ChemSusChem
10.1002/cssc.201701896
FULL PAPER
the binding pocket offered by the phosphoric acid, there appears Acknowledgements
to be some steric repulsion between the (R,R)-guest and the
phenanthrene moiety of the host. The Gibbs free energy
This work was supported financially by STW (project 11404), the
Swiss National Science Foundation (SNSF), the Netherlands
Ministry of Education, Culture and Science (Gravitation program
‒1
calculated for PA1⊃(S,S)-8 is 3.8 kJ mol lower than for
PA1⊃(R,R)-8, which is in line with experiment [that is, selective
extraction of the (S,S)-enantiomer, vide supra]. This steric
interaction is absent in the structures calculated for PA2 (see the
Supporting Information), which corroborates with the lower ee in
the extraction experiments.
no. 024.001.035).
and the Netherlands Organization for
Scientific Research (NWO-CW, Veni grant no. 722.014.006 to
S.J.W.) and they are all gratefully acknowledged. The authors
would also like to thank Kaja Sitkowska for her aid in designing
the TOC of this article.
Keywords: Enantioselective extraction • Amino alcohols •
Phosphoric acids • Chiral Resolution• Host-guest complexes
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Figure 4. DFT energy minimized structures [B3LYP/6-
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(left) and PA1⊃(R,R)-8.
In summary, we have investigated the efficiency of VAPOL- and
VANOL-based phosphoric acids as chiral hosts for the
enantioselective liquid-liquid extraction of
aminoalcohols. These previously unexplored hosts proved to be
good selectors for several 1,2-aminoalcohols, offering
a range of 1,2-
a
particular cost-efficient process for their resolution due to the
relatively easy synthetic availability of these phosphoric acids
and the high selectivity reached. In particular, (S)-VANOL PA2
allows for the resolution of phenylalaninol (7) while (S)-VAPOL
PA1 proved particularly efficient for the ELLE of trans-1-amino-
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selectivity of 7.2. DFT calculations have been used to shine light
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preference for binding of one of the enantiomers. The extraction
process proved also to be highly robust, tolerating small
variations in optimal conditions with little or no impact on its
efficiency. The U-tube experiments show the catalytic nature of
the extraction process as well as the feasibility of an efficient
back-extraction. In view of the high operational selectivity, this
process could be easily scaled up using as little as 5-6 stages.
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Experimental Section
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To a vial with a stirring bar, a solution of the racemic guest (0.4 ml, 2.0
mM) dissolved in a phosphate buffer solution (buffer strength 0.1 M,
indicated pH) was added to a solution of the host in CHCl (0.4 ml, 1.0
3
mM). After capping the vial, the mixture was cooled to the indicated
temperature and stirred at 900 rpm for 16 h. The phases were allowed to
separate over a period of 2 min. The aqueous phase was removed and
an aliquot was injected into a reverse phase HPLC for determination of
the ee, distribution and aop. All extraction experiments were carried out in
triplo and with a simultaneous blank reaction (concentration of host = 0.0
mM).
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