Chiral triazol-oxazoline compound and preparation method and application thereof

Abstract

The application relates to a chiral triazole-oxazoline compound and a preparation method and application thereof, and belongs to the technical field of organic synthesis. The chiral triazole-oxazoline compound has the structural formula: the preparation method comprises the steps of click reaction, triazole N2 substitution reaction, Suzuki coupling, triazole ester hydrolysis, amidation with a chiral amine alcohol and dehydration condensation. After a chiral triazole-oxazoline compound and a palladium salt compound are added to generate a catalyst in situ, asymmetric addition of aryl boronic acid on a carbon-carbon double bond of a prochiral organic compound is carried out to prepare a chiral organic compound. The application has the advantages of low raw material cost, few synthesis steps, low experiment site requirement, relatively mild reaction conditions and simple operation for preparing the novel triazole-oxazoline compound.

Description

Technical fields:

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a novel method for synthesizing chiral triazole-oxazoline compounds and the catalytic properties of these compounds as ligands in the palladium-catalyzed asymmetric 1,4-addition reaction of phenylboronic acid to β-substituted unsaturated cyclic ketones. Background technology:

[0002] Chiral oxazoline ligands possess exceptional properties in asymmetric synthesis, particularly their catalytic reactions with transition metals such as copper, palladium, and ruthenium, which have been a hot research topic in organic synthetic chemistry for the past three decades. Their high catalytic activity, chiral selectivity, and low-cost preparation methods have led to their widespread application. 1,2,3-triazole, a heterocyclic structure with multiple coordination sites and various coordination modes, is easy to prepare and modify, and has been reported as a ligand in a series of catalytic applications.

[0003] The current problem is that 1,2,3-triazole structures are rarely used in asymmetric catalysis, and related reports and applications are scarce. Although some chiral ligands possess 1,2,3-triazole structures, 1,2,3-triazole is more often used as a linking structure than for coordination. There are no examples of chiral oxazoline skeletons combined with 1,2,3-triazole structures to form chiral ligands for catalytic applications. However, the connection of these two heterocycles is technically feasible, and related synthetic work is significant for expanding the ligand library. Summary of the Invention:

[0004] The purpose of this invention is to overcome the problems existing in the prior art and provide a chiral triazole-oxazoline ligand and its preparation method, and to apply it to the asymmetric addition reaction of arylboronic acids to β-substituted cycloenones. The method of this invention starts with simple, readily available, and inexpensive achiral reagents and chiral pure raw materials, and efficiently synthesizes a series of triazole-oxazoline chiral ligands through a series of simple and easy-to-operate reaction pathways.

[0005] The technical solution of the present invention is as follows:

[0006] A chiral triazole-oxazoline compound, characterized in that the compound is of high optical purity, denoted as Compound 1, and has the following structural formula:

[0007]

[0008] Where R 1 It is hydrogen, methyl, or phenyl; R 2 It is tert-butyl, phenyl; R 3 It is either hydrogen or phenyl.

[0009] As shown above,

[0010] When R 1 For hydrogen, R 2 For tert-butyl, R 3 When it is hydrogen, it is denoted as compound 1a;

[0011] When R 1 It is methyl, R 2 It is a phenyl group, R 3 When it is hydrogen, it is denoted as compound 1b;

[0012] When R 1 It is a phenyl group, R 2 For tert-butyl, R 3 When it is hydrogen, it is denoted as compound 1c;

[0013] When R 1 It is a phenyl group, R 2 It is a phenyl group, R 3 When it is hydrogen, it is denoted as compound 1d;

[0014] When R 1 It is a phenyl group, R 2 It is a phenyl group, R 3 When it is phenyl, it is denoted as compound 1e;

[0015] The structural formulas of compounds 1a to 1e are as follows:

[0016]

[0017] A method for preparing a chiral triazole-oxazoline compound, characterized in that the steps include S1, S2, S5, S6, S7 or S3, S4, S5, S6, S7.

[0018] S1: Under inert gas protection, in an organic solvent, and with the aid of an oxidant, sodium azide reacts with compound 2 at 15–30°C for 12–36 hours to obtain compound 3; the molar ratio of compound 2, sodium azide, and oxidant is 1:1.5:2; the molar volume ratio of compound 2 to organic solvent is 0.2 mmol:1 mL; wherein, compound 2 is phenylethynyltrimethylsilane or 1-phenyl-1-propyne, and the oxidant is iodophenyldiacetic acid;

[0019] Preferably, the inert gas is nitrogen and / or argon; the solvent is anhydrous acetonitrile; and the reaction temperature is preferably 25°C.

[0020] S2: Under inert gas protection, in an organic solvent, and in the presence of a base and a catalyst, compound 3 and compound 4 combine and react at 50–70°C for 24–36 hours to obtain compound 5; the molar ratio of compound 3, compound 4, base, and catalyst is 1:1.05:3:0.05, and the molar volume ratio of compound 3 to organic solvent is 0.2 mmol:1 mL; wherein the base is potassium carbonate, the catalyst is potassium iodide, and compound 4 is ethyl 2-bromo-2-methylpropionate;

[0021] Preferably, the organic solvent is acetone.

[0022] S3: Under inert gas protection, in an organic solvent, and in the presence of a base and a catalyst, compound 6 combines with compound 4 and reacts at 50–70 °C for 24–36 hours to obtain compound 7; the molar ratio of compound 3, compound 4, base, and catalyst is 1:1.05:3:0.05, and the molar volume ratio of compound 6 to organic solvent is 0.2 mmol:1 mL; wherein the base is potassium carbonate, the catalyst is potassium iodide, and compound 6 is 4,5-dibromotriazole;

[0023] Preferably, the organic solvent is acetone.

[0024] S4: Under inert gas protection, compound 7, a base, and phenylboronic acid are added to a mixed solvent of organic solvent and water. The mixture is reacted at 80–100 °C for 24–36 hours in the presence of a palladium catalyst to obtain compound 8. The molar ratio of compound 7, phenylboronic acid, base, and palladium catalyst is 1:3:4:0.1, and the molar volume ratio of compound 7 to the mixed solvent is 0.2 mmol:1 mL. The base is potassium carbonate, and the palladium catalyst is tetrakis(triphenylphosphine)palladium.

[0025] Preferably, the mixed solvent is a mixture of 1,4-dioxane and water in a volume ratio of 3:1.

