CN117820065A - Gamma-aryl substituted gem-difluoro olefin compound and preparation method thereof - Google Patents

Gamma-aryl substituted gem-difluoro olefin compound and preparation method thereof Download PDF

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CN117820065A
CN117820065A CN202311561385.4A CN202311561385A CN117820065A CN 117820065 A CN117820065 A CN 117820065A CN 202311561385 A CN202311561385 A CN 202311561385A CN 117820065 A CN117820065 A CN 117820065A
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程立杰
李伟
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Hunan University
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Abstract

The invention discloses a preparation method of gamma-aryl substituted gem-difluoro olefin compounds, which comprises the following steps of dissolving a copper catalyst, a ligand and alkali in an organic solvent under the atmosphere of inert gas, stirring for reaction, then adding aryl borate, continuing stirring for reaction, then sequentially adding gem-difluoro-diene and alcohol for reaction, and purifying by column chromatography to obtain the gamma-aryl substituted gem-difluoro olefin compounds. The invention provides an efficient method for synthesizing gamma-aryl substituted gem-difluoro olefin compounds.

Description

Gamma-aryl substituted gem-difluoro olefin compound and preparation method thereof
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a gamma-aryl substituted gem-difluoro olefin compound and a preparation method thereof.
Background
Organofluorine compounds have wide and important applications in the fields of medicine, pesticides, materials and the like. The gem-difluoro olefin can be used as carbonyl bioelectrode isostere, so that the bioactivity, metabolic stability and lipophilicity of organic molecules are improved, and meanwhile, the gem-difluoro olefin can be also a key intermediate for synthesizing other organic fluorine compounds. How to synthesize geminal difluoroolefins efficiently has become a hotspot for organic synthesis research. Although many methods for preparing gem-difluoroolefins have recently been developed, methods for preparing gamma-aryl substituted gem-difluoroolefin compounds remain relatively limited. The currently available synthetic methods mainly involve rhodium-catalyzed defluorination arylation of trifluoromethyl olefin compounds with arylborates [ (a) Huang, y.; hayashi, t.j.am.chem.soc.2016,138,12340; (b) Jang, y.j.; rose, d.; mirabi b; lautens, M.Angew.Chem., int.Ed.,2018,57,16147], or rhodium catalyzes the hydroarylation of gem-difluorobinaenes with aromatic hydrocarbon carbon-hydrogen bonds containing directing groups (Wang, c.q.; li, z.q.; tian, l.; walsh, p.j.; feng, c.cell Reports Physical Science 2022,3,101117). However, the existing methods all need noble rhodium as a catalyst, and special arylboronic acid anhydride reagent, specific trifluoromethyl allylamide and aromatic hydrocarbon as reaction raw materials respectively, so that the application range of the substrate is limited, and the industrialized application of the methods is influenced. Therefore, the development of a synthesis method of gamma-aryl substituted gem-difluoroolefin compounds which is catalyzed by cheap metals and has wide substrate application is of great significance.
Disclosure of Invention
In order to solve the technical problems, the invention provides a gamma-aryl substituted gem-difluoro olefin compound and a preparation method thereof.
A gamma-aryl substituted gem-difluoroolefin compound having the following molecular formula:
wherein R is an alkyl group having various substituents and a cycloalkyl group, and the substituents on the R alkyl group include aryl, heteroaryl, alkoxy, alkylthio, silicon, boron, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, hydroxyl, alkynyl or halogen atoms;
ar is naphthyl, anthryl, furyl, thienyl, pyridyl or phenyl containing hydrocarbon groups, aryl groups, alkoxy groups, alkylthio groups, silicon groups, boron groups, ester groups, amide groups, cyano groups, trifluoromethyl groups, aldehyde groups, nitro groups, alkenyl groups and alkynyl groups.
A process for the preparation of said compound comprising the following reaction steps: under the inert gas atmosphere, dissolving a copper catalyst, a ligand and alkali into an organic solvent for stirring reaction, then adding aryl borate, continuing stirring reaction, then sequentially adding gem-difluoro-diene and alcohol for reaction, and purifying by column chromatography to obtain the gamma-aryl substituted gem-difluoro-alkene compound.
The invention is realized by the following technical scheme: stirring copper catalyst, ligand and alkali in an organic solvent for 0.5h in an inert gas atmosphere, adding aryl borate, continuously stirring for reacting for 0.5h, sequentially adding gem-difluoro-diene and alcohol, reacting for 12-24 h at 25-60 ℃, and purifying by column chromatography to obtain the gamma-aryl substituted gem-difluoro-alkene compound.
The specific reaction equation is:
wherein the molar ratio of said gem-difluorodiene to arylboronic acid ester is 1:1.5 to 2.0. And R in geminal difluoroallene is alkyl and cycloalkyl containing various substituents, wherein the substituents on the alkyl of R comprise aryl, heteroaryl, alkoxy, alkylthio, silicon, boron, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, hydroxy, alkynyl or halogen;
ar in the arylborate is naphthyl, anthryl, furyl, thienyl, pyridyl or phenyl containing alkyl, aryl, alkoxy, alkylthio, silicon base, boron base, ester base, amide base, cyano, trifluoromethyl, aldehyde base, nitro, alkenyl and alkynyl. Boron functionality (-B (OR') 2 ) Comprising boric acid (-B (OH) 2 ) Bis-pinacolato borate (-Bpin) and neopentyl glycol borate (-Bneop).
Copper catalysts include CuCN, cuCl, cuBr, cuI, cu (MeCN) 4 PF 6 、Cu(MeCN) 4 BF 4 、CuTc、(CF 3 SO 3 Cu) 2 C 6 H 6 . The copper catalyst is used in an amount of 0.05 to 0.2eq based on the molar amount of the geminal difluorodiene.
The ligands used include triphenylphosphine, tri-tert-butylphosphine, tricyclohexylphosphine, 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 2-dicyclohexylphosphine-2 ',4',6 '-triisopropylbiphenyl, 1, 3-bis (diphenylphosphine) propane, 1, 2-bis (diphenylphosphine) ethane, 1' -bis (diphenylphosphine) ferrocene, 2 '-bis (diphenylphosphine) -1,1' -binaphthyl, 1, 2-bis (diphenylphosphino) benzene. The dosage of the ligand is 1.2-2.4 eq of the molar quantity of the copper catalyst.
