CN118026807A - Process for preparing 1, 1-difluoro substituted-1, 3-eneyne compounds - Google Patents
Process for preparing 1, 1-difluoro substituted-1, 3-eneyne compounds Download PDFInfo
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 38
- 238000004519 manufacturing process Methods 0.000 title description 2
- 239000011941 photocatalyst Substances 0.000 claims abstract description 18
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 125000003118 aryl group Chemical group 0.000 claims abstract description 7
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims abstract description 6
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 3
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052707 ruthenium Inorganic materials 0.000 claims abstract description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 150000002367 halogens Chemical group 0.000 claims description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 5
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 5
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 38
- 239000000758 substrate Substances 0.000 abstract description 6
- 230000003321 amplification Effects 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 252
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 42
- 238000004293 19F NMR spectroscopy Methods 0.000 description 42
- 238000005160 1H NMR spectroscopy Methods 0.000 description 42
- 230000000694 effects Effects 0.000 description 13
- 239000002904 solvent Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 150000002332 glycine derivatives Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- -1 p-toluenesulfonyl hydrazone Chemical class 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of a1, 1-difluoro substituted-1, 3-eneyne compound, which comprises the following steps: reacting a compound of formula (1) with a compound of formula (2) in the presence of a photocatalyst and a base under the condition of blue light irradiation to produce a1, 1-difluoro-1, 3-eneyne compound of formula (3); wherein R 1 is selected from substituted or unsubstituted C1-C10 chain alkyl, substituted or unsubstituted C3-C10 cyclic alkyl, substituted or unsubstituted aryl, heteroaryl; the compound of formula (2) is a carboxylic acid; the photocatalyst is selected from metallic iridium photocatalyst, metallic ruthenium photocatalyst and carbazole photocatalyst. The preparation method has the advantages of cheap and easily available reaction raw materials, simple and convenient reaction operation, wide application range of reaction substrates, easy amplification of reaction, mild reaction conditions and the like, and can realize industrial production and application.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of a1, 1-difluoro substituted-1, 3-eneyne compound.
Background
The research of organic fluorine chemistry is an important field, and because fluorine atoms have the characteristics of large electronegativity and small atomic radius, the physicochemical properties of fluorine-containing compounds can be effectively improved, so that the fluorine-containing compounds have partially unique properties. Therefore, the fluorine-containing compound plays an important role in a series of fields closely related to human life, such as biological medicine, agrochemical, and material chemistry.
1, 1-Difluoro-substituted-1, 3-eneynes are a very important class of organic synthesis intermediates, and can be converted into various fluorine-containing compounds through various chemical transformations.
Chinese patent publication CN104844410a discloses a method for synthesizing 1, 1-difluoro-1, 3-eneyne compound, in which p-toluenesulfonyl hydrazone of α, α, α -trifluoromethyl ketone is reacted with a terminal alkyne compound in an organic solvent, and under the catalysis of monovalent copper CuX, in the presence of a base and an additive, the 1, 1-difluoro-1, 3-eneyne compound is obtained. The process requires the use of a metal catalyst.
By starting from 2-trifluoromethyl-substituted-1, 3-eneyne, the 1, 1-difluoro-substituted-1, 3-eneyne can be successfully obtained by means of a free radical polarity cross-coupling strategy. In 2023, the Guo group reported a synthesis of 1, 1-difluoro-substituted-1, 3-eneynes based on amine oxidative deprotonation strategy (Yuan, z.—h.; xin, h.; zhang, l.; gao, p.; yang, x.; man, x.; h.; guo, l.; n.; green chem.; 2023,25,6733-6738) which disclosed a metal-free, visible light driven difluoroalkenylation of glycine derivatives with trifluoromethyl olefins substituted for 1, 3-ynes as shown in the following equation:
however, this technique has obvious drawbacks: the reaction is only applicable to glycine derivatives as radical precursors.
The existing method for synthesizing 1, 1-difluoro substituted-1, 3-eneyne has the defects of severe reaction conditions and narrower reaction substrates.
Disclosure of Invention
The invention provides a preparation method of a1, 1-difluoro substituted-1, 3-eneyne compound, which firstly realizes the synthesis of various 1, 1-difluoro substituted-1, 3-eneyne compounds under the condition of photoinduction by taking simple and easily obtained carboxylic acid as a free radical precursor.
The technical scheme of the invention is as follows:
A process for the preparation of a1, 1-difluoro-substituted-1, 3-eneyne compound comprising: reacting a compound of formula (1) with a compound of formula (2) in the presence of a photocatalyst and a base under blue light irradiation to produce a1, 1-difluoro-1, 3-eneyne compound of formula (3):
Wherein R 1 is selected from substituted or unsubstituted C1-C10 chain alkyl, substituted or unsubstituted C3-C10 cyclic alkyl, substituted or unsubstituted aryl, heteroaryl;
The compound of formula (2) is a carboxylic acid;
the photocatalyst is selected from metallic iridium photocatalyst, metallic ruthenium photocatalyst and carbazole photocatalyst.
The compounds of formula (2) may be primary carboxylic acids, secondary carboxylic acids, tertiary carboxylic acids, natural amino acids, and drug-derived carboxylic acids.
Preferably, R 2 is selected from the group consisting of substituted or unsubstituted C1-C10 chain alkyl, substituted or unsubstituted C3-C10 cyclic alkyl, substituted or unsubstituted C3-C10 heterocycloalkyl, substituted or unsubstituted C1-C10 alkoxy, substituted or unsubstituted aryl, heteroaryl.
Preferably, in R 1, the substituents on the substituted chain alkyl are halogen and/or ester groups; the substituent on the substituted cyclic alkyl group is a cyclic alkyl group; the substituent on the substituted aryl and heteroaryl is halogen, substituted or unsubstituted C1-C6 alkoxy and substituted or unsubstituted C1-C6 alkyl;
In R 2, the substituent on the substituted alkyl is halogen and/or ester; the substituent on the substituted alkoxy is halogen and/or ester; the substituent on the substituted aryl and heteroaryl is halogen substituted or unsubstituted C1-C6 alkyl, halogen substituted or unsubstituted C1-C6 alkoxy, halogen and/or ester, and the substituent on the substituted aryl and heteroaryl is halogen, substituted or unsubstituted C1-C6 alkoxy and substituted or unsubstituted C1-C6 alkyl.
Aryl is phenyl or naphthyl; heteroaryl is benzothienyl.
Preferably, the compound of formula (1) is selected from:
The compound of formula (2) is selected from:
preferably, the catalyst is selected from:
Preferably, the wavelength of the blue light is 390-440 nm; more preferably 427nm or 440nm.
Preferably, the reaction is carried out in an organic solvent, wherein the organic solvent is at least one of acetonitrile, dimethyl sulfoxide, ethylene glycol dimethyl ether and tetrahydrofuran.
Preferably, the base is an organic base or an inorganic base; the organic base is at least one of triethylamine and diisopropylethylamine; the inorganic base is at least one of potassium carbonate, potassium phosphate, potassium hydroxide, sodium hydroxide and dipotassium hydrogen phosphate.
