Synthesis of tetraphenylene derivatives and their recent advances

The synthetic strategies towards tetraphenylene derivatives are comprehensively summarized in this review. Recent advances in the functionalized tetraphenylene skeleton for research into their structurally unique properties are described together with their potential applications.


INTRODUCTION
Tetraphenylene (1, Fig. 1) can also be called tetrabenzocyclooctatetraene or tetrabenzo [8]annulene. Being a member of the polycyclic aromatic group of compounds, initial studies of 1 were centered around exploration of the planarization of cyclooctatetraene (COT) [1]. In more recent years, a tetrabenzo-derivative of COT has been investigated thoroughly due to its interesting chemical properties and theoretical relevance to the discussion of its aromaticity. However, the structure of 1 was found to be a non-planar molecule with a distinct saddle-shaped framework [2,3]. As depicted in Fig. 1, the four benzene rings of 1 form a rigid central eight-membered ring by ortho-annulation, in which two pairs of benzene rings are oriented alternatively above or below the average plane of the molecule. Therefore, the central COT of 1 is 'non-aromatic'. Although the magnitude of inversion barrier had been controversial, with various estimations in the early years, the saddle-shaped geometry of 1 was found to be very stable, which was confirmed by neutron diffraction study and thermal experiments [4,5]. With this geometric rigidity, studies of 1 and its derivatives have led to their application in asymmetric catalysis, liquid crystalline materials, molecular devices, organic light-emitting diodes and others. More recently, the extraordinary geometric characteristics and promising chiral properties of tetraphenylenes have renewed the interest of synthetic chemists to explore new synthetic strategies and to obtain multisubstituted tetraphenylenes.
The structure of tetraphenylene (1) features a central COT ring embedded in benzene rings. Pioneering work in the context of the planar or tub-shaped conformations of COTs, together with studies on their intrinsic properties and potential applications, have already been described in a series of definitive review or account articles [6][7][8][9][10]. The current review will focus on the synthetic methodology of tetraphenylenes, with a particular focus on recent advances in the preparation of novel tetraphenylene derivatives with three-dimensional topology over the last 10 years.

DIRECT SYNTHESIS OF TETRAPHENYLENES
In terms of organic synthesis, tetraphenylene (1) can be viewed as a tetramer of benzyne. However, to date no methods have been described for the realization of 1 by direct polymerization of benzyne. The first synthesis of 1 was reported by Rapson et al. in 1943 via a copper-assisted coupling of a Grignard reagent (Scheme 1) [11]. Since then, numerous approaches towards tetraphenylenes have been documented [6][7][8][9][10]. Generally, the constructions of 1 and its derivatives are summarized as the following methods: (i) pyrolysis and/or metal-catalyzed dimerization of biphenylenes; (ii) the Diels-Alder cycloaddition and subsequent deoxygenation protocol, starting from cyclooctadienediyne; (iii) oxidative coupling reaction of dilithiobiphenyl derivatives; (iv) transition metal-catalyzed double coupling reactions;  (v) inter-and intramolecular cycloadditions of two ortho-phenylene-tethered triynes; (vi) the fold-in oxidative fusion reaction; (vii) the Scholl reaction; and (viii) tetrameric condensations. These methods are discussed below.

