Difluorocyclobutane fused ring compound and preparation method and application thereof

Abstract

The invention relates to the technical field of organic synthesis, in particular to a difluorocyclobutane ring-fused compound as well as a preparation method and application thereof, the molecular structural formula of the difluorocyclobutane ring-fused compound is shown as G: # imgabs0 #, and R1, R2, R3 and R4 are 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 difluorocyclobutane fused ring compound provided by the invention is an important organic intermediate, can be used for synthesis of various drugs, and can also be used for later modification of complex bioactive molecules and drug molecules. The preparation method provided by the invention realizes 2 + 2 cyclization reaction of intracyclic olefin A and difluoroolefin B. A simple and efficient method is provided for synthesizing the difluorocyclobutane ring-fused compound, and the method can be applied to synthesizing various substituted difluorocyclobutane ring-fused compounds and has good substrate universality and functional group tolerance.

Description

Technical Field

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

[0002] Cyclobutane is a common structural unit in bioactive molecules. [a) S.-L. You, Angew. Chem. Int. Ed. 2021, 60, 7036–7040; b) R. Gilmour, Org. Lett. 2019, 21, 9724–9727] Fluorine atoms have a small atomic radius but high electronegativity. Fluorine atoms also enhance the lipophilicity of the molecule, making it easier for the drug molecule to enter cells. Fluorine atoms can also enhance the biochemical stability of drug molecules and improve drug utilization. Therefore, fluorine-containing groups are gaining increasing attention in medicinal chemistry. Currently, one-third of small molecule drugs on the market contain fluorine atoms. [a) W.K. Hagmann, J. Med. Chem., 2008, 51, 4359; b) F. Diederich, Science, 2007, 217, 1771] Therefore, difluorocyclobutane cyclodextrins have potentially important applications in drug molecules. However, due to the lack of synthetic methods, there are very few reports of this type of molecule in the literature. The few examples of fluorinated cyclobutyl ethers are all synthesized from difluorocyclobutanes under the promotion of high-energy ultraviolet light [a) B. Thorsten, Heterocycles 2014, 88, 1079-1100; b) B. Thorsten, Chem. Commun. 2013, 49, 2979-2991].

[0003] Since difluorocyclobutane cyclopentane compounds are difficult to obtain, there are few reports on their synthetic applications. Summary of the Invention

[0004] One of the purposes of the present invention is to provide a difluorocyclobutane cyclic 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 difluorocyclobutane cyclic 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 difluorocyclobutane cyclic compound.

[0007] The solution adopted by the present invention to achieve one of the objectives is: a difluorocyclobutane cyclic compound, whose molecular structure is shown in G:

[0008]

[0009] Wherein, R1, R2, R3, and R4 are any one of a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, an ester group, an aldehyde group, a cyano group, and 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 it has multiple substituents, the substituents may be the same or different.

[0012] The solution adopted by the present invention to achieve the second purpose is: a method for preparing the difluorocyclobutane cyclic compound: mixing an intracyclic olefin A and a difluoroolefin B, a catalyst, and an organic solvent, stirring the mixture under light and at a temperature of -77°C to 170°C, and then separating and purifying the mixture to obtain a difluorocyclobutane cyclic compound G.

[0013] Preferably, the molecular structural formula of the endocyclic olefin A is:

[0014] The molecular structural formula of the difluoroolefin B is:

[0015] 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.

[0016] Preferably, the catalyst is tris[2-phenylpyridine-C2,N]iridium(III), bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium bis(hexafluorophosphate), bis[2-(2,4-difluorophenyl)-5-methylpyridine][2,2'-bi(tetra-tert-butylpyridine)]iridium bis(hexafluorophosphate), bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bipyridine]iridium bis(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'-bipyridyl)bis[2-(4-fluorophenyl)pyridyl]iridium(III) hexafluorophosphate, (2,2'-bipyridyl)bis[2-(2,4-difluorophenyl)pyridyl]iridium(III) hexafluorophosphate, (2,2'-bipyridyl)bis[2-(4-tert-butylphenyl)pyridyl]iridium(III) hexafluorophosphate, (2-2'-bipyridyl)bis[2-(4-tert-butylphenyl)pyridyl]iridium(III) hexafluorophosphate -tert-butylpyridine)bis[2-(4-tert-butylphenyl)pyridine]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 [Iridium] tris(1,10-phenanthroline)ruthenium(II) bis(hexafluorophosphate), tris(4,4'-dimethyl-2,2'-bipyridyl)ruthenium(III) (hexafluorophosphate), tris(2,2'-bipyridyl)ruthenium bis(hexafluorophosphonate), tris(2,2'-bipyridyl)ruthenium bis(hexafluorophosphate), tris(2,2'-bipyridyl)ruthenium di(perchlorate), tris(2,2'-bipyridyl)ruthenium bis(tetrafluoroborate), tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate, 9-mesityl-10-phenylacridine-10-tetrafluoroborate, 2,3,5,6-tetrakis(9-carbazolyl)-terephthalonitrile, 2,4,5,Any one of 6-tetrakis(9-carbazolyl)isophthalonitrile (4CzIPN), a derivative of 4CzIPN, tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate, and Solvent Red 43.

