Carbon chiral

In certain crystals, e.g. in quartz, there is chirality in the crystal structure. Molecular chirality is possible in compounds which have no chiral carbon atoms and yet possess non-superimposable mirror image structures. Restricted rotation about the C=C = C bonds in an allene abC = C = Cba causes chirality and the existence of two optically active forms (i)... 

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. 

Other methods have been proposed for detecting chiral carbon atoms which do not rely on the CIP system, and which have been more convenient for some specific applications [108]. 

Figure 8-10. C raphical representation of/dcciu) versus u for (-t-)-3 and (-)-3 sampled at 75 evenly distributed points between -0.03 A and + 0.03 e A b Hydrogen atoins not bonded to chiral carbon atoms were not considered.

The conformation-dependent chirality code constitutes a more general description of molecular chirality, which is formally comparable with the CICC [43], The main difference is that chiral carbon atoms arc now not explicitly considered, and combinations of any four atoms are now used, independently of the existence or nonexistence of chiial centers, and of their belonging or not belonging to ligands of chiral centers. 

The large sulfur atom is a preferred reaction site in synthetic intermediates to introduce chirality into a carbon compound. Thermal equilibrations of chiral sulfoxides are slow, and parbanions with lithium or sodium as counterions on a chiral carbon atom adjacent to a sulfoxide group maintain their chirality. The benzylic proton of chiral sulfoxides is removed stereoselectively by strong bases. The largest groups prefer the anti conformation, e.g. phenyl and oxygen in the first example, phenyl and rert-butyl in the second. Deprotonation occurs at the methylene group on the least hindered site adjacent to the unshared electron pair of the sulfur atom (R.R. Fraser, 1972 F. Montanari, 1975). 

Open-chain 1,5-polyenes (e.g. squalene) and some oxygenated derivatives are the biochemical precursors of cyclic terpenoids (e.g. steroids, carotenoids). The enzymic cyclization of squalene 2,3-oxide, which has one chiral carbon atom, to produce lanosterol introduces seven chiral centres in one totally stereoselective reaction. As a result, organic chemists have tried to ascertain, whether squalene or related olefinic systems could be induced to undergo similar stereoselective cyclizations in the absence of enzymes (W.S. Johnson, 1968, 1976). 

Recent syntheses of steroids apply efficient strategies in which open-chain or monocyclic educts with appropiate side-chains are stereoselectively cyclized in one step to a tri- or tetracyclic steroid precursor. These procedures mimic the biochemical synthesis scheme where acyclic, achiral squalene is first oxidized to a 2,3-epoxide containing one chiral carbon atom and then enzymatically cyclized to lanostetol with no less than seven asymmetric centres (W.S. Johnson, 1%8, 1976 E.E. van Tamden, 1968). 

Non-enzymatic cyclizations of educts containing chiral centres can lead to products with additional "asymmetric centres. The underlying effect is called "asymmetric induction . Its systematic exploration in steroid syntheses started when G. Saucy discovered in 1971 that a chiral carbon atom in a cyclic educt induces a stereoselective Torgov condensation several carbon atoms away (M. Rosenberger, 1971, 1972). 

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.)... 

FIGURE 1.13 Asymmetric (chiral) carbon in the lactic acid molecule. 

One of the newer and more fmitful developments in this area is asymmetric hydroboration giving chiral organoboranes, which can be transformed into chiral carbon compounds of high optical purity. Other new directions focus on catalytic hydroboration, asymmetric aHylboration, cross-coupling reactions, and appHcations in biomedical research. This article gives an account of the most important aspects of the hydroboration reaction and transformations of its products. For more detail, monographs and reviews are available (1—13). 

J. D. Morrison and J. W. ScoXt, Asymmetric Synthesis, Vol. 4, The Chiral Carbon Pool and Chiral Sulfur, Nitrogen, Phosphorus, and Silicon Centers, Academic Press, Inc., Odando, Fla., 1984. 

The steric bulk of the three iodine atoms in the 2,4,6-triiodoben2ene system and the amide nature of the 1,3,5-substituents yield rotational isomers of the 5-A/-acyl-substituted 2,4,6-triiodoisophthalamides. Rotational motion in the bonds connecting the side chains and the aromatic ring is restricted. These compounds also exhibit stereoisomerism when chiral carbon atoms are present on side chains. (R,5)-3-Amino-l,2-propanediol is incorporated in the synthesis of iohexol (11) and ioversol (12) and an (3)-2-hydroxypropanoyl group is used in the synthesis of iopamidol (10). Consequendy, the resulting products contain a mixture of stereoisomers, ie, meso-isomers, or an optical isomer. 

