Synthesis of MacMillan catalyst modified with ionic liquid as a recoverable catalyst for asymmetric Diels–Alder reaction

Abstract

MacMillan catalyst was modified with imidazolium ionic liquid by ester linkage and acts as recoverable and reusable catalyst for asymmetric Diels–Alder reactions. A Diels–Alder reaction between cyclopentadiene and crotonaldehyde was carried out using MacMillan catalyst modified with ionic liquid (5 mol%) using trifluoroacetic acid (5 mol%) as co-catalyst in acetonitrile–water (95 : 5) at room temperature, to give 94% conversion of Diels–Alder adduct with exo/endo (1 : 1.1) and 90% ee of endo product. The catalyst was recovered and reused up to 5 cycles with a slight decrease in ee and product conversion.

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Introduction

The Diels–Alder reaction is an important tool for the synthesis of enantiomerically enriched cyclohexene moieties and also for carbon–carbon bond formation reactions. It is a key step for the synthesis of many natural products and pharmaceutical compounds.^1–4 An enantioselective Diels–Alder reaction was used for the synthesis of (−)-oseltamivir by Fukuyama and co-workers.^5,6 The first enantioselective Diels–Alder reaction was reported by MacMillan and co-workers, involving an organocatalyst, which proceeds by a LUMO-lowering activation mechanism.^7–9 Several organocatalysts employed in the enantioselective Diels–Alder reaction are chiral diamines,^10–12 hydrazides,^13–19 and diarylprolinol ethers.^20,21

Organocatalysts used in this reaction have some limitations, such as requiring high catalyst loading or long reaction times, and also they are not easily separated from the reaction mixture and are therefore difficult to recover and recycle. Several research groups have made successful attempts to overcome these problems by immobilizing or attaching the catalytic unit on recyclable supports. Tyrosine-derived imidazolidin-4-one was immobilized on supports through covalent bonds on modified polyethylene glycol,²² poly(methylhydrosiloxane) (PHMS),²³ siliceous and polymer-coated mesocellular foam (MCF),²⁴ mesoporous organosilica sphere,²⁵ and chiral organosilica polymer.²⁶ Liang et al. reported, use of internal functionalities of the dendrimer to attach imidazolidinone as guests to the interior of the dendrimer using olefin metathesis.²⁷ Pecinovsky et al. developed a nanoporous heterogeneous chiral catalyst via acid-induced liquid crystal self-assembly and subsequent photopolymerization of the monomer in the imidazolidinone unit.²⁸ Selkälä et al. immobilized MacMillan catalyst on JandaJel™ through amide bond using JandaJel-NH₂ and N-Fmoc-protected (S)-phenylalanine.²⁹ Haraguchi et al. used polymer supported sulphonic acid for immobilization of MacMillan catalyst by ionic interaction via ion exchange between sulfonated polymer and quaternary ammonium salt.³⁰ They also developed main chain polymer by the reaction of chiral imidazolidinone dimer with disulfonic acid.³¹ Mitsudome et al. also supported MacMillan catalyst on montmorillonite clay using a cation exchange method.³² Fluorous tag and tetraarylphosphonium with MacMillan catalyst can act as a recoverable catalyst.^33,34 Room temperature ionic liquids were also used for recovery of MacMillan catalyst.³⁵ Imidazolium based ionic liquids connected with MacMillan catalyst through covalent bonds and supported on silica were also used for this reaction.^36,37 In our ongoing research project on the development of recoverable catalysts, recently we developed α,α-diphenyl-(L)-prolinol modified with imidazolium ionic liquid as recoverable catalyst for asymmetric reduction of ketones.³⁸ Herein, we wish to report the synthesis of MacMillan catalyst modified with imidazolium ionic liquid as a recoverable catalyst for enantioselective Diels–Alder reaction.

