A method for synthesizing distal amino alcohol compounds

Abstract

The present invention relates to a method for synthesizing a distal amino alcohol compound, comprising the steps of electrolyzing a cyclic amine compound represented by formula (I) to obtain a distal amino alcohol compound represented by formula (II). The present invention adopts an electrochemical method to directly electrolyze cyclic amines and (high) proline peptide compounds to obtain distal amino alcohol compounds, without the need for pre-preparation of reaction precursors, avoiding the use of noble metal catalysts and stoichiometric oxidants, avoiding the generation of chemical waste, and contributing to the realization of atom economy. The method is simple to operate, has high product purity, is easy to purify, has high efficiency and yield, low production cost, mild reaction conditions, and does not require inert gas protection. By using water as a green solvent and a source of hydroxyl groups, the reaction system is greener, more environmentally friendly, safer, more economical, energy-saving and environmentally friendly, and is more conducive to the realization of industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing a distal amino alcohol compound. Background Art

[0002] Amino alcohols possess amine (NHx) and hydroxyl (OH) functional groups capable of binding to Lewis acids and transition metals, making them highly valuable in synthetic chemistry, materials science, and polymer chemistry. They can be used as surfactants, petroleum additives, organic synthesis raw materials, and pharmaceutical intermediates. Many widely used clinical drugs contain amino alcohol structural units. Furthermore, they can be used as corrosion inhibitors, in boiler water treatment, and as coolants in automotive engines. While most current research focuses on 1,2-amino alcohols, relatively little research has been conducted on distal amino alcohols (such as 1,3-, 1,4-, 1,5-, 1,6-, and 1,7-amino alcohols). The construction of distal amino alcohols has been hampered by limitations in starting materials and methods. Traditional methods include azoaldehyde condensation (Chem. Commun. 2014, 50, 942.), metal-mediated olefin functionalization (J.Am.Chem.Soc. 2021, 143, 12467. Angew.Chem.Int.Ed. 2023, 62, e202305669.), intermolecular C-H amination of alkanes (J.Am.Chem.Soc. 2018, 140, 1612. Org.Lett. 2021, 23, 8968.), and nucleophilic addition of semicyclic N, O-acetals (J.Am.Chem.Soc. 2001, 123, 12510. J.Org.Chem. 2019, 84, 11261.), etc. However, these methods typically require pre-prepared precursors or require heating, noble metal photocatalysis, or sensitive Grignard reagents. These methods are complex, demanding, and environmentally hazardous. Furthermore, they primarily produce 1,3- and 1,4-amino alcohols, with limited application to more distal amino alcohols such as 1,5-amino alcohols. Therefore, there is an urgent need for a general method for the direct synthesis of distal amino alcohols. Summary of the Invention

[0003] Based on this, the purpose of the present invention is to provide a method for synthesizing a distal amino alcohol compound.

[0004] The technical solutions for achieving the above-mentioned purpose include the following.

[0005] A method for synthesizing a distal amino alcohol compound comprises the following steps:

[0006] Electrolyzing the cyclic amine compound represented by formula (I) to obtain the distal amino alcohol compound represented by formula (II),

[0007]

[0008] Among them, R 1 Selected from: aryl, arylformyl, alkylacyl;

[0009] Each R 2 are independently selected from: hydrogen, alkoxy, halogen, aryl, alkyl, alkoxycarbonyl, or two adjacent R 2 Together with the carbon atom to which it is attached, it forms a cycloalkyl group;

[0010] R is selected from: hydrogen, alkoxy, halogen, aryl, alkyl,

[0011] Each R 3 are independently selected from: amino acids or their esters after removing an amino hydrogen, dipeptides or their esters after removing an amino hydrogen, tripeptides or their esters after removing an amino hydrogen, R 4 Substituted or unsubstituted alkylamino, R 4 Substituted or unsubstituted cycloalkylamino, R 4 Substituted or unsubstituted alkoxy, R 4 a substituted or unsubstituted cycloalkoxy group;

[0012] Each R 4 Each of the following groups is independently selected from the group consisting of amino, protected amino, cyano, alkenyl, and alkoxycarbonyl;

[0013] R 5 Selected from: hydrogen, methyl, ethyl;

[0014] R 6 Selected from: hydrogen, methoxy, ethoxy;

[0015] n is selected from: 0, 1, 2, 3, 4;

[0016] m is selected from: 0, 1, 2, 3, 4, 5, 6.

[0017] In some embodiments, the cyclic amine compound has a structure shown in the following formula (III):

[0018]

[0019] The distal amino alcohol compound has a structure shown in the following formula (IV):

[0020]

[0021] n is selected from: 0, 1, 2, 3, 4;

[0022] m is selected from: 0, 1, 2, 3.

[0023] In some embodiments, the cyclic amine compound has a structure shown in the following formula (V):

[0024]

[0025] The distal amino alcohol compound has a structure shown in the following formula (VI):

[0026]

[0027] n is selected from: 1, 2, 3.

[0028] In some embodiments, R 1 Selected from: C6-C 10 Aryl, C6-C 10 Arylformyl, C1-C 12 Alkyl acyl.

[0029] In some embodiments, R 1 Selected from: phenyl, benzoyl, C1-C6 alkyl acyl.

[0030] In some embodiments, R 1 Selected from: phenyl, benzoyl, pivaloyl.

[0031] In some embodiments, each R 2 are independently selected from: hydrogen, C1-C 12 Alkoxy, halogen, C6-C 10 Aryl, C1-C 12 Alkyl, C1-C 12 Alkoxycarbonyl, or two adjacent R2 together with the carbon atom to which they are attached form a C3-C 12 Cycloalkyl.

[0032] In some embodiments, each R 2 are independently selected from: hydrogen, C1-C6 alkoxy, halogen, C6-C 10 Aryl, C1-C6 alkyl, C1-C6 alkoxycarbonyl, or two adjacent R2 together with the carbon atom to which they are attached form a C3-C8 cycloalkyl.

[0033] In some embodiments, each R 2 are independently selected from: hydrogen, C1-C3 alkoxy, halogen, phenyl, C1-C3 alkyl, C1-C3 alkoxycarbonyl, or two adjacent R 2 Together with the carbon atom to which it is attached, it forms a C3-C6 cycloalkyl group.

[0034] In some embodiments, each R 2are independently selected from: hydrogen, methoxy, fluorine, phenyl, chlorine, methyl, methoxycarbonyl, or two adjacent R 2 Together with the carbon atom to which it is connected, it forms a cyclopropyl or cyclopentyl group.

[0035] In some embodiments, R is selected from the group consisting of: hydrogen, C1-C 12 Alkoxy, halogen, C6-C 10 Aryl, C1-C 12 alkyl,

[0036] Each R 3 are independently selected from: amino acids or their esters after removing an amino hydrogen, dipeptides or their esters after removing an amino hydrogen, tripeptides or their esters after removing an amino hydrogen, R 4 Substituted or unsubstituted C1-C 12 Alkylamino, R 4 Substituted or unsubstituted C3-C 12 Cycloalkylamino, R 4 Substituted or unsubstituted C1-C 12 Alkoxy, R 4 Substituted or unsubstituted C3-C 12 cycloalkoxy;

[0037] Each R 4 Each independently selected from: amino, protected amino, cyano, alkenyl, C1-C 12 Alkoxycarbonyl.

[0038] In some embodiments, R is selected from the group consisting of hydrogen, C1-C6 alkoxy, halogen, C6-C 10 Aryl, C1-C6 alkyl,

[0039] Each R 3 are independently selected from: amino acids or their esters after removing an amino hydrogen, dipeptides or their esters after removing an amino hydrogen, tripeptides or their esters after removing an amino hydrogen, R 4 Substituted or unsubstituted C1-C6 alkylamino, R 4 Substituted or unsubstituted C3-C 10 Cycloalkylamino, R 4 Substituted or unsubstituted C1-C6 alkoxy, R 4 Substituted or unsubstituted C3-C8 cycloalkoxy;

[0040] Each R 4 Each is independently selected from the group consisting of amino, protected amino, cyano, alkenyl, and C1-C6 alkoxycarbonyl.

[0041] In some embodiments, R is selected from hydrogen, methoxy, fluorine, phenyl, chlorine, methyl, methoxycarbonyl, or a group selected from the following structures:

[0042]

[0043] In some embodiments, the cyclic amine compound is selected from the following compounds:

[0044]

[0045]

[0046] The distal amino alcohol compound is selected from the following compounds:

[0047]

[0048]

[0049] In some embodiments, the electrolysis is performed in a single-chamber electrolysis cell containing an electrolyte.

[0050] In some embodiments, the solvent in the electrolyte is water, methanol, ethanol, acetone, or a mixed solvent of acetone and water.

[0051] In some embodiments, the volume ratio of acetone to water in the mixed solvent of acetone and water is 1:1-8.

[0052] In some embodiments, the volume ratio of acetone to water in the mixed solvent of acetone and water is 1:6-8.

[0053] In some embodiments, R 5 and R 6 The electrolyte is hydrogen, and the solvent is water or a mixed solvent of acetone and water.