[0017] Preferably, the organic solvent is methanol, ethanol, isopropanol, tert-butanol, 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.

[0018] Preferably, the molar ratio of the endocyclic olefin A to the difluoroolefin B is 1-2:1; the amount of the catalyst is 0.15% to 5% of the molar amount of the difluoroolefin B, and the concentration of the difluoroolefin B in the mixed solution is between 0.1M and 1M.

[0019] The illumination process can be performed using any one of white light, blue light, purple light, green light, sunlight, or other illumination methods. After the reaction is completed, the present invention performs post-treatment on the reaction product, including purification methods such as filtration, concentration, recrystallization, and column chromatography, which are all conventional methods in the art.

[0020] The solution adopted by the present invention to achieve the third purpose is: the difluorocyclobutane cyclopentane compound is used as an organic intermediate in drug synthesis or in the later modification of complex molecules and drug molecules.

[0021] The method of the present invention achieves the first synthesis of difluorocyclobutane paracyclic compounds by reacting a simple endocyclic olefin A and a difluoroolefin B under light. This single-step synthesis of difluorocyclobutane paracyclic compounds is applicable to the synthesis of various substituted difluorocyclobutane paracyclic compounds, exhibiting good substrate universality and functional group tolerance. The synthesized difluorocyclobutane paracyclic compounds are important organic intermediates that can be used in the synthesis of various drugs and have broad application prospects. Furthermore, the method can also be used for post-modification of complex molecules and drug molecules.

[0022] The present invention has the following advantages and beneficial effects:

[0023] (1) The difluorocyclobutane cyclopentane compounds of the present invention are novel compounds and important organic intermediates that can be used in the synthesis of various drugs and have broad application prospects. In addition, they can also be used for post-modification of complex bioactive molecules and drug molecules.

[0024] (2) The preparation method of the present invention realizes the 2+2 cyclization reaction of the endocyclic olefin A and the difluoroolefin B. It provides a simple and efficient method for synthesizing difluorocyclobutane cyclocyclic compounds. The method can be applied to the synthesis of various substituted difluorocyclobutane cyclocyclic compounds. It has good substrate universality and functional group tolerance and is compatible with various functional groups such as ester groups, halogens, and carbonyl groups. Various linear or branched alkyl groups can also complete the reaction.

[0025] (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

[0026] 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.

[0027] Example 1:

[0028]

[0029] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (1 mL). The photoreactor tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 (74.6 mg, 99% yield, white solid). 1 H NMR (600MHz, CDCl3, 25℃) δ7.00 (d, J=7.9Hz, 1H), 7.95–7.91 (m, 1H), 7.40–7.32 (m, 5H), 7.31–7.26 (m, 3H), 7 .19–7.15(m,1H),7.11(dd,J=7.5,1.5Hz,1H),4.31(dd,J=15.6,7.7Hz,1H),3.97–3.77(m,2H),1.32(s,9H). 13C NMR (151MHz, CDCl3, 25℃) δ150.7,133.6(d,J=3.7Hz),132.1,131.9,130.9,130.7,129.1,127.3,127.3,127.1,127.1,127.9,127.7(d,J=5 .2Hz),125.6,124.0,123.6,121.4(dd,J=302.3,275.3Hz),59.3(t,J=21.3Hz),47.1(dd,J=25.0,19.9Hz),34.7,34.4(d,J=16.0Hz),31.5. 19 F NMR (565MHz, CDCl3, 25℃) δ-91.0 (dd, J=174.5, 9.7Hz, 1F), -107.9–-107.9 (m, 1F).

[0030] Example 2:

[0031]

[0032] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol), fac-(dFppy)3 (3 mg, 2 mol%), and dry toluene (1 mL). The photoreactor tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 (67.4 mg, 90% yield, white solid). 1 H NMR (600MHz, CDCl3, 25℃) δ7.00 (d, J=7.9Hz, 1H), 7.95–7.91 (m, 1H), 7.40–7.32 (m, 5H), 7.31–7.26 (m, 3H), 7 .19–7.15(m,1H),7.11(dd,J=7.5,1.5Hz,1H),4.31(dd,J=15.6,7.7Hz,1H),3.97–3.77(m,2H),1.32(s,9H). 13C NMR (151MHz, CDCl3, 25℃) δ150.7,133.6(d,J=3.7Hz),132.1,131.9,130.9,130.7,129.1,127.3,127.3,127.1,127.1,127.9,127.7(d,J=5 .2Hz),125.6,124.0,123.6,121.4(dd,J=302.3,275.3Hz),59.3(t,J=21.3Hz),47.1(dd,J=25.0,19.9Hz),34.7,34.4(d,J=16.0Hz),31.5. 19 F NMR (565MHz, CDCl3, 25℃) δ-91.0 (dd, J=174.5, 9.7Hz, 1F), -107.9–-107.9 (m, 1F).

[0033] Example 3:

[0034]

[0035] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol), and 4-CzIPN (4 mg, 2 mol%) in dry DCM (1 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 (64.3 mg, 76% yield, white solid). 1 H NMR (600MHz, CDCl3, 25℃) δ7.00 (d, J=7.9Hz, 1H), 7.95–7.91 (m, 1H), 7.40–7.32 (m, 5H), 7.31–7.26 (m, 3H), 7 .19–7.15(m,1H),7.11(dd,J=7.5,1.5Hz,1H),4.31(dd,J=15.6,7.7Hz,1H),3.97–3.77(m,2H),1.32(s,9H). 13C NMR (151MHz, CDCl3, 25℃) δ150.7,133.6(d,J=3.7Hz),132.1,131.9,130.9,130.7,129.1,127.3,127.3,127.1,127.1,127.9,127.7(d,J=5 .2Hz),125.6,124.0,123.6,121.4(dd,J=302.3,275.3Hz),59.3(t,J=21.3Hz),47.1(dd,J=25.0,19.9Hz),34.7,34.4(d,J=16.0Hz),31.5. 19 F NMR (565MHz, CDCl3, 25℃) δ-91.0 (dd, J=174.5, 9.7Hz, 1F), -107.9–-107.9 (m, 1F).

[0036] Example 4:

[0037]

[0038] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (1 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 (56.1 mg white solid, 75% yield). 1 H NMR (600MHz, CDCl3, 25℃) δ7.00 (d, J=7.9Hz, 1H), 7.95–7.91 (m, 1H), 7.40–7.32 (m, 5H), 7.31–7.26 (m, 3H), 7 .19–7.15(m,1H),7.11(dd,J=7.5,1.5Hz,1H),4.31(dd,J=15.6,7.7Hz,1H),3.97–3.77(m,2H),1.32(s,9H). 13C NMR (151MHz, CDCl3, 25℃) δ150.7,133.6(d,J=3.7Hz),132.1,131.9,130.9,130.7,129.1,127.3,127.3,127.1,127.1,127.9,127.7(d,J=5 .2Hz),125.6,124.0,123.6,121.4(dd,J=302.3,275.3Hz),59.3(t,J=21.3Hz),47.1(dd,J=25.0,19.9Hz),34.7,34.4(d,J=16.0Hz),31.5. 19 F NMR (565MHz, CDCl3, 25℃) δ-91.0 (dd, J=174.5, 9.7Hz, 1F), -107.9–-107.9 (m, 1F).

[0039] Example 5:

[0040]

[0041] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (31.6 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (1 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G2 (59.9 mg, 79% yield, white solid). 1 H NMR (600MHz, CDCl3, 25℃) δ7.03(d,J=7.9Hz,1H),7.96(dd,J=7.1,1.2Hz,1H),7.44–7.40(m,1H),7.39–7.36(m,2H),7.35–7.31(m, 3H),7.22–7.19(m,1H),7.10–7.05(m,3H),4.33(dd,J=15.7,9.2Hz,1H),3.94(dt,J=17.0,9.9Hz,1H),3.76(td,J=9.6,1.9Hz,1H). 13CNMR (151MHz, CDCl3, 25℃) δ162.5 (d, J = 246.5Hz), 133.2 (d, J = 3.7Hz), 132.0, 13 1.9,130.9,130.1(d,J=7.2Hz),129.6(d,J=3.3Hz),127.9,127.4,127.3,127.2, 127.1,127.5(d,J=5.0Hz),124.1,123.6,121.2(dd,J=302.7,274.7Hz),115.6(d ,J=21.5Hz), 57.7(t,J=21.4Hz), 47.1(dd,J=24.9,19.9Hz), 35.0(d,J=16.3Hz). 19 F NMR (565MHz, CDCl3, 25℃) δ-91.0 (dd, J=174.9, 9.7Hz, 1F), -109.4 (dt, J=174.9, 16.9Hz, 1F), -114.46–-114.55 (m, 1F).

[0042] Example 6:

[0043]

[0044] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (34.7 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (1 mL). The photoreactor tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G3 (67.9 mg, 96% yield, white solid). 1 H NMR (600MHz, CDCl3, 25℃) δ7.02(d,J=7.9Hz,1H),7.95(dd,J=7.1,1.2Hz,1H),7.43–7.40(m,1H),7.37–7.32(m,5H),7.30–7.27(m,2H), 7.22–7.17(m,1H),7.07(dd,J=7.6,1.4Hz,1H),4.33(dd,J=15.7,9.2Hz,1H),3.93(dt,J=17.7,9.7Hz,1H),3.76(td,J=9.5,1.9Hz,1H). 13C NMR (151MHz, CDCl3, 25℃) δ133.7,133.1(d,J=3.7Hz),132.3,132.0,131.9,131.0,129.9,127.9,127.5,127.4,127.2,127.2,1 27.4, 127.4, 124.1, 123.6, 121.1 (dd, J = 302.7, 274.9Hz), 57.9 (t, J = 21.3Hz), 47.1 (dd, J = 25.0, 20.0Hz), 34.7 (d, J = 16.0Hz). 19 F NMR (565MHz, CDCl3, 25℃) δ-90.9 (dd, J=175.7, 9.9Hz, 1F), -109.2 (dt, J=175.6, 16.9Hz 1F).