The base used includes LiOH, meOLi, t-Buoli and NaHCO 3 、Na 2 CO 3 、Na 3 PO 4 、NaH 2 PO 4 、Na 2 HPO 4 、NaHC 2 O 4 、Na 2 C 2 O 4 、CH 3 COONa、HCOONa、NaOH、MeONa、t-BuONa、KHCO 3 、K 2 CO 3 、K 3 PO 4 、KH 2 PO 4 、K 2 HPO 4 、CH 3 COOK, HCOOK, KOH, KOLi, t BuOK, triethylamine, diisopropylamine, trimethylamine, piperidine, pyridine. The amount of the base is 1.5 to 3.0eq based on the molar amount of the gem difluorodiene.
The alcohol used includes methanol, ethanol, isopropanol, tert-butanol, n-hexanol, and ethylene glycol. The alcohol is used in an amount of 1.5 to 3.0eq based on the molar amount of the gem-difluoro-diene.
Solvents used include 1, 4-dioxane, toluene, tetrahydrofuran, methylene chloride, toluene, acetonitrile, methyl tert-butyl ether.
The reaction temperature is 25-60 ℃ and the reaction time is 12-24 h.
The invention provides a method for synthesizing gamma-aryl substituted gem-difluoro olefin compounds. The method is simple and convenient to operate, can reduce the production cost, has a wider substrate application range, and provides a novel and efficient way for preparing gamma-aryl substituted gem-difluoro olefin compounds. In the invention, a conveniently and easily obtained gem-difluoro-biane compound and aryl borate are used as raw materials, metal copper complex and aryl borate are used for carrying out transfer metallization, then selective gamma-site addition is carried out on the gem-difluoro-biane, and protonation is carried out under the action of alcohol, so that the gamma-aryl substituted gem-difluoro-olefin compound is obtained. Compared with the defects and shortcomings of the prior art, the invention has the following beneficial effects: 1) The invention uses cheap copper as a catalyst, has low reaction cost and higher economic value than the prior report; 2) The reaction raw materials of the gem difluoro-biane compound and the aryl borate are simple and easy to obtain, the reaction conditions are mild, the application range of the substrate is wide, the product yield is high, and the method is favorable for industrial production.
Detailed Description
The examples are presented for better illustration of the invention, but the invention is not limited to the examples. Those skilled in the art will appreciate that various modifications and adaptations of the embodiments described above are possible in light of the above teachings and are intended to be within the scope of the invention.
The above and further technical features and advantages of the present invention will be described in more detail below with reference to the examples.
Example 1: preparation of (5, 5-difluoro-4-ene-1, 3-diyl) dibenzone (3 a)
To a 25mL reaction flask was added cuprous chloride (5.0 mg,0.05 mmol), 1, 2-bis (diphenylphosphine) ethane (23.9 mg,0.06 mmol), potassium t-butoxide (67.2 mg,0.6 mmol) and 1, 4-dioxane (10 mL) in this order under nitrogen atmosphere, stirred at room temperature for 30 minutes, then phenyl borate 2a (114 mg,0.6 mmol) was dissolved in 1, 4-dioxane (6 mL) and the above solution was added, followed by stirring for 30 minutes. Then, gem-difluorodiene compound 1a (72.1 mg,0.4 mmol) and isopropyl alcohol (48.1 mg,0.8 mmol) were added by a microinjection syringe, and the reaction was moved to 45℃and stirred for 16h. After the reaction, the solvent was concentrated under reduced pressure, then water (30 mL) and ethyl acetate (30 mL) were added to dilute the system, the organic phase was separated by extraction, the aqueous phase was extracted with ethyl acetate (2X 30 mL), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by column chromatography (petroleum ether as eluent) to give the desired product (5, 5-difluoro-4-ene-1, 3-yl) dibenzene (3 a) (94.3 mg, 91%).
1 H NMR(400MHz,Chloroform-d)δ7.42–7.15(m,10H),4.46(ddd,J＝24.8,10.2,2.7Hz,1H),3.52(q,J＝8.5Hz,1H),2.78–2.50(m,2H),2.26–1.90(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.14(t,J＝287.5Hz),143.83,141.66,128.71,128.41,128.38,127.07,126.65,125.93,82.52(t,J＝20.2Hz),39.26(d,J＝4.4Hz),38.41(t,J＝1.9Hz),33.65. 19 F NMR(376MHz,Chloroform-d)δ-88.71(d,J＝45.5Hz),-89.65(dd,J＝45.5,24.7Hz).
Example 2: preparation of (1-cyclohexyl-3, 3-difluoroall) benzene (3 b)
In the present example, 1b was used instead of 1a in example 1, and the other conditions were the same as in example 1, to obtain 55mg of (1-cyclohexyl-3, 3-difluoroall) benzene (3 b) as a target product in 58% yield.
1 H NMR(400MHz,Chloroform-d)δ7.37–7.29(m,2H),7.27–7.21(m,1H),7.20–7.14(m,2H),4.45(ddd,J＝24.6,10.8,2.8Hz,1H),3.26–3.08(m,1H),1.93–1.84(m,1H),1.83–1.74(m,1H),1.72–1.60(m,2H),1.60–1.50(m,1H),1.50–1.41(m,1H),1.32–1.08(m,3H),1.05–0.80(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.30(t,J＝286.4Hz),143.33(dd,J＝2.9,1.8Hz),128.59,127.79,126.49,81.38(t,J＝20.3Hz),46.36(d,J＝4.0Hz),43.22(t,J＝1.8Hz),31.43,30.72,26.52,26.37,26.33. 19 F NMR(377MHz,Chloroform-d)δ-88.83(d,J＝46.6Hz),-90.71(d,J＝46.7Hz).
Example 3: preparation of (8-chloro-1, 1-difluoro-1-en-3-yl) benzene (3 c)
In the present example, 1c was used in place of 1a in example 1, and the same conditions as in example 1 were applied to obtain 79mg of the target product (8-chloro-1, 1-difluoro-1-en-3-yl) benzene (3 c) in 76% yield.
