7Li NMR Spectroscopy: A Tool for Determining Dimerization Constants and Averaged Dimerization Constants of the Monomer/Dimer Equilibrium of Hierarchical Helicates.

7Li nuclear magnetic resonance (NMR) spectroscopy is an ideal tool to study hierarchically assembled helicates of the form Li[Li3L6Ti2]. Internally bound and external lithium ions can be well distinguished by solution- or solid-state NMR spectroscopy and dimerization constants of the monomer/dimer equilibrium can be easily determined in solution. Averaged dimerization constants can be estimated in case of statistical mixtures of helicates formed from mixtures of ligands.

The Monomer-Dimer Equilibrium of Triscatechol Titanium(IV)-Based Hierarchical Helicates as a Tool for the Development of Molecular Balances and Molecular Switches.

ConspectusHierarchical helicates are formed by noncovalent connection of two or more monomeric metal complex units, e.g., by bridging metal cations. A unique kind of hierarchical helicate is obtained from 3-carbonyl substituted catechol ligands with titanium(IV) ions in the presence of lithium cations. This kind of supramolecular complex shows in solution a "monomer-dimer" equilibrium. There are different possibilities (solvent, countercation, substituents at carbonyl unit, etc.) to shift this equilibrium to either the monomer or the dimer side. Thus, the lithium-bridged catecholate-based hierarchical helicates resemble a molecular switch. In this Account, different aspects are discussed of how this unique behavior of the dimeric titanium catecholates can be used for application.Thorough investigation of the energetics of the monomer-dimer equilibrium leads to a deeper understanding of the thermodynamic and kinetic effects of the dimerization (or dissociation) process. In this context, even weak interaction of substituents in the periphery of the complexes can be observed. Hereby on the one hand, solvent effects have an important influence and can be easily evaluated. The thorough understanding of the behavior of the monomer-dimer equilibrium allows one to develop some novel applications. In this respect, the use of the hierarchical helicate-based switch as a platform for reaction control and catalysis is described. Decent enantioselectivities up to ee = 58% can be found in Diels-Alder reactions in the periphery of the dimers, while switching to the monomer as a reaction platform still allows the cycloaddition reaction but turns the selectivity off. Additionally, it is described that catalytically important units can be introduced and hydrogenation reactions as well as Michael-type reactions are catalyzed at the helicates.Covalent connection of two catechol ester units leads to classical helicates. Depending on the alkaline metal cation, those can be switched from a compressed to an expanded form or vice versa. Hereby the monomer-dimer equilibrium is transformed into a structural switch. The switching process can be initiated by removal or addition of lithium cations (e.g., by addition of [2.1.1]cryptand). Alternative switching possibilities are based in the case of glycol bridged helicates on cation translocation isomerism and with thioester derivatives it occurs spontaneously in DMSO. Introduction of chiral tethers results in a three state switch allowing expansion/compression as well as switching of the helicity.

Stereochemical dominance in hierarchically formed helicates.

The competition of different chiral ligands in the control of stereochemistry of hierarchically formed helical coordination compounds is investigated. It is found that sterically demanding chiral units can dominate the chiral induction of the helix even if they are present as a minor species. Hereby the relative strength of stereoinduction of different chiral units can be evaluated.

Cation-translocation based isomerism offers a tool for the expansion of compressed helicates.

A series of compressed M[Li313Ti2] (M = Li, Na, K, Rb, Cs) and expanded helicates M4[13Ti2] has been obtained. The helicates Li3[M13Ti2] or M4[13Ti2] with M = Na+, K+, Rb+, or Cs+ adopt the expanded structure in solution. By crystallization the compressed structures M[Li313Ti2] (M = Na, Rb) are obtained. This represents an example of cation-translocation based isomerism.

Hierarchically assembled helicates as reaction platform - from stoichiometric Diels-Alder reactions to enamine catalysis.

The stereoselectivity of a Diels-Alder reaction within the periphery of hierarchically assembled titanium(IV) helicates formed from mixtures of achiral, reactive and chiral, unreactive ligands was investigated in detail. Following the pathway of the chiral induction, the chiral ligands, solvents as well as substituents at the dienophile were carefully varied. Based on the results of the stoichiometric reaction, a secondary amine-catalyzed nitro-Michael reaction is performed as well which afforded reasonable diastereoselectivities.

Iron(III) Chloride as a Mild Catalyst for the Dearomatizing Cyclization of N-Acylindoles.

A catalytic approach for the preparation of indolines by dearomatizing cyclization is presented. FeCl3 acts as a catalyst to afford tetracyclic 5a,6-dihydro-12H-indolo[2,1-b][1,3]benzoxazin-12-ones in good yields. The cyclization also proceeds with tosylamides forming C-N bonds in 53% yield.

Alkyl-Alkyl Interactions in the Periphery of Supramolecular Entities: From the Evaluation of Weak Forces to Applications.

