Method for preparing a bromochloride or bromoazide

Abstract

The present invention discloses a preparation method of bromochlorides or bromoazides. Using 1,3-conjugated diene compounds as raw materials and NBS as the bromine positive reagent, they are respectively combined with TMSCl or TMSN 3 to achieve the selective bromochlorination and bromoazidation reactions of 1,3-conjugated dienes, and a series of bromochlorides and bromoazides with wide applications are successfully obtained. The present invention adopts a one-step method with mild conditions, without any metals and additives, simple operation, high reaction efficiency, wide substrate scope, and high yields, regioselectivities and stereoselectivities of the products. The present invention provides a new means for synthesizing various bromochlorides and bromoazides, with strong economic practicability and industrial application prospects. In addition, a series of derivatization reactions indicate that the above products have important synthetic application values.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation of organic halides in the direction of organic synthesis, and specifically relates to a method for preparing bromochlorides or bromoazides. Background Art

[0002] Organic halides are a class of important compounds, widely present in pesticides, drugs and natural products, and play important roles in human production and life. So far, more than 5,000 naturally occurring organic halides have been isolated and characterized, such as: terpene compounds (halomon, anverene, isoplocamenone, plocamenone), peptide compounds (chlorodysinosin A) and antiviral drugs (virantmycin). The structures of common halogen-containing natural products are as follows:

[0003]

[0004] In addition, as important organic synthesis intermediates, organic halides have very wide applications in substitution reactions, elimination reactions, radical reactions and various coupling reactions. In recent decades, organic chemists have gradually developed a variety of methods to construct carbon-halogen bonds and synthesized a series of organic halides with diverse structures and specific structures. Among them, the dihalogenation and haloazidation reactions of 1,3-conjugated dienes are important organic transformations, which can simultaneously introduce two halogen atoms or a halogen atom and an azide group into the organic structure, and can rapidly synthesize a series of widely used bromochlorides and bromoazides. Therefore, the research on the dihalogenation and haloazidation reactions of conjugated dienes is of great significance and has received extensive attention from organic chemists.

[0005] However, there are relatively few reports on the dihalogenation and haloazidation reactions of 1,3-conjugated dienes at present, and the existing reports often have great limitations. For example, in 2015, the Burns research group reported the highly chemo-, regio- and enantioselective bromochlorination reaction of allylic alcohols catalyzed by chiral Schiff base (Hu, D. X.; Seidl, F. J.; Bucher, C.; Burns, N. Z. J. Am. Chem. Soc. 2015, 137, 3795-3798.). This method uses NBS and titanium(IV) isopropoxide as halogenating reagents and can achieve the bromochlorination reaction of conjugated dienes with high regioselectivity and enantioselectivity. In 2018, this research group also reported the highly regio- and stereoselective haloazidation reaction of allylic alcohols (Seidl, F. J.; Min, C.; Lopez, J. A.; Burns, N. Z. J. Am. Chem. Soc. 2018, 140, 15646-15650.). Among them, the authors reported the first example of enantioselective 1,4-haloazidation reaction of conjugated dienes using (E)-hex-2-en-4-en-1-ol as the substrate and NBS as the electrophilic halogen source. However, in the above reports, the conjugated dienes used have special structures, with large substrate limitations, and each article only involves one example of conjugated dienes. In 2022, the Bayeh-Romero research group reported a new strategy for the bromochlorination reaction of unsaturated systems catalyzed by Lewis bases (Lubaev, A. E.; Rathnayake, M. D.; Eze, F.; Bayeh-Romero, L. J. Am. Chem. Soc. 2022, 144, 13294-13301.). This method uses SOCl 2 as the chlorine source and uses as low as 1 mol% of triphenylphosphine or triphenylphosphine oxide as the Lewis base activator. However, unfortunately, for some conjugated diene substrates (such as isoprene, etc.), this reaction shows poor reactivity and selectivity.

[0006] In addition to the methods mentioned above, early reports on the dihalogenation and haloazidation reactions of conjugated dienes have been reported, but in these reaction systems, halogenating reagents with high toxicity and corrosiveness are often used, such as Cl 2 , Br 2 , BrN 3 , IN 3 etc. This not only brings great difficulties and dangers to experimental operations, but also poses great potential safety hazards during the transportation and storage of reagents. In the existing reports, the structures of the substrates are often relatively special, with poor generality, and the control of reaction selectivity is often difficult. For 1,3-conjugated dienes with simple structures and easy synthesis, no suitable strategy has been developed to achieve the selective control of their dihalogenation and haloazidation reactions. Summary of the Invention

[0007] In view of the problems existing in the above-mentioned prior art, the present invention aims to provide a method for preparing bromochlorides or bromoazides using 1,3-conjugated dienes as substrates. The present invention uses a variety of 1,3-conjugated dienes as raw materials, and realizes the preparation of a series of bromochlorides or bromoazides through a new strategy of dihalogenation and haloazidation reactions, thereby overcoming the above-mentioned defects of the prior art. In addition, through a series of derivatization reactions, we have demonstrated the synthetic application value of the above products (i.e., bromochlorides or bromoazides).

[0008] The present invention uses 1,3-conjugated dienes as substrates and adopts a one-step method to prepare bromochlorides or bromoazides, which specifically includes the following steps:

[0009] Under an argon atmosphere, add the substrate 1,3-conjugated diene (i.e., Compound of Formula 1) to a 15 mL sealed tube, add an organic solvent, place the reaction mixture at 0 °C, sequentially add a nucleophile and a bromine positive reagent, stir the mixture at 0 °C until the reaction is complete (monitor the reaction using TLC); quench the reaction with a saturated aqueous sodium thiosulfate solution and extract with dichloromethane, dry the combined organic phases with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and purify the crude product by preparative HPLC (using a Shimadzu Shim-Pack PRC-ODS chromatographic column, using MeCN as the mobile phase, with a flow rate of 5 mL / min) or column chromatography or preparative thin layer chromatography (the eluent is composed of a mixture of ethyl acetate and petroleum ether) to obtain bromochlorides or bromoazides.

[0010] The reaction route is as follows:

[0011]

[0012]

[0013] During the reaction, the molar ratio of 1,3-conjugated diene to the nucleophile and the bromine positive reagent is 1:1.5:1.5, and the amount of dry toluene is 2 mL.

[0014] In the formula, the substituents R 1 , R 2 , R 3 , R 4 , R 5 , R 6 are each independently selected from hydrogen, alkyl or substituted alkyl, aryl or substituted aryl, halogen, etc. The substituents are substituents containing halogen, O, S, Si or N, etc.

[0015] The reaction of the present invention to obtain the target products 2 and 4 through the reaction route on the left or the target products 3 and 5 through the reaction route on the right is related to the structure of the reaction substrate.

[0016] Further, when R 2 is an aryl or alkyl group and TMSCl is a nucleophile, the product obtained is 2; when R 3 is an aryl or alkyl group and TMSCl is a nucleophile, the product obtained is 3; when R 2 is an aryl or alkyl group and TMSN 3 is a nucleophile, the product obtained is 4; when R 3 is an aryl or alkyl group and TMSN 3 is a nucleophile, the product obtained is 5.

[0017] The organic solvent is dry toluene.

[0018] The nucleophile is TMSCl or TMSN 3 (0.3 mmol, 1.0 mol / L in CH 2 Cl 2 ).

[0019] The bromine positive reagent is NBS (0.3 mmol, 0.5 mol / L in MeCN).

[0020] The present invention discloses a preparation method of bromochlorides and bromoazides, realizing the selective bromochlorination and bromoazidation reactions of 1,3-conjugated dienes, and successfully obtaining a series of bromochlorides and bromoazides with wide applications. The present invention adopts a one-step method, with mild conditions, no need for any metal and additives, simple operation, high reaction efficiency, wide substrate scope, and high yields, regioselectivities and stereoselectivities of the products. The present invention provides a new means for synthesizing various bromochlorides and bromoazides, with strong economic practicability and industrial application prospects. In addition, a series of derivatization reactions fully demonstrate the synthetic application value of the obtained bromochlorides and bromoazides Specific Embodiments

[0021] The synthesis method of 1,3-conjugated dienes mainly refers to the following literature: (a) Takaya, J.; Sasano, K.; Iwasawa, N. Org. Lett. 2011, 13, 1698 - 1701.; (b) Fiorito, D Folliet, S.; Liu, Y.; Mazet, C. ACS Catal. 2018, 8, 1392 - 1398.

[0022] Example 1: Preparation of (E)-(4-bromo-3-chlorobut-1-en-1-yl)benzene (2a)

[0023]

[0024] Under an argon atmosphere, 1a (0.2 mmol) and dry toluene (2 mL) were added to a 15 mL sealed tube. The reaction mixture was placed at 0 °C, and TMSCl (0.3 mmol, 1.0 mol / L in CH 2 Cl 2 ) and NBS (0.3 mmol, 0.5 mol / L in MeCN) were added successively. The mixture was stirred at 0 °C for 1 hour until the reaction was complete (monitored by TLC). The reaction was quenched with saturated aqueous sodium thiosulfate solution and extracted with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and the crude product was purified by preparative HPLC (using a Shimadzu Shim-Pack PRC-ODS column, with MeCN as the mobile phase and a flow rate of 5 mL / min) to obtain the target product 2a, a colorless oily liquid, with an isolated yield of 81%.

[0025] The chemical shifts and splittings of the colorless oily liquid product were analyzed by proton nuclear magnetic resonance ( 1 1H NMR) and carbon nuclear magnetic resonance ( 13 13C NMR), and the molecular weight was determined by high-resolution mass spectrometry (HRMS); 1 1H NMR (400 MHz, CDCl 3 3) δ 7.44–7.39 (m, 2H), 7.37–7.32 (m, 2H), 7.32–7.27 (m, 1H), 6.71 (d, J = 15.6 Hz, 1H), 6.18 (dd, J = 15.6, 8.8 Hz, 1H), 4.74 (tdd, J = 8.8, 5.2, 0.8 Hz, 1H), 3.77 (dd, J = 10.3, 5.2 Hz, 1H), 3.64 (dd, J = 10.3, 8.8 Hz, 1H). 13 13C NMR (101 MHz, CDCl 3 3) δ 135.52, 135.14, 128.84, 128.77, 127.06, 126.47, 60.84, 35.67. HRMS (ESI): m / z calculated for [C 10 9 10 H +-Cl]: 208.9965, found: 208.9978. It is proved that the colorless oily liquid product obtained from the above reaction is the target product 2a.

[0026] Example 2: Preparation of (E)-1-(4-bromo-3-chlorobut-1-en-1-yl)-4-chlorobenzene (2b)

[0027]

[0028] The preparation method of the target product 2b is the same as that of Example 1. Colorless oily liquid product, product yield 76%. 1 HNMR(400MHz, CDCl 3 ) δ 7.36–7.30(m, 4H), 6.66(d, J = 15.6Hz, 1H), 6.16(dd, J = 15.6, 8.8Hz, 1H), 4.72(tdd, J = 8.8, 5.0, 0.8Hz, 1H), 3.77(dd, J = 10.3, 5.0Hz, 1H), 3.63(dd, J = 10.3, 8.8Hz, 1H). 13 CNMR(101MHz, CDCl 3 ) δ 134.52, 134.01, 133.87, 129.05, 128.26, 127.12, 60.46, 35.49. HRMS(ESI): m / z calculated for [C 10 H 9 BrCl 2 + -Cl]: 242.9576, found: 242.9591.

