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

Abstract

The present invention discloses a flexible chiral aryl iodide catalyst using chloramphenicol as a chiral source, a synthesis method and an application thereof, wherein the structural formula thereof is shown in formula (10), wherein R 1 is selected from hydroxy protecting groups including trimethylsilyl, triethylsilyl, triethylpropylsilyl, diethylisopropylsilyl, dimethyl-tert-butylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, acetyl, trifluoroacetyl, trichloroacetyl, tert-butylacetyl, benzoyl or substituted phenyl, wherein the substituents on the substituted phenyl are monosubstituted or polysubstituted; the substituent R 2 Substituted or unsubstituted, when substituted R 2 is selected from methyl, trifluoromethyl, methyl ester or ethyl ester; R 3 , R 4 , R 5 , R 6 Each is independently selected from an alkane, a phenyl group or a substituted phenyl group. The present invention has mild reaction conditions, cheap and readily available raw materials, simple reaction operation, high yield, economical and practical, and is environmentally friendly.

Description

Technical Field

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

[0002] In recent decades, research on the application of hypervalent iodine reagents has rapidly advanced. Compared to heavy metal oxidants with similar reactivity, organic hypervalent iodine reagents are green, mild, highly efficient, and versatile oxidants, suitable for the construction of carbon-carbon, carbon-oxygen, carbon-nitrogen, and carbon-halogen bonds. They are also easy to prepare and operate. The use of hypervalent iodine reagents can reduce the toxicity and environmental pollution associated with traditional metal oxidants; therefore, they are gaining increasing attention in pharmaceutical synthesis.

[0003] Although chemists have achieved many results in chiral hypervalent iodine catalysis, there are still many challenges, such as: 1) The types of chiral hypervalent iodine catalysts with more flexible conformations are limited, and flexible aryl iodine catalysts with multiple chiral centers can achieve the regulation of the size of the catalyst chiral pocket and achieve better catalytic activity. 2) Chiral hypervalent iodine catalysts containing multiple hydrogen bonds have not been reported, and hydrogen bond strengthening strategies are the key to achieving the control of the catalyst's activity and stereoselectivity for reaction substrates. 3) The industrial production of chiral iodine catalysts is difficult to achieve. Since chiral aryl iodine catalysts with C2 symmetric structures basically rely on the Mitsunobu reaction, triphenylphosphine and hydrazine generated by the side reaction are difficult to remove. The maximum yield in the reported literature is only 20g, and no larger quantities have been reported. Therefore, the design and synthesis of a new conformationally flexible catalyst library that is easily accessible and highly reactive is a very important research. Summary of the Invention

[0004] The present invention overcomes many shortcomings of traditional methods for constructing chiral aryl iodide catalysts, innovatively develops a method for synthesizing green, low-toxic, and environmentally friendly chiral aryl iodide catalysts using chloramphenicol as a chiral source under mild conditions.

[0005] A flexible chiral aryl iodide catalyst using chloramphenicol as a chiral source, the structural formula of which is shown in formula (10),

[0006]

[0007] where R 1is selected from hydroxy protecting groups including trimethylsilyl, triethylsilyl, triethylpropylsilyl, diethylisopropylsilyl, dimethyl-tert-butylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, acetyl, trifluoroacetyl, trichloroacetyl, tert-butylacetyl, benzoyl or substituted phenyl, wherein the substituent on the substituted phenyl is monosubstituted or polysubstituted, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro; the substituent R 2 Substituted or unsubstituted, when substituted R 2 is selected from methyl, trifluoromethyl, methyl ester or ethyl ester; R 3 , R 4 , R 5 and R 6 Each is independently selected from an alkane, a phenyl group or a substituted phenyl group, the substituent on the substituted phenyl group is monosubstituted or polysubstituted, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro.

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

[0009] 1) The amino group of chloramphenicol represented by formula (1) is protected by di-tert-butyl dicarbonate and then recrystallized by solvent to obtain the intermediate represented by formula (2);

[0010] 2) reacting the intermediate represented by formula (2) with chlorosilane in a solvent under the action of a base to generate an intermediate represented by formula (3);

[0011] 3) reacting the intermediate represented by formula (3) with thionyl chloride in the presence of imidazole and a base to generate the intermediate represented by formula (4);

[0012] 4) reacting the intermediate represented by formula (4) in a solvent under the action of an oxidant and a catalyst, and obtaining the intermediate represented by formula (5) by recrystallization;

[0013] 5) reacting the intermediate represented by formula (5) and the 2-iodobenzene derivative represented by formula (6) under the action of a base to generate the intermediate represented by formula (7);

[0014] 6) removing the protecting group of the intermediate represented by formula (7) in a solvent under the action of an acid to generate the intermediate represented by formula (8);

[0015] 7) reacting the intermediate represented by formula (8) with an acyl chloride, sulfonamide, isocyanate or isothiocyanate in the presence of a base, and recrystallizing from a solvent to obtain a chiral aryl iodide catalyst represented by formula (9);

[0016] 8) removing the silicon group from the intermediate represented by formula (9) under the action of tetrabutylammonium fluoride to obtain an intermediate, which is then reacted with an acyl chloride, sulfonamide, isocyanate or isothiocyanate, and recrystallized from a solvent to obtain a chiral aryl iodide catalyst represented by formula (10).

[0017] The reaction process is as follows:

[0018]

[0019]

[0020] where R 1 is selected from hydroxy protecting groups including trimethylsilyl, triethylsilyl, triethylpropylsilyl, diethylisopropylsilyl, dimethyl-tert-butylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, acetyl, trifluoroacetyl, trichloroacetyl, tert-butylacetyl, benzoyl or substituted phenyl, wherein the substituent on the substituted phenyl is monosubstituted or polysubstituted, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro; the substituent R 2 and R 12 Substituted or unsubstituted, when substituted R 2 and R 12 is selected from methyl, trifluoromethyl, methyl ester or ethyl ester; R 3 , R 4 , R 5 , R 6 Each is independently selected from an alkane, a phenyl group or a substituted phenyl group, the substituent on the substituted phenyl group is monosubstituted or polysubstituted, the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro, R 8 , R 9 , R 10 and R 11 Each is independently selected from an alkane, a phenyl group or a substituted phenyl group, the substituent on the substituted phenyl group is monosubstituted or polysubstituted, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro.

[0021] Furthermore, the amount of di-tert-butyl dicarbonate used in step 1) is 1.0-10.0 equivalents of the compound represented by formula (1), the solvent used for recrystallization of the intermediate (2) is ethyl acetate, methanol or diethyl ether, the reaction temperature is -20-0°C, and the reaction time is 2-7h.

