Preparation method of axially chiral biaryl diphenol derivative

Abstract

The invention relates to the technical field of organic and pharmaceutical synthesis, and discloses a preparation method of an axially chiral biaryl diphenol derivative, which specifically comprises the following steps: under the condition of direct current, by taking chiral phosphoric acid (CPA) as a catalyst, promoting a reaction between a hydroquinone derivative as shown in a formula (II) and a naphthol derivative as shown in a formula (III) in an electrolyte A and a solvent B to obtain the axially chiral biaryl diphenol derivative. And after the reaction is finished, separating and purifying to obtain the axially chiral biaryl diphenol derivative as shown in the formula (I). In the traditional method, p-benzoquinone and naphthol are used as raw materials and are obtained through nucleophilic addition reaction, which has many defects. The axially chiral compound is obtained through an electrochemical method, only hydrogen is generated in the reaction, environmental pollution is small, the atom utilization rate is high, and the requirements of current green chemistry are met.

Description

Technical Field

[0001] The invention relates to the technical field of organic and pharmaceutical synthesis, and in particular to a method for preparing an axially chiral biaryl diphenol derivative. Background Art

[0002] Biaryl diphenol compounds are widely present in a variety of biologically active natural products, drugs and polymer materials, and are widely used in the development of chiral ligands and asymmetric transformation organic catalysts. Among them, axially chiral biaryl phosphine compounds have attracted much attention due to their superior skeleton structure. Therefore, the construction of axially chiral biaryl diphenol derivatives has become an important research direction in organic synthetic chemistry.

[0003] The main method for synthesizing axial chiral biaryl diphenol derivatives is to use benzoquinone and naphthol derivatives as substrates, but the atomic utilization rate of this method is low, and the quinone structure is unstable and easy to deteriorate. In 2016, Mauro's group developed a quinine-catalyzed asymmetric coupling reaction of 2-naphthol and quinone derivatives (Angew. Chem. Int. Ed. 2016, 55, 6525–6529.), with a reaction yield of 60-99% and an er value of 92:8. In 2020, Gavin's group found that a small modular tetrameric peptide of β-dimethylaminoalanine (DMAA) with Lewis basic residues can selectively couple with naphthol and ester quinone compounds to generate a non-C2-symmetric BINOL-type scaffold with good yield and enantioselectivity, with an enantiomeric ratio (er) of up to 93:7 (Angew. Chem. Int. Ed. 2020, 59, 2875–2880.). However, in these reactions, quinones are prepared by oxidation of phenols with stoichiometric amounts of oxidants, which is not only costly but also requires high energy consumption when the reaction is carried out at low temperatures. Currently, relatively few reports have been published on the preparation of axially chiral biaryl diphenol derivatives.

[0004] Organic electrochemical catalysis shows good prospects in this field, and its advantages are mainly reflected in the high efficiency, environmental protection and sustainability of the catalytic process. In particular, by using phenolic compounds as substrates instead of traditional quinone compounds, it can not only effectively shorten the synthesis time and avoid the generation of waste, but also significantly reduce the dependence on dangerous and harmful reagents. This method is in line with the principles of green chemistry and meets the requirements of environmentally friendly synthesis. At the same time, phenolic substrates have a lower redox potential, which makes it easier to stimulate the reaction in electrochemical catalysis, which helps to improve the catalytic efficiency. Summary of the invention

[0005] In view of the above technical problems existing in the prior art, the object of the present invention is to provide a method for efficiently preparing axially chiral biaryl diphenol derivatives by synergistically catalyzing the asymmetric free radical coupling reaction of hydroquinone derivatives and naphthol derivatives with electro / chiral phosphoric acid.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] A method for preparing an axially chiral biaryl diphenol derivative comprises the following steps:

[0008] Step 1: add chiral phosphoric acid (CPA), a hydroquinone derivative as shown in formula (II), a naphthol derivative as shown in formula (III), electrolyte A and solvent B to a Shrek tube equipped with a magnet, insert electrodes, stir at room temperature (25° C.) and start the current reaction;

