CN114716345A

CN114716345A - Method for deoxygenation functionalization and deoxygenation activation of alcohols and alcohol-functionalized materials

Info

Publication number: CN114716345A
Application number: CN202110014657.3A
Authority: CN
Inventors: 汪清民; 李成林; 于国清; 陈育明; 宋红健; 何如; 刘玉秀
Original assignee: Shandong Boyuan Pharmaceutical Chemical Co ltd; Nankai University
Current assignee: Shandong Boyuan Pharmaceutical Chemical Co ltd; Nankai University
Priority date: 2021-01-06
Filing date: 2021-01-06
Publication date: 2022-07-08

Abstract

The invention relates to the field of organic synthesis, and discloses a method for carrying out deoxidation functionalization and deoxidation activation on alcohol and an alcohol functionalized substance, wherein the method comprises the following steps: (1) in a first solvent, in the presence of an activating agent, carrying out deoxidation and activation on alcohol to obtain an iodo intermediate; (2) functionalizing the iodo intermediate in a second solvent in the presence of a nucleophile. The method provided by the invention is simple and convenient to operate and easy to separate and purify.

Description

Method for deoxygenation functionalization and deoxygenation activation of alcohols and alcohol-functionalized materials

Technical Field

The invention relates to the field of organic synthesis, in particular to a method for performing deoxygenation functionalization and deoxygenation activation on alcohol and an alcohol functionalized substance.

Background

As a class of cheap and easily available compounds, the deoxidation functionalization of alcohol is always a research hotspot in the fields of organic synthetic chemistry, pharmaceutical chemistry and the like. The deoxygenation functionalization of alcohols is mainly divided into a polarization reaction process (Tetrahedron Lett.1980,21, 801-804; Synlett 2019,30,1508-1524), a radical reaction process (Tetrahedron Lett.1985,26, 757-760; J.Am.chem.Soc.2020,142,16787-16794) and a metal-catalyzed reaction process (J.Am.chem.Soc.2012,134, 14638-14641; chem.Commun.2015,51,2683-2686) according to the cleavage formation mode of chemical bonds during the reaction.

Of these, direct nucleophilic substitution is the most desirable, H₂O is taken as a unique byproduct, and has the advantages of environmental friendliness and atom economy. However, the hydroxyl group is a difficult leaving group, and direct nucleophilic substitution functionalization of the alcohol is difficult to perform, and the alcohol needs to be activated first.

Conventional reagents including thionyl chloride, sulphuryl chloride, etc. can activate alcohols but produce metered strong acid waste. The Appel reaction and the Garegg-Samuelsson reaction (J.Am. chem. Soc.2007,129, 9566-9567; J.chem. Soc., Perkin Trans.11980, 2866-2869) are efficient methods of hydroxyhalogenation but use either a highly toxic CX4 reagent or produce phosphine oxide byproducts that are difficult to separate. The Mitsunobu reaction (chem. rev.2009,109,2551-2651) is a common method of alcohol deoxygenation functionalization, but it has the property of alcohol configuration inversion, and it requires an acidic nucleophile, limits the range of nucleophiles, and produces phosphine oxide by-products that are difficult to separate in a metered amount, which is not in accordance with the principles of atom economy.

Therefore, it is of great interest to develop a deoxygenation functionalization process for alcohols that is safe and easy to handle and isolate and purify.

Disclosure of Invention

The present invention aims to overcome the above-mentioned defects of the prior art and provide a deoxygenation functionalization method for alcohol, which is simple and convenient to operate and easy to separate and purify.

In order to achieve the above object, a first aspect of the present invention provides a method for deoxygenating functionalization of an alcohol, the method comprising:

(1) in a first solvent, in the presence of an activating agent, carrying out deoxidation and activation on alcohol to obtain an iodo intermediate;

(2) functionalizing said iodide intermediate in a second solvent in the presence of a nucleophile to provide an alcohol-functionalized material;

wherein the activator has a structure represented by formula (I);

wherein, in the formula (I),

R^a、R^band R^cEach independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl, and R^a、R^bAnd R^cWherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine.

In a second aspect the present invention provides an alcohol functionalised material selected from at least one of the following compounds:

in a third aspect, the present invention provides a method of deoxygenation activation of an alcohol, the method comprising:

deoxygenating and activating an alcohol in a first solvent in the presence of an activating agent, wherein the activating agent has a structure shown in a formula (I);

wherein, in the formula (I),

Compared with the prior art, the invention has at least the following advantages:

the method provided by the invention is simple and convenient to operate and easy to separate and purify, the substrate of the method is wider in application range, the nucleophilic reagent can be selected from various types, the product yield is high, the byproducts are few, the generated byproducts (such as silyl ether and iodized salt) can be removed or recycled by distillation or washing, no acid waste is generated, and no harmful influence is caused on the environment.

In particular, the present invention provides methods, partially sulfurized products and aminated products capable of maintaining the optical configuration of the starting substrate alcohol.

Additional features and advantages of the invention will be described in the detailed description which follows.

Detailed Description

The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.

In this context, explanations are provided first for the following terms:

C_1-20the alkyl group of (a) refers to a group having an alkyl group of 1 to 20 carbon atoms in total (e.g., 1,2, 3, 4, 5, 6,7, 8, 9,10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20), and may be a straight-chain, branched or cyclic alkyl group, including but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, cyclohexyl, and the like.

C_6-20The aryl group of (a) refers to a group having a total number of carbon atoms of 6 to 20 (e.g., 6,7, 8, 9,10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20) aryl groups, including but not limited to phenyl, naphthyl, anthracenyl, and the like.

“C_1-10Alkyl of (2), "" C_6-15Aryl of (2), "" C_1-5Alkyl of (2), "" C_6-10Aryl of (2)' with the aforementioned "C_1-20Alkyl of and C_6-20The definition of "aryl" is similar, only the number of carbon atoms is different.

As previously mentioned, a first aspect of the present invention provides a method of deoxygenating a functionality of an alcohol, the method comprising:

wherein the activator has a structure represented by formula (I);

wherein, in the formula (I),

R^a、R^band R^cEach independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl, and R^a、R^bAnd R^cWherein the substituents optionally present are each independently selected from halogen, alkoxyAt least one of alkyl, aryl, heteroaryl and amino.

According to the present invention, the optionally present substituent means that a substituent may be present or absent, and the substitution position and the number of substitutions of each optionally present substituent are not particularly limited, and substitution may be performed at any substitutable position.

Preferably, in formula (I),

R^a、R^band R^cEach independently selected from substituted or unsubstituted C_1-20Alkyl, substituted or unsubstituted C_6-20And R is an aryl group of^a、R^bAnd R^cWherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine.

More preferably, in formula (I),

R^a、R^band R^cEach independently selected from substituted or unsubstituted C_1-10Alkyl, substituted or unsubstituted C_6-15And R is an aryl group of^a、R^bAnd R^cWherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine.

Further preferably, the activator is selected from at least one of trimethyl iodosilane, triethyl iodosilane, triisopropyl iodosilane, tri-n-butyl iodosilane, tri-t-butyl iodosilane, dimethyl-t-butyl iodosilane, tricyclohexyl iodosilane and triphenyl iodosilane.

Still more preferably, the activator is trimethyliodosilane.

Preferably, the alcohol is a primary and/or secondary alcohol, the alcohol has the structure shown in formula (II), and the iodide intermediate has the structure shown in formula (II'):

in the formulae (II) and (II'),

R¹and R²Each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, and R¹And R²Wherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine.

Preferably, in the formulae (II) and (II'),

R¹and R²Each independently selected from the group consisting of hydrogen, substituted or unsubstituted C_1-20Alkyl and substituted or unsubstituted C_6-20And R is an aryl group of¹And R²Wherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine.

More preferably, in formula (II) and formula (II'),

R¹and R²Each independently selected from the group consisting of hydrogen, substituted or unsubstituted C_1-10Alkyl, substituted or unsubstituted C_6-15And R is an aryl group of¹And R²Wherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine.

Further preferably, in the formulae (II) and (II'),

R¹and R²Each independently selected from the group consisting of hydrogen, substituted or unsubstituted C_1-5Alkyl, substituted or unsubstituted C_6-10And R is an aryl group of¹And R²Wherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine.

Even more preferably, the alcohol is selected from at least one of the following compounds:

preferably, the method provided by the present invention is represented by the following formula (1):

in formula (1), HNu and Nu^-Represents at least one nucleophile selected from nitrogen-containing nucleophiles, sulfur-containing nucleophiles, carbon-containing nucleophiles, halogen-containing nucleophiles and oxygen-containing nucleophiles; nu represents at least one group selected from a nitrogen-containing group, a sulfur-containing group, a carbon-containing group, a halogen-containing group and an oxygen-containing group.

Preferably, in step (1), the molar ratio of the activator to the alcohol is 1 to 4: 1.

preferably, in step (1), the deoxidation activation conditions include: the temperature is from minus 20 ℃ to 100 ℃ and the time is 0.5 to 20 hours.

Preferably, in step (1), the deoxidation activation is performed under a protective atmosphere and a light-shielding condition.

According to a preferred embodiment of the present invention, in step (1), the alcohol is a chiral secondary alcohol, the iodide intermediate is a chiral iodide, and the iodide intermediate has an optical configuration opposite to that of the alcohol.

