Chiral tridentate P, N, N-ligand as well as preparation method and application thereof

Abstract

The invention provides a preparation method of a novel chiral tridentate P, N, N-ligand based on a cis cyclic 1, 2-amino-phosphine skeleton and an application of the novel chiral tridentate P, N, N-ligand in an asymmetric catalytic reaction. The chiral ligand is prepared by taking cis chiral 2-(diphenylphosphine)-1, 2, 3, 4-tetrahydro-1-naphthylamine and 2-pyridine carbon compound as raw materials and carrying out one-step reaction under the action of a dehydrating agent and under mild conditions. The chiral ligand is stable in property, insensitive to air and humidity and capable of being stored for a long time. The catalyst composed of the chiral tridentate P, N, N-ligand and a Cu metal precursor shows excellent catalytic activity and stereoselectivity in an asymmetric propargyl conversion reaction.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and particularly to a preparation method of a cis-cyclic 1,2-amino-phosphine framework chiral tridentate P,N,N-ligand and its application in Cu-catalyzed asymmetric propargylic transformation reaction. Background Art

[0002] The development of new chiral ligands is the core of asymmetric catalysis research, and is of great significance for solving challenging problems in asymmetric catalysis research and developing new asymmetric catalytic reactions. In the past half century, a large number of chiral ligands have been discovered and developed, which has greatly promoted the development of asymmetric catalysis research. Among them, chiral tridentate P,N,N-ligands have received extensive attention recently due to their simple synthesis and variable structures, and have been widely used in many asymmetric catalysis reactions such as iridium-catalyzed asymmetric hydrogenation, manganese-catalyzed asymmetric hydrogenation, copper-catalyzed asymmetric propargylic transformation, etc. (Wang, H.; Wen, J.; Zhang, X. Chiral Tridentate Ligands in Transition Metal-Catalyzed Asymmetric Hydrogenation, Chem. Rev., 2021, 121(13), 7530-7567).

[0003] Currently, most chiral tridentate P,N,N-ligands are based on 1,3- or 1,4-amino-phosphine frameworks, while 1,2-amino-phosphine frameworks, especially cis-cyclic 1,2-amino-phosphine frameworks with two chiral centers, have not been used in the development of chiral P,N,N-ligands. Since the chiral P,N,N-ligand with a cis-cyclic 1,2-phosphine-amine framework with two chiral centers forms a more favorable chiral environment around the central metal after coordinating with the central metal, it is expected to obtain more excellent catalytic effects in asymmetric catalytic reactions. Therefore, it is of great significance to develop new chiral tridentate P,N,N-ligands based on cis-cyclic 1,2-amino-phosphine frameworks. For this purpose, we developed a new chiral tridentate P,N,N-ligand with a cis-cyclic 1,2-amino-phosphine framework with two chiral centers using chiral 2-(diphenylphosphino)-1,2,3,4-tetrahydro-1-naphthylamine as a raw material and successfully applied it in Cu-catalyzed asymmetric propargylic transformation reaction. Summary of the Invention

[0004] The object of the present invention is to provide a new chiral tridentate P,N,N-ligand based on a cis-cyclic 1,2-amino-phosphine framework. This chiral ligand can be used in Cu-catalyzed asymmetric propargylic transformation reaction and has excellent catalytic activity and stereoselectivity.

[0005] Specifically, the chiral tridentate P,N,N-ligand of the present invention has the (R,S)-I or (S,R)-II structure shown in the following formula:

[0006]

[0007] Among them, (R,S)-I and (S,R)-II are enantiomers; R is hydrogen, C 1 -C 6 a linear or branched alkyl group, C 3 -C 6 a cycloalkyl group, C 6 -C 10 an aryl group or a substituted aryl group; the substituents of the substituted aryl group are selected from C 1 -C 6 an alkyl group, C 1 -C 6 an alkoxy group, a halogen, a nitro group, an ester group or a cyano group, one or more of them; preferably hydrogen, methyl, phenyl.

