Method for removing boron and deuterated aryl boride

Abstract

The method comprises the following steps: by taking stable Ar-BF3-, Ar-Bpin or Ar-B (OH) 2 as a raw material, villiaumite and sulfonic acid or sulfonate as an activating agent and a deuterated solvent as a deuterium source, reacting at a proper temperature in an air or inert gas system, and performing boron-deuteration on an aromatic C-B bond to synthesize a deuterated aromatic compound. The method provides a mild, efficient and high-deuteration-rate synthetic method for the synthesis of a deuterated aromatic compound intermediate in the biological medicine chemical industry. The method has the advantages that the raw materials are simple, easy to obtain and stable, the substrate application range is wide, the method is suitable for various main aromatic borides, operation is easy and convenient, the reaction efficiency is high, green and environment-friendly effects are achieved, and pollution is little, and compared with an existing production process, the method has very remarkable advantages.

Description

Technical Field

[0001] The invention relates to a method for deboronation of an aryl boride, and belongs to the field of chemistry. Background Art

[0002] Deuteration technology advances drug development by replacing hydrogen atoms in molecules to strengthen chemical bonds and slow metabolism. This strategy can optimize pharmacokinetic properties—including extending half-life, reducing dosing frequency, and improving safety—while maintaining the original drug's efficacy. In an era of surging drug development costs, deuteration technology offers a cost-effective solution for molecule optimization that requires minimal structural modification.

[0003] Site-specific deuteration methodologies are crucial. While significant progress has been made in catalytic deuterium exchange, many limitations remain, including the need for directing groups, low selectivity, expensive catalysts, and insufficient deuterium incorporation rates due to reversible reactions (Chin. J. Chem. 2024, 42, 1145-1156). Although site-specific labeling can be achieved through reductive deuteration of functional groups such as alkenes, alkynes, aromatics, nitriles, ketones, amines, phenols, and organic halides, a recent review indicates that the development of milder deuteration strategies remains urgent (Appl. Organomet Chem. 2024, 38, e7602). Although organic boronic acids and their derivatives have become ideal precursors for mild deuteration reactions due to their good stability, low toxicity, and high degree of commercialization (Org. Lett. 2022, 24, 2064-2068; J. Org. Chem. 2021, 86, 1972-1979; Org. Biomol. Chem 2024, 22, 7596-7600; Green Chem. 2020, 22, 6323-6327), existing methods are difficult to be compatible with various boron substrates (boric acid, borate esters, trifluoroborate) at the same time. This requires specific conversion between substrates, which is most likely due to the differences in the interactions of various reagents.

[0004] Therefore, the current deboronation deuteration system is generally only effective for a certain type of aromatic CB bond, and there is no platform system that can deuterate various aromatic CB bonds.

[0005] To overcome this limitation and avoid the specific conversion of boron-containing substrates, the applicant invented a unified mild deuteration platform applicable to various major arylboron compounds, which can deuterate the main substrates of arylboron compounds (including Ar-BF3 - , Ar-BPin, Ar-B(OH)2) realizes a deuteration method that does not require transition metals, is economical, practical, efficient, and has a high deuteration rate. Summary of the Invention

[0006] The technical problem to be solved by the present invention is that the current deboronation deuteration method is generally only effective for a certain type of aromatic CB bond, and there is no platform system that can deuterate various aromatic CB bonds; the current deuteration method has the problems of harsh conditions, high cost, or complex operation. In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0007] A method for deboronation of aryl boride using stable Ar-BF3 - Deuterated aromatic compounds are synthesized by deboronation of aromatic CB bonds using Ar-Bpin or Ar-B(OH)2 as raw materials, fluoride salts and sulfonic acids or sulfonic acid esters as activators, and deuterated solvents as deuterium sources in air or inert gas systems at appropriate temperatures. The chemical formula is as follows:

[0008]

[0009] In the above formulas:

