Chiral pillar[n]arenes: Conformation inversion,material preparation and applications

Chiral pillar[n]arenes have shown great research value and application prospect in construction of chiral materials and chiral applications, due to their inherent planar chiral configurations, chiral recognition ability, easy modification and highly symmetric hydrophobic cavity. This review systematically summarized the conformation inversion factors of planar chiral pillar[5]arenes (pR/pS), such as solvents, temperature, substituent size, alkyl chains, chiral and achiral guest molecules. We firstly introduced the applications of chiral pillar[n]arenes for constructing chiral materials and pointed out that planar conformation inversion showed a great potential role in constructing chiral materials. Then, we mainly concluded the chiral applications of chiral and planar chiral pillar[n]arenes like chiral enantiomer analysis by circular dichroism, electrochemistry or chiral fluorescence sensing. From this review, we found that the inherent planar chiral conformation of chiral pillar[n]arenes have played a very important role in chiral field in the future.     

Construction of π‐Surface‐Metalated Pillar[5]arenes which Bind Anions via Anion–π Interactions

By simple ligand exchange of the cationic transition‐metal complexes [(Cp*)M(acetone)₃](OTf)₂ (Cp*=pentamethylcyclopentadienyl and M=Ir or Rh) with pillar[5]arene, mono‐ and polynuclear pillar[5]arenes, a new class of metalated host molecules, is prepared. Single‐crystal X‐ray analysis shows that the charged transition‐metal cations are directly bound to the outer π‐surface of aromatic rings of pillar[5]arene. One of the triflate anions is deeply embedded within the cavity of the trinuclear pillar[5]arenes, which is different to the host–guest behavior of most pillar[5]arenes. DFT calculation of the electrostatic potential revealed that the metalated pillar[5]arenes featured an electron‐deficient cavity due to the presence of the electron‐withdrawing transition metals, thus allowing encapsulation of electron‐rich guests mainly driven by anion–π interactions.     

Synthesis and host-guest properties of pillar[6]arenes

A facile method for the synthesis of pillar[6]arenes was developed.A series of pillar[6]arenes were prepared with FeCl 3 as catalyst and chloroform as solvent at room temperature in moderate yields(30%-40%).Their host-guest properties with n-cetyltrimethyl ammonium bromide were investigated by 1 HNMR.The results showed that high selectivity in the host-guest relationship became apparent between pillar[6]arenes and pillar[5]arenes based on the different size of the inner cavity.     

[n]Cycloparaphenylene-Pillar[5]arene Bismacrocycles: Their Circularly Polarized Luminescence and Multiple Guest Recognition Properties

Both pillar[n]arenes (P[n]As) and [n]cycloparaphenylenes ([n]CPPs) play an important role in supramolecular chemistry. Herein, we report the precise synthesis of two multifunctional bismacrocycles [n]CPP-P[5]A by integrating P[5]A into the [n]CPP backbone. The photoluminescence quantum yield (Φ_F) of the bismacrocycles was found to show a dramatic increase relative to the corresponding [n]CPPs. The chiral enantiomers (pR)/(pS)-[8]CPP-P[5]A were successfully isolated by chiral HPLC, and showed promising properties of circularly polarized luminescence (g_lum≈0.02). In addition, [n]CPP-P[5]A bismacrocycles are capable of binding pyridinium salts and fullerene derivatives with high affinity and specificity within the two distinct cavities. Transient absorption studies showed that photo-induced electron transfer occurs in [10]CPP-P[5]A⊃C₆₀ complex. Our results suggest that [n]CPP-P[5]A are potentially useful in CPL-active materials, multiple guest recognition and supramolecular polymer preparation.     

Alignment and Dynamic Inversion of Planar Chirality in Pillar[n]arenes

Pillar[n]arenes are symmetrical macrocyclic compounds composed of benzene panels with para-methylene linkages. Each panel usually exhibits planar chirality and prefers chirality-aligned states. Because of this feature, pillar[n]arenes are attractive scaffolds for chiroptical materials that are easy to prepare and optically resolve and show intense circular dichroism (CD) signals. In addition, rotation of the panels endows the chirality of pillar[n]arenes with a dynamic nature. The chirality in tubular oligomers and supramolecular assemblies sometimes show time- and procedure-dependent alignment phenomena. Furthermore, the CD signals of some pillar[n]arenes respond to the addition of chiral guests when their dynamic chirality is coupled with host–guest properties. By using diastereomeric pillar[n]arenes with additional chiral structures, the response can also be caused by achiral guests and changes of the environment, providing molecular sensors.     

