Fluorinated Olefins as Traceless Linchpins for Modular Non-Directed C–H Alkenylation Reactions
- 1Institute of Chemistry, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, Halle (Saale), Germany, 06120
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.
Related
- Mechanistic Insights into the Non-Equilibrium Synthesis of Highly Fluorinated Cation-Disordered Rock-Salt Cathodes: Solid-State Thermal vs. Mechanochemical Reactions
- Regioselective oxidative alkenylation of 4-azaindazole and 7-azaindazole N-oxides at the six-membered ring: N-oxide-mediated hydroxylation
- Copper‐Catalyzed Regioconvergent and Stereodivergent Allylation and Alkenylation of Styrenes via Bromo‐Acyloxy Transposition
- Traceless trimethyl-lock translators for thiol-mediated uptake of native proteins as covalent constructs
- Reppe-Type Regioselective Assembly of Meta-Teraryls using Phenyl Vinyl Sulfone as a Traceless Acetylene Surrogate
BibTeX
@misc{kotwal2026fluorinated,
title = {{Fluorinated Olefins as Traceless Linchpins for Modular Non-Directed C–H Alkenylation Reactions}},
author = {Namrata Kotwal and Deepak Sharma and Anirban Mandal and Claire Empel},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008958/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008958/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Fluorinated Olefins as Traceless Linchpins for Modular Non-Directed C–H Alkenylation Reactions
AU - Namrata Kotwal
AU - Deepak Sharma
AU - Anirban Mandal
AU - Claire Empel
PY - 2026
DA - 2026/09/16
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008958/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008958/v1
AB - 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.
ER -