Chiral dinitrogen-oxygen ligands based on bipyridine bridging, preparation method thereof and application of chiral dinitrogen-oxygen ligands in asymmetric catalytic reaction

Abstract

The invention discloses a chiral dinitrogen-oxygen ligand based on bipyridine bridging, a preparation method of the chiral dinitrogen-oxygen ligand and application of the chiral dinitrogen-oxygen ligand in asymmetric catalytic reaction, and belongs to the field of organic synthesis and asymmetric catalysis. The invention provides a chiral dinitrogen-oxygen ligand based on bipyridine bridging, which is characterized in that two chiral nitrogen-oxygen units (spiro or long-arm structures) with clear structures are bridged through a rigid bipyridine skeleton, so that a chiral catalytic microenvironment with high rigidity and clear spatial orientation is accurately constructed. According to the structural design, nitrogen atoms of dipyridyl and oxygen atoms of nitrogen-oxygen groups are effectively integrated to serve as multiple coordination sites, efficient coordination with multiple metal ions such as Mn (II), Fe (II), Co (II), Ni (II), Cu (II) and Zn (II) can be achieved, a stable six-membered ring chelating structure is preferentially generated, and therefore the high-performance chiral ligand-metal composite material is prepared. The catalyst shows an excellent catalytic effect in an asymmetric cycloaddition reaction.

Description

Technical Field

[0001] This invention relates to the fields of organic synthesis and asymmetric catalysis, and in particular to a class of bipyridine-bridged chiral dinitrogen oxide ligands, their preparation methods, and their applications in asymmetric catalytic reactions. Background Technology

[0002] Chiral nitrogen-oxygen ligands, such as bipyridine oxazoline (PyBox) and bisoxazoline (Box), have become key tools in the field of modern asymmetric catalysis. These ligands can coordinate with metal centers to construct Lewis acid catalysts with well-defined chiral environments, and have been successfully applied to various enantioselective transformation processes such as cyclopropanation, aldol condensation, and the Mannich reaction.

[0003] Despite significant achievements in this field, current research focuses on developing novel nitrogen-oxygen ligands with higher structural rigidity, superior chiral transfer efficiency, and broader substrate versatility. Among these, connecting two highly structured chiral nitrogen-oxygen units via a rigid bipyridine bridge, and precisely controlling the relative spatial orientation and electronic properties of the two metal coordination sites, may yield unique catalytic performance. However, further adding rigid structures such as spirocyclic or fused-ring frameworks to the rigid bipyridine framework to construct chiral bis-nitrogen-oxygen ligands with even higher rigidity has not yet been reported in the literature. Summary of the Invention

[0004] The purpose of this invention is to provide a class of bipyridine-bridged chiral dinitrogenoxa ligands, their preparation methods, and their applications in asymmetric catalytic reactions, in order to solve the aforementioned problems in the prior art.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] One of the technical solutions of this invention is to provide a class of chiral bis(oxy) ligands based on bipyridine bridging, wherein the chiral bis(oxy) ligands based on bipyridine bridging are spirocyclic chiral oxy-oxygen oxide-bipyridine ligands or long-arm chiral oxy-oxygen oxide-bipyridine ligands;

[0007] The spirocyclic chiral oxynitride-bipyridine ligand has the structure shown in Formula I:

[0008] ;

[0009] In Formula I, Ar is a phenyl, an alkyl-substituted phenyl, a cycloalkyl-substituted phenyl, or a halophenyl;

[0010] The long-arm chiral oxynitride-bipyridine ligand has a structure as shown in Formula II:

[0011] ;

[0012] In Formula II, R1 and R2 are independently hydrogen-based, alkyl-based, halogen-substituent, or haloalkyl-based, and m is 1 or 2.

[0013] Preferably, in Formula I, the alkyl-substituted phenyl group has 1 to 5 carbon atoms; the cycloalkyl-substituted phenyl group has 3 to 6 carbon atoms; and the halophenyl group is a fluorophenyl or a chlorophenyl.

[0014] In Formula II, the alkyl group has 1 to 5 carbon atoms; the halogen substituent is fluorine or chlorine; and the haloalkyl group is trifluoromethyl.

[0015] Preferably, the spirocyclic chiral oxynitride-bipyridine ligand has a structure shown in any one of formulas L1 to L6:

[0016] .

[0017] Preferably, the long-arm chiral oxynitride-bipyridine ligand has a structure shown in any one of formulas L7 to L18:

[0018] ;

[0019] The second technical solution of the present invention provides a method for preparing the above-mentioned chiral dioxo-oxygen ligand based on bipyridine bridging, comprising the following steps:

[0020] Using compound C or compound D as a precursor and m-chloroperoxybenzoic acid as an oxidant, a nitrogen oxidation reaction is carried out in a solvent to obtain the chiral bis(nitrogen oxide) ligand based on bipyridine bridging.

[0021] When compound C is used as a raw material, the product has the structure shown in Formula I;

[0022] When compound D is used as a raw material, the product has the structure shown in Formula II;

[0023] The structure of compound C is shown in formula C, and the structure of compound D is shown in formula D:

[0024] , .

[0025] Preferably, the molar ratio of the precursor to m-chloroperoxybenzoic acid is 1:2~3; the solvent is chloroform; the concentration of the precursor in the solvent is 0.1M~0.2M; and the time of the nitrogen oxidation reaction is 20min~60min.

[0026] Preferably, the preparation method of compound C includes the following steps:

[0027] Spirocyclic piperidine amide with the structure shown in compound A and 2,2'-bipyridine-6,6'-dicarboxaldehyde were mixed in an alcohol solvent and subjected to a bridging reaction to obtain compound C.

[0028] The molar ratio of compound A to bipyridine-6,6'-dicarboxaldehyde is 2-3:1; the alcohol solvent is ethanol; the concentration of compound A in the alcohol solvent is 0.1M-0.2M; the bridging reaction is carried out at 80℃-85℃ for 6h-24h; compound A is shown below:

[0029] .

[0030] Preferably, the preparation method of compound D includes the following steps:

[0031] Chiral fused-ring proline with the structure shown in compound B and 2,2'-bipyridine-6,6'-dicarboxaldehyde were mixed in an alcohol solvent and a bridging reaction was carried out to obtain compound D.

[0032] The molar ratio of compound B to bipyridine-6,6'-dicarboxaldehyde is 2~3:1; the alcohol solvent is ethanol; the concentration of compound B in the alcohol solvent is 0.1M~0.2M; the bridging reaction is carried out at 80℃~85℃ for 6h~24h; compound B is shown below:

[0033] .

[0034] The third technical solution of the present invention provides an application of the above-mentioned bipyridine-bridged chiral dinitrogenoxa ligand in asymmetric catalytic reactions.

[0035] Fourth technical solution of the present invention: A method for an asymmetric cycloaddition reaction involving α,β-unsaturated acyl imidazole compounds, comprising the following steps:

[0036] The 3-vinyl-1H-indole compound, α,β-unsaturated acylimidazolium compound, metal Lewis acid, the above-mentioned bipyridine-bridged chiral dioxo-oxygen ligand, and solvent were mixed and subjected to an asymmetric cycloaddition reaction to complete the preparation.

[0037] The present invention utilizes a bipyridine-bridged chiral dioxygen ligand with a robust diacidoxy group that chelates the metal center; the bipyridine unit precisely controls the chiral microenvironment from both sides. Furthermore, the diacidoxy group also possesses the ability to form hydrogen bonds, enabling effective interaction with reactants.

[0038] The beneficial technical effects of the present invention are as follows:

[0039] This invention provides a novel class of bipyridine-bridged chiral bis(nitrogen-oxygen) ligands that bridge two well-defined chiral nitrogen-oxygen units (spirocyclic or long-arm structures) through a rigid bipyridine framework, thereby precisely constructing a highly rigid chiral catalytic microenvironment with a well-defined spatial orientation. This structural design effectively integrates the nitrogen atom of the bipyridine and the oxygen atom of the nitrogen group as multiple coordination sites, enabling efficient coordination with various metal ions such as Mn(II), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II), preferentially forming stable six-membered ring chelate structures, thus yielding high-performance chiral ligand-metal composite materials. The ligand-metal composite materials designed in this invention exhibit excellent catalytic performance in asymmetric cycloaddition reactions. Using the asymmetric cycloaddition reaction involving α,β-unsaturated acylimidazoles as a model, this invention has verified its high enantioselectivity and broad substrate applicability.

