Deoxytrifluoromethylthiolation and Selenylation of Alcohols by Using Benzothiazolium Reagents

Abstract

Aliphatic compounds substituted with medicinally importantt rifluoromethylthio (SCF 3 )a nd trifluoromethylselenyl (SeCF 3 )g roups weres ynthesized directly from alcohols by using the new benzothiazolium salts BT-SCF 3 and BT-SeCF 3 .T hese bench-stable fluorine-containing reagents are facile to use and can be prepared in two steps from non-fluorinated heteroaromatic startingm aterials. The metal-free deoxytrifluoromethylthiolation process using BT-SCF 3 proceeds under mild conditions and the similarly efficient trifluoromethylselenylationr eactions using BT-SeCF 3 are, to the besto fo ur knowledge, the first reported examples of this transformation.Scheme1.a) Benzothiazolium Reagents BT-SCF 3 and BT-SeCF 3 .b )Previously reported deoxytrifluoromethylthiolation reactionso fa liphatic alcohols. c) This work: Deoxytrifluoromethylthiolation and selenylation of alcohols with BT-SCF 3 and BT-SeCF 3 .[bmim] = 1-Butyl-3-methylimidazolium.[a] S.Scheme2.a) Two-step synthesisofBT-SCF 3 and its applicationi nthe deoxytrifluoromethylthiolation of aliphatic alcohol 2a.b)Likely reaction mechanism via 2-alkoxybenzothiazolium salt 4.

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

“…tion mixture by NMR revealed the formation of two products: the desired (pentafluoroethyl) thioether 3a in 78% NMR yield and a second species with 19 F and 1 H spectra consistent with the trifluoromethyl thionoester 4a (7% NMR yield, Table 1, entry 1). The formation of both species can be explained by the mechanism shown in Scheme 3 [36]. Nucleophilic attack of the alcohol in the presence of NEt(iPr) 2 at the C2-position of the BT reagent affords the key electrophilic 2-alkoxybenzothiazolium species A and the perfluoroalkylthiolate anion.…”

“…In 2019, we reported a new reagent for nucleophilic trifluoromethylthiolation based on the benzothiazolium motif: BT-SCF 3 [36][37][38]. This easily handled solid, which is stable at least over several months under ambient conditions, could be engaged in efficient deoxygenative trifluoromethylthiolation reactions of readily available aliphatic alcohols.…”

Insights into the Recent Synthetic Advances of Organoselenium Compounds

“…These trifluoromethylselenylated products come with a Hansch parameter (π) of 1.29 and Hammett constants σ m and σ p of 0.44 and 0.45, respectively, which imparts a peculiar lipophilic and electronic properties and favours their biological application. [168] Walsh et al, [169] pioneered selenenate anion as an active organocalatyst employed for the synthesis of trans-stilbenes 92 via dehydrohalogenation coupling of benzyl halides 91 with good to excellent yields. This approach was inspired by the dehydrohalogen coupling and cross coupling potential of sulfenate anions to give stilbenes and diaryl acetylenes respectively introduced by the authors.…”

Markovnikov-Type Hydrotrifluoromethylchalcogenation of Unactivated Terminal Alkenes with [Me4N][XCF3] (X = S, Se) and TfOH

“…To date, there have been two major strategies for the synthesis of SeCF 3 -substituted molecules: indirect and direct approaches [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. The indirect method comprises the trifluoromethylation of selenols, diselenides, and selenocyanates with diverse CF 3 transfer reagents, including CF 3 SO 2 Na/oxidant, TMSCF 3 /fluoride, HCF 3 /base, CF 3 I/TDAE (tetrakis(dimethylamino)ethylene), and so on.…”

“…However, these reactions suffer from harsh conditions, low efficiency, poor functional group tolerance, narrow substrate scope, and/or toxicity and pre-functionalization of starting materials, which limit their practical applications [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Notably, the direct trifluoromethylselenolation offers an elegant way to the C-SeCF 3 bond formation by using elaborate SeCF 3 reagents, such as CuSeCF 3 , Hg(SeCF 3 ) 2 , [(bpy)[Cu(SeCF 3 )] 2 , AgSeCF 3 , [Me 4 N][SeCF 3 ], ClSeCF 3 , and TsSeCF 3 [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Among these reagents, [Me 4 N][SeCF 3 ] is thermally stable, non-volatile, easy to handle, and readily accessible, and has become one of the most important SeCF 3 sources by far [ 48 ].…”