Method for preparing benzyl borate compound through chromium catalysis

Abstract

The invention discloses a method for preparing benzyl borate compounds through chromium catalysis, and belongs to the technical field of organic synthesis. According to the method, aryl carboxylic ester is taken as a raw material, pinacolborane is taken as a boron source and a hydrogen source, metal chromium salt is taken as a catalyst, a specific ligand and elemental magnesium are added, and reaction is performed in a tetrahydrofuran solvent, so that the deoxidation boronization reaction of the aryl carboxylic ester is realized. Benzyl monoborate or benzyl subunit diborate can be selectively prepared through ligand regulation and control. The method has the advantages of mild reaction conditions, cheap catalyst, wide raw material source, simple operation and good chemical selectivity.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic compound preparation, and particularly relates to a method for preparing benzyl borate compounds catalyzed by chromium. BACKGROUND

[0002] Organoboron compounds are of great value in chemical science, with benzyl boronates standing out as unique alkyl boron derivatives. Since the discovery of the Suzuki-Miyaura coupling reaction, the synthetic utility of organoboronates has been widely recognized, especially in cross-coupling, radical reactions, and the construction of C(sp 3 )-rich drugs, pesticides, and drug candidates.

[0003] Traditional methods for synthesizing organoboronates mainly include: (1) hydroboration: relying on the addition of borane to alkenes, but the substrate needs to be pre-contained with C=C bonds and it is difficult to control the regio- / stereo-selectivity; (2) transmetalation of organometallic compounds; (3) direct C-H bond borylation: requiring strong directing groups or highly active borylating reagents, and having limited functional group compatibility.

[0004] Carboxylic acids and carboxylic esters are common chemical raw materials, and have advantages such as reactivity, stability, wide source, and functional group compatibility. In HMPA, B2cat2 is used as a boron source, and a series of monoboronates and triboronate products can be prepared from corresponding carboxylic acids or carboxylate salts. The preparation of boronates from carboxylic esters can be achieved by decarbonyl borylation, but direct deoxyborylation of ester groups is rarely explored. Direct deoxyborylation of carboxylic esters can avoid the pre-functionalization step, and has a unique step advantage in deoxyborylation reactions, becoming an ideal precursor for the synthesis of monoboron / multiboron compounds. The currently reported deoxyborylation reaction of carboxylic esters uses alkyl carboxylic esters as raw materials, pinacol bisboronic ester as a boron source, and iron salt as a catalyst, with ethanol as a proton source, to undergo 1,1-diborylation to obtain geminal diboronate products. This method can only be applied to alkyl carboxylic esters and cannot be compatible with aryl carboxylic esters, and can only generate 1,1-bisboronate products with low yield.

[0005] In summary, although the method for deoxyborylation of carboxylic esters to generate monoboronate or multiboronate compounds has been reported, the substrate range is limited to alkyl carboxylic esters, which is not suitable for aryl carboxylic esters, and pinacol bisboronic ester is used as a boron source, which has the disadvantages of low boron utilization, low yield, and poor substrate compatibility. It is extremely important to develop a method for deoxyborylation of aryl carboxylic esters as raw materials, pinacol borane as hydrogen source and boron source, transition metal catalysis, efficient, high selectivity, mild conditions, to generate monoboronate or bisboronate compounds. SUMMARY

[0006] To achieve the above technical purpose, reach the above technical effect, the present application provides the following technical scheme:

[0007] A method for preparing benzyl borate compound catalyzed by chromium, the method comprises: in the presence of chromium catalyst, ligand and magnesium element, aryl carboxylate and pinacol borane are subjected to deoxyboronation reaction in tetrahydrofuran solvent under inert atmosphere, to generate benzyl monoboronic acid ester or benzylidene diboronic acid ester;

[0008] Among them, the structure general formula of aryl carboxylate, benzyl monoboronic acid ester and benzylidene diboronic acid ester is as follows:

[0009] 、 、

[0010] Among them, Ar is selected from the following groups: 4-methoxyphenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-phenylphenyl, 4-((4-n-propyl)cyclohexyl)phenyl, 4-((4-trimethylsilyl)phenyl)phenyl, 4-((dimethyl tert-butyl silyl)oxy)phenyl, 4-phenoxyphenyl, 4-hydroxyphenyl, 4-pinacol boron phenyl, 2-methylphenyl, 2,5-dimethylphenyl, 2-methyl-3-methoxyphenyl, 2-ethoxyphenyl, 2-benzylphenyl, 2-(4-methylphenyl)phenyl, 2-naphthyl, 1-naphthyl, 6-benzofuranyl, 4-benz(1,4)cyclohexenylphenyl, 4-(3-furyl)phenyl, 4-(3-thiophenyl)phenyl, phenyl, 4-((4-trifluoromethoxy)phenyl)phenyl, 4-(2-methoxyphenyl)phenyl, 4-chlorophenyl, 3-furyl, 3-thiophenyl;

[0011] Among them, R is selected from: methyl, ethyl, tert-butyl, phenyl.

[0012] Preferably, the chromium catalyst is selected from at least one of: dichloride chromium, trichloride chromium, chromium acetylacetone.

[0013] Preferably, the ligand is selected from at least one of the following: 4,4'-di-tert-butyl-6,6'-dimethylbipyridine, 4,4'-dimethylbipyridine, 5,5'-dimethylbipyridine, 6,6'-dimethylbipyridine, 2,2':6',2''-terpyridine, 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine, 2,2'-biquinoline.

[0014] Preferably, when the method is used for preparing benzyl monoboronic acid ester, the ligand is preferably 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine.

[0015] Preferably, when the method is used to prepare benzylidene bisboronic acid ester, the ligand is preferably 4,4'-di-tert-butyl-6,6'-dimethylbipyridine, and lithium chloride is simultaneously added as an additive.

[0016] Preferably, the chromium catalyst and the ligand are added in an amount of 5-20% of the molar amount of the aryl carboxylate.

[0017] Preferably, the magnesium element is added in an amount of 1-5 times of the molar amount of the aryl carboxylate.

[0018] Preferably, the reaction temperature of the deoxygenation boronation reaction is 40-100℃, preferably 80℃ when preparing the benzyl monoboronic acid ester, and preferably 40℃ when preparing the benzylidene bisboronic acid ester.

[0019] Compared with the prior art, the present application has the following beneficial effects:

[0020] The method of the present application has the characteristics of mild reaction conditions, inexpensive catalyst, widely available raw materials, simple operation, and good chemical selectivity. DETAILED DESCRIPTION

[0021] The technical solutions in the embodiments of the present application will be described below in conjunction with the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0022] The present application uses metal chromium salt as a catalyst, pinacol borane as a boron source and hydrogen source, and controls the deoxygenation boronation reaction with aryl carboxylate through a ligand, to provide a preparation method for benzyl monoboronic acid ester and benzylidene bisboronic acid ester compounds with mild reaction conditions, inexpensive catalyst, widely available raw materials, simple operation, and good chemical selectivity.

[0023] The reaction general formula provided by the present application is shown in the following formula:

[0024]

[0025] Ar is selected from: 4-methoxyphenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-phenylphenyl, 4-(4-n-propyl)cyclohexyl)phenyl, 4-((4-trimethylsilyl)phenyl)phenyl, 4-((dimethyltert-butylsilyl)oxy)phenyl, 4-phenoxyphenyl, 4-hydroxyphenyl, 4-pinacolborylphenyl, 2-methylphenyl, 2,5-dimethylphenyl, 2-methyl-3-methoxyphenyl, 2-ethoxyphenyl, 2-benzylphenyl, 2-(4-methylphenyl)phenyl, 2-naphthyl, 1-naphthyl, 6-benzofuranyl, 4-benzo(1,4)epoxyhexacyclophenyl, 4-(3-furanyl)phenyl, 4-(3-thienyl)phenyl, phenyl, 4-((4-trifluoromethoxy)phenyl)phenyl, 4-(2-methoxyphenyl)phenyl, 4-chlorophenyl, 3-furanyl, 3-thienyl;

[0026] Wherein, R is selected from: methyl, ethyl, tert-butyl, phenyl;

[0027] The catalyst chromium salt is selected from: chromium dichloride, chromium trichloride, and chromium acetylacetone;

[0028] The ligands are selected from: 4,4'-di-tert-butylbipyridine, 4,4'-di-tert-butyl-6,6'-dimethylbipyridine, 4,4'-dimethylbipyridine, 5,5'-dimethylbipyridine, 6,6'-dimethylbipyridine, 2,2':6',2'' terpyridine, 4,4',4''-tri-tert-butyl-2,2':6',2'' terpyridine, and 2,2'-biquinoline; the ligand structures are shown below:

[0029]

[0030] When preparing benzyl monoboronic esters, 4,4',4''-tritert-butyl-2,2':6',2''-terpyridine is preferred as the ligand, and when preparing benzyl diboronic esters, 4,4'-ditert-butyl-6,6'-dimethylbipyridine is preferred as the ligand, and lithium chloride is added as an additive.

