Axial chiral phenanthroline ligand as well as preparation method and application thereof

Abstract

The invention discloses an axially chiral phenanthroline ligand as well as a preparation method and application thereof. The axially chiral phenanthroline ligand has a structure as shown in a general formula (I), wherein an axially chiral part of the ligand is a binaphthyl structure A; r1 in the binaphthalene structure A of the ligand is any one of alkyl, phenyl and substituted phenyl; and the part B of the ligand is selected from any one of hydrogen, halogen, phenyl and substituted phenyl or is the same as A. According to the invention, an axially chiral phenanthroline ligand and a copper salt form a complex catalyst in situ in a reaction system, and a diverse substituted 1, 1 '-biphenyl-2'-iodine-2-amide compound with high optical purity and a 1, 1 '-biphenyl-2'-iodine-2-amide compound with high optical purity are respectively synthesized by catalyzing asymmetric ring-opening amination and ring-opening acylation of a ring-shaped diaryl iodonium salt. According to the present invention, in the reaction of the 1, 1 '-biphenyl-2'-iodine-2-carboxylic ester compound, the good to excellent yield, the enantioselectivity and the good substrate universality are represented, and the good industrial application prospect is provided. The invention belongs to the field of asymmetric synthetic chemistry.

Description

Technical Field

[0001] This invention belongs to the field of asymmetric synthetic chemistry, specifically relating to a novel class of axially chiral phenanthroline ligands, their preparation methods, and applications. Catalysts formed by these ligands and copper salts can be used for asymmetric ring-opening amination and acyl oxidation reactions of cyclic diaryliodonium salts to synthesize highly optically pure, diverse substituted 1,1'-biphenyl-2'-iodo-2-amide compounds and 1,1'-biphenyl-2'-iodo-2-carboxylic acid ester compounds, exhibiting high catalytic activity and enantioselectivity. Background Technology

[0002] Axially chiral biaryl structures are not only widely found in natural products and drug molecules, but also serve as the core framework for many chiral ligands and catalysts, playing a crucial role in asymmetric synthesis. Since Noyori et al. pioneered the development of the 1,1'-binaphthyl-2,2'-bis(diphenylphosphine) ligand (BINAP), many novel axially chiral biaryl ligands have been continuously developed and widely applied in transition metal-catalyzed asymmetric synthetic reactions (Noyori, R. et al. J. Am. Chem. Soc. 1979, 101, 3129-3131; Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029-3070; Yudin, A K et al. Chem. Rev. 2003, 103, 3155-3212; Brunel, J. M. Chem. Rev. 2005, 105, 857–897). phenanthroline, as a classic N,N bidentate ligand, has shown broad application prospects in organic synthesis due to its unique planar rigid structure and ease of coordination with various transition metals. Chiral ligands with phenanthroline as the core coordination unit are also gradually being applied to the field of asymmetric catalysis. In 1987, Gladiali et al. synthesized a chiral phenanthroline ligand containing (S)-3-isobutyl and used it for the metal Rh-catalyzed asymmetric hydrogenation of aromatic ketones (Gladiali, S. et al. J. Organomet. Chem. 1987, 327, C15–C17). In 2011, Yamamoto et al. synthesized a class of axially chiral phenanthroline ligands using the axially chiral binaphthyl skeleton as a chiral source and applied them to iron-catalyzed asymmetric epoxidation reactions of alkenes, achieving a series of epoxides with high yields and excellent enantioselectivity (Yamamoto, H. et al. J. Am. Chem. Soc. 2011, 133, 8432–8435). In 2014, Nishiyama's group reported BinThro, a novel N,N,O-tridentate phenanthroline ligand prepared from BINOL. This ligand combines the binaphthyl structure with the phenanthroline unit via C-C bonds, enabling the asymmetric reduction synthesis of a series of chiral alcohols from aldehydes (Nishiyama, H. et al. Chem. Commun. 2014, 50, 13224–13227). In 2020, Bach's research group designed and synthesized a novel class of chiral phenanthroline ligands by combining an acetylenic bridge with the C4 position of an octahydrobridged cyclic lactam. The catalyst formed by this ligand and silver salt enabled the enantioselective amination of aliphatic methylene groups in pyridones and quinolones (Bach, T. et al. J. Am. Chem. Soc. 2020, 142, 7374–7378).Chiral phenanthroline ligands have undergone decades of development, but most remain centrally chiral, and the types of asymmetric catalytic reactions applicable to them are limited. Transition metal-catalyzed asymmetric ring-opening reactions of cyclic diaryl compounds are one of the most efficient methods for constructing axially chiral biaryl compounds. Among these, the asymmetric ring-opening reaction of cyclic diaryl iodonium salts can be used to synthesize various axially chiral biaryl compounds containing carbon-iodine bonds. These products can serve as synthetic intermediates for many axially chiral compounds and have significant application prospects. Currently, the chiral ligands suitable for these reactions are mainly chiral bisoxazoline and pyridine oxazoline ligands, resulting in relatively simple catalytic systems and limited reaction types. The enantioselectivity of some reactions needs improvement. Developing novel chiral ligands and catalysts for the synthesis of diverse substituted 1,1'-biphenyl-2'-iodo-2-amides and 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters has high practical application value. Summary of the Invention

[0003] The purpose of this invention is to provide a novel class of axially chiral phenanthroline ligands (I).

[0004] Another objective of this invention is to provide a method for synthesizing the above-mentioned chiral ligands.

[0005] Another object of the present invention is to provide the use of the above-mentioned chiral ligands, namely, to form catalysts with copper salts for the asymmetric synthesis of 1,1'-biphenyl-2'-iodo-2-amide compounds and 1,1'-biphenyl-2'-iodo-2-carboxylic acid ester compounds with diverse substitutions.

[0006] This invention provides an axially chiral phenanthroline ligand, characterized in that the axially chiral ligand is represented by the following general formula (Ⅰ):

[0007]

[0008]

[0009] In the above formula (Ⅰ):

[0010] The B portion of the axially chiral phenanthroline ligand is any one of hydrogen atom, halogen, phenyl, substituted phenyl or the same as A;

[0011] The axial chirality marked with * indicates either R-configuration or S-configuration;

[0012] R 1 Selected independently from C 1-6 Any one of alkyl, phenyl, and substituted phenyl groups;

[0013] R 2 -R 3Each is independently selected from hydrogen, phenyl, or substituted phenyl.

[0014] In a preferred experimental scheme of the present invention, when R 1 C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or hexyl; when the R 1 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group.

[0015] In a preferred experimental scheme of the present invention, when R 2 -R 3 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group.

[0016] In a preferred experimental scheme of the present invention, when B is a substituted phenyl group, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group.

[0017] The present invention also provides a method for preparing the axially chiral phenanthroline ligand, characterized by the following steps:

[0018] Compound 3 was prepared by reacting compound 1 and compound 2 in an organic solvent under an inert gas environment with the help of copper salt, ligand and base;

[0019]

[0020] Y in compound 2 1 Selected from chlorine, bromine, or iodine atoms; Y 2 Selected from hydrogen atom, phenyl, substituted phenyl, or with Y 1 same;

[0021] In compound 3, B is any one of hydrogen atom, halogen, phenyl, substituted phenyl, or the same as A.

[0022] In this invention, the organic solvent is a solvent commonly used in the field of organic synthesis. The organic solvent is one or more of the following: methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and dimethyl sulfoxide; preferably dimethyl sulfoxide.

