Method for olefin enantioselective carbon oxidation through photoelectricity and vanadium catalysis

Abstract

The invention discloses a method for olefin enantioselective carbon oxidation through photoelectric synergistic vanadium catalysis, and belongs to the technical field of photoelectric asymmetric catalysis. A bulk chemical organic solvent, an olefin substrate and an N-hydroxyimide substrate are used as raw materials, a vanadium catalyst, an electrolyte and a cathode hydrogen evolution reagent are added, and the enantiomerically enriched olefin carbon oxidation chiral product is prepared under the conditions of electrification and irradiation of an ultraviolet lamp. The method has the characteristics of simple and easily available raw materials, mild reaction conditions, simple and efficient reaction operation, simple and convenient reaction post-treatment, good functional group compatibility, large-scale preparation potential and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of photoelectric asymmetric catalysis, and particularly relates to a method for photoelectric synergistic vanadium catalytic enantioselective carbon oxidation of olefins. BACKGROUND

[0002] C(sp 3 )-H bond refers to a single bond formed by a carbon atom with an sp 3 hybridized orbital and a hydrogen atom, commonly found in alkanes (such as methane, ethane), alcohols, ethers, aliphatic compounds, etc. Such bonds are very common in bulk chemicals (such as petroleum, natural gas, basic organic raw materials). The bond dissociation energy of C(sp 3 )-H is relatively high, so it is difficult to be activated or functionalized (i.e., introducing other functional groups such as -OH, -Cl, -CN, etc.) under mild conditions. In contrast, some unsaturated bonds (such as C=C) or heteroatom bonds (such as O-H, N-H) are more easily broken or involved in reactions.

[0003] Direct high-value conversion of bulk chemical raw materials, especially direct functionalization of the ubiquitous C(sp 3 )-H bond in bulk chemicals, is a molecular construction method with high atom economy and step economy, and is also a long-term goal of academia and industry.

[0004] Taking some bulk chemicals as examples: the production of acetone in 2025 is expected to reach 83.4 million tons, pKa=26.5, C(sp 3 )-H bond dissociation energy 96 kcal / mol; the production of acetonitrile in 2025 is expected to reach 198,000 tons, pKa=31.3, C(sp 3 )-H bond dissociation energy 96 kcal / mol; the production of dichloromethane in 2025 is expected to reach 1.68 million tons, pKa=12.16, C(sp 3 )-H bond dissociation energy 95.7 kcal / mol. The above raw materials are often used as key solvents in laboratories and pharmaceutical / fine chemical industries: on the one hand, these compounds have relatively chemical inertness; on the other hand, the physical properties of these compounds affect the reaction rate, reactivity and selectivity of the chemical manufacturing process, which is often referred to as "solvent effect". However, a commonly overlooked fact is that such bulk chemicals contain the most basic chemical functional groups such as ketones, cyano groups and halogens, respectively. If a new type of catalytic system can be developed to directly convert inexpensive bulk chemicals as corresponding functional groups into higher value chiral compounds, it will undoubtedly be an extremely interesting and economically practical synthesis strategy.

[0005] Photoelectrochemistry combines electrocatalysis and photocatalysis, which can generate high-energy open-shell intermediates under mild redox potential conditions. However, the C(sp3 ) -H bond activation reagents such as chlorine radicals, tungstate salts, benzophenone, etc. will usually tend to activate the electron-rich C(sp 3 ) -H bond due to the polar matching effect, rather than the protonic C(sp 3 ) -H bond in molecules such as acetone, acetonitrile and dichloromethane. In addition, the radical species generated in situ after the activation of the C(sp 3 ) -H bond is further converted into an enantiomerically enriched molecule usually relies on another chiral metal catalyst. It is of high exploration value and challenging to use a single catalyst to achieve both processes (i.e. C(sp 3 ) -H bond activation process and asymmetric bond formation process) at the same time. The development of such a catalytic system is hindered because it is difficult to achieve two different mechanisms, two different processes from one catalyst. Therefore, it is necessary to develop a V catalyst that can achieve both the protonic C(sp 3 ) -H bond activation process (HAT) and catalyze the bimolecular radical homolytic substitution process to achieve chiral carbon-oxygen bond formation. SUMMARY

[0006] The present application discloses a photoelectric-driven vanadium-catalyzed enantiomeric conversion method of bulk chemicals, which uses a multi-functional vanadium electro-optical catalyst: can selectively activate the protonic C(sp 3 ) -H, is a highly efficient hydrogen atom transfer (HAT) catalyst; also can control the enantioselectivity of the reaction, is a chiral metal catalyst. The catalyst catalyzes the enantioselective three-component carbon oxidation reaction of olefins under photoelectric driving to realize the enantiomeric high-value conversion of bulk chemicals.

