Asymmetric Synthesis of Trifluoromethyl-Containing Spiro[indoline-3,2′-pyrrolidine]s by Organocatalytic Cycloaddition

Abstract

The unique biological activity of pyrrolidine compounds has attracted significant interest from medicinal chemists. This study presents a one-step synthesis of [indolyl-3,2′-pyrrolidine] compounds with three chiral centers and an α-CF₃ group in excellent yields and enantioselectivities by reacting trifluoroethyl ketoimine with unsaturated alkynyl ketone compounds by a chiral-guanidine-catalyzed [3+2] cycloaddition reaction. The mild reaction conditions, low catalyst loading, and high reaction rate make this synthetic method highly attractive for pharmaceutical synthesis.

Key words

asymmetric synthesis - trifluoromethyl-containing compounds - guanidine catalysis - spiropyrrolidines - [3+2] cycloaddition reaction

Publication History

Received: 15 January 2025

Accepted after revision: 10 April 2025

Accepted Manuscript online:
10 April 2025

Article published online:
08 May 2025

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