CN105111228A - Chiral phosphoric acid with 5,5'-bitetralone skeleton and preparation method thereof - Google Patents

Abstract

The invention belongs to the technical field of organic chemical synthesis. The invention discloses a chiral skeleton of 5,5'-tetralone, a chiral phosphoric acid with a 5,5'-tetralone skeleton, and a chiral phosphoric acid based on 5,5'-tetralone-6 , A method for preparing the chiral phosphoric acid from 6'-diphenol and its substituents. This kind of phosphoric acid not only retains the advantages of good enantioselectivity of traditional chiral phosphoric acid based on BINOL and H ₈ -BINOL, but also shows the same excellent enantioselectivity in some organic reactions; Low disadvantage, showing stronger reactivity than traditional phosphoric acid. In addition, the raw materials and catalysts in the preparation method are cheap and easy to obtain, the synthesis route is short, the process is simple, the conditions are mild, and the method has industrialization potential.

Description

Chiral phosphoric acid with 5,5'-tetralone skeleton and preparation method thereof

technical field

The invention belongs to the technical field of organic chemical synthesis, in particular to a chiral phosphoric acid with a 5,5'-tetralone skeleton, and a 5,5'-tetralone-6,6'-diphenol-based A method for preparing the chiral phosphoric acid and its substitutes, as well as intermediates involved in the preparation process.

Background technique

The development of novel chiral catalysts is an active field in asymmetric synthesis. In 2004, two groups of Akiyama and Terada independently discovered the BINOL-based chiral binaphthylphosphoric acid catalyst (phosphoricacid, Angew.Chem.Int.Ed.2004,43,1566; J.Am.Chem.Soc.2004,126,5356 ), which have been widely used in many organic transformations. The reaction catalyzed by chiral phosphoric acid has a variety of activation modes (Chem.Rev.2014, 114, 9047), and has achieved excellent enantioselectivity, but most of the reaction time is long and the amount of catalyst is large (5%-20% ), which to some extent limits the application of chiral organophosphoric acid in large-scale synthesis and industrial production.

One way to enhance the acidity of phosphoric acid is to make phosphoramide, such as N-triflylphosphoramide (J.Am.Chem.Soc.2006,128,9626), which can significantly increase the catalytic activity, but in most reactions, enantioselectivity Significantly lower (J.Am.Chem.Soc.2013,135,6142). Another way to enhance the acidity is to introduce an electron-withdrawing group such as 3,5-bis(trifluoromethyl)phenyl at the 3,3'-position (ortho to the phenolic hydroxyl group) of binaphthylphosphonic acid, but this in itself would It inevitably changes the volume of the 3,3'-position substituent, thereby affecting the enantioselectivity (Org. Lett. 2010, 12, 4604). However, there is no literature report on the method of introducing an electron-withdrawing group at the 5,5'-position (para-position of the phenolic hydroxyl group) of binaphthylphosphonic acid.

The invention discloses a chiral skeleton of 5,5'-tetralone, a chiral phosphoric acid having a chiral skeleton of 5,5'-tetralone, and a chiral phosphoric acid based on 5,5'-tetralone Hydronaphthalene-6,6'-diol and its substitutes are a method for preparing the chiral phosphoric acid. This kind of phosphoric acid not only retains the advantages of good enantioselectivity of traditional organic chiral phosphoric acids based on BINOL and H ₈ -BINOL, but also overcomes the disadvantage of low catalytic activity.

Contents of the invention

1. Technical problems to be solved

In order to solve the shortcoming of low activity of traditional organic chiral phosphoric acid catalysts, the invention discloses a structure of a newly designed mobile phone phosphoric acid catalyst and a preparation method thereof.

2. Technical solution

The purpose of the present invention is to provide a brand-new chiral skeleton of 5,5'-tetralone;

Another object of the present invention is to provide a chiral phosphoric acid having a 5,5'-binethralone skeleton;

Another object of the present invention is to provide a method for preparing chiral phosphoric acid based on 5,5'-binetralone-6,6'-diol.

The present invention is a compound having general formula shown in (I)～(V):

In the formula: R is selected from H, Cl, Br, I, C6-C19 alkyl, substituted silicon, substituted aryl or conjugated aryl, and the conjugated aryl is naphthyl, anthracenyl, Phenanthrene group; R ¹ is selected from H, Ac, Boc, Bz, MOM, C1～C8 alkyl; X is selected from Cl, Br or I.

The compound represented by formula (I) belongs to chiral organophosphoric acid. Compared with the corresponding traditional phosphoric acid based on BINOL or H ₈ -BINOL, the molecular structure has not changed much, and the same excellent chiral induction ability is retained; but the acidity is stronger, so it overcomes the traditional phosphoric acid catalyst consumption and reaction time. long and other disadvantages. It has achieved excellent enantioselectivity and stronger catalytic activity in Mannich reaction, Biginelli reaction, Friedel-Crafts reaction, Diels-Alder reaction, transfer hydrogenation reaction and other reactions.

The compound structures shown in formulas (I)～(V) have axial chirality, so each compound has two enantiomers, one is R type, and the other is S type, the two enantiomers The mixture of equal amounts becomes a racemate. R-type, S-type and racemate have the same general chemical structure, but have different stereostructures and optical properties. Therefore, the chiral phosphoric acid with 5,5'-tetralone skeleton mentioned in the present invention and the corresponding intermediates involved in the synthesis process actually include R-type, S-type and racemate.

