Elucidating the Binding Mode of Sulfur- and Selenium-Based Cationic Chalcogen-Bond Donors.

For a comparison of the interaction modes of various chalcogen-bond donors, 2-chalcogeno-imidazolium salts have been designed, synthesized, and studied by single crystal X-ray diffraction, solution NMR and DFT as well as for their ability to act as activators in an SN1-type substitution reaction. Their interaction modes in solution were elucidated based on NMR diffusion and chemical shift perturbation experiments, which were supported by DFT-calculations. Our finding is that going from lighter to the heavier chalcogens, hydrogen bonding plays a less, while chalcogen bonding an increasingly important role for the coordination of anions. Anion-π interactions also show importance, especially for the sulfur and selenium derivatives.

Increased Selectivity in Photolytic Activation of Nanoassemblies Compared to Thermal Activation in On-Surface Ullmann Coupling.

On-surface synthesis is a powerful method that has emerged recently to fabricate a large variety of atomically precise nanomaterials on surfaces based on polymerization. It is very successful for thermally activated reactions within the framework of heterogeneous catalysis. As a result, it often lacks selectivity. We propose to use selective activation of specific bonds as a crucial ingredient to synthesize desired molecules with high selectivity. In this approach, thermally nonaccessible products are expected to arise in photolytically activated on-surface reactions with high selectivity. We demonstrate for assembled 2,2'-dibromo biphenyl clusters on Cu(111) that the thermal and photolytic activations yield distinctly different products, combining submolecular resolution of individual product molecules in real-space imaging by scanning tunneling microscopy with chemical identification in X-ray photoelectron spectroscopy and supported by ab initio calculations. The photolytically activated Ullmann coupling of 2,2'-dibromo biphenyl is highly selective, with only one identified product. It starkly contrasts the thermal reaction, which yields various products because alternate pathways are activated at the reaction temperature. Our study extends on-surface synthesis to a directed formation of thermally inaccessible products by direct bond activation. It promises tailored reactions of nanomaterials within the framework of on-surface synthesis based on the photolytic activation of specific bonds.

Synthesis and VCD Spectroscopic Characterization of a Series of Azacryptands from a Chiral Valine-Based Derivative of Tris(2-aminoethyl)amine (TREN).

Utilizing experimental and computational vibrational circular dichroism (VCD) spectroscopy, we explored the conformational preferences of a series of chiral C3 -symmetric octaazacryptands with tris(2-aminoethyl)-amine head groups derived from valine. While the spectra of the smallest azacryptand with p-phenyl linkers and its elongated derivative with p-biphenyls linker were found to match well with the computed spectra, the computed conformational preferences of the m-biphenyl-based azacryptand did not seem to reflect the conformations dominating in chloroform solution. A detailed analysis revealed that structural changes resulting in a collapsed cage structure gave a notably better match with the experiment. It could subsequently be concluded from the VCD analysis, that the octaazacryptands prefer a collapsed structure, which is not predicted by density functional theory (DFT) calculations as the global minimum structures. These findings are expected to have consequences also for future studies on inclusion complexes of such azacryptands.

Chalcogen bonding in the solid-state structures of 1,3-bis(benzimidazoliumyl)benzene-based chalcogen-bonding donors.

1,3-Bis(benzimidazoliumyl)benzene-based chalcogen-bonding catalysts were previously successfully applied in different benchmark reactions. In one of those examples, i.e. the activation of quinolines, sulfur- and selenium-based chalcogen-bonding catalysts showed comparable properties, which is unexpected, as the selenium-containing catalysts should show superior catalytic properties due to the increased polarizability of selenium compared to sulfur. Herein, we present four crystal structures of the respective 1,3-bis(benzimidazoliumyl)benzene-based chalcogen-bonding catalyst containing sulfur (3S) and selenium (3Se, three forms) as Lewis acidic centres. The sulfur-containing catalyst shows weaker chalcogen bonding compared to its selenium analogue, as well as anion-π interactions. The selenium-based analogues, on the other hand, show stronger chalcogen-bonding motifs compared to the sulfur equivalent, depending on the crystallization conditions, but in every case, the intermolecular interactions are comparable in strength. Other interactions, such as hydrogen bonding and anion-π, were also observed, but in the latter case, the interaction distances are longer compared to those of the sulfur-based equivalent. The solid-state structures could not further explain the high catalytic activity of the sulfur-containing catalysts. Therefore, a comparison of their σ-hole depths from density functional theory (DFT) gas-phase calculations was performed, which are again in line with the previously found properties in the solid-state structures.

A Potent Auto-Umpolung Ligand for Conjugative Radical Stabilization.

