Quaternary ammonium salts enantiomers

Amines with three different substituents are potentially chiral because of the pseudotetrahedral arrangement of the three groups and the lone-pair electrons. Under normal conditions, however, these enantiomers are not separable because of the rapid inversion at the nitrogen center. As soon as the lone-pair electrons are fixed by the formation of quaternary ammonium salts, tertiary amide N-oxide, or any other fixed bonding, the inversion is prohibited, and consequently the enantiomers of chiral nitrogen compounds can be separated. 

Carnitine is a vitamin-like quaternary ammonium salt, playing an important role in the human energy metabolism by facilitating the transport of long-chained fatty acids across the mitochondrial membranes. An easy, fast, and convenient procedure for the separation of the enantiomers of carnitine and 0-acylcarnitines has been reported on a lab-made teicoplanin-containing CSP [61]. The enantioresolution of carnitine and acetyl carnitine was enhanced when tested on a TAG CSP, prepared in an identical way [45]. Higher a values were reached also in the case of A-40,926 CSP [41]. 

In particular, it is not only the cinchona alkaloids that are suitable chiral sources for asymmetric organocatalysis [6], but also the corresponding ammonium salts. Indeed, the latter are particularly useful for chiral PTCs because (1) both pseudo enantiomers of the starting amines are inexpensive and available commercially (2) various quaternary ammonium salts can be easily prepared by the use of alkyl halides in a single step and (3) the olefin and hydroxyl functions are beneficial for further modification of the catalyst. In this chapter, the details of recent progress on asymmetric phase-transfer catalysis are described, with special focus on cinchona-derived ammonium salts, except for asymmetric alkylation in a-amino acid synthesis. 

Although the enantiomers of chiral amines cannot be separated, such amines can be alkylated to form quaternary ammonium salts where the enantiomers can be separated. Once the lone pair of electrons is locked up in a a bond, pyramidal inversion becomes impossible and the enantiomers can no longer interconvert. 

Of course, any tetrahedral atom, not just caibon, that has four different groups bonded to it is a chirality center, and compounds containing such atoms will exist as a pair of enantiomers. Many such compounds have been prepared and resolved, including the following quaternary ammonium salt and the silicon compound ... 

Quaternary ammonium salts with asymmetric nitrogen atoms. Inversion of configuration is not possible because there is no lone pair to undergo nitrogen inversion. For example, the methyl ethyl isopropyl anilinium salts can be resolved into enantiomers. 

Quaternary ammonium salts of alkaloids have been used for the synthesis of optically active oxiranes from electron-poor olefins under phase-transfer conditions. The enantiomer yield is inversely proportional to the dielectric constant of the solvent,Asymmetric epoxidation in the presence of catalytic amounts of poly-(S)-amino-acids in a triphase system has been described with optical yields up to 96% ... 

The nucleophilic character ofdialkyl sulfides is illustrated by their nucleophilic addition reaction with alkyl halides to form the corresponding sulfonium salts (35) (Scheme 13). Asymmetric sulfonium salts (36) have a tetrahedral configuration therefore, like the analogous chiral saturated carbon compounds, they can be resolved into optical enantiomers (see Chapter 6, p. 81). They are, however, generally less optically stable than sulfoxides, but in sulfonium salts the unshared electron pair can hold its configuration at ordinary temperatures, unlike nitrogen in quaternary ammonium salts, enabling their resolution to be achieved. 

The enantiomers of quaternary ammonium salts such as R RZJWhTX- are isoiabte. 

Historically, the azoniaspiroalkanes have been used to settle two controversial points of stereochemistry. There was much discussion of the valency of nitrogen in quaternary ammonium salts, the two views favouring a tetravalent tetrahedral or a pentavalent pyramidal structure. The dispute was settled by the synthesis of compound (11) by Mills and Warren <25JCS2507> which should be resolvable into enantiomers if the nitrogen has tetrahedral valencies, but not with the pyramidal formula (12) which has a plane of symmetry. The compound was resolved as its (< -a-bromo-camphorsulfonate. 

The same types of surface-imprinted polymers were also used to discriminate between the enantiomers of bifunctional amino acids [24]. In this study, the functional host molecule was the quaternary ammonium salt and the templates were the A -protected amino acids shown in Fig. 5. 

Ammonium salts cannot undergo nitrogen inversion because they do not have an unshared pair. Therefore, those quaternary ammonium salts with four different groups are chiral and can be resolved into separate (relatively stable) enantiomers ... 

Five years later, a similar cinchona alkaloid-derived quaternary ammonium salt was applied for the alkylation of N-(diphenylmethylene) glycine tert-butyl ester by O Donnell et al. [17]. By using either 11b or 12a, both enantiomers of the alkylated products, which could be hydrolyzed to afford the chiral a-amino acids, were obtained in high yield with a maximum of 66% ee. Further optimization indicated that, with the corresponding 9-OH-protected catalyst 11c, the enantioselectivity could be enhanced to 81% ee [6bj. 

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