A method for synthesizing N-amino-beta-amino acid compounds based on olefin and heteroarene nitrocarboxylation reaction

Abstract

The application discloses a method for synthesizing an amino acid compound based on olefin and heteroarene nitrogen carboxylation reaction N - amino group β - amino acid compound, belongs to the technical field of organic synthesis. The method comprises the following steps: mixing olefin or heteroarene, hydrazine, a photocatalyst and alkaline substances, then adding a solvent and an additive under a CO2 atmosphere to obtain a reaction liquid, and stirring the obtained reaction liquid under light irradiation at 0-100 DEG C for 0.1-100 hours to prepare N - amino group β - amino acid compound. The application realizes, for the first time, visible light catalysis of CO2 participating nitrogen carboxylation reaction of non-activated olefin and heteroarene. The system can efficiently complete single electron activation of CO2 under mild conditions, and can efficiently construct important N - amino group β - amino acid compound, and has wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a synthesis method based on the nitrogen carboxylation reaction of olefins and heteroaromatic hydrocarbons. N -amino- β - Methods for amino acid compounds. Background Technology

[0002] β Amino acids are a class of reaction intermediates widely used in synthesis, and they also play a crucial role in various fields such as medicine, food additives, and materials. For example, amino acids are derived from... β - Peptides composed of amino acids possess stable helical secondary structures, which can modify and improve material properties, as well as increase metabolic stability and resistance to proteolytic hydrolysis. Therefore, development β Efficient synthetic methods for amino acids and their derivatives are of great significance to organic chemistry and medicinal chemistry. From the perspective of retrosynthetic analysis, the nitrogen carboxylation reaction of alkenes is a key step in the synthesis of amino acids and their derivatives. β One of the simplest and most attractive strategies for amino acid skeletonization is the nitrogen carboxylation reaction, which utilizes inexpensive and readily available alkenes as substrates and can simultaneously introduce amino and carboxyl groups in one step, exhibiting excellent atom and step economy. Existing nitrogen carboxylation reactions are mainly limited to activated alkenes, while nitrogen carboxylation of non-activated alkenes requires the use of highly toxic C1 feedstocks such as CO or pre-prepared oxime oxalates. Therefore, there is an urgent need to develop a method for nitrogen carboxylation of non-activated alkenes utilizing abundant and green synthons. β -Methods for synthesizing amino acids.

[0003] On the other hand, carbon dioxide (CO2) is abundant, inexpensive, non-toxic, and renewable, making it an ideal C1 feedstock for sustainable chemistry. CO2-involved carboxylation reactions have become an efficient and practical synthetic strategy for constructing high-value carboxylic acid compounds. Therefore, CO2-involved olefin nitrogen carboxylation reactions are... β The preparation of amino acids offers a highly attractive synthetic route. However, CO2-involved nitrogen carboxylation reactions of inactive alkenes and heteroaromatics have not yet been reported. Summary of the Invention

[0004] To address the aforementioned shortcomings of existing technologies, the purpose of this invention is to provide a synthesis method based on the nitrogen carboxylation reaction of olefins and heteroaromatic hydrocarbons. N -amino- β - A method for synthesizing amino acid compounds to address the limitations of existing technologies using CO2 synthesis. β This method overcomes the limitations of substrates for amino acid products, and features mild reaction conditions, inexpensive and readily available raw materials, a wide range of substrates, and good chemical selectivity.

[0005] The technical solution of this invention to solve the above-mentioned technical problems is as follows: A method for synthesizing based on the nitrogen carboxylation reaction of olefins and heteroaromatics is provided. N -amino- β - A method for processing amino acid compounds, comprising the following steps: An olefin or heteroaromatic hydrocarbon, an acyl hydrazine, a photocatalyst, and an alkaline substance are mixed, and then a solvent and additives are added under a CO2 atmosphere to obtain a reaction solution. The resulting reaction solution is stirred under light irradiation at 0–100 °C for 0.1–100 hours to obtain the desired product. N -amino- β -Amino acid compounds; The general structural formula of the above-mentioned olefins is shown in formula (I):

[0006] Among them, R 1 R 2 R 3 and R 4 All are hydrogen, alkyl, aryl, heteroaryl, ester, amide, cyano, carbonyl, or heteroatoms protected by protecting groups; R 3 R 4 The two cases are represented by a dashed line, namely R. 3 and R 4 Connected or R 3 and R 4 Not connected, when R 3 With R 4 When the components are not connected, the compound is an acyclic alkene; when R... 3 and R 4 When the ends are connected, the compound is a cyclic intraolefin; The general structural formula of heteroaromatic hydrocarbons is shown in formula (II):

[0007] Wherein, X is a heteroatom or a heteroatom protected by a protecting group, and the heteroatom can be a nitrogen atom, an oxygen atom, or a sulfur atom; R 5 R 6 R 7 R 8 and R 9 All are hydrogen, alkyl, alkoxy, halogen, amide (Me2NOC-) or aryl (e.g. ); The general structural formula of acylhydrazide is shown in formula (III):

[0008] Among them, R 10 It is an alkyl or alkoxy group.

[0009] Furthermore, the structural formula of the olefin is shown below: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0010] Furthermore, the structural formula of heteroaromatic hydrocarbons is shown below: , , , , , , , , , , .

[0011] Furthermore, the structural formula of the acylhydrazide is shown below: , , .

[0012] Furthermore, the molar ratio of olefins or heteroaromatics, acyl hydrazides, photocatalysts, alkaline substances and additives is 1 : (0.1~10) : (0.001~1) : (0.1~10) : (0.1~10).

[0013] Furthermore, the photocatalyst is a DA-type photocatalyst or an organometallic photocatalyst.

[0014] Furthermore, the photocatalyst is fac -Ir(ppy)3、 fac -Ir(dF(ppy)3) and fac At least one of -Ir(dtbppy)3.

[0015] Furthermore, the alkaline substance is at least one of tert-butoxide, carbonate, fluoride, carboxylate, phosphate, and organic base.

[0016] Furthermore, tert-butoxide is a KO t Bu, NaO t Bu、LiO t Bu or Ca(O t Bu)2; carbonates are Cs2CO3, K2CO3, Na2CO3 or Li2CO3; fluorides are CsF, KF, NaF or LiF; phosphates are K3PO4, Na3PO4 or Li3PO4; carboxylates are CsOAc, KOAc, NaOAc, CsOPiv, NaOPiv or KOPiv; organic bases are DBU, TBD, DABCO, TMG, DBN, TMEDA, Cy2NEt, Cy2NMe, PMP, NBu3, NMe3 or NET3.

[0017] Furthermore, the additive is at least one of organic amines, formates, and silanes.

[0018] Furthermore, the organic amine is Et3N, i Pr2NEt, Me3N, Bu3N, Cy2NEt, Cy2NMe, TEOA, TMEDA, PMP, DBU, TBD, DABCO, TMG or DBN.

[0019] Furthermore, the formate is HCOOCs, HCOOK, HCOONa, HCOOLi, (HCOO)2Ca, (HCOO)2Zn, HCOONH4 or HCOONBu4.

[0020] Furthermore, the silanes are PMHS, Et3SiH, MeEt2SiH, and Me2EtSiH. i Pr3SiH, n Pr3SiH, n Hex3SiH, PhSiH3, Ph2SiH2, Ph3SiH, PhMe2SiH, Ph2MeSiH, BnMe2SiH, (MeO)3SiH, Me(MeO)2SiH, (EtO)3SiH, Me(EtO)2SiH, ( iPrO)3SiH, (Me3Si)3SiH, Me(Me3Si)2SiH or 1,4-di(dimethylsilyl)benzene.

[0021] Furthermore, the solvent is DMSO, NMP, DMF, or DMAc.

[0022] Furthermore, the reaction pressure is 0.1 to 30 times atmospheric pressure, the light source wavelength is 300 to 700 nm, and the light source power is 0.1 to 100 W.

[0023] The present invention can further modify the above. N -amino- β -Amino acid compounds are esterified and purified to obtain N -amino- β - Amino acid ester compounds.

[0024] The present invention has the following beneficial effects: (1) The method of the present invention uses olefins or heteroaromatic hydrocarbons as reaction substrates, carbon dioxide as carboxyl source and hydrazide as nitrogen source, and adds photocatalyst, base and additives to a visible light catalytic system to obtain the target carboxylic acid product. The method is simple to operate and the raw materials used are inexpensive and readily available.

[0025] (2) The synthesis method provided by the present invention exhibits excellent reactivity for a variety of olefin and heteroaromatic substrates, and has the advantages of mild reaction conditions, wide range of applicable substrates, excellent chemical selectivity and high product yield.

[0026] (3) This invention is the first to realize the nitrogen carboxylation reaction of non-activated olefins and heteroaromatics involving CO2 under visible light catalysis. This system can efficiently complete the single-electron activation of CO2 under mild conditions and can efficiently construct important... N -amino- β - Amino acid compounds have broad application prospects. Attached Figure Description

[0027] fac This is a reaction mechanism diagram of the present invention. Detailed Implementation

[0028] The examples given below are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise specified, conditions in the examples are performed under standard conditions or as recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0029] The reaction mechanism of this invention is as follows: fac As shown, firstly, the acylhydrazide generates a nitrogen anion intermediate under alkaline conditions, which then undergoes a single-electron transfer process with the excited-state photosensitizer to obtain the reduced-state Ir. IIPhotocatalysts and nitrogen radical intermediates. On the other hand, CO2 and reduced Ir. II The photocatalyst undergoes a single-electron transfer process, generating CO2 radical anion species and regenerating Ir. III The photocatalyst then triggers a CO2 radical anion to attack the double bond of an olefin or heteroaromatic hydrocarbon, generating a carboxylated alkyl radical intermediate. This intermediate undergoes a radical-radical cross-coupling process with a nitrogen radical intermediate, and finally, the target product is obtained after acidification.

