Mass pseudo-racemic mixture

One of the critical aspects of this approach is that two different experiments have to be performed between which the particular instrument conditions must be carefully kept constant in order not to affect the intensity ratios. This problem can be overcome by the enantiomer-labeled guest method [47]. It is based on the mass spectrometric examination of one enantiomer of the host with a pseudo-racemic mixture of the guest. In order to be able to detect both diastereomers separately, one enantiomer of the guest must be isotopically labeled, usually with deuterium. In the same experiment, both diastereotopic complexes are formed and their intensities can be compared directly. However, the stereochemical effect might additionally be superimposed by an unknown isotope effect. A way to separate stereochemical and isotope effects is to perform the same experiment with the second host enantiomer [4B]. In one experiment both stereochemical and isotope effects disfavor the same complex and thus work in the same direction. In the other experiment, they partly cancel each other. If both experiments have been performed, one can use the two experimental values for the intensity ratios of both diastero-meric complexes to deconvolute both effects [49]. 

Horeau published in 1982 a pioneering work on the use of mass spectrometry to evaluate the extent of KR in the esterification of racemic alcohols by a chiral anhydride. The principle was to label by deuterium one of the enantiomers of the alcohol and use it to prepare a pseudo-racemic mixture of the alcohol [102]. Mass spectrometry revealed which enantiomer reacted preferentially with the chiral reagent... 

Reetz and coworkers developed a highly efficient method for screening of enantioselectivity of asymmetrically catalyzed reactions of chiral or prochiral substrates using ESI-MS [60]. This method is based on the use of isotopically labeled substrates in the form of pseudo-enantiomers or pseudo-prochiral compounds. Pseudo-enantiomers are chiral compounds which are characterized by different absolute configurations and one of them is isotopically labeled. With these labeled compounds two different stereochemical processes are possible. The first is a kinetic separation of a racemic mixture, the second the asymmetric conversion of prochiral substrates with enantiotopic groups. The conversion can be monitored by measuring the relative amounts of substrates or products by electrospray mass spectrometry. Since only small amounts of sample are required for this method, reactions are easily carried out in microtiter plates. The combination of MS and the use of pseudo-enantiomers can be used for the investigation of different kinds of asymmetric conversion as shown in Fig. 3 [60]. 

Reetz et al. [103] extended this approach. He reported the principle of a method based on electrospray ionization mass spectrometry (ESI-MS) enabling the determination of enantioselectivity of catalytic or stoichiometric asymmetric reactions. The method involves the reaction of a chiral reagent or catalyst with an equimolecular mixture of pseudo enantiomers, one isotopically labelled and the other non-labelled, simulating a racemate. 

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