Chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligands and their applications in Michael addition reactions

Abstract

The present invention discloses a chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand and its application in Michael addition reactions, belonging to the field of asymmetric catalysis technology in organic chemistry. Using trans-3-substituted-L-prolinamide and pyridine-2,6-dicarboxaldehyde as raw materials, a chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand is obtained through a one-step condensation. Using a Lewis acid and the ligand as catalysts, the asymmetric Michael addition reaction of 4-hydroxycoumarin with β,γ-unsaturated α-ketoesters, at dosages as low as 0.05%, achieves high yields and excellent enantioselectivity. The present invention features a novel ligand structure, a simple synthesis method, and extremely low catalyst usage.

Description

Technical Field

[0001] The invention relates to a chiral pyridine-pyrroloimidazolidinone tridentate nitrogen ligand and application thereof in Michael addition reaction, belonging to the technical field of asymmetric catalysis in organic chemistry. Background Art

[0002] The asymmetric conjugate addition of 1,3-dicarbonyl compounds to various Michael acceptors is an important method for preparing chiral compounds. Over the past two decades, literature has reported on the asymmetric conjugate addition of 4-hydroxycoumarin to β,γ-unsaturated α-ketoesters, achieving excellent results using both metal complex catalysis and small organic molecules.

[0003] However, the catalyst loading range in the existing catalytic system is 2-10 mol%, and the catalyst dosage is high. In order to be more green and environmentally friendly, it is very necessary to develop more efficient catalysts. The asymmetric conjugate addition reaction of 4-hydroxycoumarin and β,γ-unsaturated α-ketoester using a lower catalyst loading has not been reported so far.

[0004] At the same time, various defects still exist in the actual use of catalysts, mainly manifested in the need for expensive reagents and multiple transformations in catalyst synthesis, poor enantioselectivity in catalytic applications, and low catalyst activity. Therefore, it is necessary to find more effective chiral catalysts to further solve the above problems. Summary of the Invention

[0005] To overcome these technical limitations, the present invention provides a novel chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand. Using trans-3-hydroxy-L-prolinamide and pyridine-2,6-dicarboxaldehyde as raw materials, a high-yield chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand is obtained through a one-step condensation. This ligand is then used in the asymmetric conjugate addition reaction of 4-hydroxycoumarin with β,γ-unsaturated α-ketoesters to obtain Michael addition products in high yields and excellent enantioselectivity.

[0006] The present invention is achieved through the following technical solution: a chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand having the general structural formula:

[0007]

[0008] Wherein: n=0-4; R is C1-C8 alkyl, diphenylmethyl, substituted phenyl or substituted naphthyl, and the substitution is one or more of hydrogen, C1-C8 alkyl, C1-C8 alkoxy, trifluoromethyl, nitro, nitrile, halogen, trifluoromethyl; R' is hydrogen, halogen, C1-C8 alkoxy, benzyloxy, hydroxyl, sulfonate, azido, C1-C4 alkoxysilyl, C1-C4 alkanoyloxy or C1-C4 alkanoylthio.

[0009] Furthermore, in the above technical solution, n=1,2; R is C1-C8 alkyl, phenyl, trifluoromethylphenyl, diphenylmethylphenyl; R' is hydroxyl, hydrogen, methoxy, benzyloxy, methanesulfonate, fluorine, acetylthio, azido, trimethylsilyloxy or dimethyl-tert-butylsilyloxy.

[0010] Furthermore, in the above technical solution, in the preferred case, the specific structure is:

[0011]

[0012] The present invention also provides the use of the chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand in the Michael addition reaction of 4-hydroxycoumarin and β,γ-unsaturated α-keto acid ester.

[0013] Furthermore, in the above technical solution, the application includes the following steps: using 4-hydroxycoumarin and β,γ-unsaturated α-keto acid ester as raw materials, reacting in an organic solvent in the presence of a Lewis acid catalyst and a chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand to obtain a Michael addition product; the reaction equation is as follows:

[0014]

[0015] Where: R 1 is selected from phenyl, substituted phenyl, substituted thienyl, wherein the substitution is one or more of hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, trifluoromethyl, nitro, and nitrile; R 2 Selected from C1-C4 alkyl.

