Monolithic disk-supported metathesis catalysts for use in combinatorial chemistry

Article abstract of DOI:10.1002/adsc.200404197

Two metathesis catalysts, RuCl₂(PCy₃)-(NHC)(CHPh) (1) [NHC = 1-(2,4,5-trimethylphenyl)-3-(6-hydroxyhexyl)-imidazol-2-ylidene] and Mo(N-2,6-i-Pr₂-C₆H₃)(CHCMe₂Ph) (BIPHEN) (2) [BIPHEN = -3

Full text of DOI:10.1002/adsc.200404197

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Monolithic Disk-Supported Metathesis Catalysts for Use in
Combinatorial Chemistry
a
a
a
a
b
Monika Mayr, Dongren Wang, Roswitha Krçll, Norbert Schuler, Stefan Prꢀhs,
b
a,
Alois Fꢀrstner, Michael R. Buchmeiser *
Leibniz Institut fꢀr Oberflꢁchenmodifizierung (IOM) e. V., Permoserstr. 15, 04318 Leipzig, Germany, and Technische
a
Chemie der Polymere, Universitꢁt Leipzig, Linn e´ str. 3, 04103 Leipzig, Germany
Fax: (þ49)-341-235-2584, e-mail: michael.buchmeiser@iom-leipzig.de
b
Max-Planck-Institut fꢀr Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mꢀlheim a.d. Ruhr, Germany
Fax: (þ49)-208-306-2994, e-mail: fuerstner@mpi-muelheim.de
Received: June 24, 2004; Accepted: November 2, 2004
th
Dedicated to Prof. Richard R. Schrock, a brilliant scientist, scholar and friend on the occasion of his 60 birthday.
Abstract: Two metathesis catalysts, RuCl (PCy )- Monolithic disc-immobilized 2 was used in various
2
3
(
NHC)(CHPh) (1) [NHC¼1-(2,4,5-trimethylphen- enantioselective RCM and desymmetrization reac-
yl)-3-(6-hydroxyhexyl)-imidazol-2-ylidene]
Mo(N-2,6-i-Pr -C H )(CHCMe Ph)(BIPHEN)
and tions. Using 9–13 mol % of supported catalyst, excel-
(2) lent yields up to 100% and high enantiomeric excess
(eeX88%) were observed. In both cases, metal leach-
2
6
3
2
[
2
BIPHEN¼(R)-3,3’-di-t-butyl-5,5’,6,6’-tetramethyl-
,2’-biphenolate) have been immobilized on polymer- ing was low (X3 and X2%, respectively). In addition,
ic, monolithic discs using a “grafting from” protocol. 1 catalyzed the cyclopolymerization of diethyl dipro-
Monolithic discs were prepared via ring-opening pargylmalonate (DEDPM) to yield poly(ene)s consist-
metathesis polymerization (ROMP) from norborn-2- ing of 5-membered rings, i.e., cyclopent-1-ene-1-vinyl-
ene (NBE), tris(norborn-5-ene-2-ylmethyleneoxy)- ene units. The polymerization proceeded via non-stoi-
methylsilane [(NBE-CH O) -SiCH ], 2-propanol, tol- chiometric initiation yielding polymers with unimodal
2
3
3
uene and RuCl (PCy ) (CHPh). Catalyst loadings of molecular weight distribution. Using a catalyst to mon-
2
3 2
0
.55 and 0.7 wt %, respectively, were obtained. Mon- omer ratio of 1:170, molecular weights of M ¼16,400
w
olithic disc-immobilized 1 was used in various meta- and M ¼11,700 g/mol, PDI¼1.40 were obtained.
n
thesis-based reactions including ring-closing metathe-
sis (RCM), ring-opening cross metathesis and enyne Keywords: heterogeneous catalysis; high throughput
metathesis. Using 0.23–0.59 mol % of supported 1, screening; metathesis; molybdenum; polymers; ruthe-
turnover numbers (TONs) up to 330 were achieved. nium
Introduction
For obvious reasons, there is an increasing demand for
supported versions of these metathesis catalysts.
[17–30]
The success story of metathesis reactions in both organic First, contaminationofproductswithmetalionsand/orli-
and polymer chemistry is strongly related to the devel- gandsneedstobelow, particularlyincompoundsrelevant
opment of suitable, highly active and selective catalytic to pharmaceutical chemistry. Second, modern metathesis
systems. In this context, both molybdenum-based catalysts significantly add to the total costs of a product,
[
1–4]
Schrock catalysts
alysts
and ruthenium-based Grubbs cat- therefore regeneration and/or reuse are highly desirable.