The preparation method of the compound shown in the formula (I) provided by the invention comprises the following steps:

Using Method 1, the steps are:

(1) H ₈ -BINOL is oxidized in an organic solvent (or containing water) through an appropriate catalyst, appropriate temperature and time to obtain 5,5'-tetralone-6 represented by formula (II), 6'-diphenol;

(2) 5,5'-tetralone-6,6'-diol represented by formula (II) undergoes a halogenation reaction to obtain 7,7'-dihalo-5,5 represented by formula (III) '-tetralone-6,6'-diol;

(3) 7,7'-dihalo-5,5'-tetralone-6,6'-diol represented by formula (III), undergoes a coupling reaction to obtain 7 represented by formula (IV), 7'-disubstituted-5,5'-tetralone-6,6'-diol;

(4) 7,7'-disubstituted-5,5'-tetralone-6,6'-diphenol shown in formula (IV), after reacting with phosphorus oxychloride in alkaline conditions, then After hydrolysis, the 7,7'-disubstituted-5,5'-binethalone-6,6'-diphenol-phosphoric acid represented by the formula (I) is obtained;

(5) Purify the compound of formula (I) prepared by silica gel column chromatography;

Or use method 2, the steps are:

(1) 3,3'-disubstituted-H ₈ -BINOL represented by formula (V), in an organic solvent (or containing water), through an oxidation reaction with a suitable catalyst, a suitable temperature and time, to obtain the formula (IV) Represents 7,7'-disubstituted-5,5'-tetralone-6,6'-diol;

(2) 7,7'-disubstituted-5,5'-tetralone-6,6'-diphenol shown in formula (IV), after reacting with phosphorus oxychloride in alkaline conditions, then After hydrolysis, the 7,7'-disubstituted-5,5'-binethalone-6,6'-diphenol-phosphoric acid represented by the formula (I) is obtained;

(3) Purify the compound of formula (I) prepared by silica gel column chromatography;

Or use method three, the steps are:

(1) 3,3'-disubstituted-H ₈ -binaphthol-2,2'-dioxygen compound represented by formula (VI), in organic solvent (or containing water), after proper catalyst action, proper temperature and Oxidation reaction of time to obtain 7,7'-disubstituted-5,5'-binethalone-6,6'-dioxy compound shown in formula (VII);

(2) The 7,7'-disubstituted-5,5'-tetralone-6,6'-dioxy compound shown in (VII) is deprotected to obtain the 7,7 shown in the formula (IV). '-Disubstituted-5,5'-tetralone-6,6'-diol;

(3) 7,7'-disubstituted-5,5'-tetralone-6,6'-diphenol shown in formula (IV), after reacting with phosphorus oxychloride in alkaline conditions, then After hydrolysis, the 7,7'-disubstituted-5,5'-binethalone-6,6'-diphenol-phosphoric acid represented by the formula (I) is obtained;

(4) Purify the prepared compound of formula (I) by silica gel column chromatography.

in:

In the first step of the method, X can be Cl, Br, I, preferably Br; R is a substituted phenyl group or a conjugated aryl group, and the conjugated aryl group is naphthyl, anthracenyl, or phenanthrenyl; in the second step of the method, R is a substituted silicon group, preferably a triphenylsilyl group; in the three steps of the method, R ¹ is an alkyl group of Ac, Boc, Bz, MOM, C1-C8, preferably Me;

The oxidizing agent used in the oxidation reaction of method one step (1) is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and the molar ratio of the H ₈ -BINOL to the oxidizing agent is It is 1:(4～6), preferably 1:4; The coupling reaction condition of method one step (3) is: catalyst is palladium acetate+two (adamantyl) n-butylphosphine, alkali is potassium carbonate, and solvent is Toluene + ethanol, or ethylene glycol dimethyl ether + water.

In the oxidation reaction of method two steps (1), the oxidizing agent is DDQ, and a ferrous chloride catalyst is added, and the molar ratio of the compound of formula (V), the oxidizing agent and the catalyst is 1:(4～6):(0.05～0.2), Preferably 3.6:21.6:0.73.

In the oxidation reaction of the third step (1) of the method, the oxidant is CrO ₃ , the molar ratio of the compound of formula (VI) to the oxidant is 1:(4-8), preferably 1:6; the solvent is glacial acetic acid+water, the volume ratio (2～4):1, preferably 3:1.

The conditions of the silica gel column chromatography used in step (5) of method one, step (3) of method two and step (4) of method three are: eluting agent is dichloromethane:methanol, volume ratio 40:1～ 10:1, after the eluent solutions containing product components are combined, they are washed with 1mol/L dilute hydrochloric acid, dried with anhydrous Na ₂ SO ₄ , suction filtered, and concentrated.

3. Beneficial effect

The invention provides a brand new chiral skeleton of 5,5'-tetralone and a chiral phosphoric acid with the skeleton of 5,5'-tetralone. The invention also provides a method for efficiently preparing chiral phosphoric acid based on 5,5'-binetralone-6,6'-diol. The method has the advantages of inexpensive raw materials, short steps, mild reaction conditions, no racemization, simple operation and high yield, and is suitable for industrial large-scale synthesis. The prepared chiral phosphoric acid can be used as a catalyst for Mannich reaction, Biginelli reaction, Friedel-Crafts reaction, Diels-Alder reaction, transfer hydrogenation reaction and the like. For example, be applied to the transfer hydrogenation reaction of 2-phenylquinoline and Hantzsch ethyl ester: 0.2mol% catalyst consumption, benzene is made solvent, reacts 11 hours under room temperature, can obtain quantitative yield and enantiomeric excess of 98% ( ee); and under the same conditions, the phosphoric acid reaction is faster than that of the corresponding H ₈ -BINOL and BINOL skeleton, and the conversion rate increases up to 35% and 20%, respectively.

