A method for preparing a chiral borate compound

Abstract

The present invention discloses a preparation method of chiral borate compounds. The method comprises: under the atmosphere of an inert gas, adding a photosensitizer, a nickel catalyst, a chiral ligand, a base, a reducing agent, and an additive into water and an organic solvent, and then reacting; under the atmosphere of an inert gas, adding an α-chloroborate compound (I) and an alkyl iodide (II) to the above reaction solution, and reacting under the irradiation of blue light to obtain a chiral borate compound. The present invention realizes the reductive cross-coupling of an alkyl iodide and an α-chloroborate under photo / nickel redox catalysis, and obtains chiral borate compounds. This method has many advantages such as high reaction efficiency, mild reaction conditions, good atom economy, high yield, excellent functional group compatibility, and excellent substrate generality.

Description

Technical Field

[0001] The present invention relates to the technical field of the synthesis of borate compounds, and relates to a preparation method of chiral borate compounds. Background Art

[0002] Organic borides refer to organic compounds containing carbon-boron bonds. In recent years, the research on organic borides has become increasingly popular, and the discipline of organoboron chemistry has gradually developed. Organic borides have a wide range of applications in the fields of materials science, life science, pharmaceutical science, and organic synthesis. Among them, chiral borate compounds have important application values in organic synthesis and pharmaceutical synthesis because the borate functional groups therein can be easily converted into a series of other functional groups.

[0003] In the existing methods for synthesizing such chiral borates, organometallic reagents that are sensitive to air and moisture are often required, resulting in poor compatibility of many functional groups in these synthesis methods.

[0004] Therefore, it is of great practical significance to develop a preparation method of chiral borate compounds with mild synthesis conditions and good functional group compatibility. Summary of the Invention

[0005] Due to the defects of the existing technology that the preparation conditions of chiral borates are harsh and the functional group compatibility is poor, the present invention provides a preparation method of chiral borate compounds with mild synthesis conditions and good functional group compatibility.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] A preparation method of chiral borate compounds, the steps are as follows:

[0008] (1) Under the atmosphere of an inert gas, a photosensitizer, a nickel catalyst, a chiral ligand, a base, a reducing agent, and an additive are added to water and an organic solvent and then reacted;

[0009] (2) Under the atmosphere of an inert gas, an α-chloroborate compound (I) and an alkyl iodide (II) are added to the above reaction solution, and the reaction is carried out under the irradiation of blue light to obtain a chiral borate compound.

[0010]

[0011] R 1 、R 2 are alkyl, substituted alkyl or aryl.

[0012] Under photo / nickel redox catalysis, the present invention realizes the reductive cross-coupling of alkyl iodides and α-chloroboronates to obtain chiral boronate compounds. This method has many advantages such as high reaction efficiency, mild reaction conditions, good atom economy, high yield, excellent functional group compatibility, and substrate generality.

[0013] As a preferred technical solution:

[0014] In the preparation method as described above, the inert gas is nitrogen, helium, neon, or argon;

[0015] The organic solvent is one or a mixture of two or more of N,N'-dimethylacetamide, trifluorotoluene, 1,4-dioxane, 1,2-dichloroethane, tetrahydrofuran, ethylene glycol dimethyl ether, acetonitrile, acetone, diethylene glycol dimethyl ether, N,N'-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, 1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone, toluene, ethyl acetate, dimethyl sulfoxide, cyclopentyl methyl ether, diethyl ether, methyl tert-butyl ether, chloroform, and dichloromethane;

[0016] The photosensitizer is 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile (4CzIPN), 2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile (3DPAFIPN`), ruthenium(III) chloride hexahydrate [Ru(bpy) 3 Cl 2 ·6H 2 O], tris(2-(4-trifluoromethylphenyl)pyridine)iridium [fac-Ir(ppy) 3 , and bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2,2'-bi(4-tert-butylpyridine)]iridium bis(hexafluorophosphate) {[Ir(dF(CF 3 )ppy) 2 (dtbbpy)]PF 6}, or a mixture of two or more of them;

