N-substituted benzene ring biological isostere and preparation method thereof

Abstract

The invention provides an N-substituted benzene ring bioisostere and a preparation method thereof, and the N-substituted benzene ring bioisostere is generated by reacting a benzene-containing compound with alkyl carboxylic acid under photocatalysis and electrochemical conditions in the presence of an organic solvent, alkali, electrolyte and a catalyst. The synthesis method provided by the invention is simple to operate and high in atom economy, and the obtained target compound has the characteristics of good functional group compatibility and wide substrate. And the N-substituted benzene ring bioisostere prepared on the basis of the method can be applied to development and modification of pilot drugs, and has good application potential in pharmaceutical chemistry.

Description

Technical Field

[0001] The present invention belongs to the technical field of synthesis of medicines and pharmaceutical intermediates, and specifically relates to an N-substituted benzene ring bioisostere and a preparation method thereof, and in particular relates to an N-substituted bicyclo[1.1.1]pentane, an N-substituted bicyclo[2.1.1]pentane, an N-substituted bicyclo[2.2.1]heptane, an N-substituted bicyclo[2.2.2]octane or an N-substituted bicyclo[2.2.1]heptane and a preparation method thereof. Background Art

[0002] The discovery of bioisosteres has been stimulated by the improvement of the physicochemical properties and pharmacokinetic characteristics of candidate drugs. The benzene ring is the basic unit in drug molecules. 3 After the bioisostere of the structure replaces the benzene ring, it exhibits stronger physical and chemical properties, such as water solubility, oral absorption characteristics, and metabolic stability.

[0003] Traditional methods have made some progress in the synthesis of N-substituted bicyclo[1.1.1]pentanes. For example, the June 2018 issue of the journal Nature, page 83, published “Decarboxylative sp3 C–N coupling via dual copper and photoredox catalysis”. The synthetic route used is mainly: The mechanism is to activate alkyl carboxylic acid by iodo-trimethylbenzene diacetate, then generate alkyl free radicals by single electron transfer decarboxylation under photocatalytic conditions, and then realize sp3 C–N coupling by copper capture of free radicals and reduction elimination. For example, the April 2020 issue of the journal "Nature" on page 220 disclosed "Copper-mediated synthesis of drug-like bicyclopentanes", and the synthetic route used is mainly:

[0004] The mechanism is to activate alkyl carboxylic acid by iodo-trimethylbenzene diacetate, then generate alkyl radicals by single electron transfer decarboxylation under photocatalytic conditions, add alkyl radicals to [1,1,1] propellerane radicals, and then achieve sp3 C–N coupling by copper trapping free radicals and reductive elimination.

[0005] However, the functional group compatibility and operability of multi-step synthesis of reported methods have severely limited the development of N-substituted bicyclic benzene bioisosteres, and there are few reports on the synthesis of other N-substituted bicyclic benzene bioisosteres. Therefore, the development of new synthesis methods for N-substituted bicyclic benzene bioisosteres is of great significance, which will greatly promote the development of candidate drug modification. Summary of the invention

[0006] In view of the deficiencies in the prior art, the present invention provides an N-substituted benzene ring bioisostere and a preparation method thereof.

[0007] The objective of the present invention is achieved through the following technical solutions:

[0008] In a first aspect, the present invention provides an N-substituted benzene ring bioisostere, including any one of N-substituted bicyclo[1.1.1]pentane, N-substituted bicyclo[2.1.1]pentane, N-substituted bicyclo[2.2.1]heptane, and N-substituted bicyclo[2.2.2]octane;

[0009] The structure of the N-substituted bicyclo[1.1.1]pentane is shown in Formula I, Formula II or Formula III; the structure of the N-substituted bicyclo[2.1.1]pentane is shown in Formula IV; the structure of the N-substituted bicyclo[2.2.2]octane is shown in Formula V; the structure of the N-substituted bicyclo[2.2.1]heptane is shown in Formula VI;

[0010]

[0011] Among them, R 1 is hydrogen, methyl, N-BOC-L-alanine, ethyl acetate, pinacol borate, hydroxymethyl, α,α-dimethylacetonitrile, acetonitrile, halogen, difluoromethoxy, trifluoromethoxy, trifluoromethylthio, trifluoromethyl, methyl formate, 4-cyano, 4-methylsulfonyl, benzyl (S)-(2-((tert-butyloxycarbonyl)amino)propionyl)glycine, 3-ethylpiperidine-2,6-dione, (5R,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl any one of: acetate, (1R,2S)-2-(2,2-dichloroacetylamino)-3-fluoro-1-(4-(methylsulfonyl)phenyl)propyl acetate, ((3aR,4R,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl acetate, and (8R,9S,13S,14S,17S)-17-acetoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-benzoate;

[0012] R 2 Any one of hydrogen, methyl, NHBoc, and halogen;

[0013] R 3 Any one of hydrogen, dimethylphosphine, and phenoxy;

[0014] R 4 Any of hydrogen and halogen;

[0015] R 5 is any one of hydrogen, halogen, and methoxy;

[0016] R 6 is any of carbon or nitrogen atoms;

[0017] R 7 Any of carbon or nitrogen atoms

[0018] R 8 is either hydrogen or methyl formate;

[0019] R 9 Any one of difluoromethyl, phenyl, (tert-butyldimethylsilyloxy)methyl, cyano, formanilide, 4-phenylpiperazine-1-carbonyl, tert-butylaminoformyl, tert-butoxycarbonyl, (((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)carbonyl, and 3,7-dimethyl-6-octenyloxycarbonyl;

[0020] R 10 It is any of hydrogen and halogen.

[0021] In a second aspect, the present invention provides a method for preparing an N-substituted benzene ring bioisostere, comprising the following steps:

[0022] In the presence of an organic solvent, a base, an electrolyte and a catalyst, a benzene-containing compound reacts with an alkyl carboxylic acid under photocatalytic and electrochemical conditions to generate an N-substituted benzene ring bioisostere.

[0023] Preferably, the specific steps of the preparation method are:

[0024] In a reaction container, a benzene compound, an organic solvent, a catalyst, an alkali, an electrolyte, and a part of alkyl carboxylic acids are added, a carbon cloth electrode is used as an anode, and a glassy carbon or nickel foam electrode is used as a cathode, and the mixture is stirred at 20 to 25° C. for 8 to 12 hours under 1 to 3 mA current and irradiation with ultraviolet light; then the remaining alkyl carboxylic acids are added and stirring is continued for 3 to 6 hours to obtain an N-substituted benzene ring bioisostere.

[0025] Preferably, the benzene-containing compound is selected from p-methylaniline, aniline, N-BOC-L-4-aminophenylalanine ethyl ester, ethyl p-aminophenylacetate, 4-aminophenylboronic acid pinacol ester, p-aminobenzyl alcohol, 2-aminodiphenyl ether, 2-naphthylamine, 2-(4-aminophenyl)-2-methylpropionitrile, 4-chloroaniline, 4-bromoaniline, 4-fluoroaniline, 3,5-dichloroaniline, 4-trifluoromethoxyaniline, 4-(trifluoromethylthio)aniline, N-BOC-m-phenylenediamine, 4-trifluoromethylaniline, 4-aminobenzoic acid methyl ester, 4-cyanoaniline, 4-methylsulfonylaniline, p-aminophenylacetonitrile, 4-(difluoromethoxy)aniline, (S)-indoline-2-carboxylic acid methyl ester, m-methyl Aniline, 2-(dimethylphosphino)aniline, 5-amino-2-methylpyridine, 6-bromo-3-aminopyridine, 2-fluoro-5-aminopyridine, 2-chloro-5-aminopyridine, 3-amino-5-chloropyridine, 6-methyl-3-amino-2-chloropyridine, 2-methoxy-3-aminopyridine, 5-amino-2-methylpyrimidine, aminoglutethimide, benzyl (S)-(3-(4-aminophenyl)-2-((tert-butyloxycarbonyl)amino)propionyl)glycine, ((3aR,4R,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetracycline trahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-(4-aminophenyl)acetate, (5R,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofur o[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl At least one of (1R,2S)-2-(2,2-dichloroacetylamino)-3-fluoro-1-(4-(methylsulfonyl)phenyl)propyl 2-(4-aminophenyl)acetate, (8R,9S,13S,14S,17S)-17-(2-(4-aminophenyl)acetoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-3-benzoate, indoline and p-methylaniline.

[0026] Preferably, the alkyl carboxylic acid is selected from at least one of 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid, 3-(difluoromethyl)bicyclo[1.1.1]pentane-1-carboxylic acid, 3-(carboxanilide)bicyclo[1.1.1]pentane-1-carboxylic acid, 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid, 4-(methoxycarbonyl)bicyclo[2.2.1]heptane-1-carboxylic acid and 4-(phenyl)bicyclo[2.1.1]hexane-1-carboxylic acid.

[0027] Preferably, the molar ratio of the benzene-containing compound to the alkyl carboxylic acid is 1:1.5 to 3.5, more preferably 1:2 to 3, most preferably 1:3.

[0028] Preferably, the organic solvent is selected from N,N-dimethylformamide.

[0029] Preferably, the base is selected from triethylamine.

[0030] Preferably, the electrolyte is selected from tetrabutylammonium fluoroborate.

[0031] Preferably, the catalyst includes catalyst 1 and catalyst 2;

[0032] The catalyst 1 is ferrous acetate; the catalyst 2 is selected from at least one of copper acetylacetonate, Cu(hfacac)2, 4a, and 4b compounds;

[0033] The structural formulas of the compounds 4a and 4b are as follows:

[0034]

[0035] More preferably, the catalyst 2 is copper acetylacetonate.

[0036] Preferably, the molar ratio of the catalyst to the benzene-containing compound is 0.2 to 0.4:1;

[0037] The molar ratio of triethylamine to the benzene-containing compound is 0.4 to 0.6:1;

[0038] The molar ratio of the tetrabutylammonium fluoroborate to the benzene-containing compound is 1 to 1.4:1.

