Mechanochemical synthesis of tetramic acids and their biomimetic ring expansion to 4-hydroxy-2-pyridones

Abstract

Mechanochemistry has emerged as a powerful tool for enabling solvent-free, energy-efficient, and sustainable chemical transformations. Herein, we report a concise mechanochemical strategy for the synthesis of 3-acyl-tetramic acids and their subsequent biomimetic ring expansion to 5-arylated-4-hydroxy-2-pyridones—privileged heterocycles with broad biological and synthetic relevance. Inspired by biosynthetic pathways, our approach utilizes iodine-mediated activation of the 5-arylidene moiety on tetramic acids to initiate a ring expansion under mild conditions.