A method for preparing photocatalytic γ-hydroxycarboxylic acid compounds

Abstract

This invention belongs to the field of organic chemical synthesis technology and discloses a photocatalytic method for preparing γ-hydroxycarboxylic acid compounds. Using alkyl aldehydes, olefins, and CO2 as raw materials, 3DPAFIPN as a photocatalyst, and TMEDA as the XAT reagent, a series of γ-hydroxycarboxylic acid compounds are prepared in a one-pot process under light irradiation. This invention is the first to achieve the photocatalytic three-component carboxylation reaction of aliphatic aldehydes, CO2, and olefins to synthesize γ-hydroxycarboxylic acids, filling a gap in existing technologies. The method of this invention features mild process conditions, a short process flow, simple steps, and wide substrate applicability, meeting the requirements of industrial production. Studies have shown that the product yield can reach 77%, and the generated γ-hydroxycarboxylic acid compounds have broad application prospects in organic synthesis and drug development. Therefore, this invention has significant application value.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, and relates to the preparation of a series of γ-hydroxycarboxylic acid compounds by reacting inexpensive and readily available alkyl aldehydes with olefins and CO2 under visible light induction. Background Technology

[0002] γ-Hydroxycarboxylic acid derivatives are widely found in natural products, bioactive molecules, and pharmaceutical molecules, such as fluoxetine, ezetimibe tablets, eldanolide, and stemonamide, which have shown good efficacy in antidepressant and cholesterol-lowering effects, respectively. Furthermore, hydroxycarboxylic acids are also one of the most common functional groups in organic chemistry, playing a crucial role in synthetic chemistry. Therefore, developing efficient new synthetic methods for hydroxycarboxylic acid compounds is of great significance.

[0003] Currently, many synthetic methods for γ-hydroxycarboxylic acid compounds have been reported [see: (a) Carbon Nanotube / Zeolite Hybrid Catalysts for Glucose Conversion in Water / Oil Emulsions, ACS Catal. 2015, 5, 4761-4771. (b) Combination of Metal-Catalyzed CycloisoMerization and Biocatalysis in Aqueous Media: Asymmetric Construction of Chiral Alcohols, Lactones, and γ-Hydroxy-Carbonyl Compounds, ACS Catal. 2017, 7, 7753–7759. (c) Highly active bidentate N-heterocyclic carbene / ruthenium complexes performing dehydrogenative coupling of alcohols and hydroxides in open air, Chem. Commun. 2019, 55, 8591-8594. (d) Carboxyl Group-Directed Iridium-Catalyzed Enantioselective Hydrogenation of Aliphatic γ-Ketoacids, ACS Catal. 2020, 10, 10032-10039. (e) Iridium-Catalyzed Asymmetric Hydrogenation of γ- and δ-Ketoacids for Enantioselative Synthesis of γ- and δ-Lactones, Org. Lett. 2020, 22, 818-822. (f) Selective Oxidation of 1,3-Butanediolto 3-Hydroxybutyric Acid over PtSb2 Alloy, ACS Sustainable Chem. Eng. 2023, 11, 587-596.] The methods are summarized as hydrogenation of γ-keto acid derivatives, 4-pentyne acid cyclic isomerization and hydrolysis, dehydrogenation coupling of alcohols and hydroxides, selective oxidation, and HMF hydrolysis hydrogenation, etc.However, the above reactions still have some drawbacks, such as harsh reaction conditions, the need for prefunctionalization, limited substrate range, and expensive catalysts. Therefore, developing a simple reaction system that uses inexpensive and readily available raw materials aldehydes and alkenes to react with abundant C1 resource CO2 under visible light catalysis to synthesize γ-hydroxycarboxylic acid derivatives has significant research value and application potential.

[0004] Alkyl aldehydes are a class of abundant raw material chemicals, commonly found in simple structural units, natural products, and pharmaceutical molecules. Alkyl aldehydes are converted in one step to the corresponding α-ester bromides via benzoyl bromide, and under visible light induction, they can react with XAT reagents to generate alkyl radicals. On the other hand, CO2 is an abundant, ubiquitous, inexpensive, and non-toxic gas in nature. Over the past few decades, many useful organic chemicals have been produced using CO2 as a raw material. Currently, efforts are focused on developing technologies to convert CO2 into various high-value-added chemicals; however, CO2 conversion remains a significant challenge. A key issue is that, due to its high thermodynamic stability and kinetic inertness, it often requires harsh and demanding reaction conditions. Therefore, developing new and efficient catalytic strategies to broaden the product range using CO2 as a raw material under mild conditions remains crucial. Furthermore, alkenes are the most common structural units in organic compounds, and their bifunctionalization has been one of the most researched directions in organic synthesis methodology in recent years, exhibiting high atom economy and step economy. Therefore, the strategy of converting alkyl aldehydes into alkyl radicals in a one-pot XAT process under photocatalysis, which are then captured by olefins and reduced by a photocatalyst to generate carbanions that nucleophilically add CO2 to form γ-hydroxycarboxylic acids, achieves both the bifunctionalization of olefins and the conversion of CO2. This is a synthetic method of great research significance.

[0005] This invention utilizes readily available and inexpensive alkyl aldehydes as raw materials, converting them in a one-step process with benzoyl bromide to stable alkyl bromides. This one-pot method, without complex post-processing, employs the readily available and inexpensive organic photocatalyst 3DPAFIPN. Upon visible light excitation, the alkyl radicals undergo an XAT process with TMEDA to generate alkyl radicals, which then react with olefins and CO2 to produce a series of γ-hydroxycarboxylic acid derivatives. Compared to traditional synthetic methods, visible light, as a green energy source, offers milder reaction conditions and better functional group compatibility, thus providing a new approach for the green and efficient synthesis of γ-hydroxycarboxylic acid compounds. Summary of the Invention

[0006] This invention provides a novel synthetic method for preparing γ-hydroxycarboxylic acids by using easily synthesized 3DPAFIPN as a photocatalyst and readily available and inexpensive TMEDA as an XAT reagent, promoting the carboxylation reaction of aldehydes with olefins and CO2 under photoexcitation. This method has advantages such as convenient experimental operation, good substrate compatibility, and readily available and inexpensive raw materials, thus possessing significant application value and socio-economic benefits.

[0007] The technical solution of the present invention:

[0008] A photocatalytic method for preparing γ-hydroxycarboxylic acid compounds is disclosed, using alkyl aldehydes, olefins, and CO2 as raw materials, 3DPAFIPN as a photocatalyst, and TMEDA as an XAT reagent, to prepare a series of γ-hydroxycarboxylic acid compounds in a one-pot process under light irradiation; the synthetic route is as follows:

[0009]

[0010] R of alkyl aldehydes 1 It is phenethyl, substituted phenethyl, hydrogen, alkyl borate ester;

[0011] R of olefins 2 It is methoxy, chlorine, benzofuran, methyl, and imidazole;

[0012] The steps are as follows:

[0013] (1) Alkyl aldehyde (1), benzoyl bromide and zinc bromide were dissolved in dichloromethane and stirred at room temperature for 2 hours. After filtration, the solvent was evaporated and the ester bromide (1') was generated in situ by one-pot method.

[0014] (2) Photocatalyst, base, and 5A molecular sieve are added to the in-situ generated ester bromide (1'). After adding solvent, XAT (halogen atom transfer) reagent and olefin (2) under CO2 atmosphere, the reaction is irradiated under blue light to synthesize γ-hydroxycarboxylic acid compounds (3).

[0015] The solvent is selected from toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetone and acetonitrile;

[0016] The photocatalysts were selected from 3DPAFIPN, 4CzIPN, sodium fluorescein, and Acid Red 94;

[0017] XAT reagents are selected from TMEDA, DIPEA and (TMS)3SiH;

[0018] The base is selected from K3PO4 and Na2CO. 3、 Cs2CO3, t-BuOK;

[0019] The concentration of alkyl aldehyde in the reaction system is 0.1 M;

[0020] The molar ratio of alkyl aldehyde, benzoyl bromide, and zinc bromide is 1:1.05:0.1;

[0021] The molar ratio of alkyl aldehydes to olefins is 1:1 to 1:3;

[0022] The molar ratio of alkyl aldehyde to photocatalyst is 1:0.01;

[0023] The molar ratio of alkyl aldehyde to XAT reagent is 1:1 to 1:3;

[0024] The molar ratio of alkyl aldehyde to base is 1:1 to 1:3;

[0025] The concentration of 5A molecular sieve in solution is 50 mg / mL;

[0026] The filtration in step (1) uses neutral alumina;

[0027] The reaction time in step (2) is 12h to 24h;

[0028] The wavelength in step (2) is 390nm to 456nm;

[0029] The reaction temperature in step (2) is -10℃ to 25℃.

[0030] The beneficial effects of this invention are as follows: This invention provides a method for preparing γ-hydroxycarboxylic acids, achieving for the first time the synthesis of γ-hydroxycarboxylic acids through photocatalytic carboxylation of aliphatic aldehydes with olefins and CO2, filling a gap in existing technologies. The method of this invention features mild process conditions, a short process flow, simple steps, and broad substrate applicability, meeting the requirements of industrial production. Studies have shown that the product yield can reach 77%, and the generated γ-hydroxycarboxylic acid compounds have broad application prospects in organic synthesis and drug development. Therefore, this invention has significant application value. Attached Figure Description

[0031] Figure 1 For compound 3a 1 H-NMR spectrum.

[0032] Figure 2 For compound 3a 13 C-NMR spectrum.

[0033] Figure 3 For compound 3b 1 H-NMR spectrum.