[0039] Preferably, the power of the purple light is 4-8W and the wavelength is 390nm.

[0040] Compared with the prior art, the present invention has the following beneficial effects:

[0041] (1) The synthetic method provided by the present invention is simple to operate and has high atom economy. The target compound obtained has the characteristics of good functional group compatibility and a wide range of substrates.

[0042] (2) The synthetic method provided by the present invention uses commercially available raw materials, and the product N-substituted benzene ring bioisostere can be used in the development and modification of lead drugs, and has good application potential in medicinal chemistry. DETAILED DESCRIPTION

[0043] The present invention is described in detail below in conjunction with specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, several variations and improvements may be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

[0044] In a specific embodiment of the present invention, a method for preparing an N-substituted benzene ring bioisostere is provided, wherein a benzene-containing compound is reacted with an alkyl carboxylic acid under photocatalytic and electrochemical conditions in the presence of an organic solvent, a base, an electrolyte and a catalyst to generate an N-substituted benzene ring bioisostere.

[0045] The specific preparation steps are:

[0046] In a reaction container, a benzene compound, an organic solvent, a catalyst, an alkali, an electrolyte, and a part of an alkyl carboxylic acid are added, a carbon cloth electrode is used as an anode, and a glassy carbon or nickel foam electrode is used as a cathode. Under the irradiation of a current of 1 to 3 mA and a 4 to 8 W ultraviolet light with a wavelength of 390 nm, stirring is performed at a temperature of 20 to 25° C. for 8 to 12 hours; then, the remaining alkyl carboxylic acid is added and stirring is continued for 3 to 6 hours to obtain an N-substituted benzene ring bioisostere.

[0047] In a specific embodiment, the benzene-containing compound is selected from p-methylaniline, aniline, N-BOC-L-4-aminophenylalanine ethyl ester, ethyl p-aminophenylacetate, 4-aminophenylboronic acid pinacol ester, p-aminobenzyl alcohol, 2-aminodiphenyl ether, 2-naphthylamine, 2-(4-aminophenyl)-2-methylpropionitrile, 4-chloroaniline, 4-bromoaniline, 4-fluoroaniline, 3,5-dichloroaniline, 4-trifluoromethoxyaniline, 4-(trifluoromethylthio)aniline, N-BOC-m-phenylenediamine, 4-trifluoromethylaniline, 4-aminobenzoic acid methyl ester, 4-cyanoaniline, 4-methylsulfonylaniline, p-aminophenylacetonitrile, 4-(difluoromethoxy)aniline, (S)-indoline-2-carboxylic acid methyl ester, m-Methylaniline, 2-(dimethylphosphino)aniline, 5-amino-2-methylpyridine, 6-bromo-3-aminopyridine, 2-fluoro-5-aminopyridine, 2-chloro-5-aminopyridine, 3-amino-5-chloropyridine, 6-methyl-3-amino-2-chloropyridine, 2-methoxy-3-aminopyridine, 5-amino-2-methylpyrimidine, aminoglutethimide, benzyl (S)-(3-(4-aminophenyl)-2-((tert-butyloxycarbonyl)amino)propionyl)glycine, ((3aR,4R,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetracycline trahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-(4-aminophenyl)acetate, (5R,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofur o[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl At least one of (1R,2S)-2-(2,2-dichloroacetylamino)-3-fluoro-1-(4-(methylsulfonyl)phenyl)propyl 2-(4-aminophenyl)acetate, (8R,9S,13S,14S,17S)-17-(2-(4-aminophenyl)acetoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-3-benzoate, indoline and p-methylaniline.

[0048] In a specific embodiment, the alkyl carboxylic acid is selected from at least one of 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid, 3-(difluoromethyl)bicyclo[1.1.1]pentane-1-carboxylic acid, 3-(formanilide)bicyclo[1.1.1]pentane-1-carboxylic acid, 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid, 4-(methoxycarbonyl)bicyclo[2.2.1]heptane-1-carboxylic acid, and 4-(phenyl)bicyclo[2.1.1]hexane-1-carboxylic acid.

[0049] In one specific embodiment, the molar ratio of the benzene-containing compound to the alkyl carboxylic acid is 1:1.5 to 3.5. Specifically, the molar ratio can be any one of 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5 or a range formed by any two of the above.

[0050] In a specific embodiment, the organic solvent is selected from N,N-dimethylformamide; the base is selected from triethylamine; the electrolyte is selected from tetrabutylammonium fluoroborate;

[0051] The molar ratio of the triethylamine to the benzene-containing compound is 0.4 to 0.6:1. Specifically, the molar ratio can be any one of 0.4:1, 0.5:1, and 0.6:1, or a range formed by any two of the points; the molar ratio of the tetrabutylammonium fluoroborate to the benzene-containing compound is 1 to 1.4:1. Specifically, the molar ratio can be any one of 1:1, 1.1:1, 1.2:1, 1.3:1, and 1.4:1, or a range formed by any two of the points.

[0052] The catalyst includes catalyst 1 and catalyst 2; the molar ratio of catalyst 1 to catalyst 2 is 1:1;

[0053] The catalyst 1 is ferrous acetate; the catalyst 2 is selected from at least one of copper acetylacetonate, Cu(hfacac)2, 4a, and 4b compounds;

[0054] The structural formulas of the compounds 4a and 4b are as follows:

[0055]

[0056] The molar ratio of the catalyst to the benzene-containing compound is 0.2 to 0.4:1. Specifically, the molar ratio can be any one point value among 0.2:1, 0.3:1, and 0.4:1, or a range value formed by any two point values.

[0057] Under the above conditions, the corresponding N-substituted benzene ring bioisosteres can be prepared.

[0058] Taking aniline (compound 1) as an example, the reaction formula for its reaction with alkyl carboxylic acid (compound 2) to generate N-substituted benzene ring bioisostere (compound 3) is as follows:

[0059]

[0060] The principle of synthesizing N-substituted benzene ring bioisosteres in the present invention is as follows: aromatic amine is firstly Cu I Under the action of alkali, transmetallation occurs to generate Cu I -NHAr species, with Fe n With Cu I -NHAr species are oxidized at the anode by Fe n+1 With Cu II -(NHAr)2 species, carboxylic acid anion and Fe n+1 After complexation, ligand-to-metal charge transfer occurs under light to generate alkyl radicals and regenerate Fe n , the free radicals are Cu II -NHAr species are captured and then reduced and eliminated to generate N-substituted benzene ring bioisosteres and regenerate Cu I -NHAr.

[0061] Example 1

[0062] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (compound 3a), the structure of which is shown below:

[0063]

[0064] The specific preparation steps of the 3a compound are as follows:

[0065] In a 10 mL reaction bottle, p-methylaniline (21.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol, Fe(OAc)2), copper acetylacetonate (8.0 mg, 0.03 mmol, Cu(acac)2), triethylamine (10.1 mg, 0.1 mmol, Et3N), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol, TBABF4), N,N-dimethylformamide (4.0 mL, DMF) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.5 mA, and the reaction mixture was stirred at 6 W. After stirring at 20°C for 10 hours under 390nm violet light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring continued for 5 hours. After the reaction was completed, extraction, drying, filtration, concentration, and separation by column chromatography (PE:EtOAc=7:1, Rf=0.30) gave a yellow liquid 3a (37.0 mg, yield: 80%); 1 H NMR (500MHz, DMSO-d6) δ6.89(d,J=8.2Hz,2H),6.59(d,J=8.4Hz,2H),6.21(s,1H),3.62(s,3H),2.24(s,6H),2.14(s,3H). 13 C NMR (126MHz, DMSO) δ170.0,144.5,129.4,125.1,113.6,53.5,51.5,49.2,35.1,20.1.

[0066] Example 2

[0067] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (compound 3b), the structure of which is shown below:

[0068]

[0069] The specific preparation steps of the 3b compound are as follows:

[0070] In a 10 mL reaction bottle, aniline (18.6 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a yellow liquid 3b (26.0 mg, yield: 60%). 1 H NMR (500MHz, Acetone-d6) δ7.11(td,J=7.4,1.9Hz,2H),6.83–6.73(m,2H),6.72–6.57(m,1H),5.65(s,1H),3.65(s,3H),2.31(s,6H). 13 C NMR (126MHz, Acetone) δ170.6,147.9,129.7,118.1,114.7,54.5,51.8,50.1,36.1.

[0071] Example 3

[0072] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (compound 3c), the structure of which is shown below:

[0073]

[0074] The specific preparation steps of the 3c compound are as follows:

[0075] In a 10 mL reaction bottle, add N-BOC-L-4-aminophenylalanine ethyl ester (61.6 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL), the anode is a carbon cloth electrode, the cathode is a glassy carbon electrode, the current is 2.0 mA, after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, add 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol), and continue stirring for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a yellow liquid 3c (60.5 mg, yield: 70%). 1 H NMR (500MHz, Acetone-d6) δ7.01(d,J=7.9Hz,2H),6.72(d,J=7.9Hz,2H),5.96(d,J=8.0Hz,1H),5.64(s,1H),4.28(q, J=7.8Hz,1H),4.12(h,J=7.6Hz,2H),3.65(s,3H),3.01–2.86(m,3H),2.30(s,6H),1.37(s,9H),1.20(t,J=7.1Hz,3H). 13 C NMR (126MHz, Acetone) δ172.0,169.7,155.3,145.8,129.8,125.7,113.8,78.4,60.4,55.5,50.9,49.3,36.7,35.3,27.6,13.6.

[0076] Example 4

[0077] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (compound 3d), the structure of which is shown below:

[0078]

[0079] The specific preparation steps of the 3d compound are as follows:

[0080] In a 10 mL reaction bottle, ethyl p-aminophenylacetate (35.8 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.5 mA, and after stirring for 10 hours at 20 ° C under 6 W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a yellow liquid 3d (37.6 mg, yield: 62%). 1 H NMR (500MHz, Acetone-d6) δ7.11–7.01(m,2H),6.78–6.69(m,2H),5.67(s,1H),4. 07(q,J=7.1Hz,2H),3.65(s,3H),3.45(s,2H),2.31(s,6H),1.20(t,J=7.1Hz,3H). 13 C NMR (126MHz, Acetone) δ172.3,170.6,146.7,130.6,124.1,114.6,60.8,54.5,51.8,50.1,40.8,36.1,14.5.