Preferably, the molar ratio of the compound of formula (1), the compound of formula (2), the base, and the photocatalyst is 1:0.5-1.5:0.5-1.5:0.01-0.05.
The reaction temperature is room temperature; the reaction temperature is preferably 25 to 30 ℃.
The 1, 1-difluoro substituted-1, 3-eneyne compound prepared by the invention is an important organic synthesis intermediate, and can be converted into various fluorine-containing compounds through various chemical reactions.
Compared with the prior art, the invention has the beneficial effects that:
(1) The invention realizes the synthesis of various 1, 1-difluoro substituted-1, 3-eneyne compounds under the condition of photoinduction by taking simple and easily obtained carboxylic acid as a free radical precursor for the first time.
(2) The preparation method provided by the invention can be applied to primary carboxylic acid, secondary carboxylic acid, tertiary carboxylic acid, natural amino acid and medicine derived carboxylic acid, and has the advantages of simple and easily obtained substrate and wide universality.
(3) The preparation method has the advantages of cheap and easily available reaction raw materials, simple and convenient reaction operation, wide application range of reaction substrates, easy amplification of reaction, mild reaction conditions and the like, and can realize industrial production and application.
Detailed Description
The present invention will be described in further detail with reference to the following examples, which are intended to facilitate the understanding of the present invention without any limitation thereto.
The methods of operation, under which specific conditions are not noted in the examples below, are generally in accordance with conventional conditions, or in accordance with the conditions recommended by the manufacturer. The amount of photocatalyst in each example was based on compound 1, unless otherwise specified.
In the following examples, the photocatalyst is:
Example 1: effect of PC2 on the reaction
In a glove box, PC2 (3 mol%), carboxylic acid 2, potassium carbonate were weighed into a 4mL sample bottle, and solvent MeCN (2.0 mL), 1, 3-eneyne 1 (0.1 mmol) were added sequentially, and the PTFE cap was screwed in. The vial was taken out of the glove box and placed under 440nm blue light and reacted at 25℃for 12 hours. After the reaction is finished, the solvent is removed by a rotary evaporator to obtain a crude product. The catalyst is removed by filtration through a short silica gel column, and the conversion rate and the yield of the reaction are analyzed by thin layer chromatography or nuclear magnetic resonance, and the experimental result is obtained: the nuclear magnetic yield was 89%.
Example 2: effect of PC1 on the reaction
The only difference from example 1 is that PC2 is replaced by an equimolar amount of PC1, the remainder being the same, the experimental results obtained: the nuclear magnetic yield was 25%.
Example 3: effect of PC3 on the reaction
The only difference from example 1 is that PC2 is replaced by an equimolar amount of PC3, the remainder being the same, the experimental results obtained: the nuclear magnetic yield was 56%.
Example 4: effect of PC4 on the reaction
The only difference from example 1 is that PC2 is replaced by an equimolar amount of PC4, the remainder being the same, the experimental results obtained: the nuclear magnetic yield was 75%.
Example 5: effects of 427nm blue light on reaction
The difference from example 1 is only that the blue light wavelength is 427nm, the rest is the same, and the experimental result is obtained: the nuclear magnetic yield was 85%.
Example 6: effect of THF solvent on the reaction
The only difference from example 1 is that the solvent MeCN is replaced by an equal volume of THF, the rest being the same, the experimental results obtained: the nuclear magnetic yield was 39%.
Example 7: effect of DMSO solvent on the reaction
The only difference from example 1 is that the solvent MeCN is replaced by an equal volume of DMSO, the rest being the same, the experimental results obtained: the nuclear magnetic yield was 80.
Example 8: effect of DME solvent on the reaction
The only difference from example 1 is that the solvent MeCN is replaced by an equal volume of DME, the rest being the same, the experimental results obtained: the nuclear magnetic yield was 65%.
Example 9: effect of NaOH on the reaction
The difference from example 1 is only that the same amount of NaOH is used instead of the base K 2CO3, the rest being the same, the experimental results obtained being: the nuclear magnetic yield was 65%.
Example 10: effect of KOH on reaction
The only difference from example 1 is that the base K 2CO3 is replaced by an equal amount of KOH, the rest being the same, the experimental results obtained: the nuclear magnetic yield was 35%.
Example 11: influence of triethylamine on the reaction
The difference from example 1 is only that the base K 2CO3 is replaced by an equal amount of triethylamine, the rest being the same, the experimental results obtained: the nuclear magnetic yield was 20%.
Example 12: effect of K 3PO4 on the reaction
The only difference from example 1 is that the base K 2CO3 is replaced by an equal amount of K 3PO4, the rest being the same, the experimental results obtained: the nuclear magnetic yield was 24%.
Example 13: effect of dipotassium Hydrogen phosphate on the reaction
The difference from example 1 is only that the base K 2CO3 is replaced by an equal amount of dipotassium hydrogen phosphate, the rest being the same, the experimental results obtained: the nuclear magnetic yield was 31%.
Example 14: effect of diisopropylethylamine on the reaction
The difference from example 1 is only that the base K 2CO3 is replaced by an equal amount of diisopropylethylamine, the rest being the same, the experimental results obtained: the nuclear magnetic yield was 15%.
Example 15: examination of 1, 3-eneyne and carboxylic acid substrates
In a glove box, PC2 (3 mol%), carboxylic acid 2, potassium carbonate were weighed into a 4mL sample bottle, and solvent MeCN (2.0 mL), 1, 3-eneyne 1 (0.1 mmol) were added sequentially, and the PTFE cap was screwed in. The vial was taken out of the glove box and placed under 440nm blue light and reacted at 25℃for 12 hours. After the reaction is finished, the solvent is removed by a rotary evaporator to obtain a crude product. The catalyst was removed by filtration through a short silica gel column, and the conversion rate and isolation yield of the reaction were analyzed by thin layer chromatography or nuclear magnetic resonance, and the experimental results obtained are shown in Table 1.
TABLE 1 examination of 1, 3-eneyne and carboxylic acid substrates
Analytical data for compounds 3-44 are as follows:
analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 3
1H NMR(400MHz,CDCl3)δ7.44–7.36(m,2H),7.35–7.27(m,3H),3.81–3.71(m,2H),3.66(ddd,J＝11.8,8.8,3.1Hz,2H),2.19(t,J＝2.2Hz,2H),1.66(ddd,J＝13.2,8.8,4.1Hz,2H),1.50–1.37(m,2H),1.11(s,3H).
13C NMR(101MHz,CDCl3)δ159.73(dd,J＝296.9,294.2Hz),131.13(s),128.33(two carbons,s),122.91(s),93.40(t,J＝5.8Hz),82.74(dd,J＝8.1,4.2Hz),75.32(dd,J＝34.3,15.2Hz),63.86(s),39.36(s),37.30(s),32.59(t,J＝2.4Hz),23.85(s).
