Triptycene-Derived Macrocyclic Arenes: From Calixarenes to

Article Cite This: Acc. Chem. Res. XXXX, XXX, XXX−XXX

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Triptycene-Derived Macrocyclic Arenes: From Calixarenes to Helicarenes Published as part of the Accounts of Chemical Research special issue “Supramolecular Chemistry in Confined Space and Organized Assemblies”. Chuan-Feng Chen*,†,‡ and Ying Han† †

Acc. Chem. Res. Downloaded from pubs.acs.org by KAROLINSKA INST on 08/23/18. For personal use only.

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China ‡ University of Chinese Academy of Sciences, Beijing 100049, China CONSPECTUS: The development of new types of synthetic macrocyclic hosts is always one of the most important and attractive topics in macrocyclic and supramolecular chemistry. Calixarenes, resorcinarenes, cyclotriveratrylenes, pillararenes, and their analogues are all composed of hydroxy-substituted aromatic rings bridged by methylene or methenyl groups and thus can be considered a type of macrocyclic arenes. Because of their unique structural features, easy functionalization, and wide applications in many research areas, such macrocyclic arenes have become some of the most important and studied synthetic macrocyclic hosts during the last decades. Triptycene and its derivatives are a class of organic molecules having unique three-dimensional rigid structures, and they have proved to be useful building blocks for constructing new synthetic macrocyclic hosts with specific structures and properties. Dihydroxy-substituted triptycene derivatives are readily available compounds, which encouraged us to conduct studies of triptycene-derived macrocyclic arenes about 10 years ago. Consequently, a series of triptycene-derived calixarenes and analogues containing 1,8-dihydroxy-substituted triptycene subunits were conveniently synthesized. With 2,7-dihydroxy-substituted triptycene as a precursor, new types of calixarene, oxacalixarene, and homooxacalixarene analogues were also obtained. These triptycene-derived macrocyclic hosts all showed fixed conformations in solution and exhibited expanded cavities compared with the corresponding typical calixarenes and analogues. The special structural features also make these triptycene-derived macrocycles show wide potential applications in molecular recognition and self-assembly. In particular, it was found that the threading direction and the orientation based on macrocycles with nonsymmetric structures could be finely controlled by adjusting the electrostatic and steric effects of the guests, which could form the oriented [2]rotaxane by unidirectional threading. We recently developed a new kind of chiral macrocyclic arenes named helicarenes that are composed of chiral 2,6-dihydroxy-substituted triptycene subunits bridged by methylene groups. It was found that the helicarenes not only exhibited convenient synthesis, high stability, good solubility, fixed conformations, and easy functionalization but also showed complexation abilities with various chiral and achiral organic guests. In particular, the switchable complexation based on these macrocycles could be efficiently controlled by multiple stimuli, including acid/base, redox, anion, or light stimuli under a photoacid. Moreover, the helicarenes have also found applications in the construction of interlocked molecules and molecular machines. This Account summarizes our recent research results on the synthesis and structures of the triptycene-derived macrocyclic arenes and analogues and their applications in host−guest chemistry and molecular assembly. We believe that these macrocyclic arenes, especially helicarenes, could be utilized as new synthetic hosts and find wide potential applications in macrocyclic and supramolecular chemistry.

1. INTRODUCTION

Since these macrocyclic hosts are all composed of hydroxysubstituted aromatic rings bridged by methylene or methenyl groups, we can consider them a type of macrocyclic arenes. Previously, we13,14 developed new synthetic hosts by the combination of triptycene building blocks having unique Y-shaped rigid structures and crown ether chains. The rigid triptycene moiety permits these hosts to generate multicavity structures, while the flexible crown ether moiety facilitates adjustment of

Since calixarenes were first efficiently synthesized and named by Gutsche and co-workers in the late 1970s, they and their analogues,1−3 including resorcinarenes,4 cyclotriveratrylenes,5 pillararenes,6−8 and others,3,9−12 have attracted much attention during the last decades. Because of their unique structural features, easy functionalization, and wide applications in many research areas, calixarenes and their analogues have become some of the most important and studied synthetic macrocyclic hosts, and calixarenes have also been called “the third generation of host molecules”, after crown ethers and cyclodextrins.1 1

© XXXX American Chemical Society

Received: June 6, 2018

A

DOI: 10.1021/acs.accounts.8b00268 Acc. Chem. Res. XXXX, XXX, XXX−XXX

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Accounts of Chemical Research the host conformation to the guests. This structure property allows the hosts to demonstrate diversified complexations with various guest molecules and, in particular, multiple-stimuliresponsive binding abilities, which are useful for the design and construction of functionalized supramolecular assemblies. Recently, we also incorporated tritopic triptycene-derived tris(crown ethers) into the design and construction of molecular switches and machines.15−17 Dihydroxy-substituted triptycene derivatives 1a−c (Figure 1) are readily available compounds.18 With 1a as the building

Scheme 1. Synthesis of C2A2Ts 4 and 5

Figure 1. Structures of dihydroxy-substituted triptycenes 1a−c.

block, new triptycene-derived calixarene analogues could be obtained, while 1b could be incorporated into the design and synthesis of other calixarene analogues and also oxacalixarene analogues. By the use of chiral triptycene building block 1c, new chiral macrocyclic arenes composed of subunit 1c bridged by methylene groups could be achieved. This Account highlights our endeavors on the synthesis, structures, and applications in supramolecular chemistry of triptycene-derived macrocyclic arenes, including calixarenes and their analogues, especially helicarenes, a new kind of chiral macrocyclic arenes recently developed by our group.

Figure 2. Structures of C2A2Ts 7 and 8.

