Olefin hydrocarbonylation method

Abstract

The invention provides an olefin hydrocarbonylation method which comprises the following step: olefin as shown in a formula (1), a nucleophilic reagent as shown in a formula (2) and carbon monoxide are subjected to a hydrocarbonylation reaction under the action of a metal catalyst, a ligand, protonic acid and optional iodide under the condition of illumination. According to the present invention, olefin represented by a formula (1), a nucleophilic reagent represented by a formula (2) and carbon monoxide are adopted as raw materials, and under the action of a metal catalyst, a ligand, a protonic acid and an optional iodide, a hydrocarbonylation reaction is performed under the illumination condition so as to obtain carboxylic acid / ester / amide / thioester and other products; the method provided by the invention can be realized at normal temperature and normal pressure, does not need special equipment, has low potential safety hazard and low energy consumption, greatly reduces the cost of large-scale production of carboxylic acid / ester / amide / thioester, and provides a novel green and efficient synthesis process for industrial production of carboxylic acid / ester / amide / thioester.

Description

Technical Field

[0001] The present invention relates to the technical field of organic chemistry, and in particular to a method for hydrocarbonylation of olefins. Background Art

[0002] Carboxylic acids and their derivatives, including compounds such as esters, amides, and thioesters, are widely used in a variety of fields, including materials, medicines, pesticides, fragrances, food additives, daily chemicals, and cosmetics. They are one of the most important categories of chemical production. For example, the chemical products containing carboxylic acids / esters / amides / thioesters shown below:

[0003]

[0004] With the development of the chemical industry, the annual output of such chemicals has exceeded tens of millions of tons. Therefore, it is very important to have a method for efficiently constructing carboxylic acids / esters / amides / thioesters. At present, the chemical methods for synthesizing carboxylic acids mainly include hydroformylation-oxidation, cyanidation-hydrolysis, halogenation-carbonylation, etc., while the synthesis of esters / amides / thioesters is generally achieved by synthesizing acid chlorides from carboxylic acids, and then undergoing substitution with nucleophiles such as alcohols / amines / thiols. However, these methods generally require multi-step synthesis, have low atom economy, and generate a lot of waste. The hydrocarbonylation reaction of olefins can directly synthesize products such as carboxylic acids / esters / amides / thioesters from simple olefins with carbon monoxide and nucleophiles such as water / alcohols / amines / thiols, with complete atom economy and excellent step economy.

[0005] Reppe first reported this type of hydrocarbonylation reaction in 1953. Using nickel tetracarbonyl as a catalyst, he used olefins, CO at 100-200 atm, and water / alcohols / amines / thiols to hydrocarbonylate carboxylic acids / esters / amides / thioesters at 200-300°C. However, due to the highly toxic nickel tetracarbonyl catalyst and the high reaction temperatures and pressures, the reaction was not commercially viable.

[0006]

[0007] In 1968, researchers at BASF reported a palladium-catalyzed olefin hydroesterification reaction system. Using bistriphenylphosphine palladium dichloride as a catalyst and hydrochloric acid as a protonic acid, the system hydroesterified olefins, CO at 300-700 atm, and ethanol at temperatures between 60°C and 140°C to produce esters. While this method significantly reduced the temperature, the extremely high CO pressure required specialized equipment and presented significant safety risks.

[0008]

[0009] In 1999, Tooze's group reported a method for synthesizing methyl propionate by hydrogenation of methanol using a highly efficient bisphosphine ligand, a palladium catalyst, methanesulfonic acid as a protonic acid, and a 10 atm mixture of ethylene and CO at 80°C. The TON exceeded 100,000.

[0010]

[0011] In 2015, Huang Hanmin's group reported the use of amine acetal as an amine source, palladium catalyst, and glycine methyl ester hydrochloride as a protonic acid to achieve the olefin hydroamine carbonylation reaction at a temperature of 120°C and a pressure of 10 atm CO. This method successfully overcomes the poisoning effect of aliphatic amines and allows the synthesis of a wide range of N-alkyl substituted amides under mild reaction conditions.

[0012]

[0013] In 2019, Beller's group reported a new type of bisphosphine ligand, using palladium catalyst, sulfuric acid as protonic acid, and aqueous acetic acid as solvent. At a temperature of 100°C, olefins, 40 bar CO and water hydrogen carboxylation were used to synthesize alkyl carboxylic acids with a TON exceeding 350,000.

[0014]

[0015] Although the above reaction achieves the hydrocarbonylation of olefins, it generally requires relatively high temperature and pressure, places high demands on special equipment, has great safety risks, and consumes a lot of energy. Summary of the Invention

[0016] In view of this, the purpose of the present application is to provide a method for the hydrocarbonylation of olefins. The method provided in the present application can be carried out at room temperature and pressure, and is universally applicable to different types of hydrocarbonylation reactions including hydrocarboxylation, hydroesterification, hydroamine carbonylation, and hydrothiocarbonylation.

[0017] The present application provides a method for the hydrocarbonylation of olefins, comprising the following steps:

[0018] The olefin represented by formula (1), the nucleophile represented by formula (2) and carbon monoxide undergo a hydrocarbonylation reaction under the action of a metal catalyst, a ligand, a protonic acid and an optional iodide under light conditions;

[0019]

[0020] In formula (1), R 1 、R 2 、R 3 With R 4independently selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, or a substituted or unsubstituted C1-C40 amide group; or R 1 、R 2 、R 3 With R 4 The adjacent groups are connected to form a substituted or unsubstituted C3-C40 alicyclic group, a substituted or unsubstituted C3-C40 heterocyclic group; R 1 、R 2 、R 3 With R 4 At least one of them is selected from hydrogen;

[0021] In formula (2), Nu is selected from hydroxyl, OR 5 NR 6 R 7 or SR 8 ;

[0022] R 5 Selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, a substituted or unsubstituted C1-C40 aldehyde group, a substituted or unsubstituted C2-C40 ketocarbonyl group, a substituted or unsubstituted C1-C40 alkylamino group, a substituted or unsubstituted C4-C60 aromaticamino group or a substituted or unsubstituted C1-C40 amide group;

[0023] R 6 、R 7 With R 8 independently selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, a substituted or unsubstituted C2-C40 ester group, a substituted or unsubstituted C1-C40 aldehyde group, a substituted or unsubstituted C2-C40 ketocarbonyl group, a substituted or unsubstituted C1-C40 alkylamino group, a substituted or unsubstituted C4-C60 aromaticamino group or a substituted or unsubstituted C1-C40 amide group; or, R 6 and R 7 Connected to the nitrogen where it is located to form a substituted or unsubstituted C2-C60 heterocyclic group;

[0024] The substituted substituent is selected from one or more of C1-C20 alkyl groups, C3-C20 cycloalkyl groups, C6-C20 aromatic groups, C4-C20 heterocyclic groups, C2-C20 ester groups, C2-C20 ketocarbonyl groups, C1-C20 amide groups, C1-C20 alkoxy groups, C4-C20 aromatic oxy groups, C2-C20 acyloxy groups, halogen groups, cyano groups, nitro groups, sulfonic acid groups, phosphate groups and amino groups.

[0025] The present application uses an olefin represented by formula (1), a nucleophile represented by formula (2), and carbon monoxide as raw materials, and carries out a hydrocarbonylation reaction under the action of a metal catalyst, a ligand, a protonic acid, and an optional iodide under light conditions to obtain products such as carboxylic acids / esters / amides / thioesters. The method provided in the present application can be implemented at room temperature and pressure, does not require special equipment, has low safety risks, consumes less energy, greatly reduces the cost of large-scale production of carboxylic acids / esters / amides / thioesters, and provides a new green and efficient synthesis process for their industrial production.

[0026] The present application uses the olefin represented by formula (1) as raw material, wherein R 1 、R 2 、R 3 With R 4 independently selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, or a substituted or unsubstituted C1-C40 amide group; or R 1 、R 2 、R 3 With R 4 The adjacent groups are connected to form a substituted or unsubstituted C3-C40 alicyclic group, a substituted or unsubstituted C3-C40 heterocyclic group; R 1 、R 2 、R 3 With R 4 At least one of them is selected from hydrogen.