[0009] Step 2: After the reaction is completed, water is added to quench the reaction, and the product is extracted with dichloromethane. The separated organic layer is concentrated under reduced pressure, and the obtained residue is separated by column chromatography to obtain a chiral biaryl diphenol derivative as shown in formula (I);

[0010] The specific reaction route is as follows:

[0011]

[0012] In formula (II), R 1 For CO2R 3 OR 3 )2,R 3 is methyl, ethyl, n-propyl, isopropyl, n-butyl, benzyl or substituted benzyl; in formula (III), R 2 It is hydrogen, halogen, methoxy, cyano or substituted aryl.

[0013] Preferably, in step 1, the electrolyte A is n-Bu4NBF4; and the solvent B is at least one of dichloromethane and 1,2-dichloroethane.

[0014] Preferably, in the step 1, the structural formula of the chiral phosphoric acid is as follows:

[0015]

[0016] Preferably, in the step 1, the molar ratio of the hydroquinone derivative, the naphthol derivative, the electrolyte A and the chiral phosphoric acid is 1:(1.0-1.2):2:(0.15-0.2).

[0017] Preferably, in step 1, the reaction voltage for the current reaction is set to 1.8-2.0V.

[0018] Preferably, in step 1, the reaction time of the current reaction is 12 to 24 hours.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] Compared with the traditional reaction, the present invention:

[0021] 1. A method for efficiently preparing axially chiral biaryl diphenol derivatives by catalyzing the asymmetric free radical addition reaction of hydroquinone derivatives and naphthol derivatives through electro / chiral phosphoric acid synergistic catalysis, with a yield of up to 95% and a product ee value of up to 97%;

[0022] 2. It has the characteristics of low energy consumption, high atomic economy and low green pollution;

[0023] 3. It has important application prospects in the preparation of new catalysts and drug modification. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The present invention provides a cyclic voltammetry curve of 7-methoxy-2-naphthol (IIIa) and methyl 2,5-dihydroxybenzoate (IIa) in the preparation method of an axially chiral biaryl diphenol derivative. DETAILED DESCRIPTION

[0025] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0026] Example 1: Preparation of methyl 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Iaa)

[0027]

[0028] Into a Shrek tube equipped with a magnet, methyl 2,5-dihydroxybenzoate (16.8 mg, 0.1 mmol), 7-methoxy-2-naphthol (20.9 mg, 0.12 mmol), chiral phosphoric acid CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) were added in sequence, and the electrode was inserted, stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 29.95 mg of methyl 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Iaa) as a white solid with a melting point of 179-180° C., a yield of 88%, and an ee value of 93%.

[0029] Example 2: Preparation of ethyl 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Iba)

[0030]

[0031] To a Shrek tube equipped with a magnet, ethyl 2,5-dihydroxybenzoate (18.2 mg, 0.1 mmol), 7-methoxy-2-naphthol (20.9 mg, 0.12 mmol), chiral phosphoric acid CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) were added in sequence, and the electrode was inserted, stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 33.62 mg of ethyl 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Iba) as a white solid with a melting point of 202-203° C., a yield of 95%, and an ee value of 92%.

[0032] Example 3: Preparation of 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)propyl benzoate (Ica)

[0033]

[0034] To a Shrek tube equipped with a magnet, add 2,5-dihydroxybenzoic acid propyl ester (19.6 mg, 0.1 mmol), 7-methoxy-2-naphthol (20.9 mg, 0.12 mmol), chiral phosphoric acid CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) in sequence, insert an electrode, stir at room temperature (25 ° C) and pass a direct current of 1.8 V to react for 12 hours. The reactant is quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 31.9 mg of 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoic acid propyl ester (Ica) as a white solid with a melting point of 223-224° C., a yield of 89%, and an ee value of 92%.

