Methods for preparing 1-tetrahydronaphthol derivatives and chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives

Abstract

This invention relates to the field of organic synthesis, specifically to a method for preparing 1-tetrahydronaphthone derivatives and chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives. The method includes hydrogenating a 1-naphthol derivative with a hydrogen source in the presence of a chiral diamine metal catalyst to obtain a 1-tetrahydronaphthone derivative; and then adding a reducing solvent to the aforementioned hydrogenated reaction solution to perform a chiral reduction reaction to obtain a chiral 1-tetrahydronaphthol derivative. The 1-naphthol derivative is a compound of formula (1), the 1-tetrahydronaphthone derivative is a compound of formula (2), and the chiral 1-tetrahydronaphthol derivative is a compound of formula (3). This method has a wide range of applicable substrates, is simple to operate, and exhibits unprecedented high yield and selectivity, providing a new method for synthesizing 1-tetrahydronaphthone derivatives and chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives. Formula (1) Formula (2) Formula (3)

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and specifically to a method for preparing 1-tetrahydronaphthone derivatives and chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives. Background Technology

[0002] Since its first report in 1936, the hydrogenation reduction of 1-naphthol derivatives has attracted much attention. The reduction products of 1-naphthol, 1-tetrahydronaphthone and 1-tetrahydronaphthol, are important structural units in many natural products and crucial building blocks in organic synthesis. Therefore, in the past few decades, various heterogeneous catalysts based on different metals (e.g., copper, nickel, palladium, rhodium, ruthenium, platinum, etc.) have been developed. However, most reported heterogeneous catalysts still suffer from low selectivity and poor functional group tolerance. Only a few catalysts have been found to be effective for the transfer hydrogenation of 1-naphthol derivatives (V. Trombettoni, F. Ferlin, F. Valentini, F. Campana, M. Silvetti, L. Vaccaro, Mol. Catal. 2021, 509, 111613; X. Li, W. Hao, N. Yi, Y.-M. He, Q.-H. Fan, CCS). (Chem. 2023, 5, 2277; Y. He, J. Tang, M. Luo, X. Zeng, Org. Lett. 2018, 20, 4159; Y. Wang, Z. Chang, Y. Hu, X. Lin, X. Dou, Org. Lett. 2021, 23, 1910). Transfer hydrogenation has proven to be a practical and efficient reduction method, but examples of heterogeneous transfer hydrogenation of 1-naphthol derivatives are scarce. Therefore, there is a great need to develop new homogeneous catalytic systems and / or novel strategies to achieve such challenging conversions while avoiding the use of high-pressure hydrogen. To date, only a few cases have been reported on the highly selective yield of ketone products via transfer hydrogenation, and all of them used Pd-based heterogeneous catalysts (V. Trombettoni, F. Ferlin, F. Valentini, F. Campana, M. Silvetti, L. Vaccaro, Mol. Catal. 2021, 509, 111613; X. Li, W. Hao, N. Yi, Y.-M. He, Q.-H. Fan, CCS Chem. 2023, 5, 2277). Only one case has been reported on the tandem reaction of naphthol to obtain chiral alcohol products via transfer hydrogenation (X. Li, W. Hao, N. Yi, Y.-M. He, Q.-H. Fan, CCS Chem. 2023, 5, 2277), but it was achieved through heterogeneous / homogeneous relay catalysis and had substrate limitations. Therefore, to this day, the precise control of the chemoselectivity, regioselectivity and enantioselectivity of 1-naphthol derivatives through homogeneous catalysis to obtain 1-tetrahydronaphthone derivatives and chiral 1-tetrahydronaphthol derivatives remains an unresolved challenge and a problem that needs to be solved in this field. Summary of the Invention

[0003] The purpose of this invention is to overcome the problems existing in the prior art and provide a method for preparing 1-tetrahydronaphthone derivatives and chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives. This method has a wide range of applicable substrates, is simple to operate, and exhibits unprecedented high yield and high selectivity.

[0004] To achieve the above objectives, the first aspect of the present invention provides a method for preparing a 1-tetrahydronaphthone derivative from a 1-naphthol derivative. The method includes hydrogenating the 1-naphthol derivative with a hydrogen source in the presence of a chiral diamine metal catalyst to obtain the 1-tetrahydronaphthone derivative. The 1-naphthol derivative is a compound of formula (1), and the 1-tetrahydronaphthone derivative is a compound of formula (2).

[0005] Equation (1) Equation (2)

[0006] Wherein, A is a benzene ring or a naphthalene ring, and R1 is selected from one or more of H, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C1-C12 alkoxy, substituted or unsubstituted C3-C12 cycloalkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-C12 acyl, substituted or unsubstituted C2-C12 ester, substituted or unsubstituted amino, halogen, and hydroxyl, wherein the substituted C1-C12 alkyl, substituted C1-C12... The substituents of the alkoxy group, the substituted C3-C12 cycloalkyl group, the substituted C6-C20 aryl group, the substituted C1-C12 acyl group, the substituted C2-C12 ester group, and the substituted amino group are each independently selected from one or more of the following: C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C6-C14 aryl, C1-C6 acyl, C2-C6 ester, amino, halogen, and hydroxyl; R2 is selected from one or more of H and C1-C12 alkyl.

[0007] The second aspect of the present invention provides a method for preparing a chiral 1-tetrahydronaphthol derivative from a 1-naphthol derivative. The method includes hydrogenating the 1-naphthol derivative with a hydrogen source in the presence of a chiral diamine metal catalyst, and adding a reducing solvent to carry out a chiral reduction reaction to obtain a chiral 1-tetrahydronaphthol derivative. The 1-naphthol derivative is a compound of formula (1), and the chiral 1-tetrahydronaphthol derivative is a compound of formula (3).

[0008] Equation (1) Equation (3)

[0009] The chiral diamine metal catalyst, the hydrogen source, the hydrogenation treatment, and the compound of formula (1) are as defined in the method of the first aspect above.

[0010] This invention achieves the reduction of 1-naphthol derivatives to 1-tetrahydronaphthone derivatives by providing a specific hydrogen source and using a chiral diamine metal catalyst for transfer hydrogenation. Furthermore, by simply adding a reducing solvent to change the solvent composition, a further chiral reduction reaction can occur under the same catalyst, enantioselectively preparing chiral 1-tetrahydronaphthol derivatives. The method of this invention has a wide substrate applicability, is simple and easy to operate, operates under mild conditions, is highly efficient, exhibits excellent chemoselectivity and enantioselectivity, and achieves unprecedentedly high yields, providing a new method for the synthesis of 1-tetrahydronaphthone derivatives and chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives. Detailed Implementation

[0011] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0012] In this invention, "substituted or unsubstituted C1-C12 alkyl" means that the alkyl group has 1 to 12 carbon atoms, and the H atoms on these carbon atoms may or may not be substituted by substituents; when substituted, the substituted H atoms may be one or more, and when multiple H atoms are substituted, they may be H atoms on the same carbon atom or H atoms on different carbon atoms. Other similar expressions are similar.

[0013] In this invention, the alkyl group in expressions such as "C1-C12 alkyl" and "C1-C6 alkyl" can be either straight-chain alkyl or branched alkyl. The same applies to other similar expressions, such as the alkyl portion in "C1-C6 alkoxy," which can be straight-chain or branched; the alkyl portion in "C6-C20 aryl," which can be straight-chain or branched; and other similar expressions such as "C1-C12 cycloalkyl."

[0014] In this invention, The substituent R1 in the ring A has multiple substitution sites, and can substitute only one site or substitute multiple sites at the same time. When multiple sites are substituted at the same time, the choice of groups for each R1 is independent, and they can be the same or different. The same applies to substituent R2, and the same applies to other identical structures.

[0015] In this invention, The asterisk (*) in the structural formula represents the chiral center, which can be configured as R or S.

[0016] The first aspect of the present invention provides a method for preparing a 1-tetrahydronaphthone derivative from a 1-naphthol derivative, the method comprising hydrogenating the 1-naphthol derivative with a hydrogen source in the presence of a chiral diamine metal catalyst to obtain a 1-tetrahydronaphthone derivative, wherein the 1-naphthol derivative is a compound of formula (1) and the 1-tetrahydronaphthone derivative is a compound of formula (2).

[0017] Equation (1) Equation (2)

[0018] Wherein, A is a benzene ring or a naphthalene ring, and R1 is selected from one or more of H, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C1-C12 alkoxy, substituted or unsubstituted C3-C12 cycloalkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-C12 acyl, substituted or unsubstituted C2-C12 ester, substituted or unsubstituted amino, halogen, and hydroxyl, wherein the substituted C1-C12 alkyl, substituted C1-C12... The substituents of the alkoxy group, the substituted C3-C12 cycloalkyl group, the substituted C6-C20 aryl group, the substituted C1-C12 acyl group, the substituted C2-C12 ester group, and the substituted amino group are each independently selected from one or more of the following: C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C6-C14 aryl, C1-C6 acyl, C2-C6 ester, amino, halogen, and hydroxyl; R2 is selected from one or more of H and C1-C12 alkyl.