[0027] In some specific implementations, R 1 、R 2 、R 3 With R 4 At least two of them are selected from hydrogen.

[0028] In some specific implementations, R 1 、R 2 、R 3 With R 4Each is independently hydrogen, a substituted or unsubstituted C1-C30 aliphatic group, a substituted or unsubstituted C4-C30 aromatic group, a substituted or unsubstituted C4-C30 heterocyclic group, or a substituted or unsubstituted C1-C20 amide group. Or R 1 、R 2 、R 3 With R 4 Adjacent groups are connected to form a substituted or unsubstituted C3-C20 alicyclic group or a substituted or unsubstituted C3-C20 heterocyclic group.

[0029] In some specific implementations, R 1 、R 2 、R 3 With R 4 Each is independently hydrogen, a substituted or unsubstituted C1-C20 aliphatic group, a substituted or unsubstituted C4-C20 aromatic group, or a substituted or unsubstituted C4-C20 heterocyclic group. 1 、R 2 、R 3 With R 4 Adjacent groups are connected to form a substituted or unsubstituted C3~C10 alicyclic group or a substituted or unsubstituted C3~C10 heterocyclic group.

[0030] In some specific implementations, the substituted substituents include but are not limited to C1-C20 alkyl groups, C3-C20 cycloalkyl groups, C6-C20 aromatic groups, C4-C20 heterocyclic groups, C2-C20 ester groups, C2-C20 ketone carbonyl groups, C1-C20 amide groups, C1-C20 alkoxy groups, C4-C20 aromatic oxy groups, C2-C20 acyloxy groups, halogen groups, cyano groups, nitro groups, sulfonic acid groups, phosphate groups and amino groups, and can be one or more of them. In some specific implementations, the substituted substituent is selected from one or more of C1-C10 alkyl groups, C3-C10 cycloalkyl groups, C6-C10 aromatic groups, C4-C10 heterocyclic groups, C2-C10 ester groups, C2-C10 keto carbonyl groups, C1-C10 amide groups, C1-C10 alkoxy groups, C4-C10 aromatic oxy groups, C2-C10 acyloxy groups, halogen groups, cyano groups, nitro groups, sulfonic acid groups, phosphate groups and amine groups.

[0031] In some specific implementations, the substituted substituent is selected from one or more of methyl, ethyl, propyl, methoxy, C3-C6 cycloalkyl, phenyl, furyl, pyridyl, thienyl, pyrrolyl, indolyl, carbazolyl, acetyl, benzoyl, methoxyacyl, ethoxyacyl, ethoxy, propoxy, phenoxy, acetoxy, benzoyloxy, halogen, cyano, nitro, sulfonic acid, phosphate and amine.

[0032] It will be understood by those skilled in the art that, in the present application, the halogen is a halogen well known to those skilled in the art, without any special restrictions, and is preferably fluorine, chlorine or bromine; the heteroatom in the heterocyclic group is a heteroatom well known to those skilled in the art, without any special restrictions, and is preferably nitrogen, oxygen or sulfur.

[0033] In some specific implementations, R 1 、R 2 、R 3 With R 4 R is independently selected from hydrogen, phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, n-hexyl, tert-butyl, benzyl, 5-bromo-1-pentyl, 4-hydroxy-1-butyl, 3-oxo-1-phenylpropyl, 1-indolemethyl or perfluorobutyl. 1 and R 2 Connected to 3-phenylpentane, or, R 1 and R 2 Connected to butane.

[0034] The present application uses a nucleophilic reagent as a raw material, wherein Nu is selected from hydroxyl, OR 5 NR 6 R 7 or SR 8 ; R 5 R is selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, a substituted or unsubstituted C1-C40 aldehyde group, a substituted or unsubstituted C2-C40 ketocarbonyl group, a substituted or unsubstituted C1-C40 alkylamino group, a substituted or unsubstituted C4-C60 aromaticamino group or a substituted or unsubstituted C1-C40 amide group; 6 、R 7 With R 8 independently selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, a substituted or unsubstituted C2-C40 ester group, a substituted or unsubstituted C1-C40 aldehyde group, a substituted or unsubstituted C2-C40 ketocarbonyl group, a substituted or unsubstituted C1-C40 alkylamino group, a substituted or unsubstituted C4-C60 aromaticamino group or a substituted or unsubstituted C1-C40 amide group; or, R 6 and R 7 It is connected to the nitrogen where it is located to form a substituted or unsubstituted C2-C60 heterocyclic group.

[0035] In some specific implementations, R 5R is selected from hydrogen, a substituted or unsubstituted C1-C30 aliphatic group, a substituted or unsubstituted C4-C30 aromatic group, a substituted or unsubstituted C4-C30 heterocyclic group, a substituted or unsubstituted C1-C20 aldehyde group, a substituted or unsubstituted C2-C20 ketocarbonyl group, a substituted or unsubstituted C1-C20 alkylamino group, a substituted or unsubstituted C4-C30 aromaticamino group or a substituted or unsubstituted C1-C20 amide group; 6 、R 7 With R 8 are independently selected from hydrogen, a substituted or unsubstituted C1-C30 aliphatic group, a substituted or unsubstituted C4-C30 aromatic group, a substituted or unsubstituted C4-C30 heterocyclic group, a substituted or unsubstituted C2-C20 ester group, a substituted or unsubstituted C1-C20 aldehyde group, a substituted or unsubstituted C2-C20 ketocarbonyl group, a substituted or unsubstituted C1-C20 alkylamino group, a substituted or unsubstituted C4-C30 aromaticamino group or a substituted or unsubstituted C1-C20 amide group. Alternatively, R 6 and R 7 It is connected to the nitrogen where it is located to form a substituted or unsubstituted C2-C30 heterocyclic group.

[0036] In some specific implementations, R 5 R is selected from hydrogen, a substituted or unsubstituted C1-C20 aliphatic group, a substituted or unsubstituted C4-C20 aromatic group, a substituted or unsubstituted C4-C20 heterocyclic group, a substituted or unsubstituted C2-C10 ester group, a substituted or unsubstituted C1-C10 aldehyde group, a substituted or unsubstituted C2-C10 ketocarbonyl group, a substituted or unsubstituted C1-C10 alkylamino group, a substituted or unsubstituted C4-C20 aromaticamino group or a substituted or unsubstituted C1-C10 amide group; 6 、R 7 With R 8 are independently selected from hydrogen, a substituted or unsubstituted C1-C20 aliphatic group, a substituted or unsubstituted C4-C20 aromatic group, a substituted or unsubstituted C4-C20 heterocyclic group, a substituted or unsubstituted C2-C10 ester group, a substituted or unsubstituted C1-C10 aldehyde group, a substituted or unsubstituted C2-C10 ketocarbonyl group, a substituted or unsubstituted C1-C10 alkylamino group, a substituted or unsubstituted C4-C20 aromaticamino group or a substituted or unsubstituted C1-C10 amide group. Alternatively, R 6 and R 7 It is connected to the nitrogen where it is located to form a substituted or unsubstituted C3-C10 heterocyclic group.

[0037] In some specific implementations, R 5R is selected from hydrogen, a substituted or unsubstituted C1-C10 aliphatic group, a substituted or unsubstituted C4-C10 aromatic group, a substituted or unsubstituted C4-C10 heterocyclic group, a substituted or unsubstituted C2-C10 ester group, a substituted or unsubstituted C1-C10 aldehyde group, a substituted or unsubstituted C2-C10 ketocarbonyl group, a substituted or unsubstituted C1-C10 alkylamino group, a substituted or unsubstituted C4-C10 aromaticamino group or a substituted or unsubstituted C1-C10 amide group; 6 、R 7 With R 8 are independently selected from hydrogen, a substituted or unsubstituted C1-C10 aliphatic group, a substituted or unsubstituted C4-C10 aromatic group, a substituted or unsubstituted C4-C10 heterocyclic group, a substituted or unsubstituted C2-C10 ester group, a substituted or unsubstituted C1-C10 aldehyde group, a substituted or unsubstituted C2-C10 ketocarbonyl group, a substituted or unsubstituted C1-C10 alkylamino group, a substituted or unsubstituted C4-C10 aromaticamino group or a substituted or unsubstituted C1-C10 amide group. Alternatively, R 6 and R 7 It is connected to the nitrogen where it is located to form a substituted or unsubstituted C3-C10 heterocyclic group.

