Catalyst-Free Synthesis of Phosphinochalcogenoic Anhydrides via Oxygen–Chalcogen Exchange with Elemental Sulfur or Selenium

Abstract

A novel catalyst-free, three-component strategy for the synthesis of phosphinothioic/phosphinoselenoic anhydrides has been developed, employing elemental sulfur or selenium, acyl chlorides (or anhydrides), and H-phosphine oxides. This protocol operates under mild conditions, exhibits a broad substrate scope with excellent functional group tolerance, including complex drug-like molecules such as ibuprofen derivatives, and is readily scalable. A comparative green metric analysis reveals a lower reagents-only E-factor compared to classical methods, underscoring its waste-minimizing profile. Notably, several synthesized compounds display preliminary antitumor activity against hepatoma cells (HepG2), highlighting the potential applicability of this methodology in medicinal chemistry and related fields.