A chiral aryl iodide catalyst using threonine as a chiral source, its synthesis method and application

Abstract

The present invention discloses a chiral aryl iodide catalyst using threonine as a chiral source, its synthesis method and application. The structural formula of the chiral aryl iodide catalyst is shown in Formula (12) or Formula (14), wherein R 1 is selected from a silyl protecting group, and R 2 is selected from methyl, trifluoromethyl, methyl ester or ethyl ester; R 3 is selected from acetyl, trifluoroacetyl, trichloroacetyl, tert-butylacetyl, benzoyl, substituted benzoyl, and the substituent on the substituted phenyl is mono-substituted or multi-substituted, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro; R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 each independently is selected from an alkane, a phenyl group or a substituted phenyl group, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro; The catalyst of the present invention has the advantages of high enantioselectivity, low price and low toxicity in asymmetric organic catalysis.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic compound synthesis, and particularly relates to a chiral aryl iodide catalyst using threonine as a chiral source, and a synthesis method and application thereof. Background Art

[0002] Hypervalent iodides have unique metallic properties. In organic synthesis, it is itself a versatile, low-toxic, easy-to-handle, stable and environmentally friendly oxidant. Thus, under the same conditions, and even in some cases more efficient than various transition metals, it realizes the "quasi-metallic" oxidative transformation of a large number of important skeletons. In this regard, the asymmetric reactions using these chiral organic iodides have become state-of-the-art technologies, with high applicability and versatility in modern organic synthesis. Because compared with metal catalysis and enzyme-catalyzed oxidation, it is difficult to achieve high stereoselectivity at the relevant transition states in such methods. The past decade has witnessed great progress in enantioselective hypervalent iodide catalysis in asymmetric organic catalyzed oxidation, which has proven to be a challenging field. Therefore, the development of efficient chiral organic iodide catalysts to achieve various asymmetric transformations and obtain enantiomeric structures is still highly desired.

[0003] Structurally, the chiral sources provided on the reported catalysts have only one chiral center, which may reduce the richness and tunability of the chiral environment of the catalyst, thereby inhibiting its synthetic diversity and reactivity. Therefore, it is of great significance to design and synthesize a new conformational flexible catalyst library with easy availability, high reactivity and recyclability. Summary of the Invention

[0004] The present invention overcomes many disadvantages of the traditional construction of chiral aryl iodide catalysts, and innovatively develops a chiral aryl iodide catalyst using threonine as a chiral source, and a synthesis method and application thereof.

[0005] A chiral aryl iodide catalyst using threonine as a chiral source, the structural formula of which is shown in formula (12) or formula (14),

[0006]

[0007] wherein R 1 is selected from silyl protecting groups, and the silyl protecting groups are trimethylsilyl, triethylsilyl, triethylpropylsilyl, diethylisopropylsilyl, dimethyltert-butylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl; R 2 is selected from methyl, trifluoromethyl, methyl ester or ethyl ester; R 3Selected from acetyl, trifluoroacetyl, trichloroacetyl, tert-butylacetyl, benzoyl or substituted benzoyl, the substituent on the substituted phenyl is mono-substituted or multi-substituted, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro; R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are each independently selected from alkane, phenyl or substituted phenyl, the substituent on the substituted phenyl is mono-substituted or multi-substituted, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro.

[0008] A method for synthesizing a chiral aryl iodide catalyst, comprising the following steps:

[0009] 1) The D-threonine shown in formula (1) is esterified and the amino group is protected to generate an intermediate shown in formula (2). The intermediate shown in formula (2) and a reducing agent are added to a solvent, and reacted to obtain an intermediate shown in formula (3);

[0010] 2) The intermediate shown in formula (3) reacts with a silyl protecting group in the presence of a base in a solvent to generate an intermediate shown in formula (4);

[0011] 3) The intermediate shown in formula (4) reacts with thionyl chloride in the presence of imidazole and triethylamine in a solvent to generate an intermediate shown in formula (5);

[0012] 4) The intermediate shown in formula (5) is oxidized in a solvent under the action of sodium periodate and ruthenium trichloride hydrate to generate an intermediate shown in formula (6);

[0013] 5) The intermediate shown in formula (6) and the 2-iodobenzenediol derivative shown in formula (7) react in a solvent under the action of sodium hydride to generate an intermediate shown in formula (8);

[0014] 6) The intermediate shown in formula (8) is deprotected by silyl in a solvent under the action of tetrabutylammonium fluoride to generate an intermediate shown in formula (9);

[0015] 7) The intermediate shown in formula (9) reacts with an acyl chloride in the presence of triethylamine in a solvent to generate an intermediate shown in formula (10);

[0016] 8) The intermediate shown in formula (8) or formula (10) is deprotected in a solvent under the action of trifluoroacetic acid to generate an intermediate shown in formula (11) or formula (13) respectively;

[0017] 9) The intermediate shown in formula (11) or formula (13) reacts with an acyl chloride, a sulfonamide, an isocyanate or an isothiocyanate under the action of triethylamine in a solvent to respectively generate the chiral aryl iodide catalyst shown in formula (12) or formula (14);

[0018] The reaction process is as follows:

[0019]

[0020]

[0021] Wherein R 1 is selected from silyl protecting groups, and the silyl protecting groups are trimethylsilyl, triethylsilyl, triethylpropylsilyl, diethylisopropylsilyl, dimethyltert-butylsilyl, tert-butyldimethylsilyl or tert-butyldiphenylsilyl; R 2 is selected from methyl, trifluoromethyl, methyl ester or ethyl ester; R 3 is selected from acetyl, trifluoroacetyl, trichloroacetyl, tert-butylacetyl, benzoyl or substituted benzoyl, and the substituents on the substituted phenyl are mono-substituted or multi-substituted, and the substituents are methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro; R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 each independently is selected from an alkane, a phenyl or a substituted phenyl, and the substituents on the substituted phenyl are mono-substituted or multi-substituted, and the substituents are methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro.

[0022] Furthermore, the reducing agent in step 1) is sodium borohydride, lithium aluminum hydride or diisobutylaluminum hydride, the solvent is methanol or ethanol, the dosage of the reducing agent is 1.0 - 10.0 equivalents of the intermediate shown in formula (2), the reaction temperature is -20 - 0 °C, and the reaction time is 2 - 7 h.