[0038] In some specific implementations, the substituted substituents include but are not limited to C1-C20 alkyl groups, C3-C20 cycloalkyl groups, C6-C20 aromatic groups, C4-C20 heterocyclic groups, C2-C20 ester groups, C2-C20 ketone carbonyl groups, C1-C20 amide groups, C1-C20 alkoxy groups, C4-C20 aromatic oxy groups, C2-C20 acyloxy groups, halogen groups, cyano groups, nitro groups, sulfonic acid groups, phosphate groups and amino groups, and can be one or more of them. In some specific implementations, the substituted substituent is selected from one or more of C1-C10 alkyl groups, C3-C10 cycloalkyl groups, C6-C10 aromatic groups, C4-C10 heterocyclic groups, C2-C10 ester groups, C2-C10 keto carbonyl groups, C1-C10 amide groups, C1-C10 alkoxy groups, C4-C10 aromatic oxy groups, C2-C10 acyloxy groups, halogen groups, cyano groups, nitro groups, sulfonic acid groups, phosphate groups and amine groups.

[0039] In some specific implementations, the substituted substituent is selected from one or more of methyl, ethyl, propyl, methoxy, C3-C6 cycloalkyl, phenyl, furyl, pyridyl, thienyl, pyrrolyl, indolyl, carbazolyl, acetyl, benzoyl, methoxyacyl, ethoxyacyl, ethoxy, propoxy, phenoxy, acetoxy, benzoyloxy, halogen, cyano, nitro, sulfonic acid, phosphate and amine.

[0040] It will be understood by those skilled in the art that, in the present application, the halogen is a halogen well known to those skilled in the art, without any special restrictions, and is preferably fluorine, chlorine or bromine; the heteroatom in the heterocyclic group is a heteroatom well known to those skilled in the art, without any special restrictions, and is preferably nitrogen, oxygen or sulfur.

[0041] In some specific implementations, R 5 、R 6 、R 7 、R 8 are independently selected from hydrogen, methyl, n-butyl, phenyl, p-methylphenyl, benzyl, 3,7-dimethyl-6-ene-octyl, 10,13-dimethyl-17-oxohexadecahydro-1H-cyclopenta[a]phenanthrene-3-yl, 2-(2,6-dioxopiperidin-3-yl)-1-oxo-4-isoindolinyl, and the like. In a specific implementation, R 6 and R 7 It is connected to the N where it is located to form 1,2,3,4-tetrahydroquinoline.

[0042] The present application uses carbon monoxide as a raw material. The present application has no special limitation on the pressure of the carbon monoxide, which can be 1 atm to 50 atm, preferably 1 atm to 20 atm, more preferably 1 atm to 5 atm, and most preferably 1 atm.

[0043] In some specific implementations, the molar ratio of the olefin represented by formula (1) to the nucleophile represented by formula (2) is preferably 3:1 to 1:100, more preferably 1:1 to 1:100, more preferably 1:2 to 1:50, and even more preferably 1:5 to 1:20. When the nucleophile represented by formula (2) is water, the molar ratio of the olefin represented by formula (1) to the nucleophile represented by formula (2) is most preferably 1:20; when the nucleophile represented by formula (2) is an alcohol, the molar ratio of the olefin represented by formula (1) to the nucleophile represented by formula (2) is most preferably 1:5; when the nucleophile represented by formula (2) is an amine / thiol, the molar ratio of the olefin represented by formula (1) to the nucleophile represented by formula (2) is more preferably 3:1 to 1:5, more preferably 1:2 to 3:1, even more preferably 1:1 to 1:2, and most preferably 1:1.5.

[0044] The method provided in the present application is carried out under the action of a metal catalyst, a ligand, a protonic acid and an optional iodide, wherein the metal catalyst is a transition metal catalyst well known to those skilled in the art, without any special limitation, and is preferably a compound comprising one or more elements of cobalt, nickel, copper, ruthenium and palladium, including but not limited to nickel chloride, nickel bromide, nickel iodide, nickel acetate, nickel sulfate, nickel acetylacetonate, nickel nitrate, dicobalt octacarbonyl, cobalt chloride, cobalt bromide, cobalt acetylacetonate, cobalt nitrate, cupric chloride, cuprous chloride, cuprous bromide, copper bromide, Cuprous, cuprous iodide, cupric acetate, copper acetylacetonate, ruthenium trichloride, triruthenium dodecacarbonyl, (1,5-cyclooctadiene) ruthenium dichloride, palladium chloride, palladium bromide, palladium iodide, palladium-carbon, tetrakistriphenylphosphine palladium, tris(dibenzylideneacetone) dipalladium, palladium acetate, palladium acetylacetonate, (1,5-cyclooctadiene) palladium dichloride, (1,5-cyclooctadiene) palladium dibromide, allylpalladium chloride, bisacetonitrile palladium chloride, bisbenzonitrile palladium chloride and palladium trifluoroacetate, etc., can be one or more of them, preferably tris(dibenzylideneacetone) dipalladium.

[0045] In the present application, the ligand is preferably an organic phosphine ligand and / or a nitrogen-containing organic ligand, including but not limited to triphenylphosphine, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, 5-bisdiphenylphosphino-9,9-dimethylxanthene, 4,5-bis-di-tert-butylphosphino-9,9-dimethylxanthene, 4,5-dicyclohexylphosphino-9,9-dimethylxanthene, 4,6-bis(diphenylphosphino)phenazine, bis(2-diphenylphosphinophenyl)ether, bis(2-dicyclohexylphosphinophenyl)ether, 2,2'-bipyridine, 6,6'-dimethyl-2,2'-bipyridine, terpyridine and 1,10-phenanthroline, etc., which can be one or more thereof, preferably (2-diphenylphosphinophenyl)ether.

[0046] In the present application, the proton acid is any proton acid well known to those skilled in the art without any particular limitation, including but not limited to p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, trichloroacetic acid, adamantanecarboxylic acid, benzoic acid, acetic acid, camphorsulfonic acid, glycine, ammonium chloride, triethylamine hydrochloride, pyridine hydrochloride, N-methylpyrrolidone hydrochloride and N-methylpyrrolidone hydrobromide, etc., and can be one or more thereof, preferably p-toluenesulfonic acid.

[0047] In the present application, the iodide is an optional added substance, including but not limited to elemental iodine, hydroiodic acid, lithium iodide, sodium iodide, potassium iodide, zinc iodide, ammonium iodide, tetramethylammonium iodide, tetraethylammonium iodide, tetrabutylammonium iodide, trimethylphenylammonium iodide, choline iodide, methyl iodide, ethyl iodide, iodobenzene, and can be one or more thereof, preferably sodium iodide.

[0048] In some specific implementations, the molar ratio of the metal catalyst to the olefin is preferably 0.001:1 to 0.1:1, more preferably 0.03:1 to 0.08:1, further preferably 0.04:1 to 0.06:1, and most preferably 0.05:1.

[0049] In some specific implementations, the molar ratio of the metal catalyst to the ligand element in the ligand is preferably 1:1 to 1:5, more preferably 1:1.2 to 1:4, further preferably 1:1.5 to 1:3.5, and most preferably 1:3.

[0050] In some specific implementations, the molar ratio of the olefin to the protonic acid is 5 to 20:1, preferably 8 to 15:1.

[0051] In some specific implementations, the molar ratio of the olefin to the iodide is 10 to 30:1, preferably 15 to 25:1.

[0052] In the present application, an olefin represented by formula (1), a nucleophile represented by formula (2), a metal catalyst, a ligand, a protonic acid and an optional iodide are mixed in a reaction medium, carbon monoxide is introduced, and a hydrocarbonylation reaction is carried out under light conditions.

[0053] In some specific implementations, the reaction medium includes but is not limited to benzene, chlorobenzene, fluorobenzene, toluene, trifluorotoluene, xylene, mesitylene, anisole, 1,4-dioxane, tetrahydrofuran, acetonitrile, benzonitrile, acetone, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, ethylene glycol dimethyl ether, methyl tert-butyl ether, methyl cyclopentyl ether, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide, etc., and can be one or more of them, preferably 1,4-dioxane.

