Hydrogen-Bonding Network-Enabled Terminal Selective Heteroarylation of Allenamides in Hexafluoroisopropanol

Abstract

Hexafluoroisopropanol (HFIP)-mediated terminal selective heteroarylation of allenamides has been accomplished through H-bonding network-enabled substrate activation in a robust fashion. This strategy features a cascade process involving sequential nucleophilic addition followed by electrophilic heteroaromatic substitution and is well suited for late-stage functionalization of complex bioactive molecules. The elucidation of the underlying mechanism was achieved through a comprehensive combination of several control experiments, kinetic studies, isotopic labeling experiments, and the isolation of the HFIP-allenamide intermediate adduct.