Defluorinative Multicomponent Cascade Reaction of Trifluoromethylarenes via Photoexcited Palladium Catalysis
Zhibin Li, Lei Bao, Kaihang Wei, Bei‐Bei Zhan, Ping Lu, Xiaheng Zhang
Abstract
The incorporation of aromatic difluoromethyl motifs has proven to be a fruitful strategy for enhancing the therapeutic profiles of modern pharmaceutical candidates. While the defluorofunctionalization of trifluoromethylarenes offers a promising pathway toward diverse aromatic difluoromethyl compounds, current methods are predominantly limited to two-component reactions. Multicomponent cascade reactions (MCRs) involving a transient aromatic difluoromethyl radical are still uncommon and highly sought after, owing to their capacity to rapidly generate challenging molecular structures. In this study, we present a photocatalytic manifold that combines commercially available trifluoromethylarenes, feedstock dienes, and various nucleophiles to achieve a modular defluorinative MCR. This method features mild reaction conditions and a broad substrate scope with excellent functional group compatibility. Furthermore, this protocol enables a previously unreported process of defluorinative editing for the resulting MCR aromatic difluoromethyl adducts. Preliminary mechanistic studies support the proposed photoexcited palladium catalytic cycle.