The lateral lithiation of pyrazoles: direct, transition-metal-free access to pyrazolopyridinones and pyrazolopyranones

Abstract

Lateral lithiation of amidopyrazoles enables an expedient, modular, transition metal-free synthesis of pharmaceutically relevant pyrazolopyridinones and pyrazolopyranones via reaction with nitriles or esters, respectively. The reactions are amenable to alkyl or (het)aryl groups at C-6 and N-1. Secondary amide and nitrile directing groups give access to N-5 alkyl and C-4 amino substitution, and functionalization of the C-3 and C-7 positions of the pyrazolopyridinones is also feasible. 2-Cyanopyridines and dinitriles furnish products with potential as ligands for transition metals.