WO2023030279A1 - 一种3，3-二氟烯丙基鎓盐类化合物及其制备方法与应用 - Google Patents

一种3，3-二氟烯丙基鎓盐类化合物及其制备方法与应用 Download PDF

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WO2023030279A1
WO2023030279A1 PCT/CN2022/115642 CN2022115642W WO2023030279A1 WO 2023030279 A1 WO2023030279 A1 WO 2023030279A1 CN 2022115642 W CN2022115642 W CN 2022115642W WO 2023030279 A1 WO2023030279 A1 WO 2023030279A1
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substituted
alkyl
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张新刚
闵巧桥
冯笑甜
高兴
任金秀
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中国科学院上海有机化学研究所
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Definitions

  • the invention relates to a 3,3-difluoroallylium salt compound and its preparation method and application, in particular, to a 3,3-difluoroallylsulfonium salt, selenium salt, tellurium Salt compound and its preparation method and application.
  • ⁇ -aryl, heteroaryl, alkenyl, alkynyl, alkyl- ⁇ , ⁇ -difluoroallyl structure compounds and their derivatives are widely used in biomedicine, pesticides and materials science .
  • some important fluorine-containing drugs KAG-308, Glecaprevir, Tafluprost, etc. all contain ⁇ , ⁇ -difluoroallyl structure.
  • Transition-metal-catalyzed ⁇ -aryl, heteroaryl or alkenyl- ⁇ , ⁇ -difluoroalkyl structural compounds and their derivatives developed in the past two decades for building-block synthesis ((a) Schwaebe, M.K.; McCarthy , J.R.; Whitten, J.P. Tetrahedron Lett.2000, 41, 791. (b) Feng, Z.; Chen, F.; Zhang, X.Org. Lett.2012, 14, 1938. (c) Bel Subscribe, M.-C. ; Poisson, T.; Pannecouke, X. Org. Lett. 2013, 15, 3428; (d) Taguchi, T.; Kitagawa, O.; H.; Kobayashi, Y.
  • the technical problem to be solved by the present invention is to overcome the relatively large structural restrictions of the ⁇ , ⁇ -gem-difluoroallyl reagent in the existing ⁇ , ⁇ -gem-difluoroallylation reaction, low controllability of the reaction activity, and suitable substrates. sexual limitations, etc.
  • the object of the present invention is to provide a novel, structurally diverse, reactivity-adjustable ⁇ , ⁇ -gem-difluoroallylating reagent (i.e. 3,3-difluoroallylsulfonium salt, selenium salt , tellurium salts and their derivatives), and apply them in a new method of more broad-spectrum and cheap ⁇ , ⁇ -gem-difluoroallylation.
  • the present invention solves the above-mentioned technical problems through the following technical solutions.
  • the present invention provides a 3,3-difluoroallyl onium salt as shown in formula C,
  • Z S, Se or Te
  • X is an anion
  • R 1 , R 2 , R 3 and R 4 are independently H, F, Cl, Br, I, C 1 -C 20 alkyl, C 1 -C 20 alkyl substituted by one or more R 5 , C 1 -C 20 heteroalkyl, C 1 -C 20 heteroalkyl substituted by one or more R 6 , C 6 -C 20 aryl, C 6 substituted by one or more R 7 -C 20 aryl, 5-20-membered heteroaryl or 5-20-membered heteroaryl substituted by one or more R 8 ; wherein, the C 1 -C 20 heteroalkyl heteroaryl
  • R1 and R4 form together with the attached Z: 5-20 membered heterocycloalkyl, 5-20 membered heterocycloalkyl substituted by one or more R9 , 5-20 membered heteroaryl A group or a 5-20 membered heteroaryl group substituted by one or more R 10 ;
  • R 1' , R 2' , R 3' and R 4' is independently C 1 -C 20 alkyl, C 3 -C 20 cycloalkyl, C 6 -C 20 aryl, replaced by one or C 1 -C 20 alkyl substituted by R 1a , C 3 -C 20 cycloalkyl substituted by one or more R 1b , C 6 -C 20 substituted by one or more R 1c Aryl;
  • R 1a , R 1b , R 1c , R 1d , R 1f and R 1e is independently F, Cl, Br, I, N 3 , C 1 -C 20 alkyl, C 6 -C 20 aryl Or a silyl group independently substituted by three C 1 -C 4 alkyl groups.
  • Z S, Se or Te
  • X is an anion
  • the R 1 , R 2 , R 3 and R 4 are independently H, F, Cl, Br, I, C 1 -C 20 alkyl, C 1 -C 20 substituted by one or more R 5 Alkyl, C 1 -C 20 heteroalkyl, C 1 -C 20 heteroalkyl substituted by one or more R 6 , C 6 -C 20 aryl, substituted by one or more R 7 C 6 -C 20 aryl, 5-20 membered heteroaryl or 5-20 membered heteroaryl substituted by one or more R 8 ; wherein, the C 1 -C 20 heteroalkyl
  • R1 and R4 form together with the attached Z: 5-20 membered heterocycloalkyl, 5-20 membered heterocycloalkyl substituted by one or more R9 , 5-20 membered heteroaryl A group or a 5-20 membered heteroaryl group substituted by one or more R 10 ;
  • R 1' , R 2' , R 3' and R 4' is independently C 1 -C 20 alkyl, C 3 -C 20 cycloalkyl, C 6 -C 20 aryl, replaced by one or C 1 -C 20 alkyl substituted by R 1a , C 3 -C 20 cycloalkyl substituted by one or more R 1b , C 6 -C 20 substituted by one or more R 1c Aryl;
  • R 1a , R 1b , R 1c , R 1d and R 1e is independently F, Cl, Br, I, N 3 , C 1 -C 20 alkyl.
  • certain groups in the 3,3-difluoroallylium salt shown in formula C are defined as follows, and the unmentioned groups are the same as any Scheme described (hereinafter referred to as "in a certain scheme of the present invention"), wherein,
  • X is a conventional anion, such as an organic or inorganic anion common in the art, such as trifluoromethanesulfonate anion, fluoroboric acid anion, hexafluorophosphate anion, hexafluoroantimonate anion, p-toluenesulfonate anion, fluoride anion, Chloride anion, bromide anion, iodide anion, etc.
  • an organic or inorganic anion common in the art, such as trifluoromethanesulfonate anion, fluoroboric acid anion, hexafluorophosphate anion, hexafluoroantimonate anion, p-toluenesulfonate anion, fluoride anion, Chloride anion, bromide anion, iodide anion, etc.
  • X is a conventional anion, such as an organic or inorganic anion common in the art, such as tetraphenylborate anion, trifluoromethanesulfonate anion, fluoroborate anion, hexafluorophosphate anion, hexafluoroantimonate anion, p-toluenesulfonic acid anion, fluoride anion, chloride anion, bromide anion, iodide anion, etc.
  • an organic or inorganic anion common in the art, such as tetraphenylborate anion, trifluoromethanesulfonate anion, fluoroborate anion, hexafluorophosphate anion, hexafluoroantimonate anion, p-toluenesulfonic acid anion, fluoride anion, chloride anion, bromide anion, iodide anion, etc.
  • the C 1 -C 20 alkyl group in any of the above-mentioned C 1 -C 20 alkyl groups and substituted C 1 -C 20 alkyl groups is independently C 1 -C 10 alkyl, such as C 1 -C 6 alkyl, also such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, n-hexyl (nC 6 H 13 ) or tert-butyl.
  • the C 1 -C 20 alkyl group in any of the above-mentioned C 1 -C 20 alkyl groups and substituted C 1 -C 20 alkyl groups is independently C 1 -C 10 alkyl, another example is C 1 -C 6 alkyl, also for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.
  • the C 2 -C 20 alkynyl group in any of the above-mentioned C 2 -C 20 alkynyl groups and substituted C 2 -C 20 alkynyl groups is independently C 2 -C 10 alkynyl, and C 2 -C 6 alkynyl, also as
  • the C 2 -C 20 alkenyl in any of the above -mentioned C 2 -C 20 alkenyl groups and substituted C 2 -C 20 alkenyl groups is independently C 2 -C 10 alkenyl, and C 2 -C 6 alkenyl, also as
  • the C 6 -C 20 aryl group in any of the above C 6 -C 20 aryl groups and substituted C 6 -C 20 aryl groups is independently phenyl .
  • R 1 and R 4 as described above together with the connected Z form: 5-20 membered heterocycloalkyl, substituted 5-20 membered heterocycloalkyl
  • the 5-20 membered heterocycloalkyl group is independently a 5-10 membered heterocycloalkyl group, for example
  • any one of the above C 3 -C 20 cycloalkyl groups is independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
  • said R 4 is independently a C 1 -C 20 alkyl group, preferably a C 1 -C 6 alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.
  • R 4 is independently Me or Et.
  • one of R and R is Me or Et , and the other is phenyl, tolyl, methoxyphenyl, bromophenyl, tri(methyl)phenyl, Tris(isopropyl)phenyl, phenylethylene.
  • R 1 and R 4 form together with connected Z:
  • Alkyl is independently the C 1 -C 20 alkyl, C 1 -C 20 alkyl substituted by one or more R 5 ; for example
  • the 3,3-difluoroallylium salt shown in formula C is any of the following structures:
  • X is F, Cl, Br, BF 4 , OTf, BPh 4 , PF 6 , TeF 6 or SbF 6
  • TIPP is tri(isopropyl)phenyl
  • Mes is 2,4 , 6-trimethylphenyl
  • Tol is tolyl
  • Alkyl is independently the C 1 -C 20 alkyl group, the C 1 -C 20 alkyl group substituted by one or more R 5
  • Ar is independently The C 6 -C 20 aryl group, the C 6 -C 20 aryl group substituted by one or more R 7 ; the definitions of R 5 and R 7 are as described in the present invention.
  • the 3,3-difluoroallylium salt shown in formula C is any one of the following compounds:
  • the present invention provides a preparation method of 3,3-difluoroallylium salt compounds as shown in formula C, which comprises the following steps:
  • the compound shown in the formula D is subjected to an alkylation reaction with an alkylating agent to obtain a 3,3-difluoroallylium salt compound shown in the formula C;
  • the alkylating agent is a system of R 4 X and/or R 4 I and AgX or R 4 3 OBF 4 ;
  • the alkylating agent can be R 4 X, such as MeOTf.
  • the alkylating agent may be (R 4 ) 3 OBF 4 , such as (Et) 3 OBF 4 .
  • the organic solvent can be an aprotic solvent, such as DCM, THF, DMF or DMSO.
  • the amount of the organic solvent may not be specifically limited so as not to affect the reaction; in the present invention, the mass of the compound shown in formula D and the organic solvent
  • the volume ratio is preferably 0.01mol/L-2mol/L (for example, 0.7mol/L-1mol/L).
  • the molar ratio of the compound represented by formula D to the alkylating agent can be 1:0.8 to 1:1.5, for example 1:0.9, 1:1, 1.12:1, 1.15:1, 1:0.933 or 1:1.1.
  • the molar ratio of the compound represented by formula D to the alkylating agent may be 1:0.9 to 1:1.5, such as 1:1, 1.15:1.
  • the alkylation reaction is preferably carried out under argon or nitrogen.
  • the alkylation reaction is preferably carried out at a temperature of 0°C to 140°C, such as 10 to 30°C.
  • the progress of the described reaction can be monitored by conventional monitoring methods in the art (such as TLC or NMR), generally when the compound shown in the formula D disappears or no longer reacts is the end point of the reaction.
  • the preparation method also includes the preparation method of the compound shown in formula D, which includes the following steps: in an organic solvent, the compound shown in formula A and the compound shown in formula B The compound undergoes the substitution reaction shown in the following formula, and the obtained compound shown in the formula D can be obtained;
  • X1 is F, Cl or Br; M1 is an alkali metal.
  • M 1 is Na, K or Li.
  • the operation and conditions of the described substitution reaction can be conventional operations and conditions in this type of reaction in the art; preferably as follows in the present invention,
  • the organic solvent can be an aprotic solvent, such as dioxane (dioxane), tetrahydrofuran (THF), N,N-dimethylformamide (DMF) and dimethyl One or more of sulfoxide (DMSO).
  • dioxane dioxane
  • THF tetrahydrofuran
  • DMF N,N-dimethylformamide
  • DMSO dimethyl One or more of sulfoxide
  • the amount of the organic solvent can not be specifically limited, so as not to affect the reaction; in the present invention, the mass volume of the compound shown in formula B is compared with the organic solvent Preferably, it is 0.01mol/L-2mol/L (for example, 0.7mol/L-1mol/L).
  • the compound represented by formula B can be added in the form of a conventional solution, such as a THF solution, and for example a 1.2M THF solution.
  • the molar ratio of the compound shown in formula A to the compound shown in formula B can be from 1:1 to 1:3, such as 1:1.2, 1:1.25, 1:2 , 1:1.67, 1:1.335.
  • the molar ratio of the compound shown in formula A to the compound shown in formula B can be from 1:1 to 1:3, such as 1:1.2, 1:1.25, 1:2 .
  • the substitution reaction is preferably carried out under argon or nitrogen.
  • the substitution reaction is preferably carried out at room temperature to 140°C, preferably at 50°C to 140°C, for example 100 ⁇ 10°C.
  • the progress of the described reaction can be monitored by conventional monitoring methods in the art (such as TLC or NMR), generally when the compound shown in formula A disappears or no longer reacts, the reaction is end.
  • the present invention also provides the application of a 3,3-difluoroallylium salt compound represented by the above formula C as an ⁇ , ⁇ -gem-difluoroallylating reagent.
  • reaction selectivity of the 3,3-difluoroallylium salt compound represented by the formula C can be adjusted through the steric hindrance and electrical effects of R 1 or R 4 .
  • the application includes the steps of:
  • the 3,3-difluoroallylium salt compound shown in formula C is coupled with a zinc reagent as shown below to obtain ⁇ , ⁇ -gem difluoro Allyl compounds can be;
  • [C] represents a part linked to [Zn] via Csp1, Csp2 or Csp3; [Zn] represents ZnX 2 , Zn ⁇ LiX 2 , ZnX 2 ⁇ LiX 2 ; X 2 is independently bromine or chlorine.
  • the [Zn] is ZnBr, ZnCl, Zn ⁇ LiCl, ZnCl ⁇ LiCl, ZnBr ⁇ LiCl.
  • the operation and conditions of the coupling reaction can be conventional operations and conditions in this type of reaction in the art. In the present invention, it can be preferably as follows:
  • the solvent may be an ether solvent; the ether solvent is tetrahydrofuran.
  • the amount of the organic solvent may not be specifically limited, so as not to affect the reaction; in the present invention, the mass volume of the compound shown in formula C is compared with the organic solvent Preferably, it is 0.01mol/L-2mol/L (for example, 0.1mol/L).
  • the zinc reagent can be added in the form of a conventional solution, such as dimethylacetamide (DMA) and/or THF solution, and for example 0.1 to 1M DMA and/or THF solution.
  • DMA dimethylacetamide
  • THF trifluoride
  • the molar ratio of the 3,3-difluoroallylium salt compound represented by the formula C to the zinc reagent can be 1:1 to 1.5; for example, 1:1.1, 1:1. 1.2, 1:1.3.
  • the coupling reaction is carried out in the presence of a catalyst, and the catalyst can be a cuprous halide, such as CuBr; the catalyst and the 3,3-difluoroallyl onium salt shown in the formula C
  • the molar ratio of the quasi-compounds may range from 0.2 to 0.005; eg 0.01, 0.025, 0.05, 0.1.
  • the temperature of the coupling reaction can be -78 to 35°C, for example, at room temperature.
  • the progress of the reaction can be monitored by conventional monitoring methods in the art (such as TLC or NMR), and generally the end point of the reaction is when the compound represented by formula C disappears or no longer reacts.
  • the zinc reagent and the corresponding ⁇ , ⁇ -gem-difluoroallyl compound shown in formula E are any one of the following groups:
  • groups and substituents thereof can be selected by those skilled in the art to provide stable moieties and compounds.
  • substituents When a substituent is described by a conventional chemical formula written from left to right, the substituent also includes chemically equivalent substituents obtained when the structural formula is written from right to left.
  • C 1 -C 6 alkyl refers to 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 abbreviated notation does not include carbons that may be present in substituents of the stated group.
  • substituted means that any one or more hydrogen atoms on a specified atom are replaced by a substituent, as long as the valence of the specified atom is normal and the substituted compound is stable.
  • substituted means that one or more hydrogen atoms in a given structure have been replaced by a particular substituent.
  • the substituents are independent of each other, that is, the one or more substituents may be different from each other or the same of.
  • a substituent may substitute at each substitutable position of the substituent. When more than one position in a given formula can be substituted by one or more substituents selected from a particular group, then the substituents can be substituted at each position the same or differently.
  • C x -C y alkyl refers to a straight or branched chain saturated hydrocarbon containing x to y carbon atoms.
  • C 1 -C 6 alkyl or "C 1-6 alkyl” specifically refers to independently disclosed methyl, ethyl, C 3 alkyl, C 4 alkyl, C 5 alkyl and C 6 alkane
  • C 1-4 alkyl specifically refers to independently disclosed methyl, ethyl, C 3 alkyl (ie propyl, including n-propyl and isopropyl), C 4 alkyl (ie butyl, including n-butyl, isobutyl, sec-butyl and tert-butyl).
  • moiety refers to a specific segment or functional group in a molecule. Chemical moieties are generally considered to be chemical entities embedded or attached to molecules.
  • variable such as R 1a
  • the definition at each position of the variable has nothing to do with the definitions at other positions, and their meanings are independent of each other and do not affect each other. Therefore, if a group is substituted by 1, 2 or 3 R 1a groups, that is, the group may be substituted by up to 3 R 1a groups , the definition of R 1a in this position is the same as that of the remaining R 1a groups Definitions are independent of each other. Also, combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.
  • linking substituents are described.
  • the Markush variables recited for that group are to be understood as linking groups.
  • the Markush group definition for that variable recites “alkyl,” it is understood that “alkyl” represents a linking alkylene group.
  • alkyl group when an alkyl group is clearly indicated as a linking group, then the alkyl group represents a linked alkylene group, for example, the group "halo-C 1 -C 6 alkane C 1 -C 6 alkyl in "group” should be understood as C 1 -C 6 alkylene.
  • halogen means fluorine, chlorine, bromine or iodine, especially F or Cl.
  • alkyl as a group or part of another group (such as used in haloalkyl, deuterated alkyl, etc. groups), is meant to include branched and straight chains with the specified number of carbon atoms.
  • a chain of saturated aliphatic hydrocarbon groups consisting only of carbon and hydrogen atoms attached to the rest of the molecule by single bonds. For example, it has 1 to 20 (preferably 1 to 10, more preferably 1 to 6, more preferably 1 to 4) carbon atoms.
  • propyl is C 3 alkyl (including isomers, such as n-propyl or isopropyl); butyl is C 4 alkyl (including isomers, such as n-butyl, sec-butyl , isobutyl or tert-butyl); pentyl is C 5 alkyl (including isomers, such as n-pentyl, 1-methyl-butyl, 1-ethyl-propyl, 2-methyl -1-butyl, 3-methyl-1-butyl, isopentyl, tert-pentyl or neopentyl); hexyl is C 6 alkyl (including isomers, such as n-hexyl, 1-ethyl Base-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl , 1,3-dimethylbutyl, 2-ethylbut
  • Examples include but are not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2- Dimethylpropyl, n-hexyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, n-octyl, nonyl, decyl and similar alkyl groups.
  • alkylene means a saturated divalent hydrocarbon group obtained by removing two hydrogen atoms from a saturated linear or branched chain hydrocarbon group; i.e. One hydrogen in the alkyl group is substituted, the definition of alkyl group is as above.
  • alkylene groups include methylene (-CH 2 -), ethylene ⁇ including -CH 2 CH 2 - or -CH(CH 3 )- ⁇ , isopropylidene ⁇ including -CH(CH 3 )CH 2 -or -C(CH 3 ) 2 - ⁇ and so on.
  • the a-terminus represents the attachment position) to provide a heteroalkyl group (eg, an alkyl group containing one or more ether, thioether, or amino linkages).
  • alkoxy as a group or part of another group, means -O-alkyl, the definition of alkyl is as above.
  • alkylthio refers to -S-alkyl, the definition of alkyl is as above.
  • alkenyl refers to a straight or branched hydrocarbon chain having at least one double bond, consisting only of carbon atoms and hydrogen atoms, and passing through Single bonds connect with the rest of the molecule.
  • having 2 to 20 (preferably 2 to 10, more preferably 2 to 6, most preferably 2 to 4) carbon atoms, for example including but not limited to vinyl, n-propenyl, isopropenyl, n-butenyl , isobutenyl, sec-butenyl, tert-butenyl, n-pentenyl, 2-methylbutenyl, 2,2-dimethylpropenyl, n-hexenyl, heptenyl, 2-methylhexyl Alkenyl, 3-methylhexenyl, octenyl, nonenyl, decenyl, etc.
  • cycloalkyl as a group or part of another group, means a saturated monocyclic or polycyclic (such as bicyclic, tricyclic or more ) or a carbocyclic substituent of a spiro ring system), and it may be attached to the remainder of the molecule by a single bond via any suitable carbon atom.
  • a 3-20 membered cycloalkyl group having 3 to 20 carbon atoms preferably a 3-10 membered cycloalkyl group having 3 to 10 carbon atoms, more preferably a 3-7 membered cycloalkane group having 3 to 7 carbon atoms group, most preferably a 3-6 membered cycloalkyl group having 3 to 6 carbon atoms.
  • a typical monocyclic cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.
  • B P or Si heteroatoms or heteroatom groups
  • the a terminal represents a stable saturated heterocyclic hydrocarbon group consisting of the attachment position).
  • Heterocycloalkylbicyclic ring systems can include one or more heteroatoms in one or both rings; and are saturated.
  • heterocycloalkyl is a 5 to 7 membered monocyclic heterocycloalkyl, a 6 to 8 membered ring linked heterocycloalkyl, a 6 to 8 membered bridged ring linked heterocycloalkyl Or a 7- to 10-membered spiro-linked heterocycloalkyl.
  • aryl as a group or part of another group, means a conjugated hydrocarbon ring system group satisfying the 4n+2 rule.
  • conjugated hydrocarbon ring system radicals with 6 to 20 carbon atoms, preferably with 6 to 10 carbon atoms, satisfying the 4n+2 rule.
  • aryl can be a monocyclic, bicyclic, tricyclic or multicyclic ring system, and can also be combined with cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycle as defined above.
  • An alkenyl is fused, provided that the aryl is attached to the rest of the molecule by a single bond via an atom on the aromatic ring.
  • the term "aryl” refers to an aromatic group composed of carbon atoms, each ring having aromaticity. Examples of aryl include, but are not limited to, phenyl, naphthyl.
  • the a terminal represents the conjugated ring system group of the attachment position).
  • heteroaryl can be a monocyclic, bicyclic, tricyclic or multicyclic ring system, and can also be combined with the above-defined cycloalkyl, cycloalkenyl, heterocycloalkyl or A heterocycloalkenyl is fused, provided that the heteroaryl is attached to the rest of the molecule by a single bond via an atom on the aromatic ring.
  • heteroaryl preferably contains 1 to 5 stable 5 to 20 membered aromatic groups selected from nitrogen, oxygen and sulfur heteroatoms, further preferably contains 1 to 5 heteroatoms selected from nitrogen, A stable 5- to 10-membered aromatic group of oxygen and sulfur heteroatoms.
  • heteroaryl refers to an aromatic group containing heteroatoms, each ring having aromaticity; preferably containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and sulfur Atom aromatic 5-6 membered monocyclic ring or 9-10 membered bicyclic ring.
  • each step and condition can refer to the conventional operation steps and conditions in the art.
  • the present invention employs standard nomenclature and standard laboratory procedures and techniques of analytical chemistry, synthetic organic chemistry and optics. In some cases, standard techniques are used for chemical synthesis, chemical analysis, and performance testing of light-emitting devices.
  • the reagents and raw materials used in the present invention are all commercially available.
  • the positive progress effect of the present invention is that: the 3,3-difluoroallylium salt shown in formula C provided by the present invention can be used as ⁇ , ⁇ -gem difluoroallylating reagent, which is ⁇ , ⁇ - Gem difluoroallylation provides a more broad-spectrum and inexpensive new method with high efficiency and good application prospects.
  • room temperature refers to ambient temperature, which is 10°C-35°C. Overnight means 8-15 hours. Reflux refers to the solvent reflux temperature at normal pressure.
  • the zinc reagents and thioethers used in this application can be prepared by conventional methods in the art or by methods described in this application.
  • the anhydrous and oxygen-free conditions described in this application refer to carrying out the reaction under a protective gas, such as carrying out the reaction in argon (Argon or Ar refers to argon), unless otherwise specified.
  • the unit of temperature in this application is degrees Celsius (°C), specifically expressed as "°C", “degrees Celsius” or "degrees”.
  • diphenyl disulfide (8.8g, 40mmol) was added to a 100mL three-necked flask for three-time pumping, and 30mL ultra-dry n-hexane (Hexane) was added under argon (Ar), and placed at room temperature (RT Indicates room temperature) in a water bath, then, inject n-butyllithium (16.0mL, 2.5M n-hexane (Hexane) solution, 40mmol) dropwise into a syringe, (a large amount of white solid is generated, and the reaction is exothermic, and the temperature of the reaction bottle is lowered to room temperature to stop the reaction).
  • n-butyllithium (16.0mL, 2.5M n-hexane (Hexane) solution, 40mmol
  • diphenyl ditelluride (16.4g, 40mmol) into a 100mL three-necked bottle for three times of ventilation, add 30mL of ultra-dry n-hexane under Ar, place it in a water bath at room temperature, and then add n- Butyllithium (16.0mL, 2.5M n-hexane solution, 40mmol), (a large amount of white solid is formed, the reaction is exothermic, and the reaction can be stopped when the temperature of the reaction bottle drops to room temperature).
  • diphenyl diselenide (12.49g, 40mmol) into a 100mL three-necked bottle for three times of ventilation, add 30mL ultra-dry n-hexane under Ar, place in a water bath at room temperature, and then add n- Butyllithium (16.0mL, 2.5M n-hexane solution, 40mmol), (a large amount of white solid is formed, the reaction is exothermic, and the reaction can be stopped when the temperature of the reaction bottle drops to room temperature).
  • diphenyl ditelluride (16.4g, 40mmol) into a 100mL three-necked bottle for three times of ventilation, add 30mL of ultra-dry n-hexane under Ar, place it in a water bath at room temperature, and then add n- Butyllithium (16.0mL, 2.5M n-hexane solution, 40mmol), (a large amount of white solid is formed, the reaction is exothermic, and the reaction can be stopped when the temperature of the reaction bottle drops to room temperature).
  • thioether (10.7mmol, 2.32g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (1.5ml) was added, followed by MeOTf (1.03ml, 9.75mmol), and reacted at room temperature for 12h.
  • MeOTf (1.03ml, 9.75mmol)
  • Spin dry then add methanol to dissolve, wash with n-hexane (layered), wash until the fluorescence of the n-hexane layer is extremely weak, then spin dry methanol, and drain to obtain 3.9g, viscous liquid, yield 92%.
