Chiral helicenes

Toda, F. and Tanaka, K., (1994) A new simple chiral helicene 3,4-bis(diphenylmethylene)-iV-methylsuccinimide in its chiral crystal. A generation of chirality, Supramol. Chem., 3, 87-88. 

Finally, some rather exotic ferrocenes must be mentioned that are formed from chiral helicenes having five-membered terminal rings by deprotonation and reaction with FeCl2-THF complex (Fig. 4-13, bottom) [87, 88]. Such materials have unusual optical properties, e g., extremely high optical rotations. 

Several polyarenes obtained by palladium-catalyzed cocycloaddition of arynes and DMAD are conformationally stable chiral helicenes. For example, cocycloaddition of aryne 141 and DMAD affords a mixture of polyarenes from which helicene 142 can be isolated in yields up to 30%. Furthermore, this reaction proceeds with good enantioselectivity when performed in the presence of chiral bidentate ligands such as BINAP, which leads to an ee of 67% when the solvent is THF (Table 5, entry 2) [73]. 

Interesting nonlinear optical properties were shown by chiral helicenes (5) forming LB films with larger second-order susceptibility than corresponding racemic structures. Nanotubes based on cyclic peptides were reported to form membranes with ion-selective channels. 

As mentioned previously, the helicene-based chlorophosphite M,M,R) 25a, which is easily prepared from the reaction ofenantiopure (M,M,R)-[5 -HELOL 24a with phosphorus trichloride, has been successfirUy used to analyze the enantiomeric compositions of a variety of chiral materials such as alcohols, amines, or carboxylic acids. The reaction is conducted in an NMR tube where the analytes are added to the chiral helicene-based chlorophosphite in CDCI3. After 2 h reaction, the diastereomers ratios generated in situ are determined by P-NMR spectroscopy. Notably, this attractive method has proved to be highly efficient for analyzing the enantiomeric purities of a wide range of molecules whose stereogenic centers are far away from functional groups that react with phosphorus atom. The authors... 

Before synthetic chiral stationary phases were developed, attempts were made to use naturally occurring chiral materials for the stationary phase. Quartz, wool, lactose and starch were inadequate but triacetylated cellulose has met with some success. The synthetic stationary phases introduced by Pirkle are able to interact with solute enantiomers in three ways, one of which is stereochemically dependent. Typically these interactions are based on hydrogen bonding, charge transfer (rc-donoi -acceptor based) and steric repulsive types. An independent chiral stationary phase therefore consists of chiral molecules each with three sites of interaction bound to a silica (or other) support. Early work in this area demonstrated that 5-arginine bound to Sephadex would resolve 3,4-dihydroxy-phenylalanine, and that direct resolution of chiral helicenes could be accomplished with columns packed with 2-(2,4,5,7-tetranitro-9-fluorenylideneaminoxy)-propionamide or tri-P-naphthol-diphosphate amide. Amino acid esters have also been resolved with a silica bound chiral binaphthyl crown ether, but better separations are achieved with A-acylated amino acid derivatives with amino-acid derived chiral stationary phases. 

A new approach to second-order nonlinear materials was reported by Verbiest et al. (56) in which chirality plays the key role. These authors investigated Langmuir-Blodgett films of chiral helicenes which lack features commonly associated with a high SHG response. The molecules adopt a helical structure on a solid support and this chiral supramolecular arrangement enhances the second-order NLO susceptibility by a factor of 30 when compared to the corresponding racemic mixture. An adequate description of the SHG response in a chiral system requires additional tensor elements. Experimental evidence was provided that those tensor elements which are only allowed in a chiral environment dominate the SHG response of the helicene system. 

Chiral helicenes (288) having Iff-phosphindoles as structural unit were S3mthesized via diastereoselective intramolecular photocyclization. These helicenes gave [2 + 2] photocylodimers (290). Intramolecular [2 + 2] photocycloaddition of chiral [7]saddlequat (290) afforded [8]circulenoid (291) (Scheme 61). ... 

