The Chirality Center

Mirror-image forms of chlorodifluoro-methane are superimposable on each other. Chlorodifluoromethane is achiral. 

The mirror images of bromochlorofluoromethane have the same constitution. That is, the atoms are connected in the same order. But they differ in the arrangement of their atoms in space they are stereoisomers. Stereoisomers that are related as an object and its nonsuperimposable mirror image are classified as enantiomers. The word enantiomer describes a particular relationship between two objects. One cannot look at a single molecule in isolation and ask if it is an enantiomer any more than one can look at an individual human being and ask, Ts that person a cousin Furthermore, just as an object has one, and only one, mirror image, a chiral molecule can have one, and only one, enantiomer. 

The surest test for chirality is a careful examination of mirror-image forms for superimposability. Working with models provides the best practice in dealing with molecules as three-dimensional objects and is strongly recommended. 

Bromochlorofluoromethane is a known compound, and samples selectively enriched in each enantiomer have been described in the chemical literature. In 1989 two chemists at Polytechnic University (Brooklyn, New York) described a method for the preparation of BrClFCH that is predominantly one enantiomer. 

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 example, C-2 is a chirality center in 2-butanol it bears H, OH, CH3, and CH3CH2 as its four different groups. By way of 

2-Butanol Chiral four different groups at C-2 2-Propanol Achiral two of the groups at C-2 are the same 

Sample Solution A carbon with four different groups attached to it is a chirality center, (a) In 2-bromopentane, C-2 satisfies this requirement, (b) None of the carbons in 3-bromopentane has four different substituents, and so none of its atoms is a chirality center.  

Molecules with chirality centers are very common, both as naturally occurring substances and as the products of chemical synthesis. (Carbons that are part of a double bond or a triple bond can t be chirality centers.)  

4-Ethyl-4-methyloctane (a chiral alkane) Linalool (a pleasant-smelling oil obtained from oranges) 

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A phase change takes place when one enantiomer is converted to its optical isomer. As illustrated in Figure 9, when the chiral center is a tetra-substituted carbon atom, the conversion of one enantiomer to the other is equivalent to the exchange of two electron pairs. This transformation is therefore phase inverting. 

Figure 2-69. The two enantiomers of lactic acid assignment of R and S configurations to the enantiomers of lactic acid after ranking the four ligands attached to the chiral center according to the Cl P rules (OH > COjH > Me > H).

The neighborhoods of the atoms directly bonded to tbe chiral center must be defined. The neighborhood of an atom A. dircetly bonded to the ehiral eenter, is dc-fned as the set of atoms whose distance (in number of bonds) to A is less than their distance to any of the other three atoms bonded to the chiral center (Figure 8-9. In cyclic structures different neighborhoods can overlap. 

Benzyl bromide can be converted into ethylbenzene (731) by the reaction of Me4Sn. The use of HMPA as a solvent is important. Overall inversion of configuration takes place at the chiral center of deuterated benzyl bro-mide[598]. The cyanomethyiation[599] and methoxymethyiation[600] of aromatic rings are carried out by the reaction of cyanomethyltributyltin (732) and methoxymethyltributyltin. 

Identify the substituents at the chirality center and rank them in order of decreasing precedence accord mg to the system described in Section 5 4 Precedence IS determined by atomic number working outward from the point of attachment at the chirality center... 

In order of decreasing precedence the four substitu ents attached to the chirality center of 2 butanol are... 

As represented in the wedge and dash drawing at the top of this table the molecule is already appro priately oriented Hydrogen is the lowest ranked atom attached to the chirality center and points away from us... 

The order of decreasing precedence is counterclockwise The configuration at the chirality center is S... 

Switching the positions of two groups in a Fischer projection reverses the config ration of the chirality center... 

Eleven chirality centers may seem like a lot but it is nowhere close to a world record It is a modest number when compared with the more than 100 chirality centers typ ical for most small proteins and the thousands of chirality centers present m nucleic acids A molecule that contains both chirality centers and double bonds has additional opportunities for stereoisomerism For example the configuration of the chirality center m 3 penten 2 ol may be either R or S and the double bond may be either E or Z There fore 3 penten 2 ol has four stereoisomers even though it has only one chirality center... 

Our discussion to this point has been limited to molecules m which the chirality center IS carbon Atoms other than carbon may also be chirality centers Silicon like carbon has a tetrahedral arrangement of bonds when it bears four substituents A large number of organosilicon compounds m which silicon bears four different groups have been resolved into their enantiomers... 

