Gentle Route To Diazos

Diazo compounds are versatile intermediates in organic synthesis, but they are typically difficult to generate. Chemistry professor Ronald T. Raines and postdoctoral associate Eddie L. Myers of the University of Wisconsin, Madison, report a gentle high-yield method to generate diazo compounds, R=N₂, from azides, RN₃ (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200804689). The key to the reaction is an ester-containing phosphine reagent that reacts with azides to form phosphazides. An intramolecular acylation traps the phosphazide, which forms an acyl triazene upon hydrolysis. In the presence of a weak base, such as sodium bicarbonate, the acyl triazene fragments into a diazo compound and a primary amide. The researchers manage to bypass the Staudinger reaction, which uses similar starting materials to make amines, by using a strong acylating group. "Having a phosphine with a highly active acylating group allows us to do this chemistry," Raines says. The reaction works well for α-azido amides and esters but not as well for α-azido ketones because they fragment and form acyl hydrazones. Raines and Myers are currently developing water-soluble phosphine reagents to extend the methodology to chemical biology applications.