Alpha-boryl ketone compound and synthesis method thereof

Abstract

The synthesis method specifically comprises the following steps: S1, sequentially adding phenylethynyl boric acid methyl iminodiacetate, trifluoroacetic acid and water into a pressure-resistant sealed reaction tube, carrying out a stirring reaction at 40-60 DEG C for 12-24 h, and monitoring the reaction by adopting TLC in the reaction process; s2, after the reaction is completed, adding ethyl acetate for quenching reaction, extracting with a saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporating to remove the organic solvent; and S3, carrying out silica gel purification and eluent leaching to obtain a product. According to the invention, phenylacetylene boric acid methyl imino diacetate is used as a raw material, and the alpha-boryl ketone compound is directly prepared through a one-step hydration reaction in an acidic mixed solvent system. The reaction conditions are mild, and beta-oxo reaction can be efficiently and selectively carried out to synthesize the alpha-boryl ketone compound only at 40-60 DEG C without harsh conditions such as high temperature and high pressure.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically an α-boronyl ketone compound and its synthesis method. Background Technology

[0002] α-Boronyl ketones are important intermediates in organic synthesis and have wide applications in medicinal chemistry, functional materials, and asymmetric catalysis. Due to the special physical properties of boron atoms, boron-containing compounds are often used as enzyme inhibitors, such as bortezomib (trade name Velcade), which was approved for marketing by the U.S. Food and Drug Administration in 2013.

[0003] In previous studies of α-boronyl ketones, traditional synthetic methods mainly relied on metal catalysts, such as palladium catalysts. In 2018, Yudin et al. (Corless VB, Holownia A, Foy H, et al. Org Lett. 2018; 20(17): 5300-5303.) selectively oxidized MIDA-protected alkenylboronic esters to α-boronyl ketones via a palladium-catalyzed TBHP-mediated Wacker oxidation reaction. However, this reaction requires a high catalyst loading and an excess of TBHP, posing certain safety and economic challenges. In recent years, although metal-free catalytic systems have been reported, they still have significant drawbacks. For example, Wang H et al. (Chen ZH, Su XX, Li Q, Wu JQ, Ou TM, Wang H. Org Lett. 2023; 25(7): 1099-1103.) used AcCl and H2O in HFIP to hydrate arylethynyl B (MIDA) at room temperature to generate α-boronyl aryl ketones. However, for aliphatic ethynyl B (MIDA), strong oxidants (such as m-CPBA) are required, which may pose safety hazards and greatly limit its application in industrial production. Therefore, developing an efficient, mild, metal-catalyzed one-step synthesis method has become a key technical challenge that urgently needs to be overcome in this field.

[0004] This application is submitted in response to the above-mentioned issues. Summary of the Invention

[0005] This invention proposes a simple method for constructing boron-based ketones using phenylethynylboronic acid methyliminodiacetic acid ester as a direct raw material via acid-catalyzed hydration reaction. This method aims to overcome the shortcomings of existing processes and improve synthesis efficiency and practicality.

[0006] The primary objective of this invention is to provide an α-boronyl ketone compound with the following structural formula:

[0007]

[0008] Wherein, R is a phenyl or a substituted phenyl;

[0009] The substituent of the substituted phenyl group is C. 1-4 Alkyl, halogen, C 1-2 One or more of the alkoxy groups.

[0010] Preferably, the substituent of the substituted phenyl group is one or more selected from methyl, ethyl, isopropyl, butyl, halogen, methoxy, and ethoxy.

[0011] The second objective of this invention is to provide a method for synthesizing the above-mentioned α-boronyl ketone compounds, the synthetic route of which is as follows:

[0012]

[0013] Includes the following steps:

[0014] S1: Add methyliminodiacetic acid ester of phenylethynylboronic acid, trifluoroacetic acid and water sequentially into a pressure-resistant and sealed reaction tube, and stir the reaction at 40-60℃ for 12-24h. The reaction is monitored by TLC during the process.

[0015] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent.

