Method for constructing gamma amino acid skeleton by photopromoted CO2 immobilization

Abstract

The invention discloses a reaction composition and a method for constructing a gamma-amino acid skeleton by photopromoted CO2 immobilization. The composition comprises a 1, 1-stilbene compound, an alpha-silicon-based carbazole compound, a photocatalyst, alkali and carbon dioxide. The method comprises the following steps: under visible light irradiation and a carbon dioxide atmosphere, carrying out desiliconization on an alpha-silicon-based carbazole compound to generate alpha-amino carbon free radicals by utilizing a photooxidation reduction catalytic mechanism, and then carrying out addition on a 1, 1-stilbene compound and capturing carbon dioxide, so as to construct a gamma-amino acid skeleton. According to the method, a silicon-based activation strategy is utilized, the use of high temperature, high pressure and a metal catalyst is avoided, the method has the advantages of mild reaction conditions, strong substrate universality, high chemical selectivity and the like, and efficient and green synthesis of the carbazole-containing unnatural amino acid is realized.

Description

Technical Field

[0001] This invention relates to the field of organic chemical synthesis technology, specifically to a method for constructing a γ-amino acid backbone by photo-induced CO2 fixation. Background Technology

[0002] Carbon dioxide (CO2) is one of the major greenhouse gases and also an abundant renewable carbon resource. Currently, catalytic conversion of CO2 mostly employs high-temperature and high-pressure conditions, which are energy-intensive, demanding, and often involve toxic and harmful reagents (such as metal catalysts and strong reducing agents). While existing photocatalytic CO2 conversion methods operate under milder conditions, they generally suffer from low conversion efficiency, poor selectivity, and limited product diversity, particularly in constructing high-value-added chemicals with complex structures (such as amino acid skeletons), which still faces significant challenges (Nat. Synth. 2024, 3, 394.).

[0003] Non-natural amino acid backbone fragments are crucial building blocks in pharmaceuticals, materials, and other fields. Currently, China still relies on imports for non-natural amino acids, primarily due to two reasons: First, domestic technology and production scale lag behind advanced international levels, making it difficult to meet the production demands of domestic anticancer drugs and peptide drugs. Second, the methods for synthesizing non-natural amino acids are very limited. Existing methods mainly include chemical synthesis and biosynthesis. Chemical synthesis is often cumbersome and difficult to control stereoselectivity; biosynthesis is limited by enzyme specificity, restricting the types of non-natural amino acids that can be synthesized. Therefore, this invention develops a synergistic strategy of "photo-oxidation-reduction catalysis—electrophilic addition" (…). Figure 2 This technology enables the green and low-carbon synthesis of non-natural amino acids using carbon dioxide. By cleverly designing the catalytic reaction system and introducing various functional groups and substituents, a series of novel and functionally unique non-natural amino acids can be synthesized. This not only significantly expands the variety of non-natural amino acids, providing more options for subsequent research and applications, but also meets the needs of different fields for non-natural amino acids with special structures, thereby promoting research progress in these fields. Summary of the Invention

[0004] The technical problem solved by this invention is that existing carbon dioxide chemical conversion technologies usually rely on high temperature, high pressure or metal catalysts, which consume a lot of energy; while existing photocatalytic carbon dioxide fixation methods face problems such as harsh reaction conditions, poor substrate compatibility and low conversion efficiency when synthesizing γ-amino acids with carbazole skeletons.

[0005] The technical problem solved by this invention is that existing carbon dioxide chemical conversion technologies usually rely on high temperature, high pressure or metal catalysts, which consume a lot of energy; while existing photocatalytic carbon dioxide fixation methods face problems such as harsh reaction conditions, limited substrate applicability and low conversion efficiency when synthesizing γ-amino acids with carbazole skeletons.

[0006] To address the above problems, the present invention provides the following technical solution:

[0007] In a first aspect, the present invention provides a reaction composition for photo-induced CO2 immobilization to construct a γ-amino acid backbone, employing the following technical solution:

[0008] A photocatalyst-induced CO2 fixation reaction composition for constructing a γ-amino acid backbone, the composition comprising the following components in molar amounts: component A: 1.0 part; component B: 1.2-2.5 parts; photocatalyst: 0.005-0.06 parts; base: 1.5-6.0 parts; and carbon dioxide gas; wherein component A is selected from 1,1-stilbene or 1,1-di(4-methylphenyl)ethylene; and component B is selected from 9-[(trimethylsilyl)methyl]-9H-carbazole, 3,6-di-tert-butyl-9-[(trimethylsilyl)methyl]-9H-carbazole or 3,6-dibromo-9-[(trimethylsilyl)methyl]-9H-carbazole.

