Chirality tetrahedral molecules

Although not within the general coverage of this review, it is of interest to note the preparation of a series of trinuclear metal compounds which are chiral. Vahrenkamp, using an elimination reaction, has been able to prepare a series of tetrahedral molecules containing three different metal centers ... 

The distinction between the various configurations of monocentric, tetrahedral molecules is dependent on the ability to differentiate between all four ligands. In systems with more than one asymmetric C-atom these can be regarded as the chiral subunits of the total configuration. If there is sufficient flexibility one can expect 2n configurations with n different asymmetric C-atoms. If there are asymmetric C-atoms of the same kind, as in the isomers of tartaric acid, a lower number of distinguishable configurations is encountered. 

Although the mechanism of this reaction remains unknown, we can visualize how such amplification could occur by assuming that the chirality-amplifying molecule is a tetrahedral zincate that includes two of the chiral effector molecules as ligands. The scheme is illustrated by the reactions depicted in Fig. 11.4. 

Any object that cannot be superimposed on its mirror image is called chiral, that is, it has the property of being right-handed or left-handed. Molecules (or other objects) that are not chiral are described as being achiral, which is the opposite of chiral. Tetrahedral atoms with four nonidentical substituents, then, give rise to two stereoisomers. Such atoms are called stereogenic centers, sometimes shortened to stereocenters. An older term applied specifically to carbon is asymmetric carbon. 

Originally, the four atoms bound to a tetravalent carbon atom were thought to occupy the corners of a square. However, when four different atoms were bound to a carbon atom, the resulting molecules were found to be optically active. Will (a) the square planar molecule and/or (i>) a tetrahedral molecule adequately account for the chirality of this type of molecule Briefly justify your answer. 

Analogous definitions and designations apply to molecules containing a chiral centre and a prochiral tetrahedral or trigonal centre. The plane containing the chiral and prochiral centres is called a diastereo-zeroplane (Y. Izumi, 1977). 

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... 

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.)... 

Chiral separations are concerned with separating molecules that can exist as nonsupetimposable mirror images. Examples of these types of molecules, called enantiomers or optical isomers are illustrated in Figure 1. Although chirahty is often associated with compounds containing a tetrahedral carbon with four different substituents, other atoms, such as phosphoms or sulfur, may also be chiral. In addition, molecules containing a center of asymmetry, such as hexahehcene, tetrasubstituted adamantanes, and substituted aHenes or molecules with hindered rotation, such as some 2,2 disubstituted binaphthyls, may also be chiral. Compounds exhibiting a center of asymmetry are called atropisomers. An extensive review of stereochemistry may be found under Pharmaceuticals, Chiral. 

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

If a tetrahedral center in a molecule has two identical substituents, it is referred to as prochiral since, if either of the like substituents is converted to a different group, the tetrahedral center then becomes chiral. Consider glycerol the central carbon of glycerol is prochiral since replacing either of the —CH9OH groups would make the central carbon chiral. Nomenclature for prochiral centers is based on the (R,S) system (in Chapter 3). To name the otherwise identical substituents of a prochiral center, imagine... 

The most common cause of chirality is the presence of four different substituents bonded to a tetrahedral atom, but that atom doesn t necessarily have to be carbon. Nitrogen, phosphorus, and sulfur are all commonly encountered in organic molecules, and all can be chirality centers. We know, for instance, that trivalent nitrogen is tetrahedral, with its lone pair of electrons acting as the fourth "substituent" (Section 1.10). Is trivalent nitrogen chiral Does a compound such as ethylmethylamine exist as a pair of enantiomers ... 

As in organic chemistry, there are several sources of chirality at a metal center. As for an asymmetric carbon atom in an organic molecule, the coordination of the metal ion by four different monodentate hgands in a tetrahedral con-... 

The great majority of known chiral compounds are naturally occurring organic substances, their molecules having one or more asymmetrically substituted carbon atoms (stereogenic atoms). Chirality is present when a tetrahedrally coordinated atom has... 

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