According to the invention, the optical configurations of the two substances are opposite to each other, which means that the optical configurations of the two substances are mutually inverted, for example, when the optical configuration of the alcohol is R type, the optical configuration of the iodide intermediate is S type.

Preferably, in step (1), the first solvent is at least one selected from the group consisting of dichloromethane, dichloroethane, chloroform, dioxane and acetonitrile, more preferably dichloromethane.

The amount of the first solvent used in the present invention is not particularly limited, and may be appropriately selected by those skilled in the art according to the needs.

According to the invention, step (1) further comprises desolvating the deoxygenated activated solution to obtain the iodide intermediate. The present invention is not particularly limited in specific operation of the desolvation, and may be carried out by a method of desolvation using a solvent existing in the art as long as the iodide intermediate can be obtained.

According to the invention, the reaction of step (2) can be carried out without further purification to obtain the iodide intermediate, and the operation is simple.

According to the present invention, in step (1), in addition to the iodide intermediate, although byproducts of silanol (e.g., trimethylsilanol) and silyl ether (e.g., hexamethylsilyl ether) may be generated, both the silanol and silyl ether byproducts can be recovered by distillation.

According to the invention, the deoxygenation functionalization of the alcohol means subjecting the alcohol to processes including deoxygenation amination, deoxygenation sulfurization, deoxygenation esterification, deoxygenation etherification, deoxygenation halogenation, deoxygenation carbonization, deoxygenation amidation, deoxygenation sulfonylation, etc.

Preferably, in step (2), the functionalization is selected from at least one of amination, sulfurization, carbonization, halogenation, amidation, sulfonylamination, esterification, and etherification.

More preferably, in step (2), the functionalization is selected from at least one of amination, sulfurization, sulfonylamination, esterification, and etherification.

Preferably, in step (2), the nucleophile is selected from at least one of a nitrogen-containing nucleophile, a sulfur-containing nucleophile, a carbon-containing nucleophile, a halogen-containing nucleophile, and an oxygen-containing nucleophile.

Preferred embodiments of the nitrogen-containing nucleophiles are described below.

According to a preferred embodiment of the present invention, the nitrogen-containing nucleophile is selected from at least one of azide salts, amides, sulfonamides, primary aliphatic amines, secondary aliphatic amines, primary aromatic amines, secondary aromatic amines and azaaromatic rings.

According to the invention, preferably, said azide salt is selected from NaN₃、TMSN₃At least one of (1).

According to the present invention, preferably, the amide is selected from at least one of formamide, acetamide, propionamide, succinimide, and phthalimide.

According to the invention, preferably, the sulphonamide is chosen from methanesulphonamide, benzenesulphonamide, p-toluenesulphonamide, di-p-toluenesulphonamideImides and

at least one of:

according to the present invention, preferably, the primary aliphatic amine is selected from at least one of n-propylamine, n-butylamine, n-pentylamine, n-hexylamine, benzylamine, 2-phenylethylamine, 3-phenylpropylamine, 4-phenylbutylamine.

According to the invention, the secondary aliphatic amine comprises a secondary acyclic or cyclic aliphatic amine, preferably selected from at least one of the following compounds:

according to the present invention, preferably, the primary aromatic amine is at least one selected from aniline, o-toluidine, m-toluidine, p-toluidine, o-chloroaniline, m-chloroaniline, p-chloroaniline, α -naphthylamine, and β -naphthylamine.

According to the present invention, preferably, the secondary aromatic amine is selected from at least one of N-methylaniline, N-methylbenzylamine, N-ethylaniline, diphenylamine, indoline, tetrahydroquinoline.

According to the present invention, preferably, the nitrogen heteroaromatic ring is selected from at least one of pyrazole, imidazole, oxazole, thiazole, triazole, benzopyrazole, benzimidazole, benzoxazole, benzothiazole, and benzotriazole.

More preferably, the nitrogen-containing nucleophile is selected from at least one of the following compounds:

NaN₃、

preferred embodiments of the sulfur-containing nucleophiles are described below.

According to a preferred embodiment of the present invention, the sulfur-containing nucleophile is selected from at least one of aliphatic thiols, substituted or unsubstituted thiophenolates, substituted or unsubstituted thiophenols, heteroarylthiols and sodium phenylsulfinate, and the substituents optionally present in the sulfur-containing nucleophile are each independently selected from at least one of halogen, alkyl, alkoxy, aryl, amine groups.

According to the present invention, preferably, the aliphatic thiol is selected from at least one of ethanethiol, propanethiol, n-butanethiol, benzylthiol, phenethylthiol, and phenylpropanethiol.

According to the present invention, preferably, the substituted or unsubstituted thiophenoxide is selected from at least one of sodium thiophenoxide, potassium thiophenoxide, lithium thiophenoxide, sodium 4-methylphenthiophenoxide.

According to the present invention, preferably, the substituted or unsubstituted thiophenol is selected from at least one of the following compounds:

according to the invention, preferably, the heteroaromatic thiol is selected from at least one of the following compounds:

more preferably, the sulfur-containing nucleophile is selected from at least one of the following compounds:

preferred embodiments of the oxygen-containing nucleophiles are described below.

Preferably, the oxygen-containing nucleophile is selected from at least one of a fatty carboxylate, a substituted or unsubstituted aromatic carboxylate, a substituted or unsubstituted alkyl alcohol, a substituted or unsubstituted alkyl alkoxide, a substituted or unsubstituted phenoxide, a substituted or unsubstituted phenol, and the substituents optionally present in the oxygen-containing nucleophile are each independently selected from at least one of a halogen, an alkoxy group, an alkyl group, an aryl group, an amine group.

According to the present invention, preferably, the fatty carboxylic acid salt is selected from at least one of sodium formate, sodium acetate, potassium acetate, sodium propionate, sodium phenylacetate, and sodium stearate.

According to the present invention, preferably, the substituted or unsubstituted aromatic carboxylic acid salt is selected from at least one of sodium benzoate and sodium 3, 5-difluorobenzoate.

According to the present invention, preferably, the substituted or unsubstituted alkyl alcohol is at least one selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, benzyl alcohol, allyl alcohol, propiolic alcohol, chloroethanol, bromoethanol, trifluoroethanol, ethylene glycol monomethyl ether, and ethylene glycol monoethyl ether.

According to the present invention, preferably, the substituted or unsubstituted alkyl alkoxide is selected from at least one of sodium methoxide, sodium ethoxide, and sodium propoxide.

According to the present invention, preferably, the substituted or unsubstituted phenate is selected from at least one of sodium phenolate, sodium o-nitrophenolate and sodium p-nitrophenolate.

According to the present invention, preferably, the substituted or unsubstituted phenol is at least one selected from the group consisting of phenol, o-cresol, m-cresol, p-cresol, o-chlorophenol, m-chlorophenol, p-chlorophenol, o-methoxyphenol, m-methoxyphenol, and p-methoxyphenol.

More preferably, the oxygen-containing nucleophile is selected from at least one of the following compounds:

preferably, the halogen-containing nucleophile is selected from at least one of sodium fluoride, potassium bifluoride, sodium chloride, potassium chloride, sodium bromide, potassium bromide, sodium iodide, potassium iodide.

Preferably, the carbon-containing nucleophile is selected from at least one of ethyl acetoacetate, malononitrile, diethyl propionate, ethyl cyanoacetate, 2, 4-pentanedione.

More preferably, the nucleophile is selected from at least one of a nitrogen-containing nucleophile, a sulfur-containing nucleophile, and an oxygen-containing nucleophile.

According to the present invention, preferably, in step (2), the molar ratio of the nucleophilic agent to the alcohol is 1 to 4: 1.

according to the present invention, preferably, in step (2), the conditions of the functionalization include: the temperature is from minus 20 ℃ to minus 160 ℃, and the time is 0.5 to 20 hours.

Preferably, the functionalization reaction is carried out in a protective atmosphere. According to the invention, the protective atmosphere is provided by at least one substance selected from nitrogen and an inert atmosphere.

Preferably, step (2) is carried out in the presence of a basic substance.

Preferably, the basic substance is at least one selected from potassium carbonate, sodium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, and potassium hydroxide.

Preferably, the basic substance is used in an amount of 0.5 to 2mmol relative to 1mmol of nucleophile.

Preferably, step (2) is carried out in the presence of a catalyst.

Preferably, the catalyst is Ag₂O。

Preferably, the catalyst is used in an amount of 1 to 5mmol relative to 1mmol of nucleophile.

Preferably, in step (2), the second solvent is selected from at least one of acetonitrile, N-Dimethylformamide (DMF), dimethylsulfoxide, dichloromethane, trichloromethane, dichloroethane, dioxane. More preferably acetonitrile or N, N-dimethylformamide.

Preferably, in the step (2), the second solvent is used in an amount of 2 to 20mL with respect to 1mmol of the alcohol.

Several preferred embodiments are provided below in accordance with the method of the present invention.

Detailed description of the preferred embodiment 1

The functionalization is amination and the nucleophile is a nitrogen-containing nucleophile, the method comprising:

(2) functionalizing the iodo intermediate in a second solvent in the presence of a nitrogen-containing nucleophile.