[0010] Preferably, Ar is H, alkyl, aryl, alkoxy, aryloxy, halogen, acyl, hydroxyl, sulfide, nitro, cyano, amide, ester, or the like, substituted phenyl, naphthyl, biphenyl, phenanthrenyl, fluorenyl, benzothiophene, carbazole, or benzofuran;

[0011] Preferably, the fluoride salt is sodium fluoride, potassium fluoride, cesium fluoride, lithium fluoride, potassium bifluoride, or sodium bifluoride;

[0012] Preferably, the amount of the fluoride salt is 0 to 5 equivalents;

[0013] Preferably, the sulfonic acid or sulfonic acid ester is methanesulfonic acid, methyl methanesulfonate, ethyl methanesulfonate, phenyl methanesulfonate, ethanesulfonic acid, methyl ethanesulfonate, ethyl ethanesulfonate, trifluoromethanesulfonic acid, methyl trifluoromethanesulfonate, ethyl trifluoromethanesulfonate, benzenesulfonic acid, methyl benzenesulfonate, ethyl benzenesulfonate, or chloromethyl chlorosulfonate;

[0014] Preferably, the amount of the sulfonic acid or sulfonic acid ester is 0.5 to 5 equivalents;

[0015] Preferably, the deuterated solvent is deuterated methanol, deuterated acetone, deuterated dimethyl sulfoxide, or deuterated water.

[0016] Preferably, the appropriate temperature is 50-100°C;

[0017] Preferably, the gas system is air, argon, or nitrogen.

[0018] The working principle of the present invention: Through long-term and in-depth research, the applicants discovered a method based on the concept of "universal boron atom activation" that converts aromatic boronic acids or boric acid esters into aromatic trifluoroborates in situ via fluoride salts. Furthermore, inexpensive sulfonic acids or sulfonic acid esters are used as multifunctional non-covalent activators. Through the synergistic effect of "boron bond interactions" (i.e., the B...O non-covalent attraction between the electron-deficient boron atom and the lone pair of electrons in the sulfonic acid group) and hydrogen bonds (O...H), a mild, efficient, and high-rate deuteration method for various aromatic boron-containing compounds is achieved. This method has the advantages of simple, readily available, and stable raw materials, a wide range of substrate applications, simple operation, high reaction efficiency, environmental friendliness, and low pollution. Based on this, the inventors completed the present invention.

[0019] The beneficial effects of adopting the above technical solution are:

[0020] 1. Compared with the prior art, the method of the present invention is applicable to the cracking, deboronation and deuteration reaction of various aromatic boron-containing compounds, and has wide applicability.

[0021] 2. The raw materials and reagents used in the method of the present invention are simple and easy to obtain, do not require pre-activation treatment, have good stability, and have no explosion risk.

[0022] 3. The reaction is promoted by intermolecular non-covalent interactions, without the need for catalysts or transition metals. At the same time, the operation is simple, the reaction steps are short, and the yield is high. Compared with existing methods, it is green, environmentally friendly, and has significant economic benefits.

[0023] 4. The deuterated aromatic compound prepared by the present invention has a deuterated rate of over 99%. DETAILED DESCRIPTION

[0024] The present invention will be further described below in conjunction with specific implementation. It should be understood that these embodiments will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, several variations and improvements can be made without departing from the present invention. These all fall within the scope of protection of the present invention. The experimental methods in the following examples where specific conditions are not specified are generally based on conventional conditions, and unless otherwise stated, percentages and parts are calculated by weight. The post-processing methods conventional in the art are all adopted for purification in the examples.

[0025] Example 1

[0026]

[0027] Under argon, compound 3a (0.2 mmol), CD3OD (1 mL), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 18.3 mg of product 4a in a 71% yield with a deuteration rate >95%. 1 H NMR (400MHz, CDCl3) δ7.87 (dd, J=5.9, 3.2Hz, 4H), 7.55-7.48 (m, 3H). 13 C NMR (100MHz, CDCl3) δ133.5, 128.0, 126.0.