[0016] S3: The product was then purified by silica gel and eluted with an eluent (n-hexane:ethyl acetate = 1:1-1:3) to obtain the product.

[0017] Using the above-described technical solution, α-boronyl ketone compounds are directly prepared from phenylethynylboronic acid methyliminodiacetic acid ester via a one-step hydration reaction in an acidic mixed solvent system. In this invention, the carbon-carbon triple bond in phenylethynylboronic acid methyliminodiacetic acid ester is bonded to a proton to form an alkenyl cationic intermediate. At this point, the trifluoroacetate ion acts as a nucleophile, attacking the alkenyl cationic intermediate to generate a trifluoroacetate intermediate. Subsequently, the trifluoroacetate intermediate undergoes hydrolysis, and the carbonyl carbon atom undergoes a nucleophilic addition reaction with water molecules to generate an intermediate with a hydroxyl group attached to the carbonyl carbon atom. Finally, this intermediate undergoes keto-enol tautomerism to generate an α-boronyl ketone.

[0018] Preferably, the molar ratio of phenylethynylboronic acid methyliminodiacetic acid ester and water in step S1 is 1:1-3.

[0019] Preferably, step S1 further includes acetone.

[0020] Using the above technical solution, this invention employs trifluoroacetic acid (TFA) as a catalyst to promote the hydration reaction of alkynes through protonic acid activation, achieving highly selective conversion. Compared with traditional processes, this invention has advantages such as simple operation, mild conditions, environmental friendliness, and low cost, and solves problems such as multi-step synthesis, metal residues, and poor functional group compatibility, providing a new approach for the large-scale preparation of boron-containing functional molecules.

[0021] Preferably, the eluent in step S3 is prepared by mixing n-hexane and ethyl acetate in a volume ratio of 1:1-3.

[0022] The beneficial effects of this invention are:

[0023] This invention utilizes methyliminodiacetic acid phenylethynylboronic acid as a raw material to directly prepare α-boronyl ketone compounds via a one-step hydration reaction in an acidic mixed solvent system. The reaction is conducted under mild conditions, requiring only 40-60°C, without the need for harsh conditions such as high temperature and high pressure. This allows for the efficient and selective synthesis of α-boronyl ketone compounds through β-oxochemical reactions. The reaction has a wide range of applicable substrates and strong functional group compatibility, with reaction conditions compatible with alkyl, alkoxy, and halogen functional groups. Furthermore, the carbon-boron bond is well preserved during the reaction, and the boron groups in the product can be further used for functionalization reactions. Moreover, the reaction conditions are environmentally friendly and economical; the solvent TFA can be recovered and reused through distillation, reducing costs and waste emissions. This invention provides a new, efficient, economical, and environmentally friendly route for the synthesis of α-boronyl ketone compounds, possessing significant application value. Detailed Implementation

[0024] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below in conjunction with specific embodiments.

[0025] Example 1

[0026] Synthetic route of compound R1:

[0027]

[0028] Specific synthesis steps:

[0029] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S1), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0030] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction three times with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent.

[0031] S3: After purification with silica gel and elution with eluent (hexane and ethyl acetate in a volume ratio of 1:1), product R1 was obtained with a yield of 65%.

[0032] The NMR data are as follows:

[0033] 1 H NMR (400MHz, DMSO) δ8.02–7.93(m,2H),7.66–7.57(m,1H),7.51(t,J=7.7Hz,2 H), 4.26 (d, J = 17.0Hz, 2H), 4.06 (d, J = 17.0Hz, 2H), 3.01 (s, 3H), 2.69 (s, 2H).

[0034] 13 C NMR (101MHz, DMSO) δ201.84,169.12,138.28,133.23,128.91,128.89,62.47,46.76.

[0035] 11 B NMR (128MHz, DMSO) δ 14.28.

[0036] Example 2

[0037] Synthetic route of compound R2:

[0038]

[0039] Specific synthesis steps:

[0040] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S2), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0041] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction three times with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent.