[0007] To achieve the above technical purposes, the present application provides a photoelectric synergistic vanadium-catalyzed enantioselective carbon oxidation method of olefins, which is carried out according to the following steps: (1) mixing an olefin substrate II, a vanadium catalyst, an N-hydroxy imide substrate III, an electrolyte and an organic solvent I to form a homogeneous reaction solution by adding a proton donor for cathodic hydrogen evolution reaction; (2) placing the reaction solution in an electrolytic cell provided with an anode and a cathode, irradiating with visible light with a wavelength of 365-420 nm at 0-25℃, and applying a constant current or a constant cell voltage to carry out electrolysis reaction, after the reaction is completed, the enantioselective olefin carbon oxidation product is obtained after separation and purification; Wherein, the vanadium catalyst is a chiral vanadium complex, the chiral ligand is selected from one of chiral bisphenol, chiral Schiff base, BINOL derivative, Salen type ligand or amino acid derivative ligand, and the catalytic radical substitution reaction; The N-hydroxyimide substrate III is an N-hydroxyimide compound having a general formula of R-N(OH)-C(O)Y, wherein R is an aromatic ring or an aliphatic chain, and Y is -C(O)- or -SO2-. The separation and purification is completed by silica gel column chromatography, preparative TLC or HPLC.

[0008] Further, the vanadium catalyst is a vanadium complex containing a pentavalent vanadium center V V =O, a chiral Schiff base ligand and one or more alkoxy or phenoxyl ligands.

[0009] Further, the vanadium catalyst is one of V-1 to V-6, and the specific structure includes: .

[0010] Further, the olefin substrate II is an olefin having a general formula of R 1 R 2 C=CR 3 H or R 1 R 2 C=CR 3 R 4 , wherein R 1 –R 4 is independently selected from one of hydrogen, C1–C 10 alkyl, C6–C 14 aryl, heteroaryl, ester, halogen substituent.

[0011] Further, the olefin substrate II is selected from one of: .

[0012] Further, the N-hydroxyimide substrate III is an N-hydroxyimide compound having a general formula of R-N(OH)-C(O)Y, wherein R is an aromatic ring or an aliphatic chain, and Y is -C(O)-.

[0013] Further, the N-hydroxyimide substrate III is selected from one of: .

[0014] Further, part of the carbon skeleton of the organic solvent I participates in the carbon oxidation reaction of the olefin and is introduced into the product; wherein the organic solvent I is selected from one of acetone, acetonitrile, dichloromethane, dibromomethane or 1,1-dichloroethane.

[0015] Further, the proton donor for hydrogen evolution reaction at the cathode to maintain charge balance is selected from one of carboxylic acids, alcohols or phenolic compounds, preferably one of acetic acid, trifluoroacetic acid, benzoic acid, p-nitrophenol, hexafluoroisopropanol, trifluoroethanol or difluoroethanol, and more preferably acetic acid.

[0016] Further, the electrolyte is a supporting electrolyte for improving the ionic conductivity of the reaction system and maintaining electrochemical stability. The electrolyte is selected from quaternary ammonium salts, quaternary phosphonium salts or lithium salts, with non-coordinating and oxidation-resistant anions, selected from one of BF4 - , PF6 - , CIO4 - , OTf - or NTf2 - ; Preferably, the electrolyte is one of tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium perchlorate or lithium perchlorate, and more preferably tetrabutylammonium tetrafluoroborate.

[0017] Further, the product IV is selected from: .

[0018] Further, the anode electrode material is a chemically stable conductive material, selected from one of noble metals, carbon-based materials or corrosion-resistant metal alloys; wherein the noble metal is platinum or gold; the carbon-based material is carbon rod, carbon cloth, carbon felt, reticulated vitreous carbon RVC or graphite; the corrosion-resistant metal alloy is stainless steel or nickel-based alloy, and preferably carbon felt.

[0019] Further, the cathode electrode material is one of platinum, nickel, carbon cloth, carbon felt, RVC or carbon rod electrode material.

[0020] Further, the cathode has the ability to promote hydrogen evolution reaction for charge compensation, preferably platinum.

[0021] Further, the electrolysis reaction is carried out in constant current or constant voltage mode, When constant current electrolysis is used, the current is 1 ~ 20mA, preferably 1 ~ 6mA corresponding to a current density of 4.4 A / m 2 ~ 22.6 A / m 2 , and the electrolysis time is 13 ~ 19h; When constant voltage electrolysis is used, the applied cell voltage is 1.2 ~ 2.0 V, preferably 1.4 ~ 1.8 V; and the electrolysis time is 19 ~ 21h.

[0022] Advantages of the present application Compared with the prior art, the present application discloses a photoelectric-driven enantioselective carbon oxidation method of bulk chemicals and olefins catalyzed by vanadium. The present application has the advantages of simple and readily available reaction raw materials, mild reaction conditions, wide substrate universality, high reaction efficiency, large-scale preparation potential, high yield of target product, simple reaction operation and post-processing process, etc. For example, under laboratory conditions, only simple column chromatography separation method is needed to purify the hydrogenation product with a mixture of petroleum ether and ethyl acetate as the eluent to obtain pure hydrogenation product. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 Chemical structural formula of the vanadium catalyst V-1 ~ V-6 described in the present application.

[0024] Figure 2 NMR spectrum of the product of Example 1.

[0025] Figure 3 NMR spectrum of the product of Example 2.

[0026] Figure 4 NMR spectrum of the product of Example 3.

[0027] Figure 5 NMR spectrum of the product of Example 4.

[0028] Figure 6 NMR spectrum of the product of Example 5.

[0029] Figure 7 NMR spectrum of the product of Example 6.

[0030] Figure 8 Principle diagram of the vanadium catalytic reaction of the present application.

