CN-121974820-A - Efficient transfer hydrogenation method for non-activated olefin

CN121974820ACN 121974820 ACN121974820 ACN 121974820ACN-121974820-A

Abstract

The invention discloses a high-efficiency transfer hydrogenation method of non-activated olefin, which comprises the following steps of adding a non-activated alkenyl amide compound, nickel acetylacetonate dihydrate, phenylsilane, water and cesium pivalate into an organic solvent 1, 4-dioxane, reacting at room temperature under the condition of nitrogen for 12 hours, and carrying out post-treatment (extraction and column chromatography separation) after the reaction is completed to obtain a corresponding alkyl chloride compound. In the invention, phenylsilane and water are directly utilized as hydrogen sources, so that the direct and practical use of hydrogen can be avoided, the operation is simple and convenient, and the efficient construction of C (sp 3 )-C(sp 3 ) bonds can be realized through transfer hydrogenation of non-activated olefin. The conversion reaction condition is extremely mild, the reaction activity is high, and the method has the advantages of excellent atom economy, excellent step economy, wide substrate application range, good functional group compatibility and the like. It is worth noting that the synthesis method is also suitable for the post-modification of drug molecules, and is expected to further increase the drug properties of the molecules.

Inventors

LV NINGNING
YE WEICHENG
Chai Suhang
WANG CANHAO
LIU HANG
SiTu Duting
FENG JINGQI
LI ZHEFENG
Zhou si
KANG QI

Assignees

温州大学

Dates

Publication Date: 20260505
Application Date: 20251214

Claims (8)

1. The mild and efficient transfer hydrogenation method of the non-activated olefin is characterized by comprising the following steps of adding a non-activated alkenyl amide compound, a nickel salt catalyst, silane, water and an additive into an organic solvent, controlling the temperature to be 20-40 ℃ under the condition of nitrogen atmosphere, reacting for 10-14 h, and after the reaction is completed, carrying out post treatment to obtain a transfer hydrogenation product constructed by a corresponding C (sp 3 )-C(sp 3 ) bond; the structure of the non-activated alkenyl amide compound is shown as a formula (II): The structure of the transfer hydrogenation product is shown as a formula (I): In the formulas (I) - (II), R 1 is selected from one of substituted or unsubstituted phenyl, naphthyl, pyridyl, picolyl, quinolyl, C 1 ～C 6 alkyl and C 5 ～C 8 cycloalkyl, and the substituent on the phenyl is selected from one or more of halogen, trifluoromethyl, C 1 ～C 4 alkoxycarbonyl, C 1 ～C 4 alkanoyl, C 1 ～C 4 alkoxy, benzyl or C 1 ～C 4 alkyl; R 2 is selected from one or more of H, C 1 ～C 4 alkyl, phenyl, C 5 ～C 8 cyclopentyl; n is equal to 1, 2 or 3.
2. The transfer hydrogenation process according to claim 1, wherein R 1 is selected from one of substituted or unsubstituted phenyl, naphthyl, picolyl, quinolinyl, cyclopentyl, C 1 ～C 6 alkyl, the substituents on the phenyl are selected from one or more of fluoro, bromo, trifluoromethyl, methoxycarbonyl, acetyl, methoxy and ethyl, R 2 is selected from one or more of H, methyl, ethyl, phenyl and cyclopentyl, and n is equal to 1, 2 or 3.
3. The transfer hydrogenation process according to claim 1, wherein said organic solvent is 1, 4-dioxane.
4. The method of claim 1, wherein the nickel salt catalyst is nickel acetylacetonate dihydrate.
5. The transfer hydrogenation process according to claim 1 wherein said silane is phenylsilane (PhSiH 3 ) and said silane and water together comprise a hydrogen source.
6. The transfer hydrogenation process according to claim 1, wherein said additive is cesium pivalate.
7. The transfer hydrogenation method according to claim 1, wherein the molar ratio of the alkenylamide compound, the silane and the water is 1:2.5-3.5:3.5-4.5.
8. The transfer hydrogenation process according to claim 1, wherein said transfer hydrogenation product is one of the following compounds:

Description

Efficient transfer hydrogenation method for non-activated olefin Technical Field The invention belongs to the field of organic synthesis, and in particular relates to a simple and efficient synthesis method for nickel-catalyzed non-activated olefin transfer hydrogenation reaction. Background The C (sp 3)-C(sp3) bond is the core structural backbone of organic compounds, commonly found in drug molecules, natural products and functional organic molecules. It is worth emphasizing that increasing the proportion of sp 3 -hybridized carbon atoms may further enhance the drug-forming properties of the organic molecule. Therefore, the research of the bond reaction of C (sp 3)-C(sp3) has been a research hotspot in the field of organic synthesis. Among the reactions constructed with numerous C (sp 3)-C(sp3), the hydrogenation reduction of bulk chemical olefins is one of the most direct and efficient synthetic methods. Classical olefin hydrogenation reduction conversion mainly depends on catalytic hydrogenation reaction of transition metal, storage and transportation of hydrogen have great potential safety hazards, and a reaction system depends on a high-pressure device, so that the reaction has great safety problems in the actual production process. In recent years, transfer hydrogenation of olefins has been attracting attention from chemists by using hydrogen donors such as boranes, silanes, formic acid, alcohols, etc. instead of hydrogen, and by virtue of their operational safety and sustainable development. However, the use of expensive ligands in the transfer hydrogenation of most olefins to achieve catalytic recycling of the reaction is currently required, resulting in a significant reduction in the economy of the reaction. Therefore, in order to meet the green chemical development concept, the development of the low-cost transition metal catalytic olefin transfer hydrogenation reaction without ligand participation has important research value and practical significance. Disclosure of Invention The invention provides a mild, simple and convenient synthesis method for non-activated olefin transfer hydrogenation reaction, which can avoid direct use of hydrogen and realize efficient construction of a C (sp 3)-C(sp3) bond in one step. The synthesis method directly uses green and economic nickel acetylacetonate dihydrate as a catalyst, silane and water as hydrogen sources, cesium pivalate as an additive, has the advantages of broad-spectrum substrate application range, excellent functional group compatibility, excellent reactivity and the like, and shows excellent step economy and atom economy. The simple and efficient synthesis process of non-activated olefin transfer hydrogenation includes the steps of adding non-activated alkenyl amide compound, nickel acetylacetonate dihydrate, phenylsilane, water and cesium pivalate additive into organic solvent, reaction at 20-40 deg.c for 10-14 hr under nitrogen condition, and post treatment to obtain corresponding transfer hydrogenation product; the structure of the non-activated alkenyl amide compound is shown as a formula (II): The structure of the transfer hydrogenation product is shown as a formula (I): In the formulas (I) - (II), R 1 is selected from one or more of substituted or unsubstituted phenyl, naphthyl, pyridyl, picolyl, quinolyl, C 1～C6 alkyl and C 5～C8 cycloalkyl, and the substituent on the phenyl is selected from halogen, trifluoromethyl, C 1～C4 alkoxycarbonyl, C 1～C4 alkanoyl, C 1～C4 alkoxy, benzyl or C 1～C4 alkyl; R 2 is selected from one or more of H, C 1～C4 alkyl, C 5～C8 cyclopentyl; n is equal to 1, 2 or 3. In the invention, directly utilizing the non-activated alkenyl amide which is simple and easy to prepare and wide in source as a substrate, directly utilizing phenylsilane and water as hydrogen sources in a nickel catalytic system, and efficiently realizing transfer hydrogenation reaction of non-activated olefin at room temperature under the condition of no ligand. Preferably, R 1 is selected from one or more of substituted or unsubstituted phenyl, naphthyl, picolyl, quinolinyl, cyclopentyl, C 1～C6 alkyl, the substituents on the phenyl groups being selected from fluoro, bromo, trifluoromethyl, methoxycarbonyl, acetyl, methoxy and ethyl; preferably R 2 is selected from one or more of H, methyl, ethyl, phenyl and cyclopentyl, n is equal to 1, 2 or 3. Preferably, the nickel catalyst is nickel acetylacetonate dihydrate. Preferably, the hydrogen source is phenylsilane and water. Preferably, the molar ratio of the alkenyl amide compound, the silane and the water is 1:2.5-3.5:3.5-4.5. Preferably, the organic solvent is 1, 4-dioxane. Preferably, the reaction gas atmosphere is under nitrogen. Preferably, the reaction temperature is room temperature and the reaction time is 10 to 14 hours. Compared with the prior art, the invention has the beneficial effects that: (1) The nickel salt with low cost and low toxicity is directly used as a catalyst to realize the tran