1,3-dithiane-substituted cyclobutene derivatives, processes for their preparation and use

Abstract

The application belongs to the field of organic chemistry and provides a 1,3-dithiane substituted cyclobutene derivative and a preparation method and application thereof. That is, with acetylenic thiane compound and cinnamate compound as raw materials, intermolecular cycloaddition occurs under the promotion of a base to obtain. And through negative ion relay chemistry, a more complex cyclobutene can be obtained. The structural feature is that it has a structure shown in formula (I), wherein R 1 , R 2 is aryl; R 3 is alkyl or aryl; X = oxygen (O) or sulfur (S); and E is hydrogen, alkyl or aryl. The method provided by the application uses a cheap strong base as a promoter, avoids using a noble metal catalyst, has mild reaction conditions, simple operation, wide substrate applicability, does not need anhydrous and oxygen-free operation, has strong practicability and a prospect of industrial application. The method provided by the application can be used for synthesis and later modification of natural products, drug molecules and functional material molecules.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthetic chemistry, and particularly relates to a 1,3-dithiane-substituted cyclobutene derivative, a preparation method and application thereof. BACKGROUND

[0002] Cyclobutene skeleton is widely present in natural products and bioactive molecules (Liebigs Ann. Chem. 1989, 11, 1075-1079. Tetrahedron Lett. 1992, 33, 353-356. Tetrahedron Lett. 2001, 42, 5323-5325.), and the unique ring strain and double bond characteristics of the skeleton endow it with rich functionalization, thus making it an important synthetic building block (Acc. Chem. Res. 2016, 49, 2444-2458. J. Am. Chem. Soc. 2024, 146, 12691-12701.).

[0003] Therefore, the skeleton shows important application value in many fields such as medicine, biology and materials. However, so far, the synthesis of the skeleton is mainly achieved by transition metal catalysis and photocatalysis (Curr. Org. Synth. 2009, 6, 219-238. Chem. Rec. 2021, 21, 1144-1160. Chem. Rev. 2021, 121, 8613-8684.). However, such methods have obvious limitations, such as the use of expensive noble metal catalysts ruthenium, rhodium, palladium and gold; the reaction needs to be carried out in anhydrous and anaerobic atmosphere; and an excess of oxidizing agent is required. Therefore, it is very valuable to develop a non-noble metal catalytic, mild condition and simple operation method for synthesizing cyclobutene compounds.

[0004] 1,3-dithiane, as an aldehyde ketone protecting group and a polarity conversion reagent, plays an important role in organic synthesis and total synthesis of natural products (J. Am. Chem. Soc. 2019, 141, 8088-8092. Sci. Adv. 2024, 10, eadp9375. J. Am. Chem. Soc. 2023, 145, 18240-18246.). 1,3-dithiane-substituted drug molecules can consume ROS (reactive oxygen species) in vivo, reduce oxidative stress (ACS Nano. 2022, 16, 21225-21239). At the same time, the introduced sulfur atom can change the liposolubility, metabolic stability and bioavailability of the drug molecule, thereby optimizing the pharmacokinetic properties of the drug. SUMMARY

[0005] The application aims to provide a 1,3-dithiane-substituted cyclobutene derivative and a preparation method and application thereof, i.e. 2-ethynyl-1,3-dithiane derivative, cinnamate compound, suitable solvent, strong base and electrophilic reagent are sequentially added in a reactor, and a cyclobutene compound is obtained by reaction at a suitable temperature. The method does not need noble metal catalysis, does not need anhydrous and anaerobic operation, has mild conditions, wide substrate applicability, high stereoselectivity and high yield.

[0006] The application relates to a 1,3-dithiane-substituted cyclobutene derivative.

[0007]

[0008] R is a substituted phenyl (the substituents are selected from one or more of hydrogen, methyl, methoxy, fluorine, chlorine and trifluoromethoxy) or naphthyl; R 1 is a substituted phenyl (the substituents are selected from one or more of hydrogen, methyl, methoxy, fluorine, chlorine, bromine and trifluoromethoxy), furanyl, thienyl or pyridyl; R 2 is a substituted phenyl (the substituents are selected from one or more of hydrogen, methyl, methoxy, fluorine, chlorine, bromine and trifluoromethoxy), furanyl, thienyl or pyridyl; R 3 is methyl, ethyl, n-butyl, cyclohexyl, benzyl, cyclododecyl, furan derivative, adamantane derivative, L-geraniol derivative or R-(-)-nopol derivative;

[0009] E is hydrogen, n-nonyl, cyclopentyl, 2-(2,3-dihydrobenzofuran-5-yl)ethyl, oxetan-3-yl, benzyl, 2-methylallyl, but-2-yn-1-yl, 2-(phenylsulfonyl)ethyl, 4-methoxybenzoyl, 2-chloropyrid-4-yl, 2-methylpyrimidin-4-yl or 4-nitrophenyl;

[0010] X is oxygen (O) or sulfur (S).

[0011] The application relates to a preparation method of a 1,3-dithiane-substituted cyclobutene derivative.

[0012]

[0013] In the technical scheme, the organic solvent is one of dimethyl sulfoxide (DMSO), tetrahydrofuran (THF) and N,N-dimethylformamide (DMF).

[0014] The strong base is one of potassium tert-butoxide, sodium tert-butoxide, potassium ethoxide, sodium ethoxide, potassium methoxide and sodium methoxide.

[0015] In the technical solution, the electrophilic reagent is water, alkyl halide, aryl halide, acyl halide, Michael acceptor, etc.

[0016] In the technical solution, the molar ratio of the strong base, 2-ethynyl-1,3-dithiane derivative (II), cinnamate compound (III) and electrophilic reagent is (0.1-1.2):1:(1-3):(1-3).

[0017] In the technical solution, the reaction steps include: adding 2-ethynyl-1,3-dithiane derivative, cinnamate compound, suitable solvent and strong base into a reaction bottle in sequence, stirring at 50°C for 1-10 minutes, then adding electrophilic reagent and continuing to stir, monitoring the reaction by thin layer chromatography, adding saturated brine into the reaction system to quench the reaction after the raw material is completely consumed, extracting with ethyl acetate (15 ml) for three times, washing the combined organic phase with saturated brine (40 ml) for three times, drying with anhydrous sodium sulfate, filtering, removing volatile matter under vacuum, and column chromatography to obtain the product. DETAILED DESCRIPTION

[0018] The following examples can make the professional technical personnel more fully understand the present application, but do not limit the present application in any way. The raw materials used in the present application are known compounds, which can be purchased from the market or synthesized by known methods in the art.

[0019] Example 1: Preparation of compound trans-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate:

[0020] In a 25 ml round-bottom flask, 2-(phenylacetylene)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (105 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, then potassium phosphate (13 mg, 0.06 mmol) and sodium tert-butoxide (6 mg, 0.06 mmol) were added, stirring at 50°C for 10 min, monitoring the reaction by thin layer chromatography, adding saturated brine into the reaction system to quench the reaction after the reaction was completed, extracting with ethyl acetate (15 ml) for three times, washing the combined organic phase with saturated brine (30 ml) for three times, drying with anhydrous sodium sulfate, filtering, removing volatile matter under vacuum, and column chromatography to obtain the product, with a yield of 72%.

[0021] The structure and nuclear magnetic resonance data of the product obtained in Example 1, trans-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate, are as follows:

[0022]

[0023] trans-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ethyl ester 1 H NMR (400 MHz, Chloroform-d) δ 7.48 - 7.43 (m, 2H), 7.27 (d, J = 8.1 Hz, 4H), 7.25 (t, J = 2.2 Hz, 4H), 5.38 (s, 1H), 4.30 - 4.18 (m, 3H), 3.49 (d, J = 1.8 Hz, 1H), 3.11 - 2.93 (m, 2H), 2.91 - 2.80 (m, 2H), 2.21 - 2.06 (m, 1H), 2.04 - 1.88 (m, 1H), 1.32 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 172.2, 146.2, 140.1, 134.9, 132.7, 128.8, 128.5, 128.4, 128.2, 127.3, 127.3, 61.0, 53.4, 48.7, 45.3, 31.0, 25.3, 14.4.

[0024] Example 2: Preparation of compound trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(o- tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0025] In a 25 ml round bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), corresponding cinnamate compound (105 mg, 0.6 mmol) and 6 ml of DMF were added in sequence, followed by the addition of potassium phosphate (13 mg, 0.06 mmol) and sodium tert-butoxide (30 mg, 0.6 mmol) and stirring at 50 °C for 10 min, monitoring the reaction by thin layer chromatography, after the reaction was completed, saturated brine was added to quench the reaction in the reaction system, and extracted with ethyl acetate (15 ml) three times, the organic phase was combined, washed with saturated brine (30 ml) three times, dried over anhydrous sodium sulfate, filtered, and the volatile matter was removed under vacuum, and column chromatography gave the product with a yield of 68%.