[0054] In some specific implementations, the concentration of olefin in the reaction system is preferably 0.1 mol / mL to 0.5 mol / mL, more preferably 0.2 mol / mL to 0.4 mol / mL.

[0055] In some specific implementations, the wavelength of the light is preferably 380 nm to 525 nm, more preferably 400 nm to 500 nm, even more preferably 427 nm to 480 nm, and most preferably 455 nm. In some specific implementations, the power of the light is preferably 5 to 30 W, more preferably 10 to 25 W, and most preferably 15 W.

[0056] In some specific implementations, the reaction temperature is preferably 10°C to 150°C, more preferably 15°C to 100°C, more preferably 20°C to 60°C, and most preferably 25°C to 40°C. The reaction time is preferably 1 hour to 144 hours, more preferably 6 hours to 48 hours, more preferably 18 hours to 36 hours, more preferably 20 hours to 30 hours, and most preferably 24 hours. In some specific implementations, the reaction is carried out under stirring.

[0057] After the reaction is completed, the present application preferably performs column chromatography on the obtained reaction product to obtain the target product such as acid / ester / amide / thioester with high purity. In the present application, the mobile phase of the column chromatography is preferably n-hexane and ethyl acetate; the volume ratio of n-hexane to ethyl acetate is preferably (1-100):1, more preferably (1-20):1.

[0058] The present application uses an alkene shown in formula (1), a nucleophilic reagent shown in formula (2) and carbon monoxide as raw materials, and carries out a hydrocarbonylation reaction under the action of a metal catalyst, a ligand, a protonic acid and an optional iodide under the conditions of illumination to obtain products such as carboxylic acid / ester / amide / thioester. The method provided by the present application can be realized at room temperature and pressure, does not require special equipment, has low safety hazards, consumes less energy, greatly reduces the cost of large-scale production of carboxylic acid / ester / amide / thioester, and provides a green and efficient new synthesis process for its industrial production. At the same time, the method provided by the present application has universality for different types of hydrocarbonylation reactions including hydrocarboxylation, hydroesterification, hydroamine carbonylation, and hydrothiocarbonylation. BRIEF DESCRIPTION OF THE DRAWINGS

[0059] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the product prepared in Example 1;

[0060] Figure 2 The carbon NMR spectrum of the product prepared in Example 1 is shown. DETAILED DESCRIPTION

[0061] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0062] The present application provides a method for the hydrocarbonylation of olefins, comprising the following steps:

[0063] The olefin represented by formula (1), the nucleophile represented by formula (2) and carbon monoxide undergo a hydrocarbonylation reaction under the action of a metal catalyst, a ligand, a protonic acid and an optional iodide under light conditions;

[0064]

[0065] In formula (1), R 1 、R 2 、R 3 With R 4 independently selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, or a substituted or unsubstituted C1-C40 amide group; or R 1 、R 2 、R 3 With R 4 The adjacent groups are connected to form a substituted or unsubstituted C3-C40 alicyclic group, a substituted or unsubstituted C3-C40 heterocyclic group; R 1 、R 2 、R 3 With R 4 At least one of them is selected from hydrogen;

[0066] In formula (2), Nu is selected from hydroxyl, OR 5 NR 6 R 7 or SR 8 ;

[0067] R 5 Selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, a substituted or unsubstituted C1-C40 aldehyde group, a substituted or unsubstituted C2-C40 ketocarbonyl group, a substituted or unsubstituted C1-C40 alkylamino group, a substituted or unsubstituted C4-C60 aromaticamino group or a substituted or unsubstituted C1-C40 amide group;

[0068] R 6 、R 7 With R 8 independently selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, a substituted or unsubstituted C2-C40 ester group, a substituted or unsubstituted C1-C40 aldehyde group, a substituted or unsubstituted C2-C40 ketocarbonyl group, a substituted or unsubstituted C1-C40 alkylamino group, a substituted or unsubstituted C4-C60 aromaticamino group or a substituted or unsubstituted C1-C40 amide group; or, R 6 and R 7 Connected to the nitrogen where it is located to form a substituted or unsubstituted C2-C60 heterocyclic group;

[0069] The substituted substituent is selected from one or more of C1-C20 alkyl groups, C3-C20 cycloalkyl groups, C6-C20 aromatic groups, C4-C20 heterocyclic groups, C2-C20 ester groups, C2-C20 ketocarbonyl groups, C1-C20 amide groups, C1-C20 alkoxy groups, C4-C20 aromatic oxy groups, C2-C20 acyloxy groups, halogen groups, cyano groups, nitro groups, sulfonic acid groups, phosphate groups and amino groups.

[0070] The present application uses an olefin represented by formula (1), a nucleophile represented by formula (2), and carbon monoxide as raw materials, and carries out a hydrocarbonylation reaction under the action of a metal catalyst, a ligand, a protonic acid, and an optional iodide under light conditions to obtain products such as carboxylic acids / esters / amides / thioesters. The method provided in the present application can be implemented at room temperature and pressure, does not require special equipment, has low safety risks, consumes less energy, greatly reduces the cost of large-scale production of carboxylic acids / esters / amides / thioesters, and provides a new green and efficient synthesis process for their industrial production.

[0071] In order to further illustrate the present invention, the following examples are given below to provide a detailed description.

[0072] Example 1

[0073]

[0074] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 31.5 mg of triphenylphosphine, 41.6 mg of styrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 12.5 mg of ethyl iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under a 15W, 455nm LED light source. After the reaction, the carbon monoxide was released, and the target product, phenylpropionic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 12% yield, with a linear product / branched product ratio of >20:1 and a purity of 95%.

[0075] The phenylpropionic acid obtained in Example 1 was analyzed by nuclear magnetic resonance, and its nuclear magnetic resonance hydrogen spectrum was obtained as follows: Figure 1 As shown, the carbon NMR spectrum is obtained as Figure 2 As shown, the results were 1H NMR (400 MHz, CDCl3) δ11.6 (s, 1H), 7.2–7.1 (m, 2H), 7.1–7.0 (m, 3H), 2.8 (t, J=7.8 Hz, 2H), 2.5 (dd, J=8.5, 7.2 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ179.78, 140.27, 128.69, 128.40, 126.50, 35.78, 30.66.

[0076] Example 2

[0077]

[0078] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 34.7 mg of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 41.6 mg of styrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 12.5 mg of ethyl iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released and the target product, phenylpropionic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 63% yield, with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0079] The phenylpropionic acid obtained in Example 2 was analyzed by nuclear magnetic resonance, and the results were basically consistent with those in Example 1, indicating that they were the same product.

[0080] Example 3

[0081]

[0082] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 41.6 mg of styrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 12.5 mg of ethyl iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the target product, phenylpropionic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 97% yield, with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0083] The phenylpropionic acid obtained in Example 3 was analyzed by nuclear magnetic resonance, and the results were basically consistent with those in Example 1, indicating that they were the same product.

[0084] Example 4

[0085]

[0086] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 41.6 mg of styrene, 144.0 mg of water, 3.8 mg of methanesulfonic acid, 12.5 mg of iodoethane, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the target product, phenylpropionic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 69% yield, with a linear product / branched product ratio of >20:1 and a purity of 96%.

[0087] The phenylpropionic acid obtained in Example 4 was analyzed by nuclear magnetic resonance, and the results were basically consistent with those in Example 1, indicating that they were the same product.

[0088] Example 5

[0089]

[0090] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 41.6 mg of styrene, 144.0 mg of water, 2.4 mg of acetic acid, 12.5 mg of ethyl iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the target product, phenylpropionic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 67% yield, with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0091] The phenylpropionic acid obtained in Example 5 was analyzed by nuclear magnetic resonance, and the results were basically consistent with those in Example 1, indicating that they were the same product.

[0092] Example 6

[0093]

[0094] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 41.6 mg of styrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 11.4 mg of iodomethane, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the target product, phenylpropionic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 55% yield, with a linear product / branched product ratio of >20:1 and a purity of 96%.

