Xiang
Hong
a,
Laurianne
Billon
b,
Mohamed
Mellah
*a and
Emmanuelle
Schulz
*ab
aEquipe de Catalyse Moléculaire, ICMMO, UMR CNRS 8182, Université Paris-Sud 11, 91405 Orsay Cedex, France. E-mail: mohamed.mellah@u-psud.fr
bCNRS, Orsay, F-91405, France. E-mail: emmanuelle.schulz@u-psud.fr
First published on 8th November 2012
FeCl3 and NOBF4 have been successfully tested as chemical oxidants to promote the polymerization of thiophene- or pyrrole-modified chiral cobalt salen complexes. The iron oxidation procedure particularly delivered an insoluble polymeric species in nearly quantitative yield that was tested for its propensity to promote the dynamic hydrolytic kinetic resolution of epibromohydrin. This catalyst allowed the synthesis of the expected diol in high yield and up to 85% ee. As an insoluble powder, it was either efficiently recycled in a batch reactor via simple filtration or dispersed in a silica support and reused in a flow procedure for up to five cycles. A copolymerization strategy delivered an even more reliable polymerized complex that was repetitively used without showing any loss in activity or in enantioselectivity for five reuses in this transformation.
In this context, we have described an electrochemical oxidative procedure leading to the synthesis of linear polymers that possessed the chiral metallic salen moiety in the main chain.3 Properly modified salen complexes with thiophene groups at the 5,5′-position were thus synthesized and corresponding chromium- or cobalt complexes were successfully polymerized. Tested as insoluble heterogeneous catalysts, they could promote diverse carbon–carbon or carbon–heteroatom bond formation in hetero Diels–Alder reactions,4 in nitroaldol transformations,5 in dialkylzinc addition to aldehydes, or in the ring-opening of epoxides with various nucleophiles.6
Due to their important chemical and thermal stability associated with a high conductivity, poly(thiophenes) have been developed as organic conducting polymers for numerous applications, such as light-emitting devices, sensor applications, energy storage or thin film transistors.7 These properties are directly linked to the polymeric chain organization and thus to the polymerization conditions. Organometallic couplings leading successfully to structurally well-defined polymers have been described involving Kumada–Corriu,8 Negishi,9 Stille,10 Suzuki11 or Heck-type couplings.12 Oxidative electrochemical polymerization of thiophene derivatives is also well documented,13 and oxidative chemical polymerization reactions have been likewise well reported, which imply monomer oxidation by FeCl3.14 This methodology generally offers a high yield of high molecular weight polymers which have a low amount of irregular couplings.15
Chiral salen cobalt complexes have already demonstrated their undeniable value for promoting the hydrolytic kinetic resolution of epoxides.16 Many efforts were already consequently devoted to their immobilization on various supports for their easy recovery and subsequent reuse.17 Moreover, as detailed mechanistic studies indicated that this transformation was catalysed through a cobalt bimetallic activation,18 targeted oligomeric salen complexes have been prepared aiming at the optimization of the catalyst activity.19 We recently reported that the efficiency of the dynamic hydrolytic kinetic resolution (HKR) of terminal epoxides promoted by electrochemically generated cobalt salen polymers was highly dependent on the polymerization conditions, influencing indeed significantly the polymer structure.20 In relation to these results, we present our efforts towards the synthesis of analogous chiral thiophene–salen cobalt polymers via chemical oxidation and their characterization. These polymers are used here as insoluble, recyclable catalysts to promote the HKR of epibromohydrin not only in a batch reactor but also in a fixed-bed reactor, and preliminary results concerning their use under flow conditions are discussed.
Corresponding cobalt complexes were synthesized according to the reported procedures.21 A Co(II) complex 3 was prepared from ligand 1, which was oxidized in the presence of acetic acid in air to yield Co(III) complex 4, an active catalyst for the dynamic HKR of epibromohydrin.22 Analogously, this procedure, starting from the pyrrole-based ligand 2, afforded Co(III) complex 5 (Fig. 1).
Thiophene–salen cobalt complexes were previously successfully polymerized through electrochemical oxidation. We describe here the ability of complexes 3–5 to be chemically oxidized for the formation of the corresponding polymeric metallic chiral species and their study as catalysts for the dynamic HKR of terminal epoxides.
The general procedures for chemical oxidations are depicted in Scheme 1. Two different oxidizing agents have been tested, FeCl3 and NOBF4, both of which already proved their efficiency in promoting the polymerization of thiophene-based monomers.23,24 The reactions have been performed in chloroform at room temperature under an air or argon atmosphere. The results are gathered in Table 1.
