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The synthesis of amides from amines and carboxylic acids is the most widely carried out reaction in medicinal chemistry. Yet, most amide couplings are still conducted using stoichiometric reagents, leading to significant waste; few synthetic catalysts for this transformation have been adopted industrially due to their limited scope and/or poor recyclability. The majority of catalytic approaches focus on a single activation mode, such as enhancing the electrophilicity of the carboxylic acid partner using a Lewis acid. In contrast, nature effortlessly forges and breaks amide bonds using precise arrays of Lewis/Brønsted acidic and basic functional groups. Drawing inspiration from these systems, herein we report a simple defect engineering strategy to colocalize Lewis acidic Zr sites with other catalytically active species within porous metal-organic frameworks (MOFs). Specifically, the combination of pyridine N -oxide and Zr open metal sites within the defective framework MOF-808-py-Nox produces a heterogeneous catalyst that facilitates amide bond formation with broad functional group compatibility from amines and carboxylic acids, esters, or primary amides. Extensive density functional theory (DFT) calculations using cluster models support that the formation of a hydrogen-bonding network at the defect sites facilitates amide bond formation in this material. MOF-808-py-Nox can be recycled at least five times without losing significant crystallinity, porosity, or catalytic activity and can be employed in continuous flow. This defect engineering strategy can be potentially generalized to produce libraries of catalytically active MOFs with different combinations of colocalized functional groups.

Hydrogen sulfide (H 2 S) is an endogenously produced gasotransmitter involved in many physiological processes that are integral to proper cellular functioning. Due to its profound anti-inflammatory and antioxidant properties, H 2 S plays important roles in preventing inflammatory skin disorders and improving wound healing. Transdermal H 2 S delivery is a therapeutically viable option for the management of such disorders. However, current small-molecule H 2 S donors are not optimally suited for transdermal delivery and typically generate electrophilic byproducts that may lead to undesired toxicity. Here, we demonstrate that H 2 S release from metal-organic frameworks (MOFs) bearing coordinatively unsaturated metal centers is a promising alternative for controlled transdermal delivery of H 2 S. Gas sorption measurements and powder X-ray diffraction (PXRD) studies of 11 MOFs support that the Mg-based framework Mg 2 (dobdc) (dobdc 4- = 2,5-dioxidobenzene-1,4-dicarboxylate) is uniquely well-suited for transdermal H 2 S delivery due to its strong yet reversible binding of H 2 S, high capacity (14.7 mmol/g at 1 bar and 25 °C), and lack of toxicity. In addition, Rietveld refinement of synchrotron PXRD data from H 2 S-dosed Mg 2 (dobdc) supports that the high H 2 S capacity of this framework arises due to the presence of three distinct binding sites. Last, we demonstrate that transdermal delivery of H 2 S from Mg 2 (dobdc) is sustained over a 24 h period through porcine skin. Not only is this significantly longer than sodium sulfide but this represents the first example of controlled transdermal delivery of pure H 2 S gas. Overall, H 2 S-loaded Mg 2 (dobdc) is an easily accessible, solid-state source of H 2 S, enabling safe storage and transdermal delivery of this therapeutically relevant gas.

The selective halogenation of complex (hetero)aromatic systems is a critical yet challenging transformation that is relevant to medicinal chemistry, agriculture, and biomedical imaging. However, current methods are limited by toxic reagents, expensive homogeneous second- and third-row transition metal catalysts, or poor substrate tolerance. Herein, we demonstrate that porous metal-organic frameworks (MOFs) containing terminal Co(III) halide sites represent a rare and general class of heterogeneous catalysts for the controlled installation of chlorine and fluorine centers into electron-deficient (hetero)aryl bromides using simple metal halide salts. Mechanistic studies support that these halogen exchange (halex) reactions proceed via redox-neutral nucleophilic aromatic substitution (S N Ar) at the Co(III) sites. The MOF-based halex catalysts are recyclable, enable green halogenation with minimal waste generation, and facilitate halex in a continuous flow. Our findings represent the first example of S N Ar catalysis using MOFs, expanding the lexicon of synthetic transformations enabled by these materials.

