enantioselective discrimination in NMR-based structure elucidations. This effect is
attributed to the selective inclusion of the enantiomer to the chiral host—cyclodextrin. Also, chiral lanthanides are used as chiral shift reagent in enantioselective
NMR-based investigations (Jiang et al. 1999; Blanc et al. 2005; Florini et al. 2010;
Brummond and Osbourn 2011; Aizawa et al. 2015). However, in contrast to chiral
lanthanide shift reagents, cyclodextrins cause non-equivalence even in the absence
of functional groups. Further examples including a detailed discussion on correlations between chemical shift non-equivalence and host–guest interactions between
racemic compounds and cyclodextrins can be found in the early monograph by
König (König 1992) and other more recent comprehensive books (Francotte and
Lindner 2006; Wenzel 2007, 2018).
6.3 Enantiomer-Selective Mass Spectrometry
Mass spectrometry is a technique that provides structural information based on the
molecular mass of compounds and their fragments when entered into the MS for
fragmentation. The substances entering the high vacuum of the ionisation chamber
are ionised chemicals and sorted into the ions based on their mass-to-charge ratio
(m/z). Mass spectrometry is, thus, not able to discriminate among enantiomers solely
by mass-selective detection. Only through method adjustments, the necessary
stereoselectivity is acquired. Usually, mass spectrometry is combined with chromatographic methods and, thus, used as sensitive detection technology after chromatographic separation (including enantiomer-selective chromatography). This
hyphenation technique is currently the most used analytical method for sensitive
quantification of pollutants and other bioactive organic compounds (Andrikopoulos
2002; Awad and El-Aneed 2013).
However, also direct modification on the mass spectrometric method without
hyphenation is reported for enantiomer-selective separation. Shizuma and
co-workers reported the direct separation of enantiomers of chiral alcohols by
creating diastereomeric complexes with the bistosylate of diethylene glycol
(Shizuma et al. 2009). Fast atomic bombardment (FAB) spectra were measured
and used for method optimisation and identification of the resulting diastereomeric
complexes. The here chosen method allowed the enantioselective discrimination of
each host in the mixture without further isolation.
The preparation of enantiomeric mixtures as a diastereomeric complex for
enantiomer-selective mass spectrometric structure elucidation has today developed
into a well-established method for enantiomer-selective structure elucidation of
small and complex molecules (Yao et al. 2000; Doan and Fujihara 2018).
Recently, ion trap or quadrupole mass spectrometry in combination with ion
mobility mass spectrometry (Dwivedi et al. 2006; Kanu et al. 2008) is applied for
enantioselective separation. The enantiomer separation in ion mobility mass spectrometry by interacting of the enantiomeric analytes with chiral gases (i.e. S-(+)-2butanol) and the respective creation of reversible diastereomeric complexes was
92
6 Other Methods for the Elucidation of Molecular Structures and Mechanistic. . .
attributed to the selective inclusion of the enantiomer to the chiral host—cyclodextrin. Also, chiral lanthanides are used as chiral shift reagent in enantioselective
NMR-based investigations (Jiang et al. 1999; Blanc et al. 2005; Florini et al. 2010;
Brummond and Osbourn 2011; Aizawa et al. 2015). However, in contrast to chiral
lanthanide shift reagents, cyclodextrins cause non-equivalence even in the absence
of functional groups. Further examples including a detailed discussion on correlations between chemical shift non-equivalence and host–guest interactions between
racemic compounds and cyclodextrins can be found in the early monograph by
König (König 1992) and other more recent comprehensive books (Francotte and
Lindner 2006; Wenzel 2007, 2018).
6.3 Enantiomer-Selective Mass Spectrometry
Mass spectrometry is a technique that provides structural information based on the
molecular mass of compounds and their fragments when entered into the MS for
fragmentation. The substances entering the high vacuum of the ionisation chamber
are ionised chemicals and sorted into the ions based on their mass-to-charge ratio
(m/z). Mass spectrometry is, thus, not able to discriminate among enantiomers solely
by mass-selective detection. Only through method adjustments, the necessary
stereoselectivity is acquired. Usually, mass spectrometry is combined with chromatographic methods and, thus, used as sensitive detection technology after chromatographic separation (including enantiomer-selective chromatography). This
hyphenation technique is currently the most used analytical method for sensitive
quantification of pollutants and other bioactive organic compounds (Andrikopoulos
2002; Awad and El-Aneed 2013).
However, also direct modification on the mass spectrometric method without
hyphenation is reported for enantiomer-selective separation. Shizuma and
co-workers reported the direct separation of enantiomers of chiral alcohols by
creating diastereomeric complexes with the bistosylate of diethylene glycol
(Shizuma et al. 2009). Fast atomic bombardment (FAB) spectra were measured
and used for method optimisation and identification of the resulting diastereomeric
complexes. The here chosen method allowed the enantioselective discrimination of
each host in the mixture without further isolation.
The preparation of enantiomeric mixtures as a diastereomeric complex for
enantiomer-selective mass spectrometric structure elucidation has today developed
into a well-established method for enantiomer-selective structure elucidation of
small and complex molecules (Yao et al. 2000; Doan and Fujihara 2018).
Recently, ion trap or quadrupole mass spectrometry in combination with ion
mobility mass spectrometry (Dwivedi et al. 2006; Kanu et al. 2008) is applied for
enantioselective separation. The enantiomer separation in ion mobility mass spectrometry by interacting of the enantiomeric analytes with chiral gases (i.e. S-(+)-2butanol) and the respective creation of reversible diastereomeric complexes was
92
6 Other Methods for the Elucidation of Molecular Structures and Mechanistic. . .