[0034] Figure 4 For compound 3b 13 C-NMR spectrum.

[0035] Figure 5 For compound 3c1 H-NMR spectrum.

[0036] Figure 6 For compound 3c 13 C-NMR spectrum.

[0037] Figure 7 For compound 3d 1 H-NMR spectrum.

[0038] Figure 8 For compound 3d 13 C-NMR spectrum.

[0039] Figure 9 For compound 3e 1 H-NMR spectrum.

[0040] Figure 10 For compound 3e 13 C-NMR spectrum.

[0041] Figure 11 For compound 3f 1 H-NMR spectrum.

[0042] Figure 12 For compound 3f 13 C-NMR spectrum.

[0043] Figure 13 3g of compound 1 H-NMR spectrum.

[0044] Figure 14 3g of compound 13 C-NMR spectrum.

[0045] Figure 15 For compound 3h 1 H-NMR spectrum.

[0046] Figure 16 For compound 3h 13 C-NMR spectrum.

[0047] Figure 17 For compound 3i 1 H-NMR spectrum.

[0048] Figure 18 For compound 3i 13 C-NMR spectrum.

[0049] Figure 19 For compound 3j 1 H-NMR spectrum.

[0050] Figure 20 For compound 3j 13C-NMR spectrum. Detailed Implementation

[0051] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings and technical solutions.

[0052] Example 1: Synthesis of 4-(benzoyloxy)-2,6-diphenylhexanoic acid (3a)

[0053]

[0054] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and then stirred at 25 °C for 10 min. Subsequently, phenylpropionaldehyde (27 μL, 0.2 mmol) was added to the system, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ and used directly in the next step without further purification. The Schlenk reaction flask containing the alkyl bromide product was placed in a glove box, and 4CzIPN (1.6 mg, 0.01 mmol), K₃PO₄ (126 mg, 0.6 mmol), and 5A molecular sieve (100 mg) were added. The reaction mixture was then removed from the glove box and subjected to three CO2 purgings in a double-row tube. DMA (2 mL, 0.1 M), styrene (23 μL, 0.2 mmol), and TMEDA (30 μL, 0.2 mmol) were added sequentially under a CO2 atmosphere. The mixture was stirred for 12 hours at 25°C under blue LEDs (390 nm). After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by rapid chromatography. The yield of 4-(benzoyloxy)-2,6-diphenylhexanoic acid was 71%. 1 H NMR (500MHz, CDCl3) δ8.02 (dd, J=8.3, 1.3Hz, 0.9H), 7.97 (dd, J=8.0, 1.5Hz, 1.1H), 7.55-7.50 (m, 1H), 7.44-7.38 (m, 2H), 7.29-7 .13(m,5H),5.19-5.15(m,0.6H),5.02-4.98(m,0.4H),3.64-3.58(m,2.7H),3.39(s,1.3H),2.62-2.37(m,2H),2.03-1.62(m,7H). 13C NMR (101MHz, CDCl3) δ174.36,173.95,166.56,166.40,139.14,138.69,133.05,132.96,130.54,130.46,129.82,129.74,128.90,128.85,128.5 0,128.43,128.13,127.80,127.62,127.44,75.93,75.64,52.85,52.08 ,48.34,47.95,39.73,39.43,36.09,35.95,24.51,24.34,18.48,18.05.

[0055] Example 2: Synthesis of 1-(4-cyanophenyl)-6-methoxy-6-oxo-5-phenylhexan-3-yl benzoate (3b)

[0056]

[0057] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and the mixture was stirred at 25 °C for 10 min. Then, 4-cyanophenylpropanal (29 μL, 0.2 mmol) was added, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ to obtain the alkyl bromide product, which could be directly used in the next step without further purification. The reaction flask containing the alkyl bromide product was placed in a glove box, and sodium fluorescein (0.8 mg, 0.01 mmol), t-BuOK (67 mg, 0.6 mmol), and 5A molecular sieve (100 mg) were added. The reaction mixture was then removed from the glove box and subjected to three CO2 purgings in a double-row tube. THF (2 mL, 0.1 M), styrene (69 μL, 0.6 mmol), and TMEDA (30 μL, 0.2 mmol) were added sequentially under a CO2 atmosphere. The mixture was stirred at 25°C under blue LEDs (456 nm) for 24 hours. After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. 2 mL of diethyl ether and 0.5 mL of methanol were added, and the mixture was placed at 0°C. 2 M TMSCH2N2 (200 μL, 0.4 mmol) was slowly added dropwise, and the mixture was stirred at this temperature for 0.5 h. The solvent was evaporated to dryness, and the residue was purified by rapid chromatography. The yield of 1-(4-cyanophenyl)-6-methoxy-6-oxy-5-phenylhexane-3-ylbenzoate was 65%. 1H NMR(500MHz, CDCl3)δ8.06(d,J=7.2Hz,0.9H),8.00(d,J=7.2Hz,1.1H),7.59-7.41(m,3H),7.33-7.18(m,5H),5.11-5.06(m ,0.5H),4.94-4.89(m,0.5H),3.69-3.60(m,2.7H),3.41(s,1.3H),2.59-2.50(m,1H),2.15-1.90(m,2H),1.01-0.91(m,6H). 13C NMR (101MHz, CDCl3) δ174.09,173.74,166.17,166.02,147.01,146.87,138.67,138.29 ,133.31,133.23,132.33,132.29,130.01,129.95,129.70,129.62,129.22,129.17,12 8.97, 128.91, 128.52, 128.46, 127.99, 127.72, 127.57, 119.03, 119.02, 109.98, 109.95, 72.47, 72.15, 52.29, 52.15, 48.23, 47.91, 38.19, 37.95, 35.73, 35.68, 31.92, 31.72.

