CN112812133B - Alpha, alpha-difluoroallyl organometallic compound and preparation method and application thereof - Google Patents

Alpha, alpha-difluoroallyl organometallic compound and preparation method and application thereof Download PDF

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CN112812133B
CN112812133B CN202110115070.1A CN202110115070A CN112812133B CN 112812133 B CN112812133 B CN 112812133B CN 202110115070 A CN202110115070 A CN 202110115070A CN 112812133 B CN112812133 B CN 112812133B
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冯超
王成强
李依
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Nanjing Tech University
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Abstract

The invention discloses an alpha, alpha-difluoroallyl organometallic compound, a preparation method and application thereof. In the invention, cuprous iodide, sodium tert-butoxide, a raw material A, 1-difluoroallene and methanol are sequentially added into a reaction solvent in a nitrogen atmosphere to obtain a mixture; wherein the raw material A is diboronic acid pinacol ester or a composition, the composition is 1, 3-bis (2,4, 6-trimethylphenyl) imidazole chloride and (dimethyl phenyl silyl) boronic acid pinacol ester, the mixture is stirred at room temperature and reacts until the reaction is finished, and the reaction product is filtered and separated by a short silica gel column or separated by silica gel column chromatography to obtain the alpha, alpha-difluoro allyl organic metal compound. The preparation method can be carried out at room temperature, is simple and convenient to operate, adopts simple and easily-obtained raw materials, has low cost, good functional group compatibility and wide substrate application range, and the obtained compound has wide application prospect in research and development of medicines and materials.

Description

Alpha, alpha-difluoroallyl organometallic compound and preparation method and application thereof
Technical Field
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to an alpha, alpha-difluoroallyl organometallic compound, and a preparation method and application thereof.
Background
The alpha, alpha-difluoroallyl borate and the allyl silicon compounds as a special class of fluorine-containing organic metal compounds generally have unique physicochemical properties and biological activities, and relevant researches have important values in the fields of novel functional material development, drug research and development, organic synthetic chemistry and the like. Therefore, the production of α, α -difluoroallylboronic acid esters and allylsilicon-based compounds has received increasing attention in recent years.
At present, the preparation of alpha, alpha-difluoroallylborate and allylsilicon compounds mainly depends on multi-step reactions or defluorinated boronization or defluorination reactions of alpha-trifluoromethyl olefin. For example, in the method disclosed in document 1(Ramachandran, p.v.; Tafelska-Kaczmarek, a.; Chatterjee, a.j.org.chem.2012,77,9329), a gaseous difluoroalkenyl lithium reagent formed in situ from 1, 1-difluoroethylene and sec-butyl lithium is substituted with iodomethyl diisopropyl borate to form a primary α, α -difluoroallyl borate compound, and the specific reaction process is as follows:
Figure BDA0002920293400000011
document 2(Liu, Y.; Zhou, Y.; ZHao, Y.; Qu, J.Org.Lett.2017,19,946) discloses a process in which ferrous chloride is capable of catalyzing, at 65 ℃, the defluorinated boronation of an alpha-trifluoromethylolefin with a pinacol ester of diboronic acid, in a first order (R)2Is H) and two (R)2The method provides a new method for preparing the H) alpha, alpha-difluoroallyl borate compound, and the specific reaction process is as follows:
Figure BDA0002920293400000012
in the method disclosed in document 3(Gao, p.; Yuan, c.; Zhao, y.; Shi, z. chem 2017,4,2201), under the catalysis of cuprous iodide and a chiral phosphine ligand of a ferrocene skeleton, an optically pure secondary α, α -difluoroallyl borate compound can be obtained by an asymmetric dehydroxyboration reaction of α -trifluoromethyl olefin, and the compound can be further oxidized to generate a chiral secondary α, α -difluoroallyl alcohol compound, and the specific reaction process is as follows:
Figure BDA0002920293400000021