Description of drawings

Figure 1 is a single crystal X-ray diffraction pattern of (R)-7,7'-dibromo-5,5'-binethalone-6,6'-diol (3).

Fig. 2 is a single crystal X-ray diffraction pattern of (R)-7,7'-diphenyl-5,5'-tetralone-6,6'-diphenol-phosphoric acid (11).

Figure 3 is (R)-7,7'-bis[3,5-bis(trifluoromethyl)-phenyl]-5,5'-tetralone-6,6'-diphenol-phosphoric acid Single crystal X-ray diffraction pattern of (12).

Figure 4 is (R)-7,7'-bis(2,4,6-triisopropylphenyl)-5,5'-tetralone-6,6'-diphenol-phosphoric acid (13 ) single crystal X-ray diffraction pattern.

Detailed ways

The following examples help to understand the present invention, but do not limit the content of the present invention. The following description is only a preferred embodiment of the present invention, for those of ordinary skill in the art, without departing from the principle of the present invention, some improvements and modifications can also be made, and these improvements and modifications should also be considered Be the protection scope of the present invention. The reaction conditions in the examples apply equally to the other enantiomer not mentioned and to its racemate.

The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials and reagents used therein can be obtained from commercial sources unless otherwise specified.

Embodiment 1, the preparation of (R)-5,5'-tetralone-6,6'-diol (2)

The reaction equation is shown in the above formula, wherein, DDQ is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone;

Weigh (R)-H ₈ -BINOL (4.42g, 15.0mmol) into a 500mL single-necked bottle, add 100mL 1,4-dioxane and 5mLH ₂ O and stir to dissolve. DDQ (13.62 g, 60.0 mmol) was added under ice cooling. After reacting at 25°C for 4 hours, filter with suction, and wash the filter residue with 50 mL of 1,4-dioxane. Concentrate the filtrate, add 200 mL of ethyl acetate, and wash with saturated Na ₂ SO ₃ solution three times. The organic phase was dried over anhydrous Na ₂ SO ₄ , filtered with suction, concentrated, and directly sent to the next step. It can also be purified by silica gel column chromatography (petroleum ether: ethyl acetate, volume ratio 2:1 ~ 1:2) to obtain a white solid. Melting point 263～264℃; [α] _D ²⁰ ＝+129.2(c0.48, MeOH); IR (film) 3164, 2945, 1648, 1571, 1274, 1186cm ^-1 ; ¹ HNMR (400MHz, MeOD) δ7.98 (d,J=8.8Hz,2H),6.90(d,J=8.8Hz,2H),5.50(s,2H),2.67-2.53(m,6H),2.49-2.38(m,2H),2.09- 1.91 (m, 4H); ¹³ CNMR (100MHz, MeOD) δ199.0, 160.2, 146.7, 128.8, 125.1, 121.6, 113.8, 38.1, 26.8, 22.8; HRMS (ESI) Calcd for C ₂₀ H ₁₉ O ₄ (M+H): 323.1278; Found: 323.1278.

Example 2, the preparation of (R)-7,7'-dibromo-5,5'-tetralone-6,6'-diol (3)

In a water bath at 25°C, add 100mL of 1,4-dioxane to a 250mL single-necked bottle, add HBr (48%aq) (7.5mL, 66.0mmol) under stirring, and then add H ₂ O ₂ (35%aq ) (3.7mL, 42.9mmol), and the product from the previous step was added. After reacting for 1 hour, add a solution of 0.95g Na ₂ SO ₃ dissolved in 25 mL water, stir for half an hour, adjust the pH to 8-9 with 10% NaOH aqueous solution, and wash with ethyl acetate three times. Use 6mol/L dilute hydrochloric acid to acidify the aqueous phase to pH 1~2, extract with ethyl acetate, dry _over anhydrous _Na2SO4 , filter with suction, concentrate, and perform silica gel column chromatography (petroleum ether: ethyl acetate, volume ratio 3:1 ~3:2), 4.90 g of light yellow solid product was obtained, and the total yield of the two steps was 68%. Melting point 280～281℃; [α] _D ²⁰ ＝+83.0(c0.42, MeOH); IR (film) 3281, 2947, 1662, 1560, 1231, 1189cm ^-1 ; ¹ HNMR (400MHz, MeOD) δ8.23 (s,2H),2.59(t,J＝6.4Hz,4H),2.55-2.33(m,4H),2.10-1.95(m,4H); ¹³ CNMR(100MHz,MeOD)δ197.4,156.3,145.4,132.1 , 126.6, 122.6, 109.5, 37.8, 26.6, 22.5; HRMS (ESI) CalcdforC ₂₀ H ₁₇ Br ₂ O ₄ (M+H): 478.9488; Found: 478.9490. The single crystal X-ray diffraction pattern of compound (3) is shown in Attachment 1.