[0029] Example 3: Preparation of (E)-1-bromo-4-(4-bromo-3-chlorobut-1-en-1-yl)benzene (2c)

[0030]

[0031] The preparation method of the target product 2c is the same as that of Example 1. Colorless oily liquid, product yield 76%. 1 H NMR(400MHz, CDCl 3) δ 7.49–7.45 (m, 2H), 7.30–7.26 (m, 2H), 6.65 (d, J=15.6 Hz, 1H), 6.18 (ddd, J=15.6, 8.8, 0.6 Hz, 1H), 4.79–4.67 (m, 1H), 3.77 (ddd, J=10.3, 5.0, 0.6 Hz, 1H), 3.66–3.59 (m, 1H). 13 C NMR(101MHz,CDCl 3 ) δ 134.43, 133.93, 132.00, 128.54, 127.21, 122.72, 60.44, 35.45. HRMS(ESI): m / z calculated for [C 10 H 9 Br 2 Cl + -Cl]: 286.9071, found: 286.9069.

[0032] Example 4: Preparation of (E)-1-(4-bromo-3-chlorobut-1-en-1-yl)-4-fluorobenzene (2d)

[0033]

[0034] The preparation method of the target product 2d is the same as that of Example 1. Colorless oily liquid, product yield 82%. 1 H NMR(400MHz,CDCl 3 ) δ 7.42–7.36 (m, 2H), 7.08–7.00 (m, 2H), 6.67 (d, J=15.6 Hz, 1H), 6.10 (dd, J=15.6, 8.9 Hz, 1H), 4.73 (tdd, J=8.9, 5.1, 0.8 Hz, 1H), 3.77 (dd, J=10.3, 5.1 Hz, 1H), 3.63 (dd, J=10.3, 8.9 Hz, 1H). 19 F NMR(376MHz,CDCl 3 ) δ -112.65 (tt, J=8.8, 5.4 Hz). 13 C NMR(101MHz,CDCl 3)δ163.05(d, J = 248.4Hz), 133.95, 131.70(d, J = 3.3Hz), 128.71(d, J = 8.2Hz), 126.26(d, J = 2.3Hz), 115.85(d, J = 21.8Hz), 60.66, 35.60. HRMS(ESI): m / z calculated for [C 10 H 9 BrClF + -Cl]: 226.9871, found: 226.9880.

[0035] Example 5: Preparation of (E)-1-(4-bromo-3-chlorobut-1-en-1-yl)-3-methylbenzene (2e)

[0036]

[0037] The preparation method of the target product 2e is the same as that of Example 1. Colorless oily liquid, the product yield is 86%. 1 H NMR(400 MHz, CDCl 3 )δ7.25–7.18(m, 3H), 7.15–7.09(m, 1H), 6.67(d, J = 15.6Hz, 1H), 6.16(dd, J = 15.6, 8.9Hz, 1H), 4.73(td, J = 8.9, 5.1Hz, 1H), 3.76(dd, J = 10.3, 5.1Hz, 1H), 3.63(dd, J = 10.3, 8.9Hz, 1H), 2.35(s, 3H). 13 C NMR(101 MHz, CDCl 3 )δ138.45, 135.44, 135.27, 129.57, 128.73, 127.69, 126.25, 124.28, 60.95, 35.71, 21.51. HRMS(ESI): m / z calculated for [C 11 H 12 BrCl + -Cl]: 223.0122, found: 223.0126.

[0038] Example 6: Preparation of (E)-1-(4-bromo-3-chlorobut-1-en-1-yl)-2-methylbenzene (2f)

[0039]

[0040] The preparation method of the target product 2f is the same as that of Example 1. It is a colorless oily liquid with a product yield of 77%. 1 H NMR(400MHz,CDCl 3 )δ7.47–7.43(m,1H),7.21–7.14(m,3H),6.92(d,J=15.5Hz,1H),6.05(dd,J=15.5,8.9Hz,1H),4.75(tdd,J=8.9,5.1,0.8Hz,1H),3.78(dd,J=10.3,5.1Hz,1H),3.63(dd,J=10.3,8.9Hz,1H),2.37(s,3H). 13 C NMR(101MHz,CDCl 3 )δ136.14,134.74,133.07,130.56,128.58,127.88,126.35,126.20,60.91,35.65,19.91.HRMS(ESI):m / z calculatedfor[C 11 H 12 BrCl + -Cl]:223.0122,found:223.0125.

[0041] Example 7: Preparation of (E)-5-(4-bromo-3-chlorobut-1-en-1-yl)benzo[d][1,3]dioxole (2g)

[0042]

[0043] The preparation method of the target product 2g is the same as that of Example 1. It is a colorless oily liquid with a product yield of 73%. 1 H NMR(400MHz,CDCl 3 )δ6.95(d,J=1.7Hz,1H),6.85(m,1H),6.77(d,J=7.9Hz,1H),6.61(d,J=15.6Hz,1H),6.00(dd,J=15.6,8.9Hz 1H),5.97(s,2H),4.72(tdd,J=8.9,5.1,0.8Hz,1H),3.76(dd,J=10.3,5.1Hz,1H),3.63(dd,J=10.3,8.9Hz,1H). 13 C NMR(101MHz,CDCl 3)δ148.30,148.24,134.82,129.90,124.67,122.21,108.51,106.13,101.41,61.10,35.78.HRMS(ESI):m / zcalculated for[C 11 H 10 BrClO 2 + -Cl]:288.9631,found:288.9636.

[0044] Example 8: Preparation of (E)-2-(4-bromo-3-chlorobut-1-en-1-yl)naphthalene (2h)

[0045]

[0046] The preparation method of the target product 2h is the same as that of Example 1. Colorless oily liquid, the product yield is 95%. 1 H NMR(400MHz,CDCl 3 )δ7.84–7.76(m,4H),7.61–7.57(m,1H),7.51–7.43(m,2H),6.86(d,J = 15.6Hz,1H),6.30(dd,J = 15.6,8.8Hz,1H),4.79(td,J = 8.8,5.2Hz,1H),3.79(dd,J = 10.3,5.2Hz,1H),3.67(dd,J = 10.3,8.8Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ135.25,133.56,133.56,132.95,128.57,128.28,127.85,127.60,126.75,126.62,126.55,123.61,60.95,35.72.HRMS(ESI):m / zcalculated for[C 14 H 12 BrCl + -Cl]:259.0122,found:259.0134.

[0047] Example 9: Preparation of (E)-1-(4-bromo-3-chlorobut-1-en-1-yl)naphthalene (2i)

[0048]

[0049] The preparation method of the target product 2i is the same as that of Example 1. It is a colorless oily liquid with a product yield of 92%. 1 H NMR(400MHz,CDCl 3 )δ8.13–8.02(m,1H),7.90–7.77(m,2H),7.67–7.58(m,1H),7.57–7.44(m,4H),6.21(dd,J=15.4,8.8Hz,1H),4.87(tdd,J=8.8,5.1,0.9Hz,1H),3.83(dd,J=10.3,5.Hz,1H),3.69(dd,J=10.3,9.0Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ133.72,133.32,132.53,131.26,129.67,129.02,128.75,126.55,126.13,125.67,124.63,123.77,60.62,35.60.HRMS(ESI):m / zcalculated for[C 14 H 12 BrCl + -Cl]:259.0122,found:259.0115.

[0050] Example 10: Preparation of (E)-2-(4-bromo-3-chlorobut-1-en-1-yl)thiophene (2j)

[0051]

[0052] The preparation method of the target product 2j is the same as that of Example 1. It is a light yellow oily liquid with a product yield of 74%. 1 H NMR(400MHz,CDCl 3 )δ7.25–7.22(m,1H),7.06–7.03(m,1H),6.99(dd,J=5.1,3.6Hz,1H),6.83(dd,J=15.5,0.7Hz,1H),6.01(dd,J=15.5,8.8Hz,1H),4.70(tdd,J=8.8,5.2,0.8Hz,1H),3.75(dd,J=10.3,5.2Hz,1H),3.62(dd,J=10.3,8.8Hz,1H). 13 C NMR(101MHz,CDCl 3)δ140.30,128.18,127.68,127.62,125.88,125.61,60.69,35.50.HRMS(ESI):m / zcalculated for[C 8 H 8 BrClS + -Cl]:214.9530,found:214.9529.

[0053] Example 11: Preparation of (4-bromo-3-chlorobut-1-ene-1,1-diyl)dibenzene (2k)

[0054]

[0055] The preparation method of the target product 2k is the same as that of Example 1. Colorless oily liquid, product yield 77%. 1 H NMR(400MHz,CDCl 3 )δ7.46–7.35(m,3H),7.32–7.26(m,7H),6.06(d,J=10.5Hz,1H),4.68(ddd,J=10.5,9.1,5.1Hz,1H),3.69(dd,J=10.1,5.1Hz,1H),3.63(dd,J=10.1,9.1Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ147.15,140.87,138.37,129.64,128.67,128.51,128.44,128.14,127.88,125.67,57.47,35.82.HRMS(ESI):m / z calculated for[C 16 H 14 BrCl + -Cl]:285.0278,found:285.0290.

[0056] Example 12: Preparation of 4,4'-(4-bromo-3-chlorobut-1-ene-1,1-diyl)bis(fluorobenzene) (2l)

[0057]

[0058] The preparation method of the target product 2l is the same as that of Example 1. Colorless oily liquid, product yield 90%. 1 H NMR(400MHz,CDCl 3) δ 7.29–7.19 (m, 4H), 7.16–7.08 (m, 2H), 7.04–6.96 (m, 2H), δ 5.99 (d, J=10.5 Hz, 1H), 4.63 (ddd, J=10.5, 9.6, 4.8 Hz, 1H), 3.69 (dd, J=10.1, 4.8 Hz, 1H), 3.61 (dd, J=10.1, 9.6 Hz, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ 161.45 (d, J=249.9 Hz), 162.55 (d, J=249.0 Hz), 145.11, 136.76 (d, J=3.3 Hz), 133.93 (d, J=3.6 Hz), 131.23 (d, J=8.1 Hz), 129.45 (d, J=8.1 Hz), 125.83, 115.72 (d, J=21.5 Hz), 115.32 (d, J=21.6 Hz), 56.96, 35.40. 19 F NMR (376 MHz, CDCl 3 ) δ -113.08–-113.18 (m), -113.19–-113.28 (m). HRMS (ESI): m / z calculated for [C 16 H 12 BrClF 2 + -Cl]: 321.0090, found: 321.0089.

[0059] Example 13: Preparation of (E)-(4-bromo-3-chloro-3-methylbut-1-en-1-yl)benzene (2m)

[0060]

[0061] The preparation method of the target product 2m is the same as that of Example 1. Colorless oily liquid, and the product yield is 50%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.44–7.38 (m, 2H), 7.38–7.31 (m, 3H), 6.70 (d, J=15.9 Hz, 1H), 6.35 (d, J=15.9 Hz, 1H), 3.81 (d, J=10.3 Hz, 1H), 3.77 (d, J=10.3 Hz, 1H), 1.94 (s, 3H). 13 C NMR (101 MHz, CDCl 3) δ 135.84, 131.44, 131.20, 128.83, 128.53, 127.02, 69.00, 42.59, 27.81. HRMS(ESI): m / z calculated for [C 11 H 12 BrCl + -Cl]: 223.0122, found: 223.0119.

