Method for photo-promoted direct denitration functionalization of nitroarene compounds and applications thereof

Abstract

The application discloses a method for directly denitro-functionalization of nitroaromatic compounds by light and application, and the method comprises the following steps: using a first monomer selected from a nitroheteroaromatic compound shown in a structure of formula I and a second monomer selected from a phosphonylation reagent, a hydrogenation reagent, a deuteriation reagent, a halogenation reagent or a carbonation reagent as raw materials, irradiating the nitroheteroaromatic compound directly to generate a compound shown in a structure of formula II under the protection of argon at room temperature in an organic solvent, wherein FG is selected from H, D, Cl, Br, C or P. The application has the advantages of simple operation, cheap and easily available raw materials, mild reaction conditions, excellent yield, good compatibility of substrate functional groups, scalable reaction scale, environmental friendliness in the reaction process, no pollution and the like, and has industrial application prospects. The application is suitable for many molecules with biological activity, and can be applied to synthesis and modification of drug molecules, deuterium labeling of aromatic compounds and the like.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology. More specifically, it relates to a method and application of photo-promoted direct denitration of nitroaromatic compounds. Background Technology

[0002] Nitroaromatics are readily available bulk chemicals that can serve as general starting materials for a range of synthetic reactions. However, due to C... Ar The inertness of the -NO2 bond makes direct denitration substitution reactions with unactivated nitroaromatics challenging. Previously, chemists typically relied on two methods to achieve the transformation of the nitro functional group in nitroaromatics. The first method involves a three-step chemical reaction: first, the nitroaromatic is reduced to an aromatic amine; then, the aromatic amine reacts with nitrous acid at low temperature to form a diazonium salt; finally, through the Sandemer reaction, the diazonium salt, catalyzed by cuprous salts (such as CuCl, CuBr, CuCN), has its diazonium group replaced by chlorine, bromine, or cyano functional groups. Synthesis ,2001, 585-590.; Synthesis ,2007, 2534-2538; J. Org. Chem. ,2008, 73 , 316-319; Org. Lett. ,2008, 10 , 3961-3964; Org. Lett. 2024 26 , 7555-7559). Through this series of steps, C Ar -NO2 bonds can be converted to C. Ar -X bonds (X = Cl, Br, I, and CN) and C Ar-O bond (forming phenolic compounds). Although this three-step process is highly efficient and an important method for preparing aryl halides and nitriles, actual production often suffers from low atom utilization, large amounts of waste, and the formation of explosive diazonium salt intermediates. While Ritter et al. designed an optimized, safety-enhanced variant of the Sandmayer reaction, controlling the rate of nitrate reduction to nitrite to change the diazonium salt intermediate formation from an "accumulation-consumption" model to a "formation-immediate consumption" model, reducing the risk of diazonium salt explosion, this method requires the consumption of a stoichiometric amount of cuprous salt and also has limitations in substrate compatibility. The second method involves aromatic nucleophilic substitution reactions, where the nucleophile attacks the nitro-linked aromatic ring carbon, replacing the nitro group and causing it to leave the ring. Unlike SN2 / SN1 reactions on saturated carbon, the stability of aromatic rings necessitates specific activation conditions for this reaction. Aromatic nucleophilic substitution reactions of nitroaromatics typically proceed via an addition-elimination mechanism, where the nucleophile attacks the aromatic ring, forming a crucial σ-complex intermediate. Because electron-withdrawing functional groups at the ortho / para positions of the aromatic ring can stabilize the intermediate, the reaction requires the presence of electron-withdrawing groups at these positions. If no electron-withdrawing groups are present, extreme conditions are required for the reaction to proceed. Therefore, the range of nitroaromatics suitable for aromatic nucleophilic substitution reactions is very limited. Both of the aforementioned methods for transforming the nitro functional group in nitroaromatics have their own problems and limitations. Therefore, from C... Ar -NO2 is directly converted to C. Ar -FGs (FG, functional groups) have always been a long-standing and unresolved problem. Summary of the Invention

[0003] Based on the above facts, the purpose of this invention is to provide a method and application for the direct denitrification of nitroaromatic compounds promoted by light, thereby achieving the photocatalytic denitrification of metal-free nitroaromatic compounds C Ar -NO2 bond to C Ar -P key, C Ar -H / D key, C Ar -Cl / Br bond and C Ar A one-step conversion of the -C key.

[0004] To achieve the above objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides a method for photo-promoted direct denitration of nitroaromatic compounds, the method comprising the following steps: The first monomer is selected from nitro-heteroaromatic hydrocarbons with the structure shown in Formula I. I, and The second monomer is selected from phosphonylating agents, hydrogenating agents, deuterating agents, halogenating agents, or carbonizing agents. As raw materials, In an organic solvent, under room temperature and argon protection, light irradiation is used to directly denitrate the nitro aromatic hydrocarbon to generate a compound with the structure shown in Formula II: II in, FG is selected from H, D, Cl, Br, C or P; X is selected from S, O, NH or NR. 2 ; The R 2 Selected from alkyl, aryl, or heteroaryl groups; The R is selected from alkyl, alkenyl, alkynyl, aryl, heteroaryl, halogen, hydroxyl, amino, alkoxy, ester, amide, or, wherein at least one hydrogen atom is substituted in the aforementioned alkyl, alkenyl, alkynyl, aryl, or heteroaryl groups.

[0005] Wherein, when the second monomer is selected from a phosphonylating agent, FG is P; when the second monomer is selected from a hydrogenating agent, FG is H; when the second monomer is selected from a deuterating agent, FG is D; when the second monomer is selected from a halogenating agent, FG is Cl or Br; when the second monomer is selected from a carbonizing agent, FG is C.

[0006] Further, the nitroheroaryle is selected from nitrothiophenes (e.g., methyl 5-chloro-4-nitrothiophene-2-carboxylate, 3-(5-nitrothiophene-2-yl)pyridine, 5-nitrothiophene-2-carboxylate-( S )-3,7-dimethylhept-6-en-1-yl ester, 3-(5-nitrothiophen-2-yl)pyridine, ((3 aR 4 S 5 R 6 aS )-5-benzoyloxy-2-oxohexahydro-2 H -Cyclopenta[ b ]furan-4-yl)methyl-5-nitrothiophen-2-carboxylate, 5-nitrothiophen-2-carboxylate, 4-bromo-5-nitrothiophen-2-carboxylate, methyl 5-chloro-4-nitrothiophen-2-carboxylate, (1 R ,2 R 4 R)-1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-5-nitrothiophene-2-carboxylic acid ester, 4-bromo-5-nitrothiophene-2-carboxylon, methyl 5-nitrothiophene-2-carboxylate, 2-nitrothiophene, etc.), nitrofurans (e.g., methyl 5-nitrofuran-2-carboxylic acid ester, (5-nitrofuran-2-yl)methanol, 5-nitrofuran-2-onitrile, 3-bromo-2-nitrofuran, 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionic acid-5-nitrofuran 2-ylmethyl ester, 4-(5-nitrofuran-2-yl)quinoline, 3,7-dimethyl octyl 5-nitrofuran-2-carboxylic acid, 6-(3-(adamantane-1-yl)-4-methoxyphenyl)-2-naphthoic acid (5-nitrofuran-2-yl)methyl, 4-(5-nitrofuran-2-yl)quinoline, N-(2-morpholinoethyl)-4-(5-nitrofuran-2-yl)benzamide, (5-nitrofuran-2-carbonyl)tryptophan methyl ester, etc., nitropyrrole (e.g., 5-nitro-1-yl) H methyl pyrrole-2-carboxylate, 5-nitro-1 H methyl pyrrole-2-carboxylate, etc.), nitrobenzylthiophene, nitrobenzylfuran, or nitroindole (e.g., 2-(2-fluoro-1,1'-biphenyl-4-yl)-1-(3-nitro-1-yl) H (-Indol-1-yl)prop-1-one, etc.).

[0007] Furthermore, the phosphonylating agent is selected from trialkoxyphosphite, and its structural formula is shown in Formula III below: III Wherein, the R 1 Selected from C1-C10 alkyl, C5-C10 heteroaryl, and aryl groups.

[0008] Furthermore, the heteroaryl group of C5-C10 is a five-membered heteroaryl or a six-membered heteroaryl.

[0009] Furthermore, the trialkoxyphosphite is selected from triisopropyl phosphite, tribenzyl phosphite, etc.

[0010] Furthermore, the hydrogenating agent is selected from 1,3-dimethylimidazol-2-methyleneborane.

[0011] Furthermore, the deuterating agent is selected from 1,3-dimethylimidazol-2-methylenedeuteronane.

[0012] Furthermore, the carbonizing agent is selected from tert-butane iodo.

[0013] Furthermore, the halogenating agent is selected from chlorinating agents or brominating agents.

[0014] Furthermore, the chlorinating agent is selected from N-chlorosuccinimide.

[0015] Furthermore, the brominating agent is selected from N-bromosuccinimide.

[0016] Furthermore, the second monomer is selected from phosphonylating agents, hydrogenating agents, or deuterating agents, and the molar ratio of the first monomer to the second monomer is 1:2.

[0017] Furthermore, the second monomer is a halogenating agent, and the molar ratio of the first monomer to the second monomer is 1:(1-2).

[0018] Furthermore, the second monomer is a carbonizing agent, and the molar ratio of the first monomer to the second monomer is 1:(2-5).

[0019] Furthermore, the organic solvent is selected from isopropanol, acetonitrile, or dichloromethane.

[0020] Furthermore, the wavelength of the light is 250-800 nm, preferably 390-420 nm, more preferably 415-420 nm, and even more preferably 415 nm.

[0021] Furthermore, the light originates from LEDs, mercury lamps (including but not limited to high-pressure mercury lamps, medium-pressure mercury lamps, and low-pressure mercury lamps), ultraviolet lamps, or sunlight.

[0022] Furthermore, the reaction time is 0.5-86 hours, preferably 1-72 hours, and more preferably 4-72 hours. Within this range, the reaction time is specifically controlled according to the actual reaction type, such as denitrifying phosphonylation (16 h), denitrifying hydrogenation (6 h), denitrifying deuteration (6 h), denitrifying chlorination (16 h), denitrifying bromination (16 h), and denitrifying carbonization (48 h).

[0023] Furthermore, the reactors used in the reaction include, but are not limited to, glass tubes, Schlenk flasks, (photo)microfluidic reactors, and flat-plate reactors.

[0024] Furthermore, the method also includes the steps of evaporating the reaction solvent to dryness after the reaction, and purifying the residue by silica gel column chromatography.

[0025] In a second aspect, the present invention provides compounds prepared by the method described in the first aspect above.

[0026] It can be understood that the compound is the compound with the structure shown in Formula II above.

[0027] The beneficial effects of this invention are as follows: Compared with existing technologies, the method provided by this invention creatively promotes the functional group transformation of nitro groups in nitro heteroaromatic compounds through photocatalysis, including phosphonylation, hydrogenation, deuteration, halogenation, and carbon-carbon bond construction reactions. The conditions are mild and no external catalyst is required, and the products are easy to separate. This makes the synthesis of the corresponding aromatic compounds simple, low-cost, highly efficient, and less environmentally polluting, achieving more ideal results. In addition, the method provided by this invention is applicable to many biologically active molecules and can be used for the synthesis and modification of drug molecules. It also provides an effective way for hydrogen isotope labeling on the aromatic rings of aromatic compounds. Attached Figure Description

[0028] The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0029] Figure 1 The hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown.

[0030] Figure 2 The hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 11 is shown.

[0031] Figure 3 The hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 15 is shown.

[0032] Figure 4 The hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 22 is shown.

[0033] Figure 5 The hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 24 is shown.

[0034] Figure 6 The hydrogen nuclear magnetic resonance spectrum of the product obtained in Example 25 is shown. Detailed Implementation

[0035] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments and accompanying drawings, further explains the invention. Similar components in the drawings are indicated by the same reference numerals. Those skilled in the art should understand that the specific description below is illustrative rather than restrictive and should not be construed as limiting the scope of protection of the present invention.

[0036] The following are specific examples when the second monomer is a trialkoxyphosphite: An exemplary reaction formula is:

[0037] Example 1 The synthesis of methyl 5-(diisopropoxyphosphoryl)furan-2-carboxylate (1a) is shown in the following structural formula:

[0038] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.2 mmol of methyl 5-nitrofuran-2-carboxylate, 3 mL of ultra-dry isopropanol, and 0.4 mmol of triisopropyl phosphite were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 16 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography was performed (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 1:1, R... f =0.4) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 1:1) to obtain 51.6 mg of product, with a yield of 89%.

[0039] Its main physicochemical properties are as follows: Yellow solid; 1 H NMR (400 MHz, CDCl3): d 7.21 – 7.17 (m, 1H), 7.16 – 7.13 (m, 1 H), 4.82 – 4.71 (m, 2 H), 3.91 (s, 3 H), 1.39 (d, J = 6.2 Hz, 6 H), 1.29(d, J = 6.2 Hz, 6 H); 13 C NMR (101 MHz, CDCl3): d 158.6 (d, J = 1.8 Hz), 149.5 (d, J = 224.6 Hz), 148.3, 122.5 (d, J = 23.9 Hz), 117.5 (d, J = 10.6 Hz), 72.4 (d, J = 5.7 Hz), 52.2, 24.0 (d, J = 4.3 Hz), 23.7 (d, J = 4.8 Hz); 31 P NMR (162 MHz, CDCl3): d -0.36; HRMS (ESI): calcd for C 12 H 19 NaO6P + [M+Na] +: 313.0811, found:313.0804. Example 2 The synthesis of (5-(hydroxymethyl)furan-2-yl)phosphonate diisopropyl ester (1b) is shown in the following structural formula:

[0040] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.2 mmol of (5-nitrofuran-2-yl)methanol, 3 mL of ultra-dry isopropanol, and 0.4 mmol of triisopropyl phosphite were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 16 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 1:1, R...) was performed. f =0.4) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 1:1) to obtain 34.9 mg of product, with a yield of 67%.

