A novel PNNO and PNNN chiral tetradentate ligand and its application in asymmetric hydrogenation

Abstract

The present invention belongs to the field of fine chemicals and discloses a novel PNNO and PNNN chiral tetradentate ligand and its application in asymmetric hydrogenation. The synthesis of this type of ligand can start from cheap and easily available raw materials, with simple steps, being relatively stable in an air atmosphere, having a flexible structure, and strong adjustability of steric hindrance and electronic properties. In particular, the catalyst formed by this type of novel PNNO and PNNN chiral tetradentate ligand and a metal has excellent catalytic activity and stereoselectivity in the application of asymmetric hydrogenation reactions, showing great application potential and broad prospects for industrial production, and having extremely high commercial value.

Description

Technical Field

[0001] The present invention relates to a novel PNNO and PNNN chiral tetradentate ligand and its application in asymmetric hydrogenation, belonging to the field of fine chemical industry. Background Art

[0002] Metal and ligand reagents are used in modern organic synthesis reactions. They can not only construct many new chemical bonds that are difficult to achieve by traditional chemical reactions, promote the efficient progress of reactions, but also reduce production costs and shorten reaction times, providing technical support for the industrial preparation of drugs, materials, and fine chemicals. Metal-catalyzed asymmetric catalytic reactions are the most economical and efficient methods for synthesizing chiral compounds. A large amount of chiral products can be obtained by using a catalytic amount of chiral catalysts. Among them, asymmetric hydrogenation reactions have attracted great attention from chemists due to their unique high atom economy, high enantioselectivity, and environmental friendliness. Asymmetric hydrogenation reactions have made great progress and achieved industrial production, such as the synthesis of L-dopa by Monsanto, the synthesis of L-menthol by Takasago, the synthesis of (S)-alachlor by Novartis. Especially in 2012, BASF successfully realized the synthesis of ten thousand tons of L-menthol by using asymmetric hydrogenation reactions.

[0003] Ligands can improve the reaction efficiency in synthesis reactions, regulate the chemical, regioselective, and stereoselective properties of reactions, and provide favorable support for constructing various new bonds and synthesizing optically pure chemicals. Since ligands are different from general fine chemicals, most of them have relatively complex structures. Especially the preparation of some air-sensitive and chiral phosphine ligands with complex structures has a certain technical threshold. It has become particularly important to develop high-end ligands with independent intellectual property rights, which can significantly reduce the costs of developing new products and new processes relying on ligands and accelerate the development of chemistry and chemical engineering.

[0004] Currently, widely used privileged skeleton ligands include axially chiral BINAP ligands, planar chiral Josiphos ligands, BPE, Duphos, Segphos, spiro skeleton SDP, SKP and other series of ligands. Since the discovery of the Noyori ruthenium-bisphosphine-diamine system and the in-depth study of the bifunctionalization mechanism of metal-ligand cooperative catalysis, ligands containing N-H groups have been widely studied and used in the asymmetric catalytic hydrogenation of ketones. In 1998, the Zhang Xumu group designed and synthesized a class of tridentate ligands (ph-ambox) containing bisoxazoline rings and N-H functional groups, and successfully applied them to the highly stereoselective asymmetric transfer hydrogenation reaction of aromatic ketones [J. Am. Chem. Soc. 1998, 120, 3817.], and synthesized indan-ambox with larger steric hindrance, which was successfully used in the asymmetric hydrogenation reaction of simple ketones [Chem. Commun. 2010, 46, 3979.]. In 2011, the group of Professor Zhou Qilin designed and synthesized tridentate Spiro-PAP ligands. The iridium complex of this ligand is more stable in catalytic hydrogenation and can efficiently and highly selectively reduce simple aryl ketones, achieving the highest turnover number (4550000 TON) so far [Angew. Chem. Int. Ed. 2011, 50, 7329.].

[0005] In 2016, the Zhang Xumu group designed and synthesized a class of novel ferrocenyl chiral tridentate PNN ligands (f-amphox) based on the Ambox ligand. This ligand showed ultra-high activity and stereoselectivity in the asymmetric hydrogenation of aromatic ketones [Org. Lett. 2016, 18, 2938.]. Subsequently, a series of novel ferrocenyl chiral ligands such as f-amphox, f-ampha, f-amphamide, etc. were developed, all of which showed excellent activity and stereoselectivity in the asymmetric hydrogenation of aromatic ketones, greatly enriching the variety of the ligand library.

[0006] A series of novel ferrocenyl chiral tridentate ligands are as follows:

[0007]

[0008] Although many chiral ligands with different chiral centers and backbone structures have been developed so far, which have greatly promoted the development of the asymmetric field, there are still problems such as many synthesis steps, high costs, and limited applications, seriously restricting their industrial production and applications. Moreover, in reality, the substrates are diverse, and there is still an urgent need to develop different ligands to adapt to different substrates. The present invention proposes a new type of multidentate chiral ligand with cheap and easily available raw materials, a concise synthesis route, simple process, easy for large-scale preparation, and convenient for adjusting the structure and electric property. This ligand exhibits ultra-high activity and stereoselectivity in asymmetric hydrogenation reactions. This type of new ligand has broad industrial application prospects and is of great significance for realizing the application value of metal and ligand reagents in industrial production and industrial upgrading. SUMMARY OF THE INVENTION

[0009] The present invention discloses a new type of PNNO and PNNN chiral tetradentate ligands and their applications in asymmetric hydrogenation. The ligands are easy to synthesize, the raw materials are easily available, they are relatively stable in an air atmosphere, have high catalytic activity and high stereoselectivity, and are easy to realize industrial production.

[0010] The present invention is achieved through the following technical solutions. First, the present invention provides a new type of chiral tetradentate ligand, and the ligand is selected from PNNO and PNNN chiral tetradentate ligands, and the general structural formulas are respectively as follows (I) and (II):

[0011]

[0012] In general formulas (I) and (II): R 1 and R 2 are each independently an alkyl group or an aryl group; R 3 and R 4 are independently an alkyl group, an aryl group or a hydrogen atom; R 5 and R 6 are each independently an alkyl group or an aryl group, R 5 and R 6 form a ring or do not form a ring, R 7 is an amino protecting group, selected from benzyloxycarbonyl (Cbz), tert-butoxycarbonyl (Boc), fluorenylmethoxycarbonyl (Fmoc), allyloxycarbonyl (Alloc), trimethylsilylethoxycarbonyl (Teoc), methoxy (or ethoxy) carbonyl, phthaloyl (Pht), p-toluenesulfonyl (Ts), trifluoroacetyl (Tfa), nitrobenzenesulfonyl (Ns), pivaloyl, benzoyl, triphenylmethyl (Trt), 2,4-dimethoxybenzyl (Dmb), p-methoxybenzyl (PMB), benzyl (Bn), etc.

