Perfluoro tert-butylation reagent and preparation method thereof

Abstract

The invention provides a perfluoro tert-butylation reagent and a preparation method thereof. The perfluoro tert-butylation reagent has a structure as shown in a formula 1. The reagent can realize controllable perfluoro tert-butylation reaction of an organic substrate, so that a series of novel perfluoro tert-butyl compounds are mildly and efficiently prepared. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a perfluoro tert-butylating agent and a preparation method thereof. Background Art

[0002] Fluoroalkylation has attracted extensive attention in the past two or three decades due to the wide application of fluoroalkyl-containing compounds in drug development and organic functional material design. In order to introduce fluoroalkyl groups into organic molecules, a series of fluoroalkylation reagents (such as Togni reagent, Umemoto reagent, Chen reagent, etc.) have been developed. According to the reactivity of fluoroalkyl groups, these reagents can be further classified into electrophilic, nucleophilic and free radical types.

[0003] The most widely studied perfluoroalkylation reaction at present is undoubtedly the trifluoromethylation reaction. On the one hand, this is because trifluoromethyl compounds play an important role in changing the lipid solubility and electrostatic potential of molecules (fluorine effect). On the other hand, the trifluoromethyl group is the smallest and most basic structural unit of the perfluoroalkyl group, and studying its properties is of the most universal significance. In recent years, many groups have been reported to function as "super trifluoromethyl" (such as perfluoroisopropyl and perfluorotert-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" groups, the perfluorotert-butylation reaction has its special appeal. This is because its nine chemically equivalent fluorine atoms bring additional unique 19 F-NMR properties, which makes perfluorotert-butyl compounds have great application value in sensing and imaging.

[0004] However, due to the strong spatial and electronic effects of perfluoro-tert-butyl itself, the perfluoro-tert-butylation reaction of organic molecules faces great difficulties. The current mature method for introducing perfluoro-tert-butyl fragments is based on the Mitsunobu reaction of perfluoro-tert-butyl alcohol (i.e., perfluoro-tert-butoxylation).

[0005] Nucleophilic perfluoro-tert-butyl reagents based on perfluoro-tert-butyl anions were reported in the last century. However, most common fluorinated small molecules used to prepare perfluoro-tert-butyl anions are highly toxic and unstable. Due to the lack of stable, safe and accessible reagents, the perfluoro-tert-butyl reaction has not made substantial progress until recent years: in 2021, the literature reported the first method for preparing perfluoro-tert-butyl cesium from a stable and safe precursor, and used this unstable species in nucleophilic substitution reactions with "alkyl-leaving groups" and activated perfluoroaromatics to prepare a series of sp 2 / sp 3C-perfluoro-tert-butyl compounds (Angew. Chem. Int. Ed., 2021, 60, 27318–27323.); in 2022, the literature used hypofluorite to oxidize perfluoro-tert-butyl sulfide to form perfluoro-tert-butyl sulfone compounds, and the regioselective nucleophilic perfluoro-tert-butyl reaction of benzyne was achieved through perfluoro-tert-butyl sulfone (J. Am. Chem. Soc., 2022, 144, 48, 22281–22288.).

[0006] Electrophilic / radical reactions have not been widely studied, mainly due to the lack of corresponding perfluoro-tert-butylating agents. Previously, perfluoro-tert-butyl halides have been shown to provide perfluoro-tert-butyl radicals, but most perfluoro-tert-butyl halides are low-boiling, highly toxic compounds, and the synthesis steps are complicated, so they lack practical value.

[0007] In summary, the current perfluoro-tert-butylation reactions of organic molecules focus on the nucleophilic reaction between perfluoro-tert-butyl anions and highly active reaction substrates.