[
5–8]
with all their structural variations define the And third, supported catalysts offer access to high-
standard in the field. With the large number of par- throughput techniques and continuous flow reactors, re-
ticularly designed catalytic systems in hand, one can spectively. Therefore, the key issues relevant for support-
now accomplish an almost unlimited range of metathe- ed metathesis catalysts are (i) preservation of activity,
[
9–13]
sis-based CꢀC coupling reactions.
Moreover, recent (enantio-) selectivity and reaction rate observed with
outstanding achievements made in the area of asymmet- the parent homogeneous system, (ii) ease of catalyst sep-
ric metathesis have opened the door to a large variety of aration, (iii) (multiple) catalyst recycling, and (iv) forma-
enantiomerically pure cyclic and oligocyclic structures, tion of metal- and contaminant-free products.
e.g., for pharmaceutical, medical and health-care appli-
cations.
In course of ongoing projects on supported Grubbs
[4,14–16]
[18,31–36]
and Schrock catalysts,
we investigated the immo-
484
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Figure 1. Structures of 1 and 2.
bilization of a new version of Grubbsꢃ catalyst (1), re-
[
22,37]
cently reported by Fꢀrstner et al.,
as well as of a chi-
on a monolithic
[
29,30]
ral version of Schrockꢃs catalyst (2)
support (Figure 1).
Additionally, and in contrast to previously reported
Scheme 1. Acetylation of 1.
[
18,31–35,38]
monolith-immobilized catalytic systems,
we fo-
cused on the development of disc-shaped monolithic
[
28]
systems applicable to high-throughput screening rath- to the rearrangement of the catalyst. Therefore, PCy3
er than on previously published monolithic supports de- was used as base in the reaction of 1 with acetyl chloride
signed for continuous flow applications.
for both the removal of HCl and the structural preserva-
tion of 1 (Scheme 1).
Applying reaction conditions identical to those used
Results and Discussion
for heterogenization (1.5 hours, 258C, CDCl , vide in-
3
fra), the disappearance of the signal at d¼3.62 ppm
(
4
CH OH) and the appearance of a new signal at d¼
2
Synthesis of Monolith-Immobilized 1
.06 ppm (m, CHCOOCH ) was observed. The alkyli-
2
dene signal at d¼19.23 ppm remained unchanged.
Monolithic supports were prepared from norborn-2-ene Due to the overlap with resonances of the PCy
3
(
NBE), tris(norborn-5-ene-2-ylmethyleneoxy)methyl-
group, the resonance for the acetyl group could not
silane [(NBE-CH O) -SiCH ], 2-propanol, toluene and unambiguously be assigned. For the immobilization of
2
3
3
RuCl (PCy ) (CHPh) using the ring-opening metathe- 1, a solution of norborn-5-ene-2-carboxylic chloride in
2
3 2
sis polymerization (ROMP) based protocol developed CH Cl was passed over the support and graft-polymer-
2
2
[
39–46]
by our group.
A 1:1 ratio (by weight) of NBE and ization was allowed to proceed overnight (Scheme 2).
The catalyst and unreacted monomer were removed
the cross-linker (NBE-CH O) -SiCH and a weight frac-
2
3
3
tion of 40 wt % of these two monomers with respect to by washing the support with a solution of ethyl vinyl
the entire polymerization mixture were chosen through- ether in CH Cl . Finally, a mixture of 1 and PCy in
2
2
3
out. This ratio and weight fraction led to the formation CH Cl was added. Following this protocol, a loading
2
2
of a monolithic structure with roughly 67% interparticle of 0.55 wt % of 1 on the monolithic support was ach-
porosity. Such a high porosity was necessary for two rea- ieved. The monolith was dried, removed from the car-
sons. First, it provided enough free volume for the graft- tridge, cut in pieces of 0.5 cm thickness and encased.
ing of the monomer of interest. Second, no clogging of Such encased monolithic discs simultaneously served
the monolithic support was observed, either during syn- as support, reaction vessel and filtration unit. Once a
thesis or during use. For monolith manufacture, NBE proper encasement is performed, one can in principle
and the cross-linker were dissolved in 2-propanol and use such systems in commercially available machines
a solution of RuCl (PCy ) (CHPh) in toluene was add- for combinatorial chemistry and high-throughput
2
3 2
ed. The mixture was placed inside a suitable column screening, respectively. For the present investigations,
and polymerization was allowed to proceed for 25 mi- poly(ethylene) and glass syringes, respectively, were
nutes at 08C and a further 25 minutes at room tempera- used. Nevertheless, these could still be assembled in a
ture. After careful washing of the monolith with toluene way that the reactions of interest can be run simultane-
and CH Cl , the active, surface-immobilized catalyst ously under identical and defined conditions.