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Scheme 1 A general chemical procedure for chiral cobalt salen polymerization. |
Entry | Monomer | Polymer | Oxidant | Atmosphere | Yield (%) |
---|---|---|---|---|---|
a Monomer 5.0 × 10−2 mol L−1 in CHCl3, 3 h, 10 equiv. oxidants. | |||||
1 | 3 | Poly-3a | FeCl3 | Argon | 80 |
2 | 3 | Poly-3b | FeCl3 | Air | >99 |
3 | 4 | Poly-4a | FeCl3 | Argon | 98 |
4 | 5 | Poly-5a | FeCl3 | Argon | 98 |
5 | 4 | Poly-4b | NOBF4 | Argon | >99 |
6 | 5 | Poly-5b | NOBF4 | Argon | >99 |
Our previous studies have showed that corresponding polymerized Co(III) complexes could be directly prepared from Co(II) precursors under the oxidative electrochemical polymerization conditions.20 Co(II) complex 3 has thus been firstly engaged in the chemical polymerization with an excess of FeCl3 (10 equiv.)25 as an oxidant under an argon atmosphere. After precipitation in MeOH and repeated rinsing with MeOH and THF, the corresponding polymer Poly-3a could be isolated as an insoluble black powder in 80% yield (Table 1, entry 1).
Polymerized 3-alkyl thiophenes with a very high molecular weight have been prepared by Haider et al. by bubbling air through the reaction mixture during the polymerization.26 The polymerization of complex 3 in air has thus been tested, with Poly-3b being recovered with quantitative yield (Table 1, entry 2).
EPR (Electron Paramagnetic Resonance) studies have been carried out to identify the oxidation state of the metal centers in these polymers, with a reported Poly-Co(III) prepared by anodic oxidation as a reference.27 The EPR spectrum of electrogenerated Poly-Co(III) showed a strong signal for the radical (g = 2.002) at 3500 G and also a strong signal for paramagnetic Co(II) at 1500 G, which are in accordance with the reported EPR signals of Jacobsen's Co(III)–OAc complex, as the salen Co(III) complex is in equilibrium with a Co(II) phenoxyl radical species.28 The EPR spectrum of Poly-3b showed no noticeable difference in comparison to that of Poly-Co(III), while a strong signal of Co(II) and a totally negligible signal of radical were observed for Poly-3a. This suggests that metal centers in this polymer are still at the (+II) oxidation state.29
The studies of Poly-3a and Poly-3b by IR spectroscopy have also demonstrated obvious differences in the stretching vibration v(CN). Compared to complex 3 (v(C
N) 1598 cm−1), the v(C
N) band in the IR spectrum of Poly-3b splits into two peaks at 1634 and 1592 cm−1, a phenomenon that was also observed after the oxidation of the Co(II) complex 3 to the Co(III) complex 4 (v(C
N) 1632 and 1607 cm−1).30 However, only one peak was observed for the stretching vibration of Poly-3a (v(C
N) 1609 cm−1), which also tends to prove that metal centers in this polymer stay as Co(II) under the oxidative polymerization conditions.29
The chemical polymerization procedure modifies the oxidation state of the metal centers when a Co(II) complex was used as a monomer, we thus preferred to use preformed Co(III) complexes for the chemical polymerization to ensure the oxidation state of cobalt centers in the polymers.
Complexes 4 and 5 have thus been engaged in chemical polymerization under an argon atmosphere with FeCl3 as an oxidant under the same conditions and Poly-4a and Poly-5a were both obtained with a high yield of 98% (Table 1, entries 3 and 4). NOBF4 has also been proved useful for the polymerization of these two complexes, affording Poly-4b and Poly-5b with nearly quantitative yield (Table 1, entries 5 and 6).
IR spectra of Poly-4a and Poly-4b showed signals similar to those observed for complex 4, two peaks at the stretching vibration region of CN characteristic for Co(III) metal centers in these polymers. However, for Poly-5a and Poly-5b, a complete disappearance of the stretching vibration band at 1737 cm−1 indicates the total decomposition of Boc under the polymerization conditions.29
EDS studies have been performed for Poly-4a and Poly-5a, and signals corresponding to C, N, O, S and Co were also observed. As for Poly-4b and Poly-5b, a relatively high peak of fluorine was also found in the EDS spectrum, which indicated that a part of the Co(III)–OAc complexes might have been transformed to Co(III)–BF4 by anion exchange.31 This has also been confirmed by elemental analysis of Poly-4b, showing that 81% of Co(III)–OAc have been transformed to Co(III)–BF4 during the polymerization.29
All recovered cobalt polymers were engaged to test their ability as promoters for the dynamic HKR of epibromohydrin (Scheme 2). The reaction was performed in THF at room temperature in the presence of 2 mol% of the polymers for 48 hours. The resulting diol was then protected by 2,2-dimethoxypropane to allow the determination of the yield and the enantiomeric excess.
