Transition Metal Catalysis Controlled by Hydrogen Bonding in the Second Coordination Sphere.

Transition metal catalysis is of utmost importance for the development of sustainable processes in academia and industry. The activity and selectivity of metal complexes are typically the result of the interplay between ligand and metal properties. As the ligand can be chemically altered, a large research focus has been on ligand development. More recently, it has been recognized that further control over activity and selectivity can be achieved by using the "second coordination sphere", which can be seen as the region beyond the direct coordination sphere of the metal center. Hydrogen bonds appear to be very useful interactions in this context as they typically have sufficient strength and directionality to exert control of the second coordination sphere, yet hydrogen bonds are typically very dynamic, allowing fast turnover. In this review we have highlighted several key features of hydrogen bonding interactions and have summarized the use of hydrogen bonding to program the second coordination sphere. Such control can be achieved by bridging two ligands that are coordinated to a metal center to effectively lead to supramolecular bidentate ligands. In addition, hydrogen bonding can be used to preorganize a substrate that is coordinated to the metal center. Both strategies lead to catalysts with superior properties in a variety of metal catalyzed transformations, including (asymmetric) hydrogenation, hydroformylation, C-H activation, oxidation, radical-type transformations, and photochemical reactions.

Gold Catalysis in (Supra)Molecular Cages to Control Reactivity and Selectivity.

Gold catalysis has experienced a tremendous development over the past decades, and is nowadays widely used in organic synthesis to perform chemical transformations of π-bond-containing molecules. Catalyst development has been based mostly on ligand development and counter-ion strategies. More recently, the encapsulation of gold catalysts in (supra)molecular cages was explored as a new way to control selectivity and reactivity of gold catalysts. In this review, we describe the cages that have been employed as hosts for gold complexes, along with their impact on the catalytic performance. Covalent and supramolecular approaches to encapsulate single metal complexes will be described and the impact on the catalytic performance will be discussed. Also, recent strategies to pre-organize multiple metal centers will be discussed.

Self-assembled M12L24 nanospheres as a reaction vessel to facilitate a dinuclear Cu(i) catalyzed cyclization reaction.

The application of large M12L24 nanospheres allows the pre-concentration of catalysts to reach high local concentrations, facilitating reactions that proceed through dinuclear mechanisms. The mechanism of the copper(i)-catalyzed cyclization of 4-pentynoic acid has been elucidated by means of a detailed mechanistic study. The kinetics of the reaction show a higher order in copper, indicating the formation of a bis-Cu intermediate as the key rate determining step of the reaction. This intermediate was further identified during catalysis by CIS-HRMS analysis of the reaction mixture. Based on the mechanistic findings, an M12L24 nanosphere was applied that can bind up to 12 copper catalysts by hydrogen bonding. This pre-organization of copper catalysts in the nanosphere results in a high local concentration of copper leading to higher reaction rates and turnover numbers as the dinuclear pathway is favored.

Modulation of catalyst enantioselectivity through reversible assembly of supramolecular helices.

A multi-configurable catalyst, for which the degree of enantioinduction in successive reactions is varied between 6% ee and 52% ee, is achieved by supporting copper centres at the periphery of supramolecular helices. Precise characterization of the co-assemblies corroborates the relation between helix length and catalyst selectivity.

Ligand Template Strategies for Catalyst Encapsulation.

Binding of molecules in molecular cages based on self-assembled concave building blocks has been of great interest to scientists for decades. The binding of static molecular fragments inside cage-like molecular structures is generally based on complementarity of host and guest in terms of shape and interactions. The encapsulation of homogeneous catalysts in molecular cages is of interest as activity, selectivity, and stability can be controlled by the cage as second coordination sphere, reminiscent of how enzymes control chemical reactivity. Homogeneous catalysts, however, are not static guest molecules as catalysts change in shape, charge, and polarity during the catalytic cycle, representing the challenges involved in cage controlled catalysis. To address these issues, we developed a new strategy that we coined the "ligand template approach for catalyst encapsulation". This strategy relies on ligand building blocks that contain multiple orthogonal binding sites: the central ligand (mostly phosphorus) is bound to the transition metal required for catalysis, while other binding sites are used to construct a cage structure around the transition metal atom through self-assembly. By design, the catalyst is inside the capsule during the catalytic cycle, as the central ligand is coordinated to the catalyst. As the approach is based on a self-assembly process of building blocks, the catalyst properties can be easily modulated by modification of building blocks involved. In this Account, we elaborate on template ligand strategies for single catalyst encapsulation, based on divergent ligand templates and the extension to nanospheres with multiple metal complexes, which are formed by assembly of convergent ligand templates. Using the mononuclear approach, a variety of encapsulated catalysts can be generated, which have led to highly (enantio)selective hydroformylation reactions for encapsulated rhodium atoms. Besides the successes of encapsulated rhodium catalysts in hydroformylation, mononuclear ligand template capsules have been applied in asymmetric hydrogenation, the Heck reaction, copolymerization, gold catalyzed cyclization reactions, and hydrosilylation reactions. By changing the capsule building blocks the electronic and steric properties around the transition metal atom have successfully been modified, which translates to changes in catalyst properties. Using the convergent ligand templates, nanospheres have been generated with up to 24 complexes inside the sphere, leading to very high local concentrations of the transition metal. The effect of local concentrations was explored in gold catalyzed cyclization reactions and ruthenium catalyzed water oxidation, and for both reactions, spectacular reaction rate enhancements have been observed. This Account shows that the template ligand approach to provide catalyst in well-defined specific environments is very versatile and leads to catalyst properties that are not achievable with traditional approaches.