[0016] Furthermore, in the above technical solution, the Lewis acid catalyst is Cu(OTf)2, Cu(ClO4)2·6H2O, Ni(OTf)2 or Co(ClO4)2·6H2O.

[0017] Furthermore, in the above technical solution, the molar ratio of the tridentate nitrogen ligand to 4-hydroxycoumarin is 0.005-0.0005:1.

[0018] Furthermore, in the above technical solution, the organic solvent is dichloromethane or tetrahydrofuran; and the reaction temperature is 0-30°C.

[0019] The present invention further provides a method for synthesizing the above-mentioned chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand, comprising the following steps: using trans-3-substituted-L-prolinamide and pyridine-2,6-dicarboxaldehyde as raw materials, and performing a one-step condensation to obtain a chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand.

[0020] Beneficial effects of the invention:

[0021] The present invention provides a novel chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand with a rich structure and strong adjustability. The catalyst is readily available, simple to synthesize, inexpensive, and highly efficient. It exhibits high catalytic activity and, in the asymmetric conjugate addition reaction of 4-hydroxycoumarin with β,γ-unsaturated α-ketoesters, produces Michael addition products in high yields and excellent enantioselectivity. The product stereoselectivity is high, with yields reaching up to 99% and enantioselectivities reaching up to 97%. DETAILED DESCRIPTION

[0022] Example 1

[0023] Synthesis of 2,6-Diisopropylaniline-Substituted Chiral Pyridine-Pyrroloimidazolinone Tridentate Nitrogen Ligands

[0024]

[0025] In a 15 mL pressure tube, 2,6-pyridinedicarboxaldehyde (2.0 mmol, 0.270 g) and 2,6-diisopropyl-derivatized trans-3-hydroxy-L-prolinamide (6.0 mmol, 3.0 eq, 1.740 g) were added, followed by anhydrous ethanol (10 mL). The mixture was heated and stirred in an 80°C oil bath for 12 h, then cooled to room temperature. Thin-layer chromatography (TLC) confirmed complete reaction of the 2,6-pyridinedicarboxaldehyde. The reaction mixture was concentrated in vacuo to remove the ethanol, yielding the crude product. Column chromatography on silica gel using petroleum ether / ethyl acetate (5 / 1-2 / 1) as the eluent afforded a white solid. Recrystallization from ethyl acetate afforded 1.198 g of the product in an 88% yield and >99% ee. HPLCCHIRALPAKIC, n-hexane / 2-propanol=70 / 30, flow rate=0.8mL / min, λ=256nm, retention time: 25.58min (major).

[0026] 1HNMR (400MHz, CDCl3) δ7.64(t,J=8.0Hz,1H),7.41(d,J=7.6Hz,2H),7.21(t,J=7.6 Hz,2H),7.08(d,J=6.0Hz,2H),6.92(d,J=8.0Hz,2H),4.89(s,2H),4.59-4.52(m,4 H),3.30(d,J=10.8Hz,2H),3.00(dd,J=10.8,4.4Hz,2H),2.82-2.75(m,2H),2.39- 2.19(m,8H),1.14(d,J=6.8Hz,12H),0.99(d,J=6.8Hz,6H),0.14(d,J=6.4Hz,6H). 13 CNMR (150MHz, CDCl3) δ174.6,157.9,148.0,146.2,137.6,129.7,129.0,124.1, 123.8,121.9,87.0,72.2,63.8,63.6,38.0,29.0,28.8,25.0,24.9,23.7,22.8.

