The site-selective C-H bond fluorination of complex natural products is one of the more sought-after transformations in organic and medicinal chemistry. In many radical-based fluorinations, however, a tempest of poor regio- and stereoselectivity, multiple additions of fluorine, and difficult separations of products conspire to make selective monofluorination appear out of reach. In our fluorination of the antibiotic ionophore salinomycin and its simple derivatives, however, a chain of discoveries, including an unanticipated skeletal rearrangement, provided us a tortuous but unique path to a very selective result, unlocking low-noise conformational reporting by F NMR in a widely studied medicinal scaffold.