CN116988078A - Metal catalyzed asymmetric coupling method promoted by electrochemical reduction - Google Patents

Abstract

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

Description

A metal-catalyzed asymmetric coupling method promoted by electrochemical reduction

Technical Field

The invention belongs to the technical field of organic synthesis, and in particular relates to an asymmetric coupling method of metal catalysis promoted by electrochemical reduction.

Background Art

The construction of axially chiral biaryls is important because they are fundamental building blocks found in ligands, organocatalysts, and natural products. In the past decade, various methods have been developed to synthesize atropisomeric biaryls, including transition metal-catalyzed enantioselective syntheses via cross-coupling between aryl halides and aryl metal species, the latter consisting of organomagnesium, organozinc, organoboron, or organoindium reagents. Since aryl metal reagents are usually prepared from the corresponding aryl halides, the enantioselective reductive coupling of two aryl halides to obtain axially chiral biaryls would provide an attractive step-economic 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 biaryls is rare. Therefore, the development of a highly enantioselective Ni-catalyzed reductive coupling of aryl halides to form biaryls with a broad substrate scope would provide a complementary and alternative approach to the traditional cross-coupling and oxidative coupling methods for biaryl synthesis. The past decade has witnessed a renaissance in electrochemical organic synthesis driven by the need for more atom-economic reaction platforms to address growing global sustainability issues and awareness. As part of our ongoing interest in combining cathodic reduction with transition metal catalysis, we developed the first example of nickel-catalyzed electrochemical enantioselective construction of axially chiral biaryls.

Summary of the invention

The purpose of the present invention is to overcome the defects of the existing preparation technology and provide an electrochemical reduction-promoted metal-catalyzed asymmetric coupling method which has the characteristics of high selectivity, mild reaction conditions, environmental friendliness, high yield and good purity and is suitable for industrial production.

A preparation method for asymmetric coupling, comprising the following steps: in a solvent, in the presence of a Co salt, a chiral nitrogen ligand and an electrolyte, subjecting a compound as shown in formula I and a compound as shown in formula II 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;

in:

Ring A and Ring A' are independently _C6 - _C10 aryl, _C6 - _{C10 aryl} ^substituted by one or more Ra, 5-10 membered heteroaryl or 5-10 membered heteroaryl substituted by one or more ^Rb ; when there are multiple substituents, they are the same or different; in the 5-10 membered heteroaryl or the 5-10 membered heteroaryl substituted by one or more ^Rb , the heteroatom is selected from N, O or S, and the number of heteroatoms is 1-3;

^Ra and ^Rb are independently halogen, _C1 - _C30 alkyl, _C3 - _C30 cycloalkyl, _C2 - _C30 alkenyl, -O-( _C2 - _C30 alkenyl), _C6 - _C30 aryl, _C1 - _C30 alkoxy,

Ra ^-1 and Ra ^-2 are independently _C1 - _C30 alkyl groups;

R ¹ and R ¹ 'are independently R ^1-1 and R ^1-2 are independently C ₁ -C ₃₀ alkyl, C ₆ -C ₃₀ aryl, or C ₁ -C ₃₀ alkyl substituted with phenyl;

R ² and R ² 'are independently H, C ₁ -C ₃₀ alkyl, C ₄ -C ₃₀ cycloalkenyl, C ₆ -C ₃₀ aryl, or C ₆ -C ₃₀ aryl substituted by one or more R ^2-1 ;

R ^2-1 is independently C ₁ -C ₃₀ alkyl, C _{1 -C 30} alkoxy, C ₆ -C ₃₀ aryl, halogen, C ₁ -C ₃₀ alkyl substituted by one or more halogens,

R ^2-1-1 or R ^2-1-2 is independently a C ₁ -C ₃₀ alkyl group;

X and X' are independently halogen;

The compound of formula I is the same as or different from the compound of formula II; when they are different, the atomic number of X in the compound of formula I is not less than the atomic number of X' in the compound of formula II.

In certain preferred embodiments of the present invention, certain groups in the compounds shown in Formulae I, II, III and IV are defined as follows, and the unmentioned groups are the same as those described in any embodiment of the present invention (referred to as "in some embodiments").

In some embodiments, when Ring A and Ring A' are independently C ₆ -C ₁₀ aryl and C ₆ -C ₁₀ aryl substituted by one or more ^Ra , the C ₆ -C ₁₀ aryl and the C _{6 -C 10} aryl substituted by one or more ^Ra are independently phenyl or _naphthyl , for example phenyl.

In some embodiments, when Ring A and Ring A' are independently 5-10 membered heteroaryl or 5-10 membered heteroaryl substituted by one or more R ^b , the 5-10 membered heteroaryl is pyridyl or thienyl, such as pyridyl.

In some embodiments, when ^Ra and ^Rb are independently halogen, the halogen is F, Cl, Br or I.

In some embodiments, when ^Ra and ^Rb are independently C1- _C30 alkyl, the C1 _{- C30} alkyl may be _C1 - _C10 alkyl; for example, _C1 - _C6 alkyl, for example, methyl, ethyl, n- _propyl , isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; for example, methyl, ethyl or n-pentyl.

In some embodiments, when ^Ra and ^Rb are independently C3- _C30 cycloalkyl groups, _the C3- _C30 cycloalkyl groups _may be C3- _C10 cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, _and cyclohexyl; and another example is cyclopropyl and cyclohexyl.

In some embodiments, when ^Ra and ^Rb are independently C2- _C30 alkenyl, _the C2 _{-C30 alkenyl} may be _C2 - _C10 alkenyl; for example, _C2 - _C6 alkenyl, for example, vinyl, propenyl, allyl or _-CH2- ( _CH2 ) _2CH = _CH2 ; for example, vinyl.

In some embodiments, when ^Ra and ^Rb are independently -O-( _C2 - _C30 alkenyl), the _C2 - _C30 alkenyl may be _C2 - _C10 alkenyl; for example, C2- _C6 alkenyl, for example, ethenyl, propenyl, allyl or _-CH2- ( _CH2 ) _2CH = _CH2 ; for example _{, -CH2-} ( _CH2 ) _2CH = _CH2 .

In some embodiments, when ^Ra and ^Rb are independently C6 _{- C30 aryl} groups, the C6 _{- C30} aryl groups may be C6- _C10 aryl groups, such as phenyl or naphthyl.

In some embodiments, when ^Ra and ^Rb are independently C1 _{- C30} alkoxy groups, the C1 _{-C30 alkoxy} groups may be C1- _C10 alkoxy groups, such as _C1 - _C6 alkoxy groups, methoxy groups, ethoxy groups, isopropoxy groups, tert _- butoxy groups, and methoxy groups.

In some embodiments, when Ra ^-1 and Ra ^-2 are independently _C1 - _C30 alkyl groups, the _C1 - _C30 alkyl group may be a _C1 - _C10 alkyl group; for example, a _C1 - _C6 alkyl group, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl, and for example, methyl.

In some embodiments, when R ^1-1 and R ^1-2 are independently C ₁ -C ₃₀ alkyl groups, the C ₁ -C ₃₀ alkyl group may be a C ₁ -C ₁₀ alkyl group; for example, a C ₁ -C ₆ alkyl group, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; for example, methyl.

In some embodiments, when R ^1-1 and R ^1-2 are independently C ₆ -C ₃₀ aryl groups, the C ₆ -C ₃₀ aryl groups may be C ₆ -C ₁₀ aryl groups, such as phenyl or naphthyl.

In some embodiments, when R ^1-1 and R ^1-2 are independently C ₁ -C ₃₀ alkyl substituted by phenyl; the C ₁ -C ₃₀ alkyl in the C ₁ -C ₃₀ alkyl substituted by phenyl may be C ₁ -C ₁₀ alkyl; for example, C ₁ -C ₆ alkyl, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; for example, methyl.

In some embodiments, when R ² and R ² 'are independently C ₁ -C ₃₀ alkyl groups, the C ₁ -C ₃₀ alkyl group may be C ₁ -C ₁₀ alkyl group; for example, C ₁ -C ₆ alkyl group, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; for example, methyl.

In some embodiments, when R ² and R ² 'are independently C ₃ -C ₃₀ cycloalkenyl, the C ₁ -C ₃₀ cycloalkenyl may be C ₃ -C ₁₀ cycloalkenyl; for example, C ₃ -C ₆ cycloalkenyl, for example For example,

In some embodiments, when R ² and R ² ' are independently C ₆ -C ₃₀ aryl or C ₆ -C ₃₀ aryl substituted by one or more R 2-1, the C ₆ -C ₃₀ aryl or the C ₆ -C ₃₀ aryl substituted by one _or more R ^2-1 may be a _{C 6} -C ₁₀ aryl, such as phenyl or ^naphthyl .

In some embodiments, when R ^2-1 is independently a C ₁ -C ₃₀ alkyl group or a C ₁ -C ₃₀ alkyl group substituted by one or more halogens, the C ₁ -C ₃₀ alkyl group or the C ₁ -C ₃₀ alkyl group substituted by one or more halogens may be a C ₁ -C ₁₀ alkyl group; for example _, a C ₁ -C ₆ alkyl group, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n _- hexyl; for example, ethyl, n-propyl, isopropyl or tert-butyl.

In some embodiments, when R ^2-1 is a C _1- C ₃₀ alkoxy group, the C ₁ -C ₃₀ alkoxy group may be a C ₁ -C ₁₀ alkoxy group; for example, a C ₁ -C ₆ alkoxy group, for example, a methoxy group, an ethoxy group, an isopropoxy group, a tert-butoxy group; for example, a methoxy group.

In some embodiments, when R ^2-1 is a C ₆ -C ₃₀ aryl group, the C ₆ -C ₃₀ aryl group may be a C ₆ -C ₁₀ aryl group, such as a phenyl group or a naphthyl group.

In some embodiments, when R ^2-1 is halogen or C ₁ -C ₃₀ alkyl substituted by one or more halogens, the halogen or the halogen in the C ₁ -C ₃₀ alkyl substituted by one or more halogens is F, Cl, Br or I.

In some embodiments, when R ^2-1 is a C ₁ -C ₃₀ alkyl group substituted by one or more halogens, the C ₁ -C ₃₀ alkyl group may be a C ₁ -C ₆ alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; and also such as ethyl, n-propyl, isopropyl or tert-butyl.

In some embodiments, when R ^2-1 is a C ₁ -C ₃₀ alkyl group substituted by one or more halogens, the number of the halogens may be 1, 2 or 3; for example, trifluoromethyl.

In some embodiments, when R ^2-1-1 or R ^2-1-2 is independently a C ₁ -C ₃₀ alkyl group, the C ₁ -C ₃₀ alkyl group may be a C ₁ -C ₁₀ alkyl group; for example, a C ₁ -C ₆ alkyl group, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; for example, methyl.

In some embodiments, when X and X' are independently halogen, the halogen is F, Cl, Br or I, such as Br or I.

In some embodiments, the C ₆ -C ₃₀ aryl group substituted by one or more R ^2-1 is selected from

In some embodiments, when the compound of formula I is different from the compound of formula II, X in the compound of formula I is I, and R ¹ is -OBn; X' in the compound of formula II is Br, and R ^1' is -CO ₂ Ph.

In some embodiments, ^Ra and ^Rb are independently H, F, methyl, ethyl, n-pentyl, cyclopropyl, cyclohexyl, methoxy, vinyl, phenyl, -COOCH3, _-OCH2 ( _CH2 ) _2CH = _{CH2 ,}

In some embodiments, Ring A and Ring A' are independently

In some embodiments, R ¹ and R ¹ ′ are independently —OBn or —CO ₂ Ph.

In some embodiments, R ² and R ² 'are independently H, methyl, phenyl, naphthyl,

In some embodiments, in the compound of Formula I, R ² is located at the para or meta position relative to X; in the compound of Formula II, R ² ' is located at the para or meta position relative to X'.

In some embodiments, the compound as shown in Formula I and the compound as shown in Formula II are independently

In some embodiments, the compound shown in Formula III is

or an enantiomer thereof.

In some embodiments, when the compound of formula I is different from the compound of formula II, the compound of formula I, the compound of formula II and the corresponding compound of formula III are any of the following groups: or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof.

In some embodiments, the chiral nitrogen ligand is a compound as shown in Formula IV or an enantiomer thereof,

wherein R ⁴ and R ⁵ are independently H, C ₁ -C ₁₀ alkyl, C ₃ -C ₁₅ cycloalkyl, C ₆ -C ₁₀ aryl, or C ₁ -C ₁₀ alkyl substituted with phenyl;

Alternatively, ^R4 and ^R5 together with the attached carbon form: Where n is 0-6, such as 1 or 2;

R ⁶ and R ⁷ are independently H, phenyl or naphthyl, and R ⁶ and R ⁷ are not H at the same time;

Alternatively, ^R6 and ^R7 together with the attached carbon form:

In some embodiments, when R ⁴ and R ⁵ are C ₁ -C ₁₀ alkyl, the C ₁ -C ₁₀ alkyl may be C ₁ -C ₆ alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl or -CH(CH ₂ CH ₃ ) ₂ ; another example is methyl, ethyl, n-propyl, isopropyl, n-butyl or -CH(CH ₂ CH ₃ ) ₂ .

In some embodiments, when R ⁴ or R ⁵ is a C ₃ -C ₁₅ cycloalkyl group, the C ₃ -C ₁₅ cycloalkyl group may be a C ₃ -C ₁₂ cycloalkyl group, such as cyclopropyl, cyclopentyl, cyclohexyl, and cyclooctyl.

In some embodiments, when R ⁴ or R ⁵ is a C ₆ -C ₁₀ aryl group, the C ₆ -C ₁₀ aryl group is a phenyl group or a naphthyl group.

In some embodiments, when ^R4 or ^R5 is a _C1 - _C10 alkyl substituted by a phenyl group; the _C1 - _C10 alkyl group may be a _C1 - _C6 alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert- _butyl , n-pentyl, n-hexyl or -CH( _CH2CH3 ) ₂ ; another example is methyl, ethyl, n-propyl, isopropyl, n-butyl or _-CH ( _CH2CH3 ) ₂ .

In some embodiments, R ⁴ and R ⁵ are independently H, methyl, ethyl, n-propyl, isopropyl, n-butyl, -CH(CH ₂ CH ₃ ) ₂ , cyclopropyl, cyclopentyl, cyclohexyl, cyclooctyl, phenyl or benzyl; for example, R ⁵ is independently H, and R ⁴ is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, -CH(CH ₂ CH ₃ ) ₂ , cyclopropyl, cyclopentyl, cyclohexyl, cyclooctyl, phenyl or benzyl.

In some embodiments, R ⁶ and R ⁷ are independently H or phenyl; for example, R ⁶ is independently H, and R ⁷ is independently phenyl.

In some embodiments, the chiral nitrogen ligand can be 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 as shown below, or an enantiomer thereof; preferably L16 or L12, or an enantiomer thereof.

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

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, 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; most preferably stainless steel and nickel.

In some embodiments, when the compound represented by Formula I is the same as the compound represented by Formula II, the anode electrode is iron, and the cathode electrode is stainless steel.

In some embodiments, when the compound of Formula I is different from the compound of Formula II, the anode electrode is iron and the cathode electrode is nickel.

In some embodiments, the electrolyte is a conventional electrolyte in this type of reaction in the art, preferably _one or _more of _a quaternary ammonium salt (for example, one or _more of _Et4NBF4 , n _{- Bu4NBF4} , _Et4NPF6 , n _{- Bu4NPF6} , _{Et4NClO4 ,} n-Bu4NClO4, Et4NOAc, n- _Bu4NOAc , _Et4NOTS , n- _Bu4NOTS , _n - _Bu4NI and _H4NCl ), a sodium salt (for example, one or more of NaCl, NaBr, NaI and NaOAc) and a lithium salt (for example, _LiBr and/or LiCl); more preferably one or _more of n- _Bu4NBF4 , n- _Bu4NPF6 , _Et4NOTS , n- _Bu4NI , LiBr and NaI, and most preferably NaI.

In some embodiments, the solvent is a conventional solvent in this type of reaction in the art, preferably one or more of an amide solvent (e.g., DMF and/or DMAc), a halogenated hydrocarbon solvent (e.g., dichloromethane and/or chloroform), a nitrile solvent (e.g., acetonitrile) and an alcohol solvent (e.g., one or more of methanol, ethanol and isopropanol); more preferably one or more of DMF, DMAc and acetonitrile; most preferably DMF or DMAc.

In some embodiments, the Co salt is one or more of a Co(I) compound (e.g., CoCl(PPh ₃ ) ₂ ), a Co(II) compound (e.g., one or more of CoI ₂ , CoCl ₂ , CoBr ₂ ·glyme, Co(OAc) ₂ , Co(C ₂ O ₄ ) ₂ ), and a Co(III) compound (e.g., Co(acac) ₃ ); preferably one or more of CoI ₂ , CoCl ₂ , CoBr ₂ ·glyme, Co(OAc) ₂ , CoCl(PPh ₃ ) ₂ , Co ₂ (acac) ₃ , Co(C ₂ O ₄ ) ₂ ; most preferably CoI ₂ .

In some embodiments, a desiccant is further added. The desiccant may be a conventional desiccant in the art, such as one or more of Na ₂ SO ₄ , MgSO ₄ and molecular sieves, and molecular sieves are most preferred.

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 (eg 0.06-0.25 mol/L).