[0009] By employing the above technical solution, this invention achieves a mild conversion of the reaction using the electronic effects of α-silicon. The specific mechanism is as follows:

[0010] Electronic activation: The carbon-silicon bond in component B produces a σ-p hyperconjugation effect (i.e., β-silicon-based effect) with the lone pair electrons of the carbazole nitrogen atom, which reduces the oxidation potential of the nitrogen atom, making component B more susceptible to single-electron oxidation under light conditions.

[0011] Free radical generation: Under visible light excitation, component B is oxidized by an excited-state photocatalyst to generate free radical cations, which then undergo desilication reaction under the action of a base, breaking the carbon-silicon bond and generating α-amino carbon free radicals.

[0012] Carbon-carbon bond construction: The generated α-amino carbon radical selectively adds to component A, and the resulting intermediate is reduced and captured by carbon dioxide to form the target γ-amino acid backbone. This process avoids the high energy barrier of directly activating inert CH bonds and achieves metal-free carbon-carbon bond construction.

[0013] Preferably, the photocatalyst is selected from 4CzIPN, 3DPAFIPN, or Rhodamine B. By adopting the above technical solution, the redox potential of the organic photocatalyst matches the substrate energy level of the reaction system, which can effectively drive the electron transfer process under visible light excitation, while avoiding heavy metal residues.

[0014] Preferably, the alkali is selected from cesium carbonate or potassium bicarbonate. By adopting the above technical solution, this type of alkali can assist the desilication process to promote the generation of active free radicals and neutralize the acidic species generated in the reaction, which is beneficial to the formation of carboxylate products.

[0015] Preferably, the composition further comprises a solvent selected from dimethyl sulfoxide or acetonitrile, and the amount of solvent used is such that the concentration of component A in the solvent is 0.05-0.25 mol / L. By adopting the above technical solution, this polar aprotic solvent system can dissolve carbon dioxide and ionic intermediates, and the selected concentration range takes into account both reaction rate and mass transfer efficiency.

[0016] Preferably, component B is prepared by a method comprising the following steps: (1) dissolving a raw material selected from carbazole, 3,6-di-tert-butylcarbazole or 3,6-dibromocarbazole in anhydrous N,N-dimethylformamide, adding sodium hydride under ice bath cooling at 0°C, and stirring at room temperature after the addition is complete; (2) recooling to 0°C, adding (chloromethyl)trimethylsilane dropwise, and heating to 80°C for reaction after the addition is complete; (3) quenching, extraction, drying and separation of the reaction to obtain component B; and the molar ratio of the raw material, the sodium hydride and the (chloromethyl)trimethylsilane in step (1) to that in step (2) is 1.0:1.2:1.2. By adopting the above technical solution, component B is prepared by nucleophilic substitution reaction at a specific temperature and ratio, which can obtain a high-purity reaction precursor and reduce the influence of impurities on subsequent photocatalytic reactions.

[0017] Secondly, this invention provides a method for constructing a γ-amino acid backbone through photo-induced CO2 immobilization, employing the following technical solution:

[0018] A method for constructing a γ-amino acid backbone by photocatalytic CO2 fixation includes the following steps: S1. Mixing a photocatalyst, a base, component A, and component B, and replacing the atmosphere in the reaction vessel with high-purity carbon dioxide gas; S2. Injecting a solvent under a high-purity carbon dioxide gas atmosphere and saturating the solvent; S3. Placing the reaction vessel in a blue LED reactor equipped with a cooling device and stirring the reaction under light irradiation; S4. After the reaction is completed, post-processing the reaction mixture to obtain the target product.

[0019] By adopting the above technical solution, this method has the following advantages: It is carried out under normal temperature, pressure, and visible light conditions; the operation process is simple; and it is applicable to carbazole substrates and alkenes with different electronic effects substitution. Compared with traditional thermochemical methods, this method has lower energy consumption and higher chemical selectivity.

[0020] Preferably, in step S3, the wavelength of the blue LED reactor is 440nm-450nm, and the power is 30W-60W. By adopting the above technical solution, blue light of a specific wavelength and power can excite the photocatalyst, providing the energy required for the reaction. Combined with a cooling device, the temperature of the reaction system can be kept stable, reducing side reactions caused by thermal effects.

[0021] Preferably, in step S3, the temperature of the stirring reaction is 20℃-45℃, and the stirring reaction time is 12 hours-48 hours. By adopting the above technical solution, the reaction is carried out under near-room temperature conditions, which is beneficial to suppressing side reactions such as free radical coupling; the setting of the reaction time ensures that the substrate can be completely converted.