Results and discussion

Preparation of modified McMillan catalyst modified with ionic liquid

MacMillan catalyst, and the catalyst modified with imidazolium cation, and bromide, tetrafluoroborate and hexafluorophosphate as counter anion (6–8) are shown in Fig. 1. Precursors 1–4 were synthesized according to procedures reported by Kristense et al.³⁹ Bromoester 5 was synthesized by using a 5-bromopentanoyl chloride and compound 4 in the presence of methanesulfonic acid at r.t., in 70% yield. The bromoester 5 was treated with 1-methylimidazole at 100 °C for 20 min, to give MacMillan catalyst @ imidazolium bromide (6) in 91% yield. The counter anion bromide of the ionic liquid (6) was exchanged by KBF₄ and KPF₆ in acetone and water, which afforded the tetrafluoroborate (BF₄) and hexafluoroborate (PF₆) anion containing ionic liquids in 75% and 81% yield, respectively (Scheme 1).

Fig. 1 MacMillan’s catalyst and ionic liquid modified MacMillan catalysts.

Scheme 1 (a) SOCl₂, methanol, r.t., 28 h, 97% (b) ethanolamine, r.t., 26 h, 84% (c) acetone, i-PrOH, p-TSA, reflux, 5 h, 81% (d) CH₃SO₃H, 5-bromovalleric acyl chloride, 0–5 °C, 3.5 h, 70% (e) 1-methylimidazole, 100 °C, 10 min, 91% (f) KBF₄, H₂O–acetone, r.t., overnight, 75% (g) KPF₆, acetone–H₂O, r.t., overnight, 82%.

Optimization of reaction conditions for Diel–Alder reaction

Ionic liquid supported MacMillan catalysts (6–8) were used for Diels–Alder reactions, choosing crotonaldehyde (9) and cyclopentadiene (10) as model substrates. Initially, we screened different solvents for the Diels–Alder reaction using IL 6 (10 mol%) and trifluoroacetic acid (10 mol%) as co-catalyst (Table 1). Acetonitrile as a solvent was found to be better than other solvents (water and methanol), and gave 74% conversion of Diels–Alder adduct with exo/endo (1 : 1) and 75% ee of endo product (12). In methanol we obtained 12% of desired product (11 and 12) and 88% of its dimethyl acetal was formed as a by-product (Table 1, entry 5). Non-polar solvents like dichloromethane also gave comparable ee of endo product, but conversion of product was poor compared to acetonitrile (Table 1, entry 6). We have also screened IL 7 and 8 in acetonitrile, and IL 8 gave better ee of endo product (12) compared to other ILs (Table 1, entries 7 and 8). The effect of water was studied for the reaction and it was found that 5% water in acetonitrile improved the ee and ratio of endo product (Table 1, entry 9). A catalyst loading of 2 mol% was sufficient to convert to product, but better ee (90%) was obtained with 5 mol% (Table 1, entries 10 and 11). We have also isolated the product by column chromatography in 84% isolated yield. We further increased the amounts of water up to 10% in acetonitrile and ee was retained but conversion dropped to 80% (Table 1, entry 12).

Table 1 Screening of different solvents and ionic liquids as a catalysts for Diels–Alder reaction^a

Entry	Catalyst	Solvents	Conversion^b (%)	(exo/endo)^c	ee (endo)^d
a IL 6–8 (2–10 mol%) was dissolved in solvent (1 mL), trifluoroacetic acid (2–10 mol%), crotonaldehyde (0.5 mmol, 42 μL) and cyclopentadiene (0.5 mmol, 41 μL) was added and stirred at room temperature.b Conversion to product was determined by gas chromatography.c exo/endo ratio was determined by gas chromatography.d ee was determined by gas chromatography using β-Dex chiral column.e 88% dimethyl acetal of desired product was formed as a by-product.f Catalyst 8 (2 mol%) was used.g Catalyst 8 (5 mol%) was used.h 84% isolated yield was obtained after purification by column chromatography.
1	6	Acetonitrile	73	1.0 : 1.0	75
2	6	THF	—	—	—
4	6	Water	44	1.0 : 1.4	45
5	6	MeOH	12^e	1.3 : 0.7	53
6	6	CH2Cl2	42	1.1 : 1.0	70
7	7	Acetonitrile	81	1.1 : 0.9	83
8	8	Acetonitrile	76	1.0 : 1.0	85
9	8	Acetonitrile–water (95 : 5)	88	1.0 : 1.2	88
10	8	Acetonitrile–water (95 : 5)	82	1.0 : 1.2	85^f
11	8	Acetonitrile–water (95 : 5)	94	1.0 : 1.1	90^g^,^h
12	8	Acetonitrile–water (90 : 10)	80	1.0 : 1.1	90^g