19F NMR(377MHz,CDCl3)δ-78.22(d,J＝13.0Hz),-82.38(d,J＝12.7Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 4
1H NMR(400MHz,CDCl3)δ7.42–7.31(m,2H),7.05–6.96(m,2H),3.80–3.70(m,2H),3.65(ddd,J＝11.8,8.9,3.1Hz,2H),2.17(t,J＝2.1Hz,2H),1.65(ddd,J＝13.2,8.8,4.1Hz,2H),1.51–1.36(m,2H),1.10(s,3H).
13C NMR(101MHz,CDCl3)δ162.50(d,J＝249.7Hz),159.75(dd,J＝296.9,294.4Hz),133.02(d,J＝8.4Hz),119.00(d,J＝3.5Hz),115.64(d,J＝22.1Hz),92.29(t,J＝5.8Hz),82.42(dd,J＝8.1,4.2Hz),75.19(dd,J＝34.6,15.2Hz),63.82(s),39.37(s),37.27(s),32.59(t,J＝2.4Hz),23.78(s).
19F NMR(377MHz,CDCl3)δ-78.16(d,J＝12.6Hz),-82.18(d,J＝12.6Hz),-110.61–-110.74(m).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 5
1H NMR(400MHz,CDCl3)δ7.35–7.26(m,4H),3.80–3.71(m,2H),3.65(ddd,J＝11.9,8.9,3.1Hz,2H),2.17(t,J＝2.2Hz,2H),1.64(ddd,J＝13.3,8.9,4.1Hz,2H),1.49–1.36(m,2H),1.10(s,3H).
13C NMR(101MHz,CDCl3)δ159.83(dd,J＝297.5,294.7Hz),134.41(s),132.34(s),128.71(s),121.41(s),92.29(t,J＝5.8Hz),83.76(dd,J＝8.2,4.2Hz),75.22(dd,J＝34.5,15.2Hz),63.84(s),39.38(s),37.30(s),32.62(t,J＝2.5Hz),23.80(s).
19F NMR(377MHz,CDCl3)δ-77.75(d,J＝11.0Hz),-81.76(d,J＝11.8Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 6
1H NMR(400MHz,CDCl3)δ7.57(d,J＝8.3Hz,2H),7.49(d,J＝8.2Hz,2H),3.81–3.71(m,2H),3.65(ddd,J＝11.9,9.0,3.1Hz,2H),2.19(t,J＝2.1Hz,2H),1.65(ddd,J＝13.3,9.0,4.1Hz,2H),1.48–1.37(m,2H),1.11(s,3H).
13C NMR(151MHz,CDCl3)δ160.03(dd,J＝298.3,295.4Hz),131.34(s),130.05(q,J＝32.7Hz),126.67(s),125.29(q,J＝3.4Hz),123.84(q,J＝272.2Hz),92.04(t,J＝5.6Hz),85.27(dd,J＝8.2,4.2Hz),75.09(dd,J＝34.6,15.0Hz),63.82(s),39.39(s),37.25(s),32.64(s),23.70(s).
19F NMR(377MHz,CDCl3)δ-62.85(s),-76.89(d,J＝9.5Hz),-80.79(d,J＝9.5Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 7
1H NMR(400MHz,CDCl3)δ7.38–7.30(m,2H),6.88–6.80(m,2H),3.81(s,3H),3.76(ddd,J＝11.5,5.3,4.3Hz,2H),3.65(ddd,J＝11.8,8.7,3.2Hz,2H),2.17(t,J＝2.2Hz,2H),1.65(ddd,J＝13.2,8.8,4.1Hz,2H),1.48–1.39(m,2H),1.10(s,3H).
13C NMR(151MHz,CDCl3)δ159.66(s),159.56(dd,J＝296.4,294.0Hz),132.60(s),115.07(s),113.98(s),93.33(t,J＝5.6Hz),81.35(dd,J＝8.0,4.0Hz),75.43(dd,J＝34.1,15.3Hz),63.88(s),55.29(s),39.39(s),37.33(s),32.59(s),23.91(s).
19F NMR(377MHz,CDCl3)δ-79.06(d,J＝14.5Hz),-83.29(d,J＝14.9Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 8
1H NMR(400MHz,CDCl3)δ7.92(s,1H),7.85–7.74(m,3H),7.53–7.41(m,3H),3.84–3.73(m,2H),3.68(ddd,J＝11.8,8.8,3.1Hz,2H),2.22(t,J＝2.1Hz,2H),1.69(ddd,J＝13.2,8.8,4.1Hz,2H),1.52–1.43(m,2H),1.14(s,3H).
13C NMR(151MHz,CDCl3)δ159.85(dd,J＝297.2,294.5Hz),132.93(s),132.81(s),130.95(s),128.04(s),127.89(s),127.76(s),127.73(s),126.73(s),126.62(s),120.22(s),93.83(t,J＝5.9Hz),83.10(dd,J＝7.8,4.3Hz),75.44(dd,J＝34.3,15.1Hz),63.90(s),39.45(s),37.37(s),32.67(s),23.90(s).
19F NMR(377MHz,CDCl3)δ-78.06(d,J＝12.5Hz),-82.19(d,J＝12.4Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 9
1H NMR(400MHz,CDCl3)δ7.37(d,J＝1.4Hz,1H),7.07–6.99(m,2H),3.80–3.72(m,2H),3.65(ddd,J＝11.8,8.7,3.1Hz,2H),3.09–2.95(m,2H),2.18(t,J＝2.1Hz,2H),1.97–1.90(m,2H),1.66(ddd,J＝13.1,8.7,4.1Hz,2H),1.49–1.39(m,2H),1.32(s,6H),1.10(s,3H).
13C NMR(151MHz,CDCl3)δ159.60(t,J＝295.4Hz),142.04(s),133.19(s),129.06(s),128.52(s),126.51(s),118.21(s),93.83–93.64(m),81.92(dd,J＝7.7,3.8Hz),75.43(dd,J＝33.8,15.3Hz),63.88(s),39.37(s),37.32(s),37.17(s),32.90(s),32.61(s),29.91(s),23.89(s),23.16(s).
19F NMR(377MHz,CDCl3)δ-78.69(d,J＝14.8Hz),-82.96(d,J＝14.0Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 10
1H NMR(400MHz,CDCl3)δ3.74–3.65(m,5H),3.61(ddd,J＝11.8,8.9,3.1Hz,2H),2.67–2.57(m,2H),2.52(dd,J＝11.3,4.4Hz,2H),2.02(t,J＝2.2Hz,2H),1.56(ddd,J＝13.3,8.8,4.2Hz,2H),1.39–1.28(m,2H),1.02(s,3H).
13C NMR(101MHz,CDCl3)δ172.11(s),160.06(dd,J＝295.3,292.5Hz),92.07(t,J＝5.7Hz),74.88(dd,J＝34.0,15.6Hz),74.54(dd,J＝8.0,3.8Hz),63.80(s),51.74(s),39.41(s),37.26(s),33.16(s),32.48(t,J＝2.5Hz),23.72(s),15.33(s).
