A β-hydroxyketone compound and a synthesis method thereof

Abstract

The invention discloses a β-hydroxy ketone compound and a synthesis method thereof. The synthesis method uses enol ketone as a starting material, in an alkaline environment, through photocatalysis, water as an additive, under illumination and room temperature conditions, N-heterocyclic carbene borane as a hydrogen donor through a hydrogenation reaction to generate a β-hydroxy ketone compound. The reaction functional groups of the present invention are highly compatible, the yield is as high as 90%, and the product has functional group diversity. The β-hydroxy ketone compound of the present invention can be used as an organic synthesis precursor, and the 3-hydroxyl group in the skeleton structure of the β-hydroxy ketone compound can be further functionalized to obtain a drug molecule skeleton or a compound with potential biological activity.

Description

Technical Field

[0001] The invention relates to chemical medicine and a synthesis method, and in particular to a beta-hydroxyketone compound and a synthesis method thereof. Background Art

[0002] β-Hydroxyketone is a very important structural unit, widely present in natural products and bioactive molecules, and is also an important class of compounds in drug research. For example, compound A (J.Am.Chem.Soc.1981,103,3210.) is a secondary metabolite produced by Streptomyces erythromycin. In medicine, it has similar properties to penicillin and can be used as an antibiotic for some patients who are allergic to penicillin; compound B FK506 (J.Antibiot (Tokyo).1987,40,1249.), namely Tacrolimus, is a 23-ring-macrolide antibiotic extracted from soil fungi. It is an immunosuppressive drug that can effectively prevent rejection reactions in organ transplantation (structure as follows). In addition, β-hydroxyketone compounds are also widely used as organic synthesis intermediates.

[0003]

[0004] At present, the methods for synthesizing β-hydroxy ketone compounds include: (1) the hydroxyaldehyde reaction of connecting two aldehyde compounds under the catalysis of Bronsted acid or Bronsted base; (2) the Mukaiyama hydroxyaldehyde reaction of enol silyl ether compounds and aldehydes under the catalysis of Lewis acid; (3) the Reformatsky reaction of α-haloesters and aldehydes or ketones promoted by metals or metal salts. However, there are no reports on the synthesis of β-hydroxy ketone compounds using enol ketone as the starting material. Summary of the invention

[0005] Purpose of the invention: The purpose of the present invention is to provide β-hydroxyketone compounds and a photocatalytic synthesis method thereof, using enol ketones that are easy to prepare, have structural diversity and multiple reaction centers as starting materials, to synthesize β-hydroxyketone compounds with potential pharmaceutical activity under light conditions.

[0006] Technical solution: The present invention provides a β-hydroxyketone compound, the molecular structure of which is shown in general formula 1:

[0007]

[0008] R 1 is selected from the following groups: an aryl group, a furan ring, or a thiophene ring; R 2is an alkyl group; wherein the aryl group is a phenyl group or an aryl group with a substituent on the benzene ring, the substituent on the benzene ring is 1 to 5 of methyl, ethyl, methoxy, fluorine, chlorine, bromine, iodine, and trifluoromethyl, and the number of the substituents on the benzene ring is 1 to 5.

[0009] The present invention also provides a method for synthesizing the above-mentioned β-hydroxyketone compounds, specifically, using enol ketone 2 as a starting material, in an alkaline environment, catalyzed by a photocatalyst, water as an additive, under light and room temperature conditions, and using N-heterocyclic carbene borane 3a as a hydrogen donor to perform a hydrogenation reaction to generate a β-hydroxyketone compound of general formula 1 in one step.

[0010] The molecular structures of enol ketone 2 and N-heterocyclic carbene borane 3a are as follows:

[0011]

[0012] R 1 is selected from the following groups: aryl, furan ring or thiophene ring; R 2 It is an alkyl group such as methyl and ethyl.

[0013] The synthetic route is shown in the following reaction formula:

[0014]

[0015] in:

[0016] Furthermore, the light source of the illumination is white light, blue light or red light, preferably one of white light or blue light.