[0013] As a preferred embodiment of the present invention, the alkyl group is selected from C1-6 alkyl groups, and the C1-6 alkyl groups are selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, 1-ethylpropyl, 2-methylbutyl, tert-pentyl, 1,2-dimethylpropyl, isopentyl, neopentyl, n-hexyl, isohexyl, sec-hexyl, tert-hexyl, neohexyl, 2-methylpentyl, 1,2-dimethylbutyl, 1-ethylbutyl; the aryl group is selected from phenyl.

[0014] As a preferred embodiment of the present invention, the multidentate chiral ligand is L1-L8, and each structure contains two enantiomers. The specific structures are as follows:

[0015]

[0016] More preferably L3 or L5.

[0017] The present invention further provides a method for the PNNO tetradentate ligand, and the synthesis route is as follows:

[0018]

[0019] The present invention further provides a method for the PNNN tetradentate ligand, and the synthesis route is as follows:

[0020]

[0021] Furthermore, it can be achieved through the following technical solutions, including the following steps:

[0022] 1) N-Boc glycine (S1) undergoes a condensation reaction with a chiral amino acid (S2 or S2'), or a chiral diamine (S6) under certain conditions to obtain an amide intermediate (S3 or S3'), or S7, and then the amino Boc protection is removed to obtain an ammonia compound (S4 or S5), or S8. The deprotection reagent is trifluoroacetic acid, methanesulfonic acid, hydrochloric acid, sulfuric acid, phosphoric acid, etc., preferably trifluoroacetic acid and hydrochloric acid;

[0023] 2) Starting from Ugi's amine (1), it is deprotonated by butyllithium and phosphine is added to obtain an intermediate chiral aminophosphine (2), and then the dimethylamino group is replaced by acetoxy to obtain an intermediate acetate (3);

[0024] 3) The acetate (3) reacts with the corresponding ammonia compound (S4 or S5), or S8 in the presence of triethylamine to obtain the corresponding chiral ligand.

[0025] The present invention further provides a series of catalysts, that is, a complex formed by the obtained novel chiral multidentate ligand and a transition metal, wherein the transition metal is selected from Ru, Rh, Ir, Fe, Co, Ni, Mn, Cu, etc.

[0026] Among them, suitable transition metal precursors include [Ir(NBD)Cl] 2 ; [Ir(NBD) 2 X; [Ir(COD)Cl] 2 ; [Ir(COD) 2 X; [Rh(NBD) 2 X; [Rh(NBD)Cl] 2 ; Rh(acac)(CO) 2 ; [Rh(COD)Cl] 2 ; Rh(ethylene) 2 (acac); [Rh(ethylene) 2 Cl] 2 ; [Rh(COD) 2 X; RhCl(PPh 3 ) 3 ; Ru(arylgroup)X 2 ; RuX 2 (L) 2 (diphosphine); Ru(arene)X 2 (diphosphine); Ru(methallyl) 2 (diphosphine); Ru(arylgroup)X 2 (PPh 3 ); RuX 2 (cymene); RuCl 2 (COD); (Ru(COD) 2 )X; RuX 2 (diphosphine); Ru(ArH)Cl 2 ; Ru(COD)(methallyl) 2 ; (Ni(allyl)X) 2 ; Ni(acac) 2 ; Ni(COD) 2 ; NiX 2 ; MnX 2 ; Mn(acac) 2 ; CoX 2 ; FeX 2 ; CuX; CuX 2 ;

[0027] Among the above transition metal precursors, R represents an alkyl group, an alkoxy group or a substituted alkyl group, aryl is an aryl group, and X is a negative anion, such as Cl - , Br - , I- , BF 4 - , ClO 4 - , SbF 6 - , PF 6 - , TfO - , RCOO - , B(Ar) 4 - , wherein Ar can be 3,5-bis(trifluoromethyl)benzene or fluorobenzene, and L is a solvent molecule such as CH 3 CN, DMF, etc.

[0028] The present invention further provides the use of the catalyst as a catalyst in an asymmetric hydrogenation reaction.

[0029] The catalysts obtained above exhibit excellent activity and stereoselectivity in the asymmetric hydrogenation of ketones. Specifically, a metal precursor and a polydentate ligand of the present invention are complexed in a suitable solvent for a certain period of time to obtain several catalysts for catalytic asymmetric hydrogenation. Then, the complex is mixed with a substrate ketone and added to the corresponding solvent, and a catalytic amount of base is added to activate the catalyst. The reaction solution is transferred to a stainless steel autoclave, purged with hydrogen three times, filled with hydrogen at a certain pressure, and reacted at room temperature or heated for several hours. After carefully and slowly releasing the gas, the reaction solution is filtered through a thin layer of silica gel and then dried by evaporation to obtain the chiral product alcohol.

[0030] As a preferred technical solution of the present invention, the solvent in the asymmetric hydrogenation reaction is preferably one or a mixture in any proportion of isopropanol, ethanol, toluene, and n-hexane, more preferably a mixture of isopropanol, toluene, or any proportion thereof; the base is one or a mixture in any proportion of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, potassium hydroxide, sodium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, and cesium carbonate, more preferably a mixture of potassium tert-butoxide, potassium hydroxide, sodium hydroxide, and potassium carbonate.

[0031] As a preferred technical solution of the present invention, the pressure of hydrogen is preferably 10 - 80 atm, more preferably 20 - 50 atm; the reaction temperature is preferably 20 - 80 °C, more preferably 20 - 50 °C.

[0032] The present invention further provides an intermediate compound, and the structure of the compound is as follows formula S8-1 (including two stereoisomers):

[0033]

[0034] The present invention further provides an intermediate compound, and the structure of the compound is as follows formula S8-2 (including two stereoisomers):

[0035]

[0036] The present invention has the following beneficial effects compared with the prior art:

[0037] 1) The present invention has successfully developed a kind of chiral PNNO and PNNN tetradentate ligands and their synthesis methods. Such ligands are flexible and variable, with strong adjustability of spatial configuration and electric property, and strong substrate universality. Their synthesis can start from cheap and easily available raw materials, with simple steps, easy to scale up, and suitable for industrial application.

[0038] 2) The complexes formed by such chiral PNNO and PNNN tetradentate ligands and metal iridium have very high reaction activity and stereoselectivity in the asymmetric hydrogenation reaction of ketones.

