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.     

Synthesis, structure, and chirality of hydroxyl- and carboxyl-functionalized cubane-like photodimers of 2-naphthalene

Two novel hydroxyl- and carboxyl-functionalized cubane-like photodimers from methyl 2-naphthoate have been successfully achieved under mild conditions. X-ray crystal structures confirm that the cubane-like structure is well retained in these two derivatives and the intermolecular OH?O hydrogen bonding plays an important role in crystal packing. It is of significance that the isolated racemic mixture can be subsequently resolved into two optically pure enantiomers by high-performance liquid chromatography.     

Halogen‐ and Hydrogen‐Bonded Salts and Co‐crystals Formed from 4‐Halo‐2,3,5,6‐tetrafluorophenol and Cyclic Secondary and Tertiary Amines: Orthogonal and Non‐orthogonal Halogen and Hydrogen Bonding,and Synthetic Analogues of Halogen‐Bonded Biological Systems

Co‐crystallisation of, in particular, 4‐iodotetrafluorophenol with a series of secondary and tertiary cyclic amines results in deprotonation of the phenol and formation of the corresponding ammonium phenate. Careful examination of the X‐ray single‐crystal structures shows that the phenate anion develops a C?O double bond and that the C?C bond lengths in the ring suggest a Meissenheimer‐like delocalisation. This delocalisation is supported by the geometry of the phenate anion optimised at the MP2(Full) level of theory within the aug‐cc‐pVDZ basis (aug‐cc‐pVDZ‐PP on I) and by natural bond orbital (NBO) analyses. With sp² hybridisation at the phenate oxygen atom, there is strong preference for the formation of two non‐covalent interactions with the oxygen sp² lone pairs and, in the case of secondary amines, this occurs through hydrogen bonding to the ammonium hydrogen atoms. However, where tertiary amines are concerned, there are insufficient hydrogen atoms available and so an electrophilic iodine atom from a neighbouring 4‐iodotetrafluorophenate group forms an I???O halogen bond to give the second interaction. However, in some co‐crystals with secondary amines, it is also found that in addition to the two hydrogen bonds forming with the phenate oxygen sp² lone pairs, there is an additional intermolecular I???O halogen bond in which the electrophilic iodine atom interacts with the C?O π‐system. All attempts to reproduce this behaviour with 4‐bromotetrafluorophenol were unsuccessful. These structural motifs are significant as they reproduce extremely well, in low‐molar‐mass synthetic systems, motifs found by Ho and co‐workers when examining halogen‐bonding interactions in biological systems. The analogy is cemented through the structures of co‐crystals of 1,4‐diiodotetrafluorobenzene with acetamide and with N‐methylbenzamide, which, as designed models, demonstrate the orthogonality of hydrogen and halogen bonding proposed in Ho’s biological study.     

Halogen bonding-driven formation of supramolecular macrocycles and double helix

Halogen bonding has been used to hold two hydrogen bonded aromatic amide foldamers to form supramolecular macrocycles.     

Self-assembly of helical supramolecular channels from chiral aminopyrimidine hydrogen bonding motifs in the solid state

The H-bond mediated self-assembly of the chiral C₂-symmetric bis-(2-amino-4-chloro-pyrimidines) 3 and 4 allows for the molecular recognition directed generation of helical superstructures. In the former case, unoccupied channel structures defined by the cylindrical interior of the derived supramolecular helix result, as revealed by X-ray crystallographic analysis using a synchrotron source. Upon crystallization, racemic 3 spontaneously resolves to form homochiral crystals exhibiting a helical packing motif identical to that determined for optically pure 3. The data provide insight into the interplay of the different structural and interactional features of the molecular components to the generation of the channel structure and suggest design strategies toward porous organic molecular solids of variable size.     

Theoretical study of the conformational states of triosmium clusters with a chiral µ-1-NH pinane ligand

This paper reports a theoretical investigation of the conformations of triosmium clusters with a chiral pinane ligand (μ-H)Os₃(CO)₁₀(μ-NHC₁₀H₁₇). The potential curves of internal rotation of the organic ligand relative to the N-C bond are plotted for the cluster complexes. The structures of possible conformers are considered, and reasons for their stability are revealed. The barrier of rotation around the N-C bond of the terpenoid is 186.6 kJ/mol for crystals and ∼140 kJ/mol for solutions. Due to this, the free rotation of the ligand is hindered in both cases. The effects of the intra-and intermolecular interactions on the conformational state of the cluster complex are analyzed. Original Russian Text Copyright ? 2007 by V. A. Potemkin, V. A. Maksakov, and V. S. Korenev __________ Translated from Zhurnal Strukturnoi Khimii, Vol. 48, No. 2, pp. 230–235, March–April, 2007.     