19F NMR(377MHz,CDCl3)δ-80.43(d,J＝17.5Hz),-83.85(d,J＝17.5Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 11
1H NMR(400MHz,CDCl3)δ3.72(dt,J＝9.6,4.5Hz,2H),3.66–3.56(m,4H),2.49(t,J＝6.8Hz,2H),2.04(t,J＝2.2Hz,2H),1.96(p,J＝6.6Hz,2H),1.58(ddd,J＝13.3,8.9,4.2Hz,2H),1.40–1.31(m,2H),1.04(s,3H).
13C NMR(101MHz,CDCl3)δ160.10(dd,J＝295.0,292.8Hz),92.17(t,J＝5.7Hz),74.93(dd,J＝30.2,19.2Hz),74.82(t,J＝4.0Hz),63.81(s),43.50(s),39.52(s),37.27(s),32.51(t,J＝2.5Hz),31.16(s),23.72(s),16.80(s).
19F NMR(377MHz,CDCl3)δ-80.47(d,J＝17.8Hz),-83.78(d,J＝17.7Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 12
1H NMR(400MHz,CDCl3)δ5.74(s,1H),3.75–3.67(m,2H),3.66–3.57(m,2H),2.45–2.17(m,5H),2.10–1.97(m,4H),1.78–1.65(m,3H),1.65–1.50(m,7H),1.47–1.26(m,7H),1.20(s,3H),1.05(s,3H),0.90(s,3H).
13C NMR(151MHz,CDCl3)δ199.46(s),170.98(s),159.94(t,J＝295.2Hz),123.89(s),96.56(t,J＝5.8Hz),80.01(s),79.47(dd,J＝8.1,3.8Hz),74.59(dd,J＝34.1,15.3Hz),63.75(s),53.58(s),50.08(s),46.97(s),39.42(s),38.76(s),38.56(s),37.24(s),37.17(s),36.15(s),35.69(s),33.88(s),32.69(s),32.50(s),31.52(s),23.75(s),23.02(s),20.67(s),17.37(s),12.76(s).
19F NMR(377MHz,CDCl3)δ-78.42(d,J＝13.8Hz),-82.12(d,J＝13.8Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 13
1H NMR(400MHz,CDCl3)δ7.00(d,J＝7.5Hz,1H),6.66(d,J＝7.5Hz,1H),6.62(s,1H),5.73(s,1H),3.92(t,J＝6.4Hz,2H),2.48–2.21(m,8H),2.17(s,3H),2.08–1.93(m,4H),1.90–1.64(m,6H),1.63–1.49(m,2H),1.48–1.22(m,6H),1.19(s,3H),1.09–0.79(m,12H).
13C NMR(101MHz,CDCl3)δ199.49(s),171.06(s),159.89(dd,J＝295.9,294.9Hz),156.94(s),136.43(s),130.29(s),123.89(s),123.57(s),120.78(s),112.21(s),96.26(t,J＝5.6Hz),80.04(s),79.66(dd,J＝8.2,4.0Hz),75.40(dd,J＝33.9,14.9Hz),68.63(s),53.53(s),50.03(s),46.98(s),39.16(d,J＝2.0Hz),38.75(s),38.57(s),38.15(s),36.18(s),35.69(s),34.58(t,J＝2.4Hz),33.91(s),32.73(s),32.51(s),31.50(s),26.87(s),26.82(s),24.31(s),23.03(s),21.36(s),20.69(s),17.38(s),15.75(s),12.76(s).
19F NMR(377MHz,CDCl3)δ-78.97(d,J＝14.5Hz),-82.67(d,J＝14.5Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 14
1H NMR(400MHz,CDCl3)δ7.74–7.66(m,2H),7.41–7.34(m,2H),7.08(d,J＝8.4Hz,2H),6.96–6.85(m,2H),6.45(t,J＝6.1Hz,1H),5.72(s,1H),3.64(dd,J＝15.0,7.1Hz,2H),2.85(t,J＝7.1Hz,2H),2.51–2.29(m,5H),2.23(dt,J＝9.2,7.4Hz,2H),2.07–1.95(m,2H),1.69–1.46(m,7H),1.38–1.22(m,9H),1.17(s,3H),0.96–0.70(m,6H).
13C NMR(151MHz,CDCl3)δ199.86(s),171.50(s),166.32(s),160.16(t,J＝295.3Hz),153.66(s),137.56(s),133.80(s),132.97(s),129.25(s),128.74(s),128.35(s),123.85(s),123.74(s),96.38(t,J＝5.5Hz),80.10(s),79.96(t,J＝2.6Hz),79.16(dd,J＝8.1,4.1Hz),74.87(dd,J＝33.4,16.8Hz),53.32(s),49.88(s),46.97(s),41.22(s),39.77(s),38.74(s),38.59(s),36.13(s),35.70(s),34.88(s),34.01(s),32.76(s),32.47(s),31.36(s),26.59(s),26.12(s),23.02(s),20.64(s),17.32(s),12.76(s).
19F NMR(377MHz,CDCl3)δ-78.35(d,J＝12.4Hz),-82.39(d,J＝12.4Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 15
1H NMR(400MHz,CDCl3)δ7.10(d,J＝8.1Hz,2H),6.93(d,J＝7.9Hz,2H),5.71(d,J＝2.4Hz,1H),2.83(t,J＝9.5Hz,1H),2.48–2.28(m,5H),2.27–2.15(m,2H),2.09–1.90(m,4H),1.77(dd,J＝16.7,9.2Hz,2H),1.70–1.34(m,8H),1.30(d,J＝10.2Hz,7H),1.16(s,3H),0.89–0.74(m,5H).
13C NMR(151MHz,CDCl3)δ199.56(s),171.25(s),160.14(t,J＝295.4Hz),154.32(s),129.70(s),129.35(s),123.76(s),123.74(s),96.58(s),80.22(d,J＝1.6Hz),80.02(s),78.96(dd,J＝7.7,4.2Hz),74.85(dd,J＝34.0,16.1Hz),60.81(s),53.31(s),53.25(s),49.84(d,J＝2.0Hz),46.97(s),40.02(s),38.73(s),38.52(s),36.09(d,J＝1.5Hz),35.63(s),34.85(s),33.89(s),32.70(s),32.42(s),31.32(s),31.26(s),26.34(d,J＝2.7Hz),26.08(s),26.03(s),25.82(s),23.00(s),20.64(s),17.32(s),12.73(s).
19F NMR(377MHz,CDCl3)δ-78.38(t,J＝11.8Hz),-82.40(t,J＝12.5Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 16
1H NMR(400MHz,CDCl3)δ7.41(dd,J＝6.6,3.0Hz,2H),7.35–7.26(m,3H),2.07(t,J＝2.2Hz,2H),1.02(s,9H).
13C NMR(151MHz,CDCl3)δ159.65(dd,J＝296.3,294.3Hz),131.17(s),128.28(s),128.20(s),123.18(s),93.13(t,J＝5.9Hz),83.08(dd,J＝8.4,4.2Hz),76.46(dd,J＝34.4,14.7Hz),41.06(d,J＝1.8Hz),32.40(s),29.31(s).
