Direct C–H borylation and C–H arylation of pyrrolo[2,3-d]pyrimidines: synthesis of 6,8-disubstituted 7-deazapurines

Abstract

Novel direct C-H borylations of 7-deazapurines to position 8 by B2pin2 under Ir catalysis were followed by Suzuki cross-couplings with aryl halides and other functional group transformations to give diverse 8-substituted 7-deazaadenines.

Switching the Regioselectivity of Direct C–H Arylation of 1,3‐Dimethyluracil

“…[11] In order to extend the use of C-H arylations in nucleoside/nucleic acid chemistry, we have tried to develop the C-H arylation of 1,3-dimethyluracil as a model compound for uracil bases and nucleosides. So far, only one example of an intramolecular C-H arylation of related compounds that leads to fused heterocycles has been reported, [12] during the course of our study.…”

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.)…”

Chemoselective Synthesis of 4,5‐Diarylpyrrolo[2,3‐d]pyrimidines (6,7‐Diaryl‐7‐deazapurines) by Consecutive Suzuki and Liebeskind–Srogl Cross‐Couplings

“…[13] Moreover, the attempted Liebeskind-Srogl reactions of 4-aryl-5-(phenylsulfanyl)pyrrolo [2,3-d]pyrimidine did not proceed at all, [14] and C-H arylation of 4-arylpyrrolo [2,3-d]pyrimidines proceeded at position 6. [15] Inspired by our previous work on orthogonal cross-coupling disubstitutions of pyrimidines, [16] we envisaged the combination of LiebeskindSrogl [17] and Suzuki [18] couplings as suitable for this purpose.…”