Olefin metathesis on a TLC Plate as a Tool for a High-Throughput Screening of Catalyst-Substrate Sets

Article abstract of DOI:10.1002/adsc.201100863

A methodology for screening either various catalysts for a given metathesis reaction, i.e., ring opening-ring closing alkene metathesis (RO-RCM) and cross-metathesis (CM), or various substrates for a given pre-catalyst on a thin layer chromatography (TLC) plate has been developed. As the substrates elute with the solvent, this TLC-based system acts as a heterogeneous catalyst bed ("TLC reactor"). Selected promising catalyst candidates were screened on a TLC plate and their initial catalytic potential as observed in the TLC test was later fully confirmed in a classical heterogeneous reaction set-up using standard commercially available silica (D11-10). Reacting polyfunctional, natural product-like substrates in our TLC reactor allows the simultaneous screening of various substrates and the convenient micro-scale preparation and isolation of potentially biologically active products. Copyright

Full text of DOI:10.1002/adsc.201100863

FULL PAPERS
DOI: 10.1002/adsc.201100863
Olefin Metathesis on a TLC Plate as a Tool for a High-Through-
put Screening of Catalyst-Substrate Sets
a
a
b
b
Josꢀ Cabrera, Robin Padilla, Richard Dehn, Stephan Deuerlein,
c,d
c,e
b
a,b,
Łukasz Gułajski, Ewa Chomiszczak, J. Henrique Teles, Michael Limbach, *
and Karol Grela *
CaRLa – Catalysis Research Laboratory, Im Neuenheimer Feld 584, 69120 Heidelberg, Germany
BASF SE, Basic Chemicals Research, Carl-Bosch-Strasse 38, 67056 Ludwigshafen, Germany
c,
a
b
Fax : (+49)-621-60-6648957; phone: (+49)-621-60-48957; e-mail: michael.limbach@basf.com
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01–224 Warsaw, Poland
c
Fax : (+48)-22-632-6681; phone: (+48)-22-343-2117; e-mail: klgrela@gmail.com
Apeiron Synthesis Sp. z o.o., Kleci n´ ska 125, 54–413 Wrocław, Poland
Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00–664 Warsaw, Poland
d
e
Received: November 3, 2011; Revised: January 27, 2012; Published online: April 13, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100863.
Abstract: A methodology for screening either vari- fully confirmed in a classical heterogeneous reaction
ous catalysts for a given metathesis reaction, i.e., set-up using standard commercially available silica
ring opening-ring closing alkene metathesis (RO- (D11-10). Reacting polyfunctional, natural product-
RCM) and cross-metathesis (CM), or various sub- like substrates in our TLC reactor allows the simulta-
strates for a given pre-catalyst on a thin layer chro- neous screening of various substrates and the con-
matography (TLC) plate has been developed. As the venient micro-scale preparation and isolation of po-
substrates elute with the solvent, this TLC-based tentially biologically active products.
system acts as a heterogeneous catalyst bed (“TLC
reactor”). Selected promising catalyst candidates
were screened on a TLC plate and their initial cata- Keywords: biphasic catalysis; homogeneous catalysis;
lytic potential as observed in the TLC test was later metathesis; ruthenium; thin layer chromatography
Introduction
anionic ligand can have a tremendously beneficial
effect on the stability of the complexes. Nevertheless,
A plethora of concepts has been developed to immo- the synthesis of such hybrids is time and labour inten-
bilize well-defined organometallic complexes on sur- sive and requires correspondingly modified ligands or
faces with the hope to combine the advantages of ho- surfaces.
[
1]
mogeneous and heterogeneous catalysis, i.e., to
On the other hand, it is more economical to physi-
obtain materials with the activity of a homogeneous sorb an unmodified, commercially available homoge-
catalyst and the usability of a heterogeneous one. neous complex to an unmodified, inorganic material.
[
7]
[8]
Such hybrid catalysts have most systematically been Sels et al. and later others have shown that for ob-
studied in the field of olefin metathesis and the devel- taining a truly heterogeneous metathesis catalyst,
opment has been facilitated by the robustness of pre- a weak physical interaction between a neutral com-
complexes based on the late transition metal rutheni- plex and the inorganic surface is sufficient if the reac-
[2]
um.
tion conditions are chosen appropriately. In order not
The homogeneous complex has either been at- to leach off complex, this methodology is limited to
tached to a heterogeneous organic or inorganic sur- apolar solvents and substrates but as there is no need
face by covalent organic tethers bound to a li- to introduce tagged ligands into the complex, the ad-
[
2b,3,4,5]
gand,
or the unmodified inorganic surface coor- sorptive approach of Sels et al. is elegant as well as in-
[6]
dinates directly to the metal as a huge ligand. This dustrially highly attractive.
covalent anchoring to a silica surface acting as an
Adv. Synth. Catal. 2012, 354, 1043 – 1051
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1043

Josꢀ Cabrera et al.
