Aryl iodine containing axial chirality and central chirality, preparation method and use thereof

Abstract

The present invention discloses an aryl iodine catalyst containing axial chirality and central chirality, a preparation method and use thereof, and an application thereof in the α-position sulfonyloxylation reaction of propiophenone and its derivatives. The aryl iodine catalyst containing axial chirality and central chirality has a structure of the general formula (I). The aryl iodine catalyst containing axial chirality and central chirality provided by the present invention catalyzes the α-position sulfonyloxylation asymmetric synthesis reaction of propiophenone and its derivatives under the co-oxidation effect of an oxidant, exhibits good yield, good to excellent enantioselectivity and good reaction substrate universality, and has good industrial application prospects. The present invention belongs to the field of asymmetric synthetic chemistry.

Description

Technical Field

[0001] The invention belongs to the field of asymmetric synthetic chemistry, and specifically relates to a novel aryl iodide catalyst containing both an axial chiral binaphthyl structure and a central chiral structure, a preparation method and use thereof. The catalyst can be used for the α-position asymmetric sulfonyloxylation reaction of propiophenone and its derivatives, and has high catalytic activity and enantioselectivity. Background Art

[0002] Axially chiral biaryl compounds are not only widely present in natural products and drug molecules, but are also often used as chiral sources in the design and development of chiral catalysts, playing an important role in the field of asymmetric synthesis. Since Noyori et al. pioneered the development of binaphthylbisphosphine ligands (BINAP), new biaryl axial chiral ligands have been continuously developed and widely used in transition metal-catalyzed asymmetric synthesis reactions. (Noyori, R. et al. J. Am. Chem. Soc. 1979, 101, 3129-3131; Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029-3070; Yudin, AK et al. Chem. Rev. 2003, 103, 3155-3212; Brunel, JM Chem. Rev. 2005, 105, 857–897.). Among metal-free organic small molecule catalysts, chiral aryl iodide catalysts have been rapidly developed in recent years due to their low toxicity, insensitivity to oxygen and moisture in the air, simple use, easy handling and recycling, and other advantages. They have high application value in the synthesis of chiral molecules. In 2007, Wirth's group first applied chiral aryl iodide catalysts to the α-sulfonyloxylation reaction of phenylacetone, which achieved good to excellent yields. However, after screening a series of chiral aryl iodide catalysts, the highest ee value was still only 28%. Since then, many chemists have conducted extensive and in-depth research on this reaction. For example, in 2011, Zhang's group designed and synthesized a class of chiral aryl iodide catalysts derived from spirodihydroindane skeletons, obtained the corresponding products with moderate to good yields, and increased the enantioselectivity of the reaction to 58% (ee value). In 2020, the Nachtsheim research group designed and synthesized a type of chiral aryl iodide catalyst containing a triazole unit to catalyze the reaction, and obtained the final product with excellent yield and an ee value of up to 88%. The enantioselectivity needs to be improved, and the substrate applicability is not good. Neither the chiral aryl iodide catalysts reported domestically or internationally for the α-sulfonyloxylation of phenylacetone have ever achieved an enantioselectivity (ee value) of more than 90%, and the optical purity of the obtained product still cannot meet the needs of various fields for this type of chiral product. Therefore, the design and development of new chiral aryl iodide catalysts with high enantioselectivity not only has important theoretical research significance, but also has high application value in the synthesis of related chiral products.(Wirth, T. et al. Synlett 2007, 2007, 538-542; Yu, J. et al. Tetrahedron: Asymmetry 2011, 22, 2039-2055; Abazid, AH; Nachtsheim, BJ Angew. Chem. Int. Ed. 2020, 59, 1479-1484.). Summary of the invention

[0003] The purpose of the present invention is to provide a novel aryl iodide catalyst containing both an axial chiral binaphthyl structure and a central chiral structure.

[0004] Another object of the present invention is to provide a method for synthesizing the chiral aryl iodide catalyst.

[0005] The present invention also aims to provide the use of the chiral catalyst, namely, for the asymmetric sulfonyloxylation reaction of α-position of propiophenone and its derivatives.

[0006] The present invention provides a chiral aryl iodide catalyst containing both an axial chiral binaphthyl structure and a central chiral structure, characterized in that the chiral aryl iodide catalyst has a structure shown in general formula (I):

[0007]

[0008] In the general formula (I):

[0009] R 1 Selected from C 1-6 Any of alkyl, cycloalkyl, aryl, heteroaryl, and arylmethyl;

[0010] R 2 -R 7 are independently selected from hydrogen, halogen, C 1-6 Any one of an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, a nitro group, an ester group, a cyano group, an aldehyde group, a silyl-oxy group and a silyl-oxy group;

[0011] R 8 Selected from hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heteroaryl, C 1-6 Silane, silanyl, C 1-6 Any of alkyl acyl and aryl acyl;

[0012] The axial chirality marked with * is R configuration or S configuration, or racemic;

