Copper‐Mediated Halotrifluoromethylation of Unactivated Alkenes

Abstract

Ac opper-mediated halotrifluoromethylation of unactivated alkenesusing Umemotos reagent and copper(I) halide (CuX, X = Cl, Br, and I) was developed. TheC uX species (CuI, CuBr, and CuCl) were chosen as the source for bothc opper andh alides because of theirb enchtop stability,c ommercial availability,a nd relatively low cost. Simple exchange of the copper salt provided the desired simultaneous and regioselective incorporation of the halogen atom and of the CF 3 group to various alkenes. This protocol offers an efficienta nd practical route to various b-halotrifluoromethylateda lkanes.F urther modifications of the C À Br bond to C À B, C À Na nd C À Sb onds were performed. These derivatizations show the feasibility of late-stage modifications.

Recent Advances on the Halo- and Cyano-Trifluoromethylation of Alkenes and Alkynes

“…A copper-mediated halotrifluoromethylation of alkenes was reported by Jung, Han, and coworkers in 2015 using Umemoto reagent and a copper(I) halide salt, which would form a transition metal halide that generates the active CF 3 species and at the same time act as the halogen source ( Scheme 54 ) [ 78 ]. The main advantage of this approach is the high stability, commercial availability, and relatively low cost of copper halides.…”

Vicinal halo-trifluoromethylation of alkenes

“…Twenty-seven years later, this strategy associated with copper(0) catalysis applied by Ol'shevskaya and co-workers in the functionalization of allylcarboranes 26 and achieved the respective bromotri-uoromethylated carboranes 27 in high to excellent yields (Scheme 14b). 34 In 2015, Jung and Han demonstrated an efficient coppermediated bromotriuoromethylation of monosubstituted alkenes 28 using Umemoto's reagent 4 and CuBr, where CuBr acts as the source for both copper and bromine. 35 This reaction employed bis(pinacolato)diboron (B 2 pin 2 ) and K 2 HPO 4 as additives and MeCN as the solvent, leading to the production of various 1-CF 3 -2-Br-alkanes 29 in good to excellent yields (Scheme 15a).…”

“…Twenty-seven years later, this strategy associated with copper(0) catalysis applied by Ol'shevskaya and co-workers in the functionalization of allylcarboranes 26 and achieved the respective bromotrifluoromethylated carboranes 27 in high to excellent yields ( Scheme 14b ). 34 …”

Ligand‐Controlled, Tunable Copper‐Catalyzed Radical Divergent Trifluoromethylation of Unactivated Cycloalkenes

“…There is no doubt that the trifluoromethylation of olefin with concomitant introduction of other functional groups into molecular scaffolds is one of extremely efficient and economical methods [10] such as oxytrifluoromethylation, [11] aminotrifluoromethylation, [12] carbo‐trifluoromethylation, [13] thiotrifluoromethylation [14] and halotrifluoromethylation [15] . Regarding vicinal trifluoromethylated difunctionalization of alkene reactions, the construction of trifluoromethylated spirocycle via carbotrifluoromethylation reaction was rarely reported, [13a–f] but on the other hand, chlorotrifluoromethylation was generally realized by extremely active chlorine sources, for instance, CF 3 SO 2 Cl, [15a–f] TMS−Cl [15h] and dichloride sulfoxide [15i] as well as equivalent CuCl [15g] . We hypothesize that, if carbotrifluoromethylation and chlorotrifluoromethylation involving radical intermediates can be regulated in the similar catalytic system, divergent trifluoromethylation reactions should be easily available.…”