1, 3-dithiane substituted cyclobutene derivative as well as preparation method and application thereof

Abstract

The invention belongs to the field of organic chemistry, and provides a 1, 3-dithiane substituted cyclobutene derivative as well as a preparation method and application thereof. According to the method, alkynyl thiane compounds and cinnamate compounds are taken as raw materials, and intermolecular cycloaddition is carried out under the promotion of alkali, so that the compound is obtained. And cyclobutene with a more complex structure can be obtained through negative ion relay chemistry. The compound is structurally characterized by having a structure as shown in a formula (I), wherein R1 and R2 are aryl groups; r3 is alkyl or aryl; x = oxygen (O) or sulfur (S); e is hydrogen, alkyl or aryl. According to the method provided by the invention, cheap strong base is used as an accelerant, a noble metal catalyst is not used, meanwhile, the reaction condition is mild, the operation is simple, the substrate applicability is wide, anhydrous and anaerobic operation is not needed, and the method has very strong practicability and industrial application prospects. The method provided by the invention can be used for synthesis and later modification of natural products, drug molecules and functional material molecules.

Description

Technical Field

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

[0002] The 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.). The unique ring strain and double bond characteristics of this type of skeleton give it a rich variety of functional groups, making it an important synthetic building block (Acc. Chem. Res. 2016, 49, 2444-2458. J. Am. Chem. Soc. 2024, 146, 12691-12701.).

[0003] Therefore, this type of skeleton shows important application value in many fields such as medicine, biology, and materials. However, so far, the synthesis of this type of skeleton is mainly achieved through 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, this type of method has obvious limitations, such as the use of expensive precious metal catalysts ruthenium, rhodium, palladium and gold; the reaction must be carried out in an anhydrous and oxygen-free atmosphere; an excess of oxidant must be used. Therefore, it is very valuable to develop a method for synthesizing cyclobutene compounds with non-precious metal catalysis, mild conditions, and simple operation.

[0004] As an aldehyde and ketone protecting group and polar conversion reagent, 1,3-dithiane 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.). Drug molecules substituted with 1,3-dithiane can consume ROS (reactive oxygen species) and reduce oxidative stress in vivo (ACS Nano.2022,16,21225-21239). At the same time, the introduced sulfur atom can change the lipid solubility, metabolic stability and bioavailability of drug molecules, thereby optimizing the pharmacokinetic properties of drugs. Summary of the invention

[0005] The purpose of the present invention is to provide a 1,3-dithiane substituted cyclobutene derivative and a preparation method and application thereof, that is, 2-ethynyl-1,3-dithiane derivative, cinnamate compound, suitable solvent, strong base and electrophilic reagent are sequentially added into a reactor, and a class of cyclobutene compounds are obtained by reaction at a suitable temperature. The method does not require precious metal catalysis, does not require anhydrous and oxygen-free operation, has mild conditions, wide substrate applicability, high stereoselectivity and high yield.

[0006] The present invention relates to a 1,3-dithiane-substituted cyclobutene derivative, characterized in that the compound has the following general formula (I):

[0007] In formula (I), R 1 is substituted phenyl (the substituent is selected from one or more of hydrogen, methyl, methoxy, fluorine, chlorine, trifluoromethoxy) or naphthyl; R 2 is substituted phenyl (the substituent is selected from one or more of hydrogen, methyl, methoxy, fluorine, chlorine, bromine, trifluoromethoxy), furyl, thienyl or pyridyl; R 3 is methyl, ethyl, n-butyl, cyclohexyl, benzyl, cyclododecyl, furan derivatives, adamantane derivatives, L-geraniol derivatives, R-(-)-nopol derivatives; 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-chloropyridin-4-yl, 2-methylpyrimidin-4-yl, 4-nitrophenyl; X = oxygen (O) or sulfur (S).

