CN117800801A - Method for synthesizing monofluoroolefins compound - Google Patents
Method for synthesizing monofluoroolefins compound Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 29
- 150000001875 compounds Chemical class 0.000 title claims abstract description 25
- 230000002194 synthesizing effect Effects 0.000 title claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 46
- 239000003446 ligand Substances 0.000 claims abstract description 22
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 14
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000010438 heat treatment Methods 0.000 claims abstract description 12
- 239000004246 zinc acetate Substances 0.000 claims abstract description 12
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910000077 silane Inorganic materials 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
- 150000001336 alkenes Chemical class 0.000 claims abstract description 8
- 229940125898 compound 5 Drugs 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 87
- 239000003960 organic solvent Substances 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 238000006467 substitution reaction Methods 0.000 claims description 14
- -1 trifluoromethoxy, t-butyl formate Chemical compound 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 150000005347 biaryls Chemical group 0.000 claims description 6
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 150000002430 hydrocarbons Chemical class 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 claims description 4
- 229940125904 compound 1 Drugs 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- 125000005336 allyloxy group Chemical group 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 claims description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical group ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 2
- 229940125782 compound 2 Drugs 0.000 claims description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- VKWJMTLAAJULGF-UHFFFAOYSA-N methoxymethyl formate Chemical compound COCOC=O VKWJMTLAAJULGF-UHFFFAOYSA-N 0.000 claims description 2
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical group FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims description 2
- HWPXFNSLJBAROC-UHFFFAOYSA-N phenoxymethyl formate Chemical compound O=COCOC1=CC=CC=C1 HWPXFNSLJBAROC-UHFFFAOYSA-N 0.000 claims description 2
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 abstract description 12
- 239000000758 substrate Substances 0.000 abstract description 6
- 229910052731 fluorine Inorganic materials 0.000 abstract description 5
- 239000011737 fluorine Substances 0.000 abstract description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 238000010504 bond cleavage reaction Methods 0.000 abstract description 2
- 229940126214 compound 3 Drugs 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 47
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- 239000000203 mixture Substances 0.000 description 20
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 20
- 238000010898 silica gel chromatography Methods 0.000 description 19
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 12
- 239000012300 argon atmosphere Substances 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000011701 zinc Substances 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 238000010189 synthetic method Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 5
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 4
- 241000282326 Felis catus Species 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001212 derivatisation Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006115 defluorination reaction Methods 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012803 optimization experiment Methods 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 1
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- 229940126650 Compound 3f Drugs 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
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- 230000007547 defect Effects 0.000 description 1
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- 239000012467 final product Substances 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
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- IYRGXJIJGHOCFS-UHFFFAOYSA-N neocuproine Chemical compound C1=C(C)N=C2C3=NC(C)=CC=C3C=CC2=C1 IYRGXJIJGHOCFS-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of monofluoroolefin compounds, and belongs to the technical field of organic synthesis. Trifluoromethyl substituted olefin 1 and silane 2 react in dimethyl sulfoxide solvent with zinc acetate as catalyst under heating in the presence of different ligands to realize C (sp 3 ) F bond and C (sp) 2 ) -F bond cleavage to give trisubstituted (E) -monofluoroolefin compound 3; when the olefin substrate is the gem-difluoroolefin 4, the di/tri-substituted (E) -monofluoroolefin compound 5 is also obtained in a higher yield and excellent stereoselectivity. The synthesis method has the advantages of low catalyst cost, simple and easily obtained raw materials, good substrate applicability, and the synthesized product is a valuable fluorinated member, thereby providing a new method for modifying fluorine-containing molecules.
Description
Technical Field
The invention relates to a synthesis method of di/tri-substituted (E) -monofluoroolefin compounds, belonging to the technical field of organic synthesis.
Background
The fluorine-containing organic molecules have unique biological and chemical characteristics and have wide application in developing new materials, medicines and agricultural chemicals. Although many organofluorine compounds have been synthesized, the stability of the C-F bond presents challenges for their degradation. Efficient defluorination and functionalization of off-the-shelf fluorochemicals is an attractive route to the recovery of organofluorine compounds. However, the search for ways to activate these bonds, especially to achieve a highly stereoselective cleavage of the C-F bonds in a one-step reaction, remains an active area of research due to the high dissociation energy of the C-F bonds.
Fluorine substituted olefins play a key role not only in the synthesis of high value organofluorine compounds, but also in various applications related to drug development. Currently scientists have made significant progress in activating the C-F bonds in fluoroolefins to form C-C, C-O or C-N bonds. However, due to the small size of the hydrogen atoms, achieving precise stereoselectivity in Hydrodefluorination (HDF) reactions of fluoroolefins is very challenging. The stereoselective Hydrodefluorination (HDF) of fluoroolefins has attracted considerable attention, especially in the production of monofluoroolefins.
Monofluoroolefins are an important class of fluoroolefins, similar to amide groups, typically present in reactive compounds. The Z-type and E-type isomers of the derivatives show different biological activities and have potential application prospects in pharmaceutical chemistry and material science. In addition, monofluoroolefins are also very valuable fluorinated members in the synthesis of organofluorine compounds. Thus, there is a need to explore a simpler, more practical, more economically viable hydrodefluorination (HD F) reaction with high stereoselectivity.