Supramolecular chemistry is based on weak intermolecular forces which nevertheless are of importance for chemical processes. In this report the relevance of alkyl-alkyl interactions in supramolecular assemblies is discussed. We show how hierarchically formed helicates can be used to evaluate weak interactions of alkyl groups based on solvent-supported London dispersion. In addition, the role of nano-segregation of alkyl groups in the periphery of supramolecular assemblies is described, as well as how this can be used to improve the properties of liquid-crystalline materials by controlling the alkyl-chain-mediated aggregation process.

Solvent Dependence of the Monomer-Dimer Equilibrium of Ketone-Substituted Triscatecholate Titanium(IV) Complexes.

Hierarchical helicates based on ketone-substituted titanium(IV)triscatecholates show different monomer-dimer behavior depending on different solvents. The dimerization constants of a whole series of differently alkyl-substituted complexes is analyzed to show that the solvent has a very strong influence on the dimerization. Hereby, effects like solvophobicity/philicity, sterics, electronics of the substituents and weak side-chain-side-chain interactions seem to act in concert.

Stability of Hierarchically Formed Titanium(IV) Tris(catecholate ester) Helicates with Cyclohexyl Substituents in DMSO.

A cyclohexyl substituent strongly prefers the chair conformation with large substituents in equatorial positions, while other cycloalkyls are structurally more flexible. In hierarchically formed dimeric titanium(IV) tris(catecholates) equatorial versus axial connection of the cyclohexane to the ester results in either a more compact (axial) or more expanded (equatorial) structure. In DMSO solution the axial position results in a compact structure which minimizes solvophobic effects, leading to higher stability. However, computational investigations indicate that additionally intramolecular London dispersion interactions significantly contribute to the stability of the dimer. Thus, weak side-chain-side-chain interactions are responsible for the high stability of cyclohexyl ester derivatives with axial compared to equatorial ester connection.

Catechol Thioesters: Ligands for Hierarchically Formed Lithium-Bridged Titanium(IV) Helicates and Helicate-Based Switches.

The thioester moiety is introduced as a lithium binding unit for the hierarchical formation of titanium(IV) catecholate-based lithium-bridged helicates. In solution, the coordination compounds show a monomer-dimer equilibrium which -in comparison to the oxo esters- is significantly shifted towards the monomers. In addition, the influence of the thioester side chain on the dimerization behavior is investigated and an expansible/compressible molecular switch is synthesized. In the latter case expansion and compression are performed reversibly in methanol, whereas in DMSO spontaneous expansion occurs.

Shedding Light on the Interactions of Hydrocarbon Ester Substituents upon Formation of Dimeric Titanium(IV) Triscatecholates in DMSO Solution.

The dissociation of hierarchically formed dimeric triple lithium bridged triscatecholate titanium(IV) helicates with hydrocarbyl esters as side groups is systematically investigated in DMSO. Primary alkyl, alkenyl, alkynyl as well as benzyl esters are studied in order to minimize steric effects close to the helicate core. The 1 H NMR dimerization constants for the monomer-dimer equilibrium show some solvent dependent influence of the side chains on the dimer stability. In the dimer, the ability of the hydrocarbyl ester groups to aggregate minimizes their contacts with the solvent molecules. Due to this, most solvophobic alkyl groups show the highest dimerization tendency followed by alkenyls, alkynyls and finally benzyls. Furthermore, trends within the different groups of compounds can be observed. For example, the dimer is destabilized by internal double or triple bonds due to π-π repulsion. A strong indication for solvent supported London dispersion interaction between the ester side groups is found by observation of an even/odd alternation of dimerization constants within the series of n-alkyls, n-Ω-alkenyls or n-Ω-alkynyls. This corresponds to the interaction of the parent hydrocarbons, as documented by an even/odd melting point alternation.

Cation-Controlled Formation and Interconversion of the fac/fac and mer/mer Stereoisomers of a Triple-Stranded Helicate.

Two biscatecholester ligands with oligoether spacers were used to prepare dinuclear titanium(IV) triscatecholate based helicates. In the case of Li4 [(1/2)3 Ti2 ], "classical" helicates with three internally bound Li+ ions and syn-oriented ligands in the complex units (fac/fac isomer) were obtained. In the case of the sodium salt Na4 [(2)3 Ti2 ], a different homochiral dinuclear triple-stranded helicate with two internally bound Na+ ions was formed. The complex units are anti-configured, and two of the ligand spacers are connecting internal with external positions of the helicate (mer/mer isomer). Removal of the sodium ions and addition of lithium ions leads to the switching from one topology to the other with an expanded helicate [(2)3 Ti2 ]4- as an intermediate. Switching back to the "non-classical" helicate cannot be observed because severe structural rearrangements would be required.

Kinetic investigation of the dissociation of dinuclear hierarchically assembled titanium(iv) helicates.

Hierarchically assembled helicates consisting of lithium-bridged triscatecholate titanium(iv) complexes represent a powerful self-assembled supramolecular system with applications as e.g. molecular balances for the evaluation of weak interactions, stereoselectivity switches in asymmetric synthesis or molecular switches. Their applications or properties are based on the monomer-dimer equilibrium which can be easily observed in solution. The dimer is the only species in the crystal. After dissolution, the dimer slowly dissociates into the monomer until the equilibrium is reached. This can be observed by NMR spectroscopy to investigate the kinetics of the dissociation process. A strong steric effect can be observed by studying differently substituted ligands. Activation energies of the dissociation process can be correlated with the size of the ester substituents and the system may be described as a molecular buckle.

