Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• observed between the dimer and trimer, despite the same absolute configuration of the planar chiral [2.2]paracyclophane units, which was reproduced by theoretical studies. Keywords: circularly polarized luminescence; oligomer; [2.2]paracyclophane; planar chirality; Introduction Cyclophane is a general

• term for cyclic compounds with at least one aromatic ring in the main chain backbone [1]. Cyclophane compounds have long been known; [2.2]paracyclophane was first reported as a cyclic dimer of paraxylylene by Brown et al. in 1949 [2]. In 1951, Cram et al. reported the practical synthesis of [2.2

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• largest cyclic array in the series. The oxidative fusion reaction with [bis(trifluoroacetoxy)iodo]benzene (PIFA) afforded a cyclophane-type aza[5]helicene-incorporated macrocycle, the structure of which was unambiguously revealed by X-ray diffraction analysis. Its optical properties have been investigated

• in detail. Keywords: cyclophane; fluorescence; heterohelicene; intramolecular oxidative coupling; Introduction Conjugated macrocyclic polyarenes have attracted significant attention due to their stimuli-responsive optoelectronic properties, dynamic structural changes, and host–guest interactions [1

• an aza[5]helicene-incorporated macrocycle. The resulting cyclophane-like structure and its optical properties have been analyzed in detail. Results and Discussion Synthesis and characterization Synthesis We obtained o-phenylene-pyrrole-thiophene hybrid icosamer 4 during our attempt to synthesize

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• engineering redox-switchable chiral luminophores. In 2024, the same research group expanded on this redox-responsive platform by constructing a polycationic open-shell cyclophane 22, comprising carbazole-embedded aza[7]helicene subunits [36]. Compound 22 displays intense fluorescence (ΦF = 0.99

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• such stimuli. When the rotaxane motif contains cyclophane or a crown ether, stimuli induced by a transition metal or an electrostatic interaction have been widely used. These interactions are easily controlled, and they induce relatively strong coordination interactions among the components, making

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• solution. This concept was further developed with a bis-acridinium cyclophane [31] as a multiresponsive receptor for selective phase transfer. In organic media, this macrocyclic receptor presented an affinity for polyaromatic guests with strong selectivity for perylene. A reversible guest release was

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• spectroscopic analysis of the [2]catenanes (18, 20, and 22) revealed various dynamic processes in solution. While circumrotation of the polyether macrocycle around the tetracationic cyclophane was either impossible (for 18 and 20, due to the presence of the sterically demanding BINOL unit) or slow on the NMR

• timescale at room temperature (for 22), the other two dynamic processes, namely circumrotation of the tetracationic cyclophane through the cavity of the polyether and a “rocking motion” of the oxygen–oxygen axis of the hydroquinone units, were fast on the NMR timescale at room temperature. In a follow-up

• and P isomers), similar to (S,S)-5 (see Figure 2). Secondly, the embedding of the DNP unit in the tetracationic cyclophane leads to an element of planar chirality (Rp and Sp isomers). Thus, for each configuration of BINOL, four different diastereoisomers are possible. However, for these specific

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• ]metaparacyclophane and a cyclohexadienone cyclophane. Keywords: cyclophane; metaparacyclophane; nitration; paracyclophane; rearrangement; Introduction Cyclophanes have been described as having bent and battered benzene rings [1] due to a structure that involves one, or more, aromatic rings linked by aliphatic

• chains at non-adjacent carbon positions. Their constrained three-dimensional shapes enforce unusual conformations and interactions between the aromatic decks, all of which results in their unique properties [2][3][4][5]. The most studied cyclophane is [2.2]paracyclophane (1, Figure 1). Not only is it the

• archetypal cyclophane, with a strong interaction between the two aromatic rings, but it is readily available, being a ‘dimer’ for the polymer parylene [6][7]. Over the last twenty years, there has been a resurgence in interest in this compound as a scaffold for the synthesis of asymmetric catalysts, energy

