Pd-catalyzed amination as an alternative to nucleophilic aromatic substitution for the synthesis of N-alkyltacrines and analogues

A reliable Pd-catalyzed amination protocol is described for the synthesis of N-alkyltacrines and analogs. The Josiphos ligand CyPFtBu was found to provide optimum yields: 16 examples are given. Compared to the typical high-temperature nucleophilic aromatic substitution (NAS) routes, Pd-catalyzed aminations proceed at significantly lower reaction temperatures, and enable the synthesis of otherwise inaccessible products.