CN114773161A - (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-alcohol derivative and synthetic method thereof - Google Patents
(4E) -1-fluoro-2, 5-diaryl-4-pentene-2-alcohol derivative and synthetic method thereof Download PDFInfo
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- CN114773161A CN114773161A CN202210224104.5A CN202210224104A CN114773161A CN 114773161 A CN114773161 A CN 114773161A CN 202210224104 A CN202210224104 A CN 202210224104A CN 114773161 A CN114773161 A CN 114773161A
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- 238000010189 synthetic method Methods 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 79
- 238000000034 method Methods 0.000 claims abstract description 46
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000001301 oxygen Substances 0.000 claims abstract description 38
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 38
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 15
- 239000011737 fluorine Substances 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 150000001543 aryl boronic acids Chemical class 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 5
- 239000000463 material Substances 0.000 claims abstract description 5
- 239000000575 pesticide Substances 0.000 claims abstract description 4
- 230000009471 action Effects 0.000 claims abstract description 3
- 239000012429 reaction media Substances 0.000 claims abstract description 3
- 229940079593 drug Drugs 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 288
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 68
- 238000004440 column chromatography Methods 0.000 claims description 66
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 63
- -1 o-methylphenyl Chemical group 0.000 claims description 45
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 44
- 230000002194 synthesizing effect Effects 0.000 claims description 39
- 238000000746 purification Methods 0.000 claims description 37
- 239000003208 petroleum Substances 0.000 claims description 34
- 239000000243 solution Substances 0.000 claims description 33
- 239000003480 eluent Substances 0.000 claims description 32
- 239000002904 solvent Substances 0.000 claims description 32
- 238000001816 cooling Methods 0.000 claims description 31
- 238000002390 rotary evaporation Methods 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 239000012266 salt solution Substances 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 8
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- 229910052763 palladium Inorganic materials 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- 239000004327 boric acid Substances 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- HHXBZEIOUIMZET-UHFFFAOYSA-N (2,3-dichlorophenyl)-phenylphosphane Chemical compound ClC1=CC=CC(PC=2C=CC=CC=2)=C1Cl HHXBZEIOUIMZET-UHFFFAOYSA-N 0.000 claims 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 abstract description 13
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 238000001308 synthesis method Methods 0.000 abstract description 6
- 239000003513 alkali Substances 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract description 2
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- 239000000758 substrate Substances 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 101
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 94
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 40
- 238000010438 heat treatment Methods 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- 238000000926 separation method Methods 0.000 description 30
- 238000003756 stirring Methods 0.000 description 30
- BETQFQBXSCJWBJ-UHFFFAOYSA-N 1,1,1-trifluoro-2-phenylpent-4-en-2-ol Chemical compound C=CCC(O)(C(F)(F)F)C1=CC=CC=C1 BETQFQBXSCJWBJ-UHFFFAOYSA-N 0.000 description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 239000011780 sodium chloride Substances 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 238000004293 19F NMR spectroscopy Methods 0.000 description 16
- 238000012512 characterization method Methods 0.000 description 16
- 150000001336 alkenes Chemical class 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 1
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 1
- DJGHSJBYKIQHIK-UHFFFAOYSA-N (3,5-dimethylphenyl)boronic acid Chemical compound CC1=CC(C)=CC(B(O)O)=C1 DJGHSJBYKIQHIK-UHFFFAOYSA-N 0.000 description 1
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 1
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
- XPEIJWZLPWNNOK-UHFFFAOYSA-N (4-phenylphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=CC=CC=C1 XPEIJWZLPWNNOK-UHFFFAOYSA-N 0.000 description 1
- GUNWYWZXLBPTEV-UHFFFAOYSA-N ClC1=CC=C(C=C1)C(C(F)(F)F)(CC=C)O Chemical compound ClC1=CC=C(C=C1)C(C(F)(F)F)(CC=C)O GUNWYWZXLBPTEV-UHFFFAOYSA-N 0.000 description 1
- VMRQNVGMDATSKR-UHFFFAOYSA-N FC(C(CC=C)(O)C1=CC=C(C=C1)C)(F)F Chemical compound FC(C(CC=C)(O)C1=CC=C(C=C1)C)(F)F VMRQNVGMDATSKR-UHFFFAOYSA-N 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/40—Halogenated unsaturated alcohols
- C07C33/46—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts
- C07C33/48—Halogenated unsaturated alcohols containing only six-membered aromatic rings as cyclic parts with unsaturation outside the aromatic rings
- C07C33/483—Monocyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/19—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to acyclic carbon atoms of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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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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- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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Abstract
The invention belongs to the technical field of preparation of fluorine-containing compounds, and discloses a (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-alcohol derivative and a synthesis method thereof. The (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative is shown in a formula I. The method comprises the following steps: taking an organic solvent as a reaction medium, and reacting the 1-fluoro-2-aryl-4-pentene-2-ol derivative with arylboronic acid under the action of a catalyst and oxygen to obtain (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives. The method has high efficiency and simple and mild conditions, does not need to add ligand and alkali, and can obtain a target product only by catalysis of catalyst/oxygen; the reaction has high adaptability to functional groups, wide adaptability to substrates and high product yield, can be produced and synthesized on a gram-scale, and the obtained product has wide application in the fields of pesticides, medicines and materials.
