A perfluoro-tert-butylation reagent and a method for preparing the same

Abstract

The application provides a perfluoro-tert-butylating agent and a preparation method thereof, and the perfluoro-tert-butylating agent has a structure as shown in formula 1. The agent can realize controllable perfluoro-tert-butylating reaction of an organic substrate, so that a series of novel perfluoro-tert-butylated compounds can be prepared in a mild and efficient manner.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to a perfluoro-tert-butylating reagent and a preparation method thereof. BACKGROUND

[0002] Due to the wide application of fluorine-containing alkyl compounds in drug development, organic functional material design and the like, fluoralkylation reactions have been widely concerned in the past two or three decades. In order to introduce fluoralkyl into an organic molecule, a series of fluoralkylating reagents (such as Togni reagent, Umemoto reagent, Chen reagent and the like) have been developed, and according to the reactivity of fluoralkyl, these reagents can be further classified into electrophilic, nucleophilic and radical types.

[0003] The most widely studied perfluoroalkylation reaction at present is undoubtedly trifluoromethylation. This is because trifluoromethyl compounds play an important role in changing the liposolubility and electrostatic potential of molecules (fluorine effect), and on the other hand, trifluoromethyl is the smallest and most basic structural unit of perfluoroalkyl, and the study of its properties is of the most universal significance. In recent years, many groups have been reported to act as "super trifluoromethyl" (such as perfluoroisopropyl, perfluoro-tert-butyl), which can significantly change the properties of molecules, such as greatly improving the physiological activity or metabolic stability of drug molecules. Compared with other "super trifluoromethyl", perfluoro-tert-butylating reaction has its special attraction. This is because its nine chemically equivalent fluorine atoms bring unique 19 F-NMR properties, which makes perfluoro-tert-butyl compounds have great application value in sensing and imaging.

[0004] However, due to the strong steric effect and electronic effect of perfluoro-tert-butyl itself, the perfluoro-tert-butylation reaction of organic molecules faces great difficulties, and the current mature method for introducing perfluoro-tert-butyl fragments is based on the photo-Claisen reaction of perfluoro-tert-butyl alcohol (i.e. perfluoro-tert-butyloxylation).

[0005] Nucleophilic perfluoro-tert-butylation reagents based on perfluoro-tert-butylic anion were reported in the last century, but the common fluorine-containing small molecules used to prepare perfluoro-tert-butylic anion are mostly highly toxic and unstable. Due to the lack of stable, safe and available reagents, perfluoro-tert-butylation reaction has not made substantial progress until recently: in 2021, the first method for preparing perfluoro-tert-butylic cesium from a stable, safe precursor was reported, and this unstable species was used in nucleophilic substitution reactions with "alkyl-leaving groups", activated perfluoroarenes to prepare a series of sp 2 / sp 3C-Perfluoro-t-Butyl Compounds (Angew. Chem. Int. Ed., 2021, 60, 27318-27323.); In 2022, the perfluoro-t-butyl sulfone compound was formed by using hypofluorous acid to oxidize perfluoro-t-butyl sulfide in the literature, and the regioselective nucleophilic perfluoro-t-butyl reaction of phenylacetylene was realized by perfluoro-t-butyl sulfone (J. Am. Chem. Soc., 2022, 144, 48, 22281-22288.).

[0006] The electrophilic / free radical type reaction has not been widely studied at present, which is mainly because of the lack of corresponding perfluoro-t-butylating reagents. Previously, perfluoro-t-butyl halide has been proved to be able to provide perfluoro-t-butyl radicals, but perfluoro-t-butyl halide is mostly a compound with low boiling point and high toxicity, and the synthesis steps are complex, so it lacks practical value.

[0007] In summary, the perfluoro-t-butyl reaction of the organic molecule at present is concentrated on the nucleophilic reaction between the perfluoro-t-butyl anion and the highly active reaction substrate.

[0008] In recent years, the carbon-oxygen bond cleavage of alcohol has gradually become an important way to realize the alkylation reaction. As the only commercially available perfluoro-t-butyl compound, perfluoro-t-butanol has extremely weak nucleophilic ability and is often used as an organic solvent. The corresponding anion is often used as the counter anion of imidazole type ionic liquid. The strong electronic and steric effects make it extremely difficult to activate the carbon-oxygen bond of perfluoro-t-butanol, so it is extremely valuable and challenging to use perfluoro-t-butanol as a perfluoro-t-butyl source to develop a perfluoro-t-butylating reagent. SUMMARY

[0009] The purpose of the present application is to solve the limitations of the current perfluoro-t-butyl reaction and develop a new type of perfluoro-t-butylating reagent: perfluoro-t-butoxy-substituted azaheterocyclic onium salt. By using the unique reactivity of the reagent, the perfluoro-t-butyl reaction of small organic molecules such as olefins, alkynes and aromatic rings can be realized. In particular, the reagent used in the present application is cheap and easy to obtain, can be prepared in large quantities and can be stored for a long time, and is an obtainable perfluoro-t-butylating reagent. According to the embodiments of the present application, a strong electrophilic reagent based on the azaheterocyclic skeleton is provided, which is reacted with perfluoro-t-butanol to further selectively activate the carbon-oxygen bond. According to the embodiments of the present application, a highly active azaheterocyclic hypervalent iodine (III) reagent is designed and synthesized from PIFA (bis-trifluoroacetoxyiodobenzene, commercially available), which selectively realizes the carbon-oxygen coupling with the perfluoro-t-butanol anion, and develops an obtainable perfluoro-t-butylating reagent based thereon. By using this reagent, the present application realizes the perfluoro-t-butyl reaction of olefins, alkynes and aromatic ring substrates, and controllably obtains a series of novel perfluoro-t-butyl compounds.

