CN107011218B - A kind of fluorine nitrogen type amination reagent, preparation method and application - Google Patents

Abstract

The invention discloses a kind of fluorine nitrogen type amination reagent, preparation method and applications.The application includes the following steps: under gas shield; in organic solvent; under the action of copper catalyst and dinitrogen ligand and alkali; fluorine nitrogen type amination reagent shown in formula I, such as Formula II compound represented and such as formula III compound represented are subjected to reaction as follows, such as formula IV compound represented is made.Fluorine nitrogen type amination reagent of the invention is under copper catalyst and the effect of dinitrogen ligand, and using alkene as substrate, by the asymmetric amine arylation reaction of alkene, with good yield, outstanding corresponding selection obtains optically active 2,2- diaryl ethylamine compounds.

Description

A kind of fluorine nitrogen type amination reagent, preparation method and application

Technical field

The present invention relates to a kind of fluorine nitrogen type amination reagent, preparation method and applications.

Background technique

The fluoro- N- alkyl sulfonamide of N- can efficiently realize the fluorine of carbanion typically as a kind of electrophilic fluorination reagent Change (J.Am.Chem.Soc.1984,106,454；US Patent 4479901), amine moieties are then made with N- alkyl sulfonamide Form as by-product, Atom economy is not high.The fluoro- N- alkyl sulfonamide of N- is as amination reagent from having not been reported.

Optically active 2,2- diaryl ethylamine compounds are widely present in drug, bioactive molecule and natural products In.The method of asymmetric synthesis for developing this kind of compound is of great significance, however the research in the field is relatively fewer at present.

In document J.Am.Chem.Soc.2004,126,1954, it was recently reported that using chiral amino alcohol as ligand, realize virtue Base lithium reagent can obtain 91%-95% for phenylethylene substrate to β-nitroethylene class compound asymmetric reduction reaction Ee value.Reaction needs to be added excess ligand, while substrate aromatic ring ortho position being required to have coordinating ground oxygen atom, thus substrate It is had certain limitations in universality.In Angew.Chem.Int.Ed.2010,49,5780, it was recently reported that using chiral diene as ligand, Under rhodium catalysis, using aryl boric acid as aryl source, the asymmetric arylation of β-nitroethylene is realized, with the ee of 61-97% Value obtains optical activity diaryl nitroethane class compound.In document Org.Lett.2015,17,2250, it was recently reported that with hand Property isoquinolin oxazoline be ligand realize the asymmetric arylation of β-nitroethylene under palladium chtalyst, can be with 81-96%'s Ee value obtains optical activity diaryl nitroethane class compound.But these reaction products are needed by hydrogenation ability It is converted into chiral 2,2- diaryl ethylamine compounds.Document J.Am.Chem.Soc.2015, in 137,999, it was recently reported that from two Aryl enamine sets out, and realizes rhodium catalysis asymmetric hydrogenation, directly obtains to high enantioselectivity chirality 2,2- ammonia diaryl Base acid derivative, but react and need using the diaryl enamine of highly functional as substrate.

Therefore, in view of above-mentioned reaction status, need to develop a kind of amination reagent, while development can go out from simple substrate Hair, such as alkene, efficiently synthesis of chiral 2 with high selectivity, the method for 2- diaryl ethylamine compounds.

Summary of the invention

The technical problem to be solved by the present invention is to the conjunctions in order to overcome prior art 2,2- diaryl ethylamine compounds At in method, substrate narrow application range needs just be converted into chirality 2,2- diaryl ethylamine compounds by hydrogenation, Or to substrate requirements harshness, the defects of needs using the diaryl enamine of highly functional as substrate, and provide a kind of fluorine nitrogen Type amination reagent, preparation method and application.Fluorine nitrogen type amination reagent of the invention copper catalyst and dinitrogen ligand effect under, Using alkene as substrate, by the asymmetric amine arylation reaction of alkene, with good yield, outstanding corresponding selection obtains light Learn active 2,2- diaryl ethylamine compounds.

The present invention mainly solves above-mentioned technical problem by the following technical programs.

The present invention provides a kind of fluorine nitrogen type amination reagents shown in formula I in preparation 2,2- diaryl ethylamine compounds Application in intermediate；

Wherein,

R¹For substituted or unsubstituted C₆-C₃₀Aryl；The substituted C₆-C₃₀Substituent group in aryl be selected from halogen, C₁-C₁₀The C that alkyl, halogen replace₁-C₁₀Alkyl, C₁-C₁₀Alkoxy andOne or more of, R^1’For C₁-C₁₀Alkane Base；When substituent group is multiple (such as 1-6, preferably 1-3), the substituent group is identical or different；

R²For C₁-C₁₀Straight chained alkyl orWherein, R^1aDefinition and R¹It is identical.

In fluorine nitrogen type amination reagent shown in formula I, R¹In, the substituted C₆-C₃₀Substituent group in aryl is preferred Selected from F, Cl, Br, I, methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl (and its isomery Body), n-hexyl (and its isomers), trifluoromethyl, pentafluoroethyl group, methoxyl group, ethyoxyl, positive propoxy, isopropoxy, positive fourth Oxygroup, isobutoxy, tert-butoxy,One or more of (such as 1-6, preferably 1-3 It is a, more preferable 1-2), when substituent group is multiple, the substituent group is identical or different.

In fluorine nitrogen type amination reagent shown in formula I, R¹In, the substituted or unsubstituted C₆-C₃₀Aryl preferably takes Generation or unsubstituted C₆-C₁₄Aryl.The substituted or unsubstituted C₆-C₁₄The preferably substituted or unsubstituted phenyl of aryl takes Generation or unsubstituted naphthalene, substituted or unsubstituted anthryl, or, substituted or unsubstituted phenanthryl.The substituted C₆-C₃₀Virtue Base is preferred

In fluorine nitrogen type amination reagent shown in formula I, R²In, the C₁-C₁₀The preferred C of straight chained alkyl₁-C₆Straight chained alkyl. The C₁-C₆The preferred methyl of straight chained alkyl, ethyl, n-propyl, normal-butyl, n-pentyl or n-hexyl.

The application preferably includes the following steps: under gas shield, in organic solvent, in copper catalyst and dinitrogen ligand Under the action of alkali, change by fluorine nitrogen type amination reagent shown in formula I, such as Formula II compound represented and as shown in formula III It closes object and carries out reaction as follows, such as formula IV compound represented is made；

Wherein,

R¹And R²Definition is as described above；

R³And R⁴It independently is substituted or unsubstituted C₆-C₃₀Aryl, or, substituted or unsubstituted C₂-C₃₀Heteroaryl；Institute The C stated₂-C₃₀Hetero atom in heteroaryl be selected from one or more of N, O and S (such as 1-6, preferably 1-3, more preferably 1-2)；When hetero atom is multiple, the hetero atom is identical or different；The substituted C₆-C₃₀Aryl and described Substituted C₂-C₃₀Substituent group is independently selected from nitro, C in heteroaryl₂-C₆Heteroaryl, C₁-C₁₀The C that alkyl, halogen replace₁- C₁₀Alkyl, C₆-C₁₄Aryl, halogen,With one or more of cyano (such as 1-6, preferably 1-3 It is a)；Wherein, the C₂-C₆Heteroaryl be that hetero atom is selected from N, O and S, hetero atom number is the C of 1-4₂-C₆Heteroaryl (such as pyridyl group, imidazole radicals, pyrazolyl, pyrrole radicals, pyrimidine radicals, thienyl, furyl, quinolyl or indyl etc.)；R⁵For C₁-C₁₀The C that alkyl, halogen replace₁-C₁₀Alkyl orR⁶And R⁷It independently is C₁-C₁₀Alkyl orWhen substituent group is multiple, the substitution is identical or different.

In the preparation method such as formula IV compound represented, the preferred nitrogen of gas in the gas shield or Argon gas.

In the preparation method such as formula IV compound represented, the preferred nitrile solvents of the organic solvent, aromatic hydrocarbons One of class solvent, halogenated aryl hydrocarbon class solvent, halogenated alkanes solvents, ketones solvent and amide solvent are a variety of.It is described The preferred acetonitrile of nitrile solvents.The preferred toluene of the aromatic hydrocarbon solvent.The preferred chlorobenzene of halogenated aryl hydrocarbon class solvent, fluorobenzene With one of benzotrifluoride or a variety of.The preferred methylene chloride of the halogenated alkanes solvents and/or dichloroethanes.Described The preferred acetone of ketones solvent.The preferred N,N-dimethylformamide of the amide solvent and/or DMAC N,N' dimethyl acetamide.Institute The mixed solvent of the organic solvent stated preferred halogenated alkanes solvents and amide solvent, the preferred 9:1-1:4 of the two volume ratio.

It is described in the preparation method such as formula IV compound represented in a preferred embodiment of the invention Organic solvent is preferably through drying process.The method of the drying can be the dry conventional method of this field organic solvent.

In the preparation method such as formula IV compound represented, the copper catalyst can be the such reaction in this field Conventional copper catalyst, preferably copper powder, cuprous iodide, stannous chloride, cuprous bromide, copper chloride, copper bromide, copper acetate, acetic acid Cuprous, four acetonitrile hexafluorophosphoric acid copper, four acetonitrile copper tetrafluoroborates, four acetonitrile copper trifluoromethanesulfcomposites, copper trifluoromethanesulfcomposite or thiophene Cuprous formate；More preferable four acetonitriles hexafluorophosphoric acid copper, four acetonitrile copper tetrafluoroborates, four acetonitrile copper trifluoromethanesulfcomposites or trifluoro methylsulphur Sour copper, most preferably four acetonitrile hexafluorophosphoric acid copper.