[0031] The amount of the catalyst and ligand added is 5-20% of the molar amount of the aryl carboxylic acid ester.

[0032] The amount of magnesium added is 1-5 times the molar amount of aryl carboxylic acid ester.

[0033] In the above methods, the reaction temperature is 40–100℃, preferably 80℃ for preparing benzyl monoboronate and preferably 40℃ for preparing benzyl diboronate.

[0034] In the above method, the reaction time is 3-12 hours.

[0035] The general steps for preparing benzyl borate esters from aryl carboxylic acid esters are as follows:

[0036] The aryl carboxylate 1, pinacolborane, chromium dichloride, ligand and elemental magnesium were placed in a reaction tube under a nitrogen atmosphere, tetrahydrofuran was added as a solvent, and the reaction was carried out in an oil bath pot. After the reaction was completed, the mixture was quenched with a saturated ammonium chloride solution, extracted with dichloromethane, and the extract was subjected to removal of the volatile solvent under reduced pressure, and the desired target product was purified by silica gel column chromatography.

[0037] The general procedure for preparing benzylidene bisboronate from aryl carboxylate is as follows:

[0038] The aryl carboxylate 1, pinacolborane, chromium dichloride, ligand, elemental magnesium, and additive lithium chloride were placed in a reaction tube under a nitrogen atmosphere, tetrahydrofuran was added as a solvent, and the reaction was carried out in an oil bath pot. After the reaction was completed, the mixture was quenched with a saturated ammonium chloride solution, extracted with dichloromethane, and the extract was subjected to removal of the volatile solvent under reduced pressure, and the desired target product was purified by silica gel column chromatography.

[0039] The following examples are intended to further illustrate the present application without limiting the same. The structures of the reactants used in the examples are as follows:

[0040]

[0041] Example 1

[0042] Methyl 4-methoxybenzoate 1a (33 mg, 0.2 mmol), catalyst chromium dichloride (2.5 mg, 0.02 mmol), ligand 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine (8 mg, 0.02 mmol), elemental magnesium (19 mg, 0.8 mmol), pinacolborane (145 μL, 1.0 mmol), and tetrahydrofuran (1 mL) were placed in a 25 mL reaction tube under a nitrogen atmosphere, and the reaction was carried out in an 80°C oil bath pot for 12 hours. After the reaction was completed, the mixture was quenched with a saturated ammonium chloride solution, extracted with dichloromethane, and the extract was subjected to removal of the volatile solvent under reduced pressure, and the desired target product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain benzyl borate 2a as a colorless oil in a yield of 40 mg, 80%. At this time, the corresponding benzylidene bisboronate 3a product was obtained in a yield of 9 mg, 13%.

[0043]

[0044] 2a: 1 H NMR (400 MHz, CDC13): δ = 7.13-7.07 (m, 2H), 6.83-6.77 (m, 2H), 3.77 (s, 3H), 2.23 (s, 2H), 1.24 (s, 12H); 13C NMR (100 MHz, CDCI3): δ = 157.2, 130.6, 129.9, 113.9, 83.5, 55.3, 24.9; 11 B NMR (128 MHz, CDCI3): δ = 33.10.

[0045] Example 2

[0046] In this example, 1b was used instead of 1a in Example 1 with equimolar amount, and the eluent was petroleum ether / ethyl acetate (40:1 by volume), and other procedures were the same as Example 1. The mono-boronate 2b was obtained as colorless oil in 38 mg yield of 81%. The corresponding di-boronate product was obtained in 4 mg yield of 5%.

[0047]

[0048] 2b: 1 H NMR (400 MHz, CDCI3): δ = 7.10-7.02 (m, 4H), 2.30 (s, 3H), 2.25 (s, 1H), 1.23 (s, 12H); 13 C NMR (100 MHz, CDCI3): δ = 135.5, 134.3, 129.1, 129.0, 83.5, 24.9, 21.1; 11 B NMR (128 MHz, CDCI3): δ = 32.92.

[0049] Example 3

[0050] In this example, 1c was used instead of 1a in Example 1 with equimolar amount, and the eluent was petroleum ether / ethyl acetate (40:1 by volume), and other procedures were the same as Example 1. The mono-boronate 2c was obtained as colorless oil in 41 mg yield of 75%. The corresponding di-boronate product was obtained in 6 mg yield of 8%.

[0051]

[0052] 2c: 1 H NMR (400 MHz, CDCI3): δ = 7.28-7.24 (m, 2H), 7.14-7.10 (m, 2H), 2.27 (s, 2H), 1.30 (s, 9H), 1.25 (s, 12H); 13 C NMR (100 MHz, CDCI3): δ = 147.6, 135.5, 128.8, 125.3, 83.5, 34.4, 31.6, 24.9; 11B NMR (128 MHz, CDC13): δ = 33.20

[0053] Example 4

[0054] In this example, 1d was used instead of 1a in Example 1 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (40:1 by volume), and other steps were the same as Example 1, to give mono-boronate 2d as colorless oil in 42 mg in 71% yield. The corresponding di-boronate product was 6 mg in 7% yield at this time.

[0055]

[0056] 2d: 1 H NMR (400 MHz, CDC13): δ = 7.60-7.57 (m, 2H), 7.51-7.47 (m, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.34-7.25 (m, 3H), 2.35 (s, 2H), 1.26 (s, 12H); 13 C NMR (100 MHz, CDC13): δ = 141.4, 138.0, 137.9, 129.5, 128.8, 127.2, 127.1, 127.0, 83.6, 24.9; 11 B NMR (128 MHz, CDC13): δ = 33.31.

[0057] Example 5

[0058] In this example, 1e was used instead of 1a in Example 1 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (40:1 by volume), and other steps were the same as Example 1, to give mono-boronate 2e as white solid in 41 mg in 60% yield. The corresponding di-boronate product was 10 mg in 11% yield at this time.

[0059]

[0060] 2e: 1 H NMR (400 MHz, CDC13): δ = 7.12-7.05 (m, 4H), 2.41 (tt, J = 12.2, 3.2 Hz, 1H), 2.26 (s, 2H), 1.91-1.80 (m, 4H), 1.46-1.27 (m, 7H), 1.24 (s, 12H), 1.08-0.98 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDC13): δ = 144.4, 135.9, 129.0, 126.9, 83.5, 44.3, 39.9, 37.2, 34.5, 33.8, 24.9, 20.2, 14.6; 11 B NMR (128 MHz, CDC13): δ = 33.40. HRMS (ESI + ) calcd for C 22 H 35 BO2 + [M+H] + 343.2803, found 343.2801

[0061] Example 6

[0062] In this example, 1f was used to replace 1a in Example 1 with equimolar amount, and the eluent was petroleum ether / ethyl acetate (40:1 by volume), and other steps were the same as Example 1, to obtain monoboronate 2f as a white solid, with a yield of 54 mg and a yield of 74%. At this time, the yield of the corresponding diboronate product was 11 mg and the yield was 11%.

[0063]

[0064] 2f: 1 H NMR (400 MHz, CDC13): δ = 7.58 (s, 4H), 7.49 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 8.1 Hz, 2H), 2.34 (s, 2H), 1.26 (s, 12H), 0.30 (s, 9H); 13 CNMR (100 MHz, CDC13): δ = 141.8, 138.8, 138.1, 137.8, 133.9, 129.6, 127.2, 126.4, 83.6, 29.6, 24.9, -0.9; 11 B NMR (128 MHz, CDC13): δ = 33.40. HRMS (ESI + ) calcd for C 22 H 31 BO2Si + [M+H] + 367.2259, found 367.2257. 2f’: 1H NMR (400 MHz, CDC13): δ = 7.58 (d, J = 1.8 Hz, 4H), 7.51 - 7.45 (m, 2H), 7.34 (d, J = 8.1 Hz, 2H), 2.36 (s, 1H), 1.26 (s, 12H), 1.24 (s, 12H), 0.30 (s, 9H); 13 C NMR (100 MHz, CDC13): δ = 142.0, 139.0, 138.4, 137.0, 133.8, 129.7, 126.9, 126.3, 83.6, 24.83, 24.77, -0.9; 11 B NMR (128 MHz, CDC13): δ = 33.32

[0065] Example 7

[0066] In this example, 1 g of 1a in Example 1 was replaced with equimolar 1g, and the eluent was petroleum ether / ethyl acetate (volume ratio 40:1), and other steps were the same as Example 1, to obtain colorless oily monoborate ester 2g, yield 48 mg, yield 69%. At this time, the yield of the corresponding diborate product is 8 mg, and the yield is 9%.