[0023] Furthermore, the hydroxy protecting group in step 2) is a silyl protecting group, wherein the source of the silyl protecting group is trimethylchlorosilane, triethylchlorosilane, triethylpropylchlorosilane, diethylisopropylchlorosilane, dimethyltert-butylchlorosilane, tert-butyldimethylchlorosilane and tert-butyldiphenylchlorosilane, the dosage of the silyl protecting group is 1.0 - 5.0 equivalents of the intermediate shown in formula (3); the dosage of the imidazole is 1.0 - 5.0 equivalents of the intermediate shown in formula (3); the solvent is dichloromethane, dichloroethane or chloroform, the reaction temperature is -20 - 0 °C, and the reaction time is 2 - 5 h.

[0024] Further, the dosage of thionyl chloride in step 3) is 1.0 - 5.0 equivalents of the intermediate shown in formula (4); the dosage of imidazole is 1.0 - 10.0 equivalents of the intermediate shown in formula (4); the dosage of triethylamine is 2.0 - 10.0 equivalents of the intermediate shown in formula (4); the solvent is dichloromethane, dichloroethane or chloroform, the reaction temperature is -70 - 0 °C, and the reaction time is 2 - 5 h.

[0025] Further, the dosage of sodium periodate in step 4) is 1.0 - 5.0 equivalents of the intermediate shown in formula (5); the dosage of ruthenium(III) chloride hydrate is 1 - 30 mol% of the intermediate shown in formula (5); the solvent is acetonitrile and water or dichloromethane and water, the dosage of the solvent is 5:6, the reaction temperature is 0 - 30 °C, and the reaction time is 2 - 6 h.

[0026] Further, the dosage of the intermediate shown in formula (6) in step 5) is 2.0 - 10.0 equivalents of the 2-iodocatechol derivative shown in formula (7); the dosage of sodium hydride is 2.0 - 10.0 equivalents of the 2-iodocatechol derivative shown in formula (7); the solvent is N,N-dimethylformamide, tetrahydrofuran or N,N-dimethylaniline, the reaction temperature is -20 - 0 °C, and the reaction time is 2 - 6 h.

[0027] Further, the dosage of tetrabutylammonium fluoride in step 6) is 2.0 - 10.0 equivalents of the intermediate shown in formula (8); the solvent is N,N-dimethylformamide, tetrahydrofuran or N,N-dimethylaniline, the reaction temperature is 0 - 30 °C, and the reaction time is 2 - 6 h; the dosage of the acyl chloride in step 7) is 2.0 - 10.0 equivalents of the intermediate shown in formula (9); the dosage of triethylamine is 2.0 - 10.0 equivalents of the intermediate shown in formula (9); the solvent is dichloromethane, dichloroethane or chloroform, the reaction temperature is -20 - 0 °C, and the reaction time is 1 - 4 h.

[0028] Further, the solvent in step 8) is dichloromethane, dichloroethane or chloroform, the dosage of trifluoroacetic acid and the solvent is 1:3 - 1:10, the reaction temperature is 0 - 30 °C, and the reaction time is 1 - 5 h. In step 9), the dosage of the acyl chloride, sulfonamide, isocyanate or isothiocyanate is 2.0 - 10.0 equivalents of the intermediate shown in formula (11) or formula (13); the dosage of triethylamine is 2.0 - 10.0 equivalents of the intermediate shown in formula (11) or formula (13); the solvent is dichloromethane, dichloroethane or chloroform, the reaction temperature is -20 - 0 °C, and the reaction time is 1 - 4 h.

[0029] Application of a chiral aryl iodide catalyst using threonine as a chiral source, specifically, the chiral aryl iodide catalyst enantioselectively synthesizes γ-butyrolactone, chroman ring, isochroman ring, oxazolidinone, piperidine, pyrrolidine, and aziridine through intramolecular oxidative lactonization, etherification, amidation, and arylation reactions.

[0030] Application of the present invention:

[0031] The catalyst disclosed in the present invention using D-threonine as a chiral source can be applied to catalyze 1-naphthol derivatives shown in formulas (15), (17), and (19) to correspondingly generate the products shown in formulas (16), (18), and (20) through a one-step reaction, or can also be applied to the malonamide derivative shown in formula (21) to generate the product shown in formula (22) through a one-step reaction.

[0032]

[0033] Advantages of the present invention:

[0034] 1) Using D-threonine as a chiral source, overcoming the drawback of only having one chiral center in the prior art, designing and synthesizing a hypervalent iodine catalyst with high catalytic activity;

[0035] 2) The preparation of the compounds of the present invention realizes a gram-scale reaction, has practicality, has a wide application prospect, and is suitable for industrial-scale production;

[0036] 3) The reaction of the present invention is efficient, has a high yield, is simple to prepare, stable, and has no pungent odor, and the reaction conditions are mild.

[0037] 4) The catalyst disclosed in the present invention has a good catalytic effect, has the advantages of high yield and high stereoselectivity, and provides an effective way for the synthesis of chiral heterocyclic compounds. Specific embodiments

[0038] The following further details the present invention in conjunction with the following specific embodiments. The protection scope of the present invention is not limited to the following embodiments. Without departing from the spirit and scope of the inventive concept, changes and advantages that those skilled in the art can think of are included in the present invention, and the appended claims are used as the protection scope. The processes, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the specifically mentioned content below, are all common knowledge and well-known common sense in the art, and the present invention has no special limiting content. The data given in the following embodiments include specific operations, reaction conditions, and products, and the product purity is identified by nuclear magnetic resonance.

[0039] A synthesis reaction of a chiral aryl iodide catalyst using D-threonine as a chiral source, and the reaction process is as follows:

[0040]

[0041]

[0042] Example 1

[0043] (4S,5R)-4-((tert-Butyldiphenylsilyloxy)methyl)-5-methyl-1,2,3-oxathiazolidine-3-carboxylic acid tert-butyl ester-2,2-dioxide synthesis:

[0044]

[0045] Sodium borohydride (11.4 g, 300 mmol, 3.0 equiv.) and methanol (100 mL) were added to a round-bottom flask. Then, (tert-Butoxycarbonyl)-D-threonine methyl ester (23.3 g, 100 mmol, 1.0 equiv.) dissolved in 200 mL of methanol was added dropwise at 0 °C. After reacting for 2 h, the methanol was evaporated under reduced pressure. The reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, and the solvent was removed under reduced pressure to obtain crude product 3 (12.3 g).