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• decades, it was shown that enantioenriched 2 may serve as a valuable building block to access more advanced chiral cyclophane ligands and catalysts [3][4][19][20][21][22] and therefore its asymmetric synthesis became an important task [3][4][18][19][20][21][22][23][24][25][26][27]. Several strategies to

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• fundamental hydrogen bonding and electrostatic interactions related to the individual recognition motifs [53]. Another cyclophane macrocycle containing two 1,2,3-triazolium moieties was synthesized by Alcalde and co-workers in a moderate yield [54]. The anion-binding behavior of receptor 11 (Figure 10) was

• helped to increase the ability of complexation of 12 with iodide [56]. 2.7. Functional molecular crystal and materials Combining anion–arene interactions and controlling the electron-transfer or charge-transfer process concerning an anionic guest by using a cyclophane is uncommon [57] but can be realized

• by inserting a photoactive binding motif into a cyclophane [58]. In this regard, Li et al. have synthesized a cationic cyclophane 13 (Figure 11) based on an electron poor naphthalenediimide (NDI) moiety and cationic 1,2,3-triazolium units. Cyclophane 13 was employed to control the interactions

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• cyclophane-type B12 artificial enzyme also mediated similar carbon-skeleton rearrangements [32]. We developed another artificial enzyme composed of human serum albumin (HSA) and heptapropyl cobyrinate [34]. It is known that HSA acts as a carrier for in vivo hydrophobic molecules. Hydrophobic B12 model

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• %). Subsequently, hydrogenation of compounds 126 and 125 was accomplished with H2 under Pd/C catalysis conditions to afford the respective saturated macrocyclic products 127 (80%) and 128 (90%). Since the small ring cyclophane is highly strained, compound 125 was formed as a minor product (Scheme 19). Recently, Li

• coupling approach to Z-stilbene derivative 85. Synthesis of substituted trans-stilbene derivatives via SM coupling and RCM. Synthesis of biaryl derivatives via sequential EM, DA followed by SM coupling. Synthesis of the dibenzocyclooctadiene core of schisandrene. Synthesis of cyclophane 115 via SM coupling

• and RCM as key steps. Synthesis of cyclophane 120 and 122 via SM coupling and RCM as key steps. Synthesis of cyclophanes via SM and RCM. Synthesis of MK-6325 (141) via RCM and SM coupling. Acknowledgements We thank the Council of Scientific and Industrial Research (CSIR), New Delhi [02(0272)/16/EMR

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• first TTF-based pseudorotaxane was reported by Stoddart and Williams in 1991 (Figure 5) [33]. At this time, they investigated the host–guest properties of the π-electron-poor cyclophane cyclobis(paraquat-p-phenylene) (3) in form of the tetrakis(hexafluorophosphate) salt [58]. The square-shaped host

• -called “rotacatenane” (Figure 22) [99]. The rotacatenane 24 consists of their previously used rotaxane framework except that the enlarged cyclophane cyclobis(paraquat-4,4′-biphenylene) is used as wheel component. The cavity of this macrocycle is large enough to host two planar molecules in a cofacial

• breakthroughs for the construction of TTF-based supramolecular architectures: (b) Stepwise deprotection/alkylation, (c) phosphite-mediated heterocoupling, and (d) pyrrolo-annulated TTF derivatives I and J. (a) Host–guest equilibrium between π-electron-poor cyclophane 3 and different TTFs with their

From supramolecular chemistry to the nucleosome: studies in biomolecular recognition

• Marcey L. Waters

Beilstein J. Org. Chem. 2016, 12, 1863–1869, doi:10.3762/bjoc.12.175

• interests. (a) Cyclophane receptors from Dennis Dougherty’s group in the late ‘80’s and early ‘90’s that demonstrated cation–π interactions [2]. (b) Cyclophane receptors from the Diederich group in the late ‘80’s and early ‘90’s that demonstrated the “nonclassical hydrophobic effect” [3]. (c) The Hunter