Preferably, the activator is trimethyliodosilane.

Preferably, the nitrogen-containing nucleophile is selected from at least one of an azide salt, an amide, a sulfonamide, a primary aliphatic amine, a secondary acyclic or cyclic aliphatic amine, a primary aromatic amine, a secondary aromatic amine, and an azaaromatic ring.

Preferably, the amination functionalization is represented by the following formula (2):

wherein, in the formula (2), R¹And R²And the aforementioned R¹And R²The definitions are correspondingly the same;

R³and R⁴Each independently selected from at least one of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted phenyl, acyl, sulfonyl, or R³、R⁴With N atoms forming a cyclic aliphatic amine or R³、R⁴And N atoms are combined to form nitrogen heterocyclic aromatic ring, and the optional substituent is selected from at least one of halogen, alkyl, alkoxy, aryl and amine.

According to a preferred embodiment of the invention:

the nitrogen-containing nucleophilic reagent is azide salt; the second solvent is DMF and the functionalizing conditions comprise: the temperature is 20-60 ℃, and the time is 2-16 h.

According to another preferred embodiment of the invention:

the nitrogen-containing nucleophile is selected from at least one of a primary aliphatic amine, a secondary (acyclic or cyclic) aliphatic amine, a primary aromatic amine, a secondary aromatic amine, and an azaaromatic ring; the second solvent is acetonitrile, and the functionalizing conditions comprise: heating and refluxing at 20-100 deg.C for 0.5-20 hr.

According to a further preferred embodiment of the invention:

the iodide intermediate is a chiral iodide, the nitrogen-containing nucleophile is azide, the amination product is a chiral azide product, and the chiral azide product and the iodide intermediate have opposite optical configurations, that is, when the alcohol is chiral alcohol and the nitrogen-containing nucleophile is azide, the optical configuration of the amination product maintains the optical configuration of the alcohol (chiral alcohol).

Detailed description of the preferred embodiment 2

The functionalization is sulfurization, and the nucleophile is a sulfur-containing nucleophile, the method comprising:

(2) functionalizing the iodo intermediate in a second solvent in the presence of a sulfur-containing nucleophile.

Preferably, the activator is trimethyliodosilane.

Preferably, the sulfur-containing nucleophile is selected from at least one of an aliphatic thiol, a substituted or unsubstituted thiophenolate, a substituted or unsubstituted thiophenol, a heteroaromatic thiol, and sodium phenyl sulfinate, and the optionally present substituents are selected from at least one of a halogen, an alkyl group, an alkoxy group, an aryl group, and an amine group.

Preferably, the sulfurization-functionalization reaction is represented by the following formula (3):

wherein, in the formula (3), R¹And R²And the aforementioned R¹And R²Define corresponding phasesThe same is carried out;

R⁵is selected from alkyl, substituted or unsubstituted phenyl and heteroaryl, and the optional substituent is selected from at least one of halogen, alkyl, alkoxy, aryl and amine.

According to a preferred embodiment of the invention:

the sulfur-containing nucleophile is substituted or unsubstituted thiophenolate and/or sodium phenylsulfinate, and step (2) comprises:

sulfurizing the iodo intermediate in a second solvent in the presence of a sulfur-containing nucleophile.

Preferably, the conditions of the vulcanization include: the temperature is 0-45 ℃ and the time is 0.5-8 h.

According to another preferred embodiment of the invention:

the sulfur-containing nucleophilic reagent is aliphatic thiol, substituted or unsubstituted thiophenol or heteroaromatic thiol, and the step (2) comprises the following steps:

sulfurizing the iodo intermediate in a second solvent in the presence of a sulfur-containing nucleophile and a basic substance.

According to a further preferred embodiment of the invention:

the iodide intermediate is a chiral iodide, the sulfur-containing nucleophile is substituted or unsubstituted thiophenol, the sulfuration reaction product is a chiral sulfuration product, and the optical configuration of the chiral sulfuration product is opposite to that of the iodide intermediate. That is, when the alcohol is a chiral alcohol and the sulfur-containing nucleophile is a substituted thiophenol, the optical configuration of the sulfuration reaction product maintains the optical configuration of the alcohol (chiral alcohol).

Detailed description of preferred embodiments 3

The functionalization is esterification and/or etherification, the nucleophile is an oxygen-containing nucleophile, the method comprising:

(2) functionalizing the iodo intermediate in a second solvent in the presence of an oxygen-containing nucleophile.

Preferably, the activator is trimethyliodosilane.

Preferably, the oxygen-containing nucleophile is selected from at least one of a fatty carboxylate, a substituted or unsubstituted aromatic carboxylate, a substituted or unsubstituted alkyl alcohol, a substituted or unsubstituted alkyl alkoxide, a substituted or unsubstituted phenoxide, a substituted or unsubstituted phenol, and the optionally present substituents are selected from at least one of a halogen, an alkoxy group, an alkyl group, an aryl group, and an amine group.

Preferably, the oxidative functionalization is represented by the following formula (4):

wherein, in the formula (4), R¹And R²And the aforementioned R¹And R²The definitions are correspondingly the same;

R⁶the aryl group is selected from substituted or unsubstituted alkyl, fatty acyl, substituted or unsubstituted benzoyl and substituted or unsubstituted phenyl, and the optional substituent is selected from at least one of halogen, alkoxy, alkyl, aryl and amine.

According to a preferred embodiment of the invention:

the oxygen-containing nucleophile is a fatty carboxylate and/or a substituted or unsubstituted aromatic carboxylate, the second solvent is DMF, step (2) comprises:

functionalizing the iodo intermediate in a second solvent in the presence of an oxygen-containing nucleophile.

According to a further preferred embodiment of the invention:

the oxygen-containing nucleophile is a substituted or unsubstituted phenol, the second solvent is acetonitrile, step (2) comprises:

functionalizing the iodo intermediate in a second solvent in the presence of an oxygen-containing nucleophile and a basic material.

Preferably, the alkaline substance is sodium carbonate.

According to a further preferred embodiment of the invention:

the oxygen-containing nucleophile is benzyl alcohol, the second solvent is acetonitrile, and step (2) comprises:

and in a second solvent, in the presence of an oxygen-containing nucleophilic reagent and a catalyst, carrying out a functionalization reaction on the iodide intermediate, wherein the functionalization reaction is an etherification reaction.

Preferably, the catalyst is Ag₂O。

According to the method, the reaction solution after the functionalization reaction is extracted, dried, separated and purified in sequence to obtain the alcohol functionalized substance. The method can realize the separation and purification of the functionalized substance through simple post-treatment operation.

Preferably, the conditions of the extraction include: the mixture was diluted with water, extracted with dichloromethane, and the organic solution was washed with saturated brine.

Preferably, the drying conditions include: drying with a drying agent, for example Na₂SO₄。

Preferably, the separation and purification are performed by a column chromatography method, and the conditions of the column chromatography comprise: 100-200 mesh silica gel is used, and petroleum ether and ethyl acetate are used as eluent.

According to the invention, in the step (2), iodine salt-containing by-products are generated, and the iodine salt-containing products can be removed by washing with water or recycled by an aqueous layer evaporation crystallization method.

In addition, the present invention may also include other post-treatment operation means conventional in the art, which is not particularly limited in this regard, and may be performed by using the operation existing in the art, and those skilled in the art should not be construed as limiting the present invention.

Compared with the classical Appel reaction and the Mitsunobu reaction, the invention provides the alcohol deoxidation functionalization method which is simple and convenient to operate and easy to purify, the product yield is high, the byproducts are few, the generated byproducts (such as silicon ether and iodized salt) can be removed and recycled through distillation or water washing, no acid waste is generated, and no harmful influence is caused to the environment.

In addition, the method has wider substrate application range, can select various nucleophiles, and can keep the optical configuration of the raw material alcohol by reacting with partial nucleophiles.

As previously mentioned, a second aspect of the invention provides an alcohol functional material selected from at least one of the following compounds:

as previously mentioned, a third aspect of the present invention provides a method of deoxygenating and activating an alcohol, the method comprising:

wherein, in the formula (I),

According to the process of the third aspect of the invention, R^a、R^b、R^cThe preferred embodiments of (1) and the aforementioned firstThe definitions of one aspect are the same, and are not described herein again.

According to the method of the third aspect of the present invention, the activator is at least one selected from the group consisting of trimethyl iodosilane, triethyl iodosilane, triisopropyl iodosilane, tri-n-butyl iodosilane, tri-t-butyl iodosilane, dimethyl-t-butyl iodosilane, tricyclohexyl iodosilane and triphenyl iodosilane, and more preferably trimethyl iodosilane.

According to the method of the third aspect of the present invention, the first solvent is at least one selected from the group consisting of dichloromethane, dichloroethane, chloroform, dioxane and acetonitrile, and more preferably dichloromethane.

According to the method of the third aspect of the present invention, the deoxidation activation conditions include: the temperature is from minus 20 ℃ to plus 100 ℃ and the time is 0.5 to 20 hours.

According to the process of the third aspect of the invention, the molar ratio of the activator to the alcohol is 1 to 4: 1.

according to a preferred embodiment of the present invention, the alcohol is a non-chiral alcohol, and the iodide intermediate obtained by deoxidation activation is a non-chiral iodide.