[0008] The present invention relates to a method for preparing a 1,3-dithiane-substituted cyclobutene derivative, which is characterized by comprising the following steps: reacting a 2-ethynyl-1,3-dithiane derivative (II), a cinnamate compound (III) and an electrophilic reagent in a suitable organic solvent and at a specific temperature under the action of a strong base to generate a cyclobutene compound (I), wherein the chemical reaction equation is as follows:

[0009] In the above technical solution, the organic solvent is one of dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), and N,N-dimethylformamide (DMF).

[0010] The strong base is one of potassium tert-butoxide, sodium tert-butoxide, potassium ethoxide, sodium ethoxide, potassium methoxide and sodium methoxide.

[0011] In the above technical solution, the electrophilic reagent is water, alkyl halide, aryl halide, acyl halide, Michael acceptor and the like.

[0012] In the above technical scheme, 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).

[0013] In the above technical scheme, the specific reaction steps include: adding 2-ethynyl-1,3-dithiane derivatives, cinnamate compounds, suitable solvents and strong bases to the reaction flask in sequence, stirring the reaction at 50°C for 1 to 10 minutes, then adding an electrophilic reagent and continuing to stir, monitoring the reaction by thin layer chromatography, and slowly adding saturated brine to the reaction system to quench the reaction after the raw materials are completely consumed, and extracting three times with ethyl acetate (15 ml), combining the organic phases, washing the organic phases three times with saturated brine (40 ml), drying over anhydrous sodium sulfate, filtering, removing volatiles under vacuum, and obtaining the product by column chromatography. DETAILED DESCRIPTION

[0014] The following examples can help those skilled in the art to more fully understand the present invention, but they do not limit the present invention in any way. The raw materials used in the present invention are all known compounds, which can be purchased from the market or synthesized using methods known in the art.

[0015] Example 1: Preparation of compound trans-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ethyl ester:

[0016] In a 25 ml round-bottom flask, 2-(phenylethynyl)-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, and then potassium phosphate (13 mg, 0.06 mmol) and sodium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 72%.

[0017] The structure and NMR data of the product obtained in Example 1, trans-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ethyl ester are as follows:

[0018]

[0019] trans-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ethyl ester 1 H NMR(400MHz,Chloroform-d)δ7.48–7.43(m,2H),7.27(d,J=8.1Hz,4H),7.25(t,J=2.2Hz,4H),5.38(s,1H),4.30–4.18(m,3H ),3.49(d,J=1.8Hz,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=7.1Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ172.2,146.2,140.1,134.9,132.7,128.8,128.5,128.4,128.2,127.3,127.3,61.0,53.4,48.7,45.3,31.0,25.3,14.4.

[0020] Example 2: Preparation of the compound trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0021] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (105 mg, 0.6 mmol) and 6 ml of DMF were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and sodium tert-butoxide (30 mg, 0.6 mmol) were added and 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 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 obtained by column chromatography with a yield of 68%.

[0022] The structure and NMR data of the product obtained in Example 2, trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0023]

[0024] trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1HNMR(400MHz,Chloroform-d)δ7.49–7.44(m,2H),7.36–7.30(m,2H),7.30–7.2 7(m,1H),7.18(dd,J=7.7,1.3Hz,1H),7.15–7.10(m,1H),7.07–7.02(m,2H),5. 41(s,1H),4.52(d,J=1.9Hz,1H),3.80(s,3H),3.41(d,J=0.9Hz,1H),3.10–2.9 5(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(101MHz,Chloroform-d)δ173.1,145.9,138.1,136.3,134.6,132.7,130.4,12 8.6,128.5,128.2,127.0,126.4,126.3,52.7,52.2,45.2,44.9,30.9,25.1,19.6.

[0025] Example 3 Preparation of the obtained product trans-2-(1,3-dithiane-2-yl)-4-(2-methoxyphenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0026] 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 added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium ethoxide (5 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 69%.

[0027] The structure and NMR data of the product obtained in Example 3, trans-2-(1,3-dithiane-2-yl)-4-(2-methoxyphenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0028]

[0029] trans-2-(1,3-dithian-2-yl)-4-(2-methoxyphenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 1H 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.