[0039] 3) The present invention has the advantages of simple operation, good stability, wide universality, low cost, environmental friendliness, etc., with good industrialization prospects, capable of bringing huge economic benefits, and having extremely high commercial value. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 , 1H NMR spectrum of ligand L2 of the present invention;

[0041] Figure 2 , 13C NMR spectrum of ligand L2 of the present invention;

[0042] Figure 3 , 1H NMR spectrum of ligand L3 of the present invention;

[0043] Figure 4 , 13C NMR spectrum of ligand L3 of the present invention;

[0044] Figure 5 , 1H NMR spectrum of ligand L6 of the present invention;

[0045] Figure 6 , 13C NMR spectrum of ligand L6 of the present invention;

[0046] Figure 7 , 1H NMR spectrum of ligand L7 of the present invention;

[0047] Figure 8 , 13C NMR spectrum of ligand L7 of the present invention;

[0048] Figure 9 , 1H NMR spectrum of ligand L8 of the present invention;

[0049] Figure 10 , 13C NMR spectrum of ligand L8 of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0050] The present application will be further described in detail below in conjunction with embodiments and the accompanying drawings, but the implementation manners of the present application are not limited thereto.

[0051] Synthesis of Intermediate (SC,RP)-2 in Example 1

[0052]

[0053] Under nitrogen protection, 60 mL of a n-BuLi hexane solution (2.5 mol / L, 1.2 equiv.) was added dropwise to a solution of 30 g of (S)-1 (1.0 equiv.) in methyl tert-butyl ether (250 mL) at 0 °C. After the addition was complete, the mixture was allowed to warm to room temperature and stirred for 4.0 h. Subsequently, Ar 2 PCl (1.2 equivalents) was added dropwise to the reaction solution under reflux, and the reflux was continued for about 4 h. The reaction was monitored by TLC. After the reaction was completed, the reaction was quenched with water, and the organic phase was extracted with methyl tert-butyl ether. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to obtain a red oily liquid. A certain amount of methyl tert-butyl ether was added for slurrying to obtain an orange-yellow solid product (S C ,R P )-2 (yield 65%-85%).

[0054] Synthesis of Intermediate (S C ,R P )-3 in Example 2

[0055]

[0056] Under nitrogen protection, a mixture of (S C ,R P )-2 (30 mmol) and acetic anhydride (24 mL) was heated at 100 °C for 1-4 h. The reaction was monitored by TLC. After the reaction was completed, acetic anhydride was removed by rotary evaporation under reduced pressure to obtain an orange-yellow solid with a yield > 95%, which was used directly in the next step without purification.

[0057] Synthesis of Intermediate S4 in Example 3

[0058]

[0059] N-Boc glycine (S1) (1.2 equiv.) and chiral amino acid (S2) (1.0 equiv.) were dissolved in dichloromethane, and a condensation reaction occurred under the action of a condensing agent DCC (1.5 equiv.). After the reaction was monitored by TLC and completed, the solid by-products were filtered off to obtain the crude amide intermediate (S3), which was purified by column chromatography to obtain the pure product S3 with a yield of 72%-90%.

[0060] Compound S3 was dissolved in trifluoroacetic acid / dichloromethane (V:V = 1:1), and the reaction was carried out at room temperature for 4 hours. The reaction was monitored by TLC until completion. The solvent and excess trifluoroacetic acid were evaporated, and the residue was neutralized with saturated sodium bicarbonate solution. The crude product was extracted with dichloromethane (3 times), the organic phases were combined, dried over anhydrous sodium sulfate, filtered to obtain S4, and the crude product yield was >90%. It was directly used for the next step without purification.

[0061] Synthesis of Intermediate S5 in Example 4

[0062]

[0063] N-Boc glycine (S1) (1.2 equiv) and proline (S2’) (1.0 equiv) were dissolved in dichloromethane, and a condensation reaction occurred under the action of a condensing agent DCC (1.5 equiv). After the reaction was monitored by TLC until completion, the solid by-products were filtered to obtain the crude amide intermediate (S3’), and the pure product S3’ was obtained by column chromatography separation and purification with a yield of 75%.

[0064] Compound S3’ was dissolved in trifluoroacetic acid / dichloromethane (V:V = 1:1), and the reaction was carried out at room temperature until the reaction was monitored by TLC until completion. The solvent and excess trifluoroacetic acid were evaporated, and the residue was neutralized with saturated sodium bicarbonate solution. The crude product was extracted with dichloromethane (3 times), the organic phases were combined, dried over anhydrous sodium sulfate, filtered to obtain S5, and the crude product yield was 93%. It was directly used for the next step without purification.

[0065] Synthesis of Intermediate S8 in Example 5

[0066]

[0067] N-Boc glycine (S1) (1.2 equiv) and diamine compound (S6) (1.0 equiv) were dissolved in dichloromethane, and a condensation reaction occurred under the action of a condensing agent DCC (1.5 equiv). After the reaction was monitored by TLC until completion, the solid by-products were filtered to obtain the crude amide intermediate (S7), and the pure product S7 was obtained by column chromatography separation and purification with a yield of 60 - 80%.

[0068] Compound S7 was dissolved in trifluoroacetic acid / dichloromethane (V:V = 1:1), and the reaction was carried out at room temperature until the reaction was monitored by TLC until completion. The solvent and excess trifluoroacetic acid were evaporated, and the residue was neutralized with saturated sodium bicarbonate solution. The crude product was extracted with dichloromethane (3 times), the organic phases were combined, dried over anhydrous sodium sulfate, filtered to obtain S8, and the crude product yield was 80 - 95%. It was directly used for the next step without purification.

[0069]

[0070] (R,R)-S8-1: 11H NMR (600 MHz, Chloroform-d) δ 8.34 (s, 1H), 7.71 (d, J = 7.9 Hz, 2H), 7.45 (d, J = 8.7 Hz, 1H), 7.24 (d, J = 7.9 Hz, 2H), 3.67 (td, J = 10.9, 4.2 Hz, 1H), 3.53 (s, 2H), 2.91 (td, J = 10.9, 4.2 Hz, 1H), 2.39 (s, 3H), 2.01 - 1.51 (m, 4H), 1.44 - 0.97 (m, 4H). 13 13C NMR (151 MHz, CDCl 3 ) δ 170.68, 143.02, 138.61, 129.54, 126.79, 58.33, 52.63, 42.89, 32.84, 31.85, 24.64, 24.33, 21.42.

