Chiral brominated cyclic compound and method for electrochemically preparing chiral brominated cyclic compound

Abstract

The present application belongs to the technical field of organic synthesis, and in particular, relates to a chiral bromocyclic compound and a method for preparing a chiral bromocyclic compound by electrochemical method. The method comprises the steps of: adding a heteroatom-containing olefin compound, a chiral phosphoric acid catalyst, a phase transfer catalyst, an ionic bromide and an electrolyte to a non-separated electrolytic cell comprising a cathode and an anode, and performing an electrochemical reaction in an alkaline buffer solution to obtain a chiral bromocyclic compound. The electrochemical method for preparing a chiral bromocyclic compound provided by the present application uses electric current as an oxidant to replace traditional liquid bromine or bromine adducts as an oxidant, generates bromine in situ by an electrochemical method, and avoids the corrosiveness and difficult operation of liquid bromine; using a catalytic amount of a phase transfer catalyst under the action of electric current can achieve an excellent capture effect on bromine, and compared with the traditional method that requires more than one equivalent of a phase transfer reagent, the manufacturing cost of the chiral bromocyclic compound is reduced, thereby realizing a green and efficient conversion process.

Description

Technical Field

[0001] The present application belongs to the technical field of organic synthesis, and in particular relates to a chiral bromocyclic compound and a method for electrochemically preparing a chiral bromocyclic compound. Background Art

[0002] Chiral brominated cyclocompounds such as chiral cyclotryptamine derivatives play a very important role in the preparation of natural products, and chiral brominated cyclocompounds such as chiral bromooxazolines are also widely used in the synthesis of ligands. There are literature reports on the preparation of chiral brominated cyclocompounds such as chiral cyclotryptamine derivatives by tryptamine derivatives. In addition, there are also literature reports on the preparation of chiral brominated cyclocompounds such as chiral bromooxazolines by alkenyl-containing aromatic amides. However, the methods for preparing chiral brominated cyclocompounds reported in the prior art all use more than one equivalent of bromine adducts as phase transfer reagents, which require additional preparation, have high cost of use, and are highly corrosive and difficult to operate. Summary of the invention

[0003] The purpose of the present application is to provide a chiral bromocyclic compound and a method for electrochemically preparing a chiral bromocyclic compound, which aims to solve the problem that the existing method for preparing chiral bromocyclic compounds requires the use of more than one equivalent of bromine adduct as a phase transfer reagent, which has high preparation cost and great difficulty.

[0004] In order to achieve the above application purpose, the technical solution adopted in this application is as follows:

[0005] In a first aspect, the present application provides a method for electrochemically preparing a chiral brominated cyclic compound, comprising the following steps:

[0006] S10. In a non-separated electrolytic cell comprising a cathode and an anode, an olefin compound containing a heteroatom, a chiral phosphoric acid catalyst, a phase transfer catalyst, an ionic bromide and an electrolyte are added, and an electrochemical reaction is carried out in an alkaline buffer solution to obtain a chiral brominated cyclic compound;

[0007] Wherein, the structural formula of the heteroatom-containing olefin compound is The chiral bromocyclic compound has the general structural formula: X is selected from one heteroatom selected from N, O, S, and P, and R is selected from one heteroatom selected from fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, carboxyl, alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, mercapto, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkylester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy, and cycloalkylalkyl.

[0008] The first aspect of the present application provides a method for electrochemically preparing a chiral brominated cyclic compound, wherein an electrochemical reaction is carried out in an alkaline buffer solution, Br- The anode in the water phase is oxidized to generate elemental bromine, which can be combined with a phase transfer catalyst (PTC) dissolved in water to generate PTC-Br2. The counter anion Br - It can exchange anions with chiral phosphoric acid catalyst (CPA) in organic phase to generate PTC-Br2-CPA which is soluble in organic phase. The chiral bromine reagent can convert heteroatom-containing olefin compounds into chiral bromocyclic compounds, and the generated PTC-CPA can react with Br2 in aqueous phase to form PTC-Br2-CPA. - Negative ion exchange occurs to regenerate PTC soluble in water and CPA soluble in organic phase, thus entering a new catalytic cycle. The electrochemical method for preparing chiral bromocyclic compounds in the present application uses electric current as an oxidant instead of traditional liquid bromine or bromine adducts as an oxidant, and generates bromine in situ through electrochemical methods, which not only avoids the corrosiveness and difficult operation of liquid bromine; but also uses a catalytic amount of phase transfer catalyst (PTC) under the action of electric current to achieve excellent capture effect on bromine. Compared with the traditional method that requires more than one equivalent of PTC-Br2 phase transfer reagent, the manufacturing cost of chiral bromocyclic compounds is greatly reduced, thereby realizing a green and efficient conversion process and improving the preparation efficiency of chiral bromocyclic compounds.

[0009] In a second aspect, the present application provides an electrochemically prepared chiral brominated cyclic compound prepared by the above method, wherein the chiral brominated cyclic compound has the general structural formula: X is selected from one heteroatom selected from N, O, S, and P, and R is selected from one heteroatom selected from fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, carboxyl, alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, mercapto, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkylester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy, and cycloalkylalkyl.

[0010] The chiral bromocyclic compound provided in the second aspect of the present application is prepared by the above electrochemical method, which greatly reduces the manufacturing cost of the chiral bromocyclic compound, realizes a green and efficient conversion process, and broadens the types of chiral bromocyclic compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0012] Figure 1It is a schematic diagram of the mechanism of the method for electrochemical preparation of chiral brominated cyclic compounds provided in the examples of the present application. DETAILED DESCRIPTION

[0013] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application more clearly understood, the present application is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0014] In this application, the term "and / or" describes the association relationship of associated objects, indicating that there may be three relationships. For example, A and / or B can mean: A exists alone, A and B exist at the same time, and B exists alone. A and B can be singular or plural. The character " / " generally indicates that the associated objects are in an "or" relationship.

[0015] In this application, "at least one" means one or more, and "plurality" means two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single items or plural items. For example, "at least one of a, b or c", or "at least one of a, b and c", can all represent: a, b, c, ab (i.e. a and b), ac, bc, or abc, where a, b, c can be single or multiple, respectively.

[0016] It should be understood that in the various embodiments of the present application, the size of the serial numbers of the above-mentioned processes does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0017] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit the present application. The singular forms "a", "an" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings.

[0018] The weight of the relevant components mentioned in the embodiments of the present specification can not only refer to the specific content of each component, but also represent the proportional relationship between the weights of the components. Therefore, as long as the content of the relevant components in the embodiments of the present specification is proportionally enlarged or reduced, it is within the scope disclosed in the embodiments of the present specification. Specifically, the mass described in the embodiments of the present specification can be μg, mg, g, kg and other mass units known in the chemical industry.