[0031] Figure 9 Yield and ee value statistics diagram of the corresponding olefin carbon oxidation product prepared by the present application using different types of substrates.

[0032] Figure 10 Yield and ee value statistics diagram of the corresponding olefin carbon oxidation product prepared by the present application using different types of substrates. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical scheme and advantages of the present application clearer and more apparent, the following embodiments will be further described in detail. The specific embodiments described herein are only used to explain the present application and do not limit the present application.

[0034] Example 1 (1) Add vanadium catalyst V-1 to the dried reaction tube. (5.0 mol%, 8.6 mg), N-hydroxyphthalimide (NHPI, (0.3 mmol, 48.9 mg), Tetrabutyltetrafluoroborate ( n Bu4NBF4, (0.05 M, 98.8 mg), and inserted the carbon felt anode (GF(+)) and platinum cathode (Pt(-)) into the above reaction tube, sealed the reaction system, purged three times with inert gas (Ar), and injected 3-buten-1-yn-1-ylbenzene into the above reaction tube using a syringe. (0.45 mmol, 60 μL), acetone (6.0 mL), HOAc acetic acid (6.0 mmol, 343 μL).

[0035] In this step, the vanadium catalyst, acting as a HAT catalyst, can capture H atoms from solvent molecules (acetone) under photoexcitation to generate carbon radicals. These radicals then add to olefins to obtain new radical intermediates. The pentavalent vanadium catalyst can catalyze the bimolecular homolytic substitution process of these radical intermediates with NHPI compounds to obtain the target product. n Bu4NBF4 improves the conductivity of the solution and stabilizes the current, and BF4 - Inert and unlikely to participate in side reactions; the carbon felt anode serves as the oxidation site, providing an electron outlet for the direct oxidation of vanadium catalyst; the platinum cathode serves as the reduction site, undergoing proton reduction to generate H2, or O2 reduction (if trace oxygen is present), maintaining charge balance; acetone, in addition to being a solvent, also acts as a reaction substrate; 3-buten-1-yn-1-ylbenzene, containing an olefin, serves as a substrate, accepting free radical addition and participating in subsequent reactions; acetic acid (AcOH) acts as a buffer, proton source, and deprotonation regulator, reacting with AcO... - Forming a buffer system to regulate NHP NHPI - balance.

[0036] (2) At room temperature, using 1.6V constant voltage electrolysis, under the irradiation of 10W power 390nm wavelength LED lamp for 19h, the vanadium catalyst has obvious ultraviolet absorption signal near 390nm, after the vanadium is excited, it can capture the hydrogen on the acetone and participate in the subsequent reaction. After the reaction is completed, the solvent is removed on the rotary evaporator, and then separated by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 6) to obtain 75.1mg of light yellow oily liquid product: (R)-2-((6-oxo-1-phenylhept-1-yn-3-yl)oxy)isoindoline-1,3-dione in 72% separation yield (calculated yield based on the amount of NHPI: 0.3mmol as the reaction equivalent) and 90% ee; = 125.8 (c = 0.1, CH2Cl2).

[0037] The reaction formula is as follows: HPLC detection uses Chiralpak AS-H chromatographic column, the mobile phase is n-hexane: isopropanol (volume ratio is 95:5), the flow rate is 0.5 mL / min, the temperature is 30°C, and the detection wavelength is 254 nm. The retention time of the product is t R = 24.0 min (major), 26.3 min (minor), based on the HPLC-determined ee value, the RS configuration of the same molecule is separated into two absorption peaks on HPLC, and the ratio of the peak areas is equal to the mass ratio of the two configuration substances.

[0038] NMR data of the product: 1 H NMR (600 MHz, Chloroform-d) δ [ppm] = 7.86 - 7.81 (m, 2H), 7.76 - 7.72 (m, 2H), 7.38 - 7.33 (m, 2H), 7.31 - 7.25 (m, 3H), 5.31 (dd, J = 6.7, 5.2 Hz, 1H), 3.04 - 2.96 (m, 1H), 2.92 - 2.84 (m, 1H), 2.37 - 2.30 (m, 2H), 2.25 (s, 3H). 13 C NMR (151 MHz, Chloroform-d) δ [ppm] = 207.6, 163.7, 134.6, 131.7, 128.9, 128.3, 123.6, 121.8, 89.0, 84.5, 77.2, 38.5, 30.3, 27.9. The NMR spectrum of the product is shown in Figure 2

[0039] HRMS (ESI) m / z calculated for [M+H] + : 348.1230, found: 348.1242.

[0040] Example 2 (1) In a dry treated reaction tube, vanadium catalyst V-1 (5.0 mol%, 8.6 mg), N-hydroxyphthalimide (0.3 mmol, 48.9 mg), tetrabutylammonium tetrafluoroborate (0.05 M, 98.8 mg) were added, and carbon felt anode, metal platinum cathode were inserted into the above reaction tube, the reaction system was sealed, replaced with inert gas (Ar) for three times, 3-butyn-1-ylbenzene (0.6 mmol, 80 μL), acetonitrile (6.0 mL), acetic acid (6.0 mmol, 343 μL) were injected into the above reaction tube using a syringe This step uses acetonitrile as a solvent and a source of cyanomethyl (•CH2CN); NHPI provides N–O radical precursors; vanadium catalyst V-1 enables enantiocontrol; light plus constant voltage electrolysis synergistically promotes electron transfer.