[0062] Example 14: Preparation of (E)-(4-bromo-3-chloropent-1-en-1-yl)benzene (2n)

[0063]

[0064] The preparation method of the target product 2n is the same as that of Example 1. Colorless oily liquid, product yield 70%, dr = 1:1. 1 H NMR (400 MHz, CDCl 3 ) δ 7.44–7.40 (m, 2H), 7.37–7.32 (m, 2H), 7.31–7.26 (m, 1H), 6.74–6.64 (m, 1H), 6.36–6.22 (m, 1H), 4.80–4.60 (m, 1H), 4.43–4.25 (m, 1H), 1.86–1.79 (m, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 135.72, 135.67, 135.25, 134.70, 128.83, 128.67, 127.05, 127.03, 126.85, 124.68, 67.20, 66.20, 52.18, 51.62, 23.45, 21.26. HRMS(ESI): m / z calculated for [C 11 H 12 BrCl + -Cl]: 223.0122, found: 223.0114.

[0065] Example 15: Preparation of (E)-((2-bromo-3-chloro-5-phenylpent-4-en-1-yl)oxy)(tert-butyl)dimethylsilane (2o)

[0066]

[0067] The preparation method of the target product 2o is the same as that of Example 1. Colorless oily liquid, product yield 90%, dr = 1:1.3.1 HNMR(400MHz,CDCl 3 )δ7.43–7.38(m,2H),7.37–7.31(m,2H),7.30–7.25(m,1H),6.72–6.63(m,1H),6.43–6.25(m,1H),5.02–4.91(m,1H),4.30–4.18(m,1H),4.08–3.95(m,1H),3.95–3.81(m,1H),0.97–0.88(m,9H),0.15–0.05(m,6H). 13 C NMR(101MHz,CDCl 3 )δ135.77,135.76,134.91,133.75,128.81,128.61,128.58,127.21,127.04,126.15,64.85,64.64,62.11,61.77,58.24,57.68,25.97,18.44,18.43,-5.19,-5.23,-5.25.HRMS(ESI):m / z calculated for[C 17 H 26 BrClOSi + -Cl]:353.0936,found:353.0953.

[0068] Example 16: Preparation of (E)-2-bromo-3-chloro-5-phenylpent-4-en-1-yl benzoate (2p)

[0069]

[0070] The preparation method of the target product 2p is the same as that of Example 1. It is a colorless oily liquid with a product yield of 79% and dr = 1:1.2. 1 HNMR(400MHz,CDCl 3 )δ8.10–8.04(m,2H),7.62–7.56(m,1H),7.49–7.38(m,4H),7.36–7.26(m,3H),6.76–6.68(m,1H),6.42–6.28(m,1H),4.96–4.87(m,1H),4.82–4.71(m,2H),4.59–4.48(m,1H). 13 C NMR(101MHz,CDCl 3)δ165.90,165.86,135.42,135.41,135.35,134.93,133.58,129.93,129.92,129.53,129.49,128.85,128.81,128.67,127.10,125.91,125.42,65.71,65.27,62.60,62.29,53.46,53.31.HRMS(ESI):m / z calculated for[C 18 H 16 BrClO 2 + -Cl]:343.0333,found:343.0314.

[0071] Example 17: Preparation of (E)-(4-bromo-3-chlorooct-1-en-1-yl)benzene (2q)

[0072]

[0073] The preparation method of the target product 2q is the same as that of Example 1. Colorless oily liquid, product yield 74%, dr = 1:1.2). 1 H NMR(400MHz,CDCl 3 )δ7.44–7.39(m,2H),7.37–7.31(m,2H),7.31–7.26(m,1H),6.73–6.63(m,1H),6.40–6.24(m,1H),4.85–4.65(m,1H),4.26–4.16(m,1H),2.18–2.01(m,1H),1.95–1.80(m,1H),1.69–1.56(m,1H),1.50–1.27(m,3H),0.97–0.90(m,3H). 13 C NMR(101MHz,CDCl 3 )δ135.76,135.74,134.74,134.55,128.82,128.63,128.62,127.04,127.03,127.01,125.58,65.75,65.72,59.61,59.09,35.50,34.09,29.90,29.44,22.17,22.14,14.06.HRMS(ESI):m / z calculated for[C 14 H 18 BrCl + -Cl]:265.0591,found:265.0600.

[0074] Example 18: Preparation of (E)-(4-bromo-3-chloro-4-methylpent-1-en-1-yl)benzene (2r)

[0075]

[0076] The preparation method of the target product 2r is the same as that of Example 1. It is a colorless oily liquid with a product yield of 60%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.45–7.40 (m, 2H), 7.37–7.31 (m, 2H), 7.31–7.27 (m, 1H), 6.68 (d, J = 15.6 Hz, 1H), 6.40 (ddd, J = 15.6, 9.0, 1.0 Hz, 1H), 4.64 (d, J = 9.0 Hz, 1H), 1.90 (s, 3H), 1.88 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 135.81, 134.89, 128.81, 128.58, 127.01, 126.22, 71.99, 66.78, 32.62, 30.05. HRMS (ESI): m / z calculated for [C 12 H 14 BrCl + -Cl]: 237.0278, found: 237.0303.

[0077] Example 19: Preparation of (2-(3-bromo-2-chloropropylidene)propane-1,3-diyl)dibenzene (2s)

[0078]

[0079] The preparation method of the target product 2s is the same as that of Example 1. It is a colorless oily liquid with a product yield of 52%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.34–7.27 (m, 5H), 7.23–7.11 (m, 5H), 5.48 (d, J = 9.9 Hz, 1H), 5.01 (td, J = 9.9, 4.8 Hz, 1H), 3.74 (dd, J = 9.9, 4.8 Hz, 1H), 3.58 (dd, J = 9.9, 9.6 Hz, 1H), 3.49 (d, J = 15.1 Hz, 1H), 3.33 (d, J = 15.1 Hz, 1H), 3.28 (s, 2H).13 C NMR (101 MHz, CDCl 3 ) δ 144.95, 138.58, 138.27, 129.30, 129.03, 128.74, 128.60, 126.72, 126.62, 126.59, 55.81, 42.77, 36.07, 35.92. HRMS (ESI): m / z calculated for [C 18 H 18 BrCl + -Cl]: 313.0591, found: 313.0598.

[0080] Example 20: Preparation of (Z)-(1-bromo-4-chlorobut-2-en-2-yl)benzene (3a)

[0081]

[0082] The preparation method of the target product 3a is the same as that of Example 1. Colorless oily liquid, product yield 77%, Z / E = 77:23, 3a:3a' > 98:2. 1 H NMR (400 MHz, CDCl 3 ) δ 7.49–7.45 (m, 2H), 7.42–7.37 (m, 2H), 7.36 (m, 1H), 6.12 (t, J = 8.1 Hz, 1H), 4.38 (s, 2H), 4.32 (d, J = 8.1 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 141.00, 139.04, 128.80, 128.67, 128.10, 126.36, 39.65, 27.09. HRMS (ESI): m / z calculated for [C 10 H 10 BrCl + -Cl]: 208.9965, found: 208.9973.

[0083] Example 21: Preparation of (Z)-1-(1-bromo-4-chlorobut-2-en-2-yl)-4-chlorobenzene (3b)

[0084]

[0085] The preparation method of the target product 3b is the same as that of Example 1. Colorless oily liquid, product yield 76%, Z / E = 78:22, 3b:3b' = 98:2.1 H NMR (400 MHz, CDCl 3 ) δ 7.41–7.38 (m, 2H), 7.36–7.33 (m, 2H), 6.10 (t, J = 8.0 Hz, 1H), 4.33 (s, 2H), 4.29 (d, J = 8.0 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 139.90, 137.44, 134.61, 128.99, 128.45, 127.68, 39.42, 26.74. HRMS (ESI): m / z calculated for [C 10 H 9 BrCl 2 + -Cl]: 242.9576, found: 242.9576.

[0086] Example 22: Preparation of (Z)-1-(1-bromo-4-chlorobut-2-en-2-yl)-4-fluorobenzene (3c)

[0087]

[0088] The target product 3c was prepared in the same manner as in Example 1. It was a colorless oily liquid with a product yield of 80%, Z / E = 79:21, and 3c:3c' = 97:3. 1 H NMR (400 MHz, CDCl 3 ) δ 7.47–7.42 (m, 2H), 7.09–7.04 (m, 2H), 6.07 (t, J = 8.1 Hz, 1H), 4.34 (s, 2H), 4.30 (d, J = 8.1 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 162.99 (d, J = 248.4 Hz), 140.04, 135.12 (d, J = 3.4 Hz), 128.16 (d, J = 8.1 Hz), 128.01 (d, J = 1.4 Hz), 115.75 (d, J = 21.6 Hz), 39.51, 27.04. 19 F NMR (376 MHz, CDCl 3 ) δ -113.16 (ddd, J = 13.9, 8.7, 5.3 Hz). HRMS (ESI): m / z calculated for [C 10 H 9 BrClF +-Cl]: 226.9871, found: 226.9878.

[0089] Example 23: Preparation of (Z)-1-(1-bromo-4-chlorobut-2-en-2-yl)-4-(tert-butyl)benzene (3d)

[0090]

[0091] The preparation method of the target product 3d is the same as that of Example 1. Colorless oily liquid, product yield 74%, Z / E = 78:22, 3d:3d' = 96:4. 1 H NMR (400 MHz, CDCl 3 ) δ 7.42–7.40 (m, 4H), 6.13 (t, J = 8.1 Hz, 1H), 4.38 (s, 2H), 4.32 (d, J = 8.1 Hz, 2H), 1.33 (s, 9H). 13 C NMR (101 MHz, CDCl 3 ) δ 151.82, 140.68, 135.87, 127.30, 125.93, 125.74, 39.79, 34.75, 31.38, 27.05. HRMS (ESI): m / z calculated for [C 14 H 18 BrCl + -Cl]: 265.0591, found: 265.0592.

[0092] Example 24: Preparation of (Z)-1-(1-bromo-4-chlorobut-2-en-2-yl)-4-methoxybenzene (3e)

[0093]

[0094] The preparation method of the target product 3e is the same as that of Example 1. Colorless oily liquid, product yield 83%, Z / E = 84:16, 3e:3e' = 97:3. 1 H NMR (400 MHz, CDCl 3 ) δ 7.44–7.39 (m, 2H), 6.92–6.88 (m, 2H), 6.06 (t, J = 8.1 Hz, 1H), 4.36 (s, 2H), 4.31 (d, J = 8.1 Hz, 2H), 3.83 (s, 3H). 13 C NMR (101 MHz, CDCl 3)δ160.04,140.53,129.69,127.56,126.30,114.18,55.47,39.87,27.17.HRMS(ESI):m / zcalculated for[C 11 H 12 BrClO + -Cl]:239.0071,found:239.0075.

