An alternative method for the synthesis of 2'-halogeno-1',2'-unsaturated uridine derivatives through syn-elimination of pivalic acid of 2'-halogeno- 2'-deoxy-1'-pivaloyloxyuracil nucleoside: preparation of its 2'-C-branched nucleosides.

An alternative method for the preparation of 2'-bromo- (5b) and 2'-iodo- (5c) 1',2'-unsaturated uracil nucleosides has been developed. The protocol was on the basis of the syn-elimination of pivalic acid from 2'-bromo-(7a,b) and 2'-iodo-(9a,b) 1'-pivaloyloxy-2'-deoxyuridine derivatives, which were derived from the halo-pivaloyloxylation of 3',5'-bis-O-TBDMS-1',2'-unsaturated uridine 1. Compounds 5b and 5c were shown to serve as versatile synthons for the respective 2'-C-branched 1',2'-unsaturated uracil nucleosides, through palladium-catalyzed cross-coupling or halogen-lithium exchange reactions.