Base‐Promoted Annulation for the Synthesis of Functionalized Isoxazole‐Linked 1,4‐Dihydropyrazolo4′,3′:5,6pyrano2,3‐ b Quinolines

ABSTRACT The development of efficient synthetic procedures for pharmacophore combinations remains a central goal in synthetic chemistry. Herein, a novel series of isoxazole‐linker‐based 1,4‐dihydropyrazolo4′,3′:5,6pyrano2,3‐ b quinolines has been synthesized via a metal‐free transformation between 3‐methyl‐4‐nitro‐5‐(2‐(haloquinolin‐3‐yl)vinyl)isoxazole and pyrazolones under reflux conditions in ethyl acetate using triethylamine as a base, providing 33 examples in up to 94% yield. This mechanistic process, involving a 1,6‐Michael addition and subsequent S N Ar route, provides a feasible and inspiring strategy for fabricating more complex architectures. Based on this platform, an enantioselective synthesis of several chiral target compounds has also been accomplished using a quinine‐derived thiourea catalyst (20 mol%), affording 12 target products with up to 96% ee and moderate yield.