An electrochemically reduced-promoted metal-catalyzed asymmetric coupling method

Abstract

The application discloses a method for asymmetric coupling. The application provides a preparation method for electrochemical asymmetric coupling, which comprises the following steps: performing electrochemical asymmetric coupling reaction on a compound as shown in formula I and a compound as shown in formula II in the presence of a Co salt, a chiral nitrogen ligand and an electrolyte in a solvent to obtain a compound as shown in formula III or a compound as shown in formula IV. The preparation method has the characteristics of high selectivity, mild reaction condition, environmental friendliness, high yield, good purity, good enantioselectivity and suitability for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to an electrochemical reduction-promoted metal-catalyzed asymmetric coupling method. Background Technology

[0002] The construction of axially chiral biaryl compounds is important because they are fundamental structural units found in ligands, organocatalysts, and natural products. Over the past decade, various methods have been developed to synthesize trans-resistive biaryl compounds, including transition metal-catalyzed enantioselective synthesis via cross-coupling between aryl halides and aryl metal substances, the latter consisting of organomagnesium, organozinc, organoboron, or organindium reagents. Since aryl metal reagents are typically prepared from the corresponding aryl halides, enantioselective reductive coupling of two aryl halides to obtain axially chiral biaryl compounds offers an attractive, step-economical alternative. Although Ni-catalyzed reductive coupling of two aryl halides using Mn, Zn, or Mg powders as reducing agents has been extensively studied, the enantioselective construction of axially chiral biaryl compounds is rare. Therefore, developing a highly enantioselective Ni-catalyzed reductive coupling of aryl halides to form biaryl compounds with a broad substrate range would provide a complementary and alternative approach to traditional cross-coupling and oxidative coupling in biaryl synthesis. The past decade has witnessed a resurgence in electrochemical organic synthesis, driven by the need for more atom-economic reaction platforms to address growing global sustainability concerns and awareness. As part of our ongoing interest in combining cathodic reduction with transition metal catalysis, we have developed the first example of nickel-catalyzed electrochemical enantioselective construction of axially chiral biaryl compounds. Summary of the Invention

[0003] The purpose of this invention is to overcome the shortcomings of existing preparation techniques and provide an electrochemical reduction-promoted metal-catalyzed asymmetric coupling method with high selectivity, mild reaction conditions, environmental friendliness, high yield, and good purity, suitable for industrial production.

[0004] A method for preparing an asymmetric coupling includes the following steps: in a solvent, in the presence of a Co salt, a chiral nitrogen ligand, and an electrolyte, a compound as shown in Formula I and a compound as shown in Formula II are subjected to an electrochemical asymmetric coupling reaction as shown below to obtain a compound as shown in Formula III or a compound as shown in Formula IV.

[0005]

[0006] in:

[0007] Ring A and ring A' are independently C6-C 10 aryl, with one or more R a Replacement C6-C10 aryl, 5-10 heteroaryl or with one or more R b Substituted 5-10-membered heteroaryl groups; when multiple substituents are present, they may be identical or different; the 5-10-membered heteroaryl group may be replaced by one or more R groups. b In the substituted 5-10 membered heteroaryl groups, the heteroatom is selected from N, O or S, and the number of heteroatoms is 1-3.

[0008] R a and R b Independently halogen, C1-C 30 Alkyl, C3-C 30 cycloalkyl, C2-C 30 alkenyl, -O-(C2-C 30 alkenyl), C6-C 30 aryl, C1-C 30 alkoxy groups,

[0009] R a-1 and R a-2 Independently for C1-C 30 Alkyl groups;

[0010] R 1 and R 1 'Independently for R 1-1 and R 1-2 Independently for C1-C 30 Alkyl, C6-C 30 aryl or phenyl-substituted C1-C 30 Alkyl groups;

[0011] R 2 and R 2 'Independently H, C1-C 30 Alkyl, C4-C 30 Cycloalkenyl, C6-C 30 aryl, with one or more R 2-1 Replacement C6-C 30 aryl;

[0012] R 2-1 Independently for C1-C 30 alkyl, C 1- C 30 alkoxy groups, C6-C 30 aryl groups, halogens, and C1-C atoms substituted with one or more halogens 30 alkyl,

[0013] R 2-1-1 or R 2-1-2Independently for C1-C 30 Alkyl groups;

[0014] X and X' are halogens independently;

[0015] The compound shown in Formula I may be the same as or different from the compound shown in Formula II; when they are different, the atomic number of X in the compound shown in Formula I is not less than the atomic number of X' in the compound shown in Formula II.

[0016] In certain preferred embodiments of the present invention, certain groups in the compounds represented by formulas I, II, III and IV are defined as follows, and groups not mentioned are as described in any embodiment of the present invention (hereinafter referred to as "in some embodiments").

[0017] In some implementations, when ring A and ring A' are independently C6-C 10 aryl and one or more R a Replacement C6-C 10 When the aryl group is present, the C6-C 10 aryl and one or more R a Replacement C6-C 10 C6-C in aryl 10 The aryl group can be phenyl or naphthyl, for example, phenyl.

[0018] In some implementations, when ring A and ring A' are independently 5-10 membered heteroaryl groups or are surrounded by one or more R groups... b When the substituted 5-10 heteroaryl group is used, the 5-10 heteroaryl group is pyridyl or thiophene, for example, pyridyl.

[0019] In some implementations, when R a and R b When it is a halogen on its own, the halogen is F, Cl, Br or I.

[0020] In some implementations, when R a and R b Independently for C1-C 30 When alkyl, the C1-C 30 The alkyl group can be C1-C 10 Alkyl groups; for example, C1-C6 alkyl groups, and for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; and for example, methyl, ethyl or n-pentyl.

[0021] In some implementations, when R a and R b Independently for C3-C 30 When cycloalkyl, the C3-C 30The cycloalkyl group can be C3-C 10 Cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; for example, cyclopropyl and cyclohexyl.

[0022] In some implementations, when R a and R b Independently for C2-C 30 When the alkenyl group is present, the C2-C 30 The alkenyl group can be C2-C 10 The alkenyl group; for example, the alkenyl group of C2-C6, and also, for example, vinyl, propenyl, allyl or -CH2-(CH2)2CH=CH2; and also, for example, vinyl.

[0023] In some implementations, when R a and R b Independently -O-(C2-C 30 When the alkenyl group is present, the C2-C 30 The alkenyl group can be C2-C 10 The alkenyl group; for example, a C2-C6 alkenyl group, or vinyl, propenyl, allyl or -CH2-(CH2)2CH=CH2; and for example, -CH2-(CH2)2CH=CH2.

[0024] In some implementations, when R a and R b Independently for C6-C 30 When the aryl group is present, the C6-C 30 The aryl group can be C6-C 10 Aryl groups, such as phenyl or naphthyl.

[0025] In some implementations, when R a and R b Independently for C1-C 30 When the alkoxy group is present, the C1-C 30 The alkoxy group can be C1-C. 10 Alkyl groups; for example, C1-C6 alkoxy groups, and also, for example, methoxy, ethoxy, isopropoxy, tert-butoxy; and also, for example, methoxy.

[0026] In some implementations, when R a-1 and R a-2 Independently for C1-C 30 When alkyl, the C1-C 30 The alkyl group can be C1-C 10 Alkyl groups; for example, C1-C6 alkyl groups, and for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl, and for example, methyl.

[0027] In some implementations, when R 1-1 and R 1-2 Independently for C1-C 30 When alkyl, the C1-C 30 The alkyl group can be C1-C 10 Alkyl groups; for example, C1-C6 alkyl groups, and for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; and for example, methyl.

[0028] In some implementations, when R 1-1 and R 1-2 Independently for C6-C 30 When the aryl group is present, the C6-C 30 The aryl group can be C6-C 10 Aryl groups, such as phenyl or naphthyl.

[0029] In some implementations, when R 1-1 and R 1-2 Independently, C1-C substituted with phenyl 30 When alkyl; the C1-C substituted with phenyl 30 C1-C in alkyl groups 30 The alkyl group can be C1-C 10 Alkyl groups; for example, C1-C6 alkyl groups, and for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; and for example, methyl.

[0030] In some implementations, when R 2 and R 2 'Independently for C1-C 30 When alkyl, the C1-C 30 The alkyl group can be C1-C 10 Alkyl groups; for example, C1-C6 alkyl groups, and for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; and for example, methyl.

[0031] In some implementations, when R 2 and R 2 'Independently for C3-C 30 When the cycloalkenyl group is present, the C1-C 30 The cycloalkenyl group can be C3-C 10 Cycloalkenyl groups; for example, C3-C6 cycloalkenyl groups, and for example... For example,

[0032] In some implementations, when R 2 and R 2 'Independently for C6-C30 aryl or aryl group or one or more R 2-1 Replacement C6-C 30 The aryl group, the C6-C 30 aryl or aryl group or one or more R 2-1 Replacement C6-C 30 C6-C in aryl 30 Aryl groups can be C6-C 10 Aryl groups, such as phenyl or naphthyl.

[0033] In some implementations, when R 2-1 Independently for C1-C 30 Alkyl groups or C1-C atoms substituted with one or more halogens 30 When alkyl, the C1-C 30 Alkyl groups or C1-C atoms substituted with one or more halogens 30 C1-C in alkyl groups 30 The alkyl group can be C1-C 10 Alkyl groups; for example, C1-C6 alkyl groups, and for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; and for example, ethyl, n-propyl, isopropyl or tert-butyl.

[0034] In some implementations, when R 2-1 C 1- C 30 When the alkoxy group is present, the C1-C 30 The alkoxy group can be C1-C. 10 Alkyl groups; for example, C1-C6 alkoxy groups, and also, for example, methoxy, ethoxy, isopropoxy, tert-butoxy; and also, for example, methoxy.

[0035] In some implementations, when R 2-1 For C6-C 30 When the aryl group is present, the C6-C 30 The aryl group can be C6-C 10 Aryl groups, such as phenyl or naphthyl.

[0036] In some implementations, when R 2-1 C1-C is a halogen or is substituted by one or more halogens. 30 When alkyl, the halogen or C1-C substituted with one or more halogens. 30 The halogen in the alkyl group is F, Cl, Br or I.

[0037] In some implementations, when R 2-1 C1-C substituted by one or more halogens 30 When alkyl, the C1-C 30The alkyl group can be a C1-C6 alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; and also, for example, ethyl, n-propyl, isopropyl or tert-butyl.

[0038] In some implementations, when R 2-1 C1-C substituted by one or more halogens 30 When the alkyl group is used, the number of halogens can be 1, 2 or 3; for example, trifluoromethyl.

[0039] In some implementations, when R 2-1-1 or R 2-1-2 Independently for C1-C 30 When alkyl, the C1-C 30 The alkyl group can be C1-C 10 Alkyl groups; for example, C1-C6 alkyl groups, and for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; and for example, methyl.

[0040] In some implementations, when X and X' are independently halogens, the halogen is F, Cl, Br, or I, for example Br or I.

[0041] In some implementations, the one or more R 2-1 Replacement C6-C 30 The aryl group is selected from

[0042] In some embodiments, when the compound shown in Formula I is different from the compound shown in Formula II, X in the compound shown in Formula I is I, and R is R. 1 For -OBn; in the compounds shown in Formula II, X' is Br, R 1’ It is -CO2Ph.

[0043] In some implementations, R a and R b Independently, it can be H, F, methyl, ethyl, n-pentyl, cyclopropyl, cyclohexyl, methoxy, vinyl, phenyl, -COOCH3, -OCH2(CH2)2CH=CH2,

[0044] In some implementations, ring A and ring A' are independently...

[0045] In some implementations, R 1 and R 1 'Independently -OBn or -CO2Ph.'

[0046] In some implementations, R 2 and R 2 'Independently H, methyl, phenyl, naphthyl,

[0047] In some embodiments, in the compound represented by Formula I, R 2 Located at the para or meta position of X; in the chemical shown in Formula II, R 2 'Located opposite or between X'.

[0048] In some embodiments, the compounds shown in Formula I and Formula II are independently...

[0049]

[0050]

[0051] In some embodiments, the compound represented by Formula III is

[0052]

[0053] Or its enantiomers.

[0054] In some embodiments, when the compound represented by Formula I is not the same as the compound represented by Formula II, the compound represented by Formula I, the compound represented by Formula II, and the corresponding compound represented by Formula III are any one of the following groups: Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers, Or its enantiomers.

[0055] In some embodiments, the chiral nitrogen ligand is a compound of formula IV or its enantiomer.

[0056]

[0057] Among them, R 4 and R 5 Independent of H, C1-C 10 Alkyl, C3-C 15 cycloalkyl, C6-C 10 Aryl or phenyl-substituted C1-C 10 alkyl;

[0058] Or, R 4 and R 5 Formed together with the attached carbon: Where n is 0-6, for example 1 or 2;

[0059] R 6 and R 7 Independently H, phenyl, or naphthyl, and R 6 and R 7 Not both H;

[0060] Or, R 6 and R 7 Formed together with the attached carbon:

[0061] In some implementations, when R 4 and R 5 For C1-C 10 When alkyl, the C1-C 10 The alkyl group can be C1-C6 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl or -CH(CH2CH3)2; or, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl or -CH(CH2CH3)2.

[0062] In some implementations, when R 4 Or R 5 For C3-C 15 In the case of cycloalkyl groups, the C3-C 15 Cycloalkyl groups can be C3-C 12 cycloalkyl groups, such as cyclopropyl, cyclopentyl, cyclohexyl, and cyclooctyl.

[0063] In some implementations, when R 4 Or R 5 For C6-C 10 In the aryl case, the C6-C 10 The aryl group is either phenyl or naphthyl.

[0064] In some implementations, when R 4 or R 5 C1-C substituted with phenyl 10 When alkyl; the C1-C 10 The alkyl group can be C1-C6 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl or -CH(CH2CH3)2; or, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl or -CH(CH2CH3)2.

[0065] In some implementations, R 4 and R 5 Independently, it is H, methyl, ethyl, n-propyl, isopropyl, n-butyl, -CH(CH2CH3)2, cyclopropyl, cyclopentyl, cyclohexyl, cyclooctyl, phenyl, or benzyl; for example, R 5 Independently for H, R 4 It can be methyl, ethyl, n-propyl, isopropyl, n-butyl, -CH(CH2CH3)2, cyclopropyl, cyclopentyl, cyclohexyl, cyclooctyl, phenyl or benzyl.

[0066] In some implementations, R 6 and R 7 Independently, it is H or phenyl; for example, R. 6 Independently for H, R 7 It is independently phenyl.

[0067] In some embodiments, the chiral nitrogen ligand may be selected from one or more of the following: L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L8, L19 and L20, or their enantiomers; preferably L16 or L12, or their enantiomers.

[0068]

[0069] In some embodiments, when the compound shown in Formula I is different from the compound shown in Formula II, the chiral nitrogen ligand is preferably L16 or its enantiomer. When the compound shown in Formula I is the same as the compound shown in Formula II, the chiral nitrogen ligand is preferably L12 or its enantiomer.

[0070] In some embodiments, the electrodes in the electrochemical asymmetric coupling reaction include a cathode electrode and an anode electrode. The anode electrode is one or more of iron, zinc, aluminum, platinum, copper, nickel, and magnesium, preferably iron or aluminum, and most preferably iron. The cathode electrode is one or more of platinum, gold, silver, copper, iron, palladium, magnesium, nickel foam, titanium, carbon, and stainless steel, preferably one or more of nickel, platinum, carbon, gold, titanium, and stainless steel, and most preferably stainless steel and nickel.

[0071] In some embodiments, when the compound shown in Formula I is the same as the compound shown in Formula II, the anode electrode is iron and the cathode electrode is stainless steel.

[0072] In some embodiments, when the compound shown in Formula I is not the same as the compound shown in Formula II, the anode electrode is iron and the cathode electrode is nickel.

[0073] In some embodiments, the electrolyte is a conventional electrolyte used in this type of reaction in the art, preferably one or more of quaternary ammonium salts (e.g., one or more of Et4NBF4, n-Bu4NBF4, Et4NPF6, n-Bu4NPF6, Et4NClO4, n-Bu4NClO4, Et4NOAc, n-Bu4NOAc, Et4NOTs, n-Bu4NOTs, n-Bu4NI, and H4NCl), sodium salts (e.g., one or more of NaCl, NaBr, NaI, and NaOAc), and lithium salts (e.g., LiBr and / or LiCl); more preferably one or more of n-Bu4NBF4, n-Bu4NPF6, Et4NOTs, n-Bu4NI, LiBr, and NaI, and most preferably NaI.

[0074] In some embodiments, the solvent is a conventional solvent used in this type of reaction in the art, preferably one or more of amide solvents (e.g., DMF and / or DMAc), halocarbon solvents (e.g., dichloromethane and / or trichloromethane), nitrile solvents (e.g., acetonitrile) and alcohol solvents (e.g., one or more of methanol, ethanol and isopropanol); more preferably one or more of DMF, DMAc and acetonitrile; and most preferably DMF or DMAc.

[0075] In some embodiments, the Co salt is one or more of Co(I) compounds (e.g., CoCl(PPh3)2), Co(II) compounds (e.g., one or more of CoI2, CoCl2, CoBr2·glyme, Co(OAc)2, and Co(C2O4)2), and Co(III) compounds (e.g., Co(acac)3); preferably one or more of CoI2, CoCl2, CoBr2·glyme, Co(OAc)2, CoCl(PPh3)2, Co2(acac)3, and Co(C2O4)2; most preferably CoI2.

[0076] In some embodiments, a desiccant is also added, which may be a conventional desiccant in the art, such as one or more of Na2SO4, MgSO4 and molecular sieves, with molecular sieves being the most preferred.

[0077] In some embodiments, the molar concentration of the compound of Formula I in the solvent may be a conventional molar concentration in the art, preferably 0.01-1 mol / L, more preferably 0.02-0.5 mol / L (e.g. 0.06-0.25 mol / L).

[0078] In some embodiments, the molar concentration of the compound of Formula II in the solvent may be a conventional molar concentration in the art, preferably 0.01-1 mol / L, more preferably 0.02-0.8 mol / L (e.g. 0.06-0.5 mol / L).

[0079] In some embodiments, the molar concentration of the electrolyte in the solvent may be a conventional molar concentration in the art, preferably 0.01-1 mol / L, more preferably 0.02-0.6 mol / L (e.g. 0.06-0.25 mol / L).

[0080] In some embodiments, the molar ratio of the electrolyte to the compound shown in Formula I can be a conventional molar ratio in the art, preferably 1:1 to 1:10 (e.g., 1:1 to 2:5).

[0081] In some embodiments, when the compound shown in Formula I is not the same as the compound shown in Formula II, the molar ratio of the compound shown in Formula I to the compound shown in Formula II is 1:1 to 5:1 (e.g., 1:1 to 2:1).

[0082] In some embodiments, when the compound shown in Formula I is the same as the compound shown in Formula II, the molar ratio of the total amount of the compound shown in Formula I and the compound shown in Formula II to the chiral nitrogen ligand can be a conventional molar ratio in the art, preferably 1:1-10:1 (e.g. 5:1-7:1).

[0083] In some embodiments, when the compound shown in Formula I is not the same as the compound shown in Formula II, the molar ratio of the compound shown in Formula I to the chiral nitrogen ligand may be a conventional molar ratio in the art, preferably 1:1-10:1 (e.g. 5:1-7:1).

[0084] In some embodiments, the molar ratio of the Co salt to the chiral nitrogen ligand can be a conventional ratio in the art, preferably 1:1 to 1:5 (e.g., 1:2).

[0085] In some embodiments, the current value of the electrochemical asymmetric coupling reaction is 0.1-20 mA (e.g., 1-6 mA).

[0086] In one embodiment of the present invention, the electrochemical asymmetric coupling reaction is preferably carried out at 0-150°C, more preferably at 0-80°C (e.g., 10-30°C).

[0087] In some embodiments, when the chiral nitrogen ligand is a compound of formula IV, the compound of formula III is in the R configuration; when the chiral nitrogen ligand is an enantiomer of the compound of formula IV (e.g., L12), the compound of formula III is in the S configuration.

[0088] In one aspect of the present invention, when the absolute configuration of the chiral nitrogen ligand is the same as the absolute configuration of the enantiomer of L12 as described above, the absolute configuration of the compound of formula III is the R configuration.

[0089] The present invention also relates to a catalyst composition comprising the chiral nitrogen ligand as described above and the Co salt as described above.

[0090] In one embodiment of the present invention, the chiral nitrogen ligand in the catalyst composition described above is selected from one or more of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L8, L19 and L20, or their enantiomers; preferably L8 or L12;

[0091]

[0092] In one embodiment of the present invention, the Co salt in the catalyst composition is selected from one or more of CoI2, CoCl2, CoBr2·glyme, Co(OAc)2, CoCl(PPh3)2, Co2(acac)3 and Co(C2O4)2.

[0093] In one embodiment of the present invention, the molar ratio of the Co salt to the chiral nitrogen ligand in the composition having electrochemical asymmetric catalysis is 1:1 to 1:5 (e.g., 1:2).

[0094] In one embodiment of the present invention, the chiral nitrogen ligand in the catalyst composition is partially or completely complexed with the compound shown in Formula IV, i.e., it exists in the form of a complex.

[0095] In one embodiment of the present invention, the catalyst composition may be a catalyst composition for electrochemical asymmetric catalysis.

[0096] The present invention also relates to a compound or its enantiomer as shown in Formula V.

[0097]

[0098] in,

[0099] R 8 For H, C1-C 10 Alkyl, C3-C 15 cycloalkyl, C6-C 10 Aryl or phenyl-substituted C1-C 10 alkyl;

[0100] X is a halogen.

[0101] In some embodiments, the compound or its enantiomer as shown in Formula V as described above, when X is a halogen, is preferably Br or I, and most preferably I.

