Catalytic C–H α-Trifluoromethylation of α,β-Unsaturated Carbonyl Compounds

Abstract

A copper(I)-catalyzed, regioselective C-H α-trifluoromethylation of α,β-unsaturated carbonyl compounds using Togni's reagent was developed. Diverse substrates, including enones as well as α,β-unsaturated esters, thioesters, and amides, stereospecifically afforded the corresponding (E)-α-trifluoromethylated products in moderate to high yields. Further, this method was applied to the C-H trifluoromethylation of drugs.

Olefinic C–H functionalization through radical alkenylation

“…Alkyenyl C-H trifluoromethylation utilizing Togni's reagent as the CF 3 radical precursor has been developed over the past years (Scheme 24). 31,32 However, only electron deficient internal alkenes were suitable in these transformations. Alternatively, CF 3 radicals could also be generated from the oxidation of nucleophilic trifluoromethylation reagents (CF 3 À ) by oxidants.…”

Radiosynthesis of the anticancer nucleoside analogue Trifluridine using an automated 18F-trifluoromethylation procedure

“…The most efficient synthetic routes towards non-radioactive TFT involve the direct trifluoromethylation of 2′-deoxyuridine, using reagents that generate radical intermediates, such as the Togni 34 and Langlois 35 reagents. As yet, there are no radiolabelled derivatives of such reagents for 18 F-trifluoromethylation.…”

Electrophilic trifluoromethylation of carbonyl compounds and their nitrogen derivatives under copper catalysis

“…Protocols for the direct introduction of a CF 3 group to the double bond of α,β-unsaturated carbonyl derivatives remain rare, 28 electrophilic species being expected to react at the more electron rich α-position of the deactivated double bond. Bi and co-workers 29 have developed a relatively general method employing a combination of Togni reagent 1 and copper iodide (10 mol%) in DMF that allows an entry into α-(E)-trifluoromethylated conjugated enones, esters, thioesters, and amides 27 with a total (E)-selectivity (Scheme 11). Again, it is believed that this reaction proceeds via a radical mechanism involving CF 3 radical addition to the conjugated ketone.…”