Description
Technical Field
The invention belongs to the field of fluorine-containing compounds, and particularly relates to a (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-alcohol derivative and a synthesis method thereof.
Background
Fluorine has large electronegativity and small radius, and the introduction of fluorine atoms or fluorine-containing groups into organic molecules can effectively change the physicochemical properties of the organic molecules, so that the fluorine-containing compounds have very wide application in the fields of biological medicine, pesticide, material science and the like. It was investigated that the fluorine-containing compounds in all agricultural chemicals accounted for about 30% and the fluorine-containing compounds in the pharmaceuticals accounted for about 20%. Fluorinated materials have been widely used in liquid crystal displays. In addition, fluorine-labeled molecular probes can also be used for the diagnosis of diseases. Therefore, in order to satisfy the urgent needs of research and search for fluorine-containing compounds and the increasing kinds and amounts of fluorine-containing compounds, efficient synthesis of fluorine-containing compounds is one of the problems that chemists have urgently needed to solve.
The cross-coupling reaction among molecules is one of the important methods for constructing C-C bond, and the Heck reaction for obtaining the chemical prize of Nobel in 2010 is the construction of C (sp)2)-C(sp2) A key. However, this method is generally limited to activated electron deficient olefins, but coupling reactions are difficult to occur with unactivated olefins. Therefore, developing a method for efficiently reacting an unactivated olefin with an aryl group is still a challenging research topic.
Disclosure of Invention
In view of the above disadvantages and shortcomings of the prior art, the present invention is primarily directed to a method for efficiently synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives.
Another objective of the invention is to provide a method for synthesizing the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative.
The purpose of the invention is realized by the following technical scheme.
A (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative having the structure:
wherein Ar is1Is phenyl, p-methylphenyl, o-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, 3, 4-dimethoxyphenyl, p-fluorophenyl, o-fluorophenyl, p-chlorophenyl, o-chlorophenyl, 3, 5-dichlorophenyl, p-bromophenyl, o-bromophenyl or p-trifluoromethylphenyl.
Ar2Is phenyl, p-tolyl, o-tolyl, p-methoxyphenyl, o-methoxyphenyl, p-thiomethylphenyl (p-methylthiophenyl), p-tert-butylphenyl, p-fluorophenyl, m-fluorophenyl, p-chlorophenyl, p-bromophenyl, o-bromophenyl, 3, 5-dimethylphenyl, p-methylsulfonylphenyl, p-phenylphenyl or 2-naphthyl.
R1Is hydrogen, methyl or ethyl.
R2Is hydrogen or fluorine.
R3Is hydrogen, methyl or ethyl
R4Is hydrogen or methyl.
The synthesis method of the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative comprises the following steps:
taking an organic solvent as a reaction medium, reacting the 1-fluoro-2-aryl-4-pentene-2-alcohol derivative with arylboronic acid under the action of a catalyst and oxygen, and separating and purifying a product after the reaction is finished to obtain the (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-alcohol derivative.
The 1-fluoro-2-aryl-4-penten-2-ol derivative is
Wherein Ar is1Is phenyl, p-methylphenyl, o-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, 3, 4-dimethoxyphenyl, p-fluorophenyl, o-fluorophenyl, p-chlorophenyl, o-chlorophenyl, 3, 5-dichlorophenyl, p-bromophenyl, o-bromophenyl or p-trifluoromethylphenyl.
