A bis-sulfur onium compound, its preparation method and application

Abstract

The application discloses a kind of double sulfur ylide compounds, its preparation method and application.The application discloses a kind of compound as shown in formula I: Wherein, m and n are independently 0, 1, 2, 3, 4 or 5;R 7 And R 8 Independently be C1~C6Alkyl, C1~C6Alkoxy, nitro or halogen;E is CO2R 9 ;R 9 C1~C6Alkyl.This double sulfur ylide compound can be used as the difluorocarbene precursor of photo initiation, can release difluorocarbene under room temperature and neutral blue light condition, can realize the gem difluorocyclopropanation reaction of olefin under photocatalysis and the difluoromethylation reaction of alcohol, provides important methodological support for the post modification of functional molecule in medicine, material and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of double sulfur leaf lid compound, its preparation method and application. BACKGROUND

[0002] The introduction of fluorine-containing functional groups can enhance the lipophilicity of molecules, promote their transmembrane transport, and effectively improve the metabolic stability and bioavailability of molecules with the pseudo effect and blocking effect of fluorine. Therefore, introducing fluorine atoms into biologically active molecules has become an important strategy in drug design (Chem. Rev. 2005, 105, 827). Among the many fluorine-containing groups, the difluoromethyl group (J. Org. Chem. 1995, 60, 1626) as an electronic equivalent of hydroxyl, the difluoromethylene group (J. Chem. Soc., Chem. Commun. 1981, 930) as an electronic equivalent of ether oxygen atom, and the gem-difluorovinyl group (J. Chem. Soc., Chem. Commun. 1989, 1437) as an electronic equivalent of carbonyl are also popular. The following formula shows an example of a proton pump inhibitor and an example of an ITK signaling pathway inhibitor (Drugs 2003, 63, 101; J. Med. Chem. 2015, 58, 3806), which shows that the introduction of a difluoromethylene building block into a drug molecule plays an important role in improving the biological activity of the molecule.

[0003]

[0004] Difluorocarbene is a reactive singlet electrophilic carbene, and is a common intermediate in fluorine chemistry. Introducing a difluoromethylene building block into various molecules with difluorocarbene is the most direct and efficient way to construct difluoromethyl, difluoromethylene and other functional groups at present. Therefore, scientists have developed a variety of difluorocarbene precursor reagents over the years, and have used them to complete a variety of reactions (Tetrahedron Lett. 2018, 59, 1301; Synthesis 2014, 46, 842). However, the existing difluorocarbene precursor reagents have a single activation mode, often requiring strong base or high temperature to initiate, so there are problems such as limited substrate range in application. Therefore, it is still of great significance to develop a more mild and efficient method for introducing a difluoromethylene building block. SUMMARY

[0005] The technical problem to be solved by the present application is to overcome the defects of the existing difluorocarbene precursor reagent, such as single activation mode, harsh initiation conditions, and narrow substrate range. To this end, the present application provides a double sulfur ylide compound, a preparation method and application thereof. The double sulfur ylide compound can be used as a photo-induced difluorocarbene precursor, and can release difluorocarbene under room temperature and neutral blue light conditions, and can realize the gem-difluorocyclopropanation reaction of olefins and the difluoromethylation reaction of alcohols under photocatalysis, thereby providing important methodological support for the post-modification of functional molecules in the fields of medicine, materials and the like.

[0006] The present application provides a compound as shown in formula I:

[0007]

[0008] wherein m and n are independently 0, 1, 2, 3, 4 or 5;

[0009] R 7 and R 8 are independently C1-C6 alkyl, C1-C6 alkoxy, nitro or halogen;

[0010] E is CO2R 9 ;

[0011] R 9 is C1-C6 alkyl.

[0012] In an embodiment, n and m are independently 0, 1 or 2, for example 0 or 1.

[0013] In an embodiment, the R 7 and R 8 are the same or different.

[0014] In an embodiment, the R 7 and R 8 , the halogen can be independently F, Cl, Br or I, preferably Cl.

[0015] In an embodiment, the R 7 and R 8 are independently -CH3, -OCH3, -NO2 or -Cl.

[0016] In an embodiment, the R 9 is methyl.

[0017] In an embodiment, the compound as shown in formula I is:

[0018] The present application provides a preparation method of a compound as shown in formula I, which comprises the following steps:

[0019] Step (1) is Method 1 or Method 2:

[0020] Method 1: subjecting a compound as shown in Formula II to the reaction as shown below in the presence of (trifluoromethyl)trimethylsilane and a base in an organic solvent to obtain a compound as shown in Formula III;

[0021] Method 2: subjecting a compound as shown in Formula II to the reaction as shown below in the presence of (triphenylphosphoniumyl) difluoroacetic acid inner salt in an organic solvent to obtain a compound as shown in Formula III;

[0022]

[0023] Step (2): subjecting a compound as shown in Formula III and a compound as shown in Formula IV to the reaction as shown below in the presence of a catalyst in an organic solvent to obtain a compound as shown in Formula I;

[0024]

[0025] wherein, R 7 , R 8 , m, n, E and R 9 are as defined in any one of the present application.

[0026] In an embodiment, in Method 1, the organic solvent can be an amide solvent (such as N,N-dimethylformamide and / or N,N-dimethylacetamide), preferably N,N-dimethylformamide.

[0027] In an embodiment, in Method 1, the base can be one or more of lithium tert-butoxide, potassium tert-butoxide and sodium tert-butoxide, preferably lithium tert-butoxide.

[0028] In an embodiment, in Method 1, the molar ratio of the base to the compound as shown in Formula II can be a conventional molar ratio in the art, preferably 1.5:1-5:1, more preferably 2:1-4:1 (such as 3:1).

[0029] In an embodiment, in Method 1, the molar ratio of the (trifluoromethyl)trimethylsilane to the compound as shown in Formula II can be a conventional molar ratio in the art, preferably 1.5:1-3:1, more preferably 1.5:1-2.5:1 (such as 2:1).

[0030] In an embodiment, in Method 1, the molar concentration of the compound as shown in Formula II in the organic solvent can be a conventional molar concentration in the art, preferably 0.2-1.2 mol / L, more preferably 0.5-1 mol / L (such as 0.8 mol / L).

[0031] In an embodiment, in Method 1, the temperature of the reaction can be a conventional reaction temperature in the art, preferably 0-40 °C, more preferably 20-30 °C.

[0032] In an embodiment, in Method 2, the organic solvent can be an ether solvent (e.g., dioxane), preferably 1,4-dioxane.

[0033] In an embodiment, in Method 2, the molar ratio of the (triphenylphosphoranylidene) difluoroacetic acid inner salt to the compound of Formula II can be a conventional molar ratio in the art, preferably 1.2:1-3:1, more preferably 1.2:1-2.5:1 (e.g., 2:1 or 1.4:1).

[0034] In an embodiment, in Method 2, the molar concentration of the compound of Formula II in the organic solvent can be a conventional molar concentration in the art, preferably 0.1-1.2 mol / L, more preferably 0.1-1 mol / L (e.g., 0.125 mol / L).

[0035] In an embodiment, in Method 2, the temperature of the reaction can be a conventional reaction temperature in the art, preferably 0-80 °C, more preferably 55-65 °C.

[0036] In an embodiment, in Method 1 or Method 2, the reaction can be carried out under nitrogen or inert gas protection, preferably under argon protection.

[0037] In an embodiment, in step (2), the organic solvent can be a conventional organic solvent in the art, which can also be a halogenated hydrocarbon solvent (e.g., one or more of dichloromethane, chloroform, and 1,2-dichloroethane) and / or an aromatic solvent (e.g., one or more of toluene, xylene, chlorobenzene, and trifluorotoluene), preferably dichloromethane and / or toluene, more preferably dichloromethane.

[0038] In an embodiment, in step (2), the catalyst can be one or more of Rh2(esp)2, Rh2(OAc)4, and Rh2(C7H 15 CO2)4, preferably Rh2(esp)2or Rh2(C7H 15 CO2)4.

[0039] In an embodiment, in step (2), the molar ratio of the catalyst to the compound of Formula III can be a conventional molar ratio in the art, preferably (0.5-2):100, more preferably (0.8-1.5):100 (e.g., 1:100).

[0040] In an embodiment, in step (2), the molar ratio of the compound of formula IV to the compound of formula III can be a conventional molar ratio in the art, preferably 1.5:1-5:1, more preferably 2:1-4:1 (e.g. 3:1 or 4:1).

[0041] In an embodiment, in step (2), the molar concentration of the compound of formula III in the organic solvent can be a conventional molar concentration in the art, preferably 0.02-0.2 mol / L, more preferably 0.05-0.15 mol / L (e.g. 0.1 mol / L).

[0042] In an embodiment, in step (2), the temperature of the reaction can be a conventional temperature of the reaction in the art, preferably 0-40℃, more preferably 20-30℃.

[0043] In an embodiment, in step (2), the reaction can be carried out under the protection of nitrogen or inert gas, preferably under the protection of argon.

[0044] In an embodiment, in step (2), the compound of formula IV is slowly added dropwise to the solution of the compound of formula III and the organic solvent.

[0045] The present application also provides any one of the following compounds:

[0046] The present application also provides the use of a compound of formula I as described above in an organic synthesis reaction, which is a gem-difluorocyclopropanation reaction of an olefin or a difluoromethylation reaction of an alcohol.

[0047] In an embodiment, the gem-difluorocyclopropanation reaction of an olefin comprises the following steps:

[0048] In an organic solvent, in the presence of a catalyst and a compound of formula I, a compound containing a fragment of formula V undergoes gem-difluorocyclopropanation reaction under blue light irradiation to obtain a compound containing a fragment of formula Va;

[0049]

[0050] E, m, n, R 7 and R 8 are as defined in any one of the present application.

[0051] In an embodiment, the difluoromethylation reaction of an alcohol comprises the following steps:

[0052] In the presence of a catalyst and a compound of Formula I, a compound containing a moiety of Formula VI is difluoromethylated under blue light irradiation to give a compound containing a moiety of Formula VIb;

[0053]

[0054] In one embodiment, the gem-difluorocyclopropanation reaction of an olefin comprises the following steps:

[0055] In the presence of a catalyst and a compound of Formula I, a compound of Formula VII is subjected to gem-difluorocyclopropanation reaction of an olefin under blue light irradiation in an organic solvent to give a compound of Formula VIIa;

[0056]

[0057] wherein R 1 is

[0058] R 3 is hydrogen or C1-C6 alkyl;

[0059] Alternatively, R 3 and R 1 together with the atom to which they are attached form a 9-18 membered aromatic ring;

[0060] Ring A is a 6-20 membered aromatic ring;

[0061] R 5 is independently C1-C6 alkyl, C1-C6 alkyl substituted with one or more R 5-1 , C1-C6 alkoxy, -COOC1-C6 alkyl, 6-10 membered aryl, -NR b R c , halogen, cyano, oxo or thioxo;

[0062] R 5-1 is independently 5-10 membered heteroaryl substituted with one or more R 5-1-1 , C1-C6 alkoxy, -NR b R c , halogen or cyano; in said 5-10 membered heteroaryl, the heteroatoms are selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0063] R 5-1-1 is independently oxo;

[0064] R b and R c are independently C1-C6 alkyl;

[0065] k is 0, 1 or 2;

[0066] R 2 is hydrogen, C1-C6alkyl or -OC(O)-C1-C6alkyl;

[0067] R 4 is hydrogen or C1-C6alkyl.

[0068] In one embodiment, the difluoromethylation of the alcohol comprises the steps of:

[0069] In one embodiment, the difluoromethylation of the compound of formula VIII comprises the steps of:

[0070]

[0071] wherein L is C1-C6alkylene or * -COOC1-C6alkylene- attached to ring B via the *-end;

[0072] ring B is a 6-10 membered aromatic ring or a 5-10 membered heteroaromatic ring, wherein the heteroatoms are selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3;

[0073] R 6 independently C1-C6alkyl, C1-C6alkoxy, halogen or cyano;

[0074] t is 0, 1, 2 or 3.

[0075] In one embodiment, ring A is a phenyl ring or

[0076] In one embodiment, R 2 , R 3 , R 4 , R 5 , R b and R c , the C1-C6alkyl groups can independently be C1-C4alkyl, such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl or t-butyl, preferably methyl.

[0077] In one embodiment, R 5 and R 5-1 , the C1-C6alkoxy groups can independently be C1-C4alkoxy, such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, sec-butoxy or t-butoxy, preferably methoxy.

[0078] In one embodiment, R5 and R 5-1 In the above, the halogen can be F, Cl, Br or I, preferably Br.