[0013] In a preferred experimental scheme of the present invention, when the R 1 C 1-6 When the C1-6 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 R is a cycloalkyl group, the cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group or a cyclooctyl group; 1 When R is an aryl group, the aryl group is phenyl, methyl substituted phenyl, ethyl substituted phenyl, isopropyl substituted phenyl, tert-butyl substituted phenyl, neopentyl substituted phenyl, adamantyl substituted phenyl, trifluoromethyl substituted phenyl, methoxy substituted phenyl, ethoxy substituted phenyl, tert-butyloxy substituted phenyl, fluorine substituted phenyl, chlorine substituted phenyl, bromine substituted phenyl, iodine substituted phenyl, naphthyl, anthracenyl, phenanthryl or pyrenyl; when R 1 When R is a heteroaryl group, the heteroaryl group is furyl, thienyl, indolyl or pyridyl; 1 When it is an arylmethyl group, the arylmethyl group is benzyl, methyl-substituted benzyl, ethyl-substituted benzyl, isopropyl-substituted benzyl, tert-butyl-substituted benzyl, neopentyl-substituted benzyl, adamantyl-substituted benzyl, trifluoromethyl-substituted benzyl, methoxy-substituted benzyl, ethoxy-substituted benzyl, tert-butyloxy-substituted benzyl, fluorine-substituted benzyl, chlorine-substituted benzyl, bromine-substituted benzyl, naphthylmethyl, anthracenemethyl, phenanthrylmethyl or pyrenemethyl;

[0014] In a preferred experimental scheme of the present invention, when the R 2 -R 7 C 1-6 When 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 2 -R 7 When each of R is independently a cycloalkyl, the cycloalkyl is a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl group; when R 2 -R 7 When they are independently alkyl-oxy, the alkyloxy is methoxy, ethoxy, n-propoxy, isopropoxy, n-butyloxy, isobutyloxy or tert-butyloxy; when the R 2 -R 7When they are independently aryl, the aryl is phenyl, methyl substituted phenyl, ethyl substituted phenyl, isopropyl substituted phenyl, tert-butyl substituted phenyl, neopentyl substituted phenyl, adamantyl substituted phenyl, trifluoromethyl substituted phenyl, methoxy substituted phenyl, ethoxy substituted phenyl, tert-butyloxy substituted phenyl, fluorine substituted phenyl, chlorine substituted phenyl, bromine substituted phenyl, naphthyl, anthracenyl, phenanthryl or pyrene; when the R 2 -R 7 When they are independently heteroaryl, the heteroaryl is furyl, thienyl, indolyl or pyridyl;

[0015] In a preferred experimental scheme of the present invention, when the R 8 C 1-6 When 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 8 When R is a cycloalkyl group, the cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group or a cyclooctyl group; 8 When R is an aryl group, the aryl group is phenyl, methyl substituted phenyl, ethyl substituted phenyl, isopropyl substituted phenyl, tert-butyl substituted phenyl, neopentyl substituted phenyl, adamantyl substituted phenyl, trifluoromethyl substituted phenyl, methoxy substituted phenyl, ethoxy substituted phenyl, tert-butyloxy substituted phenyl, fluorine substituted phenyl, chlorine substituted phenyl, bromine substituted phenyl, naphthyl, anthracenyl, phenanthryl or pyrenyl; when R 8 When R is a heteroaryl group, the heteroaryl group is furyl, thienyl, indolyl, pyridyl or quinolyl; 8 C 1-6 When the silyl group is methylsilyl, ethylsilyl, n-propylsilyl, isopropylsilyl, n-butylsilyl, isobutylsilyl, n-pentylsilyl, isopentylsilyl, neopentylsilyl or hexylsilyl; when the R 8 When R is a silyl group, the silyl group is a phenylsilyl group, a methyl-substituted phenylsilyl group, a trifluoromethyl-substituted phenylsilyl group, a methoxy-substituted phenylsilyl group, a tert-butyl-substituted phenylsilyl group or a fluorine-substituted phenylsilyl group; when R 8 C 1-6 When the C 1-6 The alkyl acyl group is methyl acyl, ethyl acyl, n-propyl acyl, isopropyl acyl, n-butyl acyl, isobutyl acyl, n-pentyl acyl, isopentyl acyl, neopentyl acyl or hexyl acyl; when the R 8When it is an aryl acyl group, the aryl acyl group is phenyl acyl, methyl substituted phenyl acyl, ethyl substituted phenyl acyl, isopropyl substituted phenyl acyl, tert-butyl substituted phenyl acyl, neopentyl substituted phenyl acyl, adamantyl substituted phenyl acyl, trifluoromethyl substituted phenyl acyl, methoxy substituted phenyl acyl, ethoxy substituted phenyl acyl, tert-butyloxy substituted phenyl acyl, fluorine substituted phenyl acyl, chlorine substituted phenyl acyl, bromine substituted phenyl acyl, naphthyl acyl, anthryl acyl, phenanthryl acyl or pyrenyl acyl;

[0016] Preparation of aryl iodide catalysts containing axial chirality and central chirality of general formula (I): an aryl iodine compound of structural formula a and a binaphthyl axial chiral compound b are dissolved in an organic solvent, reacted at 0 to 150° C. for 1 to 60 hours under the action of a condensing agent to obtain an intermediate c, and the intermediate c is then reacted with a compound d under the action of a base to finally obtain a product 1:

[0017]

[0018] X in the compound a is selected from a hydroxyl group or an amine group;

[0019] In the present invention, the organic solvent is a solvent conventionally used in the field of organic synthesis, and the organic solvent is one or more of methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 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 dichloromethane.

