An Intramolecular Anionic Migration of a Stannyl Group from the 6-Position of 1-(2-Deoxy-d-erythro-pent-1-enofuranosyl)uracil to the 2′-Position: Synthesis of 2′-Substituted 1′,2′-Unsaturated Uridines

Abstract

Lithiation of 1-[3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-d-erythro-pent-1-enofuranosyl)uracil (1) takes place exclusively at the 6-position of the uracil base. The 6-tributylstannyl (or 6-trimethylsilyl) derivative prepared by quenching the C6-lithiated species with Bu3SnCl (or Me3SiCl) was found to undergo an intramolecular anionic migration to the 2′-positon of the furanoid glycal portion. By manipulation of the 2′-stannyl group, 2′-halogeno and 2′-carbon-substituted 1′,2′-unsaturated uridines were prepared for the first time. In contrast to the reported instability of 1 during deprotection, the 2′-substituted analogs synthesized in the present study gave the corresponding free nucleosides uniformly in high yields upon treatment with NH4F in MeOH.