[0095] The phenylpropionic acid obtained in Example 6 was analyzed by nuclear magnetic resonance, and the results were basically consistent with those in Example 1, indicating that they were the same product.

[0096] Example 7

[0097]

[0098] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 41.6 mg of styrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, 144.0 mg of water, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released and the product was purified by column chromatography (n-hexane:ethyl acetate = 5:1) to obtain the desired product, phenylpropionic acid, in an 88% yield, with a linear product / branched product ratio of >20:1 and a purity of 96%.

[0099] The phenylpropionic acid obtained in Example 7 was analyzed by nuclear magnetic resonance, and the results were basically consistent with those in Example 1, indicating that they were the same product.

[0100] Example 8

[0101]

[0102] 7.2 mg of palladium iodide, 32.3 mg of bis(2-diphenylphosphinophenyl)ether, 41.6 mg of styrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under a 15 W 455 nm LED light source. After the reaction, the carbon monoxide was released, and the target product, phenylpropionic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 17% yield, with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0103] The phenylpropionic acid obtained in Example 8 was analyzed by nuclear magnetic resonance, and the results were basically consistent with those in Example 1, indicating that they were the same product.

[0104] Example 9

[0105]

[0106] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 41.6 mg of styrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 144.0 mg of water, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred under irradiation with a 15W 455nm LED light source for 24 hours. After the reaction, the carbon monoxide was released, and the target product, phenylpropionic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in an 18% yield, with a linear product / branched product ratio of >4.3:1 and a purity of 96%.

[0107] The phenylpropionic acid obtained in Example 9 was analyzed by nuclear magnetic resonance, and the results were basically consistent with those in Example 1, indicating that they were the same product.

[0108] Example 10

[0109]

[0110] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 41.6 mg of styrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W, 525nm LED light source. After the reaction, the carbon monoxide was released, and the target product, phenylpropionic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 63% yield, with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0111] The phenylpropionic acid obtained in Example 10 was analyzed by nuclear magnetic resonance, and the results were basically consistent with those in Example 1, indicating that they were the same product.

[0112] Example 11

[0113]

[0114] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 47.2 mg of 4-methylstyrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the desired carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 77% yield, with a linear product / branched product ratio of >20:1 and a purity of 96%.

[0115] The carboxylic acid obtained in Example 11 was analyzed by nuclear magnetic resonance and the results were 1H NMR (400MHz, CDCl3) δ11.8 (s, 1H), 7.5-7.1 (m, 4H), 3.0 (t, J = 7.7Hz, 2H), 2.8 (t, J = 7.8Hz, 2H), 2.4 (s, 3H). 13 C NMR (101MHz, CDCl3) δ179.79,137.19,135.94,129.35,128.25,35.92,30.25,21.12.

[0116] Example 12

[0117]

[0118] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl)ether, 53.6 mg of 4-methoxystyrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the desired carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 66% yield, with a linear product / branched product ratio of >20:1 and a purity of 96%.

[0119] The carboxylic acid obtained in Example 12 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ10.3 (s, 1H), 7.1-7.1 (m, 2H), 6.8-6.8 (m, 2H), 3.8 (s, 3H), 2.9 (t, J = 7.7Hz, 2H), 2.6 (t, J = 7.8Hz, 2H). 13 C NMR (101MHz, CDCl3) δ179.35,158.13,132.31,129.29,113.99,55.27,36.00,29.77.

[0120] Example 13

[0121]

[0122] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl)ether, 55.4 mg of 4-chlorostyrene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the target carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 69% yield, with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0123] The carboxylic acid obtained in Example 14 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ11.1(s,1H),7.2(dd,J=8.5,2.5Hz,2H),7.1(dd,J=8.6,2.6Hz,2H),2.9(td,J=7.7,2.7Hz,2H),2.6(td,J=7.7,2.7Hz,2H). 13 C NMR (101MHz, CDCl3) δ179.09,138.58,132.19,129.70,128.69,35.47,29.89.

[0124] Example 14

[0125]

[0126] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 44.9 mg of 1-octene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under a 15W, 455nm LED light source. After the reaction, the carbon monoxide was released, and the target carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 75% yield, with a linear product / branched product ratio of 11:1 and a purity of 96%.

[0127] The carboxylic acid obtained in Example 14 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ11.6 (s, 1H), 2.3 (t, J = 7.5Hz, 2H), 1.6-1.5 (m, 2H), 1.3-1.2 (m, 10H), 0.8-0.8 (m, 3H). 13C NMR (101MHz, CDCl3) δ180.74,34.16,31.81,29.22,29.12,29.07,24.67,22.65,14.07.

[0128] Example 15

[0129]

[0130] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 47.1 mg of allylbenzene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the desired carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 63% yield, with a linear product / branched product ratio of 10:1 and a purity of 96%.

[0131] The carboxylic acid obtained in Example 15 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ11.83(s,1H),8.38(d,J=8.0Hz,1H),7.72-7.57(m,1H),7.49(d,J=7.9Hz,1H),7.45 (t,J=7.5Hz,1H),6.36(s,1H),3.60(t,J=6.1Hz,2H),2.72(t,J=7.1Hz,2H),1.94(td,J=6.8,4.4Hz,4H). 13 C NMR (101MHz, CDCl3) δ165.1,141.5,138.7,132.8,127.3,126.0,125.9,124.5,104.5,44.7,32.7,32.0,25.8.

[0132] Example 16

[0133]

[0134] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 70.81 mg of 7-bromo-1-heptene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were placed in a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the desired carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in an 81% yield, with a linear product / branched product ratio of 12:1 and a purity of 96%.

[0135] The carboxylic acid obtained in Example 16 was analyzed by nuclear magnetic resonance and the results were 1 H NMRδ11.8(s,1H),3.3(t,J=6.8Hz,2H),2.3(t,J=7.5Hz,2H),1.8-1.7(m,2H),1.6-1.5(m,2H),1.4-1.3(m,2H),1.3-1.2(m,4H). 13 C NMR δ180.60,34.06,33.92,32.69,28.82,28.39,27.94,24.51.

[0136] Example 17

[0137]

[0138] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 40.0 mg of 5-hexen-1-ol, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released, and the target carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 1:1) in a 90% yield with a linear product / branched product ratio of 15:1 and a purity of 96%.

[0139] The carboxylic acid obtained in Example 17 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ7.3-6.8(m,2H),3.6(t,J=6.6Hz,2H),2.3(q,J=7.7Hz,2H),1.7-1.5(m,4H),1.5-1.3(m,4H). 13 C NMR (101MHz, CDCl3) δ178.65, 62.48, 34.01, 32.13, 28.77, 25.33, 24.67.

[0140] Example 18

[0141]

[0142] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 62.8 mg of 1-(allyl)indole, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released and the target carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 1:1) in a 65% yield with a linear product / branched product ratio of 12:1 and a purity of 96%.

[0143] The carboxylic acid obtained in Example 18 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ11.5 (s, 1H), 7.6 (ddd, J=7.8, 2.4, 1.4Hz, 1H), 7.3-7.3 (m, 1H), 7.2 (tdt, J=8.3, 2.8, 1.3Hz, 1H), 7 .1-7.0(m,1H),7.0(dd,J=3.1,1.4Hz,1H),6.6-6.4(m,1H),4.0(t,J=6.9Hz,2H),2.3-2.1(m,2H),2.0(p,J=7.0Hz,2H). 13 C NMR (101MHz, CDCl3) δ179.78,136.08,128.87,128.02,121.83,121.27,119.66,109.53,101.61,45.24,31.09,25.22.

[0144] Example 19

[0145]

[0146] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 62.8 mg of 4,4,5,5,6,6,7,7,7-nonafluoroheptanoic acid, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released and the product was purified by column chromatography (n-hexane:ethyl acetate = 1:1) to obtain the desired carboxylic acid in a 71% yield, with a linear product / branched product ratio of >20:1 and a purity of 98%.