According to another preferred embodiment of the present invention, the alcohol is racemic alcohol, and the iodide intermediate obtained by deoxygenation activation is racemic iodide.

According to another preferred embodiment of the present invention, the alcohol is a chiral alcohol, the iodide intermediate obtained by deoxidation activation is a chiral iodide, and the optical configuration of the iodide is opposite to that of the alcohol.

In the third aspect of the present invention, the preferable conditions of the alcohol are the same as those of the first aspect, and the detailed description of the present invention is omitted here for avoiding redundancy.

With the process of the third aspect of the invention, the alcohol can be activated to give an iodide intermediate which can be used for subsequent further processing, such as functionalization (amination, sulfurization, esterification and etherification). Compared with the existing method for activating the alcohols, the method provided by the invention has high product yield, and the generated by-products (such as silyl ether) can be removed or recycled by distillation without influencing the subsequent functionalization reaction.

The present invention will be described in detail below by way of examples.

In the following examples, all the raw materials used are commercially available unless otherwise specified.

In the following examples, the specific structures of the compounds involved are shown in table 1, but the compounds synthesized by this method are not limited to the compounds of table 1.

In the following examples, reactions involving ee values of the products were compared using chiral alcohols as starting materials, and specific structures of the chiral products are shown in table 1, but the chiral compounds synthesized by this method are not limited to the chiral compounds in table 1.

In the following examples, reactions involving an ee value free of product all started with either an achiral or a racemic alcohol.

In the following examples, the procedures, conditions, reagents, experimental methods and the like of the present invention are all common knowledge in the art unless otherwise specified.

In the following examples, trimethylsilanol, hexamethyldisiloxane, sodium iodide, potassium iodide, ammonium iodide byproducts are produced and recycled by distillation or evaporative crystallization, but phosphine oxide-free byproducts and strong acid waste are not described in detail below.

In the following examples, the properties referred to were measured by the following methods:

(1) yield of

The yield is the actual produced weight of the target product/the theoretical produced weight of the target product × 100%.

(2) ee value (enantiomeric excess value)

The enantiomeric excess (absolute value of ee value) of the product of the invention is obtained by testing the chiral high performance liquid chromatography method and calculating according to the following formula.

ee value ═ R-S)/(R + S) × 100%

Wherein R and S are peak area ratios of corresponding peaks of an S-configuration product and an R-configuration product in a liquid chromatogram.

In the following examples, room temperature means 25. + -. 2 ℃ unless otherwise specified.

Example 1A

The structure of the preparation of compound III-1 is shown in Table 1.

(1) To an 8mL reaction flask, 0.2mmol of racemic 4-phenyl-2-butanol (I-1) and 1mL of dichloromethane were added as a solvent, and 0.4mmol of iodotrimethylsilane was added dropwise, and the mixture was reacted under argon atmosphere at room temperature with exclusion of light for 16 hours. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) to the iodo intermediate from step (1) was added 1mL of DMF and 0.4mmol of nitrogen-containing nucleophile (NaN)₃Formula N-1), reacting at 60 ℃ for 12 hours under the protection of argon. After the reaction was completed, water was added to quench, extract, dry, and after column chromatography, compound III-1 was obtained in 94% yield.

Nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.36–7.23(m,2H),7.23–7.12(m,3H),3.54–3.34(m,1H),2.83–2.57(m,2H),1.87–1.65(m,2H),1.26(d,J＝6.5Hz,3H).¹³C NMR(100MHz,CDCl₃)δ141.3,128.56,128.50,126.1,57.2,37.9,32.4,19.5.

example 1B

In a similar manner to example 1A, except that the amount of each reaction raw material was different, the kind was the same as in example 1A;

specifically, the method comprises the following steps: 0.2mmol of alcohol I-1, 0.2mmol of iodotrimethylsilane, and a nitrogen-containing nucleophile NaN₃0.4 mmol;

otherwise, the same procedure as in example 1A gave compound III-1 in a yield of 75%.

Example 1C

specifically, the method comprises the following steps: 0.2mmol of alcohol I-1, 0.4mmol of iodotrimethylsilane, and a nitrogen-containing nucleophile NaN₃0.2 mmol;

the remainder was the same as in example 1A, which gave compound III-1 in 83% yield.

Example 1D

In a similar manner to example 1A except that equal volume of dioxane was used in place of the dichloromethane in example 1A;

the remainder was the same as in example 1A, which gave compound III-1 in 80% yield.

Example 1E

In a similar manner to example 1A, except that an equimolar amount of triiodosilane was used instead of the triiodosilane of example 1A;

the remainder was the same as in example 1A, which gave compound III-1 in a yield of 52%.

Example 1F

In a similar manner to example 1A, except that the iodotrimethylsilane of example 1A was replaced with an equimolar amount of iodotriphenylsilane;

the remainder was the same as in example 1A, which gave compound III-1 in a yield of 35%.

Example 1G

In a similar manner to example 1A, except that the reaction starting alcohol was a chiral alcohol;

specifically, the method comprises the following steps: the alcohol was chiral (S) -4-phenyl-2-butanol (S-I-1), the remainder being the same as in example 1A.

The resulting iodide intermediate is chiral (R) -4-phenyl-2-iodobutane, which gives compound S-III-1 in 96% yield, 86% ee.

Example 2

The structure of the preparation of compound III-2 is shown in Table 1.

(1) 0.2mmol of alcohol I-1 and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, 0.4mmol of iodotrimethylsilane is added dropwise, and the mixture is reacted for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) 1mL of acetonitrile is added as a solvent, 0.4mmol of nitrogen-containing nucleophile (amine, N-2) is added, and the reaction is carried out for 12 hours at 60 ℃ under the protection of argon. After the reaction is completed, the mixture is extracted and washed by dichloromethane and saturated brine, and Na₂SO₄Drying, separating by column chromatography to obtain compound III-2 with 91% yield;

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.32–7.24(m,2H),7.22–7.12(m,3H),2.74–2.45(m,5H),1.84–1.72(m,1H),1.68–1.55(m,1H),1.53–1.40(m,2H),1.38–1.23(m,4H),1.10(d,J＝6.3Hz,3H),0.89(t,J＝5.8Hz,3H).¹³C NMR(100MHz,CDCl₃)δ142.4,128.3,125.7,52.8,47.3,38.7,32.4,30.1,29.6,22.6,20.4,14.1.

example 3

The structure of the compound III-3 is shown in Table 1.

(1) Alcohol I-1(0.2mmol) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, and trimethyl iodosilane (0.4mmol) is added dropwise and reacted for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) and (2) adding 1mL of acetonitrile serving as a solvent into the iodide intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-3), and reacting for 12 hours at 60 ℃ under the protection of argon. After the reaction is completed, the mixture is extracted and washed by dichloromethane and saturated brine, and Na₂SO₄Drying, separating by column chromatography to obtain compound III-3 with 94% yield;

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.31–7.22(m,2H),7.21–7.12(m,3H),2.78–2.66(m,1H),2.63–2.50(m,5H),2.40–2.27(m,1H),1.98–1.85(m,1H),1.83–1.70(m,4H),1.74–1.61(m,1H),1.15(d,J＝6.4Hz,3H).¹³C NMR(100MHz,CDCl₃)δ142.8,128.37,128.34,125.6,58.5,51.2,37.3,32.1,23.5,17.7.

example 4

The structure of the preparation of compound III-4 is shown in Table 1.

(1) 0.2mmol of alcohol (I-1) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, 0.4mmol of iodotrimethylsilane is added dropwise, and the mixture is reacted at room temperature under the protection of argon and in a dark place for 16 hours. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) adding 1mL of acetonitrile as a solvent, adding 0.4mmol of nitrogen-containing nucleophile (amine, N-4), and protecting with argonThe reaction was carried out at 60 ℃ for 12 hours. After the reaction is completed, the mixture is extracted and washed by dichloromethane and saturated brine, and Na₂SO₄Drying, separating by column chromatography to obtain compound III-4 with 93% yield;

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.29–7.22(m,2H),7.21–7.13(m,3H),3.75–3.64(m,4H),2.74–2.59(m,2H),2.58–2.48(m,3H),2.48–2.39(m,2H),1.90–1.79(m,1H),1.62–1.51(m,1H),1.00(d,J＝6.6Hz,3H).¹³C NMR(100MHz,CDCl₃)δ142.6,128.47,128.32,125.7,67.5,58.4,48.7,35.3,32.8,13.9.

example 5

Preparation of compound 5, the structure of which is shown in table 1.

(1) 0.2mmol of alcohol (I-1) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, 0.4mmol of iodotrimethylsilane is added dropwise, and the mixture is reacted at room temperature under the protection of argon and in the dark for 16 hours. After the reaction is completed, evaporating the solvent, and adding 1mL of acetonitrile as a solvent to obtain an iodo intermediate;

(2) and (2) adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-5) into the iodo intermediate obtained in the step (1), and reacting for 12 hours at 60 ℃ under the protection of argon. After the reaction is completed, the mixture is extracted and washed by dichloromethane and saturated brine, and Na₂SO₄Drying, separating by column chromatography to obtain compound III-5 with 91% yield;

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.50–7.25(m,10H),3.72(d,J＝13.4Hz,1H),3.57(d,J＝13.4Hz,1H),2.93–2.74(m,3H),2.27(s,3H),2.08–1.95(m,1H),1.77–1.65(m,1H),1.14(d,J＝6.5Hz,3H).¹³C NMR(100MHz,CDCl₃)δ143.0,140.5,128.81,128.57,128.39,128.29,126.7,125.7,57.61,57.19,36.52,36.13,33.2,13.3.

example 6

The structure of the preparation of compound III-6 is shown in Table 1.