[0081] Example 5

[0082] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (compound 3e), the structure of which is shown below:

[0083]

[0084] The specific preparation steps of the 3e compound are as follows:

[0085] In a 10 mL reaction bottle, 4-aminophenylboronic acid pinacol ester (43.8 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a yellow liquid 3e (30.9 mg, yield: 45%). 1 H NMR (500MHz, Acetone-d6) δ7.53(d,J=7.8Hz,2H),6.77(d,J=7.8Hz,2H),3.66(s,3H),2.34(s,6H),1.29(s,12H). 13 C NMR (126MHz, Acetone) δ170.4,150.6,136.9,113.6,83.8,54.6,51.8,49.6,36.2,25.2.

[0086] Example 6

[0087] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3f compound), the structure of which is shown below:

[0088]

[0089] The specific preparation steps of the 3f compound are as follows:

[0090] In a 10 mL reaction bottle, add p-aminobenzyl alcohol (24.6 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL), the anode is a carbon cloth electrode, the cathode is a glassy carbon electrode, the current is 2.0 mA, after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, add 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol), and continue stirring for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a yellow liquid 3f (33.6 mg, yield: 68%). 1 H NMR (500MHz, Acetone-d6) δ7.11(d,J=8.5Hz,2H),6.74(d,J=8.5Hz,2H),5.64(s,1H),4.46(s,2H),3.89(s,1H),3.64(s,3H),2.30(s,6H). 13 CNMR(126MHz,Acetone)δ170.6,146.9,132.2,128.8,114.5,64.7,54.5,51.8,50.2,36.1.

[0091] Example 7

[0092] This example provides an N-substituted bicyclo[1.1.1]pentane (3 g compound), the structure of which is shown below:

[0093]

[0094] The specific preparation steps of the 3g compound are as follows:

[0095] In a 10 mL reaction bottle, 2-aminodiphenyl ether (37.0 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6 W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain 3 g (40.2 mg, yield: 65%) of yellow liquid; 1 H NMR(500MHz, Acetone-d6)δ7.37–7.29(m,2H),7.11(dd,J=8.1,1.5Hz,1H),7.09–7.02(m,2H),6.95–6.86 (m,2H),6.79(dd,J=7.9,1.4Hz,1H),6.68(td,J=7.7,1.5Hz,1H),5.51(s,1H),3.64(s,3H),2.34(s,6H). 13 C NMR (126MHz, Acetone) δ170.4,158.6,143.9,139.8,130.5,125.6,123.4,120.2,118.3,118.1,114.5,54.6,51.8,49.9,36.1.

[0096] Example 8

[0097] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3h compound), the structure of which is shown below:

[0098]

[0099] The specific preparation steps of the 3h compound are as follows:

[0100] In a 10 mL reaction bottle, 2-naphthylamine (28.6 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the mixture was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a yellow liquid 3h (37.4 mg, yield: 60%); 1 H NMR (500MHz, Acetone-d6) δ7.75–7.60 (m, 3H), 7.33 (t, J = 7.2Hz, 1H), 7.19–7. 12(m,2H),7.03(dd,J=8.8,2.3Hz,1H),5.99(s,1H),3.67(s,3H),2.41(s,6H). 13 C NMR (126MHz, Acetone) δ170.59,145.58,136.16,129.48,128.39,126.84,122.66,119.16,106.75,54.50,51.81,50.00,36.27.

[0101] Example 9

[0102] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (compound 3i), the structure of which is shown below:

[0103]

[0104] The specific preparation steps of the 3i compound are as follows:

[0105] In a 10 mL reaction bottle, 2-(4-aminophenyl)-2-methylpropionitrile (32.0 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a white solid 3i (38.1 mg, yield: 67%). 1 H NMR (500MHz, Acetone-d6) δ7.31–7.25(m,2H),6.85–6.78(m,2H),5.85(s,1H),3.65(s,3H),2.33(s,6H),1.65(s,6H). 13 C NMR (126MHz, Acetone) δ170.5,147.3,131.2,126.6,125.6,114.6,54.5,51.8,49.9,36.9,36.2,29.4.

[0106] Example 10

[0107] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (compound 3j), the structure of which is shown below:

[0108]

[0109] The specific preparation steps of the 3j compound are as follows:

[0110] In a 10 mL reaction bottle, 4-chloroaniline (25.5 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a white solid 3j (32.6 mg, yield: 65%). 1 H NMR (500MHz, Acetone-d6) δ7.14–7.09(m,2H),6.82–6.75(m,2H),5.90(s,1H),3.65(s,3H),2.31(s,6H). 13 C NMR (126MHz, Acetone) δ170.4,146.8,129.6,122.2,115.9,54.4,51.8,49.9,36.2.

[0111] Embodiment 11

[0112] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3k compound), the structure of which is shown below:

[0113]

[0114] The specific preparation steps of the 3k compound are as follows:

[0115] In a 10 mL reaction bottle, 4-bromoaniline (34.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a white solid 3k (38.4 mg, yield: 65%). 1 H NMR (500MHz, Acetone-d6) δ7.29–7.20(m,2H),6.79–6.69(m,2H),5.92(s,1H),3.65(s,3H),2.32(s,6H). 13 C NMR (126MHz, Acetone) δ170.4,147.1,132.5,116.4,109.3,54.4,51.8,49.8,36.1.

[0116] Example 12

[0117] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (compound 31), the structure of which is shown below:

[0118]

[0119] The specific preparation steps of the 31 compound are as follows:

[0120] In a 10 mL reaction bottle, 4-fluoroaniline (22.2 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6 W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain yellow liquid 3l (28.7 mg, yield: 61%); 1 H NMR (500MHz, Acetone-d6) δ6.94–6.86(m,2H),6.78(m,2H),5.63(s,1H),3.64(s,3H),2.29(s,6H). 13 C NMR(126MHz,Acetone)δ170.6,156.6(d, 1 JC-F=232.5Hz),144.37,116.0(d, 2 JC-F=22.5Hz),115.7(d, 3 JC-F=7.5Hz),54.4,51.8,50.3,36.0. 19 F NMR(471MHz,Acetone)δ-129.46.

[0121] Example 13

[0122] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3m compound), the structure of which is shown below:

[0123]

[0124] The specific preparation steps of the 3m compound are as follows:

[0125] In a 10 mL reaction bottle, 3,5-dichloroaniline (32.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a white solid 3m (38.3 mg, yield: 67%). 1 H NMR (500MHz, Acetone-d6) δ6.72(d,J=1.8Hz,2H),6.68(t,J=1.7Hz,1H),6.39(s,1H),3.65(s,3H),2.35(s,6H). 13 C NMR (126MHz, Acetone) δ170.2,150.0,135.8,117.1,112.5,54.4,51.9,49.2,36.2.

[0126] Embodiment 14

[0127] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3n compound), the structure of which is shown below:

[0128]

[0129] The specific preparation steps of the 3n compound are as follows:

[0130] In a 10 mL reaction bottle, 4-trifluoromethoxyaniline (35.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain yellow liquid 3n (41.5 mg, yield: 69%); 1 H NMR (500MHz, Acetone-d6) δ7.08 (d, J = 8.5Hz, 2H), 6.88–6.80 (m, 2H), 6.01 (s, 1H), 3.65 (s, 3H), 2.34 (s, 6H). 13 C NMR (126MHz, Acetone) δ170.5,147.1,141.1,123.0,121.7(q, 1 JC-F=252.5Hz),115.00,54.4,51.8,49.8,36.2. 19 FNMR (471MHz, Acetone) δ-59.14.

[0131] Embodiment 15

[0132] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3o compound), the structure of which is shown below:

[0133]

[0134] The specific preparation steps of the 3o compound are as follows:

[0135] In a 10 mL reaction bottle, 4-(trifluoromethylthio)aniline (38.6 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain yellow liquid 3o (38.0 mg, yield: 60%); 1 H NMR (500MHz, Acetone-d6) δ7.47–7.40(m,2H),6.92–6.86(m,2H),6.43(s,1H),3.66(s,3H),2.37(s,6H). 13 C NMR (126MHz, Acetone) δ170.3,150.7,138.9,130.9(q, 1 JC-F=305.0Hz),115.1,109.4,54.5,51.9,49.3,36.3. 19 F NMR (471MHz, Acetone) δ-45.66.

[0136] Example 16

[0137] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3p compound), the structure of which is shown below:

[0138]

[0139] The specific preparation steps of the 3p compound are as follows:

[0140] In a 10 mL reaction bottle, N-BOC-m-phenylenediamine (41.6 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring at 20 ° C for 10 hours under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a yellow liquid 3p (23.2 mg, yield: 35%). 1 H NMR(500MHz, Acetone-d6)δ8.26(s,1H),7.13(s,1H),6.98(t,J=8.0Hz,1H),6.94–6.86(m, 1H),6.37(ddd,J=8.0,2.2,0.9Hz,1H),5.67(s,1H),3.65(s,3H),2.33(s,6H),1.47(s,9H). 13 C NMR (126MHz, Acetone) δ170.6,153.6,148.3,141.3,129.9,109.4,108.1,103.9,79.6,54.5,51.7,50.0,36.2,28.5.

[0141] Embodiment 17

[0142] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3q compound), the structure of which is shown below:

[0143]

[0144] The specific preparation steps of the 3q compound are as follows:

[0145] In a 10 mL reaction bottle, 4-trifluoromethylaniline (32.2 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a yellow liquid 3q (27.4 mg, yield: 48%). 1 H NMR (500MHz, Acetone-d6) δ7.43(d,J=8.6Hz,2H),6.92(d,J=8.6Hz,2H),6.41(s,1H),3.66(s,3H),2.38(s,6H). 13 C NMR(126MHz,Acetone)δ170.30,151.0,127.1(q, 3 JC-F=3.75Hz),126.2(q, 1 JC-F=267.5Hz),118.9(q, 2 JC-F=31.3Hz),113.9,54.5,51.9,49.3,36.3,30.1. 19 F NMR(471MHz,Acetone)δ-61.41.