[0041] (2) Electrolysis was carried out at room temperature using a constant voltage of 1.6 V, and the reaction was carried out under irradiation of a LED lamp with a power of 10 W and a wavelength of 390 nm for 21 h. After the reaction was completed, the solvent was removed on a rotary evaporator, and then separated by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 5) to obtain 66.9 mg of the product (R)-4-((1,3-dioxoisoindolin-2-yl)oxy)-6-phenylhex-5-ynenitrile in the form of a colorless oily liquid with a separation yield of 67% (calculated yield based on the amount of NHPI: 0.3 mmol) and 92% ee; = 138.4 (c = 0.1, CH2Cl2).

[0042] The reaction scheme is as follows: HPLC detection used a Chiralpak AS-H chromatographic column, the mobile phase was n-hexane: isopropanol (volume ratio 80:20), the flow rate was 1.0 mL / min, the temperature was 30°C, the detection wavelength was 254 nm, and the retention time t R = 22.5 min (major), 26.0 min (minor).

[0043] NMR data of the product:​1 ¹H NMR (600 MHz, Chloroform-d) δ [ppm] = 7.86 - 7.84 (m, 2H), 7.77 - 7.75 (m, 2H), 7.37 - 7.36 (m, 2H), 7.33 - 7.32 (m, 1H), 7.30-7.27 (m, 2H), 5.38 - 5.36 (m, 1H), 2.94 - 2.81 (m, 2H), 2.43 - 2.39 (m, 2H), with NHPI group (4H), alkynyl benzene ring (5H), α-alkyl group (1H), and two methylene groups (4H).

[0044] 13 C NMR (151 MHz, Chloroform-d) δ [ppm] = 163.6, 134.8, 131.8, 129.3,128.8, 128.4, 123.8, 121.2, 119.0, 90.3, 82.7, 76.1, 30.0, 13.2. The NMR spectrum of the product is as follows Figure 3 As shown.

[0045] High-resolution mass spectrometry data of the product: HRMS (ESI) m / z calculated for [M+H] + : 331.1090, found: 331.1077.

[0046] Example 3 (1) In a dried reaction tube, add vanadium catalyst V-1 (5.0 mol%, 8.6 mg), N-hydroxy-o-phthalimide (0.3 mmol, 48.9 mg), and tetrabutylammonium tetrafluoroborate (0.1 M, 197.6 mg). Insert the carbon felt anode and platinum cathode into the reaction tube, seal the reaction system, and purge it three times with an inert gas (Ar). Then, inject 3-buten-1-yn-1-ylbenzene (0.6 mmol, 80 μL), dichloromethane (DCM, 6.0 mL), dimethyl sulfoxide (DMSO, 0.3 mL), and acetic acid (6.0 mmol, 343 μL) into the reaction tube using a syringe.

[0047] In this step, DCM as the main solvent: solubility of organic substrate; DMSO has strong polarity (ε = 47), improve the dielectric constant, conducive to ion pair separation, and help to dissolve large polar compounds and salts, improve the conductivity. Among them is the addition of DCM to the olefin after being hydrogenated by vanadium, the free radicals produced after the addition of the olefin, under vanadium catalysis, undergo asymmetric radical substitution with NHPI to obtain the product in the equation.

[0048] (2) At room temperature, using 3 mA constant current electrolysis, under the power of 10 W, wavelength 390 nm LED light irradiation reaction for 13 h. After the reaction was completed, the solvent was removed by rotary evaporator, then separated by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 10), with 68 % separation yield (calculated yield based on the amount of NHPI: 0.3 mmol as the reaction equivalent), 89 % ee to obtain 75.9 mg of colorless oily liquid product: (R)-2-((5,5-dichloro-1-phenylpent-1-yn-3-yl)oxy)isoindoline-1,3-dione; = 129.7 (c = 0.1, CH2Cl2).

[0049] The reaction formula is as follows: HPLC detection uses Chiralpak AS-H chromatographic column, the mobile phase is n-hexane: isopropanol (volume ratio is 90:10), the flow rate is 0.5 mL / min, the temperature is 30 ℃, the detection wavelength is 254 nm, the retention time tR = 18.5 min (major), 19.7 min (minor).

[0050] NMR data of the product: 1 H NMR (600 MHz, Chloroform-d) δ [ppm] = 7.87 - 7.85(m, 2H), 7.77 - 7.75 (m, 2H), 7.39 - 7.37 (m, 2H), 7.33 – 7.26 (m, 3H), 6.23(dd, J = 8.3, 5.0 Hz, 1H), 5.44 (dd, J = 8.9, 4.7 Hz, 1H), 3.11 - 3.04 (m,1H), 2.85 - 2.78 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ [ppm] = 163.7, 134.8, 131.9, 129.3,128.9, 128.5, 123.9, 121.3, 90.0, 82.9, 75.1, 69.1, 48.0. The NMR spectrum of the product is shown in Figure 4

[0051] High resolution mass spectrometry data of the product: HRMS (ESI) m / z calculated for [M+H]+: 374.0345, found: 374.0334. Example 4 (1) In a dry treated reaction tube, vanadium complex V-1 (5.0 mol%, 8.6 mg), N-hydroxyphthalimide (0.3 mmol, 48.9 mg), tetrabutylammonium tetrafluoroborate (0.1 M, 197.6 mg) were added, carbon felt anode, platinum metal cathode were inserted into the above reaction tube, the reaction system was sealed, replaced with inert gas (Ar) for three times, 3-butyn-1-ylbenzene (0.6 mmol, 80 μί), 1,2-dichloroethane (DCE, 6.0 mL), dimethyl sulfoxide (DMSO, 0.3 mL), acetic acid (6.0 mmol, 343 μί) were injected into the above reaction tube using a syringe.

