Chirality/Chiral optical methods

Besides chiral optical methods used to differentiate between optical isomers, spectroscopic methods are also an important tool in studying chiral compounds. Especially, magnetic resonance spectroscopy allows differentiation between various isomers of the same optically active chemical compound. NMR spectra of enantiomers as well as spectra of racemic mixtures are identical if measurements are performed in standard NMR solvents. However, shifts of certain proton groups occurring in such compounds can be discerned if these compounds are transformed into diastereoisomers [14]. Classic methods used to accomplish this goal involve ... 

Our approach for chiral resolution is quite systematic. Instead of randomly screening different chiral acids with racemic 7, optically pure N-pMB 19 was prepared from 2, provided to us from Medicinal Chemistry. With 19, several salts with both enantiomers of chiral acids were prepared for evaluation of their crystallinity and solubility in various solvent systems. This is a more systematic way to discover an efficient classical resolution. First, a (+)-camphorsulfonic acid salt of 19 crystallized from EtOAc. One month later, a diastereomeric (-)-camphorsulfonic acid salt of 19 also crystallized. After several investigations on the two diastereomeric crystalline salts, it was determined that racemic 7 could be resolved nicely with (+)-camphorsulfonic acid from n-BuOAc kinetically. In practice, by heating racemic 7 with 1.3equiv (+)-camphorsulfonic acid in n-BuOAc under reflux for 30 min then slowly cooling to room temperature, a cmde diastereomeric mixture of the salt (59% ee) was obtained as a first crop. The first crop was recrystallized from n-BuOAc providing 95% ee salt 20 in 43% isolated yield. (The optical purity was further improved to -100% ee by additional recrystallization from n-BuOAc and the overall crystallization yield was 41%). This chiral resolution method was more efficient and economical than the original bis-camphanyl amide method. 

Chiral chemical shift reagents for NMR analysis are also useful, and so are optical methods. 

This unit describes those methods that can differentiate between enantiomers found in foods that contribute to their taste and aroma. These compounds are volatile odorants that are most easily analyzed using enantioselective high resolution-gas chromatography (HRGC). Other methods exist for the separation and analysis of chiral compounds, which include optical methods, liquid and planar chromatography, and electrophoresis, but for food volatiles, gas chromatography has evolved to the point where it is now the cornerstone for the most comprehensive analysis of volatile compounds. 

Both techniques can be applied in two ways. In the first method the enantiomeric mixture (or racemate) is converted into a diastereoisomeric mixture with a suitable optically pure reagent, and this mixture chromatographed on a column having an achiral stationary phase. Separation then depends on the differential molecular interactions of the diastereoisomers with the stationary phase. In the second method, the stationary phase on the support material (usually chemically bonded) contains a chiral, optically pure residue. In this case the mixture of enantiomers which is loaded directly on to the column is separated by virtue of differential diastereoisomeric molecular interactions between each enantiomer and the optically pure stationary phase. 

In this chapter two different kinds of phase materials are presented the first is a chiral diamide selector bonded to a polysiloxane matrix the other selector system is a calix[4]arene with chiral residues which is attached to a polysiloxane backbone (Sect. 2.4). These systems were used in direct optical methods based on a change in the refractive index or the optical thickness of a transparent polymeric layer. 

The analysis of chiral compounds to determine their optical purity is still not a trivial task. The analysis method has to differentiate between the two antipodes and, thus, has to involve a chiral agent. However, the development of chiral chromatography, especially HPLC (high-performance liquid chromatography), has done a significant amount to relieve this problem. The purpose of this book is to discuss large-scale synthetic reactions, but the reader is reminded that the development of chiral analytic methods may not have been a trivial undertaking in many examples. 

The one-handed helicity of 28 induced by a small amount of chiral (R)-39 and subsequently amplified by an achiral amine 40 (Fig. 16) can also be memorized in the same way by the replacement of (R)-39 and 40 with achiral amines [87]. The chiral amplification combined with the macromolecular helicity memory will offer a highly sensitive, chirality sensing method for chiral molecules even when their optical activities are too small to detect by conventional spectroscopic means. 

Chiral chromatography methods are considered by many to be superior to conventional methods in that, besides analytical applications, they offer the greatest potential for the preparation of optically pure forms of the isomers [5,27,28]. In these examples the third chiral species is an integral part of the LC (or GC) system and may appear as a plain stationary phase (cyclodextrins),... 

In order to provide the asymmetric environment lacking in zeolites during the reaction a chiral source had to be employed. For this purpose, in the approach known as the chiral inductor method (CIM), where optically pure chiral inductors such as ephedrine were used, the nonchiral surface of the zeolite becomes locally chiral in the presence of a chiral inductor [186-188]. This simple method affords easy isolation of the product as the chiral inductor and the reactant is not connected through either a covalent or an ionic bond. 

The optically active form of 1-phenyl-1-pentanol has been prepared by a variety of methods.4,5 The present procedure is a modification and extended description of our previously published2 chiral solvent method. DDB and other auxiliary agents from tartaric acid lead to a wide range of optically active products from achiral components with prochiral centers (enantioselective syntheses). A list of examples of DDB applications is found in the accompanying procedure describing its preparation from tartaric acid. 

In principle, any of the photoproducts shown in Table 4 could have been prepared in enantiomerically pure form by irradiating their achiral precursors in solution to form a racemate and then separating the enantiomers by means of the classical Pasteur resolution procedure [36]. This sequence is shown in the lower half of Fig. 3. The top half of Fig. 3 depicts the steps involved in the solid-state ionic chiral auxiliary method of asymmetric synthesis. The difference between this approach and the Pasteur method is one of timing. In the ionic chiral auxiliary method, salt formation between the achiral reactant and an optically pure amine precedes the photochemical step, whereas in the Pasteur procedure, the photochemical step comes first and is followed by treatment of the racemate with an optically pure amine to form a pair of diastereomeric salts. The two methods are similar in that the crystalline state is crucial to their success. The Pasteur resolution procedure relies on fractional crystallization for the separation of the diastereomeric salts, and the ionic chiral auxiliary approach only gives good ees when the photochemistry is carried out in the crystalline state. 

A very utilitarian sequence was developed by Sharpless, using his chiral epoxidation method, to prepare epoxy alcohol 40. Scheme 2.15 depicts the sequence, starting with the inexpensive diene alcohol 38. As pointed out by Sharpless, the original procedure gave poor yields of relatively water-soluble epoxides such as 40, but a modified work-up procedure largely circumvents this difficulty, allowing for direct oxidation of 41 in excellent optical purity. 

The enantioselective addition of HX to a./i-unsaturated carbonyl compounds under catalysis by optically active bases is known in great detail for systems in which the stereogenic center is created on the ketone skeleton through the connection of X (method ) or on chiral HX1 (method ) by deracemization 167,168. 

---