[0019] The terms "first" and "second" are used only for descriptive purposes to distinguish objects such as substances from each other, and should not be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features. For example, without departing from the scope of the embodiments of the present application, the first XX may also be referred to as the second XX, and similarly, the second XX may also be referred to as the first XX. Thus, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features.

[0020] The first aspect of the embodiment of the present application provides a method for electrochemically preparing a chiral brominated cyclic compound, comprising the following steps:

[0021] S10. In a non-separated electrolytic cell comprising a cathode and an anode, an olefin compound containing a heteroatom, a chiral phosphoric acid catalyst, a phase transfer catalyst, an ionic bromide and an electrolyte are added, and an electrochemical reaction is carried out in an alkaline buffer solution to obtain a chiral brominated cyclic compound;

[0022] Wherein, the structural formula of the heteroatom-containing olefin compound is The chiral bromocyclic compound has the general structural formula: X is selected from one heteroatom selected from N, O, S, and P, and R is selected from one heteroatom selected from fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, carboxyl, alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, mercapto, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkylester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy, and cycloalkylalkyl.

[0023] The first aspect of the embodiment of the present application provides a method for electrochemically preparing a chiral brominated cyclic compound, wherein an olefin compound containing a heteroatom, a chiral phosphoric acid catalyst, a phase transfer catalyst, an ionic bromide and an electrolyte are added to a non-separated electrolytic cell comprising a cathode and an anode, and an electrochemical reaction is carried out in an alkaline buffer solution, wherein Br - The anode in the water phase is oxidized to generate elemental bromine, which can be combined with a phase transfer catalyst (PTC) dissolved in water to generate PTC-Br2. The counter anion Br - It can exchange anions with the chiral phosphoric acid catalyst (CPA) in the organic phase to generate PTC-Br2-CPA that is soluble in the organic phase. The chiral bromine reagent can convert heteroatom-containing olefin compounds into chiral bromocyclic compounds, and the generated PTC-CPA can react with Br2 in the aqueous phase to form a chiral bromocyclic compound. -Negative ion exchange occurs to regenerate PTC soluble in water and CPA soluble in organic phase, thus entering a new catalytic cycle. The electrochemical method for preparing chiral bromocyclic compounds in the embodiment of the present application uses electric current as an oxidant instead of traditional liquid bromine or bromine adducts as an oxidant, and generates bromine in situ through an electrochemical method, which not only avoids the corrosiveness and difficult operation of liquid bromine; but also uses a catalytic amount of phase transfer catalyst (PTC) under the action of electric current to achieve excellent capture effect on bromine. Compared with the traditional method that requires more than one equivalent of PTC-Br2 phase transfer reagent, the manufacturing cost of chiral bromocyclic compounds is greatly reduced, thereby realizing a green and efficient conversion process and improving the preparation efficiency of chiral bromocyclic compounds.

[0024] In some embodiments, in the electrochemical reaction system, the molar concentration of the chiral phosphoric acid catalyst is 0.01-50 mol%, the molar concentration of the phase transfer catalyst is 0.01-50 mol%, the concentration of the heteroatom-containing olefin compound is 0.01-1.0 mol / L, the concentration of the ionic bromide is 0.02-5.0 mol / L, and the concentration of the electrolyte is 0.02-5.0 mol / L. In this case, the concentrations of the heteroatom-containing olefin compound, the chiral phosphoric acid catalyst, the phase transfer catalyst, the ionic bromide and the electrolyte in the electrochemical reaction system effectively ensure sufficient contact reaction between the components, thereby ensuring the efficiency of converting the heteroatom-containing olefin compound into the chiral brominated cyclic compound.

[0025] In some embodiments, the temperature condition of the electrochemical reaction is -20 to 100°C, the pH value is 6 to 10, and the amount of electricity is 2 to 10 times the molar amount of the reactants. In this case, the temperature condition of -20 to 100°C is conducive to the reaction efficiency between the raw material components in the electrochemical reaction system. The pH value of 6 to 10 maintains a weak alkalinity, which is more conducive to converting the chiral phosphoric acid catalyst CPA into CPA - . However, if the pH value is too high, that is, the alkalinity is too strong, the Br2 produced at the anode is easily degraded by the strong base. Therefore, maintaining a weak alkalinity of pH 6 to 10 is more conducive to ensuring the efficiency of converting olefin compounds into chiral bromocyclic compounds. The amount of current Q is related to the current I and the reaction time t, that is, Q = I*t. The amount of current is related to the amount of reactants / substrates in the reaction system. When the amount of current is 2 to 10 times the molar amount of the reactants, it is more conducive to in-situ generation of bromine by electrochemical methods, thereby improving the preparation efficiency of chiral bromocyclic compounds.

[0026] In some embodiments, the heteroatom-containing olefin compound is selected from That is, a tryptamine derivative, the chiral bromocyclic compound obtained at this time is That is, a chiral brominated cyclotryptamine derivative. Wherein, X is selected from a heteroatom selected from N, O, S, and P, and R1 , R 3 R is independently selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, carboxyl, alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, sulfhydryl, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkylester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy and cycloalkylalkyl; 2 Selected from alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, sulfhydryl, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkyl ester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy and cycloalkylalkyl. These chiral bromocyclotryptamine derivatives prepared in the embodiments of the present application are widely used in the synthesis of natural products, such as the synthesis of (–)-chimonanthine dimer alkaloids and (–)-hodgkinsine. The types and synthesis methods of chiral bromocyclotryptamine derivatives are broadened to have better application prospects. The reaction formula in the electrochemical reaction system can be expressed as:

[0027]

[0028] In some specific embodiments, chiral brominated cyclotryptamine derivatives include but are not limited to: wait.

[0029] In other embodiments, the heteroatom-containing olefin compound is selected from That is, an aromatic amide containing an alkenyl group, and the chiral bromocyclic compound obtained at this time is Chiral bromooxazoline. Wherein, X is selected from a heteroatom selected from N, O, S, and P, and R 4 is selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, carboxyl, alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, sulfhydryl, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkyl ester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy and cycloalkylalkyl; R 5One selected from alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, sulfhydryl, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkyl ester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy and cycloalkylalkyl. These chiral bromooxazolines prepared in the embodiments of the present application can be used as chiral ligands or chiral synthetic building blocks. The reaction formula in the electrochemical reaction system can be expressed as:

[0030]

[0031] In some specific embodiments, alkenyl-containing aromatic amides include, but are not limited to: wait.

[0032] In some embodiments, the anode includes at least one of platinum and carbon. Anodes containing these materials can convert Br in the aqueous phase to - Oxidation generates elemental bromine, which can be combined with a water-soluble phase transfer catalyst (PTC) to generate PTC-Br2.

[0033] In some embodiments, the cathode includes at least one of platinum, nickel, and copper. The cathode containing these materials can make the anion Br of PTC-Br2 - It exchanges anions with the chiral phosphoric acid catalyst (CPA) in the organic phase to generate PTC-Br2-CPA that can be dissolved in the organic phase.