[0095] Example 25: Preparation of (Z)-((4-(1-bromo-4-chlorobut-2-en-2-yl)phenyl)ethynyl)trimethylsilane (3f)

[0096]

[0097] The preparation method of the target product 3f is the same as that of Example 1. Colorless oily liquid, the product yield is 70%, Z / E = 81:19, 3f:3f' = 93:7. 1 H NMR(400MHz,CDCl 3 )δ7.48–7.45(m,2H),7.43–7.38(m,2H),6.15(t,J = 8.1Hz,1H),4.34(s,2H),4.31(d,J = 8.1Hz,2H),0.26(s,9H). 13 C NMR(101MHz,CDCl 3 )δ140.29,138.88,132.37,128.57,128.40,126.14,104.67,95.76,39.50,26.61,0.09.HRMS(ESI):m / z calculated for[C 15 H 18 BrClSi + -Cl]:305.0361,found:305.0360.

[0098] Example 26: Preparation of (Z)-4-(1-bromo-4-chlorobut-2-en-2-yl)-1,1'-biphenyl (3g)

[0099]

[0100] The preparation method of the target product 3g is the same as that of Example 1. Colorless oily liquid, the product yield is 75%, Z / E = 82:18, 3g:3g' = 93:7. 1 H NMR(400MHz,CDCl3 ) δ 7.60 (m, 4H), 7.56–7.53 (m, 2H), 7.47–7.42 (m, 2H), 7.38–7.34 (m, 1H), 6.19 (t, J = 8.1 Hz, 1H), 4.40 (s, 2H), 4.33 (d, J = 8.1 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 141.50, 140.53, 140.44, 137.74, 128.98, 127.89, 127.71, 127.47, 127.15, 126.72, 39.68, 26.92. HRMS (ESI): m / z calculated for [C 16 H 14 BrCl + -Cl]: 285.0278, found: 285.0283.

[0101] Example 27: Preparation of (Z)-1-(1-bromo-4-chlorobut-2-en-2-yl)-3,5-dimethylbenzene (3h)

[0102]

[0103] The preparation method of the target product 3h is the same as that of Example 1. Colorless oily liquid, the product yield is 78%, Z / E = 76:24, 3h:3h' = 94:6. 1 H NMR (400 MHz, CDCl 3 ) δ 7.08–7.06 (m, 2H), 7.00–6.98 (m, 1H), 6.09 (t, J = 8.1 Hz, 1H), 4.36 (s, 2H), 4.30 (d, J = 8.1 Hz, 2H), 2.34 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ 141.24, 138.99, 138.31, 130.35, 127.72, 124.20, 39.75, 27.31, 21.51. HRMS (ESI): m / z calculated for [C 12 H 14 BrCl + -Cl]: 237.0278, found: 237.0281.

[0104] Example 28: Preparation of

[0105] 1-((Z)-1-bromo-4-chlorobut-2-en-2-yl)-4-(((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)benzene(3i)

[0106]

[0107] The preparation method of the target product 3i is the same as that of Example 1. It is a colorless oily liquid, the product yield is 50%, Z / E = 90:10, 3i:3i' = 97:3. 1 H NMR(400MHz,CDCl 3 )δ7.42–7.37(m,2H),6.91–6.86(m,2H),6.07(t,J = 8.1Hz,1H),4.65(m,1H)4.37(s,2H),4.31(d,J = 8.1Hz,2H),2.15–2.04(m,1H),1.82–1.61(m,6H),1.11–0.98(m,2H),0.93(d,J = 6.7Hz,3H),0.85(d,J = 6.6Hz,3H),0.82(d,J = 6.6Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ158.81,140.56,129.69,127.52,125.98,115.67,73.45,47.87,39.98,37.73,35.10,29.41,27.16,26.32,24.96,22.42,21.20,20.99.HRMS(ESI):m / z calculated for[C 20 H 28 BrClO + -Cl]:363.1323,found:363.1317.

[0108] Example 29: Preparation of (Z)-4-(1-bromo-4-chlorobut-2-en-2-yl)phenyl 2-(2-fluoro-[1,1'-biphenyl]-4-yl)propanoate(3j)

[0109]

[0110] The preparation method of the target product 3j is the same as that of Example 1. It is a colorless oily liquid, the product yield is 76%, Z / E = 83:17, 3j:3j' = 98:2. 1 H NMR(400MHz,CDCl3 )δ 7.57–7.54 (m, 2H), 7.47–7.42 (m, 5H), 7.41–7.35 (m, 1H), 7.27–7.23 (m, 2H), 7.08–7.03 (m, 2H), 6.08 (t, J = 8.1 Hz, 1H), 4.32 (s, 2H), 4.28 (d, J = 8.1 Hz, 2H), 4.00 (q, J = 7.1 Hz, 1H), 1.66 (d, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 )δ 172.45, 159.90 (d, J = 248.7 Hz), 150.95, 141.21 (d, J = 7.7 Hz), 140.08, 136.79, 135.47, 131.17 (d, J = 4.0 Hz), 129.58, 129.08 (d, J = 3.0 Hz), 128.61, 128.32, 127.89, 127.47, 123.71 (d, J = 3.4 Hz), 121.69, 115.45 (d, J = 23.8 Hz), 45.27, 39.50, 26.93, 18.52. HRMS (ESI): m / z calculated for [C 25 H 21 BrClFO 2 + -Cl]: 451.0708, found: 451.0707.

[0111] Example 30: Preparation of (Z)-4-(1-bromo-4-chlorobut-2-en-2-yl)phenyl 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoate (3k)

[0112]

[0113] The preparation method of the target product 3k is the same as that of Example 1. A pale yellow oily liquid, the product yield is 80%, Z / E = 82:18, 3k:3k' = 98:2. 1 H NMR (400 MHz, CDCl 3)δ 7.49–7.43 (m, 2H), 7.07–7.02 (m, 2H), 7.00 (d, J = 7.4 Hz, 1H), 6.67 (d, J = 7.4 Hz, 1H), 6.63 (s, 1H), 6.10 (t, J = 8.1 Hz, 1H), 4.35 (s, 2H), 4.30 (d, J = 8.1 Hz, 2H), 3.98 (m, 2H), 2.30 (s, 3H), 2.18 (s, 3H), 1.88 (m, 4H), 1.37 (s, 6H). 13 C NMR (101 MHz, CDCl 3 )δ 176.33, 156.99, 151.33, 140.24, 136.63, 136.57, 130.50, 128.23, 127.46, 123.76, 121.90, 120.93, 112.11, 67.90, 42.64, 39.54, 37.29, 26.97, 25.42, 25.28, 21.56, 15.95. HRMS (ESI): m / z calculated for [C 25 H 30 BrClO 3 + -Cl]: 457.1378, found: 457.1384.

[0114] Example 31: Preparation of (E)-(3-azido-4-bromobut-1-en-1-yl)benzene (4a)

[0115]

[0116] Under an argon atmosphere, 1a (0.2 mmol) and dry toluene (2 mL) were added to a 15 mL sealed tube. The reaction mixture was placed at 0 °C, and TMSN 3 (0.3 mmol, 1.0 mol / L in CH 2 Cl 2 ) and NBS (0.3 mmol, 0.5 mol / L in MeCN) were added successively. The mixture was stirred at 0 °C for 4 hours until the reaction was complete (monitored by TLC). The reaction was quenched with saturated aqueous sodium thiosulfate solution and extracted with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and the crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:20) to obtain the target product 4a, a colorless oily liquid, with a separation yield of 90% for the product. 1 H NMR (400 MHz, CDCl 3) δ 7.45–7.39 (m, 2H), 7.38–7.27 (m, 3H), 6.73 (d, J = 15.8 Hz, 1H), 6.14 (dd, J = 15.8, 7.9 Hz, 1H), 4.35 (dddd, J = 7.9, 6.6, 5.4, 1.0 Hz, 1H), 3.50–3.41 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 135.70, 135.51, 128.89, 128.80, 126.99, 123.99, 64.83, 34.36. HRMS (ESI): m / z calculated for C 10 H 10 BrN 3 [M - N 3 + : 208.9966, found: 208.9967. It was proved that the colorless oily liquid product obtained from the above reaction was the target product (4a).

[0117] Example 32: Preparation of (E)-1-(3-azido-4-bromobut-1-en-1-yl)-4-chlorobenzene (4b)

[0118]

[0119] The preparation method of the target product 4b was the same as that of Example 30. Colorless oily liquid, product yield 91% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.37–7.30 (m, 4H), 6.68 (d, J = 15.8 Hz, 1H), 6.11 (dd, J = 15.8, 7.8 Hz, 1H), 4.34 (dddd, J = 7.8, 6.6, 5.5, 1.0 Hz, 1H), 3.53–3.38 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 134.55, 134.35, 133.99, 129.08, 128.19, 124.70, 64.61, 34.19. HRMS (ESI): m / z calculated for C 10 H 9 BrClN 3 [M - N 3 + : 242.9576, found: 242.9578.

[0120] ​​Example 33: Preparation of (E)-1-(3-azido-4-bromobut-1-en-1-yl)-4-bromobenzene (4c)

[0121]

[0122] The preparation method of the target product 4c is the same as that of Example 30. Colorless oily liquid, product yield 82% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.51–7.44 (m, 2H), 7.28 (dq, J = 8.2, 1.6 Hz, 2H), 6.67 (d, J = 15.8 Hz, 1H), 6.13 (ddd, J = 15.8, 7.8, 1.4 Hz, 1H), 4.40–4.27 (m, 1H), 3.52–3.39 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 134.40, 132.03, 128.47, 124.80, 122.73, 64.60, 34.16. HRMS (ESI): m / z calculated for C 10 H 9 Br 2 N 3 [M - N 3 + : 286.9071, found: 286.9075.

[0123] Example 34: Preparation of (E)-1-(3-azido-4-bromobut-1-en-1-yl)-4-fluorobenzene (4d)

[0124]

[0125] The preparation method of the target product 4d is the same as that of Example 30. Colorless oily liquid, product yield 92% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.42–7.36 (m, 2H), 7.07–7.01 (m, 2H), 6.69 (d, J = 15.8 Hz, 1H), 6.06 (dd, J = 15.8, 7.9 Hz, 1H), 4.34 (dddd, J = 7.9, 6.6, 5.5, 1.0 Hz, 1H), 3.50–3.40 (m, 2H). 19 F NMR (376 MHz, CDCl 3 ​) δ -112.58 (ddd, J=13.8, 8.7, 5.4 Hz). 13 C NMR (101 MHz, CDCl 3 ) δ 163.05 (d, J=248.6 Hz), 134.47, 131.69 (d, J=3.3 Hz), 128.63 (d, J=8.1 Hz), 123.78 (d, J=2.3 Hz), 115.88 (d, J=21.7 Hz), 64.71, 34.30. HRMS (ESI): m / z calculated for C 10 H 9 BrFN 3 [M - N 3 + : 226.9872, found: 226.9873.

[0126] Example 35: Preparation of (E)-1-(3-azido-4-bromobut-1-en-1-yl)-3-methylbenzene (4e)

[0127]

[0128] The preparation method of the target product 4e is the same as that in Example 30. Colorless oily liquid, the product yield is 89% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.28–7.18 (m, 3H), 7.14–7.07 (m, 1H), 6.70 (d, J=15.8 Hz, 1H), 6.12 (dd, J=15.8, 7.9 Hz, 1H), 4.33 (dddd, J=7.9, 6.6, 5.5, 1.0 Hz, 1H), 3.53–3.37 (m, 2H) 2.36 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 138.52, 135.85, 135.44, 129.60, 128.78, 127.64, 124.18, 123.72, 64.89, 34.39, 21.49. HRMS (ESI): m / z calculated for C 11 H 12 BrN 3 [M - N 3 + : 223.0123, found: 223.0126.

