CN115814849A - Synthetic catalyst and catalytic method for various tri-substituted olefin compounds and heterocyclic compounds - Google Patents
Synthetic catalyst and catalytic method for various tri-substituted olefin compounds and heterocyclic compounds Download PDFInfo
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- 239000003054 catalyst Substances 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 30
- 150000002391 heterocyclic compounds Chemical class 0.000 title claims abstract description 18
- -1 olefin compounds Chemical class 0.000 title claims abstract description 18
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 230000003197 catalytic effect Effects 0.000 title claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 192
- 238000007342 radical addition reaction Methods 0.000 claims abstract description 6
- 150000003254 radicals Chemical class 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 150000001336 alkenes Chemical class 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000002887 hydroxy group Chemical class [H]O* 0.000 claims description 4
- 239000012298 atmosphere Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 48
- 238000006243 chemical reaction Methods 0.000 abstract description 24
- 238000001308 synthesis method Methods 0.000 abstract description 7
- 239000011941 photocatalyst Substances 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 230000015572 biosynthetic process Effects 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- 238000005481 NMR spectroscopy Methods 0.000 description 41
- 230000005526 G1 to G0 transition Effects 0.000 description 22
- 239000003208 petroleum Substances 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 238000010200 validation analysis Methods 0.000 description 21
- 238000012795 verification Methods 0.000 description 21
- 238000010898 silica gel chromatography Methods 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- 238000004821 distillation Methods 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- 239000012230 colorless oil Substances 0.000 description 14
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000005292 vacuum distillation Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 5
- 101001053395 Arabidopsis thaliana Acid beta-fructofuranosidase 4, vacuolar Proteins 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 101001053401 Arabidopsis thaliana Acid beta-fructofuranosidase 3, vacuolar Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000013375 chromatographic separation Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 101100132433 Arabidopsis thaliana VIII-1 gene Proteins 0.000 description 1
- 101100459319 Arabidopsis thaliana VIII-2 gene Proteins 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000004966 cyanoalkyl group Chemical group 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000007539 photo-oxidation reaction Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
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- Y02P20/584—Recycling of catalysts
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Abstract
The invention belongs to the field of organic synthesis, and discloses a synthetic catalyst and a catalytic method of various tri-substituted olefin compounds and heterocyclic compounds, which comprises the following steps: under the irradiation of blue light, the compound shown in the formula VII, the compound shown in the formula VIII, the compound shown in the formula IX, the compound shown in the formula X, the compound shown in the formula XI or the compound shown in the formula XII and cyclobutanone oxime ester are subjected to free radical addition reaction to obtain the compound shown in the formula I, the compound shown in the formula II, the compound shown in the formula III, the compound shown in the formula IV, the compound shown in the formula V or the compound shown in the formula VI. The invention synthesizes various tri-substituted olefin compounds and heterocyclic compounds under the action of light by utilizing the self-designed photocatalyst for the first time. Compared with the prior art, the synthesis method of the tri-substituted olefin compound and the heterocyclic compound has the characteristics of easily obtained raw materials, simple operation, mild reaction conditions, economy, greenness and the like.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthetic catalyst and a catalytic method for various tri-substituted olefin compounds and heterocyclic compounds.
Background
Nitrile is one of the most useful components for the synthesis of various materials, bioactive molecules and natural products (Wiley-VCH, weinheim,5th compl. Rev. Edn,1985, vol. A17, p.363). It is highly desirable to develop a fast and efficient process for obtaining various nitriles. In this case, the cleavage of the carbon-carbon bond of the cyclic ketoxime derivative has become sp-formation since the early studies of Zard (J.Am.chem.Soc.1991, 113, 1055-1057.)) and Uemura (J.Am.chem.Soc.2000, 122,12049-12050 3 A powerful tool for nitrile alkyl radicals to obtain various nitriles (chem.soc.rev.2019, 48,2615-2656 acc.chem.res.2020,53,1066-1083, chem.rev.2021,121, 264-299. In recent years, visible light photooxidation catalysis has been applied under mild conditions to produce cyanoalkyl groups, but these photoelectrocatalytic methods require expensive photocatalysts, transition metal complexes or othersAnd (3) an additive.
Tri-substituted olefins are important organic synthesis units useful for the synthesis of a variety of drugs, materials and fine chemicals (j.med.chem.2003, 46,1484-1491, anti-cancer drugs 2007,18,1039-1044. Meanwhile, heterocyclic compounds are common among natural products and bio-related compounds as a main scaffold for drug and pesticide development (j.med.chem.2014, 57,10257-10274 chem.rev.2015,115,1622-1651 acc.chem.res.2018,51, 1443-1454.. In order to obtain these compounds, the cleavage of the C-C bond of cyclic ketoxime derivatives has been a powerful tool. However, transition metals, photocatalysts and high temperatures are often necessary for these existing strategies.
In summary, these methods use metals, expensive catalysts or excessive alkali, and are not economical and environmentally friendly. Therefore, the development of a new catalytic method for economically and greenly introducing nitrile structural units into organic molecules has very important significance.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a synthetic method of tri-substituted olefin and heterocyclic compounds; the method adopts a brand new organic catalyst to synthesize the tri-substituted olefin and heterocyclic compound molecules containing nitrile structural units under the action of light, and provides a simple, high-efficiency, economic and green synthetic approach for introducing nitrile compounds into the tri-substituted olefin and heterocyclic compounds.
