Design of Trifluoroalkenyl Iodonium Salts for a Hypervalency‐Aided Alkenylation–Cyclization Strategy: Metal‐Free Construction of Aziridine Rings

• Published in: Angewandte Chemie International Edition 2018-05, Vol.57 (22), p.6643-6647
• Main Authors: Mészáros, Ádám, Székely, Anna, Stirling, András, Novák, Zoltán
• Format: Article
• Language: English
• Subjects: Amines; aziridines; Catalysts; Chemical synthesis; Construction; cyclization; Fluorination; heterocycles; Heterocyclic compounds; iodonium salts; Metals; Reagents; Salts; trifluoromethyl substituents
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201802347

The synthesis of fluorinated compounds and their use as pharmaceutical ingredients or synthetic building blocks have been in the focus of chemical and medicinal research. However, the efficient synthesis of trifluoromethylated nitrogen heterocycles is sometimes challenging. Herein, we disclose a simple aziridination process that relies on the use of amines and novel alkenyl iodonium reagents for the synthesis of strained, trifluoromethylated heterocycles. With the utilization of a newly designed and bench‐stable but highly reactive hypervalent alkenyl iodonium species, these three‐membered‐ring heterocyclic compounds can be efficiently constructed from simple amines under mild conditions in the absence of transition‐metal catalysts. The special reactivity of the new trifluoropropenyl synthon towards nucleophilic centers could be exploited in more general cyclization and alkenylation reactions in the future. A bench‐stable but highly reactive hypervalent trifluoromethylalkenyl iodonium species was designed as an electrophilic reagent for the functionalization of nucleophilic species such as primary amines. An alkynylation–cyclization strategy enables the efficient transition‐metal‐free construction of aziridine rings under mild reaction conditions.