[0017] The nickel catalyst is nickel(II) bromide diglyme (NiBr 2 ·diglyme), nickel(II) bromide DME (NiBr 2 ·DME), bis(1,5-cyclooctadiene)nickel(0) [Ni(COD) 2 , nickel(II) chloride DME (NiCl 2 ·DME), nickel(II) bromide (NiBr 2 ), nickel(II) iodide (NiI 2 ), nickel(II) chloride (NiCl 2 ), nickel(II) acetylacetonate [Ni(acac) 2and nickel(II) perchlorate hexahydrate [Ni(ClO 4 ) 2 ·6H 2 O] or a mixture of two or more of them;

[0018] The chiral ligand is ligand (L1), (1R,2R)-N,N'-dimethyl-1,2-diphenylethane-1,2-diamine, (4S,4'S)-4,4',5,5'-tetrahydro-4,4'-diphenyl-2,2'-biisoxazole, (4S,4'S)-2,2'-isopropylidene bis(4-phenyl-2-oxazoline), and (4S,4'S)-2,2'-cyclopropylidene bis[4,5-dihydro-4-phenyloxazole], or a mixture of two or more of them. The structural formula of ligand (L1) is

[0019]

[0020] The base is sodium bicarbonate, lithium carbonate, sodium carbonate, potassium bicarbonate, lithium phosphate, cesium carbonate, potassium phosphate, potassium dihydrogen phosphate, cesium fluoride, potassium fluoride, sodium fluoride, dipotassium hydrogen phosphate, sodium trifluoroacetate, potassium acetate, sodium acetate, cesium acetate, triethylamine (TEA), N,N,N',N'-tetramethylethylenediamine (TMEDA), and tetramethylguanidine (TMG), or a mixture of two or more of them;

[0021] The reducing agent is diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate (HEH), zinc (Zn), manganese (Mn), magnesium (Mg), samarium (Sm), tetrakis(dimethylamino)ethylene (TDAE), bis(pinacolato)diboron (B 2 Pin 2 ), triethylamine (TEA), N,N,N',N'-tetramethylethylenediamine (TMEDA), and tetramethylguanidine (TMG), or a mixture of two or more of them;

[0022] The additive is magnesium trifluoromethanesulfonate, magnesium chloride, magnesium ethoxide, zinc trifluoromethanesulfonate, lithium bromide, sodium iodide, tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride (TBAC), tetrabutylammonium iodide (TBAI), vitamin B12, zinc bromide, zinc chloride, magnesium bromide hexahydrate, and magnesium perchlorate hexahydrate, or a mixture of two or more of them.

[0023] In the preparation method as described above, the organic solvent is a mixed solvent of N,N'-dimethylacetamide and trifluorotoluene;

[0024] The photosensitizer is 2,4,5,6-tetra(9-carbazolyl) isophthalonitrile (4CzIPN);

[0025] The nickel catalyst is nickel(II) bromide bis(diethylene glycol dimethyl ether) (NiBr2 · diglyme);

[0026] The chiral ligand is ligand (L1);

[0027] The base is sodium bicarbonate;

[0028] The reducing agent is diethyl 2,6 - dimethyl - 1,4 - dihydropyridine - 3,5 - dicarboxylate (HEH);

[0029] The additive is magnesium trifluoromethanesulfonate.

[0030] In the preparation method as described above, in step (1), the reaction temperature of the reaction is 0 - 150 °C, and the reaction time is 0.1 - 12 h;

[0031] The photosensitizer is 1 - 100% molar equivalent of alkyl iodide (II), the nickel catalyst is 1 - 100% molar equivalent of alkyl iodide (II), the chiral ligand is 1 - 100% molar equivalent of alkyl iodide (II), the base is 50 - 500% molar equivalent of alkyl iodide (II), the reducing agent is 50 - 500% molar equivalent of alkyl iodide (II), and the additive is 50 - 500% molar equivalent of alkyl iodide (II);

[0032] In step (2), the reaction temperature of the reaction is 0 - 150 °C, and the reaction time is 1 - 12 h;

[0033] The dosage of the α - chloroborate (I) is 100 - 500% molar equivalent of alkyl iodide (II).