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Scheme 2 Dynamic hydrolytic kinetic resolution of epibromohydrin catalyzed by polymeric cobalt salen complexes. |
The efficiency of complexes 3, 4 and 5 has been previously reported,20 and both Co(III) complexes can catalyse the dynamic HKR of epibromohydrin with good activity and high enantioselectivity under homogeneous conditions (Table 2, entries 2 and 3).
Entry | Catalyst | Yieldb (%) | eec (%) |
---|---|---|---|
a 2 mol% cat., 1.5 equiv. H2O, THF, rt, 48 h. b Isolated yield, determined by the yield of corresponding acetals prepared from 2,2-dimethoxypropane. c Determined by chiral GC analysis of corresponding acetals. d No reaction. | |||
1 | 3 | NRd | — |
2 | 4 | 83 | 92 |
3 | 5 | 75 | 97 |
4 | Poly-3a | NR | — |
5 | Poly-3b | 88 | 83 |
6 | Poly-4a | 76 | 85 |
7 | Poly-5a | 51 | 67 |
8 | Poly-4b | 40 | 25 |
9 | Poly-5b | 57 | 17 |
Poly-3b prepared from 3 under an air atmosphere proved to be an efficient heterogeneous catalyst for the HKR of epibromohydrin, showing similar activity and slightly decreased enantioselectivity in comparison to the monomer complexes (Table 2, entry 5). However, no reaction occurred when Poly-3a obtained from an anaerobic polymerization was tested as a catalyst (Table 2, entry 4). This result exactly matched the observation in EPR and IR analyses of this polymer that Co(II) monomer 3 could not be oxidized to active Co(III) species if the polymerization procedure took place under an argon atmosphere, even in the presence of an excess of FeCl3.32
Poly-4a arising from a pre-formed Co(III)–OAc species led to comparable results to those obtained with Poly-3b, indicating that similar polymeric species might have been prepared through both oxidative procedures (Table 2, entries 5 and 6).33 However, Poly-4b prepared from the same precursor with NOBF4 as an oxidant led to less appealing results in catalysis, which might originate from the unexpected anion exchange during the polymerization (Table 2, entry 8).
Complex 5 has showed good activity and great enantioselectivity in the dynamic HKR of epibromohydrin under homogeneous conditions (Table 2, entry 3). However, poor efficiencies were observed when the corresponding polymerized complexes Poly-5a and Poly-5b were tested under heterogeneous conditions (Table 2, entries 7 and 9). The decreased activity and enantioselectivity probably arose from the loss of the labile protecting Boc group of complex 5 during the polymerization, as was confirmed by IR studies.
Immobilization of catalysts is a great achievement for sustainable development, considering the use of continuous-flow processes. By this strategy, new synthetic methods are economically viable at an industrial scale.34 Indeed, the confinement of the catalyst facilitates the recycling technique by more efficient purification procedures and catalyst regeneration. Moreover in some cases this catalyst immobilization was proved to increase its stability and enantioselectivity.35 Complex 4 could be polymerized chemically with nearly quantitative yield and the resulting polymer Poly-4a showed good activity and enantioselectivity in heterogeneous catalysis. In this context, the application of a fixed-bed reactor was investigated using Poly-4a. The polymer was immobilized through mixing with an octadecyl carbon chain (C18) bonded silica in a reversed phase mode (1/1 w/w). The reversed phase support was preferred to facilitate the release of the diol resulting from the hydrolytic kinetic resolution of epibromohydrin thus preventing fast reactor saturation. The solid support–catalyst mixture was confined in a short HPLC-type pre-column that was thus used as a flow reactor for a new recycling procedure for dynamic HKR of epibromohydrin (Scheme 3). In this home-made reactor the heterogeneous catalytic reaction and the catalyst are perfectly confined and only the desired product and solvent are recovered at the reactor outlet.
