Fluorinated Olefins as Traceless Linchpins for Modular Non-Directed C–H Alkenylation Reactions
Year: 2026
Type: preprint
Abstract: Palladium-catalyzed non-directed C–H olefination provides an attractive strategy for the direct functionalization of simple arenes, yet its modularity is typically limited by the need for prefunctionalized olefin coupling partners. Here, we report an unconventional tracelesslinchpin strategy using bromo-difluoromethyl-substituted olefins for the modular synthesis of cinnamic acid esters. In contrast to the expected formation of fluorinated alkenes, the fluorinated olefin undergoes palladium-catalyzed non-directed C–H functionalization followed by defluorinative transformation in the presence of alcohols, furnishing the corresponding cinnamic acid esters. The method tolerates a broad range of fluorinated and non-fluorinated alcohols as well as structurally diverse arenes, providing access to products in generally good to excellent yields and useful regioselectivities. The modular nature of the transformation further enables the late-stage functionalization of pharmaceutically relevant molecules and the direct synthesis of drug–drug and drug–natural product conjugates. Mechanistic studies support an initial C–H functionalization with the fluorinated olefin, followed by subsequent conversion of the resulting intermediate into the corresponding cinnamic acid esters.
Source: ChemRxiv
Institution: Martin Luther University Halle-Wittenberg
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7213451790