C-H Trifluoromethylations of 1,3-Dimethyluracil and Reactivity of the Products in C-H Arylations

Modification of Purine and Pyrimidine Nucleosides by Direct C-H Bond Activation

“…Recently, C5-H trifluoromethylation of DMU 65 by means of electrophilic, nucleophilic or radical “CF 3 ” species in an effort to synthesize 6-aryl-5-(trifluoromethyl)uracils (e.g, 96 ) by direct activations of both C5-H and C6-H bonds in consecutive manner has been attempted (Scheme 35) [79]. Thus, reactions of 65 with electrophilic (Umemoto's or Togni’s) or nucleophilic (Rupert’s) reagents in combination with Pd or Cu catalyst either failed or led to the formation of 5,5- or 5,6-dimeric products or 5-CF 3 product in low yields.…”

“…Thus, reactions of 65 with electrophilic (Umemoto's or Togni’s) or nucleophilic (Rupert’s) reagents in combination with Pd or Cu catalyst either failed or led to the formation of 5,5- or 5,6-dimeric products or 5-CF 3 product in low yields. However, radical trifluoromethylation of 65 with sodium trifluoromethanesulfinate in the presence of tert -butyl hydroperoxide provided 1,3-dimethyl-5-(trifluoromethyl)uracil 95 in 67% yield [79]. The subsequent direct arylation at C6-H of 95 with 4-iodotoluene in the presence of Pd(OAc) 2 and CuI/CsF afforded desired 5,6-disubstituted uracils 96 albeit in low yield (25%); probably because of the electron-withdrawing effect of the CF 3 group at the 5 position on the pyrimidine ring.…”