Calix[4]arene cyclohexanediamine derivatives and green catalytic asymmetric Aldol reactions thereof

Abstract

The present invention relates to the technical field of catalytic organic synthesis, and in particular to a calix[4]arene cyclohexanediamine derivative and a method for green catalytic asymmetric Aldol reaction thereof. Aromatic aldehyde and cyclic ketone are used as raw materials, a calix[4]arene cyclohexanediamine derivative is used as a phase transfer catalyst, p-nitrobenzoic acid is used as an additive, and water is used as a solvent. The reaction is carried out at 25°C for 24 to 48 hours. After the reaction is completed, dichloromethane is added, and the organic phase is extracted and separated. The organic phase is dried with anhydrous Na2SO4, and purified by column chromatography to obtain an Aldol product. The synthesis process conditions of the calix[4]arene cyclohexanediamine derivative of the present invention are mild, the catalytic reaction efficiency is high, the asymmetric Aldol reaction catalyzed by the derivative uses water as a solvent, is green and environmentally friendly, and the catalytic reaction can obtain good dr value and ee value under room temperature conditions, thus having broad application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of catalytic organic synthesis, in particular to a calix[4]arene cyclohexanediamine derivative and a method for green catalytic asymmetric Aldol reaction thereof. Background Art

[0002] In recent years, with the increasing understanding and in-depth study of the concept of chirality, controlling the optical selectivity and diastereoselectivity of aldol reactions has become an important research topic. Asymmetric aldol reactions catalyzed by small organic molecules and metal complexes have been extensively reported in the literature, but the catalysts used in these reactions still have some disadvantages, such as being environmentally harmful, non-renewable, highly toxic, unstable, and requiring low temperatures.

[0003] Chiral cyclohexanediamine derivatives are often used in the study of catalytic asymmetric Aldol reactions. In 2023, the Guo team successfully designed and synthesized a (1R,2R)-1,2-cyclohexanediamine pendant helical polyphenylisocyanate-supported catalyst 1, which can catalyze the organic asymmetric Aldol reaction of p-nitrobenzaldehyde and cyclohexanone with an enantioselectivity of 49% ee and a diastereoselectivity of 60:40dr. In 2021, Sato et al. designed and synthesized a bifunctional immobilized polymer catalyst 2 based on a proline amide combination, which is intended for use in Aldol reactions in a flow system. The two functions of the catalyst are located on different grafted polymers, and the interaction between the grafted polymers promotes high conversion and high enantioselectivity of the asymmetric Aldol reaction.

[0004]

[0005] However, the synthesis of these catalysts is complicated, the preparation conditions are harsh, and the cost is high, making them difficult to apply in industry. Therefore, the development of a new type of low-cost, easy-to-synthesize, and efficient green catalyst remains the core content of current research in this field. Summary of the Invention

[0006] The present invention provides a calix[4]arene cyclohexanediamine derivative and a method for green catalysis of an asymmetric aldol reaction. The cavity structure of the calixarene interacts with the phase transfer functional group, effectively controlling the substrate within a certain space, thereby achieving a highly efficient catalytic effect.

[0007] The technical solution adopted by the present invention to solve the technical problem is: a calix[4]arene cyclohexanediamine derivative, whose structural formula is:

[0008]

[0009] The method for green catalysis of asymmetric Aldol reaction using the derivative comprises the following steps:

[0010] (1) Using aromatic aldehyde and cyclic ketone as raw materials, calix[4]arene cyclohexanediamine derivative as phase transfer catalyst, p-nitrobenzoic acid as additive, and water as solvent, an Aldol catalytic reaction is carried out; the reaction temperature is 25°C, and the reaction time is 24 to 48 hours;

[0011] Among them, the aromatic aldehyde is benzaldehyde, substituted benzaldehyde, naphthaldehyde, pyridinealdehyde or thiophenealdehyde; among them, the substituted benzaldehyde is a benzaldehyde in which the hydrogen on the benzene ring is replaced by 1 to 2 substituents, and the substituents are one or more of fluorine, chlorine, bromine, iodine, nitro, cyano, trifluoromethyl, and phenyl.

[0012] The cyclic ketone is cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone, pyrone or thiophenone.

[0013] The molar ratio of aromatic aldehyde to cyclic ketone is 1:1-2; the amount of catalyst used is 2 mol% of the aromatic aldehyde; the amount of p-nitrobenzoic acid used is 2 mol% of the aromatic aldehyde; and the amount of water used when 0.5 mmol of aromatic aldehyde participates in the reaction is 1-2 mL.