[0008] To achieve the above object, in the present invention, the preparation method of the chiral tridentate P,N,N-ligand (R,S)-I or (S,R)-II is carried out according to the following reaction route.

[0009]

[0010] In the present invention, the preparation method of the chiral tridentate P,N,N-ligand I includes the following steps:

[0011] Under nitrogen protection, the cis-chiral 2-(diphenylphosphino)-1,2,3,4-tetrahydro-1-naphthylamine (R,S)-III or (S,R)-IV and the 2-pyridinecarbonyl compound V are placed in a reaction flask, a solvent is added, and a dehydrating agent is added in batches with stirring. The reaction solution is heated to reflux, and when TLC detects that the reaction raw materials are basically consumed completely, the reaction solution is concentrated under reduced pressure until the solvent is almost gone, separated by silica gel column chromatography, concentrated under reduced pressure, and dried in vacuo to obtain the chiral tridentate P,N,N-ligand.

[0012] In the present invention, the reaction medium is selected from one or more of methanol, ethanol, tetrahydrofuran, diethyl ether, ethyl acetate, toluene, xylene, dichloromethane, dichloroethane, etc. Preferably, it is toluene.

[0013] The dehydrating agent is selected from one or two or more of anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous calcium chloride, silica gel, activated aluminum oxide, titanium tetraisopropoxide, etc.; preferably a 1:1 mixture of anhydrous magnesium sulfate and activated aluminum oxide.

[0014] The molar ratio of the (R,S)-III or (S,R)-IV to the 2-pyridylcarbonyl compound V is 1:0.5 - 2.5. Preferably, it is 1:1.0 - 1.5; more preferably, it is 1:1.1 - 1.2.

[0015] The weight ratio of the (R,S)-III or (S,R)-IV to the dehydrating agent is 1:1 - 10. Preferably, it is 1:5 - 6.

[0016] In the present invention, for the chiral tridentate P,N,N-ligand, its preferred ligand structure is as follows:

[0017]

[0018] The present invention also relates to the application of the above ligand in the Cu-catalyzed asymmetric propargylic transformation reaction.

[0019] A novel chiral tridentate P,N,N-ligand provided by the present invention can be used in the Cu-catalyzed asymmetric propargylic transformation reaction. Among them, the Cu metal catalyst precursor is selected from one or more of hydrated or anhydrous Cu(OAc) 2 , Cu(OTf) 2 , CuCl, CuI, Cu(CH 3 CN) 4 BF 4 etc. Preferably, it is hydrated Cu(OAc) 2 .

[0020] Advantages of the present invention:

[0021] The chiral tridentate P,N,N-ligand of the present invention has the characteristics of simple preparation method, stable properties, insensitivity to air and humidity, and easy modification of the structure. It shows good reaction activity and enantioselectivity in the Cu-catalyzed asymmetric propargylic transformation reaction. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings forming a part of this specification are used to provide a further understanding of the present invention. The schematic embodiments and descriptions thereof of the present invention are used to explain the present invention and do not constitute an improper limitation of the present invention. Hereinafter, the embodiments of the present invention will be described in detail with reference to the drawings, wherein:

[0023] Figure 1 1H NMR spectrum of the chiral tridentate P,N,N-ligand (R,S)-Ia prepared in Example 1;

[0024] Figure 2 13C NMR spectrum of the chiral tridentate P,N,N-ligand (R,S)-Ia prepared in Example 1;

[0025] Figure 331P NMR spectrum of the chiral tridentate P,N,N-ligand (R,S)-Ia prepared in Example 1 Detailed Description of the Invention

[0026] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. The experimental methods without specific conditions noted in the following embodiments are generally carried out under conventional conditions or according to the conditions recommended by the manufacturer.