The invention provides a method for synthesizing tri-substituted olefin compounds and heterocyclic compounds, namely a method for synthesizing compounds shown in formula I, formula II, formula III, formula IV, formula V or formula VI, which comprises the following steps:
under the irradiation of blue light, carrying out free radical addition reaction on a compound shown as a formula VII, a compound shown as a formula VIII, a compound shown as a formula IX, a compound shown as a formula X, a compound shown as a formula XI or a compound shown as a formula XII and cyclobutanone oxime ester in an inert atmosphere to obtain a compound shown as a formula I, a compound shown as a formula II, a compound shown as a formula III, a compound shown as a formula IV, a compound shown as a formula V or a compound shown as a formula VI;
in the formula I-formula VI, R is one of mono-substituted or multi-substituted alkyl, mono-substituted or multi-substituted halogen and hydroxyl;
in the formula VII-formula XI, R is one of mono-substituted or multi-substituted alkyl, mono-substituted or multi-substituted halogen and hydroxyl.
As examples, the compounds represented by the formula I are compounds represented by the following formula I-1 to formula I-3:
as examples, the compounds represented by the formula II include the following compounds represented by the formula II-1 to the formula II-3:
as an example, the compound represented by the formula III is any one of a compound represented by the following formula III-1 to a compound represented by the following formula III-3:
as an example, the compound represented by the formula IV is any one of a compound represented by the following formula IV-1 to a compound represented by the following formula IV-4:
as an example, the compound represented by the formula V is any one of a compound represented by the following formula V-1 to a compound represented by the following formula V-4:
as an example, the compound shown in the formula VI is any one of a compound shown in a formula VI-1 to a compound shown in a formula VI-4:
in the above synthesis method, the molar ratio of the compound represented by the formula VII, the compound represented by the formula VIII, the compound represented by the formula IX, the compound represented by the formula X, the compound represented by the formula XI or the compound represented by the formula XII to the cyclic ketoxime ester may be 1.5.
In the above synthesis method, the concentration of the compound represented by the formula VII, the compound represented by the formula VIII, the compound represented by the formula IX, the compound represented by the formula X, the compound represented by the formula XI or the compound represented by the formula XII in the solvent may be 0.1M.
In the above synthesis method, the wavelength of the blue light may be 450nm; the blue light may be provided by a blue LED lamp, which may have a power of 100W.
In the above synthesis method, the temperature of the free radical addition reaction may be 40 to 50 ℃, specifically 45 ℃; the time may be 12 hours.
In the synthesis method, the method further comprises the steps of performing silica gel chromatographic separation on the system after the reaction is finished, and performing reduced pressure distillation after collection; preferably, the stationary phase for silica gel chromatographic separation is SiO 2 (ii) a The mobile phase is a mixed liquid composed of petroleum ether and ethyl acetate in a certain volume ratio.
Compared with the prior art, the technical scheme of the invention has the following advantages:
the method adopts a novel photocatalyst which is independently designed for the first time, and synthesizes the tri-substituted olefin compound and the heterocyclic compound under the action of light. Compared with the prior art, the synthesis method of the tri-substituted olefin and the heterocyclic compound has the characteristics of easily obtained raw materials, simple operation, mild reaction conditions, economy, greenness and the like.
Drawings
FIG. 1 is a synthesis scheme of tri-substituted olefins and heterocyclic compounds in an embodiment of the present invention.
Detailed Description
In order to further illustrate the present invention, the following detailed description of the embodiments of the present invention is provided in conjunction with the accompanying drawings and examples, which should not be construed as limiting the scope of the present invention.
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified. The nuclear magnetic resonance was measured by a japanese electron nuclear magnetic resonance apparatus. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Example 1 Synthesis of Compound represented by formula II-1
The compound shown as the formula II-1 is synthesized according to the synthesis scheme shown as the figure 1, and the specific steps are as follows:
a compound represented by the formula VIII-1 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and toluene (2.0 mL) are added into a reaction tube which is dried in advance under the protection of nitrogen. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =5:1, collecting, and distilling under reduced pressure to obtain a product) to obtain the compound shown in the formula II-1.
The experimental data for structural validation are as follows:
colorless oil(49.3mg,0.154mmol,77％). 1 H NMR(400MHz,CDCl 3 )δ7.44–7.36(m,3H),7.31–7.27(m,2H),7.24–7.21(m,3H),7.20–7.16(m,2H),5.19(t,J＝7.6Hz,1H),4.50(s,2H),2.34–2.28(m,2H),2.21(s,3H),2.15(t,J＝7.2Hz,2H),1.67–1.59(m,2H). 13 C NMR(101MHz,CDCl 3 )δ170.5,140.2,137.6,134.6,129.8,129.1,128.9,128.6,128.4,127.5,119.1,49.0,27.4,25.3,22.4,16.6.IR(ATR):2932,2246,1641,1390,1286,1126,777cm - 1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 22 N 2 ONa + 341.1624,found 341.1621.
the obtained compound is the compound shown as the formula II-1 through verification.
Example 2 Synthesis of Compound represented by the formula II-2
The compound shown as the formula II-2 is synthesized according to the synthesis scheme shown as the figure 1, and the specific steps are as follows:
adding a compound shown in a formula VIII-2 (0.2 mmol), alkyl ketoxime shown in a formula 3 (0.3 mmol), a catalyst shown in a formula 2 (0.04 mmol) and toluene (2.0 mL) into a reaction tube dried in advance under the protection of nitrogen. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =5:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula II-2.
