A comprehensive examination of the self-disproportionation of enantiomers (SDE) of chiral amides via achiral, laboratory-routine, gravity-driven column chromatography

Article abstract of DOI:10.1039/c4ra13928c

This work explores the self-disproportionation of enantiomers (SDE) of chiral amides via achiral, gravity-driven column chromatography as typically used in laboratory settings. The major findings of this work are: (1) the remarkable persistence and high magnitude of the SDE for the analytes under a variety of conditions, including polar solvents and different achiral stationary phases and (2) the notable generality of the SDE phenomenon as it occurs for a wide range of chiral amide substrates and even for a broad range of starting ee. This last aspect is unusual and not commonly observed. The key conclusion of this work is that it judiciously conveys the predictability of the SDE for chiral amides under the routine conditions of achiral chromatography. These results are consequently of concern for practitioners in the area of catalytic asymmetric synthesis involving chiral amides as intermediates or products and the inferents need to be taken extremely seriously by workers in the field.

Full text of DOI:10.1039/c4ra13928c

RSC Advances
View Article Online
View Journal | View Issue
PAPER
A comprehensive examination of the self-
disproportionation of enantiomers (SDE) of chiral
amides via achiral, laboratory-routine, gravity-
driven column chromatography†
Cite this: RSC Adv., 2015, 5, 2988
a
b
a
c
d
Yuya Suzuki, Jianlin Han, Osamu Kitagawa, Jose Luis Acena, Karel D. Klika*
´
˜
ce
and Vadim A. Soloshonok*
This work explores the self-disproportionation of enantiomers (SDE) of chiral amides via achiral, gravity-
driven column chromatography as typically used in laboratory settings. The major findings of this work
are: (1) the remarkable persistence and high magnitude of the SDE for the analytes under a variety of
conditions, including polar solvents and different achiral stationary phases and (2) the notable generality
of the SDE phenomenon as it occurs for a wide range of chiral amide substrates and even for a broad
range of starting ee. This last aspect is unusual and not commonly observed. The key conclusion of this
work is that it judiciously conveys the predictability of the SDE for chiral amides under the routine
conditions of achiral chromatography. These results are consequently of concern for practitioners in the
area of catalytic asymmetric synthesis involving chiral amides as intermediates or products and the
inferents need to be taken extremely seriously by workers in the field.
Received 5th November 2014
Accepted 3rd December 2014
DOI: 10.1039/c4ra13928c
www.rsc.org/advances
2,12,13
for the phenomenon.
By far and away the majority of cases
Introduction
appear to involve intermolecular interactions forming homo-
1
8,11,12,14
The self-disproportionation of enantiomers (SDE) describes and heterochiral associates based on hydrogen bonding,
any process under achiral conditions which transforms a non- but other cases based on p-stacking or dipole–dipole inter-
racemic sample of a chiral compound into fractions contain- actions
4,15
16,17
have been noted. Of particular note, it has been
ing varying – enriched and depleted – proportions of the shown that optical purication based on the SDE phenomenon
enantiomers in comparison with the enantiomeric composition for some compounds can rival conventional recrystallization in
2
6c,d
of the starting sample. Since the initial observations of SDE via performance and practical application.
3
4
sublimation and achiral chromatography, numerous papers
have reported this phenomenon to occur via sublimation,
achiral chromatography, and even by distillation.
It is worth noting the predictions resulting from mathe-
matical modeling that have been made for the SDE phenom-
In addi- enon in idealized cases where only a single intermolecular
tion to the general SDE reviews, there are also two specic interaction is present and only one structural entity is formed,
5
18
6
6a,7
8,9
10,11
reviews
on the phenomenon via achiral chromatography. e.g. dimer formation. Firstly, baseline separation between the
The underlying premise is that dimeric homo- or heterochiral rst eluting component (e.g. the excess enantiomer) and the
associations or other higher-order aggregates are responsible second eluting component is not possible. Secondly, due to
being unable to attain baseline separation and the asymptotic
convergence of the rst eluting component, it is not possible to
separate out all of the rst eluting component from the sample
a
Department of Applied Chemistry, Shibaura Institute of Technology, 3-7-5 Toyosu,
Kohto-ku, Tokyo 135-8548, Japan
b
(i.e., for example, obtaining all of the excess enantiomer from
the racemic portion if the excess enantiomer is the rst eluting
School of Chemistry and Chemical Engineering, Nanjing University, 210093 Nanjing,
China
c
Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque component). In practical terms though, it is possible to obtain a
Country UPV/EHU, Paseo Manuel Lardiz a´ bal 3, 20018 San Sebasti a´ n, Spain.