Disclosure of Invention
To overcome the technical defects, silane is utilized forHydrodefluorination (HDF) reactions are a promising method for replacing C-F bonds with C-H bonds. The invention provides a method for synthesizing monofluoroolefins by zinc-catalyzed high-stereoselectivity hydrodefluorination reaction of fluoroolefins and polyfluoroaromatic hydrocarbons. The reaction is achieved by hydride addition in the silane. Trifluoromethyl substituted olefin 1 and silane 2 react in dimethyl sulfoxide solvent with zinc acetate as catalyst under heating in the presence of different ligands to realize C (sp 3 ) F bond and C (sp) 2 ) -F bond cleavage to give trisubstituted (E) -monofluoroolefin compound 3; when the olefin substrate is the gem-difluoroolefin 4, the di/tri-substituted (E) -monofluoroolefin compound 5 is also obtained in a higher yield and excellent stereoselectivity. The synthesis method has the advantages of low catalyst cost, simple and easily obtained raw materials, good substrate applicability, and the synthesized product is a valuable fluorinated member, thereby providing a new method for modifying fluorine-containing molecules.
The invention discloses a method for synthesizing monofluoroolefins, which comprises the following steps:
in the method A, trifluoromethyl substituted olefin 1 and silane 2 react in an organic solvent under heating in the presence of a ligand by taking zinc acetate as a catalyst to obtain trisubstituted (E) -monofluoroolefin compounds 3; the reaction equation is expressed as:
wherein: r is selected from H or cyclopropane; ar is selected from substituted or unsubstituted phenyl, naphthyl, heteroaryl, substituted or unsubstituted biaryl; silane 2 is selected from diphenylsilane or phenylsilane;
in the method B, the gem-difluoro olefin 4 and diphenyl silane 2a react in an organic solvent under heating in the presence of a ligand by taking zinc acetate as a catalyst to obtain a di/tri-substituted (E) -difluoro olefin compound 5; the reaction equation is expressed as:
wherein: r is R 1 Selected from hydrogen, methyl, propyl, phenyl, ethyl formate; ar (Ar) 1 Selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted heteroaryl, and substituted or unsubstituted biaryl.
Further, in the above technical scheme, the substitution in the substituted or unsubstituted phenyl refers to substitution of the same or different substituent at any position of the phenyl by one or more of the following groups: halogen, methyl, trifluoromethoxy, t-butyl formate, diphenylamino, methoxy, t-butyl, phenyl, phenoxy, methyl formate, neopentyl; the substitution in the substituted or unsubstituted naphthyl refers to substitution at any position of the naphthyl by one or more of the following groups, the same or different substituents: methoxy, benzyloxy, allyloxy; the heteroaryl is selected from quinolinyl, indolyl, benzofuranyl, benzothienyl; the substituted heteroaryl is selected from phenyl substituted thienyl, chlorobenzene substituted thienyl, fluorobenzene substituted furyl; the substitution in the substituted or unsubstituted biaryl refers to substitution at any position of the phenyl group with one or more of the following groups, the same or different substituents: methyl, methoxy, methyl formate, halogen, trifluoromethyl.
Further, in the above technical solution, the organic solvent is selected from DMSO, DMF, DCE, THF, dimethylacetamide, ethylene glycol dimethyl ether, toluene, methanol, t-butyl methyl ether or 1, 4-dioxane.
Further, in the above technical scheme, the ligand is a compound shown in the following structure:
further, in the above technical scheme, in method a, the ligand is selected from Xanphos; in Process B, the ligand is selected from PPh 3 。
Further, in the technical scheme, the molar ratio of the compound 1 to the compound 2 is 1:3; the mol ratio of the compound 4 to the compound 2a is 1:1-2; the molar ratio of the compound 1 or 4, zinc acetate and the ligand is 1:0.1-0.2:0.1-0.2.
Further, in the above technical scheme, the heating reaction temperature is 50-130 ℃.
Further, in the above technical scheme, the reaction is performed under the protection of inert gas.
The invention also provides a method for synthesizing the tetrafluoroaryl compound 7, which comprises the following steps: the preparation method comprises the steps of (1) heating polyfluoroaromatic hydrocarbon 6 and diphenyl silane 2a in a DMSO solvent by taking zinc acetate as a catalyst and triphenylphosphine as a ligand to react to obtain hydrodefluorination compound 7; the reaction equation is expressed as:
wherein: r is R 2 Selected from trifluoromethyl or pentafluorophenyl.
Further, in the technical scheme, the molar ratio of the compound 6 to the compound 2a is 1:1; the mol ratio of the compound 6 to the zinc acetate to the triphenylphosphine is 1:0.1:0.1; the heating reaction temperature is 50-60 ℃; the reaction is carried out under the protection of inert gas.
The invention has the beneficial effects that:
A. the catalyst is cheap and easy to obtain, has good functional group compatibility and wide substrate application range, and synthesizes a plurality of di-substituted or tri-substituted (E) -monofluoroolefins with higher application value with higher yield and excellent stereoselectivity.
B. The method can also be applied to hydrodefluorination reaction of polyfluoroaromatic hydrocarbon. The method provides an attractive way for degrading C-F bonds and recycling organic fluorides, and also provides a novel method for modifying fluorine-containing molecules.
Detailed Description
The present invention will be further described with reference to the following specific examples, which are not intended to limit the invention in any way.