The experimental data for structural validation are as follows:
a colorless oil(49.2mg,0.120mmol,60％). 1 H NMR(400MHz,CDCl 3 )δ8.09(d,J＝8.1Hz,2H),7.33–7.23(m,5H),7.20–7.13(m,2H),5.31(d,J＝7.2Hz,1H),4.51(s,2H),4.44–4.38(m,2H),2.35–2.29(m,2H),2.21(s,3H),2.17(t,J＝7.1Hz,2H),1.68–1.61(m,2H),1.42(t,J＝7.1Hz,3H). 13 C NMR(126MHz,CDCl 3 )δ170.5,166.0,139.5,139.1,137.3,131.3,131.0,130.2,129.1,128.6,128.5,127.6,119.0,61.4,49.2,27.5,25.2,22.4,16.7,14.4.IR(ATR):2932,2245,1712,1643,1388,1271,1103,868cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 24 H 26 N 2 O 3 Na + 413.1836,found 413.1826.
the obtained compound is the compound shown as the formula II-2 through verification.
Example 3 Synthesis of Compound represented by the formula II-3
The compound shown as the formula II-3 is synthesized according to the synthesis scheme shown as the figure 1, and the specific steps are as follows:
adding a compound shown in a formula VIII-3 (0.2 mmol), alkyl ketoxime shown in a formula 3 (0.3 mmol), a catalyst shown in a formula 2 (0.04 mmol) and toluene (2.0 mL) into a reaction tube dried in advance under the protection of nitrogen. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =5:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula II-3.
The experimental data for structural validation are as follows:
a colorless oil(50.4mg,0.154mmol,76％). 1 H NMR(500MHz,CDCl 3 )δ7.31–7.26(m,3H),7.23(d,J＝8.0Hz,2H),7.20–7.16(m,2H),7.13(d,J＝7.9Hz,2H),5.14(t,J＝7.6Hz,1H),4.50(s,2H),2.40(s,3H),2.33–2.29(m,2H),2.21(s,3H),2.15(t,J＝7.1Hz,2H),1.66–1.60(m,2H). 13 C NMR(126MHz,CDCl 3 )δ170.6,140.2,139.2,137.7,131.6,129.6,129.23,129.15,128.6,128.4,127.5,119.2,48.9,27.5,25.4,22.4,21.4,16.7.IR(ATR):2927,2246,1640,1390,1167,819cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 22 H 24 N 2 ONa + 355.1781,found 355.1776.
the obtained compound is the compound shown as the formula II-3 through verification.
Example 4 Synthesis of a Compound represented by the formula III-1
The compound shown in the formula III-1 is synthesized according to a synthesis scheme shown in figure 1, and the specific steps are as follows:
a previously dried reaction tube was charged with a compound represented by the formula IX-1 (0.2 mmol), an alkylketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol), and dimethyl sulfoxide (2.0 mL) under a nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =4:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula iii-1.
The experimental data for structural validation are as follows:
a white solid(32.8mg,0.154mmol,77％). 1 H NMR(400MHz,CDCl 3 )δ7.61(s,1H),7.56–7.44(m,2H),7.37–7.27(m,2H),2.76(t,J＝7.0Hz,2H),2.44(t,J＝7.0Hz,2H),2.10–2.02(m,2H). 13 C NMR(101MHz,CDCl 3 ) δ 161.6,153.5,140.3,131.3,127.6,127.3,124.7,119.3,116.7,30.4,23.8,16.9 (Yu, y.z., was synthesized by iii-1 according to literature reporting procedures; ye, z.p.; xia, p.j.; song, d.; li, x.j.; liu, z.l.; liu, f.; chen, k.; xiang, h.y.; yang, h., j.org.chem.2021,86, 4245-4253).
The obtained compound is the compound shown in the formula III-1 through verification.
Example 5 Synthesis of Compound represented by the formula III-2
The compound shown as the formula III-2 is synthesized according to a synthesis scheme shown as a figure 1, and the specific steps are as follows:
adding a compound represented by the formula IX-2 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol), and dimethyl into a reaction tube dried in advance under the protection of nitrogenAfter sulfoxide (2.0 mL). Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =4:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula iii-2.
The experimental data for structural validation are as follows:
a white solid(27.5mg,0.114mmol,57％). 1 H NMR(400MHz,CDCl 3 )δ7.54(s,1H),7.36(d,J＝8.6Hz,1H),6.87–6.84(m,1H),6.82(d,J＝2.4Hz,1H),3.87(s,3H),2.70(t,J＝7.0Hz,2H),2.42(t,J＝7.0Hz,2H),2.07–2.02(m,2H). 13 CNMR(101MHz,CDCl 3 ) δ 162.4,161.9,155.2,140.5,128.5,123.5,119.4,112.9,112.8,100.6,55.9,30.2,23.9,16.8 (Yu, y.z., was synthesized by iii-1 according to literature reporting procedures; ye, z.p.; xia, p.j.; song, d.; li, x.j.; liu, z.l.; liu, f.; chen, k.; xiang, h.y.; yang, h., j.org.chem.2021,86, 4245-4253).
The obtained compound is the compound shown as the formula III-2 after verification.
