A Versatile Synthesis of Fluorinated Uracils in Solution and on Solid-Phase

An efficient and convenient two-step synthesis of new fluorinated uracils is described. The first step involves the condensation of an ester enolate with a fluorinated nitrile to furnish fluorinated β-enamino esters. In turn, these compounds react with organic isocyanates or isothiocyanates to give C-6 fluorinated uracils or thiouracils, respectively, in excellent yields. This synthesis has been successfully adapted to solid-phase conditions with high diversity, thereby facilitating the creation of small (thio)uracil libraries.