[0023] In this invention, the inert gas includes one or more of argon, helium, neon, and krypton;

[0024] In this invention, the base is a base commonly used in the field of organic synthesis, including one of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, sodium phosphate, sodium methoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, calcium hydride, n-butyllithium, sec-butyllithium, tert-butyllithium, diisopropylaminolithium, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, and pyridine;

[0025] In this invention, the copper salt is one of copper chloride, copper bromide, cuprous chloride, cuprous bromide, cuprous iodide, copper acetate, copper acetylacetone, copper perchlorate, copper trifluoroacetate, copper tetrafluoroborate, copper tetraacetonitrile hexafluorophosphate, cuprous cyanide, cuprous thiocyanate, cuprous thiophene-2-carboxylate, and cuprous oxide.

[0026] In this invention, the ligand is an oxalamide ligand;

[0027] In this invention, the reaction temperature is the conventional reaction temperature for this type of reaction in the field of organic synthesis, for example, 50°C;

[0028] In this invention, the reaction time is the conventional reaction time for this type of reaction in the field of organic synthesis, and the reaction time is 1-60h, for example 24h;

[0029] In this invention, the molar concentration of the reactive compound in the organic solvent is 0.01-2 mol / L, for example, 0.5 mol / L;

[0030] In this invention, the synthesis reaction is further performed under reduced pressure for solvent removal after completion.

[0031] In this invention, the synthesis reaction is followed by a quenching process. The quenching solution can be a conventional quenching solution for this type of reaction in the field of organic synthesis, such as a saturated ammonium chloride solution;

[0032] In this invention, after the synthesis reaction is completed, a post-processing step is also included. The post-processing step can be a conventional post-processing step in the art, and the post-processing step includes one or more steps such as extraction, washing, drying, and column chromatography.

[0033] In this invention, the extractant can be a conventional extractant in the field of organic synthesis, including ethyl acetate, dichloromethane, chloroform, and diethyl ether; the washing solution can be a conventional washing solution in the field, such as a saturated sodium chloride solution; the drying can be done using a conventional drying agent in the field, such as anhydrous sodium sulfate or anhydrous magnesium sulfate; the column chromatography can be conventional silica gel column chromatography in the field of organic synthesis, and the eluent used in the column chromatography can be a conventional eluent in the field of organic synthesis, such as one or a mixture of several of petroleum ether, dichloromethane, ethyl acetate, or methanol.

[0034] The present invention also provides a method for synthesizing axially chiral, diversified substituted 1,1'-biphenyl-2'-iodo-2-amide compounds, comprising the following steps: in an inert gas environment, the above-mentioned axially chiral phenanthroline ligand is in situ complexed with a copper salt in an organic solvent to form a catalyst, then a base is added, and compounds 4 and 5 are reacted at a desired temperature and for a desired time to obtain compound 6.

[0035]

[0036] Among them, R 4 -R 11 Selected from hydrogen, alkyl, phenyl, substituted phenyl, halogen, or naphthyl; R 12 Selected from alkyl, phenyl, substituted phenyl, heteroaryl, or naphthyl;

[0037] The chiral axis marked with * is either S-configuration or R-configuration.

[0038] The present invention also provides a method for synthesizing axially chiral, diversified substituted 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters, comprising the following steps: in an inert gas environment, the above-mentioned axially chiral phenanthroline ligand is in situ complexed with a copper salt in an organic solvent to form a catalyst, then a base is added, and compounds 4 and 7 are reacted at a desired temperature and for a desired time to obtain compound 8.

[0039]

[0040] Among them, R 4 -R 11 Selected from hydrogen, alkyl, phenyl, substituted phenyl, halogen, or naphthyl; R 13 Selected from alkyl, phenyl, substituted phenyl, heteroaryl, or naphthyl;

[0041] The chiral axis marked with * is either S-configuration or R-configuration.

[0042] In this invention, when the R 4 -R 11 When the alkyl group is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl.

[0043] In this invention, when the R 4 -R 11 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group.

[0044] In this invention, when the R 12 When R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl; 12 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group; when the R 12 When the heteroaryl group is a furanyl, thiophene, indolyl, or pyridinyl group;

[0045] In this invention, when the R 13 When R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl; 13 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group; when the R 13 When the heteroaryl group is a furanyl, thiophenyl, pyrroleyl, quinolinyl, isoquinolinyl, or pyridyl;

[0046] In this invention, the organic solvent is a solvent commonly used in the field of organic synthesis, including one or more of methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, or dimethyl sulfoxide;

[0047] In this invention, the inert gas includes one or more of argon, helium, neon, and krypton;

[0048] In this invention, the copper salt may be one of the following: copper chloride, copper bromide, cuprous chloride, cuprous bromide, cuprous iodide, copper acetate, copper acetylacetone, copper perchlorate, copper trifluoroacetate, copper tetrafluoroborate, copper tetraacetonitrile hexafluorophosphate, cuprous cyanide, cuprous thiocyanate, cuprous thiophene-2-carboxylate, and cuprous oxide.

[0049] In this invention, the alkali includes one of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium phosphate, sodium phosphate, cesium carbonate, sodium methoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, calcium hydride, n-butyllithium, sec-butyllithium, tert-butyllithium, diisopropylaminolithium, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, or pyridine;

[0050] In this invention, the molar concentrations of compounds 4 and 5 in the organic solvent in the reaction formula are 0.01–5.0 M; for example, 0.1 M.

[0051] In this invention, the molar concentrations of compounds 4 and 7 in the organic solvent in the reaction formula are 0.01–5.0 M; for example, 0.1 M.

[0052] In this invention, the molar ratio of 4 to 5 in the above-mentioned reaction for preparing axially chiral, diversified substituted 1,1'-biphenyl-2'-iodo-2-amide compounds is 10:1 to 1:10; for example, 1:1.2.

[0053] In this invention, the molar ratio of 4 to 7 in the above-mentioned reaction for preparing axially chiral, diversified substituted 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters is 10:1 to 1:10; for example, 1:1.2.

[0054] In this invention, the molar ratio of 4 to base in the above-mentioned reaction for preparing axially chiral, diversified substituted 1,1'-biphenyl-2'-iodo-2-amide compounds is 10:1 to 1:10; for example, 1:2.

[0055] In this invention, the molar ratio of 4 to base in the above-mentioned reaction for preparing axially chiral, diversified substituted 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters is 10:1 to 1:10; for example, 1:3.

[0056] In this invention, the molar ratio of copper salt to axially chiral phenanthroline ligand in the above-mentioned reaction for preparing axially chiral, diversified substituted 1,1'-biphenyl-2'-iodo-2-amide compounds is 1:5 to 5:1; for example, 1:1.2.

[0057] In this invention, the molar ratio of copper salt to axially chiral phenanthroline ligand in the above-mentioned reaction for preparing axially chiral, diversified substituted 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters is 1:5 to 5:1; for example, 1:1.2.

[0058] In this invention, the reaction temperature is -50 to 50°C; for example, 40°C.

[0059] In this invention, the reaction time is 1 to 180 hours; for example, 24 hours.

[0060] In an embodiment of the present invention, after the reaction is completed, a post-processing step is further included. The post-processing step can be a conventional post-processing step in the field of organic synthesis, and the post-processing step includes a column chromatography step.

[0061] The term "er" refers to the enantiomeric ratio.