Pyrolysis and/or metal-catalyzed dimerization of biphenylenes
Despite the fact that benzyne (4) might be too reactive for tetramerization by cyclization to provide tetraphenylenes, biphenylene (5) can be viewed as a dimer of o-benzyne. Pyrolysis of 5 in liquid phase at a high temperature of 400 • C afforded an essentially quantitative yield (96%) of 1, as reported by Friedman and Lindow in 1967 [12]. The effects of time and temperature on the course of the reaction showed that an efficient dimerization occurred in the liquid phase as a result of a relatively high steady-state concentration of biphenylene diradical (6) (Scheme 2). Notably, large-scale pyrolyses of biphenylene in 20 g were successfully conducted in a stainless steel bomb at 375 • C for 1 h. The reaction temperature was lower when the reaction was carried out in a stainless steel bomb in comparison with glassware, therefore pyrolysis was attempted in a Vycor tube with a small piece of stainless steel tubing as a catalyst, which showed that the formation of 1 6% 7 8 Scheme 3. Synthesis of octamethyltetraphenylene by pyrolysis. 5  was catalyzed by the stainless steel surface. Importantly, the finding of a metal-catalyzed reaction by cleavage and reconnecting the carbon-carbon (C-C) bonds has accelerated later developments in transition metal catalysis. It is noteworthy that the yield of 1 through pyrolysis has been the highest until now. However, substituted tetraphenylene derivatives such as 8 were obtained at an extremely low yield of 6% in the pyrolysis of the corresponding tetramethyl biphenylene (7) (Scheme 3) [13]. In 1961, it was reported that when 5 was heated to a temperature of 100 • C for 7 h in a sealed tube in the presence of one equivalent of bis(triphenylphosphino)nickel dicarbonyl [Ni(CO) 2 (PPh 3 ) 2 ] complex, the reaction gave a small yield of 1 as the only isolable product (Scheme 4) [14]. Later, Eisch examined various nickel complexes for this reaction, and found that the ligands attached to the metal center of nickel complexes played a crucial role in the oxidative insertion into the strained C-C bond of 5 [15]. For example, complex Ni(COD) 2 was unreactive towards 5, whereas Ni(Et 3 P) 4  completely even at 0 • C. Importantly, a dibenzonickelole intermediate (9) was proposed to be involved in the reaction mechanism (Scheme 5). Then, 9 lost Et 3 P and dimerized to a dinuclear nickel complex (10) (R = Et), whose structure was determined by an X-ray diffraction study. However, it is unfortunate that mononuclear 9 could not be isolated for structural characterization. The likely existence of 9 was nonetheless proved by its reactivity with deuterium hydrochloride (DCl), LiAlH 4 , and CO, leading to the respective desired products. Notably, the structures of 9 and 10 lend support to a unified mechanistic scheme for interpreting the nickel-catalyzed Reppe tetramerization reaction of acetylenes to COT [16].
Considering the classical mechanism of Reppe cyclization for COT catalyzed by nickel [16,17], Johnson isolated an asymmetric nickel-nickel bonded intermediate (11) in the reaction of 5 with bis(1,5-cyclooctadiene)nickel and a larger phosphine i-Pr 3 P. The solid-state crystallographic structures of dinuclear species (10) (R = i-Pr) and (11) support their role in a mechanism involving a formal Ni(III)-Ni(I) complex (Scheme 5) [18].
To complement the results of Eisch, Vollhardt impressively utilized a Ni-catalyzed approach for the preparation of tetraphenylenes bearing various substituents. Thus, a mixture of tetrasubstituted tetraphenylenes (13 and 14) (with Et, Ph and Me 3 Si substituents) was yielded using nickel catalysis as shown in Scheme 6 [19].
The central ring strain of 5 facilitates C-C bond cleavage by transition metals. In this way, dimerization of 5 offers an excellent opportunity to study fundamental C-C bond cleavage and formation involving heavy metals. In 1980, Stille reported that di-μ-chloro-bis(norbornadienerhodium) catalyzed the dimerization of 5 to afford 1 at 44% yield at 250 • C [20]. In 1998, Jones reported that at 120 • C, Pt(PEt 3 ) 3 and Pd(PEt 3 ) 3 were able to convert 5 to 1 in a catalytic manner [21,22]. In addition, Pt(PEt 3 ) 3 and Pd(PEt 3 ) 3 cleaved the C-C bond of 5 to give a metal 2,2-biphenyl complex that is also capable of catalyzing the formation of 1 from 5 via the Pt(IV) intermediate (16) (Scheme 7). The resting-state species in the catalytic cycle was the same complex whether Pt(PEt 3 ) 4 or 16 was used as the catalyst. Of note, intermediates 15 and 16 in the catalytic cycle have been identified and characterized by X-ray crystallographic analysis.
Although the strategy of pyrolysis and/or metal-catalyzed dimerization of biphenylenes yields tetraphenylenes, greater effort is needed to examine factors leading to the efficient oxidative addition of metal complexes into biphenylenes. Moreover, current procedures for the preparation of biphenylenes are unsatisfactory because they either need the use of expensive starting materials or produce biphenylenes in only small amounts. As can be seen, the tetraphenylene derivatives obtained by the dimerization of biphenylenes are very limited due to the availability of biphenylenes. In 2005, Gallagher investigated palladacycles, including a pyridine ring in the reactions with 5, for the construction of heterocyclic tetraphenylene derivatives (18a-18c).  The corresponding products were yielded at 36, 16 and 13%, respectively (Scheme 8) [23].