[0010] In a first aspect, the present application provides a perfluoro-t-butylation reagent. According to embodiments of the present application, the perfluoro-t-butylation reagent has a structure as shown in Formula 1,

[0011]

[0012] the dashed line in Formula 1 represents the presence or absence of a phenyl group;

[0013] R 1 is alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl;

[0014] Y is O, S, S=O, S(=O)2, NR Y ;

[0015] R Y is alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl;

[0016] X is triflate, tetrafluoroborate, hexafluorophosphate, or trifluoroacetate;

[0017] R 2 is H, halogen, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl.

[0018] According to embodiments of the present application, R 1 is alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl, and the remaining variables are as defined in the present application.

[0019] According to embodiments of the present application, R 2 is H, halogen, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl.

[0020] According to embodiments of the present application, the perfluoro-t-butylation reagent has a structure as shown in Formula 1, and the remaining variables are as defined in the present application.

[0021] In another aspect, the present application also provides a method for preparing a compound shown in Formula (1). According to embodiments of the present application, the method comprises:

[0022] substituting a compound shown in Formula (3) with R 1 X to obtain a compound shown in Formula (1),

[0023]

[0024] wherein R 1 is alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl;

[0025] Y is O, S, S=O, S(=O)2, NR Y ;

[0026] R Y is H, halogen, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl.

[0027] X is triflate, tetrafluoroborate, hexafluorophosphate, or trifluoroacetate;

[0028] R 2 is H, halogen, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl.

[0029] According to an embodiment of the present application, the compound of formula (3) is obtained by reacting a compound of formula (2) with perfluoro-tert-butyl alcohol,

[0030] the remaining variables are as defined in the present application.

[0031] According to an embodiment of the present application, the compound of formula (2) is obtained by reacting a compound of formula (4) with bis(trifluoroacetoxy)iodobenzene,

[0032] the remaining variables are as defined in the present application.

[0033] According to an embodiment of the present application, the compound of formula (1) has the structure the remaining variables are as defined in the present application.

[0034] According to an embodiment of the present application, the compound of formula (3) has the structure the remaining variables are as defined in the present application.

[0035] According to an embodiment of the present application, the compound of formula (2) has the structure the remaining variables are as defined in the present application.

[0036] According to an embodiment of the present application, the compound of formula (1) has the structure the remaining variables are as defined in the present application.

[0037] In yet another aspect of the present application, a method for preparing the perfluoro-tert-butylation reagent described above is also provided. According to an embodiment of the present application, the method employs a synthetic scheme as shown in the figure:

[0038]

[0039] The specific synthesis steps are as follows:

[0040]

[0041] The first step, PIFA (bis-trifluoroacetoxyiodobenzene) is dissolved in dichloromethane at room temperature. Arylsilane is added dropwise into the above suspension under magnetic stirring at room temperature. The suspension gradually becomes a homogeneous solution, which is stirred at room temperature for 1 hour. At this time, white solid is precipitated in the solution, and the system is added with low-polarity solvent in an equal volume to the solvent under magnetic stirring, and the precipitated solid in the solution is increased. The mixture is cooled to -20 degrees Celsius, and the solid is further precipitated. Filtration is performed, and the filter cake is washed with low-polarity solvent until white, to obtain (aryl)(phenyl)-λ 3 -iodo trifluoroacetate 2;

[0042]

[0043] The second step, perfluoro-t-butyl alcohol is dissolved in tetrahydrofuran to prepare a solution under magnetic stirring and nitrogen protection at room temperature, and then the solution is cooled to 0 degrees Celsius, and n-butyllithium hexane solution is slowly added dropwise. The reaction is continued at 0 degrees Celsius for 10 minutes, and then (aryl)(phenyl)-λ 3 -iodo trifluoroacetate 2 is added to the solution, the cooling device is removed, the mixture is heated to 60 degrees Celsius, and the reaction is continued for several hours. After returning to room temperature, the solvent is removed by rotary evaporation, and then fast column chromatography is performed to obtain perfluoro-t-butoxy compound 3;

[0044]

[0045] The third step, perfluoro-t-butoxy compound 3 is dissolved in dichloromethane, and then an electrophilic reagent R 1 X is added, heated to reflux, cooled to room temperature, and then low-polarity solvent is added to the mixture, cooled to -20 degrees Celsius, and filtered. The obtained solid is washed with a small amount of low-polarity solvent, to obtain compound 1.