Diamine-appended Mg 2 (dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) metal-organic frameworks are promising candidates for carbon capture that exhibit exceptional selectivities and high capacities for CO 2 . To date, CO 2 uptake in these materials has been shown to occur predominantly via a chemisorption mechanism involving CO 2 insertion at the amine-appended metal sites, a mechanism that limits the capacity of the material to ∼1 equiv of CO 2 per diamine. Herein, we report a new framework, pip2-Mg 2 (dobpdc) (pip2 = 1-(2-aminoethyl)piperidine), that exhibits two-step CO 2 uptake and achieves an unusually high CO 2 capacity approaching 1.5 CO 2 per diamine at saturation. Analysis of variable-pressure CO 2 uptake in the material using solid-state nuclear magnetic resonance (NMR) spectroscopy and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) reveals that pip2-Mg 2 (dobpdc) captures CO 2 via an unprecedented mechanism involving the initial insertion of CO 2 to form ammonium carbamate chains at half of the sites in the material, followed by tandem cooperative chemisorption and physisorption. Powder X-ray diffraction analysis, supported by van der Waals-corrected density functional theory, reveals that physisorbed CO 2 occupies a pocket formed by adjacent ammonium carbamate chains and the linker. Based on breakthrough and extended cycling experiments, pip2-Mg 2 (dobpdc) exhibits exceptional performance for CO 2 capture under conditions relevant to the separation of CO 2 from landfill gas. More broadly, these results highlight new opportunities for the fundamental design of diamine-Mg 2 (dobpdc) materials with even higher capacities than those predicted based on CO 2 chemisorption alone.

Diamine-appended Mg 2 (dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) metal-organic frameworks have emerged as promising candidates for carbon capture owing to their exceptional CO 2 selectivities, high separation capacities, and step-shaped adsorption profiles, which arise from a unique cooperative adsorption mechanism resulting in the formation of ammonium carbamate chains. Materials appended with primary , secondary -diamines featuring bulky substituents, in particular, exhibit excellent stabilities and CO 2 adsorption properties. However, these frameworks display double-step adsorption behavior arising from steric repulsion between ammonium carbamates, which ultimately results in increased regeneration energies. Herein, we report frameworks of the type diamine-Mg 2 (olz) (olz 4- = ( E )-5,5'-(diazene-1,2-diyl)bis(2-oxidobenzoate)) that feature diverse diamines with bulky substituents and display desirable single-step CO 2 adsorption across a wide range of pressures and temperatures. Analysis of CO 2 adsorption data reveals that the basicity of the pore-dwelling amine─in addition to its steric bulk─is an important factor influencing adsorption step pressure; furthermore, the amine steric bulk is found to be inversely correlated with the degree of cooperativity in CO 2 uptake. One material, ee-2-Mg 2 (olz) (ee-2 = N , N -diethylethylenediamine), adsorbs >90% of the CO 2 from a simulated coal flue stream and exhibits exceptional thermal and oxidative stability over the course of extensive adsorption/desorption cycling, placing it among top-performing adsorbents to date for CO 2 capture from a coal flue gas. Spectroscopic characterization and van der Waals-corrected density functional theory calculations indicate that diamine-Mg 2 (olz) materials capture CO 2 via the formation of ammonium carbamate chains. These results point more broadly to the opportunity for fundamentally advancing materials in this class through judicious design.

