Trifluoromethyl Selenoxides: Electrophilic Reagents for C–H Trifluoromethylselenolation of (Hetero)Arene

Abstract

The trifluoromethylselenyl group (CF3Se) has become an emerging fluorinated moiety in synthetic chemistry due to its high Hansch lipophilicity parameter and strong electron-withdrawing effect. The trifluoromethylselenolation is hampered by limited synthetic methods and related reagents. Herein, we designed and synthesized the new electrophilic trifluoromethylselenolation reagents, trifluoromethyl selenoxides, which are easy to prepare and easy-to-handle and are not moisture or air sensitive. The selenoxides are successfully applied to metal-free C–H trifluoromethylselenolation of a series of (hetero)­arenes.

Lewis Acid Promoted Vicinal Oxytrifluoromethylselenolation of Alkenes

“…Due to the higher nucleophilicity of the indole moiety, reaction at room temperature or −20 °C resulted in a low yield (not shown). The difference between 2v and 2an was consistent with our previous result that benzothiophene was not a good substrate for C–H trifluoromethylselenolation . Further, the method could be well adapted for gram-scale synthesis without detriment to the yield ( 3t ), demonstrating the application potential of this reaction system.…”

“…The difference between 2v and 2an was consistent with our previous result that benzothiophene was not a good substrate for C−H trifluoromethylselenolation. 12 Further, the method could be well adapted for gram-scale synthesis without detriment to the yield (3t), demonstrating the application potential of this reaction system. Then, we set out to investigate the generality of this reaction with respect to solvents, which worked as nucleophiles (Table 2).…”

“…At the outset, we investigated the reaction of trifluoromethyl selenoxide 1a and styrene 2a with 1.2 equiv of Tf 2 O as an activator (Table 1). 12 The reaction was conducted with i-PrOH as solvent, and a 71% yield of desired product 4a was obtained (entry 1). Nevertheless, when the reaction was ran with EtOH, 3a was obtained in 94% yield (entry 2).…”

“…Consequently, compared with well developed difunctional trifluoromethylthiolation of alkenes, the development of difunctional trifluoromethyl­selenolation of alkenes with diverse nucleophiles is still in great demand. Recently, we have developed a new type of trifluoromethyl­selenolation reagents, trifluoromethyl selenoxides, which were successfully applied to metal-free C–H trifluoromethyl­selenolation of a series of (hetero)­arenes. , In continuation of our interest in the development of trifluoromethylselenolation reagents , and the synthesis of fluoro-containing compounds, herein, we present a metal-free three-component 1,2-oxytrifluoromethyl­selenolation and 1,2-aminotrifluoromethyl­selenolation of various alkenes (Scheme , 2).…”

Synthetic application of chalcogenonium salts: beyond sulfonium

“…Very recently, Yuan and co-authors have disclosed their findings on the trifluoromethylselenolation of arene and heteroarene substrates (Scheme 15). 30 Moisture and air-stable trifluoromethyl selenoxides 34 , which are easy to prepare and handle (they are crystalline reagents) were conveniently converted to selenonium salts 35 in an interrupted-Pummerer-like reaction. The treatment of 35 with i-propanol led to the formation of the desired products 36 and ether.…”