A novel diindole ligand compound, its synthesis method and application

Abstract

The present invention relates to the field of chemical synthesis technology, and relates to a novel diindole ligand compound, its synthesis method and application. This ligand exhibits excellent catalytic effects in asymmetric reactions. Moreover, the present invention improves the harsh reaction conditions in the ligand synthesis route of the prior art, thereby facilitating the reproducible and large-scale synthesis of the ligand of the present invention and realizing the inexpensive synthesis of the advantageous ligand.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and particularly relates to a novel diindole ligand compound, a synthesis method thereof and an application thereof. Background Art

[0002] In the previous research of the applicant of the present invention, a series of ligand compounds were developed, for example:

[0003]

[0004] This ligand is synthesized from m-aminophenol and 2,4-pentanediol through 5 steps. This ligand shows excellent performance in asymmetric reactions, but the synthesis is relatively cumbersome, the reaction conditions used are relatively harsh, the regioselectivity of some reactions is poor, the yield is low, the steps are long, and the separation is difficult, which is not conducive to large-scale preparation. That is, it requires a relatively high cost and will also cause pollution.

[0005] Therefore, based on the existing technology, it is necessary to effectively solve the problem of poor regioselectivity of functionalization in ligand synthesis, so as to solve the problem of difficult separation and purification of ligands from different isomers. In addition, it is necessary to explore new reactions to improve the harsh reaction conditions in the synthesis route, so as to facilitate the reproducible and large-scale synthesis of ligands. Finally, it is necessary to explore new routes to reduce the raw material cost and achieve the inexpensive synthesis of superior ligands. Summary of the Invention

[0006] In view of the problems and difficulties existing in the technology, the present invention provides a ligand compound having the structure of the following formula (I):

[0007] AG = any substituent and hydrogen.

[0008] As a preferred technical solution of the present invention, R2 is selected from substituted or unsubstituted aryl, cycloalkyl;

[0009] n is a natural number from 1 to 6;

[0010] is selected from

[0011] As a preferred technical solution of the present invention, the aryl is selected from benzene ring, naphthalene ring, indole ring, pyridine ring, furan ring, thiophene ring, anthracene ring, quinoline ring, isoquinoline, imidazole ring, thiazole ring, triazole ring, oxazole ring, etc., and the substituent is selected from alkyl, alkoxy, haloalkyl, alkene, alkyne, heteroatom-substituted alkane, and the heteroatom is selected from N, O, S; the cycloalkyl is selected from C 3-8 cycloalkyl;

[0012] N = 1;

[0013] Selected from

[0014] As a preferred technical solution of the present invention, the ligand compound is a diindole ligand compound, selected from:

[0015]

[0016] As a preferred technical solution of the present invention, a complex is formed by the ligand compound and one or more of Ru, Rh, Ir, Cu, Pd, Ni, Co, Zn and used as a catalyst.

[0017] As a preferred technical solution of the present invention, the catalyst is selected from:

[0018] [Ru(L1)(C 6 H 6 )]Cl 2 :

[0019]

[0020] RuCl2(L1)[(R,R)-DPEN)]:

[0021]

[0022] The present invention further provides a method for synthesizing the ligand compound, which is synthesized through the following route:

[0023]

[0024] The present invention further provides the application of the compound in catalytic asymmetric (chiral) reactions, characterized in that the asymmetric reactions include hydrogenation reactions, hydroformylation reactions, hydrosilylation reactions, hydroboration reactions, hydroxyhydrogenation reactions, hydroamination reactions, hydrocyanation reactions, isomerization formylation reactions, hydroaminomethylation reactions, transfer hydrogenation reactions, allylation reactions, olefin metathesis reactions, ring isomerization reactions, Diels - Alder reactions, asymmetric coupling reactions, Aldol reactions, Michael addition reactions, asymmetric epoxidation reactions, kinetic resolutions and [m + n] cyclization reactions to obtain stereoisomers of specific compounds.

[0025] Furthermore, the application includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right - hand compound Y from the left - hand compound X, selected from:

[0026]

[0027]

[0028] Further, the compound Y1 is selected from:

[0029]

[0030] For example, in one embodiment of the present invention, the reaction substrate (1.0 eq.) is added to a reaction flask in a glove box, then methanol is added, and then a newly prepared catalyst [Ru(L1)(C 6 H 6 )]Cl 2 (0.01 eq.) is added. Then the reaction flask is transferred to a high-pressure hydrogenation autoclave, charged with 50 atm of hydrogen, and reacted at room temperature for 36 h. After the reaction is completed, the hydrogen is released, and the solvent is rotary evaporated to obtain the corresponding hydrogenated product.

[0031] The solvents used in the catalytic reaction of the present invention include: methanol, ethanol, isopropanol, and the TON can be 1000.

[0032] Definitions and General Terms

[0033] Certain embodiments of the present invention are now described in detail, and their examples are illustrated by the accompanying structural formulas and chemical formulas. The present invention is intended to cover all alternative, modifications, and equivalent technical solutions, which are all included within the scope of the present invention as defined in the claims. Those skilled in the art should recognize that many methods and materials similar or equivalent to those described herein can be used to practice the present invention. The present invention is in no way limited to the methods and materials described herein. In the case where one or more of the incorporated documents, patents, and similar materials are different from or contradictory to the present application (including but not limited to the defined terms, term applications, described technologies, etc.), the present application shall prevail.

[0034] It should be further recognized that certain features of the present invention are described in multiple independent embodiments for clarity, but can also be provided in combination in a single embodiment. Conversely, various features of the present invention are described in a single embodiment for brevity, but can also be provided separately or in any suitable sub-combination.

[0035] Unless otherwise specified, all scientific and technical terms used in the present invention have the same meaning as commonly understood by those skilled in the art to which the present invention pertains. All patents and published publications referred to in the present invention are incorporated herein by reference in their entirety.

[0036] The term "comprising" is an open-ended expression, that is, it includes the content specified in the present invention, but does not exclude other aspects.

[0037] "Stereoisomers" refer to compounds that have the same chemical structure but differ in the spatial arrangement of atoms or groups. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotational isomers), geometric isomers (cis / trans isomers), atropisomers, and so on.

[0038] "Chirality" refers to a molecule that has the property of not being superimposable on its mirror image.

[0039] Any asymmetric atom (e.g., carbon, etc.) of the compounds disclosed in the present invention can exist in racemic or enantiomerically enriched form, for example, in the form of (R)-, (S)-, or (R,S)-configurations. In certain embodiments, each asymmetric atom has an enantiomeric excess of at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% in terms of the (R)- or (S)-configuration.

[0040] Any mixture of the resulting stereoisomers can be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers based on the differences in the physicochemical properties of the components, for example, by chromatography and / or fractional crystallization.

[0041] As described in the present invention, the compounds of the present invention can optionally be substituted by one or more substituents, such as the compounds of the general formula above, or like the specific examples, subclasses, and a class of compounds included in the examples of the present invention. It should be understood that the term "optionally substituted by..." can be used interchangeably with the term "unsubstituted or substituted by...". Generally, the term "substituted by..." means that one or more hydrogen atoms in the given structure are replaced by specific substituents. Unless otherwise indicated, an optional substituent group can be substituted at each substitutable position of the group. When more than one position in the given structural formula can be substituted by one or more substituents selected from a specific group, the substituents can be the same or different at each position.

[0042] The term "plurality" as used in the present invention includes 2, 3, 4, 5.

