The preparation of C-5 alkylation products of indolines and indoles via a new approach

Indole and indoline frameworks represent one of the most important structural subunits of many natural and synthetic compounds. In this work, the synthesis of C-5 alkylation products of indoline and indole derivatives was aimed. Nitrogen atom of indoline was protected by benzyl group and the electrophile molecule was directed to benzene ring of indoline. Lewis acid-catalyzed reaction of β-nitrostyrene and N-benzyl indoline was selected as an example reaction and optimization studies were carried out. In the determined optium reaction conditions, C-5 alkylated indolines were obtained via Zn(OTf)2-catalyzed Michael type Friedel-Crafts reaction using various nitroalkenes. C-5 alkylated indole derivatives were also synthesized via oxidation of these alkylated indolines. Studies on the deprotection of the benzyl group in both indoline and indole derivatives were performed. Also, benzyl-free indolines were oxidized to the corresponding indoles. The nitro groups of molecules to the amine groups were reduced, thus the amine intermediates for the synthesis of novel analogues of silodosin which was used as medicines in the treatment of benign prostate hypertrophy were obtained. Characterization of the products was done by NMR and IR spectroscopies, high-resolution mass and elemental analysis.