[0014] (2) After the reaction in step (1) is completed, dichloromethane is added, the organic phase is extracted and separated, washed with saturated brine, and dried over anhydrous sodium sulfate; and separated by column chromatography to obtain the Aldol product.

[0015] The beneficial effects of the present invention are as follows: the method for green catalysis of asymmetric Aldol reaction of calix[4]arene cyclohexane diamine derivatives provided by the present invention, wherein the chemical bonds modified on the upper edge of the calixarene are amide bonds and primary amine bonds, thereby being able to completely rely on the catalytic center modified on the upper edge to establish a chiral environment. The calixarene derivatives have hydrophobic groups and hydrophilic groups on their skeleton structure, which can effectively connect the aqueous phase and the organic phase during the catalytic reaction, thereby exerting the function of phase transfer catalysis, and have high selectivity for cyclic ketones of different sizes. The synthesis process conditions of the calix[4]arene cyclohexane diamine derivatives are mild, high synthesis yield, high catalytic efficiency, good stereoselectivity, etc. The present invention will provide a new approach to expand the ideas for chiral modification of calixarene and enrich the chemical methods for chiral modification of the upper edge of calixarene. DETAILED DESCRIPTION

[0016] The present invention will be further described below with reference to specific examples. It should be understood that the examples are only used to illustrate the present invention but not to limit the scope of the present invention.

[0017] Example 1

[0018] 1. Synthesis of Calix[4]cyclohexanediamine Catalyst I

[0019]

[0020] 5-Formyl-25,26,27,28-tetrapropoxycalix[4]arene (620 mg, 1 mmol), cyclohexanediaminoacetyl (314 mg, 2 mmol), and 100 mg of anhydrous sodium sulfate were weighed in a round-bottom flask with methanol (20 mL) as the solvent. The reaction was refluxed and monitored by TLC until the reaction of the starting materials was complete. Sodium borohydride (189 mg, 5 mmol) was added in two batches under ice-water bath conditions. The reaction temperature was raised to 60°C and monitored by TLC until the reaction of the starting materials was complete. The reaction was quenched, the reaction solution was concentrated, and extracted with water and dichloromethane. The organic phases were collected, combined, concentrated, and recrystallized from dichloromethane / acetonitrile to obtain the pure calixarene imine intermediate compound (525 mg, 69% yield).

[0021] White solid; Mp: 1 H NMR (300MHz, CDCl3) δ6.58–6.38(m,11H),5.43(d,J=7.0Hz,1H),4.37(d,J=13.3Hz,4H),3.76(t,J=7.5Hz,8H),3.53–3.35(m,2H),3.26(d,J=12.8Hz ,1H),3.12–2.99(m,4H),2.19–2.05(m,1H),1.99(d,J=9.4Hz,1H),1.92–1 .77(m,12H),1.72–1.54(m,1H),1.30–1.02(m,4H),0.91(t,J=7.4Hz,12H). 13 C NMR (75MHz, CDCl3) δ170.30,156.78,156.65,156.58,155.75,135.34,135.30,135.28,135.16,135.10,135.04,135.03,133.88,128.19,128.15 ,128.13,128.07,127.97,127.90,121.98,121.90,121.65,76.77,59.82 ,53.42,49.98,32.63,31.82,31.07,24.93,24.77,23.80,23.31,10.42.

[0022]

[0023] The calixarene imine intermediate (761 mg, 1 mmol) and potassium carbonate (1.1 g, 8 mmol) were weighed sequentially into a round-bottom flask with dichloromethane (40 mL) as the solvent. The mixture was stirred at 0°C for 1 h. Benzyl bromide (1.92 mL, 8 mmol) was added and stirred at room temperature. The reaction progress was monitored by TLC. After 6 h, the starting materials reacted completely. The reaction solution was concentrated and recrystallized from dichloromethane / acetonitrile to obtain the pure acetyl-protected cyclohexanediamine calixarene intermediate. The intermediate was then added to a round-bottom flask with CH3OH (30 mL) as the solvent. 36% HCl (1.5 mL) was added dropwise in three portions. The mixture was refluxed for 24 h. The reaction was stopped and extracted three times with water and dichloromethane. The organic phases were combined and concentrated, and recrystallized from dichloromethane / acetonitrile to obtain Compound I (495 mg, 68% yield).

