Synthesis of Diethyl (1‐Diazo‐2‐oxopropyl)phosphonate

Abstract

Abstract This chapter presents the procedure for synthesis of Diethyl (1‐Diazo‐2‐oxopropyl)phosphonate. Diethyl and dimethyl (1‐diazo‐2‐oxopropyl)phosphonate are versatile building blocks for organic synthesis. These diazo compounds react via dipolar cycloaddition and other pathways to provide access to diverse classes of nitrogen heterocycles including phosphoryl substituted pyrazoles, triazolines, oxazoles, and thiazoles. Although commercially available, both diethyl and dimethyl (1‐diazo‐2‐oxopropyl)phosphonate are relatively expensive and so many labs opt to prepare the reagents which can then be stored indefinitely for use in the Ohira‐Bestmann homologation and other reactions. Several groups have reported the application of diazo transfer to dialkyl (2‐oxopropyl)phosphonate as an efficient method for the preparation of the “Ohira‐Bestmann reagents”. In addition, the sulfonamide byproduct formed in the reaction of the sulfonyl azide can be separated by filtration, simplifying the purification of the diazo product by chromatography.