Preparation method of photocatalytic gamma-hydroxy carboxylic acid compound

Abstract

The invention belongs to the technical field of organic chemical synthesis, and discloses a preparation method of a photocatalytic gamma-hydroxy carboxylic acid compound, which is characterized in that alkyl aldehyde, olefin and CO2 are used as raw materials, 3DPAFIPN is used as a photocatalyst, TMEDA is used as an XAT reagent, and a series of gamma-hydroxy carboxylic acid compounds are prepared by a one-pot method under illumination. According to the method, the mode of synthesizing the gamma-hydroxycarboxylic acid by three-component carboxylation reaction of the photocatalytic fatty aldehyde, CO2 and olefin is realized for the first time, and the blank in the prior art is filled. The method provided by the invention has the advantages of mild process conditions, short flow, simple steps and wide substrate applicability, and meets the requirements of industrial production; research finds that the yield of the product can reach 77%, and the generated gamma-hydroxy carboxylic acid compound has wide application prospects in organic synthesis and drug research and development. Therefore, the method has important application value.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemical synthesis, and relates to preparing a series of gamma-hydroxycarboxylic acid compounds by reacting cheap and readily available alkyl aldehydes with olefins and CO2 under visible light induction. Background Art

[0002] γ-Hydroxycarboxylic acid derivatives are widely present in natural products, bioactive molecules and drug molecules, such as fluoxetine, ezetimibe tablets, eldanolide, stemonamide, etc., which have good effects in anti-depression and lowering plasma cholesterol. In addition, hydroxycarboxylic acid is also one of the common functional groups in organic chemistry and plays an important role in the field of synthetic chemistry. Therefore, it is of great significance to develop new and efficient synthesis methods for hydroxycarboxylic acid compounds.

[0003] At present, 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 CycloisoMeriz ations 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 Enantioselec tive Synthesis of γ-and δ-Lactones, Org. Lett. 2020, 22, 818-822. (f) Selective Oxidation of 1,3-Butanediol to 3-Hydroxybutyric Acid over PtSb2 Alloy, ACS Sustainable Chem. Eng. 2023, 11, 587-596.] The methods are summarized as hydrogenation of γ-ketoacid derivatives, cycloisomerization and hydrolysis of 4-pentynoic acid, dehydrogenative coupling of alcohols and hydroxides, selective oxidation, HMF hydrolysis and hydrogenation, etc.However, the above reaction still has some defects, such as harsh reaction conditions, the need for pre-functionalization, limited substrate range, and expensive catalysts. Therefore, developing a simple reaction system to synthesize γ-hydroxycarboxylic acid derivatives from cheap and readily available raw materials aldehydes and olefins, and reacting them with abundant C1 resources CO2 under visible light catalysis has important research significance and application potential.

[0004] Alkyl aldehydes are a class of abundant raw material chemicals, which are commonly found in simple building blocks, natural products and drug molecules. Alkyl aldehydes are converted into the corresponding α-ester bromides in one step via benzoyl bromide, which can react with XAT reagents to produce alkyl radicals under visible light induction. On the other hand, CO2 is an abundant, ubiquitous, cheap and non-toxic gas in nature. In the past few decades, many useful organic chemicals have been produced using CO2 as a raw material. At present, people are committed to developing technologies to convert CO2 into various high-value-added chemicals. However, CO2 conversion remains a huge challenge. The key problem is that it often requires harsh and demanding reaction conditions due to its high thermodynamic stability and kinetic inertness. Therefore, it is still very important to develop new and efficient catalytic strategies to broaden the range of products using CO2 as a raw material under mild conditions. In addition, olefins are the most common building blocks in organic compounds, and their difunctionalization is one of the most popular research directions in organic synthesis methodology in recent years, with high atom economy and step economy. Therefore, the strategy of converting alkyl aldehydes into alkyl radicals in a one-pot manner through the XAT process under photocatalysis, which are then captured by olefins and then reduced to carbon anions via photocatalytic reduction, which undergo nucleophilic addition to CO2 to generate γ-hydroxycarboxylic acids, not only achieves the difunctionalization of olefins, but also realizes the conversion of CO2. It is a synthetic method with important research significance.

