Difluoromethoxylated Ketones as Building Blocks for the Synthesis of Challenging OCF2H‐Bearing N‐Heterocycles

We report herein an unprecedented synthesis of difluoromethoxylated nitrogen‐containing heterocycles from the corresponding α‐(difluoromethoxy)ketones as versatile building blocks. Pyrazoles, isoxazoles and pyrimidines could be obtained via an enaminone intermediate, whereas in the direct reaction o...

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Bibliographic Details
Published in:European journal of organic chemistry 2023-11, Vol.26 (42)
Main Authors: Loison, Anaïs, Hanquet, Gilles, Toulgoat, Fabien, Billard, Thierry, Panossian, Armen, Leroux, Frédéric R
Format: Article
Language:English
Subjects:
Chemical Sciences
Fluorination
Ketones
Organic chemistry
Pyrimidines
Synthesis
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Summary:We report herein an unprecedented synthesis of difluoromethoxylated nitrogen‐containing heterocycles from the corresponding α‐(difluoromethoxy)ketones as versatile building blocks. Pyrazoles, isoxazoles and pyrimidines could be obtained via an enaminone intermediate, whereas in the direct reaction of α‐(difluoromethoxy)ketones with arylhydrazines, a Fischer indole synthesis was achieved. All these scaffolds, which are uncommon, or even sometimes novel, due to the directly attached emerging fluorinated group (EFG) −OCF2H, might be of high potential in life sciences and appear as an interesting alternative to more and more controversial classical fluorinated groups, such as the ubiquitous trifluoromethyl group.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.202300695