Deoxyfluorination of α-N-phthaloyl cycloalkanones with bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor)

•Deoxo-Fluor has been investigated for the deoxyfluorination of α-N-protected cycloalkanones.•The deoxyfluorination of an α-N-phthaloyl cyclobutanone gave the gem- and vic-difluorides.•The deoxyfluorination of an α-N-benzoyl cyclobutanone gave an oxazole derivative.•These reactions involved the formation of a cationic species as intermediates through neighboring group participation.•The presence or absence of a hydrogen atom on the protected amine was critical to determining the outcome of the reaction.

The deoxyfluorination of α-N-phthaloyl cyclobutanone with bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) produced a gem-difluoride product together with a vic-difluoride bearing a cyclopropane ring. In contrast, the deoxyfluorination of the corresponding α-N-phthaloyl cyclopentanone produced the gem-difluoride only. Furthermore, the deoxyfluorination of the corresponding α-N-phthaloyl cyclohexanone produced an intramolecular cyclization product with two fluorine atoms as the main product, which provided the starting material after workup. Cationic species formed through neighboring group participation are most likely the key intermediates in these reactions. Control experiments using N-benzoyl congeners produced oxazole or oxazoline derivatives, indicating that the presence or absence of a hydrogen atom on the protected amine moiety was critical to determining the reaction path.

Graphical abstractThe deoxyfluorination of α-N-phthaloyl cyclobutanone with Deoxo-Fluor produced a gem-difluoride product together with a vic-difluoride bearing a cyclopropane ring. The deoxyfluorination of the corresponding α-N-phthaloyl cyclohexanone produced an intramolecular cyclization product with two fluorine atoms, which provided the starting material after workup.Figure optionsDownload full-size imageDownload as PowerPoint slide