Unlocking Azulene Functionalization via Strain-Induced Azulyne Intermediates

Azulene, a nonbenzenoid aromatic isomer of naphthalene with exceptional optoelectronic properties, has long eluded general methods for selective functionalization, especially on its electron-deficient seven-membered ring. Here, we overcome this limitation by introducing the first practical precursors to azulyne intermediates. In stark contrast to well-established benzyne chemistry, the synthesis of these azulyne precursors is far from trivial, demanding tailored strategies to construct their bicyclic frameworks. Computations reveal that 5,6- and 4,5-azulyne possess substantial yet manageable ring strain and marked electrophilicity. Leveraging these versatile intermediates, we develop a modular platform that enables direct, efficient, and site-selective incorporation of diverse functionalities onto the azulene core through cycloadditions, nucleophilic additions, σ-bond insertions, and transition-metal-catalyzed reactions. This strategy grants unprecedented access to a wide range of polysubstituted azulenes and complex azulene-embedded polycyclic aromatic compounds (PACs), with regioselectivity governed by predictable steric and electronic principles. Our work transforms azulene from a synthetically challenging motif into a programmable building block based on this unique nonalternant architecture.