[0042] S3: After purification with silica gel and elution with eluent (hexane to ethyl acetate in a volume ratio of 1:3), product R2 was obtained with a yield of 60%.

[0043] The NMR data are as follows:

[0044] 1H NMR (400MHz, DMSO) δ7.86 (d, J=8.2Hz, 2H), 7.30 (d, J=8.2Hz, 2H), 4.25 (d, J= 17.0Hz,2H),4.05(d,J=17.0Hz,2H),3.00(s,3H),2.65(s,2H),2.37(s,3H).

[0045] 13 C NMR (101MHz, DMSO) δ201.32,169.12,143.45,135.86,129.42,129.07,62.47,46.74,21.56.

[0046] 11 B NMR (128MHz, DMSO) δ 10.99.

[0047] Example 3

[0048] Synthetic route of compound R3:

[0049]

[0050] Specific synthesis steps:

[0051] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S3), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0052] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0053] S3: After purification with silica gel and elution with eluent (hexane to ethyl acetate in a volume ratio of 1:2), product R3 was obtained with a yield of 48%.

[0054] The NMR data are as follows:

[0055] 1 H NMR (400MHz, DMSO) δ7.90 (d, J=8.7Hz, 2H), 7.51 (d, J=8.6Hz, 2H), 4.26 (d, J= 17.0Hz,2H),4.05(d,J=16.9Hz,2H),3.01(s,3H),2.66(s,2H),1.31(s,9H).

[0056] 13C NMR (101MHz, DMSO) δ201.38,169.15,156.18,135.82,128.90,125.67,62.49,46.79,35.24,31.32.

[0057] 11 B NMR (128MHz, DMSO) δ 11.79.

[0058] Example 4

[0059] Synthetic route of compound R4:

[0060]

[0061] Specific synthesis steps:

[0062] S1: In an air environment, 0.2 mmol of phenylethynylboronic acid methyliminodiacetic acid ester (compound S4), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0063] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction three times with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent.

[0064] S3: After purification with silica gel and elution with eluent (same as in Example 1), product R4 was obtained with a yield of 48%.

[0065] The NMR data are as follows:

[0066] 1 H NMR (400MHz, DMSO) δ7.88(d,J=8.3Hz,2H),7.31(d,J=8.3Hz,2H),4.26(d,J=17.0Hz,2H),4.05(d,J=1 6.9Hz,2H),3.00(s,3H),2.65(s,4H),1.63–1.50(m,2H),1.31(d,J=7.6Hz,2H),0.90(t,J=7.4Hz,3H).

[0067] 13 C NMR (101MHz, DMSO) δ201.38,169.13,148.17,136.09,129.08,128.77,62.49,46.77,35.21,33.22,22.23,14.21.

[0068] 11B NMR (128MHz, DMSO) δ 11.00.

[0069] Example 5

[0070] Synthetic route of compound R5:

[0071]

[0072] Specific synthesis steps:

[0073] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S5), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0074] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction three times with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent.

[0075] S3: After purification with silica gel and elution with eluent (same as in Example 1), product R5 was obtained with a yield of 73%.

[0076] The NMR data are as follows:

[0077] 1 H NMR (400MHz, DMSO) δ7.89(d,J=8.3Hz,2H),7.33(d,J=8.3Hz,2H),4.26(d,J=17.0Hz,2 H), 4.06 (d, J = 17.0Hz, 2H), 3.01 (s, 3H), 2.67 (d, J = 9.0Hz, 4H), 1.20 (t, J = 7.6Hz, 3H).

[0078] 13 C NMR (101MHz, DMSO) δ201.37,169.13,149.53,136.10,129.16,128.25,62.48,46.77,28.59,15.67.

[0079] 11 B NMR (128MHz, DMSO) δ 11.87.

[0080] Example 6

[0081] Synthetic route of compound R6:

[0082]

[0083] Specific synthesis steps:

[0084] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S6), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0085] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0086] S3: After purification with silica gel and elution with eluent (same as in Example 2), product R6 was obtained with a yield of 56%.