[0146] Embodiment 18

[0147] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3r compound), the structure of which is shown below:

[0148]

[0149] The specific preparation steps of the 3r compound are as follows:

[0150] In a 10 mL reaction bottle, methyl 4-aminobenzoate (30.2 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6 W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=6:1, Rf=0.30) to obtain a yellow liquid 3r (23.2 mg, yield: 44%). 1 H NMR (500MHz, Acetone-d6) δ7.82–7.75(m,2H),6.86–6.79(m,2H),6.46(s,1H),3.78(s,3H),3.66(s,3H),2.38(s,6H). 13 C NMR (126MHz, Acetone) δ170.3,167.3,152.0,131.9,119.3,113.4,54.6,51.9,51.6,49.3,36.3.

[0151] Embodiment 19

[0152] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3s compound), the structure of which is shown below:

[0153]

[0154] The specific preparation steps of the 3s compound are as follows:

[0155] In a 10 mL reaction bottle, 4-cyanoaniline (23.6 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6 W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a white solid 3s (21.8 mg, yield: 45%); 1 H NMR (500MHz, Acetone-d6) δ7.50–7.43(m,2H),6.92–6.86(m,2H),6.66(s,1H),3.66(s,3H),2.38(s,6H). 13 C NMR (126MHz, Acetone) δ170.2,151.5,134.2,120.6,114.4,99.8,54.5,51.9,49.1,36.3.

[0156] Embodiment 20

[0157] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3t compound), the structure of which is shown below:

[0158]

[0159] The specific preparation steps of the 3t compound are as follows:

[0160] In a 10 mL reaction bottle, 4-methanesulfonylaniline (34.2 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a white solid 3t (30.0 mg, yield: 51%). 1 H NMR (500MHz, Acetone-d6) δ7.68–7.63(m,2H),6.96–6.90(m,2H),6.67(s,1H),3.66(s,3H),2.99(s,3H),2.40(s,6H). 13 C NMR (126MHz, Acetone) δ170.2,152.1,129.8,129.5,113.6,54.5,51.9,49.1,44.9,36.3.

[0161] Embodiment 21

[0162] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3u compound), the structure of which is shown below:

[0163]

[0164] The specific preparation steps of the 3u compound are as follows:

[0165] In a 10 mL reaction bottle, add p-aminophenylacetonitrile (26.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL), the anode is a carbon cloth electrode, the cathode is a glassy carbon electrode, the current is 1.0 mA, after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, add 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol), and continue stirring for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=3:1, Rf=0.30) to obtain a yellow solid 3t (26.6 mg, yield: 52%); 1 H NMR (500MHz, Acetone-d6) δ7.16–7.10(m,2H),6.84–6.77(m,2H),5.82(s,1H),3.76(s,2H),3.65(s,3H),2.32(s,6H). 13 C NMR (126MHz, Acetone) δ170.5,147.4,129.6,120.3,119.,115.0,54.5,54.4,51 8,49.9,36.1,22.55.

[0166] Embodiment 22

[0167] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3v compound), the structure of which is shown below:

[0168]

[0169] The specific preparation steps of the 3v compound are as follows:

[0170] In a 10 mL reaction bottle, 4-(difluoromethoxy)aniline (31.8 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the mixture was extracted, dried, filtered, and concentrated, and the yellow liquid 3v (39.6 mg, yield: 52%) was separated by column chromatography (PE:EtOAc=7:1, Rf=0.30); 1 H NMR (500MHz, Acetone-d6) δ7.00–6.94(m,2H),6.83–6.78(m,2H),6.74(t,J=75.2Hz,1H),5.80(s,1H),3.65(s,3H),2.31(s,6H). 13 C NMR(126MHz,Acetone)δ170.6,145.8,143.7,121.7,118.0(t, 1 JC-F=257.0Hz),115.5,54.5,51.8,50.2,36.1. 19 F NMR(471MHz,Acetone)δ-81.42.

[0171] Embodiment 23

[0172] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3w compound), the structure of which is shown below:

[0173]

[0174] The specific preparation steps of the 3w compound are as follows:

[0175] In a 10 mL reaction bottle, add (S)-indoline-2-carboxylic acid methyl ester (35.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL), the anode is a carbon cloth electrode, the cathode is a glassy carbon electrode, the current is 1.5 mA, after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, add 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol), and continue stirring for 5 hours. After the reaction was completed, the mixture was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a colorless liquid 3w (39.7 mg, yield: 66%). 1 H NMR(500MHz,Chloroform-d)δ7.09–7.01(m,2H),6.74(d,J=7.6Hz,2H),4.28(dd,J=10.4,8.2Hz,1H) ,3.77(s,3H),3.70(s,3H),3.39(dd,J=15.9,10.4Hz,1H),3.06(dd,J=15.9,8.2Hz,1H),2.39(s,6H). 13 C NMR (126MHz, CDCl3) δ1744.0,170.3,148.9,127.7,127.4,124.4,119.2,109.2,63.4,53.1,52.44,52.22,51.9,35.3,33.7.

[0176] Embodiment 24

[0177] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3x compound), the structure of which is shown below:

[0178]

[0179] The specific preparation steps of the 3x compound are as follows:

[0180] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=10:1, Rf=0.30) to obtain a colorless liquid 3x (29.2 mg, yield: 60%); 1 H NMR (500MHz, Acetone-d6) δ7.03 (dt, J=7.2, 1.4Hz, 1H), 6.99 (td, J=7.7, 1.2Hz, 1H), 6.75 (d, J=7 .9Hz,1H),6.63(td,J=7.4,1.0Hz,1H),3.36(t,J=8.4Hz,2H),2.89(d,J=8.5Hz,2H),2.34(s,6H). 13 C NMR (126MHz, Acetone) δ170.5151.1,131.4,127.9,125.2,119.0,109.7,52.8,51.8,50.8,36.0,28.6.

[0181] Embodiment 25

[0182] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3y compound), the structure of which is shown below:

[0183]

[0184] The specific preparation steps of the 3y compound are as follows:

[0185] In a 10 mL reaction bottle, m-methylaniline (21.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring at 20 ° C for 10 hours under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a yellow liquid 3y (32.4 mg, yield: 70%); 1 H NMR (500MHz, Acetone-d6) δ6.99(t,J=7.8Hz,1H),6.61–6.56(m,2H),6.47(d,J=7.4Hz,1H),5.59(s,1H),3.64(s,3H),2.30(s,6H),2.21(s,3H). 13 C NMR (126MHz, Acetone) δ170.6,147.9,139.2,129.6,119.1,115.4,111.9,54.6,51.8,50.1,36.1,21.6.

[0186] Embodiment 26

[0187] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3z compound), the structure of which is shown below:

[0188]

[0189] The specific preparation steps of the 3z compound are as follows:

[0190] In a 10 mL reaction bottle, 2-(dimethylphosphinoyl)aniline (33.8 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (EtOAc, Rf=0.30) to obtain a white solid 3z (46.3 mg, yield: 79%); 1 H NMR(500MHz, Acetone-d6)δ8.38(s,1H),7.36–7.21(m,2H),7.00(dd,J=8.5,4.6 Hz,1H),6.69(t,J=7.5Hz,1H),3.65(s,3H),2.35(s,6H),1.69(d,J=13.4Hz,6H). 13 C NMR (126MHz, Acetone) δ170.4,152.2,152.1,133.4,133.4,131.6,131.6,117.3,117.2,117. 2,117.13,115.91,115.14,114.15,114.09,54.49,51.79,49.23,36.37,29.82,19.04,18.47. 13 C NMR(126MHz,Acetone)δ170.4,152.1(d, 5 JC-P=3.8Hz),133.4(d, 6 JC-P=2.5Hz),131.6(d, 3 JC-P=11.3Hz),117.2(d, 2 JC-P=12.6Hz),115.5(d, 1 JC-P=97.0Hz),114.1(d, 4 JC-P=7.6Hz),54.5,51.8,49.2,364,19.0,18.5. 31 P NMR (202 MHz, Acetone) δ 42.42.

[0191] Embodiment 27

[0192] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3aa compound), the structure of which is shown below:

[0193]

[0194] The specific preparation steps of the 3aa compound are as follows:

[0195] In a 10 mL reaction bottle, 5-amino-2-methylpyridine (21.6 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a white solid 3aa (20.4 mg, yield: 44%). 1 H NMR (500MHz, Acetone-d6) δ8.01(d,J=2.8Hz,1H),7.08(dd,J=8.3,2.9Hz,1H),6.97(d,J=8.3Hz,1H),5.76(s,1H),3.65(s,3H),2.33(s,3H),2.31(s,6H). 13 C NMR (126MHz, Acetone) δ170.5,147.5,141.7,136.7,123.5,121.6,54.4,51.8,50.0,36.0,23.2.

[0196] Embodiment 28

[0197] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3ab compound), the structure of which is shown below:

[0198]

[0199] The specific preparation steps of the 3ab compound are as follows:

[0200] In a 10 mL reaction bottle, 6-bromo-3-aminopyridine (34.6 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a light yellow solid 3ab (41.4 mg, yield: 70%). 1 H NMR (500MHz, Acetone-d6) δ7.89(d,J=3.1Hz,1H),7.27(d,J=8.6Hz,1H),7.16(dd,J=8.6,3.1Hz,1H),6.21(s,1H),3.65(s,3H),2.35(s,6H). 13 C NMR (126MHz, Acetone) δ170.6,143.9,136.8,128.8,128.4,124.1,54.3,51.9,49.4,36.1.