[0046] According to the embodiment of the present application, the concentration of the reaction solution in the first step should be 0.3-2.0 mol / L, and the low-polarity solvent is one or more of ethyl ether, hexane, and pentane, and the remaining variables are as defined in the present application.

[0047] According to the embodiment of the present application, the ratio of PIFA to arylsilane in the first step is 2 / 1-1 / 2, and the remaining variables are as defined in the present application.

[0048] According to the embodiment of the present application, the concentration of perfluoro-t-butyl alcohol dissolved in tetrahydrofuran to prepare a solution in the second step is 0.5-2.0 mol / L, and the remaining variables are as defined in the present application.

[0049] According to the embodiment of the present application, the concentration of perfluoro-t-butoxy compound 3 in dichloromethane in the third step is 0.5-2.0 mol / L, and the remaining variables are as defined in the present application.

[0050] According to an embodiment of the present application, the low polarity solvent in the third step is one or more of diethyl ether, hexane, pentane, and the rest of the variables are as defined in the present application.

[0051] According to an embodiment of the present application, the present application has at least one of the following beneficial effects:

[0052] The perfluoro-tert-butylation reagent provided herein is cheap and easy to obtain, can be prepared in large quantities and can be stored for a long time, and is an example of an easily accessible perfluoro-tert-butylation reagent. Under appropriate conditions, the perfluoro-tert-butylation reaction of relatively inert substrates can be achieved mildly, and novel perfluoro-tert-butylation compounds with high added value can be prepared.

[0053] In the process of preparing the reagent, the present application develops a new class of highly active heteroaryl hypervalent iodine (III) reagent from PIFA, which can highly selectively transfer heteroaryl groups without transferring benzene rings. However, previous literature on perfluoro-tert-butyloxylation based on hypervalent iodine strategy needs to rely on specific "non-transferring groups" (Org. Lett., 2019, 21, 13, 5206-5210.).

[0054] Definitions and explanations of terms

[0055] Unless otherwise specified, the groups and terms defined in the specification and claims of the present application, including their definitions as examples, exemplary definitions, preferred definitions, definitions in tables, definitions of specific compounds in examples, etc., can be combined and combined with each other. The group definition and compound structure after such combination should be understood as within the scope recorded in the specification and / or claims of the present application.

[0056] In this text, the term "optional" means that both the presence and absence of the feature, which means that the event described later can but does not necessarily occur, so as to include both cases of the occurrence or non-occurrence of the event. For example, "heterocyclic group optionally substituted with alkyl" means that the alkyl group can but does not necessarily exist, so as to include the case of heterocyclic group substituted with alkyl and the case of heterocyclic group without being substituted with alkyl.

[0057] As described herein, the compounds of the application can contain "optionally substituted" moieties. In general, the term "substituted", whether preceded by the term "optionally" or not, means that the indicated moiety can be substituted with suitable substituents, as described below. Unless otherwise indicated, "optionally substituted" groups can have suitable substituents at each substitutable position of the group, and when more than one position in any given structure can be substituted with a substituent selected from a specified group, the substituent can be the same or different at every position. Combinations of substituents envisioned by this application are preferably those that result in the formation of stable or chemically feasible compounds. The term "stable", as used herein, refers to compounds that are not substantially altered when subjected to conditions in which the compounds typically are used or stored.

[0058] Each optional substituent on a substitutable carbon is independently selected from the group consisting of monovalent substituents =0; cyano; C 1-6 alkyl; C 2-6 alkenyl; C 2-6 alkynyl; haloC 1-6 alkyl, C 1-6 alkoxy; halo; -(CH2) 0-4 Ro; -(CH2) 0-4 ORo; -O(CH2) 0- 4Ro; -O-(CH2) 0-4 C(O)ORo; -(CH2) 0-4 CH(ORo)2; -(CH2) 0-4 SRo; -(CH2) 0-4 Ph, which can be substituted with Ro; -(CH2) 0-4 O(CH2) 0-1 Ph, which can be substituted with Ro; -CH=CHPh, which can be substituted with Ro; -(CH2) 0-4 O(CH2)0-1-pyridyl, which can be substituted with Ro; -NO2; -CN; -N3; -(CH2) 0-4 N(Ro)2; -(CH2) 0-4 N(Ro)C(O)Ro; -N(Ro)C(S)Ro; -(CH2) 0-4 N(Ro)C(O)NRo2; -N(Ro)C(S)NRo2; -(CH2) 0-4 N(Ro)C(O)-ORo; -N(Ro)N(Ro)C(O)Ro; -N(Ro)N(Ro)C(O)NRo-2; -N(Ro)N(Ro)C(O)ORo; -(CH2) 0-4 C(O)Ro; -C(S)-Ro; -(CH-2) 0-4C(O)ORo; -(CH2) 0-4 C(O)SRo; -(CH2) 0-4 C(O)OSiRo3; -(CH2) 0-4 OC(O)Ro; -OC(O)-(CH-2) 0-4 SR-; SC(S)SRo; -(CH2) 0-4 SC(O)Ro; -(CH2) 0-4 C(O)NRo2; -C(S)NRo2; -C(S)SRo; -SC(S)-SRo; -(CH2) 0- 4OC(O)NRo2; -C(O)N(ORo)Ro; -C(O)C(O)Ro; -C(O)CH2C(O)Ro; -C(NORo)Ro; --(CH2) 0-4 SSRo; -(CH2) 0-4 S(O)2Ro; -(CH2) 0-4 S(O)2ORo; -(CH2) 0-4 OS(O)2Ro; -S(O)2NRo2; -S(O)-(NRo)Ro; -S(O)2NC(NRo2)2; -(CH2) 0-4 S(O)Ro; -N(Ro)S(O)2NRo2; -N(Ro)S(O)2Ro; -N(ORo)Ro; -C(NH)NRo2; -P(O)2Ro; -P(O)Ro2; -OP(O)Ro2; -OP(O)(ORo)2; SiRo3; -(C 1-4 straight or branched chain alkylene)O-N(Ro)2; or -(C 1-4 straight or branched chain alkylene)C(O)O-N(Ro)2.