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 (eg 0.06-0.5 mol/L).

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 (eg, 0.06-0.25 mol/L).

In some embodiments, the molar ratio of the electrolyte to the compound represented by Formula I may be a conventional molar ratio in the art, preferably 1:1-1:10 (eg, 1:1-2:5).

In some embodiments, when the compound of Formula I is different from the compound of Formula II, the molar ratio of the compound of Formula I to the compound of Formula II is 1:1-5:1 (eg, 1:1-2:1).

In some embodiments, when the compound as shown in Formula I is the same as the compound as shown in Formula II, the molar ratio of the total amount of the compound as shown in Formula I and the compound as 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).

In some embodiments, when the compound as shown in Formula I is different from the compound as shown in Formula II, the molar ratio of the compound as shown in Formula I 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).

In some embodiments, the molar ratio of the Co salt to the chiral nitrogen ligand may be a conventional ratio in the art, preferably 1:1-1:5 (eg, 1:2).

In some embodiments, the current value of the electrochemical asymmetric coupling reaction is 0.1-20 mA (eg, 1-6 mA).

In a certain embodiment of the present invention, the electrochemical asymmetric coupling reaction is preferably carried out at 0-150°C, more preferably at 0-80°C (eg 10-30°C).

In some embodiments, when the chiral nitrogen ligand is a compound as shown in Formula IV, the compound as shown in Formula III is in R configuration; when the chiral nitrogen ligand is an enantiomer of the compound as shown in Formula IV (for example, L12), the compound as shown in Formula III is in S configuration.

In a certain embodiment 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 R configuration.

The present invention also relates to a catalyst composition, which consists of the chiral nitrogen ligand and the Co salt.

In one embodiment of the present invention, the chiral nitrogen ligand in the catalyst composition as 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 an enantiomer thereof; preferably L8 or L12;

In one embodiment of the present invention, the Co salt in the catalyst composition is selected from one or more of CoI ₂ , CoCl ₂ , CoBr ₂ ·glyme, Co(OAc) ₂ , CoCl(PPh ₃ ) ₂ , Co ₂ (acac) ₃ and Co(C ₂ O ₄ ) ₂ .

In a certain 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 1:1-1:5 (eg 1:2).

In a certain embodiment of the present invention, in the catalyst composition, the chiral nitrogen ligand is partially or completely complexed with the compound shown in formula IV, that is, exists in the form of a complex.

In a certain embodiment of the present invention, the catalyst composition may be a catalyst composition for electrochemical asymmetric catalysis.

The present invention also relates to a compound as shown in formula V or an enantiomer thereof,

in,

^R8 is H, _C1 - _C10 alkyl, _C3 - _C15 cycloalkyl, _C6 - _C10 aryl, or _C1 - _C10 alkyl substituted by phenyl;

X is halogen.

In some embodiments, in the compound of formula V or its enantiomer as described above, when X is halogen, Br or I is preferred, and I is most preferred.

In some embodiments, in the compound of formula V or its enantiomer as described above, when ^R8 is _C1 - _C10 alkyl or _C1 - _C10 alkyl substituted with phenyl, the C1- _C10 alkyl in the _C1 - _C10 alkyl or _C1 - _C10 alkyl substituted with phenyl may 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.

In some embodiments, when R ⁸ is a C ₃ -C ₁₅ cycloalkyl group, the C ₃ -C ₁₅ cycloalkyl group may be a C ₃ -C ₁₂ cycloalkyl group, such as cyclopropyl, cyclopentyl, cyclohexyl, and cyclooctyl.

In some embodiments, when R ⁸ is C ₆ -C ₁₀ aryl, the C ₆ -C ₁₀ aryl is phenyl or naphthyl.

In some embodiments, when R ⁸ is a C ₁ -C ₁₀ alkyl substituted by a phenyl group, the C ₁ -C ₁₀ alkyl substituted by a phenyl group is a benzyl group.

In some embodiments, the compound of formula V or its enantiomer may be a compound of formula VI or its enantiomer,

Among them, X is F, Cl, Br, I, preferably I.

In some embodiments, the cobalt complex described above can be prepared by the following method: the chiral nitrogen ligand described above and the cobalt compound described above are reacted in a solvent by self-assembly.

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

In some embodiments, the conditions and operation methods of the asymmetric synthesis may be as shown in the conditions and operation methods of the asymmetric coupling method described above.

Unless otherwise specified, the terms used in the present invention have the following meanings:

In this specification, groups and substituents thereof can be selected by those skilled in the art to provide stable structural moieties and compounds. When substituents are described by conventional chemical formulas written from left to right, the substituents also include chemically equivalent substituents obtained when the structural formula is written from right to left.

Certain chemical groups defined herein are preceded by a shorthand notation to indicate the total number of carbon atoms present in the group. For example, _C1 - _C6 alkyl refers to an alkyl group as defined below having a total of 1, 2, 3, 4, 5 or 6 carbon atoms. The total number of carbon atoms in the shorthand notation does not include carbons that may be present in substituents of the group.

As used herein, numerical ranges defined in substituents such as 0 to 4, 1-4, 1 to 3, etc. indicate integers within the range, such as 1-6 is 1, 2, 3, 4, 5, 6.

In addition to the foregoing, when used in the specification and claims of the present application, the following terms have the meanings indicated below unless otherwise specifically stated.

The term "one or more" or "one or more than two" means 1, 2, 3, 4, 5, 6, 7, 8, 9 or more.

The term "comprising" is an open expression, that is, including the contents specified in the present invention but not excluding other contents.

The term "substituted" means that any one or more hydrogen atoms on a particular atom are replaced by a substituent, including deuterium and hydrogen variants, as long as the valence state of the particular atom is normal and the substituted compound is stable.

In general, the term "substituted" means that one or more hydrogen atoms in a given structure are replaced 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 substituents may be different or the same. Unless otherwise indicated, a substituent group may be substituted at each substitutable position of the substituted group. When more than one position in the given structural formula can be substituted by one or more substituents selected from a specific group, the substituents may be substituted at each position in the same or different manner.

In various parts of this specification, the substituents of the compounds disclosed in the present invention are disclosed according to the group type or range. It is particularly pointed out that the present invention includes each independent secondary combination of the members of these group types and ranges. The term " _Cx - _Cy alkyl" refers to a straight or branched saturated hydrocarbon containing x to y carbon atoms. For example, the term " _C1 - _C6 alkyl" or " _C1-6 alkyl" specifically refers to the independently disclosed methyl, ethyl, _C3 alkyl, _C4 alkyl, _C5 alkyl and _C6 alkyl; " _C1-4 alkyl" specifically refers to the independently disclosed methyl, ethyl, _C3 alkyl (i.e., propyl, including n-propyl and isopropyl), _C4 alkyl (i.e., butyl, including n-butyl, isobutyl, sec-butyl and tert-butyl).

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

The term "alkoxy" refers to a group ^-ORX , wherein ^RX is alkyl as defined above.

When a substituent is listed without indicating the atom through which it is attached to a compound included in the chemical formula but not specifically mentioned, such substituent may be bonded via any atom thereof. Combinations of substituents and/or variations thereof are permissible only if such combinations result in stable compounds.

When there is no explicit indication of substitution in the listed groups, such groups are only unsubstituted. For example, when "C ₁ -C ₄ alkyl" is not preceded by "substituted or unsubstituted", it only refers to "C ₁ -C ₄ alkyl" itself or "unsubstituted C ₁ -C ₄ alkyl".

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

In some specific structures, when an alkyl group is clearly indicated as a linking group, the alkyl group represents a linked alkylene group, for example, the C ₁ -C ₆ alkyl in the group "halo-C ₁ ～C ₆ alkyl" should be understood as C ₁ ～C ₆ alkylene.

The term "alkylene" refers to a saturated divalent hydrocarbon group derived from a saturated straight or branched hydrocarbon group by removing two hydrogen atoms. Examples of alkylene groups include methylene ( _-CH2- ), ethylene {including _-CH2CH2- or -CH( _CH3 )-}, isopropylene {including -CH( _CH3 ) _CH2- or -C( _{CH3 ) 2-} } and the like.

In this application, as a group or part of other groups (for example, in groups such as halogen-substituted alkyl), the term "alkyl" means a saturated aliphatic hydrocarbon group including branched and straight chains with a specified number of carbon atoms; for example, a straight or branched saturated hydrocarbon chain containing 1 to 30 carbon atoms; for example, a _C1 - _C6 alkyl group. As defined in " _C1 - _C6 alkyl", it includes groups having 1, 2, 3, 4, 5, or 6 carbon atoms in a straight or branched structure. Among them, 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); 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).

The term "haloalkyl" refers to an alkyl group substituted with one or more halogens, such as trifluoromethyl, wherein "plurality", "halogen" and "alkyl" are as defined above.

The term "cycloalkyl" refers to a saturated monocyclic or polycyclic carbocyclic substituent consisting only of carbon atoms and hydrogen atoms, and it can be connected to the rest of the molecule by a single bond via any suitable carbon atom; when it is polycyclic, it can be a cyclic system, a bridged ring system or a spirocyclic system that is connected in parallel, connected in bridged rings or connected in spiro (i.e., two geminal hydrogen atoms on the carbon atom are replaced by alkylene). In a certain embodiment, a monovalent saturated cyclic alkyl having 3-30 ring carbon atoms, more preferably 3-7 carbon atoms, is preferred. In a certain embodiment, a typical monocyclic cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

In the present application, the term "cycloalkenyl" refers to an unsaturated non-aromatic group containing a double bond, either by itself or as part of another substituent. It contains a monocyclic, polycyclic or bridged carbocyclic substituent with a partially unsaturated double bond, and it can be connected to the rest of the molecule through a single bond via any suitable carbon atom; when it is polycyclic, it can be a bridged ring system or a spirocyclic system that is connected in parallel or spirocyclic (i.e., two geminal hydrogens on the carbon atom are replaced by alkylene). In some embodiments, "C2-C30 cycloalkenyl" preferably has a non-aromatic group containing a double bond of 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.

The term "heterocycloalkyl" refers to a saturated monocyclic group having heteroatoms, preferably a 3-7 membered saturated monocyclic ring containing 1, 2 or 3 ring heteroatoms independently selected from N, O and S. Examples of heterocycloalkyl are: pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydropyridinyl, tetrahydropyrrolyl, azetidinyl, thiazolidinyl, oxazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, azepanyl, diazepanyl, oxazepanyl, dioxolanyl, dioxanyl, etc. Preferred heterocyclyls are 1,3-dioxolanyl and 1,4-dioxanyl.

The term "aryl" refers to an all-carbon aromatic group with a specified number of carbon atoms and a completely conjugated π electron system (for example, when it is a bicyclic or tricyclic ring, each ring satisfies the Huckel rule), which can be a single ring or a condensed ring, usually having 6-20 carbon atoms, preferably 6-14 carbon atoms, and most preferably 6 carbon atoms. Examples of aryl include, but are not limited to, monocyclic aryl such as C ₆ aryl (phenyl), bicyclic aryl such as C ₁₀ aryl (naphthyl), tricyclic aryl such as C ₁₄ aryl (phenanthrenyl and anthracenyl).

The term "heteroaryl" refers to an aromatic group containing heteroatoms, which may be a monocyclic or condensed ring, preferably a 5-10 membered heteroaryl group containing 1-4 independently selected from N, O and S, including but not limited to pyrrolyl, furanyl, thienyl, indolyl, imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, (benzo)oxazolyl, (benzo)furanyl, (benzo)thienyl, (benzo)thiazolyl, triazolyl. In a certain embodiment, it is typically a 5-6 membered monocyclic heteroaryl group containing one or more heteroatoms independently selected from N, O and S. In a certain 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.

Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

The reagents and raw materials used in the present invention are commercially available.

Compared with the prior art, the present invention provides a technical solution to combine a chiral group ligand with a transition metal catalyst to obtain an optically active axial chiral biaryl compound under electrochemical reduction conditions. The synthesis method has the characteristics of high selectivity, mild reaction conditions, environmental friendliness, high yield and good purity. Therefore, the present invention has good practical value.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1: Thermal ellipsoid diagram of Co complex crystal

DETAILED DESCRIPTION

The present invention is further described below through specific embodiments, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments, and all technologies implemented based on the above content of the present invention belong to the scope of the present invention.

All reagents in this article were purchased directly without further purification. Column chromatography silica gel used 100-200 mesh or 300-400 mesh. Thin plate chromatography was visualized by ultraviolet or iodine. All reagents were purchased from TCI, sigma-Aldrich, Adamas-beta, J&K, Bid Pharmaceuticals, Jiuding Pharmaceuticals, and Anaiji Chemicals, all of which were commercially available with the highest 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. H NMR and ¹³ C{ ¹ H} NMR were obtained on Agilent AV 400, Varian Inova 400, Bruker 400 (400 MHz and 100 MHz, respectively). ¹⁹ F NMR was obtained on Agilent AV400, Varian Inova 400 (376 MHz). NMR standards were calibrated with TMS or deuterated solvents.

General steps

Method A: Self-coupling (0.3 mmol)

Reaction procedure (0.3 mmol scale): In a glove box, add a stirrer to the reaction tube of an IKA 2.0 electrochemical synthesizer, 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), N,N-dimethylformamide (5 mL), an iron electrode as an anode and a stainless steel electrode as a cathode were installed in an IKA reactor. The reaction device was placed at room temperature and stirred for 30 minutes. After stirring, 1 mA was turned on to react for 24 hours. After the reaction, the reaction solution was passed through diatomaceous earth and rinsed with dichloromethane. The solvent was removed by rotary evaporation and purified by rapid column chromatography to obtain the corresponding product.

Method B: Cross coupling (0.3 mmol)

Reaction operation steps: In a glove box, add a stirrer to the reaction tube of an IKA 2.0 electrochemical synthesizer, 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%), sodium iodide (0.3 mmol, 1.0 equiv.), Molecular sieves (70 mg), N,N-dimethylacetamide (5 mL), iron electrode as anode and stainless steel electrode as cathode were installed in IKA 2.0 reactor. The reaction device was placed at room temperature and stirred for 30 minutes. After stirring, 1 mA was energized and reacted for 24 hours. After the reaction, ethyl acetate (80 mL) was added to the reaction solution to dilute the reaction solution, and the reaction solution was neutralized with dilute hydrochloric acid. The organic phase was washed with saturated ammonium chloride (20 mL × 3), and the organic phase was dried with anhydrous magnesium sulfate, filtered, the solvent was removed by rotary evaporation, and the corresponding product was purified by flash column chromatography.

Method C: Self-coupling (5 mmol)

Reaction procedure (5 mmol scale): In a glove box, add a stirrer to an electrochemical reaction tube, add 2a (5 mmol, 1.0 equiv.), cobalt iodide (0.5 mmol, 10 mol%), L18 (1 mmol, 20 mol%), sodium iodide (2 mmol, 40 mol%), Molecular sieve (250 mg), N,N-dimethylformamide (20 mL), iron electrode as anode, nickel foam electrode as cathode (4×4 cm ² ) were installed in the reaction tube. The reaction device was placed at room temperature and stirred for 30 minutes. After stirring, 6 mA was turned on 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.

Method D: Cross coupling (5 mmol)

Reaction procedure (5 mmol scale): In a glove box, add a stirrer to an electrochemical reaction tube, 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%), sodium iodide (2 mmol, 40 mol%), Molecular sieve (250 mg), N,N-dimethylacetamide (20 mL), iron electrode as anode, nickel foam electrode as cathode (4×4 cm ² ) were installed in the reaction tube. The reaction device was placed at room temperature and stirred for 30 minutes. After stirring, 6 mA was turned on and the reaction was carried out for 72 hours. After the reaction, 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.

Example 1

(4a) (57.6 mg, 78%) was obtained by method A, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.32 (d, J = 8.8 Hz, 2H), 8.04 (d, J = 8.8 Hz, 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, CDCl ₃ )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,CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane: isopropanol = 90:10, flow rate 1 mL/min, T = 25 ° C, λ = 254 nm): tR = 9.199 min ( Small), tR＝13.320min(Large).

(4a) (1.11 g, 90%) was obtained by method C with an enantiomeric ratio of 95:5 and was identified by chiral HPLC.

Example 2

Obtained 4b (1.11 g, 90%) by method A. ¹ H NMR (400MHz, CDCl ₃ ) δ 8.27 (d, J = 8.8 Hz, 2H), 7.96 (d, J = 8.8 Hz, 2H), 7.72 ( s,2H),7.28–7.05(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, CDCl ₃ )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, 1330,1278,1229,1186.1160,1100,1049,956,922,895,827,793,741,714,687,496 cm ^-1 .HRMS (DART) calculated for C ₃₈ H ₃₄ O ₄ N[M+NH ₄ ] ⁺ :568.2482, experimental value:568.2486.[α] ^29.3 =32.78 (c=1.0, CHCl ₃ ). 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 °C, λ = 254 nm): tR = 9.035 min (small), tR = 11.565 min (large).