Halogen‐bonded adduct of 1,2‐dibromo‐1,1,2,2‐tetrafluoroethane and 1,4‐diazabicyclo[2.2.2]octane

Halogen bonding is an intermolecular interaction capable of being used to direct extended structures. Typical halogen‐bonding systems involve a noncovalent interaction between a Lewis base, such as an amine, as an acceptor and a halogen atom of a halofluorocarbon as a donor. Vapour‐phase diffusion of 1,4‐diazabicyclo[2.2.2]octane (DABCO) with 1,2‐dibromotetrafluoroethane results in crystals of the 1:1 adduct, C₂Br₂F₄·C₆H₁₂N₂, which crystallizes as an infinite one‐dimensional polymeric structure linked by intermolecular N...Br halogen bonds [2.829 (3) Å], which are 0.57 Å shorter than the sum of the van der Waals radii.     

Co-existing Intermolecular Halogen Bonding and Hydrogen Bonding in the Compound Trans-5,10-bis（1-bromodifluoro-acetyl-1-ethoxycarbonyl-methylidene）thianthrene

Trans-5,10-bis(1-bromodifluoroacetyl-l-ethoxycarbonyl-methylidene)thianthrene (1b) was prepared from the reaction of BrCF2COC(N2)CO2Et with thianthrene. X-ray single crystal diffraction analysis showed that the intermolecular halogen bonding and hydrogen bonding coexisted in this compound. The bromine atom acted as an electron acceptor in the halogen bond and an electron donor in the hydrogen bond. It is the first example that the bromine atom acted as such a dual role in the hydrogen and halogen bond.     

Energy-Minimized Structures and Calculated and Experimental Isomer distributions in the hexaamine-cobalt(III) system [Co(L)2]3+ with the chiral facially-coordinating triamine (l = butane-1,2,4-triamine)

Butane- 1,2,4-triamine (trab) is the smallest tridentate aliphatic unsubstituted chiral triamine. With optically pure trab, there are three, with racemic trab five isomers of [Co(trab)₂]³⁺, One of the five isomers is centrosymmetrical, the others are chiral. For one of the isomers, there are four possible conformations (all combinations of chair and skew boat conformations for the chelate six ring of each ligand), for the others there exist only three independent conformers. All sixteen independent structures have been calculated by strain-energy minimization. The calculated isomer distribution, based on total strain energies corrected with statistical entropy contributions (21%:16%:16%:4%:43%, and 40%:30%:30%, for racemic and optically pure trab, respectively) are in excellent agreement with the experimental data based on HPLC and ¹³C-NMR analyses of equilibrium solutions of the hexaamine-Co(III) compounds prepared by oxygenation of aqueous solutions in presence of activated charcoal. The results are also briefly discussed in relation to possible stereoselectivity upon complexation of optically pure trab and a racemic chiral ligand to a transition-metal center.     

Complementary,Cooperative Ditopic Halogen Bonding and Electron Donor-Acceptor π-π Complexation in the Formation of Cocrystals

This study expands and combines concepts from two of our earlier studies. One study reported the complementary halogen bonding and π-π charge transfer complexation observed between isomeric electron rich 4-N,N-dimethylaminophenylethynylpyridines and the electron poor halogen bond donor, 1-(3,5-dinitrophenylethynyl)-2,3,5,6-tetrafluoro-4-iodobenzene while the second study elaborated the ditopic halogen bonding of activated pyrimidines. Leveraging our understanding on the combination of these non-covalent interactions, we describe cocrystallization featuring ditopic halogen bonding and π-stacking. Specifically, red cocrystals are formed between the ditopic electron poor halogen bond donor 1-(3,5-dinitrophenylethynyl)-2,4,6-triflouro-3,5-diiodobenzene and each of electron rich pyrimidines 2- and 5-(4-N,N-dimethyl-aminophenylethynyl)pyrimidine. The X-ray single crystal structures of these cocrystals are described in terms of halogen bonding and electron donor-acceptor π-complexation. Computations confirm that the donor-acceptor π-stacking interactions are consistently stronger than the halogen bonding interactions and that there is cooperativity between π-stacking and halogen bonding in the crystals.     

Disappearing Enantiomorphs: Single Handedness in Racemate Crystals

Although crystallization is the most important method for the separation of enantiomers of chiral molecules in the chemical industry, the chiral recognition involved in this process is poorly understood at the molecular level. We report on the initial steps in the formation of layered racemate crystals from a racemic mixture, as observed by STM at submolecular resolution. Grown on a copper single‐crystal surface, the chiral hydrocarbon heptahelicene formed chiral racemic lattice structures within the first layer. In the second layer, enantiomerically pure domains were observed, underneath which the first layer contained exclusively the other enantiomer. Hence, the system changed from a 2D racemate into a 3D racemate with enantiomerically pure layers after exceeding monolayer‐saturation coverage. A chiral bias in form of a small enantiomeric excess suppressed the crystallization of one double‐layer enantiomorph so that the pure minor enantiomer crystallized only in the second layer.     

