Expanding the Diversity of Azepino [3,2,1-hi] Indoles via Transition Metal-based Strategies such as Cross-coupling Reaction and Ring Closing Metathesis

Here we report several useful synthetic strategies to azepino hi-indoles, that are structural units in natural products by using commercially available indole derivatives such as 7-bromo indole and 7-formylindole via palladium catalyzed cross-coupling reaction, ring closing olefin metathesis (RCM) as key steps. Later, we extended this strategy to seven-membered fused indoles containing dioxano and dioxocano derivatives via allylation, double bond isomerization and RCM sequence as key step. Additionally, azepino indole having diene moiety was obtained by enyne metathesis and shown to be useful for Diels-Alder strategy. Along similar lines, we also report eight-membered fused azocino indole using Grignard reaction and RCM as key steps and we demonstrated that the product obtained is useful for Fischer indolization to obtain bis-indole derivative. Here several synthetically useful transformations were performed to generate diversity in the fused indole derivatives. All the compounds synthesized here are well characterized by NMR and HRMS data.Introduction

Automated summary

In this study, several synthetic strategies for azepino hi-indoles were reported. Commercially available indole derivatives such as 7-bromo indole and 7-formylindole were used as starting materials, and palladium catalyzed cross-coupling reaction and ring closing olefin metathesis (RCM) were employed as key steps. The strategy was also extended to seven-membered fused indoles and eight-membered fused azocino indoles. Various synthetically useful transformations were performed to generate diversity in the fused indole derivatives. The synthesized compounds were well characterized by NMR and HRMS data.