Example 3, the preparation of (R)-7,7'-diphenyl-5,5'-bitetralone-6,6'-diol (4)

The reaction equation is as shown in the above formula, wherein Ac is acetyl; Ph is phenyl; nBu is ⁿ -butyl; Ad is adamantyl; DME is ethylene glycol dimethyl ether;

Under argon protection, compound (R)-3 (5.0g, 10.46mmol), phenylboronic acid (4.46g, 36.61mmol), palladium acetate (0.0472g, 0.21mmol), bis(adamantyl ) n-butylphosphine (0.094g, 0.262mmol), 90mL ethylene glycol dimethyl ether and 45mL 1.0mol/L potassium carbonate solution. The reactor was placed in a 95°C oil bath and stirred. Stop heating after 11 hours, cool to room temperature, add 50 mL of saturated ammonium chloride solution, acidify to pH 3-4 with 1.6 mol/L dilute hydrochloric acid in ice bath, let stand for 2 hours, and filter with suction (obtain filtrate 1). The filter cake was dissolved in dichloromethane/methanol, dried over anhydrous Na ₂ SO ₄ , filtered with suction, concentrated to quick dryness, filtered with suction (to obtain filtrate 2), and washed with petroleum ether to obtain 4.08 g of a gray solid product. The filtrate 1 was extracted with dichloromethane, dried over anhydrous Na ₂ SO ₄ , filtered with suction, combined with the filtrate 2 and concentrated, followed by silica gel column chromatography (petroleum ether:ethyl acetate, volume ratio 4:1～2:1), and another One batch of product is 0.68g, and the total yield is 95%. Melting point 300～301℃; [α] _D ²⁰ ＝+36.5(c0.51, EtOAc); IR(film) 3296, 2945, 1664, 1582, 1233, 1181cm ^-1 ; ¹ HNMR(400MHz, DMSO-d ₆ ) δ9.03(s,2H),7.88(s,2H),7.56(d,J=7.2Hz,4H),7.46(t,J=7.2Hz,4H),7.36(t,J=7.6Hz,2H ),2.63-2.32(m,8H),2.04-1.88(m,4H); ¹³ CNMR(100MHz,DMSO-d ₆ )δ196.9,157.2,145.7,138.5,129.6,128.7,128.4,127.5,126.1,122.4, 38.5, 27.3, 23.0; HRMS (ESI) Calcd for C ₃₂ H ₂₇ O ₄ (M+H): 475.1904; Found: 475.1903.

Example 4, (R)-7,7'-bis[3,5-bis(trifluoromethyl)-phenyl]-5,5'-tetralone-6,6'-diphenol ( 5) Preparation

The reaction equation is shown in the above formula, wherein Ac is acetyl, nBu is ⁿ -butyl; Ad is adamantyl; DME is ethylene glycol dimethyl ether;

Under argon protection, compound (R)-3 (3.62g, 7.6mmol), 3,5-bis(trifluoromethyl)phenylboronic acid (5.88g, 22.8mmol), palladium acetate (0.0342 g, 0.152mmol), di(adamantyl) n-butylphosphine (0.0682g, 0.190mmol), 80mL ethylene glycol dimethyl ether and 40mL 1.0mol/L potassium carbonate solution. The reactor was placed in a 95°C oil bath and stirred. Stop heating after 9 hours, cool to room temperature, add 40mL saturated ammonium chloride solution, acidify to pH 3~4 with 3mol/L dilute hydrochloric acid in ice bath, extract with ethyl acetate, dry with anhydrous Na ₂ SO ₄ , filter with suction, and concentrate Silica gel column chromatography (petroleum ether: ethyl acetate, volume ratio 5:1-3:1), the product was light brown solid 5.11g, yield 90%. Melting point 189～190℃; [α] _D ²⁰ ＝+6.9(c0.32,THF); IR(film)3280,2944,1657,1559,1276,1125cm ^-1 ; ¹ HNMR(400MHz,MeOD)δ8.23 (s,4H),8.17(s,2H),7.96(s,2H),2.71-2.59(m,6H),2.59-2.49(m,2H),2.18-2.01(m,4H); ¹³ CNMR( 100MHz,MeOD)δ198.4,157.4,147.4,140.5,131.1(q,J _CF ＝32.9Hz),130.2,129.5,126.2,125.6,123.6(q,J _CF ＝270.2Hz),121.1,120.3,37.9,27.0, 22.6; HRMS (ESI) Calcd for C ₃₆ H ₂₃ F ₁₂ O ₄ (M+H): 747.1399; Found: 747.1381.

Example 5, (R)-7,7'-bis(2,4,6-triisopropylphenyl)-5,5'-tetralone-6,6'-dimethyl ether (7) preparation of

The reaction equation is as shown in the above formula, wherein, Me is a methyl group; ⁱ Pr is an isopropyl group; Ac is an acetyl group;