[0045] Example 7:

[0046]

[0047] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (43.4 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (1 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G4 (77.7 mg, 97% yield, white solid). 1 H NMR (400MHz, CDCl3, 25℃) δ7.04–7.00(m,1H),7.95(dd,J=7.0,1.2Hz,1H),7.53–7.47(m,2H),7.44–7.37(m,1H),7 .37–7.31(m,3H),7.26–7.17(m,3H),7.07(dd,J=7.5,1.4Hz,1H),4.33(dd,J=15.7,7.7Hz,1H),3.97–3.71(m,2H). 13C NMR (151MHz, CDCl3, 25℃) δ133.1(d,J=3.6Hz),132.7,132.0,131.9,131.7,131.0,130.2,127.9,127.5,127.3,127.2,127.1,127.3( d, J=5.0Hz), 124.1, 123.6, 121.9, 121.0 (dd, J=302.7, 274.9Hz), 57.7 (t, J=21.3Hz), 47.1 (dd, J=24.7, 20.0Hz), 34.7 (d, J=15.9Hz). 19 F NMR (376MHz, CDCl3, 25℃) δ-90.7 (dd, J=174.9, 9.4Hz, 1F), -107.7–-109.5 (m, 1F). HRMS (ESI, m / z):calcd for C 22 H 16 BrF2 + (M+H) + :397.0397; found:397.0377.

[0048] Example 7:

[0049]

[0050] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (53.0 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (1 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 (77.9 mg, 99% yield, white solid). 1 H NMR (600MHz, CDCl3, 25℃) δ7.03–7.01(m,1H),7.95(dd,J=7.0,1.2Hz,1H),7.72–7.69(m,2H),7.43–7.40(m,1H),7.37–7.32 (m,3H),7.21–7.17(m,1H),7.12–7.09(m,2H),7.07(dd,J=7.5,1.4Hz,1H),4.33(dd,J=15.7,9.0Hz,1H),3.94–3.73(m,2H).13 C NMR (151MHz, CDCl3, 25℃) δ137.7,133.5,133.1(d,J=3.7Hz),132.0,131.9,131.0,130.4,127.9,127.5,127.4,127.2,127.2,127.4( d, J=5.0Hz), 124.1, 123.6, 121.0 (dd, J=302.9, 274.7Hz), 93.6, 59.0 (t, J=21.0Hz), 47.1 (dd, J=24.9, 20.0Hz), 34.6 (d, J=16.2Hz). 19 F NMR (565MHz, CDCl3, 25℃) δ-90.7 (dd, J=175.5, 9.6Hz, 1F), -109.1 (dt, J=175.2, 17.1Hz, 1F). HRMS (ESI, m / z): calcd for C 22 H 16 IF2 + (M+H) + :445.0259; found:445.0254.

[0051] Example 9:

[0052]

[0053] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (1 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G6 (69.4 mg, 97% yield, white solid). 11H NMR (600 MHz, CDCl3, 25 °C) δ 7.03 (d, J = 7.9 Hz, 1H), 7.95 (dd, J = 7.1, 1.2 Hz, 1H), 7.43–7.39 (m, 1H), 7.36 (d, J = 4.4 Hz, 2H), 7.34–7.31 (m, 1H), 7.31–7.27 (m, 2H), 7.20–7.17 (m, 1H), 7.07 (dd, J = 7.6, 1.4 Hz, 1H), 6.94–6.91 (m, 2H), 4.32 (dd, J = 15.7, 7.9 Hz, 1H), 3.95–3.74 (m, 2H), 3.72 (s, 3H). 13 13C NMR (151 MHz, CDCl3, 25 °C) δ 159.2, 133.4 (d, J = 3.7 Hz), 131.9, 131.7, 130.7, 129.6, 127.7, 127.2, 127.2, 127.0, 127.9, 127.6 (d, J = 5.1 Hz), 125.7, 123.9, 123.5, 121.4 (dd, J = 302.7, 274.9 Hz), 114.0, 57.9 (t, J = 21.3 Hz), 55.3, 46.9 (dd, J = 24.9, 20.0 Hz), 34.7 (d, J = 16.4 Hz). 19 19F NMR (565 MHz, CDCl3, 25 °C) δ -91.3 (dd, J = 174.6, 9.9 Hz, 1F), -109.1 (dt, J = 174.2, 16.6 Hz, 1F). HRMS (APCI, m / z): calcd for C 23 H 19 F2O + (M + H) + : 349.1399; found: 349.1392.

