Pt nanoparticles stabilized by thermosensitive polymer as effective and recyclable catalysts for the asymmetric hydrogenation of ethyl pyruvate

Abstract

Thermosensitive and thiol-terminated poly(N-isopropylacrylamide)s (PNIPAM-SHs) were synthesized and used to stabilize Pt nanoparticles. After chiral modification with cinchonidine, these nanocatalysts were firstly applied in the asymmetric hydrogenation of ethyl pyruvate. The influences of reaction solvent, chiral modifier concentration, hydrogen pressure, mean molecular weight and amount of polymer on the catalytic performance were investigated. These colloidal Pt catalysts exhibited remarkably high catalytic activity and enantioselectivity. Especially, high turnover frequencies up to 17 820 h⁻¹ were achieved, which is the best result for this reaction with regard to the colloidal Pt catalysts. The high catalytic activity was associated with the high hydrophobicity of isopropyl groups in polymer moieties in the catalyst. Moreover, recycling experiments showed that the thermosensitivity of PNIPAM-SH made these colloidal Pt catalysts easier to recover and reuse. Excellent stability and reusability were presented over these catalysts, and no obvious decrease in catalytic activity and enantioselectivity was observed for eleven runs.

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1. Introduction

The catalytic enantioselective hydrogenation of α-functionalized ketones to the corresponding chiral alcohols has received extensive attention because the reaction products are widely used synthetic intermediates for pharmaceuticals, agrochemicals, food additives, perfumed cosmetics, and so on.^1,2 Since it was discovered in 1979 by Orito et al.,^3,4 the cinchona alkaloid modified Pt catalyst for the asymmetric hydrogenation of α-ketoesters has been considered as one of the most effective and promising heterogeneous asymmetric hydrogenation catalytic systems.⁵ Substantial research has centered on this system and remarkable progress has been achieved in the past decades.^6–9 Among the supported Pt catalysts, commercial Pt/Al₂O₃ has been most widely studied^10–15 and could give excellent results in terms of enantiomeric excesses (ees) after pretreatment in flowing hydrogen at elevated temperature¹⁶ or sonication.¹⁷ Except for limited examples,^18–21 Pt particles supported on other solid materials^22–33 exhibited inferior catalytic performance compared to Pt/Al₂O₃. Nevertheless, the catalytic properties of Pt/Al₂O₃ were found to markedly depend on the dispersion of Pt particles as well as the synthetic process of the catalyst.² On the other hand, colloidal Pt catalysts modified have attracted increasing attention^34–39 due to their recognized advantages such as the elimination of the support effects, and the controllability in sizes and shapes of metal particles.^2,37 Bönnemann et al. firstly applied Pt colloid for the asymmetric hydrogenation of ethyl pyruvate using protonated dihydrocinchonidine as stabilizer and chiral modifier,³⁴ yielding products with an ee of around 80%. The polyvinylpyrrolidone-stabilized Pt colloid was reported by Liu et al.³⁵ for the asymmetric hydrogenation of α-ketoesters and excellent enantioselectivities were achieved, but there was no details about the recovery and reusability of this colloidal catalyst. The surfactant was also utilized as stabilizer of Pt nanoparticles,³⁷ the resulting catalytic system could be recycled three times and up to 55% ee was obtained for the asymmetric hydrogenation of ethyl pyruvate in aqueous phase. Haag et al. presented the asymmetric hydrogenation of ethyl pyruvate with Pt nanoparticles homogeneously stabilized in dendritic core–multishell architectures³⁸ and 63% ee was attained at 7.0 MPa hydrogen pressure. After further stabilization with extra polymer, this catalyst could be recycled by ultrafiltration for eight runs with stable activity and increased enantioselectivity (73% ee). Up to now, however, there were few reports about colloidal Pt catalysts that combined high enantioselectivity and reusability. It is greatly desirable to develop a new Pt colloid system of high catalytic performance, simple recovery and high reusability.

As a typical temperature-sensitive polymer, poly(N-isopropylacrylamide) (PNIPAM) has recently attracted considerable interest owing to its promising applications such as rheology modifications,⁴⁰ targeted drug delivery⁴¹ and catalysis.^42–45 PNIPAM has a lower critical solution temperature (LCST) of ∼32 °C at which the polymer undergoes a change from a coil (soluble) conformation to a globule (insoluble) state in water.⁴⁶ In addition, PNIPAM exhibits cononsolvency in mixed aqueous solutions,^47,48 namely, the LCST of PNIPAM is depressed in the presence of an appropriate proportion of water-miscible polar organic solvents such as methanol, ethanol, tetrahydrofuran. Thus, PNIPAM is insoluble in the mixed solution at room temperature and even lower temperatures though it is well soluble in both pure solvents separately. This unique property of PNIPAM provides a convenient alternative to recover nanocatalysts in either aqueous or organic media.

Here we wish to explore the PNIPAM-stabilized colloidal Pt catalyst for the asymmetric hydrogenation of ethyl pyruvate. In this work, Pt nanoparticles of ca. 1.8 nm were prepared and surface-grafted by PNIPAM bearing a thiol group at the chain end (PNIPAM-SH). These polymer-modified Pt nanocatalysts would combine the merits of both metal colloidal catalyst and thermosensitive polymer. High catalytic performance was expected over these catalysts due to the easy accessibility of active centers in metal colloidal catalytic system as well as the high hydrophobicity of isopropyl groups in polymer molecules, which is advantageous to the adsorption of substrates onto the catalyst. In addition, these Pt nanocatalysts were also expected to be easily recoverable and highly durable owing to the good thermosensitivity of PNIPAM and the strong interaction between the thiol groups in polymer molecules and unsaturated surface of Pt nanoparticles.

2. Experimental

2.1 General

Hexachloroplatinic acid hexahydrate (H₂PtCl₆·6H₂O, AR, Aldrich), cinchonidine (98%, Aldrich), and ethyl pyruvate (99%, Aldrich) were used as received. N-Isopropylacrylamide (NIPAM, 98%, Aldrich) was recrystallized from hexane before use. 2,2-Azobisisobutyronitrile (AIBN, AR, Wako Pure Chemical Ind., Ltd.) was recrystallized from ethanol and dried under vacuum.

¹H NMR spectra were recorded at 300 MHz using a Varian Mercury Vx-300 spectrometer. IR spectra of the catalysts were taken in transmission mode by using a Bruker Tensor 27 Fourier transform IR (FT-IR) instrument. The elemental analysis of C, H and N was performed on a Perkin-Elmer 240C analyzer. Gel permeation chromatography (GPC) analysis was carried out on a GPC system equipped with a Waters 1525 pump, a Waters 2414 differential refractometer, a series of three linear Styragel columns HT2, HT3, and HT4, and a control module to set the temperature (typically at 35 °C). Tetrahydrofuran was used as eluent at a flow rate of 1.0 mL min⁻¹ and a series of low polydispersity polystyrenes were employed as calibration standards. Transmission electron microscopy (TEM) images were obtained on a Philips Tecnai G²F20 electron microscope with an accelerating voltage of 200 kV. Samples were prepared by depositing a small drop of the colloidal dispersion in ethanol onto a copper grid covered with carbon film and dried in air. The contents of Pt in the catalysts and Pt leaching in the reaction solution were determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES) on an ICP-9000(N+M) spectrometer (TJA Co.). Conversions and ee values were determined by GC equipped with a flame ionization detector and a RESTEC RT-BetaDEXse chiral capillary column (30 m × 0.25 mm × 0.25 μm). The column temperature was set at 80 °C. The enantioselectivity is expressed as ee (%) = 100 × ([R] − [S])/([R] + [S]).

2.2 Synthesis of PNIPAM stabilized Pt nanoparticles

2.2.1 Synthesis of RAFT agent cumyl dithiobenzoate (CDB). Firstly, as shown in Scheme 1, dithiobenzoic acid was synthesized from the reaction of benzyl chloride and sublimed sulfur as reported in the literature.⁴⁹ Then CDB was synthesized following a method similar to that of Oae et al.⁵⁰ Specifically, dithiobenzoic acid (3.0 g, 19.4 mmol) was reacted with α-methylstyrene (3.0 mL, 23.1 mmol) in the presence of p-toluenesulfonic acid (0.1 g) as catalyst in carbon tetrachloride (40 mL) under stirring. The reaction was conducted at 70 °C for 12 h. The crude product was obtained after solvent evaporation and subsequently purified by column chromatography on silica gel (petroleum ether) to give CDB in dark purple. ¹H NMR (300 MHz, CDCl₃): δ (ppm) 2.00 (s, 6H), 7.16–7.22 (m, 1H), 7.29 (t, 4H), 7.40–7.47 (m, 1H), 7.52 (d, 2H), 7.82 (dd, 2H). FT-IR: 1223 cm⁻¹ (C–S), 1047 cm⁻¹ (C=S).

