Amine-Catalyzed [3+3] Annulation Reaction Between α-Alkylidene Pyrazolinones and α,β-Unsaturated Aldehydes for the Construction of Spiropyrazolones

Abstract

A secondary amine-catalyzed [3+3] annulation of α-alkylidene pyrazolinones with α,β-unsaturated aldehydes was reported. Conducted in ethanol with acetic acid as an additive, the reaction proceeds at room temperature under a nitrogen atmosphere, affording a series of spirocyclohexane pyrazolinone compounds in high yields (up to 96%) and excellent diastereoselectivity (dr up to 99:1). Gram-scale amplification experiments show that the yield and diastereoselectivity remain uncompromised, highlighting the significant application potential of this synthetic protocol. HR-MS-based mechanistic studies confirm that the reaction follows a Michael-Aldol cascade pathway.

Keywords

Amine catalyst - α-Alkylidene pyrazolinone - α,β-Unsaturated aldehydes - [3+3] Annulation - Spirocyclic compound

Data Availability Statement

The data underlying this study are available in the published article and its online Supporting Information.

Publikationsverlauf

Eingereicht: 12. November 2025

Angenommen nach Revision: 15. Dezember 2025

Accepted Manuscript online:
16. Dezember 2025

Artikel online veröffentlicht:
30. Dezember 2025

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