General synthesis method A for Hydrogenation Defluorination (HDF) reaction of trifluoromethyl substituted olefin
Under argon atmosphere, under 25mL of resistantZn (OAc) is added into the pressure pipe 2 (3.7 mg,0.02 mmol), xantphos (11.6 mg,0.02 mmol) and DMSO (2.0 mL), the reaction solution was stirred at room temperature for 30 minutes, and then successively adding Ph to the reaction solution 2 SiH 2 (110.6 mg,0.6 mmol) and trifluoromethylalkene 1 (0.2 mmol), the reaction tube was sealed and placed in an oil bath at 120℃and stirred for 24 hours. After the reaction, the reaction mixture was quenched with water (2.0 mL) and extracted with methylene chloride, the obtained organic layer was dried over anhydrous sodium sulfate, filtered, the organic solvent was removed under reduced pressure to obtain a crude product, and finally the monofluoroolefin products 3a-3p were purified by column chromatography.
Example 1 Condition optimization experiment
Catalyst cat (10 mmol), ligand L (10 mmol%) and solvent (2.0 mL) were added to a 25mL pressure-resistant tube under argon atmosphere, the reaction was stirred at room temperature for 30 minutes, then silane 2 (0.6 mmol) and trifluoromethylolefin 1a (0.2 mmol) were added in this order to the reaction, and after the addition, the reaction tube was sealed and placed in an oil bath at T ℃ and stirred for 24 hours. After the reaction was completed, the reaction mixture was quenched with water (2.0 mL), extracted with methylene chloride, and the obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the organic solvent was removed under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography to obtain compounds 3a and 3a'. The results are shown in the following table:
a reaction conditions 1a (0.20 mmol), 2 (0.60 mmol), catalyst cat (10 mmol), ligand L (10 mmol), solvent (2.0 mL), reaction under argon for 24 h, yield and E/Z ratio were based on benzotrifluoride (0.1 mmol) as internal standard, using 19 F NMR measurement. b 2a(0.40mmol)。 c 2a(0.80mmol)。 d 2a(0.20mmol)。 e CsOAc (0.02 mmol) is added.
The optimal reaction temperature was determined to be 120℃by examining the reaction temperature (entries 1-5); ligand selection has a significant effect on the efficiency of target product formation (entries 6-10), and the optimal ligand is determined to be Xanphos by screening; zn (OAc) was found by examining the catalyst 2 The highest catalytic efficiency (entries 11-19); the optimal reaction solvent was determined to be DMSO by examining the solvent (entries 20-23); and Ph 2 SiH 2 In contrast, other silane substrates such as (MeO) 2 MeSiH and PhSiH 3 Exhibit lower reactivity (entries 24-26).
Example 2
The following products were prepared by the general synthetic method A, except for the reaction conditions specifically marked or indicated.
a Reaction conditions 1 (0.20 mmol), ph 2 SiH 2 (0.60mmol),Zn(OAc) 2 (0.02 mmol), xantphos (0.02 mmol), DMSO (2.0 mL), 120℃under argon protection for 24 hours, isolation yield and E/Z ratio pass 19 F NMR measurement. b Nuclear magnetic yield. c Reaction conditions PhSiH 3 (0.60mmol),Zn(OAc) 2 (0.04 mmol), xantphos (0.04 mmol), naOAc (1.0 eq.) and nuclear magnetic yield, 130 ℃. d Reaction conditions PhSiH 3 (0.60 mmol), naOAc (1.0 eq.) and nuclear magnetic yield, 120℃and 1pE/Z ratio 74/26.
Aryl para is an electron donating group (3 f and 3 g) shows lower reaction efficiency, which suggests a unique reaction pathway involving hydride addition during the reaction.
Example 3
General synthesis method a, purified by silica gel column chromatography (PE). A colorless oil; 32.4mg (yield 87%, E/z=85/15); 1 H NMR(400MHz,CDCl 3 )δ(E isomer)7.85-7.79(m,3H),7.74(s,1H),7.49-7.44(m,3H),7.06(dq,J＝84.8,1.6Hz,1H),2.16(dd,J＝3.8,1.6Hz,3H).HRMS(ESI,m/z):calcd for C 13 H 12 F + [M+H] + :187.0918,found 187.0946.
example 4
Zn (OAc) was added to a 25mL pressure-resistant tube under an argon atmosphere 2 (7.3 mg,0.04 mmol), xantphos (23.1 mg,0.04 mmol), naOAc (16.4 mg,0.2 mmol) and DMSO (2.0 mL), and the reaction solution was stirred at room temperature for 30 minutes, and then PhSiH was added to the reaction solution in this order 3 (64.9 mg,0.6 mmol) and trifluoromethylalkene 1f (0.2 mmol), the reaction tube was sealed and placed in an oil bath at 130℃and stirred for 24 hours. After the reaction, the reaction mixture was quenched with water (2.0 mL), extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and the organic solvent was removed under reduced pressure to give a crude product, which was purified by silica gel column chromatography (PE: dcm=8:1) to give compound 3f. A colorless oil; nuclear magnetic yield 56%, E/z=83/17; 1 H NMR(400MHz,CDCl 3 )δ(E isomer)7.25-7.21(m,2H),6.89-6.85(m,2H),6.85(dq,J＝86.0,1.6Hz,1H),3.81(s,3H),2.01(dd,J＝3.8,1.6Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ(E isomer)159.2,145.3(d,J＝256.4Hz),130.1(d,J＝8.7Hz),127.1(d,J＝3.0Hz),119.6(d,J＝9.6Hz),114.1,55.4,12.5(d,J＝5.8Hz). 19 F NMR(376MHz,CDCl 3 )(mixture of isomers)δ(Zisomer)-130.31(dq,J＝84.6,4.8Hz)；(E isomer)-133.01(dq,J＝86.0,3.8Hz).HRMS(ESI,m/z):calcd for C 10 H 12 FO + [M+H] + :167.0867,found 167.0876.
