Preparation method and application of a tridentate chiral ligand of binaphthyl imidazoline

Abstract

The present invention discloses a preparation method and application of a novel binaphthyl imidazoline tridentate chiral ligand. The ligand is synthesized from a chiral binaphthyl intermediate and proline as starting materials. On the one hand, the spatial structure of the ligand can be adjusted by changing the chirality of each chiral center. On the other hand, different R<supgt;1< / supgt>, R<supgt;2< / supgt>, R<supgt;3< / supgt> and R<supgt;4< / supgt> substituents can be introduced to optimize the steric and electronic properties of the ligand. It is a potential chiral ligand with both high efficiency and universality. The metal complex formed in situ by this type of ligand and a metal copper precursor can catalyze the asymmetric addition reaction of coumarin, pyrone and β,γ-unsaturated ketone ester under mild conditions, and the yield and enantioselectivity of the reaction can reach up to 99%.

Description

Technical Field

[0001] The invention relates to a chiral binaphthyl-imidazoline ligand.

[0002] The invention also relates to a method for preparing the binaphthyl-imidazoline ligand.

[0003] The present invention also relates to the application of the above-mentioned binaphthyl-imidazoline ligand in the asymmetric addition reaction of coumarin, pyrone and β, γ-unsaturated ketoester catalyzed by metallic copper. Background Art

[0004] Metal-catalyzed asymmetric reactions have become an important strategy for the preparation of chiral compounds, and the design and synthesis of chiral ligands are the key to achieving this strategy. As a classic class of chiral ligands, bisoxazoline ligands (BOX) have been widely used in various asymmetric catalytic reactions. As a structural analogue of oxazoline, imidazoline, in addition to having a similar advantageous spatial conformation to oxazoline in structure, can also adjust the electronic effect, as well as the basicity and nucleophilicity of the coordinated atom N by introducing different substituents on the N atom. Therefore, the introduction of the imidazoline module provides more space for ligand modification and is a powerful alternative to the oxazoline module. For some reactions where oxazoline ligands perform poorly, the use of imidazoline ligands is a very good strategy, which is more conducive to breaking through the bottleneck in the current asymmetric catalysis field.

[0005] In recent years, although imidazoline ligands have made great progress, the effect of N-substituents in this group on catalysts has been largely unexplored, and the development of new asymmetric catalytic reactions using these catalysts is also very urgent. Therefore, the development of new imidazoline ligands and in-depth study of the mechanism of action of N-substituents on imidazoline ligands are of great significance for solving some long-standing problems in the current asymmetric catalysis field and developing new asymmetric reactions. Summary of the invention

[0006] The object of the present invention is to provide a tridentate chiral ligand of binaphthyl imidazoline. Another object of the present invention is to provide a method for preparing the above ligand.

[0007] The chiral ligand provided by the present invention has the following structural formula:

[0008]

[0009] Without showing the chiral elements in the ligand, the above 16 structures can be summarized as follows:

[0010]

[0011] Where: R 1 is one of hydrogen, fluorine, chlorine, bromine, iodine and trifluoromethyl; R2 is one of arylsulfonyl groups such as 4-methylbenzenesulfonyl, 2-nitrobenzenesulfonyl, 3-nitrobenzenesulfonyl, 4-nitrobenzenesulfonyl, and benzenesulfonyl; R 3 is one of hydrogen, isopropyl, tert-butyl, and phenyl, R 4 It is one of hydrogen and phenyl.

[0012] The chiral binaphthyl-imidazoline ligand L of the present invention has the following synthesis route:

[0013]

[0014] The specific synthesis steps are:

[0015] Step (1)

[0016] In molar ratio I:II:K 2 CO 3 The above compound was added to an appropriate volume of acetonitrile and reacted at room temperature for 12 hours. After the reaction, the compound III was obtained by separation and purification.

[0017] Step (2)

[0018] Compound III and KOH (molar ratio of 1:1.5) were added to an appropriate amount of methanol and reacted at 60°C for 4 hours. After the reaction was completed, compound IV was obtained by separation and purification.

[0019] Step (3)

[0020] At 0℃, Tf 2 O and O=PPh 3 Dissolve in an appropriate amount of dry DCM and react for 1 hour. A large amount of white precipitate is generated in the system. Compound IV is added thereto and the reaction is continued for 2 hours. After the reaction is completed, ligand L is obtained by separation and purification. 2 O:O=PPh 3 The molar ratio of IV is 2:4:1.

[0021] Wherein, compound II in step (1) is prepared by the following method:

[0022]

[0023] Where R 2 is one of arylsulfonyl groups such as 4-methylbenzenesulfonyl, 2-nitrobenzenesulfonyl, 3-nitrobenzenesulfonyl, 4-nitrobenzenesulfonyl, and benzenesulfonyl; R 3 is one of hydrogen, isopropyl, tert-butyl, and phenyl, R 4 It is one of hydrogen and phenyl. The specific steps are:

[0024] Step (a)

[0025] Boc-protected proline, ethylenediamine compounds, EDCI, HOBt and Et 3 N (molar ratio of 1:1.2:1.5:1.5:3) was dissolved in an appropriate amount of dry DCM and reacted at room temperature for 24 hours. After the reaction was completed, compound V was obtained by separation and purification.