[0017] Furthermore, the photocatalyst is one of [Ir(ppy)2(dtbbpy)][PF6], Ru(bpy)3(PF)6, Eosin Y or 4-CzIPN, preferably one of Ru(bpy)3(PF)6 or 4-CzIPN.

[0018] Furthermore, the molar ratio of enol ketone 2 to the photocatalyst is 1:0.01-1:0.1, preferably 1:0.01-1:0.05.

[0019] Furthermore, the base in the alkaline environment is one or more of NaH, DBU, Cs2CO3, K2CO3, or NaOH, preferably one or two of NaH or K2CO3.

[0020] Further, the molar ratio of enol ketone 2 to the base is 1:0.1-1:2, preferably the molar ratio is 1:0.2-1:1.

[0021] Furthermore, the additive is H2O, and the molar ratio of enol ketone 2 to the additive is 1:0.1-1:5, preferably the molar ratio is 1:1-1:3.

[0022] Furthermore, the molar ratio of enol ketone 2 to N-heterocyclic carbene borane 3a is 1:0.5-1:4, preferably 1:1-1:3.

[0023] Further, the reaction solvent is a mixture of one or two of N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), acetonitrile (MeCN), toluene, dichloromethane (DCM), 1,4-dioxane, 1,2-dichloroethane (DCE) and ethanol, preferably the aprotic polar solvent acetonitrile (MeCN); the molar concentration of enol ketone 2 in the reaction solvent is 0.05-1.0M.

[0024] Furthermore, the reaction atmosphere is air, oxygen, nitrogen or argon; the reaction time is 0.5-48 hours, preferably 2-24 hours; and the reaction temperature is 10-120°C.

[0025] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0026] 1) Synthetic enol ketone 2 has structural diversity and good functional group tolerance, and can be used to synthesize β-hydroxy ketone compounds 1 of different types and structures, so it has a wide range of applications.

[0027] 2) Synthesis of enol ketone 2 and N-heterocyclic carbene borane 3 are both easy to prepare, the raw materials are cheap and readily available, the cost is low, and they are easy to industrialize.

[0028] 3) The synthesis of β-hydroxyketone compounds has good functional group tolerance and diversity, and therefore has a wide range of applications.

[0029] 4) The hydroxyl group at position 3 in the skeleton structure of β-hydroxyketone compound 1 is a group that can be further functionalized, and this structure can be used as an intermediate in the structure of drugs and chemical products.

[0030] 5) This synthesis method can be achieved on a gram scale and has great implementation value and social and economic benefits.

[0031] 6) A β-hydroxyketone mother ring structure with potential drug activity is obtained, the operation is simple, and the yield of the target product is good. DETAILED DESCRIPTION

[0032] The present application is described in detail below in conjunction with specific embodiments.

[0033] The synthesis of the starting materials enol ketone 2 and N-heterocyclic carbene borane 3a in the following examples can be prepared according to the prior art, for example:

[0034] Synthesis of Enol Ketone 2:

[0035] At 120°C, phenylacetone derivative A reacts with 1,1-dimethoxy-N,N-dimethylmethylamine B in a small amount of water to generate enol ketone 2 (reaction formula 1).

[0036]

[0037] The specific process is: add 1,1-dimethoxy-N,N-dimethylmethylamine B (10mmol) and H2O (5mmol) to the phenylpropiophenone derivative A (5mmol), stir and react in an oil bath at 120°C, and detect by TLC. When the raw material phenylpropiophenone derivative reacts completely, the reaction is stopped, and after cooling to room temperature, the volatile components are removed under reduced pressure, and then separated by silica gel column chromatography (eluent is petroleum ether (60-90°C) / ethyl acetate, v / v=10:1), to obtain the target product 2. The target product is confirmed by nuclear magnetic resonance spectroscopy.

[0038] Synthesis of N-heterocyclic carbene borane 3a:

[0039] After methyl iodide is added to a dichloromethane solution of N-methylimidazole C and reacted for a period of time, the reaction solution is concentrated and dried in vacuo to obtain a salt-like product D, and then the product D is reacted with sodium borohydride in toluene to generate N-heterocyclic carbene borane 3a (reaction formula 2).

