Method for synthesizing macrocyclic compound containing conjugated diene structure through intramolecular eneyne coupling and application of macrocyclic compound

Abstract

The invention provides a method for synthesizing a macrocyclic compound containing a conjugated diene structure through intramolecular eneyne coupling and application of the macrocyclic compound, and belongs to the technical field of organic synthesis.The method comprises the steps that a long-carbon-chain acrylamide alkyne compound and a transition metal salt catalyst are placed in an organic solvent; heating and reacting in an inert gas atmosphere to couple eneyne in molecules, and after the reaction is finished, carrying out post-treatment on a reaction solution to obtain a macrocyclic compound containing a conjugated diene structure; according to the method, iridium salt is used for catalyzing intramolecular eneyne coupling to synthesize the macrocyclic compound containing the conjugated diene structure, the synthesis efficiency is high, the method is environmentally friendly, the production environmental protection pressure is small, the method is wide in substrate application range, the method can be used for synthesizing 12-26-membered all-carbon and / or ether macrocyclic compound containing the conjugated diene structure, the atom economy is good, and the method is suitable for industrial production. The reaction yield is high, and the method has a wide application prospect in the field of organic synthesis.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling and its application. Background Art

[0002] The cyclic structure of macrocyclic compounds usually consists of 12 or more carbon atoms. Macrocyclic olefin compounds have a cyclic structure and contain carbon-carbon double bond structures. Due to their unique structures and properties, they show broad application prospects in the fields of organic synthesis, catalysis, materials science, medicinal chemistry, and biology. Researchers have explored various methods for synthesizing macrocyclic compounds, such as olefin metathesis cyclization, macrolactonization reaction, macrocyclic lactamization reaction, etc. According to the functional group-directed strategy, the C-H functionalization reactions of aryl and alkyl groups can be efficiently applied to the synthesis of aryl and alkyl macrocyclic compounds, which not only significantly improves the synthesis efficiency but also exhibits excellent atom economy and step economy, and is expected to play a greater role in the fields of medicinal chemistry, materials science, and supramolecular chemistry.

[0003] The olefin C-H functionalization method has been proven to be an efficient and highly selective method for synthesizing olefin derivatives. However, there are few reports on the synthesis of macrocyclic compounds by the olefin C-H functionalization strategy. The Cossy and Meyer research groups reported a rhodium-catalyzed cyclization reaction of acrylamide to efficiently obtain 12-21 membered macrocyclic compounds containing pyridone (Rhodium(III)-Catalyzed C-H Activation / Heterocyclization as a Macrocyclization Strategy. Synthesis of Macrocyclic Pyridones, Org. Let. 2017, 19, 10, 2706–2709). The patent document with the publication number CN110536748A discloses a method for preparing Z-macrocyclic compounds. This invention uses an easily accessible diene raw material carrying a Z-olefin moiety and a ruthenium-based catalyst supported by a dithiolate ligand to form macrocyclic compounds, and can synthesize macrocyclic lactones with ring sizes in the range of 12-membered rings to 17-membered rings in medium to high yields (68%-79% yield). However, in the prior art, there are no reports on the synthesis of all-carbon macrocyclic olefins and macrocyclic ether olefin compounds using the olefin C-H functionalization strategy. At the same time, the development of a 100% atom-economic synthesis method is also one of the important research directions in the current field of organic synthesis, aiming to maximize the utilization of raw materials, reduce the generation of by-products, and provide an efficient and green route for the synthesis of high-value-added compounds. Summary of the Invention

[0004] The present invention provides a method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling. This method has good atom economy, mild reaction conditions, high synthesis efficiency, and a wide range of substrate applicability.

[0005] The specific technical solution adopted is as follows:

[0006] A method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling, the steps include: placing a long-chain acrylamide alkyne compound and a transition metal salt catalyst in an organic solvent, heating and reacting under an inert gas atmosphere to cause intramolecular enyne coupling. After the reaction is completed, the reaction solution is post-treated to obtain a macrocyclic compound containing a conjugated diene structure shown in Formula I or Formula II;

[0007]

[0008] In Formula I and Formula II, R 1 is p-tolyl, propyl, phenyl or methyl; R 2 is phenyl, substituted phenyl, phenyl-substituted alkyl, thiophenyl or naphthyl;

[0009] In Formula I, both m and n are integers, and 16 ≥ m + n ≥ 2.

[0010] The substituted phenyl can specifically be selected from 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-ethylphenyl, 3-methylphenyl, 2-methoxyphenyl or 2-methylphenyl, etc.

[0011] The phenyl-substituted alkyl can specifically be selected from 3-phenyl-propyl.

[0012] Furthermore, the chemical equation for preparing the macrocyclic compound containing a conjugated diene structure shown in Formula I by the intramolecular enyne coupling reaction of the long-chain acrylamide alkyne compound is expressed as:

[0013]

[0014] The chemical equation for preparing the macrocyclic compound containing a conjugated diene structure shown in Formula II by the intramolecular enyne coupling reaction of the long-chain acrylamide alkyne compound is expressed as:

[0015]

[0016] Preferably, the transition metal salt catalyst is an iridium salt.

[0017] More preferably, the transition metal salt catalyst is dichloro(1,5-cyclooctadiene)iridium(II) dimer.

[0018] The reaction mechanism of the synthesis method of the present invention is as follows: The iridium active intermediate acts on the NH bond of the acrylamide moiety to obtain an amide iridium intermediate. This amide iridium active intermediate undergoes C-H activation with the vinylic C-H bond to produce a five-membered iridium hydride heterocyclic intermediate. Subsequently, the five-membered ring iridium hydride species undergoes an intramolecular cis addition with the alkyne, and finally, reductive elimination and amide ligand exchange occur to generate a macrocyclic compound containing a conjugated diene structure.

[0019] Preferably, the molar ratio of the long-chain acrylamide alkyne compound to the transition metal salt catalyst is 1:0.03 - 0.08, and more preferably 1:0.05.

[0020] Optionally, the organic solvent is methanol, water, ethanol, or ethylene glycol.

[0021] Preferably, the dosage ratio of the organic solvent to the long-chain acrylamide alkyne compound is 50 - 200 L:1 mol, and more preferably 100 L:1 mol.

[0022] Preferably, the inert gas atmosphere is an argon atmosphere, the heating temperature is 60 - 70 °C, and the reaction time is 24 - 72 hours.

[0023] Specifically, the post-treatment method is as follows: The reaction solution is rotary evaporated to dryness under vacuum, loaded onto a column, and the remaining reaction solution is dissolved and transferred with a small amount of dichloromethane, and column chromatography separation is carried out with silica gel. The eluent is a mixed solution of ethyl acetate and petroleum ether with a volume ratio of 1:1.5. The eluate containing the target compound is collected, concentrated, and dried to obtain the corresponding macrocyclic compound containing a conjugated diene structure.

[0024] The present invention also provides the application of the method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling in the field of organic synthesis.

[0025] The present invention also provides a fluorescent material prepared by the method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling.

[0026] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0027] (1) The method of the present invention realizes for the first time the synthesis of a macrocyclic compound containing a conjugated diene structure by iridium salt-catalyzed intramolecular enyne coupling. It has high synthesis efficiency, is environmentally friendly, has little environmental protection pressure in production, and the substrate scope of this method is wide, and it can be used to synthesize all-carbon and / or ether macrocyclic compounds containing conjugated diene structures with 12 - 26 members.

[0028] (2) The synthesis method of the present invention has easily available raw materials, simple steps, mild reaction conditions, high selectivity, good atom economy, high reaction yield, and the highest reaches 79%.

[0029] (3) The method of the present invention is applicable to the efficient chemical modification of bioactive compounds with relatively complex structures, and is an effective supplement to the synthesis and modification methods of natural products and drugs. Description of the Drawings

[0030] Figure 1 It is a characterization diagram of the luminescence performance of the macrocyclic compound containing a conjugated diene structure prepared in Example 7 under ultraviolet light.

[0031] Figure 2 They are the fluorescence performance test results under different environments. Among them, A is the statistical result of the PL intensity, and B is the statistical result of the relative luminescence intensity. Detailed Embodiments

[0032] The present invention will be further illustrated below in conjunction with embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention.

[0033] Example 1

[0034]

[0035] Charge 1,5-cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw-cap vial. Then, add the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat it to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool it, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to separate and obtain a macrocyclic compound containing a conjugated diene structure in the form of a pale yellow liquid (28.8 mg, yield 60%).