[0071]

[0072] (S,S)-S8-2: 1 1H NMR (600 MHz, Chloroform-d) δ 8.34 (s, 1H), 7.41 (d, J = 8.2 Hz, 2H), 7.17 - 7.10 (m, 3H), 7.04 (m, 2H), 6.97 (m, 3H), 6.92 (t, J = 7.5 Hz, 2H), 6.86 (d, J = 7.1 Hz, 2H), 5.26 (dd, J = 10.2, 8.2 Hz, 1H), 4.65 (d, J = 10.3 Hz, 1H), 3.52 (d, 2H), 2.26 (s, 3H). 13 13C NMR (151 MHz, CDCl 3 ) δ 173.02, 142.55, 138.20, 138.11, 137.81, 129.06, 128.47, 127.96, 127.79, 127.55, 127.54, 127.28, 126.70, 63.73, 58.64, 44.15, 21.33.

[0073] Synthesis of Ligand L1 in Example 6

[0074]

[0075] In a 50 mL reaction tube, 0.91 g (2.0 mmol) of acetate 3a and 0.32 g (2.2 mmol) of S4-1 were added, and N was displaced 2After that, 0.41 g (4 mmol, 2 equiv) of triethylamine and 20 mL of anhydrous methanol were successively added. After stirring at room temperature for 2 h, the reaction was heated under reflux overnight. The mixture was concentrated by rotary evaporation, and column chromatography was performed to obtain a pale yellow foamy solid L1 with a mass of 0.52 g and a yield of 48%.

[0076] 1 H NMR (600 MHz, CDCl 3 ) δ 7.61 - 7.52 (m, 2H), 7.45 - 7.37 (m, 3H), 7.29 - 7.22 (m, 5H), 5.10 (br, 1H), 4.56 (s, 1H), 4.38 (s, 1H), 4.42 - 4.30 (m, 2H), 4.23 - 4.16 (m, 1H), 3.99 - 3.95 (m, 5H), 3.11 (d, J = 16.3 Hz, 1H), 2.85 (d, J = 16.3 Hz, 1H), 1.60 - 1.52 (m, 6H).

[0077] Synthesis of Ligand L2 in Example 7

[0078]

[0079] In a 50 mL reaction tube, 0.91 g (2.0 mmol) of acetate 3a and 0.38 g (2.2 mmol) of S4 - 2 were added. After replacing N 2 After that, 0.41 g (4 mmol, 2 equiv) of triethylamine and 20 mL of anhydrous methanol were successively added. After stirring at room temperature for 2 h, the reaction was heated under reflux overnight. The mixture was concentrated by rotary evaporation, and column chromatography was performed to obtain a pale yellow foamy solid L2 with a mass of 0.58 g and a yield of 51%.

[0080] 1 H NMR (600 MHz, CDCl 3 ) δ 7.60 - 7.54 (m, 2H), 7.41 - 7.36 (m, 3H), 7.30 - 7.21 (m, 6H), 5.62 (br, 1H), 4.58 (s, 1H), 4.41 - 4.34 (m, 1H), 4.39 (s, 1H), 4.20 - 4.14 (m, 1H), 3.98 (brs, 5H), 3.99 - 3.95 (m, 1H), 3.15 (d, J = 15.6 Hz, 1H), 2.76 (d, J = 16.2 Hz, 1H), 2.14 - 2.05 (m, 1H), 1.61 (d, J = 6.6 Hz, 3H), 0.84 (d, J = 6.6 Hz, 3H), 0.81 (d, J = 6.6 Hz, 3H); 13 C NMR (150 MHz, CDCl 3)δ175.2,169.3,139.1(d,J = 8.6Hz),136.8(d,J = 7.8Hz),135.0(d,J = 21.2Hz),132.6(d,J = 18.6Hz),129.4,128.7,128.6(d,J = 6.2Hz),128.3(d,J = 8.1Hz),93.6(d,J = 24.0Hz),75.5(d,J = 9.5Hz),71.9(d,J = 3.6Hz),70.9,70.1(d,J = 3.5Hz),70.1,70.0,69.8,65.9,58.4,51.9(d,J = 9.9Hz),47.0,30.9,19.5,19.4; 31 PNMR(243MHz,CDCl 3 )δ - 26.41(s).

[0081] Among them, Figure 1 , the 1H NMR spectrum of ligand L2; Figure 2 , the 13C NMR spectrum of ligand L2.

[0082] Synthesis of Ligand L3 in Example 8

[0083]

[0084] In a 50 mL reaction tube, 0.91 g (2.0 mmol) of acetate 3a and 0.41 g (2.2 mmol) of S4-3 were added. After replacing N 2 , 0.17 mL (1.2 mmol, 3 equiv) of triethylamine and 20 mL of anhydrous methanol were successively added. After stirring at room temperature for 2 h, the reaction was heated under reflux overnight, concentrated by rotary evaporation, and column chromatography was carried out to obtain a pale yellow foamy solid L3 with a mass of 0.59 g and a yield of 47%.

[0085] 1 H NMR(400MHz,CDCl 3 )δ7.62 - 7.52(m,2H),7.42 - 7.36(m,3H),7.30 - 7.19(m,6H),5.40(br),4.55(s,1H),4.41 - 4.32(m,2H),4.14(d,J = 9.1Hz,1H),3.98(brs,5H),3.98 - 3.93(m,1H),3.15(d,J = 15.8Hz,1H),2.69(d,J = 16.0Hz,1H),1.58(d,J = 6.9Hz,3H),0.91(s,9H); 13 C NMR(101MHz,CDCl 3)δ 174.1, 169.6, 139.1 (d, J = 8.8 Hz), 136.9 (d, J = 8.0 Hz), 135.0 (d, J = 21.1 Hz), 132.6 (d, J = 18.2 Hz), 129.4, 128.7, 128.6 (d, J = 6.6 Hz), 128.3 (d, J = 8.1 Hz), 93.8, 77.2, 75.5 (d, J = 9.5 Hz), 71.8 (d, J = 3.9 Hz), 70.1 (d, J = 3.6 Hz), 70.1, 69.9, 60.8, 51.6 (d, J = 10.2 Hz), 46.9, 34.4, 26.8, 19.5; 31 1H NMR (162 MHz, CDCl 3 ) δ -26.47 (s).

[0086] Among them, Figure 3 , the 1H NMR spectrum of ligand L3; Figure 4 , the 13C NMR spectrum of ligand L3.

[0087] Example 9 Synthesis of Ligand L4

[0088]

[0089] In a 50 mL reaction tube, 0.91 g (2.0 mmol) of acetate 3a and 0.46 g (2.2 mmol) of S4-5 were added. After replacing N 2 , 0.41 g (4 mmol, 2 equiv) of triethylamine and 20 mL of anhydrous methanol were successively added. After stirring at room temperature for 2 h, the reaction was heated under reflux overnight, concentrated by rotary evaporation, and column chromatography was used to obtain a pale yellow foamy solid L4 with a mass of 0.56 g and a yield of 46%.

