<i>One-pot</i> dearomatizative telescoped addition of <i>C</i> -nucleophiles to fluorinated 1,2,4-oxadiazoles followed by regioselective <i>N</i> -functionalization

The constitutive low aromaticity of easily accessible 5-trifluoromethyl-1,2,4-oxadiazoles is explored to enable editing modification to the corresponding unprecedented <i>gem</i>-disubstituted 1,2,4-oxadiazolines. The operation proceeds <i>via</i> the nucleophilic addition of diverse carbon-centered nucleophiles with excellent regiocontrol (in almost all cases), thus selectively furnishing either the 2,5-dihydro or 4,5-dihydro isomers. The process, which also exhibits high chemocontrol, enables further derivatization of the intermediate anion with externally added electrophilic platforms. Calculations support the experimental evidence and identify intrinsic steric properties of the nucleophiles as a key factor controlling regioselectivity, thus rationalizing the non-optimal outcome observed in particular circumstances (<i>i.e.</i> LiCH₂Br).