Jeanne L. Bolliger

Enantiopure water-soluble [Fe4L6] cages: host-guest chemistry and catalytic activity.

Host-guest chemistry has its origin in biological processes involving molecular recognition through noncovalent interactions, as for example when substrates bind to enzymes. Over the last decade, organic capsules and self-assembled coordination cages have been prepared that are able to encapsulate a variety of guests, increase the rates of chemical reactions, change the course of reactions involving encapsulated molecules, or shift equilibria to stabilize otherwise unstable species. Self-assembled metal-organic capsules based on chiral ligands are of special interest because they possess a chiral internal void which can not only enable enantioselective guest recognition and separation but can also provide an asymmetric microenvironment for stereoselective reactions. Small guest molecules have been observed to be encapsulated by a water-soluble self-assembled tetrahedral M4L6 cage prepared via subcomponent self-assembly from amine, aldehyde and Fe precursors. Here we show how the use of a longer diamino terphenylene subcomponent, bearing chiral glyceryl groups, allows the enantioselective formation of larger water-soluble Fe4L6 capsules. This new cage encapsulates a wider range of guests, including larger molecules such as chiral natural products. We also demonstrate our cage’s ability to accelerate catalytically the hydrolysis of the acetylcholine esterase inhibitor insecticide dichlorvos, which shares key chemical features with the class of organophosphate chemical warfare agents (CWAs). Diaminoterphenylenes 4, SS-4, and RR-4 were prepared in three steps from diiodohydroquinone 1 as shown in Scheme 1. The studies described below were carried out using aqueous stock solutions of-5 (or-5 or 5) prepared from enantiopure SS-4 (or RR-4 or 4), 2-formylpyridine, and FeSO4 in a 6 : 12 : 4 ratio (Scheme 2). Experimental details and characterization data are provided in the Supporting Information (SI). A solution of the deep purple capsule-5 gave FTICR mass spectra consistent with an [Fe4L6] formulation (SI Fig. SS09). Its hydrodynamic radius, determined from DOSY NMR, was 15.25 (± 0.62) Å, which is consistent with the value of 16.1 Å derived from the model showin in Figure 1. This model was energy-minimized using the universal force field (UFF) of ArgusLabs (SI Fig. S005). Scheme 1. (a) i. NaOH, EtOH, ii. 3-chloro-1,2-propanediol; (b) 4nitrophenylboronic acid, K2CO3, 0.05 mol% [2,6-bis[(di-1piperidinylphosphino)amino]phenyl] palladium(II) chloride; (c) H2, 10% Pd / C.

Dichloro-bis(aminophosphine) complexes of palladium: highly convenient, reliable and extremely active suzuki-miyaura catalysts with excellent functional group tolerance.

Dichloro-bis(aminophosphine) complexes are stable depot forms of palladium nanoparticles and have proved to be excellent Suzuki-Miyaura catalysts. Simple modifications of the ligand (and/or the addition of water to the reaction mixture) have allowed their formation to be controlled. Dichlorobis[1-(dicyclohexylphosphanyl)piperidine]palladium (3), the most active catalyst of the investigated systems, is a highly convenient, reliable, and extremely active Suzuki catalyst with excellent functional group tolerance that enables the quantitative coupling of a wide variety of activated, nonactivated, and deactivated and/or sterically hindered functionalized and heterocyclic aryl and benzyl bromides with only a slight excess (1.1-1.2 equiv) of arylboronic acid at 80 degrees C in the presence of 0.2 mol % of the catalyst in technical grade toluene in flasks open to the air. Conversions of >95 % were generally achieved within only a few minutes. The reaction protocol presented herein is universally applicable. Side-products have only rarely been detected. The catalytic activities of the aminophosphine-based systems were found to be dramatically improved compared with their phosphine analogue as a result of significantly faster palladium nanoparticle formation. The decomposition products of the catalysts are dicyclohexylphosphinate, cyclohexylphosphonate, and phosphate, which can easily be separated from the coupling products, a great advantage when compared with non-water-soluble phosphine-based systems.

[Pd(Cl)2{P(NC5H10)(C6H11)2}2]--a highly effective and extremely versatile palladium-based Negishi catalyst that efficiently and reliably operates at low catalyst loadings.

[Pd(Cl)(2){P(NC(5)H(10))(C(6)H(11))(2)}(2)] (1) has been prepared in quantitative yield by reacting commercially available [Pd(cod)(Cl)(2)] (cod=cyclooctadiene) with readily prepared 1-(dicyclohexylphosphanyl)piperidine in toluene under N(2) within a few minutes at room temperature. Complex 1 has proved to be an excellent Negishi catalyst, capable of quantitatively coupling a wide variety of electronically activated, non-activated, deactivated, sterically hindered, heterocyclic, and functionalized aryl bromides with various (also heterocyclic) arylzinc reagents, typically within a few minutes at 100 °C in the presence of just 0.01 mol% of catalyst. Aryl bromides containing nitro, nitrile, ether, ester, hydroxy, carbonyl, and carboxyl groups, as well as acetals, lactones, amides, anilines, alkenes, carboxylic acids, acetic acids, and pyridines and pyrimidines, have been successfully used as coupling partners. Furthermore, electronic and steric variations are tolerated in both reaction partners. Experimental observations strongly indicate that a molecular mechanism is operative.