[0059] each Ro is independently hydrogen, C 1-6 aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, -CH2-(5-6 membered heteroaryl ring), or a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two occurrences of Ro, taken together with their intervening atom(s), form a 3-12 membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which can be substituted at a saturated carbon atom of Ro with a divalent substituent selected from =O and =S; or each Ro is optionally substituted with a monovalent substituent independently selected from halogen, -(CH2) 0-2 R, -(haloR), -(CH2) 0-2 OH, -(CH2) 0-2 OR, -(CH2)0-2 CH(OR)2, -O(haloR), -CN, -N3, -(CH2) 0-2 C(O)R, -(CH2) 0-2 C(O)OH, -(CH2) 0-2 C(O)OR, -(CH2) 0-2 SR., -(CH2) 0-2 SH, -(CH2) 0- 2NH2, -(CH2) 0-2 NHR, -(CH2) 0-2 NR2, -NO2, -SiR3, -OSiR3, -C(O)SR, -(C1-4straight or branched alkylene)C(O)OR, or -SSR.

[0060] each R* is independently selected from C 1-4 aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or a 5-6 membered saturated, partially unsaturated, or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein each R is unsubstituted or, when preceded by halo, substituted only with one or more halogens; or wherein the optional substituent on a saturated carbon is a divalent substituent independently selected from =0, =S, =NNR*2, =NNHC(O)R*, =NNHC(O)OR*, =NNHS(O)2R*, =NR*, =NOR*, -O(C(R*2) 2-3 O-, or -S(C(R*2) 2-3 S-, or the divalent substituent bound to an adjacent substitutable carbon of a "optionally substituted" group is -O(CR*2) 2-3 O-, wherein each individual occurrence of R* is selected from hydrogen, C1-6aliphatic, or an unsubstituted 5-6 membered saturated, partially unsaturated, or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0061] when R* is C1-6aliphatic, R* is optionally substituted with halogen, -R, -(haloR), -OH, -OR, -O(haloR), -CN, -C(O)OH, -C(O)OR, -NH2, -NHR, -NR2, or -NO2, wherein each R is independently selected from C1-4aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or a 5-6 membered saturated, partially unsaturated, or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein each R is unsubstituted or, when preceded by halo, substituted only with one or more halogens.

[0062] the optional substituent on a substitutable nitrogen is independently:

[0063]

[0064] wherein each independently is hydrogen, a Ci_6aliphatic, unsubstituted -OPh, or an unsubstituted 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of together with their intervening atoms form an unsubstituted 3-12 membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein when is a Ci_6aliphatic, optionally substituted with halogen, -R·, -(haloR·), -OH, -OR·, -O(haloR·), -CN, -C(O)OH, -C(O)OR·, -NH2, -NHR·, -NR·2, or -NO2, wherein each R·is independently selected from a Ci_4aliphatic, -CH2Ph, -O(CH2)0-1Ph, or a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein each R·is unsubstituted or, if halo- substituted, substituted with one or more halogen.

[0065] Unless otherwise indicated, the numerical values in this disclosure and the claims recite a range of values equivalent to at least the recited individual end point values. For example, a numerical range of "1-12" recites a range of values equivalent to each individual integer value within the range of 1-12, i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.

[0066] The term "C 1-20 alkyl" is understood to mean straight and branched chain alkyl groups having from 1 to 20 carbon atoms, "C 1-12 alkyl" means straight and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 8, 9, 10, 11, or 12 carbon atoms, "C 1-8 alkyl" means straight and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms, "C 1-6 alkyl" means straight and branched chain alkyl groups having 1, 2, 3, 4, 5, or 6 carbon atoms, "C 1-4"Alkyl" denotes straight-chained and branched alkyl groups having 1, 2, 3 or 4 carbon atoms. The alkyl groups are, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1 -methylbutyl, 1 -ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1 -dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1 -methylpentyl, 2-ethylbutyl, 1 -ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1 -dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl and the like or their isomers. It can be monovalent (such as CH3), divalent (-CH2-) or polyvalent (such as -CH2-CH2-CH2-), depending on the number of hydrogen atoms which are replaced by the radical.

