Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

Abstract

Regioselective conjugate 1,4-trifluoromethylation of α,β-unsaturated ketones by the use of shelf-stable electrophilic trifluoromethylating reagents, S-(trifluoromethyl)diphenylsulfonium salts and copper under mild conditions is described. A wide range of acyclic aryl-aryl-enones and aryl-alkyl-enones were converted into β-trifluoromethylated ketones in low to moderate yields. 2189Scheme 1: Trifluoromethylation of α,β-unsaturated ketones.

1,4-Addition of the CF3 group, perfluoroalkyl groups and functionalized difluoromethylated moieties: An overview

“…19 The authors used Cu 0 along with the S-(trifluoromethyl)diphenylsulfonium salt 25 as a CF 3 source in a -trifluoromethylated ketones 27a-h. The reaction was applied to several chalcones and the corresponding products were obtained in low to moderate yields (Scheme 8).…”

Recent Advances in Trifluoromethylation Reactions with Electrophilic Trifluoromethylating Reagents

“…The authors postulated a reaction mechanism involving radical species arising from one-electron reduction of 2 a in the presence of copper, affording CF 3 radicals (Scheme 34). [51] The CF 3 radicals are reduced by Cu, affording the nucleophilic CuCF 3 species which provides the 1,4-CF 3 adduct (Scheme 33) in low to moderate yield. Although the true reactive species including CF 3 radical and/or CuCF 3 are not clear, the naked CF 3 radical should be ruled out since high regioselectivity was observed.…”

Recent Advances in the One‐Step Synthesis of Distally Fluorinated Ketones

“…β‐Trifluoromethyl ketones are difficult to prepare because direct nucleophilic trifluoromethylation of α,β‐unsaturated ketones typically undergo 1,2‐addition rather than 1,4‐addition, affording trifluoromethyl allylic alcohols . Although in some particular cases, 1,4‐nucleophilic trifluoromethylation could be achieved, direct 1,4‐addition of CF 3 − anion to conventional α,β‐unsaturated ketones has rarely been reported, presumably due to the hardness of the CF 3 group …”