Chirally selective complexing agent

Higuchi ef al. (1993) initated the exploration of the protein bovine serum albumin (BSA) acting as a chirally selective complexing agent for the amino acid tryptophan in an ultraflltration system. Romero and Zydney (2001) have studied in detail the stereoselective separation of a racemic mixture of D- and L-tryptophan in a solution containing BSA via ultrafiltration. The polyethersulfone UF membrane had a MWCO of 50 000 (sufficient to hold back BSA completely). L-tryptophan preferentially binds with BSA, so less L-tryptophan is present in the filtrate. The observed UF rejection, i of the tryptophan enantiomer i molecule (mol. wt. 240) as such is essentially zero. However, the feed concentration, Ctf of the tryptophan enantiomer i is related to total feed concentration, C y, by... 

In most cases, the stereochemical course of heterocyclic addition can be altered by pre-complexation of nitrones with Lewis acids. In the absence of complexation agents (Et2AlCl, TiCLi), addition of lithio-hetaryl derivatives to chiral 3-alkoxy nitrones (292a-d) gives P-alkoxy-a-hydroxylamino-2-alkylhetaryls (346a-d) in good yields with. vy/i-selectivity. In the presence of diethylaluminum chloride the reaction leads to the same adducts, but with anti-selectivity (Scheme 2.150) (Table 2.12) (581). 

Nonmetallic systems (Chapter 11) are efficient for catalytic reduction and are complementary to the metallic catalytic methods. For example lithium aluminium hydride, sodium borohydride and borane-tetrahydrofuran have been modified with enantiomerically pure ligands161. Among those catalysts, the chirally modified boron complexes have received increased interest. Several ligands, such as amino alcohols[7], phosphino alcohols18 91 and hydroxysulfoximines[10], com-plexed with the borane, have been found to be selective reducing agents. 

Enantioselective fluorination is commonly conducted with chiral agents such as quinine-based [N-F]+ compounds, and these have been successfully utilised in ionic liquids.115,161 Very good yields and selectivities have been obtained in the enantioselective fluorination of /Nkctoesters catalysed by the chiral palladium complex 57, see Scheme 9.2. l l Depending on the substrate employed, substantial acceleration of the reaction rate relative to that in ethanol was observed with yields and selectivities comparable to those obtained in water or ethanol. The reaction rate was found to depend on both the length of the alkyl substituent of the imidazolium cation as, well as on the type of anion present, whereas the selectivity was not affected by such variations. The products were extracted from the ionic liquid phase with diethyl ether, and in that manner catalytic activity was maintained for up to ten cycles. 

Enantiomers of chiral metal complexes have attracted considerable attention as potential structural probes of DNA conformation. Norden and Tjerneld [26] first reported fhe preference of the A enantiomer of lfis(dipyridyl)Fe(II) for the right-handed B-form DNA. The Barton laboratory subsequently developed an elaborate series of chiral metal complexes, some of which were reported to recognize specific DNA conformational features [27-29]. A comprehensive review of the interaction of chiral metal complexes wifh DNA [30] indicated, however, that the structural selectivity of fhese agents is ambiguous in many cases. 

This type of the poljnner may act as an effective complexing agent with cation by the polymer back-bone, and may exert a strong stereoregulation by the isotactic structure of the polymer and by the asymmetric environment produced by chiral amine functions. Preliminary results of the enantiomer selection in the reaction of potassium acetate and a-phenethyl bromide by the optically active isotactic polyepichlorohydrin functionalized by L-2-dimethylamino-3-methylbutylamine gave 5-7% of the stereoselection. Further efforts are needed to achieve high enantioselection. 

The reagent itself may be chiral. Enantiopure forms of l,l -bi-2-naphthol are readily available [35] and can be complexed with lithium aluminum hydride (LAH) to form the selective reducing agent BINAL-H, which reduces a variety of ketones, including the precursor to Pirkle s alcohol, 3.13, a chiral solvating agent mentioned in Section 3.3 (Eq. 3.7) [36]. 

There are very few examples of asymmetric synthesis using optically pure ions as chiral-inducing agents for the control of the configuration at the metal center. Chiral anions for such an apphcation have recently been reviewed by Lacour [19]. For example, the chiral enantiomerically pure Trisphat anion was successfully used for the stereoselective synthesis of tris-diimine-Fe(ll) complex, made configurationally stable because of the presence of a tetradentate bis(l,10-phenanthroline) ligand (Fig. 9) [29]. Excellent diastereoselectivity (>20 1) was demonstrated as a consequence of the preferred homochiral association of the anion and the iron(ll) complex and evidence for a thermodynamic control of the selectivity was obtained. The two diastereoisomers can be efficiently separated by ion-pair chromatography on silica gel plates with excellent yields. 

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