[0026] The structure and NMR data of the product obtained in Example 2, trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0027]

[0028] Trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1 HNMR (400 MHz, Chloroform-d) δ 7.49 - 7.44 (m, 2H), 7.36 - 7.30 (m, 2H), 7.30 - 7.27 (m, 1H), 7.18 (dd, J = 7.7, 1.3 Hz, 1H), 7.15 - 7.10 (m, 1H), 7.07 - 7.02 (m, 2H), 5.41 (s, 1H), 4.52 (d, J = 1.9 Hz, 1H), 3.80 (s, 3H), 3.41 (d, J = 0.9 Hz, 1H), 3.10 - 2.95 (m, 2H), 2.93 - 2.84 (m, 2H), 2.38 (s, 3H), 2.17 - 2.09 (m, 1H), 2.02 - 1.89 (m, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 173.1, 145.9, 138.1, 136.3, 134.6, 132.7, 130.4, 128.6, 128.5, 128.2, 127.0, 126.4, 126.3, 52.7, 52.2, 45.2, 44.9, 30.9, 25.1, 19.6.

[0029] Preparation of the product trans-2-(1,3-dithian-2-yl)-4-(2-methoxyphenyl)-3- phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 3:

[0030] In a 25 ml round bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (115 mg, 0.6 mmol) and 6 ml of DMF were sequentially added, followed by the addition of potassium phosphate (13 mg, 0.06 mmol) and potassium ethoxide (5 mg, 0.06 mmol). The reaction was stirred at 50 °C for 10 min, monitored by thin layer chromatography and, after completion of the reaction, the reaction mixture was quenched with saturated brine and extracted with ethyl acetate (15 ml) three times. The organic phases were combined, washed with saturated brine three times, dried over anhydrous sodium sulfate, filtered and, after removing the volatile substances under vacuum, the product was obtained by column chromatography with a yield of 69%.

[0031] The structure and NMR data of the product trans-2-(1,3-dithian-2-yl)-4-(2- methoxyphenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 3 are as follows:

[0032]

[0033] Methyl trans-2-(1,3-dithiadin-2-yl)-4-(2-methoxyphenyl)-3-phenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.50–7.46(m,2H),7.35–7.27(m,3H),7.18(td,J=7.8,1 .7Hz,1H),6.99(dd,J=7.5,1.7Hz,1H),6.85(dd,J=8.2,1.1Hz,1H),6.78(td,J=7.5,1 .1Hz,1H),5.38(s,1H),4.64(d,J=1.8Hz,1H),3.82(s,3H),3.79(s,3H),3.44(t,J=1. 3Hz,1H),3.08–2.93(m,2H),2.90–2.83(m,2H),2.15–2.06(m,1H),1.99–1.89(m,1H). 13 CNMR(101MHz,Chloroform-d)δ173.3,157.7,145.9,134.5,133.1,128.5,128.4,128. 3,128.1,128.1,127.6,120.6,110.4,55.5,52.3,52.1,45.2,42.6,30.9,30.8,25.1.

[0034] Preparation of methyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylate, the product obtained in Example 4:

[0035] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (105 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 62%.

[0036] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-4-(2-methoxyphenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 4 are as follows:

[0037]

[0038] Methyl trans-2-(1,3-dithiadin-2-yl)-4-(2-methoxyphenyl)-3-phenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.46–7.41(m,2H),7.32–7.27(m,2H),7.26–7.21(m,1H),7.15(d,J=8.1Hz,2H),7.08(d,J=7.9Hz,2H),5.40(s,1H),4 .23(d,J=1.7Hz,1H),3.77(s,3H),3.49(d,J=1.7Hz,1H),3.09–2.97(m,2 H),2.93–2.84(m,2H),2.30(s,3H),2.18–2.10(m,1H),2.03–1.91(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.8,146.4,136.9,136.9,134.7,132.7,129. 5,128.5,128.4,128.2,127.2,53.2,52.2,48.4,45.2,31.0,31.0,25.2,21.3.

[0039] Preparation of methyl trans-2-(1,3-dithiadin-2-yl)-4-(4-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 5:

[0040] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (108 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and sodium ethoxide (5 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 62%.

[0041] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-4-(4-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 5 are as follows:

[0042]

[0043] Methyl trans-2-(1,3-dithiadin-2-yl)-4-(4-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylate 1 HNMR(400MHz,Chloroform-d)δ7.45–7.39(m,2H),7.32–7.29(m,1H),7.29–7.27(m,1H),7.26–7.24(m,1H),7.24–7.18(m,2H),7.02–6.92(m,2H),5 .39(s,1H),4.25(d,J=1.7Hz,1H),3.78(s,3H),3.46(d,J=1.8Hz,1H),3. 12–2.95(m,2H),2.93–2.83(m,2H),2.20–2.08(m,1H),2.03–1.90(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.5,162.1(d,J=245.3Hz),146.2,135.6(d,J=3.2Hz),134.9,132.4,1 28.8(d,J=8.3Hz),128.7,128.5,128.1,115.7(d,J=21.4Hz),53.2,52.3,47.8,45.1,31.0,30.9,25.1.

[0044] Preparation of methyl trans-4-(4-chlorophenyl)-2-(1,3-dithiadin-2-yl)-3-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 6:

[0045] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (117 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 58%.

[0046] The structure and NMR data of the product trans-4-(4-chlorophenyl)-2-(1,3-dithiadin-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 6 are as follows:

[0047]

[0048] Methyl trans-4-(4-chlorophenyl)-2-(1,3-dithiadin-2-yl)-3-phenylcyclobut-2-ene-1-carboxylate 1 HNMR(400MHz,Chloroform-d)δ7.43–7.38(m,2H),7.33–7.26(m,3H),7.24(d,J=2.2Hz,2H),7.21–7.16(m,2H),5.39(s,1H),4.24 (d,J=1.7Hz,1H),3.78(s,3H),3.46(d,J=1.7Hz,1H),3.10–2.97(m,2H),2.92–2.84(m,2H),2.18–2.11(m,1H),2.02–1.90(m,1H). 13 C NMR (101MHz, Chloroform-d) δ172.5,146.0,138.5,135.0,133.0,132.3,129.1,128.8,128.6,128.5,128.1,53.0,52.3,47.9,45.1,31.0,30.9,25.1.

[0049] Preparation of the product trans-4-(4-bromophenyl)-2-(1,3-dithiadin-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 7:

[0050] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (143 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and sodium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 59%.

[0051] The structure and NMR data of the product trans-4-(4-bromophenyl)-2-(1,3-dithiadin-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 7 are as follows:

[0052]

[0053] Methyl trans-4-(4-bromophenyl)-2-(1,3-dithiadin-2-yl)-3-phenylcyclobut-2-ene-1-carboxylate 1HNMR(400MHz,Chloroform-d)δ7.44–7.37(m,4H),7.34–7.27(m,3H),7.16–7.10(m,2H),5.39(s,1H),4.23(d,J=1.7Hz ,1H),3.78(s,3H),3.46(d,J=1.7Hz,1H),3.09–2.97(m,2H),2.93–2.84(m,2H),2.17–2.10(m,1H),2.01–1.91(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.4,145.9,139.0,135.0,132.3,132.0,129.0,128.8,128.5,128.1,121.1,52.9,52.3,47.9,45.1,31.0,30.9,25.1.

[0054] Preparation of ethyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(4-(trifluoromethyl)phenyl)cyclobut-2-ene-1-carboxylate, the product obtained in Example 8:

[0055] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (146 mg, 0.6 mmol), and 6 mL of THF were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 58%.

[0056] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(4-(trifluoromethyl)phenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester obtained in Example 8 are as follows:

[0057]

[0058] Ethyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(4-(trifluoromethyl)phenyl)cyclobut-2-ene-1-carboxylate 1H NMR(400MHz,Chloroform-d)δ7.54(d,J=8.0Hz,2H),7.46–7.40(m,2H),7.37(d,J=8.0Hz,2H),7.34–7.26(m,3H),5.38(s,1H),4.34–4.31(m,1H) ),4.30–4.21(m,2H),3.46(d,J=1.7Hz,1H),3.11–2.95(m,2H),2.94–2. 84(m,2H),2.19–2.10(m,1H),2.06–1.89(m,1H),1.33(t,J=7.1Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ171.7,145.6,144.3,135.4,132.2,129.6(q,J=32.3Hz),128.8,128.6 ,128.2,127.6,125.9(q,J=3.7Hz),124.3(q,J=271.9Hz),61.3,53.1,48.0,45.1,31.0,25.2,14.4.

[0059] Preparation of methyl trans-2-(1,3-dithiadin-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 9:

[0060] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (108 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 78%.

[0061] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 9 are as follows:

[0062]

[0063] Methyl trans-2-(1,3-dithiadin-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylate 1HNMR(400MHz,Chloroform-d)δ7.45–7.38(m,2H),7.35–7.26(m,3H),7.24–7.19(m,1H),7.04(dt,J=7.7,1.3Hz,1H),6.98–6.86(m,2H),5.3 9(s,1H),4.27–4.25(m,1H),3.78(s,3H),3.49(t,J=1.2Hz,1H),3.10– 2.95(m,2H),2.91–2.82(m,2H),2.17–2.07(m,1H),2.01–1.88(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.4,163.2(d,J=246.4Hz),145.8,142.6(d,J=7.1Hz),135.1,132.3,130.4(d,J=8.3Hz),128.7,12 8.5, 128.1, 123.0 (d, J = 2.8Hz), 114.3 (d, J = 21.3Hz), 114.1 (d, J = 21.4Hz), 52.9, 52.3, 48.1 (d, J = 1.8Hz), 45.0, 30.93, 30.91, 25.1.

