Issue 33, 2024

Purinyl N-directed aroylation of 6-arylpurine ribo- and 2′-deoxyribonucleosides, and mechanistic insights

Abstract

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.

Graphical abstract: Purinyl N-directed aroylation of 6-arylpurine ribo- and 2′-deoxyribonucleosides, and mechanistic insights

Supplementary files

Article information

Article type
Paper
Submitted
28 Apr 2024
Accepted
13 Jun 2024
First published
13 Jun 2024

Org. Biomol. Chem., 2024,22, 6718-6726

Purinyl N-directed aroylation of 6-arylpurine ribo- and 2′-deoxyribonucleosides, and mechanistic insights

M. K. Lakshman, C. T. Malinchak, N. Shank, M. C. Neary and L. Stahl, Org. Biomol. Chem., 2024, 22, 6718 DOI: 10.1039/D4OB00689E

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