(2) 1mL of acetonitrile is added as a solvent, 0.4mmol of nitrogen-containing nucleophile (amine, N-6) is added, and the reaction is performed under reflux at room temperature for 12 hours under the protection of argon. After the reaction is completed, the mixture is extracted and washed by dichloromethane and saturated brine, and Na₂SO₄Drying, separating by column chromatography to obtain compound III-6 with 93% yield;

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.31–7.26(m,2H),7.22–7.10(m,5H),6.70–6.63(m,1H),6.57–6.48(m,2H),3.49(h,J＝6.3Hz,1H),2.73(t,J＝7.9Hz,2H),1.88(dtd,J＝14.2,8.0,6.8Hz,1H),1.77(dtd,J＝13.9,7.9,6.2Hz,1H),1.55(s,1H),1.22(d,J＝6.3Hz,3H).¹³C NMR(100MHz,CDCl₃)δ147.5,141.9,129.2,128.43,128.38,125.8,116.9,113.1,47.8,38.8,32.4,20.8.

example 7

The structure of the preparation of compound III-7 is shown in Table 1.

(1) Alcohol I-1(0.2mmol) and 1mL dichloromethane serving as a solvent are added into an 8mL reaction bottle, and trimethyl iodosilane (0.4mmol) is added dropwise, and the reaction is carried out for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodide intermediate;

(2) and (3) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-7), and carrying out reflux reaction at room temperature for 12 hours under the protection of argon. After the reaction is completed, the mixture is extracted and washed by dichloromethane and saturated brine, and Na₂SO₄Drying, separating by column chromatography to obtain compound III-7 with 93% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.27–7.16(m,5H),7.15(d,J＝1.7Hz,2H),6.74(d,J＝7.8Hz,2H),6.68(t,J＝7.2Hz,1H),3.97–3.86(m,1H),2.75(s,3H),2.68–2.53(m,2H),1.99–1.89(m,1H),1.82–1.71(m,1H),1.12(d,J＝6.6Hz,3H).¹³C NMR(100MHz,CDCl₃)δ150.5,142.1,129.1,128.47,128.36,125.8,116.3,113.1,52.7,36.4,33.1,29.8,16.9.

example 8

The structure of the preparation of compound III-8 is shown in Table 1.

(2) and (3) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-8), and carrying out reflux reaction at room temperature for 12 hours under the protection of argon. After the reaction is completed, the mixture is extracted and washed by dichloromethane and saturated brine, and Na₂SO₄Drying, separating by column chromatography to obtain compound III-8 with 46% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.96(s,1H),7.88–7.79(m,1H),7.38–7.33(m,1H),7.31–7.27(m,3H),7.20(t,J＝7.2Hz,1H),7.08(d,J＝7.3Hz,2H),4.49–4.36(m,1H),2.62–2.47(m,2H),2.45–2.32(m,1H),2.26–2.13(m,1H),1.62(d,J＝6.8Hz,3H).¹³C NMR(100MHz,CDCl₃)δ144.1,141.0,140.3,133.2,128.59,128.35,126.3,122.72,122.13,120.5,110.2,51.4,37.8,32.3,21.1.

example 9

Preparation of Compound III-9, the Structure of which is shown in Table 1

(2) and (2) adding 1mL of acetonitrile serving as a solvent into the iodide intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-9), and carrying out reflux reaction for 12 hours at room temperature under the protection of argon. After the reaction is completed, the mixture is extracted and washed by dichloromethane and saturated brine, and Na₂SO₄Drying, separating by column chromatography to obtain compound III-9 with 29% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.57(d,J＝5.0Hz,1H),7.43(d,J＝12.8Hz,1H),7.30(t,J＝7.3Hz,2H),7.22(d,J＝7.2Hz,1H),7.16(d,J＝7.5Hz,2H),6.28(s,1H),4.43–4.28(m,1H),2.54–2.44(m,2H),2.38–2.25(m,1H),2.14–2.01(m,1H),1.54(d,J＝6.7Hz,3H).¹³C NMR(100MHz,CDCl₃)δ141.2,138.9,128.4,127.3,125.9,104.8,57.3,38.6,32.2,21.5.

example 10

Preparation of compound III-10, the structure is shown in Table 1.

(1) Alcohol I-2(0.2mmol) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, and trimethyl iodosilane (0.4mmol) is added dropwise and reacted for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodide intermediate;

(2) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), and adding K₂CO₃(0.4mmol), in this example alcohol I-2 as a nucleophile, was reacted at 60 ℃ for 12 hours under argon. After the reaction is completed, the mixture is extracted and washed by dichloromethane and saturated brine, and Na₂SO₄Drying, separating by column chromatography to obtain compound III-10 with 80% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.74(d,J＝8.0Hz,1H),7.36(d,J＝8.3Hz,2H),7.22(t,J＝7.7Hz,1H),7.15(d,J＝8.0Hz,2H),7.10(t,J＝7.5Hz,1H),6.97(d,J＝7.3Hz,1H),4.35(h,J＝6.5Hz,1H),2.36(s,4H),1.86–1.72(m,2H),1.38–1.30(m,1H),1.28(d,J＝6.5Hz,3H).¹³C NMR(100MHz,CDCl₃)δ143.3,136.3,135.1,133.4,129.4,127.98,127.52,127.02,126.6,125.5,52.2,30.0,24.6,21.65,21.54.

example 11

Preparation of compound III-11, the structure of which is shown in Table 1.

(1) Alcohol I-3(0.2mmol) and 1mL dichloromethane serving as a solvent are added into an 8mL reaction bottle, and trimethyl iodosilane (0.4mmol) is added dropwise, and the reaction is carried out for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) to the iodo intermediate from step (1) was added 1mL of DMF as solvent and 0.4mmol of nitrogen-containing nucleophile (NaN)₃) And reacting at 60 ℃ for 12 hours under the protection of argon. After the reaction is completed, water is added for quenching, extraction, drying and column chromatographic separation are carried out, and then the compound III-11 is obtained with the yield of 95 percent,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.35–7.29(m,2H),7.21–7.15(m,2H),7.15–7.09(m,1H),5.28(q,J＝7.1Hz,1H),2.09(d,J＝7.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ143.1,126.5,125.7,124.4,26.8,24.1.

example 12

Preparation of Compound III-12, the structure of which is shown in Table 1.

(1) Alcohol I-4(0.2mmol) and 1mL dichloromethane serving as a solvent are added into an 8mL reaction bottle, and trimethyl iodosilane (0.4mmol) is added dropwise, and the reaction is carried out for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) adding 1mL of DMF as a solvent to the iodo intermediate obtained in step (1), and adding 0.4mmol of nitrogen-containing nucleophile (NaN)₃N-1), reacting at 60 ℃ for 12 hours under the protection of argon. After the reaction is completed, water is added for quenching, extraction, drying and column chromatography separation are carried out, and the compound III-12 is obtained with the yield of 93 percent,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.45–7.36(m,3H),7.34(d,J＝7.2Hz,2H),4.35(s,2H).¹³C NMR(100MHz,CDCl₃)δ135.4,128.89,128.36,128.27,54.8.

example 13

Preparation of compound III-13, the structure is shown in Table 1.

(1) Alcohol I-4(0.2mmol) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, and trimethyl iodosilane (0.4mmol) is added dropwise and reacted for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) and (3) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-4), and reacting at 60 ℃ for 12 hours under the protection of argon. After the reaction is completed, dichloromethane and saturated saline are used for extraction washing, drying and column chromatography separation, and then the compound III-13 is obtained with the yield of 90 percent,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.36–7.27(m,4H),7.26–7.19(m,1H),3.69(t,J＝4.7Hz,4H),3.48(s,2H),2.42(t,J＝4.7Hz,4H).¹³C NMR(100MHz,CDCl₃)δ137.8,129.2,128.3,127.1,67.0,63.5,53.6.

example 14

Preparation of compound III-14, the structure of which is shown in Table 1.

(2) and (3) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-7), and carrying out reflux reaction at room temperature for 12 hours under the protection of argon. After the reaction was completed, the compound was extracted and washed with dichloromethane and saturated brine, dried, and separated by column chromatography to obtain the compound III-14 in 92% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.31–7.25(m,2H),7.23–7.16(m,5H),6.75–6.66(m,3H),4.49(s,2H),2.97(s,3H).¹³C NMR(100MHz,CDCl₃)δ149.8,139.1,129.3,128.7,127.0,126.8,116.6,112.5,56.7,38.6.

example 15

Preparation of compound III-15, the structure of which is shown in Table 1.