[0064] Preparation of ethyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylate, the product obtained in Example 10:

[0065] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (160 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 53%.

[0066] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester obtained in Example 10 are as follows:

[0067]

[0068] Ethyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.47–7.43(m,1H),7.34–7.27(m,1H),5.39(s,0H),4.25(qd,J=7.2,1.7Hz,1H),4.16(d,J=1.7Hz,0H),3.81(s ,1H),3.78(s,3H),3.48(t,J=1.1Hz,0H),3.09–2.94(m,1H),2.94–2.8 3(m,1H),2.19–2.09(m,1H),2.02–1.89(m,1H),1.33(t,J=7.1Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ172.2,153.5,146.3,137.1,135.9,135.1,132.7,128 .6,128.5,128.2,104.0,61.1,60.9,56.2,53.5,48.9,45.2,31.0,31.0,25.2,14.4.

[0069] Preparation of trans-benzyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester obtained in Example 11:

[0070] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (143 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 56%.

[0071] The structure and NMR data of the product trans-benzyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester obtained in Example 11 are as follows:

[0072]

[0073] trans-benzyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester 1 H NMR(400MHz,Chloroform-d)δ7.44(ddd,J=7.9,4.9,1.6Hz,4H),7.39–7.26(m,6H),7.25–7.18(m,5H),5.35(s,1H),5.23(q,J=12. 4Hz,2H),4.27(d,J=1.7Hz,1H),3.55(d,J=1.7Hz,1H),3.06–2.91(m,2H),2.90–2.78(m,2H),2.15–2.07(m,1H),2.02–1.86(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.1,146.4,140.0,136.2,134.8,132.6,128.9,12 8.6,128.5,128.4,128.3,128.2,127.3,66.8,53.3,48.6,45.1,31.0,31.0,25.2.

[0074] Preparation of trans-cyclohexyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester obtained in Example 12:

[0075] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (138 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 53%.

[0076] The structure and NMR data of the product trans-cyclohexyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester obtained in Example 12 are as follows:

[0077]

[0078] trans-cyclohexyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester. 1HNMR(400MHz,Chloroform-d)δ7.52–7.40(m,2H),7.32–7.27(m,3H),7.26–7.19 (m,5H),5.36(s,1H),5.29(s,1H),4.89(tt,J=8.8,3.9Hz,1H),4.24(d,J=1.7Hz, 1H),3.46(d,J=1.7Hz,1H),3.08–2.96(m,2H),2.94–2.84(m,2H),2.17–2.08(m, 1H),2.03–1.83(m,4H),1.80–1.69(m,2H),1.54–1.45(m,2H),1.44–1.25(m,3H). 13 C NMR(101MHz,Chloroform-d)δ171.5,146.2,140.3,135.1,132.7,128.8,128.4,128.4,128 .3,127.3,127.2,73.2,53.8,48.7,45.4,31.7,31.7,31.2,31.1,25.6,25.3,23.88,23.85.

[0079] Preparation of ethyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-en-1-carboxylate, the product obtained in Example 13:

[0080] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (160 mg, 0.9 mmol), and 8 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 53%.

[0081] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-en-1-carboxylic acid ethyl ester obtained in Example 13 are as follows:

[0082]

[0083] Ethyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-ene-1-carboxylate1 HNMR(400MHz,Chloroform-d)δ8.54–8.48(m,2H),7.44–7.40(m,2H),7.34–7.27(m,3H),7.21–7.15(m,2H),5.37(s,1H),4.31–4.2 0(m,3H),3.47(d,J=1.7Hz,1H),3.11–2.95(m,2H),2.94–2.84(m,2H),2.25–2.10(m,1H),2.07–1.92(m,1H),1.33(t,J=7.1Hz,3H). 13 CNMR(101MHz,Chloroform-d)δ171.5,150.4,149.2,145.2,135.6,132.0,128.9,128.6,128.1,122.5,61.4,52.5,47.3,45.0,31.0,25.2,14.4.

[0084] Preparation of ethyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-en-1-carboxylate, the product obtained in Example 14:

[0085] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (92 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 58%.

[0086] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-en-1-carboxylic acid ethyl ester obtained in Example 14 are as follows:

[0087]

[0088] Methyl trans-2-(1,3-dithiadin-2-yl)-4-(furan-2-yl)-3-phenylcyclobut-2-ene-1-carboxylate 1HNMR(400MHz,Chloroform-d)δ7.50–7.42(m,2H),7.36–7.27(m,4H),6.28(dd,J=3.2,1.9Hz,1H),6.11(d,J=3.2Hz,1H),5.34(s,1H), 4.36(d,J=1.8Hz,1H),3.79(s,3H),3.75(d,J=1.9Hz,1H),3.06–2.95(m,2H),2.91–2.82(m,2H),2.17–2.08(m,1H),2.01–1.88(m,1H). 13 C NMR (101MHz, Chloroform-d) δ172.4,153.0,144.7,142.1,135.2,132.6,128.7,128.5,127.9,110.5,107.1,52.3,50.4,45.0,41.7,30.9,30.8,25.2.

[0089] Preparation of methyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(thiophen-3-yl)cyclobut-2-ene-1-carboxylate, the product obtained in Example 15:

[0090] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (92 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 57%.

[0091] The structure and NMR data of the product trans-2-(1,3-dithiapan-2-yl)-3-phenyl-4-(thiophen-3-yl)cyclobut-2-en-1-carboxylic acid methyl ester obtained in Example 15 are as follows:

[0092]

[0093] Methyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(thiophen-3-yl)cyclobut-2-ene-1-carboxylate 1HNMR(400MHz,Chloroform-d)δ7.48–7.43(m,2H),7.34–7.26(m,3H),7.23(dd,J=5.0,2.9Hz,1H),7.06(dd,J=3.0,1.3Hz,1H),6.98(dd,J=5.0,1.3Hz ,1H),5.37(s,1H),4.37(d,J=1.8Hz,1H),3.78(s,3H),3.58–3.51(m,1H),3 .10–2.94(m,2H),2.93–2.82(m,2H),2.19–2.09(m,1H),2.02–1.88(m,1H). 13 C NMR (101MHz, Chloroform-d) δ172.7,146.6,141.0,134.5,132.7,128.6,128.5,128.1,126.4,126.3,121.7,52.6,52.3,45.1,44.0,30.9,25.2.

[0094] Preparation of methyl trans-4-(benzodioxacyclopenten-5-yl)-2-(1,3-dithiadin-2-yl)-3-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 16:

[0095] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (120 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 68%.

[0096] The structure and NMR data of the product trans-4-(benzodioxacyclopenten-5-yl)-2-(1,3-dithiadin-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 16 are as follows:

[0097]

[0098] Methyl trans-4-(benzodioxacyclopenten-5-yl)-2-(1,3-dithiadin-2-yl)-3-phenylcyclobut-2-ene-1-carboxylate 1H NMR(400MHz,Chloroform-d)δ7.50–7.38(m,2H),7.34–7.25(m,4H),7.27–7.20(m,2H),6.77–6.68(m,3H),5.92–5.89(m,2H),5.38(s,1H ),4.18(d,J=1.8Hz,1H),3.77(s,3H),3.46(d,J=1.8Hz,1H),3.11–2.94(m,2H),2.93–2.81(m,2H),2.20–2.07(m,1H),2.07–1.88(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.7,148.1,146.9,146.3,134.8,133.8,132.5,128.6 ,128.5,128.2,120.8,108.5,107.2,101.1,53.3,52.2,48.5,45.1,31.0,30.9,25.2.

[0099] Preparation of trans-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate butyl ester obtained in Example 17:

[0100] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (120 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 73%.

[0101] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate obtained in Example 17 are as follows:

[0102]

[0103] trans-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate 1H NMR(400MHz,Chloroform-d)δ7.47–7.43(m,2H),7.31–7.27(m,3H),7.26–7.19(m,5H),5.37(s,1H),4.25(d,J=1.7Hz,1H),4.24–4.13(m,2H),3.49( d,J=1.7Hz,1H),3.08–2.95(m,2H),2.93–2.84(m,2H),2.19–2.08(m,1H), 2.02–1.89(m,1H),1.67(m,2H),1.49–1.37(m,2H),0.94(t,J=7.4Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ172.3,146.2,140.1,134.9,132.7,128.9,128.5,128 .4,128.3,127.3,127.3,65.0,53.4,48.7,45.3,31.1,31.0,30.8,25.3,19.4,13.9.

[0104] Preparation of trans-furan-3-ylmethyl-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester, the product obtained in Example 18:

[0105] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (138 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (30 mg, 0.6 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 52%.

[0106] The structure and NMR data of the product trans-furan-3-ylmethyl-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester obtained in Example 18 are as follows:

[0107]

[0108] trans-furan-3-ylmethyl-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester 1HNMR(400MHz,Chloroform-d)δ7.52(s,1H),7.47–7.41(m,2H),7.40(d,J=1.8Hz,1H),7.31–7.25(m,5H),7.22(d,J=7.0Hz,3H),6.49(d,J=1.8Hz,1H),5 .35(s,1H),5.15–5.03(m,2H),4.24(d,J=1.7Hz,1H),3.51(d,J=1.7Hz,1H), 3.06–2.93(m,2H),2.91–2.79(m,2H),2.18–2.07(m,1H),2.01–1.86(m,1H). 13 CNMR(101MHz,Chloroform-d)δ172.1,146.4,143.3,141.8,139.9,134.7,132.6,128.9,1 28.6,128.4,128.3,127.3,127.3,120.6,110.9,58.4,53.2,48.6,45.2,31.0,31.0,25.2.