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Effect of different co-catalysts on the Diels–Alder reaction

The effects of different acids as co-catalysts were investigated for the Diels–Alder reaction between crotonaldehyde and cyclopentadiene using IL 8 as a catalyst (Table 2). Trifluoroacetic acid (TFA) was found to be a better choice of co-catalyst in terms of conversion and ee of endo product compared to the other co-catalysts like HCl, H₂SO₄, acetic acid, HClO₄ and p-TSA. In the case of HClO₄ and acetic acid the ratio of endo product (12) was improved, but the conversion and ee of endo product (12) were poor compared to TFA.

Table 2 Screening of different co-catalysts for the Diels–Alder reaction catalysed by IL 8^a

Entry	Co-catalyst	Conversion^b (%)	(exo/endo)^c	ee^d (%)
a IL 8 (5 mol%) was dissolved in CH3CN–water (9 : 55, 1 mL), co-catalyst (5 mol%), crotonaldehyde (0.5 mmol, 42 μL) and cyclopentadiene (0.5 mmol, 41 μL) was added and stirred at room temperature.b Conversion was determined by gas chromatography.c exo/endo ratio was determined by gas chromatography.d ee was determined by gas chromatography using β-Dex chiral column.
1	HCl	30	1 : 1.1	76
2	H2SO4	26	1 : 1.1	40
3	CH3COOH	11	1 : 1.4	70
4	Trifluoroacetic acid	94	1 : 1.1	90
5	HClO4	26	1 : 1.4	55
6	p-TSA	61	1 : 1.2	82
7	—	2	1 : 1.3	44

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Comparisons of recoverable MacMillan catalysts

We have compared the results of IL 8 with other reported recoverable MacMillan catalysts for enantioselective Diels–Alder reaction between crotonaldehyde and cyclopentadiene (Table 3). The results show that IL 8 was found to be better than other reported catalysts in terms of lower catalyst loading (5 mol%), shorter reaction times and comparable ee of endo Diels–Alder product (12) (Table 3).

Table 3 Comparisons of recoverable reported MacMillan catalysts with IL 8 for enantioselective Diels–Alder reaction between crotonaldehyde and cyclopentadiene

Entry	Recoverable MacMillan catalyst	Catalyst loading (mol%), reaction time (h)	Yield (%) (exo/endo)	ee (endo) (%)	Ref.
1	Immobilized on JandaJel™	10, 24	91 (1 : 1.2)	91	29
2	Nanoporous heterogeneous	10, 24	71 (1 : 1.3)	90	28
3	Fluorous organocatalyst	10, 40	80 (1 : 0.9)	92	33
4	Montmorillonite clay	0.1 g, 48	85 (1 : 1.7)	89	32
5	Polymer supported via ion exchange	10, 24	99 (1 : 0.8)	83	30
6	Supported ionic liquid catalyst	10, 22	61 (1 : 1)	83	36, 37
7	Tetraarylphosphonium supported	10, 12	95 (1 : 1.4)	92	34
8	IL-8	5, 2	94 (1 : 1.1)	90	This paper

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Table 4 Substrates scope for Diels–Alder reaction using IL 8^a

Entry	Substrate	exo/endo^b	Yield^c (%)	ee^d (%) (exo/endo)
a IL 8 (5 mol%) was dissolved in CH3CN–water (95 : 5, 1 mL), trifluoroacetic acid (5 mol%), cinnamaldehyde or its derivatives (0.5 mmol) and cyclopentadiene (0.5 mmol) was added and stirred at room temperature.b Calculated by ^1H NMR.c Isolated yield after purification by column chromatography.d ee was determined by HPLC using Chiralcel OD-H column after reduction to alcohol.
1	13a	1.2 : 1	92	82 : 78
2	13b	1.2 : 1	84	75 : 76
3	13c	1.1 : 1	87	80 : 82
4	13d	1.1 : 1	61	75 : nd