When 6a or 6b was reacted with 2,6-dihydroxymethylphenols 15a−b in refluxing xylene, triptycene-derived calix[5]arenes or calix[3]arene[1]triptycenes (C3A1Ts) 16a−c were obtained in 21−25% yield (Scheme 3). Treatment of 16a−c with BBr3 gave the corresponding demethylated products 17a−c in 86−90% yield. De-tert-butylated products 18a and 18b were obtained in 82 and 75% yield by treatment of 17a and 17b with AlCl3, respectively. Under the same conditions, 16a and 16b could be simultaneously de-tert-butylated and demethylated to give 18a and 18b in high yields.22 With 19 as the precursor, dibromo-substituted C3A1T 21 was obtained by a synthetic strategy similar to that shown above (Scheme 4).23 Suzuki−Miyaura cross-coupling of 21 with phenylboronic acid easily produced C3A1T 22 with a deeper cavity. Treatment of 22 with dimethyl sulfate gave the fully methyl etherified C3A1T 23a in 85% yield. Probably because of a lack of the intramolecular hydrogen bonds, 23a adopted a 1,2-alternating conformation, which is different from 22 with a cone conformation. Treatment of 16a with excess bromine in CH2Cl2 interestingly produced pentabromosubstituted C3A1T 24 in a cone conformation in 92% yield (Scheme 5). Reaction of 24 and dimethyl sulfate with potassium carbonate as the base gave 25 in 72% yield, which also adopted a 1,2-alternating conformation. Furthermore, Suzuki− Miyaura coupling of 25 with phenyl or p-methylphenylboronic acids produced the corresponding C3A1T derivatives 23a and 23b with deep cavities in 67 and 63% yield, respectively.23 Calixresorcinarenes or resorcinarenes4 are macrocyclic hosts related to the classical calixarenes. Recently, we24 conveniently synthesized a series of calixresorcinarene-like hosts 32a−c by the reaction of 31a−c and equimolar amounts of triptycene derivative

2. TRIPTYCENE-DERIVED CALIXARENES, OXACALIXARENES, AND ANALOGUES 2.1. Synthesis

If one or more 1,8-dihydroxytriptycene (i.e., 1a) moieties take the place of the phenol groups in a classic calix[4]arene, new kinds of calixarenes with large cavities and fixed conformations can be obtained. Therefore, the pair of diastereomeric triptycenederived calix[6]arenes, or calix[2]arene[2]triptycenes (C2A2Ts), 4a and 5a were synthesized in 19 and 17% yield, respectively (Scheme 1, route a), by one-pot reaction of triptycene derivative 2 with 1 equiv of 3a in a catalytic amount of p-toluenesulfonic acid.19 Similarly, 4b and 5b were synthesized in 17 and 11% yield, respectively, from 2 and 3b. We also obtained 4a (25%), 4b (20%), 5a (19%), and 5b (17%) by the fragment-coupling approach (Scheme 1, route b).20 Treatment of 4a−b and 5a−b with BBr3 produced the corresponding demethylated C2A2Ts 7a−b and 8a−b (Figure 2) in 71−78% yield. Treatment of 7a and 8a with AlCl3 produced de-tert-butylated C2A2Ts 7c and 8c in 61 and 54% yield, respectively. We also found that treatment of 4a and 5a with AlCl3 in toluene directly gave 7c and 8c, respectively, in moderate yields.20 Reaction of 2 with an excess of 2-methyl-1,3-dimethoxybenzene (9a) in CH2Cl2 with BF3·Et2O as the catalyst gave 10a in 76% yield, which was then reacted with 2 in the presence of BF3·Et2O to afford 11a and 12a in 29 and 23% yield, respectively (Scheme 2). Demethylation of 11a and 12a by BBr3 in CH2Cl2 gave 13 and 14 in 86 and 83% yield, respectively. Similarly, 11b−d and 12b−d were also obtained. Further demethylation of 11d and 12d by BBr3 in CH2Cl2 gave 13 and 14 in 90 and 86% yield, respectively.21 B


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Accounts of Chemical Research Scheme 2. Synthesis of 11−14

Scheme 3. Synthesis of 16−18

Scheme 4. Synthesis and Reaction of Dibromo-Substituted C3A1T 21

29 with p-toluenesulfonic acid as a catalyst. Then, treatment of 32a−c with BBr3 produced the corresponding demethylated macrocycles 33a−c in high yields (Scheme 6). 2,7-Dihydroxytriptycene could also be utilized as the nucleophilic reagent for the design and synthesis of oxacalixarenes by

nucleophilic aromatic substitution reactions.25 As a result, reactions of 2,7-dihydroxytriptycene (1b) and electrophilic reagents 34a−b in DMSO with Cs2CO3 or K2CO3 as the base conveniently afforded oxacalixtriptycenes 35a−b and 36a−b C


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Accounts of Chemical Research Scheme 5. Synthesis and Reaction of Pentabromo-Substituted C3A1T 24

Scheme 6. Synthesis of Macrocycles 32 and 33

with extended cavities (Scheme 7a).26 35c and 36c could be synthesized by treatment of 1b with 34c using K2CO3 as the base, and they could also be obtained by the fragment-coupling approach. Similarly, macrocycle 35d was conveniently synthesized in 37% yield by treatment of 1b with 34d in refluxing 1,4-dioxane with Cs2CO3 as the base.27 Treatment of 1b with 34d in DMSO with Cs2CO3 as the base afforded 35d and 36d in 17 and 9% yield, respectively.28 By means of the two-step fragment-coupling approach, 38a was also synthesized in good yield with paraquat as a template. The reaction of 38a with aniline in acetone in the presence of K2CO3 gave 38b in 78% yield (Scheme 7b).29 Compared with oxacalixarenes, homooxacalixarenes with the linking heteroatoms replaced by CH2OCH2 or OCH2 groups

have larger cavities and show different recognition properties. Recently, we30 conveniently synthesized triptycene-derived homooxacalixarene analogues 39a−d and 40a−d in moderate yields by treating 1b with 1,3-bis(bromomethyl)benzene derivatives using Cs2CO3 as the base. Similarly, we also obtained “basketlike” homooxacalixtriptycenes 41a−b and 42a−b (Figure 3). 2.2. Structures in Solution