FULL PAPERS
Figure 1. Catalysts 1–34 employed in this study. Abbreviations: Ind: 3-phenylindenylidene, Ad: adamantyl, i-Bu: isobutyl, i-
Pr: isopropyl, Mes: mesityl, Cy: cyclohexyl, SIMes: N,N’-bis[2,4,6-(trimethyl)phenyl]imidazolidin-2-ylidene, IMes: N,N’-bis-
[2,4,6-(trimethyl)phenyl]imidazol-2-ylidene.
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
As there is an abundance of known ruthenium- pensive and fast method to evaluate in a combinatorial
based pre-catalysts for the metathesis reaction, we way the activity of organometallic complexes on a sup-
[
9,10]
have been interested in developing a methodology to port.
screen the stability and activity of structurally diverse
ruthenium carbenes for a given substrate on a silica
support without preparing each individual hybrid ma- Results and Discussion
terial.
Our main target has been the systematic evaluation Cross-Metathesis (CM) and Ring Opening–Ring
of the activity and stability of 34 structurally diverse Closing Metathesis (RO-RCM) on a TLC Plate
pre-catalysts for the metathesis reaction (Figure 1) in
the context of a biphasic solid/liquid system in order As the target reaction for the TLC test we chose the
[
11]
to identify a homogeneous complex that is sufficiently self-CM of methyl 9-decenoate and the RO-RCM
[
12]
active and stable on the silica support for further de- of cis-cyclooctene.
While the first transformation
velopment as a heterogeneous metathesis catalyst. To yields dimethyl 9-octadecenoate, an interesting prod-
achieve this goal, we used thin layer chromatography, uct for specialty chemical applications (Scheme 1),
which has already previously been used as an inex- the latter reaction is one of the shortest routes to
1044
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1043 – 1051

Olefin Metathesis on a TLC Plate as a Tool for a High-Throughput Screening
[
15]
[16]
[17] [18]
(
e.g., 2, 3, 4,
tain a P-ligand.
Amongst the pre-complexes not containing a P-
5
). Note that all of them con-
[19]
ligand, two were bis-NHC complexes (i.e., 11 and
[
20]
rd
[21]
1
2
), one
3
generation complex (13
) and
a number of pre-catalysts containing either an N-Ru
[
14a]
[22]
(
(
7–10,
14, 15), a S-Ru (27 ) or an O-Ru chelate
Grubbs–Hoveyda-type pre-catalysts; 16–26, 28–34).
Scheme 1. Targeted reactions on a TLC plate: CM of methyl
-decenoate and RO-RCM of cis-cyclooctene.
On commercially available TLC plates (Macherey
9
& Nagel), solutions of complexes 1–34 in CH Cl2
2
were spotted. Immediately after solvent evaporation,
methyl 9-decenoate was spotted over the now physi-
macrocyclic skeletons that serve as precious starting sorbed pre-catalysts and the plate was allowed to
materials for certain fine-chemicals, e.g., macrocyclic stand for 24 h of reaction time. The chromatogram
ketones.
was then developed in AcOEt/hexane 1:7 (v/v), and
For these two target reactions, we screened a library stained with phosphomolybdic acid (Figure 2, a). The
of 34 pre-catalysts (Figure 1). Amongst those com- activity of the complexes was ascertained by the pres-
st
plexes, two were representatives of the 1 generation ence of the clearly separated dimethyl octadecenoate
[13]
[14a]
nd
(
1,
6
) and four were 2 generation complexes spot, one of the self-CM products.
Figure 2. Self-CM of methyl 9-decenoate with complexes 1–34. a) “Immediate reaction” on TLC plate (spot of catalyst, then
immediately spot of methyl 9-decenoate and after 24 h, development of the plate in AcOEt/hexane 1:7 (v/v). b) “Delayed
reaction” on TLC plate (spot of catalyst and after 6 h, spot of methyl 9-decenoate, followed by 18 h reaction time and then
plate development in AcOEt/hexane 1:7 [v/v]). For catalyst structures see Figure 1.
Adv. Synth. Catal. 2012, 354, 1043 – 1051
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1045

Josꢀ Cabrera et al.
FULL PAPERS
Figure 3. RO-RCM of cis-cyclooctene with complexes 1–34, using the regular TLC procedure (spot the complexes, then the
cyclooctene and develop the TLC right away in hexane).
[
24]
[32]
[33]
Remarkably, apart from the complexes with the 29 and 30 showed significant activity. Again, 27
Grubbs–Hoveyda motif (16–26, 28–30, 32–34), only and 31 remained latent at room temperature.
complexes 4 and 11–13 were active on the TLC plate.
