Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -substituted indoles. The authors also tried the reaction with C3-substituted indoles to functionalize the C2 position. However, a very low enantioselectivity was achieved in the latter case (Scheme 10) [35]. Lin and co-workers designed a planar chiral phosphoric acid containing a [2.2]paracyclophane moiety

• using Nps-iminophosphonates as electrophiles. Aza-Friedel–Crafts reaction between indole and α-iminophosphonate. [2.2]-Paracyclophane-derived chiral phosphoric acids as catalyst. Aza-Friedel–Crafts reaction through ring opening of sulfamidates. Isoquinoline-1,3(2H,4H)-dione scaffolds as electrophiles

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• characterized as an oxa[1.7]meta-paracyclophane framework. In the literature we can find reports about the isolation/synthesis of combretastatins D and their analogues which showed different biological activities, e.g., antineoplastic, anti-inflammatory, and α-glucosidase inhibition [13][14][15]. The presence

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• Waser employed an isothiourea catalyst for esterification-mediated kinetic resolution of paracyclophane derivatives with planar chirality [19]. Parida and Pan showed that a Michael reaction coupled with an acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones can produce a

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

• undoubtedly the result of the lengthy syntheses of these compounds. We report the simple synthesis of a rare example of a non-symmetric [2.2]metaparacyclophane. Treatment of [2.2]paracyclophane under standard nitration conditions gives a mixture of 4-nitro[2.2]paracyclophane, 4-hydroxy-5-nitro[2.2

• ]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

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

• David Weinzierl Mario Waser Institute of Organic Chemistry, Johannes Kepler University Linz, Altenbergerstrasse 69, 4040 Linz, Austria 10.3762/bjoc.17.68 Abstract We herein report a method for the kinetic resolution of racemic 4-hydroxy[2.2]paracyclophane by means of a chiral isothiourea

• ; planar chirality; Introduction Substituted [2.2]paracyclophanes are fascinating planar chiral molecules [1][2][3][4][5][6][7][8][9][10][11][12] which have been systematically investigated since Brown and Farthing discovered the formation of the unsubstituted and achiral parent [2.2]paracyclophane (1

• out kinetic resolutions of easily accessed racemic precursors [3][4][13][14][15]. 4-Hydroxy[2.2]paracyclophane (2) is one of the commonly used building blocks, which is easily accessible in a racemic manner starting from 1 according to nowadays well-established procedures [16][17][18]. Over the last

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• significantly. However, with the aniline derivative 69 (R = Ph on nitrogen), the ee dropped precipitously (Scheme 15). Chen et al. used a paracyclophane-based NHC ligand, along with Cu2O, to perform similar asymmetric 1,2-silyl additions onto activated imines. For several substrates (47) studied, the chemical

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• contain functional groups which can also be modified. Jiang et al. [108] attached a pyridyl moiety to a [2.2]paracyclophane phosphine support via a nucleophilic substitution reaction (Scheme 25). The nucleophile was generated by the addition of n-BuLi to enantiomerically pure [2.2]paracyclophane 129

• planar chiral P,N-paracyclophane phosphine ligand 132 with a relatively low yield (42%). The [2.2]paracyclophane has proved to be an important support for planar chiral phosphine ligands. The ligands are generally rigid crystalline compounds that are stable in both high and low pH media and thermally

• 102. Synthesis of pyrrolylphosphine ligands. Synthesis of phosphine guanidinium ligands. Synthesis of a polydentate aminophosphine ligand. Synthesis of quinolylphosphine ligands. Synthesis of N-(triazolylmethyl)phosphanamine ligands. Synthesis of oxazaphosphorines. Synthesis of paracyclophane

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• capsule 40 formed through hydrogen-bonding and the cavity was found to be able to encapsulate different organic molecules such as alkanes, acids, amines, etc. The encapsulation of a [2.2]paracyclophane in the cage was achieved by ball milling at 30 Hz (Figure 22) and the host–guest product 40 was verified

• reaction through solid-state grinding. Hydrogen-bond donors are a) resorcinol and b) 1,8-dipyridylnaphthalene, respectively. Formation of the cage and encapsulation of [2.2]paracyclophane guest molecule in the cage was done simultaneously under mechanochemical conditions. Formation of the 1:1 complex C60

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• Donghui Pan Yanbin Wang Guomin Xiao School of Chemistry and Chemical Engineering, Southeast University, 2 Dongnan Daxue Road, Nanjing, Jiangsu, 211189, P. R. China 10.3762/bjoc.12.237 Abstract We report a green and convenient protocol to prepare 4,7,12,15-tetrachloro[2.2]paracyclophane, the