[0040]

[0041] The specific process is as follows: iodomethane (12 mmol) is slowly added dropwise to a DCM (10 mL) solution of N-methylimidazole C (10 mmol), and after stirring for 1 hour, the reaction mixture is placed under reduced pressure to remove volatile components to prepare a salt sample D; a 100 mL flask is taken, the salt sample D is dissolved in toluene (10 mL), and then sodium borohydride (12 mmol) is added, and the flask is placed in a 125°C oil bath for reaction for 24 hours, the hot reaction solvent is carefully poured out from the insoluble mixture, and the remaining residue is extracted with hot toluene. The organic extract is cooled to room temperature, the volatile components are removed under reduced pressure, and then recrystallized to obtain the target product 3a. The target product is confirmed by nuclear magnetic resonance spectroscopy.

[0042] R 1 Selected from the following groups: aryl, furan ring or thiophene ring;

[0043] R 2 is an alkyl group;

[0044] The aryl group is phenyl or an aryl group with a substituent on the benzene ring, the substituent on the benzene ring is 1-5 of methyl, ethyl, methoxy, fluorine, chlorine, bromine, iodine, and trifluoromethyl, and the number of the substituents on the benzene ring is 1-5.

[0045] The alkyl group is a C1-C6 alkyl group.

[0046] The following examples are helpful to further understand the present invention, but the contents of the present invention are not limited thereto.

[0047] Example 1

[0048]

[0049] Weigh enol ketone 2a (0.5mmol), N-heterocyclic carbene borane 3a (2.0mmol), [Ir(ppy)2(dtbbpy)][PF6] (3mol%), and NaH (0.1mmol) in turn and add them to a photoreaction tube, add H2O (0.5mmol) and DCM 5mL under oxygen atmosphere, and place under blue LEDs (30W) for 10 hours at 40°C. After the reaction, extract with dichloromethane and saturated brine, collect the organic phase, dry with anhydrous sodium sulfate, filter, remove volatile components under reduced pressure, and then separate by silica gel column chromatography (eluent is petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and obtain colorless oily target product 1a (76mg, yield 85%). The target product is confirmed by nuclear magnetic resonance spectroscopy.

[0050] Example 2

[0051]

[0052] Enol ketone 2b (0.5mmol), N-heterocyclic carbene borane 3a (0.25mmol), Ru(bpy)3(PF)6 (1mol%), DBU (0.25mmol) were weighed in turn and added to a photoreaction tube, H2O (1.0mmol) and DMSO 5mL were added under air atmosphere, and the mixture was placed under white LEDs (30W) for 12 hours at 25°C. After the reaction, dichloromethane and saturated brine were extracted, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the volatile components were removed under reduced pressure, and then separated by silica gel column chromatography (eluent was petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), to obtain the colorless oily target product 1b (86mg, yield 90%). The target product was confirmed by nuclear magnetic resonance spectroscopy.

[0053] Example 3

[0054]

[0055] Weigh enol ketone 2c (0.5mmol), N-heterocyclic carbene borane 3a (1.5mmol), Eosin Y (10mol%), Cs2CO3 (0.4mmol) in turn and add them to a photoreaction tube, add H2O (1.5mmol) and DMF 5mL under nitrogen atmosphere, and place under red LEDs (30W) for 10°C for reaction for 24 hours. After the reaction is completed, extract with dichloromethane and saturated brine, collect the organic phase, dry with anhydrous sodium sulfate, filter, remove volatile components under reduced pressure, and then separate by silica gel column chromatography (eluent is petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and obtain colorless oily target product 1c (84mg, yield 87%). The target product is confirmed by nuclear magnetic resonance spectroscopy.