[0036] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0037] 1 HNMR(500MHz,Chloroform-d)δ8.16(s,1H),7.71(d,J=8.4Hz,2H),7.36(dd,J=8.2,6.6Hz,2H),7.32–7.27(m,1H),7.14–7.09(m,2H),6.96(d,J=8.1Hz,2H),6.24–6.21(m,1H),6.18(s,1H),2.43–2.37(m,2H),2.34–2.29(m,2H),2.28(s,3H),1.61(dq,J=14.5,7.3Hz,2H),1.51–1.40(m,8H),1.37–1.28(m,8H). 13 CNMR (126 MHz, Chloroform-d) δ 166.34, 144.72, 138.03, 137.95, 136.34, 135.83, 134.89, 130.70, 129.21, 128.73, 128.47, 128.33, 127.38, 33.65, 30.23, 26.93, 26.34, 25.98, 25.68, 25.56, 25.39, 24.57, 24.04, 23.93, 21.61. HRMS (ESI) Calcd for C 29 H 37 NO3S Na [M+Na] + : 502.2386, found: 502.2382. FTIR (KBr, cm -1 ) 3461.50, 2836.26, 2712.91, 1605.61, 1370.09, 1022.43, 781.31.

[0038] Example 2

[0039]

[0040] Charge 1,5-cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw-cap vial. Then, add the long carbon chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to separate a macrocyclic compound containing a conjugated diene structure in the form of a white liquid (28.5 mg, yield 52%).

[0041] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0042] 1 HNMR(500MHz, Chloroform-d) δ 8.08 (s, 1H), 7.81–7.67 (m, 2H), 7.58 (d, J=8.0 Hz, 2H), 7.18 (d, J=8.0 Hz, 2H), 6.99 (d, J=8.1 Hz, 2H), 6.20 (s, 1H), 6.17 (s, 1H), 2.42–2.37 (m, 2H), 2.29–2.23 (m, 5H), 1.58 (p, J=6.7, 6.1 Hz, 3H), 1.48–1.39 (m, 8H), 1.36–1.26 (m, 7H). 13 CNMR (126MHz, Chloroform-d) δ 166.46, 144.93, 140.04, 139.99, 136.71, 136.66, 134.99, 129.24, 128.79 (d, J CF =27.5 Hz), 128.31, 125.15 (q, J CF =4.5, 3.6 Hz), 124.13 (d, J CF =271.6 Hz), 33.62, 30.12, 26.88, 26.14, 25.81, 25.58, 25.50, 25.30, 24.49, 24.03, 23.91, 21.51. 19 FNMR (471MHz, CDCl3) δ -62.50. HRMS (ESI) Calcd for C 30 H 36 F3NO3S Na [M+Na] + : 570.2260, found: 570.2253. FTIR (KBr, cm -1 ) 3446.54, 2836.26, 2707.30, 1591.57, 1364.50, 1081.37, 1025.30, 778.61, 551.54.

[0043] Example 3

[0044]

[0045] A dry screw-cap vial was charged with 1,5-cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) was added to the solution. The vial was sealed under argon and heated to 70 °C and stirred for 36 h for intramolecular enyne coupling. After completion of the reaction, it was cooled, the mixture was filtered and concentrated to give a crude product, which was directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to afford a macrocyclic compound containing a conjugated diene structure as a pale yellow oil (31.1 mg, yield 61%).

[0046] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0047] 1 H NMR (500 MHz, Chloroform-d) δ 8.20 (s, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.6 Hz, 2H), 7.00 (d, J = 8.1 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6.23 (s, 1H), 6.15 (s, 1H), 3.86 (s, 3H), 2.41–2.36 (m, 2H), 2.31 (d, J = 7.3 Hz, 5H), 1.66–1.57 (m, 3H), 1.47 (d, J = 4.5 Hz, 4H), 1.45–1.41 (m, 4H), 1.35–1.27 (m, 7H). 13 C NMR (126 MHz, Chloroform-d) δ 166.36, 158.99, 144.66, 138.56, 136.48, 135.39, 135.02, 130.59, 130.09, 129.21, 128.95, 128.49, 113.78, 55.33, 33.58, 30.27, 26.93, 26.40, 26.04, 25.76, 25.61, 25.43, 24.59, 24.09, 24.00, 21.62. HRMS (ESI) Calcd for C 30 H 39 NO4S Na [M+Na] + : 532.2492, found: 532.2489. FTIR (KBr, cm -1 ) 3461.50, 2833.64, 2729.91, 1600.00, 1364.49, 1207.48, 1084.11, 778.50, 568.22.

[0048] Example 4

[0049]

[0050] Charge a dry screw-cap vial with 1,5-cyclooctadieneiridium(III) dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) andmethanol (10 mL). Then, add the long-chain acrylamide alkyne compound of theabove formula (0.1 mmol, 1.0 equiv) to the solution. Seal the vial underargon and heat to 70 °C and stir for 36 h for intramolecular enyne coupling.After completion of the reaction, cool, filter and concentrate the mixture toobtain a crude product, which is directly used for flash column chromatography(ethyl acetate / petroleum ether mixture) to give a macrocyclic compoundcontaining a conjugated diene structure as a white solid (21.6 mg, 42% yield).

[0051] The characterization data of the macrocyclic compound containing aconjugated diene structure obtained in this example are as follows:

[0052] 1 HNMR (500 MHz, Chloroform-d) δ 8.06 (s, 1H), 7.74 (d, J = 4.6 Hz,2H), 7.30 (d, J = 4.6 Hz, 2H), 7.02 (d, J = 4.4 Hz, 4H), 6.18 (s, 1H), 6.14(s, 1H), 2.40–2.35 (m, 2H), 2.30 (s, 3H), 2.30–2.23 (m, 2H), 1.58 (t, J = 7.6Hz, 3H), 1.44 (dt, J = 18.5, 5.0 Hz, 8H), 1.36–1.23 (m, 7H). 13 C NMR (126 MHz, Chloroform-d) δ 166.42, 144.90, 138.67, 137.27, 136.26,135.03, 134.80, 133.12, 129.98, 129.26, 129.19, 128.47, 128.35, 33.60,30.13, 26.89, 26.21, 25.88, 25.64, 25.53, 25.34, 24.52, 24.04, 23.94,21.61. HRMS (ESI) Calcd for C 29 H 36 ClNO3S Na [M+Na] + : 536.1997, found: 536.1995. FTIR (KBr, cm -1 ) 3461.40, 2839.06, 2721.32, 1599.98, 1361.70, 1072.96, 1019.69,770.20, 559.95.

[0053] Example 5

[0054]

[0055] Charge 1,5 - cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw - cap vial. Then, add the long - carbon - chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to separate a macrocyclic compound with a conjugated diene structure in the form of a white solid (26.9 mg, yield 53%).

[0056] The characterization data of the macrocyclic compound with a conjugated diene structure obtained in this example are as follows:

[0057] 1 H NMR (500 MHz, Chloroform - d) δ8.19 (s, 1H), 7.70 (d, J = 8.3 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.1 Hz, 2H), 6.24–6.22 (m, 1H), 6.16 (s, 1H), 2.69 (q, J = 7.6 Hz, 2H), 2.42–2.36 (m, 2H), 2.35–2.30 (m, 2H), 2.29 (s, 3H), 1.68–1.57 (m, 3H), 1.53–1.40 (m, 8H), 1.35–1.23 (m, 10H). 13 C NMR (126 MHz, Chloroform - d) δ166.39, 144.62, 143.63, 138.32, 137.33, 135.56, 134.93, 133.70, 130.83, 129.18, 128.79, 128.49, 127.83, 33.62, 30.29, 28.67, 26.94, 26.38, 26.02, 25.71, 25.58, 25.41, 24.58, 24.07, 23.96, 21.61, 15.60. HRMS(ESI) Calcd for C 31 H 41 NO3S Na[M + Na] + : 530.2699, found: 530.2704. FTIR (KBr, cm -1)3456.07,2828.04,2718.69,1602.80,1358.88,1106.54,1025.23,772.90,559.81.

[0058] Example 6

[0059]

[0060] Charge 1,5 - cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw - cap vial. Then, add the long - carbon - chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat it to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool it, filter and concentrate the mixture to obtain a crude product, which is directly used for separation by flash column chromatography (ethyl acetate / petroleum ether mixture) to obtain a colorless oily macrocyclic compound containing a conjugated diene structure (27.2 mg, yield 55%).