[0041] Its main physicochemical properties are as follows: Yellow solid; 1 H NMR (400 MHz, CDCl3): d 7.07 – 6.99 (m, 1 H), 6.40 – 6.34 (m, 1 H), 4.74 – 4.62 (m, 4 H), 3.08 (s, 1 H), 1.36 (d, J = 6.2 Hz, 6 H), 1.26(d, J = 6.2 Hz, 6 H); 13 C NMR (101 MHz, CDCl3): d 160.1 (d, J = 10.0 Hz), 144.4(d, J = 244.0 Hz), 123.1 (d, J = 24.8 Hz), 108.0 (d, J = 10.9 Hz), 71.8 (d, J =5.4 Hz), 57.4, 24.0 (d, J = 4.1 Hz), 23.7 (d, J = 4.9 Hz); 31P NMR (162 MHz, CDCl3): d 2.17; HRMS (ESI): calcd for C 11 H 19 NaO5P + [M+Na] + : 285.0862, found:285.0862. Example 3 The synthesis of (5-cyanofuran-2-yl)phosphonate diisopropyl ester (1c) is shown in the following structural formula:

[0042] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.2 mmol of 5-nitrofuran-2-onitrile, 3 mL of ultra-dry isopropanol, and 0.4 mmol of triisopropyl phosphite were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 16 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. The reaction was then analyzed by thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 1:3, R...). f =0.3) Monitor the reaction progress. After the reaction is completed, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 1:1) to obtain 37.0 mg of product, yield 72%.

[0043] Its main physicochemical properties are as follows: Yellow oil; 1 H NMR (400 MHz, CDCl3): d 7.15 – 7.14 (m, 2 H), 4.83 – 4.72 (m, 2 H), 1.40 (d, J = 6.2 Hz, 6 H), 1.30 (d, J = 6.2 Hz, 6 H); 13 C NMR (101 MHz, CDCl3): d 151.5 (d, J = 236.0 Hz), 129.9 (d, J = 13.3 Hz), 121.8 (d, J = 4.4 Hz), 121.6 (d, J = 17.2 Hz), 110.5 (d, J= 2.0 Hz), 72.9 (d, J = 5.8 Hz), 24.0 (d, J =4.4 Hz), 23.7 (d, J = 4.8 Hz); 31 P NMR (162 MHz, CDCl3): d - 2.12; HRMS (ESI): calcd for C 11 H 16 NNaO4P + [M+Na] + : 280.0709, found: 280.0711. Example 4 The synthesis of (3-bromothiophene-2-yl)phosphonate diisopropyl ester (1d) is shown in the following structural formula:

[0044] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.2 mmol of 3-bromo-2-nitrofuran, 3 mL of ultra-dry isopropanol, and 0.4 mmol of triisopropyl phosphite were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 16 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. The reaction was then analyzed by thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 1:1, R...). f =0.4) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 1:1) to obtain 53.7 mg of product, with a yield of 82%.

[0045] Its main physicochemical properties are as follows: White solid; 1 H NMR (400 MHz, CDCl3) d 7.56 (t, J = 5.0 Hz, 1 H), 7.13 (t, J = 3.8 Hz, 1 H), 4.81 – 4.68 (m, J = 6.4 Hz, 2 H), 1.41 (d, J = 6.0 Hz, 6 H), 1.30 (d, J = 6.1 Hz, 6 H); 13C NMR (100 MHz, CDCl3) d 133.0 (d, J = 14.8 Hz), 132.8 (d, J = 7.3 Hz), 126.2 (d, J = 212.7 Hz), 117.3 (d, J = 7.0 Hz), 72.0 (d, J = 5.4 Hz), 24.0 (d, J = 4.1 Hz), 23.6 (d, J = 5.1 Hz); 31 P NMR (162 MHz, CDCl3): d 5.74; HRMS (ESI) Calcd for C 10 H 17 BrO3PS + (M+H) + :326.9814, Found: 326.9811. Example 5 The synthesis of methyl 5-chloro-4-(diisopropoxyphosphoryl)thiophene-2-carboxylic acid (1e) is shown in the following structural formula:

[0046] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.1 mmol of methyl 5-chloro-4-nitrothiophene-2-carboxylate, 3 mL of ultra-dry isopropanol, and 0.4 mmol of triisopropyl phosphite were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 16 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. The reaction was then analyzed by thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 1:1, R... f =0.4) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 1:1) to obtain 18.2 mg of product, yield 54%.

[0047] Its main physicochemical properties are as follows: Yellow oil; 1 H NMR (400 MHz, CDCl3) d 8.27 (d, J= 3.9 Hz, 1 H), 5.08 – 4.84(m, J = 6.2 Hz, 2 H), 3.96 (s, 3 H), 1.43 (d, J = 6.2 Hz, 6 H), 1.35 (d, J = 6.2Hz, 6 H); 13 C NMR (100 MHz, CDCl3) d 160.4 (d, J = 2.7 Hz), 148.7 (d, J = 3.5 Hz), 137.7 (d, J = 8.0 Hz), 137.5 (d, J = 202.4 Hz), 129.7 (d, J = 10.1 Hz), 73.7 (d, J = 6.3 Hz), 53.1, 24.1 (d, J = 4.0 Hz), 23.7 (d, J = 5.4 Hz); 31 P NMR (162 MHz, CDCl3): d 0.51. Example 6 The synthesis of (5-(pyridin-3-yl)thiophen-2-yl)phosphonate diisopropyl ester (1f) is shown in the following structural formula:

[0048] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.2 mmol of 3-(5-nitrothiophene-2-yl)pyridine, 3 mL of ultra-dry isopropanol, and 0.4 mmol of triisopropyl phosphite were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 16 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. The reaction was then analyzed by thin-layer chromatography (developing solvent: ethyl acetate, R...). f =0.3) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: ethyl acetate) to obtain 63.9 mg of product, with a yield of 83%.