[0035] Example 4: Preparation of 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoic acid isopropyl ester (Ida)

[0036]

[0037] Into a Shrek tube equipped with a magnet, add isopropyl 2,5-dihydroxybenzoate (19.6 mg, 0.1 mmol), 7-methoxy-2-naphthol (20.9 mg, 0.12 mmol), CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) in sequence, insert an electrode, stir at room temperature (25 ° C) and pass a direct current of 1.8 V to react for 12 hours. The reactant is quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 31.6 mg of isopropyl 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Ida) as a light yellow solid with a melting point of 195-196° C., a yield of 88%, and an ee value of 92%.

[0038] Example 5: Preparation of 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoic acid n-butyl ester (Iea)

[0039]

[0040] Into a Shrek tube equipped with a magnet, 2,5-dihydroxybenzoic acid n-butyl ester (21.0 mg, 0.1 mmol), 7-methoxy-2-naphthol (20.9 mg, 0.12 mmol), chiral phosphoric acid CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) were added in sequence, and the electrode was inserted, stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 32.5 mg of n-butyl 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Iea) as a light yellow solid with a melting point of 207-208° C., a yield of 85%, and an ee value of 90%.

[0041] Example 6: Preparation of 4-bromobenzyl-3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Ifa)

[0042]

[0043] Into a Shrek tube equipped with a magnet, 4-bromobenzyl-2,5-dihydroxybenzoate (32.3 mg, 0.1 mmol), 7-methoxy-2-naphthol (20.9 mg, 0.12 mmol), CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) were added in sequence, and the electrode was inserted, stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 41.5 mg of 4-bromobenzyl 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Ifa) as a light yellow solid with a melting point of 201-202° C., a yield of 84%, and an ee value of 92%.

[0044] Example 7: Preparation of 3-bromobenzyl-3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Iga)

[0045]

[0046] Into a Shrek tube equipped with a magnet, 3-bromobenzyl-2,5-dihydroxybenzoate (32.3 mg, 0.1 mmol), 7-methoxy-2-naphthol (20.9 mg, 0.12 mmol), CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) were added in sequence, and the electrode was inserted, stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 34.1 mg of 3-bromobenzyl 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Iga) as a light yellow solid with a melting point of 189-190° C., a yield of 69%, and an ee value of 95%.

[0047] Example 8: Preparation of 2-bromobenzyl-3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Iha)

[0048]

[0049] Into a Shrek tube equipped with a magnet, 2-bromobenzyl-2,5-dihydroxybenzoate (32.3 mg, 0.1 mmol), 7-methoxy-2-naphthol (20.9 mg, 0.12 mmol), CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) were added in sequence, and the electrode was inserted, stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 36.5 mg of 2-bromobenzyl 3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)benzoate (Iha) as a light yellow solid with a melting point of 197-198° C., a yield of 74%, and an ee value of 97%.

[0050] Example 9: Preparation of ethyl 2-(7-(4-chlorophenyl)-2-hydroxynaphthalen-1-yl)-3,6-dihydroxybenzoate (Ibb)

[0051]

[0052] To a Shrek tube equipped with a magnet, ethyl 2,5-dihydroxybenzoate (18.2 mg, 0.1 mmol), 7-(4-chlorophenyl)-2-hydroxynaphthalene (30.6 mg, 0.12 mmol), CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) were added in sequence, and the electrode was inserted, stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 38.6 mg of ethyl 2-(7-(4-chlorophenyl)-2-hydroxynaphthalen-1-yl)-3,6-dihydroxybenzoate (Ibb) as a light yellow solid with a melting point of 212-213° C., a yield of 89%, and an ee value of 90%.

