Cyclophane, helical

Molecules with a single helical unit, such as in hydrogen peroxide, are rare. More commonly found are bundles of two to nine units with coincident central bonds (see Table 1). The combination of two, e.g., in cyclophanes, and four, e.g., in biaryls and allenes, helical units are particularly important. Such compounds have a stereogenic axis, as stereoisomers may be... 

For [2.2]paracyclophane-4-carboxylic acid (25) as (—)(R) This result has been mentioned in a footnote in Ref. 1011 but seems never to have been published (see also Ref. 61). The chirality of this acid was correlated via its ( )-aldehyde with a levo-rotatory hexahelicene derivative which, according to the paracyclophane moiety at the terminal, had to adopt (A/)-helicity. Its chiroptical properties are comparable to those of hexahelicene itself101. For the (—)-bromoderivative of the latter the (A/)-helicity was established by the Bijvoet-method 102). In a later study, (—)para-cyclophane-hexahelicene prepared from (—)-l,4-dimethylhexahelicene with known chirality (which in turn was obtained with approximately 12% enantiomeric purity by asymmetric chromatography) confirmed these results. It should be mentioned that [2.2]paracyclophane-4-carboxylic acid (25) was the first planar chiral cyclophane whose chirality was determined 1041 (see also Ref.54 ). The results justmentioned confirmed the assignment (+)( ). 

Voegtle, F. and Pawlitzki, G. (2002) Cyclophanes from planar chirality and helicity to cyclochirality, in Takemura, H. (ed.), Cyclophane Chemistry for the 21st Century, Research Signpost, Trivandrum, India, pp. 55-90. 

Even the distorted boat-like deck in [2.2]metacyclophanes can be constructed by an intramolecular version of the benzannulation. A suitable precursor bears a chromium vinylcarbene and an allcyne moiety linked to a meta-phenylene core by two-atom bridges, as shown for complexes 80. Benzannulation under the typical conditions affords hydro-quinonophanes 81 in fair yields (Scheme 31) [73]. Interestingly, the intramolecular benzannulation approach even tolerates heteroatom bridges, which impose both additional strain and helicity on the cyclophane skeleton [73b]. 

This approach mimics familiar biological self-assembly phenomena such as protein folding [ 192], protein aggregation [ 192] and nucleotide pairing [ 188]. It incorporates features described in each of the above strategies (i.e., I—III), to give specialized nanoscopic structures, that can be precisely designed, usually with excellent control over CMDPs. Recent examples include so called structure directed synthesis by Stoddart [3a] (see Chapter 1 of this book) to produce toroidal bis-bipyridinium cyclophanes that are reminiscent of a molecular abacus , melamine-cyanuric acid lattices by Whitesides [193] and unique helical structures based on coordination of bipyridyl units to copper (II) ions by Lehn [194],... 

Harren J, Sobanski A, Nieger M, Yamamoto C, Okamoto Y, Vogtle F (1998) A triple layered helical chiral cyclophane - one-pot synthesis, enantiomer separation and chiroptical properties. Tetrahedron Asymmetry 9 1369-1375... 

The application of reaction conditions as optimized in the preparation of the dithia[2.2]phane 88 allowed Meurer and Vogtle [83] to synthesize the first helically chiral dihetera[2.2]metacyclophanes 91 and 92 in 1.9 and 9% yield. It was impossible to isolate these cyclophanes in all the previous attempts where cesium salts had not been applied [84, 85]. 

The corresponding thiopheno-annulated cyclophanes were obtained by Vogtle and co-workers as well [25]. The enantiomers of 15 could be separat their absolute conformation was determined by the method of Bijvoet. The helical pentaphenylenicene 17 was produced similarly [26]. 

Small helical molecules are of interest because of their photophysical and chiroptical properties. Helicenophanes, i.e. helical molecules containing the [2.2]paracyclophane moiety, have been studied due to the peculiar structural properties of the cyclophane framework. Enantiopure compounds have extraordinarily high specific rotation values. Some helical cyclophanes have been prepared " by cycloadditions between [2.2]paracyclophane-based dienes 19 and 20 with dienophiles 1 and 21 (Scheme 7.6). 

Fig. 13A-C. Topological switching of supramolecular structures by oxidation and reduction on metal ions. A The translocation of an Fe2+/3+ ion within a triple helical structure. B The conformation change of a calixarene in response to the oxidation state of an Fe2+/3+ ion. C The translocation of a cyclophane upon the change in oxidation state of a Cu+/2+ ion...

Introduction of the tricarbonylchromium group into cyclophane chemistry has great potential for the preparation of planar- (or helical-)chiral compounds. Besides structure/chiroptics relationships, carrying out stereoselective reactions is of major importance. Recently, inclusion of ferrocenes and benzene-Cr(CO)3 into the cavity of a cyclodextrine was achieved and this makes the connection to supramolecular chemistry [183]. 

The incorporation of arenes in small cyclophanes hinders rotation around certain bonds and can afford isolable enantiomers with appropriately substituted backbones, e.g., planar-chiral 11 (Liittringhaus) or helical-chiral 12 (Vogtle). Studies of the dynamic properties of small cyclophanes with intraannular substituents X (13) provided insight into the space occupancy of atoms or functional groups. ... 

In this chapter, the intermolecular multicomponent aromatic ring construction reactions and intramolecular single-component aromatic ring construction reactions are described. Among them, the [2+2+2] cycloaddition and intramolecular hydroarylation reactions are the most widely employed and reliable method. Various polycyclic and sterically hindered aromatic compounds have been synthesized by this method. In the past 10 years, the asymmetric [2+2+2] cycloaddition and intramolecular hydroarylation reactions have been developed, which enabled the enantioselec-tive synthesis of sterically hindered chiral aromatic compounds, such as axially chiral biaryls, planar chiral cyclophanes, and helically chiral heUcenes. Details of the transition metal-mediated aromatic ring construction reactions are comprehensively covered in the recently published book... 

Often symmetry operations cannot be used in a simple way to classify chiral forms because, e.g., the molecule consists of a number of conformations. Therefore, independent of the symmetry considerations, a chemical approach to describe chiral molecules has been introduced by the use of structural elements such as chiral centers, chiral axis, and chiral planes. Examples for a chiral center are the asymmetric carbon atom, i.e., a carbon atom with four different substituents or the asymmetric nitrogen atom where a free electron pair can be one of the four different substituents. A chiral axis exists with a biphenyl (Figure 3.2) and chiral planes are found with cyclo-phane structures [17]. Chiral elements were introduced originally to classify the absolute configuration of molecules within the R, S nomenclature [16]. In cases where the molecules are chiral as a whole, so-called inherent dissymmetric molecules, special names have often been introduced atropiso-mers, i.e., molecules with hindered rotation about a helical molecules [18], calixarenes, cyclophanes [17], dendrimers [19], and others [20]. 

Figure 6.5. Molecular structure (a) and solid-state structure of helical cyclophane 25 (b).

The same authors also targeted the synthesis of cyclophanes 26-29 that, due to the presence of long alkyl side chains, were expected to possess liquid crystalline properties [13]. Macrocycles 26-29 were isolated in slightly higher yields than 24 and 25, presumably the result of the introduction of the solubilizing side chains. The helical racemic cyclophanes 26-29 were evaluated for liquid crystalline behavior, but these analyses were inconclusive due to the fact that all compounds were a mixture of regioisomers. 

Scheme 6.6. Synthesis of Cso helical cyclophane 39 (R = BU2N). Reagents and conditions ...

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