Synthesis method of acyl borane compound

Abstract

The invention discloses a synthesis method of an acyl borane compound, which is characterized in that the acyl borane compound is obtained through a cross dehydrogenation coupling (CDC) reaction of an aldehyde / alcohol compound and a coordination borane compound in a direct and mild manner with a brand-new concept. On the other hand, the types of rare compounds of the acyl borane compounds are enriched, a series of application and conversion researches of the acyl borane compounds are developed, and it is shown that the acyl borane compounds can be used as fine chemical engineering intermediates to be applied to construction of various practical molecular structures.

Description

Technical Field

[0001] This application belongs to the field of fine chemical intermediate synthesis technology, specifically relating to a method for synthesizing acylborane compounds. Background Technology

[0002] Acylboron compounds are highly valuable molecular entities with wide applications in organic synthesis, materials science, and medicinal chemistry. They can rapidly form amide bonds, providing a versatile tool for protein coupling and the modification of peptides, proteins, and polymers. Previously, acylboron compounds were considered unstable reaction intermediates. However, in 2007, Nozaki, Yamashita, and colleagues first isolated acylboron esters via the reaction of boron anions with acyl chlorides. Since then, groups such as Molander, Bode, Mankad, and Yudin have reported the synthesis of various acylboron esters, including potassium acyltrifluoroborate and acyl N-methyliminodiacetic acid (MIDA) borate, significantly improving the stability and synthetic practicality of acylboron chemistry. In contrast, reports on acylboranes remain very rare, and their broader application exploration is hindered by significant synthetic challenges. While the traditional synthesis of acylboranes via the addition of boron anions to carbonyl derivatives using a transiently masked method is valuable, it is extremely sensitive to moisture and requires the use of strong organolithium bases (J. Org. Chem. 1994, 59, 6753-6759. Angew. Chem., Int. Ed. 2010, 49, 9166-9169). Recently, copper-catalyzed aldehyde C–H borylation reactions, using NHC•BH2–Bpin as a reagent, have enabled the synthesis of NHC-coordinated acylboranes (J. Am. Chem. Soc. 2025, 147, 18397-18405). Recently, a nickel-catalyzed C(acyl)–B(sp³) cross-coupling strategy has been developed, which can directly prepare phosphine-coordinated acylboranes from carboxylic acids and coordinated borane species (Angew. Chem. Int. Ed. 2025, e16826, DOI: 10.1002 / anie.202516826). Despite these significant advances, the direct condensation of readily available aldehydes with stable coordinated boranes has not been systematically studied, which represents a promising new route for the synthesis of acylboranes.

[0003] This invention reports for the first time a cross-dehydrogenation coupling (CDC) reaction between an aldehyde and a coordinated borane, yielding acylborane compounds in a direct, mild, and novel manner. This synthetic strategy not only overcomes the limitations of traditional routes but also provides acylborane compounds that are easily converted into various subsequent forms. Summary of the Invention

[0004] The purpose of this invention is to provide a method for synthesizing acylborane compounds. This method involves a cross-dehydrogenation coupling (CDC) reaction between an aldehyde / alcohol compound and a coordinated borane compound to obtain acylborane compounds in a direct, mild, and novel manner. Furthermore, this invention enriches the variety of this rare class of acylborane compounds and has facilitated a series of application and transformation studies of acylborane compounds, demonstrating their potential use as fine chemical intermediates in the construction of various practical molecular structures.

[0005] A method for synthesizing acylborane compounds according to the present invention is characterized by comprising the following steps: An aldehyde of Formula 1 or an alcohol of Formula 1', a coordinated borane compound of Formula 2, an auxiliary agent, and a solvent are added sequentially to a reactor. The reactor is then placed under an inert atmosphere and irradiated with blue LED light at room temperature with stirring. After the reaction is complete, the mixture is purified to obtain an acylborane compound of Formula 3. The reaction formula is as follows: ; In the above reaction formula, Ar represents substituted or unsubstituted C. 6-20 aryl, substituted or unsubstituted C 2-20 Heteroaryl groups. The substituents are selected from halogens, C... 1-6 Alkyl, C 1-6 Alkoxy, (C 1-6 Alkyl)3Si-, C 6-20 Aryl, C 2-6 alkynyl group, C 1-6 Alkyl-SO2-, (C 1-6 alkyl)2P(O)-, (C 1-6 alkoxy)2P(O)-, R1R2B-, -CN, C 1-6 Haloalkyl, C 1-6 Alkoxycarbonyl, C 3-8 Cycloalkoxycarbonyl; the C 6-20 Aryl, C 2-6 The alkynyl group can be optionally replaced by halogens, C 1-6 Alkyl, C 1-6 Alkoxy, (C 1-6 Alkyl)3Si-substituted. R1 and R2 are selected from C. 1-6 alkoxy groups, or R1, R2 together with B atoms, constitute unsubstituted or C-substituted groups. 1-6 Alkyl-substituted five- to six-membered cyclic borate esters.

