Defluorinative Multicomponent Cascade Reaction of\nTrifluoromethylarenes via Photoexcited Palladium Catalysis

The incorporation\nof aromatic difluoromethyl motifs has proven\nto be a fruitful strategy for enhancing the therapeutic profiles of\nmodern pharmaceutical candidates. While the defluorofunctionalization\nof trifluoromethylarenes offers a promising pathway toward diverse\naromatic difluoromethyl compounds, current methods are predominantly\nlimited to two-component reactions. Multicomponent cascade reactions\n(MCRs) involving a transient aromatic difluoromethyl radical are still\nuncommon and highly sought after, owing to their capacity to rapidly\ngenerate challenging molecular structures. In this study, we present\na photocatalytic manifold that combines commercially available trifluoromethylarenes,\nfeedstock dienes, and various nucleophiles to achieve a modular defluorinative\nMCR. This method features mild reaction conditions and a broad substrate\nscope with excellent functional group compatibility. Furthermore,\nthis protocol enables a previously unreported process of defluorinative\nediting for the resulting MCR aromatic difluoromethyl adducts. Preliminary\nmechanistic studies support the proposed photoexcited palladium catalytic\ncycle.