[0034] In the preparation method as described above, in step (1), the reaction temperature of the reaction is 20 - 30 °C, and the reaction time is 60 - 90 min;

[0035] The photosensitizer is 2% molar equivalent of alkyl iodide (II), the nickel catalyst is 10% molar equivalent of alkyl iodide (II), the chiral ligand is 20% molar equivalent of alkyl iodide (II), the base is 250% molar equivalent of alkyl iodide (II), the reducing agent is 250% molar equivalent of alkyl iodide (II), and the additive is 200% molar equivalent of alkyl iodide (II);

[0036] In step (2), the reaction temperature of the reaction is 20 - 30 °C, and the reaction time is 2 - 6 h;

[0037] The dosage of the α - chloroborate (I) is 150 - 200% molar equivalent of alkyl iodide (II).

[0038] In the preparation method as described above, the power of the blue light is 30 W.

[0039] In the preparation method as described above, after the reaction in step (2) is completed, the product is washed, extracted, concentrated, purified and separated.

[0040] The product obtained by the above-mentioned preparation method is a compound having the structure shown in the following formula, its enantiomeric structure and its racemic structure;

[0041]

[0042] Among them, R 1 , R 2 is an alkyl group, a substituted alkyl group or an aryl group, and the structural formula of BPin is as follows:

[0043]

[0044] Specifically, the specific structural formula of the product is:

[0045]

[0046] Wherein Ph is phenyl.

[0047] The above invention has the following advantages or beneficial effects:

[0048] The present invention realizes the reductive cross-coupling of alkyl iodide and α-chloroborate under light / nickel redox catalysis to obtain chiral borate compounds. This method has many advantages such as high reaction efficiency, mild reaction, high yield, good atom economy, excellent functional group compatibility and substrate universality. DETAILED DESCRIPTION

[0049] The present invention will be further described below in conjunction with specific embodiments, but they are not intended to limit the present invention.

[0050] The specific structural formula of the ligand (L1) in the following examples is as follows:

[0051]

[0052] Example 1

[0053] Preparation:

[0054] In a glove box, photosensitizer 4CzIPN (0.002 mmol, 0.0016 g), nickel catalyst NiBr 2·Diglyme, nickel(II) bromide (0.01 mmol, 0.0036 g), ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), reducing agent HEH diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (0.25 mmol, 0.0632 g), additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g) were added via syringe to N,N'-dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL). Then the Schlenk tube was removed from the glove box and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. After that, under a nitrogen atmosphere, α-chloroborate (0.15 mmol, 0.0348 g) and (0.10 mmol, 0.0334 g) were added using a microsyringe. After addition, the Schlenk tube was closed again and the reaction mixture was stirred and irradiated with blue light (λ = 450 - 455 nm) for 2 - 6 hours. Meanwhile, the temperature was controlled at 20 - 30 °C using a fan and air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered through diatomaceous earth, and concentrated in vacuo. It was separated by column chromatography to obtain 0.0295 g of product with a yield of 73% and an ee value of 98%.

[0055] 1 1H NMR (600 MHz, CDCl 3 ) δ 7.99 (d, J = 9.0 Hz, 2H), 6.90 (d, J = 9.0 Hz, 2H), 4.27 (t, J = 6.6 Hz, 2H), 3.86 (s, 3H), 1.79 - 1.70 (m, 2H), 1.51 - 1.39 (m, 5H), 1.31 - 1.25 (m, 5H), 1.23 (s, 12H), 1.02 - 0.93 (m, 1H), 0.87 (t, J = 7.2 Hz, 3H).;

[0056] 13 13C NMR (151 MHz, CDCl 3 ) δ 166.4, 163.2, 131.5, 123.0, 113.5, 82.8, 64.8, 55.4, 31.5, 31.1, 31.0, 29.1, 25.7, 24.8, 24.8, 23.0, 14.1.

[0057] HRMS: m / z (ESI) calculated [M+H] + : 405.2807, found: 405.2808.

[0058] Example 2

[0059] Preparation:

[0060] In a glove box, the photosensitizer 4CzIPN (0.002 mmol, 0.0016 g), nickel catalyst NiBr 2 ·diglyme nickel(II) bromide (0.01 mmol, 0.0036 g), ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), reducing agent HEH diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (0.25 mmol, 0.0632 g), additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g) were successively added to a dry Schlenk tube. N,N'-dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL) was added via a syringe. Then the Schlenk tube was removed from the glove box, and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. Then, under a nitrogen atmosphere, α-chloroborate (0.15 mmol, 0.0348 g) and (0.10 mmol, 0.0338 g) were added using a microsyringe. After addition, the Schlenk tube was closed again, and the reaction mixture was stirred and irradiated with blue light (λ = 450 - 455 nm) for 2 - 6 hours. Meanwhile, the temperature was controlled at 20 - 30 °C by a fan and an air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous Na 2 SO 4 dried, filtered through diatomaceous earth, and concentrated in vacuo. Separated by column chromatography to obtain 0.0249 g of the product The yield was 61% and the ee value was 97%.

