Enantioselective C–H Activation for the Construction of Chiral Tertiary Fluorides via Migrative Carbofluorination

Construction of α-chiral centers via enantioselective C(sp³)-H activation of the isobutyric acid scaffold has emerged as a new chiral technology. However, this approach has not been compatible with the presence of α-fluorine, which prevented the access to fluorine-bearing α-chiral centers which are highly valuable in drug discovery. Here, we report a palladium-catalyzed asymmetric β-C(sp³)-H activation of the <i>gem</i>-dimethyl motif, followed by a dyotropic rearrangement that installs fluoro and aryl groups at the α- and β-positions, respectively. Using a bifunctional chiral monoprotected amino sulfonamide (MPASA) ligand, this method affords chiral tertiary fluorides with high reactivity and enantioselectivity, enabling access to desirable motifs in drug discovery.