[0040] These ligands exhibit good stability in air, are suitable for various organic solvent reaction systems, and demonstrate good compatibility with various functional group substituents. From a synthetic perspective, the preparation method of the target ligand is simple and efficient, requiring only amine-aldehyde condensation and nitric oxidation reactions. The starting materials are inexpensive and readily available, resulting in low preparation costs. The obtained products have highly modifiable and controllable structures, are insensitive to water and air, are easy to store and handle, and have good application value. Attached Figure Description

[0041] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0042] Figure 1 The 1H NMR spectrum of the spirocyclic chiral nitride-bipyridine ligand L1;

[0043] Figure 2 The carbon NMR spectrum of spirocyclic chiral nitride-bipyridine ligand L1;

[0044] Figure 3 The 1H NMR spectrum of the long-arm chiral nitride-bipyridine ligand L7;

[0045] Figure 4 The carbon NMR spectrum of the long-arm chiral nitride-bipyridine ligand L7;

[0046] Figure 5 The 1H NMR spectrum of the long-arm chiral nitride-bipyridine ligand L13;

[0047] Figure 6 The carbon NMR spectrum of the long-arm chiral nitride-bipyridine ligand L13;

[0048] Figure 7 The above is a synthetic route diagram of the asymmetric catalytic reaction of Example 6 of the present invention and the structural formulas of ligands L1 to L19. Detailed Implementation

[0049] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0050] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0051] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. It should be noted that any aspects of this invention not described in detail are conventional practices in the art and are not the focus of this invention.

[0052] The terms “comprising,” “including,” “having,” “containing,” etc., used in this invention are all open-ended terms, meaning that they include but are not limited to.

[0053] This invention discloses a class of chiral bis(oxy) ligands based on bipyridine bridging, wherein the chiral bis(oxy) ligands based on bipyridine bridging are spirocyclic chiral oxy-oxygen oxide-bipyridine ligands or long-arm chiral oxy-oxygen oxide-bipyridine ligands;

[0054] The spirocyclic chiral oxynitride-bipyridine ligand has the structure shown in Formula I:

[0055] ;

[0056] In Formula I, Ar is a phenyl, an alkyl-substituted phenyl, a cycloalkyl-substituted phenyl, or a halophenyl;

[0057] The long-arm chiral oxynitride-bipyridine ligand has a structure as shown in Formula II:

[0058] ;

[0059] In Formula II, R1 and R2 are independently hydrogen-based, alkyl-based, halogen-substituent, or haloalkyl-based, and m is 1 or 2.

[0060] Furthermore, in Formula I, the alkyl-substituted phenyl group has 1 to 5 carbon atoms in the alkyl group; the cycloalkyl-substituted phenyl group has 3 to 6 carbon atoms in the cycloalkyl group; and the halophenyl group is a fluorophenyl or a chlorophenyl.

[0061] In Formula II, the alkyl group has 1 to 5 carbon atoms; the halogen substituent is fluorine or chlorine; and the haloalkyl group is trifluoromethyl.

[0062] This invention also discloses a method for preparing the above-mentioned chiral dioxo-oxo ligand based on bipyridine bridging, comprising the following steps:

[0063] Using compound C or compound D as a precursor and m-chloroperoxybenzoic acid as an oxidant, a nitrogen oxidation reaction is carried out in a solvent to obtain the chiral bis(nitrogen oxide) ligand based on bipyridine bridging.

[0064] When compound C is used as a raw material, the product has the structure shown in Formula I;

[0065] When compound D is used as a raw material, the product has the structure shown in Formula II;

[0066] The structure of compound C is shown in formula C; the structure of compound D is shown in formula D;

[0067] , .

[0068] Furthermore, the molar ratio of the precursor to m-chloroperoxybenzoic acid is 1:2~3; the solvent is chloroform; the concentration of the precursor in the solvent is 0.1M~0.2M; the time of the nitrogen oxidation reaction is 20min~60min, preferably 20min, and the temperature is room temperature.

[0069] Furthermore, the preparation method of compound C includes the following steps:

[0070] Spirocyclic piperidine amide with the structure shown in compound A and 2,2'-bipyridine-6,6'-dicarboxaldehyde were mixed in an alcohol solvent and subjected to a bridging reaction to obtain compound C.

[0071] The molar ratio of compound A to bipyridine-6,6'-dicarboxaldehyde is 2~3:1, preferably 2.5:1; the alcohol solvent is methanol or ethanol, preferably ethanol; the concentration of compound A in the alcohol solvent is 0.1M~0.2M; the bridging reaction temperature is 80℃~85℃, and the time is 6h~24h; compound A is shown below;

[0072] .

[0073] Furthermore, the preparation method of compound D includes the following steps:

[0074] Chiral fused-ring proline with the structure shown in compound B and 2,2'-bipyridine-6,6'-dicarboxaldehyde were mixed in an alcohol solvent and a bridging reaction was carried out to obtain compound D.

[0075] The molar ratio of compound B to bipyridine-6,6'-dicarboxaldehyde is 2~3:1, preferably 2.5:1; the alcohol solvent is methanol or ethanol, preferably ethanol; the concentration of compound B in the alcohol solvent is 0.1M~0.2M; the bridging reaction temperature is 80℃~85℃, preferably 80℃, and the time is 6h~24h, preferably 20h; compound B is shown below;

[0076] .

[0077] Furthermore, after the nitrogen oxidation reaction, a purification step is also included; the purification method is a purification method combining silica gel column chromatography and recrystallization of an ether / n-hexane system; the eluent for the silica gel column chromatography is methanol and dichloromethane, and the volume ratio of methanol to dichloromethane is 1:1-10.

[0078] The present invention also discloses the application of the above-mentioned bipyridine-bridged chiral dinitrogen oxide ligand in asymmetric catalytic reactions.

[0079] This invention also discloses a method for an asymmetric cycloaddition reaction involving α,β-unsaturated acyl imidazole compounds, comprising the following steps:

[0080] A mixture of 3-vinyl-1H-indole compounds, α,β-unsaturated acylimidazolium compounds, a metal Lewis acid, the aforementioned bipyridine-bridged chiral dinitroxide ligand, and a solvent is subjected to an asymmetric cycloaddition reaction to form a chiral ligand-metal complex.

[0081] Furthermore, the metal ion in the metal Lewis acid is Mn. 2+ Fe 2+ Co 2+ Ni 2+ Cu 2+ and Zn 2+ One or more of the following, preferably Ni(OTf)2; the amount of the chiral dinitrogenoxa ligand based on bipyridine bridging is 5.5% to 12% of the molar amount of the α,β-unsaturated acyl imidazole compound; the solvent is dichloromethane; the asymmetric addition cyclization reaction does not require inert gas protection.

[0082] Furthermore, the 3-vinyl-1H-indole compound is 3-vinyl-1H-indole ( ).

[0083] Furthermore, the α,β-unsaturated acylimidazolium compounds are shown in Formula E:

[0084]

[0085] In Formula E, R3 is an alkyl group, preferably having 1 to 10 carbon atoms, more preferably 1 to 6, and even more preferably methyl; R2 is a phenyl group, a substituted phenyl group, or a heterocyclic group; the substituent in the substituted phenyl group is preferably an alkyl group or an alkoxy group; the alkyl group preferably has 1 to 10 carbon atoms, more preferably 1 to 5, and even more preferably methyl; the alkoxy group preferably has 1 to 10 carbon atoms, more preferably 1 to 5, and even more preferably methoxy.

[0086] In this invention, the reaction formula for the asymmetric addition cyclization reaction between the 3-vinyl-1H-indole and the α,β-unsaturated acylimidazolium compound is as follows:

[0087]

[0088] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0089] Unless otherwise specified, "room temperature" in this invention refers to 10-30°C.

[0090] All raw materials used in the following embodiments and comparative examples of the present invention are commercially available products.

[0091] Example 1

[0092] The synthetic route for a class of spirocyclic chiral nitride-bipyridine ligands L1 is as follows:

[0093]

[0094] Ar represents phenyl.