[
14]
Neither the N-chelate complexes 6–10,
14 and 15
st
nd
nor the 1 or 2 generation complexes, i.e., pre-cata- RO-RCM of cis-Cyclooctene on Silica
lysts containing P-ligands, gave a product spot at
[
23]
room temperature. The latency of pre-catalyst 27
To determine if the screening results obtained on
[
24]
and the poor solubility of 31 precluded the reaction a TLC plate were reliable, we more closely examined
yielding dimethyl octadecenoate. the effect of the silica surface in the RO-RCM of cis-
To probe the stability of the complexes on the silica cyclooctene. Thus, a set of hybrid materials consisting
nd
rd
plate, a solution of the pre-catalysts in CH Cl was of untagged 2 and 3 generation (3, 13) and
2
2
spotted on the TLC plate and only after 6 h of poten- Grubbs–Hoveyda-based (16, 17, 23, 24 and 29) pre-
[34]
tial “reaction time” with the silica surface, was methyl catalysts with commercially available silica D11-10
-decenoate added. The chromatogram was then de- as solid support was prepared. By impregnation of
veloped after 18 h. In this “delayed reaction” scenar- D11-10 with a solution of the appropriate complex in
9
[
25]
[26]
io, pre-complexes 4, 11–13, 28, 32, 33 and 34 all CH Cl and subsequent removal of volatiles, it was
2
2
substantially lost activity (Figure 2, b). This situation possible to load between 73 and 100% of the initial
might be a result of complex degradation on the silica ruthenium amount onto D11-10 to give red-brown
surface, especially of those catalysts containing P-li- (for 3) or greenish materials. These amounts corre-
[27]
gands.
Long-term stability on the TLC plate was spond to a Ru-loading of 0.18–0.25 wt%.
only observed for pre-catalysts with the Grubbs–Hov-
When these materials were used in the RO-RCM
[
28]
eyda II motif, e.g., Hoveydaꢂs paragon 16,
the of cis-cyclooctene (Scheme 2, Table 1) in hexane as
[29]
nitro-catalyst 17 or Zhannan catalyst 23, an obser- solvent (in which the Ru complexes should be poorly
[
7]
vation that supports previous studies.
soluble), high conversions were obtained. Unfortu-
[
7]
When the mentioned test protocol for pre-catalysts nately in the case of 3, a split test later showed the
1
–34 was applied to the RO-RCM of cis-cyclooctene reaction to be homogeneous due to desorption of im-
(
Figure 3), and the TLC was developed right away in
nd
hexane, the result was similar: Of the 2 and other
generation complexes only 4, 9, 11 and 13 showed ac-
tivity as indicated by a spot for the cyclodimer 1,8-cy-
clohexadecadiene (amongst a multitude of spots for
the other oligomeric multiples of cyclooctene). Of the
Scheme 2. Evaluation of heterogenized, untagged pre-cata-
complexes with the Grubbs–Hoveyda II motif, only lysts on silica in the RO-RCM of cis-cyclooctene. For de-
[30]
[30]
[31]
16, 17, 24,
25
and the ionic pre-catalysts 28,
tails, see Table 1.
1046
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1043 – 1051

Olefin Metathesis on a TLC Plate as a Tool for a High-Throughput Screening
Table 1. Evaluation of heterogenized, untagged pre-catalysts Simultaneous Olefin Metathesis and Purification on
on silica.
a TLC Plate
Catalyst Conversion
Split test
[Ru]
[wt%]
Loading
[%]
[a]
Having shown that testing the activity and longevity
of metathesis catalysts on a TLC-plate is an efficient
and reliable technique, we sought to apply our newly
developed methodology to reactions involving poly-
functional, natural product-like substrates. After
screening a large number of catalysts on a TLC plate
in order to identify an optimal set for a given reac-
tion, we applied this concept to allow the simultane-
ous screening of various substrates with one given cat-
alyst, e.g., with tagged ruthenium complex 29. The
usage of such a TLC reactor would allow for the con-
venient preparation and isolation of larger sets of po-
[%]
3
1
1
1
2
2
2
97
25
59
44
43
66
60
homogeneous 0.18
heterogeneous 0.21
heterogeneous 0.18
heterogeneous 0.16
heterogeneous 0.22
heterogeneous 0.25
heterogeneous 0.20
82
100
82
3
6
7
3
4
9
73
100
100
92
[
a]
Conversion after 0.5 h.
mobilized complex into solution. The same reaction tentially biologically active products in a short time.
with 13 was confirmed to be heterogeneous but the In this set-up, the catalyst is immobilized on an ana-
activity was low (25% conversion) in spite of a slightly lytical or preparative TLC plate. The substrates mi-
higher ruthenium concentration in the material grate through the catalyst zone during the TLC plate
(
0.21 wt%, i.e., 100% of the initial amount). This out- development, where they undergo olefin metathesis
come is most likely due to deactivation, as seen in the (Figure 4). The unreacted substrate and the expected
TLC test. The Grubbs–Hoveyda II type complexes metathesis product (and by-products) then migrate to
1
6, 17, 23, 24 and 29 all worked heterogeneously and the top of the TLC plate. At this point, they can be
73–100% of the initial complex was adsorbed, result- visualized, showing reaction conversion and selectivi-
ing in a final ruthenium concentration of 0.18– ty. When a preparative TLC plate is used, the prod-
.25 wt%. These results confirmed the validity of the ucts can be isolated from the plate by the standard
TLC-based screening results. protocols used in preparative TLC. This technique
0
Figure 4. Four simultaneous olefin metathesis and purification sequences made using catalyst 29 on a TLC plate (green
zone: immobilized catalyst 29).
