DMEAD: a new dialkyl azodicarboxylate for the Mitsunobu reaction

Di-2-methoxyethyl azodicarboxylate (DMEAD) is prepared in 65% yield in two steps as a crystalline solid. Use of DMEAD in the Mitsunobu reaction of a variety of alcohols with pronucleophiles results in good yields of the products under sufficient stereospecificity of inversion, as conventional diisopropyl azodicarboxylate (DIAD) does. Isolation of the product is, however, much easier with DMEAD than that with DIAD, because the hydrazine produced from DMEAD is highly hydrophilic and is completely separable by a simple extraction into neutral water. Purification of the organic layer, after separation of the other by-product, triphenylphosphane oxide, by filtration, easily provides high purity of the product in a good yield. Concentration of the water layer yields the hydrazine, which can be reused for the preparation of DMEAD. One-step removal of the two by-products by the aqueous extraction was also possible when trimethylphosphane and DMEAD were employed.