Example 6 Synthesis of a Compound represented by the formula III-3
The compound shown in the formula III-3 is synthesized according to a synthesis scheme shown in figure 1, and the specific steps are as follows:
a previously dried reaction tube was charged with a compound represented by the formula IX-3 (0.2 mmol), an alkylketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol), and dimethyl sulfoxide (2.0 mL) under a nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =4:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula iii-3.
The experimental data for structural validation are as follows:
a white solid(24.3mg,0.106mmol,53％). 1 H NMR(400MHz,CD 3 CN)δ7.75(s,1H),7.61(s,1H),7.40(d,J＝8.5Hz,1H),6.82–6.72(m,2H),2.61–2.53(m,2H),2.44(t,J＝7.2Hz,2H),1.94–1.86(m,2H). 13 C NMR(126MHz,CD 3 CN) δ 162.5,160.6,155.8,140.9,129.8,124.3,121.0,113.6,103.0,30.4,24.5,16.9 (Gao, p. was synthesized by iii-1 according to literature procedures; cheng, y.b.; yang, f.; guo, l.n.; duan, x.h., tetrahedron lett.2019,60,150967).
The obtained compound is the compound shown in the formula III-3 through verification.
Example 7 Synthesis of a Compound represented by the formula IV-1
The compound shown as the formula IV-1 is synthesized according to the synthesis scheme shown as the figure 1, and the specific steps are as follows:
a compound represented by the formula X-1 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and acetone (2.0 mL) were added to a reaction tube which had been previously dried under nitrogen atmosphere. The mixture was stirred overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =5:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula iv-1.
The experimental data for structural validation are as follows:
a colorless oil(43.7mg,0.162mmol,81％). 1 H NMR(400MHz,CDCl 3 )δ8.25(d,J＝7.3Hz,1H),7.68–7.64(m,1H),7.49–7.38(m,2H),3.38(s,3H),2.41–2.27(m,1H),2.25–2.12(m,2H),1.94–1.87(m,1H),1.61(s,3H),1.58–1.44(m,2H),1.11–0.86(m,2H). 13 C NMR(101MHz,CDCl 3 )δ176.5,164.4,143.1,134.4,129.2,127.7,125.2,125.0,119.3,47.7,41.8,29.8,27.3,25.4,24.6,16.9 (IV-1 was synthesized according to literature procedures to yield Wang, Z.; yan, X.Y.; he, X.X.; yan X.H.; li, X.Q.; xu, X.S., synlett2020,31, 809-812.).
The obtained compound is the compound shown as the formula IV-1 through verification.
Example 8 Synthesis of a Compound represented by the formula IV-2
The compound shown as the formula IV-2 is synthesized according to the synthesis scheme shown as the figure 1, and the specific steps are as follows:
a compound represented by the formula X-2 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and acetone (2.0 mL) were added to a reaction tube which had been previously dried under nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =5:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula iv-2.
The experimental data for structural validation are as follows:
a colorless oil(40.9mg,0.136mmol,68％). 1 H NMR(500MHz,CDCl 3 )δ8.21(d,J＝8.8Hz,1H),6.98–6.96(m,1H),6.85(s,1H),3.91(s,3H),3.37(s,3H),2.38–2.27(m,1H),2.24–2.14(m,2H),1.90–1.84(m,1H),1.60(s,3H),1.59–1.46(m,2H),1.11–0.90(m,2H). 13 C NMR(126MHz,CDCl 3 ) δ 176.6,164.5,164.0,145.4,131.5,119.4,118.0,113.3,110.5,55.7,47.9,41.9,29.9,27.2,25.4,24.5,16.9 (iv-2 was synthesized according to literature report procedures to give Wang, z.; yan, x.y.; he, x.x.; yan, x.h.; li, x.q.; xu, x.s., synlett2020,31,809-812).
The obtained compound is the compound shown as the formula IV-2 after verification.
Example 9 Synthesis of a Compound represented by the formula IV-3
The compound shown in the formula IV-3 is synthesized according to the synthesis scheme shown in figure 1, and the specific steps are as follows:
a compound represented by the formula X-3 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and acetone (2.0 mL) were added to a reaction tube which had been previously dried under nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =5:1, and after collection, the product is obtained by vacuum distillation) to obtain the compound shown in formula iv-3.
The experimental data for structural validation are as follows:
a yellow oil(34.6mg,0.102mmol,51％). 1 H NMR(400MHz,CDCl 3 )δ8.30(s,1H),7.67(s,1H),3.41(s,3H),2.93–2.81(m,1H),2.35–2.21(m,3H),1.82(s,3H),1.64–1.47(m,2H),1.05–0.77(m,2H). 13 C NMR(126MHz,CDCl 3 )δ176.2,162.2,137.3,137.0,134.6,133.3,128.7,119.3,49.2,36.8,28.0,25.7,25.3,25.0,16.9.IR(ATR):2940,2246,1715,1665,1324,1271,1117,775cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 16 H 16 Cl 2 N 2 O 2 Na + 361.0481,found 361.0479.
the obtained compound is the compound shown as the formula IV-3 after verification.
Example 10 Synthesis of a Compound represented by the formula IV-4
The compound shown in the formula IV-4 is synthesized according to the synthesis scheme shown in FIG. 1, and the specific steps are as follows:
a compound represented by the formula X-4 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and acetone (2.0 mL) were added to a reaction tube which had been previously dried under nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =5:1, and after collection, the product is obtained by vacuum distillation) to obtain the compound shown in formula iv-4.