[0028] Example 2

[0029]

[0030] Under argon, compound 3a (0.2 mmol), CD3OD (1 mL), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube, followed by heating at 60°C for 24 h. After completion, the reaction solution was concentrated in vacuo and then purified by column chromatography using petroleum ether as the eluent to afford 17.8 mg of product 4a in a 69% yield with a deuteration rate >95%.

[0031] Example 3

[0032]

[0033] Under argon, compound 3a (0.2 mmol), CD3OD (1 mL), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube, followed by heating at 100°C for 24 h. After completion, the reaction solution was concentrated in vacuo and then purified by column chromatography using petroleum ether as the eluent to afford 18.5 mg of product 4a in a 72% yield with a deuteration rate >95%.

[0034] Example 4

[0035]

[0036] Under argon, compound 3a (0.2 mmol), CD3OD (1 mL), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube, followed by heating at 50°C for 24 h. After completion, the reaction solution was concentrated in vacuo and then purified by column chromatography using petroleum ether as the eluent to afford 17.3 mg of product 4a in a 67% yield with a deuteration rate >95%.

[0037] Example 5

[0038]

[0039] Under argon, compound 3a (0.2 mmol), CD3OD (1 mL), and CH3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube, followed by heating at 50°C for 24 h. After completion, the reaction solution was concentrated in vacuo and then purified by column chromatography using petroleum ether as the eluent to afford 16.8 mg of product 4a, with a yield of 65% and a deuterated fraction of 93%.

[0040] Example 6

[0041]

[0042] Under argon, compound 3a (0.2 mmol), CD3OD (1 mL), and CH3SO3H (0.6 mmol) were added sequentially to a 10 mL Schlenk tube, followed by heating at 50°C for 24 h. After completion, the reaction solution was concentrated in vacuo and then purified by column chromatography using petroleum ether as the eluent to afford 17.5 mg of product 4a, with a yield of 68% and a deuterated fraction of 83%.

[0043] Example 7

[0044]

[0045] Under argon, compound 3b (0.2 mmol), CD3OD (1 mL), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 24.2 mg of product 4b, with a yield of 78% and a deuterated fraction of 94%. 1 HNMR (400MHz, CDCl3) δ7.67-7.56(m,4H),7.52-7.41(m,4H),7.40-7.33(m,1H). 13C NMR (100MHz, CDCl3) δ141.3, 128.9, 127.4, 127.3.

[0046] Example 8

[0047]

[0048] Under argon, compound 3c (0.2 mmol), CD3OD (1 mL), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 31.3 mg of product 4c, with a yield of 92% and a deuterated fraction of 94%. 1 HNMR (400MHz, CDCl3) δ7.97 (d, J = 7.7Hz, 2H), 7.59 (d, J = 8.3Hz, 1H), 7.53–7.43 (m, 2H), 7.36 (t, J = 7.5Hz, 2H). 13 C NMR (100MHz, CDCl3) δ156.2, 127.2, 124.3, 122.8, 120.8, 111.8.

[0049] Example 9

[0050]

[0051] Under argon, compound 1b (0.2 mmol), CD3OD (1.0 mL), NaF (0.4 mmol), and CF3SO3CH3 (0.1 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 19.1 mg of product 4b, with a yield of 61% and a deuterated fraction of 94%.

[0052] Example 10

[0053]

[0054] Under argon, compound 1b (0.2 mmol), CD3OD (1.0 mL), NaF (0.4 mmol), and CF3SO3CH3 (0.2 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 22.8 mg of product 4b, with a yield of 73% and a deuterated fraction of 93%.

[0055] Example 11

[0056]

[0057] Under argon, compound 1b (0.2 mmol), CD3OD (1.0 mL), NaF (0.4 mmol), and CF3SO3CH3 (0.4 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 25.6 mg of product 4b, with an 82% yield and a 93% deuteration rate.

[0058] Example 12

[0059]

[0060] Under argon, compound 1b (0.2 mmol), CD3OD (1.0 mL), NaF (0.4 mmol), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 28.8 mg of product 4b, with a yield of 92% and a deuterated fraction of 93%.

