Chiral tripyridine-bis-sulfonylated imidazoline ligand, preparation method thereof and application of chiral tripyridine-bis-sulfonylated imidazoline ligand in asymmetric catalytic reaction

Abstract

The invention discloses a chiral tripyridine-bis (sulfonylation) imidazoline ligand Tpy-bisulidine and a preparation method of the chiral tripyridine-bis (sulfonylation) imidazoline ligand Tpy-bisulidine. According to the invention, corresponding sulfonylation (R, R)-diphenylethylenediamine 1 and tripyridine-dicarboxaldehyde 2 are subjected to a condensation reaction, and a final product, namely the chiral tripyridine-bis-sulfonylation imidazoline ligand (Tpy-bis-sulfonylation imidazoline), is generated. The ligand contains a tripyridine group and an imidazoline group (a nitrogen group of tripyridine and a tertiary amine nitrogen atom of imidazoline belong to electron-rich coordination sites, and N-H of imidazoline can participate in hydrogen-bond interaction), and can form five-membered ring coordination with Lewis metal, so that a chiral ligand metal compound is generated, and the chiral ligand metal compound is used for preparing a chiral ligand. The compound can be used as a chiral ligand in an asymmetric catalytic reaction. Therefore, the method has important application value in the field of asymmetric catalytic synthesis, and the synthesis method is very economical, simple and convenient. And the compound also has good air stability and wide applicability, and has good compatibility with various substituent groups.

Description

Technical Field

[0001] The present invention relates to the technical fields of chiral chemistry and asymmetric catalytic synthesis, and in particular to a chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine), a preparation method thereof, and an application thereof in catalyzing an asymmetric Hetero-Diels-Alder reaction involving α,β-unsaturated enone esters. Background Art

[0002] Chiral pharmaceuticals are a cutting-edge area in the pharmaceutical industry.

[0003] Asymmetric catalysis technology is the most efficient way to obtain chiral molecules. One of the core scientific issues is the creation of superior chiral ligands and catalysts. The design and synthesis of original superior chiral ligands play a key role in the development of asymmetric catalytic reactions and are the most attractive and challenging goals in asymmetric catalysis, which can provide the core technology for the efficient and green synthesis of chiral drugs and drug candidates. In addition, economically viable synthetic routes are also crucial for superior chiral ligands so that they can be widely used. In particular, the nitrogen atom of pyridine belongs to an electron-rich coordination site, and the unique properties of the electron pairs of terpyridine provide opportunities to form complexes with various metals. Some studies have focused on the development of new chiral terpyridine ligands for metal-catalyzed reactions.

[0004] In this context, therefore, we designed and developed a new type of chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine) and tested their application in catalyzing an asymmetric Hetero-Diels-Alder reaction involving α,β-unsaturated enone esters. Based on the design and synthesis of a metal complex of the new type of chiral terpyridine-bisulfonylated imidazoline ligand, our design idea refers to the bionic model diagram of the "crab" shape: the bisulfonylated imidazoline group is analogous to the pincers of two "crabs", and the terpyridine group is analogous to the main body of the "crab" (as Figure 1 shown). Summary of the Invention

[0005] The object of the present invention is to provide a chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine), its preparation method and application. It is an important class of chiral terpyridine ligands. This class of ligands contains a terpyridine group and an imidazoline group (the nitrogen group of terpyridine and the tertiary amine nitrogen atom of imidazoline belong to electron-rich coordination sites, and the N-H of imidazoline can participate in hydrogen bonding), and can form a five-membered ring coordination with a Lewis metal, thereby generating a chiral ligand-metal complex and being used as a chiral ligand in asymmetric catalytic reactions. Therefore, it has important application value in the field of asymmetric catalytic synthesis, and its synthesis method is very economical and simple. It also has good air stability, wide applicability, and good compatibility with various substituents.

[0006] The present invention is realized as follows: A chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine), this compound has the structure shown in general formula (Ⅰ);

[0007]

[0008] In the formula, Ar is a benzene ring or a p-methoxyphenyl ring; R is a benzene ring substituted with hydrogen / methyl / fluorine / trifluoromethyl / isopropyl or trifluoromethyl.