[0022] Preferably, step S4 specifically includes an in-situ esterification operation: after the reaction is complete, iodomethane is directly added to the mixture, the temperature is raised to 60°C and stirring is continued for in-situ esterification, and after cooling to room temperature, water is added and extracted with ethyl acetate to separate and obtain the target product; more preferably, the amount of iodomethane used is 4.0 times the molar amount of component A. By adopting the above technical solution, the highly polar carboxylic acid product is converted into an ester, which improves the lipophilicity of the product and facilitates subsequent separation and purification by extraction and chromatography, thereby improving the separation yield.

[0023] Preferably, in step S1, the molar ratio of component A to component B is 1.0:1.5. By adopting the above technical solution, using an excess of component B can compensate for possible free radical quenching losses during the reaction process and promote the complete conversion of component A as the acceptor.

[0024] This invention provides a method for constructing a γ-amino acid backbone through photo-induced CO2 immobilization. It has the following beneficial effects:

[0025] 1. This invention employs a visible light redox catalytic system, which can drive the reaction under a carbon dioxide atmosphere at room temperature and pressure. This avoids the high temperature and high pressure conditions typically required by traditional carbon dioxide conversion technologies, reducing energy consumption and the requirements for pressure-resistant equipment. Furthermore, the reaction system uses an organic photocatalyst, eliminating the need for transition metal reagents, thus avoiding heavy metal residue problems, improving the biosafety of the product, and conforming to the principles of green chemical synthesis.

[0026] 2. This invention utilizes the electronic effect of α-silicon groups to lower the oxidation potential of carbazole substrates, enabling the raw materials to undergo single-electron oxidation and remove silicon groups under mild light irradiation conditions, generating highly reactive α-amino carbon radicals. This activation strategy avoids the high energy barrier of directly activating inert CH bonds, achieving efficient carbon-carbon bond construction, improving the chemoselectivity and regioselectivity of the reaction, and effectively suppressing the occurrence of side reactions.

[0027] 3. The method of this invention has good substrate universality. It can react smoothly and obtain high yields for carbazole precursors with different electronic effect substituents and 1,1-stilbene substrates with different structures. This method can synthesize carbazole-containing γ-amino acid derivatives with complex structures in one step, providing a direct and efficient synthetic route for the construction of non-natural amino acid drug intermediates and optoelectronic material molecules. Attached Figure Description

[0028] Figure 1 This is a flowchart of the method of the present invention;

[0029] Figure 2 This diagram illustrates the construction of non-natural amino acid backbone fragments using the carbon dioxide photocatalytic strategy of this invention.

[0030] Figure 3 This is a schematic diagram of the reaction mechanism of the present invention;

[0031] Figure 4 This is a schematic diagram of the NMR data characterization of the present invention;

[0032] Figure 5 For the present invention 1 Schematic diagram of HNMR spectrum;

[0033] Figure 6 For the present invention 13 Schematic diagram of CNMR spectrum;

[0034] Figure 7 This is a schematic diagram of the HRMS spectrum of the present invention. Detailed Implementation

[0035] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0036] Please see the appendix Figure 1 -Appendix Figure 7 This invention provides a method for constructing a γ-amino acid backbone through photo-induced CO2 fixation, comprising:

[0037] 1,1-Diphenylethylene (C14H12, CAS No. 530-48-3); 1,1-Di(4-methylphenyl)ethylene (C16H16, CAS No. 2642-81-1).

[0038] Photocatalyst 4CzIPN (1,2,3,5-tetrakis(carbazole-9-yl)-4,6-dicyanobenzene, C56H32N6, CAS No. 1416881-52-1).

[0039] Photocatalyst 3DPAFIPN (2,4,5,6-tetratetra(diphenylamino)-1,3-phenylenedionitrile, C62H44N6, CAS No. 1639794-30-5).

[0040] Rhodamine B (C28H31ClN2O3, CAS No. 81-88-9).

[0041] (chloromethyl)trimethylsilane (C4H11ClSi, CAS No. 2344-80-1); 3,6-di-tert-butylcarbazole (C20H25N, CAS No. 2999-97-5).

[0042] 3,6-Dibromocarbazole (C12H7Br2N, CAS No. 6825-20-3); Cesium carbonate (Cs2CO3, CAS No. 534-17-8).

[0043] Potassium bicarbonate (KHCO3, CAS No. 298-14-6).

[0044] Other common auxiliary reagents, such as dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, iodomethane, sodium hydride, carbazole, and carbon dioxide gas, are all commercially available general chemicals.

[0045] 9-[(trimethylsilyl)methyl]-9H-carbazole (raw material A1): prepared by preparation example 1.

