Calix[n]arenes represent a very attractive family of macrocyclic compounds with many potential supramolecular applications. Due to their well-established chemistry and many different synthetic strategies, enabling practically any derivatization of the basic skeleton, calixarenes are among the very popular building blocks used for the design and construction of various receptors, sensors and other sophisticated supramolecular systems. Regio- and/or stereo-selective derivatization of calixarenes currently represents a very extensive set of reactions, the overview of which would fill many thick books. Therefore, this review deals with only a small part of the above-mentioned reactions, specifically describes possible ways of bridging the upper rim of calixarenes, often leading to interesting rigidified structures, and also briefly mentions the potential use of these compounds.

Department of Organic Chemistry University of Chemistry and Technology Prague Technická 5 166 28 Prague 6 Czech Republic

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Gutsche C. D., Calixarenes Revisited, Royal Society of Chemistry, Cambridge, U. K., 1998

Gutsche C. D., Calixarenes: an Introduction, RSC Publishing, Cambridge, U. K., 2nd edn, 2008

Mandolini L. and Ungaro R., Calixarenes in Action, Imperial College Press, London, 2000

Mirsky V. M. and Yatsimirsky A., Artificial Receptors for Chemical Sensors, Wiley, Weinheim, 2010

Neri P., Sessler J. L. and Wang M. X., Calixarenes and beyond, Springer, Cham, Switzerland, 2016

Böhmer V. Goldmann H. Vogt W. The first example of a new class of bridged calixarene. J. Chem. Soc., Chem. Commun. 1985:667–668.

Böhmer V. Goldmann H. Kaptein R. Zetta L. Photo-CIDNP studies on calixarenes and bridged calixarenes. J. Chem. Soc., Chem. Commun. 1987:1358–1360.

Böhmer V. Goldmann H. Vogt W. Paulus E. F. Tobiason F. L. Thielman M. J. Bridged calix[4]arenes; x-ray crystal and molecular structures and spectroscopic studies. J. Chem. Soc., Perkin Trans. 2. 1990:1769–1775.

Paulus E. Böhmer V. Goldmann H. Vogt W. The crystal and molecular structure of two calix[4]arenes bridged at opposite para positions. J. Chem. Soc., Perkin Trans. 2. 1987:1609–1615.

Goldmann H. Vogt W. Paulus E. Böhmer V. A series of calix[4]arenes, having two opposite para positions connected by an aliphatic chain. J. Am. Chem. Soc. 1988;110:6811–6817.

Böhmer V. Vogt W. Calix[4]arenes, bridged at the upper rim. Pure Appl. Chem. 1993;65:403–408.

Böhmer V. Goldmann H. Vogt W. Vicens J. Asfari Z. The synthesis of double-calixarenes. Tetrahedron Lett. 1989;30:1391–1394.

Van Loon J. D. Groenen L. C. Wijmenga S. S. Verboom W. Reinhoudt D. N. Upper rim calixcrowns: elucidation of the mechanism of conformational interconversion of calix[4]arenes by quantitative 2-D EXSY NMR spectroscopy. J. Am. Chem. Soc. 1991;113:2378.

Arduini A. Casnati A. Fabbi M. Minari P. Pochini A. Sicuri A. R. Ungaro R. New artificial receptors from selectively functionalized calix[4]arenes. Supramol. Chem. 1993;1:235–246.

Arduini A. Fanni S. Manfredi G. Pochini A. Ungaro R. Sicuri A. R. Ugozzoli F. Direct regioselective formylation of tetraalkoxycalix [4] arenes fixed in the cone conformation and synthesis of new cavitands. J. Org. Chem. 1995;60:1448–1453.

Dondoni A. Marra A. Scherrmann M.-C. Casnati A. Sansone F. Ungaro R. Synthesis and properties of O-glycosyl calix[4]arenes (calixsugars) Chem.–Eur. J. 1997;3:1774–1782.