[0058] Example 3: Synthesis of 6-methoxy-1-(4-methoxyphenyl)-6-oxo-5-phenylhexan-3-yl benzoate (3c)

[0059]

[0060] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and the mixture was stirred at 25 °C for 10 min. Then, 4-methoxyphenylpropanal (32 mg, 0.2 mmol) was added, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ to obtain the alkyl bromide product, which could be directly used in the next step without further purification. The reaction flask containing the alkyl bromide product was placed in a glove box, and 3DPAFIPN (1.5 mg, 0.01 mmol), Na₂CO₃ (63 mg, 0.6 mmol), and 5A molecular sieve (100 mg) were added. The glove box was then removed, and three CO2 purgings were performed on a double-row tube. Toluene (2 mL, 0.1 M), styrene (23 μL, 0.2 mmol), and TMEDA (90 μL, 0.6 mmol) were added sequentially under a CO2 atmosphere. The reactor was placed at -78 °C for 2 min under a CO2 atmosphere. The resulting mixture was then brought to room temperature and stirred under blue LEDs (455 nm) at -10 °C for 12 h. After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. 2 mL of diethyl ether and 0.5 mL of methanol were added, and the mixture was placed at 0 °C. 2 M TMSCH2N2 (200 μL, 0.4 mmol) was slowly added dropwise, and the mixture was stirred at this temperature for 0.5 h. The solvent was evaporated to dryness, and the residue was purified by rapid chromatography. The yield of 6-methoxy-1-(4-methoxyphenyl)-6-oxo-5-phenylhexane-3-ylbenzoate was 59%. 1 H NMR (400MHz, CDCl3) δ7.95(d,J=6.8Hz,0.7H),7.90(d,J=6.8Hz,1.3H),7.51-7.46(m,1H),7.40-7.34(m,2H),7.23-7.12(m,5H),7.00-6.93(m,2H) ,6.72-6.68(m,2H),5.20-5.13(m,0.6H),5.02-4.96(m,0.4H),3.67-3.5 9(m,4H),3.52(s,2H),3.39(s,1H),2.61-2.48(m,3H),2.14-1.77(m,3H). 13C NMR (101MHz, CDCl3) δ174.27,173.88,166.68,166.11,157.97,138.93,138.55,133. 49,133.36,133.11,133.02,130.40,130.33,129.78,129.71,129.30,129.27,128.9 4,128.89,128.49,128.42,128.06,127.82,127.64,127.51,113.96,113.93,72.91,72.71,55.33,52.27,52.13,48.37,47.99,38.18,38.01,36.72,36.61,30.81,30.65.

[0061] Example 4: Synthesis of 5-methoxy-5-oxo-4-phenylpentan-2-yl benzoate (3d)

[0062]

[0063] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and the mixture was stirred at 25 °C for 10 min. Acetaldehyde (11 μL, 0.2 mmol) was then added, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ to obtain the alkyl bromide product, which could be used directly in the next step without further purification. The reaction flask containing the alkyl bromide product was placed in a glove box, and 3DPAFIPN (1.5 mg, 0.01 mmol), K₃PO₄ (42 mg, 0.2 mmol), and 5A molecular sieve (100 mg) were added. The reaction mixture was then removed from the glove box and subjected to three CO2 purgings in a double-row tube. DMSO (2 mL, 0.1 M), styrene (23 μL, 0.2 mmol), and TMEDA (30 μL, 0.2 mmol) were added sequentially under a CO2 atmosphere. The mixture was stirred for 24 hours at 25°C under blue LEDs (440 nm) irradiation. After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. 2 mL of diethyl ether and 0.5 mL of methanol were added, and the mixture was placed at 0°C. 2 M TMSCH2N2 (200 μL, 0.4 mmol) was slowly added dropwise, and the mixture was stirred at this temperature for 0.5 h. The solvent was evaporated to dryness, and the residue was purified by rapid chromatography. The yield of 5-methoxy-5-oxy-4-phenylpentane-2-ylbenzoate was 67%. 1 H NMR(400MHz, CDCl3)δ8.09(d,J=6.8Hz,0.8H),8.03(d,J=7.2Hz,1.2H),7.64-7.58(m,1H),7.52-7.46(m,2H),7.37-7.27(m,5H),5.27-5.20 (m,0.6H),5.08-5.00(m,0.4H),3.83-3.77(m,1H),3.67(s,1.8H),3. 58(s,1.2H),2.69-2.53(m,1H),2.24-2.14(m,1H),1.44-1.37(m,3H). 13C NMR (101MHz, CDCl3) δ174.25,173.93,166.13,165.98,138.91,138.52,133.04,132.95,130.65,130.58,129.73,129.66,128.97, 128.92,128.47,128.40,128.04,127.87,127.65,127.54,70.07,69.86,52.26,52.15,48.48,48.14,39.86,39.83,20.58,20.44.

