Iodine catalyzed mild 4CR protocol for synthesis of Tetrahydroimidazo[1,2-a]pyridines: cascade construction of multiple C-C and C-Hetero bonds

A highly convergent and straight forward synthesis of N-fused heterocycles, including 1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-5-carboxylic acids is successfully achieved via a one-pot four-component cascade reaction utilizing pyruvic acid, aldehydes, diamines and 1,1-bis(methylthio)-2-nitroethylene (BMTNE) in the presence of a catalytic amount of molecular iodine in acetonitrile. The new efficient domino protocol generates two rings by the concomitant formation of C-N (three) and C-C (two) multiple bonds presumably involving a sequence of N,N-acetal formation, Knoevenagel reaction, aza-ene reaction, imine-enamine/keto-enol tautomerization, and N-cyclization as key steps. The merit of this protocol is highlighted by its easily available and economical starting materials, operational simplicity, efficient utilization of all the reactants, clean reaction profile, simple workup procedure, and tolerance of a wide variety of functional groups.

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