Macrocycles 4a and 5a are a pair of diastereomers in which 4a with the two same-oriented triptycene moieties is a syn isomer and 5a with the two differently oriented triptycene moieties is an anti isomer.19 Variable-temperature 1H NMR spectra showed that both of the diastereomers have highly symmetric structures and fixed conformations in solution even at high D


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Accounts of Chemical Research Scheme 7. Synthesis of Oxacalixtriptycenes 35, 36, and 38

calix[4]arene.22 For 16a, variable-temperature 1H NMR experiments showed that its coalescence temperature is greater than 100 °C, which is much higher than those of the classic p-tertbutylcalix[4]arene and p-tert-butylcalix[5]arene.1 This indicated that the significant contributor in determining the conformational mobility of 16a is not the intramolecular hydrogen bonds and the bulky tert-butyl groups but rather the introduction of the triptycene moiety having a rigid structure. Similarly, 21, 22, and 24 with different substituents at the upper rim also kept fixed cone conformations in solution due to the rigid structure of the triptycene units and the intramolecular hydrogen bonding of the adjacent phenol hydroxyl groups. However, after 22 and 24 were all methyl etherified, the resulting products 23 and 25 showed 1,2-alternating conformations over the tested temperature ranges.23 Calixresorcinarene-like hosts 32 and 3324 are all cis isomers with fixed cone conformations in solution. Similar to C2A2Ts, oxacalixtriptycenes 35a−d and 36a−d are also pairs of diastereomers, in which 35a−d are cis isomers and 36a−d are trans isomers.26,28 Similarly, homooxacalixarenes 39a−d30 are cis isomers and 40a−d are trans isomers. Moreover, because the two p-phenyl-substituted benzene rings in 41 and 42 are linked with crown ether chains, no conformational changes up to 380 K were observed.

Figure 3. Structures of 39−42.

temperatures. Similarly, 4b and 5b, 7a−c and 8a−c, 11a−d and 12a−d, and 13 and 14 are also diastereomers with symmetric structures and fixed conformations in which the former compounds are syn isomers and the latter ones are trans isomers.20,21 C3A1Ts 16−18 adopted fixed cone conformations in solution as well, although they have larger cavities than the classic

2.3. Structures in the Solid State

The crystal structures of C2A2Ts showed that 4a is a cis isomer with a boat conformation while 5a is a trans isomer with a chair conformation (Figure 4).19 For 7a, a classical cone conformation with a highly symmetric C2v feature was revealed. E


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Accounts of Chemical Research

Figure 4. Crystal structures of (a) 4a, (b) 5a, (c) 7a, (d) 13d, (e) 16a, (f) 17a, (g) 24, and (h) 25.

Because of intramolecular hydrogen bonding in 7a, its dihedral angle between the face-to-face p-tert-butylphenol rings is reduced to 7.44°, compared with 138.23° for its precursor 4a. Moreover, the cavity cross-section of 7a ranged from 9.56 Å × 12.09 Å to 7.91 Å × 8.84 Å.20 Macrocycle 7c has a structural feature similar to that of 7a, and the dihedral angle between the face-to-face phenolic rings is only 6.95°. For 13d containing two 2-methylresorcenyl subunits, a structural feature similar to that of 7a was also observed.21 The crystal structures of C3A1T 16a and its demethylated derivative 17a showed they adopted cone conformations (Figure 4e,f).22 Pentabromo-substituted C3A1T 24 also was in a cone conformation, but 25 in which all of the phenol hydroxyl groups were methyl etherified showed a 1,2-alternating conformation, presumably because of a lack of intramolecular hydrogen bonding (Figure 4h).23 Both macrocycles 32a and 33a are cis isomers with cone conformations in the solid state (Figure 5a,b).24 Since there exist a pair of intramolecular hydrogen-bonding interactions in 32a and two pairs of intramolecular hydrogen-bonding interactions with distances of 1.91−1.99 Å in 33a, 33a shows a more symmetrical structure than 32a, and the dihedral angle of 9.47° between the face-to-face aromatic rings in 33a is much smaller than that in 32a (30.06°). For oxacalixtriptycenes 35a and 36a, the cis isomer 35a has a 1,3-alternating conformation, while the trans isomer 36a shows a chairlike conformation.26 The cis isomer 35d also shows a 1,3-alternating conformation with cavity dimensions of 13.29 Å × 10.99 Å and 8.56 Å × 8.84 Å, in which the N atoms in the 1,8-naphthyridine are all inside the cavity (Figure 5d).27

Figure 5. Crystal structures of (a) 32a, (b) 33a, (c) 35a, and (d) 35d.

2.4. Molecular Recognition

With large enough cavities and specific fixed conformations, triptycene-derived calixarenes and analogues can easily encapsulate small organic molecules in their solid states. For example, 5a encapsulates two CH3OH molecules, and 7c contains one water molecule inside its cavity (Figure 6a,b).20 Similarly, C3A1Ts could also encapsulate small neutral guest molecules (Figure 6c).22 Moreover, calixresorcinarene-like host 32a prefers to form a head-to-head dimeric capsule via two pairs of C−H···O hydrogen-bonding interactions between the methyl protons of one triptycene moiety and the methoxy groups of its adjacent macrocycle, with two CH2Cl2 molecules located in this capsule (Figure 6d).24

Figure 6. Crystal structures of (a) 2CH3OH@5a, (b) H2O@7c, (c) CH2Cl2@16a, and (d) 2CH2Cl2@32a2.