[0056] Example 4

[0057]

[0058] Enol ketone 2d (0.5mmol), N-heterocyclic carbene borane 3a (1.5mmol), 4-CzIPN (1mol%), K2CO3 (0.15mmol) were weighed in sequence and added to a photoreaction tube. H2O (1.0mmol) and acetonitrile 5mL were added under nitrogen atmosphere, and the mixture was placed under blue LEDs (30W) for 8 hours at 25°C. After the reaction, dichloromethane and saturated brine were extracted, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the volatile components were removed under reduced pressure. Then, silica gel column chromatography was used for separation (eluent was petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and the target product 1d (57mg, yield 59%) was obtained as a colorless oil. The target product was confirmed by nuclear magnetic resonance spectroscopy.

[0059] Example 5

[0060]

[0061] Weigh enol ketone 2e (0.5mmol), N-heterocyclic carbene borane 3a (1.0mmol), 4-CzIPN (1mol%), K2CO3 (0.5mmol) in turn and add them to a photoreaction tube, add H2O (2.0mmol) and acetonitrile 5mL under argon atmosphere, and place under blue LEDs (30W) for 25°C for 48 hours. After the reaction is completed, extract with dichloromethane and saturated brine, collect the organic phase, dry it with anhydrous sodium sulfate, filter it, remove the volatile components under reduced pressure, and then separate it with silica gel column chromatography (eluent is petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and obtain the colorless oily target product 1e (73mg, yield 80%). The target product is confirmed by nuclear magnetic resonance spectroscopy.

[0062] Example 6

[0063]

[0064] Enol ketone 2f (0.5mmol), N-heterocyclic carbene borane 3a (0.75mmol), [Ir(ppy)2(dtbbpy)][PF6] (2mol%), Cs2CO3 (0.15mmol) were weighed and added to a photoreaction tube, H2O (0.25mmol) and 1,4-dioxane 5mL were added under oxygen atmosphere, and the mixture was placed under white LEDs (30W) for 1 hour at 100℃. After the reaction, the mixture was extracted with dichloromethane and saturated brine, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the volatile components were removed under reduced pressure, and then separated by silica gel column chromatography (eluent was petroleum ether (60-90℃) / ethyl acetate, v / v=5:1), to obtain the target product 1f (74mg, yield 75%) as a colorless oil. The target product was confirmed by nuclear magnetic resonance spectroscopy.

[0065] Example 7

[0066]

[0067] 2g (0.5mmol) of enol ketone, N-heterocyclic carbene borane 3a (0.65mmol), 4-CzIPN (5mol%), and DBU (0.3mmol) were weighed in sequence and added to a photoreaction tube. H2O (0.5mmol) and DCE 5mL were added under nitrogen atmosphere, and the mixture was placed under red LEDs (30W) for 0.5 hours at 80°C. After the reaction, the mixture was extracted with dichloromethane and saturated brine, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the volatile components were removed under reduced pressure. Then, the mixture was separated by silica gel column chromatography (eluent was petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and 1g (69mg, yield 70%) of the target product was obtained as a colorless oil. The target product was confirmed by nuclear magnetic resonance spectroscopy.

[0068] Example 8

[0069]

[0070] Weigh enol ketone 2h (0.5mmol), N-heterocyclic carbene borane 3a (0.6mmol), Eosin Y (3mol%), and NaH (0.05mmol) in turn and add them into a photoreaction tube. Add H2O (1.0mmol) and 5mL of ethanol under argon atmosphere, and place under blue LEDs (30W) for 24 hours at 25°C. After the reaction, extract with dichloromethane and saturated brine, collect the organic phase, dry with anhydrous sodium sulfate, filter, remove volatile components under reduced pressure, and then separate by silica gel column chromatography (eluent is petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and obtain the target product 1h (98mg, yield 81%) as a colorless oil. The target product is confirmed by nuclear magnetic resonance spectroscopy.

[0071] Example 9

[0072]

[0073] Enol ketone 2i (0.5 mmol), N-heterocyclic carbene borane 3a (0.75 mmol), [Ir(ppy)2(dtbbpy)][PF6] (10 mol%), and NaOH (0.25 mmol) were weighed in sequence and added to a photoreaction tube. H2O (0.05 mmol) and DCM 5 mL were added under an oxygen atmosphere, and the mixture was placed under blue LEDs (30 W) for 8 hours at 25°C. After the reaction, the mixture was extracted with dichloromethane and saturated brine, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the volatile components were removed under reduced pressure. Then, the mixture was separated by silica gel column chromatography (eluent was petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and the target product 1i (73 mg, yield 60%) was obtained as a colorless oil. The target product was confirmed by nuclear magnetic resonance spectroscopy.

