Zinc (II)-Mediated Selective O-Benzylation of 2-Oxo-1,2-Dihydropyridines Systems

Abstract

The selective O-benzylation of 2-oxo-1,2-dihydropyridines plays a critical role in organic synthesis of natural products and biological active molecules. Herein we report a novel ternary system of ZnO, ZnCl2 and N,N-diisopropylethylamine (DIEA), that is highly effective for selective O-benzylation of 2-oxo-1,2-dihydropyridines using abundant substituted benzyl halides and related substituted 2-oxo-1,2-dihydropyridines compounds. This process allows access to a variety of O-benzyl products under mild reaction conditions, which are important synthetic intermediates in the protection of functional groups, and represents a new method toward the development for the O-benzylation of 2-oxo-1,2-dihydropyridines.

Pd-Catalyzed Chemoselective O-Benzylation of Ambident 2-Quinolinone Nucleophiles

“…Most approaches rely on the silver salt method, derived originally from the century-old Koenigs–Knorr reaction to synthesize O-glycosides, developed by Tieckelmann over 50 years ago to selectively O-alkylate heterocyclic ambident heterocyclic anions using stoichiometric amounts of Ag 2 CO 3 . Since that time, little progress has been made and only sparse reports of methods that obviate the need of Ag-salts for selective O-alkylation, albeit with very limited substrate scope, have appeared in the literature. ,,− More specifically, a general chemoselective O-alkylation of ambident 2-quinolinones without the use of Ag-salts, to the best of our knowledge, is unprecedented. We are aware of a recent report of a proposed Pd-catalyzed O-benzylation of 2-pyridones in the presence of stoichiometric Ag-salts .…”