Axial Chirality Control Through Palladium‐Catalyzed Alkenylation Reactions for the Atroposelective Synthesis of 4‐Arylquinolin‐2‐ones

Axially chiral biaryl scaffolds are privileged structures used in organic synthesis as ligands or chiral catalysts, but also present in natural and synthetic compounds with relevant biological properties. However, the enantioselective synthesis of atropoisomers through C─H activation reactions remains challenging, with few approaches described that rely on de novo construction of a (hetero)arene with the chirality being installed by simultaneous ring formation. We herein disclose a Pd(II)‐catalyzed intramolecular C─H alkenylation of cinnamides for the atroposelective synthesis of 4‐arylquinolones by the chiral–ligand‐controlled generation of a chiral axis. The solvent (HFIP) and the substitution on the N atom of the cinnamide have an important impact on the enantioselectivity obtained. DFT studies have provided insight into the mechanism, showing that the reaction proceeds via prior activation of the alkene, and the enantioselectivity is determined during the β‐hydride elimination step.