Palladium-catalyzed cross-coupling is one of the most widely applied reaction classes in pharmaceutical research. The metal is adept at connecting aromatic rings to one another or to nitrogen centers. However, functional complexity can obstruct the reaction, necessitating laborious ligand optimization. Uehling et al. mitigated this problem by isolating the stable product of palladium's reaction with a complex aryl halide ahead of time. Subjecting these compounds to downstream coupling reactions substantially improved yields.Science, this issue p. 405Palladium-catalyzed cross-coupling reactions have transformed the exploration of chemical space in the search for materials, medicines, chemical probes, and other functional molecules. However, cross-coupling of densely functionalized substrates remains a major challenge. We devised an alternative approach using stoichiometric quantities of palladium oxidative addition complexes (OACs) derived from drugs or drug-like aryl halides as substrates. In most cases, cross-coupling reactions using OACs proceed under milder conditions and with higher success than the analogous catalytic reactions. OACs exhibit remarkable stability, maintaining their reactivity after months of benchtop storage under ambient conditions. We demonstrated the utility of OACs in a variety of experiments including automated nanomole-scale couplings between an OAC derived from rivaroxaban and hundreds of diverse nucleophiles, as well as the late-stage derivatization of the natural product k252a.