Synthesis of α,α-Difluoro-β-amino Ketones from N-Boc-α-Amidosulfones and Pentafluoro-gem-diols.

To circumvent the synthesis and isolation of imines, a method was devised to construct α,α-difluoro-β-amino ketones from N-Boc-α-amidosulfones. The reactive nucleophiles, difluoroenolates, are generated in situ from the pentafluoro-gem-diols using cesium fluoride in pyridine. NMR studies confirm the role of the α-amidosulfones in this process. Incubation of the α,α-difluoro-β-amino ketones in rat serum demonstrates the relative stability of this structure as well as its value as a chemical probe or lead.