Benzodifluorocyclohexane bridged ring compound as well as preparation method and application thereof

Abstract

The invention relates to the technical field of organic synthesis, in particular to a benzodifluorocyclohexane bridged ring compound as well as a preparation method and application thereof, the molecular structural formula of the benzodifluorocyclohexane bridged ring compound is shown as G: # imgabs0 #, and R1, R2, R3, R4 and R5 are respectively any one of hydrogen atoms, alkyl, aryl, alkoxy, ester groups, aldehyde groups, cyano groups and halogens, are not hydrogen atoms at the same time, and can be the same or different. The benzodifluorocyclohexane bridged ring compound disclosed by the invention is a novel compound, is an important organic intermediate, can be used for synthesizing various medicines, and has a wide application prospect. In addition, complex bioactive molecules and drug molecules can be subjected to later modification. According to the preparation method disclosed by the invention, 4 + 2 cyclization reaction of naphthalene A and difluoroolefin B is realized. The invention provides a simple and efficient method for synthesizing the benzodifluorocyclohexane bridged ring compound.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a benzodifluorocyclohexane bridge ring compound, a preparation method and application thereof. Background Art

[0002] Benzocyclohexane cyclized compounds play an important role as an important parent framework in bioactive molecules. [a) A. Thuillier, Tetrahedron 1980, 36, 2497-2503; b) E.-E. Kamal, Molecules 2016, 21, 1-6] Fluorine atoms will enhance the lipophilicity of the molecule, making it easier for drug molecules to enter cells. Fluorine atoms can also enhance the biological metabolic stability of drug molecules and improve the utilization rate of drugs. Currently, one-third of small molecule drugs on the market contain fluorine atoms, so introducing fluorine atoms into the structure has key scientific significance and theoretical value. [a) WK Hagmann, J. Med. Chem. 2008, 51, 4359; b) F. Diederich Science 2007, 217, 1881] Therefore, benzodifluorocyclohexane bridged ring compounds have potential important application value in drug molecules. However, due to the lack of synthetic methods, there are very few reports of such molecules in the literature. The few examples of 4+2 cyclization reactions of naphthalene and olefins require naphthalene rings activated by electron-withdrawing groups and the parent structure containing fluorine has not been reported [a) MK Brown, Chem. Sci. 2022, 13, 13582-13587; b) B. Thorsten, GK Murphy, Chem. Commun. 2019, 55, 14821-14824]

[0003] Since benzodifluorocyclohexane bridged ring compounds are difficult to obtain, there are few reports on their synthesis and application. Summary of the invention

[0004] One of the purposes of the present invention is to provide a benzodifluorocyclohexane bridged ring compound, which is an important organic intermediate and can be used for the synthesis of various drugs with broad application prospects. In addition, it can also be used for post-modification of complex molecules and drug molecules.

[0005] The second object of the present invention is to provide a method for preparing a benzodifluorocyclohexane bridge ring compound, which has a simple preparation process, is easy to adjust, and has good substrate universality and functional group tolerance.

[0006] The third object of the present invention is to provide an application of a benzodifluorocyclohexane bridged ring compound.

[0007] The scheme adopted by the present invention to achieve one of the purposes is: a benzodifluorocyclohexane bridged ring compound, whose molecular structure is shown in G:

[0008]

[0009] Among them, R1, R2, R3, R4, and R5 are each a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, an ester group, an aldehyde group, a cyano group, or a halogen group, but they are not all hydrogen atoms at the same time, and they may be the same or different.

[0010] Preferably, the alkyl group has 1-20 carbon atoms and is a straight chain structure, a cyclic structure or a branched structure; the alkyl group carries one or more substituents. When there are multiple substituents, the substituents may be the same or different and the positions may be the same or different.

[0011] Preferably, the aryl group carries one or more substituents; when having multiple substituents, the substituents may be the same or different.

[0012] The scheme adopted by the present invention to achieve the second purpose is: a method for preparing the benzodifluorocyclohexane bridged ring compound: naphthalene A and difluoroolefin B, a catalyst, and an organic solvent are mixed, and the mixture is stirred and reacted under light and at a temperature of -78°C to 180°C, followed by separation and purification to obtain the benzodifluorocyclohexane bridged ring compound G.

[0013] Preferably,

[0014] The molecular structural formula of the naphthalene A is:

[0015] The molecular structural formula of the difluoroolefin B is:

[0016] Preferably, the catalyst is any one of an Ir-type photocatalyst, a Ru-type photocatalyst, a carbazole-type photocatalyst, an acridine-type photocatalyst, and Solvent Red 43.

[0017] The catalyst is tris[2-phenylpyridine-C2,N]iridium(III), bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium di(hexafluorophosphate), bis[2-(2,4-difluorophenyl)-5-methylpyridine][2,2'-bi(tetra-tert-butylpyridine)]iridium di(hexafluorophosphate), bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bipyridine]iridium di(hexafluorophosphate), [2,2'-bi(4-tert-butylpyridine)]bis[2-(2,4-difluorophenyl)pyridine]iridium(III)hexafluorophosphate, (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium (III) hexafluorophosphate, bis(2-methyl-3-phenylpyrazine-C2,N)iridium acetylacetonate, bis(2,3-diphenylpyrazine-C2,N)iridium acetylacetonate, bis(2,3-diphenylquinoxaline)iridium acetylacetonate, bis(2-phenylpyrimidine-C2,N)iridium acetylacetonate, (2,2'-bipyridine)bis[2-(4-fluorophenyl)pyridine]iridium(III) hexafluorophosphate, (2,2'-bipyridine)bis[2-(2,4-difluorophenyl)pyridine]iridium(III) hexafluorophosphate, (2,2'-bipyridine)bis[2-(4-tert-butylphenyl)pyridine]iridium(III) hexafluorophosphate, (2-2'-bipyridine)bis[2-(4-tert-butylphenyl)pyridine]iridium(III) hexafluorophosphate ]iridium(III) hexafluorophosphate, (1,10-phenanthroline)bis[2-(4-tert-butylphenyl)pyridine]iridium(III) hexafluorophosphate, tris(2-(4-fluorophenyl)pyridine)iridium, tris[2-(4,6-difluorophenyl)pyridine-C2,N]iridium(III), bis[2-(3-tert-butylphenyl)-4-tert-butylpyridine][2,2`-bi(4-tert-butylpyridine)]iridium(III) hexafluorophosphate, dichlorotetrakis(2-(2-pyridyl)phenyl)diiridium(III), tris(2-(4-trifluoromethylphenyl)pyridine)iridium, [2,2'-bi(4-tert-butylpyridine)]bis[2-(4-fluorophenyl)pyridine]iridium(III) hexafluorophosphate, rhodamine 6G, tris(1,10- Phenanthroline) ruthenium (II) bis(hexafluorophosphate), tris(4,4'-dimethyl-2,2'-bipyridyl) ruthenium (III) (hexafluorophosphate), tris(2,2'-bipyrazine) ruthenium di(hexafluorophosphonate), tris(2,2'-bipyridyl) ruthenium di(hexafluorophosphate), tris(2,2'-bipyridyl) ruthenium di(perchlorate), tris(2,2'-bipyridyl) Ruthenium di(tetrafluoroborate), tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate, 9-mesityl-10-phenylacridine-10-tetrafluoroborate, 2,3,5,6-tetra(9-carbazolyl)-terephthalonitrile, 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile (4CzIPN), derivatives of 4CzIPN, tris(2,Any one of 2'-bipyridyl)ruthenium(II) chloride hexahydrate and Solvent Red 43.