[0201] Embodiment 29

[0202] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3ac compound), the structure of which is shown below:

[0203]

[0204]

[0205] The specific preparation steps of the 3ac compound are as follows:

[0206] In a 10 mL reaction bottle, 2-fluoro-5-aminopyridine (22.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a yellow liquid 3ac (22.2 mg, yield: 47%). 1 H NMR (500MHz, Acetone-d6) δ7.67(s,1H),7.40–7.33(m,1H),6.84(dd,J=8.8,3.4Hz,1H),5.95(s,1H),3.65(s,3H),2.33(s,6H).13C NMR(126MHz,Acetone)δ170.4,157.5(d, 1 JC-F=226.8Hz),142.4(d, 4 JC-F=3.8Hz),132.5(d, 3 JC-F=15.1Hz),127.1(d, 1 JC-F=6.3Hz),109.7(d, 2 JC-F=40.3Hz),54.3,51.8,50.0,36.0. 19 F NMR(471MHz,Acetone)δ-83.62.

[0207] Embodiment 30

[0208] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3ad compound), the structure of which is shown below:

[0209]

[0210] The specific preparation steps of the 3ad compound are as follows:

[0211] In a 10 mL reaction bottle, 2-chloro-5-aminopyridine (25.7 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a light yellow solid 3ac (31.2 mg, yield: 62%). 1 H NMR (500MHz, Acetone-d6) δ7.89(d,J=3.1Hz,1H),7.24(dd,J=8.6,3.1Hz,1H),7.15(d,J=8.6Hz,1H),6.20(s,1H),3.65(s,3H),2.35(s,6H). 13 C NMR (126MHz, Acetone) δ170.3,143.5,139.4,136.1,124.7,124.1,54.3,51.9,49.5,36.1.

[0212] Embodiment 31

[0213] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3ae compound), the structure of which is shown below:

[0214]

[0215] The specific preparation steps of the 3ae compound are as follows:

[0216] In a 10 mL reaction bottle, 3-amino-5-chloropyridine (25.7 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a light yellow solid 3ac (22.6 mg, yield: 45%). 1 H NMR (500MHz, Acetone-d6) δ8.07(s,1H),7.87(s,1H),7.15(t,J=2.2Hz,1H),6.32(s,1H),3.66(s,3H),2.38(s,6H). 13 C NMR (126MHz, Acetone) δ170.2,145.1,137.3,135.7,132.5,119.1,54.4,51.9,49.3,36.1.

[0217] Embodiment 32

[0218] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3af compound), the structure of which is shown below:

[0219]

[0220] The specific preparation steps of the 3af compound are as follows:

[0221] In a 10 mL reaction bottle, 6-methyl-3-amino-2-chloropyridine (28.5 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a light yellow liquid 3af (27.1 mg, yield: 51%). 1 H NMR (500MHz, Acetone-d6) δ7.35(d,J=8.1Hz,1H),7.05(d,J=8.1Hz,1H),5.61(s,1H),3.66(s,3H),2.39(s,6H),2.32(s,3H).13C NMR (126MHz, Acetone) δ170.2,146.7,137.8,136.5,123.3,121.6,54.4,51.9,49.5,36.2,22.7.

[0222] Embodiment 33

[0223] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3af compound), the structure of which is shown below:

[0224]

[0225] The specific preparation steps of the 3ag compound are as follows:

[0226] In a 10 mL reaction bottle, 2-methoxy-3-aminopyridine (24.8 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a light yellow liquid 3ag (22.3 mg, yield: 45%). 1 H NMR (500MHz, Acetone-d6) δ7.44 (dd, J=5.0, 1.6Hz, 1H), 7.11 (dd, J=7.7, 1.6Hz, 1H ),6.77(dd,J=7.6,5.0Hz,1H),5.41(s,1H),3.87(s,3H),3.65(s,3H),2.36(s,6H). 13 C NMR (126MHz, Acetone) δ170.4,153.1,134.2,131.8,117.9,117.3,54.4,53.3,51.8,49.5,36.2.

[0227] Embodiment 34

[0228] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3af compound), the structure of which is shown below:

[0229]

[0230]

[0231] The specific preparation steps of the 3ah compound are as follows:

[0232] In a 10 mL reaction bottle, 5-amino-2-methylpyrimidine (21.8 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a light yellow liquid 3ah (24.2 mg, yield: 52%). 1 H NMR (500MHz, Acetone-d6) δ8.19(s,2H),5.95(s,1H),3.65(s,3H),2.46(s,3H),2.35(s,6H). 13 C NMR (126MHz, Acetone) δ170.3,157.7,142.9,139.5,54.4,51.9,49.6,36.0,24.7.

[0233] Embodiment 35

[0234] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3af compound), the structure of which is shown below:

[0235]

[0236] The specific preparation steps of the 3ai compound are as follows:

[0237] In a 10 mL reaction bottle, aminoglutethimide (46.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a colorless liquid 3ai (41.3 mg, yield: 52%). 1 H NMR (500MHz, Acetone-d6) δ9.47(s,1H),7.11(d,J=8.5Hz,2H),6.78(d,J=8.4Hz,2H),5.77(s,1H),3.64(s,3H),2 .51–2.45(m,1H),2.39–2.28(m,8H),2.21(td,J=12.7,12.2,4.5Hz,1H),1.96–1.81(m,2H),0.82(t,J=7.4Hz,3H). 13 C NMR (126MHz, Acetone) δ176.6,173.1,170.6,146.9,128.8,127.9,114.7,54.6,53.3,51.8,50.9,49.9,36.2,33.6,27.5,9.4.

[0238] Embodiment 36

[0239] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3af compound), the structure of which is shown below:

[0240]

[0241] The specific preparation steps of the 3ai compound are as follows:

[0242] In a 10 mL reaction bottle, benzyl (S)-(3-(4-aminophenyl)-2-((tert-butyloxycarbonyl)amino)propionyl)glycine (85.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added, the anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and the reaction mixture was stirred at 6 W. After stirring at 20°C for 10 hours under 390nm violet light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring continued for 5 hours. After the reaction was completed, extraction, drying, filtration, concentration, and separation by column chromatography (PE:EtOAc=1:1, Rf=0.30) gave a colorless liquid 3aj (51.8 mg, yield: 47%); 1 HNMR (500MHz, Acetone-d6) δ7.64(s,1H),7.46–7.29(m,5H),7.03(d,J=8.2Hz,2H),6.69(d,J=8.1Hz,2H),5.92(d,J=8.6Hz,1H),5.59(s,1H),5.17(s, 2H),4.32(q,J=7.8,6.6Hz,1H),4.06–4.01(m,2H),3.64(s,3H),3.04(dd,J =14.1,5.1Hz,1H),2.78(dd,J=13.9,9.0Hz,1H),2.29(s,6H),1.34(s,9H). 13 C NMR (126MHz, Acetone) δ173.0,170.6,170.4,156.2,146.4,137.1,130.8,129.3 ,128.9,127.2,114.6,79.2,67.0,56.8,54.5,51.850.2,41.7,38.1,36.1,28.5.

[0243] Embodiment 37

[0244] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3af compound), the structure of which is shown below:

[0245]

[0246] The specific preparation steps of the 3ak compound are as follows:

[0247] In a 10 mL reaction bottle, add ((3aR,4R,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-(4-aminophenyl)acetate (83.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL), the anode is a carbon cloth electrode, the cathode is a glassy carbon electrode, 1.0 mA current, after stirring at 20 ° C for 10 hours under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a light yellow solid 3ak (57.3 mg, yield: 53%); 1 H NMR (500MHz, Acetone-d6) δ7.46(d,J=8.0Hz,1H),7.08(d,J=8.1Hz,2H),6.75(d,J=8.0Hz,2H),5.82(d,J=2.6Hz,1H),5.72(s,1H),5.64(d,J= 8.5Hz,1H),4.80(ddd,J=27.1,6.5,2.4Hz,2H),4.36–4.24(m,3H),3.64(s,3H),3.55(d,J=2.7Hz,2H),2.30(s,6H),1.51(s,3H),1.31(s,3H). 13 C NMR (126MHz, Acetone) δ172.0,170.6,163.6,151.2,146.9,142.5,130.7,123.7,114.7 ,114.6,102.9,93.5,85.0,84.9,81.8,64.9,54.5,51.8,50.0,40.7,36.1,27.4,25.4.

[0248] Embodiment 38

[0249] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3a1 compound), the structure of which is shown below:

[0250]

[0251] The specific preparation steps of the 3a1 compound are as follows:

[0252] In a 10 mL reaction bottle, add (5R,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl 2-(4-aminophenyl)acetate (109.4 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL), the anode is a carbon cloth electrode, the cathode is a glassy carbon electrode, the current is 1.5 mA, after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added, and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=2:3, Rf=0.30) to obtain a light yellow solid 3al (69.8 mg, yield: 52%). 1 H NMR (500MHz, Acetone-d6) δ7.19–7.06(m,2H),6.84(s,1H),6.79–6.71(m,2H),6.56(s,1H),6.41(s,2H),6.04–5.97(m,2H),5. 94(d,J=9.4Hz,1H),5.70(s,1H),4.60(d,J=4.6Hz,1H),4.28–4.14(m,2H),3.68–3.64(m,14H),2.84–2.77(m,1H),2.31(s,6H). 13C NMR (126MHz, Acetone) δ174.3,173.2,170.66,153.5,148.8,148.3,146.9,138.1,136.44,133.5,130.7,129.9,123 .8,114.7,110.1,109.3,107.9,102.4,74.2,71.7,60.4,56.3,54.5,53.2,51.8,50.1,45.5,44.5,41.0,39.7,36.1.