• sodium hydroxide solution instead of silver oxide for anion exchange, results in a significant improvement in product yield. Furthermore, four substituted [2.2]paracyclophanes were also prepared in this convenient way. Keywords: bromination; dimerization; H2O2–HBr system; paracyclophane; polymerization

• commercialized, and its precursor [2.2]paracyclophane (Figure 2) was typically produced by Hofmann elimination [5][6]. As reported, the uniform coating properties of parylene films were improved by introducing halogen atoms to the structure of the parent [2.2]paracyclophane [7]. Therefore, the two chloride atoms

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• spirooxindoles utilizing the hydroxy group and the unsaturated ketone moiety. Song and co-workers designed a novel [2.2]paracyclophane-based thiourea catalyst (cat. 25), which was successfully applied to the enantioselective aldol reaction of isatins with enolizable ketones using H2O as the additive. The desired

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

• usually requires sophisticated chemistry in organic laboratories. Prominent examples are [n]paracyclophane moieties in natural products such as haouamines [48] or fijiolides [49][50]. As for the [7]paracyclophane in haouamine A and B, a reasonable suggestion for compensating the high barrier of a bended

• scaffold. In this study, 13C- and 18O-labeled L-tyrosine was used to elucidate the biosynthesis of pyrrocidines such as pyrrocidine A (24, Scheme 6) bearing a [9]paracyclophane moiety in the fungus Acremonium zeae [52]. Compound 24 is the product of a mixed PKS and NRPS machinery containing nine acetate

• phenolic oxygen is conserved here. To distinguish between these mechanisms, (4’-hydroxy-18O,1-13C)-L-tyrosine was enantioselectively synthesized and fed to A. zeae. Both labels were incorporated into 24, thus providing evidence for mechanism B and a paracyclophane formation without intermediate loss of

[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

• of Inorganic and Analytical Chemistry, Technical University of Braunschweig, Hagenring 30, D-38106 Braunschweig 10.3762/bjoc.11.207 Abstract The synthesis of [2.2]paracyclophane derivatives containing tetrathiafulvalene units has been accomplished by the coupling reaction of 4-([2.2]paracyclophan-4

• -yl)-1,3-dithiol-2-thione in the presence of trimethylphosphite. The 1,3-dithiol-2-thione derivative was in turn synthesized by the regioselective bromination of 4-acetyl[2.2]paracyclophane, then through the corresponding dithiocarbamates and 1,3-dithiolium salts. Keywords: dithiocarbamates; 1,3

• -dithiolium salts; [2.2]paracyclophane; regioselective bromination; stereoisomers; tetrathiafulvalenes; Introduction Tetrathiafulvalene (TTF) and its derivatives have been extensively studied with respect to their applications as organic metals and superconductors [1][2]. These properties are a consequence

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

• to a large number of cations, anions, and neutral molecules. Cyclophanes are widely used in materials science and molecular recognition processes [48][49][50][51][52]. A general classification of cyclophanes is as follows: [n]orthocyclophane, [n]metacyclophane, and [n]paracyclophane (1–3) (Figure 1

• -workers have synthesized donut-shaped cyclophanes 55 and 56 by using the Glaser–Eglinton coupling as a key step (Figure 6) [94]. Morisaki and co-workers [95] have synthesized 4,7,12,15-tetrasubstituted [2.2]paracyclophane 57 and further studies were carried out to find out the properties of these

• synthesis of polyunsaturated [10]paracyclophane annulated by two azulene rings by using the McMurry reaction [100][101]. The bis(trimethylsilyl)enol ether 74 was reacted with 3-methoxycarbonyl-2H-cyclohepta[b]furan-2-one (75) in refluxing decaline to generate the 1,4-diazulenobenzene derivative 76. Double

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

• -38106 Braunschweig, Germany, Fax: (+49)531-391-5387 10.3762/bjoc.11.50 Abstract The two isomeric bis(isocyanates) 4,12- and 4,16-di-isocyanato[2.2]paracyclophane, 16 and 28, have been prepared from their corresponding diacids by simple routes. The two isomers are versatile intermediates for the

• analysis. Keywords: azides; crownophanes; cyclophanes; isocyanates; stereochemistry; X-ray analysis; Introduction Although hundreds of mono- und disubstituted derivatives of [2.2]paracyclophane [3][4] have been described since its initial preparation [5], relatively little is known about more highly

• -geminally disubstituted derivative in which the two (identical or non-identical) substituents are directly above/below each other (see below). To the best of our knowledge the first fully functionalized [2.2]paracyclophane was the fluorocarbon perfluoro[2.2]paracyclophane (2) first prepared by Dolbier and

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

• substructure. The reactions have been found to be sensitive to the substitution of the ethynyl group. The formation of dienes with a zig-zag configuration is related to that observed for non-conjugated cyclic diynes of medium ring size. Keywords: acetylenes; dienes; [2.2]paracyclophane; selenium halides