[0018] Preferably, the organic solvent is methanol, ethanol, isopropanol, tert-butyl alcohol, tetrahydrofuran, 2-methyltetrahydrofuran, ether, dimethyl ether, methyl tert-butyl ether, 1,4-epoxyhexadecane, 1,3-epoxyhexadecane, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, C 4-12 Saturated alkanes, C 3-12 Fluorinated or chlorinated alkanes, benzene, toluene, xylene, trimethylbenzene, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, acetone, N-methylpyrrolidone, acetonitrile, C 3-12 At least one of the saturated alkyl nitriles.

[0019] Preferably, the molar ratio of naphthalene A to difluoroolefin B is 1-2:1; the amount of the catalyst is 0.15% to 5% of the molar amount of difluoroolefin B, and the concentration of difluoroolefin B in the mixed solution is between 0.1M and 1M.

[0020] The illumination process may adopt any one of white light, blue light, purple light, green light, sunlight or other illumination modes.

[0021] After the reaction is completed, the reaction product is subjected to post-treatment, including purification methods such as suction filtration, concentration, recrystallization and column chromatography, which are all conventional methods in the art.

[0022] The solution adopted by the present invention to achieve the third purpose is: the benzodifluorocyclohexane bridge ring compound is used as an organic intermediate in drug synthesis or in the later modification of complex molecules and drug molecules.

[0023] The method of the present invention realizes the synthesis of benzodifluorocyclohexane bridged ring compound for the first time by reacting simple naphthalene A and difluoroolefin B under illumination, can realize the synthesis of benzodifluorocyclohexane bridged ring compound in one step, and can be applied to synthesize various substituted benzodifluorocyclohexane bridged ring compounds, and has good substrate universality and functional group tolerance. The synthesized benzodifluorocyclohexane bridged ring compound is an important organic intermediate, which can be used for the synthesis of various drugs and has a wide range of application prospects. In addition, complex molecules and drug molecules can also be modified later.

[0024] The present invention has the following advantages and beneficial effects:

[0025] (1) The benzodifluorocyclohexane bridged ring compound of the present invention is a novel compound and an important organic intermediate, which can be used for the synthesis of various drugs and has a wide application prospect. In addition, it can also be used for post-modification of complex biologically active molecules and drug molecules.

[0026] (2) The preparation method of the present invention realizes the 4+2 cyclization reaction of naphthalene A and difluoroolefin B. A simple and efficient method is provided for synthesizing benzodifluorocyclohexane bridged ring compounds. The method can be applied to synthesize various substituted benzodifluorocyclohexane bridged ring compounds, has good substrate universality and functional group tolerance, and is compatible with various functional groups such as ester groups, halogens, and carbonyl groups. Various straight-chain or branched alkyl groups can also complete the reaction.

[0027] (3) The preparation method of the present invention is carried out under a photocatalytic condition, and the reaction conditions are simple, efficient and mild. DETAILED DESCRIPTION

[0028] For a better understanding of the present invention, the following examples are provided to further illustrate the present invention, but the present invention is not limited to the following examples.

[0029] Embodiment 1:

[0030]

[0031] In a glove box, add A (51.2 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol) and fac-(dFppy) 3 (3 mg, 2 mol%), and dry DCM (2 mL) to a photoreaction tube that is dry and equipped with a magnetic stirrer. Seal the photoreaction tube, take it out of the glove box, and then irradiate it with a 6W purple 400nm LED lamp. The reaction mixture is stirred at room temperature for 12 hours. Then turn off the purple lamp and concentrate the reaction mixture under reduced pressure. The crude product is purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (300 / 1-100 / 1, v / v) to obtain the target compound G1 (white oily liquid 61.6 mg, yield 95%).

[0032] 11H NMR (600 MHz, CDCl3, 25 °C) δ 7.38–7.33 (m, 2H, H+H’), 7.25–7.17 (m, 4H, H+H’), 7.17–7.12 (m, 1H, H), 6.92–6.88 (m, 1H, H+H’), 6.67–6.59 (m, 1H, H+H’), 6.52 (dd, J=8.4, 1.5 Hz, 1H, H), 4.32–4.23 (m, 1H, H+H’), 4.13–4.08 (m, 1H, H’), 4.00–3.94 (m, 1H, H), 3.39 (ddd, J=23.8, 7.8, 2.2 Hz, 1H, H), 3.24 (ddd, J=22.8, 7.8, 1.9 Hz, 1H, H’), 1.31 (s, 9H, H’), 1.24 (s, 9H, H). 13 13C NMR (151 MHz, CDCl3, 25 °C) δ 150.3 (C’), 150.0 (C), 144.2 (C’), 140.4 (C), 139.2 (C), 138.8 (d, J=6.7 Hz, C), 138.7 (d, J=7.0 Hz, C), 135.6 (C’), 133.8 (d, J=5.5 Hz, C’), 133.5 (d, J=4.7 Hz, C), 132.2 (d, J=5.8 Hz, C’), 132.0 (d, J=6.2 Hz, C), 129.2 (C), 128.7 (C’), 127.0 (C’), 126.6 (C), 126.5 (C’), 126.2 (C), 126.1 (C’), 125.9 (C), 125.3 (C’), 125.2 (dd, J=256.7, 253.8 Hz, C+C’), 124.9 (C), 123.6 (C’), 122.8 (C), 55.3 (dd, J=24.9, 20.9 Hz, C’), 54.3 (dd, J=24.7, 20.8 Hz, C), 50.5 (dd, J=26.6, 24.4 Hz, C’), 50.0 (t, J=25.6 Hz, C), 47.6 (d, J=5.5 Hz, C), 46.6 (d, J=4.9 Hz, C’), 34.6 (C’), 34.5 (C), 31.5 (C’), 31.4 (C). 19 19F NMR (565 MHz, CDCl3, 25 °C) δ

[0033] 83.2–84.3 (m, 1F, F+F’), 93.8–94.4 (m, 1F, F), 94.6–95.1 (m, 1F, F’).

