Deuterium-labeled compounds find wide applications in kinetic studies, and within the pharmaceutical industry.A ne asily removable pyrimidine-baseda uxiliary has been employedf or the meta-CÀHd euteration of arenes. The scope of this Pd-catalyzedd euteration using commerciallya vailable[ D 1 ]-and[ D 4 ]-acetic acid has been demonstrated by its application in phenylacetic acid and phenylmethanesulfonate derivatives. Ad etailed mechanistic study led us to explore the reversibility of the non-rate determining CÀHa ctivation step. The presents tudy of meta-deuteriumi ncorporation illustrates the template morphology in terms of selectivity.T he applicability of this method has been demonstrated by the selective deuterium incorporation into various pharmaceuticals.

The incorporation of kinetically inert metal ions as structural elements in crystalline coordination polymers is a synthetic challenge. While a small family of materials based on inert ions has been prepared (i.e. Cr(III)-based MIL-100, and [Ru6(btc)4Cl3]), general strategies that enable reticular synthesis have not been reported. Here we describe the mechanochemical synthesis of a reticular family of crystalline Ru2[II,III]-based materials by polymerization of molecular Ru2 complexes, featuring unprotected carboxylic acid substituents, with Cu(OAc)2. The resulting crystalline heterobimetallic MOFs are solid-solutions of Ru2 and Cu2 sites housed within [M3L2] phases. The developed mechanochemical strategy is modular and allows for control of the primary coordination sphere of the Ru2 sites. We anticipate the strategy will provide a rational approach to incorporation of kinetically inert ions in porous crystalline coordination networks, generating a class of atomically precise mixed-metal materials.Reticular synthetic logic, in which systematic perturbation of molecular structures gives rise to predictable variation in materials properties, underpins the rational synthesis of metal-organic frameworks (MOFs). [1] Solvothermal syntheses often yield crystalline materials when metal ions that participate in facile ligand exchange chemistry ( " # $ >~0.04 s -1 at 298 K) are employed, [2][3] because reversible metal-ligand (M-L) bond formation enables crystallization defects to be annealed (Figure 1a). Incorporation of kinetically inert metal ions as structural elements in crystalline MOFs is a synthetic challenge, [4] and as a result, kinetically inert metal ions, which display slow M-L exchange (i.e. " # $ <~0.04 s -1 at 298 K, such as Cr(III), Ru(II or III), Rh(III), Ir(III), and Pt(II)) are rarely encountered in MOFs (Figure 1b). Notable exceptions include Cr(III)-based MIL-100, [5] MIL-101, [6] and [Ru6(btc)4Cl3] (btc = benzene-1,3,5-tricarboxylate), [7] all of which were synthesized at high temperature (≥160 °C), in presence of high concentrations of acid modulators, and obtained only as microcrystalline powders. These observations belie the inherent challenge of crystallization of coordination polymers based on slowly exchanging M-L bonds. Reductive labilization-metathesis strategies have been advanced as an approach to incorporate kinetically inert metal ions, [4] but application of these methods requires that fast ligand exchange kinetics are characteristic of one of the isolable oxidation states of the targeted ions.

The development of homogeneous catalysis is enabled by the availability of a rich toolkit of kinetics experiments, such as the Hg-drop test, that differentiate catalytic activity at ligand-supported metal complexes from potential heterogeneous catalysts derived from the decomposition of molecular species. Metal−organic frameworks (MOFs) have garnered significant attention as platforms for catalysis at site-isolated, interstitial catalyst sites. Unlike homogeneous catalysis, a relatively few strategies have been advanced to evaluate the origin of catalytic activity in MOF-promoted reactions. Many of the MOFs that have been examined as potential catalysts are composed of molecular constituents that represent viable catalysts in the absence of the extended MOF lattice, and thus interfacial sites and leached homogeneous species represent potential sources of catalyst activity. Here, we demonstrate that the analysis of deuterium kinetic isotope effects (KIEs) and olefin epoxidation diastereoselectivity provides probes of the origin of catalytic activity in MOF-promoted oxidation reactions. These analyses support the involvement of lattice-based Fe sites in the turnover-limiting step of C−H activation with Fe-MOF-74-based materials (i.e., the MOF functions as a bona fide catalyst) and indicate that Cu 2 -based MOF MIL-125-Cu 2 O 2 functions as a solid-state initiator for solution-phase oxidation chemistry and is not involved in the turnover-limiting step (i.e., the MOF does not function as a catalyst for substrate functionalization). We anticipate that the simple experiments described here will provide a valuable tool for clarifying the role of MOFs in C−H oxidation reactions.

