Optically active diphenol with both central chirality and axial chirality as well as synthesis method and application of optically active diphenol

Abstract

The invention relates to optically active diphenol with both central chirality and axial chirality as well as a synthesis method and application of the optically active diphenol. The structural formula of the optically active diphenol is as follows: # imgabs0 #, wherein Ar1 is an aryl compound or a heteroaryl compound with different substituent groups, Ar3 is an aryl compound with different substituent groups, Ar2 is an aryl compound or a heteroaryl compound with different substituent groups, and Ar4 is halogen or hydrogen. The invention focuses on an enantioselective synthesis method for constructing a diphenol compound NAPOLs with rigid conformation. The synthesis method comprises the following steps: catalyzing 1-aryl ethynyl-2-naphthol and a derivative thereof and 8-aryl hydroxymethyl-2-naphthol and a derivative thereof through chiral phosphoric acid to synthesize an optically active NAPOLs diphenol ligand with axial chirality and central chirality. The compound has the characteristics of central chirality and axial chirality, and is expected to provide a new idea for the field of asymmetric synthesis.

Description

Technical Field

[0001] The present invention relates to the technical field of preparation of optically active materials, in particular to an optically active diphenol having both central chirality and axial chirality, and a synthesis method and application thereof. Background Art

[0002] Chiral elements are ubiquitous in natural products and pharmaceutical molecules. With the continuous advancement of organic small molecule catalysis, researchers can manipulate the absolute configuration of central or axial chirality through "chiral matching" or "chiral mismatching" strategies, thereby controlling the stereoselectivity of compounds. Furthermore, precisely regulating the steric and electronic effects of chiral groups can create specific chiral environments at the molecular level, further enhancing reaction precision.

[0003] Despite significant progress in the construction of axially chiral diphenol ligands and catalysts, currently available chiral diphenol (alcohol) ligands are limited to constructing a single chiral center (central or axial chirality). Molecular scaffolds with multiple chiral features, with their unique chiral properties and advantageous conformations, play an important role in chiral catalysts and bioactive molecules, showing broad application prospects. However, the asymmetric synthesis of such molecular scaffolds through catalytic strategies is still in its early stages of exploration, and related reports are extremely limited. In particular, achieving high enantioselectivity when constructing compounds with both central and axial chirality is a significant challenge. Summary of the Invention

[0004] To address the above technical problems, the present invention provides an optically active diphenol with both central and axial chirality, as well as a synthesis method and application thereof. This invention focuses on constructing an enantioselective synthesis of conformationally rigid diphenol compounds, NAPOLs. These compounds possess both central and axial chirality and are expected to provide new insights into asymmetric synthesis.

[0005] The first object of the present invention is to provide an optically active diphenol having both central chirality and axial chirality, the general structural formula of the optically active diphenol is as follows:

[0006] Among them, Ar 1 is an aromatic compound or heteroaryl compound with different substituents, Ar 3 Aryl compounds with different substituents, Ar 2 is an aromatic compound or heteroaryl compound with different substituents, Ar 4 is halogen or hydrogen, the thick line on the benzene ring and Ar 2 The thick and dashed lines in the wedge shape can represent the absolute configuration of the compound, namely the axial chirality and the central chirality.

[0007] In some embodiments of the present invention, the Ar 1C6H5, 4-MeC6H4, 4-OMeC6H4, 4- n PrC6H4、4- t One or more of BuC6H4, 4-ClC6H4, 4-FC6H4, 4-PhC6H4, 2-MeC6H4, 2-thiophenyl, Naphthyl and 2,4,6-triMeC6H2.

[0008] The optically active diphenol having both central chirality and axial chirality according to claim 1, wherein the Ar 2 C6H5, 4-MeC6H4, 4-OMeC6H4, 4-SMeC6H4, 4- t One or more of BuC6H4, 4-PhC6H4, 4-CF3C6H4, 4-ClC6H4, 3-CF3C6H4, 3-ClC6H4, 2-MeC6H4, 2-OMeC6H4, and 2-thiophenyl.

[0009] In some embodiments of the present invention, the Ar 3 C6H5, 4- t One or more of BuC6H4, 4-PhC6H4, Naphthyl, 3,5-diCF3C6H3; the Ar 4 Halogen includes F, Cl, Br or I.

[0010] In some embodiments of the present invention, the optically active diphenol comprises any one of the following structures:

[0011]

[0012]

[0013] The second object of the present invention is to provide a method for preparing the optically active diphenol having both central chirality and axial chirality, comprising the following steps:

[0014]

[0015] Under an inert atmosphere, 1-arylethynyl-2-naphthol derivatives were 8-Arylhydroxymethyl-2-naphthol derivatives The product is mixed with a chiral phosphoric acid catalyst, and a molecular sieve additive and a reaction solvent are added, and heated for reaction to obtain the optically active diphenol.

[0016] In some embodiments of the present invention, the 1-arylethynyl-2-naphthol derivative 8-Arylhydroxymethyl-2-naphthol derivatives The ratio of the amount of substance is (1~2):(1~2);

[0017] The heating reaction temperature is 25-70°C and the time is 4-10 hours.