Diels-Alder cycloaddition and subsequent deoxygenation protocol, starting from cyclooctadienediyne
In their initial works exploring the aromatic properties of planar COTs embedded in conjugated polycycles, Wong and Sondheimer firstly synthesized planar dibenzocyclooctadienediyne as a stable compound in 1974 [24,25]. Soon afterwards, a Diels-Alder reaction with furans was used to trap the acetylenic intermediates to furnish endoxides [26,27]; then, the arenes were constructed by extrusion of the oxygen atom from the endoxides. In 1982, a cycloaddition reaction between the highly strained planar diyne 19 with an excess of furan was undertaken to provide endoxide 20, whose deoxygenation with low-valent titanium led to the formation of 1 at a 50% yield (Scheme 9) [28]. This reaction proved to be an extremely practical 'cycloaddition-deoxygenation protocol', paving a new way towards the synthesis of 1 and its analogs.
On the other hand, 1,16-hydroxytetraphenylene (32) was synthesized by this protocol as illustrated in Scheme 10 [33]. As can be seen, starting from dibromide 29, a diyne 30 was generated with t-BuOK. Without further isolation, 30 was allowed to go through a double Diels-Alder reaction with furan to form an endoxide. A subsequent deoxygenation with low-valent titanium furnished 1,16dimethoxytetraphenylene (31) at an 80% yield. Eventually, treatment of 31 with boron tribromide afforded 32 at a 97% yield.
As shown in Scheme 11, Sygula reported the synthesis of buckycatcher 34 by using this protocol [34], in which two corannulenes are linked with a rigid tetraphenylene unit. Tweezer 34 could form a stable inclusion complex with fullerene C 60 (Ka = 8.6 × 10 3 M -1 , toluene-d 8 , determined by NMR titrations), and an X-ray diffraction study of a mixture of 34 and C 60 allowed the determination of the solid-state complex structure. Similar to the aforementioned Diels-Alder cycloaddition and subsequent deoxygenation protocol, tetraphenylenol (42) and its tetramethoxyl analog (41) were synthesized from 1,10-dimethoxydibenzo[a,e]cyclooctene as a precursor in Wong's laboratory [35]. The synthesis of 1,4,5,16-tetrahydroxytetraphenylene was realized by a stepwise Diels-Alder reaction and subsequent reductive cleavage to form the benzene ring. A further procedure of oxidation and reduction introduced another hydroxyl group on the tetraphenylene skeleton (Scheme 12).
The research group of Siegel reported a novel saddle-shaped tetraphenylene derivative (44) containing two fluoranthene subunits [36]. The synthesis was achieved via a Diels-Alder reaction between 43 and 19 (Scheme 13). The X-ray crystallographic structure of 44 revealed a C 2 symmetric molecule with a dihedral angle; the angle between the mean planes of the naphthalene and benzene units is 19.55 o . The twisting is continuous from one naphthalene subunit, through the tetrapheny- lene core, to the naphthalene of the other fluoranthene subunit. Very recently, Whalley and co-workers reported the synthesis of 47 based on a strategy that was similar to the cycloaddition protocol (Scheme 14) [37]. Sulfoxide 45 was employed as a dienophile in the Diels-Alder reaction with 19, providing the adduct 46 at a 14% yield. Under microwave irradiation, palladium-catalyzed arylation of 46 at 180 • C afforded 47 at a 24% yield. Four fused benzenoid rings around the periphery of the molecule (47) provide a highly stable structure. This increased stability over the parent [8] circulene was predicted using Clar's theory of aromatic sextets and is a result of the compound becoming fully benzenoid upon the incorporation of these additional rings.