[0067]

[0068] 2g: 1 H NMR (400 MHz, CDC13): δ = 7.05-7.01 (m, 2H), 6.73-6.69 (m, 2H), 2.21 (s, 2H), 1.23 (s, 12H), 0.97 (s, 9H), 0.17 (s, 6H); 13 C NMR (100 MHz, CDC13): δ = 153.1, 131.2, 129.9, 120.0, 83.5, 25.9, 24.8, 18.3, -4.3; 11 B NMR (128 MHz, CDC13): δ = 33.50

[0069] Example 8

[0070] In this example, 1a in Example 1 was replaced with equimolar 1h, and other steps were the same as Example 1, to obtain white solid monoborate ester 2h, yield 45 mg, yield 72%. At this time, the yield of the corresponding diborate product is 13 mg, and the yield is 15%.

[0071]

[0072] 2h: 1 H NMR (400 MHz, CDCl3): δ = 7.33–7.28 (m, 2H), 7.17–7.12 (m, 2H),7.06 (t, J = 7.4 Hz, 1H), 7.01–6.97 (m, 2H), 6.93–6.88 (m, 2H), 2.28 (s, 2H),1.25 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 158.0, 154.5, 133.7, 130.3,129.7, 122.9, 119.2, 118.5, 83.6, 24.9; 11 B NMR (128 MHz, CDCl3): δ = 33.43.HRMS (ESI + ) calcd for C 19 H 23 BO3 + [M+H] + 311.1813, found 311.1815

[0073] Example 9

[0074] In this example, equimolar of 1i instead of 1a in Example 1, eluent is petroleum ether / ethyl acetate (volume ratio of 5:1), other steps are the same as Example 1, to obtain white solid monoboronic acid ester 2i, yield of 35 mg, yield of 74%. At this time, the corresponding bis-boronic acid ester product yield is 11 mg, yield of 15%.

[0075]

[0076] 2i: 1 H NMR (400 MHz, CDCl3): δ = 7.05–7.00 (m, 2H), 6.71–6.65 (m,2H), 4.80 (s, 1H), 2.21 (s, 2H), 1.24 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ =153.1, 130.6, 130.1, 115.3, 83.6, 24.9; 11 B NMR (128 MHz, CDCl3): δ = 33.19。

[0077] Example 10

[0078] In this example, 1j was used to replace 1a in Example 1 in equimolar amount, and other steps were the same as Example 1, to obtain monoboronate 2j in white solid, with a yield of 55 mg and a yield of 80%. At this time, the yield of the corresponding diboronate product was 11 mg and the yield was 12%.

[0079]

[0080] 2j: 1 H NMR (400 MHz, CDCl3): δ = 7.70–7.66 (m, 2H), 7.20–7.16 (m, 2H),2.30 (s, 2H), 1.33 (s, 12H), 1.21 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ =142.5, 135.0, 128.6, 83.7, 83.6, 25.0, 24.8; 11 B NMR (128 MHz, CDCl3): δ =32.85, 30.24。

[0081] Example 11

[0082] In this example, 1k was used to replace 1a in Example 1 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (volume ratio 40:1), and other steps were the same as Example 1, to obtain monoboronate 2k in colorless oil, with a yield of 35 mg and a yield of 76%. At this time, the yield of the corresponding diboronate product was 7 mg and the yield was 10%.

[0083]

[0084] 2k: 1 H NMR (400 MHz, CDCl3): δ = 7.16–7.02 (m, 4H), 2.28 (s, 3H), 2.27(s, 2H), 1.23 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 137.7, 136.1, 129.9,129.6, 126.0, 125.3, 83.5, 24.9, 20.2; 11 B NMR (128 MHz, CDCl3): δ = 33.38

[0085] Example 12

[0086] In this example, 1l was used instead of 1a in Example 1, and the eluent was petroleum ether / ethyl acetate (volume ratio 40:1), and other steps were the same as Example 1, to obtain monoboronate 2l as colorless oil, yield 36 mg, yield 74%. At this time, the yield of the corresponding diboronate product was 8 mg, and the yield was 11%.

[0087]

[0088] 2l: 1 H NMR (400 MHz, CDCl3): δ = 7.02–6.94 (m, 2H), 6.86 (d, J = 7.6Hz, 1H), 2.28 (s, 3H), 2.23 (s, 5H), 1.24 (s, 12H); 13 C NMR (100 MHz, CDCl3):δ = 137.4, 135.2, 132.9, 130.5 129.8, 126.0, 83.5, 24.9, 21.1, 19.7; 11 B NMR(128 MHz, CDCl3): δ = 33.11. HRMS (ESI + ) calcd for C15H 23 BO2 + [M+H] + 247.1864,found 247.1860. 2l’: 1 H NMR (400 MHz, CDCl3): δ = 7.23 (s, 1H), 6.97 (d, J =7.6 Hz, 1H), 6.81 (d, J = 7.3 Hz, 1H), 2.34 (s, 1H), 2.28 (s, 3H), 2.20 (s,3H), 1.24 (s, 12H), 1.23 (s, 12H). 13 C NMR (100 MHz, CDCl3): δ = 138.0, 134.9,132.9, 130.0, 129.7, 125.4, 83.4, 29.9, 24.9, 24.7。 11 B NMR (128 MHz, CDCl3):δ = 33.43

[0089] Example 13

[0090] In this example, equimolar of 1m was used to replace 1a in Example 1, and other steps were the same as Example 1, to obtain monoboronate 2m as colorless oil, with a yield of 40 mg and a yield of 76%. At this time, the yield of the corresponding diboronate product was 8 mg and the yield was 11%.

[0091]

[0092] 2m: 1 H NMR (400 MHz, CDCl3): δ = 7.05 (t, J = 7.9 Hz, 1H), 6.78 (d, J = 7.6 Hz, 1H), 6.67 (d, J = 8.2 Hz, 1H), 3.81 (s, 3H), 2.28 (s, 2H), 2.15 (s,3H), 1.23 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 157.7, 139.1, 125.9, 124.6,122.3, 107.4, 83.5, 55.6, 24.9, 12.1; 11 B NMR (128 MHz, CDCl3): δ = 33.41.HRMS (ESI + ) calcd for C 15 H 23 BO3 + [M+H] + 263.1813, found 263.1818

[0093] Example 14

[0094] In this example, equimolar of 1n was used to replace 1a in Example 1, and other steps were the same as Example 1, to obtain monoboronate 2n as colorless oil, with a yield of 41 mg and a yield of 78%. At this time, the yield of the corresponding diboronate product was 5 mg, and the yield was 7%.

[0095]

[0096] 2n: 1 H NMR (400 MHz, CDCl3): δ = 7.17–7.05 (m, 2H), 6.87–6.75 (m, 2H),4.03 (q, J = 7.0 Hz, 2H), 2.21 (s, 2H), 1.42 (t, J = 7.0 Hz, 3H), 1.24 (s,12H); 13C NMR (100 MHz, CDCl3): δ = 156.7, 130.5, 128.3, 126.3, 120.4, 111.0, 83.2, 63.4, 24.9, 15.1; 11 B NMR (128 MHz, CDCl3): δ= 33.76. HRMS (ESI + )calcd forC 15 H 23 BO3 + [M+H] + 263.1813, found 263.1816. 2n’: 1 H NMR (400 MHz, CDCl3):δ=7.09–7.02(m,1H),6.92(d,J= 8.6 Hz, 1H), 6.85(t,J=7.2Hz,1H),6.76(d,J=8.1Hz,1H),3.97(q,J = 6.9 Hz, 2H), 2.58 (s, 1H), 1.35 (t, J = 4.1 Hz, 3H), 1.24 (d, J = 1.7Hz, 12H), 1.22 (s, 12H). 13 C NMR (100 MHz, CDCl3): δ = 151.8, 130.0, 125.5, 120.4, 114.0, 111.2, 83.2, 63.8, 25.0, 24.7, 15.1. 11 B NMR (128 MHz, CDCl3): δ= 33.06

[0097] Example 15

[0098] In this example, equimolar of 1o was used to replace 1a in Example 1, and the eluent was petroleum ether / ethyl acetate (volume ratio 40:1), and other steps were the same as Example 1, to obtain a single borate 2o in white solid, the yield was 47 mg, the yield was 77%. At this time, the corresponding double borate product yield was 7 mg, the yield was 8%.

