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gem-Difluoroolefination of Amides
Alexey L Trifonov1, Alexander D Dilman1
1N. D. Zelinsky Institute of Organic Chemistry, 119991, Moscow, Leninsky prosp. 47, Russian Federation.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|October 10, 2023
Summary
A new metal-free method efficiently converts amides into gem-difluoroolefins using in-situ generated reagents. This one-pot reaction offers a fast, low-temperature pathway to valuable fluoroalkylated amines.
Area of Science:
- Organic Chemistry
- Fluorine Chemistry
Background:
- Amides are versatile starting materials in organic synthesis.
- Efficient methods for introducing gem-difluoroolefin moieties are highly sought after.
Purpose of the Study:
- To develop a novel metal-free, one-pot protocol for the gem-difluoroolefination of amides.
- To explore the utility of the generated gem-difluoroenamines in subsequent synthetic transformations.
Main Methods:
- Generation of α-chloroiminium salts in situ from amides.
- Reaction of α-chloroiminium salts with a difluorinated phosphorus ylide, generated from difluorocarbene and triphenylphosphine.
- Nucleophile-assisted dephosphorylation mechanism.
Main Results:
- A one-pot, metal-free gem-difluoroolefination of amides was achieved.
- The reaction proceeds rapidly (within one hour) at low temperatures.
- The synthesized gem-difluoroenamines serve as precursors for various fluoroalkylated amines.
Conclusions:
- The described method provides a convenient and efficient route to gem-difluoroolefins from amides.
- This approach expands the toolkit for synthesizing fluorinated organic compounds.
- The generated fluoroalkylated amines have potential applications in medicinal chemistry and materials science.
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