Enantioselective discrimination

It is also clear that entrapment of such complexes in zeolitic cages will most likely affect the enantioselective discrimination power. Since molecular modelling predicted that the actual Jacobsen catalyst (24) would not fit into a supercage, an unsubstituted ligand was ligated to zeolite Mn ions (25).[142] Methylstyrene could be epoxidized with an epoxide yield of 4% and an ee of 58%. In analogous homogeneous conditions, a yield of 28% and an ee of 60% were achieved,... 

The stereoselective behaviour of heterogeneous Ziegler-Natta catalysts is caused by the chirality of the catalytic active site but not by chiral atoms in the growing chain. The model devised by Corradini et al. [282] can explain the experimental results relative to the first insertion of a chiral a-olefin into an initial Ti-CH3 bond [377,378], i.e. the absence of enantioselectivity (discrimination between re and si insertions) but the presence of diastereoselectivity... 

Weingarten et al. [372] combined parallel (split) synthesis of SO libraries and parallel (visual) screening to find the SO with the most enantioselective discrimination ability. Thus, a60(15x2x2) member SO library with the general structure as presented in Fig. 9.28 (constructed of module A which consisted of 15 different (K)- and... 

Finally, the bacterial PTE mentioned above has also been exhaustively studied with regard to its enantioselectivity. Initial studies used the known crystal structure of PTE to identify the substrate-binding pocket. This was then rationally evolved for enhancement and relaxation of the stereospecificity.97 Most recently, a combinatorial library has been screened for the resolution of chiral phosphate, phosphonate, and phosphinate esters.124 This work identified two variants with markedly different preferences for 5p- and Rp-enantiomers of 4-acetylphenyl methyl phenyl phosphate. One variant preferentially catalyzed hydrolysis of the 5p-enantiomer by a factor of 3.7 x 105, while the other preferentially catalyzed hydrolysis of the A p-enantiomer by a factor of 9.7 x 102 - an enantioselective discrimination of 3.6 x 108. 

The enantioselective discrimination of one of the hydroxyl groups of meso-diols can give chiral monoprotected diols, which serve as versatile intermediates for asymmetric organic synthesis. In addition to the enzymatic methods, a number of chemical approaches have been reported using chiral 1,2-diamine catalysts, chiral phospholane-based catalysts, planar chiral DMAP derivatives, and oligopeptide-based catalysts [2,28], Surprisingly, however, relatively a few publications are devoted to this reaction with cinchona-based organocatalysts. 

Attempts have been made to determine enantiospecific differences between enantiomers and racemates in solution using microcalorimetry [29]. The microcalorimetric method can be used to understand the magnitude of stereoselective interactions that could result from the mixing of solutions of enantiomers of a chiral excipient. The heat evolved or heat of solution (A/T ° ) is measured for the racemate as well as the enantiomers and could be indicative of enantioselective discrimination. However, Horeau and Guette [30] reported that enantioselective interaction in an aqueous medium measured using microcalorimetry may be inconsistent and flawed because of the insufficient purity of the optically active samples used and the insensitivity of the measurement relative to small differences in magnitude of the observed effects. 

Yamamoto and Maruoka have reported the first aluminum-promoted asymmetric Claisen rearrangement [5]. They used a chiral 3,3 -bis(triarylsilyl)-substi-tuted binaphthol (BINOL) aluminum reagent 1 to promote the enantioselective coordination to one of the two enantiomeric oxygen lone pairs of 2. Enantioselective discrimination is based on two chair-hke transition states A and B to give two enantiomeric products 3, respectively (Scheme 2.2). 

While the first instance of MS-based enantioselective discrimination was demonstrated by CI-MS, more recent work has focused on the use of fast atom bombardment (FAB), matrix-assisted laser desorption/ ionization (MALDI), and electrospray ionization (ESI) sources. All of these sources are considered to be soft-ionization sources due to the low internal energy they impart on a molecule as it is converted to a gas phase ion. The result is a lack of fragmentation, but in cases where source parameters are properly tuned, noncova-lent complexes can also be preserved from the condensed phase and transferred into the gas phase. 

Of the two related techniques, FAB found far greater use in studies of enantioselective discrimination as compared to other desorption/ionization methods, such as MALDI and secondary ion mass spectrometry (SIMS). Chan and coworkers demonstrated enantiodiscrimina-tion of amino acids by a-, P-, and y-cyclodextrins using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) [28]. The observed levels of enantioselectivity were found to be dependent on the size of cyclodextrin cavities, as well as on the length and functionality of the amino acid side chain. Vairamani and coworkers demonstrated discrimination of amino acid methyl esters using various monosaccharide hosts by liquid secondary ion mass spectrometry (LSIMS) [29]. It is curious that more work has not been done using these sources. MALDI, in particular, is a simple and straightforward technique. Various researchers have demonstrated the observation of noncovalent complexes [30-32], for example, between peptides and proteins, but relatively little work has been performed that focuses on studying enantioselective noncovalent interactions by MALDI-MS. 

FIGURE 9.2 General schematic for studying enantioselective discrimination using the KM. A metal (M) is mixed in solution with a chiral reference compound (CR) and an analyte of interest (A ). A ternary complex is isolated in the gas phase and induced to fragment. The logarithm of the ratio of product ion channels is measured and can be correlated with the enantiomeric purity of A. ... 

An IRIS 1.0, within experimental error, indicates enantioselective discrimination. The designation of an IRIS value is also convenient for reporting the configurational preference of binding without having to indicate it specifically, together with the value (as we have... 

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