[0046] (2S,3S)-1,3-Dihydroxybutane-2-carbamic acid tert-butyl ester (3) (12.3 g, 60 mmol, 1.0 equiv.), imidazole (4.9 g, 72 mmol, 1.2 equiv.) and dichloromethane (200 mL) were added to a round-bottom flask. Then, tert-Butyldiphenylchlorosilane (18.2 g, 66 mmol, 1.1 equiv.) was added dropwise at 0 °C. After reacting for 2 h, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, and the solvent was removed under reduced pressure to obtain crude product 4a (25.3 g).

[0047] Under nitrogen protection, crude product tert-butyl ((2S,3S)-1-(tert-butyldiphenylsilyloxy)-3-hydroxybutane)-2-carbamic acid tert-butyl ester tert-butyl (4a) (25.3 g) obtained in step 2), imidazole (11.6 g, 171.0 mmol, 3.0 equiv.) and dichloromethane (200 mL) were added to a three-necked flask tube. Then, triethylamine (13.8 g, 136.8 mmol, 2.4 equiv) was added dropwise at -40 °C. After the addition was complete, thionyl chloride (8.1 g, 68.4 mmol, 1.2 equiv.) was added dropwise. After reacting for 4 h, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, and the solvent was removed under reduced pressure to obtain crude product 5a (25.1 g).

[0048] Under nitrogen protection, the crude product (4S,5R)-4-((tert-butyldiphenylsilyl)oxy)methyl)-5-methyl-1,2,3-oxathiazolidine-3-carboxylic acid tert-butyl ester-2-oxide (5a) (25.1 g) obtained in step 3) was dissolved in acetonitrile and water (5:6) (220 mL). Ruthenium(III) chloride trihydrate (106.4 mg, 1 mo1%) and sodium periodate (12.2 g, 56.4 mmol, 1.1 equiv.) were added successively, and the reaction was carried out for 4 h. The mixture was extracted with ethyl acetate, the organic phase was separated, and the solvent was removed under reduced pressure. After purification by column chromatography, 6a was obtained, with a total of 22.5 g (eluent polarity: PE:EA 10:1), and the four-step yield was 44.6%.

[0049] 1 H NMR(400MHz,CDCl3):δ7.60(t,J=1.2Hz,2H),7.57(q,J=1.1Hz,2H),7.40-7.34(m,4H),7.32-7.27(m,2H),5.42-5.37(m,1H),3.73-3.68(m,1H),3.65-3.63(m,1H),3.63-3.61(m,1H),1.43(d,J=6.9Hz,12H),1.05(s,9H). 13 CNMR(100MHz,CDCl3):δ153.1,133.4,132.2,129.5,128.7,81.6,78.9,69.4,57.7,28.3,26.8,18.3,16.5.HRMS(ESI-TOF)m / z:[M+H] + Calcd for C 25 H 35 NO6SSi505.1954;Found 505.1948;

[0050] Example 2

[0051] Synthesis of di-tert-butyl ((2S,2'S,3R,3'R)-(((2-iodo-1,3-phenylene)bis(oxy)bis(1-((tert-butyldiphenylsilyl)oxy)butane-3,2-diyl)) dicarbamate:

[0052]

[0053] Under a nitrogen atmosphere, 2-iodobenzene-1,3-diol (7a) (2.4 g, 10.0 mmol, 1.0 equiv.) and anhydrous DMF (50 mL) were added to a dry three-necked flask. Then, sodium hydride (552.0 mg, 23.0 mmol, 2.3 equiv.) was added at 0 °C. After stirring for 0.5 h, (4S,5R)-4-((tert-butyldiphenylsilyloxy)methyl)-5-methyl-1,2,3-oxathiazolane-3-carboxylic acid tert-butyl ester-2,2-dioxide (6a) (12.6 g, 25 mmol, 2.5 equiv.) dissolved in 80 mL of anhydrous DMF was added, and the reaction was carried out for 2 h. The reaction was quenched with dilute hydrochloric acid, extracted with ethyl acetate, and the organic phase was separated. After removing the solvent under reduced pressure, the product 8a (8.9 g, 82%) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0054] 1 1H NMR (400 MHz, CDCl3): δ 7.54 (d, J = 7.0 Hz, 4H), 7.45 (d, J = 7.0 Hz, 4H), 7.33–7.22 (m, 8H), 7.19–7.13 (m, 5H), 7.06 (t, J = 8.2 Hz, 1H), 6.32 (d, J = 8.2 Hz, 2H), 4.82 (d, J = 9.3 Hz, 2H), 4.59–4.44 (m, 2H), 4.02 (dd, J = 10.9, 3.9 Hz, 2H), 3.88 (m, 2H), 3.80 (m, 2H), 1.35 (s, 18H), 1.26 (d, J = 5.9 Hz, 6H), 0.92 (s, 18H). 13 13C NMR (100 MHz, CDCl3): δ 157.9, 155.8, 135.7, 133.4, 133.0, 129.9, 129.8, 129.7, 127.9, 127.8, 105.7, 81.3, 79.5, 77.4, 74.8, 62.8, 56.3, 28.5, 27.0, 19.3, 16.6. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 56 H 75 IN2O8Si2 1086.4107; Found 1086.4123;

[0055] Example 3

[0056] (2S,2'S,3R,3'R)-((2-Iodo-1,3-phenylene)bis(oxy)bis(2-(tert-butoxycarbonyl)amino)butane-3,1-diyl)bis(2,4,6-trimethylbenzoate) synthesis:

[0057]

[0058] Under a nitrogen atmosphere, di-tert-butyl ((2S,2'S,3R,3'R)-(((2-iodo-1,3-phenylene)bis(oxy)bis(1-((tert-butyldiphenylsilyl)oxy)butane-3,2-diyl)) dicarbamate (8a) (5.4 g, 5.0 mmol, 1.0 equiv.) and anhydrous THF (50 mL) were added to a dry round-bottom flask. Then, tetrabutylammonium fluoride (3.9 g, 15.0 mmol, 3.0 equiv.) was added at 20 °C. After reacting for 3 h, the reaction was quenched with water, extracted with ethyl acetate, the organic phase was separated, and the solvent was removed under reduced pressure to obtain the crude product 9a (2.9 g).