[0024] White solid; Mp: 81℃; 1 H NMR (300MHz, CDCl3) δ7.40–7.12(m,5H),6.71–6.40(m,10H),6.29(t,J=7.5Hz,1H),4.43(d,J=13.2Hz,4H),3.91–3.73(m,8H),3.55(dd,J =30.1,13.5Hz,2H),3.29–2.93(m,6H),2.67–2.48(m,1H),2.17–2.02(m,1H),2.02–1.83(m,10H),1.79–1.55(m,4H),1.14–0.90(m,16H). 13 C NMR (75MHz, CDCl3) δ156.69,156.65,156.59,155.53,140.48,135.32,135.28,135.07 ,135.01,134.77,134.75,133.23,129.08,128.61,128.29,128.23,128.18,128.13,12 6.76,122.01,121.78,76.88,76.83,76.80,64.61,53.91,52.99,51.38,35.18,31.17,31.09,31.06,25.93,25.35,23.40,23.35,23.30,22.67,10.50,10.46,10.43,10.41.

[0025] 2. Synthesis of Calix[4]cyclohexanediamine Catalyst II

[0026]

[0027] The calixarene imine intermediate (761 mg, 1 mmol) and potassium carbonate (1.1 g, 8 mmol) were weighed sequentially into a 100 mL round-bottom flask with acetonitrile as the solvent (40 mL). The mixture was stirred at room temperature for 1 h. Ethyl iodide (0.64 mL, 8 mmol) was added and the mixture was refluxed for 12 h. The reaction was terminated and extracted three times with dichloromethane and water. The organic phase was concentrated and recrystallized from dichloromethane / acetonitrile to obtain pure acetyl-protected cyclohexanediamine calixarene intermediate. The intermediate was then added to a 50 mL round-bottom flask and CH3OH as the solvent (30 mL). 36% HCl (1.5 mL) was added dropwise in three batches. The mixture was refluxed for 24 h. The reaction was terminated and extracted three times with dichloromethane and water. The organic phase was concentrated and recrystallized from dichloromethane / acetonitrile to obtain compound II (526 mg, 88% yield).

[0028] Yellow solid; Mp: 57°C; 1 H NMR (300MHz, CDCl3) δ6.67–6.52(m,11H),4.50–4.38(m,4H),3.89–3.78(m,8H),3.51(d,J=14.0Hz,1H),3.18–3.09(m,4H),3.03(d,J=14.1Hz, 1H),2.58–2.49(m,1H),2.38–2.21(m,2H),2.18–2.11(m,1H),1.99–1.8 7(m,9H),1.83–1.60(m,5H),1.22–0.96(m,16H),0.91(t,J=7.0Hz,3H). 13 C NMR (75MHz, CDCl3) δ156.73,156.58,156.54,155.38,135.30,135.25,135.22,135. 15,135.09,134.98,134.77,134.71,133.96,128.26,128.17,128.09,127.79,122.0 3,121.95,121.75,77.36,76.88,76.83,76.80,76.77,65.17,52.96,51.30,43.52,35.25,31.12,31.05,26.12,25.27,23.39,23.33,23.06,14.54,10.47,10.44,10.42.

[0029] 3. Synthesis of Calix[4]cyclohexanediamine Catalyst III

[0030]

[0031] The calixarene imine intermediate (761 mg, 1 mmol) and potassium carbonate (1.1 g, 8 mmol) were weighed into a 100 mL round-bottom flask with acetonitrile as the solvent (40 mL). The mixture was stirred at room temperature for 1 h. Iodohexane (1.1 mL, 8 mmol) was added and the mixture was refluxed for 12 h. The reaction was stopped and extracted three times with dichloromethane and water. The organic phase was concentrated and recrystallized from dichloromethane / acetonitrile to obtain pure acetyl-protected cyclohexanediamine calixarene intermediate. The intermediate was then added to a 50 mL round-bottom flask and CH3OH as the solvent (30 mL). 36% HCl (1.5 mL) was added dropwise in three batches. The mixture was refluxed for 24 h. The reaction was stopped and extracted three times with dichloromethane and water. The organic phase was concentrated and recrystallized from dichloromethane / acetonitrile to obtain compound III (337 mg, 60% yield).

