Recent Advances in the Development of Direct Trifluoromethylselenolation Reagents and Methods

Abstract

The introduction of trifluoromethylchalcogen group (CF 3 O, CF 3 S and CF 3 Se) has attracted growing attention in the field of modern organofluorine chemistry. Compared with the CF 3 S and CF 3 O chemistry, methods for trifluoromethylselenolation are much less developed owing to the limited availability of CF 3 Se transfer reagents and synthetic methods. The CF 3 Se group introduces promising lipophilicity (Hansch-Leo parameter = 1.29) and strong electron-withdrawing effect (Hammett constants σ m = 0.44, σ p = 0.45) which are important parameters for the development of new pharmaceutically relevant compounds. Traditionally, the CF 3 Se compounds were synthesized by the nucleophilic trifluoromethylation of diselenides and selenocyanates, which suffered from harsh conditions and/or limited substrates scope. Compared with the indirect methods, the direct formation of CÀ SeCF 3 constitutes is a more efficient approach. In recent years, new reagents and methods were developed which enabled the incorporation of the trifluoromethylselenyl group directly under mild conditions, specifically in transition metal catalysis and photoredox catalysis. In this review, we will focus on direct trifluoromethylselenolation strategies based on the development of new trifluoromethylselenolation reagents and methods. 2.1. MÀ SeCF 3 (M=Hg, Cu, Ag) 2.2. [(bpy)CuSeCF 3 ] 2 2.3. (Me 4 N)SeCF 3 2.4. BTÀ SeCF 3 3. Electrophilic Trifluoromethylselenolation Reagents 3.1. In situ formed CF 3 SeCl from BnSeCF 3 + SO 2 Cl 2 3.2. TsSeCF 3 4. Miscellaneous 5. Conclusions

Electrochemical Trifluoromethylselenolation of Activated Alkyl Halides

“…If to date, the trifluoromethyl (CF 3 ) is the most used fluoroalkyl group, trifluoromethyl chalcogens (OCF 3 , SCF 3 and SeCF 3 ) are of significant interest since their increased lipophilicity and steric hindrance can considerably alter the properties of organic molecules [20,21] . Out of the three trifluoromethyl chalcogens, SeCF 3 has received less attention [21,22] as some Se‐containing substrates are sensitive to air and present high toxicity [23] . However, selenium is a crucial trace element of the human machinery, [24–26] and selenolated compounds have found plethora of applications in multiple areas including life sciences and materials [27–33] .…”

“…[27][28][29][30][31][32][33] Therefore, several research groups recognized the potential of merging the CF 3 group with selenium, especially in the context of drug design, [34,35] to incorporate SeCF 3 moieties into organic structures. [21][22] The direct formation of C-(sp 2 )À 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.…”

“…[21,22,36] 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).…”

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

“… 3 However, there are no analogous CF 3 Se-containing drugs, which is likely due to the limited synthetic options for their preparation. 4 Compounds containing the titled functionalities are versatile synthetic intermediates and can function as suitable building blocks for the preparation of many valuable functional materials. 5 Considering the widespread biological activities and synthetic usefulness of CF 3 /OCF 3 /SCF 3 /SeCF 3 -containing compounds, it has been of great synthetic interest to develop new, efficient, and practical methods for the introduction of these privileged moieties into organic molecules.…”