[0049] Its main physicochemical properties are as follows: Yellow oil; 1H NMR (400 MHz, CDCl3) d 8.87 (s, 1H), 8.54 (d, J = 4.5 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1 H), 7.60 (dd, J = 8.3, 3.7 Hz, 1 H), 7.35 (t, J = 3.5Hz, 1 H), 7.32 (dd, J = 7.9, 4.9 Hz, 1 H), 4.83 – 4.59 (m, 2 H), 1.36 (d, J =6.2 Hz, 6 H), 1.27 (d, J = 6.2 Hz, 6 H); 13 C NMR (100 MHz, CDCl3) d 149.4, 147.8(d, J = 7.6 Hz), 147.0, 137.1 (d, J = 11.2 Hz), 133.3, 130.2 (d, J = 209.8 Hz), 129.3 (d, J = 1.6 Hz), 124.8 (d, J = 17.0 Hz), 123.7, 71.6 (d, J = 5.5 Hz), 23.9 (dd, J = 24.1, 4.5 Hz); 31 P NMR (162 MHz, CDCl3): d 8.48; HRMS (ESI) Calcd for C 15 H 21 NO3PS + (M+H) + : 326.0975, Found: 326.0972. Example 7 5-(diisopropoxyphosphoryl)-1 H The synthesis of methyl pyrrole-2-carboxylic acid (1g), with the following structural formula:

[0050] The specific preparation method includes the following steps: Add 0.1 mmol of 5-nitro-1 to a 4 mL Schlenk tube that has been dried in an oven. H Methyl pyrrole-2-carboxylate, 3 mL of ultra-dry isopropanol, and 0.2 mmol of triisopropyl phosphite were degassed and the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 30 h at approximately 30°C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate = 1:1, R...) was then performed. f =0.3) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: ethyl acetate) to obtain 21.8 mg of product, with a yield of 75%.

[0051] Its main physicochemical properties are as follows: Yellow oil; 1 H NMR (400 MHz, CDCl3) d 8.87 (s, 1 H), 8.54 (d, J = 4.5 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1 H), 7.60 (dd, J = 8.3, 3.7 Hz, 1 H), 7.35 (t, J = 3.5Hz, 1 H), 7.32 (dd, J = 7.9, 4.9 Hz, 1 H), 4.83 – 4.59 (m, 2 H), 1.36 (d, J =6.2 Hz, 6 H), 1.27 (d, J = 6.2 Hz, 6 H); 13 C NMR (100 MHz, CDCl3) d 149.4, 147.8(d, J = 7.6 Hz), 147.0, 137.1 (d, J = 11.2 Hz), 133.3, 130.2 (d, J = 209.8 Hz), 129.3 (d, J = 1.6 Hz), 124.8 (d, J = 17.0 Hz), 123.7, 71.6 (d, J = 5.5 Hz), 23.9 (dd, J = 24.1, 4.5 Hz); 31P NMR (162 MHz, CDCl3): d 8.48; HRMS (ESI) Calcd for C 12 H 21 NO5P + (M+H) + Found: 290.1152, Found: 290.1151. Example 8 5-(bis(benzyloxy)phosphoryl)-1-methyl-1 H The synthesis of methyl pyrrole-2-carboxylic acid (1h) is shown in the following structural formula:

[0052] The specific preparation method includes the following steps: Add 0.1 mmol of 5-nitro-1 to a 4 mL Schlenk tube that has been dried in an oven. H Methyl pyrrole-2-carboxylate, 3 mL of ultra-dry isopropanol, and 0.2 mmol of tribenzyl phosphite were degassed and the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 24 h at approximately 30°C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate = 1:1, R...) was then performed. f =0.5) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: ethyl acetate) to obtain 32.0 mg of product, with a yield of 80%.

[0053] Its main physicochemical properties are as follows: Yellow oil; 1 H NMR (400 MHz, CDCl3) d 7.35 – 7.28 (m, 10 H), 6.88 (t, J = 4.3Hz, 1 H), 6.80 – 6.72 (m, 1 H), 5.08 (dd, J = 8.4, 4.3 Hz, 4 H), 3.94 (s, 3H), 3.82 (s, 3 H); 13 C NMR (100 MHz, CDCl3) d 161.1 (d, J = 2.9 Hz), 135.6 (d, J =6.7 Hz), 128.5, 128.5, 128.0, 127.9, 68.1 (d,J = 5.3 Hz), 51.5, 35.2 (d, J =1.2 Hz); 31 P NMR (162 MHz, CDCl3): d 9.08; HRMS (ESI) Calcd for C 12 H 21 NO5P + (M+H) + :400.1309, Found: 400.1306. The following are specific examples when the second monomer is 1,3-dimethylimidazol-2-methyleneborane or 1,3-dimethylimidazol-2-methylenedeuteratedborane: An exemplary reaction formula is:

[0054] Example 9 Thiophene-2-carboxylic acid-( S The synthesis of 3,7-dimethylhept-6-en-1-yl ester (2a) is described below, with the following structural formula:

[0055] The specific preparation method includes the following steps: Add 0.1 mmol of 5-nitrothiophene-2-carboxylic acid to a 4 mL Schlenk tube that has been dried in an oven. S 3,7-Dimethylhept-6-en-1-yl ester, 2 mL of ultra-dry acetonitrile, and 0.2 mmol of 1,3-dimethylimidazolium-2-methyleneborane were degassed and the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 3 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: dichloromethane, R...) was then performed. f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: dichloromethane) to obtain 17.6 mg of product, with a yield of 66%.

[0056] Its main physicochemical properties are as follows: Colorless oil; 1 H NMR (400 MHz, CDCl3): d 7.79 (s, 1 H), 7.54 (d, J = 4.7 Hz, 1H), 7.09 (t, J= 4.1 Hz, 1 H), 5.10 (t, J = 6.0 Hz, 1 H), 4.41 – 4.27 (m, 2 H), 2.09 – 1.92 (m, 2 H), 1.86 – 1.74 (m, 1 H), 1.73 – 1.51 (m, 8 H), 1.47 – 1.35(m, 1 H), 1.30 – 1.18 (m, 1 H), 0.96 (d, J = 6.3 Hz, 3 H); 13 C NMR (101 MHz, CDCl3): d 162.3, 134.1, 133.2, 132.1, 131.4, 127.6, 124.5, 63.7, 36.9, 35.4,29.5, 25.7, 25.4, 19.5, 17.6; HRMS (ESI): calcd for C 15 H 23 O2S + [M+H] + : 267.1413,found: 267.1413. Example 10 The synthesis of 3-thiophene-2-ylpyridine (2b) is shown in the following structural formula:

[0057] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.1 mmol of 3-(5-nitrothiophene-2-yl)pyridine, 2 mL of ultra-dry acetonitrile, and 0.2 mmol of 1,3-dimethylimidazolium-2-methyleneborane were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 3 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: ethyl acetate, R...) was then performed. f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: ethyl acetate) to obtain 14.3 mg of product, with a yield of 89%.