[0079] In one embodiment, R 5 In the above, the 6-10 membered aryl can be phenyl.

[0080] In one embodiment, when R 3 and R 1 together with the atoms to which they are attached form a 9-18 membered aromatic ring, the 9-18 membered aromatic ring can be a 9-12 membered aromatic ring, preferably

[0081] In one embodiment, the k is 0 or 1.

[0082] In one embodiment, the compound of Formula VII is

[0083] In some embodiments, in the gem-difluorocyclopropanation reaction of an olefin, the catalyst can be one or more of Ir(ppy)3, Ir(p- t Bu-ppy)3, Ru(bpy)3(PF6)2, and Rhodamine 6G, preferably Ir(ppy)3 and / or Ir(p- t Bu-ppy)3.

[0084] In some embodiments, in the gem-difluorocyclopropanation reaction of an olefin, the molar ratio of the catalyst to the compound of Formula VII can be (0.05-2): 100 (e.g., 0.05: 100, 0.2: 100, 0.5: 100, 1: 100, or 2: 100), preferably (0.5-2): 100.

[0085] In one embodiment, in the gem-difluorocyclopropanation reaction of an olefin, the molar ratio of the compound of Formula I to the compound of Formula VII is (1-2.5): 1 (e.g., 1: 1, 1.5: 1, 2: 1, or 2.5: 1); preferably (1.5-2.5): 1.

[0086] In one embodiment, in the gem-difluorocyclopropanation reaction of an olefin, the organic solvent is one or more of a nitrile solvent (e.g., acetonitrile), a ketone solvent (e.g., acetone), a halogenated alkane solvent (e.g., dichloromethane), an ether solvent (e.g., tetrahydrofuran), and an aromatic solvent (e.g., toluene), preferably an aromatic solvent.

[0087] In an embodiment, in the gem-difluorocyclopropanation reaction of the olefin, the volume molar ratio of the organic solvent to the compound of formula VII is 5 mL / mmol to 20 mL / mmol (e.g., 10 mL / mmol); preferably 5 mL / mmol to 15 mL / mmol.

[0088] In an embodiment, in the gem-difluorocyclopropanation reaction of the olefin, the temperature of the gem-difluorocyclopropanation reaction of the olefin is 10°C to 40°C; preferably 20°C to 30°C.

[0089] In an embodiment, in the gem-difluorocyclopropanation reaction of the olefin, the wavelength of the blue light is 463 nm to 475 nm, e.g., a blue light LED.

[0090] In an embodiment, in L, the C1-C6 alkylene group can be a C1-C4 alkylene group, e.g., -CH2-, -CH2CH2-, -CH(CH3)-, -CH2CH2CH2-, -CH(CH3)CH2-, -C(CH3)2-, -CH2CH2CH2CH2-, -CH(CH3)CH2CH2-, -CH2CH(CH3)CH2-, or -CH2C(CH3)2-, preferably -CH2-, -CH2CH2-, -CH(CH3)-, or -CH2CH2CH2-.

[0091] In an embodiment, in L, the C1-C6 alkylene group can be a C1-C4 alkylene group, e.g., -CH2-, -CH2CH2-, -CH(CH3)-, -CH2CH2CH2-, -CH(CH3)CH2-, -C(CH3)2-, -CH2CH2CH2CH2-, -CH(CH3)CH2CH2-, -CH2CH(CH3)CH2-, or -CH2C(CH3)2-, preferably -CH2-, -CH2CH2-, -CH(CH3)-, or -CH2CH2CH2-. * -COOC1-C6 alkylene group can be a * -COOC1-C4 alkylene group, e.g., -COO-CH2-, * -COO-CH2-, * -COO-CH2CH2-, * -COO-CH(CH3)-, * -COO-CH2CH2CH2-, * -COO-CH(CH3)CH2-, * -COO-C(CH3)2-, * -COO-CH2CH2CH2CH2-, * -COO -CH(CH3)CH2CH2-, * -COO -CH2CH2CH(CH3)-, * - -CH2CH(CH3)CH2-, or * -COO-CH2C(CH3)2-, preferably * -COO-CH2CH2CH(CH3)-.

[0092] In an embodiment, in ring B, the 6-18 membered aromatic ring can be a 6-10 membered aromatic ring, preferably a benzene ring or a naphthalene ring.

[0093] In certain embodiments, in ring B, the 5-10 membered heteroaromatic ring can be a 5-6 membered heteroaromatic ring, preferably

[0094] In certain embodiments, R 6 In certain embodiments, the C1-C6 alkyl group can be independently a C1-C4 alkyl group, such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, or t-butyl, preferably methyl.

[0095] In certain embodiments, R 6 In certain embodiments, the C1-C6 alkoxy group can be independently a C1-C4 alkoxy group, such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, or t-butoxy, preferably methoxy.

[0096] In certain embodiments, R 6 In certain embodiments, the halogen can be F, Cl, Br, or I, preferably Br.

[0097] In certain embodiments, t is 0, 1, or 2.

[0098] In certain embodiments, the compound of Formula VIII is

[0099] In some embodiments, in the difluoromethylation reaction of an alcohol, the catalyst is fac-Ir(ppy)3.

[0100] In some embodiments, in the difluoromethylation reaction of an alcohol, the molar ratio of the catalyst to the compound of Formula VIII can be (0.05-0.5):100 (e.g., 0.05:100, 0.1:100, 0.3:100, or 0.5:100), preferably (0.1-0.5):100.

[0101] In certain embodiments, in the difluoromethylation reaction of an alcohol, the molar ratio of the compound of Formula I to the compound of Formula VIII can be (1-2):1 (e.g., 1:1, 1.5:1, or 2:1); preferably (1.5-2):1.

[0102] In certain embodiments, in the difluoromethylation reaction of an alcohol, the difluoromethylation reaction can be performed in the presence of water, and the molar ratio of the water to the compound of Formula VIII can be (0-4):1 (e.g., 0.5:1, 1:1, 2:1, or 4:1); preferably (1-4):1.

[0103] In an embodiment, the solvent in the difluoromethylation reaction of an alcohol is one or more of a nitrile solvent (e.g., acetonitrile), a halogenated alkane solvent (e.g., dichloromethane), an ether solvent (e.g., tetrahydrofuran), an amide solvent (e.g., N,N-dimethylformamide), and an aromatic solvent (e.g., toluene), preferably an aromatic solvent.

[0104] In an embodiment, the volume mole ratio of the solvent to the compound of Formula VIII in the difluoromethylation reaction of an alcohol is 5 mL / mmol to 20 mL / mmol (e.g., 10 mL / mmol); preferably 5 mL / mmol to 15 mL / mmol.

[0105] In an embodiment, the temperature of the difluoromethylation reaction of an alcohol is 10 °C to 40 °C; preferably 20 °C to 30 °C.

[0106] In an embodiment, the wavelength of the blue light in the difluoromethylation reaction of an alcohol is 463 nm to 475 nm, e.g., a blue LED.

[0107] The present application also provides any one of the following compounds:

[0108]

[0109] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this application belongs.

[0110] In the present specification, groups and substituents thereof can be chosen by one of ordinary skill in the art to provide stable moieties and compounds. As used herein, the term "substituted" means that any one or more hydrogen atoms on a group is replaced by a substituent independently selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, alkylamino, aryl, arylalkyl, araloxy, aryloxyalkyl, arylalkyloxyalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, acyl, carboxyl, carboxyl ester, carboxyl ester alkyl, carboxyl ester amino, acylamino, acyloxy, amino, aminoacyl, aminoalkyl, aminocarbonyl, aminooxy, azido, cyano, hydroxyl, hydroxyalkyl, imino, ketone, nitro, thiol, thioalkyl, oxime, oxime ester, oxime amide, and combinations thereof.

[0111] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in this application, including but not limited to patents, patent applications, articles, books, treatises and web pages, are hereby expressly incorporated by reference in their entirety.

[0112] Certain chemical groups defined herein are preceded by a simplified symbol that indicates the total number of carbon atoms in the group. For example, C1-C6alkyl means an alkyl group as defined below having a total of 1, 2, 3, 4, 5, or 6 carbon atoms. The total number of carbon atoms in the simplified symbol does not include carbon that can be present in substituents of the group.

[0113] In addition to the foregoing, as used in the specification and the claims, the following terms shall have the meanings indicated below, unless otherwise indicated.

[0114] In the present application, the term "halogen" means fluorine, chlorine, bromine or iodine.

[0115] In the present application, the term "alkyl" as a group or part of a group (for example, in the groups halo-substituted alkyl and the like) is meant to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the indicated number of carbon atoms; for example, C1-C6. As defined in "C1-C6 alkyl" includes groups having 1, 2, 3, 4, 5, or 6 carbon atoms in a straight or branched arrangement. For example, in the present application, the C1-C6 alkyl groups are each independently methyl, ethyl, propyl, butyl, pentyl, or hexyl; wherein propyl is a C3 alkyl group (including isomers, for example, n-propyl or isopropyl); butyl is a C4 alkyl group (including isomers, for example, n-butyl, sec-butyl, isobutyl, or t-butyl); pentyl is a C5 alkyl group (including isomers, for example, n-pentyl, 1-methyl-butyl, 1-ethyl-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, isopentyl, t-pentyl, or neopentyl); and hexyl is a C6 alkyl group (including isomers, for example, n-hexyl or isohexyl).

[0116] The term "alkoxy" means the group R X -O-, R X is defined as the term "alkyl".

[0117] In the present application, the term "aryl" as a group or part of a group means a group having 6-10 ring atoms and providing a 4n+2 aromatic ring system (for example, having 6 or 10 shared p-electrons in a cyclic array) in a monocyclic or polycyclic (for example, bicyclic) aromatic ring system having zero heteroatoms provided in the aromatic ring system ("C6-C 14 Examples of the above aryl units include phenyl or naphthyl.

[0118] In the present application, the term "heteroaryl" as a group or as part of a group refers to a 5-7 membered monocyclic or 8-10 membered (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system having ring carbon atoms and from 1-3 ring heteroatoms (where each heteroatom is independently selected from nitrogen, oxygen, and sulfur) provided in the aromatic ring system ("5-10 membered heteroaryl"). In heteroaryl groups containing one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valence permits. Heteroaryl bicyclic ring systems can include one or more heteroatoms in one or both rings. Thus, fused ring systems including a heteroaryl ring fused with one or more of the aryl groups as defined above (where the fusion is either on the aryl or on the heteroaryl ring), and in such cases the number of ring members is the number of ring members in the fused (aryl / heteroaryl) ring system. In bicyclic heteroaryl groups where one ring does not include a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, etc.), the point of attachment can be on either ring, i.e., either the ring bearing a heteroatom (e.g., 2-indolyl) or the ring not containing a heteroatom (e.g., 5-indolyl). The nitrogen, carbon, or sulfur atoms in "heteroaryl" can be optionally oxidized; the nitrogen atoms can be optionally quaternized. Exemplary heteroaryl groups within the scope of this definition include, but are not limited to: pyrrolyl, furanyl, thiophenyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, furazanyl, oxatriazolyl. Exemplary 6-membered heteroaryl groups include, but are not limited to: pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, triazinyl, or tetrazinyl. Exemplary 5,5 bicyclic heteroaryl groups include, but are not limited to, thienothienyl, thienofuranyl, thienopyrrolyl, thienoxazolyl, thienothiazolyl, thienoimidazolyl, imidazothiazolyl, or pyrazoxazolyl. Exemplary 5,6-bicyclic heteroaryl groups include, but are not limited to: indolyl, isoindolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, isobenzofuranyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzoimidazolyl, indazolyl, isoindazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, indolizinyl, pyrrolopyridyl, pyridooxazolyl, pyridothiazolyl, imidazopyridazinyl, imidazopyrazinyl, pyridylimidazolyl, triazolopyridazinyl, triazolopyrazinyl, triazolopyrimidinyl, triazolopyridinyl, pyridothiazolyl, tetrazolopyridinyl, or purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to: quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, quinazolinyl, naphthyridinyl, pyridopyrimidine, pyrazinopyridazine, or pteridinyl. Exemplary tricyclic heteroaryl groups include, but are not limited to: carbazolyl, dibenzofuranyl, carbolinyl, acridinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, bipyridyl, or terthiophenyl.

[0119] As used herein, the term "halogen" means fluorine, chlorine, bromine, iodine or astatine.

[0120] As used herein, the term "cyano" means -CN.

[0121] As used herein, the term "nitro" means -NO2.

[0122] As used herein, the term "oxo" means =O.