large proportion of it. Thirdly, it is not possible at all to obtain
the second eluting component completely free of the rst
eluting component due to the asymptotic convergence of the
E-mail: vadym.soloshonok@ehu.es; Fax: +34 943 015270; Tel: +34 943 015177
d
Molecular Structure Analysis, German Cancer Research Center (DKFZ), Im
Neuenheimer Feld 280, D-69009 Heidelberg, Germany. E-mail: klikakd@yahoo.co.

rst eluting component, though in practice this can be incon-
uk; Fax: +49 6221 42 2995; Tel: +49 6221 42 4515
e
IKERBASQUE, Basque Foundation for Science, Mar ´ı a D ´ı az de Haro 3, 48013 Bilbao, sequential since the level of “contamination” becomes negli-
Spain
gible as the content of the rst eluting component converges to
zero. However, it is possible in theory to obtain fractions
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c4ra13928c
1
2988 | RSC Adv., 2015, 5, 2988–2993
This journal is © The Royal Society of Chemistry 2015

View Article Online
Paper
RSC Advances
containing the rst eluting component completely free of the
second eluting component, and this is not wholly dependent on
a high starting ee value.
As part of our ongoing investigation into the processes and
17
interactions leading to SDE via chromatography, in this study
we examine a set of amides in a similar detailed fashion to the
previous study by the adjustment of various parameters, e.g.
solvent polarity changes, other chromatographic parameters,
samples of varying initial ee, and varying structure of the ana-
lyte, to gauge the sensitivity of the SDE to the prevailing
17
conditions. The previous study was concerned with the
behavior of methyl n-pentyl sulfoxide (MPS) (and as an exten-
sion, to chiral sulfoxides generally), a compound whose inter-
molecular interactions are based on dipole–dipole interactions.
By contrast, the intermolecular interactions of the amides
examined here are based on the more commonly ascribed
hydrogen bonding.
Fig. 1 The set of amides examined in this study.
realized our worries; thus, compound 1, of 72.3% ee, when
subjected to routine column chromatography yielded initial
fractions highly enriched in the excess enantiomer (>93% ee)
while the nal fractions were alternatively drastically depleted
in the excess enantiomer (<45% ee). One may agree that this
experiment underscores the scientic signicance of this study
and its general importance for organic chemistry and asym-
metric synthesis. Currently, there is not yet an established
protocol regarding the conduct of a systematic SDE study, but
what is clear is that it is needed to (1) determine how the SDE
phenomenon depends on the chromatographic conditions,
thereby allowing chemists some degree of control over it, and
6d
In a previous examination of chiral amides, we were able to
demonstrate a very high magnitude for the SDE by medium
pressure liquid chromatography (MPLC). Considering that
chiral amides are one of the most prevalent classes of organic
intermediates, it is of vital importance to know if a sizeable SDE
could also readily occur under the routine conditions of achiral
chromatography as chiral amides are some of the most
commonly used intermediates in asymmetric synthesis and are
usually puried by achiral column chromatography as part of
common laboratory practice. Thus, if a sizeable magnitude of
the SDE is indeed observed under routine laboratory chroma-
tography, this should be brought to the attention of workers in
the eld and the appropriate precautions enacted in handling
research samples and, in particular, to avoid possible erroneous
interpretation of the results of catalytic asymmetric reactions.
This question has high scientic interest with regards to the
generality and understanding of the SDE phenomenon as well
as inferences for its predictability.
(2) ascertain its generality for chiral amides in terms of
predictability and the precautions required for dealing with this
class of chiral organic compounds.