[0054] In some embodiments, R 5 is methyl, R 6 is a methoxy group, and the solvent in the electrolyte is methanol.

[0055] In some embodiments, R 5 is ethyl, R 6 The solvent in the electrolyte is ethanol.

[0056] In some embodiments, the electrolyte in the electrolyte is one or more of tetrabutylammonium hydrogen sulfate, ammonium sulfate, and tetrabutylammonium perchlorate.

[0057] In some embodiments, a copper compound is added to the electrolyte.

[0058] In some embodiments, the copper compound is one or more of tetraacetonitrile copper tetrafluoroborate, tetraacetonitrile copper hexafluorophosphate, copper trifluoromethanesulfonate, cupric chloride, cuprous chloride, copper bromide, and cuprous iodide.

[0059] In some embodiments, the molar ratio of the cyclic amine compound to the electrolyte is 1:0.5-1.5.

[0060] In some embodiments, the molar ratio of the cyclic amine compound to the electrolyte is 1:0.8-1.2.

[0061] In some embodiments, the molar concentration of the electrolyte in the electrolyte solution is 0.02 mmol / mL-0.08 mmol / mL.

[0062] In some embodiments, the molar concentration of the electrolyte in the electrolyte solution is 0.04 mmol / mL-0.06 mmol / mL.

[0063] In some embodiments, the molar ratio of the cyclic amine compound to the copper compound is 1:0.1-0.8.

[0064] In some embodiments, the molar ratio of the cyclic amine compound to the copper compound is 1:0.2-0.5.

[0065] In some embodiments, the molar ratio of the cyclic amine compound to the copper compound is 1:0.2-0.3.

[0066] In some embodiments, the molar ratio of the cyclic amine compound to the copper compound is 1:0.4-0.5.

[0067] In some embodiments, the molar concentration of the copper compound in the electrolyte is 0.004 mmol / mL-0.04 mmol / mL.

[0068] In some embodiments, the molar concentration of the copper compound in the electrolyte is 0.01 mmol / mL-0.025 mmol / mL.

[0069] In some embodiments, the anode for electrolysis is a graphite sheet or carbon felt, and the cathode is a graphite sheet, carbon felt, platinum sheet or copper sheet.

[0070] In some embodiments, the electrolysis is performed using a constant current with a current intensity of 4 mA to 30 mA, and the amount of current applied is 4.5 F / mol to 34 F / mol based on the amount of the cyclic amine compound.

[0071] In some embodiments, the current intensity is 8 mA to 20 mA, and the amount of current applied is 8.9 F / mol to 22.5 F / mol based on the amount of the cyclic amine compound.

[0072] In some embodiments, the current intensity is 6 mA to 10 mA, and the amount of current applied is 6.7 F / mol to 11.3 F / mol based on the amount of the cyclic amine compound.

[0073] In some embodiments, the current intensity is 12 mA to 20 mA, and the amount of current applied is 13.3 F / mol to 22.5 F / mol based on the amount of the cyclic amine compound.

[0074] In some embodiments, the electrolysis temperature is 20°C-30°C.

[0075] The present invention provides an innovative method for synthesizing distal amino alcohols. This method can directly synthesize distal amino alcohol compounds through the electrochemical ring-opening reaction of cyclic amines. Compared with the existing technology, the electrochemical synthesis method of distal amino alcohol compounds of the present invention has the following advantages:

[0076] Continuous paired electrolysis is carried out under mild, biocompatible reaction conditions without the need for heating or inert gas protection, avoiding the use of precious metal catalysts and stoichiometric oxidants, greatly reducing the difficulty of purifying the reaction products. Electrons are used as oxidants during the reaction process, and the reaction system is clean and environmentally friendly, avoiding the generation of chemical waste and helping to achieve atom economy.

[0077] This method is simple to operate and does not require the preparation of reaction precursors. It can directly prepare various remote amino alcohols and peptide alcohols in one step through the electrochemical ring opening of cyclic amines with water or alcohols. The products are high in purity, easy to purify, with high efficiency and yield, and low production cost.

[0078] The method utilizes water or alcohol as a green solvent and a hydroxyl source or an alkoxy source, and the reaction system is greener, more environmentally friendly, safer, more economical, energy-saving and environmentally friendly, and is more conducive to industrial production. DETAILED DESCRIPTION

[0079] To facilitate understanding of the present invention, the present invention will be described more fully below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the present disclosure more thorough and comprehensive.

[0080] The experimental methods in the following examples where specific conditions are not specified are generally carried out under conventional conditions or conditions recommended by the manufacturers.

[0081] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art to which this invention pertains. The terms used in this specification are for the purpose of describing specific embodiments only and are not intended to limit the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0082] Furthermore, as used herein, the term "or" is inclusive and equivalent to the term "and / or," unless the context clearly dictates otherwise. The term "based on" is not exclusive and allows for being based on other factors not described, unless the context clearly dictates otherwise. Furthermore, throughout this specification, the meanings of "a," "an," and "the" include plural referents. The meaning of "in" includes "in" and "on."

[0083] In the compounds of the present invention, when any variable (such as R 2 If a substituent (e.g., ) occurs more than once in any component, its definition at each occurrence is independent of its definition at every other occurrence. Likewise, combinations of substituents and variables are permissible so long as such combinations result in a stable compound. A line drawn from a substituent into a ring system or carbon chain indicates that the indicated bond may be attached to any substitutable ring atom. If the ring system is polycyclic, this means that such bonds may be attached only to any suitable carbon atom in an adjacent ring. It will be understood that one of ordinary skill in the art can select substituents and substitution patterns in the compounds of the present invention to provide compounds that are chemically stable and readily synthesized from readily available starting materials using techniques in the art and the methods set forth below. If a substituent is itself substituted with more than one group, it will be understood that these groups may be on the same carbon atom or on different carbon atoms so long as the structure is stable.

[0084] As used herein, the term "alkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having a specified number of carbon atoms. For example, the definition of "C1-C6 alkyl" includes groups having 1, 2, 3, 4, 5, or 6 carbon atoms in a straight or branched arrangement. For example, "C1-C6 alkyl" specifically includes methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, pentyl, and hexyl.

[0085] The term "cycloalkyl" as used herein refers to a saturated or unsaturated non-aromatic monocyclic, condensed, bridged, or spirocyclic hydrocarbon group having a specific number of carbon atoms. For example, "cycloalkyl" includes cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0086] The term "alkoxy" used in the present invention refers to a group having an -O-alkyl structure, such as -OCH3, -OCH2CH3, -OCH2CH2CH3, -O-CH2CH(CH3)2, -OCH2CH2CH2CH3, -O-CH(CH3)2, etc.

[0087] The term "halogen" as used herein refers to chlorine, fluorine, bromine and iodine.

[0088] In the compounds of the present invention, Piv refers to pivaloyl, i.e., trimethylacetyl; and Bz refers to benzoyl.

[0089] The room temperature mentioned in the present invention refers to 23°C-25°C.

[0090] The present invention is further described in detail below with reference to specific embodiments.

[0091] The starting materials and reagents used in the following examples are all commercially available conventional raw materials and reagents, or the substrates required for electrolysis can be synthesized by known methods reported in the literature.

[0092] Example 1: Electrochemical synthesis of compound 1b

[0093]

[0094] In a 30 mL single-chamber electrolytic cell, raw material 1a (0.2 mmol), Cu(MeCN)4BF4 (0.04 mmol, i.e., 20% of raw material 1a) and electrolyte Bu4NHSO4 (0.2 mmol) were added to 4 mL of water. Electrolysis was carried out at a constant current of 8 mA using a graphite sheet electrode as the anode and a graphite sheet electrode as the cathode. After stirring at room temperature for 6 hours, the electrolysis was stopped, and the reaction solution was transferred, concentrated, and purified by column chromatography to obtain 1b as a colorless liquid in a yield of 82%.

[0095] The characterization data of compound 1b are as follows: 1 H NMR (400MHz, CDCl3) δ = 5.78 (s, 1H), 3.61 (t, J = 6.4Hz, 2H), 3.22 (dd, J = 13.0, 6.8Hz, 2H), 1.61-1.46 (m, 4H), 1.42-1.34 (m, 2H), 1.16 (s, 9H);

[0096] 13 C NMR (100MHz, CDCl3) δ = 178.8, 62.5, 39.5, 38.7, 32.2, 29.5, 27.7, 23.1;

[0097] HR-MS(ESI)m / z calcd for:C 10 H22 NO2[M+H] + 188.1645, found 188.1638.

[0098] Example 2: Electrochemical synthesis of compound 2b

[0099]

[0100] 2a (0.2 mmol) was used as the starting material, and according to the method and reaction conditions of Example 1, 2b was prepared as a colorless liquid in a yield of 59%.

