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

Abstract

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 α-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 α-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 C_sp³–Pd(O₂CR), a key intermediate, was generated through ionic ligand exchange between benzyl–Pd(NZ₂) 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_N2-type nucleophilic attack pathway.