Scheme 1 Syntheses of RAFT agent CDB and PNIPAM-SHx.

2.2.2 Synthesis of thiol-terminated PNIPAM by RAFT polymerization. As shown in Scheme 1, dithiobenzoate-terminated PNIPAM was synthesized by RAFT polymerization using CDB as RAFT agent and AIBN as initiator, and then the dithiobenzoate moiety was reduced to thiol group with n-butylamine. Typically, a 25 mL Schlenk flask with a magnetic stir bar was charged with 2.0 g of monomer NIPAM, a certain amount of AIBN and CDB, and 15 mL of redistilled 1,4-dioxane. The reaction system was degassed with nitrogen for half an hour, and then transferred to an oil bath at 70 °C for 48 h. After solvent evaporation, the crude product was dissolved in a small amount of acetone, precipitated in 100 mL of diethyl ether, and separated by filtration. This procedure was repeated twice, and then the light pink product PNIPAMx (x = 1, 2, 3 for the polymer with a mean molecular weight of 10 230, 16 030, or 28 550 and a polydispersity of 1.27, 1.33, or 1.44 determined by GPC, respectively) was obtained after drying at room temperature under vacuum. PNIPAM2. ¹H NMR (300 MHz, D₂O): δ (ppm) 0.98 (–CH(CH₃)₂, 900H), 1.40 (–CH₂–CH–, 300H), 1.82 (–CH₂–CH–, 150H), 3.70 (–CH(CH₃)₂, 150H), 7.1–7.9 (–Ar-H, 10H). FT-IR: 3305, 2972, 2931, 2875, 1650, 1548, 1459, 1384, 1363, 1176, 1130, 693 cm⁻¹. Elemental analysis: C 63.75%, N 12.13%, H 9.73%.

To a solution of PNIPAMx (1.0 g) in 10 mL of redistilled 1,4-dioxane was added 0.01 g of sodium hydrosulfite to prevent oxidation of the thiols to disulfides.⁵¹ The reaction system was degassed with nitrogen for half an hour, followed by the addition of n-butylamine (1.0 mL). The reaction mixture was allowed to stir overnight at room temperature. The collection process of as-synthesized thiol-terminated polymers, denoted as PNIPAM-SHx (x = 1, 2, 3), was the same as that described above for PNIPAMx. PNIPAM-SH2. ¹H NMR (300 MHz, D₂O): δ (ppm) 0.98 (–CH(CH₃)₂, 900H), 1.40 (–CH₂–CH–, 300H), 1.82 (–CH₂–CH–, 150H), 3.70 (–CH(CH₃)₂, 150H), 7.1–7.9 (–Ar-H, 5H). FT-IR: 3305, 2968, 2931, 2876, 1647, 1549, 1463, 1390, 1359, 1168, 1129, 630 cm⁻¹. Elemental analysis: C 63.69%, N 12.21%, H 9.73%.

2.2.3 Synthesis of Pt nanoparticles. In a typical synthesis,⁵² to a stirred solution of 4.0 mL of glycol solution of sodium hydroxide (0.5 M) and 1.0 mL of deionized water at room temperature, 5.0 mL of glycol solution of H₂PtCl₆·6H₂O (19.3 M) was added under nitrogen atmosphere. After 0.5 h, the reaction mixture was allowed to heat to 160 °C and left stirring for 3 h. After that, the dark black solution was cooled to room temperature and transferred into a centrifuge tube. The Pt nanoparticles were obtained when the pH of the mixture was adjusted to lower than 4 with 1.0 M dilute HCl solution. The precipitated Pt nanoparticles were collected by centrifugation, and then dispersed in 25 mL of acetone.