With these considerations in mind, we decided to examine
the effect of solvent polarity whereby the ratio of hexane to ethyl
8,11,12,14
acetate was varied. It was assumed
that a more polar
eluent might disrupt the homo- and heterochiral interactions
during the chromatography and therefore quench the SDE
phenomenon. With this aim, we conducted a series of experi-
ments varying the ratio of hexane to ethyl acetate from 5 : 3 to
In this work, we systematically examined various conditions
for the gravity-driven column chromatography of a set of chiral
amides with the variance of a number of parameters other than
the substrate structure. Oen, it is the case that only a small
range of ee values lead to a high Dee, and therefore potentially
5
: 6. Analysis of the collected fractions for each chromato-
graphic run showed that the early eluting fractions were quite
uniformly enantiomerically enriched in comparison to the
starting sample while the later eluting fractions were corre-
spondingly enantiomerically depleted (Fig. 2).
2
to the obtainment of enantiomerically pure fractions. Conse-
The rst striking observation was that the magnitude of the
SDE (Dee, dened as the difference between the rst and nal
fractions) was effectively impervious to the solvent changes, a
result which is highly unexpected and contrary to previous
observations. As mentioned above, it has so far been a basic
rationale that with higher solvent polarity, the breakup of
associates can be anticipated leading to a muting of the SDE
phenomenon. Although elution is considerably accelerated with
an increase in the content of the ethyl acetate, the ee of the
initial fraction remains high in all cases, indeed, inexplicably it
is even highest in the chromatographic run using the most
polar of the eluent mixes. A second point of note is that, e.g. in
the chromatographic run using hexane to ethyl acetate in a ratio
of 5 : 3, the ee does not drop continuously and both the second
and the twelh fractions exhibit a rise in the ee relative to the
preceding fraction. These aberrations have previously been
quently, it has mistakenly been believed that a high initial ee
was therefore required to obtain an enantiomerically pure
fraction, but we demonstrate herein that this need not be the
case. Furthermore, quite interestingly, we show that the
dependency on initial ee for these compounds was much
reduced and high ee values for the rst eluting fraction were
obtained for a wide range of samples of varying initial ee.
Results and discussion
The structures of the amides examined in this work are pre-
sented in Fig. 1. We initiated our study using compound 1 in the
test experiments to see if the SDE can be observed under routine
laboratory-run, gravity-driven chromatography. For this test we
used arbitrary conditions derived from our previous experience
17
with the SDE study of chiral sulfoxides. The rst test run fully
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 2988–2993 | 2989

View Article Online
RSC Advances
Paper
formation of analyte associates, increasing the amount of the
analyte can favor the formation of the required associates. Since
substantial changes were not observed, it can be assumed that
the optimum concentration of the analyte has been reached and
above this level no further improvement will be forthcoming.
Very high concentrations might even lead to a decrease in the
magnitude of the SDE, though this has never been observed and
it has always been the case that either the Dee increased, or, as
in this instance, essentially the same Dee was obtained.
The second examination involved increasing the amount of
silica gel to attain a column length double that initially used
(
run c, Fig. 3). SDE via chromatography differs fundamentally
Fig. 2 The effect of solvent polarity on the SDE of compound 1 using a
sample of 72.3% ee. The ratio of hexane to ethyl acetate is indicated for
from the usual chromatography of analytes in that in the latter
each run. For each run, 50 mg of compound 1 per 6.3 g of silica gel case, resolution improves indenitely with increasing column
were used (60 A˚ pore size, 40–63 mm particle size) on a column 20
mm in diameter and length 45 mm. Each collected fraction consisted
of 10 mL of eluent.
length, albeit with an ever-decreasing gain in resolution and at
the cost of ever-increasing broader peaks. Since SDE via chro-
matography is dependent on analyte–analyte interactions,
dilution from passage along a column only serves to reduce
1
7
these interactions and hence the phenomenon reaches a limit
in terms of performance. In this case, as also observed previ-
described as “kinks” and allude to the complex nature of the
processes leading to the SDE phenomenon or to drastic changes
in the local concentrations, a point discussed in detail further
on.
17
ously, this limit is easily attained as the run with a longer
column failed to improve or alter the magnitude of the SDE to a
signicant extent aer taking into account the extended elution
prole due to the longer column length engaged.
As a result of these measurements, for all subsequent chro-
matographic runs, it was considered judicious to use an equal
ratio of hexane to ethyl acetate (5 : 5) as the eluent.