[0027] Example 2

[0028] Synthesis of 2,6-Diethylaniline-Substituted Chiral Pyridine-Pyrroloimidazolinone Tridentate Nitrogen Ligands

[0029]

[0030] In a 15 mL pressure tube, add 2,6-pyridinedicarboxaldehyde (2.0 mmol, 0.270 g) and 2,6-diethyl-derivatized trans-3-hydroxy-L-prolinamide (6.0 mmol, 3.0 eq, 1.573 g). Anhydrous ethanol (10 mL) was then added. Heat and stir in an 80°C oil bath for 8 hours, then cool to room temperature. Thin-layer chromatography (TLC) confirmed complete reaction of the 2,6-pyridinedicarboxaldehyde. The reaction mixture was concentrated in vacuo to remove the ethanol, yielding the crude product. Column chromatography on a silica gel column using petroleum ether / ethyl acetate (5 / 1-2 / 1) as the eluent afforded 0.998 g of the product as a white solid in 80% yield.

[0031] 1HNMR (600MHz, CDCl3) δ7.65(t,J=7.8Hz,1H),7.46(d,J=7.8Hz,2H),7.17(t,J=7.8Hz,2H) ,7.03(d,J=7.2Hz,2H),6.89(d,J=6.6Hz,2H),4.84(s,2H),4.56(s,2H),4.38(t,J=7.2Hz, 2H),3.32(d,J=10.8Hz,2H),2.99(dd,J=10.8,4.2Hz,2H),2.45-2.38(m,2H),2.35-2.30( m,7H),1.88-1.82(m,2H),1.30-1.24(m,3H),1.15(t,J=7.8Hz,6H),0.67(t,J=7.2Hz,6H). 13 CNMR(150MHz,CDCl3)δ173.6,156.8,142.9,141.3,137.8,131.8,128.4,1 26.3,125.7,120.7,84.6,72.2,63.4,63.1,37.7,24.6,23.0,14.7,13.7.

[0032] Example 3

[0033] Synthesis of Aniline-Substituted Chiral Pyridine-Pyrroloimidazolinone Tridentate Nitrogen Ligands

[0034]

[0035] To a 15 mL pressure tube, add 2,6-pyridinedicarboxaldehyde (2.0 mmol, 0.270 g) and aniline-derived trans-3-hydroxy-L-prolinamide (6.0 mmol, 3.0 eq, 1.237 g). Anhydrous ethanol (10 mL) was then added. The mixture was heated and stirred in an 80°C oil bath for 8 hours, then cooled to room temperature. Thin-layer chromatography (TLC) confirmed complete reaction of the 2,6-pyridinedicarboxaldehyde. The reaction mixture was concentrated in vacuo to remove the ethanol, yielding the crude product. Column chromatography on a silica gel column using petroleum ether / ethyl acetate (5 / 1-2 / 1) as the eluent afforded 0.940 g of the product as a white solid in a 92% yield.

[0036] 1HNMR (600MHz, CDCl3) δ7.64(t,J=7.8Hz,1H),7.36(d,J=7.8Hz,4H),7.20-7.18(m,6H),7.06(t,J=7.2Hz,2H),5.67(s,2H),4.34(s,2 H),4.22(q,J=4.8Hz,2H),3.42(d,J=10.2Hz,2H),3.33(br,2H),2.92(dd,J=10.2,4.2Hz,2H),2.37-2.33(m,2H),2.08-2.04(m,2H). 13 CNMR (150MHz, CDCl3) δ174.9,157.8,138.8,137.3,129.2,125.4,121.2,121.1,83.5,71.5,63.4,63.2,37.1.

[0037] Example 4

[0038] Synthesis of 3,5-Bistrifluoromethylaniline-substituted Chiral Pyridine-Pyrroloimidazolinone Tridentate Nitrogen Ligands

[0039]