[0099]

[0100] 2o: 1H NMR (400 MHz, CDC13): δ 7.30-7.24 (m, 2H), 7.22-7.12 (m, 5H), 7.09 (td, J = 7.3, 1.7 Hz, 1H), 7.02 (d, J = 7.4 Hz, 1H), 4.01 (s, 2H), 2.26 (s, 2H), 1.21 (s, 12H); 13 C NMR (100 MHz, CDC13): δ = 140.8, 138.6, 137.7, 130.2, 130.1, 129.1, 128.5, 126.5, 126.0, 125.4, 83.5, 39.5, 24.9; 11 B NMR (128 MHz, CDC13): δ = 33.12. HRMS (ESI + ) calcd for C 20 H 25 BO2 + [M+H] + 309.2020, found 309.2025

[0101] Example 16

[0102] In this example, 1p was used to replace 1a in Example 1, and the eluent was petroleum ether / ethyl acetate (volume ratio 40:1), and other steps were the same as Example 1, to obtain a single borate ester 2p in the form of a white solid, with a yield of 41 mg and a yield of 67%. At this time, the yield of the corresponding double borate ester product was 9 mg and the yield was 10%.

[0103]

[0104] 2p: 1 H NMR (400 MHz, CDC13): δ 7.30-7.24 (m, 2H), 7.22-7.12 (m, 5H), 7.09 (td, J = 7.3, 1.7 Hz, 1H), 7.02 (d, J = 7.4 Hz, 1H), 4.01 (s, 2H), 2.26 (s, 2H), 1.21 (s, 12H); 13 C NMR (100 MHz, CDC13): δ = 140.8, 138.6, 137.7, 130.2, 130.1, 129.1, 128.5, 126.5, 126.0, 125.4, 83.5, 39.5, 24.9; 11 B NMR (128 MHz, CDC13): δ = 33.12. HRMS (ESI

[0105] Example 17

[0106] In this example, 1q was used to replace 1a in Example 1 with equimolar amount, and the eluent was petroleum ether / ethyl acetate (40:1 by volume), and other steps were the same as Example 1, to obtain monoboronate 2q in white solid, with a yield of 37 mg and a yield of 69%. At this time, the yield of the corresponding diboronate product was 10 mg, and the yield was 13%.

[0107]

[0108] 2q: 1 H NMR (400 MHz, CDCl3): δ = 7.81–7.71 (m, 3H), 7.62 (p, J = 0.9Hz, 1H), 7.45–7.31 (m, 3H), 2.46 (s, 2H), 1.24 (s, 12H); 13 C NMR (100 MHz,CDCl3): δ = 136.5, 133.9, 131.6, 128.4, 127.8, 127.7, 127.4, 126.7, 125.8,124.8, 83.6, 24.9; 11 B NMR (128 MHz, CDCl3): δ = 33.46

[0109] Example 18

[0110] In this example, 1r was used to replace 1a in Example 1 with equimolar amount, and the eluent was petroleum ether / ethyl acetate (40:1 by volume), and other steps were the same as Example 1, to obtain monoboronate 2r in colorless oil, with a yield of 43 mg and a yield of 80%. At this time, the yield of the corresponding diboronate product was 4 mg, and the yield was 5%.

[0111]

[0112] 2r: 1 H NMR (400 MHz, CDCl3): δ = 8.05–8.00 (m, 1H), 7.86–7.82 (m, 1H),7.68 (dd, J = 7.5, 1.6 Hz, 1H), 7.53–7.44 (m, 2H), 7.41–7.34 (m, 2H), 2.71(s, 2H), 1.21 (s, 12H); 13C NMR (100 MHz, CDCl3): δ = 135.7, 133.9, 132.6,128.6, 126.6, 125.9, 125.5, 125.5, 124.6, 83.7, 24.8; 11 B NMR (128 MHz,CDCl3): δ = 33.54.

[0113] Example 19

[0114] In this example, 1s was used to replace 1a in Example 1 with equimolar amount, and the eluent was petroleum ether / ethyl acetate (volume ratio 40:1), and other steps were the same as Example 1, to obtain a white solid monoboronate 2s, yield 37 mg, yield 71%. At this time, the corresponding bisboronate product yield was 15 mg, yield 11%.

[0115]

[0116] 2s: 1 H NMR (400 MHz, CDCl3): δ = 7.53 (d, J = 2.2 Hz, 1H), 7.45 (d, J= 8.0 Hz, 1H), 7.35 (dt, J = 1.6, 0.8 Hz, 1H), 7.07 (dd, J = 7.9, 1.4 Hz,1H), 6.70 (dd, J = 2.2, 0.9 Hz, 1H), 2.41 (s, 2H), 1.24 (s, 12H); 13 C NMR (100MHz, CDCl3): δ = 155.6, 144.2, 135.4, 124.6, 124.4, 120.7, 111.7, 106.5,83.6, 24.9; 11 B NMR (128 MHz, CDCl3): δ = 33.16. HRMS (ESI + ) calcd for C 15 H 19 BO3 + [M+H] + 259.1500, found 259.1501.

[0117] Example 20

[0118] In this example, 1t was used to replace 1a in Example 1, and other steps were the same as Example 1, to obtain monoboronic ester 2t as a white solid, with a yield of 48 mg and a yield of 68%. At this time, the yield of the corresponding diboronic ester product was 6 mg and the yield was 6%.

[0119]

[0120] 2t: 1 H NMR (400 MHz, CDCl3): δ = 7.41 (d, J = 7.9 Hz, 2H), 7.22 (d, J= 8.0 Hz, 2H), 7.12–7.04 (m, 2H), 6.93–6.87 (m, 1H), 4.28 (s, 4H), 2.32 (s,2H), 1.25 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 143.7, 142.9, 137.5, 137.3,135.1, 129.5, 126.8, 120.1, 117.6, 115.7, 83.6, 64.6, 24.9; 11 B NMR (128 MHz,CDCl3): δ = 33.05. HRMS (ESI + ) calcd for C 21 H 25 BO4 + [M+H] + 353.1919, found353.1923。

[0121] Example 21

[0122] In this example, 1u was used to replace 1a in Example 1, and the eluent was petroleum ether / ethyl acetate (volume ratio 40:1), and other steps were the same as Example 1, to obtain monoboronic ester 2u as a white solid, with a yield of 40 mg and a yield of 70%. At this time, the yield of the corresponding diboronic ester product was 8 mg and the yield was 10%.

[0123]

[0124] 2u: 1H NMR (400 MHz, CDC13): δ = 7.76-7.63 (m, 1H), 7.45 (t, J = 1.7 Hz, 1H), 7.38-7.34 (m, 2H), 7.22-7.18 (m, 2H), 6.68 (dd, J = 1.8, 0.9 Hz, 1H), 2.30 (s, 2H), 1.24 (s, 12H); 13 C NMR (100 MHz, CDC13): δ = 143.6, 138.2, 137.7, 129.5, 129.1, 126.6, 126.0, 109.0, 83.6, 24.9; 11 B NMR (128 MHz, CDC13): δ = 33.0. HRMS (ESI + ) calcd for C 17 H 21 BO3 + [M+H] + 285.1657, found 285.1653.

[0125] Example 22

[0126] In this example, 1v was used to replace 1a in Example 1 with equimolar amount, and the eluent was petroleum ether / ethyl acetate (volume ratio of 40:1), and other steps were the same as Example 1, to obtain monoboronate 2v as a white solid, with a yield of 45 mg and a yield of 75%. At this time, the yield of the corresponding diboronate product was 9 mg and the yield was 10%.