[0020] In the present invention, the condensing agent is at least selected from dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), O-benzotriazole-tetramethyluronium hexafluorophosphate (HBTU), 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU), O-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroborate one of (TBTU), 2-succinimidyl-1,1,3,3-tetramethyluronium tetrafluoroborate (TSTU), 2-(endo-5-norbornene-2,3-dicarboximido)-1,1,3,3-tetramethyluronium tetrafluoroborate (TNTU), benzotriazol-1-oxytris(dimethylamino)phosphine hexafluorophosphate (BOP), benzotriazol-1-yl-oxytripyrrolidinylphosphine hexafluorophosphate (PyBOP), and (3H-1,2,3-triazolo[4,5-b]pyridine-3-oxy)tris-1-pyrrolidinylphosphine hexafluorophosphate (PyAOP);

[0021] In the present invention, the reaction temperature is 0-150°C.

[0022] In the present invention, the reaction time is 1 to 60 hours.

[0023] In the present invention, the molar concentration of the reaction compound a in the organic solvent is 0.01 to 2 mol / L.

[0024] In the present invention, after the synthesis reaction is completed, decompression and desolventizing are also included.

[0025] In the present invention, after the synthesis reaction is completed, a post-processing step is further 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 of extraction, washing, drying, and column chromatography.

[0026] In the present invention, the extractant can be a conventional extractant in the field of organic synthesis, including ethyl acetate, dichloromethane, chloroform, and ether. The washing solution can be a conventional washing solution in the field, such as a saturated sodium chloride solution; the drying can use a conventional drying agent in the field, such as anhydrous sodium sulfate and anhydrous magnesium sulfate; the column chromatography can be a 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 petroleum ether, dichloromethane, ethyl acetate or methanol.

[0027] The present invention also provides a method for synthesizing α-sulfonyloxypropiophenone and its derivatives, comprising the following steps: under certain temperature and reaction gas conditions, using aryl iodine containing axial chirality and central chirality as a catalyst, and under the action of an external oxidant, compound 2 and compound 3 are reacted in an organic solvent to obtain compound 4 according to the following formula:

[0028]

[0029] Among them, R 9 -R 13 are independently alkyl, aryl, heteroaryl, carboxyl, ester, aldehyde, acyl, amine, halogen or nitro; R 14-15 is selected from alkyl, aryl, heteroaryl;

[0030] The chiral axes marked with * are S or R configuration or racemic.

[0031] In the present invention, when the R 9 -R 13 When any one of is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl or cyclohexyl;

[0032] In the present invention, when the R 9 -R 13 When any one of them is an aryl group, the aryl group is phenyl, methyl-substituted phenyl, ethyl-substituted phenyl, isopropyl-substituted phenyl, tert-butyl-substituted phenyl, neopentyl-substituted phenyl, adamantyl-substituted phenyl, trifluoromethyl-substituted phenyl, methoxy-substituted phenyl, ethoxy-substituted phenyl, tert-butyloxy-substituted phenyl, fluorine-substituted phenyl, chlorine-substituted phenyl, bromine-substituted phenyl, naphthyl, anthracenyl, phenanthryl or pyrene;

[0033] In the present invention, when the R 9 -R 13 When any one of the heteroaryl groups is selected from , the heteroaryl group is furanyl, thienyl, indolyl or pyridyl;

[0034] In the present invention, when the R 14-15 When selected from alkyl, the alkyl is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl or cyclohexyl;

[0035] In the present invention, when the R 14-15When selected from aryl, the aryl is phenyl, methyl substituted phenyl, ethyl substituted phenyl, isopropyl substituted phenyl, tert-butyl substituted phenyl, neopentyl substituted phenyl, adamantyl substituted phenyl, trifluoromethyl substituted phenyl, methoxy substituted phenyl, ethoxy substituted phenyl, tert-butyloxy substituted phenyl, fluorine substituted phenyl, chlorine substituted phenyl, bromine substituted phenyl, naphthyl, anthracenyl, phenanthryl or pyrenyl;

[0036] In the present invention, when the R 14-15 When selected from heteroaryl, the heteroaryl is furyl, thienyl, indolyl or pyridyl;

[0037] In the present invention, the organic solvent is a solvent conventionally used in the field of organic synthesis, including methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, ether, ethyl acetate, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone or dimethyl sulfoxide; preferably ethyl acetate.

