Stereogenic centers

Relative stereochemistry Stereochemical relationship between two or more stereogenic centers within a molecule... 

The reaction of vinyloxiranes with malonate proceeds regio- and stereose-lectively. The reaction has been utilized for the introduction of a 15-hydroxy group in a steroid related to oogoniol (265)(156]. The oxirane 264 is the J-form and the attack of Pd(0) takes place from the o-side by inversion. Then the nucleophile comes from the /i-side. Thus overall reaction is sT -StM2 type, in the intramolecular reaction, the stereochemical information is transmitted to the newly formed stereogenic center. Thus the formation of the six-membered ring lactone 267 from 266 proceeded with overall retention of the stereochemistry, and was employed to control the stereochemistry of C-15 in the prostaglandin 268[157]. The method has also been employed to create the butenolide... 

Epimers (Section 25 21) Diastereomers that differ in configu ration at only one of their stereogenic centers... 

Thiol (Section 15 13) Compound of the type RSH or ArSH Th reo (Section 7 11) Term applied to the relative configuration of two stereogenic centers within a molecule The threo stereoisomer has like substituents on opposite sides of a Fischer projection... 

KDPG is a member of a yet unexplored group of aldolases that utilize pymvate or phosphoenol pymvate as the nucleophile in the aldol addition. They are quite tolerant of different electrophilic components and accept a large number of uimatural aldehydes (148). The reaction itself, however, is quite specific, generating a new stereogenic center at the C-4 position. 

As chemists proceeded to synthesize more complicated stmctures, they developed more satisfactory protective groups and more effective methods for the formation and cleavage of protected compounds. At first a tetrahydropyranyl acetal was prepared, by an acid-catalyzed reaction with dihydropyran, to protect a hydroxyl group. The acetal is readily cleaved by mild acid hydrolysis, but formation of this acetal introduces a new stereogenic center. Formation of the 4-methoxytetrahy-dropyranyl ketal eliminates this problem. 

The introduction of a THP ether onto a chiral molecule results in the formation of diastereomers because of the additional stereogenic center present in the tetrahy-dropyran ring (which can make the interpretation of NMR spectra somewhat troublesome at times). Even so, this is one of the most widely used protective groups employed in chemical synthesis because of its low cost, the ease of its installation, its general stability to most nonacidic reagents, and the ease with which it can be removed. 

In some cases the formation of a dioxolane or dioxan -can result in the generation of a new stereogenic center, either with complete selectivity or as a mixture of the two possible isomers. Since the new center is removed on deprotection, it should not seriously complicate the use of those protective groups that generate a new stereogenic center. 

The related 2-/-butyl derivative has also been prepared and used to advantage as a temporary protective group for the stereogenic center of amino acids during alkylations. ... 

The 2-alkyl derivatives have been prepared to protect the stereogenic center of the a-hydroxy acid during alkylations. ... 

Compounds in which one or more carbon atoms have four nonidentical substituents are the largest class of chiral molecules. Carbon atoms with four nonidentical ligands are referred to as asymmetric carbon atoms because the molecular environment at such a carbon atom possesses no element of symmetry. Asymmetric carbons are a specific example of a stereogenic center. A stereogenic center is any structural feature that gives rise to chirality in a molecule. 2-Butanol is an example of a chiral molecule and exists as two nonsuperimposable mirror images. Carbon-2 is a stereogenic center. 

There are a number of important kinds of stereogenic centers besides asymmetric carbon atoms. One example is furnished by sulfoxides with nonidentical substituents on sulfur. Sulfoxides are pyramidal and maintain dieir configuration at room temperature. Unsymmetrical sulfoxides are therefore chiral and exist as enantiomers. Sulfonium salts with three nonidentical ligands are also chiral as a result of their pyramidal shape. Some examples of chiral derivatives of sulfur are given in Scheme 2.1. 

When a stereogenic center is tricoordinate, as is the case for sulfoxides, sulfbnium salts, and phosphines, then a phantom atom of atomic number zero is taken to occupy... 

Diastereomers include all stereoisomers that are not related as an object and its mirror image. Consider the four structures in Fig. 2.3. These structures represent fee four stereoisomers of 2,3,4-trihydroxybutanal. The configurations of C-2 and C-3 are indicated. Each stereogenic center is designated J or 5 by application of the sequence rule. Each of the four structures is stereoisomeric wife respect to any of fee others. The 2R R and 25,35 isomers are enantiomeric, as are fee 2R, iS and 25,3J pair. The 21 ,35 isomer is diastereomeric wife fee 25,35 and 2R,3R isomers because they are stereoisomers but not enantiomers. Any given structure can have only one enantiomer. All other stereoisomers of feat molecule are diastereomeric. The relative configuration of diastereomeric molecules is fiequently specified using fee terms syn and anti. The molecules are represented as extended chains. Diastereomers wife substituents on the same side of the extended chain are syn stereoisomers, whereas those wife substituents on opposite sides are anti stereoisomers. 