In a water bath, slowly add a solution of chromium trioxide (2.688g, 26.88mmol) in glacial acetic acid/water (10mL, volume ratio 3:1) dropwise to compound 6 (3.257g, 4.48mmol) in 25mL of glacial acetic acid suspension , dripped in 15 minutes. React at room temperature for 24 hours, add crushed ice, neutralize with 10% NaOH, extract with dichloromethane, wash with saturated NaHCO ₃ , dry with anhydrous Na ₂ SO ₄ , filter with suction, concentrate and perform silica gel column chromatography (petroleum ether: ethyl acetate, Volume ratio 19:1), 0.77 g of light yellow solid was obtained, yield 23%. Melting point 284～285℃; [α] _D ²⁰ ＝+2.45(c0.245, CH ₂ Cl ₂ ); IR (film) 2960, 1679, 1589, 1459, 1222 cm ^-1 ; ¹ HNMR (400MHz, CDCl ₃ ) δ7 .92(s,2H),7.05(s,2H),7.04(s,2H),3.17(s,6H),2.99-2.86(m,2H),2.75-2.59(m,10H),2.59-2.46 (m,2H),2.17-2.06(m,4H),1.30(d,J=7.2Hz,12H),1.19(d,J=6.8Hz,6H),1.14-1.06(m,18H); ¹³ CNMR (100MHz, CDCl ₃ )δ197.8, 159.8, 148.8, 146.8, 146.7, 143.9, 132.5, 131.6, 131.1, 129.1, 128.4, 121.1, 121.0, 59.5, 39.1, 34.5, 31.2, 31.0, 25.5, 24.6, 2 24.28, 23.6, 23.4, 23.3; HRMS (ESI) Calcd for C ₅₀ H ₆₇ O ₄ (M+H): 755.5034; Found: 755.5027.

Example 6, (R)-7,7'-bis(2,4,6-triisopropylphenyl)-5,5'-tetralone-6,6'-diol (8) preparation

The reaction equation is shown in the above formula, wherein Me is methyl; ⁱ Pr is isopropyl; Et is ethyl; DMF is N,N-dimethylformamide;

Compound 7 (0.755g, 1.0mmol), a mixture of NaSEt (0.504g, 6.0mmol) in 5mL DMF was reacted at 130°C for 10 hours. Cool to room temperature, quench with 2mL saturated NH ₄ Cl, acidify to pH 3-4 with 5% dilute hydrochloric acid, extract with ethyl acetate, wash the organic phase with saturated brine, dry with anhydrous Na ₂ SO ₄ , filter with suction, and concentrate on silica gel column Analysis (petroleum ether: ethyl acetate, volume ratio 10:1-7:1) gave 0.615 g of light yellow solid with a yield of 85%. Melting point 314～316℃; [α] _D ²⁰ ＝+11.9(c0.42, CH ₂ Cl ₂ ); IR(film) 3278,2958,1665,1598,1556,1228,1181cm ^-1 ; ¹ HNMR(400MHz, CDCl ₃ )δ7.94(s,2H),7.12(d,J=1.2Hz,2H),7.10(d,J=1.6Hz,2H),5.05(s,2H),2.99-2.87(m,2H ),2.72-2.52(m,12H),2.17-2.07(m,4H),1.30(d,J=6.8Hz,12H),1.16(d,J=6.8Hz,6H),1.11(d,J= 6.8Hz, 6H), 1.06(d, J＝6.8Hz, 6H), 0.98(d, J＝6.8Hz, 6H); ¹³ CNMR(100MHz, CDCl ₃ ) δ197.6, 155.6, 150.2, 148.6, 148.4, 145.1, 130.2, 128.2, 126.7, 125.6, 121.9, 121.8, 120.5, 39.0, 34.6, 30.9, 30.8, 27.3, 24.39, 24.36, 24.26, 24.22, 24.19, 24.0, 23.3; _HRMS (ESI) _CalcdforC 504 HM ₆₃ +H):727.4721; Found:727.4716.

Example 7, Preparation of (R)-7,7'-bistriphenylsilyl-5,5'-bistetralone-6,6'-diol (10)

Under argon protection, compound 9 (2.92g, 3.6mmol), DDQ (4.91g, 21.6mmol), FeCl _{2 ·} 4H ₂ O (0.146g, 0.73mmol), 1,2-dichloroethane were sequentially added to the reactor. alkanes (29 mL), THF (9 mL) and water (1.3 mL). The reactor was placed in a 30°C oil bath and stirred. Stop heating after 13 hours, cool to room temperature, add 40mL saturated NH ₄ Cl solution, NaHSO ₃ (0.5g), anhydrous MgSO ₄ Dry, suction filter, silica gel column chromatography after concentration (petroleum ether: ethyl acetate, volume ratio 9:1-4:1), the product obtained was 1.232 g of white solid, and the yield was 40%. Melting point 189-190°C; [α] _D ²⁰ =+42.4 (c0.33, CH ₂ Cl ₂ ); IR (film) 3276, 3068, 2945, 1675, 1555, 1428, 1232, 1108cm ^-1 ; ¹ HNMR ( 400MHz, CDCl ₃ )δ8.16(s,2H),7.60-7.53(m,12H),7.47-7.41(m,6H),7.39-7.32(m,12H),5.47(s,2H),2.62- 2.45(m,8H),2.10-1.96(m,4H); ¹³ CNMR(100MHz,CDCl ₃ )δ196.5,162.8,148.3,140.0,136.4,133.3,130.2,128.3,127.3,119.9,118.4,38.7,27.6, 23.0; HRMS (ESI) Calcd for C ₅₆ H ₄₇ O ₄ Si ₂ (M+H): 839.3007; Found: 839.3000.

