Suzuki-Miyaura and Mizoroki-Heck reactions play a key role. In fact, they have become the preferred method of CC bond formation, representing more than 30% of the total number of chemical transformations in the medicinal chemistry field. [3] Diverse metal-based catalytic systems have been designed since their discovery, involving the use of different sources of nickel, copper, cobalt, gold and, the most used, palladium. [4] However, the implementation of Pd-based catalytic systems is sometimes difficult due to the common inactivation of the catalyst, lixiviation of metal centers, and the subsequent contamination of the final products. [5] As a consequence of these drawbacks, the catalytic loadings of typical Mizoroki-Heck and Suzuki-Miyaura cross-couplings are relatively high, which implies an economical and environmental problem. [6] For all these reasons, the design of more and more reusable and stable Pd-based catalytic systems is increasingly in vogue. [1] One of the most powerful tools to achieve these goals consist of the use of heterogeneous catalysts, [7] such as zeolites, [8] metal organic frameworks (MOFs), [9] PEG derivatives, [10] conjugated microporous polymers (CMPs), [11] porous organic polymers (POPs), [12] and covalent organic framework (COFs). [13,14] Among the heterogeneous catalysis strategies, covalent organic frameworks have become one of the most promising materials in a wide range of areas [13,14] such as artificial photosynthesis, [15] photocatalysis for organic synthesis, [16,17] photocatalytic degradation of pollutants, [18,19] metal catalysis, [20] and confined organocatalysis. [21] They are quite versatile, because of the possibility of tuning their structure, functionality, and pore size, depending on the designable building blocks of which they are composed of. [22] Following this line, COFs have been used as platforms for the incorporation of Pd centers following different strategies (Figure 1, left): predesign of pending arms in the constitutive building blocks (a), functionalization with Pd-NPs (b), and, the more explored, coordination to the iminic nitrogens of the COF backbone (c). [23] First, the superficial functionalization of COFs and other related porous materials with highly active Pd(0) nanoparticles has been extensively explored. [24][25][26] However, coordination of single atom Pd(II) centers using COFs is a more challenging goal. One strategy to immobilize Pd(II) atoms consists of The phenanthroline unit in an imine-based covalent organic framework (Phen-COF) offers a robust coordination site for Pd(OAc) 2 centers. Coordination of palladium centers is demonstrated by a variety of techniques, including X-ray photoelectron spectroscopy and total X-ray fluorescence. The stable phenanthroline-Pd(II) coordination avoids leaching of metal centers to the reaction medium, where deactivation processes through nanoparticle formation limits the catalytic activities observed for homogeneous systems. Thus, because of isolation and immobilization of catalytic sites in the Pd@Phen-...