in the method disclosed in document 4(Shi, G. -q.; Huang, X. -h.tetrahedron Lett.1996,37,5401), malonic ester is subjected to twice substitution reactions under alkaline conditions to generate a compound M, and the compound M is subjected to decarboxylation and hydrogen bromide elimination reactions to obtain a primary alpha, alpha-difluoroallylsilicon compound, wherein the specific reaction process is as follows:
Figure BDA0002920293400000022
in the method disclosed in document 5 (Paotii, P.H.S.; Pozo, J.d.; Mikus, M.S.; Lee, J.; Koh, M.J.; Romiti, F.; Torker, S.; Hoveyda, A.H.J.am.Chem.Soc.2019,141,19917), under catalysis of cuprous chloride and a chiral azacarbene (NHC) ligand and activation of a base (lithium tert-butoxide), a novel asymmetric desflurosilylation reaction of α -trifluoromethylolefin and (dimethylsilyl) pinacol borate can be carried out, providing a novel process for the preparation of chiral secondary α, α -difluoroallylic silicon compounds, as follows:
Figure BDA0002920293400000031
in the method disclosed in document 6(Gao, p.; Gao, l.; Xi, l.; Zhang, z.; Li, s.; Shi, z. org. chem. front.2020,7,2618), a chiral secondary α, α -difluoroallylsilicon compound can be similarly produced by an asymmetric dehydrofluorination reaction of α -trifluoromethylolefin and (dimethylsilyl) boronic acid pinacol ester at 50 ℃ using cuprous chloride as a catalyst precursor, and azacarbene as a ligand, and the specific reaction process is as follows:
Figure BDA0002920293400000032
however, these strategies have some disadvantages, such as difficulty in synthesis of starting materials, complicated operation, requirement of multi-step synthesis, harsh reaction conditions (high or low reaction temperature, requirement of metal reagents, etc.), large limitation of substrate range, etc.
It is worth pointing out that no effective method exists for synthesizing tertiary alpha, alpha-difluoroallyl borate and allylsilicon compounds. Therefore, the development of a novel strategy for preparing alpha, alpha-difluoroallyl borate and allyl silicon compounds with various structures still has important significance, and particularly, the preparation of the tertiary alpha, alpha-difluoroallyl borate and the allyl silicon compounds further expands the application of the metal compounds. Such research may represent significant research value in related scientific research and productive life.
Disclosure of Invention
The invention aims to provide a preparation method of an alpha, alpha-difluoroallyl organometallic compound, and aims to solve the problems that the existing synthetic method is difficult in synthesis of starting raw materials, complex in operation, required in multi-step synthesis, harsh in reaction conditions, large in substrate range limitation and the like.
It is still another object of the present invention to provide the above alpha, alpha-difluoroallyl organometallic compound and its use.
The present invention is achieved by an alpha, alpha-difluoroallyl organometallic compound having the chemical formula shown in the following formula (I):
Figure BDA0002920293400000041
in the formula (I), R1Is hydrogen, phenethyl, 4-methoxyphenylethyl, 4-triisopropylsiloxybenzeneEthyl, 4-cyanophenylethyl, 4-bromophenylethyl, piperonylethyl, 4-triisopropylsilylethynylphenylethyl, 4-phenylethynylphenylethyl, E-hex-3-enyl, E-4-phenyl-but-3-enyl, 3-chloro-N-propyl, 3- (4-methoxybenzyloxy) propyl, 1-naphthalenylmethoxypropoxymethyl, 2-dimethyl-tert-butylsilyloxyethyl, tert-butyldiphenylsilyloxymethyl, 2- (1, 3-dioxane) -ethyl, 5-methyl-furan-2-ethyl, 5-bromo-N-methyl-indol-3-ethyl, 2, 6-dimethyloct-2-en-8-oxymethyl, Alkyl groups or functionalized alkyl groups such as pterostilbene derivative groups, ethyl groups, vitamin derivative groups, and the like;
R2alkyl groups or functionalized alkyl groups such as N-nonyl, phenethyl, 2-methoxyphenethyl, 4-fluorophenethyl, 1-naphthylmethoxyethyl, 5-methyl-furan-2-ethyl, thiophene-3-ethyl, N-methyl-indole-3-propyl, 5-carbazole-1-N-pentyl, piperonyl propyl, dimethylbenzyl, 4-methoxydimethylbenzyl, 4-trifluoromethylphenylcyclopropyl, methyl, ethyl, 3-chloro-N-propyl, tert-butyldiphenylsiloxymethyl, vitamin derivative groups, and the like;
R3is a boric acid ester group such as pinacol boric acid ester group, phenyl dimethyl silicon group and the like or silicon group.
