When 1 was treated with 1 equiv of silver
carboxylate 2 in CH Cl , complex 3 could be isolated
1
0
same catalyst loading. Therefore, we tested the three
0
catalysts in the RCM of N,N -diallyltosylamide (7)
2
2
(Table 1).
9
in high purity as an olive green powder, in 82% yield.
Following a similar protocol, both chloro-ligands could
As can be seen from Table 1, the reactivity of the mono-
be substituted in a clean reaction and 4 was isolated in
carboxylate complex 3 rivalled with the parent catalyst
a
Table 2. Representative metathesis reactions utilising 3
b
b
c
Entry
1
Substrate
Product
Conv. (E:Z) (%)
Time (h)
2
Loading (mol %)
0.5
>99
2
>99
1
0.5
3
4
>95
>95
1
3
0.5
0.5
5
6
>99
>99
3
2
0.5
0.5

K. Vehlow et al. / Tetrahedron Letters 47 (2006) 8617–8620
8619
Table 2 (continued)
b
b
c
Entry
Substrate
Product
Conv. (E:Z) (%)
Time (h)
6
Loading (mol %)
1
7
35
8
9
77 (8:1)
>99 (only E)
73 (1:4)
12
12
3
3
3
5
1
0
a
b
c
All reactions were performed in refluxing CH
E@CO Et.
Conversions determined by H NMR.
2 2
Cl .
2
1
1
4
. In contrast the reactivity of the dicarboxylate catalyst
is clearly reduced.
at other ruthenium systems as well as immobilisation
is in progress.
Finally, the activity of 3 was tested in a series of meta-
thesis reactions and the results are summarised in Table
Acknowledgements
2
. It is clear to see that 3 is capable of performing a
variety of metathesis reactions.
We are grateful to the analytical department of Merck
KGaA for NMR, IR and GF-AAS spectroscopic
measurements and C, H and N analyses and the
Graduiertenkolleg ‘Synthetische, mechanistische und
reaktionstechnische Aspekte von Metallkatalysatoren’
for financial support.
Catalyst 3 showed a high activity at a low catalyst load-
ing (0.5 mol %) for RCM (entries 1–4), including a more
sterical substrate (entry 1). Entries 5 and 6 represent
examples of metathesis sequences; that is, ring re-
arrangement metathesis (RRM) and ring opening cross
metathesis (ROM/CM) respectively. Starting from the
endo-educts, the corresponding products were formed
in high yields (>99%), using only 0.5 mol % catalyst.
Another useful feature is the highly selective cross-
metathesis (entries 8 and 9) yielding the products in high
yield as would generally be expected. And also the elec-
tron-poor acrylonitrile may be used for CM in a good
yield (73%) at 5 mol % catalyst loading (entry 10).
Although for enyne metathesis (entry 7) 3 performed
poorly offering only 35% conversion after 6 h.
References and notes
1
. Selected reviews: (a) Grubbs, R. H.; Miller, S. J.; Fu, G. C.
Acc. Chem. Res. 1995, 28, 446; (b) Schmalz, H.-G. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1833; (c) Schuster, M.;
Blechert, S. Angew. Chem., Int. Ed. 1997, 36, 2036; (d)
F u¨ rstner, A. Top. Catal. 1997, 4, 285; (e) Armstrong, S. K.
J. Chem. Soc., Perkin Trans. 1 1998, 371; (f) Grubbs, R.
H.; Chang, S. Tetrahedron 1998, 54, 4413; (g) F u¨ rstner, A.
Angew. Chem., Int. Ed. 2000, 39, 3012; (h) Trnka, T. M.;
Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18; (i) Handbook
of Olefin Metathesis; Grubbs, R. H., Ed.; VCH-Wiley:
Weinheim, Germany, 2003; (j) Schrock, R. R.; Hoveyda,
A. H. Angew. Chem., Int. Ed. 2003, 42, 4592; (k) Grubbs,
R. H. Tetrahedron 2004, 60, 7117.
In summary, we present a stable and isolable monocarb-
oxylate ruthenium metathesis complex (3). This (pre)cat-
alyst is functionalised with one partially fluorinated
trialkoxysilyl carboxylate. The synthesis of the disubsti-
tuted catalyst 4 allows a direct comparison between
mono- and disubstitution concerning reactivity and sta-
bility. Compound 3 shows similar activity in RCM of 7
compared to the parent dichloride system (1), mean-
while the reactivity of 4 is significantly lower. Further-
more, catalyst 3 displays an excellent activity for
various metathesis reactions, even at low catalyst load-
ing. Investigation of the selectivity chloride exchange
2
. (a) Wu, Z.; Nguyen, S. T.; Grubbs, R. H.; Ziller, J. W. J.