1 H NMR(400MHz,Chloroform-d)δ7.37–7.29(m,2H),7.26–7.17(m,3H),4.38(ddd,J＝24.8,10.3,2.7Hz,1H),3.52(t,J＝6.7Hz,2H),3.49–3.39(m,1H),1.84–1.72(m,3H),1.72–1.61(m,1H),1.51–1.41(m,2H),1.41–1.22(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.14(t,J＝287.2Hz),144.15(t,J＝2.2Hz),128.77,127.10,126.68,82.68(t,J＝20.1Hz),45.12,39.69(d,J＝4.4Hz),36.76(t,J＝1.9Hz),32.58,26.81,26.75. 19 F NMR(377MHz,Chloroform-d)δ-89.01(d,J＝45.4Hz),-90.22(d,J＝45.3Hz).
Example 4: preparation of (1, 1-difluoro-trica-1, 12-dien-3-yl) benzene (3 d)
In the present example, 1d was used instead of 1a in example 1, and the other conditions were the same as in example 1 to obtain 83mg of (1, 1-difluorotrica-1, 12-dien-3-yl) benzene (3 d) as a target product in 71% yield.
1 H NMR(400MHz,Chloroform-d)δ7.40–7.15(m,5H),5.93–5.71(m,1H),5.11–4.87(m,2H),4.38(ddd,J＝24.8,10.3,2.7Hz,1H),3.44(q,J＝8.5Hz,1H),2.05(q,J＝7.0Hz,2H),1.81–1.61(m,2H),1.47–1.15(m,12H). 13 C NMR(101MHz,Chloroform-d)δ156.00(t,J＝285.8Hz),144.36,139.24,128.58,127.01,126.44,114.12,82.69(t,J＝20.1Hz),39.63(d,J＝4.3Hz),36.84,33.80,29.43,29.41,29.36,29.09,28.91,27.38. 19 F NMR(376MHz,Chloroform-d)δ-89.29(d,J＝46.4Hz),-90.49(dd,J＝46.5,24.8Hz).
Example 5: preparation of 1, 1-difluoroodec-1-en-3-yl) benzene (3 e)
In the example of the present invention, 1e was used in place of 1a in example 1, and the other conditions were the same as in example 1 to obtain 88mg of the objective product 1, 1-difluoroodec-1-en-3-yl) benzene (3 e) in 78% yield.
1 H NMR(400MHz,Chloroform-d)δ7.37–7.28(m,2H),7.25–7.17(m,3H),4.37(ddd,J＝25.0,10.4,2.7Hz,1H),3.44(q,J＝8.6Hz,1H),1.82–1.58(m,2H),1.33–1.22(m,14H),0.90(t,J＝6.7Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ156.17(t,J＝286.9Hz),144.52(t,J＝2.3Hz),128.72,127.15,126.57,82.85(t,J＝20.1Hz),39.79(d,J＝4.4Hz),37.01(t,J＝1.8Hz),32.04,29.71,29.67,29.55,29.45,27.55,22.83,14.25. 19 F NMR(376MHz,Chloroform-d)δ-89.29(d,J＝46.6Hz),-90.50(dd,J＝46.7,25.0Hz).
Example 6: preparation of 5- (5, 5-difluoro-2-methyl-3-phenyl-4-en-1-yl) benzol [ d ] [1,3] dioxin (3 f)
In the present example, 1f was used in place of 1a in example 1, and the other conditions were the same as in example 1 to obtain 98mg of 5- (5, 5-difluoro-2-methyl-3-phenyl-4-en-1-yl) benzol [ d ] [1,3] dioxyle (3 f) as a target product in 77% yield.
1 H NMR(400MHz,Chloroform-d)δ7.48–7.17(m,5H),6.84–6.73(m,1H),6.70–6.51(m,2H),5.96(s,2H),4.69–4.44(m,1H),3.49–3.30(m,1H),3.00–2.56(m,1H),2.29–1.95(m,2H),0.97–0.70(m,3H). 13 C NMR(101MHz,Chloroform-d)δ159.96–152.58(m),147.63,145.79,143.32(t,J＝2.3Hz),143.04–142.66(m),134.78(d,J＝3.6Hz),128.73,128.68,127.81,127.69,126.69,126.65,122.04,121.98,109.50,109.38,108.15(d,J＝1.8Hz),100.88(d,J＝1.3Hz),81.18(t,J＝20.4Hz),79.85(t,J＝20.6Hz),46.01(d,J＝4.2Hz),44.85(d,J＝4.3Hz),41.22(d,J＝1.9Hz),41.17,41.03(d,J＝1.9Hz),40.12,17.27,15.95. 19 F NMR(376MHz,Chloroform-d)δ-87.63–-88.08(m),-89.23–-89.63(m).
Example 7: preparation of 3- (6, 6-difluoro-4-phenylhex-5-en-1-yl) -1-methyl-1H-indole (3 g)
In the present example, 1g was used instead of 1a in example 1, and the other conditions were the same as in example 1 to obtain 93mg of the target product 3- (6, 6-difluoro-4-phenyl-5-en-1-yl) -1-methyl-1H-indole (3 g) in 71% yield.
1 H NMR(400MHz,Chloroform-d)δ7.57(d,J＝8.0Hz,1H),7.37–7.18(m,7H),7.11(t,J＝7.5Hz,1H),6.81(s,1H),4.39(ddt,J＝24.8,10.4,2.1Hz,1H),3.75(s,3H),3.51(q,J＝8.3Hz,1H),2.78(t,J＝7.2Hz,2H),1.94–1.62(m,4H). 13 C NMR(101MHz,Chloroform-d)δ156.14(t,J＝287.0Hz),144.33(t,J＝2.4Hz),137.17,128.74,128.00,127.19,126.61,126.19,121.56,119.12,118.65,115.02,109.24,82.81(t,J＝20.1Hz),39.68(d,J＝4.3Hz),36.76(d,J＝2.0Hz),32.68,28.29,24.94. 19 F NMR(376MHz,Chloroform-d)δ-89.14(d,J＝46.3Hz),-90.30(dd,J＝46.4,24.7Hz).
Example 8: preparation of 9- (8, 8-difluoro-6-phenyloct-7-en-1-yl) -9H-carbazole (3H)
In the present example, 1H was used instead of 1a in example 1, and the other conditions were the same as in example 1 to obtain 130mg of the target product 9- (8, 8-difluoro-6-phenyloct-7-en-1-yl) -9H-carbazole (3H), with a yield of 83%.
