Inclusion enantioselective

Some solid-solid reactions were shown to proceed efficiently in a water suspension medium in Sect. 2.1. When this reaction, which gives a racemic product, is combined with an enantioselective inclusion complexation with a chiral host in a water suspension medium, a unique one-pot preparative method of optically active product in a water medium can be constructed. Some such successful examples are described. 

The enantioselective inclusion complexation of the reaction product with lOa-c in aqueous medium is more efficient than that by the recrystallization method. For example, inclusion complexation of rac-65e with 10a,b did not occur by recrystallization from an organic solvent however, enantioselective complexation occurred efficiently in aqueous medium to give finally optically active 65e [12]. 

As discussed in detail in Ref. 36, for use in optoelectronics only systems crystallizing in non-centrosymmetric crystal lattices are of interest if the use of expensive enantiomers of chiral molecules is to be avoided. This considerably limits the available crystal lattices since most organic achiral molecules crystallize into centrosymmetric space groups. An interesting example of enantioselective inclusion complexation was reported by Gdaniec and coworkers [37]. 

Another variation of the enantioselective inclusion complexation procedure leading to optical resolution is the application of powdered host compounds in the... 

When a solution of rac-4-methyl-l-(hydroxyimino)cyclohexane (20) and 1 in diethyl ether-petroleum ether was kept at room temperature, a 1 1 inclusion compound of (-)-20 of 79% ee and 1 was obtained as colorless needles by an enantioselective inclusion complexation. Heating of the inclusion compound... 

Preparation of optically active P-ionone epoxide by a solid state kinetic resolution in the presence of the chiral host 10a is also possible. When a mixture of 10a, P-ionone (66) and m-chloroperbenzoic acid (MCPBA) is ground by mortar and pestle in the solid state, (+)-67 of 88% ee was obtained.29 Mechanism of the kinetic resolution is shown below. Of course, all processes proceed in the solid state. Firstly, oxidation of 66 with MCPBA gives rac-P-ionone epoxide (67). Secondly, enantioselective inclusion of (+)-67 with 10a occurs. Thirdly, uncomplexed (-)-67 is oxidized to give the Baeyer- Villiger oxidation product (-)-68 of 72% ee. This is the first example of the resolution by an enantioselective inclusion complexation in the solid state. 

Zaderenko, P, Lopez, P, Ballesteros, P., Takumi, H., and Toda, F. (1995) Resolution of 2-Azol-l-ylsucccinic Esters by Enantioselective Inclusion Methodology, Tetrahedron Asymm.,... 

Akazome, M., Ueno, Y., Ooiso, H., and Ogura, K. (2000) Enantioselective Inclusion of Methyl Phenyl Sulfoxides and Benzyl Methyl Sulfoxides by (i )-Phenylglycyl-(i )-phenylglycine and the Crystal Structures of the Inclusion Cavities, J. Org. Chem. 65, 68-76. 

Although enantioselective inclusion into the chiral clefts formed by the polymer network may play a minor role in the chiral recognition mechanism, enantiodiscrimina-tion is primarily driven by hydrogen bonding and/or Ti-TT-interactions. A representative selection of successfully resolved racemates employing synthetic polymeric CSPs is listed in Table 9.7. 

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). ... 

Recently an improvement in this separation technique was reported, which seemed to indicate that enantioselective inclusion in the lattices of chiral hosts could be employed on a large scale. [11] When crystalline hosts such as R,R)-(-)-S (m.p. 196 °C), [12] (/ ,/ )-(-)-9 (m.p. 165 °C), [12] and (5,5)-(-)-10 (m.p. 128 °C) are suspended in hexane or water, chiral guest molecules form the same inclusion compounds as from solution. This is by no means self-evident, since inclusion compounds have different crystal lattices than the pure host crystals. Thus crystal/liquid reactions occur, and phase rebuildings analogous to those observed in gas/solid reactions [13] must take place. Yet this suspension technique is more selective and more effective than the initially developed solution technique. Numerous racemic alcohols like 11, -hydroxy esters like 12, epoxy esters like 13, and epoxy ketones like 14 were stirred a few hours with appropriate hosts (suspensions of 8, 9, and 10) and formed 1 1 complexes that could be filtered off in yields of > 85 % and with ee values of > 97 % (the complex of 12 and 9 formed in hexane only 80% ee in one step). Recrystallization of the inclusion... 

Host-guest inclusion complexations are usually carried out in organic solvents. As a green process, inclusion complexation can be performed in a water suspension medium or in the solid state. When the solid-state reaction in a water suspension medium is combined with an enantioselective inclusion complexation in the same water medium, a one-pot green preparative method for obtaining optically active compounds can be designed. In all these cases, enantiomers separated as inclusion complexes are recovered by distillation of the inclusion complex. When enantioselective inclusion complexation in the solid state is combined with the distillation technique, a unique green process for enantiomeric separation can result. 

In this section, one-pot preparations of optically active compounds by a combination of solid-state reaction and enantioselective inclusion complexation in a water suspension medium are described. In order to establish the suspension procedure as a general enantiomeric separation method, enantiomeric separations of various compounds by complexation in hexane and water suspension media were studied. Furthermore, by combining enantioselective inclusion complexation with a chiral host in the solid state with distillation, a fascinating enantiomeric separation method by fractional distillation was established. 

Cellulose Triacetate. Cellulose triacetate (triethylcellulose) can interact stereoselectively with enantiomers of chiral drugs [48-50]. It has regions of crystallinity, which allow for enantioselective inclusion of drugs (solutes), especially those having substituent-free phenyl groups. However, it loses its enantioselectivity when solubilized and reprecipitated owing to the breakdown of the crystalline structure. 

Kim, K.H. Park, Y.H. Enantioselective inclusion between terbutaline enantiomers and hydroxypropyl-P-cyclodextrin. Int. J. Pharm. 1998, 175 (1),... 

Fig. 10. Constitutions of brucine (22) and sparteine (23) which are useful for enantioselective inclusion crystallization. The diagram shows the crystal packing of a corresponding clathrate of 22 [guest molecule being 3-(2-bromophenyl)-3-phenyl-l-propyne-3-ol, and is shaded] ...

Canceill. J. Lacombe, L. Collet. A. Analytical optical resolution of bromochlorofluoromethane by enantioselective inclusion into a tailor-made cryptophane and determination of its maximum rotation. J. Am. Chem. Soc. 1985. 107 (24). 6993-6996. 

Bile salts are chiral rigid molecules. They serve as important building blocks in the synthesis of both cyclic and acyclic hosts." " Natural bile acids are employed for enantioseparation of racemates of various classes of organic compounds by enantioselective inclusion complex-ation in the solid state." " " Crystals of bile acids contain... 

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