[0102] In some embodiments, the compound or its enantiomer as shown in Formula V as described above, when R 8 For C1-C 10 Alkyl or phenyl substituted C1-C 10 When alkyl, the C1-C 10 Alkyl or phenyl substituted C1-C 10 C1-C in alkyl groups 10 The alkyl group can be C1-C6 alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl or -CH(CH2CH3)2; another example is methyl.

[0103] In some implementations, when R8 For C3-C 15 In the case of cycloalkyl groups, the C3-C 15 Cycloalkyl groups can be C3-C 12 cycloalkyl groups, such as cyclopropyl, cyclopentyl, cyclohexyl, and cyclooctyl.

[0104] In some implementations, when R 8 For C6-C 10 In the aryl case, the C6-C 10 The aryl group is either phenyl or naphthyl.

[0105] In some implementations, when R 8 C1-C substituted with phenyl 10 When alkyl; the C1-C substituted with phenyl 10 The alkyl group is benzyl.

[0106] In some embodiments, the compound or its enantiomer represented by Formula V may be a compound or its enantiomer represented by Formula VI.

[0107]

[0108] Wherein, X can be F, Cl, Br, or I, with I being the preferred choice.

[0109] In some embodiments, the cobalt complexes described above can be prepared by the following method: by reacting the chiral nitrogen ligands described above with the cobalt compound described above in a solvent via a self-assembly reaction.

[0110] The present invention also provides the use of the catalyst composition as described above or the compound as shown in Formula V or its enantiomers in asymmetric synthesis, preferably as a catalyst in the electrochemical asymmetric coupling reaction as described above.

[0111] In some embodiments, the conditions and operating methods of the asymmetric synthesis may be as described above for the conditions and operating methods of the asymmetric coupling method.

[0112] Unless otherwise specified, the terms used in this invention have the following meanings:

[0113] In this specification, groups and their substituents may be selected by those skilled in the art to provide stable structural moieties and compounds. When a substituent is described by a conventional chemical formula written from left to right, the substituent also includes chemically equivalent substituents obtained when the structural formula is written from right to left.

[0114] Certain chemical groups defined herein are preceded by simplified symbols to indicate the total number of carbon atoms present in the group. For example, C1-C6 alkyl refers to an alkyl group having a total of 1, 2, 3, 4, 5, or 6 carbon atoms as defined below. The total number of carbon atoms in the simplified symbols does not include carbons that may be present in substituents of the group.

[0115] In this paper, the numerical ranges defined in the substituents, such as 0 to 4, 1-4, 1 to 3, etc., indicate the integers within that range, such as 1-6 being 1, 2, 3, 4, 5, 6.

[0116] Except as otherwise specified, when used in the specification and claims of this application, the following terms shall have the following meanings.

[0117] The terms “one or more” or “one or more kinds” refer to 1, 2, 3, 4, 5, 6, 7, 8, 9 or more.

[0118] The term "comprising" is an open-ended expression, meaning it includes the contents specified in this invention, but does not exclude other aspects.

[0119] The term "substituted" refers to the substitution of one or more hydrogen atoms on a particular atom by a substituent, including deuterium and hydrogen variants, provided that the valence state of the particular atom is normal and the substituted compound is stable.

[0120] Generally, the term "substituted" indicates that one or more hydrogen atoms in a given structure are substituted by a specific substituent. Further, when the group is substituted by more than one of the substituents, the substituents are independent of each other; that is, the more than one substituent can be different or the same. Unless otherwise indicated, a substituent can be substituted at each substituted position of the substituted group. When more than one position in a given structural formula can be substituted by one or more substituents selected from a specific group, the substituents can be substituted at the same or different positions.

[0121] In various parts of this specification, the substituents of the compounds disclosed herein are disclosed according to the type or scope of the groups. In particular, this invention includes every independent secondary combination of the respective members of these group types and scopes. The term "C" x -C y "Alkyl" refers to a straight-chain or branched saturated hydrocarbon containing x to y carbon atoms. For example, the terms "C1-C6 alkyl" or "C 1-6 "alkyl" specifically refers to independently disclosed methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl; "C" 1-4"Alkyl" specifically refers to independently disclosed methyl, ethyl, C3 alkyl (i.e. propyl, including n-propyl and isopropyl), and C4 alkyl (i.e. butyl, including n-butyl, isobutyl, sec-butyl, and tert-butyl).

[0122] The term "halogen" is selected from F, Cl, Br or I.

[0123] The term "alkoxy group" refers to the group -OR X , where R X It is an alkyl group as defined above.

[0124] When a listed substituent does not specify which atom it is attached to in a compound included but not specifically mentioned in the general chemical formula, such a substituent may be bonded to any of its atoms. Combinations of substituents and / or their variants are permitted only if such combinations produce stable compounds.

[0125] When a listed group does not explicitly indicate that it has a substituent, the group refers only to the unsubstituted group. For example, when "C1-C4 alkyl" is not preceded by the qualifier "substituted or unsubstituted", it refers only to "C1-C4 alkyl" itself or "unsubstituted C1-C4 alkyl".

[0126] Linking substituents are described in various parts of this invention. When the structure clearly requires a linking group, the Markush variable listed for that group should be understood as the linking group. For example, if the structure requires a linking group and the Markush group definition for that variable lists "alkyl", then it should be understood that "alkyl" represents a linked alkylene group.

[0127] In some specific structures, when an alkyl group is clearly indicated as a linking group, then the alkyl group represents a linked alkylene group. For example, the C1-C6 alkyl in the group “halogenated-C1-C6 alkyl” should be understood as C1-C6 alkylene.

[0128] The term "alkylene" refers to a saturated divalent hydrocarbon group obtained by removing two hydrogen atoms from a saturated straight-chain or branched hydrocarbon group. Examples of alkylene groups include methylene (-CH2-), ethylene {including -CH2CH2- or -CH(CH3)-}, isopropylene {including -CH(CH3)CH2- or -C(CH3)2-}, and so on.

[0129] In this application, as a group or part of other groups (e.g., in halogen-substituted alkyl groups), the term "alkyl" means a saturated aliphatic hydrocarbon group comprising a branched or straight chain having a specified number of carbon atoms; for example, a straight-chain or branched saturated hydrocarbon chain containing 1 to 30 carbon atoms; or, for example, a C1-C6 alkyl group. As defined in "C1-C6 alkyl," it includes groups comprising 1, 2, 3, 4, 5, or 6 carbon atoms in a straight-chain or branched structure. Wherein, propyl is a C3 alkyl group (including isomers, such as n-propyl or isopropyl); butyl is a C4 alkyl group (including isomers, such as n-butyl, sec-butyl, isobutyl or tert-butyl); pentyl is a C5 alkyl group (including isomers, such as n-pentyl, 1-methyl-butyl, 1-ethyl-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, isopentyl, tert-pentyl or neopentyl); and hexyl is a C6 alkyl group (including isomers, such as n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl).

[0130] The term “halogenated alkyl” refers to an alkyl group that has been substituted with one or more halogens, such as trifluoromethyl, wherein “multiple”, “halogen” and “alkyl” are as defined above.

[0131] The term "cycloalkyl" refers to a saturated monocyclic or polycyclic carbocyclic substituent consisting only of carbon and hydrogen atoms, which can be connected to the rest of the molecule via a single bond through any suitable carbon atom; when polycyclic, it can be a fused ring system, a bridged ring system, or a spiro ring system (i.e., the two geminal hydrogens on the carbon atom are replaced by alkylene groups). In one embodiment, a monovalent saturated cycloalkyl group having 3-30 ring carbon atoms, more preferably 3-7 carbon atoms, is preferred. Typical monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl.

[0132] In this application, the term "cycloalkenyl" refers, either on its own or as part of another substituent, to an unsaturated, non-aromatic group containing a double bond. It is a monocyclic, polycyclic, or bridged carbocyclic substituent containing a partially unsaturated double bond, and can be connected to the rest of the molecule via a single bond through any suitable carbon atom; when polycyclic, it can be a fused or spirocyclic system (i.e., two union hydrogens on the carbon atom are replaced by alkylene groups) of either a bridged or spirocyclic system. In some embodiments, "C2-C30 cycloalkenyl" preferably refers to a non-aromatic group containing a single double bond and having 3-7 ring carbon atoms, more preferably 3-6 carbon atoms, such as cyclopropenyl, cyclobutenyl, cyclopentenyl, or cyclohexenyl. In some embodiments, "cycloalkenyl" is a monocyclic, unsaturated carbocyclic alkenyl group ("5-6 membered cycloalkenyl") having 5 to 6 ring atoms.

[0133] The term "heterocyclic alkyl" refers to a saturated monocyclic group having a heteroatom, preferably a 3- to 7-membered saturated monocyclic group containing one, two, or three cyclic heteroatoms independently selected from N, O, and S. Examples of heterocyclic alkyl groups include: pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydropyridyl, tetrahydropyrrolidinyl, azaheptanyl, thiazolyl, azoleyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazine, azaheptanyl, diazaheptanyl, oxonitroheptanyl, dioxopentyl, dioxohexyl, etc. Preferred heterocyclic groups are 1,3-dioxopentyl and 1,4-dioxohexyl.

[0134] The term "aryl" refers to an all-carbon aromatic group having a specified number of carbon atoms and a fully conjugated π-electron system (e.g., when it is bicyclic or tricyclic, each ring satisfies Hückel's rule). It can be monocyclic or fused, typically having 6-20 carbon atoms, preferably 6-14 carbon atoms, and most preferably 6 carbon atoms. Examples of aryl groups include, but are not limited to: monocyclic aryl groups such as C6 aryl (phenyl), bicyclic aryl groups such as C6 aryl... 10 Aryl (naphthyl), tricyclic aryl, such as C 14 Aryl (phenanthryl and anthracene).

[0135] The term "heteroaryl" refers to an aromatic group containing a heteroatom, which can be monocyclic or fused ring, preferably containing 1-4 5-10 membered heteroaryl groups independently selected from N, O, and S, including but not limited to pyrroloyl, furanyl, thiophene, indolyl, imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyridinyl, pyrazinyl, pyridazinyl, quinolinyl, isoquinolinyl, (benzo)oxazolyl, (benzo)furanyl, (benzo)thiophene, (benzo)thiazolyl, and triazolyl. In one embodiment, it typically contains one or more 5-6 membered monocyclic heteroaryl groups independently selected from N, O, and S. In another embodiment, "heteroaryl" is a 5-6 membered heteroaryl group, wherein the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3.

[0136] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0137] The reagents and raw materials used in this invention are all commercially available.

[0138] Compared with existing technologies, this invention provides a solution that combines chiral ligands with transition metal catalysis to obtain optically active axially chiral biaryl compounds under electrochemical reduction conditions. This synthetic method features high selectivity, mild reaction conditions, environmental friendliness, high yield, and good purity. Therefore, this invention has significant practical value. Attached Figure Description

[0139] Figure 1 Thermoellipsoid diagram of Co complex crystals Detailed Implementation

[0140] The present invention will be further described below through specific embodiments, but it should not be construed as limiting the scope of the above-mentioned subject matter of the present invention to the following embodiments. All technologies implemented based on the above content of the present invention fall within the scope of the present invention.

[0141] All reagents used in this article were purchased directly without further purification. Column chromatography used 100-200 mesh or 300-400 mesh silica gel. Thin-plate chromatography was performed using UV or iodine staining. All reagents were purchased from TCI, Sigma-Aldrich, Adamas-Beta, J&K, Bidex Pharmaceuticals, Jiuding Pharmaceuticals, and Anaiji Chemicals, all at the highest commercially available purity. Sodium iodide was purchased from TCI without purification (99%), and cobalt iodide was purchased from Alfa Aesar (≥99%) without further purification. Ultra-dry solvents were purchased from J&K without further purification. ¹H NMR and… 13 C{ 1 H NMR was obtained in tests conducted on Agilent AV 400, Varian Inova 400, and Bruker 400 (400MHz and 100MHz, respectively). 19 F NMR was obtained using an Agilent AV400, Varian Inova 400 (376 MHz). NMR standards were calibrated using TMS or deuterated solvents.

[0142] General Steps

[0143] Method A: Self-coupling (0.3 mmol)

[0144]

[0145] Reaction procedure (0.3 mmol scale): In a glove box, add a stir bar to the reaction tube of the IKA 2.0 electrochemical synthesizer, then add 2a (0.3 mmol, 1.0 equiv.), cobalt iodide (0.03 mmol, 10 mol%), L18 (0.06 mmol, 20 mol%), and sodium iodide (0.3 mmol, 1.0 equiv.). Molecular sieve (70 mg) and N,N-dimethylformamide (5 mL) were used in an IKA reactor with an iron electrode as the anode and a stainless steel electrode as the cathode. The reaction apparatus was stirred at room temperature for 30 minutes. After stirring, an electric current of 1 mA was applied for 24 hours. After the reaction was completed, the reaction solution was passed through diatomaceous earth and washed with dichloromethane. The solvent was removed by rotary evaporation, and the product was purified by rapid column chromatography.

[0146] Method B: Cross-coupling (0.3 mmol)

[0147]

[0148] Reaction procedure: In a glove box, add a stir bar to the reaction tube of the IKA 2.0 electrochemical synthesizer, then add 1a (0.3 mmol, 1.0 equiv.), 6a (0.6 mmol, 2.0 equiv.), cobalt iodide (0.45 mmol, 15 mol%), L12 (0.09 mmol, 30 mol%), and sodium iodide (0.3 mmol, 1.0 equiv.). Molecular sieve (70 mg) and N,N-dimethylacetamide (5 mL) were used in an IKA 2.0 reactor with an iron electrode as the anode and a stainless steel electrode as the cathode. The reaction apparatus was stirred at room temperature for 30 minutes, and after stirring, an electric current of 1 mA was applied for 24 hours. After the reaction was completed, the reaction solution was diluted with ethyl acetate (80 mL), neutralized with dilute hydrochloric acid, separated, and the organic phase was washed with saturated ammonium chloride (20 mL × 3) water. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by rotary evaporation. The product was then purified by rapid column chromatography.

[0149] Method C: Self-coupling (5 mmol)

[0150] Reaction procedure (5 mmol scale): In a glove box, add a stir bar to the electrochemical reaction tube, then add 2a (5 mmol, 1.0 equiv.), cobalt iodide (0.5 mmol, 10 mol%), L18 (1 mmol, 20 mol%), and sodium iodide (2 mmol, 40 mol%). Molecular sieve (250 mg), N,N-dimethylformamide (20 mL), an iron electrode as the anode and a nickel foam electrode as the cathode (4 × 4 cm) were installed in the reaction tube.2 The reaction apparatus was placed at room temperature and stirred for 30 minutes. After stirring, an electric current of 6 mA was applied and the reaction was carried out for 72 hours. After the reaction was completed, the reaction solution was passed through diatomaceous earth and washed with dichloromethane. The solvent was removed by rotary evaporation and purified by rapid column chromatography to obtain the corresponding product.

[0151] Method D: Cross-coupling (5 mmol)

[0152] Reaction procedure (5 mmol scale): In a glove box, add a stir bar to the electrochemical reaction tube, then add 1a (5 mmol, 1.0 equiv.), 6a (10 mmol, 2.0 equiv.), cobalt iodide (0.75 mmol, 15 mol%), L18 (1.5 mmol, 30 mol%), and sodium iodide (2 mmol, 40 mol%). Molecular sieve (250 mg), N,N-dimethylacetamide (20 mL), an iron electrode as the anode and a nickel foam electrode as the cathode (4 × 4 cm) were installed in the reaction tube. 2 The reaction apparatus was placed at room temperature and stirred for 30 minutes. After stirring, an electric current of 6 mA was applied and the reaction was carried out for 72 hours. After the reaction was completed, the reaction solution was passed through diatomaceous earth and washed with dichloromethane. The solvent was removed by rotary evaporation and purified by rapid column chromatography to obtain the corresponding product.

[0153] Example 1

[0154]

[0155] (4a) (57.6 mg, 78%) was obtained by method A. 1 H NMR (400MHz, CDCl3) δ8.32(d,J=8.8Hz,2H),8.04(d,J=8.8Hz,2H),7.96(d,J=8.4Hz, 2H),7.60–7.50(m,2H),7.36–7.14(m,8H),7.13–7.03(m,2H),6.67(d,J=8.0Hz,4H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ165.5,150.6,140.5,135.3,133.0,129.3,128.4,128.2,127.4,127.1,127.0,126.3,125.6,121.3.[α] D 27.2=38.26 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 9.199 min (small), tR = 13.320 min (large).

[0156] (4a) (1.11 g, 90%) enantiomers with a ratio of 95:5 were obtained by method C and identified by chiral high performance liquid chromatography.

[0157] Example 2

[0158]

[0159] 4b (1.11g, 90%) was obtained by method A. 1 H NMR (400MHz, CDCl3) δ8.27(d,J=8.8Hz,2H),7.96(d,J=8.8Hz,2H),7.72(s,2H),7.2 8–7.05(m,10H),6.66(d,J=7.6Hz,4H),2.79(q,J=7.6Hz,4H),1.30(t,J=7.6Hz,6H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ165.6,150.7,144.3,140.7,135.6,131.5,129.2,128.3,127.7,127.4,126.3,126.0,125.8,125.48,121.37,28. 95,15.12.IR(neat):1731,1623,1591,1487,1379,1330,1278,1229,1186.1160,1100,1049,956,922,895,827,793,741,714,687,496cm -1 HRMS (DART) theoretical value C 38 H 34 O4N[M+NH4] + :568.2482, Experimental value:568.2486.[α] 29.3 =32.78 (c=1.0, CHCl3). Enantiomer ratio = 94:6, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 9.035 min (small), tR = 11.565 min (large).

[0160] Example 3

[0161]

[0162] The raw material was obtained as 2c (85.5 mg, 89%) with 4c (2c) by method A, mp = 187.7-189.1℃. 1 H NMR (400MHz, CDCl3) δ8.04(d,J=8.4Hz,2H),7.86–7.72(m,4H),7.35(d,J=7.2Hz,4H),7.25(d,J=8.4Hz,2 H),7.17–6.98(m,4H),6.86(d,J=7.6Hz,4H),6.92–6.81(m,4H),6.80–6.70(m,2H)6.40(d,J=7.6Hz,4H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ165.4,150.6,140.7,140.6,140.2,135.6,132.1,129.3,129.0,128.6,128.0,127.9,127.5,126.8,126.8,12 6.7,125.9,125.6,121.4.IR(neat):1725,1619,1591,1489,1466,1327,1283,1231,1187,1160,1097,1064,893,832,760,687,499cm -1 HRMS (DART) theoretical value C 46 H 34 O4N[M+NH4] + Experimental value: 664.2482; [α] 27.3 = -23.26 (c = 1.0, CHCl3). Enantiomer ratio = 95:5, identified by chiral high performance liquid chromatography (Daicel IG column, n-hexane:isopropanol = 90:10, flow rate 0.7 mL / min, T = 25℃, λ = 214 nm): tR = 35.81 min (small), tR = 39.01 min (large).

[0163] Example 4

[0164]

[0165] The raw material was obtained as 2d (62.9 mg, 76%) for 4d using method A. 1H NMR (400MHz, CDCl3) δ8.30(d,J=8.4Hz,2H),7.91(d,J=8.4Hz,2H),7.30–7.05(m,10H),6.96(d,J=9.2Hz,2H),6.72(d,J=7.6Hz,4H),3.93(s,6H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ165.3,159.2,150.6,141.0,137.0,129.2,129.0,128.2,127.1,126.9,125.4,124.4,121.4,119.8,105. 9,55.4.IR(neat):2970,1727,1618,1474,1407,1377,1275,1233,1187,1096,1058,1026,926,854,783,745,723,688,557,501cm -1 HRMS (DART) theoretical value C 36 H 27 O6[M+H] + Experimental value: 555.1802. [α] 29.8 =44.96 (c=0.8, CHCl3). Enantiomer ratio = 96:4. Identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 80:20, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 9.461 min (small), tR = 16.322 min (large).

[0166] Example 5

[0167]

[0168] The raw material was 2e, which was obtained by method A with 4e (60.5 mg, 61%). 1 H NMR (400MHz, CDCl3) δ8.29(d,J=8.4Hz,2H),7.89(d,J=8.8Hz,2H),7.27–7.18(m,6H),7.15–7.05(m,4H),6.95(d,J=9.6Hz,2H),6. 72(d,J=8.0Hz,4H),5.93–5.80(m,2H),5.13–4.99(m,4H),4.11(t,J=6.4Hz,4H),2.28(dd,J=14.8,7.2Hz,4H),2.01–1.77(m,4H). 13 C{ 1H}NMR (101MHz, CDCl3) δ165.5,158.8,150.8,141.1,137.8,137.1,129.3,129.1,128.3,127.2,126.9,125.6,124.4,121.5,120.1,115.5,10 6.7,67.4,30.2,28.4.IR(neat):2934,1735,1616,1465,1429,1378,1328,1274,1233,1178,1095,1054,1022,918,854,745,688,563,499cm -1 HRMS (DART) theoretical value C 44 H 38 O6[M+H] + Experimental value: 685.2561; [α] 28.6 =26.59 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 7.716 min (small), tR = 8.982 min (large).

[0169] Example 6

[0170]

[0171] The 4f (66.7 mg, 86%) raw material was obtained by method A as 2f. 1 H NMR (400MHz, CDCl3) δ8.24(d,J=8.4Hz,2H),7.99(d,J=8.8Hz,2H),7.86(d,J=8.4Hz,2H),7.39(d,J =8.4Hz,2H),7.23–7.14(m,4H),7.11–7.04(m,2H),6.98(s,2H),6.63(d,J=7.6Hz,4H),2.26(s,6H). 13 C{ 1H}NMR(101MHz, CDCl3)δ165.8,150.7,134.0,137.0,133.6,133.3,130.6,129.3,128.1,128.0,127.1,126.3,125.6,125.5, 121.4,22.1.IR(neat):2919,1739,1593,1489,1452,1313,1234,1184,1160,1096,1053,942,842,743,719,687,502,427cm -1 HRMS (DART) theoretical value C 36 H 27 O4[M+H] + Experimental value: 523.1904; [α] 26.4 =46.09 (c=1.0, CHCl3). Enantiomer ratio = 93:7, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 98:2, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 21.870 min (small), tR = 26.988 min (large).