[0006] R is selected from methyl or ethyl; preferably methyl.

[0007] Preferably, Ar represents substituted or unsubstituted phenyl, naphthyl, substituted or unsubstituted pyridyl, furanyl, or thiophene. The substituent is selected from fluorine, chlorine, bromine, iodine, methyl, methoxy, trimethylsilyl, phenyl, ethynyl, methanesulfonyl, Me₂P(O)⁻, (MeO)₂P(O)⁻, (MeO)₂B, (EtO)₂B, etc. -CN, trifluoromethyl, methoxycarbonyl, cyclohexyloxycarbonyl , The phenyl and ethynyl groups in the substituents may optionally be replaced by fluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, or trimethylsilyl groups.

[0008] Most preferably, Ar represents a substituted or unsubstituted phenyl group; wherein the substituent is selected from fluorine, chlorine, bromine, iodine, methyl, methoxy, trimethylsilyl, phenyl, trimethylsilylethynyl, methanesulfonyl, (MeO)₂P(O)⁻, -CN, trifluoromethyl, methoxycarbonyl, cyclohexyloxycarbonyl , .

[0009] According to the aforementioned synthesis method of the present invention, the auxiliary agent is a persulfate or a silver salt; wherein the persulfate is selected from (NH4)2S2O8, Na2S2O8, and K2S2O8, preferably (NH4)2S2O8, and the silver salt is selected from silver carbonate, silver bromide, and silver nitrate, preferably silver bromide.

[0010] According to the aforementioned synthesis method of the present invention, the solvent is acetonitrile, methanol, or a mixed solvent of acetonitrile and water, preferably a mixed solvent of acetonitrile and water. The volume ratio of acetonitrile to water in the mixed solvent of acetonitrile and water is 1:3 to 3:1, preferably 1:2. The amount of solvent used is such that the concentration of compound of formula 1 or formula 1' is 0.01 to 1 mol / L, preferably 0.1 to 0.15 mol / L.

[0011] According to the aforementioned synthesis method of the present invention, the inert atmosphere is a nitrogen atmosphere or an argon atmosphere, preferably an argon atmosphere.

[0012] According to the aforementioned synthesis method of the present invention, the power of the blue LED is 5~100W, preferably 18~50W.

[0013] According to the aforementioned synthesis method of the present invention, the molar ratio of the aldehyde represented by Formula 1 or the alcohol represented by Formula 1', the coordinated borane compound represented by Formula 2, and the auxiliary agent is 1:(1~5):(1~5), preferably 1:3:(3~4).

[0014] According to the aforementioned synthesis method of the present invention, the reaction time of the room temperature stirring reaction is 4 to 24 hours, preferably 8 to 12 hours.

[0015] According to the aforementioned synthesis method of the present invention, the purification process is performed as follows: The reaction solution was quenched with NaHCO3, extracted, the organic phase was dried with anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the acylborane compound shown in Formula 3.

[0016] Compared with existing technologies, the method of the present invention has the following significant advantages: (1) This invention discloses for the first time the cross-dehydrogenation coupling (CDC) reaction of aldehyde / alcohol compounds with coordinated borane compounds to obtain acylborane compounds in a direct, mild and novel manner.

[0017] (2) This invention enriches the variety of rare compounds in this class of acylborane compounds, which can be used as fine chemical intermediates to construct a variety of practical molecular structures. Detailed Implementation

[0018] The present invention will be further described in detail below with reference to specific embodiments. Unless otherwise specified, the methods used herein are conventional methods in the art, and the reagents used are obtained through conventional commercial channels and / or prepared by methods known in the art.

[0019] Example 1 of preparation of coordinated borane compounds ; Under argon protection, a phosphine ligand (1.0 equivalent) was dissolved in THF (1.0 M), and a 1.0 M THF solution of a borane-tetrahydrofuran complex (1.2 equivalent) was slowly added dropwise at 0 °C. The reaction mixture was stirred overnight at 0 °C. MeOH (1.2 equivalent) was then added to quench the reaction, and the mixture was concentrated under reduced pressure. The crude product was purified by rapid silica gel column chromatography to obtain the phosphine-borane coordinated borane product.

[0020] Example 2 of preparation of coordinated borane compounds ; Ammonia-borane (310 mg, 10 mmol) was added to a round-bottom flask, and a water-cooled reflux condenser was installed. After purging the system with a stream of nitrogen, anhydrous THF (2.5 mL) was added using a syringe technique. With stirring, phosphine ligand (10 mmol) was slowly added dropwise at room temperature. The reaction mixture was then heated to reflux, and the reaction progress was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, and the solution was transferred to another clean, dry 25 mL round-bottom flask using a tube. The solvent was removed under reduced pressure, and the crude product was purified by column chromatography to obtain the phosphine-borane coordination product.