[0087] The NMR data are as follows:

[0088] 1 H NMR (400MHz, DMSO) δ7.93(d,J=8.9Hz,1H),6.99(d,J=8.8Hz,1H),4.25(d,J=17.0Hz,1H),4.16–4.00(m,2H),1.35(t,J=7.0Hz,2H).

[0089] 13 C NMR (101MHz, DMSO) δ200.24,169.15,162.61,131.24,114.37,63.93,62.49,46.76,14.99.

[0090] 11 B NMR (128MHz, DMSO) δ 10.97.

[0091] Example 7

[0092] Synthetic route of compound R7:

[0093]

[0094] Specific synthesis steps:

[0095] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S7), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0096] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction three times with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent.

[0097] S3: After purification with silica gel and elution with eluent (same as in Example 2), product R7 was obtained with a yield of 74%.

[0098] The NMR data are as follows:

[0099] 1 H NMR (400MHz, DMSO) δ7.97(d,J=8.7Hz,2H),7.56(d,J=8.6Hz,2H),4.26(d,J=17.0Hz,2H),4.05(d,J=17.0Hz,2H),3.00(s,3H),2.69(s,2H).

[0100] 13 C NMR (101MHz, DMSO) δ200.66,169.05,138.18,136.92,130.87,128.96,62.45,46.74.

[0101] 11 B NMR (128MHz, DMSO) δ 11.26.

[0102] Example 8

[0103] Synthetic route of compound R8:

[0104]

[0105] Specific synthesis steps:

[0106] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S8), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0107] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction three times with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent.

[0108] S3: After purification with silica gel and elution with eluent (same as in Example 3), product R8 was obtained with a yield of 69%.

[0109] The NMR data are as follows:

[0110] 1H NMR (400MHz, DMSO) δ7.77(s,2H),7.41(m,J=7.2Hz,2H),4.26(d,J=17.0Hz,2H),4.05(d,J=17.0Hz,2H),3.00(s,3H),2.67(s,2H),2.37(s,3H).

[0111] 13 C NMR (101MHz, DMSO) δ201.99,169.12,138.37,138.14,133.80,129.29,128.77,126.24,62.48,46.77,21.39.

[0112] 11 B NMR (128MHz, DMSO) δ 11.84.

[0113] Example 9

[0114] Synthetic route of compound R9:

[0115]

[0116] Specific synthesis steps:

[0117] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S9), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0118] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0119] S3: After purification with silica gel and elution with eluent (same as in Example 3), product R9 was obtained with a yield of 72%.

[0120] The NMR data are as follows:

[0121] 1 H NMR (400MHz, DMSO) δ7.94 (d, J=8.9Hz, 2H), 7.01 (d, J=8.9Hz, 2H), 4.25 (d, J= 17.0Hz,2H),4.05(d,J=17.0Hz,2H),3.84(s,3H),3.00(s,3H),2.62(s,2H).

[0122] 13C NMR (101MHz, DMSO) δ200.27,169.15,163.30,131.23,114.01,62.48,55.94,46.76.

[0123] 11 B NMR (128MHz, DMSO) δ 11.98.

[0124] Example 10

[0125] Synthetic route of compound R10:

[0126]

[0127] Specific synthesis steps:

[0128] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S10), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0129] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0130] S3: After purification with silica gel and elution with eluent (same as in Example 1), product R10 was obtained with a yield of 65%.

[0131] The NMR data are as follows:

[0132] 1 H NMR (400MHz, DMSO) δ8.04(dd,J=8.9,5.6Hz,2H),7.31(t,J=8.9Hz,2H),4.26(d,J=17.0Hz,2H),4.05(d,J=17.0Hz,2H),2.99(s,3H),2.68(s,2H).

[0133] 13 C NMR (101MHz, DMSO) δ200.32,169.09,166.56,164.07,134.99,131.84,115.90,62.46,46.74.

[0134] 11 B NMR (128MHz, DMSO) δ 11.79.