(1) Alcohol I-5(0.2mmol) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, and trimethyl iodosilane (0.4mmol) is added dropwise and reacted for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) to the iodo intermediate from step (1) was added 1mL of DMF as solvent and 0.4mmol of nitrogen-containing nucleophile (NaN)₃N-1), reacting at 60 ℃ for 12 hours under the protection of argon. After the reaction is completed, water is added for quenching, extraction, drying and column chromatographic separation are carried out, and then the compound III-15 is obtained with the yield of 94 percent,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.40(t,J＝7.3Hz,2H),7.35–7.27(m,3H),3.56(t,J＝7.3Hz,2H),2.96(t,J＝7.3Hz,2H).¹³C NMR(100MHz,CDCl₃)δ138.1,128.83,128.72,126.8,52.5,35.4.

example 16

Preparation of compound III-16, the structure of which is shown in Table 1.

(2) and (3) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-10), and reacting for 12 hours at 60 ℃ under the protection of argon. After the reaction was completed, the compound was extracted and washed with dichloromethane and saturated brine, dried, and separated by column chromatography to obtain compound III-16 in 58% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.37–7.27(m,4H),7.27–7.17(m,6H),2.95–2.87(m,2H),2.87–2.80(m,2H),2.72–2.57(m,4H),1.66(p,J＝8.3,7.7Hz,2H),1.55(p,J＝7.2Hz,2H),1.33(s,1H).¹³C NMR(100MHz,CDCl₃)δ142.4,140.1,128.74,128.49,128.43,128.29,126.1,125.7,51.2,49.7,36.4,35.8,29.77,29.21.

example 17

Preparation of compound III-17, the structure of which is shown in Table 1.

(2) and (3) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-3), and reacting at 60 ℃ for 12 hours under the protection of argon. After the reaction was completed, the compound was extracted and washed with dichloromethane and saturated brine, dried, and separated by column chromatography to obtain compound III-17 in 93% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.31–7.24(m,2H),7.24–7.15(m,4H),2.87–2.79(m,2H),2.72–2.63(m,2H),2.59–2.48(m,4H),1.85–1.74(m,4H).¹³C NMR(100MHz,CDCl₃)δ140.5,129.0,128.68,128.51,128.40,126.0,63.4,58.4,54.2,39.5,35.8,23.4.

example 18

Preparation of compound 18, the structure of which is shown in table 1.

(1) Alcohol I-5(0.2mmol) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, and trimethyl iodosilane (0.4mmol) is added dropwise and reacted for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodide intermediate;

(2) and (3) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-6), and carrying out reflux reaction at room temperature for 12 hours under the protection of argon. After the reaction was completed, the reaction mixture was extracted and washed with dichloromethane and saturated brine, dried, and subjected to column chromatography to obtain compound III-18 in 88% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.35–7.28(m,2H),7.24–7.14(m,5H),6.71(t,J＝7.2Hz,1H),6.61(d,J＝7.8Hz,2H),3.40(t,J＝7.0Hz,2H),2.91(t,J＝6.9Hz,2H).¹³C NMR(100MHz,CDCl₃)δ148.0,139.33,129.32,128.82,128.63,126.4,117.5,113.0,45.0,35.5.

example 19

Preparation of compound III-19, the structure is shown in Table 1.

(2) and (3) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), adding 0.4mmol of nitrogen-containing nucleophilic reagent (amine, N-7), and carrying out reflux reaction at room temperature for 12 hours under the protection of argon. After the reaction was completed, the compound was extracted and washed with dichloromethane and saturated brine, dried, and separated by column chromatography to obtain compound III-19 in 58% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.34–7.17(m,7H),6.77–6.67(m,3H),3.56(t,J＝7.6Hz,2H),2.88(s,3H),2.84(t,J＝7.6Hz,2H).¹³C NMR(100MHz,CDCl₃)δ148.8,139.8,129.3,128.86,128.58,126.2,116.2,112.1,54.8,38.5,32.9.

the following examples are presented to illustrate the preparation of the vulcanization reaction product.

Example 20

Preparation of compound 20, the structure of which is shown in table 1.

(2) to the iodo intermediate from step (1) was added 1mL acetonitrile as solvent, 0.4mmol sulfur-containing nucleophile (thiol, S-1) and K₂CO₃(0.4mmol) and reacted at room temperature under argon for 6 hours. After the reaction was completed, the compound was extracted and washed with dichloromethane and saturated brine, dried, and separated by column chromatography to obtain compound III-20 in 52% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.32–7.24(m,4H),7.23–7.15(m,6H),2.89–2.82(m,2H),2.81–2.65(m,5H),1.94–1.73(m,2H),1.31(d,J＝6.7Hz,3H).¹³C NMR(100MHz,CDCl₃)δ141.9,140.8,128.49,128.46,128.42,126.3,125.8,39.5,38.6,36.5,33.2,31.7,21.5.

example 21

Preparation of compound 21, the structure of which is shown in table 1.

(2) 1mL of DMF as a solvent was added to the iodo intermediate obtained in step (1), 0.4mmol of a sulfur-containing nucleophile (sodium thiophenolate, S-2) was added, and the reaction was carried out at room temperature under argon atmosphere for 6 hours. After the reaction is completed, dichloromethane and saturated saline are used for extraction washing, drying and column chromatography separation, and then the compound III-21 is obtained with the yield of 90 percent,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.38–7.32(m,2H),7.29–7.22(m,4H),7.22–7.14(m,4H),3.19(h,J＝6.7Hz,1H),2.83–2.72(m,2H),1.92(ddt,J＝13.6,9.0,6.7Hz,1H),1.81(ddt,J＝13.7,9.1,6.7Hz,1H),1.31(d,J＝6.7Hz,3H).¹³C NMR(100MHz,CDCl₃)δ141.7,135.1,132.0,128.88,128.54,128.47,126.8,125.9,42.5,38.2,33.2,21.2.

example 22A

Preparation of compound III-22, the structure of which is shown in Table 1.

(1) The chiral alcohol S-I-1(0.2mmol) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, and the trimethyl iodosilane (0.4mmol) is added dropwise and reacted for 16 hours at room temperature under the protection of argon and in a dark place. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) adding 1mL acetonitrile as solvent to the iodo intermediate obtained in step (1), adding 0.4mmol of sulfur-containing nucleophile (substituted thiophenol, S-3) and K₂CO₃(0.4mmol) and reacted at room temperature under argon for 6 hours. After the reaction was completed, the reaction mixture was washed with dichloromethane and saturated brine, dried, and subjected to column chromatography to obtain compound III-22 in 96% yield and 96% ee,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.31–7.24(m,3H),7.21–7.14(m,4H),7.14–7.08(m,2H),3.21(h,J＝6.7Hz,1H),2.86–2.72(m,2H),2.39(s,3H),1.97(ddt,J＝13.4,9.2,6.6Hz,1H),1.85(ddt,J＝13.7,9.1,6.7Hz,1H),1.32(d,J＝6.7Hz,3H).¹³C NMR(100MHz,CDCl₃)δ141.6,139.3,134.8,131.2,130.2,128.48,128.41,126.46,126.26,125.9,41.7,38.3,33.1,21.0,20.8.

example 22B

In a similar manner to example 22A except that an equal volume of dichloromethane was used as the solvent in place of acetonitrile in step (2) in example 22A;

the remainder was the same as in example 22A, which gave compound S-III-22 in 87% yield and 88% ee.

Example 22C

In a similar manner to example 22A, except that the room temperature reaction in step (2) in example 22A was replaced with refluxing at room temperature for 2 hours for 6 hours;

the remainder was the same as in example 22A, which gave compound S-III-22 in 95% yield and 25% ee.

Example 22D

In a similar manner to example 22A, except that an equimolar amount of racemic alcohol was used instead of the chiral alcohol in example 22A;

the remainder was the same as in example 22A, which gave racemic compound III-22 in a yield of 95%.

Example 23

Preparation of compound III-23, the structure is shown in Table 1.

(2) to the iodo intermediate from step (1) was added 1mL acetonitrile as solvent and 0.4mmol of sulfur-containing nucleophile (substituted thiophenol, S-4) and K₂CO₃(0.4mmol) and reacted at room temperature under argon for 6 hours. After the reaction was completed, the compound S-III-23 was obtained in 86% yield and 94% ee after extraction washing with dichloromethane and saturated brine, drying and column chromatography,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.25(d,J＝7.4Hz,5H),7.21–7.12(m,3H),7.08(d,J＝7.8Hz,2H),3.10(h,J＝6.7Hz,1H),2.85–2.69(m,2H),2.31(s,3H),1.96–1.83(m,1H),1.83–1.71(m,1H),1.28(d,J＝6.8Hz,3H).¹³C NMR(100MHz,CDCl₃)δ141.7,137.0,132.9,131.0,129.5,128.47,128.38,125.8,43.0,38.1,33.2,21.2,21.1.

example 24

Preparation of compound III-24, the structure of which is shown in Table 1.

