Chiral molecules determinations

Each act of proton abstraction from the a carbon converts a chiral molecule to an achi ral enol or enolate ion The sp hybridized carbon that is the chirality center m the start mg ketone becomes sp hybridized m the enol or enolate Careful kinetic studies have established that the rate of loss of optical activity of sec butyl phenyl ketone is equal to Its rate of hydrogen-deuterium exchange its rate of brommation and its rate of lodma tion In each case the rate determining step is conversion of the starting ketone to the enol or enolate anion... 

Techniques for determining the absolute configuration of chiral molecules were not developed until the 1950s and so it was not possible for Eischer and his contemporaries to relate the sign of rotation of any substance to its absolute configuration A system evolved based on the arbitrary assumption later shown to be correct that the enantiomers... 

The property of chirality is determined by overall molecular topology, and there are many molecules that are chiral even though they do not possess an asymmetrically substituted atom. The examples in Scheme 2.2 include allenes (entries 1 and 2) and spiranes (entries 7 and 8). Entries 3 and 4 are examples of separable chiral atropisomers in which the barrier to rotation results from steric restriction of rotation of the bond between the aiyl rings. The chirality of -cyclooctene and Z, -cyclooctadiene is also dependent on restricted rotation. Manipulation of a molecular model will illustrate that each of these molecules can be converted into its enantiomer by a rotational process by which the ring is turned inside-out. ... 

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. 

Figure 1.1 Schematic diagram explaining the Cahn-Ingold-Prelog convention for determining the absolute stereochemistry of a chiral molecule.

This chapter has provided a general introduction to stereochemistry, the nomenclature for chiral systems, the determination of enantiomer composition and the determination of absolute configuration. As the focus of this volume is asymmetric synthesis, the coming chapters provide details of the asymmetric syntheses of different chiral molecules. 

The dissimilar association of enantiomers with another chiral molecule (Figure 4.18) also allows their determination if the molecule is part of a chromatographic system. The unequal interactions result in different rates of migration of the enantiomers through the column. The chiral molecule may be a component of the mobile phase or the stationary phase of the system. Typical examples of the separation of... 

In this study, an important piece of information was gleaned regarding the mechanism of the reaction from the assignment of the absolute sign of the polar axis. Of course, in transformations of this type, if the reaction mechanisms are well established, one may proceed in a reverse manner and assign the absolute polarity of the crystal (and therefore the absolute configuration of the chiral molecules) by determining the preferential direction of the attack. 

In terms of die original discussion of Section II, what one needs to know is the orientation of die chiral molecule in a chiral crystal relative to die crystal axes. The absolute orientation of the molecule or of a sequence of molecules in the crystal can be determined by high-resolution electron microscopy, especially in cases like rubidium tartrate or other organometallics in which die problem is to determine the relative position of die heavy metal km with respect to die... 

The new terms, which ought to be used for characterization of steric elements only and not of compounds, permit several generalizations. Any chiral molecule for which all elements of stereoisomerism have been determined must contain at least one that is pherochiral. A compound must be chiral if the total number... 

At the beginning of this paragraph, it has been mentioned the application of the kinetic method to characterize chiral ions. If A is an unknown chiral molecule and ref is a reference molecule of defined configuration, the stability difference between their homochiral and heterochiral complexes with I, [A -Lref] and [A -Lref], can be determined by the dissociation of the corresponding [A -L(ref)2] and [A -L(ref)2] clusters (Scheme 4). 

Several CD derivatives (charged and uncharged) are available which should allow the separation of most chiral molecules with at least one of them. However, due to the complexity of chiral recognition mechanisms, the determination of the best selector based on the analyte structure is challenging. Eurthermore, separations using CDs are influenced by numerous factors, so that no general rule can be applied for the successful resolution of enantiomers. ... 

Richardson s synthesis of ( )-pentenomycin I displayed similar levels of conceptual elegance and was also very well received. In the mid-1970s, synthetic organic chemistry was far less refined that it is currently, and the synthesis of such chiral molecules as (—)-pentenomycin looked extremely formidable. However, Richardson was never put off by the degree of difficulty of any problem he faced he was always determined to overcome that problem. His account of the (—)-pentenomycin I synthesis reveals the many traps and snares in which he was successively caught during that synthetic endeavor, before the successful synthesis shown in Scheme 36 was eventually accomplished. 

Stereoselective catalysis using biocatalysts (e.g. enzymes) and also of rationally designed small chiral molecules, deals essentially with the same principle the spatial and selective docking of guest molecules to a chiral host molecule to form complementary interactions to form reversible transient molecule associates (see the specific sections in this volume). The enantiomeric excess of a certain reaction and hence the result will be determined by the degree of chiral discrimination. Along the same theoretical lines the concepts of protein (enzyme, antibody, etc.) mimicks via imprinted" synthetic polymers should be mentioned and will be discussed further. 

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