[0019] According to the present invention, in order to facilitate the reaction and obtain a higher reaction yield, the selection of functional groups of the compounds shown in formulas (1) and (2) can be adjusted. Preferably, A is a benzene ring or a naphthalene ring, and R1 is selected from H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C14 aryl, substituted or unsubstituted C1-C6 acyl, substituted or unsubstituted C2-C6 ester, substituted or unsubstituted amino, halogen, and hydroxyl. Or a variety of them, wherein the substituents of the substituted C1-C6 alkyl, substituted C1-C6 alkoxy, substituted C3-C6 cycloalkyl, substituted C6-C14 aryl, substituted C1-C6 acyl, substituted C2-C6 ester, and substituted amino are each independently selected from one or more of the following: C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, C6-C14 aryl, C1-C3 acyl, C2-C3 ester, amino, halogen, and hydroxyl; R2 is selected from one or more of H and C1-C6 alkyl.

[0020] More preferably, A is a benzene ring or a naphthalene ring, and R1 is selected from one or more of H, substituted or unsubstituted C1-C3 alkyl groups, substituted or unsubstituted C1-C3 alkoxy groups, substituted or unsubstituted C3-C6 cycloalkyl groups, substituted or unsubstituted C6-C14 aryl groups, substituted or unsubstituted C1-C3 acyl groups, substituted or unsubstituted C2-C3 ester groups, substituted or unsubstituted amino groups, halogens, and hydroxyl groups, wherein the substituted C1-C3 alkyl groups, substituted C1-C3 alkoxy groups, substituted C2-C3 alkoxy groups, substituted or unsubstituted amino groups, halogens, and hydroxyl groups are selected from one or more of H, substituted or unsubstituted C1-C3 alkyl groups, substituted or unsubstituted C1-C3 alkoxy groups, substituted or unsubstituted C2-C3 alkoxy groups, substituted or unsubstituted amino groups, halogens, and hydroxyl groups. The substituents of the alkoxy group, the substituted C3-C6 cycloalkyl group, the substituted C6-C14 aryl group, the substituted C1-C3 acyl group, the substituted C2-C3 ester group, and the substituted amino group are each independently selected from one or more of the following: C1-C3 alkyl group, C1-C3 alkoxy group, C3-C6 cycloalkyl group, C6-C14 aryl group, C1-C3 acyl group, C2-C3 ester group, amino group, halogen group, and hydroxyl group; R2 is selected from one or more of the following: H group and C1-C3 alkyl group.

[0021] More preferably, A is a benzene ring or a naphthyl ring, R1 is selected from one or more of H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, benzyl, formyl, acetyl, propionyl, methyl ester, ethyl ester, amino, F, Cl, Br, hydroxy, aminomethyl, aminoethyl, hydroxymethyl, hydroxyethyl, trifluoromethyl, benzyloxy, formamide, acetamide, propionamide, methyl ester, and ethyl ester; R2 is selected from one or more of H, methyl, ethyl, n-propyl, and isopropyl.

[0022] According to a preferred embodiment of the present invention, the 1-naphthol derivative is selected from one or more compounds represented by the following formula:

[0023]

[0024] According to a preferred embodiment of the present invention, the 1-tetrahydronaphthone derivative is selected from one or more compounds of the following formula:

[0025]

[0026]

[0027] According to a particularly preferred embodiment of the present invention, in the method for preparing 1-tetrahydronaphthone derivatives from 1-naphthol derivatives, the 1-naphthol derivative is selected from one or more compounds represented by formulas (1-1), (1-4), (1-5), (1-6), (1-7), (1-9), (1-10), (1-11), (1-12), (1-13), (1-18), (1-19), (1-20), (1-21), and (1-22). Accordingly, the 1-tetrahydronaphthone derivative is selected from one or more compounds shown in formula (2-1), formula (2-4), formula (2-5), formula (2-6), formula (2-7), formula (2-9), formula (2-10), formula (2-11), formula (2-12), formula (2-13), formula (2-18), formula (2-19), formula (2-20), formula (2-21) and formula (2-22).

[0028] According to the present invention, 1-naphthol derivatives contain substituents with various electronic properties and steric hindrances, making it very challenging to achieve precise control of the chemoselectivity, regioselectivity, and enantioselectivity of 1-naphthol derivatives in reduction reactions. However, the inventors of the present invention have provided a new method that not only achieves the preparation of 1-tetrahydronaphthone derivatives from 1-naphthol derivatives, but also successfully prepares chiral 1-tetrahydronaphthol derivatives by changing the solvent composition and carrying out continuous reactions, and both reactions have high yields.

[0029] According to the present invention, in order to achieve precise control of the reduction reaction of 1-naphthol derivatives, promote the reaction and obtain a good yield, preferably, the chiral diamine metal catalyst is selected from one or more compounds shown in formula (4) and formula (5):

[0030] Equation (4) Equation (5)

[0031] In this context, each metal M is independently selected from one or more of ruthenium, rhodium, and iridium; each L1 is independently selected from substituted or unsubstituted η. 6 -Benzene coordination group and substituted or unsubstituted η 5 - One or more of the cyclohexene coordination groups, and the substituents optionally present in L1 are each independently selected from one or more of the C1-C6 alkyl groups; L2 is selected from C1-C6 oxyalkylene groups, C1-C6 sulfalkylene groups, and One or more of them, wherein R x Selected from one or more alkylene groups of C1-C3, R y Selected from one or more of H, C1-C3 alkoxy groups, and halogens; X is independently selected from Cl. - ,Br- I - CH3COO - NO3 - HSO4 - H2PO4 - BF4 - SbF6 - PF6 - X comprises one or more of the following: bis(trifluoromethanesulfonyl)imide anion, trifluoromethanesulfonic acid anion, substituted or unsubstituted C24-C32 tetraarylboron anion, substituted or unsubstituted C12-C36 diarylphosphate anion and substituted or unsubstituted C12-C36 biaryldiol-derived phosphate anion, wherein the substituents optionally present in X are each independently selected from one or more of the following: C1-C3 alkyl, C1-C3 alkoxy, C1-C3 amide, halogen, nitro, trifluoromethyl and hydroxyl.

[0032] More preferably, each of the metals M is independently selected from one or more of ruthenium, rhodium, and iridium; each of the metals L1 is independently selected from η. 6 -Benzene ligand, η 6 -1,4-Dimethylbenzene ligand, η 6 -1-Methyl-4-isopropylphenyl ligand, η 6 -1,3,5,-Trimethylbenzene ligand, η 6 -1,2,3,4,5-pentamethylbenzene ligand, η 6 -1,2,3,4,5,6-Hexamethylbenzene ligand, η 5 -Maocene ligand and eta 5 - One or more of the pentamethylcenyl ligands; L2 is selected from -CH2-O-CH2-CH2-, -CH2-O-CH2-CH2-CH2-CH2-, -CH2-S-CH2-CH2- and One or more of them, wherein R x Selected from methylene or ethylene, R y Selected from one or more of H, methoxy, ethoxy, F, Cl, and Br; X is independently selected from Cl. - BF4 - SbF6 - PF6 -X is selected from one or more of the following: bis(trifluoromethanesulfonyl)imide anion, trifluoromethanesulfonic acid anion, substituted or unsubstituted C24-C32 tetraarylboron anion, substituted or unsubstituted C12-C36 diarylphosphate anion, and substituted or unsubstituted C12-C36 biaryldiol-derived phosphate anion, wherein the substituents optionally present in X are each independently selected from one or more of methyl, ethyl, methoxy, ethoxy, acetamido, F, Cl, Br, nitro, trifluoromethyl, and hydroxy.

[0033] More preferably, each of the metals M is independently selected from one or more of ruthenium, rhodium, and iridium; each of the metals L1 is independently selected from η. 6 -Benzene ligand, η 6 -1-Methyl-4-isopropylphenyl ligand, η 6 -1,2,3,4,5,6-hexamethylbenzene ligand and eta 5 -One or more of the pentamethylcenyl ligands; L2 is selected from... One or more of them; X is independently selected from Cl. - BF4 - PF6 - SbF6 - One or more of the following: di(trifluoromethanesulfonyl)imide anion, trifluoromethanesulfonic acid anion, tetraphenylboron anion, tetra[3,5-di(trifluoromethyl)phenyl]boron anion, diphenyl phosphate anion, di-p-methylphenyl phosphate anion, di(2,4,6-trimethylphenyl) phosphate anion, di-p-methoxyphenyl phosphate anion, di-p-fluoromethylphenyl phosphate anion, di-p-trifluoromethylphenyl phosphate anion, 2,2'-biphenyl phosphate anion, (R)-2,2'-bi-naphthyl phosphate anion, (S)-2,2'-bi-naphthyl phosphate anion, (R)-8H-2,2'-bi-naphthyl phosphate anion, and (S)-8H-2,2'-bi-naphthyl phosphate anion.