2.2.4 Synthesis of PNIPAM-SH modified Pt nanoparticles. Typically, to a solution of 5.0 mL of above-mentioned Pt dispersion and 5.0 mL of ethanol, 10.0 mL of ethanol solution of a certain amount of PNIPAM-SH was added dropwise. The reaction mixture was stirred in the dark at room temperature for 24 h, and then concentrated by rotary evaporation. The resulting black powder was dispersed in 5.0 mL of methanol and 5.0 mL of deionized water, and the mixture was transferred into a centrifuge tube and kept undisturbed. Then the Pt nanoparticles modified by PNIPAM-SH were collected by centrifugation, dried at room temperature under vacuum for 6 h, and finally dispersed in 10 mL of acetic acid. The corresponding samples were marked as Pt@yPNIPAM-x (x = 1, 2, 3; y = 1.5, 2.5, 3.5), where y represents the initial mass ratio of PNIPAM-SH to Pt.

2.3 General procedure for the enantioselective hydrogenation

Enantioselective hydrogenation reactions were carried out in a 30 mL stainless steel autoclave equipped with a glass liner and a magnetic stirrer. In a typical process, the catalyst Pt@yPNIPAM-x (1.8 × 10⁻³ mmol of total Pt), ethyl pyruvate (0.2 mL, S/C = 1000/1), and cinchonidine (1 mg) in acetic acid (1.3 mL) were charged in the reactor at room temperature. The autoclave was purged with pure hydrogen for several times and then pressurized to the desired hydrogen pressure. The hydrogenation reaction was conducted for a desired period at 25 °C. After the reaction was complete, the catalyst was isolated from the reaction system by adding deionized water (more than 1.0 mL) through phase separation based on the thermosensitivity of PNIPAM-SH polymers, and subsequently used in the next run without further treatment. The liquid phase was extracted with 4.0 mL of diethyl ether, and the organic layer was subjected to GC analysis.

3. Results and discussion

3.1 Catalyst characterization

The particle size and size distribution of Pt nanoparticles were characterized by TEM. Fig. 1 shows the TEM images of representative catalysts Pt@1.5PNIPAM-2 and Pt@2.5PNIPAM-2. It can be clearly observed that the polymer-modified Pt nanoparticles in both catalysts have uniform sizes and are finely dispersed. Statistical analysis was performed by measuring more than 200 Pt nanoparticles on TEM images. The histogram of the particle size distribution showed that the Pt nanoparticles in the two composite catalysts had a very narrow size distribution with an average particle size of about 1.8 nm.

Fig. 1 TEM images of Pt@1.5PNIPAM-2 (a and b) and Pt@2.5PNIPAM-2 (d and e); particle size distributions of Pt@1.5PNIPAM-2 (c) and Pt@2.5PNIPAM-2 (f).

3.2 Catalytic performances

The as-synthesized catalysts Pt@yPNIPAM-x were evaluated in the enantioselective hydrogenation of ethyl pyruvate after chiral modification with cinchonidine. The effects of reaction solvents, modifier concentrations, hydrogen pressure, mean molecular weight and amount of polymer on the catalytic activity and enantioselectivity were investigated systematically.

The effect of various reaction solvents on the conversion and ee value was studied using Pt@2.5PNIPAM-2 as catalyst, and the results are summarized in Table 1. It could be found that the enantioselective hydrogenation of ethyl pyruvate performed in acetic acid led to the best catalytic activity and enantioselectivity as compared with other solvents examined. A high ee of 76% along with 100% conversion was achieved. This may be explained by that the acetic acid-protonated cinchonidine can directly interact with the reactant through an N–H–O type interaction.^12,13 Moderate ee values and above 90% conversions were obtained under the same conditions when various alcohols were selected (Table 1, entries 4, 5 and 7). For comparison, the 1 : 1 ethanol/acetic acid mixture was used. It could be found that the reaction carried out in such a mixed medium gave higher ee (69% vs. 52%) and conversion (99% vs. 94%) compared with the reaction performed in ethanol (Table 1, entries 5 and 6), which suggested the irreplaceable role of acetic acid in the present catalytic system. Inferior catalytic performance was achieved when using water as the solvent because of the insolubility of the chiral modifier in water (Table 1, entry 9). Toluene is widely used in the cinchona alkaloid-modified Pt reaction system,^53,54 but the reaction over Pt@yPNIPAM-x proceeded very slowly in toluene for the catalyst did not disperse well in it.