[0058] Its main physicochemical properties are as follows: Colorless oil; 1 H NMR (400 MHz, CDCl3): d 8.89 (s, 1 H), 8.52 (d,J = 3.8 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1 H), 7.36 (d, J = 3.6 Hz, 2 H), 7.33 – 7.28 (m, 1 H), 7.12 (t, J = 3.3 Hz, 1 H); 13 C NMR (101 MHz, CDCl3): d 148.4, 147.0, 140.4,133.0, 130.4, 128.2, 126.0, 124.2, 123.6; HRMS (ESI): calcd for C9H8NS + [M+H] + :162.0372, found: 162.0370. Example 11 The synthesis of 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionic acid-furan-2-ylmethyl ester (2c) is shown in the following structural formula:

[0059] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.1 mmol of 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionic acid-5-nitrofuran-2-ylmethyl ester, 2 mL of ultra-dry acetonitrile, and 0.2 mmol of 1,3-dimethylimidazolium-2-methyleneborane were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. Under an argon atmosphere, the reaction system was irradiated with a 415-420 nm LED light source at approximately 30 °C (maintained by two cooling fans) for 2 h. The reaction was then analyzed by thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate = 1:1, R...). f =0.4) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate = 1:1) to obtain 29.4 mg of product, with a yield of 74%.

[0060] Its main physicochemical properties are as follows: Yellow solid; 1 H NMR (400 MHz, CDCl3): d 7.70 (d, J = 8.4 Hz, 2 H), 7.65 (d, J = 8.8 Hz, 2 H), 7.45 (d,J = 8.4 Hz, 2 H), 7.37 – 7.35 (m, 1 H), 6.77 (d, J =8.8 Hz, 2 H), 6.39 (d, J = 3.2 Hz, 1 H), 6.36 – 6.31 (m, 1 H), 5.18 (s, 2 H), 1.66 (s, 6 H); 13 C NMR (101 MHz, CDCl3): d HRMS (ESI): calcd for C 22 H 20 ClO5 + [M+H] + : 399.0994, found: 399.0995. Example 12 The synthesis of 4-(furan-2-yl)quinoline (2d) is shown in the following structural formula:

[0061] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.1 mmol of 4-(5-nitrofuran-2-yl)quinoline, 2 mL of ultra-dry acetonitrile, and 0.2 mmol of 1,3-dimethylimidazolium-2-methyleneborane were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 6 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: ethyl acetate, R...) was then performed. f =0.4) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: ethyl acetate) to obtain 11.0 mg of product, with a yield of 56%.

[0062] Its main physicochemical properties are as follows: Yellow solid; 1 H NMR (400 MHz, CDCl3): d 8.93 (d, J = 4.6 Hz, 1 H), 8.51 (d,J = 8.5 Hz, 1 H), 8.16 (d, J = 8.4 Hz, 1 H), 7.75 (t, J = 7.6 Hz, 1 H), 7.69 (s,1 H), 7.65 – 7.58 (m, 2 H), 6.99 (d, J = 3.4 Hz, 1 H), 6.64 (dd, J = 3.0, 1.8Hz, 1 H); 13 C NMR (101 MHz, CDCl3): d 151.0, 149.9, 149.0, 144.0, 135.7, 130.1,129.4, 127.0, 125.4, 124.4, 118.5, 112.2, 112.0; HRMS (ESI): calcd forC 13 H 10 NO + [M+H] + : 196.0757, found: 196.0759. Example 13 2-(2-fluoro-[1,1'-biphenyl]-4-yl)-1-(1 H The synthesis of (-indol-1-yl)prop-1-one (2e) is shown in the following structural formula:

[0063] The specific preparation method includes the following steps: Add 0.1 mmol of 2-(2-fluoro-1,1'-biphenyl-4-yl)-1-(3-nitro-1-yl) to a 4 mL Schlenk tube that has been dried in an oven. H (-indol-1-yl)prop-1-one, 2 mL ultra-dry acetonitrile, and 0.2 mmol 1,3-dimethylimidazolium-2-methyleneborane were degassed and the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 3 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: dichloromethane, R...) was then performed. f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: dichloromethane) to obtain 15.8 mg of product, with a yield of 46%.

[0064] Its main physicochemical properties are as follows: Yellow solid;1 H NMR (400 MHz, CD3CN): d 8.47 (d, J = 8.2 Hz, 1 H), 7.67 (d, J = 3.8 Hz, 1 H), 7.54 (d, J = 8.0 Hz, 1 H), 7.50 – 7.46 (m, 2 H), 7.44 – 7.38 (m, 3 H), 7.38 – 7.30 (m, 2 H), 7.27 – 7.22 (m, 3 H), 6.61 (d, J = 3.8 Hz, 1H), 4.67 (q, J = 6.8 Hz, 1 H), 1.59 (d, J = 6.8 Hz, 3 H); 13 C NMR (101 MHz, CD3CN): d 173.3, 160.6 (d, J = 246.9 Hz), 143.8 (d, J = 7.8 Hz), 136.7, 136.0 (d, J = 1.0 Hz), 132.3 (d, J = 3.9 Hz), 131.4, 129.8 (d, J = 2.9 Hz), 129.5,128.8, 128.6 (d, J = 13.6 Hz), 126.7, 125.9, 124.7, 124.6 (d, J = 3.3 Hz),121.8, 117.3, 116.0 (d, J = 23.9 Hz), 109.8, 45.7, 20.0; 19 F NMR (377 MHz, CD3CN): d -118.67. Example 14 The synthesis of 3,7-dimethyl octyl 5-deuterated furan-2-carboxylic acid (2f) is shown in the following structural formula:

[0065] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.1 mmol of 3,7-dimethyl octyl 5-nitrofuran-2-carboxylic acid, 2 mL of ultra-dry acetonitrile, and 0.2 mmol of 1,3-dimethylimidazolium-2-methylene deuterated borane were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 4 h under an argon atmosphere using a 415-420 nm LED light source at approximately 30 °C (maintained by two cooling fans). The reaction was then analyzed by thin-layer chromatography (developing solvent: dichloromethane, R...). f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: dichloromethane) to obtain 18.5 mg of product, with a yield of 73% and a deuteration rate of 97%.