In the preparation method such as formula IV compound represented, the dinitrogen ligand is preferably that chiral dinitrogen is matched Body.The preferred chiral double oxazoline ligands of the chiral dinitrogen ligand

One of or a variety of, R^3a、R^3b、 R^3cAnd R^3dIt independently is C₁-C₁₀Alkyl or C₆-C₃₀The C that aryl replaces₁-C₁₀Alkyl；R^4a、R^5a、R^4bAnd R^5bIndependently be hydrogen, C₁-C₁₀Alkyl, C₆-C₃₀Aryl or R^4aAnd R^5a、R^4bAnd R^5bCoupled carbon atom is formed together C₃-C₁₀Naphthenic base；R^6a、 R^6bAnd R^6cIt independently is hydrogen, C₁-C₁₀Alkyl, halogen,Cyano, trifluoromethyl or C₆-C₃₀Aryl；R⁸For C₁-C₁₀Alkane Base；N is 1,2,3 or 4；When n is 2,3 or 4, R^6aAnd R^6bIt is identical or different.

In the preparation method such as formula IV compound represented, the alkali metal salt or phenol sodium of the alkali preferred alcohols, It is preferred that R^a-ONa、R^b-OK、R^c- OLi andOne of or it is a variety of, wherein R^a、R^bAnd R^cIndependently be methyl, Ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group or tert-butyl；R^a1、R^a2、R^a3、R^a4And R^a5It independently is hydrogen, halogen, C₁- C₁₀Alkyl orR⁹For C₁-C₁₀Alkyl.

In the preparation method such as formula IV compound represented, the temperature of the reaction can be such anti-for this field Answer conventional temperature, preferably -40~30 DEG C, more preferably -10~0 DEG C.

In the preparation method such as formula IV compound represented, this field routine is can be used in the process of the reaction Detection method (such as TLC, GC, HPLC or HNMR etc.) be monitored, generally with such as Formula II or such as formula III compound represented As the terminal of reaction when disappearance.

In the preparation method such as formula IV compound represented, the dosage of the organic solvent can not be limited specifically It is fixed, it is carried out as long as not influencing reaction.The dosage of the copper catalyst and the dinitrogen ligand can be such for this field React conventional dosage, the two molar ratio preferred 2:1-1:3, more preferable 1:2.The dosage of the copper catalyst is preferably such as formula The 1%-100% molar equivalent of II compound represented；More preferable 5%-10% molar equivalent；The dosage of the dinitrogen ligand Preferably such as the 1%-100% molar equivalent of Formula II compound represented；More preferable 10-20% molar equivalent；It is described such as formula II compound represented and described such as the preferred 1:1-1:3 of the molar ratio of formula III compound represented, more preferable 1:2.Described The dosage of fluorine nitrogen type amination reagent shown in formula I is preferably described as the 100%-400% of Formula II compound represented rubs That equivalent, more preferable 200% molar equivalent.The dosage of the alkali can be the 20%- such as Formula II compound represented 200% molar equivalent, preferably 50% molar equivalent.

In a preferred embodiment of the invention, as the preparation method of formula IV compound represented preferably includes following step It is rapid: under gas shield, copper catalyst, the mixture of dinitrogen ligand and organic solvent being tried with fluorine nitrogen type amination shown in formula I Agent, such as Formula II compound represented, such as formula III compound represented and alkali mixing, carry out the reaction, are made such as formula IV institute The compound shown.

Wherein, the mixture of the copper catalyst, dinitrogen ligand and organic solvent during the preparation process, in gas shield Lower progress.The mixed temperature is preferably at -20 DEG C~30 DEG C (such as -20 DEG C).

As formula IV compound represented preparation method in, it is described after reaction, also can further include post-processing Operation.The method of the post-processing is the post-processing approach of organic synthesis field routine.In the present invention, the post-processing It preferably includes following steps: reaction solution after reaction is diluted with ethyl acetate, wash；Organic phase drying (such as it is anhydrous Magnesium sulfate) after, it filters, after concentrating filter liquor, is further isolated and purified by rapid column chromatography.The wherein item of column chromatography Part and method are the condition and method of this field routine, and the leacheate (eluent) of use can be selected according to TLC.

The present invention also provides a kind of foregoing fluorine nitrogen type amination reagents shown in formula I in preparation 2,2- diaryl Application in ethylamine compounds.

The application preferably includes the following steps:

It (1),, will be shown in formula I under the action of copper catalyst and dinitrogen ligand and alkali in organic solvent under gas shield Fluorine nitrogen type amination reagent, such as Formula II compound represented and carry out reaction as follows such as formula III compound represented, make Obtain such as formula IV compound represented；

(2) it under gas shield, in organic solvent, under the action of reducing agent, will be taken off such as formula IV compound represented Except the reaction of sulfonyl protecting group, 2,2- diaryl ethylamine compounds shown as a formula V are made；

Wherein, R¹、R²、R³And R⁴Definition as described above；R^2’For C₁-C₁₀Straight chained alkyl or R^1a；R^1aDefinition and R¹Phase Together.

In the preparation method of 2,2- diaryl ethyl aminated compounds shown as a formula V, reaction described in step (1) Each condition is as described above.

In the preparation method of 2,2- diaryl ethyl aminated compounds shown as a formula V, in step (2), the removing The method and condition of the reaction of sulfonyl protecting group can be the method and condition of the such reaction routine in this field, under the present invention is preferred Column method and condition: the preferred alcohols solvent of the organic solvent.The preferred methanol of the alcohols solvent.The reducing agent is excellent Select magnesium powder.The preferred room temperature of the temperature of the reaction.Detection method (the example of this field routine can be used in the process of the reaction Such as TLC, GC, HPLC or HNMR) it is monitored, as the terminal of reaction when generally being disappeared using such as formula IV compound represented. The dosage of the organic solvent can be not especially limited, as long as not influencing the progress of reaction.The use of the reducing agent Amount, which generally requires, to be excessively used, the molar ratio preferred 2:1-100:1, more preferable 5:1-50:1 with such as formula IV compound represented (such as 47:1).

In step (2), it is described after reaction, the step of also can further include post-processing.The post-processing Method can be the method for organic synthesis field post-processing routine.In the present invention, the post-processing preferably includes the following steps: will Reaction solution after reaction, is separated by solid-liquid separation and (is concentrated under reduced pressure or filters), and filter cake is filtered with diatomite, ethyl acetate/first Alcohol (10:1) elution；After filtrate concentration, (eluent/leacheate can be selected according to compound TLC condition for rapid column chromatography separation It selects).

The present invention also provides a kind of fluorine nitrogen type amination reagents shown in formula I:

Wherein, R¹And R²Definition is as described above.

Fluorine nitrogen type amination reagent shown in formula I preferably following any compound:

The present invention also provides the preparation methods of the fluorine nitrogen type amination reagent shown in formula I comprising following step It is rapid: in organic solvent, compound such as shown in formula A and fluorine gas being subjected to fluorination reaction as follows, are made described such as Formulas I Shown in fluorine nitrogen type amination reagent；

Wherein, R¹And R²Definition is as described above.

The organic solvent can be the solvent of the such reaction routine in this field, preferably halogenated alkanes solvents.Described The mixed solvent of halogenated alkanes solvents preferred F-11 and chloroform.The in the mixed solvent, the trichlorine one The preferred 1:1 of the volume ratio of fluoromethane and chloroform.The dosage of the fluorine gas can be not especially limited, preferably during reacting progress It is continually fed into reaction mixture.The temperature of the fluorination reaction can be conventional for the such reaction in this field temperature, preferably -78 ℃.The fluorination reaction carry out can according to this field routine detection method (such as TLC, GC, HPLC or HNMR etc.) into Row monitoring, as the terminal of reaction when generally being disappeared using such as compound shown in formula A.The time of the fluorination reaction preferably 3 Hour.

In a preferred embodiment of the invention, the preparation method of the fluorine nitrogen type amination reagent shown in formula I exists Gas (such as nitrogen or inert gas) protection is lower to be carried out.

In the preparation method of the fluorine nitrogen type amination reagent shown in formula I, after the fluorination reaction, may be used also Further include the operation of post-processing.The method of the post-processing can be the method for organic synthesis field post-processing routine.This Invention preferably includes the following steps: the reaction solution after fluorination reaction at room temperature, is separated by solid-liquid separation (preferably through one Segment short column of silica gel is separated by solid-liquid separation, and elutes the short column of silica gel with halogenated alkanes solvents), it removes organic molten in filtrate Agent (is preferably concentrated under reduced pressure), separates through rapid column chromatography (petrol ether/ethyl acetate=20:1).

R³And R⁴In, the substituted C₆-C₃₀Aryl and the substituted C₂-C₃₀Substituent group is preferably only in heteroaryl On the spot selected from nitro,Methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl are (and its different Structure body), n-hexyl (and its isomers), chloromethyl, trifluoromethyl, phenyl, naphthalene, anthryl, phenanthryl, F, Cl, Br, I,With one or more of cyano (such as 1-6, preferably 1-3, more preferable 1-2)；Wherein, R⁵For (or its is different for methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl (or its isomers), n-hexyl Structure body),Trifluoromethyl orR⁷It independently is methyl, ethyl, n-propyl, isopropyl, normal-butyl, tertiary fourth Base, isobutyl group, n-pentyl (or its isomers), n-hexyl (or its isomers) orWhen substituent group is When multiple, the substitution is identical or different.

R³And R⁴In, the substituted or unsubstituted C₆-C₃₀The preferably substituted or unsubstituted C of aryl₆-C₁₄Aryl.It is described Substituted or unsubstituted C₆-C₁₄The preferably substituted or unsubstituted phenyl of aryl, substituted or unsubstituted naphthalene, substitution do not take The anthryl in generation, or, substituted or unsubstituted phenanthryl.