[0034] According to the present invention, the groups in formula (4) and formula (5) are each independently selected from the representations. That is, the groups in formula (4) and formula (5) that are also represented by metals M, L1, X, R' and R” can be the same or different. For example, when X in formula (4) is selected from BF4 - In this case, X in equation (5) can be BF4. - It can also be selected from other groups such as Cl. - SbF6 - PF6 - Examples include bis(trifluoromethanesulfonyl)imide anions and trifluoromethanesulfonic acid anions.

[0035] According to the present invention, the chiral diamine metal catalyst is a ruthenium (Ru), rhodium (Rh), or iridium (Ir) complex with the structure shown in formulas (4) and (5), wherein formula (6) is one of the ligands. It is formed by the diamine NHR”-linker arm -NHSO2R', wherein the N at one end of -NHSO2R' forms a covalent bond with the metal M, while the N at one end of NHR”- forms a coordinate bond with the metal M, thereby forming the compounds shown in formula (4) and formula (5). The linker arm in the diamine NHR”-linker arm -NHSO2R' can make the carbon atom connected to the N at the NHR”-end and / or the carbon atom connected to the N at the -NHSO2R' end of the linker arm a chiral center, thereby making the compounds with the structures shown in formula (4) and formula (5) have a certain catalytic selectivity.

[0036] According to the present invention, the ligands in equations (4) and (5) are defined For formula (6), the compound forming the ligand shown in formula (6) is selected from one or more of the compounds shown in the following formulas:

[0037] Formula (I-1) Formula (I-2) Formula (I-3)

[0038] Formula (I-4) Formula (I-5) Formula (I-6)

[0039] Formula (I-7) Formula (I-8) Formula (I-9)

[0040] Ar1 and Ar2 are each independently selected from one or more of substituted or unsubstituted phenyl groups and substituted or unsubstituted naphthyl groups, and the substituents optionally present in Ar1 and Ar2 are each independently selected from one or more of C1-C3 alkyl groups, C1-C3 alkoxy groups, C1-C3 hydroxyalkyl groups, halogens, hydroxyl groups and carboxyl groups.

[0041] R is selected from one or more of C1-C8 alkyl, trifluoromethyl, substituted or unsubstituted phenyl and substituted or unsubstituted naphthyl groups, and the substituents optionally present in R are each independently selected from one or more of C1-C8 alkyl, methoxy, F, Cl, Br, nitro and trifluoromethyl groups.

[0042] R' is independently selected from one or more of C1-C10 alkyl, trifluoromethyl, substituted amino, substituted or unsubstituted phenyl and substituted or unsubstituted naphthyl groups, and the substituents optionally present in R' are independently selected from one or more of C1-C10 alkyl, methoxy, F, Cl, Br, nitro and trifluoromethyl groups.

[0043] R” is independently selected from one or more of H, substituted or unsubstituted benzyl and C1-C10 alkyl, and the substituents optionally present in R” are independently selected from one or more of C1-C10 alkyl, methoxy, F, Cl, Br, nitro and trifluoromethyl.

[0044] According to the present invention, the compounds with the structure shown in formula (I-1) above are (R,R)-N-monosulfonyl-diarylethylenediamine compounds, and examples of such compounds include:

[0045] Equation (R,R)-(I-1-1-1) Equation (R,R)-(I-1-1-2)

[0046] Equation (R,R)-(I-1-1-3) Equation (R,R)-(I-1-1-4)

[0047] Equation (R,R)-(I-1-1-5) Equation (R,R)-(I-1-1-6)

[0048] Equation (R,R)-(I-1-1-7) Equation (R,R)-(I-1-1-8)

[0049] Compounds with the structure shown in formula (I-2) above are (R,R)-N-monosulfonyl-cyclohexanediamine compounds. Examples of such compounds include:

[0050] Equation (R,R)-(I-2-1-1) Equation (R,R)-(I-2-1-2)

[0051] The compounds with the structure shown in formula (I-3) above are (R,R)-N-monosulfonyl-1-substituted pyrrole-3,4-diamine compounds.

[0052] The compounds with the structure shown in formula (I-4) above are (R)-N-monosulfonyl-2,2'-diamino-1,1'-binaphthyldiamine compounds.

[0053] Compounds with the structure shown in formula (I-5) above are (S,S)-N-monosulfonyl-diarylethylenediamine compounds. Examples of such compounds include:

[0054] Equation (S,S)-(I-5-1-1) Equation (S,S)-(I-5-1-2)

[0055] Equation (S,S)-(I-5-1-3) Equation (S,S)-(I-5-1-4)

[0056] Equation (S,S)-(I-5-1-5) Equation (S,S)-(I-5-1-6)

[0057] Equation (S,S)-(I-5-1-7) Where iPr represents isopropyl.

[0058] Compounds with the structure shown in formula (I-6) above are (S,S)-N-monosulfonyl-cyclohexanediamine compounds. Examples of such compounds include:

[0059] Equation (S,S)-(I-6-1-1) Equation (S,S)-(I-6-1-2)

[0060] The compounds with the structure shown in formula (I-7) above are (S,S)-N-monosulfonyl-1-substituted pyrrole-3,4-diamine compounds.

[0061] The compounds with the structure shown in formula (I-8) above are (S)-N-monosulfonyl-2,2'-diamino-1,1'-binaphthyldiamine compounds.

[0062] The compounds with the structure shown in formula (I-9) above are non-chiral monosulfonyl ethylenediamine compounds.

[0063] According to the present invention, in the compounds with the structures shown in formulas (4) and (5) above, L1, as another ligand, provides a 6- or 5-coordinated spatial coordination structure for metal M. Such coordination helps the compounds with the structures shown in formulas (4) and (5) to have high chemical stability, thereby helping them to exert efficient and highly selective catalytic effects when used as chiral catalysts of the present invention.

[0064] According to a particularly preferred embodiment of the present invention, the chiral diamine metal catalyst is selected from one or more compounds of the following formula:

[0065]

[0066]

[0067] Where X is independently selected from Cl - BF4 - PF6 - SbF6 - One or more of the following: di(trifluoromethanesulfonyl)imide anion, trifluoromethanesulfonic acid anion, tetrakis(3,5-di(trifluoromethyl)phenyl)boron anion, diphenyl phosphate anion, 2,2'-biphenyl phosphate anion, (R)-2,2'-bidinaphthyl phosphate anion, and (S)-2,2'-bidinaphthyl phosphate anion.

[0068] According to the present invention, in the above-described particularly preferred embodiments, Cl is defined - a) Trifluoromethanesulfonic acid anion; b) BF4 - c, PF6 - For d, SbF6 - If e is the bis(trifluoromethanesulfonyl)imide anion, f is the tetrakis(3,5-bis(trifluoromethyl)phenyl)boron anion, g is the diphenyl phosphate anion, h is the 2,2'-biphenyl phosphate anion, i is the (R)-2,2'-bidinaphthyl phosphate anion, and j is the (R)-2,2'-bidinaphthyl phosphate anion, then the chiral diamine metal catalyst of the above-mentioned particularly preferred embodiment can be obtained by selecting one or more of the following compounds:

[0069] (R,R)-1a、(R,R)-1b、(R,R)-1c、(R,R)-1d、(R,R)-1e、(R,R)-1f、(R,R)-1g、(R,R)-1h、(R,R)-1i、(R,R)-1j、(R,R)-2a、(R,R)-2b、(R,R)-2c、(R,R)-2d、(R,R)-2e、(R,R)-2f、(R,R)-2g、(R,R)-2h、(R,R)-2i、(R,R)-2j、(R,R)-3a、(R,R)-3b、(R,R)-3c、(R,R)-3d、(R,R)-3e、(R,R)-3f、(R,R)-3g、(R,R)-3h、(R,R)-3i、(R,R)-3j、(R,R)-4a、(R,R)-4b、(R,R)-4c、(R,R)-4d、(R,R)-4e、(R,R)-4f、(R,R)-4g、(R,R)-4h、(R,R)-4i、(R,R)-4j、(R,R)-5a、(R,R)-5b、(R,R)-5c、(R,R)-5d、(R,R)-5e、(R,R)-5f、(R,R)-5g、(R,R)-5h、(R,R)-5i、(R,R)-5j、(R,R)-6a、(R,R)-6b、(R,R)-6c、(R,R)-6d、(R,R)-6e、(R,R)-6f、(R,R)-6g、(R,R)-6h、(R,R)-6i、(R,R)-6j、(R,R)-7a、(R,R)-7b、(R,R)-7c、(R,R)-7d、(R,R)-7e、(R,R)-7f、(R,R)-7g、(R,R)-7h、(R,R)-7i、(R,R)-7j、(R,R)-8a、(R,R)-8b、(R,R)-8c、(R,R)-8d、(R,R)-8e、(R,R)-8f、(R,R)-8g、(R,R)-8h、(R,R)-8i、(R,R)-8j、(R,R)-9a、(R,R)-9b、(R,R)-9c、(R,R)-9d、(R,R)-9e、(R,R)-9f、(R,R)-9g、(R,R)-9h、(R,R)-9i、(R,R)-9j、(R,R)-10a、(R,R)-10b、(R,R)-10c、(R,R)-10d、(R,R)-10e、(R,R)-10f、(R,R)-10g、(R,R)-10h、(R,R)-10i、(R,R)-10j、(R,R)-11a、(R,R)-11b、(R,R)-11c、(R,R)-11d、(R,R)-11e、(R,R)-11f、(R,R)-11g、(R,R)-11h、(R,R)-11i、(R,R)-11j、(R,R)-12a、(R,R)-12b、(R,R)-12c、(R,R)-12d、(R,R)-12e、(R,R)-12f、(R,R)-12g、(R,R)-12h、(R,R)-12i、(R,R)-12j、(R,R)-13a、(R,R)-13b、(R,R)-13c、(R,R)-13d、(R,R)-13e、(R,R)-13f、(R,R)-13g、(R,R)-13h、(R,R)-13i、(R,R)-13j、(R,R)-14a、(R,R)-14b、(R,R)-14c、(R,R)-14d、(R,R)-14e、(R,R)-14f、(R,R)-14g、(R,R)-14h、(R,R)-14i、(R,R)-14j、(R,R)-15a、(R,R)-15b、(R,R)-15c、(R,R)-15d、(R,R)-15e、(R,R)-15f、(R,R)-15g、(R,R)-15h、(R,R)-15i、(R,R)-15j、(R,R)-16a、(R,R)-16b、(R,R)-16c、(R,R)-16d、(R,R)-16e、(R,R)-16f、(R,R)-16g、(R,R)-16h、(R,R)-16i、(R,R)-16j、(R,R)-17a、(R,R)-17b、(R,R)-17c、(R,R)-17d、(R,R)-17e、(R,R)-17f、(R,R)-17g、(R,R)-17h、(R,R)-17i、(R,R)-17j、(R,R)-18a、(R,R)-18b、(R,R)-18c、(R,R)-18d、(R,R)-18e、(R,R)-18f、(R,R)-18g、(R,R)-18h、(R,R)-18i、(R,R)-18j、(R,R)-19a、(R,R)-19b、(R,R)-19c、(R,R)-19d、(R,R)-19e、(R,R)-19f、(R,R)-19g、(R,R)-19h、(R,R)-19i、(R,R)-19j、20a、20b、20c、20d、20e、20f、20g、20h、20i、20j、(S,S)-1a、(S,S)-1b、(S,S)-1c、(S,S)-1d、(S,S)-1e、(S,S)-1f、(S,S)-1g、(S,S)-1h、(S,S)-1i、(S,S)-1j、(S,S)-2a、(S,S)-2b、(S,R)-2c、(S,S)-2d、(S,S)-2e、(S,S)-2f、(S,S)-2g、(S,S)-2h、(S,S)-2i、(S,S)-2j、(S,S)-3a、(S,S)-3b、(S,S)-3c、(S,S)-3d、(S,S)-3e、(S,S)-3f、(S,S)-3g、(S,S)-3h、(S,S)-3i、(S,S)-3j、(S,S)-4a、(S,S)-4b、(S,S)-4c、(S,S)-4d、(S,S)-4e、(S,S)-4f、(S,S)-4g、(S,S)-4h、(S,S)-4i、(S,S)-4j、(S,S)-5a、(S,S)-5b、(S,S)-5c、(S,S)-5d、(S,S)-5e、(S,S)-5f、(S,S)-5g、(S,S)-5h、(S,S)-5i、(S,S)-5j、(S,S)-6a、(S,S)-6b、(S,S)-6c、(S,S)-6d、(S,S)-6e、(S,S)-6f、(S,S)-6g、(S,S)-6h、(S,S)-6i、(S,S)-6j、(S,S)-7a、(S,S)-7b、(S,S)-7c、(S,S)-7d、(S,S)-7e、(S,S)-7f、(S,S)-7g、(S,S)-7h、(S,S)-7i、(S,S)-7j、(S,S)-8a、(S,S)-8b、(S,S)-8c、(S,S)-8d、(S,S)-8e、(S,S)-8f、(S,S)-8g、(S,S)-8h、(S,S)-8i、(S,S)-8j、(S,S)-9a、(S,S)-9b、(S,S)-9c、(S,S)-9d、(S,S)-9e、(S,S)-9f、(S,S)-9g、(S,S)-9h、(S,S)-9i、(S,S)-9j、(S,S)-10a、(S,S)-10b、(S,S)-10c、(S,S)-10d、(S,S)-10e、(S,S)-10f、(S,S)-10g、(S,S)-10h、(S,S)-10i、(S,S)-10j、(S,S)-11a、(S,S)-11b、(S,S)-11c、(S,S)-11d、(S,S)-11e、(S,S)-11f、(S,S)-11g、(S,S)-11h、(S,S)-11i、(S,S)-11j、(S,S)-12a、(S,S)-12b、(S,S)-12c、(S,S)-12d、(S,S)-12e、(S,S)-12f、(S,S)-12g、(S,S)-12h、(S,S)-12i、(S,S)-12j、(S,S)-13a、(S,S)-13b、(S,S)-13c, (S,S)-13d, (S,S)-13e, (S,S)-13f, (S,S)-13g, (S,S)-13h, (S,S)-13i, (S,S)-13j, (S,S)-1 4a, (S,S)-14b, (S,S)-14c, (S,S)-14d, (S,S)-14e, (S,S)-14f, (S,S)-14g, (S,S)-14h, (S,S)-14i, (S ,S)-14j, (S,S)-15a, (S,S)-15b, (S,S)-15c, (S,S)-15d, (S,S)-15e, (S,S)-15f, (S,S)-15g, (S,S)- 15h, (S,S)-15i, (S,S)-15j, (S,S)-16a, (S,S)-16b, (S,S)-16c, (S,S)-16d, (S,S)-16e, (S,S)-16f, ( S,S)-16g, (S,S)-16h, (S,S)-16i, (S,S)-16j, (S,S)-17a, (S,S)-17b, (S,S)-17c, (S,S)-17d, (S,S) -17e, (S,S)-17f, (S,S)-17g, (S,S)-17h, (S,S)-17i, (S,S)-17j, (S,S)-18a, (S,S)-18b, (S,S)-18c, (S,S)-18d, (S,S)-18e, (S,S)-18f, (S,S)-18g, (S,S)-18h, (S,S)-18i, (S,S)-18j, (S,S)-19a, (S,S) -19b, (S,S)-19c, (S,S)-19d, (S,S)-19e, (S,S)-19f, (S,S)-19g, (S,S)-19h, (S,S)-19i, (S,S)-19j. ,

[0070] The above compound formulas are illustrated by example; for instance, (R,R)-4a refers to a structure having the above (R,R)-4 and where X is Cl. - The compound; (S,S)-17h refers to a compound having the above-mentioned (S,S)-17 structure and wherein X is a diphenyl phosphate anion.

[0071] According to the present invention, in order to improve the reduction conversion rate of the compound shown in formula (1), preferably, in the compound shown in the above simplified formula, X is selected from a, b, c, d, f, and g. In order to simultaneously improve the chemoselectivity and enantioselectivity of the compound with the structure shown in formula (1), more preferably, X is a. In the reaction for preparing 1-tetrahydronaphthol derivative from 1-naphthol derivative, the chiral diamine metal catalyst is particularly preferably one or more of (R,R)-10a, (S,S)-10a, (R,R)-13a, (S,S)-13a, (R,R)-14a, (S,S)-14a, and 20a; in the reaction for preparing 1-tetrahydronaphthol derivative from 1-naphthol derivative, the chiral diamine metal catalyst is particularly preferably (R,R)-14a and / or (S,S)-14a.

[0072] According to the present invention, preferably, the amount of the chiral diamine metal catalyst is 0.0005-0.3 mmol, more preferably 0.002-0.1 mmol, relative to 1 mmol of the 1-naphthol derivative, for example, it can be 0.005 mmol, 0.02 mmol, 0.05 mmol, 0.08 mmol and 0.1 mmol and any range thereof.

[0073] According to the present invention, the chiral diamine metal catalyst can be prepared by methods disclosed in the art (e.g., patents such as CN105111208A and CN103080118B, as well as some journal articles), and the present invention does not have any particular limitation in this regard.