In our next set of experiments, the rst examination of
varying the chromatographic conditions was to increase the
amount of compound 1 loaded onto the column from 50 mg to
00 mg whilst keeping all other parameters constant (run b,
Fig. 3). The result was that an almost identical elution prole
was obtained. Since the SDE phenomenon is dependent on the
The third examination involved using silica gel of larger
particle size, 60–200 mm rather than 40–63 mm (run d, Fig. 3).
Again, discernible differences amenable to meaningful inter-
pretation were not observed. This was a surprising result, and in
17
contrast to previous observations it must be noted, as the
chromatographic performance is usually dependent on the
particle size of the stationary phase – which may have as much
to do with reduced inherent chromatographic capability of the
stationary phase as it does with a change in system dimensions
relevant to SDE via chromatography – but it indicates that for
SDE via chromatography, the formation of analyte associates is
probably as much dependent on the solution phase as it is on
the adsorbed phase. The initial thinking was that a larger grain
size would provide larger interstitial volumes, which in turn can
result in a reduced concentration of the analyte in these voids,
thus affecting the magnitude of the SDE result. However, since
the previous run (run b) indicated that the system is already at a
high optimum in terms of concentration for this particular
substrate and its intermolecular interactions, it may be that a
relatively small alteration resulting from interstitial volume
changes would not be sufficient to result in discernible effects.
The dependency on the chromatographic performance of the
system can also be very much substrate dependent as well as on
1
Fig. 3 The effect of other chromatographic parameters on the SDE of
compound 1 using a sample of 72.3% ee. For each run, the ratio of
hexane to ethyl acetate was 5 : 5. Runs: (a) 50 mg of compound 1 per
.3 g of silica gel were used (60 A˚ pore size, 40–63 mm particle size) on
a column 20 mm in diameter and length 45 mm (i.e. the same
17
the type of interactions involved; in the previous study with
sulfoxides, the compound's intermolecular interactions are
based on dipole–dipole interactions.
6
The nal examination involved using aluminum oxide
conditions as in Fig. 2); (b) 100 mg of compound 1 was applied to the instead of silica as the stationary phase (run e, Fig. 3). Here the
column under otherwise identical conditions; (c) 12.6 g of silica gel was
used under otherwise identical conditions (resulting in a column
length of 90 mm); (d) silica gel of 60–200 mm particle size was used
under otherwise identical conditions; and (e) aluminum oxide (neutral,
grade I) was used instead of silica gel under otherwise identical
conditions. Each collected fraction consisted of 10 mL of eluent.
magnitude of the SDE was markedly reduced in comparison to
the results obtained with silica gel, though still notable none-
theless. But the result, given that the magnitude of the SDE was
effectively impervious to all other parameter changes, lends
19
credence to the premise of Klika et al. whereby it was asserted
2990 | RSC Adv., 2015, 5, 2988–2993
This journal is © The Royal Society of Chemistry 2015

View Article Online
Paper
RSC Advances
that the SDE phenomenon is not just a question of a preference
between homo- and heterochiral dimers, but the relative
stability of these homo- and heterochiral dimers as the envi-
ronment changes, e.g. from solution in the eluent in the inter-
stitial spaces to the pores of the stationary phase. That is, a
perturbation in aggregation behavior between the free mole-
cules and the homo- and heterochiral dimers can arise from the
different environments of the different stationary phases in use.
The observed change in SDE behavior of compound 1 upon
changing the stationary phase from silica gel to aluminum
oxide supports this assertion.
As before, it is noted that there is a substantial kink in the
early part of the elution prole for aluminum oxide. Such kinks
6
b,15,17,20
occasionally occur at the front end of the elution prole,
Fig. 4 The effect of the sample initial ee on the SDE of compound 1.
For each run, the ratio of hexane to ethyl acetate was 5 : 5 under
otherwise identical conditions as described in Fig. 1. The initial ee of
the sample is indicated for each run. Each collected fraction consisted
of 10 mL of eluent.