[0021] Reaction condition optimization experiment Using benzaldehyde (Formula 1a) and the trimethyl phosphite borane complex (Formula 2a) as template substrates, the effects of different synthetic conditions on the yield of the acylborane compound (Formula 3aa) were investigated. The reaction formulas are as follows: ; ; Taking Example 1 as an example, the typical experimental procedure is as follows: In a Schlenk tube, 1a (0.2 mmol), 2a (0.6 mmol, 3.0 equivalents), (NH4)2S2O8 (3 equivalents), and MeCN:H2O (1:2, 0.13 M) were added sequentially. The tube was then purged three times with argon, placed under an 18 W blue LED lamp (approximately 5 cm from the light source), cooled with a fan, and stirred at room temperature for 12 h. After the reaction was complete, the reaction was quenched with NaHCO3. The organic phases were combined, dried over Na2SO4, and concentrated under reduced pressure. The solvent was removed under vacuum, and the residue was purified by silica gel column chromatography (n-hexane / ethyl acetate) to give product 3aa (42.0 mg, 87%). This product was a yellow oily liquid. 1 H NMR (400 MHz, Chloroform- d ) δ (ppm) 8.03 – 7.99 (m, 2H), 7.46 – 7.37 (m, 3H), 3.80 (d, J = 10.8 Hz, 9H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 143.0, 131.5, 127.9, 127.7 (d, J =3.6 Hz), 53.6 (d, J = 4.0 Hz); 11 B NMR (128 MHz, Chloroform- d) δ (ppm) -31.53(d, J = 122.0 Hz); 31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 106.61 – 102.97 (m).

[0022] Under the standard reaction conditions of Example 1, the substrate universality of this synthetic strategy was further investigated, and the results are as follows: ; a Reaction conditions: 1a (0.2 mmol), 2a (3 equiv.), (NH4)2S2O8 (3 equiv.), MeCN:H2O (1:2, 0.13 M), 18 W blue LEDs, argon, room temperature, 12 h. b Reaction conditions: 1a (0.2 mmol), 2a (3 equiv.), (NH4)2S2O8 (4 equiv.), MeCN:H2O (1:2, 0.13 M), 18 W blue LEDs, argon, room temperature, 12 h.

[0023] Structural characterization of the product: 3ba: R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 7.92 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8. Hz, 2H), 3.80 (d, J = 10.8 Hz, 8H), 2.37 (s, 3H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 141.9, 140.8, 128.6,127.9 (d, J = 3.8 Hz), 53.6 (d, J = 4.2 Hz), 20.5; 11 B NMR (128 MHz, Chloroform- d ) δ (ppm) -31.55 (d, J = 119.7 Hz);31 P NMR (162 MHz, Chloroform- d ) δ (ppm)107.35 – 102.74 (m)。

[0024] 3ca:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 11 H NMR (400 MHz, Chloroform- d ) δ (ppm) 8.12 (d, J = 6.8 Hz, 2H), 7.66 (d, J = 8.2 Hz, 4H), 7.47-7.35 (m,3H), 3.83 (d, J = 11.1 Hz, 9H); 13 C NMR (100 MHz, Chloroform-d) δ (ppm) 144.0,141.8, 140.5, 128.7, 128.3 (d, J = 3.5 Hz), 127.6, 127.2, 126.7, 53.6 (d, J =3.9 Hz); 11 B NMR (128 MHz, Chloroform- d ) δ (ppm) -31.43 (d, J = 122.9 Hz); 31 PNMR (162 MHz, Chloroform- d ) δ (ppm) 107.59 – 101.94 (m).。

[0025] 3da:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 8.00 – 7.96 (m, 2H), 7.60 – 7.55 (m, 2H), 3.81 (d, J = 10.8 Hz, 9H),0.27 (s, 9H); 13 C NMR (100 MHz, Chloroform- d) δ (ppm) 144.9, 133.1, 126.8,126.8,, 53.7 (d, J = 4.0 Hz), -1.24; 11 B NMR (128 MHz, Chloroform- d ) δ (ppm) -31.62 (d, J = 130.3 Hz); 31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 107.64 – 102.37(m)。

[0026] 3ea:R f = 0.4 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 7.92 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 3.80 (d, J = 11.2Hz, 9H), 0.24 (s, 9H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 142.3, 131.6,127.6, 126.1, 96.3, 53.7, -0.1; 11 B NMR (128 MHz, Chloroform- d ) δ (ppm) -31.59(d, J = 108.8 Hz); 31 P NMR (162 MHz, Chloroform- d ) δ (ppm) δ 104.22 (d, J = 149.0Hz)。

