Diazoalkane Expands Fluorine Focus On Ethyl Groups

Developing new methods for introducing fluorine into complex organic molecules has been all the rage during the past few years. Researchers preparing drug candidates and crop protection chemicals typically seek to add a single fluorine atom or trifluoromethyl group and now have myriad ways to do so. But methods for adding longer, more lipophilic perfluoroalkyl groups such as penta­fluoroethyl, –C₂F₅, to complex molecules are relatively scarce. The approaches tend to be direct additions of perfluoroalkyl groups using organometallic transfer reagents and don’t use perfluoroalkyl-containing building blocks. Pavel K. Mykhailiuk of Enamine, a global supplier of research chemicals based in Kiev, Ukraine, has now developed a new building block for introducing C₂F₅ into organic molecules (Chem. Eur. J. 2014, DOI: 10.1002/chem.201304840). Mykhailiuk safely generates the fluorinated diazoalkane, C₂F₅CH=N₂, in situ from C₂F₅CH₂NH₂•HCl and NaNO₂. He demonstrated the utility of the reagent by using it in [3 + 2] cycloadditions with alkenes to prepare perfluoroethylated pyrazolines (one example shown) with better than 95% conversion rates. Mykhailiuk believes the diazofluoroalkane will also be as useful as other diazoalkanes for cyclopropanations, carbene insertions, and alkyne cycloadditions.