[0040] In a 15 mL pressure tube, 2,6-pyridinedicarboxaldehyde (2.0 mmol, 0.270 g) and 3,5-bis(trifluoromethyl)-derivatized trans-3-hydroxy-L-prolinamide (6.0 mmol, 3.0 eq, 2.052 g) were added, followed by anhydrous ethanol (10 mL). The mixture was heated and stirred in an 80°C oil bath for 10 h, then cooled to room temperature. Thin-layer chromatography (TLC) confirmed complete reaction of the 2,6-pyridinedicarboxaldehyde. The reaction mixture was concentrated in vacuo to remove the ethanol and obtain the crude product. Column chromatography on a silica gel column using petroleum ether / ethyl acetate (5 / 1-2 / 1) as the eluent yielded a white solid. Recrystallization from ethyl acetate afforded 0.894 g of the product in a 57% yield. 1 HNMR(600MHz, CDCl3)δ8.00(s,4H),7.83(t,J=7.8Hz,1H),7.57(s,2H),7.41(d,J=7.8Hz,2H),5.77(s,2H),4.50-4.42(m,2H),3.95 (q,J=4.8Hz,2H),3.44(d,J=10.2Hz,2H),2.93(dd,J=10.2,4.2Hz,2H),2.45-2.41(m,2H),2.23-2.16(m,2H),1.89(d,J=6.6Hz,2H). 13CNMR(150MHz,CDCl3)δ175.1,156.8,139.5,139.3,132.5(q,J C-F =33.0Hz),123.0(q,J C-F =273.0Hz),121.9,119.3,118.2,82.3,71.6,63.0,62.9,37.3.

[0041] Example 5

[0042] Synthesis of Diphenylmethylamine-Substituted Chiral Pyridine-Pyrroloimidazolinone Tridentate Nitrogen Ligands

[0043]

[0044] In a 15 mL pressure tube, 2,6-pyridinedicarboxaldehyde (2.0 mmol, 0.270 g) and trans-3-hydroxy-L-prolinamide (6.0 mmol, 3.0 eq, 1.776 g) derived from diphenylmethylamine were added, followed by anhydrous ethanol (10 mL). The mixture was heated and stirred in an 80°C oil bath for 8 h, then cooled to room temperature. Thin-layer chromatography (TLC) confirmed complete reaction of the 2,6-pyridinedicarboxaldehyde. The reaction mixture was concentrated under vacuum to remove the anhydrous ethanol to obtain the crude product. Column chromatography on a silica gel column using petroleum ether / ethyl acetate (5 / 1-2 / 1) as the eluent afforded a white solid. Recrystallization from ethyl acetate afforded 1.14 g of the product in an 82% yield. 1 HNMR(600MHz, (CD3)2SO)δ7.30(t,J=7.8Hz,4H),7.25-7.21(m,3H),7.07(d,J=7.2 Hz,4H),7.05-7.02(m,6H),6.96-6.95(m,4H),6.63(d,J=7.8Hz,2H),5.72(s,2H),5 .14(s,2H),4.92(d,J=3.6Hz,2H),4.27-4.25(m,2H),4.20(q,J=4.8Hz,2H),3.16(d d,J=10.8,3.6Hz,2H),2.94(q,J=5.4Hz,2H),2.09-2.06(m,2H),1.93-1.89(m,2H). 13 CNMR(150MHz,(CD3)2SO)δ175.2,158.4,140.4,138.5,137.1,129.1,128. 3,128.0,127.6,127.1,127.0,120.4,82.7,69.5,63.2,63.0,60.6,36.8.

[0045] Example 6

[0046] Synthesis of 2,6-Diisopropylaniline-Substituted Chiral Pyridine-Pyrroloimidazolinone Tridentate Nitrogen Ligands

[0047]