[0008] In recent years, the cleavage of the carbon-oxygen bond of alcohols has gradually become an important way to achieve alkylation reactions. As the only commercially available perfluoro-tert-butyl compound, perfluoro-tert-butyl alcohol has extremely weak nucleophilicity and is often used as an organic solvent. The corresponding anion is often used as a counter anion of imidazole-type ionic liquids. The strong electronic and steric effects make the carbon-oxygen bond of perfluoro-tert-butyl alcohol extremely difficult to activate. Therefore, using perfluoro-tert-butyl alcohol as a perfluoro-tert-butyl source to develop perfluoro-tert-butylating agents is extremely valuable and challenging. Summary of the invention

[0009] The purpose of the present invention is to solve the limitations of the current perfluoro tert-butylation reaction and develop a new perfluoro tert-butylation reagent: a perfluoro tert-butoxy substituted azaaromatic ring onium salt. By utilizing the unique reactivity of the reagent, the perfluoro tert-butylation reaction of organic small molecules such as alkenes, alkynes, and aromatic rings can be achieved. In particular, the reagent raw materials used in the present invention are cheap and easy to obtain, convenient for large-scale preparation and can be stored stably for a long time, and are available perfluoro tert-butylation reagents. According to an embodiment of the present invention, the present invention proposes a strong electrophilic reagent based on a nitrogen heteroaromatic ring skeleton, which is reacted with perfluoro tert-butanol to further selectively activate the carbon-oxygen bond. According to an embodiment of the present invention, the present invention starts from PIFA (bistrifluoroacetoxy iodobenzene, commercially available), designs and synthesizes a class of highly active azaaromatic high-valent iodine (III) reagents, highly selectively realizes carbon-oxygen coupling with perfluoro tert-butanol anions, and develops a certain available perfluoro tert-butylation reagent based on this. By using the reagent, the present invention realizes the perfluoro tert-butylation reaction of olefins, alkynes and aromatic ring substrates, and a series of novel perfluoro tert-butyl compounds are controllably obtained.

[0010] In the first aspect of the present invention, the present invention provides a perfluoro tert-butylating agent. According to an embodiment of the present invention, the perfluoro tert-butylating agent has a structure as shown in Formula 1,

[0011]

[0012] The dashed lines in the graph represent 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 trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate or trifluoroacetate;

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

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

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

[0020] According to an embodiment of the present invention, the structure of the perfluoro tert-butylating agent is The remaining variables are as defined in the present invention.

[0021] In another aspect of the present invention, the present invention also provides a method for preparing the compound represented by formula (1). According to an embodiment of the present invention, the method comprises:

[0022] The compound represented by formula (3) and R 1 X undergoes a substitution reaction to obtain a compound represented by formula (1),

[0023]

[0024] Among them, 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 alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl;

[0027] X is trifluoromethanesulfonate, 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 invention, the compound represented by formula (3) is obtained by reacting the compound represented by formula (2) with perfluoro-tert-butyl alcohol.

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

[0031] According to an embodiment of the present invention, the compound represented by formula (2) is obtained by reacting the compound represented by formula (4) with bis(trifluoroacetyloxyiodobenzene).

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

[0033] According to an embodiment of the present invention, the compound structure represented by formula (1) is The remaining variables are as defined in the present invention.

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

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

[0036] According to an embodiment of the present invention, the compound structure represented by formula (1) is The remaining variables are as defined in the present invention.

[0037] In another aspect of the present invention, the present invention also provides a method for preparing the above-mentioned perfluoro tert-butylating agent. According to an embodiment of the present invention, the method adopts the synthesis route shown in the figure:

[0038]

[0039] The specific synthesis steps are as follows:

[0040]

[0041] In the first step, PIFA (bis(trifluoroacetoxyiodobenzene)) is placed in dichloromethane at room temperature. At room temperature, the aryl silicide is slowly added dropwise to the above suspension under magnetic stirring. The suspension gradually becomes a uniform solution and is stirred at room temperature for 1 hour. At this time, a white solid precipitates in the solution. A low-polarity solvent equal in volume to the solvent is added to the system under magnetic stirring, and the amount of solid precipitated in the solution increases. The mixture is cooled to -20 degrees Celsius to further promote solid precipitation. Filter and wash the filter cake with a low-polarity solvent until it turns white to obtain (aryl)(phenyl)-λ 3 -iodotrifluoroacetate 2;

[0042]

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

[0044]

[0045] In the third step, the perfluoro-tert-butoxy compound 3 is dissolved in dichloromethane, and then an electrophilic reagent R is added. 1 X, heating to reflux, cooling to room temperature, adding a low polarity solvent to the mixture, cooling to -20 degrees Celsius, filtering, and washing the obtained solid with a small amount of low polarity solvent to obtain compound 1.