[0034] In some embodiments, the phase transfer catalyst (PTC) is a molecule containing exposed nitrogen atoms and ion pairs; it can efficiently capture the elemental bromine generated by anodic oxidation and combine to form PTC-Br2. Using a catalytic amount of phase transfer catalyst (PTC) instead of the traditional equivalent PTC-Br2 reagent can achieve the same catalytic effect, significantly reduce the amount of phase transfer catalyst used, and thus reduce production costs.

[0035] In some embodiments, the phase transfer catalyst is selected from Wherein, Ar7 is independently selected from at least one of aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy, and cycloalkylalkyl. In some specific embodiments, the phase transfer catalyst is selected from At least one of these phase transfer catalysts. These phase transfer catalysts all have a high capture effect on the elemental bromine generated by anodic oxidation, and these phase transfer catalysts combine with elemental bromine to generate PTC-Br2.

[0036] In some embodiments, the chiral phosphoric acid catalyst (CPA) is a phosphoric acid catalyst containing a chiral skeleton; under the action of electric current, the chiral phosphoric acid catalyst CPA is converted into CPA - , which can combine with PTC-Br2 generated by capturing elemental bromine at the anode to generate PTC-Br2-CPA that can be dissolved in the organic phase.

[0037] In some embodiments, the chiral phosphoric acid catalyst is selected from a binaphthyl-based chiral phosphoric acid catalyst Chiral phosphoric acid catalyst based on octahydrobinaphthyl Chiral phosphoric acid catalyst based on spirocyclic skeleton At least one of; wherein Ar1, Ar2, Ar3, Ar4, Ar5, Ar6 are independently selected from at least one of aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy, and cycloalkylalkyl. These specific chiral phosphoric acid catalysts can well catalyze the conversion of chiral phosphoric acid catalyst CPA into CPA under the action of electric current. - , promote CPA - Combined with PTC-Br2, it generates PTC-Br2-CPA which is soluble in organic phase.

[0038] In some specific embodiments, the chiral phosphoric acid catalyst based on binaphthyl includes but is not limited to:

[0039]

[0040] In some specific embodiments, the chiral phosphoric acid catalyst based on octahydrobinaphthyl includes but is not limited to:

[0041]

[0042] In some embodiments, the ionic bromide is selected from at least one of inorganic ionic bromide and organic ionic bromide. In some embodiments, the inorganic ionic bromide is selected from at least one of LiBr, NaBr, KBr, CsBr, MgBr2, and CaBr2. In some embodiments, the organic ionic bromide is selected from n Bu4NBr, n Bu4NBr, n Et4NBr, n At least one of Me4NBr. These ionic bromides used in the embodiments of the present application all have high conductivity, and can efficiently dissociate into bromide ions in the water phase of the electrochemical reaction system. The bromide ions are oxidized into elemental bromine by the anode, which is convenient for the phase transfer catalyst (PTC) to capture and generate PTC-Br2 reagent.

[0043] In some embodiments, the solvent in the alkaline buffer solution includes water and an organic solvent; wherein water provides an aqueous phase for the dissociation of ionic bromide, and the free Br in the aqueous phase - It is oxidized at the anode to generate elemental bromine, which is then combined with a phase transfer catalyst (PTC) dissolved in water to generate PTC-Br2. The organic phase provides a solvent environment for the chiral phosphoric acid catalyst. In the electrochemical reaction system, the anion Br of PTC-Br2 - The negative ions are exchanged with the chiral phosphoric acid catalyst (CPA) in the organic phase to generate PTC-Br2-CPA which can be dissolved in the organic phase. In some embodiments, the volume ratio of water and organic solvent in the alkaline buffer solution is (1-2): (1-2), ensuring that there are sufficient water phase and organic phase in the electrochemical system to provide a sufficient solvent environment for the conversion of heteroatom-containing olefin compounds into chiral bromocyclic compounds.

[0044] In some embodiments, the organic solvent is selected from at least one of toluene, benzene, p-xylene, o-xylene, mesitylene, trifluorotoluene, chlorobenzene, ethyl acetate, dichloromethane, ether, and methyl tert-butyl ether; these organic solvents have good solubility properties for chiral phosphoric acid catalysts, PTC-Br2-CPA, etc.

[0045] In some embodiments, the solute in the alkaline buffer solution is selected from at least one of NaHCO3, Na2CO3, NaH2PO4, and Na2HPO4; after the addition of these solutes, the electrochemical reaction system can be maintained in a weakly alkaline environment with a pH value of 6 to 10, which is conducive to converting the chiral phosphoric acid catalyst CPA into CPA - At the same time, avoid too strong alkalinity, as the Br2 produced at the anode is easily degraded by strong alkali.

[0046] In some embodiments, the electrolyte uses the ionic bromide or an inorganic salt with an oxidation potential lower than the ionic bromide. The electrolyte in the electrochemical reaction system of the embodiment of the present application can directly use ionic bromide. Since ionic bromide also has excellent electrical conductivity and is easily soluble in water, ionic bromide can be directly used as the electrolyte of the electrochemical system, while avoiding the introduction of other ions and reducing the interference of other ions on the electrochemical reaction. The electrolyte can also be additionally added with an inorganic salt with an oxidation potential lower than that of the ionic bromide to ensure that after the ionic bromide is dissociated into bromide ions in the water phase, it can be promptly and efficiently oxidized into elemental bromine at the anode.

[0047] In some embodiments, the inorganic salt is selected from at least one of NaCl, KCl, NaNO3, KNO3, Na2SO4, and K2SO4; these inorganic salts have high solubility in aqueous phase, good conductivity after being dissolved in aqueous phase, and their oxidation potential is lower than that of the ionic bromide, and will not interfere with the oxidation of bromide ions in ionic bromide to elemental bromine at the anode.

[0048] In some embodiments, the reaction mechanism of electrochemical preparation of chiral brominated ring compounds is as shown in the attached Figure 1 As shown, ionic bromide dissociates into bromide ions in the aqueous phase, Br - The anode in the water phase is oxidized to generate elemental bromine, which is then combined with a phase transfer catalyst (PTC) dissolved in water to generate PTC-Br2. - It can react with the chiral phosphoric acid catalyst (CPA) in the organic phase to form anions CPA - The generated PTC-Br2-CPA chiral bromine reagent can convert the heteroatom-containing olefin compound (Formula 1 or Formula 3) into a chiral bromocyclic compound (Formula 2 or Formula 4), and the generated PTC-CPA reacts with Br2 in the aqueous phase. - Negative ion exchange occurs to regenerate PTC soluble in water and CPA soluble in the organic phase, thus entering a new catalytic cycle. At the same time, substances such as NaHCO3 in the alkaline buffer solution are reduced at the cathode.