[0030] Example 4 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0031] In a 25 ml round-bottom flask, 2-(phenylethynyl)-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, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 62%.

[0032] The structure and NMR data of the product obtained in Example 4, trans-2-(1,3-dithiane-2-yl)-4-(2-methoxyphenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0033]

[0034] trans-2-(1,3-dithian-2-yl)-4-(2-methoxyphenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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.

[0035] Example 5 Preparation of the obtained product trans-2-(1,3-dithiane-2-yl)-4-(4-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0036] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (108 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and sodium ethoxide (5 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 62%.

[0037] The structure and NMR data of the product obtained in Example 5, trans-2-(1,3-dithiane-2-yl)-4-(4-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0039]

[0040] trans-2-(1,3-dithian-2-yl)-4-(4-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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.

[0041] Example 6 Preparation of the product trans-4-(4-chlorophenyl)-2-(1,3-dithian-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0042] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (117 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 58%.

[0043] The structure and NMR data of the product obtained in Example 6, trans-4-(4-chlorophenyl)-2-(1,3-dithiane-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0044]

[0045] trans-4-(4-chlorophenyl)-2-(1,3-dithian-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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.

[0046] Example 7 Preparation of the product trans-4-(4-bromophenyl)-2-(1,3-dithian-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0047] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (143 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and sodium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 59%.

[0048] The structure and NMR data of the product obtained in Example 7, trans-4-(4-bromophenyl)-2-(1,3-dithian-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0049]

[0050] trans-4-(4-bromophenyl)-2-(1,3-dithian-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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.

[0051] Example 8 Preparation of the product trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(4-(trifluoromethyl)phenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester:

[0052] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (146 mg, 0.6 mmol) and 6 ml of THF were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 58%.

[0053] The structure and NMR data of the product obtained in Example 8, trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(4-(trifluoromethyl)phenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester, are as follows:

[0054]

[0055] trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(4-(trifluoromethyl)phenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester 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.

[0056] Example 9 Preparation of the product trans-2-(1,3-dithiane-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0057] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (108 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 78%.

[0058] The structure and NMR data of the product obtained in Example 9, trans-2-(1,3-dithiane-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0060]

[0061] trans-2-(1,3-dithian-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester1 HNMR(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.

[0062] Example 10 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester:

[0063] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (160 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 53%.

[0064] The structure and NMR data of the product obtained in Example 10, trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester, are as follows:

[0065]

[0066] trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester 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.

[0067] Preparation of the product obtained in Example 11: trans-benzyl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate:

[0068] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (143 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 56%.

[0069] The structure and NMR data of the product trans-benzyl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate obtained in Example 11 are as follows:

[0070]

[0071] trans-Benzyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate 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.

[0072] Example 12 Preparation of the product trans-cyclohexyl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate:

[0073] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (138 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 53%.

[0074] The structure and NMR data of the product obtained in Example 12, trans-cyclohexyl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate, are as follows:

[0076]

[0077] Trans-cyclohexyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate. 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.

[0078] Example 13 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-ene-1-carboxylic acid ethyl ester:

[0079] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (160 mg, 0.9 mmol) and 8 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 53%.

[0080] The structure and NMR data of the product obtained in Example 13, trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-ene-1-carboxylic acid ethyl ester, are as follows:

[0081]

[0082] trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-ene-1-carboxylic acid ethyl ester1 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.

[0083] Example 14 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-ene-1-carboxylic acid ethyl ester:

[0084] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (92 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 58%.

[0085] The structure and NMR data of the product obtained in Example 14, trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(pyridin-4-yl)cyclobut-2-ene-1-carboxylic acid ethyl ester, are as follows:

[0086]

[0087] trans-2-(1,3-dithian-2-yl)-4-(furan-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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.

[0088] Example 15 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(thiophene-3-yl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0089] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (92 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 57%.

[0090] The structure and NMR data of the product obtained in Example 15, trans-2-(1,3-dithiane-2-yl)-3-phenyl-4-(thiophene-3-yl)cyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0091]

[0092] trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(thiophen-3-yl)cyclobut-2-ene-1-carboxylic acid methyl ester 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.