[0062] The positive and progressive effects of this invention are as follows:

[0063] This invention provides a novel axially chiral phenanthroline ligand, characterized by a binaphthyl axially chiral source and a phenanthroline group. The synthesis method involves using 1,1'-bi-2-naphthol (BINOL) and substituted BINOL as starting materials, along with halogen-containing 1,10-phenanthroline and its derivatives, to construct a carbon-oxygen bond through a coupling reaction between the binaphthyl axially chiral source and phenanthroline under copper catalysis. The target molecule of this invention has a concise and clear structure, is simple to operate, and can be prepared on a large scale. It has potential applications in the design of novel axially chiral ligands and the synthesis of axially chiral biaryl compounds.

[0064] The novel axially chiral phenanthroline ligand provided by this invention can be used as a chiral ligand to form a catalyst with copper salt in the reaction system, catalyzing the asymmetric ring-opening amination and acyl oxidation of cyclic diaryl iodonium salts to synthesize a variety of substituted 1,1'-biphenyl-2'-iodo-2-amides and 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters of axially chiral biaryl compounds. It also exhibits good to excellent yields and excellent enantioselectivity (up to 99:1) as well as good substrate versatility (compatible with at least dozens of reaction substrates), and has great prospects for industrial application. Attached Figure Description

[0065] Figure 1 The 1H NMR spectrum of axial chiral phenanthroline ligand 3a provided in an embodiment of the present invention;

[0066] Figure 2 The carbon NMR spectrum of axially chiral phenanthroline ligand 3a provided in an embodiment of the present invention;

[0067] Figure 3 The 3p 1H NMR spectrum of the axially chiral phenanthroline ligand provided in the embodiments of the present invention;

[0068] Figure 4 The 3p carbon NMR spectrum of the axially chiral phenanthroline ligand provided in the embodiments of the present invention;

[0069] Figure 5 The 3r 1H NMR spectrum of the axially chiral phenanthroline ligand provided in this embodiment of the invention;

[0070] Figure 6 The 3r carbon NMR spectrum of the axially chiral phenanthroline ligand provided in the embodiments of the present invention;

[0071] Figure 7 The 3s 1H NMR spectrum of the axially chiral phenanthroline ligand provided in the embodiments of the present invention;

[0072] Figure 8 The 3S carbon NMR spectrum of the axially chiral phenanthroline ligand provided in the embodiments of the present invention;

[0073] Figure 9 The 1H NMR spectrum of axially chiral 1,1'-biphenyl-2'-iodo-2-amide compound 6a provided in the embodiments of the present invention;

[0074] Figure 10 The carbon NMR spectrum of 6a of the axially chiral 1,1'-biphenyl-2'-iodo-2-amide compound provided in the embodiments of the present invention;

[0075] Figure 11 The 1H NMR spectrum of axially chiral 1,1'-biphenyl-2'-iodine-2-carboxylic acid ester compound 8a provided in the embodiments of the present invention;

[0076] Figure 12 The carbon NMR spectrum of 8a of the axially chiral 1,1'-biphenyl-2'-iodo-2-carboxylic acid ester compound provided in the embodiments of the present invention; Detailed Implementation

[0077] The present invention will be further described in detail below through specific embodiments, but this does not limit the scope of the present invention.

[0078] The information on the instruments and experimental materials used in the following embodiments is as follows:

[0079] All chemical reagents were purchased commercially available from companies such as Adamas, Bidex Pharmaceuticals, and Bailingwei. Thin-layer chromatography (TLC) was performed using SHF254 silica gel plates, and silica gel column chromatography used Nortech silica gel (300-400 mesh). TLC was performed using UV light (254nm). 1 HNMR and 13 CNMR was characterized using a Bruker AVANCE III 400MHz NMR instrument, with deuterated chloroform as the solvent. Chemical shift is measured in ppm, and coupling constants are measured in Hz. 1 In H NMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, heptet represents septet, and m represents multiplet. 13 In CNMR, δ represents chemical shift. High-resolution mass spectrometry was performed using a JEOC AccuTOF LC-plus 4G instrument with an ESI ion source. Enantiomer ratios (er) were determined using Shimadzu LC-20A high-performance liquid chromatography and Daicel Chiralpak and Chiralcel chiral columns.

[0080] Example 1:

[0081]

[0082] A dry 25 mL Schlenk tube was selected, and 1a (381 mg, 1.1 mmol), 2a (215 mg, 1.0 mmol), CuI (57 mg, 0.3 mmol), 9 (103 mg, 0.3 mmol), and K3PO4 (425 mg, 2.0 mmol) were added sequentially. The reaction system was purged with nitrogen three times, and anhydrous DMSO (3 mL) was added by syringe under nitrogen atmosphere. The reaction mixture was then stirred at 100 °C for 36 hours. The reaction was monitored by TLC to check for completeness. After the starting materials were completely converted and the reaction was cooled to room temperature, the reaction mixture was quenched with water and extracted with dichloromethane. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the organic solvent was removed under reduced pressure. The residue was purified by column chromatography (PE / EA = 5 / 1-3 / 1) to give a white solid 3a, 314 mg, with a yield of 60%. 1 H NMR(400MHz, CDCl3) δ9.04(dd,J=4.4,1.6Hz,1H),8.13(dd,J=8.0,1.6Hz,1H),7.94(d,J=8.0Hz,1 H),7.89(d,J=8.4Hz,1H),7.85(d,J=8.8Hz,2H),7.79(d,J=8.8Hz,1H),7.61(s,2H),7.58(d,J=8.4 Hz,1H),7.50(dd,J=8.0,4.4Hz,1H),7.43(ddd,J=8.4,6.4,1.2Hz,1H),7.39(d,J=8.4Hz,1H),7.3 6–7.29(m,3H),7.23(d,J=8.8Hz,1H),7.13–7.07(m,4H),7.01–6.96(m,2H),6.07(d,J=8.8Hz,1H). 13 C NMR (101MHz, CDCl3) δ162.3,150.5,150.2,145.4,145.0,142.2,139.7,139. 1,135.9,135.5,133.3,132.9,130.7,130.6,129.6,129.6,129.0,128.5,12 8.3(2C),127.9,127.8,127.2,127.1,126.7,126.6,126.4,126.2,125.8,12 5.7,125.4,125.1,124.7,122.9,120.2,113.0.HRMS(ESI-TOF)m / zCalcd.for C 38 H 25 N2O + [M+H] +Found: 525.1961; Found: 525.1964.

[0083] Example 2:

[0084]

[0085] The preparation method is the same as in Example 1. The product is a white solid, 440 mg, with a yield of 68%. 1 H NMR (400MHz, CDCl3) δ9.04 (dd, J=4.0, 1.6Hz, 1H), 8.14 (dd, J=8.0, 1.6Hz, 1H), 7.91 (t, J=8.8Hz, 2 H),7.87(d,J=8.8Hz,1H),7.84(d,J=8.0Hz,1H),7.78(d,J=8.8Hz,1H),7.62(d,J=1.2Hz,2H),7.5 6(d,J=8.4Hz,1H),7.51(dd,J=8.0,4.4Hz,1H),7.44(ddd,J=8.4,6.4,1.2Hz,1H),7.39(d,J=8.4H z,1H),7.35–7.32(m,1H),7.30(d,J=7.2Hz,1H),7.26(d,J=8.8Hz,2H),7.09(ddd,J=8.4,6.8,1.6 1H), 6.98 (d, J = 8.4Hz, 2H), 6.79 (d, J = 7.6Hz, 2H), 6.12 (d, J = 8.8Hz, 1H), 2.22 (s, 3H). 13 C NMR (101MHz, CDCl3) δ162.2,150.4,150.1,145.3,144.9,139.7,139.2,1 38.8,135.9,135.8,135.5,133.3,132.7,130.5,130.4,129.4,129.3,128 .9,128.4(3C),128.2,127.7,127.1,127.0,126.8,126.6,126.0,125.8,1 25.5,125.3,125.0,124.2,122.8,120.3,113.0,21.1.HRMS(ESI-TOF)m / z Calcd.for C 39 H 27 N2O + [M+H] + :539.2118; Found:539.2122.