[0101] The characterization data of compound 2b are as follows: 1 H NMR (400MHz, CDCl3)δ=7.78-7.72(m,2H),7.49-7.44(m,1H),7.43-7.36(m,2H),6.46(s,1H) ,3.63(t,J=6.3Hz,2H),3.44(dd,J=13.0,6.9Hz,2H),1.67-1.55(m,4H),1.49-1.39(m,4H);

[0102] 13 C NMR (100MHz, CDCl3) δ = 167.9, 134.8, 131.5, 128.6, 127.0, 62.6, 40.0, 32.2, 29.5, 23.2;

[0103] MS(ESI)m / z calcd for:C 12 H 18 NO2[M+H] + 208.1332, found 208.1334.

[0104] Example 3: Electrochemical synthesis of compound 3b

[0105]

[0106] 3b was prepared from 3a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 1 in a yield of 59%.

[0107] The characterization data of compound 3b are as follows: 1 H NMR (400MHz, CDCl3) δ = 6.38 (s, 1H), 3.80-3.66 (m, 2H), 3.55-3.45 (m, 1H), 3.39-3.23 (m, 5H), 1.85-1.72 (m, 3H), 1.72-1.62 (m, 1H), 1.15 (s, 9H);

[0108] 13 C NMR (100MHz, CDCl3) δ = 178.8, 79.3, 60.0, 56.7, 38.7, 37.0, 35.4, 32.2, 27.6;

[0109] HR-MS(ESI)m / z calcd for:C 11 H 24 NO3[M+H] + 218.1751,found 218.1751.

[0110] Example 4: Electrochemical synthesis of compound 4b

[0111]

[0112] Using 4a (0.2 mmol) as starting material, according to the method and reaction conditions of Example 1, 4b was prepared as a colorless liquid in a yield of 62%.

[0113] The characterization data of compound 4b are as follows: 1 H NMR (400MHz, CDCl3) δ = 6.15 (s, 1H), 3.83 (t, J = 6.1Hz, 2H), 3.45 (q, J = 6.3Hz, 2H), 2.20-2.07 (m, 4H), 1.16 (s, 9H);

[0114] 13 C NMR(100MHz, CDCl3)δ=179.1,124.9(t, 1 J C-F =240.7Hz Hz),56.7(t, 3 J C-F =6.1Hz),39.3(t, 2 J C-F =24.3Hz),38.7,36.2(t, 2 J C-F =24.2Hz),33.8(t, 3 J C-F =5.2Hz),27.5;

[0115] 19 F NMR (376MHz, CDCl3) δ = -95.39 (m).

[0116] HR-MS(ESI)m / z calcd for:C 10 H 20 F2NO2[M+H] +224.1457, found 224.1458.

[0117] Example 5: Electrochemical synthesis of compound 5b

[0118]

[0119] 5b was prepared from 5a (0.2 mmol) as a brown liquid according to the method and reaction conditions of Example 1. The yield was 49%.

[0120] The characterization data of compound 5b are as follows: 1 H NMR(400MHz, CDCl3)δ=7.34v7.28(m,2H),7.24-7.16(m,3H),5.51(s,1H),3.59-3.39(m,2H) ),3.27-3.05(m,2H),2.83-2.71(m,1H),1.98-1.90(m,2H),1.86-1.75(m,2H),1.08(s,9H);

[0121] 13 C NMR (100MHz, CDCl3) δ = 178.7, 144.5, 128.9, 127.7, 126.8, 60.7, 40.5, 39.5, 38.7, 38.4, 36.5, 27.6;

[0122] HR-MS(ESI)m / z calcd for:C 16 H 26 NO2[M+H] + 264.1958,found 264.1958.

[0123] Example 6: Electrochemical synthesis of compound 6b

[0124]

[0125] Using 6a (0.2 mmol) as starting material, according to the method and reaction conditions of Example 1, 6b was prepared as a colorless liquid in a yield of 39%.

[0126] The characterization data of compound 6b are as follows: 1 H NMR (400MHz, CDCl3) δ = 6.02 (s, 1H), 4.20-4.11 (m, 1H), 3.86-3.75 (m, 2H), 3.53-3.31 (m, 2H), 2.13-2.01 (m, 2H), 1.96-1.83 (m, 2H), 1.18 (s, 9H);

[0127] 13 C NMR (100MHz, CDCl3) δ = 179.2, 59.4, 58.3, 40.9, 38.8, 38.1, 37.3, 27.7;

[0128] HR-MS(ESI)m / z calcd for:C 10 H 21 ClNO2[M+H] + 222.1255, found 222.1257.

[0129] Example 7: Electrochemical synthesis of compound 7b

[0130]

[0131] 7b was prepared from 7a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 1 in a yield of 74%.

[0132] The characterization data of compound 7b are as follows: 1 H NMR (400MHz, CDCl3) δ = 5.41 (d, J = 7.2Hz, 1H), 4.02-3.89 (m, 1H), 3.66-3.54 (m, 2H),1.63-1.48(m,2H),1.47-1.30(m,4H),1.16(s,9H),1.10(d,J=6.6Hz,3H);

[0133] 13 C NMR (100MHz, CDCl3) δ = 178.1, 62.6, 44.9, 38.7, 36.9, 32.4, 27.7, 22.3, 21.1;

[0134] HR-MS(ESI)m / z calcd for:C 11 H 24 NO2[M+H] + 202.1802,found 202.1801.

[0135] Example 8: Electrochemical synthesis of compound 8b

[0136]

[0137] 8b was prepared from 8a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 1 in a yield of 67%.

[0138] The characterization data of compound 8b are as follows: 1H NMR (400MHz, CDCl3) δ = 5.78 (s, 1H), 3.66-3.41 (m, 2H), 3.29-3.01 (m, 2H), 1.72-1.26 (m, 5H), 1.18 (s, 9H), 0.90 (d, J = 1.8Hz, 3H);

[0139] 13 C NMR (100MHz, CDCl3) δ=178.9,178.8,68.0,62.9,45.1,39.7,38.9,38.8,35.3,33.3,30.3,30.2,29.8,27.74,27.71,27.1,17.8,16.7;

[0140] HR-MS(ESI)m / z calcd for:C 11 H 24 NO2[M+H] + 202.1802, found 202.1803.

[0141] Example 9: Electrochemical synthesis of compound 9b

[0142]

[0143] Using 9a (0.2 mmol) as starting material, according to the method and reaction conditions of Example 1, 9b was prepared as a colorless liquid in a yield of 51%.

[0144] The characterization data of compound 9b are as follows: 1 H NMR (400MHz, CDCl3) δ = 6.20 (d, J = 7.8Hz, 1H), 4.64-4.55 (m, 1H), 3.74 (s, 3H), 3.67- 3.58(m,2H),1.91-1.82(m,1H),1.73-1.51(m,3H),1.47-1.32(m,2H),1.21(s,9H);

[0145] 13 C NMR (100MHz, CDCl3) δ = 178.6, 173.5, 62.5, 52.5, 51.9, 38.9, 32.5, 32.1, 27.6, 21.6;

[0146] HR-MS(ESI)m / z calcd for:C 12 H 24 NO4[M+H] + 246.1700,found 246.1700.

[0147] Example 10: Electrochemical synthesis of compound 10b

[0148]

[0149] 10b was prepared from 10a as a colorless liquid according to the method and reaction conditions of Example 1 in a yield of 68%.

[0150] The characterization data of compound 10b are as follows: 1 H NMR (400MHz, CDCl3) δ = 6.00 (s, 1H), 3.65 (t, J = 5.8Hz, 2H), 3.25 (q, J = 6.5Hz, 2H), 1.62-1.53 ​​(m, 4H), 1.17 (s, 9H);

[0151] 13 C NMR (100MHz, CDCl3) δ = 179.0, 62.3, 39.4, 38.8, 29.7, 27.7, 26.3;

[0152] HR-MS(ESI)m / z calcd for:C9H 20 NO2[M+H] + 174.1489, found 174.1491.

[0153] Example 11: Electrochemical synthesis of compound 11b

[0154]

[0155] 11b was prepared from 11a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 1 in a yield of 50%.

[0156] The characterization data of compound 11b are as follows: 1 HNMR (400MHz, CDCl3) δ = 6.48 (d, J = 7.1Hz, 1H), 4.62-4.54 (m, 1H), 3.73 (s, 3H), 3.65 (t ,J=5.7Hz,2H),1.98-1.87(m,1H),1.84-1.72(m,1H),1.62-1.53(m,2H),1.19(s,9H);

[0157] 13 C NMR (100MHz, CDCl3) δ = 178.8, 173.4, 62.0, 52.5, 51.9, 38.8, 29.4, 28.2, 27.5;

[0158] HR-MS(ESI)m / z calcd for:C11 H 22 NO4[M+H] + 232.1543, found 232.1545.

[0159] Example 12: Electrochemical synthesis of compound 12b

[0160]

[0161] Compound 12b was prepared from compound 12a as a brown solid according to the method and reaction conditions of Example 1 in a yield of 78%.

[0162] The characterization data of compound 12b are as follows: 1 H NMR(400MHz, CDCl3)δ=7.79-7.71(m,2H),7.49-7.42(m,1H),7.42-7.34(m,2H) ,6.84(s,1H),3.67(t,J=5.9Hz,2H),3.45(q,J=6.5Hz,2H),1.76-1.56(m,4H);

[0163] 13 C NMR (100MHz, CDCl3) δ = 168.0, 134.7, 131.5, 128.6, 127.0, 62.3, 39.9, 29.9, 26.3;

[0164] HR-MS(ESI)m / z calcd for:C 11 H 16 NO2[M+H] + 194.1176, found 194.1179.

