Fluorination of sulfanyl amides using difluoroiodoarene reagents

A range of sulfur-containing amides have been fluorinated with the hypervalent iodine difluoride reagents 1, and two principal reaction pathways identified. Cephalosporin esters 2 having a heteroatom in the alpha-position to sulfur undergo fluorination in DCM with cleavage of the carbon-sulfur bond to form novel fluorinated beta-lactams 4. Sulfides with electron-withdrawing groups in the alpha-position undergo alpha-fluorination in a process analogous to the classical Pummerer reaction. This Fluoro-Pummerer reaction has been exemplified for a range of simple alpha-phenylsulfanylacetamides 14-19. When beta-hydrogens are present in the substrate a different route is followed, with deprotonation by basic fluoride taking place to yield vinyl sulfides 41-43. When an excess of the fluorinating reagent is used these vinyl sulfides can undergo further reaction in a novel tandem Pummerer-Additive-Pummerer process to yield alpha,beta-difluoro sulfides 45-47.