[0027] 3fa:R f = 0.2 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (500 MHz, Chloroform- d )δ (ppm) 8.13 (d, J= 8.4 Hz, 2H), 7.96 (d, J = 8.4 Hz, 2H), 3.81 (d, J = 10.8Hz, 9H), 3.04 (s, 3H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 146.7, 142.3,128.5 (d, J = 3.6 Hz), 126.7, 53.7 (d, J = 4.3 Hz), 44.4; 11 B NMR (128 MHz,Chloroform- d ) δ (ppm) -31.52 (d, J = 123.5 Hz) ; 31 P NMR (162 MHz, Chloroform- d )δ (ppm) 105.36 – 100.54 (m)。

[0028] 3ga:R f = 0.5 (PE / EA = 1 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 8.08 – 8.03 (m, 2H), 7.86 – 7.80 (m, 2H), 3.80 (d, J = 11.2 Hz, 9H),3.74 (d, J = 11.2 Hz, 6H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 131.8 (d, J =10.1 Hz), 130.4, 128.5, 127.6 (dd, J = 3.5, 3.5 Hz), 53.7 (d, J = 4.2 Hz), 52.7(d, J = 6.6 Hz); 11 B NMR (128 MHz, Chloroform- d ) δ (ppm) -31.56 (d, J = 124.9Hz);31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 103.69 (d, J = 158.4 Hz), 21.79.HRMS m / z (ESI) calcd for C 12 H 22 BO7P2([M+H] + ) 351.0928, found 351.0928. 3ha:R f = 0.2 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 7.98 (d, J = 8.1 Hz, 2H), 7.84 (d, J = 8.1 Hz, 2H), 3.80 (d, J = 11.0Hz, 9H), 1.34 (s, 12H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 144.7, 133.7,126.8 (d, J = 3.1 Hz), 86.1, 53.6 (d, J = 4.0 Hz), 24.8; 11 B NMR (128 MHz,Chloroform- d ) δ (ppm) -30.82, -31.59 (d, J = 121.6 Hz); 31 P NMR (162 MHz,Chloroform- d ) δ (ppm) 104.66 (d, J = 172.0 Hz).。

[0029] 3ia:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 8.05 (d, J= 8.4 Hz, 2H), 7.70 (d, J = 8.0 Hz, 2H), 3.81 (d, J = 10.8Hz, 9H); 13 C NMR (125MHz, Chloroform- d ) δ (ppm) 145.3, 132.1, 128.1 (d, J = 3.6Hz) 118.7, 114.5, 53.7 (d, J = 4.3 Hz); 11 B NMR (128 MHz, Chloroform- d ) δ (ppm)-31.51 (d, J = 125.7 Hz); 31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 105.47 –100.78 (m)。

[0030] 3ja:R f = 0.2 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (500 MHz, Chloroform- d )δ (ppm) 8.08 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.0 Hz, 2H), 3.81 (d, J = 11.2Hz, 9H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 145.2, 132.7 (q, J = 32.0 Hz),127.9 (d, J = 3.2 Hz), 125.0 (q, J = 3.8 Hz), 124.0 (q, J = 270.9 Hz), 53.7 (d, J = 4.0 Hz) ; 11 B NMR (128 MHz, Chloroform- d ) δ (ppm) -31.56 (d, J = 124.2 Hz);31 PNMR (162 MHz, Chloroform- d ) δ (ppm) 105.87 – 101.35 (m). 19 F NMR (376 MHz,Chloroform- d ) δ (ppm) -62.68。

[0031] 3ka:R f = 0.5 (PE / EA = 2 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 8.06 – 7.99 (m, 4H), 3.89 (s, 3H), 3.79 (d, J = 11.2 Hz, 9H); 13 C NMR(100 MHz, Chloroform- d ) δ (ppm) 166.8, 146.2, 132.2, 129.3, 127.5 (d, J = 3.5Hz), 53.64 (d, J = 4.2 Hz), 52.1 183.4, 167.0, 146.0, 132.4, 129.5, 127.7 (d, J = 1.2 Hz), 53.8 (d, J = 1.6 Hz), 52.28.; 11 B NMR (128 MHz, Chloroform- d ) δ (ppm)-31.52 (d, J = 117.4 Hz); 31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 106.40 –101.06 (m). 。

[0032] 3la:R f = 0.3 (PE / EA = 10 : 1); Yellow oil; 1 H NMR (500 MHz, Chloroform- d ) δ (ppm) 8.14 – 7.96 (m, 2H), 7.04 (t, J= 8.8 Hz, 2H), 3.80 (d, J = 10.8 Hz,9H); 13 C NMR (125 MHz, Chloroform- d ) δ (ppm) 164.7 (d, J = 250.1 Hz), 139.6,130.2 (dd, J = 3.6, 3.6 Hz), 114.7 (d, J = 21.3 Hz), 53.6 (d, J = 4.0 Hz) ; 11 BNMR (128 MHz, Chloroform- d ) δ (ppm) -31.63 (d, J = 123.6 Hz); 31 P NMR (162 MHz,Chloroform- d ) δ (ppm) 106.23 – 102.21 (m); 19 F NMR (376 MHz, Chloroform- d ) δ(ppm) -108.67。