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

[0047] According to an embodiment of the present invention, in the first step, the ratio of PIFA to aryl silicide is 2 / 1 to 1 / 2, and the remaining variables are as defined in the present invention.

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

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

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

[0051] According to the embodiments of the present invention, the present invention has at least one of the following beneficial effects:

[0052] The perfluoro tert-butylation reagent provided in this article is cheap and easy to obtain, can be prepared in large quantities, and can be stored stably for a long time. It 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 mildly achieved to prepare new perfluoro tert-butyl compounds with high added value.

[0053] In the process of preparing the reagent, the present invention develops a new class of highly active nitrogen heteroaryl hypervalent iodine (III) reagents based on PIFA, which can highly selectively transfer nitrogen heteroaryl groups without transferring the benzene ring. The previous literature on the perfluoro-tert-butoxylation reaction based on the hypervalent iodine strategy requires the use of a specific "non-transfer group" (Org. Lett., 2019, 21, 13, 5206-5210.).

[0054] Definition and explanation of terms

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

[0056] In this article, the term "optionally" means that the feature exists or does not exist, which means that the event described later can but does not necessarily occur, thus including two types of situations where the event occurs or does not occur. For example, "optionally a heterocyclic group substituted with an alkyl group" means that the alkyl group can but does not necessarily exist, thus including situations where the heterocyclic group is substituted with an alkyl group and a heterocyclic group is not substituted with an alkyl group.

[0057] As described herein, the compounds of the present invention may contain "optionally substituted" moieties. In general, the term "substituted", whether or not preceded by the term "optionally", means that one or more hydrogens of the specified moiety are replaced by suitable substituents. Unless otherwise indicated, an "optionally substituted" group may have a suitable substituent at each substitutable position of the group, and when multiple positions in any given structure may be substituted by multiple substituents selected from a specified group, the substituents at each position may be the same or different. The combination of substituents contemplated by the present invention is preferably a combination of substituents that allows the formation of stable or chemically feasible compounds. As used herein, the term "stable" refers to a compound that does not substantially change when subjected to conditions that allow it to be manufactured, detected, and in certain embodiments, recovered, purified, and used for one or more purposes disclosed herein.

[0058] Each optional substituent on a substitutable carbon is independently selected from the following monovalent substituents: =O; cyano; C 1-6 Alkyl; C 2-6 Alkenyl; C 2-6 Alkynyl; HaloC 1-6 Alkyl, C 1-6 Alkoxy; Halogen; -(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 may be substituted by Ro; -(CH2) 0-4 O(CH2) 0-1 Ph, which may be substituted by Ro; -CH=CHPh, which may be substituted by Ro; -(CH2) 0-4 O(CH2)0-1-pyridyl, which may be substituted by 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 alkylene)ON(Ro)2; or -(C 1-4 Straight chain or branched alkylene) C(O)ON(Ro)2.

[0059] Each Ro is independently hydrogen, C 1-6 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph, -CH2-(5-6 membered heteroaromatic ring) or a 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, or, regardless of the above definition, two single occurrences of Ro together with one or more intervening atoms 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 may be substituted on the saturated carbon atoms of Ro by a divalent substituent selected from =O and =S; or each Ro is optionally substituted by a monovalent substituent independently selected from the following: halogen, -(CH2) 0-2 R, -(halogen R), -(CH2) 0-2 OH, -(CH2) 0-2 OR, -(CH2)0-2 CH(OR)2, -O(halogen R), -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, -(C1-4 linear or branched alkylene)C(O)OR or -SSR.

[0060] Each R is independently selected from C 1-4 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph, 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, in the case of a preceding halogen, is substituted only by one or more halogens; or wherein the optional substituents on the saturated carbon are divalent substituents independently selected from the following: =O, =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 attached to the adjacent substitutable carbon of the "optionally substituted" group is -O(CR*2) 2-3 O-, wherein each individual occurrence of R* is selected from hydrogen, a C1-6 aliphatic group, or an unsubstituted 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0061] When R* is a C1-6 aliphatic group, R* is optionally substituted by 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 a C1-4 aliphatic group, -CH2Ph, -O(CH2), 0-1 Ph, 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, in the case of a preceding halo, substituted only by one or more halogens.