[0061] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0062] 1 1H NMR (500 MHz, Chloroform - d) δ8.17(s,1H),7.75–7.62(m,2H),7.28–7.23(m,1H),7.12(d,J=7.6Hz,1H),6.99–6.93(m,3H),6.91(s,1H),6.23(s,1H),6.16(s,1H),2.38(s,5H),2.34–2.30(m,2H),2.29(s,3H),1.59(d,J=3.7Hz,4H),1.50–1.40(m,8H),1.36–1.24(m,6H). 13 C NMR (126 MHz, Chloroform - d) δ166.35,144.66,138.13,137.85,137.81,136.27,135.66,134.92,130.97,129.56,129.18,128.49,128.24,128.18,125.75,33.64,30.28,26.90,26.35,26.00,25.70,25.59,25.39,24.56,24.05,23.95,21.58,21.50. HRMS (ESI) Calcd for C 30 H 39 NO3S Na[M+Na]+ : 516.2543, found: 516.2545. FTIR (KBr, cm -1 ) 3498.13, 2828.04, 2727.10, 1602.80, 1375.70, 1064.49, 772.90, 568.22.

[0063] Example 7

[0064]

[0065] Charge a dry screw-cap vial with 1,5-cyclooctadieneiridium(III) dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, add the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equiv) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 h for intramolecular enyne coupling. After completion of the reaction, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to give a macrocyclic compound containing a conjugated diene structure as a white solid (18.0 mg, yield 34%).

[0066] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0067] 1 1H NMR (500 MHz, Chloroform-d) δ 8.16 (s, 1H), 7.88–7.83 (m, 1H), 7.81 (dd, J = 8.9, 5.2 Hz, 2H), 7.69 (d, J = 6.4 Hz, 2H), 7.54–7.47 (m, 3H), 7.23 (dd, J = 8.5, 1.7 Hz, 1H), 6.76 (d, J = 8.1 Hz, 2H), 6.30 (s, 1H), 6.25 (s, 1H), 2.45–2.41 (m, 2H), 2.38 (t, J = 7.7 Hz, 2H), 2.01 (s, 3H), 1.66 (q, J = 7.4 Hz, 2H), 1.53–1.41 (m, 8H), 1.34 (dd, J = 14.7, 5.6 Hz, 8H). 13 C NMR(126 MHz, Chloroform-d) δ 166.59, 144.71, 138.28, 137.65, 136.11, 134.80, 133.83, 133.23, 132.50, 130.61, 129.12, 128.30, 128.09, 127.88, 127.78, 127.61, 126.72, 126.36, 126.24, 33.65, 30.33, 26.94, 26.40, 25.94, 25.72, 25.62, 25.39, 24.57, 24.10, 24.02, 21.26. HRMS(ESI) Calcd for C 33 H 39 NO3S Na [M+Na] + : 552.2543, found: 552.2546. FTIR (KBr, cm -1 ) 3456.07, 2833.64, 2721.50, 1594.39, 1361.68, 1067.29, 1019.63, 775.70, 573.83.

[0068] It was tested that the macrocyclic compound containing a conjugated diene structure has an obvious luminescence phenomenon under ultraviolet light ( Figure 1 ), and it is a fluorescent macrocyclic compound. As shown by A and B in Figure 2 , although it has almost no fluorescence in dimethyl sulfoxide, with the gradual increase of water content, the emission intensity gradually increases. When the water fraction exceeds 80%, due to the restriction of intramolecular rotation, the emission intensity of Example 7 increases significantly. The above results indicate that the macrocyclic compound containing a conjugated diene structure can be used to prepare the luminescent layer material of optoelectronic devices, or for preparing anti-counterfeiting labels, etc.

[0069] Example 8

[0070]

[0071] Charge 1,5-cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw-cap vial. Then, add the long carbon chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool, filter and concentrate the mixture to obtain the crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to separate to obtain a pale yellow oily macrocyclic compound containing a conjugated diene structure (20.4 mg, yield 40%).

[0072] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0073] 1 1H NMR (500 MHz, Chloroform-d) δ 8.43 (s, 1H), 7.72–7.65 (m, 2H), 7.32 (dd, J = 8.7, 7.6, 1.8 Hz, 1H), 7.14 (dd, J = 7.4, 1.6 Hz, 1H), 7.02–6.93 (m, 3H), 6.90 (dd, J = 8.2, 1.0 Hz, 1H), 6.29 (d, J = 1.5 Hz, 1H), 6.22 (s, 1H), 3.80 (s, 3H), 2.43–2.35 (m, 2H), 2.29 (s, 3H), 2.25–2.16 (m, 2H), 1.59 (d, J = 6.3 Hz, 4H), 1.47–1.36 (m, 8H), 1.30 (td, J = 14.7, 6.0, 3.1 Hz, 6H). 13 C NMR (126 MHz, Chloroform-d) δ 166.25, 157.02, 144.41, 138.77, 138.44, 135.42, 135.21, 129.81, 129.08, 129.05, 128.45, 126.68, 125.23, 120.30, 110.27, 55.25, 33.65, 30.88, 26.87, 26.19, 26.09, 25.76, 25.66, 25.41, 24.55, 23.87, 21.59. HRMS (ESI) Calcd for C 30 H 39 NO4S Na [M+H] + : 532.2492, found: 532.2495. FTIR (KBr, cm -1 ) 3481.31, 2833.64, 2721.50, 1608.41, 1367.29, 1070.09, 784.11, 618.69, 557.01.

[0074] Example 9

[0075]

[0076] Into a dry screw-cap vial, 1,5-cyclooctadiene iridium(III) dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) were charged. Then, the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equiv) was added to the solution. The vial was sealed under argon and heated to 90 °C and stirred for 36 h for intramolecular enyne coupling. After completion of the reaction, it was cooled, the mixture was filtered and concentrated to obtain a crude product, which was directly used for separation by flash column chromatography (ethyl acetate / petroleum ether mixture) to give a pale yellow oily macrocyclic compound containing a conjugated diene structure (11.8 mg, yield 24%).

[0077] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0078] 1 HNMR (500 MHz, Chloroform-d) δ 8.20 (s, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.25–7.21 (m, 2H), 7.20–7.13 (m, 2H), 6.95 (d, J = 8.1 Hz, 2H), 6.24 (s, 1H), 6.12 (s, 1H), 2.43–2.37 (m, 2H), 2.28 (s, 3H), 2.24–2.16 (m, 2H), 2.02 (s, 3H), 1.62–1.54 (m, 4H), 1.50–1.40 (m, 9H), 1.36–1.23 (m, 5H). 13 C NMR (126 MHz, Chloroform-d) δ 165.31, 143.65, 136.90, 136.81, 135.76, 134.53, 134.33, 133.81, 128.90, 128.77, 128.08, 127.76, 127.46, 126.71, 124.68, 32.70, 29.40, 25.85, 25.31, 25.03, 24.58, 24.56, 24.31, 23.45, 22.87, 22.81, 20.53, 18.84. HRMS(ESI) Calcd for C 30 H 39 NO3S Na[M+H] + : 516.2543, found: 516.2541. FTIR (KBr, cm -1 ) 3442.06, 2836.45, 2715.89, 1608.41, 1358.88, 1081.31, 1011.21, 778.50, 565.42.

[0079] Example 10

[0080]

[0081] Charge a dry screw-cap vial with iridium(III) dichloride(1,5-cyclooctadiene) dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, add the long carbon chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equiv) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 h for intramolecular enyne coupling. After completion of the reaction, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to give a pale yellow oily macrocyclic compound containing a conjugated diene structure (21.9 mg, 42% yield).

[0082] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0083] 1 HNMR(500MHz,Chloroform-d)δ8.36(s,1H),7.97–7.83(m,2H),7.32–7.25(m,4H),7.22–7.17(m,3H),6.20(s,1H),5.44(t,J=7.3Hz,1H),2.62(t,J=7.6Hz,2H),2.41(s,3H),2.33–2.25(m,2H),2.14–2.04(m,4H),1.72–1.62(m,2H),1.38(dd,J=29.0,12.7,6.6,3.3Hz,11H),1.25(td,J=6.8,3.1Hz,5H),1.20–1.13(m,2H). 13 CNMR (126MHz,Chloroform-d)δ144.86,142.00,138.96,136.37,135.81,133.76,132.49,129.44,128.44,128.43,128.33,125.81,35.56,33.45,30.73,29.39,27.70,26.65,26.25,25.82,25.77,25.68,25.50,24.52,24.20,24.03,21.66. HRMS(ESI) Calcd for C 32 H 43 NO3S Na[M+Na] + :544.2856,found:544.2859. FTIR (KBr,cm -1)3458.88,2833.64,2718.69,1600.00,1356.07,1064.49,1019.63,775.70,557.01.

[0084] Example 11

[0085]

[0086] Charge 1,5 - cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw - cap vial. Then, add the long - carbon - chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat it to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool it, filter and concentrate the mixture to obtain a crude product, which is directly used for separation by flash column chromatography (ethyl acetate / petroleum ether mixture) to obtain a pale - yellow oily macrocyclic compound containing a conjugated diene structure (27.2 mg, yield 56%).