[0061] Example 13

[0062]

[0063] Under argon, compound 1b (0.2 mmol), CD3OD (1.0 mL), NaF (0.4 mmol), and CF3SO3CH3 (0.8 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 28.4 mg of product 4b, with a yield of 91% and a deuterated fraction of 92%.

[0064] Example 14

[0065]

[0066] Under argon, compound 1b (0.2 mmol), CD3OD (0.5 mL), NaF (0.4 mmol), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 28.4 mg of product 4b, with a yield of 91% and a deuterated fraction of 87%.

[0067] Example 15

[0068]

[0069] Under argon, compound 1b (0.2 mmol), CD3OD (1.0 mL), KHF2 (0.4 mmol), and PhSO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 19.7 mg of product 4b, with a yield of 63% and a deuterated fraction of 90%.

[0070] Example 16

[0071]

[0072] Under argon, compound 1b (0.2 mmol), CD3OD (1.0 mL), KHF2 (0.4 mmol), and ClSO3CH2Cl (0.6 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 20.9 mg of product 4b, with a yield of 67% and a deuterated fraction of 93%.

[0073] Example 17

[0074]

[0075] Under argon, compound 1b (0.2 mmol), CD3OD (1.0 mL), KHF2 (0.4 mmol), and CH3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 17.5 mg of product 4b, with a yield of 56% and a deuterated fraction of 88%.

[0076] Example 18

[0077]

[0078] Under argon protection, compound 1 (0.2 mmol), CD3OD (0.8 mL), NaF (0.4 mmol), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube, and then heated at 80°C for 24 h. After completion of the reaction, the reaction solution was concentrated in vacuo and then purified by column chromatography using petroleum ether as the eluent to obtain product 4. The yield and deuteration rate of product 4 corresponding to compound 1 used in this example (shown in brackets) are as follows:

[0079]

[0080] Among them, the NMR characterization data of 4d~4ab are:

[0081] 4d: 1 H NMR (400MHz, CDCl3) δ7.56 (dt, J=8.8, 2.9Hz, 4H), 7.45 (d, J=8.0Hz, 2H), 7.19–7.10 (m, 2H). 13 C NMR (100MHz, CDCl3) δ162.6 (d, J = 246.2 Hz), 140.4, 137.5 (d, J = 3.4 Hz), 129.0, 128.8 (d, J = 8.0 Hz), 127.4, 127.2, 115.7 (d, J = 21.6 Hz). 19 F NMR (377 MHz, CDCl3) δ-115.83.

[0082] 4e: 1 H NMR (400 MHz, CDCl3) δ7.54 (dd, J = 14.3, 8.1 Hz, 4H), 7.43 (dd, J = 13.9, 8.0 Hz, 4H). 13 C NMR (100 MHz, CDCl3) δ140.1,139.8,133.5,129.04,129.01,128.5,127.7,127.1. 4f: 1 H NMR (400 MHz, CDCl3) δ7.56 (dd, J=7.6, 2.3 Hz, 4H), 7.50–7.39 (m, 4H). 13 CNMR (100 MHz, CDCl3) δ140.2,140.1,132.0,129.0,128.92,128.88,127.1,121.7.

[0083] 4g:1 H NMR(400 MHz,CDCl3)δ7.56(s,2H),7.46(s,3H),7.39(s,1H),7.26(s,1H),7.17(d,J=10.4 Hz,1H). 13 C NMR(100MHz,CDCl3)δ159.9(d,J=247.6 Hz),135.9,130.9(d,J=3.4 Hz),129.18,129.17(d,J=13.1 Hz),129.16,128.6,127.8,124.4(d,J=3.7Hz),116.1(d,J=22.9 Hz). 19 F NMR(377 MHz,CDCl3)δ-118.11.The s e data wereagreed withlit erature. 2 4h: 1 H NMR(400 MHz,CDCl3)δ7.62(d,J=7.8 Hz,3H),7.46(t,J=7.0 Hz,4H),7.37(t,J=7.3 Hz,2H). 13 C NMR(100 MHz,CDCl3)δ141.3,128.9,127.4,127.3.