Table 1 Effect of solvent on the asymmetric hydrogenation of ethyl pyruvate over cinchonidine-modified Pt@2.5PNIPAM-2^a

Entry	Solvent	Conv.^b (%)	ee^b (%)
a Reactions were performed at 25 °C under 4 MPa of hydrogen pressure for 0.5 h with catalyst (total Pt amount) : modifier : substrate molar ratio of 1 : 2 : 1000.b The conversion and ee value were determined by GC with a chiral column, and the absolute configuration of the alcohol product was R.
1	Acetic acid	100	76
2	Acetone	51	37
3	Tetrahydrofuran	81	53
4	2-Propanol	97	42
5	Ethanol	94	52
6	Acetic acid/ethanol (1 : 1)	99	69
7	Methanol	91	53
8	Dichloromethane	12	13
9	Water	62	28

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The amount of chiral modifier is known to have an important influence on the product enantioselectivity in the Pt catalyzed asymmetric hydrogenation of α-ketoesters. As shown in Fig. 2, no ee and poor conversion were achieved as the reaction was carried out without the addition of the chiral modifier. When a small amount of cinchonidine (modifier/Pt molar ratio of 0.5) was employed, both the conversion and ee value increased sharply; for example, a notably enhanced ee of 71% was obtained over the catalyst Pt@2.5PNIPAM-2, along with the conversion raised from 27% to 100%. This proved that the chiral modification of Pt nanocatalysts could not only effectively induce chiral recognition but also significantly enhance hydrogenation rate. This is in accordance with the result reported previously.⁵⁵ A further increase in ee value was observed as the modifier/Pt molar ratio was increased to 1, while the conversion remained unchanged at 100%. Further enhancing the modifier/Pt ratio in the reaction system up to 6, the enantioselectivity and catalytic activity changed only marginally or not at all.

Fig. 2 Dependence of ee value and conversion on the molar ratio of modifier to Pt in the asymmetric hydrogenation of ethyl pyruvate over Pt@yPNIPAM-2. Reaction conditions: S/C 1000/1, 4 MPa H₂ pressure, 25 °C, 0.5 h.

It could be also seen from Fig. 2 that the mass ratio of PNIPAM-SH to Pt in the catalyst had an obvious effect on the enantioselectivity. The catalysts Pt@1.5PNIPAM-2 and Pt@2.5PNIPAM-2 provided relatively higher ee values. When the ratio of polymer to Pt increased to 3.5, decreased ee values were achieved over the catalyst, which may be explained by the steric hindrance effect. According to the mechanistic model for the heterogeneous enantioselective hydrogenation of ethyl pyruvate over cinchona alkaloid-modified Pt catalyst, the chiral modifier is anchored on the Pt surface via the quinoline moiety.⁵⁶ In the present catalysts, the polymer PNIPAM-SH was grafted on the Pt colloid through the strong interaction between the thiol group and unsaturated surface of Pt atoms, therefore the enhancement of polymer amount would result in the decline of the number of surface modification sites available for cinchonidine and thus lead to the relatively low enantioselectivity.

Hydrogen pressure is also an important factor in the enantioselective hydrogenation reaction. The effect of hydrogen pressure on the catalytic performance was studied using Pt@2.5PNIPAM-2 as a model catalyst. In all the cases investigated, the reaction was found to be complete in 0.5 h. While as shown in Table 2, the enantioselectivity of the product markedly depended upon the hydrogen pressure. The ee value increased from 67% to 77% when hydrogen pressure was enhanced from 1 MPa to 4 MPa. A similar behavior was reported in the literature.^37,38,57,58 This phenomenon can be explained by that the increase in the solution hydrogen concentration, as reported by Blackmond et al.,^59,60 is beneficial to the formation of R-(+)-ethyl lactate. A further increase in hydrogen pressure led to no obvious change in ee value, which might be ascribed to the competitive adsorption of substrate, chiral modifier and hydrogen on the metal surface.

