P. S. Schulz et al. / Tetrahedron: Asymmetry 20 (2009) 2479–2481
2481
the split diminishes again. This behavior was interpreted as the
Acknowledgments
subsequent aggregation of isolated ions to contact ion pairs and
then to quadruples and/or higher aggregates. Efficient peak split-
ting was attributed to ion pair formation. We have now demon-
strated that this is not necessarily the case. Obviously, in a
contact ion pair of 1 the diastereomeric interaction is not strong
enough to allow differentiation by NMR spectroscopy between
the (R,S)(R)- and the (R,S)(S)-diastereomer. We suggest that a dis-
tinct arrangement of cation to anion is necessary to allow strong
interaction. In the case of 1 this arrangement is enabled only in
the aggregates.
The authors wish to thank the German Science Foundation
(DFG) for funding this work within its priority program 1191 ‘Ionic
Liquids’.
References
1. Berthod, A.; He, L.; Armstrong, D. W. Chromatographia 2001, 53, 63–68.
2. Ding, J.; Welton, T.; Armstrong, D. W. Anal. Chem. 2004, 76, 6819–6822.
3. Rizvi, S. A. A.; Shamsi, S. A. Anal. Chem. 2006, 78, 7061–7069.
ˇ
´
ˇ
4. Maier, V.; Horáková, J.; Petr, J.; Drahonovsky, D.; Ševcík, J. J. Chromatogr., A
2006, 1103, 337–343.
5. François, Y.; Varenne, A.; Juillerat, E.; Villemin, D.; Gareil, P. J. Chromatogr., A
2007, 1155, 134–141.
3. Conclusion
6. Tran, C. D.; Mejac, I. J. Chromatogr., A 2008, 1204, 204–209.
7. Howarth, J.; Hanlon, K.; Fayne, D.; McCormac, P. Tetrahedron Lett. 1997, 38,
3097–3100.
8. Earle, M. J.; McCormac, P. B.; Seddon, K. R. Green Chem. 1999, 1, 23.
9. Doherty, S.; Goodrich, P.; Hardacre, C.; Knoght, J. G.; Nguyen, M. T.; Pârvulescu,
V. I.; Paun, C. Adv. Synth. Catal. 2007, 349, 951–963.
10. Gausepohl, R.; Buskens, P.; Kleinen, J.; Bruckmann, A.; Lehmann, C. W.;
Klankermeyer, J.; Leitner, W. Angew. Chem., Int. Ed. 2006, 45, 3689–3692.
11. Pégot, B.; Vo-Thanh, G.; Loupy, A. Tetrahedron Lett. 2004, 45, 6425–6428.
12. Garre, S.; Parker, E.; Ni, B.; Headley, A. D. Org. Biomol. Chem. 2008, 6, 3041–
3043.
13. Zhang, Q.; Ni, B.; Headley, A. D. Tetrahedron 2008, 64, 5091–5097.
14. Schmitkamp, M.; Chen, D.; Leitner, W.; Klankermeyer, J.; Franciò, G. Chem.
Commun. 2007, 4012–4014.
15. Schulz, P. S.; Müller, N.; Bösmann, A.; Wasserscheid, P. Angew. Chem., Int. Ed.
2007, 46, 1293–1295.
16. Schneiders, K.; Bösmann, A.; Schulz, P. S.; Wasserscheid, P. Adv. Synth. Catal.
2009, 351, 432–440.
17. Luo, S.; Mi, X.; Zhang, L.; Liu, S.; Xu, H.; Cheng, J.-P. Angew. Chem., Int. Ed. 2006,
45, 3093–3097.
18. Luo, S.; Zhang, L.; Mi, X.; Qiou, Y.; Cheng, J.-P. J. Org. Chem. 2007, 72, 9350–
9352.
19. Ni, B.; Zhang, Q.; Headley, A. D. Tetrahedron Lett. 2008, 49, 1249–1252.
20. Hayamizu, K.; Aihara, Y.; Arai, S.; Garcia Martinez, C. J. Phys. Chem. B 1999, 103,
519.
21. Noda, A.; Hayamizu, K.; Watanabe, M. J. Phys. Chem. B 2001, 105, 4603.
22. Giernoth, R.; Bankmann, D. Eur. J. Org. Chem. 2005, 4529.
23. Nama, D.; Kumar, P. G. A.; Pregosin, P. S.; Geldbach, T. J.; Dyson, P. J. Inorg. Chim.
Acta 2006, 359, 1907.