Oxidative coupling reaction of dilithiobiphenyl derivatives
The coupling reaction of two hydrocarbon fragments with the aid of a transition metal catalyst provides a fundamentally synthetic methodology for C-C bond formation. Following flourishing research over many decades, the coupling reaction accessible via organometallic reagents nowadays has many more possible applications. The first synthesis of tetraphenylene, as previously mentioned, was a homo-coupling reaction of Grignard reagents [11]. Soon after, Wittig prepared o-dilithiobenzene and 2,2 -dilithiobiphenyl from o-phenylenemercury (by treatment of o-dibromobenzene with sodium mercury amalgam). Next, Wittig detailed the homo-coupling reactions of dilithiobiphenyl with various transition metal chlorides [38]. Besides tetraphenylenes, biphenylenes were also generated (Scheme 15). The selectivity between the two compounds is not constant and alters dramatically depending on different reaction factors. Solvents were often found to play a distinct role. It was suggested that tetrahydrofuran (THF) favored the formation of biphenylenes, while Et 2 O favored that of tetraphenylenes. Substituents on the phenyl rings also influenced the outcome of these reactions. Thus, bromo-substituted dilithiobiaryl gave tetraphenylenes (50) as major products, while methoxy-substituted dilithiobiaryl gave the corresponding tetraphenylenes as minor products in both THF and Et 2 O [39]. The structural features of tetraphenylene derivatives possessing various substituents can be manipulated for a variety of uses. For example, hydroxytetraphenylenes as self-assembling building blocks and other scaffolds have been well summarized in our previous paper [8]. In 2002, Wong and co-workers accomplished the synthesis of 1,4,5,8,9,12,13,16-octamethoxyletraphenylene (54) by using this homo-coupling reaction. Moreover, deprotection and oxidation yielded the corresponding tetraquinone (55) for the study of its inclusion property (Scheme 16) [40].
As can been seen, this homo-coupling reaction could be widely applied as the principal preparative method in the realization of tetraphenylenes. Our recent work has revisited the synthesis of these target molecules of hydroxyltetraphenylenes via intermolecular oxidative homo-or crosscoupling reactions of dilithio substrates mediated by copper salts [41]. We showed that the synthetic steps of each hydroxytetraphenylene were fewer than those of routes reported in previous works, and that the overall yields were also higher (Scheme 17). In general, zinc analogs form biphenylenes as primary products rather than tetraphenylenes. However, zincobiaryls, synthesized from their corresponding dilithiobiaryls with ZnBr 2 (Scheme 18), can also undergo homo-coupling with Cu(II) to afford tetraphenylenes. Iyoda and Kabir found that transmetallation of dilithio derivatives from halogen-lithium exchange with zinc bromide give zincacyclopentadiene (61) as a reactive intermediate [42,43]. Treatment with CuBr 2 allowed further transmetallation and octamethoxytetraphenylene (62) formed selectively at a 67% yield through a reductive elimination sequence.
As tetraphenylenes are saddle-shaped and are inherently chiral π -conjugated scaffolds, a sequence of ortho-annulations of tetraphenylenes via rigid C-C bonds could provide oligotetraphenylenes as artificial double-stranded helical structures. In 1997, Rajca   was determined by X-ray crystallographic analysis, and the space-filling model based on X-ray crystallographic data clearly suggested a double helical structure. Additionally, all the enantiomers, i.e. (P)-78, (P)-79 and (P)-80, were also prepared at 12, 9 and 12% isolated yields, respectively (Scheme 24) [49].
Besides tetraphenylenes, a tetrathiophene was prepared by iron-and copper-mediated coupling reactions (Scheme 25). A synthetic procedure for the preparation of 82a and 82b using copper chlorides as promoters was reported by Wang et al. [50]. Even cyclooctatetrathiophenes with different connection sequences could be achieved on the basis of the selectivity of deprotonation of bithiophene-bearing trimethylsilyl groups [51]. Analog 82c was prepared by Marsella et al. with the aim of achieving double helical oligomers (82d-e) utilizing a further coupling reaction [52].

