Recent synthetic methods towards the –OCHF2 moiety

Anaïs Loison (1) , Fabien Toulgoat (2, 3) , Thierry Billard (3, 4) , Gilles Hanquet (1) , Armen Panossian (1) , Frédéric Leroux (1)

1 LIMA - Laboratoire d'innovation moléculaire et applications
2 CPE - École Supérieure de Chimie Physique Électronique de Lyon
3 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
4 CERMEP - imagerie du vivant - Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant

The fluorine atom and fluorinated substituents are currently key motifs in pharmaceutical and agrochemical active ingredients, since they often beneficially modulate the physico-chemical and biological properties of the latter when installed in place of a hydrogen substituent. Among such fluorinated moieties, –OCHF2 is emerging as an interesting group, which is notably capable of forming a hydrogen bond. These appealing properties have led to a growing need for introduction methods of this group. In this review we summarize all current methods allowing access to the –OCHF2 moiety. We will hence discuss procedures applicable to either aromatic or aliphatic substrates, and based on different disconnections, including difluoromethylation of alcohols, or radical addition onto arenes

Mots clés: Fluorine; Difluoromethyl ether; Difluoromethyl ester; Difluoromethoxylation; O-Difluoromethylation

Domaines: Chimie organique

Anaïs Loison, Fabien Toulgoat, Thierry Billard, Gilles Hanquet, Armen Panossian, et al.. Recent synthetic methods towards the –OCHF2 moiety. Tetrahedron, 2021, 99, pp.132458. ⟨10.1016/j.tet.2021.132458⟩. ⟨hal-03517915⟩