[0067] The term "C 2-12 "Alkenyl" is understood as meaning an optionally straight-chained or branched hydrocarbon radical which contains one or more double bonds and has 2 to 12 carbon atoms. "C 2-6 "Alkenyl" is understood as meaning an optionally straight-chained or branched hydrocarbon radical which contains one or more double bonds and has 2, 3, 4, 5, 6 carbon atoms, in particular 2 or 3 carbon atoms ("C 2-3 ​In case the alkenyl group contains more than one double bond, it is to be understood that the double bonds can be isolated from or conjugated to each other. The alkenyl group is, for example, ethenyl, allyl, (E)-2-methylethenyl, (Z)-2-methylethenyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1 - enyl, (Z)-but-1 -enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1 -enyl, (Z)-pent-1 -enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1 -enyl, (Z)-hex-1 -enyl, isopropenyl, 2-methylprop-2-enyl, 1 -methylprop-2-enyl, 2-methylprop-1 -enyl, (E)-1 -methylprop-1 -enyl, (Z)-1 -methylprop-1 -enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1 -methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1 -methylbut-2-enyl, (Z)-1 -methylbut-2-enyl, (E)-3-methylbut-1 -enyl, (Z)-3-methylbut-1 -enyl, (E)-2-methylbut-1 -enyl, (Z)-2-methylbut-1 -enyl, (E)-1 -methylbut-1 -enyl, (Z)-1 -methylbut-1 -enyl, 1,1 -dimethylprop-2-enyl, 1 -ethylprop-1 -enyl, 1 -propylvinyl or 1 -isopropylvinyl.

[0068] The term "C 2-12"Alkynyl" is understood to mean a straight-chain or branched one valent hydrocarbon radical, which contains one or more triple bonds and has 2 to 12 carbon atoms, optionally "C2-C6-alkynyl". The term "C2-C6-alkynyl" is understood to mean optionally a straight-chain or branched one valent hydrocarbon radical, which contains one or more triple bonds and has 2, 3, 4, 5, 6 carbon atoms, in particular 2 or 3 carbon atoms ("C2-C3-alkynyl"). Said alkynyl group is, for example, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 2-methylpent-3-ynyl, 1-methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methylpent-2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl, 1-ethylbut-3-ynyl, 1-ethylbut-2-ynyl, 1-propylprop-2-ynyl, 1-isopropylprop-2-ynyl, 2,2-dimethylbut-3-ynyl, 1,1-dimethylbut-3-ynyl, 1,1-dimethylbut-2-ynyl or 3,3-dimethylbut-1-ynyl. In particular, said alkynyl group is ethynyl, prop-1-ynyl or prop-2-ynyl.

[0069] The term "heteroalkyl", by itself or in combination with another term, means a stable straight-chain or branched-chain alkyl radical consisting of the stated number of carbon atoms and at least one heteroatom or heteroatom group. In some embodiments, the heteroatom is selected from B, O, N, and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen heteroatom is optionally quaternized. In other embodiments, the heteroatom group is selected from -C(=O)O-, -C(=O)-, -C(=S)-, -S(=O), -S(=O)2-, -C(=O)N(H)-, -N(H)-, -C(=NH)-, -S(=O)2N(H)-, and -S(=O)N(H)-. In some embodiments, the heteroalkyl is C 1-6 heteroalkyl; in other embodiments, the heteroalkyl is C 1-3Heteroalkyl. The heteroatom or heteroatom group can be located at any internal position of the heteroalkyl group, including the position at which the alkyl group is attached to the rest of the molecule, although the terms "alkoxy," "alkylamino," and "alkylthio" (or thioalkoxy) are meant to refer only to those alkyl groups attached to the remainder of the molecule through an oxygen, amino, or sulfur atom, respectively. Examples of heteroalkyl include, but are not limited to, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH2(CH3)2, -CH2-CH2-O-CH3, -NHCH3, -N(CH3)2, -NHCH2CH3, -N(CH3)(CH2CH3), -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -SCH3, -SCH2CH3, -SCH2CH2CH3, -SCH2(CH3)2, -CH2-SCH2-CH3, -CH2-CH2, -S(=O)-CH3, -CH2-CH2-S(=O)2-CH3. Up to two heteroatoms can be consecutive, such as, for example, -CH2-NH-OCH3.

[0070] The term "heteroalkenyl," by itself or in combination with another term, means, unless otherwise indicated, a stable straight or branched chain hydrocarbon radical, or combination thereof, consisting of at least one carbon atom and at least one heteroatom, which contains at least one double bond and which can be substituted as set forth herein.

[0071] The term "heteroalkynyl," by itself or in combination with another term, means, unless otherwise indicated, a stable straight or branched chain hydrocarbon radical, or combination thereof, consisting of at least one carbon atom and at least one heteroatom, which contains at least one triple bond and which can be substituted as set forth herein.

