Benzannulation of Pyrroles to 4,5‐Disubstituted Indoles through Brønsted‐Acid‐Promoted Rearrangement of tert‐Butyl Peroxides

Abstract

Benzannulation of pyrrole to indole was achieved by using γ‐carbonyl tert‐butyl peroxides as C4 building blocks. The reaction is initiated by Brønsted‐acid‐promoted rearrangement of the tert‐butyl peroxide, followed by annulation with pyrrole leading to an indole skeleton bearing 4,5‐disubstitutents. The salient features of this benzannulation approach include using readily available starting materials and mild reaction conditions.

Annulative π-Extension (APEX) of Indoles to Pyrido[1,2-a]indoles Using 4-Oxo Peroxides as C4 Units

“…However, this protocol failed to gain popularity due to the low selectivity and efficiency. Recently, we have reported that 4-oxo tert -butyl peroxides acted as versatile C4 building blocks for the selective synthesis of furans, pyrroles, as well as indoles via Brønsted acid-catalyzed Hock rearrangement of the peroxy group . Continuing with our interest in the manipulations of organoperoxides, we envisioned that APEX reactions of 3-substituted indoles with 4-oxo peroxides may enable the synthesis of analogous π-extended pyrido­[1,2- a ]­indoles in one step.…”

“…On the basis of the above experiment and literature reports, − a tentative mechanism was proposed (Scheme ). Initially, the protonation of the peroxide 2 gives the intermediate A , which undergoes the Hock rearrangement (1,2-migration of the phenyl group) to generate the key oxonium intermediate B .…”

Synthesis of functionalized indoles via cascade benzannulation strategies: a decade's overview

“…In 2017, Li and co-workers reported a Brønsted-acid-mediated annulative cyclization by employing 174 as a C4 building block for the construction of 4,5-disubstituted indole derivatives (Scheme 26). 35 Here, under the acidic conditions, peroxide 174 was first protonated and the 1,2-migration of the phenyl ring was initiated to generate oxonium intermediate 176 . After that, the reaction of pyrrole 175 with bis-electrophile 176 furnished intermediate 177 , which underwent a second intramolecular nucleophilic addition and subsequent aromatization by elimination of phenol and water to deliver the desired indoles 179 .…”

Recent Advances in Functionalization of Pyrroles and their Translational Potential

“…The mechanistic study reveals that tert‐butyl peroxide undergoes rearrangement which was commensed by Bronsted‐acid followed by annulations with pyrrole bringing about an indole framework incorporating 4,5‐ disubstitutents [165] …”