[0062] Optional substituents on the substitutable nitrogen are independently:

[0063]

[0064] Among them is independently hydrogen, a C1-6 aliphatic group, unsubstituted -OPh, or an unsubstituted 5-6 membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, or two single occurrences of Together with one or more of its intervening atoms, it forms an unsubstituted 3-12 membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; wherein when When it is a C1-6 aliphatic group, Optionally substituted by 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 C1-4 aliphatic group, -CH2Ph, -O(CH2)0-1Ph 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, in the case of a halogen group being preceded, is substituted only by one or more halogens.

[0065] Unless otherwise specified, the numerical ranges recorded in this specification and claims are equivalent to recording at least each specific integer value therein. For example, the numerical range "1-12" is equivalent to recording each integer value in the numerical range "1-12", that is, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.

[0066] The term "C 1-20 The term "alkyl" is understood to mean straight-chain and branched alkyl groups having 1 to 20 carbon atoms. 1-12 "Alkyl" means straight chain and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 8, 9, 10, 11 or 12 carbon atoms. 1-8 "Alkyl" means straight chain and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms. 1-6 "Alkyl" means straight chain and branched chain alkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms. 1-4The term "alkyl" refers to straight-chain and branched alkyl groups having 1, 2, 3 or 4 carbon atoms. The alkyl group is, 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 or the like or isomers thereof. It may be monovalent (e.g., CH3), divalent (-CH2-) or polyvalent (e.g., divalent ).

[0067] The term "C 2-12 "Alkenyl" is understood to mean a linear or branched monovalent hydrocarbon radical containing one or more double bonds and having 2 to 12 carbon atoms. 2-6 "Alkenyl" is understood to mean optionally a linear or branched monovalent hydrocarbon radical containing one or more double bonds and having 2, 3, 4, 5, 6 carbon atoms, in particular 2 or 3 carbon atoms ("C 2-3"alkenyl"), it being understood that, in the case where the alkenyl contains more than one double bond, the double bonds may be separated from one another or conjugated. The alkenyl is, for example, vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, (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, -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-hexenyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent ...1-enyl, (Z)-pent-1-enyl, isopropenyl, 2-hexenyl, (E)-pent-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 The invention can be substituted with vinyl or 1-isopropylvinyl, or a mixture of vinyl and 1-isopropylvinyl. The invention can be substituted with vinyl or 1-isopropylvinyl, or a mixture of vinyl and 1-isopropylvinyl.

[0068] The term "C 2-12The term "alkynyl" is understood as meaning a linear or branched monovalent hydrocarbon radical which contains one or more triple bonds and has 2 to 12 carbon atoms, optionally a "C2-C6-alkynyl" radical. The term "C2-C6-alkynyl" is understood as optionally meaning a linear or branched monovalent 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"). The alkynyl radical 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, 2-methyl -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-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 In some embodiments, the alkynyl group is ethynyl, prop-1-ynyl or prop-2-ynyl.

[0069] The term "heteroalkyl" by itself or in combination with another term refers to a stable straight or branched alkyl radical or combination thereof consisting of a certain 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 In other embodiments, the heteroalkyl group is C 1-3Heteroalkyl. The heteroatom or heteroatom group may be located at any interior position of the heteroalkyl group, including the position at which the alkyl group is attached to the remainder of the molecule, but the terms "alkoxy," "alkylamino," and "alkylthio" (or thioalkoxy) are conventional expressions and refer to those alkyl groups that are attached to the remainder of the molecule through an oxygen, amino, or sulfur atom, respectively. Examples of heteroalkyl include, but are not limited to, -OCH, -OCHCH, -OCHCHCH, -OCH(CH), -CH-CH-O-CH, -NHCH, -N(CH), -NHCHCH, -N(CH)(CHCH), -CH-CH-NH-CH, -CH-CH-N(CH)-CH, -SCH, -SCHCH, -SCHCHCH, -SCH(CH), -CH-SCH-CH, -CH-CH, -S(=O)-CH, -CH-CH-S(=O)-CH. Up to two heteroatoms may be consecutive, for example -CH-NH-OCH.