17
17
but may also occur in the middle (vide infra) as well as the tail
vide supra) and even occur multiple times during the course of
the elution. By far the most dramatic example, so extreme in
fact it has been considered a double SDE via chromatography
(
17
19
event, was observed during the chromatography of spiro-
21
brassinins. Such aberrant behavior or any deviation from ideal
indicates that the system is far from a simple and idealized one
that can be described by one intermolecular interaction and one
type of transitory structure such as dimers. Thus oligomer
formation, in addition to dimer formation, or alternative
binding modes must be occurring whenever aberrant behavior
examined all nine compounds 1–9 displayed in Fig. 1 using
similar initial ee's in each case. The results are portrayed in
Fig. 5. For compounds 1 and 4–9, the Dee values are reasonable
to high. For compounds 2 and 3, however, with the two lowest
values for Dee, 6.3 and 10.9%, respectively, clearly there must be
steric hindrance from the large groups adjacent to the carbonyl
impeding the formation of any dimers, hence precluding
manifestation of the SDE phenomenon to a high degree. Thus,
as long as the substituents do not sterically impede the
formation of hydrogen bonding between the amide groups, SDE
via chromatography appears to be impervious to the substrate
structure for this class of compounds. Notable again is that
kinks are evident in the elution proles for some of the
compounds under these conditions in both the middle
19,22
is observed. The latter explanation has been proposed,
with
some legitimacy, to account for the dramatic behavior of the
21
spirobrassinins. Thus it is clear that the graphical represen-
tations are not ideal with respect to mathematical modeling
assuming a single intermolecular interaction and the formation
11,12
of only one type of transitory aggregate structure
and/or the
differential formation of the dimers under the various envi-
ronments of the chromatography.
Although the occurrence of the SDE phenomenon does
depend to a degree on the starting ee of a sample, previous
(compounds 2 and 8) and in the tail (compounds 5 and 7)
sections of the elution proles.
2,23
investigations have implied that to obtain a sample with high
optical purity via SDE it was necessary to utilize a sample of high
ee, but this need not be the case. Nevertheless, oen it is the
case that only a small range of ee values lead to a high Dee and
therefore potentially to the obtainment of enantiomerically
2
pure fractions, this only adding to the mistaken belief that a
high initial ee was required to obtain an enantiomerically pure
fraction. Here, interestingly, the dependency on initial ee was
reduced and high ee values for the rst eluting fraction were
obtained for a wide range of samples of varying initial ee. The
results are portrayed in Fig. 4 for a range of initial ee's, from 12–
90%. Essentially, a set of runs spanning >35% initial ee (54–90%
initial ee) all provided similar results in terms of high enan-
tiomeric purity for the rst eluting fraction. Of note, the largest
magnitudes for the Dee, 30–40%, were obtained for initial ee's
from 45–72% ee, thus even the Dee spans a considerable range.
Fig. 5 The SDE behavior of the compounds 1–9. For each run, the
Overall though, and truly quite remarkably, regardless of appropriate ratio of hexane and ethyl acetate was used under other-
wise identical conditions as described in Fig. 1 with the compound
number indicated for each run. The initial ee's of the samples with the
the conditions applied, generally the same robust and
unquenchable effect of the SDE phenomenon was observed for
attained Dee's in parentheses were: 1, 72.3 (39.9); 2, 69.6 (6.3); 3, 68.7
compound 1.
(
(
10.9); 4, 69.9 (31.2); 5, 72.0 (28.9); 6, 72.5 (24.7); 7, 70.2 (24.5); 8, 72.9
17.6); and 9, 75.0% (21.8%). Each collected fraction consisted of 10 mL
To complete our investigations and demonstrate the robust
generality of the SDE phenomenon for these amides, we of eluent.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 2988–2993 | 2991

View Article Online
RSC Advances
Paper
4
K. C. Cundy and P. A. Crooks, J. Chromatogr., 1983, 281, 17–
Conclusions
33.
In conclusion, we have described the results of an investigation
into the SDE phenomenon via gravity-driven chromatography
over achiral silica gel for a set of amides. We demonstrated that
it is possible to obtain the compounds in high optical purity
under various conditions. Indeed, it was found that the SDE
phenomenon for these compounds could be observed under all
applied conditions, including for a broad range of starting ee.
