Functionalization of N-tosyl-2-pyridinone with silyl ketene acetalcatalyzed by Lewis acid, and synthetic studies of corynantheidol

Abstract

The reaction of N-tosyl-2-pyridinone with tert-butyldimethylsilyl ketene acetal, catalyzed by a Lewis acid, has been investigated. While both the C-4 Michael adduct 3 and the bicyclic compound 5 were isolated from aluminum chloride- or trimethylaluminum-catalyzed reactions, the former was afforded as the sole product from diethylaluminum chloride- or trimethylsilyl trifluoromethanesulfonate-catalyzed reactions. During investigation of a synthesis of corynantheidol, a method for construction of the key intermediate 30 was accomplished via, (1), the efficient conversion of the enamine moiety to an alkenyl bromide (20→22), followed by the Sonogashira coupling reduction (22→23); (2), selective reduction of the acetylene and intramolecular cyclization (25→26); (3), the coupling reaction with the indole unit (27→30).