Metal Node Control of Brønsted Acidity in Heterobimetallic Titanium-Organic Frameworks.

Compared to indirect framework modification, synthetic control of cluster composition can be used to gain direct access to catalytic activities exclusive of specific metal combinations. We demonstrate this concept by testing the aminolysis of epoxides with a family of isostructural mesoporous frameworks featuring five combinations of homometallic and heterobimetallic metal-oxo trimers (Fe3, Ti3, TiFe2, TiCo2, and TiNi2). Only TiFe2 nodes display activities comparable to benchmark catalysts based on grafting of strong acids, which here originate from the combination of Lewis Ti4+ and Brønsted Fe3+-OH acid sites. The applicability of MUV-101(Fe) to the synthesis of ß-amino alcohols is demonstrated with a scope that also includes the gram scale synthesis of propranolol, a natural ß-blocker listed as an essential medicine by the World Health Organization, with excellent yield and selectivity.

Isoreticular Expansion and Linker-Enabled Control of Interpenetration in Titanium-Organic Frameworks.

Titanium-organic frameworks offer distinctive opportunities in the realm of metal-organic frameworks (MOFs) due to the integration of intrinsic photoactivity or redox versatility in porous architectures with ultrahigh stability. Unfortunately, the high polarizing power of Ti4+ cations makes them prone to hydrolysis, thus preventing the systematic design of these types of frameworks. We illustrate the use of heterobimetallic cluster Ti2Ca2 as a persistent building unit compatible with the isoreticular design of titanium frameworks. The MUV-12(X) and MUV-12(Y) series can be all synthesized as single crystals by using linkers of varying functionalization and size for the formation of the nets with tailorable porosity and degree of interpenetration. Following the generalization of this approach, we also gain rational control over interpenetration in these nets by designing linkers with varying degrees of steric hindrance to eliminate stacking interactions and access the highest gravimetric surface area reported for titanium(IV) MOFs (3000 m2 g-1).

A Crystalline 1D Dynamic Covalent Polymer.

The synthesis of crystalline one-dimensional polymers provides a fundamental understanding about the structure-property relationship in polymeric materials and allows the preparation of materials with enhanced thermal, mechanical, and conducting properties. However, the synthesis of crystalline one-dimensional polymers remains a challenge because polymers tend to adopt amorphous or semicrystalline phases. Herein, we report the synthesis of a crystalline one-dimensional polymer in solution by dynamic covalent chemistry. The structure of the polymer has been unambiguously confirmed by microcrystal electron diffraction that together with charge transport studies and theoretical calculations show how the π-stacked chains of the polymer generate optimal channels for charge transport.

Tetrazine Linkers as Plug-and-Play Tags for General Metal-Organic Framework Functionalization and C60 Conjugation.

The value of covalent post-synthetic modification in expanding the chemistry and pore versatility of reticular solids is well documented. Here we use mesoporous crystals of the metal-organic framework (MOF) UiO-68-TZDC to demonstrate the value of tetrazine connectors for all-purpose inverse electron-demand Diels-Alder ligation chemistry. Our results suggest a positive effect of tetrazine reticulation over its reactivity for quantitative one-step functionalization with a broad scope of alkene or alkyne dienophiles into pyridazine and dihydropyridazine frameworks. This permits generating multiple pore environments with diverse chemical functionalities and the expected accessible porosities, that is also extended to the synthesis of crystalline fulleretic materials by covalent conjugation of fullerene molecules.

Permanent Porosity in Hydroxamate Titanium-Organic Polyhedra.

Following the synthesis of hydroxamate titanium-organic frameworks, we now extend these siderophore-type linkers to the assembly of the first titanium-organic polyhedra displaying permanent porosity. Mixed-linker versions of this molecular cage (cMUV-11) are also used to demonstrate the effect of pore chemistry in accessing high surface areas of near 1200 m2·g-1.

Impact of Pore Size and Defects on the Selective Adsorption of Acetylene in Alkyne-Functionalized Nickel(II)-Pyrazolate-Based MOFs.