[0084] 4i: 1 H NMR(400 MHz,CDCl3)δ7.61(d,J=7.1 Hz,4H),7.46(t,J=7.5 Hz,3H),7.37(d,J=5.3 Hz,2H). 13 C NMR(100 MHz,CDCl3)δ141.3,128.9,127.4,127.3.

[0085] 4j: 1 H NMR(400 MHz,CDCl3)δ7.92–7.83(m,3H),7.51(d,J=4.1 Hz,4H). 13 C NMR(100 MHz,CDCl3)δ133.5,128.0,126.0. 1 4k: 1 H NMR(400 MHz,CDCl3)δ8.17–8.08(m,1H),7.94–7.81(m,1H),7.59–7.49(m,2H),7.45–7.35(m,1H),7.15(dd,J=10.7,7.7 Hz,1H). 13CNMR(100 MHz,CDCl3)δ158.9(d,J=251.4 Hz),134.9(d,J=4.5 Hz),127.6(d,J=3.2Hz),127.0,126.3,125.6(d,J=8.5 Hz),123.8(d,J=16.1Hz),123.3(d,J=21.0 Hz),120.7(d,J=5.2 Hz),109.5(d,J=20.0 Hz). 19 F NMR(377 MHz,CDCl3)δ-123.33.

[0086] 4l: 1 H NMR(400 MHz,CDCl3)δ8.29(d,J=8.4 Hz,1H),7.87(d,J=8.1 Hz,1H),7.66–7.51(m,3H),7.40(d,J=7.3 Hz,1H). 13 C NMR(100 MHz,CDCl3)δ134.7,132.1,130.9,128.3,127.3,127.2,126.8,126.3,125.8,124.5.

[0087] 4m: 1 H NMR(400 MHz,CDCl3)δ8.27(d,J=8.5 Hz,1H),7.91-7.75(m,2H),7.62(t,J=7.6 Hz,1H),7.55(t,J=7.5 Hz,1H),7.33(d,J=7.4 Hz,1H). 13 C NMR(100 MHz,CDCl3)δ134.7,132.1,130.0,128.4,128.0,127.4,127.2,126.8,126.2,122.9.4n: 1 H NMR(400MHz,CDCl3)δ8.01(d,J=7.8 Hz,1H),7.86(d,J=8.8 Hz,1H),7.58–7.45(m,2H),7.38(d,J=6.9Hz,1H),7.33(d,J=7.0 Hz,1H),2.71(s,3H). 13 C NMR(100MHz,CDCl3)δ134.4,133.7,132.7,128.6,126.7,126.5,125.80,125.8,125.70,125.66,124.2,19.5.

[0088] 4o: 1H NMR(400 MHz,DMSO-d6)δ8.82(d,J=8.0 Hz,2H),7.99(d,J=7.7 Hz,2H),7.84(s,1H),7.67(dtd,J=18.6,7.2,1.3 Hz,4H). 13 C NMR(100 MHz,DMSO-d6)δ131.6,129.8,128.5,126.9,126.9,126.8,123.0.

[0089] 4p: 1 H NMR(400 MHz,DMSO-d6)δ7.82(d,J=7.6 Hz,2H),7.54(q,J=3.3,2.3 Hz,2H),7.39–7.25(m,3H),1.42(s,6H). 13 C NMR(100 MHz,DMSO-d6)δ153.2,138.6,127.4,127.0,122.8,120.1,46.4,26.9.

[0090] 4q: 1 H NMR(400 MHz,DMSO-d6)δ6.85(s,3H),3.69(s,6H). 13 CNMR(100 MHz,CDCl3)δ153.8,114.7,55.8.

[0091] 4r: 1 H NMR(400 MHz,CDCl3)δ7.24(d,J=5.9 Hz,2H),6.83(d,J=9.2 Hz,1H),3.79(s,3H). 13 C NMR(100 MHz,DMSO-d6)δ158.1,129.2,124.2,115.7,55.4.The s e datawere agreedwithlit erature.

