A unified protocol for the synthesis of chromones, thiochromones and γ-pyrones via a dehydrative rearrangement reaction at room temperature

Abstract

In this study, we present our discovery that a combination of dichloromethyl methyl ether (DCME) and a Lewis acid, a reaction condition traditionally used for Rieche formylation, is capable of activating 1,3-dioxin-4-ones and 1,3-oxathiin-6-ones chemoselectively at room temperature. This activation triggers an intriguing dehydrative rearrangement (DHR) reaction, yielding chromone, thiochromone and γ-pyrone derivatives with diverse substitutions. This protocol leverages widely available starting materials and feedstock reagents, offering a mild, practical, and scalable approach that delivers products in good to excellent yields with broad functional group compatibility. In addition, kinetic studies revealed that the DCME/Lewis acid conditions preferentially facilitate the DHR reaction over Rieche formylation on electron-neutral and moderately electron-rich aromatics. The widespread availability and operational simplicity of this method bode well for its broad and rapid adoption in various applications.