[0018] In some embodiments of the present invention, the chiral phosphoric acid catalyst comprises one or more of the following structures:

[0019]

[0020] One or more of;

[0021] Among them, R 1 is one or more of H, 2-naphthyl, 9-anthryl, 4-PhC6H4, TMS, 4,6-dihydropyren-1-yl, and 3,4,5-triFC6H2;

[0022] R 2 One or more of 4-tBuC6H4, 4-naphthylC6H4, 2,4,6-triipr-C6H2, 4-CF3C6H4, and 3,5-diCF3C6H3;

[0023] R 3 is H or 4-PhC6H4;

[0024] R 4 One or more of 4-CF3C6H4, 4-NO2C6H4, 3,5-diClC6H3, 3,5-diCF3C6H3, 4-PhC6H4, 2-naphthyl, 3,5-diCH3C6H3, 3,5-ditBuC6H3, SiPh3, 3,5-PhC6H3, and 3,5-di(3,5-diCF3C6H3)C6H3;

[0025] R 5 is one or more of phenyl, 2-naphthyl, 9-anthryl, 4-ClC6H4, and 3,5-diClC6H3;

[0026] Specifically:

[0027] C1:R 1 =H; C2:R 1 =2-naphthyl; C3:R 1 =9-anthryl;

[0028] C4:R 1 =4-PhC6H4; C5:R1 =TMS;C6:R 1 =4,6-dihydropyren-1-yl;C7:R 1 =

[0029] 3,4,5-triFC6H2;

[0030] C8:R 2 =4-tBuC6H4;C9:R 2 =4-naphthylC6H4;C10:R 2

[0031] =2,4,6-triipr-C6H2;C11:R 2 =4-CF3C6H4;C12:R 2 =3,5-diCF3C6H3;

[0032] C13:R 3 =H;C14:R 3 =4-PhC6H4;

[0033] C15:R 4 =4-CF3C6H4;C16:R 4 =4-NO2C6H4;C17:R 4 =

[0034] 3,5-diClC6H3;;C18:R 4 =3,5-diCF3C6H3;C19:R 4 =4-PhC6H4;C20:R 4 =2-naphthyl;C21:R 4 =3,5-diCH3C6H3;C22:R 4 =3,5-ditBuC6H3;C23:R 4 =SiPh3;C24:R 4 =3,5-PhC6H3;C25:R 4 =3,5-di(3,5-diCF3C6H3)C6H3;

[0035] C26:R 5 =phenyl;C27:R 5 =2-naphthyl;C28:R 5 =

[0036] 9-anthryl;C29:R5 =4-ClC6H4; C30:R 5 =3,5-diClC6H3.

[0037] In some embodiments of the present invention, the additive is selected from MS, MS and One or more of MS; further, preferably The present invention can effectively absorb water by adding molecular sieve additives, thereby ensuring good control of the water content in the system.

[0038] The reaction solvent is one or more of CH2Cl2, CHCl3, CCl4, DCE, Toluene, PhCF3, PhCl, CH3CN and THF; further, CCl4 is preferred.

[0039] The inert gas of the inert atmosphere is selected from nitrogen and / or argon.

[0040] The third object of the present invention is to provide the use of the optically active diphenol having both central chirality and axial chirality in catalyzing the petasis reaction of vinyl borate esters.

[0041] The above technical solution of the present invention has the following advantages over the prior art:

[0042] The synthesis method provided by the present invention uses 1-arylethynyl-2-naphthol as a nucleophile to attack the 8-methylene-2-naphthoquinone intermediate generated in situ from 8-hydroxymethyl-2-naphthol under the catalysis of chiral phosphoric acid, yielding α-alkenyl-β-naphthone. The α-alkenyl-β-naphthone then undergoes an intramolecular Friedel-Crafts reaction, ultimately synthesizing optically active NAPOLs diphenol ligands containing both axial and central chirality with a yield of up to 96%, 97% enantioselectivity, and >20:1 diastereoselectivity. This method has the advantages of high atom economy, mild conditions, and a wide substrate compatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] In order to make the content of the present invention more clearly understood, the present invention is further described in detail below based on specific embodiments of the present invention in conjunction with the accompanying drawings, wherein:

[0044] Figure 1 This is the H NMR spectrum of compound 3a obtained in Example 1 of the present invention.

[0045] Figure 2 This is the C NMR spectrum of compound 3a obtained in Example 1 of the present invention.

[0046] Figure 3This is a high performance liquid chromatogram of the racemic compound 3a obtained in Example 1 of the present invention.

[0047] Figure 4 This is the high performance liquid chromatogram of compound 3a obtained in Example 1 of the present invention.

[0048] Figure 5 This is the process for screening chiral phosphoric acid catalysts in Example 1 of the present invention. DETAILED DESCRIPTION

[0049] The present invention will be further described below with reference to the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it. However, the embodiments are not intended to limit the present invention.

[0050] The data given in the following examples include specific operation and reaction conditions and products, and the purity of the products was identified by nuclear magnetic resonance. The reagents described in the present invention were all commercially available analytical grade reagents.

[0051] 1-Arylethynyl-2-naphthol derivatives used in Examples 1 to 30 of the present invention Includes one or more of the following structures:

[0052]

[0053] 8-Arylhydroxymethyl-2-naphthol derivatives used Includes one or more of the following structures:

[0054]

[0055] Example 1

[0056] This example investigates an asymmetric catalytic reaction using 1-arylethynyl-2-naphthol and 8-arylhydroxymethyl-2-naphthol as template substrates. The effects of varying chiral phosphoric acid catalysts, reaction solvents, additives, reaction temperature, reaction time, and the ratio of compound 1a to 2a were investigated.

[0057] (1) Screening of chiral aldehyde catalysts: The results are shown in Table 1.

[0058] Table 1

[0059]

[0060]

[0061] It should be further explained that the ee value of the present invention only retains the whole decimal place.

[0062] The results in Table 1 show that most of the chiral phosphoric acids listed above can yield product 3a. C25 exhibits the best enantioselectivity, yielding the desired product with 92% ee. Therefore, C25 is the preferred chiral phosphoric acid catalyst.

[0063] (2) Screening of solvents: The results are shown in Table 2.

[0064]

[0065] Table 2

[0066]

[0067] The results in Table 2 show that product 3a can be obtained using the above reaction solvents. Considering the comprehensive consideration of bisecting enantioselectivity and enantioselectivity, CCl4 is preferred.

[0068] (3) Screening of additives. The results are shown in Table 3.

[0069] Table 3

[0070]

[0071] Add 100 mg to the system When MS molecular sieves were used, the reaction yield, diastereoselectivity, and enantioselectivity of 3a were maintained, while the enantioselectivity of 3a' was significantly improved. MS.

