Regioselective arylation of uracil and 4-pyridone derivatives via copper(I) bromide mediated C–H bond activation

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

“…The authors found that the CuBr-mediated arylation of DMU 65 (R = H) with aryl iodides (2 equiv.) in the presence of t -BuOLi in DMF at reflux gave the C6-arylated derivatives 71 (R 1 = H) [61]. The 5-substituted DMU analogues 70 (R 1 = Me) afforded the 5,6-disubstituted derivatives 71 (R 1 = Me) but in lower yields (Scheme 24).…”

“…On the other hand, direct C-H arylation in the presence of CuI or in combination with Pd(OAc) 2 was hypothesized to proceed via an Ullmann-type mechanism [27,63], which involves the formation of a carbanion by the abstraction of the most acidic C6-H [64,65,66] in the uracil ring (e.g., 65 ) with base (path b ). Subsequent cupration, transmetallation and reductive elimination leading to the formation of C6 arylated uracil 67 [57,61]. Alternatively, addition of the copper center of the arylcopper(III) complex C to the more nucleophilic C5-position in 65 followed by either base-promoted anti -elimination or Heck-type syn β -hydrogen elimination has been also proposed for C6-arylation [61].…”

“…Subsequent cupration, transmetallation and reductive elimination leading to the formation of C6 arylated uracil 67 [57,61]. Alternatively, addition of the copper center of the arylcopper(III) complex C to the more nucleophilic C5-position in 65 followed by either base-promoted anti -elimination or Heck-type syn β -hydrogen elimination has been also proposed for C6-arylation [61]. Moreover, Heck-type carbopalladation of the 5,6-double bond of 65 with ArPdX species has been also considered for the arylation of uracil ring with aryl halides [59].…”

An easy direct arylation of 5-pyrazolones

“…However, it often needs pre-formation of halo-pyrazolones. Transition metal-catalyzed direct arylation of (hetero)arenes has emerged over the past few years as a rapidly growing field of syntheses [17–26]. The direct arylation of pyrazolones by using aryl halides offers a cleaner and more efficient method of meeting such goals and rare examples of such transformations have been described [15].…”

Novel Approaches for the Synthesis of C-5 Modified Pyrimidine Nucleosides

“…[80][81][82][83][84][85] It has been noted that both intra- [86][87][88] or intermolecularly 87,[89][90][91][92][93][94][95] direct arylations can proceed smoothly, especially with electron-rich heteroaromatics. 83 One of the advantages is that either organic halides or organometallic reagents can be substituted by simple arenes as partners in cross-coupling processes.…”