• ; Introduction Starting with their discovery in 1949, the [2.2]paracyclophane molecule and its derivatives have been intensely studied [1][2][3]. Of particular interest are the geometry and transannular interactions of these molecules, the study of electrophilic aromatic substitution reactions involving these

• 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

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

• -38106 Braunschweig, Germany 10.3762/bjoc.10.210 Abstract Under basic conditions 4,5,12,13-tetraacetyl[2.2]paracyclophane (9) cyclizes by a double aldol condensation to provide the two aldols 12 and 15 in a 3:7 ratio. The structures of these compounds were obtained from X-ray structural analysis

• , spectroscopic data, and mechanistic considerations. On acid treatment 12 is dehydrated to a mixture of the condensed five-membered [2.2]paracyclophane derivatives 18–20, whereas 15 yields a mixture of the isomeric cyclopentadienones 21–23. The structures of these elimination products are also deduced from X-ray

• -ray analysis of its deuteriochloroform solvate. The asymmetric unit is shown in Figure 1. The structure of 12 displays approximate C2 symmetry, with a r.m.s. deviation of 0.05 Å. It shows the normal distortions associated with the [2.2]paracyclophane geometry, with lengthened bridge bonds, widened sp3

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

• moieties are anchored in para-position, 5, the lower oligomers can no longer be cyclic because they would be too highly strained. When two ethynyl groups are placed into the benzene rings of [2.2]paracyclophane, the situation changes. In a strict sense the analog of 1,2-diethynylbenzene (1) is 4,5

• -diethynyl[2.2]paracyclophane, i.e., the hydrocarbon with two ethynyl groups in vicinal position in the same ring [2][3]. If, however, our target molecules are to have the two triple bonds in different benzene rings, the pseudo-gem-diethynyl[2.2]paracyclophane 2 is the analog of 1 (Scheme 1). Analogously

• structural information. Our proposal of two types of dimers results, firstly, from the spectra of the dimers generated by Glaser coupling of 4-ethynyl[2.2]paracyclophane and secondly, from the dimerization results with the pseudo-ortho compound 4 described below. NMR analysis proved unambiguously that two

Synthesis and structure of trans-bis(1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene)palladium(II) dichloride and diacetate. Suzuki–Miyaura coupling of polybromoarenes with high catalytic turnover efficiencies

• Jeelani Basha Shaik,
• Venkatachalam Ramkumar,
• Babu Varghese and
• Sethuraman Sankararaman

Beilstein J. Org. Chem. 2013, 9, 698–704, doi:10.3762/bjoc.9.79

• -4,5,9,10-tetrabromopyrene (21) and 4,7,12,15-tetrabromo[2.2]paracyclophane (26) [29] are particularly difficult substrates to undergo Suzuki–Miyaura coupling in the presence of conventional catalysts such as PdCl2(PPh3)2, Pd(PPh3)4 and Pd(dba)2. The coupling of 4,7,12,15-tetrabromo[2.2]paracyclophane (26

• ) with phenylmagnesium bromide in the presence of a NiCl2(PPh3)2 catalyst has been reported to yield 4,7,12,15-tetraphenyl[2.2]paracyclophane (27) in only 6% [29]. In the present study these substrates underwent four-fold Suzuki–Miyaura coupling smoothly resulting in the formation of fully substituted

• polychloroarenes did not give a clean reaction, and the reactions were sluggish in comparison to polybromoarenes. In addition, unlike the polybromo derivatives, the polychloroarene derivatives of pyrene, triphenylene and [2,2]paracyclophane are not readily available. Conclusion In conclusion, the dichloro complex

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• PPY (56). In the first case (368) the paracyclophane substituent leads to a lower affinity towards the acetyl cation. The two Lewis bases 371 and 372 show almost no influence of the paracyclophane moiety on the ACA values. Inclusion of an amide substituent as in pyridine 380 leads to a surprisingly

Synthesis of new pyrrole–pyridine-based ligands using an in situ Suzuki coupling method

• Matthias Böttger,
• Björn Wiegmann,
• Steffen Schaumburg,
• Peter G. Jones,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2012, 8, 1037–1047, doi:10.3762/bjoc.8.116

• [2.2]paracyclophane-derivatives [11]. This comprised the in situ reaction of the freshly prepared boronic acid/ester with the heteroaryl bromides 8–10. These starting compounds could be prepared by using literature procedures, as shown in Scheme 4. Substance 8 was synthesized by following the standard