[0061] 1 1H NMR (400 MHz, CDCl 3)δ 7.97 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.8 Hz, 2H), 4.30 (t, J = 6.4 Hz, 2H), 1.81 - 1.70 (m, 2H), 1.51 - 1.36 (m, 5H), 1.28 - 1.25 (m, 5H), 1.22 (s, 12H), 1.02 - 0.93 (m, 1H), 0.87 (t, J = 6.4 Hz, 3H);

[0062] 13 C NMR (101 MHz, CDCl 3 )δ 165.8, 139.2, 130.9, 128.6, 82.9, 65.4, 31.5, 31.1, 31.0, 29.0, 25.7, 24.8, 24.8, 23.0, 14.1.

[0063] HRMS: m / z (ESI) calculated [M+Na] + : 431.2131, found: 431.2134.

[0064] Example 3

[0065] Preparation:

[0066] In a glove box, the photosensitizer 4CzIPN (0.002 mmol, 0.0016 g), nickel catalyst NiBr 2 ·diglyme nickel bromide bis(diethylene glycol dimethyl ether) (0.01 mmol, 0.0036 g), ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), reducing agent HEH diethyl 2,6 - dimethyl - 1,4 - dihydropyridine - 3,5 - dicarboxylate (0.25 mmol, 0.0632 g), additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g) were successively added to a dry Schlenk tube. N,N’ - dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL) was added via a syringe. Then the Schlenk tube was removed from the glove box, and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. Then, under a nitrogen atmosphere, α - chloroborate (0.15 mmol, 0.0348 g) and (0.10 mmol, 0.0329 g). After addition, the Schlenk tube was closed again, and the reaction mixture was stirred and irradiated under blue light (λ = 450 - 455 nm) for 2 - 6 hours. Meanwhile, the temperature was controlled at 20 - 30 °C by a fan and an air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous Na 2 SO 4 and filtered through diatomaceous earth, then concentrated in vacuo. It was separated by column chromatography to obtain 0.0120 g of the product with a yield of 30% and an ee value of 94%.

[0067] 1 H NMR (600 MHz, CDCl 3 ) δ 8.14 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 4.34 (t, J = 6.6 Hz, 2H), 1.83 - 1.73 (m, 2H), 1.51 - 1.38 (m, 5H), 1.37 - 1.25 (m, 5H), 1.23 (s, 12H), 1.02 - 0.94 (m, 1H), 0.87 (t, J = 7.2 Hz, 3H).

[0068] 13 C NMR (151 MHz, CDCl 3 ) δ 165.0, 134.3, 132.1, 130.0, 118.0, 116.2, 82.9, 65.9, 31.4, 31.0, 31.0, 28.9, 25.64, 24.8, 24.7, 22.9, 14.1.

[0069] HRMS: m / z (ESI) calculated [M] + : 399.2575, found: 399.2572.

[0070] Example 4

[0071] Preparation:

[0072] In the glove box, the photosensitizer 4CzIPN (0.002 mmol, 0.0016 g) and the nickel catalyst NiBr 2·Diglyme, nickel(II) bromide (0.01 mmol, 0.0036 g), ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), reducing agent HEH diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (0.25 mmol, 0.0632 g), additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g) were added via syringe to N,N'-dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL). Then the Schlenk tube was removed from the glove box and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. After that, under a nitrogen atmosphere, α-chloroborate (0.15 mmol, 0.0348 g) and (0.10 mmol, 0.0372 g) were added using a microsyringe. After addition, the Schlenk tube was closed again and the reaction mixture was stirred and irradiated with blue light (λ = 450 - 455 nm) for 2 - 6 hours. Meanwhile, the temperature was controlled at 20 - 30 °C by a fan and air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted 3 times with ethyl acetate. The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered through diatomaceous earth, and concentrated in vacuo. It was separated by column chromatography to give 0.0278 g of the product with a yield of 63% and an ee value of 98%.