  • thioether 10mmol, 2.32g was added to a 50mL round bottom flask, followed by ultra-dry DCM (15ml), and then triethyloxonium tetrafluoroborate (2.09g, 11mmol), Reaction at room temperature for 36h. Spin dry, then add methanol to dissolve, wash with n-hexane (layering), wash until the fluorescence of the n-hexane layer is extremely weak, then spin dry methanol, and drain to obtain 1.5 g of viscous liquid, yield 45%.
  • thioether (12.2mmol, 3.24g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (10ml) was added, followed by MeOTf (1.2ml, 11.2mmol), and reacted at room temperature for 12h.
  • MeOTf 1.2ml, 11.2mmol
  • thioether (16.5mmol, 4.6g) was added to a 100mL three-necked flask, ultra-dry DCM (10ml) was added, and then MeOTf (2.5g, 15mmol) was added, and reacted at room temperature for 4h.
  • Spin dry then add methanol to dissolve, wash with n-hexane (layered), wash until the fluorescence of the n-hexane layer is extremely weak, then spin dry methanol, and recrystallize with ether to obtain 5.5 g of white solid with a yield of 83%.
  • thioether (1.18g, 5.0mmol) was added to a 100mL three-necked flask, ultra-dry DCM (10ml) was added, and then MeOTf (0.72g, 4.3mmol) was added, and the reaction was carried out at room temperature for 4h. Spin dry, then add methanol to dissolve, wash with n-hexane (layered), wash until the fluorescence of the n-hexane layer is extremely weak, then spin dry methanol, and recrystallize with ether to obtain 1.9 g of white solid with a yield of 92%.
  • thioether (12.2mmol, 2.62g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (10ml) was added, followed by MeOTf (1.2ml, 11.2mmol), and reacted at room temperature for 12h.
  • MeOTf 1.2ml, 11.2mmol
  • thioether (12.2mmol, 3.37g) was added to a 50mL round-bottomed flask, ultra-dry DCM (10ml) was added, and then MeOTf (1.2ml, 11.2mmol) was added, and reacted at room temperature for 12h. Spin dry, then add methanol to dissolve, wash with n-hexane (layered), wash until the fluorescence of the n-hexane layer is extremely weak, then spin dry methanol, and drain to obtain 4.44g viscous liquid, yield 90%.
  • thioether (12.2mmol, 3.72g) was added to a 50mL round-bottomed flask, ultra-dry DCM (10ml) was added, and then MeOTf (1.2ml, 11.2mmol) was added, and reacted at room temperature for 12h. Spin dry, then add methanol to dissolve, wash with n-hexane (layered), wash until the fluorescence of the n-hexane layer is extremely weak, then spin dry methanol, and drain to obtain 4.62g viscous liquid, yield 88%.
  • thioether (12.2mmol, 4.08g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (10ml) was added, followed by MeOTf (1.2ml, 11.2mmol), and reacted at room temperature for 12h.
  • MeOTf 1.2ml, 11.2mmol
  • thioether (12.2mmol, 3.67g) was added to a 50mL round-bottomed flask, ultra-dry DCM (10ml) was added, and then MeOTf (1.2ml, 11.2mmol) was added, and reacted at room temperature for 12h. Spin dry, then add methanol to dissolve, wash with n-hexane (layered), wash until the fluorescence of the n-hexane layer is extremely weak, then spin dry methanol, and drain to obtain 4.37g viscous liquid, yield 84%.
  • thioether (12.2mmol, 4.04g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (10ml) was added, followed by MeOTf (1.2ml, 11.2mmol), and reacted at room temperature for 12h.
  • MeOTf 1.2ml, 11.2mmol
  • thioether (12.2mmol, 2.62g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (10ml) was added, followed by MeOTf (1.2ml, 11.2mmol), and reacted at room temperature for 12h.
  • MeOTf 1.2ml, 11.2mmol
  • thioether (12.2mmol, 3.15g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (10ml) was added, followed by MeOTf (1.2ml, 11.2mmol), and reacted at room temperature for 12h.
  • MeOTf 1.2ml, 11.2mmol
  • thioether (12.2mmol, 3.91g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (10ml) was added, followed by MeOTf (1.2ml, 11.2mmol), and reacted at room temperature for 12h.
  • MeOTf 1.2ml, 11.2mmol
  • thioether (12.2mmol, 4.05g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (10ml) was added, followed by MeOTf (1.2ml, 11.2mmol), and reacted at room temperature for 12h.
  • MeOTf 1.2ml, 11.2mmol
  • thioether (12.2mmol, 2.91g) was added to a 50mL round-bottomed flask, and ultra-dry DCM (10ml) was added, followed by MeOTf (1.2ml, 11.2mmol), and reacted at room temperature for 12h.
  • MeOTf 1.2ml, 11.2mmol
  • the product from the previous step and phenethanethiol were added to a solution of potassium carbonate (2.0 equiv.) in methanol, and stirred overnight at room temperature.
  • the reaction system was filtered, spin-dried, and subjected to column chromatography to obtain the target compound, and the following compounds were prepared in this way.
  • the catalyst was weighed under air; the target compound means the target compound; SM1 means the raw material, 19 F% means the yield measured by 19 F NMR with fluorobenzene as the internal standard; ND means not detected.
  • the temperature of the coupling reaction in this step is not particularly limited, and can be carried out within the range of -78 to 35°C.
  • ND means not detected.
  • 19 F% refers to the yield determined by 19 F NMR with fluorobenzene as the internal standard; ND means not detected. c CuCl (99.999%) used.
  • Catalyst consumption is shown in the table below:
  • trace means trace
  • reaction operation and conditions refer to the above-mentioned examples (application example pre-test), and the zinc reagent shown in the following table is reacted, and the reaction results are shown in the following table.
  • Step (1) Add 2.5mol% CuBr into a 25mL Shrek bottle, add difluoroallyl onium salt (0.5mmol, 1.0equiv) represented by formula C, vacuumize and fill with Ar three times. 2.0 mL of THF was added, and the zinc reagent (1.2 equiv) represented by the formula [C]-[Zn] was added dropwise and stirred at room temperature for 3 hours to react.
  • the product yield was determined by 19 F NMR using fluorobenzene as an internal standard reagent, the reaction was quenched with NH 4 Cl and diluted with EtOAc to dry, the aqueous phase was washed with ethyl acetate (3 ⁇ 10 mL), and the organic phase was dried with Na 2 SO 4 . filter, collect. The product after chromatographic purification was directly used in the next step of preparation.
  • Step (2) At 25°C, add K 2 OsO 2 (OH) 4 (9.2mg, 5mol%), NMO (135mg, 1mmol, 2.0equiv) and the above compound into a 25mL flask and stir for 24h, dilute with ethyl acetate, Washed with saturated NaHCO3 , brine, dried over Na2SO4 , filtered and concentrated . Chromatography on silica gel affords the following product.
  • the obtained intermediate obtained the target product by reducing the double bond with Pd/C.
  • the reduction conditions were as follows: Pd/C (21.2 mg, 10%) and the above product 0.2 mmol were added to 2 mL of DCM, and H 2 (1 atm) was introduced at room temperature for 24 h.

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Abstract

提供了一种如式(C)所示的3,3-二氟烯丙基鎓盐，及该类物质的制备方法；使用廉价工业原料制备得到该重要的含氟试剂；其可作为α,α-偕二氟烯丙基化试剂，为α,α-偕二氟烯丙基化提供了更加普适和廉价的新方法，其效率高，应用前景较佳。

Description

一种3，3-二氟烯丙基鎓盐类化合物及其制备方法与应用
本申请要求申请日为2021/9/01日的中国专利申请202111021362.5的优先权。本申请引用上述中国专利申请的全文。
技术领域
本发明涉及一种3，3-二氟烯丙基鎓盐类化合物及其制备方法与应用，具体地，涉及一种3，3-二氟烯丙基硫鎓盐、硒鎓盐、碲鎓盐类化合物及其制备方法与应用。
背景技术
α-芳基、杂芳基、烯基、炔基、烷基-α,α-二氟烯丙基结构化合物及其衍生物砌块在生物医药、农药和材料科学等方面都有着广泛的应用。例如：一些重要含氟药物KAG-308，Glecaprevir,Tafluprost等都含有α,α-二氟烯丙基结构。
然而，传统的合成α-芳基、杂芳基、烯基、炔基、烷基-α,α-二氟烷基砌块的方法中，通常是由羰基通过DAST或者Deoxofluor制得(例如，Markovsi,L.N.；Pahinnik,V.E.；Kirsanov,A.V.Synthesis 1973,787.(b)Middleton,W.J.J.Org.Chem.1975,40,574.(c)Lal,G.S.；Pez,G.P.；Pesaresi,R.J.；Prozonic,F.M.；Cheng,H.J.Org.Chem.1999,64,7048.)。但是，这些方法通常具有反应步骤冗长、官能团兼容性不好、某些反应需要用到一些剧毒的氟化剂等缺点。
近二十年发展的过渡金属催化的α-芳基、杂芳基或烯基-α,α-二氟烷基结构化合物及其衍生物的砌块合成方法((a)Schwaebe,M.K.；McCarthy,J.R.；Whitten,J.P.Tetrahedron Lett.2000,41,791.(b)Feng,Z.；Chen,F.；Zhang,X.Org.Lett.2012,14,1938.(c)Belhomme,M.-C.；Poisson,T.；Pannecouke,X.Org.Lett.2013,15,3428；(d)Taguchi,T.；Kitagawa,O.；Morikawa,T.；Nishiwaki,T.；Uehara,H.；Endo,H.；Kobayashi,Y.Tetrahedron Lett.1986,27,6103.(e)Sato,K.；Omote,M.；Ando,A.；Kumadaki,I.J.Fluorine Chem.2004,125,509.(f)Qiu,W.；Burton,D.J.Tetrahedron Lett.1996,37,2745.(g)Yokomatsu,T.；Murano,T.；Suemune,K.；Shibuya,S.Tetrahedron 1997,53,815.)在一定程度上解决了这类化合物合成的困难。但是，这些方法仍然存在诸如：官能团兼容性不好、催化剂用量高、反应条件苛刻等不足。
2014年，钯催化的亲核试剂与α-溴代-α,α-二氟烯丙基试剂的偶联反应(J.Am.Chem.Soc.2014,136,1230；ZL 2013 1 0658890.0)简化了α-芳基、杂芳基、烯基-α,α-二氟烯丙基类结构的合成方法，但是该反应仍然存在以下限制：1.受α-溴代-α,α-二氟烯丙基试剂合成的限制，产物的结构多样性还有待进一步突破；2.由于α-溴代-α,α-二氟烯丙基试剂的活性较高，该反应仅适用于部分Csp2的亲核试剂，难以适用于Csp和Csp3碳类的亲核试剂；3.钯催化剂价格较高，需要探寻一些更廉价和毒性更低的催化剂。
对于Csp3碳类的亲核试剂参与的α,α-二氟烯丙基化反应形成的烷基-α,α-二氟烯丙基结构化合物，目前还鲜有合适的试剂和方法能够高效实现，目前仅有一例结构非常特殊、高度活化的Csp3碳亲核 试剂参与的α,α-二氟烯丙基试剂的反应被报道(Nature Communication,2021,12:3257)。对于其他类型的α,α-二氟烯丙基试剂(Synlett.1996,4,371；Chem.Pharm.Bull.1985,33(11),5137)，其制备方法通常较为繁琐，并且其参与的反应往往存在区域选择性难以控制、会发生脱氟副反应、反应条件苛刻、反应底物和类型受限等原因而难以实现广谱性地、高效率地制备预期的产物结构。
因此，发展一类新型的、结构多样的、反应活性可调节的α,α-偕二氟烯丙基化试剂并将其应用于更加广谱和廉价的α,α-偕二氟烯丙基化新方法中具有显著的意义。
发明内容
本发明所要解决的技术问题在于克服现有α,α-偕二氟烯丙基化反应中α,α-偕二氟烯丙基试剂结构限制较大、反应活性可控性低、底物适用性受限等缺陷。本发明的目是提供一种新型的、结构多样的、反应活性可调节的α,α-偕二氟烯丙基化试剂(即3，3-二氟烯丙基硫鎓盐、硒鎓盐、碲鎓盐及其衍生物)，并将其应用于更加广谱和廉价的α,α-偕二氟烯丙基化新方法中。
本发明是通过下述技术方案来解决上述技术问题的。
本发明提供了一种如式C所示的3，3-二氟烯丙基鎓盐，
Figure PCTCN2022115642-appb-000001
其中，Z＝S，Se或Te；X为阴离子；
R 1、R 2、R 3和R 4独立地为H、F、Cl、Br、I、C 1-C 20的烷基、被一个或多个R 5取代的C 1-C 20的烷基、C 1-C 20的杂烷基、被一个或多个R 6取代的C 1-C 20的杂烷基、C 6-C 20的芳基、被一个或多个R 7取代的C 6-C 20的芳基、5-20元的杂芳基或被一个或多个R 8取代的5-20元的杂芳基；其中，所述的C 1-C 20的杂烷基的杂原子或杂原子团选自C(＝O)、S(＝O)、S(＝O) 2、SO 2NR 1’R 2’、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；所述的5-20元的杂芳基的杂原子选自S、O、N、Si、P和B，杂原子个数为1个或多个；
或者，R 1和R 4与相连的Z一起形成：5-20元的杂环烷基、被一个或多个R 9取代的5-20元的杂环烷基、5-20元的杂芳基或被一个或多个R 10取代的5-20元的杂芳基；所述的5-20元的杂环烷基的杂原子或杂原子团选自C(＝O)、S、S(＝O)、S(＝O) 2、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；所述的5-20元的杂芳基的杂原子或杂原子团选自C(＝O)、S、S(＝O)、S(＝O) 2、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；
每个R 5、R 6、R 7、R 8、R 9和R 10独立地为F、Cl、Br、I、C 1-C 20的烷基、C 3-C 20的环烷基、C 6-C 20的芳基、C 2-C 20的炔基、C 2-C 20的烯基、C 1-C 20的杂烷基、被一个或多个R 1a取代的C 1-C 20的烷基、被一个或多个R 1b取代的C 3-C 20的环烷基、被一个或多个R 1c取代的C 6-C 20的芳基、一个或多个R 1d取 代的C 2-C 20的炔基、被一个或多个R 1e取代的C 1-C 20的杂烷基、被一个或多个R 1f取代的C 2-C 20的烯基；所述的C 1-C 20的杂烷基的杂原子或杂原子团选自C(＝O)、S(＝O)、S(＝O) 2、SO 2NR 1’R 2’、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；
每个R 1’、R 2’、R 3’和R 4’独立地为C 1-C 20的烷基、C 3-C 20的环烷基、C 6-C 20的芳基、被一个或多个R 1a取代的C 1-C 20的烷基、被一个或多个R 1b取代的C 3-C 20的环烷基、被一个或多个R 1c取代的C 6-C 20的芳基；
每个R 1a、R 1b、R 1c、R 1d、R 1f和R 1e独立地为F、Cl、Br、I、N 3、C 1-C 20的烷基、C 6-C 20的芳基或独立地被三个C 1-C 4烷基取代的硅烷基。
在本发明的某一方案中，如式C所示的3，3-二氟烯丙基鎓盐，
Figure PCTCN2022115642-appb-000002
其中，Z＝S，Se或Te；X为阴离子；
所述R 1、R 2、R 3和R 4独立地为H、F、Cl、Br、I、C 1-C 20的烷基、被一个或多个R 5取代的C 1-C 20的烷基、C 1-C 20的杂烷基、被一个或多个R 6取代的C 1-C 20的杂烷基、C 6-C 20的芳基、被一个或多个R 7取代的C 6-C 20的芳基、5-20元的杂芳基或被一个或多个R 8取代的5-20元的杂芳基；其中，所述的C 1-C 20的杂烷基的杂原子或杂原子团选自C(＝O)、S(＝O)、S(＝O) 2、SO 2NR 1’R 2’、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；所述的5-20元的杂芳基的杂原子选自S、O、N、Si、P和B，杂原子个数为1个或多个；
或者，R 1和R 4与相连的Z一起形成：5-20元的杂环烷基、被一个或多个R 9取代的5-20元的杂环烷基、5-20元的杂芳基或被一个或多个R 10取代的5-20元的杂芳基；所述的5-20元的杂环烷基的杂原子或杂原子团选自C(＝O)、S、S(＝O)、S(＝O) 2、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；所述的5-20元的杂芳基的杂原子或杂原子团选自C(＝O)、S、S(＝O)、S(＝O) 2、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；
所述R 5、R 6、R 7、R 8、R 9和R 10独立地为F、Cl、Br、I、C 1-C 20的烷基、C 3-C 20的环烷基、C 6-C 20的芳基、C 2-C 20的炔基、C 1-C 20的杂烷基、被一个或多个R 1a取代的C 1-C 20的烷基、被一个或多个R 1b取代的C 3-C 20的环烷基、被一个或多个R 1c取代的C 6-C 20的芳基、一个或多个R 1d取代的C 2-C 20的炔基、被一个或多个R 1e取代的C 1-C 20的杂烷基；所述的C 1-C 20的杂烷基的杂原子或杂原子团选自C(＝O)、S(＝O)、S(＝O) 2、SO 2NR 1’R 2’、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；
每个R 1’、R 2’、R 3’和R 4’独立地为C 1-C 20的烷基、C 3-C 20的环烷基、C 6-C 20的芳基、被一个或多个R 1a取代的C 1-C 20的烷基、被一个或多个R 1b取代的C 3-C 20的环烷基、被一个或多个R 1c取代的C 6-C 20 的芳基；
每个R 1a、R 1b、R 1c、R 1d和R 1e独立地为F、Cl、Br、I、N 3、C 1-C 20的烷基。
在本发明某些优选实施方案中，所述的如式C所示的3，3-二氟烯丙基鎓盐中的某些基团如下定义，未提及的基团同本申请任一方案所述(以下简称，“在本发明的某一方案中”)，其中，
X为常规的阴离子，例如可为本领域常见的有机或者无机阴离子，例如三氟甲磺酸阴离子、氟硼酸阴离子、六氟磷酸阴离子、六氟锑酸阴离子、对甲苯磺酸阴离子、氟阴离子、氯阴离子、溴阴离子、碘阴离子等。
X为常规的阴离子，例如可为本领域常见的有机或者无机阴离子，例如四苯硼酸阴离子、三氟甲磺酸阴离子、氟硼酸阴离子、六氟磷酸阴离子、六氟锑酸阴离子、对甲苯磺酸阴离子、氟阴离子、氯阴离子、溴阴离子、碘阴离子等。
在本发明的某一方案中，如上任一所述的C 1-C 20的烷基、被取代的C 1-C 20的烷基里的C 1-C 20的烷基独立地为C 1-C 10的烷基，又如C 1-C 6的烷基，还如甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、正己基(n-C 6H 13)或叔丁基。
在本发明的某一方案中，如上任一所述的C 1-C 20的烷基、被取代的C 1-C 20的烷基里的C 1-C 20的烷基独立地为C 1-C 10的烷基，又如C 1-C 6的烷基，还如甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基。
在本发明的某一方案中，如上任一所述的C 2-C 20的炔基、被取代的C 2-C 20的炔基里的C 2-C 20的炔基独立地为C 2-C 10的炔基，又如C 2-C 6的炔基，还如
Figure PCTCN2022115642-appb-000003
在本发明的某一方案中，如上任一所述的C 2-C 20的烯基、被取代的C 2-C 20的烯基里的C 2-C 20的烯基独立地为C 2-C 10的烯基，又如C 2-C 6的烯基，还如
Figure PCTCN2022115642-appb-000004
