Efficient direct 2,2,2-trifluoroethylation of indoles via C–H functionalization

Abstract

A novel highly C3 selective metal free trifluoroethylation of indoles using 2,2,2-trifuoroethyl(mesityl)-iodonium triflate was developed. The methodology enables the introduction of a trifluoroethyl group in a fast and efficient reaction under mild conditions with high functional group tolerance. Beyond the synthetic developments, quantum chemical calculations provide a deeper understanding of the transformation.

Understanding and Exploitation of Neighboring Heteroatom Effect for the Mild N-Arylation of Heterocycles with Diaryliodonium Salts under Aqueous Conditions: A Theoretical and Experimental Mechanistic Study

“…23 For identifying the initial resting state we first focused on the possible solvated forms of the iodonium salt. Three conformations (depending on the equatorial ligand) and the dissociated form have been considered.…”

Palladium-Catalyzed Enantioselective Csp3–Csp3Cross-Coupling for the Synthesis of (Poly)fluorinated Chiral Building Blocks

“…Then the mixture was cooled again to 0 °C, followed an addition of a THF solution (7 mL) of mesityl(2,2,2-trifluoroethyl)-λ 3 -iodanyl trifluoromethanesulfonate 6 (2.1 g, 4.4 mmol, 1.3 equiv). After 2 hours stirring at room temperature, the mixture was quenched with aqueous solution of NH 4 Cl, extracted with Et 2 O, dried over Na 2 SO 4 , filtered, and concentrated in vacuo.…”

Copper‐Catalyzed Insertion into Heteroatom–Hydrogen Bonds with Trifluorodiazoalkanes

“…[1] Thei nstallation of a1 ,1,1-trifluoro-2l 3 -ethane (CF 3 CH 2 )f ragment onto arenes and heteroatoms has received less attention. [1] Thei nstallation of a1 ,1,1-trifluoro-2l 3 -ethane (CF 3 CH 2 )f ragment onto arenes and heteroatoms has received less attention.…”

“…[1] Thei nstallation of a1 ,1,1-trifluoro-2l 3 -ethane (CF 3 CH 2 )f ragment onto arenes and heteroatoms has received less attention. [3] More conventional approaches have been implemented for heteroatom trifluoroethylation:T he N-trifluoroethylation of anilines with an electrophilic hypervalent iodine CH 2 CF 3 reagent has been reported; [4] alternatively,t rifluoroacetaldehyde has been subjected to reductive amination. [3] More conventional approaches have been implemented for heteroatom trifluoroethylation:T he N-trifluoroethylation of anilines with an electrophilic hypervalent iodine CH 2 CF 3 reagent has been reported; [4] alternatively,t rifluoroacetaldehyde has been subjected to reductive amination.…”

“…Recent developments include crosscoupling reactions with CF 3 CH 2 Iunder Pd catalysis with aryl boronic acids, [2] or through CH arene functionalization. [5] The installation of branched trifluoroalkyl fragments of the type CF 3 CHR is more challenging,e specially when enantioselectivity is required. [5] The installation of branched trifluoroalkyl fragments of the type CF 3 CHR is more challenging,e specially when enantioselectivity is required.…”