Metal-organic frameworks (MOFs) are crystalline, porous solids constructed from organic linkers and inorganic nodes that are promising for applications in chemical separations, gas storage, and catalysis, among many others. However, a major roadblock to the widespread implementation of MOFs, including highly tunable and hydrolytically stable Zr- and Hf-based frameworks, is their benchtop-scalable synthesis, as MOFs are typically prepared under highly dilute (≤0.01 M) solvothermal conditions. This necessitates the use of liters of organic solvent to prepare only a few grams of MOF. Herein, we demonstrate that Zr- and Hf-based frameworks (eight examples) can self-assemble at much higher reaction concentrations than are typically utilized, up to 1.00 M in many cases. Combining stoichiometric amounts of Zr or Hf precursors with organic linkers at high concentrations yields highly crystalline and porous MOFs, as confirmed by powder X-ray diffraction (PXRD) and 77 K N 2 surface area measurements. Furthermore, the use of well-defined pivalate-capped cluster precursors avoids the formation of ordered defects and impurities that arise from standard metal chloride salts. These clusters also introduce pivalate defects that increase the exterior hydrophobicity of several MOFs, as confirmed by water contact angle measurements. Overall, our findings challenge the standard assumption that MOFs must be prepared under highly dilute solvothermal conditions for optimal results, paving the way for their scalable and user-friendly synthesis in the laboratory.

The crystal packing of organic chromophores has a profound impact on their photophysical properties. Molecular crystal engineering is generally incapable of producing precisely spaced arrays of molecules for use in photovoltaics, light-emitting diodes, and sensors. A promising alternative strategy is the incorporation of chromophores into crystalline metal-organic frameworks (MOFs), leading to matrix coordination-induced emission (MCIE) upon confinement. However, it remains unclear how the precise arrangement of chromophores and defects dictates photophysical properties in these systems, limiting the rational design of well-defined photoluminescent materials. Herein, we report new, robust Zr-based MOFs constructed from the linker tetrakis(4-carboxyphenyl)ethylene (TCPE 4- ) that exhibit an unexpected structural transition in combination with a prominent shift from green to blue photoluminescence (PL) as a function of the amount of acid modulator (benzoic, formic, or acetic acid) used during synthesis. Time-resolved PL (TRPL) measurements provide full spectral information and reveal that the observed hypsochromic shift arises due to a higher concentration of linker substitution defects at higher modulator concentrations, leading to broader excitation transfer-induced spectral diffusion. Spectral diffusion of this type has not been reported in a MOF to date, and its observation provides structural information that is otherwise unobtainable using traditional crystallographic techniques. Our findings suggest that defects have a profound impact on the photophysical properties of MOFs and that their presence can be readily tuned to modify energy transfer processes within these materials.

Carbon capture at fossil fuel-fired power plants is a critical strategy to mitigate anthropogenic contributions to global warming, but widespread deployment of this technology is hindered by a lack of energy-efficient materials that can be optimized for CO 2 capture from a specific flue gas. As a result of their tunable, step-shaped CO 2 adsorption profiles, diamine-functionalized metal-organic frameworks (MOFs) of the form diamine-Mg 2 (dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) are among the most promising materials for carbon capture applications. Here, we present a detailed investigation of dmen-Mg 2 (dobpdc) (dmen = 1,2-diamino-2-methylpropane), one of only two MOFs with an adsorption step near the optimal pressure for CO 2 capture from coal flue gas. While prior characterization suggested that this material only adsorbs CO 2 to half capacity (0.5 CO 2 per diamine) at 1 bar, we show that the half-capacity state is actually a metastable intermediate. Under appropriate conditions, the MOF adsorbs CO 2 to full capacity, but conversion from the half-capacity structure happens on a very slow time scale, rendering it inaccessible in traditional adsorption measurements. Data from solid-state magic angle spinning nuclear magnetic resonance spectroscopy, coupled with van der Waals-corrected density functional theory, indicate that ammonium carbamate chains formed at half capacity and full capacity adopt opposing configurations, and the need to convert between these states likely dictates the sluggish post-half-capacity uptake. By use of the more symmetric parent framework Mg 2 (pc-dobpdc) (pc-dobpdc 4- = 3,3'-dioxidobiphenyl-4,4'-dicarboxylate), the metastable trap can be avoided and the full CO 2 capacity of dmen-Mg 2 (pc-dobpdc) accessed under conditions relevant for carbon capture from coal-fired power plants.