[0123] As used herein, the term "thioxo" means =S.

[0124] As used herein, the term "aromatic ring" means any stable monocyclic or bicyclic carbocyclic ring of up to 7 atoms in each ring, at least one of which is aromatic. Examples of such aromatic ring units include benzene, naphthalene, tetrahydronaphthalene, indane, biphenyl, phenanthrene, anthracene or acenaphthyl. It is understood that where the aryl substituent is a bicyclic substituent and one of the rings is non-aromatic, attachment is through the "aromatic ring".

[0125] As used herein, the term "heteroaromatic ring" means a stable monocyclic or bicyclic ring of up to 7 atoms in each ring, at least one of which is aromatic and which contains from 1 to 4 heteroatoms selected from O, N, and S. Heteroaromatic rings within the scope of this definition include, but are not limited to: acridine, carbazole, cinnoline, carbolin, quinoxaline, imidazole, pyrazole, pyrrole, indole, indoline, benzotriazole, benzimidazole, furan, thiophene, isothiazole, benzothiophene, dihydrobenzothiophene, benzofuran, isobenzofuran, benzoxazole, benzofurazan, benzopyrazole, quinoline, isoindole, isoquinoline, oxazole, oxadiazole, isoxazole, indole, pyrazine, pyridopyridine, tetrazolopyridine, pyridazine, pyridine, naphthpyrimidine, pyrimidine, pyrrole, tetrazole, thiadiazole, thiazole, thiophene, triazole, quinazoline, tetrahydroquinoline, dihydrobenzimidazole, dihydrobenzofuran, dihydrobenzoxazole, dihydroquinoline. As with the definition of heterocycle below, "heteroaromatic ring" is also understood to include N-oxide derivatives of any nitrogen-containing heteroaromatic ring. In the case where the heteroaryl substituent is a bicyclic substituent and one of the rings is non-aromatic or does not contain a heteroatom, it is understood that attachment is through the aromatic ring or through the heteroatom of the containing ring, respectively.

[0126] The terms "moiety," "group," as used herein refer to a specific fragment or functional group in a molecule.

[0127] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this application belongs. If there is an inconsistency between the definitions of terms as defined in this document and as used in the prior art, the definition as used in this document shall control.

[0128] It should be understood that the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0129] On the basis of common general knowledge in the art, the above-mentioned preferred conditions can be combined arbitrarily, i.e. to obtain each preferred example of the present application.

[0130] The reagents and raw materials used in the present application are commercially available.

[0131] The positive progress effect of the present application is that the difluoromethylene reagent shown in formula I can realize the gem-difluorocyclopropanation reaction of olefins and the difluoromethylation reaction of alcohols under photocatalysis. The reagent can be used as a photo-initiated difluorocarbene precursor, can release difluorocarbene under room temperature and neutral blue light conditions, and provides important methodological support for the late-stage modification of functional molecules in the fields of medicine, materials and the like. DETAILED DESCRIPTION

[0132] The present application will be further described by way of examples, but the present application is not limited to the scope of the examples. The experimental methods in the following examples are not specified, and are selected according to conventional methods and conditions, or according to the instructions of the goods.

[0133] Example 1 Synthesis of bis-sulfur ylide difluoromethylene reagent (reagent 1)

[0134]

[0135] Diphenyl disulfide (21.8 g, 100 mmol) was weighed in a 350 mL Schlenk flask with a stirrer, and argon was exchanged three times. Lithium tert-butoxide (24.0 g, 300 mmol) was weighed in the system in a glove box, and after adding super-dry DMF (120 mL), the system was stirred at room temperature for 5 min. TMSCF3 (29.6 mL, 200 mmol) was added dropwise to the system under argon protection, and after the dropwise addition was completed, the system was stirred at room temperature for 1 h. After the reaction was completed, an appropriate amount of hydrochloric acid (1 M) was added to quench the reaction, and ethyl acetate was extracted. The combined organic layers were dried over anhydrous sodium sulfate, filtered, concentrated by rotary evaporation, and purified by flash column chromatography (petroleum ether) to obtain the product as a colorless transparent liquid (17.1 g, 64%).

[0136] 1 H NMR (400 MHz, CDCl3, 293 K, TMS) δ 7.61 (d, J = 7.1 Hz, 4H), 7.45 (t, J = 7.3 Hz, 2H), 7.38 (t, J = 7.9 Hz, 4H); 19 F NMR (376 MHz, CDCl3) δ -49.04 (s, 2F); 13C NMR (151 MHz, CDC13, 293 K, TMS) δ 136.15, 132.24 (t, J = 314.1 Hz), 130.17, 129.09, 127.30 ppm. IR (KBr): v max = 3062, 1475, 1441, 1042, 1023, 888, 748, 689, 517, 503 cm -1 MS (EI): 159 (100), 268. HRMS (EI): calcd for C 13 H 10 F2S2: 268.0186, found: 268.0190.

[0137]

[0138] Rh2(esp)2(191 mg, 0.250 mmol) was weighed into a 350 mL Schlenk flask with a stir bar, and was purged with argon three times. The thioether prepared in the previous step (6.71 g, 25.0 mmol) was dissolved in super dry dichloromethane (250 mL), and then the nitrene (11.9 g, 75.0 mmol) was added slowly dropwise into the system. After the dropwise addition was completed, the system was stirred at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the crude product was obtained by flash column chromatography (petroleum ether: ethyl acetate = 1:5). The product was recrystallized from a small amount of dichloromethane into a large amount of diethyl ether, and was obtained by suction filtration as a light yellow solid (11.3 g, 85%, dr = 2:1).

[0139] Mp: 110-112 °C. 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.85 (d, J = 8.1 Hz, 2H), 7.76 (d, J = 7.7 Hz, 4H), 7.63-7.59 (m, 3H), 7.56-7.50 (m, 6H), 3.70 (s, 6H, minor isomer), 3.69 (s, 12H, major isomer); 19 F NMR (376 MHz, CDC13) δ -55.60 (d, J = 128.1 Hz, 1F, major isomer), -61.19 (s, 1F, minor isomer), -64.30 (d, J = 128.1 Hz, 1F, major isomer); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 165.69, 165.61, 133.23, 133.02, 131.62 (dd, J = 372.4, 367.9 Hz), 130.25, 130.19, 130.14, 129.48, 127.80 (t, J = 373.4 Hz), 126.46, 126.20, 56.04, 55.73, 51.67 ppm. IR (KBr): v max = 3072, 2946, 1729, 1697, 1667, 1438, 1323, 1242, 1085, 766, 525 cm -1 MS (ESI): 551.1 (M + + Na). HRMS (ESI): calcd for C 23 H 22 O8F2NaS2: 551.06164 (M + + Na), found: 551.06108.

[0140] Example 2 Synthesis of methoxy substituted bisthioylide reagent

[0141]

[0142] The dithioether (4.18 g, 15.0 mmol) was weighed into a 100 mL Schlenk flask with a stir bar, and was purged with argon three times. Lithium tert-butoxide (3.60 g, 45.0 mmol) was weighed into the system in a glove box, and after the addition of super dry DMF (18.0 mL), the reaction was stirred at room temperature for 5 min. TMSCF3(4.43 mL, 30.0 mmol) was added dropwise into the system under argon protection, and after the dropwise addition was completed, the system was stirred at room temperature for 1 h. After the reaction was completed, an appropriate amount of hydrochloric acid (1 M) was added to quench the reaction, and ethyl acetate was used for extraction. The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation. The product was obtained as a light yellow transparent liquid (1.9 g, 38%) by flash column chromatography (petroleum ether: ethyl acetate = 50: 1).

[0143] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.50 (d, J = 8.7 Hz, 4H), 6.88 (d, J = 8.7 Hz, 4H), 3.81 (s, 6H); 19 F NMR (376 MHz, CDC13) δ -51.00 (s, 2F); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 161.31, 138.12, 132.21 (t, J = 313.9 Hz), 117.88, 114.57, 55.33 ppm. IR (KBr): v max = 3006, 2838, 1592, 1495, 1293, 1174, 1030, 889, 828, 529 cm -1 MS (EI): 189 (100), 328. HRMS (EI): calcd for C 15 H 14 O2F2S2: 328.0398, found: 328.0403.

[0144]

[0145] Rh2(esp)2(31.0 mg, 0.0400 mmol) was weighed into a 100 mL Schlenk flask with a stir bar, and was purged with argon three times. The thioether (1.31 g, 4.00 mmol) prepared in the previous step was added to the flask, and was dissolved in super-dry dichloromethane (40.0 mL). The system was then purged with argon three times, and the diazene (1.90 g, 12.0 mmol) was added dropwise to the system. After the dropwise addition was completed, the system was stirred at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the crude product was obtained by flash column chromatography (petroleum ether: ethyl acetate = 1:5). The product was recrystallized from a small amount of dichloromethane and a large amount of diethyl ether, and was obtained as a white solid (1.9 g, 80%, dr = 2:1).

[0146] Mp: 84-86 °C. 1 H NMR (500 MHz, CDC13, 293 K, TMS) δ 7.81 (d, J = 9.0 Hz, 2H), 7.74 (d, J = 9.0 Hz, 4H), 6.95-6.90 (m, 6H), 3.78 (s, 6H), 3.77 (s, 3H), 3.62 (s, 12H, major isomer), 3.62 (s, 6H, minor isomer); 19 F NMR (376 MHz, CDC13) δ -58.59 (d, J = 132.1 Hz, 1F, major isomer), -62.43 (s, 1F, minor isomer), -65.55 (d, J = 132.1 Hz, 1F, major isomer); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 165.57, 165.52, 163.48, 163.41, 133.10, 132.58, 130.47 (dd, J = 368.4, 364.0 Hz), 127.37 (t, J = 369.7 Hz), 116.42, 115.96, 115.37, 115.28, 57.77, 57.34, 55.50, 51.25 ppm. IR (KBr): v max = 2950, 2842, 1728, 1698, 1663, 1590, 1435, 1313, 1181, 1087, 770, 733, 530 cm -1 MS (ESI): 611.1 (M + + Na). HRMS (ESI): calc. for C 25 H 26 O 10 F2NaS2: 611.08277 (M + + Na), found: 611.08250.

[0147] Example 3 Synthesis of chloro-substituted bisthioylidene reagent

[0148]

[0149] The dithioether (4.31 g, 15.0 mmol) was weighed into a 100 mL Schlenk flask with stirring, and was replaced with argon three times. The lithium tert-butoxide (3.60 g, 45.0 mmol) was weighed into the system in a glove box, and after the addition of super dry DMF (18.0 mL), the reaction was stirred at room temperature for 5 min. Under the protection of argon, TMSCF3 (4.43 mL, 30.0 mmol) was added dropwise into the system, and after the dropwise addition was completed, the system was stirred at room temperature for 1 h. After the reaction was completed, an appropriate amount of hydrochloric acid (1 M) was added to quench the reaction, and ethyl acetate was used for extraction. The organic layers were combined, dried with anhydrous sodium sulfate, filtered, concentrated by rotary evaporation, redissolved in a small amount of ethyl acetate, and poured into a large amount of petroleum ether to obtain the product as a white needle-shaped solid (3.1 g, 61%).

[0150] Mp: 132-134 °C. 1 H NMR (500 MHz, CDC13, 293 K, TMS) δ 7.55-7.52 (m, 4H), 7.40-7.38 (m, 4H); 19 F NMR (376 MHz, CDC13) δ -49.43 (s, 2F); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 137.46, 137.07, 131.82 (t, J = 315.3 Hz), 129.50, 125.49 ppm. IR (KBr): v max = 3087, 1571, 1475, 1389, 1092, 1045, 1023, 873, 823, 504 cm -1 MS (EI): 193 (100), 336. HRMS (EI): calcd for C 13 H8Cl2F2S2: 335.9407, found: 335.9406.

[0151]

[0152] Rh2(esp)2(31.0 mg, 0.0400 mmol) was weighed into a 100 mL Schlenk flask with a stir bar, and was purged with argon three times. The thioether (1.35 g, 4.00 mmol) prepared in the previous step was added to the flask, and was dissolved in super-dry dichloromethane (40.0 mL). The system was then purged with argon three times, and the diazene (1.90 g, 12.0 mmol) was added dropwise to the system. After the dropwise addition was completed, the system was stirred at room temperature for 24 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the crude product was obtained by flash column chromatography (petroleum ether: ethyl acetate = 1:5). The product was recrystallized from a small amount of dichloromethane and a large amount of diethyl ether, and was obtained as a light yellow solid (1.4 g, 57%, dr = 2:1) after filtration.