[0033] 3ma:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 HNMR (400 MHz, Chloroform- d )δ (ppm) 7.93 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.8 Hz, 2H), 3.80 (d, J = 10.8Hz, 9H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 141.3, 137.6, 129.2 (d, J = 3.5Hz), 128.1, 53.6 (d, J = 4.2 Hz); 11 B NMR (128 MHz, Chloroform- d ) δ (ppm) -31.67(d, J = 124.0 Hz) ;31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 106.26 – 101.84 (m). 。

[0034] 3na:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 HNMR (400 MHz, Chloroform- d )δ (ppm) 7.86 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 3.79 (d, J = 11.2Hz, 9H), 2.70 – 1.98 (m, 2H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 141.6,131.1, 129.4 (d, J =3.8 Hz), 126.4, 53.7 (d, J = 4.0 Hz); 11 B NMR (128 MHz,Chloroform- d ) δ (ppm) -31.68 (d, J = 125.0 Hz) ; 31 P NMR (162 MHz, Chloroform- d )δ (ppm) 105.09, 104.41, 103.57, 102.89。

[0035] 3oa:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 7.76 (d, J = 9.0 Hz, 2H), 7.22 (d, J = 6.6 Hz, 2H), 3.74 (d, J = 11.1Hz, 9H), 2.32 (s, 3H); 13 C NMR (100 MHz, Chloroform- d) δ (ppm) 137.5, 132.3,128.1, 127.9, 125.2, 125.2, 53.7 (d, J = 4.0 Hz), 21.8; 11 B NMR (128 MHz,Chloroform- d ) δ (ppm) -31.48 (d, J = 120.3 Hz); 31 P NMR (162 MHz, Chloroform- d )δ (ppm) 107.21 – 102.86 (m)。

[0036] 3pa:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 7.79 (d, J = 9.1 Hz, 1H), 7.33 – 7.07 (m, 3H), 3.74 (d, J = 11.0 Hz,9H), 2.40 (s, 3H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 135.2, 131.2, 130.5,130.5, 129.6, 125.2, 53.6 (d, J = 3.4 Hz), 20.5; 11 B NMR (128 MHz, Chloroform- d )δ (ppm) -30.58 (d, J = 108.8 Hz) ; 31 P NMR (162 MHz, Chloroform- d ) δ (ppm)105.81 – 101.60 (m)。

[0037] 3qa:R f = 0.5 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 7.84 (d, J= 2.0 Hz, 2H), 7.42 (t, J = 2.0 Hz, 1H), 3.80 (d, J = 11.2Hz, 9H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 145.0, 135.0, 131.1, 126.4 (d, J = 3.7 Hz), 53.8 (d, J = 4.2 Hz), 20.5; 11 B NMR (128 MHz, Chloroform- d ) δ (ppm)-31.80 (d, J = 124.9 Hz) ; 31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 105.33 –100.94 (m)。

[0038] 3ra:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 8.25 (s, 1H), 8.17 (d, J = 8.8 Hz, 1H), 6.98 (d, J = 8.8 Hz, 1H), 3.92(s, 3H), 3.79 (d, J = 11.2 Hz, 9H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm)159.8, 135.8, 133.4, 127.2, 123.6 (q, J = 271.0 Hz), 117.9 (q, J = 30.8 Hz),110.9, 56.0, 53.6 (d, J = 0.4 Hz); 11 B NMR (128 MHz, Chloroform- d ) δ (ppm) -31.78 (d, J = 121.3 Hz);31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 106.41 – 101.43(m); 19 F NMR (376 MHz, Chloroform- d ) δ (ppm) -62.47.。