[0095] The preparation method of the above-mentioned spirocyclic chiral oxynitride-bipyridine ligand L1 is as follows:

[0096] Compound A (2.5 equiv, 2.5 mmol) was added to a round-bottom flask equipped with a magnetic stirrer. ), and then compound F (1.0 equiv, 1.0 mmol, 2,2'-bipyridine-6,6'-dicarboxaldehyde), and finally dissolved in an appropriate amount of anhydrous ethanol (EtOH), followed by reflux in an oil bath for 6 h, and then rapid column chromatography (eluents were methanol and dichloromethane, with a volume ratio of methanol to dichloromethane of 1:20) to give intermediate C ( Intermediate C and m-chloroperoxybenzoic acid (2.5 equiv, m-CPBA) were added to a reaction tube and dissolved in chloroform (CHCl3). The reaction system was stirred at room temperature (rt) for 20 min. The solvent was removed by rotary evaporation, and the solution was purified by dry column chromatography (eluents were methanol and dichloromethane, with a volume ratio of methanol to dichloromethane of 1:10) to obtain a white solid spirocyclic chiral nitride-bipyridine ligand L1 (melting point: 196.6-198.2 °C; overall yield 52%, diastereomeric ratio (dr) > 20:1).

[0097] The NMR and high-resolution mass spectrometry results for L1 are as follows: 1 H NMR (400 MHz, CDCl3) δ 8.30(d, J = 7.9 Hz, 2H), 7.79 (t, J = 7.8 Hz, 2H), 7.46 (d, J = 8.0 Hz, 4H), 7.29(dt, J = 10.6, 7.8 Hz, 6H), 7.11 (t, J = 7.4 Hz, 2H), 5.79 (s, 2H), 4.43 (dd,J = 8.9, 3.6 Hz, 2H), 3.30 (d, J = 9.8 Hz, 2H), 3.11 (d, J = 9.8 Hz, 2H), 2.31 (dd, J = 13.0, 3.6 Hz, 2H), 2.20 (dd, J = 13.0, 9.0 Hz, 2H), 0.74 – 0.62(m, 8H). 13 C NMR (101 MHz, CDCl3) δ 175.3, 157.3, 155.8, 138.4, 137.7, 129.1,125.3, 121.8, 121.1, 121.0, 85.5, 65.9, 64.5, 36.6, 21.4, 11.7, 10.2. HRMS(APCI) m / z calcd for C 38 H 37 N6O4 + (M+H) +641.2871, found 641.2868.

[0098] Figure 1 The image shows the 1H NMR spectrum of the spirocyclic chiral nitride-bipyridine ligand L1.

[0099] Figure 2 The image shows the carbon NMR spectrum of the spirocyclic chiral nitride-bipyridine ligand L1.

[0100] Example 2

[0101] The only difference from Example 1 is that the compound A, in which Ar is phenyl, was replaced with equimolar amounts of the corresponding compounds of 3,5-bis(trifluoromethyl)phenyl, 4-chlorophenyl, 4-fluorophenyl, 4-cyclopropylphenyl, or 4-methylphenyl; the resulting products are designated L2, L3, L4, L5, and L6, respectively. The structural identification data for each product are as follows:

[0102] The chiral tetradentate dinitroxide ligand L2 prepared in this embodiment is a white solid with a melting point of 184.5-86.1℃; overall yield 32%; >20:1 dr. The NMR and high-resolution mass spectrometry results are as follows: ¹H NMR (400 MHz, DMSO) δ 8.15 (d, J = 6.3 Hz, 6H), 8.05 (t, J = 7.8 Hz, 2H), 7.82 – 7.67 (m, 4H), 7.13 (d, J = 6.4 Hz, 2H), 4.69 (dd, J = 8.6, 2.6 Hz, 2H), 4.46 (d, J = 11.8 Hz, 2H), 3.74 (dd, J = 11.8, 4.3 Hz, 2H), 2.65 (ddd, J = 8.6, 2.6 Hz, 2H), 2.65 (ddd, J = 11.8, 4.3 Hz, 2H). J = 11.4, 8.6, 2.6Hz, 2H), 2.24 (dd, J = 13.2, 2.2 Hz, 2H), 0.88 – 0.75 (m, 4H), 0.69 – 0.59(m, 4H). 13 C NMR (101 MHz, DMSO) δ 170.6, 154.1, 150.4, 138.1, 137.8, 131.2, 130.8, 128.4, 124.1, 122.6, 121.4, 121.2, 119.2, 115.9, 87.5, 80.3, 78.4,34.02, 19.83, 11.3, 10.8. 19F NMR (376 MHz, DMSO) δ -62.25. HRMS (APCI) m / zcalcd for C 42 H 33 F 12 N6O4 + (M+H) + 913.2366, found 913.2363.

[0103] The bipyridine chiral tetradentate dinitroxide ligand L3 prepared in this embodiment is a white solid with a melting point of 180.8-182.4℃ and an overall yield of 46%; its dr ratio is >20:1. The NMR and high-resolution mass spectrometry results are as follows: 1 H NMR (400 MHz, CD3OD)δ 8.37 (dd, J = 8.0, 0.9 Hz, 2H), 8.02 (t, J = 7.8 Hz, 2H), 7.73 (dd, J =7.6, 0.9 Hz, 2H), 7.43 – 7.38 (m, 4H), 7.26 – 7.20 (m, 4H), 6.80 (s, 2H), 4.81 (dd, J = 8.5, 2.3 Hz, 2H), 4.38 (d, J = 11.9 Hz, 2H), 3.87 (d, J = 11.9Hz, 2H), 2.74 (dd, J = 13.3, 8.5 Hz, 2H), 2.41 (dd, J = 13.3, 2.3 Hz, 2H), 0.99 – 0.86 (m, 5H), 0.83 – 0.73 (m, 4H). 13 C NMR (101 MHz, CD3OD) δ 170.5,156.4, 151.5, 139.6, 135.6, 133.2, 130.3, 129.1, 125.31, 123.5, 90.2, 81.2,79.7, 35.2, 20.9, 12.2, 12.0. HRMS (APCI) m / z calcd for C 38 H 35 Cl2N6O4 + (M+H) + 709.2091, found 709.2086.

[0104] The bipyridine chiral tetradentate dinitroxide ligand L4 prepared in this embodiment is a white solid with a melting point of 208.6-210.2℃; overall yield 37%; >20:1 dr; the NMR and high-resolution mass spectrometry results are as follows: 1 H NMR (400 MHz, DMSO)δ 8.21 (dd, J = 7.9, 1.0 Hz, 2H), 8.02 (t, J = 7.8 Hz, 2H), 7.70 (dd, J =7.7, 1.0 Hz, 2H), 7.55 – 7.44 (m, 4H), 7.26 – 7.12 (m, 4H), 6.83 (s, 2H), 4.53 (dd, J = 8.4, 2.2 Hz, 2H), 4.31 (d, J = 11.7 Hz, 2H), 3.73 (d, J = 11.7Hz, 2H), 2.63 (dd, J = 13.1, 8.4 Hz, 2H), 2.16 (dd, J = 13.2, 2.2 Hz, 2H), 0.85 – 0.74 (m, 4H), 0.70 – 0.60 (m, 4H). 13 C NMR (101 MHz, DMSO) δ 169.6,160.9, 158.5, 154.0, 151.6, 137.9, 132.3, 132.3, 127.9, 124.7, 124.7, 120.9,116.0, 115.8, 88.4, 80.9, 78.9, 33.9, 19.7, 11.7, 10.5. 19 F NMR (376 MHz, DMSO) δ -115.25. HRMS (APCI) m / z calcd for C 38 H 35 F2N6O4 + (M+H) + 677.2682, found 677.2679.

[0105] The bipyridine chiral tetradentate dinitroxide ligand L5 prepared in this embodiment is a white solid with a melting point of 200.4-202.0 °C and an overall yield of 40%; its dr ratio is >20:1. The NMR and high-resolution mass spectrometry results are as follows: 1H NMR (400 MHz, DMSO)δ 8.20 (dd, J = 7.9, 1.0 Hz, 2H), 8.01 (t, J = 7.8 Hz, 2H), 7.69 (dd, J =7.7, 1.0 Hz, 2H), 7.38 – 7.24 (m, 4H), 7.07 – 6.94 (m, 4H), 6.78 (s, 2H), 4.50 (dd, J = 8.3, 2.0 Hz, 2H), 4.27 (d, J = 11.7 Hz, 2H), 3.74 (d, J = 11.7Hz, 2H), 2.63 (dd, J = 13.1, 8.4 Hz, 2H), 2.14 (dd, J = 13.0, 2.1 Hz, 2H), 1.78 (td, J = 8.4, 4.2 Hz, 2H), 0.91 – 0.74 (m, 8H), 0.69 – 0.48 (m, 8H). 13 CNMR (101 MHz, DMSO) δ 169.3, 154.0, 151.8, 141.8, 137.8, 133.3, 127.8, 125.9,122.3, 120.7, 88.4, 81.0, 78.9, 33.9, 19.7, 14.6, 11.9, 10.4, 9.4, 9.3. HRMS(APCI) m / z calcd for C 44 H 45 N6O4 + (M+H) + 721.3497, found 721.3493.