The aryl boric acid is Ar2B(OH)2Wherein Ar is2Is phenyl, p-tolyl, o-tolyl, p-methoxyphenyl, o-methoxyphenyl, p-thiomethylphenyl (p-methylthiophenyl), p-tert-butylphenyl, p-fluorophenyl, m-fluorophenyl, p-chlorophenyl, p-bromophenyl, o-bromophenyl, 3, 5-dimethylphenyl, p-methylsulfonylphenyl, p-phenylphenyl or 2-naphthyl.
R1Is hydrogen, methyl or ethyl.
R2Is hydrogen or fluorine.
R3Is hydrogen, methyl or ethyl.
R4Is hydrogen or methyl.
The molar ratio of the 1-fluoro-2-aryl-4-penten-2-ol derivative to the arylboronic acid is 1:1 to 1:4, preferably 1: (2-4), more preferably 1 (2.5-3.5), still more preferably 1: 3.
the catalyst is one or more of palladium acetate, palladium iodide and tetrakis (triphenylphosphine) palladium, and is further preferably tetrakis (triphenylphosphine) palladium.
The molar ratio of the catalyst to the 1-fluoro-2-aryl-4-penten-2-ol derivative is 1: (5-100), preferably 1: 20.
The organic solvent is more than one of N, N-dimethylformamide, dimethyl sulfoxide, toluene, nitromethane and tetrahydrofuran, and is preferably a mixed solvent of N, N-dimethylformamide and dimethyl sulfoxide;
the volume ratio of the N, N-dimethylformamide to the dimethyl sulfoxide is 1: 1.
The reaction is carried out in oxygen atmosphere, the reaction temperature is 40-110 ℃, and the reaction time is 3-16 h. Preferably, the reaction temperature is 70-100 ℃, further preferably 80-95 ℃, and the reaction time is 10-16 h.
The subsequent treatment is that after the reaction is finished, the reaction solution is cooled to room temperature, the salt solution or water and the organic solvent are added to extract the reaction solution, the organic layer is decompressed and rotary evaporated to remove the solvent, a crude product is obtained, and the (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-ol derivative is obtained through column chromatography purification.
In the subsequent treatment, the organic solvent is ethyl acetate or dichloromethane.
The column chromatography purification refers to the purification by using petroleum ether: and the mixed solvent of ethyl acetate is eluent for column chromatography purification. Petroleum ether: volume ratio of ethyl acetate: (20-500): 1.
The reaction equation involved in the method of the invention:
compared with the prior art, the invention has the following advantages and beneficial effects:
(1) the synthesis method is efficient, and the used raw materials are easy to obtain; the reaction has good adaptability to functional groups, wide adaptability to substrates and high product yield;
(2) the synthesis method is efficient, simple and mild in conditions, and can obtain a target product only by catalysis of catalyst/oxygen without adding ligand and alkali;
(3) the synthesis method can be used for scale-up to gram-scale production, is simple and safe to operate, has mild reaction conditions, and has good industrial application prospect;
(4) the product obtained by the invention has wide application in the fields of pesticide, medicine and material.
Drawings
FIG. 1 shows the products obtained in examples 1 to 151H NMR spectrum;
FIG. 2 shows the products obtained in examples 1 to 1513C NMR spectrum;
FIG. 3 shows the results of examples 1 to 1519F, NMR spectrum;
FIG. 4 is a single crystal structural diagram of the product obtained in example 25.
Detailed Description
The present invention will be described in further detail with reference to specific examples, but the embodiments of the present invention are not limited thereto.
Example 1:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a reaction vessel, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were charged, an oxygen balloon was fitted over the reaction vessel (oxygen was introduced), and the reaction system was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding salt solution and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a volume ratio of 100: 1: ethyl acetate mixture; the product yield was 95%.
Example 2:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-pentene-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of palladium acetate and 2 ml of N, N-dimethylformamide are added into a spiral graduated tube provided with magnetons, an oxygen balloon is sleeved on the graduated tube, and the reaction system is stirred and reacts for 12 hours at 90 ℃. Stopping heating and stirring, cooling to room temperature, adding saline water and ethyl acetate, extracting the reaction solution, performing reduced pressure rotary evaporation on the ethyl acetate, removing the solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 46%.
Example 3:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline water and ethyl acetate, extracting the reaction solution, performing reduced pressure rotary evaporation on the ethyl acetate, removing the solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of the column chromatography eluent is petroleum ether with the volume ratio of 100: 1: ethyl acetate mixture; the product yield was 77%.
Example 4:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of palladium iodide, and 2 ml of N, N-dimethylformamide were added, and an oxygen balloon was fitted over the graduated tube, and the reaction system was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 23%.