[0053] Structural characterization of (Ibb): 1 H NMR (600MHz, DMSO-d6, ppm) δ9.29(s,1H),9.27(s,1H),8.54(s,1H),7.86(d,J=8.4Hz,1H),7.76(d,J=9.0Hz,1H),7.55–7.49(m, 5H),7.38(s,1H),7.20(d,J=9.0Hz,1H),6.92(d,J=9.0Hz,1H),6.83(d,J=8.4Hz,1H),3.65–3.59(m,2H),0.37(t,J=6.6Hz,3H). 13 C NMR (150MHz, DMSO-d6, ppm) δ167.8,153.4,148.5,148.3,140.3,136.2,134.5,132.6,129.4,128.9 ,128.8,128.5,127.5,123.1,123.0,122.2,121.5,119.0,118.6,117.2,116.6,59.9,13.3.Chiral HPLC: The ee was determined by DaicelChiralcel IA, Hexanes / IPA=85 / 15, 1.0mL / min, λ=254nm, T=25℃, t(major)=42.869min, t(minor)=18.116min.HRMS(ESI):calcd for C 25 H 20 ClO5[M+H] + 435.0994, found 435.1007.

[0054] Example 10: Preparation of ethyl 2-(6-cyano-2-hydroxynaphthalen-1-yl)-3,6-dihydroxybenzoate (Ibc)

[0055]

[0056] To a Shrek tube equipped with a magnet, ethyl 2,5-dihydroxybenzoate (18.2 mg, 0.1 mmol), 6-hydroxy-2-naphthocarbonitrile (20.3 mg, 0.12 mmol), CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), dichloromethane (5.0 mL) were added in sequence, and electrodes were inserted. The mixture was stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 30.1 mg of ethyl 2-(6-cyano-2-hydroxynaphthalen-1-yl)-3,6-dihydroxybenzoate (Ibc) as a light yellow solid, melting point: 167-168° C., yield: 63%, ee value: 96%.

[0057] Example 11: Preparation of ethyl 2-(7-bromo-2-hydroxynaphthalen-1-yl)-3,6-dihydroxybenzoate (Ibd)

[0058]

[0059] To a Shrek tube equipped with a magnet, ethyl 2,5-dihydroxybenzoate (18.2 mg, 0.1 mmol), 7-bromo-2-naphthol (26.5 mg, 0.12 mmol), CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), and dichloromethane (5.0 mL) were added in sequence, and electrodes were inserted. The mixture was stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 37.3 mg of ethyl 2-(7-bromo-2-hydroxynaphthalen-1-yl)-3,6-dihydroxybenzoate (Ibd) as a red solid with a melting point of 185-186° C., a yield of 93%, and an ee value of 91%.

[0060] Example 12: Preparation of ethyl 3,6-dihydroxy-2-(2-hydroxy-8-iodonaphthalen-1-yl)benzoate (Ibe)

[0061]

[0062] To a Shrek tube equipped with a magnet, ethyl 2,5-dihydroxybenzoate (18.2 mg, 0.1 mmol), 8-iodo-2-naphthol (32.4 mg, 0.12 mmol), CPA1 (11.3 mg, 15 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), and dichloromethane (5.0 mL) were added in sequence, and electrodes were inserted. The mixture was stirred at room temperature (25°C) and a direct current of 1.8 V was applied to react for 12 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 40.5 mg of ethyl 3,6-dihydroxy-2-(2-hydroxy-8-iodonaphthalen-1-yl)benzoate (Ibe) as a brown solid with a melting point of 171-172° C., a yield of 90%, and an ee value of 95%.

[0063] Structural characterization of (Ibe): 1 H NMR (400MHz, Acetone-d6, ppm) δ10.79(s,1H),8.16(d,J=7.2Hz,1H),8.04(s,1H),7.91(d,J=8.0Hz,1H),7.83(d,J=8 .8Hz,1H),7.33–7.30(m,2H),7.12(d,J=8.8Hz,1H),7.00–6.94(m,2H),3.76(q,J=7.2Hz,2H),0.32(t,J=7.2Hz,3H). 13 C NMR (100MHz, Acetone-d6, ppm) δ171.0,156.4,153.4,150.1,142.3,132.8,130.2,130.2,1 30.1,123.5,122.9,121.9,118.6,118.6,118.5,115.7,89.0,60.3,12.1.ChiralHPLC:The ee was determined by Daicel Chiralcel AD-H, Hexanes / IPA=80 / 20, 1.0mL / min, λ=254nm, T=25℃, t(major)=16.203min, t(minor)=29.347min.HRMS(ESI):calcdfor C 19 H 16 IO5[M+H] + 451.0037, found 451.0025.

