The functionalization of diazines is of great importance, because these N-heterocycles are present in numerous natural products, pharmaceuticals, and agrochemicals. They also find applications in materials science and polymer chemistry. The directed metalation and further functionalization of these electron-deficient N-heterocycles can be realized with ate bases and in some cases with lithium bases. However, low temperature and carefully designed reaction conditions are required owing to the low stability of the resulting lithitated N-heterocycles. Recently, the C-H activation of various N-heteroaromatics has also been reported. Moreover, a range of LiCl-solubilized TMP–metal bases (TMP=2,2,6,6-tetramethylpiperidyl) are known. They display a high kinetic basicity and give access to several metalated diazines and purines. It was also found that these metallic amide bases are compatible with a strong Lewis acid, such as BF₃⋅OEt₂. Thus, the reactivity of the sterically hindered TMP base is not annihilated by BF₃⋅OEt₂, but on the contrary, a synergetic effect is observed (dual activation). This effect allows a regioselective metalation of various substituted pyridines and derivatives, which is not possible without the use of this Lewis pair combination. This compatibility of a strong Lewis acid with a Lewis base as a result of steric hindrance corresponds directly to the concept of frustrated Lewis pairs. Herein, we report a new BF₃-assisted regioselective metalation of biologically relevant pyrimidine derivatives and purines. As an application, we developed a new strategy for the BF₃-mediated regioselective full functionalization of pyrazines.