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• kinetic and thermodynamic properties. The nanomolar affinity in water is exceptionally strong for a synthetic cyclophane host molecule, and it is driven by a large favorable change in enthalpy. The two oxygen atoms on the encapsulated squaraine dye form hydrogen bonds to the four macrocycle NH residues

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• benzene ring includes intermediate loss of aromaticity followed by rearomatization during the formation of the cyclophane ring [51]. However, a recently investigated example shows, that breaking the aromatic character of a phenyl ring is not necessary for building up a bended aryl ether in a biological

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• of 2,6-disubstituted pyridine 60 was treated with GI, the expected macrocycle 61 was obtained (51%) together with the dimeric cyclophane 62 (20%). The authors explained that the sulfone moieties facilitated the RCM by steering the alkenyl chains into a favorable conformation, but it also may be

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• ]catenane 6c with the tetracationic cyclophane holding one of the peripheral benzene rings [14]. The TTF unit in 6a and 6b adopted a stable cis or trans configuration, although typically the two configurations easily isomerize into each other in solution. Macrocycle 3 is a brown solid due to the existence

[2.2]Paracyclophane derivatives containing tetrathiafulvalene moieties

• Laura G. Sarbu,
• Lucian G. Bahrin,
• Peter G. Jones,
• Lucian M. Birsa and
• Henning Hopf

Beilstein J. Org. Chem. 2015, 11, 1917–1921, doi:10.3762/bjoc.11.207

• (Figure 1). The molecular dimensions confirm the extensive p–π conjugation within the dithiocarbamate group; the N(1)–C(19) bond length is 1.341(3) Å, some 0.12 Å shorter than N(1)–C(20) and N(1)–C(21), which are essentially σ-bonds. The cyclophane group displays the usual indicators of strain (e.g

• -2-thione group relative to the cyclophane; the torsion angle C3–C4–C17–S3 is −45.9° in the first molecule but −142.4° in the second. CCDC-1412357 contains the supplementary crystallographic data for compound 6 (see also Supporting Information File 1). These data can be obtained free of charge from

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• cyclophane 41b being formed in 23% yield along with 30% of 42b. Diacid 40c returned only the dialkane product 42c probably because the two reaction centers were held too far apart by the rigid p-xylene linker. Some other compound types have proved to be effective donors in SCPC, picking up h+ from the

Design and synthesis of hybrid cyclophanes containing thiophene and indole units via Grignard reaction, Fischer indolization and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Mukesh E. Shirbhate

Beilstein J. Org. Chem. 2015, 11, 1514–1519, doi:10.3762/bjoc.11.165

• via Grignard addition, Fischer indolization and ring-closing metathesis as key steps. Keywords: cyclophane; Grignard reaction; Fischer indolization; ring-closing metathesis; Introduction Modern olefin metathesis catalysts enable a late stage ring-closing step starting with bisolefinic substrates

• cyclophanes the development of powerful and general synthetic methods is highly desirable. Herein, we report a new approach to thiophene- and indole-containing hybrid cyclophane derivatives via Grignard addition, Fischer indolization and RCM as key steps. Strategy The retrosynthetic strategy to the target

• cyclophane 1 containing the thiophene and indole moieties is shown in Figure 1. Here, we conceived thiophene-containing diolefin 3 as a possible synthon to assemble the target molecule 1 via 2. Route A involves an RCM of 3 followed by Fischer indolization of 2 (Figure 1). Alternatively, Fischer indolization

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• , we have included a strategy where the reaction was used for assembling the cyclophane skeleton for further functionalization. In several instances, after the cyclophane is made several popular reactions are used and these are not covered here. We included various natural products related to

• cyclophanes. To keep the length of the review at a manageable level the literature related to orthocyclophanes was not included. Keywords: addition reactions; coupling reactions; cyclophane; metathesis; muscopyridine; name reactions; natural products; Indroduction Cyclophanes [1][2][3][4][5][6][7][8][9][10

• attachment of the alkyl chain to the aromatic system. In this review we are not discussing orthocyclophanes but rather focus on meta- and paracyclophanes only. The aromatic ring present in the cyclophane system can be either heterocyclic or carbocylic in nature. If there is a heteroatom present in the

