Facile Synthesis of Thymidine Derivatives by Cross-Coupling of 5-Halogenouridine Derivatives with Trimethylaluminum

Abstract
An efficient method for the introduction of a methyl group in the 5-position of uridine derivatives is described. This method involves three steps: protection of 5-halogenouridines 4 and 5 with hexamethyldisilazane, a palladium-catalyzed cross-coupling of the pertrimethylsilylated nucleosides with trimethylaluminum, and subsequent deprotection to afford the corresponding thymidine derivatives 6 in high overall yields.

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