2
2
moieties were used for surface derivatization.
Prior to that, suitable heterogenization conditions had
1
to be elaborated. In a H NMR experiment, 1 was treat- Catalytic Performance of Monolith-Bound 1
ed with excess acetyl chloride in the presence of pyridine
and tricyclohexylphosphine (PCy ), respectively. Fꢀrst- In order to get additional information on the reactivity
3
[22]
[22]
ner et al. reported that addition of pyridine to 1 leads of 1, it was used in various standard metathesis-based
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Scheme 2. Synthesis of monolithic discs and immobilization of 1.
reactions. As can be deduced from Table 1 and from the ored polymer was observed. In order to gain more infor-
[
22]
data reported in the literature, 1 is a catalyst with mation on the polymerization characteristics of this cat-
moderate activity, allowing turnover numbers (TONs) alyst, free 1 was used to prepare poly(DEDPM). Cyclo-
in the range of 60–550 using 0.1–0.05 mol % of catalyst. polymerization of this monomer proceeded rapidly both
With the supported version of 1, TONs obtained in the at room temperature and at 408C, producing a deep red-
1
3
ring-closing metathesis (RCM) of diethyl diallylmalo- violet polymer in 60% yield. Its C NMR spectrum re-
nate (DEDAM), 1,7-octadiene, tert-butyl-N,N-diallyl- vealed the presence of one single repetitive units, i.e.,
carbamide and N,N-diallytrifluoroacetamide were in poly(cyclopent-1-ene-1-vinylene)s as evidenced by the
[
47,48]
the range of 60–330 and are comparable to those ob- chemical shift of 171.6 ppm,
tained with the parent system 1 (Table 1).
for the carbonyl carbon
1
3
of the repetitive unit in the C NMR spectrum. The 5-
A significantly lower TON compared to the homoge- membered ring content was>95%. It is worth mention-
neous reaction (40 vs. 100) was obtained in the ring- ing that this is the first ruthenium-catalyzed cyclopoly-
opening cross metathesis reaction of 7-oxanoroborn-5- merization of DEDPM with a ruthenium catalyst con-
ene-2,3-dicarboxylic anhydride with allyltrimethylsi- taining an unsaturated N-heterocyclic carbene. All other
lane. These differences are rather attributed to the dif- cyclopolymerizations carried out with ruthenium-based
ferent reaction conditions applied here, i.e., an unstirred initiators so far required the presence of saturated N-
[
49–52]
vs. stirred batch, than to a restricted access of the sub- heterocyclic carbenes.
Unfortunately, the polymer-
strates to the polymer-bound catalyst. In all cases, Ru- ization of DEDPM proceeded in a non-stoichiometric
leaching was X3%, the average contamination of prod- manner, yet yielding polymers with a unimodal mo-
ucts with ruthenium was around 70 ppm. It is worth not- lecular weight distribution. Thus, GPC traces of poly(-
ing that the catalyst-containing monolithic discs were DEDPM) prepared from 1 and DEDPM with a catalyst
designed as “one-way” discs, therefore no recycling or to monomer ratio of 1:170 showed molecular weights of
multiple use was attempted.
M ¼16,400 and M ¼11,700, respectively, indicating
w
n
Interestingly, enyne metathesis carried out with dieth- significant chain transfer. In this case, additional unfav-
yl dipropargylmalonate (DEDPM) and allyltrimethylsi- orable ratios of k /k cannot be excluded. The UV-VIS
i
p
lane led exclusively to the formation of poly(DEDPM). spectra of the polymers showed an absorption maximum
No product originating from enyne metathesis, yet high at lmax ¼535 nm with an additional shoulder at l
¼
max
conversion of DEDPM and formation of a deeply col- 575 nm (in CHCl ).
3
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Table 1. Summary of RCM, ring-opening cross metathesis and enyne metathesis reactions performed with free 1 and mono-
lith-bound 1, respectively.
