Recent Advances and Uses of (Me₄N)XCF₃ (X=S, Se) in the Synthesis of Trifluoromethylthiolated and Trifluoromethylselenolated Compounds

Abstract

The introduction of trifluoromethylthio (SCF 3) and trifluoromethylseleno (SeCF 3) substituents into organic molecules significantly improves the electron-withdrawing and lipophilic properties of their parent compounds. Therefore, a vast class of versatile reagents were employed to access the corresponding fluorine-containing compounds. Among them, tetramethylammonium salts, such as (Me 4 N)SCF 3 and (Me 4 N) SeCF 3 , have been employed as practical and efficient non-metal reagents for developing efficient trifluoromethylthiolation and trifluoromethylselenolation in recent years. This Minireview systematically illustrates the application of (Me 4 N)XCF 3 (X=S, Se) in the synthesis of trifluoromethylthiolated and trifluoromethylselenolated compounds, and its content is divided into two categories: transition-metalcatalyzed reactions, and transition-metal-free reactions. Scheme 13. Metal-free trifluoromethylthiolation and trifluoromethylselenolation of alkynyl(phenyl) iodoniums with (Me 4 N)SCF 3 and (Me 4 N) SeCF 3. [45] Scheme 14. Metal-free trifluoromethylthiolation of arenediazonium salts with (Me 4 N)SCF 3. [46] Scheme 15. Catalyst-and additive-free trifluoromethylselenolation of organic halides, diaryliodonium triflate, aryldiazonium tetrafluoroborates and αdiazo carbonyls with (Me 4 N)SeCF 3. [49] Scheme 16. Metal-free trifluoromethylthiolation of cyclic sulfamidates with (Me 4 N)SCF 3. [50] Minireview 69

Recent trends in dehydroxylative trifluoro-methylation, -methoxylation, -methylthiolation, and -methylselenylation of alcohols

“…Compared to trifluoromethylation, trifluoromethoxylation, and trifluoromethylthiolation, the direct trifluoromethylselenylation of alcohols is relatively less explored, although there has been much recent attention on the development of novel and efficient methodologies for the synthesis of SeCF 3 -substituted compounds. 34 In 2019, in the same study describing the deoxytrifluoromethylthiolation of alcohols with the benzothiazolium salt BT-SCF 3 , Hopkinson's research team reported the successful NEt( i Pr) 2 -promoted preparation of trifluoromethylselenoalkanes 36 from the respective alcohols 34 employing 2-trifluoromethylseleno-substituted benzothiazolium salt (BT-SeCF 3 ; 35) ( Scheme 20 ). 31 Notably, BT-SeCF 3 was synthesized via the same general strategy used to prepare BT-SCF 3 .…”

Gold (I/III)‐Catalyzed Trifluoromethylthiolation and Trifluoromethylselenolation of Organohalides

“…The unique Hansch parameters of CF 3 S and CF 3 Se provide the medicinal chemist with a convenient tool for adjusting the lipophilicity of bioactive molecules, whereas their electron‐withdrawing properties and considerable steric hindrance enhance the metabolic stability of the molecules containing these fluorinated groups. Not surprisingly, synthetic methodologies that introduce SCF 3 and SeCF 3 are being actively pursued [1b,c, 4] . Among them, the direct trifluoromethylthiolation and trifluoromethylselenolation of organohalides with palladium, [5] nickel, [6] and copper [7] have gained the most traction [8] (Scheme 1A).…”

Electrochemical Trifluoromethylselenolation of Activated Alkyl Halides

“…[21,22,36] Conversely, access to alkyl trifluoromethylselenylated entities has proven more challenging, and to date, only a few strategies have been described in the literature. [21][22][23]37] The most expedient way to afford such compounds remains the direct nucleophilic substitution of activated alkyl species with the CF 3 Se À anion to forge the desired C(sp 3 )À SeCF 3 bond (Scheme 1B). [21][22][23]37] Due to the synthetic challenge associated to the generation of the CF 3 Se À anion, several copper-based methodologies have been reported (Scheme 1B, a).…”

“…[21][22][23]37] The most expedient way to afford such compounds remains the direct nucleophilic substitution of activated alkyl species with the CF 3 Se À anion to forge the desired C(sp 3 )À SeCF 3 bond (Scheme 1B). [21][22][23]37] Due to the synthetic challenge associated to the generation of the CF 3 Se À anion, several copper-based methodologies have been reported (Scheme 1B, a). [38][39][40] In 2003, Tyrra and co-workers reported the convenient synthesis of the air-stable (Me 4 N)SeCF 3 reagent [41] which was subsequently used as a trifluoromethyselenylating reagent with various electrophiles by the Zhang group (Scheme 1B, b).…”

“…The direct formation of C(sp 2 )−SeCF 3 bond formation has been extensively studied and elegant trifluoromethylselenolation methods for the functionalization of aryl compounds have been reported [21,22,36] . Conversely, access to alkyl trifluoromethylselenylated entities has proven more challenging, and to date, only a few strategies have been described in the literature [21–23,37] . The most expedient way to afford such compounds remains the direct nucleophilic substitution of activated alkyl species with the CF 3 Se − anion to forge the desired C(sp 3 )−SeCF 3 bond (Scheme 1B) [21–23,37] .…”