[0026] Step (b)

[0027] Compound V was dissolved in an appropriate amount of dry DCM, TFA was added, and the reaction was carried out for 6 hours. After the reaction was completed, compound II was obtained by separation and purification, wherein the molar ratio of V:TFA was 1:10.

[0028] The ethylenediamine compound used in step (a) of the preparation method is a monoarylsulfonyl-protected ethylenediamine.

[0029] The asymmetric addition reaction of coumarin, pyrone and β,γ-unsaturated ketoester catalyzed by the chiral binaphthyl-imidazoline ligand-metal copper complex provided by the present invention can obtain 99% enantioselectivity.

[0030] The beneficial effects of the present invention are:

[0031] The catalyst formed in situ by the chiral binaphthyl-imidazoline ligand and metal designed and synthesized by the present invention has a wide range of applications and can be applied to a variety of asymmetric catalytic reactions, wherein the metal copper complex of the ligand can obtain 99% enantioselectivity in the asymmetric addition reaction of coumarin, pyrone and β,γ-unsaturated ketoester.

[0032] The chiral binaphthyl-imidazoline ligand designed by the present invention is stable in nature, easy to store, has a simple synthesis route and mild reaction conditions. The metal copper complex of the ligand can obtain 99% enantioselectivity in the asymmetric addition reaction of coumarin, pyrone and β,γ-unsaturated ketoester, has high catalytic activity and a wide range of substrate applications, and is a high-quality ligand with both high efficiency and universality. In addition, by introducing different substituents at the C-3 position of the binaphthyl ring of the ligand and the N atom of imidazoline, the electronic properties and spatial conformation of the ligand can be further adjusted and optimized, and applied to more substrates and more reaction types. In the design process of this ligand, we have deeply studied the influence of the N atom substituent on the imidazoline unit on the properties of the ligand, which provides a certain guiding role for the research of other imidazoline ligands. Using this chiral ligand, a variety of important chiral molecular intermediates can be synthesized through asymmetric catalytic reactions, providing greater value for the development of industries such as medicine, materials, and food. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is the H NMR spectrum of the ligand L-1 obtained in Example 1.

[0034] Figure 2 This is the NMR carbon spectrum of the ligand L-1 obtained in Example 1. DETAILED DESCRIPTION

[0035] (I) Synthesis of ligands

[0036] Example 1

[0037] Preparation of ligand L1

[0038] Synthetic intermediate II-1

[0039]

[0040] Step (a)

[0041] Boc-L-proline (3.4 g), (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide (6.0 g), EDCI (4.8 g), HOBt (3.2 g) and Et 3 N (7 mL) was dissolved in 100 mL of dry DCM and reacted at room temperature for 24 hours. After the reaction, the mixture was washed with water and saturated brine, concentrated, and purified by column chromatography to obtain compound V-1 (6.4 g, 85%).

[0042] Step (b)

[0043] Compound V-1 (6.0 g) was dissolved in 30 mL of dry DCM, TFA (20 mL) was added, and the mixture was reacted for 6 hours. After the reaction, the reaction solution was slowly poured into an ice-cold saturated sodium bicarbonate solution, then extracted with DCM, washed with saturated brine, the organic phase was collected, dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure, and separated by column chromatography to obtain the target compound II-1 (3.8 g, 80%).

[0044] Synthetic ligand L-1

[0045]

[0046] Compound 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate (I-1) (2.2 g) and compound II-1 (2.0 g) were dissolved in 50 mL of acetonitrile, and K 2 CO 3 (1.37 g), sodium iodide (180 mg), react at room temperature for 12 hours. After TLC detection, add 50 mL of ethyl acetate to dilute the reaction solution, wash with water, wash with saturated brine, collect the upper organic phase, dry over anhydrous magnesium sulfate, distill under reduced pressure to remove the solvent, and obtain white solid product III-1 (2.3 g, 75%) by petroleum ether and ethyl acetate column chromatography.

[0047] Compound III-1 (1.8 g) and KOH (210 mg) were dissolved in 30 mL of methanol and reacted at 60° C. for 4 hours. After TLC detected that the reaction was complete, the reaction solution was removed by distillation under reduced pressure, 50 mL of ethyl acetate was added, washed with water, washed with saturated brine, the upper organic phase was collected, dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The white solid product IV-1 (1.4 g, 85%) was obtained by column chromatography with petroleum ether and ethyl acetate.

