Organic Chemistry

Carbodefluorination via a carbene-initiated rearrangement strategy

Authors

Abstract

The C–F bond cleavage and C–C bond formation (i.e., carbodefluorination) of readily accessible (per)fluoroalkyl groups constitutes an atom-economical and efficient route to partially fluorinated compounds. However, the selective mono-carbodefluorination of trifluoromethyl (CF3) groups remains a formidable challenge, due to the notorious inertness of C–F bond and the risk of over-defluorination arising from C–F bond strength decrease as the defluorination proceeds. Herein, we report a carbene-initiated rearrangement strategy for the carbodefluorination of fluoroalkyl ketones with β,γ-unsaturated alcohols. The reaction starts with formation of a silver carbene from a fluoroalkyl ketone N-triftosylhydrazone, followed by nucleophilic addition of a β,γ-unsaturated alcohol to form a key oxonium ylide intermediate, which triggers selective C–F bond cleavage by HF elimination and C–C bond formation through Claisen rearrangement of in situ generated difluorovinyl ether. This method described here is versatile and enables the conversion of fluoroalkyl ketones into skeletally and functionally diverse α-mono- and α,α-difluoro-γ,δ-unsaturated ketones. The reaction mechanism and the origin of chemoselectivity were established by experimental and computational approaches. Collectively, current strategy integrates successive C–F bond cleavage and C–C bond formation on a single molecule entity by an intramolecular cascade process, thereby offering significant advances over existing stepwise strategies in term of selectivity, efficiency, functional group tolerance, etc.

Content

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Supplementary material

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Supporting Information
Detailed information about the experimental procedures as well as analytical data is provided in the Supplementary Information.