24. Saito, Y.; Umecky, T.; Niwa, J.; Sakai, T.; Maeda, S. J. Phys. Chem. B 2007, 11794.
25. Annat, G.; MacFarlane, D. F.; Forsyth, M. J. Phys. Chem. B 2007, 9018.
26. Gierer, A.; Wirtz, K. Z. Naturforsch., A 1953, 8, 522.
27. Spernol, A.; Wirtz, K. Z. Naturforsch., A 1953, 8, 532.
28. Zuccaccia, D.; Macchioni, A. Organometallics 2005, 24, 3476–3486.
29. Wasserscheid, P.; Bösmann, A.; Bolm, C. Chem. Commun. 2002, 201–202.
30. Kumar, V.; Pei, C.; Olsen, C. E.; Schäffer, S. J. C.; Parmar, V. S.; Malhotra, S. V.
Tetrahedron: Asymmetry 2008, 19, 664–671.
Our work demonstrates that the concentration range that al-
lows effective chirality transfer in synthetic applications can be
rationalized by NMR spectroscopy. We anticipate that by using
the herein described technique it will be possible to predict for a
given reaction of a prochiral ion in a chiral ionic liquid the suitable
concentration range for potential chirality transfer.
4. Experimental
NMR experiments were carried out with a Jeol ECX 400 MHz
spectrometer with a 2-chanel (HF, LF)-probe. Spectra were refer-
enced to the solvent. The optical rotations were recorded with a
Polartronic E, Schmidt + Haensch.
(1R,2S)-Ephedrinium (RS)-methoxytrifluoromethylphenyl-ace-
tate 1 was synthesized by adding equimolar amounts of (RS)-meth-
oxytrifluoromethylphenylacetic
acid
to
(1R,2S)-ephedrine
dissolved in dichloromethane. After stirring for 1 h the solvent
was removed in vacuo and the product was obtained as white solid
in quantitative yield. ½a D20
ꢁ
¼ þ0:4 (c 1.0, CH2Cl2). 1H NMR (CDCl3,
400 MHz, ppm): d = 0.94 (d, 3H, CH–CH3, 3-H, 3J = 6.8 Hz), 2.44 (s,
3H, OCH3), 2.99 (dq, 1H, CH–CH3, 3J = 1.7 Hz, 3J = 6.8 Hz), 3.51 (d,
3H, N–CH3, 3J = 7.0 Hz), 5.28 (d, 1H, CH–OH, 3J = 1.7 Hz), 7.23–
7.33 (m, 8H, Phenyl-H), 7.62–7.67 (m, 2H, Phenyl-H).
13C NMR (CDCl3, 100.4 MHz, ppm): d = 8.80 (d, CH–CH3), 30.89
(d, OCH3), 55.04 (d, N–CH3), 61.63 (d, CH–CH3), 70.24 (d, CH–OH),
85.36 (u, quart., CF3–C, 3J = 26 Hz), 124.63 (CF3, 1J = 287 Hz),
125.74 (d, Phenyl-C), 127.57, 127.73, 127.79 (d, Phenyl-C), 128.20
(d, Phenyl-C), 128.43 (d, Phenyl-C), 128.91 (d, Phenyl-C), 135.26 (u,
CF3–C–C), 139.84 (u, CH–C), 171.79 (u, CO). 19F NMR (CDCl3,
376.3 MHz, ppm): d = ꢀ69.78 (CF3). Anal. Calcd for C20H24F3NO4: C,
60.14; H, 6.06; F, 14.27; N, 3.51; O, 16.02. Found: C, 60.11; H,
6.14; N, 3.40.
ˇ ˇ
31. Navrátilová, H.; de Gelder, R.; Kríz, Z. J. Chem. Soc., Perkin Trans. 2 2002, 2093–
2099.
32. Villani, F. J.; Costanzo, M. J.; Inners, R. R.; Mutter, M. S.; McClure, D. E. J. Org.
Chem. 1986, 51, 3715–3718.
33. Buckson, R. L.; Smith, S. G. J. Phys. Chem. 1964, 68, 1875–1878.
The 13C-signal for CF3-moiety is not detectable with standard techniques using
1000 scans. It was detected by using a HF-HETCOR-experiment and an experiment
with 10,000 scans using Fe(acac)3 as a relaxation agent.