[0153] Mp: 121-123 °C. 1 H NMR (500 MHz, CDC13, 293 K, TMS) δ 7.77 (d, J = 8.5 Hz, 2H), 7.70 (d, J = 8.5 Hz, 4H), 7.49-7.45 (m, 6H), 3.66 (s, 6H, minor isomer), 3.65 (s, 12H, major isomer); 19 F NMR (376 MHz, CDC13) δ -55.96 (d, J = 129.7 Hz, 1F, major isomer), -60.08 (s, 1F, minor isomer), -63.58 (d, J = 129.6 Hz, 1F, major isomer); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 165.50, 165.42, 140.29, 140.05, 131.65, 131.28 (dd, J = 370.4, 371.7 Hz), 131.09, 130.50, 130.45, 127.98 (t, J = 374.2 Hz), 124.56, 124.35, 56.22, 56.06, 51.77 ppm. IR (KBr): v max = 3412, 2949, 1702, 1671, 1645, 1432, 1325, 1294, 1088, 822, 766, 503 cm -1 MS (ESI): 619.0 (M + + Na). HRMS (ESI): calcd for C 23 H 20 O8F2NaS2Cl2: 618.98369 (M + + Na), found: 618.98378.

[0154] Example 4 Synthesis of methyl and nitro substituted bisthioazomethine reagent

[0155]

[0156] In a dry 250 mL round bottom flask with stirring bar, p-nitrothiophenol (4.70 g, 30.0 mmol), p-toluenesulfonyl chloride (17.2 g, 90.0 mmol) and 120 mL acetonitrile were added, then triphenylphosphine (47.2 g, 180 mmol) was added slowly, then the round bottom flask was placed in an oil bath at 80 °C and stirred for 3 h. After the reaction was completed, it was cooled to room temperature, the magnetic bar was removed, the solvent was removed under reduced pressure, and then the solid was extracted with petroleum ether / ethyl ether (1:1) 500 mL, concentrated, and purified by flash column chromatography (petroleum ether: ethyl acetate = 20:1) to give a yellow solid 6.5 g, yield 79%.

[0157] 1 H NMR (500 MHz, CDC13, 293 K, TMS) δ 8.16 (d, J = 8.9 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 2.33 (s, 3H); 13 C NMR (126 MHz, CDC13, 293 K, TMS): δ 146.60, 146.51, 138.58, 132.04, 130.27, 128.80, 126.26, 124.23, 21.22 ppm.

[0158]

[0159] In a dry 250 mL Schlenk flask with stir bar, 1-(4-nitrophenyl)-2-(p-tolyl)disulfane (2.80 g, 10.0 mmol), PDFA (7.10 g, 20.0 mmol), 80.0 mL 1,4-dioxane were added and stirred at 60 °C in an oil bath for 12 h. After the reaction was completed, the mixture was cooled to room temperature, diluted with 200 mL water, extracted with ethyl acetate (100 mL x 3), the organic phase was combined, back-extracted with 100 mL water, separated, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash column chromatography (petroleum ether: ethyl acetate = 20: 1) to give 1.1 g of yellow solid, yield 36%.

[0160] 1 H NMR (500 MHz, CDC13, 293 K, TMS) δ 8.21 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 7.9 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 2.39 (s, 3H); 19 F NMR (376 MHz, CDC13, 293 K, TMS) δ -48.57 ppm (s, 2F); 13 C NMR (126 MHz, CDC13, 293 K, TMS): δ 148.56, 141.34, 136.47, 136.34, 135.40, 132.18 (t, J = 315.5 Hz), 130.24, 124.05, 123.14, 21.50 ppm. IR (KBr): v max = 3096, 1600, 1523, 1347, 1045, 885, 852, 809 cm -1 MS (DART): 328.0 (M + +H). HRMS (DART): calcd for C 14 H 12 O2NF2S2: 328.0272 (M + +H), found: 328.0273.

[0161]

[0162] Rhodium (II) octanoate dimer (15.0 mg, 0.0200 mmol) was weighed into a 50 mL Schlenk flask with stirring, and was degassed with argon three times. (Difluoro((4-nitrophenyl)thio)methyl)(p-tolyl)sulfane (0.654 g, 2.00 mmol) was dissolved in super dry dichloromethane (20.0 mL), and then the nitrene (1.26 g, 8.00 mmol) was slowly added dropwise into the system. After the dropwise addition was completed, the system was stirred at room temperature for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and flash column chromatography (petroleum ether: acetone = 3: 1) was used to obtain the crude product. The crude product was dissolved in a small amount of dichloromethane, and was then poured into a large amount of diethyl ether to recrystallize. The product was obtained by filtration, and was a yellow solid (0.7 g, 61%, dr = 2: 1).

[0163] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 8.39 (d, J = 9.0 Hz, 2H, major isomer), 7.98 (d, J = 9.0 Hz, 2H, major isomer), 7.66 (d, J = 8.2 Hz, 2H, major isomer), 7.37 (d, J = 8.2 Hz, 2H, major isomer), 3.72 (s, 6H, major isomer), 2.44 (s, 3H, major isomer), 8.35 (d, J = 9.2 Hz, 2H, minor isomer), 8.03 (d, J = 8.2 Hz, 2H, minor isomer), 7.76 (d, J = 8.1 Hz, 2H, minor isomer), 7.35 (d, J = 8.0 Hz, 2H, minor isomer), 3.74 (s, 6H, minor isomer), 3.72 (s, 6H, minor isomer), 2.43 (s, 3H, minor isomer); 19 F NMR δ (376 MHz, CDC13, 293 K, TMS) δ -55.2 ppm (d, J = 128.2 Hz, major isomer), -63.2 (d, J = 128.3 Hz, major isomer), δ -59.75 ppm (d, J = 126.0 Hz, minor isomer), -60.52 ppm (d, J = 126.5 Hz, minor isomer); 13 CNMR (126 MHz, CDC13, 293 K, TMS) δ 165.92, 165.87, 165.51, 165.34, 150.22, 150.12, 145.17, 144.89, 133.60, 133.50, 131.81 (t, J = 371.7 Hz), 131.26, 131.18, 130.88, 130.60, 130.52, 129.75, 125.02, 124.98, 122.60, 122.31, 57.02, 55.05, 54.98, 52.05, 51.99, 21.70. IR (KBr): vmax = 3105, 1735, 1530, 1434, 1310, 1084, 761 cm -1 MS (ESI): 610.1 (M + + Na). HRMS (ESI): calcd for C 24 H 23 O 10 NF2NaS2: 610.0624 (M + + Na), found: 610.0623.

[0164] Example 5 Synthesis of nitro-substituted dithioazomethine reagent

[0165]

[0166] In a dry 500 mL Schlenk flask with a stir bar, 1,2-bis(4-nitrophenyl)disulfane (9.30 g, 30.0 mmol), PDFA (15.0 g, 42.0 mmol), 240 mL 1,4-dioxane were added and stirred at 60 °C in an oil bath for 12 h. After the reaction was completed, the mixture was cooled to room temperature, diluted with 200 mL water, extracted with ethyl acetate (200 mL x 3), the organic phase was combined, washed with 20 mL water, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash column chromatography (petroleum ether: ethyl acetate = 20: 1) to give a yellow solid 10.4 g in 97% yield.

[0167] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 8.25 (d, J = 8.4 Hz, 4H), 7.76 (d, J = 8.3 Hz, 4H); 19 F NMR (376 MHz, CDC13, 293 K, TMS) δ -47.37 ppm (s, 2F); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 148.99, 136.01, 135.04, 131.66 (t, J = 317.5 Hz), 124.31. IR (KBr): v max = 3101, 1605, 1547, 1437, 1348, 1045, 849, 741 cm -1 LRMS (DART): 359.0 (M + + H). HRMS (DART): calcd for C 13 H9O4N2F2S2: 359.9966 (M + + H), found: 358.9967.

[0168]

[0169] Rhodium(II) octanoate dimer (78.0 mg, 0.100 mmol) was weighed into a 250 mL Schlenk flask with stirring, and was purged with argon three times. Under argon protection, difluorobis((4-nitrophenyl)thio)methane (3.58 g, 10.0 mmol) was dissolved in super dry dichloromethane (100 mL), and then the azide (6.32 g, 40.0 mmol) was slowly added dropwise into the system. After the dropwise addition was completed, the system was stirred at room temperature for 12 h. After the reaction was completed, the solvent was removed by rotary evaporation, and flash column chromatography (petroleum ether: acetone = 3:1) was used to obtain the crude product. The crude product was dissolved in a small amount of dichloromethane, and was then poured into a large amount of diethyl ether for recrystallization. The product was obtained by filtration as a yellow solid (3.0 g, 48%).

[0170] 1 H NMR (500 MHz, CDC13, 293 K, TMS) δ 8.39 (d, J = 9.1 Hz, 4H, major isomer), 7.95 (d, J = 8.6 Hz, 4H, major isomer), 3.70 (s, 12H, major isomer), δ 8.37 (d, J = 8.7, 4H, minor isomer), 8.02 (d, J = 8.7 Hz, 4H, minor isomer), 3.74 (s, 12H, minor isomer). 19 F NMR (376 MHz, CDC13, 293 K, TMS) δ -53.66 ppm (d, J = 127.3 Hz, IF, major isomer), -61.31 (d, J = 127.2 Hz, IF, major isomer), -57.95 ppm (s, 2F, minor isomer); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 165.46, 165.28, 150.39, 150.26, 132.91, 132.81, 132.11 (t, J = 376.7 Hz) 130.87, 130.37, 125.19, 125.16, 55.81, 55.27, 52.24. IR (KBr): v max = 3105, 2953, 1737, 1530, 1435, 1346, 1088, 853, 769 cm -1 ; LRMS (ESI): 641.0 (M + + Na). HRMS (ESI): calculated for C 23 H 20 O 12 N2F2NaS2: 641.0318 (M +Found: 641.0330.

[0171] Application Example 1 Application of the bis-sulfur ylide difluoromethylene reagent 1 - photocatalytic gem-difluorocyclopropanation of olefins

[0172] General procedure: Ir(ppy)3(0.002 mmol), bis-sulfur ylide difluoromethylene reagent (0.8 mmol) were weighed into a 25 mL Schlenk tube, which was purged with argon three times. The olefin substrate (0.4 mmol) and super-dry toluene (4 mL) were added under argon protection. The system was placed under LED blue light irradiation and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was obtained by flash column chromatography.

[0173] The conditions were explored as follows:

[0174] Reaction conditions: in a solvent (1 mL), 4-vinylbiphenyl (0.1 mmol), ylide reagent (x equivalents) and catalyst (y mol%) were reacted under blue LED irradiation for t h; the yield was determined by 19 The yield was determined by1F NMR (1-fluoronaphthalene as internal standard).

[0175]

[0176] As shown in the formula below, no product was generated under dark conditions, and blue light was used to excite the photocatalyst Ir(ppy)3to the excited state, thereby completing the photocatalytic cycle.

[0177]

[0178] Next, we investigated the reaction substrates. The reaction is suitable for single- or multi-substituted styrene substrates, and is compatible with both electron-donating and electron-withdrawing substituents on the aromatic ring. In addition, we successfully applied the reaction to the derivatization of estrone molecules (application examples a1-a10).

[0179] Application Example 2 Application of the bis-sulfur ylide difluoromethylene reagent 2 - photocatalytic difluoromethylation of alcohols

[0180] General procedure: Ir(ppy)3(0.0004 mmol), bis-sulfur ylide difluoromethylene reagent (0.6 mmol) were weighed into a 25 mL Schlenk tube, which was purged with argon three times. The alcohol (0.4 mmol), deionized water (0.8 mmol) and super-dry toluene (4 mL) were added under argon protection. The system was placed under LED blue light at room temperature and stirred for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and the product was obtained by flash column chromatography.

[0181] The conditions were explored as follows:

[0182] Reaction conditions: in solvent (1 mL), phenethyl alcohol (0.1 mmol), ylide reagent (y equiv), and fac-Ir(ppy)3(z mol%) and water (x equiv) under blue LED irradiation for t h; yield determined by 19 The yield was determined by1F NMR (1-fluoronaphthalene as internal standard).

[0183]

[0184] Next we extended the reaction substrates. The reaction was suitable for primary or secondary alcohols, and was well compatible with functional groups such as methoxy, halogen, cyano, ester, and so on, and the heterocyclic substrate such as thiophene could also give the corresponding product in good yield (application examples b1-b10).

