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- and tetrasubstituted pyridines including carbo- and heterocyclic fused ones. Interestingly, a practical, scalable, and high-yielding synthesis of pyridylphenol derivatives was successfully accomplished by our unique method.

Sustainable Four-Component Annulation for the Synthesis of 2,3,4,6-Tetraarylpyridines

“…On the basis of previous literature reports, ,, two possible reaction pathways are proposed as shown in Scheme . In path a , Knoevenagel condensation of diaryl ethanone 3 and aldehyde 2 leads to the formation of chalcone A .…”

“…10 Very recently, Samanta et al reported the synthesis of unsymmetrical pyridines from N-sulfonyl ketimines, aromatic aldehydes, and ammonium acetate under neat conditions. 11 Consequently, it is still desirable to explore new, efficient methods for the construction of unsymmetrically multisubstituted pyridines.…”

“…However, this condensation usually gives symmetrically substituted pyridines, typically 2,4,6-trisubstituted pyridines. − , Only a few reports demonstrate the synthesis of unsymmetrically multisubstituted pyridines up to now, for example by condensation of 3-oxopropanenitriles or 1,3-diones with an aromatic aldehyde, a ketone, and a “N” source . Very recently, Samanta et al reported the synthesis of unsymmetrical pyridines from N -sulfonyl ketimines, aromatic aldehydes, and ammonium acetate under neat conditions . Consequently, it is still desirable to explore new, efficient methods for the construction of unsymmetrically multisubstituted pyridines.…”