One-Pot Synthesis of Novel Multisubstituted 1-Alkoxyindoles

Studies on a one-pot synthesis of novel multisubstituted 1-alkoxyindoles 1 and their mechanistic investigations are presented. The synthesis of 1 was successfully achieved through consecutive four step reactions from substrates 2. The substrates 2, prepared through a two-step synthetic sequence, underwent three consecutive reactions of nitro reduction, intramolecular condensation, and nucleophilic 1,5-addition to provide the intermediates, 1-hydroxyindoles 8, which then were alkylated in situ with alkyl halide to afford the novel target products 1. We optimized the reaction conditions for 1 focusing on the alkylation step, along with the consideration of formation of intermediates 8. The optimized condition was SnCl2 center dot 2H(2)O (3.3 eq) and alcohols ((ROH)-O-1, 2.0 eq) for 1-2 h at 40 degrees C and then, base (10 eq) and alkyl halides ((RY)-Y-2, 2.0 eq) for 1-4 h at 25-50 degrees C. Notably, all four step reactions were performed in one-pot to give 1 in good to modest yields. Furthermore, the mechanistic aspects were also discussed regarding the reaction pathways and the formation of side products. The significance lies in development of efficient one-pot reactions and in generation of new 1-alkoxyindoles.

Automated summary

This study presented the one-pot synthesis of novel multisubstituted 1-alkoxyindoles 1 and their mechanistic investigations. The optimized conditions for the reaction were discussed, focusing on the alkylation step and the formation of intermediates. The significance lies in the development of efficient one-pot reactions and the generation of new 1-alkoxyindoles.