[0022] Furthermore, in step 2), the chlorosilane is tert-butyldiphenylchlorosilane, tert-butyldimethylchlorosilane, trimethylchlorosilane, triethylchlorosilane, triisopropylchlorosilane, dimethylisopropylchlorosilane or diethylisopropylchlorosilane, and the amount of the chlorosilane is 1.0-5.0 equivalents of the intermediate represented by formula (2). The solvent is dichloromethane, dichloroethane, chloroform, tetrahydrofuran or N,N-dimethylformamide. The reaction temperature is -20-0°C and the reaction time is 2-5h.

[0023] Furthermore, the amount of thionyl chloride used in step 3) is 1.0-5.0 equivalents of the intermediate represented by formula (3), the amount of imidazole used is 1.0-20.0 equivalents of the intermediate represented by formula (3), the base is triethylamine or N,N-diisopropylethylamine, the amount of the base used is 2.0-10.0 equivalents of the intermediate represented by formula (3), the reaction temperature is -70-0°C, and the reaction time is 2-5h.

[0024] Furthermore, the oxidant in step 4) is sodium periodate, and the amount of the oxidant is 1.0-5.0 equivalents of the intermediate represented by formula (4); the catalyst is hydrated ruthenium trichloride, and the amount of the catalyst is 1-30 mol% of the intermediate represented by formula (4); the solvent is acetonitrile and water or dichloromethane and water, and the amount of the solvent is 1:1; the reaction temperature is 0-30 ° C, and the reaction time is 2-6 h.

[0025] Furthermore, in step 5), the amount of the intermediate represented by formula (5) is 2.0-10.0 equivalents of the 2-iodobenzene derivative represented by formula (6), the base is sodium hydride, the amount of the base is 2.0.-10.0 equivalents of the 2-iodobenzene derivative represented by formula (6), the reaction temperature is -20-0°C, and the reaction time is 2-6h.

[0026] Furthermore, in step 6), the solvent is dichloromethane, dichloroethane or chloroform, the acid is trifluoroacetic acid, hydrochloric acid or sulfuric acid, the amount of acid to solvent is 1:3-1:10, the reaction temperature is -20-0°C, and the reaction time is 1-5h.

[0027] Furthermore, in step 7), the amount of the acid chloride, sulfonamide, isocyanate or isothiocyanate used is 2.0-10.0 equivalents of the intermediate represented by formula (8), the base is triethylamine, and the amount of the base used is 2.0-10.0 equivalents of the intermediate represented by formula (8), the recrystallization solvent is tetrahydrofuran, methyl tert-butyl ether or dioxane, the reaction temperature is -20-50°C, and the reaction time is 1-8h; in step 8), the amount of tetrabutylammonium fluoride used is 1.0-20.0 equivalents of the compound represented by formula (9), the amount of the acid chloride, sulfonamide, isocyanate or isothiocyanate used is 2.0-10.0 equivalents of the intermediate represented by formula (9), the base is triethylamine, and the amount of the base used is 2.0-10.0 equivalents of the compound represented by formula (9).

[0028] The invention discloses an application of a flexible chiral aryl iodide catalyst using chloramphenicol as a chiral source. 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.

[0029] Application of the present invention:

[0030] The catalyst disclosed in the present invention using chloramphenicol as a chiral source can be used to catalyze the 1-naphthol derivative shown in formula (11) to generate the product shown in formula (12) through a one-step reaction. It can also be used to catalyze the malonamide derivative shown in formula (13) to generate the product shown in formula (14) through a one-step reaction. It can also be used for the α-fluorination of dicarbonyl compounds (15) to obtain product (16).

[0031]

[0032] The beneficial effects of the present invention are:

[0033] 1) Using chloramphenicol as a chiral source, a multichiral flexible aryl iodide catalyst was designed and synthesized;

[0034] 2) The compound preparation of the present invention achieves a 100-gram scale reaction, is practical, has broad application prospects, and is suitable for industrial-scale production.

[0035] 3) The present invention has high reaction efficiency, high yield, simple and stable preparation, no irritating odor, and mild reaction conditions. DETAILED DESCRIPTION

[0036] The present invention is further described in detail below in conjunction with the following specific examples, and the protection content of the present invention is not limited to the following examples. 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 are protected by the appended claims. The process, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are common knowledge and common common sense in the art, and the present invention has no special restrictions. The data given in the following examples include specific operations and reaction conditions and products. Product purity is identified by nuclear magnetic resonance.

[0037] A synthesis reaction of a chiral aryl iodide catalyst using chloramphenicol as a chiral source, the reaction process is as follows:

[0038] Example 1

[0039] Synthesis of tert-butyl (1S,2S)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-ylcarbamate:

[0040]

[0041] 1S,2S-2-amino-1-(4-nitrophenyl)propane-1,3-diol (70 g, 330 mmol, 1.0 equiv.) and tetrahydrofuran (500 mL) were added to a three-necked flask, followed by the dropwise addition of di-tert-butyl dicarbonate (75.6 g, 347 mmol, 1.05 equiv.) at room temperature. After reacting at room temperature for 3 h, the solvent was removed under reduced pressure and the product was recrystallized from ethyl acetate to obtain product 2 (93.6 g, 93%).

[0042] Example 2

[0043] Synthesis of tert-butyl (4S,5R)-4-((tert-butyldiphenylsilyl)oxy)methyl)-5-(4-nitrophenyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide:

[0044]

[0045] In a three-necked flask, tert-butyl (1S,2S)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-ylcarbamate (2) (93.6 g, 307 mmol, 1.0 equiv.), imidazole (27.1 g, 399 mmol, 1.3 equiv.) and dichloromethane (500 mL) were added, and then tert-butyldiphenylsilyl chloride (88.55 g, 322 mmol, 1.05 equiv.) was added dropwise at 0°C. After reacting for 2 h, the reaction was quenched with water, extracted with dichloromethane, and the organic phase was separated. The solvent was removed under reduced pressure to obtain a crude product 3 (210 g).

[0046] Under nitrogen protection, the crude product tert-butyl ((1S, 2S)-3-(tert-butyldiphenylsilyloxy)-1-hydroxy-1-(4-nitrophenyl)propyl-2-yl)carbamate (3) (210 g) imidazole (67.0 g, 982 mmol, 3.0 equiv.) and dichloromethane (500 mL) were added to a three-necked flask, and then triethylamine (74.5 g, 737 mmol, 2.4 equiv.) was added dropwise at -40°C. After the addition was complete, thionyl chloride (44.0 g, 369 mmol, 1.2 equiv.) was added dropwise and reacted for 3 h. The reaction was quenched with water, extracted with dichloromethane, and the organic phase was separated. The solvent was removed under reduced pressure to obtain a crude product 4 (253 g).

