Aerobically-initiated C(sp3)–H bond amination through the use of activated azodicarboxylates

Abstract

Significant advancements in C–N bond formation via C–H bond functionalisation have made it a staple in the production of nitrogen-containing compounds in both industry and academia. However, transition metal-free synthesis, particularly in the case of C(sp³)–N formation, has remained a significant challenge to the synthetic community. Herein we report a procedure for α-C(sp³)–H amination of ethereal compounds through use of azodicarboxylates as the nitrogen source and freely-available atmospheric oxygen to access ethereal radical intermediates via aerobic C–H activation. The use of fluorinated alcohols as solvent is observed to greatly increase the efficiency of the reaction and we show experimentally and theoretically the key role of H-bonding between fluorinated alcohols and azodicarboxylates. Calculations of the condensed Fukui functions of a H-bonded fluorinated alcohol-azodicarboxylate complex correlates with a significantly increased susceptibility of azodicarboxylates to undergo reaction with radicals, which informs a number of recent reports in the literature.