[0147] The carboxylic acid obtained in Example 19 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ11.9 (s, 1H), 2.7 (dd, J = 8.8, 6.8Hz, 2H), 2.6-2.4 (m, 2H). 13 C NMR (101MHz, CDCl3) δ177.8, 122.2-104.4 (m), 26.0 (t, J = 22.2Hz), 25.2 (t, J = 4.4Hz). 19 F NMR (376MHz, CDCl3) δ-81.5--81.6(m),-115.5(ddt,J=12.8,7.6,4.1Hz),-124.8(pq,J=9.6,6.2,5.2Hz),-126.4(tt,J=17.9,5.7Hz).

[0148] Example 20

[0149]

[0150] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 68.8 mg of (4-methylidenecyclohexyl)benzene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released and the desired carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 5:1) in a 93% yield with a linear product / branched product ratio of >20:1 and a purity of 98%.

[0151] The carboxylic acid obtained in Example 20 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ11.18(s,1H),8.00(dd,J=9.3,2.7Hz,1H),7.48(dd,J=8.7,5.1Hz,1H),7.37(td,J=8.5,2. 4Hz,1H),6.32(s,1H),2.69-2.56(m,2H),1.77-1.72(m,2H),1.44(dt,J=14.6,7.4Hz,2H),0.98(t,J=7.3Hz,3H). 13C NMR (101MHz, CDCl3) δ162.1, 159.7, 141.4, 135.4, 128.0 (J=7.1Hz), 121.6 (J=24.2Hz), 112.3 (J=23.2Hz), 103.52, 33.12, 30.54, 22.31, 13.95.

[0152] Example 21

[0153]

[0154] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl)ether, 32.8 mg of cyclohexene, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released and the desired product, carboxylic acid, was obtained by column chromatography (n-hexane:ethyl acetate = 20:1) in a 77% yield and 96% purity.

[0155] The carboxylic acid obtained in Example 21 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ11.8(s,1H),2.3(tt,J=11.2,3.7Hz,1H),2.0-1.9(m,2H),1.8(dp ,J=13.1,3.2,2.6Hz,2H),1.7-1.6(m,1H),1.5(qd,J=11.6,3.4Hz,2H),1.4-1.2(m,3H). 13 C NMR (101MHz, CDCl3) δ183.05, 42.97, 28.75, 25.68, 25.33.

[0156] Example 22

[0157]

[0158] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 87.2 mg of naringenone, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under a 15W, 455nm LED light source. After the reaction, the carbon monoxide was released, and the desired carboxylic acid was obtained by column chromatography (n-hexane:ethyl acetate = 2:1) in a 63% yield, with a linear product / branched product ratio of >20:1 and a purity of 96%.

[0159] The carboxylic acid obtained in Example 22 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ11.3 (s, 1H), 5.8 (d, J = 1.7Hz, 1H), 2.5-2.3 (m, 3H), 2.3-2.1 (m, 3H), 2.1-1.8 (m,4H),1.8-1.7(m,1H),1.2(ddt,J=16.2,12.8,6.0Hz,1H),1.1(d,J=2.2Hz,3H),1.0-0.9(m,7H). 13 C NMR (101MHz, CDCl3) δ200.37,178.60,178.55,171.70,124.40,124.37,42.60,41.84,41.03,40.42,40.39,39.31, 39.21,39.19,38.80,37.16,37.14,34.50,33.04,32.94,29.98,28.50,16.90,16.89,16.56,16.20,14.92,14.90.

[0160] Example 23

[0161]

[0162] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 64.0 mg of methanol, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were placed in a Young's tube, connected to a carbon monoxide balloon, and stirred under irradiation with a 15 W 455 nm LED light source for 36 hours. After the reaction, the carbon monoxide was vented and the target ester was obtained by column chromatography (n-hexane:ethyl acetate = 20:1) in a 78% yield. The linear product / branched product ratio was 20:1, with a purity of 96%.

[0163] The ester obtained in Example 23 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ7.8 (dd, J=5.5, 3.1Hz, 2H), 7.8-7.7 (m, 2H), 3.7 (t, J=7 .2Hz,2H),3.7(s,3H),2.3(t,J=7.5Hz,2H),1.8-1.6(m,4H),1.4-1.3(m,2H). 13CNMR(101MHz, CDCl3)(126MHz, CDCl3)δ173.82,168.24,133.84,132.03,123.06,51.41,37.65,33.74,28.19,26.27,24.38.

[0164] Example 24

[0165]

[0166] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 188.2 mg of phenol, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were placed in a Young's tube, connected to a carbon monoxide balloon, and stirred under irradiation with a 15W 455nm LED light source for 36 hours. After the reaction, the carbon monoxide was vented and the desired ester was obtained by column chromatography (n-hexane:ethyl acetate = 20:1) in a 56% yield, with a linear product / branched product ratio >20:1 and a purity of 96%.

[0167] The ester obtained in Example 24 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (500MHz, CDCl3) δ7.9-7.8(m,2H),7.7-7.7(m,2H),7.4(t,J=7.9Hz,2H),7.2(t,J=7.4Hz,1H ),7.1-7.0(m,2H),3.7(t,J=7.2Hz,2H),2.6(t,J=7.5Hz,2H),1.9-1.7(m,4H),1.5-1.4(m,2H). 13 C NMR (126MHz, CDCl3) δ172.03,168.47,150.67,133.96,132.11,129.42,125.76,123.27,123.23,121.59,37.76,34.17,28.31,26.33,24.47.

[0168] Example 25

[0169]

[0170] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl)ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 232.2 mg of epiandrosterone, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 36 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released and the target ester was obtained by column chromatography (n-hexane:ethyl acetate = 20:1) in a 66% yield with a linear product / branched product ratio >20:1 and a purity of 97%.

[0171] The ester obtained in Example 25 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (500MHz, CDCl3) δ7.9-7.8(m,2H),7.8-7.7(m,2H),4.7(tt,J=11.4,4. 9Hz,1H),3.7(t,J=7.2Hz,2H),2.5-2.4(m,1H),2.3(t,J=7.4Hz,2H),2.2-2 .0(m,1H),2.0-1.9(m,1H),1.8-1.8(m,3H),1.8-1.6(m,6H),1.6-1.4(m,4 H),1.4-1.1(m,9H),1.1-0.9(m,2H),0.9(d,J=6.6Hz,6H),0.8-0.7(m,1H). 13 C NMR (126MHz, CDCl3) δ172.95,168.29,133.86,132.05,123.11,54.22,53.52,51.28,47.70,44.57,37.72,36.64, 35.79,35.58,34.95,34.41,33.89,31.47,30.75,28.24,28.21,27.37,26.27,24.55,21.73,20.41,13.78,12.18.

[0172] Example 26

[0173]

[0174] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 125.0 mg of citronellol, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were placed in a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 36 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was vented and the desired ester was obtained by column chromatography (n-hexane:ethyl acetate = 20:1) in a 60% yield with a linear product / branched product ratio >20:1 and a purity of 96%.

[0175] The ester obtained in Example 26 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (500MHz, CDCl3) δ8.0-7.8(m,2H),7.8-7.7(m,2H),5.1(dddd,J=8.5,7.1,2.9,1.5Hz,1H),4.2-4.0(m,2H),3.7(t,J=7.3Hz,2H),2.3(t, J=7.5Hz,2H),2.1-1.9(m,2H),1.8-1.6(m,8H),1.6(d,J=1.4Hz,3H),1.6-1.5(m,1H),1.5-1.3(m,4H),1.2-1.1(m,1H),0.9(d,J=6.6Hz,3H). 13 C NMR (126MHz, CDCl3) δ173.57,168.36,133.88,132.09,131.26,124.57,123.18,123.15,62 .84,37.75,36.94,35.39,34.13,29.43,28.29,26.36,25.73,25.36,24.50,19.39,17.65.

[0176] Example 27

[0177]

[0178] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 55.9 mg of aniline, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released and the target product, the amide, was obtained by column chromatography (n-hexane:ethyl acetate = 2:1) in a 93% yield with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0179] The amide obtained in Example 27 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ8.0 (d, J=15.2Hz, 1H), 7.7 (tt, J=5.3, 3.1Hz, 2H), 7.6 (pd, J=3.7, 1.4Hz, 2H), 7.5-7.4 (m, 2H), 7. 3-7.1(m,3H),7.0(td,J=7.3,1.2Hz,1H),3.5(t,J=7.2Hz,2H),2.2(t,J=7.6Hz,2H),1.7-1.5(m,4H),1.3-1.2(m,2H). 13 C NMR(101MHz, CDCl3)(101MHz, CDCl3)δ171.66,168.50,138.17,134.00,132.00,128.88,124.11,123.19,120.03,37.71,37.29,28.30,26.38,25.08.