[0054] Example 10:

[0055]

[0056] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (33 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (1 mL). The photoreactor tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G7 (62.5 mg, 91% yield, white solid). 1 HNMR (600MHz, CDCl3, 25℃) δ7.05–7.01(m,1H),7.97–7.94(m,1H),7.69–7.64(m,2H),7.47(d,J=7.1Hz,2H),7.45–7.41(m,1H),7.40–7.33(m, 3H),7.25–7.20(m,1H),7.07(dd,J=7.5,1.4Hz,1H),4.36(dd,J=15.7,9.3Hz,1H),4.01(dt,J=17.4,9.7Hz,1H),3.90(td,J=9.6,1.7Hz,1H). 13 C NMR (151MHz, CDCl3, 25℃) δ139.3, 132.6 (d, J = 3.7Hz), 132.5, 131.9, 131.0, 129.2, 127.9, 127.6, 127.5, 127.4, 127.3, 127.0 (d, J = 5. 0Hz), 124.3, 123.7, 120.7 (dd, J = 303.2, 274.6Hz), 117.7, 111.7, 57.9 (t, J = 21.3Hz), 47.3 (dd, J = 24.7, 19.9Hz), 34.7 (d, J = 15.7Hz). 19 F NMR (565MHz, CDCl3, 25℃) δ-90.1 (dd, J=176.0, 9.7Hz, 1F), -109.1 (dt, J=175.9, 17.0Hz, 1F). HRMS (ESI, m / z): calcd for C 23 H 16 F2N + (M+H) + :344.1245; found:344.1234.

[0057] Example 11:

[0058]

[0059] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (37.7 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (2 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G8 as a white solid (73.0 mg, 97% yield). 1 H NMR (400MHz, CDCl3, 25℃) δ7.02(d,J=7.7Hz,1H),7.95(dd,J=7.1,1.2Hz,1H),7.43–7.37(m,1H),7.37–7.33(m,2H),7.33–7.27(m,3H),7.21–7.15(m ,1H),7.07(dd,J=7.5,1.5Hz,1H),7.02–6.97(m,2H),4.70(d,J=2.4Hz,2H ),4.32(dd,J=15.7,7.6Hz,1H),3.97–3.72(m,2H),2.54(t,J=2.3Hz,1H). 13 C NMR (151MHz, CDCl3, 25℃) δ 157.3, 133.5 (d, J = 3.7Hz), 132.0, 131.9, 130.9, 129.7, 127.9, 127.3, 127.3, 127.1, 127.0, 127.7 (d, J = 5.0Hz), 126 .7,124.0,123.6,121.4(dd,J=302.6,274.7Hz),115.0,77.7,75.7,57.9(t,J=21.3Hz),55.9,47.0(dd,J=24.9,20.0Hz),34.7(d,J=16.3Hz). 19 F NMR (376MHz, CDCl3, 25℃) δ-91.1 (dd, J=174.7, 9.1Hz, 1F), -107.6–-109.5 (m, 1F). HRMS (ESI, m / z):calcd forC 25 H 19 F2O + (M+H) +:373.1399; found:373.1377.

[0060] Example 12:

[0061]

[0062] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (44.7 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (2 mL). The photoreactor tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G9 (69.0 mg, 76% yield, white solid). 1 H NMR (400MHz, CDCl3, 25℃) δ7.02(d,J=7.7Hz,1H),7.94(dd,J=7.1,1.2Hz,1H),7.43–7.37(m, 1H),7.37–7.34(m,2H),7.34–7.29(m,1H),7.29–7.25(m,2H),7.20–7.16(m,1H),7.07(dd,J =7.5,1.5Hz,1H),6.94–6.90(m,2H),5.51(ddq,J=6.7,5.4,1.4Hz,1H),4.55–4.47(m,2H),4 .32(dd,J=15.7,7.5Hz,1H),3.96–3.72(m,2H),1.71(d,J=1.2Hz,3H),1.75(d,J=1.3Hz,3H). 13 C NMR (151MHz, CDCl3, 25℃) δ157.6, 137.5, 133.6 (d, J = 3.6Hz), 132.1, 131.9 ,130.9,129.7,127.9,127.3,127.3,127.1,127.9,127.7(d,J=5.0Hz),125 .7,124.0,123.6,121.5(dd,J=302.6,274.7Hz),119.7,114.7,64.9,59.0 (t, J=21.3Hz), 47.0 (dd, J=25.1, 20.1Hz), 34.7 (d, J=16.4Hz), 26.0, 17.3. 19F NMR (376MHz, CDCl3, 25℃) δ-90.9–-91.4(m,1F),-107.6–-109.3(m,1F).