[0064] Example 5: 1-Methoxy-1-oxo-2-phenyl-7-(4,4,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)heptane-4-ylbenzoate

[0065] Synthesis of 3-dioxaborolan-2-yl)heptan-4-yl benzoate(3e)

[0066]

[0067] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and the mixture was stirred at 25 °C for 10 min. Then, 4-(4,4,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)butanal (44 μL, 0.2 mmol) was added, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ to obtain the alkyl bromide product, which could be directly used in the next step without further purification. The reaction flask containing the alkyl bromide product was placed in a glove box, and 3DPAFIPN (6.5 mg, 0.01 mmol), K₃PO₄ (42 mg, 0.2 mmol), and 5A molecular sieve (100 mg) were added. The glove box was then removed, and three CO2 replacements were performed on a double-row tube. Toluene (2 mL, 0.1 M), styrene (23 μL, 0.2 mmol), and (TMS)3SiH (54 mg, 0.6 mmol) were added sequentially under a CO2 atmosphere. The reactor was placed at -78 °C for 2 min under a CO2 atmosphere. The resulting mixture was then brought to room temperature and stirred at 25 °C under blue LEDs (455 nm) for 12 h. After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. 2 mL of diethyl ether and 0.5 mL of methanol were added, and the mixture was placed at 0 °C. 2 M TMSCH2N2 (200 μL, 0.4 mmol) was slowly added dropwise, and the mixture was stirred at this temperature for 0.5 h. The solvent was evaporated to dryness, and the residue was purified by rapid chromatography. The yield of 1-methoxy-1-oxo-2-phenyl-7-(4,4,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)heptane-4-ylbenzoate was 44%. 1 H NMR(500MHz, CDCl3)δ8.02(d,J=7.0Hz,0.9H),7.98(d,J=7.0Hz,1.1H),7.57-7.53(m ,1H),7.46-7.41(m,2H),7.31-7.19(m,5H),5.18-5.13(m,0.6H),5.04-4.99(m,0.4H) ,3.74-3.67(m,1H),3.60(s,1.7H),3.46(s,1.3H),2.61-2.52(m,1H),2.17-2.06(m, 1H),1.79-1.63(m,2H),1.57-1.40(m,2H),1.21(d,J=7.5Hz,12H),0.80-0.73(m,2H). 13C NMR (101MHz, CDCl3) δ174.37,173.96,166.23,166.07,139.07,138.72,132 .96,132.87,130.66,130.58,129.79,129.73,128.90,128.85,128.42,128. 36,128.07,127.86,127.57,127.46,83.10,83.09,73.25,73.16,52.23,52.08,48.49,48.01,37.89,37.83,37.31,37.03,24.93,24.91,19.59,19.50.

[0068] Example 6: Synthesis of 6-methoxy-5-(3-methoxyphenyl)-6-oxo-1-phenylhexan-3-yl benzoate (3f)

[0069]