R³And R⁴In, the C substituted or unsubstituted₂-C₃₀C in heteroaryl₂-C₃₀The preferred C of heteroaryl₂-C₁₂Heteroaryl (such as C₄-C₁₂Heteroaryl).The C₂-C₁₂The preferred pyridyl group of heteroaryl, thienyl, acridine, carbazole, cinnolines, carboline, Quinoxaline, imidazoles, pyrazoles, pyrroles, indoles, indoline, benzotriazole, benzimidazole, furans, thiophene, isothiazole, benzo thiophene Pheno, dihydrobenzo thiophene, benzofuran, isobenzofuran, benzoxazoles, benzofuraxan, benzopyrazoles, quinoline, benzazine, It is isoquinolin, oxazole, oxadiazoles, isoxazole, indoles, pyrazine, pyridopyridine, tetrazolo pyridine, pyridazine, pyridine, naphthalene pyrimidine, phonetic Pyridine, pyrroles, tetrazolium, thiadiazoles, thiazole, thiophene, triazole, quinazoline, tetrahydroquinoline, dihydrobenzo imidazoles, Dihydrobenzofuranes, Dihydrobenzo oxazole or dihydroquinoline.

R³And R⁴In, the C substituted or unsubstituted₂-C₃₀In heteroaryl, when hetero atom is N and the N atom is sp3 hydridization When, N it is upper can connect substituent, the substituent group is preferably C₁-C₁₀Alkyl, C₆-C₁₄Aryl, halogen, More preferably(such as Boc (tertbutyloxycarbonyl) or Ac (acetyl group)).

R³And R⁴In, the C substituted or unsubstituted₂-C₃₀The more preferably substituted or unsubstituted following groups of heteroaryl:Wherein X is N, O, S, NBoc or NAc.

In a preferred embodiment of the invention, R³And R⁴It independently is phenylNaphthalene (such as ), phenanthryl (such as)、

R^3a、R^3b、R^3c、R^3d、R^4a、R^5a、R^4b、R^5b、R^6a、R^6b、R^6cAnd R⁸In, the C₁-C₁₀The preferred C of alkyl₁-C₆Alkane Base.The C₁-C₆The preferred methyl of alkyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl, just oneself Base and their various isomers.The C₆-C₃₀The C that aryl replaces₁-C₁₀The preferred C of alkyl₆-C₁₄The C that aryl replaces₁-C₆Alkane Base.The C₆-C₁₄The C that aryl replaces₁-C₆The preferred benzyl of alkyl.

Work as R^4aAnd R^5a、R^4bAnd R^5bCoupled carbon atom is formed together C₃-C₁₀When naphthenic base, the C₃-C₁₀Cycloalkanes The preferred C of base₃-C₇Naphthenic base.The C₃-C₇The preferred cyclopropyl of naphthenic base, cyclobutyl, cyclopenta, cyclohexyl or suberyl.

R^6a、R^6bAnd R^6cIn, the halogen preferred F, Cl, Br or I.

R^a1、R^a2、R^a3、R^a4And R^a5In, the halogen preferred F, Cl, Br or I.

R^a1、R^a2、R^a3、R^a4、R^a5、R⁹And R^2’In, the C₁-C₁₀The preferred C of alkyl₁-C₆Alkyl.The C₁-C₆Alkyl It is preferred that methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl, n-hexyl or theirs is various different Structure body.

In the present invention, term " heteroaryl " indicates the stabilization monocycle or two rings that may be up to 7 atoms in each ring, wherein extremely A few ring is aromatic rings and is selected from the hetero atom of O, N and S containing 1-4.Such asIn the definition of heteroaryl In range.

In the present invention, term " aryl " refers to any stable monocycle or bicyclic that may be up to 7 atoms in each ring Carbocyclic ring, wherein at least one ring are aromatic rings.Such asAryl as defined in the range of.

Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can any combination to get the present invention it is each preferably Example.

The reagents and materials used in the present invention are commercially available.

In the present invention, room temperature refers to 10-40 DEG C.

The positive effect of the present invention is that:

Fluorine nitrogen type amination reagent of the invention is under catalyst and ligand effect, using alkene as substrate, not by alkene Symmetrical amine arylation reaction, with good yield, outstanding corresponding selection obtains optically active 2,2- diaryl ethylamine Compound.

Specific embodiment

The present invention is further illustrated below by the mode of embodiment, but does not therefore limit the present invention to the reality It applies among a range.In the following examples, the experimental methods for specific conditions are not specified, according to conventional methods and conditions, or according to quotient The selection of product specification.

In following embodiments, concrete operations temperature is not limited, is each meant and is carried out under the conditions of room temperature (10-40 DEG C).

Embodiment 1

In 500mL three-necked bottle, N- methyl benzenesulfonamide (13.5g, 78.9mmol) is dissolved in FCCl₃/HCCl₃(200mL, V/v 1:1) in the mixed solvent, after being cooled to -78 DEG C, F₂/N₂(2:8) gas slowly be passed into reaction solution (1-2 bubble/point Clock).After reaction 3 hours, TLC shows that raw material has consumed most.It is passed through N₂After half an hour, after reacting recovery room temperature, by reaction solution Cross a bit of short column of silica gel, CH₂Cl₂Elution, after filtrate is concentrated, rapid column chromatography separates (petrol ether/ethyl acetate=20:1) and obtains To colourless liquid 6.7g (45%yield).R_f=0.5 (petrol ether/ethyl acetate=10:1)¹H NMR(400MHz,CDCl₃)δ 7.97 (d, J=8.0Hz, 2H), 7.77 (t, J=8.0Hz, 1H), 7.64 (t, J=8.0Hz, 2H), 3.17 (d, J=31.6Hz, 3H).¹³C NMR(100MHz,CDCl₃) δ 135.0,131.0,130.1,129.3,40.8 (d, J=12.2Hz)¹⁹F NMR (376MHz,CDCl₃) δ -37.46 (q, J=31.6Hz) .HRMS:m/z (ESI) calculated value [M+H]⁺: 190.0333, measured value: 190.0332.IR ν_max/cm^-1 1449,1368,1181,1087,1029,1000,861,731,686,652,622,578, 552,528,484.

Embodiment 2

It is weighed into NaH (3.6g, 60mmol, 60wt%in mineral oil), is added anhydrous in 500mL round-bottomed bottle CH₂Cl₂(250mL), stirs into paste.Under Ar gas shielded, it is added dropwise to the dichloromethane solution of N- alkyl benzene sulfonamide (30mmol) (50mL) has bulk gas generation during being added dropwise.After being added dropwise, continue stirring 30 minutes at room temperature.The double benzene sulphurs of N- fluoro Acid imide (NFSI, 56g, 180mmol) is added in reaction system, is stirred 6 hours at room temperature.Reaction solution is slowly poured into ice Unreacted NaH is quenched in water.Separatory funnel separates organic phase, water phase CH₂Cl₂(200mL × 3) extraction, anhydrous MgSO₄It is dry Dry organic phase, filtering.After filtrate concentration, rapid column chromatography separation (PE/EA=20:1) obtains target product.

The reaction of N- cumene sulfonamide (6.0g, 30mmol) obtains red liquid 3.36g, 52%yield.R_f= 0.7 (PE/EA=10:1)¹H NMR(400MHz,CDCl₃) δ 7.98 (d, J=7.6Hz, 2H), 7.71 (t, J=8.0Hz, 1H), 7.59 (t, J=8.0Hz, 2H), 4.25-4.01 (m, 1H), 1.33 (d, J=6.4Hz, 6H)¹³C NMR(100MHz,CDCl₃)δ 135.2,134.5,129.3 (d, J=1.2Hz), 129.2,55.4 (d, J=13.9Hz), 19.3 (d, J=6.1Hz)¹⁹F NMR (376MHz,CDCl₃) δ -76.08 (d, J=34.6Hz) .HRMS:m/z (ESI) calculated [M+H]⁺:218.0646, measured:218.0646.IR ν_max/cm^-1 2987,2943,1585,1449,1356,1171,1086,892,756,727, 685,653,606,573,552.

The reaction of N- ethyl beneznesulfonamide (13.5g, 72.9mmol) obtains yellow liquid 6.7g, 45%yield.R_f= 0.7 (PE/EA=10:1)¹H NMR(400MHz,CDCl₃) δ 7.96 (d, J=8.0Hz, 2H), 7.75 (t, J=7.6Hz, 1H), 7.63 (t, J=7.6Hz, 2H), 3.31 (dq, J=39.6,7.6Hz, 2H), 1.34 (t, J=7.2Hz, 3H)¹³C NMR (100MHz,CDCl₃) δ 134.9,131.9,129.9,129.2,48.8 (d, J=12.9Hz), 11.6.¹⁹F NMR(376MHz, CDCl₃) δ -52.90 (t, J=39.6Hz) .HRMS:m/z (ESI) calculated [M+H]⁺:204.0489,measured: 204.0489.IR ν_max/cm^-1 2991,1584,1370,1178,1087,1039,935,893,757,731,685,575, 557.

The reaction of N- ethyl para toluene sulfonamide (6.0g, 30mmol) obtains red solid 3.1g, 48%yield.R_f= 0.7 (PE/EA=10:1)¹H NMR(400MHz,CDCl₃) δ 7.82 (d, J=8.4Hz, 2H), 7.41 (d, J=8.4Hz, 2H), 3.28 (dq, J=39.6,7.2Hz, 2H), 2.48 (s, 3H), 1.32 (t, J=7.2Hz, 3H)¹³C NMR(100MHz,CDCl₃) δ 146.2,130.0,129.9,128.7,48.9 (d, J=12.8Hz), 21.7,11.6.¹⁹F NMR(376MHz,CDCl₃)δ- 52.87 (t, J=39.8Hz) .HRMS:m/z (ESI) calculated [M+H]⁺:218.0646,measured: 218.0645.IR ν_max/cm^-1 2993,1592,1364,1170,1087,1037,937,889,704,638,565,541, 477.