[0073] 1 1H NMR (600 MHz, CDCl 3 ) δ 8.29 (s, 1H), 8.23 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.58 (t, J = 7.8 Hz, 1H), 4.35 (t, J = 6.6 Hz, 2H), 1.84 - 1.73 (m, 2H), 1.52 - 1.39 (m, 5H), 1.30 - 1.23 (m, 5H), 1.22 (s, 12H), 1.04 - 0.95 (m, 1H), 0.87 (t, J = 7.2 Hz, 3H).

[0074] 13 13C NMR (151 MHz, CDCl 3)δ165.3,132.8,131.4,131.0(q, J = 32.8 Hz),129.3(q, J = 3.8 Hz),128.9,126.4(q, J = 3.8 Hz),123.7(q, J = 272.4 Hz),82.8,65.7,31.5,31.0,31.0,28.9,25.7,24.7,24.7,22.9,14.1.

[0075] HRMS: m / z (ESI) calculated [M+Na] + : 465.2394, found: 465.2388.

[0076] Example 5

[0077] Preparation:

[0078] In a glove box, the photosensitizer 4CzIPN (0.002 mmol, 0.0016 g), nickel catalyst NiBr 2 ·diglyme nickel dibromide (0.01 mmol, 0.0036 g), ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), reducing agent HEH diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (0.25 mmol, 0.0632 g), additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g) were successively added to a dry Schlenk tube. N,N'-dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL) was added via a syringe. Then the Schlenk tube was removed from the glove box, and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. Then, under a nitrogen atmosphere, α-chloroborate (0.15 mmol, 0.0348 g) and (0.10 mmol, 0.0315 g) were added using a microsyringe. After addition, the Schlenk tube was closed again, and the reaction mixture was stirred and irradiated with blue light (λ = 450 - 455 nm) for 2 - 6 hours. Meanwhile, the temperature was controlled at 20 - 30 °C by a fan and an air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous Na 2 SO 4 dried, filtered through diatomaceous earth, and concentrated in vacuo. It was separated by column chromatography to obtain 0.0212 g of the product with a yield of 55% and an ee value of 94%.

[0079] 1 H NMR (600 MHz, CDCl 3 ) δ 7.83 (dd, J = 5.4, 3.0 Hz, 2H), 7.70 (dd, J = 5.4, 3.0 Hz, 2H), 3.66 (t, J = 7.2 Hz, 2H), 1.73 - 1.62 (m, 2H), 1.50 - 1.34 (m, 4H), 1.34 - 1.25 (m, 4H), 1.22 (s, 12H), 1.00 - 0.96 (m, 1H), 0.86 (t, J = 7.2 Hz, 3H).

[0080] 13 C NMR (151 MHz, CDCl 3 ) δ 168.4, 133.7, 132.2, 123.1, 82.9, 38.3, 31.4, 30.9, 29.7, 28.5, 28.2, 24.8, 24.7, 22.9, 14.0.

[0081] HRMS: m / z (ESI) calculated [M + H] + : 386.2497, found: 386.2506

[0082] Example 6

[0083] Preparation:

[0084] In a glove box, the photosensitizer 4CzIPN (0.002 mmol, 0.0016 g), nickel catalyst NiBr 2 ·diglyme nickel(II) bromide (0.01 mmol, 0.0036 g), ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), reducing agent HEH diethyl 2,6 - dimethyl - 1,4 - dihydropyridine - 3,5 - dicarboxylate (0.25 mmol, 0.0632 g), additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g) were successively added to a dry Schlenk tube. N,N’ - dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL) was added via a syringe. Then the Schlenk tube was removed from the glove box, and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. Thereafter, under a nitrogen atmosphere, α - chloroborate (0.15 mmol, 0.0348 g) and (0.10 mmol, 0.0348 g). After addition, the Schlenk tube was closed again, and the reaction mixture was stirred and irradiated under blue light (λ = 450 - 455 nm) for 2 - 6 h. Meanwhile, the temperature was controlled at 20 - 30 °C by a fan and an air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered through diatomaceous earth, and concentrated in vacuo. It was separated by column chromatography to obtain 0.0167 g of the product The yield was 40% and the ee value was 96%.