[0127]

[0128] 2v: 1 H NMR (400 MHz, CDC13): δ = 7.76-7.63 (m, 1H), 7.45 (t, J = 1.7 Hz, 1H), 7.38-7.34 (m, 2H), 7.22-7.18 (m, 2H), 6.68 (dd, J = 1.8, 0.9 Hz, 1H), 2.30 (s, 2H), 1.24 (s, 12H); 13C NMR (100 MHz, CDCl3): δ = 141.4, 140.9, 139.1, 136.3, 133.82, 133.77, 128.5, 126.8, 126.4, 122.0, 25.3, 15.0, -1.0. HRMS (ESI + ): calcd for C 19 H 25 Si [M+H] + 281.1720, found 281.1725

[0129] Example 23

[0130] Methyl 4-methoxybenzoate la (33 mg, 0.2 mmol), catalyst chromium dichloride (2.5 mg, 0.02 mmol), ligand 4,4'-di-tert-butyl-6,6'-dimethylbipyridine (6 mg, 0.02 mmol), elemental magnesium (14 mg, 0.8 mmol), pinacolborane (116 μL, 0.8 mmol), lithium chloride (8 mg, 0.2 mmol) and tetrahydrofuran (1 mL) were placed in a 25 mL reaction tube and reacted in a 40 °C oil bath for 3 hours under nitrogen atmosphere. After the reaction was completed, the mixture was quenched with water and extracted with dichloromethane. The extract was subjected to removal of volatile solvents under reduced pressure and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain a diboronate 3a as a white solid in a yield of 59 mg at a yield of 79%. At this time, the corresponding monoboronate product was obtained in a yield of 4 mg at a yield of 9%.

[0131]

[0132] 3a: 1 H NMR (400 MHz, CDCl3): δ = 7.20–7.15 (m, 2H), 6.79–6.74 (m, 2H),3.76 (s, 3H), 2.23 (s, 1H), 1.22 (s, 12H), 1.21 (s, 12H); 13 C NMR (100 MHz,CDCl3): δ = 156.7, 131.4, 123.0, 113.6, 83.4, 55.2, 24.8, 24.7; 11 B NMR (128MHz, CDCl3): δ = 33.39

[0133] Example 24

[0134] In this example, 1b was used instead of 1a in Example 23 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to give the bisboronate 3b as a white solid, with a yield of 52 mg and a yield of 72%. The corresponding monoboronate product was 6 mg in yield of 13% at this time.

[0135]

[0136] 3b: 1 H NMR (400 MHz, CDCl3): δ = 7.18–7.12 (m, 2H), 7.02 (d, J = 7.9Hz, 2H), 2.28 (s, 3H), 2.25 (s, 1H), 1.22 (s, 12H), 1.21 (s, 12H); 13 C NMR(100 MHz, CDCl3): δ = 136.3, 133.5, 129.1, 128.8, 83.5, 24.82, 24.75, 21.1; 11 B NMR (128 MHz, CDCl3): δ = 32.75。

[0137] Example 25

[0138] In this example, 1c was used instead of 1a in Example 23 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to give the bisboronate 3c as a white solid, with a yield of 60 mg and a yield of 75%. The corresponding monoboronate product was 8 mg in yield of 15% at this time.

[0139]

[0140] 3c: 1 H NMR (400 MHz, CDCl3): δ = 7.23–7.17 (m, 4H), 2.29 (s, 1H), 1.29(s, 9H), 1.24 (s, 12H), 1.23 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 146.7,136.2,128.9, 125.0, 83.4, 34.3, 31.6, 24.82, 24.79; 11 B NMR (128 MHz, CDCl3):δ = 32.78

[0141] Example 26

[0142] In this example, 1d was used to replace 1a in Example 23 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to obtain bisboronate 3d as a white solid, with a yield of 62 mg and a yield of 74%. At this time, the corresponding monoboronate product was 7 mg in yield and 12% in yield.

[0143]

[0144] 3d: 1 H NMR (400 MHz, CDCl3): δ = 7.61–7.56 (m, 2H), 7.50–7.44 (m, 2H),7.40 (t, J = 7.7 Hz, 2H), 7.37–7.26 (m, 3H), 2.36 (s, 1H), 1.25 (s, 12H),1.24 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 141.6, 138.9, 137.0, 129.7,128.7, 127.0, 126.8, 126.7, 83.6, 24.83, 24.76; 11 B NMR (128 MHz, CDCl3): δ =33.28

[0145] Example 27

[0146] In this example, 1e was used to replace 1a in Example 23 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 2, to obtain bisboronate 3e as a white solid, with a yield of 74 mg and a yield of 79%. At this time, the corresponding monoboronate product was 7 mg in yield and 11% in yield.

[0147]

[0148] 3e: 1H NMR (400 MHz, CDC13): δ = 7.18-7.15 (m, 2H), 7.07-7.02 (m, 2H), 2.44-2.34 (m, 1H), 2.28 (s, 1H), 1.89-1.81 (m, 4H), 1.47-1.33 (m, 5H), 1.23 (s, 12H), 1.22 (s, 12H), 1.07-1.00 (m, 2H), 0.95-0.82 (m, 5H); 13 C NMR (100 MHz, CDC13): δ = 143.5, 136.6, 129.1, 126.6, 83.4, 44.2, 40.0, 37.2, 34.5, 33.9, 24.82, 24.78, 20.2, 14.6; 11 B NMR (128 MHz, CDC13): δ = 33.79. HRMS (ESI + ): calcd for C 28 H 46 B2O4 + [M+H] + 469.3655, found 469.3651

[0149] Example 28

[0150] In this example, 1 g of 1a was replaced with equimolar amount of 1b, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as in Example 23 to give the bisboronate ester 3g as a white solid with a yield of 65 mg (69%). The corresponding monoboronate ester product was produced in this time with a yield of 12 mg (8%).

[0151]

[0152] 3g: 1 H NMR (400 MHz, CDC13): δ = 7.15-7.07 (m, 2H), 6.74-6.64 (m, 2H), 2.23 (s, 1H), 1.22 (s, 12H), 1.21 (s, 12H), 0.96 (s, 9H), 0.17 (s, 6H); 13 CNMR (100 MHz, CDC13): δ = 152.6, 131.9, 130.0, 119.7, 83.4, 25.9, 24.8, 24.7, 18.3, -4.3;11 B NMR (128 MHz, CDCl3): δ = 33.64

[0153] Example 29

[0154] In this example, 1h was used to replace 1a in Example 23 in equimolar amount, and other steps were the same as Example 23, to give bisboronate 3h as a white solid, with a yield of 66 mg, 76% yield. The corresponding monoboronate product was 4 mg, 7% yield.

[0155]

[0156] 3h: 1 H NMR (400 MHz, CDCl3): δ = 7.32–7.21 (m, 4H), 7.08–6.97 (m, 3H),6.91–6.86 (m, 2H), 2.30 (s, 1H), 1.24 (s, 12H), 1.23 (s, 12H); 13 C NMR (100MHz, CDCl3): δ = 158.1, 153.9, 134.6, 130.4, 129.6, 122.7, 119.0, 118.5,83.5, 24.8, 24.7; 11 B NMR (128 MHz, CDCl3): δ = 33.45. HRMS (ESI + ): calcd forC 25 H 34 B2O5 + [M+H] + 437.2665, found 437.2662

[0157] Example 30

[0158] In this example, 1i was used to replace 1a in Example 23 in equimolar amount, and eluent was petroleum ether / ethyl acetate (5:1 by volume), and other steps were the same as Example 23, to give bisboronate 3i as a white solid, with a yield of 59 mg, 82% yield. The corresponding monoboronate product was 4 mg, 8% yield.

[0159]

[0160] 3i: 1H NMR (400 MHz, CDCl3): δ = 7.65–7.52 (m, 2H), 7.23–7.15 (m, 2H),2.24 (s, 1H), 1.25 (s, 12H), 1.14 (s, 12H), 1.13 (s, 12H); 13 C NMR(100 MHz, CDCl3): δ = 152.9, 131.0, 130.0, 115.3, 83.6, 24.8, 24.7; 11 B NMR(128 MHz, CDCl3): δ = 34.07. HRMS (ESI + ): calcd for C 19 H 30 B2O5 + [M+H] + 361.2352,found 361.2357

[0161] Example 31

[0162] In this example, 1j was used to replace 1a in Example 23, and the eluent was petroleum ether / ethyl acetate (volume ratio of 20:1), and other steps were the same as Example 23, to obtain bisborate 3j in the form of white solid, with a yield of 70 mg and a yield of 74%. At this time, the yield of the corresponding monoborate product was 9 mg and the yield was 6%.

[0163]

[0164] 3j: 1 H NMR (400 MHz, CDCl3): δ = 7.65–7.52 (m, 2H), 7.23–7.15 (m, 2H),2.24 (s, 1H), 1.25 (s, 12H), 1.14 (s, 12H), 1.13 (s, 12H); 13 C NMR (100 MHz,CDCl3): δ = 143.5, 135.0, 134.7, 128.8, 128.6, 83.5, 25.0, 24.8, 24.7; 11 B NMR(128 MHz, CDCl3): δ = 32.13

[0165] Example 32

[0166] In this example, 1k was used to replace 1a in Example 23 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23 to obtain bisboronate 3k as a white solid in 48 mg in 67% yield. The corresponding monoboronate product was 17 mg in 8% yield at this time.