[0129] ​​Example 36: Preparation of (E)-1-(3-azido-4-bromobut-1-en-1-yl)-2-methylbenzene (4f)

[0130]

[0131] The preparation method of the target product 4f is the same as that of Example 30. Colorless oily liquid, product yield 85% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.28–7.18 (m, 3H), 7.14–7.07 (m, 1H), 6.70 (d, J = 15.8 Hz, 1H), 6.12 (dd, J = 15.8, 7.9 Hz, 1H), 4.33 (dddd, J = 7.9, 6.6, 5.5, 1.0 Hz, 1H), 3.53–3.37 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 138.52, 135.85, 135.44, 129.60, 128.78, 127.64, 124.18, 123.72, 64.89, 34.39, 21.49. HRMS (ESI): m / z calculated for C 11 H 12 BrN 3 [M - N 3 + : 223.0123, found: 223.0121.

[0132] Example 37: Preparation of (E)-2-(3-azido-4-bromobut-1-en-1-yl)naphthalene (4g)

[0133]

[0134] The preparation method of the target product 4g is the same as that of Example 30. Colorless oily liquid, product yield 85% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.86–7.77 (m, 4H), 7.60 (dd, J = 8.6, 1.8 Hz, 1H), 7.53–7.44 (m, 2H), 6.88 (d, J = 15.8 Hz, 1H), 6.25 (dd, J = 15.8, 7.9 Hz, 1H), 4.40 (dddd, J = 7.9, 6.6, 5.4, 1.0 Hz, 1H), 3.54–3.43 (m, 2H).​13 C NMR (101 MHz, CDCl 3 ) δ 135.75, 133.55, 132.90, 128.61, 128.27, 127.85, 127.56, 126.67, 126.59, 124.22, 123.48, 64.93, 34.42. HRMS (ESI): m / z calculated for C 14 H 12 BrN 3 [M - N 3 + : 259.0123, found: 259.0127.

[0135] Example 38: Preparation of (E)-1-(3-azido-4-bromobut-1-en-1-yl)naphthalene (4h)

[0136]

[0137] The preparation method of the target product 4h is the same as that of Example 30. Colorless oily liquid, the product yield is 95% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 8.08 (dd, J = 8.2, 1.4 Hz, 1H), 7.92–7.78 (m, 2H), 7.61 (d, J = 7.2 Hz, 1H), 7.57–7.43 (m, 4H), 6.16 (dd, J = 15.5, 7.8 Hz, 1H), 4.47 (dddd, J = 7.8, 6.6, 5.8, 1.0 Hz, 1H), 3.59–3.47 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 133.71, 133.38, 133.24, 131.18, 129.08, 128.77, 127.21, 126.60, 126.16, 125.66, 124.59, 123.69, 64.76, 34.28. HRMS (ESI): m / z calculated for C 14 H 12 BrN 3 [M - N 3 + : 259.0123, found: 259.0134.

[0138] ​​Example 39: Preparation of (E)-2-(3-azido-4-bromobut-1-en-1-yl)thiophene (4i)

[0139]

[0140] The preparation method of the target product 4i is the same as that of Example 30. It is a pale yellow oily liquid with a product yield of 62% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.24 (dt, J = 5.1, 0.9 Hz, 1H), 7.06 (dt, J = 3.6, 0.9 Hz, 1H), 6.99 (dd, J = 5.1, 3.6 Hz, 1H), 6.86 (dq, J = 15.6, 0.8 Hz, 1H), 5.96 (dd, J = 15.6, 7.8 Hz, 1H), 4.31 (dddd, J = 7.8, 6.6, 5.4, 1.0 Hz, 1H), 3.50–3.38 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 140.33, 128.52, 127.72, 127.59, 125.79, 123.20, 64.72, 34.20. HRMS (ESI): m / z calculated for [C 8 H 8 BrN 3 S + -N 3 : 214.9530, found: 214.9533.

[0141] Example 40: Preparation of (3-azido-4-bromobut-1-ene-1,1-diyl)dibenzene (4j)

[0142]

[0143] The preparation method of the target product 4j is the same as that of Example 30. It is a colorless oily liquid with a product yield of 72% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.46–7.37 (m, 3H), 7.33–7.26 (m, 5H), 7.24–7.19 (m, 2H), 6.05 (d, J = 9.8 Hz, 1H), 4.30 (dt, J = 9.8, 6.1 Hz, 1H), 3.45–3.37 (m, 2H). 13 C NMR (101 MHz, CDCl3 ) δ 148.87, 140.62, 138.35, 129.72, 128.84, 128.61, 128.51, 128.21, 127.72, 122.90, 60.74, 34.66. HRMS(ESI): m / z calculated for [C 16 H 14 BrN 3 + -N 3 : 285.0279, found: 285.0280.

[0144] Example 41: Preparation of 4,4'-(3-azido-4-bromobut-1-ene-1,1-diyl)bis(fluorobenzene) (4k)

[0145]

[0146] The preparation method of the target product 4k is the same as that of Example 30. Colorless oily liquid, the product yield is 78% (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.26–7.21 (m, 2H), 7.21–7.10 (m, 4H), 7.05–6.97 (m, 2H), 5.99 (d, J = 9.8 Hz, 1H), 4.25 (dt, J = 9.8, 6.2 Hz, 1H), 3.41 (d, J = 6.2 Hz, 2H). 19 F NMR (376 MHz, CDCl 3 ) δ -112.94–-113.04 (m), -113.06–-113.15 (m). 13 C NMR (101 MHz, CDCl 3 ) δ 163.11 (d, J = 249.0 Hz), 162.70 (d, J = 249.0 Hz) 146.92, 136.67 (d, J = 3.3 Hz), 134.06 (d, J = 3.5 Hz), 131.46 (d, J = 8.1 Hz), 129.45 (d, J = 8.2 Hz), 123.24, 116.04 (d, J = 21.6 Hz), 115.54 (d, J = 21.6 Hz), 60.60, 34.34. HRMS(ESI): m / z calculated for [C 16 H 12 BrF 2 N 3 + -N3 :321.0091,found:321.0095.

[0147] Example 42: Preparation of (E)-(3-azido-4-bromo-3-methylbut-1-en-1-yl)benzene (4l)

[0148]

[0149] The preparation method of the target product 4l is the same as that of Example 30. Colorless oily liquid, product yield 72% (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3 )δ7.44–7.39(m,2H),7.37–7.27(m,3H),6.71(d,J=16.1Hz,1H),6.21(d,J=16.1Hz,1H),3.51–3.44(m,2H),1.65(s,3H). 13 C NMR(101MHz,CDCl 3 )δ135.78,132.27,128.85,128.56,126.91,63.89,40.76,22.85.HRMS(ESI):m / zcalculated for[C 11 H 12 BrN 3 + -N 3 :223.0123,found:223.0118.

[0150] Example 43: Preparation of (E)-(3-azido-4-bromooct-1-en-1-yl)benzene (4m)

[0151]

[0152] The preparation method of the target product 4m is the same as that of Example 30, and the reaction time is extended to 10 hours. Colorless oily liquid, product yield 92%, dr = 1:1.3 (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3) δ 7.47–7.40 (m, 2H), 7.40–7.27 (m, 3H), 6.72 (d, J = 15.8 Hz, 1H), 6.33–6.19 (m, 1H), 4.28–4.21 (m, 1H), 4.11–3.95 (m, 1H), 1.96–1.74 (m, 2H), 1.65–1.56 (m, 1H), 1.46–1.26 (m, 3H), 0.95–0.87 (m, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 136.42, 135.75, 135.67, 128.87, 128.73, 128.70, 127.02, 127.00, 124.17, 123.57, 68.83, 68.63, 58.22, 58.09, 35.09, 34.67, 29.81, 29.76, 22.18, 22.16, 14.04. HRMS (ESI): m / z calculated for [C 14 H 18 BrN 3 + -N 3 : 265.0592, found: 265.0598.

[0153] Example 44: Preparation of (E)-((3-azido-2-bromo-5-phenylpent-4-en-1-yl)oxy)(tert-butyl)dimethylsilane (4n)

[0154]

[0155] The target product 4n was prepared in the same manner as in Example 30, with the reaction time extended to 10 hours. Colorless oily liquid, product yield 76%, dr = 1:1.5 (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.46–7.41 (m, 2H), 7.39–7.27 (m, 3H), 6.78–6.66 (m, 1H), 6.36–6.23 (m, 1H), 4.58–4.46 (m, 1H), 4.13–3.96 (m, 1H), 3.95–3.71 (m, 2H), 0.93–0.91 (m, 9H), 0.13–0.06 (m, 6H). 13 C NMR (101 MHz, CDCl 3)δ136.85,135.75,135.39,128.86,128.69,128.66,127.03,127.00,124.61,122.88,64.77,64.39,64.37,64.02,56.34,55.85,25.97,25.95,18.44,18.39,-5.21,-5.22,-5.28,-5.29.HRMS(ESI):m / z calculated for[C 17 H 26 BrN 3 OSi + -N 3 :353.0937,found:353.0978.

[0156] Example 45: Preparation of (E)-(3-azido-4-bromo-4-methylpent-1-en-1-yl)benzene (4o)

[0157]

[0158] The preparation method of the target product 4o is the same as that of Example 30, and the reaction time is extended to 8 hours. Colorless oily liquid, the product yield is 60% (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3 )δ7.47–7.43(m,2H),7.38–7.34(m,2H),7.33–7.28(m,1H),6.73(d,J = 15.8Hz,1H),6.31(dd,J = 15.8,8.5Hz,1H),4.01(dd,J = 8.5,0.8Hz,1H),1.80(s,3H),1.75(s,3H). 13 C NMR(101MHz,CDCl 3 )δ136.66,135.66,128.87,128.72,127.01,123.62,74.59,66.27,31.36,30.98.HRMS(ESI):m / z calculated for[C 12 H 14 BrN 3 + -N 3 :237.0279,found:237.0293.

[0159] Example 46: Preparation of (E)-(3-azido-4-bromo-3,4-dimethylpent-1-en-1-yl)benzene (4p)

[0160]

[0161] The preparation method of the target product 4p is the same as that in Example 30, and the reaction time is extended to 8 hours. Colorless oily liquid, product yield 54% (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3 )δ7.45–7.40(m,2H),7.38–7.32(m,2H),7.31–7.26(m,1H),6.71(d,J=16.0Hz,1H),6.44(d,J=16.0Hz,1H),1.83(s,3H),1.81(s,3H),1.74(s,3H). 13 C NMR(101MHz,CDCl 3 )δ136.16,132.50,128.84,128.75,128.34,126.87,72.07,70.92,30.29,30.17,20.87.HRMS(ESI):m / z calculated for[C 13 H 16 BrN 3 + -N 3 :251.0436,found:251.0470.