[0090] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.55 - 7.48 (m, 2H), 7.41 - 7.30 (m, 4H), 7.28 - 7.11 (m, 10H), 5.12 (br, 1H), 4.57 (s, 1H), 4.42 - 4.35 (m, 2H), 4.20 - 4.14 (m, 1H), 3.98 (s, 5H), 3.95 - 3.82 (m, 3H), 1.29 (d, J = 6.6 Hz, 3H).

[0091] Example 10 Synthesis of Ligand L5

[0092]

[0093] In a 50 mL reaction tube, 0.97 g (2.0 mmol) of acetate 3b and 0.41 g (2.2 mmol) of S4-3 were added, and N was displaced. 2 After that, 0.41 g (4 mmol, 2 equiv) of triethylamine and 20 mL of anhydrous methanol were successively added. After stirring at room temperature for 2 h, the reaction was heated to reflux overnight. The mixture was concentrated by rotary evaporation, and column chromatography was performed to obtain a pale yellow foamy solid L5 with a mass of 0.51 g and a yield of 43%.

[0094] 1 H NMR (400 MHz, CDCl 3 ) δ 7.55 (d, J = 8.4 Hz, 1H), 7.43 (t, J = 7.9 Hz, 2H), 7.24 (d, J = 7.6 Hz, 2H), 7.15 (t, J = 7.4 Hz, 2H), 7.08 (d, J = 7.5 Hz, 2H), 5.40 (br, 1H), 4.55 (s, 1H), 4.41 - 4.32 (m, 2H), 4.14 (d, J = 9.1 Hz, 1H), 3.98 (brs, 5H), 3.98 - 3.93 (m, 1H), 3.15 (d, J = 15.8 Hz, 1H), 2.69 (d, J = 16.0 Hz, 1H), 1.58 (d, J = 6.9 Hz, 3H), 0.91 (s, 9H).

[0095] Synthesis of Ligand L6 in Example 11

[0096]

[0097] In a 50 mL reaction tube, 0.91 g (2.0 mmol) of acetate 3a and 0.38 g (2.2 mmol) of S5 were added, and N was displaced. 2 After that, 0.41 g (4 mmol, 2 equiv) of triethylamine and 20 mL of anhydrous methanol were successively added. After stirring at room temperature for 2 h, the reaction was heated to reflux overnight. The mixture was concentrated by rotary evaporation, and column chromatography was performed to obtain a pale yellow foamy solid L6 with a mass of 0.48 g and a yield of 42%.

[0098] 1 H NMR (600 MHz, CDCl 3)δ 7.55 - 7.47 (m, 2H), 7.38 - 7.33 (m, 3H), 7.31 - 7.21 (m, 5H), 6.06 - 5.98 (m, 1H), 4.49 (s, 1H), 4.36 (t, 1H), 4.08 (s, 5H), 3.85 (s, 1H), 3.43 (d, J = 16.9 Hz, 1H), 3.40 - 3.33 (m, 1H), 2.91 (d, J = 16.7 Hz, 1H), 2.13 (t, J = 11.3 Hz, 1H), 2.03 - 1.75 (m, 4H), 1.65 - 1.55 (m, 1H), 1.50 (d, J = 6.9 Hz, 3H); 13 C NMR (150 MHz, CDCl 3 )δ 164.7, 163.6, 139.3 (d, J = 11.9 Hz), 136.3 (d, J = 9.9 Hz), 134.8 (d, J = 20.6 Hz), 133.1 (d, J = 20.6 Hz), 129.1, 128.5, 128.3 (d, J = 6.5 Hz), 128.2 (d, J = 7.6 Hz), 91.5 (d, J = 26.0 Hz), 76.7 (d, J = 10.6 Hz), 72.5 (d, J = 5.4 Hz), 70.2 (d, J = 3.2 Hz), 70.1, 69.5, 57.7, 46.9 (d, J = 8.7 Hz), 46.2, 44.8, 28.0, 22.6, 16.5; 31 P NMR (243 MHz, CDCl 3 )δ - 27.57 (s).

[0099] Among them, Figure 5 , the proton NMR spectrum of ligand L6; Figure 6 , the carbon NMR spectrum of ligand L6.

[0100] Example 12 Synthesis of Ligand L7

[0101]

[0102] In a 50 mL reaction tube, 0.91 g (2.0 mmol) of acetate 3a and 0.72 g (2.2 mmol) of S8 - 1 were added. After displacing N 2 , 0.41 g (4 mmol, 2 equiv) of triethylamine and 2 mL of anhydrous methanol were successively added. After stirring at room temperature for 2 h, the reaction was heated under reflux overnight. The mixture was concentrated by rotary evaporation, and column chromatography was performed to obtain a light yellow foamy solid L7 with a mass of 0.63 g and a yield of 40%.

[0103] 1 H NMR (600 MHz, CDCl 3)δ 7.75 - 7.66 (m, 2H), 7.55 (tt, J = 8.8, 3.5 Hz, 2H), 7.43 - 7.34 (m, 3H), 7.25 (dd, J = 5.9, 4.0 Hz, 4H), 7.21 - 7.09 (m, 3H), 5.83 (d, J = 5.5 Hz, 1H), 4.41 (q, J = 1.9 Hz, 1H), 4.32 (t, J = 2.6 Hz, 1H), 4.06 (tt, J = 6.7, 3.3 Hz, 1H), 3.98 (s, 5H), 3.85 (dt, J = 2.4, 1.1 Hz, 1H), 3.50 - 3.42 (m, 1H), 3.00 (tt, J = 10.5, 4.8 Hz, 1H), 2.83 - 2.68 (m, 2H), 2.41 (s, 3H), 2.17 (s, 1H), 2.00 (dd, J = 12.4, 4.3 Hz, 1H), 1.63 - 1.54 (m, 3H), 1.32 (d, J = 6.7 Hz, 2H), 1.30 - 1.23 (m, 2H), 1.22 - 1.10 (m, 2H), 0.99 (m, 1H), 0.86 (m, 1H); 13 13C NMR (151 MHz, CDCl 3 )δ 174.13, 142.52, 140.37, 140.34, 139.33, 137.40, 137.34, 135.05, 134.91, 132.46, 132.34, 129.45, 129.28, 128.42, 128.38, 128.26, 128.24, 128.19, 126.82, 96.81 (d, J = 24.4 Hz), 74.94, 74.88, 71.71, 71.68, 69.73, 69.44, 69.41, 69.25, 59.67, 51.78, 51.74, 51.60, 48.59, 34.16, 31.69, 24.56, 24.24, 21.58, 19.40; 31 31P NMR (243 MHz, CDCl 3 )δ -24.55.