[0052] In this step, DCE acts as a polar aprotic solvent on one hand to dissolve salts and organic compounds, on the other hand, as a reaction substrate to provide carbon radical precursor; DMSO mainly can increase the dielectric constant and help to dissolve large polarity and salt compounds.

[0053] (2) At room temperature, electrolysis was carried out using a constant current of 1.5 mA, under the irradiation of a LED lamp with a power of 10 W and a wavelength of 390 nm for 21 h. After the reaction was completed, the solvent was removed by a rotary evaporator, then separated by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 10) to obtain 70.3 mg of colorless oily liquid product: 2-(((3R)-5,6-dichloro-1-phenylhex-1-yn-3-yl)oxy)isoindoline-1,3-dione; in 60% separation yield (calculated yield based on the amount of NHPI: 0.3 mmol as the reaction equivalent), 90% ee / 90% ee, 1:1 d.r. = 130.6 (c = 0.11, CH2Cl2).

[0054] The reaction scheme is as follows:​ HPLC detection using Chiralpak OD-H column with mobile phase of n-hexane: isopropanol (volume ratio 97:3) at a flow rate of 0.5 mL / min, temperature of 30 °C, and detection wavelength of 254 nm, retention time t R = 31.6 min (major), 33.1 min (minor); t R = 36.2 min (major), 40.5 min (minor).

[0055] NMR data of the product: 1 H NMR (600 MHz, Chloroform-d) δ [ppm] = 7.87 - 7.84 (m, 2H), 7.78 - 7.75 (m, 2H), 7.39 - 7.36 (m, 1H), 7.33 - 7.26 (m, 5H), 5.53 - 5.47 (m, 1H), 4.81 - 4.75 (m, 0.49H), 4.50 - 4.44 (m, 0.49H), 4.07 - 4.03 (m, 0.50H), 3.95 - 3.90 (m, 1H), 3.87 - 3.82 (m, 0.48H), 2.84 - 2.77 (m, 0.51H), 2.74 - 2.61 (m, 0.5H), 2.65 - 2.57 (m, 0.47H), 2.38 - 2.31 (m, 0.48H). 13 C NMR (151 MHz, Chloroform-d) δ [ppm] = 163.7, 163.6, 134.7, 134.6, 131.8, 131.7, 129.1, 129.0, 128.84, 128.80, 128.34, 128.32, 123.72, 123.69, 121.5, 121.3, 90.0, 89.2, 84.0, 83.2, 77.3, 77.0, 76.8, 75.7, 75.0, 56.9, 56.7, 48.7, 48.2, 40.9, 39.2. NMR spectrum of the product is shown in Figure 5 .

[0056] High resolution mass spectrometry data of the product: HRMS (ESI) m / z calculated for [M+H] +: 388.0502, found: 388.0488. Example 5 (1) In a dried reaction tube, vanadium complex V-1 (5.0 mol%, 8.6 mg), N-hydroxyphthalimide (0.3 mmol, 48.9 mg), tetrabutylammonium tetrafluoroborate (0.1 M, 197.6 mg) were added, and carbon felt anode, metallic platinum cathode were inserted into the reaction tube, the reaction system was sealed, replaced with inert gas (Ar) for three times, 3-butyn-1-ylbenzene (0.6 mmol, 80 μL), dibromomethane (CH2Br2, 5.0 mL), dimethyl sulfoxide (DMSO, 0.3 mL), acetone (3.5 mL), acetic acid (6 mmol, 343 μL) were injected into the reaction tube using a syringe.

[0057] In this step, CH2Br2 acts as a polar solvent to dissolve salts and organic compounds, and also generates carbon radical (•CHBr2) precursor by hydrogen abstraction from the excited vanadium catalyst; DMSO and acetone act as polar solvents to help dissolve large polar compounds and salts. (2) At room temperature, electrolysis was carried out using a constant current of 1.5 mA, and the reaction was carried out under irradiation of a LED lamp with a power of 10 W and a wavelength of 390 nm for 19 h. After the reaction was completed, the solvent was removed by a rotary evaporator, and then the product was separated by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 10) in a separation yield of 57 % (calculated yield based on the amount of NHPI: 0.3 mmol as the reaction equivalent), 90 % ee to obtain 79.5 mg of colorless oily liquid product: (R)-2-((5,5-dibromo-1-phenylpent-1-yn-3-yl)oxy)isoindoline-1,3-dion; = 122.7 (c = 0.11, CH2Cl2).

[0058] The reaction scheme is HPLC detection used a Chiralpak AS-H chromatographic column, the mobile phase was n-hexane: isopropanol (volume ratio 85:15), the flow rate was 0.5 mL / min, the temperature was 30°C, and the detection wavelength was 254 nm, the retention time t R = 17.9 min (major), 19.2 min (minor).