[0066] Its main physicochemical properties are as follows: Colorless oily substance; 1 H NMR (400 MHz, CDCl3): d 7.16 (d, J = 3.5 Hz, 1 H), 6.50(d, J = 3.4 Hz, 1 H), 4.40 – 4.30 (m, 2 H), 1.84 – 1.74 (m, 1 H), 1.63 – 1.48(m, 3 H), 1.15 (t, J = 7.0 Hz, 3 H), 0.94 (d, J = 6.3 Hz, 3 H), 0.86 (d, J = 6.6Hz, 6 H); 13 C NMR (101 MHz, CDCl3): d 158.9, 145.9 (t, J C-D = 31.1 Hz), 144.9,117.7, 111.6, 63.6, 39.2, 37.1, 35.5, 29.9, 28.0, 24.6, 22.7, 22.6, 19.6;HRMS (ESI): calcd for C 15 H 23 DNaO3 + [M+Na] + : 276.1680, found: 276.1681. Example 15 The synthesis of methyl 6-(3-(adamantane-1-yl)-4-methoxyphenyl)-2-naphthoic acid (5-deuterated furan-2-yl) ester (2g) is shown in the following structural formula:

[0067] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.05 mmol of 6-(3-(adamantane-1-yl)-4-methoxyphenyl)-2-naphthoic acid (5-nitrofuran-2-yl) methyl ester, 2 mL of ultra-dry acetonitrile, and 0.2 mmol of 1,3-dimethylimidazolium-2-methylene deuterated borane were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 20 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. The reaction was then analyzed by thin-layer chromatography (developing solvent: dichloromethane, R...). f =0.8) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: dichloromethane) to obtain 17.7 mg of product, with a yield of 72% and a deuteration rate of 94%.

[0068] Its main physicochemical properties are as follows: White solid; 1 H NMR (400 MHz, CDCl3): d 8.61 (s, 1 H), 8.07 (d, J = 8.7 Hz,1 H), 8.02 – 7.93 (m, 2 H), 7.90 (d, J = 8.6 Hz, 1 H), 7.78 (d, J = 8.6 Hz, 1H), 7.61 – 7.57 (m, 1 H), 7.56 – 7.50 (m, 1 H), 6.99 (d, J = 8.5 Hz, 1 H),6.56 – 6.51 (m, 1 H), 6.43 – 6.38 (m, 1 H), 5.38 (s, 2 H), 3.90 (s, 3 H),2.18 (s, 6 H), 2.10 (s, 3 H), 1.80 (s, 6 H); 13 C NMR (101 MHz, CDCl3): d166.5,158.9, 149.6, 141.5, 139.0, 136.1, 132.5, 131.2, 131.1, 129.8, 128.2, 126.6,126.5, 126.0, 125.74, 125.68, 124.7, 112.1, 110.9, 110.5, 58.6, 55.2, 40.6,37.2, 37.1, 29.1; HRMS (ESI): calcd for C 33 H 32 DO4 + [M+H] + : 494.2436, found:494.2436. Example 16 The synthesis of 4-(5-deuterated furan-2-yl)quinoline (2h) is shown in the following structural formula:

[0069] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.1 mmol of 4-(5-nitrofuran-2-yl)quinoline, 2 mL of ultra-dry acetonitrile, and 0.2 mmol of 1,3-dimethylimidazolium-2-methylenedeuterated borane were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. Under an argon atmosphere, the reaction system was irradiated with a 415-420 nm LED light source at approximately 30 °C (maintained by two cooling fans) for 4 h. The reaction was then analyzed by thin-layer chromatography (developing solvent: dichloromethane / methanol (volume ratio) = 30:1, R... f =0.5) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: chloromethane / methanol (volume ratio) = 30:1) to obtain 15.2 mg of product, with a yield of 77% and a deuteration rate of 94%.

[0070] Its main physicochemical properties are as follows: Yellow solid; 1 H NMR (400 MHz, CDCl3): d 8.93 (d, J = 4.6 Hz, 1 H), 8.51 (d, J = 8.5 Hz, 1 H), 8.17 (d, J = 8.5 Hz, 1 H), 7.80 – 7.71 (m, 1 H), 7.67 – 7.58 (m, 2 H), 7.00 (d, J= 3.4 Hz, 1 H), 6.64 (d, J = 3.4 Hz, 1 H); 13 C NMR (101 MHz, CDCl3): d 151.0, 149.9, 149.0, 135.9, 130.1, 129.5, 127.1, 125.5, 124.5,118.6, 112.3, 111.8; HRMS (ESI): calcd for C 13 H9DNO + [M+H] + : 197.0820, found:197.0820. Example 17 The synthesis of 4-(5-deuterated furan-2-yl)quinoline (2i) is shown in the following structural formula:

[0071] The specific preparation method includes the following steps: In a 4 mL Schlenk tube that had been dried in an oven, 0.1 mmol of N-(2-morpholinoethyl)-4-(5-nitrofuran-2-yl)benzamide, 2 mL of ultra-dry acetonitrile, and 0.2 mmol of 1,3-dimethylimidazolium-2-methylenedeuterated borane were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 8 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: dichloromethane / methanol (v / v) = 10:1, R...) was performed. f =0.5) Monitor the reaction progress. After the reaction is completed, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: chloromethane / methanol (volume ratio) = 10:1) to obtain 25.9 mg of product, with a yield of 86% and a deuteration rate of 91%.

[0072] Its main physicochemical properties are as follows: Yellow solid; 1 H NMR (400 MHz, CDCl3): d 7.84 – 7.77 (m, 2 H), 7.77 – 7.70 (m, 2 H), 6.82 (s, 1 H), 6.75 (d, J = 3.4 Hz, 1 H), 6.50 (d, J = 3.4 Hz, 1 H), 3.74 (t, J= 4.7 Hz, 4 H), 3.57 (q, J = 5.7 Hz, 2 H), 2.62 (t, J = 6.0 Hz, 2 H), 2.52 (d, J = 8.1 Hz, 4 H); 13 C NMR (101 MHz, CDCl3): d 166.9, 152.9, 142.7 (t, J C-D = 30.7 Hz), 133.6, 132.9, 127.4, 123.7, 112.0, 111.8, 106.7, 67.0, 56.9,53.4, 36.0; HRMS (ESI): calcd for C 17 H 20 DN2O3 + [M+H] + 302.1609, found: 302.1605 Example 18 ((3 aR 4 S 5 R 6 aS )-5-benzoyloxy-2-oxohexahydro-2 H -Cyclopenta[ b The synthesis of furan-4-yl)methyl-5-deuterated thiophene-2-carboxylate (2j) is shown in the following structural formula:

[0073] The specific preparation method includes the following steps: Add (3) to a 4 mL Schlenk tube that has been dried in an oven. aR 4 S 5 R 6 aS )-5-benzoyloxy-2-oxohexahydro-2 H -Cyclopenta[ b Furan-4-yl)methyl-5-nitrothiophene-2-carboxylate, 2 mL of ultra-dry acetonitrile, and 0.2 mmol of 1,3-dimethylimidazolium-2-methylene deuterated borane were degassed and the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 8 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 1:2, R...) was performed. f=0.7) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 1:2) to obtain 31.7 mg of product, with a yield of 82% and a deuteration rate of 99%.

