Optically active guests

Since the optically active host remaining after separation of the optically active guest from its inclusion complex by distillation can be used again and again, this one-pot method in water is an ecological and economical method [12]. 

Systems exhibiting chiral recognition. Complexation of an optically active guest molecule (+)G or (-)G by a chiral host (—)H may be represented as follows ... 

As the cyclodextrins are chiral molecules, a racemic mixture of an optically active guest species has the possibility of forming two diaste-reomers on complexation with cyclodextrin, that is,... 

Such twisted nematic phases are called induced cholesteric solutions and - as schematically outlined in Fig. 4.6-9 - enantiomers cause countercurrently twisted structures. As discussed by Korte and Schrader (1981) this effect offers the potential of sensitively characterizing the chirality of small amounts of optically active compounds. There are no restrictions as to the type of chirality, and the experiments can advantageously be based on infrared spectroscopy. The application of induced cholesteric solutions was later reviewed again by Solladie and Zimmermann (1984). The host phase is the more twisted the more of the optically active guest compound is dissolved. Quantifying the twist by the inverse pitch z and the concentration by the molar fraction x, the ability of a chiral. solute to twist a given nematic host phase is characterized by the helical twisting power (HTP Baessler and Labes, 1970). For small values of a this quantity P is defined by the relation... 

We highlight here a few studies in which the synthesis of chiral molecules has been achieved through the use of organic crystals in the hopes that this will prove a useful incentive and review. The reported studies fall into two natural categories. In the one case one starts with racemic mixtures or optically inactive compounds, crystallize these materials into chiral crystals and finally by subsequent reactions, trap this chirality in the final chemical products. In the second category one forms host-guest inclusion compounds in which the host is already an optically resolved compound. This in turn leads to the formation of optically active guest molecules. 

The enantiomers of the host compound 92 could be separated starting with the racemate using an optically active guest (sparteine), too. 

If host and guest molecules mutually recognize their chiralities at inclusion formation, the process could be used for optical resolution. In other words, when the host compound is optically active, one enantiomer of the guest compound should be included selectively. In turn, if an optical active guest molecule forms a crystal inclusion with one enantiomer of the host compound selectively, the host compound yields resolved. This section deals with the resolution via inclusion formation using host compounds such as alkaloids, 2-propyn-l-ols, 2,4-hexadiyne-l,6-diols, 2,2 -dihydroxy-l,r-binaphthol (7), and 2,2 -dihydroxy-9,9 -spirobifluorene (10a). 

Optically active thiiranes have been obtained by resolution of racemic mixtures by chiral tri-o-thymotide. The dextrorotatory thymotide prefers the (5,5)-enantiomer of 2,3-dimethylthiirane which forms a 2 1 host guest complex. A 30% enantiomeric excess of (5,5)-(—)-2,3-dimethylthiirane is obtained (80JA1157). 

The question that emerges at the climax of this survey relates to the possibility of using crystalline inclusion phenomena for optical resolutions of molecular species. Can this be done effectively with suitably designed host compounds The definitely positive answer to this question has elegantly been demonstrated by Toda 20) as well as by other investigators (see Ch. 2 of Vol. 140). An optically active host compound will always form a chiral lattice. Therefore, when an inclusion type structure is induced, one enantiomer of the guest moiety should be included selectively within the asymmetric environment. 

The possibility to resolve the two enantiomers of 27a (or 26) by crystalline complexa-tion with optically active 26 (or 27a) is mainly due to differences in topological complementarity between the H-bonded chains of host and guest molecules. In this respect, the spatial relationships which affect optical resolution in the above described coordination-assisted clathrates are similar to those characterizing some optically resolved molecular complexes S4). This should encourage additional applications of the lattice inclusion phenomena to problems of chiral recognition. 

When guest molecules are arranged together in the channel of a host-guest inclusion complex, intermolecular reactions of the guest compound may proceed stereoselec-tively and efficiently. An enantioselective reaction is expected when optically active host compounds are used. 

An enantioselective photoreaction of a guest compound is expected when an inclusion complex of the guest with an optically active host compound is irradiated in the solid state. 

The polymerization of trans-1,3-pentadiene, 149, in a chiral channel inclusion complex with enantiomerically pure perhydrotriphenylene affords an optically active polymer, 150 (236). Asymmetric polymerization of this monomer guest occurs also in deoxycholic acid inclusion complexes (237). 

Irradiation in air of the deoxycholic acid (DCA, 157) complex of indanone leads to oxidation of both the steroid and the guest, yielding 5- 3-hydroxy-DCA, 158, and optically active 3-hydroxyindanone (241). In the presence of air, irradiation of the DCA clathrates of isochromane, 159, and indene, 161, leads to reaction with oxidation of the host and of the allylic position of the guest to a keto group (e.g., 159 — 160 and 161 — 162).The detailed mechanisms of these oxidations remain to be elucidated. 

Chiral recognition. The use of chiral hosts to form diastereomeric inclusion compounds was mentioned above. But in some cases it is possible for a host to form an inclusion compound with one enantiomer of a racemic guest, but not the other. This is called chiral recognition. One enantiomer fits into the chiral host cavity, the other does not. More often, both diastereomers are formed, but one forms more rapidly than the other, so that if the guest is removed it is already partially resolved (this is a form of kinetic resolution, see category 6). An example is use of the chiral crown ether 42 partially to resolve the racemic amine salt 43.121 When an aqueous solution of 43 was mixed with a solution of optically active 42 in chloroform, and the layers separated, the chloroform layer contained about... 

Figures 53 and 54 show the structure of the 3/98d complex as it exists in the unit cell [154, 303], Unlike the complexes with 98a-c, the 98d complex has both hydroxyl groups of one 3 hydrogen bonded to both carbonyl groups of one molecule of 98d. As a result, the diyne backbone is curved (Figure 53) [154, 303], There is no reason to believe that the walls of the reaction cavity experienced by 98d or by transients, lOld and 102d derived from it, in optically active 3 complexes are any more rigid or contain less free volume than do the other complexes. The enantiomeric purity of the product must result from specific attractive host-guest interactions retained along the...

It has also been reported from circular dichroism (CD) studies [36] that polysaccharide-based CSPs can induce chirality in enantiomeric guests such as (4Z,15Z)-bilirubin-Ixoc (BR) (Fig. 5). Although not optically active, BR has two enantiomeric helical conformations maintained by six intramolecular hydrogen bonds between two carboxylic acid moieties and two pyrromethenone — NH— protons. These (R)- and (5)-helical conformers are in dynamic equilibrium in an achiral solution [37], but some optically active compounds can enantioselectively bind to BR to induce CD spectra in solution [38-40]. A significant induced CD... 

Some of the first, and most versatile hosts are compounds 3a-c, which can be prepared from optically active tartaric acid. It has been found that they work as chiral selectors in solution [17], and in a powdered state [18], In the crystal structure of the free host compound (R,R)-(—)-fra s-bis(hydroxydiphenylmethyl)-l, 4-dioxaspiro[4.5]decane (3c), only one hydroxyl group is intramolecularly hydrogen bonded (Figure 1). As long as no suitable guest molecules are present, the other OH-group remains unbonded in both media. 

Among the different types of compounds whose complexation properties have been studied are various amides linear oxoamide 9 [22], fumaramide 10 [23,24] and methanetricarboxamide 11 [25], biphenyl derivatives 12 [26], and derivatives of tartaric acid 13-16, that can also be prepared in an optically active form [27], The above-mentioned chiral hosts have been found to form inclusion complexes with chiral guests 17 and 18. Molecular recognition between chiral hosts and... 

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