NH4OAc-Promoted Domino Route to Hydroxyarylated Unsymmetrical Pyridines under Neat Conditions

Abstract

A new metal-, oxidant-, and solvent-free ecofriendly domino method has been established for modular synthesis of a diverse range of medicinally promising hydroxyarylated unsymmetrical pyridines in good to high chemical yields with an excellent regioselectivity. This domino process involves a range of N-sulfonyl ketimines as C,N-binucleophiles, enolizable ketones, and aromatic/heteroaromatic aldehydes using ammonium acetate as an ideal promoter under neat conditions, which creates two new C-C bonds and one C-N bond. Notably, the neutral reaction conditions are mild enough to tolerate a range of functionalities and cover a variety of substrates, thus bestowing a powerful avenue to access tri- A nd tetrasubstituted pyridines including carbo- A nd heterocyclic fused ones. Interestingly, a practical, scalable, and high-yielding synthesis of pyridylphenol derivatives was successfully accomplished by our unique method. © 2019 American Chemical Society.