Enantiomeric excesses from

Likewise, the influence of the ligand catalyst ratio has been investigated. Increase of this ratio up to 1.75 1 resulted in a slight improvement of the enantioselectivity of the copper(L-tryptophan)-catalysed Diels-Alder reaction. Interestingly, reducing the ligand catalyst ratio from 1 1 to 0.5 1 resulted in a drop of the enantiomeric excess from 25 to 18 % instead of the expected 12.5 %. Hence, as anticipated, ligand accelerated catalysis is operative. 

Table 1 Photoproduct yields and enantiomeric excesses from irradiation of crystalline complexes of ketones 20a-f with optically pure host 9b...

N-Methylation of 3 and reduction of the crystalline oxazolidinone 4 with lithium aluminum hydride was found to give a superior yield of DAIB (5) and a more easily purified product than exhaustive methylation of 2 with methyl iodide and reduction of the quaternary methiodide with Super-Hydride. Recently, a modified version of DAIB, 3-exo-morpholinoisoborneol MIB), was prepared by Nugent that is crystalline and that is reported to give alcohols in high enantiomeric excess from the reaction of diethylzinc with aldehydes. ... 

Spectrophotometric assays can be used for the estimation of the enantiosel-ectivity of enzymatic reactions. Reetz and coworkers tested 48 mutants of a lipase produced by epPCR on a standard 96-well microtiter plate by incubating them in parallel with the pure R- and S-configured enantiomers of the substrate (R/S-4-nitrophenol esters) [10]. The proceeding of the enzyme catalyzed cleavage of the ester substrate was followed by UV absorption at 410 nm. Both reaction rates are then compared to estimate the enantiomeric excess (ee-value). They tested 1000 mutants in a first run, selecting 12 of them for development of a second generation. In this way they were able to increase the enantiomeric excess from 2% for the first mutants to 88% after four rounds of evolutive optimization. 

The first example synthesized was based on the AHPC structure with (S)-cy-clohexylethylamine in the side-chain. The use of the more sterically hindered (S)-cyclohexylethylamine in the side-chain increased the enantiomeric excess from 83% ee (with (Sp,S)-5a to 90% ee with (Sp,S)-5b (complete conversion). The other diastereomer, (Pp,S)-5b, resulted in 94% yield and 87% ee. The ligand pair 6b, which is based on BHPC with (S)-t-butylethylamine in the side-chain, resulted in a matched/mismatched pair. The (Rp,S) diastereomer gave a 98% yield and an excellent 89% ee, but the (Sp,S) diastereomer produced only a 25% yield with a moderate 42% ee. The diastereomeric pair 6c, also based on BHPC 3 with (S)-naphthalen-l-ylethylamine in the side-chain, resulted similarly in a matched/mismatched pair with high activity, but only moderate enantiomeric excess. 

Shihawki observed a salt effect in this synthesis. Addition of two equivalents of sodium bromide increased the enantiomeric excess from 66% to 87%. 

Further illustrations of the value of isoxazole and Heck methodologies in flavone synthesis have been published (95ACS524) and a route to 3-aminoflavone-8-acetic acid has been described (95TL1845). The use of an imidazolidinone chiral auxiliary enables isoflavans to be formed in good yield and in high enantiomeric excess from phenacyl chlorides (95CC1317). 

It is more interesting that reduction of complex ketones could be dramatically improved by optimization of the reaction temperature. In the case of the phenoxyphenylvinyl methyl ketone (6), a 5-lipoxygenase inhibitor synthesis intermediate, we were able to improve the enantiomeric excess from the 80-85% range up to 96% by selection of the optimal temperature for the reduction. In this case, the temperature range for an acceptable enantiomeric excess is very narrow. Generally, Me-CBS is the best catalyst with borane complexes as reducing agent. 

Another class of peroxidases which can perform asymmetric sulfoxidations, and which have the advantage of inherently higher stabilities because of their non-heme nature, are the vanadium peroxidases. It was shown that vanadium bromoperoxidase from Ascophyllum nodosum mediates the production of (R)-methyl phenyl sulfoxide with a high 91% enantiomeric excess from the corresponding sulfide with H202 [38]. The turnover frequency of the reaction was found to be around 1 min-1. In addition this enzyme was found to catalyse the sulfoxidation of racemic, non-aromatic cyclic thioethers with high kinetic resolution [309]. 

Average enantiomeric excess from different libraries (entries 1 -10) or from a single library (entrie s 11-14). Enantiomeric excess from discrete ketone reduction. 

