A method for synthesizing alpha-hydroxycarboxylic acid compounds

Abstract

This invention discloses a method for synthesizing α-hydroxycarboxylic acid compounds. The method includes the following steps: adding a reaction substrate, a photosensitizer, and a base to a dry reaction tube; then adding a solvent and additives under a CO2 atmosphere; and reacting under visible light irradiation. After the reaction is complete, the reaction system is acidified and quenched, and then purified to obtain the product, the α-hydroxycarboxylic acid compound. The photosensitizer includes Ir(ppy)2(dtbbpy)PF6 and 3DPA2FBN; the base is potassium tert-butoxide, cesium carbonate, or potassium tert-valerate; the additives are N,N-diisopropylethylamine and chlorosilane; and the reaction substrate is an aldehyde or ketone compound. This invention provides a highly efficient and selective synthesis of α-hydroxycarboxylic acid compounds under visible light induction and a CO2 atmosphere. The reaction conditions of this invention are mild, the reactant range is broad, the selectivity is good, and it can be scaled up to the gram scale.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing α-hydroxycarboxylic acid compounds. Background Technology

[0002] Alpha-hydroxycarboxylic acids (AHAs) are common structural units in bioactive compounds and play a significant role in the cosmetics industry. Furthermore, due to their strong acidity and water solubility, they have numerous applications in organic synthesis: they can serve as chiral ligands, solvents, and building blocks for total synthesis. Finally, they are also common monomers and building blocks of non-natural peptides in polymerization reactions. Therefore, many synthetic strategies have been developed to synthesize these compounds.

[0003] Currently, the most commonly used synthetic methods fall into four categories: first, preparation from α-amino acids via diazotization and hydrolysis; second, nucleophilic addition of hydrogen cyanide (salt) or tribromomethane to aldehydes, followed by hydrolysis; third, selective reduction of prochiral α-keto acids to obtain α-hydroxycarboxylic acids; and fourth, selective oxidation of 1,2-diols to prepare α-hydroxycarboxylic acid analogs. Other methods exist, such as nucleophilic addition with glycidic acid or glyoxylic acid, palladium-catalyzed CH functionalization of lactic acid derivatives, and direct α-CH carboxylation of primary alcohols. However, many of these methods suffer from low yields or limited availability of raw materials, and some even require harsh reaction conditions, necessitating multi-step transformations or dependence on highly toxic and hazardous chemicals like cyanide. Therefore, traditional synthetic methods have certain limitations. Researching novel and efficient methods for synthesizing α-hydroxycarboxylic acid compounds is of great significance, such as synthesizing α-hydroxycarboxylic acid compounds through nucleophilic attack on CO2 using a polarity reversal strategy for aldehyde and ketone carbonyl compounds. This strategy utilizes readily available raw materials and leverages CO2, a greenhouse gas, aligning with the principles of green chemistry. Furthermore, applying clean energy sources like light sources to the synthesis of α-hydroxycarboxylic acid compounds would undoubtedly further enhance the synthetic principles of green chemistry.

[0004] The massive emission of CO2 has led to global warming, rising sea levels, ecological degradation, and frequent natural disasters. Therefore, it is crucial to conduct fundamental research on CO2 emission reduction and rational utilization. Achieving efficient conversion of CO2 into valuable carboxylic acid molecules and realizing large-scale industrial production would not only create new industrial models for chemical production and reduce production costs, but also significantly improve the utilization efficiency of CO2 resources, providing a new approach to addressing the greenhouse effect. Currently, chemists have achieved some CO2 conversions and obtained a series of high-value-added chemicals. However, the chemical utilization of CO2, especially its industrialization, is only the tip of the iceberg, mainly due to the thermodynamic stability and kinetic inertness of CO2. Therefore, exploring efficient and novel CO2 conversion reactions to promote the resource utilization of CO2 and facilitate the global carbon cycle has significant academic and practical value. Summary of the Invention

[0005] The purpose of this invention is to provide a method for synthesizing α-hydroxycarboxylic acid compounds, which addresses the limitations of existing synthetic techniques. This method has advantages such as high yield, mild reaction conditions, low toxicity of reagents, and low cost.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is: to provide a method for synthesizing α-hydroxycarboxylic acid compounds, characterized by comprising the following steps:

[0007] S1: Add photosensitizer and base to the reaction substrate, then add solvent and additive under CO2 atmosphere, mix well to obtain reaction solution; the reaction substrate is aldehyde or ketone compound, and the additive is a mixture of N,N-diisopropylethylamine and chlorosilane;

[0008] S2: Place the reaction solution obtained in S1 at a distance of 1-5 cm from a visible light source, stir at room temperature for 0.1 h to 48 h, quench the reaction with a quenching agent, and evaporate the solvent to obtain the crude product.