[0172] Example 7

[0173]

[0174] 4g (49.1mg, 62%) of raw material was obtained by method A, which was 2g. 1 H NMR (400MHz, CDCl3) δ8.29(d,J=8.4Hz,2H),8.05(d,J=8.4Hz,2H),7.97(dd,J=9.2,5. 6Hz,2H),7.40–7.31(m,2H),7.26–7.19(m,4H),7.14–7.08(m,2H),6.81–6.70(m,6H). 13 C{ 1 H}NMR(101MHz, CDCl3) δ165.1,161.3(d,J=249.5Hz),150.5,139.2(d,J=6.1Hz),133.8(d,J=9.1Hz),132.3,130.7 (d,J=9.1Hz),129.3,128.5,127.8,125.77,125.68(d,J=2.0Hz),121.3,118.7(d,J=25.3Hz),110.7(d,J=22.2Hz). 19F NMR(376MHz, CDCl3)δ-111.57.IR(neat):2972,1738,1628,1593,1510,1489 ,1442,1313,1231,1181,1121,1092,952,843,741,720,687,531,484,433cm -1 HRMS (DART) theoretical value C 34 H 21 O4 F2[M+H] + Experimental value: 531.1402; [α] 29.0 =23.40 (c=0.9, CHCl3). Enantiomer ratio = 95:5, identified by chiral high performance liquid chromatography (Chiralpak OJ (4.6*250mm), CO2:IPA = 85:15, flow rate 1.3mL / min, T = 26℃, λ = 214nm): tR = 13.859min (large), tR = 17.425min (small).

[0175] Example 8

[0176]

[0177] The raw material was obtained by method A for 4 hours (55.1 mg, 58%), which was 2 hours. 1 H NMR (400MHz, CDCl3) δ8.36–8.21(m,4H),7.40(d,J=6.8Hz,2H),7.25–7.04(m,10H),6.62(d,J =8.0Hz,4H),3.27–3.04(m,4H),1.88–1.75(m,8H),1.54–1.38(m,4H),0.96(t,J=6.8Hz,6H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ165.6,150.6,141.4,139.2,133.8,133.5,129.1,128.1,126.6,126.6,125.9(2C),125.5,124.2,121.3,33.3, 32.1,30.7,22.7,14.1.IR(neat):2925,1715,1592,1488,1456,1366,1316,1257,1188,1159,1115,1091,828,777,742,688,543,502cm -1 HRMS (DART) theoretical value C 44 H 43 O4[M+H]+ Experimental value: 635.3156. [α] 29.8 =28.03 (c=1.0, CHCl3). Enantiomer ratio = 95:5, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T=25℃, λ=254nm): tR=7.759min (small), tR=9.244min (large).

[0178] Example 9

[0179]

[0180] The 4i (59.0 mg, 71%) raw material was obtained by method A as 2i, mp = 125.4-127.6℃. 1 H NMR(400MHz, CD2Cl2)δ8.41(d,J=9.2Hz,2H),8.17(d,J=9.2Hz,2H),7.20–7.00(m,8 H),6.85(d,J=7.6Hz,2H),6.66(d,J=8.4Hz,2H),6.59(d,J=7.6Hz,4H),3.97(s,6H). 13 C{ 1 H}NMR(101MHz,CD2Cl2)δ165.6,155.4,150.7,139.9,133.9,129.1,127.6,127.4,127.1,125.6,125.2,122.2,121.3,1 19.2,105.9,55.8.IR(neat):1722,1591,1489,1461,1408,1379,1320,1259,1187,1160,1104,931,834,766,739,687cm -1 HRMS (DART) theoretical value C 36 H 30 O6N[M+H] + Experimental value: 572.2068; [α] 28.9 =49.13 (c=0.6, CHCl3). Enantiomer ratio = 98:2, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 18.271 min (large), tR = 24.085 min (small).

[0181] Example 10

[0182]

[0183] 4j (56.0 mg, 72%) of raw material was obtained by method A, which was 2j. 1 H NMR (400MHz, CDCl3) δ8.17 (s, 2H), 8.12 (d, J = 8.4Hz, 2H), 7.60 (t, J = 7.6Hz, 2 H),7.30–7.17(m,8H),7.14–7.07(m,2H),6.70(d,J=8.0Hz,4H),2.85(s,6H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ165.6,150.6,139.0,134.6,134.5,133.2,129.2,128.1,127.9,126.6(2C),126.5,125.5,124.3,121 .4,19.7.IR(neat):1722,1593,1489,1374,1346,1218,1186,1161,1141,1112,1056,939,893,835,760,724,686,497,422cm -1 HRMS (DART) theoretical value C 36 H 27 O4[M+H] + Experimental value: 523.1904. [α] 30.4 =34.82 (c=0.9, CHCl3). Enantiomer ratio = 92:8, identified by chiral high performance liquid chromatography (Daicel Chiralpak OD-H column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 6.342 min (large), tR = 8.264 min (small).

[0184] Example 11

[0185]

[0186] 4k (69.6 mg, 72%) was obtained by method A. The raw material was 2k, mp = 193.5-195.5℃. 1 H NMR (400MHz, CDCl3) δ8.12(s,2H),8.03(d,J=8.4Hz,2H),7.72(d,J=7.6Hz,4H),7.65–7.07(m,12H),7.13–6.96(m,6H),6.16(d,J=8.4Hz,4H). 13 C{ 1H}NMR(101MHz, CDCl3)δ166.6,150.2,140.9,137.3,135.0,133.6,132.0,131.8,129.7,129.0,129.0,128.6,128.2,127.8,127.7,127.5,1 27.2,121.1.IR(neat):2986,1744,1590,1490,1451,1415,1258,1221,1185,1159,1087,1065,975,897,846,745,688,601,574,504,482cm -1 HRMS (DART) theoretical value C 46 H 31 O4[M+H] + Experimental value: 647.2217; [α] 29.2 =15.98 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 4.724 min (small), tR = 8.120 min (large).

[0187] 4k (1.17 g, 73%) was obtained by method C, with a starting material of 2k and an enantiomer ratio of 95:5. The enantiomers were identified by chiral high-performance liquid chromatography.

[0188] Example 12

[0189]

[0190] 4 liters (67.9 mg, 65%) of raw material were obtained by method A, with 2 liters being raw material. 1 H NMR(400MHz, CDCl3)δ8.07(s,2H),7.98(d,J=8.0Hz,2H),7.65–7.45(m,8H),7.45–7.28(m ,6H),7.10–6.90(m,6H),6.12(d,J=7.6Hz,4H),2.74(q,7.2Hz,4H),1.31(t,J=7.2Hz,6H). 13 C{ 1H}NMR(101MHz, CDCl3)δ167.6,151.1,144.7,139.2,138.2,135.7,134.4,132.8,130.4,129.9,129.8,129.0,128.6,128.4,127.9,126 .3,126.1,122.0,29.6,16.8.IR(neat):2965,1739,1591,1489,1256,1225,1185,1159,1089,1065,1023,899,831,743,688,600,505cm -1 HRMS (DART) theoretical value C 50 H 42 O4N[M+H] + Experimental value: 720.3108; [α] 26.2 =58.37 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T=25℃, λ=254nm): tR=11.817min (small), tR=14.752min (large).

[0191] Example 13

[0192]

[0193] The raw material was 2m, with 4m (69.2mg, 63%) obtained by method A. 1 H NMR (400MHz, CDCl3) δ8.05 (s, 2H), 7.96 (d, J = 8.0Hz, 2H), 7.64–7.43 (m, 8H), 7.45–7.25 (m, 6H), 7.05 –6.90(m,6H),6.10(d,J=7.6Hz,4H),2.66(t,J=7.6Hz,4H),1.84–1.50(m,4H),0.98(t,J=7.2Hz,6H). 13 C{ 1H}NMR(101MHz, CDCl3)δ166.7,150.3,142.3,138.3,137.4,134.9,133.6,132.0(2C),129.6,128.9,128.7,128.1,127.7,127.6,12 7.1,125.5,121.2,37.8,24.7,13.9.IR(neat):2925,1745,1590,1489,1256,1222,1185,1159,1086,900,832,741,687,601,505cm -1 HRMS (DART) theoretical value C 52 H 46 O4N[M+H] + Experimental value: 748.3421; [α] 30.3 = -1.84 (c = 1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 7.690 min (small), tR = 9.609 min (large).

[0194] Example 14

[0195]

[0196] The raw material was 2n (72.1 mg, 66%), which was obtained by method A. 1 H NMR(400MHz, CDCl3)δ8.05(s,2H),7.96(d,J=8.4Hz,2H),7.68–7.44(m,8H),7.41–7.30(m ,6H),7.07–6.90(m,6H),6.05(d,J=8.0Hz,4H),3.03–2.93(m,2H),1.31(d,J=6.8Hz,12H). 13 C{ 1H}NMR(101MHz, CDCl3)δ166.7,150.3,148.4,138.5,137.4,134.9,133.6,132.0(2C),129.5,129.0,128.9,128.1,127.7,127.6,127.1,1 26.7,125.4,121.2,34.0,24.2,24.1.IR(neat):2963,1743,1590,1490,1253,1185,1159,1088,1023,900,831,739,686,600,578,507cm -1 HRMS (DART) theoretical value C 52 H 43 O4[M+H] + Experimental value: 731.3156; [α] 26.8 =3.85 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 6.738 min (small), tR = 10.526 min (large).

[0197] Example 15

[0198]

[0199] The raw material was 200 mg (72.9 mg, 65%) obtained by method A. 1 H NMR (400MHz, CDCl3) δ8.10(s,2H),8.00(d,J=8.0Hz,2H),7.71–7.34(m,14H),7.10–7.34(m,6H),6.08(d,J=6.8Hz,4H),1.42(s,18H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ166.7,150.7,150.3,138.2,137.3,134.9,133.6,132.0(2C),129.5,128.9,128.8,128.2,127.7,127.6,127.1,125.5(2 C),121.2,34.7,31.5.IR(neat):2958,1747,1590,1490,1257,1222,11 86,1159,1114,1084,1064,1022,975,899,833,746,687,607,564,508cm-1 HRMS (DART) theoretical value C 54 H 50 O4N[M+NH4] + Experimental value: 776.3734; [α] 28.9 =4.19 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 5.461 min (small), tR = 8.355 min (large).

[0200] Example 16

[0201]

[0202] The raw material was 2p (63.6mg, 60%) and 4p (63.6mg, 60%) was obtained by method A. 1 H NMR (400MHz, CDCl3) δ8.06 (s, 2H), 7.98 (d, J = 8.4Hz, 2H), 7.67–7.46 (m, 8H) ,7.46–7.35(m,2H),7.12–6.94(m,10H),6.19(d,J=8.0Hz,4H),3.88(s,6H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ166.8,159.4,150.3,136.9,134.8,133.6,133.3,132.1,131.8,130.2,129.6,129.0,128.1,127.7,127.6,127.0,125 .5,121.1,114.1,55.5.IR(neat):2931,1743,1608,1512,1489,1288,1247,1222,1182,1158,1085,1064,1027,899,831,743,687,599,506cm -1 HRMS (DART) theoretical value C 48 H 38 O6N[M+NH4] + Experimental value: 724.2694. [α] 27.3= -1.05 (c = 1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Daicel Chiralpak ADH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 11.948 min (small), tR = 16.206 min (large).

[0203]

[0204] The raw material was 2q, which was 4q (79.8 mg, 67%) obtained by method A. 1 H NMR (400MHz, CDCl3) δ8.16 (s, 2H), 8.04 (d, J = 8.4Hz, 2H), 7.83–7.33 (m, 24H), 7.10–6.94 (m, 6H), 6.19 (d, J = 8.0Hz, 4H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ166.7,150.2,140.7,140.6,139.9,136.9,135.0, 133.6,132.0,131.7,129.7,129.4,129.0,128.9,128.2,127.9,127.5,127 .5,127.3,127.3,127.2,125.5,121.0.IR(neat):3027,1744,1589,1486, 1257,1221,1185,1158,1088,1006,974,901,838,733,688,601,579,503cm -1 HRMS (DART) theoretical value C 58 H 38 O4Na[M+Na] + Experimental value: 821.2662. [α] 29.5 = -45.66 (c = 1.0, CHCl3). Enantiomer ratio = 99:1, identified by chiral high performance liquid chromatography (Daicel IG column, n-hexane:isopropanol = 90:10, flow rate 0.7 mL / min, T = 25℃, λ = 214 nm): tR = 24.95 min (small), tR = 35.90 min (large).

[0205] Example 17

[0206]

[0207] The 4r (61.1 mg, 60%) raw material was obtained by method A as 2r.1 H NMR (400MHz, CDCl3) δ7.94 (s, 2H), 7.89 (d, J = 8.0Hz, 2H), 7.57–7.28 (m, 6H), 7.40 (d, J = 8. 4Hz,2H),7.34–7.28(m,2H),7.15–7.06(m,4H),7.01–6.85(m,6H),6.03(d,J=7.6Hz,4H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ165.4,161.6(d,J=247.5Hz),149.07,135.8(d,J=3.0Hz),135.1,133.9,132.5,130 .9,130.7,129.6(d,J=8.1Hz),128.7,128.0,127.0(2C),126.4,126.3,124.6,119.8,114.5(d,J=21.2Hz). 19 F NMR(376MHz, CDCl3)δ-111.54.IR(neat):2972,1743,1591,1510,1489,1258,1221,1185,1158,1086,976,901,836,743,687,598,548,511cm -1 HRMS (DART) theoretical value C 46 H 32 O4NF2[M+NH4] + Experimental value: 700.2294; [α] 28.5 =20.87 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 10.123 min (small), tR = 17.499 min (large).

[0208] Example 18

[0209]

[0210] The 4s (55.3 mg, 52%) raw material was obtained by method A as 2s. 1H NMR (400MHz, CDCl3) δ8.02(s,2H),7.98(d,J=8.0Hz,2H),7.64–7.52(m,6H),7.51–7.36(m,8H),7.09–6.94(m,6H),6.11(d,J=8.0Hz,4H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ166.4,150.1,139.3,136.1,135.1,134.0,133.5,132.0,131.5,130.3,129.8,129.1,128.8,128.2,128. 1,127.5,127.5,125.7,120.8.IR(neat):2970,1742,1592,1476,1229,1186,1159.1094,1062,901,827,746,687,601,504,448cm -1 HRMS (DART) theoretical value C 46 H 29 O4Cl2[M+H] + Experimental value: 715.1437; [α] 30.4 = -6.43 (c = 1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 6.762 min (small), tR = 8.297 min (large).

[0211] Example 19

[0212]

[0213] 4t (63.8mg, 58%) of raw material was obtained by method A, with 2t being raw material. 1 H NMR(400MHz, CDCl3)δ8.15–7.96(m,8H),7.77(d,J=8.0Hz,4H),7.65–7.58(m, 2H),7.56–7.40(m,4H),7.10–6.94(m,6H),6.13(d,J=8.0Hz,4H),2.66(s,6H). 13 C{ 1H}NMR(101MHz, CDCl3)δ197.8,166.3,150.1,145.7,136.3,136.2,135.4,133.5,132.2,131.1,130.0,129.2,129.1,128.7,128.4,128.2, 127.8,127.5,125.7,120.7,26.8.IR(neat):2971,1740,1680,1590,1489,1256,1184,1159,1089,1066,957,901,832,739,687,602,504cm -1 HRMS (DART) theoretical value C 50 H 38 O6N[M+NH4] + Experimental value: 748.2694; [α] 25.3 = -33.76 (c = 1.0, CHCl3). Enantiomer ratio = 98:2, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 80:20, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 14.571 min (small), tR = 24.868 min (large).

[0214] Example 20

[0215]

[0216] The raw material yielded 2 units of 4 units (73.7 mg, 65%) using method A. 1 H NMR (400MHz, CDCl3) δ8.19(d,J=8.0Hz,4H),8.10(s,2H),8.03(d,J=8.0Hz,2H),7.76(d,J=8.0Hz, 4H),7.65–7.58(m,2H),7.55–7.40(m,4H),7.10–6.96(m,6H),6.14(d,J=7.6Hz,4H),3.97(s,6H). 13 C{ 1H}NMR (101MHz, CDCl3) δ166.9,166.3,150.1,145.5,136.3,135.4,133.5,132.2,131.2,130.0,129.9,129.4,129.1,129.0,128.3,128.2,127. 7,127.5,125.7,120.8,52.3.IR(neat):1718,1590,1488,1433,1275,1 223,1183,1159,1105,1019,975,902,859,775,746,710,687,602,486cm -1 HRMS (DART) theoretical value C 50 H 38 O8N[M+NH4] + Experimental value: 780.2592; [α] 28.1 = -28.99 (c = 1.0, CHCl3). Enantiomer ratio = 98:2, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 18.151 min (small), tR = 23.833 min (large).

[0217] Example 21

[0218]

[0219] The 4v (64.4mg, 55%) raw material was obtained by method A as 2v. 1 H NMR (400MHz, CDCl3) δ8.10 (s, 2H), 8.04 (d, J = 8.4Hz, 2H), 7.83–7.74 (s, 8H), 7.6 4(t,J=7.2Hz,2H),7.58–7.42(m,4H),7.12–6.90(m,6H),6.09(d,J=7.6Hz,4H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ166.2,150.0,144.6,136.0,135.4,133.5,132.2,131.3,130.1(q,J=32.3Hz),13 0.0,129.4,129.1,128.4,128.3,127.8,127.5,125.8,125.6(q,J=4.0Hz),124.2(q,J=275.7Hz),120.7. 19F NMR(376MHz, CDCl3)δ-62.42.IR(neat):2986,1744,1591,1490,1404,1322,1258,1223,1160,1107,1063,1018,901,850,744,687,612,504cm -1 HRMS (DART) theoretical value C 48 H 29 O4F4[M+H] + Experimental value: 783.1965; [α] 29.9 =4.51 (c = 1.0, CHCl3). Enantiomer ratio = 98:2, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 6.253 min (small), tR = 8.122 min (large).

[0220] Example 22

[0221]

[0222] The raw material was obtained as 2w (4w, 81.5mg, 68%) using method A. 1 H NMR (400MHz, CDCl3) δ8.18 (s, 2H), 8.04 (d, J = 8.0Hz, 2H), 7.93 (s, 2H), 7.75 –7.55(m,14H),7.50–7.31(m,8H),7.10–6.77(m,4H),6.16(d,J=7.6Hz,4H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ166.8,150.2,141.6,141.3,140.8,137.2,135.5,135.1,133.6,132.1,131.9,129.7,129.1,129.0,128.8,128 .2,127.9(2C),127.6,127.5,127.3,126.5,125.5,121.0.IR(neat):1743,1589,1482,1249,1185,1158,1090,894,804,756,688,509cm -1 HRMS (DART) theoretical value C 58 H 39 O4[M+H] + Experimental value: 799.2843. [α] 25.81= -9.66 (c = 1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 5.893 min (small), tR = 7.831 min (large).

[0223] Example 23

[0224]

[0225] 4x (65.9 mg, 62%) of raw material was obtained by method A, which was 2x. 1 H NMR (400MHz, CDCl3) δ8.12 (s, 2H), 8.02 (d, J = 8.0Hz, 2H), 7.66–7.48 (m, 4H), 7.48–7. 37(m,4H),7.33–7.21(m,4H),7.11–6.90(m,8H),6.20(d,J=8.0Hz,4H),3.85(s,6H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ166.7,159.8,150.4,142.3,137.2,135.1,133.6,132.1,131.9,129.7,129.1,128.3,127.9,127.6,126.3,125.6,121. 6,121.1,114.4,113.7,55.4.IR(neat):1742,1588,1487,1455,1262,1 233,1184,1158,1094,1044,992,956,879,785,743,688,556,492,468cm -1 HRMS (DART) theoretical value C 48 H 38 O6N[M+NH4] + Experimental value: 724.2694; [α] 27.7 =17.83 (c=1.0, CHCl3). Enantiomer ratio = 97:3, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 6.955 min (small), tR = 10.594 min (large).

[0226] Example 24

[0227]

[0228] The raw material yielded 4y (84.1 mg, 78%) of the sample was 2y using method A. 1 H NMR (400MHz, CDCl3) δ8.07 (s, 2H), 8.02 (d, J = 8.4Hz, 2H), 7.70–7.56 (m, 2H), 7.51–7.41 (m, 4H), 7.24–6.83 (m, 12H), 6.23 (d, J = 7.6Hz, 4H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ166.1,164.2(d,J=13.1Hz),161.7(d,J=13.1Hz),150.1,143.9(t,J=10.1Hz),135.4,135.1,13 3.4,132.3,131.0,129.9,129.2,128.3,128.0,127.4,125.8,120.7,112.1(dd,J=19.2Hz,8.1Hz),103.2(t,J=25.3Hz) 19 FNMR(376MHz, CDCl3)δ-109.26.IR(neat):2963,1743,1590,1490,1253,1185,1159,1088,1023,900,831,739,686,600,578,507cm -1 HRMS (DART) theoretical value C 46 H 30 O4NF4[M+NH4] + Experimental value: 736.2105. [α] 30.1 =17.01 (c=1.0, CHCl3). Enantiomer ratio = 97:3, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 6.003 min (small), tR = 10.431 min (large).

