Chiral calixarenes calix arenes

Calixarene esters are easily available by alkylation with ethyl bromoacetate and are often used as starting materials for the introduction of chiral groups at the narrow rim. Their aminolysis by chiral amines led to chiral calixarene derivatives in high yields. Water soluble calix[4]arene amino acid derivatives 9a,b obtained in this way, were successfully used as a pseudostationary phase... 

The most obvious way to generate a chiral calixarene is by attachment of a chiral moiety. This was achieved as far back as 1979 by esterification with camphorsul-fonyl chloride,a chiral moiety which has again more recently been incorporated into a calix[4]arene. Several other examples have also been published describing the attachment of the chiral moiety at the lower rim via ether linkage. 

A more subtle way to generate a chiral calixarene is to create dissymmetry or asymmetry within the molecule itself One of the means for doing this with a calix[4]arene is to establish a substitution pattern of AABC or ABCD on the upper or lower rim, producing a compound that is inherently chiral in all possible conformations. Tabulations of the cone, partial cone, 1,2-alternate, and... 

Attachment of chiral substituents to calixarene skeleton is the first, the most straightforward and still the most popular way to constmct chiral calixarenes. In 1979 Gutsche reported the synthesis of the first chiral calixarene by attaching camphorosulfonyl group to p-tBu-calix[8]arene [1]. Nowadays, attachment of virtually any chiral moiety at the selected position is synthetically feasible. However, some chiral groups, due to their availability and versatility, have been particularly widely exploited, for example amino acid derivatives, peptides, carbohydrates, chiral amines and axially chiral groups. 

In contrast, the H-NMR spectrum of 4 shows resonances for the tert-butyl protons at <5 1.28, for the methylene protons at 6 3.59, 5.13 (Jab = 15.1 Hz), and for the aromatic protons at S 7.02, 7.21, indicating a symmetrical structure. These signals correspond to symmetric structures, RRRR/SSSS or RSRS, described above. Recently, chiral calixarenes have been reported by many groups [22]. Bbhmer and coworkers [23] demonstrated the chirality of dissymmetric calix[4]arenes with... 

A homodimer of a tetra-urea calix[4]arene consisting of identical phenolic units A is composed of two enantiomers with C4-symmetry, which results in overall S8-symmetry. Consequently, a heterodimer with a second calixarene consisting of four units B must be chiral, but this chirality is due only to the directionality of the hydrogen-bonded belt or (in other words) to the orientation of the carbonyl groups [42,43]. Rotation around the (four) aryl-NH bonds leads to the opposite enantiomer (conformational chirality). 

Chiral recognition by calixarenes in the gas phase is virtually unknown.458-460 To date, only few very recent gas-phase studies on this subject can be retrieved from the literature, i.e., (i) a gas-phase study on the displacement of several amino acids from the chiral amido4resorcinarene 9 (Scheme 9) carried out by Speranza and coworkers using an electrospray-ionization Fourier-transform ion cyclotron resonance (ESI-FT-ICR) mass spectrometer,461 462 and (ii) Lebrilla and coworkers study on the ability of the achiral calix[4]arene 7 and calix[6]arene 8 to form inclusion complexes with natural amino acids under matrix-assisted laser desorption ionization (MALDI) conditions.459... 

Recent examples of calixarenes having chiral substituents attached to the wide rim are calix[n]arenes la and lb which were obtained by one-pot synthesis from the respective p-substituted phenol in moderate15 to low yield.16... 

Chiral calix[4]arene podands were made using A-benzyl histidine methyl ester.33 These histidyl calixarenes 12a,b were studied in complexation experiments with Co(H), but no use was made of their chirality. The same is true for a chiral calix[4]arene capped tetraphenyl porphyrin which is C4-symmetrical due to the four L-alanine derived linkers.34... 

It should be mentioned, that larger assemblies consisting of nine calixarenes are available with the calixarene-monocyanurate 139,208a while the double-calixarene 140 forms a double-box with 136 consisting of 15 molecules (3 x 140 and 9 x 136).283 Polymeric aggregates are formed between bis-melamine and bis-cyanurate calix[4]arenes.284 In all these cases, chiral induction still remains to be explored. 

