Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Process for synthesizing optical activity 2-(1'(Z) alkenyl iodo-alkyl) tetrahydrofuran

An alkenyl iodoalkyl, optically active technology, which is applied in the field of efficient synthesis of optically active 2-alkyl-substituted tetrahydrofuran compounds, can solve the problems of unfriendly and expensive environments, and achieve mild conditions and short reaction times Effect

Inactive Publication Date: 2009-05-27
ZHEJIANG UNIV
View PDF0 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods are often carried out by introducing expensive and environmentally unfriendly heavy metal catalysts and expensive chiral ligands

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Process for synthesizing optical activity 2-(1'(Z) alkenyl iodo-alkyl) tetrahydrofuran
  • Process for synthesizing optical activity 2-(1'(Z) alkenyl iodo-alkyl) tetrahydrofuran

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add (R)-4,5-diendecyl alcohol (33.4mg, 0.20mmol, 95% ee), dichloromethane, NIS (54.4mg, 0.24mmol) into the reaction tube, start stirring at room temperature, and react for 55min . Add saturated Na 2 S 2 o 3 solution, stirred until colorless, extracted with ether, dried over anhydrous sodium sulfate, filtered, concentrated, flash column chromatography to obtain (S)-2-(1-iodo-1(Z)-heptenyl)tetrahydrofuran and (R )-2-(1-iodo-1(E)-heptenyl)tetrahydrofuran liquid, 54.3 mg in total, 93% yield, Z / E=90 / 10.

[0023] 1 H NMR (300MHz, CDCl 3 )δ[6.31, (t, J=7.8Hz, E-isomer, 0.1H), 5.90(t, J=6.8Hz, Z-isomer, 0.9H)], 4.18(t, J=6.5Hz, 1H) , 4.08-3.95(m, 1H), 3.92-3.80(m, 1H), 2.21-2.10(m, 2H), 2.10-1.80(m, 4H), 1.46-1.22(m, 6H), 0.88(t, J=6.8Hz, 3H).

[0024] Under the protection of nitrogen, the mixture obtained above [(S)-2-(1-iodo-1(Z)-heptenyl)tetrahydrofuran and (R)-2-(1-iodo-1(E)-heptene base) tetrahydrofuran] (54.3mg, 0.18mmol, Z / E=90 / 10), propynyl alcohol (3.2mg, 0.05...

Embodiment 2

[0031] (R)-4,5-dienyl dodecanol (34.9mg, 0.19mmol, 98%ee), dichloromethane, NIS (54.7mg, 0.24mmol) were reacted at room temperature for 45min to obtain the product (S)-2 -(1-iodo-1(Z)-octenyl)tetrahydrofuran and (R)-2-(1-iodo-1(E)-octenyl)tetrahydrofuran total 51.7 mg, liquid, yield 88%, Z / E=90 / 10.

[0032] 1 H NMR (300MHz, CDCl 3 )δ[6.31(t, J=7.7Hz, E-isomer, 0.1H), 5.91(t, J=6.8Hz, Z-isomer, 0.9H)], 4.19(t, J=6.2Hz, 1H), 4.06-3.95(m, 1H), 3.92-3.80(m, 1H), 2.21-2.10(m, 2H), 2.10-1.80(m, 4H), 1.46-1.22(m, 8H), 0.87(m, 3H ).

[0033]Under the protection of nitrogen, the product [(S)-2-(1-iodo-1(Z)-octenyl)tetrahydrofuran obtained above was mixed with (R)-2-(1-iodo-1(E)-octene base) tetrahydrofuran] (51.7mg, 0.17mmol, Z / E=90 / 10), propynyl alcohol (2.7mg, 0.048mmol), diethylamine (3.2mg, 0.04mmol), bis(triphenylphosphine) Palladium dichloride (4.3mg, 0.006mmol) reacted with cuprous iodide (1.5mg, 0.008mmol) in anhydrous acetonitrile, added diethyl ether to quench the reac...

Embodiment 3

[0040] 1) Add N-iodosuccinimide (0.24mmol) di Chloromethane (1 mL), stirred at room temperature for 45-55 minutes;

[0041] 2) After step (1) was completed, water (10 mL) and saturated sodium thiosulfate (10 mL) were added, extracted with diethyl ether (20 mL×3), and dried over anhydrous sodium sulfate. Concentrate under reduced pressure after filtering off anhydrous sodium sulfate, and obtain the product after silica gel column chromatography;

[0042] 3) Transfer the product obtained in (2) to the reaction flask, then add bis(triphenylphosphine) palladium dichloride (0.007mmol), cuprous iodide (0.007mmol), propynyl alcohol (0.057mmol) ), diethylamine (0.06mmol) and anhydrous acetonitrile (2mL), stirred and reacted at room temperature for 20 minutes;

[0043] 4) After step (3) is completed, direct flash silica gel column chromatography to obtain (S)-2-(1'(Z)alkenyl iodoalkyl)tetrahydrofuran.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a method for synthesizing optically active (S)-2-(1'(Z)alkenyl iodoalkyl)tetrahydrofuran. An optically active (R)-4, 5-allenol is taken as a reaction substrate and is subjected to iodocyclization reaction with an electrophilic reagent, namely N-iodosuccinimide to generate the optically active (S)-2-(1'(Z)alkenyl iodoalkyl)tetrahydrofuran (large amount) and (R)-2-(1'(E)alkenyl iodoalkyl)tetrahydrofuran (small amount); and the optically active (S)-2-(1'(Z) alkenyl iodoalkyl)tetrahydrofuran with Z configuration is obtained by utilizing the speed difference that a Z / E isomer is subjected to Sonogashira coupling reaction with propiolic alcohol under the co-catalysis of dichlorobis(triphenylphosphine)palladium and cuprous iodide. The method has simple operation, is easy to obtain the raw material and the reagent, has the reaction with high region and stereoselectivity, can synchronously introduce a plurality of substitional groups, is easy to separate and purify a product, and is suitable to synthesize various substituted optically active tetrahydrofuran compounds.

Description

technical field [0001] The invention relates to a method for efficiently synthesizing optically active (S)-2-alkyl substituted tetrahydrofuran compounds. Background technique [0002] Tetrahydrofuran compounds are one of the very important intermediates in organic synthesis and one of the common structural units in natural products. At present, many compounds containing this skeleton have been proved to have many potential physiological activities, and have great development and utilization value in the field of biotechnology, medicine and pesticides. Optically active tetrahydrofuran compounds occupy a very important proportion in this type of compound. The (S)-2-alkyl-substituted tetrahydrofuran compounds reported in the past are mainly obtained by allenol or alkyne in the presence of chiral ligands. Ether self-closing reaction (Angew.Chem.Int.Ed.2007, 46, 283; J.Org.Chem.2004, 69, 8387.) or direct use of chiral allenol self-closing reaction (J.Am. Chem.Soc.2006, 128, 906...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D307/10C07B53/00
Inventor 麻生明吕博傅春玲
Owner ZHEJIANG UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com