C2 H2 /CO2 separation is a highly challenging process as a consequence of their similar physicochemical properties. In this work we have explored, by static and dynamic gas sorption techniques and computational modelling, the suitability of a series of two isoreticular robust Ni(II)pyrazolate-based MOFs, bearing alkyne moieties on the ligand backbones, for C2 H2 /CO2 separation. The results are consistent with high adsorption capacity and selectivity of the essayed systems towards C2 H2 molecules. Furthermore, a post-synthetic treatment with KOH ethanolic solution gives rise to linker vacancy defects and incorporation of extraframework potassium ions. Creation of defects is responsible for increased adsorption capacity for both gases, however, strong interactions of the cluster basic sites and extraframework potassium cations with CO2 molecules are responsible for a lowering of C2 H2 over CO2 selectivity.

Selective Implantation of Diamines for Cooperative Catalysis in Isoreticular Heterometallic Titanium-Organic Frameworks.

We introduce the first example of isoreticular titanium-organic frameworks, MUV-10 and MUV-12, to show how the different affinity of hard Ti(IV) and soft Ca(II) metal sites can be used to direct selective grafting of amines. This enables the combination of Lewis acid titanium centers and available -NH2 sites in two sizeable pores for cooperative cycloaddition of CO2 to epoxides at room temperature and atmospheric pressure. The selective grafting of molecules to heterometallic clusters adds up to the pool of methodologies available for controlling the positioning and distribution of chemical functions in precise positions of the framework required for definitive control of pore chemistry.

Enantiodivergent Formation of C-P Bonds: Synthesis of P-Chiral Phosphines and Methylphosphonate Oligonucleotides.

Phosphorus Incorporation (PI, abbreviated Π) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from trans-limonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorus-Sulfur Incorporation reagents previously disclosed. Here, the adaptable phosphorus(V) scaffold enables sequential addition of carbon nucleophiles to produce a variety of enantiopure C-P building blocks. Addition of three carbon nucleophiles to Π, followed by stereospecific reduction, affords useful P-chiral phosphines; introduction instead of a single methyl group reveals the first stereospecific synthesis of methylphosphonate oligonucleotide precursors. While both Π enantiomers are available, only one isomer is required-the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.

Serine-Selective Bioconjugation.

This Communication reports the first general method for rapid, chemoselective, and modular functionalization of serine residues in native polypeptides, which uses a reagent platform based on the P(V) oxidation state. This redox-economical approach can be used to append nearly any kind of cargo onto serine, generating a stable, benign, and hydrophilic phosphorothioate linkage. The method tolerates all other known nucleophilic functional groups of naturally occurring proteinogenic amino acids. A variety of applications can be envisaged by this expansion of the toolbox of site-selective bioconjugation methods.

Heterometallic Titanium-Organic Frameworks by Metal-Induced Dynamic Topological Transformations.

Reticular chemistry has boosted the design of thousands of metal and covalent organic frameworks for unlimited chemical compositions, structures, and sizable porosities. The ability to generate porous materials at will on the basis of geometrical design concepts is responsible for the rapid growth of the field and the increasing number of applications derived. Despite their promising features, the synthesis of targeted homo- and heterometallic titanium-organic frameworks amenable to these principles is relentlessly limited by the high reactivity of this metal in solution that impedes the controlled assembly of titanium molecular clusters. We describe an unprecedented methodology for the synthesis of heterometallic titanium frameworks by metal-exchange reactions of MOF crystals at temperatures below those conventionally used in solvothermal synthesis. The combination of hard (titanium) and soft (calcium) metals in the heterometallic nodes of MUV-10(Ca) enables controlled metal exchange in soft positions for the generation of heterometallic secondary building units (SBUs) with variable nuclearity, controlled by the metal incorporated. The structural information encoded in the newly formed SBUs drives an MOF-to-MOF conversion into bipartite nets compatible with the connectivity of the organic linker originally present in the crystal. Our simulations show that this transformation has a thermodynamic origin and is controlled by the terminations of the (111) surfaces of the crystal. The reaction of MUV-10(Ca) with first-row transition metals permits the production of crystals of MUV-101(Fe,Co,Ni,Zn) and MUV-102(Cu), heterometallic titanium MOFs isostructural with archetypical solids such as MIL-100 and HKUST. In comparison to de novo synthesis, this metal-induced topological transformation provides control over the formation of hierarchical micro-/mesopore structures at different reaction times and enables the formation of heterometallic titanium MOFs not accessible under solvothermal conditions at high temperature, thus opening the door for the isolation of additional titanium heterometallic phases not linked exclusively to trimesate linkers.