[0039] 3sa:R f = 0.2 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 8.07 – 8.01 (m, 4H), 4.96 – 4.88 (m, 1H), 3.80 (d, J = 11.2 Hz, 9H),2.17 – 1.85 (m, 3H), 1.71 (d, J = 14.0 Hz, 2H), 1.60 – 1.50 (m, 2H), 1.18 –1.04 (m, 2H), 0.91 (t, J = 5.6 Hz, 6H), 0.77 (d, J = 7.2 Hz, 3H); 13 C NMR (100MHz, Chloroform- d ) δ (ppm) 165.8, 145.7, 133.0, 129.3, 127.5, 75.0, 53.7 (d, J = 4.2 Hz), 46.7, 40.9, 34.9, 32.0, 26.5, 24.2, 22.0, 19.8, 16.5; 11 B NMR (128MHz, Chloroform- d ) δ (ppm) -31.49 (d, J = 90.2 Hz) ; 31 P NMR (162 MHz,Chloroform- d ) δ (ppm) 103.90 (d, J = 170.3 Hz). HRMS m / z (ESI) calcd forC 21 H 35 BO6P([M+H]+ ) 425.2259, found 425.2260. 3ta:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 8.10 – 8.01 (m, 4H), 5.85 (s, 1H), 4.72 (d, J = 6.4 Hz, 4H), 3.82 (d, J = 10.8 Hz, 9H), 2.17 (d, J = 8.4 Hz, 3H), 2.04 – 1.98 (m, 1H), 1.91 – 1.84 (m,1H), 1.74 (s, 3H), 1.65 (s, 1H), 1.58 – 1.48 (m, 1H); 13 C NMR (100 MHz,Chloroform- d ) δ (ppm) 166.2, 149.6, 132.6, 132.5, 129.4, 127.6, 127.6, 125.8,108.8, 70.0, 53.7 (d, J = 4.0 Hz), 40.8, 30.5, 27.3, 26.4, 20.7; 11 B NMR (128MHz, Chloroform- d ) δ (ppm) -31.42 (d, J = 62.2 Hz); 31 P NMR (162 MHz,Chloroform- d ) δ (ppm) 103.87 (d, J = 169.5 Hz)。

[0040] 3ua:R f = 0.3 (PE / EA = 5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d )δ (ppm) 8.10 – 8.01 (m, 4H), 5.13 – 5.08 (m, 1H), 3.80 (d, J= 11.2 Hz, 9H),2.50 – 2.41 (m, 1H), 2.16 – 2.09 (m, 1H), 1.84 – 1.75 (m, 1H), 1.72 (t, J =4.4 Hz, 1H), 1.44 – 1.35 (m, 1H), 1.34 – 1.26 (m, 1H), 1.14 – 1.08 (m, 1H), 0.95 (s, 3H), 0.90 (s, 6H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 166.5,145.5, 133.0, 129.3, 127.5, 80.6, 53.6 (d, J = 4.0 Hz), 50.0, 47.8, 44.9,36.8, 28.0, 27.3, 19.7, 18.8, 13.5; 11 B NMR (128 MHz, Chloroform- d ) δ (ppm) -31.45 (d, J = 94.8 Hz); 31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 103.85 (d, J =164.1 Hz).

[0041] Application Example 1 ; A dried 10 mL Schlenk tube (with a built-in magnetic stir bar and PTFE screw cap) was sequentially loaded with acylborane (24.2 mg, 0.1 mmol, 1.0 equivalent), 4-iodoanisole (46.8 mg, 0.2 mmol, 2.0 equivalent), Pd(dppf)Cl2 (7.3 mg, 0.01 mmol, 10 mol%), Cs2CO3 (162.9 mg, 0.5 mmol, 5.0 equivalent), and 1,4-dioxane (1 mL). The reaction mixture was stirred at 80 °C for 12 hours under nitrogen protection. After cooling to room temperature, the mixture was dried over anhydrous Na2SO4, filtered through a diatomaceous earth filter, washed with ethyl acetate, and concentrated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane / ethyl acetate) to give product 4 (10.2 mg, 48%). White solid; 1 H NMR (400 MHz, Chloroform-d ) δ (ppm) 7.86 – 7.81 (m, 2H), 7.80 – 7.72 (m, 2H), 7.03 – 6.94(m, 2H), 3.88 (s, 3H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 195.5, 163.2,138.2, 132.5, 131.9, 130.1, 129.7, 128.1, 113.5, 55.5.

[0042] Application Example 2 ; A dried 10 mL Schlenk tube (with a built-in magnetic stir bar and PTFE screw cap) was sequentially filled with potassium tert-butoxide (13.4 mg, 0.12 mmol, 1.2 equivalents) and trimethylsulfonium iodide (26.4 mg, 0.12 mmol, 1.2 equivalents). DMSO (3.5 mL / mmol) was slowly added dropwise using a syringe, stirring until the solid was completely dissolved. Subsequently, a solution of the reactant (1.0 equivalent) dissolved in DMSO (2.0 mL / mmol) was slowly added dropwise to the above system, and stirring was continued at room temperature for 4 hours. After the reaction was complete, the mixture was dried over anhydrous Na₂SO₄, filtered through a diatomaceous earth filter, washed with ethyl acetate, and concentrated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane / ethyl acetate) to give product 5 (15.1 mg, 59%). f = 0.3 (PE / EA =5 : 1); Yellow oil; 1 H NMR (400 MHz, Chloroform- d ) δ (ppm) 8.03 – 8.00 (m,2H), 7.49 – 7.45 (m, 1H), 7.43 – 7.38 (m, 2H), 3.73 (d, J = 10.4 Hz, 9H), 2.37(d, J = 21.2 Hz, 2H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 137.4, 131.8,129.6, 128.0, 53.4 (d, J = 4.7 Hz), 26.4; 11 B NMR (128 MHz, Chloroform-d ) δ(ppm) -34.26 (d, J = 105.0 Hz); 31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 109.34 –106.11 (m).