[0049] The second aspect of the embodiment of the present application provides an electrochemically prepared chiral brominated cyclic compound prepared by the above method, characterized in that the chiral brominated cyclic compound has the general structural formula: X is selected from one heteroatom selected from N, O, S, and P, and R is selected from one heteroatom selected from fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, carboxyl, alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, mercapto, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkylester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy, and cycloalkylalkyl.

[0050] The chiral bromocyclic compound provided in the second aspect of the embodiment of the present application is prepared by the above electrochemical method, which greatly reduces the manufacturing cost of the chiral bromocyclic compound, realizes a green and efficient conversion process, and broadens the types of chiral bromocyclic compounds.

[0051] In some embodiments, the chiral bromocyclic compound comprises That is, chiral brominated cyclotryptamine derivatives; and / or That is, an aromatic amide containing an alkenyl group; wherein X is selected from a heteroatom selected from N, O, S, and P, and R1 , R 3 , R 4 R is independently selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, carboxyl, alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, sulfhydryl, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkylester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy and cycloalkylalkyl; 2 and R 5 Each of the following groups is independently selected from one of alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, thiol, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkyl ester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy and cycloalkylalkyl. Among them, chiral brominated cyclotryptamine derivatives are widely used in the synthesis of natural products, such as the synthesis of (–)-chimonanthine dimer alkaloids and (–)-hodgkinsine. Chiral brominated oxazolines can be used as chiral ligands or chiral synthetic building blocks.

[0052] In some specific embodiments, chiral brominated cyclotryptamine derivatives include but are not limited to: wait.

[0053] In some specific embodiments, alkenyl-containing aromatic amides include, but are not limited to: wait.

[0054] In order to enable the above implementation details and operations of the present application to be clearly understood by those skilled in the art, as well as to demonstrate the significant improvement in the performance of the chiral brominated cyclic compound and the electrochemical method for preparing the chiral brominated cyclic compound in the embodiments of the present application, the above technical scheme is illustrated by multiple embodiments below.

[0055] Example 1

[0056] A chiral bromocyclic compound,

[0057] The electrochemical preparation process includes the following steps:

[0058] Tryptamine derivative 1a (108 mg, 0.3 mmol), (R)-CPA1 catalyst (0.015 mmol, 5 mol%, as shown below), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain the target product 2a with a yield of 96% as a white foamy solid. The schematic diagram of the electrochemical reaction is as follows:

[0059]

[0060] Among them, PTC1 is (R)-CPA catalyst is (R)-CPA1.

[0061] In order to further verify that the purified compound is indeed the target product 2a to be prepared in this example, the obtained product was analyzed by measuring specific rotation, ee value by high performance liquid chromatography, and nuclear magnetic resonance.

[0062] Among them, the analysis of the test is as follows:

[0063] 1. Specific rotation measured at 25°C [α] D 25 :-184.6(c=1.0,CHCl3).

[0064] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 1% i-PrOH hexanes; 1.0 mL / min; retention time: 8.2 min (major), 12.5 min (minor). Calculated result: 95% ee.

[0065] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0066] 1H NMR (400MHz, CDCl3) δ7.76–7.48(m,1H),7.36(d,J=7.6Hz,1H),7.33–7.22(m,1H),7. 15–7.04(m,1H),6.44(s,1H),3.73(dd,J=9.7,7.2Hz,1H),2.90–2.63(m,3H),1.59(s, 9H),1.49(s,9H)ppm.

[0067] 13 C NMR (100MHz, CDCl3) δ153.4,152.2,142.1,132.7,130.3,124.1,123.8,117.4,83.9, 82.1,80.8,62.2,46.2,41.2,28.4,28.3ppm.

[0068] HRMS(CI+)Calcd for C 20 H 27 BrN2NaO4[M+Na] + :461.1046,found:461.1053.

[0069] Example 2

[0070] The effects of different CPA catalysts on chiral bromocyclic compounds were explored. The electrochemical preparation process of formula 2a is the same as that of embodiment 1, except that the following CPA catalysts with different chemical formulas are used respectively.

[0071] The yield of 2a and the ee value were determined by HPLC analysis.

[0072]

[0073] Example 3

[0074] To explore the effects of different types of organic solvents in electrolyte on chiral brominated cyclic compounds. The electrochemical preparation process is the same as that of Example 1, except that different organic solvents are used as shown in Table 1. The yield of 2a and the ee value are determined by high performance liquid chromatography analysis.

[0075] Table 1

[0076]

[0077] From the above test results, it can be seen that when p-xylene and dichloromethane are used as the organic phase in the electrolyte, 2a has a higher yield and ee value.

[0078] Example 4

[0079] A chiral bromocyclic compound

[0080] The electrochemical preparation process includes the following steps:

[0081] Tryptamine derivative 1b (124 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 147 mg of the target product 2b as a white foamy solid, with a calculated yield of 99%. The electrochemical reaction schematic is as follows:

[0082]

[0083] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0084] 1. Specific rotation measured at 25°C [α] D 25 :-142.3(c=1.0,CHCl3).

[0085] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 20% i-PrOH hexanes; 1.0 mL / min; retention time: 13.0 min (minor), 31.9 min (major). The calculated result is 94% ee.

[0086] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0087] 1H NMR (400MHz, CDCl3) δ7.74(d,J=8.1Hz,2H),7.51(d,J=7.1Hz,1H),7.35–7.20(m,4H),7.13–6.99(m,1H),6.41(s,1H),3.73 (dd,J=11.1,7.7Hz,1H),2.93–2.80(m,1H),2.73(dd,J=12.4,4.7Hz,1H),2.64–2.48(m,1H),2.41(s,3H),1.58(s,9H)ppm.

[0088] 13 C NMR (100MHz, CDCl3) δ151.8,143.6,141.5,137.0,131.9,130.5,129.6,127.1,124.3, 123.8,116.9,85.9,83.0,62.1,48.4,42.2,28.2,21.6ppm.

[0089] HRMS(CI+)Calcd for C 22 H 25 BrN2NaO4S[M+Na] + :515.0611,found:515.0617.

[0090] Example 5

[0091] A chiral bromocyclic compound,

[0092] The electrochemical preparation process includes the following steps:

[0093] Tryptamine derivative 1c (118 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 5 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 140 mg of the target product 2c as a white foamy solid, with a calculated yield of 98%. The electrochemical reaction schematic is as follows:

[0094]

[0095] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0096] 1. Specific rotation measured at 25°C [α] D 25 :-183.5(c=1.0,CHCl3).

[0097] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 10% i-PrOH hexanes; 1.0 mL / min; retention time: 8.2 min (major), 11.2 min (minor). Calculated result: 96% ee.

[0098] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0099] 1 H NMR(400MHz, CDCl3)δ7.63(s,1H),7.43–7.26(m,7H),7.14–7.04(m,1H),6.46(s, 1H),5.26–5.11(m,2H),3.78(dd,J=10.8,7.7Hz,1H),2.96–2.67(m,3H),1.54(s,9H)ppm.