[0135] 19F NMR (376MHz, DMSO) δ-107.05 (td, J = 8.9, 4.4Hz).

[0136] Example 11

[0137] Synthetic route of compound R11:

[0138]

[0139] Specific synthesis steps:

[0140] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S11), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0141] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0142] S3: After purification with silica gel and elution with eluent (same as in Example 1), product R11 was obtained with a yield of 28%.

[0143] The NMR data are as follows:

[0144] 1 H NMR(400MHz,DMSO)δ7.57(d,J=7.7Hz,1H),7.48–7.37(m,2H),7.18(d,J=8.2Hz,1H),4 .26(d,J=17.0Hz,2H),4.06(d,J=17.0Hz,2H),3.81(s,3H),2.99(s,3H),2.68(s,2H).

[0145] 13 C NMR (101MHz, DMSO) δ201.50,169.11,159.70,139.72,129.99,121.51,119.20,113.47,62.46,55.71,46.73.

[0146] 11 B NMR (128MHz, DMSO) δ 11.72.

[0147] Example 12

[0148] Synthetic route of compound R12:

[0149]

[0150] Specific synthesis steps:

[0151] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S12), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0152] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0153] S3: After purification with silica gel and elution with eluent (same as in Example 1), product R12 was obtained with a yield of 45%.

[0154] The NMR data are as follows:

[0155] 1 H NMR (400MHz, DMSO) δ7.53–7.38(m,2H),7.11(d,J=8.4Hz,1H),6.98(t,J=7.5Hz,1H),4 .24(d,J=17.0Hz,2H),3.99(d,J=16.9Hz,2H),3.84(s,3H),2.98(s,3H),2.71(s,2H).

[0156] 13 C NMR (101MHz, DMSO) δ204.32,169.10,158.15,133.35,130.46,129.52,120.65,112.70,62.43,56.11,46.83.

[0157] 11 B NMR (128MHz, DMSO) δ 11.83.

[0158] Example 13

[0159] Synthetic route of compound R13:

[0160]

[0161] Specific synthesis steps:

[0162] S1: In an air environment, 0.2 mmol of phenylethynylboronic acid methyliminodiacetic acid ester (compound S13), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0163] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0164] S3: After purification with silica gel and elution with eluent (same as in Example 2), product R13 was obtained with a yield of 70%.

[0165] The NMR data are as follows:

[0166] 1 H NMR (400MHz, DMSO) δ7.69 (d, J=8.9Hz, 1H), 7.43–7.34 (m, 1H), 7.34–7.21 (m, 2H), 4. 26(d,J=17.0Hz,2H),4.04(d,J=17.0Hz,2H),3.01(s,3H),2.64(s,2H),2.36(s,3H).

[0167] 13 C NMR (101MHz, DMSO) δ206.78,169.11,140.54,136.70,131.74,131.09,129.11,126.08,62.47,46.91,20.94.

[0168] 11 B NMR (128MHz, DMSO) δ 11.50.

[0169] Example 14

[0170] Synthetic route of compound R14:

[0171]

[0172] Specific synthesis steps:

[0173] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S14), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0174] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0175] S3: After purification with silica gel and elution with eluent (same as in Example 3), product R14 was obtained with a yield of 79%.

[0176] The NMR data are as follows:

[0177] 1 H NMR (400MHz, DMSO) δ7.89(d,J=8.7Hz,2H),7.71(d,J=8.7Hz,2H),4.26(d,J=17.0Hz,2H),4.05(d,J=16.9Hz,2H),2.99(s,3H),2.68(s,2H).

[0178] 13 C NMR (101MHz, DMSO) δ200.85,169.04,137.24,131.92,131.00,127.37,62.45,46.74.

[0179] 11 B NMR (128MHz, DMSO) δ 11.82.

[0180] Example 15

[0181] Synthetic route of compound R15:

[0182]

[0183] Specific synthesis steps:

[0184] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S15), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 12 h. The reaction was monitored by TLC during the process.

