Atoms, chiral

Fischer projection A method of representing three-dimensional structures in two-dimensional drawings in which the chiral atom(s) lies in the plane of the paper. The two enantiomeric forms of glyceraldehyde are represented as... 

Chiral carbon atoms are common, but they are not the only possible centers of chirality. Other possible chiral tetravalent atoms are Si, Ge, Sn, N, S, and P, while potential trivalent chiral atoms, in which non-bonding electrons occupy the position of the fourth ligand, are N, P, As, Sb, S, Se, and Te. Furthermore, a center of chirality does not even have to be an atom, as shown in the structure represented in Figure 2-70b, where the center of chirality is at the center of the achiral skeleton of adamantane. 

In chemoinformatics, chirality is taken into account by many structural representation schemes, in order that a specific enantiomer can be imambiguously specified. A challenging task is the automatic detection of chirality in a molecular structure, which was solved for the case of chiral atoms, but not for chirality arising from other stereogenic units. Beyond labeling, quantitative descriptors of molecular chirahty are required for the prediction of chiral properties such as biological activity or enantioselectivity in chemical reactions) from the molecular structure. These descriptors, and how chemoinformatics can be used to automatically detect, specify, and represent molecular chirality, are described in more detail in Chapter 8. 

Clearly, the next step is the handling of a molecule as a real object with a spatial extension in 3D space. Quite often this is also a mandatory step, because in most cases the 3D structure of a molecule is closely related to a large variety of physical, chemical, and biological properties. In addition, the fundamental importance of an unambiguous definition of stereochemistry becomes obvious, if the 3D structure of a molecule needs to be derived from its chemical graph. The moleofles of stereoisomeric compounds differ in their spatial features and often exhibit quite different properties. Therefore, stereochemical information should always be taken into ac-count if chiral atom centers are present in a chemical structure. 

Multiple Chiral Centers. The number of stereoisomers increases rapidly with an increase in the number of chiral centers in a molecule. A molecule possessing two chiral atoms should have four optical isomers, that is, four structures consisting of two pairs of enantiomers. However, if a compound has two chiral centers but both centers have the same four substituents attached, the total number of isomers is three rather than four. One isomer of such a compound is not chiral because it is identical with its mirror image it has an internal mirror plane. This is an example of a diaster-eomer. The achiral structure is denoted as a meso compound. Diastereomers have different physical and chemical properties from the optically active enantiomers. Recognition of a plane of symmetry is usually the easiest way to detect a meso compound. The stereoisomers of tartaric acid are examples of compounds with multiple chiral centers (see Fig. 1.14), and one of its isomers is a meso compound. 

Difluorobutane contains two chiral atoms, and can exist as any one of three stereoisomers. Predicting the properties of these molecules is complicated due to the fact that each exists as a mixture of three conformers because of rapid internal rotation about the central carbon-carbon bond. 

What are the configurations (R or S) of the chiral carbons in each stereoisomer Does internal rotation affect the configuration of a chiral atom Why or why not ... 

Examine the geometry of 3-methyl-3-hexyl bromide, and assign the configuration (R or S) to the chiral atom. Examine the geometry of 3-methyl-3-hexyl cation. Is it chiral ... 

Aspartame is a dipeptide, made up of aspartic acid and phenylalanine. Identify all the chiral atoms in aspartame and assign R/S stereochemistry to each. Is the stereochemistry the same as in the natural forms of aspartic acid andphenylalaninel... 

Chart I. Trivial names (with recommended three-letter abbreviations in parentheses) and structures (in the aldehydic, acyclic form) of the aldoses with three to six carbon atoms. Only the D-forms are shown the L-forms are the mirror images. The chains of chiral atoms delineated in bold face correspond to the configurational prefixes given in italics below the names... 

A molecule that contains just one chiral carbon atom (defined as a carbon atom connected to four different groups also called an asymmetric or stereogenic carbon atom) is always chiral, and hence optically active. As seen in Figure 4.1, such a molecule cannot have a plane of symmetry, whatever the identity of W, X, Y, and Z, as long as they are all different. However, the presence of a chiral carbon is neither a necessary nor a sufficient condition for optical activity, since optical activity may be present in molecules with no chiral atom and since some molecules with two or more chiral carbon atoms are superimposable on their mirror images, and hence inactive. Examples of such compounds will be discussed subsequently. 

Compounds With Other Quadrivalent Chiral Atoms. Any molecule containing an atom that has four bonds pointing to the comers of a tetrahedron will be optically active if the four groups are different. Among atoms in this... 

Compounds With Tervalent Chiral Atoms. Atoms with pyramidal bonding might be expected to give rise to optical activity if the atom is connected to three different groups, since the unshared pair of electrons is analogous to a fourth group, necessarily different from the others. For example, a secondary or tertiary amine where X, Y, and Z are different would be expected to be chiral and thus resolvable. Many attempts have been made to resolve such compounds, but until 1968 all of them failed because of pyramidal inversion, which is a rapid oscillation of the unshared pair from one side of the XYZ... 