Fluoroarenes are widely used in medicinal, agricultural, and materials chemistry, and yet their production remains a critical challenge in organic synthesis. Indeed, the nearly identical physical properties of these vital building blocks hinders their purification by traditional methods, such as flash chromatography or distillation. As a result, the Balz-Schiemann reaction is currently employed to prepare fluoroarenes instead of more atom-economical C-H fluorination reactions, which produce inseparable mixtures of regioisomers. Herein, we propose an alternative solution to this problem: the purification of mixtures of fluoroarenes using metal-organic frameworks (MOFs). Specifically, we demonstrate that controlling the interaction of fluoroarenes with adjacent coordinatively unsaturated Mg 2+ centers within a MOF enables the separation of fluoroarene mixtures with unparalleled selectivities. Liquid-phase multicomponent equilibrium adsorption data and breakthrough measurements coupled with van der Waals-corrected density functional theory calculations reveal that the materials Mg 2 (dobdc) (dobdc 4- = 2,5-dioxidobenzene-1,4-dicarboxylate) and Mg 2 ( m -dobdc) ( m -dobdc 4- = 2,4-dioxidobenzene-1,5-dicarboxylate) are capable of separating the difluorobenzene isomers from one another. Additionally, these frameworks facilitate the separations of fluoroanisoles, fluorotoluenes, and fluorochlorobenzenes. In addition to enabling currently unfeasible separations for the production of fluoroarenes, our results suggest that carefully controlling the interaction of isomers with not one but two strong binding sites within a MOF provides a general strategy for achieving challenging liquid-phase separations.

Supported by increasingly available reserves, natural gas is achieving greater adoption as a cleaner-burning alternative to coal in the power sector. As a result, carbon capture and sequestration from natural gas-fired power plants is an attractive strategy to mitigate global anthropogenic CO 2 emissions. However, the separation of CO 2 from other components in the flue streams of gas-fired power plants is particularly challenging due to the low CO 2 partial pressure (∼40 mbar), which necessitates that candidate separation materials bind CO 2 strongly at low partial pressures (≤4 mbar) to capture ≥90% of the emitted CO 2 . High partial pressures of O 2 (120 mbar) and water (80 mbar) in these flue streams have also presented significant barriers to the deployment of new technologies for CO 2 capture from gas-fired power plants. Here, we demonstrate that functionalization of the metal-organic framework Mg 2 (dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) with the cyclic diamine 2-(aminomethyl)piperidine (2-ampd) produces an adsorbent that is capable of ≥90% CO 2 capture from a humid natural gas flue emission stream, as confirmed by breakthrough measurements. This material captures CO 2 by a cooperative mechanism that enables access to a large CO 2 cycling capacity with a small temperature swing (2.4 mmol CO 2 /g with Δ T = 100 °C). Significantly, multicomponent adsorption experiments, infrared spectroscopy, magic angle spinning solid-state NMR spectroscopy, and van der Waals-corrected density functional theory studies suggest that water enhances CO 2 capture in 2-ampd-Mg 2 (dobpdc) through hydrogen-bonding interactions with the carbamate groups of the ammonium carbamate chains formed upon CO 2 adsorption, thereby increasing the thermodynamic driving force for CO 2 binding. In light of the exceptional thermal and oxidative stability of 2-ampd-Mg 2 (dobpdc), its high CO 2 adsorption capacity, and its high CO 2 capture rate from a simulated natural gas flue emission stream, this material is one of the most promising adsorbents to date for this important separation.