The experimental data for structural validation are as follows:
a colorless oil(55.0mg,0.160mmol,80％). 1 H NMR(400MHz,CDCl 3 )δ8.27(d,J＝8.0Hz,1H),7.67–7.63(m,1H),7.49–7.37(m,4H),7.33–7.26(m,2H),7.25–7.21(m,1H),5.26(d,J＝13.4Hz,1H),5.15(d,J＝13.7Hz,1H),2.32–2.20(m,1H),2.12–1.97(m,2H),1.93–1.81(m,1H),1.60(s,3H),1.48–1.35(m,2H),0.93–0.76(m,2H). 13 C NMR(101MHz,CDCl 3 ) Delta 176.1,164.1,143.2,137.2,134.4,129.3,128.9,128.5,127.7,127.6,125.1,125.0,119.3,47.6,43.6,42.1,29.3,25.3,24.3,16.8 (iv-4 was synthesized according to literature reported procedures to Wang, z.; yan, x.y.; he, x.x.; yan, x.h.; li, x.q.; xu, X.S., synlett2020,31,809-812)
The obtained compound is the compound shown in the formula IV-4 through verification.
EXAMPLE 11 Synthesis of Compound of formula V-1
The compound of formula V-1 was synthesized according to the synthesis scheme shown in FIG. 1, with the following specific steps:
a compound represented by formula XI-1 (0.2 mmol), an alkyl ketoxime represented by formula 3 (0.3 mmol), a catalyst represented by formula 2 (0.04 mmol), and tetrahydrofuran (2.0 mL) were added to a previously dried reaction tube under a nitrogen atmosphere. The mixture was stirred overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula v-1.
The experimental data for structural validation are as follows:
a colorless oil(45.5mg,0.138mmol,69％). 1 H NMR(400MHz,CDCl 3 )δ8.53–8.46(m,1H),7.88–7.78(m,1H),7.65–7.56(m,1H),7.53–7.50(m,1H),7.48(d,J＝3.7Hz,1H),7.47–7.41(m,3H),2.51–2.43(m,1H),2.25–2.10(m,2H),2.10–2.00(m,1H),1.73(s,3H),1.61–1.48(m,2H),1.16–0.94(m,2H). 13 CNMR(101MHz,CDCl 3 )δ173.1,149.8,144.2,141.2,132.3,131.4,128.1,126.21,126.17,126.0,125.8,123.1,120.0,119.3,115.8,49.4,41.6,29.5,25.5,24.7,16.9.IR(ATR):2931,2245,1712,1613,1583,1450,1352,1166,962,742cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 19 N 3 ONa + 352.1420,found 352.1417.
the obtained compound is the compound shown as the formula V-1 after verification.
Example 12 Synthesis of a Compound represented by the formula V-2
The compound shown in the formula V-2 is synthesized according to the synthesis scheme shown in FIG. 1, and the specific steps are as follows:
a compound represented by the formula XI-2 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and tetrahydrofuran (2.0 mL) were added to a previously dried reaction tube under a nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula v-2.
The experimental data for structural validation are as follows:
a white solid(47.2mg,0.116mmol,58％). 1 H NMR(400MHz,CDCl 3 )δ8.42–8.34(m,1H),7.95–7.92(m,1H),7.85–7.82(m,1H),7.49–7.45(m,3H),7.40–7.36(m,1H),2.51–2.39(m,1H),2.27–2.08(m,2H),2.08–1.96(m,1H),1.73(s,3H),1.63–1.44(m,2H),1.05(m,2H). 13 C NMR(126MHz,CDCl 3 )δ172.1,147.2,144.2,143.7,135.5,131.6,130.7,126.6,126.2,125.5,122.5,121.7,121.0,119.3,115.8,49.7,41.9,29.6,25.4,24.5,16.9.IR(ATR):2925,2245,1704,1562,1447,1329,1125,966,749cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 18 BrN 3 ONa + 430.0526,found 430.0519.
the obtained compound is the compound shown as the formula V-2 after verification.
Example 13 Synthesis of a Compound represented by the formula V-3
The compound shown as the formula V-3 is synthesized according to a synthesis scheme shown as a figure 1, and the specific steps are as follows:
a compound represented by the formula XI-3 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and tetrahydrofuran (2.0 mL) were added to a previously dried reaction tube under a nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then, the reaction mixture was subjected to distillation under reduced pressure and silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound shown in formula v-3.
The experimental data for structural validation are as follows:
a colorless oil(53.3mg,0.150mmol,75％). 1 H NMR(400MHz,CDCl 3 )δ8.37–8.30(m,2H),7.81(d,J＝8.1Hz,1H),7.50–7.38(m,2H),7.21(s,1H),2.60(s,3H),2.50–2.46(m,2H),2.42(s,3H),2.25–2.08(m,2H),1.81(s,3H),1.64–1.46(m,2H),1.09–0.94(m,2H). 13 C NMR(126MHz,CDCl 3 )δ174.3,150.6,144.4,138.1,137.9,136.0,135.5,131.4,126.2,125.5,125.4,123.7,119.8,119.3,115.9,50.6,38.0,26.7,25.6,25.2,23.0,20.7,16.9.IR(ATR):2922,2245,1722,1540,1450,1364,1324,1121,863,772cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 23 H 23 N 3 ONa + 380.1733,found 380.1728.
the obtained compound is the compound shown as the formula V-3 after verification.