[0229] Example 25

[0230]

[0231] The raw material was 2z (70.4mg, 63%) and 4z (4z of raw material) were obtained by method A. 1H NMR (400MHz, CDCl3) δ8.30–8.10(m,4H),8.12–7.80(m,10H),7.69–7.41(m,10H),7.10–6.83(m,6H),6.11(d,J=7.2Hz,4H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ166.7,150.2,138.3,137.2,135.2,133.6,133.4,1 32.7,132.0,131.9,130.1,129.0,128.2,128.2(2C),127.9,127.8(2C),12 7.6,127.4,127.2,126.6,126.2,125.5,121.0.IR(neat):1751,1587,1488 ,1258,1238,1183,1159,1129,1083,993,897,858,820,742,688,506,476cm -1 HRMS (DART) theoretical value C 54 H 38 O4N[M+NH4] + Experimental value: 764.2795; [α] 26.7 = -55.87 (c = 1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 9.465 min (small), tR = 10.551 min (large).

[0232] Example 26

[0233]

[0234] The 4aa (64.0 mg, 65%) raw material was obtained by method A, which was 2aa. 1 H NMR(400MHz, CDCl3)δ7.95–7.85(m,4H),7.51(t,J=7.2Hz,2H),7.43–7.28(m,4H),7.22–7.12(m,4H),7.10 –7.02(m,2H),6.53(d,J=8.0Hz,4H),5.97(s,2H),7.63–7.53(m,4H),7.31–7.20(s,4H),1.96–1.62(m,8H). 13 C{ 1H}NMR(101MHz, CDCl3)δ166.9,150.6,139.8,138.1,134.6,133.5,131.8,131.7,129.1,127.8,127.6,127.5,127.5,127.4,126.6,125 .5,121.2,30.5,25.7,23.1,22.0.IR(neat):2924,1745,1588,1489,1431,1250,1185,1158,1132,1076,894,840,744,687,604,503cm -1 HRMS (DART) theoretical value C 46 H 39 O4[M+H] + Experimental value: 655.2843; [α] 25.5 =48.59 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 4.730 min (small), tR = 5.270 min (large).

[0235] Example 27

[0236]

[0237] 4ab (56.1 mg, 75%) was obtained by method A. The raw material was 2ab, mp = 163.5-164.8℃. 1 H NMR (400MHz, CDCl3) δ9.00(d,J=3.2Hz,2H),8.58(d,J=9.2Hz,2H),8.36(d,J=9.2Hz,2 H),7.51(d,J=8.4Hz,2H),7.36–7.20(m,6H),7.16–7.09(m,2H),6.73(d,J=8.0Hz,4H). 13 C{ 1H}NMR(101MHz, CDCl3)δ164.6,152.5,150.3,149.4,139.6,135.2,130.2,129.9,129.4,128.1,127.6,126.0,122.3,121.1.IR(neat):2 922,1717,1588,1564,1489,1454,1404,1383,1323,1260,1239,128,1186,1100,1064,1024,927,899,844,786,738,685,554,496,462cm -1 HRMS (DART) theoretical value C 32 H 21 O4N2[M+NH4] + Experimental value: 497.1496; [α] 25.9 =45.97 (c=1.0, CHCl3). Enantiomer ratio = 93:7. Identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane:isopropanol = 80:20, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 13.933 min (large), tR = 16.187 min (small).

[0238] Example 28

[0239]

[0240] 7a (106.6 mg, 72%) was obtained by method B from raw materials 1a and 6a. 1 H NMR (400MHz, CDCl3) δ8.18(d,J=8.4Hz,1H),7.98(d,J=8.8Hz,1H),7.91(d,J=8.4Hz,1H),7.84–7.75(m,2H),7.53–7.44 (m,1H),7.33–7.06(m,11H),7.01(d,J=8.4Hz,1H),6.95–6.83(m,2H),6.78(d,J=7.6Hz,2H),4.90(s,2H),4.86(s,2H). 13 C{ 1H}NMR (101MHz, CDCl3) δ167.6,153.2,137.5,137.1,135.5,135.2,134.0,133.1,129.4,129. 1,129.0,128.2(2C),128.0(2C),127.8(2C),127.7,127.4,126.7(2C),126.5,126.4,125.1, 123.7,122.9,115.2,70.9,66.7.IR(neat):2926,1716,1620,1591,1504,1453,1377,1327,1 272,1232,1122,1081,1046,1018,961,915,868,805,766,735,696,590,563,486,464,433cm -1 HRMS (DART) theoretical value C 35 H 30 O3N2[M+NH4] + Experimental value: 512.2220; [α] 27.5 =7.56 (c=1.0, CHCl3). Enantiomer ratio = 95:5, identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 7.105 min (small), tR = 7.813 min (large).

[0241] 7a (1.89 g, 76%) was obtained by method D. The raw materials were 1a and 6a, with an enantiomer ratio of 95:5, and were identified by chiral high performance liquid chromatography.

[0242] Example 29

[0243]

[0244] 7b (126.7 mg, 79%) was obtained by method B from raw materials 1a and 6b. 1H NMR (400MHz, CDCl3) δ8.16(d,J=8.8Hz,1H),7.97(d,J=8.8Hz,1H),7.91(d,J=8.0Hz,1H),7.72(d,J=8.8Hz,1H),7.55–7.43(m,2H),7. 35–6.97(m,9H),6.93–6.84(m,4H),6.77(d,J=7.6Hz,2H),5.00–4.76(m,4H),2.04–1.92(m,1H),1.02–0.91(m,2H),0.80–0.65(m,2H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ167.7,152.6,139.0,137.6,137.2,135.5,135.2,133.1,132.4,129. 3,129.0,128.6,128.2(2C),128.0,127.9,127.8(2C),127.7,127.4,126.7,126.6,126.3,125 .4,125.2,123.9,122.9,115.5,71.0,66.7,15.4,9.0.IR(neat):3030,1703,1594,1498,145 4,1377,1322,1271,1232,1121,1083,1045,1024,967,904,865,822,765,732,694,627,462cm -1 HRMS (DART) theoretical value C 38 H 30 O3Na[M+Na] + Experimental value: 557.2087; [α] 23.4 = -1.11 (c = 1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 6.523 min (small), tR = 7.796 min (large).

[0245] Example 30

[0246]

[0247] 7c (134.0 mg, 77%) was obtained by method B from raw materials 1a and 6c. 1H NMR (400MHz, CDCl3) δ8.17(d,J=8.8Hz,1H),7.96(d,J=8.8Hz,1H),7.90(d,J=8.4Hz,1H),7.74(d,J=9.2Hz,1H),7.58(s,1H),7.52–7.45(m, 1H),7.33–7.02(m,10H),6.96–6.85(m,3H),6.82–6.74(m,2H),4.94– 4.79(m,4H),2.64–2.52(m,1H),1.99–1.66(m,5H),1.53–1.21(m,5H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ167.7,152.7,143.2,137.6,137.4,135.5,135.2,133.1,132.7,129.4,1 29.0,128.2(3C),128.0,127.9(2C),127.8,127.7,127.4,127.0,126.7,126.6,126.4,125.0,124 .5,122.9,115.3,71.0,66.7,44.4,34.5,34.4,27.0,26.3.IR(neat):3062,2922,2850,2117,17 05,1595,1498,1451,1377,1326,1272,1233,1121,1075,1027,907,873,822,797,766,732,695cm -1 HRMS (DART) theoretical value C 41 H 36 O3Na[M+Na] + Experimental value: 599.2557. [α] 26.9 = -1.84 (c = 1.0, CHCl3). Enantiomer ratio = 97:3, identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 5.664 min (small), tR = 6.185 min (large).

[0248] Example 31

[0249]

[0250] The raw materials for 7 days (112.2 mg, 66%) were obtained by method B for 1a and 6d. 1H NMR (400MHz, CDCl3) δ8.10(d,J=8.4Hz,1H),7.90(d,J=8.8Hz,1H),7.83(d,J=8.4Hz,1H),7.74–7.66(m,2H),7.44–7.38(m,1H),7 .22–6.99(m,10H),6.92(d,J=8.8Hz,1H),6.85–6.79(m,2H),6.71(d,J=7.2Hz,2H),5.10(s,2H),4.82–4.72(m,4H),2.00(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ171.0,167.5,153.6,137.3,136.9,135.4,135.2,133.8,133.0,1 31.0,129.4,129.0,128.7,128.2(3C),128.1,128.0,127.8(2C),127.7,127.5,126.7(2C) ,126.4,125.6,122.9,115.5,70.8,66.7,66.6,21.1.IR(neat):2946,1722,1618,1593,14 99,1454,1374,1319,1268,1237,1131,1074,1023,984,906,857,805,734,695,628,460cm -1 HRMS (DART) theoretical value C 38 H 34 O5N[M+NH4] + Experimental value: 584.2431; [α] 28.0 = -0.98 (c = 1.0, CHCl3). Enantiomer ratio = 95:5, identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 13.323 min (small), tR = 15.302 min (large).

[0251] Example 32

[0252]

[0253] 7e (102.0 mg, 65%) was obtained by method B from raw materials 1a and 6e. 1H NMR (400MHz, CDCl3) δ8.18(d,J=8.8Hz,1H),7.99(d,J=8.8Hz,1H),7.93(d,J=8.4Hz,1H),7.77(d,J=8.8Hz,1H),7.70(s,1H), 7.56–7.43(m,1H),7.36–7.05(m,10H),7.03–6.72(m,6H),5.74(d,J=17.6Hz,1H),5.25(d,J=10.8Hz,1H),5.02–4.67(m,4H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ167.6,153.4,137.4,136.9,135.4,135.2,133.7,133.0(2C),12 9.5,129.1,129.0,128.2(2C),128.0,127.8,127.7,127.4,126.7(2C),126.5,126.4,125 .4,123.9,123.0,115.4,113.4,70.8,66.7.IR(neat):2867,2122,1704,1620,1591,149 8,1454,1377,1327,1271,1233,1121,1077,1044,988,905,829,797,766,735,696,463cm -1 HRMS (DART) theoretical value C 37 H 29 O3[M+H] + Experimental value: 521.2108; [α] 26.2 = -10.69 (c = 1.0, CHCl3). Enantiomer ratio = 95:5, identified by chiral high performance liquid chromatography (Daicel Chiralpak ADH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 6.932 min (small), tR = 7.750 min (large).

[0254] Example 33

[0255]

[0256] 7f (121.5 mg, 77%) was obtained by method B from raw materials 1a and 6f, mp = 135.2–137.5 °C. 1H NMR (400MHz, CDCl3) δ8.16(d,J=8.8Hz,1H),7.98(d,J=8.4Hz,1H),7.92(d,J=8.0Hz,1H),7.71(d,J=9 .2Hz,1H),7.52–7.42(m,1H),7.34–7.03(m,10H),6.97–6.78(m,6H),4.93–4.83(m,4H),3.88(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ167.6,156.1,151.8,137.6,137.1,135.5,135.2,133.1,130.1,129.5,129. 0,128.2(2C),128.0(2C),127.8(2C),127.1,127.4,126.8,126.7(2C),126.3,123.5,119.3,116.1,1 06.0,71.2,66.7,55.3.IR(neat):2857,2320,1703,1624,1591,1503,1453,1378,1324,1272,1241,1 168,1115,1077,1053,1024,965,908,849,822,796,766,736,696,633,608,569,522,494,458,424cm -1 HRMS (DART) theoretical value C 36 H 28 O4[M+H] + Experimental value: 524.1982; [α] 26.5 =8.40 (c=1.0, CHCl3). Enantiomer ratio = 93:7, identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 8.053 min (small), tR = 9.451 min (large).

[0257] Example 34

[0258]

[0259] 7g (90.3mg, 54%) was obtained by method B. 1H NMR (400MHz, CDCl3) δ8.17(d,J=8.8Hz,1H),7.86(d,J=8.4Hz,1H),7.69(d,J=8.4Hz,1H ),7.27–7.07(m,10H),6.99–6.75(m,7H),4.97–4.80(m,4H),3.91(s,3H),3.89(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ167.5,159.1,156.1,151.7,137.7,137.4,136.9,135.6,130.1,129. 5,129.4,128.4,128.2,127.8(2C),127.4,127.2,126.8,126.7(2C),126.6,123.8,119.4,11 9.2,116.2,106.0,105.9,71.2,66.5,55.4,55.3.IR(neat):2934,2119,1701,1620,1596,15 02,1475,1454,1375,1335,1274,1232,1195,1168,1121,1074,1027,853,822,788,734,696cm -1 HRMS (DART) theoretical value C 37 H 31 O5[M+H] + Experimental value: 555.2166; [α] 27.7 =4.23 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 10.972 min (small), tR = 13.190 min (large).

[0260] Example 35

[0261]

[0262] The raw materials were 1a and 6g, mp = 148.5–151.3℃, obtained by method B for 7h (88.5 mg, 53%). 1H NMR (400MHz, CDCl3) δ8.54(d,J=1.2Hz,1H),8.21(d,J=8.8Hz,1H),8.01(d,J =8.8Hz,1H),7.94(d,J=8.0Hz,1H),7.89(d,J=9.2Hz,1H),7.72(dd,J=8.8,1 .6Hz,1H),7.58–7.48(m,1H),7.33–7.08(m,9H),7.02(d,J=8.8Hz,1H),6.92 –6.90(m,2H),6.78(d,J=7.6Hz,2H),4.95(s,2H),4.85(s,2H),3.93(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ167.4,155.0,137.0,136.4,136.2,135.3,135.2,132.8,131.4,130 .9,128.9,128.3(2C),128.2,128.1,127.9,127.8(2C),127.6,127.4,126.8,126.6,126.4, 125.8,125.2,125.1,122.9,115.4,70.6,66.8,52.1.IR(neat):2947,2119,1701,1620,159 6,1502,1475,1454,1375,1274,1232,1195,1168,1121,1074,1027,853,822,788,734,696cm -1 HRMS (DART) theoretical value C 37 H 29 O5[M+H] + Experimental value: 553.2010; [α] 24.0 = -7.59 (c = 1.0, CHCl3). Enantiomer ratio = 95:5, identified by chiral high performance liquid chromatography (Daicel Chiralpak ADH column, n-hexane:isopropanol = 80:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 13.560 min (small), tR = 20.140 min (large).

[0263] Example 36

[0264]

[0265] 7i (110.2 mg, 72%) raw materials 1c and 6a were obtained by method B. 1H NMR(400MHz, CDCl3)δ8.16–8.15(m,2H),7.84(d,J=8.8Hz,2H),7.63–7.56(m,1H),7.40–7.12(m,11H) ,7.08–7.03(m,1H),7.02–6.94(m,2H),6.81(d,J=7.2Hz,2H),4.96(s,2H),4.90(s,2H),2.87(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ167.8,153.3,137.6,135.5,135.2,134.5,134.4,134.2,133.1,129.2,129.1,1 28.6,128.4,128.2(2C),127.9,127.8,127.5,127.4,126.7(2C),126.4,126.3,125.2,124.2,123.6,12 3.1,115.3,70.8,66.6,19.6.IR(neat):2857,2320,1703,1624,1591,1503,1453,1378,1324,1272,124 1,1168,1116,1077,1053,1024,965,908,849,822,796,766,736,696,633,608,569,522,494,458,424cm -1 HRMS (DART) theoretical value C 36 H 29 O3[M+H] + Experimental value: 509.2111; [α] 24.5 =8.78 (c=1.0, CHCl3). Enantiomer ratio = 95:5. Identified by chiral high performance liquid chromatography (Daicel Chiralpak ADH column, n-hexane:isopropanol = 95:5, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 8.426 min (small), tR = 9.027 min (large).

[0266] Example 37

[0267]

[0268] 7j (114.3 mg, 75%) raw materials 1b and 6a were obtained by method B. 1H NMR(400MHz, CDCl3)δ8.10(d,J=8.8Hz,1H),7.92(d,J=8.8Hz,1H),7.84–7.60(m,3H),7.38–6 .98(m,12H),6.96–6.88(m,2H),6.78(d,J=7.2Hz,2H),4.92(s,2H),4.84(s,2H),2.19(s,3H). 13 C NMR (101MHz, CDCl3) δ167.8,153.2,137.6,136.4(2C),135.5,134.1,133.5,133.3,130.1 ,129.3,129.1(2C),128.2(2C),128.0,127.9,127.8(2C),127.4,126.7,126.6,126.5,125 .5,125.2,123.7,123.1,115.3,70.8,66.7,22.0.IR(neat):3031,2119,1705,1622,1593 ,1507,1453,1376,1316,1267,1235,1121,1072,1047,1017,968,907,844,806,733,695cm -1 HRMS (DART) theoretical value C 36 H 29 O3[M+H] + Experimental value: 509.2111; [α] 26.8 =11.65 (c=1.0, CHCl3). Enantiomer ratio = 94:6, identified by chiral high performance liquid chromatography (Daicel IG column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 7.647 min (small), tR = 8.424 min (large).

[0269] Example 38

[0270]

[0271] 7k (111.3mg, 71%) raw materials were obtained by method B for 1d and 6a. 1H NMR (400MHz, CDCl3) δ8.05 (dd, J=15.6Hz, 8.8Hz, 2H), 7.72 (d, J=8.8Hz, 2H), 7.25–7.01 (m, 10H) ,6.97–6.78(m,4H),6.71(d,J=7.2Hz,2H),4.85(s,2H),4.76(s,2H),2.66(s,3H),2.10(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ167.8,153.1,137.6,136.6,135.8,135.5,134.1(2C),133.5,132.7,1 30.9,129.1,129.0,128.8,128.2,128.1,127.9,127.7,127.4,126.7,126.4,125.3,125.2,124 .9,123.9,123.6,123.4,115.2,70.8,66.6,21.8,19.6.IR(neat):2926,1704,1621,1593,150 7,1454,1371,1316,1268,1243,1131,1081,1056,1019,906,859,804,731,694,576,495,428cm -1 HRMS (DART) theoretical value C 37 H 31 O3[M+H] + Experimental value: 523.2263. [α] 28.0 =3.50 (c=1.0, CHCl3). Enantiomer ratio = 94:6, identified by chiral high performance liquid chromatography (Daicel IG column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 7.383 min (small), tR = 8.310 min (large).

[0272] Example 39

[0273]

[0274] 7i (100.4 mg, 64%) was obtained by method B, with raw materials consisting of 1 g and 6a. 1H NMR (400MHz, CDCl3) δ8.45(d,J=8.8Hz,1H),8.16(d,J=8.8Hz,1H),7.79(d,J=8.8Hz,2H),7.34–7.07(m,10 H),7.03–6.89(m,3H),6.84(d,J=7.6Hz,2H),6.78(d,J=7.6Hz,2H),4.91(s,2H),4.86(s,2H),4.02(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ167.7,155.4,153.2,137.5,136.4,135.5,134.1,134.0,129.6,129 .2,129.1,128.2,128.1,127.9,127.8,127.5,127.4,126.7,126.6,126.4,125.7,125.2,123 .6,123.3,122.1,119.9,115.3,105.5,70.9,66.6,55.7.IR(neat):3032,2947,1722,1619,1 592,1500,1455,1374,1319,1268,1238,1131,1073,1023,984,907,857,806,733,695,628cm -1 HRMS (DART) theoretical value C 36 H 29 O4[M+H] + Experimental value: 525.2060; [α] 25.4 =2.36 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Daicel IG column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 12.106 min (large), tR = 14.020 min (small).

[0275] Example 40

[0276]

[0277] 7m (96.5mg, 61%) of raw materials were obtained by method B as 1f and 6a. 1H NMR (400MHz, CDCl3) δ8.19(d,J=8.8Hz,1H),7.86(d,J=8.8Hz,1H),7.78(d,J=8.8Hz,2H),7.33–7.09(m,11 H),7.01(d,J=8.4Hz,1H),6.95–6.84(m,3H),6.78(d,J=7.2Hz,2H),4.91(s,2H),4.85(s,2H),3.88(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ167.5,159.1,153.1,137.5,137.4,137.0,135.6,134.0,129.5,129 .3,129.1,128.4,128.2(2C),128.1,128.0,127.8,127.4,127.3,126.7,126.6,126.5,125. 1,123.7,123.3,119.4,115.3,105.9,70.9,66.6,55.4.IR(neat):2946,1722,1618,1593,1 499,1455,1373,1317,1268,1238,1131,1073,1022,984,906,857,805,733,695,628,459cm -1 HRMS (DART) theoretical value C 36 H 28 O4Na[M+Na] + Experimental value: 547.1880. [α] 25.1 =6.09 (c=1.0, CHCl3). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Daicel (Chiralpak ODH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 9.530 min (small), tR = 10.549 min (large).

[0278] Example 41

[0279]

[0280] 7n (97.7 mg, 62%) was obtained by method B from raw materials 1e and 6a. 1H NMR (400MHz, CDCl3) δ8.04(d,J=8.4Hz,1H),7.91(d,J=8.4Hz,1H),7.84–7.75(m,3H),7.34–6.99(m,1 1H), 6.93 (d, J = 4.8Hz, 2H), 6.79 (d, J = 7.2Hz, 2H), 6.51 (s, 1H), 4.92 (s, 2H), 4.86 (s, 2H), 3.36 (s, 3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ167.8,158.1,153.1,137.5,135.5,135.5,134.3,133.8,130.8,129 .6,129.5,129.3,129.1,128.2,128.1,128.0,127.8,127.7,127.4,126.7,126.5,125.1,12 4.2,123.7,123.1,120.1,115.2,106.1,70.9,66.67,55.0.IR(neat):2935,2117,1723,162 1,1593,1507,1454,1377,1316,1267,1220,1179,1124,1071,1030,908,845,807,734,695cm -1 HRMS (DART) theoretical value C 36 H 29 O4[M+H] + Experimental value: 525.2060. [α] 27.1 = -2.38 (c = 1.0, CHCl3). Enantiomer ratio = 86:14, identified by chiral high performance liquid chromatography (Daicel Chiralpak ADH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 8.876 min (large), tR = 10.466 min (small).