[0047] Under nitrogen protection, the crude product (4S,5R)-4-((tert-butyldiphenylsilyl)oxy)methyl)-5-(4-nitrophenyl)-1,2,3-oxathiazolidine-3-carboxylic acid tert-butyl ester 2-oxide (4) (253 g) was added to a three-necked flask and dissolved in acetonitrile and water (1:1) (450 mL). Ruthenium trichloride trihydrate (635 mg, 1 mol%) and sodium periodate (73 g, 337 mmol, 1.1 equiv.) were added in sequence. The mixture was reacted at 20°C for 4 h, extracted with ethyl acetate, and the organic phase was separated. After removing the solvent under reduced pressure, methanol was added to precipitate the pure product 5, a total of 159 g, with a three-step yield of 86%.

[0048] 1 H NMR (400MHz, CDCl3) δ8.25–8.19(m,2H),7.70(dt,J=6.7,1.5Hz,2H),7.65(dt,J=6.5,1.6Hz,2H),7.5 2–7.41(m,8H),5.85(d,J=5.7Hz,1H),4.30–4.22(m,2H),3.78–3.66(m,1H),1.53(s,9H),1.13(s,9H); 13 C NMR (100MHz, CDCl3) δ148.7,148.2,141.1,135.8,135.7,132.5,132.2,130.4 ,130.3,128.2,128.1,127.7,124.3,86.1,79.1,64.6,59.6,28.0,26.9,19.4.

[0049] HRMS(ESI):calc.for[C 30 H 36 N2O8SSi+Na] + 635.1854; found 635.1846.

[0050] Example 3

[0051] Synthesis of di-tert-butyl((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy))bis(3-(tert-butyldiphenylsilyl)oxy)-1-(4-nitrophenyl)propane-1,2-diyl))dicarbamate:

[0052]

[0053] Under nitrogen protection, 2-iodobenzene-1,3-diol (6) (30.5 g, 130 mmol, 1 equiv.) and N,N-dimethylformamide (300 mL) were added to a three-necked flask. Sodium hydride (mass concentration 60%) (10.66 g, 266 mmol, 2.05 equiv.) was slowly added at 0°C. After stirring for 30 min, (4S,5R)-4-((tert-butyldiphenylsilyl)oxy)methyl)-5-(4-nitrophenyl)-1,2,3-oxathiazolidine-3-carboxylic acid tert-butyl ester 2,2-dioxide (5) (159 g, 261 mmol, 2.01 equiv.) was slowly added dropwise. The mixture was stirred for 4 h until the reaction of the raw materials was complete. After the reaction was completed, hydrochloric acid was used to quench the reaction, ethyl acetate was added for extraction, the organic phase was separated, the solvent was removed under reduced pressure, and the mixture was recrystallized from ethyl acetate and water to obtain a paste-like yellow solid. A total of 207 g of crude product was obtained.

[0054] 1 H NMR(400MHz, CDCl3)δ8.09(d,J=8.3Hz,4H),7.57–7.44(m,12H),7.36–7.31(m,2 H),7.29–7.23(m,6H),7.20–7.12(m,4H),6.79(t,J=8.3Hz,1H),6.01(d,J=8.3H z,2H),5.40(d,J=6.4Hz,2H),4.97(d,J=9.1Hz,2H),4.26(dd,J=10.6,5.1Hz,2H ),4.21–4.09(m,2H),3.79(dd,J=10.6,3.2Hz,2H),1.27(s,18H),0.98(s,18H); 13 C NMR (100MHz, CDCl3) δ157.0,155.1,147.7,145.3,135.6,135.5,132.9,132.8,130.0 ,129.9,129.7,127.9,127.8,123.7,106.5,79.9,79.5,62.3,57.1,28.3,26.9,19.3.

[0055] HRMS(ESI):calc.for[C 66 H 77 IN4O 12 Si2+Na] + 1323.4013; found 1323.4023. Example 4

[0056] Synthesis of 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-2-amine):

[0057]

[0058] The crude product (7) (207 g) and dichloromethane (200 mL) were added to a three-necked flask, and trifluoroacetic acid (50 mL) was slowly added at 0°C. After stirring for 2 h, the mixture was slowly quenched with NaOH. Dichloromethane was added for extraction, and the organic phase was separated. After removing the solvent under reduced pressure, the mixture was recrystallized from methanol to obtain an off-white solid. A total of 106 g of the product was obtained, with a two-step yield of 74%.

[0059] 1 H NMR(400MHz, CDCl3)δ8.06(d,J=8.7Hz,4H),7.57–7.48(m,8H),7.45–7.39(m,4H),7.35–7.24(m,8H),7.21–7.16(m,4H),6.73(t,J=8.3Hz,1H ),5.97(d,J=8.3Hz,2H),5.31(d,J=5.8Hz,2H),3.88(dd,J=10.2,6.1Hz,2H),3.61(dd,J=10.2,5.0Hz,2H),3.37–3.28(m,2H),0.96(s,18H); 13 C NMR (100MHz, CDCl3) δ156.9,147.8,145.3,135.7,135.6,133.1,133.1,130.0,129 .9,129.7,128.1,128.0,127.9,123.9,106.5,80.9,79.8,64.9,57.8,27.0,19.4.

[0060] HRMS(ESI):calc.for[C 56 H 61 IN4O8Si2+H] + 1101.3145; found 1101.3154.

[0061] Example 5

[0062] Synthesis of N,N'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-1,2-diyl))bis(4-nitrobenzamide):

[0063]

[0064] Under nitrogen atmosphere, 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (5.0 mL) were added to a dry schlenk tube, followed by the dropwise addition of 4-nitrobenzoyl chloride (408.2 mg, 2.2 mmol, 2.2 equiv.) at 0°C. After 2 h of reaction, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, the solvent was removed under reduced pressure, and the product was purified by recrystallization from methanol to obtain Cat-1 (1.3 g, 93%).

[0065] 1 H NMR (400MHz, CDCl3) δ8.16(d,J=8.5Hz,4H),8.03(d,J=8.4Hz,4H),7.64(d,J=8.6Hz,4 H),7.50–7.41(m,12H),7.34–7.27(m,4H),7.23–7.15(m,8H),6.77(t,J=8.3Hz,1H),6. 60(d,J=8.5Hz,2H),5.98(d,J=8.4Hz,2H),5.49(d,J=5.5Hz,2H),4.65(dtd,J=9.2,5.9 ,3.4Hz,2H),4.37(dd,J=11.0,6.3Hz,2H),3.84(dd,J=11.1,3.4Hz,2H),0.92(s,18H); 13 C NMR (100MHz, CDCl3) δ165.2,157.2,149.8,147.9,144.4,139.3,135.6,135.6,132.6,130.2, 130.1,128.1,128.1,128.0,127.4,124.0,123.9,107.1,79.9,79.4,61.7,56.6,26.9,19.3.