Substrate
Product
Mol %
Yield [%]
TON
Mol %
immobilized
Yield
[%]
TON
1
/time [h]
1
/time [h]
[
c]
16[
[c]
0
0
.1 /3.5
160
190
0.47 /2.8
29
98
60
200
22]
DEDAM
[
22]
95
[22]
[e]
.5/24
0.5/24
[
d]
[d]
[f]
1
,7-octadiene
cyclohexene
0.1 /3.5
55
18
550
180
0.23 /3.5
75
330
130
[
c]
[c]
tert-butyl-N,N-diallylcarbamide
N,N-diallyltrifluoro-acetamide
0.1 /3.5
0.41 /2.8
54
73
[c]
0
0
.25 /3.5
.49 /3.5
14
40
60
70
[c]
0.48 /2.8
150
40
–
[c]
[
d]
[d]
1
.0 /5.5
>95
100
–
1.4 /4
50
–
polymer
–
polymer
All reactions were run at 458C.
[a]
[b]
[c]
[d]
[e]
[f]
Catalyst 1.
Monolith-immobilized 1.
CH Cl .
2
2
CHCl3.
[22]
Silica-immobilized version described by Fꢀrstner et al.
Polymer formed.
Synthesis of Monolith-Immobilized 2
(CHCMe Ph)(OTf) ·DME. Following this protocol, a
2 2
loading of 0.7 wt % of 2 on the monolithic support was
asymmetric metathesis reac- achieved. Similar to the protocol described for mono-
tions that require high enantiomeric excess (ee) are still lith-immobilized 1, the monolith loaded with 2 was cut
[
11,53]
With a few exceptions,
[
54–66]
a domain of molybdenum-based Schrock initiators.
in pieces 1 cm in height and encased using SPE syringes.
So far, there exist only few reports on the immobiliza- Alternatively, encasement may be performed in a way
tion of chiral Schrock catalysts. The supported systems that polymer-encased membranes, which may directly
reported so far were either prepared via free radical pol- be used as reaction vessels/filtration units in commer-
[29]
ymerization or ring-opening metathesis precipitation cially available machines for parallel synthesis and
[36]
polymerization. In order to immobilize 2 on a mono- high-throughput screening (HTS), respectively, are ob-
lithic support, a similar protocol as was used for the im- tained (Figure 2).
mobilization of 1 was applied. After rod formation was
complete and unreacted monomer had been removed
from the support, a polymerizable analogue of BI- Catalytic Performance of Monolith-Bound 2
PHEN, (R)-5,5’-bis-(norborn-5-ene-2-ylmethyleneoxy-
[
29]
methyl)-3,3’-di-t-butyl-6,6’-dimethylbiphen-2,2’-diol,
Enantioselective RCM was carried out with monolith-
was grafted to the surface (Scheme 3).
bound 2 using the substrates summarized in Table 2. Us-
In contrast to molybdenum-initiated polymeriza- ing 9–13 mol % of catalyst, yields were virtually quanti-
[36]
tions, no protection of the free phenolic groups was tative throughout.
[36]
necessary. The grafted phenolic moieties were depro-
For 3-allyloxy-2,4-dimethylpenta-1,4-diene and 2,4-
tonated by adding KN[Si(CH ) ] and subsequently re- dimethyl-3-(dimethylvinylsilyloxy)-penta-1,4-diene
3
3 2
acted with the catalyst precursor Mo(N-2,6-i-Pr -C H )- (Table 2, entries 1 and 2), the enantiomeric excess (ee)
2
6
3
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Table 2. Summary of asymmetric RCM and desymmetrization reactions performed with monolith-bound 2.
Entry
Educt
Product
Mol % catalyst
Yield [%]
ee [%]
[
36]
[29] [a]
1
11
99
79 (90, 89
)
[
36] [a]
2
3
9
95
99
88 (95
)
[
36]
[58] [a]
13
43 (90, 89
)
[
36] [a]
4
5
6
9
13
13
>99
4 (25
)
[
36]
[55] [b]
75
43ꢁ5 (53, 47
)
[
36]
[55] [c]
99
45ꢁ5 (50, 45
)
[a]
[b]
[c]
Separated by GC.
Mobile phase: 70% buffer (0.1 M triethylamine, acetic acid, pH¼4), 30% mix (80% acetonitrile, 20% water).