[0185] Application example a1

[0186]

[0187] Procedure: Ir(ppy)3(0.002 mmol), dithio ylide difluoromethylene reagent (0.8 mmol), olefin substrate (0.4 mmol) were weighed into a 25 mL Schlenk tube, and the system was purged with argon three times. Under argon protection, super-dry toluene (4 mL) was added, and the system was placed under LED blue light irradiation and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and white solid (74 mg, 80%, >95% NMR purity) was obtained by flash column chromatography.

[0188] Mp: 66-68 °C. 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.62 (t, J = 8.2 Hz, 4H), 7.49 (t, J = 7.6 Hz, 2H), 7.40 (t, J = 7.3 Hz, 1H), 7.34 (d, J = 8.1 Hz, 2H), 2.87-2.79 (m, 1H), 1.93-1.84 (m, 1H), 1.74-1.66 (m, 1H); 19 F NMR (376 MHz, CDC13) δ -125.71 (dtd, J = 153.8, 12.9, 3.9 Hz, IF), -142.18 (ddd, J = 153.8, 12.7, 4.9 Hz, IF); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 140.57, 140.07, 132.70, 128.77, 128.38, 127.32, 127.15, 127.00, 112.60 (dd, J = 287.1, 283.9 Hz), 26.91 (t, J = 11.7 Hz), 17.09 (t, J = 10.3 Hz) ppm. IR (KBr): v max = 3080, 3031, 1467, 1245, 1190, 1048, 937, 839, 764, 731, 687, 496 cm -1 MS (EI): 230 (100), 230. HRMS (EI): calcd for C 15 H 12 F2: 230.0902, found: 230.0903.

[0189] Application Example a2

[0190]

[0191] Procedure: Ir(ppy)3(0.002 mmol), dithio ylide difluoromethylene reagent (0.8 mmol) were weighed in a 25 mL Schlenk tube, and purged with argon for three times. Under argon protection, the olefin substrate (0.4 mmol) and super dry toluene (4 mL) were added, and the system was placed under LED blue light irradiation and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a brown transparent liquid (52 mg, 66%, NMR purity >95%).

[0192] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.13 (d, J = 8.7 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H), 2.96 (s, 6H), 2.74-2.66 (m, 1H), 1.80-1.71 (m, 1H), 1.55 (dtd, J = 11.8, 7.9, 3.8 Hz, 1H); 19 F NMR (376 MHz, CDC13) δ -126.20 (dtd, J = 152.6, 13.2, 3.8 Hz, 1F), -142.37 (ddd, J = 152.5, 12.7, 4.7 Hz, 1F); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 148.52, 127.81, 120.53, 111.99 (dd, J = 286.8, 283.9 Hz), 111.74, 39.72, 25.41 (t, J = 11.6 Hz), 15.71 (t, J = 10.5 Hz) ppm. IR (KBr): v max = 2889, 1619, 1529, 1470, 1361, 1236, 1200, 1048, 931, 818, 735, 516 cm -1 MS (EI): 196 (100), 197. HRMS (EI): calcd for C 11 H 13 NF2: 197.1011, found: 197.1009.

[0193] Application Example a3

[0194]

[0195] Procedure: Ir(ppy)3(0.002 mmol), dithioazomethine difluoromethylene reagent (0.8 mmol), olefin substrate (0.4 mmol) were weighed into a 25 mL Schlenk tube, which was purged with argon three times. Under argon protection, super dry toluene (4 mL) was added, and the system was placed under LED blue light irradiation and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and white solid (51 mg, 41%, >95% NMR purity) was obtained by flash column chromatography.

[0196] Mp: 108-110 °C. 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.83 (dd, J = 5.4, 3.1 Hz, 2H), 7.70 (dd, J = 5.4, 3.0 Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 4.83 (s, 2H), 2.70 (td, J = 12.4, 8.2 Hz, 1H), 1.79 (tdd, J = 12.4, 7.9, 4.9 Hz, 1H), 1.58 (dtd, J = 12.1, 8.0, 3.9 Hz, 1H); 19 F NMR (376 MHz, CDC13) δ -125.90 (dtt, J = 154.0, 12.9, 3.8 Hz, 1F), -142.30 (ddd, J = 154.0, 12.7, 4.7 Hz, 1F); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 167.96, 135.28, 133.97, 133.30, 132.01, 128.76, 128.29, 123.30, 112.42 (dd, J = 286.6, 284.4 Hz), 41.15, 26.83 (t, J = 11.4 Hz), 17.02 (t, J = 10.3 Hz) ppm. IR (KBr): v max = 3109, 1770, 1708, 1467, 1400, 1295, 1227, 1032, 940, 733, 532 cm -1 MS (EI): 160 (100), 313. HRMS (EI): calcd for C 18 H 13 O2NF2: 313.0909, found: 313.0915.

[0197] Application Example a4

[0198]

[0199] Procedure: Ir(ppy)3(0.002 mmol), dithioazomethine difluoromethylene reagent (0.8 mmol) were weighed in a 25 mL Schlenk tube, and purged with argon for three times. Under argon protection, the olefin substrate (0.4 mmol) and super dry toluene (4 mL) were added, and the system was placed under LED blue light irradiation and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (89 mg, 92%, NMR purity > 95%).

[0200] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.50 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.7 Hz, 2H), 3.80 (s, 3H), 2.09 - 2.01 (m, 4H), 1.91 (ddd, J = 15.0, 9.8, 5.2 Hz, 1H); 19 F NMR (376 MHz, CDC13) δ -133.54 (ddd, J = 160.5, 13.3, 5.2 Hz, 1F), -139.30 (ddd, J = 160.5, 15.0, 6.6 Hz, 1F); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 169.46, 160.06, 131.23, 124.58, 113.70, 110.29 (t, J = 291.6 Hz), 61.56 (dd, J = 12.7, 9.5 Hz), 55.18, 23.03 (t, J = 10.1 Hz), 20.72 ppm. IR (KBr): v max = 2939, 1766, 1519, 1466, 1232, 1134, 1024, 896, 837, 549 cm -1 MS (EI): 242. HRMS (EI): calculated for C 12 H 12 O3F2: 242.0749, found: 242.0751.

[0201] Application Example a5

[0202]

[0203] Procedure: Ir(ppy)3(0.002 mmol), dithioazomethine difluoromethylene reagent (0.8 mmol) were weighed in a 25 mL Schlenk tube, and purged with argon three times. Under argon protection, the olefin substrate (0.4 mmol) and super dry toluene (4 mL) were added, and the system was placed under LED blue light irradiation and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (99 mg, 85%, NMR purity > 95%).

[0204] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.51 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 2.11 - 2.04 (m, 4H), 1.94 (ddd, J = 15.4, 10.0, 5.6 Hz, 1H); 19 F NMR (376 MHz, CDC13) δ -133.91 (ddd, J = 161.8, 13.5, 5.5 Hz, 1F), -139.04 (ddd, J = 161.9, 14.6, 6.6 Hz, 1F); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 169.46, 160.06, 131.23, 124.58, 113.70, 110.29 (t, J = 291.6 Hz), 61.56 (dd, J = 12.7, 9.5 Hz), 55.18, 23.03 (t, J = 10.1 Hz), 20.72 ppm. IR (KBr): v max= 3108, 2925, 1774, 1758, 1459, 1370, 1231, 1210, 1145, 991, 836, 769, 549 cm -1 MS (EI): 178 (100), 193. HRMS (EI): calculated for C 11 H9NF2: 193.0698, found: 193.0697.

[0205] Application Example a6

[0206]

[0207] Operation steps: Ir(ppy)3(0.002 mmol), dithioazomethine difluoromethylene reagent (0.8 mmol) were weighed in a 25 mL Schlenk tube, and argon was exchanged three times. Under the protection of argon, olefin substrate (0.4 mmol) and super dry toluene (4 mL) were added, and the system was placed under LED blue light irradiation. Stirring at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (60 mg, 78%, nuclear magnetic purity > 95%).

[0208] 1 H NMR (400 MHz, CDCl3, 293 K, TMS) δ 7.63 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.3 Hz, 2H), 1.70 (ddd, J = 13.7, 7.8, 3.6 Hz, 1H), 1.53-1.46 (m, 4H); 19 F NMR (471 MHz, CDCl3) δ -132.24 (d, J = 151.8 Hz, 1F), -137.29 (d, J = 151.8 Hz, 1F); 13 C NMR (126 MHz, CDCl3, 293 K, TMS) δ 144.31, 132.36, 129.19, 118.56, 113.66 (dd, J = 290.5, 287.1 Hz), 111.16, 30.95 (t, J = 10.2 Hz), 22.65 (t, J = 9.9 Hz), 20.75 (d, J = 5.4 Hz) ppm. IR (KBr): v max = 2985, 2230, 1610, 1509, 1472, 1216, 1005, 906, 841, 741, 580 cm -1 MS (EI): 178 (100), 193. HRMS (EI): calculated for C 11 H9NF2: 193.0698, found: 193.0697.

[0209] Application Example a7

[0210]

[0211] Procedure: Ir(ppy)3(0.002 mmol), dithioazomethine difluoromethylene reagent (0.8 mmol) were weighed in a 25 mL Schlenk tube, and purged with argon for three times. Under argon protection, the olefin substrate (0.4 mmol) and super dry toluene (4 mL) were added, and the system was placed under LED blue light irradiation. The reaction was stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and column chromatography was performed to obtain a light yellow transparent liquid (42 mg, 47%, NMR purity >95%).

[0212] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.96 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 8.3 Hz, 2H), 3.89 (s, 3H), 2.30 (dd, J = 13.4, 7.6 Hz, 1H), 1.93 - 1.83 (m, 1H), 1.34 (dd, J = 6.2, 1.2 Hz, 3H); 19 F NMR (376 MHz, CDC13) δ -136.97 (dd, J = 153.5, 13.5 Hz, 1F), -138.12 (ddd, J = 153.6, 14.4, 1.8 Hz, 1F); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 166.77, 139.66, 129.64, 128.67, 127.66, 114.36 (dd, J = 291.5, 289.6 Hz), 52.06, 34.08 (t, J = 11.0 Hz), 24.97 (t, J = 9.8 Hz), 11.36 (d, J = 4.9 Hz) ppm. IR (KBr): v max = 2953, 1724, 1612, 1477, 1437, 1281, 1186, 1111, 1024, 987, 868, 711 cm -1 MS (EI): 195 (100), 226. HRMS (EI): calcd for C 12 H 12 O2F2: 226.0800, found: 226.0803.

[0213] Application Example a8

[0214]

[0215] Procedure: Ir(ppy)3(0.002 mmol), dithio-ylid dmfline reagent (0.8 mmol), olefin substrate (0.4 mmol) were weighed into a 25 mL Schlenk tube, and the system was purged with argon three times. Under argon protection, super-dry toluene (4 mL) was added, and the system was placed under LED blue light irradiation and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (67 mg, 71%, nuclear magnetic purity > 95%).

[0216] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.39-7.37 (m, 1H), 7.24-7.22 (m, 2H), 7.15-7.13 (m, 1H), 2.91-2.87 (m, 1H), 2.67-2.58 (m, 1H), 2.23-2.03 (m, 6H); 19 F NMR (376 MHz, CDC13) δ -129.84 (dd, J = 159.6, 16.6 Hz, IF), -142.42 (d, J = 159.5 Hz, IF); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 169.62, 135.46, 128.72, 128.37, 127.76, 126.52, 125.51, 111.68 (dd, J = 301.2, 299.1 Hz), 59.34 (dd, J = 15.3, 10.5 Hz), 30.35 (dd, J = 10.8, 8.2 Hz), 26.27 (d, J = 5.2 Hz), 20.88, 15.33 ppm. IR (KBr): v max = 2945, 1770, 1471, 1371, 1212, 1150, 1022, 917, 792, 551 cm -1 MS (EI): 168 (100), 238. HRMS (EI): calcd for C 13 H 12 O2F2: 238.0800, found: 238.0801.

[0217] Application Example a9

[0218]

[0219] Procedure: Ir(ppy)3(0.002 mmol), dithiole ylide difluoromethylene reagent (0.8 mmol) were weighed into a 25 mL Schlenk tube, which was purged with argon for three times. Under argon protection, the olefin substrate (0.4 mmol) and super dry toluene (4 mL) were added, and the system was placed under LED blue light irradiation and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (80 mg, 88%, NMR purity > 95%).