Example 8, Preparation of (R)-7,7'-diphenyl-5,5'-binethalone-6,6'-diphenol-phosphoric acid (11)

The reaction equation is as shown in the above formula, wherein, Ph is phenyl; Py is pyridine;

Under argon protection, phosphorus oxychloride (1.94 g, 12.63 mmol) was slowly added dropwise to a solution of 4 (2.0 g, 4.21 mmol) in 12 mL of pyridine, and the reaction was refluxed for 12 hours. After cooling to room temperature, water (12 mL) was slowly added dropwise, and the reaction was refluxed for 5 hours. Cool to room temperature, add 80mL3mol/L dilute hydrochloric acid, extract with dichloromethane, dry _over anhydrous _Na2SO4 , filter with suction, concentrate, and perform silica gel column chromatography (dichloromethane:methanol, volume ratio 19:1～13:1) , and the eluent solutions containing the product components were combined, washed with 200 mL of 1mol/L dilute hydrochloric acid, dried over anhydrous Na ₂ SO ₄ , filtered with suction, and concentrated to obtain 1.65 g of a white solid with a yield of 73%. Melting point 289～291℃; [α] _D ²⁰ ＝-86.6(c0.33, THF); IR(film) 3385, 2938, 1678, 1259, 1230, 1100cm ^-1 ; ¹ HNMR(400MHz, DMSO-d ₆ ) δ8.03(s, 2H), 7.74(d, J=7.2Hz, 4H), 7.46(t, J=7.4Hz, 4H), 7.39(t, J=7.2Hz, 2H), 3.04-2.88(m ,2H),2.80-2.58(m,4H),2.56-2.39(m,2H),2.17-2.03(m,2H),2.00-1.86(m,2H); ¹³ CNMR(100MHz,DMSO-d ₆ ) δ197.1, 150.7, 150.6, 145.1, 136.8, 132.9, 132.8, 129.9, 129.7, 128.7, 128.1, 127.6, 38.7, 27.8, 23.3; ³¹ PNMR (162MHz, DMSO-d ₆ ) δ-2.39; HRMS (ESI) _CalcdforC H ₂₆ O ₆ P(M+H):537.1462; Found:537.1456. The single crystal X-ray diffraction pattern of compound (11) is shown in Figure 2.

Example 9, (R)-7,7'-bis[3,5-bis(trifluoromethyl)-phenyl]-5,5'-tetralone-6,6'-diphenol- Preparation of phosphoric acid (12)

The reaction equation is as shown in the above formula, wherein, Py is pyridine;

Under the protection of argon, phosphorus oxychloride (0.1027g, 0.67mmol) was slowly added dropwise to a solution of 5 (0.25g, 0.335mmol) in 1.0mL of pyridine, reacted at 70°C for 3 hours, cooled to room temperature, and slowly added dropwise with water (0.5 mL), react at 70°C for 2 hours. Cool to room temperature, add 15 mL of dichloromethane and 15 mL of 1mol/L dilute hydrochloric acid successively, extract the aqueous phase with dichloromethane, combine the organic phases, dry _over anhydrous _Na2SO4 , filter with suction, concentrate, and perform silica gel column chromatography (dichloromethane : Methanol, volume ratio 20:1～10:1), after the eluent solutions containing product components were combined, washed with 50mL1mol/L dilute hydrochloric acid, dried _over anhydrous _Na2SO4 , suction filtered, and concentrated to give 0.2251g of white solid , yield 83%. Melting point>320℃; [α] _D ²⁰ ＝-16.7(c0.39,THF); IR(film)3441,2948,1683,1279,1132cm ^-1 ; ¹ HNMR(400MHz,DMSO-d ₆ )δ8.66 (s,4H),8.12(s,2H),8.09(s,2H),3.05-2.92(m,2H),2.81-2.58(m,4H),2.54-2.42(m,2H),2.17-2.02 (m,2H),1.98-1.85(m,2H); ¹³ CNMR(100MHz,DMSO-d ₆ )δ197.0,152.6(d,J _CP ＝9Hz),146.2,139.9,131.2,130.5(q,J _CF ＝ 33Hz), 130.0, 129.8, 129.3, 128.2, 123.9 (q, J _CF = 271Hz), 121.5, 38.7, 27.9, 23.3; ³¹ PNMR (162MHz, DMSO-d ₆ ) δ-0.23; HRMS (ESI) CalcdforC ₃₆ H ₂₂ F ₁₂ O ₆ P(M+H): 809.0957; Found: 809.0948. The single crystal X-ray diffraction pattern of compound (12) is shown in Figure 3.

Example 10, (R)-7,7'-bis(2,4,6-triisopropylphenyl)-5,5'-tetralone-6,6'-diphenol-phosphoric acid ( 13) Preparation

The reaction equation is as shown in the above formula, wherein, ⁱ Pr is isopropyl; Py is pyridine;

Under the protection of argon, slowly drop phosphorus oxychloride (0.382g, 2.49mmol) in 3.0mL pyridine solution of 8 (0.60g, 0.83mmol), cool to room temperature after reflux reaction for 5 hours, slowly add water (3.0mL ), reflux reaction for 3 hours. Cool to room temperature, add 20mL 3mol/L dilute hydrochloric acid, extract with dichloromethane, dry over anhydrous Na ₂ SO ₄ , filter with suction, concentrate, and perform silica gel column chromatography (dichloromethane:methanol, volume ratio 40:1～30:1) , and the eluent solutions containing the product components were combined, washed with 100 mL of 1 mol/L dilute hydrochloric acid, dried over anhydrous Na ₂ SO ₄ , filtered with suction, and concentrated to obtain 0.59 g of off-white solid with a yield of 90%. Melting point 303～304℃; [α] _D ²⁰ ＝-113.5(c0.37, THF); IR(film) 3439, 2959, 1690, 1460, 1362, 1222cm ^-1 ; ¹ HNMR(400MHz, DMSO-d ₆ ) δ7.78(s,2H),7.11(d,J=1.2Hz,2H),7.04(d,J=1.2Hz,2H),3.02-2.85(m,4H),2.78-2.62(m,6H) ,2.54-2.38(m,4H),2.22-2.09(m,2H),2.09-1.97(m,2H),1.25(d,J＝6.8Hz,12H),1.18-1.05(m,18H),0.86 (d, J = 6.8Hz, 6H); ¹³ CNMR (100MHz, DMSO-d ₆ ) δ197.0, 151.1 (d, J _CP = 9Hz), 148.5, 147.6, 146.6, 144.8, 131.4, 130.9 (d, J _CP = 6Hz),130.9,129.7,126.8,121.4,120.5,38.6,34.0,31.0,30.7,27.4,26.6,24.9,24.5,24.4,23.7,23.3,23.2; ³¹ PNMR(162MHz,DMSO-d ₆ )δ-2.71 ; HRMS (ESI) CalcdforC ₅₀ H ₆₂ O ₆ P (M+H): 789.4279; Found: 789.4265. The single crystal X-ray diffraction pattern of compound (13) is shown in accompanying drawing 4.