Mobile phase: heptane:2-propanol (99: 1). Unless stated otherwise, all r.s.d.ꢃs were ¼2%.
was comparable to that achieved with other immobi- within the monolithic support. However, N-allyl-N-(2-
lized versions of 2. 2,4-Dimethyl-3-(dimethylvinylsilyl- methyl-4-phenylbut-1-en-4-yl)aniline and N-(isobut-1-
oxy)-penta-1,4-diene and particularly 3-allyloxy-3-phe- en-3-yl)-N-(4-phenylbut-1-en-4-yl)aniline were con-
nylisobut-1-ene (Table 2, entries 3 and 4) showed signif- verted in 75 and 99% yield, respectively (Table 2, entries
icantly reduced ees of 43 and 4% (compared to 90 and 5 and 6). The ees found were slightly lowered, yet similar
25%, respectively). So far, we cannot explain this drop to those reported with other systems. In all cases, con-
in ee, yet tentatively attribute it to geometric constraints tamination of products with molybdenum was <2 wt %.
Figure 2. Encasements suitable for monolith-supported 1 (left) and 2 (right).
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Scheme 3. Synthesis of monolithic discs and an immobilized version of 2.
Conclusion
spectra were recorded on a Bruker FT-IR. GC-MS measure-
ments were carried out on a Shimadzu GCMS QP5050, using
a SPB-5 fused silica column (30 mꢂ0.25 mm, 25 mm film thick-
ness) and He as carrier gas. Enantiomeric excess (ee) was de-
termined via GC on a Shimadzu GCMS-QP 5050 equipped
We have developed a synthetic approach that allows the
immobilization of both ruthenium-based Grubbs and
molybdenum-based, chiral Schrock catalysts on mono-
lithic discs. The supported versions of these catalysts
are readily accessible and can, due to their disc-like na-
ture, be used in combinatorial chemistry, parallel syn-
thesis and high throughput screening (HTS). Thus, the
placement of these discs in compartments that fit com-
mercially available HTS machines is expected to allow
running the desired reactions in one single batch under
TM
with a Supelco Beta Dex 120 fused silica capillary column
(
30 mꢂ0.25 mmꢂ0.25mm film thickness) or via chiral
HPLC. The HPLC system was equipped with a Cyclobond I
2
000 (Astec, USA, 150 mmꢂ2.0 mm), separations were car-
ried out using the mobile phases indicated in Table 2. Separa-
tions were carried out at T¼08C; flow¼0.2 mL/min. The in-
jection volume was 1 mL, a UV detector (Linear Uvis 200,
2
54 nm) was used. Compounds were identified by their mass
defined conditions. The fact that the discs themselves si- spectra. Elemental analyses were carried out at the Institute
multaneously serve as support, reaction vessel and fil- of Physical Chemistry, University of Vienna. A Jobin Yvon
tration unit underlines the simplicity of this set-up. Fur- JY 38 plus was used for ICP-OES measurements, an MLS
1
200 mega for microwave experiments. Further instrumenta-
ther investigations on this issue including the develop-
ment of technically relevant devices are under way.
[51]
tion is described elsewhere. Gel permeation chromatogra-
phy (GPC) using UV/RI/LS detection was carried out on a Wa-
ters Styragel column (HR4E 7.8ꢂ300 mm) equipped with a
Styragel guard column (4.6ꢂ30 mm). A 717 plus autosampler,
a 2414 differential refractometer, a 484 UV detector (all Wa-
ters) and a Minidawn light scattering detector (Wyatt Technol-
Experimental Section
ogies, USA, l¼690 nm) was used for measurements in CHCl .
3
General Remarks
A dn/dc of 0.465 mL/g was used for poly(DEDPM). Samples
were filtered through 0.2 mm Teflon filters (Millipore) in order
to remove particles. GPC columns were calibrated vs. polystyr-
ene standards [Polymer Standards Service (PSS), molecular
NMR data were obtained at 300 MHz in the indicated solvent
at 258C on a Bruker Spectrospin 300 and are listed in parts per
million downfield from tetramethylsilane. Spectra are report-
ed in reference to CDCl (7.24 and 77.0 ppm for proton and car-
bon, respectively). Coupling constants are listed in Hertz. IR
6
weights 580 to 1.57ꢂ10 g/mol]. Syntheses and polymeriza-
3
tions were performed under an argon atmosphere by standard
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Schlenk techniques or in an N -mediated dry-box (Braun, Ger-
tions (SPE, ICT, Isolute, Austria) were used as encasements for
these pieces. Ru loading: 6.6 mmol Ru/g monolith correspond-
ing to 5.5 mg catalyst/g monolith (0.55 wt %).
2
many) unless stated otherwise. Reagent grade diethyl ether,
pentane, tetrahydrofuran (THF) and toluene were distilled
from sodium benzophenone ketyl under argon. Reagent grade
CH Cl and 1,2-dichloroethane were distilled from calcium hy-
2
2
dride under argon. Other solvents and reagents were used
as purchased. Deionized water was used throughout.
