A General Approach to Various Five- and Six-Membered gem-Difluoroheterocycles Application to the Synthesis of Fluorinated Analogues of Sedamine

Layal Hariss (1) , Rima Ibrahim (2, 1) , Nada Jaber (1) , Thierry Roisnel (3) , René Grée (3) , Ali Hachem (1)

1 LU / ULB - الجامعة اللبنانية [بيروت] = Lebanese University [Beirut] = Université libanaise [Beyrouth]
2 Lebanese Univ, Fac Sci 2, EC2M
3 ISCR - Institut des Sciences Chimiques de Rennes

A new synthesis of a group of O-, S- and N-heterocycles with a gem-difluoro group in position to the heteroatom has been developed, starting from easily accessible gem-difluoro propargylic derivatives. This tandem process involves a base-induced isomerization followed by an intramolecular 1,4 hetero-Michael addition. This methodology is suitable for the preparation of five- and six-membered heterocycles and it has been successfully applied to the synthesis of the 3,3-difluoro analogues of (+/-)-sedamine III, (+/-)-allosedamine V, (+/-)-norallosedamine II, and (+/-)-norsedamine IV.

Mots clés: Fluorinated compounds; Fluorine; Propargylic fluorides; Heterocycles; Sedamine; Alkaloids

Domaines: Chimie

Layal Hariss, Rima Ibrahim, Nada Jaber, Thierry Roisnel, René Grée, et al.. A General Approach to Various Five- and Six-Membered gem-Difluoroheterocycles Application to the Synthesis of Fluorinated Analogues of Sedamine. European Journal of Organic Chemistry, 2018, 2018 (27-28), pp.3782-3791. ⟨10.1002/ejoc.201800371⟩. ⟨hal-01861423⟩