在本发明的某一方案中，如上任一所述的C 1-C 20的杂烷基、被取代的C 1-C 20的杂烷基里的C 1-C 20的杂烷基独立地为-C(＝O)O-杂化的C 1-C 20的烷基；例如-C(＝O)OMe。
在本发明的某一方案中，如上任一所述的C 1-C 20的杂烷基、被取代的C 1-C 20的杂烷基里的C 1-C 20的杂烷基独立地为-C(＝O)O-或-O-杂化的C 1-C 20的烷基；例如-C(＝O)OMe、-C(＝O)OEt、-OCH 3。
在本发明的某一方案中，如上任一所述的C 6-C 20的芳基、被取代的C 6-C 20的芳基里的C 6-C 20的芳基独立地为苯基。
在本发明的某一方案中，如上任一所述的R 1和R 4与相连的Z一起形成：5-20元的杂环烷基、被 取代的5-20元的杂环烷基里的5-20元的杂环烷基独立地为5-10元的杂环烷基，例如
Figure PCTCN2022115642-appb-000005
Figure PCTCN2022115642-appb-000006
在本发明的某一方案中，如上任一所述的R 1和R 4与相连的Z一起形成：5-20元的杂芳基、被取代的5-20元的杂芳基里的5-20元的杂芳基独立地为5-10元的杂芳基，例如苯并噻吩
Figure PCTCN2022115642-appb-000007
在本发明的某一方案中，如上任一所述的C 3-C 20的环烷基独立地为环丙基、环丁基、环戊基或环己基。
在本发明的某一方案中，所述R 4独立地为C 1-C 20的烷基，优选C 1-C 6的烷基，例如甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基。
在本发明的某一方案中，R 1、R 2、R 3和R 4独立地为H、F、Cl、Br、Me、Et、苯基(ph)、甲苯基(Tol)、甲氧基苯基、溴代苯基、三(甲基)苯基(例如2,4,6-三甲苯基Mes)、三(异丙基)苯基(TIPP)、苯基亚乙基、叔丁基苯基、正己基、-C(＝O)OMe、
Figure PCTCN2022115642-appb-000008
Figure PCTCN2022115642-appb-000009
在本发明的某一方案中，R 1、R 2、R 3和R 4独立地为H、F、Cl、Br、Me、Et、苯基(ph)、甲苯基(Tol)、甲氧基苯基、溴代苯基、三(甲基)苯基(例如2,4,6-三甲苯基Mes)、三(异丙基)苯基(TIPP)、苯基亚乙基、-C(＝O)OMe、
Figure PCTCN2022115642-appb-000010
在本发明的某一方案中，R 2独立地为H、Me、正己基、-C(＝O)OMe、
Figure PCTCN2022115642-appb-000011
Figure PCTCN2022115642-appb-000012
在本发明的某一方案中，R 2独立地为H、Me、-C(＝O)OMe、
Figure PCTCN2022115642-appb-000013
在本发明的某一方案中，R 4独立地为Me或Et。
在本发明的某一方案中，R 3独立地为H、F、Cl、Br、-C(＝O)OMe、Me、苯基、苯基亚乙基、甲氧基苯基、叔丁基苯基、
Figure PCTCN2022115642-appb-000014
在本发明的某一方案中，R 3独立地为H、F、Cl、Br、-C(＝O)OMe、Me、苯基、苯基亚乙基、
Figure PCTCN2022115642-appb-000015
在本发明的某一方案中，R 1和R 4中的一个为Me或Et，另一个为苯基、甲苯基、甲氧基苯基、溴代苯基、三(甲基)苯基、三(异丙基)苯基、苯基亚乙基。
在本发明的某一方案中，R 1和R 4与相连的Z一起形成：
Figure PCTCN2022115642-appb-000016
Figure PCTCN2022115642-appb-000017
Alkyl独立地为所述的C 1-C 20的烷基、被一个或多个R 5取代的C 1-C 20的烷基；例如
Figure PCTCN2022115642-appb-000018
在本发明的某一方案中，所述的如式C所示的3，3-二氟烯丙基鎓盐为如下任一结构：
Figure PCTCN2022115642-appb-000019
Figure PCTCN2022115642-appb-000020
其中，X的定义如上所述；X为F、Cl、Br、BF 4、OTf、BPh 4、PF 6、TeF 6或SbF 6，TIPP为三(异丙基)苯基，Mes为2,4,6-三甲苯基，Tol为甲苯基，Alkyl独立地为所述的C 1-C 20的烷基、被一个或多个R 5取代的C 1-C 20的烷基；Ar独立地为所述的C 6-C 20的芳基、被一个或多个R 7取代的C 6-C 20的芳基；R 5与R 7的定义如本发明所述。
在本发明的某一方案中，所述的如式C所示的3，3-二氟烯丙基鎓盐为如下任一化合物：
Figure PCTCN2022115642-appb-000021
Figure PCTCN2022115642-appb-000022
本发明提供了一种如式C所示的3，3-二氟烯丙基鎓盐类化合物的制备方法，其包含如下步骤：
在有机溶剂中，将如式D所示的化合物与烷基化试剂进行烷基化反应，得到如式C所示的3，3-二氟烯丙基鎓盐类化合物，即可；所述烷基化试剂为R 4X和/或R 4I与AgX的体系或R 4 3OBF 4；
Figure PCTCN2022115642-appb-000023
其中，Z、X、R 1、R 2、R 3和R 4的定义如上任一方案所示。
所述的烷基化反应中，所述烷基化试剂可为R 4X，例如MeOTf。
所述的烷基化反应中，所述烷基化试剂可为(R 4) 3OBF 4，例如(Et) 3OBF 4。
所述的烷基化反应的操作和条件为本领域该类反应中常规的操作和条件；本发明中优选如下，
所述的烷基化反应中，所述的有机溶剂可为非质子溶剂，如DCM、THF，DMF或DMSO。
所述的烷基化反应中，所述的有机溶剂的用量可不做具体限定，以不影响反应即可；本发明中，所述的如式D所示的化合物与所述的有机溶剂的质量体积比较佳地为0.01mol/L～2mol/L(例如0.7mol/L～1mol/L)。
所述的烷基化反应中，所述的如式D所示的化合物与烷基化试剂的摩尔比可为1:0.8至1:1.5，例如1:0.9、1:1、1.12：1、1.15:1、1：0.933或1：1.1。
所述的烷基化反应中，所述的如式D所示的化合物与烷基化试剂的摩尔比可为1:0.9至1:1.5，例如1:1、1.15:1。
所述的烷基化反应较佳地在氩气或氮气下进行。
所述的烷基化反应较佳地在0℃至140℃下进行，例如10至30℃。
所述的烷基化反应中，所述的反应的进程可以采用本领域中的常规监测方法(例如TLC或NMR)进行监测，一般以所述的如式D所示化合物消失或不再反应时为反应终点。
在某一方案中，所述的制备方法还包括所述如式D所示的化合物的制备方法，其包括如下步骤：在有机溶剂中，将如式A所示化合物和如式B所示的化合物进行如下式所示的取代反应，所得所述的如式D所示的化合物，即可；
Figure PCTCN2022115642-appb-000024
其中，Z、R 1、R 2和R 3的定义如上任一方案所示；
X 1为F、Cl或Br；M 1为碱金属。
在某一方案中，所述的取代反应中，M 1为Na、K或Li。
所述的取代反应中，所述的取代反应的操作和条件可为本领域该类反应中常规的操作和条件；本发明中优选如下，
所述的取代反应中，所述的有机溶剂可为非质子溶剂，如二氧六环(二氧六环)、四氢呋喃(THF)，N,N-二甲基甲酰胺(DMF)和二甲基亚砜(DMSO)中的一种或多种。
所述的取代反应中，所述的有机溶剂的用量可不做具体限定，以不影响反应即可；本发明中，所述的如式B所示的化合物与所述的有机溶剂的质量体积比较佳地为0.01mol/L～2mol/L(例如0.7mol/L～1mol/L)。
所述的取代反应中，所述的如式B所示化合物可使用常规的溶液形式加入，例如THF溶液中，又例如1.2M的THF溶液。
所述的取代反应中，所述的如式A所示的化合物与如式B所示的化合物的摩尔比可为1:1至1:3，例如1:1.2、1:1.25、1:2、1:1.67、1:1.335。
所述的取代反应中，所述的如式A所示的化合物与如式B所示的化合物的摩尔比可为1:1至1:3，例如1:1.2、1:1.25、1:2。
所述的取代反应较佳地在氩气或氮气下进行。
所述的取代反应较佳地在室温至140℃下进行，优选为50℃至140℃下进行，例如100±10℃。
所述的取代反应中，所述的反应的进程可以采用本领域中的常规监测方法(例如TLC或NMR)进行监测，一般以所述的如式A所示化合物消失或不再反应时为反应终点。
本发明还提供了一种如上式C所示的3，3-二氟烯丙基鎓盐类化合物作为α,α-偕二氟烯丙基化试剂的应用。
本发明中，通过所述的式C所示的3，3-二氟烯丙基鎓盐类化合物中R 1或R 4的位阻和电性效应可以调节其反应选择性。
在某一方案中，所述的应用包括如下步骤：
在溶剂中，将如式C所示的3，3-二氟烯丙基鎓盐类化合物与锌试剂进行如下所示的偶联反应，得到如式E所示的α,α-偕二氟烯丙基类化合物，即可；
Figure PCTCN2022115642-appb-000025
其中，Z、X、R 1、R 2、R 3和R 4的定义如上任一方案所示；
[C]表示通过Csp1、Csp2或Csp3与[Zn]连接的部分；[Zn]表示ZnX 2、Zn·LiX 2、ZnX 2·LiX 2；X 2独立地为溴或氯。
在某一方案中，所述的偶联反应中，所述[Zn]为ZnBr、ZnCl、Zn·LiCl、ZnCl·LiCl、ZnBr·LiCl。
所述的偶联反应的操作和条件可为本领域该类反应中常规的操作和条件。本发明中可优选如下：
所述的偶联反应中，所述的溶剂可为醚类溶剂；所述的醚类溶剂为四氢呋喃。
所述的偶联反应中，所述的有机溶剂的用量可不做具体限定，以不影响反应即可；本发明中，所述的如式C所示化合物与所述的有机溶剂的质量体积比较佳地为0.01mol/L～2mol/L(例如0.1mol/L)。
所述的偶联反应中，所述的锌试剂可使用常规的溶液形式加入，例如二甲基乙酰胺(DMA)和/或THF溶液中，又例如0.1至1M的DMA和/或THF溶液。
所述的偶联反应中，所述的式C所示的3，3-二氟烯丙基鎓盐类化合物与锌试剂的摩尔比可为1:1至1.5；例如1:1.1、1:1.2、1:1.3。
所述的偶联反应在催化剂存在下进行，所述的催化剂可为卤化亚铜，例如CuBr；所述的催化剂的与所述的式C所示的3，3-二氟烯丙基鎓盐类化合物的摩尔比可为0.2至0.005；例如0.01、0.025、0.05、0.1。
所述的偶联反应的温度可为-78至35℃，例如室温下进行。
所述的反应的进程可以采用本领域中的常规监测方法(例如TLC或NMR)进行监测，一般以所述的如式C所示化合物消失或不再反应时为反应终点。
在某一方案中，所述的如式C所示的3，3-二氟烯丙基鎓盐类化合物为
Figure PCTCN2022115642-appb-000026
Figure PCTCN2022115642-appb-000027
在某一方案中，所述应用中，所述的锌试剂与相应的如式E所示的α,α-偕二氟烯丙基类化合物为如下的任一组：
Figure PCTCN2022115642-appb-000028
Figure PCTCN2022115642-appb-000029
Figure PCTCN2022115642-appb-000030
Figure PCTCN2022115642-appb-000031
Figure PCTCN2022115642-appb-000032
Figure PCTCN2022115642-appb-000033
Figure PCTCN2022115642-appb-000034
本专利所述的鎓盐均能与上述常规的锌试剂在铜盐催化下实现α,α-偕二氟烯丙基化反应得到预期的含α,α-偕二氟烯丙基的结构。
除非另有规定，本文使用的所有技术术语和科学术语具有要求保护主题所属领域的标准含义。倘若对于某术语存在多个定义，则以本文定义为准。
基团定义
除非另外说明，应当应用本文所使用的下列定义。出于本发明的目的，化学元素与元素周期表CAS版，和《化学和物理手册》，第75版，1994一致。此外，有机化学一般原理可参考"Organic Chemistry",Thomas Sorrell,University Science Books,Sausalito:1999,和"March's Advanced Organic Chemistry”by Michael B.Smith and Jerry March,John Wiley&Sons,New York:2007中的描述，其全部内容通过引用并入本文。
在本说明书中，可由本领域技术人员选择基团及其取代基以提供稳定的结构部分和化合物。当通过从左向右书写的常规化学式描述取代基时，该取代基也同样包括从右向左书写结构式时所得到的在化学上等同的取代基。
在本文中定义的某些化学基团前面通过简化符号来表示该基团中存在的碳原子总数。例如，C 1-C 6烷基是指具有总共1、2、3、4、5或6个碳原子的如下文所定义的烷基。简化符号中的碳原子总数不包括可能存在于所述基团的取代基中的碳。
在本文中，取代基中定义的数值范围如0至4、1-4、1至3等表明该范围内的整数，如1-6为1、2、3、4、5、6。
除前述以外，当用于本申请的说明书及权利要求书中时，除非另外特别指明，否则以下术语具有如下所示的含义。
术语“包括”为开放式表达，即包括本发明所指明的内容，但并不排除其他方面的内容。
术语“被取代的”是指特定原子上的任意一个或多个氢原子被取代基取代，只要特定原子的价态是正常的并且取代后的化合物是稳定的。
一般而言，术语“取代的”表示所给结构中的一个或多个氢原子被具体取代基所取代。进一步地，当该基团被1个以上所述取代基取代时，所述取代基之间是相互独立，即，所述的1个以上的取代基可以是互不相同的，也可以是相同的。除非其他方面表明，一个取代基团可以在被取代基团的各个可取代的位置进行取代。当所给出的结构式中不只一个位置能被选自具体基团的一个或多个取代基所取代，那么取代基可以相同或不同地在各个位置取代。
在本说明书的各部分，本发明公开化合物的取代基按照基团种类或范围公开。特别指出，本发明包括这些基团种类和范围的各个成员的每一个独立的次级组合。术语“C x-C y烷基"是指含有x至y个碳原子的直链或支链饱和烃。例如，术语“C 1～C 6烷基”或“C 1-6烷基”特别指独立公开的甲基、乙基、C 3烷基、C 4烷基、C 5烷基和C 6烷基；“C 1-4烷基”特指独立公开的甲基、乙基、C 3烷基(即丙基，包括正丙基和异丙基)、C 4烷基(即丁基，包括正丁基、异丁基、仲丁基和叔丁基)。
本文所用术语“部分”、“结构部分”、“化学部分”、“基团”、“化学基团”是指分子中的特定片段或官 能团。化学部分通常被认为是嵌入或附加到分子上的化学实体。
当所列举的取代基中没有指明其通过哪一个原子连接到化学结构通式(包括但未具体提及的化合物)中时，这种取代基可以通过其任何原子相键合。取代基和/或其变体的组合只有在这样的组合会产生稳定的化合物的情况下才是被允许的。
当任意变量(例如R 1a)在化合物的定义中多次出现时，该变量每一位置出现的定义与其余位置出现的定义无关，它们的含义互相独立、互不影响。因此，若某基团被1个、2个或3个R 1a基团取代，也就是说，该基团可能会被最多3个R 1a取代，该位置R 1a的定义与其余位置R 1a的定义是互相独立的。另外，取代基及/或变量的组合只有在该组合产生稳定的化合物时才被允许。
当所列举的基团中没有明确指明其具有取代基时，这种基团仅指未被取代。例如当“C 1-C 4烷基”前没有“取代或未取代的”限定时，仅指“C 1-C 4烷基”本身或“未取代的C 1-C 4烷基”。
在本发明的各部分，描述了连接取代基。当该结构清楚地需要连接基团时，针对该基团所列举的马库什变量应理解为连接基团。例如，如果该结构需要连接基团并且针对该变量的马库什基团定义列举了“烷基”，则应该理解，该“烷基”代表连接的亚烷基基团。
在一些具体的结构中，当烷基基团清楚地表示为连接基团时，则该烷基基团代表连接的亚烷基基团，例如，基团“卤代-C 1-C 6烷基”中的C 1-C 6烷基应当理解为C 1-C 6亚烷基。
术语“卤素”是指氟、氯、溴或碘，尤其指F或Cl。
在本申请中，作为基团或是其它基团的一部分(例如用在卤代烷基、氘代烷基等基团中)，术语“烷基”是指包括具有指定碳原子数目的支链和直链的饱和脂族烃基，仅由碳原子和氢原子组成，且通过单键与分子的其余部分连接。例如具有1至20个(优选1至10个，更优选1至6个，更优选1至4个)碳原子。其中，丙基为C 3烷基(包括同分异构体，例如正丙基或异丙基)；丁基为C 4烷基(包括同分异构体，例如正丁基、仲丁基、异丁基或叔丁基)；戊基为C 5烷基(包括同分异构体，例如正戊基、1-甲基-丁基、1-乙基-丙基、2-甲基-1-丁基、3-甲基-1-丁基、异戊基、叔戊基或新戊基)；己基为C 6烷基(包括同分异构体，例如正己基、1-乙基-2-甲基丙基、1，1，2-三甲基丙基、1，1-二甲基丁基、1，2-二甲基丁基、2，2-二甲基丁基、1，3-二甲基丁基、2-乙基丁基、2-甲基戊基、3-甲基戊基、4-甲基戊基、2，3-二甲基丁基)。例如包括但不限于甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、2-甲基丁基、2,2-二甲基丙基、正己基、正庚基、2-甲基己基、3-甲基己基、正辛基、壬基和癸基等其类似烷基。
在本申请中，作为基团或是其它基团的一部分，术语“亚烷基”表示从饱和的直链或支链烃基中去掉两个氢原子所得到的饱和的二价烃基基团；即烷基中的一个氢被取代，烷基的定义如上所述。亚烷基基团的实例包括亚甲基(-CH 2-)，亚乙基{包括-CH 2CH 2-或-CH(CH 3)-}，亚异丙基{包括-CH(CH 3)CH 2-或-C(CH 3) 2-}等等。
在本申请中，作为基团或是其它基团的一部分(例如用在卤代烷基、氘代烷基等基团中)，术语“杂烷基”是指烷基中可以存在含O、S、N(以叔胺部分的形式)、B、P或Si的杂原子或杂原子团(例如 C(＝O)、S(＝O)、S(＝O) 2、
Figure PCTCN2022115642-appb-000035
P(＝O)、P(＝O) 2、
Figure PCTCN2022115642-appb-000036
a端表示连接位置)，以提供杂烷基(例如，包含一个或多个醚、硫醚或氨基键的烷基)。例如烷氧基、烷硫基等；杂烷基的说明性实例包括-C(＝O)OMe和-CH 2CH 2OCH 2CH 3。
在本申请中，作为基团或是其它基团的一部分，术语“烷氧基”是指-O-烷基，烷基的定义如上所述。
在本申请中，作为基团或是其它基团的一部分，术语“烷硫基”是指-S-烷基，烷基的定义如上所述。
在本申请中，作为基团或是其它基团的一部分，术语“烯基”是指具有至少一个双键的直链或支链的烃链基，仅由碳原子和氢原子组成、且通过单键与分子的其余部分连接。例如具有2至20个(优选2至10个，更优选2至6个，最优选2至4个)碳原子，例如包括但不限于乙烯基、正丙烯基、异丙烯基、正丁烯基、异丁烯基、仲丁烯基、叔丁烯基、正戊烯基、2-甲基丁烯基、2,2-二甲基丙烯基、正己烯基、庚烯基、2-甲基己烯基、3-甲基己烯基、辛烯基、壬烯基和癸烯基等。
在本申请中，作为基团或是其它基团的一部分，术语“环烷基”意指饱和的单环或多环(例如双环、三环或更多环的桥环、并环(稠环)或螺环体系)的碳环取代基，且其可经由任何适宜的碳原子通过单键与分子的其余部分连接。例如具有3至20个碳原子的3-20元环烷基，优选具有3至10个碳原子的3-10元环烷基，更优选具有3至7个碳原子的3-7元环烷基，最优选具有3至6个碳原子的3-6元环烷基。在某一方案中，典型的单环环烷基，如环丙基、环丁基、环戊基、环己基或环庚基。
在本申请中，作为基团或是其它基团的一部分，术语“杂环烷基”是指具有由碳原子以及1个或多个选自O、S、N(以叔胺部分的形式)、B、P或Si的杂原子或杂原子团(例如C(＝O)、S(＝O)、S(＝O) 2、
Figure PCTCN2022115642-appb-000037
P(＝O)、P(＝O) 2、
Figure PCTCN2022115642-appb-000038
a端表示连接位置)组成的稳定的饱和的杂环烃基。例如由2至20个(优选2至6个)碳原子以及1至6个选自C(＝O)、S、S(＝O)、S(＝O) 2、O、N、Si、P、P(＝O)、P(＝O) 2和B的杂原子或杂原子基团组成的稳定的3至26元(优选3至20元，更优选4至10元，最优选3至7元)的饱和的杂环烃基；优选含有1个、2个或3个独立选自N、O和S的环杂原子的4-10元饱和的单环或多环(例如双环、三环或更多环的桥环、并环(稠环)或螺环体系)的杂环烃基。杂环烷基二环的环系统可以在一个或两个环中包括一个或多个杂原子；并且是饱和的。在一些实施例中，“杂环烷基”是5至7元单环的杂环烷基、6至8元并环连接的杂环烷基、6至8元桥环连接的杂环烷基或7至10元螺环连接的杂环烷基。
在本申请中，作为基团或是其它基团的一部分，术语“芳基”意指满足4n+2规则的共轭烃环体系基团。例如具有6至20个碳原子(优选具有6至10个碳原子)的满足4n+2规则的共轭烃环体系基团。就本发明的目的而言，芳基可以为单环、双环、三环或更多环的环体系，还可以与上文所定义的环烷基、环烯基、杂环烷基或杂环烯基稠合，条件是芳基经由芳香环上的原子通过单键与分子的其余部分 连接。在某一方案中，术语“芳基”是指由碳原子组成的芳香基团，每个环均具有芳香性。芳基的实例包括但不限于苯基、萘基。
在本申请中，作为基团或是其它基团的一部分，术语“杂芳基”意指环内具有碳原子和杂原子和杂原子团选自O、S、N(以叔胺部分的形式)、B、P或Si的杂原子或杂原子团(例如C(＝O)、S(＝O)、S(＝O) 2、
Figure PCTCN2022115642-appb-000039
P(＝O)、P(＝O) 2、
Figure PCTCN2022115642-appb-000040
a端表示连接位置)的共轭环系基团。例如环内具有1至20个碳原子(优选具有1至10个碳原子)和1至6个杂原子和杂原子团选自C(＝O)、S、S(＝O)、S(＝O) 2、O、N、Si、P、P(＝O)、P(＝O) 2和B的5至26元共轭环系基团。除非本说明书中另外特别指明，否则杂芳基可为单环、双环、三环或更多环的环体系，还可以与上文所定义的环烷基、环烯基、杂环烷基或杂环烯基稠合，条件是杂芳基经由芳香环上的原子通过单键与分子的其余部分连接。就本发明的目的而言，杂芳基优选包含1至5个选自氮、氧和硫的杂原子的稳定的5至20元芳香性基团，进一步优选包含1至5个选自氮、氧和硫的杂原子的稳定的5至10元芳香性基团。在某一方案中，术语“杂芳基”是指含有杂原子的芳香基团，每个环均具有芳香性；优选含有1个、2个或3个独立选自氮、氧和硫的杂原子的芳族5-6元单环或9-10元双环。
应该理解，在本发明中使用的单数形式，如“一种”，包括复数指代，除非另有规定。
术语“一种(个)或多种(个)”或“一种(个)或两种(个)以上”是指即1、2、3、4、5、6、7、8、9或更多。
除非另有说明，本发明采用质谱、元素分析的传统方法，各步骤和条件可参照本领域常规的操作步骤和条件。
除非另有指明，本发明采用分析化学、有机合成化学和光学的标准命名及标准实验室步骤和技术。在某些情况下，标准技术被用于化学合成、化学分析、发光器件性能检测。
另外，需要说明的是，除非以其他方式明确指出，在本发明中所采用的描述方式“…独立地为”应做广义理解，是指所描述的各个个体之间是相互独立的，可以独立地为相同或不同的具体基团。更详细地，描述方式“…独立地为”既可以是指在不同基团中，相同符号之间所表达的具体选项之间互相不影响；也可以表示在相同的基团中，相同符号之间所表达的具体选项之间互相不影响。
本领域技术人员可以理解，根据本领域中使用的惯例，本申请描述基团的结构式中所使用的
Figure PCTCN2022115642-appb-000041
及
Figure PCTCN2022115642-appb-000042
是指，相应的基团R通过该位点与化合物中的其它片段、基团进行连接。
本领域技术人员可以理解，根据本领域中使用的惯例，本申请描述基团的结构式中所使用的
Figure PCTCN2022115642-appb-000043
表示单键或双键。
除非另有规定，本文使用的所有技术术语和科学术语具有要求保护主题所属领域的标准含义。倘若对于某术语存在多个定义，则以本文定义为准。
在不违背本领域常识的基础上，上述各优选条件，可任意组合，即得本发明各较佳实例。
本发明所用试剂和原料均市售可得。
本发明的积极进步效果在于：本发明提供的如式C所示的3，3-二氟烯丙基鎓盐，可作为α,α-偕二氟烯丙基化试剂，为α,α-偕二氟烯丙基化提供了更加广谱和廉价的新方法，其效率高，应用前景较佳。
具体实施方式
下面通过实施例的方式进一步说明本发明，但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法，按照常规方法和条件，或按照商品说明书选择。
本发明中，室温(RT或rt指室温)指环境温度，为10℃-35℃。过夜是指8-15小时。回流是指常压下溶剂回流温度。本申请中所用锌试剂、硫醚可采用本领域常规方法制得也可采用本申请中所记载的方法制备得到。本申请所述无水无氧条件，如无特殊说明，指在保护性气体下进行反应，例如在氩气(Argon或Ar指氩气)中进行反应。本申请中温度以摄氏度(℃)为单位，具体地表述为“℃”、“摄氏度”或“度”。
实施例1
Figure PCTCN2022115642-appb-000044
无水无氧下，向100mL三颈瓶中加入钠氢(130mmol，5.2g)，Ar保护下加入250ml的1，4-二氧六环(Dioxane指1，4二氧六环或二氧六环)，反应体系置于冰水浴中，将硫酚(100mmol，12.4g)配置成二氧六环溶液，缓慢滴加入反应体系(体系结块)，然后将反应体系放入超声20min，之后再置于冰水浴中，迅速加入溴二氟丙烯(13.6ml)，缓慢恢复室温反应1h。所得反应液加入饱和氯化铵淬灭，加至反应体系中白色固体消失，然后旋蒸除去二氧六环，剩余液体用乙醚萃取三次，合并乙醚相，旋干，过柱子。纯PE柱层析得黄色液体16.13g，产率80.6％。 1H NMR(400MHz,CDCl3)δ7.29(d,J＝8.2Hz,2H),7.12(d,J＝8.2Hz,2H),4.35(dtd,J＝24.0,8.4,1.6Hz,1H),3.45(dt,J＝8.4,1.6Hz,2H),2.33(s,3H). 19F NMR(376MHz,CDCl3)δ-86.63(d,J＝38.9Hz,1F),-88.68(ddt,J＝39.0,24.0,1.6Hz,1F). 13C NMR(126MHz,CDCl3)δ157.1(dd,J＝290.1,288.8Hz),137.2,131.4,130.9,129.7,76.4(dd,J＝24.7,19.0Hz),28.0(d,J＝6.1Hz),21.0.MS(EI):m/z(％)77,123,200(100)([M]+).HRMS(EI)m/z:([M]+)Calculated for C10H10F2S:200.0466；Found:200.0470.
实施例2
Figure PCTCN2022115642-appb-000045
无水无氧下，向300mL反应釜加入氢氧化钠(52.5mmol，2.1g)，将硫酚(50mmol，6.21g)配置成二氧六环溶液，缓慢滴加入反应体系，之后再置于冰水浴中，重新抽换气，氩气(Ar)下迅速加入三氟丙烯成二氧六环溶液(1.0M,150mL)，120度下反应15小时。加入饱和氯化铵淬灭，加至反 应体系中白色固体消失，然后旋蒸除去二氧六环，剩余液体用乙醚萃取三次，合并乙醚相，旋干，纯PE柱层析得产物8.18g，纯度89％，产率72％。
实施例3
Figure PCTCN2022115642-appb-000046
无水无氧下，向100mL圆底瓶中加入硫醚(100mmol，20.25g,1.12equiv)，加入超干的二氯甲烷(DCM)25ml，然后加入三氟甲烷磺酸甲酯(MeOTf，9.3ml，89mmol，1.0equiv)，室温(rt、RT指室温)反应过夜。滴加乙醚至有固体析出，继续加乙醚，搅拌，过滤，乙醚洗三次，得产物，白色固体31.35g，产率97.4％。 1H NMR(400MHz,Chloroform-d)δ7.83(d,J＝6.3Hz,2H),7.48(d,J＝7.8Hz,2H),4.67–4.35(m,3H),3.39(s,3H),2.48(s,3H). 13C NMR(101MHz,Chloroform-d)δ162.55–156.34(m),135.08,131.22,130.85,122.06,68.65(dd,J＝31.8,17.3Hz),42.11(d,J＝8.1Hz),25.21.MS(EI):m/z(％)153.1(100),215.1(M +).HRMS:Calculated for C 10H 13F 2S:215.0701；Found:215.0702.