[0074] Example 10

[0075]

[0076] Weigh enol ketone 2j (0.5mmol), N-heterocyclic carbene borane 3a (1.5mmol), Eosin Y (5mol%), K2CO3 (0.15mmol) in turn and add them to a photoreaction tube, add H2O (1.5mmol) and DCE 5mL under nitrogen atmosphere, and place under red LEDs (30W) for 10 hours at 50°C. After the reaction, extract with dichloromethane and saturated brine, collect the organic phase, dry with anhydrous sodium sulfate, filter, remove volatile components under reduced pressure, and then separate by silica gel column chromatography (eluent is petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and obtain colorless oily target product 1j (72mg, yield 62%). The target product is confirmed by nuclear magnetic resonance spectroscopy.

[0077] Embodiment 11

[0078]

[0079] Enol ketone 2k (0.5 mmol), N-heterocyclic carbene borane 3a (0.5 mmol), Ru(bpy)3(PF)6 (3 mol%), and NaH (0.2 mmol) were weighed in sequence and added to a photoreaction tube. H2O (2.0 mmol) and acetonitrile 5 mL were added under air atmosphere, and the mixture was placed under blue LEDs (30 W) at 45°C for 6 hours. After the reaction, the mixture was extracted with dichloromethane and saturated brine, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the volatile components were removed under reduced pressure. Then, the mixture was separated by silica gel column chromatography (eluent was petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and the target product 1k (57 mg, yield 55%) was obtained as a colorless oil. The target product was confirmed by nuclear magnetic resonance spectroscopy.

[0080] Example 12

[0081]

[0082] Enol ketone 2l (0.5mmol), N-heterocyclic carbene borane 3a (1.25mmol), Eosin Y (7mol%), DBU (0.35mmol) were weighed in sequence and added to a photoreaction tube, H2O (1.0mmol) and toluene 5mL were added under oxygen atmosphere, and the mixture was placed under blue LEDs (30W) for 12 hours at 25°C. After the reaction, dichloromethane and saturated brine were extracted, the organic phase was collected, dried over anhydrous sodium sulfate, filtered, and the volatile components were removed under reduced pressure, and then separated by silica gel column chromatography (eluent was petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), to obtain the target product 1l (64mg, yield 75%) as a colorless oil. The target product was confirmed by nuclear magnetic resonance spectroscopy.

[0083] Example 13

[0084]

[0085] Weigh enol ketone 2m (0.5mmol), N-heterocyclic carbene borane 3a (1.0mmol), [Ir(ppy)2(dtbbpy)][PF6] (1mol%), K2CO3 (0.75mmol) in turn and add them to a photoreaction tube, add H2O (1.5mmol) and DMSO 5mL under nitrogen atmosphere, and place under blue LEDs (30W) for 20℃ for 8 hours. After the reaction, extract with dichloromethane and saturated brine, collect the organic phase, dry with anhydrous sodium sulfate, filter, remove volatile components under reduced pressure, and then separate by silica gel column chromatography (eluent is petroleum ether (60-90℃) / ethyl acetate, v / v=5:1), and obtain colorless oily target product 1m (59mg, yield 77%). The target product is confirmed by nuclear magnetic resonance spectroscopy.

[0086] Embodiment 14

[0087]

[0088] Weigh enol ketone 2n (0.5mmol), N-heterocyclic carbene borane 3a (0.5mmol), 4-CzIPN (2mol%), and NaOH (0.15mmol) in turn and add them to a photoreaction tube. Add H2O (0.5mmol) and acetonitrile 5mL under nitrogen atmosphere, and place under white LEDs (30W) for 25°C for 15 hours. After the reaction is completed, extract with dichloromethane and saturated brine, collect the organic phase, dry it with anhydrous sodium sulfate, filter it, remove the volatile components under reduced pressure, and then separate it with silica gel column chromatography (eluent is petroleum ether (60-90°C) / ethyl acetate, v / v=5:1), and obtain the colorless oily target product 1n (78mg, yield 88%). The target product is confirmed by nuclear magnetic resonance spectroscopy.

