Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles

Abstract

Herein, we report the successful syntheses of scarcely represented indole-based heterocycles which have a structural connection with biologically active natural-like molecules. The selective oxidation of indoline nucleus to indole, hydrolysis of ester and carbamoyl residues followed by decarboxylation with concomitant aromatization of the pyridazine ring starting from tetrahydro-1H-pyridazino[3,4-b]indole derivatives lead to fused indole-pyridazine compounds. On the other hand, non-fused indole-pyrazol-5-one scaffolds are easily prepared by subjecting the same C2,C3-fused indoline tetrahydropyridazines to treatment with trifluoroacetic acid (TFA). These methods feature mild conditions, easy operation, high yields in most cases avoiding the chromatographic purification, and broad substrate scope. Interestingly, the formation of indole linked pyrazol-5-one system serves as a good example of the application of the umpolung strategy in the synthesis of C3-alkylated indoles.

Synthesis of Azacarbolines via PhIO2-Promoted Intramolecular Oxidative Cyclization of α-Indolylhydrazones

“…Notably, this approach has resulted in a convenient assemblage of two biologically important heterocycles such as indole and pyridazine frameworks. The fusion of these two privileged heterocycles in one molecule 15 may create rigid entities endowed with either enhanced (synergistic effect) or new biological activities, which may feature promising bioactivity for screening. Furthermore, compared with Xiao and Xu’s protocol, 10 this method offers the clear advantage of not requiring the use of transition metal catalysts and harsh reaction conditions.…”