[0043] In various parts of this specification, the substituents of the compounds disclosed in the present invention are disclosed according to the group type or range. In particular, the present invention includes each independent secondary combination of each member of these group types and ranges. For example, the term "C1-C6 alkyl" specifically refers to methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl independently disclosed.

[0044] As used herein, the term "alkyl" or "alkyl group" refers to a saturated straight-chain or branched-chain monovalent hydrocarbon group containing 1 to 20 carbon atoms, wherein said alkyl group may optionally be substituted with one or more substituents described herein. Unless otherwise specified in detail, the alkyl group contains 1-20 carbon atoms. In one embodiment, the alkyl group contains 1-12 carbon atoms; in another embodiment, the alkyl group contains 1-6 carbon atoms; in yet another embodiment, the alkyl group contains 1-4 carbon atoms; still in one embodiment, the alkyl group contains 1-3 carbon atoms.

[0045] Examples of alkyl groups include, but are not limited to, methyl (Me, -CH 3 ), ethyl (Et, -CH 2 CH 3 ), n-propyl (n-Pr, -CH 2 CH 2 CH 3 ), isopropyl (i-Pr, -CH(CH 3 )) 2 ), n-butyl (n-Bu, -CH 2 CH 2 CH 2 CH 3 ), isobutyl (i-Bu, -CH 2 CH(CH 3 )) 2 ), sec-butyl (s-Bu, -CH(CH 3 ))CH 2 CH 3 ), tert-butyl (t-Bu, -C(CH 3 )) 3 ), n-pentyl (-CH 2 CH 2 CH 2 CH 2 CH 3 ), 2-pentyl (-CH(CH 3 ))CH 2 CH 2 CH 3 ), 3-pentyl (-CH(CH 2 CH 3 )) 2 ), 2-methyl-2-butyl (-C(CH 3 )) 2 CH 2 CH 3 ), 3-methyl-2-butyl (-CH(CH 3 ))CH(CH 3 )) 2 ), 3-methyl-1-butyl (-CH2 CH 2 CH(CH 3 ) 2 ),2-methyl-1-butyl (-CH 2 CH(CH 3 )CH 2 CH 3 ),n-hexyl (-CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 ),2-hexyl (-CH(CH 3 )CH 2 CH 2 CH 2 CH 3 ),3-hexyl (-CH(CH 2 CH 3 )(CH 2 CH 2 CH 3 )),2-methyl-2-pentyl (-C(CH 3 ) 2 CH 2 CH 2 CH 3 ),3-methyl-2-pentyl (-CH(CH 3 )CH(CH 3 )CH 2 CH 3 ),4-methyl-2-pentyl (-CH(CH 3 )CH 2 CH(CH 3 ) 2 ),3-methyl-3-pentyl (-C(CH 3 )(CH 2 CH 3 ) 2 ),2-methyl-3-pentyl (-CH(CH 2 CH 3 )CH(CH 3 ) 2 ),2,3-dimethyl-2-butyl (-C(CH 3 ) 2 CH(CH 3 ) 2 ),3,3-dimethyl-2-butyl (-CH(CH 3 )C(CH 3 ) 3 ),n-heptyl, n-octyl, and so on.

[0046] The term "alkenyl" refers to a straight-chain or branched-chain monovalent hydrocarbon group containing 2 to 12 carbon atoms, having at least one unsaturated site, i.e., having a carbon-carbon sp2 double bond, wherein the alkenyl group may optionally be substituted by one or more substituents described in the present invention, including the "cis" and "trans" configurations, or the "E" and "Z" configurations. In one embodiment, the alkenyl group contains 2 to 8 carbon atoms; in another embodiment, the alkenyl group contains 2 to 6 carbon atoms; in yet another embodiment, the alkenyl group contains 2 to 4 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl (-CH=CH 2 ) and allyl (-CH 2 CH=CH 2 ), etc.

[0047] The term "alkynyl" refers to a straight-chain or branched-chain monovalent hydrocarbon group containing 2 to 12 carbon atoms, having at least one unsaturated site, i.e., having a carbon-carbon sp triple bond, wherein the alkynyl group may optionally be substituted by one or more substituents described in the present invention. In one embodiment, the alkynyl group contains 2 to 8 carbon atoms; in another embodiment, the alkynyl group contains 2 to 6 carbon atoms; in yet another embodiment, the alkynyl group contains 2 to 4 carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl (-C≡CH), propargyl (-CH 2 C≡CH), 1-propynyl (-C≡C-CH 3 ), etc.

[0048] The term "cycloalkyl" refers to a saturated monocyclic, bicyclic or tricyclic system containing 3 to 12 carbon atoms, which is monovalent or polyvalent. In one embodiment, the cycloalkyl contains 3 to 12 carbon atoms; in another embodiment, the cycloalkyl contains 3 to 8 carbon atoms, such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane; in yet another embodiment, the cycloalkyl contains 3 to 6 carbon atoms. The cycloalkyl group may independently be unsubstituted or substituted by one or more substituents described in the present invention.

[0049] The halogen refers to fluorine, chlorine, bromine, iodine, and halogenation means that hydrogen is replaced by a halogen.

[0050] The beneficial effects of the present invention compared with the prior art include:

[0051] (1) The synthesis steps of the ligand of the present invention are short and the raw materials are inexpensive;

[0052] (2) The operation of the ligand of the present invention as a catalyst is simple;

[0053] (3) The asymmetric reaction of the ligand of the present invention as a catalyst is easy to scale up synthesis, and the yield and purity of the synthesized target product are high. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 , Schematic diagram of the 1H NMR spectrum of the ligand compound L1 of the present invention;

[0055] Figure 2 , Schematic diagram of the 13C NMR spectrum of the ligand compound L1 of the present invention;

[0056] Figure 3 , Schematic diagram of the second 13C NMR spectrum of the ligand compound L1 of the present invention;

[0057] Among them, L1 is Cyclohexyl-C4-Bisindole-Bisphosphine ligand (CC4-BINBP).

[0058] Figure 4 , Schematic diagram of the 1H NMR spectrum of the ligand compound L2 of the present invention;

[0059] Figure 5 , Schematic diagram of the first 13C NMR spectrum of the ligand compound L2 of the present invention;

[0060] Figure 6 , Schematic diagram of the second 13C NMR spectrum of the ligand compound L2 of the present invention.

[0061] Among them, L2 is dioxolane-C4-Bisindole-Bisphosphine ligand (DC4-BINBP). DETAILED DESCRIPTION OF THE INVENTION

[0062] The present invention will be further described in detail below with reference to the drawings and embodiments, but the embodiments of the present invention are not limited thereto.

[0063] Example 1

[0064]

[0065] Dissolve compound 1 (1.0 eq.) in anhydrous acetonitrile, then add compound 2 (2.0 eq.) and CS 2 CO 3 (4.0 eq.) to the reaction solution, and react at 120 °C for 24 hours. After the reaction is completed, pour the reaction solution into water and extract it three times with ethyl acetate. Combine the organic phases, dry them with anhydrous sodium sulfate, and concentrate them by rotary evaporation. The crude reaction product is separated by silica gel column chromatography (EAPE = 100:1) to obtain the pure compound 3.

[0066] 11H NMR (600 MHz, Chloroform-d) δ 7.75 (d, J = 7.9 Hz, 2H), 7.41–7.28 (m, 4H), 7.24–7.22 (m, 2H), 6.77 (s, 2H), 4.03 (d, J = 15.1 Hz, 2H), 3.69 (dd, J = 15.2, 8.6 Hz, 2H), 2.03–1.95 (m, 2H), 1.94–1.89 (m, 2H), 1.68–1.59 (m, 2H), 1.47–1.37 (m, 2H), 1.22–1.16 (m, 2H). 13 13C NMR (151 MHz, Chloroform-d) δ 137.1, 131.9, 128.0, 122.1, 121.0, 120.0, 109.2, 102.6, 49.9, 46.0, 32.4, 26.4.

