Iron-Promoted Ring Opening and Ring Closing Cascade (ROCC) Reaction of C3-(2-(Phenylethynyl)phenyl)isoxazoles Leading to 3-Amino-1,3-diphenylpropenone and Isoindolin-1-ylidene Derivatives

Abstract

An efficient direct synthetic approach to functionalized isoindolin-1-ylidene derivatives has been developed via FeCl₃/Li₂CO₃-mediated isoxazole cleavage. The resulting novel scaffolds represent valuable chemotypes of growing significance in medicinal chemistry and the pharmaceutical industry. The highlight of the work is the sequential reductive ring opening of C3-(2-(phenylethynyl)phenyl)ortho-alkynyl-isoxazole and intramolecular 5-exo-dig cyclization of ortho-alkynyl-isoxazole. Additionally, we reported that Fe/NH₄Cl could be used to generate 3-amino-1,3-diphenylpropenone from isoxazole. Using this protocol, densely substituted N-heterocyclic compounds can be assembled in a simple and efficient manner. This is the first report on the synthesis of isoindolin-1-ylidene derivatives using FeCl₃/Li₂CO₃ and using isoxazole as starting material.

Keywords

Ring opening - Ring closing - Isoindolin-1-ylidene - 3-Amino-1,3-diphenylpropenone derivatives - Ortho-alkynyl-isoxazoles - FeCl₃ - Li₂CO₃

Publication History

Received: 04 September 2025

Accepted after revision: 17 October 2025

Accepted Manuscript online:
17 October 2025

Article published online:
26 November 2025

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