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

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.