[0085] 1 H NMR (600 MHz, CDCl 3 ) δ 7.49 (s, 1H), 4.04 - 3.94 (s, 5H), 3.56 (s, 3H), 1.73 - 1.61 (m, 2H), 1.50 - 1.25 (m, 8H), 1.23 (s, 12H), 1.00 - 0.95 (m, 1H), 0.86 (t, J = 7.2 Hz, 3H).

[0086] 13 C NMR (151 MHz, CDCl 3 ) δ 155.3, 151.4, 148.6, 141.2, 107.7, 82.8, 41.6, 33.5, 31.5, 30.8, 29.7, 29.6, 28.5, 27.7, 24.8, 24.7, 22.9, 14.1.

[0087] HRMS: m / z (ESI) calculated [M + H] + : 419.2824, found: 419.2822

[0088] Example 7

[0089] Preparation:

[0090] In the glove box, the photosensitizer 4CzIPN (0.002 mmol, 0.0016 g) and the nickel catalyst NiBr 2·Diglyme, nickel(II) bromide (0.01 mmol, 0.0036 g), ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), reducing agent HEH diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (0.25 mmol, 0.0632 g), additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g) were added via syringe to N,N'-dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL). Then the Schlenk tube was removed from the glove box and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. After that, under a nitrogen atmosphere, α-chloroborate (0.20 mmol, 0.0380 g) and (0.10 mmol, 0.0304 g) were added using a microsyringe. After addition, the Schlenk tube was closed again and the reaction mixture was stirred and irradiated with blue light (λ = 450 - 455 nm) for 2 - 6 hours. Meanwhile, the temperature was controlled at 20 - 30 °C using a fan and air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted 3 times with ethyl acetate. The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered through diatomaceous earth, and concentrated in vacuo. It was separated by column chromatography to obtain 0.0169 g of the product with a yield of 51% and an ee value of 97%.

[0091] 1 1H NMR (400 MHz, CDCl 3 ) δ 8.04 (d, J = 7.2 Hz, 1H), 7.54 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 4.31 (t, J = 6.8 Hz, 1H), 1.80 - 1.72 (m, 2H), 1.55 - 1.31 (m, 4H), 1.22 (s, 12H), 1.08 - 0.95 (m, 4H).

[0092] 13 13C NMR (101 MHz, CDCl 3 ) δ 166.7, 132.7, 130.6, 129.5, 128.3, 82.8, 65.1, 32.9, 29.0, 25.4, 24.7, 24.7, 15.5.

[0093] HRMS: m / z (ESI) calculated [M + H] + : 333.2232, found: 332.2228.

[0094] Example 8

[0095] Preparation:

[0096] In a glove box, to a dry Schlenk tube were successively added photosensitizer 4CzIPN (0.002 mmol, 0.0016 g), nickel catalyst NiBr 2 ·diglyme nickel(II) bromide (0.01 mmol, 0.0036 g), ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), reducing agent HEH diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (0.25 mmol, 0.0632 g), additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g). N,N'-dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL) was added via a syringe. Then the Schlenk tube was removed from the glove box, and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. After that, under a nitrogen atmosphere, α-chloroborate (0.15 mmol, 0.0399 g) and (0.10 mmol, 0.0304 g) were added using a microsyringe. After addition, the Schlenk tube was closed again, and the reaction mixture was stirred and irradiated with blue light (λ = 450 - 455 nm) for 2 - 6 hours. Meanwhile, the temperature was controlled at 20 - 30 °C by a fan and an air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous Na 2 SO 4 and filtered through diatomaceous earth, then concentrated in vacuo. It was separated by column chromatography to obtain 0.0175 g of the product with a yield of 43% and an ee value of 93%.

[0097] 1 1H NMR (600 MHz, CDCl 3 ) δ8.04 (d, J = 8.4 Hz, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 7.8 Hz, 2H), 4.31 (t, J = 6.6 Hz, 2H), 3.52 (t, J = 6.6 Hz, 2H), 1.81 - 1.72 (m, 4H), 1.53 - 1.30 (m, 8H), 1.22 (s, 12H), 1.04 - 0.97 (m, 1H).

