Organofluorine compounds are prevalent in the pharmaceutical and agrochemical industries as a result of the unique properties which can be introduced by a C–F bond. Accordingly, methods for C–F bond formation are highly sought after in the chemistry community and continue to advance. Deoxyfluorination is an attractive approach owing to the fact that alcohol starting materials are inexpensive and readily available. Whilst deoxyfluorination can be achieved by nucleophilic displacement of a suitable leaving group with a metal fluoride, efforts have focused on the development of costly bespoke reagents such as diethylaminosulfur trifluoride (DAST), PhenoFluor, and PyFluor in order to circumvent the issues associated with metal fluorides (highly solvated, basic, high lattice energies, and poor solubility in organic solvents). We present a deoxyfluorination strategy which employs commodity reagents (N,N’-diisopropylcarbodiimide (DIC) and CuF2) that overcome the limitations of metal fluorides. The activation of alcohols into O-alkylisoureas in situ enables chelation of the metal fluoride, resulting in a stereospecific and intramolecular delivery of fluoride which is evidenced through spectroscopic studies and control reactions. Herein we report a novel and operationally simple protocol utilizing the inexpensive and atypical fluoride source, CuF2, allowing stereospecific access to fluorinated products in good to excellent yields, with medicinally relevant examples included. In addition, the compatibility of our strategy in 18F radiolabeling for positron emission tomography (PET) imaging applications will be discussed.

Copper-mediated stereospecific intramolecular deoxyfluorination using CuF2

2019 Fall National Meeting

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