[0165] Example 13: Electrochemical synthesis of compound 13b

[0166]

[0167] 13b was prepared from 13a (0.2 mmol) as a white solid according to the method and reaction conditions of Example 1 in a yield of 56%.

[0168] The characterization data of compound 13b are as follows: 1H NMR (400MHz, CDCl3) δ = 6.73 (s, 1H), 4.07 (dd, J = 11.8, 4.8Hz, 1H), 3.87-3.78 (m, 1H), 3.56 (s, 1H), 3.23 (t, J =11.3Hz,1H),2.83-2.72(m,1H),1.17(s,9H),1.07-0.97(m,1H),0.76-0.66(m,1H),0.06(q,J=5.4Hz,1H);

[0169] 13 C NMR (100MHz, CDCl3) δ = 179.1, 62.4, 38.9, 38.8, 27.6, 18.0, 15.8, 7.4;

[0170] HR-MS(ESI)m / z calcd for:C 10 H 19 NO2Na + [M+Na] + 208.1308, found 208.1306.

[0171] Example 14: Electrochemical synthesis of compound 14b

[0172]

[0173] Compound 14b was prepared from compound 14a as a colorless liquid according to the method and reaction conditions of Example 1 in a yield of 38%.

[0174] The characterization data of compound 14b are as follows: 1 H NMR (400MHz, CDCl3) δ = 6.15 (s, 1H), 3.59 (t, J = 5.5Hz, 2H), 3.41 (dd, J = 12.1, 6.1Hz, 2H), 1.71-1.62 (m, 2H), 1.20 (s, 9H);

[0175] 13 C NMR (100MHz, CDCl3) δ = 180.2, 59.3, 38.8, 36.3, 32.4, 27.7;

[0176] HR-MS(ESI)m / z calcd for:C8H 18 NO2[M+H] + 160.1332, found 160.1324.

[0177] Example 15: Electrochemical synthesis of compound 15b

[0178]

[0179] 15b was prepared from 15a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 1 in a yield of 52%.

[0180] The characterization data of compound 15b are as follows: 1 H NMR (400MHz, CDCl3) δ = 5.68 (s, 1H), 3.61 (t, J = 6.5Hz, 2H), 3.23 (dd, J = 13.1, 6.8Hz, 2H), 1.60-1.45 (m, 4H), 1.43-1.28 (m, 4H), 1.17 (s, 9H);

[0181] 13 C NMR (100MHz, CDCl3) δ = 178.7, 62.7, 39.4, 38.8, 32.6, 29.7, 27.7, 26.5, 25.3;

[0182] HR-MS(ESI)m / z calcd for:C 11 H 24 NO2[M+H] + 202.1802, found 202.1803.

[0183] Example 16: Electrochemical synthesis of compound 16b

[0184]

[0185] 16b was prepared from 16a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 1 in a yield of 56%.

[0186] The characterization data of compound 16b are as follows: 1 H NMR (400MHz, CDCl3) δ = 5.68 (s, 1H), 3.60 (t, J = 6.6Hz, 2H), 3.20 (dd, J = 13.1, 7.0Hz, 2H), 1.58-1.42 (m, 4H), 1.36-1.27 (m, 6H), 1.16 (s, 9H);

[0187] 13 C NMR (100MHz, CDCl3) δ = 178.6, 62.8, 39.6, 38.7, 32.7, 29.6, 29.1, 27.7, 26.9, 25.7;

[0188] HR-MS(ESI)m / z calcd for:C 12H 26 NO2[M+H] + 216.1958, found 216.1960.

[0189] Example 17: Electrochemical synthesis of compound 17b

[0190]

[0191] 17b was prepared from 17a (0.2 mmol) as a white solid according to the method and reaction conditions of Example 1 in a yield of 58%.

[0192] The characterization data of compound 17b are as follows: 1 H NMR (400MHz, CDCl3) δ = 6.94 (s, 1H), 3.65-3.55 (m, 2H), 3.47-3.37 (m, 1H), 3.10-3.01 (m, 1H), 2.24-2 .09(m,2H),1.80-1.67(m,2H),1.66-1.57(m,1H),1.56-1.43(m,1H),1.34-1.21(m,2H),1.16(s,9H);

[0193] 13 C NMR (100MHz, CDCl3) δ = 178.7, 63.4, 43.6, 41.5, 40.3, 38.7, 29.8, 28.1, 27.7, 23.1;

[0194] HR-MS(ESI)m / z calcd for:C 12 H 23 NO2Na + [M+Na] + 236.1621, found 236.1614.

[0195] Example 18: Electrochemical synthesis of compound 18b

[0196]

[0197] In a 30 mL single-chamber electrolytic cell, the raw material 1a (0.2 mmol), Cu(MeCN)4BF4 (0.04 mmol) and the electrolyte Bu4NHSO4 (0.2 mmol) were added to 4 mL of methanol. A graphite sheet electrode was used as the anode and a graphite sheet electrode as the cathode. Electrolysis was carried out at a constant current of 8 mA. After stirring at room temperature for 6 hours, the electrolysis was stopped. The reaction solution was transferred, concentrated, and purified by column chromatography to obtain 18b as a colorless liquid in a yield of 84%.

[0198] The characterization data of compound 18b are as follows: 1 H NMR (400MHz, CDCl3) δ = 5.73 (s, 1H), 4.31 (t, J = 5.7Hz, 1H), 3.27 (s, 6H), 3.19 (dd, J = 13 .0,6.9Hz,2H),1.61-1.53(m,2H),1.53-1.43(m,2H),1.38-1.29(m,2H),1.14(s,9H);

[0199] 13 C NMR (100MHz, CDCl3) δ = 178.5, 104.4, 52.8, 39.5, 38.7, 32.1, 29.4, 27.6, 21.9;

[0200] HR-MS(ESI)m / z calcd for:C 12 H 25 NO3Na + [M+Na] + 254.1727,found 254.1725.

[0201] Example 19: Electrochemical synthesis of compound 19b

[0202]

[0203] In a 30 mL single-chamber electrolytic cell, the raw material 1a (0.2 mmol), Cu(MeCN)4BF4 (0.04 mmol) and the electrolyte Bu4NHSO4 (0.2 mmol) were added to 4 mL of ethanol. A graphite sheet electrode was used as the anode and a graphite sheet electrode as the cathode. Electrolysis was carried out at a constant current of 8 mA. After stirring at room temperature for 6 hours, the electrolysis was stopped. The reaction solution was transferred, concentrated, and purified by column chromatography to obtain 19b as a colorless liquid in a yield of 70%.

[0204] The characterization data of compound 19b are as follows: 1 H NMR (400MHz, CDCl3) δ = 5.69 (s, 1H), 4.43 (t, J = 5.7Hz, 1H), 3.65-3.54 (m, 2H), 3.50-3.39 (m, 2H), 3.20 (dd,J=12.8,7.0Hz,2H),1.63-1.55(m,2H),1.54-1.44(m,2H),1.39-1.31(m,2H),1.18-1.13(m,15H);

[0205] 13C NMR (100MHz, CDCl3) δ = 178.5, 102.8, 61.2, 39.5, 38.7, 33.3, 29.5, 27.7, 22.1, 15.4;

[0206] HR-MS(ESI)m / z calcd for:C 14 H 29 NO3Na + [M+Na] + 282.2040,found 282.2036.

[0207] Example 20: Electrochemical synthesis of compound 22b

[0208]

[0209] In a 30 mL single-chamber electrolytic cell, the raw material 22a (0.2 mmol), Cu(MeCN)4BF4 (0.1 mmol) and the electrolyte Bu4NHSO4 (0.2 mmol) were added to a mixed solvent of 4 mL of acetone and water (volume ratio of 1:7). Electrolysis was carried out at a constant current of 12 mA using a graphite sheet electrode as the anode and a graphite sheet electrode as the cathode. The electrolysis was stopped after stirring at room temperature for 6 hours. The reaction solution was transferred, concentrated, and purified by column chromatography to obtain 22b as a colorless liquid in a yield of 52%.

[0210] The characterization data of compound 22b are as follows: 1 H NMR (400MHz, CDCl3) δ = 7.16 (d, J = 10.4Hz, 1H), 6.45 (d, J = 7.5Hz, 1H), 4.59-4.51 (m, 1H), 4.46 (dd, J = 8.6, 4.9Hz, 1H), 3.69 (s, 3H), 3.60 (t, J = 5.6H) z,2H),2.20-2.09(m,1H),1.97-1.84(m,1H),1.72-1.63(m,1H),1.65-1. 50(m,2H),1.47-1.36(m,2H),1.19(s,9H),0.90(dd,J=14.6,6.8Hz,6H);

[0211] 13 C NMR (100MHz, CDCl3) δ=179.0,172.3,62.3,57.4,52.7,52.3,38.9,32.3,32.1,31.1,27.5,21.9,19.2,17.8;

[0212] HR-MS(ESI)m / z calcd for:C 17 H32 N2O5Na + [M+Na] + 367.2204,found 367.2200.

