Preparation of 1‑Azido-2-Bromo-1,1,2,2-Tetrafluoroethane and Its Use in the Synthesis of N‑Fluoroalkylated Nitrogen Heterocycles

• Published in: Journal of organic chemistry Vol. 85; no. 17; pp. 11482 - 11489
• Main Authors: Tichý, David, Košt́ál, Vojtěch, Motornov, Vladimir, Klimánková, Iveta, Beier, Petr
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.09.2020; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; CHEMISTRY
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.0c01610

A straightforward synthesis of 1-azido-2-bromo-1,1,2,2-tetrafluoroethane on a multigram scale from 1,2-dibromotetrafluoroethane and sodium azide in a novel process initiated by organomagnesium compounds (i-PrMgCl·LiCl, turbo Grignard) is reported. Synthetic utility of the title azide in the preparation of N-tetrafluoroethylated and N-difluoromethylated five-membered nitrogen heterocycles was demonstrated with azide-alkyne cycloaddition to N-bromotetrafluoroethyl 1,2,3-triazoles, subsequent reduction to N-tetrafluoroethyl triazoles, rhodium-catalyzed transannulation with nitriles to N-tetrafluoroethylated imidazoles and rhodium-catalyzed ring-opening, and cyclization to N-difluoromethylated oxazoles and thiazoles.