Example 3

4c (85.5 mg, 89%) was obtained by method A. The starting material was 2c, mp = 187.7-189.1 °C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 8.4 Hz, 2H), 7.86-7.72 (m, 4H), 7.35 (d, J = 7.2 Hz, 4H), 7.25 (d, J = 8.4 Hz, 2H), 7.17-6.98 (m, 4H), 6.86 (d, J = 7.6 Hz, 4H), 6.92-6.81 (m, 4H), 6.80-6.70 (m, 2H) 6.40 (d, J = 7.6 Hz, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ165.4,150.6,140.7,140.6,140.2,135.6,132.1,129.3,129.0,128.6,128.0,127.9,127.5,126.8,126.8,126.7,125.9,125.6,121.4. 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 O ₄ N[M+NH ₄ ] ⁺ :664.2482 Exp. value:664.2487.[α] ^27.3 =-23.26 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 95:5, identified by chiral HPLC (Daicel IG column, n-hexane: isopropanol = 90:10, flow rate 0.7 mL/min, T = 25°C, λ = 214 nm): tR = 35.81 min (small), tR = 39.01 min (large).

Example 4

4d (62.9 mg, 76%) was obtained by method A. The starting material was 2d. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.30 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 8.4 Hz, 2H), 7.30-7.05 (m, 10H), 6.96 (d, J = 9.2 Hz, 2H), 6.72 (d, J = 7.6 Hz, 4H), 3.93 (s, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₆ [M+H] ⁺ :555.1802 Experimental value:555.1805.[α] ^29.8 =44.96 (c=0.8, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane: isopropanol = 80:20, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 9.461min (small), tR = 16.322min (large).

Example 5

4e (60.5 mg, 61%) was obtained by method A. The starting material was 2e. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.29 (d, J = 8.4 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.27-7.18 (m, 6H), 7.15-7.05 (m, 4H), 6.95 (d, J = 9.6 Hz, 2H), 6.72 (d, J = 8.0 Hz, 4H), 5.93-5.80 (m, 2H), 5.13-4.99 (m, 4H), 4.11 (t, J = 6.4 Hz, 4H), 2.28 (dd, J = 14.8, 7.2 Hz, 4H), 2.01-1.77 (m, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ165.5,158.8,150.8,141.1,137.8,137.1,129.3,129.1,128.3,127.2,126.9,125.6,124.4,121.5,120.1,115.5,106.7,67.4,30.2,28.4.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 O ₆ [M+H] ⁺ :685.2561 Exp. value:685.2555.[α] ^28.6 =26.59 (c=1.0, CHCl ₃ ). Enantiomer ratio =96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol=90:10, flow rate 1mL/min, T=25°C, λ=254nm): tR=7.716min (small), tR=8.982min (large).

Example 6

4f (66.7 mg, 86%) was obtained by method A. The starting material was 2f. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.24 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.8 Hz, 2H), 7.86 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.23-7.14 (m, 4H), 7.11-7.04 (m, 2H), 6.98 (s, 2H), 6.63 (d, J = 7.6 Hz, 4H), 2.26 (s, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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)理论值C ₃₆ H ₂₇ O ₄ [M+H] ⁺ :523.1904实验值:523.1906.[α] ^26.4 =46.09 (c=1.0, CHCl ₃ ). 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°C, λ = 254 nm): tR = 21.870 min (small), tR = 26.988 min (large).

Example 7

4 g (49.1 mg, 62%) of starting material was obtained by method A, which was 2 g. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.29 (d, J = 8.4 Hz, 2H), 8.05 (d, J = 8.4 Hz, 2H), 7.97 (dd, J = 9.2, 5.6 Hz, 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 (101 MHz, CDCl ₃ )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). ¹⁹ F NMR (376MHz, CDCl ₃ )δ-111.57. IR (neat): 2972, 1738, 1628, 1593, ¹⁵¹⁰ , 1489, 1442, 1313, 1231, 1181, 1121, 1092, 952, 843, 741, 720, 687, 531, 484, 433 cm -1 . HRMS (DART) theoretical value C ₃₄ H ₂₁ O ₄ F ₂ [M+H] ⁺ : 531.1402 experimental value: 531.1400. [α] ^29.0 ＝23.40 (c＝0.9, CHCl ₃ ). Enantiomeric ratio＝95:5, identified by chiral HPLC (Chiralpak OJ (4.6*250mm), CO ₂ :IPA=85:15, flow rate 1.3mL/min, T=26℃, λ=214nm):tR=13.859min(large), tR=17.425min(small).

Example 8

4h (55.1 mg, 58%) was obtained by method A. The starting material was 2h. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.36–8.21 (m, 4H), 7.40 (d, J=6.8 Hz, 2H), 7.25–7.04 (m, 10H), 6.62 (d, J=8.0 Hz, 4H), 3.27–3.04 (m, 4H), 1.88–1.75 (m, 8H), 1.54–1.38 (m, 4H), 0.96 (t, J=6.8 Hz, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₄ [M+H] ⁺ :635.3156 Experimental value:635.3156.[α] ^29.8 =28.03 (c=1.0, CHCl ₃ ). Enantiomer ratio = 95:5, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 7.759min (small), tR = 9.244min (large).

Example 9

4i (59.0 mg, 71%) was obtained by method A. The starting material was 2i, mp = 125.4-127.6 °C. ¹ H NMR (400 MHz, CD ₂ Cl ₂ ) δ 8.41 (d, J = 9.2 Hz, 2H), 8.17 (d, J = 9.2 Hz, 2H), 7.20-7.00 (m, 8H), 6.85 (d, J = 7.6 Hz, 2H), 6.66 (d, J = 8.4 Hz, 2H), 6.59 (d, J = 7.6 Hz, 4H), 3.97 (s, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CD ₂ Cl ₂ )δ165.6,155.4,150.7,139.9,133.9,129.1,127.6,127.4,127.1,125.6,125.2,122.2,121.3,119.2,105.9,55.8.IR(neat):1722,1591,1489,1461,1408,1379,1320,1259,1187,1160,1104,931,834,766,739,687cm ^-1 .HRMS(DART)theoretical value for C ₃₆ H ₃₀ O ₆ N[M+H] ⁺ :572.2068 Observation value:572.2066.[α] ^28.9 =49.13 (c=0.6, CHCl ₃ ). Enantiomer ratio = 98:2, identified by chiral HPLC (Chiralpak IA column, n-hexane: isopropanol = 90:10, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 18.271 min (large), tR = 24.085 min (small).

Example 10

4j (56.0 mg, 72%) was obtained by method A. The starting material was 2j. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.17 (s, 2H), 8.12 (d, J = 8.4 Hz, 2H), 7.60 (t, J = 7.6 Hz, 2H), 7.30-7.17 (m, 8H), 7.14-7.07 (m, 2H), 6.70 (d, J = 8.0 Hz, 4H), 2.85 (s, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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)理论值C ₃₆ H ₂₇ O ₄ [M+H] ⁺ :523.1904实验值:523.1903.[α] ^30.4 =34.82 (c=0.9, CHCl ₃ ). 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°C, λ = 254 nm): tR = 6.342 min (large), tR = 8.264 min (small).

Embodiment 11

4k (69.6 mg, 72%) was obtained by method A. The starting material was 2k, mp = 193.5-195.5°C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.12 (s, 2H), 8.03 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 7.6 Hz, 4H), 7.65-7.07 (m, 12H), 7.13-6.96 (m, 6H), 6.16 (d, J = 8.4 Hz, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ166.6,150.2,140.9,137.3,135.0,133.6,132.0,131.8,129.7,129.0,129.0,128.6,128.2,127.8,127.7,127.5,127.2,121.1. 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 O ₄ [M+H] ⁺ :647.2217 Experimental value:647.2219.[α] ^29.2 =15.98 (c=1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 4.724min (small), tR = 8.120min (large).

4k (1.17 g, 73%) was obtained by method C. The starting material was 2k. The enantiomeric ratio = 95:5, identified by chiral HPLC.

Example 12

41 (67.9 mg, 65%) was obtained by method A. The starting material was 21. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.07 (s, 2H), 7.98 (d, J = 8.0 Hz, 2H), 7.65-7.45 (m, 8H), 7.45-7.28 (m, 6H), 7.10-6.90 (m, 6H), 6.12 (d, J = 7.6 Hz, 4H), 2.74 (q, 7.2 Hz, 4H), 1.31 (t, J = 7.2 Hz, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₄ N[M+H] ⁺ :720.3108 Experimental value:720.3106.[α] ^26.2 =58.37 (c=1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 11.817min (small), tR = 14.752min (large).

Example 13

4m (69.2 mg, 63%) was obtained by method A. The starting material was 2m. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05 (s, 2H), 7.96 (d, J = 8.0 Hz, 2H), 7.64-7.43 (m, 8H), 7.45-7.25 (m, 6H), 7.05-6.90 (m, 6H), 6.10 (d, J = 7.6 Hz, 4H), 2.66 (t, J = 7.6 Hz, 4H), 1.84-1.50 (m, 4H), 0.98 (t, J = 7.2 Hz, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ166.7,150.3,142.3,138.3,137.4,134.9,133.6,132.0(2C),129.6,128.9,128.7,128.1,127.7,127.6,127.1,125.5,121.2,37.8,24.7,13.9. 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 O ₄ N[M+H] ⁺ :748.3421 Experimental value:748.3420.[α] ^30.3 =-1.84 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane: isopropanol = 95:5, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 7.690min (small), tR = 9.609min (large).

Embodiment 14

4n (72.1 mg, 66%) was obtained by method A. The starting material was 2n. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05 (s, 2H), 7.96 (d, J = 8.4 Hz, 2H), 7.68-7.44 (m, 8H), 7.41-7.30 (m, 6H), 7.07-6.90 (m, 6H), 6.05 (d, J = 8.0 Hz, 4H), 3.03-2.93 (m, 2H), 1.31 (d, J = 6.8 Hz, 12H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ166.7,150.3,148.4,138.5,137.4,134.9,133.6,132.0(2C),129.5,129.0,128.9,128.1,127.7,127.6,127.1,126.7,125.4,121.2,34.0,24.2,24.1.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 O ₄ [M+H] ⁺ :731.3156 Experimental value:731.3155.[α] ^26.8 =3.85 (c=1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 6.738min (small), tR = 10.526min (large).

Embodiment 15

4o (72.9 mg, 65%) was obtained by method A. The starting material was 2o. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.10 (s, 2H), 8.00 (d, J = 8.0 Hz, 2H), 7.71-7.34 (m, 14H), 7.10-7.34 (m, 6H), 6.08 (d, J = 6.8 Hz, 4H), 1.42 (s, 18H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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(2C),121.2,34.7,31.5.IR(neat):2958,1747,1590,1490,1257,1222,1186,1159,1114,1084,1064,1022,975,899,833,746,687,607,564,508cm ^-1 .HRMS(DART)理论值C ₅₄ H ₅₀ O ₄ N[M+NH ₄ ] ⁺ :776.3734 Experimental value:776.3733.[α] ^28.9 =4.19 (c=1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 5.461min (small), tR = 8.355min (large).

Example 16

4p (63.6 mg, 60%) was obtained by method A. The starting material was 2p. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.06 (s, 2H), 7.98 (d, J = 8.4 Hz, 2H), 7.67-7.46 (m, 8H), 7.46-7.35 (m, 2H), 7.12-6.94 (m, 10H), 6.19 (d, J = 8.0 Hz, 4H), 3.88 (s, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₆ N[M+NH ₄ ] ⁺ :724.2694 Experimental value:724.2694.[α] ^27.3 =-1.05 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Daicel Chiralpak ADH column, n-hexane: isopropanol = 90:10, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 11.948 min (small), tR = 16.206 min (large).

4q (79.8 mg, 67%) was obtained by method A. The starting material was 2q. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.16 (s, 2H), 8.04 (d, J = 8.4 Hz, 2H), 7.83-7.33 (m, 24H), 7.10-6.94 (m, 6H), 6.19 (d, J = 8.0 Hz, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₄ Na[M+Na] ⁺ :821.2662 Exp. value:821.2661.[α] ^29.5 =-45.66 (c=1.0, CHCl ₃ ). Enantiomer ratio = 99:1, identified by chiral HPLC (Daicel IG column, n-hexane:isopropanol = 90:10, flow rate 0.7 mL/min, T = 25°C, λ = 214 nm): tR = 24.95 min (small), tR = 35.90 min (large).

Embodiment 17

4r (61.1 mg, 60%) was obtained by method A. The starting material was 2r. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.94 (s, 2H), 7.89 (d, J = 8.0 Hz, 2H), 7.57-7.28 (m, 6H), 7.40 (d, J = 8.4 Hz, 2H), 7.34-7.28 (m, 2H), 7.15-7.06 (m, 4H), 7.01-6.85 (m, 6H), 6.03 (d, J = 7.6 Hz, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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, CDCl ₃ )δ-111.54. IR (neat): 2972, 1743, 1591, 1510, 1489, 1258, 1221, 1185, 1158, 1086, 976, 901, 836, 743, 687, 598, 548, 511 cm ^-1 HRMS (DART) theoretical value _{C 46} H ₃₂ O ₄ NF ₂ [M+NH ₄ ] ⁺ : 700.2294 experimental value: 70.2296. [α] ^28.5 ＝20.87 (c＝1.0, CHCl ₃ ). Enantiomer ratio＝96:4, identified by chiral HPLC (Chiralpak IA column, hexane: isopropanol = 95:5, flow rate 1 mL/min, T = 25 ° C, λ = 254 nm): tR = 10.123 min (small), tR = 17.499 min (large).

Embodiment 18

4s (55.3 mg, 52%) was obtained by method A. The starting material was 2s. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.02 (s, 2H), 7.98 (d, J = 8.0 Hz, 2H), 7.64-7.52 (m, 6H), 7.51-7.36 (m, 8H), 7.09-6.94 (m, 6H), 6.11 (d, J = 8.0 Hz, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₄ Cl ₂ [M+H] ⁺ :715.1437 Experimental value:715.1440.[α] ^30.4 =-6.43 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (ChiralpakIA column, n-hexane: isopropanol = 90:10, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 6.762min (small), tR = 8.297min (large).

Embodiment 19

4t (63.8 mg, 58%) was obtained by method A. The starting material was 2t. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.15–7.96 (m, 8H), 7.77 (d, J=8.0 Hz, 4H), 7.65–7.58 (m, 2H), 7.56–7.40 (m, 4H), 7.10–6.94 (m, 6H), 6.13 (d, J=8.0 Hz, 4H), 2.66 (s, 6H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )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 O ₆ N[M+NH ₄ ] ⁺ :748.2694 Experimental value:748.2697.[α] ^25.3 =-33.76 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 98:2, identified by chiral HPLC (Chiralpak IA column, n-hexane: isopropanol = 80:20, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 14.571min (small), tR = 24.868min (large).

Embodiment 20

4u (73.7 mg, 65%) was obtained by method A. The starting material was 2u. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.19 (d, J = 8.0 Hz, 4H), 8.10 (s, 2H), 8.03 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.0 Hz, 4H), 7.65-7.58 (m, 2H), 7.55-7.40 (m, 4H), 7.10-6.96 (m, 6H), 6.14 (d, J = 7.6 Hz, 4H), 3.97 (s, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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):1718,1590,1488,1433,1275,1223,1183,1159,1105,1019,975,902,859,775,746,710,687,602,486cm ^-1 HRMS(DART)theoretical value C ₅₀ H ₃₈ O ₈ N[M+NH ₄ ] ⁺ :780.2592 Exp. value:780.2595.[α] ^28.1 =-28.99 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 98:2, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 18.151 min (small), tR = 23.833 min (large).

Embodiment 21

4v (64.4 mg, 55%) was obtained by method A. The starting material was 2v. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.10 (s, 2H), 8.04 (d, J = 8.4 Hz, 2H), 7.83-7.74 (s, 8H), 7.64 (t, J = 7.2 Hz, 2H), 7.58-7.42 (m, 4H), 7.12-6.90 (m, 6H), 6.09 (d, J = 7.6 Hz, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ166.2,150.0,144.6,136.0,135.4,133.5,132.2,131.3,130.1(q,J＝32.3Hz),130.0,129.4,129.1,128.4,128.3,127.8,127.5,125.8,125.6(q , J=4.0Hz), 124.2 (q, J=275.7Hz), 120.7. ¹⁹ F NMR (376MHz, CDCl ₃ )δ-62.42. IR (neat): 2986, 1744, 1591, 1490, 1404, 1322, 1258, 1223, 1160, 1107, 1063, 1018, 901, 850, 744, 687, 612, 504 cm ^{-1 .} HRMS (DART) theoretical value C ₄₈ H ₂₉ O ₄ F ₄ [M+H] ⁺ : 783.1965 experimental value: 783.1955. [α] ^29.9 = 4.51 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 98:2, identified by chiral high performance liquid chromatography (Chiralpak IA column, hexane: isopropanol = 95:5, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 6.253min (small), tR = 8.122min (large).

Example 22

4w (81.5 mg, 68%) was obtained by method A. The starting material was 2w. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.18 (s, 2H), 8.04 (d, J = 8.0 Hz, 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 = 7.6 Hz, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₄ [M+H] ⁺ :799.2843 Experimental value:799.2843.[α] ^25.81 =-9.66 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane: isopropanol = 90:10, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 5.893 min (small), tR = 7.831 min (large).

Embodiment 23

4x (65.9 mg, 62%) of starting material was obtained by method A as 2x. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.12 (s, 2H), 8.02 (d, J = 8.0 Hz, 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 = 8.0 Hz, 4H), 3.85 (s, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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):1742,1588,1487,1455,1262,1233,1184,1158,1094,1044,992,956,879,785,743,688,556,492,468cm ^-1 .HRMS(DART)theoretical value C ₄₈ H ₃₈ O ₆ N[M+NH ₄ ] ⁺ :724.2694 Experimental value:724.2691.[α] ^27.7 =17.83 (c=1.0, CHCl ₃ ). Enantiomer ratio =97:3, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol=90:10, flow rate 1mL/min, T=25°C, λ=254nm): tR=6.955min (small), tR=10.594min (large).