The invention further discloses a preparation method of the alpha, alpha-difluoroallyl organometallic compound, which comprises the following steps:
(1) under the nitrogen atmosphere, cuprous iodide, sodium tert-butoxide, a raw material A, 1-difluoroallene and methanol are mixed according to a molar ratio of (0.001-0.1): (0.1-5.0): (1.0-5.0): 1.0: (1.0-100) sequentially adding the mixture into a reaction solvent to obtain a mixture; wherein the raw material A is diboron pinacol ester or a composition, and the composition is prepared from the following raw materials in a molar ratio of (0.001-0.1): 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, (dimethylsilyl) boronic acid pinacol ester (1.0-5.0);
(2) and (2) stirring the mixture in the step (1) at room temperature to react until the reaction is finished, and filtering and separating the reaction product through a short silica gel column or separating the reaction product through silica gel column chromatography to obtain the alpha, alpha-difluoroallyl organometallic compound.
Preferably, in step (ii)In the step (1), the 1, 1-difluoroallene is R1And/or R2A group-substituted 1, 1-difluoroallene; wherein R is1Is hydrogen, phenethyl, 4-methoxyphenylethyl, 4-triisopropylsilylphenylethyl, 4-cyanophenylethyl, 4-bromophenylethyl, piperonylethyl, 4-triisopropylsilylethynylphenylethyl, 4-phenylethynylphenylethyl, E-hex-3-enyl, E-4-phenyl-but-3-enyl, 3-chloro-N-propyl, 3- (4-methoxybenzyloxy) propyl, 1-naphthylmethoxypropoxymethyl, 2-dimethyl-tert-butylsilyloxyethyl, tert-butyldiphenylsilyloxymethyl, 2- (1, 3-dioxane) -ethyl, 5-methyl-furan-2-ethyl, 5-bromo-N-methyl-indole-3-ethyl, alkyl or functionalized alkyl such as 2, 6-dimethyloct-2-en-8-oxymethyl, pterostilbene derivative, ethyl, vitamin derivative, etc.;
R2alkyl groups or functionalized alkyl groups such as N-nonyl, phenethyl, 2-methoxyphenethyl, 4-fluorophenethyl, 1-naphthylmethoxyethyl, 5-methyl-furan-2-ethyl, thiophene-3-ethyl, N-methyl-indole-3-propyl, 5-carbazole-1-N-pentyl, piperonyl propyl, dimethylbenzyl, 4-methoxydimethylbenzyl, 4-trifluoromethylphenylcyclopropyl, methyl, ethyl, 3-chloro-N-propyl, tert-butyldiphenylsiloxymethyl, vitamin derivative groups, and the like.
Preferably, in step (1), the reaction solvent is 1, 2-dichloroethane; in step (2), the mixture was stirred at room temperature for 12 h.
The invention further discloses the application of the alpha, alpha-difluoroallyl organometallic compound in the synthesis of novel fluorine-containing compounds or non-fluorine-containing compounds.
Preferably, the fluorine-containing compound comprises alpha, alpha-difluoroallyl alcohol compounds and derivatives thereof, and the non-fluorine-containing compound comprises tertiary propargyl silicon compounds.
The invention overcomes the defects of the prior art and provides an alpha, alpha-difluoroallyl organometallic compound and a preparation method and application thereof. Under the nitrogen atmosphere, cuprous iodide, sodium tert-butoxide, a raw material A, 1-difluoroallene and methanol are mixed according to a molar ratio of (0.001-0.1): (0.1-5.0): (1.0-5.0): 1.0: (1.0-100) sequentially adding the mixture into a reaction solvent to obtain a mixture; wherein the raw material A is diboron pinacol ester or a composition, and the composition is prepared from the following raw materials in a molar ratio of (0.001-0.1): 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, (dimethylsilyl) boronic acid pinacol ester (1.0-5.0); and stirring the mixture at room temperature to react until the reaction is finished, and filtering and separating the reaction product by using a short silica gel column or separating the reaction product by using silica gel column chromatography to obtain the alpha, alpha-difluoroallyl organometallic compound.
In the preparation method of the present invention, when the starting material a is pinacol diboron, the reaction equation of the α, α -difluoroallyl organometallic compound is as follows:
Figure BDA0002920293400000061
the alpha, alpha-difluoroallyl organometallic compound is an alpha, alpha-difluoroallyl borate compound containing tertiary carbon or quaternary carbon center.