[0072] (4) Investigation of reaction temperature. The results are shown in Table 4.

[0073] Table 4

[0074]

[0075] Temperature significantly affects the yield, selectivity, and reaction rate of this reaction. Low temperatures are detrimental to the reaction. At 0°C, the reaction barely occurs. As the temperature rises to 70°C, the yield rises to 77%, while stereoselectivity is well maintained. Therefore, a reaction temperature of 70°C is preferred.

[0076] (5) Investigation of reaction time. The results are shown in Table 5.

[0077] Table 5

[0078]

[0079] With appropriate extension of reaction time, the dr value gradually increases. After 8 hours at 70°C, the dr value reaches >20:1 while maintaining enantioselectivity. Considering both yield and enantioselectivity, the optimal reaction time is 6 hours.

[0080] (6) Investigation of the reactant feed ratio. The results are shown in Table 6.

[0081] Table 6

[0082]

[0083]

[0084] Experimental results show that when the equivalent amount of 2a in the reaction system is higher than that of 1a, the reaction yield, diastereoselectivity, and enantioselectivity do not show significant changes. However, when the equivalent amount of 2a is lower than that of 1a, the reaction results show: the yield is greatly improved, which may be due to the increased driving force of the reaction when the excess amount of 1a is high; the diastereoselectivity is significantly reduced to 1:1, and the enantioselectivity of 3a' is significantly reduced. Therefore, a 1a:2a feed ratio of 1:1.5 is preferred.

[0085] In summary, the above experimental exploration process obtained the optimal parameters for the synthesis of 3a. The specific experimental process includes: taking chiral phosphoric acid catalyst, 1-arylethynyl-2-naphthol 1a, 8-arylhydroxymethyl-2-naphthol 2a, In a dry reaction tube, the reaction system was evacuated three times and then purged with argon. CCl4 (2 mL) was added. The reaction was allowed to proceed at 70°C. TLC was monitored. After the reaction was complete, the solid was removed by filtration through celite. The solvent was concentrated under reduced pressure. The reaction yield and diastereoselectivity were determined by proton nuclear magnetic resonance spectroscopy using dibromomethane as an internal standard. The corresponding product was then obtained by column chromatography.

[0086] The data characterization of 3a is as follows: (R)-3-(2-hydroxynaphthalen-1-yl)-1,2-diphenyl-1H-phenalen-4-ol

[0087] 1) Yellow oily liquid (yield 64%);

[0088] 2) R f =0.3 (petroleum ether / ethyl acetate=5:1);

[0089] 3) The enantiomeric excess was determined to be 91% by HPLC analysis (n-hexane / isopropanol = 90 / 10, flow rate 1 mL / min, T = 25°C); UV 254 nm, t R (minor)23.409min;t R(major)33.160min;

[0090] 4)[α]25D=-105.6°(c=0.1, EtOH);

[0091] 5) 1 H NMR (400MHz, CDCl3) δ7.68-7.59(m,5H),7.35-7.20(m,9H),6.96(d,J=8.9Hz,1H),6.86(t,J=8 .9Hz,2H),6.79(t,J=7.6Hz,2H),6.62(d,J=7.3Hz,2H),5.78(s,1H),5.62(s,1H),5.25(s,1H).

[0092] 6) 13 C NMR (101MHz, CDCl3, ppm) δ152.3,151.0,146.4,145.3,140.0,136.2,132.9,131.5,130.6,129.3,129.1,128.8,128.5,12 8.3,127.6,127.4,127.33,127.28,127.14,127.06,126.5,124.6,124.4,124.3,123.3,120.9,117.3,116.9,111.7,54.5.

[0093] 7) The HPLC chromatogram of racemic compound 3a is as follows Figure 3 As shown;

[0094] 8) The HPLC chromatogram of chiral compound 3a is as follows Figure 4 shown.

[0095] 9)(ESI) calcd. C 35 H 23 O2,[MH] - 475.1704, actual value 475.1694.

[0096] Examples 2 to 30

[0097] In this example, the optimal parameters in Example 1 were used to synthesize a series of chiral NAPOLs diphenol compounds, and the universality of the synthesis method was verified. The results of the obtained series of chiral NAPOLs diphenol compounds are shown in Table 7.

[0098] The specific operation is as follows: referring to the experimental steps for synthesizing 3a, the reaction is carried out according to the raw materials in Table 7:

[0099] Take chiral phosphoric acid catalyst, 1-aryl ethynyl-2-naphthol derivatives (1a-1q), 8-aryl hydroxymethyl-2-naphthol derivatives (2a-2n), In a dry reaction tube, the reaction system was evacuated three times and then purged with argon. CCl₄ (2 mL) was added and the reaction was allowed to proceed at 70°C. After completion of the reaction, solids were removed by filtration through celite. The solvent was concentrated under reduced pressure. The diastereoselectivity of the reaction was determined by proton nuclear magnetic resonance spectroscopy using dibromomethane as an internal standard. The corresponding products 3a-3da were then obtained by column chromatography.

[0100] Table 7

[0101]

[0102]

[0103]

[0104]

[0105]

[0106]

[0107]

[0108]

[0109] Note: The NAPOLs diphenol compounds in Table 7 were all identified by NMR.

[0110] The NMR data of compounds 3b-3da are shown below:

[0111] 3b: 1 H NMR (400MHz, CDCl3, ppm) δ7.78-7.54(m,5H),7.39-7.16(m,10H),7.00(d,J=9.0Hz,1H),6.84(d,J=8.9 Hz,1H),6.61(d,J=7.9Hz,2H),6.55-6.48(m,2H),5.75(s,1H),5.53(s,1H),5.22(s,1H),2.05(s,3H). 13C NMR(101MHz,CDCl3,ppm)δ152.2,150.8,146.5,145.3,137.0,136.6,136.3,133.0,131.3,130.4,129.3,129.1,128.8,128.4,128.3,128.0,127.6,127.2,127.13,127.07,127.0,126.3,124.5,124.4,124.3,123.2,120.8,117.4,117.0,111.8,54.7,21.0.