[0026] S5: In a mixed solvent of organic solvent and water, under the action of a strong base, compound 5 or compound 8 undergoes an ester hydrolysis reaction at 20–50°C for 2–12 hours, followed by neutralization with hydrochloric acid to obtain compound 9; the molar ratio of compound 5 or compound 8 to the strong base is 1:8, and the molar volume ratio of compound 5 or 8 to the organic solvent is 1 mmol:1 mL;

[0027] Preferably, the strong base is sodium hydroxide, the mixed solvent is a mixture of ethanol and water in a volume ratio of 2:1, and the hydrochloric acid is 2 mol / L concentrated hydrochloric acid.

[0028] S6: Under inert gas protection, compound 9, N-methylmorpholine, isobutyl chloroformate, and compound 10 are added sequentially to an organic solvent. Compound 9 and compound 10 undergo an amidation reaction at 0–20°C for 12–18 hours to obtain compound 11. The molar ratio of compound 9, N-methylmorpholine, isobutyl chloroformate, and compound 10 is 1:1.05:2.5:1.2. The molar volume ratio of compound 9 to the organic solvent is 0.2 mmol:1 mL. Compound 10 is S-tert-leucine, L-phenylglycine, or (S,S)-(-)-2-amino-1,2-diphenylethanol.

[0029] Preferably, the required inert gas is nitrogen and / or argon; the organic solvent is anhydrous tetrahydrofuran.

[0030] S7: Under inert gas protection, in an organic solvent, in the presence of p-dimethylaminopyridine, p-toluenesulfonyl chloride, and an organic amine, compound 11 undergoes a dehydration condensation reaction at 20–80 °C for 15–30 hours to obtain compound 1, namely the chiral triazole-oxazoline compound; the molar ratio of compound 11, p-dimethylaminopyridine, p-toluenesulfonyl chloride, and organic amine is 1:0.2:3:8; the molar volume ratio of compound 11 to the organic solvent is 0.1 mmol:1 mL.

[0031] Preferably, the inert gas is nitrogen and / or argon; the organic solvent is 1,2-dichloroethane; the organic amine is triethylamine; and the reaction temperature is 80°C.

[0032] The method described above in this invention can prepare a series of novel chiral triazole-oxazoline ligands.

[0033] An application of a chiral triazole-oxazoline compound involves the in-situ complexation of the chiral triazole-oxazoline compound and a palladium salt compound to generate a catalyst, followed by asymmetric addition of arylboronic acid to the carbon-carbon double bond of the pre-chiral organic compound to prepare a chiral organic compound with an ee value reaching 90%. The specific steps are as follows: under an oxygen atmosphere, arylboronic acid, compound 1, palladium trifluoroacetate, a Lewis acid, and an organic solvent are added sequentially. After stirring at room temperature for 5 minutes, a β-substituted unsaturated cyclic ketone is added, followed by heating at 20–80°C and sealing the reaction tube for 12–60 hours to obtain the chiral product.

[0034] Preferably, compound 1 is compound 1a or 1d, and the molar ratio of the β-unsaturated cyclic ketone, arylboronic acid, compound 1a or 1d, palladium trifluoroacetate, and Lewis acid is 1:2:0.1:0.075:0.15 or 1:2:0.17:0.15:0.15; the molar volume ratio of the β-unsaturated cyclic ketone to the organic solvent is 0.25 mmol:1 mL.

[0035] Preferably, the organic solvent is 1,2-dichloroethane; and the Lewis acid is ytterbium trifluoromethanesulfonate.

[0036] Preferably, the reaction temperature for the sealing reaction is 60 or 40°C, and the reaction time is 60 hours.

[0037] The beneficial effects of this invention are:

[0038] 1. The novel triazole-oxazoline compound prepared by this invention has the characteristics of low raw material cost, few synthesis steps, low experimental site requirements, relatively mild reaction conditions, and simple operation.

[0039] 2. The novel triazole-oxazoline compound of the present invention has the ability to perform asymmetric catalysis after in-situ binding with transition metals to form a catalyst. The resulting chiral product can have a high enantiomeric excess value and has practical application value. Attached image description:

[0040] Figure 1 The product compound 1a prepared in Example 9 1 1H NMR spectrum (solvent is deuterated chloroform).

[0041] Figure 2 The product compound 1a prepared in Example 9 13 C10 NMR spectrum (solvent is deuterated chloroform).

[0042] Figure 3 The product compound 1b prepared in Example 10 1 1H NMR spectrum (solvent is deuterated chloroform).

[0043] Figure 4 The product compound 1b prepared in Example 10 13 C10 NMR spectrum (solvent is deuterated chloroform).

[0044] Figure 5 The product compound 1c prepared in Example 17 1 1H NMR spectrum (solvent is deuterated chloroform).

[0045] Figure 6 The product compound 1c prepared in Example 17 13 C10 NMR spectrum (solvent is deuterated chloroform).

[0046] Figure 7 The product compound 1d prepared in Example 18 1 1H NMR spectrum (solvent is deuterated chloroform).

[0047] Figure 8The product compound 1d prepared in Example 18 13 C10 NMR spectrum (solvent is deuterated chloroform).

[0048] Figure 9 The product compound 1e prepared in Example 19 1 1H NMR spectrum (solvent is deuterated chloroform).

[0049] Figure 10 The product compound 1e prepared in Example 19 13 C10 NMR spectrum (solvent is deuterated chloroform).

[0050] Figure 11 The product compound (R)-3-methyl-3-phenylcyclohexan-1-one prepared in Example 20 1 1H NMR spectrum (solvent is deuterated chloroform).

[0051] Figure 12 The product compound (R)-3-methyl-3-phenylcyclohexan-1-one prepared in Example 20 13 C10 NMR spectrum (solvent is deuterated chloroform).

[0052] Figure 13 The product compound (R)-3-(4-fluorobenzyl)-3-phenylcyclo-hexan-1-one prepared in Example 21 1 1H NMR spectrum (solvent is deuterated chloroform).

[0053] Figure 14 The product compound (R)-3-(4-fluorobenzyl)-3-phenylcyclo-hexan-1-one prepared in Example 21 13 C10 NMR spectrum (solvent is deuterated chloroform).