[0005] The present invention uses cheap and readily available alkyl aldehydes as raw materials, and converts them into stable alkyl bromides in one step with benzoyl bromide without complicated post-treatment. Under the catalysis of cheap and readily available organic photocatalyst 3DPAFIPN, the one-pot method is excited by visible light, and reacts with TMEDA to generate alkyl free radicals in an XAT process, which then reacts with olefins and CO2 to generate a series of γ-hydroxycarboxylic acid derivatives. Compared with traditional synthesis methods, visible light, as a green energy source, has milder reaction conditions and better functional group compatibility, thus providing a new idea for the green and efficient synthesis of γ-hydroxycarboxylic acid compounds. Summary of the invention

[0006] The present invention provides a novel synthesis method for preparing γ-hydroxycarboxylic acid by using 3DPAFIPN which is easy to synthesize as a photocatalyst and TMEDA which is cheap and easily available as an XAT reagent to promote the carboxylation reaction of aldehyde with olefin and CO2 under light excitation. The method has the advantages of convenient experimental operation, good substrate compatibility, cheap and easily available raw materials, etc., so the present invention has great application value and social and economic benefits.

[0007] The technical solution of the present invention:

[0008] A method for preparing a photocatalytic γ-hydroxycarboxylic acid compound, using alkyl aldehyde, olefin, CO2 as raw materials, 3DPAFIPN as a photocatalyst, TMEDA as a XAT reagent, and preparing a series of γ-hydroxycarboxylic acid compounds in one pot under light irradiation; the synthesis route is as follows:

[0009]

[0010] R of alkyl aldehyde 1 is phenethyl, substituted phenethyl, hydrogen, alkyl borate;

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

[0012] Here are the steps:

[0013] (1) dissolving an alkyl aldehyde (1), benzoyl bromide and zinc bromide in dichloromethane, stirring at room temperature for 2 hours, filtering, and spinning the solvent to generate an ester bromide (1') in situ by a one-pot method;

[0014] (2) A photocatalyst, a base, and a 5A molecular sieve are added to the in situ generated ester bromide (1'), and a solvent, an XAT (halogen atom transfer) reagent, and an olefin (2) are added under a CO2 atmosphere, and the reaction is irradiated under blue light to synthesize a γ-hydroxycarboxylic acid compound (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 photocatalyst is selected from 3DPAFIPN, 4CzIPN, sodium fluorescein and acid red 94;

[0017] The XAT reagent is selected from TMEDA, DIPEA and (TMS)3SiH;

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

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

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

[0021] The molar ratio of alkyl aldehyde to olefin is 1:1 to 1:3;

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

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

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

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

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

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

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

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

[0030] Beneficial effects of the invention: The invention is a method for preparing γ-hydroxycarboxylic acid, which realizes for the first time a method for synthesizing γ-hydroxycarboxylic acid by photocatalytic carboxylation reaction of fatty aldehydes with olefins and CO2, filling the gap in the prior art. The method of the invention has mild process conditions, short process, simple steps, wide substrate applicability, and meets industrial production requirements; research has found that the yield of the product can reach 77%, and the generated γ-hydroxycarboxylic acid compound has broad application prospects in organic synthesis and drug research and development. It can be seen that the invention has important application value. BRIEF DESCRIPTION OF THE DRAWINGS

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

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

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

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

[0043] Fig.13 For compound 3g 1 H-NMR spectrum.

[0044] Fig.14 For compound 3g 13 C-NMR spectrum.

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

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

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

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

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

[0050] Fig. 20 For compound 3j 13C-NMR spectrum. DETAILED DESCRIPTION

[0051] The specific implementation of the present invention is further described below in conjunction with the accompanying drawings and technical solutions.

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

[0053]