[0070] The term "heteroalkenyl" by itself or in combination with another term refers to a monovalent hydrocarbon radical consisting of a certain number of carbon atoms and at least one heteroatom or heteroatom group, a stable straight or branched chain alkyl radical or combinations thereof, containing one or more double bonds.

[0071] The term "heteroalkynyl" by itself or in combination with another term refers to a monovalent alkynyl radical of a stable straight or branched chain alkyl radical or combinations thereof consisting of a certain number of carbon atoms and at least one heteroatom or heteroatom group, which contains one or more triple bonds.

[0072] The term "aryl" means a cyclic aromatic hydrocarbon group having 1 to 3 aromatic rings (including monocyclic or bicyclic or tricyclic groups), such as phenyl, biphenyl or naphthyl. When containing two aromatic rings (bicyclic, etc.), the aromatic rings of the aryl group are optionally connected at a single point (e.g., biphenyl) or fused (e.g., naphthyl). The term "C 6-14 The term "aryl" is understood to mean a monovalent aromatic monocyclic, bicyclic or tricyclic hydrocarbon ring ("C 6-14 aryl"), optionally "C 6-12 "Aryl", especially a ring having 6 carbon atoms ("C6 aryl"), such as phenyl; or biphenyl, 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 ("C 14 "aryl"), for example anthracenyl. BRIEF DESCRIPTION OF THE DRAWINGS

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

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

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

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

[0077] Figure 4 The product of Example 1, 2-perfluoro-tert-butyloxybenzo-[d]-thiazole 3-1 1 H NMR spectrum;

[0078] Figure 5 The product of Example 1, 2-perfluoro-tert-butyloxybenzo-[d]-thiazole 3-1 19 F NMR spectrum;

[0079] Figure 6 The product of Example 1, 2-perfluoro-tert-butyloxybenzo-[d]-thiazole 3-1 13 C NMR spectrum;

[0080] Figure 7 The product of Example 1, 2-perfluoro-tert-butoxy-3-methylbenzo-[d]-thiazol-3-ium trifluoromethanesulfonate 1-1 1 H NMR spectrum;

[0081] Figure 8 The product of Example 1, 2-perfluoro-tert-butoxy-3-methylbenzo-[d]-thiazol-3-ium trifluoromethanesulfonate 1-1 19 F NMR spectrum;

[0082] Fig. 9 The product of Example 1, 2-perfluoro-tert-butoxy-3-methylbenzo-[d]-thiazol-3-ium trifluoromethanesulfonate 1-1 13C NMR spectrum;

[0083] Fig.10 The product of Example 2 (E)-4-(2-perfluoro-tert-butylvinyl)biphenyl 1 H NMR spectrum;

[0084] Fig.11 The product of Example 2 (E)-4-(2-perfluoro-tert-butylvinyl)biphenyl 19 F NMR spectrum;

[0085] Fig.12 The product of Example 2 (E)-4-(2-perfluoro-tert-butylvinyl)biphenyl 13 C NMR spectrum;

[0086] Fig.13 The product of Example 3 (Z)-4-(2-perfluoro-tert-butylvinyl)biphenyl 1 H NMR spectrum;

[0087] Fig.14 The product of Example 2 (Z)-4-(2-perfluoro-tert-butylvinyl)biphenyl 19 F NMR spectrum;

[0088] Fig.15 The product of Example 2 (Z)-4-(2-perfluoro-tert-butylvinyl)biphenyl 13 C NMR spectrum. DETAILED DESCRIPTION

[0089] The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present invention, but should not be construed as limiting the present invention.

[0090] The abbreviations of the present invention are defined as follows:

[0091] PIFA stands for bis(trifluoroacetoxyiodobenzene);

[0092] DCM stands for dichloromethane;

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

[0094] CuTC stands for cuprous thiophene-2-carboxylate;

[0095] rt stands for room temperature;

[0096] Chloroform-d stands for deuterated chloroform.