[0167]

[0168] 3k: 1 H NMR (400 MHz, CDCl3): δ = 7.45 (dd, J = 7.6, 1.4 Hz, 1H), 7.14–7.05 (m, 2H), 7.02–6.98 (m, 1H), 2.40 (s, 1H), 2.25 (s, 3H), 1.24 (s, 12H),1.23 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 138.3, 135.8, 129.8, 129.2,125.8, 124.5, 83.4, 24.9, 24.7, 20.8; 11 B NMR (128 MHz, CDCl3): δ = 32.68

[0169] Example 33

[0170] In this example, 1m was used to replace 1a in Example 23 in equimolar amount, and other steps were the same as Example 23 to obtain bisboronate 3m as a white solid in 58 mg in 75% yield. The corresponding monoboronate product was 9 mg in 18% yield at this time.

[0171]

[0172] 3m: 1 H NMR (400 MHz, CDCl3): δ = 7.09–7.02 (m, 2H), 6.64 (dt, J = 8.1,4.0 Hz, 1H), 3.79 (s, 3H), 2.42 (s, 1H), 2.12 (s, 3H), 1.24 (s, 12H), 1.23(s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 157.6, 139.7, 125.6, 124.5, 122.1,106.9, 83.4, 55.5, 24.9, 24.7, 12.2;11 B NMR (128 MHz, CDCl3): δ = 33.30. HRMS(ESI + ): calcd for C 21 H 24 B2O5 + [M+H] + 389.2665, found 389.2661

[0173] Example 34

[0174] In this example, 1n was used instead of 1a in Example 23, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to obtain bisboronate 3n as a white solid, with a yield of 66 mg and a yield of 76%. At this time, the corresponding monoboronate product was 6 mg in yield and 10% in yield.

[0175]

[0176] 3n: 1 H NMR (400 MHz, CDCl3): δ = 7.47 (d, J = 7.6 Hz, 1H), 7.27–7.19(m, 2H), 7.15 (td, J = 7.9, 5.9 Hz, 4H), 7.07–6.99 (m, 2H), 3.99 (s, 2H),2.46 (s, 1H), 1.19 (s, 12H), 1.18 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ =141.1, 138.5, 137.9, 130.4, 130.1, 129.1, 128.4, 126.2, 125.8, 124.5, 83.4,39.9, 24.8, 24.7; 11 B NMR (128 MHz, CDCl3): δ = 33.41. HRMS (ESI + ): calcd for C 26 H 36 B2O4 + [M+H] + 435.2872, found 435.2871

[0177] Example 35

[0178] In this example, 1o was used to replace 1a in Example 23, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to obtain the bisboronate 3o in the form of a white solid, with a yield of 61 mg and a yield of 70%. At this time, the corresponding monoboronate product was 9 mg in yield and 15% in yield.

[0179]

[0180] 3o: 1 H NMR (400 MHz, CDCl3): δ = 7.60–7.55 (m, 1H), 7.28–7.23 (m, 1H),7.19–7.11 (m, 6H), 2.44 (s, 1H), 2.37 (s, 3H), 1.21 (s, 24H); 13 C NMR (100MHz, CDCl3): δ = 141.6, 139.7, 137.5, 136.1, 130.0, 129.7, 129.5, 128.8,126.9, 124.2, 83.4, 24.81, 24.76, 21.3; 11 B NMR (128 MHz, CDCl3): δ = 32.62.HRMS (ESI + ): calcd for C 26 H 36 B2O4 + [M+H] + 435.2872, found 435.2870

[0181] Example 36

[0182] In this example, 1p was used to replace 1a in Example 23, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to obtain the bisboronate 3p in the form of a white solid, with a yield of 47 mg and a yield of 60%. At this time, the corresponding monoboronate product was 8 mg in yield and 15% in yield.

[0183]

[0184] 3p: 1H NMR (400 MHz, CDC13): δ = 7.78-7.67 (m, 4H), 7.47 (dd, J = 8.5, 1.8 Hz, 1H), 7.41-7.32 (m, 2H), 2.48 (s, 1H), 1.25 (s, 12H), 1.22 (s, 12H); 13 C NMR (100 MHz, CDC13): δ = 137.4, 133.9, 131.4, 129.0, 127.6, 127.5, 127.3, 126.6, 125.4, 124.4, 83.6, 24.8, 24.7; 11 B NMR (128 MHz, CDC13): δ = 32.61

[0185] Example 37

[0186] In this example, 1q was used to replace 1a in Example 23 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to obtain bisboronate 3q in white solid, with a yield of 56 mg and a yield of 71%. At this time, the corresponding monoboronate product was 7 mg in yield of 14%.

[0187]

[0188] 3q: 1 H NMR (400 MHz, CDC13): δ = 8.06 (d, J = 8.1 Hz, 1H), 7.86-7.75 (m, 1H), 7.65 (dd, J = 15.2, 7.7 Hz, 2H), 7.48-7.37 (m, 3H), 2.98 (s, 1H), 1.25 (s, 12H), 1.22 (s, 12H); 13 C NMR (100 MHz, CDC13): δ = 136.2, 134.1, 132.9, 128.7, 126.3, 125.9, 125.3, 125.1, 124.8, 124.5, 83.6, 24.9, 24.8; 11 B NMR (128 MHz, CDC13): δ = 33.58

[0189] Example 38

[0190] In this example, 1r was used to replace 1a in Example 23, and the eluent was petroleum ether / ethyl acetate (volume ratio of 20:1), and other steps were the same as Example 23, to obtain the bisboronate 3r in the form of a white solid, with a yield of 65 mg and a yield of 84%. At this time, the corresponding monoboronate product was 4 mg in yield and 8% in yield.

[0191]

[0192] 3r: 1 H NMR (400 MHz, CDCl3): δ = 7.52–7.47 (m, 2H), 7.42 (d, J = 8.0Hz, 1H), 7.12 (dd, J = 8.0, 1.3 Hz, 1H), 6.68 (dd, J = 2.1, 0.9 Hz, 1H), 2.41(s, 1H), 1.23 (s, 12H), 1.22 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 155.6,143.9, 136.3, 124.7, 124.0, 120.3, 111.8, 106.5, 83.6, 24.82, 24.75; 11 B NMR(128 MHz, CDCl3): δ = 33.52. HRMS (ESI + ): calcd for C 21 H 30 B2O5 + [M+H] + 385.2352,found 385.2354

[0193] Example 39

[0194] In this example, 1s was used to replace 1a in Example 23, and other steps were the same as Example 23, to obtain the bisboronate 3s in the form of a white solid, with a yield of 78 mg and a yield of 82%. At this time, the corresponding monoboronate product was 4 mg in yield and 6% in yield.

[0195]

[0196] 3s: 1H NMR (400 MHz, CDC13): δ = 7.43-7.38 (m, 2H), 7.33-7.27 (m, 2H), 7.12-7.06 (m, 2H), 6.89 (d, J = 8.3 Hz, 1H), 4.28 (s, 4H), 2.34 (s, 1H), 1.25 (s, 12H), 1.24 (s, 12H); 13 C NMR (100 MHz, CDC13): δ = 143.7, 142.7, 138.4, 136.4, 135.2, 129.6, 126.4, 112.0, 117.5, 115.6, 83.5, 64.5, 24.8, 24.7; 11 BNMR (128 MHz, CDC13): δ = 32.45. HRMS (ESI + ): calcd for C 27 H 36 B2O6 + [M+H] + 479.2771, found 479.2771

[0197] Example 40

[0198] In this example, equimolar of 1t was used to replace 1a in Example 23, and the eluent was petroleum ether / ethyl acetate (volume ratio 20:1), and other steps were the same as Example 23, to obtain a white solid of bisboronic ester 3t, yield 56 mg, yield 68%. At this time, the corresponding monoboronic ester product yield was 9 mg, yield 14%.

