Achiral molecules diastereomeric

It is now possible to see why, as mentioned on p. 95, enantiomers react at different rates with other chiral molecules but at the same rate with achiral molecules. In the latter case, the activated complex formed from the R enantiomer and the other molecule is the mirror image of the activated complex formed from the S enantiomer and the other molecule. Since the two activated complexes are enantiomeric, their energies are the same and the rates of the reactions in which they are formed must be the same (see Chapter 6). However, when an R enantiomer reacts with a chiral molecule that has, say, the R configuration, the activated complex has two chiral centers with configurations R and R, while the activated complex formed from the S enantiomer has the configurations S and R. The two activated complexes are diastereomeric, do not have the same energies, and consequently are formed at different rates. 

As a unichiral group which reacts with the racemate to form diastereomeric molecules which can be separated by achiral adsorption processes. 

A closely related method does not require conversion of enantiomers to diastereomers but relies on the fact that (in principle, at least) enantiomers have different NMR spectra in a chiral solvent, or when mixed with a chiral molecule (in which case transient diastereomeric species may form). In such cases, the peaks may be separated enough to permit the proportions of enantiomers to be determined from their intensities. Another variation, which gives better results in many cases, is to use an achiral solvent but with the addition of a chiral lanthanide shift reagent such as tris[3-trifiuoroacetyl-Lanthanide shift reagents have the property of spreading NMR peaks of compounds with which they can form coordination compounds, for examples, alcohols, carbonyl compounds, amines, and so on. Chiral lanthanide shift reagents shift the peaks of the two enantiomers of many such compounds to different extents. 

Diastereoisomeric transition states calculated for propene primary insertion in a model of the Ewen achiral metallocenes are shown in Figure 1.20. The two possible diastereomeric transition states correspond to si (Figure 1.20a) and re (Figure 1.20b) insertions of the monomer for the case of a si chain (i.e., a growing chain in which the last monomeric unit has been obtained by a cis addition of a -coordinated monomer molecule) and are suitable for like (isotactic) and unlike (syndiotactic) propagations, respectively.142,143... 

Asymmetric synthesis is a term first used in 1894 by E. Fischer and defined4 in 1904 by W. Markwald as a reaction which produces optically active substances from symmetrically constituted compounds with the intermediate use of optically active materials but with the exclusion of all analytical processes . A modem definition was proposed 5) by Morrison and Mosher An asymmetric synthesis is a reaction in which an achiral unit in an ensemble of substrate molecules is converted by a reactant into a chiral unit in such a manner that the stereosiomeric products (enantiomeric or diastereomeric) are formed in unequal amounts. This is to say, an asymmetric synthesis is a process which converts a prochiral6) unit into a chiral unit so that unequal amounts of stereoisomeric products result . When a prochiral molecule... 

Biopolymers in Chiral Chromatography. Biopolymers have had a tremendous impact on the separation of nonsupernnposable. mirror-image isomers known as enantiomers. Enantiomers have identical physical and chemical properties in an achiral environment except that they rotate the plane of polarized light in opposite directions. Thus separation of enantiomers by chromatographic techniques presents special problems. Direct chiral resolution by liquid chromatography (lc) involves diastereomenc interactions between the chiral solute and the chiral stationary phase. Because biopolymers are chiral molecules and can form diastereomeric... 

On the other hand, the association of two enantiomeric components yields an achiral supermolecule of meso type this may occur through a symmetrical bridging molecule in order to take care of the identical interaction sites at symmetry-related positions, as shown in the three-component supermolecule 187a the corresponding diastereomeric DL pair may also be obtained (see 187b). Thus, achiral components can associate into a chiral supermolecule and chiral components can give an achiral supermolecule. 

HPLC-CSPs are based on molecules of known stereochemical composition immobilized on liquid chromatographic supports. Single enantiomorphs, diastereomers, diastereomeric mixtures, and chiral polymers (such as proteins) have been used as the chiral selector. The chiral recognition mechanisms operating on these phases are the result of the formation of temporary diastereomeric complexes between the enantiomeric solute molecules and immobilized chiral selector. The difference in energy between the resulting diastereomeric solute/CSP complexes determines the magnitude of the observed stereoselectivity, whereas the sum total of the interactions between the solute and CSP chiral and achiral, determines the observed retention and efficiency. 