C2A2Ts have enough large and well-defined electron-rich cavities to encapsulate fullerenes as well.20 Consequently, 4b and 5b were found to form stable 1:1 complexes with C60 and C70 with association constants (Ka) greater than 1 × 104 M−1 as measured by fluorescence titrations. These Ka values are higher than those typically measured for 1:1 complexes between F


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Figure 7. Structures of guests 43, 44, and 45.

complexation abilities toward bipyridinium salts, but the affinities of 38b toward the guests were substantially stronger, probably because of the additional non-covalent interactions between the aniline group and the guests.29 Formation of the complexes was further evidenced by the crystal structures of 35d·43a, 35d·43f, and 38b·43i (Figure 8). Interestingly, formation and dissociation of the complex based on 35d containing 1,8naphthridine subunits could be efficiently controlled not only by acid/base stimuli but also by the addition and removal of Hg2+ ions.28 It was further found that 35d showed a highly selective fluorescence sensing toward Hg2+.32 Moreover, 35d could encapsulate π-extended viologens 44 and 45 to form pseudo[3]rotaxane-type complexes in both solution and the solid state, and the host−guest complexation could be reversibly switched by acid/base stimuli. The nonsymmetric structure of 35d also resulted in orientationally selective pseudorotaxanes depending on the length of the linker in the guest, which might be ascribed to different complexation modes between the components in the complexes.33

Figure 8. Crystal structures of (a) 35d·43a, (b) 35d·43f, (c) 38b·43i, and (d) 35d·45a.

2.5. Molecular Self-Assembly

C60 and the classical calixarene derivatives (9−1300 M−1).31 This probably suggests that introducing the triptycene moiety fixes the conformation of the macrocycle and also enhances the interaction between the concave cavity of the macrocycle and the electron-deficient convex surface of the fullerene. Oxacalixtriptycene 35d with an extended cavity could form 1:1 complexes with C60 and C70 as well, and the Ka values for 35d·C60 and 35d·C70 were (7.54 ± 0.29) × 104 and (8.96 ± 0.31) × 104 M−1, respectively.27 Similarly, homooxacalixtriptycene analogues 39a−d and 40a−d also showed efficient complexation abilities toward fullerenes C60 and C70, with Ka > 104 M−1 for the 1:1 complexes.30 Macrocycle 13 with electron-rich cavities could encapsulate paraquat derivatives 43a−d (Figure 7) to form 1:1 complexes, and all of the Ka values were >102 M−1.21 Oxacalixtriptycenes 35d and 36d having sufficiently large cavities and fixed conformations could encapsulate paraquat derivatives to form 1:1 complexes as well, and the Ka values were about 103 M−1 for 35d and 102 M−1 for 36d.28 Similarly, 38a showed moderate

Macrocycles with rigid triptycene moieties can self-assemble into supramolecular structures in the solid state. As a result, it was found that both isomers 4a and 5a can self-assemble into tubular structures and further 3D microporous architectures with solvent molecules inside the channels.19 Macrocycle 32a and its demethylated derivative 33a can form dimeric capsules, which further self-assemble into tubular structures. Similarly, oxacalixtriptycene 35a can form organic nanotubes by virtue of C−Cl···Cl, C−Cl···O, and C−Cl···π interactions.26 By multiple intermolecular chlorine-bonding interactions, 36a and 35c can also assemble into organic tubular structures and further porous architectures. On the basis of complexation between 13 and the paraquat derivative, a [2]rotaxane-type assembly was synthesized in 28% yield.21 Similarly, we also synthesized two isomeric [2]rotaxanes 46a and 46b based on 35d and 36d, respectively, which represent the first examples of oxacalixarenes as wheels for the synthesis of mechanically interlocked molecules.

Figure 9. Chemical structures of [2]rotaxanes 46a and 46b and the crystal structure of 46a. G


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Scheme 8. (a) [2]Rotaxanes 48 and 49 Formed by Directional Threading; (b) [2]Rotaxane 51 Formed by Unidirectional Threading

Scheme 9. Synthesis and Resolution of (±)-56

investigate the directional complexation between the macrocycle and a nonsymmetric guest. Their 1H NMR spectra and crystal structures unequivocally showed that the bipyridinium guests 47a and 47b preferred to thread from the triptycene rim, giving [2]rotaxanes 48a and 49a as the major products.

The formation of [2]rotaxane 46a was further evidenced by its crystal structure (Figure 9).28 Oxacalixtriptycene 35d with an upper semicavity encircled by two naphthyridine subunits and a lower semicavity encircled by two triptycene subunits encouraged us to further H


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Accounts of Chemical Research Scheme 10. Synthesis of Enantiopure (+)-55 and (−)-55

Scheme 11. Synthesis of Hexabromo-Substituted Helic[6]arene Derivatives and Their Suzuki-Miyaura Coupling Reactions

Figure 10. Crystal structure of (±)-56.