[0087] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0088] 1 HNMR(500MHz,Chloroform - d)δ8.10(s,1H),7.75–7.68(m,2H),7.31(dd,J=5.0,2.9Hz,1H),7.08–7.02(m,3H),6.95(dd,J=5.0,1.2Hz,1H),6.21(s,1H),6.13(s,1H),2.40–2.36(m,4H),2.35(s,3H),1.60(d,J=9.5Hz,4H),1.51–1.39(m,8H),1.37–1.23(m,6H). 13 CNMR (126MHz,Chloroform - d)δ166.46,144.76,137.79,137.42,137.15,135.67,134.98,129.23,128.47,128.32,125.38,124.86,123.93,33.63,30.64,26.89,26.23,25.97,25.85,25.65,25.48,24.65,24.25,24.20,21.68. HRMS(ESI) Calcd for C 27 H 35 NO3S2Na[M+Na] + :508.1951,found:508.1942.FTIR (KBr, cm -1 ) 3447.66, 2830.84, 2718.69, 1602.80, 1356.07, 1213.08, 1075.70, 778.50.

[0089] Example 12

[0090]

[0091] Charge 1,5 - cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw - cap vial. Then, add the long - carbon - chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to separate a macrocyclic compound with a conjugated diene structure in the form of a white solid (19.8 mg, yield 49%).

[0092] The characterization data of the macrocyclic compound with a conjugated diene structure obtained in this example are as follows:

[0093] 1 HNMR (500 MHz, Chloroform - d) δ 7.98 (s, 1H), 7.36 (t, J = 8.2, 6.9 Hz, 2H), 7.29–7.24 (m, 3H), 6.59 (s, 1H), 6.35 (s, 1H), 3.12 (s, 3H), 2.52–2.43 (m, 2H), 2.37 (dd, J = 9.1, 6.4 Hz, 2H), 1.65–1.57 (m, 3H), 1.56–1.50 (m, 2H), 1.49–1.42 (m, 6H), 1.41–1.29 (m, 7H). 13 CNMR (126 MHz, Chloroform - d) δ 138.58, 138.35, 136.20, 135.90, 128.59, 127.58, 41.23, 33.37, 30.14, 26.93, 26.22, 26.02, 25.61, 25.43, 25.37, 24.62, 24.02, 23.86. HRMS(ESI) Calcd for C 23 H 33 NO3SF Na [M + Na] + : 426.2073, found: 426.2080. FTIR (KBr, cm -1)3461.50,2844.86,2704.67,1585.98,1364.49,1028.04,775.70,562.62.

[0094] Example 13

[0095]

[0096] Charge 1,5 - cyclooctadiene iridium(III) dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw - cap vial. Then, add the long - carbon - chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat it to 70 °C and stir for 36 h for intramolecular enyne coupling. After the reaction is completed, cool it, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to separate a macromolecular compound containing a conjugated diene structure as a pale yellow oil (20.0 mg, yield 43%).

[0097] The characterization data of the macromolecular compound containing a conjugated diene structure obtained in this example are as follows:

[0098] 1 HNMR (500 MHz, Chloroform - d) δ 8.22 (s, 1H), 7.84 (dd, 2H), 7.42 (td, J = 7.5 Hz, 1H), 7.40–7.33 (m, 2H), 7.32–7.28 (m, 1H), 7.20 (td, J = 8.5, 7.4 Hz, 2H), 7.14 (dd, J = 7.2, 1.6 Hz, 2H), 6.26 (s, 1H), 6.21 (s, 1H), 2.43–2.36 (m, 2H), 2.33 (t, 2H), 1.69–1.56 (m, 3H), 1.52–1.39 (m, 8H), 1.37–1.19 (m, 7H). 13 C NMR (126 MHz, Chloroform - d) δ 166.24, 138.26, 138.04, 137.88, 136.26, 135.70, 133.69, 130.89, 128.77, 128.57, 128.44, 128.42, 127.48, 33.65, 30.25, 26.90, 26.33, 26.00, 25.69, 25.57, 25.38, 24.55, 24.02, 23.91. HRMS(ESI) Calcd for C 28 H 35 NO3S Na[M + Na] +: 488.2230, found: 488.2224. FTIR (KBr, cm -1 ) 3481.44, 2833.64, 2724.30, 1605.61, 1370.09, 1070.09, 1022.43, 772.90, 571.03.

[0099] Example 14

[0100]

[0101] Charge 1,5 - cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw - cap vial. Then, add the long - carbon - chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for separation by flash column chromatography (ethyl acetate / petroleum ether mixture) to obtain a pale - yellow oily macrocyclic compound containing a conjugated diene structure (16.4 mg, yield 38%).

[0102] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0103] 1 H NMR (500 MHz, Chloroform - d) δ 7.92 (s, 1H), 7.35 (dd, J = 8.2, 6.9 Hz, 2H), 7.29–7.24 (m, 3H), 6.60 (s, 1H), 6.34 (s, 1H), 3.34–3.24 (m, 2H), 2.51–2.43 (m, 2H), 2.38 (t, J = 9.2, 6.4 Hz, 2H), 1.77–1.67 (m, 2H), 1.63–1.57 (m, 2H), 1.52 (td, J = 9.2, 7.7, 4.7 Hz, 2H), 1.50–1.42 (m, 6H), 1.40–1.28 (m, 8H), 0.84 (t, J = 7.4 Hz, 3H). 13 CNMR (126 MHz, Chloroform - d) δ 167.59, 138.52, 138.44, 136.24, 135.70, 130.88, 128.70, 128.49, 127.49, 55.29, 33.53, 30.18, 26.90, 26.21, 26.09, 25.66, 25.49, 25.39, 24.60, 24.02, 23.84, 16.69, 12.55. HRMS(ESI)Calcd for C 25 H 37 NO3S Na[M+Na] + : 454.2386, found: 454.2391. FTIR (KBr, cm -1 ) 3453.27, 2839.25, 2713.08, 1600.00, 1364.49, 1072.90, 1022.43, 778.50, 568.22.

[0104] Example 15

[0105]

[0106] Charge 1,5 - cyclooctadiene iridium(III) dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw - cap vial. Then, add the long - carbon - chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equiv) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 h for intramolecular enyne coupling. After the reaction is completed, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to separate a macrocyclic compound with a conjugated diene structure as a white solid (18.1 mg, yield 40%).

[0107] The characterization data of the macrocyclic compound with a conjugated diene structure obtained in this example are as follows:

[0108] 1 H NMR (500 MHz, Chloroform - d) δ 8.57 (s, 1H), 7.79–7.68 (m, 2H), 7.37 (dd, J = 8.2, 6.7 Hz, 2H), 7.34–7.28 (m, 1H), 7.19 (dd, J = 7.0, 1.7 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 6.52 (d, J = 1.5 Hz, 1H), 6.30 (s, 1H), 2.41 (td, J = 8.9, 3.5 Hz, 4H), 2.33 (s, 3H), 1.68 (td, J = 8.5, 7.6, 5.4 Hz, 2H), 1.51 (td, J = 5.2, 4.3, 2.5 Hz, 3H), 1.46 (q, J = 6.9 Hz, 2H), 1.40 (tt, J = 10.2, 5.5 Hz, 2H), 1.33 (dd, J = 7.8, 4.7 Hz, 2H), 1.28–1.23 (m, 3H). 13 CNMR(126 MHz, Chloroform-d) δ 165.36, 144.76, 140.72, 138.50, 136.09, 135.27, 133.41, 132.34, 129.30, 128.87, 128.48, 128.41, 127.62, 34.58, 29.67, 27.52, 25.93, 25.89, 25.33, 25.25, 25.10, 24.71, 21.64. HRMS(ESI) Calcd for C 27 H 33 NO3S Na [M+Na] + : 474.2073, found: 474.2066. FTIR (KBr, cm -1 ) 3475.42, 2833.45, 2718.52, 1605.59, 1367.31, 1028.10, 778.61, 554.34.

[0109] Example 16

[0110]

[0111] Charge a dry screw-cap vial with 1,5-cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, add the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to separate a macrocyclic compound containing a conjugated diene structure in the form of a white solid (17.8 mg, yield 39%).

