Selective Nucleophilic Fluoroalkylations Facilitated by Removable Activation Groups

Selective incorporation of fluorine atoms or fluorine-containing moieties into organic molecules has become a routine and powerful strategy in drug design and new functional-material development. Nucleophilic fluoroalkylation, typically involving the transfer of a fluorinated carbanion or carbanion equivalent to an electrophile, is one of the most important and frequently used methods to synthesize fluorinated organic molecules. In this Account, we introduce some recent achievements in the field of nucleophilic di- and monofluoroalkylation chemistry with functionalized fluoroalkylation reagents. In particular, the effect of fluorine substitution on the reactivity of carbanions is discussed, and several strategies for improving nucleophilic fluoroalkylations are proposed and successfully applied in various new nucleophilic fluoroalkylation reactions. It was found that attaching a removable activation group (such as the phenylsulfonyl group) to a fluorinated carbanion is an important approach to improve the latter's reactivity.