[0054] Figure 15 The product compound (R)-3-(4-fluorobenzyl)-3-phenylcyclo-hexan-1-one prepared in Example 21 19 F NMR spectrum (solvent is deuterated chloroform). Detailed implementation method:

[0055] The present invention will be further illustrated below with specific examples. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the invention. Improvements and adjustments made by those skilled in the art based on the present invention in practical applications still fall within the scope of protection of the present invention.

[0056] Unless otherwise specified, the equipment and reagents used in this invention are commercially available products commonly used in this technical field.

[0057] The synthetic routes for compounds 1a and 1b in this invention are as follows:

[0058]

[0059] Example 1: Preparation of compound 3a

[0060] In a 100 mL round-bottom flask that had been dried in an oven and cooled, sodium azide (3.75 mmol) and iodophenyl diacetic acid (5.0 mmol) were added sequentially to an anhydrous acetonitrile solution of 2a (2.5 mmol) under an inert gas atmosphere. The mixture was stirred at room temperature for 12 hours. After the reaction was complete, silica gel was added and mixed thoroughly. The solvent was removed under reduced pressure, and the residue was subjected to column chromatography with petroleum ether:ethyl acetate as the eluent in a 1:1 ratio to give compound 3a, which was a yellow crystal.

[0061] 1 H NMR (400MHz, Chloroform-d) δ7.68–7.62(m,2H),7.48–7.38(m,3H),0.32(s,9H). 13 C NMR(101MHz, CDCl3)δ153.03,132.20,128.80,128.41,128.30,126.15,77.45,77.13,76.81,-0.79.HRMS(EI+)m / z calc'd for C 11 H 16 N3Si[M+H] + :218.1108,found218.1124.

[0062] Example 2: Preparation of compound 3b

[0063] In a 100 mL round-bottom flask that had been dried in an oven and cooled, sodium azide (3.75 mmol) and iodophenyl diacetic acid (5.0 mmol) were added sequentially to an anhydrous acetonitrile solution of 2b (2.5 mmol) under an inert gas atmosphere. The mixture was stirred at room temperature for 16 hours. After the reaction was complete, silica gel was added and mixed thoroughly. The solvent was removed under reduced pressure, and the residue was subjected to column chromatography with petroleum ether:ethyl acetate as the eluent in a 1:1 ratio to give compound 3b, which was a white crystal.

[0064] 1H NMR (400MHz, Chloroform-d) δ7.77–7.68(m,2H),7.50–7.44(m,2H),7.42–7.36(m,1H),2.55(s,3H). 13 C NMR(101MHz, CDCl3)δ130.75,128.84,128.25,127.29,77.39,77.08,76.76,11.36.HRMS(EI+)m / z calc'd for C9H 10 N3[M+H] + :160.0870,found160.0880.

[0065] Example 3: Preparation of compound 5a

[0066] In a 100 mL round-bottom flask, potassium carbonate (6.0 mmol) was added to a 2.0 mmol solution of 3a in acetone. The reaction system was heated to 60 °C, and then compound 7 (2.10 mmol) and potassium iodide (0.10 mmol) were added sequentially. After reacting for 36 hours, the mixture was extracted with ethyl acetate. The combined organic phases were washed three times with saturated brine, dried over Na₂SO₄, and the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate as the eluent in a 5:1 ratio to give compound 5a, which was a colorless liquid.

[0067] 1 H NMR(400MHz,Chloroform-d)δ7.89(s,1H),7.81(dt,J=6.6,1.3Hz,2H),7.46–7.38( m,2H),7.37–7.30(m,1H),4.17(t,J=7.1Hz,2H),2.00(s,6H),1.19(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ172.03,147.55,131.01,130.56,128.93,128.86,128.44, 126.07,77.46,77.15,76.83,68.00,61.98,30.82,25.36,14.04.HRMS(EI+)m / z calc'dfor C 14 H 18 N3O2[M+H] + :260.1394,found 260.1397.

[0068] Example 4: Preparation of compound 5b

[0069] In a 100 mL round-bottom flask, potassium carbonate (6.0 mmol) was added to a 2.0 mmol solution of 3b in acetone. The reaction system was heated to 60 °C, and then compound 7 (2.10 mmol) and potassium iodide (0.10 mmol) were added sequentially. After reacting for 36 hours, the mixture was extracted with ethyl acetate. The combined organic phases were washed three times with saturated brine, dried over Na₂SO₄, and the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate as the eluent in a 5:1 ratio to give compound 5b, which was a colorless liquid.

[0070] 1 H NMR(400MHz,Chloroform-d)δ7.89(s,1H),7.81(dt,J=6.6,1.3Hz,2H),7.46–7.38( m,2H),7.37–7.30(m,1H),4.17(t,J=7.1Hz,2H),1.93(s,1H),1.19(t,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ172.03,147.55,131.01,130.56,128.93,128.86,128.44, 126.07,77.46,77.15,76.83,68.00,61.98,30.82,25.36,14.04.HRMS(EI+)m / z calc'dfor C 14 H 18 N3O2[M+H] + :260.1394,found 260.1397.

[0071] Example 5, Preparation of compound 9a

[0072] To a 50 mL flask, 5a (1.0 mmol) and sodium hydroxide (8.0 mmol) were added sequentially to a 2:1 mixture of ethanol and water. The mixture was heated to 50 °C and reacted for two hours. Then, 2 mol / L concentrated hydrochloric acid was added dropwise. The amount added was determined based on the measured pH. When the pH was less than 1, the mixture was extracted with ethyl acetate. The combined organic phases were washed three times with saturated brine, dried over Na2SO4, and the solvent was removed under reduced pressure to obtain a yellow solid product 9a.

[0073] 1 H NMR (400MHz, DMSO-d6) δ13.33(s,1H),8.32(d,J=2.1Hz,1H),7.88(d,J=7.5Hz,2H),7.48(t,J=7.6Hz,2H),7.43–7.35(m,1H),1.91(s,6H). 13C NMR (101MHz, DMSO) δ173.56,147.09,131.81,130.57,129.48,128.95,126.11, 67.90,40.57,40.37,40.16,39.95,39.74,39.53,39.32,25.43.HRMS(EI+)m / z calc'd for C 12 H 12 N3O2[MH]-:230.0935, found 230.0944.

