Synthesis of C-5 substituted nucleosides via palladium-catalyzed coupling of dienes and amines

Abstract

The palladium-catalyzed coupling of C-5 iodopyrimidine nucleosides; 1,2-, 1,3-, or 1,ω-dienes; and amines provides a novel and efficient method for the preparation of a wide variety of C-5 aminoalkyl-substituted nucleosides. Adding certain Lewis acids, particularly zinc salts, improves the yields significantly. Secondary amines are the most effective amines for this process. Acyclic and cyclic dienes have been successfully employed. Protection of the 3′- and 5′-hydroxyl groups of iodouridine is required in order to obtain good yields when the coupling process is carried out on 1,3-dienes or long chain or branched non-conjugated dienes.