This latter aspect is unusual and not commonly observed. Most
importantly however, SDE via chromatography has a consider-
able and noticeable effect on the ee of sample by the standard,
routine column chromatography conditions that are in use in
any research laboratory. These results are consequently of
considerable concern for workers in the eld of asymmetric
synthesis concerned with chiral amides as intermediates if they
are unaware of the problem. On the other hand, it is highly
probable that optical purication based on the SDE phenom-
enon represents a simple, convenient, and inexpensive method
for the optical purication of this class of compounds with a
high degree of prociency. These results should serve as a
warning to organic chemists as the SDE for amides cannot be
effectively controlled and occurs under virtually any conditions
and for, as we anticipate, virtually any structural type of chiral
amide.
The SDE for these chiral amides can be explained by the
strong tendency of these compounds to form homo- and het-
erochiral dimers by hydrogen bonding interactions with the
differing chromatographic behavior of the entities the under-
lying mechanism responsible for the SDE phenomenon. Aber-
rant SDE behavior, however, was also noted in that the ee did
not always fall continuously during the progression of the
chromatography, and this was attributed to the complexity of
the system at hand which cannot be described in simple terms
such as the formation only of homo- and heterochiral dimers
based on a single interaction. It is possible that higher-order
aggregates might also be involved to explain the deviation of
behavior from ideal as well as the premise that it is the
perturbation in aggregation behavior between the free mole-
cules and the homo- and heterochiral dimers which can arise
5 (a) J. Han, D. J. Nelson, A. E. Sorochinsky and
V. A. Soloshonok, Curr. Org. Synth., 2011, 8, 310–317; (b)
V. A. Basiuk, T. Y. Gromovoy, A. A. Chuiko,
V. A. Soloshonok and V. P. Kukhar, Synthesis, 1992, 449–
451; (c) V. A. Soloshonok, H. Ueki, M. Yasumoto,
S. Mekala, J. S. Hirschi and D. A. Singleton, J. Am. Chem.
Soc., 2007, 129, 12112–12113; (d) M. Yasumoto, H. Ueki,
T. Ono, T. Katagiri and V. A. Soloshonok, J. Fluorine Chem.,
2010, 131, 535–539; (e) M. Albrecht, V. A. Soloshonok,
L. Schrader, M. Yasumoto and M. A. Suhm, J. Fluorine
Chem., 2010, 131, 495–504; (f) M. Yasumoto, H. Ueki and
V. A. Soloshonok, J. Fluorine Chem., 2010, 131, 266–269; (g)
M. Yasumoto, H. Ueki and V. A. Soloshonok, J. Fluorine
Chem., 2010, 131, 540–544; (h) H. Ueki, M. Yasumoto and
V. A. Soloshonok, Tetrahedron: Asymmetry, 2010, 21, 1396–
1400; (i) A. V. Tarasevych, A. E. Sorochinsky, V. P. Kukhar,
A. Chollet, R. Daniellou and J.-C. Guillemin, J. Org. Chem.,
2013, 78, 10530–10533; (j) A. Bellec and J.-C. Guillemin,
Chem. Commun., 2010, 46, 1482–1484; (k) A. Bellec and
J.-C. Guillemin, J. Fluorine Chem., 2010, 131, 545–548.
6 (a) J. L. Ace n˜ a, A. E. Sorochinsky, T. Katagiri and
V. A. Soloshonok, Chem. Commun., 2013, 49, 373–375; (b)
S. Ogawa, T. Nishimine, E. Tokunaga, S. Nakamura and
N. Shibata, J. Fluorine Chem., 2010, 131, 521–524; (c)
A. E. Sorochinsky, T. Katagiri, T. Ono, A. Wzorek,
J. L. Ace n˜ a and V. A. Soloshonok, Chirality, 2013, 25, 365–
368; (d) T. Nakamura, K. Tateishi, S. Tsukagoshi,
S. Hasimoto, S. Watanabe, V. A. Soloshonok, J. L. Ace n˜ a
and O. Kitagawa, Tetrahedron, 2012, 68, 4013–4017; (e)
R. M. Carman and K. D. Klika, Aust. J. Chem., 1991, 44,
895–896.
7 (a) B. Koppenhoefer and U. Trettin, Fresenius' Z. Anal. Chem.,
1989, 333, 750–750; (b) T. Katagiri, C. Yoda, K. Furuhashi,
K. Ueki and T. Kubota, Chem. Lett., 1996, 25, 115–116.
8 J. Martens and R. Bhushan, Helv. Chim. Acta, 2014, 97, 161–
187.