[0067]

[0068] Under ice bath conditions, compound 3 was dissolved in a mixed solvent of dichloromethane and hexafluoroisopropanol (DCM:HPFI = 4:1), and then 2.2 equivalents of NBS were added to the reaction solution. The reaction was carried out at 0 °C for 1 hour. When the reaction was completed, the solvent was directly evaporated to dryness. The crude reaction product was separated by silica gel column chromatography (EA:PE = 100:1) to obtain pure compound 4.

[0069] 1 1H NMR (400 MHz, Chloroform-d) δ 7.71 (d, J = 7.9 Hz, 2H), 7.45–7.18 (m, 6H), 4.01 (d, J = 15.2 Hz, 2H), 3.54 (dd, J = 15.2, 8.6 Hz, 2H), 1.98–1.78 (m, 4H), 1.53–1.46 (m, 2H), 1.37–1.31 (m, 2H), 1.20–1.01 (m, 2H). 13 13C NMR (101 MHz, Chloroform-d) δ 135.9, 127.5, 127.0, 123.7, 120.8, 120.1, 109.5, 93.5, 50.4, 46.0, 32.4, 26.2. +9.9 (c = 1.0, CH 2 Cl 2 ).

[0070]

[0071] Under anhydrous and anaerobic conditions, compound 4 was dissolved in dry ether, and then the temperature was lowered to -78 °C for reaction. tBuLi (4.4 eq.) was slowly added dropwise to the reaction solution, and the reaction was carried out at -78 °C for 1 hour. Then, diphenylphosphine chloride was slowly added dropwise to the reaction solution. After the addition of diphenylphosphine chloride was completed, the reaction solution was slowly warmed to room temperature and stirred overnight. When the reaction was completed, the reaction solution was poured into a saturated aqueous solution of ammonium chloride, and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The crude reaction product was separated by silica gel column chromatography (EA:PE = 100:1) to obtain the pure compound L1.

[0072] 1 H NMR (400 MHz, Chloroform-d) δ 7.43–7.39 (m, 4H), 7.36–7.34 (m, 2H), 7.28–7.11 (m, 18H), 7.09–7.07 (m, 2H), 6.94–6.90 (m, 2H), 4.07 (d, J = 14.9 Hz, 2H), 3.56 (dd, J = 14.9, 8.6 Hz, 2H), 1.94 (d, J = 12.8 Hz, 2H), 1.86 (d, J = 8.8 Hz, 2H), 1.62–1.55 (m, 2H), 1.39–1.33 (m, 2H), 1.23–1.07 (m, 2H). 13 C NMR (151 MHz, Chloroform-d) δ 139.2–139.1 (m), 138.9–138.4 (m), 137.6, 136.9 (t, J = 3.7 Hz), 132.8 (t, J = 10.2 Hz), 132.1 (t, J = 9.4 Hz), 123.0 (t, J = 3.2 Hz), 127.93 (t, J = 2.8 Hz), 127.7 (t, J = 3.0 Hz), 127.2, 122.9, 122.6, 120.5, 109.7, 108.9, 49.9, 45.6, 32.4, 26.3. 31 P NMR (162 MHz, Chloroform-d) δ –29.7. +6.4 (c = 1.0, CH 2 Cl 2 ).

[0073] Specifically, as shown in Figure 1 、 2 and 3.

[0074] Example 2

[0075] Under anhydrous and anaerobic conditions, compound 4 was dissolved in dry ether, and then the temperature was lowered to -78 °C for reaction. tBuLi (4.4 eq.) was slowly added dropwise to the reaction solution, and the reaction was carried out at -78 °C for 1 hour. Then, diphenylphosphine chloride was slowly added dropwise to the reaction solution. After the addition of diphenylphosphine chloride, the reaction solution was slowly warmed to room temperature and stirred overnight. When the reaction was completed, the reaction solution was poured into saturated aqueous ammonium chloride solution, and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The crude reaction product was separated by silica gel column chromatography (EA:PE = 100:1) to obtain the pure compound L2.

[0076]

[0077] 1 H NMR (400 MHz, Methylene Chloride-d 2 ) δ 7.46–7.44 (m, 2H), 7.39–7.35 (m, 4H), 7.32–7.27 (m, 2H), 7.23–7.15 (m, 6H), 7.09–7.06 (m, 8H), 7.00–6.94 (m, 2H), 4.14 (d, J = 14.9 Hz, 2H), 3.59 (dd, J = 14.9, 8.9 Hz, 2H), 2.37 (s, 6H), 2.30 (s, 6H), 2.00–1.97 (m, 2H), 1.90–1.88 (m, 2H), 1.67–1.57 (m, 2H), 1.47–1.39 (m, 2H), 1.25–1.15 (m, 2H). 13 C NMR (101 MHz, Methylene Chloride-d 2 ) δ 138.9–138.1 (m), 137.7, 137.2, 137.1, 135.8–135.6 (m), 133.4 (t, J = 3.2 Hz), 132.6 (t, J = 10.3 Hz), 132.1 (t, J = 9.6 Hz), 129.8 (t, J = 3.4 Hz), 128.8 (t, J = 3.0 Hz), 128.5 (t, J = 3.1 Hz), 49.9, 45.4, 32.3, 26.3, 21.0, 20.8. 31 P NMR (162 MHz, Methylene Chloride-d 2 ) δ –30.96. +5.2 (c = 1.0, CH 2 Cl 2 ).

[0078] Specifically, as shown in Figure 4 , 5 and 6.

[0079] Example 3

[0080] Under anhydrous and anaerobic conditions, compound 4 was dissolved in dry ether, and then the temperature was lowered to -78 °C for reaction. t BuLi (4.4 eq.) was slowly added dropwise to the reaction solution, and the reaction was carried out at -78 °C for 1 hour. Then diphenylphosphine chloride was slowly added dropwise to the reaction solution. After adding diphenylphosphine chloride, the reaction solution was slowly warmed to room temperature and stirred overnight. When the reaction was completed, the reaction solution was poured into saturated ammonium chloride aqueous solution, and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The crude product of the reaction was separated by silica gel column chromatography (EA:PE = 100:1) to obtain pure compound L3.

[0081]

[0082] 1 H NMR (600 MHz, Chloroform-d) δ 7.94–7.75 (m, 8H), 7.75–7.65 (m, 4H), 7.57–7.56 (m, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.12 (t, J = 7.6 Hz, 2H), 7.02–7.01 (m, 2H), 4.33 (d, J = 14.9 Hz, 2H), 3.69 (dd, J = 14.8, 8.4 Hz, 2H), 2.11–2.09 (m, 2H), 1.99–1.97 (m, 2H), 1.80–1.66 (m, 2H), 1.52–1.49 (m, 2H), 1.36–1.31 (m, 2H). 13 C NMR (151 MHz, Chloroform-d) δ 140.4 (dd, J = 8.5, 6.4 Hz), 139.7–139.0 (m), 138.2 (d, J = 9.8 Hz), 132.3–131.1 (m), 128.3 (t, J = 3.1 Hz), 125.8 (d, J = 2.6 Hz), 124.3, 123.9 (d, J = 2.5 Hz), 122.5 (t, J = 3.6 Hz), 122.4–122.0 (m), 121.1, 120.3 (d, J = 2.6 Hz), 110.9, 104.7, 50.5, 45.6, 32.4, 26.2. 19 F NMR (565 MHz, Chloroform-d) δ –63.3, -63.3. 31 P NMR (243 MHz, Chloroform-d) δ –26.4. –11.9 (c = 1.0, CH 2 Cl 2 ).