[0074] Example 6, Preparation of compound 9b

[0075] Add 5b (1.0 mmol) and sodium hydroxide (8.0 mmol) sequentially to a 50 mL flask containing a 2:1 mixture of ethanol and water. Heat to 50 °C and react for two hours. Then, add 2 mol / L concentrated hydrochloric acid dropwise. The amount added depends on the measured pH. When the pH is less than 1, extract with ethyl acetate. Combine the organic phases and wash three times with saturated brine. Dry with Na2SO4 and remove the solvent under reduced pressure to obtain a pale yellow solid product 9b.

[0076] 1 H NMR (400MHz, DMSO-d6) δ13,51–13.01(s,1H),7.77–7.63(m,2H),7.50(t,J=7.6Hz,2H),7.41(t,J=7.4Hz,1H),2.46(s,3H),1.86(s,6H). 13 C NMR (101MHz, DMSO) δ173.62,144.36,140.65,131.39,129.32,128.45,127.30,67. 45,40.59,40.38,40.17,39.96,39.76,39.55,39.34,25.41,12.11.HRMS(EI+)m / z calc'dfor C 13 H 14 N3O2[MH]-:244.1091,found 244.1118.

[0077] Example 7, Preparation of compound 11a

[0078] Anhydrous tetrahydrofuran solution 3a (1.0 mmol) was added to a 25 mL Shelenk flask that had been dehydrated in an oven. Then, N-methylmorpholine (2.5 mmol) and isobutyl chloroformate (1.05 mmol) were added dropwise at 0 °C. After reacting for 30 minutes, tetrahydrofuran solution 10a (1.2 mmol) was added dropwise. The mixture was then allowed to rise to room temperature and reacted for 12 hours. The reaction mixture was diluted with water and extracted with dichloromethane. The combined organic phases were washed three times with saturated brine, dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate (1:1) as the eluent to give compound 11a as a white solid.

[0079] 1 H NMR(400MHz,Chloroform-d)δ7.98(s,1H),7.86–7.77(m,2H),7.49–7.42(m,2H),7.42–7.35(m,1H),5.96(d,J =8.7Hz,1H),3.83–3.68(m,2H),3.42(dd,J=10.4,7.1Hz,1H),2.50(s,1H),2.02(d,J=2.3Hz,7H),0.80(s,9H). 13 C NMR (101MHz, CDCl3) δ173.15,148.55,131.63,129.80,129.05,128.94,126.05,77.43 ,77.32,77.12,76.80,69.68,63.13,60.16,33.41,26.71,26.01,25.78.HRMS(EI+)m / z calc'd for C 18 H 27 N4O2[M+H] + :330.2129,found 330.2126.

[0080] Example 8, Preparation of compound 11b

[0081] To a 25 mL Schlenk flask dried in an oven at high temperature, 1.0 mmol of anhydrous tetrahydrofuran solution of 3b was added. Then, N-methylmorpholine (2.5 mmol) and isobutyl chloroformate (1.05 mmol) were added dropwise at 0 °C. After reacting for 30 minutes, 1.2 mmol of tetrahydrofuran solution of 10b was added dropwise. The reaction was then allowed to proceed to room temperature. After 12 hours, the reaction mixture was diluted with water and extracted with dichloromethane. The combined organic phases were washed three times with saturated brine, dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate as the eluent to give compound 11b as a white solid.

[0082] 1 H NMR(400MHz,Chloroform-d)δ7.71–7.66(m,2H),7.49–7.43(m,2H),7.42–7.34(m,2H),7.32–7.29(m,2H),7.17(dd,J=7.9,1.7Hz,2H), 6.77(d,J=7.3Hz,1H),5.00(dt,J=7.3,4.7Hz,1H),3.85(d,J=7.2Hz,1H),3.80(t,J=4.8Hz,2H),2.52(s,3H),2.00(s,3H),1.96(s,3H). 13 C NMR (101MHz, CDCl3) δ172.47,141.81,138.70,130.84,128.89,128.82,128.32,127.86,127.31,126.4 4,77.41,77.29,77.09,76.77,68.94,66.46,58.52,55.87,25.86,25.79,18.48,11.87.HRMS(EI+)m / z calc'd for C 21 H 25 N4O2[M+H] + :365.1973,found 365.1975.

[0083] Example 9, Preparation of compound 1a

[0084] In a 25 mL Shelenk flask dried in an oven at high temperature, 0.5 mmol of anhydrous 1,2-dichloroethane (5 mL) solution of 11a was added under an inert gas atmosphere. Then, p-dimethylaminopyridine (0.1 mmol), p-toluenesulfonyl chloride (1.5 mmol), and triethylamine (4.0 mmol) were added sequentially. The mixture was then heated to 80 °C and reacted for 15 hours. The reaction was then cooled to room temperature, and the solvent was removed under reduced pressure. The mixture was diluted with dichloromethane, and the organic phases were combined and washed three times with saturated brine. After drying with Na2SO4, the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate = 4:1 as the eluent to give compound 1a as a pale yellow solid.

[0085] 1 H NMR(400MHz,Chloroform-d)δ7.87(s,1H),7.83–7.77(m,2H),7.45–7.38(m,2H),7.36–7.3 0(m,1H),4.22–4.06(m,2H),3.92(dd,J=10.1,7.0Hz,1H),2.04–2.01(m,6H),0.90(s,9H). 13 C NMR (101MHz, CDCl3) δ167.27,147.47,130.88,130.65,128.82,128.34,126.03,77 .41,77.09,76.77,75.56,69.61,63.92,34.06,26.38,26.15,25.73.HRMS(EI+)m / z calc'd for C 18 H 25 N4O[M+H] + :313.2023,found 313.2034.[α] 20 D -47.88 (c 1.00, CHCl3).

[0086] Example 10, Preparation of compound 1b

[0087] In a 25 mL Shelenk flask dried in an oven at high temperature, 0.5 mmol of anhydrous 1,2-dichloroethane (5 mL) solution of 11b was added under an inert gas atmosphere. Then, p-dimethylaminopyridine (0.1 mmol), p-toluenesulfonyl chloride (1.5 mmol), and triethylamine (4.0 mmol) were added sequentially. The mixture was then heated to 80 °C and reacted for 15 hours. The reaction was then cooled to room temperature, and the solvent was removed under reduced pressure. The mixture was diluted with dichloromethane, and the organic phases were combined and washed three times with saturated brine. After drying with Na2SO4, the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate = 4:1 as the eluent to give compound 1b as a white solid.