Transition metal-catalyzed double coupling reactions
The usage of a large amount of lithium reagents is very inconvenient from a practical viewpoint. Palladium-catalyzed double coupling protocols, on the other hand, could provide a reliable pathway towards efficient synthesis of tetraphenylenes. In 2012, an intermolecular double Suzuki coupling reaction was disclosed by Wong and co-workers [53]. As shown in Scheme 26, the intermolecular cyclic dimerization between bromide and boronic acid would lead to a straightforward approach toward regio-and stereoselective synthesis of 2,3,10,11tetramethoxy-tetraphenylene. Interestingly, it was found that a mixture of 84 and 85 in equal quantities was obtained, as determined by NMR analysis.
Later, a double Suzuki coupling reaction of diiodobiphenyl with a diboronate reagent was revealed to be a reliable method in the synthesis of tetraphenylene derivatives [49]. By using Pd(dppf)Cl 2 as a catalyst in dimethyl ether (DME), 1,8,9,16-  reports on the preparation of tetramethoxytetraphenylene [41]. By employing this method, a biphenyl trimer (87) was achieved at a 26% yield in the presence of a catalytic amount of Pd(dppf)Cl 2 (Scheme 27).
Thermal decomposition of cyclic dibenziodonium salts in the generation of biphenyl diradicals was attempted as early as 1967. It was also noted that two biphenyl diradicals could combine to form a tetraphenylene skeleton. However, only one example of 1,16-dinitrotetraphenylene was obtained in an extremely low yield of 0.25% [55]. Recently, we employed dibenziodonium salt (92) as a double Suzuki coupling partner and, gratifyingly, 1 was obtained at a 21% isolated yield from 2,2 -biphenyldiboronic acid (Scheme 29) [56]. Han et al. 903 Besides double Suzuki reactions, Pd-catalyzed Ullmann coupling reactions of diiodobiphenyls in an attempt to construct tetraphenylenes were simultaneously reported by the research groups of Xi and Wong [57,58]. Ouyang  LiOEt. As a result, tetraphenylene (1) was gained at a 45% yield [57]. On the other hand, Wong and coworkers developed double Ullmann coupling and cross-coupling reactions catalyzed by palladium acetates in 2-butanone by utilizing sealed-tube techniques [52]. With this method, 12 tetraphenylene derivatives were synthesized directly at yields of 13-51% from the corresponding 2 -diiodobiphenyls (2) (Scheme 30). Cross-coupling between different diiodobiphenyls was therefore realized. Several examples, such as 93c, 93e, 93g, 93h and 93l were confirmed by X-ray crystallographic analyses. Furthermore, a mechanism of palladium-catalyzed double coupling reactions was proposed featuring a palladacycle in the catalytic cycle. Very recently, Zhang and co-workers reported a facile approach for the synthesis of 1 and its derivatives from 2-iodobiphenyls via Pd-catalyzed C-H activation [59]. A variety of substituted tetraphenylenes 94 were prepared in good yields (Scheme 31). It is noteworthy that the reaction can be performed on a gram scale with relatively high efficiency.

Inter-and intramolecular cycloadditions of two ortho-phenylene-tethered triynes
In 2009, Shibata developed a catalytic and enantioselective method for the synthesis of chiral tetraphenylenes based on a [2 + 2 + 2] cycloaddition of triynes [60][61][62]. This approach gave the target tetraphenylene derivatives (96) in good yields (45-93%) with excellent enantioselectivities (up to 99%). It therefore provides a new route to access substituted tetraphenylene derivatives. The presence of a terminal alkyne in 95 is essential for this protocol, as described in the proposed mechanism. Recently, the reaction's scope was further extended to both electron-donating and electron-withdrawing groups on the phenyl ring of 95 [62]. The results suggested that the stereocontrol was dependent on the chiral ligands employed (Scheme 32).

Fold-in oxidative fusion reaction
According to the report by Osuka and co-workers, tetrabenzotetraaza [8]circulene (98) can be synthesized at a good yield of 96% by a 'fold-in' oxidative fusion reaction of a 1,2-phenylene-bridged cyclic tetrapyrrole (97) [63]. X-ray diffraction analysis revealed a planar square structure with a central COT with a slight alternation of bond lengths (Scheme 33).