Embodiment 24

4y (84.1 mg, 78%) was obtained by method A. The starting material was 2y. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.07 (s, 2H), 8.02 (d, J = 8.4 Hz, 2H), 7.70-7.56 (m, 2H), 7.51-7.41 (m, 4H), 7.24-6.83 (m, 12H), 6.23 (d, J = 7.6 Hz, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ166.1,164.2(d,J＝13.1Hz),161.7(d,J＝13.1Hz),150.1,143.9(t,J＝10.1Hz),135.4,135.1,133.4,132.3,131.0,129.9,129.2,128.3,128.0,127 .4,125.8,120.7,112.1(dd,J＝19.2Hz,8.1Hz),103.2(t,J＝25.3Hz) ¹⁹ FNMR(376MHz, CDCl ₃ )δ-109.26. IR (neat): 2963, 1743, 1590, 1490, 1253, 1185, 1159, 1088, 1023, 900, 831, 739, 686, 600, 578, 507 cm ^-1 . HRMS (DART) theoretical value _{C 46} H ₃₀ O ₄ NF ₄ [M+NH ₄ ] ⁺ : 736.2105 experimental value: 736.2106. [α] ^30.1 ＝17.01 (c＝1.0, CHCl ₃ ). Enantiomer ratio＝97:3, identified by chiral high performance liquid chromatography (Chiralpak IA column, hexane: isopropanol = 95:5, flow rate 1 mL/min, T = 25 ° C, λ = 254 nm): tR = 6.003 min (small), tR = 10.431 min (large).

Embodiment 25

4z (70.4 mg, 63%) was obtained by method A. The starting material was 2z. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.30–8.10 (m, 4H), 8.12–7.80 (m, 10H), 7.69–7.41 (m, 10H), 7.10–6.83 (m, 6H), 6.11 (d, J=7.2 Hz, 4H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )δ166.7,150.2,138.3,137.2,135.2,133.6,133.4,132.7,132.0,131.9,130.1,129.0,128.2,128.2(2C),127.9,127.8(2C),127.6,127.4,127.2,126.6,126.2,125.5,121.0.IR(neat):1751,1587,1488,1258,1238,1183,1159,1129,1083,993,897,858,820,742,688,506,476cm ^-1 .HRMS(DART)理论值C ₅₄ H ₃₈ O ₄ N[M+NH ₄ ] ⁺ :764.2795 Exp. value:764.2798.[α] ^26.7 =-55.87 (c=1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol = 90:10, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 9.465 min (small), tR = 10.551 min (large).

Embodiment 26

4aa (64.0 mg, 65%) was obtained by method A. The starting material was 2aa. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.95–7.85 (m, 4H), 7.51 (t, J=7.2 Hz, 2H), 7.43–7.28 (m, 4H), 7.22–7.12 (m, 4H), 7.10–7.02 (m, 2H), 6.53 (d, J=8.0 Hz, 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{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₄ [M+H] ⁺ :655.2843 Experimental value:655.2846.[α] ^25.5 =48.59 (c=1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral HPLC (Chiralpak IA column, n-hexane:isopropanol = 95:5, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 4.730min (small), tR = 5.270min (large).

Embodiment 27

4ab (56.1 mg, 75%) was obtained by method A. The starting material was 2ab, mp = 163.5-164.8 °C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.00 (d, J = 3.2 Hz, 2H), 8.58 (d, J = 9.2 Hz, 2H), 8.36 (d, J = 9.2 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.36-7.20 (m, 6H), 7.16-7.09 (m, 2H), 6.73 (d, J = 8.0 Hz, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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):2922,1717,1588,1564,1489,1454,1404,1383,1323,1260,1239,128,1186,1100,1064,1024,927,899,844,786,738,685,554,496,462cm ^-1 . HRMS(DART)theoretical value C ₃₂ H ₂₁ O ₄ N ₂ [M+NH ₄ ] ⁺ :497.1496 Experimental value:497.1491.[α] ^25.9 =45.97 (c=1.0, CHCl ₃ ). Enantiomer ratio = 93:7, identified by chiral HPLC (Daicel Chiralpak ODH column, n-hexane: isopropanol = 80:20, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 13.933 min (large), tR = 16.187 min (small).

Embodiment 28

7a (106.6 mg, 72%) was obtained by method B. The starting materials were 1a and 6a. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.18 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.84-7.75 (m, 2H), 7.53-7.44 (m, 1H), 7.33-7.06 (m, 11H), 7.01 (d, J = 8.4 Hz, 1H), 6.95-6.83 (m, 2H), 6.78 (d, J = 7.6 Hz, 2H), 4.90 (s, 2H), 4.86 (s, 2H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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):2926,1716,1620,1591,1504,1453,1377,1327,1272,1232,1122,1081,1046,1018,961,915,868,805,766,735,69 6,590,563,486,464,433cm ^-1. HRMS (DART) theoretical value C ₃₅ H ₃₀ O ₃ N ₂ [M+NH ₄ ] ⁺ :512.2220 experimental value:512.2216. [α] ^27.5 =7.56 (c=1.0, CHCl ₃ ). 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°C, λ = 254 nm): tR = 7.105 min (small), tR = 7.813 min (large).

7a (1.89 g, 76%) was obtained by method D. The starting materials were 1a and 6a, the enantiomeric ratio was 95:5, and it was identified by chiral HPLC.

Embodiment 29

7b (126.7 mg, 79%) was obtained by method B. The starting materials were 1a and 6b. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.16 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.55–7.43 (m, 2H), 7.35–6.97 (m, 9H), 6.93–6.84 (m, 4H), 6.77 (d, J = 7.6 Hz, 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, CDCl ₃ ) 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),1 27.7,127.4,126.7,126.6,126.3,125.4,125.2, 123.9,122.9,115.5,71.0,66.7,15.4,9.0.IR(neat):3030,1703,1594,1498,1454,1377,1322,1271,1232,1121,1083,1045,1024,967,904,865,8 22,765,732,694,627,462cm ^-1. HRMS (DART) theoretical value C ₃₈ H ₃₀ O ₃ Na [M + Na] ⁺ : 557.2087 experimental value: 557.2094. [α] ^23.4 = -1.11 (c = 1.0, CHCl ₃ ). 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 ° C, λ = 254 nm): tR = 6.523 min (small), tR = 7.796 min (large).

Embodiment 30

7c (134.0 mg, 77%) was obtained by method B. The starting materials were 1a and 6c. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.17 (d, J = 8.8 Hz, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 9.2 Hz, 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, CDCl ₃ ) δ167.7,152.7,143.2,137.6,137.4,135.5,135.2,133.1,132.7,129.4,129.0,128.2(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):3062,2922,2850,2117,1705,1595,1498,1451,1377,1326,1272,1233,1121,1075,1027 ,907,873,822,797,766,732,695cm ^-1. HRMS (DART) theoretical value C ₄₁ H ₃₆ O ₃ Na [M + Na] ⁺ : 599.2557 experimental value: 599.2559. [α] ^26.9 = -1.84 (c = 1.0, CHCl ₃ ). 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 ° C, λ = 254 nm): tR = 5.664 min (small), tR = 6.185 min (large).

Embodiment 31

7d (112.2 mg, 66%) was obtained by method B. The starting materials were 1a and 6d. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.10 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.74-7.66 (m, 2H), 7.44-7.38 (m, 1H), 7.22-6.99 (m, 10H), 6.92 (d, J = 8.8 Hz, 1H), 6.85-6.79 (m, 2H), 6.71 (d, J = 7.2 Hz, 2H), 5.10 (s, 2H), 4.82-4.72 (m, 4H), 2.00 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ171.0,167.5,153.6,137.3,136.9,135.4,135.2,133.8,133.0,131.0,129.4,129.0,128.7,128.2(3C),128.1,128.0,127.8(2C),127.7,127. 5,126.7(2C),126.4,12 5.6,122.9,115.5,70.8,66.7,66.6,21.1.IR(neat):2946,1722,1618,1593,1499,1454,1374,1319,1268,1237,1131,1074,1023,984,906,857,80 5,734,695,628,460cm ^-1. HRMS (DART) theoretical value C ₃₈ H ₃₄ O ₅ N [M + NH ₄ ] ⁺ : 584.2431 experimental value: 584.2424. [α] ^28.0 = -0.98 (c = 1.0, CHCl ₃ ). 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 ° C, λ = 254 nm): tR = 13.323 min (small), tR = 15.302 min (large).

Embodiment 32

7e (102.0 mg, 65%) was obtained by method B. The starting materials were 1a and 6e. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.18 (d, J = 8.8 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.8 Hz, 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 = 17.6 Hz, 1H), 5.25 (d, J = 10.8 Hz, 1H), 5.02-4.67 (m, 4H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ167.6,153.4,137.4,136.9,135.4,135.2,133.7,133.0(2C),129.5,129.1,129.0,128.2(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):2867,2122,1704,1620,1591,1498,1454,1377,1327,1271,1233,1121,1077,1044,988,905,829,797,7 66,735,696,463cm ^-1. HRMS (DART) theoretical value C ₃₇ H ₂₉ O ₃ [M+H] ⁺ :521.2108 experimental value:521.2111. [α] ^26.2 =-10.69 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 95:5, identified by chiral HPLC (Daicel Chiralpak ADH column, n-hexane: isopropanol = 90:10, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 6.932 min (small), tR = 7.750 min (large).

Embodiment 33

7f (121.5 mg, 77%) was obtained by method B. The starting materials were 1a and 6f, mp = 135.2-137.5 °C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.16 (d, J = 8.8 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 9.2 Hz, 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 (101 MHz, CDCl ₃ )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),126.3,123.5,119.3,116.1,106.0,71.2 ,66.7,55.3.IR(neat):2857,2320,1703,1624,1591,1503,1453,1378,1324,1272,1241,1168,1115,1077,1053,1024,965,908,849,822,796,766, 736,696,633,608,569,522,494,458,424cm ^-1. HRMS (DART) theoretical value C ₃₆ H ₂₈ O ₄ [M+H] ⁺ :524.1982 experimental value:524.1976. [α] ^26.5 =8.40 (c=1.0, CHCl ₃ ). Enantiomer ratio =93:7, identified by chiral HPLC (Daicel Chiralpak ODH column, n-hexane:isopropanol=90:10, flow rate 1mL/min, T=25°C, λ=254nm): tR=8.053min (small), tR=9.451min (large).

Embodiment 34

7 g (90.3 mg, 54%) was obtained by method B. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.17 (d, J = 8.8 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.4 Hz, 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 (101 MHz, CDCl ₃ )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. 6,123.8,119.4,119.2,116.2 ,106.0,105.9,71.2,66.5,55.4,55.3.IR(neat):2934,2119,1701,1620,1596,1502,1475,1454,1375,1335,1274,1232,1195,1168,1121,1074,10 27,853,822,788,734,696cm ^-1. HRMS (DART) theoretical value C ₃₇ H ₃₁ O ₅ [M+H] ⁺ :555.2166 experimental value:555.2169. [α] ^27.7 =4.23 (c=1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane: isopropanol = 90:10, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 10.972min (small), tR = 13.190min (large).

Embodiment 35

7h (88.5 mg, 53%) was obtained by method B. The starting materials were 1a and 6g, mp = 148.5-151.3 °C. ¹ H NMR (400 MHz, CDCl ₃ )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),7.58–7.4 8(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(101 MHz, CDCl ₃ )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):2947,2119,1701,1620,1596,1502,1475,1454,1375,1274,1232,1195,1168,1121,1074,1027 ,853,822,788,734,696cm ^-1. HRMS (DART) theoretical value C ₃₇ H ₂₉ O ₅ [M+H] ⁺ :553.2010 experimental value:553.2007. [α] ^24.0 =-7.59 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 95:5, identified by chiral HPLC (Daicel Chiralpak ADH column, n-hexane: isopropanol = 80:10, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 13.560 min (small), tR = 20.140 min (large).

Embodiment 36

7i (110.2 mg, 72%) was obtained by method B. The starting materials were 1c and 6a. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.16–8.15 (m, 2H), 7.84 (d, J=8.8 Hz, 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=7.2 Hz, 2H), 4.96 (s, 2H), 4.90 (s, 2H), 2.87 (s, 3H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )δ167.8,153.3,137.6,135.5,135.2,134.5,134.4,134.2,133.1,129.2,129.1,128.6,128.4,128.2(2C),127.9,127.8,127.5,127.4,126.7(2C) ),126.4,126.3,125.2,124.2,123.6,123.1,115.3 ,70.8,66.6,19.6.IR(neat):2857,2320,1703,1624,1591,1503,1453,1378,1324,1272,1241,1168,1116,1077,1053,1024,965,908,849,822,796 ,766,736,696,633,608,569,522,494,458,424cm ^-1. HRMS (DART) theoretical value C ₃₆ H ₂₉ O ₃ [M+H] ⁺ :509.2111 experimental value:509.2108. [α] ^24.5 =8.78 (c=1.0, CHCl ₃ ). Enantiomer ratio = 95:5, identified by chiral HPLC (Daicel Chiralpak ADH column, n-hexane: isopropanol = 95:5, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 8.426 min (small), tR = 9.027 min (large).

Embodiment 37

7j (114.3 mg, 75%) was obtained by method B. The starting materials were 1b and 6a. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.10 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.84-7.60 (m, 3H), 7.38-6.98 (m, 12H), 6.96-6.88 (m, 2H), 6.78 (d, J = 7.2 Hz, 2H), 4.92 (s, 2H), 4.84 (s, 2H), 2.19 (s, 3H). ¹³ C NMR (101 MHz, CDCl ₃ )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):3031,2119,1705,1622,1593,1507,1453,1376,1316,1267,1235,1121,1072,1047,1017,968,90 7,844,806,733,695cm ^-1. HRMS (DART) theoretical value C ₃₆ H ₂₉ O ₃ [M+H] ⁺ :509.2111 experimental value:509.2116. [α] ^26.8 =11.65 (c=1.0, CHCl ₃ ). Enantiomer ratio = 94:6, identified by chiral high performance liquid chromatography (Daicel IG column, n-hexane:isopropanol = 90:10, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 7.647min (small), tR = 8.424min (large).

Embodiment 38

7k (111.3 mg, 71%) was obtained by method B. The starting materials were 1d and 6a. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05 (dd, J = 15.6 Hz, 8.8 Hz, 2H), 7.72 (d, J = 8.8 Hz, 2H), 7.25-7.01 (m, 10H), 6.97-6.78 (m, 4H), 6.71 (d, J = 7.2 Hz, 2H), 4.85 (s, 2H), 4.76 (s, 2H), 2.66 (s, 3H), 2.10 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ167.8,153.1,137.6,136.6,135.8,135.5,134.1(2C),133.5,132.7,130.9,129.1,129.0,128.8,128.2,128.1,127.9,127.7,127.4,126.7,12 6.4,125.3,125.2,124.9,123.9, 123.6,123.4,115.2,70.8,66.6,21.8,19.6.IR(neat):2926,1704,1621,1593,1507,1454,1371,1316,1268,1243,1131,1081,1056,1019,906,859 ,804,731,694,576,495,428cm ^-1. HRMS (DART) theoretical value C ₃₇ H ₃₁ O ₃ [M+H] ⁺ :523.2268 experimental value:523.2263. [α] ^28.0 =3.50 (c=1.0, CHCl ₃ ). Enantiomer ratio = 94:6, identified by chiral high performance liquid chromatography (DaicelIG column, n-hexane:isopropanol = 90:10, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 7.383min (small), tR = 8.310min (large).

Embodiment 39

7i (100.4 mg, 64%) was obtained by method B. The starting materials were 1 g and 6a. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.45 (d, J = 8.8 Hz, 1H), 8.16 (d, J = 8.8 Hz, 1H), 7.79 (d, J = 8.8 Hz, 2H), 7.34-7.07 (m, 10H), 7.03-6.89 (m, 3H), 6.84 (d, J = 7.6 Hz, 2H), 6.78 (d, J = 7.6 Hz, 2H), 4.91 (s, 2H), 4.86 (s, 2H), 4.02 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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):3032,2947,1722,1619,1592,1500,1455,1374,1319,1268,1238,1131,1073,1023,984,90 7,857,806,733,695,628cm ^-1. HRMS (DART) theoretical value C ₃₆ H ₂₉ O ₄ [M+H] ⁺ :525.2060 experimental value:525.2059. [α] ^25.4 =2.36 (c=1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Daicel IG column, n-hexane: isopropanol = 90:10, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 12.106min (large), tR = 14.020min (small).