[0074] Its main physicochemical properties are as follows: Colorless oily substance; 1 H NMR (400 MHz, CDCl3): d 8.00 (d, J = 7.7 Hz, 1H), 7.81 (d, J = 3.7 Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 7.11 (d, J = 3.8 Hz, 1H), 5.51 – 5.38 (m, 1H), 5.14 (t, J = 6.3 Hz, 1H), 4.47 – 4.33 (m,2H), 3.04 – 2.84 (m, 2H), 2.72 – 2.53 (m, 3H), 2.50 – 2.35 (m, 1H); 13 C NMR (101 MHz, CDCl3): d HRMS (ESI): calcd forC 20 H 17 DNaO6S + [M+Na] + : 410.0779, found: 410.0778. The following are specific examples when the second monomer is N-chloro / bromosuccinimide.

[0075] An exemplary reaction formula is:

[0076] Example 19 The synthesis of 5-chlorothiophene-2-carboxynitrile (3a) is shown in the following structural formula:

[0077] 0.1 mmol of 5-nitrothiophene-2-carboxynitrile, 2 mL of ultra-dry acetonitrile, and 0.18 mmol of N-chlorosuccinimide were added sequentially to a 4 mL Schlenk tube that had been dried in an oven. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 20 h at approximately 30 °C using a 415-420 nm LED light source under an argon atmosphere (temperature maintained by two cooling fans). The reaction was then analyzed by thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 5:1, R...). f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 5:1) to obtain 11.5 mg of product, yield 80%.

[0078] Its main physicochemical properties are as follows: Yellow oil; 1 H NMR (400 MHz, CDCl3): d 7.44 (d, J = 4.1 Hz, 1H), 6.97 (d, J =4.0 Hz, 1H). Example 20 The synthesis of methyl 4-bromo-5-chlorothiophene-2-carboxylic acid (3b) is shown in the following structural formula:

[0079] 0.2 mmol of 4-bromo-5-nitrothiophene-2-carboxynitrile, 3 mL of ultra-dry acetonitrile, and 0.36 mmol of N-chlorosuccinimide were added sequentially to a 4 mL Schlenk tube that had been dried in an oven. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 20 h at approximately 30 °C using a 415-420 nm LED light source under an argon atmosphere (temperature maintained by two cooling fans). Thin-layer chromatography was performed (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 5:1, R... f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 5:1) to obtain 45.6 mg of product, with a yield of 89%.

[0080] Its main physicochemical properties are as follows: White solid; 1 H NMR (400 MHz, CDCl3): d 7.56 (s, 1 H), 3.89 (s, 3 H); 13CNMR (101 MHz, CDCl3): d 160.8, 132.5, 131.7, 129.6, 125.1, 52.6; HRMS (EI):calcd for C6H4BrClO2S ·+ [M] ·+ : 255.8778, found: 255.8772. Example 21 The synthesis of methyl 4,5-dichlorothiophene-2-carboxylate (3c) is shown in the following structural formula:

[0081] In a 4 mL Schlenk tube that had been dried in an oven, 0.2 mmol of methyl 5-chloro-4-nitrothiophene-2-carboxylate, 3 mL of ultra-dry acetonitrile, and 0.36 mmol of N-chlorosuccinimide were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 20 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography was performed (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 5:1, R... f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 5:1) to obtain 35.0 mg of product, yield 83%.

[0082] Its main physicochemical properties are as follows: White solid; 1 H NMR (400 MHz, CDCl3): d 7.60 (s, 1 H), 3.92 (s, 3 H); 13 CNMR (101 MHz, CDCl3): d 160.9, 132.6, 131.7, 129.6, 125.1, 52.6; HRMS (EI):calcd for C6H4Cl2O2S ·+ [M] ·+ : 209.9304, found: 209.9302. Example 22 (1 R ,2 R 4 R The synthesis of 1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl-5-chlorothiophene-2-carboxylic acid ester (3d) was carried out, and its structural formula is as follows:

[0083] Add 0.1 mmol (1) to a 4 mL Schlenk tube that has been dried in an oven. R ,2 R 4 R 1,7,7-Trimethylbicyclo[2.2.1]heptane-2-yl-5-nitrothiophene-2-carboxylic acid ester, 6 mL of ultra-dry acetonitrile and 0.36 mmol of N-chlorosuccinimide were degassed and the reaction tube was sealed with a rubber stopper and sealing film; the reaction system was irradiated for 20 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere; thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 5:1, R f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 5:1) to obtain 19.9 mg of product, yield 66%.

[0084] Its main physicochemical properties are as follows: Yellow oil; 1 H NMR (400 MHz, CDCl3): d 7.59 (s, 1 H), 6.94 (s, 1 H), 5.06 (d, J = 9.5 Hz, 1 H), 2.43 (t, J = 11.8 Hz, 1 H), 2.02 (t, J = 12.1 Hz, 1 H), 1.79 (t, J = 12.8 Hz, 1 H), 1.73 (s, 1 H), 1.38 (d, J = 12.6 Hz, 1 H), 1.33 –1.26 (m, 1 H), 0.94 (s, 3 H), 0.90 (s, 3 H), 0.89 (s, 3 H); 13 C NMR (101 MHz, CDCl3): d 161.5, 137.0, 132.5, 127.2, 81.2, 49.1, 47.9, 44.9, 36.7, 28.0, 27.3, 19.7, 18.9, 13.5. Example 23 The synthesis of (5-chlorofuran-2-carbonyl)tryptophan methyl ester (3e) is shown in the following structural formula:

[0085] 0.2 mmol (5-nitrofuran-2-carbonyl)tryptophan methyl ester, 3 mL ultra-dry acetonitrile, and 0.095 mmol N-chlorosuccinimide were added sequentially to a 4 mL Schlenk tube that had been dried in an oven. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 20 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 1:1, R...) was performed. f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 1:1) to obtain 33.5 mg of product, yield 51%.

[0086] Its main physicochemical properties are as follows: Yellow solid; 1 H NMR (400 MHz, CDCl3): d 8.40 (s, 1 H), 7.47 (d, J = 7.8 Hz, 1 H), 7.29 (d, J = 3.8 Hz, 1 H), 7.16 (d, J = 65.4 Hz, 5 H), 5.03 (dt, J = 7.9,5.8 Hz, 1 H), 3.74 (s, 3 H), 3.45 – 3.33 (m, 2 H); 13 C NMR (101 MHz, CDCl3): d 171.2, 156.0, 151.3, 147.3, 134.4, 127.3, 122.8, 122.2, 120.6, 117.8, 116.2, 112.1, 110.7, 105.9, 52.8, 52.7, 26.5. Example 24 The synthesis of methyl 4,5-dibromo-thiophene-2-carboxylic acid (3f) is shown in the following structural formula:

[0087] In a 4 mL Schlenk tube that had been dried in an oven, 0.2 mmol of 4-bromo-5-nitrothiophene-2-carboxynitrile, 3 mL of ultra-dry acetonitrile, and 0.2 mmol of N-bromosuccinimide were added sequentially. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 12 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. Thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate (volume ratio) = 5:1, R...) was performed. f =0.6) Monitor the reaction progress. After the reaction is complete, remove the solvent under reduced pressure. The remaining residue is purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate (volume ratio) = 5:1) to obtain 45.0 mg of product, yield 75%.

