Photoredox‐Catalyzed Stereoselective Conversion of Alkynes into Tetrasubstituted Trifluoromethylated Alkenes

Abstract

Ar egio-and stereoselective synthesis of trifluoromethylated alkenes bearing four different substituents has been developed. Stereocontrolled sulfonyloxytrifluoromethylation of unsymmetric internal alkynes with an electrophilic CF 3 reagent, namely the triflate salt of the Yagupolskii-Umemoto reagent, in the presence of an Ir photoredoxc atalyst under visible-light irradiation afforded trifluoromethylalkenyl triflates with well-predictable stereochemistry resulting from anti addition of the trifluoromethyl and triflate groups.S ubsequent palladium-catalyzed cross-couplings led to tetrasubstituted trifluoromethylated alkenes in ah ighly stereoselective manner.The present method is the first example of afacile onepot synthesis of tetrasubstituted trifluoromethylated alkenes from simple alkynes. Angewandte Chemie 13115

Trifluoromethanesulfonic Anhydride as a Low‐Cost and Versatile Trifluoromethylation Reagent

“…Electron-poor substrates (1n, 1s, 1t)a fforded the products in slightly lower yields along with the recovery of some of the starting materials.H ighly electron-deficient heteroarenes such as pyridines and pyrazines displayed minimal reactivity.I mportantly,t he synthetically useful triflate (1e), boronate (1g, 1i, 1l), and bromide (1m)w ere all tolerated under the reaction conditions.R emarkably,t his method could be successfully applied to complex compound pentoxifylline (1w), thus demonstrating the potential utility of this reaction for latestage trifluoromethylation. To date,however, only Koike and Akita have reported the photoredox-catalyzed trifluoromethylation and triflation of alkynes, [20] but the more expensive S-(trifluoromethyl)diphenylsulfonium trifluoromethanesulfonate (Yagupolskii-Umemoto reagent) was used as aC F 3 source.T hus,t his reaction provides al ow-cost, atom-economical, and practical method for the preparation of tetrasubstituted trifluoromethylated alkenes. With aview to atom economy,wewondered whether both the CF 3 and OTf groups could be simultaneously introduced into organic molecules.I nspired by recent advances in the trifluoromethylation functionalization reaction of alkenes and alkynes, [19] internal alkynes were subjected to the photoredox trifluoromethylation (Scheme 3).…”

Synthesis of α‐Trifluoromethylated Ketones from Vinyl Triflates in the Absence of External Trifluoromethyl Sources

“…Vinyl triflates are valuable electrophiles for av ariety of transition-metal-catalyzed coupling reactions. [8] In comparison, their use in radical reactions has received less attention. [9,10] In 2010, for example,K im and co-workers reported that vinyl triflates react with activated alkyl halides to form aalkylated ketones (Scheme 2a).…”

Synthesis of α‐Trifluoromethylated Ketones from Vinyl Triflates in the Absence of External Trifluoromethyl Sources

“…[8] In comparison, their use in radical reactions has received less attention. [8] In comparison, their use in radical reactions has received less attention.…”