[0100] 13 C NMR (100MHz, CDCl3) δ154.0,152.1,142.0,136.5,132.4,130.5,128.5,128.1,128.0, 124.2,123.8,117.5,84.1,82.3,67.3,62.0,46.4,41.3,28.2ppm.

[0101] HRMS(CI+)Calcd for C 23 H 25 BrN2NaO4[M+Na] + :495.0890,found:495.0892.

[0102] Example 6

[0103] A chiral bromocyclic compound,

[0104] The electrochemical preparation process includes the following steps:

[0105] Tryptamine derivative 1d (95.4 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 5 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 122 mg of the target product 2d as a white foamy solid, with a calculated yield of 99%. The electrochemical reaction schematic is as follows:

[0106]

[0107] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0108] 1. Specific rotation measured at 25°C [α] D 25 :-175.6(c=1.0,CHCl3).

[0109] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 10% i-PrOH hexanes; 1.0 mL / min; retention time: 9.2 min (major), 11.9 min (minor). Calculated result: 95% ee.

[0110] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0111] 1 H NMR(400MHz, CDCl3)δ7.66(d,J=8.0Hz,1H),7.38(d,J=7.6Hz,1H),7.35–7.26(m,1H), 7.16–7.08(m,1H),6.40(s,1H),3.85–3.70(m,4H),2.98–2.67(m,3H),1.61(s,9H)ppm.

[0112] 13C NMR (100MHz, CDCl3) δ154.7,152.12,142.0,132.3,130.5,124.2,123.7,117.4,84.0, 82.2,62.1,52.8,46.3,41.1,28.3ppm.

[0113] HRMS(CI+)Calcd for C 17 H 21 BrN2NaO4[M+Na] + :419.0577,found:419.0582.

[0114] Example 7

[0115] A chiral bromocyclic compound,

[0116] The electrochemical preparation process includes the following steps:

[0117] Tryptamine derivative 1e (112 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 121 mg of the target product 2e as a white foamy solid, with a calculated yield of 89%. The electrochemical reaction schematic is as follows:

[0118]

[0119] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0120] 1. Specific rotation measured at 25°C [α] D 25 :-106.6(c=1.0,CHCl3).

[0121] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 1% i-PrOH hexanes; 1.0 mL / min; retention time: 7.4 min (major), 10.3 min (minor). The calculated result is 82% ee.

[0122] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0123] 1 H NMR (400MHz, CDCl3) δ7.58–7.37(m,1H),7.24–7.14(m,1H),6.85(d,J=7.6Hz,1H),6. 48(s,1H),3.74(dd,J=11.1,7.7Hz,1H),3.01(dd,J=12.2,4.6Hz,1H),2.88–2.76(m, 1H),2.70–2.59(m,1H),2.48(s,3H),1.57(s,9H),1.49(s,9H)ppm.

[0124] 13 C NMR (100MHz, CDCl3) δ153.6,152.2,142.7,135.1,130.3,129.1,126.3,114.9,84.5, 82.0,80.7,63.6,46.2,40.2,28.4,28.3,18.5ppm.

[0125] HRMS(CI+)Calcd for C 21 H 29 BrN2NaO4[M+Na] + :475.1203,found:475.1210.

[0126] Example 8

[0127] A chiral bromocyclic compound,

[0128] The electrochemical preparation process includes the following steps:

[0129] The tryptamine derivative 1f (112 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), and NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 134 mg of the target product 2f as a white foamy solid, with a calculated yield of 98%. The electrochemical reaction schematic is as follows:

[0130]

[0131] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0132] 1. Specific rotation measured at 25°C [α] D 25 :-154.0(c=1.0,CHCl3).

[0133] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 1% i-PrOH hexanes; 1.0 mL / min; retention time: 6.1 min (major), 8.7 min (minor). Calculated result: 93% ee.

[0134] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0135] 1 H NMR (400MHz, CDCl3) δ7.45 (s, 1H), 7.16 (s, 1H), 7.09 (d, J = 8.3Hz, 1H), 6.42 (s, 1H), 3.7 2(dd,J=10.7,7.4Hz,1H),2.88–2.63(m,3H),2.32(s,3H),1.58(s,9H),1.49(s,9H)ppm.

[0136] 13C NMR (100MHz, CDCl3) δ153.4,152.2,139.9,133.8,132.7,131.1,124.0,117.3,84.0, 81.9,80.7,62.5,46.1,41.5,28.4,28.3,21.0ppm.

[0137] HRMS(CI+)Calcd for C 21 H 29 BrN2NaO4[M+Na] + :475.1203,found:475.1209.

[0138] Example 9

[0139] A chiral bromocyclic compound,

[0140] The electrochemical preparation process includes the following steps:

[0141] 1g (140mg, 0.3mmol) of tryptamine derivative, (R)-CPA1 (12.5mg, 0.015mmol, 5mol%), PTC1 (11.3mg, 0.03mmol, 10mol%), NaHCO3 (42mg, 0.5mmol), and NaBr (515mg, 5.0mmol) were weighed into a non-separated electrolytic cell, toluene (6mL) and H2O (5mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 2g of the target product as a white foamy solid of 155mg, with a calculated yield of 95%. The schematic diagram of the electrochemical reaction is as follows:

[0142]

[0143] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0144] 1. Specific rotation measured at 25°C [α] D 25 :-106.6(c=1.0,CHCl3).

[0145] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 4% i-PrOH hexanes; 1.0 mL / min; retention time: 8.2 min (major), 11.5 min (minor). The calculated result is 93% ee.

[0146] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0147] 1 H NMR (400MHz, CDCl3) δ7.65–7.28(m,6H),7.03–6.83(m,2H),6.41(s,1H),5.03(s, 2H),3.71(dd,J=10.5,6.6Hz,1H),2.88–2.78(m,1H),2.78–2.60(m,2H),1.57(s,9H),1.49(s,9H)ppm.

[0148] 13 C NMR (100MHz, CDCl3) δ155.8,153.4,152.3,136.7,136.0,133.8,128.6,128.1,127.6, 118.4,117.1,109.9,84.1,81.9,80.8,70.7,62.3,46.1,41.2,28.4,28.3ppm.

[0149] HRMS(CI+)Calcd for C 27 H 33 BrN2NaO5[M+Na] + :567.1465,found:567.1472.

[0150] Example 10

[0151] A chiral bromocyclic compound,

[0152] The electrochemical preparation process includes the following steps:

[0153] The tryptamine derivative 1h (114 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), and NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 133 mg of the target product 2h as a white foamy solid, with a calculated yield of 95%. The electrochemical reaction schematic is as follows:

[0154]

[0155] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0156] 1. Specific rotation measured at 25°C [α] D 25 :-185.2(c=1.0,CHCl3).

[0157] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 4% i-PrOH hexanes; 1.0 mL / min; retention time: 8.2 min (major), 11.5 min (minor). The calculated result is 93% ee.