Example 5:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of dimethyl sulfoxide are added into a spiral graduated tube provided with magnetons, an oxygen balloon is sleeved on the graduated tube, and the reaction system is stirred and reacts for 12 hours at the temperature of 90 ℃. Stopping heating and stirring, cooling to room temperature, adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 79%.
Example 6:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of toluene were added, an oxygen balloon was fitted over the graduated tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 51%.
Example 7:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of nitromethane are added into a spiral graduated tube provided with magnetons, an oxygen balloon is sleeved on the graduated tube, and the reaction system is stirred and reacted for 12 hours at 90 ℃. Stopping heating and stirring, cooling to room temperature, adding salt solution and ethyl acetate to extract a reaction solution, carrying out reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and carrying out column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a ratio of 100: 1: ethyl acetate mixture; the product yield was 50%.
Example 8:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide are added into a spiral graduated tube provided with magnetons, an oxygen balloon is sleeved on the graduated tube, and the reaction system is stirred and reacts for 12 hours at the temperature of 110 ℃. Stopping heating and stirring, cooling to room temperature, adding salt solution and ethyl acetate to extract a reaction solution, carrying out reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and carrying out column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a ratio of 100: 1: ethyl acetate mixture; the product yield was 56%.
Example 9:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 70 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, adding salt solution and ethyl acetate to extract a reaction solution, carrying out reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and carrying out column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a ratio of 100: 1: ethyl acetate mixture; the product yield was 74%.
Example 10:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide are added into a spiral graduated tube provided with magnetons, an oxygen balloon is sleeved on the graduated tube, and the reaction system is stirred and reacts for 12 hours at the temperature of 50 ℃. Stopping heating and stirring, cooling to room temperature, adding salt solution and ethyl acetate to extract a reaction solution, carrying out reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and carrying out column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a ratio of 100: 1: ethyl acetate mixture; the product yield was 33%.
Example 11:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.3 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide are added into a spiral graduated tube provided with magnetons, an oxygen balloon is sleeved on the graduated tube, and the reaction system is stirred and reacts for 12 hours at 70 ℃. Stopping heating and stirring, cooling to room temperature, adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 15%.
Example 12:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide are added into a spiral graduated tube provided with magnetons, an oxygen balloon is sleeved on the graduated tube, and the reaction system is stirred and reacts for 12 hours at 70 ℃. Stopping heating and stirring, cooling to room temperature, adding salt solution and ethyl acetate to extract a reaction solution, carrying out reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and carrying out column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a ratio of 100: 1: ethyl acetate mixture; the product yield was 66%.
Example 13:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.8 mmol of phenylboronic acid, 0.02 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 70 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 64%.
Example 14:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction system was stirred at 70 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, adding salt solution and ethyl acetate to extract a reaction solution, carrying out reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and carrying out column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a ratio of 100: 1: ethyl acetate mixture; the product yield was 89%.
Example 15:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.4 mmol of phenylboronic acid, 0.04 mmol of tetrakis (triphenylphosphine) palladium and 2 ml of N, N-dimethylformamide are added into a spiral graduated tube provided with magnetons, an oxygen balloon is sleeved on the graduated tube, and the reaction system is stirred and reacts for 12 hours at 70 ℃. Stopping heating and stirring, cooling to room temperature, adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 54%.
Examples 1 to 15 of the obtained products1H NMR，13C NMR，19The F NMR patterns are respectively shown in FIG. 1, FIG. 2 and FIG. 3, and the structural characterization data are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.62(d,J＝8.0,2H),7.43-7.31(m,3H),7.28-7.15(m,5H),6.72(s,1H),6.50(d,J＝16.0Hz,1H),5.96(dt,J＝16.0,8.0Hz,1H),3.07(ddd,J＝80.0,12.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δppm 137.8,137.3,133.9,129.0,128.5,128.4,127.7,127.4,126.4(q,JC-F＝262.6Hz),126.2,123.5,75.9(q,JC-F＝26.3Hz),38.1.
19F NMR(376MHz,DMSO-d6)δppm-78.23.
the structures of the products obtained in examples 1 to 15 were deduced from the above data:
example 16:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-methylbenzeneboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, adding salt solution and ethyl acetate to extract a reaction solution, carrying out reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and carrying out column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a ratio of 100: 1: ethyl acetate mixture; the product yield was 94%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.41-7.30(m,3H),7.10-7.04(m,4H),6.68(s,1H),6.43(d,J＝16.0Hz,1H),5.88(dt,J＝16.0,8.0Hz,1H),3.04(ddd,J＝80.0,16.0,8.0Hz,2H),2.22(s,3H).