[0070] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and the mixture was stirred at 25 °C for 10 min. Then, phenylpropionaldehyde (27 μL, 0.2 mmol) was added, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ to obtain the alkyl bromide product, which could be used directly in the next step without further purification. The reaction flask containing the alkyl bromide product was placed in a glove box, and Acid Red 94 (2.0 mg, 0.01 mmol), K₃PO₄ (126 mg, 0.6 mmol), and 5A molecular sieve (100 mg) were added. The reaction mixture was then removed from the glove box and subjected to three CO2 purgings in a double-row tube. Under a CO2 atmosphere, DMA (2 mL, 0.1 M), 1-methoxy-3-vinylbenzene (81 μL, 0.6 mmol), and TMEDA (90 μL, 0.6 mmol) were added sequentially. The mixture was stirred for 12 hours at 25 °C under blue LEDs (390 nm). After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. 2 mL of diethyl ether and 0.5 mL of methanol were added, and the mixture was placed at 0 °C. 2 MTCMSCH2N2 (200 μL, 0.4 mmol) was slowly added dropwise, and the mixture was stirred at this temperature for 0.5 h. The solvent was evaporated to dryness, and the residue was purified by rapid chromatography. The yield of 6-methoxy-5-(3-methoxyphenyl)-6-oxo-1-phenylhexane-3-ylbenzoate was 61%. 1 H NMR (400MHz, CDCl3) δ7.97-7.90(m,2H),7.52-7.47(m,1H),7.40-7.34(m,2H),7.20-7.03(m,6H),6.79-6.65(m,3H),5.21 -5.16(m,0.7H),5.05-4.99(m,0.3H),3.68-3.59(m,4H),3.53(s,2H),3.41(s,1H),2.69-2.47(m,3H),2.14-1.82(m,3H). 13C NMR (101MHz, CDCl3) δ174.10,173.74,166.23,166.08,159.97,159.94,141.44,141.33,140.3 9,140.01,133.10,133.01,130.38,130.34,129.90,129.85,129.76,129.70,128.53,128.50,1 28.41,128.40,128.36,126.06,126.04,120.34,120.14,113.66,113.59,113.22,112.90,72.93,72.71,55.28,55.26,52.27,52.13,48.39,48.07,38.12,37.96,36.52,36.43,31.70,31.55.

[0071] Example 7: Synthesis of 5-(4-chlorophenyl)-6-methoxy-6-oxo-1-phenylhexan-3-yl benzoate (3g)

[0072]

[0073] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and the mixture was stirred at 25 °C for 10 min. Then, phenylpropionaldehyde (27 μL, 0.2 mmol) was added, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ to obtain the alkyl bromide product, which could be used directly in the next step without further purification. The reaction flask containing the alkyl bromide product was placed in a glove box, and 3DPAFIPN (1.5 mg, 0.01 mmol), t-BuOK (67 mg, 0.6 mmol), and 5A molecular sieve (100 mg) were added. The reaction mixture was then removed from the glove box and subjected to three CO2 purgings in a double-row tube. Under a CO2 atmosphere, THF (2 mL, 0.1 M), 4-chlorostyrene (23 μL, 0.2 mmol), and DIPEA (104 μL, 0.6 mmol) were added sequentially. The mixture was stirred for 12 hours at 25 °C under blue LEDs (455 nm). After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. 2 mL of diethyl ether and 0.5 mL of methanol were added, and the mixture was placed at 0 °C. 2 M TMSCH2N2 (200 μL, 0.4 mmol) was slowly added dropwise, and the mixture was stirred at this temperature for 0.5 h. The solvent was evaporated to dryness, and the residue was purified by rapid chromatography. The yield of 5-(4-chlorophenyl)-6-methoxy-6-oxo-1-phenylhexane-3-ylbenzoate was 80%. 1 H NMR(500MHz, CDCl3)δ7.94(d,J=8.5Hz,0.7H),7.87(d,J=8.5Hz,1.3H),7.52-7.47(m,1H),7.40-7.34(m,2H),7.20-7.02(m,9H),5 .17-5.12(m,0.7H),5.00-4.95(m,0.3H),3.62-3.59(m,1H),3.52(s,1.9H),3.41(s,1.1H),2.67-2.43(m,3H),2.11-1.82(m,3H). 13C NMR (101MHz, CDCl3) δ173.87,173.52,166.23,166.10,141.34,141.18,137.27,1 36.96,133.60,133.45,133.21,133.12,130.24,130.21,129.77,129.67,129.49 ,129.24,129.12,129.03,128.58,128.55,128.46,128.41,128.37,126.13,72.78,72.43,52.38,52.25,47.71,47.60,38.02,37.95,36.47,36.41,31.70,31.58.

[0074] Example 8: Synthesis of 5-(dibenzo[b,d]furan-3-yl)-6-methoxy-6-oxo-1-phenylhexan-3-yl benzoate (3h)

[0075]