From Hierarchical Helicates to Functional Supramolecular Devices.

Catechol ligands with aldehyde, ketone or ester groups attached in 3-position form, in the presence of titanium(IV) triscatecholate, titanium(IV) complexes. If lithium cations are the counterions, they can bind in a successive step to the salicylate units of the complex and form a dimeric triple-lithium-bridged dinuclear helicate. In solution, the dimer is in equilibrium with the monomer and the thermodynamics of the dimerization can be easily evaluated. Thus, the hierarchically assembled titanium(IV) helicates represent a lithium-dependent molecular switch. The investigation of different derivatives of the complex allows for an estimation of the influence of side chain functionalities on the energetics of the dimerization. Thus, the hierarchically assembled helicates can be used as a kind of molecular balance to determine weak interaction energies (solvophobic effects and even dispersive effects). In addition, tethering of two ligands leads to "classical" helicates. Removal or addition of lithium cations allows for a reversible switching between a compressed and expanded state, which in the case of chiral ligands can be even performed stereospecifically.

A Helicate-Based Three-State Molecular Switch.

The control of structural transformations triggered by external signals is important for the development of novel functional devices. In the present study, it is demonstrated that helicates can be designed to structurally respond to the presence of different counterions and to adopt either a compressed or an expanded structure. Reversible switching is not only possible between those two states, furthermore, the twist of the aggregate also can be controlled. Thus, three out of four possible states of a helicate (expanded/left-handed, expanded/right-handed, compressed/left-handed) based on an enantiomerically pure ester bridged dicatecholate ligand are specifically addressed by introduction, exchange, or removal of countercations. This approach is used to reversibly switch between the different states or to successively address them.

Chasing Weak Forces: Hierarchically Assembled Helicates as a Probe for the Evaluation of the Energetics of Weak Interactions.

London dispersion forces are the weakest interactions between molecules. Because of this, their influence on chemical processes is often low, but can definitely not be ignored, and even becomes important in cases of molecules with large contact surfaces. Hierarchically assembled dinuclear titanium(IV) helicates represent a rare example in which the direct observation of London dispersion forces is possible in solution even in the presence of strong cohesive solvent effects. Hereby, the dispersion forces do not unlimitedly support the formation of the dimeric complexes. Although they have some favorable enthalpic contribution to the dimerization of the monomeric complex units, large flexible substituents become conformationally restricted by the interactions leading to an entropic disadvantage. The dimeric helicates are entropically destabilized.

Coordinatively Unsaturated Lanthanide(III) Helicates: Luminescence Sensors for Adenosine Monophosphate in Aqueous Media.

Coordinatively unsaturated double-stranded helicates [(H2 L)2 Eu2 (NO3 )2 (H2 O)4 ](NO3 )4 , [(H2 L)2 Tb2 (H2 O)6 ](NO3 )6 , and [(H2 L)2 Tb2 (H2 O)6 ]Cl6 (H2 L=butanedioicacid-1,4-bis[2-(2-pyridinylmethylene)hydrazide]) are easily obtained by self-assembly from the ligand and the corresponding lanthanide(III) salts. The complexes are characterized by X-ray crystallography showing the helical arrangement of the ligands. Co-ligands at the metal ions can be easily substituted by appropriate anions. A specific luminescence response of AMP in presence of ADP, ATP, and other anions is observed. Specificity is assigned to the perfect size match of AMP to bridge the two metal centers and to replace quenching co-ligands in the coordination sphere.

CF3 : An Electron-Withdrawing Substituent for Aromatic Anion Acceptors? "Side-On" versus "On-Top" Binding of Halides.

The ability of multiple CF3 -substituted arenes to act as acceptors for anions is investigated. The results of quantum-chemical calculations show that a high degree of trifluoromethyl substitution at the aromatic ring results in a positive quadrupole moment. However, depending on the polarizability of the anion and on the substitution at the arene, three different modes of interaction, namely Meisenheimer complex, side-on hydrogen bonding, or anion-π interaction, can occur. Experimentally, the side-on as well as a η(2) -type π-complex are observed in the crystal, whereas in solution only side-on binding is found.

A Supramolecular Chiral Auxiliary Approach: "Remote Control" of Stereochemistry at a Hierarchically Assembled Dimeric Helicate.

Dimeric hierarchically-assembled titanium(IV) helicates are in solvent-dependent equilibrium with the corresponding monomers. Statistically formed mixtures of such complexes bearing chiral stereocontrolling ligands and achiral diene-substituted ligands show high diastereoselectivity and reasonable enantioselectivity in the Diels-Alder reaction with maleimides if the reaction proceeds with the dimer but not with the monomer. Thus, solvent dependent switching between the monomer and dimer enables on/off switching of the enantioselectivity.