Sustainable Transition Metal Free Synthesis of Substituted γ-Lactones

A novel and efficient methodology has been established for the synthesis of substituted γ-lactone scaffolds using a metal-free iodine/DMSO system. This approach offers a straightforward, practical, and environmentally benign alternative to conventional methods, delivering γ-lactones in good to excellent yields. The reaction employs molecular iodine as a catalyst and dimethyl sulfoxide (DMSO) as the solvent—both of which are inexpensive, commercially available, and non-toxic. Notably, this method eliminates the need for transition metals or complex catalytic systems, making it a cost-effective and sustainable route for lactone synthesis. In the broader context of green and sustainable chemistry, the development of methodologies that minimize environmental impact while maximizing efficiency remains a key objective. This protocol addresses those goals by utilizing simple, readily available starting materials and operating under mild reaction conditions, ensuring tolerance for various functional groups. The iodine/DMSO system reduces chemical waste and avoids hazardous reagents, aligning with the principles of atom economy and environmental safety. The use of iodine, a non-toxic halogen, further enhances the method’s appeal from a sustainability standpoint. Moreover, the operational simplicity and scalability of this process make it suitable for applications in both research and industrial settings. Given the importance of γ-lactone structures in pharmaceuticals, natural products, and fine chemicals, this methodology represents a valuable tool for synthetic chemists. Overall, the iodine/DMSO protocol offers a reliable, metal-free, and eco-friendly alternative for constructing γ-lactones, with strong potential for broader application and further development in modern organic synthesis.