[0046] 3,6-Di-tert-butyl-9-[(trimethylsilyl)methyl]-9H-carbazole (raw material A2): prepared by preparation example 2.

[0047] 3,6-Dibromo-9-[(trimethylsilyl)methyl]-9H-carbazole (raw material A3): prepared by preparation example 3.

[0048] Preparation Example 1: This preparation example provides 9-[(trimethylsilyl)methyl]-9H-carbazole (starting material A1), comprising the following steps: Carbazole (1.67 g, 10.0 mmol) was added to a dry 250 mL round-bottom flask and dissolved in 30 mL of anhydrous N,N-dimethylformamide. The reaction mixture was cooled in an ice bath at 0 °C, and sodium hydride (60% mineral oil dispersion, 0.48 g, 12.0 mmol) was slowly added in batches. After the addition was complete, the ice bath was removed, and the mixture was stirred at room temperature for 45 minutes until no bubbles were generated. The reaction mixture was then cooled back to 0 °C, and (chloromethyl)trimethylsilane (1.47 g, 12.0 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was heated to 80 °C and reacted with stirring for 12 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction was quenched by adding 50 mL of saturated ammonium chloride aqueous solution. The mixture was extracted three times with 50 mL of ethyl acetate each time. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation under reduced pressure. The crude product was purified by silica gel column chromatography using a mixture of petroleum ether and ethyl acetate in a volume ratio of 50:1 as the eluent, yielding 2.28 g of a white solid product, 9-[(trimethylsilyl)methyl]-9H-carbazole, in 90% yield.

[0049] Preparation Example 2: This preparation example provides 3,6-di-tert-butyl-9-[(trimethylsilyl)methyl]-9H-carbazole (starting material A2), comprising the following steps: 3,6-di-tert-butylcarbazole (2.79 g, 10.0 mmol) was added to a dry 250 mL round-bottom flask and dissolved in 30 mL of anhydrous N,N-dimethylformamide. The reaction mixture was cooled in an ice bath at 0 °C, and sodium hydride (60% mineral oil dispersion, 0.48 g, 12.0 mmol) was slowly added in batches. After the addition was complete, the ice bath was removed, and the mixture was stirred at room temperature for 45 minutes until no bubbles were generated. The reaction mixture was then cooled back to 0 °C, and (chloromethyl)trimethylsilane (1.47 g, 12.0 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was heated to 80 °C and reacted with stirring for 12 hours. After the reaction was completed and cooled to room temperature, the reaction was quenched by adding 50 mL of saturated ammonium chloride aqueous solution. The mixture was extracted three times with 50 mL of ethyl acetate each time. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation under reduced pressure. The crude product was purified by silica gel column chromatography using a mixture of petroleum ether and ethyl acetate in a volume ratio of 60:1 as the eluent, to give 3.29 g of a white solid product, 3,6-di-tert-butyl-9-[(trimethylsilyl)methyl]-9H-carbazole, in 90% yield.

[0050] Preparation Example 3: This preparation example provides 3,6-dibromo-9-[(trimethylsilyl)methyl]-9H-carbazole (starting material A3), comprising the following steps: 3,6-dibromocarbazole (3.25 g, 10.0 mmol) was added to a dry 250 mL round-bottom flask and dissolved in 30 mL of anhydrous N,N-dimethylformamide. The reaction mixture was cooled in an ice bath at 0 °C, and sodium hydride (60% mineral oil dispersion, 0.48 g, 12.0 mmol) was slowly added in batches. After the addition was complete, the ice bath was removed, and the mixture was stirred at room temperature for 45 minutes until no bubbles were generated. The reaction mixture was then cooled back to 0 °C, and (chloromethyl)trimethylsilane (1.47 g, 12.0 mmol) was slowly added dropwise. After the addition was complete, the reaction mixture was heated to 80 °C and reacted with stirring for 12 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction was quenched by adding 50 mL of saturated ammonium chloride aqueous solution. The mixture was extracted three times with 50 mL of ethyl acetate each time. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation under reduced pressure. The crude product was purified by silica gel column chromatography using a mixture of petroleum ether and ethyl acetate in a volume ratio of 40:1 as the eluent, to give 3.53 g of a white solid product, 3,6-dibromo-9-[(trimethylsilyl)methyl]-9H-carbazole, in 86% yield.