[0083] Example 4

[0084] Under anhydrous and anaerobic conditions, compound 4 was dissolved in dry diethyl ether, and then the temperature was lowered to -78 °C for reaction. t BuLi (4.4 eq.) was slowly added dropwise to the reaction solution, and the reaction was carried out at -78 °C for 1 hour. Then, diphenylphosphine chloride was slowly added dropwise to the reaction solution. After adding diphenylphosphine chloride, the reaction solution was slowly warmed to room temperature and stirred overnight. When the reaction was completed, the reaction solution was poured into a saturated ammonium chloride aqueous solution, and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The crude reaction product was separated by silica gel column chromatography (EA:PE = 100:1) to obtain the pure compound L4.

[0085]

[0086] 1 H NMR (400 MHz, Methylene Chloride-d 2 ) δ 8.29 (s, 2H), 7.95–7.71 (m, 4H), 7.66–7.64 (m, 2H), 7.56–7.45 (m, 2H), 7.40–7.37 (m, 4H), 7.33–6.63 (m, 22H), 4.36–4.34 (m, 2H), 3.98–3.70 (m, 2H), 2.03–1.93 (m, 2H), 1.84–1.82 (m, 2H), 1.68–1.54 (m, 2H), 1.36–1.28 (m, 2H), 1.15–1.13 (m, 2H).

[0087] 13 C NMR (151 MHz, Methylene Chloride-d 2 ) δ 139.2, 138.7, 135.7, 135.4, 134.8, 134.2, 133.5, 133.1, 132.3, 131.4, 129.2, 129.0, 127.2, 126.5, 126.2, 126.1, 125.5, 125.49, 123.3, 122.9, 121.0, 110.8, 108.8, 50.9, 46.0, 32.9, 26.9. 31 P NMR (162 MHz, Methylene Chloride-d 2 ) δ –42.24. +170.5 (c = 1.0, CH 2 Cl 2 ).

[0088] Example 5

[0089] Under anhydrous and anaerobic conditions, compound 4 was dissolved in dry ether, and then the temperature was lowered to -78 °C for reaction. t BuLi (4.4 eq.) was slowly added dropwise to the reaction solution, and the reaction was carried out at -78 °C for 1 hour. Then, diphenylphosphorus chloride was slowly added dropwise to the reaction solution. After adding diphenylphosphorus chloride, the reaction solution was slowly warmed to room temperature and stirred overnight. When the reaction was completed, the reaction solution was poured into a saturated ammonium chloride aqueous solution, and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The crude reaction product was separated by silica gel column chromatography (EA:PE = 100:1) to obtain the pure compound L5.

[0090]

[0091] 1 H NMR (600 MHz, Chloroform-d) δ 7.53–7.43 (m, 2H), 7.39–7.38 (m, 2H), 7.25–7.22 (m, 2H), 7.16–7.05 (m, 6H), 6.98–6.92 (m, 2H), 6.89–6.86 (m, 2H), 6.78–6.75 (m, 4H), 6.61 (dd, J = 7.9, 3.3 Hz, 2H), 6.46 (dd, J = 8.0, 3.4 Hz, 2H), 4.19 (d, J = 14.7 Hz, 2H), 3.86 (dd, J = 14.7, 8.6 Hz, 2H), 3.51 (s, 6H), 3.44 (s, 6H), 2.03–2.01 (m, 2H), 1.90–1.89 (m, 2H), 1.59–1.53 (m, 2H), 1.42–1.39 (m, 2H), 1.27–1.14 (m, 2H). 13 C NMR (151 MHz, Chloroform-d) δ 160.6–160.3 (m), 160.3–160.0 (m), 139.3, 138.9 (d, J = 1.7 Hz), 137.2, 134.6, 132.2, 130.9 (t, J = 3.5 Hz), 128.5, 128.2, 126.0 (d, J = 10.0 Hz), 123.5 (d, J = 6.2 Hz), 122.2, 121.8, 120.2, 119.6 (d, J = 8.4 Hz), 110.0, 109.1, 108.4, 108.3, 55.2, 54.5, 49.5, 45.7, 32.7, 26.3. 31 P NMR (243 MHz, Chloroform-d) δ –49.0. +37.0 (c = 1.0, CH 2 Cl 2).

[0092] Example 6

[0093] Under anhydrous and anaerobic conditions, compound 4 was dissolved in dry ether, and then the temperature was lowered to -78 °C for reaction. t BuLi (4.4 eq.) was slowly added dropwise to the reaction solution, and the reaction was carried out at -78 °C for 1 hour. Then diphenylphosphorus chloride was slowly added dropwise to the reaction solution. After adding diphenylphosphorus chloride, the reaction solution was slowly warmed to room temperature and stirred overnight. When the reaction was completed, the reaction solution was poured into a saturated ammonium chloride aqueous solution, and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The crude reaction product was separated by silica gel column chromatography (EA:PE = 100:1) to obtain the pure compound L6.

[0094]

[0095] 1 H NMR (400 MHz, Methylene Chloride-d 2 ) δ 7.45–7.43 (m, 2H), 7.31–7.27 (m, 4H), 7.11–7.06 (m, 4H), 7.01–6.98 (m, 2H), 6.95–6.88 (m, 6H), 6.86–6.82 (m, 2H), 4.14 (d, J = 14.9 Hz, 2H), 3.59 (dd, J = 14.9, 8.8 Hz, 2H), 2.20 (d, J = 5.1 Hz, 24H), 2.00–1.97 (m, 2H), 1.89–1.87 (m, 2H), 1.62–1.59 (m, 2H), 1.44–1.39 (m, 2H), 1.24–1.14 (m, 2H). 13 C NMR (101 MHz, Methylene Chloride-d 2 ) δ 139.8–139.5 (m), 139.5–138.8 (m), 138.2, 137.9 (t, J = 3.2 Hz), 137.4 (t, J = 3.3 Hz), 136.7 (t, J = 3.3 Hz), 131.1 (t, J = 10.3 Hz), 130.7 (t, J = 9.9 Hz), 130.5 (t, J = 3.3 Hz), 130.0, 129.6, 123.2, 123.1, 120.7, 110.6, 109.9 (d, J = 2.6 Hz), 50.4, 46.0, 33.0, 26.9, 21.7, 21.6. 31 P NMR (162 MHz, Methylene Chloride-d 2 ) δ –29.3. +32.5(c = 1.0, CH 2 Cl 2 ).

[0096] Example 7

[0097] Under anhydrous and anaerobic conditions, compound 4 was dissolved in dry diethyl ether, and then the temperature was lowered to -78 °C for reaction. t BuLi (4.4 eq.) was slowly added dropwise to the reaction solution, and the reaction was carried out at -78 °C for 1 hour. Then, diphenylphosphine chloride was slowly added dropwise to the reaction solution. After adding diphenylphosphine chloride, the reaction solution was slowly warmed to room temperature and stirred overnight. When the reaction was completed, the reaction solution was poured into a saturated ammonium chloride aqueous solution, and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The crude reaction product was separated by silica gel column chromatography (EA:PE = 100:1) to obtain the pure compound L7.