[0027] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. The reagents or raw materials used in the present invention can be obtained through conventional channels. Unless otherwise specified, the reagents or raw materials used in the present invention are used in the conventional manner in the art or according to the product instructions. In addition, any methods and materials similar or equivalent to the described content can be applied to the method of the present invention. The preferred implementation methods and materials described herein are only for demonstration purposes. The nuclear magnetic resonance in the embodiments of the present invention is measured by a Bruker 400 nuclear magnetic resonance spectrometer. Unless otherwise specified, all raw materials in the embodiments are known or commercially available compounds.

[0028] Example 1

[0029] The chiral 2-(diphenylphosphino)-1,2,3,4-tetrahydro-1-naphthylamine [(R,S)-III] and 2-pyridinecarboxaldehyde (V-a) were used to prepare the chiral tridentate P,N,N-ligand (R,S)-Ia.

[0030]

[0031] Specific preparation method: Under nitrogen protection, chiral 2-(diphenylphosphino)-1,2,3,4-tetrahydro-1-naphthylamine (R,S)-III (331 mg, 1.0 mmol) (known compound) and 2-pyridinecarboxaldehyde V-a (commercially available product) (128 mg, 1.2 mmol, 1.2 equiv.) were added to a reaction flask, 5.0 mL of anhydrous toluene was added, and the mixture was stirred. A total of 1.655 g of a mixture of activated Al2O3 and MgSO4 (weight ratio 1:1) was added in 5 equal portions. The reaction solution was heated to reflux at 110 °C, and TLC was used to detect the reaction until the raw material (R,S)-III was consumed completely. The dehydrating agent was filtered off, the solvent was removed by reduced pressure concentration, and the product was separated by silica gel column chromatography (petroleum ether / ethyl acetate / triethylamine, 10 / 2 / 0.1, v / v / v). After concentration under reduced pressure and drying under vacuum, 298 mg of white solid (R,S)-Ia was obtained with a yield of 71%. Melting point 108–110 °C. [α] D 20 = 249.0 (c 0.1, CH 2 Cl 2 ). 11H NMR (400 MHz, Chloroform-d) δ 8.59 (d, J = 4.8 Hz, 1H), 8.07 (d, J = 7.9 Hz, 1H), 8.02 (s, 1H), 7.68 (t, J = 7.7 Hz, 1H), 7.58–7.52 (m, 4H), 7.33–7.23 (m, 7H), 7.17–7.15 (m, 2H), 7.09–7.05 (m, 1H), 6.93 (d, J = 7.7 Hz, 1H), 4.53 (t, J = 4.1 Hz, 1H), 3.04–2.87 (m, 3H), 2.47–2.35 (m, 1H), 1.94–1.81 (m, 1H). 13 13C NMR (101 MHz, Chloroform-d) δ 161.0, 154.7, 149.2, 137.5 (d, J C-P = 15.2 Hz), 137.0, 136.5, 136.2 (d, J C-P = 5.0 Hz), 136.1 (d, J C-P = 15.1 Hz), 134.1 (d, J C-P = 20.2 Hz), 133.6 (d, J C-P = 20.4 Hz), 129.7, 129.3 (d, J C-P = 21.5 Hz), 128.7, 128.6, 128.53 (d, J C-P = 5.2 Hz), 128.50, 127.6, 126.1, 124.7, 121.8, 68.0 (d, J C-P = 7.7 Hz), 38.9 (d, J C-P = 9.1 Hz), 29.7 (d, J C-P = 10.7 Hz), 21.4 (d, J C-P = 17.2 Hz). 31 31P NMR (162 MHz, Chloroform-d) δ -13.3. HRMS (ESI): calcd for C 28 H 26 N 2 P [M+H] + : 421.1828, found: 421.1828.

[0032] Stability experiment: (R,S)-Ia was placed in an open environment (an open container in contact with air) for six months, and then detected by NMR. The results showed that the compound structure did not change and the optical rotation detection data did not change.