[0097] The chemical reaction equation for synthesizing 2-perfluoro-tert-butoxy-3-methylbenzo-[d]-thiazol-3-ium trifluoromethanesulfonate in the present invention is as follows:

[0098]

[0099] Example 1: Synthesis of free radical perfluoro tert-butylating agent 1-1:

[0100] In the first step, 1.0 equivalent of PIFA (bis(trifluoroacetyl)iodobenzene, 100 mmol, 43.0 g) is placed in 100 mL of dichloromethane at room temperature to form a suspension. At room temperature, 1.0 equivalent of 2-trimethylsilylbenzo-[d]-thiazole (mass fraction 92%, 100 mmol, 22.5 g) is slowly added dropwise to the above suspension under magnetic stirring. The suspension gradually becomes a uniform solution and is stirred at room temperature for 1 hour. At this time, white solids are precipitated in the solution. 100 mL of n-pentane is added to the system under magnetic stirring, and the amount of solids precipitated in the solution increases. The mixture is cooled to -20 degrees Celsius to further promote solid precipitation. Filter and wash the filter cake with ice n-pentane until it turns white. (2-Benzo-[d]-thiazolyl)(phenyl)-λ can be obtained. 3 -iodotrifluoroacetate 2-1 (white solid, 73%, 32.9 g);

[0101]

[0102] 1 H NMR (400MHz, Chloroform-d) δ8.17(d,J=8.1Hz,2H),8.08(d,J=7.7Hz,1H),7.88(d,J=7.7Hz,1H),7.59(t,J=7.5Hz,1H),7.54–7.41(m,4H).

[0103] 13 C NMR(101MHz,Chloroform-d)δ162.21(q,J=35.4Hz),153.42,138.19,135.45,13 2.37,131.93,127.32,127.27,124.23,121.47,118.98,115.86(q,J=293.9Hz).

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

[0105] In the second step, under nitrogen protection and magnetic stirring throughout the process, 1.2 equivalents of perfluorotert-butyl alcohol (60 mmol, 14.1 g) were dissolved in 60 mL of THF at room temperature to prepare a 1.0 mol / L solution, and then the solution was cooled to 0 degrees Celsius, and 1.2 equivalents of n-butyl lithium in hexane solution (1.6 M, 60 mmol, 37.5 mL) were slowly added dropwise, and the reaction was continued at 0 degrees Celsius for 10 minutes, and then 1.0 equivalents of (2-benzo-[d]-thiazolyl)(phenyl)-λ 3 -iodo trifluoroacetate 2-1 (50 mmol, 22.6 g) was added to the solution, the cooling device was removed, and the mixture was heated to 60 degrees Celsius for 24 hours. The mixture was returned to room temperature, and the solvent was removed by rotary evaporation, followed by flash column chromatography (petroleum ether-petroleum ether / ethyl acetate = 200 / 1) to obtain 2-perfluoro-tert-butoxybenzo-[d]-thiazole 3-1 (white solid, 73%, 13.5 g);

[0106]

[0107] 1 H NMR (400MHz, Chloroform-d) δ7.91(d,J=8.3Hz,1H),7.73(d,J=7.8Hz,1H),7.57–7.45(m,1H),7.43–7.37(m,1H).

[0108] 13 C NMR (101MHz, Chloroform-d) δ164.94, 148.04, 133.52, 126.67, 125.53, 123.05, 121.33, 119.82 (q, J = 293.9Hz), 83.32–81.74 (m).

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

[0110] In the 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 (concentration 1.0 mol / L), followed by the addition of 1.3 equivalents of methyl trifluoromethanesulfonate (39 mmol, 4.0 mL), heated to 80 degrees Celsius and refluxed for 18 hours, cooled to room temperature, ether was added to the mixture, cooled to -20 degrees Celsius, filtered, and the resulting white solid was washed with a small amount of glacial ether to obtain 2-perfluoro-tert-butoxy-3-methylbenzo-[d]-thiazole-3-ium trifluoromethanesulfonate 1-1 (white solid, 92%, 14.7 g).