[0059] Under a nitrogen atmosphere, di-tert-butyl (2S,2'S,3R,3'R)-(((2-iodo-1,3-phenylene)bis(oxy))bis(1-hydroxybutane-3,2-diyl)) dicarbamate (9a) (2.9 g, 4.75 mmol, 1.0 equiv.), triethylamine (1.2 g, 11.9 mmol, 2.5 equiv.) and anhydrous DCM (50 mL) were added to a dry three-necked flask. Then, 2,4,6-trimethylbenzoyl chloride (1.9 g, 10.5 mmol, 2.2 equiv.) was added at 0 °C. After reacting for 2 h, the reaction was quenched with water, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. After purification by column chromatography, the product 10a (3.0 g) was obtained (eluent polarity: PE:EA 6:1), and the two-step yield was 66.5%.

[0060] 1 H NMR (400 MHz, CDCl3): δ 7.29 (t, J = 7.7 Hz, 1H), 6.84 (s, 4H), 6.43 (d, J = 7.7 Hz, 2H), 5.27 (d, J = 8.4 Hz, 2H), 4.69 - 4.58 (m, 2H), 4.50 (dd, J = 10.8, 4.2 Hz, 2H), 4.38 - 4.26 (m, 4H), 2.30 (d, J = 0.6 Hz, 6H), 2.27 (s, 12H), 1.48 (s, 18H), 1.38 (d, J = 2.1 Hz, 3H), 1.36 (d, J = 1.7 Hz, 3H). 1313C NMR (100 MHz, CDCl3): δ 166.6, 156.6, 156.3, 139.9, 135.3, 132.6, 129.8, 129.4, 129.1, 128.2, 128.0, 109.3, 78.7, 73.6, 73.3, 62.6, 54.8, 28.3, 21.2, 19.1, 16.9. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 44 H 59 IN2O 10 902.3214; Found 902.3205;

[0061] Example 4

[0062] Synthesis of bis(2,4,6-trimethylbenzoate) of (2-iodo-1,3-phenylene)dioxy:

[0063]

[0064] Under a nitrogen atmosphere, (2S,2'S,3R,3'R)-((2-iodo-1,3-phenylene)bis(oxy)bis(2-(tert-butoxycarbonyl)amino)butane-3,1-diyl)bis(2,4,6-trimethylbenzoate) (10a) (2.7 g, 3.0 mmol, 1.0 equiv.) and anhydrous DCM (10 mL) were added to a dry round-bottom flask. Then, trifluoroacetic acid (3.4 g, 30.0 mmol, 10.0 equiv.) was added at room temperature. After reacting for 2 h, the reaction was quenched with an aqueous sodium bicarbonate solution, extracted with dichloromethane, and the organic phase was separated. After removing the solvent under reduced pressure, the product 13a (2.0 g, 95%) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0065] 1 1H NMR (400 MHz, CDCl3): δ 7.24 (t, J = 8.0 Hz, 1H), 6.86 (s, 4H), 6.43 (d, J = 7.7 Hz, 2H), 4.56 (dd, J = 12.3, 4.7 Hz, 2H), 4.29 (dd, J = 12.4, 4.6 Hz, 2H), 3.67 - 3.59 (m, 4H), 3.44 (t, J = 7.2 Hz, 2H), 2.87 (t, J = 7.1 Hz, 2H), 2.28 (d, J = 12.1 Hz, 18H), 1.36 (dd, J = 4.9, 1.8 Hz, 6H). 1313C NMR (100 MHz, CDCl3): δ 166.6, 156.7, 140.5, 135.3, 131.9, 129.3, 129.1, 129.0, 128.6, 128.4, 110.5, 76.6, 74.3, 63.7, 55.1, 21.3, 19.1, 16.1. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 34 H 43 IN2O6 702.2166; Found 702.2163;

[0066] Example 5

[0067] (2S,2'S,3R,3'R)-3,3'-(2-Iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyloxy)butan-2-amine) Synthesis:

[0068]

[0069] Under a nitrogen atmosphere, di-tert-butyl ((2S,2'S,3R,3'R)-(((2-iodo-1,3-phenylene)bis(oxy)bis(1-((tert-butyldiphenylsilyloxy)butane-3,2-diyl)) dicarbamate (8a) (5.4 g, 5.0 mmol, 1.0 equiv.) and anhydrous DCM (15 mL) were added to a dry round-bottom flask. Then, trifluoroacetic acid (5.7 g, 50.0 mmol, 10.0 equiv.) was added at room temperature. After reacting for 2 h, the reaction was quenched with an aqueous sodium bicarbonate solution, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 11a (4.2 g, 94%) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0070] 1 1H NMR (400 MHz, CDCl3): δ 7.69 - 7.65 (m, 4H), 7.64 - 7.61 (m, 4H), 7.39 (d, J = 7.3 Hz, 5H), 7.33 (dd, J = 7.8, 6.4 Hz, 5H), 7.15 (t, J = 8.2 Hz, 1H), 6.44 (d, J = 8.3 Hz, 2H), 4.66 - 4.41 (m, 2H), 3.83 (m, 4H), 3.25 - 3.11 (m, 2H), 1.72 (s, 6H), 1.31 (d, J = 6.2 Hz, 6H), 1.06 (s, 18H). 1313C NMR (100 MHz, CDCl3) δ 157.7, 135.6, 135.5, 133.3, 133.2, 129.7, 129.7, 129.5, 127.7, 127.7, 106.0 81.6, 76.0, 65.3, 56.5, 26.9, 19.2, 15.0. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 46 H 59 IN2O4Si2886.3058; Found 886.3063;

[0071] Example 6

[0072] Synthesis of N,N'-(2S,2'S,3R,3'R)-((2-Iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyloxy)butane-3,2-diyl))bis(2,2-dimethylpropanamide):

[0073]