Adv. Synth. Catal. 2012, 354, 1043 – 1051
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1047

Josꢀ Cabrera et al.
FULL PAPERS
Table 2. Selected products obtained by metathesis using 29 on with samples of products and substrates that were in-
a TLC plate.
dependently developed.
Using a similar technique, an Ru-impregnated
Entry Substrate
Product
Yield
preparative TLC plate, 6ꢃ20 cm (Merck, Kieselgel 60
F254, 1 mm) was prepared and the usefulness of this
TLC protocol was further examined by conducting
several preparative RCM and CM reactions with vari-
ous dienes and enynes, run at a 0.05-mmol scale. The
results of these experiments are summarized in
Table 2, entries 1–7. All model substrates reacted
smoothly to form various functionalized cyclic prod-
ucts, including polar ones (Table 2, entries 1–5 and 7).
The products were removed from the TLC using stan-
dard techniques used in preparative TLC, (removal of
silica layer with a spatula, extraction with an organic
solvent, filtration and concentration to dryness). Iso-
lated yields of pure products were usually good (97–
61%). The reactivity of 29 on the TLC plate in a self-
CM reaction (Table 2, entry 6) was tested and gave
the desired product with moderate yield (55%).
[
%]
1
2
97
91
3
61
4
5
95
94
Complex 29 turned out to be surprisingly stable on
the TLC plates and can be stored for five days with-
out loss of activity. In order to rigorously test the sta-
bility of catalyst 29, we first investigated whether such
ruthenium-impregnated TLC plates could be used
more than once, e.g., in the enyne metathesis of allyl
6
7
55
75
1,1-diphenyl-2-propynyl ether (A) and the RCM reac-
tion of N,N-diallyltosylamide (B), cf. Scheme 3. After
each reaction, the TLC plate was dried and the top
part of the plate was cut off to remove the product-
containing zone. The shortened TLC plate was then
stored for a day under air and used again. This proto-
col was repeated 5 times (cf. Table 3) using the same
TLC plate.
thus combines the olefin metathesis reaction with si-
multaneous product purification. As the catalyst re-
mains bound to the silica, another advantage of this
2D metathesis technique is that it circumvents the re-
moval of dark-coloured residues that often arise from
spent metathesis catalysts.
To execute our idea, we immobilized catalyst 29
5 mg) on a standard analytical TLC plate, 4ꢃ8 cm in
(
dimension (Merck, Kieselgel 60 F ). The catalyst Scheme 3. Consecutive enyne metathesis (A) and RCM (B)
254
was spotted over a rectangular area starting just by using 29 on a TLC plate. For details, see Table 3.
above the substrate line (R =0) and occupied ca. 20
f
area% of the plate (Figure 4). Next, the plate was
dried and four model substrates were lined up at the
baseline (spots I–IV).
Table 3. Consecutive enyne metathesis (A) and RCM (B) by
using 29 on a TLC plate.
The TLC plate was then developed using AcOEt
and n-hexane (1:2 or 1:5 [v/v]) as an eluent and prod-
uct spots were visualized by UV and by spraying an
anisaldehyde/sulfuric acid dye on to the plate. The re-
sults showed very good conversion in all cases
Cycle
1
2
3
4
5
[
a]
Conv. A (%)[
Conv. B (%)
95
75
75
79
65
49
55
–
40
–
a]
[a]
(
Figure 4). The identity of the products was proven by
Conversion was determined by GC analysis of the crude
reaction mixture.
comparing their R values and colours after dyeing
f
1048
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1043 – 1051

Olefin Metathesis on a TLC Plate as a Tool for a High-Throughput Screening
Although in the enyne metathesis the conversion Representative Procedure for the Heterogenization
decreased slowly over 5 cycles (from 95 to 40%) and of 16 on Silica
even faster for the RCM (from 75 to 49% in 3
The D11–10 silica (1.5 g, 1.5 mm strands) was weighed into
cycles), this result nonetheless shows the extraordina-
a flask (100 mL). Under argon, CH Cl (10 mL) was added
2
2
ry stability of 29 immobilized on silica.
and a solution of 16 (20.5 mg, 32.7 mmol) in CH Cl (10 mL)
2
2
was added. The suspension was shaken (200 rpm) overnight
at room temperature under argon. Volatiles were removed
in the vacuum at max. 408C to give a green material (ICP-
MS for Ru: 0.22% (theoertical), 0.18% (found).
