Molecules with More Than One Chiral Center

4 MOLECULES WITH MORE THAN ONE CHIRAL CENTER 

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. 

Structures VII and VIII are identical because rotating either one 180° in the plane of the paper makes is superposable with the other one. VII possesses a symmetry plane and is achiral. Achiral stereoisomers which have chiral centers are called meso. The meso structure is a diastereomer of either of the enantiomers. The meso structure with two chiral sites always has the (RS) configuration. 

Problem 5.18 For the stereoisomers of 3-iodo-2-butanol, (a) assign R and S configurations to C and C. (b) Indicate which are (i) enantiomers and (ii) diastereomers. (c) Will rotation about the C—C bond alter the configurations  

Consider 7.53 and its enantiomer ent-7.53. These are clearly related as object and mirror image and, in the enantiomer, chiraUty, is reversed at each of the two asymmetric carbon atoms. What is the relationship between these two molecules and the enantiomeric pair 7.54 and ent-7.54 Remembering what we said about stereoisomers at the start of the chapter, the relationship between 7.53 and 7.54 is that of diastereoisomers—all relationships that are not enantiomeric are diastereo-isomeric. Diastereoisomers are different compounds, with different chemical and physical properties. Enantiomers have the same physical properties other than their ability to rotate the plane of plane-polarized light and the same chemical reactivity unless they are reacting with a chiral reagent. 

The difference in physical properties of diastereoisomers suggests a route that we might use to separate enantiomers (a process described as resolution)—vte will convert them, by some reversible process, into separable diastereoisomers. If we consider the reduction of 7.55 using sodium borohydride (weTl meet this reaction in Chapter 14), the ketone is planar and can be approached from either face by Na[BHj. These approaches are equally likely, so the product obtained will be racemic. If this alcohol is then reacted with a chiral carboxylic acid (Equation 7.3), then two distinct esters will be formed, with R,R- and R,S-stereochemistries. The two esters are diastereoisomers, which may be separated by physical techniques. Once the esters have been separated, then they can be hydrolyzed to obtain the separated alcohols and recover the chiral acid  

Separations may also be accomplished using chiral biological reagents, such as enzymes. Most enzymes, since they are composed of chiral amino acids, will accept only one enantiomer of a molecule as their substrate. Thus, the enzyme hog kidney acylase hydrolyzes only the natural enantiomer of amides. We will develop this idea further in Chapter 15, when we consider the reactions of carboxylic acid derivatives in more detail. 

In Problem 7.6(b), we noted that CM-l,2-dibromocyclobutane was not a chiral compound, because it has a plane of symmetry. However, it does have two asymmetric carbon atoms, each substituted by four different groups, Br, H, CHj, and CHBr. There are many such compounds, called meso-compounds. If we consider 2,3-dibromobutane, 7.56, there are two chiral centers, and thus, there should, in principle, be 2, that is, 4, stereoisomers. However, the mirror images, 7.57, are actually identical, and the plane of symmetry should be obvious. Note that for this type of molecule, it is easiest to see if a compound is meso when it is drawn in an eclipsed sawhorse form. 7.58 and ent-7.58 are true enantiomers and not superimposable. Thus, for this compound, there are three, not four, distinguishable stereoisomers. 

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One final very important point Everything we have said in this section concerns molecules that have one and only one chirality center molecules with more than one chirality center may or may not be chiral Molecules that have more than one chirality center will be discussed m Sections 7 10 through 7 13... 

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. 

Molecules with More than One Chiral Center... 

Another system of specifying configuration around a chiral center is the RS system, which is used in the systematic nomenclature of organic chemistry and describes more precisely the configuration of molecules with more than one chiral center (see p. 18). 

Stereoisomers that are not enantiomers are called diastereoisomers. Three classes may be distinguished configurational, geometrical, and conformational isomers. Configurational diastereomers include molecules with more than one chiral center. Thus 2,3-dichlorobutane can exist in three configurationally... 

Molecules with More Than One Chiral Center. Diastereomers... 

Molecules with more than one chirality center can also exist as enantiomers, but only if the molecule is not superposable on its mirror image. (We shall discuss that situation later in Section 5.12.) For now we will focus on molecules having a single chirality center. 

An ability to find chirality centers in structural formulas will help us in recognizing molecules that are chiral, and that can exist as enantiomers. The presence of a single chirality center in a molecule guarantees that the molecule is chiral and that enantiomeric forms are possible. However, as we shall see in Section 5.12, there are molecules with more than one chirality center that are not chiral, and there are molecules that do not contain a chirality center that are chiral. 

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