[0030] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0031] Example 1: A synthesis based on the nitrogen carboxylation reaction of olefins and heteroaromatics N -amino- β The method for treating amino acid compounds, with the reaction formula shown below:

[0032] The specific synthesis process includes the following steps: After drying a 25 mL Schlenk reaction tube equipped with a stirrer under vacuum, a photocatalyst was added. fac -Ir(ppy)3 (0.001 mmol, 0.5 mol%) and hydrazide (0.6 mmol, 3.0 equivalents) were then placed in a glove box and KO was added. tBu (0.8 mmol, 4.0 equivalent) was used as the base. The reaction tube was then sealed with a stopcock, removed from the glove box, and purged three times under a double-row CO2 atmosphere. After purging, olefins or heteroaromatics (0.2 mmol, 1.0 equivalent), additive Et3N (0.1 mmol, 0.5 equivalent), and ultra-dry DMSO (4.0 mL) were added sequentially under a CO2 stream. The reaction tube was immediately sealed after addition and fixed in an oil bath (preheated to 50 °C). The stirrer was set to 600 r / min, and a 30 W blue LED lamp (wavelength approximately 420-480 nm) was used to irradiate the reaction mixture at a distance of 1 cm. A fan was used for cooling to maintain the reaction temperature at 50 °C. After stirring for 24 hours, 2 mL of ethyl acetate was added to dilute the reaction mixture, followed by 2 mL of 2... N hydrochloric acid was added and stirred for 3 minutes. The reaction mixture was then extracted with ethyl acetate until no product remained as monitored by thin-layer chromatography. The organic phases were combined and the residual solvent was completely removed by rotary evaporation. The crude product was purified by column chromatography under the following conditions: washing with a mixed solvent of petroleum ether:ethyl acetate:glacial acetic acid = 4:1:0~1:1:0.6% (v:v) to obtain the target carboxylic acid product. The carboxylic acid product can also be further esterified. Specifically, the carboxylic acid product was dissolved in 2 mL of methanol and 2 mL of diethyl ether, and trimethylsilyl diazomethane (1 mmol, 5 equivalents, 2 N n-hexane solution) was added dropwise at 0 °C. After the addition was complete, the mixture was immediately stirred at room temperature for 3 hours. The residual solvent was then completely removed by rotary evaporation. The crude product was purified by column chromatography under the following conditions: washing with a mixed solvent of petroleum ether:ethyl acetate = 10:1~3:1 (v:v) to obtain the target carboxylic acid ester product. The specific reaction products, corresponding product yields, and selectivity results are as follows:

[0033]

[0034]

[0035]

[0036]

[0037]

[0038]

[0039]

[0040]

[0041]

[0042]

[0043]

[0044] .

[0045] Note: All results above represent separation yields; diastereomer ratios (dr) and regiomeric ratios (rr) were determined by 1H NMR spectroscopy; data marked 'a' in the upper right corner of the separation yield represents the separation yield of the carboxylic acid product; data marked 'b' in the upper right corner of the separation yield represents the separation yield of azididine (0.6 mmol, 3.0 equivalent) and KO... t Data for when Bu (0.8 mmol, 4.0 equivalents) is replaced with hydrazide (0.4 mmol, 2.0 equivalents) and Cs2CO3 (0.6 mmol, 3.0 equivalents) while keeping other reaction conditions unchanged; data marked with 'c' in the upper right corner of the separation yield is data when beta-pinene is used as the substrate; data marked with 'd' in the upper right corner of the separation yield is data when diallyl ether is used as the substrate.

[0046] Example 2: A synthesis based on the nitrogen carboxylation reaction of olefins and heteroaromatics N -amino- β - The method for synthesizing amino acid compounds, when the substrate is ethylene, has the following synthetic reaction formula:

[0047] The specific synthesis process includes the following steps: After drying a 25 mL Schlenk reaction tube equipped with a stirrer under vacuum, a photocatalyst was added. fac -Ir(ppy)3 (0.001 mmol, 0.25 mol%) and hydrazide (0.4 mmol, 1.0 equivalent) were then placed in a glove box and KO was added. tBu (1.0 mmol, 2.5 equivalents) was used as the base. Note that the Schlenk tube can be sealed with a rubber stopper. After sealing, the tube was removed from the glove box and purged three times under a double-row CO2 atmosphere. After purging, Et3N (0.1 mmol, 0.5 equivalents) and ultra-dry DMSO (4.0 mL) were added sequentially under a CO2 stream. After the addition was complete, 20 mL of ethylene gas was injected through the rubber stopper using a syringe, and the tube was immediately and carefully sealed with black tape. The reaction tube was then fixed in an oil bath (preheated to 50 °C). The stirrer was set to 600 r / min, and a 30 W blue LED lamp (wavelength approximately 420-480 nm) was used to irradiate the reaction mixture at a distance of 1 cm. A fan was used for cooling to maintain the reaction temperature at 50 °C. After stirring for 24 hours, 2 mL of ethyl acetate was added to dilute the reaction mixture, followed by 2 mL of 2... N hydrochloric acid was added and stirred for 3 minutes. The reaction mixture was then extracted with ethyl acetate until no product remained as monitored by thin-layer chromatography. The organic phases were combined and the residual solvent was completely removed by rotary evaporation. The crude product was purified by column chromatography under the following conditions: washing with a mixed solvent of petroleum ether:ethyl acetate:glacial acetic acid = 4:1:0~1:1:0.6% (v:v) to obtain the target carboxylic acid product. The carboxylic acid product can also be further esterified. Specifically, the carboxylic acid product was dissolved in 2 mL of methanol and 2 mL of diethyl ether, and trimethylsilyl diazomethane (1 mmol, 5 equivalents, 2 N n-hexane solution) was added dropwise at 0 °C. After the addition was complete, the mixture was immediately stirred at room temperature for 3 hours. The residual solvent was then completely removed by rotary evaporation. The crude product was purified by column chromatography under the following conditions: washing with a mixed solvent of petroleum ether:ethyl acetate = 10:1~3:1 (v:v) to obtain the target carboxylic acid ester product. The specific reaction products, corresponding product yields, and selectivity results are as follows: .

[0048] The experimental results above show that various substituted unactivated alkenes, ethylene, activated alkenes, and heteroaromatics can all yield the target product in good yields. Furthermore, this reaction system is compatible with a wide range of functional groups, including alkenyl, protected hydroxyl, protected amino, heterocyclic, ester, aryl, cyano, (thio)ether, ketone carbonyl, amide, halogen, and silyl groups, among others. In addition, the system is also compatible with functional groups derived from natural products, including methasalone, pregnenolone, gemfibrozil, and borneol, etc.

[0049] Based on the above description, it is clear to those skilled in the art that all reaction substrates that meet the above reaction mechanism conditions are suitable. Specifically, when the reaction substrate is replaced with other reaction substrates described in this application, the remaining components and reaction conditions remain unchanged, and the final yield is not significantly different from the yield of the technical solution in this application. Therefore, the applicant will not provide separate examples for further explanation.

[0050] Example 3: While keeping the operation process unchanged in Example 1, 3-buten-1-ol protected by pivaloyl was used as the reaction substrate. The effects of various factors on the reaction yield were investigated by changing the reaction conditions. The reaction conditions were: 3-buten-1-ol protected by pivaloyl (0.2 mmol, 1 equivalent). fac fac fac fac fac fac fac fac fac fac fac fac -Ir(ppy)3 (0.001 mmol, 0.5 mol%), acylhydrazide (0.6 mmol, 3 equivalents), KO t Bu (0.8 mmol, 4 equivalents), Et3N (0.1 mmol, 0.5 equivalents), and ultra-dry solvent DMSO (4 mL) were used. Specific experimental results are shown in Table 1 below. The reaction process is as follows:

[0051] Table 1. Product yields under different reaction conditions

[0052] The data in the table above show that the yield is as high as 83% under the reaction conditions of this invention. A series of controlled experiments indicate that light, photocatalyst, CO2, and base play indispensable roles in the reaction; the absence of any one of these will result in either no product or only trace amounts. Adding a small amount of triethylamine to the system significantly improves the reaction efficiency, possibly because Et3N promotes the generation of CO2 radical anions. When using other types of photocatalysts and organic solvents, the product yield decreases. Furthermore, changing to other bases or reducing additives also leads to a decrease in product yield.