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Substrate scope for Diels–Alder reaction

After optimization of the reaction conditions for the Diels–Alder reaction, in order to generalize the substrate scope we carried out the Diels–Alder reaction between cyclopentadiene and cinamaldehyde derivatives (13a–d) using IL 8 (5 mol%) and TFA (5 mol%) in acetonitrile–water (95 : 5) at room temperature for 24 h. Cinnamaldehyde gave 92% yield of the corresponding Diels–Alder adduct with exo/endo (1.2 : 1) and ee for 14a/15a (82 : 78) (Table 4, entry 1). An electron-withdrawing group (nitro) at the p-position on cinnamaldehyde (13b) gave a comparable yield and the ee of exo product (14a) dropped (entry 2). An electron-donating group (methoxy) on the p-position of cinnamaldehyde (13d) was found to be less reactive compared to cinnamaldehyde and p-nitrocinnamaldehyde (entry 4). p-Chloro-cinnamaldehyde (13c) did not show a significant difference in reactivity and enantioselectivity compared to cinnamaldehyde (entries 1 and 3).

Recovery and reusability of the IL 8

The recycling of MacMillan catalyst modified with imidazolium ionic liquid 8 was successfully achieved for the enantioselective Diels–Alder reaction between cyclopentadiene (9) and crotonaldehyde (10) (Table 5). IL 8 was recovered and reused for up to 5 cycles with minor loss of conversions of Diels–Alder adducts and 90–86% ee’s of endo product (12), but exo/endo ratios were retained. After each fresh catalytic cycle, the reaction mixture was passed through a pad of anhydrous sodium sulfate to remove the water from the reaction. The solvent was removed under vacuum and hexane–diethyl ether (5 mL, 1 : 1) was added. Subsequently IL 8 becomes a viscous liquid and the product was in solution, which was decanted off. The ¹H and ¹⁹F NMR and HRMS data of recovered catalyst and fresh catalyst are in agreement (ESI, Fig. 4 and 6†). We have treated IL 8 with 1 equivalent of trifluoroacetic acid in acetonitrile–water (95 : 5), recorded the ¹H NMR and the peak at 2.3 ppm of OCH₂CO of the ester linker indicates that the ester is not hydrolyzed during the reaction (ESI, Fig. 5†).

Table 5 Recycling performance of IL 8 for Diels–Alder reaction between crotonaldehyde and cyclopentadiene^a

Entry	Cycle	Leaching of catalyst^b (mg)	Conversion^c (%)	exo/endo^d	ee^e (%) endo
a IL 8 (5 mol%, 14 mg) was dissolved in CH3CN–water (95 : 5, 1 mL), trifluoroacetic acid (5 mol%), crotonaldehyde (0.5 mmol, 42 μL) and cyclopentadiene (0.5 mmol, 41 μL) were added and stirred at room temperature for 24 h.b Leaching of the catalyst was determined by HPLC and details are given in the ESI.c Conversion checked by gas chromatography.d Diastereomeric ratio was calculated by Gas Chromatography.e ee was determined by Gas Chromatography using β-Dex chiral column.
1	0	0.12	94	1 : 1.1	90
2	1	0.10	90	1 : 1.1	89
3	2	0.00	88	1 : 1.1	88
4	3	0.01	87	1 : 1.1	88
5	4	0.02	81	1 : 1.1	88
6	5	0.02	81	1 : 1.1	87