[0038] In the present invention, the reaction gas is nitrogen, oxygen, carbon monoxide, carbon dioxide or air.

[0039] In the present invention, the added oxidant is selected from at least one of oxygen, potassium permanganate, potassium dichromate, manganese dioxide, hydrogen peroxide, potassium chlorate, sodium hypochlorite, sodium persulfate, ammonium persulfate, peracetic acid, meta-chloroperbenzoic acid, sodium percarbonate, benzoyl peroxide, iron oxide, titanium oxide, copper oxide, aluminum oxide, calcium oxide, cobalt oxide, lead oxide, zinc oxide, magnesium oxide, vanadium oxide, phosphorus oxide, boron oxide, pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), etc.;

[0040] In the present invention, the molar concentration of the compound 2 and the compound 3 in the organic solvent is 0.01 to 2.0 M;

[0041] In the present invention, the molar ratio of the added oxidant to the aryl iodide catalyst 1 containing axial chirality and central chirality is 10:1 to 30:1;

[0042] In the present invention, the reaction temperature is -30 to 100°C;

[0043] In the present invention, the reaction time is 1 to 96 hours;

[0044] In an embodiment of the present invention, after the reaction is completed, a post-treatment step is further included. The post-treatment step can be a conventional post-treatment step in the field of organic synthesis, and the post-treatment step includes a column chromatography step.

[0045] The term "ee" refers to enantiomeric excess.

[0046] The positive and progressive effects of the present invention are:

[0047] The present invention provides a novel chiral aryl iodide catalyst containing both an axial chiral binaphthyl structure and a central chiral structure. The synthesis method of the catalyst uses an aryl iodide derivative with binaphthol and resorcinol as a core skeleton as a starting material, and a condensation reaction is carried out between the hydroxyl group on the binaphthyl skeleton and the aryl iodide derivative under the action of a condensing agent to construct a carbon heteroatom bond. The target molecular structure of the present invention is concise and clear, the experimental operation is simple, and it can be prepared on a large scale.

[0048] The novel aromatic iodide catalyst containing axial chirality and central chirality provided by the present invention can directly catalyze the α-sulfonyloxylation reaction of propiophenone and its derivatives, showing good yield (up to 88%) and good to excellent enantioselectivity (ee value up to 95%) and universality of reaction substrates, and has good industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 The H NMR spectrum of an aryl iodide catalyst 1a containing axial chirality and central chirality provided in an embodiment of the present invention;

[0050] Figure 2 The NMR carbon spectrum of an aryl iodide catalyst 1a containing axial chirality and central chirality provided in an embodiment of the present invention;

[0051] Figure 3 The H NMR spectrum of an aryl iodide catalyst 1b containing axial chirality and central chirality provided in an embodiment of the present invention;

[0052] Figure 4 The NMR carbon spectrum of an aromatic iodine catalyst 1b containing axial chirality and central chirality provided in an embodiment of the present invention;

[0053] Figure 5 The H NMR spectrum of an aryl iodide catalyst 1c containing axial chirality and central chirality provided in an embodiment of the present invention;

[0054] Figure 6 The NMR carbon spectrum of an aromatic iodine catalyst 1c containing axial chirality and central chirality provided in an embodiment of the present invention;

[0055] Figure 7 The H NMR spectrum of an aryl iodide catalyst 1d containing axial chirality and central chirality provided in an embodiment of the present invention;

[0056] Figure 8The NMR carbon spectrum of an aromatic iodine catalyst 1d containing axial chirality and central chirality provided in an embodiment of the present invention;

[0057] Fig. 9 The H NMR spectrum of an aryl iodide catalyst 1e containing axial chirality and central chirality provided in an embodiment of the present invention;

[0058] Fig.10 The NMR carbon spectrum of an aromatic iodide catalyst 1e containing axial chirality and central chirality provided in an embodiment of the present invention;

[0059] Fig.11 The hydrogen NMR spectrum of an aromatic iodine catalyst 1f containing axial chirality and central chirality provided in an embodiment of the present invention;

[0060] Fig.12 The NMR carbon spectrum of an aromatic iodine catalyst 1f containing axial chirality and central chirality provided in an embodiment of the present invention;

[0061] Fig.13 The H NMR spectrum of the product 4a of the α-sulfonyloxylation of propiophenone catalyzed by aryl iodide provided in an embodiment of the present invention;

[0062] Fig.14 The NMR carbon spectrum of the product 4a of the α-sulfonyloxylation of propiophenone catalyzed by aryl iodide provided in an embodiment of the present invention;

[0063] Fig.15 A single crystal structure diagram of an aryl iodide catalyst 1f containing axial chirality and central chirality provided in an embodiment of the present invention; DETAILED DESCRIPTION

[0064] The present invention is further described in detail below through specific examples, but the scope of the present invention is not limited thereby.