[0093] Example 16 Preparation of the product trans-4-(benzodioxol-5-yl)-2-(1,3-dithian-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0094] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (120 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 68%.

[0095] The structure and NMR data of the product obtained in Example 16, trans-4-(benzodioxol-5-yl)-2-(1,3-dithian-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester, are as follows:

[0096]

[0097] trans-4-(Benzodioxin-5-yl)-2-(1,3-dithian-2-yl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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.

[0098] Example 17 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid butyl ester:

[0099] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (120 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 73%.

[0100] The structure and NMR data of the product obtained in Example 17, trans-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid butyl ester, are as follows:

[0101]

[0102] Trans-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid butyl ester 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.

[0103] Preparation of the product obtained in Example 18: trans-furan-3-ylmethyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate:

[0104] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (138 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (30 mg, 0.6 mmol) were added and 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 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 obtained by column chromatography with a yield of 52%.

[0105] The structure and NMR data of the product obtained in Example 18, trans-furan-3-ylmethyl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate, are as follows:

[0106]

[0107] trans-Furan-3-ylmethyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate 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.

[0108] Preparation of the product obtained in Example 19: trans-S-ethyl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-thiocarboxylate:

[0109] 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 DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 62%.

[0110] The structure and NMR data of the product obtained in Example 19, trans-S-ethyl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-thiocarboxylate, are as follows:

[0111]

[0112] trans-S-ethyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carbothioate 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.

[0113] Example 20 Preparation of the product trans-(R)-3,7-dimethyloct-6-en-1-yl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate:

[0114] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (172 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 55%.

[0115] The structure and NMR data of the product obtained in Example 20, trans-(R)-3,7-dimethyloct-6-en-1-yl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate, are as follows:

[0116]

[0117] trans-(R)-3,7-dimethyloct-6-en-1-yl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate 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.

[0118] Example 21 Preparation of the product trans-(adamantan-1-yl)methyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate:

[0119] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (178 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 55%.

[0120] The structure and NMR data of the product obtained in Example 21, trans-(adamantan-1-yl)methyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate, are as follows:

[0122]

[0123] trans-(adamantan-1-yl)methyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate 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] Example 22 Preparation of the product trans-2-((1R, 5S)-6,6-dimethylbicyclohept-2-en-2-yl)ethyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate:

[0125] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (178 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 68%.

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

[0127]

[0128] trans-2-((1R,5S)-6,6-dimethylbicyclohept-2-en-2-yl)ethyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate 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] Example 23 Preparation of the product trans-cyclododecyl-2-(1,3-dithiane-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate:

[0130] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (66 mg, 0.3 mmol), the corresponding cinnamate compound (178 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 68%.

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

[0132]

[0133] trans-Cyclododecyl-2-(1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylate 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] Example 24 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3-(2-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0135] In a 25 ml round-bottom flask, 2-((2-methoxyphenyl)ethynyl)-1,3-dithiane (75 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 42%.

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

[0137]

[0138] trans-2-(1,3-dithian-2-yl)-3-(2-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 25 Preparation of the obtained product trans-2-(1,3-dithiane-2-yl)-3-(3-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0140] In a 25 ml round-bottom flask, 2-((3-methoxyphenyl)ethynyl)-1,3-dithiane (75 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 57%.

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

[0142]

[0143] trans-2-(1,3-dithian-2-yl)-3-(3-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 26 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3-(4-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0145] In a 25 ml round-bottom flask, 2-((4-methoxyphenyl)ethynyl)-1,3-dithiane (75 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 60%.

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

[0147]

[0148] trans-2-(1,3-dithian-2-yl)-3-(4-methoxyphenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 27 Preparation of the product trans-3-(4-(tert-butyl)phenyl)-2-(1,3-dithian-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0150] In a 25 ml round-bottom flask, 2-((4-(tert-butyl)phenyl)ethynyl)-1,3-dithiane (83 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and sodium methoxide (4 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 62%.