[0063] Example 13:

[0064]

[0065] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (42 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (2 mL). The photoreactor tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 (63.1 mg, 71% yield, white solid). 1 HNMR (600MHz, CDCl3, 25℃) δ7.97 (dd, J=7.9, 1.2Hz, 2H), 7.47–7.43 (m, 4H), 7.41–7.37 (m, 2H ),7.36–7.33(m,2H),7.32–7.29(m,2H),4.35–4.30(m,2H),1.37(s,9H),1.11–1.09(m,3H). 13 C NMR (151MHz, CDCl3, 25℃) δ149.7, 139.7 (d, J = 2.6Hz), 132.9, 132.2, 131.2, 131. 0(d,J=3.3Hz),130.6,127.6(d,J=5.0Hz),127.2,127.1,127.0,127.9,126.1,12 5.4,123.7,123.3,122.1(dd,J=304.2,279.2Hz),60.6(dd,J=22.6,20.2Hz),46. 0(dd,J=26.4,20.9Hz),36.4(dd,J=13.0,2.5Hz),34.6,31.5,21.5(d,J=5.7Hz). 19 F NMR (565MHz, CDCl3, 25℃) δ-94.0 (ddt, J=176.7, 17.1, 4.9Hz, 1F), -102.9 (d, J=176.1Hz, 1F).

[0066] Example 14:

[0067]

[0068] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (37.6 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (2 mL). The photoreactor tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G11 (67.1 mg white solid, 93% yield). 1 H NMR (600MHz, CDCl3, 25℃) δ7.01–7.97(m,2H),7.43(d,J=7.6Hz,2H),7.42–7.32(m,7H),7.32–7.29(m,1H),4.35–4.25(m,2H),1.10–1.07(m,3H). 13 C NMR (151MHz, CDCl3, 25℃) δ141.2 (d, J = 2.7Hz), 132.9, 132.7, 132.0, 131.1, 1 30.3(d,J=3.5Hz),130.3,127.6,127.2,127.2(d,J=5.1Hz),127.1,127.0,12 7.7,123.7,123.3,121.6(dd,J=304.6,277.5Hz),60.36(dd,J=22.9,20.1Hz) ,45.90(dd,J=26.2,20.7Hz), 36.53(dd,J=13.1,2.1Hz), 21.34(d,J=5.5Hz). 19 F NMR (565MHz, CDCl3, 25℃) δ-94.4 (dd, J=176.7, 17.2Hz, 1F), -102.6 (d, J=176.7Hz, 1F). HRMS (APCI, m / z): calcd for C 23 H 17 ClF2 + (M+H) + :367.1060; found:367.1047.

[0069] Example 15:

[0070]

[0071] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (45 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (2 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G12 as a white solid (79.0 mg, 97% yield). 1 HNMR (600MHz, CDCl3, 25℃) δ7.01–7.91(m,2H,H+H'),7.40–7.37(m,1H,H+H'),7.33(d,J=4.6Hz,2H,H+H'),7.31–7 .26(m,1H,H+H'),7.26–7.21(m,2H,H+H'),7.17–7.13(m,1H,H),7.05(dd,J=7.6,1.4Hz,1H,H),6.95–6.91(m,1H,H '),6.90–6.77(m,2H,H+H'),6.73–6.64(m,1H,H),6.36–6.34(m,1H,H'),4.51–4.42(m,1H,H'),4.36–4.26(m,1H,H +H'),4.11(ddd,J=11.0,9.1,6.4Hz,1H,H'),3.91–3.77(m,6H,H+H'),3.17–3.13(m,4H,H),3.11–3.06(m,4H,H'). 1313C NMR (151 MHz, CDCl3, 25 °C) δ 150.9 (C), 150.7 (C’), 133.6 (d, J = 3.5 Hz), 133.3 (C’), 132.5 (C’), 132.3 (C), 132.0 (C), 131.9 (C), 131.7 (C’), 130.9 (C), 130.5 (C’), 130.0 (C’), 129.4 (C), 127.9 (C), 127.6 (C’), 127.3 (C + C’), 127.2 (C + C’), 127.1 (C + C’), 127.9 (C + C’), 127.7 (d, J = 4.7 Hz, C’), 127.3 (d, J = 3.7 Hz, C), 124.9 (C), 123.9 (C), 123.6 (C), 123.5 (C’), 123.3 (C’), 123.1 (C’), 121.6 (dd, J = 302.7, 274.9 Hz, C + C’), 115.6 (C), 114.6 (C’), 67.0 (C), 67.0 (C’), 59.1 (t, J = 21.3 Hz, C), 57.2 (dd, J = 21.4, 21.1 Hz, C’), 49.2 (C), 49.1 (C’), 第47.4 (t, J = 22.2 Hz, C’), 46.9 (dd, J = 24.9, 20.0 Hz, C), 34.7 (d, J = 16.4 Hz, C), 33.7 (d, J = 20.7 Hz, C’). 19 19F NMR (565 MHz, CDCl3, 25 °C) δ -77.9– -77.4 (m, 1F, F’), -91.3 (dt, J = 173.6, 7.6 Hz, 1F, F), -107.5– -109.1 (m, 1F, F), -117.0 (dt, J = 177.7, 16.7 Hz, 1F, F’). HRMS (ESI, m / z): calcd for C 26 H 24 F2NO + (M + H) + : 404.1721; found: 404.1711.

