Expedient, catalyst-free, three-component synthesis of fused tetrahydropyridines in water

摘要

A catalyst-free, three-component reaction between amino alcohols, 1,3-dicarbonyl compounds and alpha, beta-unsaturated aldehydes was developed for the synthesis of fused tetrahydropyridines in water. The beta-enaminone formation-initiated domino sequence afforded oxazolo[3,2-a]pyridines and pyrido[2,1-b] [1,3]oxazines diastereoselectivity in good yields involving Michael addition, intramolecular cyclization and iminium ion cyclization steps. This environmentally benign protocol is highly atom-economical where the only side product was two molecules of water and no catalyst or reagent was employed. Besides, in a single operation, four new bonds including two C-N, one C-O and one C-C bonds and two heterocyclic rings were created. The reaction was also effective in various green solvents such as glycerol, PEG-200 and lactic acid.