Synthetic Access to Fluorocyclopropylidenes

• DOI: 10.1021/acs.orglett.3c00579
• Publication Date: 2023-03-30T16:11:39Z
• Authors: Renate Melngaile; Melita Videja; Janis Kuka; Artis Kinens; Dzintars Zacs; Janis Veliks

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-fluorocyclopropyl)sulfonyl)-1-phenyl-1H-tetrazole. Derivatization of monofluorocyclopropylidene 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.