1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• ]. In tripodal molecules, three functional arms are bound to a central trivalent scaffold, which can be a single atom (e.g., carbon, nitrogen, or phosphorus), a small ring (usually aromatic or saturated six-membered ring), or a macrocycle (Figure 1a). The functional properties of tripodal molecules are

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• ]. Jones et al. designed a cyclooctene-based Co–salen macrocycle catalyst for the phenolic KR of epichlorohydrin and 1,2-epoxyhexane [21]. However, these Co–salen systems suffer from several limitations such as tedious preparation of salen scaffolds, excess use of epoxides, high catalyst loadings, narrow

Synthesis of meso-pyrrole-substituted corroles by condensation of 1,9-diformyldipyrromethanes with pyrrole

• Baris Temelli and
• Pinar Kapci

Beilstein J. Org. Chem. 2022, 18, 1403–1409, doi:10.3762/bjoc.18.145

• porphyrins, are tetrapyrrolic aromatic compounds, with the lack of one meso-carbon atom on the macrocycle [1][2][3][4]. This feature supplies a smaller ring cavity than in the case of porphyrins, three NH in the core, and coordination ability with high-valence transition metal ions. It is noteworthy that

• in Figure 1. As expected, pyrrole C4, C3, C5 and NH protons appeared at 6.51, 7.05, 7.27 and 8.90 ppm, respectively. Coupling of all pyrrole protons can be seen in the 1H,1H-COSY NMR spectrum (Supporting Information File 1, Figure S3). The β-protons of the corrole macrocycle and the phenyl group gave

• complexes of A2B-type pyrrole substituted corroles. We believe that the placement of the polymerizable pyrrole as a conjugated substituent to the macrocycle is an important contribution to the polymerization of corroles and the expansion of the usage areas of these compounds. Further studies on the

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• main GGPP cyclization products, along with two minor compounds, namely the isoelisabethatrienes (IEs) A (13%) and B (9%), respectively. Interestingly, the elisabethatriene diterpene macrocycle and its isoforms can act as biosynthetic precursors of the bioactive compounds erogorgiaene and pseudopterosin

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• ]. Therefore, Roberge, Fogg, and co-workers investigated the advantages of continuously stirred tank reactors (CSTR) and tube reactors in comparison to the corresponding batch reaction for the ring-closing metathesis of diene 58, producing macrocyclic olefin 60 (Scheme 14) [52]. Although, macrocycle 60 is not

• and with a Z-selectivity of >98% [54]. In contrast, Amorelli, Collins, and co-workers performed a ring-closing metathesis for the synthesis of macrocycle 72 from diene 70 at high temperatures of 150 °C in only 5 min without removal of formed ethylene (Scheme 17) [55]. Under these conditions, the

• employed Stewart–Grubbs catalyst 71 is completely decomposed but its decomposition products could efficiently be removed by passing the reaction mixture through a cartridge containing a mixture of silica and charcoal providing 72 in 32% yield at a productivity of 0.2 g/h. The macrocycle 72 was already

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• trans-styrylboronic acid (43, Figure 10). The catalytic reaction inside the chiral cavity of (S)-40 provided a yield up to 91% with a very high enantioselectivity (94% ee). In contrast, the larger chiral macrocycle (S)-41 afforded a slightly lower catalytic activity (87%), however, at a similar

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

• ][36][37][38], anion templates [39][40], ammonium crown ether templates [41], and templates based on π–π interactions [42]. In 2004, Sauvage and co-workers have used a Cu(I)-based passive metal template approach to synthesize a [2]catenane containing an optically pure BINOL unit in each macrocycle [43

• ]. The template complex (S)-3 was assembled by mixing the macrocycle (S)-1 (containing both a phenanthroline ligand and a BINOL unit) with [Cu(CH3CN4)]PF6 and the acyclic phenanthroline precursor 2. Then, the BINOL-based diiodide (S)-4 and Cs2CO3 were added successively over 18 hours. This resulted in