[0074] According to the present invention, for the smooth progress of the transfer hydrogenation reaction of the 1-naphthol derivative, preferably, the hydrogen source is selected from one or more of sodium formate, lithium formate, potassium formate, cesium formate, formic acid, isopropanol, a mixture of formic acid and sodium formate, and a mixture of formic acid and triethylamine, and more preferably from one or more of sodium formate, cesium formate, and a mixture of formic acid and sodium formate. Wherein, when the hydrogen source is a mixture of formic acid and sodium formate, the mass ratio of formic acid to sodium formate is 1:2-8, preferably 1:4-6, for example, it can be 1:4, 1:5, 1:5.5, and 1:6, or any range thereof. When the hydrogen source is a mixture of formic acid and triethylamine, the mass ratio of formic acid to triethylamine is 1:0.2-0.6, preferably 1:0.3-0.5, for example, it can be 1:0.3, 1:0.4, 1:0.45, and 1:0.5, or any range thereof.

[0075] According to the present invention, in order to obtain better hydrogenation treatment effect and higher yield, the amount of hydrogen source can be adjusted. Preferably, the amount of hydrogen source relative to 1 mmol of the 1-naphthol derivative is 2-50 mmol, preferably 5-30 mmol, for example, it can be 5 mmol, 10 mmol, 15 mmol, 20 mmol and 30 mmol and any value between them.

[0076] According to the present invention, in order to form a better homogeneous catalytic system and provide a better chemical environment for hydrogenation, preferably, the solvent for hydrogenation is selected from one or more of hexafluoroisopropanol, trifluoroethanol, water, [BMIM]PF6, dichloromethane, 1,2-dichloroethane, chloroform, ethyl acetate, tetrahydrofuran, benzene, toluene, xylene, chlorobenzene, diethyl ether, dioxane, acetone, and C1-C10 monohydric alcohols, preferably one or more of hexafluoroisopropanol, trifluoroethanol, and water.

[0077] According to the present invention, the amount of solvent used for hydrogenation treatment can be selected within a wide range. In order to obtain better reaction effect, preferably, the amount of solvent used for hydrogenation treatment is 1-20 mL, more preferably 4-10 mL, relative to 1 mmol of the 1-naphthol derivative. For example, it can be 4 mL, 6 mL, 8 mL and 10 mL and any value between them.

[0078] According to the present invention, in order to reduce the generation of by-products and accelerate the reaction efficiency, the conditions of hydrogenation treatment can be adjusted. Preferably, the conditions of hydrogenation treatment include: temperature -10°C to 130°C, and time 8-60h; more preferably, the conditions of hydrogenation treatment include: temperature 60-90°C (for example, values ​​such as 60°C, 70°C, 80°C, and 90°C, and any range thereof), and time 24-48h (for example, values ​​such as 24h, 32h, 40h, and 48h, and any range thereof).

[0079] According to the present invention, preferably, the hydrogenation process is carried out in a non-reactive gas atmosphere. The non-reactive gas may be, for example, nitrogen and / or argon.

[0080] The second aspect of the present invention provides a method for preparing a chiral 1-tetrahydronaphthol derivative from a 1-naphthol derivative. The method includes hydrogenating the 1-naphthol derivative with a hydrogen source in the presence of a chiral diamine metal catalyst, and adding a reducing solvent to carry out a chiral reduction reaction to obtain a chiral 1-tetrahydronaphthol derivative. The 1-naphthol derivative is a compound of formula (1), and the chiral 1-tetrahydronaphthol derivative is a compound of formula (3).

[0081] Equation (1) Equation (3)

[0082] The chiral diamine metal catalyst, the hydrogen source, the hydrogenation treatment, and the compound of formula (1) are as defined in the method of the first aspect above.

[0083] According to the present invention, in order to facilitate the chiral reduction reaction, the reducing solvent is preferably selected from one or more of methanol, ethanol, isopropanol, dichloromethane, toluene, 1,4-dioxane and tetrahydrofuran, and more preferably from one or more of methanol, ethanol and isopropanol.

[0084] According to the present invention, in order to obtain higher selectivity of chiral alcohol products, preferably, the amount of reducing solvent used is 5-50 mL relative to 1 mmol of the 1-naphthol derivative, preferably 10-30 mL, for example, values ​​such as 10 mL, 15 mL, 20 mL and 30 mL and any range between these values.

[0085] According to the present invention, in order to achieve better results in the chiral reduction reaction, the conditions of the chiral reduction reaction can be adjusted. Preferably, the conditions of the chiral reduction reaction include: a temperature of -10°C to 130°C and a time of 8-60 hours. More preferably, the conditions of the chiral reduction reaction include: a temperature of 60-90°C (e.g., values ​​such as 60°C, 70°C, 80°C, and 90°C, or any range thereof) and a time of 24-48 hours (e.g., values ​​such as 24 hours, 32 hours, 40 hours, and 48 hours, or any range thereof).

[0086] According to the present invention, preferably, the chiral reduction reaction is carried out in a non-reactive gas atmosphere. The non-reactive gas may be, for example, nitrogen and / or argon.

[0087] According to a preferred embodiment of the present invention, the chiral 1-tetrahydronaphthol derivative is selected from one or more compounds of the following formula:

[0088]

[0089]

[0090] According to a particularly preferred embodiment of the present invention, in the method for preparing a chiral 1-tetrahydronaphthol derivative from a 1-naphthol derivative, the 1-naphthol derivative is selected from one or more compounds shown in formulas (1-1), (1-2), (1-3), (1-4), (1-6), (1-7), (1-12), (1-13), and (1-20). Accordingly, the chiral 1-tetrahydronaphthol derivative is selected from one or more compounds shown in formulas (3-1), (3-2), (3-3), (3-4), (3-6), (3-7), (3-12), (3-13), (3-20), (3-24), (3-25), (3-26), (3-27), (3-29), (3-30), (3-35), (3-36), and (3-43).

[0091] This invention achieves the reduction of 1-naphthol derivatives to 1-tetrahydronaphthone derivatives by providing a specific hydrogen source and using a chiral diamine metal catalyst for transfer hydrogenation. Based on this reaction, by simply adding a reducing solvent to change the solvent composition, a further chiral reduction reaction can occur under the same catalyst, enantioselectively preparing chiral 1-tetrahydronaphthol derivatives. The method of this invention effectively protects the substituents, achieving yields of 1-tetrahydronaphthone derivatives exceeding 90%, and yields of 1-tetrahydronaphthol derivatives exceeding 80%, with enantiomeric excess values ​​exceeding 90%. The technical solution of this invention fills a gap in the prior art and is applicable to a wide range of substrates, is simple and easy to operate, operates under mild conditions, is highly efficient, and possesses excellent chemoselectivity and enantioselectivity.

[0092] The present invention will be described in detail below through embodiments.

[0093] In the following examples:

[0094] The conversion rate of the reaction = [converted reactants] / ([converted reactants] + [unconverted reactants]) × 100%. The conversion rate of the transfer hydrogenation reaction of the compound represented by formula (1) of this invention is the separation yield after column purification of the mixture after the reaction.

[0095] Selectivity of reaction products = [target product] / [total products] × 100%.

[0096] For hydrogenated products with two chiral centers, trans / cis refers to the ratio of diastereomers in the reaction product, calculated as [(S,S)+(R,R)] / [(S,R)+(R,S)]. For products with more trans, the enantiomer excess (the absolute value of ee, representing the excess of one enantiomer over another in the reaction product, usually expressed as a percentage) is calculated as: ee = [(S,S)-(R,R)] / [(S,S)+(R,R)]) × 100%. For products with more cis, the enantiomer excess (the absolute value of ee) is calculated as: ee = [(S,R)-(R,S)] / [(S,R)+(R,S)] × 100%.

[0097] The chiral diamine metal catalysts were all prepared according to the preparation methods disclosed in CN105111208A and CN103080118B.

[0098] The compounds shown in formulas (1-1) to (1-24) were all purchased from Shanghai Bid Pharmaceutical Technology Co., Ltd.

[0099] Examples 1-8

[0100] This embodiment illustrates the catalytic effects of different chiral diamine metal catalysts in the preparation of 1-tetrahydronaphthone derivatives from 1-naphthol derivatives. The substrate used is the compound shown in formula (1-1) (i.e., 1-naphthol), and the target product is the compound shown in formula (2-1) (i.e., 1-tetrahydronaphthone).

[0101] The specific steps are as follows: Under a nitrogen atmosphere, 0.1 mmol of the compound shown in formula (1-1), a chiral diamine metal catalyst, 0.5 mmol of sodium formate, and 0.5 mL of hexafluoroisopropanol were added to the reactor, and the mixture was refluxed at 90 °C for 24 h. After cooling the reaction solution to room temperature, it was concentrated under vacuum and purified by silica gel column chromatography to obtain the compound shown in formula (2-1). The conversion rates and selectivity for the product 1-tetrahydronaphthone calculated in Examples 1-8 are shown in Table 1.