Banks H. D. Dondoni A. Kleban M. Marra A. Computational and experimental studies of Di- and tetrasubstituted calix[4]arenes. Chirality. 2002;14:173–179. PubMed

Arduini A. McGregor W. M. Pochini A. Secchi A. Ugozzoli F. Ungaro R. New Upper Rim Pyridine-Bridged Calix[4]arenes: Synthesis and Complexation Properties toward Neutral Molecules and Ammonium Ions in Organic Media. J. Org. Chem. 1996;61:6881–6887. PubMed

Arduini A. Cantoni M. Graviani E. Pochini A. Secchi A. Sicuri A. R. Ungaro R. Vincenti M. Gas-phase complexation of neutral molecules by upper rim bridged calix[4]arenes. Tetrahedron. 1995;51:599–606.

Cacciapaglia R. Di Stefano S. Mandolini L. On the 'livingness' of a dynamic library of cyclophane formaldehyde acetals incorporating calix[4]arene subunits. J. Phys. Org. Chem. 2008;21:688–693.

Arimura T. Matsumoto S. Teshima O. Nagasaki T. Shinkai S. Calixarene-based molecular capsule. Tetrahedron Lett. 1991;32:5111–5114.

Düker M. H. Gómez R. Vande Velde C. M. L. Azov V. A. Upper rim tetrathiafulvalene-bridged calix[4]arenes. Tetrahedron Lett. 2011;52:2881–2884.

Düker M. H. Kutter F. Dülcks T. Azov V. A. Calix[4]arenes with 1,2- and 1,3-upper rim tetrathiafulvalene bridges. Supramol. Chem. 2014;26:552–560.

Blanda M. T. Griswold K. E. Synthesis of a Symmetric Octathio Bis(calix[4]arene) Cage Molecule. J. Org. Chem. 1994;59:4313–4315.

Takeda T. Tsubouchi A. Synthesis of alkenes by McMurry coupling and related reductive dimerization reactions. Sci. Synth. 2010;47a:247–325.

Arduini A. Fanni S. Pochini A. Sicuri A. R. Ungaro R. Highly distorted Cone calix[4]arenes through intramolecular mc murry coupling reaction. Tetrahedron. 1995;51:7951–7958.

Lhotak P. Shinkai S. Structurally unusual calix[4]arene derivatives generated by intra- and intermolecular McMurry reactions. Tetrahedron Lett. 1996;37:645.

Haino T. Fukunaga C. Fukazawa Y. A New Calix[5]arene-Based Container: Selective Extraction of Higher Fullerenes. Org. Lett. 2006;8:3545–3548. PubMed

Wang J. Gutsche C. D. Complexation of Fullerenes with Bis-calix[n]arenes Synthesized by Tandem Claisen Rearrangement1. J. Am. Chem. Soc. 1998;120:12226–12231.

Pitarch M. McKee V. Nieuwenhuyzen M. McKervey M. A. Synthesis of bridged, multifunctional calixarenes via ring closing metathesis. J. Org. Chem. 1998;63:946–951.

Struck O. Chrisstoffels L. A. J. Lugtenberg R. J. W. Verboom W. van Hummel G. J. Harkema S. Reinhoudt D. N. Head-to-Head Linked Double Calix[4]arenes: Convenient Synthesis and Complexation Properties. J. Org. Chem. 1997;62:2487–2493. PubMed

Iwamoto H. Niimi K. Haino T. Fukazawa Y. Energetics of guest binding to calix[4]arene molecular containers. Tetrahedron. 2009;65:7259–7267.

Hwang G. T. Kim B. H. Bis-calix[4]arenes with imine linkages: synthesis and binding study of thiopheno bis-calix[4]arene with viologens. Tetrahedron Lett. 2000;41:5917–5921.

Hwang G. T. Kim B. H. Synthesis and binding studies of multiple calix[4]arenes. Tetrahedron. 2002;58:9019–9028.

Arduini A. Ferdani R. Pochini A. Secchi A. Synthesis of Upper Rim Covalently Linked Double Calix[6]arenes. Tetrahedron. 2000;56:8573–8577.

