DBU‐Promoted Intramolecular Crossed Aldol Reaction: A Facile Access to Indane‐Fused Pyrrolidine

Abstract

A new strategy for the facile synthesis of indane‐fused pyrrolidines through DBU‐promoted intramolecular crossed aldol reaction has been developed. The efficiency, compatibility and practicality of this method were demonstrated by a broad substrate scope, mild reaction conditions and gram‐scale synthesis. The further derivatizations of the synthesized diastereoisomers 2a and 2a′ were performed for arylation, alkenylation, amination and etherification, showing high diastereoselectivities. Deuterium labeling experiment suggests a possible carbocation process which leads to the high diastereoselectivity during the transformations of 2a and 2a′ . Based on this strategy, the 5‐HT 2C agonist V and the antihypertensive agent VI were successfully synthesized through a three‐step synthetic pathway. This new strategy potentially enables a wide exploration of these indane‐fused derivatives applied for pharmaceuticals and related fields.