The preparation of new functionalized [2.2]paracyclophane derivatives with N-containing functional groups

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 437–445, doi:10.3762/bjoc.11.50

• preparation of various cyclophanes bearing substituents with nitrogen-containing functional groups, e.g., the pseudo-ortho diamine 8, the bis secondary amine 23, and the crownophanes 18 and 19. Several of these new cyclophane derivatives (18, 19, 22, 26, 28) have been characterized by X-ray structural

• rings, [Sar]n, n again ranging from 1 to 8. Of course, these two types of substituents will display different reactivities since they are bonded to differently hybridized carbon atoms. In a way, the rigid cyclophane carbon framework may be regarded as a hexadecavalent “superatom” that can bind up to 16

• cyclophane molecule, all pointing in the same direction, a structure results that bears functional groups on the one half of the molecule whereas the other consists of aliphatic and aromatic C–H bonds only. It is very likely that these geometries will have a strong influence on chemical and physical

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• neglected so far. Functional groups in pseudo-geminally substituted [2.2]paracyclophanes often undergo highly specific reactions. This is due to the rigid framework and the short distance between the two aromatic rings within the [2.2]paracyclophane unit. Thus, unsaturated cyclophane bis(esters) undergo

• :1.4. It is interesting to note that the synthesis of the [2.3.2](1,2,4)cyclophane derivative 5 has been previously reported as the result of bromine addition to bis(acetylene) 1, in 87% yield [13]. In both experiments, the formation of elemental red selenium was observed. The unexpected reaction

• dichloride or selenium dibromide, we isolated only the [2.3.2](1,2,4)cyclophane derivatives 2, 3 and 5, 6, respectively; no traces of tetrahalides 4 and 7 were detected (Table 1, entries 2 and 4). Although unexpected, the lack of tetrahalides from these experiments proved later to be of significant

Five-membered ring annelation in [2.2]paracyclophanes by aldol condensation

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2014, 10, 2021–2026, doi:10.3762/bjoc.10.210

• in the past on numerous cyclophane derivatives bearing condensed four- to seven-membered rings, as shown by the representative examples of 1 (E = CO2CH3) [2], 2 [3], 3 [4], and 4 [5]. Many of these compounds possess interesting structural and spectroscopic properties, and can be used as substrates

• of the cyclophane framework (endo-orientation) or to the outer section of the derivative (exo-orientation). Thus altogether the six different diastereomers 10–15 result. Results and Discussion As the experiment shows (treatment of 9 with either sodium hydroxide in methanol or aniline in methanol

• cyclophane core. In other words, the oxygen atom faces a methylene hydrogen atom of the bridge. In principle the alternative orientation is also possible, with the methyl substituent taking this position. A comparable situation has been observed for the 4-acetyl derivative of [2.2]paracyclophane, with the

Building complex carbon skeletons with ethynyl[2.2]paracyclophanes

• Ina Dix,
• Lidija Bondarenko,
• Peter G. Jones,
• Thomas Oeser and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 2013–2020, doi:10.3762/bjoc.10.209

• extensive column chromatography/recrystallization. Isomer 11 is chiral and could be separated on a column impregnated with cellulose tris(3,5-dimethylphenyl)carbamate. The bridge-extended cyclophane precursor 18 furnished the ring-enlarged cyclophanes 19 and 20 on Glaser–Hay coupling. Cross-coupling of 4

• 12 displays the “parallel” geometry of the extra bridges, and the two paracyclophane units are indeed exactly parallel to each other by symmetry. The cyclophane rings of the asymmetric unit are twisted by 8.4°. The extra bridges are again bowed, and the angles depart slightly more from 180° (167° at

• (r.m.s.d. 0.12 Å). The bridges are “parallel”, although the angle between the two cyclophane units is ca. 16° (the average of the interplanar angles between the two halves across the pseudo-mirror plane). The two paracyclophane units each show the usual patterns of strain; the twist angles are 1.4 and 4.4