[0098]

[0099] 1 H NMR (600 MHz, Chloroform-d) δ 7.94–7.79 (m, 2H), 7.32–7.25 (m, 4H), 7.19–7.14 (m, 2H), 3.88 (d, J = 14.9 Hz, 2H), 3.30 (dd, J = 14.9, 8.2 Hz, 2H), 2.54–2.50 (m, 2H), 2.12–2.08 (m, 2H), 2.00–1.98 (m, 2H), 1.85–1.62 (m, 18H), 1.54–1.46 (m, 6H), 1.40–1.18 (m, 14H), 1.10–0.97 (m, 8H), 0.87–0.83 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 139.5, 136.8, 131.3, 122.6, 121.9, 119.9, 109.7, 108.4, 108.3, 49.3, 45.4, 36.0, 34.7, 33.3, 32.3, 31.6, 30.9, 30.8, 30.7, 30.4, 30.38, 30.3, 27.7, 27.5, 27.45, 27.4, 27.2, 27.15, 27.1, 27.07, 26.7, 26.3, 26.2. 31 P NMR (162 MHz, Chloroform-d) δ –18.5. –0.2 (c = 1.0, CH 2 Cl 2 ).

[0100] Example 8

[0101] Dissolve Compound 1 (1.0 eq.) in anhydrous acetonitrile, then add Compound 5 (2.0 eq.) and CS 2 CO 3 (4.0 eq.) to the reaction solution, and react at 120 °C for 24 hours. After the reaction is completed, pour the reaction solution into water and extract it three times with ethyl acetate. Combine the organic phases, dry them with anhydrous sodium sulfate, and concentrate them by rotary evaporation. The crude reaction product is separated by silica gel column chromatography (EAPE = 100:1) to obtain pure Compound 6.

[0102]

[0103] 1 H NMR (400 MHz, Chloroform-d) δ 7.65–7.63 (m, 2H), 7.43–7.41 (m, 2H), 7.31–7.25 (m, 2H), 7.19–7.13 (m, 2H), 6.72 (s, 2H), 4.64 (d, J = 14.8 Hz, 2H), 3.82–3.76 (m, 2H), 3.61–3.49 (m, 2H), 1.39 (s, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 136.9, 130.6, 127.6, 122.8, 121.02, 120.4, 109.6, 109.2, 107.2, 81.7, 42.3, 26.6. –92.0 (c = 1.0, CH 2 Cl 2 ).

[0104] Under ice bath conditions, dissolve Compound 6 in a mixed solvent of dichloromethane and hexafluoroisopropanol-free (DCM:HPFI = 4:1), then add 2.2 equivalents of NBS to the reaction solution and react at 0 °C for 1 hour. After the reaction is completed, directly concentrate the solvent by rotary evaporation. The crude reaction product is separated by silica gel column chromatography (EA:PE = 100:1) to obtain pure Compound 7.

[0105]

[0106] 1 H NMR (400 MHz, Chloroform-d) δ 7.81–7.70 (m, 2H), 7.55–7.52 (m, 2H), 7.49–7.42 (m, 2H), 7.38–7.31 (m, 2H), 4.76 (d, J = 15.0 Hz, 2H), 3.89–3.83 (m, 2H), 3.53–3.44 (m, 2H), 1.43 (s, 6H). 1313C NMR (101 MHz, Chloroform-d) δ 136.1, 127.3, 125.9, 124.5, 121.3, 120.3, 109.7, 109.65, 98.1, 81.4, 43.1, 26.6. +144.5 (c = 1.0, CH 2 Cl 2 ).

[0107] Under anhydrous and anaerobic conditions, compound 7 was dissolved in dry diethyl ether, and then the temperature was lowered to -78 °C for reaction. t BuLi (4.4 eq.) was slowly added dropwise to the reaction solution, and the reaction was carried out at -78 °C for 1 hour. Then, diphenylphosphine chloride was slowly added dropwise to the reaction solution. After adding diphenylphosphine chloride, the reaction solution was slowly warmed to room temperature and stirred overnight. When the reaction was completed, the reaction solution was poured into a saturated aqueous solution of ammonium chloride, and extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation. The crude reaction product was separated by silica gel column chromatography (EA:PE = 100:1) to obtain the pure compound L8.

[0108]

[0109] 1 1H NMR (400 MHz, Chloroform-d) δ 7.42–7.40 (m, 2H), 7.26–7.23 (m, 10H), 7.10–6.96 (m, 14H), 6.86–6.83 (m, 2H), 4.59 (d, J = 14.7 Hz, 2H), 3.64 (dd, J = 14.5, 8.1 Hz, 2H), 3.27 (d, J = 7.5 Hz, 2H), 1.28 (s, 6H). 13 13C NMR (101 MHz, Chloroform-d) δ 138.3–138.1 (m), 137.9, 136.2–136.0 (m), 132.3 (dt, J = 18.1, 9.5 Hz), 129.8 (t, J = 3.1 Hz), 128.1 (t, J = 3.0 Hz), 127.7 (t, J = 2.9 Hz), 127.6, 127.3, 123.3, 122.8, 121.0, 113.1 (d, J = 3.0 Hz), 110.0, 109.7, 81.2, 42.8, 26.6. 31 31P NMR (162 MHz, Chloroform-d) δ –29.85. +106.9 (c = 1.0, CH 2 Cl 2 ).

[0110] Example 9

[0111] [Ru(L1)(C 6 H 6 )]Cl 2 Preparation:

[0112] In a glove box, ligand L1 (74.3 mg, 0.105 mmol) and [Ru(benzene)Cl] 2 (25 mg, 0.05 mmol) were dissolved in degassed DMF, and then the reaction solution was heated to 100 °C for 10 minutes. After that, the reaction solution was evaporated to dryness to obtain the complex [Ru(L1)(C 6 H 6 )]Cl 2 . This complex can be used in the next reaction without purification.

[0113]

[0114] Example 10

[0115] RuCl 2 (L1)[(R,R)-DPEN)] Preparation:

[0116] In a glove box, ligand L1 (37.2 mg, 0.052 mmol) and [Ru(benzene)Cl] 2 (12.5 mg, 0.025 mmol) were dissolved in degassed DMF, and then the reaction solution was heated to 100 °C for 10 minutes. Then the reaction solution was cooled to room temperature, and (R,R)-DPEN (11.1 mg, 0.052 mmol) was added. At room temperature, the reaction continued for 3 hours. After that, the reaction solution was evaporated to dryness, and 1 mL of dichloromethane was added to the reaction flask. The solid residue was filtered off, and 1 mL of ether was added to the filtrate. The complex RuCl 2 (L1)[(R,R)-DPEN)] precipitated from the solution. The solution was filtered off, and then the solid product was dried under vacuum. This complex can be used in the next reaction without purification.

[0117]

[0118] Example 11

[0119] In a glove box, the reaction substrate (1.0 eq.) was added to the reaction flask, then methanol was added, and then the newly prepared catalyst [Ru(L1)(C 6 H 6 )]Cl 2(0.01 eq.). Then transfer the reaction flask to a high-pressure hydrogenation autoclave, introduce 50 atm of hydrogen, and react at room temperature for 36 h. After the reaction is completed, release the hydrogen and rotary evaporate the solvent to obtain the corresponding hydrogenated product.