9 A. E. Sorochinsky and V. A. Soloshonok, Top. Curr. Chem.,
2013, 341, 301–339.
from the different environments that is an important factor in 10 J. Martens and R. Bhushan, J. Liq. Chromatogr. Relat.
the SDE process.
Technol., 1992, 15, 1–27.
1
1
1 V. A. Soloshonok, C. Roussel, O. Kitagawa and
A. E. Sorochinsky, Chem. Soc. Rev., 2012, 41, 4180–4188.
2 V. Nieminen, D. Yu. Murzin and K. D. Klika, Org. Biomol.
Chem., 2009, 7, 537–542.
Acknowledgements
The authors gratefully acknowledge nancial support from
IKERBASQUE, Basque Foundation for Science; the Basque 13 V. A. Soloshonok and D. O. Berbasov, Chim. Oggi, 2006, 24,
Government (SAIOTEK S-PE13UN098), and Hamari Chemicals
Osaka, Japan).
44–47.
(
14 A. E. Sorochinsky, J. L. Ace n˜ a and V. A. Soloshonok,
Synthesis, 2013, 45, 141–152.
1
5 V. J. Mayani, S. H. R. Abdi, R. I. Kureshy, N. H. Khan,
S. Agrawal and R. V. Jasra, Chirality, 2009, 21, 255–261.
Notes and references
1
The applied terminology has been much discussed and 16 W.-L. Tsai, K. Hermann, E. Hug, B. Rohde and A. S. Dreiding,
debated and is used herein as recommended by K. D. Klika Helv. Chim. Acta, 1985, 68, 2238–2243.
and V. A. Soloshonok, Helv. Chim. Acta, 2014, 97, 1583–1589. 17 A. Wzorek, K. D. Klika, J. Drabowicz, A. Sato, J. L. Ace n˜ a and
2
3
V. A. Soloshonok, Angew. Chem., Int. Ed., 2006, 45, 766–769.
G. Pracejus, Liebigs Ann. Chem., 1959, 622, 10–22.
V. A. Soloshonok, Org. Biomol. Chem., 2014, 12, 4738–4746.
2992 | RSC Adv., 2015, 5, 2988–2993
This journal is © The Royal Society of Chemistry 2015

View Article Online
Paper
1
RSC Advances
8 (a) E. Gil-Av and V. Schurig, J. Chromatogr. A, 1994, 666, 519– 20 V. A. Soloshonok and D. O. Berbasov, J. Fluorine Chem., 2006,
25; (b) R. Baciocchi, G. Zenoni, M. Mazzotti and 127, 597–603.
M. Morbidelli, J. Chromatogr. A, 2002, 944, 225–240; (c) 21 (a) M. Such ´y , P. Kutschy, K. Monde, H. Goto, N. Harada,
5
R. Baciocchi, M. Mazzotti and M. Morbidelli,
J. Chromatogr. A, 2004, 1024, 15–20; (d) R.-M. Nicoud,
J.-N. Jaubert, I. Rupprecht and J. Kinkel, Chirality, 1996, 8,
M. Takasugi, M. Dzurilla and E. Balentov ´a , J. Org. Chem.,
2001, 66, 3940–3947; (b) K. Monde, N. Harada,
M. Takasugi, P. Kutschy, M. Such ´y and M. Dzurilla, J. Nat.
Prod., 2000, 63, 1312–1314.
2
1
1
34–243; (e) V. Schurig, J. Chromatogr. A, 2009, 1216, 1723–
736; (f) M. Jung and V. Schurig, J. Chromatogr., 1992, 605, 22 K. D. Klika, M. Budovsk ´a and P. Kutschy, Tetrahedron:
61–166; (g) O. Trapp and V. Schurig, Tetrahedron:
Asymmetry, 2010, 21, 647–658.
Asymmetry, 2010, 21, 1334–1340.
9 K. D. Klika, M. Budovsk ´a and P. Kutschy, J. Fluorine Chem.,
23 W. Song, Y. Zhou, Y. Fu and W. Xu, Tetrahedron: Asymmetry,
2013, 24, 909–912.
1
2010, 131, 467–476.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 2988–2993 | 2993