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

Anaïs Loison (1) , Gilles Hanquet (1) , Fabien Toulgoat (2, 3) , Thierry Billard (2) , Armen Panossian (1) , Frédéric R Leroux (1)

1 LIMA - Laboratoire d'innovation moléculaire et applications
2 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
3 CPE - École Supérieure de Chimie Physique Électronique de Lyon

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

Mots clés: Fluorine; Heterocycles; Ketones; Difluoromethoxy; Building blocks

Domaines: Chimie organique

Anaïs Loison, Gilles Hanquet, Fabien Toulgoat, Thierry Billard, Armen Panossian, et al.. Difluoromethoxylated Ketones as Building Blocks for the Synthesis of Challenging OCF2H‐Bearing N‐Heterocycles.. European Journal of Organic Chemistry, inPress, ⟨10.1002/ejoc.202300695⟩. ⟨hal-04163739v2⟩