[0009] A preparation method of the chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine), subjecting the corresponding sulfonylated (R,R)-diphenylethylenediamine 1 to a condensation reaction with terpyridine-dialdehyde 2 to generate the target product chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine).

[0010] An example of the synthetic route is as follows:

[0011]

[0012] The present invention also discovers the application of the chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine) in the asymmetric Hetero-Diels-Alder reaction involving α,β-unsaturated enone esters.

[0013] Our design idea is:

[0014]

[0015] The mechanism of the asymmetric Hetero-Diels-Alder reaction catalyzed by the chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine) involving α,β-unsaturated enone esters is exemplified as follows:

[0016]

[0017] By adopting the above technical solution, the corresponding sulfonylated (R,R)-diphenylethylenediamine 1 undergoes a condensation reaction with tripyridine-dialdehyde 2 to generate the final product, chiral tripyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine). This type of ligand contains a tripyridine group and an imidazoline group (the nitrogen groups of tripyridine and the tertiary amine nitrogen atom of imidazoline belong to electron-rich coordination sites, and the N-H of imidazoline can participate in hydrogen bonding), and can form a five-membered ring coordination with a Lewis metal, thereby generating a chiral ligand-metal complex, which is used as a chiral ligand in asymmetric catalytic reactions. Therefore, it has important application value in the field of asymmetric catalytic synthesis, and its synthesis method is very economical and simple. It also has good air stability, wide applicability, and good compatibility with various substituents. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The bionic model diagram of the "crab" shape referred to in the present invention: the bisulfonylated imidazoline group is analogous to the pincers of two "crabs", and the tripyridine group is analogous to the main body of the "crab";

[0019] Figure 2 The design idea and creativity diagram of the chiral tripyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine) synthesized in the present invention;

[0020] Figure 3 The single crystal diagram of the chiral ligand Tpy-bisulidine-9 synthesized in the present invention;

[0021] Figure 4 and Figure 5 The spectral data of the chiral ligand Tpy-bisulidine-1 in the embodiment of the present invention;

[0022] Figure 6 The chiral liquid phase spectral data of the compound 5a in the embodiment of the present invention; DETAILED DESCRIPTION OF THE INVENTION

[0023] (I) Preparation of chiral tripyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine)

[0024]

[0025] Preparation of chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine-1): The raw material sulfonylated (R,R)-diphenylethylenediamine 1a (2.5 eq) and terpyridine-dicarbaldehyde 2 (1 eq, 0.50 mmol) were dissolved in an appropriate amount of dichloromethane and reacted at 30 °C for about 12 h. The reaction solution was post-treated and then purified by column chromatography to obtain a pale yellow solid Tpy-bisulidine-1, melting point: 127.9 - 128.3 °C; yield 56%, >20:1 dr; the results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 H NMR(CDCl3,400MHz)δ:2.27(s,6H),3.89(br s,2H),4.41(d,J=5.6Hz,2H),4.78(d,J=5.6Hz,2H),5.92(s,2H),7.04(d,J=7.6Hz,8H),7.13 - 7.16(m,12H),7.27 - 7.29(m,4H),7.46(d,J=8.0Hz,4H),7.69 - 7.73(m,1H),7.88 - 7.97(m,4H),8.20(d,J=8.0Hz,2H),8.61(d,J=7.6Hz,2H); 13 C NMR(CDCl3,100MHz)δ:20.5,68.9,70.5,77.4,119.9,120.2,123.3,125.8,126.3,126.5,126.6,126.7,127.3,127.5,128.4,133.6,136.5,137.0,138.3,139.1,142.6,154.0,154.5,156.5; HRMS(ESI-TOF)m / z:Calcd.For C 59 H 52 N7O4S2[M+H] + :986.3514; Found:986.3500。

[0026] The preparation methods of chiral ligands Tpy-bisulidine-2 to Tpy-bisulidine-9 prepared by the examples are the same as that of chiral ligand Tpy-bisulidine-1, and the feeding ratios are the same as those of ligand Tpy-bisulidine-1. Ligands Tpy-bisulidine-2 to Tpy-bisulidine-9 can be obtained, and the reaction yields are shown in Table 1. However, it should be emphasized that the examples are intended to illustrate rather than limit the scope of the present invention. The compounds of the present invention are not limited to the content shown in Table 1.