[0074] Under a nitrogen atmosphere, (2S,2'S,3R,3'R)-3,3'-(2-Iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyloxy)butan-2-amine) (11a) (886.3 mg, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (2.0 mL) were added to a dry schlenk tube, and then t BuCOCl (265.3 mg, 2.2 mmol, 2.2 equiv.) was added dropwise at 0 °C. After reacting for 2 h, the reaction was quenched with water, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 12a (980.6 mg, 93%) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0075] 11H NMR (400 MHz, CDCl3): δ 7.68–7.58 (m, 4H), 7.54–7.48 (m, 4H), 7.41 (d, J = 7.2 Hz, 2H), 7.39–7.30 (m, 6H), 7.24 (t, J = 7.5 Hz, 4H), 7.15 (t, J = 8.2 Hz, 1H), 6.43 (d, J = 8.3 Hz, 2H), 6.18 (d, J = 8.6 Hz, 2H), 4.64 (t, J = 6.4 Hz, 2H), 4.35–4.18 (m, 4H), 3.84 (dd, J = 10.3, 3.3 Hz, 2H), 1.36 (d, J = 6.3 Hz, 6H), 1.15 (s, 18H), 1.02 (s, 18H). 13 13C NMR (100 MHz, CDCl3) 178.2, 158.3, 135.7, 135.6, 133.06, 132.7, 130.0, 129.9, 128.0, 127.9, 106.0, 81.1, 74.8, 62.3, 54.6, 38.9, 27.6, 26.9, 19.3, 16.8. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 56 H 75 IN2O6Si2 1055.4287; Found 1055.4289;

[0076] Example 7

[0077] Synthesis of N,N'-(2S,2'S,3R,3'R)-((2-Iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyl)oxy)butane-3,2-diyl))bis(2,4,6-trimethylbenzamide):

[0078]

[0079] Under a nitrogen atmosphere, (2S,2'S,3R,3'R)-3,3'-(2-iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyloxy)butan-2-amine) (11a) (886.3 mg, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (2.0 mL) were added to a dry Schlenk tube. Then, MesCOCl (401.8 mg, 2.2 mmol, 2.2 equiv.) was added dropwise at 0 °C. After reacting for 2 h, the reaction was quenched with water, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 12b (1205.3 mg, 87%) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0080] 1 H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 7.1 Hz, 4H), 7.46 (d, J = 7.1 Hz, 4H), 7.32 (t, J = 7.3 Hz, 2H), 7.25 (q, J = 7.3 Hz, 6H), 7.15 (dd, J = 13.6, 6.2 Hz, 4H), 7.09 (t, J = 8.2 Hz, 1H), 6.74 (s, 4H), 6.35 (d, J = 8.3 Hz, 2H), 5.93 (d, J = 8.6 Hz, 2H), 4.79–4.67 (m, 2H), 4.51–4.36 (m, 2H), 4.20 (dd, J = 10.7, 5.5 Hz, 2H), 3.95 (dd, J = 10.7, 3.1 Hz, 2H), 2.19 (s, 6H), 2.08 (s, 12H), 1.35 (d, J = 6.2 Hz, 6H), 0.94 (s, 18H). 13 C NMR (100 MHz, CDCl3) δ 170.6, 157.8, 138.6, 135.7, 135.7, 134.8, 134.3, 133.1, 132.8, 130.0, 129.9, 128.4, 128.0, 128.0, 105.8, 81.4, 77.5, 74.4, 62.5, 55.6, 27.0, 21.3, 19.3, 19.3, 16.7. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 66 H 79 IN2O6Si2 1179.4600; Found 1179.4610.

[0081] Example 8

[0082] Synthesis of N,N'-(2S,2'S,3R,3'R)-((2-Iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyloxy)butane-3,2-diyl))bis(4-nitrobenzamide):

[0083]

[0084] Under a nitrogen atmosphere, (2S,2'S,3R,3'R)-3,3'-(2-Iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyloxy)butan-2-amine) (11a) (886.3 mg, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (2.0 mL) were added to a dry Schlenk tube. Then, 4-nitrobenzoyl chloride (408.2 mg, 2.2 mmol, 2.2 equiv.) was added dropwise at 0 °C. After reacting for 2 h, the reaction was quenched with water, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 12c (1065.9 mg, 90%) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0085] 1 H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.7 Hz, 4H), 7.77 (d, J = 8.6 Hz, 4H), 7.62 (d, J = 7.6 Hz, 4H), 7.55 (d, J = 7.5 Hz, 4H), 7.42 (dd, J = 14.2, 6.9 Hz, 2H), 7.39–7.30 (m, 6H), 7.26 (dd, J = 8.6, 6.2 Hz, 4H), 7.17 (t, J = 8.2 Hz, 1H), 6.55 (t, J = 10.0 Hz, 2H), 6.45 (d, J = 8.3 Hz, 2H), 4.82–4.62 (m, 2H), 4.54 (m, 2H), 4.32 (dd, J = 10.6, 5.8 Hz, 2H), 4.08 (dd, J = 10.6, 3.6 Hz, 2H), 1.44 (d, J = 6.3 Hz, 6H), 1.02 (s, 18H). 13 C NMR (100 MHz, CDCl3) δ 165.2, 158.1, 149.7, 140.0, 135.8, 135.7, 133.2, 132.8, 130.2, 130.1, 128.3, 128.1, 128.0, 123.9, 106.3, 81.2, 75.4, 62.2, 55.7, 27.0, 19.4, 17.0. HRMS (ESI-TOF) m / z: [M+H] +Calcd for C 60 H 65 IN4O 10 Si2 1185.3362; Found 1185.3370.

[0086] Example 9

[0087] Synthesis of N,N'-(2S,2'S,3R,3'R)-((2-iodo-1,3-phenylene)bis(oxy)bis((2,4,6-trimethylbenzamido)butane-3,2-diyl))bis(2,4,6-trimethylbenzoate):

[0088]

[0089] Under a nitrogen atmosphere, (2S,2'S,3R,3'R)-3,3'-(2-iodo-1,3-phenylenebisoxy)bis(2,4,6-trimethylbenzoate) (13a) (702.2 mg, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (2.0 mL) were added to a dry Schlenk tube. Then, 2,4,6-trimethylbenzoyl chloride (408.2 mg, 2.2 mmol, 2.2 equiv.) was added dropwise at 0 °C. After reacting for 2 h, the reaction was quenched with water, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 14a (825.4 mg, 83%) was obtained by column chromatography purification (eluent polarity: PE:EA = 6:1).