[0158] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0159] 1 H NMR (400MHz, CDCl3) δ7.56 (s, 1H), 7.06 (dd, J = 7.7, 2.6Hz, 1H), 7.03–6.94 (m, 1H), 6. 44(s,1H),3.84–3.69(m,1H),2.92–2.79(m,1H),2.79–2.63(m,2H),1.58(s,9H),1.49 (s,9H)ppm.

[0160] 13 C NMR (100MHz,CDCl3)δ159.4(d, 1J C-F =243.3Hz),153.3,152.07,138.2,134.3,118.6,117.2(d, 2 J C-F =23.3Hz),110.6(d, 2 J C-F =24.4Hz),84.3,82.3,80.9,61.4,46.1,41.4,28.4, 28.3ppm.

[0161] 19 F NMR (376MHz, CDCl3) δ-118.3ppm.

[0162] HRMS(CI+)Calcd for C 20 H 26 BrFN2NaO4[M+Na] + :479.0952,found:479.0958.

[0163] Embodiment 11

[0164] A chiral bromocyclic compound,

[0165] The electrochemical preparation process includes the following steps:

[0166] The tryptamine derivative 1i (132 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), and NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 145 mg of the target product 2i as a white foamy solid, with a calculated yield of 93%. The electrochemical reaction schematic is as follows:

[0167]

[0168] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0169] 1. Specific rotation measured at 25°C [α] D 25 :-125.5(c=1.0,CHCl3).

[0170] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 2% i-PrOH hexanes; 1.0 mL / min; retention time: 5.7 min (major), 7.9 min (minor). Calculated result: 94% ee.

[0171] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0172] 1 H NMR (400MHz, CDCl3) δ7.66–7.44(m,2H),7.39(d,J=8.7Hz,1H),6.44(s,1H),3 .77(dd,J=11.0,6.9Hz,1H),2.92–2.63(m,3H),1.59(s,9H),1.49(s,9H)ppm.

[0173] 13 C NMR (100MHz, CDCl3) δ153.3,151.8,141.2,134.7,133.3,126.9,118.7,116.2,84.2, 82.5,80.9,61.1,46.2,41.8,28.4,28.3ppm.

[0174] HRMS(CI+)Calcd for C 20 H 26 Br2N2NaO4[M+Na] + :539.0152,found:539.0155.

[0175] Example 12

[0176] A chiral bromocyclic compound,

[0177] The electrochemical preparation process includes the following steps:

[0178] Tryptamine derivative 1j (112 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 125 mg of the target product 2j as a white foamy solid, with a calculated yield of 92%. The electrochemical reaction schematic is as follows:

[0179]

[0180] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0181] 1. Specific rotation measured at 25°C [α] D 25 :-190.9(c=1.0,CHCl3).

[0182] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 1% i-PrOH hexanes; 1.0 mL / min; retention time: 7.1 min (major), 10.4 min (minor). The calculated result is 94% ee.

[0183] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0184] 1 H NMR (400MHz, CDCl3) δ7.48 (s, 1H), 7.25 (d, J = 7.8Hz, 1H), 6.93 (d, J = 7.8Hz, 1H), 6.44(s,1H),3.73(dd,J=10.3,7.5Hz,1H),2.89–2.65(m,3H),2.36(s,3H),1.60(s,9H),1.50 (s,9H)ppm.

[0185] 13C NMR (100MHz, CDCl3) δ153.4,152.3,142.3,140.8,129.9,125.0,123.4,117.9,84.2, 82.0,80.7,62.6,46.3,42.0,28.4,28.3,21.9ppm.

[0186] HRMS(CI+)Calcd for C 21 H 29 BrN2NaO4[M+Na] + :475.1203,found:475.1207.

[0187] Embodiment 13

[0188] A chiral bromocyclic compound,

[0189] The electrochemical preparation process includes the following steps:

[0190] The tryptamine derivative 1k (112 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), and NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 132 mg of the target product 2k as a white foamy solid, with a calculated yield of 97%. The electrochemical reaction schematic is as follows:

[0191]

[0192] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0193] 1. Specific rotation measured at 25°C [α] D 25 :-125.7(c=1.0,CHCl3).

[0194] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 2% i-PrOH hexanes; 1.0 mL / min; retention time: 11.6 min (major), 12.9 min (minor). The calculated result is 92% ee.

[0195] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0196] 1 H NMR (400MHz, CDCl3) δ7.24–7.17(m,1H),7.17–7.07(m,2H),6.24(s,1H),3.5 9–3.47(m,1H),2.87–2.62(m,3H),2.30(s,3H),1.53(s,9H),1.50(s,9H)ppm.

[0197] 13 C NMR (100MHz, CDCl3) δ153.7,153.6,141.6,135.1,132.4,131.0,126.2,120.3,86.0, 82.0,80.6,62.2,45.6,37.9,28.6,28.2,19.3ppm.

[0198] HRMS(CI+)Calcd for C 21 H 29 BrN2NaO4[M+Na] + :475.1203,found:475.1208.

[0199] Embodiment 14

[0200] A chiral bromocyclic compound,

[0201] The electrochemical preparation process includes the following steps:

[0202] Tryptamine derivative 1l (123 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 143 mg of the target product 2l as a white foamy solid, with a calculated yield of 98%. The electrochemical reaction schematic is as follows:

[0203]

[0204] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0205] 1. Specific rotation measured at 25°C [α] D 25 :-138.7(c=1.0,CHCl3).

[0206] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 5% i-PrOH hexanes; 1.0 mL / min; retention time: 8.3 min (major), 9.5 min (minor). The calculated result is 76% ee.

[0207] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0208] 1 H NMR(400MHz, CDCl3)δ7.77(s,1H),7.42–7.20(m,7H),7.17–6.96(m,1H),5.13(s, 2H),3.51(t,J=9.5Hz,1H),3.03–2.93(m,1H),2.87(dd,J=12.7,6.5Hz,1H),2.74–2.60(m,1H),2.16(s,3H),1.56(s,9H)ppm.

[0209] 13C NMR (100MHz, CDCl3) δ153.1,152.0,142.2,136.7,131.7,130.3,128.5,127.9,127.7, 123.7,123.1,118.3,88.4,82.0,70.2,66.7,45.8,36.0,28.4,24.4ppm.

[0210] HRMS(CI+)Calcd for C 24 H 27 BrN2NaO4[M+Na] + :509.1046,found:509.1050.

[0211] Embodiment 15

[0212] A chiral bromocyclic compound,

[0213] The electrochemical preparation process includes the following steps:

[0214] The tryptophan derivative 1m (88.5 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), and NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 104 mg of the target product 2m as a white foamy solid, with a calculated yield of 93%. The electrochemical reaction schematic is as follows:

[0215]

[0216] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0217] 1. Specific rotation measured at 25°C [α] D 25 :-107.3(c=1.0,CHCl3).