[0089] Characterization data of typical compounds

[0090] 3-Hydroxy-2-methyl-1-(p-tolyl)propan-1-one (1a), colorless, transparent, oily liquid. 1 H NMR (400MHz, CDCl3) δ7.86(d,J=8.1Hz,2H),7.27(d,J=8.2Hz,2H),3.90(d,J=6.3Hz,1H),3 .79(d,J=10.9Hz,1H),3.71–3.56(m,1H),2.47(s,1H),2.41(s,3H),1.22(d,J=7.2Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ204.3,144.4,133.7,129.5,128.7,64.7,42.8,21.8,14.8.

[0091] 1-(4-Ethylphenyl)-3-hydroxy-2-methylpropane-1-one (1b), colorless, transparent, oily liquid. 1 H NMR (400MHz, CDCl3) δ7.88(d,J=8.1Hz,2H),7.28(d,J=8.1Hz,2H),3.91(dd,J=11.0,7.0Hz,1H),3.77(dd,J=11.1 ,4.2Hz,1H),3.71–3.57(m,1H),2.70(q,J=7.6Hz,2H),2.58(s,1H),1.25(t,J=7.7Hz,3H),1.21(d,J=7.3Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ204.2,150.5,133.9,128.8,128.3,64.7,42.8,29.0,15.3,14.8.

[0092] 3-Hydroxy-1-(4-methoxyphenyl)-2-methylpropane-1-one (1c), colorless, transparent, oily liquid. 1 H NMR(400MHz, CDCl3)δ7.91(d,J=8.7Hz,2H),6.90(d,J=8.7Hz,2H),3.87(dd,J=10.9,7.1Hz,1H), 3.82(s,3H),3.72(dd,J=11.0,4.3Hz,1H),3.64–3.53(m,1H),2.84(s,1H),1.17(d,J=7.2Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ203.0,163.7,130.8,129.1,113.9,64.7,55.5,42.5,14.8.

[0093] 3-Hydroxy-1-(2-methoxyphenyl)-2-methylpropan-1-one (1d), colorless, transparent oily liquid. 1H NMR (400MHz, CDCl3) δ7.58 (dd, J=7.7, 1.8Hz, 1H), 7.45 (ddd, J=8.4, 7.4, 1.8Hz, 1H), 6.99 (td, J=7.5, 1.0Hz, 1H), 6.95 (d, J=8.4Hz, 1H),3.88(s,3H),3.83(dd,J=11.8,5.6Hz,1H),3.79–3.72(m,1H),3.70–3.61(m,1H),2.55(t,J=6.2Hz,1H),1.14(d,J=7.2Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ207.4,158.1,133.5,130.4,128.1,120.9,111.5,64.7,55.6,47.6,13.7.

[0094] 1-(4-Fluorophenyl)-3-hydroxy-2-methylpropan-1-one (1e), colorless, transparent, oily liquid. 1 H NMR (400MHz, CDCl3) δ8.08–7.92(m,2H),7.13(t,J=8.5Hz,2H),3.97–3.88(m,1H),3 .77(dd,J=11.0,4.2Hz,1H),3.70–3.55(m,1H),2.44(s,1H),1.21(d,J=7.2Hz,3H). 13 C{ 1 H} NMR (100MHz, CDCl3) δ202.9, 166.0 (d, J = 255.2Hz), 132.7 (d, J = 3.1Hz), 131.2 (d, J = 9.3Hz), 116.0 (d, J = 21.9Hz), 64.7, 43.0, 14.7. 19 F NMR (376MHz, CDCl3) δ-104.74 (s, 1F).