Conclusions
In conclusion, we have shown that an experimentally
simple set-up using a TLC plate as a “reactor” can be
used to screen the optimal catalyst structure for
Tests with the Heterogenized Catalysts
a given substrate or to prepare a diverse set of even In a glove-box, the Ru-loaded silica (~500 mg) was suspend-
ed in a mixture of n-hexane (16 mL) and dodecane (1.01 g).
natural product-like compounds with a given catalyst.
Cyclooctene (148 mg, 1.30 mmol) was added at room tem-
For both cases it is crucial that the catalyst adsorbs
perature and the suspension was shaken at 200 rpm. Sam-
strongly on silica, which was found to be the case for
ples were taken after 30 min. The analytical samples were
catalysts with the Grubbs–Hoveyda motif, an observa-
quenched with ethyl vinyl ether to deactivate the catalyst.
tion also confirmed in conventional heterogeneous
catalytic tests. Our TLC-reactor is a convenient quali-
tative tool for the high-throughput screening of cata- RCM, Enyne and CM Metathesis on Preparative
lysts as well as for the micro-scale preparation of val- TLC Plate
uable products and is particularly suitable for applica-
Solutions of complex 29 (10 mg, 50 mmol) in CH Cl (2 mL)
were spotted on the TLC plate and then a solution of the
2
2
tion in the pharmaceutical and the fine chemical in-
dustry. However, to further explore the activity, selec-
tivity and stability of a given heterogenized catalyst in
starting material (20 mg, 25 mmol) in CH Cl (1 mL) was ap-
2
2
plied at the baseline to each spot. The TLC plate was devel-
a quantitative way, continuous-flow experiments are oped (AcOEt/hexane 1:2 or 1:5). After the development of
mandatory.
the TLC plate, the spot of product was scraped off and then
extracted with CH Cl . Purity and conversion was checked
2
2
1
by using H NMR and GC.
-Phenyl-3,6-dihydro-2H-pyran (Table 2, entry 1):
[
35]
2
Col-
Experimental Section
1
ourless oil. H NMR (400 MHz, CDCl ): d=2.21–2.44 (m,
3
2
5
H), 4.33–4.39 (m, 2H), 4.56 (dd, J=3.8, 10.0 Hz, 1H),
.77–5.85 (m, 1H), 5.88–5.97 (m, 1H), 7.26–7.43 (m, 5H).
The catalysts were either commercially available via Sigma-
Alrich/Materia (1, 2, 16), Strem (3, 4, 5, 10, 13, 14, 15, 23),
Omꢀga Cat System (18–22), Evonik (27), Apeiron Synthesis
1
-(2,5-Dihydrobenzo[b]oxepin-7-yl)ethanone
(Table 2,
3
1
entry 2): Colourless oil. H NMR (400 MHz, CDCl ): d=
(
28–33) or Umicore (24, 34) or were directly supplied by the
2
5
7
.56 (s, 3H), 3.52–3.56 (m, 2H), 4.60–4.66 (m, 2H), 5.49–
.56 (m, 1H), 5.86–5.95 (m, 1H), 7.09 (d, J=8.22 Hz, 1H),
.70–7.75 (m, 1H), 7.77–7.83 (m, 1H).
corresponding authors cited appropriately in the reference
section.
GC (column DB5 15 m; ID 0.32 mm; film thickness
2
-(2,5-Dihydropyrrole-1-carbonyl)-pyrrolidine-1-carboxyl-
À1
0
3
.25 mm; temperature program: 608C [5 min], 108Cmin to
008C, 3008C [15 min], 108Cmin
ic acid tert-butyl ester (Table 2, entry 3): Colourless oil.
À1
to 3208C, 3208C
1
H NMR (200 MHz, CDCl ): d=1.15–1.55 (m, 9H), 1.70–
3
[
18 min]): tR (cis-cyclooctene): 2.03 min, tR (C H ):
16 28
2
5
.25 (m, 4H), 3.30–3.65 (m, 2H), 4.00–4.60 (m, 5H), 5.65–
.90 (m, 2H).
16.58 min.
2
-(2,3,4-Trimethoxyphenyl)-3,6-dihydro-2H-pyran
1
RO-RCM and CM on a TLC Plate
(
Table 2, entry 4): Colourless oil. H NMR (400 MHz,
CDCl ): d=2.18–2.32 (m, 2H), 3.85 (s, 3H), 3.87 (s, 3H),
3
Solutions of the different Ru complexes in CH Cl were
2
2
3.90 (s, 3H), 4.27–4.41 (m, 2H), 4.81 (dd, J=10.0, 3.6 Hz,
2H), 5.76–5.83 (m, 1H), 5.89–5.96 (m, 1H), 6.70 (d, J=
8.7 Hz , 1H), 7.13 (d, J=8.7 Hz , 1H).
spotted on the TLC plate and then a solution of the starting
material in hexane was applied to each spot as soon as the
solvent had evaporated. The TLC plate was developed using
the appropriate eluent for each reaction (AcOEt/hexane 1:7
for CM and hexane for RO-RCM). After the development
of the TLC plate, the spots of starting material and prod-
uct(s) were stained with a solution of phosphomolybdic acid
in ethanol.
