A nickel-catalyzed iron-mediated fluoroalkylation of alkynes to synthesize (z)-alkenes and products

A technology for fluoroalkyl and fluoroalkylation of alkynes, applied in the field of organic compound synthesis, can solve the problems of unstable E/Z selectivity, high price, no economical practicability, etc., and expand the scope of preparation of substrates , mild conditions, good applicability

Active Publication Date: 2022-05-03
NANJING TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] The hydrofluoroalkylation reaction of alkynes has the disadvantages that the catalysts (Pt, Ir) used are relatively expensive, do not have wide economic practicability, E / Z selectivity is unstable, or require special substrates, etc.
Iron(0) is one of the most abundant and cheapest metals on earth compared with other metals (such as lithium, magnesium, aluminum, zinc, manganese, tin), but its use in organic synthesis has not been widely recognized. to develop

Method used

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  • A nickel-catalyzed iron-mediated fluoroalkylation of alkynes to synthesize (z)-alkenes and products
  • A nickel-catalyzed iron-mediated fluoroalkylation of alkynes to synthesize (z)-alkenes and products
  • A nickel-catalyzed iron-mediated fluoroalkylation of alkynes to synthesize (z)-alkenes and products

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] (1) Iron powder (168.0 mg, 3.0 mmol, 3.0 equiv.) and DMF (2 mL) were sequentially added to a 10 mL Schlenk flask. 1,2-Dibromoethane (28mg, 0.15mmol) was added, the reaction flask was heated to 320°C, maintained for 35 seconds and then cooled to room temperature. Then trimethylchlorosilane (22mg, 0.15mmol) was added, heated with an electric heat gun at 320°C for 35 seconds, and then cooled to room temperature to complete the activation of the iron powder.

[0042] (2) After cooling to room temperature, add NiCl to the reaction flask in turn 2(13mg, 0.1mmol, 0.1equiv.), LiI (267.7mg, 2.0mmol, 2.0equiv.), DPEPhos (108mg, 0.2mmol, 0.2equiv.), 2-bromo-2,2-difluoro-3-acetic acid Ethyl ester (3.0 mmol, 3.0 equiv.) and 4-chlorophenylacetylene (1.0 mmol, 1.0 equiv.). The reaction mixture was stirred at 60 °C for 24 h, then washed with saturated NH 4 The Cl solution was quenched and extracted with ethyl acetate (20 mL×3). The combined organic phases were successively washed w...

Embodiment 2

[0047] (1) Iron powder (168.0 mg, 3.0 mmol, 3.0 equiv.) and DMF (2 mL) were sequentially added to a 10 mL Schlenk flask. 1,2-Dibromoethane (28mg, 0.15mmol) was added, the reaction flask was heated to 320°C, maintained for 35 seconds and then cooled to room temperature. Then trimethylchlorosilane (22mg, 0.15mmol) was added, heated with an electric heat gun at 320°C for 35 seconds, and then cooled to room temperature to complete the activation of the iron powder.

[0048] (2) After cooling to room temperature, add NiCl to the reaction flask in turn 2 (13mg, 0.1mmol, 0.1equiv.), LiI (267.7mg, 2.0mmol, 2.0equiv.), DPEPhos (108mg, 0.2mmol, 0.2equiv.), perfluoroiodoethane (3.0mmol, 3.0equiv.) and 4-cyanophenylacetylene (1.0 mmol, 1.0 equiv.). The reaction mixture was stirred at 100 °C for 24 h, then washed with saturated NH 4 The Cl solution was quenched and extracted with ethyl acetate (20 mL×3). The combined organic phases were successively washed with saturated brine (20 mL),...

Embodiment 3

[0053] (1) Iron powder (168.0 mg, 3.0 mmol, 3.0 equiv.) and DMF (2 mL) were sequentially added to a 10 mL Schlenk flask. 1,2-Dibromoethane (28mg, 0.15mmol) was added, the reaction flask was heated to 320°C, maintained for 35 seconds and then cooled to room temperature. Then trimethylchlorosilane (22mg, 0.15mmol) was added, heated with an electric heat gun at 320°C for 35 seconds, and then cooled to room temperature to complete the activation of the iron powder.

[0054] (2) After cooling to room temperature, add NiCl to the reaction flask in turn 2 (13mg, 0.1mmol, 0.1equiv.), LiI (267.7mg, 2.0mmol, 2.0equiv.), DPEPhos (108mg, 0.2mmol, 0.2equiv.), 2-bromo-2,2-difluoro-3-acetic acid Ethyl ester (3.0 mmol, 3.0 equiv.) and 2-ethynylbenzyl 2-(4-isobutylphenyl)propionate (1.0 mmol, 1.0 equiv.). The reaction mixture was stirred at 60 °C for 24 h, then washed with saturated NH 4 The Cl solution was quenched and extracted with ethyl acetate (20 mL×3). The combined organic phases we...

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Abstract

The invention discloses a nickel-catalyzed iron-mediated fluoroalkylation of alkynes to synthesize (Z)-alkenes and its products. The method includes sequentially adding a metal accelerator and an ultra-dry solvent, using 1,2-dibromoethyl alkane and trimethylchlorosilane sequentially activate the metal; after cooling, the alkyne, fluoroalkylated halide, catalyst, ligand, and additives are sequentially added, and the reaction mixture is stirred vigorously under a nitrogen atmosphere; saturated ammonium chloride solution is used for After quenching, the reaction product was washed, extracted and dried, and separated by column chromatography to obtain the target product. The present invention uses cheap and easy-to-obtain iron powder as a reaction accelerator to synthesize (Z)-fluoroalkylated olefins, which expands the scope of preparation substrates for such compounds; the preparation method of the present invention has mild conditions and can be combined with various functional groups Compatible, and also shows good applicability in the modification of functional groups of some complex molecules.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis, and specifically relates to a method and a product for synthesizing (Z)-alkenes by nickel-catalyzed iron-mediated alkyne fluoroalkylation. Background technique [0002] In recent decades, it has been generally recognized that the introduction of fluorine atoms or fluorine-containing functional groups into organic molecules will significantly enhance the lipophilicity, metabolic stability and bioavailability of the parent molecule, which makes it widely used in medicine, agrochemical potential applications in food and materials science. Since olefins are commonly used raw materials in chemical synthesis, it is particularly important to develop synthetic methods for fluoroalkylated olefins. [0003] The hydrofluoroalkylation reaction of alkynes has the disadvantages of using relatively expensive catalysts (Pt, Ir), not having wide economic practicability, unstable E / Z selectivit...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C69/65C07C67/347C07C255/50C07C253/30C07C255/57C07D295/185C07J1/00C07D493/14C07D313/12
CPCC07C69/65C07C67/347C07C255/50C07C253/30C07C255/57C07D295/185C07J1/0059C07D493/14C07D313/12C07B2200/09
Inventor 沈志良褚雪强王雅文李祥瑞
Owner NANJING TECH UNIV
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