[0048] At 0℃, Tf 2 O (2.6 g) and O=PPh 3 (5.2g) was dissolved in 30mL dry DCM and reacted for 1 hour. A large amount of white precipitate was generated in the system. Compound IV-1 (1.3g) was added thereto and the reaction was continued for 2 hours. After the reaction was completed, a saturated sodium bicarbonate solution was added to adjust the pH value to neutral, and then washed with water and saturated brine. The organic phase was collected and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and a white solid product L1 (910mg, 70%) was obtained by column chromatography with petroleum ether and ethyl acetate. White solid, mp198-200℃; [α] D 20 = +27.66 (c = 0.98 in DCM). 1 H NMR (400 MHz, CDCl 3 )δ10.88(s,1H),8.05(s,1H),7.89-7.66(m,3H),7.51(d,J=8.0Hz,2H),7.38(t,J=7.4Hz,1H),7.29(t,J=7 .5Hz,1H),7.24(d,J=8.4Hz,1H),7.18(t,J=7.6Hz,1H),7.09(t,J=8.3Hz,2H),6.99(d,J=7.8Hz,2H),6.61 (d,J=8.5Hz,1H),4.27(d,J=7.9Hz,1H),3.66-3.51(m,4H),3.09(t,J=7.5Hz,1H),2.76-2.62(m,1H),2.55 (q,J=8.0Hz,1H),2.48-2.29(m,4H),1.97-1.88(m,1H),1.88-1.78(m,1H),1.77-1.68(m,1H),0.24(s,9H). 13 CNMR (100MHz, CDCl 3)δ159.7,150.8,144.7,137.2,135.0,134.0,134.0,133.6,132.9,130 .0,128.9,128.6,128.5,127.9,127.4,127.3,127.0,126.7,126.5,12 6.3,125.9,125.1,123.9,122.6,73.6,62.7,59.0,54.2,49.2,33.0,3 2.7,29.8,25.5,23.3,21.6.IR(KBr):υ=3055,2924,1642,1161,755cm -1 .IR(KBr):υ=3053,2962,1645,1164,756cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 39 H 41 C1N 3 O 3 S 666.2552, measured value: 666.2557.

[0049] Example 2

[0050] Preparation of ligand L2

[0051]

[0052] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced with (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-benzenesulfonamide, and finally ligand L2 (72% yield) was prepared. White solid, mp115-117℃; [α] D 20 = +29.41 (c = 0.75 in DCM); 1 H NMR (400 MHz, CDCl 3)δ10.54(s,1H),7.88(s,1H),7.63(d,J=8.2Hz,1H),7.60(d,J=8.1Hz,1H),7.54(t,J=8.3Hz,3H),7.40(t, J=7.5Hz,1H),7.23-7.19(m,1H),7.18-7.10(m,3H),7.09-7.05(m,1H),7.03-6.98(m,1H),6.95-6.89(m,2H ),6.43(d,J=8.5Hz,1H),4.11-4.05(m,1H),3.48-3.37(m,4H),2.94(t,J=8.2Hz,1H),2.50-2.41(m,1H),2 .39-2.31(m,1H),2.29-2.19(m,1H),1.81-1.73(m,1H),1.69-1.60(m,1H),1.57-1.50(m,1H),0.01(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ160.0,150.6,137.9,137.4,133.9,133.9,133.7,133.5,132.7,129.5,128.6,128.5,127.8,127.4,127.2,127.1,126.7,126.6,126 .5,126.3,125.8,124.9,123.9,122.4,73.5,63.0,59.3,54.6,49.2,33.0,32.9,25.3,23.4.IR(KBr):υ=3055,2954,1643,1163,750cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 38 H 39 C1N 3 O 3 S 652.2395, measured value: 652.2398.

[0053] Example 3

[0054] Preparation of ligand L3

[0055]

[0056] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced with (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-2-nitrobenzenesulfonamide to finally obtain ligand L3 (68% yield). White solid, mp91-93℃; [α] D 20 = -1.55 (c = 0.40 in DCM); 1 H NMR (400 MHz, CDCl 3 )δ10.51(s,1H),8.02(s,1H),7.93(d,J=7.9Hz,1H),7.83(t,J=8.2Hz,2H),7.78-7.67(m,3H ),7.62-7.50(m,2H),7.41-7.34(m,1H),7.31-7.24(m,1H),7.21-7.15(m,1H),7.12-7.03(m ,2H),6.61(d,J=8.5Hz,1H),4.12(d,J=8.8Hz,1H),3.76-3.57(m,4H),3.41-3.23(m,1H),2. 56-2.35(m,2H),2.20-2.05(m,1H),1.84-1.69(m,2H),1.63(d,J=10.7Hz,1H),0.25(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ160.2,150.5,148.3,137.9,134.7,134.0,133.8,133.6,132.7,132 .3,131.8,131.0,128.9,128.6,128.5,127.9,127.7,127.2,126.5,126 .4,126.3,125.8,125.0,124.9,123.9,122.6,73.6,63.0,59.1,55.1, 49.5,33.2,32.8,25.3,23.5.IR(KBr):υ=3056,2924,1649,1163,733cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 38 H 38 C1N 4 O 5 S 697.2246, measured value: 697.2248.

[0057] Example 4

[0058] Preparation of ligand L4

[0059]

[0060] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced with (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-3-nitrobenzenesulfonamide to finally obtain ligand L4 (59% yield). White solid, mp103-105℃; [α] D 20 = +18.73 (c = 0.20 in DCM); 1 H NMR (400 MHz, CDCl 3 )δ10.23(s,1H),8.53(s,1H),8.24(d,J=8.1Hz,1H),7.85(s,1H),7.68(d,J=7.6Hz,1H),7.64-7.57(m, 2H),7.54(d,J=8.2Hz,1H),7.18(dt,J=13.8,7.7Hz,3H),7.12-7.06(m,1H),7.00(t,J=7.4Hz,1H),6.90 (d,J=7.9Hz,2H),6.40(d,J=8.4Hz,1H),4.07(d,J=9.4Hz,1H),3.43(d,J=7.2Hz,3H),2.99(d,J=15.0H z,1H),2.48(s,1H),2.40-2.30(m,1H),2.28-2.16(m,1H),1.76-1.60(m,2H),1.55(s,1H),0.01(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ159.3,148.3,140.2,137.3,133.9,133.8,133.5,132.6,132.4,131.0,128.8,128.6,128.5,128.0,127.8,127.1,126.9,126 .4,126.4,125.9,124.8,124.0,122.5,73.6,62.9,59.4,54.8,49.3,32.9,25.2,23.4.IR(KBr):υ=3055,2955,1645,1166,752cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 38 H 38 C1N 4 O5 S 697.2246, measured value: 697.2246.

