“On water” metal-free direct C–H amination and imination of olefins via tandem SNAr, click chemistry, and molecular nitrogen release

Abstract

We report a metal-free, sustainable C–H amination method conducted in an aqueous environment. This method leverages a combination of tandem nucleophilic aromatic substitution, metal-free click reactions, and de-nitrogenation processes, all facilitated by the hydrophobic effect of water. Specifically, perfluo(hetero)aryl compounds undergo azidation, followed by a 1,3-cycloaddition with olefins and nitrogen evolution reactions on the hydrophobic surface of water, yielding the desired amine or imine products. The resulting structures hold significant potential in medicinal chemistry and agrochemicals. This approach obviates the need to isolate unstable and potentially explosive perfluoro-azides and circumvents the pre-functionalization of olefins. Utilizing water as a solvent replaces toxic organic solvents and mitigates safety concerns associated with handling azides. Our method exhibits high selectivity and efficacy across a broad spectrum of perfluoroarenes and olefins. Detailed mechanistic studies reveal the formation of a 1,2,3-triazoline adduct as a reactive intermediate, which subsequently converts into the final product via the elimination of nitrogen gas.