Polymer-Bound Chiral Gold-Based Complexes as Efficient

Letter pubs.acs.org/acscatalysis

Polymer-Bound Chiral Gold-Based Complexes as Efficient Heterogeneous Catalysts for Enantioselectivity Tunable Cycloaddition Mingjin Chen, Zhan-Ming Zhang, Zhunzhun Yu, Haile Qiu, Ben Ma, Hai-Hong Wu,* and Junliang Zhang* Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, P. R. China S Supporting Information *

ABSTRACT: The polymer-bound Ming-Phos was easily prepared by the highly efficient immobilization of our recently developed Ming-Phos in polystyrene by copolymerization in the presence of 5% DVB, which shows good performance in the application of heterogeneously catalyzed asymmetric cycloaddition. A pair of enantiomers of the product with opposite configurations could be easily delivered in high yields with excellent enantioselectivity by the application of two diastereomers of the heterogeneous catalyst. This heterogeneous catalyst not only exhibits similar catalytic activity and enantioselectivity to those of the homogeneous catalyst but also could be easily recovered and recycled for up to eight cycles. KEYWORDS: gold, heterogeneous catalysis, enantioselectivity, cycloaddition, reuse

T

catalysis,8 we wondered whether this new type of chiral ligand can be immobilized on a suitable polymer or not and what the difference in the catalytic performance between the resulting chiral polymer-supported gold catalyst and the corresponding homogeneous gold catalyst would be. Herein, we wish to report our efforts in the synthesis of polystyrene-bound chiral MingPhos/gold complexes and their application for asymmetric cycloaddition. These catalyst systems not only allow easy catalyst separation from the product mixture for eight cycles but also remain similar in enantioselectivity to the homogeneous catalyst. Moreover, a pair of diastereomeric polymersupported complexes can regulate the chirality. After retrosynthesis analysis, we envisaged the following strategy to immobilize Ming-Phos to polymer (Scheme 1): the introduction of a vinyl group on the aryl ring of Ming-Phos delivers the vinyl substituted monomer, followed by copolymerization with styrene and 1,4-divinylbenzene.9 This strategy has several advantages such as the easy synthesis of a pair of two diastereomers without changing the catalytic activity related electronic properties of phosphine. However, this strategy may also face several problems and challenges including the following: (1) a small modification of the R substituent on the aryl ring of the Ming-Phos often led to a significant variation in enantioinduction (ee from 73% to 94%). Thus, the introduction of a vinyl group onto the aryl ring (such

he immobilization of chiral catalysts for asymmetric reactions is one of the most promising solutions to the problems associated with difficulties in the recovery and reuse of expensive homogeneous catalysts and product contamination.1 Over the past two decades, the studies of polymersupported catalysts, especially chiral ones, have attracted a great deal of interest in retaining the high selectivity and activity of homogeneous catalysts and facilitating catalyst/product separation as well as catalyst recycling.2 However, the immobilization of a new type of chiral ligand/catalyst that promotes transformations with an efficiency and enantioselectivity that are similar (or higher) to those of the related homogeneous complexes is highly desirable.3 Homogeneous gold(I) complexes have shown their unrivalled power toward a variety of carbon−carbon and carbon− heteroatom bond-forming reactions with high efficiency and selectivity.4 However, only a handful of polymer-supported gold(I) catalysts for heterogeneous catalysis have been developed thus far.5 For example, Akai and co-workers reported several elegant insoluble polystyrene-bound triphenylphosphine-gold(I) complex-catalyzed reactions.5 Recently, Yu and co-workers made a polystyrene-supported benzotriazole-gold(I) complex and applied it for three documented transformations.6 Because the development of enantioselective homogeneous gold catalysis still poses a considerable challenge,7 it is not surprising that chiral polymer-supported gold catalysts have not yet been explored thus far. Inspired by the ease of preparation and good performance of our recent developed Ming-Phos in asymmetric homogeneous gold© 2015 American Chemical Society

Received: September 4, 2015 Revised: November 11, 2015 Published: November 17, 2015 7488

DOI: 10.1021/acscatal.5b01963 ACS Catal. 2015, 5, 7488−7492

Letter

ACS Catalysis Scheme 1. Strategy for the Immobilization of Ming-Phos

Scheme 3. Preparation of Polymers and Polymer-Bound Gold(I) Catalysts

Scheme 2. Preparation of the Chiral Monomers Table 2. Study of the Effect of the Polymer Support on the Efficiency and Enantioselectivitya

Table 1. Polymerization of the Model Substrate

entry

reaction time (h)a

oxidized P (%)b

1 2 3 4

2 6 8 12

o 5% 20% 42%

a c

a

The sample from four parallel experiments. bThe percentage that was oxidized, oxidized P/overall P.

entry

catalyst (5 mol %)

time (h)

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13

(S,Rs)-L1AuNTf2 C0 C1 C2 C3 C4 AgCl (R,Rs)-L1AuNTf2 C5 (S,Rs)-L2AuNTf2 C6 (R,Rs)-L2AuNTf2 C7

0.5 3 3 3.5 4.5 6 14 0.5 3 0.5 3 0.5 5

93 90 92 90 80 65 4 91 85 91 92 88 84

All reactions were carried out under nitrogen. Determined by chiral HPLC.