[0053] The product obtained by this invention was characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The NMR and MS data were consistent with the obtained product. Specific characterization data are as follows: 1-(1-Methoxy-1-oxo-5-(neovaleroxy)pentan-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3a)

[0054] Yield: 65.1 mg; Yield: 83%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1H NMR (400 MHz, CDCl3) δ 6.76 – 6.42 (m, 1H), 4.79 – 4.56 (m, 1H), 4.31 – 4.04 (m, 6H), 3.67 (s, 3H), 2.93 – 2.38 (m, 2H), 2.00 – 1.68 (m, 2H),1.34 – 1.24 (m, 6H), 1.21 (s, 9H). 13 C NMR (101 MHz, DMSO-) d 6) δ 177.3, 170.8,156.8, 155.2, 61.8, 61.5, 60.9, 60.4, 51.3, 50.6, 38.2, 38.1, 36.7, 30.5,30.0, 26.9, 26.8, 14.4.HRMS (ESI+)[M+Na] + Calculated m / z for [C 17 H 30 [N2NaO8] + :413.1894, found: 413.1894. 3-(1,2-Diethoxycarbonylhydrazyl)-5-(pivaloyloxy)valerate (3a')

[0055] Yield: 67.5 mg; Yield: 90%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, DMSO-) d 6)δ 12.22 (s, 1H), 9.31 – 8.68 (m, 1H), 4.72 –4.47 (m, 1H), 4.24 – 3.83 (m, 6H), 2.66 – 2.17 (m, 2H), 1.85 – 1.53 (m, 2H),1.28 – 1.07 (m, 15H). 13 C NMR (101 MHz, DMSO-) d 6) δ 177.4, 172.0, 157.2, 155.3,61.8, 61.5, 60.9, 60.5, 51.5, 38.2, 37.3, 30.0, 26.90, 26.86, 14.4.HRMS(ESI-)[MH] - Calculated m / z for [C16 H 27 N2O8] - : 375.1773, found: 375.1773. 1-(1-methoxy-1-oxo-5-(pivaloyloxy)pent-3-yl)hydrazine-1,2-dicarboxylic acid ditert-butyl ester (3b)

[0056] Yield: 69.4 mg; Yield: 78%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.46 – 6.01 (m, 1H), 4.79 – 4.43 (m, 1H), 4.33 – 3.99 (m, 2H), 3.66 (s, 3H), 2.90 – 2.35 (m, 2H), 1.97 – 1.74 (m, 2H),1.56 – 1.38 (m, 18H), 1.21 (s, 9H). 13 C NMR (101 MHz, DMSO-) d 6) δ 177.7, 171.3,156.2, 154.7, 80.7, 80.2, 79.9, 61.6, 60.8, 60.2, 55.3, 51.8, 38.6, 37.4,31.0, 30.4, 28.4, 28.3, 27.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 21 H 38 [N2NaO8] + : 469.2520, found: 469.2518. Methyl 3-(1,2-di-pivaloylhydrazino)-5-(pivaloyloxy)valerate (3c)

[0057] Yield: 41.4 mg; Yield: 50%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1HNMR(400 MHz, CDCl3) δ 8.81 – 8.25 (m, 1H), 4.72 – 3.98 (m, 3H), 3.67(s, 3H), 3.43 – 2.39 (m, 2H), 2.28 – 1.79 (m, 2H), 1.29 (s, 9H), 1.20 (s,18H). 13 C NMR (101 MHz, DMSO-) d 6) δ 178.7, 178.0, 177.8, 171.8, 61.9, 61.3, 54.6,52.7, 51.8, 38.6, 38.4, 37.9, 37.4, 31.3, 30.4, 28.3, 27.4, 27.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 21 H 38 [N2NaO6] + : 437.2622, found: 437.2618. 1-(1-Methoxy-1,6-dioxo-6-phenylaminohexyl-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3d)

[0058] Yield: 64.0 mg; Yield: 80%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 HNMR(400 MHz, CDCl3) δ 9.01 – 8.46 (m, 1H), 7.65 – 7.48 (m, 2H), 7.31– 7.21 (m, 2H), 7.05 (t, J = 7.4 Hz, 1H), 4.90 – 4.45 (m, 1H), 4.34 – 3.79(m, 4H), 3.65 (s, 3H), 2.97 – 2.24 (m, 4H), 2.21 – 1.54 (m, 2H), 1.53 – 0.99(m, 6H). 13 C NMR (101 MHz, DMSO-) d6) δ 170.9, 170.8, 157.0, 156.7, 155.4, 139.4,128.6, 122.9, 119.0, 61.8, 61.5, 60.9, 54.9, 54.1, 53.7, 51.4, 36.9, 33.1,32.8, 27.2, 26.9, 14.5, 14.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 19 H 27 [N3NaO7] + : 432.1741, found: 432.1741. 1-(4-methoxy-4-oxo-1-(2-oxopyrrolidone-1-yl)but-2-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3e)

[0059] Yield: 61.1 mg; Yield: 85%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 HNMR (400 MHz, CDCl3) δ 7.69 – 7.32 (m, 1H), 4.95 – 4.83 (m, 1H), 4.27 – 4.05 (m, 4H), 3.92 – 3.49 (m, 5H), 3.43 – 3.25 (m, 1H), 3.01 – 2.66 (m,2H), 2.48 – 2.14 (m, 3H), 2.10 – 1.91 (m, 2H), 1.30 – 1.20 (m, 6H). 13 C NMR (101MHz, DMSO-) d 6) δ 175.6, 170.6, 155.9, 155.7, 61.8, 61.1, 51.4, 50.7, 50.3,47.2, 42.9, 33.7, 33.4, 30.4, 30.2, 17.6, 14.4.HRMS (ESI+)[M+Na] + calculated m / z for [C 15 H 25 [NNaO7] + : 382.1585, found: 382.1594. 1-(1-(tert-Butoxycarbonylamino)-4-methoxy-4-oxobut-2-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3f)

[0060] Yield: 56.1 mg; Yield: 72%; Regioisomer ratio: 16:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 4.81 – 4.51 (m, 1H), 4.37 – 4.04 (m, 4H), 3.67 (s, 3H), 3.55 – 3.20 (m, 1H), 3.14 – 2.83 (m, 1H), 2.83 – 2.49 (m, 1H), 2.48 – 2.29 (m, 1H), 1.49 – 1.37 (m, 9H), 1.33 – 1.23 (m, 6H). 13 C NMR (101 MHz, DMSO- d 6) δ 171.2, 156.8, 156.2, 155.8, 78.7, 62.4, 62.2, 61.6, 53.8, 51.9,40.8, 34.3, 28.5, 14.8.HRMS (ESI+)[M+Na] + Calculated m / z for [C 16 H 29 [N3NaO8] + :414.1847, found: 414.1851. 1-(1,6-dimethoxy-1,6-dioxohexyl-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3g)

[0061] Yield: 52 mg; Yield: 75%; Regioisomer ratio: 12:1; Appearance: Pale yellow oily liquid; 1 HNMR(400 MHz, CDCl3) δ 6.95 – 6.36 (m, 1H), 4.80 – 4.45 (m, 1H), 4.30 – 4.04 (m, 4H), 3.67 (s, 6H), 2.88 – 2.26 (m, 4H), 1.94 – 1.64 (m, 2H), 1.34– 1.19 (m, 6H). 13 C NMR (101 MHz, DMSO-)d 6) δ 172.8, 170.8, 157.0, 155.4, 61.7,61.5, 60.9, 53.2, 51.3, 51.2, 36.7, 29.7, 26.8, 26.6, 26.3, 24.0, 14.4.HRMS(ESI+)[M+Na] + Calculated m / z for [C 14 H 24 [N2NaO8] + : 371.1425, found: 371.1430. 1-(1-methoxy-1-oxo-6-((2,2,3,3-tetramethylcyclopropane-1-carbonyl)oxy)hex-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3h)

[0062] Yield: 75.2 mg; Yield: 87%; Regioisomer ratio: 16:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.68 – 6.47 (m, 1H), 4.63 – 4.46 (m, 1H), 4.24 – 4.15 (m, 4H), 4.03 (t, J = 6.4 Hz, 2H), 3.66 (s, 3H), 2.79 – 2.38 (m,2H), 1.98 – 1.38 (m, 5H), 1.30 – 1.23 (m, 12H), 1.20 – 1.17 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 171.2, 170.9, 156.8, 155.4, 63.0, 61.7, 61.4, 60.8,51.3, 36.9, 34.8, 29.18, 29.16, 24.8, 23.1, 16.4, 14.5, 14.4.HRMS (ESI+)[M+Na] + Calculated m / z for [C 21 H 36 [N2NaO8] + : 467.2364, found: 467.2372. 1-(1-methoxy-5-((1-methyl-1H-pyrrole-2-carbonyl)oxy)-1-oxopentan-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3i)

[0063] Yield: 48 mg; Yield: 58%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.02 – 6.84 (m, 1H), 6.83 – 6.73 (m, 1H), 6.73 – 6.40 (m, 1H), 6.21 – 5.98 (m, 1H), 4.82 – 4.68 (m, 1H), 4.48 – 4.27(m, 2H), 4.25 – 4.07 (m, 4H), 3.92 (s, 2.6H), 3.85 (s, 0.4H), 3.66 (s, 3H), 2.90 – 2.39 (m, 2H), 2.08 – 1.82 (m, 2H), 1.30 – 1.20 (m, 6H). 13 C NMR (101 MHz, DMSO- d 6) δ 170.8, 160.4, 157.3, 155.3, 130.2, 121.9, 117.5, 107.6, 61.7,61.5, 60.9, 51.7, 51.4, 36.6, 36.4, 30.3, 14.4.HRMS (ESI+)[M+Na] + calculated m / z for [C 18 H 27 [N3NaO8] + : 436.1690, found: 436.1691. 1-(1-(cyclohexyl-3-en-1-yl)-3-methoxy-3-oxopropyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3j)