[0043] Application Example 3 ; A dried 10 mL Schlenk tube (with a built-in magnetic stir bar and PTFE screw cap) was sequentially filled with acylborane (24.2 mg, 0.1 mmol, 1.0 equivalent), N-chlorosuccinimide (NCS, 29.4 mg, 0.22 mmol, 2.2 equivalent), and 1,4-dioxane (2 mL). The mixture was stirred at room temperature for 30 min under nitrogen protection. Then, 100 μL of degassed H₂O was added, and stirring continued for another 30 min under nitrogen at room temperature. Next, 4-iodoanisole (28.1 mg, 0.12 mmol, 1.2 equivalent), Pd(dppf)Cl₂ (7.3 mg, 0.01 mmol, 10 mol%), and Cs₂CO₃ (162.9 mg, 0.5 mmol, 5.0 equivalent) were added. The resulting mixture was stirred at 110 °C for 12 h under nitrogen protection. After cooling to room temperature, the sample was dried over anhydrous Na₂SO₄, filtered through a diatomaceous earth filter, washed with ethyl acetate, and concentrated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane / ethyl acetate) to give product 6 (9.6 mg, 52%); R f = 0.3 (PE / EA = 100 : 1);Yellow oil; 1 H NMR (400 MHz, Chloroform- d ) δ (ppm) 7.55 (t, J = 8.0 Hz, 4H), 7.42 (t, J = 8.0 Hz, 2H), 7.31 (t, J = 7.2 Hz, 1H), 6.99 (d, J =9.2 Hz, 2H), 3.86 (s, 3H); 13 C NMR (100 MHz, Chloroform- d) δ (ppm) 159.1, 140.8, 133.8,128.7, 128.1, 126.7, 126.6, 114.2, 55.3.

[0044] Application Example 4 ; A dried 10 mL Schlenk tube (with a built-in magnetic stir bar and PTFE screw cap) was filled with acylborane (24.2 mg, 0.1 mmol, 1.0 equivalent) and methanol (2 mL). p-Toluenesulfonylhydrazine (28.1 mg, 0.11 mmol, 1.1 equivalent) was slowly added, and the mixture was stirred at room temperature for 4 hours. After the reaction was complete, methanol was removed by vacuum distillation. The residue was purified by silica gel column chromatography (n-hexane / ethyl acetate) to give product 7 (11.5 mg, 62%). f = 0.3 (PE / EA = 2 : 1);Yellow solid; 1H NMR (400 MHz, Chloroform- d ) δ (ppm) 8.26 (s, 1H), 7.85 (d, J = 8.0 Hz, 2H), 7.70 – 7.65 (m, 2H), 7.30 – 7.22 (m, 5H), 3.59 (d, J = 10.8 Hz, 9H), 2.35 (s, 3H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 143.3, 142.7, 136.2,129.2, 128.0, 127.7, 127.6, 127.4, 53.6 (d, J = 6.0 Hz), 21.4.; 11 B NMR (128MHz, Chloroform- d ) δ (ppm) -38.58 (d, J = 94.8 Hz); 31 P NMR (162 MHz, Chloroform- d ) δ (ppm) 103.89 (d, J = 174.2 Hz).

[0045] Application Example 5 ; In a round-bottom flask, the corresponding acylborane (24.2 mg, 0.1 mmol, 1.0 equivalent) was dissolved in 1 mL of THF / water buffer (1:1, pH = 3, 25 mM; this buffer was prepared by dissolving 4.48 g (21.35 mmol) of citrate monohydrate and 1.07 g (3.64 mmol) of sodium citrate dihydrate in 1 L of distilled water, and the final pH was adjusted with 0.1 M NaOH and HCl solution). An amine (0.15 mmol, 1.5 equivalent) and 1,3-dichloro-5,5-dimethylhydantoin (DCH, 39.4 mg, 0.2 mmol, 2.0 equivalent) were added sequentially, and the mixture was stirred at room temperature for 12 hours. The reaction solution was quenched with saturated Na₂S₂O₃ solution (0.5 mL), then added to water / saturated brine, and extracted with ethyl acetate (3 × 5 mL). The combined organic phases were dried over anhydrous Na₂SO₄ and filtered. The solvent was removed by vacuum distillation, and the residue was purified by silica gel column chromatography (n-hexane / ethyl acetate) to give the corresponding amide 8 (12.5 mg, 59%). f = 0.3 (PE / EA = 5 : 1); White solid; 1 H NMR (400 MHz, Chloroform- d ) δ(ppm) 7.79 (d, J = 7.6 Hz, 2H), 7.53 – 7.25 (m, 8H), 6.84 (s, 1H), 4.60 (d, J =5.6 Hz, 2H); 13 C NMR (100 MHz, Chloroform- d ) δ (ppm) 167.4, 137.7, 134.3, 131.4, 128.6, 128.4, 127.7, 127.4, 126.9, 43.9.