[0086] Example 3:

[0087]

[0088] The preparation method is the same as in Example 1, yielding a yellow solid of 203 mg and a yield of 42%. 1 H NMR (400MHz, CDCl3) δ9.05 (dd, J=4.4, 1.6Hz, 1H), 8.17 (dd, J=8.0, 1.6Hz, 1H), 7.97 (d, J=8.4H z,1H),7.91(t,J=8.0Hz,2H),7.88(d,J=8.0Hz,1H),7.80(d,J=8.8Hz,1H),7.65(s,2H),7.54(d ,J=8.4Hz,1H),7.53(d,J=8.4Hz,1H),7.48–7.44(m,1H),7.40(t,J=7.2Hz,1H),7.35(d,J=4.0 Hz,2H),7.29(d,J=8.4Hz,1H),7.26–7.21(m,5H),7.16(t,J=7.6Hz,1H),6.05(d,J=8.4Hz,1H). 13 C NMR (101MHz, CDCl3) δ162.0,150.4,150.2,145.9,145.3,145.0,139.2,138.3,1 35.9,135.3,133.2,133.2,131.1,130.6,130.0,129.9,129.1,128.8,128.5(q,J C-F =32.3Hz),128.4,127.9,127.7,127.3,126.5,126.3,126.2,126.0,125.9,125.4,125.3,124.9,124.7(q,J C-F =4.0Hz), 124.4(q,J C-F =272.7Hz),123.0,120.3,112.3. 19 F NMR(376MHz,CDCl3)δ-62.3.HRMS(ESI-TOF)m / z Calcd.for C 39 H 24 N2OF3 + [M+H] + :593.1835; Found:593.1841.

[0089] Example 4:

[0090]

[0091] The preparation method is the same as in Example 1. The product is a white solid, 449 mg, with a yield of 72%. 1H NMR (400MHz, CDCl3) δ9.04(dd,J=4.4,1.6Hz,1H),8.15(dd,J=8.0,2.0Hz,1H),7.93(d,J=8.4Hz,1H),7.92(d,J=7.6Hz,1H),7.86(d, J=9.2Hz,1H),7.85(d,J=7.6Hz,1H),7.75(d,J=8.4Hz,1H),7.63(s,2H),5.93(d,J=8.6Hz,1H),7.52(dd,J=8.0,4.4Hz,1H),7.47–7. 41(m,2H),7.35(ddd,J=8.4,6.8,1.2Hz,2H),7.24(d,J=8.4Hz,1H),7.18(d,J=9.2Hz,1H),7.11(ddd,J=8.8,6.8,1.2Hz,1H),6.98(d ,J=8.0Hz,2H),6.85(d,J=8.0Hz,2H),5.93(d,J=8.8Hz,1H),2.80(hept,J=6.8Hz,1H),1.21(d,J=4.0Hz,3H),1.20(d,J=3.6Hz,3H). 13 C NMR (101MHz, CDCl3) δ162.2,150.4,150.1,147.0,145.3,144.9,139.6,13 8.9,135.9,135.8,133.3,132.8,130.5,130.4,129.5(2C),128.9,128.5, 128.3,127.8,127.2,127.1,126.8,126.7,126.1,125.8(2C),125.5,125. 3,125.1,124.7,122.9,120.1,113.0,33.7,24.3,24.0.HRMS(ESI-TOF)m / z Calcd.for C 41 H 31 N2O + [M+H] + :567.2431; Found:567.2422.

[0092] Example 5:

[0093]

[0094] The preparation method is the same as in Example 1, yielding a yellow solid of 391 mg and a yield of 45%. 1H NMR (400MHz, CDCl3) δ9.04 (dd, J=4.4, 2.0Hz, 1H), 8.12 (dd, J=8.0, 1.6Hz, 1H), 7.93 (d, J=8.8Hz, 1H), 7.9 1(d,J=7.6Hz,1H),7.86(d,J=8.4Hz,1H),7.85(d,J=8.8Hz,1H),7.72(d,J=8.8Hz,1H),7.60(s,2H),7.59 (d,J=8.0Hz,1H),7.49(dd,J=8.0,4.4Hz,1H),7.44(d,J=8.0Hz,2H),7.34–7.32(m,2H),7.24(d,J=7.6Hz ,1H),7.17(d,J=9.2Hz,1H),7.13(d,J=7.6Hz,1H),7.03–6.98(m,4H),5.86(d,J=8.8Hz,1H),1.27(s,9H). 13 C NMR (101MHz, CDCl3) δ162.2,150.4,150.1,149.2,145.3,144.9,139.4,139 .2,138.8,135.8(2C),133.3,132.8,130.4(2C),129.5,129.2,128.9,128.5 ,128.4,128.2,127.8,127.2,127.1,126.7,126.6,126.1,125.7,125.5,12 5.2,125.0,124.7(2C),122.9,119.9,112.9,34.4,31.5.HRMS(ESI-TOF)m / z Calcd.for C 42 H 33 N2O + [M+H] + :581.2587; Found:581.2590.

[0095] Example 6:

[0096]

[0097] The preparation method is the same as in Example 1. The product is a white solid, 368 mg, with a yield of 31%. 1H NMR (400MHz, CDCl3) δ9.01 (dd, J=4.0, 1.6Hz, 1H), 8.07 (dd, J=8.0, 2.0Hz, 1H), 7.93 (d, J=8.4Hz, 1H ),7.86(t,J=8.4Hz,2H),7.83(d,J=8.8Hz,1H),7.61(d,J=8.8Hz,1H),7.59(d,J=8.8Hz,1H),7.55( d,J=8.8Hz,1H),7.51(d,J=8.8Hz,1H),7.46–7.42(m,3H),7.39(d,J=8.8Hz,2H),7.36–7.31(m,3H) ,7.30–7.29(m,1H),7.28–7.26(m,2H),7.22–7.17(m,3H),7.14–7.09(m,3H),6.06(d,J=8.8Hz,1H). 13 C NMR (101MHz, CDCl3) δ162.1,150.3,150.0,145.2,144.9,141.1,140.6,139.2, 138.9(2C),135.8,135.5,133.3,132.9,130.6,130.5,129.9,129.6,128.9,128 .8,128.6,128.3,128.2,127.8,127.2(2C),127.1,126.8,126.6(2C),126.3,1 26.2,125.7(2C),125.2,125.1,124.6,122.8,120.2,112.7,HRMS(ESI-TOF)m / z Calcd.forC 44 H 29 N2O + [M+H] + :601.2274; Found:601.2267.