实施例4
Figure PCTCN2022115642-appb-000047
无水无氧下，向100mL三颈瓶中加入二苯二硫醚(8.8g，40mmol)抽换气三次，氩气(Ar)下加入30mL超干正己烷(Hexane)，置于室温(RT表示室温)水浴中，然后，注射器滴加正丁基锂(16.0mL,2.5M的正己烷(Hexane)溶液,40mmol)，(有大量白色固体生成，反应放热，待反应瓶温度降至室温即可停止反应)。反应结束，加入乙醚稀释，直接在通风橱过滤，乙醚洗涤三次，然后将固体转至100mL史莱克瓶，抽干，加入20mL四氢呋喃(简述为THF)，搅拌(固体完全溶解)，置于室温水浴中，快速加入溴二氟丙烯(7.85g,50mmol)搅拌反应过夜，加水淬灭，旋掉THF，乙醚萃取三次，合并干燥旋干，柱层析得3.86g，淡黄色液体，产率52％。
实施例5
Figure PCTCN2022115642-appb-000048
无水无氧下，向100mL三颈瓶中加入二苯二硒醚(12.49g，40mmol)抽换气三次，Ar下加入30mL超干正己烷，置于室温(RT)水浴中，然后，注射器滴加正丁基锂(16.0mL,2.5M的正己烷溶液,40mmol)，(有大量白色固体生成，反应放热，待反应瓶温度降至室温即可停止反应)。反应结束，加入乙醚稀释，直接在通风橱过滤，乙醚洗涤三次，然后将固体转至100mL史莱克瓶，抽干，加入20mL THF，搅拌(固体完全溶解)，置于室温水浴中，快速加入溴二氟丙烯(7.85g,50mmol)搅拌反应过夜，加水淬灭，旋掉THF，乙醚萃取三次，合并干燥旋干，柱层析得5.0g，产率54％。
实施例6
Figure PCTCN2022115642-appb-000049
无水无氧下，向100mL三颈瓶中加入二苯二碲醚(16.4g，40mmol)抽换气三次，Ar下加入30mL超干正己烷，置于室温水浴中，然后，注射器滴加正丁基锂(16.0mL,2.5M的正己烷溶液,40mmol)，(有大量白色固体生成，反应放热，待反应瓶温度降至室温即可停止反应)。反应结束，加入乙醚稀释，直接在通风橱过滤，乙醚洗涤三次，然后将固体转至100mL史莱克瓶，抽干，加入20mL THF，搅拌(固体完全溶解)，置于室温水浴中，快速加入溴二氟丙烯(7.85g,50mmol)搅拌反应过夜，加水淬灭，旋掉THF，乙醚萃取三次，合并干燥旋干，柱层析得6.54g，产率58％。
实施例7
Figure PCTCN2022115642-appb-000050
无水无氧下，向100mL三颈瓶中加入二苯二硒醚(12.49g，40mmol)抽换气三次，Ar下加入30mL超干正己烷，置于室温水浴中，然后，注射器滴加正丁基锂(16.0mL,2.5M的正己烷溶液,40mmol)，(有大量白色固体生成，反应放热，待反应瓶温度降至室温即可停止反应)。反应结束，加入乙醚稀释，直接在通风橱过滤，乙醚洗涤三次，然后将固体转至100mL封管，抽干，加入20mL二氧六环，搅拌(固体完全溶解)，置于室温水浴中，快速加入三氟丙烯THF溶液(1.2M,12.5mL)，100度下反应五小时。加入饱和氯化铵淬灭，加至反应体系中白色固体消失，然后旋蒸除去二氧六环，剩余液体用乙醚萃取三次，合并乙醚相，旋干，纯PE柱层析得产物4.44g，产率48％。
实施例8
Figure PCTCN2022115642-appb-000051
无水无氧下，向100mL三颈瓶中加入二苯二碲醚(16.4g，40mmol)抽换气三次，Ar下加入30mL超干正己烷，置于室温水浴中，然后，注射器滴加正丁基锂(16.0mL,2.5M的正己烷溶液,40mmol)，(有大量白色固体生成，反应放热，待反应瓶温度降至室温即可停止反应)。反应结束，加入乙醚稀释，直接在通风橱过滤，乙醚洗涤三次，然后将固体转至100mL封管，抽干，加入20mL二氧六环，搅拌(固体完全溶解)，置于室温水浴中，快速加入三氟丙烯THF溶液(1.2M，12.5mL)，100度下反应五小时。加入饱和氯化铵淬灭，加至反应体系中白色固体消失，然后旋蒸除去二氧六环，剩余液体用乙醚萃取三次，合并乙醚相，旋干，纯PE柱层析得产物5.45g，产率45％。
实施例9
Figure PCTCN2022115642-appb-000052
无水无氧下，向100mL三颈瓶中加入硫醚(6.7mmol，1.25g,1.1equiv)，加入超干的DCM(10ml)，然后冰水浴下加入MeOTf(0.62ml，6.1mmol,1.0equiv)，自然升至室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得1.69g，粘稠液体. 1H NMR(400MHz,Chloroform-d)δ7.96(d,J＝7.9Hz,2H),7.75(t,J＝7.4Hz,1H),7.66(t,J＝7.7Hz,2H),4.60–4.39(m,3H),3.38(s,3H). 19F NMR(376MHz,Chloroform-d)δ-75.98(d,J＝14.1Hz),-78.56(s),-79.09(dd,J＝20.7,14.2Hz). 13C NMR(101MHz,Chloroform-d)δ162.55–156.34(m),135.08,131.22,130.85,122.06,68.65(dd,J＝31.8,17.3Hz),42.11(d,J＝8.1Hz),25.21.MS(EI):m/z(％)201.1(100),243.1(M +).HRMS:Calculated for C 10H 11F 2S:201.0544；Found:201.0544。
实施例10
Figure PCTCN2022115642-appb-000053
无水无氧下，向100mL三颈瓶中加入硒醚(7mmol，1.63g,1.15equiv)，加入超干的DCM(10ml)，然后冰水浴下加入MeOTf(0.62ml，6.1mmol，1.0equiv)，自然升至室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得2.20g目标产物。
实施例11
Figure PCTCN2022115642-appb-000054
无水无氧下，向100mL三颈瓶中加入碲醚(7mmol，1.97g,1.15equiv)，加入超干的DCM(10ml)，然后冰水浴下加入MeOTf(0.62ml，6.1mmol,1.0equiv)，自然升至室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得2.38g目标产物。
实施例12
Figure PCTCN2022115642-appb-000055
无水无氧下，向100mL三颈瓶中加入钠氢(26mmol，1.04g，(60％，分散于液状石蜡))，然后加入超干正己烷(约2.5毫升，淹没固体即可)除去钠氢表面的油，(搅拌两分钟，静置，注射器抽 掉正己烷，重复三次，最后一次抽干)反应体系置于冰水浴中，将硫酚(20mmol，3.0g)配置成二氧六环溶液，缓慢滴加入反应体系(体系结块)，然后塞上塞子放入超声20min，之后再置于冰水浴中，重新抽换气，Ar下迅速加入三氟丙烯THF溶液(1.2M,33.3mL)，100度下反应五小时。加入饱和氯化铵淬灭，加至反应体系中白色固体消失，然后旋蒸除去二氧六环，剩余液体用乙醚萃取三次，合并乙醚相，旋干，纯PE柱层析得产物，产率33.5％。 1H NMR(400MHz,Chloroform-d)δ6.93(s,2H),4.29(dtd,J＝23.9,8.4,1.5Hz,1H),3.22(dt,J＝8.4,1.6Hz,2H),2.50(s,6H),2.27(s,3H). 19F NMR(376MHz,Chloroform-d)δ-86.94(d,J＝37.8Hz),-89.68(dd,J＝39.4,24.1Hz). 13C NMR(101MHz,Chloroform-d)δ155.69(m),143.17,138.57,129.03,128.87,128.63,27.81(d,J＝5.9Hz),21.87,21.41,21.01.MS(EI):m/z(％)151(100),228(M +).HRMS:Calculated for C 10H 13F 2S:228.0779；Found:215.0785。
实施例13
Figure PCTCN2022115642-appb-000056
无水无氧下，向50mL圆底瓶中加入硫醚(6.7mmol，1.53g)，加入超干的DCM(10ml)，然后冰水浴下加入MeOTf(0.64ml,6.4mmol)，自然升至室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得粘稠液体。所得产物柱层析(DCM:MeOH＝10:1)纯化得微黄色油状物。 1H NMR(400MHz,Chloroform-d)δ7.07(s,2H),4.76–4.47(m,3H),3.47(s,3H),2.59(s,6H),2.34(s,3H). 19F NMR(3＝76MHz,Chloroform-d)δ-76.58(d,J＝16.6Hz),-80.12(dd,J＝22.5,17.1Hz). 13C NMR(101MHz,Chloroform-d)δ162.70–155.93(m),146.36,132.40,128.92,114.71,69.62(dd,J＝31.6,17.2Hz),38.98(d,J＝8.1Hz),25.68,21.59,21.26,21.23.MS(EI):m/z(％)243.1(100),315.1(M +).HRMS:Calculated for C 10H 13F 2S:243.1014；Found:243.1015。
实施例14
Figure PCTCN2022115642-appb-000057
无水无氧下，向100mL三颈瓶中加入钠氢(13mmol，0.52g，(60％，分散于液状石蜡))，然后加入超干正己烷(约2.5毫升，淹没固体即可)除去钠氢表面的油，(搅拌两分钟，静置，注射器抽掉正己烷，重复三次，最后一次抽干)反应体系置于冰水浴中，将硫酚(10mmol，2.36g)配置成二氧六环溶液，缓慢滴加入反应体系(体系结块)，然后塞上塞子放入超声20min，之后再置于冰水浴中，重新抽换气，Ar下迅速加入溴二氟丙烯(2.62g,16.7mmol)，100度下反应五小时。加入饱和氯化铵淬灭，加至反应体系中白色固体消失，然后旋蒸除去二氧六环，剩余液体用乙醚萃取三次，合并 乙醚相，旋干，纯PE柱层析得产物，产率36％。 1H NMR(400MHz,Chloroform-d)δ7.01(s,2H),4.33(dt,J＝24.0,8.3Hz,1H),4.00–3.83(m,2H),3.20(d,J＝8.4Hz,2H),2.88(p,J＝7.2Hz,1H),1.24(s,18H). 19F NMR(376MHz,Chloroform-d)δ-86.62(d,J＝38.8Hz),-89.08(dd,J＝38.7,24.0Hz). 13C NMR(101MHz,Chloroform-d)δ160.66–153.89(m),153.27,150.02,127.00,121.81,76.15(dd,J＝24.6,19.4Hz),34.28,31.56,30.10(d,J＝5.9Hz),24.39,23.89.
实施例15
Figure PCTCN2022115642-appb-000058
无水无氧下，向100mL封管中加入钠氢(26mmol，1.04g，(60％，分散于液状石蜡))，然后加入超干正己烷(约2.5毫升，淹没固体即可)除去钠氢表面的油，(搅拌两分钟，静置，注射器抽掉正己烷，重复三次，最后一次抽干)反应体系置于冰水浴中，将硫酚(20mmol，2.8g)配置成二氧六环溶液，缓慢滴加入反应体系(体系结块)，然后塞上塞子放入超声20min，之后再置于冰水浴中，重新抽换气，Ar下迅速加入溴二氟丙烯(4.19g,26.7mmol)，100度下反应五小时。加入饱和氯化铵淬灭，加至反应体系中白色固体消失，然后旋蒸除去二氧六环，剩余液体用乙醚萃取三次，合并乙醚相，旋干，纯PE柱层析得产物3.45g，产率80％。 1H NMR(400MHz,Chloroform-d)δ7.01(s,2H),4.33(dt,J＝24.0,8.3Hz,1H),4.00–3.83(m,2H),3.20(d,J＝8.4Hz,2H),2.88(p,J＝7.2Hz,1H),1.24(s,18H). 19F NMR(376MHz,Chloroform-d)δ-86.62(d,J＝38.8Hz),-89.08(dd,J＝38.7,24.0Hz). 13C NMR(101MHz,Chloroform-d)δ160.66–153.89(m),153.27,150.02,127.00,121.81,76.15(dd,J＝24.6,19.4Hz),34.28,31.56,30.10(d,J＝5.9Hz),24.39,23.89.
实施例16
Figure PCTCN2022115642-appb-000059
无水无氧下(例如在氩气中进行，Argon或Ar指氩气)，向50mL圆底瓶中加入硫醚(1.5mmol，0.32g)，加入超干的DCM(0.5ml)，然后加入MeOTf(0.14ml,1.4mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得0.45g粘稠液体，产率82％。 1H NMR(400MHz,Chloroform-d)δ7.88(d,J＝8.9Hz,2H),7.15(d,J＝9.0Hz,2H),4.69–4.34(m,3H),3.91(s,3H),3.36(s,3H). 19F NMR(376MHz,Chloroform-d)δ-75.88(d,J＝14.3Hz),-78.94–-79.39(m). 13C NMR(101MHz,Chloroform-d)δ162.55–156.34(m),135.08,131.22,130.85,122.06,68.65(dd,J＝31.8,17.3Hz),42.11(d,J＝8.1Hz),25.21.MS(EI):m/z(％)231.1(100),233.1(M +).HRMS:Calculated for C 10H 13F 2S:231.0650；Found:231.0652。
实施例17
Figure PCTCN2022115642-appb-000060
无水无氧下，向50mL圆底瓶中加入钠氢(26mmol，1.04g，(60％，分散于液状石蜡))，然后加入超干正己烷(约2.5毫升，淹没固体即可)除去钠氢表面的油，(搅拌两分钟，静置，注射器抽掉正己烷，重复三次，最后一次抽干)反应体系置于冰水浴中，将硫酚(20mmol，2.8g)配置成二氧六环溶液，缓慢滴加入反应体系(体系结块)，然后塞上塞子放入超声20min，之后再置于冰水浴中，重新抽换气，Ar下迅速加入溴二氟丙烯(4.19g,26.7mmol)，100度下反应五小时。加入饱和氯化铵淬灭，加至反应体系中白色固体消失，然后旋蒸除去二氧六环，剩余液体用乙醚萃取三次，合并乙醚相，旋干，纯PE柱层析得产物3.7g，产率85％。 1H NMR(400MHz,Chloroform-d)δ7.01(s,2H),4.33(dt,J＝24.0,8.3Hz,1H),4.00–3.83(m,2H),3.20(d,J＝8.4Hz,2H),2.88(p,J＝7.2Hz,1H),1.24(s,18H). 19F NMR(376MHz,Chloroform-d)δ-86.62(d,J＝38.8Hz),-89.08(dd,J＝38.7,24.0Hz). 13C NMR(101MHz,Chloroform-d)δ160.66–153.89(m),153.27,150.02,127.00,121.81,76.15(dd,J＝24.6,19.4Hz),34.28,31.56,30.10(d,J＝5.9Hz),24.39,23.89.
实施例18
Figure PCTCN2022115642-appb-000061
无水无氧下，向50mL圆底瓶中加入硫醚(10.7mmol，2.32g)，加入超干的DCM(1.5ml)，然后加入MeOTf(1.03ml,9.75mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得3.9g，粘稠液体，产率92％。 1H NMR(400MHz,Chloroform-d)δ7.86–7.56(m,1H),7.23(t,J＝7.7Hz,1H),7.15(d,J＝8.4Hz,1H),4.68–4.41(m,3H),4.06(s,3H),3.37(s,3H). 19F NMR(376MHz,Chloroform-d)δ-76.12(d,J＝16.2Hz),-78.48,-80.35(dd,J＝23.7,16.3Hz). 13C NMR(101MHz,Chloroform-d)δ162.51–156.50(m),159.42,137.24,132.99,122.67,113.07,107.56,68.90(dd,J＝31.4,17.3Hz),56.79,38.84(d,J＝8.1Hz),23.11.MS(EI):m/z(％)153.1(100),215.1(M +).HRMS:Calculated for C 10H 13F 2S:231.0650；Found:231.0651。
实施例18-1
Figure PCTCN2022115642-appb-000062
无水无氧下，向50mL圆底瓶中加入硫醚(10mmol，2.32g)，加入超干的DCM(15ml)，然后加入三乙基氧鎓四氟硼酸盐(2.09g,11mmol)，室温反应36h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得1.5g，粘稠液体，产率45％。 1H  NMR(400MHz,Chloroform-d)δ7.80–7.72(m,2H),7.27-7.19(m,2H),4.85–4.65(m,2H),4.07(s,3H),3.99-3.83(m，2H),1.36and 1.21(t,J＝8.0Hz,3H). 19F NMR(376MHz,Chloroform-d)δ-76.6and 77.0(d,J＝14.9Hz),-80.5and 80.9(dd,J＝23.7,14.9Hz)，-148.5，-151.4.
实施例19
Figure PCTCN2022115642-appb-000063
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入溴二氟丙烯(25mmol,3.98g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物4.88g,分离产率为92％。 1H NMR(400MHz,Chloroform-d)δ7.87(d,J＝8.3Hz,2H),7.80(d,J＝8.9Hz,2H),4.59–4.43(m,3H),3.39(d,J＝2.3Hz,3H).19F NMR(376MHz,Chloroform-d)δ-75.27(dd,J＝13.2,9.1Hz),-78.51(ddd,J＝19.1,13.1,6.8Hz). 13C NMR(101MHz,Chloroform-d)δ163.28–155.65(m),134.51,132.34,130.69,121.02,120.43(q,J＝319.5Hz),68.52(dd,J＝31.7,17.4Hz),42.14(d,J＝8.1Hz),25.34.MS(EI):m/z 279.0(％)(100),351.0(M +).HRMS:Calculated for C 10H 10F 2SBr:278.9643；Found:278.9649。
实施例20
Figure PCTCN2022115642-appb-000064
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，3.24g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得4.39g粘稠液体，产率91.5％。 1H NMR(400MHz,Chloroform-d)δ7.87(d,J＝8.3Hz,2H),7.80(d,J＝8.9Hz,2H),4.59–4.43(m,3H),3.39(d,J＝2.3Hz,3H).19F NMR(376MHz,Chloroform-d)δ-75.27(dd,J＝13.2,9.1Hz),-78.51(ddd,J＝19.1,13.1,6.8Hz). 13C NMR(101MHz,Chloroform-d)δ163.28–155.65(m),134.51,132.34,130.69,121.02,120.43(q,J＝319.5Hz),68.52(dd,J＝31.7,17.4Hz),42.14(d,J＝8.1Hz),25.34.MS(EI):m/z 279.0(％)(100),351.0(M +).HRMS:Calculated for C 10H 10F 2SBr:278.9643；Found:278.9649。
实施例21
Figure PCTCN2022115642-appb-000065
无水无氧冰水浴下，向的1000mL反应瓶中加入NaH(9.0g,60％,225mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环500mL中，然后在冰水浴下慢慢滴加硫酚(22.4g,180.0mmol)，滴加完毕后室温下搅拌反应60分钟。然后再次冰水浴冷却，慢慢加入溴三氟丙烯(360mmol,63g)，滴加完毕后自然升至25度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物43.1g,分离产率为82％。 1H NMR(400MHz,CDCl 3)δ7.36(d,J＝8.0Hz,2H),7.13(d,J＝8.0Hz,2H),3.72–3.69(m,2H),2.34(s,3H). 19F NMR(376MHz,CDCl 3)δ-81.91(dt,J＝34.9,2.0Hz,1F),-87.65(dt,J＝34.9,2.7Hz,1F). 13C NMR(101MHz,CDCl 3)δ154.1(dd,J＝291.3,287.1Hz),138.3,133.3,129.8,129.5,78.4(dd,J＝37.0,22.1Hz),37.7,21.1.MS(FI):m/z(％)280(100)([M] +).HRMS(FI)m/z:([M] +)Calculated for C 10H 9BrF 2S:277.9571；Found:277.9575.
实施例22
Figure PCTCN2022115642-appb-000066
无水无氧下，向100mL三颈瓶中加入硫醚(16.5mmol，4.6g)，加入超干的DCM(10ml)，然后加入MeOTf(2.5g,15mmol)，室温反应4h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，乙醚重结晶得白色固体5.5g,产率为83％. 1H NMR(400MHz,CDCl 3)δ7.90(d,J＝8.4Hz,2H),7.50(d,J＝8.4Hz,2H),5.16(d,J＝14.4Hz,1H),4.92–4.84(m,1H),3.57(s,3H),2.49(s,3H). 19F NMR(376MHz,CDCl 3)δ-72.74(dd,J＝11.2,4.4Hz,1F),-77.43(d,J＝11.3Hz,1F),-78.49(s,3F). 13C NMR(101MHz,CDCl 3)δ156.3(dd,J＝300.6,292.5Hz),147.2,132.0,131.2,120.5(q,J＝319.8Hz),117.4,68.8(dd,J＝35.7,29.8Hz),49.3,26.3,21.7.MS(ESI):m/z(％)138,153,245,293(100),([M-OTf] +).HRMS(ESI)m/z:([M-OTf] +)Calculated for C 11H 12BrF 2S:292.9806；Found:292.9798.
实施例23
Figure PCTCN2022115642-appb-000067
无水无氧冰水浴下，向的1000mL反应瓶中加入NaH(0.9g,60％,22.5mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干1，4二氧六环500mL中，然后在冰水浴下慢慢滴加硫酚(2.48g,20.0mmol)，滴加完毕后室温下搅拌反应60分钟。然后再次冰水浴冷却，慢慢加入氯三氟丙烯(气体，过量的)，滴加完毕后自然升至25℃搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物2.9克,分离63％。 1H NMR(400MHz,CDCl3) δ7.34(d,J＝7.6Hz,2H),7.11(d,J＝7.6Hz,2H),3.65–3.58(m,2H),2.32(s,3H). 19F NMR(376MHz,CDCl3)δ-87.12(d,J＝38.2Hz,1F),-92.61(d,J＝38.3Hz,1F). 13C NMR(101MHz,CDCl3)δ155.7(dd,J＝289.5Hz,288.3Hz),138.3,133.2,129.8,129.5,90.1(dd,J＝41.1,19.2Hz),36.4(d,J＝2.2Hz),21.1.
实施例24
Figure PCTCN2022115642-appb-000068
无水无氧下，向100mL三颈瓶中加入硫醚(1.18g,5.0mmol)，加入超干的DCM(10ml)，然后加入MeOTf(0.72g,4.3mmol)，室温反应4h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，乙醚重结晶得白色固体1.9g,产率为92％. 1H NMR(400MHz,Chloroform-d) 1H NMR(400MHz,CDCl3)δ7.90(d,J＝7.8Hz,2H),7.49(d,J＝7.8Hz,2H),5.03(d,J＝14.0Hz,1H),4.90–4.78(m,1H),3.56(s,3H),2.49(s,3H). 19F NMR(376MHz,CDCl3)δ-77.60(d,J＝14.2Hz),-78.62(s,3F),-82.73(d,J＝13.5Hz). 13C NMR(101MHz,CDCl3)δ156.7(t,J＝296.7Hz),147.1,132.0,131.1,120.6(q,J＝320.1Hz),117.6,83.0(dd,J＝40.1,26.3Hz),48.1,26.4,21.7.
实施例25
Figure PCTCN2022115642-appb-000069
无水无氧冰水浴下，向的1000mL反应瓶中加入NaH(9.0g,60％,225mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干1，4二氧六环500mL中，然后在冰水浴下慢慢滴加硫醇(24.9g,180.0mmol)，滴加完毕后室温下搅拌反应60分钟。然后再次冰水浴冷却，慢慢加入溴三氟丙烯(360mmol,63g)，滴加完毕后自然升至25度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物43.1g,分离产率为82％。 1H NMR(400MHz,CDCl 3)δ7.32–7.26(m,2H),7.24–7.17(m,3H),3.44(dd,J＝2.8,2.0Hz,2H),2.92–2.85(m,2H),2.78–2.72(m,2H). 19F NMR(376MHz,CDCl 3)δ-81.70(dt,J＝37.6,2.6Hz,1F),-87.64(dt,J＝37.6,2.6Hz,1F). 13C NMR(101MHz,CDCl3)δ153.9(dd,J＝290.3,287.7Hz),140.0,128.5,128.4,126.5,78.9(dd,J＝37.1,21.0Hz),35.8,33.1,32.8.MS(FI):m/z(％)186,294(100)([M] +).HRMS(FI)m/z:([M] +)Calculated for C 11H 11F 2SBr:291.9727；Found:291.9721.
实施例26
Figure PCTCN2022115642-appb-000070
无水无氧下，向100mL圆底瓶中加入硫醚(50.4mmol，14.77g)，加入超干的乙醚(30ml)，然后加入MeOTf(8.6ml,75.6mmol)，室温反应12h。过滤，得白色固体21.52g,产率为93.4％.1H NMR(400MHz,Chloroform-d)δ7.33(dt,J＝24.0,7.3Hz,5H),4.64(d,J＝14.4Hz,1H),4.29(d,J＝ 12.5Hz,1H),3.89(t,J＝7.3Hz,2H),3.19(t,J＝7.2Hz,2H),2.90(s,3H).19F NMR(376MHz,Chloroform-d)δ-71.62(d,J＝12.3Hz),-76.39(d,J＝12.5Hz),-78.54.13C NMR(101MHz,Chloroform-d)δ156.14(dd,J＝299.8,293.0Hz),135.72,129.40,128.74,128.04,120.52(q,J＝319.7Hz),68.50(dd,J＝35.9,29.1Hz),44.23(d,J＝2.1Hz),43.58,30.83,22.54.MS(EI):m/z(％)153.1(100),215.1(M+).HRMS:Calculated for C10H13F2S:306.9962；Found:306.9964。
实施例27
Figure PCTCN2022115642-appb-000071
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入2-甲基-溴二氟丙烯(25mmol,4.28g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物3.77g,分离产率为88％。
实施例28
Figure PCTCN2022115642-appb-000072
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，2.62g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得3.90g粘稠液体，产率92％。
实施例29
Figure PCTCN2022115642-appb-000073
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入2-苯基-溴二氟丙烯(25mmol,5.83g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物4.97g,分离产率为90％。
实施例30
Figure PCTCN2022115642-appb-000074
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，3.37g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得4.44g粘稠液体，产率90％。
实施例31
Figure PCTCN2022115642-appb-000075
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入2-苯乙基-溴二氟丙烯(25mmol,6.53g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物5.60g,分离产率为92％。
实施例32
Figure PCTCN2022115642-appb-000076
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，3.72g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得4.62g粘稠液体，产率88％。
实施例33
Figure PCTCN2022115642-appb-000077
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入2-对甲酸甲酯苯基-溴二氟丙烯(25mmol,7.28g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物6.29g,分离产率为94％。
实施例34
Figure PCTCN2022115642-appb-000078
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，4.08g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得4.86g粘稠液体，产率87％。
实施例35
Figure PCTCN2022115642-appb-000079
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入2-对乙炔基苯基-溴二氟丙烯(25mmol,6.43g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物4.21g,分离产率为70％。
实施例36
Figure PCTCN2022115642-appb-000080
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，3.67g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得4.37g粘稠液体，产率84％。
实施例37
Figure PCTCN2022115642-appb-000081
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入2-对叠氮苄基-溴二氟丙烯(25mmol,7.20g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物5.17g,分离产率为78％。
实施例38
Figure PCTCN2022115642-appb-000082
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，4.04g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得4.72g粘稠液体，产率85％。
实施例39
Figure PCTCN2022115642-appb-000083
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入2-丁炔基-溴二氟丙烯(25mmol,5.23g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物4.44g,分离产率为88％。
实施例40
Figure PCTCN2022115642-appb-000084
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，3.08g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得3.69g粘稠液体，产率79％。
实施例41
Figure PCTCN2022115642-appb-000085
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入溴二氟丁烯(25mmol,4.28g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物3.40g,分离产率为80％。
实施例42
Figure PCTCN2022115642-appb-000086
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，2.62g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得3.74g粘稠液体，产率88％。 1H NMR(400MHz,CDCl 3)δ7.83(d,J＝8.0Hz,2H),7.46(d,J＝8.0Hz,2H),4.56(d,J＝12.8Hz,1H),4.52–4.44(m,1H),3.44(s,3H),2.47(s,3H),1.69(t,J＝3.2Hz,3H). 19F NMR(376MHz,CDCl 3)δ-78.52(s,3F),-84.44–-84.71(m,1F),-85.24–-85.44(m,1F).
实施例43
Figure PCTCN2022115642-appb-000087
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入溴二氟丙烯(25mmol,5.23g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物3.89g,分离产率为77％。
实施例44
Figure PCTCN2022115642-appb-000088
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，3.09g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得4.10g粘稠液体，产率88％。
实施例45
Figure PCTCN2022115642-appb-000089
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入溴二氟丙烯酸甲酯(25mmol,5.38g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物4.49g,分离产率为87％。
实施例46
Figure PCTCN2022115642-appb-000090
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，3.15g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得3.74g粘稠液体，产率79％。
实施例47
Figure PCTCN2022115642-appb-000091
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水 浴冷却，慢慢加入溴二氟丁烯醇苄醚(25mmol,6.93g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物5.64g,分离产率为88％。
实施例48
Figure PCTCN2022115642-appb-000092
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，3.91g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得4.29g粘稠液体，产率79％。
实施例49
Figure PCTCN2022115642-appb-000093
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g，60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g，20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入溴二氟丙烯(25mmol,7.20g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物5.64g,分离产率为85％。
实施例50
Figure PCTCN2022115642-appb-000094
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，4.05g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得4.22g粘稠液体，产率76％。
实施例51
Figure PCTCN2022115642-appb-000095
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤 三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入溴二氟丙烯(25mmol,4.88g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物4.24g,分离产率为89％。
实施例52
Figure PCTCN2022115642-appb-000096
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，2.91g)，加入超干的DCM(10ml)，然后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得3.52g粘稠液体，产率78％。
实施例53
Figure PCTCN2022115642-appb-000097
向反应容器中称取Pd(PPh 3) 2Cl 2(0.05equiv)和t-BuDavePhos(0.1equiv)，氩气保护条件下加入制备好的锌试剂(1.5equiv，四氢呋喃溶液)和硫醚(1.0equiv)原料，最后加入MeCN(MeCN：THF＝1：1，MeCN与锌试剂摩尔体积比为0.5mol/L)，室温条件下反应12小时。其中，锌试剂的制备可采用本领域常规制备方法，也可采用本发明提供的方法，如无特殊说明，参照本制备方案制备下列的化合物。
产物：
Figure PCTCN2022115642-appb-000098
104m g，无色液体，产率36％，PE柱层析。 1H NMR(400MHz,CDCl 3)δ7.43–7.34(m,4H),7.32–7.24(m,3H),7.24–7.18(m,1H),7.18–7.12(m,2H),3.56–3.51(m,2H),2.94–2.83(m,2H),2.81–2.66(m,2H). 19F NMR(376MHz,CDCl 3)δ-88.76(d,J＝37.1Hz,1F),-88.96(d,J＝37.0Hz,1F). 13C NMR(101MHz,CDCl 3)δ154.4(dd,J＝293.3,289.7Hz),140.3,132.4(t,J＝3.1Hz),128.5,128.4,128.3(t,J＝3.2Hz),127.8,126.4,90.5(dd,J＝19.4,14.8Hz),36.0,33.0,29.9(d,J＝2.8Hz).
产物：
Figure PCTCN2022115642-appb-000099
0.9g，黄色液体，产率28％。 1H NMR(400MHz,CDCl 3)δ7.33–7.25(m,4H),7.24–7.19(m,1H),7.18–7.14(m,2H),6.93–6.87(m,2H),3.80(s,3H),3.51(t,J＝2.2Hz,2H),2.91–2.82(m,2H),2.76–2.68(m,2H). 19F NMR(376MHz,CDCl 3)δ-89.66(d,J＝39.7Hz,1F),-89.97(d,J＝39.6Hz,1F). 13C NMR(101MHz,CDCl 3)δ159.0,155.7(dd,J＝292.3Hz,J＝292.5Hz),140.3,133.1,129.5(t,J＝3.2Hz),128.5,126.3,124.5(t,J＝3.4Hz),113.9,89.9(dd,J＝19.8,15.0Hz),55.2,36.0,33.0,30.0(d,J＝2.7Hz).