[0072] The term "aryl" means a cyclic aromatic hydrocarbon radical having 1 to 3 aromatic rings (including monocyclic or bicyclic or tricyclic radicals), such as phenyl, biphenyl, or naphthyl. When containing two aromatic rings (bicyclic, etc.), the aromatic rings of the aryl radical are optionally connected at a single point (e.g., biphenyl) or fused (e.g., naphthyl). The term "C 6-14 aryl" is understood to mean a monovalent aromatic monocyclic, bicyclic, or tricyclic hydrocarbon ring ("C 6-14 aryl") having 6, 7, 8, 9, 10, 11, 12, 13, or 14 carbon atoms, optionally "C 6-12 aryl", in particular a ring having 6 carbon atoms ("C6aryl"), such as phenyl; or a bicyclic ring having 10 carbon atoms ("C 10 aryl"), such as naphthyl; or a tricyclic ring having 13 carbon atoms ("C 13 aryl"), such as fluorenyl; or a tricyclic ring having 14 carbon atoms ("C 14 aryl"), such as anthracenyl. Attached Figure Description

[0073] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0074] Figure 1 The product of Example 1 is (2-benzo-[d]-thiazolyl)(phenyl)-λ 3 -Iodotrifluoroacetate 2-1 1 HNMR spectrum;

[0075] Figure 2 The product of Example 1 is (2-benzo-[d]-thiazolyl)(phenyl)-λ 3 -Iodotrifluoroacetate 2-1 19 FNMR spectrum;

[0076] Figure 3 The product of Example 1 is (2-benzo-[d]-thiazolyl)(phenyl)-λ 3 -Iodotrifluoroacetate 2-1 13 CNMR spectrum;

[0077] Figure 4 It is product 2-perfluorotert-butoxybenzo-[d]-thiazole 3-1 from Example 1. 1 H NMR spectrum;

[0078] Figure 5 It is product 2-perfluorotert-butoxybenzo-[d]-thiazole 3-1 from Example 1. 19 F NMR spectrum;

[0079] Figure 6 It is product 2-perfluorotert-butoxybenzo-[d]-thiazole 3-1 from Example 1. 13 C NMR spectrum;

[0080] Figure 7 This is product 2-perfluorotert-butoxy-3-methylbenzo-[d]-thiazolyl-3-onium trifluoromethanesulfonate 1-1 from Example 1. 1 H NMR spectrum;

[0081] Figure 8 This is product 2-perfluorotert-butoxy-3-methylbenzo-[d]-thiazolyl-3-onium trifluoromethanesulfonate 1-1 from Example 1. 19 F NMR spectrum;

[0082] Figure 9 This is product 2-perfluorotert-butoxy-3-methylbenzo-[d]-thiazolyl-3-onium trifluoromethanesulfonate 1-1 from Example 1. 13C NMR spectrum;

[0083] Figure 10 is the product of Example 2, (E)-4-(2-perfluoro-tert-butyivinyl) biphenyl 1 H NMR spectrum;

[0084] Figure 11 is the product of Example 2, (E)-4-(2-perfluoro-tert-butyivinyl) biphenyl 19 F NMR spectrum;

[0085] Figure 12 is the product of Example 2, (E)-4-(2-perfluoro-tert-butyivinyl) biphenyl 13 C NMR spectrum;

[0086] Figure 13 is the product of Example 3, (Z)-4-(2-perfluoro-tert-butyivinyl) biphenyl 1 H NMR spectrum;

[0087] Figure 14 is the product of Example 2, (Z)-4-(2-perfluoro-tert-butyivinyl) biphenyl 19 F NMR spectrum;

[0088] Figure 15 is the product of Example 2, (Z)-4-(2-perfluoro-tert-butyivinyl) biphenyl 13 C NMR spectrum. DETAILED DESCRIPTION

[0089] The examples described below by reference to the accompanying drawings are exemplary and are intended to serve only to explain the present application and cannot be understood as limiting the present application.

[0090] The present application is abbreviated as follows:

[0091] PIFA stands for bis(trifluoroacetyloxy)iodobenzene;

[0092] DCM stands for dichloromethane;

[0093] fac-Irppy3 stands for fac-tris(2-phenylpyridine)iridium;

[0094] CuTC stands for copper thien-2-carboxylate;

[0095] r.t. stands for room temperature;

[0096] Chloroform-d stands for deuterated chloroform.