[0064] Yield: 35.4 mg; Yield: 52%; Regioisomer ratio: >20:1; Diastereomer ratio: 1:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, DMSO-) d6. A mixture of two diastereomers) δ 9.31 – 8.61 (m, 1H), 5.71 – 5.52 (m, 2H), 4.50 – 4.17 (m, 1H), 4.16 – 3.93 (m, 4H), 3.61 – 3.52 (m, 3H), 2.65 – 2.51 (m, 2H), 2.21 – 1.77 (m, 4H), 1.77 – 1.48 (m, 3H), 1.22 – 1.11 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6. A mixture of two diastereomers) δ 171.9, 171.8, 157.5, 155.9, 127.5, 126.7, 62.0, 61.8, 61.2, 59.1, 51.7, 36.3, 34.7, 28.4, 25.3, 14.9. HRMS (ESI+) [M+Na] + Calculated m / z for [C 16 H 26 [N2NaO6] + 365.1683, found: 365.1682. 1-(1-Methoxy-1-oxo-5-phenylpentan-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3k)

[0065] Yield: 52 mg; Yield: 71%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.30 – 7.15 (m, 5H), 6.58 – 6.24 (m, 1H), 4.69 – 4.47 (m, 1H), 4.26 – 4.12 (m, 4H), 3.65 (s, 3H), 3.01 – 2.80 (m, 1H), 2.76 – 2.55 (m, 2H), 2.49 – 2.39 (m, 1H), 1.98 – 1.68 (m, 2H), 1.30 – 1.23 (m, 6H). 13 C NMR (101 MHz, DMSO-) d6) δ 171.4, 157.6, 157.4, 155.9, 142.6, 142.1,128.8, 128.6, 126.1, 62.1, 61.9, 61.3, 54.4, 53.9, 51.8, 37.3, 34.1, 32.1,14.9, 14.8.HRMS (ESI+)[M+Na] + Calculated m / z for [C 18 H 26 [N2NaO6] + 389.1683, found: 389.1678. 1-(1-Methoxy-1-oxotridecane-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3l)

[0066] Yield: 47 mg; Yield: 58%; Regioisomer ratio: 13:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.71 – 6.13 (m, 1H), 4.64 – 4.39 (m, 1H), 4.29 – 4.07 (m, 4H), 3.66 (s, 3H), 2.79 – 2.34 (m, 2H), 1.64 – 1.18 (m, 24H),0.88 (t, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, DMSO-) d 6) δ 171.1, 155.4, 61.7, 61.3,60.7, 51.3, 37.0, 31.3, 29.03, 28.95, 28.7, 25.3, 22.1, 14.4, 13.9.HRMS (ESI+)[M+Na] + Calculated m / z for [C 20 H 38 [N2NaO6] + : 425.2622, found: 425.2617. 1-(3-cyano-1-(2-methoxy-2-oxoethyl)cyclobutyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3m)

[0067] Yield: 56 mg; Yield: 86%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.04 – 6.54 (m, 1H), 4.33 – 4.05 (m, 4H), 3.69 (s, 3H), 3.47 – 3.10 (m, 2H), 3.11 – 2.97 (m, 1H), 2.97 – 2.76 (m, 2H), 2.60 – 2.24 (m, 2H), 1.33 – 1.22 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 170.6,157.2, 154.7, 123.2, 62.1, 61.5, 52.0, 34.1, 15.5, 14.9, 14.7.HRMS (ESI+)[M+H] + Calculated m / z for [C 14 H 22 N3O6] + : 328.1503, found: 328.1503. 1-(1-(tert-Butoxycarbonyl)-4-(2-methoxy-2-oxoethyl)piperidin-4-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3n)

[0068] Yield: 61 mg; Yield: 71%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR(400 MHz, CDCl3) δ 6.91 – 6.72 (m, 1H), 4.27 – 4.10 (m, 4H), 3.67 (s, 3H), 3.55 – 3.48 (m, 2H), 3.41 – 3.27 (m, 2H), 2.62 – 2.40 (m, 2H),2.16 – 2.06 (m, 1H), 1.93 – 1.76 (m, 2H), 1.59 – 1.53 (m, 1H), 1.44 (s, 9H),1.33 – 1.25 (m, 6H). 13 C NMR (101 MHz, DMSO-) d6) δ 170.7, 157.1, 155.1, 154.0,78.6, 61.3, 61.0, 60.9, 59.7, 51.4, 39.9, 32.9, 32.0, 28.0, 20.7, 14.5,14.2.HRMS (ESI+)[M+Na] + Calculated m / z for [C 19 H 33 [N3NaO8] + : 454.2160, found:454.2160. 1-(4-(2-methoxy-2-oxoethyl)tetrahydro-2H-pyran-4-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3o)

[0069] Yield: 35 mg; Yield: 52%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.91 – 6.64 (m, 1H), 4.30 – 4.07 (m, 4H), 4.03 – 3.69 (m, 2H), 3.67 (s, 3H), 3.65 – 3.57 (m, 2H), 3.37 (d, J = 16.3 Hz,1H), 2.62 – 2.42 (m, 2H), 2.18 – 1.95 (m, 2H), 1.74 – 1.62 (m, 1H), 1.31 –1.22 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 170.7, 157.0, 155.1, 63.0, 62.7,61.2, 60.9, 60.3, 51.4, 34.0, 32.9, 14.5, 14.3.HRMS (ESI+)[M+Na] + calculated m / z for [C 14 H 24 [N2NaO7] + : 335.1476, found: 335.1473. 1-(7-(2-methoxy-2-oxoethyl)-6,7,8,9-tetrahydro-5H-benzo[7]cycloheptene-7-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3p)

[0070] Yield: 46 mg; Yield: 58%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR(400 MHz, CDCl3) δ 7.13 – 7.01 (m, 4H), 6.99 – 6.82 (m, 1H), 4.33 – 4.02 (m, 4H), 3.66 (s, 3H), 3.54 – 3.21 (m, 2H), 3.18 – 2.91 (m, 2H), 2.64 – 2.49 (m, 2H), 2.49 – 2.28 (m, 2H), 1.77 – 1.47 (m, 2H), 1.33 – 1.22(m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 171.0, 157.2, 155.3, 142.5, 142.3, 128.5,128.3, 125.93, 125.91, 66.5, 61.3, 60.9, 51.3, 34.8, 34.4, 29.4, 28.8, 26.3,14.6, 14.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 20 H 28 [N2NaO6] + : 415.1840, found: 415.1840. 1-(2-Benzyl-4-methoxy-4-oxo-1-phenylbut-2-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3q)

[0071] Yield: 52 mg; Yield: 59%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 HNMR (400 MHz, CDCl3) δ 7.36 – 7.19 (m, 8H), 7.21 – 7.13 (m, 2H), 5.87 – 5.05 (m, 1H), 4.37 – 3.58 (m, 9H), 3.43 – 3.11 (m, 2H), 2.64 (s, 2H), 1.35– 1.15 (m, 6H). 13C NMR (101 MHz, DMSO-) d 6) δ 171.2, 157.0, 155.7, 137.7, 137.4,131.2, 131.1, 128.5, 128.4, 126.85, 126.77, 67.6, 61.6, 61.1, 51.4, 38.2,15.0, 14.7.HRMS (ESI+)[M+Na] + Calculated m / z for [C 24 H 30 [N2NaO6] + : 465.1996, found: 465.1992. 1-tert-butyl-3-methyl-4-(1,2-bisethoxycarbonylhydrazyl)pyrrolidine-1,3-dicarboxylic acid ester (3r)

[0072] Yield: 48 mg; Yield: 60%; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.71 – 6.41 (m, 1H), 5.10 – 4.88 (m, 1H), 4.29 – 4.13 (m, 4H), 3.81 – 3.62 (m, 5H), 3.59 – 3.44 (m, 1H), 3.43 – 3.13(m, 2H), 1.45 (s, 9H), 1.30 – 1.25 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 172.1,157.2, 155.3, 153.6, 79.2, 62.4, 61.5, 52.5, 47.2, 46.8, 45.5, 28.5, 14.9,14.8.HRMS (ESI+)[M+Na] + Calculated m / z for [C 17 H 29 [N3NaO8] + : 426.1847, found:426.1846. Trimethyl(1R,2S,3R,4S,5R)-6-(1,2-bis(ethoxycarbonyl)hydrazino)bicyclo[2.2.1]heptane-2,3,5-tricarboxylic acid ester (3S)

[0073] Yield: 68 mg; Yield: 76%; Diastereomer ratio: 1:1; Appearance: Pale yellow oily liquid; 1 ¹H NMR (400 MHz, CDCl₃, mixture of two diastereomers) δ 6.73 – 6.32 (m, 1H), 4.57 – 4.27 (m, 1H), 4.26 – 4.08 (m, 4H), 3.79 – 3.58 (m, 9H), 3.37 – 3.16 (m, 1H), 3.11 – 2.53 (m, 4H), 2.46 – 2.10 (m, 1H), 1.71 – 1.50 (m, 1H), 1.32 – 1.22 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6. A mixture of two diastereomers) δ 173.5, 173.3, 173.1, 172.4, 172.1, 171.1, 157.3, 155.5, 61.7, 61.1, 59.8, 52.2, 52.07, 52.05, 52.0, 51.9, 51.5, 51.4, 47.9, 47.6, 47.2, 47.1, 45.0, 44.8, 43.2, 42.0, 36.4, 20.7, 14.41, 14.37. HRMS (ESI+) [M+Na] + calculated m / z for [C 19 H 28 N2NaO 10 ] + : 467.1636, found: 467.1632. 1-(5-(5-((3,5-dimethylphenoxy)methyl)-2-oxooxazolidine-3-yl)-1-methoxy-1-oxopentan-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3t)