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

[0152]

[0153] trans-3-(4-(tert-butyl)phenyl)-2-(1,3-dithian-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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 the product obtained in Example 28: trans-2-(1,3-dithiane-2-yl)-3-(4-fluorophenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0155] In a 25 ml round-bottom flask, 2-((4-fluorophenyl)ethynyl)-1,3-dithiane (73 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 63%.

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

[0157]

[0158] trans-2-(1,3-dithian-2-yl)-3-(4-fluorophenyl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 29 Preparation of the product trans-3-(4-chlorophenyl)-2-(1,3-dithian-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid ethyl ester:

[0160] In a 25 ml round-bottom flask, 2-((4-chlorophenyl)ethynyl)-1,3-dithiane (76 mg, 0.3 mmol), the corresponding cinnamate compound (106 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 63%.

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

[0162]

[0163] trans-3-(4-chlorophenyl)-2-(1,3-dithian-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid ethyl ester 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] Example 30 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3-(4-(fluorooxy)phenyl)-4-phenylcyclobut-2-ene-1-carboxylate-difluoro (1 / 1):

[0165] In a 25 ml round-bottom flask, 2-((4-(trifluoromethoxy)phenyl)ethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (106 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 65%.

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

[0167]

[0168] trans-2-(1,3-dithian-2-yl)-4-phenyl-3-(4-(trifluoromethoxy)phenyl)cyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 31 Preparation of the product trans-3-(benzodioxol-5-yl)-2-(1,3-dithian-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0170] In a 25 ml round-bottom flask, 5-((1,3-dithian-2-yl)ethynyl)benzodioxane (78 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 52%.

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

[0172]

[0173] trans-3-(Benzodioxin-5-yl)-2-(1,3-dithian-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 32 Preparation of the product trans-2-(1,3-dithiane-2-yl)-3-(6-methoxynaphthalen-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid ethyl ester:

[0175] In a 25 ml round-bottom flask, 2-((7-methoxynaphthalen-2-yl)ethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium methoxide (4 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 51%.

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

[0177]

[0178] trans-2-(1,3-dithian-2-yl)-3-(6-methoxynaphthalen-2-yl)-4-phenylcyclobut-2-ene-1-carboxylic acid ethyl ester 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). 13C 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] Example 33 Preparation of the resulting product trans-2-(bis(ethylthio)methyl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester:

[0180] In a 25 ml round-bottom flask, (3-phenylprop-2-yn-1,1-diyl)bis(ethylsulfane) (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMF were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium ethoxide (6 mg, 0.06 mmol) were added and 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 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 obtained by column chromatography with a yield of 38%.

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

[0182]

[0183] trans-2-(bis(ethylthio)methyl)-3-phenyl-4-(3,4,5-trimethoxyphenyl)cyclobut-2-ene-1-carboxylic acid ethyl ester 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). 13C 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] Example 34 Preparation of the product trans-2-(2-decyl-1,3-dithiane-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0185] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then iodine nonane (152 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 68%.

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

[0187]

[0188] trans-2-(2-decyl-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1H 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). 13 C 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] Example 35 Preparation of the resulting product trans-2-(2-(oxetane-3-yl)-1,3-dithiane-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0190] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then 3-iodooxetane (110 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 56%.

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

[0192]

[0193] trans-2-(2-(oxetan-3-yl)-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1 H 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] Example 36 Preparation of the product trans-2-(2-benzyl-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0195] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then benzyl bromide (103 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 58%.

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

[0197]

[0198] trans-2-(2-benzyl-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 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). 13C 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] Example 37 Preparation of the product trans-2-(2-(2-methylallyl)-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0200] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then 3-bromo-2-methylpropene (81 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 58%.

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

[0202]

[0203] trans-2-(2-(2-methylallyl)-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1H 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). 13 C 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 the product obtained in Example 38: trans-2-(2-(but-2-yn-1-yl)-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0205] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then 1-bromo-2-butyne (80 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 48%.