[0112] 3c: 1 H NMR(400MHz,CDCl3,ppm)δ7.72-7.57(m,5H),7.38-7.28(m,2H),7.29-7.20(m,3H),7.22-7.10(m,3H),7.07-6.98(m,3H),6.89(d,J=9.0Hz,1H),6.85-6.74(m,2H),6.58(ddd,J=8.9,6.5,2.5Hz,1H),6.32(d,J=7.1Hz,1H),5.72(s,1H),5.65(s,1H),5.14(s,1H),2.23(s,3H). 13 C NMR(101MHz,CDCl3,ppm)δ152.3,151.1,146.6,146.1,138.3,135.7,134.3,131.8,131.3,130.5,129.7,129.1,128.93,128.91,128.88,128.2,127.5,127.3,127.00,126.95,126.9,126.6,124.7,124.6,124.3,124.0,122.9,121.0,117.1,116.9,111.5,54.3,20.0.

[0113] 3d: 1H NMR(400MHz,CDCl3,ppm)δ7.70-7.55(m,5H),7.34(t,J=7.6Hz,1H),7.28-7.23(m,2H),7.23-7.15(m,2H),7.12(dd,J=5.0,1.9Hz,3H),7.04(d,J=8.9Hz,3H),6.96-6.89(m,3H),6.46(s,1H),6.27(s,1H),5.83(s,1H),5.57(s,1H),5.18(s,1H),2.34(s,3H),1.97(s,3H),1.20(s,3H). 13 C NMR(101MHz,CDCl3,ppm)δ152.2,151.3,146.3,145.6,136.8,136.3,135.5,134.9,134.8,132.2,131.1,130.3,129.3,129.1,129.0,128.7,128.4,128.2,128.0,127.8,127.7,126.8,126.5,126.3,125.2,124.7,124.1,124.0,121.2,117.4,117.3,112.3,55.5,21.3,20.7,19.6.

[0114] 3e: 1 H NMR(400 MHz,CDCl3,ppm)δ7.75-7.56(m,5H),7.38-7.15(m,10H),6.98(d,J=8.9 Hz,1H),6.85(d,J=8.9 Hz,1H),6.59(d,J=8.2 Hz,2H),6.52(d,J=8.2 Hz,2H),5.72(s,0H),5.56(s,1H),5.24(s,1H),2.33-2.23(m,1H),1.39(h,J=7.4 Hz,1H),0.71(t,J=7.3Hz,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.2,150.9,146.5,145.3,141.4,137.2,136.3,133.0,131.3,130.4,129.3,129.1,128.8,128.4,128.2,127.5,127.3,127.2,127.12,127.06,126.9,126.3,124.5,124.4,124.3,123.2,120.8,117.4,117.0,111.9,54.6,37.4,24.0,13.5.

[0115] 3f: 1 H NMR(400 MHz,CDCl3,ppm)δ7.79-7.55(m,5H),7.38-7.15(m,10H),6.97(d,J=8.9 Hz,1H),6.91-6.74(m,3H),6.63-6.50(m,2H),5.74(s,1H),5.51(s,1H),5.23(s,1H),1.07(s,9H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.20,150.77,149.93,146.59,144.93,136.88,136.37,133.20,131.36,130.44,129.43,129.06,128.82,128.30,128.23,127.58,127.13,127.01,126.96,126.72,126.29,124.55,124.41,124.28,124.19,123.50,120.76,117.45,116.80,112.12,54.53,34.29,31.07.

[0116] 3g: 1 H NMR(400 MHz,CDCl3,ppm)δ7.65(dd,J=21.5,9.0 Hz,5H),7.37-7.14(m,2H),7.00(d,J=8.9 Hz,10H),6.84(d,J=8.9 Hz,1H),6.56(d,J=8.8 Hz,2H),6.33(d,J=8.8 Hz,2H),5.73(s,2H),5.53(s,1H),5.22(s,1H),3.55(s,3H). 13 C NMR(101 MHz,CDCl3,ppm)δ158.5,152.3,151.0,146.7,145.0,136.4,133.1,132.5,131.5,130.5,129.5,129.2,129.0,128.7,128.50,128.45,127.7,127.3,127.2,127.1,126.5,124.7,124.5,124.4,123.4,121.0,117.5,117.1,112.9,112.0,55.0,54.9.

[0117] 3h: 1H NMR(400 MHz,CDCl3,ppm)δ7.66(dt,J=8.0,5.9 Hz,5H),7.39-7.27(m,13H),7.24-7.21(m,1H),7.06(d,J=8.3 Hz,2H),7.00(d,J=8.9 Hz,1H),6.87(d,J=8.9Hz,1H),6.69(d,J=8.3 Hz,2H),5.76(s,1H),5.59(s,1H),5.28(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.3,150.9,146.4,144.8,140.3,139.4,139.0,136.1,132.9,131.5,130.6,129.4,129.1,128.8,128.6,128.38,128.37,127.8,127.7,127.2,127.20,127.18,127.1,126.7,126.4,125.8,124.6,124.4,123.5,120.9,117.4,116.7,111.7,54.5.

[0118] 3i: 1 H NMR(400 MHz,CDCl3,ppm)δ8.23-8.07(m,1H),7.75-7.66(m,3H),7.60-7.46(m,2H),7.44-7.28(m,4H),7.24(dd,J=6.7,2.9 Hz,3H),7.23-7.14(m,3H),7.10-7.01(m,2H),7.02-6.94(m,3H),6.94-6.84(m,2H),6.55(dd,J=7.1,1.2 Hz,1H),5.75(s,2H),5.38(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.5,150.9,146.5,145.3,136.2,135.6,133.3,131.6,131.3,130.7,130.3,129.2,129.1,128.9,128.8,128.1,127.8,127.4,127.3,127.0,126.9,126.7,125.9,125.7,125.5,125.3,124.8,124.7,124.4,124.18,124.15,121.1,117.1,116.9,111.5,54.4.