[0109] Preparation of trans-S-ethyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-thiocarbamate, the product obtained in Example 19:

[0110] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (115 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 62%.

[0111] The structure and NMR data of the product trans-S-ethyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-thiocarbamate obtained in Example 19 are as follows:

[0112]

[0113] trans-S-ethyl-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-thiocarbamate 1HNMR(400MHz,Chloroform-d)δ7.49–7.44(m,2H),7.32–7.26(m,5H),7.26–7.21(m,2H),5.36(s,1H),4.22(d,J=1.7H z,1H),3.69(t,J=1.2Hz,1H),3.09–2.96(m,4H),2.89(m,2H),2.14(m,1H),2.03–1.92(m,1H),1.30(t,J=7.4Hz,3H). 13 C NMR (101MHz, Chloroform-d) δ198.2,146.3,139.9,135.2,132.4,128.9,128.7,128.4,127.4,127.3,61.5,50.1,45.5,31.2,31.2,25.2,23.7,14.7.

[0114] Preparation of trans-(R)-3,7-dimethyloct-6-en-1-yl-2-(1,3-dithiapan-2-yl)-3,4-diphenylcyclobut-2-en-1-carboxylic acid ester obtained in Example 20:

[0115] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (172 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 55%.

[0116] The structure and NMR data of the product trans-(R)-3,7-dimethyloct-6-en-1-yl-2-(1,3-dithiapan-2-yl)-3,4-diphenylcyclobut-2-en-1-carboxylic acid ester obtained in Example 20 are as follows:

[0117]

[0118] trans-(R)-3,7-dimethyloct-6-en-1-yl-2-(1,3-dithiapan-2-yl)-3,4-diphenylcyclobut-2-en-1-carboxylic acid ester 1H NMR(400MHz,Chloroform-d)δ7.5–7.4(m,2H),7.3–7.3(m,3H),7.3–7.2(m,5H),5.4 (s,1H),5.1(tt,J=5.5,2.9Hz,1H),4.3–4.1(m,3H),3.5(d,J=1.7Hz,1H),3.1–2.9(m ,2H),2.9–2.8(m,2H),2.2–2.1(m,1H),2.1–1.9(m,3H),1.8–1.7(m,1H),1.7(s,3H) ,1.6(s,4H),1.6–1.4(m,1H),1.4–1.3(m,1H),1.3–1.1(m,2H),0.9(d,J=6.6Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ172.3,146.2,140.1,134.9,132.6,131.4,128.8,128.5,128.4,128.2,1 27.3,127.3,124.8,63.7,53.4,48.6,45.3,37.2,35.6,31.0,29.7,29.7,25.8,25.6,25.2,19.5,17.8.

[0119] Preparation of trans-(adamantane-1-yl)methyl-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester, the product obtained in Example 21:

[0120] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (178 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 55%.

[0121] The structure and NMR data of the product trans-(adamantane-1-yl)methyl-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-en-1-carboxylic acid ester obtained in Example 21 are as follows:

[0122]

[0123] trans-(adamantane-1-yl)methyl-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester 1 H NMR(400MHz,Chloroform-d)δ7.52–7.44(m,2H),7.32–7.27(m,4H),7.26–7.20(m,3H),5.35(s,1H),4.29(d,J=1.7Hz,1H),3.85–3.69(m,2H) ,3.51(d,J=1.8Hz,1H),3.06–2.94(m,2H),2.93–2.83(m,2H),2.17–2. 08(m,1H),2.03–1.89(m,4H),1.79–1.61(m,7H),1.60(d,J=2.8Hz,5H). 13 C NMR(101MHz,Chloroform-d)δ172.3,146.3,140.2,134.9,132.6,128.8,128.5,128.4, 128.4,127.3,127.2,74.7,53.5,48.7,45.3,39.5,37.1,33.5,31.2,31.1,28.2,25.2.

[0124] Preparation of trans-2-((1R,5S)-6,6-dimethyldicyclohepta-2-en-2-yl)ethyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-en-1-carboxylic acid ester obtained in Example 22:

[0125] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (178 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 68%.

[0126] The structure and NMR data of the product trans-2-((1R,5S)-6,6-dimethyldicyclohepta-2-en-2-yl)ethyl-2-(1,3-dithiapan-2-yl)-3,4-diphenylcyclobut-2-en-1-carboxylic acid ester obtained in Example 22 are as follows:

[0127]

[0128] trans-2-((1R,5S)-6,6-dimethyldicyclohepta-2-en-2-yl)ethyl-2-(1,3-dithiapan-2-yl)-3,4-diphenylcyclobut-2-en-1-carboxylic acid ester 1 H NMR(400MHz,Chloroform-d)δ7.47–7.42(m,2H),7.31–7.26(m,3H),7.26–7.19(m,5H),5.37(s,1H) ),5.32(dp,J=3.1,1.5Hz,1H),4.24(d,J=1.7Hz,1H),4.23–4.12(m,2H),3.47(d,J=1.7Hz,1H),3.0 8–2.96(m,2H),2.92–2.81(m,2H),2.40–2.29(m,3H),2.29–2.17(m,2H),2.16–2.10(m,1H),2.09–2 .04(m,2H),2.04–1.91(m,1H),1.24(d,J=4.5Hz,3H),1.15(d,J=8.5Hz,1H),0.81(d,J=2.0Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ172.2,146.2,144.4,140.1,134.9,132.7,128.8,128.5,128.4,128.3,127.3 ,127.3,118.9,63.3,53.4,48.7,45.8,45.2,40.9,38.2,36.1,31.82,31.79,31.5,31.0,26.4,25.3,21.3.

[0129] Preparation of trans-cyclododecyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester obtained in Example 23:

[0130] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamic ester compound (178 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 68%.

[0131] The structure and NMR data of the product trans-cyclododecyl-2-(1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester obtained in Example 23 are as follows:

[0132]

[0133] trans-cyclododecyl-2-(1,3-dithiadin-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ester 1 HNMR(400MHz,Chloroform-d)δ7.51–7.45(m,2H),7.31–7.26(m,3H),7.26–7.19( m,5H),5.34(s,1H),5.12(tt,J=7.2,4.7Hz,1H),4.24(d,J=1.8Hz,1H),3.45(d,J= 1.7Hz,1H),3.07–2.95(m,2H),2.93–2.82(m,2H),2.13(dtt,J=14.4,4.9,2.6Hz, 1H),2.05–1.89(m,1H),1.83–1.67(m,2H),1.66–1.54(m,3H),1.53–1.28(m,18H). 13 C NMR(101MHz,Chloroform-d)δ171.8,146.2,140.3,135.0,132.7,128.8,128.4,128.4,128.3,127.3,127 .2,73.1,53.7,48.7,45.3,31.2,31.1,29.3,29.1,25.3,24.3,24.0,23.6,23.5,23.4,23.3,21.2,21.1.

[0134] Preparation of methyl trans-2-(1,3-dithiadin-2-yl)-3-(2-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 24:

[0135] In a 25 mL round-bottom flask, 2-((2-methoxyphenyl)ethynyl)-1,3-dithiane (75 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 42%.

[0136] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3-(2-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 24 are as follows:

[0137]

[0138] Methyl trans-2-(1,3-dithiadin-2-yl)-3-(2-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.36(dd,J=7.6,1.8Hz,1H),7.25–7.18(m,5H),7 .16(td,J=6.2,2.4Hz,1H),6.86(td,J=7.5,1.0Hz,1H),6.80(d,J=8.3Hz,1H),5 .45(s,1H),4.39(d,J=1.8Hz,1H),3.78(s,3H),3.76(s,3H),3.52(d,J=1.8Hz,1 H),3.07–2.97(m,1H),2.93–2.82(m,3H),2.13–2.05(m,1H),1.98–1.87(m,1H). 13 C NMR(101MHz,Chloroform-d)δ173.2,157.5,144.5,140.7,135.7,130.3,130.0,128. 6,127.2,126.9,122.0,120.5,111.1,55.3,52.9,52.1,50.4,45.9,30.9,30.8,25.2.

[0139] Preparation of methyl trans-2-(1,3-dithiadin-2-yl)-3-(3-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 25:

[0140] In a 25 mL round-bottom flask, 2-((3-methoxyphenyl)ethynyl)-1,3-dithiane (75 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 57%.

[0141] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3-(3-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 25 are as follows:

[0142]

[0143] Methyl trans-2-(1,3-dithiadin-2-yl)-3-(3-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.30–7.27(m,2H),7.26–7.15(m,4H),7.13–7.09(m,1H),6.96(d,J=7.6Hz,1H),6.79(dd,J=8.3,2.6Hz,1H),5.36(s,1H ),4.25(d,J=1.8Hz,1H),3.78(s,3H),3.74(s,3H),3.51(d,J=1.7Hz,1H),3 .09–2.95(m,2H),2.93–2.83(m,2H),2.19–2.09(m,1H),2.00–1.86(m,1H). 13 CNMR(101MHz,Chloroform-d)δ172.6,159.5,146.5,139.9,135.1,133.8,129.4,1 28.9,127.3,127.3,120.6,114.7,113.6,55.4,53.1,52.2,48.7,45.2,31.1,25.3.