Table 2 Effects of hydrogen pressure and mean molecular weight of PNIPAM-SH on the catalytic performance in the asymmetric hydrogenation of ethyl pyruvate^a

Entry	Catalyst	H2 pressure (MPa)	Mn^b	ee^c (%)
a Reaction conditions: S/C/modifier 1000/1/1 25 °C, 0.5 h.b The mean molecular weight of PNIPAM-SH was determined by GPC.c The conversion and ee value were determined by GC.
1	Pt@2.5PNIPAM-2	1	16 020	67
2	Pt@2.5PNIPAM-2	2	16 020	72
3	Pt@2.5PNIPAM-2	3	16 020	74
4	Pt@2.5PNIPAM-2	4	16 020	77
5	Pt@2.5PNIPAM-2	5	16 020	76
6	Pt@2.5PNIPAM-1	4	10 230	77
7	Pt@2.5PNIPAM-3	4	28 550	70

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In order to test the effect of the mean molecular weight of PNIPAM-SH on the catalytic performance of the catalyst system, three PNIPAM-SH samples with different mean molecular weights were synthesized and employed to modify Pt nanoparticles with a same surface modification density of polymer chains. Table 2 summarizes the comparative results of asymmetric hydrogenation of ethyl pyruvate over the as-synthesized catalysts Pt@2.5PNIPAM-x. It could be observed that the two catalysts Pt@2.5PNIPAM-1 and Pt@2.5PNIPAM-2, which were based on the polymer with relatively low molecular weight of 10 230 and 16 030, respectively, exhibited higher enantioselectivity compared to Pt@2.5PNIPAM-3 that was derived from PNIPAM-SH with a high molecular weight of 28 550 (Table 2, entries 4, 6 and 7). This may be explained by that the high-molecular-weight polymer modified Pt nanocatalyst would lead to higher steric hindrance for the subsequent modification of cinchonidine on the surface of Pt nanoparticles.

A kinetic study on catalytic hydrogenation of ethyl pyruvate was performed over three catalysts Pt@yPNIPAM-2 with different amount of polymer. The results are illustrated in Fig. 3.

Fig. 3 The relationship between conversion and reaction time. Reaction conditions: catalyst Pt@yPNIPAM-2, S/C/modifier 1000/1/1, 4 MPa H₂ pressure, 25 °C.

It could be clearly observed that all the three catalysts had very high activity for the asymmetric hydrogenation of ethyl pyruvate. A complete conversion of the substrate was achieved in less than 10 min. Especially for the catalyst Pt@1.5PNIPAM-2, a high conversion of 83% was obtained in 5 min and a high TOF of 17 820 h⁻¹ was achieved. It should be noted that this TOF value is significantly higher than those obtained for chirally modified colloidal Pt catalysts reported in the literature for the asymmetric hydrogenation of ethyl pyruvate (Table 3). Besides the intrinsic properties of colloidal catalysts such as easy accessibility of active sites, the high TOF value obtained in this work may be partially associated with the high hydrophobicity of isopropyl groups in polymer moieties in the catalyst, which would make the catalyst have a higher tendency to adsorb ethyl pyruvate when acetic acid was used as reaction media, and thus would lead to the enrichment of reactants on the catalyst. Compared with Pt@1.5PNIPAM-2, a slight decrease in the reaction rate was observed over Pt@2.5PNIPAM-2 and Pt@3.5PNIPAM-2, and somewhat lower conversions of 72% and 69%, respectively, were attained in 5 min. Accordingly, relatively low TOF values of 14 700 h⁻¹ and 12 870 h⁻¹ were obtained over Pt@2.5PNIPAM-2 and Pt@3.5PNIPAM-2, respectively. The decrease in catalytic activity may be attributed mainly to the enhanced steric hindrance for cinchonidine modification and subsequent relative inaccessibility of active sites by substrate molecules resulted from the increase of polymer amount on the colloidal Pt surface. It is desirable to point out that the TOF values achieved over the latter two catalysts were also at high levels compared to other colloidal Pt catalyst systems reported previously (Table 3). It is thus logical to deduce that PNIPAM-modification provides an efficient approach for Pt nanocatalysts with enhanced catalytic activity in asymmetric hydrogenation of α-ketoesters, and that the amount of polymer plays an important role on the catalytic activity.

