Chiral cyclophanes

Inspired by the separation ability of cyclic selectors such as cyclodextrins and crown ethers, Malouk s group studied the synthesis of chiral cyclophanes and their intercalation by cation exchange into a lamellar solid acid, a-zirconium phosphate aiming at the preparation of separation media based on solid inorganic-organic conjugates for simple single-plate batch enantioseparations [77-80]. 

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 (+)( ). 

For chemical correlations of planar chiral cyclophanes with centrochiral derivatives for the purpose of applying Horeau s method IOO), see the following section. 

Blomquist Stahl Meinwald Smith J. Org. Chem. 1961,26, 1687. For a review of chiral cyclophanes and related molecules, see SchlOgl Top. Curr. Chem. 1984, 125, 27-62. 

Synthesis, structure and conformational behavior of cyclophanes are of interest. Synthesis of a novel chiral cyclophane consisting of indole as one of the core units was achieved [198]. The first bridge of the cyclophane 273 is formed by a conjugate addition of indole (2) to the unsaturated ketone 269. An intramolecular N-alkylation reaction of 271 resulted in the formation of... 

Recent Theoretical and Experimental Advances in the Electronic Circular Dichroisms of Planar Chiral Cyclophanes... 

Apart from the role of cyclophanes as a model system for studying the electronic interaction between the aromatic moieties, chiral [2.2]paracyclophanes have also been utilized as planar chiral ligands in asymmetric catalysis. Recent advances and applications in this area have been reviewed [5, 6]. The synthesis of heterocyclic compounds based on [2.2]paracyclophane architecture, where the long-distance electronic communication and the planar chirality play significant roles in their application, has also been reported recently [7]. Although the preparation and application of chiral cyclophanes in asymmetric synthesis has attracted much attention for a long time, their chiroptical properties, especially the CD spectra, have rarely been paid attention or even completely ignored. 

The optical resolution of racemic cyclophanes can be easily achieved by chiral HPLC, and the measurement of CD spectra of chiral cyclophanes now becomes a routine. The electronic and magnetic interactions between the aromatic rings can be readily examined if the cyclophane architecture is used in the model systems. Despite this experimental and theoretical progress in relevant fields, the chiroptical properties, especially the electronic CD spectra, of chiral cyclophanes have not been systematically studied until very recently. 

In this section we will congregate the reported CD spectra of chiral cyclophanes. Some recent examples (from the year 2000 onwards) of chiral cyclophanes of particular interest are selected and the reported spectra are visually reproduced. Classical examples are also cited, mostly with their chemical structures, but the figures of CD spectra are omitted. For ease of viewing, one of the enantiomers is drawn in 3D to underline the stereochemistry (i.e., Rp/Sp, M/P, or... 

KanomataN, Ochiai Y (2001) Stereocontrol of molecular jump-rope crystallization-induced asymmetric transformation of planar-chiral cyclophanes. Tetrahedron Lett 42 1045-1048... 

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... 

S R ratio = 5 1) [22]. Yanada and Yoneda constructed the deazaflavinophane 26, which exhibits complete facial selectivity in its oxidation and reduction reactions, e.g. the reduction with NaBD to afford 27 [23], Belokon and Rozen-berg used scalemic 4-formyl-5-hydroxy[2.2]para-cyclophane (FHPC) 28 in the synthesis of a-ami-no acids (ee 45-98 %) [24], An alternative approach to FHPC was more recently reported by Hopf [25]. Other interesting advances in the area of chiral cyclophanes include the homochir-al [2.2]paracyclophane-derived amino acids 29 and 30 [26], as well as (5)-PHANEPHOS (31) [27], which has been shown to be an effective ligand for highly enantioselective Ru-catalyzed asymmetric hydrogenations of -ketoesters and... 

Figure 8. A polyamine dendrimer bearing planar-chiral cyclophane units (Vogtle et al.)...

Garcia, M.E. Gavin. J.A. Deng. N. Andrievsky, A.A. Mallouk, T.E. Combinatorial synthesis of modular chiral cyclophanes. Tetrahedron Lett. 1996, 37. 8313-8316. 

Although the chirality of cyclophanes was recognized more than 50 years ago by Liittringhaus and Gralheer in ansa compounds [14], chiral cyclophanes have been applied as auxiliaries and ligands in asymmetric synthesis only recently. Some examples of this exciting use of cyclophanes will be given. 

Chiral Cyclophanes as Auxiliaries and Ligands for Asymmetric Catalysis... 

Hochmuth, D.H. Koenig, W.A. Determination of the rotational energy barrier of planar-chiral cyclophanes using dynamic enantioselective gas chromatography and computer simulation. Liebigs Ann. 1996, 6, 947-951. 

Although not very efficient at present, these results clearly show that chiral cyclophanes provide chiral cavities which can recognize and induce chirality in the bound guests. 

In 2002, Shair and coworkers [44] utilized ethylene as an additive in the macrocyclic ene-yne metathesis to form the planar chiral cyclophane 80 [43]... 

SCHEME 21.22 Enantioselective synthesis of planar chiral cyclophanes. 

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... 

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