[0144] Preparation of methyl trans-2-(1,3-dithiadin-2-yl)-3-(4-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 26:

[0145] In a 25 mL round-bottom flask, 2-((4-methoxyphenyl)ethynyl)-1,3-dithiane (75 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 60%.

[0146] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3-(4-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 26 are as follows:

[0147]

[0148] Methyl trans-2-(1,3-dithiadin-2-yl)-3-(4-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.42–7.36(m,2H),7.31–7.25(m,3H),7.25–7.18(m,2H),6.84–6.78(m,2H),5.35(s,1H),4.22(d,J=1.7 Hz,1H),3.77(s,3H),3.76(s,3H),3.48(t,J=1.2Hz,1H),3.10–2.96(m,2H),2.93–2.81(m,2H),2.18–2.07(m,1H),2.04–1.88(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.9,159.8,145.9,140.1,132.0,129.8,128. 8,127.3,127.3,125.5,113.9,55.3,53.1,52.2,48.6,45.3,31.1,31.0,25.2.

[0149] Preparation of the product trans-3-(4-(tert-butyl)phenyl)-2-(1,3-dithiadin-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 27:

[0150] In a 25 mL round-bottom flask, 2-((4-(tert-butyl)phenyl)ethynyl)-1,3-dithiane (83 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and sodium methoxide (4 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 62%.

[0151] The structure and NMR data of the product trans-3-(4-(tert-butyl)phenyl)-2-(1,3-dithiadin-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 27 are as follows:

[0152]

[0153] Methyl trans-3-(4-(tert-butyl)phenyl)-2-(1,3-dithiadin-2-yl)-4-phenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.40–7.35(m,2H),7.32(d,J=2.2Hz,1H),7.31–7.27(m,4H),7.24–7.19(m,1H),5.39(s,1H),4.23(d,J= 1.8Hz,1H),3.77(s,3H),3.54–3.46(m,1H),3.11–2.95(m,2H),2.93–2.82(m,2H),2.22–2.09(m,1H),2.04–1.86(m,1H),1.27(s,9H). 13 C NMR(101MHz,Chloroform-d)δ172.8,151.7,146.2,140.2,133.8,129.9,128.9,1 27.9,127.3,127.3,125.4,53.2,52.2,48.6,45.3,34.8,31.3,31.0,31.0,25.2.

[0154] Preparation of methyl trans-2-(1,3-dithiadin-2-yl)-3-(4-fluorophenyl)-4-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 28:

[0155] In a 25 mL round-bottom flask, 2-((4-fluorophenyl)ethynyl)-1,3-dithiane (73 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 63%.

[0156] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3-(4-fluorophenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 28 are as follows:

[0157]

[0158] Methyl trans-2-(1,3-dithiadin-2-yl)-3-(4-fluorophenyl)-4-phenylcyclobut-2-ene-1-carboxylate 1 HNMR(400MHz,Chloroform-d)δ7.47–7.41(m,2H),7.31–7.26(m,2H),7.25–7.20(m,3H),7.00–6.95(m,2H),5.32(s,1H),4.23(d ,J=1.7Hz,1H),3.78(s,3H),3.50(d,J=1.7Hz,1H),3.09–2.96(m,2H),2.93–2.85(m,2H),2.20–2.09(m,1H),2.04–1.91(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.6,162.7(d,J=249.5Hz),145.4,139.7,134.2,130.3(d,J= 8.3Hz), 128.9, 128.8, 127.5, 127.3, 115.5 (d, J = 21.7Hz), 53.1, 52.3, 48.6, 45.0, 31.0, 25.2.

[0159] Preparation of ethyl trans-3-(4-chlorophenyl)-2-(1,3-dithiadin-2-yl)-4-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 29:

[0160] In a 25 mL round-bottom flask, 2-((4-chlorophenyl)ethynyl)-1,3-dithiane (76 mg, 0.3 mmol), the corresponding cinnamic ester compound (106 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 63%.

[0161] The structure and NMR data of the product trans-3-(4-chlorophenyl)-2-(1,3-dithiadin-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid ethyl ester obtained in Example 29 are as follows:

[0162]

[0163] Ethyl trans-3-(4-chlorophenyl)-2-(1,3-dithiadin-2-yl)-4-phenylcyclobut-2-ene-1-carboxylate 1 HNMR(600MHz,Chloroform-d)δ7.41(d,J=8.6Hz,2H),7.30–7.26(m,2H),7.26–7.21(m,5H),5.30(s,1H),4.32–4.18(m,3H) ,3.47(d,J=1.7Hz,1H),3.07–2.95(m,2H),2.94–2.85(m,2H),2.17–2.10(m,1H),2.02–1.91(m,1H),1.32(t,J=7.1Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ171.9,145.3,139.7,135.5,134.5,131.0,129. 7,128.9,128.7,127.4,127.3,61.2,53.5,48.5,45.1,31.1,31.1,25.2,14.4.

[0164] Preparation of trans-2-(1,3-dithiadin-2-yl)-3-(4-(fluorooxy)phenyl)-4-phenylcyclobut-2-ene-1-carboxylate-difluoro(1 / 1) obtained in Example 30:

[0165] In a 25 mL round-bottom flask, 2-((4-(trifluoromethoxy)phenyl)ethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (106 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 65%.

[0166] The structure and NMR data of the product trans-2-(1,3-dithiadin-2-yl)-3-(4-(fluorooxy)phenyl)-4-phenylcyclobut-2-ene-1-carboxylate-difluoro(1 / 1) obtained in Example 30 are as follows:

[0167]

[0168] Methyl trans-2-(1,3-dithiadin-2-yl)-4-phenyl-3-(4-(trifluoromethoxy)phenyl)cyclobut-2-ene-1-carboxylic acid 1 H NMR(400MHz,Chloroform-d)δ7.53–7.47(m,2H),7.33–7.27(m,2H),7.26(s,1H),7.24(q,J=2.0,1.5Hz,2H),7.15–7.10(m,2H),5.32(s,1 H),4.24(d,J=1.8Hz,1H),3.78(s,3H),3.51(d,J=2.3Hz,1H),3.09–2.96(m,2H),2.93–2.83(m,2H),2.19–2.11(m,1H),2.05–1.90(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.4,149.1,145.1,139.5,135.7,131.2,129.9,129 .0,127.6,127.2,120.8,120.5(d,J=259.7Hz),53.3,52.3,48.6,45.0,31.0,25.2.

[0169] Preparation of methyl trans-3-(benzodioxacyclopenten-5-yl)-2-(1,3-dithiadin-2-yl)-4-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 31:

[0170] In a 25 mL round-bottom flask, 5-((1,3-dithiaran-2-yl)ethynyl)benzodioxane (78 mg, 0.3 mmol), the corresponding cinnamic ester (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 52%.

[0171] The structure and NMR data of the product trans-3-(benzodioxacyclopenten-5-yl)-2-(1,3-dithiadin-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 31 are as follows:

[0172]

[0173] Methyl trans-3-(benzodioxacyclopenten-5-yl)-2-(1,3-dithiadin-2-yl)-4-phenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.31–7.26(m,2H),7.25–7.19(m,3H),7.07(d,J=1.7Hz,1H),6.86(dd,J=8.1,1.7Hz,1H),6.70(d,J=8.1Hz,1H),5.93(s,2 H),5.33(s,1H),4.19(d,J=1.7Hz,1H),3.77(s,3H),3.46(d,J=1.7Hz,1H), 3.05–2.96(m,2H),2.90–2.83(m,2H),2.17–2.09(m,1H),2.02–1.90(m,1H). 13 C NMR(101MHz,Chloroform-d)δ172.8,147.9,147.7,145.9,139.9,132.7,128.9,127.4 ,127.3,126.9,122.7,108.6,108.4,101.3,53.0,52.2,48.7,45.1,31.1,31.0,25.2.

[0174] Preparation of ethyl trans-2-(1,3-dithiadin-2-yl)-3-(6-methoxynaphthyl-2-yl)-4-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 32:

[0175] In a 25 mL round-bottom flask, 2-((7-methoxynaphthyl-2-yl)ethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate ester (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium methoxide (4 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 51%.

[0176] The structure and NMR data of the product trans-2-(1,3-dithiaran-2-yl)-3-(6-methoxynaphthyl-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid ethyl ester obtained in Example 32 are as follows:

[0177]

[0178] Ethyl trans-2-(1,3-dithiadin-2-yl)-3-(6-methoxynaphthyl-2-yl)-4-phenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.65(s,1H),7.63–7.58(m,2H),7.57–7.52(m,1H),7. 23–7.18(m,4H),7.16–7.11(m,1H),7.03–6.96(m,2H),5.37(s,1H),4.28(d,J=1.8Hz ,1H),4.19(qd,J=7.1,1.3Hz,2H),3.82(s,3H),3.45(d,J=1.7Hz,1H),3.06–2.89(m, 2H),2.88–2.76(m,2H),2.16–2.03(m,1H),1.95–1.84(m,1H),1.26(t,J=7.1Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ172.4,158.4,146.4,140.3,134.5,134.2,130.2,128.9,128.6,128. 2,127.8,127.4,127.3,126.9,126.4,119.1,105.9,61.1,55.5,53.5,48.7,45.4,31.1,25.4,14.5.