13C NMR(101MHz,DMSO-d6)δppm 137.3,136.5,134.1,133.3,129.1,128.0,127.9,126.9,125.9(q,JC-F＝288.9Hz)125.7,121.9,76.0(q,JC-F＝27.3Hz),37.7,20.7.
19F NMR(376MHz,DMSO-d6)δppm-78.23.
the structure of the product obtained in this example was deduced from the above data:
example 17:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of o-tolylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the graduated tube, and the reaction system was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 90%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.62(d,J＝8.0Hz,2H),7.42-7.31(m,3H),7.14-7.04(m,4H),6.71(s,1H),6.65(d,J＝16.0Hz,1H),5.78(dt,J＝16.0,8.0Hz,1H),3.08(ddd,J＝84.0,16.0,8.0Hz,2H),2.13(s,3H).
13C NMR(101MHz,DMSO-d6)δppm 137.3,136.1,134.5,131.8,123.0,128.0,127.9,127.1,127.0,126.0(q,JC-F＝288.9Hz),126.0,125.1,124.3,76.0(q,JC-F＝27.3Hz),37.9,19.2.
19F NMR(376MHz,DMSO-d6)δppm-78.27.
the structure of the product obtained in this example was deduced from the above data:
example 18:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-methoxyphenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the graduated tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 95%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.42-7.30(m,3H),7.13(d,J＝8.0Hz,2H),6.81(d,J＝8.0Hz,2H),6.66(s,1H),6.41(d,J＝16.0Hz,1H),5.78(dt,J＝16.0,8.0Hz,1H),3.70(s,3H),3.03(ddd,J＝80.0,12.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δppm 159.1,137.9,133.4,130.0,128.5,128.4,127.4,127.4,126.4(q,JC-F＝288.9Hz),121.0,114.4,76.4(q,JC-F＝27.3Hz),55.5,38.2.
19F NMR(376MHz,DMSO-d6)δppm-78.20.
the structure of the product obtained in this example was deduced from the above data:
example 19:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of o-methoxyphenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the graduated tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 93%.
The structural characterization data of the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.61(d,J＝8.0Hz,2H),7.41-7.31(m,3H),7.18-7.13(m,2H),6.92(d,J＝8.0Hz,1H),6.82(t,J＝8.0Hz,1H),6.70(d,J＝16.0Hz,1H),6.68(s,1H)5.91(dt,J＝16.0,8.0Hz,1H),3.72(s,3H),3.06(ddd,J＝80.0,12.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δppm 155.9,137.4,128.4,128.0,127.9,126.9,126.0(q,JC-F＝287.9Hz),125.9,125.5,123.4,120.5,111.3,76.0(q,JC-F＝26.3Hz),55.3,38.1.
19F NMR(376MHz,DMSO-d6)δppm-78.14.
the structure of the product obtained in this example was deduced from the above data:
example 20:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-thiomethylphenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the graduated tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 56%.
The structural characterization data of the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.59(d,J＝7.6Hz,2H),7.41-7.31(m,3H),7.14(s,4H),6.69(s,1H),6.43(d,J＝16.0Hz,1H),5.90(dt,J＝16.0,8.0Hz,1H),3.04(ddd,J＝80.0,16.0,8.0Hz,2H),2.42(s,3H).
13C NMR(101MHz,DMSO-d6)δppm 137.8,137.5,134.1,133.3,128.5,128.4,127.4,126.8,126.6,126.4(q,JC-F＝287.9Hz),76.4(q,JC-F＝26.3Hz),38.2,15.2.
19F NMR(376MHz,DMSO-d6)δppm-78.21.
the structure of the product obtained in this example was deduced from the above data:
example 21:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-tert-butylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was put on the graduated tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 94%.
The structural characterization data of the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.40-7.24(m,6H),7.12(d,J＝8.4Hz,2H),6.69(s,1H),6.44(d,J＝16.0Hz,1H),5.90(dt,J＝16.0,8.0Hz,1H),3.05(ddd,J＝76.0,16.0,8.0Hz,2H),1.22(s,9H).
13C NMR(101MHz,DMSO-d6)δppm 150.2,137.8,134.6,133.7,128.5,128.4,127.4,126.3(q,JC-F＝287.9Hz),126.0,125.7,122.6,76.4(q,JC-F＝27.3Hz),38.2,34.6,31.5.