[0033] Example 2

[0034] Preparation of chiral tridentate P,N,N-ligand (S,R)-IIa from chiral 2-(diphenylphosphino)-1,2,3,4-tetrahydro-1-naphthylamine (S,R)-IV and 2-pyridinecarboxaldehyde V-a

[0035]

[0036] The process and conditions were the same as in Example 1, except that (R,S)-III in Example 1 was replaced with its enantiomer (S,R)-IV (a known compound) in equimolar amounts, and the rest was the same as in Example 1. 235 mg of white solid (S,R)-IIa was obtained in 56% yield. Melting point 108–110 °C. [α] D 20 = -228.0 (c 0.11, CH 2 Cl 2 ). 1 1H NMR (400 MHz, Chloroform-d) δ 8.58 (d, J = 4.8 Hz, 1H), 8.07 (d, J = 7.9 Hz, 1H), 8.02 (s, 1H), 7.67 (t, J = 7.7 Hz, 1H), 7.57–7.52 (m, 4H), 7.34–7.25 (m, 7H), 7.17–7.15 (m, 2H), 7.08–7.05 (m, 1H), 6.93 (d, J = 7.7 Hz, 1H), 4.52 (t, J = 4.1 Hz, 1H), 3.05–2.89 (m, 3H), 2.47–2.36 (m, 1H), 1.95–1.81 (m, 1H). 13 13C NMR (101 MHz, Chloroform-d) δ 161.0, 154.6, 149.1, 137.6 (d, JC-P = 15.2 Hz), 137.2, 136.6, 136.2 (d, JC-P = 5.0 Hz), 136.0 (d, JC-P = 15.1 Hz), 134.2 (d, JC-P = 20.2 Hz), 133.5 (d, JC-P = 20.4 Hz), 129.8, 129.4 (d, JC-P = 21.5 Hz), 128.8, 128.6, 128.55 (d, JC-P = 5.2 Hz), 128.51, 127.7, 126.2, 124.6, 121.9, 68.1 (d, JC-P = 7.7 Hz), 38.9 (d, JC-P = 9.1 Hz), 29.8 (d, JC-P = 10.7 Hz), 21.5 (d, JC-P = 17.2 Hz). 31 31P NMR (162 MHz, Chloroform-d) δ -13.3. HRMS (ESI): calcd for C28 H 26 N 2 P[M+H] + :421.1828, found: 421.1832.

[0037] Example 3

[0038] Chiral 2-(diphenylphosphino)-1,2,3,4-tetrahydro-1-naphthylamine (R,S)-III and 2-pyridyl benzophenone V-b were used to prepare chiral tridentate P,N,N-ligand (R,S)-Ib.

[0039]

[0040] The procedure and conditions were the same as in Example 1, except that 2-pyridinecarboxaldehyde V-a in Example 1 was replaced with 2-pyridyl benzophenone V-b (commercially available product) in an equimolar amount, and the rest was the same as in Example 1. 408 mg of white solid (R,S)-Ib was obtained in 82% yield. Melting point 112–114 °C. [α] D 20 = 176.0 (c 0.1, CH 2 Cl 2 ). 1 H NMR (400 MHz, Chloroform-d) δ 8.71 (d, J = 4.8 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.96–7.74 (m, 4H), 7.53–7.42 (m, 7H), 7.17–7.09 (m, 1H), 6.92 (d, J = 7.7 Hz, 1H), 4.50 (t, J = 4.1 Hz, 1H), 3.06–2.89 (m, 3H), 2.51–2.37 (m, 1H), 1.99–1.86 (m, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 164.6, 149.8, 149.7, 138.5, 138.1, 138.0, 137.7, 136.2, 136.1, 136.1, 134.3, 134.0, 133.5, 130.0, 129.7, 128.9, 128.8, 128.5, 128.4, 127.7, 126.2, 124.8, 121.0, 68.5, 38.6, 29.8, 21.4. 31 P NMR (162 MHz, Chloroform-d) δ -16.7. HRMS (ESI): calcd for C 34 H 30 N 2 P[M+H] +: 497.2147, found: 497.2140.