[0074] Yield: 79 mg; Yield: 78%; Regioisomer ratio: 19:1; Diastereomer ratio: 1.1:1; Appearance: Pale yellow oily liquid; 1¹H NMR (400 MHz, CDCl₃, mixture of two diastereomers) δ 7.21 – 6.75 (m, 1H), 6.62 (s, 1H), 6.55 – 6.48 (m, 2H), 4.87 – 4.74 (m, 1H), 4.58 – 4.42 (m, 1H), 4.24 – 4.05 (m, 6H), 3.81 – 3.70 (m, 1H), 3.64 (s, 3H), 3.60 – 3.30 (m, 3H), 2.84 – 2.43 (m, 2H), 2.27 (s, 6H), 1.96 – 1.68 (m, 2H), 1.30 – 1.19 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6. A mixture of two diastereomers) δ 170.9, 158.24, 158.21, 157.0, 155.4, 138.7, 122.63, 122.58, 112.3, 71.0, 68.3, 61.9, 61.6, 60.9, 54.9, 51.4, 45.5, 36.5, 29.3, 21.0, 14.4, 14.3. HRMS (ESI+) [M+Na] + Calculated m / z for [C 24 H 35 [N3NaO9] + : 532.2266, found: 532.2268. 1-(6-(((3S,8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecano-1H-cyclopenta[a]phenanthrene-3-yl)oxy)-1-methoxy-1,6-dioxohexyl-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3u)

[0075] Yield: 68 mg; Yield: 54%; Regioisomer ratio: 12:1; Diastereomer ratio: 1:1; Appearance: Pale yellow oily liquid; 1¹H NMR (400 MHz, CDCl₃, mixture of two diastereomers) δ 6.98 – 6.29 (m, 1H), 5.45 – 5.32 (m, 1H), 4.72 – 4.46 (m, 2H), 4.32 – 3.98 (m, 4H), 3.67 (s, 3H), 2.83 – 2.24 (m, 7H), 2.24 – 2.15 (m, 1H), 2.13 (s, 3H), 2.09 – 1.95 (m, 2H), 1.93 – 1.77 (m, 3H), 1.78 – 1.39 (m, 9H), 1.37 – 1.07 (m, 10H), 1.01 (s, 3H), 0.63 (s, 3H). 13 C NMR (101 MHz, DMSO-) d 6. A mixture of two diastereomers) δ 208.8, 172.3, 171.2, 157.5, 157.3, 155.8, 140.0, 122.4, 73.5, 63.0, 62.2, 61.9, 61.3, 56.5, 51.8, 49.8, 43.7, 38.4, 38.1, 37.0, 36.6, 31.8, 31.7, 31.6, 27.8, 24.5, 22.7, 21.0, 19.4, 14.8, 13.4. HRMS (ESI+) [M+Na] + Calculated m / z for [C 34 H 52 [N2NaO9] + : 655.3565, found: 655.3566. 1-(5-((5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoyl)oxy)-1-methoxy-1-oxopentan-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3v)

[0076] Yield: 95 mg; Yield: 88%; Regioisomer ratio: 16:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.99 (d, J= 7.4 Hz, 1H), 6.66 – 6.61 (m, 2H), 6.58 – 6.35 (m, 1H), 4.71 – 4.60 (m, 1H), 4.25 – 4.13 (m, 6H), 3.96 – 3.88(m, 2H), 3.64 (s, 3H), 2.85 – 2.60 (m, 1H), 2.51 – 2.40 (m, 1H), 2.30 (s,3H), 2.17 (s, 3H), 1.99 – 1.89 (m, 1H), 1.78 – 1.70 (m, 5H), 1.30 – 1.25 (m,6H), 1.24 – 1.22 (m,6H). 13 C NMR(101 MHz, CDCl3) δ 177.9, 171.4, 157.5, 157.0,156.2, 136.5, 130.4, 123.6, 120.7, 112.0, 68.0, 63.0, 62.6, 62.4, 61.3, 53.0,52.0, 42.2, 37.2, 31.7, 29.8, 25.3, 25.2, 21.5, 15.8, 14.5.HRMS (ESI+)[M+Na] + Calculated m / z for [C 27 H 42 [N2NaO9] + : 561.2783, found: 561.2787. 1-(1-Methoxy-1,6-dioxo-6-(((1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl)oxy)hexyl-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3w)

[0077] Yield: 77 mg; Yield: 82%; Regioisomer ratio: 19:1; Diastereomer ratio: 1:1; Appearance: Pale yellow oily liquid; 1¹H NMR (400 MHz, CDCl₃, mixture of two diastereomers) δ 6.93 – 6.35 (m, 1H), 4.96 – 4.77 (m, 1H), 4.73 – 4.45 (m, 1H), 4.32 – 3.97 (m, 4H), 3.66 (s, 3H), 2.88 – 2.26 (m, 5H), 1.98 – 1.80 (m, 2H), 1.79 – 1.62 (m, 3H), 1.37 – 1.15 (m, 8H), 1.01 – 0.92 (m, 1H), 0.90 (s, 3H), 0.87 (s, 3H), 0.82 (s, 3H). 13 C NMR (101 MHz, DMSO-) d 6. A mixture of two diastereomers) δ 172.9, 171.2, 157.5, 157.3, 155.8, 79.3, 79.1, 62.2, 61.9, 61.3, 53.6, 52.1, 51.8, 48.8, 47.9, 44.7, 37.3, 36.70, 36.65, 30.6, 28.0, 27.2, 26.7, 20.0, 19.0, 14.8, 13.8. HRMS(ESI+)[M+Na] + Calculated m / z for [C 23 H 38 [N2NaO8] + : 493.2520, found: 493.2523. 1-(2-(3-(2-methoxy-2-oxoethyl)cyclohexyl-2-en-1-yl)propyl-2-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3x)

[0078] Yield: 17 mg, Yield: 23%; Appearance: Pale yellow oily liquid; 1H NMR (400 MHz, CDCl3) δ 6.37 – 6.05 (m, 1H), 5.61 – 5.50 (m, 1H), 4.29 – 4.06 (m, 4H), 3.69 (s, 3H), 3.03 – 2.91 (m, 2H), 2.56 – 2.39 (m, 1H), 2.16 – 2.01 (m, 2H), 1.95 – 1.83 (m, 2H), 1.81 – 1.43 (m, 6H), 1.30 – 1.23 (m, 6H), 1.22 – 1.15 (m, 2H). 13 C NMR (101 MHz, DMSO-) d 6) δ 172.0, 157.2, 155.3,131.4, 125.3, 65.1, 61.1, 51.8, 42.5, 29.6, 27.4, 26.9, 24.6, 24.3, 21.7,15.0, 14.9.HRMS (ESI+)[M+Na] + Calculated m / z for [C 18 H 30 [N2NaO6] + : 393.1996, found: 393.1993. 1-((4-(2-methoxy-2-oxoethyl)tetrahydrofuran-3-yl)methyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3y)

[0079] Yield: 53 mg; Yield: 80%; Diastereomer ratio: 1.1:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.17 – 6.39 (m, 1H), 4.28 – 4.08 (m, 4H), 4.06 – 3.81 (m, 2H), 3.68 (s, 1.4H), 3.66 (s, 1.6H), 3.63 – 3.57 (m, 1H),3.56 – 3.49 (m, 1H), 3.48 – 3.41 (m, 1H), 2.72 (dd, J = 8.4, 4.8 Hz, 1H), 2.58– 2.24 (m, 3H), 1.74 – 1.65 (m, 1H), 1.30 – 1.22 (m, 6H). 13C NMR (101 MHz, DMSO- d 6) δ 173.1, 172.9, 156.6, 156.0, 72.5, 72.1, 70.9, 70.4, 62.1, 61.2,51.9, 51.8, 37.1, 32.1, 29.8, 14.91, 14.85.HRMS (ESI+)[M+Na] + calculated m / z for [C 14 H 24 [N2NaO7] + : 355.1476, found: 355.1485. 1-(1-Benzamido-4-methoxy-4-oxobut-2-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3z)

[0080] Yield: 66 mg; Yield: 84%; Regioisomer ratio: 13:1; Appearance: Pale yellow oily liquid; 1 H NMR(400 MHz, CDCl3) δ 8.15 – 7.68 (m, 3H), 7.53 – 7.36 (m, 3H), 6.94 – 6.50 (m, 1H), 4.91 – 4.64 (m, 1H), 4.34 – 3.86 (m, 5H), 3.67 (s, 3H), 3.07 – 2.73 (m, 1H), 2.66 – 2.39 (m, 2H), 1.37 – 1.21 (m, 6H). 13 C NMR (101 MHz, DMSO- d 6) δ 171.1, 167.4, 167.2, 156.7, 155.9, 134.6, 131.9, 128.85, 128.76,127.5, 127.4, 62.2, 62.0, 61.5, 60.2, 54.2, 53.8, 51.8, 34.6, 14.8, 14.6.HRMS(ESI+)[M+Na] + Calculated m / z for [C 18 H 25 [N3NaO7] + : 418.1585, found: 418.1581. 1-(1-Methoxy-4,4-dimethyl-1-oxopentan-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3aa)

