Purinyl N-Directed Aroylation of 6-Arylpurine Ribo- and 2’-Deoxyribonucleosides, and Mechanistic Insights

08 March 2024, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


The purinyl ring contains four embedded nitrogen atoms of varying basicities. Selective utilization of these ring nitrogen atoms can lead to relatively facile remote functionalization, yielding modified purinyl motifs that are otherwise not easily obtained. Herein, we report previously undescribed N-directed aroylation of 6-arylpurine ribo and the more labile 2’-deoxyribonucleosides. Kinetic isotope analysis as well as reaction with a well-defined dimeric, palladated 9-benzyl 6-arylpurine provided evidence for N-directed cyclometallation as a key step, with a plausible rate-limiting C–H bond cleavage. Radical inhibition experiments indicate the likely intermediacy of aroyl radicals. The chemistry surmounts difficulties often posed in the functionalization of polynitrogenated and polyoxygenated nucleosidic structures that possess complex reactivities and a labile glycosidic bond that is more sensitive in the 2’-deoxy substrates.


C–H bond activation
acyl radical

Supplementary materials

Supporting Information
Experimental procedures, characterization data, data for mechanistic studies, X-crystallographic data, copies of proton, carbon, deuterium, and fluorine NMR spectra.


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