[0120]

[0121] 1 H NMR (600 MHz, Chloroform-d) δ 7.61–7.57 (m, 1H), 7.25–7.17 (m, 2H), 7.09–7.07 (m, 1H), 5.05 (d, J = 9.0 Hz, 1H), 4.23 (q, J = 7.1 Hz, 2H), 3.07 (s, 1H), 2.94–2.89 (m, 1H), 2.85–2.81 (m, 1H), 2.71–2.67 (m, 1H), 2.28–2.22 (m, 1H), 1.96–1.86 (m, 1H), 1.31 (t, J = 7.1 Hz, 3H). The hydrogen spectrum and optical rotation are consistent with the literature. 1-2 . –87.2 (c = 1.0, CHCl 3 ). (lit. 2 –116 (c = 1.35, EtOH)). The enantiomeric excess (ee) value is 98%, and the diastereomeric excess (de) value is >99%. The polarity of the Chiralpak OJ-3 chiral column: hexane:isopropanol = 95:5; flow rate = 1.0 mL / min.

[0122]

[0123] 1 H NMR (400 MHz, Chloroform-d) δ 7.39–7.34 (m, 4H), 7.31–7.24 (m, 1H), 5.15–5.11 (m, 1H), 4.18 (q, J = 7.1 Hz, 2H), 3.30 (d, J = 2.7 Hz, 1H), 2.84–2.63 (m, 2H), 1.26 (t, J = 7.1 Hz, 3H). The hydrogen spectrum and optical rotation are consistent with the literature. 3-5 . +38.9 (c = 1.0, CHCl 3 ). (lit. 4 +41.1 (c = 1.0, CHCl 3 ); lit. 5 +40.2 (c = 1.0, CHCl 3The EE value is 98%, using a Chiralpak OJ-H chiral column. The polarity is hexane:isopropanol = 95:5; the flow rate = 1.0 mL / min.

[0124]

[0125] 1 1H NMR (400 MHz, Chloroform-d) δ 4.20–4.12 (m, 3H), 2.51–2.38 (m, 2H), 1.28 (t, J = 7.2 Hz, 3H), 1.23 (d, J = 6.3 Hz, 3H). The 1H NMR and optical rotation are consistent with the literature. 6-7 . +28.8 (c = 1.0, CHCl 3 ). (lit. 6 +42.2 (c = 1.0, CHCl 3 ); lit. 7 +32.3 (c = 2.5, CHCl 3 ).

[0126] The EE value is 92%, measured based on the corresponding benzoyl ester, using a Chiralpak OJ-3 chiral column; the polarity is hexane:isopropanol = 98:2; the flow rate = 1.0 mL / min.

[0127]

[0128] 1 1H NMR (600 MHz, Chloroform-d) δ 4.09–3.88 (m, 1H), 3.68 (s, 3H), 2.94 (s, 1H), 2.51–2.35 (m, 2H), 1.51–1.47 (m, 1H), 1.45–1.35 (m, 2H), 1.32–1.23 (m, 17H), 0.85 (t, J = 7.0 Hz, 3H). The 1H NMR and optical rotation are consistent with the literature. 8-10 . +7.4 (c = 1.0, CHCl 3 ). (lit. 8 +17.9 (c = 1.3, CHCl 3 ), lit. 9 +13.5 (c = 1.0, CHCl 3)). The EE value is 90%, measured based on the corresponding benzoyl ester, using a Chiralpak OD-H chiral column; the polarity is hexane:isopropanol = 99:1; the flow rate = 1.0 mL / min.

[0129]

[0130] 1 H NMR (600 MHz, Chloroform-d) δ 7.76–7.74 (m, 2H), 7.49–7.46 (m, 1H), 7.40–7.38 (m, 2H), 7.14–7.12 (m, 1H), 4.32 (brs, 1H), 4.09–3.97 (m, 2H), 3.69 (s, 3H), 3.58 (dt, J = 14.0, 3.8 Hz, 1H), 2.60 (dt, J = 7.6, 3.9 Hz, 1H), 1.24 (d, J = 6.2 Hz, 3H). The hydrogen spectrum and optical rotation are consistent with the literature. 11-12 . –44.2 (c = 1.0, CHCl 3 ). (lit. 12 –45.3 (c = 1.0, CHCl 3 )). The EE value is 90% and the diastereomeric excess is 82%, using a Chiralpak AD-H chiral column, the polarity is hexane:isopropanol = 85:15; the flow rate = 0.5 mL / min.

[0131] Example 12

[0132]

[0133] In the glove box, add the reaction substrate (1.0 eq.) to the reaction flask, then add methanol, then add salicylic acid (3.0 eq.) and salicylic acid anhydride (1.0 eq.), and finally add the newly prepared catalyst [Ru(L1)(C 6 H 6 )]Cl 2 (0.01 eq.). Then transfer the reaction flask to a high-pressure hydrogenation autoclave, charge 50 atm of hydrogen, and react at 80 °C for 24 h. After the reaction is completed, release the hydrogen and evaporate the solvent to obtain the corresponding hydrogenated product.

[0134] 11H NMR (600 MHz, Chloroform-d) δ 7.04 (q, J = 8.6 Hz, 1H), 6.84 (q, J = 8.8 Hz, 1H), 5.05–4.80 (m, 2H), 4.20–3.89 (m, 4H), 3.58–3.45 (m, 1H), 2.76–2.63 (m, 2H), 2.54–2.44 (m, 2H), 2.30 (brs, 2H). The 1H NMR and optical rotation are consistent with the literature. 13-14 . +19.1 (c = 1.0, CHCl 3 ). (lit. 14 –22.9 (c = 1.0, CHCl 3 ) Enantiomer of Y2. EE value 99%, Chiralpak IC chiral column, polar hexane:ethanol:diethylamine = 80:20:0.1; flow rate = 1.0 mL / min.

[0135] Example 13

[0136]

[0137] In the glove box, the reaction substrate (1.0 eq.) was added to the reaction flask, then toluene was added, followed by [Ir(COD)Cl] 2 (0.01 eq.) and L1 (0.01 eq.), and finally iodine (0.05 eq.) was added. Then the reaction flask was transferred to a high-pressure hydrogenation autoclave, filled with 50 atm of hydrogen, and reacted at 80 °C for 24 h. After the reaction was completed, the hydrogen was released, and the solvent was evaporated to dryness to obtain the corresponding hydrogenated product.

[0138] 1 1H NMR (400 MHz, Chloroform-d) δ 7.04–6.95 (m, 2H), 6.67–6.63 (m, 1H), 6.54–6.48 (m, 1H), 3.56 (brs, 1H), 3.48–3.40 (m, 1H), 2.93–2.84 (m, 1H), 2.80–2.74 (m, 1H), 2.00–1.94 (m, 1H), 1.68–1.58 (m, 1H), 1.25 (d, J = 6.3 Hz, 3H). The 1H NMR and optical rotation are consistent with the literature. 15-16 . –68.8 (c = 1.0, CHCl 3 ). (lit. 16 –66.8 (c = 0.5, CHCl 3)). The EE value is 93%, using a Chiralpak OJ-H chiral column, with a polarity of hexane:isopropanol = 95:5; the flow rate = 1.0 mL / min.

[0139] Example 14

[0140]

[0141] In the glove box, add the reaction substrate (1.0 eq.) to the reaction flask, then add DCE, and then add [Ir(COD)Cl] 2 (0.005 eq.) and L1 (0.01 eq.). Then transfer the reaction flask to a high-pressure hydrogenation autoclave, charge 20 atm of hydrogen, and react at room temperature for 24 h. After the reaction is completed, release the hydrogen and rotary evaporate the solvent to obtain the corresponding hydrogenated product.

