Palladium‐catalyzed activation of C(sp2)−H bond in a readily E,Z‐isomerizable aldonitrone, bearing an ester group at the C terminus, enabled its cross‐coupling with a variety of aryl and heteroaryl bromides to give ketonitrones, including products with functional groups not compatible with the classical nitrone synthesis via condensation with hydroxylamines. The reactions proceeded with very high (usually complete) E selectivity. The key to obtaining good yields of the cross‐coupling products was the use of sterically hindered carboxylic acid as additive and non‐polar solvent (toluene), in which the starting nitrone exists mainly as E isomer. Further use of the obtained ketonitrones in dipolar cycloaddition or nucleophilic addition has also been demonstrated.