产物：
Figure PCTCN2022115642-appb-000100
78mg，无色液体，产率28％，硅胶柱色谱分离(石油醚/乙酸乙酯＝100：1)。 1H NMR(400MHz,CDCl 3)δ 1H NMR(400MHz,CDCl 3)δ7.39(d,J＝8.0Hz,2H),7.35–7.24(m,4H),7.21(dd,J＝8.6,6.8Hz,1H),7.17–7.10(m,2H),3.55(s,2H),2.86(dd,J＝9.7,6.2Hz,2H),2.73(dd,J＝9.7,6.1Hz,2H),1.32(s,9H). 19F NMR(376MHz,CDCl 3)δ-88.68(d,J＝37.9Hz),-88.81(d,J＝37.8Hz). 19F NMR(376MHz,CDCl 3)δ-88.89(d,J＝37.5Hz,1F),-89.02(d,J＝37.9Hz,1F). 13C NMR(101MHz,CDCl 3)δ154.4(dd,J＝292.7,290.2Hz),150.6,140.3,129.3,128.4,127.9(t,J＝3.1Hz),126.3,125.4,90.3(dd,J＝18.7,15.3Hz),36.1,34.5,33.0,31.2,29.7.
产物：
Figure PCTCN2022115642-appb-000101
79mg，无色油状液体，产率22％，硅胶柱色谱分离(石油醚/乙酸乙酯＝80：1)。 1H NMR(400MHz,CDCl 3)δ8.04(d,J＝8.0Hz,2H),7.46(d,J＝8.0Hz,2H),7.35–7.18(m,3H),7.16(d,J＝7.2Hz,2H),4.38(q,J＝7.2Hz,2H),3.5(s,2H),2.97–2.83(m,2H),2.79–2.64(m,2H),1.39(t,J＝7.2Hz,3H). 19F NMR(376MHz,CDCl 3)δ-86.48(d,J＝32.6Hz,1F),-86.61(d,J＝32.6Hz,1F). 13C NMR(101MHz,CDCl 3)δ166.1,154.6(dd,J＝295.0,291.3Hz),140.1,137.0(d,J＝2.7Hz),129.7,129.6,128.5,128.4,128.2(t,J＝3.1Hz),126.4,90.3(dd,J＝19.8,14.4Hz),61.0,35.9,33.1,29.5,14.3.MS(FI):m/z(％)362(100).([M] +)；HRMS(FI)m/z:([M] +)Calculated for C 20H 20F 2O 2S:362.1147；Found:362.1151.
Figure PCTCN2022115642-appb-000102
无水无氧条件下(Ar)，将原料A在LiAlH 4作还原酯基后淬灭，然后常规有机溶剂萃取后处理后加入1.2倍当量的DPPA与1.2倍当量的DBU，得到产物656mg，无色油状液体，产率38％，硅胶柱色谱分离(石油醚/乙酸乙酯＝80：1)。 19F NMR(376MHz,CDCl 3)δ-88.1(d,J＝35.7Hz,1F),-88.2(d,J＝43.6Hz,1F). 1H NMR(400MHz,CDCl 3)δ7.40(d,J＝8.4Hz,2H),7.32-7.28(m,4H),7.24-7.21(m,1H),7.20-7.15(m,2H),4.35(s,2H),3.54(t,J＝2.0Hz,2H),2.89–2.85(m,2H),2.76–2.72(m,2H).
产物：
Figure PCTCN2022115642-appb-000103
1.1g，黄色液体，产率34％。 1H NMR(400MHz,Chloroform-d)δ7.42–7.10(m,6H),6.96(d,J＝9.5Hz,2H),6.85(d,J＝8.5Hz,1H),3.80(s,3H),3.53(s,2H),2.87(t,J＝7.8Hz,2H),2.74(dd,J＝9.3,6.4Hz,2H). 19F NMR(376MHz,Acetonitrile-d3)δ-93.35(d,J＝36.5Hz,1F),-93.91(d,J＝36.5Hz,1F). 13C NMR(101MHz,Chloroform-d)δ159.55,158.05–150.55(m),140.32,133.78(t,J＝4.0Hz),129.46,128.47,128.44,126.36,120.71(t,J＝3.2Hz),114.35(t,J＝3.6Hz),113.08,90.50(dd,J＝20.0,13.7Hz),55.21,36.03,33.09,29.92,29.89。
产物：
Figure PCTCN2022115642-appb-000104
0.88g，淡黄色液体，产率46％。 1H NMR(400MHz,Chloroform-d)δ7.48(d,J＝7.7Hz,2H),7.32(dd,J＝12.0,7.5Hz,4H),7.24(d,J＝14.6Hz,1H),7.24(s,1H),7.18(d,J＝7.1Hz,2H),3.53(s,2H),2.96–2.80(m,2H),2.80–2.59(m,2H),0.27(s,9H). 19F NMR(376MHz,Chloroform-d)δ-87.39(d,J＝34.3Hz),-87.60(d,J＝34.4Hz). 13C NMR(126MHz,Chloroform-d)δ158.18–150.25(m),140.21,132.54,132.01,131.80,131.48,128.49,128.46,128.06(t,J＝3.4Hz),126.41,122.52,104.61,95.01,92.11–88.53(m),35.97,33.10,29.54,-0.08。
实施例54 3，3-二氟烯丙基鎓盐制备例
Figure PCTCN2022115642-appb-000105
无水无氧条件下，0℃条件下，向实施例53得到硫醚的二氯甲烷溶液(1.05equiv,0.5M的CH 2Cl 2溶液)中缓慢滴加三氟甲磺酸甲酯(1.0equiv)，室温搅拌过夜。反应结束后向体系中滴加乙醚，产物即可析出。以此方法制备下述硫盐。
产物：
Figure PCTCN2022115642-appb-000106
1.8g，白色固体，产率79％。m.p.48.7-51.5℃. 1H NMR(400MHz,CDCl 3)δ7.47–7.33(m,3H),7.35–7.23(m,5H),7.17(d,J＝6.8Hz,2H),4.61(d,J＝14.0Hz,1H),4.40(d,J＝14.0Hz,1H),3.74(t,J＝7.2Hz,2H),3.49(s,3H),3.16–3.00(m,2H),2.73(s,3H). 19F NMR(376MHz,CDCl 3)δ-78.39(s,3F),-79.54(d,J＝15.2Hz,1F),-79.77(d,J＝15.2Hz,1F). 13C NMR(126MHz,CDCl 3)δ156.0(t,J＝299.2Hz),135.7,129.4,129.2,129.1,128.8(t,J＝2.6Hz),128.6,128.2(t,J＝2.5Hz),127.9,120.4(q,J＝319.6Hz),84.4(dd,J＝21.3,18.4Hz),43.4,41.1(d,J＝4.3Hz),30.7,22.5.MS(ESI):m/z(％)105,305(100).([M-OTf] +)；HRMS(ESI)m/z:([M-OTf] +)Calculated for C 18H 19F 2S:305.1170；Found:305.1162.
产物：
Figure PCTCN2022115642-appb-000107
730mg，粘稠液体，产率73％。 1H NMR(400MHz,CDCl 3)δ7.37–7.21(m,5H),7.18(d,J＝7.3Hz,2H),6.92(d,J＝8.3Hz,2H),4.56(d,J＝13.9Hz,1H),4.38(d,J＝13.8Hz,1H),3.80(s,3H),3.71(t,J＝7.4Hz,2H),3.16–2.95(m,2H),2.73(s,3H). 19F NMR(400MHz,CDCl 3)δ-78.41(s,3F),-81.16(d,J＝19.0Hz,1F),-81.30(d,J＝19.0Hz,1F). 13C NMR(101MHz,CDCl 3)δ159.9,155.6(t,J＝297.1Hz),135.7,129.4,129.0,128.5,127.6,120.53(q,J＝320.5Hz),120.49,114.6,83.8(t,J＝19.8Hz),55.1,43.0,41.1,30.3,22.2.MS(ESI):m/z(％)145.1,335.1(100),([M-OTf] +).HRMS(ESI)m/z:([M-OTf] +)Calculated for C 19H 21OF 2S:335.1276；Found:335.1276.
产物：
Figure PCTCN2022115642-appb-000108
370mg，白色固体，产率43％。m.p.86.3-87.4℃；1H NMR(400MHz,CDCl3)δ7.43(d,J＝7.6Hz,2H),7.34–7.22(m,5H),7.16(d,J＝6.8Hz,2H),4.61(d,J＝13.8Hz,1H),4.42(d,J＝13.8Hz,1H),3.73(t,J＝7.2Hz,2H),3.20–2.95(m,2H),2.76(s,3H),1.31(s,9H).19F NMR(400MHz,CDCl3)δ-83.65(s,3F),-85.20(d,J＝16.4Hz,1F),-85.49(d,J＝16.4Hz,1F).13C NMR(126MHz,CDCl3)δ156.0(dd,J＝299.1,297.7Hz),152.6,135.7,129.2,128.6,127.84,127.77(t,J＝2.5Hz),126.4,120.5(q,J＝319.7Hz),84.2(dd,J＝21.3,18.2Hz),43.3,41.0(d,J＝3.8Hz),34.7,31.1,30.7,22.5.MS(ESI):m/z(％)215.1,361.2(100),([M-OTf]+).HRMS(ESI)m/z:([M-OTf]+)Calculated for C22H27F2S:361.1796；Found:361.1799.
产物：
Figure PCTCN2022115642-appb-000109
840mg，白色固体，产率84％。m.p.104.8-105.6℃； 1H NMR(400MHz,CDCl 3)δ8.08(d,J＝7.6Hz,2H),7.44(d,J＝7.6Hz,2H),7.36–7.23(m,3H),7.19(d,J＝6.4Hz,2H),4.72(d,J＝14.0Hz,1H),4.48(d,J＝14.0Hz,1H),4.39(q,J＝6.8Hz,2H),3.81(t,J＝6.8Hz,2H),3.15–3.00(m,2H),2.74(s,3H),1.40(t,J＝7.0Hz,3H). 19F NMR(376MHz,CDCl 3)δ-77.38(d,J＝10.8Hz,1F),-77.70(d,J＝10.8Hz,1F),-78.48(s,3F). 13C NMR(126MHz,CDCl 3)δ165.7,156.3(dd,J＝300.5,299.6Hz),135.7,133.3(t,J＝3.2Hz),131.1,130.4,129.3,128.6,128.3(t,J＝3.2Hz),128.0,84.3(t,J＝19.7Hz),61.4,43.6,40.8,30.8,22.6,14.3.MS(ESI):m/z(％)356,377(100)([M-OTf] +).HRMS(ESI)m/z:([M-OTf] +)Calculated for C 21H 23F 2O 2S:377.1381；Found:377.1380.
产物：
Figure PCTCN2022115642-appb-000110
880mg，白色固体，产率91％。 19F NMR(376MHz,CDCl 3)δ-78.5(s,3F),-78.9(d,J＝16.1Hz,1F),-79.2(d,J＝15.0Hz,1F). 1H NMR(400MHz,CDCl 3)δ7.37(s,3H),7.34-7.25(m,4H),7.19-7.16(m,2H),4.65(d,J＝13.2Hz,1H),4.44(d,J＝14.4Hz,1H),4.36(s,2H),3.76(t,J＝7.6Hz,2H),3.15–3.05(m,2H),2.74(s,3H).
产物：
Figure PCTCN2022115642-appb-000111
660mg，粘稠液体，68％。 1H NMR(400MHz,Chloroform-d)δ7.38–7.13(m,6H),6.98–6.85(m,3H),4.61(d,J＝14.0Hz,1H),4.40(d,J＝14.1Hz,1H),3.83(s,3H),3.74(t,J＝7.3Hz,2H),3.09(q,J＝6.8Hz,2H),2.74(s,3H). 19F NMR(376MHz,Chloroform-d)δ-78.38(s,3F),-79.22(d,J＝14.7Hz,1F),-79.42(d,J＝14.6Hz,1F). 13C NMR(126MHz,Chloroform-d)δ160.26,158.87–153.36(m),135.73,130.57,130.19(t,J＝2.6Hz),129.34,128.66,127.94,120.43,115.25,113.65(t,J＝2.9Hz),84.49(dd,J＝21.5,18.2Hz),55.50,43.48,41.16(d,J＝4.4Hz),30.79,22.56.
产物：
Figure PCTCN2022115642-appb-000112
773mg，白色固体，产率61％。 1H NMR(400MHz,Chloroform-d)δ7.51(d,J＝7.2Hz,2H),7.40–7.24(m,5H),7.19(d,J＝7.0Hz,2H),4.66(s,1H),4.44(s,1H),3.80(s,2H),3.11(s,2H),2.71(s,3H),0.26(s,9H). 19F NMR(376MHz,Chloroform-d)δ-78.21(d,J＝12.6Hz),-78.49.
实施例55
Figure PCTCN2022115642-appb-000113
无水无氧冰水浴下，向的100mL反应瓶中加入NaH(1.20g,60％,30mmol)，然后用正戊烷洗涤三次(每次60mL)除去钠氢中的煤油，然后将所得的活性钠氢悬浮于超干二氧六环80mL中，然后在冰水浴下慢慢滴加硫酚(3.79g,20.0mmol)，滴加完毕后室温下搅拌反应30分钟。然后再次冰水浴冷却，慢慢加入2-丁烯基二氟丙烯(25mmol,5.24g)，滴加完毕后自然升至室温度搅拌24h。饱和氯化铵淬灭后EA萃取，干燥后浓缩。PE柱层析，得产物4.0g,分离产率为79％。
实施例56
Figure PCTCN2022115642-appb-000114
无水无氧下，向50mL圆底瓶中加入硫醚(12.2mmol，3.10g)，加入超干的DCM(10ml)，然 后加入MeOTf(1.2ml,11.2mmol)，室温反应12h。旋干，再加入甲醇溶解，用正己烷洗(分层)，洗至正己烷层荧光极弱，然后将甲醇旋干，抽干，得2.80g粘稠液体，产率60％。 1H NMR(400MHz,CDCl 3)δ7.83(d,J＝7.8Hz,2H),7.45(d,J＝7.8Hz,2H),5.76–5.59(m,1H),5.02(d,J＝17.2Hz,1H),4.98(d,J＝10.0Hz,1H),4.53(d,J＝13.2Hz,1H),4.48–4.39(m,1H),3.43(s,3H),2.45(s,3H),2.31–2.00(m,4H). 19F NMR(376MHz,CDCl 3)δ-78.30(s,3F),-82.92(d,J＝25.1Hz,1F),-83.73(d,J＝25.1Hz,1F).
实施例57
Figure PCTCN2022115642-appb-000115
氩气保护条件下，向碳酸钾(2.0equiv.)的甲醇溶液中，加入上一步的产物和苯乙硫醇(1.0equiv.)，室温搅拌过夜。过滤反应体系，旋干，柱层析，得到目标化合物，以此方法制备下述化合物。
产物：
Figure PCTCN2022115642-appb-000116
4.6g，黄色液体，52％。 19F NMR(376MHz,CDCl 3)δ-87.53(d,J＝44.3Hz),-89.74(dd,J＝44.1,24.3Hz). 1H NMR(400MHz,CDCl 3)δ7.38–7.26(m,4H),7.25–7.14(m,5H),4.15(ddd,J＝24.3,10.8,1.8Hz,1H),2.96–2.81(m,4H),2.81–2.65(m,4H),2.52(t,J＝7.2Hz,2H),1.71–1.42(m,7H).
产物：
Figure PCTCN2022115642-appb-000117
466mg,黄色液体，13％。 19F NMR(376MHz,CDCl 3)δ-87.32(d,J＝43.8Hz),-89.60(dd,J＝43.8,24.2Hz). 1H NMR(400MHz,CDCl 3)δ7.31(t,J＝7.1Hz,2H),7.26–7.10(m,3H),4.16(dd,J＝24.7,11.4Hz,1H),3.68–3.42(m,1H),3.27(t,J＝6.6Hz,2H),2.94–2.80(m,2H),2.79–2.62(m,2H),1.75–1.37(m,6H).
产物：
Figure PCTCN2022115642-appb-000118
4.5g，黄色液体，58％。 19F NMR(376MHz,CDCl 3)δ-87.84(d,J＝44.8Hz),-90.08(dd,J＝44.7,24.4Hz). 1H NMR(400MHz,CDCl 3)δ7.30(t,J＝7.5Hz,2H),7.21(dd,J＝14.6,7.2Hz,3H),4.23–4.05(m,1H),3.67(s,3H),3.55–3.41(m,1H),2.98–2.80(m,2H),2.79–2.63(m,2H),2.30(t,J＝7.5Hz,2H), 1.70–1.19(m,14H).
实施例58
Figure PCTCN2022115642-appb-000119
250mL的三口烧瓶中加入(5.53g,40mmol,2.0equiv)，加入二氟烯丙基化合物(20mmol,1.0equiv)和甲醇(MeOH，60mL)，滴入硫醇(20mmol,1.0equiv)室温搅拌过夜，过滤，乙酸乙酯洗涤三次，盐水洗涤，无水硫酸钠干燥，干燥后浓缩，石油醚柱层析纯化，得无色油状产物(3.46g,72％yield). 1H NMR(400MHz,CDCl 3)δ7.31(t,J＝7.2Hz,2H),7.25–7.17(m,3H),4.15(ddd,J＝24.4,10.9,2.0Hz,1H),3.54–3.42(m,1H),3.01–2.59(m,4H),1.77–1.58(m,1H),1.55–1.43(m,1H),1.41–1.33(m,2H),1.32–1.24(m,6H),0.89(t,J＝6.8Hz,3H). 19F NMR(376MHz,CDCl 3)δ-87.90(dd,J＝45.0,2.0Hz),-90.12(dd,J＝45.0,24.5Hz). 13C NMR(101MHz,CDCl 3)δ157.3(t,J＝288.9Hz),140.4,128.4,126.3,82.0(t,J＝19.6Hz),38.8,38.7,36.2,35.1,32.3,31.6,28.8,27.1,22.5,14.0.MS(FI):m/z(％)298(100)([M] +).HRMS(FI)m/z:([M] +)Calculated for C 17H 24F 2S:298.1561；Found:298.1567.
Figure PCTCN2022115642-appb-000120
无水无氧下，向100mL史莱克管中加入硫醚(1.4g,4.7mmol,1.05equiv)，加入超干的DCM(10ml)，冰水浴中加入MeOTf((4.5mmol,1.0equiv)，室温搅拌反应过夜。加入乙酸乙酯，有粘稠油状液体产生，乙酸乙酯洗涤三次并真空干燥，得目标产物(1.25g,76yield,纯度90％(w/w)). 1H NMR(400MHz,CD 2Cl 2)非对映异构体混合物:δ7.35–7.19(m,5H),4.51–4.35(m,1H),4.34–4.23(m,0.45H),4.18–4.07(m,0.55H),3.49–3.37(m,2H),3.18–3.02(m,2H),2.77(s,1.7H)(2.74(s,1.3H)),1.85–1.61(m,2H),1.32–1.15(m,8H),0.81(t,J＝6.6Hz,3H). 19F NMR(376MHz,CD 2Cl 2)非对映异构体混合物:δ-75.34(d,J＝16.6Hz,0.56F),-75.52(d,J＝15.8Hz,0.44F),-77.14–-77.34(m,1F),-78.96(s,3F).MS(ESI):m/z(％)153,167,181,313(100),([M-OTf] +).HRMS(ESI)m/z:([M-OTf] +)Calculated for C 18H 27F 2S:313.1796；Found:313.1794.
以下实施例为3，3-二氟烯丙基硫鎓盐、硒鎓盐、碲鎓盐和其衍生物在合成化学中的应用。
应用实施例预实验：
反应溶剂的优化
Figure PCTCN2022115642-appb-000121
无水无氧下，向反应管中加入磁子，硫盐(72.9mg,0.2mmol)和CuBr(2.8mg,0.02mmol)，抽换气三次，Ar下加入2mL的超干无水的下表所述溶剂，然后搅拌均匀，室温下慢慢滴加锌试剂SM2(0.464M)，滴加完毕后室温搅拌反应3h。反应结果见下表：
Figure PCTCN2022115642-appb-000122
注：催化剂空气下称取；目标化合物表示目标化合物；SM1表示原料, 19F％指以氟苯为内标物 19F NMR测定收率；ND表示未检出。
本步骤的偶联反应的温度可不做特别限定，在-78至35℃范围内均可进行。
锌试剂[C]-[Zn]用量的优化：
Figure PCTCN2022115642-appb-000123
实验操作参见反应溶剂的优化实验，锌试剂的条件如下表所述：
Figure PCTCN2022115642-appb-000124
注：ND表示未检出。
催化剂类型优化:
Figure PCTCN2022115642-appb-000125
实验操作：1a(0.2mmol,1.0equiv),4a(1.2equiv),THF(2mL)，操作步骤参见反应溶剂的优化实验，催化剂种类如下表所示：
Figure PCTCN2022115642-appb-000126
注： 19F％指以氟苯为内标物 19F NMR测定收率；ND表示未检出。 cCuCl(99.999％)使用。
考虑到CuBr成本低，易操作，下述实验以CuBr为催化剂进行优化。
催化剂用量优化:
Figure PCTCN2022115642-appb-000127
催化剂用量见下表：
Figure PCTCN2022115642-appb-000128
注：trace表示痕量。
对比例1～6:
如无特殊说明，操作条件参见上述优化实验实施例，对比条件见下表：
Figure PCTCN2022115642-appb-000129
锌试剂的制备例：
芳基锌试剂的通用方法：
1)格氏试剂转化法：
Figure PCTCN2022115642-appb-000130
50ml史莱克瓶，称取镁屑，手套箱称取氯化锂，抽泣状态下，烤枪烤至氯化锂不挂壁，自然恢复室温，加入THF，置于冰水浴中，加入DIBAL-H，搅拌至反应无气泡生成，然后快速加入芳基溴原料，冰浴下搅拌10min，恢复室温，搅拌反应4h，滴定浓度。滤头过滤，定量加入氯化锌溶液搅拌反应1h，滴定浓度。
制备例1～3
Figure PCTCN2022115642-appb-000131
2)碘镁交换法：(含官能团的锌试剂)
Figure PCTCN2022115642-appb-000132
50毫升史莱克瓶，加磁子，抽换气三次，Ar下加入i-Pr-MgCl-LiCl的THF溶液，置于相应冷浴温度下，保温搅拌5min，然后加入相应的芳基碘试剂(固体分批加，液体滴加)，GC监测原料是否转化完全。待完全转化后，滴定格氏试剂浓度，根据格氏试剂的浓度与体积，加入氯化锌溶液，室温 搅拌20min。再次滴定浓度。
制备例4～8：
Figure PCTCN2022115642-appb-000133
烷基锌试剂制备：
锌粉插入法：
Figure PCTCN2022115642-appb-000134
制备例9～16：
Figure PCTCN2022115642-appb-000135
将锌粉，氯化锂称入封管中，抽换气三次后，抽气状态下，烤枪烤5-10min，恢复室温，加入THF搅拌，然后计入1，2-二溴乙烷，60℃油浴加热至冒泡，冷至室温，然后加入一粒碘和TMSCl，60℃油浴加热搅拌反应20min，之后再冷至室温，加入原料，50～80℃油浴搅拌反应18h。(上述的C表示锌试剂产物的浓度)
应用实施例1
其中以
Figure PCTCN2022115642-appb-000136
和锌试剂的反应为例，
如无特殊说明，反应操作及条件参考上述实施例(应用实施例预实验)，以下表所示的锌试剂进行反应，反应结果如下表所示。
Figure PCTCN2022115642-appb-000137
Figure PCTCN2022115642-appb-000138
Figure PCTCN2022115642-appb-000139
Figure PCTCN2022115642-appb-000140
Figure PCTCN2022115642-appb-000141
注：以 19F NMR测定收率。
应用实施例
参见应用实施例部分，以下表所示的锌试剂进行反应，反应结果如下表所示：
Figure PCTCN2022115642-appb-000142
Figure PCTCN2022115642-appb-000143
Figure PCTCN2022115642-appb-000144
注：以 19F NMR测定收率。
应用实施例2
Figure PCTCN2022115642-appb-000145
将2.5mol％的CuBr加入25mL的史莱克瓶中，加入式C所示的二氟烯丙基鎓盐(0.5mmol,1.0equiv)，抽真空充Ar三次。加入2.0mL的THF，滴加式[C]-[Zn]所示锌试剂(1.2equiv)室温下搅拌3小时进行反应。以氟苯为内标试剂采用 19F NMR测定产物收率，NH 4Cl淬灭反应并采用EtOAc稀释干燥，水相采用乙酸乙酯洗涤(3×10mL),有机相采用Na 2SO 4干燥，过滤，收集。滤液采用柱层析或制备型反相HPLC纯化得到目标化合物。
反应结果如下所示：
产物：
Figure PCTCN2022115642-appb-000146
黄色油状液体，114mg，>99％yield，α/γ>99:1  19F NMR测定，采用FP ECOFLEX C18纯化(流动相：MeCN:H 2O＝7:3) 1H NMR(400MHz,CDCl 3)δ7.66(d,J＝8.4Hz,2H),7.63–7.57(m,4H),7.47(t,J＝7.6Hz,2H),7.39(t,J＝7.6Hz,1H),6.30–6.10(m,1H),5.63(dt,J＝17.4,2.8Hz,1H),5.52(d,J＝10.8Hz,1H). 19F NMR(376MHz,CDCl 3)δ-93.37(d,J＝9.5Hz,2F). 13C NMR(101MHz,CDCl 3)δ142.9,140.2,135.1(t,J＝27.7Hz),133.7(t,J＝30.1Hz),128.9,127.8,127.21,127.15,126.0(t,J＝5.6Hz),119.8(t,J＝9.1Hz),119.3(t,J＝238.3Hz).MS(EI):m/z(％)152,203,230([M] +).HRMS(EI)m/z:([M] +)Calculated for C 15H 12F 2:230.0906；Found:230.0902.
产物：
Figure PCTCN2022115642-appb-000147
无色油状液体，120.4mg，91％yield，α/γ>99:1  19F NMR测定. 1H NMR(400MHz,CDCl 3)δ7.69-7.68(m,2H),7.64–7.61(m,4H),7.50-7.46(m,2H),7.42-7.39(m,1H),6.30–6.10(m,1H),5.90-5.89(m,1H),5.71-5.70(m,1H). 19F NMR(376MHz,CDCl 3)δ-95.52(s,2F). 13C NMR(101MHz,CDCl 3)δ143.5,140.02,136.2(t,J＝34.3Hz),132.9(t,J＝27.2Hz),128.9,127.9,127.22,127.16,126.4(t,J＝5.7Hz),117.54(t,J＝5.3Hz),117.46(t,J＝244.2Hz).