19F NMR(376MHz,DMSO-d6)δppm-78.22.
the structure of the product obtained in this example was deduced from the above data:
example 22:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-chlorobenzeneboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the graduated tube, and the reaction system was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 80%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.41-7.28(m,5H),7.21(d,J＝8.0Hz,2H),6.72(s,1H),6.48(d,J＝16.0Hz,1H),5.96(dt,J＝16.0,8.0Hz,1H),3.06(ddd,J＝84.0,16.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δppm 137.7,136.2,132.7,132.1,129.0,128.6,128.5,127.9,127.4,126.4(q,JC-F＝287.9Hz),124.6,76.5(q,JC-F＝26.3Hz),38.1.
19F NMR(376MHz,DMSO-d6)δppm-78.25.
the structure of the product obtained in this example was deduced from the above data:
example 23:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-bromophenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the graduated tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 86%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,Chloroform-d)δppm 7.59(d,J＝8.0Hz,2H),7.45-7.30(m,5H),7.18-7.13(m,2H),6.72(s,1H),6.46(d,J＝16.0Hz,1H),5.97(dt,J＝16.0,8.0Hz,1H),3.05(ddd,J＝84.0,16.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δppm 136.4,135.2,131.5,130.6,127.3,127.2,127.0,126.4(q,JC-F＝295.9Hz),126.1,123.4,119.3,75.1(q,JC-F＝27.3Hz),36.9.
19F NMR(376MHz,DMSO-d6)δppm-78.27.
the structure of the product obtained in this example was deduced from the above data:
example 24:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral scale tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of 3, 5-dimethylbenzeneboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the scale tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 91%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.60(d,J＝8.0Hz,2H),7.41-7.30(m,3H),6.80(s,3H),6.69(s,1H),6.40(d,J＝16.0Hz,1H),5.93(dt,J＝16.0,8.0Hz,1H),3.05(ddd,J＝80.0,12.0,8.0Hz,2H),2.18(s,6H).
13C NMR(101MHz,DMSO-d6)δppm 137.9,137.8,137.2,134.1,129.2,128.5,128.4,127.4,126.4(q,JC-F＝287.9Hz),124.1,123.0,76.4(q,JC-F＝27.3Hz),38.2,21.3.
19F NMR(376MHz,DMSO-d6)δppm-78.28.
the structure of the product obtained in this example was deduced from the above data:
example 25:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral graduated tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2-phenyl-4-penten-2-ol, 0.6 mmol of p-phenylphenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the graduated tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding salt solution and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a volume ratio of 100: 1: ethyl acetate mixture; the product yield was 91%.
The structural characterization data of the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.61(d,J＝8.0Hz,4H),7.56(d,J＝8.0Hz,2H),7.45-7.38(m,4H),7.35-7.28(m,4H),6.72(s,1H),6.53(d,J＝16.0Hz,1H),6.00(dt,J＝16.0,8.0Hz,1H),3.08(ddd,J＝88.0,16.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δppm 140.1,139.4,137.8,136.5,133.4,129.4,128.5,128.5,127.9,127.4,127.3,126.9,126.8,126.6(q,JC-F＝296.9Hz),123.8,76.4(q,JC-F＝26.3Hz),38.2.
19F NMR(376MHz,DMSO-d6)δppm-78.20.
the single crystal pattern of the product obtained in this example is shown in FIG. 4. This single crystal picture further demonstrates that the product structure is the E configuration.
The structure of the product obtained in this example was deduced from the above data:
example 26:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
to a spiral scale tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2- (4-methoxyphenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, and an oxygen balloon was fitted over the scale tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 95%.
The structural characterization data of the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.52(d,J＝8.0Hz,2H),7.27-7.15(m,5H),6.94(d,J＝8.0Hz,2H),6.61(s,1H),6.50(d,J＝16.0Hz,1H),5.98(dt,J＝16.0,8.0Hz,1H),3.74(s,3H),3.04(ddd,J＝84.0,16.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δppm 159.4,137.4,133.8,129.6,129.0,128.8,127.7,126.5(q,JC-F＝287.9Hz),126.2,123.7,113.8,76.1(q,JC-F＝27.3Hz),55.4,38.1.
19F NMR(376MHz,DMSO-d6)δppm-78.62.
the structure of the product obtained in this example was deduced from the above data:
example 27:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
to a spiral scale tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2- (4-methylphenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, and an oxygen balloon was fitted over the scale tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding salt solution and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is petroleum ether with a volume ratio of 100: 1: ethyl acetate mixture; the product yield was 91%.