[0092] 4s: 1 H NMR(400 MHz,CDCl3)δ6.94–6.87(m,3H),3.88(s,6H). 13 C NMR(100 MHz,CDCl3)δ149.0,120.8(d,J=12.1 Hz),111.2(d,J=10.2 Hz),55.9(d,J=1.7 Hz).

[0093] 4t: 1H NMR(400 MHz,CDCl3)δ7.30(s,1H),7.17(d,J=6.7Hz,1H),6.87(d,J=8.3Hz,1H),3.84(s,3H). 13 C NMR(100MHz,CDCl3)δ155.1,130.3,127.8,122.5,121.4,112.2,56.2.4u: 1 H NMR(400 MHz,CDCl3)δ7.35(dt,J=7.7,3.7 Hz,4H),7.11(t,J=7.4 Hz,1H),7.03(d,J=8.5 Hz,4H). 13 C NMR(100MHz,CDCl3)δ157.3,129.9,129.8,123.3,119.0.

[0094] 4v: 1 H NMR(400 MHz,DMSO-d6)δ7.27(d,J=8.5 Hz,2H),6.91(d,J=8.7 Hz,2H),3.94(t,J=6.5 Hz,2H),1.76–1.61(m,2H),1.50–1.36(m,2H),0.93(t,J=7.4 Hz,3H). 13 CNMR(100 MHz,DMSO-d6)δ158.7,129.5,120.4,114.4,66.9,30.8,18.8,13.8.

[0095] 4w: 1 H NMR(400 MHz,CDCl3)δ7.29(d,J=7.9 Hz,2H),6.91(d,J=7.5 Hz,2H),3.93(t,J=6.5 Hz,2H),1.82(q,J=7.2 Hz,2H),1.05(t,J=7.4 Hz,3H).

[0096] 4x: 1 H NMR(400 MHz,CDCl3)δ7.46(d,J=7.3 Hz,2H),7.41(t,J=7.4 Hz,2H),7.33(dd,J=15.6,7.5 Hz,3H),7.00(d,J=8.2 Hz,2H),5.08(s,2H). 13 C NMR(100 MHz,CDCl3)δ158.9,137.2,129.5,128.7,128.1,127.6,121.1,114.9,70.0.

[0097] 4y: 1 H NMR(400 MHz,CDCl3)δ7.45(d,J=7.3 Hz,2H),7.39(t,J=7.4 Hz,2H),7.34(d,J=7.2 Hz,1H),7.10(d,J=11.6 Hz,1H),7.05-6.97(m,2H),5.15(s,2H). 13 C NMR(100 MHz,CDCl3)δ153.1(d,J=245.4 Hz),146.8(d,J=10.8 Hz),136.7,128.8,128.2,127.6,124.3(d,J=3.8Hz),121.6(d,J=6.8Hz),116.3(d,J=18.3Hz),115.8,71.4. 19 FNMR(376MHz,CDCl3)δ-134.09.

[0098] 4z: 1 H NMR(400MHz,CDCl3)δ7.48(d,J=7.3Hz,2H),7.45–7.37(m,3H),7.33(dd,J=8.4,6.1Hz,1H),7.19(dd,J=8.2,1.2Hz,1H),6.97(d,J=8.3Hz,1H),5.17(s,2H). 13 CNMR(100MHz,CDCl3)δ154.3,136.7,130.4,128.7,128.1,127.7,127.2,123.3,121.8,114.1,70.8.

[0099] 4aa: 1 H NMR(400MHz,CDCl3)δ7.90(dd,J=6.6,1.9Hz,1H),7.87–7.79(m,1H),7.43–7.29(m,3H). 13 C NMR(100MHz,CDCl3)δ139.8,139.7,126.4,124.32,124.27,124.0,123.7,122.6.

[0100] 4ab: 1 H NMR(400MHz,CDCl3)δ8.25–8.06(m,2H),7.70–7.53(m,4H),7.44(dd,J=3.3,0.9Hz,4H),7.31(dt,J=8.1,4.2Hz,2H). 13C NMR (100MHz, CDCl3) δ141.0,137.8,123.0,127.6,127.2,126.0,123.4,120.4,120.0,109.9.