[0027] Table 1 shows the chemical structure of the chiral tripyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine).

[0028]

[0029] Tpy-bisulidine-2: Pale yellow solid, melting point: 136.1 - 136.9 °C, yield 57%, >20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 H NMR(CDCl3, 400 MHz) δ: 3.93(br s, 2H), 4.41(d, J = 6.0 Hz, 2H), 4.79(d, J = 5.6 Hz, 2H), 5.97(s, 2H), 7.03 - 7.06(m, 4H), 7.11 - 7.16(m, 12H), 7.23 - 7.27(m, 8H), 7.37 - 7.41(m, 2H), 7.56(d, J = 4.2 Hz, 4H), 7.69 - 7.73(m, 1H), 7.88(d, J = 7.6 Hz, 2H), 7.94 - 7.98(m, 2H), 8.20(d, J = 7.6 Hz, 2H), 8.62(d, J = 7.6 Hz, 2H); 13 C NMR(CDCl3, 100 MHz) δ: 20.5, 68.9, 70.5, 77.4, 119.9, 120.2, 123.3, 125.8, 126.3, 126.5, 126.6, 126.7, 127.3, 127.5, 128.4, 133.6, 136.5, 137.0, 138.3, 139.1, 142.6, 154.0, 154.5, 156.5; HRMS(ESI-TOF) m / z: Calcd. For C 57 H 48 N7O4S2 [M + H] + : 958.3204; Found: 958.3214.

[0030] Tpy-bisulidine-3: Pale yellow solid, melting point: 134.6 - 135.2 °C, yield 52%, >20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 11H NMR(CDCl3, 400 MHz) δ: 1.99 (s, 6H), 2.25 (s, 12H), 3.73 (br s, 2H), 4.67 (d, J = 6.8 Hz, 2H), 4.86 (d, J = 6.8 Hz, 2H), 6.29 (s, 2H), 6.47 (s, 4H), 6.86 - 7.00 (m, 10H), 7.22 - 7.33 (m, 10H), 7.58 (d, J = 7.6 Hz, 2H), 7.81 - 7.88 (m, 3H), 8.39 (d, J = 7.6 Hz, 2H), 8.62 (d, J = 8.0 Hz, 2H); 13 13C NMR(CDCl3, 100 MHz) δ: 19.7, 21.7, 69.9, 70.6, 76.5, 119.6, 120.2, 122.9, 126.0, 126.1, 126.7, 127.0, 127.7, 130.3, 130.5, 136.7, 136.8, 137.8, 137.9, 139.4, 141.8, 154.1, 154.8, 157.5; HRMS(ESI-TOF) m / z: Calcd. For C 63 H 60 N7O4S2 [M + H] + : 1042.4143; Found: 1042.4147.

[0031] Tpy-bisulidine-4: Pale yellow solid, melting point: 129.1 - 129.7 °C, yield 51%, >20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 1H NMR(CDCl3, 400 MHz) δ: 0.86 - 0.90 (m, 24H), 1.04 (d, J = 7.2 Hz, 12H), 2.63 - 2.70 (m, 2H), 3.77 - 3.84 (m, 4H), 4.99 (s, 4H), 6.25 (s, 2H), 6.81 (s, 4H), 6.90 - 6.96 (m, 6H), 7.07 (d, J = 6.4 Hz, 4H), 7.24 - 7.31 (m, 8H), 7.38 (d, J = 7.2 Hz, 4H), 7.75 - 7.79 (m, 3H), 8.32 (d, J = 8.0 Hz, 2H), 8.61 (d, J = 7.6 Hz, 2H); 1313C NMR(CDCl3, 100 MHz) δ: 22.5, 23.8, 23.9, 25.9, 28.3, 33.1, 69.4, 71.0, 77.2, 119.6, 120.2, 122.4, 122.6, 126.2, 126.3, 126.5, 126.8, 127.0, 127.7, 130.2, 136.5, 136.6, 137.9, 138.5, 150.4, 152.4, 154.0, 155.1, 157.5; HRMS(ESI-TOF) m / z: Calcd. For C 75 H 84 N7O4S2 [M + H] + : 1210.6021; Found: 1210.6023。

