Synthesis of 5-fluorovinyl derivatives of pyrimidines via Suzuki–Miyaura coupling and their 1,3-dipolar cycloaddition reactions with nitrones

A simple two-step synthesis of a new class of fluorinated isoxazolidinyl derivatives of pyrimidine is described. The reactions proceed via the Suzuki–Miyaura coupling followed by highly regioselective 1,3-dipolar cycloaddition with nitrones. Removal of the pyrimidine protecting groups leads to a fluorinated isoxazolidine analogue of pseudouridine.

Graphical abstractA simple synthesis of a new class of fluorinated isoxazolidinyl derivatives of pyrimidine is described.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 5-Fluorovinylpyrimidines can be obtained at moderate yield by Suzuki–Miyaura cross-coupling. ► Synthesis of a new class of fluorinated isoxazolidinyl derivatives of pyrimidine via 1,3-dipolar cycloaddition is described. ► The mild acidic hydrolysis of isoxazolidinyl derivatives of 2,4-bis(alkoxy)-pyrimidine leads to fluorinated analogue of pseudouridine.