Nomenclature 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. 

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. 

The first three chapters constitute a review of bonding and an introduction to organic compounds. Functional groups are introduced. Resonance is covered extensively, and numerous examples are provided. Acid-base chemistry is discussed in Chapter 4, and this reaction is used to introduce many of the general features of reactions, including the effect of structure on reactivity. Nomenclature of all of the functional groups is covered in Chapters 5 and 12. In this edition, stereochemistry is covered in two chapters to break up the material Chapter 6 discusses cis trans isomers and conformations, and Chapter 7 addresses chiral molecules. 

A useful atlas of chiral molecules has appeared the major monoterpenoids of known absolute configuration are illustrated, with a literature coverage to the end of 1971.3 The reader should beware of printing errors e.g. (+)-/ -irone lacks a methyl group at C-2, (—)-(R)-a-cyclogeraniol lacks a double bond between C-2 and C-3, and (+)-S-carotene has only 39 carbon atoms (p. 131) carvotanacetone is incorrectly indexed and the nomenclature and presentation of thujane monoterpenoids is different from that used in these Reports. 

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... 

Therefore, an sp2 hybridized carbon bonded to three different groups will become chiral as the result of an addition reaction (which may also be a reduction) that results in formation of a bond between the sp2 hybridized carbon and a fourth group that differs from the other three. Such sp2 hybridized carbons are called prochiral. This raises an interesting point of nomenclature. A chiral molecule that has four different groups attached to a carbon atom is said to have a stereogenic centre, this term being preferred to chiral centre . However, a prochiral molecule is said to have a prochiral centre the term pro-stereogenic , preferred by Helmchen,2 is not yet widely adopted. 

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]. 

Photo 1.2) in 1874 that carbon atoms could be tetrahedral and that this led to mirror-image isomers (see Sidebar l.C). Most of the nomenclature associated with the naming of chiral molecules actually preceded knowledge of the absolute structure. In fact, the first determination of the absolute structure of a chiral molecule containing an as)anmetric carbon didn t occur until 1951 ... 

The CIP nomenclature has been applied to virtually all chiral molecules, such that chemists are able to communicate to each other the absolute structure of such species in an unambiguous... 

Many chiral molecules lack a conventional center that can be described by the R/S or E/Z nomenclature system. Typically these molecules can be viewed as helical, and they may have propeller, or screw-shaped, structures. For example, conformations of simple chain compounds can also be treated as if they had helical chirality. 

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