[0220] 1 H NMR (400 MHz, CDCl3, 293 K, TMS) δ 7.14 (d, J = 8.1 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 3.80 (s, 3H), 1.38-1.37 (m, 3H), 1.30 (d, J = 2.4 Hz, 3H), 0.91 (s, 3H); 19 F NMR (376 MHz, CDCl3) δ -140.69 (d, J = 146.3 Hz, 1F), -143.58 (d, J = 147.0 Hz, 1F); 13 C NMR (126 MHz, CDCl3, 293 K, TMS) δ 158.16, 131.54, 130.36, 117.53 (dd, J = 299.5, 294.3 Hz), 113.74, 55.14, 33.54 (t, J = 10.1 Hz), 27.38 (t, J = 9.7 Hz), 18.22-18.18 (m), 14.96 (d, J = 5.7 Hz) ppm. IR (KBr): v max = 2958, 1612, 1516, 1296, 1248, 1155, 1099, 1035, 989, 833, 607, 560 cm -1 MS (EI): 211 (100), 226. HRMS (EI): calcd for C 13 H 16 OF2: 226.1164, found: 226.1159.

[0221] Application Example a10

[0222]

[0223] Procedure: Ir(ppy)3(0.002 mmol), dithioazomethine difluoromethylene reagent (0.8 mmol), olefin substrate (0.4 mmol) were weighed in a 25 mL Schlenk tube, and the system was purged with argon three times. Under argon protection, super-dry toluene (4 mL) was added, and the system was placed under LED blue light irradiation and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and white solid (98 mg, 74%, >95% NMR purity) was obtained by flash column chromatography.

[0224] Mp: 107-109 °C. 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.25 (d, J = 8.0 Hz, 1H), 7.01 (d, J = 8.2 Hz, 1H), 6.97 (s, 1H), 2.91 (dd, J = 8.7, 3.8 Hz, 2H), 2.69 (td, J = 12.5, 8.3 Hz, 1H), 2.50 (dd, J = 18.8, 8.7 Hz, 1H), 2.44-2.40 (m, 1H), 2.28 (dd, J = 13.6, 6.9 Hz, 1H), 2.19-1.95 (m, 4H), 1.78 (tdd, J = 12.3, 7.8, 4.8 Hz, 1H), 1.68-1.38 (m, 7H), 0.90 (s, 3H); 19 F NMR (376 MHz, CDC13) δ -125.94 (dtt, J = 153.4, 13.1, 3.9 Hz, IF), -142.30 (ddd, J = 153.4, 12.7, 4.8 Hz, IF); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 220.79, 138.70, 136.59, 130.97, 128.59, 125.46, 125.29, 112.62 (t, J = 287.0 Hz), 50.38, 47.90, 44.20, 38.00, 35.78, 31.49, 29.28, 26.71 (t, J = 11.4 Hz), 26.37, 25.60, 21.51, 16.79 (td, J = 10.5, 3.6 Hz), 13.76 ppm. IR (KBr): v max = 2943, 1739, 1504, 1470, 1375, 1245, 1209, 1046, 841, 824 cm -1 MS (EI): 330. HRMS (EI): calcd for C 21 H 24 OF2: 330.1790, found: 330.1784.

[0225] Application Example b1

[0226]

[0227] Operation steps: Ir(ppy)3(0.0004 mmol), bisthioylide difluoromethylene reagent (0.6 mmol) were weighed in a 25 mL Schlenk tube, and argon was exchanged three times. Under the protection of argon, alcohol (0.4 mmol), deionized water (0.8 mmol) and super dry toluene (4 mL) were added, and the system was placed under LED blue light for stirring reaction at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (51 mg, 74%, nuclear magnetic purity > 95%).

[0228] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.33-7.30 (m, 2H), 7.26-7.22 (m, 3H), 6.18 (t, J = 74.8 Hz, 1H), 4.06 (t, J = 7.1 Hz, 2H), 2.96 (t, J = 7.1 Hz, 2H); 19 F NMR (376 MHz, CDC13) δ -84.20 (d, J = 74.8 Hz, 2F); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 137.49, 128.92, 128.57, 126.71, 116.03 (t, J = 260.8 Hz), 64.02 (t, J = 5.6 Hz), 35.72 ppm. IR (KBr): v max = 2964, 1498, 1456, 1363, 1190, 1016, 750, 700, 492 cm -1 MS (EI): 172 (100), 172. HRMS (EI): calcd for C9H 10 OF2: 172.0694, found: 172.0698.

[0229] Application Example b2

[0230]

[0231] Procedure: Ir(ppy)3(0.0004 mmol), dithio-ylid dimesylate reagent (0.6 mmol) were weighed into a 25 mL Schlenk tube, which was purged with argon three times. Under argon protection, alcohol (0.4 mmol), deionized water (0.8 mmol) and super dry toluene (4 mL) were added. The system was placed under LED blue light and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (65 mg, 80%, NMR purity > 95%).

[0232] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.16 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.5 Hz, 2H), 6.19 (t, J = 74.9 Hz, 1H), 4.03 (t, J = 7.1 Hz, 2H), 3.80 (s, 3H), 2.91 (t, J = 7.1 Hz, 2H); 19 F NMR (376 MHz, CDC13) δ -84.08 (d, J = 74.9 Hz, 2F); 13 C NMR (151 MHz, CDC13, 293 K, TMS) δ 158.37, 129.83, 129.43, 116.02 (t, J = 260.2 Hz), 113.93, 64.27 (t, J = 5.0 Hz), 55.20, 34.80 ppm. IR (KBr): v max = 2962, 1614, 1515, 1302, 1250, 1179, 1035, 830 cm -1 MS (EI): 121 (100), 202. HRMS (EI): calcd for C 10 H 12 O2F2: 202.0800, found: 202.0795.

[0233] Application Example b3

[0234]

[0235] Procedure: Ir(ppy)3(0.0004 mmol), dithio-ylid dimesylate reagent (0.6 mmol) were weighed into a 25 mL Schlenk tube, which was purged with argon three times. Under argon protection, alcohol (0.4 mmol), deionized water (0.8 mmol) and super dry toluene (4 mL) were added. The system was placed under LED blue light and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (65 mg, 80%, NMR purity > 95%).

[0236] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.15 (dd, J = 8.3, 5.6 Hz, 2H), 6.99 (t, J = 8.7 Hz, 2H), 6.22 (t, J = 75.0 Hz, 1H), 3.85 (t, J = 6.3 Hz, 2H), 2.71 (t, J = 7.6 Hz, 2H), 1.98 - 1.91 (m, J = 13.7, 2H); 19 F NMR (376 MHz, CDC13) δ -83.92 (d, J = 75.0 Hz, 2F), -117.47 - -117.54 (m, 1F); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 161.40 (d, J = 243.9 Hz), 136.72 (d, J = 3.3 Hz), 129.84 (d, J = 7.8 Hz), 116.15 (t, J = 259.6 Hz), 115.21 (d, J = 21.2 Hz), 62.52 (t, J = 5.5 Hz), 30.95 (d, J = 19.5 Hz) ppm. IR (KBr): v max = 2968, 1490, 1403, 1363, 1189, 1135, 1074, 1012, 808, 512 cm -1 MS (EI): 204. HRMS (EI): calcd for C 10 H 11 OF3: 204.0757, found: 204.0760.

[0237] Application Example b4

[0238]

[0239] Procedure: Ir(ppy)3(0.0004 mmol), dithio ylide difluoromethylene reagent (0.6 mmol) were weighed in a 25 mL Schlenk tube, which was purged with argon three times. Under argon protection, alcohol (0.4 mmol), deionized water (0.8 mmol) and ultradry toluene (4 mL) were added, and the system was placed under LED blue light and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (84 mg, 84%, NMR purity >95%).

[0240] 1H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.44 (d, J = 8.3 Hz, 2H), 7.11 (d, J = 8.3 Hz, 2H), 6.18 (t, J = 74.6 Hz, 1H), 4.05 (t, J = 6.9 Hz, 2H), 2.91 (t, J = 6.9 Hz, 2H); 19 F NMR (376 MHz, CDC13) δ -84.33 (d, J = 74.6 Hz, 2F); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 136.51, 131.56, 130.60, 120.52, 115.86 (t, J = 261.4 Hz), 63.44 (t, J = 5.6 Hz), 35.01 ppm. IR (KBr): v max = 2967, 1602, 1511, 1159, 1132, 1016, 822, 755, 531 cm -1 MS (EI): 250. HRMS (EI): calcd for C9H9OBrF2: 249.9799, found: 249.9806.

[0241] Application Example b5

[0242]

[0243] Procedure: Ir(ppy)3(0.0004 mmol), dithioazomethine difluoromethylene reagent (0.6 mmol) were weighed in a 25 mL Schlenk tube, and the system was purged with argon three times. Under argon protection, alcohol (0.4 mmol), deionized water (0.8 mmol), and ultradry toluene (4 mL) were added, and the system was stirred at room temperature under LED blue light for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and flash column chromatography was performed to obtain a light yellow transparent liquid (45 mg, 49%, nuclear magnetic purity >95%).

[0244] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.45 (d, J = 8.6 Hz, 2H), 7.19 (dd, J = 8.2, 1.7 Hz, 1H), 6.32 (t, J = 73.7 Hz, 1H), 4.85 (s, 2H); 19 F NMR (376 MHz, CDC13) δ -84.61 (d, J = 73.6 Hz, 2F); 13C NMR (126 MHz, CDC13, 293 K, TMS) δ 135.65, 132.74, 132.41, 130.58, 129.60, 126.87, 115.63 (t, J = 262.3 Hz), 63.50 (t, J = 6.3 Hz) ppm. IR (KBr): v max = 2963, 1567, 1471, 1440, 1359, 1211, 1185, 1135, 1086, 1016, 750 cm -1 MS (EI): 226. HRMS (EI): calcd for C8H6OCl2F2: 225.9758, found: 225.9757.

[0245] Application Example b6

[0246]

[0247] Procedure: Ir(ppy)3(0.0004 mmol), dithioazomethine difluoromethylene reagent (0.6 mmol) were weighed in a 25 mL Schlenk tube, and purged with argon three times. Under argon protection, alcohol (0.4 mmol), deionized water (0.8 mmol) and super dry toluene (4 mL) were added, and the system was placed under LED blue light at room temperature and stirred for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (52 mg, 46%, NMR purity >95%).

[0248] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.86 (d, J = 7.9 Hz, 1H), 7.45 (d, J = 7.4 Hz, 1H), 7.38 (t, J = 7.5 Hz, 1H), 7.04 (t, J = 7.6 Hz, 1H), 6.38 (t, J = 74.2 Hz, 1H), 4.92 (s, 2H); 19 F NMR (376 MHz, CDC13) δ -84.32 (d, J = 74.1 Hz, 2F); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 139.41, 137.87, 129.90, 128.88, 128.49, 115.97 (t, J = 261.9 Hz), 97.44, 69.19 (t, J = 5.8 Hz) ppm. IR (KBr): v max = 2963, 1475, 1385, 1354, 1186, 1133, 1089, 1033, 818, 687 cm -1MS (El): 284. HRMS (El): calculated for C8H7OF2I: 283.9504, found: 283.9511.

[0249] Application Example b7

[0250]

[0251] Procedure: Ir(ppy)3(0.0004 mmol), dithioazomethine difluoromethylene reagent (0.6 mmol) were weighed in a 25 mL Schlenk tube, which was purged with argon three times. Under argon protection, alcohol (0.4 mmol), deionized water (0.8 mmol) and ultradry toluene (4 mL) were added, and the system was placed under LED blue light for stirring reaction at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (47 mg, 59%, NMR purity >95%).

[0252] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.60 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 6.18 (t, J = 74.2 Hz, 1H), 4.09 (t, J = 6.6 Hz, 2H), 3.01 (t, J = 6.6 Hz, 2H); 19 F NMR (376 MHz, CDC13) δ -84.68 (d, J = 74.2 Hz, 2F); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 143.25, 132.27, 129.69, 118.81, 115.70 (t, J = 262.1 Hz), 110.63, 62.73 (t, J = 5.7 Hz), 35.61 ppm. IR (KBr): v max = 2970, 2229, 1610, 1507, 1364, 1185, 1131, 1086, 1015, 841, 570 cm -1 MS (El): 284. HRMS (El): calculated for C8H7OF2I: 283.9504, found: 283.9511. 10 H9ONF2: 197.0647, found: 197.0648.

[0253] Application Example b8

[0254]

[0255] Procedure: Ir(ppy)3(0.0004 mmol), dithio-ylid dimesylate reagent (0.6 mmol) were weighed into a 25 mL Schlenk tube, which was purged with argon three times. Under argon protection, alcohol (0.4 mmol), deionized water (0.8 mmol) and super dry toluene (4 mL) were added. The system was placed under LED blue light and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (60 mg, 85%, NMR purity > 95%).