The structural characterization data of the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.47(d,J＝8.0Hz,2H),7.27-7.15(m,7H),6.62(s,1H),6.48(d,J＝16.0Hz,1H),5.95(dt,J＝16.0.8.0.Hz,1H),3.03(ddd,J＝88.0,16.0,8.0Hz,2H),2.28(s,3H).
13C NMR(101MHz,DMSO-d6)δppm 137.7,137.3,134.8,133.8,129.0,127.7,127.3,126.4(q,JC-F＝287.9Hz),126.2,123.7,76.3(q,JC-F＝27.3Hz),38.1,21.1.
19F NMR(376MHz,DMSO-d6)δppm-78.43.
the structure of the product obtained in this example was deduced from the above data:
example 28:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
to a spiral scale tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2- (4-chlorophenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, and an oxygen balloon was applied to the scale tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 85%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.63(d,J＝8.0Hz,2H),7.45(d,J＝8.0Hz,2H),7.27-7.17(m,5H),6.87(s,1H),6.49(d,J＝16.0Hz,1H),5.95(dt,J＝16.0,8.0Hz,1H),3.07(ddd,J＝80.0,12.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δ137.2,136.8,134.2,133.5,129.4,129.0,128.5,127.8,126.3,126.2(q,JC-F＝288.9Hz),123.1,76.3(q,JC-F＝27.3Hz),38.0.
19F NMR(376MHz,DMSO-d6)δ-78.44.
the structure of the product obtained in this example was deduced from the above data:
example 29:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
to a spiral scale tube containing magnetons, 0.2 mmol of 1,1, 1-trifluoro-2- (4, 5-dichlorophenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the scale tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 94%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δppm 7.63(m,3H),7.32-7.17(m,5H),7.12(s,1H),6.53(d,J＝16.0Hz,1H),5.94(dt,J＝16.0,8.0Hz,1H),3.10(ddd,J＝120.0,16.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δppm 142.1,137.1,134.6,134.5,129.1,128.6,127.9,126.4,126.3,126.2(q,JC-F＝288.9Hz),122.7,76.2(q,JC-F＝26.3Hz),37.6.
19F NMR(376MHz,DMSO-d6)δppm-78.28.
the structure of the product obtained in this example was deduced from the above data:
example 30:
a method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives comprises the following steps:
in a spiral scale tube equipped with magnetons, 0.2 mmol of 1,1, 1-trifluoro-2- (3, 4-dimethoxyphenyl) -4-penten-2-ol, 0.6 mmol of phenylboronic acid, 0.01 mmol of tetrakis (triphenylphosphine) palladium, 1 ml of dimethyl sulfoxide and 1 ml of N, N-dimethylformamide were added, an oxygen balloon was fitted over the scale tube, and the reaction was stirred at 90 ℃ for 12 hours. Stopping heating and stirring, cooling to room temperature, simultaneously adding saline water and ethyl acetate to extract a reaction solution, performing reduced pressure rotary evaporation on ethyl acetate, removing a solvent, and performing column chromatography separation and purification to obtain a target product, wherein the volume ratio of column chromatography eluent is 100:1 petroleum ether: ethyl acetate mixture; the product yield was 88%.
The structural characterization data for the product obtained in this example are as follows:
1H NMR(400MHz,DMSO-d6)δ7.30-7.21(m,4H),7.21-7.10(m,3H),6.96(d,J＝8.5Hz,1H),6.63(s,1H),6.52(d,J＝16.0Hz,1H),5.99(dt,J＝16.0,7.0Hz,1H),3.75(s,3H),3.75(s,3H),3.05(ddd,J＝100.0,16.0,8.0Hz,2H).
13C NMR(101MHz,DMSO-d6)δppm 149.0,148.5,137.4,133.8,130.0,129.0,127.7,126.5(q,JC-F＝287.9Hz),126.3,123.8,120.0,111.5,111.5,76.2(q,JC-F＝26.3Hz),56.0,55.8,38.2.