Table 3 Comparison of colloidal Pt catalyst systems in asymmetric hydrogenation of ethyl pyruvate

Catalyst	Stabilizer	H2 pressure (MPa)	TOF^a (h^−1)	ee (%)	Ref.
a TOF is defined as the moles of substrate reacted per mole of Pt (total Pt in the catalyst) per hour.
Pt–DHCin	Dihydrocinchonidine	0.1	3960	78	34
Pt–PVP	Polyvinylpyrrolidone	4	396	92	35
Pt–MMK	Acetone	7	15 110	36	36
Pt–HEA16Cl	Surfactant	4	1860	55	37
Pt@hPGx–Cn–mPEGy	Dendritic core-multishell architectures	7	5170	73	38
Pt@yPNIPAM-x	PNIPAM-SH	4	17 820	80	This work

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3.3 Catalyst recycling and stability

PNIPAM-SH polymers show a thermosensitive behavior in water with a LCST at about 32 °C. That is, PNIPAM-SH polymers are well soluble in water at room temperature. In addition, PNIPAM-SH polymers are also well soluble in acetic acid (Fig. 4a), in which no thermosensitivity was observed for these polymers. However, a phase separation was observed to occur simultaneously when water was added into the solution of PNIPAM-SH in acetic acid at room temperature (Fig. 4b). For both water and acetic acid are good solvents for PNIPAM-SH polymers, the phase separation of PNIPAM-SH in water/acetic acid mixed solvent at room temperature can be due to the depressed LCST of PNIPAM-SH in this mixed solvent. This phase separation is different from those generally applied to precipitate the soluble polymers by using a kind of poor solvent. The phenomenon that the LCST of PNIPAM polymers depressed in water/organic solvent mixture was also reported in the literature.^47,48 It was stated that the PNIPAM solution in water/methanol mixture showed a decreased LCST of −7.5 °C. In order to verify the thermosensitivity of PNIPAM-SH in water/acetic acid mixed solvent, we continuously lowered the temperature of PNIPAM-SH solution in water/acetic acid mixture. It was observed that the turbid solution became completely clear at −15 °C (Fig. 4c). This demonstrated that PNIPAM-SH has thermosensitivity in the water/acetic acid mixed solvent with a LCST far below room temperature. Similar phase separation behavior was observed for the catalyst Pt@yPNIPAM-x (Fig. 4d and e). Thus after each hydrogenation reaction, the catalyst could be easily separated from the reaction system by adding deionized water at room temperature based on the thermosensitivity of polymers, and then well redispersed in acetic acid for next cycle (Fig. 4f).

Fig. 4 Photographs of PNIPAM-SH2 in acetic acid (a), in a water/acetic acid mixture at 25 °C (b) and in a water/acetic acid mixture at −15 °C (c). Photographs of Pt@2.5PNIPAM-2 in acetic acid (d), in a water/acetic acid mixture at 25 °C (e) and redispersed in acetic acid (f).

To assess the stability and reusability of the colloidal Pt catalysts during the asymmetric hydrogenation of ethyl pyruvate, recycling experiments were carried out over Pt@2.5PNIPAM-2 and Pt@1.5PNIPAM-2. As shown in Fig. 5A, the catalyst Pt@2.5PNIPAM-2 exhibited notably high stability and durability for the hydrogenation reaction, and no obvious decrease in catalytic activity and enantioselectivity was observed for eleven runs. Especially, complete conversion of ethyl pyruvate was achieved in the first ten consecutive runs, along with the ee value remained stable around 77%. Apart from this, a slight increase in the ee value could be observed from 77% in the first run to 80% in the third run, which may be due to the clearer surface of Pt nanoparticles after being treated repeatedly with acetic acid/water mixtures during the recycling experiments. It could be observed from Fig. 5B that the catalyst Pt@1.5PNIPAM-2 was also highly stable and reusable for the asymmetric hydrogenation of ethyl pyruvate. The catalytic activity and enantioselectivity showed no obvious decrease for at least eleven runs. To the best of our knowledge, this is the best result in terms of reusability for the chirally modified colloidal Pt catalysts.^34–39 The excellent stability and durability of the present catalysts could be due to the good thermosensitivity of the polymer as well as the strong interaction between the thiol group of the stabilizer and unsaturated surface of Pt nanoparticles. In addition, it should be once again highlighted that the recycling process of catalyst is rather simple and practical. The satisfactory results obtained in this work indicated that thermosensitive polymer modifying of Pt nanoparticles represents an efficient and promising strategy to improve the stability and reusability of colloidal Pt catalysts.

