Substituents are often added to arenes by directed metalation, in which an existing substituent helps direct a metalating reagent to abstract hydrogen from a carbon on the ring. An electrophile can then be added to form a substituted product, typically ortho to the directing group. Meta substitutions, on the other hand, are difficult and rare. Chemists have been trying to get beyond this “ortho curse,” and researchers in Scotland have now made an advance that could help break the spell (Science 2014, DOI: 10.1126/science.1259662). Robert E. Mulvey, Charles T. O’Hara, and coworkers at the University of Strathclyde identified directing groups that allow a disodium-magnesium alkylamide reagent to metalate two arene sites, at either ortho and meta positions or at both meta positions relative to the directing group. The approach differs from conventional directed ortho metalation in that the reagent instead of the directing group exerts primary control over which ring positions are modified. “C–H bonds in positions previously inaccessible to metalation, and hence to functionalization, should now be accessible,” O’Hara says.