[0088] 1 H NMR(400MHz,Chloroform-d)δ7.78–7.71(m,2H),7.48–7.41(m,2H),7.38–7.26(m,6H),5.26(dd,J=10.1, 7.5Hz, 1H), 4.64 (dd, J=10.2, 8.4Hz, 1H), 4.15 (dd, J=8.5, 7.5Hz, 1H), 2.52 (s, 3H), 2.06 (d, J=2.0Hz, 6H). 13 C NMR (101MHz, CDCl3) δ169.20,144.91,142.22,140.96,131.56,128.79,128.65,127.88,127.75 ,127.31,126.86,77.42,77.10,76.79,75.96,69.72,63.51,26.60,26.03,12.07.HRMS(EI+)m / z calc'd for C 21 H 23 N4O[M+H] + :347.1867,found 347.1875.[α] 20 D -90.92 (c 1.22, CHCl3).

[0089] The synthetic routes for compounds 1c, 1d, and 1e in this invention are as follows:

[0090]

[0091] Example 11, Preparation of Compound 7

[0092] In a 100 mL round-bottom flask, potassium carbonate (6.0 mmol) was added to a 2.0 mmol solution of compound 6 in acetone. The reaction system was heated to 60 °C, and then compound 4 (2.10 mmol) and potassium iodide (0.10 mmol) were added sequentially. After reacting for 36 hours, the mixture was extracted with ethyl acetate. The combined organic phases were washed three times with saturated brine, dried over Na₂SO₄, and the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate as the eluent in a 5:1 ratio to give compound 7, a pale yellow liquid.

[0093] 1 H NMR (400MHz, Chloroform-d) δ4.11(q,J=7.7,7.2Hz,2H),1.85(s,6H),1.14(t,J=7.2Hz,3H). 13 C NMR(101MHz, CDCl3)δ171.01,124.68,77.44,77.12,76.80,69.61,62.33,24.81,13.95.HRMS(EI+)m / z calc'd for C8H 12 Br2N3O2[M+H] + :341.9271,found341.9271.

[0094] Example 12, Preparation of Compound 8

[0095] In a 100 mL Schlenk flask that had been dried in an oven at high temperature, compound 7 (1.5 mmol), phenylboronic acid (4.5 mmol), potassium carbonate (6.0 mmol), and tetraphenylphosphine palladium (0.15 mmol) were added sequentially under an inert gas atmosphere. A mixed solvent of 1,4-dioxane and water (v:v = 3:1, 7.5 mL) was then added. After sealing the flask and reacting at 100 °C for 36 hours, the system was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The combined organic phases were washed three times with saturated brine, dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate = 5:1 as the eluent to give compound 8, which was a colorless liquid.

[0096] 1 H NMR (400MHz, Chloroform-d) δ7.61–7.51(m,4H),7.38–7.30(m,6H),4.20(q,J=7.1Hz,2H),2.02(s,6H),1.22(t,J=7.1Hz,3H). 13C NMR(101MHz, CDCl3)δ172.02,144.36,131.26,128.49,128.41,128.25,68.01,61.91,25.37,14.05.HRMS(EI+)m / z calc'd for C 20 H 22 N3O2[M+H] + :336.1707, found 336.1714.

[0097] Example 13, Preparation of compound 9c

[0098] Add 5b (1.0 mmol) and sodium hydroxide (8.0 mmol) sequentially to a 50 mL flask containing a 2:1 mixture of ethanol and water. Heat to 50 °C and react for two hours. Then, add 2 mol / L concentrated hydrochloric acid dropwise. The amount added depends on the measured pH. When the pH is less than 1, extract with ethyl acetate. Combine the organic phases and wash three times with saturated brine. Dry with Na2SO4 and remove the solvent under reduced pressure to obtain a pale yellow solid product 9c.

[0099] 1 H NMR (400MHz, DMSO-d6) δ13.35(s,1H),7.66–7.10(m,10H),1.92(s,6H). 13 C NMR(101MHz,DMSO)δ173.44,143.87,131.18,129.23,129.01,128.44,68.18,40.63,40.42,40.21,40.00,39.79,39.58,39.37,25.45.HRMS(EI+)m / z calc'dfor C 18 H 16 N3O2[MH] - :306.1248,found 306.1256.

[0100] Example 14, Preparation of compound 11c

[0101] Anhydrous tetrahydrofuran solution of 9c (1.0 mmol) was added to a 25 mL Shelenk flask that had been dehydrated at high temperature in an oven. Then, N-methylmorpholine (2.5 mmol) and isobutyl chloroformate (1.05 mmol) were added dropwise at 0 °C. After reacting for 30 minutes, tetrahydrofuran solution of 10a (1.2 mmol) was added dropwise. The mixture was then allowed to rise to room temperature and reacted for 12 hours. After diluting the reaction mixture with water, it was extracted with dichloromethane. The combined organic phases were washed three times with saturated brine, dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate = 1:1 as the eluent to give compound 11c, a white solid.

[0102] 1 H NMR(400MHz,Chloroform-d)δ7.61–7.48(m,4H),7.42–7.33(m,6H),6.11(d,J=8.6 Hz,1H),3.82–3.70(m,2H),3.46(dd,J=10.8,7.3Hz,1H),2.06(s,6H),0.81(s,9H). 13 C NMR(101MHz, CDCl3)δ173.24,145.37,130.55,128.73,128.33,77.42,77.10,76.78,69.65,63.17,60.19,33.44,26.71,25.98,25.63.HRMS(EI+)m / z calc'd for C 24 H 31 N4O2[M+H] + :407.2442,found 407.2431.

[0103] Example 15, Preparation of compound 11d

[0104] To a 25 mL Shelenk flask dehydrated in an oven at high temperature, add 9c (1.0 mmol) of anhydrous tetrahydrofuran solution. At 0 °C, N-methylmorpholine (2.5 mmol) and isobutyl chloroformate (1.05 mmol) are added dropwise sequentially. After reacting for 30 minutes, 10b (1.2 mmol) of tetrahydrofuran solution is added dropwise. The reaction mixture is then brought to room temperature and allowed to react for 12 hours. After diluting the reaction mixture with water, it is extracted with dichloromethane. The combined organic phases are washed three times with saturated brine, dried over Na2SO4, and the solvent is removed under reduced pressure. The residue is subjected to column chromatography with petroleum ether:ethyl acetate = 1:1 as the eluent to give compound 11d, a white crystalline solid.