[0281] Example 42

[0282]

[0283] 7o (101.6 mg, 59%) of raw materials 1i and 6a were obtained by method B. 1H NMR (400MHz, CDCl3) δ8.18(d,J=8.4Hz,1H),7.85(d,J=8.4Hz,1H),7.79(d,J=8.8Hz,2H),7.33–7.07(m,11H),7.01(d,J=8.8Hz,1H),6.97–6.86(m,3H ),6.78(d,J=7.2Hz,2H),5.91–5.79(m,1H),5.11–4.97(m,2H),4.91(s,2H) ,4.85(s,2H),4.09(t,J=6.4Hz,2H),2.32–2.20(m,2H),1.99–1.81(m,2H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ167.5,158.5,153.0,137.7,137.5,137.3,137.0,135.6,134.0,129.5,129 .2,129.1,128.3,128.2(2C),128.1,127.9,127.7,127.4,127.2,126.7(2C),126.5,126.4,125.1, 123.6,123.3,119.6,115.4,115.3,106.6,70.9,67.3,66.5,30.2,28.4.IR(neat):2940,2117,170 1,1619,1502,1463,1377,1332,1272,1233,1177,1122,1073,1049,1017,909,855,805,733,695cm -1 HRMS (DART) theoretical value C 40 H 35 O4[M+H] + Experimental value: 579.2530; [α] 27.4 =2.94 (c=1.0, CHCl3). Enantiomer ratio = 95:5, identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 6.960 min (large), tR = 7.739 min (small).

[0284] Example 43

[0285]

[0286] 7o (122.7 mg, 72%) raw material was obtained by method B at 1h and 6a, mp = 133.7-135.4℃. 1 H NMR (400MHz, CDCl3) δ8.12(d,J=8.8Hz,1H),8.00(s,1H),7.92(d,J=8.8Hz,1H),7.70(d,J=7.2Hz,2H),7.55( d,J=7.6Hz,2H),7.46–6.92(m,15H),6.83(d,J=3.2Hz,2H),6.68(d,J=7.6Hz,2H),4.82(s,2H),4.77(s,2H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ167.6,153.2,140.6,140.3,137.5,137.1,135.6,135.5,134.1,132.3,129.5 ,129.2,129.0(2C),128.5,128.3,128.2,128.1,127.9,127.8,127.5,127.0,126.8,126.6,126.4,12 5.8,125.2,123.8,123.0,115.3,71.0,66.8.IR(neat):1720,1620,1592,1495,1451,1374,1332,128 3,1246,1228,1148,1085,1056,1021,914,890,837,801,760,725,691,609,588,570,500,459,432cm -1 HRMS (DART) theoretical value C 40 H 35 O4[M+H] + Experimental value: 571.2268; [α] 27.9 =5.86 (c=1.0, CHCl3). Enantiomer ratio = 96:4. Identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane:isopropanol = 90:10, flow rate 1 mL / min, T = 25℃, λ = 254 nm): tR = 10.511 min (small), tR = 11.709 min (large).

[0287] Example 44: Ligand Screening

[0288]

[0289] αReaction conditions: 1a or 2a (0.3 mmol, 1.0 equiv), cobalt iodide (10 mol%), ligand (20 mol%), tetrabutylammonium tetrafluoroborate (0.3 mmol, 1.0 equiv). Molecular sieve (70 mg) and N,N-dimethylformamide (5 mL) were used as reaction solvents. Electrolysis was performed at a constant current of 1 mA for 24 hours at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and nickel foam as the cathode. Conversion and yield were determined by 1H NMR spectroscopy, with mesitylene as an internal standard. The ee value of the product was determined by chiral HPLC.

[0290] Example 45: Cathode Screening a

[0291]

[0292]

[0293] a Reaction conditions: 2a (0.3 mmol, 1.0 equiv), cobalt iodide (10 mol%), ligand L15 (20 mol%), tetrabutylammonium tetrafluoroborate (0.3 mmol, 1.0 equiv). Molecular sieve (70 mg) and N,N-dimethylformamide (5 mL) were used as the reaction solvent. Electrolysis was performed at a constant current of 1 mA for 24 hours at room temperature in an IKA2.0 electrochemical reactor with an iron anode. Conversion and yield were determined by 1H NMR spectroscopy, with mesitylene as an internal standard. The ee value of the product was determined by chiral HPLC.

[0294] Example 46: Electrolyte Screening a

[0295]

[0296] a Reaction conditions: 2a (0.3 mmol, 1.0 equiv), cobalt iodide (10 mol%), ligand L15 (20 mol%), tetrabutylammonium tetrafluoroborate (0.3 mmol, 1.0 equiv). Molecular sieve (70 mg) and N,N-dimethylformamide (5 mL) were used as the reaction solvent. Electrolysis was performed at a constant current of 1 mA for 24 hours at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and stainless steel as the cathode. Conversion and yield were determined by 1H NMR spectroscopy, with mesitylene as an internal standard. The ee value of the product was determined by chiral HPLC.

[0297] Table S4 Screening of Solvent a

[0298]

[0299] a Reaction conditions: 2a (0.3 mmol, 1.0 equiv), cobalt iodide (10 mol%), ligand L15 (20 mol%), sodium iodide (0.3 mmol, 1.0 equiv). Molecular sieve (70 mg) and solvent (5 mL) were used as the reaction solvent. Electrolysis was performed at a constant current of 1 mA for 24 hours at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and stainless steel as the cathode. Conversion and yield were determined by 1H NMR spectroscopy, with mesitylene as an internal standard. The ee value of the product was determined by chiral HPLC.

[0300] Example 47: Screening of Co catalysts a

[0301]

[0302] a Reaction conditions: 2a (0.3 mmol, 1.0 equiv), cobalt catalyst (10 mol%), ligand L15 (20 mol%), sodium iodide (0.3 mmol, 1.0 equiv). Molecular sieve (70 mg) and N,N-dimethylformamide (5 mL) were used as the reaction solvent. Electrolysis was performed at a constant current of 1 mA for 24 hours at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and stainless steel as the cathode. Conversion and yield were determined by 1H NMR spectroscopy, with mesitylene as an internal standard. The ee value of the product was determined by chiral HPLC.

[0303] Example 48: Anode Screening a

[0304]

[0305] a Reaction conditions: 2a (0.3 mmol, 1.0 equiv), cobalt iodide (10 mol%), ligand L15 (20 mol%), sodium iodide (0.3 mmol, 1.0 equiv). Molecular sieve (70 mg) and N,N-dimethylformamide (5 mL) were used as the reaction solvent. Electrolysis was performed at a constant current of 1 mA for 24 hours at room temperature in an IKA2.0 electrochemical reactor with a stainless steel cathode. Conversion and yield were determined by 1H NMR spectroscopy, with mesitylene as an internal standard. The ee value of the product was determined by chiral HPLC.

[0306] Example 49: Screening of cross-coupled chiral nitrogen ligands

[0307]

[0308] a Reaction conditions: 1a (0.3 mmol, 1.0 equiv), 6a (0.6 mmol, 2.0 equiv), cobalt iodide (10 mol%), ligand L15 (20 mol%), sodium iodide (0.3 mmol, 1.0 equiv). Molecular sieve (70 mg) and N,N-dimethylacetamide (5 mL) were used as reaction solvents. Electrolysis was performed at a constant current of 1 mA for 24 hours at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and stainless steel as the cathode. Conversion and yield were determined by 1H NMR spectroscopy, with mesitylene as an internal standard. The ee value of the product was determined by chiral HPLC.

[0309] Example 50: Optimization of reaction conditions using 1a and 6a a

[0310]

[0311] a Reaction conditions: 1a (0.3 mmol, 1.0 equiv), 6a (0.6 mmol, 2.0 equiv), cobalt iodide (15 mol%), ligand L15 (30 mol%), sodium iodide (0.3 mmol, 1.0 equiv). Molecular sieve (70 mg) and N,N-dimethylacetamide (5 mL) were used as reaction solvents. Electrolysis was performed at a constant current of 1 mA for 24 hours at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and stainless steel as the cathode. Conversion and yield were determined by 1H NMR spectroscopy, with mesitylene as an internal standard. The ee value of the product was determined by chiral HPLC.

[0312] Example 51: Substrate Synthesis

[0313] Method I: Synthesis of 1-bromo-2-naphthoic acid phenyl ester substrates

[0314]

[0315] At 0°C, N,N-dimethylformamide (3.0 equiv) was added dropwise to a chloroform (0.2 M) solution containing phosphorus tribromide (5.0 equiv). After the addition was complete, the reaction mixture was stirred at room temperature for 2 h. After stirring, the reaction substrate S1 (1.0 equiv) was added to the reaction mixture and the temperature was raised to reflux, and the reaction was allowed to proceed for 2 h. After the reaction was completed, the reaction solution was cooled and quenched with saturated sodium hydroxide solution. The reaction mixture was separated, the aqueous phase was extracted with dichloromethane, the organic phases were combined, dried over anhydrous magnesium sulfate, concentrated, and the concentrate was purified by rapid column chromatography to obtain reaction intermediate S2.

[0316] S2 was dissolved in toluene (0.2 M), and 2,3-dichloro-5,6-dicyanobenzoquinone (3.0 equiv) was added to the toluene. The reaction mixture was heated to reflux, and samples were taken to monitor the reaction progress. After the reaction was completed, the reaction mixture was cooled, filtered through diatomaceous earth, and the filtrate was concentrated by rotary evaporation. The concentrate was purified by rapid column chromatography to obtain intermediate S3.

[0317] Intermediate S3 (S3 < 10 mmol) was dissolved in 70 mL of isopropanol. 4 mL of 2-methyl-2-butene was slowly added to the reaction mixture, followed by the slow addition of 100 mL of an aqueous solution of sodium chlorite (3.35 g, 39 mmol) and sodium dihydrogen phosphate (4.03 g, 33.6 mmol). After the addition was complete, the reaction mixture was stirred at room temperature for 24 h. After the reaction was complete, tert-butanol was removed by rotary evaporation. 25 mL of water was added to the mixture after the tert-butanol removal, and the mixture was washed with 20 mL of n-hexane. The pH of the concentrated washing solution was adjusted to 1, resulting in a large amount of solid. The solid was dissolved in ethyl acetate, and the mixture was separated. The aqueous phase was extracted with ethyl acetate, and the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent in the filtrate was removed by rotary evaporation to obtain intermediate S4.

[0318] S4 (1.0 equiv) was added to a dry round-bottom flask equipped with a stirrer and dissolved in dichloromethane. Under stirring, dicyclohexylcarbodiimide (1.0 equiv), 4-dimethylaminopyridine (1.0 equiv), and phenol (1.0 equiv) were added. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the reaction solution was filtered through diatomaceous earth, and the filtrate was collected and concentrated by rotary evaporation. The concentrated solution was purified by rapid column chromatography to obtain the final product S5.

[0319] Method II: Synthesis of phenyl 3-aryl(alkenyl)-1-bromo-2-naphthoic acid ester substrates

[0320]

[0321] Add 1-bromo-2-naphthoic acid (15.6 mmol, 1.0 equiv), N,N-dimethylformamide (25 mL), N-iodosuccinimide (18.7 mmol, 1.2 equiv), and palladium acetate (1.56 mmol, 0.1 equiv) to a dry 250 mL round-bottom flask equipped with a stirrer. Heat the reaction mixture to 100 °C and stir for 12 h. After the reaction is complete, cool the reaction mixture to room temperature and dilute with ethyl acetate. Add saturated sodium carbonate solution to the solution, separate the layers, extract the organic phase with saturated sodium carbonate, and combine the aqueous phases. Adjust the pH of the aqueous phase to 1; a large amount of solid appears. Add ethyl acetate to the solid, and it dissolves. Separate the mixture, extract the aqueous phase with ethyl acetate, combine the organic phases, dry to anhydrous magnesium sulfate, filter, and remove the solvent from the filtrate by rotary evaporation to obtain crude product S6, which can be used directly in the next step.

[0322] S6, HATU (31.2 mmol, 2.0 equiv), sodium phenolate (31.2 mmol, 2.0 equiv), N,N-diisopropylethylamine (31.2 mmol, 2.0 equiv), potassium carbonate (31.2 mmol, 2.0 equiv), and DMF (25 mL) were added to a dry 250 mL round-bottom flask equipped with a stir bar. The reaction mixture was heated to 100 °C and monitored by thin-plate chromatography. After the reaction was complete, the reaction mixture was filtered through diatomaceous earth. The filtrate was concentrated by rotary evaporation to remove the solvent, and the product S7 was purified by rapid column chromatography.

[0323] Add S7 (3 mmol, 1.0 equiv), potassium carbonate (2.0 equiv), tetraphenylphosphine palladium (0.15 mmol, 0.05 equiv), arylboronic acid (3 mmol, 1.0 equiv), tetrahydrofuran (3 mL), and water (3 mL) to a dry, 50 mL sealed tube equipped with a stir bar, then purge with nitrogen three times. Heat the reaction mixture to 100 °C and react for 12 h. After the reaction is complete, dilute the reaction mixture with ethyl acetate, separate the layers, extract the aqueous phase with ethyl acetate, combine the organic phases, dry to anhydrous magnesium sulfate, filter, concentrate by rotary evaporation, and purify the concentrate by rapid column chromatography to obtain product S8.

[0324] Method III: Synthesis of 1-bromo-2-naphthoic acid benzyl ester

[0325]

[0326] Add S4 (1.0 equiv), potassium carbonate (2.0 equiv), and benzyl bromide (1.5 euqiv) to a 250 mL round-bottom flask equipped with a stirrer. Heat the reaction mixture to 70 °C with stirring, and monitor the reaction using thin-plate chromatography. After the reaction is complete, cool the reaction mixture to room temperature, dilute it with water and ethyl acetate, separate the layers, extract the aqueous phase with ethyl acetate, combine the organic phases, extract the organic phase with saturated ammonium chloride aqueous phase, and separate the layers. Dry the organic phase with anhydrous magnesium sulfate, filter, concentrate the filtrate by rotary evaporation, and separate the concentrate by rapid column chromatography to obtain product S9.

[0327]

[0328] (1a) is obtained through method III. 1 H NMR (400MHz, CDCl3) δ8.43(d,J=8.4Hz,1H),7.85–7.73(m,2H),7.70–7.52(m,3H),7.49(d,J=7.2Hz,2H),7.43–7.30(m,3H),5.44(s,2H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ167.2,135.5,135.2,132.3,131.2,128.7,128.6,128.5,128.5,128.2,128.2,128.2,127.9,125.9,122.8,67.6.IR(ne at):2359,1732,1595,1495,1453,1381,1321,1263,1232,1171,1151,1 121,978,952,866,819,783,762,734,694,662,614,581,532,471,443cm -1 HRMS (ESI) theoretical value C 18 H 13 O2BrNa[M+Na] + 362.9991, Experimental value: 362.9990.

[0329]

[0330] Obtained via method III (1b), 1 H NMR (400MHz, CDCl3) δ8.10(s,1H),7.66–7.56(m.2H),7.50(d,J=8.4Hz,1H),7.39(d,J=7.2Hz,2H),7.33–7.18(m,4H),5.34(s,2H),2.45(s,3H). 13C{ 1 H}NMR(101MHz,CDCl3)δ167.4,138.3,135.6,133.5,132.4,131.2,130.5,12 8.7,128.5,128.4,128.1,127.6,127.5,125.0,122.0,67.6,22.1.IR(neat) :2960,2306,1720,1598,1548,1496,1452,1372,1299,1261,1230,1192,114 7,1121,962,898,838,800,745,696,663,638,615,589,531,499,481,416cm -1 HRMS (ESI) theoretical value C 19 H 16 O2Br[M+H] + :355.0328, Experimental value:355.0324.

[0331]

[0332] (1c) is obtained through method III. 1 H NMR (400MHz, CDCl3) δ8.48(d,J=9.2Hz,1H),7.98(d,J=8.8Hz,1H),7.69–7. 58(m,2H),7.58–7.48(m,3H),7.46–7.32(m,3H),5.45(s,2H),2.65(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ169.1,137.2,136.3,136.2,133.8,132.5,130.9,130.3,130.2,130.1,129.70 129.4,128.0,126.2,122.2,69.3,21.0.IR(neat):2950,1726,1600,1501,1445,1381 ,1338,1274,1221,1154,1129,1032,971,912,878,752,696,625,599,578,486,417cm -1 HRMS (DART) theoretical value C 19 H 16 O2Br[M+H] + 355.0334, Experimental value: 355.0325.

[0333]

[0334] (1d) was obtained through method III. 1 H NMR (400MHz, CDCl3) δ8.05(s,1H),7.86(d,J=8.4Hz,1H),7.58(d,J=8.8Hz,1H),7.45(d ,J=6.4Hz,2H),7.41–7.27(m,3H),7.21(s,1H),5.40(s,3H),2.59(s,3H),2.47(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ169.1,139.4,137.3,136.2,134.5,134.3,133.0, 132.7,130.3,130.1,130.1,127.5,126.3,125.4,124.2,69.2,23.7,21.1 .IR(neat):3645,2338,1711,1601,1499,1458,1366,1314,1268,1188,11 34,1070,1003,945,904,845,818,783,749,694,611,572,554,504,478cm -1 HRMS (DART) theoretical value C 20 H 18 O2Br[M+H] + :369.0485, Experimental value:369.0480.

[0335]

[0336] Obtained via method III (1e), 1 H NMR (400MHz, CDCl3) δ7.79–7.72(m,3H),7.61–7.50(m,3H),7.47–7.35(m,3H),7.30–7.24(m,1H),5.47(s,2H),4.01(s,3H). 13 C{ 1H}NMR (101MHz, CDCl3) δ167.4,159.5,135.6,133.7,131.6,130.7,129.8,128. 7,128.5,128.4,127.5,123.6,121.1(2C),106.6,67.6,55.5.IR(neat):3663,2 974,1727,1625,1597,1503,1453,1369,1298,1261,1219,1200,1121,1028,97 5,930,903,837,801,767,738,712,696,664,593,572,531,511,479,440,418cm -1 HRMS (DART) theoretical value C 19 H 16 O3Br[M+H] + :371.0277, Experimental value:371.0274.

[0337]

[0338] Obtained via method III (1f), 1 H NMR(400MHz, CDCl3)δ8.28(d,J=9.2Hz,1H),7.64–7.56(m,2H),7.41(d,J=6.8Hz,2H), 7.37–7.25(m,3H),7.21–7.16(m,1H),7.01(d,J=2.4Hz,1H),5.34(s,2H),3.85(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ167.1,159.4,137.0,135.7,130.5,128.6,128.5,12 8.4(2C),127.8,126.8,126.5,123.2,120.8,105.9,67.5,55.5.IR(neat):3 032,2338,1723,1619,1559,1495,1476,1454,1402,1370,1319,1272,1229, 1194,1170,1120,1029,981,852,820,790,772,742,696,677,602,533,497cm -1 HRMS (DART) theoretical value C 19 H 16 O3Br[M+H] + :371.0277, Experimental value:371.0274.

[0339]

[0340] (1 g)(1.29 g, 87%) was obtained by method III. 1 H NMR (400MHz, CDCl3) δ8.20(d,J=8.8Hz,1H),7.93(d,J=8.8Hz,1H),7.57(d,J=8.8Hz,1H) ,7.50–7.39(m,3H),7.37–7.23(m,3H),6.84(d,J=7.6Hz,1H),5.36(s,2H),3.92(s,3H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ167.4,155.2,135.5,133.3,131.9,128.6,128.5,128.4,128.1,127.5,124.9,122.0,120.5,105.9,67.6,55.9.IR(neat ):2960,1721,1591,1561,1494,1454,1409,1373,1308,1262,1232,1166 ,1128,1077,1000,955,885,827,799,752,698,653,607,570,550,489cm -1 HRMS (DART) theoretical value C 19 H 16 O3Br[M+H] + :371.0277, Experimental value:371.0274.

[0341]

[0342] (513 mg, 82%) was obtained via method III (1 h). 1 H NMR(400MHz, CDCl3) δ8.49(d,J=9.2Hz,1H),7.99(d,J=1.6Hz,1H),7.92–7.79 (m,2H),7.79–7.64(m,3H),7.55–7.46(m,4H),7.43–7.33(m,4H),5.44(s,2H). 13 C{ 1H}NMR(101MHz,CDCl3)δ167.1,140.8,139.8,135.6,135.6,131.6,130.8,129 .3,129.1,128.7,128.5(2C),128.1,128.0,127.8,127.5,126.4,125.8,122. 9,67.6.IR(neat):3655,2973,2319,1723,1592,1484,1459,1378,1323,1272 ,1226,1150,1125,1079,974,945,889,822,791,761,737,693,610,545,476cm -1 HRMS (DART) theoretical value C 24 H 18 O2Br[M+H] + :417.0485, Experimental value:417.0480.

[0343]

[0344] (1i) (478 mg, 75%) was obtained via method III. 1 H NMR (400MHz, CDCl3) δ8.34(d,J=9.6Hz,1H),7.66(dd,J=21.2,8.4Hz,2H),7.48(d,J=6.8Hz,2H),7.42–7.30(m,3H),7.25(dd,J=9.2,2.4H z,1H),7.06(d,J=2.4Hz,1H),5.93–5.80(m,1H),5.41(s,2H),5.15–4.96(m,2H),4.12–4.08(m,2H),2.32–2.21(m,2H),2.00–1.86(m,2H). 13 C{ 1H}NMR(101MHz,CDCl3)δ167.1,158.8,137.6,137.0,135.7,130.4,128.6,128.5,128.4,1 28.2,127.7,126.8,126.4,123.3,121.1,115.5,106.6,67.5,67.4,30.1,28.3.IR(neat): 3060,2939,2853,1726,1619,1495,1464,1426,1394,1369,1345,1326,1261,1233,1177,1 121,1080,1050,1019,961,903,852,820,797,746,728,695,643,604,546,514,485,413cm -1 HRMS (DART) theoretical value C 23 H 22 O3I[M+H] + :425.0747, Experimental value:425.0743.

