Phase tartaric acid derivatives

The enantioselectivity a is defined as the distribution ratio of one single enantiomer over the two chiral phases and has been determined experimentally for a variety of compounds (Table 5-1). It has been known from work by Prelog [66, 67] that tartaric acid derivatives show selectivities towards a-hydroxyamines and amino acids. However, from Table 5-1 it is obvious that tartaric acid derivatives show selectivity for many other compounds, including various amino bases (e.g. mirtazapine (10)) and acids (e.g. ibuprofen (11)). The use of other chiral selectors (e.g. PLA)... 

The asymmetric addition of glycine enolates to acrylates was also achieved by use of the tartaric acid-derived phase-transfer catalysts 27 and 28 (Scheme 4.9). Arai, Nishida and Tsuji [13] showed that the C2-symmetric ammonium cations 27a,b afford up to 77% ee when t-butyl acrylate is used as acceptor. The cations 28 are the most effective/selective PTC identified by broad variation of the substituents present on both the acetal moiety and nitrogen atoms [14], In this study by Shibasaki et al. enantiomeric excesses up to 82% were achieved by use of the catalyst 28a (Scheme 4.9) [14], Scheme 4.9 also shows the structure of the guanidine 29 prepared by Ma and Cheng in the absence of additional base this also catalyzes the Michael addition of the glycine derivative 22 to ethyl acrylate, albeit with modest ee of 30% [15],... 

Utilization of the single hydrogen bond between pyridine and benzoic acids in SLCP s has been a source of inspiration for other groups in the development of main-chain supramolecular polymers based on diacids and dipyridines.53-56 Supramolecular rod-coil polymers have been developed by assembly of 4,4 -bipyridines and telechelic polypropylene oxide with benzoic acid end-groups, which show highly ordered liquid crystalline phases.57 The use of tartaric acid derivatives in combination with bipyridine units resulted in the formation of hydrogen-bonded, chiral main-chain LCP s, as has been shown by circular dichroism measurements, optical microscopy, and X-ray data.58,59... 

Since enantiomer separation requires the Intervention of some chiral agent, one may utilize either chiral mobile phase additives (CMPA) or chiral stationary phases (CSPs). While the requirement that one add a chiral substance to the mobile phase has obvious limitations for preparative separations, it is not a serious problem for analytical separations. Indeed, for some types of compounds (e.g. amino acids) this approach may be preferred. Quite an extensive literature exists for the use of mobile phases containing chiral bidentate ligands and copper ions for the "ligand exchange" resolution of underlvatized amino acids (1, 2) and for N-dansyl derivatives of amino acids Tartaric acid derivatives have also been used as CMPAs (5). 

Waser M, Gratzer K, Herchl R, Miiller N (2012) Design, Synthesis, and Application of Tartaric Acid Derived N-Spiro Quaternary Ammoniiun Salts as Chiral Phase-Transfer Catalysts. Org Biomol Chem 10 251... 

With respect to the application of tartaric acid-derived PTCs [22,23] for natural product synthesis, the work of Shibasaki s group should be highlighted herein. Using his powerful bidentate TaDiAS PTCs, asymmetric phase-transfer-catalyzed alkylations, Michael addition reactions, and Mannich-type reactions have been systematically carried out. 

Figure 12.11 Tartaric acid-derived quaternary ammonium salt phase-transfer catalysts.

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

Figure 1.14. Schematic plan view of the outermost layer of Cu(l 10) showing the proposed adsorption structures for the ordered bitartrate phases, (]°) and ( ) derived from (R,R) and (W,.V)-forms of tartaric acid, respectively. The molecular adsorbates are represented by shaped ellipses.

Isoflavone derivatives along with nonvolatile components in soy sauce were also analyzed by gradient reversed-phase HPLC. This HPLC profile of soy sauce was further utilized by a pattern recognition program to understand the quality differences of soy sauces (132), and three isoflavone derivatives (esters of tartaric acid with daidzein, genistein, and 8-hydroxygenistein) were found to contribute significantly to the differentiation in fermented soy sauce. Fermented... 

Numerous examples of stereospecific reactions in the gas phase are reported in the mass spectrometric literature [1,2]. Many if not most of them, however, deal with relatively rigid systems, e.g., 1, or polyfunctional molecules such as derivatives of tartaric acid [6] the latter gave rise to the first chirality effect observed in mass spectrometry [7]. For stereogenic centers linked by flexible alkyl chains, however, diastereoisomeric differentiation in ion fragmentation is often poor. Two epimers of the aminoalkanol 2, for example, show quite small differences in their mass spectra whereas these differences increase if the two centers are linked by cyclization upon formation of 3 as indicated in Scheme 2 with the epimeric center being marked by an asterisk [8]. 

Gas-Phase Conformational Analysis of (R,R)-Tartaric Acid and Its Derivatives... 

Unlike the acid, its amides that have been so far examined theoretically appear to favour the G-t- (i.e. gauche+) conformation of the carbon chain with 6-membered ring type of hydrogen bonding, namely C=O...HO(P) (cf Fig. 3). The G+ conformation in the gas phase, on the semiempirical level, has also been found favoured in a non-symmetric derivative methyl ester of tartaric acid monoamide (In Fig. 1 X=NH2, Y=OCH3). This type of conformation has been observed experimentally only in TMDA via NMR in a non-polar solvent. (Gawrohski et al.,... 

The well known Wittig reaction has been reported to occur in solid phase. In this procedure a 1 1 mixture of the finely powdered inclusion compound of cyclohexanone or 4-methyl cyclohexanone and (-)-B (derived from tartaric acid s and a catalytic amount of benzyltrimethyl ammonium hydroxide) was heated at 70 °C with Wittig reagent carbethoxymethylene triphenylphosphorane to give optically active 1-(carbethoxymethylene) cyclohexane (Scheme 17) or... 

Liquid-crystalline polymeric supramolecu-lar species 23 has been prepared by the association of bifunctional H-bonding components [41, 42]. These bifunctional individual components were derived from l(+), d(-), and meso (M) tartaric acids, respectively. It is interesting that the liquid-crystalline phases of the polymeric complexes consisting of chiral species are more stable than those of polymers consisting of meso components. The complex based on l-(+)-tartaric acids shows a mesophase from room temperature to 254 °C, while the mesophase... 

Shibasaki developed a library of more than 40 chiral phase-transfer catalysts readily derived from tartaric acid [75]. Catalyst 91 proved optimal and provides access to -amino acids in high optical purities (Scheme 10.14) [75]. For example, alkylation of 78 with bromide 90 in the presence of 91 provided 92 in 80% yield and 88% ee this compound was subsequently employed in the synthesis of the serine protease inhibitor aeruginosin 298-A (93) [76]. 

Alkaloids, for example, quinine, are widely applied as catalytic reagents in chiral organic syntheses and also in the production of HPLC stationary phases for chiral separations. Cinchona alkaloids also induce the enantioselection of chiral fluoro-compounds analyzed by FNMR spectroscopy [32]. (-)-Brucine and (-)-berberine mixed with silica gel were used for preparation of thin-layer plates to resolve racemic amino acids. Other optically active pure enantiomers of natural compounds are applied for impregnation of TLC plates (-l-)-tartaric acid, L-aspartic acid [33]. (—)-Menthol is used for preparation of diastereomeric derivatives in indirect enantiomeric separation of, for example, 2- and 3-hydroxy acids [34]. 

---