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

ABSTRACT

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.