Functionalization of Unprotected Uracil Derivatives Using the Halogen−Magnesium Exchange

The reaction of commercially available 5-iodouracil with 2 equiv of MeMgCl in the presence of LiCl, followed by the addition of i-PrMgCl·LiCl, provides the corresponding trimagnesiated species, which reacts with various electrophiles to give selectively 5-functionalized uracil derivatives. This method was also successfully applied to the functionalization of 6-iodouracils including the synthesis of pharmaceutically relevant Emivirine and HEPT precursors.