Triple C–F bond functionalization via an orderly elimination–oxidation–substitution relay reaction

Abstract

A primary challenge in defluorinative functionalization of readily accessible trifluoromethyl reagents is exhaustive defluorination caused via repetition of the same reaction where the C–F bond strength decreases sequentially during defluorination. In this work, we introduced a novel comovement group (CG) strategy where the cleavage of each C–F bond occurs through different reactions initiated by distinct CGs, rather than by direct activation of the C–F bond, thus enabling an orderly and diversified triple C–F bond functionalization reaction. The reaction provides straightforward access to a wide range of α-ketoamides and quinoxalinones from readily available trifluoromethyl diazo compounds and amines under mild conditions using water and oxygen in air as oxygen atom sources. This method features high bond formation efficiency (two CO bonds and one C–N bond in one-pot), exceptionally high regio- and chemoselectivities, and broad functional group compatibility, including alkyl and aryl amines, amino acids, peptides, and drug-like molecules. The emergent principle outlined herein provides guidelines to inspire further research endeavors in fluorine chemistry with both exceptional precision and generality.