[0066] HRMS(ESI):calc.for[C 70 H 67 IN6O 14 Si2+Na] + 1421.3191; found 1421.3219.

[0067] Example 6

[0068] Synthesis of N,N'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-1,2-diyl))bis(2,2-dimethylpropionamide):

[0069]

[0070] Under nitrogen atmosphere, 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (5.0 mL) were added to a dry schlenk tube, followed by dropwise addition of pivaloyl chloride (266.2 mg, 2.2 mmol, 2.2 equiv.) at 0 ° C. After 2 h of reaction, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, the solvent was removed under reduced pressure, and the product Cat-2 (1.08 g, 85%) was obtained by slurrying with ethyl acetate and petroleum ether.

[0071] 1 H NMR(400MHz, CDCl3)δ8.13(d,J=8.7Hz,4H),7.57–7.48(m,12H),7.41–7.37(m,2 H),7.36–7.28(m,6H),7.25–7.19(m,4H),6.84(t,J=8.3Hz,1H),6.23(d,J=8.3H z,2H),6.06(d,J=8.4Hz,2H),5.48(d,J=6.2Hz,2H),4.54–4.45(m,2H),4.35(dd ,J=10.8,5.4Hz,2H),3.75(dd,J=10.8,3.3Hz,2H),1.03(s,18H),1.02(s,18H); 13 C NMR (100MHz, CDCl3) δ178.2,157.5,147.8,145.2,135.6,135.5,132.7,132.6,130.1,13 0.0,130.0,128.0,128.0,127.7,123.8,106.8,79.5,61.9,55.7,38.8,27.5,26.9,19.3.

[0072] HRMS(ESI):calc.for[C 66 H 77 IN4O 10 Si2+H]+ 1269.4296; found 1269.4279.

[0073] Example 7

[0074] Synthesis of N,N'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-1,2-diyl))diethylamide:

[0075]

[0076] Under nitrogen atmosphere, 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (5.0 mL) were added to a dry schlenk tube, followed by the dropwise addition of acetyl chloride (173.0 mg, 2.2 mmol, 2.2 equiv.) at 0 ° C. After 2 h of reaction, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, the solvent was removed under reduced pressure, and the product Cat-4 (1.065 g, 90%) was purified by recrystallization from methanol.

[0077] 1 H NMR(400MHz, CDCl3)δ8.04(d,J=8.6Hz,4H),7.50–7.45(m,8H),7.41(d,J=8.5Hz ,4H),7.34–7.27(m,4H),7.26–7.17(m,8H),6.75(t,J=8.3Hz,1H),5.95(d,J=8. 4Hz,2H),5.80(d,J=8.7Hz,2H),5.38(d,J=5.4Hz,2H),4.45–4.37(m,2H),4.22( dd,J=11.0,6.2Hz,2H),3.72(dd,J=10.9,3.3Hz,2H),1.76(s,6H),0.94(s,18H); 13 C NMR (100MHz, CDCl3) δ169.9,157.2,147.7,144.9,135.6,132.9,132.8,130.1,130.0 ,130.0,128.0,128.0,127.5,123.9,106.8,79.7,79.5,61.8,56.0,26.9,23.3,19.3.

[0078] HRMS(ESI):calc.for[C 60 H 65 IN4O 10 Si2+Na] + 1185.3362found 1185.3378.

[0079] Example 8

[0080] Synthesis of N,N'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-1,2-diyl))bis(4-methylbenzamide):

[0081]

[0082] Under nitrogen atmosphere, 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (5.0 mL) were added to a dry schlenk tube, followed by dropwise addition of 4-methylbenzoyl chloride (341.2 mg, 2.2 mmol, 2.2 equiv.) at 0°C. After reacting for 2 h, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, the solvent was removed under reduced pressure, and the product was purified by recrystallization from methanol to obtain Cat-5 (1.097 g, 82%).

[0083] 1 H NMR (400MHz, CDCl3) δ7.98 (d, J=8.4Hz, 4H), 7.51–7.40 (m, 16H), 7.31–7.24 (m,4H),7.21–7.12(m,12H),6.71(t,J=8.3Hz,1H),6.57(d,J=8.5Hz,2H),5 .94(d,J=8.4Hz,2H),5.47(d,J=5.6Hz,2H),4.69–4.59(m,2H),4.34(dd,J= 10.9,6.1Hz,2H),3.82(dd,J=10.9,3.4Hz,2H),2.30(s,6H),0.91(s,18H); 13C NMR (100MHz, CDCl3) δ167.0,157.2,147.7,144.9,142.5,135.6,135.5,132.8,132.7,131.0,13 0.0,130.0,129.4,127.9,127.4,126.9,123.9,106.9,80.0,79.6,61.9,56.3,26.9,21.5,19.2.

[0084] HRMS(ESI):calc.for[C 60 H 65 IN4O 10 Si2+Na] + 1359.3802 found 1359.3774. Example 9

[0085] Synthesis of N,N'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-1,2-diyl))bis(4-trifluoromethylbenzamide):

[0086]

[0087] Under nitrogen atmosphere, 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (5.0 mL) were added to a dry schlenk tube, followed by the dropwise addition of 4-trifluoromethylbenzoyl chloride (459.8 mg, 2.2 mmol, 2.2 equiv.) at 0 ° C. After reacting for 2 h, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, the solvent was removed under reduced pressure, and the product was purified by recrystallization from methanol to obtain Cat-6 (1.127 g, 78%).

[0088] 1H NMR(400MHz,Chloroform-d)δ8.02(d,J=8.7Hz,4H),7.65–7.55(m,8H),7.50– 7.40(m,12H),7.33–7.25(m,4H),7.22–7.14(m,8H),6.76(t,J=8.3Hz,1H),6.5 8(d,J=8.5Hz,2H),5.97(d,J=8.4Hz,2H),5.48(d,J=5.5Hz,2H),4.71–4.60(m, 2H), 4.36 (dd, J=11.0, 6.2Hz, 2H), 3.83 (dd, J=11.0, 3.4Hz, 2H), 0.93 (s, 18H); 13 C NMR (100MHz, CDCl3) δ165.9,157.2,147.9,144.6,137.1,135.6,135.6,133.6(q, 2 J C-F =32.7Hz),132.7,132.7,130.2,130.1,128.0,128.0,127.4,125.8(q, 3 J C-F =3.7Hz),124.0,123.7(q, 1 J C-F =272.5Hz),107.1,80.0,79.5,61.8,56.5,26.9,19.3. 19 F NMR (376MHz,CDCl3)δ-62.86.