2
,2-Diphenyl-3-vinyl-2,5-dihydrofuran
(Table 2,
3
[
36]
1
entry 5): Colourless oil. H NMR (200 MHz, CDCl ): d=
4
.78–4.81 (m, 2H), 5.11 (dd, J=11.2, 0.6 Hz, 1H), 5.33 (dd,
J=17.6, 0.6 Hz, 1H), 6.16–6.22 (m, 1H), 6.22–6.30 (m, 1H),
.11–7.40 (m, 10H).
Dimethyl (2R*,9R*)-2,9-bis
methylprop-2-en-1-yl)-3-oxocyclopentyl]dec-5-enedioate
7
AHCTUNGTERNNUNG[ (1R*,2R*)-2-methyl-2-(2-
1
(
Table 2, entry 6): Colourless oil. H NMR (200 MHz,
CDCl ): d=0.95 (s, 6H), 1.55 (s, 6H), 1.30–2.00 (m, 7H),
3
2
4
.25–2.60 (m, 7H), 3.69 and 3.70 (s, 6H), 4.62 (br s, 2H),
.78–4.86 (m, 2H), 5.30–5.41 (m, 2H).
Adv. Synth. Catal. 2012, 354, 1043 – 1051
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1049

Josꢀ Cabrera et al.
FULL PAPERS
[
37]
N-Tosyl-2,5-dihydropyrrole (Table 2, entry 7):
White
[6] a) B. Marciniec, S. Rogalski, M. J. Potrzebowski, C. Pie-
traszuk, ChemCatChem 2011, 3, 904–910; b) S. Rogal-
ski, C. Pietraszuk, B. Marciniec, J. Organomet. Chem.
2009, 694, 3918–3922.
1
solid. H NMR (200 MHz, CDCl ): d=2.41 (s, 3H), 4.10 (d,
J=4.5 Hz, 4H), 5.64 (d, J=4.5 Hz, 2H), 7.31 (d, J=8.3 Hz,
3
2
H), 7.71 (d, J=8.3 Hz, 2H).
[
7] B. van Berlo, K. Houthoofd, B. F. Sels, P. A. Jacobs,
Adv. Synth. Catal. 2008, 350, 1949–1953.
ˇ
[
8] a) H. Balcar, T. Shinde, N. Zilkovꢅ, Z. Bastl, Beilstein J.
Acknowledgements
Org. Chem. 2011, 7, 22–28; b) R. M. Martꢆn-Aranda, J.
Cejka, Top. Catal. 2010, 53, 141–153; c) D. Bek, N.
ˇ
J.C., R.P. and M.L. work at CaRLa of Heidelberg University,
being co-financed by University of Heidelberg, the State of
Baden-Wꢀrttemberg and BASF SE. Support of these institu-
tions is greatly acknowledged. This work was supported by
grant number NN204404940, which was provided by the
Polish Ministry of Science and Higher Education. Special
thanks are given to Mr. Jan Klain and Ms. Annette Baumann
for some preliminary work and to Dr. Michał Michalak for
donation of model substrates.
ˇ
ˇ
ˇ
Zilkovꢅ, J. Dꢀdecek, J. Sedlꢅcek, H. Balcar, Top. Catal.
010, 53, 200–209; d) H. Balcar, D. Bek, J. Sedlꢅ cˇ ek, J.
Dꢀde cˇ ek, Z. Bastl, M. Lama cˇ , J. Mol. Catal. A: Chem.
010, 332, 19–24; e) H. Staub, R. Guillet-Nicolas, N.
2
2
Even, L. Kayser, F. Kleitz, F.-G. Fontaine, Chem. Eur.
J. 2011, 17, 4254–4265.
[
9] O. Lavastre, R. Touzani, S. Garbacia, Adv. Synth. Catal.
2
003, 345, 974–977.
[
[
[
10] J.-L. Raymond, T. Koch, J. Schrçer, E. Tierney, Proc.
Natl. Acad. Sci. USA 1996, 93, 4251–4256.
11] R. Baker, M. J. Crimmin, Tetrahedron Lett. 1977, 18,
441–442.