[0076] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and the mixture was stirred at 25 °C for 10 min. Then, phenylpropionaldehyde (27 μL, 0.2 mmol) was added, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ to obtain the alkyl bromide product, which could be used directly in the next step without further purification. The reaction flask containing the alkyl bromide product was placed in a glove box, and Acid Red 94 (2.0 mg, 0.01 mmol), K₃PO₄ (126 mg, 0.6 mmol), and 5A molecular sieve (100 mg) were added. The reaction mixture was then removed from the glove box and subjected to three CO2 purgings in a double-row tube. Acetonitrile (2 mL, 0.1 M), 3-vinyldibenzofuran (116 mg, 0.6 mmol), and TMEDA (30 μL, 0.2 mmol) were added sequentially under a CO2 atmosphere. The mixture was stirred for 12 hours at 25°C under blue LEDs (455 nm). After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. 2 mL of diethyl ether and 0.5 mL of methanol were added, and the mixture was placed at 0°C. 2 MTCMSCH2N2 (46 μL, 0.31 mmol) was slowly added dropwise, and the mixture was stirred at this temperature for 0.5 h. The solvent was then evaporated to dryness, and the residue was purified by rapid chromatography. The yield of 5-(dibenzo[b,d]furan-3-yl)-6-methoxy-6-oxo-1-phenylhexane-3-ylbenzoate was 76%. 1 HNMR(400MHz, CDCl3)δ7.96-7.93(m,0.7H),7.85-7.70(m,3.3H),7.47-6.99(m,13H),5.24-5.18(m,0.6H),5.06-5.00 (m,0.4H),3.82-3.78(m,1H),3.53(s,1.9H),3.41(s,1.1H),2.69-2.53(m,3H),2.24-2.13(m,1H),2.06-1.82(m,2H). 13C NMR (101MHz, CDCl3) δ174.07,173.73,166.23,166.12,156.62,156.58,156.52,141.40,141.24,138.27,137.96,1 33.11,132.91,130.28,130.20,129.76,129.60,128.55,128.50,128.48,128.41,128.36,128.30,127.28,127.22 ,126.09,126.06,124.04,123.99,123.82,123.66,122.95,122.88,122.82,122.65,120.96,120.89,120.72,120.66,111.77,111.73,111.25,111.12,72.91,72.64,52.38,52.25,48.60,48.54,38.36,38.24,36.52,31.71,31.60.

[0077] Example 9: Synthesis of 6-methoxy-5-methyl-6-oxo-1,5-diphenylhexan-3-yl benzoate (3i)

[0078]

[0079] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and the mixture was stirred at 25 °C for 10 min. Then, phenylpropionaldehyde (27 μL, 0.2 mmol) was added, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ to obtain the alkyl bromide product, which could be used directly in the next step without further purification. The reaction flask containing the alkyl bromide product was placed in a glove box, and Acid Red 94 (2.0 mg, 0.01 mmol), K₃PO₄ (126 mg, 0.6 mmol), and 5A molecular sieve (100 mg) were added. The reaction mixture was then removed from the glove box and subjected to three CO2 purgings in a double-row tube. DMA (2 mL, 0.1 M), 1-methyl-1-phenylethylene (26 μL, 0.2 mmol), and TMEDA (90 μL, 0.6 mmol) were added sequentially under a CO2 atmosphere. The mixture was stirred for 12 hours at 25 °C under blue LEDs (455 nm) irradiation. After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. 2 mL of diethyl ether and 0.5 mL of methanol were added, and the mixture was placed at 0 °C. 2 MtMSCH2N2 (200 μL, 0.4 mmol) was slowly added dropwise, and the mixture was stirred at this temperature for 0.5 h. The solvent was evaporated to dryness, and the residue was purified by rapid chromatography. The yield of 6-methoxy-5-methyl-6-oxo-1,5-diphenylhexyl-3-ylbenzoate was 47%. 1 H NMR(400MHz, CDCl3) δ7.92(d,J=6.8Hz,0.8H),7.69(d,J=8.8Hz,1.2H),7.50-6.94(m,13H),5.31-5.1 4(m,1H),3.56(s,1.7H),3.40(s,1.3H),2.68-2.20(m,4H),1.98-1.72(m,2H),1.56(d,J=4.4Hz,3H). 13C NMR (101MHz, CDCl3) δ176.53,176.40,166.01,165.92,143.28,141.58,141.47,13 3.06,132.84,130.45,130.30,129.79,129.64,128.72,128.56,128.51,128.50,1 28.42,128.39,128.18,127.15,126.83,126.05,126.02,125.82,71.86,71.49,52.48,52.34,49.47,48.89,43.85,43.53,37.78,37.61,31.46,31.41,22.30,21.94.

[0080] Example 10: Synthesis of 5-(1-benzoyl-1H-indol-5-yl)-6-methoxy-6-oxo-1-phenylhexan-3-ylbenzoate (3j)

[0081]