Efficient synthesis of copillar[5]arenes and their host-guest properties with dibromoalkanes

An efficient method for the synthesis of copillar[5]arenes was developed with FeCl(3) as catalyst and different 1,4-dialkoxybenzenes and paraformaldehyde as reactants (yields: 50-85%). The host-guest property of (co)pillar[5]arenes and terminal dibromoalkanes was investigated by (1)H NMR measurements and an X-ray study. The complexation behavior of the copillar[5]arenes can be tuned by changing the substituents on the host. A complete complexation selectivity was found between pillar[5]- and pillar[6]arenes, which is an interesting aspect for sensor techniques.     

Rim-differentiated pillar[5]arenes

Pillar[5]arenes, designed and prepared by Ogoshi et al. in 2008 initially, refer to fifth classical macrocyclics. Among a wide range of pillar[5]arenes, rim-differentiated pillar[5]arenes containing five identical substituents on one rim and five different identical groups on the other rims are considered the most noteworthy type of pillar[5]arenes. As compared with the perfunctionalized pillar[5]arene, the self-assembly properties of rim-differentiated pillar[5]arenes have more varieties. On the other hand, in comparison with other types of pillar[5]arenes, the rim-differentiated pillar[5]arenes exhibit a more rigid symmetrical structure. In the present review, the synthetic methods, host-guest interactions, self-assembly properties and applications of rim-differentiated pillar[5]arenes are summarized. Hopefully, this review will be conducive to researchers in macrocyclic supramolecular chemistry.     

Synthesis and inclusion properties of pillar[n]arenes

A detailed study of the reaction conditions revealed that a quantitative cyclocondensation of 1,4-dialkoxy-2,5-bis(alkoxymethyl)-benzenes to pillar[n]arenes can be achieved by catalysis of p-toluenesulfonic acid in CH₂Cl₂. Major product of this new reaction is in each case a cyclopentamer (n = 5), but small amounts of the pillar[n]arenes with n = 6, 7 and 10 can be obtained as well. Different alkoxy groups in 1- and 4-position lead to regioisomers. All cyclooligomers exist in pillar structures as pair of enantiomers, which show a racemisation at room temperature, which is fast in terms of the NMR time scale. The racemisation process occurs by rotation of the 1,4-phenylene segments in the macrocyclic rings. Pillar[n]arenes exhibit novel host–guest behavior.     

A novel pillar[5]arene-cucurbit[10]uril based host-guest complex: Synthesis,characterization and detection of paraquat

The macrocyclic family comprising pillar[n]arenes and cucurbit[n]urils have received much attention recently. However, studies on the construction of supramolecular complexes formed directly with derivatized pillar[n]arenes and cucurbit[n]urils are scant. Given the interest in such systems, herein we have synthesized a new type of naphthalene-derivatized pillar[n]arene NTP5 and selected Q[10] as the host molecule. The 4-[2-(1-naphthalenyl)ethenyl]pyridine of NTP5 is encapsulated by Q[10] and formed a host-guest complex in water-acetic acid (1:1) solution accompanied by enhanced fluorescence, which changed the morphology of NTP5 from a sphere to a porous form. In addition, the fluorescence of Q[10]-NTP5 can be quenched by the addition of the highly toxic pesticide paraquat (PQ), and the mechanism was shown to be the formation of a new charge transfer ternary system of Q[10]-NTP5-PQ. This work provides new ideas for the contribution of supramolecular assemblies based on derivatized pillar[n]arenes and their combination with cucurbit[n]urils and reveals their potential applications.     

