Carbazole synthesis from 2-aminobiphenyl via intramolecular C-H activation and C-N bond formation

Carbazoles are a significant class of N-heterocyclic compound and an essential structural motif in several natural products and active pharmaceutical ingredients (APIs).[1] Therefore, considerable attention has been made to synthesize series of variously substituted carbazoles. Numbers of synthetic methods leading to the carbazole scaffold have been reported. The major problems of these synthetic methods are: 1) the need of protecting/auxiliary group to the and 2) requirement of long reaction time, and sometimes 3) the necessities of complex and expensive catalyst. In our work, we have developed a synthesis leading to the Carbazole scaffold, that starts with a C-C bond formation by means of tailored Suzuki cross-coupling protocol that involves chloroarene and phenylboronic acid to obtain the 2-nitrobiphenyl.[2] A new method for reduction of the aromatic nitro compounds into the corresponding aniline was elaborated.[3] The final synthetic step requested an intramolecular cyclisation to form the target N-heterocyclic scaffold. For this issue, we designed and developed an efficient tandem C-H activation and C-N bond formation process.[4] This method involved both the free amine and the arene moiety. The method showed up to tolerate a variety of functional groups on the two rings. The ring-closing protocol might showed-up to also operate with 2-N-acetaminobiphenyls to afford the corresponding 1-(9H-carbazol-9-yl)ethan-1-one. REFERENCES 1. H.-J. Knölker and K. R. Reddy, Chem. Rev. 2002, 102, 4303-4427. 2. V. Elumalai, A.H. Sandtrov, H.-R. Bjørsvik. Eur. J. Org. Chem. 2016, 1344-1354. 3. V. Elumalai, H.-R. Bjørsvik, Tetrahedron Lett. 2016, 57, 1224. 4. H.-R. Bjørsvik, V. Elumalai. Eur. J. Org. Chem. 2016, 5474-5479.