[0054] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in a glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and then stir at 25 ° C for 10 min. Then add phenylpropanal (27 μL, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, neutral Al2O3 is filtered and directly used in the next step without further purification. The Schlenk reaction bottle with the alkyl bromide product is placed in a glove box, and 4CzIPN (1.6 mg, 0.01 mmol), K3PO4 (126 mg, 0.6 mmol), and 5A molecular sieves (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add DMA (2mL, 0.1M), styrene (23μL, 0.2mmol), TMEDA (30μL, 0.2mmol) in sequence under CO2 atmosphere, and stir for 12 hours at 25°C under blue LEDs (390nm). After the reaction is completed, dilute the reaction mixture with 2mL EA, and add 2mL 2M HCl to acidify for 15min, then extract and separate the organic layer with EA, dry with Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by flash chromatography. The yield of 4-(benzoyloxy)-2,6-diphenylhexanoic acid is 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] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in the glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and then stir at 25 ° C for 10 min. Then add 4-cyanophenylpropionaldehyde (29 μL, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, filter with neutral Al2O3 to obtain the alkyl bromide product, which can be directly used in the next step without further purification. The reaction bottle with the alkyl bromide product is placed in the glove box, and sodium fluorescein (0.8 mg, 0.01 mmol), t-BuOK (67 mg, 0.6 mmol), and 5A molecular sieves (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add THF (2mL, 0.1M), styrene (69μL, 0.6mmol), TMEDA (30μL, 0.2mmol) in sequence under CO2 atmosphere, and stir for 24 hours at 25°C under blue LEDs (456nm). After the reaction is completed, dilute the reaction mixture with 2mL EA, and add 2mL 2M HCl to acidify for 15min, then extract and separate the organic layer with EA, dry with Na2SO4, filter, and concentrate under reduced pressure. Then add 2mL ether, 0.5mL methanol, place at 0°C, slowly add 2M TMSCH2N2 (200μL, 0.4mmol), stir at this temperature for 0.5h, spin dry the solvent, and purify the residue by flash chromatography. The yield of 1-(4-cyanophenyl)-6-methoxy-6-oxy-5-phenylhexane-3-yl benzoate is 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] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in the glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and then stir at 25 ° C for 10 min. Then add 4-methoxyphenylpropanal (32 mg, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, filter with neutral Al2O3 to obtain the alkyl bromide product, which can be directly used in the next step without further purification. The reaction bottle with the alkyl bromide product is placed in the glove box, and 3DPAFIPN (1.5 mg, 0.01 mmol), Na2CO3 (63 mg, 0.6 mmol), and 5A molecular sieves (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add toluene (2mL, 0.1M), styrene (23μL, 0.2mmol), TMEDA (90μL, 0.6mmol) in sequence under CO2 atmosphere, and place the reactor at -78℃ for 2min under CO2 atmosphere. Then the resulting mixture is restored to room temperature, irradiated with blue LEDs (455nm) and stirred for 12 hours at -10℃. After the reaction is completed, the reaction mixture is diluted with 2mL EA, and 2mL 2M HCl is added to acidify for 15min, then the organic layer is separated by extraction with EA, dried with Na2SO4, filtered, and concentrated under reduced pressure. Then 2mL ether and 0.5mL methanol are added, placed at 0℃, 2M TMSCH2N2 (200μL, 0.4mmol) is slowly added dropwise, stirred at this temperature for 0.5h, the solvent is spin-dried, and the residue is purified by flash chromatography. The yield of 6-methoxy-1-(4-methoxyphenyl)-6-oxo-5-phenylhexan-3-yl benzoate 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] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in the glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and then stir at 25 ° C for 10 min. Then add acetaldehyde (11 μL, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, filter with neutral Al2O3 to obtain the alkyl bromide product, which can be directly used in the next step without further purification. The reaction bottle with the alkyl bromide product is placed in the glove box, and 3DPAFIPN (1.5 mg, 0.01 mmol), K3PO4 (42 mg, 0.2 mmol), and 5A molecular sieves (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add DMSO (2mL, 0.1M), styrene (23μL, 0.2mmol), TMEDA (30μL, 0.2mmol) in sequence under CO2 atmosphere, and stir for 24 hours at 25°C under blue LEDs (440nm). After the reaction is completed, dilute the reaction mixture with 2mL EA, and add 2mL 2M HCl to acidify for 15min, then extract and separate the organic layer with EA, dry with Na2SO4, filter, and concentrate under reduced pressure. Then add 2mL ether, 0.5mL methanol, place at 0°C, slowly add 2M TMSCH2N2 (200μL, 0.4mmol), stir at this temperature for 0.5h, spin dry the solvent, and purify the residue by flash chromatography. The yield of 5-methoxy-5-oxy-4-phenylpentyl-2-yl benzoate is 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-dioxaborolan-2-yl)heptane-4-yl benzoate

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

[0066]