[0081] Yield: 20 mg; Yield: 31%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.73 – 5.96 (m, 1H), 4.71 – 4.02 (m, 5H), 3.66 (s, 3H), 2.80 – 2.43 (m, 2H), 1.30 – 1.23 (m, 6H), 1.08 – 0.89 (m, 9H). 13 C NMR (101 MHz, DMSO-) d 6) δ 171.5, 157.3, 155.4, 61.5, 61.3, 60.8, 59.7,51.2, 35.4, 31.2, 26.7, 26.6, 26.3, 14.5, 14.4.HRMS (ESI+)[M+Na] + calculated m / z for [C 14 H 26 [N2NaO6] + : 341.1683, found: 341.1689. 1-tert-butyl-2-methyl-3-(1,2-bis(ethoxycarbonyl)hydrazino)indoline-1,2-dicarboxylic acid ester (3ab)

[0082] Yield: 83 mg; Yield: 92%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.93 (d, J= 9.2 Hz, 1H), 7.36 – 7.19 (m, 2H), 7.09 – 6.91 (m, 1H), 6.58 – 6.15 (m, 1H), 6.10 – 5.56 (m, 1H), 5.22 – 4.98(m, 1H), 4.37 – 4.02 (m, 4H), 3.78 (s, 3H), 1.48 (s, 9H), 1.29 (t, J = 7.1Hz, 3H), 1.18 (t, J = 7.3 Hz, 3H). 13 C NMR (101 MHz, DMSO-) d 6) δ 170.9, 157.3,155.4, 150.6, 142.9, 129.8, 126.0, 123.0, 122.2, 113.7, 81.0, 64.9, 62.3,60.8, 60.5, 52.5, 27.7, 14.5, 14.3, 14.1.HRMS (ESI+)[M+Na] + Calculated m / z for [C 21 H 29 [N3NaO8] + : 474.1847, found: 474.1847. 1-(2-methoxycarbonyl-1-neovalerylindoline-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3ac)

[0083] Yield: 46 mg; Yield: 53%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 8.23 ​​(d, J = 8.6 Hz, 1H), 7.39 – 7.31 (m, 1H), 7.29 – 7.22 (m, 1H), 7.07 (t, J = 6.9 Hz, 1H), 6.36 – 6.03 (m, 1H), 5.98 –5.56 (m, 1H), 5.54 – 5.32 (m, 1H), 4.35 – 3.97 (m, 4H), 3.77 (s, 3H), 1.32 –1.26 (m, 12H), 1.17 (t, J = 7.2 Hz, 3H).13 C NMR (101 MHz, DMSO-) d 6) δ 175.9,171.1, 157.3, 154.6, 145.7, 129.6, 129.4, 126.2, 125.7, 123.9, 123.4, 117.9,117.7, 65.2, 62.2, 61.2, 61.1, 60.8, 53.0, 40.6, 27.71, 27.66, 14.3,13.9.HRMS (ESI+)[M+Na] + Calculated m / z for [C 21 H 29 [N3NaO7] + : 458.1898, found:458.1897. 1-tert-butyl-2-methyl-3-(1,2-bis(ethoxycarbonyl)hydrazino)-4-methylindoline-1,2-dicarboxylic acid ester (3ad)

[0084] Yield: 84.8 mg, Yield: 91%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.16 – 7.05 (m, 2H), 7.03 – 6.97 (m, 1H), 6.51 – 6.09 (m, 1H), 5.81 – 5.47 (m, 1H), 5.42 – 5.23 (m, 1H), 4.32 – 3.96(m, 4H), 3.72 (s, 3H), 2.33 (s, 3H), 1.49 (s, 9H), 1.32 – 1.12 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 171.1, 157.7, 152.2, 142.4, 132.5, 129.3, 127.4, 124.9,124.5, 123.7, 81.2, 66.6, 65.7, 62.5, 61.4, 52.9, 28.1, 20.3, 14.75,14.68.HRMS (ESI+)[M+Na] + Calculated m / z for [C 22 H 31[N3NaO8] + : 488.2003, found:488.2005. 1-tert-butyl-2-methyl-3-(1,2-bis(ethoxycarbonyl)hydrazino)-5-chloroindoline-1,2-dicarboxylic acid ester (3ae)

[0085] Yield: 70 mg; Yield: 72%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.6 Hz, 1H), 7.38 – 7.14 (m, 2H), 6.59 – 6.17 (m, 1H), 5.94 – 5.51 (m, 1H), 5.24 – 4.82 (m, 1H), 4.34 – 4.05(m, 4H), 3.79 (s, 3H), 1.48 (s, 9H), 1.29 (t, J = 7.1 Hz, 3H), 1.21 (t, J =7.3 Hz, 3H). 13 C NMR (101 MHz, DMSO-) d 6) δ 170.4, 155.6, 154.7, 150.5, 142.0,129.7, 126.4, 125.9, 114.7, 81.4, 64.9, 62.3, 60.9, 52.6, 27.7, 14.2,14.0.HRMS (ESI+)[M+Na] + Calculated m / z for [C 21 H 28 ClN3NaO8] + : 508.1457, found:508.1459. 1-tert-butyl-2-methyl-3-(1,2-bisethoxycarbonylhydrazyl)-6-methoxyindoline-1,2-dicarboxylic acid ester (3af)

[0086] Yield: 81.2 mg; Yield: 84%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1H NMR(400 MHz, CDCl3) 7.65 – 7.48 (m, 1H), 7.22 – 6.94 (m, 1H), 6.54(d, J = 10.8 Hz, 1H), 6.50 – 6.30 (m, 1H), 5.90 – 5.55 (m, 1H), 5.26 – 4.94(m, 1H), 4.35 – 4.01 (m, 4H), 3.90 – 3.73 (m, 6H), 1.67 – 1.44 (m, 9H), 1.32– 1.26 (m, 3H), 1.19 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, DMSO-) d 6) δ 171.6,160.9, 156.0, 154.9, 150.6, 144.6, 126.7, 118.0, 109.0, 108.4, 99.8, 81.2,65.5, 62.2, 61.3, 60.9, 55.3, 52.5, 27.7, 14.3.HRMS (ESI+)[M+Na] + calculated m / z for [C 22 H 21 [N3NaO9] + : 504.1953, found: 504.1957. 1-tert-butyl-2-methyl-3-(1,2-bisethoxycarbonylhydrazyl)-6-fluoroindoline-1,2-dicarboxylic acid ester (3ag)

[0087] Yield: 82.6 mg; Yield: 88%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 11.3 Hz, 1H), 7.20 (m, 1H), 6.76– 6.63 (m, 1H), 6.62 – 6.12 (m, 1H), 5.94 – 5.48 (m, 1H), 5.28 – 4.88 (m,1H), 4.34 – 4.03 (m, 4H), 3.79 (s, 3H), 1.64 – 1.45 (m, 9H), 1.28 (t,J = 7.1Hz, 3H), 1.19 (t, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, DMSO-) d 6) δ 170.3, 163.3 (d, J = 242.1 Hz), 155.4, 150.5, 144.4, 127.8, 109.1 (d, J = 23.6 Hz), 101.4 (d, J =29.1 Hz), 81.6, 66.0, 62.3, 60.9, 59.8, 52.6, 27.6, 14.2. 19 F NMR (376 MHz, CDCl3) δ -109.92, -110.29, -110.49.HRMS (ESI+)[M+Na] + Calculated m / z for [C 21 H 28 FN3NaO8] + : 492.1753, found: 492.1754. 1-tert-butyl-2-methyl-3-(1,2-bisethoxycarbonylhydrazyl)-7-(dimethylformamide)indoline-1,2-dicarboxylic acid ester (3ah)

[0088] Yield: 67 mg; Yield: 64%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.53 – 7.37 (m, 1H), 7.36 – 7.25 (m, 1H), 7.15 – 7.05 (m, 1H), 6.51 – 6.14 (m, 1H), 5.94 – 5.53 (m, 1H), 5.49 – 5.06(m, 1H), 4.39 – 3.93 (m, 4H), 3.78 (s, 3H), 3.04 (s, 3H), 2.86 (s, 3H), 1.47(s, 9H), 1.29 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, DMSO- d 6) δ 170.5, 167.6, 154.4, 150.8, 138.7, 130.3, 127.2, 124.4, 80.7,65.7, 62.3, 61.1, 52.5, 34.3, 27.6, 14.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 24 H 34 [N4NaO9] + : 545.2218, found: 545.2213. 1-tert-butyl-2-methyl-3-(1,2-bisethoxycarbonylhydrazyl)-3-methylindoline-1,2-dicarboxylic acid ester (3ai)

[0089] Yield: 55 mg; Yield: 59%; Regioisomer ratio: >20:1; Diastereomer ratio: 1.1:1; Appearance: Pale yellow oily liquid; 1 ¹H NMR (400 MHz, CDCl₃, mixture of two diastereomers) δ 8.02 – 7.77 (m, 1H), 7.67 – 7.41 (m, 1H), 7.37 – 7.11 (m, 1H), 7.06 – 6.92 (m, 1H), 6.72 – 6.05 (m, 1H), 5.46 – 4.97 (m, 1H), 4.33 – 3.89 (m, 4H), 3.79 (s, 1.8H), 3.76 (s, 1.2H), 1.66 – 1.38 (m, 12H), 1.34 – 1.07 (m, 6H). 13 C NMR (101 MHz, DMSO-) d6. A mixture of two diastereomers) δ 170.6, 170.4, 157.0, 156.5, 156.0, 155.8, 154.9, 154.7, 151.0, 150.9, 142.5, 142.3, 142.2, 133.5, 133.3, 129.9, 129.7, 129.5, 129.4, 125.6, 124.7, 124.2, 123.6, 123.0, 122.9, 122.8, 114.4, 113.9, 113.8, 113.7, 82.4, 81.4, 81.3, 71.4, 71.0, 68.8, 68.6, 68.2, 67.9, 67.7, 62.10,62.07, 62.0, 61.6, 61.3, 60.9, 52.4, 52.3, 28.4, 28.2, 28.1, 23.4, 23.0,22.8, 22.6, 15.0, 14.9, 14.5, 14.4.HRMS (ESI+)[M+Na] + Calculated m / z for [C 22 H 31 [N3NaO8] + : 488.2003, found: 488.2005. 1-(2-methoxycarbonyl-2,3-dihydrobenzofuran-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3aj)

