First cross-coupling reactions on halogenated 1H-1,2,4-triazole nucleosides

摘要

The halogenated 1H-1,2,4-triazole glycosides 6-10 were synthesized by BF3-activated glycosylation of 3(5)-chloro-1,2,4-triazole (2), 3,5-dichloro-1,2,4-triazole (3), 3,5-dibromo-1,2,4-triazole (4), and 3(5)-bromo-5(3)-chloro-1,2,4-triazole (5) with 1,2,3,4-tetra-O-pivaloyl-beta-D-xylopyranose (1). The beta-anomeric major products 3-chloro-1-(2,3,4-tri-O-pivaloyl-beta-D-xylopyranosyl)-1,2,4-triazole (6 beta), 3,5-dichloro-1-(2,3,4-tri-O-pivaloyl-beta-D-xylopyranosyl)-1,2,4-triazole (7 beta), and 3,5-dibromo-1-(2,3,4-tri-O-pivaloyl-beta-D-xylopyranosyl)1,2,4-triazole (8 beta) were used as starting materials for transition metal catalyzed C-C-coupling reactions. Arylations of the triazole ring of 7 beta, and 8 beta were successful in 5-position with phenylboronic acid, 4-vinylphenylboronic acid, and 4-methoxyphenylboronic acid, respectively, under Suzuki cross-coupling conditions (products 11-17). Moreover, a Cu-catalyzed perfluoroalkylation of 8 beta is reported with 1-iodo-perfluorohexane yielding 3-perfluorohexyl-1-(2,3,4-tri-0-pivaloyl-beta-D-xylopyranosyl)-1,2,4-triazole (18). Compound 18 was depivaloylated to the trihydroxy derivative 19. The copper-mediated reaction of 8 beta with Rupert's reagent gave the bis(3-bromo-1-(2,3,4-tri-0-pivaloyl-beta-D-xylopyranosyl)-1,2,4-triazol-5-yl) (20). beta 2006 Elsevier Ltd. All rights reserved.