[0199]

[0200] 3t: 1 H NMR (400 MHz, CDC13): δ = 7.70-7.66 (m, 1H), 7.44 (t, J = 1.7 Hz, 1H), 7.36-7.33 (m, 2H), 7.30-7.24 (m, 2H), 6.67 (dd, J = 1.8, 0.8 Hz, 1H), 2.31 (s, 1H), 1.23 (s, 12H), 1.22 (s, 12H); 13C NMR (100 MHz, CDC13): δ = 143.5, 138.6, 138.1, 129.6, 128.4, 126.8, 125.7, 109.0, 83.6, 24.83, 24.74; 11 B NMR (128 MHz, CDC13): δ = 32.90. HRMS (ESI + ): calcd for C 23 H 32 B2O5 + [M+H] + 411.2509, found 411.2510

[0201] Example 41

[0202] In this example, equimolar of 1u was used to replace 1a in Example 23, the eluent was petroleum ether / ethyl acetate (volume ratio of 20:1), and other steps were the same as Example 23, to obtain the bisboronate 3u in the form of white solid, the yield was 64 mg, the yield was 75%. At this time, the corresponding monoboronate product yield was 5 mg, the yield was 8%.

[0203]

[0204] 3u: 1 H NMR (400 MHz, CDC13): δ = 7.49-7.44 (m, 2H), 7.40-7.36 (m, 2H), 7.34 (dd, J = 5.1, 2.8 Hz, 1H), 7.32-7.27 (m, 2H), 2.33 (s, 1H), 1.24 (s, 12H), 1.23 (s, 12H); 13 C NMR (100 MHz, CDC13): δ = 142.8, 138.8, 132.0, 129.6, 126.5, 126.2, 125.9, 119.2, 83.6, 24.8, 24.7; 11 B NMR (128 MHz, CDC13): δ = 33.50. HRMS (ESI + ): calcd for C 23 H 32 B2O4S + [M+H] + 427.2280, found 427.2285

[0205] Example 42

[0206] In this example, 1v was used to replace 1a in Example 23 in equimolar amount, the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to give the bisboronate 3v as a white solid in 56 mg in 81% yield. The corresponding monoboronate product was 5 mg in 12% yield at this time.

[0207]

[0208] 3v: 1 H NMR (400 MHz, CDCl3): δ = 7.29–7.18 (m, 4H), 7.10–7.04 (m, 1H),2.30 (s, 1H), 1.23 (s, 12H), 1.21 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ =139.6, 129.33, 128.1, 124.3, 83.5, 24.8, 24.7; 11 B NMR (128 MHz, CDCl3): δ =32.74

[0209] Example 43

[0210] In this example, 1w was used to replace 1a in Example 23 in equimolar amount, the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to give the bisboronate 3w as a white solid in 77 mg in 76% yield. The corresponding monoboronate product was 8 mg in 13% yield at this time.

[0211]

[0212] 3w: 1 H NMR (400 MHz, CDCl3): δ = 7.61–7.56 (m, 2H), 7.42 (d, J = 8.2Hz, 2H), 7.34 (d, J = 8.3 Hz, 2H), 7.27–7.22 (m, 2H), 2.36(s, 1H), 1.25 (s,12H), 1.23 (s, 12H); 13C NMR (100 MHz, CDC13): δ = 148.3 (d, J = 1.8). 140.4, 139.5, 135.7, 129.8, 128.2, 126.8, 121.2, 83.6, 24.83, 24.76; 11 B NMR (128 MHz, CDC13): δ = 33.16, 19F NMR (376 MHz, CDC13): δ = -57.80; HRMS (ESI + ): calcd for C 26 H 33 B2F3O5 + [M+H] + 505.2539, found 505.2540

[0213] Example 44

[0214] In this example, 1x was used to replace 1a in Example 23 with equimolar amount, and other steps were the same as Example 23, to give bisboronate 3x as a white solid, with a yield of 68 mg, 75% yield. The corresponding monoboronate product was 6 mg, 10% yield.

[0215]

[0216] 3x: 1 H NMR (400 MHz, CDC13): δ = 7.44-7.37 (m, 2H), 7.35-7.24 (m, 4H), 7.03-6.93 (m, 2H), 3.81 (s, 3H), 2.35 (s, 1H), 1.25 (s, 12H), 1.24 (s, 12H); 13 C NMR (100 MHz, CDC13): δ = 156.6, 138.3, 134.3, 131.0, 129.3, 129.0, 128.1, 120.9, 111.3, 83.5, 55.6, 24.84, 24.81; 11 B NMR (128 MHz, CDC13): δ = 32.89. HRMS (ESI + ): calcd for C 26 H 36 B2O5 + [M+H] + 451.2822, found 451.2818

[0217] Example 45

[0218] In this example, 1y was used to replace 1a in Example 23 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to obtain bisboronate 3y in white solid, with a yield of 58 mg and a yield of 77%. At this time, the yield of the corresponding monoboronate product was 3 mg and the yield was 5%.

[0219]

[0220] 3y: 1 H NMR (400 MHz, CDCl3): δ = 7.24–7.09 (m, 4H), 2.26 (s, 1H), 1.22(s, 12H), 1.21 (s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 138.3, 130.6, 130.0,128.1, 83.7, 24.8, 24.7; 11 B NMR (128 MHz, CDCl3): δ = 33.74

[0221] Example 46

[0222] In this example, 1z was used to replace 1a in Example 23 in equimolar amount, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23, to obtain bisboronate 3z in white solid, with a yield of 46 mg and a yield of 69%. At this time, the yield of the corresponding monoboronate product was 7 mg and the yield was 16%.

[0223]

[0224] 3z: 1 H NMR (400 MHz, CDCl3): δ = 7.35 (q, J = 1.2 Hz, 1H), 7.29 (t, J= 1.6 Hz, 1H), 6.30 (d, J = 0.9 Hz, 1H), 2.04 (s, 1H), 1.24 (s, 12H), 1.23(s, 12H); 13 C NMR (100 MHz, CDCl3): δ = 142.0, 139.4, 120.8, 112.9, 83.6,24.9, 24.7; 11B NMR (128 MHz, CDCl3): δ = 33.42

[0225] Example 47

[0226] In this example, 1aa was used to replace 1a in Example 23 with equimolar amount, and the eluent was petroleum ether / ethyl acetate (20:1 by volume), and other steps were the same as Example 23 to obtain bisboronate 3aa as a white solid with a yield of 43 mg and a yield of 61%. At this time, the corresponding monoboronate product was obtained with a yield of 2 mg and a yield of 4%.

[0227]

[0228] 3aa: 1 H NMR (400MHz, CDCl3): δ = 7.17 (dd, J = 4.9, 3.0 Hz, 1H), 7.07-7.03 (m, 1H), 6.98 (dd, J = 4.9, 1.1 Hz, 1H), 2.38 (s, 1H), 1.24 (s, 12H), 1.23 (s, 12H); 13 C NMR (100MHz, CDCl3): δ = 138.1, 130.0, 124.1, 119.7, 83.6, 24.9, 24.7; 11 B NMR (128MHz, CDCl3): δ = 33.48

[0229] Comparative Example 1

[0230] The ligand 4,4'-dimethylbipyridine (4 mg, 0.02 mmol) was used to replace the ligand 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine (8 mg, 0.02 mmol) in Example 1, and other steps were the same as Example 1 to obtain monoboronate product 2a (yield of 14 mg, yield of 28%) and bisboronate product 3a (yield of 4 mg, yield of 5%).

[0231] Comparative Example 2

[0232] The ligand 4,4'-dimethylbipyridine (4 mg, 0.02 mmol) was used to replace the ligand 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine (8 mg, 0.02 mmol) in Example 1, and other steps were the same as Example 1 to obtain monoboronate product 2a (yield of 14 mg, yield of 28%) and bisboronate product 3a (yield of 4 mg, yield of 5%).

[0233] Comparative Example 3

[0234] Replace ligand 4,4',4"-tri-tert-butyl-2,2':6',2" terpyridine (8 mg, 0.02 mmol) with ligand 5,5'-dimethylbipyridine (4 mg, 0.02 mmol) in Example 1, other steps are the same as Example 1, to obtain mono-boronate product 2a (yield 12 mg, 24%) and bis-boronate product 3a (yield 4 mg, 5%).

[0235] Comparative Example 4

[0236] Replace ligand 4,4',4"-tri-tert-butyl-2,2':6',2" terpyridine (8 mg, 0.02 mmol) with ligand 6,6'-dimethylbipyridine (4 mg, 0.02 mmol) in Example 1, other steps are the same as Example 1, to obtain mono-boronate product 2a (yield 18 mg, 36%) and bis-boronate product 3a (yield 19 mg, 25%).

[0237] Comparative Example 5

[0238] Replace ligand 4,4',4"-tri-tert-butyl-2,2':6',2" terpyridine (8 mg, 0.02 mmol) with ligand 2,2':6',2" terpyridine (5 mg, 0.02 mmol) in Example 1, other steps are the same as Example 1, to obtain mono-boronate product 2a (yield 32 mg, 65%) and bis-boronate product 3a (yield 16 mg, 22%).

