Synthetic Access to Fluorocyclopropylidenes

Herein we report an approach for the straightforward preparation of fluorocyclopropylidene group from aldehydes and ketones via Julia- Kocienski olefination using the newly developed reagent 5-((2-fluorocyclo-propyl)sulfonyl)-1-phenyl-1H-tetrazole. Derivatization of monofluorocyclopro-pylidene compounds includes hydrogenation to deliver fluorocyclopropylmethyl compounds and fluorinated cyclobutanones. The utility of the described method is demonstrated by the synthesis of a fluorocyclopropyl-containing analogue of ibuprofen. Bioisosteric replacement of isobutyl with the fluorocyclopropyl group may be used for tuning biological properties of drug molecules.

Automated summary

Here we describe a direct method for the preparation of the fluorocyclopropylidene group from aldehydes and ketones via Julia-Kocienski olefination using a newly developed reagent. The utility of this method is demonstrated by the synthesis of a fluorocyclopropyl-containing analogue of ibuprofen, showing its potential in tuning the biological properties of drugs through bioisosteric replacement.