[0095] 1-(4-Chlorophenyl)-3-hydroxy-2-methylpropane-1-one (1f), colorless, transparent, oily liquid. 1 H NMR (400MHz, CDCl3) δ7.86(d,J=8.4Hz,2H),7.40(d,J=8.4Hz,2H),3.89(dd,J=10.9,7.4Hz ,1H),3.72(dd,J=11.0,4.2Hz,1H),3.67–3.53(m,1H),2.73(s,1H),1.17(d,J=7.2Hz,3H). 13 C{ 1H}NMR (100MHz, CDCl3) δ203.1,139.8,134.5,129.9,129.1,64.5,43.1,14.5.

[0096] 1-(3-Chlorophenyl)-3-hydroxy-2-methylpropan-1-one (1g), colorless transparent oily liquid. 1 H NMR (400MHz, CDCl3) δ7.89(s,1H),7.79(d,J=7.7Hz,1H),7.50(d,J=8.0Hz,1H),7.38(t,J=7.9Hz,1H),3.90( dd,J=11.0,7.3Hz,1H),3.72(dd,J=11.0,4.4Hz,1H),3.66–3.53(m,1H),2.75(s,1H),1.16(d,J=7.2Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ203.1,137.8,135.1,133.2,130.1,128.5,126.6,64.5,43.3,14.5.

[0097] 1-(4-Bromophenyl)-3-hydroxy-2-methylpropan-1-one (1h), colorless, transparent oily liquid. 1 H NMR (400MHz, CDCl3) δ7.81(d,J=8.4Hz,2H),7.60(d,J=8.4Hz,2H),3.91(dd,J=10.8,7.3Hz ,1H),3.76(dd,J=10.9,3.9Hz,1H),3.66–3.53(m,1H),2.51(s,1H),1.19(d,J=7.2Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ203.4,135.0,132.1,130.1,128.6,64.6,43.1,14.6.

[0098] 1-(3-Bromophenyl)-3-hydroxy-2-methylpropane-1-one (1i), colorless, transparent, oily liquid. 1H NMR (400MHz, CDCl3) δ8.05(s,1H),7.84(d,J=7.8Hz,1H),7.66(d,J=7.9Hz,1H),7.32(t,J=7.9Hz,1H),3.90( dd,J=10.9,7.3Hz,1H),3.73(dd,J=11.0,4.3Hz,1H),3.65–3.53(m,1H),2.65(s,1H),1.17(d,J=7.2Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ203.0,138.0,136.2,131.5,130.4,127.0,123.1,64.5,43.3,14.5.

[0099] 1-(3,4-Dichlorophenyl)-3-hydroxy-2-methylpropane-1-one (1j), colorless, transparent, oily liquid. 1 H NMR (400MHz, CDCl3) δ8.00(s,1H),7.75(dd,J=8.3,1.5Hz,1H),7.52(d,J=8.3Hz,1H),3.90(dd,J=10 .8,7.5Hz,1H),3.73(dd,J=11.0,4.2Hz,1H),3.63–3.51(m,1H),2.62(s,1H),1.17(d,J=7.2Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ202.1,137.9,135.9,133.5,130.9,130.5,127.5,64.5,43.3,14.4.

[0100] 1-(Benzo[d][1,3]dioxol-5-yl)-3-hydroxy-2-methylpropane-1-one (1k), colorless, transparent, oily liquid. 1 HNMR (400MHz, CDCl3) δ7.55(dd,J=8.2,1.2Hz,1H),7.41(s,1H),6.84(d,J=8.2Hz,1H),6.03(s,2H),3.88(d d,J=11.0,7.1Hz,1H),3.74(dd,J=11.0,4.2Hz,1H),3.61–3.50(m,1H),2.60(s,1H),1.19(d,J=7.2Hz,3H). 13 C{ 1H}NMR (100MHz, CDCl3) δ202.5,152.1,148.4,131.0,124.9,108.2,108.1,102.0,64.8,42.7,14.9.

