It is quite rare to find 6-substituted pyrimidines in nature due to the difficulty involved in directly introducing a substituent to the 6-position whereas other synthetic analogues of naturally occurring nucleosides like 5-substituted derivatives are more common.
The aim was to synthesize 3',5'-O,O-bis(tert-butyldimethylsilyl)-6-phenyl-2'-deoxyuridine by carrying out a direct nucleophilic substitution of 3',5'-O,O-bis(tert-butyldimethylsilyl)-6-cyano-2'-deoxyuridine with the Grignard reagent: phenyl magnesium bromide in the presence of zinc (II) chloride catalyst.
The first step was silylation of commercially available 2'-deoxyuridine and subsequent bromination at the 5-position to give 3',5'-O,O-bis(tert-butyldimethylsilyl)-5-bromo-2'-deoxyuridine. This was reacted with the nucleophile KCN to yield a product with the cyano substitute at the 6-position via intramolecular nucleophilic substitution. The final step was to introduce an aryl substituent to the 6-position to yield the target molecule.