[0051] Example 1: This example provides a method for constructing a γ-amino acid backbone by photo-induced CO2 fixation, comprising the following steps: In a 10 mL transparent reaction tube equipped with a magnetic stirrer, photocatalyst 4CzIPN (4.7 mg, 0.006 mmol), alkali cesium carbonate (195.5 mg, 0.6 mmol), 1,1-stilbene (36.0 mg, 0.2 mmol), and raw material A1 (9-[(trimethylsilyl)methyl]-9H-carbazole, 76.0 mg, 0.3 mmol) prepared in Example 1 are added sequentially. The reaction tube is sealed, and the gas inside the tube is replaced with high-purity carbon dioxide gas through three vacuum-gas cycles. Then, anhydrous dimethyl sulfoxide (DMSO, 2.0 mL) is injected using a syringe, and the mixture is stirred under carbon dioxide balloon pressure (1 atm) until the solvent is saturated. The reaction tube is placed in a blue LED reactor (wavelength 450 nm, power 30 W) equipped with a cooling device, the reaction temperature is controlled at 25 °C, and the reaction is stirred under light for 24 hours. After the reaction was complete, iodomethane (113.6 mg, 0.8 mmol) was added directly to the mixture, and the mixture was heated to 60 °C and stirred for 1 hour for in-situ esterification. After cooling to room temperature, water (10 mL) was added and the mixture was extracted with ethyl acetate (3 × 10 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and the residue was separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1) to give the target product methyl 4-([9H-carbazole-9-yl]-4,4-diphenylbutyrate, with a separation yield of 92%).

[0052] Example 2: This example provides a method for constructing a γ-amino acid backbone by photo-induced CO2 immobilization, comprising the following steps: In a 10 mL transparent reaction tube equipped with a magnetic stirrer, photocatalyst 4CzIPN (4.7 mg, 0.006 mmol), potassium bicarbonate (60.1 mg, 0.6 mmol), 1,1-stilbene (36.0 mg, 0.2 mmol), and raw material A1 (76.0 mg, 0.3 mmol) obtained in Preparation Example 1 are added sequentially. The gas replacement step is the same as in Example 1, with carbon dioxide introduced. Anhydrous dimethyl sulfoxide (DMSO, 2.0 mL) is injected. The reaction tube is placed in a blue LED reactor (wavelength 450 nm, power 60 W), and the reaction temperature is controlled at 35 °C. The reaction is stirred under light for 36 hours. After the reaction is completed, iodomethane (0.8 mmol) is added and esterification is carried out at 60 °C for 1 hour. The post-processing steps are the same as in Example 1, and the target product is obtained by column chromatography with a separation yield of 85%. Note: This example illustrates process conditions using a weak base (bicarbonate) and moderate temperature and time.

[0053] Example 3: This example provides a method for constructing a γ-amino acid backbone by photo-induced CO2 immobilization, comprising the following steps: In a 10 mL transparent reaction tube equipped with a magnetic stirrer, photocatalyst 4CzIPN (4.7 mg, 0.006 mmol), alkali cesium carbonate (195.5 mg, 0.6 mmol), 1,1-stilbene (36.0 mg, 0.2 mmol), and raw material A1 (76.0 mg, 0.3 mmol) obtained in Preparation Example 1 are added sequentially. The gas replacement step is the same as in Example 1, with carbon dioxide introduced. Anhydrous acetonitrile (MeCN, 2.0 mL) is injected. The reaction tube is placed in a blue LED reactor (wavelength 450 nm, power 60 W), and the reaction temperature is controlled at 45 °C. The reaction is stirred under light for 48 hours. After the reaction is completed, iodomethane (0.8 mmol) is added and esterification is carried out at 60 °C for 1 hour. The post-processing steps are the same as in Example 1, and the target product is obtained by column chromatography with a separation yield of 65%. Note: This example demonstrates the high-end values ​​of process parameters (45°C, 48 hours) and the applicability of different solvent systems.

[0054] Example 4: This example provides a method for constructing a γ-amino acid backbone by photo-induced CO2 immobilization, comprising the following steps: In a 10 mL transparent reaction tube equipped with a magnetic stirrer, photocatalyst 3DPAFIPN (5.8 mg, 0.006 mmol), alkali cesium carbonate (195.5 mg, 0.6 mmol), 1,1-stilbene (36.0 mg, 0.2 mmol), and raw material A1 (76.0 mg, 0.3 mmol) obtained in Preparation Example 1 are added sequentially. The gas replacement step is the same as in Example 1, with carbon dioxide introduced. Anhydrous dimethyl sulfoxide (DMSO, 2.0 mL) is injected. The reaction tube is placed in a blue LED reactor (wavelength 440 nm, power 30 W), and the reaction temperature is controlled at 20 °C. The reaction is stirred under light for 12 hours. After the reaction is completed, iodomethane (0.8 mmol) is added and esterification is carried out at 60 °C for 1 hour. The post-processing steps are the same as in Example 1, and the target product is obtained by column chromatography with a separation yield of 52%. Note: This example demonstrates the low-end values ​​of process parameters (20°C, 12 hours) and the applicability of different photocatalysts.