Intraannular photoreactions in pseudo-geminally substituted [2.2]paracyclophanes

• Henning Hopf,
• Vitaly Raev and
• Peter G. Jones

Beilstein J. Org. Chem. 2011, 7, 658–667, doi:10.3762/bjoc.7.78

• Braunschweig, Germany, Fax: +49 531 / 391 5387 10.3762/bjoc.7.78 Abstract The photoisomerization of the pseudo-geminal tetraene 11 furnishes the cyclooctadiene derivatives 13 and 15 with a completely new type of molecular bridge for a [2.2]paracyclophane which promise many interesting novel applications; the

• reaction. One such system is the generalized paracyclophane molecule 1 shown in Scheme 1. Here the distance between the benzene “decks” carrying the functional groups F1 and F2 can be adjusted both by the length of the two molecular bridges (variation of m and n), and by the relative orientation between

• same type. In our work we have so far concentrated our efforts on derivatives of [2.2]paracyclophane (1, m = n = 2) with the two functional groups usually in the so-called pseudo-geminal positions, that is, directly above each other as shown in 2. The intraannular distance is approximately 3.1 Å in

Preparation and NMR spectra of four isomeric diformyl[2.2]paracyclophanes (cyclophanes 66)

• Ina Dix,
• Henning Hopf,
• Thota B. N. Satyanarayana and
• Ludger Ernst

Beilstein J. Org. Chem. 2010, 6, 932–937, doi:10.3762/bjoc.6.104

• Previously, we reported that the [2 + 4] cycloaddition of 1,2,4,5-hexatetraene (1) to propiolic aldehyde (2) produced a mixture of four [2.2]paracyclophane dialdehydes 4. This result is in agreement with the generation of the p-xylylene intermediate 3 in the first step of the reaction, which can dimerize by

• and can decompose, even under refrigeration. Although we have separated the four isomers and used them many times for the preparation of numerous [2.2]paracyclophane derivatives (inter alia annelated derivatives [2], metal complexes [3][4][5], diethynyl derivatives [6][7] and preparation of ligands

• of all isomers and may hence be easily separated. NMR spectra of the diformyl[2.2]paracyclophanes 4 As the 1H and 13C NMR spectra of [2.2]paracyclophane-4-carbaldehyde have previously been fully assigned and, hence, the influence of the substituent upon the 1H and 13C NMR chemical shifts of all

Reversible intramolecular photocycloaddition of a bis(9-anthrylbutadienyl)paracyclophane – an inverse photochromic system. (Photoactive cyclophanes 5)

• Henning Hopf,
• Christian Beck,
• Jean-Pierre Desvergne,
• Henri Bouas-Laurent,
• Peter G. Jones and
• Ludger Ernst

Beilstein J. Org. Chem. 2009, 5, No. 20, doi:10.3762/bjoc.5.20

• -anthracenyl)buta-1,3-dienyl][2.2]paracyclophane (2), prepared in 35% overall yield from [2.2]paracyclophane, absorbs light at λmax = 400 nm with a tail down to 480 nm. By irradiation into this band, 2 generates a single photoproduct, 4, whose absorption maximum is situated at 306 nm. The starting material is

• unprecedented. Summary and Conclusion The target molecule (dianthryl-butadienyl[2.2]paracyclophane 2) was synthesized and shown to possess the anticipated photochromic properties. The two interconverting forms exhibit good thermal stability. The cycloreversion can be induced by irradiation or by heating

• of oxygen with an argon or nitrogen stream. Preparations 1. 4,13-bis[(1E,3E)-4-(9-anthracenyl)-buta-1,3-dienyl][2.2]paracyclophane (2): In a 250 mL, dried round-bottom flask, equipped with a reflux condenser, a Claisen adapter, a stirring system, and degassed with nitrogen, 1.3 g dialdehyde (4.1 mmol

Enantiospecific synthesis of [2.2]paracyclophane- 4-thiol and derivatives

• Gareth J. Rowlands and
• Richard J. Seacome

Beilstein J. Org. Chem. 2009, 5, No. 9, doi:10.3762/bjoc.5.9

• describes a simple route to enantiomerically enriched [2.2]paracyclophane-4-thiol via the stereospecific introduction of a chiral sulfoxide to the [2.2]paracyclophane skeleton. The first synthesis of an enantiomerically enriched planar chiral benzothiazole is also reported. Keywords: heterocycle; [2.2

• ]paracyclophane; resolution; sulfur; Introduction [2.2]Paracyclophane (1; R = H) is a fascinating compound comprising of two eclipsing benzene rings that are held in place by two ethyl bridges at the para positions (Figure 1). The close proximity of the arene moieties results in strong electronic and structural

• interactions between the two rings and between substituents appended to each layer [1][2]. The resulting unique properties have led to derivatives of [2.2]paracyclophane being employed in a wide range of disciplines including polymer, material and electronic chemistry [3][4][5][6][7][8][9]. Whilst