Mechanochemical one-pot synthesis of complex alkenes

Densely functionalized alkenes are often utilized as excellent tools for further functionalization of molecules. Recent progress in their synthesis includes nucleophilic addition to vinylbenziodoxolones (VBX) and vinylbenziodoxolones (VBO) to reach alkenes with complete regio- and stereocontrol. However, combining these two steps into a one-pot reaction would be challenging to develop in solution due to a mismatch in reaction solvents. In this work, we leverage the inherent properties of mechanochemistry to enable an efficient transition metal-free one-pot route to (bis)heteroatom-substituted (Z)-alkenes directly from ethynylbenziodoxol(on)es (EBX/EBO), avoiding the isolation of VBX/VBO. We demonstrate a high-yielding synthesis of a large variety of N/O/S-VBX reagents, which combined with the telescoped nucleophilic addition delivers a wide range of novel, complex (Z)-alkenes. The unique mechanochemical activation offered by solventless, solid-state mixing also enables formation of products whose synthesis is inefficient with solvent-based methods.