[0032] Yellow solid; Mp: 49°C; 1 H NMR (300MHz, CDCl3) δ6.82–6.56(m,5H),6.47(s,6H),4.44(dd,J=13.4,5.7Hz,4H),3.94–3.74(m,8H),3.52(d,J=13.7Hz,1H),3.22–3.01(m,5H ),2.62–2.48(m,1H),2.49–2.33(m,1H),2.35–2.21(m,1H),2.13(t,J=9 .4Hz,1H),2.04–1.67(m,13H),1.42–1.10(m,12H),1.07–0.83(m,16H). 13 C NMR (75MHz, CDCl3) δ157.06,156.32,156.30,155.72,135.76,135.72,135.20,135.16,134.8 9,134.83,134.79,134.77,133.89,128.82,128.41,128.33,127.99,127.94,121.99,121.75 ,77.36,76.86,76.83,76.78,65.52,53.60,51.34,49.81,34.90,32.00,31.11,31.06,29.13,27.30,26.04,25.26,23.43,23.40,23.33,23.28,22.89,22.85,14.29,10.57,10.38,10.32.

[0033] 4. Synthesis of Calix[4]cyclohexanediamine Catalyst IV

[0034]

[0035] The calixarene imine intermediate (761 mg, 1 mmol) and potassium carbonate (1.1 g, 8 mmol) were weighed into a 100 mL round-bottom flask with acetonitrile as the solvent (40 mL). The mixture was stirred at room temperature for 1 h, and 2-iodopropane (0.8 mL, 8 mmol) was added. The mixture was refluxed for 12 h, then the reaction was stopped. The mixture was extracted three times with dichloromethane and water. The organic phase was concentrated and recrystallized from dichloromethane / acetonitrile to obtain pure acetyl-protected cyclohexanediamine calixarene intermediate. The intermediate was then added to a 50 mL round-bottom flask. Using CH3OH as the solvent (30 mL), 36% HCl (1.5 mL) was added dropwise in three portions. The mixture was refluxed for 24 h, the reaction was stopped, and the mixture was extracted three times with dichloromethane and water. The organic phase was concentrated and recrystallized from dichloromethane / acetonitrile to obtain compound IV (416 mg, 78% yield).

[0036] Yellow solid; Mp: 71°C; 1 H NMR (300MHz, CDCl3) δ6.72–6.47(m,11H),4.44(dd,J=13.3,5.8Hz,4H),3.83(t,J=7.5Hz,8H),3.48(d,J=14.2Hz,1H) ,3.31–3.02(m,5H),2.94–2.73(m,1H),2.52–2.34(m,1H),2.23–2.05(m,1H),2.00–1.55(m,14H),1.35–0.88(m,22H). 13 C NMR (75MHz, CDCl3) δ156.77,156.54,156.50,155.32,135.35,135.33,135.22,135.18, 135.10,135.04,134.85,134.72,134.57,128.18,128.15,128.13,128.10,128.06,128 .04,127.84,122.00,121.93,121.65,76.81,76.79,62.64,51.83,48.64,48.02,35.08,31.09,31.03,28.19,26.38,25.37,23.37,23.34,23.31,22.96,18.60,10.45,10.39.

[0037] Example 2

[0038] The catalytic effects of calix[4]cyclohexanediamine derivatives I to IV were screened. The experimental method was as follows: p-nitrobenzaldehyde (0.5 mmol), cyclohexanone (0.5 mmol), calixarene catalyst (2 mol%), p-nitrobenzoic acid (2 mol%), and water (1.5 mL) were added to a test tube in sequence. The reaction was stirred at 25°C for 24 hours and then the reaction was completed. After the reaction was completed, the reaction solution was concentrated and separated by chromatography (ethyl acetate: petroleum ether = 1:5) to obtain the Aldol addition product.

[0039] 1. Using calixarene catalyst I, the yield of the target product was 88%, the anti / syn ratio was 59:41, and the ee of the anti product was 88%;

[0040] 2. Using calixarene catalyst II, the yield of the target product was 94%, the anti / syn ratio was 87:13, and the ee of the anti product was 94%;

[0041] 2. Using calixarene catalyst III, the yield of the target product was 90%, the anti / syn ratio was 80:20, and the ee of the anti product was 90%;

[0042] 2. Using calixarene catalyst IV, the yield of the target product was 91%, the anti / syn ratio was 64:36, and the ee of the anti product was 91%.

[0043] Example 3

[0044] The solvent dosage for the reaction was screened. The experimental method was as follows: p-nitrobenzaldehyde (0.5 mmol), cyclohexanone (0.5 mmol), calixarene catalyst II (2 mol%), p-nitrobenzoic acid (2 mol%), and water were added sequentially to a test tube. The reaction was stirred at 25°C for 24 hours before the reaction was completed. After the reaction was completed, the reaction solution was concentrated and separated by chromatography (ethyl acetate:petroleum ether = 1:5) to obtain the Aldol addition product.