1 H NMR(400MHz,Chloroform-d)δ8.17(d,J＝7.7Hz,2H),7.52(t,J＝7.7Hz,2H),7.43(d,J＝8.2Hz,2H),7.39–7.23(m,5H),7.19(d,J＝7.5Hz,2H),4.46–4.25(m,3H),3.43(q,J＝8.5Hz,1H),1.91(p,J＝7.2Hz,2H),1.78–1.59(m,2H),1.49–1.25(m,4H). 13 C NMR(101MHz,Chloroform-d)δ156.09(t,J＝287.2Hz),144.11(t,J＝2.2Hz),140.52,128.74,127.07,126.65,125.71,122.95,120.48,118.87,108.74,82.65(t,J＝20.1Hz),43.02,39.75(d,J＝4.3Hz),36.81(t,J＝2.1Hz),28.96,27.33,27.21. 19 F NMR(376MHz,Chloroform-d)δ-88.98(d,J＝46.1Hz),-90.15(dd,J＝46.1,24.6Hz).
Example 9: preparation of (4, 4-difluoro-3-ene-1, 2-diyl) dibenzone (3 i)
In the present example, 1i was used instead of 1a in example 1, and the other conditions were the same as in example 1 to obtain 79mg of the target product (4, 4-difluoro-3-ene-1, 2-diyl) dibenzone (3 i), in 81% yield.
1 H NMR(400MHz,Chloroform-d)δ7.43–7.21(m,8H),7.15(d,J＝7.4Hz,2H),4.51(ddd,J＝24.5,10.2,2.7Hz,1H),3.84(q,J＝8.5Hz,1H),3.13(dd,J＝13.6,6.5Hz,1H),2.98(dd,J＝13.5,8.6Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ155.96(t,J＝287.8Hz),143.41(t,J＝2.1Hz),139.16,129.17,128.65,128.28,127.22,126.74,126.33,81.81(dd,J＝21.4,19.6Hz),43.48(t,J＝2.0Hz),41.62(d,J＝4.5Hz). 19 F NMR(376MHz,Chloroform-d)δ-88.52(d,J＝44.4Hz),-89.34(dd,J＝44.3,24.4Hz).
Example 10: preparation of 2- (5, 5-difluoro-3-phenyl-pent-4-en-1-yl) -5-methyl-furan (3 j)
In the example of the present invention, 1j was used instead of 1a in example 1, and the other conditions were the same as in example 1, to obtain 86mg of the target product 2- (5, 5-difluoro-3-phenyl-pent-4-en-1-yl) -5-methyl-furan (3 j) in 82% yield.
1 H NMR(400MHz,Chloroform-d)δ7.37(t,J＝7.4Hz,2H),7.32–7.22(m,3H),5.89(s,2H),4.45(ddd,J＝24.7,10.3,2.6Hz,1H),3.54(q,J＝8.6Hz,1H),2.74–2.51(m,2H),2.30(s,3H),2.21–1.94(m,2H). 13 C NMR(101MHz,Chloroform-d)δ154.78(t,J＝288.9Hz),150.46,143.63(t,J＝2.2Hz),128.73,127.10,126.70,105.85,105.72,82.29(t,J＝20.3Hz),39.08(d,J＝4.5Hz),35.11(t,J＝2.0Hz),26.04,13.52. 19 F NMR(376MHz,Chloroform-d)δ-88.56(d,J＝45.3Hz),-89.63(dd,J＝44.7,24.5Hz).
Example 11: preparation of (8- (benzoyloxy) -1, 1-difluoro-1-en-3-yl) benzene (3 k)
In the present example, 1k was used instead of 1a in example 1, and the other conditions were the same as in example 1 to obtain 118mg of the target product (8- (benzoyloxy) -1, 1-difluoro-1-en-3-yl) benzene (3 k) in 89% yield.
1 H NMR(400MHz,Chloroform-d)δ7.40–7.23(m,7H),7.23–7.13(m,3H),4.48(s,2H),4.34(ddd,J＝24.8,10.3,2.7Hz,1H),3.50–3.34(m,3H),1.77–1.67(m,1H),1.66–1.55(m,3H),1.43–1.29(m,3H),1.28–1.18(m,1H). 13 C NMR(101MHz,Chloroform-d)δ156.10(t,J＝287.0Hz),144.33(t,J＝2.2Hz),138.74,128.72,128.48,127.75,127.62,127.11,126.59,82.76(t,J＝20.1Hz),72.97,70.39,39.70(d,J＝4.4Hz),36.89(t,J＝1.9Hz),29.72,27.34,26.11. 19 F NMR(376MHz,Chloroform-d)δ-89.12(d,J＝46.5Hz),-90.32(dd,J＝46.4,24.9Hz).
Example 12: preparation of tert-butyl (8, 8-difluoro-6-phenyloct-7-en-1-yl) oxy) dimethyl-il-ane (3 l)
In the present example, 1l was used instead of 1a in example 1, and the other conditions were the same as in example 1, to obtain 118mg of the target product tert-butyl (8, 8-difluoro-6-phenyl-7-en-1-yl) dimethyl-ile (3 l), yield 83%.
1 H NMR(400MHz,Chloroform-d)δ7.40–7.32(m,2H),7.30–7.20(m,3H),4.41(ddd,J＝24.8,10.4,2.7Hz,1H),3.64(t,J＝6.5Hz,2H),3.54–3.39(m,1H),1.85–1.63(m,2H),1.61–1.48(m,2H),1.46–1.21(m,4H),0.95(s,9H),0.09(s,6H). 13 C NMR(101MHz,Chloroform-d)δ156.04(t,J＝287.8Hz),144.29(t,J＝2.2Hz),128.62,127.02,126.49,82.68(t,J＝20.1Hz),63.15,39.64(d,J＝4.4Hz),36.89(t,J＝1.9Hz),32.73,27.25,26.00,25.66,18.39,-5.27. 19 F NMR(377MHz,Chloroform-d)δ-89.18(d,J＝46.6Hz),-90.39(d,J＝46.7Hz).
Example 13: preparation of (5, 5-difluoro-3-phenyl-4-en-1-yl) (methyl) sulfane (3 m)
In the present example, 1m was used instead of 1a in example 1, and the other conditions were the same as in example 1, to obtain 81mg of (5, 5-difluoro-3-phenyl-pent-4-en-1-yl) (methyl) sulfane (3 m) as a target product in 83% yield.
