Direct C–H amination and C–H chloroamination of 7-deazapurines

Abstract

Selective methods for Pd and Cu-catalyzed C–H aminations and chloroaminations of 7-deazapurines were developed.

Synthesis of 8-(1,2,3-triazol-1-yl)-7-deazapurine nucleosides by azide–alkyne click reactions and direct C H bond functionalization

“…19,40–43 The examples include regioselective Pd-catalyzed direct C8-H arylation of the 6-phenyl-7-deazapurines with aryl halides to provide 8-arylated products albeit in low to moderate yields. 44 A regioselective direct C-H amination of the 7-deazapurines to give access to the 8-amino-, 45 or 7-amino-7-deazapurine analogues has been also reported. 46 We found that treatment of tubercidin 1b with benzotriazole (2 equiv.)…”

An Update on Direct C–H Bond Functionalization of Nitrogen-Containing Fused Heterocycles

“…In 2014, Hocek and co-workers also expanded the toolbox of C-H functionalization reactions of pyrrolo [2,3-d]pyrimidines by describing a Pd/Cu-mediated direct C-H amination and C-H chloroamination using N-alkyl-N-chloroarenesulfonamides as coupling partners (Scheme 57). 84 Based on related studies on indoles and after an extensive optimization, the conditions for C-H amination of heterocycles 146 turned out to be N-alkyl-N-chloroarenesulfonamide (3 equiv), Pd(OAc) 2 , Cu(acac) 2 , bpy, in the presence of a large excess of Na 2 CO 3 (7 equiv); the 6-aminated products 147 were obtained in moderate yields (41-68%). In this case, the regioselectivity observed was opposite to the first example of C-H amination since it occurred exclusively at C-6 of the pyrrolo [2,3-d]pyrimidine 146 suggesting a different mechanism.…”

Catalytic C–H bond functionalisation of purine and pyrimidine nucleosides: a synthetic and mechanistic perspective

“…A unique strategy for selective amination and chloroamination 51 of 7-deazapurines was recently disclosed by Hocek and co-workers 52 that allows easy access to a series of 6,8,9-tri-and 6,7,8,9-tetra- generally promoted by the addition of LiCl as the additive (source of chloro for the chlorination to take place at the C-7 position). Given the utility of highly substituted purines as bioactive molecules such a methodology emerges as a useful tool, although the lower reactivity could be addressed further.…”