References
12] a) S. Kavitake, M. K. Samantaray, R. Dehn, S. Deuer-
lein, M. Limbach, J. A. Schachner, E. Jeanneau, C. Co-
pꢀret, C. Thieuleux, Dalton Trans. 2011, 40, 12443–
12446; b) W. J. Zuercher, M. Hashimoto, R. H. Grubbs,
J. Am. Chem. Soc. 1996, 118, 6634–6640; c) J. P. A.
Harrity, D. S. La, D. R. Cefalo, M. S. Visser, A. H. Hov-
eyda, J. Am. Chem. Soc. 1998, 120, 2343–2351; d) C.
Stapper, S. Blechert, J. Org. Chem. 2002, 67, 6456–
6460; e) K. L. Jackson, J. A. Henderson, H. Motoyoshi,
A. J. Phillips, Angew. Chem. 2009, 121, 2382–2386;
Angew. Chem. Int. Ed. 2009, 48, 2346–2350; f) Y. Chau-
vin, D. Commereuc, G. Zaborowski, Makromol. Chem.
[
1] Recent reviews: a) M. R. Maurya, J. C. Pessoa, J. Orga-
nomet. Chem. 2010, 696, 244–254; b) A. C. Marr, P. C.
Marr, Dalton Trans. 2011, 40, 20–26; c) A. Corma, H.
Garcia, Top. Catal. 2008, 48, 8–31; d) R. Duque, E.
ꢄchsner, H. Clavier, F. Caijo, S. P. Nolan, M. Mauduit,
D. J. Cole-Hamilton, Green Chem. 2011, 13, 1187–1195.
2] a) V. Riollet, E. A. Quadrelli, C. Copꢀret, J.-M. Basset,
R. A. Andersen, K. Kçhler, R.-M. Bçttcher, E. Herdt-
weck, Chem. Eur. J. 2005, 11, 7358–7365; b) F. Blanc,
C. Copꢀret, J. Thivolle-Cazat, J.-M. Basset, A. Lesage,
L. Emsley, A. Sinha, R. R. Schrock, Angew. Chem.
[
2
1
006, 118, 1238–1242; Angew. Chem. Int. Ed. 2006, 45,
216–1220; c) B. Rhers, A. Salameh, A. Baudouin,
1
978, 179, 1285–1290; g) H. Hçcker, W. Reimann, K.
Riebel, K. Szentivanyi, Z. Makromol. Chem. 1976, 177,
E. A. Quadrelli, M. Taoufik, C. Copꢀret, F. Lefebvre,
J.-M. Basset, X. Solans-Monfort, O. Eisenstein, W. W.
Lukens, L. P. H. Lopez, A. Sinha, R. R. Schrock, Orga-
nometallics 2006, 25, 3554–3557.
1
707–1715; h) H. Hçcker, J. Mol. Catal. 1991, 65, 95–
9
9; i) J.-P. Arlie, Y. Chauvin, D. Commereuc, J.-P. Souff-
let, Makromol. Chem. 1974, 175, 861–872; j) G.
Pampus, G. Lehnert, Makromol. Chem. 1974, 175,
[
[
3] a) S.-W. Chen, J. H. Kim, S.-g. Lee, Org. Biomol. Chem.
2
605–2616.
13] T. R. Belderrain, R. H. Grubbs, Organometallics 1997,
6, 4001–4003.
2
008, 6, 2676–2678; b) T. S. Halbach, S. Mix, D. Fischer,
[
[
S. Maechling, J. O. Krause, C. Sievers, S. Blechert, O.
1
Nuyken, M. R. Buchmeiser, J. Org. Chem. 2005, 70,
14] a) J. A. Schachner, J. Cabrera, R. Padilla, C. Fischer,
P. A. van der Schaaf, R. Pretot, F. Rominger, M. Lim-
bach, ACS Catalysis 2011, 1, 872–876; b) D. M. Hudson,
E. J. Valente, J. Schachner, M. Limbach, K. Mꢇller, H.-
J. Schanz, ChemCatChem 2011, 3, 297–301.
4
687–4694. For a review, cf. c) M. R. Buchmeiser,
Chem. Rev. 2009, 109, 303–321.
4] Grubbs systems: a) X. Elias, R. Pleixats, M. W. C. Man,
J. J. E. Moreau, Adv. Synth. Catal. 2006, 348, 751–762;
b) X. Elias, R. Pleixats, M. Wong Chi Man, Tetrahedron
[
[
15] M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett.
2
008, 64, 6770–6781; c) K. Melis, D. De Vos, P. Jacobs,
1
999, 1, 953–956.
F. Verpoort, J. Mol. Catal. A: Chem. 2001, 169, 47–56;
d) L. Li, J.-l. Shi, Adv. Synth. Catal. 2005, 347, 1745–
16] B. R. Galan, M. Pitak, M. Gembicky, J. B. Keister, S. T.
Diver, J. Am. Chem. Soc. 2009, 131, 6822–6832.
17] T. Opstal, F. Verpoort, New J. Chem. 2003, 27, 257–262.