[0213] Example 21: Electrochemical synthesis of compound 23b

[0214]

[0215] Using 23a (0.2 mmol) as starting material, according to the method and reaction conditions of Example 20, 23b was prepared as a white solid in a yield of 59%.

[0216] The characterization data of compound 23b are as follows: 1 HNMR (400MHz, CDCl3) δ = 7.26 (d, J = 8.2Hz, 1H), 6.49 (d, J = 7.9Hz, 1H), 4.57-4.49 (m, 2H), 3.68 (s, 3H), 3.60 (t, J =6.2Hz,2H),1.93-1.81(m,1H),1.71-1.49(m,6H),1.44-1.36(m,2H),1.18(s,9H),0.91(dd,J=6.1,4.7Hz,6H);

[0217] 13 C NMR (100MHz, CDCl3) δ=179.0,173.3,172.1,62.2,52.6,52.4,50.8,41.2,38.9,32.3,32.1,27.5,25.0,22.9,21.7;

[0218] HR-MS(ESI)m / z calcd for:C 18 H 34 N2O5Na + [M+Na] + 381.2360, found 381.2358.

[0219] Example 22: Electrochemical synthesis of compound 24b

[0220]

[0221] 24b was prepared from 24a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 69%.

[0222] The characterization data of compound 24b are as follows: 1HNMR (400MHz, CDCl3) δ = 7.07 (d, J = 8.7Hz, 1H), 6.39 (d, J = 8.0Hz, 1H), 4.56-4.47 (m, 2H), 3.70 (s, 3H), 3.62 (t, J = 6.2Hz, 2H), 1 .97-1.81(m,2H),1.74-1.52(m,3H),1.48-1.32(m,3H),1.30-1.19(m,1H),1.20(s,9H),1.18-1.11(m,1H),0.94-0.85(m,6H);

[0223] 13 C NMR (100MHz, CDCl3) δ=179.1,172.3,172.1,62.3,56.6,52.7,52.2,38.9,37.7,32.1,32.1,27.6,25.2,21.9,15.7,11.6;

[0224] HR-MS(ESI)m / z calcd for C 18 H 34 N2O5Na + [M+Na] + 381.2360, found 381.2354.

[0225] Example 23: Electrochemical synthesis of compound 25b

[0226]

[0227] Compound 25b was prepared from compound 25a as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 54%.

[0228] The characterization data of compound 25b are as follows: 1 HNMR (400MHz, CDCl3) δ = 6.77 (d, J = 9.1Hz, 1H), 6.40 (d, J = 7.7Hz, 1H), 4.60-4.51 (m, 1H), 4.43 (d, J = 9.2Hz, 1H), 4.22 (q, J = 6.2Hz, 1H), 3.69 (s, 3H), 3.64(t,J=6.3Hz,2H),1.97-1.88(m,1H),1.77-1.66(m,1H),1.66-1.55(m ,2H),1.50-1.39(m,2H),1.22(s,9H),1.15(d,J=6.2Hz,3H),1.09(s,9H);

[0229] 13C NMR (100MHz, CDCl3) δ=178.7,172.6,171.3,74.3,67.4,62.4,57.9,52.9,52.4,38.9,32.2,32.0,28.4,27.6,21.8,21.2;

[0230] HR-MS(ESI)m / z calcd for:C 20 H 39 N2O6[M+H] + 403.2803,found403.2804.

[0231] Example 24: Electrochemical synthesis of compound 26b

[0232]

[0233] 26b was prepared from 26a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 48%.

[0234] The characterization data of compound 26b are as follows: 1 HNMR (400MHz, CDCl3) δ = 7.05 (d, J = 8.5Hz, 1H), 6.49 (d, J = 7.9Hz, 1H), 4.64 (dt, J = 8.3, 3.2Hz, 1H), 4.57-4.48 (m, 1H), 3.77 (dd, J = 9.1, 3.2Hz, 1H), 3 .70(s,3H),3.59(t,J=6.3Hz,2H),3.53(dd,J=9.1,3.2Hz,1H),1.94-1.8 1(m,1H),1.73-1.47(m,3H),1.45-1.34(m,2H),1.19(s,9H),1.10(s,9H);

[0235] 13 C NMR (100MHz, CDCl3) δ = 178.8, 172.0, 170.9, 73.6, 62.2, 61.8, 53.0, 52.6, 52.5, 38.9, 32.1, 32.0, 27.6, 27.3, 21.7;

[0236] HR-MS(ESI)m / z calcd for C 19 H 36 N2O6Na + [M+Na] + 411.2466,found411.2456.

[0237] Example 25: Electrochemical synthesis of compound 27b

[0238]

[0239] Using raw material 27a (0.2 mmol) as raw material, according to the method and reaction conditions of Example 20, 27b was prepared as a colorless liquid with a yield of 51%.

[0240] The characterization data of compound 27b are as follows: 1 H NMR (400MHz, CDCl3) δ = 7.34-7.19 (m, 3H), 7.19-7.09 (m, 3H), 6.41 (d, J = 7.9Hz, 1H), 4.89-4.79 (m, 1H), 4.53-4.43 (m, 1H), 3.71 (s, 3H), 3.56 (t, J=6.2Hz,2H),3.19(dd,J=14.0,5.3Hz,1H),3.01(dd,J=14.0,8.0Hz,1H),1.79-1.66(m,1H),1.58-1.42(m,3H),1.31-1.19(m,2H),1.18(s,9H);

[0241] 13 C NMR (100MHz, CDCl3) δ=178.9,172.0,171.9,136.1,129.3,128.7,127.2,62.3,53.3,52.5,38.9,38.0,32.3,32.1,27.5,21.5;

[0242] HR-MS(ESI)m / z calcd for C 21 H 32 N2O5Na + [M+Na] + 415.2204, found 415.2194.

[0243] Example 26: Electrochemical synthesis of compound 28b

[0244]

[0245] 28b was prepared from 28a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 57%.

[0246] The characterization data of compound 28b are as follows: 1HNMR (400MHz, CDCl3) δ = 7.34 (d, J = 7.1Hz, 1H), 6.40 (d, J = 7.9Hz, 1H), 4.60-4.46 (m, 2H), 3.71 (s, 3H), 3.66 (s, 3H), 3.62 (t, J=6.2Hz,2H),2.44-2.33(m,2H),2.26-2.14(m,1H),2.06-1.82(m,2H),1.74-1.51(m,3H),1.47-1.36(m,2H),1.19(s,9H);

[0247] 13 C NMR (100MHz, CDCl3) δ=179.0,173.3,172.2,172.1,62.2,52.7,52.1,51.7,38.9,32.2,32.0,30.1,27.5,27.1,21.8;

[0248] HR-MS(ESI)m / z calcd for:C 18 H 33 N2O7[M+H] + 389.2282, found 389.2285.

[0249] Example 27: Electrochemical synthesis of compound 29b

[0250]

[0251] 29b was prepared from 29a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 33%.

[0252] The characterization data of compound 29b are as follows: 1 HNMR (400MHz, CDCl3) δ = 7.18 (d, J = 7.9Hz, 1H), 6.46 (d, J = 7.7Hz, 1H), 4.85 (t, J = 6.0Hz, 1H), 4.59-4.45 (m, 2H), 3.70 (s, 3H), 3.6 2(t,J=5.6Hz,2H),3.13-3.01(m,2H),1.95-1.77(m,2H),1.75-1.63(m,2H),1.61-1.54(m,2H),1.50-1.33(m,15H),1.19(s,9H);

[0253] 13C NMR (100MHz, CDCl3) δ=178.9,172.6,172.0,156.3,79.3,62.2,52.8,52.5,52.1,40.3,38.9,32.3,32.0,31.8,29.6,28.5,27.6,22.7,21.8;

[0254] HR-MS(ESI)m / z calcd for C 23 H 43 N3O7Na + [M+Na] + 496.2994, found 496.2987.

[0255] Example 28: Electrochemical synthesis of compound 30b

[0256]

[0257] 30b was prepared from 30a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 77%.

[0258] The characterization data of compound 30b are as follows: 1 HNMR (400MHz, CDCl3) δ = 7.12 (d, J = 8.0Hz, 1H), 6.43 (d, J = 7.8Hz, 1H), 5.73-5.59 (m, 1H), 5.16-5.06 (m, 2H), 4.65-4.55 (m, 1H), 4.55-4. 46(m,1H),3.70(s,3H),3.60(t,J=6.3Hz,2H),2.63-2.40(m,3H),1.94-1.79(m,1H),1.71-1.49(m,3H),1.45-1.34(m,2H),1.19(s,9H);

[0259] 13 C NMR (100MHz, CDCl3) δ=179.0,172.0,171.9,132.3,119.3,62.3,52.6,52.5,51.8,38.9,36.4,32.3,32.1,27.5,21.8;

[0260] HR-MS(ESI)m / z calcd for:C 17 H 31 N2O5[M+H] + 343.2227, found 343.2230.

