Zn(II)-Catalyzed Multicomponent Sustainable Synthesis of Pyridines in Air.

Abstract

Herein, we report a Zn(II)-catalyzed solvent-free sustainable synthesis of tri- and tetra-substituted pyridines using alcohols as the primary feedstock and NH4OAc as the nitrogen source. Using a well-defined air-stable Zn(II)-catalyst, 1a, featuring a redox-active tridentate azo-aromatic pincer, 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline (La), a wide variety of unsymmetrical 2,4,6-substituted pyridines were prepared by three-component coupling of primary and secondary alcohols with NH4OAc. Catalyst 1a is equally compatible with the four-component coupling. Unsymmetrical 2,4,6-substituted pyridines were also prepared via a four-component coupling of a primary alcohol with two different secondary alcohols and NH4OAc. A series of tetra-substituted pyridines were prepared up to 67% yield by coupling primary and secondary alcohols with 1-phenylpropan-1-one or 1,2-diphenylethan-1-one and NH4OAc. The 1a-catalyzed reactions also proceeded efficiently upon replacing the secondary alcohols with the corresponding ketones, producing the desired tri- and tetra-substituted pyridines in higher yields in a shorter reaction time. A few control experiments were performed to unveil the mechanistic aspects, which indicates that the active participation of the aryl-azo ligand during catalysis enables the Zn(II)-complex to act as an efficient catalyst for the present multicomponent reactions. Aerial oxygen acts as an oxidant during the Zn(II)-catalyzed dehydrogenation of alcohols, producing H2O and H2O2 as byproducts.