[0090] Yield: 56 mg; Yield: 81%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.35 – 7.22 (m, 2H), 7.05 – 6.87 (m, 2H), 6.52 – 6.20 (m, 1H), 6.20 – 5.99 (m, 1H), 5.48 – 5.06 (m, 1H), 4.38 – 4.02(m, 4H), 3.81 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H). 13 CNMR (101 MHz, DMSO- d6) δ 169.9, 159.7, 157.2, 155.8, 130.5, 126.8, 126.3,122.4, 122.1, 121.5, 120.9, 110.0, 109.9, 82.1, 62.2, 61.2, 60.8, 52.6, 14.3,14.1.HRMS (ESI+)[M+Na] + Calculated m / z for [C 16 H 20 [N2NaO7] + : 375.1163, found:375.1165. 1-(5-(9H-carbazole-9-yl)-2-methoxycarbonyl-2,3-dihydrobenzofuran-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3ak)

[0091] Yield: 79 mg; Yield: 76%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 7.8 Hz, 2H), 7.51 – 7.36 (m, 4H), 7.36 – 7.23 (m, 4H), 7.14 (d, J = 8.5 Hz, 1H), 6.66 – 6.32 (m, 1H), 6.31 –6.08 (m, 1H), 5.63 – 5.30 (m, 1H), 4.35 – 4.07 (m, 4H), 3.87 (s, 3H), 1.29 –1.20 (m, 6H). 13 C NMR(101 MHz, CDCl3) δ 170.0, 159.4, 155.2, 141.4, 131.6,130.3, 126.0, 124.1, 123.3, 120.4, 120.0, 111.8, 109.8, 83.3, 63.5, 62.7,53.1, 14.5.HRMS (ESI+)[M+Na] + Calculated m / z for [C 28 H 27 [N3NaO7] + : 540.1741, found: 540.1736. 1-(2-Methoxycarbonyl-2,3-dihydrobenzo[b]thiophene-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3al)

[0092] Yield: 36 mg; Yield: 48%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 HNMR(400 MHz, CDCl3) δ 7.33 – 7.21 (m, 2H), 7.19 – 7.07 (m, 2H), 6.53 – 6.02 (m, 2H), 4.92 – 4.56 (m, 1H), 4.22 (m, 4H), 3.79 (s, 3H), 1.27 (m, 7.1Hz, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 171.0, 157.3, 155.9, 155.2, 134.9, 129.5,126.2, 125.2, 124.6, 121.9, 121.7, 121.4, 66.4, 62.2, 61.2, 60.8, 52.8, 50.3,49.9, 14.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 16 H 20 [N2NaO6S] + : 391.0934, found: 391.0935. 1-(3-Methoxy-3-oxo-1-phenylpropyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3am)

[0093] Yield: 60.8 mg; Yield: 90%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1H NMR (400 MHz, CDCl3) δ 7.38 – 7.28 (m, 5H), 6.65 – 6.05 (m, 1H), 5.99 – 5.71 (m, 1H), 4.33 – 4.05 (m, 4H), 3.65 (s, 3H), 3.21 – 3.10 (m, 1H), 3.00 – 2.84 (m, 1H), 1.32 – 1.21 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 170.5,157.2, 155.0, 139.2, 128.4, 128.2, 127.9, 127.6, 127.4, 61.7, 60.9, 60.2,57.7, 56.5, 51.4, 36.3, 35.4, 14.44, 14.37, 13.7.HRMS (ESI+)[M+H] + calculated m / z for [C 16 H 23 N2O6] + : 339.1551, found: 339.1553. 1-(1-tert-butoxy-4-methoxy-2-methyl-1,4-dioxobut-2-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3an)

[0094] Yield: 56.1 mg; Yield: 75%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, DMSO-) d 6) δ 9.60 – 8.76 (m, 1H), 4.11 – 4.00 (m, 4H), 3.59 – 3.53 (m, 3H), 3.04 – 2.61 (m, 2H), 1.54 – 1.47 (m, 3H), 1.39 – 1.34(m, 9H), 1.21 – 1.11 (m, 6H). 13 C NMR (101 MHz, DMSO-) d6) δ 170.1, 169.7, 156.4,156.1, 154.7, 154.4, 80.8, 80.5, 65.3, 61.7, 60.9, 60.8, 51.4, 51.1, 27.4,27.3, 14.5, 14.4.HRMS (ESI+)[M+Na] + Calculated m / z for [C 16 H 28 [N2NaO8] + : 399.1738, found: 399.1733. 1-(1-tert-butylamino-4-methoxy-1,4-dioxobut-2-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3ao)

[0095] Yield: 55.7 mg; Yield: 77%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 8.35 – 7.65 (m, 1H), 7.23 – 6.36 (m, 1H), 5.21 – 4.43 (m, 1H), 4.31 – 4.12 (m, 4H), 3.69 (s, 3H), 3.24 – 3.09 (m, 1H), 3.05 – 2.54 (m, 1H), 1.37 – 1.24 (m, 15H). 13 C NMR (101 MHz, DMSO-) d 6) δ 170.8,167.7, 157.9, 155.2, 154.3, 62.4, 61.6, 54.9, 51.5, 50.3, 33.4, 28.2, 14.4,14.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 15 H 27 [N3NaO7] + : 384.1741, found:384.1746. 1-(1-Cyano-3-methoxy-3-oxopropyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3ap)

[0096] Yield: 30.3 mg; Yield: 53%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.80 – 6.62 (m, 1H), 5.60 – 5.40 (m, 1H), 4.34 – 4.16 (m, 4H), 3.75 (s, 3H), 3.14 – 3.01 (m, 1H), 3.00 – 2.90 (m, 1H),1.36 – 1.27 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 168.7, 154.6, 116.9, 62.8,61.4, 52.0, 46.8, 34.7, 14.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 11 H 17 [N3NaO6] + : 310.1010, found: 310.1012. 1-(1-Methoxy-1,4-dioxohexyl-3-yl)hydrazine-1,2-dicarboxylic acid diethyl ester (3aq)

[0097] Yield: 35.4 mg; Yield: 56%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, DMSO-) d 6) δ 9.57 – 8.97 (m, 1H), 4.98 – 4.82 (m, 1H), 4.20 – 3.98 (m, 4H), 3.57 (s, 3H), 2.95 – 2.64 (m, 2H), 2.64 – 2.38 (m, 2H), 1.24 – 1.12 (m, 6H), 0.96 – 0.86 (m, 3H). 13 C NMR (101 MHz, DMSO-) d 6) δ 205.9,170.9, 156.4, 155.4, 154.5, 62.5, 62.3, 61.1, 51.6, 32.1, 31.7, 14.41, 14.36,7.5.HRMS (ESI+)[M+Na] +Calculated m / z for [C 13 H 22 [N2NaO7] + : 341.1319, found:341.1312. 1-(1-(dimethylphenylsilyl)-3-methoxy-3-oxopropyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3ar)

[0098] Yield: 42 mg; Yield: 53%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR(400 MHz, CDCl3) δ 7.58 – 7.48 (m, 2H), 7.41 – 7.32 (m, 3H), 6.81 – 6.33 (m, 1H), 4.23 – 4.11 (m, 4H), 4.11 – 3.89 (m, 1H), 3.60 (s, 3H),2.84 – 2.68 (m, 1H), 2.42 (dd, J = 15.7, 4.1 Hz, 1H), 1.29 – 1.23 (m, 6H), 0.53 – 0.34 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 171.6, 155.5, 137.2, 133.9,129.1, 127.7, 61.5, 60.7, 51.2, 47.7, 47.3, 32.9, 14.4, -3.5, -3.9, -4.9, -5.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 18 H 26 [N2SiNaO6] + : 419.1609, found:419.1610. 1-(1-(9H-carbazole-9-yl)-3-methoxy-3-oxopropyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3as)

[0099] Yield: 60.7 mg; Yield: 71%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1H NMR (400 MHz, DMSO-) d 6) δ 9.74 (s, 0.7H), 9.36 (s, 0.2H), 9.28 (s,0.1H), 8.21 – 8.04 (m, 2H), 7.86 – 7.61 (m, 2H), 7.56 – 7.36 (m, 2H), 7.34 –7.13 (m, 3H), 4.21 – 4.04 (m, 2H), 3.76 – 3.53 (m, 2H), 3.51 – 3.43 (m, 2H), 3.39 (s, 3H), 1.34 – 1.00 (m, 4.6H), 0.82 (t, J = 7.1 Hz, 0.9H), -0.03 (t, J =7.1 Hz, 0.5H). 13 C NMR (101 MHz, DMSO-) d 6) δ 169.6, 169.2, 155.2, 154.7, 139.0,125.9, 125.8, 125.6, 123.0, 120.1, 119.6, 119.4, 111.5, 63.8, 62.3, 61.5,60.6, 60.1, 51.80, 51.76, 51.7, 35.9, 35.2, 14.5, 14.39, 14.37, 14.3, 14.2,12.5.HRMS (ESI+)[M+H] + Calculated m / z for [C 22 H 25 N3O6] + : 450.1636, found:450.1636. (2R,3S)-2-(1,2-bisethoxycarbonylhydrazyl)pyrrolidine-1,3-dicarboxylic acid-1-tert-butyl ester-3-methyl ester (3at)

