Stereoselective Synthesis of α-Fluoro-γ-nitro Thioesters under Organocatalytic Conditions.

Fluorinated monothiomalonates (F-MTMs) were used as building blocks for the stereoselective synthesis of organofluorine compounds. We present conjugate addition reactions between F-MTMs with nitroolefins that proceed under mild organocatalytic conditions and provide access to α-fluoro-γ-nitro thioesters with adjacent tetrasubstituted and tertiary stereogenic centers. Only 1 mol % of a cinchona alkaloid-urea catalyst is necessary to obtain the addition products in excellent yields and stereoselectivities. The methodology allowed for the straightforward synthesis of a fluorinated analogue of the PAR-2 agonist AC-264613.