[0097] The chemical reaction equation for the synthesis of 2-perfluoro-tert-butoxy-3-methylbenzo-[d]-thiazolium triflate in the present application is as follows:

[0098]

[0099] Example 1: Synthesis of radical-type perfluoro-t-butylating reagent 1-1:

[0100] First step, 1.0 equivalent of PIFA (bis-trifluoroacetoxyiodobenzene, 100 mmol, 43.0 g) was placed in 100 mL of dichloromethane to form a suspension at room temperature. 1.0 equivalent of 2-trimethylsilanylbenzo-[d]-thiazole (mass fraction 92%, 100 mmol, 22.5 g) was added dropwise to the above suspension at room temperature under magnetic stirring. The suspension gradually turned into a homogeneous solution, which was stirred at room temperature for 1 hour. At this time, white solid precipitated in the solution, and 100 mL of n-pentane was added to the system under magnetic stirring, and the precipitated solid in the solution increased. The mixture was cooled to -20 degrees Celsius, which further promoted the precipitation of solid. Filtration was performed, and the filter cake was washed with ice n-pentane until white. (2-benzo-[d]-thiazolyl)(phenyl)-λ 3 -iodotri fluoroacetate 2-1 (white solid, 73%, 32.9 g);

[0101]

[0102] 1 H NMR (400 MHz, Chloroform-d) δ 8.17 (d, J = 8.1 Hz, 2H), 8.08 (d, J = 7.7 Hz, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.59 (t, J = 7.5 Hz, 1H), 7.54 - 7.41 (m, 4H).

[0103] 13 C NMR (101 MHz, Chloroform-d) δ 162.21 (q, J = 35.4 Hz), 153.42, 138.19, 135.45, 132.37, 131.93, 127.32, 127.27, 124.23, 121.47, 118.98, 115.86 (q, J = 293.9 Hz).

[0104] 19 F NMR (376 MHz, Chloroform-d) δ -75.04 (s, 3F).

[0105] Second step, under nitrogen atmosphere and magnetic stirring, 1.2 equivalents of perfluoro-tert-butyl alcohol (60 mmol, 14.1 g) were dissolved in 60 mL of THF to prepare a 1.0 mol / L solution, then the solution was cooled to 0°C and 1.2 equivalents of n-butyllithium in hexane (1.6 M, 60 mmol, 37.5 mL) were added dropwise slowly. The reaction was continued at 0°C for 10 minutes, then 1.0 equivalent of (2-benzo-[d]-thiazolyl)(phenyl)-lambda 3 - Iodotricfluoroacetate 2-1 (50 mmol, 22.6 g) was added to the solution, the cooling device was removed and the mixture was heated to 60°C for 24 hours. Upon return to room temperature, the solvent was removed by rotary evaporation, then flash column chromatography (petroleum ether - petroleum ether / ethyl acetate = 200 / 1) gave 2-perfluoro-tert-butoxybenzo-[d]-thiazole 3-1 (white solid, 73%, 13.5 g);

[0106]

[0107] 1 H NMR (400 MHz, Chloroform-d) δ 7.91 (d, J = 8.3 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.57 - 7.45 (m, 1H), 7.43 - 7.37 (m, 1H).

[0108] 13 C NMR (101 MHz, Chloroform-d) δ 164.94, 148.04, 133.52, 126.67, 125.53, 123.05, 121.33, 119.82 (q, J = 293.9 Hz), 83.32 - 81.74 (m).

[0109] 19 F NMR (376 MHz, Chloroform-d) δ -69.04 (s, 9F).

[0110] Third step, 1.0 equivalent of 2-perfluoro-tert-butoxybenzo-[d]-thiazole 3-1 (30 mmol, 11.1 g) was dissolved in 30 mL of dichloromethane (1.0 mol / L concentration), then 1.3 equivalents of methyl triflate (39 mmol, 4.0 mL) were added, heated to 80°C and refluxed for 18 hours, cooled to room temperature, ethyl ether was added to the mixture, cooled to -20°C, filtered and the white solid obtained was washed with a small amount of ethyl ether to obtain 2-perfluoro-tert-butoxy-3-methylbenzo-[d]-thiazolium triflate 1-1 (white solid, 92%, 14.7 g).

[0111]

[0112] 1 H NMR (400 MHz, Acetonitrile-d3) δ 8.29 (d, J = 8.2 Hz, 1H), 8.12 (d, J = 9.1 Hz, 1H), 7.99 - 7.93 (m, 1H), 7.89 - 7.83 (m, 1H), 4.14 (s, 3H).

[0113] 13 C NMR (101 MHz, Acetonitrile-d3) δ 169.77, 136.41, 131.03, 130.19, 124.86, 124.72, 121.14 (q, J = 322.2 Hz), 118.74 (q, J = 292.9 Hz), 117.29, 84.52 - 83.54 (m), 35.65.

[0114] 19 F NMR (376 MHz, Acetonitrile-d3) δ -69.05 (s, 9F), -79.31 (s, 3F).

[0115] Example 2: Synthesis of (E)-4-(2-perfluoro-tert-butylvinyl)biphenyl:

[0116]

[0117] Into a 25 mL Schlenk tube, a stir bar, p-phenylstyrene (1.0 eq, 0.1 mmol, 18.0 mg), fac-Irppy3 (2%, 0.002 mmol, 1.3 mg), cuprous thiophene-2-carboxylate (10%, 0.01 mmol, 1.9 mg), compound 1-1 (1.3 eq, 0.13 mmol, 69 mg) and 1 mL dichloromethane were added under nitrogen protection, then the reaction tube was placed under a 10 W wavelength 425 nm LED light for 4 hours. After the reaction was completed, the organic solvent was removed by rotary evaporation, and the product (E)-4-(2-perfluoro-tert-butylvinyl)biphenyl (white solid, 72%, 28.7 mg) was separated by flash column chromatography (petroleum ether).