A chiral 3-methyl-1-phenylpalladium complex is isolated in enantiomeric excess from (S)-E-3-acetoxy-l-phenyl-1-butene. The result is in agreement with the oxidative addition proceeding with inversion on carbonThe r/ -benzylcompound XCII (cf. the corresponding Mo complex XV) is stable at RT, and is obtained from benzyl chloride and Pd atoms (from a metal vapor generator) ... 

It was found that lowering the reaction temperature from rt to — 10°C resulted in an increased enantiomeric excess (from 27% ee to 54% ee). Surprisingly, the addition of small amounts of water (ca. 20 mol %) also increased the chiral induction observed (up to 89% ee). 

Oppolzer and Tamura [460, 861, 1076] have recommended 1-chloro-l-ni-trosocyclohexane as an electrophile for preparation of nonracemic a-aminoacids. a-Aminoacids are formed with an excellent enantiomeric excess from sodium eno-lates ofN-acylsultams 1.134 (R = R CH by a sequence of nitrosylation, hydrolysis and reduction of the intermediate hydroxylamine, and cleavage of the auxiliary with LiOH (Figure 5.39). The stereoselectivity of tins process is interpreted by attack of the electrophile on the face opposite to the nitrogen lone pair of the Z-chelated enolate 5.58 (Figure 5.39). 

Lipase Enantioselectivity in hydrolysis of p-nitrophenyl 2-me-thyldecanoate Increase in enantiomeric excess from 2 % to 81 %... 

Esterase Enantioselectivity of hydrolysis of a sterically hindered 3-hydroxy ester Increase in enantiomeric excess from 0% to 25 %... 

In addition to baker s yeast, several systems that selectively reduce aliphatic ketones are now known. Lactic acid bacteria, e.g., Lactobacillus fermentum, Lactobacillus brevis or Leuconostoc paramesenteroides, reduce 2-pentanone or acetophenone in high yield (50- 100%) and high enantioselectivity (94-100% ee) to the (S )-configurated alcohols247. (5)-Alcohols are also obtained with high enantiomeric excess from 2-pentanone, 2-heptanone, 2-octanone and the substituted ketones 3-methyl-2-butanone and 4-methylpentane-2,3-dione by reduction with resting cells of the thermophilic archaebacterium Sulfolobus so/fataricus24s. 

EUROPT-1 modified in 3.4mM alkaloid gave ee = 41%(/ ) which was retained over the 5 h test period (Figure 3). This catalyst provides ee - 70%(/ ) in dichloromethane solution at 30 bar, and 65%(/ ) in ethanolic solution at 10 - 110 bar. That gas phase reaction may be less selective is to be expected from the absence of a rate enhancement. In the liquid phase, enantioselective reaction is so much faster than racemic reaction (factor 40) that the contribution to the enantiomeric excess from reaction at unmodified sites is small by comparison with that at enantioselective sites. By contrast, in the gas phase reaction, the rate of reaction at the modified surface is less than that at the mimodified surface, so the effect of reaction at racemic sites at a modified surface makes a larger contribution to the overall reaction. 

Copolymerisation of the monomeric divinyl substituted Mn complex with styrene and DVB. Enantioselective epoxidation of styrene and cts-P-styrene using various oxidants, Cis / trans ratio of epoxides range from 73 27 to 93 7 enantiomeric excesses from 4 to 41%. 

The most studied catalytic system is the one derived from 1,2-diamino-cyclohexane-derived Schiff base, presented for the first time by North and Belokon in 1998 for the cyanosilylation of aldehydes. In contrast to many catalysts known to date that require more than 10 mol% of loading and low temperatures, the catalyst 18 employed here was efficient at 0.1 mol% for a complete conversion at room temperature (0.01 mol% for 80% conversion. Scheme 7.14). Enantiomeric excesses from 30 to 86% were obtained from aromatic aldehydes and lower 44-46% enantiomeric excesses were observed from aliphatic ones (propanal and pivalaldehyde). 

Polymer-supported chiral p-hydro q amides, derived from the molecular chiral ligand 60, were also successfully used. High yields and enantio-selectivities were obtained with resin 61 (Figure 7.6). The supported ligand was reused 4 times, with a decrease of the enantiomeric excess (from 87 to 80% in the addition of phenylacetylene to benzaldehyde). The same p-hydro q amide was also grafted onto amorphous silica gel and the ligand 62 was reused five times with slight loss of enantioselectivity (from 78 to 75% enantiomeric excesses). ... 

This procedure, developed by Kagan, allows access to various types of chiral sulfoxides, such as f-butyl alkyl or t-butyl aryl sulfoxides, neither of which are available in high enantiomeric excess from other methods. 

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