[0105] 1H NMR(400MHz,Chloroform-d)δ7.58–7.51(m,4H),7.37(p,J=3.5Hz,6H),7.25(dq,J=4.8,2.7,1.8Hz,3H),7.17(dd, J=7.3,2.3Hz,2H),6.92(d,J=7.2Hz,1H),5.01(dt,J=7.2,4.6Hz,1H),3.85–3.73(m,2H),2.07(s,3H),2.02(s,3H). 13 C NMR (101MHz, CDCl3) δ172.18,145.30,138.71,130.65,128.91,128.69,128.39,127 .87,126.45,77.41,77.10,76.78,69.48,66.48,55.90,25.94,25.78.HRMS(EI+)m / z calc'd for C 26 H 27 N4O2[M+H] + :427.2129,found 427.2124.

[0106] Example 16, Preparation of compound 11e

[0107] Add 9c (1.0 mmol) of anhydrous tetrahydrofuran solution to a 25 mL Shelenk flask that has been dehydrated in an oven at high temperature. Then, add N-methylmorpholine (2.5 mmol) and isobutyl chloroformate (1.05 mmol) dropwise at 0 °C. After reacting for 30 minutes, add 10c (1.2 mmol) of tetrahydrofuran solution dropwise. Then, raise the temperature to room temperature and react for 12 hours. After diluting the reaction system with water, extract with dichloromethane, combine the organic phases, wash three times with saturated brine, dry with Na2SO4, remove the solvent under reduced pressure, and perform column chromatography on the residue with petroleum ether:ethyl acetate = 1:1 as the eluent to give compound 11e, which is a white solid.

[0108] 1 H NMR(400MHz,Chloroform-d)δ7.60–7.50(m,4H),7.44–7.34(m,6H),7.23–7.01(m,7H),6.90(d,J=8.1Hz,1H),6.88 –6.81(m,4H),5.26(dd,J=8.3,4.2Hz,1H),4.93(d,J=4.2Hz,1H),2.86(s,1H),2.03(d,J=2.4Hz,3H),1.96(s,3H). 13C NMR (101MHz, CDCl3) δ171.92,145.21,139.06,137.17,130.70,128.71,128.41,128.23,127.96,127.89 ,127.70,127.43,126.54,77.43,77.12,77.04,76.80,69.46,59.34,25.79,25.69.HRMS(EI+)m / zcalc'd for C 32 H 31 N4O2[M+H] + :503.2442,found 503.2440.

[0109] Example 17, Preparation of compound 1c

[0110] In a 25 mL Shelenk flask dried in an oven at high temperature, 5 mL of anhydrous 1,2-dichloroethane (0.5 mmol) of compound 1c was added under an inert gas atmosphere. Then, p-dimethylaminopyridine (0.1 mmol), p-toluenesulfonyl chloride (1.5 mmol), and triethylamine (4.0 mmol) were added sequentially. The mixture was then heated to 80 °C and reacted for 15 hours. The reaction was then cooled to room temperature, and the solvent was removed under reduced pressure. The mixture was diluted with dichloromethane, and the organic phases were combined and washed three times with saturated brine. After drying with Na2SO4, the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate = 4:1 as the eluent to give compound 1c, which was a white solid.

[0111] 1 H NMR(400MHz,Chloroform-d)δ7.60–7.49(m,4H),7.34(dd,J=5.1,2.0Hz,6H),4.2 4–4.08(m,2H),3.93(dd,J=10.1,7.0Hz,1H),2.04(d,J=2.5Hz,6H),0.93(s,9H). 13 CNMR (101MHz, CDCl3) δ167.30,144.22,131.41,128.46,128.44,128.18,77.39 ,77.07,76.76,75.57,69.61,63.97,34.10,26.50,26.12,25.78.HRMS(EI+)m / z calc'd forC 24 H 29 N4O[M+H] + :389.2336,found 389.2331.[α] 20 D-47.96 (c1.00, CHCl3).

[0112] Example 18, Preparation of compound 1d

[0113] To a 25 mL Shelenk flask dried in an oven at high temperature, 5 mL of anhydrous 1,2-dichloroethane (11d) was added under an inert gas atmosphere. Then, p-dimethylaminopyridine (0.1 mmol), p-toluenesulfonyl chloride (1.5 mmol), and triethylamine (4.0 mmol) were added sequentially. The mixture was then heated to 80 °C and reacted for 15 hours. The reaction was then cooled to room temperature, and the solvent was removed under reduced pressure. The mixture was diluted with dichloromethane, and the organic phases were combined and washed three times with saturated brine. After drying with Na2SO4, the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate = 4:1 as the eluent to give compound 1d as a white solid.

[0114] 1 H NMR (400MHz, Chloroform-d) δ7.68–7.55(m,4H),7.42–7.27(m,11H),5.28(dd,J=10.1,7. 4Hz, 1H), 4.67 (dd, J=10.1, 8.5Hz, 1H), 4.19 (dd, J=8.5, 7.4Hz, 1H), 2.12 (d, J=6.8Hz, 6H). 13 C NMR (101MHz, CDCl3) δ168.97,144.39,142.25,131.30,128.81,128.70,128.54,128.46,128 .31,127.79,126.94,77.41,77.09,76.77,76.05,69.79,64.09,26.81,25.91.HRMS(EI+)m / z calc'd for C 26 H 25 N4O[M+H] + :409.2021,found 409.2023.[α] 20 D -153.16 (c 1.00, CHCl3).

[0115] Example 19, Preparation of compound 1e

[0116] In a 25 mL Shelenk flask dried in an oven at high temperature, 0.5 mmol of anhydrous 1,2-dichloroethane (5 mL) solution was added under an inert gas atmosphere. Then, p-dimethylaminopyridine (0.1 mmol), p-toluenesulfonyl chloride (1.5 mmol), and triethylamine (4.0 mmol) were added sequentially. The mixture was then heated to 80 °C and reacted for 15 hours. The reaction was then cooled to room temperature, and the solvent was removed under reduced pressure. The mixture was diluted with dichloromethane, and the organic phases were combined and washed three times with saturated brine. After drying with Na2SO4, the solvent was removed under reduced pressure. The residue was subjected to column chromatography with petroleum ether:ethyl acetate = 4:1 as the eluent to give compound 1e as a white solid.