[0061] Example 5

[0062] Preparation of ligand L5

[0063]

[0064] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced with (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-nitrobenzenesulfonamide to finally obtain ligand L5 (68% yield). White solid, mp101-103℃; [α] D 20 = -5.93 (c = 0.30 in DCM); 1 H NMR (400 MHz, CDCl 3 )δ10.61(s,1H),7.99(s,1H),7.86-7.69(m,5H),7.58(d,J=8.4Hz,2H),7.38 -7.25(m,3H),7.16-7.05(m,2H),6.99(d,J=8.5Hz,1H),6.59(d,J=8.4Hz,1H ),4.25(d,J=8.7Hz,1H),3.66-3.45(m,4H),3.05-2.94(m,1H),2.86-2.74(m ,1H),2.65-2.54(m,1H),2.45-2.31(m,1H),1.90-1.68(m,3H),0.25(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ157.9,150.5,150.3,143.3,136.5,133.9,133.8,133.6,132.7,129.0,128.9,128.7,128.5,128.0,127.3,127.0,126.7,126.7,126 .7,126.1,125.2,124.6,124.5,123.0,73.9,62.2,58.6,53.2,49.0,33.1,32.1,25.4,23.0.IR(KBr):υ=2952,2923,1645,1161,738cm - 1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 38 H 38C1N 4 O 5 S 697.2246, measured value: 697.2248.

[0065] Example 6

[0066] Preparation of ligand L6

[0067]

[0068] Referring to the method in Example 1, the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced by N-(2-aminoethyl)-4-methylbenzenesulfonamide, and the raw material 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate was replaced by 2'-bromomethyl-[1,1'-binaphthyl]-2-yl acetate, and finally ligand L6 (48% yield) was prepared. White solid, mp95-97℃; [α] D 20 = +247.42 (c = 0.30 in DCM); 1 H NMR (400 MHz, CDCl 3 )δ10.49(s,1H),7.84-7.71(m,4H),7.67(d,J=8.2Hz,1H),7.42-7.32(m,3H),7.25(d,J=8.9 Hz,2H),7.12(dd,J=12.9,7.4Hz,3H),6.98(t,J=7.7Hz,1H),6.60(dd,J=15.7,8.4Hz,2H),3 .76-3.67(m,1H),3.63(d,J=12.1Hz,1H),3.55-3.44(m,1H),3.27(q,J=9.6Hz,1H),3.00(dd ,J=13.5,8.5Hz,2H),2.42(s,4H),2.25-2.13(m,2H),2.00-1.88(m,1H),1.70-1.47(m,3H). 13 C NMR (100 MHz, CDCl 3)δ163.1,155.1,145.2,138.2,136.4,135.2,133.9,133.7,133.0,130.2,129.4,128.6,127.9,127.5,127.3,127.3,127.0,126.4, 126.1,125.8,124.0,122.5,120.8,118.2,61.9,59.2,56.0,50.4,48.5,33.1,23.6,21.8.IR(KBr):υ=3052,2955,1647,1163,750cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 35 H 34 N 3 O 3 S 576.2315, measured value: 576.2318.

[0069] Example 7

[0070] Preparation of ligand L7

[0071]

[0072] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced with (S)-N-(2-amino-3-methyl-tert-butyl)-4-methylbenzenesulfonamide, and the raw material 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate was replaced with 2'-bromomethyl-[1,1'-binaphthyl]-2-yl acetate, and finally ligand L7 (61% yield) was prepared. White solid, mp172-174℃; [α] D 20 = +134.17 (c = 0.80 in DCM); 1 H NMR (400 MHz, CDCl 3)δ9.96(s,1H),7.93-7.78(m,4H),7.75(d,J=8.2Hz,1H),7.49-7.30(m,5H),7.26-7.18(m,1H),7.15( d,J=3.7Hz,2H),7.05(t,J=7.3Hz,1H),6.63(d,J=8.4Hz,1H),6.50(d,J=8.3Hz,1H),3.99-3.82(m,1H ),3.79-3.57(m,2H),3.23-2.98(m,2H),2.99-2.83(m,1H),2.60-2.42(m,4H),2.39-2.24(m,2H),1.8 6-1.70(m,2H),1.68-1.53(m,1H),0.27(d,J=6.7Hz,3H),0.15(d,J=6.4Hz,3H),-0.05--0.30(m,1H). 13 C NMR (100 MHz, CDCl 3 )δ161.8,154.8,145.1,138.2,136.1,134.8,134.3,134.0,133.4,130. 2,129.5,128.7,128.0,127.7,127.4,127.4,127.0,126.8,126.2,126.1 ,125.7,124.4,122.7,121.1,118.8,70.1,62.7,59.6,56.1,53.0,33.6 ,32.7,23.7,21.8,19.5,18.7.IR(KBr):υ=3054,2962,1646,1163,755cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 38 H 40 N 3 O 3 S 618.2785, measured value: 618.2788.