Carbenes with conjugatively connected redox system act as "auto-umpolung" ligands. Due to their electronic flexibility, they should also be particularly suitable to stabilize open-shell species. Herein, the first neutral radical of such sort is described in form of a dialkylamino-substituted bis(dicyanomethylene)cyclopropanide. Despite the absence of steric shielding, the radical is stable for an extended amount of time and was consequently characterized in solution via EPR measurements. These data and accompanying X-ray structural analyses indicate that the radical species is in equilibrium with aggregates (formed via π-stacking) and dimers (obtained via σ-bond formation between methylene carbons).

Stereochemistry Controls Dihydrogen Bonding Strengths in Chiral Amine Boranes Adducts.

The growing interest in exploiting novel concepts of non-covalent interactions in catalysts and supramolecular chemistry made us revisit a special kind of hydrogen bonding: the dihydrogen bond (DHB), formed between a classical hydrogen bond donor and a hydridic hydrogen as acceptor. Herein, we investigate how the strength of the N-Hδ+ ⋅⋅⋅δ- H-B interaction and hence the DHB-driven self-aggregation of amine-borane adducts is governed by steric effects by comparing the structures and binding enthalpies of various chiral derivatives. For a diastereomeric pair of amine-boranes prepared from a chiral secondary amine, we show that the stereochemistry at the nitrogen has significant influence on the interaction enthalpy. Based on this finding, N-chiral amine boranes can be envisioned to become interesting building blocks in supramolecular chemistry to fine-tune the formation dynamics of assemblies.

Inducing Propeller Chirality in Triaryl Boranes with Chiral Amines.

Stabilization of chiral propeller conformations in triaryl compounds is challenging due to generally low racemization barriers. Nonetheless, it was recently found that chiral conformational preferences can be induced to triaryl boranes by incorporating point-chiral alkylether chains to the aryl blades and subsequently locking the structure with ammonia. A four-point interaction, meaning that the cooperative effects of Lewis-adduct formation and three hydrogen bonds, was proposed as stabilizing mechanism. Herein, it was shown that three such strong interactions suffice to introduce a preferential propeller handedness. Although DFT calculations predict no noteworthy preferences for either P- or M-chiral propellers for some of the investigated triarylborane-amine adducts that were prepared with chiral primary amines, vibrational circular dichroism (VCD) spectroscopic characterizations revealed that there is indeed a measurable excess of one propeller handedness. Furthermore, the steric demand of the amine was found to play a key role in the induction process and especially in preventing blade rotations.

VCD spectroscopy reveals conformational changes of chiral crown ethers upon complexation of potassium and ammonium cations.

Two chiral derivatives of 18-crown-6, namely the host molecules 2,3-diphenyl- and 2-phenyl-18c6, serve as model systems to investigate whether VCD spectroscopy can be used to monitor conformational changes occurring upon complexation of guests. Host-guest complexes of both crown ethers were prepared by addition of KNO3. The more bulky 2,3-diphenyl-18c6 is found to undergo major conformational changes upon encapsulation of K+, which are revealed as characteristic changes of the VCD spectral signatures. In contrast, while 2-phenyl-18c6 also incorporates K+ into the macrocycle, strong conformational changes are not occurring and thus spectral changes are negligible. With an octyl ammonium cation as guest molecule, 2,3-diphenyl-18c6 shows the same conformational and spectral changes that were observed for K+-complexes. In addition, the asymmetric NH3-deformation modes are found to gain VCD intensity through an induced VCD process. An analysis of the vibrational spectra enables a differentiation of VCD active and inactive guest modes: There appears to be a correlation between the symmetry of the vibrational mode and the induced VCD intensity. While this finding makes the host-guest complexes interesting systems for future theoretical studies on the origin of induced VCD signatures, the observations described in this study demonstrate that VCD spectroscopy is indeed a suitable technique for the characterization of supramolecular host-guest complexes.

Dynamic Stereochemistry of a Biphenyl-Bisprolineamide Model Catalyst and its Imidazolidinone Intermediates.

In this study, we characterize the dynamic stereochemistry of a biphenyl-2,2'-bis(proline amide) catalyst in chloroform and DMSO as representative weakly and strongly hydrogen bonding solvents. Using vibrational circular dichroism (VCD) spectroscopy and density functional theory (DFT) based spectra calculations, we show that the preferred axial stereochemistry of the catalyst is determined by solute-solvent interactions. Explicitly considering solvation with DMSO molecules is found to be essential to correctly predict the conformational preferences of the catalyst. Furthermore, we investigate the stereochemistry of the corresponding enamines and imidazolidinones that are formed upon reaction with isovaleraldehyde. The enamines are found to rapidly convert to endo-imidazolidinones and the thermodynamically favored exo-imidazolidinones are formed only slowly. The present study demonstrates that the stereochemistry of these imidazolidinones can be deduced directly from the VCD spectra analysis without any further detailed analysis of NMR spectra. Hence, we herein exemplify the use of VCD spectroscopy for an in situ characterization of intermediates relevant in asymmetric catalysts.