[0117] 1 H NMR (400MHz, Chloroform-d) δ7.69–7.62(m,4H),7.45–7.36(m,11H),7.32(s,5H),5.35(d,J=6.8Hz,1H),5.16(d,J=6.8Hz,1H),2.24(d,J=1.4Hz,6H). 13 C NMR (101MHz, CDCl3) δ168.29,144.50,142.03,140.64,131.34,128.99,128.89,128.56,128.49,128.43, 128.35,127.97,126.83,125.59,89.86,78.88,77.44,77.12,76.80,64.32,26.51,26.32.HRMS(EI+)m / z calc'd for C 32 H 29 N4O[M+H] + :485.2336,found485.2340.[α] 20 D -117.80 (c 1.00, CHCl3).

[0118] Example 20: Preparation of compound (R)-3-methyl-3-phenylcyclohexan-1-one by in-situ complexation of compound 1a with palladium trifluoroacetate catalyzing the reaction of arylboronic acid with β-substituted unsaturated cyclic ketones.

[0119]

[0120] In a 10 mL Schlenk flask dried in an oven at high temperature, under an oxygen atmosphere, arylboronic acid (0.50 mmol), compound 1a (0.025 mmol), palladium trifluoroacetate (0.0188 mmol), ytterbium trifluoromethanesulfonate (0.0375 mmol), and 1,2-dichloroethane (1 mL) were added sequentially. After stirring at room temperature for 5 minutes, a β-substituted unsaturated cyclic ketone (0.25 mmol) was added. The temperature was then raised to 60 °C, and the reaction was carried out for 60 hours. After cooling to room temperature and removing the solvent under vacuum, the residue was subjected to column chromatography with petroleum ether:ethyl acetate = 5:1 as the eluent to give the product (R)-3-methyl-3-phenylcyclohexan-1-one. The product was a pale yellow liquid with a yield of 95%, [α-]. 20 D -31.84 (c0.750, CHCl3, -46%ee). HPLC (Daicel Chiralpak OJ-H, n-hexane / 2-propanol=99:1, flow rate=1mL / min, λ=214nm, t major =12.032,t minor =14.137). 1 H NMR(400MHz,Chloroform-d)δ7.36(d,J=4.3Hz,4H),7.27–7.18(m,1H),2.92(d,J=14.2Hz,1H),2.47(d,J=14.2Hz,1H),2.35(t,J =6.8Hz,2H),2.22(dddd,J=13.5,8.0,3.6,1.5Hz,1H),1.93(dddd,J=17.7,10.9,7.8,3.3Hz,2H),1.76–1.60(m,1H),1.36(s,3H). 13 C NMR(101MHz, CDCl3)δ211.70,147.47,128.59,126.26,125.65,77.41,77.30,77.09,76.77,53.14,42.90,40.88,37.99,29.88,22.08.HRMS(EI+)m / z calc'd for C 13 H 17 O[M+H] + :189.1274,found 189.1293.

[0121] Example 21: Preparation of compound (R)-3-(4-fluorobenzyl)-3-phenylcyclohexan-1-one by in-situ complexation of compound 1d with palladium trifluoroacetate catalyzing the reaction of arylboronic acid with β-substituted unsaturated cyclic ketones.

[0122]

[0123] In a 10 mL Schlenk flask dried in an oven at high temperature, under an oxygen atmosphere, arylboronic acid (0.50 mmol), compound 1d (0.0425 mmol), palladium trifluoroacetate (0.0375 mmol), ytterbium trifluoromethanesulfonate (0.0375 mmol), and 1,2-dichloroethane (1 mL) were added sequentially. After stirring at room temperature for 5 minutes, a β-substituted unsaturated cyclic ketone (0.25 mmol) was added. The mixture was then heated to 60 °C, sealed, and reacted for 60 hours. After cooling to room temperature and removing the solvent under vacuum, the residue was subjected to column chromatography with petroleum ether:ethyl acetate = 5:1 as the eluent to give product (R)-3-(4-fluorobenzyl)-3-phenylcyclohexan-1-one. The product was a pale yellow liquid, 60% yield, [α-]. 20 D -18.86 (c0.79, CHCl3, 90%ee). HPLC (Daicel Chiralpak AD-H, n-hexane / 2-propanol=95:5, flowrate=1.00mL / min, λ=214nm, t major =6.533,t minor =7.810). 1 H NMR(400MHz,Chloroform-d)δ7.29(dd,J=8.2,6.7Hz,2H),7.23–7.19(m,1H),7.18–7.12 (m,2H),6.83–6.76(m,2H),6.65–6.57(m,2H),2.95–2.82(m,2H),2.82–2.75(m,1H),2.46 (d,J=14.3Hz,1H),2.35(ddd,J=13.8,5.3,2.7Hz,1H),2.26(dd,J=8.3,5.5Hz,2H),1.99( ddd,J=13.9,11.1,3.5Hz,1H),1.90(ddd,J=13.9,5.5,3.6Hz,1H),1.56(t,J=4.3Hz,1H). 13C NMR (101MHz, CDCl3) δ211.20, 161.68 (d, J = 244.6Hz), 143.80, 132.36 (d, J = 3.03Hz), 131.77 (d, J = 7. 7Hz), 126.53, 114.52 (d, J = 21.0Hz), 77.40, 77.08, 76.76, 50.18, 49.57, 47.36, 40.88, 35.91, 21.50. 19 F NMR(376MHz,CDCl3)δ-116.73.HRMS(EI+)m / z calc'dfor C 19 H 20 FO[M+H] + :283.1493,found 203.1506.

[0124] The above detailed description is a specific illustration of one feasible embodiment of the present invention, and this embodiment is not intended to be limiting. All equivalent implementations or modifications made without departing from the scope of the present invention should be included within the scope of this patent.