example 5
General synthesis method a was purified by silica gel column chromatography (PE: ea=10:1). A colorless oil; 17.2mg (yield 46%, E/z=75/25); 1 H NMR(400MHz,CDCl 3 )δ(E isomer)8.90(d,J＝2.3Hz,1H),8.09(d,J＝8.4Hz,1H),8.01(d,J＝2.3Hz,1H),7.81(d,J＝8.1Hz,1H),7.71-7.67(m,1H),7.57-7.53(m,1H),7.09(dq,J＝83.6,1.6Hz,1H),2.16(dd,J＝3.8,1.6Hz,3H). 13 CNMR(101MHz,CDCl 3 )δ(E isomer)148.5(d,J＝2.2Hz),147.5,147.1(d,J＝261.0Hz),132.3(d,J＝4.5Hz),130.6(d,J＝9.0Hz),129.5,129.3,128.0,127.9,127.2,117.7(d,J＝11.0Hz),12.2(d,J＝5.8Hz). 19 F NMR(376MHz,CDCl 3 )δ(E isomer)-127.07(dq,J＝83.6,3.8Hz).HRMS(ESI,m/z):calcd for C 12 H 11 NF + [M+H] + :188.0870,found 188.0871.
example 6
General synthesis method a, purified by silica gel column chromatography (PE). White solid (m.p.71-72 ℃); 20.8mg (yield 54%, E/z=66/34); 1 H NMR(400MHz,CDCl 3 )δ(E isomer)7.76-7.68(m,2H),7.35-7.08(m,3H),7.20(s,1H),2.14(dd,J＝3.6,1.6Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ(E isomer)147.1(d,J＝262.9Hz),140.3(d,J＝8.6Hz),139.9,138.3,124.7,124.6,123.3,122.2,120.8(d,J＝8.0Hz),115.9(d,J＝13.8Hz),12.1(d,J＝5.4Hz). 19 F NMR(376MHz,CDCl 3 )δ(E isomer)-129.18(dq,J＝83.6,3.6Hz).HRMS(ESI,m/z):calcd for C 11 H 10 FS + [M+H] + :193.0482,found 193.0483.
example 7
Zn (OAc) was added to a 25mL pressure-resistant tube under an argon atmosphere 2 (3.7mg,0.02 mmol), xantphos (11.6 mg,0.02 mmol), naOAc (16.4 mg,0.2 mmol) and DMSO (2.0 mL), the reaction solution was stirred at room temperature for 30 minutes, and then PhSiH was added to the reaction solution in this order 3 (64.9 mg,0.6 mmol) and 1p (0.2 mmol) of trifluoromethyl olefin, and the reaction tube was sealed and placed in an oil bath at 120℃and stirred for 24 hours. After the reaction, the reaction mixture was quenched with water (2.0 mL), extracted with methylene chloride, dried over anhydrous sodium sulfate, filtered, and the organic solvent was removed under reduced pressure to give a crude product, which was purified by silica gel column chromatography (PE) to give Compound 3p. A colorless oil; nuclear magnetic yield 33%, E/z=77/23; 1 H NMR(400MHz,CDCl 3 )δ(Z isomer)7.43-7.41(m,2H),7.38-7.34(m,2H),7.29-7.27(m,1H),6.70(dt,J＝84.8,1.6Hz,1H),2.21-2.18(m,2H),0.82-0.73(m,1H),0.47-0.43(m,2H),0.08(dt,J＝6.0,4.5Hz,2H). 13 C NMR(151MHz,CD 2 Cl 2 )δ(Zisomer)144.3(d,J＝259.7Hz),135.5,128.1,128.1,127.2,122.,35.5(d,J＝6.3Hz),9.4,4.5. 19 F NMR(376MHz,CDCl 3 )δ(Z isomer)-133.26(dt,J＝84.8,4.2Hz).HRMS(ESI,m/z):calcd for C 12 H 17 NF + [M+NH 4 ] + :194.1340,found 194.1348.
general synthesis method B for Hydrodefluorination (HDF) reaction of geminal difluoro olefin
Zn (OAc) was added to a 25mL pressure-resistant tube under an argon atmosphere 2 (3.7mg,0.02mmol)、PPh 3 (5.3 mg,0.02 mmol) and DMSO (2.0 mL), the reaction solution was stirred at room temperature for 30 minutes, and then Ph was added to the reaction solution in this order 2 SiH 2 (36.8 mg,0.2 mmol) and gem-difluoroolefin 4 (0.2 mmol), the reaction tube was sealed and placed in an oil bath at 50℃and stirred for 24 hours. After the reaction, the reaction solution is quenched by adding water (2.0 mL), extracted by methylene dichloride, dried by anhydrous sodium sulfate, filtered, and the organic solvent is removed under reduced pressure to obtain a crude product, and finally the crude product is purified by silica gel column chromatography to obtain monofluoroolefin products 3a,3m and 5a-5z.
Example 8
Condition optimization experiment
Catalyst cat (10 mmol), ligand L (10 mmol%) and solvent (2.0 mL) were added to a 25mL pressure-resistant tube under argon atmosphere, the reaction was stirred at room temperature for 30 minutes, then silane 2 (0.4 mmol) and gem-difluoroolefin 4a (0.2 mmol) were added sequentially to the reaction, and after the addition, the reaction tube was sealed and placed in an oil bath at T℃and stirred for 24 hours. After the reaction, the reaction solution was quenched with water (2.0 mL), extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and the organic solvent was removed under reduced pressure to obtain a crude product, which was finally purified by silica gel column chromatography to obtain compound 5a.