1 H NMR(400MHz,Chloroform-d)δ7.39–7.31(m,2H),7.28–7.19(m,3H),4.42(ddd,J＝24.6,10.2,2.6Hz,1H),3.66(q,J＝8.2Hz,1H),2.56–2.37(m,2H),2.11(s,3H),2.08–1.92(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.17(t,J＝288.9Hz),143.19,128.77,127.06,126.78,82.07(t,J＝21.2Hz),38.63(d,J＝4.5Hz),36.00(t,J＝2.0Hz),31.86,15.43. 19 F NMR(376MHz,Chloroform-d)δ-88.34(d,J＝44.5Hz),-89.30(dd,J＝44.8,25.0Hz).
Example 14: preparation of 8,8-difluoro-6-phenyloct-7-en-1-ol (3 n)
In the present example, 1n was used instead of 1a in example 1, and the same conditions were used in example 1 to obtain 70mg of the target product 8,8-difluoro-6-phenyloct-7-en-1-ol (3 n) in 73% yield.
1 H NMR(400MHz,Chloroform-d)δ7.39–7.30(m,2H),7.28–7.13(m,3H),4.39(ddd,J＝24.8,10.3,2.7Hz,1H),3.63(t,J＝6.6Hz,2H),3.46(q,J＝8.5Hz,1H),1.80–1.67(m,2H),1.57(p,J＝6.7Hz,2H),1.44–1.26(m,4H). 13 C NMR(101MHz,Chloroform-d)δ156.04(t,J＝287.1Hz),144.17(t,J＝2.3Hz),128.62,127.00,126.51,82.64(t,J＝20.1Hz),62.81,39.60(d,J＝
4.4Hz),36.78(t,J＝1.9Hz),32.58,27.18,25.52. 19 F NMR(376MHz,Chloroform-d)δ-89.17(d,J＝46.7Hz),-90.35(dd,J＝46.6,24.9Hz).
Example 15: preparation of 2- (6, 6-difluoro-4-phenylhex-5-en-1-yl) -5,5-dimethyl-1,3-dioxane (3 o)
In the present example, 1a in example 1 was replaced with 1o, and the other conditions were the same as in example 1, to obtain 95mg of the target product 2- (6, 6-difluoro-4-phenyl-5-en-1-yl) -5,5-dimethyl-1,3-dioxane (3 o), with a yield of 76%.
1 H NMR(400MHz,Chloroform-d)δ7.36–7.27(m,2H),7.26–7.15(m,3H),4.44–4.30(m,2H),3.60(d,J＝11.1Hz,2H),3.41(d,J＝10.9Hz,2H),1.80–1.61(m,4H),1.53–1.31(m,2H),1.19(s,3H),0.72(s,3H). 13 C NMR(101MHz,Chloroform-d)δ156.04(dd,J＝287.7,286.4Hz),144.15(d,J＝1.8Hz),144.13(d,J＝1.6Hz),128.64,127.01,126.52,101.99,82.54(t,J＝21.2Hz),77.23,39.71(d,J＝4.3Hz),36.83(t,J＝2.0Hz),34.66,30.16,22.98,22.04,21.85. 19 F NMR(377MHz,Chloroform-d)δ-88.91(d,J＝45.4Hz),-90.19(d,J＝46.4Hz).
Example 16: preparation of 4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) benzonitrile (3 p)
In the present example, 2b was used instead of 2a in example 1, and the other conditions were the same as in example 1 to obtain 76mg of the target product 4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) benzonitrile (3 p) in 67% yield.
1 H NMR(400MHz,Chloroform-d)δ7.71–7.57(m,2H),7.39–7.26(m,4H),7.26–7.20(m,1H),7.19–7.08(m,2H),4.42(ddd,J＝24.4,10.1,2.4Hz,1H),3.55(q,J＝8.4Hz,1H),2.80–2.46(m,2H),2.19–1.89(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.39(t,J＝288.9Hz),149.26(t,J＝2.4Hz),140.94,132.58,128.55,128.34,127.96,126.20,118.77,110.67,81.43(dd,J＝21.9,19.6Hz),39.26(d,J＝4.6Hz),38.05(t,J＝1.8Hz),33.46. 19 F NMR(376MHz,Chloroform-d)δ-87.07(d,J＝41.8Hz),-87.96(dd,J＝42.0,24.5Hz).
Example 17: preparation of 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -4- (trifluoromethyl) benzene (3 q)
In the present example, 2a in example 1 was replaced with 2c, and the other conditions were the same as in example 1, to obtain 70mg of the objective product 1- (1, 1-difluoro-5-phenyl-5-en-3-yl) -4- (trifluoromethyl) benzene (3 q) in 53% yield.
1 H NMR(400MHz,Chloroform-d)δ7.59(d,J＝7.9Hz,2H),7.36–7.26(m,4H),7.26–7.19(m,1H),7.16(d,J＝7.5Hz,2H),4.42(ddd,J＝24.5,10.1,2.4Hz,1H),3.55(q,J＝8.5Hz,1H),2.76–2.49(m,2H),2.16–1.92(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.31(t,J＝288.4Hz),147.85,141.17,128.50,128.35,127.45,126.11,125.68(q,J＝3.8Hz),81.83(dd,J＝21.3,20.0Hz),39.06(d,J＝4.5Hz),38.19,33.51. 19 F NMR(376MHz,Chloroform-d)δ-62.45,-87.69(d,J＝43.0Hz),-88.56(dd,J＝43.1,24.4Hz).
Example 18: preparation of 1-chloro-4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) benzene (3 r)
In the present example, 2d was used instead of 2a in example 1, and the other conditions were the same as in example 1 to obtain 107mg of the objective product 1-chloro-4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) benzene (3 r) in 92% yield.
1 H NMR(400MHz,Chloroform-d)δ7.39–7.27(m,4H),7.26–7.11(m,5H),4.40(ddd,J＝24.6,10.1,2.6Hz,1H),3.48(q,J＝8.4Hz,1H),2.77–2.48(m,2H),2.18–1.85(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.31(t,J＝288.0Hz),142.40(t,J＝2.3Hz),141.48,132.48,128.95,128.59,128.56,128.48,126.16,82.29(dd,J＝21.0,19.7Hz),38.73(d,J＝4.4Hz),38.42(t,J＝2.0Hz),33.65. 19 F NMR(376MHz,Chloroform-d)δ-88.13(d,J＝44.2Hz),-88.99(dd,J＝44.1,24.6Hz).
