# Thiophene Derivatives as Versatile Precursors for (Hetero)Arene and Natural Product Synthesis

## TL;DR

This paper reviews how thiophene compounds can be used to build complex chemical structures important for drug and natural product synthesis.

## Contribution

The paper provides a concise overview of thiophene-based strategies for constructing functionalized (hetero)arenes and natural products.

## Key findings

- Thiophenes can form substituted benzenes via photocatalytic cycloaddition.
- Thiophene derivatives enable cascade reactions to build complex frameworks.
- Tetrahydrothiophenes allow cis-dialkylation of electron-poor olefins.

## Abstract

Thiophenes and their saturated analogues are versatile C4‐building blocks used to construct structurally intricate ring systems found in various biologically active structures. For instance, thiophenes can undergo dearomative cycloaddition reactions under photocatalytic conditions forming highly substituted benzenes. Thiophene S‐oxides and S,S‐dioxides have emerged as valuable precursors for the construction of complex frameworks in (4 + 2)/retro‐(4 + 1) cascade reactions through cheletropic release of SO or SO2, respectively. In addition, 2,5‐dihydrothiophenes can be rapidly converted into furans or pyrroles via pericyclic cascade reactions. The installation of a tetrahydrothiophene followed by reductive deletion of the sulfur atom has been demonstrated to be a powerful method for the cis‐dialkylation of electron‐poor olefins. The ability to generate highly complex, aromatic scaffolds and quaternary stereocenters makes thiophene compounds valuable intermediates for synthesizing natural products and bioactive molecules, which are important for crop science and medicinal chemistry. This minireview provides an overview of strategies for using these sulfur‐containing heterocyclic precursors in challenging synthetic applications.

Hidden but Powerful: Thiophenes and their saturated analogues have been demonstrated to be versatile C4‐building blocks that can be rapidly applied to natural product synthesis and the construction of functionalized (hetero)arenes. This minireview aims to provide a concise overview of the strategies and implementations of these sulfur‐containing heterocyclic precursors in challenging synthetic applications.