[0089] HRMS(ESI):calc.for[C 72 H 67 F6IN4O 10 Si2+Na] + 1467.3237 found 1467.3234. Example 10

[0090] Synthesis of N,N'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-1,2-diyl))bis(2,4,6-trimethylbenzamide):

[0091]

[0092] Under nitrogen atmosphere, 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (5.0 mL) were added to a dry schlenk tube, followed by the dropwise addition of 2,4,6-trimethylbenzoyl chloride (402.6 mg, 2.2 mmol, 2.2 equiv.) at 0°C. After 2 h of reaction, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, the solvent was removed under reduced pressure, and the product was purified by recrystallization from methanol to obtain Cat-7 (1.12 g, 86%).

[0093] 1 H NMR (400MHz, CDCl3) δ8.09 (d, J=8.8Hz, 4H), 7.53–7.40 (m, 12H), 7.30–7.24 (m ,4H),7.18–7.11(m,8H),6.78(t,J=8.3Hz,1H),6.73(s,4H),6.02(dd,J=8.2, 2.3Hz,4H),5.69(d,J=4.9Hz,2H),4.71–4.59(m,2H),4.30(dd,J=11.2,6.8Hz ,2H),3.81(dd,J=11.1,3.1Hz,2H),2.22(s,6H),1.88(s,12H),0.94(s,18H); 13 C NMR (100MHz, CDCl3) δ170.7,157.1,147.9,144.7,138.9,135.5,134.2,134.2,132.7,132.5,130.1 ,130.0,129.9,128.3,127.9,127.7,124.0,106.5,79.5,79.3,61.7,57.0,26.9,21.1,19.2,18.9.

[0094] HRMS(ESI):calc.for[C 76 H 81 IN4O 10 Si2+Na] + 1415.4428 found 1415.4434. Example 11

[0095] Synthesis of N,N'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-1,2-diyl))bis(4-methoxybenzamide):

[0096]

[0097] Under nitrogen atmosphere, 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (5.0 mL) were added to a dry schlenk tube, followed by the dropwise addition of 4-methoxybenzoyl chloride (376.2 mg, 2.2 mmol, 2.2 equiv.) at 0°C. After 2 h of reaction, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, the solvent was removed under reduced pressure, and the product was purified by recrystallization from methanol to obtain Cat-8 (1.231 g, 90%).

[0098] 1 H NMR(400MHz, CDCl3)δ8.10(d,J=8.3Hz,4H),7.61(d,J=8.4Hz,4H),7.58–7.50(m,12 H),7.42–7.35(m,4H),7.31–7.24(m,8H),6.93(d,J=8.3Hz,4H),6.80(t,J=8.3Hz,1 H),6.56(d,J=8.2Hz,2H),6.02(d,J=8.3Hz,2H),5.55(d,J=5.2Hz,2H),4.76–4.66( m,2H),4.42(dd,J=10.8,6.0Hz,2H),3.93–3.88(m,2H),3.88(s,6H),1.01(s,18H); 13 C NMR (100MHz, CDCl3) δ166.7,162.6,157.3,147.7,145.0,135.7,135.6,132.9,132.8,130.1,13 0.0,128.8,128.0,127.4,126.1,124.0,114.0,107.0,80.2,79.6,61.9,56.4,55.6,26.9,19.3.

[0099] HRMS(ESI):calc.for[C 72 H 73 IN4O12 Si2+Na] + 1369.3886found 1369.3877.

[0100] Example 12

[0101] Synthesis of N,N'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-1,2-diyl))bis(benzamide):

[0102]

[0103] Under nitrogen atmosphere, 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (5.0 mL) were added to a dry schlenk tube, followed by the dropwise addition of benzoyl chloride (310.4 mg, 2.2 mmol, 2.2 equiv.) at 0°C. After 2 h of reaction, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, the solvent was removed under reduced pressure, and the product was purified by recrystallization from methanol to obtain Cat-9 (1.139 g, 87%).

[0104] 1 H NMR(400MHz, CDCl3)δ8.01(d,J=8.8Hz,4H),7.56–7.52(m,4H),7.49–7.41(m,14H ),7.38–7.33(m,4H),7.32–7.25(m,4H),7.22–7.14(m,8H),6.73(t,J=8.3Hz,1H) ,6.55(d,J=8.5Hz,2H),5.94(d,J=8.4Hz,2H),5.47(d,J=5.5Hz,2H),4.68–4.60( m,2H),4.34(dd,J=10.9,6.1Hz,2H),3.81(dd,J=10.9,3.4Hz,2H),0.92(s,18H); 13C NMR (100MHz, CDCl3) δ167.2,157.3,147.8,144.9,135.7,135.6,133.9,132.8,132.8,132.0, 130.1,130.1,128.8,128.0,127.4,127.0,124.0,107.0,80.0,79.6,61.9,56.4,26.9,19.3.

[0105] HRMS(ESI):calc.for[C 70 H 69 IN4O 10 Si2+H] + 1309.3670found 1309.3664.

[0106] Example 13

[0107] Synthesis of 1,1'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyl)oxy)-1-(4-nitrophenyl)propane-1,2-diyl)bis(3-p-tolyl)urea):

[0108]

[0109] Under nitrogen atmosphere, a dry Schlenk tube was charged with 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.), DMAP (24.4 mg, 0.2 mmol, 0.2 equiv.) and anhydrous DCM (5.0 mL). Then, p-toluene isocyanate (293.0 mg, 2.2 mmol, 2.2 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. The product Cat-10 (1.19 g, 86%) was purified by recrystallization from methanol.

[0110] 1H NMR(400MHz, CDCl3) δ7.99(d,J=8.4Hz,4H),7.43–7.37(m,8H),7.34(d,J=7.4Hz,4H),7.30 –7.26(m,2H),7.20–7.15(m,6H),7.08–7.00(m,8H),6.93(d,4H),6.70(t,J=8.3Hz,1H),6.5 2(s,2H),5.92(d,J=8.4Hz,2H),5.36(d,J=6.4Hz,2H),5.27(d,J=8.5Hz,2H),4.39–4.31(m, 2H), 4.22 (dd, J=10.7, 5.0Hz, 2H), 3.68 (dd, J=10.8, 3.2Hz, 2H), 2.22 (s, 6H), 0.82 (s, 18H); 13 C NMR (100MHz, CDCl3) δ157.1,155.7,147.7,145.4,135.5,135.5,135.2,134.9,132.7,132.6,130.3,130.0,1 29.8,127.9,127.9,127.8,123.8,123.3,106.5,79.3,79.3,77.5,77.2,76.8,62.3,56.6,26.8,21.0,19.2.

[0111] HRMS(ESI):calc.for[C 72 H 75 IN6O 10 Si2+H] + 1367.4201found 1367.4210.