[0088] Its main physicochemical properties are as follows: White solid; 1 H NMR (400 MHz, CDCl3): d 7.58 (s, 1 H), 3.89 (s, 3 H); 13 CNMR (101 MHz, CDCl3): d 160.7, 135.4, 134.1, 119.1, 114.9, 52.6. The following are specific examples when the fourth monomer is tert-butane iodide.

[0089] An exemplary reaction formula is:

[0090] Example 25 The synthesis of methyl 5-(2-methylprop-1-en-1-yl)thiophene-2-carboxylic acid (4a) is shown in the following structural formula:

[0091] 0.2 mmol of methyl 5-nitrothiophene-2-carboxylate, 3 mL of ultra-dry acetonitrile, and 4 mmol of tert-butane iodide were added sequentially to a 4 mL Schlenk tube that had been dried in an oven. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated for 48 h at approximately 30 °C (maintained by two cooling fans) using a 415-420 nm LED light source under an argon atmosphere. The reaction progress was monitored by thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate = 10:1, Rf = 0.6). After the reaction was completed, the solvent was removed under reduced pressure, and the remaining residue was purified by silica gel rapid column chromatography (eluent: petroleum ether / ethyl acetate = 10:1) to give 17.7 mg of product, with a yield of 45%.

[0092] Its main physicochemical properties are as follows: White solid; 1 H NMR (400 MHz, CDCl3): d 7.71 (d, J = 3.9 Hz, 1 H), 6.89 (d, J = 3.9 Hz, 1 H), 6.42 (s, 1 H), 3.90 (s, 3 H), 2.05 (s, 3 H), 1.98 (s, 3 H); 13 CNMR (101 MHz, CDCl3): d 162.9, 148.6, 138.8, 133.4, 130.7, 126.3, 118.5, 52.0,27.5, 20.4; HRMS (EI): calcd for C 10 H 12 O2S ·+ [M] ·+ : 196.0553, found: 196.0552. Example 26 This example explores the effects of organic solvents and light on the reaction yield. The specific method is as follows: 2-Nitrothiophene (0.2 mmol), triisopropyl phosphite (1.0–5.0 equiv.), and ultra-dry reaction solvent were added sequentially to a 4 mL Schlenk tube that had been dried in an oven. After degassing, the reaction tube was sealed with a rubber stopper and sealing film. The reaction system was irradiated at the above temperature for 16 h under an argon atmosphere using a 415–420 nm LED light source. The crude reaction mixture was analyzed using dibromomethane (0.2 mmol) as an internal standard. 1 H NMR analysis (400 MHz) was used to determine the yield.

[0093]

[0094] The specific solvent selection, light source selection, and results are shown in Table 1. As can be seen from Table 1, the yield is highest and the effect is best when the organic solvent is isopropanol. Toluene, DMF, dichloromethane, acetone, dimethyl sulfoxide, acetonitrile, ethyl acetate, 1,4-dioxane, ethanol and other organic solvents can all support the reaction, but not as well as isopropanol. The reaction cannot occur under light conditions, whether at room temperature or 60°C.

[0095] Table 1

[0096] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all the implementation methods here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A method for photo-promoted direct denitration of nitroaromatic compounds, characterized in that, The method includes the following steps: The first monomer is selected from nitro-heteroaromatic hydrocarbons with the structure shown in Formula I. I, and The second monomer is selected from phosphonylating agents, hydrogenating agents, deuterating agents, halogenating agents, or carbonizing agents. As raw materials, In an organic solvent, under room temperature and argon protection, light irradiation is used to directly denitrate the nitro aromatic hydrocarbon to generate a compound with the structure shown in Formula II: II in, The FG is selected from H, D, Cl, Br, C or P; X is selected from S, O, NH or NR. 2 ; The R 2 Selected from alkyl, aryl, or heteroaryl groups; The R is selected from alkyl, alkenyl, alkynyl, aryl, heteroaryl, halogen, hydroxyl, amino, alkoxy, ester, amide, or any of the aforementioned alkyl, alkenyl, alkynyl, aryl, or heteroaryl groups in which at least one hydrogen atom is substituted.

2. The method according to claim 1, characterized in that, The phosphonylating agent is selected from trialkoxyphosphite, and its structural formula is shown in Formula III below: III Wherein, the R 1 Selected from C1-C10 alkyl, C5-C10 heteroaryl, and aryl groups.

3. The method according to claim 2, characterized in that, The C5-C10 heteroaryl group is a five-membered heteroaryl or a six-membered heteroaryl.

4. The method according to claim 1, characterized in that, The hydrogenating agent is selected from 1,3-dimethylimidazol-2-methyleneborane; or The deuterating agent is selected from 1,3-dimethylimidazolium-2-methylenedeuteronane; or The carbonizing agent is selected from tert-butane iodo.

5. The method according to claim 1, characterized in that, The halogenating agent is selected from chlorinating agents or brominating agents; Preferably, the chlorinating agent is selected from N-chlorosuccinimide; Preferably, the brominating agent is selected from N-bromosuccinimide.

6. The method according to claim 1, characterized in that, The nitro heteroaromatic hydrocarbon is selected from nitrothiophene, nitrofuran, nitropyrrole, nitrobenzothiophene, nitrobenzofuran, or nitroindole.

7. The method according to claim 1, characterized in that, The second monomer is selected from phosphonylating agents, hydrogenating agents, or deuterating agents, and the molar ratio of the first monomer to the second monomer is 1:2; or The second monomer is a halogenating agent, and the molar ratio of the first monomer to the second monomer is 1:(1-2); or The second monomer is a carbonizing agent, and the molar ratio of the first monomer to the second monomer is 1:(2-5).

8. The method according to claim 1, characterized in that, The organic solvent is selected from isopropanol, acetonitrile, or dichloromethane.

9. The method according to claim 1, characterized in that, The wavelength of the light is 250-800 nm, preferably 390-420 nm, more preferably 415-420 nm; and / or The light comes from an LED, mercury lamp, ultraviolet lamp, or sunlight; and / or The reaction time is 0.5-86 hours, preferably 1-72 hours, and more preferably 4-72 hours.

10. The compound prepared by the method according to any one of claims 1-9.

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