Example 14 Synthesis of a Compound represented by the formula V-4
The compound shown as the formula V-4 is synthesized according to a synthesis scheme shown as a figure 1, and the specific steps are as follows:
a compound represented by the formula XI-4 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and tetrahydrofuran (2.0 mL) were added to a previously dried reaction tube under a nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and after collection, the product is obtained by reduced pressure distillation) to obtain the compound represented by formula v-4.
The experimental data for structural validation are as follows:
a white solid(45.0mg,0.110mmol,55％). 1 H NMR(400MHz,CDCl 3 )δ8.47–8.45(m,1H),8.21(d,J＝8.5Hz,1H),7.96(d,J＝1.8Hz,1H),7.64–7.60(m,1H),7.55–7.49(m,2H),7.48–7.47(m,1H),2.48–2.42(m,1H),2.25–2.10(m,2H),2.08–2.02(m,1H),1.73(s,3H),1.64–1.45(m,2H),1.13–0.95(m,2H). 13 CNMR(126MHz,CDCl 3 )δ173.0,150.8,145.6,141.4,132.6,130.4,128.7,128.2,126.4,126.0,123.0,122.7,119.2,116.9,49.5,41.6,29.5,25.4,24.6,16.9.IR(ATR):2926,2242,1705,1604,1578,1445,1347,1325,1157,969,776cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 18 BrN 3 ONa + 430.0526,found 430.0522.
the obtained compound is the compound shown as the formula V-4 after verification.
Example 15 Synthesis of a Compound of formula VI-1
The compound shown as the formula VI-1 is synthesized according to a synthesis scheme shown as a figure 1, and the specific steps are as follows:
a compound represented by the formula XII-1 (0.2 mmol), an alkylketoxime represented by the formula 4 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and dimethyl sulfoxide (2.0 mL) were added to a reaction tube which had been dried in advance under a nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and the product is obtained by vacuum distillation after collection) to obtain the compound shown in formula vi-1.
The experimental data for structural validation are as follows:
a colorless oil(isolated as an inseparable mixture,dr＝1:1,55.9mg,0.178mmol,89％). 1 H NMR(400MHz,CDCl 3 )δ7.31–7.27(m,2H),7.16(d,J＝7.3Hz,2H),7.10–7.07(m,2H),6.86(d,J＝7.8Hz,2H),4.20–4.14(m,4H),3.22(d,J＝1.2Hz,6H),2.66–2.40(m,6H),1.99–1.85(m,2H),1.85–1.70(m,2H),1.51–1.42(m,1H),1.36(d,J＝2.6Hz,6H),1.34–1.24(m,9H). 13 C NMR(126MHz,CDCl 3 )δ180.07,180.02,172.3,172.2,143.4,143.3,133.21,133.15,128.27,128.25,122.94,122.91,122.60,122.58,117.7,117.6,108.4,61.6,48.1,48.0,41.6,41.5,35.0,34.8,26.5,26.4,26.3,24.02,23.92,19.5,19.1,14.3.IR(ATR):2928,2247,1700,1612,1471,1421,1376,1181,1125,935,755cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 18 H 22 N 2 O 3 Na + 337.1523,found 337.1517.
the obtained compound is the compound shown in the formula VI-1 after verification.
Example 16 Synthesis of a Compound of the formula VI-2
The compound shown as the formula VI-2 is synthesized according to a synthesis scheme shown as a figure 1, and the specific steps are as follows:
the reaction tube dried in advance is put under nitrogenA compound represented by the formula XII-1 (0.2 mmol), an alkylketoxime represented by the formula 5 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol), and dimethyl sulfoxide (2.0 mL) were added under protection. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and the product is obtained by vacuum distillation after collection) to obtain the compound shown in formula vi-2.
The experimental data for structural validation are as follows:
a colorless oil(isolated as an inseparable mixture,dr＝1:1,49.2mg,0.154mmol,77％). 1 H NMR(400MHz,CDCl 3 )δ7.37–7.26(m,8H),7.18–7.02(m,7H),6.97–6.96(m,1H),6.88–6.85(m,2H),3.22(d,J＝6.5Hz,6H),2.87–2.68(m,2H),2.50–2.42(m,4H),1.91–1.60(m,4H),1.57–1.33(m,4H),1.28(d,J＝11.3Hz,6H). 13 C NMR(126MHz,CDCl 3 )δ180.4,180.2,143.3,143.2,141.0,140.8,133.6,133.4,129.03,129.01,128.1,127.64,127.59,127.3,127.2,122.8,122.7,122.5,122.4,118.3,108.2,48.12,48.06,42.3,42.2,35.8,35.7,29.5,29.3,25.5,25.1,24.1,23.9.IR(ATR):2925,2245,1702,1611,1492,1453,1348,1066,753cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 21 H 22 N 2 ONa + 341.1624,found 341.1618.
the compound is the compound shown in the formula VI-2 after verification.
Example 17 Synthesis of a Compound represented by the formula VI-3
The compound shown as the formula VI-3 is synthesized according to a synthesis scheme shown as a figure 1, and the specific steps are as follows:
a compound represented by the formula XII-1 (0.2 mmol), an alkylketoxime represented by the formula 6 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and dimethyl sulfoxide (2.0 mL) were added to a reaction tube which had been dried in advance under a nitrogen atmosphere. Stirring overnight at 45 ℃ on a 100W blue LED (450 nm) lamp (12h) .1. The Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and the product is obtained by vacuum distillation after collection) to obtain the compound shown in formula vi-3.