Example 11, Preparation of (R)-7,7'-triphenylsilyl-5,5'-tetralone-6,6'-diphenol-phosphoric acid (14)

Under argon protection, phosphorus oxychloride (0.2 mL, 16.56 mmol) was slowly added dropwise to a solution of compound 10 (0.616 g, 0.734 mmol) in 3 mL of pyridine, and the reaction was refluxed for 12 hours. After cooling to room temperature, water (3 mL) was slowly added dropwise, and the reaction was refluxed for 5 hours. Cool to room temperature, add 20 mL of 3mol/L dilute hydrochloric acid, extract with dichloromethane, dry over anhydrous Na ₂ SO ₄ , filter with suction, concentrate, and perform silica gel column chromatography (dichloromethane:methanol, volume ratio 19:1-13:1) , and eluent solutions containing product components were combined, washed with 50 mL of 1mol/L dilute hydrochloric acid, dried over anhydrous Na ₂ SO ₄ , filtered with suction, and concentrated to obtain 0.38 g of a white solid with a yield of 54%. Melting point 227-228°C; [α] _D ²⁰ =-155.0 (c0.305, CH ₂ Cl ₂ ); IR (film) 3376, 2925, 1685, 1545, 1428, 1234, 1108cm ^-1 ; ¹ HNMR (400MHz, DMSO-d ₆ )δ8.03(s,2H),7.52-7.46(m,12H),7.45-7.39(m,6H),7.39-7.32(m,12H),3.00-2.86(m,2H), 2.73-2.53(m,4H),2.48-2.36(m,2H),2.14-2.01(m,2H),1.98-1.85(m,2H); ¹³ CNMR(100MHz,DMSO-d ₆ )δ197.1,158.8, ₅ ^_ _{_} H ₄₅ NaO ₆ PSi ₂ (M+Na): 923.2384; Found: 923.2386.

Claims (10)