[0048] To a 15 mL pressure tube, add 2,6-pyridinedicarboxaldehyde (2.0 mmol, 0.270 g) and 2,6-diisopropyl-derivatized L-prolinamide (6.0 mmol, 3.0 eq, 1.644 g). Anhydrous ethanol (10 mL) was then added. The mixture was heated and stirred in an 80°C oil bath for 8 h, then cooled to room temperature. Thin-layer chromatography (TLC) confirmed complete reaction of the 2,6-pyridinedicarboxaldehyde. The reaction mixture was concentrated under vacuum to remove the ethanol, yielding the crude product. Column chromatography on a silica gel column using petroleum ether / ethyl acetate (5 / 1-2 / 1) as the eluent afforded a white solid. Recrystallization from ethyl acetate afforded 0.988 g of the product in a 76% yield. 1 HNMR (600MHz, CDCl3) δ7.61(t,J=7.8Hz,1H),7.36(d,J=7.8Hz,2H),7.21(t,J=7.2Hz,2H),7. 09(dd,J=7.2,1.2Hz,2H),6.92(dd,J=7.8,1.2Hz,2H),4.90(s,2H),4.34(dd,J=8.4,4.8Hz,2H ),3.28-3.24(m,2H),2.89-2.84(m,4H),2.35-2.24(m,4H),2.17-2.11(m,2H),1.93-1.84(m,4 H),1.18(d,J=6.6Hz,6H),1.16(d,J=6.6Hz,6H),0.99(d,J=7.2Hz,6H),0.14(d,J=6.6Hz,6H). 13 CNMR (150MHz, CDCl3) δ174.8,158.4,148.1,146.3,137.4,130.3,128.8,124.0, 123.8,121.6,87.4,65.4,57.1,29.5,29.0,28.8,25.6,25.0,24.9,23.7,22.8.

[0049] Example 7

[0050] Synthesis of 2,6-Diisopropylaniline-Substituted Chiral Pyridine-Pyrroloimidazolinone Tridentate Nitrogen Ligands

[0051]

[0052] To a 15 mL pressure tube, add 2,6-pyridinedicarboxaldehyde (2.0 mmol, 0.270 g) and 2,6-diisopropyl-derivatized L-prolinamide (6.0 mmol, 3.0 eq, 1.824 g). Anhydrous ethanol (10 mL) was then added. The mixture was heated and stirred in an 80°C oil bath for 8 h before cooling to room temperature. Thin-layer chromatography (TLC) confirmed complete reaction of the 2,6-pyridinedicarboxaldehyde. The reaction mixture was concentrated under vacuum to remove the ethanol and obtain the crude product. Column chromatography on a silica gel column using petroleum ether / ethyl acetate (5 / 1-2 / 1) as the eluent afforded a white solid. Recrystallization from ethyl acetate afforded 1.276 g of the product in a 90% yield. 1 HNMR (600MHz, CDCl3) δ7.68(t,J=7.8Hz,1H),7.53(d,J=7.8Hz,2H),7.20(t,J=7.8Hz,2H),7.07(dd,J=7. 8,1.2Hz,2H),6.91(dd,J=7.8,1.2Hz,2H),4.80(s,2H),4.42(t,J=6.6Hz,2H),4.10-4.07(m,2H),3.37(s, 6H),3.32(dd,J=10.2,3.0Hz,2H),2.92(q,J=5.4Hz,2H),2.76(sept,J=6.6Hz,2H),2.43-2.38(m,2H),2.2 5-2.18(m,4H),1.15(d,J=7.2Hz,6H),1.12(d,J=7.2Hz,6H),0.97(d,J=6.6Hz,6H),0.16(d,J=6.6Hz,6H). 13 CNMR (150MHz, CDCl3) δ174.0,157.7,148.0,146.2,137.8,130.0,128.9,123.9,12 3.8,121.8,87.5,80.9,64.0,61.1,57.2,34.5,29.1,28.8,25.0,24.8,23.8,22.7.

[0053] Example 8

[0054] Synthesis of 2,6-Diisopropylaniline-Substituted Chiral Pyridine-Pyrroloimidazolinone Tridentate Nitrogen Ligands

[0055]

[0056] In a 15 mL pressure tube, 2,6-pyridinedicarboxaldehyde (20.0 mmol, 2.702 g) and 2,6-diisopropyl-derivatized trans-hydroxy-L-prolinamide (60.0 mmol, 3.0 eq, 17.40 g) were added, followed by anhydrous ethanol (80 mL). The mixture was heated and stirred in an 80°C oil bath for 12 h, then cooled to room temperature. Thin-layer chromatography (TLC) confirmed complete reaction of the starting 2,6-pyridinedicarboxaldehyde. The reaction solution was then concentrated under vacuum to remove the anhydrous ethanol to obtain the crude product. Column chromatography on a silica gel column using petroleum ether / ethyl acetate (5 / 1-2 / 1) as the eluent afforded a white solid. Further recrystallization from ethyl acetate afforded 10.6 g of the product in a 78% yield and >99% ee.

