Palladium-Mediated Synthesis of C-5 Pyrimidine Nucleoside Thioethers from Disulfides and Mercurinucleosides

Article abstract of DOI:10.1021/jo00019a025

Thioether-linked side chains can be created at C-5 of pyrimidine nucleosides via a palladium-mediated reaction of mercurated nucleosides with organic disulfides. 5-(Chloromercuri)-2'-deoxyuridine reacts with butyl disulfide, phenyl disulfide, dimethyl 3,3'-dithiopropionate, and N,N'-bis(trifluoroacetyl)cystamine to yield respectively 5-(1-thiapentyl)-2'-deoxyuridine, 5-(phenylthio)-2'-deoxyuridine, 5-<3-(methoxycarbonyl)-1-thiapropyl>-2'-deoxyuridine, and 5-<3-(trifluoroacetamido)-1-thiapropyl>-2'-deoxyuridine in yields ranging from 46 to 73percent.Other mercurated nucleosides, including 5-(chloromercuri)-2'-deoxycytidine, 5-(chloromercuri)cytidine, and 5-(chloromercuri)tubercidin react with N,N'-bis(trifluoroacetyl)cystamine and lithium-palladium chloride in methanol to yield the corresponding coupled products, but the yields are much lower (5-10percent).The nucleoside coupling reaction is complicated by competing side reactions between disulfides and Pd²⁺, which remain to be elucidated