# Oxetanes: formation, reactivity and total syntheses of natural products

## TL;DR

This paper reviews the synthesis, reactivity, and use of oxetanes in creating natural products, focusing on recent developments since 2015.

## Contribution

The paper provides an updated and comprehensive review of oxetane chemistry, including new synthetic methods and applications.

## Key findings

- Various synthetic strategies for oxetane formation are reviewed, including de novo ring constructions.
- Oxetanes show useful reactivity in ring-opening and ring-expansion reactions for natural product synthesis.
- Recent total syntheses of oxetane-containing natural products are highlighted.

## Abstract

Oxetanes are 4-membered cyclic monoethers which have found important applications in medicinal chemistry as polar and metabolically stable isosteric replacements for gem-dimethyl and carbonyl groups. This work reviews possible synthetic strategies towards these strained heterocycles, covering both de novo constructions of the 4-membered ring as well as derivatisations of oxetane building blocks, then reactivity of oxetanes in terms of ring-opening and ring-expansion reactions, and finally total syntheses of selected oxetane-containing natural products. The literature review primarily covers reports made after the year 2015, but a few older contributions that were considered relevant are also discussed.