Sometimes the terms erythro and threo are used to specify fee relative configuration of two adjacent stereogenic centers. The terms are derived fom fee sugars erythrose and threose. The terms were originally defined such feat a Fischer projection formula in which two adjacent substituents were on the same side was fee erythro isomer and feat in whidi the substituents were on opposite sides was the threo isomer. 

Fischer projection formulas can be used to represent molecules with several stereogenic centers and are commonly used for caibohydrates. For other types of structures, a more common practice is to draw the molecule in an extended conformation witii the main chain horizontal. In this arrangement, each tetrahedral caibon has two additional substituents, one facing out and one in. The orientation is specified widi solid wedged bonds for substituents facing out and with dashed bonds for substituents that point in. 

Since chirality is a property of a molecule as a whole, the specific juxtaposition of two or more stereogenic centers in a molecule may result in an achiral molecule. For example, there are three stereoisomers of tartaric acid (2,3-dihydroxybutanedioic acid). Two of these are chiral and optically active but the third is not. 

The reason that the third stereoisomer is achiral is that the substituents on the two asymmetric carbons are located with respect to each other in such a way that a molecular plane of symmetry exists. Compounds that incorporate asymmetric atoms but are nevertheless achiral are called meso forms. This situation occurs whenever pairs of stereogenic centers are disposed in the molecule in such a way as to create a plane of symmetry. A... 

Incorporation of stereogenic centers into cyclic structures produces special stereochemical circumstances. Except in the case of cyclopropane, the lowest-eneigy conformation of the tings is not planar. Most cyclohexane derivatives adopt a chair conformation. For example, the two conformers of cis-l,2-dimethylcyclohexane are both chiral. However, the two conformers are enantiomeric so the conformational change leads to racemization. Because the barrier to this conformational change is low (lOkcal/mol), the two enantiomers arc rapidly interconverted. 

Preparation of enantiomerically enriched materials by use of chiral catalysts is also based on differences in transition-state energies. While the reactant is part of a complex or intermediate containing a chiral catalyst, it is in a chiral environment. The intermediates and complexes containing each enantiomeric reactant and a homochiral catalyst are diastereomeric and differ in energy. This energy difference can then control selection between the stereoisomeric products of the reaction. If the reaction creates a new stereogenic center in the reactant molecule, there can be a preference for formation of one enantiomer over the other. 

The addition of methylmagnesium iodide to 2-phenylpropanal is stereoselective in producing twice as much syn-3-phenyl-2-butanol as the anti isomer (entry 5). The stereoselective formation of a particular configuration at a new stereogenic center in a reaction of a chiral reactant is called asymmetric induction. This particular case is one in which the stereochemistry can be predicted on the basis of an empirical correlation called Cram s rule. The structural and mechanistic basis of Cramls rule will be discussed in Chapter 3. 

Similarly, the two faces at a trigonal earbon in a molecule containing a stereogenic center are diastereotopie. Both ehiral and achiral reactants can distinguish between these diastereotopie faces. Many examples of diastereotopie transformations of sueh eompounds are known. One of the cases that has been examined elosely is addition reactions at a trigonal center adjacent to an asymmetric carbon. Particular attention has been given to the case of nucleophilie addition to carbonyl groups. 

We will discuss the structural and mechanistic basis of Cram s rule in Chapter 3. As would probably be expected, the influence of a stereogenic center on the diastereoselec-tivity of the reaction is diminished when the center is more remote from the reaction site. 

Using the sequence rule, specify the configuration at each stereogenic center in the following molecules ... 

There have been many studies aimed at deducing the geometiy of radical sites by examining the stereochemistry of radical reactions. The most direct kind of study involves the generation of a radical at a carbon which is a stereogenic center. A planar or rapidly inverting radical would lead to racemization, whereas a rigid pyramidal structure should... 

Further evidence for a bromine-bridged radical comes from radical substitution of optically active 2-bromobutane. Most of the 2,3-dibromobutane which is formed is racemic, indicating that the stereogenic center is involved in the reaction. A bridged intermediate that can react at either carbon can explain the racemization. When the 3-deuterated reagent is used, it can be shown that the hydrogen (or deuterium) that is abstracted is replaced by bromine with retention of stereochemistry These results are also consistent with a bridged bromine radical. 

Chirality center (Section 7.2) An atom that has four nonequivalent atoms or groups attached to it. At various times chirality centers have been called asymmetric centers or stereogenic centers. 

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