[0162] Example 47: Preparation of (E)-(5-azido-6-bromohex-3-en-1-yl)benzene (4q)

[0163]

[0164] The preparation method of the target product 4q is the same as that in Example 30, and the reaction time is extended to 10 hours. Colorless oily liquid, product yield 71%, 4q:4q' = 82:18, (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3)δ7.31–7.27(m,2H),7.22–7.16(m,3H),5.95(dtd,J=15.2,7.5,0.9Hz,1H),5.71(ddt,J=15.2,7.7,1.1Hz,1H),4.01–3.89(m,2H),3.89–3.81(m,1H),2.76–2.66(m,2H),1.94–1.77(m,2H). 13 CNMR(101MHz,CDCl 3 )δ140.79,132.49,130.40,128.68,128.58,126.32,62.53,35.95,31.94,31.15.HRMS(ESI):m / z calculated for[C 12 H 14 BrN 3 + -N 3 :237.0279,found:237.0277.

[0165] Example 48: Preparation of (Z)-(4-azido-1-bromobut-2-en-2-yl)benzene (5a)

[0166]

[0167] The preparation method of the target product 5a is the same as that of Example 30, and the reaction time is extended to 12 hours. Colorless oily liquid, the product yield is 87%, Z / E = 95:5, 5a:5a' > 98:2 (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3 )δ7.50–7.44(m,2H),7.41–7.33(m,3H),6.01(t,J=7.2Hz,1H),4.33(s,2H),4.09(d,J=7.2Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ141.39,139.26,128.82,128.60,126.36,126.23,48.38,27.51.HRMS(ESI):m / z calculated for[C 10 H 10 BrN 3 + -N 3 :208.9966,found:208.9952.

[0168] Example 49: Preparation of (Z)-1-(4-azido-1-bromobut-2-en-2-yl)-4-methoxybenzene (5b)

[0169]

[0170] The target product 5b was prepared in the same manner as in Example 30, with the reaction time extended to 12 h. A colorless oily liquid was obtained with a product yield of 82%, Z / E = 84:16, 5b:5b' > 98:2 (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.50–7.44 (m, 2H), 7.41–7.33 (m, 3H), 6.01 (t, J = 7.2 Hz, 1H), 4.33 (s, 2H), 4.09 (d, J = 7.2 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 141.39, 139.26, 128.82, 128.60, 126.36, 126.23, 48.38, 27.51. HRMS (ESI): m / z calculated for [C 10 H 10 BrN 3 + -N 3 : 208.9966, found: 208.9952.

[0171] Example 50: Preparation of methyl (Z)-4-(4-azido-1-bromobut-2-en-2-yl)benzoate (5c)

[0172]

[0173] The target product 5c was prepared in the same manner as in Example 30, with the reaction time extended to 12 h. A colorless oily liquid was obtained with a product yield of 79%, Z / E = 98:2, 5c:5c' = 75:25 (ethyl acetate / petroleum ether 1:10). 1 H NMR (500 MHz, CDCl 3 ) δ 8.06–8.03 (m, 2H), 7.55–7.52 (m, 2H), 6.09 (t, J = 7.2 Hz, 1H), 4.33 (s, 2H), 4.12 (d, J = 7.2 Hz, 2H), 3.93 (s, 3H). 13 C NMR (101 MHz, CDCl 3)δ166.73,143.59,140.41,130.15,130.11,128.01,126.33,52.34,48.35,26.94.HRMS(ESI):m / z calculated for[C 12 H 12 BrN 3 O 2 + -N 3 :267.0021,found:267.0031.

[0174] Example 51: Preparation of (Z)-((4-(4-azido-1-bromobut-2-en-2-yl)phenyl)ethynyl)trimethylsilane (5d)

[0175]

[0176] The target product 5d was prepared in the same manner as in Example 30, with the reaction time extended to 12 h. Colorless oily liquid, product yield 80%, Z / E = 97:3, 5d:5d' = 92:8 (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3 )δ7.49–7.45(m,2H),7.43–7.37(m,2H),6.02(t,J = 7.2Hz,1H),4.30(s,2H),4.09(d,J = 7.2Hz,2H),0.26(s,9H). 13 C NMR(101MHz,CDCl 3 )δ140.56,139.06,132.37,126.82,126.11,123.42,104.67,95.69,48.38,27.04,0.08.HRMS(ESI):m / z calculated for[C 15 H 18 BrN 3 Si + -N 3 :305.0361,found:305.0362.

[0177] Example 52: Preparation of (Z)-(4-(4-azido-1-bromobut-2-en-2-yl)phenoxy)(tert-butyl)dimethylsilane (5e)

[0178]

[0179] The preparation method of the target product 5e is the same as that of Example 30, and the reaction time is extended to 12 hours. It is a colorless oily liquid, the product yield is 77%, Z / E = 86:14, 5e:5e' > 98:2 (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3 )δ7.37–7.33(m,2H),6.85–6.81(m,2H),5.95(t,J = 7.3Hz,1H),4.31(s,2H),4.07(d,J = 7.3Hz,2H),0.99(s,9H),0.21(s,6H). 13 C NMR(101MHz,CDCl 3 )δ156.24,140.88,132.07,127.44,124.54,120.31,48.42,27.62,25.80,18.37,-4.24.HRMS(ESI):m / z calculatedfor[C 16 H 24 BrN 3 OSi + -N 3 :339.0780,found:339.0785.

[0180] Example 53: Preparation of (Z)-1-(4-azido-1-bromobut-2-en-2-yl)-4-chlorobenzene (5f)

[0181]

[0182] The preparation method of the target product 5f is the same as that of Example 30, and the reaction time is extended to 12 hours. It is a colorless oily liquid, the product yield is 68%, Z / E = 96:4, 5f:5f' = 90:10, (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3 )δ7.42–7.38(m,2H),7.37–7.33(m,2H),5.99(t,J = 7.2Hz,1H),4.29(s,2H),4.09(d,J = 7.2Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ140.26,137.64,134.55,129.01,127.68,126.68,48.32,27.17.HRMS(ESI):m / z calculated for[C10 H 9 BrClN 3 + -N 3 :242.9576,found:242.9577.

[0183] Example 54: Preparation of (Z)-1-(4-azido-1-bromobut-2-en-2-yl)-4-fluorobenzene (5 g)

[0184]

[0185] The preparation method of 5 g of the target product is the same as that of Example 30, and the reaction time is extended to 12 hours. Colorless oily liquid, product yield 78%, Z / E = 96:4, 5 g:5 g' = 96:4 (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 7.47–7.41 (m, 2H), 7.10–7.04 (m, 2H), 5.95 (t, J = 7.2 Hz, 1H), 4.30 (s, 2H), 4.08 (d, J = 7.2 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 162.96 (d, J = 248.1 Hz), 140.43, 135.33 (d, J = 3.3 Hz), 128.15 (d, J = 8.1 Hz), 126.19, 115.76 (d, J = 21.6 Hz), 48.32, 27.48. 19 F NMR (376 MHz, CDCl 3 ) δ -113.30 (ddd, J = 14.0, 8.7, 5.3 Hz). HRMS (ESI): m / z calculated for [C 10 H 9 BrFN 3 + -N 3 :226.9872,found:226.9873.

[0186] Example 55: Preparation of (Z)-1-(4-azido-1-bromobut-2-en-2-yl)-3,5-dimethylbenzene (5 h)

[0187]

[0188] The preparation method of the target product 5h is the same as that of Example 30, and the reaction time is extended to 12 hours. Colorless oily liquid, the product yield is 82%, Z / E = 94:6, 5h:5h' = 94:6 (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3 )δ7.08–7.06(m,2H),7.01–6.97(m,1H),5.97(t,J=7.3Hz,1H),4.32(s,2H),4.07(d,J=7.3Hz,2H),2.34(s,6H). 13 C NMR(101MHz,CDCl 3 )δ141.60,139.19,138.34,130.28,125.81,124.20,48.36,27.73,21.52.HRMS(ESI):m / z calculated for[C 12 H 14 BrN 3 + -N 3 :237.0278,found:237.0280.

[0189] Example 56: Preparation of (Z)-1-(4-azido-1-bromobut-2-en-2-yl)-4-(tert-butyl)benzene (5i)

[0190]

[0191] The preparation method of the target product 5i is the same as that of Example 30, and the reaction time is extended to 12 hours. Colorless oily liquid, the product yield is 85%, Z / E = 93:7, 5i:5i' = 96:4 (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz,CDCl 3 )δ7.44–7.38(m,4H),6.01(t,J=7.3Hz,1H),4.33(s,2H),4.08(d,J=7.3Hz,2H),1.33(s,9H). 13 C NMR(101MHz,CDCl 3 )δ151.74,141.03,136.07,125.92,125.75,125.40,48.36,34.75,31.39,27.48.HRMS(ESI):m / z calculated for[C 14 H 18 BrN 3+ -N 3 :265.0591, found:265.0592.

[0192] Example 57: Preparation of (Z)-4-(4-azido-1-bromobut-2-en-2-yl)-1,1'-biphenyl (5j)

[0193]

[0194] The preparation method of the target product 5j is the same as that of Example 30, and the reaction time is extended to 12 hours. Colorless oily liquid, the product yield is 74%, Z / E = 91:9, 5j:5j' = 96:4 (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz, CDCl 3 ) δ7.63–7.59(m, 4H), 7.57–7.53(m, 2H), 7.47–7.43(m, 2H), 7.39–7.34(m, 1H), 6.07(t, J = 7.2Hz, 1H), 4.37(s, 2H), 4.11(d, J = 7.2Hz, 2H). 13 C NMR(101MHz, CDCl 3 ) δ141.46, 140.86, 140.47, 137.94, 128.98, 127.70, 127.50, 127.16, 126.71, 126.07, 48.41, 27.35. HRMS(ESI): m / z calculated for [C 16 H 14 BrN 3 + -N 3 :285.0279, found:285.0280.

[0195] Example 58: Preparation of (Z)-1-(4-azido-1-bromobut-2-en-2-yl)cyclohex-1-ene (5k)

[0196]

[0197] The preparation method of the target product 5k is the same as that of Example 30, and the reaction time is extended to 12 hours. Colorless oily liquid, the product yield is 44%, Z / E = 86:14, 5k:5k'>98:2 (ethyl acetate / petroleum ether 1:20). 1 H NMR(400MHz, CDCl 3) δ 6.10 (t, J = 4.0 Hz, 1H), 5.71 (t, J = 7.3 Hz, 1H), 4.12 (s, 2H), 4.00 (d, J = 7.3 Hz, 2H), 2.25–2.15 (m, 4H), 1.75–1.67 (m, 2H), 1.65–1.57 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 141.65, 133.65, 127.15, 121.62, 48.36, 26.07, 26.04, 25.33, 22.79, 22.04. HRMS (ESI): m / z calculated for [C 10 H 14 BrN 3 -N 3 + : 213.0278, found: 213.0274.

[0198] Example 59: Preparation of (Z)-1-azido-3-(bromomethyl)dec-2-ene (5l)

[0199]

[0200] The target product 5l was prepared in the same manner as in Example 30, with the reaction time extended to 12 hours. Colorless oily liquid, product yield 85%, Z / E > 98:2, 5l:5l' > 98:2 (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 5.51 (t, J = 7.3 Hz, 1H), 3.96 (s, 2H), 3.87 (d, J = 7.3 Hz, 2H), 2.24 (t, J = 7.6 Hz, 2H), 1.52–1.40 (m, 2H), 1.34–1.26 (m, 8H), 0.89 (t, J = 6.5 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 142.51, 122.97, 47.67, 35.60, 31.89, 29.23, 29.21, 28.62, 27.78, 22.76, 14.20. HRMS (ESI): m / z calculated for [C 11 H 20 BrN 3 -N 3 + : 245.0779, found: 245.0758.