Scholl reaction
In 2013, Sakamoto and Suzuki reported two saddleshaped tetrabenzo [8]circulenes, which were synthesized by the Scholl reaction of cyclic octaphenylene precursors [64]. Starting materials (99)  precursor 99b, which may prevent the intermolecular oxidation, gave a much high yield of desired 100b when the Scholl reaction was preceded with FeCl 3 in CH 2 Cl 2 (Scheme 34). It was found that the structure of 100a greatly deviated from planarity, and the deep saddle-shape was confirmed by a single-crystal X-ray crystallographic study.

DIRECT ELECTROPHILIC AROMATIC SUBSTITUTION OF TETRAPHENYLENES
After tetraphenylene (1) was realized, Rapson et al. immediately proceeded to perform nitration and bromination reactions on 1 to give monobromo-and tetranitro-tetraphenlene derivatives (Scheme 37) [11]. However, the substituted positions of these products could not be determined easily. Later, Figeys and Dralants, Mislow and co-workers, and Rosdahl and Sandstrom all reported Friedels-Crafts reactions [69][70][71][72][73]. Figeys and Dralants accomplished the acetylation of 1 using acetyl chloride in tetrachlorethane, and 2-acryl mono-substituted products (108) were obtained at a 72% yield [69]. Mislow and co-workers treated 1 with titanium tetrachloride and dichloromethyl methylether in methylene chloride to obtain a mixture of aldehydes (109 and 110) and other mono-substituted products on other positions accompanied by formylation of 1 [70,71]. Obviously, regioselectivity on 1 is poor due to a lack of directing groups. In 2013, Wu and co-workers reported the direct iodination of tetraphenylene derivatives 111 and 112 by using H 5 IO 6 in combination with I 2 . In these reactions, tetraiodo-substituted tetraphenylenes and their iodo-substituted regioisomers were easily obtained in a non-regioselective manner [74]. The mixture was allowed to undergo a palladiumcatalyzed annulation, leading to the synthesis of a series of peri-substituted [8] circulene derivatives (113), all with good yields. Compounds (113) exhibited a unique saddle-shaped structure with an [8]radialenene character (Scheme 38).
In 2014, Wong and co-workers reported their efforts in the synthesis and study of dioxo-, diaza-, dithio-, and diseleno-bridged tetraphenylenes [75]. Structures of these compounds were unambiguously confirmed by X-ray crystallographic analyses, and crystallographic investigations indicated that 115, 116, 117b, 117c and 118 assumed a unique saddle-shaped structure with different packing motifs (Scheme 39).

