Cascade Annulation for Synthesizing Chromenopyrrolones from o‑Hydroxyphenyl Enaminones and 2‑Halo‑N‑alkyloxyacetamides

• Published in: Journal of organic chemistry 2024-12, Vol.89 (24), p.18322-18336
• Main Authors: Zhang, Wei-Min, Zhao, Qing-Sheng, Chen, Si-Yi, Zhang, Cong-Hai, Yan, Sheng-Jiao
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/acs.joc.4c02154

A cascade cyclization reaction comprising two halogenation reactions and a Michael addition was developed for the synthesis of chromeno­[2,3-c]­pyrrole-3-ones 4. Additionally, another cascade cyclization reaction, which involves a halogenation reaction followed by two intramolecular Michael additions, was established for the synthesis of chromeno­[2,3-b]­pyrrole-2-ones 5. Both types of compounds were synthesized from o-hydroxyphenyl enaminones and 2-halo-N-alkyloxyacetamides through a process that facilitated the intramolecular formation of C–C, C–O, and C–N bonds to effectively establish two fused rings in a single operation. This novel protocol is efficient, uses readily accessible starting materials, and operates under mild conditions, demonstrating tolerance for various functional groups while achieving good yields.