[0045] 1. The amount of water used was 0.5 mL, the yield of the target product was 68%, the anti / syn ratio was 86:14, and the ee of the anti product was 93%;

[0046] 2. The amount of water used was 1 mL, the yield of the target product was 92%, the anti / syn ratio was 87:13, and the ee of the anti product was 93%;

[0047] 3. The amount of water used was 1.5 mL, the yield of the target product was ≥99%, the anti / syn ratio was 87:13, and the ee of the anti product was 94%;

[0048] 4. The amount of water used was 2 mL, the yield of the target product was ≥99%, the anti / syn ratio was 63:37, and the ee of the anti product was 94%.

[0049] Example 4

[0050] The optimal experimental conditions in Example 3 were used to investigate the applicability of aldehyde substrates for the catalytic asymmetric reaction. The experimental method was as follows: p-nitrobenzaldehyde (0.5 mmol), cyclohexanone (0.5 mmol), calixarene catalyst II (2 mol%), p-nitrobenzoic acid (2 mol%), and water (1.5 mL) were sequentially added to a test tube. The reaction was stirred at 25°C for 24 hours before completion. After completion, the reaction solution was concentrated and separated by chromatography (ethyl acetate:petroleum ether = 1:5) to obtain a pure aldol addition product with a yield of ≥99%, an anti / syn ratio of 87:13, and an anti product ee of 94%.

[0051] Example 5

[0052] This example is the same as Example 4, except that o-nitrobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 87%, an anti / syn ratio of 71:29, and an ee of the anti product of 93%.

[0053] Example 6

[0054] This example is the same as Example 4, except that m-nitrobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 92%, an anti / syn ratio of 75:25, and an ee of the anti product of 87%.

[0055] Example 7

[0056] This example is the same as Example 4, except that m-2,4-dinitrobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 91%, an anti / syn ratio of 86:14, and an ee of the anti product of 91%.

[0057] Example 8

[0058] This example is the same as Example 4, except that p-cyanobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 93%, an anti / syn ratio of 74:26, and an ee of the anti product of 93%.

[0059] Example 9

[0060] This example is the same as Example 4, except that p-trifluoromethylbenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 93%, an anti / syn ratio of 87:13, and an ee of the anti product of 93%.

[0061] Example 10

[0062] This example is the same as Example 4, except that 2-fluorobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 77%, an anti / syn ratio of 99:1, and an ee of the anti product of 93%.

[0063] Example 11

[0064] This example is the same as Example 4, except that 4-fluorobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 72%, an anti / syn ratio of 75:25, and an ee of the anti product of 93%.

[0065] Example 12

[0066] This example is the same as Example 4, except that 4-chlorobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 70%, an anti / syn ratio of 61:39, and an ee of the anti product of 88%.

[0067] Example 13

[0068] This example is the same as Example 4, except that 3-chlorobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 80%, an anti / syn ratio of 70:30, and an ee of the anti product of 89%.

[0069] Example 14

[0070] This example is the same as Example 4, except that 4-bromobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 77%, an anti / syn ratio of 64:36, and an ee of the anti product of 88%.

[0071] Example 15

[0072] This example is the same as Example 4, except that 2-iodobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 83%, an anti / syn ratio of 71:29, and an ee of the anti product of 95%.

[0073] Example 16

[0074] This example is the same as Example 4, except that benzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 72%, an anti / syn ratio of 65:35, and an ee of the anti product of 84%.

[0075] Example 17

[0076] This example is the same as Example 4, except that 1-naphthylbenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 63%, an anti / syn ratio of 57:43, and an ee of the anti product of 86%.

[0077] Example 18

[0078] This example is the same as Example 4, except that 2-naphthylbenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 85%, an anti / syn ratio of 76:24, and an ee of the anti product of 89%.

[0079] Example 19

[0080] This example is the same as Example 4, except that p-phenylbenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 75%, an anti / syn ratio of 67:33, and an ee of the anti product of 96%.

[0081] Example 20

[0082] This example is the same as Example 4, except that p-2-pyridinecarboxaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 84%, an anti / syn ratio of 68:32, and an ee of the anti product of 89%.

[0083] Example 21

[0084] This example is the same as Example 4, except that p-5-phenyl-2-thiophenecarboxaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 55%, an anti / syn ratio of 64:36, and an ee of the anti product of 83%.