[0073] Example 8

[0074] Preparation of ligand L8

[0075]

[0076] Referring to the method in Example 1, only the raw material 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate was replaced with 2'-bromomethyl-[1,1'-binaphthyl]-2-yl acetate, and finally ligand L8 (53% yield) was prepared. White solid, mp114-116℃; [α]D 20 = -35.26 (c = 0.70 in DCM); 1 H NMR (400 MHz, CDCl 3 )δ7.95(d,J=8.9Hz,1H),7.90(d,J=8.1Hz,1H),7.85(d,J=8.2Hz,1H),7.75(d,J=8.3Hz,1H),7.55(d,J=8.3Hz,3H ),7.43-7.38(m,1H),7.35-7.29(m,2H),7.22-7.13(m,3H),6.99(d,J=7.8Hz,2H),6.74(d,J=8.4Hz,1H),4.36(d, J=8.3Hz,1H),3.65(d,J=9.8Hz,3H),3.57(t,J=9.6Hz,1H),3.12(t,J=9.0Hz,1H),2.88-2.80(m,1H),2.59(q,J=7 .9Hz,1H),2.47-2.40(m,1H),2.37(s,3H),2.02-1.95(m,1H),1.90-1.81(m,1H),1.77-1.70(m,1H),0.29(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ159.7,154.3,144.7,137.3,134.8,134.2,134.1,133.5,130.0,129 .7,129.1,128.2,128.1,127.8,127.3,127.2,126.7,126.2,126.2,12 5.6,125.0,123.0,121.6,120.3,73.6,62.6,58.8,54.0,49.2,32.8,3 2.7,27.0,25.4,23.2,21.5.IR(KBr):υ=3054,2955,1644,1161,750cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 39 H 42 N 3 O 3 S632.2941, measured value: 632.2948.

[0077] Example 9

[0078] Preparation of ligand L9

[0079]

[0080] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced by (1S,2S)-N-(2-amino-1,2-diphenyl)-4-methylbenzenesulfonamide, and the raw material 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate was replaced by 2'-bromomethyl-[1,1'-binaphthyl]-2-yl acetate, and finally ligand L9 (53% yield) was prepared. White solid, mp118-120℃; [α] D 20 = -62.68 (c = 0.56 in DCM); 1 H NMR (400 MHz, CDCl 3 )δ7.94-7.90(m,2H),7.87(d,J=8.2Hz,2H),7.69-7.64(m,1H),7.51(d,J=8.5Hz,2H),7.47-7.42(m,2H),7.32(t,J=8.4Hz,4H), 7.16(t,J=9.2Hz,6H),7.09(d,J=8.5Hz,1H),6.97-6.92(m,1H),6.77(d,J=8.4Hz,1H),6.63(t,J=6.5Hz,4H),6.11(d,J=7.6Hz, 2H),4.80(d,J=5.5Hz,1H),4.65(d,J=8.8Hz,1H),4.60(d,J=5.6Hz,1H),3.84(d,J=12.4Hz,1H),3.72(d,J=12.5Hz,1H),2.91(d ,J=9.5Hz,1H),2.69-2.60(m,1H),2.41-2.31(m,1H),2.25(s,3H),2.07(d,J=8.1Hz,1H),1.97-1.88(m,1H),1.82-1.76(m,1H). 13 CNMR (100MHz, CDCl 3)δ161.9,154.2,144.5,141.9,140.5,135.2,134.2,133.9,133.4,132.2,132.1 ,129.8,129.2,129.0,128.6,128.5,128.2,128.2,128.1,128.1,127.6,127.3, 127.1,126.9,126.4,126.4,126.2,125.7,125.6,125.1,123.0,121.8,71.9,62 .9,58.5,53.6,32.3,26.9,23.3,21.4.IR(KBr):υ=3055,2924,1642,1161,751cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 47 H 42 N 3 O 3 S 728.2941, measured value: 728.2947.

[0081] Example 10

[0082] Preparation of ligand L10

[0083]