[0179] Preparation of ethyl trans-2-(bis(ethylthio)methyl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylate, the product obtained in Example 33:

[0180] In a 25 mL round-bottom flask, (3-phenylprop-2-yn-1,1-diyl)bis(ethyl thione) (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMF were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium ethoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 10 min. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 38%.

[0181] The structure and NMR data of the product trans-2-(bis(ethylthio)methyl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester obtained in Example 33 are as follows:

[0182]

[0183] Ethyl trans-2-(bis(ethylthio)methyl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.39–7.26(m,5H),6.48(s,2H),5.12(s,1H),4.26–4.18(m,3H),3.81(s,3 H),3.77(s,6H),3.48(t,J=1.2Hz,1H),2.85–2.62(m,4H),1.32(t,J=7.3Hz,6H),1.25(t,J=7.4Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ172.7,153.5,144.9,137.2,137.1,136.2,132.9,128.6, 128.5,127.7,104.1,61.1,61.0,56.1,53.0,47.9,46.1,26.9,26.4,14.7,14.4,14.3.

[0184] Preparation of methyl trans-2-(2-decyl-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylate, the product obtained in Example 34:

[0185] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Then, nonane (152 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 68%.

[0186] The structure and NMR data of the product trans-2-(2-decyl-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-en-1-carboxylic acid methyl ester obtained in Example 34 are as follows:

[0187]

[0188] Methyl trans-2-(2-decyl-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid 1 H NMR(600MHz,Chloroform-d)δ7.74–7.68(m,2H),7.29–7.27(m,1H),7.26–7.22(m,2H),7.13(d,J=7.5Hz ,1H),7.07(td,J=7.1,2.1Hz,1H),7.05–6.99(m,2H),4.48(d,J=1.8Hz,1H),3.72(s,3H),3.25(d,J=1.9 Hz,1H),3.00–2.94(m,1H),2.63–2.54(m,2H),2.41(dt,J=14.3,4.1Hz,1H),2.32(s,3H),2.03–1.98(m, 2H),1.97–1.92(m,1H),1.87–1.78(m,1H),1.77–1.70(m,1H),1.30–1.21(m,13H),0.87(t,J=7.0Hz,3H). 13C NMR(151MHz,Chloroform-d)δ173.9,147.4,140.4,139.0,136.7,133.8,130.3,129.4,128.3,127.8,126.8,126 .3,126.1,54.2,53.2,52.1,43.4,40.4,32.0,29.8,29.6,29.5,29.4,28.4,27.9,24.9,24.4,22.8,19.6,14.3.

[0189] Preparation of methyl trans-2-(2-(oxetane-3-yl)-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylate, the product obtained in Example 35:

[0190] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Next, 3-iodooxyhexacyclobutane (110 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 56%.

[0191] The structure and NMR data of the product trans-2-(2-(oxetane-3-yl)-1,3-dithia-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 35 are as follows:

[0192]

[0193] trans-2-(2-(oxecyclobutan-3-yl)-1,3-dithiapan-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1H NMR(400MHz,Chloroform-d)δ7.71–7.65(m,2H),7.30–7.26(m,2H),7.26–7.22(m,1H),7.15–7.11(m,1H),7.08(td,J=7 .3,1.6Hz,1H),7.01(td,J=7.4,1.7Hz,1H),6.95(dd,J=7.6,1.5Hz,1H),5.05(t,J=6.7Hz,1H),4.98(t,J=6.8Hz,1H),4. 70(dd,J=8.3,6.5Hz,1H),4.63(dd,J=8.5,6.6Hz,1H),4.42(d,J=1.8Hz,1H),3.73(s,3H),3.72–3.62(m,1H),3.25(d,J= 1.8Hz,1H),3.08–2.96(m,1H),2.72–2.59(m,2H),2.50–2.41(m,1H),2.29(s,3H),2.03–1.94(m,1H),1.87–1.75(m,1H). 13 C NMR(101MHz,Chloroform-d)δ173.7,148.4,139.5,138.5,136.7,133.6,130.4,129.4,128.5, 127.9,126.9,126.4,125.9,72.8,72.4,54.9,53.7,52.2,43.7,43.4,27.8,27.6,24.5,19.6.

[0194] Preparation of methyl trans-2-(2-benzyl-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylate, the product obtained in Example 36:

[0195] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Benzyl bromide (103 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was complete, saturated brine was added to quench the reaction mixture, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 58%.

[0196] The structure and NMR data of the product trans-2-(2-benzyl-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-en-1-carboxylic acid methyl ester obtained in Example 36 are as follows:

[0197]

[0198] Methyl trans-2-(2-benzyl-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid 1 H NMR(600MHz,Chloroform-d)δ7.36–7.33(m,3H),7.16–7.08(m,3H),7.08–7.03(m,2H),7.01–6.9 6(m,3H),6.76(d,J=7.6Hz,1H),4.50(d,J=1.9Hz,1H),3.75(s,4H),3.42(d,J=2.0Hz,1H),3.27( d,J=2.1Hz,2H),3.04(ddd,J=14.8,12.6,2.6Hz,1H),2.56(dt,J=14.2,3.8Hz,1H),2.41(tt,J=1 2.6, 2.7Hz, 1H), 2.32 (s, 3H), 2.30–2.24 (m, 1H), 1.96–1.90 (m, 1H), 1.78 (qt, J=12.8, 3.2Hz, 1H). 13 C NMR(151MHz,Chloroform-d)δ174.0,149.5,138.7,138.2,136.8,134.8,133.4,131.4,130.3,129.3,1 28.1,128.1,127.6,127.3,126.9,126.8,126.0,54.8,53.3,52.2,46.3,43.5,28.9,27.7,24.5,19.6.

[0199] Preparation of methyl trans-2-(2-(2-methylallyl)-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-en-1-carboxylic acid obtained in Example 37:

[0200] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Next, 3-bromo-2-methylpropene (81 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 58%.

[0201] The structure and NMR data of the product trans-2-(2-(2-methylallyl)-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-en-1-carboxylic acid methyl ester obtained in Example 37 are as follows:

[0202]

[0203] Methyl trans-2-(2-(2-methylallyl)-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid 1 H NMR(400MHz,Chloroform-d)δ7.76–7.66(m,2H),7.30–7.27(m,1H),7.26–7.24(m,1H),7.14– 7.04(m,3H),6.99–6.94(m,2H),5.00(p,J=1.6Hz,1H),4.98–4.94(m,1H),4.51(d,J=2.0Hz,1H ),3.73(s,3H),3.36(d,J=1.9Hz,1H),3.03–2.96(m,1H),2.84–2.73(m,2H),2.62–2.51(m,2H) ,2.40–2.34(m,1H),2.32(s,3H),1.97(t,J=1.1Hz,3H),1.94–1.88(m,1H),1.86–1.77(m,1H). 13C NMR(101MHz,Chloroform-d)δ173.9,147.2,140.4,140.3,138.7,136.7,133.8,130.3,129.5,128 .3,127.8,126.7,126.5,126.1,117.1,53.4,53.3,52.1,48.0,43.2,28.6,28.3,24.8,24.5,19.6.

[0204] Preparation of methyl trans-2-(2-(but-2-yn-1-yl)-1,3-dithiaalkyl-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-en-1-carboxylic acid obtained in Example 38:

[0205] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Then, 1-bromo-2-butyne (80 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 48%.

[0206] The structure and NMR data of the product trans-2-(2-(but-2-yn-1-yl)-1,3-dithiaalkyl-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-en-1-carboxylic acid methyl ester obtained in Example 38 are as follows:

[0207]

[0208] Methyl trans-2-(2-(but-2-yn-1-yl)-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylate 1H NMR(400MHz,Chloroform-d)δ7.81–7.75(m,2H),7.28–7.26(m,1H),7.28–7.20(m,4H),7.19(dd,J=7.6,1.5 Hz,1H),7.12(dd,J=7.6,1.6Hz,1H),7.06(td,J=7.3,1.5Hz,2H),7.00(td,J=7.5,1.6Hz,1H),4.49(d,J=1.8 Hz,1H),3.71(s,3H),3.35(d,J=1.8Hz,1H),3.02–2.93(m,1H),2.90(q,J=2.5Hz,2H),2.72–2.60(m,1H),2.5 6–2.48(m,1H),2.47–2.39(m,1H),2.33(s,3H),1.99–1.90(m,1H),1.85(t,J=2.6Hz,3H),1.82–1.75(m,1H). 13 C NMR(101MHz,Chloroform-d)δ173.8,149.1,139.0,138.7,136.6,133.7,130.2,129.7,128.3,12 7.6,126.7,126.5,126.2,79.9,74.1,53.1,52.9,52.1,43.6,31.6,28.6,27.9,24.4,19.7,3.9.

[0209] Preparation of methyl trans-3-phenyl-2-(2-(2-(benzenesulfonyl)ethyl)-1,3-dithiaalkyl-2-yl)-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid obtained in Example 39:

[0210] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Then, phenyl vinyl sulfone (100 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 50%.