Am. Chem. Soc. 1995, 117, 5503; (b) Dias, E. L.; Nguyen,
S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1997, 119, 3887;
(
c) Lynn, D. M.; Mohr, B.; Grubbs, R. H.; Henling, L.
M.; Day, M. W. J. Am. Chem. Soc. 2000, 122, 6601; (d)
Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem.
Soc. 2001, 123, 6543; (e) Seiders, T. J.; Ward, D. W.;
Grubbs, R. H. Org. Lett. 2001, 3, 3225; (f) Funk, T. W.;

8620
K. Vehlow et al. / Tetrahedron Letters 47 (2006) 8617–8620
Berlin, J. M.; Grubbs, R. H. J. Am. Chem. Soc. 2006, 128,
480.
. (a) Sanford, M. S.; Henling, L. M.; Day, M. W.; Grubbs,
R. H. Angew. Chem., Int. Ed. 2000, 39, 3451; (b) Coalter,
J. N.; Bollinger, J. C.; Eisenstein, O.; Caulton, K. G. New
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. (a) Krause, J. O.; Nuyken, O.; Wurst, K.; Buchmeiser, M.
R. Chem. Eur. J. 2004, 10, 777; (b) Krause, J. O.; Nuyken,
O.; Buchmeiser, M. R. Chem. Eur. J. 2004, 10, 2029; (c)
Yang, L.; Mayr, M.; Wurst, K.; Buchmeiser, M. R. Chem.
Eur. J. 2004, 10, 5761; (d) Halbach, T. S.; Mix, S.; Fischer,
D.; Maechling, S.; Krause, J. O.; Sievers, C.; Blechert, S.;
Nuyken, O.; Buchmeiser, M. R. J. Org. Chem. 2005, 70,
2 2
(100.0 mg, 159.6 lmol, 1 equiv) in dry CH Cl (10 ml).
1
While stirring was continued for 60 min a white disperse
precipitate formed. The precipitate was filtered and the
filtrate was evaporated to dryness. The residue was
dissolved in CH Cl (2 ml) and n-hexane (6 ml) added.
2 2
The precipitate was removed by filtration and the solvent
was removed in vacuo. Drying under high vacuum
3
4
afforded 135.3 mg (130.9 lmol, 82.0%) of a olive green
1
powder. H NMR (250 MHz, CD
2
Cl
2
): d 17.14 (s, 1H,
CH = Ar), 7.48 (dt, J = 7.8 Hz, 1.8 Hz, 1H, aromat. CH),
7.17, 7.07 (s, 4H, mes.-CH), 7.02 (dd, J = 7.5 Hz, 1.8 Hz,
1H, aromat. CH), 6.94 (t, J = 7.1 Hz, 1H, aromat. CH),
6.76 (br s, 1H, NH), 6.76 (d, J = 8.3 Hz, 1H, aromat. CH),
4.69 (septet, J = 6.1 Hz, 1H, i-Pr–CH), 4.14 (s, 4H,
4687.
5
6
7
. (a) Conrad, J. C.; Amoroso, D.; Czechura, P.; Yap, G. P.
A.; Fogg, D. E. Organometallics 2003, 22, 3634; (b)
Conrad, J. C.; Parnas, H. H.; Snelgrove, J. L.; Fogg, D. E.
J. Am. Chem. Soc. 2005, 127, 11882; (c) Conrad, J. C.;
Snelgrove, J. L.; Eeelman, M. D.; Hall, S.; Fogg, D. E.
J. Mol. Catal. A: Chem. 2006, 254, 105.
. (a) Buchowicz, W.; Mol, J. C.; Lutz, M.; Spek, A. L. J.
