Application of Metal‐Free Dearomatization Reaction as a Sustainable Strategy to Direct Access Complex Cyclic Compounds

Abstract

The highly efficient construction of complicated heterocyclic frameworks in an atom‐ and step‐economic manner is still one of the cores of synthetic chemistry. Dearomatization reactions show the unique advantage for the construction of functionalized heterocycles and have attracted widespread attention over the past two decades. The metal‐free approach has proved to be a green and sustainable paradigm for the synthesis of spirocyclic, polycyclic and heterocyclic scaffolds, which are widely present in natural products and bioactive molecules. In this review, the advances in the recent six years (2017–2023) in metal‐free dearomatization reactions are highlighted. Emphasis is placed on developments in the field of organo‐catalyzed dearomatization reactions, oxidative dearomatization reactions, Brønsted acid‐ or base‐promoted dearomatization reactions, photoredox‐catalyzed dearomatization reactions, and electrochemical oxidation dearomatization reactions.

Synthesis of Pyrroloindolines via N-Heterocyclic Carbene Catalyzed Dearomative Amidoacylation of Indole Derivatives

“…The pyrroloindoline core structure can be found in numerous natural products, , such as roquefortine C, gliocladin C, and physostigmine (Scheme A), which are associated with biologically active molecules displaying antibacterial, anticancer, and cholinesterase inhibitory properties. − Given their promising activities, pyrroloindoline and its analogues have become attractive synthetic targets, garnering significant attention from the synthetic chemistry community. , Recent advances in photoredox catalysis have provided a robust method to construct N -containing heterocycles by manipulating amidyl radicals under mild conditions. , Taking advantage of radical dearomatization, , the Wang , and Xia groups independently reported amidyl radical cyclization reactions of indole derivatives for constructing the pyrroloindoline scaffold (Scheme B). The resulting C3a radical A could subsequently react with conventional radical acceptors, such as O 2 , acrylates, alkynyl sulfones, and TEMPO, yielding hydroxyl-, alkyl-, alkynyl-, and alkoxyamine-substituted pyrroloindolines, respectively.…”

Organocatalytic Dearomatization of 5-Aminopyrazoles: Synthesis of 4-Hydroxypyrazolines

“…Consequently, these motifs are increasingly used in drug synthesis, garnering the attention of synthetic organic chemists . Various dearomatization methods have emerged, using transition metals and metal-free conditions . Recently, light-induced dearomatization has proven to be effective in synthesizing saturated heterocycles. , These strategies convert π-excessive and π-deficient heterocycles into diverse saturated N,S,O-heterocycles, including indole, pyrrole, thiophene, furan, benzofuran, pyridine, quinoline, isoquinoline, quinoxaline, and others .…”