[0034] Example 2:

[0035]

[0036] In a glove box, A (51.2 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol) and [Ir(dF(CF3)2(dtbbpy)]PF6 (4.6 mg, 2 mol%) and dry DCM (2 mL) were added to a dry photoreaction tube equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The purple lamp was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (300 / 1-100 / 1, v / v) to obtain the target compound G1 (white oily liquid 55.1 mg, yield 85%).

[0037] 1 H NMR (600MHz, CDCl3, 25℃) δ7.38–7.33(m,2H,H+H'),7.25–7.17(m,4H,H+H'),7.17–7.12(m ,1H,H),6.92–6.88(m,1H,H+H'),6.67–6.59(m,1H,H+H'),6.52(dd,J=8.4,1.5Hz,1H,H), 4.32–4.23(m,1H,H+H'),4.13–4.08(m,1H,H'),4.00–3.94(m,1H,H),3.39(ddd,J=23.8,7 .8,2.2Hz,1H,H),3.24(ddd,J=22.8,7.8,1.9Hz,1H,H'),1.31(s,9H,H'),1.24(s,9H,H). 13C NMR (151MHz, CDCl3, 25℃) δ150.3(C'),150.0(C),144.2(C'),140.4(C),139 .2(C),138.8(d,J=6.7Hz,C),138.7(d,J=7.0Hz,C),135.6(C'),133.8(d,J =5.5Hz,C'),133.5(d,J=4.7Hz,C),132.2(d,J=5.8Hz,C'),132.0(d,J=6.2 Hz,C),129.2(C),128.7(C'),127.0(C'),126.6(C),126.5(C'),126.2(C),1 26.1(C'),125.9(C),125.3(C'),125.2(dd,J=256.7,253.8Hz,C+C'),124. 9(C),123.6(C'),122.8(C),55.3(dd,J=24.9,20.9Hz,C'),54.3(dd,J=24.7 ,20.8Hz,C),50.5(dd,J=26.6,24.4Hz,C'),50.0(t,J=25.6Hz,C),47.6(d, J=5.5Hz,C),46.6(d,J=4.9Hz,C'),34.6(C'),34.5(C),31.5(C'),31.4(C). 19 F NMR (565MHz, CDCl3, 25℃)δ

[0038] 83.2–84.3(m,1F,F+F'),93.8–94.4(m,1F,F),94.6–95.1(m,1F,F').

[0039] Embodiment 3:

[0040]

[0041] In a glove box, add A (51.2 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol) and fac-(dFppy) 3 (3 mg, 2 mol%), and dry toluene (1 mL) to a photoreaction tube that is dried and equipped with a magnetic stirrer. Seal the photoreaction tube, take it out of the glove box, and then irradiate it with a 6W purple 400nm LED lamp. The reaction mixture is stirred at room temperature for 12 hours. Then turn off the purple lamp and concentrate the reaction mixture under reduced pressure. The crude product is purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (300 / 1-100 / 1, v / v) to obtain the target compound G1 (white oily liquid 44.7 mg, yield 69%).

[0042] 1 1H NMR (600 MHz, CDCl3, 25 °C) δ 7.38–7.33 (m, 2H, H+H’), 7.25–7.17 (m, 4H, H+H’), 7.17–7.12 (m, 1H, H), 6.92–6.88 (m, 1H, H+H’), 6.67–6.59 (m, 1H, H+H’), 6.52 (dd, J = 8.4, 1.5 Hz, 1H, H), 4.32–4.23 (m, 1H, H+H’), 4.13–4.08 (m, 1H, H’), 4.00–3.94 (m, 1H, H), 3.39 (ddd, J = 23.8, 7.8, 2.2 Hz, 1H, H), 3.24 (ddd, J = 22.8, 7.8, 1.9 Hz, 1H, H’), 1.31 (s, 9H, H’), 1.24 (s, 9H, H). 13 13C NMR (151 MHz, CDCl3, 25 °C) δ 150.3 (C’), 150.0 (C), 144.2 (C’), 140.4 (C), 139.2 (C), 138.8 (d, J = 6.7 Hz, C), 138.7 (d, J = 7.0 Hz, C), 135.6 (C’), 133.8 (d, J = 5.5 Hz, C’), 133.5 (d, J = 4.7 Hz, C), 132.2 (d, J = 5.8 Hz, C’), 132.0 (d, J = 6.2 Hz, C), 129.2 (C), 128.7 (C’), 127.0 (C’), 126.6 (C), 126.5 (C’), 126.2 (C), 126.1 (C’), 125.9 (C), 125.3 (C’), 125.2 (dd, J = 256.7, 253.8 Hz, C+C’), 124.9 (C), 123.6 (C’), 122.8 (C), 55.3 (dd, J = 24.9, 20.9 Hz, C’), 54.3 (dd, J = 24.7, 20.8 Hz, C), 50.5 (dd, J = 26.6, 24.4 Hz, C’), 50.0 (t, J = 25.6 Hz, C), 47.6 (d, J = 5.5 Hz, C), 46.6 (d, J = 4.9 Hz, C’), 34.6 (C’), 34.5 (C), 31.5 (C’), 31.4 (C). 19 19F NMR (565 MHz, CDCl3, 25 °C) δ

[0043] 83.2–84.3 (m, 1F, F+F’), 93.8–94.4 (m, 1F, F), 94.6–95.1 (m, 1F, F’).

[0044] Example 4:

[0045]

[0046] In a glove box, A (51.2 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W blue 460 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The blue light was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (300 / 1-100 / 1, v / v) to obtain the target compound G1 (white oily liquid 50.5 mg, yield 78%).