In the preparation method, when the raw material A is a mixture of the following raw materials in a molar ratio of (0.001-0.1): (1.0 to 5.0) 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, pinacol ester of (dimethylsilyl) boronic acid, the reaction equation of the alpha, alpha-difluoroallyl organometallic compound is as follows:
Figure BDA0002920293400000062
the alpha, alpha-difluoroallyl organometallic compound is an alpha, alpha-difluoroallyl silicon compound containing tertiary carbon or quaternary carbon center.
Therefore, in the invention, 1-difluoro allene is used as a raw material, and under the activation action of alkali, a copper catalyst is reacted with B2pin2Or PhMe2Si-Bpin can form an organic copper-boron or copper-silicon intermediate in situ, and then carbon-carbon double bonds (double bonds without fluorine substituent) rich in electrons in 1, 1-difluoroallene and the obtained copper-boron or copper-silicon intermediate are subjected to processes of coordination, migration insertion, protonation and the likeAlpha, alpha-difluoroallyl borate compounds or alpha, alpha-difluoroallyl silicon compounds containing quaternary carbon or tertiary carbon centers can be obtained.
Fluorine atoms or fluorine-containing groups are introduced into small molecules, so that the lipid solubility, membrane permeability, metabolic stability and the like of the small molecules can be obviously changed, and related researches are widely applied to the fields of medicines, materials and the like. Among them, alpha-difluoroolefin is used as a carbonyl isostere which is commonly used and plays an important role in the development of modern new drugs. The alpha, alpha-difluoroallyl borate compound or the alpha, alpha-difluoroallyl silicon compound containing the quaternary carbon or tertiary carbon center prepared by the invention has great development potential in the research and development of small molecule drugs. In addition, the two kinds of metal organic compounds can prepare more fluorine-containing or non-fluorine-containing compounds through the existing coupling reaction, and the fluorine-containing or non-fluorine-containing compounds can also play more important roles in organic synthesis.
Compared with the defects and shortcomings of the prior art, the invention has the following beneficial effects:
(1) the preparation method can be carried out at room temperature, is simple and convenient to operate, adopts simple and easily-obtained raw materials, and has low cost, good functional group compatibility and wide substrate application range;
(2) the alpha, alpha-difluoroallyl organometallic compound has a wide application prospect in research and development of medicines and materials as a class of alpha, alpha-difluoroolefin compounds containing quaternary carbon or tertiary carbon centers with novel structures, and particularly can be used for preparing and obtaining tertiary alpha, alpha-difluoroallyl borate and allyl silicon compounds which are difficult to synthesize by using the existing method.
Drawings
FIG. 1 is a hydrogen spectrum of Compound 1 in the example of the present invention;
FIG. 2 is a hydrogen spectrum of compound 37 in the example of the present invention;
FIG. 3 is a hydrogen spectrum of compound 67 in the example of the present invention;
FIG. 4 is a hydrogen spectrum of compound 68 in an example of the present invention;
FIG. 5 is a hydrogen spectrum of compound 69 in the example of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1
(1) Under a nitrogen atmosphere, 0.02mmol of cuprous iodide, 0.2mmol of sodium tert-butoxide, 0.3mmol of pinacol diboron, 0.2mmol of (5, 5-difluoro-3-methylpentyl-3, 4-diene) -1-benzene and 0.4mmol of methanol were sequentially added to 1.2mL of 1, 2-dichloroethane to obtain a mixture;
(2) stirring the mixture at room temperature to react until the reaction is finished (12h), and filtering and separating the reaction product by a short silica gel column to obtain the alpha, alpha-difluoroallyl borate compound 1 containing the quaternary carbon center, wherein the structural formula is shown as follows:
Figure BDA0002920293400000081
the hydrogen spectrum of this compound 1 is shown in FIG. 1.
Examples 2 to 36
Examples 2 to 36 are the same as example 1 except that the substituent R in 1, 1-difluoroallene1And R2Respectively as follows:
TABLE 1 examples 2 to 46
Figure BDA0002920293400000082
Figure BDA0002920293400000091
Example 37
(1) 0.005mmol of cuprous iodide, 0.02mmol of sodium tert-butoxide, 0.005mmol of 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, 0.1mmol of (5, 5-difluoro-3-methylpentyl-3, 4-diene) -1-benzene, 0.18mmol of (dimethylsilyl) boronic acid pinacol ester and 0.05mL of methanol were successively added to 0.45mL of 1, 2-dichloroethane under a nitrogen atmosphere to obtain a mixture.