[0261] Example 29: Electrochemical synthesis of compound 31b

[0262]

[0263] 31b was prepared from 31a (0.2 mmol) as a white solid according to the method and reaction conditions of Example 20 in a yield of 59%.

[0264] The characterization data of compound 31b are as follows: 1 HNMR (400MHz, CDCl3) δ = 7.48 (d, J = 8.6Hz, 1H), 6.53 (d, J = 7.8Hz, 1H), 4.53-4.43 (m, 1H), 3.68 (s, 3H), 3.60 (t, J = 6.2 Hz,2H),2.31-2.09(m,2H),2.00-1.88(m,2H),1.87-1.69(m,5H),1.67-1.50(m,3H),1.46-1.35(m,2H),1.17(s,9H);

[0265] 13 C NMR (100MHz, CDCl3) δ = 178.9, 174.6, 171.8, 66.0, 62.2, 52.6, 52.4, 38.8, 37.4, 37.1, 32.2, 32.1, 27.5, 24.6, 24.6, 21.4;

[0266] HR-MS(ESI)m / z calcd for C 18 H 32 N2O5Na + [M+Na] + 379.2203,found 379.2200.

[0267] Example 30: Electrochemical synthesis of compound 32b

[0268]

[0269] In a 30 mL single-chamber electrolytic cell, the raw material 32a (0.2 mmol), Cu(MeCN)4BF4 (0.1 mmol) and the electrolyte Bu4NHSO4 (0.2 mmol) were added to a mixed solvent of 4 mL of acetone and water (volume ratio of 1:7). Electrolysis was carried out at a constant current of 20 mA using a graphite sheet electrode as the anode and a graphite sheet electrode as the cathode. The electrolysis was stopped after stirring at room temperature for 4 hours. The reaction solution was transferred, concentrated, and purified by column chromatography to obtain 32b as a white solid in a yield of 50%.

[0270] The characterization data of compound 32b are as follows:1 HNMR (400MHz, CDCl3) δ = 7.19 (d, J = 7.8Hz, 1H), 6.61 (d, J = 7.5Hz, 1H), 4.67-4.59 (m, 1H), 4.56-4.47 (m, 1H), 3. 78-3.66(m,5H),1.99-1.90(m,1H),1.85-1.77(m,1H),1.75-1.53(m,5H),1.20(s,9H),0.91(t,J=6.1Hz,6H);

[0271] 13 C NMR (100MHz, CDCl3) δ=178.9,173.5,172.1,62.8,52.5,52.3,51.1,41.0,38.9,30.5,27.64,27.56,24.9,22.9,21.8;

[0272] HR-MS(ESI)m / z calcd for C 17 H 32 N2O5Na + [M+Na] + 367.2203, found 367.2196.

[0273] Example 31: Electrochemical synthesis of compound 33b

[0274]

[0275] 33b was prepared from 33a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 30 in a yield of 51%.

[0276] The characterization data of compound 33b are as follows: 1 HNMR (400MHz, CDCl3) δ = 7.45 (d, J = 7.5Hz, 1H), 6.67 (d, J = 7.6Hz, 1H), 4.69-4.60 (m, 1H), 4.56-4.46 ( m,1H),3.76-3.69(m,5H),1.98-1.77(m,2H),1.74-1.57(m,2H),1.40(d,J=7.3Hz,3H),1.19(s,9H);

[0277] 13 C NMR (100MHz, CDCl3) δ=179.0,173.5,171.9,62.6,52.6,52.3,48.2,38.9,30.7,27.61,27.56,17.8;

[0278] HR-MS(ESI)m / z calcd for:C 14 H 27 N2O5[M+H] + 303.1914, found 303.1916.

[0279] Example 32: Electrochemical synthesis of compound 34b

[0280]

[0281] 34b was prepared from 34a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 30 in a yield of 59%.

[0282] The characterization data of compound 34b are as follows: 1 HNMR (400MHz, CDCl3) δ = 6.96 (d, J = 9.1Hz, 1H), 6.65 (d, J = 7.7Hz, 1H), 4.71-4.62 (m, 1H), 4.45 (dd, J = 9.0, 1.8Hz, 1H), 4.50-4.40 (m ,1H),3.77-3.67(m,5H),2.02-1.93(m,1H),1.89-1.78(m,1H),1.74-1.60(m,2H),1.20(s,9H),1.16(d,J=6.2Hz,3H),1.10(s,9H);

[0283] 13 C NMR (100MHz, CDCl3) δ = 178.6, 172.6, 171.3, 74.4, 67.4, 62.6, 58.1, 52.6, 52.4, 38.9, 30.5, 28.4, 27.9, 27.6, 21.2;

[0284] HR-MS(ESI)m / z calcd for C 19 H 36 N2O6Na + [M+Na] + 411.2466,found411.2463.

[0285] Example 33: Electrochemical synthesis of compound 35b

[0286]

[0287] 35b was prepared from 35a (0.2 mmol) as a white solid in 64% yield according to the method and reaction conditions of Example 30.

[0288] The characterization data of compound 35b are as follows: 1 H NMR (400MHz, CDCl3) δ = 7.57 (s, 1H), 6.72 (d, J = 7.7Hz, 1H), 4.63-4.52 (m, 1H), 3.74-3.65 (m, 5 H),2.33-2.08(m,2H),1.99-1.85(m,3H),1.85-1.67(m,5H),1.69-1.54(m,2H),1.18(s,9H);

[0289] 13 C NMR (100MHz, CDCl3) δ=179.0,174.6,171.7,66.0,62.5,52.6,52.1,38.9,37.5,37.1,30.3,27.6,27.5,24.61,24.57;

[0290] HR-MS(ESI)m / z calcd for:C 17 H 31 N2O5[M+H] + 343.2227, found 343.2229.

[0291] Example 34: Electrochemical synthesis of compound 36b

[0292]

[0293] 36b was prepared from 36a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 60%.

[0294] The characterization data of compound 36b are as follows: 1 HNMR (400MHz, CDCl3) δ = 7.55 (t, J = 7.6Hz, 1H), 7.44 (d, J = 5.6Hz, 1H), 6.59 (d, J =6.2Hz,1H),4.58-4.47(m,1H),4.41-4.32(m,1H),4.04(dd,J=17.9,5.7Hz,1H) ,3.88(dd,J=17.9,5.3Hz,1H),3.70(s,3H),3.60(t,J=6.1Hz,2H),1.89-1.78(m ,1H),1.73-1.52(m,3H),1.48-1.40(m,2H),1.37(d,J=7.1Hz,3H),1.17(s,9H);

[0295] 13C NMR (100MHz, CDCl3) δ = 179.6, 172.8, 172.5, 170.5, 62.1, 53.6, 52.4, 49.0, 41.2, 38.8, 32.0, 31.9, 27.5, 22.0, 17.8;

[0296] HR-MS(ESI)m / z calcd for C 17 H 31 N3O6Na + [M+Na] + 396.2106, found 396.2100.

[0297] Example 35: Electrochemical synthesis of compound 37b

[0298]

[0299] 37b was prepared from 37a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 54%.

[0300] The characterization data of compound 37b are as follows: 1 H NMR (400MHz, CDCl3) δ=7.32-7.17(m,4H),7.16-7.08(m,2H),6.94(d,J=7.8Hz,1H),6.51(d,J=7.4Hz,1H),4.82-4.73(m,1H),4.50-4.38(m,2H),3 .69(s,3H),3.61(t,J=5.7Hz,2H),3.18-3.02(m,2H),1.91-1.79(m,1H), 1.74-1.49(m,3H),1.46-1.37(m,2H),1.31(d,J=7.1Hz,3H),1.20(s,9H);

[0301] 13 C NMR(100MHz, CDCl3)δ=179.2,172.1,171.9,171.9,136.1,129.4,128.6,12 7.2,62.2,53.6,53.1,52.5,49.1,38.8,37.8,32.3,32.0,27.5,21.9,18.1;

[0302] HR-MS(ESI)m / z calcd for C 24 H 37 N3O6Na + [M+Na] +486.2575, found 486.2567.

[0303] Example 36: Electrochemical synthesis of compound 38b

[0304]

[0305] 38b was prepared from 38a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 52%.

[0306] The characterization data of compound 38b are as follows: 1 HNMR(400MHz, CDCl3)δ=7.42(d,J=7.5Hz,1H),7.27(d,J=9.0Hz,1H),6.61(d,J=7.2H z,1H),4.55-4.47(m,1H),4.46-4.37(m,2H),3.69(s,3H),3.64(s,3H),3.59(t,J=7. 2Hz,2H),2.37(t,J=8.0Hz,2H),2.24-2.12(m,1H),2.06-1.94(m,1H),1.90-1.78(m, 1H),1.74-1.50(m,6H),1.46-1.35(m,2H),1.17(s,9H),0.89(dd,J=14.2,5.6Hz,6H);

[0307] 13 C NMR (100MHz, CDCl3) δ = 179.3, 173.4, 172.7, 172.3, 172.1, 62.1, 53.3, 52.5, 52. 0,52.0,51.7,40.6,38.8,32.1,32.0,30.2,27.5,26.9,24.8,23.1,21.9,21.8;

[0308] HR-MS(ESI)m / z calcd for C 24 H 43 N3O8Na + [M+Na] + 524.2942, found 524.2943.