[0009] S3: The crude product obtained from S2 was purified by rapid column chromatography to obtain α-hydroxycarboxylic acid compounds.

[0010] In this paper, the synthetic reaction equations for α-hydroxycarboxylic acid compounds are as follows:

[0011]

[0012] The reaction principle of this invention is as follows: Figure 1As shown, in the photocatalytic system, DIPEA first reduces and quenches the photosensitizer, and then the substrate activated by chlorosilane undergoes a single-electron transfer process with the photosensitizer to generate α-hydroxy carbon radicals. The α-hydroxy carbon radicals are then reduced by a single electron under another catalyst cycle to obtain a carbanion intermediate. This carbanion attacks CO2 to synthesize α-hydroxycarboxylic acid compounds.

[0013] Based on the above technical solution, the present invention can be further improved as follows.

[0014] Furthermore, the structural formula of the reaction substrate is shown in formula (I):

[0015]

[0016] Among them, R 1 It is aryl or alkyl; R 2 It can be hydrogen, alkyl, aryl, ester, or amide.

[0017] Furthermore, the amount of photosensitizer used is 0.1–5 mol% of the reaction substrate; the amount of base added is 1–3 equivalents of the reaction substrate; the amount of N,N-diisopropylethylamine added as an additive is 1–3 equivalents of the reaction substrate, and the amount of chlorosilane added is 1–3 equivalents of the reaction substrate.

[0018] Furthermore, the photosensitizer is an Ir-type photosensitizer or a 3DPA2FBN-type organic dye.

[0019] Furthermore, the base is potassium tert-butoxide, cesium carbonate, or potassium tert-valerate.

[0020] Furthermore, the solvent is DMF or DMA.

[0021] Furthermore, the quenching agent is tetrabutylammonium fluoride or hydrochloric acid aqueous solution.

[0022] Furthermore, the visible light source is a 30W blue LED light.

[0023] Furthermore, the eluent used for column chromatography purification in S3 was a mixture of petroleum ether, ethyl acetate, and glacial acetic acid, with a volume ratio of petroleum ether to ethyl acetate of 10:1 and a mass fraction of glacial acetic acid of 0.1% to 1%.

[0024] The beneficial effects of this invention are: this invention can efficiently synthesize α-hydroxycarboxylic acid compounds under visible light induction; the reaction conditions of this invention are mild, the substrate range is broad, the selectivity is good, and it can be scaled up to the gram scale without significantly affecting the yield, maintaining a high yield; this invention overcomes the shortcomings of existing technologies such as high reagent toxicity and harsh reaction conditions, and the raw materials used are inexpensive and readily available. Attached Figure Description

[0025] Figure 1This is a schematic diagram illustrating the synthesis principle of the α-hydroxycarboxylic acid compounds of this invention. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention; that is, the described embodiments are merely some embodiments of the invention, and not all embodiments.

[0027] Therefore, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0028] It should be noted that relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0029] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0030] Example 1

[0031] A preferred embodiment of the present invention provides a method for synthesizing α-hydroxycarboxylic acid compounds, the specific steps of which are as follows:

[0032]

[0033] S1: Add 1 or 5 (0.2 mmol, 1.0 equivalent), Ir(ppy)2(dtbbpy)PF6 (1.9 mg, 0.002 mmol, 1 mol%) or 3DPA2FBN (2.6 mg, 0.004 mmol, 2 mol%) to a dry Schlenk tube (10 mL);

[0034] S2: Add more tBuOK (44.9 mg or 60.9 mg, 0.4 mmol or 0.5 mmol, 2.0 equivalent or 2.5 equivalent);

[0035] S3: Then, evacuate the vacuum, replace the CO2 3 times, and then add sequentially under a CO2 atmosphere. i Pr2NEt (66 μL, 0.04 mmol, 2.0 equivalent), TMSCl (34 μL, 0.26 mmol, 1.3 equivalent), DMA (2 mL or 4 mL);

[0036] S4: Seal the Schlenk tube, stir the reaction in a water bath, and irradiate it with a 30W blue LED lamp (3cm away, with a cooling fan to keep the reaction temperature at 25-30℃) for 12 hours.

[0037] S5: After the reaction is complete, add 0.5 mL n The reaction was quenched by Bu4NF (1N in THF), stirred for 30 minutes, 2 mL of 2N HCl (aq.) and 2.5 mL of EtOAc were added for dilution, stirred for 10 minutes, and EtOAc was extracted 3 times. The combined organic phases were concentrated in vacuum.

[0038] S6: Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate / AcOH 10 / 1 / 1%).