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

[0207]

[0208] trans-2-(2-(but-2-yn-1-yl)-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1 H 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] Example 39 Preparation of the product trans-3-phenyl-2-(2-(2-(phenylsulfonyl)ethyl)-1,3-dithian-2-yl)-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0210] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then phenyl vinyl sulfone (100 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 50%.

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

[0212]

[0213] trans-3-phenyl-2-(2-(2-(phenylsulfonyl)ethyl)-1,3-dithian-2-yl)-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 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). 13C 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] Example 40 Preparation of the product trans-2-(2-(4-methoxybenzoyl)-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0215] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then p-methoxybenzoyl chloride (100 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 45%.

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

[0217]

[0218] trans-2-(2-(4-methoxybenzoyl)-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1H 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). 13 C 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] Example 41 Preparation of the product trans-2-(2-(2-chloropyridin-4-yl)-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0220] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then 2-chloro-4-fluoropyridine (79 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 45%.

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

[0222]

[0223] trans-2-(2-(2-chloropyridin-4-yl)-1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 1 H 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] Example 42 Preparation of the product trans-2-(2-cyclopentyl-1,3-dithiane-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0225] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then iodocyclopentane (117 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 57%.

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

[0227]

[0228] trans-2-(2-cyclopentyl-1,3-dithian-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 43 Preparation of the product trans-2-(2-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-1,3-dithian-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0230] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then 5-(2-bromoethyl)-2,3-dihydrobenzofuran (136 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 55%.

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

[0232]

[0233] trans-2-(2-(2-(2,3-dihydrobenzofuran-5-yl)ethyl)-1,3-dithian-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] Example 44 Preparation of the product trans-2-(2-(2-methylpyrimidin-4-yl)-1,3-dithian-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0235] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then 4-fluoro-2-methylpyrimidine (66 mg, 0.6 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 55%.

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

[0237]

[0238] trans-2-(2-(2-methylpyrimidin-4-yl)-1,3-dithian-2-yl)-3-phenyl-4-(p-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 45 Preparation of the product trans-2-(2-(4-nitrophenyl)-1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ethyl ester:

[0240] In a 25 ml round-bottom flask, 2-(phenylethynyl)-1,3-dithiane (90 mg, 0.3 mmol), the corresponding cinnamate compound (97 mg, 0.6 mmol) and 6 ml of DMSO were added in sequence, and then potassium phosphate (13 mg, 0.06 mmol) and potassium tert-butoxide (6 mg, 0.06 mmol) were added and stirred at 50°C for 5 min, and then p-fluoronitrobenzene (126 mg, 0.9 mmol) and potassium tert-butoxide (33 mg, 0.3 mmol) were added and continued to stir for 1 hour. 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 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 obtained by column chromatography with a yield of 58%.

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

[0242]

[0243] trans-2-(2-(4-nitrophenyl)-1,3-dithian-2-yl)-3,4-diphenylcyclobut-2-ene-1-carboxylic acid ethyl ester 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] Example 46 Preparation of the resulting product trans-2-formyl-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester:

[0245] In a 25 ml round-bottom flask, trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester (40 mg, 0.1 mmol), 9 ml of acetonitrile and 1 ml of water were added, and 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 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 (50 ml), dried over anhydrous sodium sulfate, filtered, and the volatiles were removed under vacuum. The product was obtained by column chromatography with a yield of 85%.

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

[0247]

[0248] trans-2-Formyl-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 47 Preparation of the resulting product trans-4-(3-fluorophenyl)-2-methyl-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester:

[0250] In a 25 ml round-bottom flask, add trans-2-(1,3-dithian-2-yl)-4-(3-fluorophenyl)-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester (40 mg, 0.1 mmol) and 8 ml of tetrahydrofuran, then add excess Raney nickel, stir at room temperature for 3 hours, monitor the reaction by thin layer chromatography, filter through a diatomaceous earth pad after the reaction is completed and rinse with ethyl acetate. The filtrate is extracted three times with ethyl acetate (15 ml), the organic phases are combined, the organic phases are washed three times with saturated brine (40 ml), dried over anhydrous sodium sulfate, filtered, and the volatiles are removed under vacuum. The product is obtained by column chromatography with a yield of 89%.