[0119] 3j:1 H NMR(400 MHz,CDCl3,ppm)δ7.65(m,J=16.0,6.9,3.3 Hz,5H),7.42-7.15(m,2H),7.00(d,J=8.9 Hz,1H),6.86(d,J=8.9 Hz,1H),6.64-6.54(m,1H),6.47(t,J=8.8 Hz,1H),5.67(s,1H),5.61(s,1H),5.23(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ161.6(d,J=244 Hz),152.4,150.9,146.2,144.2,135.92,135.87(d,J=3 Hz),132.7,131.5,130.6,129.3,129.12,129.0(d,J=8 Hz)128.5,128.4,127.7,127.4,127.3,127.2,126.5,124.6,124.4,124.2,123.7,120.9,117.3,116.8,114.3,114.1,111.4,54.6.

[0120] 3k: 1 H NMR(400 MHz,CDCl3,ppm)δ7.75-7.56(m,5H),7.41-7.07(m,10H),7.00(d,J=8.9 Hz,1H),6.86(d,J=9.0 Hz,1H),6.81-6.73(m,2H),6.59-6.50(m,2H),5.64(s,1H),5.59(s,1H),5.21(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ138.4,135.8,132.8,132.7,131.6,130.7,129.3,129.1,128.9,128.7,128.5,128.4,127.7,127.5,127.4,127.3,127.2,126.5,124.6,124.4,124.2,123.8,120.9,117.3,116.7,111.3,54.4.

[0121] 3l: 1H NMR(400 MHz,CDCl3,ppm)δ7.79(d,J=8.8 Hz,2H),7.68-7.57(m,3H),7.44(d,J=7.3 Hz,2H),7.39-7.34(m,3H),7.33-7.27(m,3H),7.25-7.21(m,1H),7.07(d,J=9.0 Hz,1H),6.85(d,J=8.9 Hz,1H),6.77(dd,J=5.0,3.0 Hz,1H),6.53(dd,J=2.9,1.2Hz,1H),6.23(dd,J=5.0,1.1 Hz,1H),5.72(s,1H),5.55(s,1H),5.27(s,1H). 13 C NMR(101MHz,CDCl3,ppm)δ152.3,151.0,146.8,139.9,139.3,136.0,133.1,131.6,130.7,129.6,129.1,128.9,128.5,127.93,127.87,127.41,127.35,126.8,126.4,124.6,124.5,124.2,124.1,124.0,123.1,120.8,117.7,116.7,112.0,54.1.

[0122] 3m: 1 H NMR(400 MHz,CDCl3,ppm)δ7.73-7.61(m,5H),7.41-7.29(m,4H),7.22-7.18(m,2H),7.09(d,J=7.8 Hz,2H),7.01(d,J=8.9 Hz,1H),6.98-6.88(m,2H),6.84(dd,J=8.4,6.8 Hz,2H),6.69(dt,J=7.1,1.4 Hz,2H),5.80(s,1H),5.64(s,1H),5.25(s,1H),2.32(s,3H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.3,151.0,145.6,143.5,140.0,136.7,136.4,132.9,131.4,130.5,130.0,129.1,128.8,128.5,128.3,127.6,127.4,127.2,127.2,127.0,126.4,124.6,124.4,124.3,123.1,120.8,117.3,117.0,111.7,54.2,21.1.

[0123] 3n: 1 H NMR(400 MHz,CDCl3,ppm)δ7.75(d,J=8.3 Hz,1H),7.62(td,J=8.0,6.0Hz,4H),7.42-7.25(m,3H),7.17(dt,J=7.3,1.4 Hz,1H),7.08(ddq,J=10.0,4.0,2.1,1.5Hz,3H),6.97(d,J=8.9 Hz,1H),6.85(dd,J=8.3,6.3 Hz,2H),6.75(t,J=7.6 Hz,2H),6.56(d,J=7.2Hz,2H),5.70(s,1H),5.68(s,1H),5.62(s,1H),2.05(s,3H). 13 C NMR(101MHz,CDCl3,ppm)δ152.2,151.0,146.3,145.2,139.6,137.5,136.8,134.5,132.7,131.4,130.7,130.4,129.2,129.0,128.8,128.2,127.6,127.4,127.2,127.0,126.9,126.8,126.3,124.6,124.4,124.3,122.8,120.9,117.2,116.9,111.2,49.1,19.9.

[0124] 3o: 1 H NMR(400 MHz,CDCl3,ppm)δ7.71-7.60(m,5H),7.39-7.27(m,4H),7.19-7.12(m,2H),7.00(d,J=8.9 Hz,1H),6.95-6.75(m,6H),6.68-6.62(m,2H),5.70(s,1H),5.58(s,1H),5.20(s,1H),3.76(s,3H). 13 C NMR(101 MHz,CDCl3,ppm)δ158.6,152.2,150.9,145.7,140.0,138.8,136.5,132.9,131.4,130.5,129.1,128.8,128.4,128.3,127.6,127.3,127.2,127.1,127.0,126.3,124.6,124.4,124.3,122.8,120.8,117.3,116.9,114.6,113.9,111.6,55.2,53.6.

[0125] 3p:1 H NMR(400 MHz,CDCl3,ppm)δ7.81(dd,J=8.4,1.1 Hz,1H),7.66-7.48(m,4H),7.36(ddd,J=8.3,6.8,1.3 Hz,1H),7.30-7.14(m,4H),7.13-6.99(m,3H),6.92(dd,J=8.3,1.2 Hz,1H),6.84(dd,J=8.6,7.0 Hz,2H),6.81-6.74(m,1H),6.71(dd,J=8.3,6.6Hz,2H),6.63(dt,J=7.0,1.5 Hz,2H),5.65(s,1H),5.48(s,1H),3.28(s,3H). 13 C NMR(101MHz,CDCl3,ppm)δ151.92,151.87,142.9,140.0,135.7,135.2,132.5,131.1,130.3,129.9,129.6,128.8,128.6,128.5,128.1,127.4,127.2,126.9,126.8,126.6,126.1,124.5,124.1,124.0,123.7,122.1,120.7,117.3,117.3,114.7,111.5,57.1,51.4.

