Chirality enhanced

Essentially, the origin of spontaneous chiral resolution is the same as the previous example. When molecules with the same chiral conformation form small chiral domains due to packing entropy effects, the same chiral conformation of molecules is stabilized when they approach the chiral domain. Thus both chiral domains with different chiral conformations grow, resulting in spontaneous chiral resolution [6-8]. Chirality enhancement occurs even in such chiral domains. For instance, chirality in both segregated chiral domains is enhanced by doping nonchiral bent-shaped molecules (BSMs) with nonchiral rod-shaped molecules (RSMs), as observed by circular dichroism (CD) or optical rotatory power (ORP) [9],... 

In this chapter very unusual phenomena are described, i.e., (1) chirality enhanced by achiral or nonchiral molecules, (2) spontaneous chiral resolution in apparently nonchiral molecular systems composed of rod-, bent-, or disk-shaped... 

Finally, the difference of chirality enhancement in the N and SmC phases should be mentioned. As shown in Sect. 2.1, enhancement rate in SmC is about one order of magnitude larger than that in N. In the SmC chirality enhancement is attributed to two effects (1) the interaction between bent-core and chiral host molecules and (2) the coupling between ee, tilt, and spontaneous polarization. The latter effect is absent in the N phase and is an additional effect in SmC. Moreover, the chiral discrimination parameter AU is expected to be larger in SmC than in N because of a confined geometry, i.e., smectic layer. 

Since there have been no previous studies of spin-polarized electron induced reaction asymmetries in adsorbed chiral molecules, the exact manner by which the enhancement occurs is unclear. If the orbital occupied during DEA is sufficiently diffuse so as to sample the regions of the molecule responsible for the chiral structure [92] then enantiomeric specific dissociation will result. On the other hand, it has been theorized that two enantiomers will be ionized at different rates by longitudinally spin-polarized electrons [126]. If there are sufficient numbers of higher energy spin-polarized secondary electrons and the final state reached following ionization is dissociative, then this could lead to chiral enhancement. 

Kommuru, T. Khan, M.A. Reddy, I.K. Effect of chiral enhancers on the permeability of optically active and racemic metoprolol across hairless mouse skin. Chirality 1999, 11, 536-540. 

Table 3 The Permeability Parameters of Pure S-Isomer and R-(from Racemic) Timolol Maleate (TM) Across Hairless Mouse Skin with and Without Chiral Enhancers... 

Figure 10 Permeation profiles of R-enantiomer of timolol maleate (R-TM) in the presence and the absence of selected chiral enhancers. ( ) R-enantiomer, ( ) R-enantiomer-I-0.2% w/v D-limonene, (A) R-enantiomer-I-0.2% w/v L-menthol, and (O) R-enantiomer-I-0.2% w/v carvacrol. (Adapted from Refs. 39 and 81.)...

Fig. 4. The synthesis of a chirally enhanced liquid-crystal solvent.

In addition to the studies mentioned above, chiral alcohols have been used as H-bonding catalysts in a vinylogous aldol reaction of Chan s diene with aldehydes [73], in an enantioselective Strecker reaction [74], and in the enantioselective addition of aza-enamines to imines [75]. Taddol has also found use as a memory of chirality enhancer in the stereoselective synthesis of (i-lactams from amino acid derivatives [76, 77]. 

Bonache MA, Lopez P, Martin-Martmez M, Garci a-Lopez MT, Cativiela C, Gonzalez-Muniz R. Steroselective synthesis of amino acid-derived 3-lactams. Experimental evidence for TADDOL as a memory of chirality enhancer. Tetrahedron 2006 62(1) 13(U138. 

Park and coworkers proposed that mesoporous silica having L-proline could enhance the chiral enhancement in asymmetric catalysis. The use of r-proline as active site would be useful for the asymmetric diethyl malonate addition reaction and asymmetric epoxidation reaction of a,p-unsaturated aldehydes. In addition, the plugged mesoporous sihca as a support certainly allowed the formation of dual mesoporosities. In particular, they can provide confinement effect for better enantiomeric excess in the asymmetric catalysis [63]. 

Mesoporous silica functionalized by chiral primary-tertiary diamine/Bronsted acid conjugates was successfully synthesized by Xiaobing et al. Two functionalities of this material, that is, the chiral organofunctional group and the mesoporous support, provided the chiral enhancement in the asymmetric aldol reaction of acetone with various aldehydes. The catalyst exhibited good activity and enantioselectivity without loss of activity. Particularly, the catalytic activity of SBA-15 with an immobilized chiral organic group increased in enantiomeric excess value of the reaction product as compared with silica gel as the support [89]. 

Most importantly, enantioselectivity benefits considerably from the use of water. This effect could be a result of water exerting a favourable influence on the cisoid - transoid equilibrium. Unfortunately, little is known of the factors that affect this equilibrium. Alternatively, and more likely, water enhances the efficiency of the arene - arene interactions. There is support for this observation"" . Since arene-arene interactions are held responsible for the enantioselectivify in many reactions involving chiral catalysts, we suggest that the enhancement of enantioselectivity by water might well be a general phenomenon. 

A study was conducted to measure the concentration of D-fenfluramine HCl (desired product) and L-fenfluramine HCl (enantiomeric impurity) in the final pharmaceutical product, in the possible presence of its isomeric variants (57). Sensitivity, stabiUty, and specificity were enhanced by derivatizing the analyte with 3,5-dinitrophenylisocyanate using a Pirkle chiral recognition approach. Analysis of the caUbration curve data and quaUty assurance samples showed an overall assay precision of 1.78 and 2.52%, for D-fenfluramine HCl and L-fenfluramine, with an overall intra-assay precision of 4.75 and 3.67%, respectively. The minimum quantitation limit was 50 ng/mL, having a minimum signal-to-noise ratio of 10, with relative standard deviations of 2.39 and 3.62% for D-fenfluramine and L-fenfluramine. 

Chiral Controller. (Synonymous with Chiral Auxiliary). A chiral structural unit which when attached to a substrate enhances stereoselectivity in the formation of new stereocenter(s). 

The structural variations reported by Cram and coworkers relate to an appreciable extent to the various ancillary functions which have been appended to the binaphthyl units or elsewhere in the macrocyclic system. Enhancements of the chiral barrier or functionalization through arms has generally been effected at the 3-or 6-positions. These positions are adjacent to the hydroxyl group or directly across the second ring from it, respectively. 

Evans et al. reported that the bis(imine)-copper (II) complex 25, prepared from chiral bis(imine) ligand and Cu(OTf)2, is also an effective chiral Lewis acid catalyst [34] (Scheme 1.44, Table 1.18). By tuning the aryl imine moiety, the bis(2,6-dichlor-ophenylimine) derivative was found to be suitable. Although the endojexo selectivity for 3-alkenoyloxazolidinones is low, significant improvement is achieved with the thiazolidine-2-thione analogs, for which both dienophile reactivity and endojexo selectivity are enhanced. 

Corey et al. synthesized a chiral bis(oxazoline)Fe(III) catalyst 30, the ligand of which was prepared from chiral phenylglycine. The catalyst was formed by the reaction of the ligand with Fel3 in the presence of I2.12 greatly enhances the Lewis acidity of the catalyst owing to the formation of a cationic species [39] (Scheme 1.49). 

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