Web Date: December 13, 2016
Fluorinated azides click to make triazoles
With the help of new fluorinating reagents, a team led by Zsófia E. Blastik and Petr Beier of the Czech Academy of Sciences has devised a versatile fluorinated version of copper-catalyzed click chemistry. The approach overcomes some previous difficulties with preparing suitable fluorinated reagents for click reactions and opens the door to broader use of click chemistry, which has become invaluable to biochemistry and polymer science researchers.
The new chemistry hinges on the ability to make azidoperfluoroalkanes. Azidotrifluoromethane (CF3N3) has been known for some time, but its best reported synthesis starting from CF3I requires cumbersome handling of toxic and corrosive CF3NO, N2H4, and Cl2 gases—an approach that has limited CF3N3’s applications. Beier’s group alternatively attempted using electrophilic CF3I with sodium azide (NaN3) as a nucleophile, but the reaction didn’t work. Instead, the team found that CF3N3 and its previously unknown longer chain analogs can be prepared more conveniently from CF3Si(CH3)3 and related nucleophiles and sulfonyl azide electrophiles. In effect, the researchers flipped the polarity of the reaction’s constituents (Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201609715).
The reported azidoperfluoroalkanes undergo copper-catalyzed azide-alkyne cycloadditions, also known as click reactions, leading to N-perfluoroalkyl triazoles as underexplored building blocks, Beier says. “In fact, azidoperfluoroalkanes are more reactive in the click reaction with alkynes than nonfluorinated alkyl azides.”
“A reminder emerging out of this paper by Beier and colleagues is that, if you want to build a bond by a polar mechanism, there are always two options,” says Andrei K. Yudin of the University of Toronto, who focuses on the chemistry of heterocyclic compounds. “It is a good idea to reverse the polarity of components if one path is problematic. As a result, they have developed an efficient entry into azidoperfluoroalkanes.”
“This is a very attractive, scalable, one-step method for preparing azidotrifluoroalkanes,” adds Qilong Shen of the Shanghai Institute of Organic Chemistry, whose group develops new fluorinating reagents. The azides display excellent reactivity in click reactions, Shen says, “paving the way for the broad application of azidoperfluoroalkanes in many fields, including but not limited to chemical biology and materials science.”
CORRECTION: On Jan. 9, 2017, this story was updated to correct one of the starting reagents in the reaction scheme. It should be C8F17Si(CH3)3 rather than C8H17Si(CH3)3 as originally stated.
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