InCl3-Assisted Eco-Friendly Approach for N-Fused 1,4-Dihydropyridine Scaffolds via Ring Opening Michael Addition of Cyclic Nitroketene and Iminocoumarin: Synthesis and DFT Studies

A novel strategy was developed for the synthesis of five different N-fused 1,4-dihydropyridine (1,4 DHP) scaffolds such as imidazopyridine, pyridopyrimidine, benzoimidazopyridine, thiazolopyridine and benzopyridooxazine derivatives by coupling nitroketene S,S-acetal, various nitrogen containing dinucleophiles, malanonitrile and substituted salicylaldehydes/aldehydes in the presence of InCl3 as catalyst in water-EtOH solvent mixture under reflux condition. Furthermore, mechanism for the formation of 1,4-DHPs was explored through experimental and DFT calculations. DFT studies reveal that the reaction went through lower energy triheterocyclic intermediate than the higher energy chromenoimidazopyridine imtermediate. The attractive features of this protocol include short reaction time, easy separation of the product without chromatographic purification, simple execution with excellent yield and possibility to synthesize structurally diverse 1,4-dihydropyridine derivatives through greener approach.