The incorporation of kinetically inert metal ions as structural elements in crystalline coordination polymers is a synthetic challenge. While a small family of materials based on inert ions has been prepared (i.e. Cr(III)-based MIL-100, and [Ru6(btc)4Cl3]), general strategies that enable reticular synthesis have not been reported. Here we describe the mechanochemical synthesis of a reticular family of crystalline Ru2[II,III]-based materials by polymerization of molecular Ru2 complexes, featuring unprotected carboxylic acid substituents, with Cu(OAc)2. The resulting crystalline heterobimetallic MOFs are solid-solutions of Ru2 and Cu2 sites housed within [M3L2] phases. The developed mechanochemical strategy is modular and allows for control of the primary coordination sphere of the Ru2 sites. We anticipate the strategy will provide a rational approach to incorporation of kinetically inert ions in porous crystalline coordination networks, generating a class of atomically precise mixed-metal materials.Reticular synthetic logic, in which systematic perturbation of molecular structures gives rise to predictable variation in materials properties, underpins the rational synthesis of metal-organic frameworks (MOFs). [1] Solvothermal syntheses often yield crystalline materials when metal ions that participate in facile ligand exchange chemistry ( " # $ >~0.04 s -1 at 298 K) are employed, [2][3] because reversible metal-ligand (M-L) bond formation enables crystallization defects to be annealed (Figure 1a). Incorporation of kinetically inert metal ions as structural elements in crystalline MOFs is a synthetic challenge, [4] and as a result, kinetically inert metal ions, which display slow M-L exchange (i.e. " # $ <~0.04 s -1 at 298 K, such as Cr(III), Ru(II or III), Rh(III), Ir(III), and Pt(II)) are rarely encountered in MOFs (Figure 1b). Notable exceptions include Cr(III)-based MIL-100, [5] MIL-101, [6] and [Ru6(btc)4Cl3] (btc = benzene-1,3,5-tricarboxylate), [7] all of which were synthesized at high temperature (≥160 °C), in presence of high concentrations of acid modulators, and obtained only as microcrystalline powders. These observations belie the inherent challenge of crystallization of coordination polymers based on slowly exchanging M-L bonds. Reductive labilization-metathesis strategies have been advanced as an approach to incorporate kinetically inert metal ions, [4] but application of these methods requires that fast ligand exchange kinetics are characteristic of one of the isolable oxidation states of the targeted ions.

The incorporation of kinetically inert metal ions as structural elements in crystalline coordination polymers is a synthetic challenge. While a small family of materials based on inert ions has been prepared (<i>i.e.</i> Cr(III)-based MIL-100, MIL-101, and [Ru₆(btc)₄Cl₃]), general strategies that enable reticular synthesis have not been reported. Here we describe the mechanochemical synthesis of a reticular family of crystalline Ru₂[II,III]-based materials by polymerization of molecular Ru₂ complexes, featuring unprotected carboxylic acid substituents, with Cu(OAc)₂. The resulting crystalline heterobimetallic MOFs are solid-solutions of Ru₂ and Cu₂ sites housed within [M₃L₂] phases. The developed mechanochemical strategy is modular and allows for control of the primary coordination sphere of the Ru₂ sites. We anticipate the strategy will provide a rational approach to incorporation of kinetically inert ions in porous crystalline coordination networks, generating a class of atomically precise mixed-metal materials.