[0032] Tpy-bisulidine-5: Pale yellow solid, melting point: 140.5 - 141.2 °C, yield 51%, >20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 1H NMR(CDCl3, 400 MHz) δ: 3.99(br s, 2H), 4.57(d, J = 4.4 Hz, 2H), 4.97(d, J = 4.4 Hz, 2H), 5.97(s, 2H), 7.12 - 7.17(m, 16H), 7.33 - 7.39(m, 8H), 7.46(d, J = 8.0 Hz, 4H), 7.69 - 7.73(m, 1H), 7.78(d, J = 7.2 Hz, 2H), 7.94 - 7.98(m, 2H), 8.13(d, J = 8.0 Hz, 2H), 8.64(d, J = 7.6 Hz, 2H); 13 13C NMR(CDCl3, 100 MHz) δ: 68.9, 70.1, 77.9, 120.2, 120.4, 123.7(q, J = 271.3 Hz), 124.6(q, J = 4.7 Hz), 125.5, 126.4, 126.8, 126.9, 127.0, 127.4, 127.7, 133.0(q, J = 34.0 Hz), 136.5, 136.9, 137.0, 138.1, 138.8, 140.8, 153.9, 154.8, 155.5; HRMS(ESI-TOF) m / z: Calcd. For C 59 H 46 F6N7O4S2 [M + H] + : 1094.2955; Found: 1094.2970。

[0033] Tpy-bisulidine-6: Pale yellow solid, melting point: 132.1 - 132.9 °C, yield 52%, 18:1 dr; Results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 H NMR(CDCl3, 400 MHz) δ: 4.01(br s, 2H), 4.73(d, J = 4.4 Hz, 2H), 5.20(d, J = 4.4 Hz, 2H), 6.06(s, 2H), 7.11 - 7.17(m, 6H), 7.22 - 7.25(m, 2H), 7.28 - 7.32(m, 4H), 7.35(d, J = 7.2 Hz, 4H), 7.46 - 7.47(m, 8H), 7.53(s, 2H), 7.70 - 7.73(m, 3H), 7.94 - 7.98(m, 2H), 8.09(d, J = 7.6 Hz, 2H), 8.62(d, J = 8.0 Hz, 2H); 13 C NMR(CDCl3, 100 MHz) δ: 69.3, 69.5, 77.9, 119.9, 120.9, 122.5, 124.0(q, J = 271.3 Hz), 124.5(q, J = 4.7 Hz), 125.5, 126.2, 126.5, 127.1, 127.2, 127.6, 127.9, 131.0(q, J = 34.0 Hz), 136.4, 137.1, 137.9, 138.2, 141.5, 153.7, 154.5, 155.2; HRMS(ESI-TOF) m / z: Calcd.ForC 61 H 44 F 12 N7O4S2[M + H] + : 1230.2765; Found: 1230.2779。

[0034] Tpy-bisulidine-7: Pale yellow solid, melting point: 138.0 - 138.8 °C, yield 47%, 16:1 dr; Results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 H NMR(CDCl3, 400 MHz) δ: 4.33(br s, 2H), 4.82(s, 2H), 5.17(s, 2H), 5.95(s, 2H), 7.17 - 7.19(m, 4H), 7.24 - 7.27(m, 8H), 7.39(d, J = 7.2 Hz, 4H), 7.59 - 7.61(m, 4H), 7.67 - 7.71(m, 1H), 7.74(d, J = 7.6 Hz, 2H), 7.94 - 7.98(m, 2H), 8.12(d, J = 8.0 Hz, 2H), 8.67(d, J = 7.6 Hz, 2H);13 13C NMR (CDCl3, 100 MHz) δ: 67.9, 69.1, 77.5, 119.8, 120.3, 124.1, 124.5, 125.5, 126.1 (d, J CF = 31.2 Hz), 127.1, 135.9, 136.6, 137.9, 138.3, 142.9 (d, J CF = 272.1 Hz), 153.1, 153.2, 154.0; HRMS (ESI-TOF) m / z: Calcd. For C 57 H 38 F 10 N7O4S2 [M+H] + : 1138.2262; Found: 1138.2257.