[0047] 1 H NMR (600MHz, CDCl3, 25℃) δ7.38–7.33(m,2H,H+H'),7.25–7.17(m,4H,H+H'),7.17–7.12(m ,1H,H),6.92–6.88(m,1H,H+H'),6.67–6.59(m,1H,H+H'),6.52(dd,J=8.4,1.5Hz,1H,H), 4.32–4.23(m,1H,H+H'),4.13–4.08(m,1H,H'),4.00–3.94(m,1H,H),3.39(ddd,J=23.8,7 .8,2.2Hz,1H,H),3.24(ddd,J=22.8,7.8,1.9Hz,1H,H'),1.31(s,9H,H'),1.24(s,9H,H). 13C NMR (151MHz, CDCl3, 25℃) δ150.3(C'),150.0(C),144.2(C'),140.4(C),139 .2(C),138.8(d,J=6.7Hz,C),138.7(d,J=7.0Hz,C),135.6(C'),133.8(d,J =5.5Hz,C'),133.5(d,J=4.7Hz,C),132.2(d,J=5.8Hz,C'),132.0(d,J=6.2 Hz,C),129.2(C),128.7(C'),127.0(C'),126.6(C),126.5(C'),126.2(C),1 26.1(C'),125.9(C),125.3(C'),125.2(dd,J=256.7,253.8Hz,C+C'),124. 9(C),123.6(C'),122.8(C),55.3(dd,J=24.9,20.9Hz,C'),54.3(dd,J=24.7 ,20.8Hz,C),50.5(dd,J=26.6,24.4Hz,C'),50.0(t,J=25.6Hz,C),47.6(d, J=5.5Hz,C),46.6(d,J=4.9Hz,C'),34.6(C'),34.5(C),31.5(C'),31.4(C). 19 F NMR (565MHz, CDCl3, 25℃)δ

[0048] 83.2–84.3(m,1F,F+F'),93.8–94.4(m,1F,F),94.6–95.1(m,1F,F').

[0049] Embodiment 5:

[0050]

[0051] In a glove box, A (51.2 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W blue 460 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The blue light was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (300 / 1-100 / 1, v / v) to obtain the target compound G1 (white oily liquid 50.5 mg, yield 78%).

[0052] 1 H NMR(600MHz,CDCl3,25℃)δ7.41–7.39(m,1H,H+H’),7.29–7.25(m,1H,H+H’),7.24–7.20(m,2H,H+H’),7.17(dd,J=7.2,1.3Hz,2H,H’),6.94–6.87(m,2H,H+H’),6.72–6.62(m,2H,H+H’),6.49(dd,J=8.7,1.6Hz,2H,H),4.35–4.27(m,1H,H+H’),4.12–4.08(m,1H,H’),3.96–3.91(m,1H,H),3.82(s,3H,H’),3.74(s,3H,H),3.40(ddd,J=23.9,7.7,2.2Hz,1H,H),3.23(ddd,J=22.9,7.6,1.8Hz,1H,H’). 13 C NMR(151MHz,CDCl3,25℃)δ159.0(C’),158.8(C),144.1(C’),140.3(C),138.9(C),138.6(dd,J=7.1,4.7Hz,C+C’),135.5(C’),132.3(d,J=6.0Hz,C’),131.9(d,J=6.1Hz,C),130.6(d,J=2.0Hz,C),130.1(C’),129.0(d,J=5.4Hz,C’),128.7(d,J=4.7Hz,C),128.0(C’),126.9(C),126.6(C+C’),126.5(C+C’),126.2(C’),126.1(C),126.1(C’),125.9(C),125.1(dd,J=256.8,251.9Hz,C+C’),122.8(C+C’),113.8(C’),113.4(C),55.4(C’),55.2(C),54.9(dd,J=25.0,20.9Hz,C’),54.0(dd,J=24.8,20.8Hz,C),50.4(dd,J=24.8,20.8Hz,C’),50.0(t,J=25.7Hz,C),48.1(d,J=5.6Hz,C),46.9(d,J=4.9Hz,C’). 19FNMR (565MHz, CDCl3, 25℃) δ-83.4–-83.9(m,1F,F),-84.0–-84.5(m,1F,F'),-9 4.2(ddd,J=225.8,8.1,4.4Hz,1F,F),-94.9(ddt,J=223.3,8.2,4.3Hz,1F,F').

[0053] Embodiment 6:

[0054]

[0055] In a glove box, A (76.8 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. Then the blue light was turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (300 / 1-100 / 1, v / v) to obtain the target compound G3 (colorless liquid 55.5 mg, yield 85%). 1 HNMR (600MHz, CDCl3, 25℃) δ8.00(d,J=8.3Hz,2H,H'),7.81(d,J=8.4Hz,2H,H),7.42–7.39(m,1H,H+H'),7.35(d,J=8.2Hz,2H, H'),7.30–7.24(m,1H,H+H'),7.23–7.20(m,2H,H),7.12(dd,J=7.3,1.2Hz,1H),6.91(ddd,J=7.5,6.1,1.4Hz,2H,H'),6.72–6 .65(m,1H,H+H'),6.62(dd,J=8.4,1.6Hz,2H,H),4.34–4.29(dqd,J=16.6,5.8,1.3Hz,1H,H+H'),4.14–4.12(m,1H,H'),3.96– 3.94(m,1H,H),3.92(s,3H,H'),3.87(s,3H,H),3.49(ddd,J=23.3,7.4,2.2Hz,1H,H),3.33(ddd,J=22.4,7.6,1.8Hz,1H,H'). 13C NMR (151MHz, CDCl3, 25℃) δ167.0(C),167.0(C'),143.6(C'),142.1(d,J=5.4Hz,C'),141.8(d,J=4.3Hz,C),139.7(C),138.6(C),138.5–138.4(m,C +C'),135.2(C'),132.6(d,J=5.9Hz,C'),132.4(d,J=6.3Hz,C),129.6(C ),129.6(C'),129.3(C'),129.2(C),129.1(C),129.1(C'),127.1(C'),12 6.8(C),126.8(C),126.4(C'),126.2(C'),126.1(C),126.0(C),125.1(d d,J=256.6,251.9Hz,C+C'),122.94(C'),55.6(dd,J=25.1,20.7Hz,C'),5 4.7(dd,J=25.3,20.4Hz,C),52.2(C'),52.2(C),50.4(dd,J=25.0,20.2H z, C'), 49.9 (t, J = 25.4Hz, C), 47.6 (d, J = 5.1Hz, C), 46.2 (d, J = 4.6Hz, C'). 19 FNMR (565MHz, CDCl3, 25℃) δ-82.6–-83.1(m,1F,F),-83.4–-83.9(m,1F,F’),-94.2–-95.0(m,1F,F+F’).

[0056] Embodiment 7:

[0057]

[0058] In a glove box, add A (51.2 mg, 0.4 mmol, 2 equiv.), B (43.4 mg, 0.2 mmol) and fac-(dFppy) 3 (3 mg, 2 mol%), and dry DCM (2 mL) to a photoreaction tube that is dried and equipped with a magnetic stirrer. Seal the photoreaction tube, take it out of the glove box, and then irradiate it with a 6W purple 400nm LED lamp. The reaction mixture is stirred at room temperature for 12 hours. Then turn off the blue light and concentrate the reaction mixture under reduced pressure. The crude product is purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (300 / 1-100 / 1, v / v) to obtain the target compound G4 (colorless liquid 68.6 mg, yield 99%).