[0064] Example 13: Preparation of dimethyl (3,6-dihydroxy-2-(2-hydroxynaphthalen-1-yl)phenyl)phosphate (Vaf)

[0065]

[0066] To a Shrek tube equipped with a magnet, dimethyl (2,5-dihydroxyphenyl) phosphate (21.8 mg, 0.1 mmol), β-naphthol (14.4 mg, 0.1 mmol), CPA2 (13.3 mg, 20 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), 1,2-dichloroethane (5.0 mL) were added in sequence, and electrodes were inserted, stirred at room temperature (25°C) and reacted with a direct current of 2.0 V for 24 hours. The reactants were quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 28.4 mg of dimethyl (3,6-dihydroxy-2-(2-hydroxynaphthalen-1-yl)phenyl)phosphate (Vaf) as a reddish brown solid with a melting point of 232-233° C., a yield of 79%, and an ee value of 91%.

[0067] Example 14: Preparation of diethyl (3,6-dihydroxy-2-(2-hydroxynaphthalen-1-yl)phenyl)phosphate (Vbf)

[0068]

[0069] To a Shrek tube equipped with a magnet, diethyl (2,5-dihydroxyphenyl) phosphate (24.6 mg, 0.1 mmol), β-naphthol (14.4 mg, 0.1 mmol), CPA2 (13.3 mg, 20 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), 1,2-dichloroethane (5.0 mL) were added in sequence, and electrodes were inserted. The mixture was stirred at room temperature (25°C) and a direct current of 2.0 V was applied to react for 24 hours. The reactants were quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 31.4 mg of diethyl (3,6-dihydroxy-2-(2-hydroxynaphthalen-1-yl)phenyl)phosphate (Vbf) as a reddish brown solid with a melting point of 214-215° C., a yield of 81%, and an ee value of 87%.

[0070] Example 15: Preparation of diisopropyl (3,6-dihydroxy-2-(2-hydroxynaphthalen-1-yl)phenyl) phosphate (Vcf)

[0071]

[0072] Into a Shrek tube equipped with a magnet, diisopropyl (2,5-dihydroxyphenyl) phosphate (24.6 mg, 0.1 mmol), β-naphthol (14.4 mg, 0.1 mmol), CPA2 (13.3 mg, 20 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), 1,2-dichloroethane (5.0 mL) were added in sequence, and the electrode was inserted, stirred at room temperature (25°C) and a direct current of 2.0 V was applied to react for 24 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 32.8 mg of diisopropyl (3,6-dihydroxy-2-(2-hydroxynaphthalen-1-yl)phenyl) phosphate (Vcf) as a brown solid with a melting point of 187-188° C., a yield of 79%, and an ee value of 89%.

[0073] Example 16: Preparation of dibutyl (3,6-dihydroxy-2-(2-hydroxynaphthalen-1-yl)phenyl) phosphate (Vdf)

[0074]

[0075] To a Shrek tube equipped with a magnet, dibutyl (2,5-dihydroxyphenyl) phosphate (30.2 mg, 0.1 mmol), β-naphthol (14.4 mg, 0.1 mmol), CPA2 (13.3 mg, 20 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), 1,2-dichloroethane (5.0 mL) were added in sequence, and the electrode was inserted, stirred at room temperature (25°C) and a direct current of 2.0 V was applied to react for 24 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 32.8 mg of dibutyl (3,6-dihydroxy-2-(2-hydroxynaphthalen-1-yl)phenyl) phosphate (Vdf) as a brown solid with a melting point of 236-237° C., a yield of 79%, and an ee value of 89%.