• treated with copper iodide to obtain the phenanthroline–Cu(I) complex (R)-8. A Glaser-type coupling with the terminal alkynes 9, followed by demetalation, proceeds smoothly in 78% yield. This furnishes the desired chiral rotaxane (R)-10, consisting of a BINOL-based macrocycle and a diyne thread. The CD

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• readily incorporated by both homo and hetero [1 + 1] macrocyclic condensation of bisamine and bisisothiocyanate fragments. With the easy synthesis, gram-scale of macrocycle products can be readily obtained. These chiral macrocycles were applied in catalyzing bioinspired decarboxylative Mannich reactions

• . Only 5 mol % of the optimal macrocycle catalyst efficiently catalyzed the decarboxylative addition of a broad scope of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. The rigid macrocyclic framework and the cooperation between the thiourea and

• catalytic conditions. On the other hand, the covalently pendant catalytic group may reside far away from the center of the cavity. On the other hand, we envisaged by use of tailored building units already containing definite catalytic sites to directly form a macrocycle scaffold could provide a different

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• ]. This occurs via strong steric interactions, often outside the macrocycle (Figure 1a) [11], that affect the first coordination sphere of the metal or by creating a spatial confinement around the metal that is thus directed towards the inner cavity (Figure 1b) [26][27]. Contrarily, calix[6]arene

• macrocycles are less exploited in catalysis [28]. The larger macrocycle size, its conformational adaptability, and the possibility to selectively functionalize the macrocycle offered several opportunities to design synthetic receptors and prototypes of nanodevices, instead [29]. In this context, we recently

• gold(I) nuclei to the opposite sides of the macrocycle, offering them the possibility to approach the cavity, thus exerting any control over the catalytic manifold (Figure 1d). Results and Discussion Synthesis and characterization The synthesis of novel macrocyclic calix[6]arene ligands was first

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• dioxane gave the crude ammonium salt, which was subjected to biphasic ring closure; the hydrochloride salt was added dropwise to a stirred emulsion of saturated NaHCO3 solution in chloroform [55]. Macrocycle 11 was obtained in acceptable yield as a diastereomeric mixture (dr 87:13), but the diastereomers

• NMR spectra. The solubility issues forced us to investigate also other modification protocols. Thus, macrocycle 11 was subjected to an ozonolysis with subsequent Wittig reaction in a one-pot manner (Scheme 4). Performing the ozonolysis in presence of pyridine led to immediate reduction of the primary

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• macrocycle and of the Lys–His bond, which is part of the cross-link, is prevented by the stapling (Figure 3 and Supporting Information File 1, Figures S8 to S10). Conformational analysis The identification of two isomers of P5 by LC–MS led us investigate the possibility of diastereomers and conformers in the

• macrocycle. The amide bond in the staple of P5 is connected to two flexible aliphatic chains and may exist in cis and trans configuration. The energy difference in the analogue N-methylacetamide (NMA) favours the trans isomer by about 2.3 kcal mol−1, which corresponds to an expected cis/trans ratio of about

• 1:44 at 300 K, with an interconversion barrier of 18.7 kcal mol−1 [83]. The experimental P5.1/P5.2 ratio is nearly 1:3, suggesting an energy difference of only 0.9 kcal mol−1 in favour of P5.2. Strain in the macrocycle might be responsible for such slight decrease in the relative energy between the

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• hemicucurbituril-based macrocycle, alternately consisting of amidobenzene and 2-imidazolidione moieties was designed and synthesized. Based on the fragment coupling strategy, nitrobenzene-containing hemicucurbituril was firstly prepared facilely under alkaline environment, and reduction of the nitro groups

• produced the desired amidobenzene-containing hemicucurbituril. As an original fluorescent chemosensor, it exhibited strong interactions with Fe3+ over other metal cations. The experimental evidence of fluorescence spectra suggested that a 1:1 complex was formed between this macrocycle and Fe3+ with an

• association constant up to (2.1 ± 0.3) × 104 M−1. Meanwhile, this macrocycle showed no obvious or only slight enhancement of the fluorescence intensity with selected anions. Keywords: amidobenzene-containing macrocycle; hemicucurbituril; host–guest interaction; macrocycle; modification; Introduction