[0059] NMR data of the product: 1H NMR (600 MHz, Chloroform-d) δ [ppm] = 7.87 - 7.85(m, 2H), 7.78 - 7.75 (m, 2H), 7.39 - 7.37 (m, 2H), 7.34 - 7.33 (m, 1H), 7.30- 7.27 (m, 2H), 6.11 (dd, J = 8.7, 5.2 Hz, 1H), 5.42 (dd, J = 8.9, 4.7 Hz, 1H), 3.30 - 3.25 (m, 1H), 3.04 - 2.99 (m, 1H). 13 C NMR (151 MHz, Chloroform-d) δ [ppm] = 163.8, 134.8, 131.9, 129.3,128.9, 128.5, 123.9, 121.4, 90.1, 82.8, 76.4, 49.6, 39.6. The NMR spectrum of the product is as follows Figure 6 As shown.

[0060] High-resolution mass spectrometry (HRMS) (ESI) data m / z calculated for [M+H] + : 461.9335, found:461.9317.

[0061] Example 6 (1) Add vanadium complex V-6 to a reaction tube that has been dried. (10.0 mol%, 6.3 mg), 4-methyl-N-hydroxyphthalimide (Me-NHPI, 0.2 mmol, 35.4 mg), and tetrabutylammonium tetrafluoroborate (0.1 M, 196 mg) were added to the reaction tube. The carbon felt anode and the platinum cathode were inserted into the reaction tube, the reaction system was sealed, and the system was purged three times with an inert gas (Ar). 4-Bistyrene (0.3 mmol, 54.0 mg), acetone (6.0 mL), and acetic acid (6.0 mmol, 343 μL) were injected into the reaction tube using a syringe.

[0062] In this step, the vanadium complex acts as a HAT catalyst. Upon photoexcitation, it can abstract the α-H group of acetone to generate a •CH2COCH3 radical. The •CH2COCH3 radical then adds to 4-bistyrene, producing a new radical intermediate. The vanadium complex also acts as a chiral catalyst, catalyzing the asymmetric radical substitution reaction of this intermediate with NHPI to generate the product.

[0063] (2) at 0 °C, using a constant voltage of 1.6 V, electrolysis for 13 h under irradiation of a LED lamp at a power of 10 W and a wavelength of 395 nm. After the reaction was completed, the solvent was removed by a rotary evaporator and then separated by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 8) to give 39.0 mg of the product as a colorless oily liquid in 47% isolated yield (calculated yield based on the amount of Me-NHPI: 0.2 mmol as a reaction equivalent), 89% ee: (S)-2-((1-([1,1'-biphenyl]-4-yl)-4-oxopentyl)oxy)-5-methylisoindoline-1,3-dione; = -219.0 (c = 0.09, CH2Cl2).

[0064] The reaction scheme is as follows: HPLC detection used a Chiralpak AS-H column with a mobile phase of n-hexane: isopropanol (volume ratio of 80:20) at a flow rate of 1.0 mL / min, a temperature of 30 °C, and a detection wavelength of 254 nm, with retention times of t R = 17.1 min (major), 22.6 min (minor).

[0065] NMR data of the product: 1 H NMR (600 MHz, Chloroform-d) δ [ppm] = 7.60 (d, J =7.6 Hz, 1H), 7.58 - 7.51 (m, 7H), 7.45 (d, J = 7.7 Hz, 1H), 7.41 (t, J = 7.4Hz, 2H), 7.32 (t, J = 7.8 Hz, 1H), 5.35 - 5.33 (m, 1H), 2.90 - 2.84 (m, 1H),2.74 - 2.65 (m, 1H), 2.44 (s, 3H), 2.39 - 2.33 (m, 1H), 2.25 - 2.20 (m, 4H).

[0066] 13C NMR (151 MHz, Chloroform-d) δ [ppm] = 207.9, 164.0, 163.98, 145.8, 141.7, 140.6, 137.2, 134.9, 129.2, 128.9, 128.2, 127.5, 127.2, 127.1, 126.2, 124.1, 123.5, 88.1, 39.5, 30.3, 29.3, 22.2.

[0067] HRMS (ESI) m / z calculated for C 26 H 23 O4NNa [M+Na] + : 436.1519, found: 436.1510.

[0068] The NMR spectra of the product are shown in Figure 7

[0069] Example 7 (1) In a dry treated reaction tube, vanadium catalyst V-1 (5.0 mol%, 103 mg), N-hydroxyphthalimide (4.0 mmol, 652 mg), tetrabutylammonium tetrafluoroborate (0.05 M, 1.5 g) were added, and a graphite felt anode and a metallic platinum cathode were inserted into the reaction tube, which was sealed, purged three times with inert gas (Ar), and 3-butyn-1-ylbenzene (6 mmol, 810 μL), acetone (90 mL), acetic acid (80 mmol, 4.4 mL) were injected into the reaction tube using a syringe.

