Organocatalytic Modified Guareschi–Thorpe Type Regioselective Synthesis: A Unified Direct Access to 5,6,7,8-Tetrahydroquinolines and Other Alicyclic[b]‑Fused Pyridines

An unprecedented organocatalytic, regioselective, modified Guareschi–Thorpe type protocol toward the modular synthesis of 5,6,7,8-tetrahydroquinolines 22a–g and other alicyclic­[b]-fused pyridines 23–28 via the identification of Chitosan as a heterogeneous catalyst is reported. This novel strategy is operationally simple and showed a wide range of functional group tolerance and substrate compatibility. The proposed mechanistic pathway involves an imine-enamine cascade approach for the synthesis of structurally diverse alicyclic­[b]-fused pyridine heterocycles. The gram scale synthesis and identification of a new class of antifungal molecules 29–31 emphasize the practicality of this method.