[0035] Tpy-bisulidine-8: Pale yellow solid, melting point: 137.8 - 138.2 °C, yield 51%, 16:1 dr; Results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 1H NMR (CDCl3, 400 MHz) δ: 4.39 (br s, 2H), 4.74 (s, 2H), 5.38 (s, 2H), 6.05 (s, 2H), 7.23 - 7.25 (m, 6H), 7.31 (d, J = 7.2 Hz, 2H), 7.36 - 7.40 (m, 4H), 7.48 - 7.52 (m, 7H), 7.61 - 7.64 (m, 2H), 7.90 - 7.95 (m, 4H), 8.44 (d, J = 8.0 Hz, 2H), 8.70 (d, J = 7.6 Hz, 2H); 13 13C NMR (CDCl3, 100 MHz) δ: 69.4, 69.8, 79.2, 120.5, 120.6, 121.0, 124.3, 125.6, 125.9, 127.1, 127.3, 127.7, 128.0, 136.9, 137.2, 137.4, 138.6, 153.5 (q, J = 272.1 Hz), 153.8, 154.8; HRMS (ESI-TOF) m / z: Calcd. For C 47 H 38 F6N7O4S2 [M+H] + : 942.2329; Found: 942.2337.

[0036] Tpy-bisulidine-9: Pale yellow solid, melting point: 132.3 - 132.8 °C, yield 53%, >20:1 dr; Results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 11H NMR(CDCl3, 400 MHz) δ: 2.30 (s, 6H), 3.66 (s, 6H), 3.70 (s, 6H), 3.79 (br s, 2H), 4.31 (d, J = 6.4 Hz, 2H), 4.61 (d, J = 6.4 Hz, 2H), 5.91 (s, 2H), 6.64 - 6.68 (m, 8H), 6.92 (d, J = 8.4 Hz, 4H), 7.08 - 7.17 (m, 8H), 7.50 (d, J = 8.4 Hz, 4H), 7.69 - 7.73 (m, 1H), 7.88 - 7.97 (m, 4H), 8.20 (d, J = 7.6 Hz, 2H), 8.60 (d, J = 7.2 Hz, 2H); 13 13C NMR(CDCl3, 100 MHz) δ: 20.5, 54.2, 54.3, 68.4, 70.3, 77.0, 112.6, 112.8, 120.0, 120.1, 123.1, 126.8, 127.0, 127.5, 128.4, 130.0, 130.8, 133.7, 136.5, 136.9, 142.6, 154.0, 154.5, 157.0, 157.9, 158.1; HRMS(ESI-TOF) m / z: Calcd. For C 63 H 59 N7NaO8S2 [M + H] + : 1128.3756; Found: 1128.3740.

[0037] (2) Application of chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine) as a ligand in the asymmetric Hetero-Diels-Alder reaction of α,β-unsaturated enone esters

[0038] The chiral terpyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine) of formula (1) in the present invention. This type of ligand contains a terpyridine group and an imidazoline group (the nitrogen groups of terpyridine and the tertiary amine nitrogen atom of imidazoline belong to electron-rich coordination sites, and the N-H of imidazoline can participate in hydrogen bonding), and can form a five-membered ring coordination with a Lewis metal, thereby generating a chiral ligand-metal complex for use in the asymmetric Hetero-Diels-Alder reaction of α,β-unsaturated enone esters. It should be emphasized that the chiral ligand Tpy-bisulidine in the present invention is not limited to being used as a chiral ligand only in the asymmetric Hetero-Diels-Alder reaction of α,β-unsaturated enone esters.