[0309] Example 37: Electrochemical synthesis of compound 39b

[0310]

[0311] Compound 39b was prepared from 39a (0.2 mmol) according to the method and reaction conditions of Example 20 as a colorless liquid in a yield of 52%.

[0312] The characterization data of compound 39b are as follows: 1 HNMR (400MHz, CDCl3) δ = 7.35 (d, J = 8.1Hz, 1H), 6.95 (d, J = 7.9Hz, 1H), 6.52 (d, J = 7.7Hz,1H),5.72-5.58(m,1H),5.13-5.02(m,2H),4.60-4.52(m,1H),4.48-4.37( m,2H),3.70(s,3H),3.60(t,J=5.9Hz,2H),2.59-2.46(m,2H),1.90-1.79(m,1H), 1.72-1.50(m,6H),1.44-1.37(m,2H),1.19(s,9H),0.90(dd,J=13.2,5.8Hz,6H);

[0313] 13 C NMR (100MHz, CDCl3)δ=179.2,172.6,172.0,171.9,132.3,119.2,62.3,53 .2,52.4,52.0,40.6,38.9,36.3,32.5,32.1,27.5,24.9,23.1,21.9,21.8;

[0314] HR-MS(ESI)m / z calcd for C 23 H 41 N3O6Na + [M+Na] + 478.2888, found 478.2881.

[0315] Example 38: Electrochemical synthesis of compound 40b

[0316]

[0317] Compound 40b was prepared from 40a (0.2 mmol) as a white solid according to the method and reaction conditions of Example 20 in a yield of 52%.

[0318] The characterization data of compound 40b are as follows: 1HNMR (400MHz, CDCl3) δ = 7.67 (d, J = 8.6Hz, 1H), 7.60 (d, J = 7.4Hz, 1H), 7.20 (d, J = 7.9Hz, 1H), 6.60(d,J=7.0Hz,1H),5.78-5.64(m,1H),5.15-5.02(m,2H),4.79-4.64(m,1H),4.65-4.41( m,3H),3.70(s,3H),3.59(t,J=6.2Hz,2H),2.61-2.40(m,2H),1.89-1.77(m,1H),1.72-1.49 (m,6H),1.44-1.36(m,2H),1.31(d,J=6.9Hz,3H),1.18(s,9H),0.91(dd,J=7.6,5.6Hz,6H);

[0319] 13 C NMR (100MHz, CDCl3) δ=179.0,172.4,172.3,172.0,171.7,132.5,119.0,62.3,53.1,52 .4,52.2,51.9,48.7,41.6,38.8,36.3,33.0,32.1,27.5,24.9,23.1,22.0,21.7,18.6;

[0320] HR-MS(ESI)m / z calcd for C 26 H 46 N4O7Na + [M+Na] + 549.3259, found 549.3256.

[0321] Example 39: Electrochemical synthesis of compound 41b

[0322]

[0323] Using 41a (0.2 mmol) as starting material, according to the method and reaction conditions of Example 20, 41b was prepared as a colorless liquid in a yield of 47%.

[0324] The characterization data of compound 41b are as follows: 1HNMR (400MHz, CDCl3) δ = 7.08 (t, J = 6.0Hz, 1H), 6.47 (d, J = 7.8Hz, 1H), 4.46- 4.37(m,1H),3.65(s,3H),3.60(t,J=6.2Hz,2H),3.37-3.03(m,2H),2.25(d, J=6.7Hz,2H),2.17-2.05(m,1H),1.89-1.75(m,1H),1.70-1.50(m,4H),1.4 4-1.35(m,2H),1.18(s,9H),1.17-1.04(m,2H),0.86(dd,J=9.3,6.6Hz,6H);

[0325] 13 C NMR (100MHz, CDCl3) δ=178.9,173.8,172.4,62.2,53.0,51.8,42.9,41.6,38.9,37.3,33.2,32.5,32.1,27.6,25.2,22.8,22.7,21.9;

[0326] HR-MS(ESI)m / z calcd for:C 20 H 39 N2O5[M+H] + 387.2853, found 387.2847.

[0327] Example 40: Electrochemical synthesis of compound 42b

[0328]

[0329] Compound 42b was prepared from 42a (0.2 mmol) as a white solid according to the method and reaction conditions of Example 20 in a yield of 69%.

[0330] The characterization data of compound 42b are as follows: 1 HNMR (400MHz, CDCl3) δ = 6.47 (d, J = 7.8Hz, 1H), 6.19 (s, 1H), 4.35-4.27 (m, 1H), 3.61 (t, J = 6.3Hz, 2H), 2.09-2.03 (m ,3H),1.99-1.93(m,6H),1.84-1.73(m,1H),1.68-1.63(m,6H),1.62-1.51(m,3H),1.43-1.32(m,2H),1.18(s,9H);

[0331] 13C NMR (100MHz, CDCl3) δ = 178.7, 171.0, 62.3, 53.2, 52.2, 41.6, 38.8, 36.4, 32.6, 32.2, 29.5, 27.6, 21.7;

[0332] HR-MS(ESI)m / z calcd for C 21 H 36 N2O3Na + [M+Na] + 387.2618, found 387.2615.

[0333] Example 41: Electrochemical synthesis of compound 43b

[0334]

[0335] Compound 43b was prepared from 43a (0.2 mmol) according to the method and reaction conditions of Example 20 as a colorless liquid in a yield of 45%.

[0336] The characterization data of compound 43b are as follows: 1 HNMR(400MHz, CDCl3)δ=7.44(t,J=5.9Hz,1H),6.59(d,J=7.8Hz,1H),5.33(t,J=5.9Hz,1H),4.47-4.36(m,1H),3 .60(t,J=6.5Hz,2H),3.45-3.19(m,4H),1.88-1.74(m,1H),1.73-1.49(m,3H),1.46-1.37(m,11H),1.18(s,9H);

[0337] 13 C NMR (100MHz, CDCl3) δ=179.0,172.8,156.7,79.7,62.1,53.0,40.4,40.1,38.8,32.6,31.9,28.5,27.6,21.8;

[0338] HR-MS(ESI)m / z calcd for C 18 H 35 N3O5Na + [M+Na] + 396.2469, found 396.2465.

[0339] Example 42: Electrochemical synthesis of compound 44b

[0340]

[0341] Compound 44b was prepared from 44a (0.2 mmol) according to the method and reaction conditions of Example 20 as a colorless liquid in a yield of 61%.

[0342] The characterization data of compound 44b are as follows: 1 HNMR(400MHz, CDCl3)δ=6.17(d,J=7.5Hz,1H),4.60-4.52(m,1H),4.44-4.36(m,1H),4.31-4.23(m,1H),3.62(t,J=6.1H z,2H),2.74(t,J=6.2Hz,2H),1.94-1.84(m,1H),1.80-1.69(m,1H),1.64-1.52(m,2H),1.49-1.38(m,2H),1.20(s,9H);

[0343] 13 C NMR (100MHz, CDCl3) δ = 178.8, 172.4, 116.8, 62.2, 59.5, 52.2, 38.8, 32.0, 27.5, 21.8, 18.1;

[0344] HR-MS(ESI)m / z calcd for C 14 H 24 N2O4Na + [M+Na] + 307.1629, found 307.1622.

[0345] Example 43: Electrochemical synthesis of compound 45b

[0346]

[0347] Compound 45b was prepared from 45a (0.2 mmol) as a colorless liquid according to the method and reaction conditions of Example 20 in a yield of 47%.

[0348] The characterization data of compound 45b are as follows: 1 HNMR (400MHz, CDCl3) δ = 6.23 (d, J = 7.7Hz, 1H), 4.96 (d, J = 13.3Hz, 2H), 4.68-4.47 (m, 3H), 3.67- 3.56(m,2H),1.91-1.84(m,1H),1.75(s,3H),1.75-1.50(m,3H),1.48-1.35(m,2H),1.20(s,9H);

[0349] 13C NMR (100MHz, CDCl3) δ = 178.6, 172.7, 139.4, 113.8, 68.8, 62.4, 52.0, 38.9, 32.5, 32.1, 27.6, 21.6, 19.6;

[0350] HR-MS(ESI)m / z calcd for C 15 H 27 NO4Na + [M+Na] + 308.1832, found 308.1827.

[0351] Example 44 Reaction effect of compound 1a under different conditions

[0352] (1) Different additives shown in Table 1 were added to the electrolyte, and compound 1b was prepared according to the method of Example 1. The yields are shown in Table 1.

[0353]

[0354] Table 1

[0355]

[0356]

[0357] (2) Compound 1b was prepared according to the method of Example 1 using different solvents shown in Table 2. The yields are shown in Table 2.

