Base‐Catalyzed Domino Isomerization/Oxidant‐Free Dehydrogenative Annulation of Allylic Alcohols: Scope, Mechanism, and Application

Abstract

AbstractA domino reaction comprising four consecutive steps based on the strategy of isomerization of allylic alcohols was developed. This base‐catalyzed protocol provided an approach for constructing polysubstituted quinolines without additional additives. A wide range of di‐ or trisubstituted γ‐aminoaryl allylic alcohols bearing alkyl or (hetero)aryl substituents were transformed to a range of structurally diverse quinolines. The utility of this transformation was demonstrated by the application in the concise synthesis of several polysubstituted quinoline derivatives, including natural products and pharmacological agents. Preliminary mechanistic experiments suggest that the isomerization of γ‐aminoaryl allylic alcohol proceeds via an intramolecular 1,3‐hydrogen shift whereas for the aromatization of the dihydroquinoline intermediate two possible pathways exist: acceptorless dehydrogenation and transfer hydrogenation.