1. A 5,5'-tetralone-6,6'-dioxygen compound, characterized in that: it has the following structural formula: Wherein, R is selected from one of H, Cl, Br, I, C6-C19 alkyl, substituted silicon, substituted aryl or conjugated aryl, and the conjugated aryl is naphthyl, One of anthracenyl and phenanthrenyl; R1 is selected from ^one of H, Ac, Boc, Bz, MOM, C1～C8 alkyl; the 5,5'-tetralone-6, The 6'-dioxygen compound is one of R type, S type or racemate. 2. A 5,5'-tetralone-6,6'-diphenol-phosphoric acid, characterized in that: it has the following structural formula: Wherein, R is selected from one of H, Cl, Br, I, C6-C19 alkyl, substituted silicon, substituted phenyl or conjugated aryl, and the conjugated aryl is naphthyl, One of anthracenyl and phenanthrenyl; the 5,5'-binatelone-6,6'-diphenol-phosphoric acid is one of R type, S type or racemate. 3. the method for preparing 5,5'-tetralone-6,6'-diphenol-phosphoric acid, characterized in that: Using Method 1, the steps are: (1) H ₈ -BINOL is oxidized in an organic solvent (or containing water) through an appropriate catalyst, appropriate temperature and time to obtain 5,5'-tetralone-6 represented by formula (II), 6'-diphenol; (2) 5,5'-tetralone-6,6'-diol represented by formula (II) undergoes a halogenation reaction to obtain 7,7'-dihalo-5,5 represented by formula (III) '-tetralone-6,6'-diol; (3) 7,7'-dihalo-5,5'-tetralone-6,6'-diol represented by formula (III), undergoes a coupling reaction to obtain 7 represented by formula (IV), 7'-disubstituted-5,5'-tetralone-6,6'-diol; (4) 7,7'-disubstituted-5,5'-tetralone-6,6'-diphenol shown in formula (IV), after reacting with phosphorus oxychloride in alkaline conditions, then After hydrolysis, the 7,7'-disubstituted-5,5'-binethalone-6,6'-diphenol-phosphoric acid represented by the formula (I) is obtained; (5) Purify the compound of formula (I) prepared by silica gel column chromatography; Or use method 2, the steps are: (1) 3,3'-disubstituted-H ₈ -BINOL represented by formula (V), in an organic solvent (or containing water), through an oxidation reaction with a suitable catalyst, a suitable temperature and time, to obtain the formula (IV) Represents 7,7'-disubstituted-5,5'-tetralone-6,6'-diol; (2) 7,7'-disubstituted-5,5'-tetralone-6,6'-diphenol shown in formula (IV), after reacting with phosphorus oxychloride in alkaline conditions, then After hydrolysis, the 7,7'-disubstituted-5,5'-binethalone-6,6'-diphenol-phosphoric acid represented by the formula (I) is obtained; (3) Purify the compound of formula (I) prepared by silica gel column chromatography; Or use method three, the steps are: (1) 3,3'-disubstituted-H ₈ -binaphthol-2,2'-dioxygen compound represented by formula (VI), in organic solvent (or containing water), after proper catalyst action, proper temperature and Oxidation reaction of time to obtain 7,7'-disubstituted-5,5'-binethalone-6,6'-dioxy compound shown in formula (VII); (2) The 7,7'-disubstituted-5,5'-tetralone-6,6'-dioxy compound shown in (VII) is deprotected to obtain the 7,7 shown in the formula (IV). '-Disubstituted-5,5'-tetralone-6,6'-diol; (3) 7,7'-disubstituted-5,5'-tetralone-6,6'-diphenol shown in formula (IV), after reacting with phosphorus oxychloride in alkaline conditions, then After hydrolysis, the 7,7'-disubstituted-5,5'-binethalone-6,6'-diphenol-phosphoric acid represented by the formula (I) is obtained; (4) Purify the prepared compound of formula (I) by silica gel column chromatography. 4. the method for preparing 5,5'-tetralone-6,6'-diphenol-phosphoric acid as claimed in claim 3, is characterized in that: in method one step, X is Cl, Br, in I One; R is a substituted phenyl group or a conjugated aryl group, and the conjugated aryl group is one of naphthyl, anthracenyl, and phenanthrenyl; in the second step of the method, R is a substituted silicon group; the third step of the method R1 is ^one of Ac, Boc, Bz, MOM, C1～C8 alkyl; R is a substituted phenyl group. 5. the method for preparing 5,5'-tetralone-6,6'-diphenol-phosphoric acid as claimed in claim 4, is characterized in that: in the method one route, X is Br; R is phenyl and 3,5-bis(trifluoromethyl)phenyl; R in the second route of method is triphenylsilyl; R in the third route ^of method is Me; R is 2,4,6-triisopropylphenyl. 6. the method for preparing 5,5'-tetralone-6,6'-diphenol-phosphoric acid as claimed in claim 3, is characterized in that: the oxidizing agent used in the oxidation reaction of method one step (1) 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the molar ratio of H ₈ -BINOL and oxidizing agent is 1:(4～6); In the oxidation reaction of the second step (1) of the method, the oxidant is DDQ, and a ferrous chloride catalyst is added, and the molar ratio of the compound of formula (V), the oxidant and the catalyst is 1:(4～6):(0.05～0.2); In the oxidation reaction of method three steps (1), the oxidant is CrO ₃ , and the molar ratio of the compound of formula (VI) to the oxidant is 1:(4-8); the solvent is glacial acetic acid+water, and the volume ratio is (2-4 ):1. 7. the method for preparing 5,5'-tetralone-6,6'-diphenol-phosphoric acid as claimed in claim 6, is characterized in that: the oxidizing agent used in the oxidation reaction of method one step (1) 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the molar ratio of H ₈ -BINOL and oxidizing agent is 1:4; In the oxidation reaction of method two steps (1), the oxidizing agent is DDQ, and a ferrous chloride catalyst is added, and the molar ratio of the compound of formula (V), the oxidizing agent and the catalyst is 3.6:21.6:0.73; In the oxidation reaction of the third step (1) of the method, the oxidant is CrO ₃ , the molar ratio of the compound of formula (VI) to the oxidant is 1:6; the solvent is glacial acetic acid+water, and the volume ratio is 3:1. 8. The method for preparing 5,5'-tetralone-6,6'-diphenol-phosphoric acid as claimed in claim 3, characterized in that: the coupling reaction conditions of method one step (3) are: The catalyst is palladium acetate+1,1'-bis(diphenylphosphine)ferrocene (dppf), palladium acetate+bis(adamantyl)n-butylphosphine, palladium acetate+2-dicyclohexylphosphine-2' , 6'-dimethoxybiphenyl (Sphos), bis(triphenylphosphine) nickel chloride, bis[1,3-bis(diphenylphosphine) propane] nickel chloride, cuprous iodide One, the base is one of potassium carbonate, potassium phosphate, cesium carbonate, the solvent is one of ether, tetrahydrofuran, toluene + ethanol, ethylene glycol dimethyl ether + water, 1,4-dioxane + water . 9. The method for preparing 5,5'-tetralone-6,6'-diphenol-phosphoric acid as claimed in claim 8, characterized in that: the coupling reaction conditions of method one step (3) are: The catalyst is palladium acetate + di(adamantyl) n-butylphosphine, the base is potassium carbonate, and the solvent is ethylene glycol dimethyl ether + water. 10. the method for preparing 5,5'-tetralone-6,6'-diphenol-phosphoric acid as claimed in claim 3, is characterized in that: the step (5) of method one, the step of method two ( 3), the conditions of silica gel column chromatography used in step (4) of method three are: the eluent is dichloromethane+methanol, the volume ratio is 40:1～10:1, and the eluent solution containing product components After combining, they were successively washed with 1 mol/L dilute hydrochloric acid, dried over anhydrous Na ₂ SO ₄ , suction filtered, and concentrated.