Fig. 5 Recycle studies of Pt@2.5PNIPAM-2 (A) and Pt@1.5PNIPAM-2 (B) in the asymmetric hydrogenation of ethyl pyruvate. Reaction conditions: S/C/modifier 1000/1/1, H₂ pressure of 4 MPa, 25 °C, 15 min.

In attempt to get further insight into the stability of these Pt catalysts during the recycling process, Pt@1.5PNIPAM-2 and Pt@2.5PNIPAM-2 after five and eleven cycles were submitted to TEM characterization. As shown in Fig. 6c and f, a slight increase in particle size to 2.0 ± 0.3 nm and 1.9 ± 0.4 nm could be observed for Pt@1.5PNIPAM-2 and Pt@2.5PNIPAM-2 after eleven cycles, respectively. This suggested that the Pt nanoparticles were stable during the recycling process. However, aggregation was observed to take place for the used catalysts. It could be found that the individual nanoparticles in the original catalysts gradually form small aggregates including several particles after the 5^th run (Fig. 6a and d) and large aggregates including dozens of particles after the 11^th run (Fig. 6b and e). This aggregation could be attributed to the formation of polymer aggregates, in which the embedded Pt nanoparticles was not obviously enlarged. This indicated that the polymer can effectively stabilize the Pt nanoparticles. This phenomenon was in agreement with those observed for the Pt nanoparticles stabilized by surfactant³⁷ or dendritic core–multishell architectures.³⁸

Fig. 6 TEM images of Pt@1.5PNIPAM-2 after five (a) and eleven (b) cycles, and Pt@2.5PNIPAM-2 after five (d) and eleven (e) cycles; particle size distributions of Pt@1.5PNIPAM-2 (c) and Pt@2.5PNIPAM-2 (f) after eleven cycles.

The Pt leachings during the recycling experiments over the two catalysts were tested. After each cycle, the supernatant was separated from the catalyst precipitate by decantation and combined together. ICP-AES analysis showed the total Pt leaching for eleven runs was only 0.6% and 2.1% for Pt@2.5PNIPAM-2 and Pt@1.5PNIPAM-2, respectively. This indicated that the colloidal Pt catalysts modified by PNIPAM-SH were highly stable during the asymmetric hydrogenation reactions and could be well recovered from the catalytic system. Comparing the two catalysts, it could be also concluded that the increase of polymer amount was beneficial to the improvement of catalyst stability.

4. Conclusions

The colloidal Pt catalysts were stabilized by thermosensitive polymer PNIPAM-SH and applied for the first time in the asymmetric hydrogenation of ethyl pyruvate in the presence of cinchonidine. Notably high catalytic activity and enantioselectivity were achieved over these catalysts, which were represented by TOF of 17 820 h⁻¹ and ee of 80%, respectively. The high catalytic performance could be attributed to the high hydrophobicity of isopropyl groups in polymer moieties and the easy accessibility of active centers for metal colloidal catalyst. Moreover, these colloidal Pt catalysts were very stable in the reaction system and could be easily recovered for reuse based on the thermosensitivity of PNIPAM-SH. After eleven cycles, both the catalytic activity and enantioselectivity were well maintained. To the best of our knowledge, the catalytic activity and reusability achieved in the present work over PNIPAM-modified Pt nanocatalysts were the best ones among those obtained over colloidal Pt catalysts. These inspiring results indicated that the stabilization of Pt nanoparticles with thermosensitive polymer was an efficient and promising strategy to develop a kind of asymmetric hydrogenation nanocatalysts with high catalytic performance and excellent reusability.

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant No. 21203102), the Tianjin Municipal Natural Science Foundation (Grant No. 14JCQNJC06000), MOE (IRT13R30) and 111 Project (B12015).

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