Example 19: preparation of 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -4-fluorobenzene (3 s)
In the example of the present invention, 2e was used instead of 2a in example 1, and the other conditions were the same as in example 1 to obtain 104mg of the target product 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -4-fluorobenzene (3 s) in 94% yield.
1 H NMR(400MHz,Chloroform-d)δ7.37–7.27(m,2H),7.27–7.12(m,5H),7.10–6.98(m,2H),4.41(ddd,J＝24.7,10.2,2.6Hz,1H),3.49(q,J＝8.5Hz,1H),2.74–2.50(m,2H),2.14–1.92(m,2H). 13 C NMR(101MHz,Chloroform-d)δ162.79,160.36,156.13(t J＝288.9Hz),141.44,139.49,128.51,128.44,128.35,126.00,115.46(d,J＝21.3Hz),82.42(t,J＝20.3Hz),38.48(d,J＝4.4Hz),33.56. 19 F NMR(376MHz,Chloroform-d)δ-88.47(d,J＝45.1Hz),-89.33(dd,J＝45.1,24.9Hz).
Example 20: preparation of 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) naphthalene (3 t)
In the example of the present invention, 2f was used in place of 2a in example 1, and the other conditions were the same as in example 1 to obtain 116mg of the target product 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) naphthalene (3 t) in 94% yield.
1 H NMR(400MHz,Chloroform-d)δ8.08–7.88(m,2H),7.81(d,J＝7.9Hz,1H),7.62–7.43(m,4H),7.37(t,J＝7.4Hz,2H),7.32–7.21(m,3H),4.62(ddd,J＝23.9,10.2,3.7Hz,1H),4.43–4.30(m,1H),2.95–2.58(m,2H),2.43–2.04(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.18(t,J＝287.8Hz),141.58,139.94(t,J＝2.2Hz),134.12,131.23,129.07,128.55,128.48,127.30,126.18,126.06,125.63,125.55,123.41,122.91,82.47(t J＝19.2Hz),38.34(t,J＝2.0Hz),34.12(d,J＝4.3Hz),33.91. 19 F NMR(376MHz,Chloroform-d)δ-88.46(d,J＝44.3Hz),-88.74(dd,J＝45.2,23.7Hz).
Example 21: preparation of 4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -1,1' -biphen yl (3 u)
In the present example, 2g was used instead of 2a in example 1, and the other conditions were the same as in example 1 to obtain 130mg of the target product 4- (1, 1-difluoro-5-phenyl-5-en-3-yl) -1,1' -biphen yl (3 u) in 71% yield.
1 H NMR(400MHz,Chloroform-d)δ7.82–7.67(m,4H),7.65–7.55(m,2H),7.55–7.40(m,5H),7.40–7.29(m,3H),4.60(ddd,J＝24.8,10.3,2.6Hz,1H),3.80–3.57(m,1H),2.98–2.61(m,2H),2.38–2.05(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.32(t,J＝287.6Hz),143.01(t,J＝2.2Hz),141.76,140.96,139.77,128.95,128.60,128.57,127.64,127.59,127.39,127.20,126.13,82.62(t,J＝20.1Hz),39.03(d,J＝4.4Hz),38.53(t,J＝2.0Hz),33.81. 19 F NMR(376MHz,Chloroform-d)δ-88.29(d,J＝44.7Hz),-89.31(dd,J＝45.3,24.9Hz).
Example 22: preparation of 1-bromoo-4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) benzene (3 v)
In the present example, 2h was used instead of 2a in example 1, and the other conditions were the same as in example 1 to obtain 122mg of the objective product 1-bromo4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) benzene (3 v) in a yield of 90%.
1 H NMR(400MHz,Chloroform-d)δ7.50(d,J＝8.2Hz,2H),7.35(t,J＝7.4Hz,2H),7.26(t,J＝7.3Hz,1H),7.20(d,J＝7.5Hz,2H),7.13(d,J＝8.1Hz,2H),4.43(ddd,J＝24.6,10.1,2.6Hz,1H),3.49(q,J＝8.4Hz,1H),2.78–2.51(m,2H),2.18–1.92(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.22(t,J＝288.1Hz),142.83(t,J＝2.3Hz),141.36,131.81,128.86,128.50,128.39,126.08,120.42,82.12(dd,J＝21.0,19.7Hz),38.70(d,J＝4.4Hz),38.26(t,J＝2.0Hz),33.55. 19 F NMR(376MHz,Chloroform-d)δ-88.05(d,J＝44.0Hz),-88.90(dd,J＝43.9,24.4Hz).
Example 23: preparation of 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -4-methoxybenzene (3 w)
In the present example, 2a in example 1 was replaced with 2i, and the other conditions were the same as in example 1 to obtain 101mg of the target product 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -4-methoxybenzene (3 w), yield 87%.
1 H NMR(400MHz,Chloroform-d)δ7.38–7.30(m,2H),7.28–7.13(m,5H),6.99–6.81(m,2H),4.43(ddd,J＝24.8,10.3,2.7Hz,1H),3.85(s,3H),3.58–3.38(m,1H),2.78–2.47(m,2H),2.17–1.89(m,2H). 13 C NMR(101MHz,Chloroform-d)δ158.30,156.05(t,J＝287.8Hz),141.76,135.93(t,J＝2.3Hz),128.43,128.02,125.93,114.09,82.81(t,J＝19.9Hz),55.30,38.54(t,J＝1.9Hz),38.41(d,J＝4.4Hz),33.67. 19 F NMR(376MHz,Chloroform-d)δ-89.02(d,J＝46.0Hz),-89.92(dd,J＝46.3,24.9Hz).
Example 24: preparation of 4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) benzaldehyde (3X)
In the example of the present invention, 2j was used instead of 2a in example 1, and the other conditions were the same as in example 1 to obtain 60mg of the target product 4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) benzaldehyde (3 x), with a yield of 52%.
1 H NMR(400MHz,Chloroform-d)δ10.02(s,1H),7.87(d,J＝7.8Hz,2H),7.39(d,J＝7.9Hz,2H),7.31(q,J＝6.4,5.4Hz,2H),7.23(t,J＝7.3Hz,1H),7.17(d,J＝7.5Hz,2H),4.46(ddd,J＝24.5,10.2,2.4Hz,1H),3.58(q,J＝8.4Hz,1H),2.83–2.47(m,2H),2.25–1.92(m,2H). 13 C NMR(101MHz,Chloroform-d)δ191.75,156.33(t,J＝288.9Hz),150.87(t,J＝2.4Hz),141.11,135.17,130.25,128.51,128.34,127.80,126.12,81.65(dd,J＝21.6,19.7Hz),39.38(d,J＝4.5Hz),38.17(t,J＝2.0Hz),33.52. 19 F NMR(376MHz,Chloroform-d)δ-87.44(d,J＝42.6Hz),-88.35(dd,J＝42.8,25.0Hz).