[0201] ​​Example 60: Preparation of (Z)-(4-azido-1-bromobut-2-en-2-yl)cyclohexane (5m)

[0202]

[0203] The preparation method of the target product 5m is the same as that of Example 30, and the reaction time is extended to 12 hours. Colorless oily liquid, the product yield is 78%, Z / E > 98:2, 5m:5m' > 98:2 (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ) δ 5.51 (t, J = 7.3 Hz, 1H), 3.97 (s, 2H), 3.91 (d, J = 7.3 Hz, 2H), 2.18–2.08 (m, 1H), 1.88–1.74 (m, 5H), 1.34–1.15 (m, 5H). 13 C NMR (101 MHz, CDCl 3 ) δ 147.51, 122.00, 47.74, 44.10, 32.68, 28.10, 26.70, 26.21. HRMS (ESI): m / z calculated for [C 10 H 16 BrN 3 -N 3 + : 257.0528, found: 257.0536.

[0204] Example 61: Preparation of

[0205] 1-((Z)-4-azido-1-bromobut-2-en-2-yl)-4-(((2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)benzene (5n)

[0206]

[0207] The preparation method of the target product 5n is the same as that of Example 30, and the reaction time is extended to 12 hours. Colorless oily liquid, the product yield is 76%, Z / E = 87:13, 5n:5n' > 98:2 (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ​)δ 7.42–7.36 (m, 1.15H), 7.13–7.07 (m, 0.85H), 6.93–6.87 (m, 2H), 5.95 (t, J = 7.3 Hz, 1H), 4.65 (s, 1H), 4.32 (s, 1.15H), 4.24 (s, 0.86H), 4.07 (d, J = 7.3 Hz, 1.14H), 3.78 (d, J = 7.2 Hz, 0.88H), 2.15–2.05 (m, 1H), 1.87–1.48 (m, 5H), 1.12–0.94 (m, 3H), 0.95–0.91 (m, 3H), 0.88–0.80 (m, 6H). 13 C NMR (101 MHz, CDCl 3 )δ 158.76, 140.93, 130.75, 127.51, 124.09, 115.69, 73.50, 48.44, 47.91, 37.78, 35.13, 29.43, 26.34, 24.97, 22.42, 21.18, 21.00. HRMS (ESI): m / z calculated for [C 20 H 28 BrN 3 O-N 3 + : 363.1323, found: 363.1327.

[0208] Example 62: Preparation of (Z)-4-(4-azido-1-bromobut-2-en-2-yl)phenyl 2-(2-fluoro-[1,1'-biphenyl]-4-yl)propanoate (5o)

[0209]

[0210] The target product 5o was prepared in the same manner as in Example 30, with the reaction time extended to 12 hours. A colorless oily liquid, the product yield was 82%, Z / E = 93:7, 5o:5o' > 98:2 (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ​) δ 7.58–7.53 (m, 2.97H), 7.49–7.41 (m, 7.28H), 7.40–7.35 (m, 1.5H), 7.28–7.21 (m, 3.02H), 7.12–7.04 (m, 2.94H), 5.97 (t, J = 7.3 Hz, 1.45H), 4.29 (s, 2H), 4.20 (s, 0.91H), 4.07 (d, J = 7.3 Hz, 2H), 4.01 (q, J = 7.2 Hz, 1.46H), 3.71 (d, J = 7.2 Hz, 0.9H), 1.66 (d, J = 7.1 Hz, 4.38H). 13 C NMR (101 MHz, CDCl 3 ) δ 172.45, 159.93 (d, J = 248.6 Hz), 150.93, 141.24 (d, J = 7.7 Hz), 140.45, 137.01, 135.49, 131.17 (d, J = 3.9 Hz), 129.77, 129.09 (d, J = 3.0 Hz), 128.61, 127.89, 127.46, 126.53, 123.71 (d, J = 3.4 Hz), 121.70, 115.46 (d, J = 23.9 Hz), 48.32, 45.30, 27.35, 18.52. HRMS (ESI): m / z calculated for [C 25 H 21 BrFN 3 O 2 -N 3 + : 451.0708, found: 451.0706.

[0211] Example 63: Preparation of (Z)-4-(4-azido-1-bromobut-2-en-2-yl)phenyl 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoate (5p)

[0212]

[0213] The target product 5p was prepared in the same manner as in Example 30, with the reaction time extended to 12 hours. Colorless oily liquid, product yield 84%, Z / E = 94:6, 5p:5p' > 98:2 (ethyl acetate / petroleum ether 1:20). 1 H NMR (400 MHz, CDCl 3 ​) δ 7.49–7.43 (m, 2H), 7.07–7.03 (m, 2H), 7.00 (d, J = 7.5 Hz, 1H), 6.67 (d, J = 7.5 Hz, 1H), 6.63 (s, 1H), 5.98 (t, J = 7.3 Hz, 1H), 4.30 (s, 2H), 4.08 (d, J = 7.3 Hz, 2H), 4.02–3.96 (m, 2H), 2.30 (s, 3H), 2.18 (s, 3H), 1.90–1.85 (m, 2H), 1.38 (s, 6H). 13 C NMR (101 MHz, CDCl 3 ) δ 176.34, 156.98, 151.26, 140.55, 136.74, 136.62, 130.49, 127.44, 126.38, 123.75, 121.90, 120.91, 112.09, 67.88, 48.34, 42.63, 37.28, 27.39, 25.41, 25.27, 21.55, 15.94. HRMS (ESI): m / z calculated for [C 25 H 28 BrN 3 O 3 -N 3 + : 457.1378, found: 457.1379.

[0214] Example 64: Preparation of (E)-(3-chlorobuta-1,3-dien-1-yl)benzene (6)

[0215]

[0216] First, the crude product 2a was prepared according to Example 1. Then, potassium carbonate (0.0553 g, 2.0 equiv) and acetonitrile (1 mL) were added to the crude product, and the mixture was reacted at 60 °C until the reaction was complete. It was quenched with H 2 O and extracted with DCM. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure using a rotary evaporator. The resulting crude product was purified by column chromatography (using PE as the eluent) to obtain the product 6 with a separation yield of 62%. This compound has been reported (Jose, B.; Patricia, M.; Fernando, A.; Carlos, V. Adv. Synth. Catal. 2006, 348, 347 - 353.).

[0217] Example 65: Preparation of (E)-(3,4-diazidobut-1-en-1-yl)benzene (7)​

[0218]

[0219] The crude product 2a was prepared according to Example 1, and then sodium azide (0.0390 g, 1.5 equiv), acetone (0.8 mL) and water (0.2 mL) were added to the crude product, and the mixture was reacted at 60 °C until the reaction was complete. H 2 O was quenched and extracted with DCM. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure using a rotary evaporator. The resulting crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:20) to obtain the product 7 with a separation yield of 65%. This compound has been reported (Shen, S.-J; Zhu, C.-L; Lu, D.-Fu; Xu, H. ACS Catal. 2018, 8, 4473 - 4482.).

[0220] Example 66: Preparation of (E)-(3,4-diazidobut-1-en-1-yl)benzene (8)

[0221]

[0222] Under an argon atmosphere, compound 4a (0.2521 g, 1.0 mmol, 1.0 equiv), morpholine (0.2610 g, 3.0 mmol), and methanol (2.5 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar, and the mixture was reacted at 25 °C until the reaction was complete. H 2 O was quenched and extracted with DCM. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure using a rotary evaporator. The crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:5) to obtain the compound 8 as a pale yellow oil with a separation yield of 73%. In addition, the by-product 12 was obtained with a separation yield of 18%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.41–7.37 (m, 2H), 7.36–7.31 (m, 2H), 7.29–7.24 (m, 1H), 6.65 (d, J = 15.8 Hz, 1H), 6.08 (dd, J = 15.8, 7.5 Hz, 1H), 4.29–4.20 (m, 1H), 3.73 (m, 4H), 2.65–2.56 (m, 3H), 2.50 (m, 3H). 13 C NMR (101 MHz, CDCl 3)δ136.00,133.62,128.75,128.29,126.72,125.41,66.97,63.04,61.53,54.02.HRMS(ESI):m / z calculated for C 14 H 19 N 4 O[M+H] + :259.1559,found:259.1557.

[0223] Example 67: Preparation of (E)-1-morpholino-4-phenylbut-3-en-2-amine (9)

[0224]

[0225] Under an argon atmosphere, activated zinc powder (0.0396 g, 0.6 mmol, 3.0 equiv), ammonium chloride (0.535 g, 1.0 mmol, 5.0 equiv), compound 8 (0.0517 g, 0.2 mmol, 1.0 equiv), ethanol (0.75 mL), and water (0.25 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar. The mixture was reacted at 25 °C until the reaction was complete, quenched with saturated sodium carbonate solution, and extracted with EA. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure using a rotary evaporator. The crude product was purified by column chromatography (methanol / dichloromethane 1:5) to give a pale yellow oil 9 with a separation yield of 88%. 1 H NMR(400MHz,CDCl 3 )δ7.39–7.34(m,2H),7.33–7.28(m,2H),7.26–7.20(m,1H),6.61(d,J=15.9Hz,1H),6.17(dd,J=15.9,6.9Hz,1H),3.82–3.63(m,5H),3.39(s,2H),2.66–2.54(m,2H),2.50–2.35(m,4H). 13 C NMR(101MHz,CDCl 3 )δ(ppm)136.71,131.52,130.04,128.70,127.83,126.52,67.10,64.24,53.93,50.53.HRMS(ESI):m / z calculated forC 14 H 21 N 2 O[M+H] +: 233.1654, found: 233.1652.