(2) to the iodo intermediate from step (1) was added 1mL acetonitrile as solvent and 0.4mmol sulfur-containing nucleophile (substituted thiophenol, S-5) and K₂CO₃(0.4mmol)，The reaction was carried out at room temperature for 6 hours under the protection of argon. After the reaction is completed, dichloromethane and saturated saline are used for extraction washing, drying and column chromatography separation, the compound S-III-24 is obtained with 92% yield and 96% ee,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.47–7.38(m,2H),7.37–7.28(m,2H),7.28–7.17(m,3H),7.03(t,J＝8.4Hz,2H),3.13(h,J＝6.7Hz,1H),2.92–2.75(m,2H),2.04–1.75(m,2H),1.33(d,J＝6.8Hz,3H).¹³C NMR(100MHz,CDCl₃)δ162.3(d,J＝247.3Hz),141.6,135.1(d,J＝8.1Hz),129.6(d,J＝3.4Hz),128.4,125.9,115.9(d,J＝21.7Hz),43.5,38.0,33.1,21.1.

example 25

Preparation of compound III-25, the structure of which is shown in Table 1.

(2) to the iodo intermediate from step (1) was added 1mL acetonitrile as solvent and 0.4mmol sulfur-containing nucleophile (substituted thiophenol, S-6) and K₂CO₃(0.4mmol) and reacted at room temperature under argon for 6 hours. After the reaction was completed, the compound S-III-25 was obtained in 91% yield and 96% ee after extraction washing with dichloromethane and saturated brine, drying and column chromatography,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.31–7.18(m,7H),7.18–7.13(m,2H),3.15(h,J＝6.7Hz,1H),2.85–2.69(m,2H),1.91(ddt,J＝13.4,9.0,6.6Hz,1H),1.81(ddt,J＝13.8,9.0,6.7Hz,1H),1.30(d,J＝6.7Hz,3H).¹³C NMR(100MHz,CDCl₃)δ141.4,133.63,133.32,132.8,128.97,128.46,126.0,42.7,38.1,33.1,21.0.

example 26

Preparation of compound III-26, the structure of which is shown in Table 1.

(1) The chiral alcohol S-I-1(0.2mmol) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, and the trimethyl iodosilane (0.4mmol) is added dropwise and reacted for 16 hours at room temperature under the protection of argon and in a dark place. After the reaction is completed, evaporating the solvent to obtain an iodide intermediate;

(2) to the iodo intermediate from step (1) was added 1mL acetonitrile as solvent and 0.4mmol sulfur-containing nucleophile (substituted thiophenol, S-7) and K₂CO₃(0.4mmol) and reacted at room temperature under argon for 6 hours. After the reaction is completed, dichloromethane and saturated saline are used for extraction washing, drying and column chromatography separation, the compound S-III-26 is obtained with the yield of 90 percent and the ee of 98 percent,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.41(d,J＝8.5Hz,2H),7.35–7.27(m,3H),7.25–7.16(m,4H),3.19(h,J＝6.7Hz,1H),2.89–2.72(m,2H),1.94(ddt,J＝13.5,8.9,6.6Hz,1H),1.84(ddt,J＝13.6,8.7,6.7Hz,1H),1.34(d,J＝6.7Hz,3H).¹³C NMR(100MHz,CDCl₃)δ141.4,134.3,133.4,132.5,131.8,128.4,126.0,120.7,42.6,38.1,33.1,21.0.

example 27

Preparation of compound III-27, the structure of which is shown in Table 1.

(2) adding 1mL of acetonitrile serving as a solvent into the iodo intermediate obtained in the step (1), and adding sulfur-containing nucleophilic reagent to replace thiophenol S-5(0.4mmol) and K₂CO₃(0.4mmol) and reacted at room temperature under argon for 6 hours. After the reaction was completed, the compound was extracted and washed with dichloromethane and saturated brine, dried, and separated by column chromatography to obtain compound III-27 in 91% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.29–7.18(m,7H),6.97–6.89(m,2H),4.02(s,2H).¹³C NMR(100MHz,CDCl₃)δ162.1(d,J＝246.6Hz),137.5,133.4(d,J＝8.1Hz),130.7(d,J＝3.3Hz),128.87,128.49,127.2,115.9(d,J＝21.9Hz),40.4.

example 28

Preparation of compound III-28, the structure is shown in Table 1.

(2) to the iodo intermediate from step (1) was added 1mL acetonitrile as solvent and 0.4mmol sulfur-containing nucleophile (substituted thiophenol, S-5) and K₂CO₃(0.4mmol) and reacted at room temperature under argon for 6 hours. After the reaction is completed, dichloromethane and saturated saline are used for extraction washing, drying and column chromatography separation, and then the compound III-28 is obtained with the yield of 90 percent,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.63–7.56(m,2H),7.56–7.50(m,2H),7.49–7.39(m,3H),7.28–7.20(m,2H),3.35(dd,J＝9.2,6.5Hz,2H),3.13(dd,J＝9.3,6.4Hz,2H).¹³C NMR(100MHz,CDCl₃)δ161.8(d,J＝246.3Hz),140.0,132.3(d,J＝7.8Hz),131.1(d,J＝3.4Hz),128.56,128.54,126.5,116.0(d,J＝21.9Hz),36.5,35.7.

example 29

Compound 29 was prepared and its structure is shown in table 1.

(1) Alcohol I-1(0.2mmol) and 1mL of dichloromethane are added into an 8mL reaction bottle as a solvent, and trimethyl iodosilane (0.4mmol) is added dropwise and reacted for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodide intermediate;

(2) adding 1mL acetonitrile as solvent to the iodide intermediate obtained in step (1), adding 0.4mmol sulfur-containing nucleophile (S-8) and K₂CO₃(0.4mmol) and reacted at room temperature under argon for 6 hours. After the reaction was completed, the reaction mixture was washed with dichloromethane and saturated brine, dried, and subjected to column chromatography to obtain compound III-29 in 88% yield,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.67–7.60(m,1H),7.49–7.42(m,1H),7.35–7.24(m,5H),7.23(d,J＝7.3Hz,3H),3.98(h,J＝6.8Hz,1H),2.94–2.78(m,2H),2.24–2.01(m,2H),1.62(d,J＝6.8Hz,3H).¹³C NMR(100MHz,CDCl₃)δ164.5,151.6,142.0,141.1,128.50,128.43,126.1,124.2,123.8,118.4,109.8,42.9,38.3,33.2,21.8.

example 30

Preparation of compound III-30, the structure of which is shown in Table 1.

(2) 1mL of DMF as a solvent was added to the iodo intermediate obtained in step (1), 0.4mmol of a sulfur-containing nucleophile (sodium benzenesulfonate, S-9) was added, and the reaction was carried out under argon at room temperature for 10 hours. After the reaction is completed, dichloromethane and saturated saline are used for extraction washing, drying and column chromatography separation, and the compound III-30 is obtained with the yield of 66 percent,

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.90–7.83(m,2H),7.70–7.64(m,1H),7.61–7.54(m,2H),7.33–7.26(m,2H),7.25–7.19(m,1H),7.16–7.10(m,2H),3.11–3.00(m,1H),2.90–2.79(m,1H),2.67–2.56(m,1H),2.40–2.28(m,1H),1.81–1.69(m,1H),1.34(d,J＝6.9Hz,3H).¹³C NMR(100MHz,CDCl₃)δ140.1,137.1,133.6,129.13,129.00,128.61,128.32,126.3,59.1,32.4,30.7,13.2.

the following examples are provided to illustrate the preparation of the oxidation reaction products of the present invention

Example 31

Preparation of compound III-31, the structure is shown in Table 1.

(1) Alcohol I-1(0.2mmol) and 1mL dichloromethane serving as a solvent are added into an 8mL reaction bottle, and trimethyl iodosilane (0.4mmol) is added dropwise, and the reaction is carried out for 16 hours at room temperature under the protection of argon and in the dark. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) 1mL of DMF as a solvent was added to the iodo intermediate obtained in step (1), 0.4mmol of oxygen-containing nucleophile (potassium acetate, O-1) was added, and the reaction was carried out under argon at room temperature for 12 hours. After the reaction is completed, dichloromethane and saturated saline are used for extraction washing, drying and column chromatography separation, and then the compound III-31 is obtained with the yield of 90%;

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.31–7.25(m,2H),7.22–7.15(m,3H),4.99–4.89(m,1H),2.72–2.56(m,2H),2.03(s,3H),1.99–1.88(m,1H),1.86–1.75(m,1H),1.25(d,J＝6.3Hz,3H).¹³C NMR(100MHz,CDCl₃)δ170.8,141.5,128.43,128.32,125.9,70.5,37.5,31.8,21.3,20.0.

example 32

The preparation of compound III-32, the structure of which is shown in Table 1.

(2) and (2) adding 1mL of DMF (dimethyl formamide) serving as a solvent into the iodide intermediate obtained in the step (1), adding 0.4mmol of oxygen-containing nucleophilic reagent (sodium benzoate, O-2), and reacting at room temperature for 12 hours under the protection of argon. After the reaction is completed, extracting and washing the product by using dichloromethane and saturated saline, drying the product, and obtaining a compound III-32 with the yield of 92% after column chromatography separation;

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ8.11(d,J＝7.4Hz,2H),7.61(t,J＝7.4Hz,1H),7.49(t,J＝7.6Hz,2H),7.37–7.30(m,2H),7.28–7.20(m,3H),5.31–5.20(m,1H),2.88–2.72(m,2H),2.23–2.10(m,1H),2.06–1.95(m,1H),1.44(d,J＝6.2Hz,3H).¹³C NMR(100MHz,CDCl₃)δ166.2,141.5,132.8,130.8,129.5,128.50,128.40,128.37,125.9,71.2,37.8,31.9,20.2.

example 33

Preparation of compound III-33, the structure is shown in Table 1.