Appllca.tlons. The first widely appHcable Ic separation of enantiomeric metallocene compounds was demonstrated on P-CD bonded-phase columns. Thirteen enantiomeric derivatives of ferrocene, mthenocene, and osmocene were resolved (7). Retention data for several of these compounds are listed in Table 2, and Figure 2a shows the Ic separation of three metallocene enantiomeric pairs. P-Cyclodextrin bonded phases were used to resolve several racemic and diastereomeric 2,2-binaphthyldiyl crown ethers (9). These compounds do not contain a chiral carbon but stiU exist as enantiomers because of the staggered position of adjacent naphthyl rings, and a high degree of chiral recognition was attained for most of these compounds (9). 

Because a hexose contains four chiral carbon atoms, there are 2 = 16 different possible arrangements of the hydroxyl groups in space, ie, there are 16 different stereoisomers. The stmctures of half of these, the eight D isomers, are shown in Figure 1. Only three of these 16 stereoisomers are commonly found in nature D-glucose [50-99-7] D-galactose [59-23-4] and D-mannose [3458-28-4]. 

For the 1,2- and 3,4-addition, a chiral carbon (marked by an asterisk) is formed which has an R or 3 configuration, but there is no net optical activity, because equal amounts of the R and S configurations are formed. The R and S configurations along the polymer chains lead to diastereomeric isomers called isotactic, syndiotactic, and atactic. In isotactic polyisoprene all monomer units have the same configuration as illustrated for isotactic... 

The stereochemistry of hydrogen-deuterium exchange at the chiral carbon in 2-phenylbutane shows a similar trend. When potassium t-butoxide is used as the base, the exchange occurs with retention of configuration in r-butanol, but racemization occurs in DMSO. The retention of configuration is visualized as occurring through an ion pair in which a solvent molecule coordinated to the metal ion acts as the proton donor... 

Scheme 12.2. Stereochemistry of Radical Reactions at Chiral Carbon...

The reaction of diethyl tartrate with sulfur tetrafluonde at 25 °C results in replacement of one hydroxyl group, whereas at 100 °C, both hydroxyl groups are replaced by fluonne to form a,a -difluorosuccinate [762] The stereochemical outcome of the fluonnation of tartrate esters is retention of configuration at one of the chiral carbon atoms and inversion of configuration at the second chiral center [163,164, 165] Thus, treatment ofdimethyl(+)-L-tartrate with sulfur tetrafluonde gives dimethyl meso-a,a difluorosuccinate as the final product [163, 164], whereas dimethyl meso tartrate is converted into a racemic mixture of D- and L-a,a -difluorosuccmates [765] (equation 80)... 

FIGURE 4.12 Enantiomeric molecules based on a chiral carbon atom. Enantiomers are nonsuperimposable mirror images of each other. 

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 ... 

An alkene activated by an electron-withdrawing group—often an acrylic ester 2 is used—can react with an aldehyde or ketone 1 in the presence of catalytic amounts of a tertiary amine, to yield an a-hydroxyalkylated product. This reaction, known as the Baylis-Hillman reaction, leads to the formation of useful multifunctional products, e.g. o -methylene-/3-hydroxy carbonyl compounds 3 with a chiral carbon center and various options for consecutive reactions. 

One consequence of tetrahedral geometry is that an amine with three different substituents on nitrogen is chiral, as we saw in Section 9.12. Unlike chiral carbon compounds, however, chiral amines can t usually be resolved because the two enantiomeric forms rapidly interconvert by a pyramidal inversion, much as an alkyl halide inverts in an Sfg2 reaction. Pyramidal inversion occurs by a momentary rehybridization of the nitrogen atom to planar, sp2 geometry, followed by rehybridization of the planar intermediate to tetrahedral, 5p3 geometry... 

Follow the steps in the text. (1) Assign priorities to the four substituents on the chiral carbon. (2) Manipulate the Fischer projection to place the group of lowest priority at the top by carrying out one of the allowed motions. (3) Determine the direction 1 —> 2 — 3 of the remaining three groups. 

Click Coached Problems for a self-study module on identifying chiral carbon centers. 

In the following structural formulas, locate each chiral carbon... 

As you can see from their structures, a- and /3-glucose have several chiral carbon atoms. Both isomers are optically active they are not enantiomers (mirror images of one another) because they differ in configuration only at carbon atom 1. As it happens, both a- and /3-glucose rotate the plane of polarized light to the right (clockwise). 

Identify the chiral carbon atoms in a carbohydrate or n-amino acid. 

How many chiral carbon atoms are there in a-glucose in fructose ... 

Figure 8.3 Examples of different biological effects of enantiomers. S and R refer to a particular system of nomenclature used to describe chiral carbon, (see Appendix A8.1)...

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