[0070] (2) The reaction solution was electrolyzed using a constant current of 15 mA while ensuring that the reaction solution was at room temperature, and the reaction was carried out for 30 h under irradiation with a LED lamp with a power of 50 W and a wavelength of 390 nm. After the reaction was completed, the solvent was removed on a rotary evaporator, and the product was isolated by silica gel column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 6) in a separation yield of 68% (calculated yield based on the amount of NHPI: 4 mmol as a reaction equivalent) and 91% ee to give 0.97 g of the product as a light yellow oily liquid: (R)-2-((6-oxo-1-phenylhept-1-yn-3-yl)oxy)isoindoline-1,3-dione; = 125.8 (c = 0.1, CH2Cl2).

[0071] ​HPLC detection used a Chiralpak AS-H column with a mobile phase of n-hexane: isopropanol (95:5 by volume) at a flow rate of 0.5 mL / min, a temperature of 30 °C, and a detection wavelength of 254 nm. The retention times t R = 24.0 min (major), 26.3 min (minor).

[0072] Comparative Example 1: No light, otherwise same conditions as Example 1.

[0073] No product from Example 1 was detected without light.

[0074] Comparative Example 2: No electricity, otherwise same conditions as Example 1.

[0075] Trace amounts of product were detected without electricity, due to the fact that the 5% equivalent of vanadium catalyst, upon light, can grab the hydrogen atoms from the solvent and mediate the radical substitution of NHPI, but because there is no electricity, the vanadium catalyst cannot recycle, thus very small amounts of product (<5%) were generated.

[0076] Comparative Example 3: No vanadium catalyst, otherwise same conditions as Example 1.

[0077] No product from Example 1 was detected without vanadium catalyst.

[0078] Comparative Example 4: No NHPI, gas atmosphere changed from Ar to air, otherwise same conditions as Example 1.

[0079] After the reaction was complete, product 1 was obtained in 14% isolated yield: and product 2 was obtained in 20% isolated yield: indicating that the reaction can generate the desired radical precursor without NHPI.

[0080] Characterization data for product 1 and product 2 are as follows: Product 1 1 H NMR (600 MHz, Chloroform-d) δ 7.56 (d, J = 7.6 Hz, 2H), 7.45 (t, J= 7.4 Hz, 1H), 7.37 (t, J = 7.6 Hz, 2H), 2.98 (t, J = 6.2 Hz, 2H), 2.82 (t, J= 6.3 Hz, 2H), 2.21 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 206.4, 186.0, 133.1, 130.9, 128.7, 120.0, 91.2, 87.6, 39.2, 36.9, 30.0. HRMS (ESI) m / z calculated for C 13 H 13 O2 [M+H] + : 201.0910, found:201.0915. Product 2 1 H NMR (600 MHz, Chloroform-d) δ 7.44 - 7.40 (m, 2H), 7.31 - 7.26 (m, 3H), 4.68 (t, J = 6.1 Hz, 1H), 2.81 - 2.70 (m, 2H), 2.51 (br, 1H), 2.20 (s, 3H), 2.11 - 2.07 (m, 2H). 13 C NMR (151 MHz, Chloroform-d) δ 209.1, 131.8, 128.7, 128.4, 122.5, 89.4, 85.4, 62.2, 39.4, 31.5, 30.2. HRMS (ESI m / z) calculated for C 13 H 13 O [M-OH] + : 185.0961, found:186.0966. Comparative Example 5: In a reaction tube under argon atmosphere, 0.1 mmol vanadium complex V-1 (calculated yield with vanadium complex amount: 0.1 mmol as reaction equivalent) was added, 0.3 mmol TEMPO was added: , under the irradiation of LED lamp with wavelength 390 nm and power 10 W, reaction at room temperature for 6 h; in addition, control experiments without light and without vanadium complex were carried out, and the following results were obtained. It is shown that the vanadium complex in the present application can capture hydrogen atoms in the solvent acetone under light excitation.

[0081] The characterization data of product 1a are as follows: 1H NMR (600 MHz, Chloroform-d) δ 4.37 (s, 2 H), 2.20 (s, 3 H), 1.58 -1.52 (m, 1H), 1.46 - 1.42 (m, 4H), 1.34 - 1.31 (m, 1H), 1.14 (d, J = 12.0 Hz,12H). 13 C NMR (151 MHz, Chloroform-d) δ 207.2, 83.4, 60.2, 39.7, 33.0, 27.4,20.3, 17.1. HRMS (ESI) calcd for C 12 H 24 O2N, [M+H]+: 214.18016, found: 214.17941. Figure 8 This reflects the catalytic mechanism in the above embodiments. After photoexcitation, the vanadium catalyst can seize protonated C(sp3)-H bonds in solvent molecules, generating free radical I and a tetravalent vanadium species. This free radical adds to the olefin feedstock to give free radical intermediate II. This intermediate participates in the V-catalyzed bimolecular homolytic substitution process, forming a bond with NHPI to give product III, while simultaneously generating one molecule of tetravalent vanadium. The tetravalent vanadium is then anolyzed and regenerated into pentavalent vanadium, completing the catalytic cycle. The hydrogen evolution reagent added to the reaction is reduced at the cathode to release hydrogen gas, ensuring charge conservation in the reaction.

[0082] The above embodiments illustrate the reaction process of representative substrates of the present invention. To demonstrate the substrate applicability of this method in terms of yield and enantioselectivity, this embodiment further expands the types of substrates based on the above embodiments, using the same method to prepare corresponding olefin carbon oxidation products. The olefin substrates are selected from: One of them; N-hydroxyimide substrate III is selected from: One of them; Product IV Selected from: One of them, and its yield and ee value are calculated. The statistical results are as follows: Figure 9 and Figure 10 As shown.