[0112] Example 14

[0113] Synthesis of 1,1'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyl)oxy)-1-(4-nitrophenyl)propane-1,2-diyl)bis(3-m-tolyl)urea):

[0114]

[0115] Under nitrogen atmosphere, a dry Schlenk tube was charged with 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.), DMAP (24.4 mg, 0.2 mmol, 0.2 equiv.) and anhydrous DCM (5.0 mL). Then, m-toluene isocyanate (293.0 mg, 2.2 mmol, 2.2 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. The product Cat-11 (1.135 g, 83%) was obtained by recrystallization from methanol.

[0116] 1 H NMR (400MHz, CDCl3) δ8.06 (d, J = 8.4Hz, 4H), 7.56–7.47 (m, 12H), 7.40–7.35 (m, 2H), 7.35–7 .26(m,6H),7.23–7.16(m,6H),7.00(s,2H),6.98–6.92(m,4H),6.82(t,J=8.3Hz,1H),6.78 (s,2H),6.05(d,J=8.5Hz,2H),5.53(d,J=6.0Hz,2H),5.48(d,J=8.4Hz,2H),4.54–4.45(m, 2H), 4.35 (dd, J=10.8, 5.4Hz, 2H), 3.84 (dd, J=10.9, 3.3Hz, 2H), 2.30 (s, 6H), 0.96 (s, 18H); 13 C NMR (100MHz, CDCl3) δ157.1,155.5,147.6,145.3,139.6,137.7,135.5,135.5,132.8,132.7,130.0,129.9 ,129.4,127.9,127.9,127.7,125.7,123.8,123.0,119.3,106.5,79.5,79.2,62.2,56.7,26.8,21.5,19.2.

[0117] HRMS(ESI):calc.for[C 72 H 75 IN6O 10 Si2+H] + 1367.4201found 1367.4189.

[0118] Example 15

[0119] Synthesis of N,N'-((1R,1'R,2S,2'S)-((2-iodo-1,3-phenylene)bis(oxy)bis(3-(tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propane-1,2-diyl))bis(4-methylbenzenesulfonamide):

[0120]

[0121] Under nitrogen atmosphere, 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) and anhydrous DCM (5.0 mL) were added to a dry schlenk tube, followed by the dropwise addition of p-toluenesulfonyl chloride (420.2 mg, 2.2 mmol, 2.2 equiv.) at 0°C. After 2 h of reaction, the reaction was quenched with water and extracted with dichloromethane. The organic phase was separated, the solvent was removed under reduced pressure, and the product was purified by recrystallization from ethyl acetate and petroleum ether to obtain Cat-12 (1.323 g, 94%).

[0122] 1 H NMR(400MHz, CDCl3) δ7.86(d,J=8.5Hz,4H),7.40–7.17(m,18H),7.15–7.05(m,6H),7.00–6.90(m,4H),6.86(d,J=8.1Hz,4H),6.64(t ,J=8.3Hz,1H),5.88(d,J=8.5Hz,2H),5.39–5.21(m,4H),4.16(dd,J=10.6,3.6Hz,2H),3.73–3.51(m,4H),2.12(s,6H),0.80(s,18H); 13 C NMR (100MHz, CDCl3) δ156.5,147.6,144.7,143.5,137.2,135.4,135.3,132.3,129.9,129.7 ,129.5,127.9,127.8,127.7,126.7,123.6,106.4,79.2,78.1,62.1,60.1,26.8,21.3,19.1.

[0123] HRMS(ESI):calc.for[C 70 H 73 IN4O 12 S2Si2+H]+ 1409.3328found 1409.3333.

[0124] Example 16

[0125] Synthesis of (2S,2'S,3R,3'R)-((2-iodo-1,3-phenylene)bis(3-(4-nitrophenyl)-2-(2,4,6-trimethylbenzamido)propane-3,1-diyl)bis(2,4,6-trimethylbenzoate):

[0126]

[0127] Under nitrogen, a dry Schlenk tube was charged with 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.), and anhydrous DCM (5.0 mL). 2,4,6-trimethylbenzoyl chloride (402.6 mg, 2.2 mmol, 2.2 equiv.) was then 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, the solvent removed under reduced pressure, and the product was purified by recrystallization from methanol to obtain Cat-7 (1.120 g, 86%).

[0128] Cat-7 was dissolved in tetrahydrofuran (10 mL), followed by the dropwise addition of TBAF (2.5 mL, 1 mol / L in THF). The mixture was stirred at room temperature for 2 h, quenched with water, extracted with ethyl acetate, and the organic phase separated. The solvent was removed under reduced pressure, and the mixture was purified by recrystallization from methanol to afford a white solid. The white solid and triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.) were dissolved in anhydrous DCM (5.0 mL), and 2,4,6-trimethylbenzoyl chloride (402.6 mg, 2.2 mmol, 2.2 equiv.) was slowly added dropwise. After 2 h, the reaction was quenched with water, extracted with dichloromethane, and the organic phase separated. The solvent was removed under reduced pressure, and the mixture was purified by recrystallization from methanol to afford Cat-13 (765.0 mg, 62%).

[0129] 1H NMR (400MHz, CDCl3) δ8.21(d,J=8.8Hz,4H),7.65(d,J=8.8Hz,4H),6.91(t,J=8.3 Hz,1H),6.80(s,4H),6.79(s,4H),6.28(d,J=8.5Hz,2H),6.14(d,J=8.4Hz,2H),5. 76(d,J=4.4Hz,2H),5.01(tt,J=8.3,3.6Hz,2H),4.92(dd,J=11.6,7.1Hz,2H),4. 57(dd,J=11.6,3.9Hz,2H),2.28(s,6H),2.27(s,6H),2.18(s,12H),1.97(s,12H). 13 C NMR (100MHz, CDCl3) δ170.5,169.4,156.9,147.8,143.9,139.9,139.0,135.3,133.9,133.7,130.1,129 .6,128.5,128.3,127.5,124.0,106.8,79.9,79.5,77.5,77.2,76.8,62.2,53.8,21.1,21.0,20.0,18.7.

[0130] HRMS(ESI):calc.for[C 64 H 65 IN4O 12 Si2+H] + 1209.3716 found 1209.3719. Example 17

[0131] Synthesis of (2S,2'S,3R,3'R)-((2-iodo-1,3-phenylene)bis(3-(4-nitrophenyl)-2-(2,4,6-trimethylbenzamido)propane-3,1-diyl)bis(2,4,6-trimethylbenzoate):

[0132]

[0133] Under nitrogen, a dry Schlenk tube was charged with 1R,1'R,2S,2'S-(2-iodo-1,3-phenylene)bis(oxy)bis(3-tert-butyldiphenylsilyloxy)-1-(4-nitrophenyl)propan-2-amine) (1.1 g, 1.0 mmol, 1.0 equiv.), triethylamine (252.8 mg, 2.5 mmol, 2.5 equiv.), and anhydrous DCM (5.0 mL). 2,4,6-tribromobenzoyl chloride (750.0 mg, 2.2 mmol, 2.2 equiv.) was then 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, the solvent removed under reduced pressure, and the product was purified by recrystallization from methanol to obtain the product (1.54 g, 86%).