[0057] Example 9

[0058] To a reaction tube, a Lewis acid (1 mol%), a chiral ligand (1 mol%), and 1 mL of THF were added for dissolution, and the THF was removed under vacuum. β,γ-unsaturated α-ketoester 2a (20.9 mg, 0.11 mmol) and dichloromethane (1.0 mL) were then added, and the reaction was stirred at 25°C for 0.5 h. 4-Hydroxycoumarin 1a (16.2 mg, 0.1 mmol) was then added at 25°C, and the reaction was stirred at 25°C until 4-Hydroxycoumarin 1a disappeared (TLC). Purification by flash column chromatography (Et / EtOAc = 5 / 1 to 2 / 1) afforded the corresponding product 3a as a white solid. 1 H NMR (600 MHz, CDCl 3 ): δ 7.86-7.80 (m, 1H), 7.59-7.53 (m, 1H), 7.38-7.23 (m, 7H), 4.96 (s, 0.66H), 4.63 (s, 0.30H), 4.35 (dd, J = 7.8, 3.6 Hz, 0.32H), 4.22 (t, J = 9.0 Hz, 0.71H), 3.93 (s, 1H), 3.86 (s, 2H), 2.81 (dd, J = 14.4, 7.8 Hz, 0.32H), 2.55 (dd, J = 14.4, 3.6 Hz, 0.33H), 2.48 (d, J = 9.0 Hz, 1.39H). The experimental results are as follows:

[0059]

[0060]

[0061]

[0062] Example 10

[0063] Based on the optimization of Example 9, the amount of catalyst and ligand was further screened.

[0064] In a 25.0 mL volumetric flask, add Co(ClO4)2·6H2O (4.6 mg, 0.0125 mmol), then add THF to make the total volume to 25.0 mL; in a 25.0 mL volumetric flask, add L1 (8.5 mg, 0.0125 mmol), then add THF to make the total volume to 25.0 mL.

[0065] To a reaction tube, 100 μL of Co(ClO₄)₂·6H₂O (0.05 mol%) and 100 μL of L1 (0.05 mol%) were added, and the THF was removed under vacuum. β,γ-unsaturated α-ketoester 2a (20.9 mg, 0.11 mmol) and dichloromethane (1.0 mL) were added, and the reaction was stirred at 25°C for 0.5 h. 4-Hydroxycoumarin 1a (16.2 mg, 0.1 mmol) was then added and the reaction was stirred at 25°C until the 4-hydroxycoumarin 1a disappeared (TLC). Purification by flash column chromatography (Et / EtOAc = 5 / 1 to 2 / 1) afforded 34.5 mg of product 3a as a white solid in 98% yield and 96% ee.

[0066]

[0067] Example 11

[0068]

[0069]

[0070] a Unless otherwise specified, the reaction steps are as follows: substrate concentration (0.1 mmol), solvent volume (1.0 mL), b Separation yield c The ee values were separated by high performance liquid chromatography.

