C-H Activation and Cross-Coupling of Acyclic Aldonitrone

Palladium-catalyzed activation of C(sp(2))-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.

Automated summary

The palladium-catalyzed activation of C(sp(2))-H bond in an easily E,Z-isomerizable aldonitrone with an ester group at the C terminus enabled its cross-coupling with various aryl and heteroaryl bromides to produce ketonitrones. The reactions exhibited high E selectivity and the use of sterically hindered carboxylic acid as an additive, along with a non-polar solvent like toluene, was crucial for achieving good yields of the cross-coupling products. The obtained ketonitrones were further shown to be useful in dipolar cycloaddition or nucleophilic addition reactions.