[0072] Example 16:

[0073]

[0074] It should be noted that there seems to be an error in the Chinese description of the "第47.4" in the 13C NMR part, which is translated as "第47.4" here. It might need to be corrected in the original Chinese text for a more accurate translation context.In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (71.2 mg, 0.4 mmol, 2 equiv.), B (34 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (2 mL). The photoreactor tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G13 as a white solid (71.6 mg, 96% yield). 1 HNMR(600MHz, 600MHz, CDCl3, 25℃) δ7.06–7.97(m,2H,H+H'),7.50–7.37(m,4H,H+H'),7.36–7.29 (m,2H,H+H'),7.04–7.01(m,1H,H),6.99–6.96(m,1H,H+H'),6.74(d,J=7.6Hz,1H,H+H'),6.76–6 .74(m,1H,H+H'),6.49(dd,J=7.7,1.3Hz,1H,H'),4.79–4.73(m,1H,H),4.73(dd,J=15.5,3.6Hz, 1H,H),4.69–4.64(m,1H,H'),4.14(dd,J=16.3,12.0Hz,1H,H'),3.74(s,3H,H),3.79(s,3H,H'). 1313C NMR (151 MHz, CDCl3, 25 °C) δ 160.3 (C), 160.3 (C’), 132.6 (C), 132.3 (C), 132.3 (C’), 132.2 (C), 132.1 (C’), 130.9 (C’), 130.7 (C), 130.7 (C’), 130.3 (C), 129.7 (C), 129.7 (C), 129.6 (C), 129.6 (C’), 129.6 (C’), 129.3 (C), 129.3 (C’), 127.9 (C’), 127.1 (C), 127.0, 124.7 (C), 124.4 (d, J = 3.1 Hz, C), 124.3 (C), 124.1 (C’), 123.7 (C), 123.7 (C’), 122.5 (C), 122.2–122.1 (m, C), 121.2 (C’), 120.67 (dd, J = 293.0, 270.5 Hz, C), 120.3 (d, J = 2.6 Hz, C’), 120.07 (dd, J = 291.6, 277.7 Hz, C’), 114.4 (C), 113.7, 64.7 (td, J = 24.9, 24.4, 20.9 Hz, C + C’), 55.4 (C), 55.3 (C’), 53.4 (dd, J = 25.7, 23.0 Hz, C), 53.1–52.7 (m, C’). 19 19F NMR (565 MHz, CDCl3, 25 °C) δ -77.9 (dt, J = 193.6, 10.6 Hz, 1F, F), -91.0 (ddd, J = 191.7, 12.7, 3.7 Hz, 1F, F’), -102.4 (dt, J = 192.1, 15.9 Hz, 1F, F), -119.2 (ddd, J = 193.6, 17.6, 13.7 Hz, 1F, F’).

[0075] Example 17:

[0076]

[0077] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (57.4 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (2 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 (50 / 1-5 / 1, v / v) to obtain the target compound G14 (56.1 mg, 72% yield, white solid). 1 H NMR (600MHz, CDCl3, 25℃) δ7.45–7.42(m,2H),7.32–7.27(m,1H),7.27–7.25(m,2H),7.16(dd,J=7.0,1.7Hz ,1H),7.13–7.09(m,2H),4.14–4.07(m,1H),3.97(td,J=13.5,7.3Hz,1H),3.94–3.79(m,1H),1.34(s,9H). 13 C NMR (151MHz, CDCl3, 25℃) δ160.6 (d, J = 6.0Hz), 151.6, 150.7, 129.5, 129.5, 127.2, 127.7, 126.0, 125.5, 120.3, 117.0 ,117.5(dd,J=297.1,275.5Hz),61.6(t,J=21.6Hz),47.3(dd,J=26.6,21.3Hz),34.7,32.7(dd,J=12.2,2.3Hz),31.4. 19 FNMR (565MHz, CDCl3, 25℃) δ76.9 (ddd, J=191.5, 13.1, 4.1Hz, 1F), 102.5 (dt, J=191.7, 14.0Hz, 1F).

[0078] Example 17:

[0079]

[0080] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (60.7 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol), and fac-(dFppy)3 (3 mg, 2 mol%) in dry DCM (2 mL). The tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 G15 (56.4 mg, 71% yield, colorless liquid). 1 H NMR (600MHz, CDCl3, 25℃) δ7.70(d,J=7.1Hz,1H),7.72(d,J=7.2Hz,1H),7.65–7.55(m,2H),7.47(dd,J=15.4,7.6Hz,3H) ,7.37–7.31(m,3H),4.79(dd,J=16.7,6.9Hz,1H),4.29–4.24(m,1H),3.70(ddd,J=15.1,12.0,6.7Hz,1H),1.37(s,9H). 13 C NMR (151MHz, CDCl3, 25℃) δ150.7, 147.7, 146.4, 139.9 (d, J = 2.7Hz), 137.5 (d, J = 5.9Hz), 132.4, 131.5, 127.4, 127.2, 125.6, 124.7, 123.9, 12 3.1,119.9(dd,J=295.5,277.7Hz),119.6,57.9(dd,J=23.4,21.3Hz),56.0(dd,J=26.4,23.1Hz),52.6,41.3(dd,J=16.0,2.7Hz),34.7,31.5. 19 F NMR (565MHz, CDCl3, 25℃) δ77.9 (ddd, J=191.4, 12.0, 4.9Hz, 1F), 103.2 (dt, J=191.3, 16.0Hz, 1F).