[0041] Example 4

[0042] The procedure and conditions were the same as in Example 1, except that the solvent in Example 1 - anhydrous toluene was replaced with methanol in an equal volume, and the mixture was heated to reflux at 65 °C. The rest was the same as in Example 1, and 166 mg of (R,S)-Ia was obtained with a yield of 40%.

[0043] Example 5

[0044] The procedure and conditions were the same as in Example 1, except that the solvent in Example 1 - anhydrous toluene was replaced with ethanol in an equal volume, and the mixture was heated to reflux at 78 °C. The rest was the same as in Example 1, and 189 mg of (R,S)-Ia was obtained with a yield of 45%.

[0045] Example 6

[0046] The procedure and conditions were the same as in Example 1, except that the solvent in Example 1 - anhydrous toluene was replaced with dichloroethane in an equal volume, and the mixture was heated to reflux at 84 °C. The rest was the same as in Example 1, and 207 mg of (R,S)-Ia was obtained with a yield of 49%.

[0047] Example 7

[0048] The procedure and conditions were the same as in Example 1, except that the solvent in Example 1 - anhydrous toluene was replaced with tetrahydrofuran in an equal volume, and the mixture was heated to reflux at 66 °C. The rest was the same as in Example 1, and 125 mg of (R,S)-Ia was obtained with a yield of 30%.

[0049] Example 8

[0050] The procedure and conditions were the same as in Example 1, except that the dehydrating agent in Example 1 - the mixture of activated Al 2 O 3 and MgSO 4 (weight ratio 1:1) was replaced with an equal mass of activated Al 2 O 3 , and the rest was the same as in Example 1. 87 mg of (R,S)-Ia was obtained with a yield of 21%.

[0051] Example 9

[0052] The procedure and conditions were the same as in Example 1, except that the dehydrating agent in Example 1 - the mixture of activated Al 2 O 3 and MgSO 4 (weight ratio 1:1) was replaced with an equal mass of MgSO 4, the rest is the same as in Example 1, to obtain 98 mg of (R,S)-Ia, with a yield of 23%.

[0053] Example 10

[0054] The process and conditions are the same as in Example 1, the difference being that the dehydrating agent - activated Al 2 O 3 and MgSO 4 mixture (weight ratio 1:1) in Example 1 was replaced with an equal mass of titanium tetraisopropoxide. The rest is the same as in Example 1, to obtain 178 mg of (R,S)-Ia, with a yield of 42%.

[0055] Example 11

[0056] The process and conditions are the same as in Example 1, the difference being that the amount of the dehydrating agent - activated Al 2 O 3 and MgSO 4 mixture (weight ratio 1:1) in Example 1 was halved. The rest is the same as in Example 1, to obtain 113 mg of (R,S)-Ia, with a yield of 27%.

[0057] Example 12

[0058] The process and conditions are the same as in Example 1, the difference being that the amount of the dehydrating agent - activated Al 2 O 3 and MgSO 4 mixture (weight ratio 1:1) in Example 1 was doubled. The rest is the same as in Example 1, to obtain 201 mg of (R,S)-Ia, with a yield of 48%.

[0059] Example 13

[0060] The process and conditions are the same as in Example 1, the difference being that the amount of 2-pyridinecarboxaldehyde V-a in Example 1 was reduced to 1.0 mmol. The rest is the same as in Example 1, to obtain 221 mg of (R,S)-Ia, with a yield of 53%.

[0061] Example 14

[0062] The process and conditions are the same as in Example 1, the difference being that the amount of 2-pyridinecarboxaldehyde V-a in Example 1 was increased to 1.5 mmol. The rest is the same as in Example 1, to obtain 269 mg of (R,S)-Ia, with a yield of 64%.