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• macrocycle 81 (Scheme 17a) [78]. Compared to bis-thiourea 80, the higher rigidity in the macrocycle 81 not only enforces halide abstraction significantly, but also allowed for a better control of the stereoselectivity in the glycosylation of glycosyl halides 78 with a variety of coupling partners. In this

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• -contained structural discussion [24]. However, with all the advances made in the crystal engineering of planar porphyrins, investigation through exploration into the effect of meso-halogenation on the macrocycle architecture have, to date, not been carried out. Herein we present a comparative analysis of

• porphyrin conformation are observed due to the metal center insertion. The first of these is the stacking between the porphyrin rings (at 3.581(3) Å), which now features the bromine atoms pointing in opposite directions with a ruffled conformation of the porphyrin macrocycle (Figure 3A). Moreover, a similar

• motif of bromine atoms pointing towards the phenyl rings is visible in this structure and seems to be a staple of this series (Figure 3B). Secondly, the edge-on interaction in this structure has changed, where the pyrrole moiety is pointing towards the face of the porphyrin macrocycle as seen in Figure

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• -dependent selective arrangement of one or two substrates within the cavity for photocatalysis. Therefore, this review will focus on: i) the role of the supramolecular system in mediating the photocatalytic selectivity, yield, and the rate of the photocatalytic products and ii) macrocycle-assisted hybrid

• can easily gain information on host–guest interactions in supramolecular systems as well as the photocatalytic reaction efficiency. Review Macrocycle-promoted photocatalysis Photocatalysis based on crown ethers and crown ether derivatives CEs are a class of macrocycles that consist of a ring with a

• on pillararene is a relatively new field, and only a few examples have been reported [53][54]. Wen and co-workers reported the selective photocatalytic oxidation of sulfides in the presence of conjugated macrocycle polymers (COP) with pillar[5]arene struts (Figure 17) [55]. The host–guest

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• synthetic intermediate as the presence of the allyl groups immobilizes the required conformation and at the same time enables the potential incorporation of the macrocycle into a polymeric matrix. Consequently, the subsequent reduction step was carried out in two alternative ways: (i) exclusive reduction of

• chain of calixarene molecules joined together by intermolecular hydrogen bonds between the ureido groups (the C=O···H–N distances were 2.293 and 2.048 Å). One of the ureido functions in the macrocycle also held acetone via a C=O···H–N hydrogen bond (2.085 Å) and via a C=O···H–C bond (2.670 Å) from the

• immobilised in the 1,3-alternate conformation resulted in a macrocycle with a preorganised ureido cavity bearing chiral alkyl substituents in the near proximity. As shown by 1H NMR titration experiments, these compounds function as receptors for chiral anions in DMSO-d6. The chiral recognition ability can

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• corresponding free macrocycle. The detailed understanding of the thermodynamic and electrochemical properties of the tailor-made crown ethers lays the foundation for the construction of new types of molecular redox switches with emergent properties. Keywords: crown ether; isothermal titration calorimetry

• -functionalized crown ether as for the TTF crown ethers, where the NDI unit is in a position more remote from the crown ether binding site. Yet, keeping the formal C2-symmetry of the macrocycle is important to avoid mixtures of isomers upon the threading of directional axles, such as A1·PF6 (Figure 1c) [40

• Information File 1). Slow diffusion of CH3CN into a concentrated solution of NDIC7 in CH2Cl2 yielded single crystals suitable for X-ray diffraction (Figure 2b). The macrocycle displays a folded conformation in the solid state due to the flexible linker, featuring an intramolecular NDI/naphthalene stacking

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• adds more hydrophobic interactions with the aromatic side walls of the bowl-shaped calixarene core. A similar, but even more pronounced trend, is observed for the pumpkin-shaped macrocycle cucurbit[7]uril, favoring the trimethylated over unmethylated lysine by a factor of 3500 [49]. Methylated lysines