[0055] Example 5: This example provides a method for constructing a γ-amino acid backbone by photo-catalyzed CO2 immobilization, comprising the following steps: In a 10 mL transparent reaction tube equipped with a magnetic stir bar, the organic dye photocatalyst Rhodamine B (2.9 mg, 0.006 mmol), alkali cesium carbonate (195.5 mg, 0.6 mmol), 1,1-stilbene (36.0 mg, 0.2 mmol), and raw material A1 (76.0 mg, 0.3 mmol) obtained in Preparation Example 1 are added sequentially. The gas replacement step is the same as in Example 1, with carbon dioxide introduced. Anhydrous dimethyl sulfoxide (DMSO, 2.0 mL) is injected. The reaction conditions are controlled at room temperature (approximately 25 °C) and blue LED illumination (30 W) for 24 hours. After the reaction, iodomethane (0.8 mmol) is added and esterification is performed at 60 °C for 1 hour. The post-processing steps are the same as in Example 1, and the target product is obtained by column chromatography with a separation yield of 58%. Note: This example verifies the feasibility of using inexpensive organic dyes as catalysts.

[0056] Example 6: This example provides a method for constructing a γ-amino acid backbone by photo-induced CO2 fixation, comprising the following steps: In a 10 mL transparent reaction tube equipped with a magnetic stirrer, photocatalyst 4CzIPN (4.7 mg, 0.006 mmol), alkali cesium carbonate (195.5 mg, 0.6 mmol), 1,1-stilbene (36.0 mg, 0.2 mmol), and raw material A2 (3,6-di-tert-butyl-9-[(trimethylsilyl)methyl]-9H-carbazole, 109.6 mg, 0.3 mmol) obtained in Preparation Example 2 were added sequentially. The gas replacement step was the same as in Example 1, with carbon dioxide introduced. Anhydrous dimethyl sulfoxide (DMSO, 2.0 mL) was injected. The reaction conditions were controlled at room temperature (approximately 25 °C) and blue LED illumination (30 W) for 24 hours. After the reaction was completed, iodomethane (0.8 mmol) was added and esterification was carried out at 60 °C for 1 hour. The post-processing steps were the same as in Example 1. The target product, methyl 4-(3,6-di-tert-butyl-9H-carbazole-9-yl)-4,4-diphenylbutyrate, was obtained by column chromatography with a separation yield of 88%. Note: This example verifies the reactivity of the carbazole precursor containing a sterically hindered electron-donating group.

[0057] Example 7: This example provides a method for constructing a γ-amino acid backbone by photo-induced CO2 fixation, comprising the following steps: In a 10 mL transparent reaction tube equipped with a magnetic stirrer, photocatalyst 4CzIPN (4.7 mg, 0.006 mmol), alkali cesium carbonate (195.5 mg, 0.6 mmol), 1,1-di(4-methylphenyl)ethylene (41.7 mg, 0.2 mmol), and raw material A3 (3,6-dibromo-9-[(trimethylsilyl)methyl]-9H-carbazole, 123.4 mg, 0.3 mmol) obtained in Preparation Example 3 were added sequentially. The gas replacement step was the same as in Example 1, with carbon dioxide introduced. Anhydrous dimethyl sulfoxide (DMSO, 2.0 mL) was injected. The reaction conditions were controlled at room temperature (approximately 25 °C) and blue LED illumination (30 W) for 24 hours. After the reaction was completed, iodomethane (0.8 mmol) was added and esterification was carried out at 60 °C for 1 hour. The post-processing steps were the same as in Example 1. The target product, methyl 4-(3,6-dibromo-9H-carbazole-9-yl)-4,4-di(4-methylphenyl)butyrate, was obtained by column chromatography with a separation yield of 76%. Note: This example verifies the reactivity of the carbazole precursor with simultaneous changes in olefin substrate and electron-withdrawing group substitution, demonstrating functional group compatibility.