RuCl (PCy ) (CHPh) was purchased from Fluka. endo-Nor-
RCM/Ring-Opening Cross-Metathesis
A representative RCM procedure was as follows: The mono-
lithic membrane (0.23 g, 1.5 mmol catalyst) was treated with
2
3 2
[67]
[42]
born-2-ene-5-carboxylic chloride,
(NBE-CH O) SiCH ,
2 3 3
0
.76 g of a 10 wt % solution of diethyl diallylmalonate (DE-
(
R)-5,5’-bis-(norborn-5-ene-2-ylmethyleneoxymethyl)-3,3’-di-
[29]
DAM) in CH Cl . This volume was readily absorbed by the
tert-butyl-6,6’-dimethylbiphen-2,2’-diol,
lyldimethylsilyloxy)-hepta-1,6-diene, 2,4-dimethyl-3-(dime-
thylvinylsilyloxy)-penta-1,4-diene,
N-(4-phenylbut-1-en-4-yl)aniline,
phenylbut-1-en-4-yl)aniline,
1
2,6-dimethyl-4-(al-
2
2
[58]
monolith. Other monolithic discs were treated in a similar
way using the monomers indicated in Table 1. The reaction ves-
sels were sealed, removed from the glove box and heated to
[
68–70]
N-(isobut-1-en-3-yl)-
[
55]
N-(allyl)-N-(2-methyl-4-
[
55]
3-allyloxy-3-phenylisobut-
458C for 2.8 h. Finally, reaction mixtures were eluted with
1
[65]
[29,68–70]
-ene,
3-allyloxy-2,4-dimethylpenta-1,4-diene,
CH
2
Cl
. Yields were determined by GC-MS and H NMR (us-
2
ing CDCl as solvent), respectively. In order to determine the
RuCl (PCy )(NHC)(CHPh) [NHC¼1-mesityl-3-(6-hydroxy-
3
2
3
[22]
total loss of ruthenium, the washings of all RCM investigations
were combined, digested in aqua regia by a microwave unit and
the ruthenium content was acquired by ICP-OES. A rutheni-
um loss <3% was determined.
hexyl)imidazl-2-inylidene],
and Mo[N-2,6-(i-Pr) -C H ]-
2 6 3
[71]
(
CHCMe Ph)(OSO CF ) .DME were prepared according
2
2
3 2
to literature procedures and checked for purity by means of
NMR.
Synthesis of Monolith-Supported Catalyst 2
RuCl (PCy )(1-mesityl-3-(6-acetoxyhexyl)imidazol-2-
inylidene) (CHPh)
2
3
Synthesis of monoliths was carried out according to published
[39–46]
procedures.
The following amounts were used: 2-propa-
Compound 1 (20 mg, 24 mmol) was dissolved in absolute
CH Cl . Tricyclohexylphosphine (6.5 mg, 24 mmol) and acetyl
nol (2.9 mL), (NBE-CH O) SiMe (1.000 g, 2.426 mmol),
2
3
2
2
NBE (1.000 g, 10.621 mmol), toluene (0.8 mL) and
RuCl (PCy ) (CHPh) (0.020 g, 0.024 mmol). PEEK column
chloride (75 mg, 950 mmol) were added and the reaction mix-
ture was stirred at 208C for 1.5 h. The solvent was removed un-
der vacuum and the residue was extracted with pentane. Crys-
2
3 2
dimensions (70ꢂ4.6 mm i.d., V ¼ 1.2 mL). After synthesis,
the monolith was flushed with CH Cl and filled with a solution
2
2
1
tallization at ꢀ378C yielded 5 mg of the product. H NMR
of
5,5’-bis(bicyclo[2.2.1]hept-5-ene-2ylmethoxymethyl)-
(
CDCl ): d¼19.23 (Ru¼CH), 7.51 (m, 1H), 7.33 (m, 2H),
3
3
0
,3’-di-tert-butyl-6,6’-dimethylbiphenyl-2,2’-diol
.100 mmol) and NBE (0.020 g, 0.212 mmol) in 0.5 mL of
(0.060 g,
7
1
2
.18 (m, 1H), 7.09 (t, 2H, J¼7.3 Hz), 6.95 (b, 2H), 6.79 (m,
H), 4.69 (t, 2H, J¼6.5 Hz), 4.06 (m, 2H, CH COOCH ),
3
2
CH Cl . The column was sealed and stored at 508C overnight.