According to 2 same procedure of embodiment, corresponding reaction raw materials are replaced, synthesize following compounds:

The reaction of N- ethyl para toluene sulfonamide (6.0g, 30mmol) obtains weak yellow liquid 4.35g, 63%yield) .R_f=0.7 (PE/EA=10:1)¹H NMR(400MHz,CDCl₃) δ 7.99 (d, J=7.6Hz, 2H), 7.67 (t, J= 7.6Hz, 1H), 7.56 (t, J=7.6Hz, 2H), 1.47 (d, J=2.0Hz, 9H)¹³C NMR(100MHz,CDCl₃)δ137.3, 134.2,129.0 (d, J=1.6Hz), 128.9,66.6 (d, J=11.4Hz), 27.2 (d, J=6.0Hz)¹⁹F NMR (376MHz,CDCl₃)δ-62.47(s).HRMS:m/z(ESI)calculated[M+H]⁺:232.0802,measured: 232.0802.IR ν_max/cm^-1 2986,2939,1478,1449,1402,1351,1166,1089,894,795,755,721, 685,627,584,554.

N- ethyl obtains yellow liquid 1.35g to the reaction of trifluoromethyl benzene sulfonamide (5.06g, 20mmol), and 25% yield.R_f=0.8 (PE/EA=8:1)¹H NMR(400MHz,CDCl₃) δ 8.10 (d, J=8.4Hz, 2H), 7.89 (d, J= 8.4Hz, 2H), 3.36 (dq, J=39.6,7.2Hz, 2H), 1.36 (t, J=7.2Hz, 3H)¹³C NMR(100MHz,CDCl₃)δ 136.3 (q, J=33.0Hz), 135.8,130.5 (d, J=1.5Hz), 126.4 (q, J=3.4Hz), 122.9 (q, J= 271.8Hz), 48.7 (d, J=12.6Hz), 11.5.¹⁹F NMR(376MHz,CDCl₃) δ -52.82 (t, J=39.6Hz), - 63.44(s).HRMS:m/z(ESI)calculated[M+H]⁺:272.0363,measured:273.0362.IR ν_max/cm^-1 1404,1380,1319,1174,1132,1107,1060,1006,900,843,790,719,680,588,553,426.

N- ethyl obtains red solid 2.5g to the reaction of methoxybenzenesulphoismide (6.46g, 30mmol), and 36% yield.R_f=0.4 (PE/EA=8:1)¹H NMR(400MHz,CDCl₃) δ 7.87 (d, J=8.8Hz, 2H), 7.07 (d, J= 8.8Hz, 2H), 3.91 (s, 3H), 3.28 (dq, J=40.0,7.2Hz, 1H), 1.32 (t, J=7.2Hz, 3H)¹³C NMR (100MHz,CDCl₃) δ 164.7,132.2,122.9,114.5,55.8,48.8 (d, J=12.9Hz), 11.6.¹⁹F NMR (376MHz,CDCl₃) δ -52.63 (t, J=40.0Hz) .HRMS:m/z (ESI) calculated [M+H]⁺:234.0595, measured:234.0594.IR ν_max/cm^-1 2989,2921,2848,1591,1365,1267,1217,1187,1092, 1023,884,831,803,703,551.

Embodiment 3

Step 1: in 100mL tube sealing, ligand L * (82.0mg, 0.20mmol) and Cu (CH₃CN)₄PF₆(37.0mg, 0.10mmol) under protection of argon gas, it is dissolved in DMA/CH₂Cl₂In (1:4,20mL), after stirring 0.5 hour, what is obtained is colourless molten Liquid is stand-by.

Step 2: in 10mL tube sealing, being added as formula III compound represented (0.40mmol, 2.0equiv) and anhydrous LiOtBu(8.0mg,0.10mmol,0.5equiv).Under protection of argon gas, it in being cooled to -20 DEG C of reaction tubes, sequentially adds Copper catalyst solution (2.0mL) is stated, such as Formula II compound represented (0.20mmol, 1.0equiv), fluorine nitrogen type shown in formula I Amination reagent (0.4mmol, 2.0equiv), reaction solution become blue.Reaction stirred at -10 DEG C, at the appointed time after, instead It answers liquid 20mL ethyl acetate to dilute, washes (10mL × 3).Organic phase is through anhydrous MgSO₄It dries, filters, after concentrating filter liquor, Rapid column chromatography separation (petrol ether/ethyl acetate, according to both specific TLC situation selections of compound ratio) obtains target and produces Object, ee value are split by chiral column by HPLC and are measured.

Wherein, the structure of fluorine nitrogen type amination reagent shown in formula I is

Compound P1

After reaction 5 days, colourless thick liquid 65.2mg (81%yield, 92%ee), R are obtained_f=0.4 (PE/EA=5: 1).¹H NMR(400MHz,CDCl₃)δ8.11–8.02(m,1H),7.87–7.81(m,1H),7.80–7.70(m,3H),7.59– 7.40 (m, 7H), 7.37-7.20 (m, 5H), 5.12 (t, J=8.0Hz, 1H), 3.92 (dd, J=13.6,7.6Hz, 1H), 3.57 (dd, J=13.6,8.4Hz, 1H), 2.59 (s, 3H)¹³C NMR(100MHz,CDCl₃)δ141.6,137.3,136.6, 134.0,132.5,131.6,129.0,128.9,128.6,128.4,127.6,127.3,126.8,126.2,125.5, 125.3,125.0,123.3,54.8,45.0,35.6.HRMS:m/z (ESI) calculated (calculated value) [M+H]⁺: 402.1522, measured (measured values): 405.1524.IR ν_max/cm^-1 2962,1446,1335,1260,1161,1088, 1025,796,745,695,577.^[α] _D ^27.4 45.02(c 1.07,CHCl₃) .HPLC (and AD-H, 0.46*25cm, 5 μm, just oneself Alkane/isopropanol=7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time=8.95min (a large amount of) and 11.53min (a small amount of)

Compound P2

After reaction 5.5 days, faint yellow thick liquid 76.8mg (80%yield, 92%ee), R are obtained_f=0.5 (PE/EA =5:1)¹H NMR(400MHz,CDCl₃) δ 8.28 (dd, J=8.8,1.6Hz, 1H), 8.08 (d, J=8.0Hz, 1H), 7.81 (d, J=7.6Hz, 1H), 7.77-7.69 (m, 2H), 7.62-7.41 (m, 6H), 7.32-7.18 (m, 5H), 5.08 (t, J= 8.4Hz, 1H), 3.96 (dd, J=13.2,8.0Hz, 1H), 3.46 (dd, J=13.6,8.0Hz, 1H), 2.59 (s, 3H) .¹³CNMR(100MHz,CDCl₃)δ141.1,137.1,136.5,133.0,132.6,132.3,129.4,129.1,128.7, 128.3,128.1,127.3,127.0,127.0,126.9,125.6,123.7,122.3,54.7,44.9,35.7.HRMS:m/z (ESI)calculated[M+H]⁺:480.0627,measured:480.0631.IR ν_max/cm^-1 2962,1259,1015, 796,694,576.^[α] _D ^27.6 59.16(c 0.83,CHCl₃) .HPLC (AD-H, 0.46*25cm, 5 μm, n-hexane/isopropanol= 7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time=9.11min (a small amount of) and 9.97min (a large amount of)

Compound P3

After reaction 5.5 days, faint yellow thick liquid 46.9mg (47%yield, 90%ee), R are obtained_f=0.5 (PE/EA =4:1)¹H NMR(400MHz,CDCl₃)δ8.35–8.29(m,1H),8.06–7.99(m,1H),7.77–7.70(m,2H), 7.60-7.45 (m, 6H), 7.33-7.26 (m, 4H), 7.25-7.17 (m, 1H), 6.84 (d, J=8.0Hz, 1H), 5.03 (t, J =8.0Hz, 1H), 4.53 (q, J=8.0Hz, 2H), 3.99 (dd, J=13.2,8.0Hz, 1H), 3.45 (dd, J=13.2, 8.0Hz,1H),2.61(s,3H).¹³C NMR(100MHz,CDCl₃)δ152.3,141.6,137.1,132.7,132.6, 130.3,129.1,128.7,128.3,127.3,127.2,126.9,125.8,125.5,12 4.8,123.4 (q, J= 276.3Hz), 123.1,122.5,104.8,65.9 (q, J=35.6Hz), 54.7,44.5,35.4.¹⁹F NMR(376MHz, CDCl₃) δ -73.71 (t, J=8.0Hz) .HRMS:m/z (ESI) calculated [M+NH₄]⁺:517.1767,measured: 517.1775.IR ν_max/cm^-1 2960,1636,1260,1155,1088,1020,797,744,695,668,666,576.^[α] _D ^27.8 51.67(c0.78,CHCl₃) .HPLC (IG, 0.46*25cm, 5 μm, n-hexane/isopropanol=8/2, flow velocity 0.7mL/ Min, detection range wavelength 214nm) retention time=16.81min (a large amount of) and 18.28min (a small amount of)