[0098] Example 7:

[0099]

[0100] The preparation method is the same as in Example 1, yielding a yellow solid, 640 mg, with a yield of 59%. 1H NMR (400MHz, CDCl3) δ9.03 (dd, J=4.4, 1.6Hz, 1H), 8.10 (dd, J=8.0, 2.0Hz, 1H), 7.93 (d, J=8.4Hz, 1H),7.89(d,J=7.6Hz,1H),7.85(d,J=8.4Hz,1H),7.84(d,J=8.8Hz,1H),7.76(d,J=8.8Hz,1H),7. 62–7.56(m,3H),7.47(dd,J=8.0,4.0Hz,1H),7.45–7.41(m,2H),7.36–7.30(m,3H),7.22(d,J=8.8 Hz,1H),7.11(ddd,J=8.4,6.8,1.6Hz,1H),6.92–6.85(m,4H),5.98(d,J=8.8Hz,1H),1.92(s,3H). 13 C NMR (101MHz, CDCl3) δ162.3,150.3,150.1,145.3,144.9,142.1,139.8,138.9 ,137.4,135.9,135.7,133.3,132.9,130.6(2C),130.6,129.5,128.9,128.4,1 28.3,128.2,127.8,127.5,127.3,127.1(2C),126.9,126.7,126.4,126.1,125 .8,125.6,125.3,125.1,124.7,122.9,120.2,112.9,21.2.HRMS(ESI-TOF)m / z Calcd.forC 39 H 27 N2O + [M+H] + :539.2118; Found:539.2115.

[0101] Example 8:

[0102]

[0103] The preparation method is the same as in Example 1, yielding a yellow solid of 321 mg and a yield of 33%. 1H NMR(400MHz, CDCl3)δ9.03(dd,J=4.4,1.6Hz,1H),8.17–8.14(m,1H),7.93(t,J=8.8Hz,2H),7.86(d,J=8.4 Hz,1H),7.85(d,J=9.2Hz,1H),7.74(d,J=8.8Hz,1H),7.63–7.60(m,3H),7.54–7.50(m,1H),7.49–7.45(m, 2H),7.38(dd,J=8.4,6.0Hz,1H),7.34(d,J=7.6Hz,1H),7.29(d,J=9.6Hz,1H),7.18–7.14(m,2H),7.11–7. 09(m,1H),7.01–7.00(m,1H),6.97(d,J=7.6Hz,1H),6.95–6.92(m,1H),5.80(d,J=8.8Hz,1H),0.81(s,9H). 13 C NMR (101MHz, CDCl3) δ162.4,150.3,150.1,145.4,144.9,141.6,139.9,139. 0,136.0,135.9,133.4,132.9,130.8,130.6,129.4,128.9,128.5,128.3(2C ),128.0,127.8,127.3,127.2,127.0,126.8(2C),126.2,125.8,125.6,125. 3,125.1,124.7,123.2,122.9,120.3,113.0,34.3,31.0.HRMS(ESI-TOF)m / z Calcd.for C 42 H 33 N2O + [M+H] + :581.2587; Found:581.2596.

[0104] Example 9:

[0105]

[0106] The preparation method is the same as in Example 1, yielding a yellow solid of 232 mg and a yield of 31%. 1H NMR (400MHz, CDCl3) δ9.04(d,J=3.6Hz,1H),8.13(d,J=8.4Hz,1H),7.98(t,J=8.8Hz, 2H),7.89(d,J=7.2Hz,2H),7.62(d,J=8.4Hz,2H),7.57(d,J=8.8Hz,1H),7.54–7.48(m ,4H),7.41–7.34(m,4H),7.29(s,1H),7.21(d,J=9.2Hz,1H),7.18–7.15(m,2H),7.11 (d,J=7.6Hz,2H),7.08(d,J=6.4Hz,2H),6.82(d,J=7.6Hz,2H),5.90(d,J=8.8Hz,1H). 13 CNMR (101MHz, CDCl3) δ162.1,150.3,150.0,145.3,144.9,142.5,140.4,140.2,139. 4,139.1,135.9,135.8,133.3,133.0,130.8,130.6,129.6,128.8,128.6,128.6,128 .4,128.4,128.3,128.2,128.0,127.8,127.4,127.2,127.0,126.8,126.7(2C),126. 3,125.8,125.7,125.3,125.2,124.8,124.6,122.8,120.2,112.6.HRMS(ESI-TOF)m / z Calcd.for C 44 H 29 N2O + [M+H] + :601.2274; Found:601.2265.

[0107] Example 10:

[0108]

[0109] The preparation method is the same as in Example 1, yielding a yellow solid of 281 mg and a yield of 43%. 1H NMR (400MHz, CDCl3) δ9.04 (dd, J=4.4, 1.6Hz, 1H), 8.11 (dd, J=8.0, 1.6Hz, 1H), 7.92 (d, J=8. 4Hz,1H),7.90–7.82(m,3H),7.77(d,J=8.4Hz,1H),7.63–7.55(m,3H),7.48(dd,J=8.4,4.4Hz ,1H),7.46–7.42(m,2H),7.38–7.34(m,2H),7.31(d,J=8.4Hz,1H),7.20(d,J=8.8Hz,1H),7.1 4(ddd,J=8.4,6.8,1.6Hz,1H),6.73(s,1H),6.63(s,2H),5.91(d,J=8.8Hz,1H),1.89(s,6H). 13 CNMR(101MHz,CDCl3)δ162.4,150.2,150.1,145.4,145.0,142.0,139.8,1 38.7,137.0,135.9,133.4,132.9,130.6,130.5,129.4,128.9,128.4,128. 3,128.2,128.1,127.9,127.8,127.54,127.3,127.0(2C),126.8,126.2,1 25.8,125.6,125.3,125.1,124.7,122.9,120.1,112.9.HRMS(ESI-TOF)m / z Calcd.for C 40 H 29 N2O + [M+H] + :553.2274; Found:553.2267.

[0110] Example 11:

[0111]

[0112] The preparation method is the same as in Example 1, yielding a yellow solid, 75 mg, with a yield of 17%. 1H NMR (400MHz, CDCl3) δ9.08(dd,J=4.4,1.6Hz,1H),8.20(dd,J=8.0,1.6Hz,1H),7.94(d,J=8.4Hz,2H),7.91(d ,J=8.0Hz,1H),7.84(d,J=8.4Hz,1H),7.77(d,J=9.2Hz,1H),7.73–7.69(m,2H),7.55(dd,J=8.0,4.4Hz,1H), 7.42(ddd,J=8.4,6.8,1.2Hz,1H),7.39–7.35(m,2H),7.25(s,1H),7.22–7.21(m,2H),7.17–7.15(m,1H),7.1 3–7.10(m,1H),6.58(s,1H),6.44(s,1H),6.31(dd,J=8.8,4.0Hz,1H),2.20(s,3H),1.73(s,3H),1.65(s,3H). 13 C NMR (101MHz, CDCl3) δ161.8,150.9,150.3,145.5,145.1,139.3,138.6,138.3 ,137.9,136.3,135.9,135.6,134.4,134.1,132.7,132.0,130.6,129.5,129.5 ,129.0(2C),128.2,128.0,127.9,127.8,127.7,127.6,126.1,126.0,125.9,1 25.7,125.1,124.7,123.0,119.2,114.7,21.6,21.3,21.0.HRMS(ESI-TOF)m / z Calcd.for C 41 H 31 N2O + [M+H] + :567.2431; Found:567.2425.