[0211] The structure and NMR data of the product trans-3-phenyl-2-(2-(2-(benzenesulfonyl)ethyl)-1,3-dithiaalkyl-2-yl)-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 39 are as follows:

[0212]

[0213] Methyl trans-3-phenyl-2-(2-(2-(benzenesulfonyl)ethyl)-1,3-dithiaalkyl-2-yl)-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid 1 H NMR(400MHz,Chloroform-d)δ7.79–7.71(m,2H),7.57–7.50(m,3H),7.40(t,J=7.8Hz,2H),7.23(d d,J=5.1,1.9Hz,3H),7.16–7.08(m,2H),7.02(td,J=7.4,1.7Hz,1H),6.92(dd,J=7.6,1.4Hz,1H), 4.32(d,J=1.8Hz,1H),3.69(s,3H),3.55–3.44(m,1H),3.39–3.29(m,1H),3.13(d,J=1.8Hz,1H),2 .83(dd,J=6.9,4.5Hz,2H),2.66–2.61(m,2H),2.60–2.48(m,2H),2.27(s,3H),1.95–1.87(m,2H). 13 C NMR(101MHz,Chloroform-d)δ173.4,148.3,138.8,138.3,138.2,136.7,133.7,133.0,130.5,129.3,129 .0,128.8,128.2,128.0,127.1,126.4,126.0,52.9,52.5,52.2,52.0,44.2,31.4,27.9,27.2,24.2,19.5.

[0214] Preparation of methyl trans-2-(2-(4-methoxybenzoyl)-1,3-dithiaalkyl-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid obtained in Example 40:

[0215] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Then, p-methoxybenzoyl chloride (100 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 45%.

[0216] The structure and NMR data of the product trans-2-(2-(4-methoxybenzoyl)-1,3-dithiaalkyl-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 40 are as follows:

[0217]

[0218] Methyl trans-2-(2-(4-methoxybenzoyl)-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid 1 H NMR(400MHz,Chloroform-d)δ8.15–8.06(m,2H),7.16–7.05(m,7H),6.92(dd,J=8.2 ,6.7Hz,1H),6.71(d,J=7.7Hz,1H),6.69–6.63(m,2H),4.43(d,J=1.9Hz,1H),3.88( s,3H),3.76(s,3H),3.66(d,J=1.8Hz,1H),3.61–3.52(m,1H),3.16(t,J=13.2Hz,1H ),2.69(tt,J=10.4,3.8Hz,2H),2.33(s,3H),2.13–2.07(m,1H),1.97–1.87(m,1H). 13C NMR(101MHz,Chloroform-d)δ191.8,174.0,162.8,148.4,137.7,136.4,134.6,132.7,132.2,130.3,128. 7,128.1,128.1,127.2,127.1,126.7,126.3,112.7,58.4,55.5,52.7,52.4,45.4,28.9,27.6,23.8,19.6.

[0219] Preparation of methyl trans-2-(2-(2-chloropyridin-4-yl)-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid obtained in Example 41:

[0220] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Next, 2-chloro-4-fluoropyridine (79 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 45%.

[0221] The structure and NMR data of the product trans-2-(2-(2-chloropyridin-4-yl)-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-en-1-carboxylic acid methyl ester obtained in Example 41 are as follows:

[0222]

[0223] Methyl trans-2-(2-(2-chloropyridin-4-yl)-1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid 1H NMR(400MHz,Chloroform-d)δ8.32(d,J=5.3Hz,1H),7.95(d,J=1.7Hz,1H),7.81(dd,J=5.3,1.7Hz,1H),7.59–7.50(m,2H),7.25–7.20(m,3H),7.17–7.11( m,2H),7.08–7.01(m,2H),4.37(d,J=1.8Hz,1H),3.62(s,3H),3.28(d,J=1.8H z,1H),2.94–2.80(m,3H),2.67–2.59(m,1H),2.29(s,3H),2.12–2.00(m,2H). 13 C NMR(101MHz,Chloroform-d)δ173.1,152.8,152.3,150.0,148.5,138.2,136.8,136.5,132.1,130.5,1 29.8,128.8,127.9,127.2,126.5,126.1,125.1,123.2,56.0,53.8,52.2,44.5,29.0,28.7,23.8,19.6.

[0224] Preparation of methyl trans-2-(2-cyclopentyl-1,3-dithiadin-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 42:

[0225] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Then, iodocyclopentane (117 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 57%.

[0226] The structure and NMR data of the product trans-2-(2-cyclopentyl-1,3-dithiaalkyl-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 42 are as follows:

[0227]

[0228] Methyl trans-2-(2-cyclopentyl-1,3-dithiadin-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ7.71–7.63(m,2H),7.26–7.20(m,3H),7.20–7.14(m,1H),6 .95(dt,J=7.6,1.3Hz,1H),6.89–6.80(m,2H),4.31(d,J=1.9Hz,1H),3.70(s,3H),3.37(d ,J=1.9Hz,1H),2.99–2.89(m,1H),2.52–2.44(m,2H),2.43–2.37(m,1H),2.24(dt,J=14.0 ,3.8Hz,1H),2.07–1.96(m,2H),1.93–1.82(m,3H),1.77–1.68(m,3H),1.66–1.58(m,2H). 13 C NMR(101MHz,Chloroform-d)δ163.1(d,J=246.0Hz),147.5,143.1(d,J=6.9Hz),141.3,133.5,130.2(d,J=8.3Hz),129.3,128.4,127.7,123.2 (d,J=2.9Hz),114.3(d,J=21.3Hz),114.0(d,J=21.1Hz),59.0,53.2,52.2,48.3,46.7(d,J=1.9Hz),28.6,28.1,28.0,27.4,26.6,26.4,24.9.

[0229] Preparation of the product trans-2-(2-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-1,3-dithiaalkyl-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 43:

[0230] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Next, 5-(2-bromoethyl)-2,3-dihydrobenzofuran (136 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 55%.

[0231] The structure and NMR data of the product trans-2-(2-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-1,3-dithiaalkyl-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 43 are as follows:

[0232]

[0233] trans-2-(2-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-1,3-dithiapan-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1 H NMR(400MHz,Chloroform-d)δ7.69–7.61(m,2H),7.23(d,J=5.0Hz,2H),7.15(d,J=8.1Hz,2H),7.07(d,J=7.8H z,2H),6.84(d,J=1.7Hz,1H),6.79(dd,J=8.2,1.9Hz,1H),6.65(d,J=8.1Hz,1H),4.52(t,J=8.6Hz,2H),4.23(d ,J=1.8Hz,1H),3.71(s,3H),3.49(d,J=1.8Hz,1H),3.13(t,J=8.6Hz,2H),2.98–2.88(m,2H),2.86–2.78(m,1H ),2.74–2.66(m,2H),2.63–2.53(m,1H),2.40–2.31(m,2H),2.29(s,3H),2.04–1.94(m,1H),1.95–1.85(m,1H). 13C NMR(101MHz,Chloroform-d)δ173.4,158.5,148.6,139.9,137.2,136.8,133.7,133.6,129.5,129.3,128.3,12 8.0,127.9,127.3,127.2,125.1,109.1,71.3,53.9,53.7,52.1,47.6,42.3,30.8,29.9,28.1,27.7,24.8,21.2.

[0234] Preparation of methyl trans-2-(2-(2-methylpyrimidin-4-yl)-1,3-dithiadin-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylic acid obtained in Example 44:

[0235] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Next, 4-fluoro-2-methylpyrimidine (66 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 55%.

[0236] The structure and NMR data of the product trans-2-(2-(2-methylpyrimidin-4-yl)-1,3-dithiadin-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-en-1-carboxylic acid methyl ester obtained in Example 44 are as follows:

[0237]

[0238] Methyl trans-2-(2-(2-methylpyrimidin-4-yl)-1,3-dithiadin-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylic acid 1H NMR(400MHz,Chloroform-d)δ8.40(d,J=5.3Hz,1H),7.63(d,J=5.4Hz,1H),7.25–7.21(m,2H),7.20–7.15(m,2H),7.11–7.04(m,5H),4.14(d,J =1.7Hz,1H),3.74(s,3H),3.70(d,J=1.7Hz,1H),3.64–3.55(m,1H),2. 95–2.88(m,1H),2.81(d,J=4.6Hz,5H),2.29(s,3H),2.14–2.04(m,2H). 13 CNMR(101MHz,Chloroform-d)δ173.6,169.4,167.0,157.4,148.4,137.5,137.0,136.7,131.9, 129.6,128.8,128.6,127.8,127.3,117.2,56.3,54.0,52.3,48.1,29.3,27.7,26.4,24.0,21.2.

[0239] Preparation of ethyl trans-2-(2-(4-nitrophenyl)-1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 45:

[0240] In a 25 mL round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamic ester compound (97 mg, 0.6 mmol), and 6 mL of DMSO were added sequentially. Then, potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added, and the mixture was stirred at 50 °C for 5 min. Subsequently, p-fluoronitrobenzene (126 mg, 0.9 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added, and the mixture was stirred for 1 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, saturated brine was added to the reaction system to quench the reaction, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 58%.