(2) And (3) stirring the mixture at room temperature to react until the reaction is finished (12h), and separating the reaction product by silica gel column chromatography to obtain the alpha, alpha-difluoroallylic silicon compound 37 containing the quaternary carbon center, wherein the structural formula is shown as follows:
Figure BDA0002920293400000101
the hydrogen spectrum of this compound 37 is shown in FIG. 2.
Examples 38 to 62
Examples 38 to 62 are substantially the same as example 37 except that the substituent R in 1, 1-difluoroallene1And R2Respectively as follows:
Figure BDA0002920293400000102
Figure BDA0002920293400000111
example 63
This example is substantially the same as example 1, except that in step (1): 0.0002mmol of cuprous iodide, 0.02mmol of sodium tert-butoxide, 0.2mmol of pinacol diboron, 0.2mmol of 1- (5, 5-difluoro-3-methyl-3, 4-pentadienyl) benzene and 0.2mmol of methanol were sequentially added to a reaction flask containing 1.2mL of 1, 2-dichloroethane under a nitrogen atmosphere to obtain a mixture.
Example 64
This embodiment is substantially the same as the embodiment, except that in step (1): 0.0001mmol of cuprous iodide, 0.01mmol of sodium tert-butoxide, 0.0001mmol of 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, 0.1mmol of 1- (5, 5-difluoro-3-methyl-3, 4-pentadienyl) benzene, 0.1mmol of (dimethylsilyl) boronic acid pinacol ester and 0.1mmol of methanol were sequentially added to a reaction flask containing 0.5mL of 1, 2-dichloroethane under a nitrogen atmosphere to obtain a mixture.
Example 65
This example is substantially the same as example 1, except that in step (1): 0.02mmol of cuprous iodide, 1.0mmol of sodium tert-butoxide, 1.0mmol of pinacol diboron, 0.2mmol of 1- (5, 5-difluoro-3-methyl-3, 4-pentadienyl) benzene and 20mmol of methanol were sequentially added to a reaction flask containing 1.2mL of 1, 2-dichloroethane under a nitrogen atmosphere to obtain a mixture.
Example 66
This embodiment is substantially the same as the embodiment, except that in step (1): 0.01mmol of cuprous iodide, 0.5mmol of sodium tert-butoxide, 0.01mmol of 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, 0.1mmol of 1- (5, 5-difluoro-3-methyl-3, 4-pentadienyl) benzene, 0.5mmol of (dimethylsilyl) boronic acid pinacol ester and 10mmol of methanol were sequentially added to a reaction flask containing 0.5mL of 1, 2-dichloroethane under a nitrogen atmosphere to obtain a mixture.
Example 67
(1) Under a nitrogen atmosphere, 0.02mmol of cuprous iodide, 0.2mmol of sodium tert-butoxide, 0.3mmol of pinacol diboron, 0.2mmol of (5, 5-difluoro-3-methylpentyl-3, 4-diene) -1-benzene and 0.4mmol of methanol were sequentially added to 1.2mL of 1, 2-dichloroethane to obtain a mixture;
(2) and (3) stirring the mixture at room temperature to react until the reaction is finished (12h), and filtering and separating the reaction product by using a short silica gel column to obtain the alpha, alpha-difluoroallyl borate compound 1 containing the quaternary carbon center.
(3) The α, α -difluoroallylboronic acid ester compound 1 obtained above was added to a reaction tube containing 1.0mL of tetrahydrofuran in an air atmosphere, and aq.naoh (2.0M,0.6mmol) and 30% aq.h were simultaneously dropped into the reaction tube while stirring at room temperature2O2(1.2mmol), after the addition, the reaction is continued for 3 hours at room temperature, the reaction solution is diluted by a proper amount of water, then is extracted by ethyl acetate, washed by brine, dried by anhydrous sodium sulfate, and then the filtrate obtained by filtration is subjected to reduced pressure distillation to remove the solvent, thus obtaining a crude product of the compound 67, and the crude product is purified by silica gel column chromatography to obtain a pure product.
The reaction equation involved in the embodiment of the present invention is as follows:
Figure BDA0002920293400000131
the hydrogen spectrum of compound 67 is shown in FIG. 3.