The results are shown in the following table:
a reaction conditions 4a (0.20 mmol), 2 (0.40 mmol), catalyst cat (10 mmol), ligand L (10 mmol), solvent (2.0 mL), reaction for 24 hours under argon protection, determination of nuclear magnetic resonance yield with benzotrifluoride (0.1 mmol) as internal standard, by 1 HNMR measured the E/Z ratio. b 2a(0.20mmol)。 c 2a(0.20mmol),Zn(OAc) 2 (5mmol％)。 d Under air conditions.
Through a series of condition screening, the final product is Zn (OAc) 2 /PPh 3 Monofluoroolefin compound 5a (entry 17) was successfully synthesized in 84% yield and 95/5E/Z ratio under a catalytic system.
Example 9
The following products were prepared by the general synthetic method B, except for the specific labeling or reaction conditions.
a Reaction conditions 1 (0.20 mmol), ph 2 SiH 2 (0.20mmol),Zn(OAc) 2 (0.02mmol),PPh 3 (0.02 mmol), DMSO (2.0 mL), 50℃under argon for 24 hours, isolation yield and E/Z ratio by 1 HNMR assay. b Ph 2 SiH 2 (0.40mmol),100℃.
Example 10
General synthetic method B, purified by silica gel column chromatography (PE). White solid (m.p. 67-68 ℃); 28.9mg (yield 84%, E/z=95/5); 1 H NMR(400MHz,CDCl 3 )(mixture of isomers)δ(E isomer)7.82-7.77(m,3H),7.65(s,1H),7.49-7.20(m,4H),6.56(dd,J＝19.6,11.2Hz,1H)；(Z isomer)6.74(dd,J＝82.8,5.6Hz,1H),5.78(dd,J＝44.8,5.6Hz,1H). 13 C NMR(101MHz,CDCl 3 )(mixture of isomers)δ150.6(d,J＝259.3Hz),133.7,132.9,130.3(d,J＝11.8Hz),128.6,127.9,126.6,126.1,125.9(d,J＝5.0Hz),123.5,114.3(d,J＝16.3Hz). 19 F NMR(376MHz,CDCl 3 )(mixture of isomers)δ(Zisomer)-121.74(dd,J＝82.8,44.8Hz)；(E isomer)-129.39(dd,J＝83.2,19.6Hz).HRMS(ESI,m/z):calcd for C 12 H 10 F + [M+H] + :173.0761,found 173.0756.
example 11
General synthetic method B, purified by silica gel column chromatography (PE). White solid (m.p.100-101 ℃); 33.7mg (yield 85%, E/z=95/5); 1 H NMR(600MHz,CDCl 3 )(mixture of isomers)δ(E isomer)7.61-7.56(m,4H),7.47-7.45(m,2H),7.38-7.16(m,4H),6.45(dd,J＝19.2,11.4Hz,1H)；(Zisomer)6.70(dd,J＝82.8,5.4Hz,1H),5.68(dd,J＝45.0,5.4Hz,1H). 13 C NMR(151MHz,CDCl 3 )(mixture of isomers)δ150.3(d,J＝259.5Hz),140.7,140.4(d,J＝2.2Hz),131.8(d,J＝12.0Hz),129.0,127.6,127.5,127.0,126.7(d,J＝3.2Hz),113.7(d,J＝16.1Hz). 19 F NMR(376MHz,CDCl 3 )(mixture of isomers)δ(Z isomer)-121.68(dd,J＝82.8,45.0Hz)；(Eisomer)-129.47(dd,J＝83.2,19.2Hz).HRMS(ESI,m/z):calcd for C 14 H 15 FN + [M+NH 4 ] + :216.1183,found 216.1178.
example 12
General synthesis method B, purified by silica gel column chromatography (PE: ea=5:1). White solid (m.p.72-73 ℃); 32.9mg (yield 95%, E/z=95/5); 1 H NMR(600MHz,CDCl 3 )δ(E isomer)8.86(s,1H),8.09-8.02(m,2H),7.63-7.23(m,4H),6.55(dd,J＝19.2,11.4Hz,1H). 13 C NMR(151MHz,CDCl 3 )δ(Eisomer)151.2(d,J＝252.0Hz),150.3,147.9,135.9,131.2(d,J＝12.1Hz),130.1,128.6,127.2,125.4(d,J＝4.5Hz),121.8,113.7(d,J＝16.5Hz). 19 F NMR(376MHz,CDCl 3 )(mixture of isomers)δ(Z isomer)-120.58(dd,J＝82.6,43.8Hz)；(E isomer)-127.48(dd,J＝82.8,18.9Hz).HRMS(ESI,m/z):calcd for C 11 H 9 FN + [M+H] + :174.0714,found 174.0711.