[0101] 4ac: 1 H NMR (400MHz, CDCl3) δ7.59-7.51(m,4H),7.43(d,J=8.1Hz,2H),7.01-6.95(m,2H),3.86(s,3H). 13 C NMR (100MHz, CDCl3) δ159.2,140.1,133.9,128.9,128.8,128.3,126.9,114.3,55.5.

[0102] 4ad: 1 H NMR (400MHz, CDCl3) δ7.62–7.55(m,3H),7.50–7.43(m,3H),7.36(dt,J=15.8,7.9Hz,2H). 13 C NMR (100MHz, CDCl3) δ143.2,140.0,134.8,130.1,128.9,128.0,127.43,127.39,127.2,125.4.

[0103] Example 19

[0104]

[0105] Under argon, compound 1a (0.2 mmol), CH3OD (0.8 mL), NaF (0.4 mmol), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube. The mixture was then heated at 80°C for 24 h. After completion, the reaction solution was concentrated in vacuo and purified by column chromatography using petroleum ether as the eluent to afford 18.4 mg of product 4a, with a yield of 72% and a deuterated fraction of 93%.

[0106] Example 20

[0107]

[0108] Under argon protection, compound 2 (0.2 mmol), CD3OD (0.8 mL), NaF (0.4 mmol), and CF3SO3CH3 (0.6 mmol) were added sequentially to a 10 mL Schlenk tube, and then heated at 80°C for 24 h. After completion of the reaction, the reaction solution was concentrated in vacuo and then purified by column chromatography using petroleum ether as the eluent to obtain product 4. The yield and deuteration rate of product 4 corresponding to compound 2 used in this example (shown in brackets) are as follows:

[0109]

[0110] All documents mentioned in the present invention are cited as references in this application, just as each document is cited as reference individually. In addition, it should be understood that after reading the above teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims attached to this application. It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described below (such as in the examples) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described one by one here.

Claims

1. A method for deboronation of aryl boride using stable Ar-BF3 - Deuterated aromatic compounds are synthesized by deboronation of aromatic CB bonds using Ar-Bpin or Ar-B(OH)2 as raw materials, fluoride salts and sulfonic acids or sulfonic acid esters as activators, and deuterated solvents as deuterium sources in air or inert gas systems at appropriate temperatures. The chemical formula is as follows:

2. The method according to claim 1, characterized in that Ar is H, alkyl, aryl, alkoxy, aryloxy, halogen, acyl, hydroxyl, sulfide, nitro, cyano, amide, ester, etc., substituted phenyl, naphthyl, biphenyl, phenanthrenyl, fluorenyl, benzothiophene, carbazole, benzofuran.

3. The method according to claim 1, characterized in that The fluoride salt is sodium fluoride, potassium fluoride, cesium fluoride, lithium fluoride, potassium bifluoride, or sodium bifluoride; preferably, the amount of the fluoride salt is 0 to 5 equivalents.

4. The method according to claim 1, wherein The sulfonic acid or sulfonic acid ester is methanesulfonic acid, methyl methanesulfonate, ethyl methanesulfonate, phenyl methanesulfonate, ethanesulfonic acid, methyl ethanesulfonate, ethyl ethanesulfonate, trifluoromethanesulfonic acid, methyl trifluoromethanesulfonate, ethyl trifluoromethanesulfonate, benzenesulfonic acid, methyl benzenesulfonate, ethyl benzenesulfonate, or chloromethyl chlorosulfonate; preferably, the amount of the sulfonic acid (or its ester) is 0.5 to 5 equivalents.

5. The method according to claim 1, wherein The deuterated solvent is deuterated methanol, deuterated acetone, deuterated dimethyl sulfoxide, or deuterated water.

6. The method according to claim 1, characterized in that The appropriate temperature is 50-100°C.

7. The method according to claim 1, characterized in that The gas system is air, argon and nitrogen.

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