[0084] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced by (1R,2R)-N-(2-amino-1,2-diphenyl)-4-methylbenzenesulfonamide, and the raw material 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate was replaced by 2'-bromomethyl-[1,1'-binaphthyl]-2-yl acetate, and finally ligand L10 (53% yield) was prepared. White solid, mp106-108℃; [α] D 20 = +126.44 (c = 0.60 in DCM); 1 H NMR (400 MHz, CDCl 3)δ10.07(s,1H),7.80-7.69(m,3H),7.60(d,J=8.3Hz,1H),7.33-7.25(m,2H),7.20-7.13(m,3H),7.12-7.03(m,9H), 7.00(t,J=7.6Hz,1H),6.90(d,J=8.1Hz,2H),6.76(d,J=7.4Hz,2H),6.62(dd,J=6.0,3.0Hz,2H),6.56(d,J=8.5Hz,1 H),4.65(d,J=7.8Hz,1H),4.12(d,J=7.7Hz,1H),3.85(d,J=7.7Hz,1H),3.74(d,J=12.4Hz,1H),3.38(d,J=12.4Hz,1 H),2.58(t,J=7.8Hz,1H),2.54-2.37(m,2H),2.27(s,3H),2.08-1.97(m,1H),1.96-1.85(m,1H),1.71-1.62(m,1H). 13 C NMR (100 MHz, CDCl 3 )δ163.3,154.8,144.3,140.9,138.9,137.9,136.6,135.0,134.1,133.9,133.1 ,129.5,129.4,128.9,128.7,128.4,128.1,128.1,128.0,127.7,127.6,127.6, 127.3,126.8,126.5,126.1,126.0,125.9,124.5,122.8,121.6,119.4,76.1,72 .9,62.8,59.0,55.2,34.3,23.8,21.6.IR(KBr):υ=3052,2923,1643,1160,750cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 47 H 42 N 3 O 3 S728.2941, measured value: 728.2949.

[0085] Embodiment 11

[0086] Preparation of ligand L11

[0087]

[0088] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced by (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-3-nitrobenzenesulfonamide, and the raw material 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate was replaced by 2'-bromomethyl-3-fluoro-[1,1'-binaphthyl]-2-yl acetate, and finally ligand L11 (55% yield) was prepared. White solid, mp105-107℃; [α] D 20 = +13.60 (c = 0.90 in DCM); 1 HNMR (400MHz, CDCl 3 )δ8.75(s,1H),8.51(d,J=8.1Hz,1H),8.03(d,J=7.7Hz,1H),7.78(d,J=8.0Hz,2H),7.68(d,J=8.1Hz,1H),7.65 -7.50(m,2H),7.38(t,J=7.4Hz,1H),7.31-7.25(m,2H),7.19(t,J=7.3Hz,1H),7.12-7.01(m,2H),6.56(d,J=8.2 Hz,1H),4.24(d,J=9.8Hz,1H),3.65(t,J=11.1Hz,1H),3.61-3.54(m,2H),3.16(t,J=7.5Hz,1H),2.77-2.54(m,1 H),2.54-2.43(m,1H),2.43-2.31(m,1H),1.90-1.83(m,1H),1.82-1.73(m,1H),1.72-1.65(m,1H),0.08(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ159.3,147.4,132.4,131.6,129.9,129.5,127.6,127.0,126.7,126.2,125.6,125.5,125.3, 124.8,124.3,123.6,123.0,121.6,110.8,72.4,62.3,59.0,54.8,48.4,32.4,31.7,24.0,22.6. 19 F NMR (CDCl 3 )δ-131.8.IR(KBr):υ=3285,2960,1657,1165,732cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C38 H 38 FN 4 O 5 S 681.2541, measured value: 681.2545.

[0089] Example 12

[0090] Preparation of ligand L12

[0091]

[0092] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced by (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-3-nitrobenzenesulfonamide, and the raw material 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate was replaced by 2'-bromomethyl-3-bromo-[1,1'-binaphthyl]-2-yl acetate, and finally ligand L12 (59% yield) was prepared. White solid, mp99-101℃; [α] D 20 = +30.22 (c = 0.30 in DCM); 1 HNMR (400MHz, CDCl 3 )δ10.54(s,1H),8.69(s,1H),8.37(d,J=8.1Hz,1H),8.24(s,1H),7.84-7.71(m,4H),7.42-7. 33(m,2H),7.32-7.27(m,1H),7.25-7.17(m,2H),7.13-7.04(m,2H),6.60(d,J=8.5Hz,1H),4. 25(d,J=9.3Hz,1H),3.63(s,2H),3.61(d,J=11.1Hz,2H),3.16(d,J=14.6Hz,1H),2.71(s,1H) ,2.57(t,J=7.6Hz,1H),2.46-2.36(m,1H),1.94-1.80(m,2H),1.79-1.71(m,1H),0.25(s,9H). 13 C NMR (100 MHz, CDCl 3)δ158.8,150.9,148.3,140.2,137.0,133.9,133.8,133.5,133.2,132 .3,132.0,130.9,129.4,128.6,127.9,127.8,127.0,127.0,126.5,126 .5,125.9,125.0,124.0,122.5,122.1,116.8,73.7,62.6,59.0,54.2, 49.2,33.0,32.6,25.3,23.2.IR(KBr):υ=3431,2955,1647,1167,751cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 38 H 38 Bn 4 O 5 S 741.1741, measured value: 741.1745.

