Construction of Carbazoles from 2-Bromobiaryls Using N₂ as a N Source

Abstract

Due to the high activation barriers associated with cleaving both C–H bonds and the N≡N triple bond, achieving C–N bond formation from relatively inert C–H bonds as carbon sources under mild conditions has long posed a major challenge in synthetic chemistry. To address this long-standing issue, we have developed a novel and straightforward approach for the synthesis of carbazoles, using N₂ as the nitrogen source and 2-bromobiaryls as the carbon partner through an engineered one-pot/two-step protocol. The key to this protocol lies in the in-situ generation of lithium nitride (Li₃N) from N₂ using lithium as the reductant, which serves as a primary intermediate. This intermediate then undergoes a Pd-catalyzed process involving successive C(sp²)–Br bond activation and intramolecular C(sp²)–H bond functionalization to form the target carbazole framework. Notably, this strategy exhibits a broad substrate scope, excellent tolerance towards various functional groups, and high regioselectivity. Leveraging this method, we have successfully synthesized a diverse range of high-value carbazoles directly from N₂, including biologically active natural alkaloids (such as the anti-HIV drug Glycoborine and the antiviral compound Clausine V), optoelectronic materials (e.g., 11,12-dihydroindolo[2,3-a]carbazole), and ¹⁵N-labeled carbazoles. This approach not only expands the scope of carbon sources suitable for nitrogen incorporation from N₂ but also paves potential pathways for the development of diverse catalytic systems, offering new opportunities for the efficient synthesis of nitrogen-containing heterocycles.

Keywords

N₂ functionalization / Nitrogenation / Amination / C–N bond / Pd-catalyzed reaction / Carbazoles / Nitrogen-containing heterocycles / One-pot/two-step protocol

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2026 SIOC, CAS, Shanghai, & WILEY-VCH GmbH