[0039] Example 2

[0040] A preferred embodiment of the present invention provides a method for synthesizing α-hydroxycarboxylic acid compounds, the specific steps of which are as follows:

[0041]

[0042] S1: Add 3 (0.2 mmol, 1.0 equivalent) and Ir(ppy)2(dtbbpy)PF6 (1.9 mg, 0.002 mmol, 1 mol%) to a dry Schlenk tube (10 mL);

[0043] S2: Add Cs2CO3 (130.0 mg, 0.4 mmol, 2.0 equivalents);

[0044] S3: Then, evacuate the vacuum, replace the CO2 3 times, and then add sequentially under a CO2 atmosphere. i Pr2NEt (33 μL or 50 μL, 0.02 mmol or 0.03 mmol, 1.0 equivalent or 1.5 equivalent), DMF (2 mL);

[0045] S4: Seal the Schlenk tube, stir the reaction in a water bath, and irradiate it with a 30W blue LED lamp (5cm away, with a cooling fan to keep the reaction temperature at 25-30℃) for 48 hours.

[0046] S5: After the reaction was completed, add 2 mL of 2N HCl (aq.) and 2.5 mL of EtOAc to dilute. Stir for 10 minutes, extract with EtOAc 3 times, and concentrate the combined organic phase under vacuum.

[0047] S6: Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate / AcOH 10 / 1 / 0.1%).

[0048] Example 3

[0049] A preferred embodiment of the present invention provides a method for synthesizing α-hydroxycarboxylic acid compounds, the specific steps of which are as follows:

[0050]

[0051] S1: Add 7 (0.2 mmol, 1.0 equivalent) and Ir(ppy)2(dtbbpy)PF6 (1.9 mg, 0.002 mmol, 1 mol%) to a dry Schlenk tube (25 mL);

[0052] S2: Add Ph3SiCl (76.7 mg, 0.26 mmol, 1.3 equivalents) and PivOK (84.1 mg, 0.6 mmol, 3.0 equivalents);

[0053] S3: Then, evacuate the vacuum, replace the CO2 3 times, and then add sequentially under a CO2 atmosphere. i Pr2NEt (66 μL, 0.04 mmol, 2.0 equivalent), DMA (6 mL);

[0054] S4: Seal the Schlenk tube, stir the reaction in a water bath, and irradiate it with a 30W blue LED lamp (1cm away, with a cooling fan to keep the reaction temperature at 25-30℃) for 30 minutes.

[0055] S5: After the reaction is complete, add 0.5 mL n The reaction was quenched by Bu4NF (1N in THF), stirred for 30 minutes, 3 mL of 2N HCl (aq.) and 10 mL of EtOAc were added for dilution, stirred for 10 minutes, and EtOAc was extracted 3 times. The combined organic phases were concentrated in vacuum.

[0056] S6: Add 30 mL of EtOAc to dissolve, wash twice with water, and evaporate the solvent.

[0057] S7: Dissolve in 4 mL MeOH / Et2O (1 / 3), add TMSCHN2 (0.3 mL, 0.6 mmol, 2 M inhexanes) dropwise at 0 °C, and react until esterification is complete.

[0058] S8: Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate 100 / 1-50 / 1).

[0059] Experimental Example

[0060] Based on Example 1, reactions were carried out under different reaction conditions in a CO2 atmosphere at room temperature and one atmosphere. Some of the reaction conditions are shown in Table 1:

[0061] Table 1 shows the reaction conditions and yields for arylalkyl ketones as an example.

[0062]

[0063]

[0064] Note: The values ​​in parentheses in Table 1 are separation yields, and the rest are liquid phase yields using biphenyl as an internal standard; c indicates that the chlorosilane is 1.3 equivalents; d indicates no light; e indicates no photosensitizer; f indicates no light. i Pr2NEt;g indicates an N2 atmosphere.

[0065] The table shows that alkali, visible light, photosensitizers, and additives are involved. i Pr₂NEt and chlorosilanes are both essential for the formation of the target product, α-hydroxycarboxylic acid. This invention successfully achieved the production of the target product in good yield using aldehydes and ketones as raw materials.

[0066] The products and their yields obtained in the embodiments of the present invention are shown below:

[0067] The products and their yields obtained in the embodiments of the present invention are shown below:

[0068]

[0069] a indicates the use of 3DPA2FBN (2.0 mol%) instead of Ir(ppy)2(dtbbpy)PF6; b indicates KO t Bu (2.5 equiv), DMA (4 mL).

[0070]

[0071] a represents i Pr2NEt(1.0equiv).

[0072]

[0073] 'a' indicates that BzCl is used for post-processing.