[0058] Example 8: This example provides a method for constructing a γ-amino acid backbone using photo-induced CO2 immobilization (gram-scale experiment), comprising the following steps: In a 100 mL pressure-resistant reaction flask equipped with a magnetic stirrer, photocatalyst 4CzIPN (47.0 mg, 0.06 mmol), alkali cesium carbonate (1.95 g, 6.0 mmol), 1,1-stilbene (360.0 mg, 2.0 mmol), and raw material A1 obtained in Preparation Example 1 (760.0 mg, 3.0 mmol) were added sequentially. The reaction flask was sealed and replaced with a carbon dioxide atmosphere. Anhydrous dimethyl sulfoxide (DMSO, 20 mL) was injected and CO2 was saturated. The reaction conditions were controlled at room temperature (approximately 25 °C), and the reaction was stirred under high-power blue LED light source (60 W) for 36 hours. After the reaction was completed, iodomethane (8.0 mmol) was added and esterification was performed at 60 °C for 1 hour. After routine post-processing and separation by column chromatography, 756 mg of the target product was obtained, with a separation yield of 90%. Note: This embodiment verifies the scale-up potential of this method.

[0059] Comparative Example 1:

[0060] Compared with Example 1, the difference is that no light is applied during the reaction process. Instead, the reaction tube is wrapped with aluminum foil to protect it from light and stirred in the dark for 24 hours. All other raw materials, proportions and operating steps are the same.

[0061] Comparative Example 2:

[0062] Compared with Example 1, the difference is that the photocatalyst 4CzIPN is not added to the reaction system, while the other raw materials, ratios and operating steps are the same.

[0063] Comparative Example 3:

[0064] Compared with Example 1, the difference is that 9-methyl-9H-carbazole (0.3 mmol) is used to replace raw material A1 (9-[(trimethylsilyl)methyl]-9H-carbazole), that is, the molecular structure does not contain trimethylsilyl groups that can assist in the oxidation and desilication to generate free radicals. The other raw materials, ratios and operation steps are the same.

[0065] Note: This comparative example is used to demonstrate the crucial role of introducing “$\alpha$-silicon-based” in achieving the reaction under mild conditions.

[0066] Comparative Example 4:

[0067] Compared with Example 1, the difference is that cesium carbonate is not added to the reaction system, while the other raw materials, proportions and operating steps are the same.

[0068] Comparative Example 5:

[0069] Compared with Example 1, the difference is that the reaction system does not contain the photocatalyst 4CzIPN and is not exposed to light. Instead, the reaction temperature is raised to 100°C and stirred for 24 hours (to try the thermal initiation route). The other raw materials, proportions and operation steps are the same.

[0070] Test case

[0071] Test Example 1: Product Structure Confirmation

[0072] This test case aims to confirm the chemical structure of compound P1 (4-(9H-carbazole-9-yl)-4,4-diphenylbutyrate methyl ester) prepared in Example 1.

[0073] Experimental method: 20 mg of the white solid sample purified by column chromatography in Example 1 was dissolved in 0.5 mL of deuterated chloroform (CDCl3), and nuclear magnetic resonance spectroscopy (600 MHz) was used for analysis. 1 HNMR and 13 CNMR assay. Another 1 mg sample was dissolved in chromatographic grade methanol, and its precise molecular weight was determined using a high-resolution mass spectrometer (HRMS-ESI) in positive ion mode.

[0074] Experimental data: The spectroscopic data of the obtained products are summarized in Table 1.

[0075] Table 1 Summary of structural characterization data of product P1 obtained in Example 1

[0076]

[0077]

[0078] Test Example 2: Comparative Analysis of Reaction Performance

[0079] This test case aims to examine the influence of different reaction conditions on reaction efficiency and to verify the necessity of each key element in the technical solution of this invention.

[0080] Experimental methods: Reaction conditions were set for Examples 1-8 and Comparative Examples 1-5. After the reaction was completed, a standard internal standard (mesene) was added to the reaction system. Samples were filtered through a microporous membrane, and the product conversion rate and separation yield were determined using gas chromatography (GC) or high performance liquid chromatography (HPLC). The experiment was repeated three times, and the average value was taken.

[0081] Experimental data: The yield data of each group of experiments are summarized in Table 2.

[0082] Table 2. Yield data of target product separation under different reaction conditions.

[0083]

[0084]

[0085] Based on Table 1 and the above experimental results, the analysis is as follows:

[0086] The extremely low or undetectable yields of Comparative Example 1 (no light) and Comparative Example 2 (no photocatalyst) indicate that the reaction cannot proceed spontaneously under light-free conditions. Comparative Example 5 failed to effectively obtain the target product under high-temperature conditions, suggesting that the photocatalytic system has a unique reaction pathway rather than a simple thermal effect.