Embodiment 40

7m (96.5 mg, 61%) was obtained by method B. The starting materials were 1f and 6a. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.19 (d, J = 8.8 Hz, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.33-7.09 (m, 11H), 7.01 (d, J = 8.4 Hz, 1H), 6.95-6.84 (m, 3H), 6.78 (d, J = 7.2 Hz, 2H), 4.91 (s, 2H), 4.85 (s, 2H), 3.88 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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),128.1,128.0,127.8,127.4,127.3,126.7,12 6.6,126.5,125.1,123.7,1 23.3,119.4,115.3,105.9,70.9,66.6,55.4.IR(neat):2946,1722,1618,1593,1499,1455,1373,1317,1268,1238,1131,1073,1022,984,906,857, 805,733,695,628,459cm ^-1. HRMS (DART) theoretical value C ₃₆ H ₂₈ O ₄ Na [M + Na] ⁺ : 547.1880 experimental value: 547.1887. [α] ^25.1 = 6.09 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Daicel (Chiralpak ODH column, n-hexane: isopropanol = 90:10, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 9.530min (small), tR = 10.549min (large).

Embodiment 41

7n (97.7 mg, 62%) was obtained by method B. The starting materials were 1e and 6a. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.84-7.75 (m, 3H), 7.34-6.99 (m, 11H), 6.93 (d, J = 4.8 Hz, 2H), 6.79 (d, J = 7.2 Hz, 2H), 6.51 (s, 1H), 4.92 (s, 2H), 4.86 (s, 2H), 3.36 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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, 126.5,125.1,124.2,123.7 ,123.1,120.1,115.2,106.1,70.9,66.67,55.0.IR(neat):2935,2117,1723,1621,1593,1507,1454,1377,1316,1267,1220,1179,1124,1071,1030 ,908,845,807,734,695cm ^-1. HRMS (DART) theoretical value C ₃₆ H ₂₉ O ₄ [M+H] ⁺ :525.2060 experimental value:525.2065. [α] ^27.1 =-2.38 (c = 1.0, CHCl ₃ ). Enantiomer ratio = 86:14, identified by chiral HPLC (Daicel Chiralpak ADH column, n-hexane: isopropanol = 90:10, flow rate 1 mL/min, T = 25°C, λ = 254 nm): tR = 8.876 min (large), tR = 10.466 min (small).

Embodiment 42

7o (101.6 mg, 59%) was obtained by method B. The starting materials were 1i and 6a. ¹ H NMR (400 MHz, CDCl ₃ )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,2 H),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, CDCl ₃ )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),128.1,127.9,127.7,127.4,127.2,12 6.7(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):2940,2117,1701,1619,1502,1463,1377,1332,1272,1233,1177,1122,107 3,1049,1017,909,855,805,733,695cm ^-1. HRMS (DART) theoretical value C ₄₀ H ₃₅ O ₄ [M+H] ⁺ :579.2530 experimental value:579.2521. [α] ^27.4 =2.94 (c=1.0, CHCl ₃ ). Enantiomer ratio = 95:5, identified by chiral HPLC (Daicel Chiralpak ODH column, n-hexane: isopropanol = 90:10, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 6.960min (large), tR = 7.739min (small).

Embodiment 43

7o (122.7 mg, 72%) was obtained by method B. Starting materials were 1h and 6a, mp = 133.7-135.4 °C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.12 (d, J = 8.8 Hz, 1H), 8.00 (s, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.70 (d, J = 7.2 Hz, 2H), 7.55 (d, J = 7.6 Hz, 2H), 7.46-6.92 (m, 15H), 6.83 (d, J = 3.2 Hz, 2H), 6.68 (d, J = 7.6 Hz, 2H), 4.82 (s, 2H), 4.77 (s, 2H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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),128.5,128.3,128.2,128.1,127.9,127.8,12 7.5,127.0,126.8,126.6,126.4,125.8,125.2 ,123.8,123.0,115.3,71.0,66.8.IR(neat):1720,1620,1592,1495,1451,1374,1332,1283,1246,1228,1148,1085,1056,1021,914,890,837,801, 760,725,691,609,588,570,500,459,432cm ^-1. HRMS (DART) theoretical value C ₄₀ H ₃₅ O ₄ [M+H] ⁺ :571.2268 experimental value:571.2265. [α] ^27.9 =5.86 (c=1.0, CHCl ₃ ). Enantiomer ratio = 96:4, identified by chiral high performance liquid chromatography (Daicel Chiralpak ODH column, n-hexane: isopropanol = 90:10, flow rate 1mL/min, T = 25°C, λ = 254nm): tR = 10.511min (small), tR = 11.709min (large).

Example 44: Ligand Screening

^α Reaction 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 sieves (70 mg) and N,N-dimethylformamide (5 mL) were used as the reaction solvent. The reaction was carried out at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and nickel foam as the cathode at a constant current of 1 mA for 24 hours. The conversion rate and yield were determined by hydrogen nuclear magnetic resonance spectroscopy with mesitylene as the internal standard. The ee value of the product was determined by chiral HPLC.

Example 45: Cathode Screening ^a

^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 sieves (70 mg) and N,N-dimethylformamide (5 mL) were used as the reaction solvent. The reaction was carried out at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and a constant current of 1 mA for 24 hours. The conversion rate and yield were determined by hydrogen nuclear magnetic resonance spectroscopy with mesitylene as the internal standard. The ee value of the product was determined by chiral HPLC.

Example 46: Electrolyte Screening ^a

^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 sieves (70 mg) and N,N-dimethylformamide (5 mL) were used as the reaction solvent. The reaction was carried out at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and stainless steel as the cathode at a constant current of 1 mA for 24 hours. The conversion rate and yield were determined by hydrogen nuclear magnetic resonance spectroscopy with mesitylene as the internal standard. The ee value of the product was determined by chiral HPLC.

Table S4 Screening of Solvent ^a

^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 sieves (70 mg) and solvent (5 mL) were used as reaction solvents. Electrolysis was carried out at room temperature in an IKA2.0 electrochemical reactor with iron as anode and stainless steel as cathode at a constant current of 1 mA for 24 hours. The conversion rate and yield were determined by H NMR with mesitylene as internal standard. The ee value of the product was determined by chiral HPLC.

Example 47: Co catalyst screening ^a

^aReaction 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 sieves (70 mg) and N,N-dimethylformamide (5 mL) were used as the reaction solvent. The reaction was carried out at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and stainless steel as the cathode at a constant current of 1 mA for 24 hours. The conversion rate and yield were determined by hydrogen nuclear magnetic resonance spectroscopy with mesitylene as the internal standard. The ee value of the product was determined by chiral HPLC.

Example 48: Anode Screening ^a

^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 sieves (70 mg) and N,N-dimethylformamide (5 mL) were used as the reaction solvent. The reaction was carried out at room temperature in an IKA2.0 electrochemical reactor with stainless steel as the cathode at a constant current of 1 mA for 24 hours. The conversion rate and yield were determined by hydrogen nuclear magnetic resonance spectroscopy with mesitylene as the internal standard. The ee value of the product was determined by chiral HPLC.

Example 49: Cross-coupling chiral nitrogen ligand screening

^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 sieves (70 mg) and N,N-dimethylacetamide (5 mL) were used as the reaction solvent. The reaction was carried out at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and stainless steel as the cathode at a constant current of 1 mA for 24 hours. The conversion rate and yield were determined by hydrogen nuclear magnetic resonance spectroscopy with mesitylene as the internal standard. The ee value of the product was determined by chiral HPLC.

Example 50: Optimization of reaction ^conditions using 1a and 6a

^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 sieves (70 mg) and N,N-dimethylacetamide (5 mL) were used as the reaction solvent. The reaction was carried out at room temperature in an IKA2.0 electrochemical reactor with iron as the anode and stainless steel as the cathode at a constant current of 1 mA for 24 hours. The conversion rate and yield were determined by hydrogen nuclear magnetic resonance spectroscopy with mesitylene as the internal standard. The ee value of the product was determined by chiral HPLC.

Example 51: Substrate synthesis

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

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 completed, the reaction mixture was stirred at room temperature for 2 h. After the stirring was completed, the reaction substrate S1 (1.0 equiv) was added to the reaction mixture and the temperature was raised to reflux for 2 h. After the reaction was completed, the reaction solution was cooled and quenched with a 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, and concentrated. The concentrate was purified by flash column chromatography to obtain the reaction intermediate S2.

S2 was dissolved in toluene (0.2 M), 2,3-dichloro-5,6-dicyano-p-benzoquinone (3.0 equiv) was added to toluene, the reaction solution was heated to reflux and samples were taken to monitor the progress of the reaction. After the reaction was completed, the reaction solution was cooled, filtered through diatomaceous earth, and the filtrate was concentrated by rotary evaporation. The concentrate was separated and purified by flash column chromatography to obtain intermediate S3.

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

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

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

Add 1-bromo-2-naphthoic acid (15.6mmol, 1.0equiv), N,N-dimethylformamide (25mL), N-iodosuccinimide (18.7mmol, 1.2equiv), palladium acetate (1.56mmol, 0.1equiv) to a dry 250mL round-bottom flask equipped with a stirrer. Heat the reaction solution to 100℃ and stir for 12h. After the reaction, cool the reaction solution to room temperature and dilute with ethyl acetate. Add saturated sodium carbonate solution to the solution, separate the liquids, extract the organic phase with saturated sodium carbonate, and combine the aqueous phases. Adjust the pH value of the aqueous phase to 1, a large amount of solids appear, add ethyl acetate to it, and the solids dissolve. Separate the mixed solution, extract the aqueous phase with ethyl acetate, combine the organic phases, dry over anhydrous magnesium sulfate, filter, and rotary evaporate to remove the solvent in the filtrate to obtain crude product S6, which is directly used in the next step.

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), DMF (25 mL) were added to a dry 250 mL round-bottom bottle equipped with a stirrer, and the reaction mixture was heated to 100 ° C and monitored by thin-layer chromatography. After the reaction was completed, the reaction mixture was filtered through celite, the filtrate was concentrated by rotary evaporation to remove the solvent, and the product S7 was separated and purified by flash column chromatography.

S7 (3 mmol, 1.0 equiv), potassium carbonate (2.0 equiv), tetrakistriphenylphosphine palladium (0.15 mmol, 0.05 equiv), arylboronic acid (3 mmol, 1.0 equiv), tetrahydrofuran (3 mL), water (3 mL) were added to a dry 50 mL sealed tube equipped with a stirrer, and then nitrogen was replaced three times. The reaction mixture was heated to 100 ° C and reacted for 12 h. After the reaction was completed, the reaction mixture was diluted with ethyl acetate, separated, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated by rotary evaporation. The concentrate was separated and purified by flash column chromatography to obtain the product S8.

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

S4 (1.0 equiv), potassium carbonate (2.0 equiv), and benzyl bromide (1.5 euqiv) were added to a 250 mL round-bottom flask equipped with a stirrer. The reaction mixture was heated to 70°C while stirring, and the reaction was monitored by thin-layer chromatography. After the reaction was completed, the reaction solution was cooled to room temperature, water and ethyl acetate were added to dilute the reaction solution, the liquid was separated, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, the organic phase was separated with saturated ammonium chloride aqueous phase. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated by rotary evaporation. The concentrate was separated by flash column chromatography to obtain the product S9.

(1a) was obtained by method III, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.43 (d, J = 8.4 Hz, 1H), 7.85-7.73 (m, 2H), 7.70-7.52 (m, 3H), 7.49 (d, J = 7.2 Hz, 2H), 7.43-7.30 (m, 3H), 5.44 (s, 2H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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(neat):2359,1732,1595,1495,1453,1381,1321,1263,1232,1171,1151,1121,978,952,866,819,783,762,734,694,662,614,581,532,471,443cm ^-1 .HRMS(ESI)theoretical value for C ₁₈ H ₁₃ O ₂ BrNa[M+Na] ⁺ :362.9991, experimental value:362.9990.

(1b) was obtained by method III, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.10 (s, 1H), 7.66-7.56 (m. 2H), 7.50 (d, J = 8.4 Hz, 1H), 7.39 (d, J = 7.2 Hz, 2H), 7.33-7.18 (m, 4H), 5.34 (s, 2H), 2.45 (s, 3H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )δ167.4,138.3,135.6,133.5,132.4,131.2,130.5,128.7,128.5,128.4,128.1,127.6,127.5,125.0,122.0,67.6,22.1.IR(neat):2960,2306,1720 ,1598,1548,1496,1452,1372,1299,1261,1230,1192,1147,1121,962,898,838,800,745,696,663,638,615,589,531,499,481,416cm ^-1 .HRMS (ESI) theoretical value for C ₁₉ H ₁₆ O ₂ Br [M+H] ⁺ : 355.0328, found value: 355.0324.

(1c) was obtained by method III, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.48 (d, J = 9.2 Hz, 1H), 7.98 (d, J = 8.8 Hz, 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 (101 MHz, CDCl ₃ ) δ 169.1, 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 for C ₁₉ H ₁₆ O ₂ Br[M+H] ⁺ :355.0334, Observation value:355.0325.

Obtained by method III (1d), ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05 (s, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.45 (d, J = 6.4 Hz, 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 (101 MHz, CDCl ₃ )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):3645,2338,1711,1601,1499,1458,1366,1314,1268,1188,1134,1070,1003,945,904,845,818,783,749,694,611,572,554,504,478cm ^-1 .HRMS(DART)theoretical value C ₂₀ H ₁₈ O ₂ Br[M+H] ⁺ :369.0485, Observational value:369.0480.

Obtained by method III (1e), ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.79–7.72 (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{ ¹ H}NMR (101 MHz, CDCl ₃ )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):3663,2974,1727,1 625,1597,1503,1453,1369,1298,1261,1219,1200,1121,1028,975,930,903,837,801,767,738,712,696,664,593,572,531,511,479,440,418cm ^-1 .HRMS (DART) theoretical value C ₁₉ H ₁₆ O ₃ Br [M+H] ⁺ : 371.0277, observed value: 371.0274.

Obtained by method III (1f), ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.28 (d, J = 9.2 Hz, 1H), 7.64-7.56 (m, 2H), 7.41 (d, J = 6.8 Hz, 2H), 7.37-7.25 (m, 3H), 7.21-7.16 (m, 1H), 7.01 (d, J = 2.4 Hz, 1H), 5.34 (s, 2H), 3.85 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ167.1,159.4,137.0,135.7,130.5,128.6,128.5,128.4(2C),127.8,126.8,126.5,123.2,120.8,105.9,67.5,55.5.IR(neat):3032,2338,1723,1 619,1559,1495,1476,1454,1402,1370,1319,1272,1229,1194,1170,1120,1029,981,852,820,790,772,742,696,677,602,533,497cm ^-1 .HRMS (DART) theoretical value C ₁₉ H ₁₆ O ₃ Br [M+H] ⁺ : 371.0277, observed value: 371.0274.

Obtained by method III (1 g) (1.29 g, 87%), ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.20 (d, J = 8.8 Hz, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.50-7.39 (m, 3H), 7.37-7.23 (m, 3H), 6.84 (d, J = 7.6 Hz, 1H), 5.36 (s, 2H), 3.92 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 for C ₁₉ H ₁₆ O ₃ Br[M+H] ⁺ :371.0277, Observed value:371.0274.

Obtained by method III (1h) (513 mg, 82%), ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.49 (d, J = 9.2 Hz, 1H), 7.99 (d, J = 1.6 Hz, 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{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₂ Br [M+H] ⁺ : 417.0485, observed value: 417.0480.

Obtained by method III (1i) (478 mg, 75%), ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (d, J = 9.6 Hz, 1H), 7.66 (dd, J = 21.2, 8.4 Hz, 2H) ,7.48(d,J＝6.8Hz,2H),7.42–7.30(m,3H),7.25(dd,J＝9.2,2.4Hz,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{ ¹ H}NMR (101MHz, CDCl ₃ )δ167.1,158.8,137.6,137.0,135.7,130.4,128.6,128.5,128.4,128.2,127.7,126.8,126.4,123.3,121.1,115.5,106.6,67.5, 67.4,30.1,28.3 .IR(neat):3060,2939 ,2853,1726,1619,1495,1464,1426,1394,1369,1345,1326,1261,1233,1177,1121,1080,1050,1019,961,903,852,820,797,746,728,695,643,604,546,514,485,413cm ^-1 .HRMS (DART) theoretical value C ₂₃ H ₂₂ O ₃ I[M+H] ⁺ :425.0747, Exp. value:425.0743.

(2a) (1.2 g, 37%) was obtained by method I. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.49 (d, J=8.4 Hz, 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 (101 MHz, CDCl ₃ ) δ 165.9, 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.

(2b) (683 mg, 52.2%) was obtained by method I, ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.42 (d, J = 8.8 Hz, 1H), 7.86 (dd, J = 20.4, 8.4 Hz, 2H), 7.66 (s, 1H), 7.59-7.42 (m, 3H), 7.38-7.27 (m, 3H), 2.87 (q, J = 7.6 Hz, 2H), 1.36 (t, J = 7.6 Hz, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 for C ₁₉ H ₁₆ O ₂ Br[M+H] ⁺ :355.0328,observation value:355.0326.

(2c) (1.6 g, 80%) was obtained by method I. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.57 (d, J = 8.8 Hz, 1H), 8.08 (s, 1H), 7.99-7.90 (m, 3H), 7.76 (d, J = 8.0 Hz, 2H), 7.58-7.40 (m, 5H), 7.38-7.28 (m, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₂ Br[M+H] ⁺ :403.0328,Experimental value:403.0327.

(2d) (1.03 g, 72%) was obtained by method I. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.41 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.4 Hz, 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 (101 MHz, CDCl ₃ )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 O ₃ Br[M+H] ⁺ :357.0121, experimental value:357.0120.