The widespread deployment of carbon capture and sequestration as a climate change mitigation strategy could be facilitated by the development of more energy-efficient adsorbents. Diamine-appended metal-organic frameworks of the type diamine-M 2 (dobpdc) (M = Mg, Mn, Fe, Co, Ni, Zn; dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) have shown promise for carbon-capture applications, although questions remain regarding the molecular mechanisms of CO 2 uptake in these materials. Here we leverage the crystallinity and tunability of this class of frameworks to perform a comprehensive study of CO 2 chemisorption. Using multinuclear nuclear magnetic resonance (NMR) spectroscopy experiments and van-der-Waals-corrected density functional theory (DFT) calculations for 13 diamine-M 2 (dobpdc) variants, we demonstrate that the canonical CO 2 chemisorption products, ammonium carbamate chains and carbamic acid pairs, can be readily distinguished and that ammonium carbamate chain formation dominates for diamine-Mg 2 (dobpdc) materials. In addition, we elucidate a new chemisorption mechanism in the material dmpn-Mg 2 (dobpdc) (dmpn = 2,2-dimethyl-1,3-diaminopropane), which involves the formation of a 1:1 mixture of ammonium carbamate and carbamic acid and accounts for the unusual adsorption properties of this material. Finally, we show that the presence of water plays an important role in directing the mechanisms for CO 2 uptake in diamine-M 2 (dobpdc) materials. Overall, our combined NMR and DFT approach enables a thorough depiction and understanding of CO 2 adsorption within diamine-M 2 (dobpdc) compounds, which may aid similar studies in other amine-functionalized adsorbents in the future.

Purification of the C 8 alkylaromatics o-xylene, m-xylene, p-xylene, and ethylbenzene remains among the most challenging industrial separations, due to the similar shapes, boiling points, and polarities of these molecules. Herein, we report the evaluation of the metal-organic frameworks Co 2 (dobdc) (dobdc 4- = 2,5-dioxido-1,4-benzenedicarboxylate) and Co 2 ( m-dobdc) ( m-dobdc 4- = 4,6-dioxido-1,3-benzenedicarboxylate) for the separation of xylene isomers using single-component adsorption isotherms and multicomponent breakthrough measurements. Remarkably, Co 2 (dobdc) distinguishes among all four molecules, with binding affinities that follow the trend o-xylene > ethylbenzene > m-xylene > p-xylene. Multicomponent liquid-phase adsorption measurements further demonstrate that Co 2 (dobdc) maintains this selectivity over a wide range of concentrations. Structural characterization by single-crystal X-ray diffraction reveals that both frameworks facilitate the separation through the extent of interaction between each C 8 guest molecule with two adjacent cobalt(II) centers, as well as the ability of each isomer to pack within the framework pores. Moreover, counter to the presumed rigidity of the M 2 (dobdc) structure, Co 2 (dobdc) exhibits an unexpected structural distortion in the presence of either o-xylene or ethylbenzene that enables the accommodation of additional guest molecules.

Metal-organic frameworks are promising materials for energy-efficient gas separations, but little is known about the diffusion of adsorbates in materials featuring one-dimensional porosity at the nanoscale. An understanding of the interplay between framework structure and gas diffusion is crucial for the practical application of these materials as adsorbents or in mixed-matrix membranes, since the rate of gas diffusion within the adsorbent pores impacts the required size (and therefore cost) of the adsorbent column or membrane. Here, we investigate the diffusion of CO 2 within the pores of Zn 2 (dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) using pulsed field gradient (PFG) nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations. The residual chemical shift anisotropy for pore-confined CO 2 allows PFG NMR measurements of self-diffusion in different crystallographic directions, and our analysis of the entire NMR line shape as a function of the applied field gradient provides a precise determination of the self-diffusion coefficients. In addition to observing CO 2 diffusion through the channels parallel to the crystallographic c axis (self-diffusion coefficient D ∥ = (5.8 ± 0.1) × 10 -9 m 2 s -1 at a pressure of 625 mbar CO 2 ), we unexpectedly find that CO 2 is also able to diffuse between the hexagonal channels in the crystallographic ab plane (D ⊥ = (1.9 ± 0.2) × 10 -10 m 2 s -1 ), despite the walls of these channels appearing impermeable by single-crystal X-ray crystallography and flexible lattice MD simulations. Observation of such unexpected diffusion in the ab plane suggests the presence of defects that enable effective multidimensional CO 2 transport in a metal-organic framework with nominally one-dimensional porosity.