Three equivalents of a calix[4]arene derivative, diametrically substituted at its upper rim with two melamine units, have also been demonstrated to yield well-defined box-like assemblies on interaction with six equivalents of 5,5-diethylbar-bituric acid. The product, which is based on an extended rosette motif, consists of nine different components held together by 36 hydrogen bonds. It is stable in apolar solvents and remains so even at very low concentrations. Further, the structure remains intact in the solid state, as confirmed by an X-ray diffraction study. In an extension of this study, three enantio-pure calix[4]arene-dimelamine derivatives were employed for a parallel study. In this instance, the chiral information in the individual calixarene derivatives proved successful in controlling the conformation of the final assembly - a homochiral supramolecular entity was the result. 

Interest in phosphorus-containing calixarenes continues. Structures reported include hexa(diethoxyphosphoryloxy)calix[6]arene (8), inherently chiral 1,2-bridged calix[4]arene diphosphates, and a calixarene like C3 symmetric receptor with a phosphate function at the cavity bottom. " The purification of phosphate substituted calixarenes has been studied by chiral HPLC and by normal reverse phase HPLC. Mono(6-0-diphenoxyphosphoryl)-P-cyclodextrin (9) and mono(6-0-ethoxyhydroxyphosphoryl)-p-cyclodextrin (10) have been synthesised and show enantioselective inclusion of D and L amino acids e.g. 3.6 for D/L serine in the case of 9). ... 

Chirality in calixarenes and resorcinarenes can be essentially of two different types, depending on the method used for generating it. The first type, called chirality by attachment, consists of the introduction of a chiral, nonracemic, moiety onto the calixarene or resorcinarene framework. The second type, often referred to as inherent chirality, has been particularly studied for calix[4]arenes, and it is usually observed when three (AABC) or four different phenolic units are present in the macrocycles (Figure 24). As this type of chirality is linked to the nonplanar shape of calix[4]arenes, the well-known ring inversion of these compounds must be avoided through functionalization at the lower rim to obtain stable enantiomers. 

The unique feature of calixarenes is their concave structure that clearly distinguishes the upper and lower rims. When the inversion of the concave structure is hindered, an asymmetric/dissymmetric substitution pattern leads to the formation of chiral structures (Fig. 2.14). This type of chirality is known as inherent chirality. Calix[4]arenes were the first scaffolds for which the term inherent chirality was... 

Limitations on the application of hydrogen bonded capsular assemblies come from the poor stability of these assemblies in polar media compared to those held by covalent bonds. In an attempt to overcome these Umitations, Bohmer described the synthesis of a mechanically locked chiral bis-catenane based on calixarene capsules [55]. Inspired by this pioneering work, our group produced a mechanically locked hybrid tetraurea calix[4]arene-calix[4]pyrrole capsule 30 (Fig. 32.14) [56]. This catenated capsule displayed reversible encapsulation (i.e. reversible assembly of the urea belt). The two hemispheres of the capsule never dissociate completely due to the bis-catenated topology. 

Inherently chiral derivatives are also known from calix[8]arenes. Dimetalla complexes were obtained with titanium (as well as with Zr, V, Sn) in which the two titanium atoms have a pseudooctahedral environment bonded to all of the eight calixarene oxygens, two of which are bridging, and two isopropoxide oxygens. The C2 symmetry was proved by single crystal X-ray analysis and in solution by two-dimensional H-NMR spectroscopy [28]. Various complexes of r-butylcalix[8]arene with lanthanide ions have a similar structure [29]. 

Although chiral calix[4]arenes can be generated by simply attaching chiral residues at the upper [40] or lower [41-43] rim of the calixarene skeleton, recent interest has been focused on the possibility of synthesizing inherently chiral calix[4]arenes, which are build up of nonchiral subunits and consequently owe their chirality to the fact that the calixarene molecule is nonplanar. Molecular asymmetry can arise from the substitution pattern at the lower rim and/or conformation. In this respect, Shinkai has recently reported a systematic classification of all possible chiral isomers derivable from calix[4]arene, and delineated some basic concepts for the design and synthesis of chiral derivatives [44]. 

Calix[4]resorcinarenes 76 are tetrameric cavity compounds produced by the reaction of an aldehyde and resorcinol (Figure 50.24). Calixarenes 77 are produced by the reaction of phenol and formaldehyde. Chirality in calixarenes and calix[4]resorcinarenes is usually achieved by the addition of enantiomeric ally pure moieties. Although several calLx-arenes and calix[4]resorcinarenes have been examined as chiral NMR shift reagents, only one particular family of water-soluble calix[4]resorcinarenes 78-82 has been widely studied. " ... 

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