6-Hydroxy-4-hydronaphthalenone (30 mmol, 1.0 equiv), potassium carbonate (60 mmol, 2.0 equiv), 5-bromo-1-pentene (45 mmol, 1.5 euqiv), and DMF (50 mL) were added to a 250 mL round-bottom flask equipped with a stirrer. The reaction mixture was heated to 60°C and monitored by thin-layer chromatography. After the reaction, the reaction solution was cooled, diluted with ethyl acetate and water, separated, the organic phase was washed with saturated ammonium chloride, separated, the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated by rotary evaporation to obtain a crude product S10. The crude product S10 was used as a raw material to obtain 2e by method 1. ¹ H NMR (400MHz, CDCl ₃ )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,CDCl ₃ )δ165.7,159.1,150.9,137.6,137.3,130.6,129.5,127.6,127.5,126.9,126.6,126.1,124.0,121.7,121.24115.5,106.7,67.5,30.1,28.3.IR(ne at):3072,1741,1616,1591,1490,1461,1370,1313,1267,1221,1191,1102,1011,946,909,853,823,752,734,690,572,513,499,415cm ^-1 .HRMS (DART) theoretical value C ₂₂ H ₂₀ O ₃ Br [M+H] ⁺ : 411.0590, found value: 411.0588.

(2f) (1.2 g, 83%) was obtained by method I. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.25 (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 (101 MHz, CDCl ₃ )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 for C ₁₈ H ₁₄ O ₂ Br[M+H]:341.0172, Found:341.0170.

Obtained by method I (2g) (1.8g, 70%), ^1H NMR (400MHz, CDCl ₃ ) δ8.12 (d, J=11.2Hz, 1H), 7.92-7.77 (m, 3H), 7.55-7.26 (m, 6H). ^13C { ¹ H} NMR (101MHz, CDCl ₃ ) 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 (376 MHz, CDCl ₃ ) 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, 427 cm ^-1 . HRMS (ESI) theoretical value for C ₁₇ H ₁₀ O ₂ BrFNa[M+Na] ⁺ : 366.9740, found value: 366.9740.

Obtained by method I (2h) (412 mg, 80%), ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.39 (d, J = 8.4 Hz, 1H), 8.11 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 8.8 Hz, 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 = 6.8 Hz, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 ,2852,1743,1591,1489,1458,1359,1327,1270,1253,1191,1159,1115,1090,1023,939,909,839,822,805,791,753,733,686,638,584,558,527,508,480,425cm ^{- 1} .HRMS (ESI) theoretical value C ₂₂ H ₂₂ O ₂ Br[M+H] ⁺ :397.0789, experimental value:397.0787.

Obtained by method I (532 mg, 35%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.36 (d, J = 8.8 Hz, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.60-7.52 (m, 1H), 7.50-7.40 (m, 2H), 7.36-7.26 (m, 3H), 6.95 (d, J = 7.6 Hz, 1H), 4.02 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 O ₃ Br[M+H] ⁺ :357.0121, experimental value:357.0120.

Obtained by method I (1.72 g, 68%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.49 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.4 Hz, 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 (101 MHz, CDCl ₃ )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 for C ₁₈ H ₁₄ O ₂ Br[M+H] ⁺ :341.0172, Observed value:341.0172.

2k (840 mg, 69%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.38 (d, J = 8.4 Hz, 1H), 7.91-7.83 (m, 2H), 7.71-7.41 (m, 7H), 7.37-7.14 (m, 3H), 6.81 (d, J = 8.0 Hz, 2H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ166.4,150.4,139.5,137.8,134.2,133.8,130.8,129.5,129.1,128.8,128.6,128.5,128.3(2C),128.2,127.7,126.2,121.4,120.7.IR(neat):305 4,1744,1589,1484,1325,1251,1218,1188,1159,1096,1024,978,923,900,846,770,742,720,701,687,647,608,581,546,504,481cm ^-1 .HRMS (ESI) theoretical value C ₂₃ H ₁₉ O ₂ NBr [M + NH ₄ ] ⁺ : 420.0594, found value: 420.0594.

Obtained 2l (834 mg, 65%) by method II. ¹ H NMR (400MHz, CDCl ₃ ) δ 8.37 (d, J = 8.0 Hz, 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, CDCl ₃ )δ166.5,150.4,144.5,137.9,136.8,134.2,134.0,130.7,129.4,129.1,128.6,128.4,128.2,128.1,127.7,126.2,121.5,120.6,28.7,15.9.IR(neat):3065,1745, 1589,1483,1442,1255,1217,1185,1158,1136,1116,1093,1020,980,924,896,844,745,689,620,583,496 cm ^-1 .HRMS (ESI) theoretical value C ₂₅ H ₁₉ O ₂ BrNa[M+Na] ⁺ :453.0461, experimental value:453.0462.

Obtained 2m (792mg, 59%) by method I. ¹ H NMR (400MHz, CDCl ₃ ) δ 8.39 (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, CDCl ₃ )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):2952,2864,1753,1590,1484,1326,1253,1216,1184,1159,1134,1091,1022,980,923,896,824,771,743,690,610,581,540,500,460cm ^-1 .HRMS(ESI)theoretical value C ₂₆ H ₂₂ O ₂ Br[M+H] ⁺ :445.0798, Observational value:445.0796.

Obtained 2n (757mg, 57%) by method II. ¹ H NMR (400MHz, CDCl ₃ ) 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{ ¹ H}NMR (101MHz, CDCl ₃ )δ166.5,150.4,149.0,137.9,137.0,134.2,134.0,130.7,129.4,129.1,128.6,128.4,128.2,128.2,127.7,126.7,126.2,121.5,120.5,34.0,2 4.1. 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 O ₂ Br[M+ H] ⁺ :445.0798, experimental value:445.0798.

2o (1.12 g, 82%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.38 (d, J = 8.4 Hz, 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 = 8.0 Hz, 2H), 1.40 (s, 9H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 for C ₂₇ H ₂₄ O ₂ Br[M+H] ⁺ :459.0954, Observed value:459.0956.

2p (879 mg, 68%) was obtained by method II (The yield of the last step). ¹ H NMR (400MHz, CDCl ₃ ) δ 8.37 (d, J = 8.4 Hz, 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, CDCl ₃ )δ166.6,159.7,150.4,137.5,134.2,134.0,131.8,130.6,130.3,129.5,128.7,128.4,128.2,128.1,127.6,126.2,121.5,120.6,114.1,55.5.IR(neat):3057,1742, 1591,1514,1485,1459,1290,1257,1224,1177,1159,1088,1025,923,891,848,826,743,687,619,541,517,497cm ^-1 .HRMS (ESI) theoretical value C ₂₄ H ₁₇ O ₃ BrNa[M+Na] ⁺ :455.0253, experimental value:455.0255.

2q (723 mg, 51%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.40 (d, J = 8.4 Hz, 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 = 8.4 Hz, 2H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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, 475 cm -1 . HRMS (DART) theoretical value for C ₂₉ H ₂₀ O ₂ Br [M+H] ⁺ : 479.0641, found value: 479.0642.

2r (957 mg, 76%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.38 (d, J = 8.4 Hz, 1H), 7.93-7.81 (m, 2H), 7.76-7.50 (m, 4H), 7.42-7.12 (m, 5H), 6.87 (d, J = 7.6 Hz, 2H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ166.3,162.9(d,J＝248.5Hz),150.3,136.6,135.4(d,J＝4.0Hz),134.1,133.8,130.9,130.8,129.6,128.8,128.4(2C),127.7,126.3,121.3,120. 8,115.6 (d, J=21.2Hz). ¹⁹ F NMR (376MHz, CDCl ₃ )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 for C ₂₃ H ₁₅ O ₂ BrF[M+H] ⁺ :421.0234, Observed value:421.0227.

2s (851 mg, 65%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.37 (d, J = 8.4 Hz, 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 = 7.6 Hz, 2H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ166.2,150.3,137.9,136.4,134.5,134.1,133.5,130.9,130.4,129.6,128.8,128.8,128.5,128.5,128.4,127.7,126.4,121.3,120.9.IR(neat):1746,1591,1488,1441,1259,1222,1188,1159,1132,1079,1013,976,920,900,846,818,771,731,688,610,578,542,515,481,446cm ^-1 .HRMS(DART)theoretical valueC ₂₃ H ₁₅ O ₂ BrCl[M+H] ⁺ :436.9938, Observational value:436.9939.

2t (742 mg, 56%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.40 (d, J = 8.4 Hz, 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{ ¹ H} NMR (101 MHz, CDCl ₃ )δ197.6,166.1,150.3,144.1,136.6,136.5,134.0,133.3,131.1,129.6,129.3,128.9,128.7,128.6(2C),128.5,127.7,126.4,121.2(2C),26.8 .IR(neat ):2987,1745,1683,1590,1484,1435,1403,1356,1256,1222,1182,1158,1092,1070,1015,957,920,892,852,825,735,685,599,579,541,516,500,483cm ^-1 .HRMS (ESI) theoretical value for C ₂₅ H ₁₈ O ₃ Br [M+H] ⁺ :445.0439, found value:445.0430.

2u (952 mg, 73%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.40 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.4 Hz, 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 (101 MHz, CDCl ₃ )δ166.8,166.1,150.3,144.0,136.6,134.1,133.3,131.0,129.9,129.6,129.1,128.9,128.7,128.6,128.5,127.7,126.3,121.2,121.1,52.3.IR(neat):3059,2916,2853,1739,1591,1487,1431,1374,1263,1224,1188,1159,1105,1021,974,921,896,828,742,688,503cm ^-1 .HRMS(ESI)theoretical value for C ₂₅ H ₁₈ O ₄ Br[M+H] ⁺ :461.0383, Observational value:461.0384.

2v (812 mg, 58%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.39 (d, J = 8.4 Hz, 1H), 7.94-7.83 (m, 2H), 7.81-7.61 (m, 6H), 7.33 (t, J = 7.8 Hz, 2H), 7.28-7.18 (m, 1H), 6.79 (d, J = 8.4 Hz, 2H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )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, CDCl ₃ )δ-62.56. IR(neat):3066,1740,1590,1484,1444,1321,1252,1219,1182,1161,1124,1098,1065,1017,984,926,897,851,828,768,746,720,689,613,587,518cm ^-1 . HRMS(DART)theoretical value for C ₂₄ H ₁₅ O ₂ BrF ₃ [M+H] ⁺ :471.0202, Observed value:471.0199.

2w (723 mg, 51%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.41 (d, J = 8.4 Hz, 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 = 8.4 Hz, 2H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )δ166.5,150.4,141.6,140.6,139.9,137.7,134.2,133.8,130.9,129.5,129.1,128.9,128.8,128.5,128.4,128.3,128.0,127.9,127.7,127.6, 127.3,126. 9,126.2,121.4,120.8. IR(neat):3052,1744,1590,1484,1260,1219,1182,1157,1130,1096,984,901,855,835,765,737,703,685,579,560,520,495,468cm ^-1 . HRMS(DART)theoretical value for C ₂₉ H ₂₀ O ₂ Br[M+H] ⁺ :479.0641, Observation value:479.0645.

2x (852 mg, 66%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.37 (d, J = 8.4 Hz, 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 = 7.6 Hz, 2H), 3.82 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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),127.7,126.2,121.5,121.5,120.8,114.5,11 4.1,55.4.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 for C ₂₄ H ₁₈ O ₃ Br [M+H] ⁺ :433.0434, found value:433.0433.

Obtained 2y (945mg, 72%) by method II. ¹ H NMR (400MHz, CDCl ₃ ) δ 8.39 (d, J = 8.0Hz, 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, CDCl ₃ )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),134.0,133.1,131.2 ,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, CDCl ₃ )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 O ₂ BrF ₂ [M+H] ⁺ :439.0140, Observation:439.0139.

2z (948 mg, 70%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.40 (d, J=8.4 Hz, 1H), 8.06 (s, 1H), 7.98-7.85 (m, 5H), 7.74-7.60 (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 (101 MHz, CDCl ₃ )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. 7,12 6.6, 126.2, 121.4, 120.9. IR (neat): 3050, 2389, 1744, 1588, 1483, 1444, 1254 ^, 1215, 1182, 1157, 1088, 991, 927, 908, 890, 820, 743, 692, 582, 516, 477 cm -1 . HRMS (DART) theoretical value for C ₂₇ H ₁₈ O ₂ Br [M+H] ⁺ : 453.0485, found value: 453.0476.

2ab (892 mg, 73%) was obtained by method II. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.31 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 7.6 Hz, 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{ ¹ H} NMR (101 MHz, CDCl ₃ )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(n eat):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 for C ₂₃ H ₂₀ O ₂ Br [M+H] ⁺ :407.9641, found value:407.0641.

2ab (1.42 g, 73%) was obtained by Method I. ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.03 (d, J = 4.0 Hz, 1H), 8.82 (d, J = 8.4 Hz, 1H), 8.18 (q, J = 8.8 Hz, 2H), 7.64-7.58 (m, 1H), 7.52-7.41 (m, 2H), 7.37-7.28 (m, 3H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )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):2987,1747,1586,1552,1484,1452,1409,1325,1258,1223,1177,1163,1112,1036,1018,968,927,900,845,810,793,752,691,667,616,569,537,511,488,461cm ^{-1 .} HRMS(DART)theoretical value for C ₂₃ H ₂₀ O ₂ Br[M+H] ⁺ :327.9968, experimental value:327.9964

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) to a 250 mL round-bottom flask equipped with a stirrer. The reaction mixture was stirred at room temperature for 4 h. After the reaction was completed, the reaction was quenched with a saturated sodium bisulfite solution, the liquid was separated, and the aqueous phase was extracted with dichloromethane. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated to remove the solvent to obtain the crude product 1-iodo-2-naphthol. Add crude 1-iodo-2-naphthol, potassium carbonate (100 mmol, 2.0 equiv), benzyl bromide (62.5 mmol, 1.25 equiv), and DMF (100 mL) to a dry 250 mL round-bottom flask equipped with a stirrer. The reaction mixture was heated to 70°C for reaction and monitored by thin plate chromatography. After the reaction, the reaction mixture was diluted with water and ethyl acetate, separated, the organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated to remove the solvent. The concentrate was separated and purified by flash column chromatography to obtain substrate 6a (15.2 g, 84%). ¹ H NMR (400 MHz, CDCl ₃ ) δ8.17 (d, J＝8.4 Hz, 1H), 7.85–7.67 (m, 2H), 7.65–7.50 (m, 3H), 7.46–7.31 (m, 4H), 7.20 (d, J＝8.8 Hz, 1H), 5.30 (s, 2H).

6-cyclopropyl-1-bromo-2-benzyloxynaphthalene (3.9 mmol, 1.0 equiv) and THF (20 mL) were added to a 100 mL three-necked flask equipped with a stirrer. After nitrogen was purged, the mixture was stirred at -78 °C at low temperature, and then n-butyl lithium (4.7 mmol, 1.2 equiv) was added. The reaction mixture was stirred at -78 °C for 1 h, and then iodine (7.8 mmol, 2.0 equiv) was added thereto. The reaction mixture was reacted at room temperature for 3 h. After the reaction was completed, a saturated sodium thiosulfate solution was added to quench the reaction, and the liquid 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 flash column chromatography to obtain product 6b (921 mg, 59%). ¹ H NMR (400 MHz, CDCl ₃ ) δ8.03 (d, J = 8.8 Hz, 1H), 7.64 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 7.2 Hz, 2H), 7.45–7.27 (m, 4H), 7.26–7.20 (m, 1H), 7.13 (d, J = 8.8 Hz, 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 (101 MHz, CDCl ₃ )δ155.2,140.2,136.8,134.1,131.4,130.2,129.5,128.6,128.0,127.3,126.9,124.1,115.0,89.0,72.0,15.2,9.2.IR(neat):3029,2106,1808,15 ^-1 .HRMS (DART) theoretical value C ₂₀ H ₁₇ OI [M+H] ⁺ : 400.0319, found value: 400.0316.

6-cyclohexyl-1-bromo-2-benzyloxynaphthalene (4.0 mmol, 1.0 equiv) and THF (20 mL) were added to a 100 mL three-necked flask equipped with a stirrer. After nitrogen was purged, the mixture was stirred at -78 °C at low temperature, and then n-butyl lithium (4.8 mmol, 1.2 equiv) was added. The reaction mixture was stirred at -78 °C for 1 h, and then iodine (8.0 mmol, 2.0 equiv) was added thereto. The reaction mixture was reacted at room temperature for 3 h. After the reaction was completed, a saturated sodium thiosulfate solution was added to quench the reaction, the liquid 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 flash column chromatography to obtain product 6c (922 mg, 52%). ¹ H NMR (400 MHz, CDCl ₃ ) δ8.07 (d, J = 8.8 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.56–7.47 (m, 3H), 7.45–7.27 (m, 4H), 7.15 (d, J = 9.2 Hz, 1H), 5.27 (s, 2H), 2.64 (t, J = 11.2 Hz, 1H), 2.05–1.68 (m, 5H), 1.62–1.21 (m, 5H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )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):3668,3 023,2927,2851,2319,2123 ,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 for C ₂₃ H ₂₃ OI [M+H] ⁺ : 443.0872, observed value: 443.0863.

