Nomenclature for Chiral Molecules

The discoveries of optical activity and enantiomeric structures (see the box, page 97) made it important to develop suitable nomenclature for chiral molecules. Two systems are in common use today the so-called d,l system and the (R,S) system. 

Aldoses with at least three carbons and ketoses with at least four carbons contain chiral centers (Chapter 4). The nomenclature for such molecules must specify the configuration about each asymmetric center, and drawings of these molecules must be based on a system that clearly specifies these configurations. 

This chapter has provided a general introduction to stereochemistry, the nomenclature for chiral systems, the determination of enantiomer composition and the determination of absolute configuration. As the focus of this volume is asymmetric synthesis, the coming chapters provide details of the asymmetric syntheses of different chiral molecules. 

Nomenclature of chemical compounds. Most undergraduate organic textbooks provide a more detailed account of die nomenclature used for organic molecules, including the R,S nomenclature for chiral centers. 

If a tetrahedral center in a molecule has two identical substituents, it is referred to as prochiral since, if either of the like substituents is converted to a different group, the tetrahedral center then becomes chiral. Consider glycerol the central carbon of glycerol is prochiral since replacing either of the —CH9OH groups would make the central carbon chiral. Nomenclature for prochiral centers is based on the (R,S) system (in Chapter 3). To name the otherwise identical substituents of a prochiral center, imagine... 

The nomenclature for biaryl, allene, or cyclohexane-type compounds follows a similar rule. Viewed along the axis, the nearer pair of ligands receives the first two positions in the order of preference, and the farther ligands take the third and fourth position. The nomination follows a set of rules similar to those applied in the central chiral system. In this nomination, the end from which the molecule is viewed makes no difference. From whichever end it is viewed, the positions remain the same. Thus, compound 7a has an ( -configuration irrespective of which end it is viewed from. 

A nomenclature system proposed for C6o derivatives, which is based on edge labeling of the icosahedron and allows even a configurational description of chiral molecules, does not appear to lead to a more intuitive operation cf. Nakamura, Y. Taki, M. Nishimura, J. Chem. Lett. 1995, 703-704. 

Although we have shown that 4 is chiral, and that it has no stereogenic centre, it is not without symmetry. This is best seen with the aid of a Newman projection of 4, which is shown in 5. A two-fold (C2) axis of symmetry exists as shown this passes through the central carbon, C(2), and bisects the right angle between the two chlorine atoms (and likewise the two hydrogen atoms). Rotation about this axis by 180° gives an identical molecule. Because of the axis of symmetry, 4 cannot be said to be asymmetric, and similar situations are found in certain other chiral molecules. This has had implications for stereochemical nomenclature. In particular, to avoid confusion the term asymmetric carbon is now little used even for an sp3 hybridized carbon that carries four... 

In all the listed amino acids, with the exception of glycine, the a-carbon is bound to four different substituents hence it is a stereogenic center. From this it follows that every amino acid can appear in the form of two enantiomers. In the following example, both the enantiomers of alanine are represented together with their absolute configurations. However, enantiomers of amino acids can also be represented by the traditional notation of chiral molecules that is called the relative configuration. This nomenclature for configuration was proposed Emil Fischer in the nineteenth century for the representation of the stereochemistry of carbohydrates. 

The International Union of Pure and Applied Chemistry (lUPAC) recommended in 2001 [10], that every Uquid crystalline phase composed of chiral molecules should be denoted with a superscript asterisk. However, this is not customary in lyotropic liquid crystal nomenclature, except for the chiral nematic phase (N ). Thus, for all other conventional lyotropic liquid crystalline phases the asterisk will be omitted. Whenever the chirality of the molecules seems to be especially important, the according phase will be denoted as chiral . 

As mentioned, the specific rotation is a physical property of the enantiomer. One enantiomer will have a specific rotation with a clockwise rotation (+) and the other enantiomer will have a specific rotation with counterclockwise rotation (-). 2-Butanol has two enantiomers. One has a [a] of +13° (neat) and is named (+)-2-butanol. The term neat refers to the fact that no solvent is used and pure 2-butanol is placed in the polarimeter cell to measure a. The other enantiomer is (-)-2-butanol with [a], -13° (neat) and it may be called ent-2-butanol, where ent means enantiomer. The ent nomenclature is usually applied to more complicated chiral molecules, and it will rarely be used in this book. As with this example, enantiomers will have the same magnitude for specific rotation, but they will have the opposite sign [(+) or (-)]. 

In the course of retrosynthetic consideration of TM 1, we completely neglected the stereochemistry. This is chiral molecule, and in praxis usually preparation of one enantiomer, denoted as asymmetric synthesis or synthesis of an enantiomerically pure compound, is targeted. When more stereogenic centers are present, expression of the asymmetric synthesis of an optically pure compound is preferred. Let as now assume that our target is (5)-TM 1 (for R, S nomenclature and CIP convention, see Sect. 3.1). 

Often symmetry operations cannot be used in a simple way to classify chiral forms because, e.g., the molecule consists of a number of conformations. Therefore, independent of the symmetry considerations, a chemical approach to describe chiral molecules has been introduced by the use of structural elements such as chiral centers, chiral axis, and chiral planes. Examples for a chiral center are the asymmetric carbon atom, i.e., a carbon atom with four different substituents or the asymmetric nitrogen atom where a free electron pair can be one of the four different substituents. A chiral axis exists with a biphenyl (Figure 3.2) and chiral planes are found with cyclo-phane structures [17]. Chiral elements were introduced originally to classify the absolute configuration of molecules within the R, S nomenclature [16]. In cases where the molecules are chiral as a whole, so-called inherent dissymmetric molecules, special names have often been introduced atropiso-mers, i.e., molecules with hindered rotation about a helical molecules [18], calixarenes, cyclophanes [17], dendrimers [19], and others [20]. 

A quick test for chirality is to look for the presence of an internal mirror plane. A molecule that lacks such a plane is most always chiral or optically active and is often designated by the R rectus, or right-handed)/ sinister, or left-handed) scheme of nomenclature. 

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