[0180] Example 28

[0181]

[0182] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 79.9 mg of 1,2,3,4-tetrahydroquinoline, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was vented and the target product, the amide, was obtained by column chromatography (n-hexane:ethyl acetate = 4:1) in a 94% yield with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0183] The amide obtained in Example 28 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (500MHz, CDCl3) δ7.9-7.8(m,2H),7.7(dd,J=5.5,3.0Hz,2H),7.3-7.0(m,4H),3.8(t,J=6.6Hz,2H),3.6( t,J=7.2Hz,2H),2.7(t,J=6.7Hz,2H),2.5(t,J=7.5Hz,2H),2.0-1.9(m,2H),1.8-1.6(m,4H),1.4-1.3(m,2H). 13C NMR (126MHz, CDCl3) δ172.55,168.29,139.09,133.86,132.06,132.02,128.45,126. 03,125.12,124.62,123.09,42.87,37.78,34.28,28.40,26.77,26.53,25.44,24.14.

[0184] Example 29

[0185]

[0186] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 64.3 mg of benzylamine, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 36 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was vented and the target product, the amide, was obtained by column chromatography (n-hexane:ethyl acetate = 1:1) in a 54% yield with a linear product / branched product ratio of >20:1 and a purity of 96%.

[0187] The amide obtained in Example 29 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (500MHz, CDCl3) δ7.9-7.8(m,2H),7.7-7.7(m,2H),7.3-7.3(m,2H),7.3-7.2(m,3H),6.1(t,J=5.8Hz ,1H),4.4(d,J=5.7Hz,2H),3.6(t,J=7.2Hz,2H),2.2(t,J=7.5Hz,2H),1.8-1.6(m,4H),1.5-1.3(m,2H). 13 C NMR (126MHz, CDCl3) δ172.69,168.42,138.44,133.92,132.09,128.65,127.75,127.40,123.16,43.51,37.73,36.39,28.30,26.46,25.17.

[0188] Example 30

[0189]

[0190] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 155.4 mg of lenalidomide, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was released and the target product, the amide, was obtained by column chromatography (n-hexane:ethyl acetate = 1:1) in an 88% yield, with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0191] The amide obtained in Example 30 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (400MHz, CDCl3) δ9.7(s,1H),7.9-7.7(m,5H),7.5-7.4(m,2H),5.7(s,3H),5.1(dd,J=13.2,5.1Hz,1H),4.4-4.2(m,2H),3.5(t,J=7.0H z,2H),2.9-2.8(m,1H),2.6-2.5(m,1H),2.3(h,J=9.7,8.9Hz,3H),2.0(ddd,J=11.1,5.5,3.3Hz,1H),1.6(t,J=7.6Hz,4H),1.3-1.2(m,2H). 13 C NMR (101MHz, CDCl3) δ178.12,176.44,176.31,173.18,173.06,139.58,138.96,138.92,137.86,136.78,133 .81,130.45,128.19,124.19,60.13,56.71,51.65,42.55,40.76,36.43,32.95,31.10,29.85,28.00,27.85.

[0192] Example 31

[0193]

[0194] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 54.1 mg of butanethiol, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were placed in a Young's tube, connected to a carbon monoxide balloon, and stirred for 24 hours under irradiation with a 15W 455nm LED light source. After the reaction, the carbon monoxide was vented and the target thioester was obtained by column chromatography (n-hexane:ethyl acetate = 1:1) in a 93% yield with a linear product / branched product ratio of >20:1 and a purity of 97%.

[0195] The thioester obtained in Example 31 was analyzed by nuclear magnetic resonance and the results were 1 H NMR (500MHz, CDCl3) δ7.9-7.8(m,2H),7.8-7.7(m,2H),3.7(t,J=7.3Hz,2H),2.8(t,J=7.4Hz,2H ),2.5(t,J=7.5Hz,2H),1.8-1.7(m,4H),1.6-1.5(m,2H),1.4-1.3(m,4H),0.9(t,J=7.3Hz,3H). 13 C NMR (101MHz, CDCl3) (126MHz, CDCl3) δ 199.28, 168.28, 133.85, 132.06, 123.11, 43.74, 37.65, 31.58, 28.45, 28.21, 26.11, 25.11, 21.90, 13.57.

[0196] Example 32

[0197]

[0198] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 86.0 mg of 2-(4-penten-1-yl)isoindoline-1,3-dione, 74.4 mg of p-methylthiophenol, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A carbon monoxide balloon was attached and the mixture was stirred for 24 hours under irradiation with a 15 W 455 nm LED light source. After the reaction, the carbon monoxide was released and the target thioester was obtained by column chromatography (n-hexane:ethyl acetate = 1:1) in an 82% yield with a linear product / branched product ratio of 15:1 and a purity of 97%.

[0199] The thioester obtained in Example 32 was analyzed by nuclear magnetic resonance and the results were 1H NMR (500MHz, CDCl3) δ7.9-7.8(m,2H),7.7-7.7(m,2H),7.3-7.2(m,2H),7.2(d,J=8.0Hz,2H ),3.7(t,J=7.2Hz,2H),2.6(t,J=7.4Hz,2H),2.4(s,3H),1.8-1.7(m,4H),1.5-1.4(m,2H). 13 C NMR (126MHz, CDCl3) δ197.79,168.41,139.58,134.46,133.94,132.09,130.01,124.28,123.20,43.26,37.71,28.28,26.17,25.09,21.36.

[0200] Example 33

[0201]

[0202] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl)ether, 144.0 mg of water, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were placed in a Young's tube. A mixture of ethylene and CO (1:2) was introduced and stirred for 24 hours under irradiation with a 15 W LED light source at a wavelength of 455 nm. After the reaction, carbon monoxide was released, and propionic acid represented by Formula (III) was analyzed by gas chromatography using n-tetradecane as an internal standard. The yield was 84%.

[0203] Example 34

[0204]

[0205] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl) ether, 97.2 mg of 3,4-dichloroaniline, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were added to a Young's tube. A mixture of ethylene and carbon monoxide (1:2) was introduced and stirred for 24 hours under irradiation with a 15W LED light source at a wavelength of 455 nm. After the reaction, carbon monoxide was released and the target herbicide, propanil, was obtained by column chromatography (n-hexane:ethyl acetate = 1:1) in an 89% yield, with a linear product / branched product ratio of 15:1 and a purity of 97%.

[0206] The herbicide propanil obtained in Example 34 was analyzed by nuclear magnetic resonance and the results were 1HNMR (400MHz, CDCl3) δ7.8-7.7(m,1H),7.4-7.3(m,2H),2.4(qd,J=7.5,2.5Hz,2H),1.3-1.2(m,3H). 13 C NMR (101MHz, CDCl3) δ172.10,137.40,132.66,130.48,127.30,121.42,118.90,30.69,9.49.

[0207] Example 35

[0208]

[0209] 9.1 mg of tris(dibenzylideneacetone)dipalladium, 32.3 mg of bis(2-diphenylphosphinophenyl)ether, 64.9 mg of 4-acetoxystyrene, 90.7 mg of methyl anthranilate, 7.6 mg of p-toluenesulfonic acid, 3.0 mg of sodium iodide, and 2 mL of 1,4-dioxane were placed in a Young's tube, connected to a carbon monoxide balloon, and stirred under irradiation with a 15W 455nm LED light source for 24 hours. After the reaction, the carbon monoxide was released, and the target product, the amide, was obtained by column chromatography (n-hexane:ethyl acetate = 5:1). Ethanol (5 mL) and a 10% wt. sodium hydroxide solution (5 mL) were added, and the mixture was refluxed for 12 hours. Extraction was performed three times with ethyl acetate, and vacuum concentration was performed to obtain the pharmaceutical dihydroavense alkaloid in 82% yield, with a linear product / branched product ratio of 15:1 and a purity of 97%.