[0093] Example 13

[0094] Preparation of ligand L13

[0095]

[0096] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced by (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-3-nitrobenzenesulfonamide, and the raw material 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate was replaced by 2'-bromomethyl-3-iodo-[1,1'-binaphthyl]-2-yl acetate, and finally ligand L13 (61% yield) was prepared. White solid, mp96-98℃; [α] D 20 = +21.87 (c = 0.50 in DCM); 1 HNMR (400MHz, CDCl 3)δ10.98(s,1H),8.67(s,1H),8.52(s,1H),8.32(d,J=8.1Hz,1H),7.81(d,J=8.1Hz,1H),7.75(d,J=7.9Hz,2H),7.6 6(d,J=7.5Hz,1H),7.41-7.34(m,2H),7.32-7.26(m,1H),7.18(t,J=7.5Hz,1H),7.13(t,J=7.5Hz,1H),7.05(d,J=8 .0Hz,2H),6.63(d,J=8.5Hz,1H),4.27(d,J=8.9Hz,1H),3.71-3.61(m,3H),3.56(d,J=12.8Hz,1H),3.15(d,J=15.2 Hz,1H),2.80(s,1H),2.69-2.58(m,1H),2.50-2.39(m,1H),1.96-1.85(m,2H),1.77(d,J=17.0Hz,1H),0.32(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ158.1,152.6,148.2,140.1,139.0,136.5,134.2,134.0,133.7,133 .5,132.2,131.0,130.3,128.5,127.8,127.1,126.9,126.7,126.6,12 6.5,125.9,125.1,123.8,122.5,120.9,93.3,73.8,62.2,58.6,53.4, 49.1,33.0,32.2,25.4,23.1.IR(KBr):υ=3434,2955,1648,1167,756cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 38 H 38 IN 4 O 5 S 789.1602, measured value: 789.1606.

[0097] Embodiment 14

[0098] Preparation of ligand L14

[0099]

[0100] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced with N-(2-aminoethyl)-4-methylbenzenesulfonamide to finally obtain ligand L14 (67% yield). White solid, mp198-200℃; [α] D 20 = +204.21 (c = 0.80 in DCM); 1 HNMR (400MHz, CDCl 3 )δ11.61(s,1H),7.99(s,1H),7.87(d,J=7.9Hz,2H),7.74(dd,J=14.2,8.2Hz,2H),7.47(t,J=9.0Hz,3H) ,7.41-7.34(m,1H),7.26-7.19(m,3H),7.05(t,J=7.7Hz,1H),6.66(d,J=8.5Hz,1H),6.59(d,J=8.3Hz,1H ),3.75(dd,J=10.3,4.5Hz,1H),3.67(d,J=12.3Hz,1H),3.58(q,J=9.7Hz,1H),3.37(q,J=9.7Hz,1H),3.1 4-2.98(m,2H),2.53(s,3H),2.38-2.18(m,3H),1.97-1.86(m,1H),1.83-1.67(m,2H),1.65-1.57(m,1H). 13 C NMR (100 MHz, CDCl 3 )δ163.4,151.2,145.3,138.4,136.3,134.7,133.3,133.0,132.5,130.2,128.3,128.1,127.6,127.3,127.3,127.1,127.1,126.6,126.2, 126.2,125.9,125.5,124.0,123.4,120.1,61.9,59.2,56.2,50.0,48.5,33.1,29.8,23.8,21.8.IR(KBr):υ=3051,2925,1645,1163,748cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 35 H 33 C1N 3 O 3 S 610.1926, measured value: 610.1928.

[0101] Embodiment 15

[0102] Preparation of ligand L15

[0103]

[0104] Referring to the method in Example 1, only the raw material (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-4-methylbenzenesulfonamide was replaced by (S)-N-(2-amino-3,3-dimethyl-tert-butyl)-3-nitrobenzenesulfonamide, and the raw material 2'-bromomethyl-3-chloro-[1,1'-binaphthyl]-2-yl acetate was replaced by 2'-bromomethyl-3-trifluoromethyl-[1,1'-binaphthyl]-2-yl acetate, and finally ligand L15 (51% yield) was prepared. White solid, mp94-96℃; [α] D 20 = +0.99 (c = 0.60 in DCM); 1 H NMR (400 MHz, CDCl 3 )δ10.83(s,1H),8.66(d,J=2.1Hz,1H),8.35(d,J=8.4Hz,1H),8.26(s,1H),7.92(d,J=8.2Hz ,1H),7.85-7.71(m,3H),7.44-7.31(m,3H),7.20(q,J=8.0Hz,3H),7.01(d,J=8.5Hz,1H),6. 65(d,J=8.6Hz,1H),4.33(d,J=9.3Hz,1H),3.68-3.52(m,4H),3.18(d,J=14.7Hz,1H),2.83( q,J=6.9,6.4Hz,1H),2.66-2.53(m,1H),2.42-2.28(m,1H),1.89-1.69(m,3H),0.31(s,9H). 13 C NMR (100 MHz, CDCl 3 )δ158.5,151.7,148.4,140.4,136.9,135.7,134.0,133.7,133.6,132.3,131.0,129.2,128.7,128.4,δ128.2(q, 3 J C-F =5.5Hz),128.0,127.9,127.3,127.2,126.7,126.6,126.0,125.6,125.0,124.22(q, 1 J C-F =272.6Hz),124.2,123.0,122.5,122.4(q, 2 JC-F =29.4Hz),73.9,62.2,59.0,53.9,49.3,33.1,32.3,25.4,23.0. 19 F NMR (CDCl 3 )δ-62.5.IR(KBr):υ=3437,2957,1648,1129,731cm -1 .HRMS-ESI(m / z):[M+H] + Calculated value: C 39 H 38 F 3 N 4 O 5 S 731.2510, measured value: 731.2512.