[0106] The bipyridine chiral tetradentate dinitroxide ligand L6 prepared in this embodiment is a white solid with a melting point of 175.6-177.2℃; overall yield 52%; >20:1 dr; the NMR and high-resolution mass spectrometry results are as follows: 1H NMR (400 MHz, CD3OD)δ 8.39 (dt, J = 8.1, 1.6 Hz, 2H), 7.98 (t, J = 7.8 Hz, 2H), 7.68 (dt, J =7.9, 1.6 Hz, 2H), 7.27 – 7.22 (m, 4H), 7.05 – 6.99 (m, 4H), 6.73 (d, J = 2.2Hz, 2H), 4.82 (dd, J = 8.5, 2.4 Hz, 2H), 4.37 (d, J = 11.9 Hz, 2H), 3.85 (d,J = 11.9 Hz, 2H), 2.71 (dd, J = 13.3, 8.5 Hz, 2H), 2.37 (dd, J = 13.3, 2.4Hz, 2H), 2.14 (d, J = 4.9 Hz, 6H), 0.95 – 0.83 (m, 4H), 0.80 – 0.70 (m, 4H).13C NMR (101 MHz, CD3OD) δ 170.4, HRMS (APCI) m / z calcd for C 40 H4N6O4 + (M+H) + 669.3184, found 669.3180.

[0107] Example 3

[0108] The synthetic route for a class of long-arm chiral nitrogen oxide-bipyridine ligands L7 is as follows:

[0109]

[0110] In compound A, the R1 and R2 groups are hydrogen groups, and m=0.

[0111] The preparation method of the above-mentioned long-arm chiral oxynitride-bipyridine ligand L7 is as follows:

[0112] Compound B (2.5 equiv, 2.5 mmol) was added to a round-bottom flask equipped with a magnetic stirrer. ), and then compound F (1.0 equiv, 1.0 mmol, Finally, an appropriate amount of anhydrous ethanol (EtOH) was added to dissolve it, and then the mixture was heated under reflux in an oil bath for 6 h. Rapid column chromatography was then performed (the eluents were methanol and dichloromethane, with a volume ratio of methanol to dichloromethane of 1:20) to obtain intermediate D. Intermediate D and m-chloroperoxybenzoic acid (2.5 equiv, m-CPBA) were added to a reaction tube and dissolved in chloroform (CHCl3). The reaction system was stirred at room temperature (rt) for 20 min. The solvent was removed by rotary evaporation, and the solution was purified by dry column chromatography (eluents were methanol and dichloromethane, with a volume ratio of methanol to dichloromethane of 1:10) to obtain a white solid L7 (melting point: 190.0-191.6 ℃; overall yield 47%, >20:1 dr).

[0113] The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 H NMR (400 MHz, CD3OD) δ 8.37 (d, J= 7.9 Hz, 2H), 8.02 (t, J = 7.8 Hz, 2H), 7.83 (d, J = 7.6 Hz, 2H), 7.35 (d, J= 8.6 Hz, 4H), 7.16 – 7.10 (m, 6H), 7.06 – 6.80 (m 8H), 6.83 (s, 2H), 4.93 –4.91 (m, 2H), 4.67 (td, J = 8.6, 5.6 Hz, 2H), 3.37 –3.32 (m, 1H), 3.30 – 3.25(m, 1H), 2.91 (dt, J = 14.0, 10.5 Hz, 2H), 2.24 – 2.13 (m, 4H), 2.08 – 1.99 (m, 2H), 1.91 – 1.81 (m, 2H), 1.67 – 1.55 (m, 6H). 13 C NMR (101 MHz, CD3OD) δ169.9, 156.5, 151.8, 140.6, 140.1, 139.5, 135.2, 129.6, 129.1, 128.5, 128.4,127.6, 123.2, 122.4, 94.8, 86.9, 78.7, 43.2, 33.8, 32.2, 30.5, 25.6. HRMS(APCI) m / z calcd for C 52 H 49 N6O4 + (M+H) +821.3810, found 821.3806.

[0114] Figure 3 The image shows the 1H NMR spectrum of the long-arm chiral nitride-bipyridine ligand L7.

[0115] Figure 4 The image shows the carbon NMR spectrum of the long-arm chiral nitride-bipyridine ligand L7.

[0116] Example 4

[0117] The only difference from Example 3 is that, in Example 3, only the compound B with hydrogen-based R1 is replaced with equimolar amounts of the corresponding compounds with R1 of Cl, F, and methyl (corresponding to L8, L9, and L10 below, respectively), or only the compound B with hydrogen-based R2 is replaced with equimolar amounts of the corresponding compounds with R2 of 3,5-di(trifluoromethyl) and 3,5-dimethyl (corresponding to L11 and L12 below, respectively); the resulting products are designated as L8, L9, L10, L11, and L12, respectively. The structural identification data of the resulting products are as follows:

[0118] The long-arm chiral oxynitride-bipyridine ligand L8 prepared in this embodiment is a white solid with a melting point of 219.5-221.1℃ and an overall yield of 42%; its dr ratio is >20:1. The NMR and high-resolution mass spectrometry results are as follows: 1 H NMR (400 MHz, CD3OD). 1 H NMR (400 MHz, CD3OD) δ 8.42 (t, J = 6.7 Hz, 2H), 8.01 (td, J = 7.9,3.3 Hz, 2H), 7.82 (d, J = 7.5 Hz, 2H), 7.29 (d, J = 7.7 Hz, 4H), 6.92 – 6.77(m, 6H), 6.58 – 6.39 (m, 6H), 4.93 (s, 2H), 4.66 (td, J = 8.5, 5.5 Hz, 2H), 3.31 (d, J = 4.9 Hz, 1H), 3.28 (s, 1H), 2.90 (dt, J = 13.9, 10.4 Hz, 2H),2.24 – 2.12 (m, 4H), 2.07 – 1.98 (m, 2H), 1.95 – 1.81 (m, 14H), 1.69 – 1.53 (m, 6H). 13C NMR (101 MHz, CD3OD) δ 169.8, 156.5, 151.8, 140.4, 140.3, 139.5,138.9, 134.9, 129.8, 129.2, 128.4, 125.3, 123.2, 122.1, 94.8, 86.8, 78.7,43.2, 33.8, 32.2, 30.5, 25.6, 21.4, 21.3. HRMS (APCI) m / z calcd for C 56 H 57 N6O4 + (M+H) + 877.4436, found 877.4431.

[0119] The long-arm chiral oxynitride-bipyridine ligand L9 prepared in this embodiment is a white solid with a melting point of 209.7-211.3℃; overall yield 48%; >20:1 dr; the NMR and high-resolution mass spectrometry results are as follows: 1 H NMR (400 MHz, CD3OD)δ 8.34 (d, J = 7.9 Hz, 2H), 7.99 (t, J = 7.8 Hz, 2H), 7.82 (dd, J = 7.8, 2.8Hz, 2H), 7.35 (d, J = 8.5 Hz, 4H), 7.12 – 6.81 (m, 14H), 4.90 (d, J = 6.4 Hz, 2H), 4.66 (td, J = 8.6, 5.6 Hz, 2H), 3.31 (d, J = 5.6 Hz, 1H), 3.28 (d, J =1.6 Hz, 1H), 2.90 (dt, J = 14.1, 10.4 Hz, 2H), 2.24 – 2.10 (m, 4H), 2.06 –1.94 (m, 2H), 1.90 – 1.79 (m, 2H), 1.67 – 1.52 (m, 6H). 13 C NMR (101 MHz, CD3OD) δ 169.9, 156.4, 151.7, 139.50, 138.9, 138.3, 135.5, 134.4, 129.7, 129.1, 128.9, 128.3, 123.2, 122.2, 94.8, 86.7, 78.7, 43.2, 33.8, 32.2, 30.5,25.6. HRMS (APCI) m / z calcd for C52 H 47 Cl2N6O4 + (M+H) + 890.3030 found 890.3027.