[0090] 1 H NMR (400 MHz, CDCl3) δ 7.20 (t, J = 8.2 Hz, 1H), 6.81 (s, 4H), 6.77 (s, 4H), 6.45 (d, J = 8.3 Hz, 2H), 6.13 (d, J = 6.7 Hz, 2H), 4.86 (m, 2H), 4.72 (m, 6H), 2.26 (s, 6H), 2.24 (s, 18H), 2.11 (s, 12H), 1.52 (d, J = 5.9 Hz, 6H). 13 C NMR (100 MHz, CDCl3) δ 170.5, 170.0, 157.7, 139.7, 138.8, 135.5, 134.4, 134.2, 130.5, 130.1, 128.6, 128.4, 106.5, 81.7, 77.4, 75.8, 63.3, 52.8, 21.3, 21.2, 20.1, 19.1, 16.9. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C54 H 63 IN2O8995.3707; Found 995.3701.

[0091] Example 10

[0092] (2S,2'S,3R,3'R)-(2-Iodo-1,3-phenylene)bis(oxy)bis(2-(m-tolyl)ureidobutane-3,1-diyl)bis(2,4,6-trimethylbenzoate) Synthesis:

[0093]

[0094] Under a nitrogen atmosphere, (2S,2'S,3R,3'R)-3,3'-(2-Iodo-1,3-phenylene bis(oxy))bis(2,4,6-trimethylbenzoate) (13a) (702.2 mg, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (2.0 mL) were added to a dry schlenk tube. Then, m-tolyl isocyanate (292.9 mg, 2.2 mmol, 2.2 equiv.) was added dropwise at 0 °C. After reacting for 2 h, the reaction was quenched with water, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 14b (813.4 mg, 84%) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0095] 1 H NMR (400 MHz, CDCl3) δ 7.13 (t, J = 8.3 Hz, 1H), 7.07 (t, J = 7.8 Hz, 2H), 6.94 (d, J = 13.1 Hz, 2H), 6.90 (d, J = 8.1 Hz, 2H), 6.86–6.81 (m, 2H), 6.80 (s, 4H), 6.68 (s, 2H), 6.41 (d, J = 8.4 Hz, 2H), 5.54 (d, J = 8.2 Hz, 2H), 4.88 (dd, J = 11.6, 8.0 Hz, 2H), 4.62 (dd, J = 11.2, 3.4 Hz, 4H), 4.43 (m, 2H), 2.25 (s, 6H), 2.21 (d, J = 2.9 Hz, 18H), 1.42 (d, J = 6.3 Hz, 6H). 1313C NMR (100 MHz, CDCl3) δ 170.5, 157.8, 155.3, 139.7, 139.3, 138.1, 135.4, 130.6, 130.0, 129.2, 128.6, 124.9, 121.8, 118.1, 106.8, 81.6, 76.5, 63.6, 54.0, 21.5, 21.3, 19.9, 16.8. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 50 H 57 IN4O8 969.3299; Found 969.3304.

[0096] Example 11

[0097] Synthesis of N,N'-((2S,2'S,3R,3'R)-((2-Iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyloxy)butane-3,2-diyl))bis(4-methylbenzenesulfonamide):

[0098]

[0099] Under a nitrogen atmosphere, (2S,2'S,3R,3'R)-3,3'-(2-Iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyloxy)butan-2-amine) (11a) (886.3 mg, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (2.0 mL) were added to a dry Schlenk tube. Then, p-toluenesulfonyl chloride (419.4 mg, 2.2 mmol, 2.2 equiv.) was added dropwise at 0 °C. After reacting for 2 h, the reaction was quenched with water, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 12d (931.6 mg, 78%) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0100] 11H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.3 Hz, 4H), 7.46–7.39 (m, 6H), 7.36–7.27 (m, 10H), 7.15 (dd, J = 11.9, 7.7 Hz, 8H), 7.11 (s, 1H), 6.37 (d, J = 8.3 Hz, 2H), 5.10 (d, J = 8.5 Hz, 2H), 4.62 (t, J = 6.7 Hz, 2H), 4.04 (dd, J = 10.5, 2.9 Hz, 2H), 3.48 (t, J = 4.0 Hz, 2H), 3.29 (dd, J = 10.5, 3.9 Hz, 2H), 2.38 (s, 6H), 1.48 (d, J = 6.1 Hz, 6H), 0.95 (s, 18H). 13 13C NMR (100 MHz, CDCl3) δ 157.3, 143.5, 137.6, 135.6, 135.5, 132.7, 132.2, 123.0, 129.9, 129.8, 127.9, 127.1, 127.0, 105.5, 80.9, 77.4, 73.1, 61.5, 58.9, 26.9, 21.7, 19.3, 16.6. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 60 H 71 IN2O8S2Si2 1195.3313; Found 1195.3319.

[0101] Example 12

[0102] Synthesis of N,N'-((2S,2'S,3R,3'R)-((2-Iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyl)oxy)butane-3,2-diyl))bis(4-methylbenzenesulfonamide):

[0103]

[0104] Under a nitrogen atmosphere, (2S,2'S,3R,3'R)-3,3'-(2-iodo-1,3-phenylene)bis(oxy)bis(1-(tert-butyldiphenylsilyloxy)butan-2-amine) (11a) (886.3 mg, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (2.0 mL) were added to a dry Schlenk tube. Then phenyl isothiocyanate (297.4 mg, 2.2 mmol, 2.2 equiv.) was added dropwise at 0 °C. After reacting for 2 h, the reaction was quenched with water, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 12e (884.1 mg, 73%) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0105] 1 H NMR (400 MHz, CDCl3) δ 8.13–7.93 (m, 2H), 7.54–7.46 (m, 4H), 7.43–7.36 (m, 6H), 7.35–7.28 (m, 10H), 7.18 (t, J = 7.5 Hz, 4H), 7.14 (d, J = 8.3 Hz, 1H), 7.07 (d, J = 7.7 Hz, 4H), 6.53 (d, J = 8.7 Hz, 2H), 6.42 (d, J = 8.4 Hz, 2H), 4.97 (s, 2H), 4.80 (t, J = 6.2 Hz, 2H), 4.15 (dd, J = 10.6, 5.2 Hz, 2H), 3.91 (dd, J = 10.6, 3.8 Hz, 2H), 1.48 (d, J = 6.3 Hz, 6H), 0.88 (s, 18H). 13 C NMR (101 MHz, CDCl3) δ 180.5, 157.8, 135.6, 135.6, 132.8, 132.5, 130.5, 129.9, 129.9, 129.8, 127.9, 127.9, 127.6, 125.3, 105.5, 77.4, 74.3, 61.8, 60.7, 26.8, 19.2, 16.8. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 60 H 69 IN4O4S2Si2 1157.3422; Found 1157.3423.

