Chiral stereomer

Chiral centers, more than one, lljf Chiral stereomer, 69 Cholesterol, chirality in, 81 Cinnamaldehyde, 328 Cis-trans interconversion, 111 Cis-trans isomerism, in cyclic compounds, 163 Claisen condensation, 394 rearrangement, 439 Cleavage, oxidative, 117 Clemmensen reduction, 219, 311 Coenzyme A, 354 Collins reagent, 264 Collision frequency, 39 Configuration, 72 relative, 76 Conformation, 51 Conformational diastereomers, 78 enantiomers, 78 stereomers, 78... 

In contrast to enantiomers, the European Pharmacopoeia differentiates qualitatively and quantitatively between epimeric chiral stereomers. This seems fully justified as individual epimers significantly differ in their pharmacological potency and may be present in a drug in various proportions. 

Early work on the asymmetric Darzens reaction involved the condensation of aromatic aldehydes with phenacyl halides in the presence of a catalytic amount of bovine serum albumin. The reaction gave the corresponding epoxyketone with up to 62% ee.67 Ohkata et al.68 reported the asymmetric Darzens reaction of symmetric and dissymmetric ketones with (-)-8-phenylmenthyl a-chloroacetate as examples of a reagent-controlled asymmetric reaction (Scheme 8-29). When this (-)-8-phenyl menthol derivative was employed as a chiral auxiliary, Darzens reactions of acetone, pentan-3-one, cyclopentanone, cyclohexanone, or benzophenone with 86 in the presence of t-BuOK provided dia-stereomers of (2J ,3J )-glycidic ester 87 with diastereoselectivity ranging from 77% to 96%. 

The most important and widely used approach to chiral sulfoxides is the method developed by Andersen (5) based on the reaction between the diastereomerically pure (or strongly enriched in one dia-stereomer) menthyl arenesulfinates and Grignard reagents. The first stereospecific synthesis of optically active (+H7 )-ethyl p-tolyl sulfoxide 22 was accomplished in 1962 by Andersen (75) from (-)-(iS)-menthyl p-toluenesulfmate 45 and ethylmagnesium iodide. 

A chiral stereoisomer is not superimposable on its mirror image. It does not possess a plane or center of symmetry. The nonsuperimposable mirror images are called enantiomers. A mixture of equal numbers of molecules of each enantiomer is a racemic form (racemate). The conversion of an enantiomer into a racemic form is called racemization. Resolution is the separation of a racemic form into individual enantiomers. Stereomers which are not mirror images are called diastereomers. 

Problem 22.5 (a) How many chiral C s are there in a typical (i) aldohexose (C HijO ), (ii) 2-ketohexose (6) How many stereomers should an aldohexose have <... 

Stereoisomers that are not mirror images of each other are called dia-stereomers. Thus geometrical isomers (e.g., 5 and 6) are diastereomers, as are molecules that have two or more chiral centers but that are not enantiomers. For example, 7 and 8 are diastereomers of one another. 

The first method, resolution, is unattractive unless both enantiomers are useful in synthesis. In some cases, such as the resolution of dienecarboxylic acid derivatives mentioned earlier (via the phenylethyl-ammonium salt), the resolution is efficient and provides optically pure materials in good yield.39 60,63 In certain cases, the dienyliron complex can be treated with a chiral nucleophile to give a mixture of dia-stereomers which are separated and then reconverted to enantiomerically pure dienyl complex.64 An example of this method is the resolution of complex (27 Scheme 33), via the menthyl ethers (195) and... 

IfK2, kl9 k u and k2 had the same values as K 2, k u k l9 and k 2, then the optical purity of the product, RH, would be determined solely by the value of the diastereomeric equilibrium constant Kv If, however, the primed and unprimed constants were different, the final optical yield could be determined by both thermodynamic and kinetic factors, and in one extreme could result in the observation that the preferred enantiomer of the product originated in the minor dia-stereomer. Clearly, kinetic factors can be important since the steric interactions of the initial two diastereomers are different and these could affect the rate constants of the reaction. Moreover, the o--alkyl intermediate is chiral, as shown for one of the initial olefin diastereomers in Figure 4, and the rate of hydrogen addition and insertion... 