[0098] 1313C NMR(151MHz,CDCl 3 )δ166.7,132.8,130.5,129.5,128.3,83.0,65.0,45.1,32.8,30.5,29.7,29.0,26.4,25.7,24.8.

[0099] HRMS:m / z(ESI)calculated[M+H]+:409.2311,found:409.2306.

[0100] Example 9

[0101] Preparation:

[0102] In a glove box, the photosensitizer 4CzIPN (0.002 mmol, 0.0016 g), nickel catalyst NiBr 2 ·diglyme nickel bromide (0.01 mmol, 0.0036 g), ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), reducing agent HEH diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (0.25 mmol, 0.0632 g), additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g) were successively added to a dry Schlenk tube. N,N'-dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL) was added via syringe. Then the Schlenk tube was removed from the glove box, and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. Then, under a nitrogen atmosphere, α-chloroborate (0.15 mmol, 0.0411 g) and (0.10 mmol, 0.0304 g) were added using a microsyringe. After addition, the Schlenk tube was closed again, and the reaction mixture was stirred and irradiated with blue light (λ = 450 - 455 nm) for 2 - 6 hours. Meanwhile, the temperature was controlled at 20 - 30 °C by a fan and air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous Na 2 SO 4 dried, filtered through diatomaceous earth, and concentrated in vacuo. It was separated by column chromatography to obtain 0.0279 g of the product with a yield of 67% and an ee value of 97%.

[0103] 1 1H NMR(600MHz,CDCl 3)δ8.04(d, J = 7.2 Hz, 2H), 7.55(t, J = 7.2 Hz, 1H), 7.43(t, J = 7.8 Hz, 2H), 4.31(t, J = 6.6 Hz, 2H), 3.97 - 3.90(m, 2H), 3.37 - 3.28(m, 2H), 1.84 - 1.71(m, 2H), 1.68 - 1.53(m, 2H), 1.51 - 1.37(m, 6H), 1.31 - 1.17(m, 15H), 1.15 - 1.06(m, 1H).

[0104] 13 C NMR(151 MHz, CDCl 3 )δ166.6, 132.8, 130.5, 129.5, 128.3, 82.9, 68.2, 65.0, 38.5, 34.3, 33.5, 33.1, 31.3, 29.0, 25.7, 24.8, 24.7.

[0105] HRMS: m / z(ESI) calculated [M + Na]+: 439.2626, found: 439.2627.

[0106] Example 10

[0107] Preparation:

[0108] In a glove box, to a dry Schlenk tube were successively added the photosensitizer 4CzIPN (0.002 mmol, 0.0016 g), the nickel catalyst NiBr 2 ·diglyme nickel bromide bis(diethylene glycol dimethyl ether) (0.01 mmol, 0.0036 g), the ligand L1 (0.020 mmol, 0.0062 g), sodium bicarbonate (0.25 mmol, 0.0210 g), the reducing agent HEH diethyl 2,6 - dimethyl - 1,4 - dihydropyridine - 3,5 - dicarboxylate (0.25 mmol, 0.0632 g), the additive magnesium trifluoromethanesulfonate (0.20 mmol, 0.0644 g). N,N’ - dimethylacetamide / trifluorotoluene (v / v = 1 / 1, 2 mL) was added via a syringe. Then the Schlenk tube was removed from the glove box, and degassed water (15 μL) was added under a nitrogen atmosphere. Subsequently, the reaction mixture was stirred at room temperature for 60 - 90 minutes. Then, under a nitrogen atmosphere, α - chloroborate (0.15 mmol, 0.0486 g) and (0.10 mmol, 0.0304 g). After addition, the Schlenk tube was closed again, and the reaction mixture was stirred and irradiated under blue light (λ = 450 - 455 nm) for 2 - 6 h. Meanwhile, the temperature was controlled at 20 - 30 °C by a fan and an air conditioner. After completion, the mixture was diluted with ethyl acetate and quenched with water. The aqueous solution was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered through diatomaceous earth, and concentrated in vacuo. It was separated by column chromatography to obtain 0.0196 g of the product The yield was 42% and the ee value was 83%.