[0071] Example 12

[0072]

[0073] To a reaction tube, 100 μL of Co(ClO₄)₂·6H₂O (0.05 mol%) and 100 μL of L1 (0.05 mol%) were added, and the THF was removed under vacuum. β,γ-unsaturated α-ketoester 2a (20.9 mg, 0.11 mmol) and dichloromethane (1.0 mL) were added, and the reaction was stirred at 25°C for 0.5 h. 4-hydroxy-6-methyl-2-pyrone (12.6 mg, 0.1 mmol) was then added and the reaction was stirred at 25°C until the 4-hydroxy-6-methyl-2-pyrone was completely consumed (as determined by thin-layer chromatography). The corresponding product was directly purified by flash column chromatography (Et / EtOAc = 5 / 1-2 / 1) to give 28.6 mg of a white solid in 91% yield and 93% ee. 1 HNMR (600MHz, CDCl3): δ7.31-7.27(m,2H),7.23-7.19(m,3H),5.88(d,J=1.2Hz,0.29H ),5.81(d,J=0.6Hz,0.67H),4.71(s,0.67H),4.39(d,J=1.8Hz,0.30H),4.17(q,J=3.6 Hz,0.31H),4.04(t,J=9.0Hz,0.72H),3.87(s,1H),3.79(s,2H),2.69-2.65(m,0.32H) ,2.44(dd,J=13.8,3.0Hz,0.34H),2.33(d,J=8.4Hz,1.43H),2.25(s,1H),2.21(s,2H).

[0074] Example 13

[0075]

[0076] To a reaction tube, 500 μL of Co(ClO₄)₂·6H₂O (0.05 mol%) and 500 μL of L1 (0.05 mol%) were added, and the THF was removed under vacuum. β,γ-unsaturated α-ketoester 2a (19.0 mg, 0.1 mmol) and dichloromethane (1.0 mL) were added, and the reaction was stirred at 25°C for 0.5 h. 1,3-cyclohexanedione (12.3 mg, 0.11 mmol) was then added and the reaction was stirred at 25°C until the 1,3-cyclohexanedione was completely consumed (as determined by thin-layer chromatography). Finally, the corresponding product was directly purified by flash column chromatography (Et / EtOAc = 5 / 1-2 / 1), yielding 26.3 mg of a white solid in 87% yield and 96% ee.

[0077] 1HNMR (600MHz, CDCl3): δ7.27-7.24(m,2H),7.17-7.15(m,3H),4.72(s,0.68H),4.31(s,0.38H),4.10-4.09(m,0.3 5H), 3.90 (t, J = 8.4Hz, 0.69H), 3.84 (s, 1H), 3.74 (s, 2H), 2.63-2.34 (m, 4H), 2.29-2.22 (m, 2H), 2.11-1.99 (m, 2H).

[0078] The above embodiments illustrate 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 merely illustrative of the principles of the present invention. Various changes and improvements may be made to the present invention without departing from the scope of the principles of the present invention, and all such changes and improvements fall within the scope of protection of the present invention.

Claims

1. A chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand, characterized in that: Its chemical structure is:

2. Use of the chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand according to claim 1 in the Michael addition reaction of 4-hydroxycoumarin and β,γ-unsaturated α-keto acid ester, characterized in that: The steps include: Using 4-hydroxycoumarin and β,γ-unsaturated α-ketoester as raw materials, in the presence of Lewis acid catalyst and chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand L1 or L2, the reaction is carried out in an organic solvent to obtain a Michael addition product; wherein: R 1 is selected from phenyl, substituted phenyl, substituted thienyl, wherein the substitution is one or more of hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, trifluoromethyl, and nitrile; R 2 Selected from C1-C4 alkyl.

3. The use according to claim 2, characterized in that: The Lewis acid catalyst is Cu(ClO4)2·6H2O, Co(ClO4)2·6H2O, Cu(OTf)2 or Ni(OTf)2.

4. The use according to claim 2, characterized in that: The molar ratio of the tridentate nitrogen ligand to 4-hydroxycoumarin is 0.005-0.0005:

1.

5. The use according to claim 2, characterized in that: The organic solvent is dichloromethane or tetrahydrofuran; the reaction temperature is 0-30°C.

6. The method for preparing a chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand according to claim 1, wherein: The steps include: Using trans-3-hydroxy-L-prolinamide and pyridine-2,6-dicarboxaldehyde as raw materials, a chiral pyridine-pyrroloimidazolinone tridentate nitrogen ligand was obtained through a one-step condensation.

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