[0185] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0186] S3: After purification with silica gel and elution with eluent (same as in Example 3), product R15 was obtained with a yield of 65%.

[0187] The NMR data are as follows:

[0188] 1H NMR (400MHz, DMSO) δ7.90(d,J=8.3Hz,2H),7.36(d,J=8.4Hz,2H),4.26(d,J=17.0Hz ,2H),4.06(d,J=17.0Hz,2H),3.06–2.89(m,4H),2.66(s,2H),1.22(d,J=6.8Hz,6H).

[0189] 13 C NMR (101MHz, DMSO) δ201.36,169.15,154.02,136.25,129.19,126.81,62.49,46.78,33.93,24.01.

[0190] 11 B NMR (128MHz, DMSO) δ 11.84.

[0191] Example 16

[0192] Synthetic route of compound R16:

[0193]

[0194] Specific synthesis steps:

[0195] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S16), 0.3 mL of acetone, 0.9 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 40 °C for 24 h. The reaction was monitored by TLC during the process.

[0196] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction three times with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent.

[0197] S3: After purification with silica gel and elution with eluent (same as in Example 2), product R16 was obtained with a yield of 39%.

[0198] The NMR data are as follows:

[0199] 1 H NMR (400MHz, DMSO) δ7.09(s,2H),6.73(s,1H),4.26(d,J=17.0Hz,2H),4.06(d,J=16.9Hz,2H),3.80(s,6H),2.98(s,3H),2.66(s,2H).

[0200] 13C NMR (101MHz, CDCl3) δ205.99,173.87,165.56,145.08,111.50,109.88,67.18,60.63,51.42.

[0201] 11 B NMR (128MHz, DMSO) δ 12.01.

[0202] Example 17

[0203] Synthetic route of compound R17:

[0204]

[0205] Specific synthesis steps:

[0206] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S17), 1 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 60 °C for 18 h. The reaction was monitored by TLC during the process.

[0207] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0208] S3: After purification with silica gel and elution with eluent (n-hexane:ethyl acetate = 1:1-1:3), product R17 was obtained with a yield of 18%.

[0209] The NMR data are as follows:

[0210] 1 H NMR (600MHz, DMSO) δ7.55 (dd, J=7.6, 1.7Hz, 1H), 7.54–7.45 (m, 2H), 7.42 (td, J=7.2, 1.6Hz,1H),4.26(d,J=17.0Hz,2H),4.03(d,J=17.0Hz,2H),2.98(s,3H),2.68(s,2H).

[0211] 13 C NMR (151MHz, DMSO) δ204.60,168.99,141.12,132.04,130.60,129.68,129.34,127.64,62.43,46.85.

[0212] 11 B NMR (193MHz, DMSO) δ 11.36.

[0213] Example 18

[0214] Synthetic route of compound R18:

[0215]

[0216] Specific synthesis steps:

[0217] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S18), 1 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 60 °C for 18 h. The reaction was monitored by TLC during the process.

[0218] S1: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0219] S1: After purification with silica gel and elution with eluent (same as in Example 2), product R18 was obtained with a yield of 46%.

[0220] The NMR data are as follows:

[0221] 1 H NMR (400MHz, DMSO) δ7.81(d,J=7.7Hz,1H),7.72(d,J=10.1Hz,1H),7.62–7.52(m,1H),7.46 (t,J=7.6Hz,1H),4.26(d,J=17.0Hz,2H),4.06(d,J=17.0Hz,2H),2.99(s,3H),2.70(s,2H).

[0222] 13 C NMR (101MHz, DMSO) δ200.56,169.07,163.80,161.37,140.55,140.49,131. 05,130.97,125.11,125.08,120.18,119.97,115.54,115.33,62.45,46.71.

[0223] 11 B NMR (128MHz, DMSO) δ 11.62.

[0224] 19 F NMR (376MHz, DMSO) δ-112.81 (td, J = 9.2, 5.4Hz).