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Experimental

Materials and methods

The cyclopentadiene was prepared from its dimer. Crotonaldehyde was freshly distilled and used. Proton and carbon nuclear magnetic resonance spectra (¹H and ¹³C NMR, respectively) were recorded on a 400 MHz Jeol-FT-NMR spectrometer at ambient temperature (operating frequencies: ¹H, 400.13 MHz; ¹³C, 100.61 MHz). The chemical shifts (δ) for all compounds are listed in parts per million downfield from tetramethylsilane using the NMR solvent as an internal reference. The reference values used for deuterated chloroform (CDCl₃) and were 7.26 and 77.00 ppm for ¹H and ¹³C NMR spectra, respectively. HRMS analysis was carried out using an Agilent G6530AA LC Q-TOF mass spectrometer. Thin layer chromatography was carried out using Merck Kieselgel 60 F254 silica gel plates. Column chromatography separations were performed using silica gel 230–400 mesh. All the new synthesized compounds were characterized by ¹H, ¹³C NMR and HRMS and known compounds were characterised by ¹H and ¹³C NMR. The experimental procedures for the known compounds were according to literature reports and are given in the ESI.† The enantiomeric excess of Diels–Alder products was determined on Shimadzu LC-2010HT using OD-H and AD-H chiral columns and Shimadzu GC-2010 plus using β-Dex chiral column. Optical rotations was recorded using a Rudolph digipol polarimeter.

Synthetic procedures

2-((5R)-5-Benzyl-2,2-dimethyl-4-oxopyrrolidin-3-yl)ethyl 5-bromopentanoate (5). In a 100 mL round bottom flask, anhydrous CH₃SO₃H (12 mL) was cooled in an ice–water bath and compound 4 (2.83 g, 10 mmol) was added in 20 min followed by the addition of 5-bromopentanoyl chloride and the reaction mixture was stirred at 0–5 °C for 3.5 h. The clear solution was diluted with diethyl ether and transferred to a separatory funnel and more diethyl ether was added to give phase separation. The bottom yellow layer of the product was allowed to drip directly into a mixture of dichloromethane (60 mL) and aq. solution of K₂CO₃ (12.0 g dissolved in 70 mL). After complete addition, the organic phase was separated. The aq. phase was extracted with dichloromethane (2 × 30 mL) and the combined solvent was dried over anhydrous Na₂SO₄ and concentrated in vacuum. The product 5 was further purified by column chromatography using a mixture of hexane–ethyl acetate (70 : 30) to afford a yellow liquid (2.86 g, 70%). [α]²⁵_D = −36.6 (c 1.0, CHCl₃); ¹H NMR (CDCl₃, 400 MHz) δ 7.25–7.15 (m, 5H), 4.13–4.07 (m, 2H), 3.74 (t, 1H, J = 5.49 Hz), 3.51–3.46 (m, 1H), 3.36 (t, 2H, J = 6.59 Hz), 3.37–3.33 (m, 1H), 3.16–3.11 (m, 1H), 3.03 (d, 1H, J = 5.86 Hz), 2.24 (t, 2H, J = 7.69 Hz), 1.86–1.79 (m, 2H), 1.74–1.68 (m, 2H), 1.22 (s, 3H), 1.11 (s, 3H) ppm. ¹³C NMR (CDCl₃, 100 MHz) δ 174.1, 173.2, 136.4, 129.3 (2C), 128.3 (2C), 126.5, 75.7, 61.1, 58.4, 38.9, 36.6, 33.8, 31.1, 28.5, 27.6, 26.2, 24.4 ppm.