Yilmaz A. Memon S. Yilmaz M. Synthesis and study of allosteric effects on extraction behavior of novel calixarene-based dichromate anion receptors. Tetrahedron. 2002;58:7735–7740.

Chawla H. M. Gupta T. Novel bis-calix [4] arene based molecular probe for ferric iron through colorimetric, ratiometric, and fluorescence enhancement response. Tetrahedron Lett. 2015;56:793–796.

Amr A. E.-G. E. Mohamed A. M. Ibrahim A. A. Synthesis of Some New Chiral Tricyclic and Macrocyclic Pyridine Derivatives as Antimicrobial Agents. Z. Naturforsch., B. 2003;58:861–868.

Sharma S. K. Gutsche C. D. Upper Rim Substitution of Calix[4]arenes via Their Upper Rim A,C Dinitro Compounds1. J. Org. Chem. 1999;64:998–1003. PubMed

Sansone F. Baldini L. Casnati A. Lazzarotto M. Ugozzoli F. Ungaro R. Biomimetic macrocyclic receptors for carboxylate anion recognition based on C-linked peptidocalix[4]arenes. Proc. Natl. Acad. Sci. U. S. A. 2002;99:4842–4847. PubMed PMC

Šťastný V. Lhoták P. Michlová V. Stibor I. Sýkora J. Novel biscalix[4]arene-based anion receptors. Tetrahedron. 2002;58:7207–7211.

Loeb S. J. Cameron B. R. Calixarenes for Separations. Am. Chem. Soc. 2000;757(ch. 21):283–295.

Amr A. E.-G. E.-S. Abo-Ghalia M. Abdalah M. M. Synthesis of Novel Macrocyclic Peptido-calix[4]arenes and Peptidopyridines as Precursors for Potential Molecular Metallacages, Chemosensors and Biologically Active Candidates. Z. Naturforsch., B. 2006;61:1335–1345.

Huisman B.-H. Rudkevich D. M. Farrán A. Verboom W. van Veggel F. C. J. M. Reinhoudt D. N. Synthesis of (Hemi)Carceplex Adsorbates for Self-Assembly on Gold. Eur. J. Org Chem. 2000;2000:269–274.

van Wageningen A. M. Verboom W. Zhu X. Ripmeester J. A. Reinhoudt D. N. Solid state NMR spectroscopy of calix [4] arene-based carceplexes. Supramol. Chem. 1998;9:31–36.

van Wageningen A. M. A. van Duynhoven J. P. M. Verboom W. Reinhoudt D. N. Synthesis and functionalization of calix[4]arene-based carceplexes. J. Chem. Soc., Chem. Commun. 1995:1941–1942.

Timmerman P. Verboom W. van Veggel F. C. J. M. van Duynhoven J. P. M. Reinhoudt D. N. A Novel Type of Stereoisomerism in Calix[4]arene-Based Carceplexes. Angew. Chem., Int. Ed. 1994;33:2345–2348.

van Wageningen A. M. Timmerman P. van Duynhoven J. P. Verboom W. van Veggel F. C. Reinhoudt D. N. Calix [4] arene-Based (Hemi) carcerands and Carceplexes: Synthesis, Functionalization, and Molecular Modeling Study. Chem.–Eur. J. 1997;3:639–654.

Timmerman P. Brinks E. A. Verboom W. Reinhoudt D. N. Synthetic receptors with preorganized cavities that complex prednisolone-21-acetate. J. Chem. Soc., Chem. Commun. 1995:417–418.

Timmerman P. Verboom W. van Veggel F. C. van Hoorn W. P. Reinhoudt D. N. An organic molecule with a rigid cavity of nanosize dimensions. Angew. Chem., Int. Ed. 1994;33:1292–1295.

Tomapatanaget B. Tuntulani T. Lower rim tetra-substituted and upper rim ferrocene amide calix[4]arenes: synthesis, conformation and anion-binding properties. Tetrahedron Lett. 2001;42:8105–8109.