[0113] Example 12:

[0114]

[0115] The preparation method is the same as in Example 1, yielding a yellow solid of 389 mg and a yield of 40%. 1H NMR (400MHz, CDCl3) δ9.03(dd,J=4.4,2.0Hz,1H),8.14(dd,J=8.0,1.6Hz,1H),7.97(d,J=8.4Hz,1H),7.93(d,J=7.6Hz ,1H),7.88(d,J=8.0Hz,1H),7.85(d,J=8.8Hz,1H),7.68(dd,J=8.8,1.6Hz,2H),7.62(d,J=8.4Hz,1H),7.59(d,J=8.8H z,1H),7.51(dd,J=8.0,4.0Hz,1H),7.49–7.45(m,2H),7.41–7.35(m,2H),7.28(d,J=8.0Hz,1H),7.22(t,J=2.0Hz,1H) ,7.14(ddd,J=8.8,6.8,1.2Hz,1H),7.12(d,J=8.8Hz,1H),6.93(d,J=2.0Hz,2H),5.67(d,J=8.8Hz,1H),0.91(s,18H). 13 C NMR (101MHz, CDCl3) δ162.5,150.2,150.1(2C),145.3,144.9,140.8,139.9,139.1,136.1,135.8,133.5,132.8,130.8,130.5,129.3,128.8,12 8.5,128.4,128.3,127.7,127.3,127.0,126.8,126.1,125.6,125.1,12 4.8,124.2,122.9,120.2,120.0,112.9,34.6,31.2.HRMS(ESI-TOF)m / z Calcd.for C 46 H 41 N2O + [M+H] + :637.3213; Found:637.3207.

[0116] Example 13:

[0117]

[0118] The preparation method is the same as in Example 1. The product is a white solid, 236 mg, with a yield of 60%. 1H NMR (400MHz, CDCl3) δ9.05(d,J=4.0Hz,1H),8.12(d,J=8.4Hz,1H),8.07(d,J=8.4Hz,1H),7.99(d,J =8.4Hz,1H),7.93(t,J=7.2Hz,2H),7.68(s,1H),7.67(d,J=9.2Hz,1H),7.60(t,J=8.8Hz,2H),7.53 (d,J=9.2Hz,1H),7.49(dd,J=8.4,4.0Hz,1H),7.46–7.44(m,2H),7.42–7.40(m,2H),7.33(d,J=8.8 Hz,1H),7.34(s,2H),7.26(s,1H),7.25–7.14(m,7H),6.94(d,J=7.6Hz,4H),5.82(d,J=8.8Hz,1H). 13 C NMR (101MHz, CDCl3) δ162.0,150.1,150.0,145.2,144.8,142.9,140.9,140.3 ,139.2,139.1,136.2,135.7,133.4,133.0,130.9,130.7,129.7,128.8,128. 7,128.5,128.2,127.9,127.8,127.7,127.5,127.2,126.9(2C),126.8,126.4 ,125.9,125.7,125.2,124.4,123.4,122.8,120.2,112.1.HRMS(ESI-TOF)m / z Calcd.forC 50 H 33 N2O + [M+H] + :677.2587; Found:677.2581.

[0119] Example 14:

[0120]

[0121] The preparation method is the same as in Example 1, yielding a yellow solid, 91 mg, with a yield of 12%. 1H NMR (400MHz, CDCl3) δ9.04(dd,J=4.4,2.0Hz,1H),8.17(dd,J=8.4,2.0Hz,1H),8.09(d,J=8.0Hz,1H),7.98(d,J=8.8Hz,1H),7 .92(d,J=9.2Hz,2H),7.64–7.62(m,2H),7.61–7.60(m,1H),7.57(d,J=4.8Hz,1H),7.55(d,J=4.4Hz,1H),7.53(d,J=5.2Hz,1H) ,7.49(d,J=7.6Hz,1H),7.44(t,J=8.0Hz,1H),7.39(d,J=8.8Hz,1H),7.35(d,J=8.4Hz,1H),7.29(d,J=8.8Hz,1H),7.24–7.21 (m,1H),7.19(d,J=1.6Hz,2H),7.17(s,1H),7.15(d,J=8.4Hz,4H),6.84(d,J=8.4Hz,4H),5.76(d,J=8.4Hz,1H),1.31(s,18H). 13 C NMR (101MHz, CDCl3) δ162.2,150.3,150.1(2C),145.3,144.9,142.9,140.7,139 .5,139.4,137.5,136.3,135.9,133.5,133.1,131.0,130.8,129.8,128.9,128.8 ,128.3,128.0,127.8,127.3,127.2,127.1,127.0,126.6,126.5,125.9,125.5, 125.4,125.3,124.3,123.2,123.0,120.3,112.3,34.5,31.4.HRMS(ESI-TOF)m / z Calcd.for C 58 H 49 N2O + [M+H] + :789.3839;Found:789.3831.

[0122] Example 15:

[0123]

[0124] The preparation method is the same as in Example 1, yielding 30,428 mg of yellow solid, with a yield of 51%. 1H NMR (400MHz, CDCl3) δ8.10(d,J=8.4Hz,1H),7.92(t,J=8.0Hz,2H),7.88(d,J=9.2Hz, 1H),7.83(d,J=7.2Hz,1H),7.81(d,J=8.8Hz,1H),7.65(d,J=8.8Hz,1H),7.61(d,J=8 .8Hz,1H),7.56(d,J=8.4Hz,1H),7.52(d,J=8.4Hz,1H),7.45(ddd,J=8.0,5.6,2.0Hz ,1H),7.37–7.28(m,5H),7.14–7.06(m,4H),7.03–6.98(m,2H),6.18(d,J=8.8Hz,1H). 13 CNMR(101MHz, CDCl3)δ162.6,151.2,150.4,145.1,143.8,142.2,139.8,139.2,138.7,135.4,133.2,132.9,130.8,129.7,129.5,128.6,128.3, 127.8,127.7,127.3,127.0,126.9,126.7,126.5,126.3,126.2,125.8,125.7,125.2,124.3,124.0,120.6,113.7.HRMS(ESI-TOF)m / zCalcd.for C 38 H 24 ClN2O + [M+H] + :559.1572; Found:559.1578.

[0125] Example 16:

[0126]

[0127] The preparation method is the same as in Example 1, yielding 3p, 171mg of yellow solid, with a yield of 90%. 1H NMR (400MHz, CDCl3) δ8.15(d,J=8.4Hz,1H),8.05(d,J=8.4Hz,1H),7.99(d,J=9.2Hz,1H),7.91(t,J=7.2Hz,2H),7.87(s,2H), 7.83(d,J=8.8Hz,1H),7.72(d,J=7.6Hz,1H),7.70(d,J=8.8Hz,1H),7.62(d,J=8.4Hz,1H),7.59(d,J=8.8Hz,1H),7.56(d,J=8 .8Hz,1H),7.51(d,J=8.8Hz,1H),7.42(ddd,J=8.0,6.4,2.0Hz,1H),7.32–7.27(m,2H),7.23–7.20(m,2H),7.13(td,J=6.4,0. 8Hz,1H),7.02(s,1H),6.96–6.92(m,2H),6.89–6.85(m,1H),6.77(td,J=6.8,1.2Hz,1H),6.65(d,J=8.8Hz,1H),2.23(s,6H). 13 C NMR (101MHz, CDCl3) δ162.2,156.0,150.6,145.0,144.6,142.0,140.1,139.1, 139.0,138.2,136.4,134.9,133.2,132.6,131.1,131.0,129.2,129.1,128.3,1 28.1(2C),127.8,127.6,127.4,127.3,126.5(2C),126.4,125.8,125.5(2C),12 5.4,125.3,124.9,124.0,122.6,119.3,113.2,113.1,21.5.HRMS(ESI-TOF)m / z Calcd.for C 46 H 33 N2O + [M+H] + :629.2587; Found:629.2590.