Compound P4

After reaction 5.5 days, faint yellow thick liquid 68.9mg (75%yield, 89%ee), R are obtained_f=0.3 (PE/EA =10:3)¹H NMR(400MHz,CDCl₃) δ 7.79 (d, J=8.8Hz, 1H), 7.76-7.66 (m, 4H), 7.54-7.35 (m, 5H), 7.31-7.26 (m, 4H), 7.23-7.19 (m, 2H), 4.44 (t, J=8.0Hz, 1H), 3.78 (dd, J=13.2, 8.4Hz, 1H), 3.67 (dd, J=13.2,8.4Hz, 1H), 2.58 (s, 3H), 2.33 (s, 3H)¹³C NMR(100MHz, CDCl₃)δ169.6,148.2,141.2,138.8,137.3,132.6,132.5,131.4,129.3,129.0,128.6, 128.2,128.0,127.3,127.2,126.9,126.5,121.4,118.2,54.4,49.9,35.4,21.1.HRMS:m/z (ESI)calculated[M+H]⁺:460.1577,measured:460.1579.IR ν_max/cm^-1 1750,1507,1473, 1446,1334,1197,1161,744,696,577.^[α] _D ^28.2 11.74(c 1.07,CHCl₃).HPLC(AD-H,0.46* 25cm, 5 μm, n-hexane/isopropanol=7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time= 23.46min (a small amount of) and 26.78min (a large amount of)

Compound P5

After reaction 3 days, faint yellow thick liquid 62.8mg (77%yield, 84%ee), R are obtained_f=0.5 (PE/EA= 8:1).¹H NMR(400MHz,CDCl₃) δ 7.74-7.66 (m, 2H), 7.55 (t, J=6.8Hz, 1H), 7.46 (t, J=7.6Hz, 2H), 7.34-7.26 (m, 6H), 7.26-7.16 (m, 3H), 4.24 (t, J=8.0Hz, 1H), 3.74-3.54 (m, 2H), 2.56 (s,3H),1.28(s,9H).¹³C NMR(100MHz,CDCl₃)δ149.5,141.6,138.4,137.5,132.5,129.0, 128.6,128.2,127.7,127.4,126.7,125.5,54.6,49.6,35.3,34.4,31.3.HRMS:m/z(ESI) calculated[M+H]⁺:408.1992,measured:408.1993.IR ν_max/cm^-1 2960,1446,1337,1260, 1163,1089,936,739,690,577.^[α] _D ^28.8 2.85(c 0.79,CHCl₃) .HPLC (AD-H, 0.46*25cm, 5 μm, just Hexane/isopropyl alcohol=96/4, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time=15.95min (a small amount of) and 22.80min (a large amount of)

Compound P6

After reaction 3 days, faint yellow thick liquid 59.0mg (72%yield, 83%ee) after 3days, R are obtained_f= 0.4 (PE/EA=3:1)¹H NMR(400MHz,CDCl₃)δ7.74–7.68(m,2H),7.60–7.52(m,1H),7.51–7.44 (m, 2H), 7.33-7.19 (m, 7H), 7.05-6.99 (m, 2H), 4.29 (t, J=8.0Hz, 1H), 3.60 (d, J=8.0Hz, 2H),2.56(s,3H),2.27(s,3H).¹³C NMR(100MHz,CDCl₃)δ169.4,149.3,141.0,138.9,137.2, 132.5,129.1,129.0,128.6,128.1,127.3,126.9,121.6,54.6,49.4,35.3,21.1.HRMS:m/z (ESI)calculated[M+H]⁺:410.1421,measured:410.1422.IR ν_max/cm^-1 2922,1760,1506, 1446,1337,1197,1163,1089,1017,747,696,577.^[α] _D ^28.9-0.75(c 1.02,CHCl₃).HPLC(IC, 0.46*25cm, 5 μm, n-hexane/isopropanol=6/4, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time= 28.91min (a small amount of) and 31.29min (a large amount of)

Compound P7

After reaction 7.5 days, faint yellow thick liquid 45.0mg (63%yield, 88%ee), R are obtained_f=0.5 (PE/EA =5:1)¹H NMR(400MHz,CDCl₃) δ 7.71 (d, J=8.0Hz, 2H), 7.58 (t, J=7.2Hz, 1H), 7.49 (t, J= 7.6Hz, 2H), 7.35-7.18 (m, 9H), 4.26 (t, J=8.0Hz, 1H), 3.68 (dd, J=13.6,8.8Hz, 1H), 3.51 (dd, J=13.6,7.6Hz, 1H), 2.58 (s, 3H)¹³C NMR(100MHz,CDCl₃)δ141.0,139.8,137.2, 132.6,129.6,129.1,128.7,128.0,127.3,127.0,54.5,49.3,35.3.HRMS:m/z(ESI) calculated[M+H]⁺:386.0976,measured:386.0977.I_{R νmax}/cm^-12922,1490,1446,1337, 1260,1162,1089,1004,935,743,690,577,553.^[α] _D ^27.9 5.85(c 0.84,CHCl₃).HPLC(AD-H, 0.46*25cm, 5 μm, n-hexane/isopropanol=9/1, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time= 20.23min (a small amount of) and 21.89min (a large amount of)

Compound P8

After reaction 7.5 days, colourless thick liquid 62.0mg (74%yield, 87%ee), R are obtained_f=0.4 (PE/EA= 5:1).¹H NMR(400MHz,CDCl₃)δ7.75–7.67(m,2H),7.60–7.53(m,3H),7.52–7.45(m,2H),7.42 (d, J=8.0Hz, 2H), 7.33-7.30 (m, 2H), 7.26-7.22 (m, 3H), 4.36 (t, J=8.0Hz, 1H), 3.77 (dd, J =13.6,8.8Hz, 1H), 3.52 (dd, J=13.6,7.6Hz, 1H), 2.59 (s, 3H)¹³C NMR(100MHz,CDCl₃)δ 145.4,140.6,137.1,132.7,129.1,128.8,128.6,128.1,127.3,12 7.2,125.5 (q, J= 3.7Hz), 124.1 (q, J=270.3Hz), 54.3,49.8,35.4.¹⁹F NMR(376MHz,CDCl₃)δ-62.43(s) .HRMS:m/z(ESI)calculated[M+H]⁺:420.1240,measured:420.1243.IR ν_max/cm^-11447, 1323,1161,1188,1068,1018,936,831,746,691,577,550.^[α] _D ^29.09.14(c 1.19,CHCl₃).HPLC When (AD-H, 0.46*25cm, 5 μm, n-hexane/isopropanol=7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) retains Between=7.69min (a small amount of) and 8.20min (a large amount of)

Compound P9

After reaction 4 days, yellow thick liquid 53.2mg (65%yield, 90%ee), R are obtained_f=0.3 (PE/EA=7: 2).¹H NMR(400MHz,CDCl₃) δ 7.98 (d, J=8.0Hz, 2H), 7.74-7.67 (m, 2H), 7.57 (t, J=7.2Hz, 1H), 7.49 (t, J=7.2Hz, 2H), 7.37 (d, J=8.4Hz, 2H), 7.34-7.28 (m, 2H), 7.27-7.19 (m, 3H), 4.35 (t, J=8.0Hz, 1H), 3.89 (s, 3H), 3.72 (dd, J=13.6,8.4Hz, 1H), 3.57 (dd, J=13.6, 7.6Hz, 1H), 2.57 (s, 3H)¹³C NMR(100MHz,CDCl₃)δ166.8,146.6,140.7,137.2,132.6, 129.9,129.1,128.8,128.7,128.3,128.1,127.3,127.1,54.4,52.1,50.0,35.5.HRMS:m/z (ESI)calculated[M+H]⁺:410.1421,measured:410.1423.IR ν_max/cm^-1 1761,1446,1339, 1279,1162,1112,937,742,691,577,554.^[α] _D ^29.1 9.60(c 1.33,CHCl₃).HPLC(AD-H,0.46* 25cm, 5 μm, n-hexane/isopropanol=7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time= 15.76min (a small amount of) and 16.89min (a large amount of)

Compound P10

After reaction 5.5 days, colourless thick liquid 66.6mg (78%yield, 90%ee), R are obtained_f=0.5 (PE/EA= 5:1).¹H NMR(400MHz,CDCl₃) δ 7.71 (d, J=8.0Hz, 2H), 7.58-7.50 (m, 5H), 7.48-7.39 (m, 4H), 7.36-7.30 (m, 7H), 7.25-7.20 (m, 1H), 4.32 (t, J=8.0Hz, 1H), 3.67 (m, 2H), 2.59 (s, 3H)¹³C NMR(100MHz,CDCl₃)δ141.4,140.6,140.5,139.6,137.4,132.5,129.0,128.7,128.7, 128.6,128.2,127.3,127.3,127.2,126.9,126.9,54.5,49.7,35.3.HRMS:m/z(ESI) calculated[M+H]⁺:428.1679,measured:428.1686.IR ν_max/cm^-1 2922,1558,1473,1338, 1260,1162,1088,936,798,745,634,577.^[α] _D ^28.9 2.69(c 0.73,CHCl₃).HPLC(IE-3,0.46* 25cm, 5 μm, n-hexane/isopropanol=9/1, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time= 50.50min (a large amount of) and 55.87min (a small amount of)

Compound P11

After reaction 5.5 days, yellow solid 49.2mg (53%yield, 91%ee), R are obtained_f=0.6 (PE/EA=5:1) .¹HNMR(400MHz,CDCl₃) δ 7.72 (d, J=7.6Hz, 2H), 7.54 (m, 4H), 7.37-7.17 (m, 7H), 4.77 (t, J= 8.0Hz, 1H), 3.67 (dd, J=13.2,8.0Hz, 1H), 3.49 (dd, J=13.2,8.0Hz, 1H), 2.65 (s, 3H)¹³C NMR(100MHz,CDCl₃)δ140.7,139.1,137.0,133.1,132.7,132.1,131.2,131.2,129.1, 128.2,128.5,127.4,127.3,120.9,53.2,45.0,34.8.HRMS:m/z(ESI)calculated[M+H]⁺: 464.0081,measured:464.0085.IR ν_max/cm^-1 2922,1260,1018,797.^[α] _D ^28.7 38.84(c 0.96, CHCl₃) .HPLC (AD-H, 0.46*25cm, 5 μm, n-hexane/isopropanol=94/6, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time=16.67min (a small amount of) and 20.76min (a large amount of)