19F NMR(377MHz,CDCl3)δ-79.16(d,J＝13.8Hz),-83.24(d,J＝14.0Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 17
1H NMR(400MHz,CDCl3)δ7.45–7.37(m,2H),7.34–7.25(m,3H),2.24(t,J＝2.2Hz,2H),2.11–1.99(m,2H),1.98–1.81(m,2H),1.81–1.70(m,2H),1.21(s,3H).
13C NMR(101MHz,CDCl3)δ159.53(dd,J＝296.3,293.0Hz),131.19(s),128.32(s),128.25(s),123.17(s),93.34(t,J＝5.6Hz),82.29(dd,J＝8.0,3.9Hz),76.34(d,J＝14.4Hz),39.20(s),39.18(s),39.15(s),33.34(s),25.72(s),15.37(s).
19F NMR(377MHz,CDCl3)δ-79.72(d,J＝15.3Hz),-84.32(d,J＝16.0Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 18
1H NMR(400MHz,CDCl3)δ7.43–7.37(m,2H),7.33–7.26(m,3H),2.11(t,J＝2.2Hz,2H),1.55–1.39(m,8H),1.38–1.30(m,2H),0.99(s,3H).
13C NMR(101MHz,CDCl3)δ159.63(dd,J＝296.3,293.8Hz),131.16(s),128.28(s),128.16(s),123.22(s),92.95(t,J＝5.7Hz),83.23(dd,J＝8.2,4.1Hz),75.90(dd,J＝34.5,14.7Hz),39.09(s),37.56(s),34.75(s),26.31(s),25.01(s),22.06(s).
19F NMR(377MHz,CDCl3)δ-78.83(d,J＝13.9Hz),-82.81(d,J＝13.9Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 19
1H NMR(400MHz,CDCl3)δ7.43–7.35(m,2H),7.32(dd,J＝4.1,2.3Hz,3H),2.41(t,J＝6.3Hz,4H),2.28(t,J＝2.1Hz,2H),1.96–1.84(m,2H),1.78(dt,J＝13.3,6.5Hz,2H),1.19(s,3H).
13C NMR(101MHz,CDCl3)δ211.84(s),159.85(dd,J＝297.4,294.5Hz),131.19(s),128.53(s),128.42(s),122.75(s),93.56(t,J＝5.8Hz),82.33(dd,J＝8.1,4.1Hz),75.52(dd,J＝34.2,15.7Hz),53.46(s),37.83(d,J＝2.0Hz),37.61(s),37.05(s),34.27(t,J＝2.3Hz),23.99(s).
19F NMR(377MHz,CDCl3)δ-77.74(d,J＝12.1Hz),-82.19(d,J＝12.1Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 20
1H NMR(400MHz,CDCl3)δ7.45–7.39(m,2H),7.35–7.28(m,3H),1.98(s,3H),1.94(d,J＝1.9Hz,2H),1.72(s,1H),1.69(s,2H),1.65(s,2H),1.61(s,7H).
13C NMR(151MHz,CDCl3)δ159.55(dd,J＝296.3,294.1Hz),131.19(s),128.28(s),128.16(s),123.22(s),92.94(t,J＝5.8Hz),83.40(dd,J＝8.2,3.9Hz),75.10(dd,J＝34.9,14.8Hz),42.13(s),41.86(d,J＝2.4Hz),36.88(s),34.22(s),28.60(s).
19F NMR(377MHz,CDCl3)δ-78.92(d,J＝13.9Hz),-82.69(d,J＝13.9Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 21
1H NMR(400MHz,CDCl3)δ7.44–7.35(m,2H),7.34–7.27(m,3H),2.56(s,2H),2.16–2.15(m,1H),2.07–1.79(m,12H).
13C NMR(101MHz,CDCl3)δ217.85(s),159.63(dd,J＝297.6,294.4Hz),131.16(s),128.42(s),128.33(s),122.78(s),93.55(t,J＝5.8Hz),82.50(dd,J＝8.0,4.3Hz),74.78(dd,J＝34.6,15.5Hz),46.31(s),43.12(s),40.77(s),39.97(d,J＝2.1Hz),38.55(s),34.15(t,J＝2.4Hz),27.75(s).
19F NMR(377MHz,CDCl3)δ-78.01(d,J＝12.4Hz),-82.20(d,J＝12.4Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 22
1H NMR(400MHz,CDCl3)δ7.44–7.38(m,2H),7.35–7.27(m,3H),3.66(s,3H),2.36(t,J＝2.0Hz,2H),2.05(s,6H).
13C NMR(151MHz,CDCl3)δ170.34(s),159.12(dd,J＝296.9,293.8Hz),131.26(s),128.43(s),128.34(s),122.77(s),93.59(t,J＝5.8Hz),81.43–81.03(m),75.94(dd,J＝35.0,15.6Hz),51.94(s),51.60(s),38.45(t,J＝3.1Hz),37.98(s),29.69(s).
19F NMR(377MHz,CDCl3)δ-79.53(d,J＝15.2Hz),-85.29(d,J＝16.1Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 23
1H NMR(400MHz,CDCl3)δ7.48–7.40(m,2H),7.36–7.27(m,3H),4.74(s,1H),2.55(s,2H),1.39(s,15H).
13C NMR(151MHz,CDCl3)δ160.04(t,J＝296.2Hz),154.23(s),131.36(s),128.39(s),128.24(s),122.83(s),93.62(t,J＝5.7Hz),82.05(s),78.87(s),75.36(dd,J＝33.9,16.2Hz),52.99(t,J＝2.3Hz),37.09(s),28.34(s),27.15(s).
19F NMR(377MHz,CDCl3)δ-77.72(d,J＝7.5Hz),-82.42(d,J＝7.5Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 24
1H NMR(400MHz,CDCl3)δ7.47–7.37(m,2H),7.35–7.27(m,3H),4.83(s,1H),3.08(d,J＝6.7Hz,2H),2.10(t,J＝1.9Hz,2H),1.45(s,9H),0.99(s,6H).
13C NMR(101MHz,CDCl3)δ159.74(dd,J＝297.4,294.4Hz),156.23(s),131.24(s),128.49(s),128.37(s),122.72(s),93.50(t,J＝5.7Hz),82.58(dd,J＝8.0,4.1Hz),79.14(s),75.51(dd,J＝34.4,15.3Hz),49.74(s),37.00(s),36.44(s),28.40(s),24.90(s).
19F NMR(377MHz,CDCl3)δ-77.92(d,J＝12.2Hz),-82.41(d,J＝12.2Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 25
1H NMR(400MHz,CDCl3)δ7.45–7.38(m,2H),7.36–7.28(m,3H),5.88(ddt,J＝17.7,10.4,7.4Hz,1H),5.11–5.00(m,2H),2.10(s,1H),2.10–2.05(m,3H),0.99(s,6H).
13C NMR(101MHz,CDCl3)δ159.65(dd,J＝296.3,294.3Hz),135.09(s),131.16(s),128.29(s),128.24(s),123.08(s),117.43(s),93.21(t,J＝5.7Hz),82.94(dd,J＝7.9,4.0Hz),76.09(dd,J＝34.2,15.0Hz),46.47(s),39.06(d,J＝2.0Hz),35.03(t,J＝2.4Hz),26.62(s).
