Selective defluorination of trifluoromethyl substituents by conformationally induced remote substitution

Angew Chem Int Ed Engl. 2024 Apr 8:e202403477. doi: 10.1002/anie.202403477. Online ahead of print.ABSTRACTThe selective reduction of an aromatic trifluoromethyl substituent to a difluoromethyl substituent may be achieved by base-promoted elimination to form a difluoro-p-quinomethide which is trapped by an intramolecular nucleophile. High yields are obtained when the nucleophilic trap entails the conformationally favoured cyclisation of an aminoisobutyric acid (Aib) derivative. The resulting cyclised difluoromethyl-substituted arylimidazolidinone products are readily converted to versatile difluoromethyl-substituted aldehydes by reduction and hydrolysis. Defluorination is successful on a range of benzenoid (both para and ortho CF3 substituted) and heterocyclic substrates. Double defluorination may likewise be achieved sequentially, or in a single step from an Aib dipeptide derivative.PMID:38587304 | DOI:10.1002/anie.202403477

Source: Angewandte Chemie - April 8, 2024 Category: Chemistry Authors: Mehul H Jesani Maria Schwarz Shiwhu Kim Finlay L Evans Alexander White Alex Browning Roman Abrams Jonathan Clayden Source Type: research