[0142] 1 1H NMR (400 MHz, Chloroform-d) δ 7.67–7.63 (m, 4H), 7.35–7.26 (m, 6H), 7.24–7.19 (m, 1H), 7.15–7.10 (m, 3H), 4.78 (dt, J = 10.2, 5.1 Hz, 1H), 4.07–4.06 (m, 1H), 3.60–3.57 (m, 1H), 3.32 (d, J = 14.1 Hz, 1H), 3.18–3.12 (m, 1H), 2.91–2.77 (m, 1H), 2.53 (dt, J = 11.6, 5.1 Hz, 1H), 2.32–2.23 (m, 1H), 1.94–1.87 (m, 1H), 1.79–1.69 (m, 1H). The hydrogen spectrum and optical rotation are consistent with the literature 17 . +33.9 (c = 1.0, CHCl 3 ). (lit. 17 +54.9 (c = 1.0, CHCl 3 )). The EE value is 94%, using a Chiralpak IA chiral column, with a polarity of hexane:isopropanol = 85:15; the flow rate = 0.8 mL / min.

[0143] Example 15

[0144]

[0145] In the glove box, the reaction substrate (1.0 eq.) was added to the reaction flask, followed by isopropanol, potassium tert-butoxide (0.1 eq.), and freshly prepared bisphosphine diamine catalyst (0.01 eq.). Then the reaction flask was transferred to a high-pressure hydrogenation autoclave, filled with 80 atm of hydrogen, and reacted at 60 °C for 24 h. After the reaction was completed, the hydrogen was released, and the solvent was evaporated to dryness to obtain the corresponding hydrogenated product.

[0146] 1 1H NMR (400 MHz, Chloroform-d) δ 7.37–7.28 (m, 2H), 7.28–7.17 (m, 3H), 4.01–3.97 (m, 1H), 2.73 (dt, J = 12.9, 2.8 Hz, 1H), 2.13–1.93 (m, 2H), 1.92–1.83 (m, 1H), 1.72–1.58 (m, 3H), 1.56–1.48 (m, 1H), 1.44–1.25 (m, 2H). The 1H NMR and optical rotation were consistent with the literature. 18-19 . –109.4 (c = 1.0, MeOH). (lit. 19 –109.1 (c = 1.05, MeOH)). The ee value was 99%, the dr value was >99%, Chiralpak AD-H chiral column, polar hexane:isopropanol = 95:5; flow rate = 0.75 mL / min.

[0147] Example 16

[0148]

[0149] In the glove box, Cu(OAc) 2 (7.2 mg, 0.04 mmol) was dissolved in 4 mL of anhydrous toluene, and then L1 (28.4 mg, 0.04 mmol) was added. The reaction solution was stirred at room temperature for 30 minutes. Then PMHS (184 μL, 1.6 mmol) and t BuOH (44 μL, 0.44 mmol) were added to the reaction, and stirring was continued at room temperature for 30 minutes. Then the reaction system was cooled to 0 °C, and the reaction substrate was added, and the reaction was continued at 0 °C for 48 hours. After the reaction was completed, it was quenched with a saturated KF / MeOH solution, extracted three times with dichloromethane, the organic phases were combined, dried over anhydrous sodium sulfate, and evaporated to dryness. The crude reaction product was purified by silica gel column chromatography to obtain the product as a colorless oily compound.

[0150] 1H NMR (400 MHz, Chloroform-d) δ 7.33–7.15 (m, 5H), 4.08 (q, J=7.1 Hz, 2H), 3.35–3.24 (m, 1H), 2.64–2.51 (m, 2H), 1.31 (d, J=7.0 Hz, 3H), 1.18 (t, J=7.1 Hz, 3H).

[0151] Example 17

[0152]

[0153] In the glove box, the reaction substrate (1.0 eq.) was added to the reaction flask, then DCE was added, and then [Rh(COD)Cl] 2 (0.005 eq.) and L1 (0.01 eq.) were added. Finally, AgSbF 6 (0.02 eq.) was added. The reaction was carried out at room temperature for 5 minutes. After the reaction was completed, the hydrogen was released, and the solvent was rotary evaporated and passed through a silica gel column to obtain the corresponding ring isomerization product.

[0154] 1 H NMR (400 MHz, Chloroform-d) δ 7.36–7.19 (m, 4H), 7.17–7.10 (m, 2H), 6.27 (q, J=2.5 Hz, 1H), 5.40–5.27 (m, 1H), 4.79–4.57 (m, 2H), 4.15–4.07 (m, 1H), 3.53–3.43 (m, 2H), 2.16 (s, 3H).

[0155] +182.2 (c=1.0, CHCl 3 ).

[0156] The enantiomeric excess of the product was 99%, determined by HPLC on Chiralpak OD-H column with hexane:isopropanol=99:1; flow rate=1.0 mL / min.

[0157] Example 18

[0158] In the glove box, L1 (12.3 mg, 0.017 mmol), Pd 2 (dba) 3 (7.2 mg, 0.0079 mmol) and the substrate (50 mg, 0.16 mmol) were dissolved in degassed DMF, and then Ag 3 PO4 (133 mg, 0.32 mmol). The reaction was heated to 80 °C and continued for 24 hours. Then the reaction was quenched with water, extracted three times with dichloromethane, the organic phases were combined, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude reaction product was purified by silica gel column chromatography to give the product as a colorless oily compound.

[0159] 1 H NMR (400 MHz, Chloroform-d) δ 7.29–7.27 (m, 1H), 7.24–7.14 (m, 1H), 7.14–7.05 (m, 1H), 6.87 (d, J = 7.8 Hz, 1H), 5.95 (dd, J = 17.2, 10.5 Hz, 1H), 5.20–5.07 (m, 2H), 3.21 (s, 3H), 1.49 (s, 3H).

[0160]

[0161] Example 19

[0162]

[0163] In the glove box, the reaction substrate (1.0 eq.) was added to the reaction flask, then DCE was added, and [Rh(COD)Cl]BF 4 (0.01 eq.) and L1 (0.011 eq.) were added. Then the reaction flask was transferred to a high-pressure hydrogenation autoclave, charged with 20 atm of hydrogen, and reacted at room temperature for 24 h. After the reaction was completed, the hydrogen was released, and the solvent was concentrated in vacuo to obtain the corresponding hydrogenated product.

[0164] 1 H NMR (400 MHz, Chloroform-d) δ 7.31–7.22 (m, 3H), 7.12–7.08 (m, 2H), 6.11 (d, J = 7.4 Hz, 1H), 4.91–4.86 (m, 1H), 3.72 (s, 3H), 3.17–3.05 (m, 2H), 1.97 (s, 3H). The 1H NMR and optical rotation were consistent with the literature. 20 . +59.5 (c = 1.0, CHCl 3 ). (lit 20 . +97.92 (c = 1.0, CHCl 3 ). The enantiomeric excess (ee) was determined on a Chiralpak IA chiral column with a mobile phase of hexane:isopropanol = 90:10; flow rate = 1.0 mL / min.

[0165] Example 18

[0166]

[0167] In the glove box, the reaction substrate (1.0 eq.) was added to the reaction flask, then DCM was added, and then [Rh(NBD)Cl]BF 4 (0.01 eq.) and L1 (0.011 eq.) were added. Then the reaction flask was transferred to a high-pressure hydrogenation autoclave, filled with 100 atm of hydrogen, and reacted at room temperature for 6 h. After the reaction was completed, the hydrogen was released, and the solvent was evaporated to dryness to obtain the corresponding hydrogenated product.

[0168] 1 1H NMR (600 MHz, Chloroform-d) δ 6.15 (br, 1H), 4.38–4.29 (m, 1H), 4.17–4.10 (m, 2H), 2.53–2.45 (m, 2H), 1.94 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H), 1.21 (d, J = 6.8 Hz, 3H). The hydrogen spectrum and optical rotation are consistent with the literature. 21 . The ee value was measured on a Chiralpak OJ-H chiral column with a polarity of hexane:isopropanol = 95:5; flow rate = 0.5 mL / min.