Figure 11. Crystal structures of (a) 57a and (b) (+)-P-59.

molecular recognition and self-assembly.35 Generally, chiral macrocyclic arenes can be obtained by introducing a chiral auxiliary into the macrocyclic skeleton35 or by the strategy of introducing inherent chirality.36,37 Planar chiral pillararenes reported by Ogoshi and co-workers38 represent another type of chiral macrocyclic arenes. Although chiral macrocyclic arenes could be efficiently and directly synthesized from chiral building blocks containing phenol groups, no such examples have been reported before. It was known that 2,6-dihydroxytriptycene is a readily available chiral compound, so based on this chiral triptycene building block, a new kind of chiral macrocyclic arenes composed of 2,6-dihydroxytriptycene subunits bridged by methylene groups could be obtained. Since the macrocycles adopt

With 50 as an axle, unidirectional threading was achieved to give [2]rotaxane 51 as the sole product. Thus, the threading direction and the orientation could be finely controlled by adjusting the electrostatic and steric effects of the guests (Scheme 8).34

3. HELICARENES: NEW CHIRAL MACROCYCLIC ARENES Chiral macrocyclic arenes are among the most important chiral synthetic hosts, and they have shown wide applications in chiral I


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coupling of (±)-59 with arylboronic acids gave the series of helic[6]arene derivatives (±)-60a−f in 55−71% yield. Similarly, starting from (+)-55 and (−)-55, (+)-59 and (−)-59 could be conveniently synthesized as well, and their Suzuki− Miyaura coupling reactions gave the series of enantiomers (+)-60a−f and (−)-60a−f in good yields (Scheme 11).40 3.2. Structural Characterization

Macrocycle (±)-56 has a C3-symmetric structure. Its variabletemperature 1H NMR spectra showed no obvious methylene proton signal changes between −40 and 120 °C, indicating that the macrocycle adopted a fixed conformation in solution over the wide temperature range tested and thus is obviously different from the behavior of the classical calixarenes1 and pillararenes.6 The crystal structure of (±)-56 (Figure 10) showed distances of 9.0−9.2 Å between the two centers of the opposite aromatic rings, which are similar to or larger than those in pillar[6]arene, β-cyclodextrin, and cucurbit[7]uril. Moreover, the deepened cavity of 5.28 Å in (±)-56 was found, and it was also far larger than the longitudinal thickness of triptycene (2.66 Å).39 According to the CIP priority rules, we first defined the stereochemistries of enantiomers (+)-56 and (−)-56 as P and M, respectively. Then, from the crystal structure of diasteromer 57a (Figure 11a), the absolute configuration of its macrocyclic skeleton could easily be determined to be P.39 Moreover, we also obtained the crystal structure of (+)-P-59 (Figure 11b), which further confirmed the absolute configuration of the enantiomeric helicarenes.40

Figure 12. Structures of chiral guests 61−63.

hex-nut-like structures with helical chiral cavities, we call them helicarenes.39 3.1. Synthesis

Starting from commercially available anthracene derivative 52, we first prepared triptycene derivative (±)-54 by three general reaction steps. Then treatment of (±)-54 in tetrachloroethane with p-toluenesulfonic acid as a catalyst gave macrocycle (±)-55 in 15% isolated yield, which was then treated with BBr3 to produce macrocycle (±)-56 in high yield.39 Efficient resolution of (±)-56 was performed by introducing the chiral auxiliary, separation with common column chromatography, and then hydrolysis to give enantiopure (+)-56 and (−)-56 (Scheme 9), which were evidenced by their CD spectra with mirror images. Recently, we40 also performed the chiral resolution of (±)-54 by HPLC on a chiral column, and with (+)-54 and (−)-54 as the precursors, we could conveniently obtain enantiomers (+)-55 and (−)-55, respectively, on gram scales (Scheme 10). Bromination of (±)-55 with Br2 gave (±)-58 in 88% yield, which was treated with BBr3 to produce hexabromo-substituted helic[6]arene derivative (±)-59 in 95% yield. Suzuki−Miyaura

3.3. Applications in Molecular Recognitions and Self-Assembly

Helicarenes (+)-56 and (−)-56 with electron-rich cavities and containing six hydroxyl groups can efficiently and enantioselectively complex with chiral ammonium guests by multiple noncovalent interactions. We tested the complexation between the

Figure 13. Chemical structures of guests 64−70. J


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Accounts of Chemical Research Scheme 12. Synthesis of [2]Rotaxane 72

Figure 14. Crystal structures of (a) (±)-55·64a and (b) (±)-55·65a.

Figure 15. Redox-stimulus-responsive switchable complexation.

chiral hosts and three pairs of chiral guests 61−63 (Figure 12) and found that even without any modification, the chiral macrocycles showed obvious enantioselective recognition toward these chiral guests. Especially, for guest 61, the methylated derivative of 1-indamine, the enantioselectivity was considerably high.39 We41 also found that (±)-55 could form 1:1 complexes with acetylcholine 64a and thiaacetylcholine 64b in both solution and the solid state. Compared with (±)-55, without any modifications, (±)-56 showed stronger complexation abilities

Figure 17. Schematic representation of switchable processes between (±)-55 and the guest controlled by (a) acid/base and (b) photoacid.

toward the two guests, probably because of the additional multiple non-covalent interactions between the hydroxyl groups of (±)-56 and the guests. Therefore, we then tested the complexation between (±)-56 and different kinds of quaternary ammonium salts 64c−m (Figure 13) and found that (±)-56 showed significant complexation toward the wide range of tested guests. Moreover, (±)-55 and (±)-56 could also form 1:1 complexes with different kinds of N-heterocyclic salts 43i and 65a−d and even with TCNQ (66) in both solution and the solid state (Figure 14).41 (±)-55 and (±)-56 could encapsulate tropylium ion (67) to form 1:1 complexes as well.42 Their solutions exhibited color changes, and their UV−vis spectra showed the formation of charge transfer (CT) bands, indicating the CT interactions in the complexes. Especially, formation and dissociation of the complexes could be efficiently controlled by a redox stimulus (Figure 15), and a color change of the solution in this switchable process could be visually observed. Moreover, the redox-responsive cycles for the complex based on (±)-55 could be repeated more than 10 times. In the case of (±)-56, a similar complexation phenomenon was also shown, and the redox-responsive cycle could be repeated at least five times.42

Figure 16. Schematic representation of switchable complexation between (±)-55 and the guest controlled by (a) acid/base and (b) Cl− ion. K


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Figure 18. (a) Structures of chiral rotaxanes 73−75, (b) light-driven shuttle motion of 73 by the PIPT strategy, and (c) sustainability of photocontrolled motion.