[0109] 1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (d, J = 7.2 Hz, 2H), 7.53 (d, J = 7.2 Hz, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.35 - 7.24 (m, 5H), 4.49 (s, 2H), 4.30 (t, J = 6.0 Hz, 2H), 3.46 (d, J = 7.2 Hz, 2H), 1.82 - 1.71 (m, 2H), 1.69 - 1.58 (m, 2H), 1.54 - 1.35 (m, 6H), 1.21 (s, 12H), 1.07 - 0.95 (m, 1H).

[0110] 13 C NMR (101 MHz, CDCl 3 ) δ 166.7, 138.8, 132.7, 130.6, 128.3, 128.3, 127.6, 127.4, 82.9, 72.7, 70.7, 65.1, 31.0, 29.3, 29.0, 27.7, 25.7, 24.8.

[0111] HRMS: m / z (ESI) calculated [M + H] + : 467.2968, found: 467.2973.

[0112] Those skilled in the art should understand that those skilled in the art can achieve variations in combination with the prior art and the above embodiments, which will not be elaborated here. Such variations do not affect the essence of the present invention and will not be elaborated here.

[0113] The preferred embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the above specific embodiments, and the devices and structures not described in detail should be understood to be implemented in a common manner in the art; any person skilled in the art can make many possible changes and modifications to the technical solution of the present invention by using the methods and technical contents disclosed above, or modify it into an equivalent embodiment with equivalent changes, which does not affect the essence of the present invention. Therefore, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the technical solution of the present invention still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A preparation method of a chiral borate compound, characterized in that: The steps are as follows: (1) Under an inert gas atmosphere, a photosensitizer, a nickel catalyst, a chiral ligand, a base, a reducing agent, and an additive are added to water and an organic solvent and then reacted; The organic solvent is a mixed solvent of N,N'-dimethylacetamide and trifluorotoluene; The photosensitizer is 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile; The nickel catalyst is nickel bromide bis(ethylene glycol dimethyl ether); The chiral ligand is ligand (L1), and the structural formula of ligand (L1) is The base is sodium bicarbonate; The reducing agent is diethyl 2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate; The additive is magnesium trifluoromethanesulfonate; (2) Under an inert gas atmosphere, an α-chloroborate compound (I) and an alkyl iodide (II) are added to the above reaction solution, and reacted under blue light irradiation to obtain a chiral borate compound; The structural formula of the α-chloroborate compound (I) is as follows: The structural formula of the alkyl iodide (II) is as follows:

2. The preparation method according to claim 1, characterized in that, In step (1), the reaction temperature of the reaction is 0-150 °C, and the reaction time is 0.1-12 h; The photosensitizer is 1-100% molar equivalent of the alkyl iodide (II), the nickel catalyst is 1-100% molar equivalent of the alkyl iodide (II), the chiral ligand is 1-100% molar equivalent of the alkyl iodide (II), the base is 50-500% molar equivalent of the alkyl iodide (II), the reducing agent is 50-500% molar equivalent of the alkyl iodide (II), and the additive is 50-500% molar equivalent of the alkyl iodide (II); In step (2), the reaction temperature of the reaction is 0-150 °C, and the reaction time is 1-12 h; The dosage of the α-chloroborate (I) is 100-500% molar equivalent of the alkyl iodide (II).

3. The preparation method according to claim 2, characterized in that, In step (1), the reaction temperature of the reaction is 20-30 °C, and the reaction time is 60-90 min; The photosensitizer is 2% molar equivalent of the alkyl iodide (II), the nickel catalyst is 10% molar equivalent of the alkyl iodide (II), the chiral ligand is 20% molar equivalent of the alkyl iodide (II), the base is 250% molar equivalent of the alkyl iodide (II), the reducing agent is 250% molar equivalent of the alkyl iodide (II), and the additive is 200% molar equivalent of the alkyl iodide (II); In step (2), the reaction temperature of the reaction is 20-30 °C, and the reaction time is 2-6 h; The dosage of the α-chloroborate (I) is 150-200% molar equivalent of the alkyl iodide (II).

4. The preparation method according to claim 1, characterized in that, The power of the blue light is 30 W.

5. The preparation method according to claim 1, characterized in that, After the reaction in step (2) is completed, the product is washed, extracted, concentrated, and purified and separated.

Images