Grubbs Catalysts Immobilized on Merrifield Resin for Metathesis of Leaf Alcohols by using a Convenient Recycling Approach

Article abstract of DOI:10.1002/open.201800188

Three new types of heterogeneous catalysts were prepared using a facile approach by the immobilization of Grubbs catalysts on PEGylated Merrifield resin. One of the immobilized catalysts was more efficient than the free catalyst for the metathesis of leaf alcohols in conversion and selectivity and was reused repeatedly (up to 5 cycles) with only a slight loss of activity (10.5 %). The long-chain PEGylated linker provided an appropriate distance between the resin and the catalytic center so that the ruthenium catalysts acted as the free catalyst.

Full text of DOI:10.1002/open.201800188

Communications
DOI: 10.1002/open.201800188
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Grubbs Catalysts Immobilized on Merrifield Resin for
Metathesis of Leaf Alcohols by using a Convenient
Recycling Approach
Liang Xia+,[a, b] Tao Peng+,[b] Gang Wang,[b] Xiaoxue Wen,[b] Shouguo Zhang,*[b] and
Lin Wang*[a, b]
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divided into homogeneous and heterogeneous categories
according to their status in the reaction solution. Many
homogeneous carrier loaded Grubbs catalysts were reported.
For example, Matthew Sheets and Marc Mauduit immobilized
Hoveyda Grubbs catalysts on ionic liquids for olefin metathesis
with high efficiency.[7–9] Gravert and Harwig immobilized
Hoveyda Grubbs catalysts on Polyethylene glycol (PEG) for ring
closing metathesis (RCM) reactions with high efficiency.[10]
However, the recycling procedures of these homogeneous
catalysts were tedious and time-consuming. Many heteroge-
neous carrier loaded Grubbs catalysts were also reported. For
example, Robert H. Grubbs immobilized RuCl2 (=CHCH=CPh2)
(PPh3)2 on polystyrene-divinylbenzene (PS-DVB) for Ring-Open-
ing Metathesis Polymerization (ROMP) reactions of cyclic
olefins.[11] Michal Bieniek immobilized Hoveyda Grubbs catalyst
on butyldiethylsilyl polystyrene (PS-DES) for metathesis of
substituted olefins.[12] Robert H. Grubbs immobilized Hoveyda
Grubbs catalysts on silica gel for a number of metathesis
reactions.[13] There are also some reports about using new kinds
of supports, such as magnetic nanoparticle, mesoporous
molecular silicas and aluminas, to immobilize Grubbs catalysts
for metathesis.[14–16] These results showed that the heteroge-
neous catalysts were recycled conveniently over a number of
reaction cycles. However, they were prepared with long
reaction steps and some of them had longer reaction times,
lower conversions and catalytic activities than free catalysts.
In sum, heterogeneous catalysts showed comparative
advantages in recycling, which indicated that immobilization on
proper solid support could help the Grubbs catalysts recycle
efficiently. Inspired by linker strategy in solid phase synthesis,
the immobilization strategy should be optimized by keeping a
long distance between solid support and catalyst. Merrifield
resin was a good heterogeneous support with good swelling
and recycling activity. PEG linker was a polymer that was
soluble in many solvents. Merrifield resin and PEG linker could
act as the proper support and linker. Next, it was important to
select a proper catalyst as a supported research object. 1,3-bis
(2,4,6-trimethylphenyl)-2-imidazolidinylidene)(3,6-dichlorophen-
yl[d][2, 7]dithio)(o-isopropoxyphenylmethylene) ruthenium (Ru-
3b, 7) was developed from Hoveyda Grubbs catalyst with high
Z/E selectivity for many substrates.[17] We hoped to immobilize
Ru-3b on Merrifield resin through PEG linker but there were no
connection sites in the catalyst structure. In this paper, three
similar catalysts (7a, 7b and 7c) of Ru-3b were designed and
synthesized, phenolic hydroxyl or mercapto were used as
immobilization sites. Therefore three supported catalysts (Ru-a,
Three new types of heterogeneous catalysts were prepared
using a facile approach by the immobilization of Grubbs
catalysts on PEGylated Merrifield resin. One of the immobilized
catalysts was more efficient than the free catalyst for the
metathesis of leaf alcohols in conversion and selectivity and
was reused repeatedly (up to 5 cycles) with only a slight loss of
activity (10.5%). The long-chain PEGylated linker provided an
appropriate distance between the resin and the catalytic center
so that the ruthenium catalysts acted as the free catalyst.