[0112] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0113] 1HNMR(500MHz,Chloroform-d)δ10.50(s,1H),7.87(d,J=4.6Hz,2H),7.37(dd,J=8.1,6.6Hz,2H),7.34–7.29(m,1H),7.21(d,J=7.2Hz,2H),7.15(d,J=8.1Hz,2H),6.55(s,1H),6.50(s,1H),4.34–4.30(m,2H),4.17(s,2H),3.67(t,J=4.8Hz,2H),3.43(d,J=4.6Hz,2H),2.36(s,3H),1.66–1.46(m,6H). 13 CNMR (126MHz,Chloroform-d)δ164.90,144.29,138.47,136.06,135.14,134.70,134.51,134.43,129.23,129.17,128.39,128.37,128.04,72.71,69.90,68.91,66.99,27.80,27.32,21.63,20.27. HRMS(ESI) Calcd forC 25 H 29 NO5S Na[M+Na] + :478.1659,found:478.1667. FTIR (KBr,cm -1 )3444.07,2839.25,2713.08,1616.82,1364.49,1215.89,1075.70,781.31,569.70.

[0114] Example 17

[0115]

[0116] A dry screw-cap vial was charged with 1,5-cyclooctadieneiridium(III) dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol(10 mL). Then, the long carbon chain acrylamide alkyne compound of the aboveformula (0.1 mmol, 1.0 equiv) was added to the solution. The vial was sealedunder argon and heated to 70 °C and stirred for 36 h for intramolecularene-yne coupling. After completion of the reaction, the mixture was cooled,filtered and concentrated to give a crude product, which was directly used forseparation by flash column chromatography (ethyl acetate / petroleum ethermixture) to afford a conjugated diene structure-containing macrocycliccompound as a colorless oil (23.2 mg, 47% yield).

[0117] The characterization data of the conjugated diene structure-containingmacrocyclic compound obtained in this example are as follows:

[0118] 1 HNMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.71 (d, J = 6.5 Hz, 2H), 7.34 (dd, J = 8.2, 6.4 Hz, 2H), 7.31–7.27 (m, 1H), 7.09 (d, J = 5.4 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 6.21 (s, 1H), 6.15 (s, 1H), 2.47–2.39 (m, 2H), 2.31 (t, J = 7.5 Hz, 2H), 2.27 (s, 3H), 1.60 (q, J = 7.7 Hz, 3H), 1.53–1.43 (m, 6H), 1.40–1.32 (m, 6H), 1.32–1.22 (m, 5H). 13 CNMR (126 MHz, Chloroform-d) δ 166.69, 144.69, 137.89, 137.77, 136.42, 136.09, 134.72, 131.22, 129.20, 128.84, 128.46, 128.27, 127.37, 34.09, 31.51, 28.19, 27.99, 26.98, 26.78, 26.75, 26.64, 26.46, 26.07, 25.81, 21.61. HRMS(ESI) Calcd for C 30 H 39 NO3S Na [M+Na] + : 516.2543, found: 516.2542. FTIR (KBr, cm -1 ) 3450.47, 2842.06, 2724.30, 1608.41, 1358.88, 1126.17, 1019.63, 784.11, 613.08.

[0119] Example 18

[0120]

[0121] Charge a dry screw-cap vial with 1,5-cyclooctadiene iridium(III) dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, add the long carbon chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equiv) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 h for intramolecular enyne coupling. After completion of the reaction, cool, filter and concentrate the mixture to obtain the crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to give a pale yellow oily macrocyclic compound containing a conjugated diene structure (30.5 mg, 60% yield).

[0122] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0123] 1 HNMR (500 MHz, Chloroform-d) δ 8.06 (s, 1H), 7.71 (d, J = 4.5 Hz, 2H), 7.37–7.32 (m, 2H), 7.31–7.27 (m, 1H), 7.09 (d, J = 6.9 Hz, 2H), 6.94 (d, J = 8.1 Hz, 2H), 6.19 (s, 1H), 6.16 (s, 1H), 2.42–2.38 (m, 2H), 2.33–2.29 (m, 2H), 2.27 (s, 3H), 1.64–1.54 (m, 3H), 1.48–1.38 (m, 7H), 1.36–1.24 (m, 12H). 13 CNMR (126 MHz, Chloroform-d) δ 166.69, 144.70, 137.87, 137.40, 136.42, 136.20, 134.79, 130.86, 129.21, 128.83, 128.46, 128.28, 127.33, 34.50, 31.42, 28.12, 27.58, 27.55, 27.38, 27.18, 26.85, 26.52, 26.33, 25.89, 25.69, 25.33, 21.61. HRMS(ESI) Calcd for C 31 H 41 NO3S Na [M+Na] + : 530.2699, found: 530.2699. FTIR (KBr, cm -1 ) 3489.72, 2833.64, 2718.69, 1594.39, 1361.68, 1078.50, 1014.02, 775.70, 565.42.

[0124] Example 19

[0125]

[0126] Charge a dry screw-cap vial with iridium(III) chloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, add the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equiv) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 h for intramolecular enyne coupling. After completion of the reaction, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to give a pale yellow oily macrocyclic compound containing a conjugated diene structure (35.4 mg, 66% yield).

[0127] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0128] 1 HNMR (500 MHz, Chloroform-d) δ 8.06 (s, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.34 (t, J = 7.4 Hz, 2H), 7.31–7.27 (m, 1H), 7.08 (d, J = 8.7 Hz, 2H), 6.92 (d, J = 8.1 Hz, 2H), 6.20 (s, 1H), 6.15 (s, 1H), 2.39 (t, J = 6.4 Hz, 2H), 2.34–2.27 (m, 2H), 2.27 (s, 3H), 1.56 (q, J = 7.6 Hz, 2H), 1.48–1.39 (m, 7H), 1.36–1.28 (m, 15H). 13 CNMR (126 MHz, Chloroform-d) δ 166.84, 144.69, 137.97, 137.33, 136.42, 136.28, 134.73, 131.11, 129.21, 128.84, 128.46, 128.28, 127.34, 34.74, 31.87, 28.66, 28.29, 28.00, 27.97, 27.43, 27.35, 27.28, 27.03, 26.85, 26.83, 26.66, 21.61. HRMS(ESI) Calcd for C 32 H 43 NO3S Na [M+Na] + : 544.2856, found: 544.2853. FTIR (KBr, cm -1)3461.68,2833.64,2718.69,1614.02,1367.29,1064.49,1025.23,778.50,573.83.

[0129] Example 20

[0130]

[0131] Charge 1,5 - cyclooctadieneiridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into an oven - dried screw - cap vial. Then, add the long - chain acrylamide alkyne compound (0.1 mmol, 1.0 equiv) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 h. After cooling, filter and concentrate the mixture to obtain the crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to give a pale yellow oil (38.6 mg, yield 70%).

[0132] The peaks in the NMR spectrum are assigned as follows: 1 HNMR (500 MHz, CDCl3) δ 9.10 (s, 1H), 7.76 (d, J = 6.5 Hz, 2H), 7.34–7.21 (m, 3H), 7.05 (d, J = 7.1 Hz, 2H), 6.91 (d, J = 8.1 Hz, 2H), 6.20 (s, 1H), 6.05 (s, 1H), 3.50 (q, J = 5.3 Hz, 4H), 2.33 (td, J = 7.2, 1.7 Hz, 4H), 2.23 (s, 3H), 1.76–1.62 (m, 4H), 1.60 (t, J = 6.8 Hz, 3H), 1.48–1.39 (m, 2H), 1.38–1.34 (m, 6H), 1.33–1.28 (m, 7H). 13 CNMR (126 MHz, CDCl3) δ 168.13, 144.44, 137.64, 137.12, 136.68, 135.09, 134.79, 130.97, 129.15, 128.89, 128.40, 128.10, 127.00, 71.14, 69.84, 35.35, 31.01, 29.40, 29.21, 27.91, 27.75, 27.65, 27.38, 27.21, 27.07, 27.01, 25.32, 25.05, 21.59. HRMS(ESI) Calcd forC 33 H 45 NO4S Na[M+Na] + :574.2962,found:574.2961. FTIR (KBr,cm-1 )3447.66,2825.23,2721.50,1611.21,1370.09,1084.11,1022.43,778.50,601.87.

[0133] Example 21

[0134]

[0135] Charge 1,5 - cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw - cap vial. Then, add the long - carbon - chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 h for intramolecular enyne coupling. After the reaction is completed, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for separation by flash column chromatography (ethyl acetate / petroleum ether mixture) to obtain a pale - yellow oily macrocyclic compound containing a conjugated diene structure (44.5 mg, yield 75%).

