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. 2025 Apr 30;15(1):15174.
doi: 10.1038/s41598-025-97860-0.

One-pot three-component synthesis of azaspirononatriene derivatives

Ali Oudi  1 , Abbas Ali Esmaeili  2 , Azizollah Habibi  3
Affiliations

One-pot three-component synthesis of azaspirononatriene derivatives

Ali Oudi et al. Sci Rep. .

Abstract

The present investigation has introduced a new class of isocyanide/acetylene-based multicomponent reactions (IAMCRs). These are a robust technique for efficiently synthesizing intricate spiro architectures through a zwitterionic adduct. The coupling reaction between the "in situ" generated dipoles of the isocyanide-acetylenic ester adducts and 3-alkyl-4-arylidene-isoxazol-5(4H)-one derivative presents a highly effective synthetic pathway for obtaining novel 1-oxo-2-oxa-3-azaspiro[4.4]nona-3,6,8-triene heterocycles. The broad range of substrates, standard experimental conditions, straightforward procedure, and impressive yields make our catalyst-free three-component approach highly practical and green, as it remarkably offers step-, time- and cost-effectiveness based on the green metrics.

Keywords: 1-Oxo-2-oxa-3-azaspiro[4.4]nona-3,6,8-triene; 4-Arylidene-isoxazol-5(4H)-one; Based multicomponent reaction; Isocyanide; Spiro heterocycle; Three-component reaction.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This article does not contain any studies with human participants or animals performed by the authors.

Figures

Fig. 1
Fig. 1
Synthetic Versatility of 4-Arylideneisoxazolone-Based Spiro Heterocycles.
Fig. 2
Fig. 2
ORTEP structure of product 4k.
Fig. 3
Fig. 3
The probable mechanism for the formation of products 4.
Fig. 4
Fig. 4
Evaluation of IAMCR approach employed for the synthesis of 4a-n by the green filters’ metrics of AE, E-factor, RME and PMI in terms of its efficiency, sustainability and environmental impact.
See this image and copyright information in PMC

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