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• multiple guests in order to systematically explore the lower size limits of trefoil knots. For example, if TLC were successful with host 1 and guest 2, then a 73 backbone-atom trefoil (and the corresponding unknotted macrocycle) would be formed (Figure 3 and Scheme S1 in Supporting Information File 1

• ), whereas host 1 and guest 3 would lead to a 75 backbone-atom trefoil (and unknotted macrocycle). Results and Discussion The synthesis of bis-macrocyclic host 1 began by breaking the symmetry of naphthalene-1,5-diol (4) by alkylation of one of the alcohols with 2-azidoethyl mesylate to yield azide 5 in 27

• spectrum showed the loss of the ethyl ester peaks (Scheme 4). Bis-macrocyclization of 15 under high-dilution using Shiina’s mixed-anhydride method [29] afforded host 1 in 28% yield. As with the analogous first-generation knot-precursor bis-macrocycle [15], host 1 was formed as a mixture of meta- and ortho

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• example, a carbazole-urea macrocycle was reported previously [10], however, the binding of anions occurred outside the receptor due to modest dimensions of the macrocyclic cavity. Using click-chemistry, a carbazole-triazole macrocycle, “tricarb”, was prepared that showed the ability to form non-covalent

• superstructures [11]. The rings should be of remarkable size for accommodating even small anions, such as acetate. In many cases the receptor is formally a macrocycle, but the anion is bound on its “surface”, not inside the ring [10][12]. A well-known example is the calix[4]pyrrole family, which emerged as an

• “cyanostar” macrocycle [15][16]. Although not a macrocycle, a successful binding motif that is noteworthy for its ability to bind carboxylates in polar environments, is the guanidiniocarbonylpyrrole (GCP) moiety designed by Carsten Schmuck and Michael Schwegmann [17]. The transition from complexation studies

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• of Bordeaux, Pessac, France 10.3762/bjoc.16.128 Abstract The templated clipping of a ferrocene-grafted isophthalic acid derivative to encircle a hydrogen-bonding axle through the reaction with 1,4-bis(aminomethyl)benzene is described. The constituent electroactive macrocycle of the resultant [2

• crystal X-ray structure of a doubly ferrocene-decorated [2]rotaxane are further reported. Keywords: ferrocene; macrocycle; rotaxane; single crystal X-ray structure; template; Introduction The development of interlocked molecules with tailored properties allowed the preparation of molecular machines able

• act as stimuli-responsive molecular “shuttles” with potential applications to prepare nanoscale devices for computing and biomimetic engineering [2][3]. The highly efficient rotaxane formation developed by Leigh allowed the generation of a tetraamide macrocycle on a fumaramide or succinamide thread in

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• molecule. In this structure, it should be noted that there is a high degree of π-stacking between the porphyrin macrocycle. This is highlighted in Figure 4; however, there is a clear preference for the homo-metallic selective interactions between the porphyrin rings. As such, in the crystal packing the Ni

• minor disorder are omitted for clarity (thermal displacement 50%). Porphyrin macrocycle mean-planes are indicated by maroon shading. UV–vis of symmetric and unsymmetric triptycene porphyrin dimers 9 and 16, and the triptycene porphyrin monomer 14 in CHCl3. Emission spectrum of symmetric and unsymmetric

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• side-chain hydroxylation modifications (series iii), with macrocycle ring-size variations (series iv), and with macrocycle homodimerization (series v). We systematically screened the ring-open and ring-closed photoforms of all 29 compounds in vitro, using a range of cellular toxicity assays (against

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• cyclization reaction yielding the corresponding azobenzene 1f was performed using a Cu(I) catalyst generated in situ [36]. Finally, the esters were hydrolyzed under mild conditions resulting in the azobenzene-BAPTA macrocycle 1. To gain some insight into the possible structures of the 1E and 1Z chelators and

• +, giving rise to a highly fluorescent species upon excitation at 485 nm. The fluorescence is greatly diminished after the addition of 10 equivalents of 1E, as the azobenzene macrocycle abstracts the Ca2+ ion from fluorophore 3. Upon irradiation of the ensemble at 365 nm at these low concentrations, a small