Pillar[6]arenes: From preparation,host-guest property to self-assembly and applications

Pillar[n]arenes primarily comprise pillar[5]arenes and pillar[6]arenes, which belong to the new class of supramolecular macrocyclic hosts. Pillar[n]arenes have aroused wide attention because of their highly rigid and symmetrical architectures, controllable cavity size, and wide applications in a wide variety of areas. Although pillar[6]arene is difficult to synthesize, numerous studies have been conducted on it. In this review, the strategies to synthesize and functionalize pillar[6]arenes are investigated systematically. In addition, their host-guest properties in organic solvents and in aqueous solution are described. Moreover, pillar[6]arenes applied in different fields (e.g., molecular recognition, drug release, cancer therapy, and gas separation) are clarified. Hopefully, this study is capable of arousing more attention from increasing scientists to study large-cavity pillar[n]arenes.     

Synthesis of novel pillar-shaped cavitands “Pillar[5]arenes” and their application for supramolecular materials

In 2008, we reported a new class of macrocyclic hosts and named “Pillar[5]arenes”. They combine the advantages and aspects of traditional hosts and have a composition similar to those of typical calix[n]arenes. Pillar[5]arenes have repeating units connected by methylene bridges at the para-position, and thus they have a unique symmetrical pillar architecture differing from the basket-shaped structure of meta-bridged calix[n]arenes. Pillar[5]arenes show high functionality similar to cyclodextrins, and can capture electron accepting guest molecules within their cavity similarly to cucurbit[n]urils. In this review, the synthesis, structure, rotation, host–guest properties, planar chirality and functionality of pillar[5]arenes are discussed, along with pillar[5]arene-based supramolecular architectures and the challenges in synthesizing pillar[6]arenes.     

Novel [2]rotaxanes based on the recognition of pillar[5]arenes to an alkane functionalized with triazole moieties

Host-guest complexation between an alkane functionalized with triazole moieties and three pillar[5]arenes was studied. Three pillar[5]arene-based [2]rotaxanes were constructed based on this new recognition motif. The sequence of the yields of these [2]rotaxanes was consistent with the order of association constants between the three corresponding pillar[5]arenes and the alkane. ¹H NMR, electrospray ionization mass spectrometry, and NOESY NMR were employed to characterize these [2]rotaxanes.     

Dynamic-to-Static Planar Chirality Conversion in Pillar[5]arenes Regulated by Guest Solvents or Amplified by Crystallization

Controlling dynamic chirality and memorizing the controlled chirality are important. Chirality memory has mainly been achieved using noncovalent interactions. However, in many cases, the memorized chirality arising from noncovalent interactions is erased by changing the conditions such as the solvent and temperature. In this study, the dynamic planar chirality of pillar[5]arenes was successfully converted into static planar chirality by introducing bulky groups through covalent bonds. Before introducing the bulky groups, pillar[5]arene with stereogenic carbon atoms at both rims existed as a pair of diastereomers, and thus showed planar chiral inversion that was dependent on the chain length of the guest solvent. The pS and pR forms, regulated by guest solvents, were both diastereomerically memorized by introducing bulky groups. Furthermore, the diastereomeric excess was amplified by crystallization of the pillar[5]arene. The subsequent introduction of bulky groups yielded pillar[5]arene with an excellent diastereomeric excess (95 % de).     

Pre-regulation of the planar chirality of pillar[5]arenes for preparing discrete chiral nanotubes

Regulating the chirality of macrocyclic host molecules and supramolecular assemblies is crucial because chirality often plays a role in governing the properties of these systems. Herein, we describe pillar[5]arene-based chiral nanotube formation via pre-regulation of the building blocks'' chirality, which is different from frequently used post-regulation strategies. The planar chirality of rim-differentiated pillar[5]arenes is initially regulated by chiral awakening and further induction/inversion through stepwise achiral external stimuli. The pre-regulated chiral information is well stored in discrete nanotubes by interacting with a per-alkylamino-substituted pillar[5]arene. Such pre-regulation is more efficient than post-regulating the chirality of nanotubes.

Pillar[5]arene-based chiral nanotube formation via pre-regulation of the building blocks'' chirality is more efficient than post-regulating the chirality of nanotubes.     

