Introduction of Trifluoroethylamine as Amide Isostere by C–H Functionalization of Heteroarenes

Marie-Gabrielle Braun (1) , Georgette Castanedo (1) , Ling Qin (2) , Patrick Salvo (1) , Samir Z. Zard (2)

1 Department of Discovery Chemistry
2 DCSO - Laboratoire de synthèse organique

A direct and efficient introduction of a trifluoroethylamine motif into various heteroaromatic structures, using a readily available xanthate S-[1-(N-acetylamino)-2,2,2-trifluoroethyl]-O-ethyl dithiocarbonate (5), is reported. Medicinally relevant trifluoroethylaminated heteroarenes containing a wide range of functional groups were successfully synthesized under mild conditions. This amide isostere could be introduced into both electron-rich and -poor heteroarenes to give the desired products in one step. The beneficial effect of camphorsulfonic acid (CSA) was also demonstrated with electron-deficient heteroarenes.

Domaines: Chimie organique

Marie-Gabrielle Braun, Georgette Castanedo, Ling Qin, Patrick Salvo, Samir Z. Zard. Introduction of Trifluoroethylamine as Amide Isostere by C–H Functionalization of Heteroarenes. Organic Letters, 2017, 19 (15), pp.4090-4093. ⟨10.1021/acs.orglett.7b01880⟩. ⟨hal-02094015⟩