[0345]

[0346] (2a) (1.2 g, 37%) was obtained by method I. 1 H NMR (400MHz, CDCl3) δ8.49 (d, J = 8.4Hz, 1H), 7.95–7.82 (m, 3H), 7.72–7.58 (m, 2H), 7.52–7.42 (m, 2H), 7.36–7.26 (m, 3H). 13 C NMR (101MHz, CDCl3) δ165.9,150.9,135.4,132.4,130.5,129.6,128.7,128.5,128.3(2C),128.1,126.2,126.0,123.5,121.6.

[0347]

[0348] (2b) (683 mg, 52.2%) was obtained by method I. 1 H NMR(400MHz, CDCl3) δ8.42(d,J=8.8Hz,1H),7.86(dd,J=20.4,8.4Hz,2H),7.66(s,1H ),7.59–7.42(m,3H),7.38–7.27(m,3H),2.87(q,J=7.6Hz,2H),1.36(t,J=7.6Hz,3H). 13 C{ 1H}NMR(101MHz, CDCl3)δ165.8,150.9,144.9,135.9,131.0,129.6,129.4,128.7,127.5,126.1,125.9,123.6,121.7,28.8 ,15.2.IR(neat):1748,1727,1622,1588,1483,1320,1272,1227,1183,1160,1099,970,892,827,747,712,690,497,416cm -1 HRMS (ESI) theoretical value C 19 H 16 O2Br[M+H] + :355.0328, Experimental value:355.0326.

[0349]

[0350] (2c)(1.6g, 80%) was obtained by method I. 1 H NMR (400MHz, CDCl3) δ8.57(d,J=8.8Hz,1H),8.08(s,1H),7.99–7.90(m,3H),7.76(d,J=8.0Hz,2H),7.58–7.40(m,5H),7.38–7.28(m,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ165.7,150.9,141.2,139.8,135.8,131.6,130.1,129.6,129.4,129.1,128.2,127.9,127.5,126.5,126.2 ,125.9,123.6,121.6.IR(neat):3066,1744,1721,1590,1486,1246,1188,1160,1094,982,925,899,827,751,710,687,587,517cm -1 HRMS (ESI) theoretical value C 23 H 16 O2Br[M+H] + :403.0328, Experimental value:403.0327.

[0351]

[0352] (2d)(1.03g, 72%) were obtained by method I. 1H NMR (400MHz, CDCl3) δ8.41(d,J=8.4Hz,1H),7.89(d,J=8.4Hz,1H),7.76(d,J =8.4Hz,1H),7.50–7.42(m,2H),7.35–7.27(m,4H),7.14(s,1H),3.96(s,3H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ165.7,159.6,150.9,137.2,130.6,129.6,127.9,127.6,127.0,126.6,126.1,123.9,121.7,121.0,106.0,55 .6.IR(neat):3054,1742,1591,1469,1372,1320,1266,1224,1185,1098,1025,967,929,854,766,741,716,687,612,515,494,418cm -1 HRMS (ESI) theoretical value C 18 H 14 O3Br[M+H] + :357.0121, Experimental value:357.0120.

[0353]

[0354] To a 250 mL round-bottom flask equipped with a stir bar, add 30 mmol of 6-hydroxy-4-hydronaphthone, 1.0 equiv, potassium carbonate (60 mmol, 2.0 equiv), 5-bromo-1-pentene (45 mmol, 1.5 equiv), and 50 mL of DMF. Heat the reaction mixture to 60 °C and monitor the reaction by thin-plate chromatography. After the reaction is complete, cool the reaction mixture, dilute it with ethyl acetate and water, separate the layers, wash the organic phase with saturated ammonium chloride water, separate the layers again, dry the organic phase with anhydrous magnesium sulfate, filter, and concentrate by rotary evaporation to obtain crude product S10. Using crude product S10 as a starting material, obtain 2e by method 1. 1 H NMR (400MHz, CDCl3) δ8.40(d,J=9.2Hz,1H),7.87(d,J=8.4Hz,1H),7.72(d,J=8.8Hz,1H),7.49–7.40(m,2H),7.34–7.26(m 4H),7.11(d,J=2.4Hz,1H),5.95–5.80(m,1H),5.14–4.98(m,2H),4.11(t,J=6.4Hz,2H),2.34–2.23(m,2H),2.01–1.90(m,2H)13 C{ 1 H}NMR(101MHz,CDCl3)δ165.7,159.1,150.9,137.6,137.3,130.6,129.5,12 7.6,127.5,126.9,126.6,126.1,124.0,121.7,121.24115.5,106.7,67.5,3 0.1,28.3.IR(neat):3072,1741,1616,1591,1490,1461,1370,1313,1267,1 221,1191,1102,1011,946,909,853,823,752,734,690,572,513,499,415cm -1 HRMS (DART) theoretical value C 22 H 20 O3Br[M+H] + :411.0590, Experimental value:411.0588.

[0355]

[0356] (2f)(1.2g, 83%) was obtained by method I. 1 H NMR (400MHz, CDCl3) δ8.25(s,1H),7.87–7.72(m,3H),7.50–7.40(m,3H),7.37–7.26(m,3H),2.58(s,3H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ166.0,150.9,138.5,133.7,132.5,130.7,130.5,129.6,128.2,127.7,127.6,126.2,125.1,122.6,121.6,22.1.IR( neat):1739,1591,1486,1455,1369,1302,1264,1232,1185,1159,1109,1003,970,942,908,842,741,689,661,575,534,516,500,482,422cm -1 HRMS (ESI) theoretical value C 18 H 14 O2Br[M+H]: 341.0172, experimental value: 341.0170.

[0357]

[0358] (2g)(1.8g, 70%) were obtained by method I. 1 H NMR (400MHz, CDCl3) δ8.12 (d, J = 11.2Hz, 1H), 7.92–7.77 (m, 3H), 7.55–7.26 (m, 6H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ165.6,163.4,161.0,150.8,133.7(d,J=9.1Hz),132.3,131.5 131.0(d,J=9.1Hz),129.7,127.9,126.3,125.3(d,J=2.5Hz),121.6,119.0(d,J=25.7Hz),112.6(d,J=24.4Hz) 19 F NMR(376MHz, CDCl3)δ-110.06.IR(neat):1748,1626,1592,1503,1450,1298, 1253,1225,1179,1152,1103,980,954,862,845,738,717,686,527,491,427cm -1 HRMS (ESI) theoretical value C 17 H 10 O2BrFNa[M+Na] + :366.9740, Experimental value:366.9740.

[0359]

[0360] Obtained via method I (2h) (412mg, 80%). 1 H NMR (400MHz, CDCl3) δ8.39(d,J=8.4Hz,1H),8.11(d,J=8.8Hz,1H),7.87(d,J=8.8Hz,1H),7.60–7.53(m,1H),7.50 –7.40(m,3H),7.37–7.26(m,3H),3.13–3.01(m,2H),1.78–1.67(m,2H),1.46–1.29(m,4H),0.91(t,J=6.8Hz,3H). 13 C{ 1H}NMR (101MHz, CDCl3) δ166.0,150.9,139.6,134.1,132.8,130.2,129.6,128.6,127. 9,127.1,126.2,125.5,124.1,124.0,121.6,33.2,31.9,30.7,22.6,14.1.IR(neat): 2955,2930,2852,1743,1591,1489,1458,1359,1327,1270,1253,1191,1159,1115,10 90,1023,939,909,839,822,805,791,753,733,686,638,584,558,527,508,480,425cm - 1 HRMS (ESI) theoretical value C 22 H 22 O2Br[M+H] + :397.0789, Experimental value:397.0787.

[0361]

[0362] (532 mg, 35%) was obtained by method I. 1 H NMR (400MHz, CDCl3) δ8.36(d,J=8.8Hz,1H),8.05(d,J=8.8Hz,1H),7.82(d,J=8.8Hz,1H),7 .60–7.52(m,1H),7.50–7.40(m,2H),7.36–7.26(m,3H),6.95(d,J=7.6Hz,1H),4.02(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ166.0,155.3,150.9,133.4,131.2,129.6,128.3,127.7,126.2,125.0,122.6,122.2,121.6,120.6,106. 1,55.9.IR(neat):1737,1591,1486,1457,1410,1365,1309,1260,1225,1187,1110,1000,928,905,836,798,758,690,601,495cm -1 HRMS (ESI) theoretical value C 18 H 14 O3Br[M+H] + :357.0121, Experimental value:357.0120.

[0363]

[0364] Obtained by method I (1.72 g, 68%). 1 H NMR (400MHz, CDCl3) δ8.49(d,J=8.4Hz,1H),7.96(d,J=8.4Hz,1H),7.73–7.55(m,3H),7.50–7.37(m,2H),7.36–7.23(m,3H),2.66(s,3H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ166.0,150.9,134.8,134.8,132.2,130.1,129.6,129.3,128.3,127.91,126.5,126.2,124.6,121.7,121.2,19.4.IR( neat):2963,1727,1594,1491,1444,1377,1344,1276,1231,1196,1159,1124,1071,955,917,872,834,742,719,686,627,560,505,485,419cm -1 HRMS (ESI) theoretical value C 18 H 14 O2Br[M+H] + :341.0172, Experimental value:341.0172.

[0365]

[0366] 2kJ (840 mg, 69%) was obtained by method II. 1 H NMR (400MHz, CDCl3) δ8.38(d,J=8.4Hz,1H),7.91–7.83(m,2H),7.71–7.41(m,7H),7.37–7.14(m,3H),6.81(d,J=8.0Hz,2H). 13 C{ 1H}NMR(101MHz,CDCl3)δ166.4,150.4,139.5,137.8,134.2,133.8,130.8,12 9.5,129.1,128.8,128.6,128.5,128.3(2C),128.2,127.7,126.2,121.4,12 0.7.IR(neat):3054,1744,1589,1484,1325,1251,1218,1188,1159,1096,1 024,978,923,900,846,770,742,720,701,687,647,608,581,546,504,481cm -1 HRMS (ESI) theoretical value C 23 H 19 O2NBr[M+NH4] + :420.0594, Experimental value:420.0594.

[0367]

[0368] 2l (834 mg, 65%) was obtained by method II. 1 H NMR(400MHz, CDCl3)δ8.37(d,J=8.0Hz,1H),7.92–7.82(m,2H),7.72–7.56(m,2H),7.49(d,J=8.0Hz,2H), 7.34–7.29(m,4H),7.23–7.16(m,1H),6.79(d,J=8.0Hz,2H),2.74(q,J=7.6Hz,2H),1.31(t,J=7.6Hz,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ166.5,150.4,144.5,137.9,136.8,134.2,134.0, 130.7,129.4,129.1,128.6,128.4,128.2,128.1,127.7,126.2,121.5,12 0.6,28.7,15.9.IR(neat):3065,1745,1589,1483,1442,1255,1217,1185 ,1158,1136,1116,1093,1020,980,924,896,844,745,689,620,583,496cm -1 HRMS (ESI) theoretical value C 25 H 19 O2BrNa[M+Na] +:453.0461, Experimental value:453.0462.

[0369]

[0370] 2m (792mg, 59%) was obtained by method I. 1 H NMR(400MHz, CDCl3)δ8.39(d,J=8.0Hz,1H),8.00–7.80(m,2H),7.75–7.58(m,2H),7.50(d,J=8.0Hz,2H), 7.40–7.15(m,5H),6.80(d,J=7.6Hz,2H),2.70(t,J=7.6Hz,2H),1.81–1.67(m,2H),1.02(t,J=7.2Hz,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ166.5,150.4,142.8,137.9,136.8,134.2,133.9,130.7 ,129.4,129.0,128.7(2C),128.4,128.2,128.1,127.7,126.2,121.5,120.6,37. 8,24.7,13.8.IR(neat):2952,2864,1753,1590,1484,1326,1253,1216,1184,1 159,1134,1091,1022,980,923,896,824,771,743,690,610,581,540,500,460cm -1 HRMS (ESI) theoretical value C 26 H 22 O2Br[M+H] + :445.0798, Experimental value:445.0796.

[0371]

[0372] 2n (757 mg, 57%) was obtained by method II. 1 H NMR (400MHz, CDCl3) δ8.37(d,J=8.0Hz,1H),7.90–7.86(m,2H),7.71–7.58(m,2H),7.49(d,J=8 .0Hz,2H),7.38–7.15(m,5H),6.72(d,J=7.6Hz,2H),3.08–2.94(m,1H),1.33(d,J=6.9Hz,6H). 13 C{ 1H}NMR (101MHz, CDCl3) δ166.5,150.4,149.0,137.9,137.0,134.2,134.0,130.7 ,129.4,129.1,128.6,128.4,128.2,128.2,127.7,126.7,126.2,121.5,120.5,3 4.0,24.1.IR(neat):3066,2956,1744,1589,1482,1251,1217,1186,1160,1136 ,1095,1018,982,927,896,847,826,770,741,709,691,618,586,545,518,462cm -1 HRMS (ESI) theoretical value C 26 H 22 O2Br[M+H] + :445.0798, Experimental value:445.0798.

[0373]

[0374] 2o (1.12 g, 82%) was obtained by method II. 1 H NMR (400MHz, CDCl3) δ8.38 (d, J = 8.4Hz, 1H), 7.88 (s, 2H), 7.70–7.58 (m, 2H), 7.52–7. 47(m,4H),7.32–7.26(m,2H),7.22–7.15(m,1H),6.68(d,J=8.0Hz,2H),1.40(s,9H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ166.5,151.3,150.4,137.9,136.6,134.2,134.0 ,130.7,129.3,128.8,128.5,128.4,128.2,128.2,127.7,126.2,125.5, 121.5,120.5,34.7,31.4.IR(neat):3064,1740,1590,1484,1363,1253, 1220,1187,1159,1111,1002,927,897,842,747,690,612,586,518,465cm -1 HRMS (ESI) theoretical value C 27 H 24 O2Br[M+H] + :459.0954, Experimental value:459.0956.

[0375]

[0376] 2p (879mg, 68%) was obtained via method II (the yield of the last step). 1 H NMR (400MHz, CDCl3) δ8.37(d,J=8.4Hz,1H),7.94–7.80(m,2H),7.72–7.57(m,2H),7.51(d,J=8 .8Hz,2H),7.43–7.30(m,2H),7.25–7.19(m,1H),7.02(d,J=8.8Hz,2H),6.90(d,J=7.6Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ166.6,159.7,150.4,137.5,134.2,134.0,131.8,1 30.6,130.3,129.5,128.7,128.4,128.2,128.1,127.6,126.2,121.5,120.6 ,114.1,55.5.IR(neat):3057,1742,1591,1514,1485,1459,1290,1257,12 24,1177,1159,1088,1025,923,891,848,826,743,687,619,541,517,497cm -1 HRMS (ESI) theoretical value C 24 H 17 O3BrNa[M+Na] + :455.0253, Experimental value:455.0255.

[0377]

[0378] 2q (723 mg, 51%) was obtained by method II. 1 H NMR (400MHz, CDCl3) δ8.40 (d, J = 8.4Hz, 1H), 8.02–7.84 (m, 2H), 7.79–7.61 (m, 8H), 7.55–7. 45(m,2H),7.44–7.36(m,1H),7.35–7.26(m,2H),7.24–7.15(m,1H),6.86(d,J=8.4Hz,2H). 13 C{ 1H}NMR (101MHz, CDCl3) δ166.5,150.4,141.1,140.6,138.4,137.4,134.2,133.8,130. 8,129.5,129.5,129.0,128.7,128.5,128.3(2C),127.7(2C),127.4,127.2,126.3,121 .4,120.8.IR(neat):2920,1737,1590,1554,1483,1438,1438,1322,1261,1229,1181 ,1155,1123,1090,980,920,899,852,824,762,737,691,610,580,553,515,498,475cm -1 HRMS (DART) theoretical value C 29 H 20 O2Br[M+H] + :479.0641, Experimental value:479.0642.

[0379]

[0380] 2r (957 mg, 76%) was obtained by method II. 1 H NMR (400MHz, CDCl3) δ8.38 (d, J = 8.4Hz, 1H), 7.93–7.81 (m, 2H), 7.76–7.50 (m, 4H), 7.42–7.12 (m, 5H), 6.87 (d, J = 7.6Hz, 2H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ166.3,162.9(d,J=248.5Hz),150.3,136.6,135.4(d,J=4.0Hz),134.1,1 33.8,130.9,130.8,129.6,128.8,128.4(2C),127.7,126.3,121.3,120.8,115.6(d,J=21.2Hz). 19 F NMR(376MHz, CDCl3)δ-113.69.IR(neat):3064,1742,1590,1485,1324,1253, 1218,1188,1159,1096,982,923,890,823,740,710,687,619,578,519,493cm -1 HRMS (ESI) theoretical value C 23 H 15 O2BrF[M+H]+ :421.0234, Experimental value:421.0227.

[0381]

[0382] 2s (851 mg, 65%) were obtained by method II. 1 H NMR(400MHz, CDCl3)δ8.37(d,J=8.4Hz,1H),7.93–7.80(m,2H),7.75–7.60(m,2H) ,7.56–7.44(m,4H),7.40–7.31(m,2H),7.27–7.19(m,1H),6.88(d,J=7.6Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ166.2,150.3,137.9,136.4,134.5,134.1,133.5,1 30.9,130.4,129.6,128.8,128.8,128.5,128.5,128.4,127.7,126.4,121.3 ,120.9.IR(neat):1746,1591,1488,1441,1259,1222,1188,1159,1132,107 9,1013,976,920,900,846,818,771,731,688,610,578,542,515,481,446cm -1 HRMS (DART) theoretical value C 23 H 15 O2BrCl[M+H] + :436.9938, Experimental value:436.9939.

[0383]

[0384] 2t (742mg, 56%) was obtained by method II. 1 H NMR (400MHz, CDCl3) δ8.40 (d, J = 8.4Hz, 1H), 8.14–8.02 (m, 2H), 7.97–7.84 (m, 2H), 7. 78–7.61(m,4H),7.39–7.29(m,2H),7.25–7.19(m,1H)6.92–6.83(m,2H),2.67(s,3H). 13 C{ 1H}NMR(101MHz,CDCl3)δ197.6,166.1,150.3,144.1,136.6,136.5,134.0,133.3,1 31.1,129.6,129.3,128.9,128.7,128.6(2C),128.5,127.7,126.4,121.2(2C),26. 8.IR(neat):2987,1745,1683,1590,1484,1435,1403,1356,1256,1222,1182,115 8,1092,1070,1015,957,920,892,852,825,735,685,599,579,541,516,500,483cm -1 HRMS (ESI) theoretical value C 25 H 18 O3Br[M+H] + :445.0439, Experimental value:445.0430.

[0385]

[0386] 2u (952mg, 73%) was obtained by method II. 1 H NMR(400MHz, CDCl3)δ8.40(d,J=8.4Hz,1H),8.17(d,J=8.4Hz,2H),7.95–7.85(m,2H),7 .75–7.60(m,4H),7.38–7.30(m,2H),7.25–7.19(m,1H),6.92–6.84(m,2H),3.97(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ166.8,166.1,150.3,144.0,136.6,134.1,133.3 ,131.0,129.9,129.6,129.1,128.9,128.7,128.6,128.5,127.7,126.3,1 21.2,121.1,52.3.IR(neat):3059,2916,2853,1739,1591,1487,1431,13 74,1263,1224,1188,1159,1105,1021,974,921,896,828,742,688,503cm -1 HRMS (ESI) theoretical value C 25 H 18 O4Br[M+H] + :461.0383, Experimental value:461.0384.

[0387]

[0388] 2v (812mg, 58%) was obtained by method II. 1 H NMR (400MHz, CDCl3) δ8.39(d,J=8.4Hz,1H),7.94–7.83(m,2H),7.81–7.61(m,6H),7.33(t,J=7.8Hz,2H),7.28–7.18(m,1H),6.79(d,J=8.4Hz,2H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ166.1,150.2,143.0,136.2,134.0,133.3,131.1,130.4(q,J=33.3Hz),129.5( 2C),128.8,128.7,128.6,128.5,127.7,126.4,125.5(q,J=4.0Hz),124.1(q,J=272.7Hz),121.1(2C). 19 F NMR(376MHz, CDCl3)δ-62.56.IR(neat):3066,1740,1590,1484,1444,1321,1252,1219,11 82,1161,1124,1098,1065,1017,984,926,897,851,828,768,746,720,689,613,587,518cm -1 HRMS (DART) theoretical value C 24 H 15 O2BrF3[M+H] + :471.0202, Experimental value:471.0199.

[0389]

[0390] Two weeks (723 mg, 51%) were obtained using method II. 1 H NMR (400MHz, CDCl3) δ8.41(d,J=8.4Hz,1H),8.02–7.86(m,2H),7.83(s,1H),7.77–7.51(m,7H),7.50–7.13(m,6H),6.81(d,J=8.4Hz,2H). 13 C{ 1H}NMR (101MHz, CDCl3) δ166.5,150.4,141.6,140.6,139.9,137.7,134.2,133.8,13 0.9,129.5,129.1,128.9,128.8,128.5,128.4,128.3,128.0,127.9,127.7,127.6,1 27.3,126.9,126.2,121.4,120.8.IR(neat):3052,1744,1590,1484,1260,1219,11 82,1157,1130,1096,984,901,855,835,765,737,703,685,579,560,520,495,468cm -1 HRMS (DART) theoretical value C 29 H 20 O2Br[M+H] + :479.0641, Experimental value:479.0645.

[0391]

[0392] Two doses (852 mg, 66%) were obtained using method II. 1 H NMR(400MHz, CDCl3)δ8.37(d,J=8.4Hz,1H),7.92–7.83(m,2H),7.73–7.57(m,2H),7.45 –7.30(m,3H),7.25–7.10(m,3H),7.05–6.97(m,1H),6.88(d,J=7.6Hz,2H),3.82(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ166.4,159.7,150.5,140.8,137.7,134.2,133.7,130.8,129 .7,129.5,128.7,128.5,128.3(2C),127.7,126.2,121.5,121.5,120.8,114.5,114. 1,55.4.IR(neat):1744,1578,1488,1452,1325,1284,1258,1233,1177,1157,1132, 1082,1047,987,923,905,873,825,801,772,735,719,686,625,567,516,498,472cm -1 HRMS (DART) theoretical value C 24 H 18O3Br[M+H] + :433.0434, Experimental value:433.0433.