Alkenes could be prepared by olefin metathesis reactions which
were initiated by re-combination of two pairs of original olefin
carbon-carbon double bonds to form two new pairs of carbon-
carbon double bonds. Grubbs catalysts were widely used for
olefin metathesis reactions. Various Grubbs catalysts were
reported up to now. First generation of Grubbs catalyst (GI) was
resistant against oxygen and water. However, it was prone to
decompose at high temperature.[1,2] Second generation of
Grubbs catalyst (GII) was prepared with improved thermal
stability and catalytic activity.[3,4] Unfortunately, it was sensitive
to water and oxygen.[5] Although Grubbs catalysts made great
progress in catalytic efficiency and selectivity, the expensive
price limited their applications.
As homogeneous catalysts, recycling Hoveyda Grubbs
[6]
catalysts for reuse were very difficult.
In order to improve
their recovery, Grubbs catalysts were connected to different
supports to prepare supported catalysts, which would be
[a] Dr. L. Xia,+ Prof. L. Wang
Beijing University of Technology
College of Life Science and Bio-engineering Department
Beijing, 100124 (P. R. China)
E-mail: xlxialiang12345@163.com
wanglin@bmi.ac.cn
[b] Dr. L. Xia,+ Dr. T. Peng,+ Dr. G. Wang, X. Wen, Dr. S. Zhang, Prof. L. Wang
Beijing Institute of Radiation Medicine
Beijing, 100850 (P. R. China)
E-mail: pengtao@bmi.ac.cn
zhangshouguo1409@sina.com
wanglin@bmi.ac.cn
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/open.201800188
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This
is an open access article under the terms of the Creative Commons Attri-
bution Non-Commercial NoDerivs License, which permits use and distribu-
tion in any medium, provided the original work is properly cited, the use is
non-commercial and no modifications or adaptations are made.
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Communications
etherification of 7a with 6, total yield=59.7%, calculated
loading rate=3.05×10À 3 mmol/g (Ru), which was calculated by
formula L×(W’-W)/ (W’’-W), L: loading rate of Merrifield resin,
W: original weight of Merrifield resin, W’: actual weight of Ru-a,
W’’: theoretical weight of Ru-a. Elemental analysis showed 1 g
Ru-a loaded 0.32 mg ruthenium. Loading rate of Ru-a (Ru/g)
was 3.17×10À 3 mmol/g after calculation. Comparing with the
Infrared Spectroscopy (IR) of 6, appearance of methyl and
benzene signals showed that 7a had been loaded on 6. The
detailed IR was shown as follows: 2846~2920 (CH2), 3024~3058
(CH3), 1739 (alkene), 1421, 1492, 1510, 1600 (benzene).
Ru-b and Ru-c were prepared and characterized according
to Ru-a. Ru-b: yield=63.4%. Elemental analysis showed 1 g Ru-
b loaded 1.0 mg ruthenium. Characterized loading rate=9.96×
10À 3 mmol/g. Calculated loading rate=9.90×10À 3 mmol/g).
Appearance of methyl, hydroxyl and benzene signals showed
that 7b had been loaded on 6. IR: 3448.41 (s, OH), 2850~2918
(d, CH2), 3058~3081 (d, CH3), 1664 (s, alkene), 1450, 1510, 1544,
1600 (q, benzene).
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Scheme 1. Design of the three supported catalysts.
Ru-b, Ru-c) were prepared by immobilizing 7a, 7b and 7c on
PEGylated Merrifield resin (6; Scheme 1). These catalysts were
expected to be recycled efficiently while maintaining the high
Z/E stereoselectivity as the free catalyst.