[0102] Table 1

[0103]

[0104] Note: The unit x mol% for the amount of chiral diamine metal catalyst refers to the percentage of the molar amount of chiral diamine metal catalyst compared to the molar amount of the compound shown in formula (1-1).

[0105] Examples 9-11

[0106] This embodiment illustrates the effects of using different solvents in the preparation of 1-tetrahydronaphthone derivatives from 1-naphthol derivatives. The substrate used is the compound shown in formula (1-1) (i.e., 1-naphthol), and the target product is the compound shown in formula (2-1) (i.e., 1-tetrahydronaphthone).

[0107] The specific steps are as follows: Under a nitrogen atmosphere, 0.1 mmol of the compound shown in formula (1-1), 0.005 mmol of the chiral diamine metal catalyst (R,R)-14a, 0.5 mmol of sodium formate, and 0.5 mL of solvent were added to the reactor, and the mixture was refluxed at 90 °C for 24 h. After cooling the reaction solution to room temperature, it was concentrated under vacuum and purified by silica gel column chromatography to obtain the compound shown in formula (2-1). The conversion rates and selectivity for the product 1-tetrahydronaphthone calculated in Examples 9-11 are shown in Table 2.

[0108] Table 2

[0109] Example solvent Conversion rate (%) Selectivity (%) 9 water 43 27 10 Trifluoroethanol 25 65 11 Hexafluoroisopropanol ＞99 95

[0110] Examples 12-17

[0111] This embodiment illustrates the effects of using different hydrogen sources in the preparation of 1-tetrahydronaphthone derivatives from 1-naphthol derivatives. The substrate used is the compound shown in formula (1-1) (i.e., 1-naphthol), and the target product is the compound shown in formula (2-1) (i.e., 1-tetrahydronaphthone).

[0112] The specific steps are as follows: Under a nitrogen atmosphere, 0.1 mmol of the compound shown in formula (1-1), 0.005 mmol of the chiral diamine metal catalyst (R,R)-14a, 0.5 mmol of hydrogen source, and 0.5 mL of hexafluoroisopropanol were added to the reactor, and the mixture was refluxed at 90 °C for 24 h. After cooling the reaction solution to room temperature, it was concentrated under vacuum and purified by silica gel column chromatography to obtain the compound shown in formula (2-1). The conversion rates and selectivity for the product 1-tetrahydronaphthone calculated in Examples 12-17 are shown in Table 3.

[0113] Table 3

[0114] Example hydrogen source Conversion rate (%) Selectivity (%) 12 Lithium formate 2 46 13 Sodium formate ＞99 95 14 Potassium formate 46 88 15 Cesium formate 92 76 16 Formic acid: Sodium formate 1:5 ＞99 91 17 Formic acid: Triethylamine 5:2 38 37

[0115] Examples 18-25

[0116] This embodiment illustrates the effect of using different amounts of the same hydrogen source in the reaction of preparing 1-tetrahydronaphthone derivatives from 1-naphthol derivatives. The substrate used is the compound shown in formula (1-1) (i.e., 1-naphthol), and the target product is the compound shown in formula (2-1) (i.e., 1-tetrahydronaphthone).

[0117] The specific steps are as follows: Under a nitrogen atmosphere, 0.1 mmol of the compound shown in formula (1-1), 0.005 mmol of the chiral diamine metal catalyst (R,R)-14a, sodium formate, and 0.5 mL of hexafluoroisopropanol were added to the reactor, and the mixture was refluxed at 90 °C for 24 h. After cooling the reaction solution to room temperature, it was concentrated under vacuum and purified by silica gel column chromatography to obtain the compound shown in formula (2-1). The conversion rates and selectivity for the product 1-tetrahydronaphthone calculated in Examples 18-25 are shown in Table 4.

[0118] Table 4

[0119] Example Sodium formate / mmol Conversion rate (%) Selectivity (%) 18 0.05 3 100 19 0.1 12 94 20 0.2 43 95 21 0.3 60 95 22 0.4 75 94 23 0.5 ＞99 95 24 1 ＞99 80 25 2 ＞99 82

[0120] Examples 26-30

[0121] This embodiment illustrates the effect of different reaction temperatures in the preparation of 1-tetrahydronaphthone derivatives from 1-naphthol derivatives. The substrate used is the compound shown in formula (1-1) (i.e., 1-naphthol), and the target product is the compound shown in formula (2-1) (i.e., 1-tetrahydronaphthone).

[0122] The specific steps are as follows: Under a nitrogen atmosphere, 0.1 mmol of the compound shown in formula (1-1), 0.005 mmol of the chiral diamine metal catalyst (R,R)-14a, 0.5 mmol of sodium formate, and 0.5 mL of hexafluoroisopropanol were added to the reactor, and the reaction was carried out at a certain temperature for 24 h. After cooling the reaction solution to room temperature, it was concentrated under vacuum and purified by silica gel column chromatography to obtain the compound shown in formula (2-1). The conversion rates and selectivity for the product 1-tetrahydronaphthone calculated in Examples 26-30 are shown in Table 5.

[0123] Table 5

[0124] Example Reaction temperature (°C) Conversion rate (%) Selectivity (%) 26 50 32 88 27 60 73 81 28 70 93 83 29 80 ＞99 86 30 90 ＞99 95

[0125] Examples 31-37

[0126] This embodiment illustrates the effects of different reducing solvents in the preparation of chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives. The substrate used is the compound shown in formula (1-1) (i.e., 1-naphthol), and the target product is the compound shown in formula (3-1) (i.e., chiral 1-tetrahydronaphthol).

[0127] The specific steps are as follows: Under a nitrogen atmosphere, 0.1 mmol of the compound shown in formula (1-1), 0.01 mmol of the chiral diamine metal catalyst (R,R)-14a, 0.5 mmol of sodium formate, and 0.5 mL of hexafluoroisopropanol were added to the reactor, and the mixture was refluxed at 90 °C for 24 h. After the reaction solution cooled to room temperature, 1.5 mL of reducing solvent was added to the reactor, and the mixture was refluxed at 90 °C for 24 h under a nitrogen atmosphere. The reaction solution was filtered and concentrated under vacuum, and then purified by silica gel column chromatography to obtain the compound shown in formula (3-1). Then, the enantiomeric excess value (i.e., ee value) of the compound shown in formula (3-1) was analyzed by high performance liquid chromatography (HPLC) using a chiral column. The conversion rates calculated in Examples 31-37 and the chemoselectivity and enantioselectivity of the product chiral 1-tetrahydronaphthol are shown in Table 6.

[0128] Table 6

[0129] Example Reducing solvent Conversion rate (%) Chemical selectivity (%) Enantiomer selectivity / (ee, %) 31 methanol ＞99 90 92 32 Isopropanol ＞99 63 87 33 ethanol ＞99 5 72 34 dichloromethane ＞99 2 3 35 Toluene ＞99 3 2 36 1,4-Dioxane ＞99 4 2 37 Tetrahydrofuran ＞99 3 2

[0130] Examples 38-41

[0131] This embodiment illustrates the effect of different reaction temperatures in the preparation of chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives. The substrate used is the compound shown in formula (1-1) (i.e., 1-naphthol), and the target product is the compound shown in formula (3-1) (i.e., chiral 1-tetrahydronaphthol).

[0132] The specific steps are as follows: Under a nitrogen atmosphere, 0.1 mmol of the compound shown in formula (1-1), 0.01 mmol of the chiral diamine metal catalyst (R,R)-14a, 0.5 mmol of sodium formate, and 0.5 mL of hexafluoroisopropanol were added to the reactor, and the mixture was refluxed at 90 °C for 24 h. After the reaction solution cooled to room temperature, 1.5 mL of methanol was added to the reactor, and the mixture was reacted at a certain temperature under a nitrogen atmosphere for 24 h. The reaction solution was filtered and concentrated under vacuum, and then purified by silica gel column chromatography to obtain the compound shown in formula (3-1). Then, the enantiomeric excess value (i.e., ee value) of the compound shown in formula (3-1) was analyzed by high performance liquid chromatography (HPLC) using a chiral column. The conversion rates calculated in Examples 38-41 and the chemoselectivity and enantioselectivity of the product chiral 1-tetrahydronaphthol are shown in Table 7.

[0133] Table 7

[0134] Example reaction temperature Conversion rate (%) Chemical selectivity (%) Enantiomer selectivity / (ee, %) 38 25 ＞99 6 30 39 50 ＞99 64 92 40 60 ＞99 88 92 41 90 ＞99 90 92

[0135] Examples 42-65

[0136] This example illustrates the reaction effects of using different substrates in the preparation of 1-tetrahydronaphthone derivatives from 1-naphthol derivatives.