[0126] 3q: 1 H NMR(400 MHz,CDCl3,ppm)δ7.75-7.61(m,5H),7.43-7.28(m,4H),7.23-7.11(m,4H),7.00(d,J=8.9 Hz,1H),6.97-6.79(m,4H),6.68(dd,J=8.3,1.3 Hz,2H),5.70(s,1H),5.62(s,1H),5.24(s,1H),2.44(s,3H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.4,150.9,145.1,143.2,139.9,137.1,136.0,132.9,131.5,130.6,129.1,128.8,128.4,128.3,127.8,127.6,127.31,127.25,127.1,126.5,124.6,124.4,124.3,123.3,120.9,117.3,116.9,111.6,53.9,15.7.

[0127] 3r: 1H NMR(400 MHz,CDCl3,ppm)δ7.71-7.55(m,5H),7.36-7.22(m,7H),7.22-7.15(m,2H),6.97(d,J=9.0 Hz,1H),6.94-6.86(m,1H),6.84(d,J=8.9 Hz,1H),6.79(t,J=7.7 Hz,2H),6.63(dt,J=7.1,1.4 Hz,2H),5.79(s,1H),5.56(s,1H),5.20(s,1H),1.26(s,9H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.3,150.9,150.0,145.6,143.3,140.1,136.4,133.0,131.4,130.5,129.1,128.8,128.5,128.3,127.6,127.4,127.3,127.1,127.0,126.8,126.3,126.2,124.6,124.4,124.3,123.1,120.8,117.3,117.0,111.9,54.1,34.5,31.4.

[0128] 3s: 1 H NMR(400 MHz,CDCl3,ppm)δ7.72-7.65(m,5H),7.61-7.55(m,2H),7.55-7.50(m,2H),7.44(t,J=7.6 Hz,2H),7.41-7.30(m,7H),7.03(d,J=8.9 Hz,1H),6.93(dd,J=8.2,5.5 Hz,2H),6.86(dd,J=8.4,6.8 Hz,2H),6.78-6.71(m,2H),5.84(s,1H),5.70(s,1H),5.36(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.4,151.0,145.4,145.1,140.6,140.0,139.9,136.12,132.9,131.5,130.6,129.2,128.9,128.8,128.6,128.3,127.9,127.8,127.6,127.4,127.3,127.2,127.1,127.0,126.5,124.7,124.44,124.35,123.5,120.9,117.4,117.02,116.99,111.8,54.2.

[0129] 3t: 1 H NMR(400 MHz,CDCl3,ppm)δ7.65(dt,J=8.1,2.9 Hz,5H),7.48(d,J=8.1Hz,2H),7.40-7.21(m,7H),6.98(d,J=9.0 Hz,1H),6.93-6.84(m,2H),6.81(dd,J=8.4,6.8 Hz,2H),6.67-6.61(m,2H),5.66(s,1H),5.59(s,1H),5.38(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.6,150.9,140.0,143.8,139.7,135.2,132.7,131.5,130.7,129.22(d,J=3.3 Hz),129.17,128.9,128.5,128.3,127.9,127.6,127.4,127.2,127.1,126.8,126.1(q,J=3.8 Hz),125.5,124.6,124.4,124.3,124.10(d,J=270 Hz),124.06,121.1,117.2,116.9,111.4,54.3.

[0130] 3u: 1 H NMR(400 MHz,CDCl3,ppm)δ7.64(dd,J=8.9,2.5 Hz,5H),7.44(d,J=7.2Hz,3H),7.38-7.24(m,5H),6.97(d,J=8.9 Hz,1H),6.91-6.82(m,2H),6.79(dd,J=8.3,6.7 Hz,2H),6.65-6.58(m,2H),5.67(s,1H),5.56(s,1H),5.39(s,1H). 13C NMR(101 MHz,CDCl3,ppm)δ152.5,150.9,150.9,146.8,143.9,143.9,139.3,134.8,133.1,131.5,131.3,130.8(d,J=32 Hz),130.8,129.2,129.0,128.8,128.8,128.6,128.0,127.9,127.3,127.2,127.0,125.4,125.1(q,J=3.7 Hz),124.6,124.3,124.0(d,J=271 Hz)123.9,123.5(q,J=3.8 Hz),123.5,121.4,117.5,116.1,110.5,54.1.

[0131] 3v: 1 H NMR(400 MHz,CDCl3,ppm)δ7.60-7.50(m,5H),7.33-7.14(m,5H),7.13-7.04(m,4H),6.89(d,J=8.9 Hz,1H),6.85-6.68(m,4H),6.63-6.53(m,2H),5.56(d,J=1.6Hz,2H),5.19(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.5,150.9,144.9,144.5(d,J=1.9Hz),139.8,135.6,132.79,132.75,131.5,130.6,129.3,129.2,128.9,128.5,128.3,127.6,127.3,127.3,127.2,127.1,126.7,124.6,124.4,124.3,123.6,121.0,117.3,116.9,111.5,53.9.

[0132] 3w: 1 H NMR(400 MHz,CDCl3,ppm)δ7.68-7.61(m,5H),7.33-7.25(m,3H),7.23(q,J=2.2,1.3 Hz,1H),6.93-6.77(m,4H),6.68-6.62(m,2H),5.66(s,1H),5.65(s,1H),5.27(s,1H). 13C NMR(101 MHz,CDCl3,ppm)δ152.5,150.9,148.1,144.1,139.7,135.3,134.7,132.7,131.5,130.7,130.5,129.2,128.8,128.4,128.3,127.7,127.6,127.4,127.27,127.25,127.2,127.1,126.7,125.6,124.6,124.4,123.9,121.0,117.3,116.9,111.4,54.2.