19F NMR(377MHz,CDCl3)δ-78.67(d,J＝13.9Hz),-82.75(d,J＝13.4Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 26
1H NMR(400MHz,CDCl3)δ7.48–7.40(m,2H),7.36–7.28(m,3H),3.98(dd,J＝10.8,3.6Hz,2H),3.40(td,J＝11.8,2.0Hz,2H),2.10(dt,J＝7.2,2.3Hz,2H),1.93–1.78(m,1H),1.69(dd,J＝13.1,1.7Hz,2H),1.35(ddd,J＝25.0,12.0,4.4Hz,2H).
13C NMR(101MHz,CDCl3)δ159.17(dd,J＝296.6,293.4Hz),131.38(s),128.42(s),128.34(s),122.85(s),93.39(t,J＝5.8Hz),81.14(dd,J＝8.2,4.2Hz),76.76(dd,J＝58.3,23.3Hz),67.85(s),34.27(d,J＝1.2Hz),33.81(t,J＝2.1Hz),32.47(s).
19F NMR(377MHz,CDCl3)δ-79.21(d,J＝16.3Hz),-84.53(d,J＝15.6Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 27
1H NMR(400MHz,CDCl3)δ7.47–7.39(m,2H),7.37–7.27(m,3H),4.11(s,2H),2.72(t,J＝12.0Hz,2H),2.14–2.02(m,2H),1.82–1.66(m,3H),1.46(s,9H),1.23–1.07(m,2H).
13C NMR(101MHz,CDCl3)δ159.11(dd,J＝296.7,293.2Hz),154.80(s),131.36(s),128.41(s),128.32(s),122.78(s),93.48–93.31(m),81.09(dd,J＝8.2,4.1Hz),79.30(s),76.68(d,J＝34.9Hz),43.68(s),34.82(t,J＝2.0Hz),33.90(d,J＝1.1Hz),31.52(s),28.42(s).
19F NMR(377MHz,CDCl3)δ-79.15(d,J＝15.3Hz),-84.44(d,J＝15.6Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 28
1H NMR(400MHz,CDCl3)δ7.48–7.39(m,2H),7.36–7.28(m,3H),2.03(dt,J＝7.1,2.2Hz,2H),1.84–1.57(m,6H),1.35–1.12(m,3H),0.95(qd,J＝12.0,2.4Hz,2H).
13C NMR(151MHz,CDCl3)δ159.04(dd,J＝295.9,292.7Hz),131.39(s),128.28(s),128.24(s),123.07(s),93.00(t,J＝5.7Hz),81.65(dd,J＝8.1,4.0Hz),77.46(d,J＝14.3Hz),36.33(s),34.74(s),32.68(s),26.40(s),26.10(s).
19F NMR(377MHz,CDCl3)δ-79.91(d,J＝17.8Hz),-85.06(d,J＝17.5Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 29
1H NMR(400MHz,CDCl3)δ7.46–7.40(m,2H),7.36–7.30(m,3H),2.75–2.55(m,4H),2.16–2.01(m,4H),1.71–1.60(m,1H),1.41(ddd,J＝25.0,11.7,3.5Hz,2H).
13C NMR(151MHz,CDCl3)δ159.16(dd,J＝296.6,293.2Hz),131.39(s),128.44(s),128.34(s),122.81(s),93.44(t,J＝5.6Hz),81.08(dd,J＝7.9,4.1Hz),76.53(d,J＝15.2Hz),35.88(s),34.65(s),33.49(s),28.58(s).
19F NMR(377MHz,CDCl3)δ-79.04(d,J＝15.2Hz),-84.37(d,J＝15.5Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 30
1H NMR(400MHz,CDCl3)δ7.48–7.39(m,2H),7.36–7.27(m,3H),5.68(s,2H),2.66–2.47(m,3H),2.22(dt,J＝7.4,2.2Hz,2H),2.12–2.02(m,2H).
13C NMR(151MHz,CDCl3)δ159.14(dd,J＝295.9,292.8Hz),131.38(s),129.64(s),128.30(s),122.98(s),93.31(t,J＝5.8Hz),81.35(dd,J＝8.2,4.0Hz),78.15(dd,J＝34.5,14.5Hz),38.35(s),35.93(t,J＝1.8Hz),33.32(d,J＝1.5Hz).
19F NMR(377MHz,CDCl3)δ-79.84(d,J＝16.7Hz),-84.98(d,J＝16.9Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 31
1H NMR(400MHz,CDCl3)δ7.47–7.39(m,2H),7.35–7.27(m,3H),4.14(p,J＝6.8Hz,1H),3.90(dd,J＝14.2,7.7Hz,1H),3.78(td,J＝7.9,6.4Hz,1H),2.46(dddd,J＝13.9,6.6,2.5,1.5Hz,1H),2.25(ddt,J＝14.0,6.6,2.6Hz,1H),2.15–2.02(m,1H),2.01–1.82(m,2H),1.62(ddd,J＝15.7,12.1,7.2Hz,1H).
13C NMR(101MHz,CDCl3)δ159.40(dd,J＝296.3,293.9Hz),131.40(s),128.36(s),128.29(s),122.91(s),93.50(t,J＝5.8Hz),80.99(dd,J＝8.2,4.0Hz),76.06(dd,J＝34.5,16.6Hz),67.93(s),33.31(d,J＝1.4Hz),30.89(s),25.64(s).
19F NMR(377MHz,CDCl3)δ-78.70(d,J＝14.8Hz),-84.21(d,J＝14.6Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 32
1H NMR(400MHz,CDCl3)δ7.48–7.38(m,2H),7.36–7.28(m,3H),4.76(t,J＝5.8Hz,1H),3.71(dq,J＝9.2,7.1Hz,2H),3.57(dq,J＝9.2,7.0Hz,2H),2.47(dt,J＝5.5,2.1Hz,2H),1.23(t,J＝7.1Hz,6H).
13C NMR(151MHz,CDCl3)δ159.57(t,J＝295.5Hz),131.38(s),128.38(s),128.31(s),122.87(s),100.93(s),93.33(t,J＝5.6Hz),80.90(dd,J＝7.8,4.3Hz),74.86(dd,J＝34.6,17.6Hz),61.90(s),32.21(s),15.27(s).
19F NMR(377MHz,CDCl3)δ-78.58(d,J＝12.5Hz),-83.67(d,J＝12.6Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 33
1H NMR(400MHz,CDCl3)δ7.50–7.42(m,2H),7.36–7.28(m,3H),2.15(dt,J＝7.2,2.3Hz,2H),1.10(s,6H),1.00(s,6H),0.43(t,J＝7.2Hz,1H).
13C NMR(101MHz,CDCl3)δ158.20(dd,J＝295.9,293.0Hz),131.41(s),128.33(s),128.24(s),123.22(s),93.08(t,J＝5.8Hz),81.75(dd,J＝8.4,4.3Hz),79.02(dd,J＝34.4,13.6Hz),31.94(s),23.63(s),23.37(s),21.34(s),16.97(s).