[0120] The long-arm chiral oxynitride-bipyridine ligand L10 prepared in this embodiment is a white solid with a melting point of 222.8-224.4 °C; overall yield 57%; >20:1 dr; and the results of NMR and high-resolution mass spectrometry are as follows: 1 H NMR (400 MHz, CD3OD) δ 8.32 (d, J = 7.9 Hz, 2H), 7.94 (t, J = 7.8 Hz, 2H), 7.76 (d, J = 7.6Hz, 2H), 7.26 (d, J = 8.4 Hz, 4H), 6.88 (ddd, J = 22.4, 8.8, 2.5 Hz, 8H), 6.75 (s, 2H), 6.52 (dd, J = 8.6, 1.9 Hz, 4H), 4.61 (td, J = 8.6, 5.6 Hz, 4H), 3.47 (d, J = 1.8 Hz, 6H), 3.29 – 3.27 (m, 1H), 3.25 – 3.20 (m, 1H), 2.86 (dt,J = 13.9, 10.4 Hz, 2H), 2.20 – 2.06 (m, 4H), 2.02 – 1.92 (m, 2H), 1.84 – 1.75(m, 2H), 1.60 – 1.46 (m, 6H). 13 C NMR (101 MHz, CD3OD) δ 169.9, 160.5, 156.5,151.7, 139.7, 139.50, 134.52, 132.8, 129.1, 128.6, 127.94, 123.2, 122.5,115.0, 94.7, 86.9, 78.7, 55.6, 43.2, 33.7, 32.2, 30.4, 25.6. HRMS (APCI) m / zcalcd for C 54 H 53 N6O6 + (M+H) + 881.4021 found 881.34017.

[0121] The long-arm chiral nitride-bipyridine ligand L11 prepared in this embodiment is a white solid with a melting point of 174.6-176.2 °C and an overall yield of 33%; its dr ratio is >20:1. The NMR and high-resolution mass spectrometry results are as follows: 1 H NMR (400 MHz, CD3OD) δ 8.31 (dd, J = 8.0, 1.0 Hz, 2H), 8.07 – 7.98 (m, 6H), 7.88 – 7.82 (m,4H), 7.70 – 7.65 (m, 4H), 7.63 – 7.57 (m, 4H), 6.96 (s, 2H), 4.90 (s, 2H), 4.69 (q, J = 8.4 Hz, 2H), 3.35 (s, 2H), 2.93 (dt, J = 14.0, 10.5 Hz, 2H), 2.28 – 2.18 (m, 4H), 2.08 (dt, J = 15.0, 6.6 Hz, 2H), 1.98 – 1.91 (m, 2H),1.76 – 1.63 (m, 6H). 13 C NMR (101 MHz, CD3OD) δ 170.0, 156.6, 151.7, 143.5,139.5, 137.0, 136.9, 133.4, 133.1, 129.2, 129.1, 128.2, 123.3, 122.7, 94.9,86.7, 78.7, 47.6, 43.5, 33.8, 32.3, 30.5, 25.6. HRMS (APCI) m / z calcd forC 56 H 45 F 12 N6O4 + (M+H) + 1093.3305, found 1093.2202.

[0122] The long-arm chiral nitride-bipyridine ligand L12 prepared in this embodiment is a white solid with a melting point of 164.5-166.1 °C; overall yield 39%; >20:1 dr; and the results of NMR and high-resolution mass spectrometry are as follows: 1H NMR (400 MHz, CD3OD) δ 8.33 (dd, J = 8.0, 1.0 Hz, 2H), 8.03 (t, J = 7.8 Hz, 2H), 7.83 (dd,J = 7.6, 1.0 Hz, 2H), 7.51 – 7.47 (m, 4H), 7.39 – 7.32 (m, 8H), 7.05 – 6.99 (m, 4H), 6.89 (s, 2H), 4.92 – 4.90 (m, 2H), 4.67 (t, J = 7.3 Hz, 2H), 3.40 –3.33 (m, 2H), 2.92 (dt, J = 14.0, 10.5 Hz, 2H), 2.27 – 2.19 (m, 4H), 2.14 –2.06 (m, 2H), 1.96 – 1.90 (m, 2H), 1.75 – 1.65 (m, 6H). 13 C NMR (101 MHz, CD3OD) δ 169.9, 156.6, 151.8, 139.5, 139.2, 135.4, 129.6, 129.5, 129.0,128.5, 123.3, 122.5, 116.5, 116.3, 94.8, 86.9, 78.8, 43.3, 33.8, 32.3, 30.5,25.6. HRMS (APCI) m / z calcd for C 52 H 47 F2N6O4 + (M+H) + 857.3621, found 857.3619.

[0123] Example 5

[0124] The only difference from Example 3 is that, while changing m=0 to m=1, the hydrogen-based compound B (R1) in the raw materials of Example 3 was replaced with equimolar amounts of compounds with R1 of H, Cl, F, and methyl groups respectively (corresponding to L13, L14, L15, and L16 below), or the hydrogen-based compound B (R2) in the raw materials of Example 3 was replaced with equimolar amounts of compounds with R2 of 3,5-di(trifluoromethyl) and 3,5-dimethyl groups respectively (corresponding to L17 and L18 below). The resulting products are designated as L13, L14, L15, L16, L17, and L18, respectively. The structural identification data of the resulting products are as follows:

[0125] The long-arm chiral oxynitride-bipyridine ligand L13 prepared in this embodiment is a white solid with a melting point of 192.4-194.0 °C and an overall yield of 40%; >20:1 dr. 1 H NMR (400 MHz, CD3OD) δ 8.44 (dd, J = 7.9, 3.4Hz, 2H), 7.98 (td, J = 7.8, 2.2 Hz, 2H), 7.74 (dd, J = 7.5, 2.2 Hz, 2H), 7.37(d, J = 8.1 Hz, 4H), 7.12 – 7.02 (m, 14H), 6.93 (s, 2H), 4.87 – 4.80 (m, 2H), 3.95 (dt, J = 11.7, 5.3 Hz, 2H), 3.46 – 3.36 (m, 2H), 2.61 – 2.49 (m, 2H),2.42 – 2.26 (m, 4H), 1.86 – 1.65 (m, 6H), 1.46 (q, J = 14.0, 13.1 Hz, 4H), 1.30 (d, J = 12.5 Hz, 2H), 1.24 – 1.15 (m, 2H). 13 C NMR (101 MHz, CD3OD) δ170.89, 156.5, 152.5, 140.5, 140.1, 139.3, 135.3, 129.7, 128.5, 128.40,127.6, 123.0 122.8, 85.7, 85.3, 77.3, 37.0, 28.7, 25.8, 25.4, 25.1, 21.1.

[0126] Figure 5 The 1H NMR spectrum of the long-arm chiral nitride-bipyridine ligand L13 is shown.

[0127] Figure 6 The image shows the carbon NMR spectrum of the long-arm chiral nitride-bipyridine ligand L13.

[0128] The long-arm chiral oxynitride-bipyridine ligand L14 prepared in this embodiment is a white solid with a melting point of 189.5-191.1 °C and an overall yield of 40%; its dr ratio is >20:1. The NMR and high-resolution mass spectrometry results are as follows: 1H NMR (400 MHz, CD3OD) δ 8.46 (d, J = 7.9 Hz, 2H), 7.99 (t, J = 7.5 Hz, 2H), 7.72 (d, J = 7.5Hz, 2H), 7.31 (d, J = 8.4 Hz, 4H), 6.97 – 6.89 (m, 6H), 6.61 (d, J = 7.1 Hz, 4H), 6.51 (d, J = 7.9 Hz, 2H), 4.86 – 4.82 (m, 2H), 3.95 (dt, J = 11.7, 5.4Hz, 2H), 3.44 – 3.35 (m, 2H), 2.60 – 2.49 (m, 2H), 2.36 (ddd, J = 18.8, 12.6,6.2 Hz, 4H), 1.94 – 1.83 (d, J = 8.8 Hz, 14H), 1.83 – 1.72 (m, 4H), 1.58 –1.42 (m, 4H), 1.41 – 1.29 (m, 2H), 1.26 – 1.18 (m, 2H). 13 C NMR (101 MHz, CD3OD) δ 170.8, 156.6, 152.6, 140.6, 140.5, 139.3, 139.0, 135.1, 129.8,128.6, 128.4, 125.4, 122.9, 122.8, 85.7, 85.3, 77.33, 37.0, 28.8, 25.9, 25.5,25.1, 21.3, 21.2. HRMS (APCI) m / z calcd for C 58 H 61 N6O4 + (M+H) + 905.4749, found905.4744.

