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

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 catalysts for reuse were very difficult. [6] In order to improve their recovery, Grubbs catalysts were connected to different supports to prepare supported catalysts, which would be 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, 8, 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 heterogeneous 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‐Opening 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, 15, 16 These results showed that the heterogeneous 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‐dichlorophenyl[d][2, 7]dithio)(o‐isopropoxyphenylmethylene) ruthenium (Ru‐3 b, 7) was developed from Hoveyda Grubbs catalyst with high Z/E selectivity for many substrates.17 We hoped to immobilize Ru‐3 b on Merrifield resin through PEG linker but there were no connection sites in the catalyst structure. In this paper, three similar catalysts (7 a, 7 b and 7 c) of Ru‐3b were designed and synthesized, phenolic hydroxyl or mercapto were used as immobilization sites. Therefore three supported catalysts (Ru‐a, Ru‐b, Ru‐c) were prepared by immobilizing 7 a, 7 b and 7 c 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.

Scheme 1

Design of the three supported catalysts.

(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‐3 b. 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‐3 b were prepared. The specific design was as follows: 7 a retained the main structure of Ru‐3 b, 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 7 a. 7 b 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 7 b. Ru‐b was prepared by connection of 7 b and 6. 7 c was designed based on Ru‐3 b. 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 7 c and 6 (Scheme 1).

Ru‐3 b (7) was prepared according to literatures.20, 21, 22, 23, 24 (details see supporting information). 7 a, 7 b and 7 c 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 etherification of 7 a with 6, total yield=59.7 %, calculated loading rate=3.05×10−3 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 3.17×10−3 mmol/g after calculation. Comparing with the Infrared Spectroscopy (IR) of 6, appearance of methyl and benzene signals showed that 7 a 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=9.96×10−3 mmol/g. Calculated loading rate=9.90×10−3 mmol/g). Appearance of methyl, hydroxyl and benzene signals showed that 7 b 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).

Ru‐c: yield=53.7 %, elemental analysis showed 1 g Ru‐c loaded 0.47 mg ruthenium, characterized loading rate=4.63×10−3 mmol/g. Calculated loading rate=4.50×10−3 mmol/g. Appearance of methyl, methylene and benzene signals showed that 7 c 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).

Scheme 2

Synthetic route for the preparation of the three supported catalysts.

Leaf alcohols were catalyzed with Ru‐3 b, Ru‐a, Ru‐b and Ru‐c. A solution of Z or E leaf alcohol and Ru‐3 b 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 calculated according to 1H NMR results. The reaction conditions of Ru‐a, Ru‐b or Ru‐c catalyzing leaf alcohols were the same as Ru‐3 b, yields and Z/E ratios of products were shown in Table 1. 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.

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)
1	Z leaf	Ru‐3b	46.0 %	90 : 10
2	E leaf	Ru‐3b	62.3 %	14 : 86
3	Z leaf	Ru‐a	35.1 %	88 : 12
4	E leaf	Ru‐a	73.2 %	23 : 77
5	Z leaf	Ru‐b	50.0 %	92 : 8
6	E leaf	Ru‐b	75.0 %	3 : 97
7	Z leaf	Ru‐c	45.6 %	88 : 12
8	E leaf	Ru‐c	63.8 %	11 : 89

[a] Group.

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‐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‐3 b, 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‐3 b. (3) Compared with Ru‐3 b, 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 experiments 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).

Table 2

Recovery of Ru‐a, Ru‐b and Ru‐c.

Entry[a]	Substrate	Catalyst	Yield	Ratio (Z/E)
1	Z leaf	Ru‐a	37.3 %	69 : 31
2	Z leaf	Ru‐b	57.6 %	92 : 8
3	Z leaf	Ru‐c	50.3 %	88 : 12

[a] Group.

Table 3

Recovery efficiencies of Ru‐b (repeated five times).

Entry[a]	Substrate	Catalyst	Yield	Ratio (Z/E)
1	Z leaf	Ru‐b	57.6 %	95 : 5
2	Z leaf	Ru‐b	50.5 %	92 : 8
3	Z leaf	Ru‐b	48.3 %	90 : 10
4	Z leaf	Ru‐b	40.0 %	88 : 12
5	Z leaf	Ru‐b	36.9 %	85 : 15

[a] Group.

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.

Experimental Section

For experimental details please see the Supporting Information.

Conflict of interest

The authors declare no conflict of interest.

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Supplementary

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