18] L. Jafarpour, H.-J. Schanz, E. D. Stevens, S. P. Nolan,
Organometallics 1999, 18, 5416–5419.
19] L. H. Peeck, H. Plenio, Organometallics 2010, 29, 2761–
2766.
20] V. Sashuk, L. H. Peeck, H. Plenio, Chem. Eur. J. 2010,
1
749; e) J. O. Krause, S. Lubbad, O. Nuyken, M. R.
[
[
Buchmeiser, Adv. Synth. Catal. 2003, 345, 996–1004;
f) S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hov-
eyda, J. Am. Chem. Soc. 2000, 122, 8168–8179; g) J.
Lim, S. Seong Lee, J. Y. Ying, Chem. Commun. 2008,
[
ˇ
312–4314; Schrock systems: h) H. Balcar, N. Zilkovꢅ,
4
[
J. Zednꢆk, J. Mol. Catal. A: Chem. 2005, 232, 53–58;
review: i) C. Copꢀret, J.-M. Basset, Adv. Synth. Catal.
1
6, 3983–3993.
2
007, 349, 78–92.
[21] S. Monsaert, R. Drozdzak, V. Dragutan, I. Dragutan, F.
ˇ
Verpoort, Eur. J. Inorg. Chem. 2008, 3, 432–440.
[
5] D. Bek, H. Balcar, N. Zilkovꢅ, A. Zukal, M. Horꢅ cˇ ek,
ˇ
J. Cejka, ACS Catal. 2011, 1, 709–718.
1050
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1043 – 1051

Olefin Metathesis on a TLC Plate as a Tool for a High-Throughput Screening
˙
[
22] A. Szadkowska, K. Zukowska, A. E. Pazio, K. Wo z´ -
[30] F. C. Courchay, J. C. Sworen, A. Coronado, K. B. Wage-
ner, J. Mol. Catal. A: Chem. 2006, 254, 111–117.
[31] D. Rix, H. Clavier, Y. Coutard, L. Gulajski, K. Grela,
M. Mauduit, J. Organomet. Chem. 2006, 691, 5397–
5405.
niak, R. Kadyrov, K. Grela, Organometallics 2011, 30,
1
130–1138.
[
[
23] A. Kirschning, Ł. Gułajski, K. Mennecke, A. Meyer, T.
Busch, K. Grela, Synlett 2008, 2692–2696.
24] A. Michrowska, Ł. Gułajski, Z. Kaczmarska, K. Men-
[32] D. Rix, F. Caꢈjo, I. Laurent, L. Gulajski, K. Grela, M.
Mauduit, Chem. Commun. 2007, 36, 3771–3773.
necke, A. Kirschning, K. Grela, Green Chem. 2006, 8,
6
85–688.
[
33] E. Borre, C. A. Pieck, F. Caijo, C. Crevisy, M. Mauduit,
[
[
25] K. Grela, M. Kim, Eur. J. Org. Chem. 2003, 6, 963–966.
26] R. Gawin, A. Makal, K. Wo z´ niak, M. Mauduit, K.
Grela, Angew. Chem. 2007, 119, 7344–7347; Angew.
Chem. Int. Ed. 2007, 46, 7206–7209.
27] a) J. Sommer, Y. Yang, D. Rambow, J. Blꢇmel, Inorg.
Chem. 2004, 43, 7561–7563; b) Y. Yang, B. Beele, J.
Blꢇmel, J. Am. Chem. Soc. 2008, 130, 3771–3773.
Chim. Oggi 2009, 27, 74–78.
[
34] Samples of D11–10 can be purchased from the authors
or under http://www.basf.co.kr/02_products/03_chemi-
cals/catalysts&inorganic_chemicals/catalyst_01.html.
35] H. Clavier, S. P. Nolan, Chem. Eur. J. 2007, 13, 8029–
[
[
[
[
8
036.
36] A. Fꢇrstner, L. Ackermann, B. Gabor, R. Goddard,
C. W. Lehmann, R. Mynott, F. Stelzer, O. R. Thiel,
Chem. Eur. J. 2001, 7, 3236–3253.
28] a) S. Gessler, S. Randl, S. Blechert, Tetrahedron Lett.
2
000, 41, 9973–9976; b) S. B. Garber, J. S. Kingsbury,
B. L. Gray, A. H. Hoveyda, J. Am. Chem. Soc. 2000,
22, 8168–8179.
[
37] A. Fꢇrstner, M. Liebl, C. W. Lehmann, M. Piquet, R.
Kunz, C. Bruneau, D. Touchard, P. H. Dixneuf, Chem.
Eur. J. 2000, 6, 1847–1857.
1
[
29] A. Michrowska, R. Bujok, S. Harutyunyan, V. Sashuk,
G. Dolgonos, K. Grela, J. Am. Chem. Soc. 2004, 126,
9
318–9325.
Adv. Synth. Catal. 2012, 354, 1043 – 1051
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1051