Chiral metal-organic frameworks have attracted interest for enantioselective separations and catalysis because of their high crystallinity and pores with tunable shapes, sizes, and chemical environments. Chiral frameworks of the type M 2 (dobpdc) (M = Mg, Mn, Fe, Co, Ni, Zn; dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) seem particularly promising for potential applications because of their excellent stability, high internal surface areas, and strongly polarizing open metal coordination sites within the channels, but to date these materials have been isolated only in racemic form. Here, we demonstrate that when appended with the chiral diamine trans-1,2-diaminocyclohexane (dach), Mg 2 (dobpdc) adsorbs carbon dioxide cooperatively to form ammonium carbamate chains, and the thermodynamics of CO 2 capture are strongly influenced by enantioselective interactions within the chiral pores of the framework. We further show that it is possible to access both enantiomers of Mg 2 (dobpdc) with high enantiopurity (≥90%) via framework synthesis in the presence of varying quantities of d-panthenol, an inexpensive chiral induction agent. Investigation of dach-M 2 (dobpdc) samples following CO 2 adsorption-using single-crystal and powder X-ray diffraction, solid-state nuclear magnetic resonance spectroscopy, and density functional theory calculations-revealed that the ammonium carbamate chains interact extensively with each other and with the chiral M 2 (dobpdc) pore walls. Subtle differences in the non-covalent interactions accessible in each diastereomeric phase dramatically impact the thermodynamics of CO 2 adsorption.

A new diamine-functionalized metal-organic framework comprised of 2,2-dimethyl-1,3-diaminopropane (dmpn) appended to the Mg 2+ sites lining the channels of Mg 2 (dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) is characterized for the removal of CO 2 from the flue gas emissions of coal-fired power plants. Unique to members of this promising class of adsorbents, dmpn-Mg 2 (dobpdc) displays facile step-shaped adsorption of CO 2 from coal flue gas at 40 °C and near complete CO 2 desorption upon heating to 100 °C, enabling a high CO 2 working capacity (2.42 mmol/g, 9.1 wt %) with a modest 60 °C temperature swing. Evaluation of the thermodynamic parameters of adsorption for dmpn-Mg 2 (dobpdc) suggests that the narrow temperature swing of its CO 2 adsorption steps is due to the high magnitude of its differential enthalpy of adsorption (Δh ads = -73 ± 1 kJ/mol), with a larger than expected entropic penalty for CO 2 adsorption (Δs ads = -204 ± 4 J/mol·K) positioning the step in the optimal range for carbon capture from coal flue gas. In addition, thermogravimetric analysis and breakthrough experiments indicate that, in contrast to many adsorbents, dmpn-Mg 2 (dobpdc) captures CO 2 effectively in the presence of water and can be subjected to 1000 humid adsorption/desorption cycles with minimal degradation. Solid-state 13 C NMR spectra and single-crystal X-ray diffraction structures of the Zn analogue reveal that this material adsorbs CO 2 via formation of both ammonium carbamates and carbamic acid pairs, the latter of which are crystallographically verified for the first time in a porous material. Taken together, these properties render dmpn-Mg 2 (dobpdc) one of the most promising adsorbents for carbon capture applications.

In the transition to a clean-energy future, CO 2 separations will play a critical role in mitigating current greenhouse gas emissions and facilitating conversion to cleaner-burning and renewable fuels. New materials with high selectivities for CO 2 adsorption, large CO 2 removal capacities, and low regeneration energies are needed to achieve these separations efficiently at scale. Here, we present a detailed investigation of nine diamine-appended variants of the metal-organic framework Mg 2 (dobpdc) (dobpdc 4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) that feature step-shaped CO 2 adsorption isotherms resulting from cooperative and reversible insertion of CO 2 into metal-amine bonds to form ammonium carbamate chains. Small modifications to the diamine structure are found to shift the threshold pressure for cooperative CO 2 adsorption by over 4 orders of magnitude at a given temperature, and the observed trends are rationalized on the basis of crystal structures of the isostructural zinc frameworks obtained from in situ single-crystal X-ray diffraction experiments. The structure-activity relationships derived from these results can be leveraged to tailor adsorbents to the conditions of a given CO 2 separation process. The unparalleled versatility of these materials, coupled with their high CO 2 capacities and low projected energy costs, highlights their potential as next-generation adsorbents for a wide array of CO 2 separations.