19F NMR(377MHz,CDCl3)δ-80.63(d,J＝18.7Hz),-85.14(d,J＝18.3Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 34
1H NMR(400MHz,CDCl3)δ7.48–7.40(m,2H),7.35–7.28(m,3H),6.80(d,J＝8.0Hz,1H),6.77–6.71(m,2H),3.86(s,3H),3.85(s,3H),2.69–2.59(m,2H),2.21(ddd,J＝7.4,4.5,2.2Hz,2H),1.97–1.86(m,2H).
13C NMR(101MHz,CDCl3)δ158.63(dd,J＝296.1,293.2Hz),148.77(s),147.16(s),134.34(s),131.35(s),128.34(s),128.29(s),122.87(s),120.17(s),111.65(s),111.16(s),93.69–93.44(m),81.00(dd,J＝8.3,4.1Hz),78.34(dd,J＝34.7,14.7Hz),55.86(s),55.69(s),34.40(s),29.47(s),26.39(s).
19F NMR(377MHz,CDCl3)δ-79.70(d,J＝16.8Hz),-84.84(d,J＝16.7Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 35
1H NMR(400MHz,CDCl3)δ7.83–7.75(m,2H),7.56–7.49(m,1H),7.47–7.40(m,4H),7.36–7.29(m,3H),6.81(d,J＝3.9Hz,1H),6.02(d,J＝3.9Hz,1H),4.64–4.51(m,1H),4.38(dt,J＝12.2,7.7Hz,1H),3.62–3.48(m,1H),2.90–2.75(m,1H),2.66–2.54(m,1H),2.50–2.38(m,1H),2.38–2.23(m,1H).
13C NMR(151MHz,CDCl3)δ184.89(s),159.31(dd,J＝297.0,294.1Hz),148.14(s),139.49(s),131.45(s),131.24(s),128.88(s),128.61(s),128.39(s),128.10(s),126.68(s),125.15(s),122.61(s),101.91(s),94.35–94.16(m),80.35(dd,J＝7.9,3.8Hz),47.57(s),36.07(s),33.71(s),31.75(s).
19F NMR(377MHz,CDCl3)δ-78.47(d,J＝13.8Hz),-83.43(d,J＝13.8Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 36
1H NMR(400MHz,CDCl3)δ7.42–7.35(m,2H),7.33–7.27(m,3H),7.15(d,J＝8.5Hz,2H),7.01(d,J＝8.5Hz,2H),2.87(dd,J＝10.6,8.5Hz,1H),2.56(s,2H),1.96(dd,J＝10.7,7.4Hz,1H),1.84–1.76(m,1H),1.41(s,6H).
13C NMR(101MHz,CDCl3)δ163.18–156.88(m),154.48(s),131.24(s),129.55(s),129.41(s),128.33(s),128.28(s),123.62(s),122.92(s),93.50(t,J＝5.8Hz),82.27(dd,J＝7.8,4.4Hz),80.48(t,J＝2.9Hz),75.44(dd,J＝33.7,16.9Hz),60.84(s),40.05(d,J＝1.9Hz),34.93(s),26.27(s),25.86(s).
19F NMR(377MHz,CDCl3)δ-77.71(d,J＝10.7Hz),-82.01(d,J＝9.9Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 37
1H NMR(400MHz,CDCl3)δ7.60(d,J＝8.5Hz,2H),7.43–7.26(m,7H),7.11(d,J＝8.4Hz,2H),6.99(d,J＝8.4Hz,2H),6.24(s,1H),3.66(q,J＝6.7Hz,2H),2.87(t,J＝6.9Hz,2H),2.55(t,J＝1.9Hz,2H),1.40(s,6H).
13C NMR(101MHz,CDCl3)δ166.37(s),160.01(t,J＝296.1Hz),153.58(s),137.56(s),133.71(s),132.92(s),131.18(s),129.24(s),128.73(s),128.32(s),128.26(s),128.20(s),124.24(s),122.88(s),93.46(t,J＝5.8Hz),82.26(dd,J＝7.9,4.4Hz),80.31(t,J＝2.9Hz),75.43(dd,J＝33.5,16.8Hz),41.19(s),39.98(d,J＝1.5Hz),34.81(s),26.22(s).
19F NMR(377MHz,CDCl3)δ-77.69(d,J＝10.5Hz),-82.00(d,J＝10.5Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 38
1H NMR(400MHz,CDCl3)δ7.39(dd,J＝7.7,1.7Hz,2H),7.30–7.19(m,3H),6.99(d,J＝7.5Hz,1H),6.65(d,J＝7.4Hz,1H),6.56(s,1H),3.90(t,J＝6.6Hz,2H),2.28(s,3H),2.17(s,3H),2.12(t,J＝2.1Hz,2H),1.90–1.78(m,2H),1.54–1.45(m,2H),1.03(s,6H).
13C NMR(101MHz,CDCl3)δ159.70(dd,J＝296.5,294.0Hz),157.00(s),136.39(s),131.12(s),130.23(s),128.27(s),128.21(s),123.53(s),123.03(s),120.57(s),111.93(s),93.14(t,J＝5.8Hz),82.88(dd,J＝8.1,4.2Hz),76.11(dd,J＝34.2,14.7Hz),68.44(s),39.02(d,J＝2.0Hz),37.94(s),34.62(t,J＝2.2Hz),26.92(s),24.39(s),21.37(s),15.75(s).
19F NMR(377MHz,CDCl3)δ-78.66(d,J＝13.5Hz),-82.74(d,J＝13.4Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 39
1H NMR(400MHz,CDCl3)δ7.48–7.41(m,2H),7.37–7.28(m,3H),7.17(d,J＝8.0Hz,2H),7.09(d,J＝8.0Hz,2H),3.15–3.02(m,1H),2.46(d,J＝7.1Hz,2H),2.43–2.32(m,2H),1.86(dp,J＝13.4,6.7Hz,1H),1.34(d,J＝7.0Hz,3H),0.91(d,J＝6.6Hz,6H).
13C NMR(101MHz,CDCl3)δ159.18(dd,J＝296.3,293.1Hz),143.09(s),139.67(s),131.46(s),129.14(s),128.33(s),126.66(s),123.03(s),93.59–93.42(m),81.27(dd,J＝8.3,4.1Hz),77.62(dd,J＝42.8,23.3Hz),45.08(s),38.01–37.88(m),36.08(d,J＝1.8Hz),30.25(s),22.42(s),21.03(s).
19F NMR(377MHz,CDCl3)δ-79.71(d,J＝15.9Hz),-84.80(d,J＝16.0Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 40
1H NMR(400MHz,CDCl3)δ7.50–7.38(m,2H),7.36–7.26(m,5H),7.23(dd,J＝11.3,5.7Hz,3H),4.65(d,J＝7.3Hz,1H),4.23–3.98(m,1H),2.89(d,J＝6.4Hz,2H),2.46–2.22(m,2H),1.38(s,9H).
13C NMR(101MHz,CDCl3)δ159.46(dd,J＝297.0,294.6Hz),155.17(s),137.81(s),131.47(s),129.39(s),128.55(s),128.50(s),128.35(s),126.54(s),122.70(s),94.30–94.08(m),81.14–80.78(m),79.34(s),75.79(dd,J＝34.6,15.9Hz),50.88(s),40.15(s),31.34(s),28.33(s).