[0074]

[0075] The structural characterization parameters of the α-hydroxycarboxylic acid compounds synthesized in this invention are as follows:

[0076] 2-([1,1'-biphenyl]-4-yl)-2-hydroxypropionic acid (2a)

[0077] 129.34, 127.81, 127.06, 126.65, 126.26, 75.20, 27.74. HRMS(ESI-): Calculated as C 15 H 13 O3 - [MH] - :241.0870, found 241.0874.

[0078] 2-([1,1'-biphenyl]-4-yl)-2-hydroxybutyric acid (2b)

[0079] MHz, DMSO-d6)δ176.14,142.73,140.27,139.27,129.33,127.80,127.04,126.62,126.57,78.15,32.73,8.62.HRMS(ESI-): calculated as C 16 H 15 O3 - [MH] - :255.1027, found 255.1030.

[0080] 2-([1,1'-biphenyl]-4-yl)-2-hydroxyhexanoic acid (2c)

[0081] 3H). 13 C NMR (101MHz, DMSO-d6) δ 176.53, 143.71, 140.43, 139.00, 129.37, 127.77, 127.06, 126.66, 126.45, 77.91, 26.21, 22.90, 14.49. HRMS (ESI-) calculated as C 18 H 19 O3 - [MH] - :283.1340, found 283.1336.

[0082] 2-([1,1'-biphenyl]-4-yl)-2-hydroxy-3-methylbutyric acid (2d)

[0083] NMR (101MHz, DMSO-d6) δ 176.41, 142.25, 139.09, 129.33, 127.78, 127.02, 126.91, 126.45, 80.55, 35.60, 17.82, 16.43. HRMS (ESI-) calculated as C 17 H 17 O3 - [MH] - :269.1183, found 269.1188.

[0084] 2-([1,1'-biphenyl]-4-yl)-2-hydroxy-3,3-dimethylbutyric acid (2e)

[0085] 140.19, 139.97, 139.02, 129.33, 128.43, 127.79, 126.98, 125.54, 82.05, 38.75, 26.25. HRMS(ESI-) calculated as C 18 H 19 O3 - [MH] - :283.1340, found 283.1343.

[0086] 2-Hydroxy-2-(naphth-2-yl)propionic acid (2f)

[0087] 176.62, 142.83, 132.99, 132.50, 128.48, 127.77, 127.69, 126.51, 126.28, 124.64, 123.98, 75.52, 27.82. HRMS(ESI-) calculated as C 13 H 11 O3 - [MH] - :215.0714, found 215.0718.

[0088] 2-Hydroxy-2-(4-(thiophen-2-yl)phenyl)propionic acid (2g)

[0089] 176.32, 144.13, 143.46, 132.98, 128.90, 126.42, 126.04, 125.40, 124.08, 75.16, 27.65. HRMS(ESI-) calculated as C 13 H11 O3S - [MH] - :247.0434, found 247.0433.

[0090] 2-(4-(tert-butoxycarbonyl)phenyl)-2-hydroxypropionic acid (2h)

[0091]

[0092] 149.86, 130.54, 129.11, 125.89, 81.02, 75.44, 28.25, 27.82. HRMS (ESI-) calculated as C 14 H 17 O5 - [MH] - :265.1081, found 265.1080.

[0093] 2-Cyclohexyl-2-hydroxy-2-phenylacetic acid (2i)

[0094] 2H), 1.15–0.89(m,4H). 13 C NMR (101MHz, DMSO-d6) δ 176.42, 142.53, 128.12, 127.23, 126.28, 80.60, 45.63, 27.57, 26.39, 26.27, 25.82. HRMS (ESI-) calculated as C 14 H 17 O3 - [MH] - :233.1183, found 233.1182.

[0095] 2-Hydroxy-2,3-diphenylpropionic acid (2j)

[0096] 1H),7.20–7.09(m,5H),3.42(d,J=13.7Hz,1H),3.15(d,J=13.7Hz,1H). 13 C NMR (101MHz, DMSO-d6) δ 175.67, 143.34, 137.31, 131.07, 128.15, 127.79, 127.52, 126.45, 126.13, 78.45, 45.40. HRMS (ESI-) calculated as C 15 H 13 O3 - [MH] - :241.0870, found 241.0872.

[0097] 2-Hydroxy-2-phenylpropionic acid (2kJ)

[0098] 75.25, 27.81. HRMS (ESI+) calculation is C9H 10 NaO3 + [M+Na] + :189.0522, found 189.0517.

[0099] 2-Hydroxy-2-(2-methoxyphenyl)propionic acid (2l)

[0100] 128.60, 125.86, 120.45, 111.63, 73.65, 55.81, 25.88. HRMS (ESI+) calculated as C 10 H 12 NaO4 + [M+Na] + :219.0628, found 219.0627.