[0065] The information of the instruments and experimental materials used in the following examples are as follows:

[0066] All chemical reagents were purchased from commercial reagents from Adamas, Bidex Pharmaceuticals, J.B. & K. Wells, etc. Thin layer chromatography (TLC) used SHF254 silica gel plates, silica gel column chromatography used Nortec silica gel powder (300-400 mesh), and TLC used UV light (254 nm). 1 H NMR and 13 C NMR was characterized using a Bruker AVANCEⅢ 400 MHz NMR instrument and an Ascend 600 MHz NMR instrument, with deuterated chloroform as the solvent. The unit of chemical shift is ppm, and the unit of coupling constant is Hz. 1In HNMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, m represents multiplet, and br represents broad peak. 13 In C NMR, δ represents chemical shift. High-resolution mass spectrometry was performed using a JEOC AccuTOF LC-plus 4G instrument with an ESI ion source or a Waters GCT Premier with an EI ion source. Enantiomeric excess (ee) was determined using a Shimadzu LC-20A high-performance liquid chromatography and a Daicel Chiralpak chiral column.

[0067] Embodiment 1:

[0068]

[0069] Add 100mL of DCM solvent to a dry 100mL Schlenk bottle, dissolve in 400.1mg of dinaphthol (1.40mmol), compound a-1 (300mg, 0.56mmol) and DMAP (7.3mg, 0.06mmol), and then place in an ice-water bath and stir for 10 minutes. Dissolve a certain amount of DCC (231.1mg, 1.12mmol) in 5mL of DCM and slowly add it to the above reaction solution through a syringe and stir at room temperature for 12h. After the reaction is completed, quench the reaction with ice water and extract with dichloromethane (3×15mL). Wash the combined organic phase with saturated sodium chloride, dry it over anhydrous Na2SO4, remove the solvent under reduced pressure, and purify the residue by silica gel column chromatography using petroleum ether / ethyl acetate (5:1) as eluent to obtain white solid c-1 (368mg, yield 62%). Next, into another dry 50 mL Schlenk bottle, add the white solid c-1 (368 mg, 0.34 mmol), DMAP (4.0 mg, 0.03 mmol) and NaH (40.8 mg, 1.02 mmol) obtained in the previous step, replace the nitrogen in the reaction system three times and add anhydrous dichloromethane (10 mL) through a syringe under a nitrogen atmosphere, then place in an ice-water bath and stir for 10 minutes. Slowly add 2,4,6-trimethylbenzoyl chloride (248.4 mg, 1.36 mmol) dropwise into the reaction system at 0°C, and the reaction mixture is stirred at room temperature for 12 h. TLC was used to monitor whether the reaction was complete. After the raw material was completely converted, a small amount of ice water was added to quench the excess NaH, and then dichloromethane solvent was used for extraction (3×30 mL). The combined organic layer was washed with water for several times, and finally washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and part of the solvent was removed under reduced pressure. After purification by silica gel column chromatography (petroleum ether / ethyl acetate=10 / 1), a white solid 1a (407 mg, yield 88%) was obtained. 1H NMR (400MHz, CDCl3) δ7.90(d,J=8.8Hz,2H),7.86(d,J=8.4Hz,2H),7.71(d,J =7.6Hz,2H),7.61(d,J=8.4Hz,2H),7.48–7.30(m,6H),7.31–7.10(m,20H),6. 68(s,4H),6.40(t,J=7.6Hz,1H),5.79(d,J=7.6Hz,2H),4.55(d,J=8.4Hz,2H ),2.58(t,J=11.6Hz,2H),2.38(d,J=14.0Hz,2H),2.18(s,6H),1.81(s,12H). 13 C NMR (101MHz, CDCl3) δ168.7,168.5,157.2,147.0,146.2,139.6,136.4,135.5,133.5,133.3,131.8,131.4,130.0,129.9,129.8,129.7,129 .3,128.3,128.2,127.9,127.1,126.4,126.1,126.0,125.8,123.8,123.3,121.7,121.2,104.6,78.3,37.9,21.1,19.2.HRMS(ESI-TOF)m / z Calcd.for C 84 H 65 INaO 10 + [M+Na] + :1383.3515;Found:1383.3524.

[0070] Embodiment 2:

[0071]

[0072] The preparation method is the same as that of Example 1, white solid, 413 mg, two-step total yield 61%; 1H NMR (400MHz, CDCl3) δ8.03 (d, J = 8.8 Hz, 2H), 7.91 (d, J = 8.0 Hz, 2H), 7.90 (d, J = 9. 2Hz,2H),7.82(d,J=8.4Hz,2H),7.53(d,J=8.8Hz,2H),7.46–7.33(m,5H),7.32–7 .27(m,3H),7.26–7.20(m,6H),6.62(s,4H),6.39(t,J=8.2Hz,1H),5.57(d,J=8.0 Hz,2H),4.39(q,J=6.8Hz,2H),2.09(s,6H),1.84(s,12H),1.28(d,J=6.8Hz,6H). 13 C NMR (101MHz, CDCl3) δ169.6,168.4,157.6,147.2,146.4,139.6,135.6,133.5,133.4,131.8,131.5,130.0,129.8,129.5,129.4,128. 4,128.3,127.9,127.0,126.3,126.2,126.0(2C),123.9,123.6,121.9,121.4,106.4,80.2,73.6,21.0,19.3,18.0.HRMS(ESI-TOF)m / z Calcd.for C 72 H 57 INaO 10 + [M+Na] + :1231.2889;Found:1231.2909.