[0256] 1 H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.29 (dd, J = 4.8, 3.0 Hz, 1H), 7.07-7.06 (m, 1H), 7.00 (d, J = 4.9 Hz, 1H), 6.22 (t, J = 74.7 Hz, 1H), 4.08 (t, J = 6.9 Hz, 2H), 3.01 (t, J = 6.9 Hz, 2H); 19 F NMR (376 MHz, CDC13) δ -84.20 (d, J = 74.8 Hz, 2F); 13 C NMR (151 MHz, CDC13, 293 K, TMS) δ 137.70, 128.15, 125.65, 121.65, 116.00 (t, J = 260.5 Hz), 63.36 (t, J = 5.3 Hz), 30.14 ppm. IR (KBr): v max = 2967, 1402, 1362, 1189, 1135, 1085, 1012, 777, 634 cm -1 MS (EI): 178. HRMS (EI): calcd for C7H8OF2S: 178.0258, found: 178.0255.

[0257] Application Example b9

[0258]

[0259] Procedure: Ir(ppy)3(0.0004 mmol), dithio-ylid dimesylate reagent (0.6 mmol) were weighed into a 25 mL Schlenk tube, which was purged with argon three times. Under argon protection, alcohol (0.4 mmol), deionized water (0.8 mmol) and super dry toluene (4 mL) were added. The system was placed under LED blue light and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (60 mg, 85%, NMR purity > 95%).

[0260] 1H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.89 - 7.80 (m, 4H), 7.53 - 7.48 (m, 3H), 6.21 (dd, J = 77.9, 73.5 Hz, 1H), 5.35 (q, J = 6.5 Hz, 1H), 1.67 (d, J = 6.5 Hz, 3H); 19 F NMR (376 MHz, CDC13) δ -81.56 (dd, J = 163.5, 77.9 Hz, IF), -83.11 (dd, J = 163.5, 73.5 Hz, IF); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 138.60, 133.13, 133.10, 128.65, 127.98, 127.71, 126.39, 126.25, 124.95, 123.64, 116.26 (dd, J = 262.1, 255.8 Hz), 74.26 (t, J = 4.2 Hz), 23.66 ppm. IR (KBr): v max = 2985, 1509, 1455, 1379, 1201, 1130, 1071, 1020, 897, 820, 749 cm - 1 MS (EI): 207 (100), 222. HRMS (EI): calcd for C 13 H 12 OF2: 222.0851, found: 222.0857.

[0261] Application Example b10

[0262]

[0263] Procedure: Ir(ppy)3(0.0004 mmol), dithioazomethine difluoromethylene reagent (0.6 mmol) were weighed in a 25 mL Schlenk tube, and the system was replaced with argon three times. Under the protection of argon, alcohol (0.4 mmol), deionized water (0.8 mmol), and super dry toluene (4 mL) were added, and the system was stirred at room temperature under LED blue light for 3 h. After the reaction was completed, the solvent was removed by rotary evaporation, and fast column chromatography was used to obtain a colorless transparent liquid (57 mg, 51%, NMR purity > 95%).

[0264] 1H NMR (400 MHz, CDC13, 293 K, TMS) δ 7.96 (d, J = 8.3 Hz, 2H), 7.41 (d, J = 8.3 Hz, 2H), 6.24 (t, J = 74.9 Hz, 1H), 4.52 - 4.35 (m, 3H), 2.00 (q, J = 6.4 Hz, 2H), 1.36 (d, J = 6.2 Hz, 3H); 19 F NMR (376 MHz, CDC13) δ -80.67 - -81.87 (m, 2F); 13 C NMR (126 MHz, CDC13, 293 K, TMS) δ 165.55, 139.39, 130.89, 128.70, 128.53, 117.12 (t, J = 260.2 Hz), 68.85 (t, J = 4.3 Hz), 61.34, 35.74, 21.55 ppm. IR (KBr): v max = 2982, 1717, 1596, 1489, 1402, 1274, 1209, 1105, 1016, 851, 760, 686 cm -1 MS (EI): 278. HRMS (EI): calcd for C 12 H 13 O3ClF2: 278.0516, found: 278.0517.

[0265] HPLC (IB, 0.46 x 25 cm, 5 μm, n-hexane / isopropanol = 96 / 4 (v / v%), flow rate 0.7 mL / min, UV detection wavelength 214 nm), retention time = 6.87 min (minor) and 7.38 min (major).[α] D 25 = -21.3 (c 1.0, CHCl3, 93% ee).

Claims

1. A compound as shown in formula I: wherein m and n are independently 0, 1, 2, 3, 4 or 5; R 7 and R 8 are independently C1-C6alkyl, C1-C6alkoxy, nitro or halogen; E is CO2R 9 ; R 9 R is CrC6alkyl.

2. The compound of claim 1, having the formula I, wherein which meets one or more of the following conditions: (1) n and m are independently 0, 1 or 2; (2) R 7 and said R 8 are the same or different; (3) said R 7 and said R 8 wherein said halogen is independently F, Cl, Br, or I; (4) said R 7 and said R 8 independently -CH3, -OCH3, -NO2, or -Cl; (5) said R 9 is methyl.

3. The compound as shown in formula I according to claim 1, wherein, which meets one or two of the following conditions: (1) n and m are independently 0 or 1; (2) said R 7 and said R 8 wherein said halogen is independently Cl.

4. The compound of claim 2, having the formula I, wherein the compound as shown in formula I is any one of the following compounds, 5.A method for preparing a compound as shown in formula I, comprising the following steps: Step (1) is method 1 or method 2: Method 1: in an organic solvent, in the presence of (trifluoromethyl) trimethylsilane and a base, the compound as shown in formula II is subjected to the following reaction to obtain the compound as shown in formula III; Method 2: in an organic solvent, in the presence of (triphenylphosphonium) difluoroacetic acid inner salt, the compound as shown in formula II is subjected to the following reaction to obtain the compound as shown in formula III; Step (2): in an organic solvent, in the presence of a catalyst, the compound as shown in formula III and the compound as shown in formula IV are subjected to the following reaction to obtain the compound as shown in formula I; wherein R 7 , R 8 , m, n, E and R 9 are as defined in any one of claims 1 to 4.

6. The method of claim 5, wherein the compound of formula I is prepared by the process of: ###00010### I The preparation method meets one or more of the following conditions: (1) in method 1, the organic solvent is an amide solvent; (2) in method 1, the base is one or more of lithium tert-butoxide, potassium tert-butoxide and sodium tert-butoxide; (3) in method 1, the molar ratio of the base to the compound as shown in formula II is 1.5:1-5:1; (4) in method 1, the molar ratio of (trifluoromethyl) trimethylsilane to the compound as shown in formula II is 1.5:1-3:1; (5) in method 1, the molar concentration of the compound as shown in formula II in the organic solvent is 0.2-1.2 mol / L; (6) in method 1, the temperature of the reaction is 0-60℃; (7) in method 2, the organic solvent is an ether solvent; (8) in method 2, the molar ratio of (triphenylphosphonium) difluoroacetic acid inner salt to the compound as shown in formula II is 1.2:1-3:1; (9) in method 2, the molar concentration of the compound as shown in formula II in the organic solvent is 0.1-1.2 mol / L; (10) in method 2, the temperature of the reaction is 0-80℃; (11) in method 1 or method 2, the reaction is carried out under inert gas protection; (12) in step (2), the organic solvent is a halogenated hydrocarbon solvent and / or an aromatic solvent; (13) In step (2), the catalyst is one or more of Rh2(esp)2, Rh2(OAc)4, and Rh2(C7H 15 CO2)4. (14) in step (2), the molar ratio of the catalyst to the compound as shown in formula III is (0.5-2):100; (15) in step (2), the molar ratio of the compound as shown in formula IV to the compound as shown in formula III is 1.5:1-5:1; (16) in step (2), the molar concentration of the compound as shown in formula III in the organic solvent is 0.05-0.2 mol / L; (17) in step (2), the temperature of the reaction is 0-40℃; (18) In step (2), the reaction is carried out under inert gas protection; (19) In step (2), the compound of formula IV is slowly added dropwise into the solution of the compound of formula III and the organic solvent.

7. The process for the preparation of a compound of formula I according to claim 6, wherein The preparation method meets one or more of the following conditions: (1) In method 1, the amide solvent is N,N-dimethylformamide and / or N,N-dimethylacetamide; (2) In method 1, the base is lithium tert-butoxide; (3) In method 1, the molar ratio of the base to the compound of formula II is 2:1-4:1; (4) In method 1, the molar ratio of (trifluoromethyl)trimethylsilane to the compound of formula II is 1.5:1-2.5:1; (5) In method 1, the molar concentration of the compound of formula II in the organic solvent is 0.5-1 mol / L; (6) In method 1, the reaction temperature is 20-30°C; (7) In method 2, the ether solvent is dioxane; (8) In method 2, the molar ratio of (triphenylphosphoniumyl) difluoroacetic acid inner salt to the compound of formula II is 1.2:1-2.5:1; (9) In method 2, the molar concentration of the compound of formula II in the organic solvent is 0.1-1 mol / L; (10) In method 2, the reaction temperature is 55-65°C; (11) In method 1 or method 2, the reaction is carried out under nitrogen protection; (12) In step (2), the halogenated hydrocarbon solvent is selected from one or more of dichloromethane, chloroform and 1,2-dichloroethane; (13) In step (2), the aromatic solvent is selected from one or more of toluene, xylene, chlorobenzene and trifluorotoluene; (14) In step (2), the catalyst is Rh2(esp)2or Rh2(C7H 15 CO2)4; (15) In step (2), the molar ratio of the catalyst to the compound of formula III is (0.8-1.5):100; (16) In step (2), the molar ratio of the compound of formula IV to the compound of formula III is 2:1-4:1; (17) In step (2), the molar concentration of the compound of formula III in the organic solvent is 0.02-0.15 mol / L; (18) In step (2), the reaction temperature is 20-30°C; (19) In step (2), the reaction is carried out under argon protection.

8. The process for the preparation of a compound of formula I according to claim 7, wherein The preparation method meets one or more of the following conditions: (1) In method 1, the amide solvent is N,N-dimethylformamide; (2) In method 1, the molar ratio of the base to the compound of formula II is 3:1; (3) In method 1, the molar ratio of (trifluoromethyl)trimethylsilane to the compound of formula II is 2:1; (4) In method 1, the molar concentration of the compound of formula II in the organic solvent is 0.8 mol / L; (5) In method 2, the organic solvent is 1,4-dioxane; (6) In method 2, the molar ratio of the (triphenylphosphonium-based) difluoroacetic acid inner salt to the compound of formula II is 2:1 or 1.4:1; (7) In method 2, the molar concentration of the compound of formula II in the organic solvent is 0.125 mol / L; (8) In step (2), the organic solvent is dichloromethane and / or toluene; (9) In step (2), the molar ratio of the catalyst to the compound of formula III is 1:100; (10) In step (2), the molar ratio of the compound of formula IV to the compound of formula III is 3:1 or 4:1; (11) In step (2), the molar concentration of the compound of formula III in the organic solvent is 0.1 mol / L.

9. The method of claim 8, wherein the compound of formula I is prepared by the process of: ###00010### I The preparation method satisfies the following condition: in step (2), the organic solvent is dichloromethane.

10. The following compounds:

11. Use of the compound of formula I in any one of claims 1-4 in an organic synthesis reaction, wherein the organic synthesis reaction is a gem-difluorocyclopropanation reaction of an olefin or a difluoromethylation reaction of an alcohol.

12. The use according to claim 11, wherein the compound is ###00010### or a pharmaceutically acceptable salt thereof. The use satisfies one or more of the following conditions: (1) The gem-difluorocyclopropanation reaction of an olefin comprises the following steps: in an organic solvent, in the presence of a catalyst and the compound of formula I, under blue light irradiation, a compound containing a moiety of formula V undergoes a gem-difluorocyclopropanation reaction to obtain a compound containing a moiety of formula Va; (2) The difluoromethylation reaction of an alcohol comprises the following steps: in a solvent, in the presence of a catalyst and the compound of formula I, under blue light irradiation, a compound containing a moiety of formula VI undergoes a difluoromethylation reaction to obtain a compound containing a moiety of formula VIb; E, m, n, R 7 and R 8 are as defined in any one of claims 1 to 4.

