Lewis acid mediated three-component one-flask regioselective synthesis of densely functionalized 4-amino-1,2-dihydropyridines via cascade Knoevenagel/Michael/cyclization sequence

A highly convergent and regioselective one-pot synthesis of hitherto unreported 4-amino-1,2-dihydropyridines has been achieved via three-component domino coupling (3CDC) of alpha-oxoketeneN,S-arylaminoacetals, aldehydes, and malononitrile in the presence of InCl3 under solvent-free conditions. The merit of this cascade Knoevenagel condensation/Michael addition/cyclization sequence is highlighted by its atom-economy, efficacy of forming consecutive three new bonds (two C-C and one C-N), and one ring in a single operation. Noteworthy, the presence of nitrile and amino groups at 3- and 4-positions of 1,2-dihydropyridine ring makes these compounds excellent precursors for further synthetic renovations. Remarkably, one of the newly synthesized 4-amino-1,2-dihydropyridine exhibited high selectivity and sensitivity for Fe3+ ion over other metal ions. (C) 2014 Elsevier Ltd. All rights reserved.