[0253] Embodiment 39

[0254] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3am compound), the structure of which is shown below:

[0255]

[0256] The specific preparation steps of the 3am compound are as follows:

[0257] In a 10 mL reaction bottle, (1R, 2S)-2-(2,2-dichloroacetylamino)-3-fluoro-1-(4-(methylsulfonyl)phenyl)propyl 2-(4-aminophenyl) acetate (98.1 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and the reaction mixture was stirred at 6 W. After stirring at 20°C for 10 hours under 390nm violet light irradiation, 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34 mg, 0.2 mmol) was added and stirring continued for 5 hours. After the reaction was completed, extraction, drying, filtration, concentration, and separation by column chromatography (PE:EtOAc=1:1, Rf=0.30) gave yellow solid 3am (51.6 mg, yield: 42%); 1H NMR (500MHz, Acetone-d6) δ8.03(d,J=9.2Hz,1H),7.88(d,J=8.3Hz,2H),7.60(d,J=8.3Hz,2H),7.08(d,J=8.5Hz,2H),6.78–6 .73(m,2H),6.32(s,1H),6.12(d,J=5.1Hz,1H),5.73(s,1H),4.69–4.41(m,3H),3.67–3.58(m,5H),3.09(s,3H),2.31(s,6H). 13 C NMR (126MHz, Acetone) δ171.2,170.5,164.8,147.0,143.9,142.1,130.9,128.4,128.2,123.3,114.7,82.6(d, 1 JC-F=171.4Hz),73.6(d, 3 JC-F=5.0Hz),67.3,54.6(d, 2 JC-F=26.5Hz),54.5,51.8,50.1,44.2,40.6,36.1. 19 F NMR(471MHz,Acetone)δ-76.12.

[0258] Embodiment 40

[0259] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3an compound), the structure of which is shown below:

[0260]

[0261] The specific preparation steps of the 3am compound are as follows:

[0262] In a 10 mL reaction bottle, add (8R,9S,13S,14S,17S)-17-(2-(4-aminophenyl)acetoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-3-benzoate (101.8 mg, 0.2 mmol), 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (68mg, 0.4mmol), ferrous acetate (5.2mg, 0.03mmol), copper acetylacetonate (8.0mg, 0.03mmol), triethylamine (10.1mg, 0.1mmol), tetrabutylammonium fluoroborate (79.2mg, 0.24mmol), N,N-dimethylformamide (4.0mL), anode is carbon cloth electrode, cathode is glassy carbon electrode, 1.0mA current, under 6W 390nm purple light irradiation, 20℃ stirring for 10 hours, add 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (34mg, 0.2mmol), continue stirring for 5 hours. After the reaction is completed, extract, dry, filter, concentrate, and separate by column chromatography (PE:EtOAc=3:2, Rf=0.30) to obtain light yellow solid 3am (44.3mg, yield: 35%); 1 H NMR (500MHz, Acetone-d6) δ8.21–8.13(m,2H),7.75–7.69(m,1H),7.60–7.57(m,2H),7.35(d,J=8.5Hz,1 H),7.13–7.06(m,2H),7.02(dd,J=8.4,2.6Hz,1H),6.95(d,J=2.5Hz,1H),6.83–6.72(m,2H),5.66(s,1H ),4.71–4.65(m,1H),3.65(s,3H),3.49(s,2H),2.88–2.87(m,2H),2.31(s,6H),2.27-2.24(m,1H),2.21 –2.14(m,1H),1.94–1.89(m,1H),1.84–1.80(m,1H),1.79–1.72(m,1H),1.59–1.32(m,8H),0.84(s,3H). 13C NMR (126MHz, Acetone) δ172.3,170.6,165.6,149.9,146.7,138.9,138.6,134.5,130.7,130.7,129.6,127.2,124.4, 122.5,119.7,114.7,83.2,54.5,51.8,50.5,50.2,44.8,43.7,41.1,39.2,37.7,36.1,28.2,27.7,26.8,23.8,12.4.

[0263] Embodiment 41

[0264] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3ao compound), the structure of which is shown below:

[0265]

[0266] The specific preparation steps of the 3ao compound are as follows:

[0267] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-(difluoromethyl)bicyclo[1.1.1]pentane-1-carboxylic acid (64.8 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring at 20 ° C for 10 hours under 6W 390 nm purple light irradiation, 3-(difluoromethyl)bicyclo[1.1.1]pentane-1-carboxylic acid (32.8 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=10:1, Rf=0.30) to obtain yellow liquid 3ao (25.4 mg, yield: 54%). 1 H NMR (500MHz, Acetone-d6) δ7.03 (dt, J=7.2, 1.4Hz, 1H), 6.99 (td, J=7.7, 1.2Hz, 1H), 6.75 (d, J=7 .9Hz,1H),6.63(td,J=7.4,1.0Hz,1H),3.36(t,J=8.4Hz,2H),2.89(d,J=8.5Hz,2H),2.34(s,6H). 13C NMR (126MHz, Acetone) δ151.1,131.5,127.9,125.3,119.1,114.88(t, 1 JC-F=236.9Hz)109.7,53.5,50.8,49.23(t, 3 JC-F=3.8Hz),36.34(t, 2 JC-F=27.7Hz),28.6. 19 F NMR(471MHz,Acetone)δ-122.20.

[0268] Embodiment 42

[0269] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3ap compound), the structure of which is shown below:

[0270]

[0271] The specific preparation steps of the 3ap compound are as follows:

[0272] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-(anilide)bicyclo[1.1.1]pentane-1-carboxylic acid (92.4 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and after stirring for 10 hours at 20 ° C under 6 W 390 nm purple light irradiation, 3-(anilide)bicyclo[1.1.1]pentane-1-carboxylic acid (46.2 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a yellow liquid 3ap (36.5 mg, yield: 60%); 1 H NMR(500MHz, Acetone-d6)δ8.97(s,1H),7.71(d,J=9.7Hz,2H),7.32–7.25(m,2H),7.05(dd,J=12.6,6.9Hz,2H),7.02 –6.96(m,1H),6.76(d,J=7.9Hz,1H),6.63(t,J=7.1Hz,1H),3.36(t,J=8.3Hz,2H),2.89(t,J=8.4Hz,2H),2.41(s,6H).

[0273] Embodiment 43

[0274] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3aq compound), the structure of which is shown below:

[0275]

[0276] The specific preparation steps of the 3ap compound are as follows:

[0277] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-(phenyl)bicyclo[1.1.1]pentane-1-carboxylic acid (75.2 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light, 3-(phenyl)bicyclo[1.1.1]pentane-1-carboxylic acid (37.6 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=10:1, Rf=0.30) to obtain a white solid 3ap (20.9 mg, yield: 40%). 1 H NMR (500MHz, Acetone-d6) δ7.11(td,J=7.4,1.9Hz,2H),6.83–6.73(m,2H),6.72–6.57(m,1H),5.65(s,1H),3.65(s,3H),2.31(s,6H). 13 C NMR (126MHz, Acetone) δ170.6,147.9,129.7,118.1,114.7,54.5,51.8,50.1,36.1.\

[0278] Embodiment 44

[0279] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3ar compound), the structure of which is shown below:

[0280]

[0281] The specific preparation steps of the 3ar compound are as follows:

[0282] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-((tert-butyldimethylsilyloxy)methyl)bicyclo[1.1.1]pentane-1-carboxylic acid (102.4 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-((tert-butyldimethylsilyloxy)methyl)bicyclo[1.1.1]pentane-1-carboxylic acid (51.2 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=20:1, Rf=0.30) to obtain a white solid 3ar (30.9 mg, yield: 47%). 1 H NMR (500MHz, Acetone-d6) δ7.01(d,J=7.2Hz,1H),6.96(t,J=7.4Hz,1H),6.73(d,J=7.9Hz,1H),6.59(td,J=7.4 ,1.0Hz,1H),3.76(s,2H),3.34(t,J=8.4Hz,2H),2.86(d,J=8.4Hz,2H),1.96(s,6H),0.92(s,9H),0.07(s,6H). 13 C NMR (126MHz, Acetone) δ151.6,131.4,127.8,125.1,118.6,109.6,63.0,53.3,50.9,49.9,38.0,28.6,26.3,18.9,-5.2.

[0283] Embodiment 45

[0284] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3as compound), the structure of which is shown below:

[0285]

[0286] The specific preparation steps of the 3as compound are as follows:

[0287] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-(cyano)bicyclo[1.1.1]pentane-1-carboxylic acid (54.8 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(cyano)bicyclo[1.1.1]pentane-1-carboxylic acid (27.4 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=10:1, Rf=0.30) to obtain a yellow liquid 3as (23.1 mg, yield: 47%); 1 H NMR (500MHz, Acetone-d6) δ7.05(d,J=7.2Hz,1H),7.00(t,J=7.7Hz,1H),6.74(d,J=7.8H z,1H),6.66(t,J=7.3Hz,1H),3.36(t,J=8.4Hz,2H),2.89(t,J=8.4Hz,2H),2.60(s,6H). 13 C NMR (126MHz, Acetone) δ150.5,131.4,127.9,125.4,119.5,118.4,109.6,55.4,50.7,28.5,22.0.

[0288] Embodiment 46

[0289] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3at compound), the structure of which is shown below:

[0290]

[0291] The specific preparation steps of the 3at compound are as follows:

[0292] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-(4-phenylpiperazine-1-carbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (120.0 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(4-phenylpiperazine-1-carbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (60.0 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=1:1, Rf=0.30) to obtain a colorless liquid 3at (38.0 mg, yield: 51%). 1 H NMR (500MHz, Acetone-d6) δ7.24(dd,J=8.7,7.2Hz,2H),7.03(d,J=7.3Hz,1H),6.98(d,J=7.9Hz,3H),6.83(t,J=7.3Hz,1H),6.79(d,J=7.9Hz,1H),6.63 (t,J=7.3Hz,1H),3.84(t,J=5.1Hz,2H),3.69(t,J=5.1Hz,2H),3.37(t,J=8 .4Hz,2H),3.17(dt,J=28.2,5.1Hz,4H),2.88(d,J=8.3Hz,2H),2.44(s,6H). 13 C NMR(126MHz,Acetone)δ167.7,152.3,151.2,131.4,129.8,127.8,125.2,120 .6,118.9,117.2,109.,53.8,53.7,50.8,50.4,49.9,46.3,42.6,38.1,28.6.