[0073] Embodiment 3:

[0074]

[0075] The preparation method is the same as that of Example 1, white solid, 429 mg, two-step total yield 49%; 1H NMR (400MHz, CDCl3) δ7.91(d,J=13.2Hz,6H),7.84(d,J=8.4Hz,2H),7.58–7.37(m,13H),7.36–7.25(m,5H),7.25–7.18(m,4H),7.18–6.99(m,1 1H),7.00–6.85(m,5H),6.60(s,4H),6.09(t,J=8.2Hz,1H),4.71(s,2H ),4.19(d,J=9.6Hz,2H),2.15(s,6H),2.07–1.57(m,4H),1.32(s,12H). 13 C NMR(151MHz,CDCl3)δ167.6,162.8(d,J C-F =247.6Hz),162.5(d,J C-F =243.1Hz),156.9,145.6,144.6,140.2,137.6,134.1,133.7,133.2,132.8,132.2,132.0 ,131.5,131.2,130.9,129.7,129.0,128.2,128.0,127.3,126.8,126.2,125.5,115.5(d,J C-F =19.6Hz),104.3,77.6,37.1,21.1,19.3. 19 F NMR(376MHz, CDCl3): δ-113.6,-114.3.HRMS(ESI-TOF)m / z Calcd.for C 108 H 77 IF4NaO 10 + [M+Na] + :1759.4390;Found:1759.4398.

[0076] Embodiment 4:

[0077]

[0078] The preparation method is the same as that of Example 1, white solid, 444 mg, two-step total yield 42%; 1H NMR (400MHz, CDCl3) δ7.94(s,2H),7.91–7.80(m,4H),7.71(s,2H),7.53–7.33(m,15H),7.33–7.15(m,14H),7.02(s,9H),6 .54(s,4H),5.98(t,J=7.6Hz,1H),4.96(s,2H),4.21(s,2H),2.35–2.15(m,4H),2.13(s,6H),1.30(s,12H),1.24(s,36H). 13 CNMR(151MHz,CDCl3)δ167.9,167.2,157.0,150.7,145.9,144.9,139.8,13 7.6,135.2,135.0,134.8,133.0,132.6,132.2,132.0,131.0,130.9,129.5 ,129.1,128.7,128.3,128.1,127.7,126.8,126.6(2C),126.4,126.3,125. 4,125.3(2C),104.8,78.1,37.5,34.6,31.5,21.1,19.4.HRMS(ESI-TOF)m / z Calcd.for C 124 H 113 INaO 10 + [M+Na] + :1911.7271;Found:1911.7270.

[0079] Embodiment 5:

[0080]

[0081] The preparation method is the same as that of Example 1, light yellow solid, 479 mg, two-step total yield 39%; 1 H NMR(400MHz, CDCl3)δ8.08(s,4H),8.04–7.96(m,4H),7.92(s,10H),7.77(s ,2H),7.57(t,J=7.0Hz,2H),7.54–7.41(m,6H),7.35(t,J=7.6Hz,2H),7.24 –7.00(m,12H),6.67(s,4H),5.89–5.67(m,1H),4.76(s,2H),4.30(d,J=10. 0Hz,2H),2.20(s,6H),2.15–2.03(m,2H),1.98–1.77(m,2H),1.47(s,12H). 13C NMR (151MHz, CDCl3) δ167.6,166.8,156.9,145.2,143.8,141.1,140.4,140 .0,137.8,136.1,133.7,133.2,132.4(2C),132.3,132.2,132.1(2C),132. 0,131.9(2C),131.8,131.4,130.1,129.6,129.5,129.4,128.5,128.3(2C) ,128.2,127.5,127.3,127.1,126.8,126.7,126.5,126.4,125.6,123.3(q,J C-F =273.3Hz),123.2(q,J C-F =272.8Hz),121.8(m),121.6(m),103.7,78.1,77.6,37.4,21.0,20.0. 19 F NMR (376MHz, CDCl3): δ-62.8,-62.9; HRMS (ESI-TOF) m / z Calcd.for C 116 H 73 F 24 O 10 NaI + [M+Na] + :2231.3757;Found:2231.3747.