Stereochemical control of calixarenes useful as rigid and conformationally diversiform platforms for molecular design

Stereochemical problems and related functions of calix[4]arenes, calix[6]arenes and their chiral derivatives have been reviewed. In p-tert-butylcalix[4]arene (1H₄) and its mono-, di-, tri-, and tetra-O-alkyl derivatives (1H₃R, 1H₂R₂,1HR₃, and 1R₄, respectively), 23 different homologues can exist (including 1H₄). We found that the OH group in the unmodified phenol unit is permeable through the calix[4]arene ring. Thus, several conformational isomers become equivalent after the ‘oxygen-through-the-annulus’ rotation of the OH group and the number of possible homologues is reduced to 13 (including 1H₃). We report in this paper the syntheses of all of these possible conformational isomers using a protection-deprotection method with a benzyl group and metal template effects. On the other hand, all possible chiral isomers that can be derived from calix[4]arene by modification of the OH groups have been systematically classified. Molecular asymmetry can be generated not only by different substituents but also by conformational isomerism. The numbers of chiral isomers are 17 for tetra-O-substituted calix[4]arenes, 9 for tri-O-substituted calix[4]arenes, 3 for di-O-substituted calix[4]arenes, and 0 for mono-O-substituted calix[4]arenes. Chiral calix[4]arenes can also be designed by the introduction of a substituent into the m-position of a phenol unit or by the use of a dissymmetric ‘stapling reaction’ in proximal phenol units. In p-tert-butylcalix[6]arene, the conformational behaviour is totally different from that in p-tert-butylcalix[4]arene. A large degree of conformational freedom remains in the framework, and both ‘oxygen-through-the-annulus rotation’ and ‘para-substituent-through-the-annulus rotation’ can take place. However, when metal cations are bound to calix[6]aryl esters, the conformation is changed to a cone type. Bridging and capping are powerful methods to immobilize the conformation of calix[6]arenes. In addition, definitive evidence for ring immobilization was obtained from the absence of racemization in the chiral calix[6]arene. A successful example of chiral recognition for α-amino acid derivatives was achieved by using chiral homooxacalix[3]arene which has ‘pseudo C₂ symmetry’. These examples indicate that calixarenes serve as rigid and conformationally diversiform platforms for the design of novel functional supramolecules.     

Host–Guest Complexation Using Pillar[5]arene Crystals: Crystal-Structure Dependent Uptake,Release, and Molecular Dynamics of an Alkane Guest

Host–guest complexation has been mainly investigated in solution, and it is unclear how guest molecules access the assembled structures of host and dynamics of guest molecules in the crystal state. In this study, we studied the uptake, release, and molecular dynamics of n-hexane vapor in the crystal state of pillar[5]arenes bearing different substituents. Pillar[5]arene bearing 10 ethyl groups yielded a crystal structure of herringbone-type 1:1 complexes with n-hexane, whereas pillar[5]arene with 10 allyl groups formed 1:1 complexes featuring a one-dimensional (1D) channel structure. For pillar[5]arene bearing 10 benzyl groups, one molecule of n-hexane was located in the cavity of pillar[5]arene, and another n-hexane molecule was located outside of the cavity between two pillar[5]arenes. The substituent-dependent differences in molecular arrangement influenced the uptake, release, and molecular dynamics of the n-hexane guest. The substituent effects were not observed in host–guest chemistry in solution, and these features are unique for the crystal state host–guest chemistry of pillar[5]arenes.     

Novel P‐Stereogenic PCP Pincer‐Aryl Ruthenium(II) Complexes and Their Use in the Asymmetric Hydrogen Transfer Reaction of Acetophenone

Achiral P‐donor pincer‐aryl ruthenium complexes ([RuCl(PCP)(PPh₃)]) 4c , d were synthesized via transcyclometalation reactions by mixing equivalent amounts of [1,3‐phenylenebis(methylene)]bis[diisopropylphosphine] ( 2c ) or [1,3‐phenylenebis(methylene)]bis[diphenylphosphine] ( 2d ) and the N‐donor pincer‐aryl complex [RuCl{2,6‐(Me₂NCH₂)₂C₆H₃}(PPh₃)], ( 3 ; Scheme 2). The same synthetic procedure was successfully applied for the preparation of novel chiral P‐donor pincer‐aryl ruthenium complexes [RuCl(P*CP*)(PPh₃)] 4a , b by reacting P‐stereogenic pincer‐arenes (S,S)‐[1,3‐phenylenebis(methylene)]bis[(alkyl)(phenyl)phosphines] 2a , b (alkyl=ⁱPr or ^tBu, P*CHP*) and the complex [RuCl{2,6‐(Me₂NCH₂)₂C₆H₃}(PPh₃)], ( 3 ; Scheme 3). The crystal structures of achiral [RuCl(equation/tex2gif-sup-3.gifPCP)(PPh₃)] 4c and of chiral (S,S)‐[RuCl(equation/tex2gif-sup-6.gifPCP)(PPh₃)] 4a were determined by X‐ray diffraction (Fig. 3). Achiral [RuCl(PCP)(PPh₃)] complexes and chiral [RuCl(P*CP*)(PPh₃)] complexes were tested as catalyst in the H‐transfer reduction of acetophenone with propan‐2‐ol. With the chiral complexes, a modest enantioselectivity was obtained.     