[0393]

[0394] Two days (945 mg, 72%) were obtained by method II. 1 H NMR (400MHz, CDCl3) δ8.39 (d, J = 8.0 Hz, 1H), 7.92–7.82 (m, 2H), 7.76–7.60 (m, 2H), 7.39 (t, J = 8. 0Hz,2H),7.28–7.22(m,1H),7.15(d,J=6.0Hz,2H),7.01(d,J=8.0Hz,2H),6.92(t,J=8.8Hz,1H). 13 C{ 1 H}NMR(101MHz, CDCl3)166.0,164.1(d,J=13.1Hz),161.7(d,J=13.1Hz),150.3,142.5(t,J=10.1Hz),135.3(t,J=2.5Hz),13 4.0,133.1,131.2,130.0,128.9,128.8,128.6(2C),127.7,126.5,121.2,112.3(dd,J=26.3Hz,11.Hz),103.7(t,J=25.3Hz). 19 F NMR(376MHz, CDCl3)δ-108.81.IR(neat):3067,1744,1620,1589,1486,1451,1340, 1258,1216,1186,1092,1020,983,884,867,844,771,739,684,619,574,506,470cm -1 HRMS (DART) theoretical value C 23 H 14 O2BrF2[M+H] + :439.0140, Experimental value:439.0139.

[0395]

[0396] 2z (948 mg, 70%) was obtained by method II. 1H NMR(400MHz, CDCl3)δ8.40(d,J=8.4Hz,1H),8.06(s,1H),7.98–7.85(m,5H),7.74–7.6 0(m,3H),7.57–7.49(m,2H),7.27–7.19(m,2H),7.17–7.10(m,1H),6.84–6.77(m,2H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ166.5,150.4,137.7,136.8,134.2,133.9,133.2,132.9 ,130.8,129.4,129.1,128.5,128.4(2C),128.3(2C),128.2,127.8,127.7,126.9 ,126.7,126.6,126.2,121.4,120.9.IR(neat):3050,2389,1744,1588,1483,144 4,1254,1215,1182,1157,1088,991,927,908,890,820,743,692,582,516,477cm -1 HRMS (DART) theoretical value C 27 H 18 O2Br[M+H] + :453.0485, Experimental value:453.0476.

[0397]

[0398] 2ab (892 mg, 73%) was obtained by method II. 1 H NMR(400MHz, CDCl3)δ8.31(d,J=8.4Hz,1H),7.81(d,J=7.6Hz,1H),7.71(s,1H),7.65–7.54(m,2H),7.50–7 .40(m,2H),7.30–7.25(m,3H),6.09–5.69(m,1H),2.53–2.34(m,2H),2.30–2.18(m,2H),1.87–1.66(m,4H). 13 C{ 1H}NMR (101MHz, CDCl3) δ166.6,150.8,140.2,136.8,134.2,133.7,130.5,129.6, 128.7,128.2,127.9,127.8,127.5,126.8,126.2,121.5,120.2,30.4,25.6,23.1, 21.8.IR(neat):2919,1733,1590,1554,1485,1437,1321,1259,1235,1211,1175, 1153,1122,1075,1045,979,953,922,884,820,739,691,612,579,548,498,472cm -1 HRMS (ESI) theoretical value C 23 H 20 O2Br[M+H] + :407.9641, Experimental value:407.0641.

[0399]

[0400] 2ab (1.42 g, 73%) was obtained by method I. 1 H NMR (400MHz, CDCl3) δ9.03(d,J=4.0Hz,1H),8.82(d,J=8.4Hz,1H),8.18(q,J=8.8Hz,2H),7.64–7.58(m,1H),7.52–7.41(m,2H),7.37–7.28(m,3H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ165.1,152.6,150.7,149.5,137.1,130.9,129.7,129.5,128.3,126.4,123.1,123.1,121.6,121.5.IR(neat):2987,1747,1 586,1552,1484,1452,1409,1325,1258,1223,1177,1163,1112,1036,101 8,968,927,900,845,810,793,752,691,667,616,569,537,511,488,461cm -1 HRMS (DART) theoretical value C 23 H 20 O2Br[M+H] + :327.9968, Experimental value:327.9964

[0401]

[0402] To a 250 mL round-bottom flask equipped with a stir bar, add 2-naphthol (50 mmol, 1.0 equiv), acetonitrile (100 mL), N-iodosuccinimide (60 mmol, 1.2 equiv), and p-toluenesulfonic acid (50 mmol, 1.0 equiv). Stir the reaction mixture at room temperature for 4 h. After the reaction is complete, quench the reaction with saturated sodium bisulfite solution, separate the phases, and extract the aqueous phase with dichloromethane. Combine the organic phases, dry them with anhydrous magnesium sulfate, filter, and remove the solvent from the filtrate by rotary evaporation to obtain the crude product 1-iodo-2-naphthol. To a dry 250 mL round-bottom flask equipped with a stir bar, add the crude 1-iodo-2-naphthol, potassium carbonate (100 mmol, 2.0 equiv), benzyl bromide (62.5 mmol, 1.25 equiv), and DMF (100 mL). Heat the reaction mixture to 70 °C and monitor the reaction by thin-plate chromatography. After the reaction was complete, the reaction mixture was diluted with water and ethyl acetate, separated, and the organic phase was dried over anhydrous magnesium sulfate. The mixture was filtered, and the solvent was removed from the filtrate by rotary evaporation. The concentrated solution was purified by rapid column chromatography to give substrate 6a (15.2 g, 84%). 1 H NMR (400MHz, CDCl3) δ8.17(d,J=8.4Hz,1H),7.85–7.67(m,2H),7.65–7.50(m,3H),7.46–7.31(m,4H),7.20(d,J=8.8Hz,1H),5.30(s,2H).

[0403]

[0404] 6-Cyclopropyl-1-bromo-2-benzyloxynaphthalene (3.9 mmol, 1.0 quiv) and THF (20 mL) were added to a 100 mL three-necked flask equipped with a stirrer. After purging with nitrogen, the mixture was stirred at -78 °C, followed by the addition of n-butyllithium (4.7 mmol, 1.2 equiv). The reaction mixture was stirred at -78 °C for 1 h, followed by the addition of iodine (7.8 mmol, 2.0 equiv). The reaction mixture was allowed to react at room temperature for 3 h. After the reaction was complete, the reaction was quenched with saturated sodium thiosulfate solution, and the mixture was separated. The aqueous phase was extracted with ethyl acetate (3 × 100 mL). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated by rotary evaporation. The concentrate was purified by rapid column chromatography to obtain product 6b (921 mg, 59%). 1H NMR (400MHz, CDCl3) δ8.03(d,J=8.8Hz,1H),7.64(d,J=8.8Hz,1H),7.53(d,J=7.2Hz,2H),7.45–7.27(m,4H),7 .26–7.20(m,1H),7.13(d,J=8.8Hz,1H),5.24(s,2H),2.09–1.94(m,1H),1.04–0.94(m,2H),0.81–0.73(m,2H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ155.2,140.2,136.8,134.1,131.4,130.2,129.5,12 8.6,128.0,127.3,126.9,124.1,115.0,89.0,72.0,15.2,9.2.IR(neat):302 9,2106,1808,1594,1495,1450,1380,1350,1319,1233,1164,1138,1079,10 44,1015,967,942,897,855,810,759,733,693,663,638,533,508,467,414cm -1 HRMS (DART) theoretical value C 20 H 17 OI[M+H] + :400.0319, Experimental value:400.0316.

[0405]

[0406] 6-Cyclohexyl-1-bromo-2-benzyloxynaphthalene (4.0 mmol, 1.0 quiv) and THF (20 mL) were added to a 100 mL three-necked flask equipped with a stirrer. After purging with nitrogen, the mixture was stirred at -78 °C, followed by the addition of n-butyllithium (4.8 mmol, 1.2 equiv). The reaction mixture was stirred at -78 °C for 1 h, followed by the addition of iodine (8.0 mmol, 2.0 equiv). The reaction mixture was allowed to react at room temperature for 3 h. After the reaction was complete, the reaction was quenched with saturated sodium thiosulfate solution. The mixture was separated, and the aqueous phase was extracted with ethyl acetate (3 × 100 mL). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated by rotary evaporation. The concentrate was purified by rapid column chromatography to obtain product 6c (922 mg, 52%). 1H NMR (400MHz, CDCl3) δ8.07(d,J=8.8Hz,1H),7.69(d,J=8.8Hz,1H),7.56–7.47(m,3H),7.45–7.27(m,4 H),7.15(d,J=9.2Hz,1H),5.27(s,2H),2.64(t,J=11.2Hz,1H),2.05–1.68(m,5H),1.62–1.21(m,5H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ155.3,144.3,136.8,134.3,131.2,130.3,129.9,128.6,128.4,128. 0,127.3,124.8,114.9,89.0,72.0,44.2,34.4,26.9,26.2.IR(neat):3668,3023,2927,2851, 2319,2123,1806,1593,1492,1448,1376,1335,1305,1262,1240,1204,1175,1139,1084,1062 ,1026,971,938,897,867,846,819,791,772,758,725,692,667,651,609,547,515,465,413cm -1 HRMS (DART) theoretical value C 23 H 23 OI[M+H] + :443.0872, Experimental value:443.0863.

[0407]

[0408] A stir bar was added to a dry 500 mL round-bottom flask equipped with a stirrer. 6-Aldehyde-2-benzyloxynaphthalene (76 mmol, 1.0 equiv), DMF (100 mL), MeCN (100 mL), and p-toluenesulfonic acid (76 mmol, 1.0 equiv) were then added to the reaction mixture at 0 °C. After the addition was complete, the reaction mixture was allowed to react overnight at room temperature. The reaction solution was quenched with saturated sodium thiosulfate solution, diluted with dichloromethane, and separated. The organic phase was washed with saturated ammonium chloride solution. The combined organic phases were dried over anhydrous magnesium sulfate, filtered, and concentrated by rotary evaporation to obtain S11 (13.5 g, 34%).

[0409] S11 (15 mmol, 1.0 equiv) and ethanol (100 mL) were added to a dry, stirrer-equipped round-bottom flask and stirred in an ice bath. Sodium borohydride (30 mmol, 2.4 equiv) was added to the reaction mixture at 0 °C, and the mixture was allowed to react overnight at room temperature. After the reaction was complete, the reaction was quenched with saturated ammonium chloride solution, and the ethanol was removed by rotary evaporation. The ethanol-free mixture was extracted with dichloromethane, separated, and the organic phases were combined. The organic phases were dried over anhydrous magnesium sulfate, and the filtrate was evaporated by rotary evaporation to remove the solvent, yielding crude product S12.

[0410] Add S12, dichloromethane (100 mL), and pyridine (30 mmol, 2.0 equiv) to a dry 250 mL round-bottom flask equipped with a stir bar. Then add acetic anhydride (22.5 mmol, 1.5 equiv) at 0 °C. Stir the reaction mixture overnight at room temperature. After the reaction is complete, remove the solvent from the mixture by rotary evaporation. Purify the concentrate by rapid column chromatography to give product 6d (3.9 g, 60%). White solid, mp = 79.5–80.7 °C. 1 H NMR(400MHz, CDCl3)δ8.17(d,J=8.4Hz,1H),7.82–7.67(m,2H),7.61–7.47(m,3H) ,7.46–7.30(m,3H),7.22(d,J=8.8Hz,1H),5.31(s,2H),5.26(s,2H),2.13(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ170.9,156.2,136.5,135.5,132.1,131.9,130.3,129.7, 128.6,128.2,128.0,127.7,127.23,115.0,88.8,71.9,66.0,21.1.IR(neat):29 60,1729,1630,1593,1494,1458,1377,1330,1259,1216,1167,1081,1035,959,9 28,892,867,843,814,799,779,753,720,699,645,611,541,517,493,468,441cm -1 HRMS (DART) theoretical value C 20 H 17 O3I[M+H] + :432.0217, Experimental value:432.0212.

[0411]

[0412] In a dry 250 mL round-bottom flask equipped with a stirrer, 20 mmol of methyltriphenylphosphine bromide (2.0 equiv) and 100 mL of tetrahydrofuran were added. Potassium tert-butoxide (15 mmol, 1.5 equiv) was added with stirring at 0 °C, and stirring was continued for 15 min. After 15 min, S11 (10 mmol, 1.0 equiv) was added. After the addition was complete, the reaction mixture was allowed to react at room temperature for 4 h. After the reaction was complete, the reaction was quenched with water, and the mixture was separated. The aqueous phase was extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated to remove the solvent, and the concentrated solution was separated by rapid column chromatography to give product 6e (1.73 g, 45%). White solid, mp = 118.4–119.7 °C. 1 H NMR(400MHz, CDCl3)δ8.08(d,J=8.8Hz,1H),7.74–7.47(m,5H),7.43–7.28(m,3H),7.12(d,J=8.8H z,1H),6.83(dd,J=17.6,10.8Hz,1H),5.83(d,J=17.6Hz,1H),5.31(d,J=10.8Hz,1H),5.24(s,2H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ155.9,136.6,136.3,135.5,133.8,131.6,130.4,13 0.1,128.6,128.0,127.2,126.5,125.5,114.9,114.3,88.9,71.9.IR(neat) :3660,2985,2319,1816,1587,1493,1448,1384,1334,1264,1227,1171,113 3,1078,1051,983,904,884,819,791,760,734,692,642,532,505,467,413cm -1 HRMS (DART) theoretical value C 19 H 16 OI[M+H] + :387.0240, Experimental value:387.0237.

[0413]

[0414] 6-Methoxy-1-bromo-2-benzyloxynaphthalene (5 mmol, 1.0 equiv) and THF (20 mL) were added to a 100 mL three-necked flask equipped with a stirrer. After purging with nitrogen, the mixture was stirred at -78 °C, followed by the addition of n-butyllithium (6 mmol, 1.2 equiv). The reaction mixture was stirred at -78 °C for 1 h, followed by the addition of iodine (10 mmol, 2.0 equiv). The reaction mixture was allowed to react at room temperature for 3 h. After the reaction was complete, the reaction was quenched with saturated sodium thiosulfate solution. The mixture was separated, and the aqueous phase was extracted with ethyl acetate (3 × 100 mL). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated by rotary evaporation. The concentrate was purified by rapid column chromatography to obtain product 6f (903 mg, 47%). Yellow solid, mp = 123.6–125.5 °C. 1 H NMR (400MHz, CDCl3) δ8.07(d,J=9.2Hz,1H),7.64(d,J=8.9Hz,1H),7.55(d,J=7.5Hz,2H) ,7.44–7.28(m,3H),7.26–7.10(m,3H),7.04(d,J=2.2Hz,1H),5.24(s,2H),3.90(s,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ156.7,154.4,136.8,133.0,131.1,130.9,128.8,128. 6,128.0,127.3,120.7,115.5,106.0,89.3,72.2,55.5.IR(neat):3654,2319, 1812,1626,1595,1496,1452,1370,1344,1248,1228,1195,1167,1124,1080,1 059,1025,970,937,877,845,813,792,732,693,646,575,548,506,464,415cm -1 HRMS (DART) theoretical value C 18 H 16 O2I[M+H] + :391.0189, Experimental value:391.0185.

[0415]

[0416] To a dry, stirrered 500 mL single-necked flask, add 20 mmol of 6-oxobenzyl-2-naphthoonitrile (1.0 equiv), 50 mL of DMF, 50 mL of acetonitrile, and 20 mmol of p-toluenesulfonic acid (1.0 equiv). Then, add 22 mmol of N-iodosuccinimide (1.1 equiv) at 0 °C. After the addition is complete, allow the reaction mixture to react overnight at room temperature. After the reaction is complete, quench the reaction with saturated sodium thiosulfate solution, dilute the reaction mixture with dichloromethane, separate the layers, and wash the organic phase with saturated ammonium chloride water. Dry the organic phase with anhydrous magnesium sulfate, filter, and concentrate the filtrate by rotary evaporation to obtain the crude product S11.

[0417] To a dry 250 mL round-bottom flask equipped with a stirrer, add crude product S11, sodium hydroxide (80 mmol, 4.0 equiv), water (50 mL), methanol (50 mL), and tetrahydrofuran (50 mL). Heat the reaction mixture to reflux for 48 h. After stopping the reaction, cool to room temperature and remove methanol and tetrahydrofuran by rotary evaporation. Adjust the pH of the remaining mixture to 1 with dilute hydrochloric acid, extract with ethyl acetate, combine the organic phases, dry them with anhydrous magnesium sulfate, and remove the solvent from the filtrate by rotary evaporation to obtain crude product S12 for the next step.

[0418] Crude product S11, potassium carbonate (40 mmol, 2.0 equiv), DMF (50 mL), and methyl iodoform (30 mmol, 1.5 equiv) were added to a dry 250 mL round-bottom flask equipped with a stirrer. The mixture was heated to 50 °C and reacted for 3 h. After the reaction was complete, ethyl acetate (500 mL) and water (200 mL) were added to the mixture, and the mixture was separated. The aqueous phase was treated with ethyl acetate (3 × 100 mL). The organic phases were combined, washed with saturated ammonium chloride water, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated by rotary evaporation. The concentrate was purified by rapid column chromatography to give 6 g (3.72 g, 44%) of the product. 1 H NMR (400MHz, CDCl3) δ8.47(s,1H),8.18(d,J=9.2Hz,1H),8.08(d,J=9.2Hz,1H),7.87(d,J=8.8Hz ,1H),7.54(d,J=7.6Hz,2H),7.45–7.30(m,3H),7.24(d,J=8.8Hz,1H),5.33(s,2H),3.97(s,3H). 13 C{ 1H}NMR(101MHz,CDCl3)δ167.0,157.6,138.1,136.3,131.8,131.6,131.3,128 .9,128.7,128.1,127.4,127.1,126.0,114.9,88.4,71.7,52.3.IR(neat):294 3,1693,1620,1594,1495,1472,1428,1397,1343,1327,1284,1266,1237,119 7,1135,1104,1043,981,912,865,844,794,766,733,696,630,552,497,415cm -1 HRMS (DART) theoretical value C 19 H 16 O3I[M+H] + :419.0139, Experimental value:419.0134.

[0419] Example 52 General steps for ligand synthesis

[0420]

[0421] A stir bar was added to a 250 mL single-necked flask, followed by 5-2 af (50 mmol, 1.0 equiv.) and 200 mL of dichloromethane. Then, m-chloroperoxybenzoic acid (60 mmol, 1.2 equiv.) was added at 0 °C. After the addition was complete, the mixture was allowed to react at room temperature for 12 hours. After the reaction was complete, the reaction was quenched with saturated sodium sulfite solution, and saturated potassium carbonate solution was added until alkaline. The mixture was separated, and the aqueous phase was extracted three times with dichloromethane. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by rotary evaporation to obtain crude product 5-2 ag.

[0422] A stir bar was added to a 500 mL single-necked flask, followed by 5-2 ag of crude product, dichloromethane (200 mL), trimethylcyanosilane (62.5 mmol, 1.25 equiv.), and dimethylcarbamoyl chloride (62.5 mmol, 1.25 equiv.). The mixture was reacted at room temperature for 24 hours after addition. After the reaction was complete, the reaction was quenched with saturated potassium carbonate solution (added slowly). The mixture was separated into liquid and aqueous phases, extracted three times with dichloromethane, and the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by rotary evaporation. The product 5-2 ah was then purified by rapid column chromatography.

[0423] A stir bar was added to a 250 mL single-necked flask, followed by the addition of 5-2aH (20 mmol, 1.0 equiv.), methanol (50 mL), and sodium methoxide (4 mmol, 20 mol%). The mixture was stirred at room temperature and the reaction was monitored by TLC. After the reaction was complete, methanol was removed by rotary evaporation, and the product was dissolved in ethyl acetate. The sodium methoxide was removed by filtration through a silica gel filter on a sintered glass core funnel. The solvent in the filtrate was removed by rotary evaporation to obtain crude 5-2aH for later use.

[0424] A stir bar was added to a 100 mL single-necked flask, followed by 5-2 mg of crude product, p-toluenesulfonic acid (4 mmol, 20 mol%), toluene (50 mL), and the corresponding amino alcohol (30 mmol, 1.5 μg eqiv.). After the addition was complete, the mixture was refluxed, and the reaction was monitored by TLC until the substrate was completely reacted. After the reaction was complete, the reaction solution was brought to room temperature, and the solution was directly purified by rapid column chromatography to obtain the product, pyridine oxazoline ligand.

[0425]

[0426] Ligand L8 was synthesized from 2-butylpyridine and (1S,2R)-aminoindanol via a standard procedure. It was a white solid, 4.6 g in weight, with a yield of 44% from the last two steps. 1 H NMR (400MHz, CDCl3) δ7.84(d,J=7.6Hz,1H),7.66–7.55(m,2H),7.29–7.23(m,3H),7.20(d,J=8.0Hz,1H),5.78(d,J=8.0Hz, 1H),5.63–5.50(m,1H),3.55–3.41(m,2H),2.92–2.71(m,2H),1.72–1.58(m,2H),1.41–1.30(m,2H),0.92(t,J=8.0Hz,3H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ163.5,162.9,146.4,141.7,139.9,136.6,128.5,127.4,125.8,125.3,124.5,121.6,83.9,77.0,39.9,38.3,32.3,2 2.6,14.0.IR(neat):2927,1626,1572,1459,1365,1292,1236,1161,1121,1088,1062,1021,996,851,810,743,672,648,621,543,452,430cm -1 HRMS (ESI) theoretical value C 19 H 21 N₂O[M+H] +:293.1648, experimental value:293.1654.[α] 29.8 = -192.86 (c = 1.0, CHCl3).