Tracing absorption and emission characteristics of halogen-bonded ion pairs involving halogenated imidazolium species.

We investigate how the absorption and fluorescence of halogenated imidazolium compounds in acetonitrile solution is influenced by the presence of counterions and the ability to act as halogen-bond donors. Experimental measurements and quantum chemical calculations with correlated wavefunction methods are applied to study three monodentate halogen-bond complexes of iodo-imidazolium, iodo-benzimidazolium and bromo-benzimidazolium cations with triflate counterions, and a bidentate complex of bis(iodo-benzimidazolium) dications with chloride as counterion. The three monodentate complexes with triflate counterions relax after photoexcitation to minima on the S1 potential energy surface where the C-I bond and the IO halogen bond are partially broken. For the bidentate complex with the smaller chloride counterion the halogen-bond interaction stays intact in the S1 minimum that is reached by relaxation from the Franck-Condon point. In a complementing experimental approach, stationary absorption and emission as well as transient fluorescence spectra are recorded for iodo- and bromo-benzimidazolium in acetonitrile. Variation of the counterion, substitution of the iodine by bromine, hydrogen, or methyl, and the comparison to theory allows the identification of spectroscopic signatures and photoinduced dynamics associated with ion-pairing.

A Bidentate Iodine(III)-Based Halogen-Bond Donor as a Powerful Organocatalyst*.

In contrast to iodine(I)-based halogen bond donors, iodine(III)-derived ones have only been used as Lewis acidic organocatalysts in a handful of examples, and in all cases they acted in a monodentate fashion. Herein, we report the first application of a bidentate bis(iodolium) salt as organocatalyst in a Michael and a nitro-Michael addition reaction as well as in a Diels-Alder reaction that had not been activated by noncovalent organocatalysts before. In all cases, the performance of this bidentate XB donor distinctly surpassed the one of arguably the currently strongest iodine(I)-based organocatalyst. Bidentate coordination to the substrate was corroborated by a structural analysis and by DFT calculations of the transition states. Overall, the catalytic activity of the bis(iodolium) system approaches that of strong Lewis acids like BF3 .

Chiral Molecular Propellers of Triarylborane Ammonia Adducts.

Chiral molecular propeller conformations have been induced to various triaryl structures including trityl derivatives and triaryl boranes. For borane-amine adducts, such induced propeller chirality has not been reported yet due to the low energy barrier for racemization in common triarylboranes such as B(C6 H5 )3 or B(C6 F5 )3 . Herein, we demonstrate that point chirality in side chains of chiral triarylborane-ammonia adducts, which feature intramolecular hydrogen bonds in addition to the dative N→B bond, can efficiently be transferred to triarylborane propeller chirality. Employing X-ray crystallography and ECD/VCD spectroscopy for structural characterizations, we investigate three examples with different steric demands of the incorporated chiral alkoxy side groups. We elucidate the conformational preferences of the molecular propellers. Furthermore, we show that computationally predicted conformational preferences obtained for the isolated, only implicitly solvated molecules are actually opposite to the experimentally observed ones.

Basis set dependence of S[double bond, length as m-dash]O stretching frequencies and its consequences for IR and VCD spectra predictions.

Benchmarking functionals and basis sets for the computational prediction of molecular properties is usually done on very small model systems. Larger organic molecules containing heavier second row atoms are not the typical model structures. We herein present the first survey of basis sets and functionals for the prediction of the IR and VCD spectra of chiral tosylates and sulfinates as we noted drastic deviations between computed harmonic frequencies obtained at B3LYP/6-311++G(2d,p) level of theory and those observed in experimental solution phase IR and VCD spectra. We show that the harmonic frequencies of the asymmetric and symmetric S[double bond, length as m-dash]O stretching modes of tosylates are predicted at significantly too low vibrational frequencies if the employed basis set does not provide higher order polarization functions. The results of our benchmarks show that at least the 6-311G(3df,2dp) basis (or equivalent Dunning and Ahlrichs variants) should be used.

Hypervalent Iodine(III) Compounds as Biaxial Halogen Bond Donors.

"Hypervalent" iodine(III) derivatives have been established as powerful reagents in organic transformations, but so far only a handful of studies have addressed their potential use as halogen-bonding noncovalent Lewis acids. In contrast to "classical" halogen-bond donors based on iodine(I) compounds, iodine(III) salts feature two directional electrophilic axes perpendicular to each other. Herein we present the first systematic investigation on biaxial binding to such Lewis acids in solution. To this end, hindered and unhindered iodolium species were titrated with various substrates, including diesters and diamides, via 1H NMR spectroscopy and isothermal titration calorimetry. Clear evidence for biaxial binding was obtained in two model systems, and the association strengths increased by 2 orders of magnitude. These findings were corroborated by density functional theory calculations (which reproduced the trend well but underestimated the absolute binding constants) and a cocrystal featuring biaxial coordination of a diamide to the unhindered iodolium compound.