[0104] Among them, Figure 7 , the 1H NMR spectrum of ligand L7; Figure 8 , the 13C NMR spectrum of ligand L7.

[0105] Synthesis of ligand L8 in Example 13

[0106]

[0107] In a 50 mL reaction tube, add 0.91 g (2.0 mmol) of acetate 3a and 0.93 g (2.2 mmol) of S8-2, displace N2 After that, 0.41 g (4 mmol, 2 equiv) of triethylamine and 2 mL of anhydrous methanol were successively added. After stirring at room temperature for 2 h, the reaction was heated under reflux overnight. The mixture was concentrated by rotary evaporation, and column chromatography was performed to obtain 0.62 g of a pale yellow foamy solid L8, with a yield of 38%.

[0108] 1 H NMR (600 MHz, CDCl 3 ) δ 7.89 (d, J = 8.2 Hz, 1H), 7.54 (ddd, J = 9.6, 4.9, 2.8 Hz, 2H), 7.41 - 7.37 (m, 3H), 7.35 (d, J = 8.0 Hz, 2H), 7.30 - 7.21 (m, 5H), 7.18 - 7.08 (m, 3H), 7.01 - 6.95 (m, 1H), 6.95 - 6.88 (m, 4H), 6.87 - 6.84 (m, 2H), 6.80 (d, J = 7.2 Hz, 2H), 6.50 (d, J = 6.5 Hz, 1H), 4.98 (dd, J = 9.9, 8.2 Hz, 1H), 4.57 (dd, J = 10.0, 6.1 Hz, 1H), 4.44 (q, J = 1.9 Hz, 1H), 4.32 (d, J = 2.5 Hz, 1H), 4.14 - 4.08 (m, 2H), 3.96 (s, 5H), 3.82 (dt, J = 2.4, 1.2 Hz, 1H), 2.89 - 2.79 (m, 2H), 2.27 (s, 3H), 1.26 (dd, J = 6.9, 4.7 Hz, 4H); 13 C NMR (151 MHz, CDCl 3 ) δ 174.46, 142.40, 139.98 (d, J = 10.0 Hz), 138.19, 137.99, 137.53, 136.95 (d, J = 8.5 Hz), 134.95, 134.81, 132.63, 132.50, 129.24, 128.96, 128.68, 128.63, 128.59, 128.55, 128.23, 128.18, 127.91, 127.85, 127.60, 127.51, 127.22, 126.76, 96.45, 96.29, 75.25 (d, J = 8.9 Hz), 71.54 (d, J = 4.3 Hz), 69.73, 69.68, 69.25, 64.09, 60.40, 58.70, 51.51 (d, J = 8.3 Hz), 48.32, 21.38, 19.12, 14.22; 31 P NMR (243 MHz, CDCl 3 ) δ -24.67.

[0109] Among them, Figure 9 , the 1H NMR spectrum of ligand L8; Figure 10 , the 13C NMR spectrum of ligand L8.

[0110] Asymmetric Catalytic Hydrogenation of Acetophenone in Examples 14 - 21 (S / C = 10,000)

[0111]

[0112] Under the protection of argon in a glove box, the metal precursor [Ir(COD)Cl] 2 (1.4 mg, 2.0×10 -3 mmol) and different ligands L1 - L8 (4.2×10 -3 mmol) were separately added to a 4.0 mL reaction flask, 2 mL of the solvent i PrOH was added for dissolution, and the mixture was stirred for 2 h. The complexed catalyst solution was kept for use. In a 5.0 mL hydrogenation flask, sodium tert - butoxide (0.002 mmol) and freshly distilled acetophenone (0.2 mmol) were added. Then, 1.0 mL i PrOH was added for dissolution. The freshly prepared catalyst solution (10 μL) was added dropwise into the reaction system through a microsyringe. After putting it into the autoclave and sealing it, it was taken out of the glove box. The autoclave body was rinsed three times with 10 atm of H 2 , and then filled with 20 atm of H 2 and the inlet valve was closed tightly. The reaction was stirred at room temperature for 24 h. After the reaction was completed, the deflation valve was opened in the fume hood, and the hydrogen in the autoclave body was slowly released. The reaction solution in the hydrogenation flask was directly subjected to rapid silica gel column chromatography using ethyl acetate as the eluent to remove the metal complex. The solvent was evaporated to dryness to obtain the chiral alcohol product. The ee value of the product was determined by chiral high - performance liquid chromatography and chiral gas chromatography, and the optical rotation value of the product was measured. The results are shown in Table 1.

[0113] Table 1 Ligand Screening for Asymmetric Catalytic Hydrogenation of Acetophenone

[0114]

[0115]

[0116] Optimization of Reaction Conditions for Asymmetric Catalytic Hydrogenation of Acetophenone in Examples 22 - 36

[0117] Using L3 as the ligand, according to the above - mentioned operation method, the reaction conditions for this hydrogenation reaction were optimized. The results are shown in Table 2:

[0118] Table 2 Optimization of Reaction Conditions for Asymmetric Catalytic Hydrogenation of Acetophenone

[0119] Number Ligand Reaction Solvent Base conv.(%) ee(%) Example 16 L3 <![CDATA i PrOH]]> <![CDATA t BuONa]]> >99 >99 Example 22 L3 MeOH <![CDATA t BuONa]]> 0 - Example 23 L3 EtOH <![CDATA t BuONa]]> 65 93 Example 24 L3 Hexane <![CDATA t BuONa]]> 94 >99 Example 25 L3 Toluene <![CDATA t BuONa]]> >99 >99 Example 26 L3 THF <![CDATA t BuONa]]> 90 97 Example 27 L3 DCM <![CDATA t BuONa]]> 98 99 Example 28 L3 EtOAc <![CDATA t BuONa]]> 12 91 Example 29 L3 <![CDATA i PrOH]]> <![CDATA t BuOK]]> >99 >99 Example 30 L3 <![CDATA i PrOH]]> NaOMe 99 >99 Example 31 L3 <![CDATA i PrOH]]> KOMe >99 >99 Example 32 L3 <![CDATA i PrOH]]> <![CDATA[Sodium 2 Carbon monoxide 3 > >99 >99 Example 33 L3 <![CDATA i PrOH]]> <![CDATA[K 2 CO 3 > >99 >99 Example 34 L3 <![CDATA i PrOH]]> NaOH >99 >99 Example 35 L3 <![CDATA i PrOH]]> KOH >99 >99 Example 36 L3 <![CDATA i PrOH]]> <![CDATA t BuOLi]]> >99 97

