One-pot Dearomatizative C-Nucleophiles Telescoped Addition to Fluorinated 1,2,4-Oxadiazoles - Regioselective N-Functionalization

Abstract

The constitutive low aromaticity of easily accessible 5-trifluoromethyl-1,2,4-oxadiazoles is explored for the editing modification to the corresponding unprecedented gem-disubstituted 1,2,4-oxadiazolines. The operation consiting in the nucleophilic addition of diverse carbon-centered nucleophiles occurs with excellent regiocontrol (in almost all cases), thus furnishing selectively 2,5-dihydro or 4,5-dihydro isomers. The process - documenting also high chemocontrol – enables the further derivatization of the intermediate anion with externally added electrophilic platforms. Calculations supporting the experimental evidences, attribute a key role in controlling the regioselectivity to intrinsic steric factors of the nucleophiles thus, rationalizing the non optimal outcome observed in particular circumstances (i.e. with LiCH 2 Br).