19F NMR(376MHz,DMSO-d6)δppm-78.43.
the structure of the product obtained in this example was deduced from the above data:
the above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (9)
1. A (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative characterized by: the structure is shown as formula I:
wherein Ar1Is phenyl, p-methylphenyl, o-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, 3, 4-dimethoxyphenyl, p-fluorophenyl, o-fluorophenyl, p-chlorophenyl, o-chlorophenyl, 3, 5-dichlorophenyl, p-bromophenyl, o-bromophenyl or p-trifluoromethylphenyl;
Ar2is phenyl, p-tolyl, o-tolyl, p-methoxyphenyl, o-methoxyphenyl, p-methylthiophenyl, p-tert-butylphenyl, p-fluorophenyl, m-fluorophenyl, p-chlorophenyl, p-bromophenyl, o-bromophenyl, 3, 5-dimethylphenyl, p-methylsulfonylphenyl, p-phenylphenyl or 2-naphthyl;
R1is hydrogen, methyl or ethyl;
R2is hydrogen or fluorine;
R3is hydrogen, methyl or ethyl;
R4is hydrogen or methyl.
2. The method for synthesizing the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative according to claim 1, wherein: the method comprises the following steps:
taking an organic solvent as a reaction medium, and reacting the 1-fluoro-2-aryl-4-pentene-2-ol derivative with aryl boric acid under the action of a catalyst and oxygen to obtain a (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-ol derivative;
the 1-fluoro-2-aryl-4-penten-2-ol derivative is
Wherein Ar1Is phenyl, p-methylphenyl, o-methylphenyl, p-methoxyphenyl, o-methoxyphenyl, 3, 4-dimethoxyphenyl, p-fluorophenyl, o-fluorophenyl, p-chlorophenyl, o-chlorophenyl, 3, 5-dichlorophenyl, p-bromophenyl, o-bromophenyl or p-trifluoromethylphenyl;
R1is hydrogen, methyl or ethyl;
R2is hydrogen or fluorine;
R3is hydrogen, methyl or ethyl;
R4is hydrogen or methyl;
the arylboronic acid is Ar2B(OH)2Wherein Ar is2Is phenyl, p-tolyl, o-tolyl, p-methoxyphenyl, o-methoxyphenyl, p-methylthiophenyl, p-tert-butylphenyl, p-fluorophenyl, m-fluorophenyl, p-chlorophenyl, p-bromophenyl, o-bromophenyl, 3, 5-dimethylphenyl, p-methylsulfonylphenyl, p-phenylphenyl or 2-naphthyl;
the catalyst is more than one of palladium acetate, palladium iodide, palladium tetrakis (triphenylphosphine) and palladium dichlorodiphenylphosphine.
3. The method for synthesizing the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative according to claim 2, wherein:
the molar ratio of the 1-fluoro-2-aryl-4-penten-2-ol derivative to the arylboronic acid is 1:1-1: 4;
the catalyst is tetrakis (triphenylphosphine) palladium;
the organic solvent is more than one of N, N-dimethylformamide, dimethyl sulfoxide, toluene, nitromethane and tetrahydrofuran.
4. The method for synthesizing the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative according to claim 3, wherein: the molar ratio of the 1-fluoro-2-aryl-4-penten-2-ol derivative to the arylboronic acid is 1: (2-4);
the molar ratio of the catalyst to the 1-fluoro-2-aryl-4-penten-2-ol derivative is 1: (5-100);
the organic solvent is a mixed solvent of N, N-dimethylformamide and dimethyl sulfoxide.
5. The method for synthesizing the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative according to claim 2, wherein: the reaction is carried out in an oxygen atmosphere, the reaction temperature is 40-110 ℃, and the reaction time is 3-16 h.
6. The method for synthesizing (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivatives according to claim 5, wherein: the reaction temperature is 70-100 ℃, and the reaction time is 10-16 h.
7. The method for synthesizing the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative according to claim 2, wherein: and (2) performing subsequent treatment after the reaction is finished, cooling to room temperature after the reaction is finished, adding a salt solution or water and an organic solvent, extracting the reaction solution, performing reduced pressure rotary evaporation on an organic layer to remove the solvent to obtain a crude product, and performing column chromatography purification to obtain the (4E) -1-fluoro-2, 5-diaryl-4-pentene-2-ol derivative.
8. The method for synthesizing the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative according to claim 7, wherein: in the subsequent treatment, the organic solvent is ethyl acetate or dichloromethane;
the column chromatography purification refers to the purification by using petroleum ether: purifying by column chromatography with mixed solvent of ethyl acetate as eluent; petroleum ether: volume ratio of ethyl acetate: (20-500): 1.
9. Use of the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative according to claim 1, wherein: the (4E) -1-fluoro-2, 5-diaryl-4-penten-2-ol derivative is used in the fields of pesticides, medicines and materials.
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