[0120] Example 37 Asymmetric Catalytic Hydrogenation of p-Methylacetophenone (S / C = 10,000)

[0121]

[0122] In a glove box under argon protection, the metal precursor [Ir(COD)Cl] 2 (1.4 mg, 2.0×10 -3 mmol) and ligand L3 (4.2×10 -3 mmol) were added to a 4.0 mL reaction flask, and 2 mL of the solvent i PrOH was added for dissolution, and the mixture was stirred for 2 h. The complexed catalyst solution was ready for use. In a 5.0 mL hydrogenation flask, sodium tert-butoxide (0.002 mmol) and freshly distilled p-methylacetophenone (0.2 mmol) were added, and then 1.0 mL i PrOH was added for dissolution. The freshly prepared catalyst solution (10 μL) was added dropwise to the reaction system through a microsyringe. After placing it in the autoclave and sealing it, it was removed from the glove box. The autoclave body was rinsed three times with 10 atm of H 2 , and then filled with 20 atm of H 2 , and the intake valve was closed tightly. The reaction was stirred at room temperature for 24 h. After the reaction was completed, the deflation valve was opened in the fume hood, and the hydrogen in the autoclave body was slowly released. The reaction solution in the hydrogenation flask was directly subjected to rapid silica gel column chromatography using ethyl acetate as an eluent to remove the metal complex. The solvent was evaporated to dryness to obtain the product p-methylphenethyl alcohol. By high performance liquid chromatography analysis, the ee value of the product was >99%.

[0123] Example 38 Asymmetric Catalytic Hydrogenation of p-Methoxyacetophenone (S / C = 10,000)

[0124]

[0125] In a 5.0 mL hydrogenation flask, sodium tert-butoxide (0.002 mmol) and freshly distilled p-methoxyacetophenone (0.2 mmol) were added, and then 1.0 mL i PrOH was added for dissolution. The freshly prepared catalyst solution (10 μL) from Example 37 was added dropwise to the reaction system through a microsyringe. After placing it in the autoclave and sealing it, it was removed from the glove box. The autoclave body was rinsed three times with 10 atm of H 2 , and then filled with 20 atm of H 2Close the inlet valve tightly and stir the reaction at room temperature for 24 h. After the reaction is completed, open the deflation valve in the fume hood and slowly release the hydrogen in the autoclave. Use ethyl acetate as the eluent to directly perform rapid silica gel column chromatography on the reaction solution in the hydrogenation bottle to remove the metal complex. Rotavaporize the solvent to obtain the product p-methoxyphenethyl alcohol. Analyzed by high performance liquid chromatography, the ee value of the product > 99%.

[0126] Example 39 Asymmetric Catalytic Hydrogenation of p-Fluoroacetophenone (S / C = 10,000)

[0127]

[0128] Add sodium tert-butoxide (0.002 mmol) and freshly distilled p-fluoroacetophenone (0.2 mmol) into a 5.0 mL hydrogenation bottle, then add 1.0 mL i PrOH for dissolution. Add the freshly prepared catalyst solution (10 μL) from Example 37 above dropwise into the reaction system through a microsyringe. Put it into the autoclave, seal it, take it out of the glove box, and flush the autoclave three times with H 2 at 10 atmospheres. Then fill the autoclave with 20 atm H 2 Close the inlet valve tightly and stir the reaction at room temperature for 24 h. After the reaction is completed, open the deflation valve in the fume hood and slowly release the hydrogen in the autoclave. Use ethyl acetate as the eluent to directly perform rapid silica gel column chromatography on the reaction solution in the hydrogenation bottle to remove the metal complex. Rotavaporize the solvent to obtain the product p-fluorophenethyl alcohol. Analyzed by high performance liquid chromatography, the ee value of the product > 99%.

[0129] Example 40 Asymmetric Catalytic Hydrogenation of p-Chloroacetophenone (S / C = 10,000)

[0130]

[0131] Add sodium tert-butoxide (0.002 mmol) and freshly distilled p-chloroacetophenone (0.2 mmol) into a 5.0 mL hydrogenation bottle, then add 1.0 mL i PrOH for dissolution. Add the freshly prepared catalyst solution (10 μL) from Example 37 above dropwise into the reaction system through a microsyringe. Put it into the autoclave, seal it, take it out of the glove box, and flush the autoclave three times with H 2 at 10 atmospheres. Then fill the autoclave with 20 atm H 2 Close the inlet valve tightly and stir the reaction at room temperature for 24 h. After the reaction is completed, open the deflation valve in the fume hood and slowly release the hydrogen in the autoclave. Use ethyl acetate as the eluent to directly perform rapid silica gel column chromatography on the reaction solution in the hydrogenation bottle to remove the metal complex. Rotavaporize the solvent to obtain the product p-chlorophenethyl alcohol. Analyzed by high performance liquid chromatography, the ee value of the product > 99%.

[0132] Example 41 Asymmetric catalytic hydrogenation of m-chloroacetophenone (S / C = 10,000)

[0133]

[0134] Sodium tert-butoxide (0.002 mmol) and freshly distilled m-chloroacetophenone (0.2 mmol) were added to a 5.0 mL hydrogenation flask, and then 1.0 mL i PrOH was added for dissolution. The freshly prepared catalyst solution (10 μL) from Example 37 above was added dropwise to the reaction system through a microsyringe. After placing it in an autoclave and sealing it, it was removed from the glove box. The autoclave body was rinsed three times with 10 atm of H 2 and then filled with 20 atm of H 2 and the inlet valve was closed tightly. The reaction was stirred at room temperature for 24 h. After the reaction was completed, the deflation valve was opened in the fume hood, and the hydrogen in the autoclave body was slowly released. The reaction solution in the hydrogenation flask was directly subjected to rapid silica gel column chromatography using ethyl acetate as an eluent to remove the metal complex. The solvent was evaporated to dryness to obtain the product m-chlorophenethyl alcohol. By high performance liquid chromatography analysis, the ee value of the product was >99%.

[0135] Example 42 Asymmetric catalytic hydrogenation of o-chloroacetophenone (S / C = 10,000)

[0136]

[0137] Sodium tert-butoxide (0.002 mmol) and freshly distilled o-chloroacetophenone (0.2 mmol) were added to a 5.0 mL hydrogenation flask, and then 1.0 mL i PrOH was added for dissolution. The freshly prepared catalyst solution (10 μL) from Example 37 above was added dropwise to the reaction system through a microsyringe. After placing it in an autoclave and sealing it, it was removed from the glove box. The autoclave body was rinsed three times with 10 atm of H 2 and then filled with 20 atm of H 2 and the inlet valve was closed tightly. The reaction was stirred at room temperature for 24 h. After the reaction was completed, the deflation valve was opened in the fume hood, and the hydrogen in the autoclave body was slowly released. The reaction solution in the hydrogenation flask was directly subjected to rapid silica gel column chromatography using ethyl acetate as an eluent to remove the metal complex. The solvent was evaporated to dryness to obtain the product o-chlorophenethyl alcohol. By high performance liquid chromatography analysis, the ee value of the product was >99%.