[0225] Example 19

[0226] Synthetic route of compound R19:

[0227]

[0228] Specific synthesis steps:

[0229] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S19), 1 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 60 °C for 18 h. The reaction was monitored by TLC during the process.

[0230] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction three times with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent.

[0231] S3: After purification with silica gel and elution with eluent (same as in Example 3), product R19 was obtained with a yield of 45%.

[0232] The NMR data are as follows:

[0233] 1 H NMR (400MHz, DMSO) δ7.99–7.87(m,2H),7.68(d,J=9.2Hz,1H),7.54(t,J=7.9Hz ,1H),4.27(d,J=17.1Hz,2H),4.06(d,J=17.0Hz,2H),3.00(s,3H),2.71(s,2H).

[0234] 13 C NMR (101MHz, DMSO) δ200.52,169.04,140.08,133.90,132.91,130.88,128.58,127.61,62.45,46.72.

[0235] 11 B NMR (128MHz, DMSO) δ 11.41.

[0236] Example 20

[0237] Synthetic route of compound R20:

[0238]

[0239] Specific synthesis steps:

[0240] S1: In an air environment, 0.2 mmol of methyliminodiacetic acid phenylethynylboronic acid (compound S20), 1 mL of trifluoroacetic acid (TFA), and 0.2 mmol of water were added sequentially to a pressure-resistant and sealed reaction tube, and the reaction was stirred at 60 °C for 18 h. The reaction was monitored by TLC during the process.

[0241] S2: After the reaction is complete, ethyl acetate is added to quench the reaction, and the mixture is extracted three times with saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate, and the organic solvent is evaporated.

[0242] S3: After purification with silica gel and elution with eluent (same as in Example 1), product R20 was obtained with a yield of 40%.

[0243] The NMR data are as follows:

[0244] 1 H NMR (600MHz, DMSO) δ8.08(s,1H),7.97(d,J=7.9Hz,1H),7.81(d,J=8.0Hz,1H),7.48(t, J=7.9Hz,1H),4.27(d,J=17.0Hz,2H),4.06(d,J=17.0Hz,2H),2.99(s,3H),2.71(s,2H).

[0245] 13 C NMR (101MHz, DMSO) δ200.48,169.03,140.27,135.80,131.42,131.15,128.01,122.41,62.45,46.72.

[0246] 11 B NMR (128MHz, DMSO) δ 11.43.

[0247] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or basic characteristics. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

[0248] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. An α-boronyl ketone compound, characterized in that, The structural formula is as follows: Wherein, R is a phenyl or a substituted phenyl; The substituent of the substituted phenyl group is C. 1-4 Alkyl, halogen, C 1-2 One or more of the alkoxy groups.

2. The α-boronyl ketone compound as described in claim 1, characterized in that, The substituents of the substituted phenyl group are one or more selected from methyl, ethyl, isopropyl, butyl, halogen, methoxy, and ethoxy.

3. A method for synthesizing α-boronyl ketone compounds as described in claim 1 or 2, characterized in that, The synthesis route is as follows: Includes the following steps: S1: Add methyliminodiacetic acid ester of phenylethynylboronic acid, trifluoroacetic acid and water sequentially into a pressure-resistant and sealed reaction tube, and stir the reaction at 40-60℃ for 12-24h. The reaction is monitored by TLC during the process. S2: After the reaction is complete, ethyl acetate is added to quench the reaction, followed by extraction with saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and evaporation to remove the organic solvent. S3: The product was then purified by silica gel and eluted with eluent to obtain the final product.

4. The method for synthesizing an α-boronyl ketone compound as described in claim 3, characterized in that, In step S1, the molar ratio of phenylethynylboronic acid methyliminodiacetic acid ester to water is 1:1-3.

5. The method for synthesizing an α-boronyl ketone compound as described in claim 3, characterized in that, Step S1 also includes acetone.

6. The method for synthesizing an α-boronyl ketone compound as described in claim 1, characterized in that, The eluent in step S3 is prepared by mixing n-hexane and ethyl acetate in a volume ratio of 1:1-3.

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