[0101] 2-Hydroxy-2,2-diphenylacetic acid (4a)

[0102] LRMS(ESI-) is calculated as C 14 H 11 O3 - [MH] - :227.07, found 227.00.

[0103] 2-([1,1'-biphenyl]-4-yl)-2-hydroxy-2-phenylacetic acid (4b)

[0104] 128.14, 127.89, 127.73, 127.49, 127.09, 126.44, 80.55. HRMS(ESI-) calculated as C 20 H 15 O3 - [MH] - :303.1027, found 303.1025.

[0105] 2-Hydroxy-2-phenyl-2-(p-Tolyl)acetic acid (4c)

[0106] 127.57, 127.51, 127.44, 80.53, 21.03. HRMS (ESI-) calculated as C 15 H 13 O3 - [MH]- :241.0870, found 241.0867.

[0107] 2-Hydroxy-2-(4-methoxyphenyl)-2-phenylacetic acid (4d)

[0108] 128.06, 127.59, 127.52, 113.41, 80.34, 55.47. HRMS (ESI-) calculated as C 15 H 13 O4 - [MH] - :257.0819, found 257.0816.

[0109] 2-Hydroxy-2-phenyl-2-(4-(trifluoromethyl)phenyl)acetic acid (4e)

[0110] 128.43,128.35,127.90,128.23(q,J=31.8Hz).127.39,124.75(q,J=272.0Hz),125.00(q,J=3.8Hz),80.54. 19 F NMR (376MHz, DMSO-d6) δ-60.94. HRMS (ESI-) calculated as C 15 H 10 F3O3 - [MH] - :295.0588, found 295.0951.

[0111] 2-(4-Fluorophenyl)-2-hydroxy-2-phenylacetic acid (4f)

[0112] 129.60(d,J=8.3Hz),128.21,127.78,127.37,114.79(d,J=21.3Hz),80.26. 19 F NMR (376MHz, DMSO-d6) δ-115.66.HRMS (ESI-) calculated as C 14 H 10 FO3 - [MH] - :245.0619, found 245.0610.

[0113] 2-(4-Chlorophenyl)-2-hydroxy-2-phenylacetic acid (4g)

[0114] HRMS(ESI-) is calculated as C 14 H10 ClO3 - [MH] - :261.0324, found 261.0321.

[0115] 2-(3-Fluorophenyl)-2-hydroxy-2-phenylacetic acid (4h)

[0116] = 6.8Hz), 143.82, 130.01 (d, J = 8.1Hz), 128.27, 127.84, 127.33, 123.72 (d, J = 2.7Hz), 114.42 (d, J = 20.9Hz), 114.25 (d, J = 22.9Hz), 80.29. 19 F NMR (376MHz, DMSO-d6) δ-113.64.HRMS (ESI-) calculated as C 14 H 10 FO3 - [MH] - :245.0619, found 245.0613.

[0117] 2-(3-Chlorophenyl)-2-hydroxy-2-phenylacetic acid (4i)

[0118] 126.34, 80.33. HRMS(ESI-) calculated as C 14 H 10 ClO3 - [MH] - :261.0324, found 261.0325.

[0119] 2-(2-Fluorophenyl)-2-hydroxy-2-phenylacetic acid (4j)

[0120] MHz, DMSO-d6) δ174.57, 160.65 (d, J = 247.8Hz), 141.65, 132.40 (d, J = 12.7Hz), 130.19 (d, J = 8.5Hz) ,129.34(d,J=3.8Hz),128.17,128.01,127.20,124.00(d,J=3.3Hz),116.08(d,J=22.2Hz),78.15. 19 F NMR (376MHz, DMSO-d6) δ-110.44.HRMS (ESI-) calculated as C 14 H 10 CFO3 - [MH] -:245.0619, found 245.0615.

[0121] 2-Hydroxy-2-phenyl-2-(o-tolyl)acetic acid (4k)

[0122] NMR (101MHz, DMSO-d6) δ 175.65, 142.99, 142.30, 138.04, 132.10, 128.16, 128.10, 127.95, 127.72, 127.36, 125.25, 81.52, 20.92. HRMS (ESI-) calculated as C 15 H 13 FO3 - [MH] - :241.0870, found 241.0872.

[0123] 2,2-Bis(4-fluorophenyl)-2-hydroxyacetic acid (4l)

[0124] NMR (101MHz, DMSO-d6) δ174.84, 161.67 (d, J = 243.4Hz), 140.69 (d, J = 3.0Hz), 129.51 (d, J = 8.2Hz), 114.81 (d, J = 21.3Hz), 79.75. 19 F NMR (376MHz, DMSO-d6) δ-115.63.HRMS (ESI-) calculated as C 14 H9F2O3 - [MH] - :263.0525, found 263.0521.