[0169] It is easy for those skilled in the art to understand that the above are only the preferred embodiments of the present invention and are not used to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principle of the present invention should be included within the protection scope of the present invention.

[0170] References for the identification of the compound are as follows:

[0171] 1. Ros, A.; Magriz, A.; Dietrich, H.; Lassaletta, J.M.; Fernández, R., Stereoselective synthesis of syn β-hydroxy cycloalkane carboxylates: transfer hydrogenation of cyclic β-keto esters via dynamic kinetic resolution. Tetrahedron 2007, 63(32), 7532-7537.

[0172] 2. Buisson, D.; Cecchi, R.; Laffitte, J.-A.; Guzzi, U.; Azerad, R., Microbial reduction of 1-tetralone 2-carboxyesters as a source of new asymmetric synthons. Tetrahedron Lett. 1994, 35(19), 3091-3094.

[0173] 3. Yuan, Y.; Li, X.; Sun, J.; Ding, K., To probe the origin of activation effect of carboxylic acid and (+)-NLE in tridentated titanium catalyst systems. J. Am. Chem. Soc. 2002, 124(50), 14866-14867.

[0174] 4. Tian, C.; Gong, L.; Meggers, E., Chiral-at-metal iridium complex for efficient enantioselective transfer hydrogenation of ketones. Chem. Commun. 2016, 52(22), 4207-4210.

[0175] 5. Koszelewski, D.; Zysk, M.; Brodzka, A.; Zadlo, A.; Paprocki, D.; Ostaszewski, R., Evaluation of a new protocol for enzymatic dynamic kinetic resolution of 3-hydroxy-3-(aryl)propanoic acids. Org. Biomol. Chem. 2015, 13(45), 11014-11020.

[0176] 6. Fernandes, R.A.; Mulay, S.V., Total synthesis of (+)-demethoxycardinalin 3. J. Org. Chem. 2010, 75(20), 7029-7032.

[0177] 7. Rodriguez, S.; Kayser, M. M.; Stewart, J. D., Highly stereoselective reagents for beta-keto ester reductions by genetic engineering of baker's yeast. J. Am. Chem. Soc. 2001, 123(8), 1547 - 1555.

[0178] 8. Case-Green, S. C.; Davies, S. G.; Roberts, P. M.; Russell, A. J.; Thomson, J. E., Asymmetric synthesis of tetrahydrolipstatin and valilactone. Tetrahedron: Asymmetry 2008, 19(22), 2620 - 2631.

[0179] 9. Kücük, H. B.; A., Enantioselective synthesis of 3-hydroxytetradecanoic acid and its methyl ester enantiomers as new antioxidants and enzyme inhibitors. Monatsh. Chem. 2013, 144(7), 1087 - 1091.

[0180] 10. Lin, Z.; Li, J.; Huang, Q.; Huang, Q.; Wang, Q.; Tang, L.; Gong, D.; Yang, J.; Zhu, J.; Deng, J., Chiral Surfactant-Type Catalyst: Enantioselective Reduction of Long-Chain Aliphatic Ketoesters in Water. J. Org. Chem. 2015, 80(9), 4419 - 4429.

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Claims

1. A ligand compound, characterized in that, it has the structure of the following formula (I): wherein, AG is selected from hydrogen, n is 1, and R is selected from monocyclic aryl, polycyclic aryl or cycloalkyl; The said Selected from 2. The ligand compound according to claim 1, characterized in that, the R is selected from monocyclic aryl, and any hydrogen on the monocyclic aryl is substituted by an alkyl group having 1 to 4 carbons, a haloalkyl group having 1 to 4 carbons, or an alkoxy group having 1 to 4 carbons.

3. The ligand compound according to claim 1, characterized in that, the polycyclic aryl is selected from naphthyl.

4. The ligand compound according to claim 1, characterized in that, the ligand compound is a diindole ligand compound, selected from:

5. A catalyst, characterized in that a complex is formed by the ligand compound according to any one of claims 1 to 4 and Ru, Rh, Ir, Cu, Pd and used as a catalyst.

6. The catalyst according to claim 5, characterized in that, the catalyst is selected from: [Ru(L1)(C 6 H 6 )]Cl 2 : RuCl 2 (L1)[(R,R)-DPEN)]:

7. A method for synthesizing the ligand compound according to any one of claims 1 to 4, characterized in that, it is synthesized through the following route: the R is defined as in any one of claims 1 to 4.

8. The application of the catalyst according to claim 5 or 6 in a catalytic asymmetric reaction, characterized in that, the asymmetric reaction includes a hydrogenation reaction and a ring isomerization reaction.

9. The application according to claim 8, characterized in that, it includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right compound Y1 from the left compound X1: the compound Y1 is selected from: R on the X1 1 corresponds to Y1; The X1 is obtained as Y1 under the action of the catalyst [Ru(L1)(C 6 H 6 )]Cl 2 .

10. The application according to claim 8, characterized in that, it includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right compound Y2 from the left compound X2: The X2 is obtained as Y2 under the action of the catalyst [Ru(L1)(C 6 H 6 )]Cl 2 .

11. The application according to claim 8, characterized in that, it includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right compound Y3 from the left compound X3: The X3 is obtained as Y3 under the action of the catalyst [Ir(COD)Cl] 2 / L1, and the catalyst [Ir(COD)Cl] 2 / L1 is obtained by complexing [Ir(COD)Cl] 2 and L1 in an organic solvent.

12. The application according to claim 8, characterized in that, it includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right compound Y4 from the left compound X4: The X4 is reacted under the action of the catalyst [Ir(COD)Cl] 2 / L1 to obtain Y4, and the catalyst [Ir(COD)Cl] 2 / L1 is obtained by complexing [Ir(COD)Cl] 2 and L1 in an organic solvent.

13. The application according to claim 8, characterized in that, it includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right compound Y5 from the left compound X5: The X5 is obtained as Y5 under the action of the catalyst RuCl 2 (L1)[(R,R)-DPEN)] or RuCl 2 (L1)[(S,S)-DPEN)].

14. The application according to claim 8, characterized in that, it includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right compound Y6 from the left compound X6: The X6 is converted to Y6 under the action of the catalyst Cu(OAc) 2 / L1.

15. The application according to claim 8, characterized in that, it includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right compound Y7 from the left compound X7: X7 is obtained from Y7 under the action of a catalyst, and the catalyst is obtained by complexing [Rh(COD)Cl] 2 and L1 in an organic solvent.

16. The application according to claim 8, characterized in that, it includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right compound Y8 from the left compound X8: The X8 is converted to Y8 under the action of a catalyst, and the catalyst is obtained by complexing Pd 2 (dba) 3 and L1 in an organic solvent.

17. The application according to claim 8, characterized in that, it includes carrying out a catalytic asymmetric reaction using the catalyst to obtain the right compound Y9 from the left compound X9: The X9 is obtained to be Y9 under the action of a catalyst, and the catalyst is obtained by complexing one of L1, L2, L5, L6 and L8 with [Rh(COD) 2 BF 4 in an organic solvent.

18. The application according to claim 8, characterized in that, Including performing a catalytic asymmetric reaction using the said catalyst to obtain a right-handed compound Y10 from a left-handed compound X10: X10 is obtained under the action of a catalyst, and the catalyst is obtained by complexing one of L1, L2, L3, and L8 with [Rh(NBD) 2 BF 4 in an organic solvent.

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