PAPER: Efficient N-arylation and N-alkenylation of the five DNA/RNA nucleobases

Jacobsen, M. F., Knudsen, M. M.; Gothelf, K. V.

J. Org. Chem. 2006, 71, 9183–9190, doi: 10.1021/jo061694i

Center for Catalysis and Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark

Abstract

A general approach to N-arylation and N-alkenylation of all five DNA/RNA nucleobases at the nitrogen atom normally attached to the sugar moiety in DNA or RNA has been developed. Various protected or masked nucleobases engaged readily in the copper-mediated Chan−Lam−Evans-modified Ullmann condensation with a range of different boronic acids at room temperature and were subsequently converted to the corresponding deprotected or unmasked adducts. Different N3-protecting groups were examined in the case of thymine, where the benzoyl group afforded the highest yields. A 4-alkylthio-substituted pyrimidin-2(1H)-one served as both a cytosine and a uracil precursor and was N-arylated and N-alkenylated in high yields. Adenine was efficiently and selectively N-arylated and N-alkenylated at the N9 position by employing a bis-Boc-protected adenine derivative, while a bis-Boc-protected 2-amino-6-chloropurine served as guanine precursor and could also be selectively N9-arylated and N9-alkenylated.

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