[0129] The long-arm chiral oxynitride-bipyridine ligand L15 prepared in this embodiment is a white solid with a melting point of 208.5-210.1 °C and an overall yield of 35%; its dr ratio is >20:1. The NMR and high-resolution mass spectrometry results are as follows: 1H NMR (400 MHz, CD3OD) δ 8.39 (d, J = 7.9 Hz, 2H), 7.95 (t, J = 7.8 Hz, 2H), 7.72 (d, J = 7.6Hz, 2H), 7.36 (d, J = 8.8 Hz, 4H), 7.09 – 6.86 (m, 14H), 4.86 – 4.81 (m, 2H), 3.94 (dt, J = 11.6, 5.3 Hz, 2H), 3.43 – 3.34 (m, 2H), 2.64 – 2.48 (m, 2H), 2.33 (ddd, J = 25.8, 13.0, 6.3 Hz, 4H), 1.83 (d, J = 13.9 Hz, 2H), 1.79 –1.66 (m, 4H), 1.55 – 1.39 (m, 4H), 1.37 – 1.25 (m, 2H), 1.22 – 1.15 (m, 2H). 13 C NMR (101 MHz, CD3OD) δ 170.9, 156.5, 152.5, 139.3, 139.0, 138.4, 135.7,134.4, 129.7, 128.9, 128.6, 128.3, 122.8, 85.7, 85.1, 77.3, 37.0, 31.15,28.8, 25.8, 25.4, 25.1, 21.1. HRMS (APCI) m / z calcd for C 54 H 51 Cl2N6O4 + (M+H) + 917.3343, found 917.3347.

[0130] The long-arm chiral nitride-bipyridine ligand L16 prepared in this embodiment is a white solid with a melting point of 206.6-208.2 °C and an overall yield of 44%; its dr ratio is >20:1. The NMR and high-resolution mass spectrometry results are as follows: 1H NMR (400 MHz, CD3OD) δ 8.40 (dd, J = 8.1, 3.0 Hz, 2H), 7.92 (q, J = 7.6 Hz, 2H), 7.69 (d, J= 7.5 Hz, 2H), 7.32 (dd, J = 8.9, 2.3 Hz, 4H), 7.10 – 6.85 (m, 10H), 6.64 –6.47 (m, 4H), 3.93 (dt, J = 11.7, 5.3 Hz, 2H), 3.56 – 3.33 (m, 8H), 2.52 (dt,J = 12.8, 6.6 Hz, 2H), 2.412.20 (m, 4H), 1.91 – 1.64 (m, 6H), 1.46 (d, J =13.8 Hz, 4H), 1.37 – 1.02 (m, 6H). 13 C NMR (101 MHz, CD3OD) δ 170.98, 160.55,156.59, 152.57, 139.85, 139.32, 134.71, 132.81, 128.67, 127.97, 123.20,122.92, 115.12, 85.73, 85.41, 77.36, 37.04, 28.77, 25.88, 25.48, 25.13,21.14. HRMS (APCI) m / z calcd for C 56 H 57 N6O6 + (M+H) + 909.4334, found 909.4330.

[0131] The long-arm chiral nitride-bipyridine ligand L17 prepared in this embodiment is a white solid with a melting point of 194.9-196.5 °C and an overall yield of 32%; its dr ratio is >20:1. The NMR and high-resolution mass spectrometry results are as follows: 1H NMR (400 MHz, CD3OD) δ 8.44 – 8.36 (m, 2H), 8.00 (dd, J = 9.0, 6.2 Hz, 2H), 7.75 (dd, J =12.4, 7.7 Hz, 3H), 7.60 (d, J = 4.8 Hz, 3H), 7.58 – 7.46 (m, 6H), 7.15 (t, J= 6.9 Hz, 4H), 7.03 – 6.98 (m, 2H), 4.84 (s, 2H), 3.96 (dd, J = 12.7, 5.6 Hz,2H), 3.39 (s, 2H), 2.65 – 2.47 (m, 2H), 2.42 – 2.28 (m, 4H), 1.93 – 1.70 (m,7H), 1.65 – 1.31 (m, 7H), 1.28 – 1.20 (m, 2H). 13 C NMR (101 MHz, CD3OD) δ171.0, 156.5, 152.4, 142.9, 139.4, 137.2, 136.0, 133.1, 132.8, 128.7, 127.7,125.8, 123.0, 122.7, 121.8, 85.8, 85.1, 77.3, 37.1, 28.8, 25.9, 25.4, 25.2,21.2, 9.8. HRMS (APCI) m / z calcd for C 58 H 49 F 12 N6O4 + (M+H) + 1121.3618 found 1121.3616.

[0132] The long-arm chiral oxynitride-bipyridine ligand L18 prepared in this embodiment is a white solid with a melting point of 203.9-205.5 °C and an overall yield of 35%; its dr ratio is >20:1. The NMR and high-resolution mass spectrometry results are as follows: 1H NMR (400 MHz, CD3OD) δ 8.41 (dd, J = 8.0, 1.0 Hz, 2H), 8.02 (t, J = 7.8 Hz, 2H), 7.74 (dd,J = 7.6, 1.0 Hz, 2H), 7.42 – 7.38 (m, 4H), 7.21 – 7.13 (m, 8H), 6.98 – 6.91 (m, 6H), 4.83 (dd, J = 10.3, 6.1 Hz, 2H), 3.97 (dt, J = 12.1, 5.3 Hz, 2H), 3.45 – 3.37 (m, 2H), 2.61 – 2.52 (m, 2H), 2.38 (td, J = 12.8, 5.8 Hz, 4H), 1.93 – 1.77 (m, 6H), 1.62 – 1.46 (m, 6H), 1.30 – 1.22 (m, 2H). 13 C NMR (101MHz, CD3OD) δ 171.0, 156.6, 152.6, 139.3, 139.2, 135.4, 129.6, 129.5, 128.5,128.4, 123.1, 122.9, 116.5, 116.3, 85.8, 85.3, 77.3, 37.1, 28.7, 25.9, 25.5,25.2, 21.2. HRMS (APCI) m / z calcd for C 54 H 51 F2N6O4 + (M+H) + 885.3934 found 885.3032.

[0133] Example 6

[0134] To demonstrate the application value of the bipyridine ligand prepared in this invention in asymmetric catalytic reactions, this example uses 3-vinyl-1H-indole (compound 1a, ) and α,β-unsaturated 2-acylimidazole (compound 2a, The addition cyclization reaction of (where R3 is methyl and R4 is phenyl) was used as a template, and ligands L1~L19 (L19 was used for comparative verification, and its structural formula is) was employed. The in-situ formation of a chiral complex with Lewis acid Ni(OTf)2 was verified by catalysis.

[0135] It should be understood that this embodiment is for illustrative purposes only and is not intended to limit the invention. The application of the bipyridine ligand of the present invention is not limited to this specific reaction; it also has potential application as a chiral ligand in other asymmetric catalytic systems.

[0136] The synthetic route and ligand structure used in this embodiment are as follows: Figure 7 As shown.

[0137] Figure 7 The above is a synthetic route diagram of the asymmetric catalytic reaction of Example 6 of the present invention and the structural formulas of ligands L1 to L19.

[0138] The specific reaction process is as follows: Compound 1a, Compound 2a, Ni(OTf)2, oxynitride-bipyridine ligand, and solvent were mixed and reacted at room temperature for 24 h. The yield was calculated, and the product (compound 3a) was determined by HPLC. The ee value (Chiralpak ADH column, 254 nm, hexane / isopropanol = 70:30, flow rate 1.0 mL / min, column temperature 40 ℃).