[0128] Example 17:

[0129]

[0130] The preparation method is the same as in Example 1, yielding 3q,379mg of yellow solid with a yield of 56%. 1H NMR (400MHz, CDCl3) δ9.10(d,J=4.4Hz,1H),7.95(d,J=8.4Hz,1H),7.91(d,J=8.4Hz,1H),7.90(d,J=8.8Hz,1H),7.87(d,J=8.4Hz, 1H),7.71(s,2H),7.59(d,J=8.4Hz,1H),7.53–7.29(m,18H),7.12–7.08(m,3H),6.81(t,J=7.6Hz,2H),6.54(td,J=5.2,1.2Hz,1H). 13 C NMR (101MHz, CDCl3) δ161.9,151.8,150.7,149.6,148.3,145.9,145.8,141.8,139.8 ,138.1,137.7,135.6,133.3,132.9,130.7,130.5,129.7(2C),129.6,129.4,128.7,1 28.6,128.5(2C),128.3(2C),127.8,127.5,127.3,127.1,126.9,126.6,126.5,126. 4,126.1,125.6,125.1,123.7,123.5,123.4,122.3,120.0,113.4.HRMS(ESI-TOF)m / z Calcd.for C 50 H 33 N2O + [M+H] + :677.2587; Found:677.2588.

[0131] Example 18:

[0132]

[0133] The preparation method is the same as in Example 1, yielding 3r, 139mg of yellow solid, with a yield of 60%. 1H NMR (400MHz, CDCl3) δ9.01 (dd, J=4.4, 1.6Hz, 1H), 8.06 (dd, J=8.0, 2.0Hz, 1H), 8.03 (d, J=8.8Hz, 1H), 7.96 (d, J= 8.0Hz,1H),7.84(d,J=8.4Hz,1H),7.73(d,J=8.4Hz,1H),7.72(d,J=8.4Hz,1H),7.59(d,J=8.8Hz,1H),7.50(s,2 H),7.45(dd,J=8.0,4.4Hz,1H),7.44(td,J=6.8,2.0Hz,1H),7.35(d,J=8.4Hz,1H),7.34(d,J=8.4Hz,1H),7.27( td,J=6.8,1.2Hz,1H),7.22–7.18(m,2H),7.02(ddd,J=8.4,6.8,1.2Hz,1H),6.84(d,J=8.8Hz,1H),2.20(s,3H). 13 CNMR(101MHz, CDCl3)δ162.5,150.5,149.9,145.1,144.7,139.3,135.8,135.6,134.0,133.0,132.0,131.3,131.0,129.7,128.9,128.6,1 28.2,127.8,127.7,127.4,126.8,126.2,126.0,125.8,125.7,125.4,125.3,124.6,124.5,122.7,121.5,112.9,20.7.HRMS(ESI-TOF)m / z Calcd.for C 33 H 23 N2O + [M+H] + :463.1805; Found:463.1803.

[0134] Example 19:

[0135]

[0136] The preparation method is the same as in Example 1, yielding 3s, 96mg of yellow solid, with a yield of 11%. 1H NMR (400MHz, CDCl3) δ7.91(d,J=8.4Hz,1H),7.78(d,J=4.4Hz,1H),7.76(d,J=4.4 Hz,1H),7.72(d,J=8.4Hz,1H),7.58(d,J=2.8Hz,1H),7.55(d,J=3.2Hz,1H),7.45– 7.40(m,3H),7.35–7.33(m,3H),7.20(t,J=7.6Hz,1H),7.13(d,J=3.6Hz,1H),7.12 (d,J=2.4Hz,1H),6.88–6.85(m,3H),6.77(t,J=7.6Hz,1H),6.49(d,J=8.4Hz,1H). 13 C NMR (101MHz, CDCl3) δ161.4,150.3,143.5,142.0,140.1,138.8,134.6,133.1,132.6,131.1,130.7,129.1,129.0,128.4, 128.2,127.5,127.4,126.5,126.4,126.3,126.0,125.6,125.5,124.8,123.7,121.6,113.3.HRMS(ESI-TOF)m / zCalcd.for C 64 H 41 N2O2 + [M+H] + :869.3163; Found:869.3157.

[0137] Example 20: Optimization of synthetic conditions for 1,1'-biphenyl-2'-iodo-2-amide compounds (screening of copper salts)

[0138]

[0139]

[0140]

[0141] Unless otherwise stated, the reaction is carried out in 3 mL of dichloromethane solvent at a scale of 0.1 mmol.

[0142] Example 21: Optimization of synthetic conditions for 1,1'-biphenyl-2'-iodo-2-amide compounds (solvent screening)

[0143]

[0144]

[0145] Unless otherwise stated, the reaction is carried out in 3 mL of solvent at a scale of 0.1 mmol.

[0146] Example 22: Optimization of synthetic conditions for 1,1'-biphenyl-2'-iodo-2-amide compounds (base screening)

[0147]

[0148]

[0149] Unless otherwise stated, the reaction is carried out in 3 mL of dichloromethane solvent at a scale of 0.1 mmol.

[0150] Example 23: Optimization of synthetic conditions for 1,1'-biphenyl-2'-iodo-2-amide compounds (ligand screening)

[0151]

[0152]

[0153]

[0154] Unless otherwise stated, the reaction is carried out in 3 mL of dichloromethane solvent at a scale of 0.1 mmol.

[0155] Example 24: Asymmetric amination of cyclic diaryliodonium salts containing different substituents to synthesize diverse substituted 1,1'-biphenyl-2'-iodo-2-amide compounds

[0156]

[0157] A dry 25 mL Schlenk tube was used. Substrate 4 (0.1 mmol), copper acetate (10 mol%), and ligand 3m (12 mol%) were added. The gas was purged three times (under nitrogen atmosphere). Then, 3 mL of freshly distilled dichloromethane solvent was added, and the mixture was stirred at room temperature for 10 minutes to ensure homogeneity. Substrate 5 (0.12 mmol) and potassium phosphate (0.2 mmol) were then added under nitrogen atmosphere. The reaction was then carried out in a 40°C oil bath with stirring for 12 hours. After the reaction was completed, the reaction solvent was removed under reduced pressure, and the residue was purified by column chromatography. The enantiomeric ratio (er) of the product was analyzed by high performance liquid chromatography. The experimental results of the obtained 1,1'-biphenyl-2'-iodo-2-amide compounds with various substituents are shown in the table below.

[0158]

[0159]

[0160]

[0161]

[0162] Example 62: Optimization of synthetic conditions for 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters (screening of copper salts)

[0163]

[0164]

[0165] Unless otherwise stated, the reaction is carried out in 3 mL of dichloromethane solvent at a scale of 0.1 mmol.

[0166] Example 63: Optimization of synthetic conditions for 1,1'-biphenyl-2'-iodine-2-carboxylic acid esters (solvent screening)

[0167]

[0168]

[0169]

[0170] Unless otherwise stated, the reaction is carried out in 3 mL of dichloromethane solvent at a scale of 0.1 mmol.

[0171] Example 64: Optimization of synthetic conditions for 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters (ligand screening)

[0172]

[0173]

[0174]

[0175] Unless otherwise stated, the reaction is carried out in 3 mL of dichloromethane solvent at a scale of 0.1 mmol.

[0176] Example 65: Synthesis of diverse substituted 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters by asymmetric acyloxidation of cyclic diaryliodonium salts containing different substituents.

[0177]

[0178] A dry 25 mL Schlenk tube was used. Copper sulfate (5 mol%) and ligand 3 M (6 mol%) were added, and the gas was purged three times (under nitrogen atmosphere). Then, 3 mL of ultra-dry 1,2-dichloroethane was added, and the mixture was stirred at room temperature for 20 minutes to ensure homogeneity. Substrate 4 (0.1 mmol), 7 (0.12 mmol), and potassium phosphate (0.3 mmol) were then added under nitrogen atmosphere. The reaction was then stirred in a 40°C oil bath for 12 hours. After the reaction was completed, the reaction solvent was removed under reduced pressure, and the residue was purified by column chromatography. The enantiomeric ratio (er) of the product was analyzed by high performance liquid chromatography. The experimental results of the obtained 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters with various substituents are shown in the table below.