[0133] 3x: 1 H NMR(400 MHz,CDCl3,ppm)δ7.78-7.63(m,5H),7.58-7.51(m,1H),7.43(dt,J=7.2,1.3 Hz,1H),7.38(d,J=7.6 Hz,1H),7.36-7.27(m,2H),7.16-7.07(m,1H),7.02(d,J=9.0 Hz,1H),6.98-6.91(m,1H),6.92-6.82(m,6H),6.81-6.75(m,2H),6.06(s,1H),5.63(s,1H),5.55(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.8,151.4,150.4,144.3,139.7,135.4,132.9,131.5,130.8,129.0,128.8,128.3,127.6,127.5,127.4,127.3,127.19,127.15,127.0,126.9,124.6,124.5,124.27,124.26,123.79,123.76,120.9,117.5,116.4,111.3,49.4.

[0134] 3y: 1 H NMR(400 MHz,CDCl3,ppm)δ7.99(s,1H),7.70-7.52(m,4H),7.39-7.16(m,9H),6.97(d,J=8.9 Hz,1H),6.93-6.85(m,1H),6.83-6.75(m,2H),6.64-6.58(m,2H),6.07(s,1H),5.57(s,1H),5.26(s,1H). 13C NMR(101 MHz,CDCl3,ppm)δ151.0,147.8,146.9,145.8,139.8,136.5,132.9,132.7,131.1,129.34,129.29,128.8,128.3,127.9,127.39,127.36,127.20,127.15,127.1,125.5,125.4,124.2,124.1,123.4,117.4,117.2,115.1,113.8,54.5.

[0135] 3z: 1 H NMR(400 MHz,CDCl3,ppm)δ7.77-7.58(m,5H),7.46-7.28(m,9H),7.27-7.23(m,2H),7.22-7.12(m,3H),6.92-6.86(m,2H),6.84-6.78(m,2H),6.71-6.65(m,2H),5.85(s,1H),5.82(s,1H),5.28(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.2,148.6,146.2,144.7,140.2,137.0,136.4,132.5,131.2,130.33,130.31,129.29,129.13,129.11,128.7,128.6,128.5,128.3,127.9,127.6,127.49,127.46,127.1,126.91,126.90,126.4,124.6,124.5,124.4,123.8,120.8,117.8,111.9,54.5.

[0136] 3aa: 1 H NMR(400 MHz,CDCl3,ppm)δ7.75-7.57(m,1H),7.45(d,J=8.3 Hz,1H),7.36-7.28(m,1H),7.26(dd,J=10.9,4.1 Hz,1H),7.18(ddd,J=8.4,7.6,2.1 Hz,1H),6.92-6.84(m,1H),6.81(t,J=7.5 Hz,1H),6.72-6.66(m,1H),5.86(s,1H),5.84(s,1H),5.28(s,1H),1.35(s,2H). 13C NMR(101 MHz,CDCl3,ppm)δ152.2,151.0,148.7,146.2,144.5,140.3,136.4,133.9,132.4,131.1,130.3,130.2,129.11,129.08,128.9,128.7,128.5,128.2,127.6,127.5,127.4,127.05,127.04,126.87,126.85,126.3,125.7,124.53,124.49,124.4,123.9,120.8,117.6,111.9,54.5,34.7,31.4.

[0137] 3ba: 1 H NMR(400 MHz,CDCl3,ppm)δ7.72-7.59(m,9H),7.50-7.40(m,4H),7.39-7.29(m,5H),7.28-7.11(m,5H),6.93-6.87(m,2H),6.86-6.80(m 2H),6.72-6.66(m,2H),5.92(s,1H),5.82(s,1H),5.29(s,1H). 13 C NMR(101 MHz,CDCl3,ppm)δ152.2,148.6,146.2,145.0,140.8,140.7,140.2,136.3,136.0,132.5,131.2,130.4,129.9,129.7,129.19,129.17,128.9,128.8,128.6,128.3,127.6,127.53,127.51,127.48,127.3,127.18,127.15,127.0,126.42,124.7,124.6,124.4,123.7,120.8,117.9,111.8,54.5.

[0138] 3ca: 1 H NMR(400 MHz,CDCl3,ppm)δ7.90-7.83(m,4H),7.68(m,6H),7.55-7.42(m,4H),7.40-7.30(m,5H),7.28-7.24(m,3H),7.23-7.10(m,4H),6.97-6.87(m,2H),6.88-6.82(m,2H),6.75-6.67(m,2H),5.92(s,1H),5.87(s,1H),5.30(s,1H). 13C NMR(101 MHz, CDCl3, ppm) δ152.2,148.7,146.1,144.8,140.2,136.3,134.5,133. 4,132.8,132.5,131.5,130.4,130.3,129.1,128.8,128.5,128.3,128.1 8,128.15,127.8,127.6,127.52,127.48,127.3,127.13,127.11,127.0, 126.42,126.38,124.7,124.6,124.4,123.8,120.8,117.8,111.8,54.5.

[0139] 3da: 1 H NMR (400 MHz, CDCl3, ppm) δ7.85-7.60(m,9H),7.45-7.26(m,5H),7.26-7.19(m,5H),6.95(t,J=7.4 Hz,1H),6.89(d,J=8.9 Hz,1H),6.83(t,J=7.7 Hz,2H),6.61-6.55(m,2H),5.96(s,1H),5.59(s,1H),5.28(s,1H). 13 C NMR (101MHz, CDCl3, ppm) δ152.1,147.8,146.3,146.1,139.6,139.5,136.0,132. 9,131.8,131.4(q,J=33Hz),130.9,129.5,129.2,128.6,128.5,128.42,128.40,, 127.4,127.3,127.31,127.27,126.5,125.2,124.8,124.7,124.3,123.4(q,J=271 Hz), 123.1, 122.0, 121.3 (dt, J = 7.7Hz, 3.8Hz), 120.7, 119.3, 118.4, 111.4, 54.4.

