First Fluorous Synthesis of Fluorinated Uracils

Abstract

AbstractThis paper describes a novel fluorous synthesis of fluorinated uracils 4. In this new protocol, fluorous alcohols 1, which are used as fluorous tags, are acetylated to yield acetates 2, which in turn are treated with a base to form their enolates. These are then reacted with fluorinated nitriles to furnish tagged β‐enamino esters 3. Although this condensation step had been performed easily in previous solution and solid‐phase syntheses, it proved to be very elusive in the fluorous version. Meticulous control of the reaction conditions was thus essential in order to achieve satisfactory yields of β‐enamino esters 3. The final treatment of compounds 3 with isocyanates or isothiocyanates efficiently afforded uracils 4 with concomitant elimination of the fluorous tag, thereby facilitating the preparation of a small library of these derivatives.