[0076] Example 17: Preparation of diethyl (3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)phenyl)phosphate (Vba)

[0077]

[0078] To a Shrek tube equipped with a magnet, diethyl (2,5-dihydroxyphenyl) phosphate (24.6 mg, 0.1 mmol), 7-methoxy-2-naphthol (17.4 mg, 0.1 mmol), CPA2 (13.3 mg, 20 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), 1,2-dichloroethane (5.0 mL) were added in sequence, and electrodes were inserted. The mixture was stirred at room temperature (25°C) and a direct current of 2.0 V was applied to react for 24 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 35.4 mg of diethyl (3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)phenyl)phosphonate (Vba) as a reddish brown solid with a melting point of 168-169° C., a yield of 85%, and an ee value of 93%.

[0079] Example 18: Preparation of dibutyl-(3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)) phosphate (Vda)

[0080]

[0081] To a Shrek tube equipped with a magnet, dibutyl (2,5-dihydroxyphenyl) phosphate (30.2 mg, 0.1 mmol), 7-methoxy-2-naphthol (17.4 mg, 0.1 mmol), CPA2 (13.3 mg, 20 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), 1,2-dichloroethane (5.0 mL) were added in sequence, and electrodes were inserted. The mixture was stirred at room temperature (25°C) and a direct current of 2.0 V was applied to react for 24 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain 41.2 mg of dibutyl-(3,6-dihydroxy-2-(2-hydroxy-7-methoxynaphthalen-1-yl)) phosphate (Vda) as a light yellow solid with a melting point of 163-164° C., a yield of 87%, and an ee value of 92%.

[0082] Structural characterization of (Vda): 1 H NMR (400 MHz, Acetone-d 6,ppm)δ11.13(s,1H),7.85(s,1H),7.73(d,J=8.8Hz,2H),7.19(d,J=8.8Hz,1H ),7.07(d,J=8.8Hz,1H),6.96–6.89(m,3H),6.53(s,1H),3.99–3.84(m,2H), 3.68(s,3H),3.43–4.40(m,1H),3.24–3.20(m,1H),1.63–1.55(m,2H),1.34– 1.28(m,3H),0.90(d,J=7.2Hz,3H),0.85–0.71(m,3H),0.66(t,J=7.2Hz,3H). 13 C NMR (100MHz, Acetone-d6, ppm) δ158.0,157.4,157.4,154.1,148.4,148.2,136.3,129.3,129.2,124.0,123.9,123.8,123.3,123.3,1 18.6,118.5,115.8,114.3,113.9,110.7,108.9,104.2,66.1,66.1,65.5,65.4,54.4,32.1,32.0,31.2,31.2,18.4,18.1,13.0,12.8. 31 P NMR (162MHz, Acetone-d6, ppm) δ21.9. Chiral HPLC: The ee was determined by Daicel Chiralcel AD-H, Hexanes / IPA=80 / 20, 1.0mL / min, λ=254nm, T=25℃, t(major)=8.418min, t(minor)=17.038min.HRMS-ESI(m / z):calcd for C 25 H 32 O7P[M+H] + 475.1880, found 475.1892.

[0083] Example 19: Preparation of diethyl (3,6-dihydroxy-2-(2-hydroxy-6-methoxynaphthalen-1-ylphenyl) phosphate (Vbg)

[0084]

[0085] To a Shrek tube equipped with a magnet, diethyl (2,5-dihydroxyphenyl) phosphate (24.6 mg, 0.1 mmol), 6-methoxy-2-naphthol (17.4 mg, 0.1 mmol), CPA2 (13.3 mg, 20 mol%), n-Bu4NBF4 (65.8 mg, 0.2 mmol), 1,2-dichloroethane (5.0 mL) were added in sequence, and electrodes were inserted. The mixture was stirred at room temperature (25°C) and a direct current of 2.0 V was applied to react for 24 hours. The reactant was quenched with water (5 mL) and extracted with dichloromethane (5 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=3:1) to obtain 28.3 mg of diethyl (3,6-dihydroxy-2-(2-hydroxy-6-methoxynaphthalen-1-ylphenyl) phosphate (Vbg) as a reddish brown solid, melting point: 155-156° C., yield: 68%, ee value: 90%.