We43 proved (±)-55 could encapsulate protonated tertiary ammonium guests 68a−h to form 1:1 complexes and also found that small substituent groups on the N atoms or an electron-withdrawing group on the aromatic ring of the guests could be beneficial for the host−guest complexation. Especially, the switchable complexation between the macrocycle and the ammonium guests could be efficiently controlled by acid/base stimuli (Figure 16a) and also by the addition and removal of chloride ion (Figure 16b). Moreover, on the basis of host−guest complexation, we further synthesized 72, the first helicarenebased [2]rotaxane (Scheme 12). (±)-55 can also encapsulate protonated pyridinium guests 69a−c to form 1:1 complexes,44 and the formation and dissociation of the host−guest complexes can be efficiently controlled by acid/base (Figure 17a) and also by light stimuli with the photoacid 1-MEH45 (Figure 17b). Furthermore, we designed and synthesized chiral rotaxanes 73−7546 and found that the shuttle, oscillation, and palindromic motion of (±)-55 between the protonated pyridium site and the alkyl group site could be efficiently controlled by sunlight in the presence of 1-MEH through a photoinduced proton transfer (PIPT) strategy (Figure 18), which also provides the systems with excellent repeatability of more than 50 cycles.

Figure 19. Acid/base-controllable complexation between 76 and quaternary phosphonium salts.

More recently, we47 have also found that the 2,6-helic[6]arene derivative containing six carboxylato groups (76) can encapsulate quaternary phosphonium salts 70a−c to form stable 1:1 complexes in water. According to isothermal titration calorimetry experiments, we further determined the association constants for the 1:1 complexes between 76 and guests 70a−c to be over 105 M−1, indicating that the host showed strong complexation abilities toward the tested quaternary phosphonium salts in aqueous solution. Moreover, the formation and L


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Academy of Sciences (XDB12010400) is greatly appreciated. C.-F.C. also thanks all of his co-workers and students for their great contributions reported in this Account.

dissociation of the host−guest complexes could also be efficiently controlled by acid/base stimulus (Figure 19).

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4. CONCLUSION AND PERSPECTIVES We have proved that dihydroxytriptycenes can be employed as useful building blocks for the design and construction of new kinds of macrocyclic arenes and their analogues. Consequently, a series of triptycene-derived macrocyclic arenes and analogues including C2A2Ts, C3A1Ts, triptycene-derived calixresorcinarene-like hosts, oxacalixtriptycenes, and homooxacalixtriptycenes were synthesized. These macrocyclic arenes and analogues all showed expanded cavities and fixed conformations in solution, which allowed them to show good molecular recognition abilities toward different kinds of guests. Moreover, their fixed conformations also make the macrocycles be promising candidates for self-assembly into a variety of supramolecular structures. We have also recently developed new chiral macrocyclic arenes that we have called helicarenes. It was found these helicarenes not only can be conveniently synthesized and show high stability, good solubility, fixed conformations, and easy functionalization but also exhibit wide complexation abilities with different organic guests. In particular, the switchable complexation based on the macrocycles can be efficiently controlled by multiple stimuli, including acid/base, redox, anion, or light stimuli under photoacid. The chemistry of triptycene-derived macrocyclic arenes, especially helicarenes, is just in its infancy. Further investigation can include various functionalizations of the helicarenes, the development of new members of the helicarene family, and studies of heterohelicarenes, homooxahelicarenes, and their analogues. Importantly, a wide range of potential applications of the new macrocyclic hosts in supramolecular chemistry will be explored. With their special structural features and varied complexation behavior, we believe that triptycene-derived macrocyclic arenes, especially helicarenes, can become a new class of synthetic hosts and thus attract more and more attention in macrocyclic and supramolecular chemistry in the near future.