[0105] (ii) Application of binaphthyl-imidazoline ligands in the asymmetric addition reaction of coumarins, pyrones and β,γ-unsaturated ketoesters catalyzed by metallic copper.

[0106] Application Example 1

[0107] Asymmetric Addition of Coumarin to β,γ-Unsaturated Ketoesters

[0108]

[0109] L-1 (7.5% mol) and CuOTf (7.5% mol) were dissolved in 2 mL of dry dichloromethane at room temperature and stirred for 1 hour; β,γ-unsaturated ketoester (1 equivalent) was added thereto and stirred for 0.5 hour, followed by coumarin (1.1 equivalent) and reacted for 12 hours. After the reaction, the reaction solvent was removed by vacuum distillation, the target product was obtained by column chromatography, and then the enantioselectivity was obtained by HPLC. (The yield can reach up to 99%, and the ee value can reach up to 99%)

[0110] Application Example 2

[0111] Asymmetric Addition of Pyrones to β,γ-Unsaturated Ketoesters

[0112]

[0113] L-1 (7.5% mol) and CuOTf (7.5% mol) were dissolved in 2 mL of dry dichloromethane at room temperature and stirred for 1 hour; β,γ-unsaturated ketoester (1 equivalent) was added thereto, stirred for 0.5 hour, and then pyrone (1.1 equivalent) was added and reacted for 12 hours. After the reaction was completed, the reaction solvent was removed by vacuum distillation, and the target product was obtained by column chromatography, and then the enantioselectivity was obtained by HPLC. (The yield can reach up to 99%, and the ee value can reach up to 99%)

[0114] The above embodiments describe the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for illustrating the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. A tridentate chiral ligand of binaphthyl imidazoline, It is characterized in that Its structural formula is selected from: Without showing the chiral elements in the ligand, the above 16 structures can be summarized as follows: Where: R 1 is one of hydrogen, fluorine, chlorine, bromine, iodine or trifluoromethyl; R 2 is one of 4-methylbenzenesulfonyl, 2-nitrobenzenesulfonyl, 3-nitrobenzenesulfonyl, 4-nitrobenzenesulfonyl or benzenesulfonyl; R 3 is one of hydrogen, isopropyl, tert-butyl or phenyl, R 4 It is one of hydrogen or phenyl.

2. The method for preparing the tridentate chiral ligand of binaphthyl imidazoline according to claim 1, It is characterized in that The synthetic route is: Where: R 1 is one of hydrogen, fluorine, chlorine, bromine, iodine and trifluoromethyl; R 2 is one of 4-methylbenzenesulfonyl, 2-nitrobenzenesulfonyl, 3-nitrobenzenesulfonyl, 4-nitrobenzenesulfonyl and benzenesulfonyl; R 3 is one of hydrogen, isopropyl, tert-butyl, and phenyl, R 4 is one of hydrogen and phenyl; The synthesis steps are: Step (1) Compound I, compound II, K 2 CO 3 and NaI in a molar ratio of 1:1.2:2:0.1 were added to an appropriate volume of acetonitrile, and the mixture was reacted at room temperature for 12 hours. After the reaction was completed, compound III was obtained by separation and purification; Step (2) Compound III and KOH were added to an appropriate amount of methanol at a molar ratio of 1:1.5, and reacted at 60°C for 4 hours. After the reaction, compound IV was obtained by separation and purification; Step (3) At 0 °C, Tf 2 O and triphenylphosphine oxide were dissolved in an appropriate amount of dry DCM, and the reaction was carried out for 1 hour. A large amount of white precipitate was formed in the system. Compound IV was added thereto, and the reaction was continued for 2 hours; after the reaction was completed, the ligand L was obtained by separation and purification; wherein Tf 2 The molar ratio of O, triphenylphosphine oxide and compound IV is 2:4:

1.

3. The preparation method according to claim 2, It is characterized in that In step (1), compound II is prepared by the following method: Where: R 2 is one of 4-methylbenzenesulfonyl, 2-nitrobenzenesulfonyl, 3-nitrobenzenesulfonyl, 4-nitrobenzenesulfonyl and benzenesulfonyl; R 3 is one of hydrogen, isopropyl, tert-butyl, and phenyl, R 4 is one of hydrogen and phenyl; the specific steps are: Step (a) Boc protected proline, compound EDCI, HOBt and Et 3 N was dissolved in an appropriate amount of dry DCM according to a molar ratio of 1:1.2:1.5:1.5:3, and reacted at room temperature for 24 hours. After the reaction, compound V was obtained by separation and purification; Step (b) Compound V was dissolved in an appropriate amount of dry DCM, TFA was added, and the reaction was carried out for 6 hours. After the reaction was completed, compound II was obtained by separation and purification. The molar ratio of V:TFA was 1:

10.

4. Use of the tridentate chiral ligand of binaphthyl imidazoline as claimed in claim 1 in the copper-catalyzed asymmetric addition reaction of coumarin and β,γ-unsaturated ketoester.

5. Use of the binaphthyl imidazoline tridentate chiral ligand as claimed in claim 1 in the copper-catalyzed asymmetric addition reaction of pyrone and β,γ-unsaturated ketoester.

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