Compound P12

After reaction 7.5 days, faint yellow thick liquid 68.6mg (70%yield, 92%ee), R are obtained_f=0.5 (PE/EA =10:3)¹H NMR(400MHz,CDCl₃) δ 7.71 (d, J=7.6Hz, 2H), 7.57 (t, J=7.6Hz, 1H), 7.49 (t, J =7.6Hz, 2H), 7.34-7.19 (m, 5H), 7.09 (s, 1H), 6.99 (s, 1H), 4.68 (dd, J=10.0,7.2Hz, 1H), 3.93 (s, 3H), 3.92-3.86 (m, 1H), 3.85 (s, 3H), 3.22 (dd, J=13.2,6.8Hz, 1H), 2.68 (s, 3H)¹³C NMR(100MHz,CDCl₃)δ148.6,148.3,140.2,136.9,132.6,131.3,129.0,128.6,128.3, 127.3,126.9,115.5,114.8,112.2,56.2,56.0,53.2,46.8,34.1.HRMS:m/z(ESI) calculated[M+H]⁺:490.0682,measured:490.0692.IR ν_max/cm^-1 1540,1504,1457,1260, 1209,1161,1089,1027,942,744,694,603,577.^[α] _D ^28.7 32.81(c 0.93,CHCl₃).HPLC(AD-H, 0.46*25cm, 5 μm, n-hexane/isopropanol=7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time= 12.90min (a large amount of) and 16.49min (a small amount of)

Compound P14

After reaction 7.5 days, white solid 60.8mg (47%yield, 87%ee), R are obtained_f=0.5 (PE/EA=5:3) .¹HNMR(400MHz,CDCl₃) δ 8.14 (d, J=8.0Hz, 2H), 7.73 (d, J=8.0Hz, 2H), 7.64-7.48 (m, 3H), 7.44 (d, J=8.0Hz, 2H), 7.39-7.19 (m, 6H), 7.00-6.86 (m, 2H), 4.39 (t, J=8.0Hz, 1H), 3.78 (dd, J=13.6,8.8Hz, 1H), 3.55 (dd, J=13.6,7.6Hz, 1H), 2.94-2.93 (m, 2H), 2.60 (s, 3H), 2.59–1.93(m,8H),1.68–1.39(m,5H),0.92(s,3H).¹³C NMR(100MHz,CDCl₃)δ220.9,165.1, 148.7,147.3,140.6,138.0,137.3,137.1,132.6,130.4,129.1,128.8,128.5,128.1, 128.0,127.3,127.1,126.4,121.6,118.8,54.3,50.3,50.0,47.9,44.1,37.9,35.8,35.4, 31.5,29.4,26.3,25.7,21.5,13.8.HRMS:m/z(ESI)calculated[M+H]⁺:648.2778, measured:648.2800.IRν_max/cm^-1 2925,1731,1493,1340,1262,1163,1072,746,691,578, 554.^[α] _D ^28.8 51.70(c 0.59,CHCl₃) .HPLC (AD-H, 0.46*25cm, 5 μm, n-hexane/isopropanol=5/5, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time=46.83min (a small amount of) and 52.73min (a large amount of)

Compound P15

After reaction 3 days, colourless thick liquid 41.2mg (42%yield, 84%ee), R are obtained_f=0.5 (PE/EA=3: 1).¹H NMR(400MHz,CDCl₃) δ 8.03 (d, J=8.0Hz, 1H), 7.71 (d, J=7.2Hz, 2H), 7.62-7.51 (m, 2H), 7.51-7.40 (m, 3H), 7.30 (d, J=4.3Hz, 4H), 7.24-7.18 (m, 2H), 6.51 (d, J=3.6Hz, 1H), 4.38 (t, J=8.0Hz, 1H), 3.68 (m, 2H), 2.58 (s, 3H), 1.65 (s, 9H)¹³C NMR(100MHz,CDCl₃)δ 149.7,141.9,137.5,135.9,132.5,130.8,129.0,128.6,128.2,127.3,126.7,126.3, 124.5,120.3,115.2,107.3,83.7,54.9,49.8,35.4,28.1.HRMS:m/z(ESI)calculated[M+H ]⁺:491.1999,measured:491.2000.IR ν_max/cm^-1 2962,1729,1469,1332,1258,1160,1083, 1022,746,698,576,544.^[α] _D ^29.0 1.55(c 1.02,CHCl₃) .HPLC (AD-H, 0.46*25cm, 5 μm, n-hexane/ Isopropanol=7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time=10.00min (a small amount of) and 11.95min (a large amount of)

Compound P16

After reaction 5.5 days, colourless thick liquid 37.1mg (43%yield, 91%ee), R are obtained_f=0.5 (PE/EA= 10:3).¹H NMR(400MHz,CDCl₃)δ8.09–8.05(m,1H),7.84–7.80(m,1H),7.77–7.68(m,3H), 7.57-7.38 (m, 7H), 7.27-7.18 (m, 2H), 6.85-6.76 (m, 2H), 5.06 (t, J=8.0Hz, 1H), 3.88 (dd, J =13.2,7.2Hz, 1H), 3.73 (s, 3H), 3.52 (dd, J=13.2,8.0Hz, 1H), 2.59 (s, 3H)¹³C NMR (100MHz,CDCl₃)δ158.3,137.3,136.9,134.0,133.6,132.5,131.6,129.4,129.0,128.9, 127.5,127.3,126.2,125.4,125.3,124.8,123.3,114.0,55.1,54.9,44.1,35.6.HRMS:m/z (ESI)calculated[M+H]⁺:432.1628,measured:432.1632.IR ν_max/cm^-1 2961,2917,2850, 1512,1443,1334,1252,1157,1086,1025,934,799,746,693,578,549.^[α] _D ^28.7 30.89(c 0.70,CHCl₃) .HPLC (AD-H, 0.46*25cm, 5 μm, n-hexane/isopropanol=8/2, flow velocity 0.7mL/min, detection range Wavelength 214nm) retention time=15.37min (a large amount of) and 20.47min (a small amount of)

Compound P17

After reaction 5.5 days, yellow thick liquid 54.5mg (65%yield, 92%ee), R are obtained_f=0.4 (PE/EA= 5:1).¹H NMR(400MHz,CDCl₃)δ8.04–8.02(m,1H),7.88–7.81(m,1H),7.79–7.69(m,3H), 7.57-7.39 (m, 7H), 7.35-7.25 (m, 2H), 7.01-6.91 (m, 2H), 5.17-5.06 (m, 1H), 3.82 (dd, J= 13.6,7.2Hz, 1H), 3.59 (dd, J=13.6,8.8Hz, 1H), 2.60 (s, 3H)¹³C NMR(100MHz,CDCl₃)δ 161.6 (d, J=243.6Hz), 137.2 (d, J=3.0Hz), 137.2,136.5,134.1,132.6,131.5,129.9 (d, J =8.4Hz), 129.1,129.0,127.7,127.3,126.3,125.6,125.3,124.8,123.1,11 5.5 (d, J= 21.3Hz),54.9,44.2,35.7.¹⁹F NMR(375MHz,CDCl₃)δ-115.83(m).HRMS:m/z(ESI) calculated[M+H]⁺:420.1428,measured:420.1432.IR ν_max/cm^-1 2962,1507,1259,1013, 790,758,691,577.^[α] _D ^28.6 44.05(c 0.96,CHCl₃) .HPLC (AD-H, 0.46*25cm, 5 μm, n-hexane/isopropyl Alcohol=7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time=9.41min (a large amount of) and 10.47min be (few Amount)

Compound P18

After reaction 7.5 days, yellow solid 44.4mg (52%yield, 91%ee), R are obtained_f=0.6 (PE/EA=4:1) .¹H NMR(400MHz,CDCl₃)δ8.20–8.07(m,2H),7.79–7.69(m,2H),7.60–7.43(m,6H),7.18– 7.10 (m, 2H), 6.99-6.90 (m, 2H), 5.35 (t, J=8.0Hz, 1H), 3.84 (dd, J=13.6,7.6Hz, 1H), 3.65 (dd, J=13.6,8.4Hz, 1H), 2.60 (s, 3H)¹³C NMR(100MHz,CDCl₃) δ 158.1 (d, J=241.2Hz), (145.1,137.3,132.8 d, J=4.6Hz), 132.7,132.6,129.1,127.4,127.3,126.9,126.0 (d, J= 2.0Hz), 125.5,124.8 (d, J=9.1Hz), 124.4,124.1 (d, J=15.9Hz), 123.1 (d, J=2.9Hz), 121.3 (d, J=6.0Hz), 108.9 (d, J=19.7Hz), 55.8,40.7,36.2.¹⁹F NMR(376MHz,CDCl₃)δ- 123.47(m).HRMS:m/z(ESI)calculated[M+H]⁺:426.0992,measured:426.0999.IR ν_max/cm^-1 2960,2924,1604,1446,1336,1258,1162,739,691,575,541.^[α] _D ^28.4 39.15(c 0.92,CHCl₃) .HPLC (AD-H, 0.46*25cm, 5 μm, n-hexane/isopropanol=7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) Retention time=8.80min (a large amount of) and 9.75min (a small amount of)