[0067] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in the glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and stir at 25 ° C for 10 min. Then add 4-(4,4,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyraldehyde (44 uμL, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, filter with neutral Al2O3 to obtain the alkyl bromide product, which can be directly used in the next step without further purification. The reaction bottle with the alkyl bromide product is placed in the glove box, and 3DPAFIPN (6.5 mg, 0.01 mmol), K3PO4 (42 mg, 0.2 mmol), and 5A molecular sieves (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add toluene (2mL, 0.1M), styrene (23μL, 0.2mmol), (TMS)3SiH (54mg, 0.6mmol) in sequence under CO2 atmosphere, and place the reactor at -78°C for 2min under CO2 atmosphere. Then the resulting mixture is restored to room temperature, irradiated with blue LEDs (455nm) and stirred for 12 hours at 25°C. After the reaction is completed, the reaction mixture is diluted with 2mL EA, and 2mL 2M HCl is added to acidify for 15min, then the organic layer is separated by extraction with EA, dried with Na2SO4, filtered, and concentrated under reduced pressure. Then 2mL ether and 0.5mL methanol are added, placed at 0°C, 2M TMSCH2N2 (200μL, 0.4mmol) is slowly added dropwise, stirred at this temperature for 0.5h, the solvent is spin-dried, and the residue is purified by flash chromatography. The yield of 1-methoxy-1-oxo-2-phenyl-7-(4,4,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptane-4-yl benzoate 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] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in the glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and then stir at 25 ° C for 10 min. Then add phenylpropanal (27 μL, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, filter with neutral Al2O3 to obtain the alkyl bromide product, which can be directly used in the next step without further purification. The reaction bottle with the alkyl bromide product is placed in the glove box, and acid red 94 (2.0 mg, 0.01 mmol), K3PO4 (126 mg, 0.6 mmol), and 5A molecular sieve (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add DMA (2mL, 0.1M), 1-methoxy-3-vinylbenzene (81μL, 0.6mmol), TMEDA (90μL, 0.6mmol) in sequence under CO2 atmosphere, and stir for 12 hours at 25°C under blue LEDs (390nm). After the reaction is completed, dilute the reaction mixture with 2mL EA, and add 2mL 2M HCl to acidify for 15min, then extract and separate the organic layer with EA, dry with Na2SO4, filter, and concentrate under reduced pressure. Then add 2mL ether, 0.5mL methanol, place at 0°C, slowly add 2MTMSCH2N2 (200μL, 0.4mmol), stir at this temperature for 0.5h, spin dry the solvent, and purify the residue by flash chromatography. The yield of 6-methoxy-5-(3-methoxyphenyl)-6-oxo-1-phenylhexane-3-yl benzoate is 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 (3 g)

[0072]

