Base-Promoted Cycloisomerization for the Synthesis of Indolizines and Related Heterocycles

The base-mediated 5-exo-dig type cyclization reaction of homopropargyl pyridines for the construction of indolizines has been reported for the first time. A variety of indolizine derivatives could be obtained in moderate to excellent isolated yields by treatment of homopropargyl pryidines with cesium carbonate in DMSO at 100 degrees C. This strategy could also be adapted to the synthesis ofpyrrolo[1,2-a] quinolines and pyrrolo[1,2-a]pyrimidines from the corresponding homopropargylquinolines and homopropargylpyrimidines, respectively. The mechanism involves alpha C-H deprotonation, 5-exo-dig cyclization, and isomerization of the exocyclic double bond to provide the heteroaromatic system. The transformation reported herein does not require the aid of transition metal catalysts or halogens, and is thus environmentally friendly.