Open‐tubular capillary electrochromatography using carboxylatopillar[5]arene as stationary phase

Pillar[n]arenes have achieved much interest in material chemistry and supramolecular chemistry due to unusual pillar shape structure and high selectivity toward guest. However, pillar[n]arenes have not yet been applied in capillary electrochromatography. This work at first time reports that carboxylatopillar[5]arene is used as a stationary phase in open‐tubular capillary electrochromatography. Carboxylatopillar[5]arene not only possess the advantages of pillar[n]arenes but also provide free carboxy groups for immobilizing on the inner wall of capillary column via covalent bonding. The characterization of SEM and FT‐IR indicated that carboxylatopillar[5]arene was successfully grafted on the inner wall of capillary. The baseline separation of model analytes including neutral, basic, and acidic compounds, nonsteroidal anti‐inflammatory drugs and dansyl‐amino acids have been achieved thanks to the electron‐rich cavity of carboxylatopillar[5]arene and hydrophobic interactions between the analytes and stationary phase. The intraday, interday, and column‐to‐column precisions (RSDs) of retention time and peak area for the neutral analytes were all less than 3.34 and 9.65%, respectively. This work indicates that pillar[n]arenes have great potential in capillary electrochromatography as novel stationary phase.     

Sequential Chiral Induction and Regulator-Assisted Chiral Memory of Pillar[5]arenes

Chirality transfer is widely observed in life processes, and many artificial chiral transfer systems have been developed. In these systems, chiral information is transferred from chiral inducers to chiral acceptors by a direct chiral induction process and a direct chiral memorization process. We have developed ternary nondirect chiral transfer systems based on pillar[5]arenes, in which a third factor was introduced as a regulator. The planar chirality of an acceptor was induced and memorized by a chiral inducer with precise control by a regulator. In the chiral induction period, the feed sequence of the chiral inducer and regulator affected the chiral induction behavior of the chiral acceptor. The chiral memory ability of the acceptor was substantially improved by the combined action of the chiral inducer and regulator.     

High-yield diastereoselective synthesis of planar chiral [2]- and [3]rotaxanes constructed from per-ethylated pillar[5]arene and pyridinium derivatives

Planar chiral [2]- and [3]rotaxanes constructed from pillar[5]arenes as wheels and pyridinium derivatives as axles were obtained in high yield using click reactions. The process of rotaxane formation was diastereoselective; the obtained [2]rotaxane was a racemic mixture consisting of (pS, pS, pS, pS, pS) and (pR, pR, pR, pR, pR) forms of the per-ethylated pillar[5]arene (C2) wheel, and other possible types of the [2]rotaxane did not form. Isolation of the enantiopure [2]rotaxanes with one axle through (pS, pS, pS, pS, pS)-C2 or (pR, pR, pR, pR, pR)-C2 wheels was accomplished. Furthermore, pillar[5]arene-based [3]rotaxane was successfully synthesized by attachment of two pseudo [2]rotaxanes onto a bifunctional linker. [3]Rotaxane formed in a 1:2:1 mixture with one axle threaded through two (pS, pS, pS, pS, pS)-C2, one (pS, pS, pS, pS, pS)-C2 and one (pR, pR, pR, pR, pR)-C2 (meso form), or two (pR, pR, pR, pR, pR)-C2 wheels. The [3]rotaxane enantiomers and the meso form were successfully isolated using appropriate chiral HPLC column chromatography. The procedure developed in this study is the starting point for the creation of pillar[5]arene-based interlocked molecules.