[0073] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in the glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and then stir at 25 ° C for 10 min. Then add phenylpropanal (27 μL, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, filter with neutral Al2O3 to obtain the alkyl bromide product, which can be directly used in the next step without further purification. The reaction bottle with the alkyl bromide product is placed in the glove box, and 3DPAFIPN (1.5 mg, 0.01 mmol), t-BuOK (67 mg, 0.6 mmol), and 5A molecular sieves (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add THF (2mL, 0.1M), 4-chlorostyrene (23μL, 0.2mmol), DIPEA (104μL, 0.6mmol) in sequence under CO2 atmosphere, and stir for 12 hours at 25°C under blue LEDs (455nm). After the reaction is completed, dilute the reaction mixture with 2mLEA, and add 2mL 2M HCl to acidify for 15min, then extract and separate the organic layer with EA, dry with Na2SO4, filter, and concentrate under reduced pressure. Then add 2mL ether, 0.5mL methanol, place at 0°C, slowly add 2M TMSCH2N2 (200μL, 0.4mmol), stir at this temperature for 0.5h, spin dry the solvent, and purify the residue by flash chromatography. The yield of 5-(4-chlorophenyl)-6-methoxy-6-oxo-1-phenylhexane-3-yl benzoate is 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] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in the glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and then stir at 25 ° C for 10 min. Then add phenylpropanal (27 μL, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, filter with neutral Al2O3 to obtain the alkyl bromide product, which can be directly used in the next step without further purification. The reaction bottle with the alkyl bromide product is placed in the glove box, and acid red 94 (2.0 mg, 0.01 mmol), K3PO4 (126 mg, 0.6 mmol), and 5A molecular sieve (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add acetonitrile (2mL, 0.1M), 3-vinyl dibenzofuran (116mg, 0.6mmol), TMEDA (30μL, 0.2mmol) in sequence under CO2 atmosphere, and stir for 12 hours at 25°C under blue LEDs (455nm). After the reaction is completed, dilute the reaction mixture with 2mL EA, add 2mL 2M HCl to acidify for 15min, then extract and separate the organic layer with EA, dry with Na2SO4, filter, and concentrate under reduced pressure. Then add 2mL ether and 0.5mL methanol, place at 0°C, slowly add 2MTMSCH2N2 (46μL, 0.31mmol), stir at this temperature for 0.5h, spin dry the solvent, and purify the residue by flash chromatography. The yield of 5-(dibenzo[b,d]furan-3-yl)-6-methoxy-6-oxo-1-phenylhexan-3-yl benzoate 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] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in the glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and then stir at 25 ° C for 10 min. Then add phenylpropanal (27 μL, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, filter with neutral Al2O3 to obtain the alkyl bromide product, which can be directly used in the next step without further purification. The reaction bottle with the alkyl bromide product is placed in the glove box, and acid red 94 (2.0 mg, 0.01 mmol), K3PO4 (126 mg, 0.6 mmol), and 5A molecular sieve (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add DMA (2mL, 0.1M), 1-methyl-1-phenylethylene (26μL, 0.2mmol), TMEDA (90μL, 0.6mmol) in sequence under CO2 atmosphere, and stir for 12 hours at 25°C under blue LEDs (455nm). After the reaction is completed, dilute the reaction mixture with 2mL EA, and add 2mL 2M HCl to acidify for 15min, then extract and separate the organic layer with EA, dry with Na2SO4, filter, and concentrate under reduced pressure. Then add 2mL ether, 0.5mL methanol, place at 0°C, slowly add 2MTMSCH2N2 (200μL, 0.4mmol), stir at this temperature for 0.5h, spin dry the solvent, and purify the residue by flash chromatography. The yield of 6-methoxy-5-methyl-6-oxo-1,5-diphenylhexan-3-yl benzoate is 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] Accurately weigh zinc bromide (4.5 mg, 0.02 mmol) in the glove box, then add DCM (0.2 mL), benzoyl bromide (25 μL, 0.21 mmol), and then stir at 25 ° C for 10 min. Then add phenylpropanal (27 μL, 0.2 mmol) to the system, and the system is stirred at 25 ° C for 2 h. After the reaction is completed, filter with neutral Al2O3 to obtain the alkyl bromide product, which can be directly used in the next step without further purification. The reaction bottle with the alkyl bromide product is placed in the glove box, and 3DPAFIPN (1.5 mg, 0.01 mmol), K3PO4 (126 mg, 0.6 mmol), and 5A molecular sieves (100 mg) are added. Then take out the glove box, perform three CO2 replacements on the double-row tube, then add acetone (2mL, 0.1M), phenyl (5-vinyl-1H-indol-1-yl) ketone (23μL, 0.2mmol), TMEDA (30μL, 0.2mmol) in sequence under CO2 atmosphere, and stir for 24 hours at -10°C under blue LEDs (455nm). After the reaction is completed, dilute the reaction mixture with 2mL EA, add 2mL 2M HCl to acidify for 15min, then extract and separate the organic layer with EA, dry with Na2SO4, filter, and concentrate under reduced pressure. Then add 2mL ether and 0.5mL methanol, place at 0°C, slowly add 2M TMSCH2N2 (200μL, 0.4mmol), stir at this temperature for 0.5h, spin dry the solvent, and purify the residue by flash chromatography. The yield of 5-(1-benzoyl-1H-indol-5-yl)-6-methoxy-6-oxo-1-phenylhexan-3-yl benzoate 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: A series of γ-hydroxycarboxylic acid compounds were prepared in one pot using alkyl aldehydes, olefins, and CO2 as raw materials, 3DPAFIPN as a photocatalyst, and TMEDA as an XAT reagent under illumination. The synthetic route is as follows: R of alkyl aldehyde 1 is phenethyl, substituted phenethyl, hydrogen, alkyl borate; R of olefin 2 It is methoxy, chlorine, benzofuran, methyl, imidazole; Here are the steps: (1) Dissolving alkyl aldehyde (1), benzoyl bromide and zinc bromide in dichloromethane, stirring at room temperature for 2 hours, filtering, and then spinning the solvent to generate ester bromide (1') in situ through a one-pot process; (2) A photocatalyst, a base, and a 5A molecular sieve are added to the in situ generated ester bromide (1'), and a solvent, an XAT (halogen atom transfer) reagent, and an olefin (2) are added under a CO2 atmosphere. The reaction is then irradiated under blue light to synthesize a γ-hydroxycarboxylic acid compound (3).

2. The method for preparing a photocatalytic γ-hydroxycarboxylic acid compound according to claim 1, wherein: 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; Filtration was performed using neutral alumina.

3. The method for preparing a photocatalytic γ-hydroxycarboxylic acid compound according to claim 1, wherein: In step (2), The solvent is selected from the group consisting of toluene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetone and acetonitrile; The photocatalyst is selected from 3DPAFIPN, 4CzIPN, sodium fluorescein and acid red 94; The XAT reagent is selected from TMEDA, DIPEA and (TMS)3SiH; Base is selected from K3PO4, Na2CO 3、 Cs2CO3, t-BuOK.

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

5. The method for preparing a photocatalytic γ-hydroxycarboxylic acid compound according to claim 1, wherein: In step (2), The reaction time is 12 hours to 24 hours, the reaction temperature is -10°C to 25°C, and the wavelength of the blue light is 390nm to 456nm.

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