With these restrictions Fischer projections may be used instead of models to test whether a molecule containing asymmetric carbons is superimposable on its mirror image. However, there are no such conventions for molecules whose chirality arises from anything other than chiral atoms when such molecules are examined on paper, three-dimensional pictures must be used. With models or three-dimensional pictures there are no restrictions about the plane of the paper. 

The Cahn-Ingold-Prelog system is unambiguous and easily applicable in most cases. Whether to call an enantiomer (R) or (S) does not depend on correlations, but the configuration must be known before the system can be applied, and this does depend on correlations. The Cahn-Ingold-Prelog system has also been extended to chiral compounds that do not contain chiral atoms.A series of new rules have been proposed to address the few cases where the rules can be ambiguous, as in cyclophanes and other systems. ... 

Although four is the maximum possible number of isomers when the compound has two chiral centers (chiral compounds without a chiral carbon, or with one chiral carbon and another type of chiral center, also follow the rules described here), some compounds have fewer. When the three groups on one chiral atom are the same as those on the other, one of the isomers (called a meso form) has a plane of symmetry, and hence is optically inactive, even though it has two chiral carbons. Tartaric acid is a typical case. There are only three isomers of tartaric acid a pair of enantiomers and an inactive meso form. For compounds that have two chiral atoms, meso forms are found only where the four groups on one of the chiral atoms are the same as those on the other chiral atom. 

For a discussion of these rules, as well as for a review of methods for establishing configurations of chiral compounds not containing chiral atoms, see Krow, G. Top. Stereochem., 1970, 5, 31. 

Several fall into the third category, not least because their synthesis presents challenging hurdles. The chiral characteristic encountered in P-chirogenic ligands is however extremely interesting given the direct binding of the chiral atoms to the metal atom. This factor eliminates potentially inefficient secondary trans-... 

The introduction of a second chiral atom in the system leads to a reduction in the mesogenic properties and only a monotropic chiral nematic transition is observed for compound 23. However, when this compound is cooled down from the isotropic liquid state at a cooling rate of 0.5 °Cmin , very unusual blue phases BP-III, BL-II and BP-I are observed in the range 103-88 °C. Blue phases usually require pitch values below 500 nm. Hence the pitch value of the cholesteric phase for 23 must be very short, suggesting that the packing of two chiral carbons forces a faster helical shift for successive molecules packed along the perpendicular to the director. 

Molecules with a planar coordination figure do not contain planar atoms . Further, tetrahedral atoms , chiral atoms etc. are nonsense. A minimum of four atoms is required for a chiral structure. 

The enantioselectivity is determined in an irreversible step after the chiral atom has been formed. Deuteration experiments have shown that styrene... 

The first examples of optically active acyclic alkyl dimethyl-amidosulfites 103 with sulfur as the sole chiral atom were prepared (149) according to the reaction sequence shown in Scheme 5 from achiral alcohols and (+)-a-phenylethyl isothiocyanate as an asymmetric reagent. Optically active amidothiosulfites 104 were also synthesized using the same approach (150). 

A polymer such as -[-CH=CH-CH(CH3)-CH2-hr which has two main-chain sites of stereoisomerism, may be atactic with respect to the double bond only, with respect to the chiral atom only or with respect to both centres of stereoisomerism. If there is a random distribution of equal numbers of units in which the double bond is cis and trans, the polymer is atactic with respect to the double bond, and if there is a random distribution of equal numbers of units containing the chiral atom in the two possible configurations, the polymer is atactic with respect to the chiral atom. The polymer is completely atactic when it contains, in a random distribution, equal numbers of the four possible configurational base units which have defined stereochemistry at both sites of stereoisomerism. 

With n dissimilar chiral atoms the number of stereoisomers is 2" and the number of racemic forms is 2" as illustrated below for 2-chloro-3-bromobutan.e (n = 2). The R,S configuration is shown next to... 

If = 2 and the two chiral atoms are identical in that each holds the same four different groups, there are only 3 stereoisomers, as illustrated for 2,3-dichlorobutane. 

Problem 5.25 (a) What is the necessary and sufficient condition for the existence of enantiomers (6) What is the necessary and sufficient condition for measurement of optical activity (c) Are all substances with chiral atoms optically active and resolvable (d) Are enantiomers possible in molecules that do not have chiral carbon atoms (e) Can a prochiral carbon ever be primary or tertiary (/) Can conformational enantiomers ever be resolved ... 

Problem 5.26 Select the chiral atoms in each of the following compounds ... 

Problem 5.28 Relative configurations of chiral atoms are sometimes established by using reactions in which there is no change in configuration because no bonds to the chiral atom are broken. Which of the following reactions can be used to establish relative configurations ... 

The deepwater stalked crinoid Gymnocrinus richeri contained the gymnochromes C (659) and D (660) and isogymnochrome D (661). These compounds have a helical chirality and chiral atoms in the sidechains give rise to isomers [524]. 

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