Beyond Push-Pull Chromophores: Unlocking the Synthetic Potential of Formal [2+2] CA-RE for Quinolone Annulation

The donor-acceptor [2+2] cycloaddition-retro-electrocyclization (CA-RE) reaction is a cornerstone of push-pull chromophore synthesis, yet its broader potential in synthetic methodology remains largely untapped. Here, we repurpose classical CA-RE chemistry as a metal-free annulation strategy by intercepting the formal CA-RE intermediate through an intramolecular nucleophilic cyclization cascade. Readily available o-aminophenyl alkynes react with in situ or ex situ generated dicyanoalkenes to afford dicyanovinyl-substituted dihydroquinolines, which are efficiently converted by sequential oxidation and dehydrogenation into structurally diverse, medicinally important quinolin-4-ones. The protocol accommodates hydrogen, alkyl, and aryl substitution patterns while retaining the operational simplicity of classical CA-RE chemistry. The resulting 4(1H)-quinolinones provide versatile intermediates for concise access to pharmacologically relevant quinolines through well-established one-step transformations. Isolation of a cyclobutene intermediate supports the involvement of the canonical CA-RE pathway prior to annulation. The synthetic utility of the method is demonstrated by the concise synthesis of the natural product 2-propyl-4(1H)-quinolinone. Beyond providing an efficient route to quinolin-4-ones, this work establishes classical donor-acceptor CA-RE chemistry as a versatile platform for annulation and heterocycle synthesis.