[0087] Example 1 achieved a yield of 92.3%, while Comparative Example 3, using a structurally similar but silicon-free 9-methyl-9H-carbazole, only achieved a yield of 2.8%. This data indicates that the α-silicon group in the starting material molecule is crucial for the reaction. The σ-p hyperconjugation effect generated by the silicon group lowers the oxidation potential of the nitrogen atom, allowing the substrate to be oxidized by the excited-state photocatalyst and undergo desilication, thereby generating active free radicals. Silicon-free substrates, due to oxidation potential mismatch or the inability to undergo specific desilication, result in an inhibited reaction.

[0088] The results of Examples 2 to 5 show that the reaction system is adaptable to the strength of the base, the type of solvent, and the type of catalyst (metal-containing / metal-free / organic dye), and can achieve conversion under different conditions. Examples 6 to 8 confirm that the method is applicable to substrates with different electronically effective substituents, and the yield does not show significant decline at gram-scale preparation.

[0089] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A reaction composition for photo-induced CO2 fixation to construct a γ-amino acid backbone, characterized in that, The composition comprises the following components in molar amounts: Component A: 1.0 part; Component B: 1.2-2.5 parts; Photocatalyst: 0.005-0.06 parts; Alkali: 1.5-6.0 parts; and carbon dioxide gas; wherein, component A is selected from 1,1-stilbene or 1,1-di(4-methylphenyl)ethylene; and component B is selected from 9-[(trimethylsilyl)methyl]-9H-carbazole, 3,6-di-tert-butyl-9-[(trimethylsilyl)methyl]-9H-carbazole or 3,6-dibromo-9-[(trimethylsilyl)methyl]-9H-carbazole.

2. The reaction composition for constructing a γ-amino acid backbone by photo-induced CO2 fixation according to claim 1, characterized in that, The photocatalyst is selected from 4CzIPN, 3DPAFIPN, or Rhodamine B.

3. The reaction composition for constructing a γ-amino acid backbone by photo-induced CO2 fixation according to claim 1, characterized in that, The alkali is selected from cesium carbonate or potassium bicarbonate.

4. The reaction composition for constructing a γ-amino acid backbone by photo-induced CO2 fixation according to claim 1, characterized in that, The composition further comprises a solvent selected from dimethyl sulfoxide or acetonitrile, and the amount of solvent used is such that the concentration of component A in the solvent is 0.05-0.25 mol / L.

5. The reaction composition for constructing a γ-amino acid backbone by photo-induced CO2 fixation according to claim 1, characterized in that, Component B is prepared by a method comprising the following steps: (1) Dissolve the raw material selected from carbazole, 3,6-di-tert-butylcarbazole or 3,6-dibromocarbazole in anhydrous N,N-dimethylformamide, add sodium hydride under ice bath cooling at 0°C, and stir at room temperature after the addition is complete. (2) Cool back to 0°C, add (chloromethyl)trimethylsilane dropwise, and heat to 80°C after the addition is complete; (3) After the reaction is completed, the component B is obtained by quenching, extraction, drying and separation. The molar ratio of the raw materials in step (1), the sodium hydride, and the (chloromethyl)trimethylsilane in step (2) is 1.0:1.2:1.

2.

6. A method for constructing a γ-amino acid backbone by photo-induced CO2 fixation according to any one of claims 1-5, characterized in that, Includes the following steps: S1. Mix the photocatalyst, the base, component A and component B, and replace the atmosphere in the reaction vessel with high-purity carbon dioxide gas; S2. Inject the solvent under a high-purity carbon dioxide gas atmosphere and saturate the solvent; S3. Place the reaction vessel in a blue LED reactor equipped with a cooling device and stir the reaction under light; S4. After the reaction is complete, the reaction mixture is post-treated to obtain the target product.

7. The method for constructing a γ-amino acid backbone by photo-induced CO2 immobilization according to claim 6, characterized in that, In step S3, the wavelength of the blue LED reactor is 440nm-450nm, and the power is 30W-60W.

8. The method for constructing a γ-amino acid backbone by photo-induced CO2 immobilization according to claim 6, characterized in that, In step S3, the temperature of the stirring reaction is 20℃-45℃, and the stirring reaction time is 12 hours-48 hours.

9. The method for constructing a γ-amino acid backbone by photo-induced CO2 immobilization according to claim 6, characterized in that, Step S4 specifically includes in-situ esterification: after the reaction is complete, iodomethane is added directly to the mixture, the temperature is raised to 60°C and stirring is continued for in-situ esterification, after cooling to room temperature, water is added and extracted with ethyl acetate to separate and obtain the target product; preferably, the amount of iodomethane used is 4.0 times the molar amount of component A.

10. The method for constructing a γ-amino acid backbone by photo-induced CO2 immobilization according to claim 6, characterized in that, In step S1, the molar ratio of component A to component B is 1.0:1.5.

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