A dry 500 mL round-bottom flask equipped with a stirrer was added with a stirrer, and 6-formyl-2-benzyloxynaphthalene (76 mmol, 1.0 equiv), DMF (100 mL), MeCN (100 mL), and p-toluenesulfonic acid (76 mmol, 1.0 equiv) were added. N-iodosuccinimide (83.7 mmol, 1.1 equiv) was added to the reaction at 0°C, and the reaction was allowed to react overnight at room temperature after the addition was completed. After the reaction was completed, the reaction solution was quenched with a saturated sodium thiosulfate solution, and the reaction solution was diluted with dichloromethane, separated, and the organic phase was washed with a saturated ammonium chloride solution. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated by rotary evaporation to obtain S11 (13.5 g, 34%).

S11 (15 mmol, 1.0 equiv) and ethanol (100 mL) were added to a dry round-bottomed bottle equipped with a stirrer and stirred in an ice bath. Sodium borohydride (30 mmol, 2.4 equiv) was added to the reaction mixture at 0°C. After the addition was completed, the mixture was left to react overnight at room temperature. After the reaction was completed, the reaction was quenched with saturated ammonium chloride solution, and the ethanol was removed by rotary evaporation. The mixture after the ethanol was removed 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 to remove the solvent to obtain the crude product S12.

In a dry 250 mL round-bottom bottle equipped with a stirrer, S12, dichloromethane (100 mL), pyridine (30 mmol, 2.0 equiv) were added, and acetic anhydride (22.5 mmol, 1.5 equiv) was added thereto at 0° C. The reaction mixture was stirred at room temperature overnight. After the reaction, the solvent in the mixture was removed by rotary evaporation, and the concentrate was separated and purified by flash column chromatography to obtain product 6d (3.9 g, 60%). White solid, mp = 79.5-80.7 °C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.17 (d, J = 8.4 Hz, 1H), 7.82-7.67 (m, 2H), 7.61-7.47 (m, 3H), 7.46-7.30 (m, 3H), 7.22 (d, J = 8.8 Hz, 1H), 5.31 (s, 2H), 5.26 (s, 2H), 2.13 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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):2960,1729 ,1 630,1593,1494,1458,1377,1330,1259,1216,1167,1081,1035,959,928,892,867,843,814,799,779,753,720,699,645,611,541,517,493,468,441 cm ^-1 . HRMS (DART) theoretical value for C ₂₀ H ₁₇ O ₃ I [M+H] ⁺ : 432.0217, found value: 432.0212.

Methyltriphenylphosphonium bromide (20 mmol, 2.0 equiv) and tetrahydrofuran (100 mL) were added to a dry 250 mL round-bottom flask equipped with a stirrer. Potassium tert-butoxide (15 mmol, 1.5 equiv) was added thereto under stirring at 0°C, and stirring was continued for 15 min. After 15 min, S11 (10 mmol, 1.0 equiv) was added thereto. After the addition of the materials, the reaction mixture was reacted at room temperature for 4 h. After the reaction was completed, the reaction was quenched with water, the liquid was separated, the aqueous phase was extracted with ethyl acetate (3×50 mL), the organic phases were combined, the organic phases were dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated to remove the solvent, and the concentrate was separated by flash column chromatography to obtain product 6e (1.73 g, 45%). White solid, mp = 118.4-119.7 °C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.08 (d, J = 8.8 Hz, 1H), 7.74-7.47 (m, 5H), 7.43-7.28 (m, 3H), 7.12 (d, J = 8.8 Hz, 1H), 6.83 (dd, J = 17.6, 10.8 Hz, 1H), 5.83 (d, J = 17.6 Hz, 1H), 5.31 (d, J = 10.8 Hz, 1H), 5.24 (s, 2H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )δ155.9,136.6,136.3,135.5,133.8,131.6,130.4,130.1,128.6,128.0,127.2,126.5,125.5,114.9,114.3,88.9,71.9.IR(neat):3660,2985,2319 ,1816,1587,1493,1448,1384,1334,1264,1227,1171,1133,1078,1051,983,904,884,819,791,760,734,692,642,532,505,467,413cm ^-1 .HRMS (DART) theoretical value C ₁₉ H ₁₆ OI [M+H] ⁺ : 387.0240, observed value: 387.0237.

6-methoxy-1-bromo-2-benzyloxynaphthalene (5mmol, 1.0equiv) and THF (20mL) were added to a 100mL three-necked flask equipped with a stirrer. After nitrogen was purged, the mixture was stirred at -78°C, and then n-butyl lithium (6mmol, 1.2equiv) was added. The reaction mixture was stirred at -78°C for 1h, and then iodine (10mmol, 2.0equiv) was added thereto. The reaction mixture was reacted at room temperature for 3h. After the reaction was completed, a saturated sodium thiosulfate solution was added to quench the reaction, the liquid was separated, and the aqueous phase was extracted with ethyl acetate (3×100mL). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated by rotary evaporation. The concentrate was purified by flash column chromatography to obtain product 6f (903 mg, 47%). Yellow solid, mp = 123.6-125.5 °C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.07 (d, J = 9.2 Hz, 1H), 7.64 (d, J = 8.9 Hz, 1H), 7.55 (d, J = 7.5 Hz, 2H), 7.44-7.28 (m, 3H), 7.26-7.10 (m, 3H), 7.04 (d, J = 2.2 Hz, 1H), 5.24 (s, 2H), 3.90 (s, 3H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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):3654,2319,1812,1626,1595,1496,1452,1370,1344,1248,1228,1195,1167,1124,1080,1059,1025,970,937,877,845,813,792,732,693,646,575,548,506,464,415cm ^-1 .HRMS (DART) theoretical value for C ₁₈ H ₁₆ O ₂ I [M+H] ⁺ : 391.0189, observed value: 391.0185.

To a dry 500 mL single-mouth bottle equipped with a stirrer, add 6-oxybenzyl-2-naphthocarbonitrile (20 mmol, 1.0 equiv), DMF (50 mL), acetonitrile (50 mL), p-toluenesulfonic acid (20 mmol, 1.0 equiv). Add N-iodosuccinimide (22 mmol, 1.1 equiv) at 0°C. After the addition, the reaction mixture was reacted at room temperature overnight. After the reaction was completed, the reaction was quenched with a saturated sodium thiosulfate solution, the reaction solution was diluted with dichloromethane, the liquid was separated, and the organic phase was washed with saturated ammonium chloride water. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated by rotary evaporation to obtain the crude product S11.

Add crude product S11, sodium hydroxide (80mmol, 4.0equiv), water (50mL), methanol (50mL), and tetrahydrofuran (50mL) to a dry 250mL round-bottom flask equipped with a stirrer. Heat the reaction mixture to reflux for 48h. After stopping the reaction, cool the reaction 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 the organic phases with anhydrous magnesium sulfate, and remove the solvent from the filtrate by rotary evaporation to obtain crude product S12 for the next step.

Add crude product S11, potassium carbonate (40 mmol, 2.0 equiv), DMF (50 mL), and iodomethane (30 mmol, 1.5 equiv) to a dry 250 mL round-bottom flask equipped with a stirrer. Heat the mixture to 50 °C and react for 3 h. After the reaction, add ethyl acetate (500 mL) and water (200 mL) to the mixture, separate the liquids, and use ethyl acetate (3×100 mL) for the aqueous phase. The organic phases were combined, washed with saturated ammonium chloride, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated by rotary evaporation. The concentrate was separated and purified by flash column chromatography to obtain 6 g (3.72 g, 44%) of the product. ¹ H NMR (400 MHz, CDCl ₃ ) δ8.47 (s, 1H), 8.18 (d, J = 9.2 Hz, 1H), 8.08 (d, J = 9.2 Hz, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 7.6 Hz, 2H), 7.45–7.30 (m, 3H), 7.24 (d, J = 8.8 Hz, 1H), 5.33 (s, 2H), 3.97 (s, 3H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )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):2943,1693,1620, ^{1594,1495,1472,1428,1397,1343,1327,1284,1266,1237,1197,1135,1104,1043,981,912,865,844,794,766,733,696,630,552,497,415cm -1} .HRMS (DART) theoretical value for C ₁₉ H ₁₆ O ₃ I [M+H] ⁺ : 419.0139, found value: 419.0134.

Example 52 General Procedure for Ligand Synthesis

A stirring bar was added to a 250 mL single-mouth bottle, and 5-2af (50 mmol, 1.0 equiv.) and dichloromethane (200 mL) were added. Meta-chloroperbenzoic acid (60 mmol, 1.2 equiv.) was added at 0°C, and the mixture was allowed to react at room temperature for 12 hours. After the reaction was completed, the reaction was quenched with a saturated sodium sulfite solution, and a saturated potassium carbonate solution was added to make the reaction alkaline. The liquids were 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 a crude product 5-2ag.

A stirring bar was added to a 500 mL single-mouth bottle, and crude 5-2ag, dichloromethane (200 mL), trimethylsilyl cyanide (62.5 mmol, 1.25 equiv.), and dimethylcarbamoyl chloride (62.5 mmol, 1.25 equiv) were added. The reaction was allowed to react at room temperature for 24 hours after the addition was completed. After the reaction was completed, the reaction was quenched with a saturated potassium carbonate solution (slowly added). The liquid was separated, the aqueous phase was extracted three times with dichloromethane, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, the solvent was removed by rotary evaporation, and the product 5-2ah was purified by flash column chromatography.

A stirring bar was added to a 250 mL single-mouth bottle, and 5-2ah (20 mmol, 1.0 equiv.), methanol (50 mL), and sodium methoxide (4 mmol, 20 mol%) were added. The reaction was stirred at room temperature and monitored by TLC. After the reaction was completed, methanol was removed by rotary evaporation, ethyl acetate was added to dissolve the product, and sodium methoxide was removed by filtration on a sand core funnel pad with silica gel. The filtrate was evaporated to remove the solvent to obtain a crude product of 5-2ai for use.

A stirring bar was added to a 100 mL single-mouth bottle, and 5-2ai crude product, p-toluenesulfonic acid (4mmol, 20mol%), toluene (50mL), and the corresponding amino alcohol (30mmol, 1.5euqiv.) were added. After the addition of the materials, the reaction was refluxed and monitored by TLC until the substrate was completely reacted. After the reaction was completed, the reaction solution was restored to room temperature and the reaction solution was directly purified by flash column chromatography to obtain the product pyridine oxazoline ligand.

Ligand L8 was synthesized from 2-butylpyridine and (1S,2R)-aminoindanol by a general procedure. White solid, 4.6 g, the yield of the last two steps is 44%, ¹ H NMR (400 MHz, CDCl ₃ ) δ7.84 (d, J=7.6 Hz, 1H), 7.66-7.55 (m, 2H), 7.29-7.23 (m, 3H), 7.20 (d, J=8.0 Hz, 1H), 5.78 (d, J=8.0 Hz, 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=8.0 Hz, 3H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )δ163.5,162.9,146.4,141.7,139.9,136.6,128.5,127.4,125.8,125.3,124.5,121.6,83.9,77.0,39.9,38.3,32.3,22.6,14.0.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 N ₂ O[M+H] ⁺ :293.1648, experimental value:293.1654.[α] ^29.8 ＝-192.86(c＝1.0,CHCl ₃ ).

Ligand L9 was synthesized from 2-pentylpyridine and (1S,2R)-aminoindanol by a general procedure. White solid, 2.5 g, the yield of the last two steps is 40%, ¹ H NMR (400 MHz, CDCl ₃ ) δ7.85 (d, J=7.6 Hz, 1H), 7.65–7.55 (m, 2H), 7.30–7.23 (m, 3H), 7.21 (d, J=7.6 Hz, 1H), 5.78 (d, J=8.0 Hz, 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=8.0 Hz, 3H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )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):2949,2926,2854,1627,1573,1460,1364,1291,1233,1160,1121,1088,1065,1022,996,856,810,744,672,648,623,454cm ^-1 .HRMS(ESI)theoretical value C ₂₀ H ₂₃ N ₂ O[M+H] ⁺ :307.1805, Observed value:307.1808.[α] ^28.8 ＝-197.69 (c＝1.0, CHCl ₃ ).

Ligand L17 was synthesized from 2-hexylpyridine and (1S,2R)-aminoindanol by a general procedure. White solid, 7.4 g, the yield of the last two steps is 38%, ¹ H NMR (400 MHz, CDCl ₃ ) δ7.84 (d, J=7.8 Hz, 1H), 7.67–7.54 (m, 2H), 7.32–7.16 (m, 4H), 5.78 (d, J=8.0 Hz, 1H), 5.62–5.52 (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=5.2 Hz, 3H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )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(ne at):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 for C ₂₁ H ₂₅ N ₂ O [M+H] ⁺ : 321.1961, found value: 321.1964. [α] ^26.5 = -192.88 (c = 1.0, CHCl ₃ ).

Ligand L14 was synthesized from 2-isopropylpyridine and (1S,2R)-aminoindanol by a general procedure. 4.8 g, 51% yield in the last two steps, ¹ H NMR (400 MHz, CDCl ₃ ) δ7.84 (d, J=7.6 Hz, 1H), 7.71–7.55 (m, 2H), 7.34–7.16 (m, 4H), 5.78 (d, J=8.0 Hz, 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, 1.2 Hz, 6H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )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 N ₂ O[M+H] ⁺ :279.1492, experimental value:279.1501.[α] ²⁹ .7＝-223.34(c＝1.0,CHCl ₃ ).

Ligand L15 was synthesized from 2-phenylpyridine and (1S,2R)-aminoindanol by a general procedure. Colorless crystals were obtained after recrystallization, 5.1 g, and the yield of the last two steps was 65%. White solid, mp = 117.9-119.6 °C. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.06-7.91 (m, 3H), 7.84-7.72 (m, 2H), 7.65-7.55 (m, 1H), 7.51-7.35 (m, 3H), 7.32-7.22 (m, 3H), 5.82 (d, J = 8.0 Hz, 1H), 5.66-5.52 (m, 1H), 3.61-3.39 (m, 2H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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 ₁₇ N ₂ O[M+H] ⁺ :313.1335, Found:313.1341.[α] ^24.7 ＝-269.91(c＝1.0,CHCl ₃ ).

Ligand L16 was synthesized from 2-benzylpyridine and (1S,2R)-aminoindanol by a general procedure. White solid, 3.9 g, 67% yield in the last two steps, ¹ H NMR (400 MHz, CDCl ₃ ) δ7.86 (d, J=7.6 Hz, 1H), 7.70–7.50 (m, 2H), 7.41–7.15 (m, 8H), 7.06 (d, J=8.0 Hz, 1H), 5.80 (d, J=8.0 Hz, 1H), 5.65–5.44 (m, 1H), 4.26 (s, 2H), 3.61–3.41 (m, 2H). ¹³ C{ ¹ H}NMR (101 MHz, CDCl ₃ )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 ): 2929,1649,1628,1567,1492,1452,1364,1296,1214,1165,1120,1103,1080,1025,994,941,853,797,743,717,694,671,630,594,569,521,482,450 cm ^-1 . HRMS (ESI) theoretical value for C ₂₂ H ₁₉ N ₂ O [M+H] ⁺ : 327.1492, found value: 327.1493. [α] ^29.6 = -148.56 (c = 1.0, CHCl ₃ ).

Ligand L19 was synthesized from 2-(1-ethylpropyl)pyridine and (1S,2R)-aminoindanol by a general procedure. Yellow oil, 3.5 g, 40% yield in the last two steps. ¹ H NMR (400MHz, CDCl ₃ ) 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, CDCl ₃ )δ165.9,163.7,146.4,141.8,140.0,136.3,128.5,127.4,125.8,125.3,123.5,121.9,83.8,77.0,51.1,39.9,28.0,27.9,11.9(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 N ₂ O[M+H] ⁺ :307.1805, experimental value:3071809.[α] ^23.9 ＝-183.60(c＝1.0,CHCl ₃ ).

Ligand L20 was synthesized from 2-isobutylpyridine and (1S,2R)-aminoindanol by a general procedure. White solid, the yield of the last two steps was 54%, ¹ H NMR (400 MHz, CDCl ₃ ) δ7.85 (d, J = 7.6 Hz, 1H), 7.66-7.54 (m, 2H), 7.32-7.22 (m, 3H), 7.17 (d, J = 8.0 Hz, 1H), 5.79 (d, J = 8.0 Hz, 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 = 6.4 Hz, 6H). ¹³ C{ ¹ H} NMR (101 MHz, CDCl ₃ )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(neat):3347,29 ^{57,1655,1588,1518,1448,1412,1335,1258,1176,1150,1083,1056,994,878,843,816,767,739,706,664,632,613,582,531,507,466,423cm -1} .HRMS (ESI) theoretical value for C ₁₉ H ₂₁ N ₂ O [M+H] ⁺ : 293.1648, found value: 293.1641. [α] ^26.6 = -214.93 (c = 1.0, CHCl ₃ ).

Example 53 Preparation of Complex 9

Add a stirrer to a 20mL sealed tube, add L5 (1mmol, 2.0equiv.), cobalt iodide (0.5mmol, 1.0equiv.), acetonitrile (5mL), and stir the reaction at room temperature for 30 minutes after the addition is completed. After the reaction is completed, filter the reaction solution with a sand core funnel, collect the filtrate, add ether (20mL) to the filtrate, and a large amount of green solid precipitates. Filter the solid with a funnel, recrystallize with methanol and ethyl acetate to obtain dark green crystals suitable for X-ray single crystal diffraction, 250mg, and the yield is 62%.