[0118]

[0119] 1H NMR (400 MHz, Chloroform-d) δ 7.67 - 7.58 (m, 4H), 7.57 - 7.51 (m, 2H), 7.50 - 7.42 (m, 2H), 7.42 - 7.35 (m, 1H), 7.18 (d, J = 16.8 Hz, 1H), 6.14 (d, J = 16.8 Hz, 1H).

[0120] 13 C NMR (101 MHz, Chloroform-d) δ 142.77, 140.29, 140.21, 133.60, 129.00, 127.92, 127.68, 127.66, 127.14, 121.63 (q, J = 290.0 Hz), 110.36, 60.87 - 60.06 (m).

[0121] 19 F NMR (376 MHz, Chloroform-d) δ -65.67 (s, 9F).

[0122] Example 3: Synthesis of (Z)-4-(2-perfluoro-tert-butylethenyl)biphenyl:

[0123]

[0124] Into a 25 mL Schlenk tube was added a stir bar, p-phenylstyrene (1.0 eq, 0.1 mmol, 18.0 mg), fac-Irppy3((2%, 0.002 mmol, 1.3 mg), cuprous thiophene-2-carboxylate (10%, 0.01 mmol, 1.9 mg), compound 1-1 (1.3 eq, 0.13 mmol, 69 mg), cesium carbonate (2.0 eq, 0.2 mmol, 65 mg) and 1 mL of dichloromethane under nitrogen protection, then the reaction tube was placed under a 10 W wavelength 425 nm LED for 4 hours of light. After the reaction was completed, the organic solvent was removed by rotary evaporation, and the product (Z)-4-(2-perfluoro-tert-butylethenyl)biphenyl (white solid, 78%, 31.1 mg) was obtained by flash column chromatography (petroleum ether).

[0125]

[0126] 1 H NMR (400 MHz, Chloroform-d) δ 7.62 (d, J = 7.3 Hz, 2H), 7.58 (d, J = 8.3 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.39 - 7.33 (m, 2H), 7.21 (d, J = 8.3 Hz, 2H), 5.77 (d, J = 13.3 Hz, 1H).

[0127] 13 C NMR (101 MHz, Chloroform-d) δ 142.23, 140.56, 140.55, 134.09, 128.89, 127.82, 127.58, 127.12, 126.46, 121.34 (q, J = 289.9 Hz), 113.33, 60.92 - 60.10 (m).

[0128] 19 F NMR (376 MHz, Chloroform-d) δ -64.72 (s, 9F).

[0129] In the description of the present specification, the description of the terms "one embodiment", "some embodiments", "an example", "a specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Also, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. In addition, the person skilled in the art can combine and combine the different embodiments or examples described in the present specification and the features of the different embodiments or examples without contradiction.

[0130] Although the embodiments of the present application have been shown and described above, it is understood that the above-described embodiments are exemplary and are not to be construed as limiting the present application, and those skilled in the art can make changes, modifications, replacements and variations to the above-described embodiments within the scope of the present application.

Claims

1. A perfluoro-tert-butylation reagent characterized by, The perfluoro-tert-butylation reagent has a structure as shown in Formula 1, the dashed line in the represents the presence or absence of a phenyl group; R 1 R is H, alkyl, cycloalkyl, cycloalkylalkyl, Y is S; X is triflate, tetrafluoroborate, hexafluorophosphate or triflate; R 2 is H or alkyl.

2. A process for preparing a compound of formula (1) ###0002### (1) characterized in that, comprising: substituting a compound represented by formula (3) with R 1 X to obtain a compound represented by formula (1), ， ， wherein R is an alkyl group; and 1 an alkyl group; and Y is S; X is triflate, tetrafluoroborate, hexafluorophosphate or triflate; R 2 is H or alkyl.

3. The method of claim 2, wherein, The compound shown in Formula (3) is obtained by reacting a compound shown in Formula (2) with perfluoro-tert-butanol, 。 4. The method of claim 2, wherein, The compound shown in Formula (2) is obtained by reacting a compound shown in Formula (4) with bis-trifluoroacetoxyiodobenzene, The compound shown in Formula (3) is obtained by reacting a compound shown in Formula (2) with perfluoro-tert-butanol, The compound shown in Formula (2) is obtained by reacting a compound shown in Formula (4) with bis-trifluoroacetoxyiodobenzene, The compound shown in Formula (3) is obtained by reacting a compound shown in Formula (2) with perfluoro-tert-butanol, The compound shown in Formula (2) is obtained by reacting a compound shown in Formula (4) with bis-trifluoroacetoxyiodobenzene, The compound shown in Formula (3) is obtained by reacting a compound shown in Formula (2) with perfluoro-tert-butanol, The compound shown in Formula (2) is obtained by reacting a compound shown in Formula (4) with bis-trifluoroacetoxyiodobenzene, The compound shown in Formula (3) is obtained by reacting a 。

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