Efficient construction of functionalized pyrroloindolines through cascade radical cyclization/intermolecular coupling

Chem Sci. 2024 Jan 4;15(6):2205-2210. doi: 10.1039/d3sc05210a. eCollection 2024 Feb 7.

Abstract

Pyrroloindolines are important structural units in nature and the pharmaceutical industry, however, most approaches to such structures involve transition-metal or photoredox catalysts. Herein, we describe the first tandem SET/radical cyclization/intermolecular coupling between 2-azaallyl anions and indole acetamides. This method enables the transition-metal-free synthesis of C3a-substituted pyrroloindolines under mild and convenient conditions. The synthetic utility of this transformation is demonstrated by the construction of an array of C3a-methylamine pyrroloindolines with good functional group tolerance and yields. Gram-scale sequential one-pot synthesis and hydrolysis reactions demonstrate the potential synthetic utility and scalability of this approach.