"Anti-Electrostatic" Halogen Bonding.

Halogen bonding is often described as being driven predominantly by electrostatics, and thus adducts between anionic halogen bond (XB) donors (halogen-based Lewis acids) and anions seem counterintuitive. Such "anti-electrostatic" XBs have been predicted theoretically but for organic XB donors, there are currently no experimental examples except for a few cases of self-association. Reported herein is the synthesis of two negatively charged organoiodine derivatives that form anti-electrostatic XBs with anions. Even though the electrostatic potential is universally negative across the surface of both compounds, DFT calculations indicate kinetic stabilization of their halide complexes in the gas phase and particularly in solution. Experimentally, self-association of the anionic XB donors was observed in solid-state structures, resulting in dimers, trimers, and infinite chains. In addition, co-crystals with halides were obtained, representing the first cases of halogen bonding between an organic anionic XB donor and a different anion. The bond lengths of all observed interactions are 14-21 % shorter than the sum of the van der Waals radii.

Bidentate Chiral Bis(imidazolium)-Based Halogen-Bond Donors: Synthesis and Applications in Enantioselective Recognition and Catalysis.

Even though halogen bonding-the noncovalent interaction between electrophilic halogen substituents and Lewis bases-has now been established in molecular recognition and catalysis, its use in enantioselective processes is still very rarely explored. Herein, we present the synthesis of chiral bidentate halogen-bond donors based on two iodoimidazolium units with rigidly attached chiral sidearms. With these Lewis acids, chiral recognition of a racemic diamine is achieved in NMR studies. DFT calculations support a 1:1 interaction of the halogen-bond donor with both enantiomers and indicate that the chiral recognition is based on a different spatial orientation of the Lewis bases in the halogen-bonded complexes. In addition, moderate enantioselectivity is achieved in a Mukaiyama aldol reaction with a preorganized variant of the chiral halogen-bond donor. This represents the first case in which asymmetric induction was realized with a pure halogen-bond donor lacking any additional active functional groups.

Is There a Single Ideal Parameter for Halogen-Bonding-Based Lewis Acidity?

Halogen-bond donors (halogen-based Lewis acids) have now found various applications in diverse fields of chemistry. The goal of this study was to identify a parameter obtainable from a single DFT calculation that reliably describes halogen-bonding strength (Lewis acidity). First, several DFT methods were benchmarked against the CCSD(T) CBS binding data of complexes of 17 carbon-based halogen-bond donors with chloride and ammonia as representative Lewis bases, which revealed M05-2X with a partially augmented def2-TZVP(D) basis set as the best model chemistry. The best single parameter to predict halogen-bonding strengths was the static σ-hole depth, but it still provided inaccurate predictions for a series of compounds. Thus, a more reliable parameter, Ωσ* , has been developed through the linear combination of the σ-hole depth and the σ*(C-I) energy, which was further validated against neutral, cationic, halogen- and nitrogen-based halogen-bond donors with very good performance.

Crystal Engineering with Multipoint Halogen Bonding: Double Two-Point Donors and Acceptors at Work.

The combination of singly or doubly bidentate halogen-bond donors with double bidentate acceptors was investigated as a supramolecular synthon in crystal engineering. The crystal topologies obtained feature novel halogen-bonding motifs like double two-point recognition and infinite chains or networks based on two-point interactions. Induced conformational changes in the double bidentate halogen-bond donors could be exploited to obtain different 1D and 2D networks. All solid-state studies were accompanied by DFT calculations to predict and rationalize the outcome.

Chalcogen Bonding Catalysis of a Nitro-Michael Reaction.

Chalcogen bonding is the non-covalent interaction between Lewis acidic chalcogen substituents and Lewis bases. Herein, we present the first application of dicationic tellurium-based chalcogen bond donors in the nitro-Michael reaction between trans-ß-nitrostyrene and indoles. This also constitutes the first activation of nitro derivatives by chalcogen bonding (and halogen bonding). The catalysts showed rate accelerations of more than a factor of 300 compared to strongly Lewis acidic hydrogen bond donors. Several comparison experiments, titrations, and DFT calculations support a chalcogen-bonding-based mode of activation of ß-nitrostyrene.

A halogen-bonding-catalysed Nazarov cyclisation reaction.

Various neutral, mono- and dicationic halogen bond donors were screened for their ability to act as catalysts in a Nazarov cyclisation reaction. Using a highly preorganized dicationic catalyst with a noncoordinating counterion proved essential for high activity.