[0293] Embodiment 47

[0294] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3au compound), the structure of which is shown below:

[0295]

[0296] The specific preparation steps of the 3at compound are as follows:

[0297] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-(tert-butylaminocarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (84.4 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 3-(tert-butylaminocarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (42.2 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=10:1, Rf=0.30) to obtain a colorless liquid 3au (25.0 mg, yield: 44%). 1 H NMR (500MHz, Acetone-d6) δ7.02(d,J=7.3Hz,1H),6.97(t,J=7.7Hz,1H),6.71(d,J=7.8Hz,1H),6.61( t,J=7.4Hz,1H),6.51(s,1H),3.32(t,J=8.3Hz,2H),2.86(t,J=8.3Hz,2H),2.24(s,6H),1.32(s,9H). 13 C NMR (126MHz, Acetone) δ169.4,151.3,131.4,127.8,125.2,118.8,109.6,52.1,51.8,51.31,50.8,38.3,28.9,28.6.

[0298] Embodiment 48

[0299] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3av compound), the structure of which is shown below:

[0300]

[0301] The specific preparation steps of the 3av compound are as follows:

[0302] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-(tert-butoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (84.8 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and after stirring at 20 ° C for 10 hours under 6W 390 nm purple light irradiation, 3-(tert-butoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (84.8 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=10:1, Rf=0.30) to obtain a white solid 3av (28.5 mg, yield: 50%); 1 H NMR (500MHz, Acetone) δ7.04,7.02,7.00,6.98,6.97,6.75,6.73,6.64,6.63,6.61,3.36,3.35,3.33,2.90,2.88,2.86,2.28,2.05,1.44. 13 C NMR (126MHz, Acetone) δ169.6,151.2,131.4,127.9,125.2,119.0,109.6,80.7,52.6,52.5,50.8,37.0,28.6,28.1.

[0303] Embodiment 49

[0304] This embodiment provides an N-substituted bicyclo[2.2.2]octane (3aw compound), the structure of which is shown below:

[0305]

[0306] The specific preparation steps of the 3aw compound are as follows:

[0307] In a 10 mL reaction bottle, p-methylaniline (21.4 mg, 0.2 mmol), 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid (84.8 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid (42.4 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a yellow liquid 3aw (29.5 mg, yield: 54%). 1 H NMR (500MHz, Acetone-d6) δ6.88(d,J=8.1Hz,2H),6.72–6.67(m,2H),3.59(s,3H),2.16(s,3H),1.91–1.78(m,12H). 13 C NMR (126MHz, Acetone) δ177.9,145.5,129.9,127.5,119.0,52.2,51.8,39.2,31.9,29.6,20.4. 13 C NMR (126MHz, Acetone) δ168.5,151.2,140.0,131.5,129.4,127.8,125.2,124.3,120.4,119.0,109.6,52.4,52.1,50.9,38.6,28.6.

[0308] Embodiment 50

[0309] This embodiment provides an N-substituted bicyclo[2.2.1]heptane (3ax compound), the structure of which is shown below:

[0310]

[0311] The specific preparation steps of the 3ax compound are as follows:

[0312] In a 10 mL reaction bottle, p-methylaniline (21.4 mg, 0.2 mmol), 4-(methoxycarbonyl)bicyclo[2.2.1]heptane-1-carboxylic acid (79.2 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and after stirring at 20 ° C for 10 hours under 6W 390 nm purple light irradiation, 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid (39.6 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=7:1, Rf=0.30) to obtain a yellow liquid 3aw (25.9 mg, yield: 50%); 1 H NMR(500MHz,Chloroform-d)δ6.98(d,J=8.0Hz,2H),6.65(d,J=8.1Hz,2H),3.69( s,3H),2.24(s,3H),2.14–2.06(m,2H),1.95(d,J=8.4Hz,4H),1.84–1.66(m,4H). 13 C NMR (126MHz, CDCl3) δ176.2,144.6,129.8,128.2,117.1,65.5,51.9,50.2,46.5,34.5,33.3,20.7.

[0313] Embodiment 51

[0314] This embodiment provides an N-substituted bicyclo[2.1.1]pentane (3ay compound), the structure of which is shown below:

[0315]

[0316] The specific preparation steps of the 3ay compound are as follows:

[0317] In a 10 mL reaction bottle, p-methylaniline (21.4 mg, 0.2 mmol), 4-(phenyl)bicyclo[2.1.1]hexane-1-carboxylic acid (80.8 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light, 4-(phenyl)bicyclo[2.1.1]hexane-1-carboxylic acid (40.4 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=10:1, Rf=0.30) to obtain a yellow liquid 3ay (24.7 mg, yield: 47%). 1 H NMR(500MHz,Chloroform-d)δ7.37–7.32(m,2H),7.28(dd,J=8.2,1.4Hz,2H),7.23(tt,J= 6.7,1.3Hz,1H),7.02(d,J=8.0Hz,2H),6.70–6.66(m,2H),2.27(s,3H),2.06–1.94(m,8H). 13 C NMR (126MHz, Chloroform-d) δ143.8,143.1,129.1,127.7 127.0,125.6,125.42 115.0,60.6,47.0,34.2,31.1,19.9.

[0318] Embodiment 52

[0319] This embodiment provides an N-substituted bicyclo[2.1.1]pentane (3az compound), the structure of which is shown below:

[0320]

[0321] The specific preparation steps of the 3az compound are as follows:

[0322] In a 10 mL reaction bottle, p-methylaniline (21.4 mg, 0.2 mmol), 4-(4-fluorophenyl)bicyclo[2.1.1]hexane-1-carboxylic acid (88.0 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added. The anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.5 mA, and after stirring for 10 hours at 20 ° C under 6W 390 nm purple light irradiation, 4-(4-fluorophenyl)bicyclo[2.1.1]hexane-1-carboxylic acid (44.0 mg, 0.2 mmol) was added and stirring was continued for 5 hours. After the reaction was completed, the product was extracted, dried, filtered, concentrated, and separated by column chromatography (PE:EtOAc=10:1, Rf=0.30) to obtain a yellow liquid 3az (23.6 mg, yield: 42%). 1 H NMR (500MHz, Chloroform-d) δ7.22(dd,J=8.5,5.6Hz,2H),7.01(t,J=8.4Hz,4H),6.67(d,J=8.0Hz,2H),2.27(s,3H),2.04–1.91(m,8H). 13 C NMR (126MHz,CDCl3)δ161.4(d, 1 JC-F=244.4Hz),144.30,139.36(d, 4 JC-F=2.5Hz),129.66,127.53,127.4(d, 3 JC-F=7.6Hz),115.50,115.0(d, 2 JC-F=21.4Hz),77.0,61.0,47.8,46.9,34.8,31.7,20.4. 19 F NMR (471MHz,CDCl3)δ-116.92.

[0323] Embodiment 51

[0324] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3ba compound), the structure of which is shown below:

[0325]

[0326] The specific preparation steps of the 3ba compound are as follows:

[0327] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)carbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (117.6 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added, the anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 1.0 mA, and the reaction mixture was stirred at 6 W. After stirring at 20°C for 10 hours under 390nm violet light irradiation, 3-((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)carbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (58.8 mg, 0.2 mmol) was added and stirring continued for 5 hours. After the reaction was completed, extraction, drying, filtration, and concentration were performed, and 3ba (30.0 mg, yield: 41%) was separated by column chromatography (PE:EtOAc=10:1, Rf=0.30); 1 H NMR (500MHz, Acetone-d6) δ7.03(d,J=7.2Hz,1H),6.99(t,J=7.7Hz,1H),6.75(d,J=7.9Hz,1H),6. 63(t,J=7.4Hz,1H),4.67(td,J=10.9,4.4Hz,1H),3.36(t,J=8.4Hz,2H),2.91–2.87(m,2H),2.33( d,J=1.0Hz,6H),1.97–1.85(m,2H),1.69(dt,J=13.4,3.9Hz,2H),1.54–1.38(m,2H),1.11(qd,J=1 3.3,12.7,3.6Hz,1H),0.99(q,J=11.8Hz,1H),0.91(dd,J=6.9,5.6Hz,7H),0.78(d,J=7.0Hz,3H). 13 C NMR(126MHz,Acetone)δ169.6,151.1,131.4,127.9,125.2,119.0,109.7,74.6,5 2.8,52.7,50.8,47.8,41.6,36.3,34.9,32.1,28.6,27.3,24.5,22.3,20.9,17.0.

[0328] Embodiment 52

[0329] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (3bb compound), the structure of which is shown below:

[0330]

[0331] The specific preparation steps of the 3bb compound are as follows:

[0332] In a 10 mL reaction bottle, indoline (23.8 mg, 0.2 mmol), 3-(3,7-dimethyl-6-octenyloxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (117.6 mg, 0.4 mmol), ferrous acetate (5.2 mg, 0.03 mmol), copper acetylacetonate (8.0 mg, 0.03 mmol), triethylamine (10.1 mg, 0.1 mmol), tetrabutylammonium fluoroborate (79.2 mg, 0.24 mmol), N,N-dimethylformamide (4.0 mL) were added, the anode was a carbon cloth electrode, the cathode was a glassy carbon electrode, the current was 2.0 mA, and the reaction mixture was stirred at 6 W. After stirring at 20°C for 10 hours under 390nm violet light irradiation, 3-(3,7-dimethyl-6-octenyloxycarbonyl)carbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (58.8 mg, 0.2 mmol) was added and stirring continued for 5 hours. After the reaction was completed, extraction, drying, filtration, concentration, and column chromatography (PE:EtOAc=10:1, Rf=0.30) was used to separate 3bb (29.4 mg, yield: 40%); 1 H NMR (500MHz, Acetone-d6) δ7.03(d,J=7.2Hz,1H),6.99(t,J=7.5Hz,1H),6.75(d,J=7.8Hz,1H),6.6 3(t,J=7.4Hz,1H),5.14–5.09(m,1H),4.13(td,J=6.7,4.0Hz,2H),3.36(t,J=8.4Hz,2H),2.34(s,6 H),1.99(td,J=16.7,14.4,9.4Hz,2H),1.73–1.68(m,1H),1.67(s,3H),1.61(s,3H),1.58(t,J=7.0 Hz,1H),1.47(dt,J=12.8,6.3Hz,1H),1.42–1.37(m,1H),1.24–1.19(m,1H),0.93(d,J=6.6Hz,3H). 13 C NMR(126MHz,Acetone)δ170.1,151.1,131.6,131.4,127.9,125.4,125.2,11 9.0,109.6,63.4,52.7,50.8,37.6,36.1,30.2,28.6,26.0,25.9,19.8,17.7.