The experimental data for structural validation are as follows:
a colorless oil(isolated as an inseparable mixture,dr＝1:1,52.2mg,0.150mmol,75％). 1 H NMR(500MHz,CDCl 3 )δ7.31–7.27(m,5H),7.25–7.24(m,1H),7.20(d,J＝7.4Hz,1H),7.17–7.04(m,3H),6.99–6.92(m,2H),6.87(d,J＝7.8Hz,2H),6.85–6.80(m,4H),3.94–3.90(m,2H),3.81–3.78(m,1H),3.76–3.69(m,1H),3.23(d,J＝4.7Hz,6H),2.50–2.47(m,4H),2.11–1.94(m,4H),1.91–1.79(m,2H),1.37(d,J＝5.6Hz,6H),1.28–1.06(m,4H). 13 C NMR(126MHz,CDCl 3 )δ180.34,180.32,158.5,158.4,143.4,143.3,133.4,133.3,129.7,128.22,128.19,123.0,122.9,122.7,122.6,121.4,118.3,118.1,114.68,114.65,108.4,68.8,68.2,48.25,48.22,35.9,35.8,35.4,26.4,25.6,25.5,24.2,24.0,19.8,19.4.IR(ATR):2926,2245,1702,1611,1492,1469,1238,1124,1018,749cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 22 H 24 N 2 O 2 Na + 371.1730,found 371.1723.
the obtained compound is the compound shown in the formula VI-3 after verification.
Example 18 Synthesis of a Compound represented by the formula VI-4
The compound shown as the formula VI-4 is synthesized according to a synthesis scheme shown as a figure 1, and the specific steps are as follows:
a compound represented by the formula XII-1 (0.2 mmol), an alkylketoxime represented by the formula 7 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and dimethyl sulfoxide (2.0 mL) were added to a reaction tube which had been dried in advance under a nitrogen atmosphere. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then subjecting the reaction mixture to reduced pressure distillation and silica gel chromatographySeparation (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and the product is obtained by vacuum distillation after collection) to obtain the compound shown in formula vi-4.
The experimental data for structural validation are as follows:
a white solid(isolated as an inseparable mixture,dr＝1.3:1,33.9mg,0.102mmol,51％). 1 H NMR(400MHz,CDCl 3 )7.36–7.32(m,1H),7.31–7.27(m,1H),7.23–7.11(m,8H),7.01–6.97(m,1H),6.93–6.90(m,2H),6.87–6.78(m,3H),6.77–6.73(m,2H),3.25(d,J＝7.5Hz,6H),2.49(dd,J＝13.9,4.1Hz,1H),2.33–1.91(m,9H),1.89–1.80(m,2H),1.73–1.59(m,1H),1.53–1.40(m,3H),1.38(s,3H),1.31(s,3H),1.28–1.21(m,1H),1.17–1.07(m,1H). 13 C NMR(126MHz,CDCl 3 )δ180.73,180.68,143.4,143.3,139.7,139.6,133.4,133.0,129.1,129.0,128.6,128.5,128.4,128.2,126.3,123.1,123.0,122.8,119.8,119.5,108.54,108.45,48.2,47.8,41.8,41.7,41.0,40.3,36.3,36.2,29.5,29.4,26.49,26.45,25.8,25.2,14.6,14.5.IR(ATR):2927,2247,1688,1612,1525,1449,1364,1254,1164,1017,745cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 22 H 24 N 2 ONa + 355.1781,found355.1775.
the obtained compound is the compound shown in the formula VI-4 after verification.
Example 19 Synthesis of Compound represented by the formula I-1
The compound shown as the formula I-1 is synthesized according to a synthesis scheme shown as a figure 1, and the specific steps are as follows:
a compound represented by the formula VII-1 (0.2 mmol), an alkyl ketoxime represented by the formula 3 (0.3 mmol), a catalyst represented by the formula 2 (0.04 mmol) and acetone (2.0 mL) were added to a reaction tube which had been previously dried under the protection of nitrogen. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then, the reaction mixture was subjected to distillation under reduced pressure and silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum etherEthyl acetate =3:1, collected and distilled under reduced pressure to obtain the product) to obtain the compound represented by formula i-1.
The experimental data for structural validation are as follows:
a colorless oil(36.1mg,0.146mmol,73％). 1 H NMR(400MHz,CDCl 3 )δ7.40–7.35(m,2H),7.34–7.31(m,1H),7.29–7.18(m,5H),7.18–7.12(m,2H),6.01(t,J＝7.4Hz,1H),2.31–2.23(m,4H),1.83–1.75(m,2H). 13 C NMR(101MHz,CDCl 3 ) Delta 143.8,142.2,139.7,129.8,128.5,128.3,127.3,127.3,126.7,119.7,28.8,25.8,16.8 (i-1 was synthesized according to literature procedures to give Zhao, b.; shi, Z., angew.chem.Int.Ed.2017,56, 12727-12731.)
The obtained compound is the compound shown as I-1 through verification.
Example 20 Synthesis of a Compound represented by the formula I-2
The compound shown as the formula I-2 is synthesized according to a synthesis scheme shown as a figure 1, and the specific steps are as follows:
the compound represented by the formula VII-2 (0.2 mmol), the alkyl ketoxime represented by the formula 3 (0.3 mmol), the catalyst represented by the formula 2 (0.04 mmol) and acetone (2.0 mL) were added to a reaction tube dried in advance under the protection of nitrogen. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and the product is obtained by vacuum distillation after collection) to obtain the compound shown in formula i-2.