[0218] 2. EE value determination by high performance liquid chromatography: chiral column Daicel IC column; 3% i-PrOH hexanes; 1.0 mL / min; retention time: 13.5 min (minor), 14.5 min (major). The calculated result is 90% ee.

[0219] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0220] 1 H NMR(400MHz, CDCl3)δ7.88(s,1H),7.55–7.18(m,7H),7.17–6.97(m,1H),6.29(s, 1H),5.49–5.19(m,2H),4.00(t,J=8.1Hz,1H),3.49(ddd,J=11.2,9.1,4.8Hz,1H),2.95–2.83(m,1H),2.83–2.74(m,1H)ppm.

[0221] 13 C NMR (100MHz, CDCl3) δ152.4,141.5,135.9,131.7,130.6,128.7,128.4,128.0,124.9, 124.2,115.0,100.7,68.0,67.6,61.8,45.0ppm.

[0222] HRMS(CI+)Calcd for C 18 H 16 BrNNaO3[M+Na] + :396.0206,found:396.0210.

[0223] Example 16

[0224] A chiral bromocyclic compound,

[0225] The electrochemical preparation process includes the following steps:

[0226] The tryptophan derivative 1n (112 mg, 0.3 mmol), (R)-CPA1 (12.5 mg, 0.015 mmol, 5 mol%), PTC1 (11.3 mg, 0.03 mmol, 10 mol%), NaHCO3 (42 mg, 0.5 mmol), and NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 121 mg of the target product 2n as a white foamy solid, with a calculated yield of 89%. The electrochemical reaction schematic is as follows:

[0227]

[0228] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0229] 1. Specific rotation measured at 25°C [α] D 25 :-34.0(c=1.0,CHCl3).

[0230] 2. EE value determination by high performance liquid chromatography: chiral column OD column; 5% i-PrOH hexanes; 1.0 mL / min; retention time: 8.8 min (major), 9.6 min (minor). The calculated result is 92% ee.

[0231] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0232] 1 H NMR (400MHz, CDCl3) δ7.90–7.64(m,1H),7.52(d,J=1.1Hz,1H),7.50–7.26(m,6H),6. 26(s,1H),5.32(q,J=12.3Hz,2H),4.01(t,J=8.1Hz,1H),3.50(ddd,J=11.0,9.4,4.7 Hz,1H),2.93–2.81(m,1H),2.81–2.71(m,1H)ppm.

[0233] 13C NMR (100MHz, CDCl3) δ152.2,140.6,135.6,133.8,133.5,128.7,128.4,128.0,127.9, 116.5,116.4,100.9,68.0,67.8,60.5,44.9ppm.

[0234] HRMS(CI+)Calcd for C 18 H 15 Br2NNaO3[M+Na] + :473.9311,found:473.9315.

[0235] Embodiment 17

[0236] A chiral bromocyclic compound,

[0237] The electrochemical preparation process includes the following steps:

[0238] 3a (71.2 mg, 0.3 mmol), (R)-CPA2 (11.4 mg, 0.015 mmol, 5 mol%), PTC2 (21.1 mg, 0.06 mmol, 20 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 94.7 mg of the target product 4a as a white solid, with a calculated yield of 99%. The electrochemical reaction schematic is as follows:

[0239]

[0240] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0241] 1. Specific rotation measured at 25°C [α] D 25 :+15.4(c=1.0,CHCl3).

[0242] 2. EE value determination by high performance liquid chromatography: chiral column OD column; 1% i-PrOH hexanes; 1.0 mL / min; retention time: 6.2 min (minor), 7.7 min (major). The calculated result is 92% ee.

[0243] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0244] 1 H NMR (400MHz, CDCl3) δ8.26–8.17(m,2H),7.54–7.41(m,3H),7.39–7.31(m,2H),7.25– 7.18(m,1H),7.18–7.11(m,1H),3.76(d,J=11.2Hz,1H),3.53(d,J=11.2Hz,1H),1.91 (s,3H).

[0245] 13 C NMR (100MHz, CDCl3) δ156.2,139.1,132.3,131.6,129.6,128.33,128.32,127.1, 126.8,125.6,123.3,78.1,39.8,24.9ppm.

[0246] HRMS(CI+)Calcd for C 16 H 15 BrNO[M+H] + :316.0332,found:316.0328.

[0247] Embodiment 18

[0248] A chiral bromocyclic compound,

[0249] The electrochemical preparation process includes the following steps:

[0250] 3b (79.6 mg, 0.3 mmol), (R)-CPA2 (11.4 mg, 0.015 mmol, 5 mol%), PTC2 (21.1 mg, 0.06 mmol, 20 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 6 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 103 mg of the target product 4b as a white solid, with a calculated yield of 99%. The electrochemical reaction schematic is as follows:

[0251]

[0252] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0253] 1. Specific rotation measured at 25°C [α] D 25 :-4.3(c=1.0,CHCl3).

[0254] 2. EE value determination by high performance liquid chromatography: chiral column OD column; 1% i-PrOH hexanes; 1.0 mL / min; retention time: 6.2 min (minor), 6.9 min (major). The calculated result is 95% ee.

[0255] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0256] 1 H NMR (400MHz, CDCl3) δ8.22–8.12(m,2H),7.54–7.41(m,3H),7.36–7.28(m,2H),7.24– 7.17(m,1H),7.13–7.06(m,1H),3.95(d,J=10.9Hz,1H),3.79(d,J=10.9Hz,1H),2.47 (hept,J=6.8Hz,1H),1.15(d,J=6.8Hz,3H),0.96(d,J=6.9Hz,3H)ppm.

[0257] 13C NMR (100MHz, CDCl3) δ155.8,139.7,132.5,131.4,129.1,128.3,127.8,126.5,125.7, 125.0,123.8,84.2,39.6,37.1,18.0,16.0ppm.

[0258] HRMS(CI+)Calcd for C 18 H 19 BrNO[M+H] + :344.0645,found:344.0654.

[0259] Embodiment 19

[0260] A chiral bromocyclic compound,

[0261] The electrochemical preparation process includes the following steps:

[0262] 3c (73 mg, 0.3 mmol), (R)-CPA2 (11.4 mg, 0.015 mmol, 5 mol%), PTC2 (21.1 mg, 0.06 mmol, 20 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 5 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 96 mg of the target product 4c as a white solid, with a calculated yield of 99%. The electrochemical reaction schematic is as follows:

[0263]

[0264] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0265] 1. Specific rotation measured at 25°C [α] D 25 :+33.7(c=1.0,CHCl3).

[0266] 2. EE value determination by high performance liquid chromatography: chiral column OD column; 1% i-PrOH hexanes; 1.0 mL / min; retention time: 8.3 min (minor), 13.2 min (major). The calculated result is 95% ee.