[0101] 3-Hydroxy-2-methyl-1-(thiophen-2-yl)propan-1-one (1l), colorless, transparent, oily liquid. 1 H NMR (400MHz, CDCl3) δ7.81–7.70(m,1H),7.64(dd,J=4.8,0.7Hz,1H),7.12(dd,J=4.7,4.0Hz,1H),3.89(dd ,J=10.9,7.3Hz,1H),3.74(dd,J=11.0,4.4Hz,1H),3.57–3.42(m,1H),2.61(s,1H),1.24(d,J=7.2Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ197.1,143.7,134.4,132.6,128.4,64.7,44.8,15.0.

[0102] 1-(Furan-2-yl)-3-hydroxy-2-methylpropan-1-one (1m), colorless, transparent, oily liquid. 1 H NMR (400MHz, CDCl3) δ7.58–7.55(m,1H),7.21(d,J=3.6Hz,1H),6.50(dd,J=3.5,1.6Hz,1H),3.85 (t,J=7.6Hz,1H),3.69(d,J=10.8Hz,1H),3.49–3.35(m,1H),2.81(s,1H),1.17(d,J=7.2Hz,3H). 13 C{ 1 H}NMR (100MHz, CDCl3) δ192.8,152.2,146.9,118.3,112.4,64.3,43.9,14.1.

[0103] 2-(Hydroxymethyl)-1-phenylbutan-1-one (1n), colorless, transparent, oily liquid. 1H NMR(400MHz,CDCl3)δ7.95(d,J=7.4Hz,2H),7.57(t,J=7.3Hz,1H),7.47(t,J=7.6Hz,2H),4.03–3.91(m,1H),3.84(d,J=10.9Hz,1H),3.59–3.49(m,1H),2.45(s,1H),1.82–1.73(m,1H),1.72–1.60(m,1H),0.95(t,J=7.5Hz,3H). 13 C{ 1 H}NMR(100MHz,CDCl3)δ204.8,137.0,133.4,128.8,128.5,62.7,49.7,22.5,11.9。

Claims

1. A method for preparing a β-hydroxyketone compound, characterized in that: Using enol ketone 2 as the starting material, in an alkaline environment, under the catalysis of a photocatalyst, with water as an additive, under light and room temperature conditions, N-heterocyclic carbene borane 3a as a hydrogen donor, a β-hydroxy ketone compound shown in general formula 1 is generated through a hydrogenation reaction; The synthetic route is shown in the following reaction formula: Among them, R 1 is selected from the following groups: aryl, furan ring or thiophene ring; R 2 is an alkyl group; wherein the aryl group is a phenyl group or an aryl group with a substituent on the benzene ring, the substituent on the benzene ring is 1 to 5 of methyl, ethyl, methoxy, fluorine, chlorine, bromine, iodine, and trifluoromethyl, and the number of the substituents on the benzene ring is 1 to 5; The photocatalyst is one of [Ir(ppy)2(dtbbpy)][PF6], Ru(bpy)3(PF)6, Eosin Y or 4-CzIPN; the base in the alkaline environment is one or more of NaH, DBU, Cs2CO3, K2CO3 or NaOH; the reaction solvent is one or a mixture of two of N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, toluene, dichloromethane, 1,4-dioxane, 1,2-dichloroethane and ethanol.

2. The method for preparing β-hydroxyketone compounds according to claim 1, characterized in that: The molar ratio of enol ketone 2 to the photocatalyst is 1:0.01-1:0.

1.

3. The method for preparing β-hydroxyketone compounds according to claim 1, characterized in that: The molar ratio of enol ketone 2 to base is 1:0.1-1:

2.

4. The method for preparing β-hydroxyketone compounds according to claim 1, characterized in that: The additive is H2O, and the molar ratio of enol ketone 2 to the additive is 1:0.1-1:

5.

5. The method for preparing β-hydroxyketone compounds according to claim 1, characterized in that: The molar ratio of enol ketone 2 to N-heterocyclic carbene borane 3a is 1:0.5-1:

4.

6. The method for preparing β-hydroxyketone compounds according to claim 1, characterized in that: The molar concentration of enol ketone 2 in the reaction solvent is 0.05-1.0 M.

7. The method for preparing β-hydroxyketone compounds according to claim 1, characterized in that: The reaction atmosphere is air, oxygen, nitrogen or argon; the reaction time is 0.5-48 hours.

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