example 13
General synthetic method B, purified by silica gel column chromatography (PE). White solid (m.p.65-66 ℃); 40.1mg (yield 98%, E/z=89/11); 1 H NMR(400MHz,CDCl 3 )(mixture of isomers)δ(E isomer)7.55-7.53(m,2H),7.37-7.33(m,2H),7.28-6.86(m,4H),6.50(dd,J＝17.6,11.2Hz,1H)；(Zisomer)5.93(dd,J＝43.2,5.2Hz,1H). 13 C NMR(101MHz,CDCl 3 )(mixture of isomers)δ149.8(d,J＝262.0Hz),142.8(d,J＝3.4Hz),134.4(d,J＝11.6Hz),134.1,129.1(d,J＝1.8Hz),127.8,127.2(d,J＝6.6Hz),125.8,123.4,108.5(d,J＝20.3Hz). 19 F NMR(376MHz,CDCl 3 )(mixture of isomers)δ(Z isomer)-120.38(dd,J＝81.8,43.2Hz)；(E isomer)-129.04(dd,J＝82.2,17.6Hz).HRMS(ESI,m/z):calcd for C 12 H 10 FS + [M+H] + :205.0482,found 205.0479.
example 14
General synthetic method B, purified by silica gel column chromatography (PE). A colorless oil; 15.9mg (yield 41%, E/z=73/27); 1 H NMR(400MHz,CDCl 3 )(mixture of isomers)δ(E isomer)7.74(d,J＝80.8Hz,1H),7.41-7.33(m,5H),4.27(q,J＝7.2Hz,2H),1.31(t,J＝7.2Hz,3H)；(Zisomer)6.99(d,J＝79.6Hz,1H). 13 C NMR(101MHz,CDCl 3 )(mixture of isomers)δ166.1(d,J＝16.4Hz),158.0(d,J＝282.0Hz),130.0(d,J＝2.8Hz),128.4,128.2,119.8(d,J＝7.3Hz),61.3,14.3. 19 F NMR(376MHz,CDCl 3 )(mixture of isomers)δ(Zisomer)-110.62(d,J＝79.6Hz)；(E isomer)-114.70(d,J＝80.8Hz).HRMS(ESI,m/z):calcd for C 11 H 12 FO 2 + [M+H] + :195.0816,found 195.0817.
general synthesis method C for dehydrofluorination (HDF) reaction of polyfluoroaromatic hydrocarbon
Zn (OAc) was added to a 25mL pressure-resistant tube under an argon atmosphere 2 (3.7mg,0.02mmol)、PPh 3 (5.3 mg,0.02 mmol) and DMSO (2.0 mL), the reaction solution was stirred at room temperature for 30 minutes, and then Ph was added to the reaction solution in this order 2 SiH 2 (36.8 mg,0.2 mmol) and polyfluoroaromatic hydrocarbon 6 (0.2 mmol), and the reaction tube was sealed and placed in an oil bath at 50℃and stirred for 24 hours. After the reaction, the reaction mixture was quenched with water (2.0 mL), extracted with methylene chloride, dried over anhydrous sodium sulfate, filtered, and the organic solvent was removed under reduced pressure to give a crude product, which was purified by silica gel column chromatography to give compounds 7a,7b.
Example 15
General synthetic method C. After the reaction was completed, 0.1mmol of trifluoromethylbenzene was added as an internal standard to the sealed tube to give a crude product 19 F nuclear magnetic yield 76%. 19 F NMR(376MHz,DMSO-d6)δ-55.05--55.19(m,3F),-136.29-136.43(m,2F),-141.15--141.32(m,2F).HRMS(ESI,m/z):calcd for C 7 HF 7 Na + [M+Na] + :240.9859,found 240.9870.
Example 16
General synthesis method C, purification by silica gel column chromatography (PE). White solid (m.p. 75-76 ℃); 41.7mg (yield 66%); 1 H NMR(400MHz,CDCl 3 )δ7.35–7.27(m,1H). 19 F NMR(376MHz,CDCl 3 )δ-137.38–-137.49(m,4F),-138.16–-138.28(m,2F),-149.92–-150.34(m,1F),-160.47–-160.60(m,2F).HRMS(ESI,m/z):calcd for C 12 HF 9 K + [M+K] + :354.9566,found 354.9571.
EXAMPLE 17 Scale-up
Zn (OAc) was added to a 100mL pressure-resistant tube under an argon atmosphere 2 (36.7 mg,0.2 mmol), xantphos (115.7 mg,0.2 mmol) and DMSO (20.0 mL), the reaction solution was stirred at room temperature for 30 minutes, and then successively adding Ph to the reaction solution 2 SiH 2 (1105.9 mg,6 mmol) and 1m (496.2 mg,2 mmol) of trifluoromethyl olefin, after the addition, the reaction tube was sealed and placed in an oil bath at 120℃and stirred for 24 hours. After the reaction is finished, the reaction solution is quenched by adding water (20 mL), extracted by methylene dichloride, dried by anhydrous sodium sulfate, filtered and decompressed to remove the organic solvent to obtain a crude productFinally purification by silica gel column chromatography (PE) gave the monofluoroolefin product 3m (313.8 mg, yield 74%, E/z=87/13). 1 H NMR(400MHz,CDCl 3 )(mixture of isomers)δ(Eisomer)7.63–7.53(m,4H),7.46-7.44(m,2H),7.41-7.30(m,3H),6.98(dq,J＝84.9,1.5Hz,1H),2.09(dd,J＝3.8,1.5Hz,3H)；(Zisomer)6.71(dq,J＝84.5,1.8Hz,1H),1.96(dd,J＝4.9,1.6Hz,3H). 13 C NMR(101MHz,CDCl 3 )(mixture of isomers)δ146.2(d,J＝258.6Hz),140.8,140.4,136.7(d,J＝8.8Hz),129.0,127.5,127.4,127.1,126.4(d,J＝3.0Hz),119.8(d,J＝10.1Hz),12.3(d,J＝5.9Hz). 19 F NMR(376MHz,CDCl 3 )(mixture of isomers)δ(Zisomer)-128.05–-128.32(m)；(E isomer)-130.75–-131.01(m).