(Z)-hex-3-ene-1, 6-diol was an important intermediate which
was prepared by a long route including drastic oxidation
reaction.[18,19] In our work (Z)-hex-3-ene-1, 6-diol was prepared
efficiently by catalyzing leaf alcohols with Ru-3b and the new
catalysts (Ru-a, Ru-b and Ru-c). As we expected, three new
catalysts showed similar catalytic activities to Ru-3b. Ru-b was
better than Ru-a and Ru-c in catalytic activities and conversions.
Recycling experiments showed that Ru-b could be reused for
more than 5 times in recycling.
The solid phase catalysts were designed as three parts. The
first part and second part were Merrifield resin and PEG
polymer. They acted as the support and linker. Pseudo-dilution
effect of Merrifield resin and good solubility of PEG polymer in
many solvents ensured the catalytic activities. The third part
was the Grubbs catalyst. Similar structures of Ru-3b were
prepared. The specific design was as follows: 7a retained the
main structure of Ru-3b, 1-isopropoxy-2-vinylbenzene was
replaced by 2-vinylphenol as the oxonium group. The phenolic
hydroxyl group of the oxonium group was regarded as the
connection site. Ru-a was prepared by etherification of
PEGylated resin (6) and the exposed phenolic hydroxyl group in
7a. 7b introduced a phenolic hydroxyl group on the carbene
structure (4 and 4’ positions) by replacing raw material 2, 4, 6-
trimethylaniline with 4-amino-3, 5-dimethylphenol. Phenolic
hydroxyl group served as the attachment site of 7b. Ru-b was
prepared by connection of 7b and 6. 7c was designed based
on Ru-3b. Mercapto group was introduced on the benzene ring
complexed with dithiole. The original chlorine groups were not
retained on the benzene. Ru-c was prepared by connection of
7c and 6 (Scheme 1).
Ru-c: yield=53.7%, elemental analysis showed 1 g Ru-c
loaded 0.47 mg ruthenium, characterized loading rate=4.63×
10À 3 mmol/g. Calculated loading rate=4.50×10À 3 mmol/g. Ap-
pearance of methyl, methylene and benzene signals showed
that 7c had been loaded on 6. IR: 2856~2920 (d, CH2), 3058~
3081 (d, CH3), 1739 (s, alkene), 1421, 1492, 1510, 1600 (q,
benzene) (Scheme 2).
Leaf alcohols were catalyzed with Ru-3b, Ru-a, Ru-b and
Ru-c. A solution of Z or E leaf alcohol and Ru-3b in
°
tetrahydrofuran (THF) was shaken for 10 h at 25 C. Mixtures of
products were gained via silica gel chromatography [Petroleum
ether (PE): Ethyl Acetate (EA)=20:1]. Z/E ratios of the mixtures
[(Z)-hex-3- ene-1, 6-diol and (E)-hex-3-ene-1, 6-diol)] were calcu-
1
lated according to H NMR results. The reaction conditions of
Ru-a, Ru-b or Ru-c catalyzing leaf alcohols were the same as
Ru-3b, yields and Z/E ratios of products were shown in Table 1.
Table 1. Catalysis of (Z) leaf alcohol or (E) leaf alcohol with Ru-3b, Ru-a,
Ru-b or Ru-c.
Entry[a]
Substrate
Catalyst
Yield
Ratio (Z/E)
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2
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4
5
6
7
8
Z leaf
E leaf
Z leaf
E leaf
Z leaf
E leaf
Z leaf
E leaf
Ru-3b
Ru-3b
Ru-a
Ru-a
Ru-b
Ru-b
Ru-c
46.0%
62.3%
35.1%
73.2%
50.0%
75.0%
45.6%
63.8%
90:10
14:86
88:12
23:77
92:8
3:97
88:12
Ru-c
11:89
[a] Group.
Ru-3b (7) was prepared according to literatures.[20–24] (details
see supporting information). 7a, 7b and 7c were prepared
from similar raw materials by complexation reaction. 5 was
prepared from Merrifield resin (The Cross-Linking degree (%
DVB)=1%, Particle size=100 mesh, Loading rate=0.52 mmol/
L) and PEG 200 by etherification under microwave. 6 was
prepared from 5 by Appel reaction. Ru-a was prepared by
The control experiment was carried out with 6 instead of three
catalysts. The reaction solution was analyzed by HPLC, showing
that 6 had no catalytic efficiencies.