[0136] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0137] 1 HNMR(500MHz,CDCl3)δ8.07(s,1H),7.72(d,J = 8.3Hz,2H),7.38–7.30(m,2H),7.31–7.28(m,1H),7.07(d,J = 3.1Hz,2H),6.93(d,J = 8.1Hz,2H),6.19(s,1H),6.15(s,1H),3.44(td,J = 6.0,2.7Hz,4H),2.38–2.29(m,4H),2.27(s,3H),1.63–1.49(m,7H),1.46–1.36(m,11H),1.33–1.28(m,10H). 13 C NMR (126MHz,CDCl3)δ166.89,144.69,137.86,136.74,136.42,136.23,134.76,130.89,129.21,128.86,128.46,128.26,127.30,69.93,34.50,31.73,29.78,29.42,29.35,29.06–28.91(m),28.81,28.61,28.55,27.95,27.84,26.96,25.94,25.60,21.61. HRMS(ESI) Calcd for C 36 H51 NO4S Na[M+Na] + : 616.3431, found: 616.3434. FTIR (KBr, cm -1 ) 3450.47, 2828.04, 2727.10, 1588.79, 1364.49, 1072.90, 1022.43, 772.90, 551.40.

[0138] Example 22

[0139]

[0140] Charge 1,5 - cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL) into a dry screw - cap vial. Then, add the long - carbon - chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 hours for intramolecular enyne coupling. After the reaction is completed, cool, filter and concentrate the mixture to obtain a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to obtain a pale - yellow oily macrocyclic compound containing a conjugated diene structure (45.5 mg, yield 70%).

[0141] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0142] 1 HNMR (500 MHz, Chloroform - d) δ 8.03 (s, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 7.5 Hz, 2H), 7.29 (d, J = 7.4 Hz, 1H), 7.08 (d, J = 7.5 Hz, 2H), 6.93 (d, J = 8.2 Hz, 2H), 6.19 (s, 1H), 6.15 (s, 1H), 3.42 (t, J = 5.7 Hz, 4H), 2.33 (dt, J = 19.5, 7.6 Hz, 4H), 2.27 (s, 3H), 1.60–1.51 (m, 10H), 1.40 (dt, J = 21.6, 7.3 Hz, 8H), 1.35–1.27 (m, 18H). 13 C NMR(126MHz, Chloroform-d) δ 166.85, 144.67, 137.96, 136.76, 136.50, 136.42, 134.78, 130.80, 129.20, 128.84, 128.47, 128.26, 127.30, 70.23, 70.16, 34.68, 31.70, 29.78, 29.69, 29.67, 29.61, 29.54, 29.52, 29.49, 29.47, 29.38, 29.29, 29.28, 29.08, 29.03, 28.54, 27.48, 26.46, 26.20, 21.60, 14.12. HRMS(ESI) Calcd for C 40 H 59 NO4S Na [M+Na] + : 672.4057, found: 672.4061. FTIR (KBr, cm -1 ) 3436.52, 2830.85, 2718.71, 1591.61, 1361.71, 1070.12, 772.93.

[0143] Example 23

[0144]

[0145] Charge an oven-dried screw-cap vial with 1,5-cyclooctadieneiridium(III) dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, add a long-chain acrylamide alkyne compound (0.1 mmol, 1.0 equiv) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 h. After cooling, filter and concentrate the mixture to give a crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to give a pale yellow oil (35.9 mg, 65% yield).

[0146] The peaks of the NMR spectrum are assigned as follows: 1 HNMR (500 MHz, CDCl3) δ 8.04 (s, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.1 Hz, 2H), 6.88 (d, J = 8.7 Hz, 2H), 6.21 (s, 1H), 6.12 (s, 1H), 3.86 (s, 3H), 2.39–2.35 (m, 2H), 2.30 (t, J = 6.9 Hz, 5H), 1.57 (d, J = 10.9 Hz, 2H), 1.44 (m, 8H), 1.32 (m, 14H). 13 CNMR(126 MHz, Chloroform-d) δ 166.82, 158.98, 144.61, 138.04, 136.32, 135.79, 134.91, 131.04, 130.22, 129.20, 129.07, 128.49, 113.73, 55.33, 34.68, 31.90, 29.70, 28.71, 28.34, 28.28, 28.00, 27.43, 27.35, 27.27, 27.05, 26.89, 26.84, 26.63, 21.60. HRMS(ESI) Calcd for C 33 H 45 NO4S Na [M+Na] + : 574.2962, found: 574.2957. FTIR (KBr, cm -1 ) 3453.27, 2830.84, 2710.28, 1583.18, 1364.49, 1103.74, 1028.04, 770.09.

[0147] Example 24

[0148]

[0149] A dry screw-cap vial was charged with 1,5-cyclooctadiene iridium dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equivalent) was added to the solution. The vial was sealed under argon and heated to 70 °C and stirred for 36 h for intramolecular enyne coupling. After completion of the reaction, it was cooled, the mixture was filtered and concentrated to obtain a crude product, which was directly used for separation by flash column chromatography (ethyl acetate / petroleum ether mixture) to obtain a pale yellow oily macrocyclic compound containing a conjugated diene structure (42.3 mg, yield 79%).

[0150] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0151] 1HNMR(500MHz,Chloroform-d)δ8.07(s,1H),7.72(d,J=8.3Hz,2H),7.27–7.24(m,1H),7.11(d,J=7.6Hz,1H),6.93(d,J=8.3Hz,3H),6.89(s,1H),6.20(s,1H),6.13(s,1H),2.38(t,J=6.2Hz,5H),2.31(t,2H),2.27(s,3H),1.57(t,J=7.8Hz,4H),1.49–1.36(m,9H),1.33(q,J=6.2Hz,11H). 13 CNMR (126MHz,Chloroform-d)δ166.81,144.60,137.79,137.76,137.50,136.36,136.14,134.80,131.33,129.72,129.17,128.49,128.18,128.13,125.85,34.73,31.90,29.71,28.67,28.28,28.01,27.98,27.43,27.35,27.28,27.03,26.86,26.67,21.56,21.50,14.13. HRMS(ESI) Calcd for C 33 H 45 NO3S Na[M+Na] + :558.3012,found:558.3017. FTIR (KBr,cm -1 )3447.66,2828.04,2721.50,1605.61,1367.29,1218.69,1072.90,778.50.

[0152] Example 25

[0153]

[0154] A dry screw-cap vial was charged with 1,5-cyclooctadieneiridium(III) dichloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol(10 mL). Then, the long-chain acrylamide alkyne compound of the above formula(0.1 mmol, 1.0 equiv) was added to the solution. The vial was sealed underargon and heated to 70 °C and stirred for 36 h for intramolecular enynecoupling. After completion of the reaction, the mixture was cooled, filteredand concentrated to give a crude product, which was directly used for flashcolumn chromatography (ethyl acetate / petroleum ether mixture) to afford amacrocyclic compound containing a conjugated diene structure as a pale yellowoil (30.0 mg, 53% yield).

[0155] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0156] 1 HNMR (500 MHz, Chloroform-d) δ 8.11 (s, 1H), 7.92 (d, J = 8.3 Hz, 2H), 7.31–7.26 (m, 4H), 7.21–7.16 (m, 3H), 6.15 (s, 1H), 5.42 (t, J = 7.3 Hz, 1H), 2.60 (t, J = 7.6 Hz, 2H), 2.40 (s, 3H), 2.27 (t, J = 6.3 Hz, 2H), 2.05 (dt, J = 18.8, 7.0 Hz, 4H), 1.65 (q, J = 7.7 Hz, 4H), 1.40–1.32 (m, 9H), 1.32–1.26 (m, 13H). 13 CNMR (126 MHz, Chloroform-d) δ 166.56, 144.86, 142.02, 138.08, 136.18, 135.83, 134.31, 133.08, 129.46, 128.44, 128.43, 128.31, 125.78, 35.54, 34.46, 30.91, 30.63, 29.71, 28.28, 28.09, 28.05, 27.93, 27.81, 27.40, 27.21, 27.13, 27.09, 27.04, 26.91, 26.63, 21.65. HRMS(ESI) Calcd for C 35 H 49 NO3S Na [M+Na] + : 586.3325, found: 586.3324. FTIR (KBr, cm -1 ) 3400.00, 2828.04, 2713.08, 1608.41, 1358.88, 1070.09, 770.09.

[0157] Example 26

[0158]

[0159] An oven-dried screw-cap vial was charged with 1,5-cyclooctadieneiridium(III) chloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equiv) was added to the solution. The vial was sealed under argon and heated to 70 °C and stirred for 36 h for intramolecular enyne coupling. After the reaction was completed, it was cooled, the mixture was filtered and concentrated to give a crude product, which was directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to give a macrocyclic compound containing a conjugated diene structure as a pale yellow oil (35.9 mg, yield 68%).

