Synthesis of benzo[a]carbazoles and indolo[2,3-a]carbazoles using a combined directed ortho metalation-cross coupling strategy

Benzo[a]- and indolo[2,3-a]carbazoles have demonstrated wide applications in both material science and pharmaceutical industry. The Directed ortho Metalation (DoM) - cross coupling strategy has been successfully used for synthesis of the benzo[a]- and indolo[2,3-a]carbazoles.; The benzo[a]- and hexyl[a]carbazoles were prepared from indole in 5 steps in overall yields of 40-55%. Using the same method, an unnamed indolo[2,3-a]carbazole alkaloid, as well as its N,N-dimethyl derivative, have been synthesized with overall yields of 42% and 4.8% in 8 steps from indole, respectively. In addition, structural studies of gramine methiodides reveal stereoelectronic effect in the N-MOM gramine methiodide for the first time. A biogenetic approach for the synthesis of calothrixin B, a metabolite of the unnamed indolo[2,3-a]carbazole alkaloid, was also explored.