[0125] 2,2-Bis(4-chlorophenyl)-2-hydroxyacetic acid (4m)

[0126] C 14 H9Cl2O3 - [MH] - :294.9934, found 294.9933.

[0127] 2-Hydroxy-2,2-di-p-toluic acid (4n)

[0128] 127.47, 80.38, 21.05. HRMS (ESI-) calculated as C 16 H 15 O3 - [MH] - :255.1027, found 255.1031.

[0129] 2-(4-Fluorophenyl)-2-hydroxy-2-(p-Tolyl)acetic acid (4o)

[0130] =243.4Hz), 141.14, 140.48 (d, J = 3.2Hz), 136.92, 129.60 (d, J = 8.3Hz), 128.75, 127.31, 114.72 (d, J = 21.3Hz), 80.10, 21.03. 19 F NMR (376MHz, DMSO-d6) δ-115.81.HRMS (ESI-) calculated as C 15 H 12 FO3 - [MH] - :259.0776, found 259.0774.

[0131] methyl 9-hydroxy-9H-xanthon-9-carboxylic acid (4p)

[0132] 174.89, 150.16, 129.91, 126.59, 123.41, 121.76, 116.78, 69.81, 53.95. HRMS (ESI+) calculated as C. 15 H 12 NaO4 + [M+Na] + :279.0628, found 279.0631.

[0133] 2-Hydroxy-2-phenyl-2-(thiophen-2-yl)methyl acetate (4q)

[0134] (m,1H),7.03–6.94(m,1H),4.47(s,1H),3.85(s,3H). 13 C NMR (101MHz, CDCl3) δ 173.83, 128.43, 128.22, 126.69, 126.56, 126.36, 125.92, 53.87. HRMS (ESI+) calculated as C 13 H 12 NaO3S + [M+Na] + :271.0399, found 271.0400.

[0135] 2-Hydroxy-2,2-bis(thiophen-2-yl)methyl acetate (4r)

[0136] 6.97(dd,J=5.1,3.6Hz,2H),4.71(s,1H),3.88(s,3H). 13 C NMR (101MHz, CDCl3) δ 172.81, 126.77, 126.01, 125.94, 76.52, 54.13. HRMS (ESI+) calculated as C 11 H 10 NaO3S2 + [M+Na] + :276.9964, found 276.9969.

[0137] 2-Hydroxy-3,3-dimethyl-2-((2-methyl-1-phenylprop-2-yl)oxy)carbonyl)butyric acid (6a)

[0138] Hz, 6H), 1.08 (s, 9H). 13 C NMR (101MHz, CDCl3) δ 169.96, 169.39, 135.96, 130.70, 128.10, 126.82, 87.81, 83.46, 47.04, 39.12, 25.55, 25.46, 25.30. HRMS (ESI-) calculated as C 17 H 23 O5 - [MH] - :307.1551, found 307.1552.

[0139] 2-(tert-Butoxycarbonyl)-2-hydroxy-3-methylhexanoic acid (6b)

[0140] 4H), 0.96–0.65(m,6H). 13 C NMR (101MHz, DMSO-d6) δ 172.32, 172.28, 170.16, 170.09, 82.96, 82.88, 81.68, 81.61, 37.56, 37.28, 33.57, 33.54, 27.91, 20.64, 20.59, 14.65, 14.50, 14.03. HRMS (ESI+) calculated as C 12 H 22 NaO5 + [M+Na] + :269.1359, found 269.1355.The drvalue was determined by 13 C NMR analysis of isolated product.

[0141] 2-(tert-Butoxycarbonyl)-2-hydroxyhexanoic acid (6c)

[0142] 4H), 0.81(t, J = 7.0 Hz, 3H). 13 C NMR (101MHz, DMSO-d6) δ 172.52, 170.27, 81.48, 79.12, 35.19, 27.93, 25.48, 22.75, 14.35. HRMS (ESI+) calculated as C 11 H 20 NaO5 + [M+Na] + :255.1203, found 255.1206.

[0143] 2-(tert-Butoxycarbonyl)-2-hydroxyhexyl-5-enoic acid (6d)

[0144] (m,2H),1.90–1.78(m,2H),1.40(s,9H). 13 C NMR (101MHz, DMSO-d6) δ 172.33, 170.13, 138.64, 115.26, 81.66, 78.80, 34.80, 27.93, 27.74. HRMS (ESI+) calculated as C 11 H 18 NaO5 + [M+Na] + :253.1046, found 253.1044.