Results showed that a high ratio of Z/E product was gained
with Z leaf alcohol as the raw material. On the contrast, a high
ratio of E/Z product was gained with E leaf alcohol as the raw
material. When Z leaf alcohol was substrate, the product of Ru-
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Scheme 2. Synthetic route for the preparation of the three supported catalysts.
b group showed higher Z/E ratio than products of other three
groups. When E leaf alcohol was catalytic substrate, the product
of Ru-b group showed higher E/Z ratio than products of other
three groups (Table 1). Showing that Ru-b was more efficient
than Ru-3b, Ru-a and Ru-c. There were three explanations for
this. (1) Compared with Ru-a, the immobilization center of Ru-b
was farther from its catalytic center. (2) Low efficiency of Ru-c
might due to lack of chlorine group in the benzene compared
with Ru-3b. (3) Compared with Ru-3b, hydroxyl on the carbene
of Ru-b was an electronic donating group which might improve
its catalytic activity.
With Z leaf alcohol as substrate, single recycling experi-
ments of Ru-a, Ru-b and Ru-c were performed respectively.
Recovery efficiencies were calculated by formula: W’/W, W’:
recycling weight of the catalysts. W: original weight of the
catalysts. Recovery efficiency and yield of Ru-b was higher than
that of Ru-a and Ru-c (Table 2). Therefore Ru-b was selected for
the multiple recycling experiments. Z leaf alcohol was catalyzed
by Ru-b for 5 cycles. The catalytic results were analyzed by
HPLC. Results showed that Entry 1–4 had high recovery
efficiencies (>80%), Entry 5 had low recovery efficiency which
might due to large filter loss. Conversions (>35%) and Z
product ratio (>85%) decreased gradually as we expected
(Table 3).
Grubbs catalysts were immobilized on various carriers for
multiple catalysis. Inspired by the role of linker in solid phase
synthesis, three new Grubbs catalysts immobilized on PEGylated
Merrifield resin were prepared for metathesis of leaf alcohols.
Multiple recycling experiments were performed by catalyzing Z
leaf alcohol with Ru-b for 5 cycles. Recovery efficiencies, yields
and Z/E ratios were calculated and the results showed the
conclusions as follows: (1) Results of leaf alcohols catalyzed by
four catalysts showed that cis-products were obtained mainly
when the cis-based materials were used for catalysis. Trans-
products were obtained mainly when the trans-type raw
materials were used for catalysis. (2) PEG linker strategy was
successful, three catalysts showed similar activities to Ru-3b
with convenient recycling approach, Ru-b was the best catalyst
for metathesis of leaf alcohols which could be reused for more
than 5 times. (3). (Z)-hex-3-ene-1, 6-diol was prepared from leaf
alcohol by olefin metathesis reaction, which promoted the
application of Grubbs catalysts. The catalysts will be used for
more substrates, and our work might provide a new idea for
immobilization of other catalysts.
Table 2. Recovery of Ru-a, Ru-b and Ru-c.
Entry[a]
Substrate
Catalyst
Yield
Ratio (Z/E)
1
2
3
Z leaf
Z leaf
Z leaf
Ru-a
Ru-b
Ru-c
37.3%
57.6%
50.3%
69:31
92:8
88:12
[a] Group.
Table 3. Recovery efficiencies of Ru-b (repeated five times).
Entry[a]
Substrate
Catalyst
Yield
Ratio (Z/E)
Experimental Section
For experimental details please see the Supporting Information.
1
2
3
4
5
Z leaf
Z leaf
Z leaf
Z leaf
Z leaf
Ru-b
Ru-b
Ru-b
Ru-b
Ru-b
57.6%
50.5%
48.3%
40.0%
36.9%
95:5
92:8
90:10
88:12
85:15
[a] Group.
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Communications
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This work is supported by National Natural Science Foundation
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Conflict of Interest
The authors declare no conflict of interest.
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Keywords: leaf alcohols
recycling · supported catalysts
· Merrifield resin · metathesis ·
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Manuscript received: September 8, 2018
Revised manuscript received: November 8, 2018
Version of record online: ■■■, ■■■■
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