[0239] Comparative Example 6

[0240] Replace ligand 4,4',4"-tri-tert-butyl-2,2':6',2" terpyridine (8 mg, 0.02 mmol) with ligand 2,2' biquinoline (5 mg, 0.02 mmol) in Example 1, other steps are the same as Example 1, to obtain mono-boronate product 2a (yield 3 mg, 7%) and bis-boronate product 3a (yield 3 mg, 4%).

[0241] Comparative Example 7

[0242] Replace catalyst chromium dichloride (2.5 mg, 0.02 mmol) with catalyst chromium trichloride (3 mg, 0.02 mmol) in Example 1, other steps are the same as Example 1, to obtain mono-boronate product 2a (yield 30 mg, 61%) and bis-boronate product 3a (yield 7 mg, 10%).

[0243] Comparative Example 8

[0244] The procedure of Example 1 was followed using catalyst chromium acetylacetonate (7 mg, 0.02 mmol) instead of catalyst chromium dichloride (2.5 mg, 0.02 mmol) to give mono-boronate product 2a (yield 13 mg, 27%) and di-boronate product 3a (yield 4 mg, 5%).

[0245] Comparative Example 9

[0246] The procedure of Example 1 was followed using catalyst chromium dichloride (1.3 mg, 0.01 mmol) instead of catalyst chromium dichloride (2.5 mg, 0.02 mmol) to give mono-boronate product 2a (yield 23 mg, 47%) and di-boronate product 3a (yield 5 mg, 7%).

[0247] Comparative Example 10

[0248] The procedure of Example 1 was followed using catalyst chromium dichloride (3.9 mg, 0.03 mmol) instead of catalyst chromium dichloride (2.5 mg, 0.02 mmol) to give mono-boronate product 2a (yield 41 mg, 83%) and di-boronate product 3a (yield 9 mg, 13%).

[0249] Comparative Example 11

[0250] The procedure of Example 1 was followed using catalyst chromium dichloride (5 mg, 0.04 mmol) instead of catalyst chromium dichloride (2.5 mg, 0.02 mmol) to give mono-boronate product 2a (yield 42 mg, 85%) and di-boronate product 3a (yield 9 mg, 12%).

[0251] Comparative Example 12

[0252] The procedure of Example 1 was followed using 4 equivalents of pinacol borane (116 μL, 0.8 mmol) instead of 5 equivalents of pinacol borane (145 μL, 1.0 mmol) to give mono-boronate product 2a (yield 37 mg, 75%) and di-boronate product 3a (yield 12 mg, 17%).

[0253] Comparative Example 13

[0254] Replace 5 equivalents of pinacolborane (145 μL, 1.0 mmol) and 4 equivalents of magnesium (19 mg, 0.8 mmol) in Example 1 with 4 equivalents of pinacolborane (116 μL, 0.8 mmol) and 5 equivalents of magnesium (24 mg, 1.0 mmol), and the other steps are the same as Example 1 to obtain mono-boronate product 2a (yield 37 mg, 75%) and di-boronate product 3a (yield 14 mg, 19%).

[0255] Comparative Example 14

[0256] Replace lithium chloride as an additive in Example 23 with no addition of lithium chloride, and the other steps are the same as Example 23 to obtain mono-boronate product 2a (yield 10 mg, 18%) and di-boronate product 3a (yield 55 mg, 74%).

[0257] Comparative Example 15

[0258] Replace the temperature 40 °C reaction in Example 23 with a temperature of 60 °C, and the other steps are the same as Example 23 to obtain mono-boronate product 2a (yield 5 mg, 9%) and di-boronate product 3a (yield 55 mg, 73%).

[0259] Comparative Example 16

[0260] Replace the temperature 40 °C reaction in Example 23 with a temperature of 80 °C, and the other steps are the same as Example 23 to obtain mono-boronate product 2a (yield 5.5 mg, 11%) and di-boronate product 3a (yield 50 mg, 67%).

[0261] Comparative Example 17

[0262] Replace the temperature 40 °C reaction in Example 23 with a temperature of 100 °C, and the other steps are the same as Example 23 to obtain mono-boronate product 2a (yield 5.5 mg, 11%) and di-boronate product 3a (yield 45 mg, 61%).

[0263] Comparative Example 18

[0264] Replace 4 equivalents of pinacol borane (116 μL, 0.8 mmol) and 3 equivalents of magnesium (14 mg, 0.6 mmol) in Example 23 with 4 equivalents of pinacol borane (116 μL, 0.8 mmol) and 4 equivalents of magnesium (19 mg, 0.8 mmol), and follow the same procedure as Example 23 to obtain mono-boronate product 2a (5 mg, 10% yield) and di-boronate product 3a (64 mg, 85% yield).

[0265] In the description of the present specification, the description of the terms "one embodiment", "an example", "a specific example" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Also, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in an appropriate manner.

[0266] The preferred embodiments of the application disclosed above are only used to help explain the present application. The preferred embodiments do not describe all the details of the application, and the application is not limited to the specific embodiments described. Obviously, many modifications and variations can be made according to the content of the present specification. The present specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present application, so that those skilled in the art can well understand and utilize the present application. The present application is limited only by the claims and their full scope and equivalents.

Claims

1. A process for the chromium-catalyzed preparation of a benzylic boronic acid ester compound, characterized in that, The method comprises: under an inert atmosphere, performing a deoxy-borination reaction of aryl carboxylate and pinacol borane in the presence of a chromium catalyst, a ligand and magnesium element in a tetrahydrofuran solvent to generate benzyl monoboronic acid ester or benzylidene diboronic acid ester; The structural general formula of the aryl carboxylate, benzyl monoboronic acid ester and benzylidene diboronic acid ester is as follows: 、 、 The Ar is selected from the following groups: 4-methoxyphenyl, 4-methylphenyl, 4-tert-butylphenyl, 4-phenylphenyl, 4-((4-n-propyl)cyclohexyl)phenyl, 4-((4-trimethylsilyl)phenyl)phenyl, 4-((dimethyl tert-butyl silyl)oxy)phenyl, 4-phenoxyphenyl, 4-hydroxyphenyl, 4-pinacol boron phenyl, 2-methylphenyl, 2,5-dimethylphenyl, 2-methyl-3-methoxyphenyl, 2-ethoxyphenyl, 2-benzylphenyl, 2-(4-methylphenyl)phenyl, 2-naphthyl, 1-naphthyl, 6-benzofuranyl, 4-benzo(1,4)cyclohexadienylphenyl, 4-(3-furyl)phenyl, 4-(3-thiophenyl)phenyl, phenyl, 4-((4-trifluoromethoxy)phenyl)phenyl, 4-(2-methoxyphenyl)phenyl, 4-chlorophenyl, 3-furyl, 3-thiophenyl; The R is selected from: methyl, ethyl, tert-butyl, phenyl.

2. The method of claim 1, wherein, The chromium catalyst is selected from at least one of: chromium dichloride, chromium trichloride, and acetylacetone chromium.

3. The method of claim 1, wherein, The ligand is selected from at least one of: 4,4'-di-tert-butyl-2,2':6',2''-terpyridine, 4,4'-di-tert-butyl-6,6'-dimethyl-2,2':6',2''-terpyridine, 4,4'-dimethyl-2,2':6',2''-terpyridine, 5,5'-dimethyl-2,2':6',2''-terpyridine, 6,6'-dimethyl-2,2':6',2''-terpyridine, 2,2':6',2''-terpyridine, 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine, 2,2'-biquinoline.

4. The method of claim 3, wherein, When the method is used to prepare benzyl monoboronic acid ester, the ligand is preferably 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine.

5. The method of claim 3, wherein, When the method is used to prepare benzylidene diboronic acid ester, the ligand is preferably 4,4'-di-tert-butyl-6,6'-dimethyl-2,2':6',2''-terpyridine, and lithium chloride is added as an additive.

6. The method of claim 1, wherein, The chromium catalyst and the ligand are added in an amount of 5-20% of the molar amount of the aryl carboxylate.

7. The method of claim 1, wherein, The magnesium element is added in an amount of 1-5 times the molar amount of the aryl carboxylate.

8. The method of claim 1, wherein, The reaction temperature of the deoxy-borination reaction is 40-100°C, preferably 80°C when preparing the benzyl monoboronic acid ester, and preferably 40°C when preparing the benzylidene diboronic acid ester.

Images