Mechanistic Exploration of Umpolung Guided Stetter‐Aldol Reaction and Its Dependence on the Choice of Imine

Abstract

AbstractNHC‐catalyzed Stetter‐aldol reaction for the synthesis of hydroxyindanone takes place via umpolung reactions of phthalaldehyde followed by intramolecular aldol reaction when N‐tert‐butoxycarbonyl (Boc) imine is used and this leads to the formation of [4+1] annulation product. However, this mechanism doesn't follow similar sequence in case of N‐tosyl‐α,β‐unsaturated ketimine and [4+2]‐annulation product is found as the sole product for the latter case through formation of aza‐“Berslow intermediate”. In this study we have used state of the art computational techniques to find out the possible reason for the difference in product and the detailed mechanistic pathway for the above two reactions. Thus, we explain the mechanism for obtaining the selective annulation product ([4+1] vs [4+2]) that can help chemists to design and synthesize a new series of compounds.