Chiral recognition in surface explosion

The vast majority of chiral compounds crystallize into racemic crystals. It has been predicted and was experimentally established as a rule that chiral molecules on surfaces are more easily separated into homochiral domains due to confinement into a plane and lower entropic contributions. We investigated the formation and stability of two-dimensional tartrate crystals on a Cu(110) surface for the racemic mixture for the first time by means of temperature-programmed desorption (TPD), low-energy electron diffraction (LEED), and X-ray photoelectron spectroscopy (XPS). At low coverage, a bitartrate species becomes separated into homochiral domains, while at high coverage a monotartrate species forms a racemic mixture. At the same coverage and lateral arrangement, the thermally induced autocatalytic decomposition reaction occurs for the monotartrate racemate at a lower temperature than for the pure enantiomers. The stereochemistry in this so-called "surface explosion" reaction is explained by a higher stability of the enantiopure lattice due to lateral hydrogen-bond formation. The higher stability of the enantiopure two-dimensional lattice is in contrast to the higher stability of racemic three-dimensional tartaric acid crystals but is consistent with the observation that homochirality is preferred in hydrogen-bonded self-assembled biomolecular structures.     

Enantiospecific synthesis of vicinal stereogenic tertiary and quaternary centers by combination of configurationally-trapped radical pairs in crystalline solids

[reaction: see text] Photochemical irradiation of crystalline (2R,4S)-2-carbomethoxy-4-cyano-2,4-diphenyl-3-butanone 1 led to highly efficient decarbonylation reactions. Experiments with optically pure and racemic crystals showed that the intermediate radical pairs undergo a highly diastereo- and enantiospecific radical-radical combination that leads to the formation of two adjacent stereogenic centers in good chemical yield and with high chemical control. Reactions with chiral crystals occurred with quantitative enantiomeric yields and >95% diastereomeric yields.     

Chiral induction from ligands to metal centres. A copper(II)–nitroxide complex

Copper(II) complexes of a racemic mixture of a chiral nitronyl-nitroxide are characterised. One, A, is a centro-symmetrical species where two enantiomers are coordinated to a metal centre. The second, B, is a 1D compound comprising bridging ligands through the oxyl and pyridyl donor sites. One observes that, although the crystals are racemic, within a chain, all ligands and metal centres have respectively the same chirality. Possibilities of obtaining optically active extended structures through chiral induction from nitroxide ligands to metal ions are discussed in relation with molecular spin transition species.     

Ab initio investigation of the complexes between bromobenzene and several electron donors: some insights into the magnitude and nature of halogen bonding interactions

Halogen bonding, a specific intermolecular noncovalent interaction, plays crucial roles in fields as diverse as molecular recognition, crystal engineering, and biological systems. This paper presents an ab initio investigation of a series of dimeric complexes formed between bromobenzene and several electron donors. Such small model systems are selected to mimic halogen bonding interactions found within crystal structures as well as within biological molecules. In all cases, the intermolecular distances are shown to be equal to or below sums of van der Waals radii of the atoms involved. Halogen bonding energies, calculated at the MP2/aug-cc-pVDZ level, span over a wide range, from -1.52 to -15.53 kcal/mol. The interactions become comparable to, or even prevail over, classical hydrogen bonding. For charge-assisted halogen bonds, calculations have shown that the strength decreases in the order OH- > F- > HCO2- > Cl- > Br-, while for neutral systems, their relative strengths attenuate in the order H2CS > H2CO > NH3 > H2S > H2O. These results agree with those of the quantum theory of atoms in molecules (QTAIM) since bond critical points (BCPs) are identified for these halogen bonds. The QTAIM analysis also suggests that strong halogen bonds are more covalent in nature, while weak ones are mostly electrostatic interactions. The electron densities at the BCPs are recommended as a good measure of the halogen bond strength. Finally, natural bond orbital (NBO) analysis has been applied to gain more insights into the origin of halogen bonding interactions.     

Effect of intermolecular hydrogen bonding on the molecular structures of imidazole and 1,2,4-triazole: A study by ab initio molecular orbital calculations

The effect of intermolecular hydrogen bonding in the solid state on the molecular structures of imidazole and 1,2,4-triazole has been studied by SCF ab initio molecular orbital calculations at the HF/6-31G^* level. The crystals of these species contain endless chains of molecules, connected by unusually strong N-H N hydrogen bonds. Our simulation of the crystal field, based on two simple models, unequivocally shows that hydrogen bond formation not only lengthens the N-H bond but also causes a concerted change in the length of two N-C bonds. The change indicates that the contribution of a polar canonical form to the structure of the molecule increases in going from the gaseous phase to the crystal. This provides a rationale for the strong intermolecular hydrogen bond occurring in the solid state. We have also optimized the geometry of the free molecules at the MP2/6-31G^* level, to investigate the effect that correcting for electron correlation has on the equilibrium structure of these systems.     