[0241] The structure and NMR data of the product trans-2-(2-(4-nitrophenyl)-1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ethyl ester obtained in Example 45 are as follows:

[0242]

[0243] Ethyl trans-2-(2-(4-nitrophenyl)-1,3-dithiaalkyl-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate 1 H NMR(400MHz,Chloroform-d)δ8.17(m,4H),7.40(m,2H),7.29(m,3H),7.23(m,2H),7.14(m,3H),4.15(d,J=1 .7Hz,1H),4.06(m,2H),3.48(d,J=1.7Hz,1H),2.93(m,3H),2.66(m,1H),2.08(m,2H),1.19(t,J=7.1Hz,3H). 13 CNMR(101MHz,Chloroform-d)δ172.3,148.2,147.7,147.3,140.1,138.5,132.1,130.7,129. 6,129.0,128.6,127.7,127.4,127.3,123.5,61.1,56.7,54.9,48.2,29.2,28.9,23.9,14.2.

[0244] Preparation of methyl trans-2-formyl-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid obtained in Example 46:

[0245] In a 25 mL round-bottom flask, methyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid (40 mg, 0.1 mmol), 9 mL acetonitrile, and 1 mL water were added. Then, benzene (65, 0.15 mmol) was added at 0 °C. The mixture was stirred at room temperature for 20 min, and the reaction was monitored by thin-layer chromatography. After the reaction was completed, water was added to quench the reaction mixture, and the mixture was extracted three times with ethyl acetate (15 mL). The organic phases were combined, washed three times with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography with a yield of 85%.

[0246] The structure and NMR data of the product trans-2-formyl-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 46 are as follows:

[0247]

[0248] Methyl trans-2-formyl-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylate 1H NMR(400MHz,Chloroform-d)δ10.13(s,1H),7.65–7.60(m,2H),7.47–7.41(m,1H),7.38(dd,J=8.2,6.5Hz,2H),7.22(dd,J=7.7,1.5Hz,1H),7.15(td ,J=7.4,1.4Hz,1H),7.04(td,J=7.5,1.5Hz,1H),6.94(dd,J=7.7,1.4Hz,1 H), 4.64 (d, J = 2.1Hz, 1H), 3.78 (s, 3H), 3.52 (d, J = 2.1Hz, 1H), 2.42 (s, 3H). 13 C NMR(101MHz,Chloroform-d)δ185.0,172.3,160.2,137.0,136.4,134.9,131 .8,131.6,130.7,129.2,129.1,127.6,126.6,126.6,52.4,50.0,45.9,19.7.

[0249] Preparation of methyl trans-4-(3-fluorophenyl)-2-methyl-3-phenylcyclobut-2-ene-1-carboxylate, the product obtained in Example 47:

[0250] In a 25 mL round-bottom flask, methyl trans-2-(1,3-dithiadin-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid (40 mg, 0.1 mmol) and 8 mL of tetrahydrofuran were added, followed by the addition of excess Raney nickel. The mixture was stirred at room temperature for 3 hours, and the reaction was monitored by thin-layer chromatography. After the reaction was complete, the mixture was filtered through a diatomaceous earth filter and washed with ethyl acetate. The filtrate was extracted three times with ethyl acetate (15 mL), and the organic phases were combined. The organic phases were washed three times with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography in 89% yield.

[0251] The structure and NMR data of the product trans-4-(3-fluorophenyl)-2-methyl-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester obtained in Example 47 are as follows:

[0252]

[0253] methyl trans-4-(3-fluorophenyl)-2-methyl-3-phenylcyclobut-2-ene-1-carboxylate 1H NMR(400MHz,Chloroform-d)δ7.29(dt,J=6.8,1.3Hz,1H),7.26–7.18(m,4H),7.05(dt,J=7.6,1.3Hz,1H),6.95(dt,J =9.9,2.1Hz,1H),6.93–6.87(m,1H),4.29(p,J=2.1Hz,1H),3.76(s,3H),3.26(p,J=1.6Hz,1H),2.16(t,J=1.8Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ172.7,163.3(d,J=245.8Hz),143.8(d,J=6.9Hz),141.5,137.1,133.9,130.2(d,J=8.3Hz),1 28.6, 127.6, 126.5, 123.1 (d, J = 2.9Hz), 114.01 (d, J = 21.2Hz), 113.97 (d, J = 21.1Hz), 55.0, 52.0, 47.7 (d, J = 1.8Hz), 14.9.

[0254] Preparation of methyl trans-2-methyl-3-phenyl-4-(o-tolyl)cyclobutane-1-carboxylate, the product obtained in Example 48:

[0255] In a 25 mL round-bottom flask, methyl trans-2-(1,3-dithiadin-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid (40 mg, 0.1 mmol) and 8 mL of tetrahydrofuran were added, followed by excess Raney nickel. The mixture was stirred at room temperature for 3 hours under a hydrogen atmosphere. The reaction was monitored by thin-layer chromatography. After the reaction was complete, the mixture was filtered through a diatomaceous earth filter and washed with ethyl acetate. The filtrate was extracted three times with ethyl acetate (15 mL), and the organic phases were combined. The organic phases were washed three times with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was then obtained by column chromatography in 85% yield.

[0256] The structure and NMR data of the product trans-2-methyl-3-phenyl-4-(o-tolyl)cyclobutane-1-carboxylate obtained in Example 48 are as follows:

[0257]

[0258] Methyl trans-2-methyl-3-phenyl-4-(o-tolyl)cyclobutane-1-carboxylate 1H NMR(400MHz,Chloroform-d)δ7.32(d,J=7.6Hz,1H),7.20(td,J=7.6,1.4Hz,1H),7.12–7.02(m,4H),6.98–6.89(m,3H),4.29(t,J=10.0Hz,1H),4.03(t,J=9.2Hz,1H),3.76(s,3H),3.58(t,J=10.3Hz,1H),3.24–3.08(m,1H),2.03(s,3H),0.78(d,J=7.0Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ174.9,138.2,137.7,136.4,130.2,129.7,127.7,126.4,126.1,125.7,52.0,48.2,47.8,43.1,35.4,19.9,15.7。

Claims

1. A 1,3-dithiane-substituted cyclobutene derivative, characterized in that, The compound has the following general formula (I): In formula (Ⅰ), R 1 The phenyl or naphthyl group is substituted, wherein the substituent for the phenyl group is selected from one or more of hydrogen, methyl, methoxy, fluorine, chlorine, and trifluoromethoxy; R 2 The substituted group is phenyl, furanyl, thiophene, or pyridyl, wherein the substituent of the phenyl group is selected from one or more of hydrogen, methyl, methoxy, fluorine, chlorine, bromine, and trifluoromethoxy; R 3 The derivatives are methyl, ethyl, n-butyl, cyclohexyl, benzyl, cyclododecyl, furan derivatives, adamantane derivatives, L-geraniol derivatives, and R-(-)-norbutan derivatives; E is hydrogen; X = oxygen (O) or sulfur (S).

2. The method for preparing a 1,3-dithiane-substituted cyclobutene derivative according to claim 1, characterized in that, The process includes the following steps: Under the action of a strong base, a 2-ethynyl-1,3-dithiane derivative (II), a cinnamic ester compound (III), and an electrophilic reagent are reacted in a suitable organic solvent and at a specific temperature to generate a cyclobutene compound (I). The chemical reaction equation is as follows: 。 3. The preparation method according to claim 2, characterized in that, The organic solvent is one of dimethyl sulfoxide, tetrahydrofuran, and N,N-dimethylformamide; the strong base is one of potassium tert-butoxide, sodium tert-butoxide, potassium ethoxide, sodium ethoxide, potassium methoxide, and sodium methoxide.

4. The preparation method according to claim 2, characterized in that, The electrophilic reagent is water, an alkyl halide, an aryl halide, an acyl halide, or a Michael acceptor.

5. The preparation method according to claim 2, characterized in that, The molar ratio of strong base, 2-ethynyl-1,3-dithiane derivative (II), cinnamic acid ester compound (III) to electrophilic reagent is (0.1-1.2):1:(1-3):(1-3).

6. The application of a 1,3-dithiane-substituted cyclobutene derivative according to claim 1 in the synthesis of aldehyde-substituted cyclobutene compounds, characterized in that, The process includes the following steps: adding a 1,3-dithiane-substituted cyclobutene derivative (I), acetonitrile, and water to a reaction vessel; adding [bis(trifluoroacetoxy)iodide]benzene at 0°C; and reacting at room temperature to obtain the target product IV. 。 7. The application of a 1,3-dithiane-substituted cyclobutene derivative according to claim 1 in the synthesis of methyl-substituted cyclobutene compounds, characterized in that, The process includes the following steps: adding tetrahydrofuran and a 1,3-dithiane-substituted cyclobutene derivative (I) to a reaction vessel, adding Raney nickel in portions, and reacting at room temperature to obtain the target product V. 。 8. The application of a 1,3-dithiane-substituted cyclobutene derivative according to claim 1 in the synthesis of polysubstituted cyclobutane compounds, characterized in that, The process includes the following steps: adding tetrahydrofuran, a 1,3-dithiane-substituted cyclobutene derivative (I) to a reaction vessel, adding Raney nickel in portions, and reacting at room temperature under a hydrogen atmosphere to obtain the target product VI. 。

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