(2) adding 1mL acetonitrile as solvent to the iodo intermediate obtained in step (1), adding 0.4mmol oxygen-containing nucleophile (formula O-3) and K₂CO₃(0.4mmol) and reacted at room temperature under argon for 12 hours. After the reaction was completed, methylene chloride and saturated common salt were usedWashing with water, drying, separating by column chromatography to obtain compound III-33 with 88% yield;

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.30–7.23(m,2H),7.20–7.14(m,3H),6.81(s,4H),4.28–4.16(m,1H),3.75(s,3H),2.85–2.67(m,2H),2.10–1.97(m,1H),1.90–1.80(m,1H),1.28(d,J＝6.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ153.9,152.1,141.9,128.53,128.42,125.8,117.4,114.7,74.0,55.7,38.3,31.8,19.8.

example 34

Preparation of compound III-34, the structure is shown in Table 1.

(1) Alcohol I-1(0.2mmol) and 1mL dichloromethane are added into an 8mL reaction bottle as a solvent, 0.4mmol iodotrimethylsilane is added dropwise, and the mixture is reacted at room temperature under the protection of argon and protected from light for 16 hours. After the reaction is completed, evaporating the solvent to obtain an iodo intermediate;

(2) to the iodo intermediate from step (1) was added 1mL acetonitrile as solvent, 0.4mmol oxygen containing nucleophile (benzyl alcohol, O-4) and 0.8mmol Ag₂And O, reacting for 14 hours at 70 ℃ under the protection of argon. After the reaction is completed, dichloromethane and saturated saline are used for extraction washing, drying and column chromatography separation, and then the compound III-34 is obtained with the yield of 61%;

nuclear magnetic data:¹H NMR(400MHz,CDCl₃)δ7.43–7.36(m,4H),7.35–7.29(m,3H),7.21(ddd,J＝7.6,5.3,1.7Hz,3H),4.62(d,J＝11.7Hz,1H),4.49(d,J＝11.7Hz,1H),3.63–3.52(m,1H),2.81(ddd,J＝13.7,9.9,5.6Hz,1H),2.70(ddd,J＝13.8,9.8,6.5Hz,1H),1.97(dddd,J＝13.8,9.8,7.3,5.6Hz,1H),1.80(dddd,J＝13.7,9.9,6.5,4.9Hz,1H),1.27(d,J＝6.1Hz,3H).¹³C NMR(100MHz,CDCl₃)δ142.4,139.0,128.46,128.38,128.35,127.72,127.47,125.7,74.1,70.3,38.4,31.8,19.6.

table 1: each example reaction raw material, product structural formula and yield

From the above, the invention provides an alcohol deoxidation functionalization method which is simple and convenient to operate and easy to purify, and the method has wider substrate application range and can use various nucleophiles. And, the configuration of the starting alcohol can be maintained by reaction with a portion of the nucleophile.

The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable way, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.

Claims

1. A method for deoxygenating a functionalization of an alcohol, the method comprising:

(1) in a first solvent, in the presence of an activating agent, carrying out deoxidation activation on alcohol to obtain an iodo intermediate;

(2) functionalizing the iodo intermediate in a second solvent in the presence of a nucleophile to obtain an alcohol-functionalized material;

wherein the activator has a structure represented by formula (I);

wherein, in the formula (I),

2. The process according to claim 1, wherein, in formula (I),

R^a、R^band R^cEach independently selected from substituted or unsubstituted C_1-20Alkyl, substituted or unsubstituted C_6-20And R is an aryl group of^a、R^bAnd R^cWherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine;

preferably, in the formula (I),

R^a、R^band R^cEach independently selected from substituted or unsubstituted C_1-10Alkyl, substituted or unsubstituted C_6-15And R is an aryl group of^a、R^bAnd R^cWherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine;

more preferably, the activator is at least one selected from the group consisting of trimethyliodosilane, triiodosilane, triisopropyliodosilane, tri-n-butyliodosilane, tri-tert-butyliodosilane, dimethyl-tert-butyliodosilane, tricyclohexyliodosilane, and triphenyliodosilane, and more preferably is trimethyliodosilane.

3. The method of claim 1 or 2, wherein the alcohol has a structure represented by formula (II) and the iodide intermediate has a structure represented by formula (II'):

in the formulae (II) and (II'),

R¹and R²Each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, and R¹And R²Wherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine;

preferably, in formula (II) and formula (II'),

R¹and R²Each independently selected from the group consisting of hydrogen, substituted or unsubstituted C_1-20Alkyl, substituted or unsubstituted C_6-20And R is an aryl group of¹And R²Wherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine;

more preferably, in formula (II) and formula (II'),

4. The process according to any one of claims 1 to 3, wherein in step (1), the molar ratio of the activator to the alcohol is from 1 to 4: 1;

preferably, in step (1), the deoxidation activation conditions include: the temperature is from minus 20 ℃ to plus 100 ℃, and the time is 0.5 to 20 hours;

preferably, in step (1), the alcohol is a chiral alcohol, the iodide intermediate is a chiral iodide, and the iodide intermediate has an optical configuration opposite to that of the alcohol;

5. The process of any one of claims 1-4, wherein, in step (2), the functionalization is selected from at least one of amination, sulfurization, carbonization, halogenation, amidation, sulfonylamination, esterification, and etherification;

preferably, the functionalization is selected from at least one of amination, sulfurization, sulfonylamination, esterification, and etherification;

preferably, the nucleophile is selected from at least one of a nitrogen-containing nucleophile, a sulfur-containing nucleophile, a carbon-containing nucleophile, a halogen-containing nucleophile, and an oxygen-containing nucleophile;

more preferably, the nucleophile is selected from at least one of a nitrogen-containing nucleophile, a sulfur-containing nucleophile, and an oxygen-containing nucleophile;

preferably, the nitrogen-containing nucleophile is selected from at least one of azide salts, amides, sulfonamides, primary aliphatic amines, secondary aliphatic amines, primary aromatic amines, secondary aromatic amines, and azaaromatic rings;

preferably, the sulfur-containing nucleophile is selected from at least one of an aliphatic thiol, a substituted or unsubstituted thiophenolate, a substituted or unsubstituted thiophenol, a heteroaromatic thiol, and sodium phenyl sulfinate, and the substituents optionally present in the sulfur-containing nucleophile are each independently selected from at least one of a halogen, an alkyl group, an alkoxy group, an aryl group, an amine group;

6. The process according to any one of claims 1 to 5, wherein, in step (2), the molar ratio of the nucleophilic reagent to the alcohol is from 1 to 4: 1;

preferably, in step (2), the conditions of the functionalization comprise: the temperature is from minus 20 ℃ to minus 160 ℃, and the time is 0.5 to 20 hours.

7. The method of any one of claims 1-6, wherein the functionalization is amination and the nucleophile is a nitrogen-containing nucleophile, the method comprising:

(2) functionalizing said iodo intermediate in a second solvent in the presence of a nitrogen-containing nucleophile;

preferably, the alcohol is a chiral alcohol, the nitrogen-containing nucleophile is an azide salt, the amination reaction product is a chiral azide product, and the chiral azide product has the same optical configuration as the chiral alcohol.

8. The method of any one of claims 1-6, wherein the functionalization is sulfurization and the nucleophile is a sulfur-containing nucleophile, the method comprising:

(2) functionalizing said iodo intermediate in a second solvent in the presence of a sulfur-containing nucleophile;

preferably, the alcohol is a chiral alcohol and the sulfur-containing nucleophile is a substituted or unsubstituted thiophenol, the sulfuration reaction product is a chiral sulfuration product, and the chiral sulfuration product has the same optical configuration as the chiral alcohol.

9. The process according to any one of claims 1 to 6, wherein the functionalization is an esterification and/or etherification, the nucleophile is an oxygen-containing nucleophile, the process comprising:

10. An alcohol functionalized material, characterized in that the material is selected from at least one of the following compounds:

11. a method for deoxygenation activation of an alcohol, the method comprising:

wherein, in the formula (I),

12. The method according to claim 11, wherein, in formula (I),

R^a、R^band R^cEach independently selected from substituted or unsubstituted C_1-20Alkyl, substituted or unsubstituted C_6-20And is aryl ofR^a、R^bAnd R^cWherein the substituents optionally present are each independently selected from at least one of halogen, alkoxy, alkyl, aryl, heteroaryl, and amine;

preferably, in formula (I),

more preferably, the activator is at least one selected from the group consisting of trimethyliodosilane, triiodosilane, triisopropyliodosilane, tri-n-butyliodosilane, tri-t-butyliodosilane, dimethyl-t-butyliodosilane, tricyclohexyliodosilane, and triphenyliodosilane, and more preferably is trimethyliodosilane.

13. The process according to claim 11 or 12, wherein the molar ratio of the activator to the alcohol is from 1 to 4: 1;

preferably, the deoxygenation activation conditions include: the temperature is from minus 20 ℃ to plus 100 ℃, and the time is 0.5 to 20 hours;

preferably, the first solvent is selected from at least one of dichloromethane, dichloroethane, chloroform, dioxane, and acetonitrile, more preferably dichloromethane.