PPh ₃ -Promoted Remote ε′,ε′-Regioselective (4 + 1) Annulation of Pyrrolidinone-Based MBH Carbonates with 1-Heterodienes to Access Highly Substituted 1,6-Diazaspiro[4.4]nonenes

An efficient and remote ε′,ε′-regioselective (4 + 1) annulation reaction between pyrrolidinone-based Morita–Baylis–Hillman (MBH) carbonates and 1-heterodienes was pioneered in the presence of triphenylphosphine (PPh3). This approach enables the facile synthesis of a wide variety of highly substituted 1,6-diazaspiro[4.4]nonenes bearing bis-N-substituted quaternary carbon centers, achieving high yields (up to 90%) along with excellent regioselectivities. Moreover, the practical applicability of this methodology is substantiated by its successful implementation in subsequent synthetic transformations and the late-stage functionalization of drug molecules. Additionally, a molecular docking study was carried out to explore the potential biological activities of the synthesized products.