[0179]

[0180]

[0181]

[0182]

[0183] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. An axially chiral phenanthroline ligand, characterized in that, The axially chiral phenanthroline ligand is shown in the following general formula (Ⅰ): In general formula (Ⅰ): The B portion of the axially chiral phenanthroline ligand is any one of hydrogen atom, halogen, phenyl, substituted phenyl or the same as A; The axial chirality marked with * indicates either R-configuration or S-configuration; R 1 Selected independently from C 1-6 Any one of alkyl, phenyl, and substituted phenyl groups; R 2 and R 3 Each is independently selected from hydrogen, phenyl, or substituted phenyl.

2. The axially chiral phenanthroline ligand according to claim 1, characterized in that, When the R 1 C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or hexyl; when the R 1 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group. When the R 2 -R 3 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group. When B is a substituted phenyl group, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group.

3. A method for preparing the axially chiral phenanthroline ligand as described in claim 1, characterized by the following steps: Compound 3 was prepared by reacting compound 1 and compound 2 in an organic solvent under an inert gas environment with the help of copper salt, ligand and base; Y in compound 2 1 Selected from chlorine, bromine, or iodine atoms; Y 2 Selected from hydrogen atom, phenyl, substituted phenyl, or with Y 1 same; In compound 3, B is any one of hydrogen atom, halogen, phenyl, substituted phenyl, or the same as A.

4. The method for preparing axially chiral phenanthroline ligands according to claim 3, characterized in that, The organic solvent is a solvent commonly used in the field of organic synthesis, and is one or more of methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and dimethyl sulfoxide; preferably dimethyl sulfoxide. The inert gas includes one or more of argon, helium, neon, and krypton; The base is selected from one of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, sodium phosphate, sodium methoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, calcium hydride, n-butyllithium, sec-butyllithium, tert-butyllithium, diisopropylaminolithium, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, and pyridine; The copper salt is one of the following: copper chloride, copper bromide, cuprous chloride, cuprous bromide, cuprous iodide, copper acetate, copper acetylacetone, copper perchlorate, copper trifluoroacetate, copper tetrafluoroborate, copper tetraacetonitrile hexafluorophosphate, cuprous cyanide, cuprous thiocyanate, cuprous thiophene-2-carboxylate, and cuprous oxide. The ligand is an oxalamide ligand; In the preparation method of the axially chiral phenanthroline ligand, the molar ratio of compound 1 to compound 2 is 1:5 to 5:

1.

5. A method for synthesizing axially chiral, multi-substituted 1,1'-biphenyl-2'-iodo-2-amide compounds, characterized in that, The method for synthesizing axially chiral, diversified substituted 1,1'-biphenyl-2'-iodo-2-amide compounds comprises the following steps: under an inert gas atmosphere, the axially chiral phenanthroline ligand as described in claim 1 is in situ complexed with a copper salt in an organic solvent to form a catalyst, followed by the addition of a base, and compounds 4 and 5 are reacted at a desired temperature and for a desired time to obtain compound 6. Among them, R 4 -R 11 Selected from hydrogen, alkyl, phenyl, substituted phenyl, halogen, or naphthyl; R 12 Selected from alkyl, phenyl, substituted phenyl, heteroaryl, or naphthyl; The chiral axis marked with * is either S-configuration or R-configuration.

6. The method for synthesizing diverse substituted 1,1'-biphenyl-2'-iodo-2-amide compounds according to claim 5, characterized in that, When the R 4 -R 11 When R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl; 4 -R 11 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group. When the R 12 When R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl; 12 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group; when the R 12 When the heteroaryl group is a furanyl, thiophene, indolyl, or pyridinyl group; The organic solvent is a solvent commonly used in the field of organic synthesis, including one or more of methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, or dimethyl sulfoxide; preferably dichloromethane. The inert gas includes one or more of argon, helium, neon, and krypton; The copper salt is one of the following: copper chloride, copper bromide, cuprous chloride, cuprous bromide, cuprous iodide, copper acetate, copper acetylacetone, copper perchlorate, copper trifluoroacetate, copper tetrafluoroborate, copper tetraacetonitrile hexafluorophosphate, cuprous cyanide, cuprous thiocyanate, cuprous thiophene-2-carboxylate, and cuprous oxide. The base is one of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium phosphate, sodium phosphate, cesium carbonate, sodium methoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, calcium hydride, n-butyllithium, sec-butyllithium, tert-butyllithium, diisopropylaminolithium, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, or pyridine; The molar concentrations of compounds 4 and 5 in the organic solvent are 0.01–5.0 M; The molar ratio of compound 4 to the base is 10:1 to 1:10; The molar ratio of the copper salt to the axially chiral phenanthroline ligand is 1:5 to 5:1; The reaction temperature is -50 to 50°C; The reaction time is 1 to 180 hours.

7. A method for synthesizing axially chiral, multi-substituted 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters, characterized in that, The method for synthesizing axially chiral, multi-substituted 1,1'-biphenyl-2'-iodo-2-carboxylic acid esters comprises the following steps: under an inert gas atmosphere, the axially chiral phenanthroline ligand as described in claim 1 is in situ complexed with a copper salt in an organic solvent to form a catalyst, followed by the addition of a base, and compounds 4 and 7 are reacted at a desired temperature and for a desired time to obtain compound 8; Among them, R 4 -R 11 Selected from hydrogen, alkyl, phenyl, substituted phenyl, halogen, or naphthyl; R 13 Selected from alkyl, phenyl, substituted phenyl, heteroaryl, or naphthyl; The chiral axis marked with * is either S-configuration or R-configuration.

8. The method for synthesizing diverse substituted 1,1'-biphenyl-2'-iodine-2-carboxylic acid esters according to claim 7, characterized in that, When the R 4 -R 11 When R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl; 4 -R 11 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group. When the R 13 When R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl; 13 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group; when the R 13 When the heteroaryl group is a furanyl, thiophenyl, indolyl, quinolinyl, isoquinolinyl, pyrroleyl, or pyridyl; The organic solvent is a solvent commonly used in the field of organic synthesis, including one or more of methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, or dimethyl sulfoxide; preferably 1,2-dichloroethane. The inert gas includes one or more of argon, helium, neon, and krypton; The copper salt is one of the following: copper chloride, copper bromide, cuprous chloride, cuprous bromide, cuprous iodide, copper acetate, copper acetylacetone, copper perchlorate, copper trifluoroacetate, copper tetrafluoroborate, copper tetraacetonitrile hexafluorophosphate, cuprous cyanide, cuprous thiocyanate, cuprous thiophene-2-carboxylate, and cuprous oxide. The base is one of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium phosphate, sodium phosphate, cesium carbonate, sodium methoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, calcium hydride, n-butyllithium, sec-butyllithium, tert-butyllithium, diisopropylaminolithium, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, or pyridine; The molar concentrations of compounds 4 and 7 in the organic solvent are 0.01–5.0 M; The molar ratio of compound 4 to the base is 10:1 to 1:10; The molar ratio of the copper salt to the axially chiral phenanthroline ligand is 1:5 to 5:1; The reaction temperature is -50 to 50°C; The reaction time is 1 to 180 hours.

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