[0145] 2-(tert-Butoxycarbonyl)-2-hydroxy-5-phenylpentanoic acid (6e)

[0146] 2.51(m,2H),1.84–1.70(m,2H),1.64–1.43(m,2H),1.36(s,9H). 13 C NMR (101MHz, DMSO-d6) δ 172.43, 170.21, 142.36, 128.72, 128.70, 126.15, 81.50, 79.06, 35.53, 34.97, 27.89, 25.30. HRMS (ESI-) calculated as C 16 H 21 O5 - [MH] - :293.1394, found 293.1390.

[0147] 3-((3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylhept-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecyl-1H-cyclopentane[a]phenanthrene-3-yl)oxy)-2-hydroxy-2-methyl-3-oxopropionic acid (6f)

[0148] 1.76(m,5H),1.63–0.93(m,21H),0.92–0.86(m,6H),0.71(s,3H). 13 C NMR (101MHz, DMSO-d6) δ 172.76, 170.90, 139.67, 122.71, 76.07, 74.63, 56.60, 56.13, 49.90, 42.32, 39.46, 37.78, 36.87, 36.53, 36.18, 35.75, 31.82, 28.28, 27.89, 27.45, 24.33, 23.80, 23.14, 23.12, 23.09, 22.84, 21.05, 19.40, 19.00, 12.10. HRMS (ESI+) calculated as C 31 H 50 NaO5 + [M+Na] + :525.3550, found 525.3553.

[0149] Methyl 2-hydroxy-2-methyl-3-(methyl(phenyl)amino)-3-oxopropionate (6g)

[0150] 141.53, 129.44, 128.85, 75.74, 52.82, 40.30, 24.01. HRMS (ESI+) calculated as C 12 H 15 NNaO4 + [M+Na] + :260.0893, found 260.0891.

[0151] Methyl 3-(ethyl(phenyl)amino)-2-hydroxy-2-methyl-3-oxopropionate (6h)

[0152] 1H),3.84(dt,J=14.2,7.0Hz,1H),3.72–3.54(m,4H),1.39(s,3H),1.15(t,J=7.2Hz,3H). 13C NMR (101MHz, CDCl3) δ 171.98, 169.48, 139.73, 129.85, 129.25, 128.98, 75.74, 52.70, 47.19, 23.93, 12.48. HRMS (ESI+) calculated as C 13 H 17 NNaO4 + [M+Na] + :274.1050, found 274.1045.

[0153] Methyl 3-(butyl(phenyl)amino)-2-hydroxy-2-methyl-3-oxopropionate (6i)

[0154] J = 7.3 Hz, 3H). 13 C NMR (101MHz, CDCl3) δ 172.04, 169.79, 140.08, 129.85, 129.26, 128.96, 75.83, 52.70, 52.13, 29.32, 23.98, 19.89, 13.82. HRMS (ESI+) calculated as C 15 H 21 NNaO4 + [M+Na] + :302.1363, found 302.1362.

[0155] Methyl 2-hydroxy-3-(isopropyl(phenyl)amino)-2-methyl-3-oxopropionate (6j)

[0156] NMR (101MHz, CDCl3) δ 171.84, 169.62, 135.40, 132.02, 131.73, 129.26, 128.61, 128.57, 75.91, 52.60, 48.97, 24.03, 20.62, 20.36. HRMS (ESI+) calculated as C 14 H 19 NNaO4 + [M+Na] + :288.1206, found 288.1203.

[0157] 2-(benzoyloxy)-2-methyl-3-oxo-3-(piperidin-1-yl)propionic acid (6k)

[0158] 169.92, 165.40, 164.09, 134.30, 129.80, 129.68, 129.44, 82.70, 66.52, 66.08, 46.58, 43.39, 21.51. HRMS(ESI+): Calculated as C 16 H 16 NaO3 + [M+Na] + :330.0948, found 330.0941.

[0159] 2-([1,1'-biphenyl]-4-yl)-2-hydroxyacetic acid methyl ester (8a)

[0160] 174.09, 141.46, 140.52, 137.13, 128.78, 127.46, 127.38, 127.10, 127.00, 72.62, 53.15. HRMS (ESI+) calculated as C 15 H 14 NaO3 + [M+Na] + :265.0835, found 265.0829.

[0161] 2-Hydroxy-2-(4'-methyl-[1,1'-biphenyl]-4-yl)methyl acetate (8b)

[0162] 137.63, 137.29, 136.83, 129.49, 127.17, 126.97, 126.92, 72.65, 53.12, 21.10. HRMS(ESI+) calculated as C 16 H 16 NaO3 + [M+Na] + :279.0992, found 279.0990.