Tomapatanaget B. Tuntulani T. Chailapakul O. Calix[4]arenes Containing Ferrocene Amide as Carboxylate Anion Receptors and Sensors. Org. Lett. 2003;5:1539–1542. PubMed

Iwamoto H. Yukimasa Y. Fukazawa Y. Synthesis and binding behavior of a Zn(II)-porphyrin having calix[5]arene cap. Tetrahedron Lett. 2002;43:8191–8194.

Iwamoto H. Nishi S. Haino T. Highly shape-selective guest encapsulation in the precisely defined cavity of a calix[4]arene-capped metalloporphyrin. Chem. Commun. 2011;47:12670–12672. PubMed

Haino T. Fukuoka H. Iwamoto H. Fukazawa Y. Synthesis and Enantioselective Recognition of a Calix[5]arene-based Chiral Receptor. Supramol. Chem. 2008;20:51–57.

Haino T. Fukuoka H. Katayama M. Fukazawa Y. Enantioselective Recognition of Calix[5]arene-based Artificial Receptor Bearing Chiral Macrocycle for Chiral Ethyltrimethylammonium Salts. Chem. Lett. 2007;36:1054–1055.

Hocquelet C. Jankowski C. K. Mauclaire L. New tubular products from calixarene–cyclodextrin coupling. Tetrahedron. 2007;63:10834–10839.

Kim B. H. Jeong E. J. Hwang G. T. Venkatesan N. Multiple Cycloadditive Macrocyclization: An Efficient Method for Crown Ether-Type Cyclophanes, Bis-Calix[4]arenes and Silamacrocycles. Synthesis. 2001:2191–2202.

Hwang G. T. Kim B. H. Cyclophane-type bis-calix[4]arenes: efficient synthesis via quadruple cycloadditive macrocyclization and conformational study. Tetrahedron Lett. 2000;41:10055–10060.

Zahim S. Wickramasinghe L. A. Evano G. Jabin I. Schrock R. R. Müller P. Calix[6]azacryptand Ligand with a Sterically Protected Tren-Based Coordination Site for Metal Ions. Org. Lett. 2016;18:1570–1573. PubMed

Wickramasinghe L. A. Schrock R. R. Tsay C. Müller P. Molybdenum Complexes that Contain a Calix[6]azacryptand Ligand as Catalysts for Reduction of N2 to Ammonia. Inorg. Chem. 2018;57:15566–15574. PubMed

Phipps D. E. Beer P. D. A [2]catenane containing an upper-rim functionalized calix[4]arene for anion recognition. Tetrahedron Lett. 2009;50:3454–3457.

Miao R. Zheng Q.-Y. Chen C.-F. Huang Z.-T. A novel calix[4]arene fluorescent receptor for selective recognition of acetate anion. Tetrahedron Lett. 2005;46:2155–2158.

Segura M. Bricoli B. Casnati A. Muñoz E. M. Sansone F. Ungaro R. Vicent C. A Prototype Calix[4]arene-Based Receptor for Carbohydrate Recognition Containing Peptide and Phosphate Binding Groups. J. Org. Chem. 2003;68:6296–6303. PubMed

Mai J. H. Liu J. M. Li S. Y. Jiang H. F. A fluorescent probe for fluoride ion based on 2-aminopyridyl-bridged calix[6]arene. Chin. Chem. Lett. 2009;20:1191–1194.