[0063] Example 15

[0064]

[0065] Under nitrogen protection, CuCl (0.015 mmol, 5.0 mol%), (R,S)-Ia (0.0165 mmol, 5.5 mol%) were dissolved in methanol (1.0 mL), stirred at room temperature (25 °C) for 1 hour, then N-methylaniline (0.3 mmol), 1-phenyl-2-propynyl acetate S-2 (known compound) (0.36 mmol), Et3N (0.36 mmol), and methanol (2.0 mL) were added, and the reaction was continued at 0 °C for 24 hours. After removing the solvent, the product N-methyl-N-(1-phenylprop-2-yn-1-yl)aniline (known compound) 62 mg was obtained by silica gel column chromatography (petroleum ether / ethyl acetate, 10:1, v / v) with a yield of 94% and an enantioselectivity of 96% ee by chiral HPLC analysis (HPLC conditions: chiralcel OD-H, 40 °C, 254 nm, n-hexane / 2-propanol = 95 / 5, flow rate = 0.8 mL / min, major enantiomer: t1 = 5.59 min; minor enantiomer: t2 = 6.38 min).

[0066] Example 16

[0067] The procedure and conditions were the same as in Example 15, except that CuCl in Example 15 was replaced equimolarly with hydrated Cu(OAc). 2 , and the rest was the same as in Example 15, to obtain 58 mg of the product N-methyl-N-(1-phenylprop-2-yn-1-yl)aniline with a yield of 88% and an enantioselectivity of 92% ee.

[0068] Example 17

[0069] The procedure and conditions were the same as in Example 15, except that CuCl in Example 15 was replaced equimolarly with Cu(CH 3 CN) 4 BF 4 , and the rest was the same as in Example 15, to obtain 59 mg of the product N-methyl-N-(1-phenylprop-2-yn-1-yl)aniline with a yield of 89% and an enantioselectivity of 94% ee.

[0070] Example 18

[0071] The procedure and conditions were the same as in Example 15, except that (R,S)-Ia in Example 15 was replaced equimolarly with (R,S)-Ib, and the rest was the same as in Example 15, to obtain 51 mg of the product N-methyl-N-(1-phenylprop-2-yn-1-yl)aniline with a yield of 77% and an enantioselectivity of 87% ee.

[0072] Example 19

[0073]

[0074] The process and conditions were the same as those in Example 15, except that N-methylaniline in Example 15 was replaced equimolarly with aniline, and the rest was the same as in Example 15. 57 mg of the product N-(1-phenylprop-2-yn-1-yl)aniline (a known compound) was obtained, with a yield of 92%. The enantioselectivity analyzed by chiral HPLC was 90% ee (HPLC conditions: chiralpak AD-H, 40 °C, 254 nm, n-hexane / 2-propanol = 95 / 5, flow rate = 0.8 mL / min, minor enantiomer: t1 = 12.97 min; major enantiomer: t2 = 15.15 min.).

[0075] Example 20

[0076]

[0077] The process and conditions were the same as those in Example 15, except that N-methylaniline in Example 15 was replaced equimolarly with morpholine, and the rest was the same as in Example 15. 58 mg of the product N-(1-phenylprop-2-yn-1-yl)morpholine (a known compound) was obtained, with a yield of 96%. The enantioselectivity analyzed by chiral HPLC was 87% ee (HPLC conditions: chiralcel OJ-H, 40 °C, 254 nm, n-hexane / 2-propanol = 95 / 5, flow rate = 0.8 mL / min, major enantiomer: t1 = 14.25 min; minor enantiomer: t2 = 8.99 min.).

[0078] Example 21

[0079]

[0080] The procedure and conditions were the same as in Example 15, except that 1-phenyl-2-propynyl acetate in Example 15 was replaced equimolarly with 1-(2-naphthyl)-2-propynyl acetate (a known compound), and the rest was the same as in Example 15. The product N-(1-(2-naphthyl)prop-2-yn-1-yl)aniline (a known compound) was obtained in an amount of 77 mg with a yield of 95%, and the enantioselectivity by chiral HPLC analysis was 94% ee (HPLC conditions: chiralcel OD-H, 40 °C, 254 nm, n-hexane / 2-propanol = 95 / 5, flow rate = 0.8 mL / min, major enantiomer: t1 = 7.56 min; minor enantiomer: t2 = 9.62 min.).

