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

Abstract

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.

Vicinal difunctionalization of carbon–carbon double bond for the platform synthesis of trifluoroalkyl amines

“…Moreover, in alkenyliodonium salts 64 – 68 the carbon–carbon bond is activated to accept nucleophiles. A perfect candidate of this reagent class for the realization of our goals is trifluoroalkenyl-iodonium salt 1 as a stable potential synthon 69 allowing for the vicinal functionalization with two nucleophilic species. We expected that the secondary amine nucleophile would attach to the β -carbon due to the excellent Michael-acceptor character of the terminal sp 2 carbon center and form a stabilized iodonium ylide intermediate first.…”

Photocatalytic Palladium-Catalyzed Fluoroalkylation of Styrene Derivatives

“…In continuation of our studies in the field of fluoroalkylation reactions 3a , 3b , 10 and photocatalytic transformations, 11 we aimed to take advantage of the photo-Heck-type coupling approach to introduce more versatile fluoroalkyl groups into the styrene moiety using palladium catalysis and visible light irradiation ( Scheme 1 ). The classical palladium catalyzed cross-coupling reaction 12 involves a well-established two-electron redox mechanism typically between the Pd(0)/Pd(II) oxidation states.…”

Fluoroalkylations and Fluoroalkenylations with Iodonium Salts

“…Our research group synthesized a new fluoroalkenyliodonium salt ( 198 ) from the commercially available 3,3,3‐trifluoro‐2‐iodoprop‐1‐ene ( 192 ) using H 2 O 2 as oxidizing agent in TFA at 0 °C (Scheme 37). [59] In the second step, several aromatic compounds were used as nucleophile, and the desired fluoroalkenyliodonium species ( 195 – 198 ) were isolated in good yields, with the exception of mesityl derivative ( 194 ). This commonly used aromatic system, frequently used for diaryliodonium synthesis, did not worked, supposedly due to steric hindrance.…”

“…First, reaction between primer amines and the iodonium salt 198 was examined, and we observed the formation of trifluoromethyl aziridines ( 199 ) in case of aromatic, heteroaromatic and aliphatic derivatives. (Scheme 38A) [59] . The reaction proceeds without base to some extent (42 % yield), but the presence of Na 2 CO 3 improved the efficiency of the synthesis (82 % yield).…”