2
2
.6–1.0 (m, 55H); MS (FAB): m/z calcd. for
The next day, the monolith was flushed for 30 min with diethyl
ether and further 30 min with ethyl vinyl ether in diethyl ether
þ
C H Cl N O PRu: 871.34; found: 870.89 [MþH ], 835.26
4
5
68
2
2
2
þ
[
MþH – HCl ].
(
10 vol % EVE, 0.2 mL/min). The monolith was dried under
vacuum. Potassium bis(trimethylsilyl)amide [KN(SiMe ) ]
3
2
(
0.200 g, 1.003 mmol) dissolved in a 1:1 mixture of diethyl
ether and THF was introduced into the monolith and kept at
room temperature overnight. Then, the monolith was flushed
thoroughly with diethyl ether. Mo[N-2,6-(i-Pr) -C H ]-
Synthesis of Monolith-Supported Catalyst 1
Synthesis of monoliths was carried out according to published
2
6
3
[39–46]
procedures.
The following amounts were used: norborn-2-
(CHCMe Ph)(OTf) (DME) (0.238 g, 0.301 mmol) dissolved
2 2
ene (NBE, 1.6 g, 17 mmol), (NBE-CH O) SiCH (1.54 mL,
in 4 mL of diethyl ether was injected over a period of 2 h. Final-
ly, the monolith was flushed with diethyl ether until the wash-
ings run through colorless and dried under vacuum. The mon-
olith was removed from the PEEK column. The dry monolith
was cut into pieces of about 1 cm in height. Each piece was
placed inside a syringe. The average molybdenum content
was 0.094 mmol/g, corresponding to a catalyst loading of 7
wt %.
2
3
3
1.6 g, 3.74 mmol), 2-propanol (4.8 mL), toluene (1.1 mL),
RuCl (PCy ) (CHPh) (32 mg). Column dimensions: 60ꢂ
2
3 2
1
2 mm i.d., V ¼ 7 mL. After monolith synthesis, the monolith
was washed with dry CH Cl . Norborn-5-ene-2-carboxylic
2
2
chloride (0.225 mL) was dissolved in 6 mL of dry CH Cl and
2
2
the solution was passed over the column. Graft-polymerization
was carried out at 458C for 15 h. The column was washed with a
4
0 vol % solution of ethyl vinyl ether in dry CH Cl followed by
2 2
dry CH Cl . A solution of 1 (20 mg, 24 mmol) and tricyclohex-
2
2
ylphosphine (14 mg, 48 mmol) in 5 mL of dry CH Cl was pre-
2
2
General Procedure for RCM of (Pro-) Chiral
Monomers
pared and 4 mL of this solution were introduced to the column.
The reaction was allowed to proceed for 1.5 h at 258C. After-
wards, the column was washed with dry CH Cl until the wash-
A solution of the corresponding monomer in CH Cl was add-
2
2
2
2
ings were colorless. Then the monolith was dried under vacuum
and brought into a glove box. The monolith was removed from
the SPE column and chopped into pieces of 200–250 mg (ap-
proximately 0.5 cm in height). Syringes for solid-phase extrac-
ed. The soaked monolith was kept at room temperature for 2 h.
Then, the monolith was flushed with pure CH Cl and the com-
bined washings were measured by GC-MS. In order to deter-
mine the total loss of molybdenum, the washings of all RCM
2
2
490
ꢂ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2005, 347, 484–492

DEDICATED CLUSTER
FULL PAPERS
Monolithic Disk-Supported Metathesis Catalysts
investigations were combined, digested in aqua regia by a mi-
crowave unit and the molybdenum content was acquired by
ICP-OES. A molybdenum loss <2% was determined.
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6] C. W. Bielawski, R. H. Grubbs, Angew. Chem. 2000, 112,
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3
Determination of the Metal Content
[
8] R. H. Grubbs, in: Handbook of Metathesis, Vol. 1–3, Wi-
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9] R. H. Grubbs, S. J. Miller, G. C. Fu, Acc. Chem. Res.
For the determination of catalyst loading, the monolithic sup-
ports (60.5 mg) were dried, mortared, placed inside high-pres-
sure teflon tubes and dissolved in aqua regia (3 mL). For the
determination of metal leaching, the combined effluents
were dried, the residue was placed inside high-pressure teflon
tubes and then aqua regia (3 mL) was added. Leaching was car-
ried out under microwave conditions (250, 600 and 450 W puls-
es; t¼32 min). After cooling to room temperature, the mixture
was filtered and water was added up to a weight of 10.00 g.
