Mykhailiuk, P. K. Generation of C2F5CHN2 In Situ and Its First Reaction: [3+2] Cycloaddition with Alkenes Chem. Eur. J. 2014, 17, 5168. (Back Cover Picture)
Ritter, S. K. Diazoalkane Expands Fluorine Focus On Ethyl Groups Chemical & Engineering News, 92 (17), 2014.
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 C2F5 using organometallic transfer reagents and don’t utilize C2F5-containing building blocks.
Enamine scientists have developed a new building block for introducing C2F5 group into organic molecules. Pavel Mykhailiuk and colleagues safely generated the fluorinated diazoalkane, C2F5CHN2, in situ from C2F5CH2NH2•HCl and NaNO2. Authors demonstrated the utility of the reagent by using it in [3 + 2]-cycloadditions with mono- and disubstituted alkenes at room temperature to prepare perfluoroethylated pyrazolines with better than 95% conversion rates. Authors believe the diazofluoroalkane will also be as useful as other diazoalkanes for cyclopropanations, carbene insertions, and alkyne cycloadditions.