[0358]

[0359] Table 2

[0360]

[0361] (3) Compound 1b was prepared according to the method of Example 1 using different electrodes and electrolytes shown in Table 3. The yields are shown in Table 3.

[0362]

[0363] Table 3

[0364]

[0365]

[0366] Note: C = graphite flake, RVC = reticulated glassy carbon.

[0367] (4) Compound 1b was prepared according to the method of Example 1 using different currents shown in Table 4. The yields are shown in Table 4.

[0368]

[0369]

[0370] Example 45 Reaction effect of compound 23a under different conditions

[0371] Compound 23b was prepared according to the method of Example 21 under the conditions shown in Table 5. The yield is shown in Table 5.

[0372]

[0373] Table 5

[0374]

[0375] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A method for synthesizing a distal amino alcohol compound, characterized in that: The steps include: Electrolyzing the cyclic amine compound represented by formula (I) to obtain the distal amino alcohol compound represented by formula (II), Among them, R 1 Selected from: aryl, arylformyl, alkylacyl; Each R 2 are independently selected from: hydrogen, alkoxy, halogen, aryl, alkyl, alkoxycarbonyl, or two adjacent R 2 Together with the carbon atom to which it is attached, it forms a cycloalkyl group; R is selected from: hydrogen, alkoxy, halogen, aryl, alkyl, Each R 3 are independently selected from: amino acids or their esters after removing an amino hydrogen, dipeptides or their esters after removing an amino hydrogen, tripeptides or their esters after removing an amino hydrogen, R 4 Substituted or unsubstituted alkylamino, R 4 Substituted or unsubstituted cycloalkylamino, R 4 Substituted or unsubstituted alkoxy, R 4 a substituted or unsubstituted cycloalkoxy group; Each R 4 Each of the following groups is independently selected from the group consisting of amino, protected amino, cyano, alkenyl, and alkoxycarbonyl; R 5 Selected from: hydrogen, methyl, ethyl; R 6 Selected from: hydrogen, methoxy, ethoxy; n is selected from: 0, 1, 2, 3, 4; m is selected from: 0, 1, 2, 3, 4, 5, 6; The electrolysis is carried out in a single-chamber electrolytic cell containing an electrolyte; The solvent in the electrolyte is water, methanol, ethanol, acetone, or a mixed solvent of acetone and water; A copper compound is added to the electrolyte, and the copper compound is one or more of tetraacetonitrile copper tetrafluoroborate, tetraacetonitrile copper hexafluorophosphate, copper trifluoromethanesulfonate, cupric chloride, cuprous chloride, copper bromide and cuprous iodide; The anode for electrolysis is a graphite sheet or carbon felt, and the cathode is a graphite sheet, carbon felt, platinum sheet or copper sheet; The electrolysis is performed using a constant current with a current intensity of 4 mA to 30 mA, and an amount of electricity passed based on the amount of the cyclic amine compound is 4.5 F / mol to 34 F / mol.

2. The method for synthesizing a distal amino alcohol compound according to claim 1, wherein: The cyclic amine compound has a structure shown in the following formula (III): The distal amino alcohol compound has a structure shown in the following formula (IV): n is selected from: 0, 1, 2, 3, 4; m is selected from: 0, 1, 2, 3.

3. The method for synthesizing a distal amino alcohol compound according to claim 1, wherein: The cyclic amine compound has a structure shown in the following formula (V): The distal amino alcohol compound has a structure shown in the following formula (VI): n is selected from: 1, 2, 3.

4. The method for synthesizing the distal amino alcohol compound according to any one of claims 1 to 3, characterized in that: R 1 Selected from: C6-C 10 Aryl, C6-C 10 Arylformyl, C1-C 12 Alkyl acyl.

5. The method for synthesizing the distal amino alcohol compound according to claim 4, characterized in that: R 1 Selected from: phenyl, benzoyl, C1-C6 alkyl acyl.

6. The method for synthesizing the distal amino alcohol compound according to claim 5, characterized in that: R 1 Selected from: phenyl, benzoyl, pivaloyl.

7. The method for synthesizing a distal amino alcohol compound according to claim 1 or 2, characterized in that: Each R 2 are independently selected from: hydrogen, C1-C 12 Alkoxy, halogen, C6-C 10 Aryl, C1-C 12 Alkyl, C1-C 12 Alkoxycarbonyl, or two adjacent R 2 Together with the carbon atom it is connected to, it forms a C3-C 12 Cycloalkyl.

8. The method for synthesizing a distal amino alcohol compound according to claim 7, wherein: Each R 2 are independently selected from: hydrogen, C1-C6 alkoxy, halogen, C6-C 10 Aryl, C1-C6 alkyl, C1-C6 alkoxycarbonyl, or two adjacent R 2 Together with the carbon atom to which it is attached, it forms a C3-C8 cycloalkyl group.

9. The method for synthesizing a distal amino alcohol compound according to claim 8, wherein: Each R 2 are independently selected from: hydrogen, C1-C3 alkoxy, halogen, phenyl, C1-C3 alkyl, C1-C3 alkoxycarbonyl, or two adjacent R 2 Together with the carbon atom to which it is attached, it forms a C3-C6 cycloalkyl group.

10. The method for synthesizing a distal amino alcohol compound according to claim 9, characterized in that: Each R 2 are independently selected from: hydrogen, methoxy, fluorine, phenyl, chlorine, methyl, methoxycarbonyl, or two adjacent R 2 Together with the carbon atom to which it is connected, it forms a cyclopropyl or cyclopentyl group.

11. The method for synthesizing a distal amino alcohol compound according to claim 1 or 3, characterized in that: R is selected from: hydrogen, C1-C 12 Alkoxy, halogen, C6-C 10 Aryl, C1-C 12 alkyl, Each R 3 are independently selected from: amino acids or their esters after removing an amino hydrogen, dipeptides or their esters after removing an amino hydrogen, tripeptides or their esters after removing an amino hydrogen, R 4 Substituted or unsubstituted C1-C 12 Alkylamino, R 4 Substituted or unsubstituted C3-C 12 Cycloalkylamino, R 4 Substituted or unsubstituted C1-C 12 Alkoxy, R 4 Substituted or unsubstituted C3-C 12 cycloalkoxy; Each R 4 Each independently selected from: amino, protected amino, cyano, alkenyl, C1-C 12 Alkoxycarbonyl.

12. The method for synthesizing a distal amino alcohol compound according to claim 11, characterized in that: R is selected from: hydrogen, methoxy, fluorine, phenyl, chlorine, methyl, methoxycarbonyl, or a group selected from the following structures:

13. The method for synthesizing a distal amino alcohol compound according to claim 1, wherein: The cyclic amine compound is selected from the following compounds: The distal amino alcohol compound is selected from the following compounds:

14. The method for synthesizing a distal amino alcohol compound according to any one of claims 1 to 3, characterized in that: The electrolyte in the electrolyte solution is one or more of tetrabutylammonium hydrogen sulfate, ammonium sulfate and tetrabutylammonium perchlorate.

15. The method for synthesizing a distal amino alcohol compound according to any one of claims 1 to 3, characterized in that: The volume ratio of acetone to water in the mixed solvent of acetone and water is 1:1-8.

16. The method for synthesizing a distal amino alcohol compound according to any one of claims 1 to 3, characterized in that: The volume ratio of acetone to water in the mixed solvent of acetone and water is 1:6-8.

17. The method for synthesizing a distal amino alcohol compound according to any one of claims 1 to 3, characterized in that: R 5 and R 6 are all hydrogen, and the solvent in the electrolyte is water, or a mixed solvent of acetone and water; or, R 5 is methyl, R 6 is a methoxy group, and the solvent in the electrolyte is methanol; or R 5 is ethyl, R 6 The solvent in the electrolyte is ethanol.

18. The method for synthesizing a distal amino alcohol compound according to claim 14, wherein: The molar ratio of the cyclic amine compound to the electrolyte is 1:0.5-1.5; and / or, The molar concentration of the electrolyte in the electrolyte solution is 0.02 mmol / mL-0.08 mmol / mL; and / or, The molar ratio of the cyclic amine compound to the copper compound is 1:0.1-0.8; and / or, The molar concentration of the copper compound in the electrolyte is 0.004 mmol / mL-0.04 mmol / mL; and / or, The temperature of the electrolysis is 20°C-30°C.

19. The method for synthesizing a distal amino alcohol compound according to claim 18, wherein: The molar ratio of the cyclic amine compound to the electrolyte is 1:0.8-1.

2.

20. The method for synthesizing a distal amino alcohol compound according to claim 18, wherein: The molar concentration of the electrolyte in the electrolyte solution is 0.04 mmol / mL-0.06 mmol / mL.

21. The method for synthesizing a distal amino alcohol compound according to claim 18, wherein: The molar ratio of the cyclic amine compound to the copper compound is 1:0.2-0.

5.

22. The method for synthesizing a distal amino alcohol compound according to any one of claims 1 to 3, characterized in that: The current intensity is 8 mA to 20 mA, and the amount of current applied is 8.9 F / mol to 22.5 F / mol based on the amount of the cyclic amine compound.

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