(Diazomethyl)dimethylphosphine Oxide - A Diazoalkane Reagent for [3+2] Cycloadditions

A safe and efficient method for the in-situ preparation of (diazomethyl)dimethylphosphine oxide - a hereto unexplored diazoalkane reagent - is developed. The method is based on the diazotization of the corresponding P(O)Me2-substituted amine (readily available in multigram quantities) in non-aqueous media. The protocol provides the target product as ca. 1.5 M CHCl3 solution which is stable at -18 degrees C. The utility of the synthesized diazoalkane is illustrated by its [3+2] cycloaddition with electron-poor alkynes and alkenes providing the corresponding P(O)Me2-substituted pyrazoles and pyrazolines with moderate to good efficiency. In this view, the title compound represents and an important extension of medicinally relevant phosphine oxide reagents. An efficient protocol for the generation of (diazomethyl)dimethylphosphine - a novel diazoalkane reagent - based on the diazotization reaction under anhydrous conditions is described. The title compound can be prepared as ca. 1.5 M solution in chloroform and can be stored at -18 degrees C for at least a month. The proposed reagent readily undergoes [3+2] cycloaddition with various electron-poor alkynes and alkenes providing the corresponding Me2P(O)-substituted pyrazoles and pyrazolines, respectively. image