Pd-catalyzed versus uncatalyzedPhI(OAc)2-mediated cyclization reactions ofN6-(11’-biaryl-2-yl)adeninenucleosides

摘要

In this work we have assessed reactions of N⁶-([1,1’-biaryl]-2-yl)adenine nucleosides with Pd(OAc)2 and PhI(OAc)2, via a Pd^II/Pd^IV redox cycle. The substrates are readily obtained by Pd/Xantphos-catalyzed reaction of adenine nucleosides with 2-bromo-1,1’-biaryls. In PhMe, the N⁶-biarylyl nucleosides gave C6-carbazolyl nucleoside analogues by C–N bond formation with the exocyclic N⁶ nitrogen atom. In the solvent screening for the Pd-catalyzed reactions, an uncatalyzed process was found to be operational. It was observed that the carbazolyl products could also be obtained in the absence of a metal catalyst by reaction with PhI(OAc)2 in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Thus, under Pd catalysis and in HFIP, reactions proceed to provide carbazolyl nucleoside analogues, with some differences. If reactions of N⁶-biarylyl nucleoside substrates were conducted in MeCN, formation of aryl benzimidazopurinyl nucleoside derivatives was observed in many cases by C–N bond formationwith the N1 ring nitrogen atom of the purine (carbazole andbenzimidazole isomers are readily separated by chromatography). WhereasPd^II/Pd^IV redox is responsible for carbazole formationunder the metal-catalyzed conditions, in HFIP and MeCN radical cations and/ornitrenium ions can be intermediates. An extensive set of radical inhibitionexperiments was conducted and the data are presented.