Host, chiral, inclusion

Enantioselective self-assembling of amino acids 209 Host-guest inclusion complexes 213 Reactivity of chiral ion-dipole complexes 233... 

Chiral recognition, see also Host-guest inclusion complexes... 

Host-guest inclusion complexes, 262—263 antibiotic hosts, 231—233 cahxarene hosts, 228—231 chiral crown ether hosts, 213—218 cyclic oligosaccharide hosts, 218—222 cyclodextrin host selectivities, 223/ host molecular size, 221 hnear ohgosaccharide hosts, 222—228 ir- TT stacking interactions, 217 proteic hosts, 231 Human 15-hpoxygenase, 52/... 

T. J. Ward, Chiral Separations, Anal. Chem. 2002, 74, 2863 J. Hern6ndez-Benito, M. P. Garda-Santos, E. O Brien, E. Calle, and J. Casado, A Practical Integrated Approach to Supramolecular Chemistry IE. Thermodynamics of Inclusion Phenomena, J. Chem. Ed. 2004, 81, 540 B. D. Wagner, P. J. MacDonald, and M. Wagner, Visual Demonstration of Supramolecular Chemistry Fluorescence Enhancement upon Host-Guest Inclusion, J. Chem. 

A special case of host-guest inclusion is the resolution of a racemic mixture of chiral guests. This has important implications for the pharmaceutical industry, where the production of enantiomerically pure drugs has recently become increasingly important. A common method of chiral resolution is via the formation and separation of diastereomers. For example, a racemic acid AH may be treated with a chiral base B [21] ... 

Toda, F., Tanaka, K., Matsumoto, T., Nakai, T., Miyahara, I., and Hirotsu, K. (2000) A New Host 2,3,6,7,10,11-Hexahydroxytriphenylene Which Forms Chiral Inclusion Crystalline Lattice X-ray Structural Study of the Chiral Crystalline Lattice, J. Phys. Org. Chem., 13, 39-45. 

Tanaka, K., Moriyama, A., and Toda, F. (1997) Novel Chiral Recognition in Host-Guest Inclusion Complexes Depending on Their Molar Ratios Efficient Resolution of 2,2 -Dihydroxy-1,1 -binaphthyl Derivatives and CD Spectral Study of Inclusion Complex Crystals, J. Org. Chem., 62, 1192-1193. 

HOST-GUEST INCLUSION COMPLEXES Chiral crown ether hosts... 

An inclusion compound is composed of two or more distinct molecules held together by noncovalent forces in a definable structural relationship. Chiral inclusion complexes have been used by the groups of Lahav, Leisorowitz, and Toda to carry out asymmetric photoreactions [208-245]. The chirality of the host... 

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. 

While these chiral host-guest inclusion compounds have been demonstrated to produce excellent ee s it has proven difficult to predict in an apriori fashion the direction of enantiomeric preference. For example in the cyclization reaction of 21, host 16b produces one enantiomer in 98% ee while 16c produces the opposite enamtioner with 95% ee. It should be noted that 16b and 16c are rather similar and it is therefore difficult without further work to ascribe the exact cause for the different product outcome. ... 

Scheme 2. Preparation of chiral - 01 (S j-2,2 -bis(diphenyphosphino)-1,1 -binaphthyl.

It is essential that no covalent bonds are formed between host and guest molecules, as, e.g., when diastereomeric salts are used for separation. The differentiation of the enantiomers is effected only by the chiral (spatial) environment in the crystal or in the interior of the host molecule, respectively, whereby hydrogen bridges and dipol-dipol interactions may increase the stability of the inclusion compounds ( coordinato-clathrates ). The different energy constants of the diastereomeric host/guest inclusion compounds which result, e.g., in different solubilities, can be used to isolate one of the enantiomers. 

Similarly, 6°-metacyclophane forms clathrate complexes with benzene derivatives or alicyclic compounds, where only a little guest selectivity has been found ) The ratio n/m of these crystal lattice (cavity) inclusion compounds varies significantly, e.g., n/m=0.3-0.6 (cyclotricatechylene), 2-6 (tri-O-thymotide). It has been found that tri-O-thymotide resolves optical isomers, e.g., 2-butyl halides, by making host-guest inclusion crystals. These optical resolutions are therefore attributable to the crystal lattice chirality that was induced... 

A different non-classical approach to the resolution of sulphoxides was reported by Mikolajczyk and Drabowicz269-281. It is based on the fact that sulphinyl compounds very easily form inclusion complexes with /1-cyclodextrin. Since /1-cyclodextrin as the host molecule is chiral, its inclusion complexes with racemic guest substances used in an excess are mixtures of diastereoisomers that should be formed in unequal amounts. In this way a series of alkyl phenyl, alkyl p-tolyl and alkyl benzyl sulphoxides has been resolved. However, the optical purities of the partially resolved sulphoxides do not exceed 22% after... 

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 caUed 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 (53) partially to resolve the racemic amine salt (54). " When an aqueous solution of 54 was... 

A regio- and stereoselective Beckmann rearrangement utilized diastereose-lective host guest interactions of the inclusion complexes 225 and 228 in a solid state reaction. Initially, a 1 1 mixture of the chiral host 223 and the racemic oximes 224 and 227, respectively, was treated with ultra sound in the solid state to induce the optical resolution. Then H2SO4 was added to start the Beckmann rearrangement, the corresponding c-caprolactams 226 and 229 were isolated in 68 % and 64 % yields and ee of about 80 % and 69 % (determined by HPLC analysis on chiracel OC) (Scheme 43) [46]. 

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. 

An enantioselective Michael addition reaction was also accomplished in an inclusion complex with a chiral host compound. Treatment of a 1 1 complex of 10c and 66b with 2-mercaptopyridine (137) in the solid state gave (+)-138 of 80% ee in 51% yield. By a similar method, 3-methyl-3-buten-2-one (139) gave (+)-140 of 49% ee in 76% yield [30]. 

It is not easy to control the steric course of photoreactions in solution. Since molelcules are ordered regularly in a crystal, it is rather easy to control the reaction by carrying out the photoreaction in a crystal. However, molecules are not always arranged at an appropriate position for efficient and stereoselective reaction in their crystals. In these cases inclusion chemistry is a useful technique, as it can be employed to position molecules appropriately in the host-guest structure. Chiral host compounds are especially useful in placing prochiral and achiral molecules in suitable positions to yield the desired product upon photoirradiation. Some controls of the steric course of intramolecular and intermolelcular photoreactions in inclusion complexes with a host compound are described. 

Enantiocontrol of the photocyclization of Ar-methyl-AT-phenyl-3-amino-2-cyclohexen-l-one (151a,b) to the corresponding AT-methylhexahydro-4-car-bazolones (153a,b) via the dipolar ionic intermediate (152a,b) (Scheme 22) was also accomplished by photoirradiation of 1 1 inclusion complexes of 151 a,b with the chiral hosts lOa-c. Of the complexes prepared, 10a-151a, 10a-151b,... 

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