[0082] Zinc bromide (4.5 mg, 0.02 mmol) was accurately weighed into a glove box, followed by the addition of DCM (0.2 mL) and benzoyl bromide (25 μL, 0.21 mmol), and the mixture was stirred at 25 °C for 10 min. Then, phenylpropionaldehyde (27 μL, 0.2 mmol) was added, and the mixture was stirred at 25 °C for 2 h. After the reaction was complete, the mixture was filtered through neutral Al₂O₃ to obtain the alkyl bromide product, which could be used directly in the next step without further purification. The reaction flask containing the alkyl bromide product was placed in a glove box, and 3DPAFIPN (1.5 mg, 0.01 mmol), K₃PO₄ (126 mg, 0.6 mmol), and 5A molecular sieve (100 mg) were added. The reaction mixture was then removed from the glove box and subjected to three CO2 purgings in a double-row tube. Acetone (2 mL, 0.1 M), phenyl(5-vinyl-1H-indol-1-yl) methyl ketone (23 μL, 0.2 mmol), and TMEDA (30 μL, 0.2 mmol) were added sequentially under a CO2 atmosphere. The mixture was stirred for 24 hours at -10°C under blue LEDs (455 nm) irradiation. After the reaction was complete, the reaction mixture was diluted with 2 mL of EA and acidified with 2 mL of 2 M HCl for 15 min. The organic layer was then extracted with EA, dried over Na2SO4, filtered, and concentrated under reduced pressure. 2 mL of diethyl ether and 0.5 mL of methanol were added, and the mixture was placed at 0°C. 2 M TMSCH2N2 (200 μL, 0.4 mmol) was slowly added dropwise, and the mixture was stirred at this temperature for 0.5 h. The solvent was then evaporated to dryness, and the residue was purified by rapid chromatography. The yield of 5-(1-benzoyl-1H-indol-5-yl)-6-methoxy-6-oxo-1-phenylhexane-3-ylbenzoate was 48%. 1 H NMR (400MHz, CDCl3) δ8.23(d,J=8.8Hz,0.4H),8.18(d,J=8.4Hz,0.6H),7.95(d,J=6.8H z,0.8H),7.87(d,J=8.0Hz,1.2H),7.63-7.59(m,2H),7.52-7.29(m,7H),7.22-7.01(m,7 H),6.45(q,J=4.4Hz,1H),5.24-5.18(m,0.6H),5.05-4.99(m,0.4H),3.79-3.74(m,1H), 3.53(s,1.8H),3.41(s,1.2H),2.66-2.53(m,3H),2.24-2.11(m,1H),1.98-1.82(m,2H). 13C NMR(101MHz,CDCl3)δ174.45,174.09,168.61,168.54,166.22,166.10,141.45,141.32,135.48,135.35,134.60,134.53,134.50,134.20,133.09,132.93,132.04,131.33,131.28,130.31,130.27,129.75,129.63,129.23,129.21,128.71,128.53,128.49,128.46,128.40,128.36,128.31,128.21,128.17,126.05,126.03,124.92,124.75,120.33,120.02,116.81,116.75,108.63,108.54,72.96,72.71,52.29,52.16,48.22,48.12,38.40,38.15,36.52,36.49,31.69,31.57.

Claims

1. A method for preparing a photocatalytic γ-hydroxycarboxylic acid compound, characterized in that, The synthetic route using alkyl aldehydes, olefins, and CO2 as raw materials is as follows: ； ； R 1 It is a phenylethyl, hydrogen, or alkyl borate ester; R 2 It is methoxy, chlorine, benzofuran, methyl, and imidazole; The steps are as follows: (1) Dissolve alkyl aldehyde (1), benzoyl bromide and zinc bromide in dichloromethane, stir at room temperature for 2 hours, filter, and evaporate the solvent to generate ester bromide (1') in situ by one-pot method. (2) Photocatalyst, base, and 5A molecular sieve are added to the in-situ generated ester bromide (1'). After adding solvent, XAT reagent and olefin (2) under CO2 atmosphere, the reaction is irradiated under blue light to synthesize γ-hydroxycarboxylic acid compounds (3).

2. The method for preparing the photocatalytic γ-hydroxycarboxylic acid compound according to claim 1, characterized in that, In step (1), The concentration of alkyl aldehyde in the reaction system is 0.1 M; The molar ratio of alkyl aldehyde, benzoyl bromide, and zinc bromide is 1:1.05:1; Neutral alumina is used for filtration.

3. The method for preparing the photocatalytic γ-hydroxycarboxylic acid compound according to claim 1, characterized in that, In step (2), The solvent is selected from toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetone, and acetonitrile; The photocatalysts were selected from 3DPAFIPN, 4CzIPN, sodium fluorescein, and Acid Red 94; XAT reagents are selected from TMEDA, DIPEA and (TMS)3SiH; The base is selected from K3PO4 and Na2CO. 3、 Cs2CO3, t-BuOK.

4. The method for preparing the photocatalytic γ-hydroxycarboxylic acid compound according to claim 1, characterized in that, In step (2), The molar ratio of alkyl aldehydes to alkenes is 1:1 to 1:3; The molar ratio of alkyl aldehyde to photocatalyst is 1:0.01; The molar ratio of alkyl aldehyde to XAT reagent is 1:1 to 1:3; The molar ratio of alkyl aldehyde to base is 1:1 to 1:3; The concentration of 5A molecular sieve in solution is 50 mg / mL.

5. The method for preparing the photocatalytic γ-hydroxycarboxylic acid compound according to claim 1, characterized in that, In step (2), The reaction time was 12 h to 24 h, the reaction temperature was -10 ℃ to 25 ℃, and the blue light wavelength of the reaction was 390 nm to 456 nm.

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