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

[0252]

[0253] trans-4-(3-fluorophenyl)-2-methyl-3-phenylcyclobut-2-ene-1-carboxylic acid methyl ester 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] Example 48 Preparation of the product trans-2-methyl-3-phenyl-4-(o-tolyl)cyclobutane-1-carboxylic acid methyl ester:

[0255] In a 25 ml round-bottom flask, add trans-2-(1,3-dithian-2-yl)-3-phenyl-4-(o-tolyl)cyclobut-2-ene-1-carboxylic acid methyl ester (40 mg, 0.1 mmol) and 8 ml of tetrahydrofuran, then add excess Raney nickel, stir at room temperature for 3 hours under a hydrogen atmosphere, monitor the reaction by thin layer chromatography, filter through a diatomaceous earth pad after the reaction is completed and rinse with ethyl acetate. The filtrate is extracted three times with ethyl acetate (15 ml), the organic phases are combined, the organic phases are washed three times with saturated brine (40 ml), dried over anhydrous sodium sulfate, filtered, and the volatiles are removed under vacuum. The product is obtained by column chromatography with a yield of 85%.

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

[0257]

[0258] trans-2-methyl-3-phenyl-4-(o-tolyl)cyclobutane-1-carboxylic acid methyl ester 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. The present invention relates to a 1,3-dithiane-substituted cyclobutene derivative, characterized in that: The compound has the following general formula (I): In formula (I), R 1 is substituted phenyl (the substituent is selected from one or more of hydrogen, methyl, methoxy, fluorine, chlorine, trifluoromethoxy) or naphthyl; R 2 is substituted phenyl (the substituent is selected from one or more of hydrogen, methyl, methoxy, fluorine, chlorine, bromine, trifluoromethoxy), furyl, thienyl or pyridyl; R 3 is methyl, ethyl, n-butyl, cyclohexyl, benzyl, cyclododecyl, furan derivatives, adamantane derivatives, L-geraniol derivatives, R-(-)-nopol derivatives; 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-chloropyridin-4-yl, 2-methylpyrimidin-4-yl, 4-nitrophenyl; 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 method comprises the following steps: under the action of a strong base, reacting a 2-ethynyl-1,3-dithiane derivative (II), a cinnamate compound (III) and an electrophilic reagent 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 (DMSO), tetrahydrofuran (THF), and N,N-dimethylformamide (DMF); 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, alkyl halide, aryl halide, acyl halide, Michael acceptor and the like.

5. The preparation method according to claim 2, characterized in that: 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).

6. Use of a 1,3-dithiane-substituted cyclobutene derivative according to claim 1 in the synthesis of aldehyde-substituted cyclobutene compounds, characterized in that: The method comprises the following steps: adding a 1,3-dithiane-substituted cyclobutene derivative (I), acetonitrile and water into a reaction container, adding [bis(trifluoroacetoxy)iodo]benzene (PIFA) at 0°C, and reacting at room temperature to obtain the target product IV.

7. Use of a 1,3-dithiane-substituted cyclobutene derivative in the synthesis of a methyl-substituted cyclobutene compound according to claim 1, characterized in that: The method comprises the following steps: adding tetrahydrofuran and a cyclobutene derivative (I) substituted with 1,3-dithiane into a reaction container, adding Raney nickel (Raney-Ni) in batches, and reacting at room temperature to obtain a target product V.

8. The use of a 1,3-dithiane-substituted cyclobutene derivative in the synthesis of a polysubstituted cyclobutane compound according to claim 1, characterized in that: The method comprises the following steps: adding tetrahydrofuran and a cyclobutene derivative (I) substituted with 1,3-dithiane into a reaction container, adding Raney nickel (Raney-Ni) in batches, and reacting at room temperature under a hydrogen atmosphere to obtain a target product VI.

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