EXAMPLE 18 derivatization reaction
Monofluoroolefin compound 5a (34.4 mg,0.2 mmol) and NiCl were reacted under argon atmosphere 2 (dppe) (4.2 mg,0.008 mmol) and 0.4mL dry THF were added to a 25mL pressure-resistant tube and mixed well. Then, a THF solution (0.8 mmol) of the Grignard reagent was added dropwise to the reaction solution, and the reaction solution was stirred at room temperature for 2 hours. After the completion of the reaction, a saturated aqueous ammonium chloride solution (2.0 mL) was quenched, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the organic solvent was removed under reduced pressure to give a crude product, which was finally purified by silica gel column chromatography (PE) to give compound 8 (40.1 mg, yield 87%). 1 H NMR(400MHz,CDCl 3 )δ7.85-7.80(m,4H),7.75-7.73(m,1H),7.57-7.55(m,2H),7.49-7.42(m,2H),7.39-7.37(m,2H),7.30-7.20(m,3H). 13 C NMR(101MHz,CDCl 3 )δ137.5,135.0,133.9,133.2,129.2,128.9,128.9,128.5,128.2,127.8,127.8,126.8,126.7,126.5,126.0,123.7.HRMS(ESI,m/z):calcd for C 18 H 15 + [M+H] + :231.1168,found 231.1169.
EXAMPLE 19 derivatization reaction
Pd (OAc) was taken under argon atmosphere 2 (2.3 mg,0.01 mmol), neocuproine (3.1 mg,0.015 mmol), N-fluoro bis-benzenesulfonamide (158 mg,0.5 mmol) and 1, 4-dioxane (1.0 mL) were added to a 25mL pressure-resistant tube and mixed well, then monofluoroolefin compound 5a (34.4 mg,0.2 mmol) was added, and after the addition, the reaction tube was sealed and placed in an oil bath at 50℃for stirring for 20 hours. After the completion of the reaction, celite filtration, washing with ethyl acetate, and purification of the resulting filtrate by silica gel column chromatography (PE: ea=5:1) after removal of the organic solvent under reduced pressure gave compound 9 (60.4 mg, yield 62%). 1 H NMR(400MHz,CDCl 3 )δ7.89-6.87(m,18H),5.93(dt,J＝10.4,8.0Hz,1H). 13 C NMR(101MHz,CDCl 3 )δ139.6,133.9,133.2,132.8,128.9,128.8,128.6,128.5,127.6,127.3,126.8,126.4,114.5(dd,J＝246.8,241.8Hz),64.0(dd,J＝35.9,23.4Hz). 19 F NMR(376MHz,CDCl 3 )δ-116.40(ddd,J＝293.0,57.1,10.2Hz,1F),-124.87(ddd,J＝293.0,56.4,8.3Hz,1F).HRMS(ESI,m/z):calcd for C 24 H 20 F 2 NO 4 S 2 + [M+H] + :488.0796,found 488.0773.
EXAMPLE 20 derivatization reaction
Zn (OAc) was added to a 25mL pressure-resistant tube under an argon atmosphere 2 (3.7mg,0.02mmol)、PPh 3 (5.3 mg,0.02 mmol) and DMSO (2.0 mL), the reaction solution was stirred at room temperature for 30 minutes, and then Ph was added to the reaction solution in this order 2 SiH 2 (73.6 mg,0.4 mmol) and gem-difluoroolefin 10 (135.7 mg,0.2 mmol), after which the reaction tube was sealed and placed in an oil bath at a temperature of 100℃and stirred for 24 hours. After the reaction, the reaction mixture was quenched with water (2.0 mL), extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and the organic solvent was removed under reduced pressure to give a crude product, which was finally purified by silica gel column chromatography (PE: ea=10:1) to give monofluoroolefin product 11 (46.2 mg, yield 35%, E/z=90/10).
A gem-difluoroolefin 10, 1 H NMR(400MHz,CDCl 3 )δ7.38-7.20(m,22H),7.06-7.04(m,2H),5.51(d,J＝7.9Hz,1H),5.20(dd,J＝26.4,3.8Hz,1H),4.95-4.29(m,8H),4.22(m,1H),4.17(t,J＝2.6Hz,1H),3.85-3.63(m,2H),3.54(m,2H). 13 C NMR(101MHz,CDCl 3 )δ156.6(t,J＝2.3Hz),156.0(dd,J＝297.1,286.9Hz),139.0,138.6,138.4,137.9,128.8(dd,J＝6.2,3.4Hz),128.5,128.5,128.4,128.3,128.1,127.9,127.9,127.8,127.8,127.8,127.6,127.6,124.4(t,J＝6.3Hz),117.2,99.3,81.7(dd,J＝29.3,14.2Hz),78.8,75.6,74.8,74.7,73.6,73.2,72.9,71.7,69.2. 19 F NMR(376MHz,CDCl 3 )δ-84.07(dd,J＝35.4,26.2Hz,1F),-85.86(dd,J＝36.0,4.1Hz,1F).HRMS(ESI,m/z):calcd for C 42 H 41 F 2 O 6 + [M+H] + :679.2866,found 679.2857.