Solvent Effects upon Guest Binding and Dynamics of a FeII4L4 Cage

Solvent-dependent host-guest chemistry and favoring of otherwise disfavored conformations of large guests has been achieved with an adaptive, self-assembled Fe(II)4L4 coordination cage. Depending on the counterion, this face-capped tetrahedral capsule is soluble either in water or in acetonitrile and shows a solvent-dependent preference for encapsulation of certain classes of guest molecules. Quantitative binding studies were undertaken, revealing that both aromatic and aliphatic guests bind in water, whereas only aliphatic guests bind in acetonitrile. The flexibility of its subcomponent building blocks allows this cage to expand or contract upon guest binding, as studied by VT-NMR, thereby ensuring strong binding of both small and large guests. Upon encapsulation, large guest molecules can adopt conformations which are not thermodynamically favored in the free state. In addition, the chirotopic inner phase of the cage renders enantiotopic guest proton signals diastereotopic in specific cases.

A Triphasic Sorting System: Coordination Cages in Ionic Liquids

Host-guest chemistry is usually carried out in either water or organic solvents. To investigate the utility of alternative solvents, three different coordination cages were dissolved in neat ionic liquids. By using (19) F NMR spectroscopy to monitor the presence of free and bound guest molecules, all three cages were demonstrated to be stable and capable of encapsulating guests in ionic solution. Different cages were found to preferentially dissolve in different phases, allowing for the design of a triphasic sorting system. Within this system, three coordination cages, namely Fe4 L6 2, Fe8 L12 3, and Fe4 L4 4, each segregated into a distinct layer. Upon the addition of a mixture of three different guests, each cage (in each separate layer) selectively bound its preferred guest.

Self-Assembled Coordination Cages and Organic Capsules as Catalytic Supramolecular Reaction Vessels

Host-guest chemistry has undergone an enormous development since the discovery of cyclodextrins more than 100 years ago which has culminated in the preparation of many artificial host molecules that are not only capable of encapsulating a variety of guests but also of promoting reactions inside their cavities. As the environment dramatically influences the behavior of chemical systems, recent years have seen increased interest in the use of the shielded inner phases of synthetic hosts to stabilize reactive species, shift equilibria, or achieve otherwise unfavorable conformations of guest species. Confinement inside hosts has been used to lower the symmetry of guests, thereby creating new means to control the outcomes of asymmetric reactions in the same way that biological systems make extensive use of tailored microenvironments to promote stereospecific reactions by destabilizing the ground state and stabilizing certain transition state geometries. This chapter will focus on the use of self-assembled coordination cages and organic capsules as homogeneous catalytic supramolecular reaction vessels. Modulation of the cavity environment and binding selectivity is relatively easily achieved because small changes to the geometries of building blocks can lead to much larger changes in the structures and properties of the hollow polyhedral coordination cages formed upon self-assembly. As the reaction medium influences the binding of the reactants and products in subtle but important ways, control over host solubility through host framework charge and substituent effects provides further means to control guest binding strengths, selectivity, and dynamics, and thereby a possible way to overcome product inhibition which is often encountered in supramolecular catalysis. A review will be provided over unusual selectivity observed in reactions carried out in metal-organic capsules as a result of structural constraints. Similarly, rate enhancements in bimolecular reactions due to an increase in effective molarity and stabilization of the transition state as well as transformations carried out under unusual conditions—for example, the acid catalyzed hydrolysis of orthoformates under neutral or basic conditions—will be discussed in this chapter. Furthermore, self-assembled coordination cages based on chiral ligands are of particular interest because they provide an asymmetric microenvironment for promoting stereoselective reactions by purely non-covalent interactions. Particular emphasis will be laid on the hydrolysis of organophosphorus species: As an example of the author’s work, the catalytic degradation of the insecticide dichlorvos by a [Fe4L6]8+ cage molecule will be presented, and this report will also include the up-to-date unpublished results obtained from experiments with other organophosphorus insecticides.

[Fe4L6](8+) cages: encapsulation and catalytic degradation of an insecticide.

Chiral bis(diimine) ligands (derived from chiral enantiopure diamines and 2-formylpyridine) enantioselectively self-assemble with an iron (II) salt to either the tetrahedral cage molecule ΔΔΔΔ-[Fe4L6](8+) or its enantiomer, ΛΛΛΛ-[Fe4L6](8+). These versatile water-soluble capsules are capable of binding a wide range of organic guests in their large hydrophobic cavities. Among these guests is the neurotoxic insecticide dichlorvos, for which the ΔΔΔΔ-[Fe4L6](8+) coordination capsule serves as a competent supramolecular catalyst for its hydrolysis.

Anion Exchange Drives Reversible Phase Transfer of Coordination Cages and Their Cargoes

Chemical separations technologies are energetically costly; lowering this cost through the development of new molecular separation methods would thus enable significant energy savings. Molecules could, for example, be selectively encapsulated and separated using coordination cages, which can be designed with cavities of tailored sizes and geometries. Before cages can be used to perform industrially relevant separations, however, the experimental and theoretical foundations for this technology must be established. Using hydrophobic and hydrophilic anions as stimuli, we show that cages can reversibly transfer many times between mutually immiscible liquid phases, thus transporting their molecular cargoes over macroscopic distances. Furthermore, when two cages are dissolved together, sequential phase transfer of individual cage species results in the separation of their molecular cargoes. We present a thermodynamic model that describes the transfer profiles of these cages, both individually and in the presence of other cage species. This model provides a new analytical tool to quantify the hydrophobicity of cages.

Bis[2,6‐bis(dipiperidin‐1‐ylphosphanyloxy)phenyl]bromidopalladium(II)

The title compound, [PdBr(C26H43N4O2P2)], a so-called palladium pincer complex, is a very efficient catalyst for the Suzuki cross-coupling reaction. The Pd atom exhibits a distorted square-planar coordination, typical for PdII complexes.