If compounds have the same topology (constitution) but different topography (geometry), they are called stereoisomers. The configuration expresses the different positions of atoms around stereocenters, stereoaxes, and stereoplanes in 3D space, e.g., chiral structures (enantiomers, diastereomers, atropisomers, helicenes, etc.), or cisftrans (Z/E) configuration. If it is possible to interconvert stereoisomers by a rotation around a C-C single bond, they are called conformers. 

Armstrong and Jin [15] reported the separation of several hydrophobic isomers (including (l-ferrocenylethyl)thiophenol, 1 -benzylnornicotine, mephenytoin and disopyramide) by cyclodextrins as chiral selectors. A wide variety of crown ethers have been synthesized for application in enantioselective liquid membrane separation, such as binaphthyl-, biphenanthryl-, helicene-, tetrahydrofuran and cyclohex-anediol-based crown ethers [16-20]. Brice and Pirkle [7] give a comprehensive overview of the characteristics and performance of the various crown ethers used as chiral selectors in liquid membrane separation. 

Many molecules are chiral - that is, these molecules are not superimposable on their mirror images. One way for molecules to obtain chirality is to have so-called asymmetric carbons (that is, a carbon atom with four covalent bonds, none of which are equivalent). But there are many other structures that are also chiral, ranging from helicenes through simple twisted molecules such as biphenyl. 

Nuckolls and Katz have synthesized discotic liquid crystalline molecules in which the core is a helix in its own right.37 Nonracemic helicene 33 was found to assemble into a columnar mesophase in which the helicenes stack on top of each other. CD spectroscopy showed a strong increase of the Cotton effect upon going from the molecularly dissolved state to the aggregated state, exhibiting an amplification of chirality. These helical columns give rise to a strong expression of chirality because the intrinsic shape of the helicenes... 

Metal phthalocyanines functionalized with four helicenes (62) have also been reported to form chiral columnar aggregates.76 In chloroform solutions of these metal phthalocyanines aggregation into columns occurred upon addition of ethanol, as was observed by UV-Vis spectroscopy. CD spectroscopy revealed that the chromophores within the columnar aggregates are in a chiral environment, implying that the chirality of the peripheral helicenes has been transferred to the supramolecular aggregates. These phthalocyanines stack with a typical intermolecular distance of 3.4 A, and calculations have indicated that to allow this distance the two phthalocyanine moieties have to be rotated because of the bulkiness of the helicenes. It can easily be imagined that a phthalocyanine provided with both R and S helicenes cannot stack in such a defined manner because of the steric interactions between the nonconform helicenes. 

A last example of a dopant whose chirality has been investigated by the LC technique is represented by helicenes and related molecules. Once again, compounds very different spectroscopically, such as 46-49, and hence hardly comparable with chiroptical techniques, are very similar in shape and give helical twisting powers of the same sign and of comparable intensity80 the twisting powers of helicenes have been successfully calculated by the shape model of Ferrarini et al.73... 

The systems discussed up to now all showed chiral susceptibilities that were of the same order of magnitude or smaller than the achiral susceptibility components. The system that we discuss in this section has chiral susceptibilities that dominate the nonlinear optical response.53 The material is a chiral helicenebisquinone derivative shown in Figure 9.22. In bulk samples, the nonracemic, but not the racemic, form of the material spontaneously organizes into long fibers clearly visible under an optical microscope. These fibers comprise columnar stacks of helicene molecules.54,55 Similar columnar stacks self-assemble in appropriate solvents, such as n-dodecane, when the concentration exceeds 1 mM. This association can be observed by a large increase in the circular dichroism (CD) of the solutions. 