[0160] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0161] 1 HNMR (500 MHz, Chloroform-d) δ 7.97 (s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.30 (dd, J = 5.0, 2.9 Hz, 1H), 7.03 (d, J = 4.8 Hz, 3H), 6.91 (d, J = 4.8 Hz, 1H), 6.19 (s, 1H), 6.11 (s, 1H), 2.39–2.35 (m, 4H), 2.34 (s, 3H), 1.62–1.54 (m, 5H), 1.49–1.41 (m, 9H), 1.36–1.28 (m, 10H). 13 CNMR (126 MHz, Chloroform-d) δ 166.91, 144.72, 137.57, 137.30, 136.98, 136.04, 134.86, 129.22, 128.47, 128.42, 125.23, 125.21, 124.05, 34.72, 32.22, 29.71, 28.35, 28.26, 27.96, 27.40, 27.36, 27.22, 27.05, 26.85, 26.81, 26.62, 21.68, 14.13. HRMS(ESI) Calcd for C 30 H 41 NO3S2 Na [M+Na] + : 550.2420, found: 550.2424. FTIR (KBr, cm -1 ) 3392.17, 2828.04, 2718.69, 1611.21, 1361.68, 1078.50, 770.09.

[0162] Example 27

[0163]

[0164] Charge a dry screw-cap vial with iridium(III) chloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, add the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equiv) to the solution. Seal the vial under argon and heat to 70 °C and stir for 36 h for intramolecular alkyne-ene coupling. After completion of the reaction, cool the mixture, filter and concentrate to obtain the crude product, which is directly used for flash column chromatography (ethyl acetate / petroleum ether mixture) to afford the macrocyclic compound containing conjugated diene structure as a pale yellow oil (27.6 mg, 62% yield).

[0165] The characterization data of the macrocyclic compound containing conjugated diene structure obtained in this example are as follows:

[0166] 1 HNMR (500 MHz, Chloroform-d) δ 7.85 (s, 1H), 7.36 (t, J = 7.5 Hz, 2H), 7.30–7.24 (m, 3H), 6.58 (s, 1H), 6.34 (s, 1H), 3.10 (s, 3H), 2.46 (t, J = 7.1 Hz, 2H), 2.37 (t, 2H), 1.59–1.48 (m, 6H), 1.46–1.32 (m, 18H). 13 CNMR (126 MHz, Chloroform-d) δ 168.11, 138.53, 137.87, 136.44, 136.24, 131.29, 128.70, 128.60, 127.64, 41.14, 34.35, 31.80, 28.52, 28.31, 28.27, 28.01, 27.88, 27.47, 27.35, 27.28, 26.97, 26.91, 26.87, 26.73. HRMS(ESI) Calcd for C 26 H 39 NO3S Na [M+Na] + : 468.2543, found: 468.2550. FTIR (KBr, cm -1 ) 3453.27, 2839.25, 2715.89, 1591.59, 1361.68, 1204.67, 1075.70, 775.70.

[0167] Example 28

[0168]

[0169] A dry screw-cap vial was charged with 1,5-cyclooctadiene iridium(III) chloride dimer (3.4 mg, 5 mol%, 0.005 mmol) and methanol (10 mL). Then, the long-chain acrylamide alkyne compound of the above formula (0.1 mmol, 1.0 equiv) was added to the solution. The vial was sealed under argon and heated to 70 °C and stirred for 36 h for intramolecular enyne coupling. After completion of the reaction, the mixture was cooled, filtered and concentrated to give a crude product, which was directly used for separation by flash column chromatography (ethyl acetate / petroleum ether mixture) to obtain a pale yellow oily macrocyclic compound containing a conjugated diene structure (27.8 mg, yield 43%).

[0170] The characterization data of the macrocyclic compound containing a conjugated diene structure obtained in this example are as follows:

[0171] 1 HNMR (500 MHz, Chloroform-d) δ 8.18 (s, 1H), 7.72 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H), 7.11 (d, J = 7.9 Hz, 2H), 6.99 (d, J = 8.1 Hz, 2H), 6.23 (s, 1H), 6.21 (s, 1H), 5.42 (t, 1H), 5.12 (t, 1H), 4.53 (s, 2H), 4.09 (d, J = 6.8 Hz, 2H), 2.42–2.37 (m, 2H), 2.34–2.28 (m, 5H), 2.12 (dd, J = 8.8, 6.3 Hz, 2H), 2.07 (d, J = 8.5 Hz, 2H), 1.71–1.64 (m, 6H), 1.63–1.57 (m, 3H), 1.48–1.40 (m, 10H), 1.36–1.27 (m, 8H). 13 CNMR (126 MHz, Chloroform-d) δ 166.27, 144.74, 140.56, 138.08, 138.03, 137.96, 135.71, 135.59, 134.99, 131.69, 130.64, 129.23, 128.74, 128.48, 127.79, 123.96, 120.74, 71.66, 66.84, 39.62, 33.63, 30.27, 26.91, 26.39, 26.32, 26.02, 25.71, 25.58, 25.41, 24.57, 24.06, 23.95, 21.59, 17.70, 16.56, 14.13. HRMS (ESI) Calcd for C 40 H 55 NO4S Na [M+Na] +: 688.3744, found: 688.3740. FTIR (KBr, cm -1 ) 3454.78, 2828.04, 2715.89, 1591.59, 1361.68, 1072.90, 770.09.

[0172] Application Example 1

[0173]

[0174] Weigh Pd / C (20 wt%) and the macrocyclic compound containing conjugated diene structure prepared in Example 1 (0.1 mmol, 1.0 equiv)) and dissolve them in 1.0 mL of methanol solution. Insert a hydrogen balloon, evacuate and refill the gas 5 - 6 times, and react for 4 h in a hydrogen atmosphere. After the reaction, transfer the reaction solution to a 25 mL round-bottom flask and rotary evaporate the solvent under vacuum. The obtained crude product is purified by silica gel column chromatography to obtain a macrocyclic compound with both double bonds reduced (336.3 mg, yield 75%).

[0175] The characterization data of the product are as follows:

[0176] 1 HNMR (500 MHz, CDCl3) δ 8.75 (s, 1H), 7.91 (dd, J = 8.5, 1.8 Hz, 2H), 7.33–7.27 (m, 3H), 7.22 (dd, J = 8.2, 6.9 Hz, 1H), 7.17–7.09 (m, 1H), 7.03–6.97 (m, 2H), 2.60 (dd, J = 13.6, 5.3 Hz, 1H), 2.44 (d, J = 5.3 Hz, 1H), 2.38 (s, 2H), 2.32 (td, J = 10.0, 5.1 Hz, 1H), 2.11 (dd, J = 13.6, 8.3 Hz, 1H), 1.65 (ddt, J = 13.7, 9.1, 4.4 Hz, 1H), 1.50–1.39 (m, 5H), 1.37–1.21 (m, 16H). 13 C NMR (126 MHz, Chloroform-d) δ 174.25, 145.09, 140.50, 135.36, 129.54, 129.10, 128.33, 128.18, 125.80, 46.25, 42.40, 40.57, 36.18, 35.65, 28.83, 27.10, 26.21, 25.58, 25.20, 24.90, 24.50, 24.14, 24.06, 23.48, 21.64. HRMS(ESI) Calcd for C 29 H 41NO3S Na[M+Na] + : 506.2699, found: 506.2699.

[0177] Application Example 2

[0178]

[0179] Potassium carbonate (83.0 mg, 0.6 mmol) and methyl iodide (85.2 mg, 0.6 mmol) were added to a 25 mL round-bottom flask, 3 mL of N,N-dimethylformamide (DMF) was added and mixed, and then the macrocyclic compound containing a conjugated diene structure prepared in Example 1 (0.3 mmol) was added. The flask was sealed with argon and stirred at 40 °C for 3 hours. Thin layer chromatography showed that the raw materials had completely reacted, and the reaction was stopped. It was extracted with ten times the volume of water and ethyl acetate, and the solvent ethyl acetate was evaporated to dryness under vacuum. The obtained crude product was purified by silica gel column chromatography to obtain the intermediate product in a yield of 98%. The obtained intermediate product was added to a 15 mL round-bottom pressure-resistant sealed tube, NaOH (6 M, 4.0 mL) was added, and the temperature was raised to 120 °C and stirred in an argon atmosphere for 16 hours. Thin layer chromatography showed that the raw materials had completely reacted, and the reaction was stopped. It was diluted with water, acidified with 3 M HCl, extracted with ethyl acetate, dried over anhydrous Na2SO4, filtered, and the solvent ethyl acetate was evaporated to dryness under vacuum. The obtained crude product was purified by silica gel column chromatography to obtain the product carboxylic acid (42.7 mg, yield 89%).