[0106] Example 13

[0107] (S)-4'-ethyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione synthesis:

[0108]

[0109] Under a nitrogen atmosphere, 3-(4-ethyl-1-hydroxynaphthalen-2-yl)propanoic acid (15) (48.2 mg, 0.2 mmol, 1.0 equiv.), catalyst 12b (35.4 mg, 0.03 mmol, 15 mol%), m-chloroperbenzoic acid (52.0 mg, 0.3 mmol, 1.5 equiv.) and anhydrous DCM (10.0 mL) were added to a dry Schlenk tube. Then, anhydrous ethanol (46.1 mg, 1.0 mmol, 5.0 equiv.) was added dropwise at -20 °C. After reacting for 24 h, the reaction was quenched with sodium bicarbonate solution and sodium thiosulfate solution, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 16 (34.9 mg, 72%, -94% ee) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0110] 1 H NMR (400 MHz, CDCl3) δ 8.02 (dd, J = 7.7, 1.5 Hz, 1H), 7.66 (td, J = 7.7, 1.5 Hz, 1H), 7.45 (d, J = 7.9 Hz, 1H), 7.40 (td, J = 7.5, 1.1 Hz, 1H), 5.98 (d, J = 1.5 Hz, 1H), 2.86 (m, 1H), 2.62–2.55 (m, 2H), 2.54 (m, 1H), 2.39 (m, 1H), 2.16 (m, 1H), 1.23 (t, J = 7.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 197.0, 176.7, 138.3, 137.5, 135.6, 128.6, 128.1, 127.6, 127.2, 124.4, 83.9, 31.6, 26.9, 25.1, 12.4. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 15 H 14 O3 243.1021; Found 243.1017.

[0111] Optical Rotation: [α] 25 D -161.3 (c = 1.0, CHCl3).

[0112] Example 14

[0113] (S)-4'-Benzyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-dione synthesis:

[0114]

[0115] Under a nitrogen atmosphere, 3-(4-benzyl-1-hydroxynaphthalen-2-yl)propanoic acid (17) (61.2 mg, 0.2 mmol, 1.0 equiv.), catalyst 12b (35.4 mg, 0.03 mmol, 15 mol%), m-chloroperoxybenzoic acid (52.0 mg, 0.3 mmol, 1.5 equiv.) and anhydrous DCM (10.0 mL) were added to a dry Schlenk tube. Then, anhydrous ethanol (46.1 mg, 1.0 mmol, 5.0 equiv.) was added dropwise at -20 °C. After reacting for 24 h, the reaction was quenched with sodium bicarbonate solution and sodium thiosulfate solution, extracted with dichloromethane, and the organic phase was separated. After removing the solvent under reduced pressure, the product 18 (51.1 mg, 84%, -96% ee) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0116] 1 H NMR (400 MHz, CDCl3) δ 8.04 (dd, J = 7.7, 1.5 Hz, 1H), 7.59 (td, J = 7.7, 1.5 Hz, 1H), 7.45–7.35 (m, 2H), 7.36–7.29 (m, 2H), 7.30–7.21 (m, 3H), 5.90 (d, J = 1.4 Hz, 1H), 3.89 (s, 2H), 2.87 (m, 1H), 2.56 (m, 1H), 2.44 (m, 1H), 2.17 (m, 1H). 13 C NMR (100 MHz, CDCl3) δ 196.7, 176.6, 137.5, 137.2, 135.9, 135.6, 130.9, 128.9, 128.9, 128.8, 128.1, 127.7, 126.9, 125.2, 83.8, 38.8, 31.6, 26.8. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 20 H 16 O3 305.1178; Found 305.1176.

[0117] Optical Rotation: [α] 25 D -102.5 (c = 1.0, CHCl3).

[0118] Example 15

[0119] (S)-1-Methyl-1'H-spiro[indoline-3,2'-naphthalene]-1',2-dione synthesis:

[0120]

[0121] Under a nitrogen atmosphere, 1-hydroxy-N-methyl-N-phenyl-2-naphthamide (19) (55.4 mg, 0.2 mmol, 1.0 equiv.), catalyst 10c (35.3 mg, 0.03 mmol, 15 mol%), m-chloroperoxybenzoic acid (45.1 mg, 0.26 mmol, 1.3 equiv.), water (36 mg, 2.0 mmol, 10.0 equiv.) and nitromethane (3.0 mL) were added to a dry Schlenk tube. Then, trifluoroethanol (1000.4 mg, 10.0 mmol, 50.0 equiv.) was added dropwise at -10 °C. After reacting for 72 h, the reaction was quenched with sodium bicarbonate solution and sodium thiosulfate solution, extracted with dichloromethane, and the organic phase was separated. After removing the solvent under reduced pressure, the product 20 (31.4 mg, 57%, 91% ee) was obtained by column chromatography purification (eluent polarity: PE:EA 2:1).

[0122] 1 H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.7 Hz, 1H), 7.68 - 7.61 (m, 1H), 7.44 - 7.30 (m, 3H), 7.03 - 6.88 (m, 4H), 6.03 (d, J = 9.6 Hz, 1H), 3.29 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 194.1, 172.8, 144.9, 138.3, 135.4, 129.4, 129.3, 128.7, 128.7, 128.4, 128.1, 127.8, 123.5, 123.1, 109.0, 64.5, 27.0. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 18 H 13 N2O2 276.1025; Found 276.1020.

[0123] Optical Rotation: [α] 25 D -4.2 (c = 1, CHCl3).