Hydroxamate Titanium-Organic Frameworks and the Effect of Siderophore-Type Linkers over Their Photocatalytic Activity.

The chemistry of metal-organic frameworks (MOFs) relies on the controlled linking of organic molecules and inorganic secondary building units to assemble an unlimited number of reticular frameworks. However, the design of porous solids with chemical stability still remains limited to carboxylate or azolate groups. There is a timely opportunity to develop new synthetic platforms that make use of unexplored metal binding groups to produce metal-linker joints with hydrolytic stability. Living organisms use siderophores (iron carriers in Greek) to effectively assimilate iron in soluble form. These compounds make use of hard oxo donors as hydroxamate or catecholate groups to coordinate metal Lewis acids such as iron, aluminum, or titanium to form metal complexes very stable in water. Inspired by the chemistry of these microorganisms, we report the first hydroxamate MOF prepared by direct synthesis. MUV-11 (MUV = materials of Universidad de Valencia) is a crystalline, porous material (close to 800 m2·g-1) that combines photoactivity with good chemical stability in acid conditions. By using a high-throughput approach, we also demonstrate that this new chemistry is compatible with the formation of single-crystalline phases for multiple titanium salts, thus expanding the scope of accessible precursors. Titanium frameworks are regarded as promising materials for photocatalytic applications. Our photoelectrochemical and catalytic tests suggest important differences for MUV-11. Compared to other Ti-MOFs, changes in the photoelectrochemical and photocatalytic activity have been rationalized with computational modeling, revealing how the chemistry of siderophores can introduce changes to the electronic structure of the frontier orbitals, relevant to the photocatalytic activity of these solids.

A Radical Approach to Anionic Chemistry: Synthesis of Ketones, Alcohols, and Amines.

Historically accessed through two-electron, anionic chemistry, ketones, alcohols, and amines are of foundational importance to the practice of organic synthesis. After placing this work in proper historical context, this Article reports the development, full scope, and a mechanistic picture for a strikingly different way of forging such functional groups. Thus, carboxylic acids, once converted to redox-active esters (RAEs), can be utilized as formally nucleophilic coupling partners with other carboxylic derivatives (to produce ketones), imines (to produce benzylic amines), or aldehydes (to produce alcohols). The reactions are uniformly mild, operationally simple, and, in the case of ketone synthesis, broad in scope (including several applications to the simplification of synthetic problems and to parallel synthesis). Finally, an extensive mechanistic study of the ketone synthesis is performed to trace the elementary steps of the catalytic cycle and provide the end-user with a clear and understandable rationale for the selectivity, role of additives, and underlying driving forces involved.

Direct Visualization of Pyrrole Reactivity upon Confinement within a Cyclodextrin Metal-Organic Framework.

Metal-organic frameworks can be used as porous templates to exert control over polymerization reactions. Shown here are the possibilities offered by these crystalline, porous nanoreactors to capture highly-reactive intermediates for a better understanding of the mechanism of polymerization reactions. By using a cyclodextrin framework the polymerization of pyrrole is restricted, capturing the formation of terpyrrole cationic intermediates. Single-crystal X-ray diffraction is used to provide definite information on the supramolecular interactions that induce the formation and stabilization of a conductive array of cationic complexes.

Chemical Engineering of Photoactivity in Heterometallic Titanium-Organic Frameworks by Metal Doping.

We report a new family of titanium-organic frameworks that enlarges the limited number of crystalline, porous materials available for this metal. They are chemically robust and can be prepared as single crystals at multi-gram scale from multiple precursors. Their heterometallic structure enables engineering of their photoactivity by metal doping rather than by linker functionalization. Compared to other methodologies based on the post-synthetic metallation of MOFs, our approach is well-fitted for controlling the positioning of dopants at an atomic level to gain more precise control over the band-gap and electronic properties of the porous solid. Changes in the band-gap are also rationalized with computational modelling and experimentally confirmed by photocatalytic H2 production.

Synthesis of (±)-aureol by bioinspired rearrangements.