[0138] Example 43 Asymmetric catalytic hydrogenation of 2-acetonaphthone (S / C = 10,000)

[0139]

[0140] Sodium tert-butoxide (0.002 mmol) and freshly distilled 2-acetylnaphthalene (0.2 mmol) were added to a 5.0 mL hydrogenation flask, and then 1.0 mL i PrOH was added for dissolution. The freshly prepared catalyst solution (10 μL) from Example 37 above was added dropwise to the reaction system using a microsyringe. After placing it in an autoclave and sealing it, it was removed from the glove box. The autoclave body was rinsed three times with H 2 at 10 atmospheres, and then filled with H 2 at 20 atmospheres, and the intake valve was closed tightly. The reaction was stirred at room temperature for 24 h. After the reaction was completed, the deflation valve was opened in the fume hood, and the hydrogen in the autoclave was slowly released. The reaction solution in the hydrogenation flask was directly subjected to rapid silica gel column chromatography using ethyl acetate as an eluent to remove the metal complex. The solvent was evaporated to dryness to obtain the product 2-naphthylethanol. By high performance liquid chromatography analysis, the ee value of the product was >99%.

[0141] Example 44 Asymmetric catalytic hydrogenation of 3-pyridylacetone (S / C = 10,000)

[0142]

[0143] Sodium tert-butoxide (0.002 mmol) and freshly distilled 3-pyridylacetone (0.2 mmol) were added to a 5.0 mL hydrogenation flask, and then 1.0 mL i PrOH was added for dissolution. The freshly prepared catalyst solution (10 μL) from Example 37 above was added dropwise to the reaction system using a microsyringe. After placing it in an autoclave and sealing it, it was removed from the glove box. The autoclave body was rinsed three times with H 2 at 10 atmospheres, and then filled with H 2 at 20 atmospheres, and the intake valve was closed tightly. The reaction was stirred at room temperature for 24 h. After the reaction was completed, the deflation valve was opened in the fume hood, and the hydrogen in the autoclave was slowly released. The reaction solution in the hydrogenation flask was directly subjected to rapid silica gel column chromatography using ethyl acetate as an eluent to remove the metal complex. The solvent was evaporated to dryness to obtain the product 3-pyridylethanol. By high performance liquid chromatography analysis, the ee value of the product was >99%.

[0144] Example 45 Asymmetric catalytic hydrogenation of 2-thienylacetone (S / C = 10,000)

[0145]

[0146] Sodium tert-butoxide (0.002 mmol) and freshly distilled 2-thienylacetone (0.2 mmol) were added to a 5.0 mL hydrogenation flask, and then 1.0 mL iDissolve in PrOH, add the newly prepared catalyst solution (10 μL) in Example 37 above dropwise into the reaction system through a microsyringe. After putting it into the autoclave and sealing it, remove it from the glove box, and rinse the autoclave body three times with H 2 Then charge 20 atm of H into the autoclave body 2 And close the intake valve tightly, and stir the reaction at room temperature for 24 h. After the reaction is completed, open the bleed valve in the fume hood, slowly release the hydrogen in the autoclave body, directly use ethyl acetate as the eluent for the reaction solution in the hydrogenation bottle to perform rapid silica gel column chromatography to remove the metal complex, and rotary evaporate the solvent to obtain the product 2-thienylethanol. Analyzed by high performance liquid chromatography, the ee value of the product > 99%.

[0147] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A chiral tetradentate ligand, characterized in that, the ligand is selected from PNNO and PNNN chiral tetradentate ligands, and the structural general formulas are respectively as follows (I) and (II): ， ， In general formula (I): R 1 is 4-methylphenyl or phenyl, R 2 is 4-methylphenyl or phenyl, and R 1 and R 2 are not both phenyl at the same time, R 3 and R 4 are both hydrogen atoms, R 5 is tert-butyl or phenyl; In general formula (II): R 1 is 4-methylphenyl or phenyl, R 2 is 4-methylphenyl or phenyl, R 3 and R 4 are both hydrogen atoms, R 5 、R 6 and R 7 are selected from the following groups: (1) R 5 and R 6 form a ring, R 5 and R 6 together form a cyclohexyl group, R 7 is p-toluenesulfonyl; (2) R 5 and R 6 do not form a ring, R 5 is tert-butyl or phenyl, R 6 is phenyl, R 7 is p-toluenesulfonyl.

2. The ligand according to claim 1, characterized in that, the ligand is selected from L5, L7 and L8: 。 3. A method for preparing the ligand according to claim 1 or 2, the ligand being a PNNO chiral tetradentate ligand, characterized in that, the synthetic route is as follows: ； ； The ligand is a PNNN tetradentate ligand, and the synthetic route is as follows: 。 4. The method for preparing the ligand according to claim 3, characterized in that, it comprises the following steps: 1) N-Boc glycine S1 undergoes a condensation reaction with chiral amino acid S2 or chiral diamine S6 under certain conditions to obtain amide intermediate S3 or S7, and then the amino Boc protection is removed to obtain ammonia compound S4 or S8. The deprotection reagent is trifluoroacetic acid, methanesulfonic acid, hydrochloric acid, sulfuric acid, phosphoric acid; 2) Starting from Ugi's amine, it undergoes deprotonation with butyllithium and phosphine addition to obtain intermediate chiral aminophosphine, and then the dimethylamino group is replaced by acetoxy group to obtain intermediate acetate; 3) The acetate reacts with the corresponding ammonia compound S4 or S8 in the presence of triethylamine to obtain the corresponding chiral ligand.

5. The method for preparing the ligand according to claim 4, characterized in that, the deprotection reagent is trifluoroacetic acid and hydrochloric acid.

6. A catalyst, characterized in that, it is a complex formed by the ligand according to claim 1 and a transition metal, and the transition metal is selected from Ir.

7. The catalyst according to claim 6, wherein the suitable transition metal precursor comprises [Ir(COD)Cl] 2 .

8. Use of the catalyst according to claim 6 or 7 as a catalyst in an asymmetric hydrogenation reaction.

9. A compound, characterized in that, the structure of the compound is as formula S8-1 below: 。 10. A compound, characterized in that, the structure of the compound is as formula S8-2 below: 。

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