The experimental data for structural validation are as follows:
a colorless oil(42.3mg,0.150mmol,75％). 1 H NMR(500MHz,CDCl 3 )δ7.17–7.14(m,2H),7.13–7.04(m,4H),6.98–6.94(m,2H),5.95(t,J＝7.4Hz,1H),2.32(t,J＝7.2Hz,2H),2.28–2.24(m,2H),1.83–1.77(m,2H). 13 C NMR(126MHz,CDCl 3 ) δ 162.4 (d, J =248.2 Hz), 162.2 (d, J =248.2 Hz), 142.0,138.3 (d, J =3.4 Hz), 135.4 (d, J =3.5 Hz), 131.4 (d, J =7.9 Hz), 128.9 (d, J =7.9 Hz), 127.0,119.5,115.6 (d, J =21.3 Hz), 115.2 (d, J =21.5 Hz), 28.8,25.8,16.9 (i-2 synthesized according to literature report procedures to yield Yu, x.y.; chen, j.r.; wang, p.z.; yang, m.n.; liang, d.; xiao, w.j., angelw.chem.int.ed.2018, 57, 738-743.)
The obtained compound is the compound shown as I-2 through verification.
Example 21 Synthesis of a Compound represented by the formula I-3
The compound shown as the formula I-3 is synthesized according to the synthesis scheme shown as the figure 1, and the specific steps are as follows:
the compound represented by the formula VII-3 (0.2 mmol), the alkyl ketoxime represented by the formula 3 (0.3 mmol), the catalyst represented by the formula 2 (0.04 mmol) and acetone (2.0 mL) were added to a reaction tube dried in advance under the protection of nitrogen. Stir overnight (12 h) at 45 ℃ on a 100W blue LED (450 nm) lamp. Then the reaction mixture is distilled under reduced pressure and separated by silica gel chromatography (stationary phase of column chromatography: siO) 2 And (3) mobile phase: petroleum ether/ethyl acetate =3:1, and the product is obtained by vacuum distillation after collection) to obtain the compound represented by formula i-3.
The experimental data for structural validation are as follows:
a colorless oil(46.8mg,0.152mmol,76％). 1 H NMR(500MHz,CDCl 3 )δ7.17–7.11(m,2H),7.10–7.03(m,2H),6.94–6.87(m,2H),6.83–6.77(m,2H),5.87(t,J＝7.4Hz,1H),3.83(s,3H),3.78(s,3H),2.30(t,J＝7.3Hz,2H),2.28–2.23(m,2H),1.81–1.75(m,2H). 13 C NMR(126MHz,CDCl 3 )δ159.1,158.8,142.9,135.4,132.3,131.0,128.5,124.8,119.8,113.8,113.6,55.40,55.36,28.8,26.0,16.8.IR(ATR):2934,2246,1604,1508,1241,1170,1028,832cm -1 .HRMS(ESI)m/z:[M+Na] + calcd.for C 20 H 21 NO 2 Na + 330.1465,found 330.1461.
the obtained compound is the compound shown as I-3 through verification.
Although the present invention has been described in detail with reference to the above embodiments, it is only a part of the embodiments of the present invention, not all of the embodiments, and other embodiments can be obtained without inventive step according to the embodiments, and the embodiments are within the scope of the present invention.
Claims (9)
1. An organic catalyst for catalyzing trisubstituted olefin and/or heterocyclic compounds to introduce nitrile compounds is characterized in that the structural formula of the organic catalyst is shown as formula 2;
2. a method for introducing nitrile compounds into tri-substituted olefins and/or heterocyclic compounds in a catalytic manner, which is characterized in that under the irradiation of blue light, raw materials, the organic catalyst of claim 1 and cyclobutanone oxime ester are subjected to free radical addition reaction to obtain the tri-substituted olefins and/or heterocyclic compounds introduced with the nitrile compounds.
3. The process according to claim 2, wherein the raw material comprises a compound represented by the formula VII, a compound represented by the formula VIII, a compound represented by the formula IX, a compound represented by the formula X, a compound represented by the formula XI or a compound represented by the formula XII;
in the formulas VII-XI, R is one of mono-substituted or multi-substituted alkyl, mono-substituted or multi-substituted halogen and hydroxyl.
4. The method according to claim 2, wherein the tri-substituted olefin compound and/or heterocyclic compound into which the nitrile compound is introduced comprises a compound of formula i, a compound of formula ii, a compound of formula iii, a compound of formula iv, a compound of formula v, or a compound of formula vi;
5、
in the formula I-formula VI, R is one of mono-substituted or polysubstituted alkyl, mono-substituted or polysubstituted halogen and hydroxyl.
5. The method of claim 2, wherein the free radical addition reaction is carried out in an inert atmosphere.
6. The process of claim 2, wherein the molar ratio of starting material to cyclic ketoxime ester is 1.
7. The process of claim 2 or 6, wherein the concentration of the starting material in the solvent is 0.1M.
8. The method of claim 2, wherein the blue light has a wavelength of 450 to 456nm.
9. The method of claim 2, wherein the free radical addition reaction is carried out at a temperature of 40 to 50 ℃ for 12 hours.
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