A bioinspired and sustainable procedure for the straightforward synthesis of (±)-aureol has been achieved in eight steps (14% overall yield) from epoxyfarnesol. The key steps are the titanocene(III)-catalyzed radical cascade cyclization of an epoxyfarnesol derivative and a biosynthetically inspired sequence of 1,2-hydride and methyl shifts.

Ti-catalyzed straightforward synthesis of exocyclic allenes.

Exocyclic allenes constitute useful building blocks in organic synthesis and have recently been identified as key intermediates in the synthesis of natural products. Here the first general method for the most straightforward synthesis of exocyclic allenes reported to date is presented. This method is based on the Barbier-type cyclization of propargyl halides catalyzed by titanium; a safe, abundant, and ecofriendly metal. The reaction proceeds under mild conditions compatible with different functional groups and provides good yields of five-, six-, and seven-membered carbocycles and nitrogen-containing heterocycles bearing an exocyclic allene group. Experimental evidence supporting the proposed reaction mechanism is also provided. Moreover, this procedure can be carried out in an enantioselective manner by using chiral titanocene(III) catalysts. The utility of this method has been proved in the synthesis of the natural alkaloid stemoamide.

Selective reduction of aromatic ketones in aqueous medium mediated by Ti(III)/Mn: a revised mechanism.

An experimental study on the role played by each of the reagents involved in the selective reduction of aromatic ketones in aqueous medium is reported. In this reaction, the reduction of aromatic ketones is mediated by Cp2TiCl. Moreover, the presence of Mn in the reaction medium is mandatory. To account for these findings, a substantially revised mechanism is proposed.

Tailoring the efficiency of porphyrin molecular frameworks for the electroactivation of molecular N2.

The combination of compositional versatility and topological diversity for the integration of electroactive species into high-porosity molecular architectures is perhaps one of the main appeals of metal-organic frameworks (MOFs) in the field of electrocatalysis. This premise has attracted much interest in recent years, and the results generated have also revealed one of the main limitations of molecular materials in this context: low stability under electrocatalytic conditions. Using zirconium MOFs as a starting point, in this work, we use this stability as a variable to discriminate between the most suitable electrocatalytic reaction and specific topologies within this family. Our results revealed that the PCN-224 family is particularly suitable for the electroreduction of molecular nitrogen for the formation of ammonia with faradaic efficiencies above 30% in the presence of Ni2+ sites, an activity that improves most of the catalysts described. We also introduce the fluorination of porphyrin at the meso position as a good alternative to improve both the activity and stability of this material under electrocatalytic conditions.

Chemical complexity for targeted function in heterometallic titanium-organic frameworks.

Research on metal-organic frameworks is shifting from the principles that control the assembly, structure, and porosity of these reticular solids, already established, into more sophisticated concepts that embrace chemical complexity as a tool for encoding their function or accessing new properties by exploiting the combination of different components (organic and inorganic) into these networks. The possibility of combining multiple linkers into a given network for multivariate solids with tunable properties dictated by the nature and distribution of the organic connectors across the solid has been well demonstrated. However, the combination of different metals remains still comparatively underexplored due to the difficulties in controlling the nucleation of heterometallic metal-oxo clusters during the assembly of the framework or the post-synthetic incorporation of metals with distinct chemistry. This possibility is even more challenging for titanium-organic frameworks due to the additional difficulties intrinsic to controlling the chemistry of titanium in solution. In this perspective article we provide an overview of the synthesis and advanced characterization of mixed-metal frameworks and emphasize the particularities of those based in titanium with particular focus on the use of additional metals to modify their function by controlling their reactivity in the solid state, tailoring their electronic structure and photocatalytic activity, enabling synergistic catalysis, directing the grafting of small molecules or even unlocking the formation of mixed oxides with stoichiometries not accessible to conventional routes.

Hydrogen atom donors: recent developments.

This review highlights recent developments in the field of hydrogen atom transfer (HAT) reagents that circumvent the disadvantages of classical group 14 reagents, such as Bu3SnH. Special emphasis is laid on the lowering of bond dissociation energies (BDEs) of molecules that could, as yet, not be used as HAT reagents and on the use of organometallic HAT reagents.