Inter‐Cage Na ⁺ Enabling Single‐Atom Co for In Situ Delivery of Bio‐Based Vinyl Backbone to Access 3,4‐Unsubstituted Quinolines

ABSTRACT

The multi‐step access to versatile N‐heterocyclic scaffolds is highly dependent on non‐renewable fossil‐based feedstock over different catalysts for each step. Here, a mesoporous NaY zeolite‐encapsulated atomically dispersed cobalt catalyst (Co@NaY‐M) is deliberately designed to be robust for single‐step, three‐component upgrading of biomass‐derived lactic acid, aldehydes, and anilines into 3,4‐unsubstituted quinolines via cascade dehydrogenation, annulation–aromatization, and decarboxylation. Na ⁺ co‐dopant in zeolitic hexagonal prism adjacent to single‐atom Co in the supercage acts as an electron promoter to pull electrons from Co. The electron‐deficient Co improves formed intermediate adsorption/activation, significantly declining energy barriers in cascade lactic‐acid‐to‐vinyl‐intermediate dehydrogenation, and 4‐substituted quinoline decarboxylation. Meanwhile, the presence of Na ⁺ strengthens interactions between Co and zeolitic carrier to improve the single‐atom stability. Co@NaY‐M has broad substrate scope for various 3,4‐unsubstituted quinolines with good compatibility to diverse functional groups in yields reaching 98% (>80 examples) and can be scaled up (11.24 g). Importantly, the developed methodology enables direct synthesis of various clinical drugs. Life‐cycle/techno‐economic investigations indicate that this protocol markedly lessens environmental footprints and is more price‐competitive compared to conventional quinoline synthesis methods. The precise modulation of neighboring zeolitic sites provides an effective avenue to directly access high‐value nitrogenous heterocycles from abundant renewables via oriented multiple reactions.