Copper-catalyzed oxidative trifluoromethylation of benzylic sp3 C–H bond adjacent to nitrogen in amines

Direct α‐Functionalization of Saturated Cyclic Amines

“…One such report is that of Li and Mitsudera, who described a highly efficient Cu-catalyzed protocol for the trifluoromethylation of the benzylic sp 3 C À H of tetrahydroisoquinolines. [62] The use of CF 3 www.chemeurj.org tron-withdrawing CF 3 group on the N-aryl. It was suggested that this might also be the explanation for the lack of product formation (167-169) observed with N-acyl and alkoxycarbonyl substrates 152 and 153.…”

Copper-Catalyzed Late-Stage Benzylic C(sp3)–H Trifluoromethylation

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] However, direct C(sp 3 )-H trifluoromethylation, which is most atom economical, remains a formidable challenge, and only a few examples have been reported to date. [14][15][16][17][18][19][20][21][22] In this context, allylic C(sp 3 )-H trifluoromethylation with Umemoto's reagent 23 or Togni's reagent 24 was reported by the groups of Liu 14 and Wang, 15 and benzylic C(sp 3 )-H trifluoromethylation of phenols and ortho-methyl-substituted phenylketones with Togni's reagent was described by Hamashima et al 16,17 These reactions proceed via the intermediacy of CF 3 radicals. Benzylic C(sp 3 )-H trifluoromethylation of pyridine and quinoline derivatives with Ruppert-Prakash reagent [25][26][27] was also known, which takes place via oxidation followed by nucleophilic CF 3 addition.…”

“…Benzylic C(sp 3 )-H trifluoromethylation of pyridine and quinoline derivatives with Ruppert-Prakash reagent [25][26][27] was also known, which takes place via oxidation followed by nucleophilic CF 3 addition. [18][19][20][21][22] The underdevelopment of C(sp 3 )-H trifluoromethylation should be largely attributed to the lack of methods for trifluoromethylation of alkyl radicals. [28][29][30] We recently introduced the trifluoromethylation of alkyl halides by reaction with (bpy)Cu(CF 3 ) 3 (bpy = 2,2 0 -bipyridine), K 2 S 2 O 8 , and Et 3 SiH in aqueous solution and proposed the mechanism of CF 3 transfer to alkyl radicals from Cu(II)-CF 3 intermediates.…”

Direct Trifluoromethylation of the CH Bond

“…Li and Mitsudera also reported a copper‐catalyzed trifluoromethylation of sp 3 CH bonds adjacent to a nitrogen atom (Scheme ) 27. The reactions of various tetrahydroisoquinoline derivatives gave the corresponding trifluoromethylated products in 15–90% yields under very mild conditions.…”