[0226] Example 68: Preparation of (E)-1-(1-bromo-4-phenylbut-3-en-2-yl)-4-phenyl-1H-1,2,3-triazole (10)

[0227]

[0228] Under an argon atmosphere, CuSO 4 ·5H 2 O (0.0050 g, 10 mol%), sodium ascorbate (0.0079 g, 20 mol%), compound 4a (0.0504 g, 0.2 mmol), phenylacetylene (0.0306 g, 0.3 mmol), tert-butanol (0.5 mL), water (0.5 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar, and the mixture was reacted at 25 °C until the reaction was complete. It was quenched with H 2 O and extracted with DCM. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure using a rotary evaporator. The crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:5) to obtain a pale yellow oil 10 with an isolated yield of 85%. 1 1H NMR (400 MHz, CDCl 3 ) δ 7.90 (s, 1H), 7.88–7.82 (m, 2H), 7.46–7.38 (m, 4H), 7.38–7.29 (m, 4H), 6.71 (d, J = 15.9 Hz, 1H), 6.50 (dd, J = 15.9, 7.7 Hz, 1H), 5.50 (td, J = 7.2, 5.2 Hz, 1H), 4.06 (dd, J = 10.8, 7.2 Hz, 1H), 3.94 (dd, J = 10.8, 5.2 Hz, 1H). 13 13C NMR (101 MHz, CDCl 3 ) δ 147.64, 136.30, 135.11, 130.51, 129.08, 128.97, 128.93, 128.38, 127.02, 125.88, 123.38, 119.43, 64.00, 33.88. HRMS (ESI): m / z calculated for C 18 18 17 11 3 BrN + [M+H]

[0229] Example 69: Preparation of (E)-2-azido-4-phenylbut-3-en-1-ol (11)

[0230]

[0231] Under an argon atmosphere, compound 4a (0.0504 g, 0.2 mmol), DMSO (0.8 mL), and H 2 O (0.2 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar, and the mixture was reacted at 80 °C until the reaction was complete. The reaction was quenched with H 2 O and extracted with EA, washed with water and saturated NaCl solution, dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure using a rotary evaporator. The crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:5) to obtain a pale yellow oil 11 with a separation yield of 77%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.43–7.39 (m, 2H), 7.37–7.32 (m, 2H), 7.31–7.26 (m, 1H), 6.73 (d, J = 15.9 Hz, 1H), 6.14 (dd, J = 15.9, 8.1 Hz, 1H), 4.25 (dddd, J = 8.1, 7.2, 4.4, 0.7 Hz, 1H), 3.73 (dd, J = 11.4, 4.4 Hz, 1H), 3.64 (dd, J = 11.4, 7.2 Hz, 1H), 1.99 (s, 1H). 13 C NMR (101 MHz, CDCl 3 ) δ 135.74, 135.46, 128.84, 128.60, 126.87, 123.02, 66.47, 65.12. HRMS (ESI): m / z calculated for C 10 H 12 N 3 O [M+H] + : 190.0980, found: 190.0976.

[0232] Example 70: Preparation of (E)-(3-azidobuta-1,3-dien-1-yl)benzene (12)

[0233]

[0234] Under an argon atmosphere, compound 4a (0.0504 g, 0.2 mmol), triethylamine (0.0607 g, 3.0 equiv), and tetrahydrofuran (1.0 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar, and the mixture was reacted at 25 °C until the reaction was complete. H 2 O was added to quench the reaction, and the mixture was extracted with DCM. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure using a rotary evaporator. The crude product was purified by column chromatography (using petroleum ether as the eluent) to give a pale yellow oil 12 in 85% isolated yield. This compound has been reported (Liu, Z.-H; Liao, P.-Q; Bi, X.-H. Org. Lett. 2014, 16, 3668 - 3671.).

[0235] Example 71: Preparation of (E)-2-azido-4-phenylbut-3-en-1-ol (7)

[0236]

[0237] Under an argon atmosphere, NaN 3 (0.0488 g, 1.5 equiv), 4a (0.1260 g, 0.5 mmol), acetone (2.0 mL), and H 2 O (0.4 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar, and the mixture was reacted at 60 °C until the reaction was complete. H 2 O was added to dilute the reaction mixture, and the mixture was extracted with EA. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure using a rotary evaporator. The crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:20) to give product 7 in 98% isolated yield. This compound has been reported.

[0238] Example 72: Preparation of (Z)-4-azido-2-phenylbut-2-en-1-ol (13)

[0239]

[0240] Under an argon atmosphere, 5a (0.0504 g, 0.2 mmol, Z / E = 90:10), DMSO (0.8 mL), and H 2 O (0.2 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar, and the mixture was reacted at 80 °C until the reaction was complete. H 2Quenched with O and extracted with EA, then washed with water and saturated NaCl solution, dried over anhydrous sodium sulfate for the combined organic phase, filtered, then concentrated under reduced pressure using a rotary evaporator, and the crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:5) to obtain the product 13 with a separation yield of 79% (Z / E = 31:69). 1 H NMR(400MHz,CDCl 3 )δ7.39–7.33(m,3H),7.19–7.15(m,2H),5.87(tt,J=7.4,1.6Hz,1H),4.36(s,2H),3.74(d,J=7.4Hz,2H),1.97(s,1H). 13 C NMR(101MHz,CDCl 3 )δ144.57,139.72,128.76,128.24,126.71,123.89,59.92,48.17.HRMS(ESI):m / z calculated for C 10 H 12 N 3 O[M+H] + :190.0980,found:190.0977.

[0241] Example 73: Preparation of (Z)-4-(4-azido-2-phenylbut-2-en-1-yl)morpholine (14)

[0242]

[0243] Under an argon atmosphere, potassium carbonate (0.0553 g, 2.0 equiv), 5a (0.0504 g, 0.2 mmol, Z / E = 90:10), morpholine (0.0522 g, 3.0 equiv), and DMF (1.0 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar, and the reaction mixture was placed at 40 °C until the reaction was complete. Add H 2 Quenched with O and extracted with EA, then washed with water and saturated NaCl solution, dried over anhydrous sodium sulfate for the combined organic phase, filtered, then concentrated under reduced pressure using a rotary evaporator, and the crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:5) to obtain the product 14 with a separation yield of 90% (Z / E = 75:25). 1 HNMR(400MHz,CDCl 3) δ 7.51–7.43 (m, 2H), 7.36–7.30 (m, 3H), 5.98 (t, J = 7.3 Hz, 1H), 4.12 (d, J = 7.3 Hz, 2H), 3.64 (t, J = 4.6 Hz, 4H), 3.39 (s, 2H), 2.45 (t, J = 4.6 Hz, 4H). 13 C NMR (101 MHz, CDCl 3 ) δ 141.86, 141.26, 128.34, 127.75, 126.70, 125.58, 67.03, 57.81, 53.47, 48.57. HRMS (ESI): m / z calculated for C 14 H 19 N 4 O [M + H] + : 259.1559, found: 259.1558.

[0244] Example 74: Preparation of (Z)-(4-azido-1-thiocyanatobut-2-en-2-yl)benzene (15)

[0245]

[0246] Under an argon atmosphere, sodium thiocyanate (0.0178 g, 1.1 equiv), 5a (0.0504 g, 0.2 mmol, Z / E = 90:10), acetone (1.0 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar, and the reaction mixture was placed at 25 °C until the reaction was complete. Add H 2 O to quench and extract with EA, then wash with water and saturated NaCl solution, dry the combined organic phases with anhydrous sodium sulfate, filter, then concentrate under reduced pressure using a rotary evaporator, and purify the crude product by column chromatography (ethyl acetate / petroleum ether 1:5) to obtain the product 15 with a separation yield of 82% (Z / E = 89:11, 15:15' = 95:5). 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.39 (m, 5H), 6.10 (t, J = 7.3 Hz, 1H), 4.11 (d, J = 7.3 Hz, 2H), 4.10 (s, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ (ppm) 138.43, 138.12, 128.97, 128.95, 127.83, 126.68, 111.43, 48.27, 33.29. HRMS (ESI): m / z calculated for [C11 H 10 N 4 S + -N 3 :188.0534,found:188.0531.

[0247] Example 75: Preparation of (Z)-2-((4-azido-2-phenylbut-2-en-1-yl)oxy)isoindoline-1,3-dione (16)

[0248]

[0249] Under an argon atmosphere, potassium carbonate (0.0553 g, 2.0 equiv), N-hydroxyphthalimide (0.0652 g, 2.0 equiv), 5a (0.0504 g, 0.2 mmol, Z / E = 90:10), and DMF (1.0 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar. The reaction mixture was stirred at 40 °C until the reaction was complete, quenched with H 2 O and extracted with EA, washed with water and saturated NaCl solution, dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure using a rotary evaporator. The crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:5) to give product 16 in a separated yield of 72% (72%, Z / E = 75:25, 16:16' = 93:7). 1 H NMR (400 MHz, CDCl 3 ) δ 7.85–7.81 (m, 2H), 7.77–7.73 (m, 2H), 7.66–7.61 (m, 2H), 7.41–7.34 (m, 3H), 6.25 (t, J = 7.4 Hz, 1H), 5.08 (s, 2H), 4.31 (d, J = 7.4 Hz, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 163.46, 139.55, 137.27, 134.69, 130.20, 128.93, 128.77, 128.59, 128.28, 126.36, 123.67, 74.42, 48.56. HRMS (ESI): m / z calculated for C 18 H 14 N 4 NaO 3 [M+Na] + : 357.0964, found: 357.0965.

[0250] Example 76: Preparation

[0251] (Z)-4-(4-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)-2-phenylbut-2-en-1-yl)morpholine(17)

[0252]

[0253] Under an argon atmosphere, CuSO 4 ·5H 2 O (0.0050 g, 10 mol%), sodium ascorbate (0.0079 g, 20 mol%), compound 14 (0.0517 g, 0.2 mmol, Z / E = 75:25), 4-ethynylbiphenyl (0.0306 g, 0.3 mmol), tert-butanol (0.5 mL), water (0.5 mL) were added to a 10 mL Schlenk tube equipped with a magnetic stir bar, and the reaction mixture was placed at 60 °C for reaction until the reaction was complete. The reaction was quenched with H 2 O and extracted with DCM. The combined organic phases were dried over anhydrous sodium sulfate, filtered, then concentrated under reduced pressure using a rotary evaporator, and the crude product was purified by column chromatography (ethyl acetate / petroleum ether 1:5) to obtain product 17 (Z / E = 75:25) with a separation yield of 88%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.91–7.85 (m, 2H), 7.67–7.58 (m, 4H), 7.46–7.39 (m, 4H), 7.37–7.25 (m, 4H), 7.24 (s, 1H), 6.09 (t, J = 7.0 Hz, 1H), 5.35 (d, J = 7.0 Hz, 2H), 3.70–3.63 (m, 4H), 3.50 (s, 2H), 2.58–2.43 (m, 4H). 13 C NMR (101 MHz, CDCl 3 ) δ 147.69, 141.55, 141.52, 140.86, 140.53, 129.66, 128.87, 128.45, 127.98, 127.54, 127.49, 126.98, 126.58, 126.11, 125.07, 119.46, 67.01, 58.20, 53.52, 48.56. HRMS (ESI): m / z calculated for C 28 H 29 N 4 O [M+H] +: 437.2341, found: 437.2346.

Claims

1. A method for preparing a bromochloride or bromoazide, characterized in that: Under an argon atmosphere, add the substrate 1,3-conjugated diene to a sealed tube, add an organic solvent, place the reaction mixture at 0 °C, sequentially add a nucleophile and a bromine positive reagent, stir the mixture at 0 °C until the reaction is complete; quench the reaction with a saturated aqueous sodium thiosulfate solution and extract with dichloromethane, dry the combined organic phases with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and obtain the bromochloride or bromoazide after separation and purification; The reaction route is as follows: In the formula, the substituent R 2 is an aryl group or a substituted aryl group; R 1 , R 3 , R 4 are H; R 5 、R 6 are each independently selected from hydrogen, alkyl or substituted alkyl, aryl or substituted aryl, halogen; The bromine positive reagent is NBS; When the nucleophile is TMSCl, the target product is bromochloride 2; when the nucleophile is TMSN 3 , the target product is bromoazide 4; The organic solvent is dry toluene.

2. The preparation method according to claim 1, characterized in that: During the reaction, the molar ratio of 1,3-conjugated diene to the nucleophile and the bromine positive reagent is 1:1.5:1.5.

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