[0059] 11H NMR (600 MHz, CDCl3, 25 °C) δ 7.46–7.43 (m, 1H, H’), 7.38 (d, J = 7.1 Hz, 1H, H+H’), 7.27–7.18 (m, 4H, H+H’), 7.13 (dd, J = 14.3, 7.7 Hz, 1H, H+H’), 6.90–6.85 (m, 1H, H+H’), 6.69–6.62 (m, 1H, H+H’), 6.41–6.38 (m, 1H, H+H’), 4.32–4.29 (m, 1H, H’), 4.29–4.26 (m, 1H, H), 4.09–4.05 (m, 1H, H’), 3.92–3.87 (m, 1H, H), 3.38 (ddd, J = 23.4, 7.4, 2.2 Hz, 1H, H), 3.21 (ddd, J = 22.5, 7.5, 1.8 Hz, 1H, H’). 13 13C NMR (151 MHz, Chloroform-d) δ 143.7 (C’), 139.8 (C), 138.6 (C), 138.5 (C), 138.4 (C’), 135.9 (d, J = 5.6 Hz, C’), 135.6 (d, J = 4.4 Hz, C), 135.2 (C’), 132.6 (d, J = 5.8 Hz, C’), 132.2 (d, J = 6.3 Hz, C), 131.5 (C’), 131.3 (C’), 131.2 (C’), 131.1 (C), 130.7 (C), 127.1 (C’), 126.7 (C+C’), 126.3 (C’), 126.1 (C+C’), 126.0 (C), 125.3 (dd, J = 256.8, 251.2 Hz, C’), 125.0 (dd, J = 256.9, 251.3 Hz, C’), 122.9 (C’), 121.5 (C’), 121.5 (C), 55.1 (dd, J = 25.1, 20.8 Hz, C’), 54.2 (dd, J = 25.1, 20.6 Hz, C), 50.6–50.1 (m, C’), 49.9 (t, J = 25.5 Hz, C), 47.7 (d, J = 5.2 Hz, C), 46.4 (d, J = 4.8 Hz, C’). 19 19F NMR (565 MHz, CDCl3, 25 °C) δ -83.3 (ddt, J = 225.9, 23.1, 3.5 Hz, 1F, F), -83.7–-84.2 (m, 1F, F’), -94.2–-95.0 (m, 1F, F+F’).

[0060] Example 8:

[0061]

[0062] In a glove box, A (102.4 mg, 0.8 mmol, 4 equiv.), B (42 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The blue light was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (300 / 1-100 / 1, v / v) to obtain the target compound G5 (colorless liquid 47.4 mg, yield 70%).

[0063] 1 H NMR (600MHz, CDCl3, 25℃) δ7.41(d,J=7.3Hz,1H,H),7.37–7.33(m,2H,H+H'),7.30–7.28(m,1H,H') ,7.24–7.14(m,4H,H+H'),7.10–7.07(m,1H,H),6.93(dd,J=7.5,5.9Hz,1H,H'),6.89–6.86(m,1H, H),6.63–6.59(m,1H,H),6.45–6.41(m,1H,H'),4.37–4.34(m,1H,H),4.32–4.29(m,1H,H'),4.26– 4.20(m,1H,H+H'),1.53–1.50(m,3H,H),1.34(s,9H,H'),1.26(s,9H,H),0.97(d,J=5.1Hz,3H,H). 1313C NMR (151 MHz, CDCl3, 25 °C) δ 149.2 (C’), 148.7 (C), 142.6 (C’), 141.5 (C), 140.4 (d, J = 6.8 Hz, C’), 139.7 (d, J = 6.5 Hz, C), 139.3 (d, J = 7.4 Hz, C’), 139.1 (C), 138.2 (d, J = 7.2 Hz, C), 136.9 (C’), 131.5 (d, J = 6.4 Hz, C), 131.2 (d, J = 6.0 Hz, C’), 127.6 (d, J = 2.6 Hz, C), 127.6 (d, J = 2.1 Hz, C’), 126.6 (C’), 126.4 (C), 126.3 (C’), 126.2 (C), 126.0 (C), 125.7 (C’), 125.5 (C), 125.3 (dd, J = 256.8, 251.9 Hz, C), 125.2 (C’), 124.9 (dd, J = 256.9, 251.4 Hz, C’), 124.7 (C’), 124.3 (C), 53.0–52.7 (m, C’), 52.5–52.2 (m, C), 51.2 (t, J = 27.1 Hz, C), 50.8–50.4 (m, C + C’), 34.5 (C’), 34.3, 31.5 (C’), 31.4, 30.3 (d, J = 15.4 Hz, C), 29.4 (d, J = 15.3 Hz, C’). 19 19F NMR (565 MHz, CDCl3, 25 °C) δ -82.4 (d, J = 223.5 Hz, 1F, F), -83.9 (d, J = 221.4 Hz, 1F, F’), -91.5 (dq, J = 223.6, 5.5 Hz, 1F, F), -92.8 (dp, J = 221.5, 5.1 Hz, 1F, F’).

[0064] Example 9:

[0065]

[0066] In a glove box, A (68 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a dry photoreaction tube equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. Then the blue light was turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (30 / 1-10 / 1, v / v) to obtain the target compound G6 (colorless liquid 49.7 mg, yield 73%). 1 HNMR (600MHz, CDCl3, 25℃) δ7.74–7.70(m,1H,H+H'),7.48–7.45(m,1H,H+H'),7.31–7.28(m,1H,H+H'),7.25–7. 22(m,1H,H+H'),7.18(dd,J=7.4,1.2Hz,1H,H),7.11–7.07(m,1H,H),6.89–6.86(m,1H,H),6.70–6.66(m,1H,H+H '),6.46–6.43(m,1H,H+H'),5.07–5.03(m,1H,H+H'),4.28–4.24(m,1H,H'),4.08–4.05(m,1H,H),3.81(s,3H,H '),3.73(s,3H,H),3.40(ddd,J=23.6,7.4,2.2Hz,1H,H),3.32–3.27(m,1H,H'),2.39(s,3H,H'),2.36(s,3H,H). 13C NMR (151MHz, CDCl3, 25℃) δ194.0(C),193.7(C'),159.1(C'),159.1(C),1 47.5(C),145.2(C),145.1(C),145.0(C),142.5(C'),138.6(C),137.6(d, J=7.0Hz,C),137.5(d,J=7.5Hz,C'),130.7(d,J=2.1Hz,C),129.8(C'),12 8.0(d,J=5.7Hz,C'),127.6(d,J=4.3Hz,C),127.4(C'),127.3(C),127.0( C),126.9(C'),126.7(C'),126.4(C),124.7(dd,J=256.9,252.1Hz,C'), 124.3(dd,J=256.7,251.8Hz,C),123.2(C+C'),114.0(C'),113.5(C),55. 4(C'),55.3(C),55.1–54.8(m,C'),52.9(dd,J=26.1,21.1Hz,C),48.7(C' ),48.7(C),47.9(t,J=26.7Hz,C'),47.7–47.3(m,C),25.5(C'),25.3(C). 19 F NMR (565MHz, CDCl3, 25℃) δ-85.0 (ddt, J=227.6, 23.5, 4.0Hz, 1F, F), -86.2–-86 .7(m,1F,F'),-95.3–-95.8(m,1F,F),-96.2(ddt,J=226.0,8.0,4.1Hz,1F,F').