Supramolecular staircase via self-assembly of disklike molecules at the solid-liquid interface.

A series of soluble hexabenzocoronene (HBC) derivatives with pendant optically active (S)-3,7-dimethyloctanyl and (R,S)-3,7-dimethyloctanyl (mixture of stereoisomers) hydrocarbon side chains with and without a phenylene spacer were assembled into differently ordered arrays at the interface between a solution and the basal plane of highly oriented pyrolytic graphite (HOPG). Molecularly resolved scanning tunneling microscopy (STM) images revealed that all derivatives self-assemble into oriented crystals in quasi-two dimensions. However, while for the alkyl-substituted HBCs (1,4) all of the single aromatic cores within a monolayer exhibit the same contrast in the STM, the single aromatic cores with a phenylene group between the alkyl side chains and the aromatic core (2a,2b,3) exhibit different contrasts within a monolayer. For the disks carrying racemic branched or n-alkyl side chains (2b,3) a random distribution of the two different contrasts within the 2D-crystal is observed, while the optically active phenylene-alkyl-substituted HBC (2a) exhibits a periodical distribution of three contrasts within the monolayer. We attribute the different contrasts of the aromatic cores in the presence of the phenylene groups to a loss of the planarity of the whole molecule and different conformations, which allow the conjugated disks to attain different equilibrium positions above the surface of HOPG. In the case of the optically active side chains a regular superstructure with three distinctly different positions such as in a staircase is attained. The self-assembly processes are governed by the interplay of intramolecular as well as intermolecular and interfacial interactions. In the present case, the interactions may induce both the molecules to acquire well distinct positions along the z axis and to adopt different conformations. The reported results open new avenues of exploration. For instance, the different couplings of conjugated molecules with the substrate at different separations can be investigated by means of scanning tunneling spectroscopy (STS). Furthermore, experiments on the STM tip-induced switching of single molecules embedded in a monolayer appear feasible.     

Neutral Chiral Tetrakis-Iodo-Triazole Halogen-Bond Donor for Chiral Recognition and Enantioselective Catalysis

Halogen bonding represents a powerful tool in the field of noncovalent interactions. However, applications in enantioselective recognition and catalysis remain almost nonexistent, due in part to the distinct features of halogen bonds, including long covalent and noncovalent bond distances and high directionality. Herein, this work presents a novel chiral tetrakis-iodo-triazole structure as a neutral halogen bond donor for both chiral anion-recognition and enantioinduction in ion-pair organocatalysis. NMR-titration studies revealed significant differences in anion affinity between the halogen bonding receptor and its hydrogen bonding parent. Selective recognition of chiral dicarboxylates and asymmetric induction in a benchmark organocatalytic reaction were demonstrated using the halogen bond donor. Inversions in the absolute sense of chiral recognition, enantioselectivity, and chiroptical properties relative to the related hydrogen donor were observed. Computational modeling suggested that these effects were the result of distinct anion-binding modes for the halogen- versus hydrogen-bond donors.     

基于脱硫反应的硫脲基罗丹明B 汞离子荧光化学剂量计的合成及分子氢键的影响

基于汞离子促进硫羰基脱硫的不可逆反应, 合成了两种分别含有丙烯酰基酰肼基硫脲基团和丙烯基酰肼基硫脲基团的罗丹明B 荧光探针(RhBHA 和RhBCH), 用以高选择性、高灵敏度检测水溶液中的Hg²⁺离子. 通过荧光发射光谱和可见光下颜色变化研究了硫羰基所处的化学环境对汞离子促进的脱硫反应的影响. 研究结果表明, 引入罗丹明B荧光生色团后, 分子的“开环-闭环”转换过程与分子内氢键作用没有相互影响, 分子内氢键加速了汞离子的脱硫反应,伴随“开环-闭环”转换过程的颜色变化通过肉眼即可观察到. 此外, 还研究了分子间氢键作用对脱硫反应速率的影响.通过加入汞离子后荧光强度随时间变化的跟踪发现, 若溶剂与RhBHA 形成分子间氢键作用, 会使汞离子诱导的脱硫反应有所迟缓. 这种分子间的氢键作用, 对能促进快速脱硫反应的分子内氢键作用产生影响.     

Axially chiral dilactams. Synthesis,racemization barriers and crystal structures

The racemic as well as optically active dilactams 1 and 2 were prepared as the first representatives of axially chiral dilactams possessing a biaryl axis as the sole element of chirality. Their absolute configurations and inversion barriers were determined. The molecular structure and supramolecular self-assembly of the racemic dilactams directed by hydrogen bonding and aryl–aryl stacking was elucidated by single crystal diffraction analysis.