Synthesis of Spiro-ß-lactam-pyrroloquinolines as Fused Heterocyclic Scaffolds through Post-transformation Reactions.

ABSTRACT

A sequential post-transformation of Ugi four-component reaction/nucleophilic substitution was developed for the synthesis of spiro-ß-lactam-pyrroloquinolines. This method involves the Ugi-4CR of 2-chloro-3-formyl quinolines 1a-h, amines 2a-d, 2-chloroacetic acid 3, and isocyanides 4a, 4b for the synthesis of versatile precursors 5a-v. The Ugi adducts were intramolecularly cyclized under basic conditions through the sequential nucleophilic aromatic substitution (SNAr)/second-order nucleophilic substitution (SN2) reaction to give spiro-ß-lactam-pyrroloquinoline scaffolds 6a-t. This approach is an efficient method for the synthesis of fused bioactive heterocyclic backbones containing quinoline, pyrrolidone, and ß-lactam with high bond-forming efficiency.