[0067] Embodiment 10:

[0068]

[0069] In a glove box, add A (68 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy) 3 (3 mg, 2 mol%), and dry DCM (2 mL) to a photoreaction tube that is dried and equipped with a magnetic stirrer. Seal the photoreaction tube, take it out of the glove box, and then irradiate it with a 6W purple 400nm LED lamp. The reaction mixture is stirred at room temperature for 12 hours. Then turn off the blue light and concentrate the reaction mixture under reduced pressure. The crude product is purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (30 / 1-10 / 1, v / v) to obtain the target compound G7 (colorless liquid 68.1 mg, yield 99%). 1HNMR (600MHz, CDCl3, 25℃) δ7.45–7.42(m,1H),7.35–7.32(m,1H),7.25–7.20(m,2H),7.12–7.09(m,2H),7.00(dd,J=6.6,1.8Hz,1H ),6.84–6.81(m,2H),6.76–6.72(m,1H),4.34(tdd,J=6.0,4.0,1.3Hz,1H),3.78(s,3H),3.63(dd,J=22.5,7.0Hz,1H),2.22(s,3H). 13 C NMR (151MHz, CDCl3, 25℃) δ205.7, 159.3, 143.5, 138.6 (d, J = 7.1Hz), 134.5, 132.4 (d, J = 5.7Hz), 126.9, 126.7, 126.6, 126.2 (d, J = 6 .2Hz), 125.13 (t, J=253.5Hz), 121.3, 114.1, 64.1 (d, J=4.3Hz), 57.4 (dd, J=26.2, 22.3Hz), 55.3, 50.7 (dd, J=27.2, 24.5Hz), 29.3. 19 FNMR (565MHz, CDCl3, 25℃) δ-84.5 (ddt, J=223.1, 22.4, 5.0Hz, 1F), -93.6 (dt, J=223.2, 5.7Hz, 1F).

[0070] Embodiment 11:

[0071]

[0072] In a glove box, A (62.4 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The blue light was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (30 / 1-10 / 1, v / v) to obtain the target compound G8 (colorless liquid 61.8 mg, yield 95%). 1HNMR (600MHz, CDCl3, 25℃) δ9.89(d,J=0.9Hz,1H),7.48(dd,J=7.2,1.2Hz,1H),7.37–7.32(m,1H),7.30–7.27(m,2H),7.05(dd,J=7.7,1. 5Hz,1H),6.76–6.72(m,1H),6.69(d,J=8.4Hz,2H),6.37(bs,2H),4.34(td,J=5.4,3.9Hz,1H),3.73(s,3H),3.52(dd,J=23.0,7.0Hz,1H). 13 C NMR (151MHz, CDCl3, 25℃) δ200.9 (d, J = 2.2Hz), 159.5, 138.7 (d, J = 6.6Hz), 138.3, 136.0, 132.3 (d, J = 6.5Hz), 131.5, 127.2, 126.9, 126.7, 124.6(dd,J=256.7,253.3Hz), 124.5(d,J=4.9Hz), 123.8,113.7,59.9(d,J=4.9Hz), 57.0(dd,J=26.8,22.0Hz), 55.3,50.3(t,J=25.8Hz). 19 F NMR (565MHz, CDCl3, 25℃) δ-84.6 (ddd, J=225.2, 22.6, 5.2Hz, 1F), -93.6–-94.1 (m, 1F).

[0073] Embodiment 12:

[0074]

[0075] In a glove box, A (74.4 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The blue light was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (30 / 1-10 / 1, v / v) to obtain the target compound G9 (colorless liquid 65.7 mg, yield 92%).

[0076] 11H NMR (600 MHz, CDCl3, 25 °C) δ 7.91 (dd, J = 6.9, 1.8 Hz, 1H, H’), 7.43–7.39 (m, 1H, H+H’), 7.33–7.23 (m, 2H, H+H’), 7.16–7.11 (m, 1H, H), 6.92–6.90 (m, 1H, H’), 6.83–6.81 (m, 1H, H’), 6.76–6.71 (m, 1H, H+H’), 6.64 (d, J = 8.3 Hz, 2H, H+H’), 6.31 (bs, 1H, H+H’), 4.37–4.33 (m, 1H, H’), 4.31–4.27 (m, 1H, H), 3.80–3.53 (m, 7H, H+H’). 13 13C NMR (151 MHz, CDCl3, 25 °C) δ 170.9 (C), 170.4 (C’), 159.2 (C’), 159.1 (C), 142.6 (C’), 139.2 (C), 138.3 (d, J = 6.8 Hz, C), 137.9 (d, J = 7.6 Hz, C’), 137.6 (C+C’), 135.0 (C+C’), 132.1 (C’), 132.0 (C+C’), 132.0 (C+C’), 131.4 (C+C’), 127.0 (C), 126.9 (C’), 126.9 (C), 126.8 (C’), 126.4 (C), 126.2 (C’), 126.0 (C), 125.8 (d, J = 4.7 Hz, C+C’), 121.8 (C’), 113.6 (C’), 113.1 (C), 59.6 (d, J = 5.1 Hz, C’), 58.5 (d, J = 5.2 Hz, C), 58.2 (dd, J = 26.9, 21.6 Hz, C+C’), 55.3 (C’), 55.1 (C), 52.3 (C’), 52.2 (C), 50.8 (t, J = 26.7 Hz, C’), 50.2 (t, J = 25.7 Hz, C). 19 19F NMR (565 MHz, CDCl3, 25 °C) δ -83.6 (ddd, J = 225.5, 23.9, 5.2 Hz, 1F, F), -84.9 (ddt, J = 223.9, 22.2, 4.7 Hz, 1F, F’), -93.3–-93.8 (m, 1F, F+F’).

[0077] Example 13:

[0078]

[0079] In a glove box, A (96 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The blue light was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (300 / 1-100 / 1, v / v) to obtain the target compound G10 (colorless liquid 80.3 mg, yield 96%).

