Chiral molecules cyclic compounds

Cyclic compounds Depending on the type of substitution on a ring, the molecule can be chiral (optically active) or achiral (optically inactive). For example, 1,2-dichlorocyclohexane can exists as meso compounds (optically inactive) and enantiomers (optically active). If the two groups attached to the ring are different, i.e. no plane of symmetry, there will be four isomers. 

The four different groups attached to a chiral carbon can be different elements, isotopes, or functional groups, and chiral centers can be present in bodi open-chain molecules or cyclic compounds. The recognition of chirality and chiral centers in molecules is an important step in determining the numbers of stereoisomers that are possible for a given compound. 

Diastereoisomerism is encountered in a number of cases such as achiral molecules without asymmetric atoms, chiral molecules with several centers of chirality, and achiral molecules with several centers of chirality (meso forms). Such cases can be encountered in acyclic and cyclic molecules alike, but for the sake of clarity these two classes of compounds will be considered separately. 

Asymmetric pericyclic reaction represents one of the most straightforward protocols to access enantioenriched cyclic compounds and triggers continuing interest in organic synthesis. Fruitful results have been achieved by the catalysis of chiral metal complexes over the past decades [1], On the other hand, recently small organic molecules have also contributed a lot to this area owing to the rapid development of asymmetric organocatalysis [2]. 

Various di- and polysubstituted cyclic compounds provide other examples of molecules having planes of symmetry. Since chirality depends on configuration, not conformation, cyclic molecules can be represented as planar structures to facilitate recognition of symmetry elements. These planar structures clearly convey the cis and trans relationships between substituents. Scheme 2.1 gives some examples of both chiral and achiral dimethylcycloalkanes. Note that in several of the compounds there is both a center and a plane of symmetry. Either element of symmetry ensures that the molecule is achiral. 

These are the most bitter tasting of all terpenoid compounds, responsible for the acclaimed stomachic and tonic properties of herbs such as marrubiin in horehound, Marrubium vulgare (Lamiaceae), and calumbin from calnmba, Jatrorrhiza palmata (Berberidaceae). They occnr as acyclic, cyclic, bi- tri- and tetracyclic compounds (referring to the number of carbon rings present), while many are also lactones. Some are chiral molecules, indicated by the prefix ent —for enantiomers. 

When a molecule has two or more stereogenic (chiral) centers, there are a maximum of 2" stereoisomers, where n = the number of chiral centers. When a molecule has two or more chiral centers, diastereomers are possible. Diastereomer is the term for two or more stereoisomers that are not superimposable and not mirror images. A diastereomer that has symmetry such that its mirror image is superimposable is called a meso compound. If there is no symmetry, cyclic molecules can have enantiomers and diastereomers. If there is symmetry in one diastereomer, cyclic compounds can have meso compounds 23, 24, 25, 26, 27, 28, 29, 30, 48, 49, 59, 60, 62,63,67,68,69, 70, 71, 75, 78, 79. 

The enantioselective reduction of unsaturated alcohol derivatives has been applied to the synthesis of several biologically active compounds (Scheme 24.12). Warfarin (123, R=H) is an important anticoagulant that is normally prescribed as the racemate, despite the enantiomers having dissimilar pharmacological profiles. One of the earliest reported uses of DuPhos was in the development of a chiral switch for this bioactive molecule, facilitating the preparation of (R)- and (S)-warfarin [184]. Although attempted reduction of the parent hydroxycoumarin 122 (R=H) led to formation of an unreactive cyclic hemiketal, hydrogenation of the sodium salt proceeded smoothly with Rh-Et-DuPhos in 86-89% ee. 

Cyclodextrins (CDs) are cyclic and nonreducing oligosaccharides and obtained from starch. The structures and properties of these molecules were discussed in detail in Chapter 3. These molecules are soluble in aqueous mobile phases and, hence, most of the chiral resolution was carried out under the reversed-phase mode. Therefore, cyclodextrins were used frequently as CMPAs for the chiral resolution of a wide variety of racemic compounds. The nontoxicity, nonvolatile, poor UV absorbance, stability over a wide range of pHs, and inexpensive natures of cyclodextrins make them superb CMPAs. 

The NADP-dependent TBADH was used for the laboratory-scale preparation of several chiral aliphatic and cyclic hydroxy compounds by reduction of the corresponding ketones. For the regeneration of NADPH, this reduction reaction can be coupled with the TBADH catalyzed oxidation of isopropanol. For the reduction of some ketones it was observed that the reaction rate was increased in the presence of the regenerating substrate isopropanol, for instance in the presence of 0.2 v/v isopropanol, the reduction rate of butanone or pentanone was increased 3-4-fold [57], In some cases, the enantiomeric excess of the reduction reaction is not very high, especially when small molecules are converted, but also for compounds such as acetophenone [138]. 

The chiral discrimination in cyclic dimers and trimers of mono-substituted sulfoxides and thioperoxides (Scheme 3.21) has been studied by means of DFT (B3LYP/6-31+G ) and ab initio (MP2/6-311+G ) calculations [5]. In addition, the inter- and intramolecular proton transfer processes that interconvert these two classes of compounds have been considered for the isolated molecules and the clusters. These two classes of compounds present different kinds of chirality, while the sulfoxides show a stereogenic sulfur atom, the thioperoxides present axial chirality. 

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 ... 

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