A. Ordentlich, D. Barak, C. Kronman, H.P. Benschop, L.P.A. De Jong, N. Ariel, R. Barak, Y. Segall, B. VelanandA. Shafferman, Exploring the active center of human acetylcholinesterase with stereomers of an organophosphorus inhibitor with two chiral centers, Biochemistry, 38, 3055-3066 (1991). 

Asymmetric Strecker amino acid synthesis Addition of cyanotrimethylsilane catalyzed by ZnCl2 to optically active aldimines formed from 2,3,4,6-tetrapivaloyl-3-D-galactopyranosylamine as the chiral auxiliary can result in either (R)- or (S)-a-aminonitriles, depending on the solvent. THF or isopropanol favors (R)-dia-stereomers, whereas CHC13 favors the (S)-diastereomers. 

Chiral complexes are a rewarding field of study for 13C-NMR investigations. The sensitivity of the 13C atoms to the local environment is usually sufficient to allow the resolution and identification of the individual dia-stereomers, and although the magnitude of the splitting may appear to provide no direct chemical information, their very observation does. 

Beyond the disrotatory or conrotatory stereochemical imperative which must accompany all Nazarov cyclizations there exists a secondary stereochemical feature. This feature arises because of the duality of allowed electrocyclization pathways. When the divinyl ketone is chiral the two pathways lead to dia-stereomers. The nature of the relationship between the newly created centers and preexisting centers depends upon the location of the cyclopentenone double bond. The placement of this double bond is established after the electrocyclization by proton loss from the cyclopentenyl cation (equation 5). Loss of H, H or in this instance generates three tautomeric products. The lack of control in this event is a drawback of the classical cyclization. Normally, the double bond occupies the most substituted position corresponding to a Saytzeff process. The issue of stereoselection with chiral divinyl ketones is iUustrated in Scheme 7. The sense of rotation is defined by clockwise (R) or counterclockwise (5) viewing down the C—O bond. Thus, depending on the placement of the double bond, the newly created center may be proximal or distal to the preexisting center. If = H the double bond must reside in a less substituted environment to establish stereoselectivity. 

In organic syntheses, good syn/anti diastereoselectivities are important, but it is crucial to use methods to obtain the syn or anti dia-stereomer in its enantiopure form. Panek and coworkers have developed chiral crotyl silanes such as ( S)-12 that show remarkable induced selectivities in crotylation reactions. ... 

Aromatic oxazolines such as (99 Scheme 10) have also been used as chiral nucleophiles. Additions to carbonyl compounds occur with only modest stereoselectivities. Hie highest ratio of dia-stereomers produced (64 36) occurs when acetophenone is used as substrate. A stericdly undemanding transition state probably accounts for these disappointing results. 

Virtually all of the synthetic applications of chiral dipole-stabilized organolithiums reported to date have the C— Li bond in an allylic or benzylic system. The most important consequence of this fact is that the two stereoisomers shown in Figure 3 can interconvert by pyramidal inversion. Therefore, the stereoselectivity of the deprotonation is irrelevant to the stereoselectivity as manifested in the product dia-stereomer ratio. The source of the selectivity in the organolithium alkylation step has not been determined. The available data do not permit a distinction between at least three possibilities thermodynamic control as determined by the equilibrating organolithium diastereomers, - kinetic control according to Curtin-Hammett kinetics,or increased carbon-lithium covalency at low temperature. ... 

The oxazoline moiety is a masked carboxyl group. A chiral oxazoline moiety attached to enamine 230 confers chirality to the double bond on reduction. Separation of the dia-stereomers followed by hydrolysis of the oxazoline moiety provide 3-amino-4,4-difluoro-or 3-amino-4,4,4-trifluorobutanoates 233 in enantiomerically pure forms (see Scheme 9.51) [79]. 

Stereoisomers can be classified into two types enantiomers and dia-stereomers. Enantiomers (mirror images) have identical physical and chemical properties and therefore are not separated on the conventional reversed-phase stationary phases. Their separation will not be discussed. Diastereomers are isomers which are not mirror images of the parent. They have slightly different physical and chemical properties and can often be separated on conventional stationary phases. There are two classes of diastereomers optically active isomers when the API has two or more stereocenters and non-optically active geometric isomers, such as cis-trans, syn-anti, etc. Stereoisomers of chiral molecules must be included in the peak set. 

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