[0039] Example 1: Application of Chiral Ligand Tpy-bisulidine with Various Substituents in Asymmetric Catalytic Reactions

[0040] To demonstrate the application value of the developed chiral ligand Tpy-bisulidine in an asymmetric catalytic system, we selected the asymmetric Hetero-Diels-Alder reaction of α,β-unsaturated enone ester 3a and dihydrofuran 4 as the template reaction, and selected various substituted compounds Tpy-bisulidine-1 to Tpy-bisulidine-9 as chiral ligands to in-situ generate chiral complexes with Lewis acid Ni(OTf)2 to verify the asymmetric catalytic effect of chiral ligand Tpy-bisulidine (Table 2).

[0041] Table 2 shows the application of chiral ligand Tpy-bisulidine with various substituents in asymmetric catalytic reactions

[0042]

[0043] Experimental conclusion: The asymmetric Hetero-Diels-Alder template reaction of α,β-unsaturated enone ester 3a and dihydrofuran 4 was selected as the evaluation index. The experimental results showed that such chiral ligands Tpy-bisulidine-1 to Tpy-bisulidine-9 with various substituents as shown in formula (1) all showed asymmetric catalytic effects in the asymmetric Hetero-Diels-Alder reaction of α,β-unsaturated enone ester 3a and dihydrofuran 4, and could be developed into a new dominant chiral tripyridine-bisulfonylated imidazoline ligand (Tpy-bisulidine), which was worthy of further in-depth study.

[0044] Example 2: Application of Chiral Ligand Tpy-bisulidine-6 in Asymmetric Catalytic Reactions

[0045] To demonstrate the application value of the developed chiral ligand Tpy-bisulidine-6 in an asymmetric catalytic system, we selected the asymmetric Hetero-Diels-Alder reaction of α,β-unsaturated enone esters 3 with various substituents and dihydrofuran 4 as the template reaction to verify the catalytic effect of chiral ligand Tpy-bisulidine-6 (Table 3).

[0046] Table 3 shows the application of chiral ligand Tpy-bisulidine-6 in asymmetric catalytic reactions

[0047]

[0048] Experimental conclusion: The asymmetric catalytic Hetero-Diels-Alder template reaction involving α,β-unsaturated enone esters 3 and dihydrofuran 4 was selected as the evaluation index. The experimental results showed that the chiral complex in situ formed by the chiral ligand Tpy-bisulidine-6 of formula (1) and Ni(OTf)2 exhibited asymmetric catalytic effects in the asymmetric catalytic Hetero-Diels-Alder reactions of α,β-unsaturated enone esters 3 with various substituents and dihydrofuran 4, and it was capable of developing into a new dominant chiral ligand Tpy-bisulidine, which was worthy of further in-depth study.

Claims

1. A chiral terpyridine-bis-sulfonylated imidazoline ligand Tpy-bisulidine, characterized in that: The compound has a structure shown in general formula (Ⅰ); In the formula, Ar is a benzene ring or a p-methoxybenzene ring; R is a benzene ring substituted by hydrogen / methyl / fluorine / trifluoromethyl / isopropyl or trifluoromethyl. Among them, the chiral tripyridine-bisulfonylated imidazoline ligand Tpy-bisulidine is specifically one of the following structural formulas:

2. A method for preparing the chiral terpyridine-bisulfonylated imidazoline ligand Tpy-bisulidine as described in claim 1, characterized in that: The corresponding sulfonylated (R,R)-diphenylethylenediamine 1 reacts with tripyridine-dialdehyde 2 by condensation reaction to generate the target product chiral tripyridine-bisulfonylated imidazoline ligand Tpy-bisulidine; The synthetic route is as follows:

3. Application of the chiral tripyridine-bisulfonylated imidazoline ligand Tpy-bisulidine as claimed in claim 1 in the asymmetric Hetero-Diels-Alder reaction catalyzed by the ligand and involving α,β-unsaturated enone ester.

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