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REFERENCES

(1) Gutsche, C. D. Calixarenes Revisited; Monographs in Supramolecular Chemistry; Royal Society of Chemistry: Cambridge, U.K., 1998. (2) Calixarenes 2001; Asfari, Z., Böhmer, V., Harrowfield, J., Vicens, J., Saadioui, M., Eds.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 2001. (3) Calixarenes and Beyond; Neri, P., Sessler, J. L., Wang, M.-X., Eds.; Springer: Cham, Switzerland, 2016. (4) Sliwa, W.; Kozlowski, C. Calixarenes and Resorcinarenes: Synthesis, Properties and Applications; Wiley-VCH: Weinheim, Germany, 2009. (5) Hardie, M. J. Recent Advances in the Chemistry of Cyclotriveratrylene. Chem. Soc. Rev. 2010, 39, 516−527. (6) Pillararenes; Ogoshi, T., Ed.; Royal Society of Chemistry: Cambridge, U.K., 2016. (7) Xue, M.; Yang, Y.; Chi, X.; Zhang, Z.; Huang, F. Pillararenes, A New Class of Macrocycles for Supramolecular Chemistry. Acc. Chem. Res. 2012, 45, 1294−1308. (8) Ogoshi, T.; Yamagishi, T.-a.; Nakamoto, Y. Pillar-Shaped Macrocyclic Hosts Pillar[n]arenes: New Key Players for Supramolecular Chemistry. Chem. Rev. 2016, 116, 7937−8002. (9) Chen, H.; Fan, J.; Hu, X.; Ma, J.; Wang, S.; Li, J.; Yu, Y.; Jia, X.; Li, C. Biphen[n]arenes. Chem. Sci. 2015, 6, 197−202. (10) Dai, L.; Ding, Z.-J.; Cui, L.; Li, J.; Jia, X.; Li, C. 2,2′Biphen[n]arenes (n = 4−8): One-Step, High-Yield Synthesis, and Host−Guest Properties. Chem. Commun. 2017, 53, 12096−12099. (11) Georghiou, P. E.; Li, Z.; Ashram, M.; Chowdhury, S.; Mizyed, S.; Tran, A. H.; Al-Saraierh, H.; Miller, D. O. Calixnaphthalenes: Deep, Electron-Rich Naphthalene Ring-Containing Calixarenes. The First Decade. Synlett 2005, 2005, 879−891. (12) Parvari, G.; Annamalai, S.; Borovoi, I.; Chechik, H.; Botoshansky, M.; Pappo, D.; Keinan, E. Multifarenes: New Modular Cavitands. Chem. Commun. 2014, 50, 2494−2497. (13) Han, Y.; Meng, Z.; Ma, Y.-X.; Chen, C.-F. Iptycene-Derived Crown Ether Hosts for Molecular Recognition and Self-Assembly. Acc. Chem. Res. 2014, 47, 2026−2040. (14) Chen, C.-F. Novel Triptycene-Derived Hosts: Synthesis and Their Applications in Supramolecular Chemistry. Chem. Commun. 2011, 47, 1674−1688. (15) Meng, Z.; Han, Y.; Wang, L.-N.; Xiang, J.-F.; He, S.-G.; Chen, C.-F. The Stepwise Motion in a Multivalent [2](3)Catenane. J. Am. Chem. Soc. 2015, 137, 9739−9745. (16) Meng, Z.; Chen, C.-F. A Molecular Pulley Based on a Triptly Interlocked [2]Rotaxane. Chem. Commun. 2015, 51, 8241−8244. (17) Meng, Z.; Wang, B.-Y.; Xiang, J.-F.; Shi, Q.; Chen, C.-F. The Self-Assembly Process of a [2](3)Pseudorotaxane: Inchworm Motion Mechanism. Chem. - Eur. J. 2016, 22, 15075−15084. (18) Chen, C.-F.; Ma, Y.-X. Iptycenes Chemistry: From Synthesis to Applications; Springer: Berlin, 2013. (19) Tian, X.-H.; Hao, X.; Liang, T.-L.; Chen, C.-F. TriptyceneDerived Calix[6]arenes: Synthesis, Structure and Tubular Assemblies in the Solid State. Chem. Commun. 2009, 6771−6773. (20) Tian, X.-H.; Chen, C.-F. Triptycene-Derived Calix[6]arenes: Synthesis, Structures and Their Complexation with Fullerenes C60 and C70. Chem. - Eur. J. 2010, 16, 8072−8079. (21) Xia, Y.-X.; Xie, T.; Han, Y.; Chen, C.-F. Triptycene-Derived Calix[6]arene Analogues: Synthesis, Structure and Complexation with Paraquat Derivatives. Org. Chem. Front. 2014, 1, 140−147. (22) Tian, X.-H.; Chen, C.-F. Synthesis, Structures, and Conformational Characteristics of Triptycene-Derived Calix[5]arenes. Org. Lett. 2010, 12, 524−527. (23) Xia, Y.-X.; Han, Y.; Chen, C.-F. Synthesis and Reactions of Triptycene-Derived Bromocalix[5]arenes: Conformational Trans-

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Chuan-Feng Chen: 0000-0002-4347-1406 Notes

The authors declare no competing financial interest. Biographies Chuan-Feng Chen has been working as full professor of organic chemistry at the Institute of Chemistry, Chinese Academy of Sciences (ICCAS) since 2001. His research interests include supramolecular chemistry based on novel synthetic hosts, organic functional materials, and helicene chemistry. Ying Han obtained her Ph.D. in 2013 from ICCAS under the guidance of Professor Chuan-Feng Chen and is now working as an associate professor at ICCAS. Her current research interest is supramolecular chemistry based on triptycene-derived macrocyclic hosts.

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ACKNOWLEDGMENTS Financial support from the National Natural Science Foundation of China (21332008, 91527301, and 21521002) and the Strategic Priority Research Program of the Chinese M