[0083] Combination Figure 9 and Figure 10The expanded reaction substrate types and yield results can show that the reaction substrates of the application have wide universality, and the target product has high yield and high enantioselectivity. The reaction of the application has good functional group compatibility and wide substrate range, and through photoelectric driving, the reaction condition is mild, the reaction operation is simple, efficient, has the potential of scale-up production, and has wide application prospect.

[0084] The above describes the preferred embodiments of the application in detail. The ordinary researchers in the art can obtain similar technical solutions without creative labor on the basis of the application. Therefore, the technical solutions obtained through simple logical divergence or limited modification on the basis of the application should be within the protection scope determined by the claims.

Claims

1. A method for photoelectric synergistic vanadium-catalyzed enantioselective carbon oxidation of olefins, characterized in that, The reaction proceeds according to the following steps: (1) Mix olefin substrate II, vanadium catalyst, N-hydroxyimide substrate III, electrolyte and organic solvent I, and add proton donor for the cathode hydrogen evolution reaction to form a homogeneous reaction solution; (2) The reaction solution is placed in an electrolytic cell equipped with an anode and a cathode, and irradiated with visible light with a wavelength of 365-420 nm at 0-25°C. A constant current or constant cell voltage is applied to carry out the electrolytic reaction. After the reaction is completed, the enantioselective olefin carbon oxidation product is obtained by separation and purification. The vanadium catalyst is a chiral vanadium complex, and the chiral ligand is selected from one of chiral bisphenols, chiral Schiff bases, BINOL derivatives, Salen-type ligands or amino acid-derived ligands, catalyzing free radical substitution reactions; The N-hydroxyimide substrate III is an N-hydroxyimide compound having the general formula R–N(OH)–C(O)Y, wherein R is an aromatic ring or an aliphatic chain, and Y is –C(O)– or –SO2–. The separation and purification were performed using silica gel column chromatography, preparative TLC, or HPLC.

2. The method according to claim 1, characterized in that, The vanadium catalyst described is a vanadium catalyst containing a pentavalent vanadium center (V). V =Vanadium complexes consisting of O, a chiral Schiff base ligand, and one or more alkoxy or phenoxy ligands.

3. The method according to claim 1, characterized in that, The olefin substrate II has the general formula R. 1 R 2 C=CR 3 H or R 1 R 2 C=CR 3 R 4 The olefin shown, wherein R 1 –R 4 Independently selected from hydrogen, C1–C 10 Alkyl, C6–C 14 One of aryl, heteroaryl, ester, or halogen substituents.

4. The method according to claim 1, characterized in that, The N-hydroxyimide substrate III is an N-hydroxyimide compound having the general formula R–N(OH)–C(O)Y, where R is an aromatic ring or aliphatic chain and Y is –C(O)–.

5. The method according to claim 1, characterized in that, The carbon skeleton of organic solvent I participates in the carbon oxidation reaction of olefins and is introduced into the product; Wherein, the organic solvent I is selected from any one of acetone, acetonitrile, dichloromethane, dibromomethane, 1,2-dichloroethane, or 1,2-dibromoethane.

6. The method according to claim 1, characterized in that, The proton donor is used to maintain charge balance by initiating a hydrogen evolution reaction at the cathode, and is selected from one of carboxylic acids, alcohols, or phenolic compounds, preferably one of acetic acid, trifluoroacetic acid, benzoic acid, p-nitrophenol, hexafluoroisopropanol, trifluoroethanol, or difluoroethanol.

7. The method according to claim 1, characterized in that, The electrolyte is a supporting electrolyte, used to improve the ionic conductivity of the reaction system and maintain electrochemical stability; The electrolyte is selected from quaternary ammonium salts, quaternary phosphorus salts, or lithium salts, and its anion is a non-coordinated and antioxidant anion selected from BF4. - PF6 - ClO4 - OTf - or NTf2 - One of the following; preferably one of tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium perchlorate, or lithium perchlorate.

8. The method according to claim 1, characterized in that, The anode electrode material is a chemically stable conductive material selected from one of noble metals, carbon-based materials, or corrosion-resistant metal alloys; wherein the noble metal is platinum or gold; the carbon-based material is carbon rod, carbon cloth, carbon felt, reticulated glassy carbon (RVC), or graphite; and the corrosion-resistant metal alloy is stainless steel or a nickel-based alloy.

9. The method according to claim 1, characterized in that, The cathode electrode material is one of platinum, nickel, carbon cloth, carbon felt, RVC, or carbon rod electrode materials; preferably, the cathode has the ability to promote the hydrogen evolution reaction and is used to achieve charge compensation.

10. The method according to claim 1, characterized in that, The electrolysis reaction is carried out in a constant current or constant voltage mode. When constant current electrolysis is used, the current is 1~20mA, preferably 1~6mA, corresponding to a current density of 4.4 A / m. 2 ~26.6A / m 2 The electrolysis time is 13~19h; When constant voltage electrolysis is used, the applied cell voltage is 1.2~2.0 V, preferably 1.4~1.8 V; the electrolysis time is 19~21 h.

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