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Scheme 3 Dynamic hydrolytic kinetic resolution of epibromohydrin catalyzed by immobilized Poly-4a. |
To adopt the fixed-bed reactor, the HKR of epibromohydrin was realized under diluted conditions: a solution of epibromohydrin in THF (1.1 mol L−1, to insure 2 mol% of catalyst) was introduced and maintained as a constant flow at 1 mL min−1. After 24 hours, 89% of the substrate was hydrolysed to the corresponding diol and the enantiomeric excess of the product was determined to be 81%, values which are totally comparable with those obtained under the classic conditions in a batch reactor.36
As Poly-4a is totally insoluble in the reaction mixture, we thus wondered if this polymeric complex could be reused in successive catalytic runs. Recycling studies of Poly-4a were thus performed in both batch and fixed-bed reactors to evaluate its stability. For the recycling studies in the batch reactor, the polymeric species was simply separated from the product by filtration after the first catalytic run, rinsed with THF, dried under vacuum and reused in a renewed catalytic run by adding new substrates. For the recycling studies in the fixed-bed reactor, the immobilized Poly-4a was rinsed with a flow of dry THF for 30 minutes, and then directly engaged in another run. Five successive catalytic cycles were performed in both cases, and the results are gathered in Tables 3 and 4.
Run | Conv.b (%) | eec (%) |
---|---|---|
a 9.08 mmol of epibromohydrin in 8 mL of THF in order to insure 2 mol% of catalyst. b Conversion determined by GC analysis after 24 h, with chlorobenzene as an internal standard. c Determined by chiral GC analysis of corresponding acetals. | ||
1 | 89 | 81 |
2 | 74 | 78 |
3 | 71 | 74 |
4 | 54 | 69 |
5 | 48 | 71 |
Poly-4a proved delightfully to be an efficient promoter for the repetitive transformation of epibromohydrin in the batch procedure. The desired product could be obtained at each cycle, with high and stable values of enantiomeric excess. However, continuing decreased yields showed that this catalyst deactivated along the recycling studies, although it is still not clear whether the mechanical or the chemical instability of Poly-4a is responsible for the decrease of its activity in this recycling procedure.
As for the recycling studies in the fixed-bed reactor, stable enantiomeric excesses of the expected product were again observed (71% ee after the 5th run). The average enantioselectivity value is however slightly diminished in comparison to the one observed in the batch procedure, and an influence of the catalyst support on the course of the enantioselective transformation cannot be excluded. In this case again, large variations in the conversion (from 89% to 48% at the last run) went along with the recycling. The similarly decreased efficiency of Poly-4a in the fixed-bed reactor indicated that the deactivation of this catalyst should arise from its chemical structural alteration during the HKR.
Mechanistic studies of the HKR by Jacobsen et al. showed that a mixture of salen Co(III) complexes containing both nucleophilic and non-nucleophilic counter anions is more efficient than the classic Co(III)–OAc catalyst,18 and we previously prepared a stable heterogeneous catalyst for the HKR by the electrochemical copolymerization of a salen Co(III)–OAc complex and a salen Co(III)–BF4 complex.20 In order to enhance the stability of the chemically generated polymers, we wondered if the copolymerization strategy could also be applied to the chemical polymerization. Towards this aim, complex 6 was synthesized in high yield from Co(II) complex 3 through oxidation with ferrocenium tetrafluoroborate,37 and a copolymerization test was performed by mixing an equimolar amount of monomers 4 (Co(III)–OAc sites) and 6 (Co(III)–BF4 sites) in the presence of FeCl3 as an oxidant (Scheme 4).
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Scheme 4 A chemical oxidative procedure for the synthesis of chiral Poly-4/6. |
Poly-4/6 was also recovered as an insoluble powder after methanol washings in 90% yield. Elemental analyses were performed for the determination of the Co, B and F contents, and the percentage of Co(III)–BF4 in the resulting copolymer was determined to be 49%. This copolymer was tested for the dynamic HKR of epibromohydrin under the same conditions, allowing the formation of the corresponding diol in good yield (75%) and high enantiomeric excess (80%) after 48 hours. To test the stability of the polymeric structure during the HKR transformation, repetitive experiments following the same procedures as those performed to study the stability of Poly-4a were achieved, and the results obtained are gathered in Tables 5 and 6.
