Enantiomer isolation excess, determination

Reaction of [FeCp(C6Me6)][PF6] [33-35] with excess KOH (or tBuOK) in THF or DME and excess alkyl iodide, allyl bromide, or benzyl bromide leads to one-pot hexasubstitution (Scheme 5a) [36-38]. With allyl bromide (or iodide) in DME, the hexaallylated complex has been isolated and its X-ray crystal structure determined, but the extremely bulky dodeca-allylation [52] product can also be reached when the reaction time is extended to two weeks at 40 °C. The chains are fixed in a directionality such that conversion to the enantiomer is not possible, thus making the metal complex chiral (Scheme 5b). 

This concept was also recently extended by Reetz et al. to the resolution of phenylethylamine [12]. In this case, an immobilised lipase and ethyl acetate as acyl donor are used the non-acylated (S)-enantiomer of the amine is racemized in situ by palladium on charcoal. After 8 days -the metal catalyzed racemization is again likely to he the rate-determining step - (/ )-A-acetyl-phenylethylamine is isolated in 64 % yield and 99 % enantiomeric excess. 

Chromatographic enantioseparation of chiral xenobiotics and their metabolites is a versatile tool for process studies in marine and terrestrial ecosystems [235]. In 1994, three papers focused on the enantioselective determination of toxaphene components [120,236,237]. Buser and Muller found that technical toxaphene mixtures are not necessarily racemic [237]. This observation was supported after isolation of non-racemic B7-1453 from the product Melipax which had an excess of ca. 25% of the dextrorotary enantiomer [27, 238]. The enantioselective separation of toxaphene components is almost restricted to chiral stationary phases (CSPs) based on randomly derivatized ferf-butyldimethyl-silylated /1-cyclodextrin (commercially available from BGB Analytik, Adliswil, Switzerland). So far, only a few toxaphene components were enantioseparated on other CSPs [239, 240]. Some of these CSPs are not well defined as well, and for this reason a test mixture called CHIROTEST X was suggested for initial column testing [241],... 

To a flame-dried round bottom flask containing racemic 1 -indanol (2 mmol, 270 mg) dissolved in diethyl ether (10 mL) was added succinic anhydride (2 mmol, 200 mg a twofold excess since only one enantiomer reacts), followed by immobilized C. antarctica lipase B (Novozym 435, 300 mg can be reduced to 6 mg). The suspension was stirred at room temperature for 22-24 h to reach -50% conversion (44% in this example) as determined by HPLC of the mixture on a Chiralcel OD-H capillary column. The reaction was stopped by filtration to remove the immobilized enzyme that was washed with ethyl ether, dried at room temperature in air and saved for reuse up to seven times. The reaction rate decreases with subsequent uses, but the enantiose-lectivity remains high. The combined filtrates were extracted with aqueous sodium carbonate (1 M, 3 X 5 mL) and water (1x5 mL) to remove the succinate. The remaining ethyl ether solution containing unreacted 1 -indanol was concentrated by rotary evaporation and purified by chromatography on silica gel eluted with hexane/ethyl acetate 80 20 - 48% isolated )deld of (S)-l-indanol, 79% ee. Enantiomeric purity was measured after acetylation of the alcohol (Ac O, DMAP, NEt ) by HPLC on a Chiralcel OD-H capillary column. To recover the fast-reacting enantiomer, the combined aqueous extract (—20 mL) was extracted with ethyl ether (2x5 mL). Sodium hydroxide (2 g, 50 mmol) was added to the aqueous phase and stirred for 6 h at room temperature. The solution was extracted with dichloromethane (3X5 mL), the combined extracts washed with water (5 mL), dried over Na SO, concentrated by rotary evaporation and purified by silica gel chromatography 25% isolated yield (R)-l-indanol, >99% ee. 

The methods described in Section 6.9 are very useful for determining optical purities (enantiomeric excesses), but it is usually not possible to determine with certainty the absolute configuration of the major enantiomer present unless one has access to authentic samples of each pure enantiomer. This is rarely the case in natural product isolation or synthesis research. In 1973, Mosher described a method... 

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