产物：
Figure PCTCN2022115642-appb-000148
无色油状物，76mg,83％yield，硅胶色谱纯化分离(DCM:PE＝5:95) 1H NMR(400MHz,CDCl 3)δ7.34(t,J＝7.8Hz,1H),7.09(d,J＝7.8Hz,1H),7.04(s,1H),6.97(d,J＝8.0Hz,1H),6.22-6.04(m,1H),5.66–5.54(m,1H),5.48(d,J＝10.8Hz,1H),3.83(s,3H). 19F NMR(376MHz,CDCl 3)δ-93.64(d,J＝10.0Hz，2F). 13C NMR(101MHz,CDCl 3)δ159.6,137.7(t,J＝27.5Hz),133.7(t,J＝30.0Hz),129.6,119.8(t,J＝9.1Hz),119.1(t,J＝238.7Hz),117.8(t,J＝5.7Hz),115.6(t,J＝1.5Hz),111.0(t,J＝5.9Hz),55.3.MS(FI):m/z(％)91,138,184(100)([M] +).HRMS(FI)m/z:([M] +)Calculated for C 10H 10F 2O:184.0694；Found:184.0692.
产物：
Figure PCTCN2022115642-appb-000149
无色油状物，69mg,65％yield,α/γ>99:1  19F NMR测定，硅胶色谱纯化分离，低沸点， 1H NMR(400MHz,CDCl 3)δ7.44(s,4H),6.38–5.96(m,1H),5.60(dt,J＝17.2,2.8Hz,1H),5.47(d,J＝10.8Hz,1H),1.34(s,9H). 19F NMR(376MHz,CDCl3)δ-93.12(dd,J＝9.6,2.7Hz,2F). 13C NMR(126MHz,CDCl3)δ159.6,137.7(t,J＝27.5Hz),133.7(t,J＝30.0Hz),129.6,119.8(t,J＝9.1Hz),119.1(t,J＝238.7Hz),117.8(t,J＝5.7Hz),115.6(t,J＝1.5Hz),111.0(t,J＝5.9Hz),55.3.
产物：
Figure PCTCN2022115642-appb-000150
微黄色油状物，107mg,95％yield，α/γ>99:1 19F NMR测定，硅胶色谱纯化(石油醚/乙酸乙酯＝100：1)，FP ECOFLEX C18(20g)纯化分离(MeCN:H 2O＝7:3)， 1H NMR(400MHz,CDCl 3)δ8.10(d,J＝8.8Hz,2H),7.57(d,J＝8.8Hz,2H),6.15(ddt,J＝17.2,10.8,9.6Hz,1H),5.57(dt,J＝17.2,2.8Hz,1H),5.51(d,J＝10.8,1H),4.40(q,J＝7.2Hz,2H),1.41(t,J＝7.2Hz,3H). 19F NMR(376MHz,CDCl 3)δ-94.43(dd,J＝9.5,2.8Hz,2F). 13C NMR(126MHz,CDCl 3)δ165.8,140.4(t,J＝27.7Hz),133.3(t,J＝29.7Hz),131.9,129.6,125.5(t,J＝5.7Hz),120.3(t,J＝9.2Hz),118.9(t,J＝239.0Hz),61.2,14.2.MS(EI):m/z(％)133,153,181(100),198,226([M] +).HRMS(EI)m/z:([M] +)Calculated for C 12H 12O 2F 2:226.0800；Found:226.0804.
产物：
Figure PCTCN2022115642-appb-000151
黄色油状物，(93.0mg,62％yield)硅胶色谱纯化分离(石油醚)， 1H NMR(400MHz,CDCl 3)δ7.57–7.53(m,2H),7.44–7.41(m,1H),7.42–7.32(m,1H),6.20–6.04(m,1H),5.60(d,J＝17.6,2.8Hz,1H),5.55(d,J＝11.0Hz,1H). 19F NMR(376MHz,CDCl 3)δ-72.81(s,3F),-93.87(dd,J＝9.8,2.9Hz,2F). 13C NMR(126MHz,CDCl 3)δ149.4,139.0(t,J＝28.7Hz),132.8(t,J＝29.6Hz),130.6,125.6(t,J＝5.5Hz),122.9,120.8(t,J＝9.2Hz),118.9(t,J＝5.9Hz),118.7(q,J＝320.7Hz).118.1(t,J＝239.6Hz).MS(FI):m/z(％)61(100),70,88,302([M] +).HRMS(EI)m/z:([M] +)Calculated for C 10H 7O 3F 5S:302.0031；Found:302.0027.
产物：
Figure PCTCN2022115642-appb-000152
微黄油状物体，66mg,74％，α/γ>50:1 19F NMR测定，硅胶色谱FP ECOFLEX C18(20g)纯化(MeCN:H 2O＝7:3) 1H NMR(400MHz,CDCl 3)δ7.73(d,J＝8.0Hz,2H),7.62(d,J＝8.0Hz,2H),6.18–6.05(m,1H),5.62–5.52(m,2H). 19F NMR(376MHz,CDCl 3)δ-95.04(d,J＝9.7Hz,2F). 13C NMR(101MHz,CDCl 3)δ140.7(t,J＝28.3Hz),132.7(t,J＝29.5Hz),132.3,126.3(t,J＝5.6Hz),120.8(t,J＝9.3Hz),118.3(t,J＝239.8Hz),118.0,114.0(t,J＝1.7Hz).MS(EI):m/z(％)75,102,152(100),179([M] +).HRMS(EI)m/z:([M] +)Calculated for C 10H 7NF 2:179.0541；Found:179.0543.
0.1mol％的CuBr加入50mL的史莱克瓶中，加入式C所示的二氟烯丙基鎓盐(6mmol,1.0equiv)，抽真空充Ar三次。加入10.0mL的THF，滴加式[C]-[Zn]所示锌试剂(1.2equiv)室温下搅拌16小时进行反应。以氟苯为内标试剂(先由 19F NMR测定α/γ＝25：1)采用 19F NMR测定产物收率，NH 4Cl淬灭反应并采用EtOAc稀释干燥，水相采用乙酸乙酯洗涤(3×10mL),有机相采用Na 2SO 4干燥，过滤，收集。硅胶色谱FP ECOFLEX C18(20g)纯化(MeCN:H 2O＝7:3)产物：
Figure PCTCN2022115642-appb-000153
827mg,77％yield,α/γ＝25:1 19F NMR测定。
产物：
Figure PCTCN2022115642-appb-000154
微黄色油状物，79mg,88％yield，α/γ>99:1 19F NMR测定，硅胶色谱FP ECOFLEX C18(20g)纯化(MeCN:H 2O＝7:3) 1H NMR(400MHz,CDCl 3)δ7.80(s,1H),7.74(d,J＝8.0Hz,2H),7.57(t,J＝7.8Hz,1H),6.20–6.04(m,1H),5.72–5.45(m,2H). 19F NMR(376MHz,CDCl 3)δ-94.37(d,J＝9.8Hz,2F). 13C NMR(126MHz,CDCl 3)δ137.8(t,J＝28.8Hz),133.5(t,J＝1.6Hz),132.7(t,J＝29.4Hz),129.8(t,J＝5.4Hz),129.5,129.3(t,J＝5.9Hz),120.9(t,J＝9.2Hz),118.1(t,J＝239.6Hz),117.9,112.9.MS(EI):m/z(％)77,102,129,152(100),179([M] +).HRMS(FI)m/z:([M] +)Calculated for C 10H 7NF 2:179.0545；Found:179.0541.
产物：
Figure PCTCN2022115642-appb-000155
黄色油状物，110.4mg,97％yield，α/γ>99:1 19F NMR测定，硅胶色谱FP ECOFLEX C18(20g)纯化(MeCN:H 2O＝7:3) 1H NMR(400MHz,CDCl 3)δ8.18(s,1H),8.12(d,J＝7.8Hz,1H),7.70(d,J＝7.8Hz,1H),7.52(t,J＝7.8Hz,1H),6.25–6.07(m,1H),5.59(dt,J＝17.2,2.8Hz,1H),5.52(d,J＝10.8Hz,1H),4.40(q,J＝7.2Hz,2H),1.41(t,J＝7.2Hz,3H). 19F NMR(376MHz,CDCl 3)δ-93.73(dd,J＝9.8,2.8Hz,2F). 13C NMR(101MHz,CDCl 3)δ165.9,136.7(t,J＝28.1Hz),133.3(t,J＝29.9Hz),131.0,130.9,129.8(t,J＝5.5Hz),128.6,126.7(t,J＝5.8Hz),120.3(t,J＝9.2Hz),118.6(t,J＝239.8Hz),61.3,14.3.MS(EI):m/z(％)133,153,181(100),226([M] +).HRMS(EI)m/z:([M] +)Calculated for C 12H 12O 2F 2:226.0800；Found:226.0806.
产物：
Figure PCTCN2022115642-appb-000156
施用1.5倍摩尔当量的式C所示的二氟烯丙基鎓盐，1倍摩尔当量的锌试剂得到微黄色油状物，113mg,87％yield，α/γ>99:1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz,CDCl 3)δ8.46–8.13(m,1H),7.70(dd,J＝8.6,2.6Hz,1H),7.49–7.44(m,2H),7.43–7.36(m,2H),7.37–7.32(m,1H),6.98–6.80(m,1H),6.24–6.09(m,1H),5.61(dt,J＝17.2,2.8Hz,1H),5.54(d,J＝10.8Hz,1H),5.42(s,2H). 19F NMR(376MHz,CDCl 3)δ-92.13(dd,J＝9.7,2.9Hz,2F). 13C NMR(101MHz,CDCl 3)δ164.6,144.8(t,J＝6.4Hz),136.9,136.3(t,J＝4.7Hz),133.3(t,J＝30.0Hz),128.5,128.0,128.0,125.4(t,J＝28.5Hz),120.3(t,J＝9.0Hz),118.8(t,J＝237.7Hz),111.1,68.0.MS(EI):m/z(％)65,91(100),138,185,265([M] +).HRMS(EI)m/z:([M] +)Calculated for C 15H 13F 2ON:261.0960；Found:261.0956.
产物：
Figure PCTCN2022115642-appb-000157
棕色固体，133.4mg，95％，α/γ>99:1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝10：1)mp:51.2-53.5℃. 1H NMR(400MHz,CDCl 3)δ8.23(d,J＝8.0Hz,1H),7.22–7.15(m,2H),7.01(t,J＝7.4Hz,1H),5.91(dq,J＝17.2,11.2Hz,1H),5.70–5.49(m,1H),5.41(d,J＝11.2,1H)4.05(t,J＝8.4Hz,2H),3.20(t,J＝8.2Hz,2H),2.44(t,J＝7.4Hz,2H),2.09–1.88(m,2H),1.85–1.73(m,2H),1.66–1.50(m,2H). 19F NMR(376MHz,CDCl 3)δ-97.67–-98.06(m,2F). 13C NMR(101MHz,CDCl 3)δ170.6,142.9,132.9(t,J＝27.5Hz),131.0,127.3,124.4,123.4,121.1(t,J＝238.4Hz),119.0(t,J＝9.5Hz),116.7,47.7,36.8(t,J＝26.5Hz),35.4,27.8,24.0,22.0(t,J＝4.3Hz).MS(EI):m/z(％)119(100),279([M] +).HRMS(EI)m/z:([M] +)Calculated for C 16H 19NOF 2([M] +):279.1429；Found:279.1430.
产物：
Figure PCTCN2022115642-appb-000158
无色油状物，124mg,97％yield，α/γ>99:1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz,CDCl 3)δ6.70(d,J＝8.4Hz,1H),6.48(d,J＝2.4Hz,1H),6.30(dd,J＝8.4,2.4Hz,1H),6.03–5.84(m,3H),5.64(d,J＝17.2Hz,1H),5.44(d,J＝10.8Hz,1H),3.92(t,J＝6.2Hz,2H),2.21–2.02(m,2H),1.97–1.88(m,2H). 19F NMR(376MHz,CDCl 3)δ-93.10–-103.05(m,2F). 13C NMR(101MHz,CDCl 3)δ154.3,148.2,141.7,132.9(t,J＝27.6Hz),121.2(t,J＝238.4Hz),119.3(t,J＝9.5Hz),107.9,105.6,101.1,98.0,67.9,33.7(t,J＝26.8Hz),22.5(t,J＝4.2Hz).MS(DART):m/z(％)138(100),256([M] +).HRMS(DART)m/z:([M+H] +)Calculated for C 13H 15F 2O 3:257.0984；Found:257.0983.
产品：
Figure PCTCN2022115642-appb-000159
棕色油状物，78.2mg,73％yield，α/γ>99:1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz,CDCl 3)δ5.97–5.81(m,1H),5.78(s,2H),5.68–5.53(m,1H),5.44(d,J＝10.8Hz,1H),3.79(t,J＝7.8Hz,2H),2.22(s,6H),2.02–1.86(m,2H),1.87–1.77(m,2H). 19F NMR(376MHz,CDCl 3)δ-97.55–-98.25(m,2F). 13C NMR(126MHz,CDCl 3)δ132.6(t,J＝27.5Hz),127.2,120.9(t,J＝239.3Hz),119.5(t,J＝9.4Hz),105.3,42.8,34.1(t,J＝27.0Hz),23.8(t,J＝3.7Hz),12.4.MS(EI):m/z(％)108(100),213([M] +).HRMS(EI)m/z:([M] +)Calculated for C 12H 17F 2N:213.1324；Found:213.1330.
产品：
Figure PCTCN2022115642-appb-000160
无色油状物，80mg,90％yield，α/γ>99:1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz,CDCl 3)δ7.68(d,J＝7.6Hz,2H),7.18(d,J＝7.6Hz,2H),5.75(dq,J＝17.4,11.2Hz,1H),5.51–5.34(m,1H),5.27(d,J＝11.2Hz,1H),3.14(t,J＝15.6Hz,2H),1.26(s,12H). 19F NMR(376MHz,CDCl 3)δ-96.39–-96.58(m,2F). 13C NMR(126MHz,CDCl 3)δ135.8(t,J＝4.4Hz),134.7,132.4(t, J＝26.9Hz),129.9,120.0(t,J＝240.6Hz),119.5(t,J＝9.2Hz),83.8,44.1(t,J＝27.5Hz),24.8.MS(FI):m/z(％)85,117,148,195(100),217,294([M] +).HRMS(FI)m/z:([M] +)Calculated for C 16H 21F 2O 2 10B:293.1633；Found:293.1638.
产品：
Figure PCTCN2022115642-appb-000161
无色油状物，66.0mg,90％yield，α/γ＝15:1 19F NMR测定，硅胶层析纯化分离(石油醚) 1H NMR(500MHz,CDCl 3)δ7.47(d,J＝7.5Hz,4H),7.37(t,J＝7.5Hz,4H),7.31(t,J＝7.5Hz,2H),5.96(dq,J＝17.2,11.1Hz,1H),5.75–5.63(m,1H),5.42(d,J＝11.1Hz,1H),4.45(t,J＝16.5Hz,1H). 19F NMR(376MHz,CDCl 3)δ-94.60–-108.06(m,2F). 13C NMR(126MHz,CDCl 3)δ137.5(t,J＝2.2Hz),132.7(t,J＝26.4Hz),129.6,128.4,127.3,120.6(t,J＝244.8Hz),120.0(t,J＝9.1Hz),58.8(t,J＝25.1Hz).MS(EI):m/z(％)152,167(100),244([M] +).HRMS(EI)m/z:([M] +)Calculated for C 16H 14F 2:244.1058；Found:244.1063.
产品：
Figure PCTCN2022115642-appb-000162
无色油状物，51.0mg,80％yield，α/γ>99:1 19F NMR测定，反相制备型HPLC纯化(MeCN:H 2O＝9:1) 1H NMR(400MHz,CDCl 3)δ7.33–7.27(m 2H),7.23–7.16(m,3H),5.86(dq,J＝17.2,11.2Hz,1H),5.68–5.56(m,1H),5.44(d,J＝11.2Hz,1H),2.81–2.75(m,1H),2.60–2.53(m,1H),2.06–1.87(m,2H),1.52–1.42(m,1H),1.07(d,J＝6.8Hz,3H). 19F NMR(376MHz,CDCl 3)δ-104.12(t,J＝12.5Hz,2F). 13C NMR(101MHz,CDCl 3)δ141.8,131.6(t,J＝27.3Hz),128.4,128.3,125.9,122.9(t,J＝241.8Hz),119.8(t,J＝9.6Hz),39.7(t,J＝24.8Hz),33.3,31.7(t,J＝3.6Hz),13.0(t,J＝4.8Hz).MS(EI):m/z(％)91(100),131,210([M] +).HRMS(EI)m/z:([M] +)Calculated for C 13H 16F 2:210.1220；Found:210.1215.
产品：
Figure PCTCN2022115642-appb-000163
黄色油状物，112.3mg,79％yield，α/γ>99:1 19F NMR测定，反相制备型HPLC(MeCN:H 2O＝6:4) 1H NMR(400MHz,CDCl 3)δ7.98(d,J＝8.8Hz,2H),6.92(d,J＝8.8Hz,2H),5.89(dq,J＝17.4,11.3Hz,1H),5.71–5.61(m,1H),5.48(d,J＝11.3Hz,1H),4.50–4.23(m,2H),2.26–2.06(m,2H),1.64–1.52(m,1H),1.09(d,J＝6.8Hz,3H). 19F NMR(376MHz,CDCl 3)δ-103.74(dt,J＝241.3,11.6Hz,1F),-105.56(dt,J＝241.3,13.0Hz,1F). 13C NMR(101MHz,CDCl 3)δ166.2,163.4,131.5,131.3(t,J＝27.2Hz),122.6,122.5(t,J＝242.0Hz),120.2(t,J＝9.5Hz),113.6,62.3,55.4,37.4(t,J＝25.4Hz),29.2(t,J＝4.1Hz),13.1(t,J＝4.7Hz).MS(EI):m/z(％)135(100),152,284([M] +).HRMS(EI)m/z:([M] +)Calculated for C 13H 16F 2:284.1219；Found:284.1225.
产品：
Figure PCTCN2022115642-appb-000164
黄色油状物，83mg,60％yield，α/γ>99:1 19F NMR测定，硅胶色谱纯化分离(石油醚：乙酸乙酯＝1：1) 1H NMR(400MHz,CDCl 3)diastereomer mixtures: 1H NMR(400MHz,CDCl3)δ5.84(m,1H),5.64–5.54(m,1H),5.45–5.38(m,1H),4.46–4.40(m,0.86H)(4.38(dd,J＝8.4,2.7Hz,0.14H)),3.67(s,3H),3.65–3.54(m,1H),3.54–3.43(m,1H),2.68–2.53(m,2H),2.22–2.08(m,2H),2.00–1.87(m,2H),1.02(t,J＝6.7Hz,3H). 19F NMR(376MHz,CDCl 3)非对映异构体混合物:δ-103.76(dtd,J＝240.6,11.0,2.6Hz,0.46F)(-103.42(dtd,J＝240.8,11.0,2.6Hz,0.07F)),-104.22(dtd,J＝240.7,11.7,2.6Hz,0.39F)(-104.49(dtd,J＝241.5,12.2,2.4Hz,0.07F)),-107.36–-108.84(m,0.85F)(-107.50–-109.05(m,0.15F)). 13C NMR(126MHz,CDCl 3)非对映异构体混合物:δ172.64(172.62),169.8(169.6),131.6(t,J＝27.1Hz)(131.5(t,J＝27.1Hz)),122.21(t,J＝241.9Hz)(122.16(t,J＝242.0Hz)),120.0(t,J＝9.6Hz)(119.9(t,J＝9.6Hz)),58.64(58.59),52.0,47.0(46.9),36.9(t,J＝25.2Hz)(36.5(t,J＝25.2Hz)),34.6(t,J＝3.7Hz)(34.4(t,J＝3.8Hz)),29.07(28.99),24.61(24.58),13.51(t,J＝3.9Hz)(13.48(t,J＝3.9Hz)).MS(EI):m/z(％)70(100),216,275([M] +).HRMS(EI)m/z:([M] +)Calculated for C 13H 19O 3NF 2:275.1328；Found:275.1331.产品：
Figure PCTCN2022115642-appb-000165
微黄色油状物，110.9mg,85％yield，α/γ>99:1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝10:1) 1H NMR(400MHz,CDCl 3)δ5.81(dq,J＝17.2,11.2Hz,1H),5.57(dt,J＝17.2,2.6Hz,1H),5.43(d,J＝11.2Hz,1H),4.26–3.95(m,2H),2.71–2.47(m,2H),1.99–1.80(m,1H),1.77–1.67(m,2H),1.41(s,9H),1.36–1.24(m,2H). 19F NMR(376MHz,CDCl 3)δ-104.5--107.2(m,2F). 13C NMR(126MHz,CDCl 3)δ154.5,131.2(t,J＝27.2Hz),121.5(t,J＝241.4Hz),120.1(t,J＝9.5Hz),79.5,43.1(t,J＝25.8Hz),28.3,24.9.MS(ESI):m/z(％)162(100),284([M+Na] +).HRMS(ESI)m/z:([M+Na] +)Calculated for C 13H 21O 2NF 2Na:284.1433；Found:284.1428.
产品：
Figure PCTCN2022115642-appb-000166
无色油状物，56mg,74％yield，α/γ>50:1 19F NMR测定，硅胶色谱纯化分离(石油醚100％) 1H NMR(500MHz,CDCl 3)δ7.32(d,J＝8.5Hz,2H),7.24(d,J＝8.5Hz,2H),5.59(dq,J＝17.3,10.5Hz,1H),5.45–5.37(m,1H),5.23(d,J＝11.0Hz,1H),2.37(dd,J＝16.5,9.0Hz,1H),1.75–1.63(m,1H),1.47–1.36(m,1H),1.34(s,9H),1.21–1.13(m,1H). 19F NMR(376MHz,CDCl 3)δ-90.04(dt,J＝251.0,10.2Hz),-95.59(dt,J＝251.4,12.4Hz). 13C NMR(126MHz,CDCl 3)δ149.2,133.3,133.0(t,J＝28.7Hz),129.3(t,J＝1.6Hz),124.7,120.5(dd,J＝239.0,236.9Hz),118.4(t,J＝9.3Hz),34.4,31.4,23.6(dd,J＝32.1,30.3Hz),20.3(dd,J＝3.9,1.9Hz),5.7(dd,J＝4.9,2.6Hz).MS(EI):m/z(％)45,70(100),159,250([M] +).HRMS(EI) m/z:([M] +)Calculated for C 16H 20F 2:250.1528；Found:250.1534.
产品：
Figure PCTCN2022115642-appb-000167
1H NMR(600MHz,DMSO-d6)δ5.78(dq,J＝17.4,11.9Hz,1H),5.33(ddt,J＝17.3,2.5,1.3Hz,1H),5.22(d,J＝11.1Hz,1H),0.78(s,9H). 19F NMR(565MHz,DMSO-d 6)δ-112.20(d,J＝12.0Hz,2F).MS(FI):m/z(％)134(100)([M] +)；HRMS(FI)m/z:([M] +)Calculated for C 7H 12F 2:134.0902；Found:134.0903.
产品：
Figure PCTCN2022115642-appb-000168
黄色液体，131mg,85％yield，α/γ>11:1， 19F NMR测定，硅胶色谱纯化分离(石油醚100％) 1H NMR(400MHz,CDCl 3)δ7.68(d,J＝8.4Hz,2H),7.66–7.60(m,4H),7.53–7.45(m,2H),7.44–7.37(m,1H),6.28–6.24(m,1H),5.97–5.92(m,1H). 19F NMR(376MHz,CDCl 3)δ-93.08(s,2F). 13C NMR(126MHz,CDCl 3)δ143.4,140.0,132.9(t,J＝27.4Hz),128.9,127.9,127.2,127.1,126.9(t,J＝34.7Hz),126.4(t,J＝5.5Hz),122.5(t,J＝5.9Hz),117.7(t,J＝243.8Hz).MS(EI):m/z(％)152,203(100),308([M] +).HRMS(EI)m/z:([M] +)Calculated for C 15H 11F 2Br:308.0007；Found:308.0013.
产品：
Figure PCTCN2022115642-appb-000169
微黄色油状物，97mg,63％yield,α/γ＝3：1由 19F NMR测定，当采用0.6倍当量催化剂时，产物140mg，92％yield,α/γ＝50：1，硅胶色谱纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz,CDCl 3)δ7.43–7.28(m,5H),6.27–6.25(m,1H),5.86–5.85(m,1H),4.53(s,2H),3.54(t,J＝6.4Hz,2H),2.34–2.16(m,2H),1.91–1.74(m,2H). 19F NMR(376MHz,CDCl 3)δ-98.22(t,J＝16.3Hz,2F). 13C NMR(101MHz,CDCl 3)δ138.2,128.4,127.58,127.56,125.5(t,J＝31.7Hz),121.1(t,J＝6.6Hz),120.1(t,J＝244.6Hz),72.8,69.0,32.1(t,J＝25.9Hz),22.6(t,J＝4.1Hz).MS(FI):m/z(％)187(100),304([M] +).HRMS(FI)m/z:([M] +)Calculated for C 13H 15F 2OBr:304.0269；Found:304.0273.
产品：
Figure PCTCN2022115642-appb-000170
微黄色油状物，当采用0.6倍当量催化剂时，76.5mg,98％yield,α/γ＝50：1由 19F NMR测定。 1H NMR(400MHz,CDCl 3)δ7.39–7.28(m,5H),5.84–5.83(m,1H),5.61–5.60(m,1H),4.53(s,2H),3.53(t,J＝6.3Hz,2H),2.27–2.15(m,2H),1.82–1.75(m,2H). 19F NMR(376MHz,CDCl 3)δ-99.9(t,J＝16.4Hz,2F). 13C NMR(101MHz,CDCl 3)δ138.3,135.0(t,J＝32.1Hz),128.4,127.60,127.59,120.0(t,J＝244.4Hz),116.4(t,J＝5.9Hz),72.9,69.0,31.7(t,J＝25.8Hz),22.6(t,J＝4.2Hz).
产品：
Figure PCTCN2022115642-appb-000171
无色油状物，160.9mg,96％yield，α/γ>99：1硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz,CDCl 3)δ6.70(d,J＝8.4Hz,1H),6.49(d,J＝2.4Hz,1H),6.31(dd,J＝8.4,2.4Hz,1H),6.29–6.26(m,1H),5.91(s,2H),5.88–5.85(m,1H),3.93(t,J＝6.2Hz,2H),2.38–2.22(m,2H),1.97–1.86(m,2H). 19F NMR(376MHz,CDCl 3)δ-98.34(t,J＝16.2Hz,2F). 13C NMR(101MHz,CDCl 3)δ154.2,148.2,141.7,125.4(t,J＝31.5Hz),121.2(t,J＝6.6Hz),120.0(t,J＝244.8Hz),107.9,105.6,101.1,98.1,67.6,32.0(t,J＝26.1Hz),22.3(t,J＝4.1Hz).MS(EI):m/z(％)138(100),334([M] +).HRMS(EI)m/z:([M] +)Calculated for C 13H 13F 2O 3Br:334.0011；Found:334.0008.