[0139] Ten sets of experiments were conducted. In the first to ninth sets of experiments, the nitride-bipyridine ligands used were L1, L7, L13, L19, L2, L3, L4, L5, and L6, respectively. The amount of compound 1a was 0.24 mmol, the amount of compound 2a was 0.20 mmol, the amount of Ni(OTf)2 was 10 mol% of compound 2a, and the amount of nitride-bipyridine ligand was 12 mol% of compound 2a. The solvent used in all experiments was 1 mL of dichloromethane (DCM).

[0140] The other conditions for the 10th experiment were the same as those for the 1st experiment, except that the reaction temperature was lowered from room temperature to 0℃.

[0141] The product yields and ee values ​​for each group of experiments are shown in Table 1.

[0142] Table 1. Product yield and ee value (enantiomer excess value)

[0143] Serial Number ligands solvent Reaction time (h) Yield (%) ee value (%) 1 L1 DCM 24 72 81 2 L7 DCM 24 90 52 3 L19 DCM 24 87 32 4 L13 DCM 24 89 53 5 L2 DCM 24 65 61 6 L3 DCM 24 70 72 7 L4 DCM 24 64 74 8 L5 DCM 24 72 80 9 L6 DCM 24 75 80 10 L1 DCM 24 67 99

[0144] As can be seen from Table 1, in this reaction system, the bipyridine-bridged chiral dioxoligand of the present invention can achieve good yields and moderate to excellent ee values.

[0145] The compound prepared in the 10th group of experiments in Example 6 was (1-methyl-1H-imidazol-2-yl)((1R,2S)-1-phenyl-2,3,9,9a-tetrahydro-1H-carbazole-2-yl) methyl ketone (3a), and its structural identification data are as follows: yellow solid, melting point: 91.9-93.5 °C; overall yield 67%. The results of high-performance liquid chromatography, optical rotation, nuclear magnetic resonance, and high-resolution mass spectrometry are as follows: HPLC: 99% ee (Chiralpak ADH column, λ = 254 nm, n-hexane / i-PrOH = 70:30, flow rate: 1.0 mL / min, 40 °C, tr (major) = 9.64 min, tr (minor) = 11.94 min); [α] D 20 = +51.6 (c = 0.2, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.30 (dd, J = 7.3, 1.2 Hz,1H), 7.24 – 7.21 (m, 2H), 7.14 – 6.99 (m, 6H), 6.83 (d, J = 0.9 Hz, 1H), 6.75(td, J = 7.5, 1.0 Hz, 1H), 6.60 (d, J = 7.8 Hz, 1H), 5.94 (q, J = 3.7 Hz,1H), 4.98 – 4.89 (m, 1H), 4.59 (dd, J = 11.6, 9.9 Hz, 1H), 3.64 (s, 3H), 3.42(td, J = 11.1, 6.4 Hz, 1H), 2.76 – 2.55 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ195.73, 152.84, 144.43, 142.31, 139.32, 129.52, 128.92, 128.24, 128.14,127.53, 127.00, 126.55, 120.41, 119.48, 114.87, 111.25, 64.45, 52.75, 44.71,36.03, 35.76, 29.81.HRMS (ESI, m / z) calcd for C 23 H 22 N3O + (M+H) +: 356.1757, found 356.1751.

[0146] Example 7

[0147] This embodiment examines the universality of the ligands. All ligands used are L1, and the experimental conditions are the same as those in the 10th group of experiments in Example 6. The only difference is that compound 2a, where R4 is a 4-bromosubstituted phenyl compound, was replaced with equimolar amounts of the corresponding compounds with R4 of 4-bromosubstituted phenyl, 3,4-dimethylsubstituted phenyl, 4-methylsubstituted phenyl, and 2-thienyl substituted phenyl compounds, respectively. The resulting products are designated as 3b, 3c, 3d, and 3e, respectively. Details are as follows:

[0148] The method for preparing 3b in this embodiment differs from that in Example 6 only in that R4 in compound 2a is a 4-bromosubstituted phenyl compound, and the product obtained is compound ((1R,2S)-1-(4-bromophenyl)-2,3,9,9a-tetrahydro-1H-carbazole-2-yl)(1-methyl-1H-imidazol-2-yl) methyl ketone (3b).

[0149] In this embodiment, 3b was prepared as a yellow solid with a melting point of 100.8-102.4 °C and an overall yield of 70%. The results of high-performance liquid chromatography (HPLC), optical rotation analysis (IPA), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HPLC) are as follows: HPLC: 99% ee (Chiralpak ADH column, λ = 254 nm, n-hexane / i-PrOH = 70:30, flow rate: 1.0 mL / min, 40 °C, tr (major) = 12.58 min, tr (minor) = 15.37 min); [α] D 20 = +44.3 (c = 0.2, CH2Cl2). 1H NMR (400 MHz, CDCl3) δ 7.30 (dd, J = 7.7, 1.2 Hz, 1H), 7.25 – 7.22 (m, 2H), 7.19– 7.05 (m, 4H), 7.02 (td, J = 7.7, 1.3 Hz, 1H), 6.90 (d, J = 0.9 Hz, 1H), 6.75 (td, J = 7.4, 1.0 Hz, 1H), 6.60 (d, J = 7.9 Hz, 1H), 5.91 (q, J = 3.6Hz, 1H), 4.87 (ddt, J = 9.9, 4.7, 3.4 Hz, 1H), 4.58 (dd, J = 11.6, 9.8 Hz,1H), 3.72 (s, 3H), 3.40 (td, J = 11.2, 6.4 Hz, 1H), 2.73 – 2.63 (m, 1H), 2.60– 2.46 (m, 1H). 13 C NMR (101 MHz, CDCl3) δ 195.26, 152.78, 144.15, 141.60,139.43, 131.26, 130.01, 129.74, 129.03, 127.39, 120.46, 120.28, 119.57,114.53, 111.28, 64.51, 52.35, 43.95, 36.05, 35.99. .HRMS (ESI, m / z) calcd forC 23 H 21 BrN3O + (M+H) + : 434.0863, found 434.0858.

[0150] The method for preparing 3c in this embodiment differs from that in Example 6 only in that R4 in compound 2a is 3,4-dimethyl-substituted phenyl, and the product obtained is compound ((1R,2S)-1-(3,4-dimethylphenyl)-2,3,9,9a-tetrahydro-1H-carbazole-2-yl)(1-methyl-1H-imidazol-2-yl) methyl ketone (3c).

[0151] In this embodiment, 3c was prepared as a yellow solid with a melting point of 96.5-98.13 °C and an overall yield of 61%. The results of high-performance liquid chromatography (HPLC), optical rotation analysis (IPA), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HPLC) are as follows: HPLC: 99% ee (Chiralpak ADH column, λ = 254 nm, n-hexane / i-PrOH = 70:30, flow rate: 1.0 mL / min, 40 °C, tr (major) = 8.48 min, tr (minor) = 9.58 min); [α] D 20 = +37.68 (c = 0.2, CH2Cl2). 1 H NMR(400 MHz, CDCl3) δ 7.31 – 7.28 (m, 1H), 7.10 (d, J = 0.9 Hz, 1H), 7.08 – 6.99(m, 3H), 6.95 (dd, J = 7.7, 2.0 Hz, 1H), 6.88 – 6.83 (m, 2H), 6.74 (td, J =7.5, 1.0 Hz, 1H), 6.59 (d, J = 7.9 Hz, 1H), 5.93 (q, J = 3.6 Hz, 1H), 4.90 (ddt, J = 9.9, 4.6, 3.5 Hz, 1H), 4.58 (dd, J = 11.6, 9.9 Hz, 1H), 3.65 (s,3H), 3.36 (dt, J = 11.2, 5.6 Hz, 1H), 2.73 – 2.52 (m, 2H), 2.11 (s, 6H). 13 CNMR (101 MHz, CDCl3) δ 195.98, 152.85, 144.52, 139.74, 139.25, 136.22,134.55, 129.58, 129.43, 129.34, 128.86, 127.59, 126.85, 125.41, 120.37,119.43, 115.05, 111.20, 64.54, 52.69, 44.21, 36.33, 35.76, 19.67, 19.35..HRMS (ESI, m / z) calcd for C 25 H 26 N3O + (M+H) +: 384.2070, found 384.2074.

[0152] The method for preparing 3d in this embodiment differs from that in Example 6 only in that R4 in compound 2a is a 4-methyl-substituted phenyl compound, and the product obtained is compound (1-methyl-1H-imidazol-2-yl)((1R,2S)-1-(p-tolyl)-2,3,9,9a-tetrahydro-1H-carbazole-2-yl) methyl ketone (3d).

