FRUSTRATED LEWIS PAIR-MEDIATED SELECTIVE C–F BOND ACTIVATION AND SUBSEQUENT POST-FUNCTIONALIZATION OF POLYFLUOROALKANES

Abstract

Mono and difluoromethyl groups are emerging as valuable motifs in organic and material chemistries and are present in several agrochemicals, materials, and pharmaceuticals. The inclusion of fluorine in such molecules is attractive to enhance solubility, biological activity, chemical resistivity, thermal stability and to act as a spectroscopic probe. Thus, direct access of these fluorine compounds is highly desirable from commercially available polyfluorides. However, polyfluoromethyl groups generally suffer from ‘over-reaction’, where multiple C-F bonds are uncontrollably functionalized. We have developed a Frustrated Lewis Pair (FLP) mediated C-F bond activation which allows selective monodefluorination of polyfluoroalkanes via base capture of intermediate fluorocarbocations. This methodology can be applied to aromatic, heteroaromatic and non-aromatic polyfluorides to generate monoselectively fluoride substituted phosphonium, sulfonium and pyridinium salts. These salts can be further functionalized via Wittig coupling, nucleophilic substitution, photoredox alkylation, and cross-coupling reactions to install a range of functional groups into the activated C-F position.