(R)-3-(5-(2-(4-Benzyl-2,2-dimethyl-5-oxoimidazolidin-1-yl)ethoxy)-5-oxopentyl)-1-methyl-1H-imidazol-3-ium bromide (6). Compound 5 (5 mmol, 2.04 g) and 1-methylimidazole (6 mmol, 0.492 g) were heated at 100 °C for 10 min and cooled to room temperature. The reaction mixture was washed with diethyl ether to remove the excess of 1-methylimidazole. The residue was dried under reduced pressure to afford compound 6 (2.21 g, 90%) as a light yellow hygroscopic liquid. [α]²⁵_D = −16.3 (c 1.2, MeOH); ¹H NMR (CDCl₃, 400 MHz) δ 10.13 (s, 1H), 7.52 (s, 1H), 7.45 (s, 1H), 7.24–7.13 (m, 5H), 4.32 (t, 2H, J = 7.63 Hz), 4.01 (s, 3H), 4.05–4.01 (m, 2H), 3.7–3.64 (m, 1H), 3.49–3.36 (m, 1H), 3.15–3.12 (m, 1H), 3.00–2.95 (m, 2H), 2.29 (t, 2H, J = 8.01 Hz), 1.94–1.89 (m, 2H), 1.61–1.57 (m, 2H), 1.20 (s, 3H), 1.11 (s, 3H) ppm. ¹³C NMR (CDCl₃, 100 MHz) δ 174.5, 172.5, 137.1, 136.7, 129.3 (2C), 128.4 (2C), 126.7, 123.3, 122.1, 75.9, 61.6, 58.6, 49.4 38.9, 36.9, 36.5, 32.7, 29.2, 27.8, 26.3, 20.9 ppm. HRMS (ESI) calcd for C₂₃H₃₃N₄O₃⁺ [M]⁺: 413.2547; found 413.2531.

(R)-3-(5-(2-(4-Benzyl-2,2-dimethyl-5-oxoimidazolidin-1-yl)ethoxy)-5-oxopentyl)-1-methyl-1H-imidazol-3-ium tetrafluoroborate (7). The ionic liquid 6 (1 mmol, 0.491 g) was dissolved in a mixture of water–acetone (1 : 1, 10 mL) and potassium tetrafluoroborate (1.2 mmol, 0.152 g) was added and the mixture was stirred at room temperature for overnight. After reaction, acetone was removed and the aqueous layer was extracted with CH₂Cl₂ (10 mL × 3). The combined organic layer was washed with water (5 mL × 3), dried with anhydrous Na₂SO₄, filtered and concentrated under vacuum to give ionic liquid 7 (0.373 g, 75%). [α]²⁵_D = −14.9 (c 1.0, CH₂Cl₂); ¹H NMR (CDCl₃, 400 MHz) δ 8.91 (s, 1H), 7.38 (s, 1H), 7.33 (s, 1H), 7.25–7.15 (m, 5H), 4.17 (t, 2H, J = 6.87 Hz), 4.12–4.04 (m, 2H), 3.88 (s, 3H), 3.72 (t, 1H, J = 6.10 Hz), 3.51–3.40 (m, 1H), 3.18–3.14 (m, 1H), 3.06–2.93 (m, 2H), 2.29 (t, 2H, J = 6.87 Hz), 1.90–1.85 (m, 2H), 1.60–1.56 (m, 2H), 1.22 (s, 3H), 1.14 (s, 3H) ppm. ¹³C NMR (CDCl₃, 100 MHz) δ 174.5, 172.6, 136.8, 136.4, 129.3 (2C), 128.5 (2C), 126.7, 123.5, 122.2, 76.0, 61.7, 58.7, 49.3, 38.9, 37.0, 36.1, 32.7, 29.0, 27.8, 26.3, 20.9 ppm. ¹⁹F NMR (CDCl₃, 304 MHz) δ −150.9 (s). HRMS (ESI) calcd for C₂₃H₃₃N₄O₃⁺ [M]⁺: 413.2547; found 413.2564.

(R)-3-(5-(2-(4-Benzyl-2,2-dimethyl-5-oxoimidazolidin-1-yl)ethoxy)-5-oxopentyl)-1-methyl-1H-imidazol-3-ium hexafluorophosphate (8). The ionic liquid 6 (3 mmol, 1.47 g) was dissolved in a mixture of water–acetone (1 : 1, 30 mL) and potassium hexafluorophosphate (3.6 mmol, 0.66 g) was added and the mixture was stirred at room temperature for overnight. After reaction, acetone was removed and the aqueous layer was extracted with CH₂Cl₂ (30 mL × 3), the combined organic layer was washed with water (15 mL × 3), dried over anhydrous Na₂SO₄, filtered and concentrated under vacuum to give ionic liquid 8 (1.35 g, 81%). [α]²⁵_D = −19.7 (c 1.0, CH₂Cl₂); ¹H NMR (CDCl₃, 400 MHz) δ 8.52 (s, 1H), 7.31–7.16 (m, 7H), 4.14–4.05 (m, 4H), 3.84 (s, 3H), 3.74–3.67 (m, 1H), 3.42–3.53 (m, 1H), 3.19–3.16 (m, 1H), 3.07–3.03 (m, 1H), 2.98–2.93 (m, 1H), 2.29 (t, 2H, J = 6.48, Hz), 1.91–1.85 (m, 2H), 1.62–1.55 (m, 2H), 1.23 (s, 3H), 1.15 (s, 3H) ppm. ¹³C NMR (CDCl₃, 100 MHz) 174.6, 172.7, 136.9, 136.0, 129.4 (2C), 128.5 (2C), 126.8, 123.5, 122.1, 76.1, 61.7, 58.7, 49.4, 39.0, 37.0, 36.1, 32.7, 28.9, 27.8, 26.3, 20.9 ppm. ¹⁹F NMR (CDCl₃, 304 MHz) δ −71.9 (d, J = 563.74 Hz). ³¹P NMR (CDCl₃, 162 MHz) δ −144.0 (septet, J = 758.75 Hz). HRMS (ESI) calcd for C₂₃H₃₃N₄O₃⁺ [M]⁺: 413.2547; found 413.2530.

General procedure of enantioselective Diels–Alder reduction

IL 8 (5 mol%, 14 mg) was taken in acetonitrile–water (95 : 5) (1 mL) and TFA (5 mol%) was added and stirred for 5 min, then α,β-unsaturated aldehyde (0.5 mmol) was added and the reaction mixture was stirred for 10 min at r.t. Finally, cyclopentadiene (0.5 mmol) was added and the reaction was stirred at r.t. for a specified time. Conversion was monitored by GC in the case of crotonaldehyde and for other reagents it was checked by TLC using hexane–EtOAc (80 : 20). The solvent was evaporated by rotavapor and the products were purified by column chromatography.

Procedure for recycling of catalyst

After each fresh catalytic cycle of the reaction, the solvent was passed through a pad of anhydrous sodium sulfate to remove the water from the reaction. The solvent of the reaction mixture was removed under vaccum and hexane–diethyl ether (5 mL, 1 : 1) was added, IL 8 separated as viscous liquid and the product was in solution which was decanted off. The residue IL 8 was dissolved in acetonitrile–water (95 : 5) and TFA (5 mol%) was added and resulting mixture was stirred at r.t. for 10 min, followed by addition of crotonaldehyde (0.5 mmol) and cyclopentadiene (0.5 mmol). The reaction was monitored by GC. The solvent was evaporated by rotavapor. A similar procedure was followed for next catalytic run.

Conclusions

In conclusion, we have developed an efficient method for an enantioselective Diels–Alder reaction catalyzed by recoverable MacMillan catalyst modified with imidazolium ionic liquid at room temperature. IL 8 (5 mol%) acts as catalyst in the presence of co-catalyst trifluoroacetic acid (5 mol%) for the Diels–Alder reaction between cyclopentadiene and crotonaldehyde to give 94% conversion of product with exo/endo (1 : 1.1) and 90% ee of endo product, which is comparable to unmodified MacMillan catalyst and better than other reported reusable catalysts. Ionic liquid supported MacMillan catalyst 8 can be recovered and reused for up to 5 cycles with minor decrease in conversions Diels–Alder, but ee’s were in the range of 90–87%.

Acknowledgements

SS acknowledges financial assistance from the Science and Engineering Research Board (SERB), Department of Science and technology (DST), India, under the scheme Fast Track Young Scientist (SB/FT/CS-020/2012) and the University Science Instrumentation Center (USIC), University of Delhi, India, for analytical data. The authors are thankful to DU-DST mass facility at USIC. MSC is thankful to the University Grant Commission (UGC), New Delhi, for providing SRF.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra09710j

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