Selective Defluorination of Trifluoromethyl Substituents by Conformationally Induced Remote Substitution

The selective reduction of an aromatictrifluoromethyl substituent to a difluoromethyl substitu-ent may be achieved by base-promoted elimination toform a difluoro-p-quinomethide which is trapped by anintramolecular nucleophile. High yields are obtainedwhen the nucleophilic trap entails the conformationallyfavoured cyclisation of an aminoisobutyric acid (Aib)derivative. The resulting cyclised difluoromethyl-substi-tuted arylimidazolidinone products are readily con-verted to versatile difluoromethyl-substituted aldehydesby reduction and hydrolysis. Defluorination is successfulon a range of benzenoid (both para and ortho CF3-substituted) and heterocyclic substrates. Double de-fluorination may likewise be achieved sequentially, or ina single step, from an Aib dipeptide derivative.