Example 25: preparation of methyl4- (1, 1-difluoro-5-phenyl-5-en-3-yl) benzoate (3 y)
In the present example, 2k was used instead of 2a in example 1, and the other conditions were the same as in example 1, to obtain 119mg of methyl4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) benzoate (3 y) as a target product in 94% yield.
1 H NMR(400MHz,Chloroform-d)δ8.04(d,J＝8.2Hz,2H),7.40–7.27(m,4H),7.27–7.12(m,3H),4.46(ddd,J＝24.6,10.1,2.5Hz,1H),3.95(s,3H),3.57(q,J＝8.5Hz,1H),2.77–2.50(m,2H),2.19–1.95(m,2H). 13 C NMR(101MHz,Chloroform-d)δ166.97,156.36(t,J＝288.2Hz),149.14(t,J＝2.3Hz),141.37,130.18,128.79,128.57,128.46,127.24,126.16,81.98(dd,J＝21.4,19.7Hz),52.14,39.32(d,J＝4.5Hz),38.31(t,J＝1.8Hz),33.63. 19 F NMR(376MHz,Chloroform-d)δ-87.81(d,J＝43.5Hz),-88.73(dd,J＝43.6,24.8Hz).
Example 26: preparation of 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -4-methyl-zene (3 z)
In the present example, 2l was used instead of 2a in example 1, and the other conditions were the same as in example 1 to obtain 99mg of the target product 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -4-methylparaben (3 z) in 91% yield.
1 H NMR(400MHz,Chloroform-d)δ7.36–7.29(m,2H),7.26–7.09(m,7H),4.44(ddd,J＝24.8,10.2,2.7Hz,1H),3.49(q,J＝8.5Hz,1H),2.75–2.52(m,2H),2.38(s,3H),2.19–1.93(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.09(t,J＝287.8Hz),141.74,140.81(t,J＝2.3Hz),136.20,129.38,128.38,126.93,125.89,82.69(t,J＝20.1Hz),38.84(d,J＝4.4Hz),38.40(t,J＝2.1Hz),33.66,20.98. 19 F NMR(376MHz,Chloroform-d)δ-88.96(d,J＝45.8Hz),-89.89(dd,J＝46.4,24.9Hz).
Example 27: preparation of 4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) dibenzo [ b, d ] furane (3 aa)
In the present example, 2m was used instead of 2a in example 1, and the other conditions were the same as in example 1, to obtain 123mg of the objective product 4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) dibenzo [ b, d ] furane (3 aa), with a yield of 88%.
1 H NMR(400MHz,Chloroform-d)δ8.04(d,J＝7.7Hz,1H),7.98–7.88(m,1H),7.70(d,J＝8.2Hz,1H),7.61–7.51(m,1H),7.49–7.34(m,5H),7.33–7.21(m,3H),4.90(ddd,J＝24.7,10.4,2.6Hz,1H),4.14(q,J＝8.6Hz,1H),2.92–2.65(m,2H),2.51–2.21(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.46(dd,J＝288.3,286.9Hz),156.10,153.95,141.70,128.50,128.45,127.76(t,J＝2.2Hz),127.25,125.99,125.64,124.63,124.40,123.09,122.83,120.76,119.12,111.87,81.36(dd,J＝21.5,19.4Hz),37.17(t,J＝2.1Hz),35.49(d,J＝4.8Hz),33.90. 19 F NMR(376MHz,Chloroform-d)δ-88.34(d,J＝44.4Hz),-88.97(dd,J＝44.6,24.7Hz).
Example 28: preparation of 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -4-vinyllbenzene (3 ab)
In the example of the present invention, 2n was used instead of 2a in example 1, and the other conditions were the same as in example 1 to obtain 109mg of the target product 1- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -4-vinyllbenzene (3 ab) in 96% yield.
1 H NMR(400MHz,Chloroform-d)δ7.48(d,J＝7.9Hz,2H),7.39(t,J＝7.4Hz,2H),7.34–7.20(m,5H),6.81(dd,J＝17.6,10.9Hz,1H),5.84(d,J＝17.5Hz,1H),5.34(d,J＝10.8Hz,1H),4.51(ddd,J＝24.8,10.2,2.6Hz,1H),3.58(q,J＝8.4Hz,1H),2.84–2.56(m,2H),2.24–2.00(m,2H). 13 C NMR(101MHz,Chloroform-d)δ156.21(t,J＝288.9Hz),143.50(t,J＝2.3Hz),141.68,136.54,136.20,128.51,128.47,127.33,126.65,126.04,113.64,82.50(t,J＝20.2Hz),39.03(d,J＝4.4Hz),38.40(t,J＝1.9Hz),33.69. 19 F NMR(376MHz,Chloroform-d)δ-88.48(d,J＝44.9Hz),-89.43(dd,J＝44.9,24.7Hz).
Example 29: preparation of 4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -N, N-dimethyllbenzemide (3 ac)
In the present example, 2a in example 1 was replaced with 2o, and the other conditions were the same as in example 1 to obtain 115mg of the target product 4- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) -N, N-dimethyl zamide (3 ac) in 87% yield.
1 H NMR(400MHz,Chloroform-d)δ7.41(d,J＝7.8Hz,2H),7.35–7.13(m,7H),4.43(ddd,J＝24.7,10.2,2.5Hz,1H),3.51(q,J＝8.4Hz,1H),3.07(d,J＝47.7Hz,6H),2.75–2.48(m,2H),2.16–1.94(m,2H). 13 C NMR(101MHz,Chloroform-d)δ171.47,156.15(t,J＝288.9Hz),145.34(t,J＝2.3Hz),141.41,134.68,128.46,128.38,127.60,127.07,126.01,82.17(dd,J＝20.9,19.8Hz),39.65,39.05(d,J＝4.5Hz),38.29(t,J＝1.9Hz),35.39,33.54. 19 F NMR(376MHz,Chloroform-d)δ-88.19(d,J＝44.2Hz),-89.08(dd,J＝44.6,25.4Hz).