Section 7 16 Atoms other than carbon can be chirality centers Examples include those based on tetracoordmate silicon and Incoordinate sulfur as the chirality center In principle Incoordinate nitrogen can be a chirality center m compounds of the type N(x y z) where x y and z are different but inversion of the nitrogen pyramid is so fast that racemization occurs vrr tually instantly at room temperature... 

All the double bonds are cis and the absolute configuration of the chirality center is S Wnte a stereochemically accurate representation of ectocarpene... 

The same cannot be said about reactions with alkyl halides as substrates The conver Sion of optically active 2 octanol to the corresponding halide does involve a bond to the chirality center and so the optical purity and absolute configuration of the alkyl halide need to be independently established... 

The acyl group of the carboxylic acid acyl chloride or acid anhydride is trans ferred to the oxygen of the alcohol This fact is most clearly evident m the esterification of chiral alcohols where because none of the bonds to the chirality center is broken m the process retention of configuration is observed... 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achi ral enol or enolate ion The sp hybridized carbon that is the chirality center m the start mg ketone becomes sp hybridized m the enol or enolate Careful kinetic studies have established that the rate of loss of optical activity of sec butyl phenyl ketone is equal to Its rate of hydrogen-deuterium exchange its rate of brommation and its rate of lodma tion In each case the rate determining step is conversion of the starting ketone to the enol or enolate anion... 

None of the bonds to the chirality center is broken when hydroxide attacks the carbonyl group Had an 8 2 reaction occurred instead inversion of configuration at the chirality center would have taken place to give (8) (—) 1 phenylethyl alcohol... 

As shown for the aldotetroses an aldose belongs to the d or the l series accord mg to the configuration of the chirality center farthest removed from the aldehyde func tion Individual names such as erythrose and threose specify the particular arrangement of chirality centers within the molecule relative to each other Optical activities cannot be determined directly from the d and l prefixes As if furns ouf bofh d eryfhrose and D fhreose are levorofafory buf d glyceraldehyde is dexfrorofafory... 

Next translate the Fischer projection of l serine to a three dimensional represen tation and orient it so that the lowest ranked substituent at the chirality center IS directed away from you... 

Ammonia reacts with the ketone carbonyl group to give an mine (C=NH) which is then reduced to the amine function of the a ammo acid Both mine formation and reduc tion are enzyme catalyzed The reduced form of nicotinamide adenine diphosphonu cleotide (NADPH) is a coenzyme and acts as a reducing agent The step m which the mine is reduced is the one m which the chirality center is introduced and gives only L glutamic acid... 

Chiral Center. The chiral center, which is the chiral element most commonly met, is exemplified by an asymmetric carbon with a tetrahedral arrangement of ligands about the carbon. The ligands comprise four different atoms or groups. One ligand may be a lone pair of electrons another, a phantom atom of atomic number zero. This situation is encountered in sulfoxides or with a nitrogen atom. Lactic acid is an example of a molecule with an asymmetric (chiral) carbon. (See Fig. 1.13b.)... 

Double Fiiedel-Ciafts alkylation of configuiationally pure pyiocene (a substituted lactone) with aiomatics results in the formation of cycloalkylation product with retention of configuration at the chiral center (63). 

Tbe purpose of tbe bydroxyl group is to acbieve some hydrogen bonding with the nearby carbonyl group and therefore hinder the motion of the chiral center. Another way to achieve the chiral smectic Cphase is to add a chiral dopant to a smectic Chquid crystal. In order to achieve a material with fast switching times, a chiral compound with high spontaneous polarization is sometimes added to a mixture of low viscosity achiral smectic C compounds. These dopants sometimes possess Hquid crystal phases in pure form and sometimes do not. 

Chirahty at the phosphoms is an unavoidable problem in all phosphorothioate syntheses. The phosphoramidite method produces a mixture of both the and the diastereomers having a small excess of the isomer (53). Although some progress has been made in the chiral synthesis of dinucleoside phosphorothioates, low yields have limited the utility of these approaches. The chiral center may be eliminated by replacing the other, nonbridging oxygen with sulfur. Avoidance of the chirahty problem is one reason for the interest in phosphorodithioates. 

Fig. 1. Conformational representation of the piperidine ring of morphine (1) and analogues meperidine (7, R = H, R = COOC2H ) and alphaprodine (7, R = R = 0CC2H ). The chiral center of interest in stmcture (7) is starred (see text).

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