Agrawal Y. K. Sharma K. R. Speciation, liquid–liquid extraction, sequential separation, preconcentration, transport and ICP-AES determination of Cr(III), Mo(VI) and W(VI) with calix-crown hydroxamic acid in high purity grade materials and environmental samples. Talanta. 2005;67:112–120. PubMed

Vysotsky M. O. Bogdan A. Wang L. Böhmer V. Template synthesis of multi-macrocycles by metathesis reaction. Chem. Commun. 2004:1268–1269. PubMed

Molokanova O. Bogdan A. Vysotsky M. O. Bolte M. Ikai T. Okamoto Y. Böhmer V. Calix[4]arene-Based Bis[2]catenanes: Synthesis and Chiral Resolution. Chem.–Eur. J. 2007;13:6157–6170. PubMed

Cao Y. Wang L. Bolte M. Vysotsky M. O. Böhmer V. Synthesis of huge macrocycles using two calix[4]arenes as templates. Chem. Commun. 2005:3132–3134. PubMed

Wang L. Vysotsky M. O. Bogdan A. Bolte M. Böhmer V. Multiple Catenanes Derived from Calix[4]arenes. Science. 2004;304:1312–1314. PubMed

Bogdan A. Vysotsky M. O. Ikai T. Okamoto Y. Böhmer V. Rational Synthesis of Multicyclic Bis[2]catenanes. Chem.–Eur. J. 2004;10:3324–3330. PubMed

Vysotsky M. O. Bolte M. Thondorf I. Böhmer V. New Molecular Topologies by Fourfold Metathesis Reactions within a Hydrogen-Bonded Calix[4]arene Dimer. Chem.–Eur. J. 2003;9:3375–3382. PubMed

Gaeta C. Vysotsky M. O. Bogdan A. Böhmer V. Fourfold [2]Rotaxanes Based on Calix[4]arenes. J. Am. Chem. Soc. 2005;127:13136–13137. PubMed

Molokanova O. Vysotsky M. O. Cao Y. Thondorf I. Böhmer V. Fourfold [2]Rotaxanes of Calix[4]arenes by Ring Closure. Angew. Chem., Int. Ed. 2006;45:8051–8055. PubMed

Bogdan A. Bolte M. Böhmer V. Molecules with New Topologies Derived from Hydrogen-Bonded Dimers of Tetraurea Calix[4]arenes. Chem.–Eur. J. 2008;14:8514–8520. PubMed

Rudzevich Y. Cao Y. Rudzevich V. Böhmer V. Stepwise Synthesis and Selective Dimerisation of Bis- and Trisloop Tetra-urea Calix[4]arenes. Chem.–Eur. J. 2008;14:3346–3354. PubMed

Rudzevich Y. Rudzevich V. Moon C. Brunklaus G. Böhmer V. Self-assembled dendrimers with uniform structure. Org. Biomol. Chem. 2008;6:2270–2275. PubMed

Molokanova O. Podoprygorina G. Bolte M. Böhmer V. Multiple catenanes based on tetraloop derivatives of calix[4]arenes. Tetrahedron. 2009;65:7220–7233.

Chas M. Ballester P. A dissymmetric molecular capsule with polar interior and two mechanically locked hemispheres. Chem. Sci. 2012;3:186–191.

Holub J. Eigner V. Vrzal L. Dvořáková H. Lhoták P. Calix [4] arenes with intramolecularly bridged meta positions prepared via Pd-catalysed double C–H activation. Chem. Commun. 2013;49:2798–2800. PubMed

Stejskal F. Cuřínová P. Lhoták P. Unexpected formation of disulfide-based biscalix[4]arenes. Tetrahedron. 2016;72:760–766.

Zhang X. Tong S. Zhu J. Wang M.-X. Inherently chiral calixarenes by a catalytic enantioselective desymmetrizing cross-dehydrogenative coupling. Chem. Sci. 2023;14:827–832. PubMed PMC

Slavík P. Dudič M. Flídrová K. Sýkora J. Císařová I. Böhm S. Lhoták P. Unprecedented Meta-Substitution of Calixarenes: Direct Way to Inherently Chiral Derivatives. Org. Lett. 2012;14:3628–3631. PubMed

Flídrová K. Böhm S. Dvořáková H. Eigner V. Lhoták P. Dimercuration of Calix[4]arenes: Novel Substitution Pattern in Calixarene Chemistry. Org. Lett. 2014;16:138–141. PubMed