3a, eec (%) 3a, 96 3a, 93 3a, 95 3a, 75 3a, 65 3a, 50 3a, 0 ent-3a, ent-3a, 3a, 86 3a, 77 ent-3a, ent-3a,

b

95 95

76 50

Isolated yield.

synthesized in 60−86% yields on a large scale according to our previous procedure8 from the readily available Ellman ligand12 and the corresponding organometallic reagents (Scheme 2). With these monomers in hand, we next turned to the immobilization of them in a polymer by copolymerization. Due to steric effects of ligands, we tried to copolymerize the monomers at different temperature for 24 h. The yield at 85 °C (65.3%) was higher than at 70 °C (30.5%). However, it was found that the phosphine was oxidized under these conditions (by 31P NMR, the peak from −18.9 to 32.7). To find the optimal reaction conditions for the copolymerization and prevent oxidation of the phosphine, a simple diphenyl(4vinylphenyl)phosphine was used as the model monomer to screen the reaction conditions for the copolymerization (Table 1). After several attempts, we were pleased to find that the phosphine was oxidized less than 5% when the reaction was run in a sealed tube within 6 h.

as 4-vinylphenyl or 4-vinylnaphthyl) may lead to a reduction in the enantioselectivity. (2) During the copolymerization, the phosphine may be oxidized to phosphine oxide and lose its activity.10 (3) The effect of the polymer-supported catalyst on the efficiency and enantioselectivity must be considered. In contrast to the grafting of functionalized ligands, copolymerization of functionalized ligands has some advantages such as its ease of synthesis and rich content of ligands;3,11 however, it often results in catalysts with a lower enantioselectivity and efficiency than its homogeneous catalyst. Even with these potential problems and challenges, we still decided to attempt to immobilize Ming-Phos to the polymer and study its catalytic performance in heterogeneous gold asymmetric catalysis. Our initial study starts from the synthesis of two pairs of diastereomeric chiral ligands L1−L2, which could be easily 7489

DOI: 10.1021/acscatal.5b01963 ACS Catal. 2015, 5, 7488−7492

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ACS Catalysis Scheme 4. Reaction Scopea

Figure 1. Reaction conversion versus reaction time with the use of C1 catalyst.

Figure 2. Plot of the conversion and ee versus the number of times recycled.

Figure 3. TEM images of (a) heterogeneous catalyst C1; and (b) C1 after it was run eight times.

a

With this information in mind, several soluble and insoluble polymers P0−P4 were synthesized through copolymerization of (S,Rs)-L1 with styrene in the presence of different proportions of DVB (Scheme 3). The polymers P0−P4 were thoroughly washed until there was no monomer contamination (determined by TLC). The polymers were then treated with (Me2S)AuCl in DCM at room temperature for 10 h. Hexanes were added to completely precipitate the polymer-bound gold− chloride complex. Subsequent treatment of the gold−chloride complex with the silver salt AgNTf2 in DCE for 30 min could generate the corresponding cationic polymer-bound gold

catalysts in situ. As the results illustrated in Table 2, the reaction efficiency and enantioselectivity decrease as the degree of the cross-linking was increased (Table 2, entries 2−6).13 It should be noted that AgCl itself cannot efficiently catalyze the cycloaddition (Table 2, entry 7). Catalysts C1 and C0 derived from 5% DVB and non-DVB, respectively, produce similar levels of reactivity to that of the homogeneous catalyst (Table 2, entries 1−3). For example, in the presence of 5 mol % polymer-bound catalyst Co and C1, the reaction proceeded smoothly to give 3a with 93% ee in 90% and 91% yields, respectively. However, the non-cross-linking catalyst Co could 7490

The diastereomeric ratios were >20:1 for all the reactions.