[0086] In the above embodiments, the structural formula of CPA1 is:

[0087]

[0088] The structural formula of CPA2 is:

[0089]

[0090] Example 20: Cyclic voltammetry curve of Iaa

[0091]

[0092] The voltammetric curves were recorded on a CHI 600E instrument using a 3 mm diameter glassy carbon working electrode, a platinum wire auxiliary electrode, and an Ag / AgCl reference electrode. The electrolyte solution was n-Bu4NBF4 (65.8 mg, 0.2 mmol) dissolved in 5 mL DCM, and the experiment was performed at room temperature (25 °C) with a scan rate of 100 mV / s.

[0093] The cyclic voltammetric behavior of 7-methoxy-2-naphthol (Ⅲa) and methyl 2,5-dihydroxybenzoate (Ⅱa) showed that the oxidation onset potential of Ⅱa was about 1.23V ( Figure 1 , dark blue wave), which is consistent with the starting potential of Ⅲa of 1.42V ( Figure 1 , purple wave) are not much different. It is worth noting that the mixture of Ⅱa and CPA1 shows a slightly reduced signal with an onset potential of 1.31 V ( Figure 1 , green wave), while the mixture of IIIa and CPA1 showed an early signal with an onset potential of 1.27 V ( Figure 1, orange wave). In addition, the onset potential of the mixture of IIIa, IIa and CPA1 is about 1.20 V. These results show that IIIa and IIa can be oxidized at the same time, which is of great significance to the overall design of the present invention, and can improve the reaction efficiency and enhance the catalytic effect.

[0094] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for preparing an axially chiral biaryl diphenol derivative, characterized in that: The following steps are involved: Step 1: add chiral phosphoric acid (CPA), a hydroquinone derivative as shown in formula (II), a naphthol derivative as shown in formula (III), electrolyte A and solvent B to a Shrek tube equipped with a magnet, insert electrodes, stir at room temperature (25° C.) and start the current reaction; Step 2: After the reaction is completed, water is added to quench the reaction, and the product is extracted with dichloromethane. The separated organic layer is concentrated under reduced pressure, and the obtained residue is separated by column chromatography to obtain a chiral biaryl diphenol derivative as shown in formula (I); The specific reaction route is as follows: In formula (II), R 1 For CO2R 3 OR 3 )2,R 3 is methyl, ethyl, n-propyl, isopropyl, n-butyl, benzyl or substituted benzyl; in formula (III), R 2 It is hydrogen, halogen, methoxy, cyano or substituted aryl.

2. The method for preparing an axially chiral biaryl diphenol derivative according to claim 1, characterized in that: In the step 1, the electrolyte A is n-Bu4NBF4; the solvent B is at least one of dichloromethane and 1,2-dichloroethane.

3. The method for preparing an axially chiral biaryl diphenol derivative according to claim 1, characterized in that: In the step 1, the structural formula of the chiral phosphoric acid is as follows:

4. The method for preparing an axially chiral biaryl diphenol derivative according to claim 2, characterized in that: In the step 1, the structural formula of the chiral phosphoric acid is as follows:

5. The method for preparing an axially chiral biaryl diphenol derivative according to claim 1, characterized in that: In the step 1, the molar ratio of the hydroquinone derivative, the naphthol derivative, the electrolyte A and the chiral phosphoric acid is 1:(1.0-1.2):2:(0.15-0.2).

6. The method for preparing an axially chiral biaryl diphenol derivative according to claim 1, characterized in that: In the step 1, the reaction voltage for the current reaction is set to 1.8-2.0V.

7. The method for preparing an axially chiral biaryl diphenol derivative according to claim 1, characterized in that: In the step 1, the reaction time of the current reaction is 12 to 24 hours.

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