Compound P19

After reaction 7.5 days, brownish red thick liquid 68.4mg (72%yield, 90%ee), R are obtained_f=0.6 (PE/EA =4:1)¹H NMR(400MHz,CDCl₃)δ8.16-8.14(m,2H),7.78–7.62(m,4H),7.59–7.48(m,4H), 7.48-7.40 (m, 2H), 7.36-7.10 (m, 4H), 5.40 (t, J=7.6Hz, 1H), 3.88 (dd, J=13.6,7.6Hz, 1H), 3.76 (dd, J=13.6,8.4Hz, 1H), 2.65 (s, 3H)¹³C NMR(100MHz,CDCl₃) δ 158.3 (d, J= 251.3Hz), 146.0,139.6,139.3,137.1,132.8 (d, J=4.5Hz), 132.7,132.0 (d, J=4.6Hz), (129.1,127.5,127.3,126.1 d, J=2.2Hz), 124.9 (d, J=8.3Hz), 124.3,124.2 (d, J= 15.9Hz), 124.0,123.3,123.1 (d, J=3.0Hz), 122.2,122.1,121.4 (d, J=6.0Hz), 108.9 (d, J =19.8Hz), 55.4,41.4,36.2.¹⁹F NMR(376MHz,CDCl₃) δ -123.01 (dd, J=9.5,4.9Hz) .HRMS: m/z(ESI)calculated[M+H]⁺:476.1149,measured:476.1147.IR ν_max/cm^-1 2961,1458, 1396,1334,1159,1015,798,739,689,575.^[α] _D ^28.4-11.50(c 1.08,CHCl₃).HPLC(AD-H,0.46* 25cm, 5 μm, n-hexane/isopropanol=7/3, flow velocity 0.7mL/min, detection range wavelength 214nm) retention time= 11.37min (a large amount of) and 15.18min (a small amount of)

Compound P20

After reaction 7 days, yellow thick liquid 34.5mg (48%yield, 86%ee), R are obtained_f=0.5 (PE/EA=2: 1).¹H NMR(400MHz,CDCl₃) δ 7.72 (d, J=7.2Hz, 2H), 7.60-7.45 (m, 3H), 7.36-7.13 (m, 5H), 6.83 (m, 3H), 4.23 (t, J=8.0Hz, 1H), 3.86 (s, 3H), 3.85 (s, 3H), 3.69 (dd, J=13.6,8.8Hz, 1H), 3.51 (dd, J=13.6,7.6Hz, 1H), 2.59 (s, 3H)¹³C NMR(100MHz,CDCl₃)δ148.9,147.8, 141.8,137.4,133.7,132.5,129.0,128.6,128.0,127.3,126.8,120.1,111.6,111.1,55.9, 55.8,54.6,49.4,35.2.HRMS:m/z(ESI)calculated[M+H]⁺:412.1577,measured:412.1577.^[α] _D ^25.4 16.62(c 0.39,CHCl₃) .HPLC (IC, 0.46*25cm, 5 μm, n-hexane/isopropanol=5/5, flow velocity 0.7mL/ Min, detection range wavelength 214nm) retention time=27.05min (a large amount of) and 29.36min (a small amount of)

Embodiment 4

Under argon atmosphere, be added into 10mL tube sealing optically active 2,2- aryl amine (17.3mg, 0.042mmol, 1.0equiv), Mg powder (48.0mg, 2.0mmol, 47equiv), methanol (1.0mL), after reacting 40min under ultrasound, reaction is mixed Closing object becomes gluey.After TLC adheres to that substrate reactions are complete, after draining reaction dissolvent, diatomite filtering, ethyl acetate/methanol (10:1) elution.After filtrate concentration, rapid column chromatography separates (PE/EA/MeOH/NEt₃=10:10:1:1), obtain light yellow liquid Body 9.5mg (83%yield, 88%ee), R_f=0.4 (PE/EA/MeOH/TEA=10:10:1:1)¹HNMR(400MHz, CDCl₃) δ 7.33-7.17 (m, 5H), 6.79 (m, 3H), 4.19 (t, J=7.6Hz, 1H), 3.85 (s, 3H), 3.84 (s, 3H), 3.20 (d, J=7.6Hz, 2H), 2.45 (s, 3H), 2.33 (br, 1H)¹³C NMR(100MHz,CDCl₃)δ148.9,147.7, 142.8,135.1,128.6,127.8,126.6,119.6,111.5,111.2,56.5,55.8,55.8,50.3, 36.2.HRMS:m/z(ESI)calculated[M+H]⁺:272.1645,measured:272.1644.IR ν_max/cm^-1 2930,2835,2792,1591,1513,1447,1417,1260,1236,1186,1146,1025,753,700,583,540.^[α] _D ^25.8 2.93(c 0.37,CHCl₃) .HPLC (IC, 0.46*25cm, 5 μm, n-hexane/isopropanol/diethylamine=90/10/1, Flow velocity 0.7mL/min, detection range wavelength 214nm) retention time=35.03min (a large amount of) and 44.90min (a small amount of)

Embodiment 5

The reaction property of different substituted nitrogen fluorine amination reagents, reaction condition and the same embodiment of step are listed in table 1 2, difference is, has used different fluorine nitrogen type amination reagents, and for the ease of monitoring, reaction carries out 18 hours at room temperature.Fluorine nitrogen Type amination reagent structure and experimental result are shown in Table 1.

Table 1

Claims (16)

1. a kind of fluorine nitrogen type amination reagent shown in formula I is preparing answering in 2,2- diaryl ethylamine compounds intermediate With, which is characterized in that the application includes the following steps: under gas shield, in organic solvent, matches in copper catalyst and dinitrogen Under the action of body and alkali, by fluorine nitrogen type amination reagent shown in formula I, such as Formula II compound represented and as shown in formula III Compound carries out reaction as follows, and such as formula IV compound represented is made；

Wherein,

R¹For substituted or unsubstituted C₆-C₃₀Aryl；The substituted C₆-C₃₀Substituent group in aryl is selected from halogen, C₁-C₁₀ The C that alkyl, halogen replace₁-C₁₀Alkyl, C₁-C₁₀Alkoxy andOne or more of, R^1’For C₁-C₁₀Alkyl；When When substituent group is multiple, the substituent group is identical or different；The substituted or unsubstituted C₆-C₃₀Aryl is for substitution or not Substituted phenyl；

R²For C₁-C₁₀Straight chained alkyl orWherein, R^1aDefinition and R¹It is identical；

R³And R⁴It independently is substituted or unsubstituted C₆-C₃₀Aryl, or, substituted or unsubstituted C₂-C₃₀Heteroaryl；Described C₂-C₃₀Hetero atom in heteroaryl is selected from one or more of N, O and S；When hetero atom is multiple, the hetero atom phase It is same or different；The substituted C₆-C₃₀Aryl and the substituted C₂-C₃₀Substituent group is independently selected from nitre in heteroaryl Base, C₂-C₆Heteroaryl, C₁-C₁₀The C that alkyl, halogen replace₁-C₁₀Alkyl, C₆-C₁₄Aryl, halogen,With One or more of cyano；Wherein, the C₂-C₆Heteroaryl be that hetero atom is selected from N, O and S, hetero atom number is 1-4 C₂-C₆Heteroaryl；R⁵For C₁-C₁₀The C that alkyl, halogen replace₁-C₁₀Alkyl orR⁶And R⁷It independently is C₁-C₁₀Alkane Base orWhen substituent group is multiple, the substitution is identical or different.

2. application as described in claim 1, which is characterized in that

In fluorine nitrogen type amination reagent shown in formula I, R¹In, the substituted C₆-C₃₀Substituent group in aryl be selected from F, Cl, Br, I, methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl or its isomers, n-hexyl or its Isomers, trifluoromethyl, pentafluoroethyl group, methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy, uncle Butoxy,One or more of；When substituent group be it is multiple when, the substituent group it is identical or It is different；

And/or in fluorine nitrogen type amination reagent shown in formula I, R²In, the C₁-C₁₀Straight chained alkyl is C₁-C₆Straight chained alkyl.

3. application as claimed in claim 2, which is characterized in that

R¹In, the substituted C₆-C₃₀Aryl is

And/or R²In, the C₁-C₆Straight chained alkyl is methyl, ethyl, n-propyl, normal-butyl, n-pentyl or n-hexyl.

4. application according to any one of claims 1 to 3, which is characterized in that

R³And R⁴In, the substituted C₆-C₃₀Aryl and the substituted C₂-C₃₀In heteroaryl substituent group independently selected from Nitro,Methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl or its isomers, just oneself Base or its isomers, chloromethyl, trifluoromethyl, phenyl, naphthalene, anthryl, phenanthryl, F, Cl, Br, I,With One or more of cyano；Wherein, R⁵For methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, positive penta Base or its isomers, n-hexyl or its isomers,Trifluoromethyl orR⁷It independently is methyl, ethyl, just Propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl or its isomers, n-hexyl or its isomers orWhen substituent group is multiple, the substituent group is identical or different；

And/or R³And R⁴In, the substituted or unsubstituted C₆-C₃₀Aryl is substituted or unsubstituted C₆-C₁₄Aryl；

And/or R³And R⁴In, the C substituted or unsubstituted₂-C₃₀C in heteroaryl₂-C₃₀Heteroaryl is C₂-C₁₂Heteroaryl Base；The C substituted or unsubstituted₂-C₃₀In heteroaryl, when hetero atom is N and the N atom is sp3 hydridization, N is upper to be connected Substituent group, the substituent group are C₁-C₁₀Alkyl, C₆-C₁₄Aryl, halogen,

5. application as claimed in claim 4, which is characterized in that R³And R⁴In, the substituted or unsubstituted C₆-C₁₄Aryl For substituted or unsubstituted phenyl, substituted or unsubstituted naphthalene, substituted or unsubstituted anthryl, or, substituted or unsubstituted Phenanthryl；

And/or R³And R⁴In, the C substituted or unsubstituted₂-C₃₀C in heteroaryl₂-C₃₀Heteroaryl is C₄-C₁₂Heteroaryl Base；The C substituted or unsubstituted₂-C₃₀In heteroaryl, when hetero atom is N and the N atom is sp3 hydridization, N is upper to be connected Substituent group, the substituent group are tertbutyloxycarbonyl or acetyl group；The C substituted or unsubstituted₂-C₃₀Heteroaryl be replace or Unsubstituted following groups:Wherein X is N, O, S, NBoc or NAc.