That chiral molecules can be produced in a CPL field, either from achiral precursors by photo-activated synthesis or by preferential chiral photodestruction of a racemic mixture, is now well demonstrated and has been reviewed. [46] In all cases currently known, however, such processes have proved very inefficient. For example, asymmetric photochemical ring-closures of achiral helicene precursors induced by CPL have produced only about 0.2% e.e. in the products. Likewise, the CPL-induced photolysis of racemic camphor produced about 20 % e.e., but only after 99% photodestruction, and photolysis of D.L-glutamic acid produced only 0.22 % e.e. after 52 % photodecomposition. [71]... 

Another mechanism of chiral amplification that extends over an even larger scale has been reported by Huck et al. [119] The molecule 12-(9 H-thioxantbene-9 -yli-dene-12H-benzo[a]xanthene (Fig. 11.6), which has no chiral center, nevertheless exists, like the helicenes, in two chiral forms defined by their enantiomeric configurations. Consistent with the discussion in Section 11.2.3, a small net handedness (ca. 0.7 %) could be induced in racemic solutions of this molecule by use of ultraviolet CPL. However, introducing 20 wt% of this molecule, which contained a 1.5% chiral excess of one roto-enantiomer, into a nematic phase of liquid crystals produced macroscopic (100 pm) regions of a chiral cholesteric liquid crystal phase. The... 

Laarhoven et al. 711 have studied the influence of chiral solvents on the optical yield of [6]helicene, synthesized by photodehydi ocyclization of various precursors. Most thoroughly investigated was the photochemical ring closure of 2-styrylbenzo[c]-phenanthrene in optically active fluids (Table 5). 

Macroscopical helical structures formed by cholesteric liquid crystals have been used as chiral helical media for the asymmetric synthesis of helicenes. 

The stereoselective formation of helicene skeletons by photocyclodehydrogenation of 1,2-diarylethylenes carrying a chiral group had been studied systematically by Martin et al. 

In order to study the influence of a given chiral group at different positions in the precursor styrylbenzo[c]phenanthrene several carboxy styrylbenzo[c]phenanthrenes were synthesized and esterified with chiral alcohols, and the products were used to prepare hexahelicenes 76 substituted at various positions. The bromo-esters (29) were used as precursors for [6]-helicenes, substituted at position 1. 

Chiral group Rin 75 Position in helicene 76 Ratio of diastereomeric helicenes Ref. 

M)-[ll]-, and (M)-[13]-helicene 31). Wittig reactions between (M)-(—)-formyl-hexahelicene and suitable phosphonium salts led to 1,2-disubstituted ethylenes, all containing the same chiral moiety, which could be subjected to photocyclodehydrogenation (Table 1). 

The first resolution of [6]-helicene was achieved by Newman and Lednicer 78) by crystallization with the aid of a chiral complexing agent, 2-(2,4,5,7-tetranitro-9-fluorenylidene aminooxy)propionic acid (TAPA), which was especially designed for this purpose. (R)- and (S)-TAPA (79 a) form diastereomeric charge-transfer (CT) complexes with the enantiomers of hexahelicene. Several other helicenes could also be resolved using this reagent. 

Resolution of helicenes has also been performed by the very laborious method of picking single crystals 4,5 29,79,80). After recrystallization of the partially resolved mixture the procedure can be repeated, until no more variation in optical rotation occurs. Because some helicenes crystallize into racemic crystals by lamellar intergrowth of pure P and pure M forms (see Sect. 6) the crystal picking method is not always applicable, however. A [7]-heterohelicene was partially resolved by crystallization from the chiral solvent54) (—>x-pinene. 

Wijnberg 86) separated several heterohelicenes on aluminium oxide coated with TAPA. The resolution factors are comparable with those of TAPA on silicagel they ranged from r = 1.12 for [7J-BOBBBOB to 1.20 for hexahelicene and some thiahexahelicenes. Other chiral selectors have been tested as to their usefulness for the resolution of helicenes. Binaphthyl-2,2 -diylhydrogenphosphate (BPA) (80) raised great expectations 88) because its chirality is of the same kind as that of... 

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