[0046] The embodiments described above are merely preferred embodiments of the present invention, and not an exhaustive list of all possible implementations of the present invention. Any obvious modifications made by those skilled in the art without departing from the principles and spirit of the present invention should be considered to be included within the scope of protection of the claims of the present invention.

Claims

1. A method for synthesizing acylborane-based compounds, characterized by, The method comprises the following steps: The aldehyde shown in formula 1 or the alcohol shown in formula 1', the coordination borane compound shown in formula 2, the auxiliary agent and the solvent are sequentially added into a reactor, then the reactor is placed in an inert atmosphere and stirred at room temperature under blue light LED irradiation, after the reaction is completed, the acyl borane compound shown in formula 3 is obtained through purification treatment, and the reaction formula is as follows: ； Ar represents substituted or unsubstituted C 6-20 aryl, substituted or unsubstituted C 2-20 heteroaryl; wherein the substituents are selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 alkoxy, (C 1-6 alkyl)3Si-, C 6-20 aryl, C 2-6 alkynyl, C 1-6 alkyl-SO2-, (C 1-6 alkyl)2P(O)-, (C 1-6 alkoxy)2P(O)-, R1R2B-, -CN, C 1-6 haloalkyl, C 1-6 alkoxycarbonyl, C 3-8 cycloalkoxycarbonyl; the C 6-20 aryl, C 2-6 alkynyl optionally substituted with halogen, C 1-6 alkyl, C 1-6 alkoxy, (C 1-6 alkyl)3Si-; the R1, R2are selected from the group consisting of C 1-6 alkoxy, or R1, R2together with the B atom form an unsubstituted or C 1-6 alkyl-substituted five- to six-membered cyclic borate; R is selected from methyl or ethyl; preferably, R is methyl; The auxiliary agent is a persulfate or a silver salt; the solvent is acetonitrile, methanol or an acetonitrile / water mixed solvent.

2. The method of synthesis of claim 1, wherein, Ar represents substituted or unsubstituted phenyl, naphthyl; substituted or unsubstituted pyridyl, furanyl, thienyl; wherein the substituents are selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl, methoxy, trimethylsilyl, phenyl, ethynyl, methylsulfonyl, Me2P(O)-, (MeO)2P(O)-, (MeO)2B, (EtO)2B, , -CN, trifluoromethyl, methoxycarbonyl, cyclohexyloxycarbonyl, , the phenyl, ethynyl of the substituents are optionally substituted with fluorine, chlorine, bromine, methyl, ethyl, t-butyl, methoxy, trimethylsilyl.

3. The method of synthesis of claim 2, wherein, Ar represents substituted or unsubstituted phenyl; wherein the substituents are selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl, methoxy, trimethylsilyl, phenyl, trimethylsilyl ethynyl, methylsulfonyl, (MeO)2P(O)-, , -CN, trifluoromethyl, methoxycarbonyl, cyclohexyloxycarbonyl, , .

4. The method of synthesis according to any one of claims 1 to 3, wherein, The persulfate is selected from (NH4)2S2O8, Na2S2O8 and K2S2O8, preferably (NH4)2S2O8; the silver salt is selected from silver carbonate, silver bromide and silver nitrate, preferably silver bromide.

5. The method of synthesis according to any one of claims 1-3, wherein, The solvent is an acetonitrile / water mixed solvent.

6. The method of synthesis of claim 5, wherein, The volume ratio of acetonitrile to water in the acetonitrile / water mixed solvent is 1:3 to 3:1, preferably 1:

2.

7. The method of synthesis of claim 6, wherein, The amount of the solvent is such that the concentration of the compound shown in formula 1 or formula 1' is 0.01 to 1 mol / L, preferably 0.1 to 0.15 mol / L.

8. The method of synthesis according to any one of claims 1-3, wherein, The power of the blue light LED is 5 to 100 W, preferably 18 to 50 W.

9. The method of synthesis according to any one of claims 1-3, wherein, The molar ratio of the aldehyde shown in formula 1 or the alcohol shown in formula 1', the coordination borane compound shown in formula 2 and the auxiliary agent is 1:(1 to 5):(1 to 5), preferably 1:3:(3 to 4).

10. The method of synthesis according to any one of claims 1-3, wherein, The purification treatment is performed as follows: The reaction solution is quenched with NaHCO3, extracted, dried with anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the acyl borane compound shown in formula 3.

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