There is a large and ever-growing demand for new methods to incorporate fluorine atoms into molecules, especially those with biological relevance. Fluorofunctionalization methods for carboxylic acids, despite these moieties being among the most common functionalities in the body, have seen little advancement in recent years. We have developed a procedure for the O-difluoromethylation of carboxylic acids using TMSCF2Br as the difluorocarbene source, providing access to the corresponding difluoromethyl esters. We have found that the reaction runs smoothly at room temperature in an acetonitrile/water solvent system under air to give moderate to excellent yields of the –OCF2H products. Bromofluorocarbene is a much less explored synthetic intermediate than difluorocarbene, largely due to a lack of convenient ways to generate it. Incorporation of this fragment into organic molecules introduces the valuable fluorine atom, and the C–Br bond can then serve as an active handle for further functionalization. With that motivation, we have developed a new method for [2+1] cycloaddition of bromofluorocarbene with alkenes to give gem-bromofluorocyclopropanes. The reactions proceed smoothly under mild conditions, employing an accessible and inexpensive source of bromofluorocarbene. The reaction scope and potential modification of products will be discussed.

O-difluoromethylation of carboxylic acids with CF2 carbene and [2+1] cycloadditions with CFBr carbene: New methods of dihalocarbene incorporation into organic molecules

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.