[0137] The specific steps are as follows: Under a nitrogen atmosphere, 0.1 mmol of the compound shown in formula (1), 0.01 mmol of the chiral diamine metal catalyst (R,R)-14a, 0.5 mmol of sodium formate, and 0.5 mL of hexafluoroisopropanol were added to the reactor, and the mixture was refluxed at 90 °C for 24 h. After cooling the reaction solution to room temperature, it was concentrated under vacuum and purified by silica gel column chromatography to obtain the compound shown in formula (2). The yields calculated in Examples 42-65 are shown in Table 8.

[0138] Table 8

[0139]

[0140]

[0141] Examples 66-83

[0142] This example illustrates the reaction effects of using different substrates in the preparation of chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives.

[0143] The specific steps are as follows: Under a nitrogen atmosphere, 0.1 mmol of the compound shown in formula (1), 0.01 mmol of the chiral diamine metal catalyst (R,R)-14a, 0.5 mmol of sodium formate, and 0.5 mL of hexafluoroisopropanol were added to the reactor, and the mixture was refluxed at 90 °C for 24 h. After the reaction solution cooled to room temperature, 1.5 mL of methanol was added to the reactor, and the mixture was refluxed at 90 °C for 24 h under a nitrogen atmosphere. The reaction solution was filtered and concentrated under vacuum, and then purified by silica gel column chromatography to obtain the compound shown in formula (3). Then, the enantiomeric excess value (i.e., ee value) of the compound shown in formula (3) was analyzed by high performance liquid chromatography (HPLC) using a chiral column. The yields calculated in Examples 66-83 and the enantiomeric excess values ​​(i.e., ee values) of the chiral 1-tetrahydronaphthol derivatives are shown in Table 9.

[0144] Table 9

[0145] Example Substrate product Yield (%) Product ee value (%) 66 The compound shown in formula (1-1) The compound shown in formula (3-1) 92 94 67 The compound shown in formula (1-2) The compound shown in formula (3-2) 80 96 68 The compounds shown in formula (1-3) The compound shown in formula (3-3) 83 96 69 The compounds shown in formula (1-4) The compounds shown in formula (3-4) 85 94 70 The compounds shown in formula (1-5) The compounds shown in formula (3-5) 70 92 71 The compounds shown in formula (1-6) The compounds shown in formula (3-6) 86 94 72 The compounds shown in formula (1-7) The compounds shown in formula (3-7) 86 93 73 The compounds shown in formula (1-9) The compounds shown in formula (3-9) 65 92 74 The compounds shown in formula (1-10) The compound shown in formula (3-10) 62 90 75 The compound shown in formula (1-12) The compound shown in formula (3-12) 88 96 76 The compound shown in formula (1-13) The compound shown in formula (3-13) 88 92 77 The compound shown in formula (1-14) The compound shown in formula (3-14) 75 96 78 The compound shown in formula (1-15) The compound shown in formula (3-15) 64 96 79 The compound shown in formula (1-19) The compound shown in formula (3-19) 70 90 80 The compound shown in formula (1-20) The compound shown in formula (3-20) 89 90 81 The compound shown in formula (1-21) The compound shown in formula (3-21) 40 85 82 The compound shown in formula (1-22) The compound shown in formula (3-22) 69 90 83 The compound shown in formula (1-23) The compound shown in formula (3-23) 67 96

[0146] To intuitively illustrate the properties and characterization process of the 1-tetrahydronaphthone derivative and the chiral 1-tetrahydronaphthol derivative prepared from the 1-naphthol derivative using the method of the present invention, the present invention provides, exemplarily, the identification results of the 1-tetrahydronaphthone derivative and the chiral 1-tetrahydronaphthol derivative prepared in Examples 42-83, as shown in Table 10.

[0147] Table 10

[0148]

[0149]

[0150]

[0151]

[0152]

[0153]

[0154] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for preparing 1-tetrahydronaphthone derivatives from 1-naphthol derivatives, characterized in that, The method includes hydrogenating a 1-naphthol derivative with a hydrogen source in the presence of a chiral diamine metal catalyst to obtain a 1-tetrahydronaphthone derivative, wherein the 1-naphthol derivative is the compound shown in formula (1) and the 1-tetrahydronaphthone derivative is the compound shown in formula (2). Equation (1) Equation (2) Wherein, A is a benzene ring or a naphthalene ring, and R1 is selected from one or more of H, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C1-C12 alkoxy, substituted or unsubstituted C3-C12 cycloalkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-C12 acyl, substituted or unsubstituted C2-C12 ester, substituted or unsubstituted amino, halogen, and hydroxyl, wherein the substituted C1-C12 alkyl, substituted C1-C12... The substituents of the alkoxy group, the substituted C3-C12 cycloalkyl group, the substituted C6-C20 aryl group, the substituted C1-C12 acyl group, the substituted C2-C12 ester group, and the substituted amino group are each independently selected from one or more of the following: C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C6-C14 aryl, C1-C6 acyl, C2-C6 ester, amino, halogen, and hydroxyl; R2 is selected from one or more of H and C1-C12 alkyl.

2. The method according to claim 1, wherein, A is a benzene ring or a naphthyl ring, and R1 is selected from one or more of H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C6-C14 aryl, substituted or unsubstituted C1-C6 acyl, substituted or unsubstituted C2-C6 ester, substituted or unsubstituted amino, halogen, and hydroxyl, wherein the substituted C1-C6 alkyl, substituted C1-C6 alkoxy... The substituents of the group, including the substituted C3-C6 cycloalkyl, the substituted C6-C14 aryl, the substituted C1-C6 acyl, the substituted C2-C6 ester, and the substituted amino, are each independently selected from one or more of the following: C1-C3 alkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, C6-C14 aryl, C1-C3 acyl, C2-C3 ester, amino, halogen, and hydroxyl; R2 is selected from one or more of H and C1-C6 alkyl. Preferably, A is a benzene ring or a naphthalene ring, and R1 is selected from one or more of H, substituted or unsubstituted C1-C3 alkyl groups, substituted or unsubstituted C1-C3 alkoxy groups, substituted or unsubstituted C3-C6 cycloalkyl groups, substituted or unsubstituted C6-C14 aryl groups, substituted or unsubstituted C1-C3 acyl groups, substituted or unsubstituted C2-C3 ester groups, substituted or unsubstituted amino groups, halogens, and hydroxyl groups, wherein the substituted C1-C3 alkyl groups, substituted C1-C3 alkoxy groups, substituted C2-C3 alkoxy groups, substituted C3-C6 cycloalkyl groups, substituted C6-C14 aryl groups, substituted C6-C14 aryl groups, substituted C1-C3 alkoxy groups, substituted C2-C3 alkoxy groups, substituted C2-C3 alkoxy groups, substituted C3-C6 cycloalkyl groups, substituted C6-C14 aryl groups, substituted C6-C14 aryl groups, substituted C1-C14 alkoxy groups, substituted C2-C3 alkoxy groups, substituted C2-C3 alkoxy groups, substituted C3-C14 alkoxy groups, substituted C2 ... The substituents of the alkoxy group, the substituted C3-C6 cycloalkyl group, the substituted C6-C14 aryl group, the substituted C1-C3 acyl group, the substituted C2-C3 ester group, and the substituted amino group are each independently selected from one or more of the following: C1-C3 alkyl group, C1-C3 alkoxy group, C3-C6 cycloalkyl group, C6-C14 aryl group, C1-C3 acyl group, C2-C3 ester group, amino group, halogen, and hydroxyl group; R2 is selected from one or more of H and C1-C3 alkyl group. More preferably, A is a benzene ring or a naphthyl ring, and R1 is selected from one or more of H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, benzyl, formyl, acetyl, propionyl, methyl ester, ethyl ester, amino, F, Cl, Br, hydroxy, aminomethyl, aminoethyl, hydroxymethyl, hydroxyethyl, trifluoromethyl, benzyloxy, formamide, acetamide, propionamide, methyl ester, and ethyl ester; R2 is selected from one or more of H, methyl, ethyl, n-propyl, and isopropyl.