Quantification of the corresponding metal ion was accomplish-
ed by ICP-OES (ion line for Mo l¼202.030 nm; background
l ¼202.015 and l ¼202.045 nm, respectively; ion line for Ru
[
1
995, 28, 446.
[
10] A. Fꢀrstner, Angew. Chem. 2000, 112, 3140; Angew.
Chem. Int. Ed. 2000, 39, 3012–3043.
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[12] M. Schuster, S. Blechert, Angew. Chem. 1997, 109, 2124;
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[
1
2
[14] O. Fujimura, R. H. Grubbs, J. Org. Chem. 1998, 63, 824.
15] J. J. Van Veldhuizen, D. G. Gillingham, S. B. Garber, O.
l¼240.272 nm, background l ¼240.287 and l ¼240.257 nm,
1
2
[
respectively). Standardization was carried out using 0.0, 5.0,
and 10.0 ppm standards of the corresponding metal ion.
Kataoka, A. H. Hoveyda, J. Am. Chem. Soc. 2003, 125,
1
2502.
[
16] D. G. Gillingham, O. Kataoka, S. B. Garber, A. H. Hov-
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Polymerization of Diethyl Dipropargylmalonate
[
17] J. S. Kingsbury, A. H. Hoveyda, in: Polymeric Materials
in Organic Synthesis and Catalysis, (Ed.: M. R. Buchme-
iser), Wiley-VCH, Weinheim, 2003, p. 467.
(
DEDPM) with 1
Inside a glove-box, DEDPM (50 mg, 2112 mmol) was dissolved
in CH Cl (0.5 mL) and treated with a solution of 1 (1.0 mg,
[18] M. Mayr, B. Mayr, M. R. Buchmeiser, Designed Mono-
mers and Polymers 2002, 5, 325.
2
2
1
.2 mmol) in CH Cl (0.5 mL). Reactions were run at room
2 2
temperature and 408C, respectively, for 3 h. During this time,
the solution changed its color to dark violet. The reaction mix-
ture was concentrated to 0.5 mL and added to 50 mL of pen-
tane under stirring. Aviolet precipitate formed. It was collect-
ed by means of centrifugation, the supernatant solution was
decanted off, and the residue was washed with pentane (2ꢂ
[19] M. Mayr, B. Mayr, M. R. Buchmeiser, in: Studies in Sur-
face Science and Catalysis: Scientific Bases for the Prepa-
ration of Heterogeneous Catalysts, Vol. 143, (Eds.: E.
Gaigneaux, D. E. DeVos, P. Grange, P. A. Jacobs, J. A.
Martens, P. Ruiz, G. Poncelet), Elsvier, Amsterdam,
2
002, p. 305.
4
mL) and dried under vacuum. The UV spectrum in CHCl
3
[
[
20] M. R. Buchmeiser, New. J. Chem. 2004, 28, 549.
21] A. H. Hoveyda, D. G. Gillingham, J. J. Van Veldhuizen,
O. Kataoka, S. B. Garber, J. S. Kingsbury, J. P. A. Harrity,
Org. Biomol. Chem. 2004, 2, 8.
showed a maximum at l¼535 nm, respectively, with an addi-
tional shoulder at 575 nm. GPC (room temperature polymeri-
zation): M ¼15,500; M ¼11,100, PDI¼1.4; GPC (polymeri-
w
n
zation at 408C): M ¼16,400; M ¼11,700, PDI¼1.4 (values
w
n
13
[22] S. Prꢀhs, C. W. Lehmann, A. Fꢀrstner, Organometallics
004, 23, 280.
from RI). The C NMR spectrum was in accordance with
one of poly(DEDPM) consisting at least 95% of 5-membered
2
[47,72–76]
[23] S. C. Schꢀrer, S. Gessler, N. Buschmann, S. Blechert, An-
gew. Chem. 2000, 112, 4062; Angew. Chem. Int. Ed. 2000,
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3
9, 3898–3901.
[
[
24] S. Randl, N. Buschmann, S. J. Connon, S. Blechert, Syn-
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25] S. J. Connon, A. M. Dunne, S. Blechert, Angew. Chem.
Acknowledgements
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002, 114, 3989; Angew. Chem. Int. Ed. 2002, 41, 3835–
Financial support provided by the Austrian Science Fund (FWF
Vienna, project Y-158) is gratefully acknowledged.
3838.
[
[
[
26] S. J. Connon, S. Blechert, Bioorg. Med. Chem. Lett. 2002,
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