Run | Conv.b (%) | eec (%) |
---|---|---|
a 9.08 mmol of epibromohydrin in 8 mL of THF in order to insure 2 mol% of catalyst. 2 mol% cat., 2 equiv. H2O, rt, 48 h. b Conversion determined by GC analysis after 24 h, with chlorobenzene as an internal standard. c Determined by chiral GC analysis of corresponding acetals. | ||
1 | 72 | 74 |
2 | 76 | 76 |
3 | 81 | 75 |
4 | 80 | 78 |
5 | 83 | 76 |
In contrast to the catalytic results reported for Poly-4a in Tables 4 and 5, Poly-4/6 allowed the repetitive preparation of the scalemic diol with stable high yields and high enantiomeric excesses for both batch and fixed-bed procedures. These values remained furthermore stable, as a clear differentiation in the catalytic behaviour of both polymers. The yield fluctuation was indeed no more noticeable for the catalysis promoted by Poly-4/6. Even after the last cycle, the product was still isolated in a high yield of more than 80%, whatever the recycling methodology. The structures of Poly-4a and Poly-4/6 only differ in the axial ligands of the cobalt atoms. As already demonstrated by the studies of Jacobsen et al.,18 the cobalt complex bearing acetate as an axial ligand undergoes irreversible hydrolysis to CoIII–OH species in the HKR, which leads to the deactivation of the catalyst during the reaction. This formation of CoIII–OH sites during the catalysis performed by Poly-4a may be an explanation for its deactivation along with its recycling. In the case of Poly-4/6 possessing both nucleophilic and non-nucleophilic active sites, such a deactivation is presumably prevented to allow its repeated efficient use.
To determine the extent of applications of Poly-4/6, this insoluble catalyst was used in a batch procedure for promoting successively the hydrolytic kinetic resolution of different terminal epoxides, by changing the structure of the substrate at each reuse of the polymer. A first run was then devoted to the already studied HKR of epibromohydrin yielding the expected results (see Table 7, run 1). The recovered catalyst was then engaged in the transformation of 2-phenoxymethyloxirane (Table 7, run 2).38
Run | Epoxide | Time (h) | Yielda (%) | ee (%) |
---|---|---|---|---|
a GC yield, determined by achiral GC analysis with chlorobenzene as an internal standard. b 2 mol% cat., 1.5 equiv. H2O, THF, RT. c 0.5 mol% cat., 0.65 equiv. H2O, RT. d 0.8 mol% cat., 0.65 equiv. H2O, THF, RT. e Determined by chiral GC analysis (Chiraldex β-PM, 110 °C isothermal). f Determined by chiral HPLC analysis (Chiralcel OD-H, Hex/iPrOH 95/5, 1.0 mL min−1, 214 nm, 25 °C). g Determined by chiral GC analysis (Chiraldex β-PM, 35 °C isothermal). h Determined by chiral GC analysis (Chiraldex β-PM, 110 °C, 10 min, 10 °C min−1 up to 170 °C). i Theoretical yield = 50%. | ||||
1b | Epibromohydrin | 48 | 75 | 80e |
2c | 2-Phenoxymethyl-oxirane | 48 | 38i | 99f |
3c | 2-Allyloxymethyl-oxirane | 48 | 41i | 99g |
4d | 2-Phenyloxirane | 64 | 45i | 85h |
5 | Epibromohydrin | 48 | 89 | 85 |
The subsequent recycling procedure engaged consecutively 2-allyloxymethyloxirane and 2-phenyloxirane and the last run was assigned again to the hydrolysis of epibromohydrin. Albeit the heterogeneous catalysis proved to be less efficient in terms of activity for the transformations of the new substrates in comparison to the results obtained under homogeneous conditions (Table 7, runs 2–4), nearly enantiopure products could nevertheless be obtained in two cases with higher substrate conversion after prolonged reaction time. Finally, Poly-4/6 was reused a fifth time for the dynamic HKR of epibromohydrin (Table 7, run 5), delivering interestingly an improved activity and enantioselectivity in comparison to the first run. Detailed kinetic studies were realized for the first run and the fifth reuse of this polymer and no obvious difference was observed.29 Together with a supplementary experiment proving no metal leaching,39 this undoubtedly demonstrated the stability of this easily prepared polymer in the HKR.
As far as we know, this report is the first demonstration of the efficient use of a heterogeneous catalyst generated as a polymeric structure through chemical oxidation, involved successfully in repetitive asymmetric transformations. This simple procedure requiring only cheap and easily accessible oxidants could be applied to the heterogenization of other chiral metallic complexes, or even their corresponding ligands, opening the way of an economic and environmentally benign use (and reuse) of valuable asymmetric catalysts. Work towards this end is in progress in our laboratory.
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c2cy20644g |
This journal is © The Royal Society of Chemistry 2013 |