3. The method according to claim 1 or 2, wherein, The 1-naphthol derivative is selected from one or more compounds shown in the following formula:

4. The method according to any one of claims 1-3, wherein, The 1-tetrahydronaphthone derivative is selected from one or more compounds shown in the following formula:

5. The method according to any one of claims 1-4, wherein, The chiral diamine metal catalyst is selected from one or more compounds shown in formula (4) and formula (5): Equation (4) Equation (5) In this context, each metal M is independently selected from one or more of ruthenium, rhodium, and iridium; each L1 is independently selected from substituted or unsubstituted η. 6 -Benzene coordination group and substituted or unsubstituted η 5 - One or more of the cyclohexene coordination groups, and the substituents optionally present in L1 are each independently selected from one or more of the C1-C6 alkyl groups; L2 is selected from C1-C6 oxyalkylene groups, C1-C6 sulfalkylene groups, and One or more of them, wherein R x Selected from one or more alkylene groups of C1-C3, R y Selected from one or more of H, C1-C3 alkoxy groups, and halogens; X is independently selected from Cl. - ,Br - I - CH3COO - NO3 - HSO4 - H2PO4 - BF4 - SbF6 - PF6 - X is selected from one or more of the following: bis(trifluoromethanesulfonyl)imide anion, trifluoromethanesulfonic acid anion, substituted or unsubstituted C24-C32 tetraarylboron anion, substituted or unsubstituted C12-C36 diarylphosphate anion and substituted or unsubstituted C12-C36 biaryldiol-derived phosphate anion, wherein the substituents optionally present in X are each independently selected from one or more of the following: C1-C3 alkyl, C1-C3 alkoxy, C1-C3 amide, halogen, nitro, trifluoromethyl and hydroxyl; Preferably, each of the metals M is independently selected from one or more of ruthenium, rhodium, and iridium; each of the metals L1 is independently selected from η. 6 -Benzene ligand, η 6 -1,4-Dimethylbenzene ligand, η 6 -1-Methyl-4-isopropylphenyl ligand, η 6 -1,3,5,-Trimethylbenzene ligand, η 6 -1,2,3,4,5-pentamethylbenzene ligand, η 6 -1,2,3,4,5,6-Hexamethylbenzene ligand, η 5 -Maocene ligand and eta 5 - One or more of the pentamethylcenyl ligands; L2 is selected from -CH2-O-CH2-CH2-, -CH2-O-CH2-CH2-CH2-CH2-, -CH2-S-CH2-CH2- and One or more of them, wherein R x Selected from methylene or ethylene, R y Selected from one or more of H, methoxy, ethoxy, F, Cl, and Br; X is independently selected from Cl. - BF4 - SbF6 - PF6 - X is selected from one or more of the following: bis(trifluoromethanesulfonyl)imine anion, trifluoromethanesulfonic acid anion, substituted or unsubstituted C24-C32 tetraarylboronic anion, substituted or unsubstituted C12-C36 diarylphosphate anion and substituted or unsubstituted C12-C36 biaryldiol-derived phosphate anion, wherein the substituents optionally present in X are each independently selected from one or more of methyl, ethyl, methoxy, ethoxy, acetamido, F, Cl, Br, nitro, trifluoromethyl and hydroxy. More preferably, each of the metals M is independently selected from one or more of ruthenium, rhodium, and iridium; each of the metals L1 is independently selected from η. 6 -Benzene ligand, η 6 -1-Methyl-4-isopropylphenyl ligand, η 6 -1,2,3,4,5,6-hexamethylbenzene ligand and eta 5 -One or more of the pentamethylcenyl ligands; L2 is selected from... One or more of them; X is independently selected from Cl. - BF4 - PF6 - SbF6 - One or more of the following: di(trifluoromethanesulfonyl)imide anion, trifluoromethanesulfonic acid anion, tetraphenylboron anion, tetra[3,5-di(trifluoromethyl)phenyl]boron anion, diphenyl phosphate anion, di-p-methylphenyl phosphate anion, di(2,4,6-trimethylphenyl) phosphate anion, di-p-methoxyphenyl phosphate anion, di-p-fluoromethylphenyl phosphate anion, di-p-trifluoromethylphenyl phosphate anion, 2,2'-biphenyl phosphate anion, (R)-2,2'-bi-naphthyl phosphate anion, (S)-2,2'-bi-naphthyl phosphate anion, (R)-8H-2,2'-bi-naphthyl phosphate anion, and (S)-8H-2,2'-bi-naphthyl phosphate anion.

6. The method according to claim 5, wherein, Define the ligands in equations (4) and (5) For formula (6), the compound forming the ligand shown in formula (6) is selected from one or more of the compounds shown in the following formulas: Equation (I-1) Equation (I-2) Equation (I-3) Equation (I-4) Equation (I-5) Equation (I-6) Equation (I-7) Equation (I-8) Equation (I-9) Ar1 and Ar2 are each independently selected from one or more of substituted or unsubstituted phenyl groups and substituted or unsubstituted naphthyl groups, and the substituents optionally present in Ar1 and Ar2 are each independently selected from one or more of C1-C3 alkyl groups, C1-C3 alkoxy groups, C1-C3 hydroxyalkyl groups, halogens, hydroxyl groups and carboxyl groups. R is selected from one or more of C1-C8 alkyl, trifluoromethyl, substituted or unsubstituted phenyl and substituted or unsubstituted naphthyl groups, and the substituents optionally present in R are each independently selected from one or more of C1-C8 alkyl, methoxy, F, Cl, Br, nitro and trifluoromethyl groups. R' is independently selected from one or more of C1-C10 alkyl, trifluoromethyl, substituted amino, substituted or unsubstituted phenyl and substituted or unsubstituted naphthyl groups, and the substituents optionally present in R' are independently selected from one or more of C1-C10 alkyl, methoxy, F, Cl, Br, nitro and trifluoromethyl groups. R” is independently selected from one or more of H, substituted or unsubstituted benzyl and C1-C10 alkyl, and the substituents optionally present in R” are independently selected from one or more of C1-C10 alkyl, methoxy, F, Cl, Br, nitro and trifluoromethyl.

7. The method according to claim 5 or 6, wherein, The chiral diamine metal catalyst is selected from one or more compounds shown in the following formula: Where X is independently selected from Cl - BF4 - PF6 - SbF6 - One or more of the following: di(trifluoromethanesulfonyl)imide anion, trifluoromethanesulfonic acid anion, tetrakis(3,5-di(trifluoromethyl)phenyl)boron anion, diphenyl phosphate anion, 2,2'-biphenyl phosphate anion, (R)-2,2'-bidinaphthyl phosphate anion, and (S)-2,2'-bidinaphthyl phosphate anion.

8. The method according to any one of claims 1-7, wherein, The hydrogen source is selected from one or more of sodium formate, lithium formate, potassium formate, cesium formate, formic acid, isopropanol, a mixture of formic acid / sodium formate, and a mixture of formic acid / triethylamine, preferably one or more of sodium formate, cesium formate, and a mixture of formic acid / sodium formate; Preferably, when the hydrogen source is a mixture of formic acid and sodium formate, the mass ratio of formic acid to sodium formate is 1:2-8, more preferably 1:4-6; Preferably, when the hydrogen source is a mixture of formic acid and triethylamine, the mass ratio of formic acid to triethylamine is 1:0.2-0.6, more preferably 1:0.3-0.5; Preferably, the amount of hydrogen source used is 2-50 mmol, more preferably 5-30 mmol, relative to 1 mmol of the 1-naphthol derivative; Preferably, the solvent for the hydrogenation treatment is selected from one or more of hexafluoroisopropanol, trifluoroethanol, water, [BMIM]PF6, dichloromethane, 1,2-dichloroethane, chloroform, ethyl acetate, tetrahydrofuran, benzene, toluene, xylene, chlorobenzene, diethyl ether, dioxane, acetone, and C1-C10 monohydric alcohols, and more preferably one or more of hexafluoroisopropanol, trifluoroethanol, and water; Preferably, the amount of solvent used for the hydrogenation treatment is 1-20 mL, more preferably 4-10 mL, relative to 1 mmol of the 1-naphthol derivative; Preferably, the amount of the chiral diamine metal catalyst is 0.0005-0.3 mmol, more preferably 0.002-0.1 mmol, relative to 1 mmol of the 1-naphthol derivative; Preferably, the hydrogenation treatment conditions include: temperature -10℃ to 130℃, time 8-60h; more preferably, the hydrogenation treatment conditions include: temperature 60-90℃, time 24-48h.

9. A method for preparing chiral 1-tetrahydronaphthol derivatives from 1-naphthol derivatives, characterized in that, The method includes hydrogenating a 1-naphthol derivative with a hydrogen source in the presence of a chiral diamine metal catalyst, and adding a reducing solvent to carry out a chiral reduction reaction to obtain a chiral 1-tetrahydronaphthol derivative, wherein the 1-naphthol derivative is the compound shown in formula (1), and the chiral 1-tetrahydronaphthol derivative is the compound shown in formula (3). Equation (1) Equation (3) The chiral diamine metal catalyst, the hydrogen source, the hydrogenation treatment, and the compound of formula (1) are defined by the method described in any one of claims 1-8.

10. The method according to claim 9, wherein, The reducing solvent is selected from one or more of methanol, ethanol, isopropanol, dichloromethane, toluene, 1,4-dioxane and tetrahydrofuran, preferably one or more of methanol, ethanol and isopropanol; Preferably, the amount of reducing solvent used is 5-50 mL, more preferably 10-30 mL, relative to 1 mmol of the 1-naphthol derivative; Preferably, the conditions for the chiral reduction reaction include: temperature -10℃ to 130℃, time 8-60h; more preferably, the conditions for the chiral reduction reaction include: temperature 60-90℃, time 24-48h.

11. The method according to claim 9 or 10, wherein, The chiral 1-tetrahydronaphthol derivative is selected from one or more compounds shown in the following formula:

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