[0082] Embodiment 6:

[0083]

[0084] The preparation method is the same as that of Example 1, light yellow solid, 398 mg, two-step total yield 40%; 1 H NMR(400MHz, CDCl3)δ7.96(s,2H),7.92(s,2H),7.90–7.76(m,4H),7.54–7 .36(m,6H),7.27(t,J=7.4Hz,3H),7.25–7.10(m,15H),7.10–7.00(m,8H),6 .93(s,2H),6.59(s,4H),5.98(s,1H),4.66(s,2H),4.21(d,J=9.2Hz,2H), 2.34(s,12H),2.16(s,12H),2.12(s,6H),2.10–1.63(m,4H),1.35(s,12H). 13C NMR (151MHz, CDCl3) δ167.3,156.9,145.8,144.6,139.8,138.0,137.9,13 7.6,135.3,133.2,132.6,132.2,132.0,131.1,130.7,129.7,129.4,129.3 ,128.8,128.4,128.1,127.9,127.7,127.6,127.3,127.0,126.8,126.6,1 26.2,125.3,104.0,77.6,37.2,21.6,21.2,21.1,19.3.HRMS(ESI-TOF)m / z Calcd.for C 116 H 97 INaO 10 + [M+Na] + :1799.6019;Found:1799.5984.

[0085] Embodiment 7:

[0086]

[0087] To a 25 mL Schlenk bottle, m-chloroperbenzoic acid (85%, 40.5 mg, 0.20 mmol), aryl iodide catalyst 1 (0.01 mmol), p-toluenesulfonic acid hydrate (38.0 mg, 0.20 mmol) and propiophenone (26.8 mg, 0.2 mmol) were added, and then 2 mL of ethyl acetate was added to dissolve, and then stirred at room temperature for 48 h. After the reaction was completed, the reaction was quenched with saturated sodium bicarbonate aqueous solution and extracted with ethyl acetate (3×15 mL). The combined organic phase was washed with saturated sodium chloride, dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether / ethyl acetate (5:1) as the eluent to obtain a white solid 4a (40.7 mg, yield 67%). 1 H NMR (400MHz, CDCl3) δ7.87(d,J=8.0Hz,2H),7.75(d,J=8.0Hz,2H),7.59(t,J=7.4Hz,1H),7.45(t ,J=7.6Hz,2H),7.27(d,J=8.0Hz,2H),5.79(q,J=6.8Hz,1H),2.40(s,3H),1.59(d,J=6.8Hz,3H). 13C NMR(101MHz, CDCl3)δ194.9,145.2,134.0,133.7,133.4,129.9,128.9,128.8,128.0,77.5,21.7,18.8.HRMS(EI-TOF)m / zCalcd.for C 16 H 16 O4S + [M] + :304.0769;Found:304.0767.

[0088] Table 1. Asymmetric sulfonyloxylation of α-position of propiophenone and its derivatives catalyzed by chiral aryl iodides

[0089]

[0090]

[0091] The above description is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by technicians in this technical field within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the rights.

Claims

1. An aryl iodide catalyst containing axial chirality and central chirality, characterized in that The chiral catalyst has a structure shown in general formula (I): In the general formula (I): The chirality marked with * is R configuration or S configuration, or racemic; R 1 Selected from C 1-6 Any of alkyl, cycloalkyl, aryl, heteroaryl, and arylmethyl; R 2 -R 7 are independently selected from hydrogen, halogen, C 1-6 Any of alkyl, cycloalkyl, aryl, heteroaryl, nitro, ester, cyano, and aldehyde groups; R 8 is hydrogen or aryl acyl.

2. The aryl iodide catalyst containing axial chirality and central chirality according to claim 1, characterized in that When the R 1 C 1-6 When 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 R is a cycloalkyl group, the cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group or a cyclooctyl group; 1 When R is aryl, the aryl is phenyl, methyl substituted phenyl, ethyl substituted phenyl, isopropyl substituted phenyl, tert-butyl substituted phenyl, neopentyl substituted phenyl, trifluoromethyl substituted phenyl, methoxy substituted phenyl, ethoxy substituted phenyl, tert-butyloxy substituted phenyl, fluorine substituted phenyl, chlorine substituted phenyl, bromine substituted phenyl; when R 1 When R is a heteroaryl group, the heteroaryl group is furyl, thienyl, indolyl, pyridyl or quinolyl; 1 When it is an arylmethyl group, the arylmethyl group is benzyl, methyl-substituted benzyl, ethyl-substituted benzyl, isopropyl-substituted benzyl, tert-butyl-substituted benzyl, neopentyl-substituted benzyl, trifluoromethyl-substituted benzyl, methoxy-substituted benzyl, ethoxy-substituted benzyl, tert-butyloxy-substituted benzyl, fluorine-substituted benzyl, chlorine-substituted benzyl, bromine-substituted benzyl or naphthylmethyl; When the R 2 -R 7 C 1-6 When 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 2 -R 7 When each of R is independently a cycloalkyl, the cycloalkyl is a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl group; when R 2 -R 7 When they are independently aryl, the aryl is phenyl, methyl substituted phenyl, ethyl substituted phenyl, isopropyl substituted phenyl, tert-butyl substituted phenyl, neopentyl substituted phenyl, trifluoromethyl substituted phenyl, methoxy substituted phenyl, ethoxy substituted phenyl, tert-butyloxy substituted phenyl, fluorine substituted phenyl, chlorine substituted phenyl, bromine substituted phenyl or naphthyl; when the R 2 -R 7 When they are independently heteroaryl, the heteroaryl is furyl, thienyl, indolyl or pyridyl; When the R 8 When it is an aryl acyl group, the aryl acyl group is phenyl acyl, methyl substituted phenyl acyl, ethyl substituted phenyl acyl, isopropyl substituted phenyl acyl, tert-butyl substituted phenyl acyl, neopentyl substituted phenyl acyl, trifluoromethyl substituted phenyl acyl, methoxy substituted phenyl acyl, ethoxy substituted phenyl acyl, tert-butyloxy substituted phenyl acyl, fluorine substituted phenyl acyl, chlorine substituted phenyl acyl, bromine substituted phenyl acyl or naphthyl acyl.