产品：
Figure PCTCN2022115642-appb-000172
无色油状物，100mg,90％yield，α/γ>99：1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1)，使用0.6倍当量催化剂CuBr， 1H NMR(400MHz,CDCl 3)δ6.29–6.25(m,1H),5.90–5.85(m,1H),2.44(t,J＝7.2Hz,2H),2.34–2.17(m,2H),1.85(p,J＝7.2Hz,2H). 19F NMR(376MHz,CDCl 3)δ-98.65(t,J＝16.0Hz). 13C NMR(101MHz,CDCl 3)δ124.7(t,J＝31.2Hz),121.6(t,J＝6.7Hz),119.3(t,J＝245.4Hz),118.6,34.0(t,J＝26.3Hz),18.5(t,J＝4.3Hz),16.7.MS(FI):m/z(％)144,223(100)([M] +).HRMS(FI)m/z:([M] +)Calculated for C 7H 8F 2NBr:222.9803；Found:222.9805.
产品：
Figure PCTCN2022115642-appb-000173
微黄色油状物，71mg,97％yield，α/γ>99：1 19F NMR测定，硅胶色谱纯化分离(石油醚/DCM＝20:1)， 1H NMR(400MHz,CDCl 3)δ7.46–7.40(m,2H),7.39–7.33(m,3H),5.76(s,1H),5.50(s,1H),3.48(t,J＝6.8Hz,2H),2.02–1.85(m,2H),1.74(p,J＝6.8Hz,2H),1.65–1.54(m,2H). 19F NMR(376MHz,CDCl 3)δ-95.99(t,J＝16.2Hz,2F). 13C NMR(101MHz,CDCl 3)144.6(t,J＝22.8Hz),136.9,128.4,128.2,128.1,122.3(t,J＝243.1Hz),118.2(t,J＝9.0Hz),44.4,35.4(t,J＝26.4Hz),31.9,19.7(t,J＝4.3Hz).MS(FI):m/z(％)194,244(100)([M] +).HRMS(EI)m/z:([M] +)Calculated for C 13H 15F 2Cl:244.0825；Found:244.0828.
产品：
Figure PCTCN2022115642-appb-000174
黄色油状物，89mg,99％yield，α/γ>99：1 19F NMR测定，硅胶色谱纯化分离(石油醚)， 1H NMR(400MHz,CDCl 3)δ7.37(d,J＝8.8Hz,2H),7.34(d,J＝8.8Hz,2H).,5.70(s,1H),5.48(s,1H),3.48(t,J＝6.6Hz,2H),2.00–1.86(m,2H),1.80–1.70(m,2H),1.64–1.52(m,2H),1.34(s,9H). 19F NMR(376MHz, CDCl 3)δ-95.97(t,J＝16.3Hz,2F). 13C NMR(101MHz,CDCl 3)δ151.3,144.4(t,J＝23.1Hz),133.9,127.7,125.3,122.5(t,J＝243.1Hz),117.6(t,J＝9.0Hz),44.5,35.5(t,J＝26.5Hz),34.5,31.9,31.3,19.8(t,J＝4.3Hz).MS(FI):m/z(％)57,128,285(100),300([M +]).HRMS(FI)m/z:([M] +)Calculated for C 17H 23F 2Cl([M +]):300.1451；Found:300.1450.
产品：
Figure PCTCN2022115642-appb-000175
微黄色油状物，90mg,95％yield，α/γ>99：1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1)， 1H NMR(400MHz,CDCl 3)δ8.03(d,J＝8.2Hz,2H),7.48(d,J＝8.2Hz,2H),5.82(s,1H),5.55(s,1H),4.39(q,J＝7.2Hz,2H),3.47(t,J＝6.4Hz,2H),1.99–1.82(m,2H),1.78–1.68(m,2H),1.63–1.53(m,2H),1.40(t,J＝7.2Hz,3H). 19F NMR(376MHz,CDCl 3)δ-95.84(t,J＝16.1Hz,2F). 13C NMR(101MHz,CDCl 3)δ166.2,144.0(t,J＝23.5Hz),141.3,130.3,129.6,128.0,122.0(t,J＝243.2Hz),119.4(t,J＝8.9Hz),61.1,44.4,35.4(t,J＝26.2Hz),31.8,19.7(t,J＝4.3Hz),14.3.MS(FI):m/z(％)133,151,181,198(100),316([M +]).HRMS(FI)m/z:([M] +)Calculated for C 16H 19F 2O 2Cl([M +]):316.1036；Found:316.1033.产品：
Figure PCTCN2022115642-appb-000176
黄色油状物，57mg,72％yield，α/γ>99：1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝50:1)，0.6倍当量CuBr使用， 1H NMR(400MHz,CDCl 3)δ7.72(d,J＝8.0Hz,2H),7.60(d,J＝8.0Hz,2H),6.04–5.91(m,1H),5.82–5.70(m,1H),2.17–2.05(m,2H),1.46–1.34(m,2H),1.35–1.18(m,6H),0.87(t,J＝6.6Hz,3H). 19F NMR(376MHz,CDCl 3)(Z)δ-86.40(d,J＝13.6Hz),(E)-91.71(dd,J＝10.0,3.3Hz). 13C NMR(126MHz,CDCl 3)δ141.6(t,J＝28.7Hz),138.4(t,J＝8.9Hz),132.2,126.4(t,J＝5.5Hz),125.0(t,J＝28.7Hz),118.7(t,J＝238.6Hz),118.1,113.8,31.8,31.5,28.7,28.2,22.5,14.0.MS(DART):m/z(％)185,264([M+H] +).HRMS(DART)m/z:([M+H] +):Calculated for C 16H 20F 2N:264.1558；Found:264.1556.产品：
Figure PCTCN2022115642-appb-000177
微黄色油状物，67mg,65％yield，α/γ>99：1 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝50:1)，0.6倍当量CuBr使用， 1H NMR(400MHz,CDCl 3)δ6.70(d,J＝8.4Hz,1H),6.48(d,J＝2.4Hz,1H),6.31(dd,J＝8.4,2.4Hz,1H),6.14–6.03(m,0.55H),5.91(s,2H),5.81–5.67(m,0.45H),5.65–5.37(m,1H),3.96–3.88(m,2H),2.34–2.01(m,4H),2.02–1.86(m,2H),1.46–1.36(m,2H),1.36–1.24(m,6H),0.89(t,J＝6.4Hz,3H). 19F NMR(376MHz,CDCl 3)δ-91.00(q,J＝15.7Hz,0.9F),-94.84–-95.01(m,1.1F). 13C NMR(101MHz,CDCl 3)δ154.3,148.2,141.7,138.5(t,J＝6.1Hz)(136.3(t,J＝9.0Hz)),124.9(t,J＝24.5Hz Hz)(124.4(t,J＝25.1Hz Hz)),122.5(t,J＝239.0Hz)(121.50(t,J＝237.9Hz)),107.9,105.6,101.1,98.1,68.0,35.2(t,J＝27.4Hz)(34.13(t,J＝27.4Hz)),31.8,31.62(31.60),29.3,28.9(28.8),28.3(28.4), 22.6(22.5),14.0(括号中是异构体数据).MS(DART):m/z(％)322(100),341([M +]).HRMS(DART)m/z:([M+H] +)Calculated for C 19H 27F 2O 3:341.1923Found:341.1920
产品：
Figure PCTCN2022115642-appb-000178
微黄色油状物，64mg,51％yield，α/γ>99：1 19F NMR测定，硅胶层析纯化分离(石油醚)，0.6倍当量CuBr使用， 1H NMR(400MHz,CDCl 3)δ6.13–5.98(m,0.8H),5.80–5.67(m,0.2H),5.60–5.37(m,1H),3.54(t,J＝6.5Hz,2H),2.30–2.18(m,0.4H),2.14–2.06(m,1.6H),2.00–1.78(m,4H),1.70–1.54(m,2H),1.47–1.34(m,2H),1.34–1.22(m,6H),0.89(t,J＝6.8Hz,3H). 19F NMR(376MHz,CDCl 3)δ-90.74(q,J＝14.9Hz,0.4F),-93.83–-95.92(m,1.6F). 13C NMR(101MHz,CDCl 3)δ138.5(t,J＝6.1Hz),136.3(t,J＝9.1Hz),124.75(t,J＝26.5Hz)(124.30(t,J＝27.1Hz)),121.4(t,J＝237.9Hz),44.6,36.7(t,J＝27.2Hz),32.1,31.8,31.6,28.8,28.5,22.6,20.0(t,J＝4.3Hz),14.1.MS(FI):m/z(％)232(100),252([M] +).HRMS(FI)m/z:([M] +)Calculated for C 13H 23F 2Cl:252.1451；Found:252.1454.
产品：
Figure PCTCN2022115642-appb-000179
微黄色油状物(108.6mg,96％yield,)硅胶色谱纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz,Chloroform-d)δ7.40–7.27(m,5H),5.91(dq,J＝17.3,10.9Hz,1H),5.62(dt,J＝17.4,2.7Hz,1H),5.42(d,J＝11.0Hz,1H),4.51(s,2H),3.52(t,J＝6.2Hz,2H),2.12–1.94(m,2H),1.86–1.73(m,H). 19F NMR(376MHz,Chloroform-d)δ-97.92–-98.22(m,2F). 13C NMR(126MHz,Chloroform-d)δ138.32,132.93(t,J＝27.5Hz),128.37,127.59,121.30(t,J＝238.4Hz),119.15(t,J＝9.5Hz),72.85,69.33,33.90(t,J＝26.8Hz),22.77(t,J＝4.2Hz).MS(EI):m/z(％)91(100),226(M +).HRMS:Calculated for C 13H 16OF 2:226.1167；Found:226.1164.
将0.5mol％的CuBr加入50mL的史莱克瓶中，加入式C所示的二氟烯丙基鎓盐(4.2mmol,1.0equiv)，抽真空充Ar三次。加入10.0mL的THF，滴加式[C]-[Zn]所示锌试剂(1.2equiv)室温下搅拌16小时进行反应。以氟苯为内标试剂(先由 19F NMR测定α/γ＝10：1)采用 19F NMR测定产物收率，NH 4Cl淬灭反应并采用EtOAc稀释干燥，水相采用乙酸乙酯洗涤(3×10mL),有机相采用Na 2SO 4干燥，过滤，收集。
克级反应所得产品：
Figure PCTCN2022115642-appb-000180
微黄油状物，676.3mg，81％yeild，硅胶色谱纯化分离(DCM:PE＝1:5)。
产品：
Figure PCTCN2022115642-appb-000181
无色油状物(79.7mg,90％yield,)硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz, Chloroform-d)δ7.68(d,J＝7.7Hz,2H),7.18(d,J＝7.7Hz,2H),5.75(dq,J＝17.4,11.1Hz,1H),5.51–5.34(m,1H),5.27(dt,J＝11.0,0.8Hz,1H),3.14(t,J＝15.6Hz,2H),1.26(s,12H). 19F NMR(376MHz,Chloroform-d)δ-96.49(ddd,J＝16.7,14.0,10.2Hz,2F). 13C NMR(126MHz,Chloroform-d)δ135.83(t,J＝4.4Hz),134.73,132.36(t,J＝26.9Hz),129.92,120.03(t,J＝240.6Hz),119.54(t,J＝9.2Hz),83.78,44.10(t,J＝27.5Hz),24.84.MS(EI):m/z(％)294(M+).HRMS:Calculated for C16H21F210B:293.1638；Found:293.1633.
产品：
Figure PCTCN2022115642-appb-000182
无色油状物(44.0mg,90％yield)，硅胶层析纯化分离(石油醚) 1H NMR(400MHz,Chloroform-d)δ7.29(m 2H),7.23–7.16(m,3H),5.86(dq,J＝17.4,11.5Hz,1H),5.68–5.56(m,1H),5.44(d,J＝11.0Hz,1H),2.77(ddd,J＝14.8,10.1,5.3Hz,1H),2.56(ddd,J＝13.8,10.1,6.6Hz,1H),2.06–1.87(m,2H),1.47(ddt,J＝13.5,9.8,4.8Hz,1H),1.07(d,J＝6.8Hz,3H). 19F NMR(376MHz,Chloroform-d)δ-104.12(t,J＝12.5Hz,2F). 13C NMR(101MHz,Chloroform-d)δ141.78,131.57(t,J＝27.3Hz),128.41,128.34,125.93,122.88(t,J＝241.8Hz),119.77(t,J＝9.6Hz),39.65(t,J＝24.8Hz),33.27,31.70(t,J＝3.6Hz),13.00(t,J＝4.8Hz).MS(EI):m/z(％)91(100),210(M+).HRMS:Calculated for C 13H 16F 2:210.1220；Found:210.1215.
产品：
Figure PCTCN2022115642-appb-000183
橙色油状物，48.1mg,82％yield,α/γ＝50：1由 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz,Chloroform-d)δ6.27(dd,J＝2.3,1.2Hz,1H),5.87(dd,J＝2.4,1.2Hz,1H),5.80(s,2H),3.94–3.72(m,2H),2.25(s,6H),2.23–2.07(m,2H),1.80(tt,J＝10.5,6.7Hz,2H). 19F NMR(376MHz,Chloroform-d)δ-98.06(t,J＝16.0Hz,2F). 13C NMR(101MHz,Chloroform-d)δ127.17,124.95(t,J＝31.4Hz),121.43(t,J＝6.7Hz),119.85(t,J＝245.2Hz),105.37,42.62,32.40(t,J＝26.2Hz),23.74(t,J＝3.7Hz),12.42.MS(FI):m/z(％)138(100),291([M] +).HRMS:Calculated for C 12H 16NF 2Br([M] +):291.0431；Found:291.0429.
上述产品
Figure PCTCN2022115642-appb-000184
可进一步用于偶联反应制备
Figure PCTCN2022115642-appb-000185
反应如下所示：
Figure PCTCN2022115642-appb-000186
将Pd(PPh 3) 4(8.6mg,5mol％)加入25mL的史莱克瓶中，加入式CuI(2.8mg,10mol％)，抽真空 充Ar三次。氩气保护下加入化合物
Figure PCTCN2022115642-appb-000187
(45.7mg,0.15mmol,1.0equiv),干二异丙基乙基胺EtN(i-Pr) 2(52.2μL,0.3mmol,2.0equiv)和苯乙炔(16.1μL,0.15mmol,1.0equiv)，反应混合液中加入20ml DMF，于搅拌下40℃反应24h。冷却至室温，加水用丙烯酸乙酯萃取分液，有机相用饱和食盐水(brine)洗涤Na 2SO 4干燥，减压蒸馏干燥，以FP ECOFLEX C18(20g)色谱纯化得化合物
Figure PCTCN2022115642-appb-000188
34mg,70％yield， 1H NMR(400MHz,CDCl 3)δ7.50–7.45(m,2H),7.39–7.27(m,8H),5.95–5.90(m,1H),5.82–5.78(m,1H),4.52(s,2H),3.56(t,J＝6.4Hz,2H),2.35–2.19(m,2H),1.91–1.80(m,2H). 19F NMR(376MHz,CDCl 3)δ-99.31(t,J＝16.4Hz,2F). 13C NMR(126MHz,CDCl 3)δ138.3,131.7,128.8,128.3,128.2,128.1(t,J＝28.8),127.6,127.5,124.1(t,J＝6.9Hz),122.2,120.8(t,J＝244.1Hz),92.1,84.4(t,J＝4.3Hz),72.8,69.3,33.0(t,J＝26.1Hz),22.7(t,J＝4.2Hz).MS(FI):m/z(％)91(100),129,235,326([M] +).HRMS(FI)m/z:([M] +)Calculated for C 21H 19F 2O:326.1477；Found:326.1475.
产品：
Figure PCTCN2022115642-appb-000189
微黄色油状物(52.5mg,83％yield)，硅胶层析纯化分离(石油醚100％) 1H NMR(400MHz,Chloroform-d)δ7.46(d,J＝8.9Hz,2H),7.41(d,J＝8.5Hz,2H),7.21(t,J＝7.9Hz,1H),6.99–6.92(m,1H),6.90–6.81(m,2H),5.71(td,J＝1.8,1.0Hz,1H),5.65(s,1H),3.74(s,3H),1.33(s,9H). 19F NMR(376MHz,Chloroform-d)δ-90.08(s,2F). 13C NMR(101MHz,Chloroform-d)δ159.15,153.04(t,J＝1.7Hz),145.40(t,J＝26.6Hz),137.90,133.40(t,J＝27.6Hz),129.08,125.66(t,J＝5.5Hz),125.21,120.74,120.57(t,J＝241.8Hz),119.39(t,J＝8.0Hz),113.85,113.68,55.10,34.71,31.20.MS(FI):m/z(％)316(100),316([M] +).HRMS:Calculated for C 20H 22F 2:316.1629；Found:316.1633.
产品：
Figure PCTCN2022115642-appb-000190
微黄色油状物，54.2mg,76％yield,α/γ＝25:1由 19F NMR测定，硅胶层析纯化分离(石油醚) 1H NMR(400MHz,Chloroform-d)δ7.26(t,J＝8.0Hz,1H),7.00(ddd,J＝7.7,1.8,1.0Hz,1H),6.96(t,J＝2.1Hz,1H),6.88(ddd,J＝8.2,2.7,0.9Hz,1H),5.73(dt,J＝1.8,1.0Hz,1H),5.48(q,J＝1.2Hz,1H),3.81(s,3H),3.56(t,J＝6.3Hz,2H),2.09–1.90(m,2H),1.69–1.55(m,2H),0.84(s,9H),-0.01(s,6H). 19F NMR(376MHz,Chloroform-d)δ-95.65(t,J＝16.6Hz,2F). 13C NMR(101MHz,Chloroform-d)δ159.38,144.70(t,J ＝23.3Hz),138.41,129.31,122.66(t,J＝242.7Hz),120.58,118.03(t,J＝8.9Hz),113.57,62.12,55.19,32.80(t,J＝26.4Hz),25.83,18.19,-5.43.MS(FI):m/z(％)356(100),356(M +).HRMS:Calculated for C 19H 30F 2O 2Si:356.1984；Found:356.1978.
产品：
Figure PCTCN2022115642-appb-000191
微黄色油状物(27.9mg,73％yield),硅胶层析纯化分离(石油醚) 1H NMR(400MHz,Chloroform-d)δ7.35(s,4H),5.72–5.62(m,1H),5.46(s,1H),3.56(t,J＝6.2Hz,2H),1.98(tt,J＝16.4,8.2Hz,2H),1.71–1.49(m,2H),1.32(s,9H),0.82(s,9H),-0.02(s,6H). 19F NMR(376MHz,Chloroform-d)δ-95.71(t,J＝16.6Hz,2F). 13C NMR(101MHz,Chloroform-d)δ151.12,144.61(t,J＝23.2Hz),134.01,125.21,127.70,128.82–122.39(m),117.37(t,J＝8.9Hz),62.13,34.52,32.86(t,J＝26.4Hz),31.26,25.85,18.20,-0.02,-5.41.MS(FI):m/z(％)325(100),382(M +).HRMS:Calculated for C 22H 36F 2OSi:382.2504；Found:382.2498.产品：
Figure PCTCN2022115642-appb-000192
微黄色油状物(74mg,90％yield),硅胶层析纯化分离(石油醚) 1H NMR(400MHz,Chloroform-d)δ7.35(d,J＝8.8Hz,2H),6.88(d,J＝8.8Hz,2H),5.67(s,1H),5.43(s,1H),3.82(s,3H),3.47(t,J＝6.4Hz,2H),2.00–1.83(m,2H),1.79–1.68(m,2H),1.62–1.50(m,2H). 19F NMR(376MHz,Chloroform-d)δ-95.97(t,J＝16.1Hz,2F). 13C NMR(101MHz,Chloroform-d)δ159.6,144.0(t,J＝23.0Hz),129.27,129.25,122.5(t,J＝243.0Hz),117.1(t,J＝9.1Hz),113.7,55.2,44.5,35.4(t,J＝26.5Hz),31.9,19.8(t,J＝4.3Hz).
产品：
Figure PCTCN2022115642-appb-000193
黄色油状物，94mg,66％yield,E/Z＝4.6:1,γ/α>99:1， 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝1:1)，0.6倍当量CuBr使用， 1H NMR(400MHz,CDCl 3)δ8.07(d,J＝8.4Hz,2H),7.55(d,J＝8.4Hz,0.30H)(7.60(d,J＝8.4Hz,1.70H),6.00–5.87(m,1H),5.86–5.70(m,1H),4.40(t,J＝6.2Hz,2H),2.85(t,J＝6.2Hz,2H),2.63(q,J＝6.8Hz,4H),2.16–2.01(m,2H),1.45–1.32(m,2H),1.31–1.21(m,6H),1.06(t,J＝7.2Hz,6H),0.86(t,J＝6.8Hz,3H). 19F NMR(376MHz,CDCl 3)δ-85.78(d,J＝12.7Hz,0.28F),-91.12(d,J＝9.2Hz,1.72F). 13C NMR(126MHz,CDCl 3)δ165.9,141.4(t,J＝28.2Hz),137.9(t,J ＝8.9Hz),131.4,129.6,125.6(t,J＝5.4Hz),125.5(t,J＝29.0Hz),119.3(t,J＝237.9Hz),63.4,50.9,47.8,31.8,31.5,28.7,28.2,22.5,14.0,11.8.MS(DART):m/z(％)382(100)([M+H] +).HRMS(DART)m/z:([M+H] +)Calculated for C 19H 27F 2O 3:382.2552；Found:382.2550.
应用实施例3
步骤(1)2.5mol％的CuBr加入25mL的史莱克瓶中，加入式C所示的二氟烯丙基鎓盐(0.5mmol,1.0equiv)，抽真空充Ar三次。加入2.0mL的THF，滴加式[C]-[Zn]所示锌试剂(1.2equiv)室温下搅拌3小时进行反应。以氟苯为内标试剂采用 19F NMR测定产物收率，NH 4Cl淬灭反应并采用EtOAc稀释干燥，水相采用乙酸乙酯洗涤(3×10mL),有机相采用Na 2SO 4干燥，过滤，收集。色谱纯化后产品直接用于下一步制备。
步骤(2)：25℃下，25mL烧瓶中加入K 2OsO 2(OH) 4(9.2mg,5mol％)，NMO(135mg,1mmol,2.0equiv)与上述所得化合物搅拌24h，乙酸乙酯稀释，用饱和NaHCO 3、盐水洗涤，用Na 2SO 4干燥，过滤并浓缩。硅胶色谱纯化得下述产物。
步骤(1)：
Figure PCTCN2022115642-appb-000194
步骤(2)：
Figure PCTCN2022115642-appb-000195
产品如下所示：
产品：
Figure PCTCN2022115642-appb-000196
粘稠黄色油状物，203mg,85％yield，α/γ＝99：1由 19F NMR测定，dr＝1:1)，硅胶层析纯化分离(石油醚/乙酸乙酯＝100:1) 1H NMR(400MHz,CDCl 3)δ8.08(d,J＝8.2Hz,2H),7.60(d,J＝8.2Hz,2H),5.94(d,J＝3.6Hz,1H),5.50(d,J＝2.8Hz,1H),4.62(d,J＝3.6Hz,1H),4.41–4.27(m,2H),4.17–4.02(m,3H),3.84–3.65(m,2H),3.19(t,J＝6.2Hz,1H),2.22(s,1H),1.55(s,3H),1.41(s,3H),1.32(s,3H),1.26(s,3H). 19F NMR(376MHz,CDCl 3)δ-105.10(dd,J＝255.5,8.3Hz,0.5F),-105.23(dd,J＝255.5,8.4Hz,0.5F),-110.67(dd,J＝255.5,13.4Hz,1F). 13C NMR(101MHz,CDCl 3)δ164.5,139.2(t,J＝25.7Hz),131.2,129.7,126.1(t,J＝6.4Hz),120.4(t,J＝248.6Hz),112.4,109.5,105.0,83.3,79.8,76.9,73.9(t,J＝29.7Hz),72.5,67.2,60.9,26.8,26.6,26.1,25.1.MS(DART):m/z(％)274,417(100),475([M+H] +).HRMS(DART) m/z:([M+H] +)Calculated for C 22H 29F 2O 9:475.1774；Found:475.1771.
产品：
Figure PCTCN2022115642-appb-000197
黄色粘稠油状物(150mg,71％yield,两步，α/γ＝99：1由 19F NMR测定，dr＝1:1)，硅胶层析纯化分离(石油醚/乙酸乙酯＝1:1) 1H NMR(400MHz,CDCl 3)δ5.85(d,J＝3.6Hz,1H),4.51(d,J＝4.0Hz,1H),4.28(q,J＝6.4Hz,1H),4.11(dd,J＝7.4,3.0Hz,1H),4.05(dd,J＝8.6,6.2Hz,1H),3.96(dd,J＝8.8,6.0Hz,1H),3.83(d,J＝3.2Hz,1H),3.81–3.72(m,3H),3.63–3.55(m,1H),3.54–3.46(m,1H),3.33(s,1H),2.57(s,1H),2.03–1.78(m,2H),1.63–1.49(m,4H),1.47(s,3H),1.43–1.37(m,5H),1.33(s,3H),1.30(s,3H). 19F NMR(376MHz,CDCl 3)δ-108.22–-109.84(m,1F),-110.86–-112.38(m,1F). 13C NMR(126MHz,CDCl 3)δ123.7(t,J＝244.4Hz),111.7,108.9,105.1,82.3,82.0,81.0,72.6(dd,J＝29.8,27.4Hz),72.4,70.2,67.0,61.0(t,J＝4.0Hz),32.8(t,J＝23.9Hz),29.3,26.7,26.6,26.1,25.8,25.2,21.0(t,J＝4.3Hz).MS(FI):m/z(％)101(100),425([M-CH 3] +).HRMS(FI)m/z:([M+H] +)Calculated for C 20H 35F 2O 8([M+H] +):441.2295；Found:441.2301.
产品：
Figure PCTCN2022115642-appb-000198
棕色固体，127mg,60％yield,两步，α/γ＝99：1由 19F NMR测定，dr＝1:1，硅胶层析纯化分离(石油醚/乙酸乙酯＝1:1) 1H NMR(400MHz,CDCl 3)δ7.19(d,J＝8.6Hz,1H),6.70(d,J＝8.6Hz,1H),6.64(s,1H),3.98(t,J＝6.0Hz,2H),3.92–3.76(m,3H),2.98–2.82(m,2H),2.50(dd,J＝18.9,8.6Hz,1H),2.43–2.34(m,1H),2.29–1.89(m,9H),1.67–1.32(m,5H),1.30–1.20(m,1H),0.90(s,3H). 19F NMR(376MHz,CDCl 3)δ-107.13–-110.53(m,1F),-111.62--112.72(m,1F). 13C NMR(101MHz,CDCl 3)δ221.3,156.8,137.8,132.2,126.3,123.8(t,J＝245.7Hz),114.6,112.1,77.2,72.6(dd,J＝30.3,27.2Hz),67.0,61.0(t,J＝3.9Hz),50.4,48.0,43.9,38.3,35.9,31.5,29.9(t,J＝21.1Hz),29.6,26.5,25.9,21.6,13.8.MS(ESI):m/z(％)55(100),74,185,270,422([M] +).HRMS(ESI)m/z:([M+Na] +)Calculated for C 24H 32F 2O 4Na:445.2161；Found:445.2156.