13. The use according to claim 12, wherein the compound is ###00010### or a pharmaceutically acceptable salt thereof. The use satisfies one or more of the following conditions: (1) The gem-difluorocyclopropanation reaction of an olefin comprises the following steps: in an organic solvent, in the presence of a catalyst and the compound of formula I, under blue light irradiation, a compound of formula VII undergoes a gem-difluorocyclopropanation reaction of an olefin to obtain a compound of formula VIIa; wherein R 1 is R 3 is hydrogen or C1-C6alkyl; or R 3 and R 1 with the atom to which they are attached form a 9-18 membered aromatic ring; Ring A is a 6-20-membered aromatic ring; R 5 independently C1-C6alkyl, C1-C6alkyl substituted by one or more R 5-1 independently C1-C6alkyl, C1-C6alkyl substituted by one or more R b R c , halo, cyano, oxo, or thioxo; R 5-1 independently substituted with one or more R 5-1-1 substituted 5-10 membered heteroaryl, C1-C6alkoxy, -NR b R c , halogen or cyano; in said 5-10 membered heteroaryl, the heteroatoms are selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 5-1-1 independently oxo; R b and R c independently C1-C6alkyl; k is 0, 1, or 2; R 2 is hydrogen, C1-C6alkyl or -OC(O)-C1-C6alkyl; R 4 is hydrogen or C1-C6alkyl; (2) The difluoromethylation reaction of an alcohol comprises the following steps: in a solvent, in the presence of a catalyst and the compound of formula I, under blue light irradiation, a compound of formula VIII undergoes a difluoromethylation reaction to obtain a compound of formula VIIIb; wherein L is a C1-C6 alkylene group or a *-COOC1-C6 alkylene group, which is connected to ring B through the * end; Ring B is a 6-10-membered aromatic ring or a 5-10-membered heteroaromatic ring, wherein the 5-10-membered heteroaromatic ring contains 1, 2, or 3 heteroatoms selected from N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 6 independently C1-C6alkyl, C1-C6alkoxy, halogen, or cyano; t is 0, 1, 2, or 3; (3) In the gem-difluorocyclopropanation reaction of olefins, the catalyst is one or more of Ir(ppy)3, Ir(p- t Bu-ppy)3, Ru(bpy)3(PF6)2, and Rhodamine 6G. (4) In the gem-difluorocyclopropanation reaction of an olefin, the molar ratio of the catalyst to the compound of formula VII is (0.05-2):100; (5) the molar ratio of the compound of formula I to the compound of formula VII in the gem-difluorocyclopropanation reaction of olefins is (1-2.5): 1; (6) the organic solvent in the gem-difluorocyclopropanation reaction of olefins is one or more of nitrile solvents, ketone solvents, halogenated alkane solvents, ether solvents, and aromatic solvents; (7) the volume-molar ratio of the organic solvent to the compound of formula VII in the gem-difluorocyclopropanation reaction of olefins is 5 mL / mmol-20 mL / mmol; (8) the temperature of the gem-difluorocyclopropanation reaction of olefins is 10-40°C; (9) the wavelength of the blue light is 463-475 nm in the gem-difluorocyclopropanation reaction of olefins; (10) the catalyst in the difluoromethylation reaction of alcohols is fac-Ir(ppy)3; (11) the molar ratio of the catalyst to the compound of formula VIII in the difluoromethylation reaction of alcohols is (0.05-0.5):100; (12) the molar ratio of the compound of formula I to the compound of formula VIII in the difluoromethylation reaction of alcohols is (1-2):1; (13) the difluoromethylation reaction of alcohols is carried out in the presence of water, and the molar ratio of the water to the compound of formula VIII is (0-4):1; (14) the solvent in the difluoromethylation reaction of alcohols is one or more of nitrile solvents, halogenated alkane solvents, ether solvents, amide solvents, and aromatic solvents; (15) the volume-molar ratio of the solvent to the compound of formula VIII in the difluoromethylation reaction of alcohols is 5 mL / mmol-20 mL / mmol; (16) the temperature of the difluoromethylation reaction of alcohols is 10-40°C; (17) the wavelength of the blue light is 463-475 nm in the difluoromethylation reaction of alcohols.

14. The use according to claim 13, wherein the compound is ###00017### or a pharmaceutically acceptable salt thereof. The application meets one or more of the following conditions: (1) In the gem-difluorocyclopropanation reaction of olefins, the catalyst is Ir(ppy)3 and / or Ir(p- t Bu-ppy)3; (2) the molar ratio of the catalyst to the compound of formula VII in the gem-difluorocyclopropanation reaction of olefins is (0.5-2):100; (3) the molar ratio of the compound of formula I to the compound of formula VII in the gem-difluorocyclopropanation reaction of olefins is (1.5-2.5):1; (4) the organic solvent in the gem-difluorocyclopropanation reaction of olefins is an aromatic solvent; (5) the volume-molar ratio of the organic solvent to the compound of formula VII in the gem-difluorocyclopropanation reaction of olefins is 5-15 mL / mmol; (6) the temperature of the gem-difluorocyclopropanation reaction of olefins is 20-30°C; (7) The gem-difluorocyclopropanation reaction of the olefin, wherein the blue light is a blue light LED; (8) The difluoromethylation reaction of the alcohol, wherein the molar ratio of the catalyst to the compound of Formula VIII is (0.1-0.5):100; (9) The difluoromethylation reaction of the alcohol, wherein the molar ratio of the compound of Formula I to the compound of Formula VIII is (1.5-2):1; (10) The difluoromethylation reaction of the alcohol, wherein the difluoromethylation reaction is carried out in the presence of water, and the molar ratio of the water to the compound of Formula VIII is (1-4):1; (11) The difluoromethylation reaction of the alcohol, wherein the solvent is an aromatic solvent; (12) The difluoromethylation reaction of the alcohol, wherein the volume molar ratio of the solvent to the compound of Formula VIII is 5-15 mL / mmol; (13) The difluoromethylation reaction of the alcohol, wherein the temperature of the difluoromethylation reaction is 20-30 °C; (14) The difluoromethylation reaction of the alcohol, wherein the blue light is a blue light LED.

15. The use according to claim 13, wherein the compound is ###00017### or a pharmaceutically acceptable salt thereof. The application satisfies one or more of the following conditions: (1) The gem-difluorocyclopropanation reaction of the olefin, wherein the molar ratio of the catalyst to the compound of Formula VII is 0.05:100, 0.2:100, 0.5:100, 1:100, or 2:100; (2) The gem-difluorocyclopropanation reaction of the olefin, wherein the molar ratio of the compound of Formula I to the compound of Formula VII is 1:1, 1.5:1, 2:1, or 2.5:1; (3) The gem-difluorocyclopropanation reaction of the olefin, wherein the nitrile solvent is acetonitrile; (4) The gem-difluorocyclopropanation reaction of the olefin, wherein the ketone solvent is acetone; (5) The gem-difluorocyclopropanation reaction of the olefin, wherein the halogenated alkane solvent is dichloromethane; (6) The gem-difluorocyclopropanation reaction of the olefin, wherein the ether solvent is tetrahydrofuran; (7) The gem-difluorocyclopropanation reaction of the olefin, wherein the aromatic solvent is toluene; (8) The gem-difluorocyclopropanation reaction of the olefin, wherein the volume molar ratio of the organic solvent to the compound of Formula VII is 10 mL / mmol; (9) The difluoromethylation reaction of the alcohol, wherein the molar ratio of the catalyst to the compound of Formula VIII is 0.05:100, 0.1:100, 0.3:100, or 0.5:100; (10) The difluoromethylation reaction of the alcohol, wherein the molar ratio of the compound of Formula I to the compound of Formula VIII is 1:1, 1.5:1, or 2:1; (11) The difluoromethylation reaction of the alcohol, wherein the difluoromethylation reaction is carried out in the presence of water, and the molar ratio of the water to the compound of Formula VIII is 0.5:1, 1:1, 2:1, or 4:1; (12) In the difluoromethylation reaction of the alcohol, the nitrile solvent is acetonitrile; (13) In the difluoromethylation reaction of the alcohol, the halogenated alkane solvent is dichloromethane; (14) In the difluoromethylation reaction of the alcohol, the ether solvent is tetrahydrofuran; (15) In the difluoromethylation reaction of the alcohol, the amide solvent is N,N-dimethylformamide; (16) In the difluoromethylation reaction of the alcohol, the aromatic solvent is toluene; (17) In the difluoromethylation reaction of the alcohol, the volume molar ratio of the solvent to the compound as shown in formula VIII is 10 mL / mmol.

16. The use of claim 13, wherein, The application satisfies any one of the following conditions: (1) said ring A is a phenyl ring or (2) R 2 , R 3 , R 4 , R 5 , R b , and R c , the C1-C6 alkyl is independently C1-C4 alkyl; (3) R 5 and R 5-1 wherein said C1-C6alkoxy is independently C1-C4alkoxy; (4) R 5 and R 5-1 wherein said halogen is F, CI, Br or I; (5) R 5 In some embodiments, the 6-10 membered aryl group is phenyl. (6) when R 3 and R 1 together with the atoms to which they are attached form a 9-18 membered aromatic ring, the 9-18 membered aromatic ring is a 9-12 membered aromatic ring; (7) k is 0 or 1; (8) In L, the C1-C6 alkylene is C1-C4 alkylene; (9) In L, the *-COOC1-C6 alkylene is *-COOC1-C4 alkylene; (10) In ring B, the 6-18-membered aromatic ring is a 6-10-membered aromatic ring; (11) In ring B, the 5-10-membered heteroaromatic ring is a 5-6-membered heteroaromatic ring; (12) R 6 In some embodiments, the C1-C6alkyl is independently C1-C4alkyl. (13) R 6 In particular, the C1-C6alkoxy is independently C1-C4alkoxy. (14) R 6 In particular, the halogen is F, CI, Br or I. (15) t is 0, 1 or 2.

17. The use according to claim 16, wherein The application satisfies any one of the following conditions: (1) R 2 (2) R 3 (3) R 4 (4) R 5 (5) R b (6) R c (7) R (8) R (9) R (10) R (11) R (12) R (13) R (14) R (15) R (16) R (17) R (18) R (19) R (20) R (21) R (22) R (23) R (24) R (25) R (26) R (27) R (28) R (29) R (30) R (31) R (32) R (33) R ( (2) R 5 and R 5-1 wherein said C1-C6alkoxy is independently methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, or t-butoxy; (3) R 5 and R 5-1 wherein the halogen is Br; (4) when R 3 and R 1 together with the atoms to which they are attached form a 9-18 membered aromatic ring, said 9-18 membered aromatic ring is (5) In L, the C1-C6 alkylene is -CH2-, -CH2CH2-, -CH(CH3)-, -CH2CH2CH2-, -CH(CH3)CH2-, -C(CH3)2-, -CH2CH2CH2CH2-, -CH(CH3)CH2CH2-, -CH2CH(CH3)CH2- or -CH2C(CH3)2-; (6) In L, the *-COOC1-C6alkylene is *-COO-CH2-, * -COO-CH2CH2-, *-COO-CH(CH3)-, *-COO-CH2CH2CH2-, *-COO-CH(CH3)CH2-, *-COO-C(CH3)2-, *-COO-CH2CH2CH2CH2-, *-COO-CH(CH3)CH2CH2-, *-COO-CH2CH2CH(CH3)-, * -COO-CH2CH(CH3)CH2-, or *-COO-CH2C(CH3)2-. (7) In ring B, the 6-18-membered aromatic ring is a benzene ring or a naphthalene ring; (8) in ring B, the 5-10 membered heteroaromatic ring is (9) R 6 In some embodiments, the C1-C6alkyl is independently methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, or t-butyl. (10) R 6 In particular, the C1-C6alkoxy group is independently methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy or t-butoxy. (11) R 6 In particular, the halogen is Br.

18. The use of claim 17, wherein, The application satisfies any one of the following conditions: (1) R 2 (2) R 3 (3) R 4 (4) R 5 (5) R b (6) R c (7) R (8) R (9) R (10) R (11) R (12) R (13) R (14) R (15) R (16) R (17) R (18) R (19) R (20) R (21) R (22) (2) R 5 and R 5-1 wherein said C1-C6alkoxy is independently methoxy; (3) In L, the C1-C6 alkylene is -CH2-, -CH2CH2-, -CH(CH3)- or -CH2CH2CH2-; (4) In L, the *-COOC1-C6 alkylene is *-COO-CH2CH2CH(CH3)-; (5) R 6 In particular, the C1-C6alkyl is independently methyl. (6) R 6 In particular, the C1-C6alkoxy is independently methoxy.

19. Use according to any one of claims 16 to 18, wherein The application satisfies any one of the following conditions: (1) the compound of Formula VII is (2) the compound of Formula VIII is

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