3. A method for preparing an aryl iodide catalyst containing axial chirality and central chirality as claimed in claim 1 or 2, wherein the preparation method is as follows: Preparation of an aryl iodine catalyst containing axial chirality and central chirality: an aryl iodine compound of structural formula a and a binaphthyl axial chiral compound of structural formula b are dissolved in an organic solvent, reacted at 0 to 150° C. for 1 to 60 hours under the action of a condensing agent to obtain an intermediate c, and the intermediate c reacts with a compound d under the action of a base to finally obtain a product 1; X in the compound a is selected from a hydroxyl group or an amine group; The chirality marked with * is R configuration or S configuration, or racemic.

4. The method for preparing an aryl iodide catalyst containing axial chirality and central chirality according to claim 3, characterized in that: The organic solvent is one or more of methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, chloroform, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane, ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide; The condensing agent is selected from one of dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI); In the preparation method of the aromatic iodide catalyst containing axial chirality and central chirality, the feeding ratio of compound a to compound b is a molar ratio of 1:6 to 6:1; In the method for preparing the aromatic iodine catalyst containing axial chirality and central chirality, the feeding ratio of compound c to compound d is a molar ratio of 1:10 to 10:

1.

5. A method for synthesizing α-sulfonyloxypropiophenone and its derivatives, characterized in that: The method for synthesizing α-sulfonyloxypropiophenone and its derivatives comprises the following steps: At the desired reaction temperature, using the aromatic iodine containing axial chirality and central chirality as claimed in claim 1 as a catalyst, under the action of m-chloroperbenzoic acid, compound 2 and compound 3 are reacted in an organic solvent as follows to obtain compound 4 after the desired reaction time; Among them, R 9 -R 13 R is independently -alkyl, aryl, heteroaryl, carboxyl, ester, aldehyde, acyl, amine, halogen or nitro; 14-15 is selected from alkyl, aryl, heteroaryl; The chirality marked with * is S configuration or R configuration or racemic.

6. The method for synthesizing α-sulfonyloxypropiophenone and its derivatives according to claim 5, characterized in that: When R 9 -R 13 When any of R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl or cyclohexyl; when the R 9 -R 13 When any of is an aryl group, the aryl group is phenyl, methyl substituted phenyl, ethyl substituted phenyl, isopropyl substituted phenyl, tert-butyl substituted phenyl, neopentyl substituted phenyl, trifluoromethyl substituted phenyl, methoxy substituted phenyl, ethoxy substituted phenyl, tert-butyloxy substituted phenyl, fluorine substituted phenyl, chlorine substituted phenyl, bromine substituted phenyl; when the R 9 -R 13 When any one of the heteroaryl groups is selected from , the heteroaryl group is furanyl, thienyl, indolyl or pyridyl; When the R 14-15 When selected from alkyl, the alkyl is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl or cyclohexyl; when the R 14-15 When selected from aryl, the aryl is phenyl, methyl substituted phenyl, ethyl substituted phenyl, isopropyl substituted phenyl, tert-butyl substituted phenyl, neopentyl substituted phenyl, trifluoromethyl substituted phenyl, methoxy substituted phenyl, ethoxy substituted phenyl, tert-butyloxy substituted phenyl, fluorine substituted phenyl, chlorine substituted phenyl, bromine substituted phenyl; when R 14-15 When selected from heteroaryl, the heteroaryl is furyl, thienyl, indolyl or pyridyl; The organic solvent is one or more of methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, chloroform, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane, ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide; The molar concentration of the compound 2 and the compound 3 in the organic solvent is 0.01 to 2.0 M; The molar ratio of the meta-chloroperbenzoic acid to the aryl iodide catalyst 1 containing axial chirality and central chirality is 10:1 to 30:1; The reaction temperature is -30 to 100°C; The reaction time is 1 to 96 hours.

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