An interesting example taking the opposite approach was presented by Wieczorek et al. [24]. To separate a mixture of dipeptide diastereoisomers and their phosphonic analogues, achiral crown ethers were used as transport enhancers. In this case, the diastereomeric complex is formed between the chiral transported molecule and not the optically active carrier. The observed stereoselectivity depends on the peptide structure and was independent of the presence of carrier, but the application of carrier increased the transport rate of both diastereoisomers. 

For characterization and exploitation of the diamide-phase system, a chiral diamide, e,g., (Ill) was examined as a modifier in the mobile phase (solvent) in conjunction with a non-bonded (bare) silica. Such a chiral carrier separated enantiomeric N-acyl-d-amino acid esters and amides with separation factors comparable to those for bonded stationary phase systems. The resolution can be as cribed to diastereomeric complexation through amide-amide hydrogen bonding between the amide additive and enantiomeric solute molecules in the carrier solvent, followed by separation of the diastereomeric complexes by the (achiral) silica phase. This process should be applicable as widely as that involving chiral diamide-bonded stationary phase systems. 

The aldol condensation is a powerful tool for the stereoselective synthesis of acyclic molecules with contiguous chiral centers. The catalytic asymmetric aldol reaction of ( )-2-rerr-butyldimethylsiloxy-2-phenylacetaldehyde (121) with the achiral silyl enol ether 1-ethylthio-l-trimethylsilyloxyethene (134) in the presence of tin(II) trifluoride and the chiral promotor ( S)-l-methyl-2-[(7V-naphthylamino)methyl]pyrrolidine (135) in propionitrile at — 78 °C proceeds smoothly to give a 94 6 mixture of diastereomeric aldol adducts 136 and 137 in 85% yield (Scheme 32). When performed on ( S)-129 this same reaction affords in 85% yield a 96 4 mixture of diastereomers 138 and 139. It is noteworthy that the newly created chiral centers in both of the major diastereomers 136 and 138 has the S configuration, suggesting that the stereochemistry of the aldol reaction is controlled by the chiral promotor and not the chiral aldehydes. 

It has been long appreciated that a chiral environment may differentiate any physical property of enantiomeric molecules. NMR spectroscopy is a sensitive probe for the occurrence of interactions between chiral molecules [4]. NMR spectra of enantiomers in an achiral medium are identical because enantiotopic groups display the same values of NMR parameters. Enantiodifferentiation of the spectral parameters (chemical shifts, spin-spin coupling constants, relaxation rates) requires the use of a chiral medium, such as CyDs, that converts the mixture of enantiomers into a mixture of diastereomeric complexes. Other types of chiral systems used in NMR spectroscopy include chiral lanthanide chemical shift reagents [61, 62] and chiral liquid crystals [63, 64). These approaches can be combined. For example, CyD as a chiral solvating medium was used for chiral recognition in the analysis of residual quadrupolar splittings in an achiral lyotropic liquid crystal [65]. 

A major disadvantage of the tetrahydropyranyl ether as a protecting group is that an asymmetric center is produced at C-2 of the tetrahydropyran ring on reaction with the alcohol. This asymmetry presents no difficulties if the alcohol is achiral, since a racemic mixture results. If the alcohol has an asymmetric center anywhere in the molecule, however, condensation with dihydropyran can afford a mixture of diastereomeric tetrahydropyranyl ethers, which may complicate purification and characterization. One way of surmounting this problem is to use methyl 2-propenyl ether, rather than dihydropyran. No asymmetric center is introduced, and the acetal offers the further advantage of being hydrolyzed under milder conditions than those required for tetrahydropyranyl ethers. Ethyl vinyl ether is also useful as a hydroxyl-... 

When a molecule has two chiral centers that are identically substituted, the number of stereoisomers is reduced from four to three, as is well known for the case of tartaric acid. The three stereoisomers are the d and l forms (enantiomers) and the diastereomeric meso form. The meso form is superimposable on its mirror image, since it has a plane of symmetry and is achiral and optically inactive. The three possible stereoisomers of tartaric acid are shown below ... 

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