19F NMR(377MHz,CDCl3)δ-77.79(d,J＝12.4Hz),-83.20(d,J＝12.3Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 41
1H NMR(400MHz,CDCl3)δ7.48–7.39(m,2H),7.31(s,3H),4.17–3.92(m,1H),3.47–3.27(m,2H),2.73–2.46(m,1H),2.37–2.11(m,1H),2.05–1.75(m,4H),1.47(s,9H).
13C NMR(101MHz,CDCl3)δ159.52(dd,J＝296.8,293.7Hz),154.39(s),131.43(s),128.43(s),128.33(s),122.83(s),93.42(dd,J＝10.1,5.6Hz),81.29–80.90(m),79.48(s),76.23(dd,J＝33.5,16.7Hz),56.10(s),46.22(s),31.83(s),30.09(s),28.52(s),22.83(s).
19F NMR(377MHz,CDCl3)δ-78.60(d,J＝13.4Hz),-84.29(d,J＝14.0Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 42
1H NMR(400MHz,CDCl3)δ7.49–7.40(m,2H),7.35–7.27(m,3H),4.73–4.54(m,1H),4.07–3.84(m,1H),2.34(d,J＝4.8Hz,2H),1.43(s,9H),1.22(d,J＝6.7Hz,3H).
13C NMR(101MHz,CDCl3)δ159.55(dd,J＝297.1,294.3Hz),155.08(s),131.45(s),128.49(s),128.30(s),122.74(s),94.05–93.75(m),81.10(dd,J＝7.9,3.7Hz),79.25(s),75.56(dd,J＝35.1,15.5Hz),45.57(s),33.90(s),28.37(s),20.06(s).
19F NMR(377MHz,CDCl3)δ-78.19(d,J＝12.9Hz),-83.81(d,J＝12.7Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 43
1H NMR(400MHz,CDCl3)δ7.51–7.40(m,2H),7.36–7.28(m,3H),4.57(d,J＝8.6Hz,0.75H),4.22(brs,0.19H),3.95(d,J＝5.7Hz,0.82H),3.86(brs,0.18H),2.46–2.15(m,2H),1.80–1.62(m,1H),1.42(s,9H),1.39–1.30(m,2H),0.93(d,J＝6.6Hz,6H).
13C NMR(101MHz,CDCl3)δ159.47(dd,J＝296.7,294.1Hz),155.22(s),131.36(s),128.39(s),128.25(s),122.75(s),93.83(t,J＝6.0Hz),81.41–81.09(m),79.07(s),75.47(dd,J＝35.0,14.7Hz),47.79(s),43.17(s),32.61(s),28.31(s),24.82(s),22.98(s),22.16(s).
19F NMR(377MHz,CDCl3)δ-78.12(d,J＝13.5Hz),-83.78(d,J＝13.5Hz).
Analytical data for 1, 1-difluoro-substituted 1, 3-eneyne 44
1H NMR(400MHz,CDCl3)δ7.46(dd,J＝6.6,2.9Hz,2H),7.37–7.28(m,3H),4.71(d,J＝8.8Hz,1H),4.03–3.84(m,1H),2.65–2.49(m,2H),2.47–2.28(m,2H),2.10(s,3H),1.95–1.73(m,2H),1.42(s,9H).
13C NMR(101MHz,CDCl3)δ159.52(dd,J＝297.4,294.5Hz),155.29(s),131.45(s),128.56(s),128.33(s),122.62(s),94.14(dd,J＝8.8,4.6Hz),81.02–80.78(m),79.43(s),75.40(dd,J＝33.2,17.2Hz),49.21(s),33.71(s),32.28(s),30.75(s),28.34(s),15.60(s).
19F NMR(377MHz,CDCl3)δ-77.73(d,J＝12.7Hz),-83.43(d,J＝12.6Hz).
The foregoing embodiments have described the technical solutions and advantages of the present invention in detail, and it should be understood that the foregoing embodiments are merely illustrative of the present invention and are not intended to limit the invention, and any modifications, additions, substitutions and the like that fall within the principles of the present invention should be included in the scope of the invention.
Claims (10)
1. A process for the preparation of a1, 1-difluoro-substituted-1, 3-eneyne compound, comprising: reacting a compound of formula (1) with a compound of formula (2) in the presence of a photocatalyst and a base under blue light irradiation to produce a1, 1-difluoro-1, 3-eneyne compound of formula (3):
Wherein R 1 is selected from substituted or unsubstituted C1-C10 chain alkyl, substituted or unsubstituted C3-C10 cyclic alkyl, substituted or unsubstituted aryl, heteroaryl;
The compound of formula (2) is a carboxylic acid;
the photocatalyst is selected from metallic iridium photocatalyst, metallic ruthenium photocatalyst and carbazole photocatalyst.
2. The process of claim 1, wherein the compound of formula (2) is a primary carboxylic acid, a secondary carboxylic acid, a tertiary carboxylic acid, a natural amino acid, or a pharmaceutical-derived carboxylic acid.
3. The process according to claim 1, wherein the aromatic hydrocarbon is selected from the group consisting of a substituted or unsubstituted C1-C10 chain alkyl group, a substituted or unsubstituted C3-C10 cyclic alkyl group, a substituted or unsubstituted C3-C10 heterocycloalkyl group, a substituted or unsubstituted C1-C10 alkoxy group, a substituted or unsubstituted aryl group, and a heteroaryl group.
4. A process according to claim 3, wherein in R 1, the substituents on the substituted chain alkyl groups are halogen and/or ester groups; the substituent on the substituted cyclic alkyl group is a cyclic alkyl group; the substituent on the substituted aryl and heteroaryl is halogen, substituted or unsubstituted C1-C6 alkoxy and substituted or unsubstituted C1-C6 alkyl;
In R 2, the substituent on the substituted alkyl is halogen and/or ester; the substituent on the substituted alkoxy is halogen and/or ester; the substituent on the substituted aryl and heteroaryl is halogen substituted or unsubstituted C1-C6 alkyl, halogen substituted or unsubstituted C1-C6 alkoxy, halogen and/or ester, and the substituent on the substituted aryl and heteroaryl is halogen, substituted or unsubstituted C1-C6 alkoxy and substituted or unsubstituted C1-C6 alkyl.
5. A process according to claim 3, wherein the aryl group is phenyl or naphthyl; heteroaryl is benzothienyl.
6. The process according to claim 1, wherein the compound of formula (1) is selected from:
7. the process according to claim 1, wherein the compound of formula (2) is selected from:
8. The method of claim 1, wherein the catalyst is selected from the group consisting of:
9. the method of claim 1, wherein the blue light has a wavelength of 390-440 nm.
10. The method according to claim 1, wherein the base is an organic base or an inorganic base; the organic base is at least one of triethylamine and diisopropylethylamine; the inorganic base is at least one of potassium carbonate, potassium phosphate, potassium hydroxide, sodium hydroxide and dipotassium hydrogen phosphate.
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