the monofluoro product 11 is produced in a reaction, 1 H NMR(400MHz,CDCl 3 )(mixture of isomers)δ(Eisomer)7.38-7.20(m,20H),7.19-6.96(m,5H),6.35(dd,J＝19.2,11.2Hz,1H),5.49(d,J＝7.9Hz,1H),4.94-4.36(m,8H),4.22(m,1H),4.18(t,J＝2.6Hz,1H),3.89-3.63(m,2H),3.61-3.49(m,2H)；(Zisomer)6.60(dd,J＝82.8,5.2Hz,1H). 13 C NMR(151MHz,CDCl 3 )(mixture of isomers)δ157.2,149.4(d,J＝256.8Hz),139.0,138.6,138.5,137.9,128.6,128.5,128.4,128.3,128.1,128.0,127.9,127.9,127.8,127.8,127.6,127.6,127.3(d,J＝3.1Hz),126.8(d,J＝12.1Hz),117.3,113.5(d,J＝15.6Hz),99.3,78.8,75.6,74.9,74.7,73.6,73.2,72.9,71.8,69.3. 19 F NMR(376MHz,CDCl 3 )(mixture of isomers)δ(Z isomer)-124.68(dd,J＝82.8,45.7Hz)；(E isomer)-132.03(dd,J＝84.0,19.2Hz).HRMS(ESI,m/z):calcd for C 42 H 42 FO 6 + [M+H] + :661.2960,found679.2955.
the foregoing is merely a preferred embodiment of the invention and it is not intended that the invention be limited to this description. It will be apparent to those skilled in the art that several simple deductions and substitutions can be made without departing from the spirit of the invention, and any modifications, equivalent substitutions, improvements, etc. made by these are intended to be included in the scope of the present invention.
Claims (10)
1. A method for synthesizing monofluoroolefins, comprising the steps of: in the method A, trifluoromethyl substituted olefin 1 and silane 2 react in an organic solvent under heating in the presence of a ligand by taking zinc acetate as a catalyst to obtain trisubstituted (E) -monofluoroolefin compounds 3; the reaction equation is expressed as:
wherein: r is selected from H or cyclopropane; ar is selected from substituted or unsubstituted phenyl, naphthyl, heteroaryl, substituted or unsubstituted biaryl; silane 2 is selected from diphenylsilane or phenylsilane; in the method B, the gem-difluoro olefin 4 and diphenyl silane 2a react in an organic solvent under heating in the presence of a ligand by taking zinc acetate as a catalyst to obtain a di/tri-substituted (E) -difluoro olefin compound 5; the reaction equation is expressed as:
wherein: r is R 1 Selected from hydrogen, methyl, propyl, phenyl, ethyl formate; ar (Ar) 1 Selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted heteroaryl, and substituted or unsubstituted biaryl.
2. The method for synthesizing monofluoroolefins according to claim 1, characterized in that: the substitution in the substituted or unsubstituted phenyl refers to substitution at any position of the phenyl by one or more of the following groups, the same or different substituents: halogen, methyl, trifluoromethoxy, t-butyl formate, diphenylamino, methoxy, t-butyl, phenyl, phenoxy, methyl formate, neopentyl; the substitution in the substituted or unsubstituted naphthyl refers to substitution at any position of the naphthyl by one or more of the following groups, the same or different substituents: methoxy, benzyloxy, allyloxy; the heteroaryl is selected from quinolinyl, indolyl, benzofuranyl, benzothienyl; the substituted heteroaryl is selected from phenyl substituted thienyl, chlorobenzene substituted thienyl, fluorobenzene substituted furyl; the substitution in the substituted or unsubstituted biaryl refers to substitution at any position of the phenyl group with one or more of the following groups, the same or different substituents: methyl, methoxy, methyl formate, halogen, trifluoromethyl.
3. The method for synthesizing monofluoroolefins according to claim 1, characterized in that: the organic solvent is selected from DMSO, DMF, DCE, THF, dimethylacetamide, ethylene glycol dimethyl ether, toluene, methanol, tert-butyl methyl ether or 1, 4-dioxane.
4. The method for synthesizing monofluoroolefins according to claim 1, wherein the ligand is a compound represented by the following structure:
5. the method for synthesizing monofluoroolefins according to claim 4, wherein: in method a, the ligand is selected from xanaphos; in Process B, the ligand is selected from PPh 3 。
6. The method for synthesizing monofluoroolefins according to claim 1, characterized in that: the molar ratio of the compound 1 to the compound 2 is 1:3; the mol ratio of the compound 4 to the compound 2a is 1:1-2; the molar ratio of the compound 1 or 4, zinc acetate and the ligand is 1:0.1-0.2:0.1-0.2.
7. The method for synthesizing monofluoroolefins according to claim 1, characterized in that: the heating reaction temperature is 50-130 ℃.
8. The method for synthesizing monofluoroolefins according to claim 1, characterized in that: the reaction is carried out under the protection of inert gas.
9. A method for synthesizing tetrafluoroaryl compound 7, comprising the steps of: the preparation method comprises the steps of (1) heating polyfluoroaromatic hydrocarbon 6 and diphenyl silane 2a in a DMSO solvent by taking zinc acetate as a catalyst and triphenylphosphine as a ligand to react to obtain hydrodefluorination compound 7; the reaction equation is expressed as:
wherein R is 2 Selected from trifluoromethyl or pentafluorophenyl.
10. The method for synthesizing tetrafluoroaryl compound 7 as claimed in claim 9, wherein: the molar ratio of the compound 6 to the compound 2a is 1:1; the mol ratio of the compound 6 to the zinc acetate to the triphenylphosphine is 1:0.1:0.1; the heating reaction temperature is 50-60 ℃; the reaction is carried out under the protection of inert gas.
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