Organomet. Chem. 1999, 588, 205; (b) Buchowicz, W.;
Ingold, F.; Mol, J. C.; Lutz, M.; Spek, A. L. Chem. Eur. J.
imidazole–CH
3.20 (q, J = 6.7 Hz, 2H, CH
3 3
CH ), 2.43 (s, 6H, mes.-p-CH ), 2.25 (s, 6H, mes.-o-CH
2
), 3.80 (q, J = 7.0 Hz, 6H, Si–OCH
2
),
2
NH), 2.46 (s, 6H, mes.-o-
3
),
1.57 (m, 2H, Si–CH –CH ), 1.21 (t, J = 7.0 Hz, 9H, Si–
2
2
OCH
3H, i-Pr–CH
(235 MHz, CD Cl ): d ꢀ124.5, ꢀ124.3 (2s, 2F, CF ),
2
–CH ), 1.02 (d, J = 6.1 Hz, 3H, iPr–CH ), 0.98 (m,
3
3
19
3 2
), 0.57 (t, J = 8.0 Hz, 2H, SiCH ). F NMR
2
2
2
ꢀ119.7, ꢀ119.4 (2t, 2F, CF CONH), ꢀ115.1, ꢀ114.8 (dt,
2
1
3
2 2 2
t, 2F, CF COORu). C NMR (75.5 MHz, CD Cl ): d
2
001, 7, 2842; (c) Nieczypor, P.; Buchowicz, W.; Meester,
W. J. N.; Rutjes, F. P. J. T.; Mol, J. C. Tetrahedron Lett.
001, 42, 7103.
307.4 (CH@Ar), 210.7 (imidazole–N–C–N), 161.3 (COO),
158.7 (CONH), 153.4 (aromat. C), 144.6 (aromat. C),
139.6 (mes.-p-C), 139.5, 139.1 (mes.-o-C), 135.7 (mes.-C–
N), 130.3 (aromat. CH), 129.9 (mes.-CH), 123.0 (aromat.
CH), 122.7 (aromat. CH), 112.7 (aromat. CH), 111.3
(CF CONH), 109.7 (CF COORu), 108.1 (CF ), 75.6 (i-
2
. (a) Krause, J. O.; Lubbad, S.; Nuyken, O.; Buchmeiser,
M. R. Macromol. Rapid Commun. 2003, 24, 875; (b)
Krause, J. O.; Zarka, M. T.; Anders, U.; Weberskirch, R.;
Nuyken, O.; Buchmeiser, M. R. Angew. Chem., Int. Ed.
2
2
2
Pr–CH), 58.9 (SiOCH
2
), 51.9 (imidazole–CH
2
),
),
2003, 42, 5965; (c) Krause, J. O.; Lubbad, S.; Nuyken, O.;
42.5(CH NH), 22.7 (Si–CH –CH ), 21.3 (mes.-p-CH
2
2 2
3
Buchmeiser, M. R. Adv. Synth. Catal. 2003, 345, 996.
. Vehlow, K.; K o¨ hler, K.; Blechert, S.; Dechert, S.; Meyer,
F. Eur. J. Inorg. Chem. 2005, 2727.
. Synthesis of the catalysts was performed under an argon
atmosphere by standard Schlenk techniques or in an
Argon-mediated dry-box (Labmaster 130, Mbraun, Ger-
many). Solvents were dried before use, employing stan-
20.5 (i-Pr–CH ), 19.2 (br s, mes.-o-CH ), 18.7 (mes.-o-
CH ), 18.5 (Si–OCH –CH ), 8.0 (Si–CH ). IR (KBr): m
3 2 3 2
3072 (w), 2976 (m), 2925 (m), 2895 (w), 1772 (w), 1717
(vs), 1700 (vs), 1592 (w), 1577 (w), 1540 (m), 1482 (m),
1455 (m), 1399 (w), 1387 (m), 1377 (w), 1355 (w), 1297 (w),
1266 (s), 1215 (w), 1157 (vs), 1113 (s), 1100 (s), 1078 (s),
1038 (w), 940 (m), 851 (w), 841 (m), 798 (m), 749 (m). EA
3
3
8
9
dard drying agents. [RuCl((EtO)
3
Si–C
H
3 6
–NH–CO–
6 3 7 2
for C45H60ClF N O RuSi (1033.573) (found (calcd.)): C
C F –COO) (@CH–o-O–i-Pr–C H )(SIMes)] (3): A solu-
52.2 (52.29), H 5.9 (5.85), N 4.0 (4.07).
10. Maechling, S.; Zaja, M.; Blechert, S. Adv. Synth. Catal.
2005, 347, 1413.
3
6
6
4
tion of 2 (100.4 mg, 159.6 lmol, 1 equiv) in dry CH
2 2
Cl
(
40 ml) was slowly added to a stirred solution of 1