Real-Time Control of the Enantioselectivity of a Supramolecular Catalyst Allows Selecting the Configuration of Consecutively Formed Stereogenic Centers.

The enantiomeric state of a supramolecular copper catalyst can be switched in situ in ca. five seconds. The dynamic property of the catalyst is provided by the non-covalent nature of the helical assemblies supporting the copper centers. These assemblies are formed by mixing an achiral benzene-1,3,5-tricarboxamide (BTA) phosphine ligand (for copper coordination) and both enantiomers of a chiral phosphine-free BTA co-monomer (for chirality amplification). The enantioselectivity of the hydrosilylation reaction is fixed by the BTA enantiomer in excess, which can be altered by simple BTA addition. As a result of the complete and fast stereochemical switch, any combination of the enantiomers was obtained during the conversion of a mixture of two substrates.

Tuning the structure of 1,3,5-benzene tricarboxamide self-assemblies through stereochemistry.

A heterochiral 1,3,5-benzene tricarboxamide (BTA) monomer, derived from valine dodecyl ester, forms long rods in cyclohexane whilst its homochiral analogue assembles into dimers only at the same concentration. This highly original assembly behaviour is related to the destabilization of the dimeric structure containing the two heterochiral monomers as corroborated by a combined experimental and computational study.

Tuning the nature and stability of self-assemblies formed by ester benzene 1,3,5-tricarboxamides: the crucial role played by the substituents.

As the benzene 1,3,5-tricarboxamide (BTA) moiety is commonly used as the central assembling unit for the construction of functionalized supramolecular architectures, strategies to tailor the nature and stability of BTA assemblies are needed. The assembly properties of a library of structurally simple BTAs derived from amino dodecyl esters (ester BTAs, 13 members) have been studied, either in the bulk or in cyclohexane solutions, by means of a series of analytical methods (NMR, DSC, POM, FT-IR, UV-Vis, CD, ITC, high-sensitivity DSC, SANS). Two types of hydrogen-bonded species have been identified and characterized: the expected amide-bonded helical rods (or stacks) that are structurally similar to those formed by BTAs with simple alkyl side chains (alkyl BTAs), and ester-bonded dimers in which the BTAs are connected by means of hydrogen bonds linking the amide N-H and the ester C[double bond, length as m-dash]O. MM/MD calculations coupled with simulations of CD spectra allow for the precise determination of the molecular arrangement and of the hydrogen bond pattern of these dimers. Our study points out the crucial influence of the substituent attached on the amino-ester α-carbon on the relative stability of the rod-like versus dimeric assemblies. By varying this substituent, one can precisely tune the nature of the dominant hydrogen-bonded species (stacks or dimers) in the neat compounds and in cyclohexane over a wide range of temperatures and concentrations. In the neat BTAs, stacks are stable up to 213 °C and dimers above 180 °C whilst in cyclohexane stacks form at c* > 3 × 10-5 M at 20 °C and dimers are stable up to 80 °C at 7 × 10-6 M. Ester BTAs that assemble into stacks form a liquid-crystalline phase and yield gels or viscous solutions in cyclohexane, demonstrating the importance of controlling the structure of these assemblies. Our systematic study of these structurally similar ester BTAs also allows for a better understanding of how a single atom or moiety can impact the nature and stability of BTA aggregates, which is of importance for the future development of functionalized BTA supramolecular polymers.

Correlation between the Selectivity and the Structure of an Asymmetric Catalyst Built on a Chirally Amplified Supramolecular Helical Scaffold.

For the first time, supramolecular helical rods composed of an achiral metal complex and a complementary enantiopure monomer provided a good level of enantioinduction in asymmetric catalysis. Mixtures containing an achiral ligand monomer (BTA(PPh2), 2 mol %) and an enantiopure ligand-free comonomer (ester BTA, 2.5 mol %), both possessing a complementary benzene-1,3,5-tricarboxamide (BTA) central unit, were investigated in combination with [Rh(cod)2]BArF (1 mol %) in the asymmetric hydrogenation of dimethyl itaconate. Notably, efficient chirality transfer occurs within the hydrogen-bonded coassemblies formed by BTA Ile and the intrinsically achiral catalytic rhodium catalyst, providing the hydrogenation product with up to 85% ee. The effect of the relative content of BTA Ile as compared to the ligand was investigated. The amount of chiral comonomer can be decreased down to one-fourth of that of the ligand without deteriorating the enantioselectivity of the reaction, while the enantioselectivity decreases for mixtures containing high amounts of BTA Ile. The nonlinear relationship between the amount of chiral comonomer and the enantioselectivity indicates that chirality amplification effects are at work in this catalytic system. Also, right-handed helical rods are formed upon co-assembly of the achiral rhodium complex of BTA(PPh2) and the enantiopure comonomer BTA Ile as confirmed by various spectroscopic and scattering techniques. Remarkably, the major enantiomer and the selectivity of the catalytic reaction are related to the handedness and the net helicity of the coassemblies, respectively. Further development of this class of catalysts built on chirally amplified helical scaffolds should contribute to the design of asymmetric catalysts operating with low amounts of chiral entities.