Radical trifluoromethylation has been emerging as a versatile tool for the synthesis of trifluoromethylated compounds that play increasingly important roles in pharmaceuticals, agrochemicals and materials science.

No abstract

Reported herein is an unprecedented protocol for trifluoromethylation of unactivated aliphatic C(sp3)−H bonds. With Cu(OTf)2 as the catalyst, the reaction of N‐fluoro‐substituted carboxamides (or sulfonamides) with Zn(CF3)2 complexes provides the corresponding δ‐trifluoromethylated carboxamides (or sulfonamides) in satisfactory yields under mild reaction conditions. A radical mechanism involving 1,5‐hydrogen atom transfer of N‐radicals followed by CF3‐transfer from CuII−CF3 complexes to the thus formed alkyl radicals is proposed.

We report herein an unprecedented protocol for aminotrifluoromethylation of alkenes. With Cu­(OTf)2 as the catalyst, the reaction of alkenes, (bpy)­Zn­(CF3)2, and N-fluorobis­(benzene­sulfonyl)­imide (NFSI) at room temperature provides the corresponding aminotrifluoro­methylation products in satisfactory yields with high regioselectivity opposite to those driven by CF3 radical addition. The method exhibits a broad substrate scope and wide functional group compatibility. A mechanism involving N-radical addition to alkenes followed by trifluoromethylation of alkyl radicals is proposed.

Summary of main observation and conclusionWe report herein the direct N‐trifluoromethylation of N‐H amides. Promoted by AgOTf and 2‐fluoropyridine, the reaction of a variety of amides with Selectfluor, TMSCF3 and CsF proceeds smoothly at room temperature leading to the corresponding N‐trifluoromethylated products in satisfactory yields. The protocol is also applicable to amino acid derivatives, resulting in efficient and chemoselective N‐trifluoromethylation of di‐ and tri‐peptides with retention of configuration. A mechanism involving reductive elimination of Ag(III) intermediates to form N—CF3 bonds is proposed.

The copper-catalyzed ring-opening C-trifluoromethylation of cycloalkanone oximes with Zn­(CF3)2 complexes is described. The reaction proceeds in dichloromethane under mild conditions, providing an efficient and general entry to γ- or δ-CF3-substituted nitriles via tandem N–O and C­(sp2)–C­(sp3) bond cleavage and C­(sp3)–CF3 bond formation. The protocol exhibits a broad substrate scope and wide functional group compatibility. A radical mechanism involving the CF3 transfer from Cu­(II)–CF3 complexes to alkyl radicals is proposed.

The copper-catalyzed reaction of arylcyclopropanes, N-fluorobis­(arenesulfonyl)­imides, and (bpy)­Zn­(CF3)2 (bpy = 2,2′-bipyridine) at room temperature affords the corresponding ring-opening 1,3-aminotrifluoromethylation products in satisfactory yields. The protocol is highly regioselective, providing a convenient entry to γ-trifluoromethylated amines. A mechanism involving the trifluoromethylation of benzyl radicals is proposed.

Reported herein is an unprecedented protocol for trifluoromethylation of unactivated aliphatic C(sp3)−H bonds. With Cu(OTf)2 as the catalyst, the reaction of N‐fluoro‐substituted carboxamides (or sulfonamides) with Zn(CF3)2 complexes provides the corresponding δ‐trifluoromethylated carboxamides (or sulfonamides) in satisfactory yields under mild reaction conditions. A radical mechanism involving 1,5‐hydrogen atom transfer of N‐radicals followed by CF3‐transfer from CuII−CF3 complexes to the thus formed alkyl radicals is proposed.