[0081] Example 22

[0082]

[0083] The procedure and conditions were the same as in Example 15, except that 1-phenyl-2-propynyl acetate in Example 15 was replaced equimolarly with 1-(2-furyl)-2-propynyl acetate (a known compound), and the rest was the same as in Example 15. The product N-(1-(2-furyl)prop-2-yn-1-yl)aniline (a known compound) was obtained in an amount of 60 mg with a yield of 95%, and the enantioselectivity by chiral HPLC analysis was 94% ee (HPLC conditions: chiralcel AD-H, 40 °C, 254 nm, n-hexane / 2-propanol = 95 / 5, flow rate = 0.8 mL / min, major enantiomer: t1 = 6.08 min; minor enantiomer: t2 = 6.52 min.).

Claims

1. A chiral tridentate P,N,N-ligand, characterized in that: It is a chiral tridentate P,N,N-ligand based on a cis-cyclic 1,2-amino-phosphine skeleton, having a (R,S)-I or (S,R)-II structure as shown below: Among them, (R,S)-I and (S,R)-II are enantiomers of each other; R is hydrogen, C1-C6 straight or branched alkane, C3-C6 cycloalkane, C6-C 10 One or more of aryl or substituted aryl groups; the substituents on the substituted aryl groups are selected from one or more of C1-C6 alkyl, C1-C6 alkoxy, halogen, nitro, ester or cyano; R is preferably one or more of hydrogen, methyl or phenyl.

2. The chiral tridentate P,N,N-ligand according to claim 1, characterized in that: Its advantageous ligand structure is as follows:

3. A method for preparing the chiral tridentate P,N,N-ligand according to claim 1, characterized in that: The preparation route is as follows: R is the same as R in claim 1.

4. The preparation method according to claim 3, characterized in that: The preparation route comprises the following specific steps: Under nitrogen protection, cis-chiral 2-(diphenylphosphine)-1,2,3,4-tetrahydro-1-naphthylamine (R,S)-III and / or (S,R)-IV and 2-pyridine carbonyl compound V are placed in a reaction bottle, a solvent is added, and a dehydrating agent is added under stirring; the reaction solution is heated to reflux, and TCL detection shows that the reaction raw materials are completely consumed. The reaction solution is concentrated under reduced pressure, separated by silica gel column chromatography, concentrated under reduced pressure, and dried in vacuo to obtain a chiral tridentate P,N,N-ligand.

5. The method according to claim 4, characterized in that The solvent is selected from one or more of methanol, ethanol, tetrahydrofuran, ether, ethyl acetate, toluene, xylene, dichloromethane, dichloroethane, etc.; preferably toluene.

6. The method according to claim 4, characterized in that The dehydrating agent is selected from one or more of anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous calcium chloride, silica gel, activated alumina, tetraisopropoxy titanium, etc.; preferably, it is a 1:1 mixture of anhydrous magnesium sulfate and activated alumina.

7. The method according to claim 4, characterized in that The molar ratio of (R,S)-III and / or (S,R)-IV to the 2-pyridinecarbonyl compound V is 1:0.5-2.5; preferably 1:1.0-1.5; more preferably 1:1.1-1.

2.

8. The method according to claim 4, characterized in that The weight ratio of (R,S)-III and / or (S,R)-IV to the dehydrating agent is 1:1-10; preferably 1:5-6.

9. A use of the chiral tridentate P,N,N-ligand according to claim 1, characterized in that: The catalyst composed of the chiral tridentate P, N, N-ligand and the copper metal precursor can be used in the asymmetric catalytic propargyl conversion reaction.

10. The use of the chiral tridentate P,N,N-ligand according to claim 9, characterized in that: The catalyst composed of the chiral tridentate P, N, N-ligand and the copper metal precursor has excellent catalytic activity and stereoselectivity in the asymmetric catalytic propargyl conversion reaction; The molar ratio of the copper metal precursor to the chiral tridentate P,N,N-ligand is 1:0.5-2.5, preferably 1:1.0-1.2.

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