Example 30: preparation of 3- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) pyridine (3 ad)
In the examples of the present invention, 2p was used instead of 2a in example 1, and the other conditions were the same as in example 1 to obtain 77mg of the target product 3- (1, 1-difluoro-5-phenyl-pent-1-en-3-yl) pyridine (3 ad) in 74% yield.
1 H NMR(400MHz,Chloroform-d)δ8.53(s,2H),7.53(d,J＝7.9Hz,1H),7.36–7.26(m,3H),7.26–7.13(m,3H),4.44(ddd,J＝24.5,10.1,2.4Hz,1H),3.52(q,J＝8.5Hz,1H),2.84–2.46(m,2H),2.21–1.87(m,3H). 13 C NMR(101MHz,Chloroform-d)δ156.29(t,J＝289.9Hz),148.89,148.13,141.04,134.44,128.53,128.35,126.14,81.64(dd,J＝21.6,19.7Hz),38.11(t,J＝1.7Hz),36.80(d,J＝4.6Hz),33.48. 19 F NMR(376MHz,Chloroform-d)δ-87.46(d,J＝42.2Hz),-88.21(dd,J＝42.8,24.3Hz).
In the above description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, the foregoing description is only a preferred embodiment of the invention, which can be practiced otherwise than as specifically described herein, and therefore the invention is not limited to the specific details disclosed herein. And any person skilled in the art can make many possible variations and modifications to the technical solution of the present invention or modify equivalent experimental examples of equivalent variations by using the methods and technical contents disclosed above without departing from the scope of the technical solution of the present invention. Any simple modification, equivalent variation and modification of the above experimental examples according to the technical substance of the present invention without departing from the technical proposal of the present invention still falls within the scope of the technical proposal of the present invention.

Claims (10)

1. A gamma-aryl substituted gem-difluoroolefin compound, characterized in that said gamma-aryl substituted gem-difluoroolefin compound has the following molecular formula:
wherein R is an alkyl group having various substituents and a cycloalkyl group, and the substituents on the R alkyl group include aryl, heteroaryl, alkoxy, alkylthio, silicon, boron, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, hydroxyl, alkynyl or halogen atoms;
ar is naphthyl, anthryl, furyl, thienyl, pyridyl or phenyl containing hydrocarbon groups, aryl groups, alkoxy groups, alkylthio groups, silicon groups, boron groups, ester groups, amide groups, cyano groups, trifluoromethyl groups, aldehyde groups, nitro groups, alkenyl groups and alkynyl groups.
2. The compound of claim 1, wherein the compound has the following molecular formula:
wherein R is an alkyl group having various substituents and a cycloalkyl group, and the substituents on the R alkyl group include aryl, heteroaryl, alkoxy, alkylthio, silicon, boron, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, hydroxyl, alkynyl or halogen atoms.
3. The compound of claim 1, wherein the compound has the following molecular formula:
wherein Ar is naphthyl, anthryl, furyl, thienyl, pyridyl or phenyl containing hydrocarbon groups, aryl groups, alkoxy groups, alkylthio groups, silicon groups, boron groups, ester groups, amide groups, cyano groups, trifluoromethyl groups, aldehyde groups, nitro groups, alkenyl groups and alkynyl groups.
4. A process for the preparation of a compound according to any one of claims 1 to 3, comprising the reaction steps of: under the inert gas atmosphere, dissolving a copper catalyst, a ligand and alkali into an organic solvent for stirring reaction, then adding aryl borate, continuing stirring reaction, then sequentially adding gem-difluoro-diene and alcohol for reaction, and purifying by column chromatography to obtain the gamma-aryl substituted gem-difluoro-alkene compound.
5. The method according to claim 4, wherein Ar in the arylboronic acid ester is naphthyl, anthryl, furyl, thienyl, pyridyl or phenyl containing hydrocarbon group, aryl group, alkoxy group, alkylthio group, silicon group, boron group, ester group, amide group, cyano group, trifluoromethyl group, aldehyde group, nitro group, alkenyl group and alkynyl group; boron functionality (-B (OR') 2 ) Comprising boric acid (-B (OH) 2 ) Bis-pinacolato borate (-Bpin) and neopentyl glycol borate (-Bneop).
6. The process of claim 4 wherein R in said gem-difluorodiene is an alkyl group having various substituents and a cycloalkyl group, wherein the substituents on the alkyl group of R include aryl, heteroaryl, alkoxy, alkylthio, silicon, boron, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, hydroxy, alkynyl or halogen.
7. The method of claim 4, wherein the copper catalyst comprises CuCN, cuCl, cuBr, cuI, cu (MeCN) 4 PF 6 、Cu(MeCN) 4 BF 4 、CuTc、(CF 3 SO 3 Cu) 2 C 6 H 6 。
8. The method according to claim 4, wherein the ligand comprises triphenylphosphine, tri-t-butylphosphine, tricyclohexylphosphine, 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 2-dicyclohexylphosphine-2 ',4',6 '-triisopropylbiphenyl, 1, 3-bis (diphenylphosphine) propane, 1, 2-bis (diphenylphosphine) ethane, 1' -bis (diphenylphosphine) ferrocene, 2 '-bis (diphenylphosphine) -1,1' -binaphthyl, 1, 2-bis (diphenylphosphino) benzene.
9. The preparation method according to claim 4, wherein the base comprises LiOH, meOLi, t-Buoli, naHCO 3 、Na 2 CO 3 、Na 3 PO 4 、NaH 2 PO 4 、Na 2 HPO 4 、NaHC 2 O 4 、Na 2 C 2 O 4 、CH 3 COONa、HCOONa、NaOH、MeONa、t-BuONa、KHCO 3 、K 2 CO 3 、K 3 PO 4 、KH 2 PO 4 、K 2 HPO 4 、CH 3 COOK, HCOOK, KOH, KOLi, t BuOK, triethylamine, diisopropylamine, trimethylamine, piperidine, pyridine.
10. The method according to claim 4, wherein the alcohol comprises methanol, ethanol, isopropanol, tert-butanol, n-hexanol, or ethylene glycol.
CN202311561385.4A 2023-11-22 2023-11-22 Gamma-aryl substituted gem-difluoro olefin compound and preparation method thereof Pending CN117820065A (en)

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