[0427]

[0428] Ligand L9 was synthesized from 2-pentylpyridine and (1S,2R)-aminoindanol via a standard procedure. It was a white solid, 2.5 g in weight, with a yield of 40% in the last two steps. 1 H NMR (400MHz, CDCl3) δ7.85(d,J=7.6Hz,1H),7.65–7.55(m,2H),7.30–7.23(m,3H),7.21(d,J=7.6Hz,1H),5.78(d,J=8.0Hz ,1H),5.62–5.53(m,1H),3.57–3.39(m,2H),2.90–2.75(m,2H),1.77–1.58(m,2H),1.9–1.22(m,4H),0.88(t,J=8.0Hz,3H). 13 C{ 1 H}NMR(101MHz,CDCl3)δ163.5,163.0,146.4,141.7,139.9,136.6,128.5 ,127.4,125.8,125.3,124.5,121.6,83.9,77.0,39.9,38.5,31.6,29.9, 22.6,14.0.IR(neat):2949,2926,2854,1627,1573,1460,1364,1291,12 33,1160,1121,1088,1065,1022,996,856,810,744,672,648,623,454cm -1 HRMS (ESI) theoretical value C 20 H 23 N₂O[M+H] + :307.1805, Experimental value:307.1808.[α] 28.8 = -197.69 (c = 1.0, CHCl3).

[0429]

[0430] Ligand L17 was synthesized from 2-hexylpyridine and (1S,2R)-aminoindanol via a standard procedure. It was a white solid, 7.4 g, with a yield of 38% in the last two steps. 1H NMR(400MHz, CDCl3) δ7.84(d,J=7.8Hz,1H),7.67–7.54(m,2H),7.32–7.16(m,4H),5.78(d,J=8.0Hz,1H),5.62–5.5 2(m,1H),3.58–3.38(m,2H),2.94–2.75(m,2H),1.75–1.60(m,2H),1.41–1.17(m,6H),0.92–0.87(t,J=5.2Hz,3H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ163.5,163.0,146.4,141.7,139.9,136.6,128.5,127.4,125.8,125.3,124.5,121.6,83.9,77. 0,39.9,38.6,31.7,30.2,29.1,22.6,14.1.IR(neat):2925,2852,1628,1574,1460,1429,1365,1295,1232,1162,1122 1089,1022,996,858,811,745,673,648,623,595,543,452,430cm -1 HRMS (ESI) theoretical value C 21 H 25 N₂O[M+H] + :321.1961, Experimental value: 321.1964. [α] 26.5 = -192.88 (c = 1.0, CHCl3).

[0431]

[0432] Ligand L14 was synthesized from 2-isopropylpyridine and (1S,2R)-aminoindanol via a standard procedure. 4.8 g was obtained, with a yield of 51% in the last two steps. 1 H NMR (400MHz, CDCl3) δ7.84(d,J=7.6Hz,1H),7.71–7.55(m,2H),7.34–7.16(m,4H),5.78(d,J=8 .0Hz,1H),5.63–5.51(m,1H),3.58–3.38(m,2H),3.29–3.12(m,1H),1.29(d,J=6.8,1.2Hz,6H). 13 C{ 1H}NMR(101MHz, CDCl3)δ167.9,163.6,146.1,141.7,139.9,136.9,128.5,127.4,125.8,125.3,121.9,121.8,83.9,77.0,39.9,36.6, 22.9,22.8.IR(neat):2967,1628,1570,1462,1414,1364,1295,1241,1217,1163,1087,1048,1001,892,824,741,708,666,619,433cm -1 HRMS (ESI) theoretical value C 18 H 19 N₂O[M+H] + :279.1492, experimental value:279.1501.[α] 29 .7 = -223.34 (c = 1.0, CHCl3).

[0433]

[0434] Ligand L15 was synthesized from 2-phenylpyridine and (1S,2R)-aminoindanol via a standard procedure. Recrystallization yielded 5.1 g of colorless crystals, with a final two-step yield of 65%. White solid, mp = 117.9–119.6 °C. 1 H NMR (400MHz, CDCl3) δ8.06–7.91(m,3H),7.84–7.72(m,2H),7.65–7.55(m,1H),7.51–7.3 5(m,3H),7.32–7.22(m,3H),5.82(d,J=8.0Hz,1H),5.66–5.52(m,1H),3.61–3.39(m,2H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ163.6,157.6,147.0,141.7,139.9,138.8,137.2,129.2,128.8,128.6,127.5,127.3,125.7,125.4,122.6,122.4,84.0 ,77.1,39.9.IR(neat):2975,1630,1564,1455,1363,1245,1164,1109, 1066,1023,1000,984,916,827,791,768,742,713,691,619,507,432cm -1 HRMS (ESI) theoretical value C 21 H 17N₂O[M+H] + :313.1335, experimental value:313.1341.[α] 24.7 = -269.91 (c = 1.0, CHCl3).

[0435]

[0436] Ligand L16 was synthesized from 2-benzylpyridine and (1S,2R)-aminoindanol via a standard procedure. It was a white solid, 3.9 g in weight, with a yield of 67% in the last two steps. 1 H NMR (400MHz, CDCl3) δ7.86 (d, J=7.6Hz, 1H), 7.70–7.50 (m, 2H), 7.41–7.15 (m, 8H), 7.06 (d ,J=8.0Hz,1H),5.80(d,J=8.0Hz,1H),5.65–5.44(m,1H),4.26(s,2H),3.61–3.41(m,2H). 13 C{ 1 H}NMR (101MHz, CDCl3) δ163.4,161.5,146.3,141.7,139.9,139.1,136.9,129.4, 128.7,128.6,127.5,126.5,125.8,125.3,125.1,121.9,84.0,77.1,44.6,39.9. IR(neat):2929,1649,1628,1567,1492,1452,1364,1296,1214,1165,1120,1103 ,1080,1025,994,941,853,797,743,717,694,671,630,594,569,521,482,450cm -1 HRMS (ESI) theoretical value C 22 H 19 N₂O[M+H] + :327.1492, Experimental value:327.1493.[α] 29.6 = -148.56 (c = 1.0, CHCl3).

[0437]

[0438] Ligand L19 was synthesized from 2-(1-ethylpropyl)pyridine and (1S,2R)-aminoindanol via a standard procedure. It is a yellow oil, 3.5 g, with a yield of 40% in the last two steps. 1H NMR (400MHz, CDCl3) δ7.85(d,J=7.6Hz,1H),7.70–7.52(m,2H),7.34–7.22(m,3H),7.17(d,J=7.8Hz,1H),5.78(d, J=8.0Hz,1H),5.62–5.51(m,1H),3.57–3.33(m,2H),2.84–2.62(m,1H),1.84–1.56(m,4H),0.77(t,J=7.2Hz,6H). 13 C{ 1 H}NMR(101MHz, CDCl3)δ165.9,163.7,146.4,141.8,140.0,136.3,128.5,127.4,125.8,125.3,123.5,121.9,83.8,77.0,51.1,3 9.9,28.0,27.9,11.9(2C).IR(neat):2959,2871,1739,1633,1571,1458,1367,1299,1162,1111,1086,990,831,819,744,624cm -1 HRMS (ESI) theoretical value C 20 H 23 N₂O[M+H] + :307.1805, Experimental value: 3071809. [α] 23.9 = -183.60 (c = 1.0, CHCl3).

[0439]

[0440] Ligand L20 was synthesized from 2-isobutylpyridine and (1S,2R)-aminoindanol via a standard procedure. It is a white solid with a yield of 54% in the last two steps. 1 H NMR (400MHz, CDCl3) δ7.85 (d, J=7.6Hz, 1H), 7.66–7.54 (m, 2H), 7.32–7.22 (m, 3H), 7.17 (d, J=8.0Hz, 1H), 5.79 (d, J=8.0Hz,1H),5.64–5.49(m,1H),3.59–3.39(m,2H),2.82–2.63(m,2H),2.20–1.98(m,1H),0.90(d,J=6.4Hz,6H). 13 C{ 1H}NMR(101MHz,CDCl3)δ163.5,161.9,146.6,141.8,140.0,136.3,128.5,127 .4,125.8,125.4,125.3,121.7,83.9,77.0,47.4,39.9,29.1,22.4,22.3.IR(n eat):3347,2957,1655,1588,1518,1448,1412,1335,1258,1176,1150,1083, 1056,994,878,843,816,767,739,706,664,632,613,582,531,507,466,423cm -1 HRMS (ESI) theoretical value C 19 H 21 N₂O[M+H] + :293.1648, experimental value:293.1641.[α] 26.6 = -214.93 (c = 1.0, CHCl3).

[0441] Example 53 Preparation of Complex 9

[0442]

[0443] A stir bar was added to a 20 mL sealed tube, followed by L5 (1 mmol, 2.0 equiv.), cobalt iodide (0.5 mmol, 1.0 equiv.), and acetonitrile (5 mL). After the addition was complete, the mixture was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction solution was filtered through a sintered glass funnel, and the filtrate was collected. Diethyl ether (20 mL) was added to the filtrate, and a large amount of green solid precipitated. The solid was filtered off through a funnel and recrystallized from methanol and ethyl acetate to obtain 250 mg of dark green crystals suitable for X-ray single-crystal diffraction, with a yield of 62%.

[0444] Crystal parameters of coordination compound 9

[0445]

[0446]

Claims

1. A compound as shown in Formula V, having the structure shown below, ； in, R 8 For C1-C 10 Alkyl, C3-C 15 cycloalkyl; The C1-C 10 The alkyl group is n-propyl, n-pentyl, or n-hexyl; The C3-C 15 The cycloalkyl groups are cyclopentyl or cyclohexyl; X is I.

2. A method for asymmetric coupling, characterized in that, It includes the following steps: in a solvent, in the presence of a Co salt, a chiral nitrogen ligand and an electrolyte, the compound shown in Formula I and the compound shown in Formula II are subjected to an electrochemical asymmetric coupling reaction as shown below to obtain the compound shown in Formula III or the compound shown in Formula IV. in: Ring A and ring A' are independently C6-C 10 aryl, with one or more R a Replacement C6-C 10 aryl, 5-10 heteroaryl, or aryl with one or more R b Substituted 5-10-membered heteroaryl groups; when multiple substituents are present, they may be identical or different; the 5-10-membered heteroaryl group may be replaced by one or more R groups. b In the heteroaryl group of the substituted 5-10 membered heteroaryl, the heteroatom is selected from N, O or S, and the number of heteroatoms is 1-3. The C6-C mentioned 10 The aryl group is phenyl or naphthyl; The 5-10 member heteroaryl group is pyridinyl or thiophene; R a and R b Independently halogenated, C1-C6 alkyl, C3-C 10 Cycloalkyl, C2-C6 alkenyl, -O-(C2-C6 alkenyl), C6-C 10 aryl, C1-C6 alkoxy, or ; R a-1 and R a-2 Alkyl groups that are independently C1-C6; R 1 and R 1 'Independently for or R 1-1 and R 1-2 Independently C1-C6 alkyl, C6-C 10 aryl or C1-C6 alkyl groups substituted with phenyl groups; R 2 and R 2 Independently H, C1-C6 alkyl, C3-C6 cycloalkenyl, C6-C 10 aryl, with one or more R 2-1 Replacement C6-C 10 aryl; R 2-1 Independently C1-C6 alkyl, C 1- C6 alkoxy group, C6-C 10 aryl, halogen, C1-C6 alkyl group substituted with one or more halogens, or ; R 2-1-1 Or R 2-1-2 Alkyl groups that are independently C1-C6; X and X' are halogens independently; The halogen mentioned is F, Cl, Br or I; The compound shown in Formula I may be the same as or different from the compound shown in Formula II; when they are different, the atomic number of X in the compound shown in Formula I is not less than the atomic number of X' in the compound shown in Formula II. The Co salt is one or more of CoI2, CoBr2·glyme, or Co(OAc)2; The chiral nitrogen ligand is selected from one or more of L5, L7, L8, L15 and L16 as shown below; ； The electrodes in the electrochemical asymmetric coupling reaction include a cathode electrode and an anode electrode. The anode electrode is one or both of iron and aluminum; the cathode electrode is one or more of platinum, gold, nickel foam, titanium, or stainless steel. The electrolyte is one or both of quaternary ammonium salts and sodium salts; The solvent is one or both of amide solvents or halocarbon solvents.

3. The method as described in claim 2, characterized in that, One or more of the following conditions must be met: (1) When R a and R b When independently a C1-C6 alkyl group, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, or n-hexyl; (2) When R a and R b Independently for C3-C 10 When cycloalkyl, the C3-C 10 The cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; (3) When R a and R b When the alkenyl group is independently C2-C6, the C2-C6 alkenyl group is vinyl, propenyl, allyl, or -CH2-(CH2)2CH=CH2; (4) When R a and R b When independently -O-(C2-C6 alkenyl), the C2-C6 alkenyl is vinyl, propenyl, allyl, or -CH2-(CH2)2CH=CH2; (5) When R a and R b Independently for C6-C 10 When the aryl group is present, the C6-C 10 The aryl group is phenyl or naphthyl; (6) When R a and R b When the alkoxy group is independently C1-C6, the C1-C6 alkoxy group is methoxy, ethoxy, isopropoxy, or tert-butoxy. (7) When R a-1 and R a-2 When independently a C1-C6 alkyl group, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, or n-hexyl; (8) When R 1-1 and R 1-2 When independently a C1-C6 alkyl group, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, or n-hexyl; (9) When R 1-1 and R 1-2 Independently for C6-C 10 When the aryl group is present, the C6-C 10 The aryl group is phenyl or naphthyl; (10) When R 1-1 and R 1-2 When independently a C1-C6 alkyl group substituted with a phenyl group; the C1-C6 alkyl group substituted with a phenyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl. (11) When R 2 and R 2 When independently a C1-C6 alkyl group, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, or n-hexyl; (12) When R 2 and R 2 When independently a C3-C6 cycloalkenyl group, the C3-C6 cycloalkenyl group is , , or ; (13) When R 2 and R 2 'Independently for C6-C 10 aryl or aryl group or one or more R 2-1 Replacement C6-C 10 The aryl group, the C6-C 10 aryl or aryl group or one or more R 2-1 Replacement C6-C 10 C6-C in aryl 10 The aryl group is phenyl or naphthyl; (14) When R 2-1 When it is independently a C1-C6 alkyl group or a C1-C6 alkyl group substituted with one or more halogens, the C1-C6 alkyl group or the C1-C6 alkyl group substituted with one or more halogens is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl. (15) When R 2-1 C 1- When the alkoxy group is C6, the C1-C6 alkoxy group is methoxy, ethoxy, isopropoxy, or tert-butoxy. (16) When R 2-1 For C6-C 10 When the aryl group is present, the C6-C 10 The aryl group is phenyl or naphthyl; (17) When R 2-1 When the C1-C6 alkyl group is substituted with one or more halogens, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, or n-hexyl. (18) When R 2-1 When the alkyl group is a C1-C6 alkyl group substituted with one or more halogens, the number of halogens is 1, 2 or 3; (19) When R 2-1-1 Or R 2-1-2 When independently a C1-C6 alkyl group, the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, or n-hexyl; (20) When X and X' are halogens independently, the halogen is Br or I.

4. The method as described in claim 3, characterized in that, One or two of the following conditions must be met: (1) When R 2-1 When the C1-C6 alkyl group is substituted with one or more halogens, the C1-C6 alkyl group is ethyl, n-propyl, isopropyl, or tert-butyl. (2) When R 2-1-1 Or R 2-1-2 When independently a C1-C6 alkyl group, the C1-C6 alkyl group is methyl.

5. The method as described in claim 4, characterized in that, When R 2-1 When R is a C1-C6 alkyl group substituted with one or more halogens, 2-1 It is trifluoromethyl.

6. The method as described in claim 2, characterized in that, One or more of the following conditions must be met: (1) Ring A and ring A' are independent , , , , , , , , , , , , , , , or ; (2) R 1 and R 1 Independently -OBn or -CO2Ph; (3) R 2 and R 2 'Independently H, methyl, phenyl, naphthyl, , , , , , , , , , , , , , or ; (4) In the compound shown in Formula I, R 2 Located at the para or meta position of X; in the chemical shown in Formula II, R 2 'Located opposite or between X'.

7. The method as described in claim 2, characterized in that, One or two of the following conditions must be met: (1) When the compound represented by Formula I is not the same as the compound represented by Formula II, the compound represented by Formula I, the compound represented by Formula II, and the corresponding compound represented by Formula III are any of the following groups: 、 、 、 、 、 、 、 、 、 、 、 、 、 or ； (2) When the compound represented by Formula I is the same as the compound represented by Formula II, the compound represented by Formula I is selected from the following structures: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

8. The method according to any one of claims 2-7, characterized in that, One or more of the following conditions must be met: (1) When the compound shown in Formula I is different from the compound shown in Formula II, the chiral nitrogen ligand is L16; when the compound shown in Formula I is the same as the compound shown in Formula II, the chiral nitrogen ligand is L12. (2) The quaternary ammonium salt is Et4NBF4, n -Bu4NBF4、Et4NPF6 n -Bu4NPF6、Et4NClO4 n -Bu4NClO4, Et4NOAc n -Bu4NOAc, Et4NOTs n -Bu4NOTs、 n -One or more of Bu4NI and H4NCl; (3) The sodium salt is one or more of NaCl, NaBr, NaI and NaOAc; (4) The solvent is one or more of DMF, DMAc, dichloromethane and trichloromethane; (5) The electrochemical asymmetric coupling reaction is further enhanced with a desiccant, which is one or more of Na2SO4, MgSO4 and molecular sieve; (6) The molar concentration of the compound of formula I in the solvent is 0.01-1 mol / L; (7) The molar concentration of the compound of formula II in the solvent is 0.01-1 mol / L; (8) The molar concentration of the electrolyte in the solvent is 0.01-1 mol / L; (9) The molar ratio of the electrolyte to the compound shown in Formula I is 1:1 to 1:10; (10) The molar ratio of the Co salt to the chiral nitrogen ligand is 1:1 to 1:5; (11) The current value of the electrochemical asymmetric coupling reaction is 0.1-20 mA; (12) The electrochemical asymmetric coupling reaction is carried out at 0-150℃; (13) When the compound shown in Formula I is different from the compound shown in Formula II, X in the compound shown in Formula I is I, and R is R. 1 For -OBn; in the compounds shown in Formula II, X' is Br, R 1’ It is -CO2Ph.

9. The method as described in claim 8, characterized in that, One or more of the following conditions must be met: (1) The anode electrode is made of iron; (2) The cathode electrode is made of stainless steel and nickel foam; (3) The quaternary ammonium salt is n -Bu4NBF4、 n -Bu4NPF6, Et4NOTs and n One or more of -Bu4NI; (4) The sodium salt is NaI; (5) The solvent is one or both of DMF and DMAc; (6) The Co salt is CoI2; (7) The electrochemical asymmetric coupling reaction is further enhanced with a desiccant, which is a molecular sieve; (8) The molar concentration of the compound of formula I in the solvent is 0.02-0.5 mol / L; (9) The molar concentration of the compound of formula II in the solvent is 0.02-0.8 mol / L; (10) The molar concentration of the electrolyte in the solvent is 0.02-0.6 mol / L; (11) The molar ratio of the electrolyte to the compound shown in Formula I is 1:1-2:5; (12) The molar ratio of the Co salt to the chiral nitrogen ligand is 1:2; (13) The current value of the electrochemical asymmetric coupling reaction is 1-6 mA; (14) The electrochemical asymmetric coupling reaction is carried out at 0-80℃; (15) The electrochemical asymmetric coupling reaction described herein is carried out at 10-30℃; (16) When the compound shown in Formula I is not the same as the compound shown in Formula II, the molar ratio of the compound shown in Formula I to the compound shown in Formula II is 1:1-5:

1. (17) When the compound shown in Formula I is the same as the compound shown in Formula II, the total amount of the compound shown in Formula I and the compound shown in Formula II is in a molar ratio of 1:1 to 10:1 to the chiral nitrogen ligand. (18) When the compound shown in Formula I is not the same as the compound shown in Formula II, the molar ratio of the compound shown in Formula I to the chiral nitrogen ligand is 1:1 to 10:

1.

10. The method according to any one of claims 2-7, characterized in that, One or more of the following conditions must be met: (1) The molar concentration of the compound of formula I in the solvent is 0.06-0.25 mol / L; (2) The molar concentration of the compound of formula II in the solvent is 0.06-0.5 mol / L; (3) The molar concentration of the electrolyte in the solvent is 0.06-0.25 mol / L; (4) The solvent is DMF or DMAc; (5) When the compound shown in Formula I is the same as the compound shown in Formula II, the anode electrode is iron and the cathode electrode is stainless steel; (6) When the compound shown in Formula I is not the same as the compound shown in Formula II, the anode electrode is iron and the cathode electrode is nickel foam. (7) When the compound shown in Formula I is not the same as the compound shown in Formula II, the molar ratio of the compound shown in Formula I to the compound shown in Formula II is 1:1-2:

1. (8) When the compound shown in Formula I is the same as the compound shown in Formula II, the total amount of the compound shown in Formula I and the compound shown in Formula II is in a molar ratio of 5:1 to 7:1 to the chiral nitrogen ligand. (9) When the compound shown in Formula I is not the same as the compound shown in Formula II, the molar ratio of the compound shown in Formula I to the chiral nitrogen ligand is 5:1-7:

1.

11. A compound having the structure shown below, 。 12. The application of the compound as described in claim 11 in asymmetric synthesis, characterized in that, The application is as a catalyst ligand in the electrochemical asymmetric coupling reaction as described in any one of claims 2-10.

13. The use of a compound of formula V as described in claim 1 in asymmetric synthesis, characterized in that, The application is as a catalyst in the electrochemical asymmetric coupling reaction as described in any one of claims 2-10.

Images