[0153] In this embodiment, a 3d: yellow solid with a melting point of 98.3-99.9 °C was prepared; the overall yield was 65%. The results of high-performance liquid chromatography (HPLC), optical rotation analysis (OPC), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HPLC) are as follows: HPLC: 98% ee (Chiralpak ADH column, λ = 254 nm, n-hexane / i-PrOH = 70:30, flow rate: 1.0 mL / min, 40 °C, tr (major) = 8.03 min, tr (minor) = 12.97 min); [α] D 20 = +30.4 (c = 0.1, CH2Cl2). 1 H NMR (400MHz, CDCl3) δ 7.33 – 7.29 (m, 2H), 7.12 – 7.08 (m, 2H), 7.04 – 7.00 (m, 2H), 6.96 – 6.91 (m, 2H), 6.85 (d, J = 0.9 Hz, 1H), 6.75 (td, J = 7.5, 1.0 Hz,1H), 6.61 (d, J = 7.9 Hz, 1H), 5.94 (q, J = 3.6 Hz, 1H), 4.93 (dq, J = 8.1,3.8 Hz, 1H), 4.64 (dd, J = 11.5, 9.8 Hz, 1H), 3.83 – 3.76 (m, 1H), 3.61 (s,3H), 2.53 – 2.41 (m, 2H), 2.37 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 195.75,152.80, 144.43, 139.39, 129.54, 128.92, 127.57, 127.01, 126.16, 126.08,120.39, 119.48, 115.08, 111.28, 64.83, 52.47, 35.71, 19.83. .HRMS (ESI, m / z)calcd for C 24 H 24 N3O + (M+H) + : 370.1914, found 370.1910.

[0154] The method for preparing 3e in this embodiment differs from that in Example 6 only in that R4 in compound 2a is substituted with 2-thienyl, and the product obtained is compound (1-methyl-1H-imidazol-2-yl)((1S,2S)-1-(thien-2-yl)-2,3,9,9a-tetrahydro-1H-carbazole-2-yl) methyl ketone (3e).

[0155] In this embodiment, 3e was prepared as a yellow solid with a melting point of 93.2-94.8 °C and an overall yield of 65%. The results of high-performance liquid chromatography (HPLC), optical rotation analysis (IPA), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HPLC-MS) are as follows: HPLC: 98% ee (Chiralpak ADH column, λ = 254 nm, n-hexane / i-PrOH = 70:30, flow rate: 1.0 mL / min, 40 °C, tr (major) = 10.79 min, tr (minor) = 11.67 min); [α] D 20 = +45.6 (c = 0.1, CH2Cl2). 1H NMR (400 MHz, CDCl3) δ 7.30 (dd, J = 7.5, 1.3 Hz, 1H), 7.13 – 6.98 (m, 3H), 6.96 (dd, J =5.0, 1.2 Hz, 1H), 6.90 (s, 1H), 6.80 (dd, J = 3.6, 1.2 Hz, 1H), 6.77 – 6.71(m, 2H), 6.60 (d, J = 7.7 Hz, 1H), 5.91 (q, J = 3.6 Hz, 1H), 4.90 (ddt, J =9.9, 4.6, 3.4 Hz, 1H), 4.48 (dd, J = 11.4, 9.9 Hz, 1H), 3.79 (s, 4H), 2.84 –2.79 (m, 1H), 2.77 – 2.69 (m, 1H). 13 C NMR (101 MHz, CDCl3) δ 195.08, 152.77,145.81, 144.21, 139.32, 129.67, 129.02, 127.38, 127.21, 126.32, 124.80,123.26, 120.45, 119.54, 114.29, 111.28, 64.25, 54.12, 39.18, 36.66, 36.03..HRMS (ESI, m / z) calcd for C 21 H 20 N3OS + (M+H) + : 362.1322, found 362.1315.

[0156] The results of Example 7 show that the bipyridine-bridged chiral dioxoligand substrates provided by the present invention have broad adaptability and good compatibility with various substituents.

[0157] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A class of chiral dinitroxide ligands based on bipyridine bridging, characterized in that, The bipyridine-bridged chiral bis(oxynitride) ligand is a spirocyclic chiral oxynitride-bipyridine ligand or a long-arm chiral oxynitride-bipyridine ligand; The spirocyclic chiral oxynitride-bipyridine ligand has the structure shown in Formula I: ； In Formula I, Ar is a phenyl, an alkyl-substituted phenyl, a cycloalkyl-substituted phenyl, or a halophenyl; The long-arm chiral oxynitride-bipyridine ligand has a structure as shown in Formula II: ； In Formula II, R1 and R2 are independently hydrogen, alkyl, halogen substituent or haloalkyl, and m is 1 or 2.

2. The chiral dinitroxide ligand based on bipyridine bridging according to claim 1, characterized in that, In Formula I, the alkyl-substituted phenyl group has 1 to 5 carbon atoms in the alkyl group; the cycloalkyl-substituted phenyl group has 3 to 6 carbon atoms in the cycloalkyl group; and the halophenyl group is a fluorophenyl or a chlorophenyl. In Formula II, the alkyl group has 1 to 5 carbon atoms; the halogen substituent is fluorine or chlorine; and the haloalkyl group is trifluoromethyl.

3. The chiral dinitroxide ligand based on bipyridine bridging according to claim 1, characterized in that, The spirocyclic chiral nitride-bipyridine ligand has the structure shown in any one of formulas L1 to L6: 。 4. The chiral dinitroxide ligand based on bipyridine bridging according to claim 1, characterized in that, The long-arm chiral nitride-bipyridine ligand has the structure shown in any one of formulas L7 to L18: 。 5. A method for preparing a chiral dinitroxide ligand based on bipyridine bridging as described in any one of claims 1-4, characterized in that, Includes the following steps: Using compound C or compound D as a precursor and m-chloroperoxybenzoic acid as an oxidant, a nitrogen oxidation reaction is carried out in a solvent to obtain the chiral bis(nitrogen oxide) ligand based on bipyridine bridging. When compound C is used as a raw material, the product has the structure shown in Formula I; When compound D is used as a raw material, the product has the structure shown in Formula II; The structure of compound C is shown in formula C, and the structure of compound D is shown in formula D: 、 。 6. The preparation method according to claim 5, characterized in that, The molar ratio of the precursor to m-chloroperoxybenzoic acid is 1:2~3; the solvent is chloroform; the concentration of the precursor in the solvent is 0.1M~0.2M; and the time for the nitrogen oxidation reaction is 20min~60min.

7. The preparation method according to claim 5, characterized in that, The preparation method of compound C includes the following steps: Compound A and 2,2'-bipyridine-6,6'-dicarboxaldehyde were mixed in an alcohol solvent and subjected to a bridging reaction to obtain compound C. The molar ratio of compound A to bipyridine-6,6'-dicarboxaldehyde is 2-3:1; the alcohol solvent is ethanol; the concentration of compound A in the alcohol solvent is 0.1M-0.2M; the bridging reaction is carried out at 80℃-85℃ for 6h-24h; compound A is shown below: 。 8. The preparation method according to claim 5, characterized in that, The preparation method of compound D includes the following steps: Compound B and 2,2'-bipyridine-6,6'-dicarboxaldehyde were mixed in an alcohol solvent and a bridging reaction was carried out to obtain compound D. The molar ratio of compound B to bipyridine-6,6'-dicarboxaldehyde is 2~3:1; the alcohol solvent is ethanol; the concentration of compound B in the alcohol solvent is 0.1M~0.2M; the bridging reaction is carried out at 80℃~85℃ for 6h~24h; compound B is shown below: 。 9. The application of a bipyridine-bridged chiral dioxoligand as described in any one of claims 1-4 in asymmetric catalytic reactions.

10. A method for an asymmetric cycloaddition reaction involving α,β-unsaturated acylimidazolium compounds, characterized in that, Includes the following steps: The 3-vinyl-1H-indole compound, the α,β-unsaturated acylimidazolium compound, the metal Lewis acid, the bipyridine-bridged chiral dioxo-ligand as described in any one of claims 1-4, and the solvent were mixed and subjected to an asymmetric cycloaddition reaction to complete the preparation.

Images