Complexes chirally resolved

A related receptor based upon a chiral, resolved Zn(ll) porphyrin complex has been shown to differentiate between enantiomers of a range of substituted amino acids with selectivity of up to 96% for L-benzyloxycarbonylvalinate. The combination of metal coordination and hydrogen-bonding interactions are again responsible for the observed selectivity." ... 

Both the ally lie alcohol and tert-hutyX hydroperoxide are achiral, but the product epoxide is formed in high optical purity. This is possible because the catalyst, titanium tetraiso-propoxide, forms a chiral (possibly dimeric [36]) complex with resolved diethyl tartrate [(+)-DET] which binds the two achiral reagents together in the reactive complex. The two enantiotopic faces of the allylic double bond become diastereotopic in the chiral complex and react at different rates with the tert-butyl hydroperoxide. Many other examples may be found in recent reviews [31, 37-39]. 

To prepare the enantiomerically pure iron acyl complex (R)-(39), a precursor diastereomeric menthoxyaUcyl complex was resolved and then manipulated (Scheme 14). More recently resolution of the chiral-at-metal acyl complexes themselves was achieved, and this has become the basis for a commercial preparation of the iron acyl developed for use as a chiral auxiliary (see below). Cationic iron complex (43) was treated with potassium L-mentholate to produce diastereomeric esters (44) that were not isolated but were reacted with LiBr/MeLi (Scheme 15). After chromatography and recrystallization the enantiomerically pure ironacyl complex (5 )-(39a) was obtained. It was suggested that only one diastereomeric ester can react (with inversion of configuration at iron, as shown) with the methyl nucleophile the unreactive diastereomer suffers from severe steric congestion about the electrophilic CO ligand. 

Simple chiral phosphines have already been mentioned (Section 3.1.3) and the macrocycle enantiomers are discussed below (Section 4.6). Current research in this area is concentrated on bidentate chiral phosphines, such as the ligands (24)-(27). Although their transition metal complexes are normally used for stereospecific synthesis, Whitmire and coworkers used the molybdenum complexes to resolve their racemic bisphosphines via flash chromatography. The phosphines were decomplexed by reductive cleavage at low temperatures (-78 °C) using sodium naphthalenide (Scheme 1). 

The use of chiral mobile phases has both advantages and disadvantages. For example, the multiple equilibria occurring in the mobile phase and in the stationary phase complicates elucidation of the separation mechanism. The presence of the chiral mobile phase additive can also complicate detection. For instance, additives with relatively high UV absorbance decrease the detection limit of the separated enantiomers when using UV detection. Furthermore, resolved enantiomers enter in the detector cell in the form of complexes with the chiral resolving ligand. These complexes are diastereomers and therefore may differ in molecular absorptivity, as well as other properties. As a consequence, it is necessary to have a separate calibration curve for each enantiomer. 

Separation of chiral isomers requires chiral counterions. Cations are frequently resolved by using the anions z -tartrate, antimony d-tartrate, and a-bromocamphor-iT -sulfonate anionic complexes are resolved by the bases brucine or strychnine or by using resolved cationic complexes such as [Rh(en)3] " . In the case of compounds that racemize at appreciable rates, adding a chiral counterion may shift the equilibrium even if it does not precipitate one form. Apparently, interactions between the ions in solution are sufficient to stabilize one form over the other. 

A chiral resolving agent is a chiral mobile-phase additive or a chiral stationary phase that preferentially complexes one of the enantiomers. 

Chiral stationary phases have received the most attention. Here, a chiral agent is immobilized on the surface of a solid support. Several different modes of interaction can occur between the chiral resolving agent and the solute." In one type, the interactions are due to attractive forces such as those between ir bonds, hydrogen bonds, or dipoles. In another type, the solute can fit into chiral cavities in the stationary phase to form inclusion complexes. No matter what the mode, the ability to separate these very closely related compounds is of extreme importance in many fields. Figure 32-16 shows the separation of a racemic mixture of an ester on a chiral stationary phase. Note the excellent resolution of the R and S enantiomers. 

In addition, Durand et al. have recently used an axially chiral monodentate phosphine, such as (I j-Ph-BINEPINE (Scheme 2.62), as a chiral resolving agent of a racemic palladium complex prepared from a 2-ferrocenyl-l,10-phenanthroline ligand. The reaction evolved through a DKR process, leading after recrystallisation to the isolation of only one of the two possible diastereoisomers. 

Chromium(VI) can produce a green complex, with blue iridescence (chirally resolvable by organic and organo-metaUic cations) ... 

The green product, stable when dry, is moderately stable in solution with excess HC03", although the chirally resolved form racemizes quickly. This complex, with various amounts of CN", NH3 (and NH4 ) and NO2", and often with catiytic charcoal and heat, can be converted conveniently to numerous corresponding mixed complexes, e.g., [mer-Co(CN)3(NH3)3], slightly soluble and yellow. The carbonate ions are especially safely displaced by otherwise easily oxidized ligands. 

It was found that the mobile phase composition showed an important role to improve the enantioseparations and all of the enantiomers could be baseline resolved imder the optimized experimental conditions. Three pairs of enantiomers, which could not be separated with only di-n-butyl-/-tartrate, obtained good chiral separations using the complex chiral selector. 

The resolutions described above are based on the formation of diaste-reomeric complexes with a column stationary phase or an enzyme. The more common alternative is to bond the enantiomers covalently to a chiral resolving agent to make stable diastereomeric molecules, separate those diastereomers by chromatography or recrystallization, and then disassemble each purified diastereomer to obtain the resolved enantiomers. 

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