Late-stage (radio)fluorination of alkyl phosphonates via electrophilic activation.

ABSTRACT: Constructing organic fluorophosphines, vital drug skeletons, through the direct fluorination of readily available alkyl phosphonates has been impeded due to the intrinsic low electrophilicity of P^V and the high bond energy of P═O bond. Here, alkyl phosphonates are electrophilically activated with triflic anhydride and N-heteroaromatic bases, enabling nucleophilic fluorination at room temperature to form fluorophosphines via reactive phosphine intermediates. This approach facilitates the late-stage (radio)fluorination of broad dialkyl and monoalkyl phosphonates. Monoalkyl phosphonates derived from targeted drugs, including cyclophosphamide, vortioxetine, and dihydrocholesterol, are effectively fluorinated, achieving notable yields of 47-71%. Radiofluorination of medically signifi

SUBMITTER: Zhang K 

PROVIDER: S-EPMC11604993 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature