Mechanochemistry Enables Rapid and Solvent-Free Wittig Reactions on Sugars

The development of efficient olefination methods for carbohydrates is of strategic relevance, as sugars are chiral and naturally abundant. They serve as valuable scaffolds in drug discovery and asymmetric synthesis. Herein, we report a mechanochemical approach for the Wittig olefination of various sugar substrates, enabling fast and solvent-free olefin formation under ambient conditions. The protocol proceeds with high functional group tolerance, accommodating both acetonide- and benzyl-protected aldoses as well as unprotected sugars, giving access to a variety of structurally diverse olefins. Kinetic studies revealed that the reaction reaches significant conversion within minutes of milling, despite the inherently low availability of the free aldehyde in mutarotational equilibrium. A comparative evaluation against a conventional solution-based protocol demonstrated clear advantages of the mechanochemical approach in terms of operational simplicity and waste reduction.