LATE FUNCTIONALIZATION OF TETRAPHENYLENE DERIVATIVES
In order to study the magnitude of the inversion barriers of tetraphenylene derivatives, manipulations of functional groups of 1 were carried out after successful aromatic substitution of 1 had been achieved [69][70][71][72][73]. For example, 2acetyltetraphenylene (123) was treated with methyl magnesium iodide to give alcohol 121 at a 94% yield. Tetraphenylene derivatives 121-126 were prepared in a similar way (Fig. 3). It is noteworthy that Mislow and co-workers reported the partial resolution of 126 with brucine to afford (+)-126. Furthermore, 2-acetyltetraphenylene (123) and 25 were obtained in high enantiomeric purities by repeated chromatography on swollen microcrystalline triacetylcelluloses in Wong's laboratory [78].
Vollhardt's group employed 14c as a starting material to synthesize a novel polycycle (131)  containing a central tetraphenylene skeleton via a five-step reaction sequence (Scheme 41) [19].
In order to study the potential applications of chiral tetraphenylenes, Wong and co-workers reported an efficient resolution of racemic hydroxyltetraphenylene, as described in Scheme 42. Thus, conversion of racemic tetrahydroxytetraphenylene 58 into its tetra-(S)-camphorsulfonate esters after esterification with (S)-camphorsulfonyl chloride resulted in two diastereomers (132a and 132b). Chromatographic separation and subsequent deprotection afforded enantiopure 1,8,9,16tetrahydroxyltetraphenylene (58) [79,80]. The presence of hydroxyl groups in the tetraphenylene skeleton has provided openings for further chemistry through late functional group transformations.
Using chiral 98 and 137 as building blocks, three enantiopure rod-like compounds (138-140) were synthesized (Fig. 4) [80]. To have a better understanding of the structures of 138-140, the results of density functional theory computation showed that their structures all seemed to be rod-like chains.
On the basis of the chiral unit of 143, several enantiopure helical macrocycles (144, 145 and 146; Fig. 5) containing one tetraphenylene motif were obtained. Platinum(II) complexes were prepared via coordination-driven self-assembly of 143 and platinum species in the presence of a catalytic amount of copper chloride. In particular, the helical macrocycle 146 was formed by self-assembly of (S,S)-or (R,R)-143 with a dimetallic complex under similar conditions. In the course of the study of polyhydroxyltetraphenylene in host-guest chemistry, Wong's group synthesized a tweezer-like host (147) with two dibenzo-24-crown-8 moieties (Scheme 45). Preliminary investigation showed that 147 could form a 1:1 stable complex with paraquat derivative 148 in solution state, and that the association constant for the complex was determined to be Ka = 4.59 × 10 3 M -1 [53].
Furthermore, Wong and co-workers developed a series of crown ether compounds (149) and their corresponding enantiomers were derived from chiral tetrahydroxytetraphenylene 58 in enantiomerically pure forms (Scheme 46) [47]. Enantiomeric recognition properties of these hosts towards Land D-amino acid methyl ester hydrochloride were studied by UV spectroscopic titration. The tetramer hosts exhibited the best enantioselectivities towards   Land D-alanine methyl ester hydrochloride salt, with K L /K D = 4.10 and K D /K L = 3.90, respectively. Starting with 6,7-bismethoxy-2,11dihydroxytetraphenylene, Wong reported three novel tetraphenylene-derived macrocycles (151-153) as macrocyclic hosts (Scheme 47), and 151 and 152 were characterized by X-ray diffraction studies. Structural studies on the relevant macrocyclic hosts showed that the macrocycles possessed well-defined structures with fixed conformations both in solution and in solid state. They demonstrated efficient and unique properties toward complexation with fullerenes C 60 and C 70 in toluene [54].
Considering  [82]. The study of their liquid crystal states showed that these tetraphenylene derivatives displayed mesophases or columnar phases depending on the substituents of alkyl chains. Moreover, anomalous odd-even effects among this type of tetraphenylenes were discovered.
Wong and co-workers also synthesized a group of tetraalkoxy-substituated tetraphenylenes (155 and 157) in both racemic and chiral forms, as depicted in Scheme 49 [83]. The study of their liquid crystalline properties showed that racemic compounds (157), possessing four long chains of -C 12 H 25 and/or -(CH 2 CH 2 O) 4 CH 3 , form stacking nanosheets through self-assembly in polar solvents. In this way, amphiphilic tetraphenylenes could potentially be used as molecular building blocks for supramolecular soft nanomaterials.
In the research field of asymmetric catalysis, an N,P-ligand (S,S)-158 and a series of Brønsted   1). In continuation of asymmetric catalysis using metal complexes, tetraphenylene-based organocatalysts 159-164 were also used in Diels-Alder reactions between anthrone and maleimides. As shown in Scheme 51, the desired Diels-Alder adduct (169) was obtained in good yields (58-92%) but only in moderate enantioselectivities (up to 43% ee). Although only two reports of asymmetric catalysis in this respect have been recorded to date, chiral catalysts based on tetraphenylene skeletons are very promising due to their unique structural features. It is believed that novel chiral tetraphenylene catalysts will appear soon and be applied in various asymmetric reactions in the near future.

FUTURE PERSPECTIVES
Interest in tetraphenylenes will continue in the coming years due to their intrinsic properties and potential applications. Syntheses of tetraphenylenes have recently witnessed significant progress, although the efficient synthesis of tetraphenylene derivatives in large quantities is still challenging. Therefore, to our knowledge, no tetraphenylenes are currently commercially available, which has limited their utilization in a wider sense. Thus, attempts to discover a general and efficient large-scale strategy to synthesize highly functionalized tetraphenylenes remains challenging and rewarding. We firmly believe that more tetraphenylenes will be realized in the future, and that this will lead to the exploration of more interesting characteristics and unique properties of these intriguing molecules.