Crystal parameters of complex 9

Claims (13)

1. A method for asymmetric coupling, characterized in that it comprises the following steps: in a solvent, in the presence of a Co salt, a chiral nitrogen ligand and an electrolyte, subjecting a compound as shown in formula I to an electrochemical asymmetric coupling reaction as shown below with a compound as shown in formula II to obtain a compound as shown in formula III or a compound as shown in formula IV; in: Ring A and Ring A' are independently _C6 - _C10 aryl, _C6 - _{C10 aryl} ^substituted by one or more Ra, 5-10 membered heteroaryl or 5-10 membered heteroaryl substituted by one or more ^Rb ; when there are multiple substituents, they are the same or different; in the 5-10 membered heteroaryl or the 5-10 membered heteroaryl substituted by one or more ^Rb , the heteroatom is selected from N, O or S, and the number of heteroatoms is 1-3; ^Ra and ^Rb are independently halogen, _C1 - _C30 alkyl, _C3 - _C30 cycloalkyl, _C2 - _C30 alkenyl, -O-( _C2 - _C30 alkenyl), _C6 - _C30 aryl, _C1 - _C30 alkoxy, Ra ^-1 and Ra ^-2 are independently _C1 - _C30 alkyl groups; R ¹ and R ¹ 'are independently R ^1-1 and R ^1-2 are independently C ₁ -C ₃₀ alkyl, C ₆ -C ₃₀ aryl, or C ₁ -C ₃₀ alkyl substituted with phenyl; R ² and R ² 'are independently H, C ₁ -C ₃₀ alkyl, C ₄ -C ₃₀ cycloalkenyl, C ₆ -C ₃₀ aryl, or C ₆ -C ₃₀ aryl substituted by one or more R ^2-1 ; R ^2-1 is independently C ₁ -C ₃₀ alkyl, C _{1 -C 30} alkoxy, C ₆ -C ₃₀ aryl, halogen, C ₁ -C ₃₀ alkyl substituted by one or more halogens, R ^2-1-1 or R ^2-1-2 is independently a C ₁ -C ₃₀ alkyl group; X and X' are independently halogen; The compound of formula I is the same as or different from the compound of formula II; when they are different, the atomic number of X in the compound of formula I is not less than the atomic number of X' in the compound of formula II. 2. The preparation method according to claim 1, characterized in that one or more of the following conditions are met: (1) When Ring A and Ring A' are independently C ₆ -C ₁₀ aryl and C ₆ -C ₁₀ aryl substituted by one or more ^Ra , the C ₆ -C ₁₀ aryl and the C _{6 -C 10 aryl} substituted by one or more ^Ra are independently phenyl or naphthyl; (2) When Ring A and Ring A' are independently 5-10 membered heteroaryl or 5-10 membered heteroaryl substituted by one or more R ^b , the 5-10 membered heteroaryl is pyridyl or thienyl; (3) When ^Ra and ^Rb are independently halogen, the halogen is F, Cl, Br or I; (4) When ^Ra and ^Rb are independently _C1 - _C30 alkyl, the _C1 - _C30 alkyl is _{C1-C10 alkyl} ; for example, _C1 - _C6 alkyl, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; (5) When ^Ra and ^Rb are independently _C3 - _C30 cycloalkyl, _{the C3-C30 cycloalkyl} is _C3 - _C10 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; (6) When ^Ra and ^Rb are independently _C2 - _C30 alkenyl, the _C2 - _C30 alkenyl is _C2 - _C10 alkenyl, such as _C2 - _C6 alkenyl, and such as vinyl, propenyl, allyl or _-CH2- ( _CH2 ) _2CH = _CH2 ; (7) When ^Ra and ^Rb are independently -O-(C2- _C30 alkenyl), the C2 _{- C30} alkenyl is _C2 - _C10 alkenyl _, such as _C2 - _C6 alkenyl, and also such as vinyl, propenyl, allyl or _-CH2- ( _CH2 ) _2CH = _CH2 ; (8) When ^Ra and ^Rb are independently _{C6 - C30} aryl, the _C6 - _C30 aryl is C6- _C10 aryl, such as phenyl or naphthyl; (9) When ^Ra and ^Rb are independently C1 _{- C30} alkoxy groups, the C1 _{-C30 alkoxy groups are C1-C10 alkoxy groups, such as C1-C6 alkoxy groups , and also} such as methoxy, ethoxy, isopropoxy, and tert-butoxy groups; (10) When Ra ^-1 and Ra ^-2 are independently _C1 - _C30 alkyl, the _C1 - _C30 alkyl is _C1 - _C10 alkyl; for example, _C1 - _C6 alkyl, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; (11) When R ^1-1 and R ^1-2 are independently C ₁ -C ₃₀ alkyl groups, the C ₁ -C ₃₀ alkyl groups are C ₁ -C ₁₀ alkyl groups; for example, C ₁ -C ₆ alkyl groups, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl groups; (12) When R ^1-1 and R ^1-2 are independently C ₆ -C ₃₀ aryl groups, the C ₆ -C ₃₀ aryl groups are C ₆ -C ₁₀ aryl groups, such as phenyl or naphthyl; (13) When R ^1-1 and R ^1-2 are independently C ₁ -C ₃₀ alkyl substituted by phenyl; the C ₁ -C ₃₀ alkyl in the C ₁ -C ₃₀ alkyl substituted by phenyl is C ₁ -C ₁₀ alkyl, for example C ₁ -C ₆ alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; (14) When R ² and R ² ' are independently C ₁ -C ₃₀ alkyl groups, the C ₁ -C ₃₀ alkyl group is a C ₁ -C ₁₀ alkyl group; for example, a C ₁ -C ₆ alkyl group, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl group; (15) When R ² and R ² 'are independently C ₃ -C ₃₀ cycloalkenyl, the C ₁ -C ₃₀ cycloalkenyl is C ₃ -C ₁₀ cycloalkenyl; for example, C ₃ -C ₆ cycloalkenyl, for example For example, (16) When R ² and R ² ' are independently C ₆ -C ₃₀ aryl or C ₆ -C ₃₀ aryl substituted by one or more R _2-1 , the C ₆ -C ₃₀ aryl or the C ₆ -C ₃₀ aryl substituted by one or more R ^2-1 is C ₆ -C ₁₀ aryl, such as phenyl or ^naphthyl _. (17) When R ^2-1 is independently a C ₁ -C ₃₀ alkyl group or a C ₁ -C ₃₀ alkyl group substituted by one or more halogens, the C ₁ -C ₃₀ alkyl group or the C ₁ -C ₃₀ alkyl group substituted by one or more halogens is a C ₁ -C ₁₀ alkyl group; for example, a C _{1 -C 6} alkyl group, for example, methyl, ethyl, _n -propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl group; (18) When R ^2-1 is a C ₁ -C ₃₀ alkoxy group, the C ₁ -C ₃₀ alkoxy group is a C ₁ -C ₁₀ alkoxy group, such as a C ₁ -C ₆ alkoxy group, and also such as a methoxy group, an ethoxy group, an isopropoxy group, and a tert-butoxy group; (19) When R ^2-1 is a C ₆ -C ₃₀ aryl group, the C ₆ -C ₃₀ aryl group is a C ₆ -C ₁₀ aryl group, such as phenyl or naphthyl; (20) When R ^2-1 is halogen or C ₁ -C ₃₀ alkyl substituted by one or more halogens, the halogen or the halogen in the C ₁ -C ₃₀ alkyl substituted by one or more halogens is F, Cl, Br or I; (21) When R ^2-1 is a C ₁ -C ₃₀ alkyl group substituted by one or more halogens, the C ₁ -C ₃₀ alkyl group is a C ₁ -C ₆ alkyl group, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl or n-hexyl; for example, ethyl, n-propyl, isopropyl or tert-butyl; (22) When R ^2-1 is a C ₁ -C ₃₀ alkyl group substituted by one or more halogens, the number of the halogens is 1, 2 or 3; for example, trifluoromethyl; (23) When R ^2-1-1 or R ^2-1-2 is independently a C ₁ -C ₃₀ alkyl group, the C ₁ -C ₃₀ alkyl group is a C ₁ -C ₁₀ alkyl group; for example, a C ₁ -C ₆ alkyl group, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group or an n-hexyl group; for example, a methyl group; (24) When X and X' are independently halogen, the halogen is F, Cl, Br or I, for example Br or I. 3. The preparation method according to claim 2, characterized in that one or more of the following conditions are met: (1) Ring A and Ring A' are independently (2) R ¹ and R ¹ ′ are independently -OBn or -CO ₂ Ph; (3) R ² and R ² 'are independently H, methyl, phenyl, naphthyl, (4) When the compound of formula I is different from the compound of formula II, X in the compound of formula I is I, and R ¹ is -OBn; X' in the compound of formula II is Br, and R ^1' is -CO ₂ Ph; (5) In the compound of formula I, R ² is located at the para or meta position relative to X; in the compound of formula II, R ² ' is located at the para or meta position relative to X'; (6) When the compound of formula I is different from the compound of formula II, the compound of formula I, the compound of formula II and the corresponding compound of formula III are any of the following groups: or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof, or an enantiomer thereof; (7) 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: 4. The preparation method according to claim 1, characterized in that the chiral nitrogen ligand is a compound as shown in formula IV or an enantiomer thereof, wherein R ⁴ and R ⁵ are independently H, C ₁ -C ₁₀ alkyl, C ₃ -C ₁₅ cycloalkyl, C ₆ -C ₁₀ aryl, or C ₁ -C ₁₀ alkyl substituted with phenyl; Alternatively, ^R4 and ^R5 together with the attached carbon form: Where n is 0-6, such as 1 or 2; R ⁶ and R ⁷ are independently H, phenyl or naphthyl, and R ⁶ and R ⁷ are not H at the same time; Alternatively, ^R6 and ^R7 together with the attached carbon form: 5. The preparation method according to claim 4, characterized in that one or more of the following conditions are met: (1) When R ⁴ and R ⁵ are C ₁ -C ₁₀ alkyl, the C ₁ -C ₁₀ alkyl is C ₁ -C ₆ alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl or -CH(CH ₂ CH ₃ ) ₂ ; (2) When R ⁴ or R ⁵ is a C ₃ -C ₁₅ cycloalkyl group, the C ₃ -C ₁₅ cycloalkyl group is a C ₃ -C ₁₂ cycloalkyl group, such as cyclopropyl, cyclopentyl, cyclohexyl, and cyclooctyl; (3) When R ⁴ or R ⁵ is a C ₆ -C ₁₀ aryl group, the C ₆ -C ₁₀ aryl group is a phenyl group or a naphthyl group; (4) When R ⁴ or R ⁵ is a C ₁ -C ₁₀ alkyl group substituted by a phenyl group; the C ₁ -C ₁₀ alkyl group is a C ₁ -C ₆ alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl or -CH(CH ₂ CH ₃ ) ₂ ; (5) ^R6 and ^R7 are independently H or phenyl; for example, ^R6 is independently H and ^R7 is independently phenyl; (6) The electrolyte is one or more of a quaternary ammonium salt, a sodium salt and a lithium salt; (7) The solvent is one or more of an amide solvent, a halogenated hydrocarbon solvent, a nitrile solvent and an alcohol solvent; (8) The Co salt is one or more of a Co(I) compound, a Co(II) compound and a Co(III) compound. 6. The preparation method according to claim 4, characterized in that the chiral nitrogen ligand 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 as shown below, or enantiomers thereof; preferably L16 or L12, or enantiomers thereof, 7. The preparation method according to claims 1-6, characterized in that one or more of the following conditions are met: (1) When the compound of formula I is different from the compound of formula II, the chiral nitrogen ligand is preferably L16 or its enantiomer; when the compound of formula I is the same as the compound of formula II, the chiral nitrogen ligand is preferably L12 or its enantiomer; (2) 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, 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; most preferably stainless steel and nickel; (3) When the compound represented by Formula I is the same as the compound represented by Formula II, the anode electrode is iron and the cathode electrode is stainless steel; (4) When the compound represented by Formula I is different from the compound represented by Formula II, the anode electrode is iron and the cathode electrode is nickel; (5) The quaternary ammonium salt is one or more of Et ₄ NBF ₄ , n-Bu ₄ NBF ₄ , Et ₄ NPF ₆ , n-Bu ₄ NPF ₆ , Et ₄ NClO ₄ , n-Bu ₄ NClO ₄ , Et ₄ NOAc, n-Bu ₄ NOAc, Et ₄ NOTs, n-Bu ₄ NOTs, n-Bu ₄ NI and H ₄ NCl; preferably one or more of n-Bu ₄ NBF ₄ , n-Bu ₄ NPF ₆ , Et ₄ NOTs and n-Bu ₄ NI; (6) The sodium salt is one or more of NaCl, NaBr, NaI and NaOAc; preferably NaI; (7) the lithium salts LiBr and/or LiCl; (8) The solvent is one or more of DMF, DMAc, dichloromethane, chloroform, acetonitrile, methanol, ethanol and isopropanol; preferably one or more of DMF, DMAc and acetonitrile; most preferably DMF or DMAc; (9) The Co salt is one or more of CoCl(PPh ₃ ) ₂ ), CoI ₂ , CoCl ₂ , CoBr ₂ ·glyme, Co(OAc) ₂ , Co(C ₂ O ₄ ) ₂ and Co(acac) ₃ ; preferably one or more of CoI ₂ , CoCl ₂ , CoBr ₂ ·glyme, Co(OAc) ₂ , CoCl(PPh ₃ ) ₂ , Co ₂ (acac) ₃ , Co(C ₂ O ₄ ) ₂ ; most preferably CoI ₂ ; (10) The electrochemical asymmetric coupling reaction further includes adding a desiccant, wherein the desiccant is one or more of Na ₂ SO ₄ , MgSO ₄ and molecular sieve, preferably molecular sieve; (11) The molar concentration of the compound of formula I in the solvent is 0.01-1 mol/L, preferably 0.02-0.5 mol/L, more preferably 0.06-0.25 mol/L; (12) The molar concentration of the compound represented by Formula II in the solvent is 0.01-1 mol/L, preferably 0.02-0.8 mol/L, and more preferably 0.06-0.5 mol/L; (13) The molar concentration of the electrolyte in the solvent is 0.01-1 mol/L, preferably 0.02-0.6 mol/L, more preferably 0.06-0.25 mol/L; (14) The molar ratio of the electrolyte to the compound of formula I is 1:1-1:10, preferably 1:1-2:5; (15) When the compound of formula I and the compound of formula II are different, the molar ratio of the compound of formula I to the compound of formula II is 1:1-5:1, preferably 1:1-2:1; (16) When the compound of formula I is the same as the compound of formula II, the molar ratio of the total amount of the compound of formula I and the compound of formula II to the chiral nitrogen ligand is 1:1-10:1, preferably 5:1-7:1; (17) When the compound of formula I is different from the compound of formula II, the molar ratio of the compound of formula I to the chiral nitrogen ligand is 1:1-10:1, preferably 5:1-7:1; (18) The molar ratio of the Co salt to the chiral nitrogen ligand is 1:1-1:5, preferably 1:2; (19) The current value of the electrochemical asymmetric coupling reaction is 0.1-20 mA, preferably 1-6 mA; (20) The electrochemical asymmetric coupling reaction is preferably carried out at 0-150°C, more preferably at 0-80°C, preferably at 10-30°C; (21) When the chiral nitrogen ligand is a compound as shown in Formula IV, the compound as shown in Formula III is in R configuration; when the chiral nitrogen ligand is an enantiomer of the compound as shown in Formula IV, the compound as shown in Formula III is in S configuration. 8. A compound selected from the following structures: 9. Use of the compound as claimed in claim 8 in asymmetric synthesis, preferably as a catalyst in the electrochemical asymmetric coupling reaction as claimed in claim 7. 10. A compound of formula V or an enantiomer thereof, the structure of which is shown below, in, ^R8 is H, _C1 - _C10 alkyl, _C3 - _C15 cycloalkyl, _C6 - _C10 aryl, or _C1 - _C10 alkyl substituted by phenyl; X is halogen. 11. The compound or enantiomer thereof according to claim 10, characterized in that one or more of the following conditions are met: (1) X is Br or I, preferably I; (2) When R ⁸ is C ₁ -C ₁₀ alkyl or C ₁ -C ₁₀ alkyl substituted with phenyl, the C ₁ -C 10 alkyl in the C ₁ -C ₁₀ alkyl or C ₁ -C ₁₀ alkyl substituted with phenyl is C ₁ -C ₆ alkyl, such as methyl, ethyl, n _- propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl or -CH(CH ₂ CH ₃ ) ₂ ; (3) When R ⁸ is a C ₃ -C ₁₅ cycloalkyl group, the C ₃ -C ₁₅ cycloalkyl group is a C ₃ -C ₁₂ cycloalkyl group, such as cyclopropyl, cyclopentyl, cyclohexyl, and cyclooctyl; (4) When R ⁸ is a C ₆ -C ₁₀ aryl group, the C ₆ -C ₁₀ aryl group is a phenyl group or a naphthyl group. 12. The compound or enantiomer thereof according to claim 10, characterized in that the compound or enantiomer thereof as shown in formula V is a compound or enantiomer thereof as shown in formula VI, Among them, X is F, Cl, Br, I, preferably I. 13. Use of the compound of formula V as claimed in any one of claims 10 to 12 or its enantiomer in asymmetric synthesis, preferably as a catalyst in the electrochemical asymmetric coupling reaction as claimed in claim 7.