Piezocatalyzed cascade cyclization of 1,7-enynes with α-keto acids under ball milling

Abstract

Fused pyran motifs are key structural components in many bioactive compounds and pharmaceutical drugs. Traditional methods for synthesizing these heterocycles, such as Fe-catalyzed annulation and photocatalytic approaches, often face challenges including the use of precious metals, long reaction times, and reliance on solvents. Here, we introduce a mechanochemical, piezoelectric-catalyzed decarboxylative cascade cyclization of 1,7-enynes with α-keto acids using BaTiO₃ as a catalyst under ball-milling conditions. This method provides several advantages, including solvent-free conditions, significantly reduced reaction times (12 minutes), and no need for transition-metal catalysts or external photosensitizers. Additionally, the piezocatalyst demonstrates recyclability over multiple cycles with minimal loss in yield. Our approach offers a sustainable and efficient alternative to traditional catalytic systems, providing a versatile strategy for the synthesis of fused pyran derivatives.