[0081] Example 19:

[0082]

[0083] In a glove box, a dry photoreactor tube equipped with a magnetic stirrer was charged with A (44.4 mg, 0.4 mmol, 2 equiv.), B (39.2 mg, 0.2 mmol), and [Ir(dF(CF3)ppy)2(dtbbpy)]PF6)3 (4.6 mg, 2 mol%) in dry DCM (2 mL). The photoreactor tube was sealed, removed from the glove box, and irradiated with a 6 W violet 400 nm LED light. 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 (100 / 1-50 / 1, v / v) to obtain the target compound G16 (49.2 mg, 70% yield, colorless liquid).

[0084] 1 H NMR (600MHz, CDCl3, 25℃) δ7.44–7.41(m,2H),7.20(d,J=7.1Hz,2H),4.06(td,J=11.9,6.1Hz,1H),3. 94(dddd,J=13.9,7.4,2.5,1.4Hz,1H),3.43(dtd,J=7.4,5.4,2.1Hz,1H),3.10(s,3H),1.33(s,9H). 13 C NMR (151MHz, CDCl3, 25℃) δ176.3,170.5(d,J=6.2Hz),151.7,127.9,127.9,125.9,116.0(dd,J=294.5,276 .1Hz), 55.7 (dd, J=24.9, 22.9Hz), 51.1 (dd, J=27.1, 24.1Hz), 36.3 (dd, J=12.3, 3.5Hz), 34.7, 31.4, 25.7. 19 F NMR (565MHz, CDCl3, 25℃) δ76.2–76.7(m,1F),101.2(dt,J=197.7,12.2Hz,1F).

[0085] App conversion:

[0086]

[0087] In a glove box, G1 (37.4 mg, 0.1 mmol) and B (27 mg, 0.25 mmol) in dried toluene (2 mL) were added to a dry photoreactor tube equipped with a magnetic stirrer. The photoreactor tube was sealed and removed from the glove box. The reaction mixture was stirred at room temperature for 12 hours. The crude product was purified by silica gel column chromatography (200-300 mesh) and eluted with PE (100 / 1-50 / 1, v / v) to obtain the target compound G17 (27.7 mg, colorless liquid, 70% yield).

[0088] 1 H NMR (600MHz, CDCl3, 25℃) δ7.97 (dd, J=7.0, 1.7Hz, 1H), 7.94–7.92 (m, 1H), 7.52–7.50 (m, 1H), 7.43–7.41 (m, 2H) ,7.34–7.27(m,5H),7.26–7.23(m,2H),4.57(dd,J=6.3,4.7Hz,1H),4.33(dd,J=13.7,4.7Hz,1H),1.27(s,9H). 13 C NMR (151MHz, CDCl3, 25℃) δ150.5, 146.4 (d, J = 356.1Hz), 134.4 (d, J = 6.4Hz), 132.7 (d, J = 4.9Hz), 131.7, 131.1, 131.0, 129.6, 127.2 (d, J = 5.1Hz) ,127.2,127.7,127.6,127.4,127.0(d,J=3.9Hz),125.5,124.1,123.7, 120.3(d,J=7.9Hz), 46.0(d,J=20.4Hz), 36.4(d,J=23.5Hz), 34.7, 31.3. 19 F NMR (565MHz, CDCl3, 25℃) δ-95.3 (dd, J=13.6, 6.4Hz).

[0089] The above description 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 principles of the present invention. These improvements and changes are also considered to be within the scope of protection of the present invention.

Claims

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

2. The difluorocyclobutane annular 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 difluorocyclobutane annular 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 difluorocyclobutane annular compound as claimed in any one of claims 1 to 3, characterized in that: The intracyclic olefin A and the difluoroolefin B, a catalyst and an organic solvent are mixed, and the mixture is stirred for reaction under light and at a temperature of -77°C to 170°C, and then separated and purified to obtain the difluorocyclobutane annular compound G.

5. The method for preparing the difluorocyclobutane annular compound according to claim 4, characterized in that: The molecular structural formula of the intracyclic olefin A is: The molecular structural formula of the difluoroolefin B is:

6. The method for preparing the difluorocyclobutane cyclopentane 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 difluorocyclobutane cyclopentane compound according to claim 6, characterized in that: 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.

8. The method for preparing the difluorocyclobutane annular 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.

9. The method for preparing the difluorocyclobutane annular compound according to claim 4, characterized in that: The molar ratio of the intracyclic olefin A to the difluoroolefin B is 1-2:1; the amount of the catalyst is 0.15% to 5% of the molar amount of the difluoroolefin B, and the concentration of the difluoroolefin B in the mixed solution is between 0.1M and 1M.

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

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