应用实施例4
2.5mol％的CuBr加入25mL的史莱克瓶中，加入式C所示的二氟烯丙基鎓盐(0.5mmol,1.0equiv)，抽真空充Ar三次。加入2.0mL的THF，滴加式[C]-[Zn]所示锌试剂(1.2equiv)室温下搅拌3小时进行反应。以氟苯为内标试剂采用 19F NMR测定产物收率，NH 4Cl淬灭反应并采用EtOAc稀释干燥，水相采用乙酸乙酯洗涤(3×10mL),有机相采用Na 2SO 4干燥，过滤，收集。色谱纯化后产品直接 用于下一步制备反应。
25mL的史莱克瓶抽真空，并用Ar回填(3次)。然后加入环己烯(4mmol，8.0equiv)。冰浴中，在0℃下滴加BH3·THF(2mmol，4.0equiv)。搅拌5分钟后，将反应混合物加热至室温，搅拌1小时。加入上述粗产物。将所得混合物在室温下搅拌2小时。冷却至0℃滴加NaOH(7mmol，14.0equiv，2m)，然后加入H 2O 2(8mmol，16.0equiv，30％wt.)。搅拌15分钟后，将反应混合物加热至室温，搅拌2小时。所得混合物用加入饱和Na 2O 3，并用EtOAc稀释。水相用乙酸乙酯(3×10ml)萃取。合并的有机层用Na 2SO 4上干燥、过滤并浓缩。用硅胶色谱法纯化产物。
第一步：
Figure PCTCN2022115642-appb-000199
第二步：
Figure PCTCN2022115642-appb-000200
产品：
Figure PCTCN2022115642-appb-000201
黄色油状物，136mg,92％yield，三步，α/γ＝45：1由 19F NMR测定，硅胶层析纯化分离(石油醚/乙酸乙酯＝3:1) 1H NMR(400MHz,CDCl 3)δ3.87(t,J＝6.2Hz,2H),3.67(s,3H),2.30(t,J＝7.6Hz,2H),2.12(tt,J＝17.0,6.1Hz,2H),1.94–1.77(m,2H),1.64–1.57(m,2H),1.52–1.41(m,2H),1.36–1.23(m,12H). 19F NMR(376MHz,CDCl 3)δ-97.04(p,J＝17.0Hz,2F). 13C NMR(101MHz,CDCl 3)δ174.4,125.1(t,J＝240.3Hz),57.0(t,J＝5.5Hz),51.4,38.9(t,J＝24.5Hz),37.0(t,J＝24.8Hz),34.0,29.25,29.22,29.21,29.1,29.0,24.9,22.2(t,J＝4.7Hz).MS(FI):m/z(％)74(100),87,149,224,294([M] +).HRMS(FI)m/z:([M] +)Calculated for C 15H 28F 2O 3:294.2001；Found:294.2003.
产品：
Figure PCTCN2022115642-appb-000202
黄色油状物，68mg,66％yield，三步，α/γ＝48：1由 19F NMR测定，硅胶色谱纯化分离(石油醚/乙酸乙酯＝5:1) 1H NMR(400MHz,CDCl 3)δ3.87(t,J＝6.2Hz,2H),2.12(tt,J＝17.1,6.2Hz,2H),1.96–1.77(m,2H),1.53–1.41(m,2H),1.35–1.27(m,10H),0.88(t,J＝6.8Hz,3H). 19F NMR(376MHz,CDCl 3)δ-97.07(p,J＝17.0Hz). 13C NMR(126MHz,CDCl 3)δ125.2(dd,J＝241.4,239.3Hz),57.1(t,J＝5.4Hz),38.9(t,J＝24.4Hz),37.0(t,J＝24.8Hz),31.8,29.3,29.1,22.6,22.2(t,J＝4.5Hz),14.1.MS(FI):m/z(％)85(100),124,168,188([M-HF] +).HRMS(FI)m/z:([M] +)Calculated for C 11H 22F 2O:208.1633；Found:208.1637.
产品：
Figure PCTCN2022115642-appb-000203
黄色油状物，123mg,84％yield，三步，α/γ＝99：1由 19F NMR测定，硅胶色谱纯化分离(石油醚/乙酸乙酯＝5:1) 1H NMR(400MHz,CDCl 3)δ7.41(d,J＝8.4Hz,2H),7.05(d,J＝8.4Hz,2H),3.85(t,J＝6.0Hz,2H),2.62(t,J＝7.2Hz,2H),2.18–2.04(m,2H),1.97–1.74(m,4H),1.65(br,1H). 19F NMR(376MHz,CDCl 3)δ-97.30(p,J＝16.8Hz,2F). 13C NMR(126MHz,CDCl 3)δ140.3,131.4,130.1,124.78(t,J＝240.6Hz),119.7,56.8(t,J＝5.6Hz),38.9(t,J＝24.4Hz),36.2(t,J＝25.1Hz),34.6,23.6(t,J＝4.6Hz).MS(EI):m/z(％)90,182(100),203,292([M] +).HRMS(EI)m/z:([M] +)Calculated for C 12H 15F 2OBr:292.0269；Found:292.0272.
应用实施例5
0.1mol％的CuBr加入50mL的史莱克瓶中，加入式C所示的二氟烯丙基鎓盐(5mmol,1.0equiv)，抽真空充Ar三次。加入10.0mL的THF，滴加式[C]-[Zn]所示锌试剂(1.2equiv)室温下搅拌10小时进行反应。以氟苯为内标试剂采用 19F NMR测定产物收率，NH 4Cl淬灭反应并采用EtOAc稀释干燥，水相采用乙酸乙酯洗涤(3×10mL),有机相采用Na 2SO 4干燥，过滤，收集。所得中间体经由Pd/C还原双键得目标产物，还原条件如下：Pd/C(21.2mg,10％)和上述产物0.2mmol加入2mL DCM，室温通入H 2(1atm)24h。
Figure PCTCN2022115642-appb-000204
产品：
Figure PCTCN2022115642-appb-000205
黄色油状物，1.31g,88％yield，α/γ＝50：1由 19F NMR测定，FP ECOFLEX C18(20g)(MeCN:H 2O＝6:4)分离纯化， 1H NMR(400MHz,CDCl 3)δ8.09(d,J＝8.0Hz,2H),7.57(d,J＝8.0Hz,2H),6.14(dq,J＝17.4,10.6Hz,1H),5.57(dt,J＝17.4,2.9Hz,1H),5.51(d,J＝10.6Hz,1H),4.42(t,J＝6.2Hz,2H),2.87(t,J＝6.2Hz,2H),2.65(q,J＝7.2Hz,4H),1.08(t,J＝7.2Hz,6H). 19F NMR(376MHz,CDCl 3)δ-94.47(d,J＝9.6Hz,2F). 13C NMR(101MHz,CDCl 3)δ165.7,140.4(t,J＝27.4Hz),133.2(t,J＝29.3Hz),131.7,129.6,125.5(t,J＝5.6Hz),120.2(t,J＝9.2Hz),118.7(t,J＝239.1Hz),63.5,50.8,47.6,11.9.MS(DART):m/z(％)86(100),105,181,225,297([M] +).HRMS(DART)m/z:([M+H] +)Calculated for C 16H 21F 2O 2N:298.1613；Found:298.1610.
应用实施例6
2.5mol％的CuBr加入25mL的史莱克瓶中，加入式C所示的二氟烯丙基鎓盐(1mmol,1.0equiv)，抽真空充Ar三次。加入3.0mL的THF，滴加式[C]-Zn]所示锌试剂(1.2equiv)室温下搅拌3小时进行反应。NH 4Cl淬灭反应并采用EtOAc稀释，水相采用乙酸乙酯洗涤(3×10mL),有机相采用Na 2SO 4干燥，过滤，收集产物。如下式所示，所得二氟类化合物可在Grubbs第II代催化剂作用下和1-辛烯反应于DCM中反应，得到化合物8，化合物8可经过Pd/C还原反应和水解反应得到终产物化合物9。
Figure PCTCN2022115642-appb-000206
产品：
Figure PCTCN2022115642-appb-000207
微黄色油状物，211mg,90％yield，α/γ＝50：1由 19F NMR测定，FP ECOFLEX C18(20g)(MeCN:H 2O＝7:3)分离纯化 1H NMR(400MHz,CDCl 3)δ5.89(dq,J＝17.4,11.0Hz,1H),5.60(dt,J＝17.4,2.5Hz,1H),5.40(d,J＝11.0Hz,1H),4.12(q,J＝7.2Hz,2H),2.29(t,J＝7.6Hz,2H),1.95–1.82(m,2H),1.68–1.58(m,2H),1.50–1.41(m,2H),1.41–1.27(m,4H),1.25(t,J＝7.2Hz,3H). 19F NMR(376MHz,CDCl 3)δ-97.73–-98.06(m,2F). 13C NMR(101MHz,CDCl 3)δ173.7,133.1(t,J＝27.7Hz),121.3(t,J＝238.4Hz),118.9(t,J＝9.5Hz),60.1,37.0(t,J＝26.4Hz),34.2,28.9,28.8,24.7,22.1(t,J＝4.3Hz),14.2.MS(EI):m/z(％)88(100),126,234([M] +).HRMS(EI)m/z:([M] +)Calculated for C 12H 20F 2O 2:234.1426；Found:234.1430.
在本发明提及的所有文献都在本申请中引用作为参考，就如同每一篇文献被单独引用作为参考那样。此外应理解，在阅读了本发明的上述讲授内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。

Claims (15)

  1. 一种如式C所示的3，3-二氟烯丙基鎓盐，
    Figure PCTCN2022115642-appb-100001
    其中，Z＝S，Se或Te；X为阴离子；
    R 1、R 2、R 3和R 4独立地为H、F、Cl、Br、I、C 1-C 20的烷基、被一个或多个R 5取代的C 1-C 20的烷基、C 1-C 20的杂烷基、被一个或多个R 6取代的C 1-C 20的杂烷基、C 6-C 20的芳基、被一个或多个R 7取代的C 6-C 20的芳基、5-20元的杂芳基或被一个或多个R 8取代的5-20元的杂芳基；其中，所述的C 1-C 20的杂烷基的杂原子或杂原子团选自C(＝O)、S(＝O)、S(＝O) 2、SO 2NR 1’R 2’、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；所述的5-20元的杂芳基的杂原子选自S、O、N、Si、P和B，杂原子个数为1个或多个；
    或者，R 1和R 4与相连的Z一起形成：5-20元的杂环烷基、被一个或多个R 9取代的5-20元的杂环烷基、5-20元的杂芳基或被一个或多个R 10取代的5-20元的杂芳基；所述的5-20元的杂环烷基的杂原子或杂原子团选自C(＝O)、S、S(＝O)、S(＝O) 2、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；所述的5-20元的杂芳基的杂原子或杂原子团选自C(＝O)、S、S(＝O)、S(＝O) 2、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；
    每个R 5、R 6、R 7、R 8、R 9和R 10独立地为F、Cl、Br、I、C 1-C 20的烷基、C 3-C 20的环烷基、C 6-C 20的芳基、C 2-C 20的炔基、C 2-C 20的烯基、C 1-C 20的杂烷基、被一个或多个R 1a取代的C 1-C 20的烷基、被一个或多个R 1b取代的C 3-C 20的环烷基、被一个或多个R 1c取代的C 6-C 20的芳基、一个或多个R 1d取代的C 2-C 20的炔基、被一个或多个R 1e取代的C 1-C 20的杂烷基、被一个或多个R 1f取代的C 2-C 20的烯基；所述的C 1-C 20的杂烷基的杂原子或杂原子团选自C(＝O)、S(＝O)、S(＝O) 2、SO 2NR 1’R 2’、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；
    每个R 1’、R 2’、R 3’和R 4’独立地为C 1-C 20的烷基、C 3-C 20的环烷基、C 6-C 20的芳基、被一个或多个R 1a取代的C 1-C 20的烷基、被一个或多个R 1b取代的C 3-C 20的环烷基、被一个或多个R 1c取代的C 6-C 20的芳基；
    每个R 1a、R 1b、R 1c、R 1d、R 1e和R 1f独立地为F、Cl、Br、I、N 3、C 1-C 20的烷基、C 6-C 20的芳基或独立地被三个C 1-C 4烷基取代的硅烷基。
  2. 如权利要求1所述的如式C所示的3，3-二氟烯丙基鎓盐，其特征在于，所述R 5、R 6、R 7、R 8、R 9和R 10独立地为F、Cl、Br、I、C 1-C 20的烷基、C 3-C 20的环烷基、C 6-C 20的芳基、C 2-C 20的炔基、C 1-C 20的杂烷基、被一个或多个R 1a取代的C 1-C 20的烷基、被一个或多个R 1b取代的C 3-C 20的环烷基、被 一个或多个R 1c取代的C 6-C 20的芳基、一个或多个R 1d取代的C 2-C 20的炔基、被一个或多个R 1e取代的C 1-C 20的杂烷基；所述的C 1-C 20的杂烷基的杂原子或杂原子团选自C(＝O)、S(＝O)、S(＝O) 2、SO 2NR 1’R 2’、O、N、Si、P、P(＝O)、PO(OR 3’) 2、PS(OR 3’) 2、B(R 4’) 2和B(OR 4’) 2，杂原子和杂原子团的个数为1个或多个；
    所述R 1a、R 1b、R 1c、R 1d和R 1e独立地为F、Cl、Br、I、N 3、C 1-C 20的烷基。
  3. 如权利要求1所述的如式C所示的3，3-二氟烯丙基鎓盐，其特征在于，所述如式C所示的3，3-二氟烯丙基鎓盐满足下述条件中的一个或多个：
    (1)X为有机或者无机阴离子，例如为三氟甲磺酸阴离子、氟硼酸阴离子、六氟磷酸阴离子、六氟锑酸阴离子、对甲苯磺酸阴离子、氟阴离子、氯阴离子、溴阴离子、碘阴离子；
    (2)所述的C 1-C 20的烷基、被取代的C 1-C 20的烷基里的C 1-C 20的烷基独立地为C 1-C 10的烷基，又如C 1-C 6的烷基，还如甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基；
    (3)所述的C 1-C 20的杂烷基、被取代的C 1-C 20的杂烷基里的C 1-C 20的杂烷基独立地为-C(＝O)O-杂化的C 1-C 20的烷基；例如-C(＝O)OMe；
    (4)所述的C 6-C 20的芳基、被取代的C 6-C 20的芳基里的C 6-C 20的芳基独立地为苯基；
    (5)所述的R 1和R 4与相连的Z一起形成：5-20元的杂环烷基、被取代的5-20元的杂环烷基里的5-20元的杂环烷基独立地为5-10元的杂环烷基，例如
    Figure PCTCN2022115642-appb-100002
    (6)所述的R 1和R 4与相连的Z一起形成：5-20元的杂芳基、被取代的5-20元的杂芳基里的5-20元的杂芳基独立地为5-10元的杂芳基，例如苯并噻吩
    Figure PCTCN2022115642-appb-100003
    (7)所述的C 3-C 20的环烷基独立地为环丙基、环丁基、环戊基或环己基；
    (8)所述的C 2-C 20的炔基、被取代的C 2-C 20的炔基里的C 2-C 20的炔基独立地为C 2-C 10的炔基，又如C 2-C 6的炔基，还如
    Figure PCTCN2022115642-appb-100004
  4. 如权利要求1所述的如式C所示的3，3-二氟烯丙基鎓盐，其特征在于，所述如式C所示的3，3-二氟烯丙基鎓盐满足下述条件中的一个或多个：
    (1)所述的C 1-C 20的烷基、被取代的C 1-C 20的烷基里的C 1-C 20的烷基独立地为正己基；
    (2)所述的C 1-C 20的杂烷基、被取代的C 1-C 20的杂烷基里的C 1-C 20的杂烷基独立地为-C(＝O)O-或-O-杂化的C 1-C 20的烷基，例如-C(＝O)OEt、-OCH 3；
    (3)所述的C 2-C 20的烯基、被取代的C 2-C 20的烯基里的C 2-C 20的烯基独立地为C 2-C 10的烯基， 又如C 2-C 6的烯基，还如
    Figure PCTCN2022115642-appb-100005
    (4)所述R 4独立地为C 1-C 20的烷基，优选C 1-C 6的烷基，例如甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基；
    (5)X为有机或者无机阴离子，例如为四苯硼酸阴离子。
  5. 如权利要求3或4所述的如式C所示的3，3-二氟烯丙基鎓盐，其特征在于，所述如式C所示的3，3-二氟烯丙基鎓盐满足下述条件中的一个或多个：
    (1)R 1、R 2、R 3和R 4独立地为H、F、Cl、Br、Me、Et、苯基、甲苯基、甲氧基苯基、溴代苯基、三(甲基)苯基、三(异丙基)苯基、苯基亚乙基、-C(＝O)OMe、
    Figure PCTCN2022115642-appb-100006
    Figure PCTCN2022115642-appb-100007
    (2)所述的R 1和R 4与相连的Z一起形成：
    Figure PCTCN2022115642-appb-100008
    Figure PCTCN2022115642-appb-100009
    Alkyl独立地为所述的C 1-C 20的烷基、被一个或多个R 5取代的C 1-C 20的烷基；例如
    Figure PCTCN2022115642-appb-100010
  6. 如权利要求3或4所述的如式C所示的3，3-二氟烯丙基鎓盐，其特征在于，所述如式C所示的3，3-二氟烯丙基鎓盐满足下述条件中的一个或多个：
    (1)所述R 1、R 2、R 3和R 4独立地为叔丁基苯基、正己基、
    Figure PCTCN2022115642-appb-100011
    (2)所述R 4独立地为Me或Et；
    (3)所述R 1和R 4中一个为Me或Et，另一个为苯基、甲苯基、甲氧基苯基、溴代苯基、三(甲基)苯基、三(异丙基)苯基或苯基亚乙基。
  7. 如权利要求1所述的如式C所示的3，3-二氟烯丙基鎓盐，其特征在于，所述如式C所示的3，3-二氟烯丙基鎓盐为如下任一结构：
    Figure PCTCN2022115642-appb-100012
    Figure PCTCN2022115642-appb-100013
    其中，X的定义如上所述；X为F、Cl、Br、BF 4、OTf、BPh 4、PF 6、TeF 6或SbF 6，TIPP为三(异丙基)苯基，Mes为2,4,6-三甲苯基，Tol为甲苯基，Alkyl独立地为所述的C 1-C 20的烷基、被一个或多个R 5取代的C 1-C 20的烷基；Ar独立地为所述的C 6-C 20的芳基、被一个或多个R 7取代的C 6-C 20的芳基。
  8. 如权利要求1所述的如式C所示的3，3-二氟烯丙基鎓盐，其特征在于，所述如式C所示的3，3-二氟烯丙基鎓盐为如下任一化合物：
    Figure PCTCN2022115642-appb-100014
    Figure PCTCN2022115642-appb-100015
  9. 一种如权利要求1至8中至少一项所述的如式C所示的3，3-二氟烯丙基鎓盐的制备方法，其特征在于，其包含如下步骤：
    在有机溶剂中，将如式D所示的化合物与烷基化试剂进行烷基化反应，得到如式C所示的3，3-二氟烯丙基鎓盐类化合物，即可；所述烷基化试剂为R 4X和/或R 4I与AgX的体系或R 4 3OBF 4；
    Figure PCTCN2022115642-appb-100016
    其中，Z、X、R 1、R 2、R 3和R 4的定义如权利要求1至8至少一项所示。
  10. 如权利要求9所述的如式C所示的3，3-二氟烯丙基鎓盐的制备方法，其特征在于，满足下述条件中的一个或多个：
    (1)所述的有机溶剂为非质子溶剂，如DCM、THF，DMF，DMSO；
    (2)所述的如式D所示的化合物与烷基化试剂的摩尔比为1:0.9至1:1.5，例如1:1、1.15:1；
    (3)所述的烷基化反应在氩气或氮气下进行；
    (4)所述的烷基化反应在0℃至140℃下进行，例如10至30℃。
  11. 如权利要求9所述的如式C所示的3，3-二氟烯丙基鎓盐的制备方法，其特征在于，其还包括所述如式D所示的化合物的制备方法，其包括如下步骤：
    在有机溶剂中，将如式A所示化合物和如式B所示的化合物进行如下式所示的取代反应，得到所述的如式D所示的化合物，即可；
    Figure PCTCN2022115642-appb-100017
    其中，Z、R 1、R 2和R 3的定义如权利要求9所示；
    X 1为F、Cl或Br；M 1为碱金属。
  12. 如权利要求11所述的如式C所示的3，3-二氟烯丙基鎓盐的制备方法，其特征在于，其满足下述条件中的一个或多个：
    (1)M 1为Na、K或Li；
    (2)所述的有机溶剂为非质子溶剂，如二氧六环、THF，DMF和DMSO中的一种或多种；
    (3)所述的如式A所示的化合物与如式B所示的化合物的摩尔比为1:1至1:3，例如1:1.2、1:1.25、1:2；
    (4)所述的取代反应在氩气或氮气下进行；
    (5)所述的取代反应在室温至140℃下进行，优选为50℃至140℃下进行，例如100±10℃。
  13. 一种如权利要求1至8中至少一项所述式C所示的3，3-二氟烯丙基鎓盐类化合物作为α,α-偕二氟烯丙基化试剂的应用。
  14. 如权利要求13所述式C所示的3，3-二氟烯丙基鎓盐类化合物作为α,α-偕二氟烯丙基化试剂的应用，其特征在于，所述的应用包括如下步骤：
    在溶剂中，将如式C所示的3，3-二氟烯丙基鎓盐类化合物与锌试剂进行如下所示的偶联反应，得到如式E所示的α,α-偕二氟烯丙基类化合物，即可；
    Figure PCTCN2022115642-appb-100018
    其中，Z、X、R 1、R 2、R 3和R 4的定义如权利要求1至8中至少一项所示；
    [C]表示通过Csp1、Csp2或Csp3与[Zn]连接的部分；[Zn]表示ZnX 2、Zn·LiX 2、ZnX 2·LiX 2；X 2独立地为溴或氯；
    例如[Zn]为ZnBr、ZnCl、Zn·LiCl、ZnCl·LiCl、ZnBr·LiCl。
  15. 如权利要求13或14所述式C所示的3，3-二氟烯丙基鎓盐类化合物作为α,α-偕二氟烯丙基化试剂的应用，其特征在于，其满足下述条件中的一个或多个：
    (1)所述的式C所示的3，3-二氟烯丙基鎓盐类化合物与锌试剂的摩尔比为1:1至1.5；例如1:1.1、1:1.2、1:1.3；
    (2)所述的偶联反应在催化剂存在下进行，所述的催化剂为CuBr；所述的催化剂的与所述的式C所示的3，3-二氟烯丙基鎓盐类化合物的摩尔比为0.2至0.005；例如0.01、0.025、0.05、0.1；
    (3)所述的偶联反应的温度为-78至35℃，例如室温下进行反应；
    (4)所述的溶剂为醚类溶剂；所述的醚类溶剂为四氢呋喃；
    (5)所述的锌试剂与相应的如式E所示的α,α-偕二氟烯丙基类化合物为如下的任一组：
    Figure PCTCN2022115642-appb-100019
    Figure PCTCN2022115642-appb-100020
    Figure PCTCN2022115642-appb-100021
    Figure PCTCN2022115642-appb-100022
    Figure PCTCN2022115642-appb-100023
    Figure PCTCN2022115642-appb-100024
    Figure PCTCN2022115642-appb-100025
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3426046A (en) * 1965-10-22 1969-02-04 Dow Chemical Co Synthesis of epoxides from allylic sulfonium salts
CN106349134A (zh) * 2016-07-27 2017-01-25 武汉理工大学 无溶剂制备含氟锍盐的方法
CN115260069A (zh) * 2021-09-01 2022-11-01 中国科学院上海有机化学研究所 一种3，3-二氟烯丙基鎓盐类化合物及其制备方法与应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107235878B (zh) * 2016-03-28 2019-03-15 中国科学院上海有机化学研究所 二氟甲基化试剂、其制备方法与应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3426046A (en) * 1965-10-22 1969-02-04 Dow Chemical Co Synthesis of epoxides from allylic sulfonium salts
CN106349134A (zh) * 2016-07-27 2017-01-25 武汉理工大学 无溶剂制备含氟锍盐的方法
CN115260069A (zh) * 2021-09-01 2022-11-01 中国科学院上海有机化学研究所 一种3，3-二氟烯丙基鎓盐类化合物及其制备方法与应用

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
GU, WENXIANG: "Synthesis of a new sulfonium salt", HUAXUE SHIJI - CHEMICAL REAGENTS, BEIJING : HUAXUE HUAXUE SHIJI KEJI QINGBAO ZHONGXINZHAN, CN, vol. 14, no. 6, 31 December 1992 (1992-12-31), CN , pages 364, 376, XP009544255, ISSN: 0258-3283, DOI: 10.13822/j.cnki.hxsj.1992.06.016 *
LEO A. PAQUETTE: "Encyclopedia of reagents for organic synthesis; Vol. 7 : Sod - Trim", WILEY , Chichester , ISBN: 978-0-470-84289-8, article CHAMBLEE THERESA S.: "3-Bromo-1,1-dichloro-1-propene", XP093043196, DOI: 10.1002/047084289X.rb287m *
MIN QIAO-QIAO, YIN ZENGSHENG, FENG ZHANG, GUO WEN-HAO, ZHANG XINGANG: "Highly Selective gem -Difluoroallylation of Organoborons with Bromodifluoromethylated Alkenes Catalyzed by Palladium", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 136, no. 4, 29 January 2014 (2014-01-29), pages 1230 - 1233, XP093043181, ISSN: 0002-7863, DOI: 10.1021/ja4114825 *
OSUKA OSUKA ATSUHIRO ATSUHIRO, SUZUKI HITOMI: "Dialkyltelluronium allylide as a novel reagent for synthesis of α,β-unsaturated epoxides", TETRAHEDRON LETTERS, ELSEVIER, AMSTERDAM , NL, vol. 24, no. 46, 1 January 1983 (1983-01-01), Amsterdam , NL , pages 5109 - 5112, XP093043198, ISSN: 0040-4039, DOI: 10.1016/S0040-4039(00)94054-1 *
XUN HAN, YE, SUN LONGWU B, XIULI: "Cyclization Reactions for the Stereoselective Synthesis of Small Ring Compounds via Selenonium and Telluronium Ylides", CHINESE JOURNAL OF ORGANIC CHEMISTRY, vol. 29, no. 3, 1 January 2009 (2009-01-01), pages 306 - 320, XP093043201 *
YE FEI, GE YAO, SPANNENBERG ANKE, NEUMANN HELFRIED, XU LI-WEN, BELLER MATTHIAS: "3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents", NATURE COMMUNICATIONS, vol. 12, no. 1, XP093043184, DOI: 10.1038/s41467-021-23504-2 *
ZHANG, XIAOMEI: "Synthesis and Reactions of Dimethyl-3,3-dichloro-2-propenylsulfonium Chloride", ACTA CHIMICA SINICA, vol. 48, no. 3, 1 January 1990 (1990-01-01), pages 273 - 282, XP093043193 *

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