Palladium(ii)-catalyzed intramolecular C–H amination to carbazole: the crucial role of cyclic diacyl peroxides

Abstract

Despite extensive efforts in metal-free synthesis, strained cyclic diacyl peroxides have not been invoked as external oxidants in high-oxidation state palladium-catalyzed reactions and their involvement in the corresponding elementary steps has not been studied. Herein, a Pd^II-catalyzed intramolecular oxidative C–H amination has been successfully developed for the construction of carbazole architectures under additive-free and mild conditions. The presented method proved to be compatible with a variety of functional groups and scalable synthesis, which enabled the late-stage diversification of bioactive molecules and facilitated the concise syntheses of carbazole alkaloid derivatives. Importantly, the use of strained cyclic diacyl peroxides as a sacrificial oxidant is critical for controlling the reactivity of high-valent Pd intermediates and their selectivity to multiple competing reductive elimination events, owing to the rigid constraint imposed by the bidentate dicarboxylate ligand. Mechanistic studies suggested that this reaction proceeds via a unique Pd^II/Pd^IV catalytic pathway, and the turnover-limiting step is substrate coordination to the palladium catalyst. Moreover, photophysical investigation showed that varying N-protecting groups and increasing conjugated systems had a clear influence on the photophysical properties of carbazole derivatives. The calculation of six green metrics demonstrates the latent greenness of this catalytic system.