[0111]

[0112] 1 H NMR (400MHz, Acetonitrile-d3) δ8.29(d,J=8.2Hz,1H),8.12(d,J=9.1Hz,1H),7.99–7.93(m,1H),7.89–7.83(m,1H),4.14(s,3H).

[0113] 13 C NMR(101MHz, Acetonitrile-d3)δ169.77,136.41,131.03,130.19,124.86,124.72 ,121.14(q,J=322.2Hz),118.74(q,J=292.9Hz),117.29,84.52–83.54(m),35.65.

[0114] 19 F NMR(376MHz, 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] Under nitrogen protection, a stirring 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 of dichloromethane were added to a 25 mL Schlenk tube, and then the reaction tube was placed under a 10 W LED with a wavelength of 425 nm 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 obtained by rapid column chromatography (petroleum ether) separation.

[0118]

[0119] 1H NMR (400MHz, Chloroform-d) δ7.67–7.58(m,4H),7.57–7.51(m,2H),7.50–7.42(m,2H),7.42–7.35(m,1H),7.18(d,J=16.8Hz,1H),6.14(d,J=16.8Hz,1H).

[0120] 13 C NMR(101MHz,Chloroform-d)δ142.77,140.29,140.21,133.60,129.00,127.9 2,127.68,127.66,127.14,121.63(q,J=290.0Hz),110.36,60.87–60.06(m).

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

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

[0123]

[0124] Under nitrogen protection, a stirring 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 were added to a 25 mL Schlenk tube, and then the reaction tube was placed under a 10 W LED with a wavelength of 425 nm for 4 hours. After the reaction was completed, the organic solvent was removed by rotary evaporation, and the product (Z)-4-(2-perfluoro-tert-butylvinyl)biphenyl (white solid, 78%, 31.1 mg) was obtained by rapid column chromatography (petroleum ether) separation.

[0125]

[0126] 1 H NMR(400MHz,Chloroform-d)δ7.62(d,J=7.3Hz,2H),7.58(d,J=8.3Hz,2H),7.46( t,J=7.6Hz,2H),7.39–7.33(m,2H),7.21(d,J=8.3Hz,2H),5.77(d,J=13.3Hz,1H).

[0127] 13 C NMR(101MHz,Chloroform-d)δ142.23,140.56,140.55,134.09,128.89,127.8 2,127.58,127.12,126.46,121.34(q,J=289.9Hz),113.33,60.92–60.10(m).

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

[0129] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0130] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A perfluoro tert-butylating agent, characterized in that: The perfluoro tert-butylating agent has a structure as shown in Formula 1, The dashed lines in the graph represent the presence or absence of a phenyl group; R 1 is alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl; Y is O, S, S=O, S(=O)2, NR Y ; R Y is alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl; X is trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate or trifluoroacetate; R 2 is H, halogen, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl.

2. The perfluoro tert-butylating agent according to claim 1, characterized in that R 1 is alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl; Optionally, R 2 is H, halogen, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl.

3. The perfluoro tert-butylating agent according to claim 1, characterized in that The structure of the perfluoro tert-butylating agent is 4. A method for preparing a compound represented by formula (1), characterized in that: include: The compound represented by formula (3) and R 1 X undergoes a substitution reaction to obtain a compound represented by formula (1), Among them, R 1 is alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl; Y is O, S, S=O, S(=O)2, NR Y ; R Y is alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl; X is trifluoromethanesulfonate, tetrafluoroborate, hexafluorophosphate or trifluoroacetate; R 2 is H, halogen, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl.

5. The method according to claim 4, characterized in that The compound represented by formula (3) is obtained by reacting the compound represented by formula (2) with perfluoro-tert-butyl alcohol.

6. The method according to claim 5, characterized in that The compound represented by formula (2) is obtained by reacting the compound represented by formula (4) with bis(trifluoroacetyloxy)iodobenzene.

7. The method according to claim 4, characterized in that The compound structure represented by formula (1) is 8. The method according to claim 4, characterized in that The compound structure represented by formula (3) is 9. The method according to claim 5, characterized in that The compound structure represented by formula (2) is 10. The method according to claim 6, characterized in that The compound structure represented by formula (1) is

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