[0333] Embodiment 53

[0334] This embodiment provides an N-substituted bicyclo[1.1.1]pentane (compound 3a), the structure of which is shown below:

[0335]

[0336] The yield of the compound 3a prepared under different conditions was investigated, and the specific preparation steps were basically the same as those in Example 1, except that the conditions in Table 1 below were changed. Experimental Group 1 was used to prepare compound 3a under the same conditions as in Example 1, and Experimental Groups 2-15 were used to prepare compound 3a by changing some of the conditions.

[0337] Table 1

[0338]

[0339] In Table 1, the structural formulas of compound 4a and compound 4b are as follows:

[0340]

[0341] The yield results of each experimental group are shown in Table 1. The comparison between experimental group 1 and experimental groups 2-3 shows that when the catalyst is only Fe(OAc)2 or Cu(acac)2, no 3a compound can be obtained. The comparison between experimental group 3 and experimental groups 4-9 shows that when Fe(OAc)2 in the catalyst is replaced by other types, no 3a compound can be obtained. The comparison between experimental group 3 and experimental groups 10-11 shows that when the anode material used is replaced by a glassy carbon electrode, only a trace amount of 3a compound is obtained; when the cathode material used is replaced by a foamed nickel electrode, the yield of the 3a compound is significantly reduced compared with Example 3. The comparison between experimental group 11 and experimental groups 12-15 shows that when Cu(acac)2 in the catalyst is replaced by other types, the yield of the 3a compound is significantly reduced compared with Example 11.

[0342] Comparative Example 1

[0343] This comparative example provides a method for preparing N-substituted bicyclo[1.1.1]pentane (compound 3a), which is different from the method of experimental group 1 in Example 53 in that no ultraviolet light irradiation is performed in this comparative example. The results show that when no ultraviolet light irradiation is performed, the yield of compound 3a is 0.

[0344] Comparative Example 2

[0345] This comparative example provides a method for preparing N-substituted bicyclo[1.1.1]pentane (compound 3a), which is different from the preparation method of experimental group 1 in Example 53 in that no electrochemical treatment is performed in this comparative example, that is, the current used is 0 mA. It is found that when no electrochemical treatment is performed, the yield of compound 3a is only a trace amount.

[0346] The above description of the embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. An N-substituted benzene ring bioisostere, characterized in that: Including any one of N-substituted bicyclo[1.1.1]pentane, N-substituted bicyclo[2.1.1]pentane, N-substituted bicyclo[2.2.1]heptane, N-substituted bicyclo[2.2.2]octane; The structure of the N-substituted bicyclo[1.1.1]pentane is shown in Formula I, Formula II or Formula III; the structure of the N-substituted bicyclo[2.1.1]pentane is shown in Formula IV; the structure of the N-substituted bicyclo[2.2.2]octane is shown in Formula V; the structure of the N-substituted bicyclo[2.2.1]heptane is shown in Formula VI; Among them, R 1 is hydrogen, methyl, N-BOC-L-alanine, ethyl acetate, pinacol borate, hydroxymethyl, α,α-dimethylacetonitrile, acetonitrile, halogen, difluoromethoxy, trifluoromethoxy, trifluoromethylthio, trifluoromethyl, methyl formate, 4-cyano, 4-methylsulfonyl, benzyl (S)-(2-((tert-butyloxycarbonyl)amino)propionyl)glycine, 3-ethylpiperidine-2,6-dione, (5R,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl any one of: acetate, (1R,2S)-2-(2,2-dichloroacetylamino)-3-fluoro-1-(4-(methylsulfonyl)phenyl)propyl acetate, ((3aR,4R,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl acetate, and (8R,9S,13S,14S,17S)-17-acetoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-benzoate; R 2 Any one of hydrogen, methyl, NHBoc, and halogen; R 3 Any one of hydrogen, dimethylphosphine, and phenoxy; R 4 Any of hydrogen and halogen; R 5 is any one of hydrogen, halogen, and methoxy; R 6 is any of carbon or nitrogen atoms; R 7 is any of carbon or nitrogen atoms; R 8 is either hydrogen or methyl formate; R 9 Any one of difluoromethyl, phenyl, (tert-butyldimethylsilyloxy)methyl, cyano, formanilide, 4-phenylpiperazine-1-carbonyl, tert-butylaminoformyl, tert-butoxycarbonyl, (((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)carbonyl, and 3,7-dimethyl-6-octenyloxycarbonyl; R 10 It is any of hydrogen and halogen.

2. A method for preparing an N-substituted benzene ring bioisostere, characterized in that: The following steps are involved: In the presence of an organic solvent, a base, an electrolyte and a catalyst, a benzene-containing compound reacts with an alkyl carboxylic acid under photocatalytic and electrochemical conditions to generate an N-substituted benzene ring bioisostere.

3. The method for preparing an N-substituted benzene ring bioisostere according to claim 2, characterized in that: The specific steps of the preparation method are: In a reaction container, a benzene compound, an organic solvent, a catalyst, an alkali, an electrolyte, and a part of alkyl carboxylic acids are added, a carbon cloth electrode is used as an anode, and a glassy carbon or nickel foam electrode is used as a cathode, and the mixture is stirred at 20 to 25° C. for 8 to 12 hours under 1 to 3 mA current and irradiation with ultraviolet light; then the remaining alkyl carboxylic acids are added and stirring is continued for 3 to 6 hours to obtain an N-substituted benzene ring bioisostere.

4. The method for preparing an N-substituted benzene ring bioisostere according to claim 3, characterized in that: The benzene-containing compound is selected from p-methylaniline, aniline, N-BOC-L-4-aminophenylalanine ethyl ester, ethyl p-aminophenylacetate, 4-aminophenylboronic acid pinacol ester, p-aminobenzyl alcohol, 2-aminodiphenyl ether, 2-naphthylamine, 2-(4-aminophenyl)-2-methylpropionitrile, 4-chloroaniline, 4-bromoaniline, 4-fluoroaniline, 3,5-dichloroaniline, 4-trifluoromethoxyaniline, 4-(trifluoromethylthio)aniline, N-BOC-m-phenylenediamine, 4-trifluoromethylaniline, 4-aminobenzoic acid methyl ester, 4-cyanoaniline, 4-methylsulfonylaniline, p-aminophenylacetonitrile, 4-(difluoromethoxy)aniline, (S)-indoline-2-carboxylic acid methyl ester, m-methylaniline , 2-(dimethylphosphino)aniline, 5-amino-2-methylpyridine, 6-bromo-3-aminopyridine, 2-fluoro-5-aminopyridine, 2-chloro-5-aminopyridine, 3-amino-5-chloropyridine, 6-methyl-3-amino-2-chloropyridine, 2-methoxy-3-aminopyridine, 5-amino-2-methylpyrimidine, aminoglutethimide, benzyl (S)-(3-(4-aminophenyl)-2-((tert-butyloxycarbonyl)amino)propionyl)glycine, ((3aR,4R,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetracycline trahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-(4-aminophenyl)acetate, (5R,5aR,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofur o[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl At least one of (1R,2S)-2-(2,2-dichloroacetylamino)-3-fluoro-1-(4-(methylsulfonyl)phenyl)propyl 2-(4-aminophenyl)acetate, (8R,9S,13S,14S,17S)-17-(2-(4-aminophenyl)acetoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-3-benzoate, indoline and p-methylaniline.

5. The method for preparing an N-substituted benzene ring bioisostere according to claim 3, characterized in that: The alkyl carboxylic acid is selected from 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid, 3-(difluoromethyl)bicyclo[ 1.1.1]pentane-1-carboxylic acid, 3-(carboxanilide)bicyclo[1.1.1]pentane-1-carboxylic acid, 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid, 4-(methoxycarbonyl)bicyclo[2.2.1]heptane-1-carboxylic acid, 4-(phenyl)bicyclo[ 2.1.1] at least one of hexane-1-carboxylic acid.

6. The method for preparing an N-substituted benzene ring bioisostere according to any one of claims 3 to 5, characterized in that: The molar ratio of the benzene-containing compound to the alkyl carboxylic acid is 1:1.5 to 3.

5.

7. The method for preparing an N-substituted benzene ring bioisostere according to claim 3, characterized in that: The organic solvent is selected from N,N-dimethylformamide; The base is selected from triethylamine; The electrolyte is selected from tetrabutylammonium fluoroborate.

8. The method for preparing an N-substituted benzene ring bioisostere according to claim 3, characterized in that: The catalyst includes catalyst 1 and catalyst 2; The catalyst 1 is ferrous acetate; the catalyst 2 is selected from at least one of copper acetylacetonate, Cu(hfacac)2, 4a, and 4b compounds; The structural formulas of the compounds 4a and 4b are as follows:

9. The method for preparing an N-substituted benzene ring bioisostere according to claim 3, 7 or 8, characterized in that: The molar ratio of the catalyst to the benzene-containing compound is 0.2 to 0.4:1; The molar ratio of triethylamine to the benzene-containing compound is 0.4 to 0.6:1; The molar ratio of the tetrabutylammonium fluoroborate to the benzene-containing compound is 1 to 1.4:

1.

10. The method for preparing N-substituted benzene ring bioisosteres according to claim 3, characterized in that: The power of the purple light is 4-8W and the wavelength is 390nm.

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