Science 335, 1471–1474 (2012)

Diazomethane (CH2N2) is widely used in organic synthesis, for example as a reagent in esterification, dipolar cycloaddition and epoxidation. However, the use of diazomethane is limited by its toxicity and explosiveness, and even its precursors are unsafe.

Now, Bill Morandi and Erick Carreira from the Laboratory of Organic Chemistry in Zürich have developed a reaction in which diazomethane is formed in situ and then consumed by a metal catalyst, which avoids significant build-up of it, removing the potential hazard. A catalyst for this reaction has to be made compatible with the strongly oxidizing and strongly alkaline aqueous conditions in which the diazomethane is formed. The team tested catalysts formed by a range of transition metals and the highest yields were obtained with an iron porphyrin, which is non-toxic and inexpensive.

In Morandi and Carreira's method, diazomethane is generated in the aqueous phase and migrates to the organic phase, where it reacts with the catalyst. Separating the catalyst from the harsh conditions required to generate diazomethane means it resists decomposition. The researchers achieved up to 89% yield for the cyclopropanation of a range of alkenes using the iron porphyrin catalyst. A water-soluble rhodium catalyst gave no product, but a hydrophobic one resulted in 45% yield, demonstrating the importance of the catalyst being compatible with the organic phase.