[0085] Example 22

[0086] This example refers to Example 4, but uses cyclobutanone instead of cyclohexanone to obtain a pure Aldol addition product with a yield of >50%, an anti / syn ratio of 37:63, and an anti product ee of 34%.

[0087] Example 23

[0088] This example is the same as Example 4, except that cyclopentanone is used instead of cyclohexanone to obtain the Aldol addition product with a yield of 75%, an anti / syn ratio of 56:44, and an ee of the anti product of 92%.

[0089] Example 24

[0090] This example is the same as Example 4, except that cycloheptanone is used instead of cyclohexanone to obtain the Aldol addition product with a yield of 66%, an anti / syn ratio of 46:54, and an ee of the anti product of 64%.

[0091] Example 25

[0092] This example is the same as Example 4, except that tetrahydrothiopyranone is used instead of cyclohexanone to obtain the Aldol addition product with a yield of 63%, an anti / syn ratio of 59:41, and an ee of the anti product of 80%.

[0093] Example 26

[0094] This example is the same as Example 4, except that tetrahydropyrone is used instead of cyclohexanone to obtain the Aldol addition product with a yield of 60%, an anti / syn ratio of 44:56, and an ee of the anti product of 81%.

[0095] Comparative Example 1

[0096] This comparative example is the same as Example 4, except that acetic acid is used instead of p-nitrobenzoic acid as an additive to obtain an Aldol addition product with a yield of 26%, an anti / syn ratio of 80:20, and an ee of the anti product of 92%.

[0097] Comparative Example 2

[0098] This comparative example is the same as Example 4, except that trifluoroacetic acid is used instead of p-nitrobenzoic acid as an additive to obtain an Aldol addition product with a yield of 61%, an anti / syn ratio of 81:19, and an ee of the anti product of 91%.

[0099] Comparative Example 3

[0100] This comparative example is the same as Example 4, except that an excess of cyclohexanone itself was used as the solvent to obtain the Aldol addition product with a yield of 50%, an anti / syn ratio of 41:59, and an ee of the anti product of 45%.

[0101] With the above-described preferred embodiments of the present invention as a guide, and with reference to the above description, relevant personnel are fully capable of making various changes and modifications without departing from the technical scope of this invention. The technical scope of this invention is not limited to the contents of the specification and must be determined according to the scope of the claims.

Claims

1. A calix[4]arene cyclohexanediamine derivative, characterized in that The structure of the calix[4]arene cyclohexanediamine derivative is shown below:

2. A use of the calix[4]arene cyclohexanediamine derivative according to claim 1, characterized in that: The calix[4]arene cyclohexanediamine derivative is used to catalyze the asymmetric aldol reaction of aromatic aldehydes and cyclic ketones.

3. The use of the calix[4]arene cyclohexanediamine derivative according to claim 2, characterized in that: The method steps of catalyzing the asymmetric Aldol reaction of aromatic aldehydes and cyclic ketones are as follows: (1) Using aromatic aldehyde and cyclic ketone as raw materials, calix[4]arene cyclohexanediamine derivative as phase transfer catalyst, p-nitrobenzoic acid as additive, and water as solvent, the reaction was carried out at 25°C for 24-48 hours; (2) After the reaction in step (1) is completed, dichloromethane is added, the organic phase is extracted and separated, washed with saturated brine, and dried over anhydrous sodium sulfate; and separated by column chromatography to obtain the Aldol product.

4. The use of the calix[4]arene cyclohexanediamine derivative according to claim 3, characterized in that: The aromatic aldehyde in step (1) is benzaldehyde, substituted benzaldehyde, naphthaldehyde, pyridinealdehyde or thiophenealdehyde; wherein the substituted benzaldehyde is a benzaldehyde in which the hydrogen on the benzene ring is replaced by 1 to 2 substituents, and the substituents are one or more of fluorine, chlorine, bromine, iodine, nitro, cyano, trifluoromethyl and phenyl.

5. The use of the calix[4]arene cyclohexanediamine derivative according to claim 3, characterized in that: The cyclic ketone in step (1) is cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone, pyrone or thiopyranone.

6. The use of the calix[4]arene cyclohexanediamine derivative according to claim 3, characterized in that: The molar ratio of the aromatic aldehyde to the cyclic ketone in step (1) is 1:1-2; the amount of catalyst used is 2 mol% of the aromatic aldehyde; the amount of p-nitrobenzoic acid used is 2 mol% of the aromatic aldehyde; and the amount of water used when 0.5 mmol of aromatic aldehyde participates in the reaction is 1-2 mL.

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