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

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.