[0210] The dihydroavenous alkaloids obtained in Example 35 were analyzed by nuclear magnetic resonance and the results were 1 HNMR (500MHz, DMSO) δ13.6(s,1H),11.1(d,J=8.4Hz,1H),9.1(s,1H),8.5(d,J=8.4Hz,1H),8.0(dd,J=7.9,1.8Hz,1H),7.6(td,J= 8.0,7.5,1.7Hz,1H),7.1(t,J=7.6Hz,1H),7.1-7.0(m,2H),6.7(dq,J=9.6,3.2Hz,2H),2.8(t,J=7.6Hz,2H),2.6(t,J=7.7Hz,2H). 13 CNMR (126MHz, DMSO) δ171.07,169.99,156.02,141.30,134.52,131.55,131.19,129.58,123.00,120.38,116.80,115.57,30.28.

[0211] As can be seen from the above examples, the method provided by this application, which uses nucleophilic reagents such as olefins, water / alcohols / amines / thiols and carbon monoxide at normal pressure as raw materials, and undergoes a hydrocarbonylation reaction under the combined action of a metal catalyst, a ligand, a protic acid, and an iodide under room temperature illumination to obtain products such as carboxylic acids / esters / amides / thioesters, has the characteristics of a simple system, high efficiency, and high atom economy and step economy. In this application, using this method as a key step, it can be synthesized into bulk industrial products represented by propionic acid, pesticides represented by propanil, and pharmaceuticals represented by dihydroavense alkaloids, verifying the practicality of this method.

[0212] The above description of the disclosed embodiments will enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is to be construed in the widest manner consistent with the principles and novel features disclosed herein.

Claims

1. A method for the hydrocarbonylation of olefins, characterized in that: The following steps are involved: The olefin represented by formula (1), the nucleophile represented by formula (2) and carbon monoxide undergo a hydrocarbonylation reaction under the action of a metal catalyst, a ligand, a protonic acid and an optional iodide under light conditions; In formula (1), R 1 、R 2 、R 3 With R 4 independently selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, or a substituted or unsubstituted C1-C40 amide group; or R 1 、R 2 、R 3 With R 4 The adjacent groups are connected to form a substituted or unsubstituted C3-C40 alicyclic group, a substituted or unsubstituted C3-C40 heterocyclic group; R 1 、R 2 、R 3 With R 4 At least one of them is selected from hydrogen; In formula (2), Nu is selected from hydroxyl, OR 5 NR 6 R 7 or SR 8 ; R 5 Selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, a substituted or unsubstituted C1-C40 aldehyde group, a substituted or unsubstituted C2-C40 ketocarbonyl group, a substituted or unsubstituted C1-C40 alkylamino group, a substituted or unsubstituted C4-C60 aromaticamino group or a substituted or unsubstituted C1-C40 amide group; R 6 、R 7 With R 8 independently selected from hydrogen, a substituted or unsubstituted C1-C60 aliphatic group, a substituted or unsubstituted C4-C60 aromatic group, a substituted or unsubstituted C4-C60 heterocyclic group, a substituted or unsubstituted C2-C40 ester group, a substituted or unsubstituted C1-C40 aldehyde group, a substituted or unsubstituted C2-C40 ketocarbonyl group, a substituted or unsubstituted C1-C40 alkylamino group, a substituted or unsubstituted C4-C60 aromaticamino group or a substituted or unsubstituted C1-C40 amide group; or, R 6 and R 7 Connected to the nitrogen where it is located to form a substituted or unsubstituted C2-C60 heterocyclic group; The substituted substituent is selected from one or more of C1-C20 alkyl groups, C3-C20 cycloalkyl groups, C6-C20 aromatic groups, C4-C20 heterocyclic groups, C2-C20 ester groups, C2-C20 ketocarbonyl groups, C1-C20 amide groups, C1-C20 alkoxy groups, C4-C20 aromatic oxy groups, C2-C20 acyloxy groups, halogen groups, cyano groups, nitro groups, sulfonic acid groups, phosphate groups and amino groups.

2. The method according to claim 1, characterized in that The pressure of the carbon monoxide is 1 atm to 50 atm; the temperature of the reaction is 10° C. to 150° C.; and the wavelength of the light is 380 nm to 525 nm.

3. The method according to claim 1, characterized in that The metal catalyst is a compound of one or more elements selected from cobalt, nickel, copper, ruthenium and palladium; The ligand is selected from one or more of an organic phosphine ligand and a nitrogen-containing organic ligand.

4. The method according to claim 3, characterized in that The metal catalyst is selected from one or more of nickel chloride, nickel bromide, nickel iodide, nickel acetate, nickel sulfate, nickel acetylacetonate, nickel nitrate, dicobalt octacarbonyl, cobalt chloride, cobalt bromide, cobalt acetylacetonate, cobalt nitrate, cupric chloride, cuprous chloride, cupric bromide, cuprous bromide, cuprous iodide, cupric acetate, copper acetylacetonate, ruthenium trichloride, triruthenium dodecacarbonyl, (1,5-cyclooctadiene) ruthenium dichloride, palladium chloride, palladium bromide, palladium iodide, palladium-carbon, tetrakistriphenylphosphine palladium, tris(dibenzylideneacetone) dipalladium, palladium acetate, palladium acetylacetonate, (1,5-cyclooctadiene) palladium dichloride, (1,5-cyclooctadiene) palladium dibromide, allylpalladium chloride, bisacetonitrile palladium chloride, bisbenzonitrile palladium chloride and palladium trifluoroacetate; The ligand is selected from one or more of triphenylphosphine, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,1'-binaphthyl-2,2'-bisdiphenylphosphine, 5-bisdiphenylphosphino-9,9-dimethylxanthene, 4,5-bis-di-tert-butylphosphino-9,9-dimethylxanthene, 4,5-dicyclohexylphosphino-9,9-dimethylxanthene, 4,6-bis(diphenylphosphino)phenazine, bis(2-diphenylphosphinophenyl)ether, bis(2-dicyclohexylphosphinophenyl)ether, 2,2'-bipyridine, 6,6'-dimethyl-2,2'-bipyridine, terpyridine and 1,10-phenanthroline.

5. The method according to claim 1, wherein The protonic acid is selected from one or more of p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, trichloroacetic acid, adamantanecarboxylic acid, benzoic acid, acetic acid, camphorsulfonic acid, glycine, ammonium chloride, triethylamine hydrochloride, pyridine hydrochloride, N-methylpyrrolidone hydrochloride and N-methylpyrrolidone hydrobromide.

6. The method according to claim 1, characterized in that The iodide is selected from one or more of elemental iodine, hydroiodic acid, lithium iodide, sodium iodide, potassium iodide, zinc iodide, ammonium iodide, tetramethylammonium iodide, tetraethylammonium iodide, tetrabutylammonium iodide, trimethylphenylammonium iodide, choline iodide, methyl iodide, ethyl iodide or iodobenzene.

7. The method according to claim 1, characterized in that The molar ratio of the olefin to the nucleophile is 3:1 to 1:100; The molar ratio of the metal catalyst to the olefin is 0.001:1 to 0.1:1; The molar ratio of the metal catalyst to the ligand element in the ligand is 1:1 to 1:5; The molar ratio of the olefin to the protonic acid is 5 to 20:1; The molar ratio of the olefin to the iodide is 10 to 30:

1.

8. The method according to claim 1, characterized in that The reaction medium is selected from one or more of benzene, chlorobenzene, fluorobenzene, toluene, trifluorotoluene, xylene, mesitylene, anisole, 1,4-dioxane, tetrahydrofuran, acetonitrile, benzonitrile, acetone, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, ethylene glycol dimethyl ether, methyl tert-butyl ether, methyl cyclopentyl ether, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide.

9. The method according to claim 8, characterized in that The concentration of the olefin in the medium is 0.1 mol / mL to 0.5 mol / mL.

10. The method according to claim 1, characterized in that Also includes: The reaction product is subjected to column chromatography, wherein the mobile phase of the column chromatography is n-hexane and ethyl acetate in a volume ratio of 1 to 100:1.

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