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

## TL;DR

A new chemical method allows precise modification of fluorinated compounds to create unique structures with controlled selectivity.

## Contribution

A novel one-pot dearomatizative strategy for fluorinated oxadiazoles with regioselective N-functionalization is introduced.

## Key findings

- The method enables selective formation of 2,5-dihydro or 4,5-dihydro isomers with excellent regiocontrol.
- Steric properties of nucleophiles are identified as key factors influencing regioselectivity.
- The process allows further derivatization of intermediates using electrophilic platforms.

## Abstract

The constitutive low aromaticity of easily accessible 5-trifluoromethyl-1,2,4-oxadiazoles is explored to enable editing modification to the corresponding unprecedented gem-disubstituted 1,2,4-oxadiazolines. The operation proceeds via 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.e. LiCH2Br).

The constitutive low aromaticity of easily accessible 5-trifluoromethyl-1,2,4-oxadiazoles is explored to enable editing modification to the corresponding unprecedented gem-disubstituted 1,2,4-oxadiazolines.