[0124] Example 16

[0125] (S)-1,1'-Dimethyl-3,3'-spirobi[indoline]-2,2'-dione synthesis:

[0126]

[0127] Under a nitrogen atmosphere, N,N'-dimethyl-N,N'-diphenylpropanediamide (21) (56.4 mg, 0.2 mmol, 1.0 equiv.), catalyst 12a (31.6 mg, 0.03 mmol, 15 mol%), m-chloroperbenzoic acid (90.1 mg, 0.52 mmol, 2.6 equiv.), water (10.8 mg, 0.6 mmol, 3.0 equiv.) and nitromethane (3.0 mL) were added to a dry Schlenk tube. Then, trifluoroacetic acid (68.4 mg, 0.6 mmol, 3.0 equiv.) was added dropwise at -10 °C. After reacting for 72 h, the reaction was quenched with sodium bicarbonate solution and sodium thiosulfate solution, extracted with dichloromethane, the organic phase was separated, and the solvent was removed under reduced pressure. The product 22 (37.8 mg, 68%, 89% ee) was obtained by column chromatography purification (eluent polarity: PE:EA 6:1).

[0128] 1 H NMR (400 MHz, CDCl3) δ 7.38 (t, J = 7.6 Hz, 2H), 7.04 (t, J = 7.6 Hz, 2H), 6.96 (d, J = 7.8 Hz, 2H), 6.88 (d, J = 7.4 Hz, 2H), 3.30 (s, 6H); 13 C NMR (100 MHz, CDCl3) δ 172.2, 145.4, 129.6, 127.9, 123.9, 123.3, 108.8, 62.3, 27.0. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 17 H 14 N2O2 279.1134; Found 279.1130.

[0129] Optical Rotation: [α] 25 D -71 (c = 0.5, CHCl3).

Claims

1. A chiral aryl iodide catalyst using threonine as a chiral source, characterized in that Its structural formula is shown in Formula (12). wherein the substituent R 1 is tert-butyldiphenylsilyl, R 2 is H, R 4 is tert-butyl, mesityl or 4-nitrophenyl.

2. A method for synthesizing the chiral aryl iodide catalyst according to claim 1, characterized in that, It includes the following steps: 1) The D-threonine shown in Formula (1) is esterified and the amino group is protected to generate an intermediate shown in Formula (2). The intermediate shown in Formula (2) and a reducing agent are added to a solvent, and reacted to obtain an intermediate shown in Formula (3). 2) The intermediate shown in Formula (3) reacts with a silyl protecting group in the presence of a base in a solvent to generate an intermediate shown in Formula (4). 3) The intermediate shown in Formula (4) reacts with thionyl chloride in the presence of imidazole and triethylamine in a solvent to generate an intermediate shown in Formula (5). 4) The intermediate shown in Formula (5) is oxidized in a solvent under the action of sodium periodate and ruthenium(III) chloride hydrate to generate an intermediate shown in Formula (6). 5) The intermediate shown in Formula (6) and the 2-iodobenzenediol derivative shown in Formula (7) react in the presence of sodium hydride in a solvent to generate an intermediate shown in Formula (8). 6) The intermediate shown in Formula (8) removes the protecting group in a solvent under the action of trifluoroacetic acid to generate Formula (11) respectively. 7) The intermediate shown in Formula (11) reacts with an acyl chloride, a sulfonamide, an isocyanate or an isothiocyanate in the presence of triethylamine in a solvent to generate a chiral aryl iodide catalyst shown in Formula (12) respectively. The reaction process is as follows: Among them, the substituent R 1 is tert-butyldiphenylsilyl, R 2 is H, R 4 is tert-butyl, mesityl or 4-nitrophenyl.

3. The synthesis method according to claim 2, characterized in that, In Step 1), the reducing agent is sodium borohydride, lithium aluminum hydride or diisobutylaluminum hydride, the solvent is methanol or ethanol, the dosage of the reducing agent is 1.0 - 10.0 equivalents of the intermediate shown in Formula (2), the reaction temperature is -20 - 0 °C, and the reaction time is 2 - 7 h.

4. The synthesis method according to claim 2, characterized in that, In Step 2), the dosage of the silyl protecting group is 1.0 - 5.0 equivalents of the intermediate shown in Formula (3); the solvent is dichloromethane, dichloroethane or chloroform, the reaction temperature is -20 - 0 °C, and the reaction time is 2 - 5 h.

5. The synthesis method according to claim 2, characterized in that, In Step 3), the dosage of thionyl chloride is 1.0 - 5.0 equivalents of the intermediate shown in Formula (4); the dosage of imidazole is 1.0 - 10.0 equivalents of the intermediate shown in Formula (4); the dosage of triethylamine is 2.0 - 10.0 equivalents of the intermediate shown in Formula (4); the solvent is dichloromethane, dichloroethane or chloroform, the reaction temperature is -70 - 0 °C, and the reaction time is 2 - 5 h.

6. The synthesis method according to claim 2, characterized in that, In Step 4), the dosage of sodium periodate is 1.0 - 5.0 equivalents of the intermediate shown in Formula (5); the dosage of ruthenium(III) chloride hydrate is 1 - 30 mol% of the intermediate shown in Formula (5); the solvent is acetonitrile and water or dichloromethane and water, the dosage of the solvent is 5:6, the reaction temperature is 0 - 30 °C, and the reaction time is 2 - 6 h.

7. The synthesis method according to claim 2, wherein, In Step 5), the dosage of the intermediate shown in Formula (6) is 2.0 - 10.0 equivalents of the 2-iodobenzenediol derivative shown in Formula (7); the dosage of sodium hydride is 2.0 - 10.0 equivalents of the 2-iodobenzenediol derivative shown in Formula (7); the solvent is N,N-dimethylformamide, tetrahydrofuran or N,N-dimethylaniline, the reaction temperature is -20 - 0 °C, and the reaction time is 2 - 6 h.

8. The synthesis method according to claim 2, characterized in that, The solvent described in step 6) is dichloromethane, dichloroethane or chloroform. The dosage ratio of trifluoroacetic acid to the solvent is 1:3 - 1:

10. The reaction temperature is 0 - 30 °C and the reaction time is 1 - 5 h. The dosage of the acyl chloride, sulfonamide, isocyanate or isothiocyanate described in step 7) is 2.0 - 10.0 equivalents of the intermediate shown in formula (11); the dosage of triethylamine is 2.0 - 10.0 equivalents of the intermediate shown in formula (11); the solvent is dichloromethane, dichloroethane or chloroform, the reaction temperature is -20 - 0 °C, and the reaction time is 1 - 4 h.

9. Use of a chiral aryl iodide catalyst with threonine as a chiral source as described in claim 1, characterized in that, Specifically, the chiral aryl iodide catalyst enantioselectively synthesizes γ-butyrolactone through intramolecular oxidative lactonization.

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