Claims

1. A chiral triazole-oxazoline compound, characterized in that, The compound is of high optical purity and is designated as compound 1. Its structural formula is shown below: ； When R 1 For hydrogen, R 2 For tert-butyl, R 3 When it is hydrogen, it is denoted as compound 1a; When R 1 It is a phenyl group, R 2 It is a phenyl group, R 3 When it is hydrogen, it is denoted as compound 1d; The structural formulas of compounds 1a and 1d are as follows: 。 2. A method for preparing the chiral triazole-oxazoline compound according to claim 1, characterized in that, The steps include the following S1, S2, S5, S6, S7 or S3, S4, S5, S6, S7; S1: Under inert gas protection, in an organic solvent, and with the aid of an oxidant, sodium azide reacts with compound 2 at 15–30 °C for 12–36 hours to obtain compound 3; the molar ratio of compound 2, sodium azide, and oxidant is 1:1.5:2; the molar volume ratio of compound 2 to organic solvent is 0.2 mmol:1 mL; wherein, compound 2 is phenylethynyltrimethylsilane, and the oxidant is iodophenyldiacetic acid; S2: Under inert gas protection, in an organic solvent, and in the presence of a base and a catalyst, compound 3 and compound 4 combine and react at 50-70°C for 24-36 hours to obtain compound 5; the molar ratio of compound 3, compound 4, base, and catalyst is 1:1.05:3:0.05, and the molar volume ratio of compound 3 to organic solvent is 0.2 mmol:1 mL; wherein the base is potassium carbonate, the catalyst is potassium iodide, and compound 4 is ethyl 2-bromo-2-methylpropionate; S3: Under inert gas protection, in an organic solvent, and in the presence of a base and a catalyst, compound 6 combines with compound 4 and reacts at 50–70 °C for 24–36 hours to obtain compound 7; the molar ratio of compound 6, compound 4, base, and catalyst is 1:1.05:3:0.05, and the molar volume ratio of compound 6 to organic solvent is 0.2 mmol:1 mL; wherein the base is potassium carbonate, the catalyst is potassium iodide, and compound 6 is 4,5-dibromotriazole; S4: Under inert gas protection, compound 7, a base, and phenylboronic acid are added to a mixed solvent of organic solvent and water. The mixture is reacted at 80-100°C for 24-36 hours in the presence of a palladium catalyst to obtain compound 8. The molar ratio of compound 7, phenylboronic acid, base, and palladium catalyst is 1:3:4:0.1, and the molar volume ratio of compound 7 to the mixed solvent is 0.2 mmol:1 mL. The base is potassium carbonate, and the palladium catalyst is tetrakis(triphenylphosphine)palladium. S5: In a mixed solvent of organic solvent and water, under the action of a strong base, compound 5 or compound 8 undergoes an ester hydrolysis reaction at 20-50°C for 2-12 hours, followed by neutralization with hydrochloric acid to obtain compound 9; the molar ratio of compound 5 or compound 8 to the strong base is 1:8, and the molar volume ratio of compound 5 or 8 to the organic solvent is 1 mmol:1 mL; S6: Under inert gas protection, compound 9, N-methylmorpholine, isobutyl chloroformate, and compound 10 are added sequentially to an organic solvent. Compound 9 and compound 10 undergo an amidation reaction at 0–20 °C for 12–18 hours to obtain compound 11. The molar ratio of compound 9, N-methylmorpholine, isobutyl chloroformate, and compound 10 is 1:1.05:2.5:1.

2. The molar volume ratio of compound 9 to the organic solvent is 0.2 mmol:1 mL. Compound 10 is S-tert-leucine or L-phenylglycine. S7: Under inert gas protection, in an organic solvent, in the presence of p-dimethylaminopyridine, p-toluenesulfonyl chloride and an organic amine, compound 11 undergoes a dehydration condensation reaction at 20–80 °C for 15–30 hours to obtain compound 1, namely the chiral triazole-oxazoline compound; the molar ratio of compound 11, p-dimethylaminopyridine, p-toluenesulfonyl chloride and organic amine is 1:0.2:3:8; the molar volume ratio of compound 11 to organic solvent is 0.1 mmol:1 mL.

3. The method for preparing a chiral triazole-oxazoline compound according to claim 2, characterized in that, The inert gas mentioned in steps S1, S6, and S7 is nitrogen and / or argon; the organic solvent mentioned in step S1 is anhydrous acetonitrile; the organic solvent mentioned in steps S2 and S3 is acetone; the mixed solvent mentioned in step S4 is a mixture of 1,4-dioxane and water in a volume ratio of 3:1; the organic solvent mentioned in step S6 is anhydrous tetrahydrofuran; the organic solvent mentioned in step S7 is 1,2-dichloroethane; and the organic amine mentioned is triethylamine.

4. The method for preparing a chiral triazole-oxazoline compound according to claim 2, characterized in that, The reaction temperature in step S1 is 25°C, and the reaction temperature in step S7 is 80°C.

5. The method for preparing a chiral triazole-oxazoline compound according to claim 2, characterized in that, The strong base in step S5 is sodium hydroxide, the mixed solvent is a mixture of ethanol and water in a volume ratio of 2:1, and the hydrochloric acid is 2 mol / L concentrated hydrochloric acid.

6. An application of the chiral triazole-oxazoline compound according to claim 1, wherein a chiral organic compound is prepared by in-situ complexation of the chiral triazole-oxazoline compound and a palladium salt compound to generate a catalyst, followed by asymmetric addition of arylboronic acid to the carbon-carbon double bond of the pre-chiral organic compound. The specific steps are as follows: under an oxygen atmosphere, arylboronic acid, compound 1, palladium trifluoroacetate, Lewis acid, and organic solvent are added sequentially. After stirring at room temperature for 5 minutes, a β-substituted unsaturated cyclic ketone is added, followed by heating at 20-80°C and sealing the tube for 12-60 hours to obtain the chiral product; wherein the Lewis acid is ytterbium trifluoromethanesulfonate.

7. The application of a chiral triazole-oxazoline compound according to claim 6, characterized in that, The compound 1 is compound 1a or 1d, and the molar ratio of the β-substituted unsaturated cyclic ketone, arylboronic acid, compound 1a or 1d, palladium trifluoroacetate, and Lewis acid is 1:2:0.1:0.075:0.15 or 1:2:0.17:0.15:0.15; the molar volume ratio of the β-substituted unsaturated cyclic ketone to the organic solvent is 0.25 mmol:1 mL.

8. The application of a chiral triazole-oxazoline compound according to claim 6, characterized in that, The organic solvent is 1,2-dichloroethane.

9. The application of a chiral triazole-oxazoline compound according to claim 6, characterized in that, The reaction temperature for the sealing reaction is 60 or 40°C, and the reaction time is 60 hours.

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