Slavík P. Flídrová K. Dvořáková H. Eigner V. Lhoták P. Meta-arylation of calixarenes using organomercurial chemistry. Org. Biomol. Chem. 2013;11:5528–5534. PubMed

Flídrová K. Slavik P. Eigner V. Dvořáková H. Lhoták P. meta-Bridged calix[4]arenes: a straightforward synthesis via organomercurial chemistry. Chem. Commun. 2013;49:6749–6751. PubMed

Slavík P. Dvořáková H. Eigner V. Lhoták P. Regioselective alkylation of a methylene group via meta-bridging of calix[4]arenes. Chem. Commun. 2014;50:10112–10114. PubMed

Slavík P. Dvořáková H. Krupička M. Lhoták P. Unexpected cleavage of upper rim-bridged calix 4 arenes leading to linear oligophenolic derivatives. Org. Biomol. Chem. 2018;16:838–843. PubMed

Slavík P. Lhoták P. Unusual reactivity of upper-rim bridged calix[4]arenes - Friedel-Crafts alkylation via cleavage of the macrocyclic skeleton. Tetrahedron Lett. 2018;59:1757–1759.

Slavík P. Krupička M. Eigner V. Vrzal L. Dvořáková H. Lhoták P. Rearrangement of meta-Bridged Calix 4 arenes Promoted by Internal Strain. J. Org. Chem. 2019;84:4229–4235. PubMed

Slavík P. Kohout M. Böhm S. Eigner V. Lhoták P. Synthesis of inherently chiral calixarenes via direct mercuration of the partial cone conformation. Chem. Commun. 2016;52:2366–2369. PubMed

Slavík P. Eigner V. Böhm S. Lhoták P. Mercuration of calix[4]arenes immobilized in the 1,2- and 1,3-alternate conformations. Tetrahedron Lett. 2017;58:1846–1850.

Slavík P. Eigner V. Lhoták P. Shaping of calix[4]arenes via double bridging of the upper rim. CrystEngComm. 2016;18:4964–4970.

Slavík P. Eigner V. Lhoták P. Intramolecularly Bridged Calix[4]arenes with Pronounced Complexation Ability toward Neutral Compounds. Org. Lett. 2015;17:2788–2791. PubMed

Slavík P. Dvořáková H. Eigner V. Lhoták P. Meta-Bridged calix[4]arenes prepared by Friedel-Crafts alkylation. New J. Chem. 2017;41:14738–14745.

Slavík P. Eigner V. Lhoták P. meta-Bridged calix[4]arenes with the methylene moiety possessing in/out stereochemistry of substituents. New J. Chem. 2018;42:16646–16652.

Vrzal L. Flídrová K. Tobrman T. Dvořáková H. Lhoták P. Use of residual dipolar couplings in conformational analysis of meta-disubstituted calix[4]arenes. Chem. Commun. 2014;50:7590–7592. PubMed

Tlustý M. Slavík P. Kohout M. Eigner V. Lhoták P. Inherently Chiral Upper-Rim-Bridged Calix[4]arenes Possessing a Seven Membered Ring. Org. Lett. 2017;19:2933–2936. PubMed

Tlustý M. Eigner V. Babor M. Kohout M. Lhoták P. Synthesis of upper rim-double-bridged calix[4]arenes bearing seven membered rings and related compounds. RSC Adv. 2019;9:22017–22030. PubMed PMC

Tlustý M. Spálovská D. Kohout M. Eigner V. Lhoták P. Ketone transformation as a pathway to inherently chiral rigidified calix[4]arenes. Chem. Commun. 2020;56:12773–12776. PubMed

Tlustý M. Eigner V. Lhoták P. Azide Decomposition as a Pathway to Intramolecularly Upper-Rim-Bridged Calix[4]arenes. Synthesis. 2022;54:1301–1308.

Tlustý M. Eigner V. Dvořáková H. Lhoták P. The atropisomeric dynamic behaviour of symmetrical N-acylated amine-bridged calix[4]arenes. New J. Chem. 2022;46:11774–11781.