[0134] The resulting product was dissolved in tetrahydrofuran (10 mL), followed by the dropwise addition of TBAF (2.5 mL, 1 mol / L in THF). The mixture was stirred at room temperature for 2 h, quenched with water, extracted with ethyl acetate, and the organic phase separated. The solvent was removed under reduced pressure, and the mixture was purified by recrystallization from methanol to yield a white solid. The white solid and N,N-diisopropylethylamine (285 mg, 2.5 mmol, 2.5 equiv.) were dissolved in anhydrous DCM (5.0 mL), and triphenylmethyl chloride (612 mg, 2.2 mmol, 2.2 equiv.) was slowly added. After 2 h, the reaction was quenched with water, extracted with dichloromethane, and the organic phase separated. The solvent was removed under reduced pressure, and the mixture was purified by recrystallization from methanol to yield Cat-3 (1.083 g, 70% in two steps).

[0135] 1 H NMR (400MHz, CDCl3) δ8.14(d,J=8.2Hz,4H),7.66(s,4H),7.52(d,J=8.5Hz,4H),7.37–7.31(m,12H),7.23–7.15(m,18H),6.84(t,J=8.3Hz,1 H),6.11(s,2H),6.07(d,J=8.4Hz,2H),5.82(d,J=3.7Hz,2H),4.80–4.72(m,2H),3.84(dd,J=10.4,7.5Hz,2H),3.53(dd,J=10.4,3.6Hz,2H); 13 C NMR (100MHz, CDCl3) δ165.9,157.0,147.8,144.2,143.4,138.1,134.3,130.1,128 .7,128.0,127.5,127.3,124.2,124.1,120.9,106.8,87.4,80.3,79.8,60.7,56.2

[0136] HRMS(ESI):calc.for[C 75 H 55 IBr6N4O 10 Si2+H] + 1790.8080 found 1790.8088. Example 18

[0137] Dearomatization of 1-naphthol derivatives:

[0138]

[0139] Under nitrogen atmosphere, a mixture containing Cat-1 (0.03 mmol, 15 mol%) was added. m 1-Naphthol derivative 11 (0.2 mmol) was added to a Schlenk tube containing CPBA (0.26 mmol, 1.3 equiv.), TFE (10 mmol, 50 equiv.), H₂O (2 mmol, 10 equiv.), and MeNO₂ (3 mL). The reaction mixture was stirred at -10°C for 72 hours. The reaction mixture was quenched with saturated aqueous Na₂S₂O₃ and then NaHCO₃. The organic layer was then extracted with ethyl acetate, washed with brine, dried over anhydrous Na₂SO₄, and purified by silica gel column chromatography to afford product 12 (57% yield, 94% ee).

[0140] 1 H NMR (400MHz, CDCl3) δ7.99 (d, J = 7.7Hz, 1H), 7.68-7.61 (m, 1H), 7.44-7.30 (m, 3H), 7.03-6.88 (m, 4H), 6.03 (d, J = 9.6Hz, 1H), 3.29 (s, 3H); 13 C NMR (100MHz, CDCl3) δ194.1,172.8,144.9,138.3,135.4,129.4,129.3,128.7,128.7,128.4,128.1,127.8,123.5,123.1,109.0,64.5,27.0.

[0141] HRMS(ESI):calc.for[C 18 H 13 N2O2+H] + 276.1025found 276.1020.

[0142] Optical Rotation:[α] 25 D-4.2(c=1,CHCl3).

[0143] Example 19

[0144] Cross-coupling of malonamide compounds:

[0145]

[0146] Under nitrogen atmosphere, a mixture containing Cat-2 (0.03 mmol, 15 mol%) was added. m To a Schlenk tube containing CPBA (0.52 mmol, 2.6 equiv.), TFA (0.6 mmol, 3 equiv.), H₂O (0.6 mmol, 3 equiv.), and MeCN (3 mL) was added malonamide derivative 13 (0.2 mmol). The reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was quenched with saturated aqueous Na₂S₂O₃ and then NaHCO₃. The organic layer was then extracted with ethyl acetate, washed with brine, dried over anhydrous Na₂SO₄, and purified by silica gel column chromatography to afford product 14 (72% yield, 90% ee).

[0147] 1 H NMR (400MHz, CDCl3) δ7.38(t,J=7.6Hz,2H),7.04(t,J=7.6Hz,2H),6.96(d,J=7.8Hz,2H),6.88(d,J=7.4Hz,2H),3.30(s,6H); 13 C NMR (100MHz, CDCl3) δ172.2,145.4,129.6,127.9,123.9,123.3,108.8,62.3,27.0.

[0148] HRMS(ESI):calc.for[C 17 H 14 N2O2+H] + 279.1134found 279.1130.

[0149] Optical Rotation:[α] 25 D -71(c=0.5,CHCl3).

[0150] Example 20

[0151] α-Fluorination of dicarbonyl compounds:

[0152]

[0153] Under nitrogen atmosphere, a mixture containing Cat-3 (0.03 mmol, 15 mol%) was added. m To a Teflon tube containing CPBA (0.3 mmol, 1.5 equiv.), Et3N·3HF (10 equiv.), and chloroform (10 mL) was added the dicarbonyl compound 15 (0.2 mmol). The reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was quenched sequentially with saturated aqueous Na2S2O3 and then NaHCO3. The organic layer was then extracted with dichloromethane, washed with brine, dried over anhydrous Na2SO4, and purified by silica gel column chromatography to afford the α-fluorinated product 16 (54% yield, 85% ee).

[0154] 1 H NMR (400MHz, CDCl3) δ7.80(d,J=7.7Hz,1H),7.69(t,J=7.5Hz,1H),7.50(d,J=7.7Hz,1H),7.44(t,J=7.8Hz,1H ), 4.25 (q, J = 7.1Hz, 2H), 3.78 (dd, J = 17.7, 11.5Hz, 1H), 3.41 (dd, J = 23.4, 17.7Hz, 1H), 1.22 (t, J = 7.1Hz, 3H); 13 C NMR(100MHz,CDCl3)δ195.24(d, 2 J C-F =18.2Hz),167.16(d, 2 J C-F =27.9Hz),150.84(d, 3 J C-F =3.6Hz),136.66,133.03,128.48,126.52,125.33,94.36(d, 1 J C-F =201.0Hz),62.41,38.08(d, 2 J C-F =24.0Hz),13.80. 19 F NMR (376 MHz, CDCl3) δ-164.4.