[0140] Application Examples

[0141] Compound 3a was subjected to a petasis reaction in the presence of a catalytic vinyl borate, as shown in the following reaction, to afford the target product in 80% yield and 99% enantioselectivity.

[0142]

[0143] Specific experimental procedures: Morpholine (11 μL, 0.12 mmol, 1.2 eq) was added to a magnetically stirred mixture containing 2-hydroxy-5-methoxybenzaldehyde (15 mg, 0.1 mmol, 1 eq), Molecular sieves (80 mg), catalyst (9 mg, 0.02 mmol, 0.2 mol%), and dibutyl vinyl borate (26.4 μL, 0.12 mmol, 1.2 eq) were added to toluene (2 mL). The mixture was stirred at 22°C for 3 hours and then filtered through celite. The celite was washed with toluene. The combined filtrates were washed three times with dilute brine, dried over anhydrous sodium sulfate, filtered, and concentrated on a rotary evaporator to yield the product as an oil (21 mg, 80% yield). 1 H NMR (400MHz, CDCl3): δ10.46 (s, 1H), 6.76-6.66 (m, 2H), 6.55 (d, J = 2.1Hz, 1H), 5.98 (dt, J = 17 .2,9.7Hz,1H),5.34-5.18(m,2H),3.82(d,J=9.5Hz,1H),3.72(s,7H),2.57(d,J=38.6Hz,4H). 13 C NMR (100MHz, CDCl3): δ152.7,150.0,134.6,124.4,119.2,116.8,114.3,114.2,113.7,74.6,74.5,66.7,55.5,50.9.

[0144] Obviously, the above embodiments are merely examples for clarity of explanation and are not intended to limit the implementation methods. Those skilled in the art will appreciate that other variations or modifications can be made based on the above description. It is not necessary and impossible to enumerate all implementation methods here. Obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. An optically active diphenol having both central chirality and axial chirality, characterized in that The general structural formula of the optically active diphenol is shown below: Among them, Ar 1 is an aromatic compound or heteroaryl compound with different substituents, Ar 3 Aryl compounds with different substituents, Ar 2 is an aromatic compound or heteroaryl compound with different substituents, Ar 4 is halogen or hydrogen.

2. The optically active diphenol having both central chirality and axial chirality according to claim 1, characterized in that The Ar 1 C6H5, 4-MeC6H4, 4-OMeC6H4, 4- n PrC6H4、4- t One or more of BuC6H4, 4-ClC6H4, 4-FC6H4, 4-PhC6H4, 2-MeC6H4, 2-thiophenyl, Naphthyl and 2,4,6-triMeC6H2.

3. The optically active diphenol having both central chirality and axial chirality according to claim 1, characterized in that The Ar 2 C6H5, 4-MeC6H4, 4-OMeC6H4, 4-SMeC6H4, 4- t One or more of BuC6H4, 4-PhC6H4, 4-CF3C6H4, 4-ClC6H4, 3-CF3C6H4, 3-ClC6H4, 2-MeC6H4, 2-OMeC6H4, and 2-thiophenyl.

4. The optically active diphenol having both central chirality and axial chirality according to claim 1, wherein The Ar 3 C6H5, 4- t One or more of BuC6H4, 4-PhC6H4, Naphthyl, 3,5-diCF3C6H3; the Ar 4 Halogens include F, Cl, and Br.

5. The optically active diphenol having both central chirality and axial chirality according to claim 1, characterized in that: The optically active diphenol includes any one of the following structures:

6. A method for preparing an optically active diphenol having both central chirality and axial chirality according to any one of claims 1 to 5, characterized in that: The following steps are involved: Under an inert atmosphere, 1-arylethynyl-2-naphthol derivatives were 8-Arylhydroxymethyl-2-naphthol derivatives The product is mixed with a chiral phosphoric acid catalyst, and a molecular sieve additive and a reaction solvent are added, and heated for reaction to obtain the optically active diphenol.

7. The preparation method according to claim 6, characterized in that The 1-arylethynyl-2-naphthol derivative 8-Arylhydroxymethyl-2-naphthol derivatives The ratio of the amount of substance is (1~2):(1~2); The heating reaction temperature is 25-70°C and the time is 4-10 hours.

8. The preparation method according to claim 6, characterized in that The chiral phosphoric acid catalyst includes one or more of the following structures: One or more of; Among them, R 1 is one or more of H, 2-naphthyl, 9-anthryl, 4-PhC6H4, TMS, 4,6-dihydropyren-1-yl, and 3,4,5-triFC6H2; R 2 One or more of 4-tBuC6H4, 4-naphthylC6H4, 2,4,6-triipr-C6H2, 4-CF3C6H4, and 3,5-diCF3C6H3; R 3 is H or 4-PhC6H4; R 4 One or more of 4-CF3C6H4, 4-NO2C6H4, 3,5-diClC6H3, 3,5-diCF3C6H3, 4-PhC6H4, 2-naphthyl, 3,5-diCH3C6H3, 3,5-ditBuC6H3, SiPh3, 3,5-PhC6H3, and 3,5-di(3,5-diCF3C6H3)C6H3; R 5 It is one or more of phenyl, 2-naphthyl, 9-anthryl, 4-ClC6H4, and 3,5-diClC6H3.

9. The preparation method according to claim 6, characterized in that The additive is selected from MS, MS and One or more of MS; The reaction solvent is one or more of CH2Cl2, CHCl3, CCl4, DCE, Toluene, PhCF3, PhCl, CH3CN and THF; The inert gas of the inert atmosphere is selected from nitrogen and / or argon.

10. Use of the NAPOL diphenol product according to any one of claims 1 to 5 in catalyzing a petasis reaction involving vinyl borate.

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