Functionalization of 2H-1,2,3-Triazole C-Nucleoside Template via N(2) Selective Arylation

• Published in: Journal of organic chemistry Vol. 81; no. 11; pp. 4540 - 4549
• Main Authors: Lopes, Alexandra Basilio, Wagner, Patrick, de Souza, Rodrigo Octavio Mendonça Alves, Germain, Nadège Lubin, Uziel, Jacques, Bourguignon, Jean-Jacques, Schmitt, Martine, Miranda, Leandro S M
• Format: Journal Article
• Language: English
• Published: United States 03.06.2016
• ISSN: 1520-6904
• DOI: 10.1021/acs.joc.6b00323

C-Nucleosides are an underexplored and important class of nucleosides with antiviral and anticancer activity. In addition, triazole heterocycles are well employed as a strategy to modify nucleobase in nucleoside analogues, although rare examples were described for triazoyl C-nucleosides. N(2)-Aryl-1,2,3-triazole C-nucleoside compounds that could be obtained by selective 1,2,3-triazole heterocycle N(2) arylation in 1-β-d-ribofuranosyl-2H-1,2,3-triazole substrate were designed in this study. The optimized condition used AdBrettPhos/[PdCl(allyl)]2 as the catalyst system. This transformation was accomplished by aryl halides bearing an electron donor and withdrawing groups, as well as by heterocyclic halides in good to excellent yields. The transformation developed in this study represents a significant contribution to the nucleoside field, once it allows for the synthesis of unexplored scaffolds through selective functionalization of triazole nucleosides.