Article

Accounts of Chemical Research formation from Cone to 1,2-Alternate. Eur. J. Org. Chem. 2014, 2014, 1976−1983. (24) Li, P.-F.; Chen, C.-F. Triptycene-Derived Calix[6]resorcinarene-like Hosts: Synthesis, Structure and Self-Assemblies in the Solid State. Chem. Commun. 2011, 47, 12170−12172. (25) Wang, M.-X. Nitrogen and Oxygen Bridged Calixaromatics: Synthesis, Structure, Functionalization, and Molecular Recognition. Acc. Chem. Res. 2012, 45, 182−195. (26) Zhang, C.; Chen, C.-F. Triptycene-Based Expanded Oxacalixarenes: Synthesis, Structure, and Tubular Assemblies in the Solid State. J. Org. Chem. 2007, 72, 3880−3888. (27) Hu, S.-Z.; Chen, C.-F. Triptycene-Derived Oxacalixarene with Expanded Cavity: Synthesis, Structure and Its Complexation with Fullerenes C60 and C70. Chem. Commun. 2010, 46, 4199−4201. (28) Hu, S.-Z.; Chen, C.-F. Triptycene-Derived Oxacalixarenes as New Wheels for Synthesis of [2]Rotaxanes: Acid−Base- and Metal Ion Switchable Complexation Processes. Chem. - Eur. J. 2011, 17, 5424−5431. (29) Wang, H.-X.; Hu, S.-Z.; Meng, Z.; Han, Y.; Chen, C.-F. Synthesis and Structures of Triptycene-Derived Oxacalixarenes with Expanded Cavities: Tunable and Switchable Complexation Towards Bipyridinium Salts. Chem. - Asian J. 2016, 11, 2756−2762. (30) Xie, T.; Hu, S.-Z.; Chen, C.-F. Triptycene-Derived Homooxacalixarene Analogues: Synthesis, Structures, and Complexation with Fullerenes C60 and C70. J. Org. Chem. 2013, 78, 981−987. (31) Georghiou, P. E. Calixarenes and Fullerenes. In Calixarenes and Beyond; Neri, P., Sessler, J. L., Wang, M.-X., Eds.; Springer: Cham, Switzerland, 2016; pp 879−920. (32) Hu, S.-Z.; Chen, C.-F. Hg2+ Recognition by Triptycene-Derived Heteracalixarenes: Selectivity Tuned by Bridging Heteroatoms and Macrocyclic Cavity. Org. Biomol. Chem. 2011, 9, 5838−5844. (33) Wang, H.-X.; Hu, S.-Z.; Shi, Q.; Chen, C.-F. Complexation Between a Triptycene-Derived Oxacalixarene and π-Extended Viologens: Linker-Length-Dependent Orientation of the Macrocycles in Pseudo[3]rotaxanes. Org. Biomol. Chem. 2016, 14, 10481−10488. (34) Wang, H.-X.; Meng, Z.; Xiang, J.-F.; Xia, Y.-X.; Sun, Y.; Hu, S.Z.; Chen, H.; Yao, J.; Chen, C.-F. Guest-Dependent Directional Complexation Based on Triptycene-Derived Oxacalixarene: Formation of Oriented Rotaxanes. Chem. Sci. 2016, 7, 469−474. (35) Wierzbicki, M.; Jędrzejewska, H.; Szumna, A. Chiral Calixarenes and Resorcinarenes. In Calixarenes and Beyond; Neri, P., Sessler, J. L., Wang, M.-X., Eds.; Springer: Cham, Switzerland, 2016; pp 13−42. (36) Zheng, Y.-S.; Luo, J. Inherently Chiral Calixarenes: A Decade’s Review. J. Inclusion Phenom. Mol. Recognit. Chem. 2011, 71, 35−56. (37) Xu, Z.-X.; Zhang, C.; Zheng, Q.-Y.; Chen, C.-F.; Huang, Z.-T. A New Approach to Enantiopure Inherently Chiral Calix[4]arenes: Determination of Their Absolute Configurations. Org. Lett. 2007, 9, 4447−4450. (38) Ogoshi, T.; Akutsu, T.; Yamafuji, D.; Aoki, T.; Yamagishi, T.-a. Solvent- and Achiral-Guest-Triggered Chiral Inversion in a Planar Chiral pseudo[1]Catenane. Angew. Chem., Int. Ed. 2013, 52, 8111− 8115. (39) Zhang, G.-W.; Li, P.-F.; Meng, Z.; Wang, H.-X.; Han, Y.; Chen, C.-F. Triptycene-Based Chiral Macrocyclic Hosts for Highly Enantioselective Recognition of Chiral Guests Containing a Trimethylamino Group. Angew. Chem., Int. Ed. 2016, 55, 5304−5308. (40) Wang, J.-Q.; Li, J.; Zhang, G.-W.; Chen, C.-F. An Efficient Route to Enantiopure (O-Methyl)6-2,6-helic[6]arenes: Synthesis of Hexabromo-Substituted Helic[6]arene Derivatives and Their Suzuki Coupling Reactions. Unpublished results. (41) Zhang, G.-W.; Li, P.-F.; Wang, H.-X.; Han, Y.; Chen, C.-F. Complexation of Racemic 2,6-Helic[6]arene and Its HexamethylSubstituted Derivative with Quaternary Ammonium Salts, NHeterocyclic Salts, and Tetracyanoquinodimethane. Chem. - Eur. J. 2017, 23, 3735−3742. (42) Zhang, G.-W.; Shi, Q.; Chen, C.-F. Formation of ChargeTransfer Complexes Based on a Tropylium Cation and 2,6-

Helic[6]arenes: a Visible Redox Stimulus-Responsive Process. Chem. Commun. 2017, 53, 2582−2585. (43) Shi, Q.; Han, Y.; Chen, C.-F. Complexation Between (Omethyl)6-2,6-Helic[6]arene and Tertiary Ammonium Salts: AcidBase/Chloride Ion Responsive Host-Guest Systems and Synthesis of [2]Rotaxane. Chem. - Asian J. 2017, 12, 2576−2582. (44) Shi, Q.; Chen, C.-F. Switchable Complexation between (OMethyl)6−2,6-helic[6]arene and Protonated Pyridinium Salts Controlled by Acid/Base and Photoacid. Org. Lett. 2017, 19, 3175−3178. (45) Shi, Z.; Peng, P.; Strohecker, D.; Liao, Y. Long-Lived Photoacid Based upon a Photochromic Reaction. J. Am. Chem. Soc. 2011, 133, 14699−14703. (46) Shi, Q.; Meng, Z.; Xiang, J.-F.; Chen, C.-F. Efficient Control of Movements in Non-Photoresponsive Molecular Machines by PhotoInduced Proton-Transfer Strategy. Chem. Commun. 2018, 54, 3536− 3539. (47) Zhang, G.-W.; Han, Y.; Han, Y.; Wang, Y.; Chen, C.-F. Synthesis of a Water-Soluble 2,6-Helic[6]arene Derivative and Its Strong Binding Abilities Towards Quaternary Phosphonium Salts: An Acid/Base Controlled Switchable Complexation Process. Chem. Commun. 2017, 53, 10433−10436.

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Triptycene-Derived Macrocyclic Arenes: From Calixarenes to

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