Palladium-catalyzed intermolecular fluoroesterification of styrenes: exploration and mechanistic insight

A novel palladium-catalyzed intermolecular oxidative fluoroesterification of vinylarenes has been developed using NFSI, one of the mildest electrophilic fluorinating reagents. The reaction presents an efficient synthetic pathway to afford a series of alpha-monofluoromethylbenzyl carboxylates in good to excellent yields. Rather than following an electrophilic fluorination pathway, the reaction is initiated through oxidation of Pd(0) to a Pd(II) fluoride complex by NFSI, followed by fluoropalladation of a styrene to generate an alpha-monofluoromethylbenzyl-Pd intermediate. Generally, reductive elimination of benzyl-Pd-II complexes is favored with relatively strong oxy-nucleophiles to afford C-O bonds. This reaction, however, exhibited the opposite reactivity: strong acids with weak nucleophilicity, such as CF3CO2H and CCl3CO2H, were prone to afford the fluoroesterification product, while weak acids with strong nucleophilicity, such as HOAc and BzOH, did not deliver the C-O bond product. Further mechanistic studies determined that Csp(3)-Pd(O2CR), a key intermediate, was generated through ionic ligand exchange between benzyl-Pd(NZ(2)) and CF3CO2H, and the final C-O bond was possibly formed through reductive elimination of a high-valent C-sp3-Pd(O2CR) complex via an S(N)2-type nucleophilic attack pathway.