[0155] HRMS(ESI):calc.for[C 12 H 10 O3ClF+Na] + 233.0770; found 233.0776

[0156] Optical Rotation:[α] 25 D2.9(c=1,CHCl3).

Claims

1. A method for synthesizing a flexible chiral aryl iodide catalyst, characterized in that: The steps include: 1) The amino group of chloramphenicol represented by formula (1) is protected by di-tert-butyl dicarbonate and then recrystallized by solvent to obtain the intermediate represented by formula (2); 2) reacting the intermediate represented by formula (2) with chlorosilane in a solvent under the action of a base to generate an intermediate represented by formula (3); 3) reacting the intermediate represented by formula (3) with thionyl chloride in the presence of imidazole and a base to generate the intermediate represented by formula (4); 4) reacting the intermediate represented by formula (4) in a solvent under the action of an oxidant and a catalyst, and obtaining the intermediate represented by formula (5) by recrystallization; 5) reacting the intermediate represented by formula (5) and the 2-iodobenzene derivative represented by formula (6) in the presence of a base to generate the intermediate represented by formula (7); 6) removing the protecting group of the intermediate represented by formula (7) in a solvent under the action of an acid to generate the intermediate represented by formula (8); 7) reacting the intermediate represented by formula (8) with an acyl chloride, sulfonamide, isocyanate or isothiocyanate in the presence of a base, and recrystallizing the reaction product from a solvent to obtain a chiral aryl iodide catalyst represented by formula (9); 8) The intermediate represented by formula (9) is subjected to the action of tetrabutylammonium fluoride to remove the silicon group to obtain an intermediate, which is then further reacted with an acyl chloride, sulfonamide, isocyanate or isothiocyanate, and recrystallized from a solvent to obtain a chiral aryl iodide catalyst represented by formula (10). The reaction process is as follows: ， ， ， where R 1 is selected from hydroxyl protecting groups including trimethylsilyl, triethylsilyl, triethylpropylsilyl, diethylisopropylsilyl, dimethyl-tert-butylsilyl, tert-butyldimethylsilyl or tert-butyldiphenylsilyl; the substituent R 2 and R 12 Substituted or unsubstituted, when substituted R 2 and R 12 is selected from methyl, trifluoromethyl, methyl ester or ethyl ester; R 3 , R 4 , R 5 , R 6 Each is independently selected from an alkane, a phenyl group or a substituted phenyl group, the substituent on the substituted phenyl group is monosubstituted or polysubstituted, the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro, R 7 is selected from triphenylmethyl or mesityl, R 8 , R 9 , R 10 and R 11 Each is independently selected from an alkane, a phenyl group or a substituted phenyl group, the substituent on the substituted phenyl group is monosubstituted or polysubstituted, and the substituent is methyl, methoxy, trifluoromethyl, trifluoromethoxy, ethyl, isopropyl, tert-butyl, halogen or nitro; The amount of thionyl chloride used in step 3) is 1.0-5.0 equivalents of the intermediate shown in formula (3), the amount of imidazole used is 1.0-20.0 equivalents of the intermediate shown in formula (3), and the base is triethylamine or N,N- Diisopropylethylamine, the amount of the base used is 2.0-10.0 equivalents of the intermediate represented by formula (3), the reaction temperature is -70-0°C, and the reaction time is 2-5 h; Step 4) The oxidant is sodium periodate, and the amount of the oxidant is 1.0-5.0 equivalents of the intermediate represented by formula (4). The catalyst is hydrated ruthenium trichloride, and the amount of the catalyst is 1-30 mol% of the intermediate represented by formula (4). The solvent is acetonitrile and water or dichloromethane and water, and the amount of the solvent is 1:

1. The reaction temperature is 0-30°C, and the reaction time is 2-6 h. In step 5), the amount of the intermediate represented by formula (5) used is 2.0-10.0 equivalents of the 2-iodobenzene derivative represented by formula (6), the base is sodium hydride, and the amount of the base used is 2.0-10.0 equivalents of the 2-iodobenzene derivative represented by formula (6). The reaction temperature is -20-0°C and the reaction time is 2-6 h.

2. The synthesis method according to claim 1, wherein In step 1), the amount of di-tert-butyl dicarbonate used is 1.0-10.0 equivalents of the compound represented by formula (1). The solvent used for recrystallization of the intermediate (2) is ethyl acetate, methanol or diethyl ether. The reaction temperature is -20-0°C and the reaction time is 2-7 h.

3. The synthesis method according to claim 1, wherein Step 2) The chlorosilane is tert-butyldiphenylchlorosilane, tert-butyldimethylchlorosilane, trimethylchlorosilane, triethylchlorosilane, triisopropylchlorosilane, dimethylisopropylchlorosilane or diethylisopropylchlorosilane, and the amount of the chlorosilane is 1.0-5.0 equivalents of the intermediate shown in formula (2). The solvent is dichloromethane, dichloroethane, chloroform, tetrahydrofuran or N,N -dimethylformamide, the reaction temperature is -20-0°C, and the reaction time is 2-5 h.

4. The synthesis method according to claim 1, wherein Step 6) The solvent is dichloromethane, dichloroethane or chloroform, the acid is trifluoroacetic acid, hydrochloric acid or sulfuric acid, the amount of acid to solvent is 1:3-1:10, the reaction temperature is -20-0°C, and the reaction time is 1-5 h.

5. The synthesis method according to claim 1, wherein In step 7), the amount of the acid chloride, sulfonamide, isocyanate or isothiocyanate used is 2.0-10.0 equivalents of the intermediate represented by formula (8), the base is triethylamine, and the amount of the base used is 2.0-10.0 equivalents of the intermediate represented by formula (8), the recrystallization solvent is tetrahydrofuran, methyl tert-butyl ether or dioxane, the reaction temperature is -20-50°C, and the reaction time is 1-8 h; in step 8), the amount of tetrabutylammonium fluoride used is 1.0-20.0 equivalents of the compound represented by formula (9), the amount of the acid chloride, sulfonamide, isocyanate or isothiocyanate used is 2.0-10.0 equivalents of the intermediate represented by formula (9), the base is triethylamine, and the amount of the base used is 2.0-10.0 equivalents of the compound represented by formula (9).

6. Use of a flexible chiral aryl iodide catalyst synthesized by the synthesis method according to claim 1 with chloramphenicol as a chiral source, characterized in that: Chiral aryl iodide catalysts can enantioselectively synthesize γ-butyrolactone, chroman ring, isochroman ring, oxazolidinone, piperidine, pyrrolidine, and aziridine through intramolecular oxidative lactonization, etherification, amidation, and arylation reactions.

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