[0163] 2-Hydroxy-2-(4′-(methylthio)-[1,1′-biphenyl]-4-yl)methyl acetate (8c)

[0164] 137.91, 137.24, 137.07, 127.41, 127.06, 127.03, 126.80, 72.60, 53.16, 15.78. HRMS (ESI+) calculated as C. 16 H 16 NaO3S + [M+Na] + :311.0712, found 311.0708.

[0165] 2-Hydroxy-2-(4-(thiophen-3-yl)phenyl)methyl acetate (8d)

[0166] NMR (101MHz, CDCl3) δ 174.11, 141.74, 137.00, 136.15, 127.10, 126.68, 126.36, 126.28, 120.64, 72.66, 53.14. HRMS (ESI+) calculated as C 13 H 12 NaO3S + [M+Na] + :271.0399, found 271.0395.

[0167] 2-Hydroxy-2-(naphth-2-yl)methyl acetate (8e)

[0168] (m,3H),5.33(d,J=5.4Hz,1H),3.75(s,3H),3.57(d,J=5.5Hz,1H). 13 C NMR (101MHz, CDCl3) δ 174.18, 135.59, 133.34, 133.19, 128.53, 128.14, 127.74, 126.40, 126.01, 124.13, 73.07, 53.13. HRMS (ESI+) calculated as C 13 H 12 NaO3 + [M+Na] + :239.0679, found 239.0679.

[0169] 2-Hydroxy-2-(phenanthrene-9-yl)methyl acetate (8f)

[0170] 7.52(m,4H),5.82(d,J=3.7Hz,1H),3.73(s,3H),3.55(d,J=4.4Hz,1H). 13 C NMR (101MHz, CDCl3) δ 174.72, 132.14, 130.96, 130.62, 129.61, 128.93, 127.69, 127.37, 126.96, 126.89, 126.65, 124.48, 123.26, 122.52, 72.15, 53.22. HRMS (ESI+) calculated as C 17 H 14 NaO3 + [M+Na] +:289.0835, found 289.0833.

[0171] Although specific embodiments of the present invention have been described in detail with reference to examples, they should not be construed as limiting the scope of protection of this patent. Various modifications and variations that can be made by those skilled in the art without inventive effort within the scope described in the claims are still within the scope of protection of this patent.

Claims

1. A kind A method for synthesizing -hydroxycarboxylic acid compounds, characterized in that, Includes the following steps: S1: Add the photosensitizer and base to the reaction substrate, then add the solvent and additive under a CO2 atmosphere, and mix well to obtain the reaction solution; the reaction substrate is a ketone compound, the additive is a mixture of N,N-diisopropylethylamine and chlorosilane; the photosensitizer is Ir(ppy)2(dtbbpy)PF6 or 3DPA2FBN; the base is potassium tert-butoxide or cesium carbonate; the chlorosilane is TESCl or TMSCl; the structural formula of the reaction substrate is shown in formula (I): Among them, R 1 It is aryl; R 2 It is an alkyl group; S2: Place the reaction solution obtained in S1 at a distance of 1-5 cm from a visible light source, stir the reaction at room temperature for 0.1 h to 48 h, quench the reaction with a quenching agent, and evaporate the solvent to obtain the crude product. S3: The crude product obtained from S2 is purified by rapid column chromatography to obtain... -Hydroxycarboxylic acid compounds; the The structural formula of -hydroxycarboxylic acid compounds is shown in formula (II): （Ⅱ）。 2. As described in claim 1 A method for synthesizing -hydroxycarboxylic acid compounds, characterized in that: The amount of photosensitizer is 0.1-5 mol% of the reaction substrate; the amount of base added is 1-3 times the equivalent of the reaction substrate; the amount of N,N-diisopropylethylamine added in the additive is 1-3 times the equivalent of the reaction substrate, and the amount of chlorosilane added is 1-3 times the equivalent of the reaction substrate.

3. As described in claim 1 or 2 A method for synthesizing -hydroxycarboxylic acid compounds, characterized in that: The solvent is DMF or DMA.

4. As described in claim 1 or 2 A method for synthesizing -hydroxycarboxylic acid compounds, characterized in that: The quenching agent is tetrabutylammonium fluoride or an aqueous solution of hydrochloric acid.

5. The method according to claim 1 A method for synthesizing -hydroxycarboxylic acid compounds, characterized in that: The visible light source is a 30W blue LED.

6. The method according to claim 1 A method for synthesizing -hydroxycarboxylic acid compounds, characterized in that: The eluent used for column chromatography purification in S3 is a mixture of petroleum ether, ethyl acetate and glacial acetic acid, with a volume ratio of petroleum ether to ethyl acetate of 10:1 and a mass fraction of glacial acetic acid of 0.1% to 1%.

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