Сross-dehydrogenative C-O coupling of oximes with hydrazones: synthesis of fungicidal azo oxime ethers

Abstract

The cross-dehydrogenative coupling (CDC) of oximes with hydrazones employing KMnO 4 as the oxidant was discovered.Presumably, the reaction proceeds through the selective cross-recombination of oxime and hydrazone-derived free radicals despite the fact that both of them are known to undergo self-coupling and other processes with C-C, C-O, C-N, and N-N bond formation. The proposed approach is general and applicable to a broad range of oximes and hydrazones. Previously, oxime derived radicals were mainly involved in intramolecular processes of C-O bond formation, while intermolecular processes remained rare and their scope was limited. On the other hand, radical functionalization of hydrazones was generally limited to radical addition and hydrogen substitution reactions of aldehyde hydrazones. The formation of azo compounds in the present work represents a distinctive direction for further development. The synthesized compounds exhibited pronounced fungicidal activity against a wide spectrum of phytopathogenic fungi (Venturia inaequalis, Rhizoctonia solani, Fusarium oxysporum, Fusarium moniliforme, Bipolaris sorokiniana, Sclerotinia sclerotiorum) in some cases surpassing the activity of commercial fungicides triadimefon, krezoxim-methyl, and azoxystrobin. Key factors contributing to the high fungicidal activity were identified as the presence of a small aliphatic substituent at the C-O coupling site and electronwithdrawing substituents in the oxime moiety.