Chiral centers, in molecules

Epimers differ in configuration about a single chiral center in molecules with more than one chiral center. Anomers are epimers in which the chiral site was formerly a carbonyl C. 

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. 

In response to this nomenclature dilemma, the Cahn-Ingold-Prelog (IUPAC, International Union of Pure and Applied Chemistry) system of nomenclature was developed and is now the standard mediod to specify the relative configuration of chiral centers in molecules. Each chiral center will have two possible mirror-image configurations, which are designated as eidter R or S. 

It is clear from the above examples that the presence of chiral centers in molecules leads to stereoisomers. There is another type of molecule which itself is chiral but has no chiral center. The molecular chirality arises from the presence of a screw axis in the molecule. Allenes and biphenyls are common examples of such compounds, and because they are chiral, they exist as enantiomers. 

Assigning RorS Configuration to Chirality Centers in Molecules... 

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. 

Noting the presence of one (but not more than one) chirality center is a simple, rapid way to determine if a molecule is chiral. For exanple, C-2 is a chirality center in... 

In this exfflTipIe, addition to the double bond of an alkene converted an achiral molecule to a chiral one. The general term for a structural feature, the alteration of which introduces a chirality center in a molecule, is prochiral. A chirality center is introduced when the double bond of propene reacts with a peroxy acid. The double bond is a prochiral structural unit, and we speak of the top and bottom faces of the double bond as prochiral faces. Because attack at one prochual face gives the enantiomer of the compound formed by attack at the other face, we classify the relationship between the two faces as enantiotopic. 

In writing Eischer projections of molecules with two chirality centers, the molecule is arranged in an eclipsed conformation for projection onto the page, as shown in Eigure 7.9. Again, horizontal lines in the projection represent bonds coming toward you vertical bonds point away. 

A molecule that contains both chirality centers and double bonds has additional opportunities for stereoisomerism. For example, the configuration of the chirality center in 3-penten-2-ol may be either R or S, and the double bond may be either E or Z. Therefore 3-penten-2-ol has four stereoisomers even though it has only one chirality center. 

Section 7.2 The most common kind of chiral molecule contains a carbon atom that bears four different atoms or groups. Such an atom is called a chirality center. Table 7.2 shows the enantiomers of 2-chlorobutane. C-2 is a chirality center in 2-chlorobutane. 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achiral enol or enolate ion. The 5/) -hybridized carbon that is the chirality center in the starting ketone becomes 5/) -hybridized in the enol or enolate. Careful kinetic studies have established that the rate of loss of optical activity of 5cc-butyl phenyl ketone is equal to its rate of hydrogen-deuterium exchange, its rate of bromination, and its rate of iodina-tion. In each case, the rate-detennining step is conversion of the starting ketone to the enol or enolate anion. 

The two stereoisomeric furanose forms of D-erythrose ae naned a-D-erythro-furanose and p-D-erythrofuranose. The prefixes a and p describe the relative configuration of the anorneric cabon. The configuration of the anorneric cabon is cornpaed with that of the highest numbered chirality center in the molecule—the one that determines whether the cabohydrate is d or l. Chemists use a simplified, informal version of the lUPAC rules for assigning a and p that holds for ca bohydrates up to and including hexoses. 

As discussed in CbapL 6, copper-mediated diasteteoselective addition and substitution reactions ate well studied metliods for the construction of chiral centers in organic molecules. Tlie development of coppet-mediated enantioselective substitution reactions, however, is still at an early stage. 

Thomsen Click Organic Interactive to practice identifying chirality centers in organic molecules. 

Detecting chirality centers in a complex molecule takes practice because it s not always immediately apparent that four different groups are bonded to a given carbon. The differences don t necessarily appear right next to the chirality center. For example, 5-bromodecane is a chiral molecule because four different groups are bonded to C5, the chirality center (marked with an asterisk). A butyl substituent is similar to a pentyl substituent but it isn t identical. The difference isn t apparent until four carbon atoms away from the chirality center, but there s still a difference. 

Problem 9.2 I Identify the chirality centers in the following molecules. Build molecular models if i you need help. 

Problem 9.9 Assign R or S configuration to the chirality center in each of the following molecules ... 

Assign R or 5 configuration to each chirality center in the following biological molecules ... 

A molecule such as CHQBrl, which exists in two different forms that are not superim-posable mirror images, is said to be chiral. The two different forms are referred to as enantiomers, or optical isomers. Any molecule in which four different groups are bonded to carbon will be chiral the carbon atom serves as a chiral center. Molecules may contain more than one chiral center, in which case there can be more than two enantiomers. 

Concerted cycloaddition reactions provide the most powerful way to stereospecific creations of new chiral centers in organic molecules. In a manner similar to the Diels-Alder reaction, a pair of diastereoisomers, the endo and exo isomers, can be formed (Eq. 8.45). The endo selectivity in the Diels-Alder arises from secondary 7I-orbital interactions, but this interaction is small in 1,3-dipolar cycloaddition. If alkenes, or 1,3-dipoles, contain a chiral center(s), the approach toward one of the faces of the alkene or the 1,3-dipole can be discriminated. Such selectivity is defined as diastereomeric excess (de). 

A chiral center in a molecule is carbon atom with four different atoms or groups of atoms attached to it. If a molecule has a chiral center, it is very likely to be non-superimposable on its mirror image. Compounds (a) and (d) have no chiral center. Compounds (b) and (c) each have one asymmetric carbon atom, also called a chiral center. 

In general, the aldol reaction of an aldehyde with metal enolate creates two new chiral centers in the product molecule, and this may lead to four possible stereoisomers 2a, 2b, 2c, and 2d (Scheme 3-2 and Fig. 3-1). 

This chapter has introduced the aldol and related allylation reactions of carbonyl compounds, the allylation of imine compounds, and Mannich-type reactions. Double asymmetric synthesis creates two chiral centers in one step and is regarded as one of the most efficient synthetic strategies in organic synthesis. The aldol and related reactions discussed in this chapter are very important reactions in organic synthesis because the reaction products constitute the backbone of many important antibiotics, anticancer drugs, and other bioactive molecules. Indeed, study of the aldol reaction is still actively pursued in order to improve reaction conditions, enhance stereoselectivity, and widen the scope of applicability of this type of reaction. 

The presence of more chiral centers in the reactant molecule exhibits a positive influence in diastereoselective synthesis. The conformation of the reactants mediates these syntheses. In addition, part of the molecules could exhibit steric or electronic effects which can amplify or diminish the diastereoselectivity. 

Since the commercial introduction of the P-CAC in 1999, several industrial applications have been shown to be transferable to the system. Moreover, users in the biopharmaceutical and foodstuff industry have seen their productivity increasing dramatically as a result of using the P-CAC technology. Furthermore, a P-CAC has been shown capable of continuously separating stereoisomers when using chiral stationary phases even when there is more than one chiral center in the desired molecule. Below some of the applications are described in more details. Others are proprietary and hence cannot be disclosed. 

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