High enantiomers

Two recent reports described addition of nitrogen-centered nucleophiles in usefully protected fonn. Jacobsen reported that N-Boc-protected sulfonamides undergo poorly selective (salen) Co-catalyzed addition to racemic epoxides. However, by performing a one-pot, indirect kinetic resolution with water first (HKR, vide infra, Table 7.1) and then sulfonamide, it was possible to obtain highly enantiomer-ically enriched addition products (Scheme 7.39) [71]. These products were transformed into enantioenriched terminal aziridines in straightforward manner. 

In the hydrogenation of 3-substituted itaconate ester derivatives by rhodium-dipamp, the alkoxycarbonyl group at the stereogenic center also exerts a powerful directing effect, comparable to that induced by OH in the kinetic resolution of (a-hydroxyethyl)acrylate, leading to a high enantiomer-discriminating ability up to feR fes = 16 1 (Table 21.18, entry 5) [64]. 

Kinetic resolution results of ketone and imine derivatives are indicated in Table 21.19. In the kinetic resolution of cyclic ketones or keto esters, ruthenium atrop-isomeric diphosphine catalysts 25 induced high enantiomer-discriminating ability, and high enantiopurity is realized at near 50% conversion [116, 117]. In the case of a bicyclic keto ester, the presence of hydrogen chloride in methanol served to raise the enantiomer-discriminating ability of the Ru-binap catalyst (entry 1) [116]. 

As it is well known, enzyme catalyzed reactions can result in high enantiomer selectivity but the use of enzymes is limited by their properties and expressivity. However, enzymes have been utilized in some applications, such as the degradation of /7-chlorophenol [24] beeause of the small amount of enzyme needed under eontinuous flow. 

The catalyst exhibited high enantiomer selectivity in the reaction of the six-membered cyclic acetate roc-lab with KSAc on a 2.5 mmol scale. This led to the isolation of the thioacetate 19aa with 97% ee in 48% yield and the acetate ent-lab with >99% ee in 43% yield (entry 8). The reaction came to a practically complete halt after 51% conversion of the substrate. In order to determine the selectivity factor S, the kinetic resolution of roc-lab was repeated and the ee values of the acetate and thioacetate were monitored over the whole course of the reaction (Fig. 

Aqueous surfactants are another class of catalysts. Substantial rate enhancement is seen in the reaction occurring at the micellar hydrocarbon-water interface, which is ascribed to a concentration of the reactant in the micellar pseudo-phase. Chiral p-nitrophenyl esters derived from phenylalanine are hydrolyzed by a histidine-containing dipeptide at a micellar interphase, at which a very high enantiomer discrimination, kR/ks up to 30.4 at 0°C, is observed (49). As shown in Scheme 20, the enantioselectivity is expressed at the stage at which a transient, zwitter-ionic tetrahedral intermediate leading to the acylimidazole is formed,... 

The P-acetoxy esters 2 were obtained in yields over the range 69-75%, based on the aldehyde and with a high enantiomer excess (ee). In addition, in this case the absence of a base as a co-catalyst is essential in order to avoid retro-aldol reaction of the product. The scope of this methodology is not restricted to aromatic hydroxy acids, as the non-aromatic cyclohexyl analog was also successfidly deracemized (Scheme 13.3). 

So far, enzymatic macrolactonizatiiHis are on a model stage yet. Sih has tested the enantio- and dia-stereo-selectivity in the diolide formation hrom racemic (395). With lipase, high enantiomer selection in favor of the iRJi)-096) has been observed, whereas the diastereoselection is disappointingly low (equation 140). ... 

Phenyl-2-pyridyl-otolylmethyl methacrylate (PPyo-TMA, 27) having a chiral ester group is known to lead to highly enantiomer-selective and helix-sense-selec-tive polymerization by anionic catalysis.84-86 The selection was also found in the radical polymerization of optically active PPyoTMA having various ee s,... 

Chankvetadze, B.,Yamamoto, C., Okamoto, Y. Extremely high enantiomer recognition in HPLC separation of racemic... 

Kuwano R, Sawamm a M, Ito Y (1995) Tetrahedron Asymmetry 6 2521 Robinson A, Li HY, Eeaster J (1996) Tetrahedron Lett 37 8321 for an alternative catalytic method for the reduction of imsaturated carbonyl compoimds in very high enantiomer excess (C0CI2, NaBH4, semicorrin), see Von Matt P, Pfaltz A (1991) Tetrahedron Asymmetry 2 691... 

Table 11.1-21 lists cyclic secondary alcohols that have been synthesized by lipase-catalyzed enantiomer-differentiating acylation (1-129). The compounds that have been obtained by the alternative route of hydrolysis are listed in Table 11.1-16. The complementary nature of the two routes is obvious. For the series of the glycals 9-15, Pseudomonas cepacia lipase-catalyzed acylation works with good to high enantiomer selectivity and yield. myo-Inositol derivatives 17 and 18 may be prepared enantiomer-...

The decarboxylase enzyme shows high enantiomer selectivity reacting only with L-aspartic acid. Thus, L-alanine and D-aspartic acid can be produced from DL-aspartic acid at the same time. 

Reduction of a-keto acetals. Enantioselective reduction by this borohydride (1) in THF at —78°C gives alcohols of (5)-configuration with high enantiomer excess. 

Reaction of the chiral phosphonopropionate 112 with the aldehyde 111 afforded almost exclusively the (R,Z)-diastereomer [70]. The ( )-product was not detected. Although the mechanism and stereochemical course of the reaction is not fully elucidated, it seems likely that the initial step is irreversible under the reaction conditions and hence the (Z)/( ) ratio and the diastereomer ratios result from kinetic control in the initial step. Olefination reagent 112 therefore displays a high enantiomer selectivity for aldehyde 111 [73]. 

An interesting two-step KR in the acetylation oftrons-l,2-cyclohexanediol was realized. First by continuous-flow lipase catalysis in SCCO2, (R, R) -2-acetoxycyclohexane-l-ol [122] was obtained with moderate enantiomer selectivity, while the second acylation step proved to be highly enantiomer selective and gave pure (R,R)-24k. 

Chiral separation is an analytical technique for evaluation of enantiomeric purity of chiral compounds. Such property also found in the optically active polymers. Polyelectrolyte multilayer (PEMU) is an example for such property and made up by polypeptides, such as L-and D-poly(lysine), poly(glutamic acid), poly(iV-(5)-2-methylbutyl-4-vinylpyridininum iodide), poly(styrene sulfonate) etc. PEMUs allow at very high enantiomer permeation rates for chiral membrane separations [139-141]. 

Enantiomer-selective polymerization of J S-(phenoxy-methyl)thiirane with ZnEt2/r-a-amino acid has been reported. The S-enantiomer was consumed preferably and isotactic-rich polymers were obtained. With ZnEt2/t-Leu, a high enantiomer seleaivity (r= 5.36) was observed. 

The first such process is a variant of the oxacyclo-propanation reaction discussed in Section 12-10, as applied specifically to 2-propenyl (allylic) alcohols. However, instead of a peroxycarboxylic acid, the reagent is ferf-butyl hydroperoxide in the presence of titanium (TV) isopropoxide ( Sharpless epoxidation ), the function of the chiral auxiliary being assumed by tartaric acid diethyl ester (Real Life 5-3). The naturally occurring (-l-)-[2/ ,3/ ]-diethyl tartrate and its nonnatural (—)-(25,35) mirror image are both commercial products. One delivers oxygen to one face of the double bond, the other to the opposite face, as shown below, giving either enantiomer of the oxacyclopropane product with high enantiomer excess (Section 5-2). 

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