Chiral Compounds without Asymmetric Atoms

We can draw two nonsuperimposable mirror images of the most stable chair conformation of froni--1,2-dibromocyclohexane with both bromines equatoriaL These structures cannot interconvert by ring-flips or other rotations about bonds, however. They are mirror-image isomers enantiomers. 

This molecule s chirality is more apparent when drawn in its most symmetric conformatioa Drawn flat, the two mirror-image structures of frnnA-1,2-dibromocyclohexane are still nonsuperimposable. This compound is inherently chiral, and no conformational changes can interconvert the two enantiomers. 

Make a model of each compound, draw it in its most symmetric conformation, and determine whether it is capable of showing optical activity. 

Star ( ) each asymmetric carbon atom, and compare your result from part (1) with the prediction you would make based on the asymmetric carbons. 

Consider the most symmetric accessible conformation. You can also consider the most stable conformation and see if it can interconvert with its mirror image. 

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Biological Discrimination of Enantiomers 189 5-6 Racemic Mixtures 191 5-7 Enantiomeric Excess and Optical Purity 192 5-8 Chirality of Conformationally Mobile Systems 193 5-9 Chiral Compounds without Asymmetric Atoms 195 5-10 Fischer Projections 197... 

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. 

Amino acids are characteristic examples of compounds with an asymmetric carbon atom, with the exception of glycine which, since its a-carbon carries two hydrogens, is often said to be without an asymmetric carbon atom. As a typical C(abc2) system, glycine can be used (Schafer et al. 1984G) to illustrate the conformationally dependent chirality of tetrahedral carbon atoms with two substituents of identical constitution. That is, in compounds containing the glycine residue, some conformations usually exist in which the a-carbon is asymmetric and others in which it is not. 

The way in which compounds with asymmetric carbon atoms are racemized is more complicated. One possibility would be for a tetrahedral chiral carbon attached to four groups to become planar and achiral without breaking any bonds. Theoretical calculations indicate that this is not a likely process for chiral tetravalent carbon but, as we will see, it does occur with chiral carbon and other chiral atoms that are attached to three groups ... 

A final example shows a process called desymmetrization (Figure 15.25). We start with a raeso-compound (remember this is a molecule that contains asymmetric carbon atoms but is not chiral, because it has a plane of symmetry) with two identical functional groups. Under enzymatic hydrolysis, only one of these reacts, so a chiral compound is produced, and all the material is used, without any need to recycle. The enzyme used in this reaction is electric eel acetylcholinesterase (EEAc). Pig liver esterase is also commonly used, as a relatively crude extract is inexpensive and gives good results. An example is shown in Figure 15.26, in the synthesis of 7 -mevalonolactone, important in the biosynthesis of terpenes and steroids. 

The corresponding thioether fnnctionalised NHC without a second chiral wingtip gronp bnt an asymmetric carbon atom in the thioether sidearm was also synthesised by Ros et al. [261], However, we will tnrn our attention towards a similar example from the same research gronp [262] where the NHC is pyrido[a] annulated [263], The synthesis is again rather facile and follows standard procedures (see Figure 4.86). The chiral thioether precursor compound is accessible as the alcohol and needs to be treated with tetrabromomethane and PPhj to generate the required primary alkyl bromide. 

A classical method for the preparation of enantiopure compounds is the resolution of racemate. However, it is much more effective to use the selective synthesis of the desired enantiopure substance via enantioselective approach. Stereoselective methods of synthesis have been widely developed in organic chemistry. The method of asymmetric synthesis has been known since the nineteenth century and asymmetric catalysis has witnessed an enormous amount of development in recent decades as shown in Chapter 3. In contrast, the asymmetric synthesis of coordination compounds has only recently become a subject of systematic investigation. This is no doubt related to the fact that the chirality of coordination compounds is a much more complex phenomenon than that of organic compounds, because of higher coordination and the multitude of possible central atoms. Furthermore, while in organic chemistry the chiral tetrahedral carbon centres can be prepared without racemization, in contrast T-4 metal centres are very often labile. In fact it is even difficult to prepare compounds with a metal centre coordinated to four different monodentate ligands, and thus the possibility of obtaining one enantiomer is excluded in most cases. 

Asymmetric versions of these reactions, in which a stereocenter adjacent to the phosphorus is created in a controlled fashion, have been also developed " These rely either on diastereoselective reactions involving optically active starting material (a carbonyl compound or a phosphite) or on chiral catalysis. The Pudovik reaction with enantiopure nucleophiles containing a chiral phosphorus atom was found to occur without epimerization however, this feature has not been exploited yet in the synthesis of natural products or their analogs. ... 

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