Metal-organic frameworks are a new class of heterogeneous catalysts in which molecular-level control over both the immediate and long-range chemical environment surrounding a catalytic center can be readily achieved. Here, the oxidation of cyclohexane to cyclohexanol and cyclohexanone is used as a model reaction to investigate the effect of a hydrophobic pore environment on product selectivity and catalyst stability in a series of iron-based frameworks. Specifically, expanded analogues of Fe 2 (dobdc) (dobdc 4- = 2,5-dioxido-1,4-benzenedicarboxylate) were synthesized and evaluated, including the biphenyl derivative Fe 2 (dobpdc) (H 4 dobpdc = 4,4'-dihydroxy-[1,1'-biphenyl]-3,3'-dicarboxylic acid), the terphenyl derivative Fe 2 (dotpdc) (H 4 dotpdc = 4,4″-dihydroxy-[1,1':4',1″-terphenyl]-3,3″-dicarboxylic acid), and three modified terphenyl derivatives in which the central ring is replaced with tetrafluoro-, tetramethyl-, or di-tert-butylaryl groups. Within these five materials, a remarkable 3-fold enhancement of the alcohol:ketone (A:K) ratio and an order of magnitude increase in turnover number are achieved by simply altering the framework pore diameter and installing nonpolar functional groups near the iron site. Mössbauer spectroscopy, kinetic isotope effect, and gas adsorption measurements reveal that variations in the A:K selectivities arise from differences in the cyclohexane adsorption enthalpies of these frameworks, which become more favorable as the number of hydrophobic residues and thus van der Waals interactions increase.

A new radiosynthetic protocol for the preparation of [(11)C]aryl nitriles has been developed. This process is based on the direct reaction of in situ prepared L·Pd(Ar)X complexes (L = biaryl phosphine) with [(11)C]HCN. The strategy is operationally simple, exhibits a remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity compared to previously reported systems. With this procedure, a variety of [(11)C]nitrile-containing pharmaceuticals were prepared with high radiochemical efficiency.

Isotopic labeling has been used to determine that a portion of the desired product in the Pd-catalyzed fluorination of electron-rich, non-ortho-substituted aryl triflates results from direct C-F cross-coupling. In some cases, formation of a Pd-aryne intermediate is responsible for producing undesired regioisomers. The generation of the Pd-aryne intermediate occurs primarily via ortho-deprotonation of a L·Pd(Ar)OTf (L = biaryl monophosphine) species by CsF and thus competes directly with the transmetalation step of the catalytic cycle. Deuterium labeling studies were conducted with a variety of aryl triflates.

On the basis of mechanism-driven reaction design, a Pd-catalyzed nucleophilic fluorination of aryl bromides and iodides has been developed. The method exhibits a broad substrate scope, especially with respect to nitrogen-containing heteroaryl bromides, and proceeds with minimal formation of the corresponding reduction products. A facilitated ligand modification process was shown to be critical to the success of the reaction.

A series of monoligated L·Pd(II)(Ar)X complexes (L = dialkyl biaryl phosphine) have been prepared and studied in an effort to better understand an unusual dearomative rearrangement previously documented in these systems. Experimental and theoretical evidence suggest a concerted process involving the unprecedented Pd(II)-mediated insertion of an aryl group into an unactivated arene.

A mechanistic investigation of the Pd-catalyzed conversion of aryl triflates to fluorides is presented. Studies reveal that C-F reductive elimination from a LPd(II)(aryl)F complex (L = t-BuBrettPhos or RockPhos) does not occur when the aryl group is electron rich. Evidence is presented that a modified phosphine, generated in situ, serves as the actual supporting ligand during catalysis with such substrates. A preliminary study of the reactivity of a LPd(II)(aryl)F complex based on this modified ligand is reported.