[0080] 1 H NMR (600MHz, CDCl3, 25℃) δ8.11–8.09(m,1H),7.46–7.44(m,1H),7.39–7.31(m,4H),7.26–7.23(m,1H),7.12(dd,J=7.7,1.4Hz,1H),6.92–6. 88(m,2H),6.82(ddd,J=7.7,6.2,3.2Hz,1H),6.72–6.68(m,2H),6.47(bs,2H),4.38–4.34(m,1H),3.91(dd,J=23.4,7.3Hz,1H),3.74(s,3H). 13 C NMR (151MHz, CDCl3, 25℃) δ169.2,159.4,150.3,139.1,138.4(d,J=6.7Hz),137.2,132.3(d,J=6.5Hz),131.7,129.6,127.1,127.0,126.5,126.3, 126.1, 125.5 (d, J = 4.7Hz), 124.2 (dd, J = 255.4, 252.0Hz), 121.5, 113.3, 58.4 (dd, J = 27.3, 21.9Hz), 58.1 (d, J = 5.5Hz), 55.2, 50.2 (t, J = 25.8Hz). 19 F NMR (565MHz, CDCl3, 25℃) δ-83.8 (ddd, J=225.2, 23.3, 5.2Hz), -93.6 (dt, J=226.8, 6.7Hz).

[0081] Embodiment 14:

[0082]

[0083] In a glove box, A (61.2 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The blue light was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (30 / 1-10 / 1, v / v) to obtain the target compound G11 (colorless liquid 60.8 mg, yield 94%). 1 HNMR (600MHz, CDCl3, 25℃) δ7.66(dd,J=7.4,1.1Hz,1H,H'),7.48–7.43(m,1H,H+H'),7.42–7.31(m,3H,H+H' ),7.22(d,J=8.3Hz,2H,H'),6.93–6.91(m,2H,H'),6.89(dd,J=7.7,1.5Hz,1H,H),6.84–6.83(m,2H,H'),6. 78(ddd,J=7.6,6.3,3.2Hz,1H,H),6.72–6.69(m,2H,H),6.34(bs,2H,H),4.43–4.41(m,1H,H'),4.39–4.36( m,1H,H),3.82(s,3H,H'),3.74(s,3H,H),3.63(dd,J=22.5,6.8Hz,1H,H),3.36(dd,J=21.3,7.4Hz,1H,H'). 13C NMR (151MHz, CDCl3, 25℃) δ159.9(C'),159.8(C),139.0(C'),136.4(C),135.9(d,J=7.1Hz,C),135.8(d,J=7.5Hz,C'),135.1( C),133.5(d,J=6.1Hz,C'),133.3(C'),133.1(d,J=6.5Hz,C),131.5(C),131.0(C'),128.3(C),127.9(C'),127.8(C'),127.5( C),126.5(C'),126.4(C),124.7(C),123.9(d,J=4.1Hz,C+C'),123.0(dd,J=255.6,252.0Hz,C+C'),121.6(C'),117.9(C+C') ,114.1(C'),113.6,58.9(dd,J=28.1,22.8Hz,C'),58.1(dd,J=28.0,22.2Hz,C),55.3(C'),55.2(C),50.0–49.1(m,2C,C+C'). 19 F NMR (565MHz, CDCl3, 25℃) δ-83.7(ddd,J=228.0,22.6,5.2Hz,1F,F),-85.3–-85.9(m,1F,F'),-93.4–-94.3(m,1F,F+F').

[0084] Embodiment 15:

[0085]

[0086] In a glove box, A (115.2 mg, 0.6 mmol, 3 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The blue light was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (30 / 1-10 / 1, v / v) to obtain the target compound G12 (colorless liquid 56.9 mg, yield 62%).

[0087] 11H NMR (600 MHz, CDCl3, 25 °C) δ 7.93 (dd, J = 7.1, 1.7 Hz, 1H), 7.41 (dd, J = 6.9, 1.7 Hz, 1H), 7.37 (dd, J = 8.3, 6.9 Hz, 2H), 7.32–7.27 (pd, J = 7.5, 1.6 Hz, 3H), 7.21–7.18 (m, 2H), 6.93 (dd, J = 7.8, 1.4 Hz, 1H), 6.73 (ddd, J = 7.7, 6.2, 3.1 Hz, 1H), 6.67 (dd, J = 11.7, 1.8 Hz, 1H), 6.60 (d, J = 8.3 Hz, 2H), 6.32 (bs, 2H), 5.67 (dt, J = 11.7, 6.7 Hz, 1H), 4.88 (ddt, J = 9.6, 6.5, 3.2 Hz, 2H), 4.32–4.26 (m, 1H), 3.74–3.69 (m, 4H). 13 13C NMR (151 MHz, CDCl3, 25 °C) δ 170.3, 159.2, 139.3, 138.3 (d, J = 6.7 Hz), 137.7, 136.0, 133.5, 132.0 (d, J = 6.5 Hz), 131.5, 128.8, 128.6, 127.8, 127.0, 126.9, 126.4, 126.0, 125.8 (d, J = 4.8 Hz), 125.2, 124.4 (dd, J = 255.5, 252.0 Hz), 113.1, 62.3, 58.3, 58.2 (dd, J = 28.1, 22.2 Hz), 55.2, 50.2 (t, J = 25.8 Hz). 19 19F NMR (565 MHz, CDCl3, 25 °C) δ -83.7 (ddd, J = 225.7, 23.7, 5.2 Hz, 1F), -93.4 (dt, J = 226.1, 7.2 Hz, 1F).

[0088] Example 16:

[0089]