[0180] Step 1 The characterization data of the intermediate product are as follows:

[0181] 1 1H NMR (500 MHz, Chloroform-d) δ 7.73 (d, J = 8.4 Hz, 2H), 7.30–7.25 (m, 2H), 7.23 (d, J = 7.2 Hz, 1H), 6.92 (t, J = 7.6 Hz, 4H), 5.99 (s, 1H), 5.95 (s, 1H), 3.40 (s, 3H), 2.40–2.31 (m, 2H), 2.22 (s, 3H), 2.17 (t, J = 7.5 Hz, 2H), 1.50 (dt, J = 15.1, 6.5 Hz, 4H), 1.44–1.28 (m, 14H). 13 CNMR (126 MHz, Chloroform-d) δ 170.77, 144.36, 138.75, 137.10, 135.52, 135.36, 133.33, 129.15, 128.74, 128.24, 127.97, 126.66, 33.95, 33.62, 30.24, 26.91, 25.93, 25.88, 25.75, 25.53, 25.36, 24.46, 24.10, 21.61.HRMS(ESI) Calculated for C 30 H 39 NO3S Na[M+Na] + : 516.2543, found: 516.2547.

[0182] The characterization data of the final product in Step 2 are as follows:

[0183] 1 HNMR(500 MHz, Chloroform-d) δ 9.40 (s, 1H), 7.34–7.28 (m, 2H), 7.22 (dd, J=7.8, 5.9 Hz, 3H), 6.45 (s, 1H), 6.28 (s, 1H), 2.45–2.38 (m, 2H), 2.33 (t, J=7.5 Hz, 2H), 1.56 (t, J=7.5 Hz, 2H), 1.47 (td, J=8.9, 7.6, 4.5 Hz, 2H), 1.41 (d, J=7.4 Hz, 6H), 1.37–1.26 (m, 8H). 13 CNMR (126 MHz, CDCl3) δ 174.91, 140.05, 139.82, 137.62, 133.16, 128.74, 128.10, 128.03, 126.59, 33.77, 30.08, 26.77, 26.24, 26.19, 25.82, 25.79, 25.45, 24.41, 24.08, 23.99.

[0184] Application Example 3

[0185]

[0186] Weigh (33.0 mg, 0.1 mmol) of the acid synthesized in Application Example 2, PPDF (26 mg, 0.16 mmol), and Tf-PPDF (76.0 mg, 2.0 mmol) into a 10 mL round-bottom flask, add 0.5 mL of dichloromethane solution and mix. Then weigh (14.0 mg, 0.11 mmol) of pinacol borane (HBpin) into the mixture, seal it with argon gas, and stir at room temperature for 10 minutes. Thin-layer chromatography shows that the raw materials have completely reacted, and the reaction is stopped. Dilute it with water to quench, extract with dichloromethane, dry over anhydrous Na2SO4, filter, and rotary evaporate the dichloromethane solvent under vacuum. The obtained crude product is purified by silica gel column chromatography to obtain the product aldehyde (24.8 mg, yield 79%).

[0187] The characterization data of the product are as follows:

[0188] 1HNMR(500MHz,CDCl3)δ8.00(s,1H),7.38–7.28(m,2H),7.27–7.22(m,1H),7.16–7.08(m,2H),5.33(t,J=9.3,7.7Hz,1H),4.03(s,1H),2.53–2.39(m,3H),2.38–2.20(m,1H),1.80–1.71(m,1H),1.66(m,1H),1.52(td,J=8.3,4.9,2.9Hz,2H),1.42(dd,J=8.7,3.6Hz,3H),1.34–1.24(m,7H),1.17(dt,J=9.4,6.5,4.0Hz,4H). 13 CNMR (126MHz,CDCl3)δ206.11,151.94,143.58,141.06,138.10,128.65,128.63,128.03,126.89,56.83,29.71,27.16,26.90,26.59,26.15,25.50,24.56,24.47,24.26,23.70. HRMS(ESI) Calcd forC 22 H 30 O H[M-H] - :309.2224,found:309.2224.

[0189] The embodiments described above have elaborated on the technical solutions of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not used to limit the present invention. Any modifications, supplements, or substitutions in a similar manner made within the scope of the principles of the present invention shall be included within the protection scope of the present invention.

[0190] Application Example 4

[0191]

[0192] The macrocyclic compound containing a conjugated diene structure synthesized in Example 16 (45.5 mg, 0.1 mmol), CuI (1.9 mg, 0.01 mmol), TMEDA (5.8 mg, 0.05 mmol), and K2CO3 (13.8 mg, 0.1 mmol) were placed in a 10 mL round-bottom flask, 1 mL of THF solution was added and mixed, sealed with oxygen, and stirred overnight at 80 °C. Thin-layer chromatography showed that the raw materials had completely reacted, and the reaction was stopped. Diluted with water to quench, extracted with dichloromethane, dried over anhydrous Na2SO4, filtered, and the solvent was rotary evaporated in vacuo. The obtained crude product was dissolved in 0.01 M sodium hydroxide methanol solution and stirred overnight at room temperature. Diluted with ten times the amount of water to quench, extracted with dichloromethane, dried over anhydrous Na2SO4, filtered, and after vacuum concentration, the crude product was purified by silica gel column chromatography to obtain macrocyclic pyridine amide (20.6 mg, yield 69%). This product was reported in the paper Org. Lett. 2017, 19, 2706 (Rhodium(III)-Catalyzed C-H Activation / Heterocyclization as a Macrocyclization Strategy. Synthesis of Macrocyclic Pyridones).

[0193] The characterization data of the product macrocyclic pyridine amide are as follows:

[0194] 1 HNMR (500 MHz, CDCl3) δ 11.62 (s, 1H), 8.20 (s, 1H), 7.47–7.43 (m, 3H), 7.40–7.35 (m, 2H), 4.56 (brs, 2H), 4.43 (brs, 2H), 3.62 - 3.65 (m, 2H), 3.13 - 3.17 (m, 2H), 1.84 - 1.76 (m, 2H), 1.46 - 1.34 (brm, 2H), 1.34–1.23 (brm, 2H). 13 CNMR (126 MHz, CDCl3) δ 162.1, 142.6, 138.1, 132.5, 130.5, 129.7, 129.2, 128.7, 115.4, 72.9, 68.6, 67.2, 65.5, 28.2, 28.0, 20.6. HRMS(ESI) Calcd for C 18 H 21 NO3Na [M+Na] + : 322.1444, found: 322.1448.

[0195] The embodiments described above have elaborated on the technical solutions of the present invention. The above are only specific embodiments of the present invention and are not used to limit the present invention. Any modifications, supplements, etc. made within the principle scope of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling, characterized in that the steps Comprising: Placing a long-chain acrylamide alkyne compound and a transition metal salt catalyst in an organic solvent, heating and reacting under an inert gas atmosphere to cause intramolecular enyne coupling, and after the reaction is completed, the reaction solution is post-treated to obtain a macrocyclic compound containing a conjugated diene structure shown in Formula I or Formula II; In Formula I and Formula II, R 1 is p-methylphenyl, propyl, phenyl or methyl; R 2 is phenyl, substituted phenyl, phenyl-substituted alkyl, thienyl or naphthyl; In Formula I, both m and n are integers, and 16 ≥ m + n ≥ 2.

2. The method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling according to claim 1, wherein The substituted phenyl group is selected from 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-ethylphenyl, 3-methylphenyl, 2-methoxyphenyl or 2-methylphenyl; the alkyl group substituted by phenyl is selected from 3-phenyl-propyl.

3. The method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling according to claim 1, wherein The transition metal salt catalyst is an iridium salt.

4. The method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling according to claim 3, characterized in that, The transition metal salt catalyst is 1,5-cyclooctadiene iridium dichloride dimer.

5. The method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling according to claim 1, characterized in that, The molar ratio of the long-chain acrylamide alkyne compound to the transition metal salt catalyst is 1:0.03 - 0.

08.

6. The method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling according to claim 1, wherein The organic solvent is methanol, water, ethanol or ethylene glycol.

7. The method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling according to claim 1, wherein The dosage ratio of the organic solvent to the long-chain acrylamide alkyne compound is 50 - 200 L:1 mol.

8. The method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling according to claim 1, characterized in that, The inert gas atmosphere is an argon atmosphere, the heating temperature is 60 - 70 °C, and the reaction time is 24 - 72 hours.

9. Use of the method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling according to any one of claims 1 - 8 in the field of organic synthesis.

10. A fluorescent material, characterized in that, Prepared by the method for synthesizing a macrocyclic compound containing a conjugated diene structure by intramolecular enyne coupling according to any one of claims 1 - 8.

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