Site-Selective Electrophilic Cyclization and Subsequent Ring-Opening: A Synthetic Route to Pyrrolo[1,2‑<i>a</i>]quinolines and Indolizines

Abstract

An efficient strategy for the synthesis of pyrrolo­[1,2-<i>a</i>]­quinolines and indolizines from pyranoquinolines via site-selective electrophilic cyclization and subsequent opening of pyran ring using silver/iodine under mild reaction conditions is described. This approach involves the preferential attack of the pyridyl nitrogen over aryl ring and leads to the formation of 5-<i>endo</i>-<i>dig</i> cyclized products. Quantum chemical calculations between C–N (Δ<i>E</i>_a = 9.01 kcal/mol) and C–C (Δ<i>E</i>_a = 31.31 kcal/mol) bond formation were performed in order to rationalize the observed site selectivity. Structure of the products were confirmed by the X-ray crystallographic studies. Iodo-substituted compounds generated by the electrophilic iodocyclization were further diversified via Pd-catalyzed cross-coupling reactions