Example 68
Under nitrogen atmosphere, 0.8LiAlH4And 0.2mmol of alpha, alpha-difluoroallyl alcohol compound 67 are sequentially added into 1.0mL of anhydrous tetrahydrofuran, then the mixture is stirred and reacted for 12 hours at the temperature of 80 ℃, after the reactant is cooled to the room temperature, the reactant is quenched by proper amount of water, then the reactant is extracted by ethyl acetate, washed by brine, dried by anhydrous sodium sulfate, then the filtrate obtained by filtering the reactant by diatomite is subjected to reduced pressure distillation to remove the solvent, thus obtaining a crude product of the compound 68, and the crude product can be purified by silica gel column chromatography to obtain a pure product. The reaction equation related to the embodiment of the invention is shown as follows:
Figure BDA0002920293400000132
the hydrogen spectrum of compound 68 is shown in FIG. 4.
Example 69
Under the nitrogen atmosphere, 0.2mmol of alpha, alpha-difluoroallylsilicon compound 37 is added into 1.0mL of anhydrous tetrahydrofuran, then the reaction liquid is cooled to-78 ℃, BuLi (1.6M in THF, 3.0equiv.) is added into the reaction liquid dropwise at-78 ℃, the mixture is continuously stirred and reacted for 3 hours after the reaction is finished, then the reaction product is naturally raised to the room temperature, the mixture is continuously stirred and reacted for 3 hours, the reaction product is quenched by proper amount of water, then the ethyl acetate is used for extraction, the brine is washed, the anhydrous sodium sulfate is dried, the filtrate obtained by filtration is subjected to reduced pressure distillation to remove the solvent, so that the crude product of the compound 69 can be obtained, and the crude product can be purified by silica gel column chromatography to obtain a pure product. The reaction equation related to the embodiment of the invention is shown as follows:
Figure BDA0002920293400000141
the hydrogen spectrum of compound 69 is shown in FIG. 5.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.

Claims (2)

1. A process for the preparation of an α, α -difluoroallyl organometallic compound, the process comprising the steps of:
(1) under the nitrogen atmosphere, cuprous iodide, sodium tert-butoxide, a raw material A, a 1, 1-difluoroallene compound and methanol are mixed according to the molar ratio of (0.001-0.1): (0.1-5.0): (1.0-5.0): 1.0: (1.0-100) sequentially adding the mixture into a reaction solvent to obtain a mixture; wherein the raw material A is diboron pinacol ester or a composition, and the composition is prepared from the following raw materials in a molar ratio of (0.001-0.1): 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride, (dimethylsilyl) boronic acid pinacol ester (1.0-5.0);
(2) stirring the mixture in the step (1) at room temperature to react until the reaction is finished, and filtering and separating the reaction product by a short silica gel column or separating the reaction product by silica gel column chromatography to obtain an alpha, alpha-difluoroallyl organometallic compound;
in the step (1), the 1, 1-difluoroallene compound is R1And/or R2A group-substituted 1, 1-difluoroallene; wherein R is1Is hydrogen, phenethyl, 4-methoxyphenylethyl, 4-triisopropylsilylphenylethyl, 4-cyanophenylethyl, 4-bromophenylethyl, piperonylethyl, 4-triisopropylsilylethynylphenylethyl, 4-phenylethynylphenylethyl, E-hex-3-enyl, E-4-phenyl-but-3-enyl, 3-chloro-N-propyl, 3- (4-methoxybenzyloxy) propyl, 1-naphthylmethoxypropoxymethyl, 2-dimethyl-tert-butylsilyloxyethyl, tert-butyldiphenylsilyloxymethyl, 2- (1, 3-dioxane) -ethyl, 5-methyl-furan-2-ethyl, 5-bromo-N-methyl-indole-3-ethyl, 2, 6-dimethyloct-2-en-8-oxymethyl, ethyl;
R2is n-nonyl, phenethyl, 2-methoxyphenethyl, 4-fluoroPhenethyl, 1-naphthylmethoxyethyl, 5-methyl-furan-2-ethyl, thiophene-3-ethyl, N-methyl-indole-3-propyl, 5-carbazole-1-N-pentyl, piperonylpropyl, dimethylbenzyl, 4-methoxydimethylbenzyl, 4-trifluoromethylphenylcyclopropyl, methyl, ethyl, 3-chloro-N-propyl, tert-butyldiphenylsiloxymethyl.
2. The method for producing an α, α -difluoroallyl organometallic compound according to claim 1, wherein in the step (1), the reaction solvent is 1, 2-dichloroethane; in step (2), the mixture was stirred at room temperature for 12 h.
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