[0267] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0268] 1 H NMR(400MHz, CDCl3)δ7.82(s,1H),7.56–7.42(m,1H),7.40–7.26(m,2H),7.26 –7.01(m,3H),3.75(d,J=11.2Hz,1H),3.52(d,J=11.2Hz,1H),1.90(s,3H)ppm.

[0269] 13 C NMR (100MHz, CDCl3) δ152.8,139.0,136.6,130.7,130.69,129.67,127.8,127.0, 126.7,125.3,123.4,78.5,39.6,24.8ppm.

[0270] HRMS(CI+)Calcd for C 14 H 13 BrNOS[M+H] + :321.9896,found:321.9898.

[0271] Embodiment 20

[0272] A chiral bromocyclic compound,

[0273] The electrochemical preparation process includes the following steps:

[0274] 3d (89.8 mg, 0.3 mmol), (R)-CPA2 (11.4 mg, 0.015 mmol, 5 mol%), PTC2 (21.1 mg, 0.06 mmol, 20 mol%), NaHCO3 (42 mg, 0.5 mmol), NaBr (515 mg, 5.0 mmol) were weighed into a non-separated electrolytic cell, toluene (6 mL) and H2O (5 mL) were added, and the mixture was stirred rapidly (1000 r / min) on a stirrer, and a current of 4 mA was passed. The mixture was reacted at room temperature for 5 hours, and the electrodes were removed. The reaction solution was extracted three times with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was used for silica gel column chromatography to obtain 105 mg of the target product 4d as a white solid, with a calculated yield of 99%. The electrochemical reaction schematic is as follows:

[0275]

[0276] After the preparation in this step is completed, in order to further verify that the purified compound is indeed the target product to be prepared in this example, the obtained product is analyzed by measuring specific rotation, high performance liquid chromatography to measure ee value, and nuclear magnetic resonance. Among them, the test analysis is as follows:

[0277] 1. Specific rotation measured at 25°C [α] D 25 :-16.6(c=1.0,CHCl3).

[0278] 2. EE value determination by high performance liquid chromatography: chiral column OD column; 1% i-PrOH hexanes; 1.0 mL / min; retention time: 5.1 min (minor), 5.8 min (major). The calculated result is 94% ee.

[0279] 3. Hydrogen spectrum, carbon spectrum and high-resolution mass spectrometry of nuclear magnetic resonance analysis.

[0280] 1 H NMR (400MHz, CDCl3) δ8.28–8.14(m,2H),7.54–7.40(m,3H),7.39–7.24(m,3H),7.24–7.14(m,1H),4.51(s,1H),2.83–2. 70(m,1H),2.51–2.37(m,1H),2.19–2.01(m,2H),2.01–1.87(m,2H),1.82(d,J=13.3Hz,1H),1.69(d,J=13.4Hz,1H)ppm.

[0281] 13 C NMR (100MHz, CDCl3) δ155.5,138.8,132.5,131.7,129.2,128.5,127.9,127.8,126.4, 126.0,124.8,79.2,53.6,30.0,29.6,20.7,19.6ppm.

[0282] HRMS(CI+)Calcd for C 19 H 19 BrNO[M+H] + :356.0645,found:356.0647.

[0283] It can be seen from the above examples that the chiral brominated cyclic compounds of different molecular configurations prepared by electrochemical methods in Examples 1 to 20 of the present application all have relatively high yields.

[0284] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims

1. A method for electrochemically preparing a chiral brominated cyclic compound, characterized in that: The following steps are involved: In a non-separated electrolytic cell comprising a cathode and an anode, an olefin compound containing a heteroatom, a chiral phosphoric acid catalyst, a phase transfer catalyst, an ionic bromide and an electrolyte are added, and an electrochemical reaction is carried out in an alkaline buffer solution to obtain a chiral bromocyclic compound; Wherein, the structural formula of the heteroatom-containing olefin compound is The chiral bromocyclic compound obtained is Alternatively, the general structural formula of the heteroatom-containing olefin compound is The chiral bromocyclic compound is obtained as Wherein, X is selected from a heteroatom selected from N, O, S, and P, and R 1 , R 3 , R 4 R is independently selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, hydroxyl, amino, carboxyl, alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, sulfhydryl, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkylester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy and cycloalkylalkyl; 2 and R 5 Each of the following is independently selected from one of alkyl, haloalkyl, alkoxy, alkylthio, alkenyl, alkynyl, nitro, mercapto, hydroxyalkyl, hydroxyalkoxy, aminoalkoxy, alkyl ester, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl, aryloxy, heteroaryloxy, haloalkyloxy and cycloalkylalkyl; The chiral phosphoric acid catalyst is selected from at least one of a chiral phosphoric acid catalyst based on binaphthyl and a chiral phosphoric acid catalyst based on octahydrobinaphthyl; wherein the chiral phosphoric acid catalyst based on binaphthyl is selected from: The chiral phosphoric acid catalyst based on octahydrobinaphthyl is selected from: The phase transfer catalyst is selected from At least one of; The molar concentration of the chiral phosphoric acid catalyst is 0.01 to 50 mol / L, the molar concentration of the phase transfer catalyst is 0.01 to 50 mol / L, the concentration of the heteroatom-containing olefin compound is 0.01 to 1.0 mol / L, the concentration of the ionic bromide is 0.02 to 5.0 mol / L, and the concentration of the electrolyte is 0.02 to 5.0 mol / L.

2. The method for electrochemically preparing a chiral brominated cyclic compound according to claim 1, characterized in that: The temperature conditions of the electrochemical reaction are -20 to 100° C., the pH value is 6 to 10, and the amount of electricity passed is 2 to 10 times the molar amount of the reactants.

3. The method for electrochemically preparing a chiral brominated cyclic compound according to any one of claims 1 to 2, characterized in that: The ionic bromide is selected from at least one of inorganic ionic bromide and organic ionic bromide; And / or, the solvent in the alkaline buffer solution includes water and an organic solvent; And / or, the electrolyte is the ionic bromide or an inorganic salt having an oxidation potential lower than that of the ionic bromide; And / or, the anode includes at least one of platinum and carbon; And / or, the cathode includes at least one of platinum, nickel, and copper.

4. The method for electrochemically preparing a chiral brominated cyclic compound according to claim 3, characterized in that: The inorganic salt is selected from at least one of NaCl, KCl, NaNO3, KNO3, Na2SO4, and K2SO4; And / or, the solute in the alkaline buffer solution is selected from at least one of NaHCO3, Na2CO3, NaH2PO4, and Na2HPO4; and / or, the organic solvent is selected from at least one of toluene, benzene, p-xylene, o-xylene, mesitylene, trifluorotoluene, chlorobenzene, ethyl acetate, dichloromethane, ether and methyl tert-butyl ether; And / or, the inorganic ion bromide is selected from at least one of LiBr, NaBr, KBr, CsBr, MgBr2, and CaBr2; And / or, the organic ion bromide is selected from n Bu4NBr, n Bu4NBr, n Et4NBr, n At least one of Me4NBr.

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