[0100] Yield: 44 mg; Yield: 55%; Regioisomer ratio: >20:1; Diastereomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1H NMR(400 MHz, CDCl3) δ 6.69 – 5.89 (m, 2H), 4.29 – 4.11 (m, 4H), 3.74 (s, 3H), 3.65 – 3.21 (m, 3H), 2.30 – 1.98 (m, 2H), 1.45 (s, 9H), 1.32 –1.23 (m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 173.1, 157.6, 154.5, 153.3, 79.8,79.6, 71.8, 62.3, 61.9, 61.5, 61.1, 52.6, 45.9, 28.5, 26.8, 14.9.HRMS (ESI+)[M+Na] + Calculated m / z for [C 17 H 29 [N3NaO8] + : 426.1847, found: 426.1847. 1-(3-methoxy-3-oxo-1-(2-oxozyrocyclohep-1-yl)propyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3au)

[0101] Yield: 53 mg; Yield: 71%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 7.86 – 7.43 (m, 1H), 6.00 – 5.55 (m, 1H), 4.30 – 4.09 (m, 4H), 3.70 (s, 3H), 3.63 – 3.43 (m, 2H), 3.38 – 3.14 (m, 1H), 2.93 – 2.73 (m, 1H), 2.58 – 2.35 (m, 2H), 1.79 – 1.52 (m, 6H), 1.30 – 1.23(m, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 174.7, 169.6, 156.6, 154.3, 64.3, 61.8,61.1, 60.8, 51.6, 36.9, 35.2, 29.2, 28.5, 22.9, 14.4, 14.3.HRMS (ESI+)[M+Na]+ Calculated m / z for [C 16 H 27 [N3NaO7] + : 396.1741, found: 396.1736. 1-(1-Ethylthio-3-methoxy-3-oxopropyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3av)

[0102] Yield: 46.4 mg; Yield: 72%; Regioisomer ratio: >20:1; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, DMSO-) d 6) δ 9.53 – 8.80 (m, 1H), 5.97 – 5.55 (m, 1H), 4.23 – 3.90 (m, 4H), 3.60 (s, 3H), 2.85 – 2.42 (m, 4H), 1.28 – 1.11 (m, 9H). 13 C NMR (101 MHz, DMSO-) d 6) δ 169.4, 156.8, 156.3, 155.0, 62.1, 61.0, 58.3,51.7, 37.6, 37.3, 23.9, 14.5, 14.4, 14.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 12 H 22 [N2NaO6S] + : 345.1091, found: 345.1092. 1-(3-Methoxy-3-oxopropyl)hydrazine-1,2-dicarboxylic acid diethyl ester (3aw)

[0103] Yield: 62.9 mg, Yield rate: 60%; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.80 – 6.73 (m, 1H), 4.20 (q, J = 7.1 Hz, 4H), 3.82 (t, J = 6.8 Hz, 2H), 3.69 (s, 3H), 2.66 (t,J = 6.9 Hz, 2H), 1.28 (t, J =7.1 Hz, 6H). 13 C NMR (101 MHz, DMSO-) d 6) δ 171.7, 156.7, 155.8, 155.5, 155.1,61.7, 60.9, 60.6, 51.4, 46.0, 45.4, 32.2, 31.9, 14.6, 14.5, 14.4.HRMS (ESI+)[M+H] + Calculated m / z for [C 10 H 19 N2O6] + : 263.1238, found: 263.1241. 1-(3-methoxy-3-oxopropyl)hydrazine-1,2-dicarboxylic acid di-tert-butyl ester (3ax)

[0104] Yield: 68.8 mg, Yield rate: 54%; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.52 – 6.04 (m, 1H), 3.77 (t, J = 6.8 Hz, 2H),3.69 (s, 3H), 2.64 (t, J = 6.8 Hz, 2H), 1.48 (s, 18H). 13 C NMR (101 MHz, DMSO-) d 6)δ 171.5, 155.0, 79.4, 51.3, 44.9, 31.9, 28.0, 27.8.HRMS (ESI+)[M+Na] + Calculated m / z for [C 14 H 26 [N2NaO6] + : 341.1683, found: 341.1681. 3-(1,2-bis(tert-butyloxycarbonyl)hydrazino)propionic acid (3ax')

[0105] Yield: 71.1 mg, Yield: 58%; Appearance: Pale yellow oily liquid; 1 H NMR (400 MHz, CDCl3) δ 6.80 – 6.40 (m, 1H), 3.78 (t, J = 6.7 Hz, 2H), 2.72 – 2.54 (m, 2H), 1.53 – 1.39 (m, 18H). 13 C NMR (101 MHz, DMSO-) d 6) δ 173.1,155.5, 155.3, 80.6, 80.1, 79.9, 47.0, 45.4, 33.1, 32.6, 28.5, 28.3.HRMS (ESI+)[M+Na] + Calculated m / z for [C 13 H 24 [N2NaO6] + : 327.1527, found: 327.1524. The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for synthesizing based on the nitrogen carboxylation reaction of olefins and heteroaromatics N -amino- β A method for using amino acid compounds, characterized in that... Includes the following steps: An olefin or heteroaromatic hydrocarbon, an acyl hydrazine, a photocatalyst, and an alkaline substance are mixed, and then a solvent and additives are added under a CO2 atmosphere to obtain a reaction solution. The resulting reaction solution is stirred under light irradiation at 0–100 °C for 0.1–100 hours to obtain the desired product. N -amino- β -Amino acid compounds; The general structural formula of the olefin is shown in formula (I): Among them, R 1 R 2 R 3 and R 4 All are hydrogen, alkyl, aryl, heteroaryl, ester, amide, cyano, carbonyl, or heteroatoms protected by protecting groups; The general structural formula of heteroaromatic hydrocarbons is shown in formula (II): Where X is a heteroatom or a heteroatom protected by a protecting group; R 5 R 6 R 7 R 8 and R 9 All are hydrogen, alkyl, alkoxy, halogen, amide, or aryl groups; The general structural formula of hydrazides is shown in formula (III): Among them, R 10 It is an alkyl or alkoxy group.

2. The method according to claim 1, characterized in that, The structural formulas of olefins are shown below: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 3. The method according to claim 1, characterized in that, The structural formulas of heteroaromatic hydrocarbons are shown below: 、 、 、 、 、 、 、 、 、 、 。 4. The method according to claim 1, characterized in that, The structural formula of acylhydrazide is shown below: 、 、 。 5. The method according to any one of claims 1-4, characterized in that, The molar ratio of olefins or heteroaromatics, acyl hydrazides, photocatalysts, alkaline substances and additives is 1 : (0.1~10) : (0.001~1) : (0.1~10) : (0.1~10).

6. The method according to any one of claims 1-4, characterized in that, The photocatalyst is a DA-type photocatalyst or an organometallic photocatalyst.

7. The method according to claim 6, characterized in that, Photocatalyst is fac -Ir(ppy)3、 fac -Ir(dF(ppy)3) and fac At least one of -Ir(dtbppy)3.

8. The method according to any one of claims 1-4, characterized in that, The alkaline substance is at least one of tert-butoxide, carbonate, fluoride, carboxylate, phosphate and organic base; the additive is at least one of organic amine, formate and silane; the solvent is DMSO, NMP, DMF or DMAc.

9. The method according to claim 8, characterized in that, tert-Butanol salt is KO t Bu, NaO t Bu、LiO t Bu or Ca(O t Bu)2; carbonates are Cs2CO3, K2CO3, Na2CO3, or Li2CO3; fluorides are CsF, KF, NaF, or LiF; phosphates are K3PO4, Na3PO4, or Li3PO4; carboxylates are CsOAc, KOAc, NaOAc, CsOPiv, NaOPiv, or KOPiv; organic bases are DBU, TBD, DABCO, TMG, DBN, TMEDA, Cy2NEt, Cy2NMe, PMP, NBu3, NMe3, or NEt3; organic amines are Et3N i Pr2NEt, Me3N, Bu3N, Cy2NEt, Cy2NMe, TEOA, TMEDA, PMP, DBU, TBD, DABCO, TMG, or DBN; formates are HCOOCs, HCOOK, HCOONa, HCOOLi, (HCOO)2Ca, (HCOO)2Zn, HCOONH4, or HCOONBu4; silanes are PMHS, Et3SiH, MeEt2SiH, Me2EtSiH, i Pr3SiH, n Pr3SiH, n Hex3SiH, PhSiH3, Ph2SiH2, Ph3SiH, PhMe2SiH, Ph2MeSiH, BnMe2SiH, (MeO)3SiH, Me(MeO)2SiH, (EtO)3SiH, Me(EtO)2SiH, ( i PrO)3SiH, (Me3Si)3SiH, Me(Me3Si)2SiH or 1,4-di(dimethylsilyl)benzene.

10. The method according to claim 1, characterized in that, The reaction pressure is 0.1 to 30 times atmospheric pressure, the light source wavelength is 300 to 700 nm, and the light source power is 0.1 to 100 W.

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