DOI: 10.1021/acscatal.5b01963 ACS Catal. 2015, 5, 7488−7492

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ACS Catalysis

substituents were examined, and the corresponding optically active products ent-3a−d were obtained in 74−88% yields as single diastereomers with excellent enantioselectivity (90−96% ee). Then, the scope of alkyl-substituted 2-(1-alkynyl)-2-alken1-ones 1 was investigated, and the corresponding products ent3e-g were isolated in 81−87% yields with good enantioselectivity, which further emphasizes the general substrate scope of this enantioselective transformation. We then turned to study the reaction scope by the use of C1 as the chiral polymerbound gold catalyst. To our delight, all of the reactions of a broad range of 2-(1-alkynyl)-2-alken-1-ones with various nitrones could also furnish the desired enantioenriched products 3b−g in high yields as a single diastereomer with 94−99% ee. In summary, we have developed an efficient method for the synthesis of a polymer-supported gold catalyst. The chiral ligand can easily copolymerize with styrene with a low concentration of cross-linking. Compared with homogeneous catalysts, the polymer-bound gold catalysts exhibited the same catalytic activity toward various substrates, and they showed excellent diastereo- and enantioselectivity. A pair of diastereomeric catalysts delivered two enantiomers in good yields with good selectivity. Moreover, this polymer-bound gold catalyst can achieve eight catalytic cycles without the loss of enantioselectivity, and it is applicable to large-scale synthesis. Further studies including the extension of the polymer-bound ligand to other gold-catalyzed reactions and other transitionmetal asymmetric catalysts are underway in this laboratory.

be recovered in only an 85% yield; meanwhile, 5% DVB derived C1 could be recovered in more than a 97% yield. Based on these results, we chose 5% cross-linking (DVB) and 85 °C as the optimal conditions to synthesize the other three polymers P5-P7 and polymer-bound catalysts C5-C7 from the corresponding (S,Rs)-L1, (R,Rs)-L2 and (S,Rs)-L2. Gratifyingly, the (S, Rs)-L1-derived polymer-bound gold catalyst C5 could also give a similar efficiency and enantioselectivity to that of the homogeneous gold catalyst (S,Rs)-L1AuNTf2 (Table 2, entries 8 and 9). More importantly, identical to the outcome of the homogeneous catalysis, the diastereomeric C1 and C5 delivered enantioenriched product with the opposite absolute stereochemistry (Table 2, entries 3 and 9). In comparison, polymer-bound gold catalysts C6 and C7 give similar efficiencies but low enantioselectivities compared to those of homogeneous gold catalysts derived from the pair of diastereomers L2 (Table 2, entries 10−13). Having established the good catalytic performance of polymer-bound gold catalysts C1 and C5 in the cycloaddition reaction with tunable enantioselectivity, we next examined the possibility of recyclability. After the reaction, the polymer catalyst was partially dissolved in DCE and difficult to recover by filtration.14 The addition of methanol to the mixture could recover 98% of the catalyst, but unfortunately, the catalyst loses its activity in the second run. We initially used methanol to recover the polymer catalyst, but the recovered catalyst loses its activity. Diethyl ether was then used as the solvent for the recovery of catalyst, and the recovered catalyst loses its catalytic activity after three cycles.15 Finally, we were pleased to find that n-hexanes could nicely precipitate the polymer, and the catalyst C5 can be easily recovered in almost a quantitative yield through simple filtration. More importantly, this polymerbound gold catalyst could be recycled five times with similar enantioselectivity, albeit a longer reaction time is required (Table S2, please see the details in SI). Kinetics experiments were then carried out to investigate the catalyst deactivation.16 It was found that catalyst activation decreased gradually as the number of times recycled increased (Figures 1 and 2). We envisaged that the weakly coordinated counterion Tf2N− of the gold catalyst may be gradually replaced by the Cl− during the recovery process,17 and the resulting Phos-Au(I)-Cl has no catalytic activity, thus causing the catalyst deactivation. With this hypothesis in mind, we succeeded in reactivating the catalyst by the addition of the silver salt AgNTf, and three more cycles could be run. In detail, the yield was higher than the fifth run, and the reaction time was obviously shortened from 36 to 6 h. In the eighth run, the yield dropped to 72%, but the enantioselectivity still remained at an excellent level. It should noted that the catalyst loading of the eighth catalyst was 85% of the initial catalyst C1. By TEM analysis (Figure 3), we did not find the formation of gold nanoparticles. Inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis revealed the leaching of the gold complex dropped slowly from 1.5% to 1.0% for the first three cycles, which may be caused by the microencapsulated effect,18 after which the leaching of the gold complex remained at 0.8%. A large scale (3 mmol) reaction was investigated, delivering 1.05 g of product 4a in an 82% yield, with a 94% ee at 2.5 mol % catalyst, which indicated that the polymer method may be practically useful in organic synthesis. The versatility of the polymer-supported catalyst C5 toward the asymmetric cycloaddition of various substrates was further investigated (Scheme 4). Various nitrones with different

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscatal.5b01963. Experimental procedures and characterization data of the ligands as well as copies of the 1H and 13spectra and the HPLC spectra (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support from the National Natural Science Foundation of China (21425205, 21372084) and the Shanghai Eastern Scholar Program are appreciated. We are grateful to Aiqing Zhong and Jianhua Wu in ECNU for the GPC and Guirong Zhang for the inductively coupled optical emission spectroscopy (ICP-OES) analysis.

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REFERENCES

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DOI: 10.1021/acscatal.5b01963 ACS Catal. 2015, 5, 7488−7492