Chiral host molecule

X-Ray crystal structural studies32) (Fig. 13 and Scheme 8 which refers to the crystal structure) showed that one molecule of 93 is held in a fixed conformation determined by two hydrogen bonds and by neighboring host molecules which prevent free rotation about the CO—CO single bond in 93. Free rotation about this bond would enable the production of the two possible enantiomers. The fixed conformation of the guest molecule by the chiral host molecule causes the least molecular motion during the photocyclization reaction and the high enantioselectivity. 

Many optically active hypervalent chalcogen compounds, particularly sulfur compounds, have been synthesized and proposed as important key intermediates in various reactions of the chalcogen compounds.46 Since the synthesis of spirosulfurane by Kapovits and Kalman,47 many optically active spir-osulfuranes were isolated in the last decade. Spirosulfurane 28 was separated into enantiomers by kinetic resolution using a chiral host molecule and found to be optically stable by Drabowicz and Martin.48 Spirosulfurane 29 was separated into enantiomers by chromatographic method by Allenmark and Claeson, and characterized by chiroptical methods.49 Optically active... 

Stereoselective catalysis using biocatalysts (e.g. enzymes) and also of rationally designed small chiral molecules, deals essentially with the same principle the spatial and selective docking of guest molecules to a chiral host molecule to form complementary interactions to form reversible transient molecule associates (see the specific sections in this volume). The enantiomeric excess of a certain reaction and hence the result will be determined by the degree of chiral discrimination. Along the same theoretical lines the concepts of protein (enzyme, antibody, etc.) mimicks via imprinted" synthetic polymers should be mentioned and will be discussed further. 

Let us consider an N phase doped with BSMs, where BSMs interact with chiral host molecules. The interaction energy between left-handed bent-core conformation and the chiral host molecule f/LH is different from that between right-handed bent-core conformation and the same chiral host molecule t/RH- The nonzero difference AU = f/LH Crh induces finite ee in BSMs, resulting in increased chiral molecules in the system. At the same time, we have to consider the dilution effect. 

Finally, the difference of chirality enhancement in the N and SmC phases should be mentioned. As shown in Sect. 2.1, enhancement rate in SmC is about one order of magnitude larger than that in N. In the SmC chirality enhancement is attributed to two effects (1) the interaction between bent-core and chiral host molecules and (2) the coupling between ee, tilt, and spontaneous polarization. The latter effect is absent in the N phase and is an additional effect in SmC. Moreover, the chiral discrimination parameter AU is expected to be larger in SmC than in N because of a confined geometry, i.e., smectic layer. 

Enantioselective photocyclization of 2-(arylthio)-3-methylcyclohexan-l-ones (75) to dihydrobenzothiophene derivatives 77 was also achieved in inclusion crystals using chiral host molecules. Photoirradiation of the 1 1 inclusion crystals of 75g with (-)-12b as a water suspension gave the corresponding photocyclization product (+ )-m-77g of 82% ee in 83% yield. Similar photoirradiation of the... 

To date the chiral host molecules most frequently used are the cyclic amylose oligomers or cyclodextrins (Cy), and the work in homogeneous solutions parallels the work done where they are used as chiral stationary phases [5,27], Among the major reasons for the choice are the ready availability of the compounds in relatively high chemical and optical purity and the convenience of the complexation reactions ... 

Host-guest crystal Chiral host molecule Moderate-high enantiodifferentiation... 

It should be noted that the intriguing stereochemical properties of these spherand calixarenes are not yet entirely understood and hence, their potential as chiral host molecules is not yet fully developed. 

These epimers, readily obtained under various conditions (alkaline as well as slightly acidic) are stable in solution only in the absence of acids. With traces of TFA the optical rotation changes (to reach an equilibrium value) and the H NMR spectrum shows the appearance of a second set of signals, probably due to an acid-catalyzed epimerization, as shown in Figure 21. This clearly limits the use of compounds such as 109 or 114 as chiral host molecules. 

Molecular Recognition. 1,2-Diaminocyclohexane has been often used as a scaffold for the syntheses of chiral host molecules and artificial receptors. Most of the examples relevant to this field may be found in reference 1. 

Achiral molecules can crystallize in a chiral space group or form inclusion crystals of achiral guest and chiral host molecules in the absence of any external source of chirality.588-590 Irradiation of such solid-state samples may then generate optically pure compounds in high chemical yields. This type of asymmetric induction is introduced later in Special Topic 6.5 and Case Study 6.21. 

Kakiuchi has reviewed some recent advances in enantioselective (2 + 2)- and (2 + 4)-photocycloaddition reactions in solution. Particular attention is given to the use of chiral host molecules and chiral auxiliary groups. 

Enantioselective complexation between chiral host molecules and racemic guests was also achieved. One enantiomer of phenylethylammonium cation can be selectively complexed by optically pure i>A(binaphtho)-22-crown-6. The racemic ammonium salt, dissolved in water, and the chiral crown, dissolved in an immiscible solvent such as CHCI3, are shaken together. If one of the two diastereomeric complexes is favored, it can be detected (e.g., by NMR) or separated. When the chiral macrocycle is bound to a resin, a multi-plate, chiral organic separation is possible. 

As described above, calixarenes are capable of including small molecules in solution. It thus occurred to us that introduction of chiral substituents into calixarenes would be of great value for development of a new class of chiral host molecules. 

With the hope of obtaining such macrocycles, we tried to synthesize macrocyclic compounds having Troger base skeletons as chiral host molecules. ... 

Finally, compound 46 is one of a group of chiral host molecules (TADDOLs) devised by Toda and Tanaka and synthesized from tartaric acid. These were designed and employed as chiral agents for resolution experiments. Often hydrogen-bonded complexes, rather than coordina-toclathrates, are formed using TADDOLs. However, then-molecular structure is again an excellent illustration of just how ubiquitous the wheel-and-axle motif is in inclusion chemistry. 

Besides the use of chiral bases or catalysts in solution, a rather interesting and unique approach that belongs to the present category involves the utilization of inclusion complexes of the stabilized ylides [104]. In the solid state, an achiral stabilized ylide such as 190 is reacted with a symmetrically substituted prochiral cyclohexanone such as 189 in the presence of a chiral host molecule. The best result was obtained using the chiral host molecule 191, which gave the dissymmetric alkene 192 with up to 57% ee. 

One of the main reasons for the still increasing interest in calixarenes is their ability to act as host molecules, which is even more pronounced in suitable derivatives that are readily available using calixarenes as starting materials. One of the main features of naturally occurring host molecules is their capacity for enantioselec-tive recognition. Various attempts have therefore been made to obtain chiral host molecules based on calixarenes. 

The chirality of compounds like 1-3 is entirely based on the chirality of the derivatizing reagents. However, due to their nonplanar shape, calixarenes offer numerous additional possibilities for producing chiral host molecules, which are not based on a chiral subunit but on the absence of a plane of symmetry or an inversion center in the molecule as a whole. In other words, opening of the macrocyclic structure would lead to an achiral linear molecule. Below we attempt to present a systematic overview of such inherently chiral calixarenes. 

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