6. application as claimed in claim 5, which is characterized in that R³And R⁴In, the substituted or unsubstituted C₆-C₁₄Aryl For

And/or R³And R⁴In, the C substituted or unsubstituted₂-C₃₀Heteroaryl is substituted or unsubstituted following groups:

7. application according to any one of claims 1 to 3, which is characterized in that

In the preparation method such as formula IV compound represented, the gas in the gas shield is nitrogen or argon gas；

And/or in the preparation method such as formula IV compound represented, the organic solvent is nitrile solvents, aromatic hydrocarbons One of class solvent, halogenated aryl hydrocarbon class solvent, halogenated alkanes solvents, ketones solvent and amide solvent are a variety of；

And/or in the preparation method such as formula IV compound represented, the copper catalyst be copper powder, cuprous iodide, Stannous chloride, cuprous bromide, copper chloride, copper bromide, copper acetate, cuprous acetate, four acetonitrile hexafluorophosphoric acid copper, four acetonitrile tetrafluoro boron Sour copper, four acetonitrile copper trifluoromethanesulfcomposites, copper trifluoromethanesulfcomposite or thiophenic acid are cuprous；

And/or in the preparation method such as formula IV compound represented, the dinitrogen ligand is chiral dinitrogen ligand；

And/or in the preparation method such as formula IV compound represented, the alkali is the alkali metal salt or phenol sodium of alcohol；

And/or in the preparation method such as formula IV compound represented, the temperature of the reaction is -40~0 DEG C.

8. the use as claimed in claim 7, which is characterized in that

In the preparation method such as formula IV compound represented, the nitrile solvents are acetonitrile；

And/or in the preparation method such as formula IV compound represented, the aromatic hydrocarbon solvent is toluene；

And/or in the preparation method such as formula IV compound represented, the halogenated aryl hydrocarbon class solvent is chlorobenzene, fluorine One of benzene and benzotrifluoride are a variety of；

And/or in the preparation method such as formula IV compound represented, the halogenated alkanes solvents are methylene chloride And/or dichloroethanes；

And/or in the preparation method such as formula IV compound represented, the ketones solvent is acetone；

And/or in the preparation method such as formula IV compound represented, the amide solvent is N, N- dimethyl methyl Amide and/or DMAC N,N' dimethyl acetamide；

And/or in the preparation method such as formula IV compound represented, the copper catalyst is four acetonitrile hexafluorophosphoric acids Copper, four acetonitrile copper tetrafluoroborates, four acetonitrile copper trifluoromethanesulfcomposites or copper trifluoromethanesulfcomposite；

And/or in the preparation method such as formula IV compound represented, the chiral dinitrogen ligand is chiral double oxazoles Quinoline ligand One of or it is a variety of, wherein R^3a、R^3b、R^3cAnd R^3dIt independently is C₁-C₁₀Alkyl or C₆-C₃₀The C that aryl replaces₁-C₁₀Alkyl； R^4a、R^5a、R^4bAnd R^5bIt independently is hydrogen, C₁-C₁₀Alkyl, C₆-C₃₀Aryl or R^4aAnd R^5a、R^4bAnd R^5bCoupled carbon atom It is formed together C₃-C₁₀Naphthenic base；R^6a、R^6bAnd R^6cIt independently is hydrogen, C₁-C₁₀Alkyl, halogen,Cyano, fluoroform Base or C₆-C₃₀Aryl；R⁸For C₁-C₁₀Alkyl；N is 1,2,3 or 4；When n is 2,3 or 4, R^6aAnd R^6bIt is identical or different；

And/or in the preparation method such as formula IV compound represented, the alkali is R^a-ONa、R^b-OK、R^c- OLi andOne of or it is a variety of, wherein R^a、R^bAnd R^cIt independently is methyl, ethyl, n-propyl, isopropyl, positive fourth Base, isobutyl group or tert-butyl；R^a1、R^a2、R^a3、R^a4And R^a5It independently is hydrogen, halogen, C₁-C₁₀Alkyl orR⁹For C₁- C₁₀Alkyl；

And/or in the preparation method such as formula IV compound represented, the temperature of the reaction is -10~0 DEG C.

9. application as claimed in claim 8, which is characterized in that in the preparation method such as formula IV compound represented, The copper catalyst is four acetonitrile hexafluorophosphoric acid copper；

And/or in the preparation method such as formula IV compound represented, the dinitrogen ligand, R^3a、R^3b、R^3c、R^3d、 R^4a、R^5a、R^4b、R^5b、R^6a、R^6b、R^6cAnd R⁸In, the C₁-C₁₀Alkyl is C₁-C₆Alkyl；The C₆-C₃₀What aryl replaced C₁-C₁₀Alkyl is C₆-C₁₄The C that aryl replaces₁-C₆Alkyl；Work as R^4aAnd R^5a、R^4bAnd R^5bCoupled carbon atom is formed together C₃-C₁₀When naphthenic base, the C₃-C₁₀Naphthenic base is C₃-C₇Naphthenic base；R^6a、R^6bAnd R^6cIn, the halogen is F, Cl, Br Or I；

And/or in the preparation method such as formula IV compound represented, the preparation such as formula IV compound represented In method, the alkali, R^a1、R^a2、R^a3、R^a4And R^a5In, the halogen is F, Cl, Br or I；R^a1、R^a2、R^a3、R^a4、R^a5With R⁹In, the C₁-C₁₀Alkyl is C₁-C₆Alkyl.

10. application as claimed in claim 9, which is characterized in that in the preparation method such as formula IV compound represented, The dinitrogen ligand is chiral dinitrogen ligand, R^3a、R^3b、R^3c、R^3d、R^4a、R^5a、R^4b、R^5b、R^6a、R^6b、R^6cAnd R⁸In, it is described C₁-C₆Alkyl be methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl, n-hexyl and they Various isomers；The C₆-C₁₄The C that aryl replaces₁-C₆Alkyl is benzyl；The C₃-C₇Naphthenic base is cyclopropyl, ring fourth Base, cyclopenta, cyclohexyl or suberyl；

And/or in the preparation method such as formula IV compound represented, the alkali, R^a1、R^a2、R^a3、R^a4、R^a5And R⁹ In, the C₁-C₆Alkyl is methyl, ethyl, n-propyl, isopropyl, normal-butyl, tert-butyl, isobutyl group, n-pentyl, n-hexyl Or their various isomers.

11. application according to any one of claims 1 to 3, which is characterized in that the compound represented such as formula IV In preparation method, the molar ratio of the copper catalyst and the dinitrogen ligand is 2:1-1:3；

And/or the dosage of the catalyst is the 1%-100% molar equivalent such as Formula II compound represented；

And/or the dosage of the dinitrogen ligand is the 1%-100% molar equivalent such as Formula II compound represented；

And/or it is described if Formula II compound represented and the molar ratio such as formula III compound represented are 1:1-1: 3；

And/or the dosage of the fluorine nitrogen type amination reagent shown in formula I is the compound represented such as Formula II 100%-400% molar equivalent；

And/or the dosage of the alkali is the 20%-200% molar equivalent such as Formula II compound represented.

12. application as claimed in any one of claims 1-3, which is characterized in that such as the preparation side of formula IV compound represented Method includes the following steps: under gas shield, by the mixed of the copper catalyst, the dinitrogen ligand and the organic solvent Object is closed, with fluorine nitrogen type amination reagent shown in formula I, such as Formula II compound represented, such as formula III compound represented and described Alkali mixing, carries out the reaction, and such as formula IV compound represented is made.

13. a kind of if fluorine nitrogen type amination reagent shown in formula I according to any one of claims 1 to 10 is in preparation 2,2- bis- Application in aryl ethyl aminated compounds, which is characterized in that it includes the following steps:

(1) under gas shield, in the organic solvent, in the copper catalyst and the dinitrogen ligand and the alkali Under the action of, by fluorine nitrogen type amination reagent shown in formula I, such as Formula II compound represented and such as formula III compound represented Reaction as follows is carried out, such as formula IV compound represented is made；

(2) under gas shield, in organic solvent, under the action of reducing agent, removing sulphur will be carried out such as formula IV compound represented 2,2- diaryl ethylamine compounds shown as a formula V are made in the reaction of acyl protecting groups；

Wherein, R¹、R²、R³And R⁴Definition it is as described in claim 1；R^2’For C₁-C₁₀Straight chained alkyl or R^1a；R^1aDefinition and R¹ It is identical.

14. application as claimed in claim 13, which is characterized in that

In the preparation method of 2,2- diaryl ethyl aminated compounds shown as a formula V, each item of reaction described in step (1) Part is as described in any one of claim 1-12；

And/or in the preparation method of 2,2- diaryl ethyl aminated compounds shown as a formula V, in step (2), described has Solvent is alcohols solvent；

And/or in the preparation method of 2,2- diaryl ethyl aminated compounds shown as a formula V, in step (2), described is gone back Former agent is magnesium powder；

And/or in the preparation method of 2,2- diaryl ethyl aminated compounds shown as a formula V, in step (2), described is anti- The temperature answered is room temperature；

And/or in the preparation method of 2,2- diaryl ethyl aminated compounds shown as a formula V, in step (2), described is gone back Former agent is 2:1-100:1 with the molar ratio such as formula IV compound represented.

15. application as claimed in claim 14, which is characterized in that 2,2- diaryl ethyl aminated compounds shown as a formula V Preparation method in, in step (2), the alcohols solvent be methanol；

And/or the reducing agent and the molar ratio such as formula IV compound represented are 5:1-50:1.

16. a kind of fluorine nitrogen type amination reagent shown in formula I is