[0090] In a glove box, A (68.4 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a photoreaction tube that was dried and equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. The blue light was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (3 / 1-1 / 1, v / v) to obtain the target compound G13 (yellow solid 57.4 mg, yield 84%). 1 H NMR (600MHz, CDCl3, 25℃) δ7.44–7.27(m,3H,H+H'),7.25–7.14(m,2H,H+H'),6.8 6–6.82(m,1H,H'),6.77–6.66(m,3H,H+H'),5.89–5.82(m,1H,H+H'),5.66(s,1H, H'),5.22(s,1H,H),4.37–4.33(m,1H,H'),4.32–4.28(m,1H,H),3.78(s,3H,H'), 3.73(s,3H,H), 3.57(dd,J=23.2,6.3Hz,1H,H), 3.44(dd,J=22.4,6.8Hz,1H,H'). 13C NMR (151MHz, CDCl3, 25℃) δ170.8(C), 170.3(C'), 158.5(C), 158.1(C'), 142. 0(C'),138.5(C),138.2(C'),137.1(d,J=6.8Hz,C),136.7(d,J=7.4Hz,C'),1 33.8(C),131.3(d,J=5.7Hz,C'),130.1(d,J=6.6Hz,C),126.1(C),126.0(C' ),126.0(C),125.7(C'),125.3(C),125.2(C'),125.0(d,J=6.1Hz,C),124.9( d, J=6.0Hz, C'), 123.9 (dd, J=255.4, 252.2Hz, C'), 123.7 (dd, J=256.5, 252. 7Hz,C),123.7(C),120.7(C'),113.0(C),112.9(C'),58.1(d,J=5.2Hz,C),58 .0(d,J=4.4Hz,C'),56.7(dd,J=26.2,22.3Hz,C'),55.8(dd,J=26.1,21.9Hz, C),54.1(C'),54.1(C),49.4(dd,J=26.7,24.8Hz,C'),48.8(t,J=25.8Hz,C). 19 F NMR (565MHz, CDCl3, 25℃) δ-84.4--85.0(m,1F,F+F'),-90.5--90.9(m,1F,F),-93.2(dt,J=223.3,5.6Hz,1F,F').

[0091] Embodiment 17:

[0092]

[0093] In a glove box, A (68.8 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol) and fac-(dFppy)3 (3 mg, 2 mol%), and dry DCM (2 mL) were added to a dry photoreaction tube equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6 W purple 400 nm LED lamp. The reaction mixture was stirred at room temperature for 12 hours. Then the blue light was turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE / EA (2 / 1-1 / 1, v / v) to obtain the target compound G14 (colorless liquid 62.4 mg, yield 91%).

[0094] 1 H NMR(600MHz,CDCl3,25℃)δ7.98(dd,J=6.9,1.8Hz,1H,H),7.43–7.38(m,1H,H+H’),7.32–7.15(m,3H,H+H’),6.96–6.92(m,1H,H+H’),6.81(d,J=8.4Hz,2H,H’),6.76–6.69(m,1H,H+H’),6.61(d,J=8.4Hz,2H,H),6.37–6.31(bs,1H,H+H’),4.35–4.32(m,1H,H’),4.29–4.26(m,1H,H),3.77(d,J=0.7Hz,3H,H’),3.75–3.71(m,1H,H),3.70(d,J=0.7Hz,3H,H),3.55(dd,J=22.5,7.4Hz,1H,H’). 13 C NMR(151MHz,CDCl3,25℃)δ174.0(C),173.0(C’),159.0(C’),159.0(C),142.3(C’),139.2(C),138.3(d,J=6.6Hz,C),137.8(d,J=7.3Hz,C’),137.5(C’),135.0(C),131.9(d,J=6.6Hz,C),126.9(C’),126.8(C),126.7(C),126.6(C’),126.4(C),126.0(C’),125.8(C),125.7(d,J=4.6Hz,C),124.8(dd,J=255.7,252.1Hz,C’),124.3(dd,J=256.8,252.5Hz,C),121.9(C’),113.5(C’),112.9(C),58.2–57.7(m,C+C’),55.2(C’),55.1(C),50.8–50.4(t,J=25.6Hz,C’),50.1(t,J=25.7Hz,C),39.5–38.9(m,C+C’). 19 FNMR(565MHz,CDCl3,25℃)δ-83.6(ddd,J=225.6,23.9,5.4Hz,1F,F),-85.0(ddt,J=224.0,22.4,4.6Hz,1F,F’),-93.1–-93.7(m,1F,F+F’).

[0095] The above is only a preferred embodiment of the present invention, which certainly cannot be used to limit the scope of rights of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and changes can be made without departing from the principle of the present invention, and these improvements and changes are also regarded as the protection scope of the present invention.

Claims

1. A benzodifluorocyclohexane bridged ring compound, characterized in that: Its molecular structure is shown in G: Among them, R1, R2, R3, R4, and R5 are each a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, an ester group, an aldehyde group, a cyano group, or a halogen group, but they are not all hydrogen atoms at the same time, and they may be the same or different.

2. The benzodifluorocyclohexane bridged ring compound according to claim 1, characterized in that: The alkyl group has 1 to 20 carbon atoms and is a straight chain structure, a cyclic structure or a branched structure; the alkyl group carries one or more substituents. When there are multiple substituents, the substituents may be the same or different, and the positions may be the same or different.

3. The benzodifluorocyclohexane bridged ring compound according to claim 1, characterized in that: The aryl group has one or more substituents; when having multiple substituents, the substituents may be the same or different.

4. A method for preparing a benzodifluorocyclohexane bridged ring compound as claimed in any one of claims 1 to 3, characterized in that: The benzodifluorocyclohexane bridged ring compound G can be obtained by mixing naphthalene A, difluoroolefin B, a catalyst and an organic solvent, stirring and reacting under light at a temperature of -78°C to 180°C, and then separating and purifying.

5. The method for preparing the benzodifluorocyclohexane bridged ring compound according to claim 4, characterized in that: The molecular structural formula of the naphthalene A is: The molecular structural formula of the difluoroolefin B is:

6. The method for preparing the benzodifluorocyclohexane bridged ring compound according to claim 4, characterized in that: The catalyst is any one of an Ir-based photocatalyst, a Ru-based photocatalyst, a carbazole-based photocatalyst, an acridine-based photocatalyst, and Solvent Red 43.

7. The method for preparing the benzodifluorocyclohexane bridged ring compound according to claim 4, characterized in that: The organic solvent is methanol, ethanol, isopropanol, tert-butyl alcohol, tetrahydrofuran, 2-methyltetrahydrofuran, ether, dimethyl ethyl diether, methyl tert-butyl ether, 1,4-epoxyhexadecane, 1,3-epoxyhexadecane, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, C 4-12 Saturated alkanes, C 3-12 Fluorinated or chlorinated alkanes, benzene, toluene, xylene, trimethylbenzene, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, acetone, N-methylpyrrolidone, acetonitrile, C 3-12 At least one of the saturated alkyl nitriles.

8. The method for preparing the benzodifluorocyclohexane bridged ring compound according to claim 4, characterized in that: The molar ratio of naphthalene A to difluoroolefin B is 1-2:1; the amount of the catalyst is 0.15% to 5% of the molar amount of difluoroolefin B, and the concentration of difluoroolefin B in the mixed solution is between 0.1M and 1M.

9. Use of the benzodifluorocyclohexane bridged ring compound according to any one of claims 1 to 3 or the benzodifluorocyclohexane bridged ring compound prepared by the preparation method according to any one of claims 4 to 8 as an organic intermediate in drug synthesis or post-modification of complex molecules and drug molecules.

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