R. Riguera et al.
FULL PAPERS
(1m), water, saturated NaHCO3, and water, then dried (anhydrous
Na2SO4) and concentrated under reduced pressure to obtain the bis-MPA
derivative. Final purification was achieved by flash column chromatogra-
phy on silica gel (230–400 mesh, elution with hexane/ethyl acetate mix-
tures, 90–95% yields after purification). All compounds were character-
ized by optical rotation, NMR (1D, 2D) spectroscopy, HRMS (EI), and
elemental analysis.
Soc. 2003, 125, 14379–14393; g) W. R. Hoffmann, U. Weidmann,
[6] a) E. Lallana, F. Freire, J. M. Seco, E. QuiÇoꢀ, R. Riguera, Org.
guera, Chem. Eur. J. 2009, 15, 11963–11975.
[7] V. Leiro, F. Freire, E. QuiÇoꢀ, R. Riguera, Chem. Commun. 2005,
44, 5554–5556.
[8] Secondary/primary and primary/secondary (sec/prim and prim/sec)
apply only to the carbon atoms to which the amino/hydroxy groups
are linked. Sphingosines and epinephrines (adrenalines) are exam-
ples of compounds of biological interest that bear these substruc-
tures.
Acknowledgements
We thank the Ministerio de Ciencia e Innovaciꢅn (CTQ2009-08632/BQU,
CTQ2008-01110/BQU)
and
Xunta
de
Galicia
(PGIDIT06P-
[9] Two approaches that do not make any use of DdRS from the sub-
strate and are based on the cross-interaction between auxiliaries—
just DdRS from the methoxy and methine groups of the MPAs—have
been published recently. The method now described in this article is
appropriate in cases in which the application of those previous ap-
proaches presents difficulties—that is, presence of extra methoxy
groups in the substrate or overlapped methine signals—and is useful
to double-check the configurational assignment. a) V. Leiro, J. M.
XIB209029PR, PGIDIT09CSA029209PR) for financial support. V.L.
thanks the MEC for a predoctoral FPU fellowship. We are also grateful
to the Centro de Supercomputaciꢅn de Galicia for their assistance with
the computational work, to Yamakawa Chemical Industry Co. Ltd.
(Japan) for their gift of (R)- and (S)-MPA, and to Bruker EspaÇola S.A.
for its contribution as Observant Development Entity (EPO).
2143–2147; c) B. M. Trost, J. L. Belletire, S. Godleski, P. G. McDou-
[10] This approach avoids the use of protecting groups for the terminal
primary group, thus making the experimental procedure much sim-
pler.
[11] See the Supporting Information for a full explanation of the confor-
mational equilibria that justifies the DdRS signs in prim/sec benzylic
amino alcohols.
[12] The gt conformer is defined as the one in which the benzoate is
gauche to the benzamide and trans to the Me (sec/prim), or the ben-
zamide is gauche to the benzoate and trans to the Me (prim/sec).
[13] J. Lindberg, S. C. Svensson, P. Phalsson, P. Konradsson, Tetrahedron
[15] Gaussian 03, revision E.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel,
G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr.,
T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J.
Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega,
G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R.
Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao,
H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross,
C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev,
A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K.
Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakr-
zewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K.
Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz,
Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G.
Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox,
T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challa-
combe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonza-
lez, J. A. Pople, Gaussian, Inc., Wallingford, CT, 2004.
240–242; b) I. Ohtani, T. Kusumi, Y. Kashman, H. Kakisawa, J. Am.
of Chiral Compounds Using NMR Spectroscopy, Wiley, NJ, 2007;
Chemistry, Vol. 1 (Eds.: G. Helmchen, R. W. Hoffmann, J. Mulzer,
E. Schaumann), Thieme, Stuttgart, New York, 1996, p. 253; g) E. L.
Eliel, S. H. Wilen, L. N. Mander, Stereochemistry of Organic Com-
pounds, Wiley-Interscience, New York, 1994, p. 221.
[4] a) R. T. Williamson, A. Boulanger, A. Vulpanovici, M. A. Roberts,
120, 877–882; c) R. Garcꢁa, J. M. Seco, S. A. Vꢀzquez, E. QuiÇoꢀ,
R. Riguera, J. Org. Chem. 2006, 71, 1119–1130; d) Y. Yang, M. M.
Seco, S. A. Vꢀzquez, E. QuiÇoꢀ, R. Riguera, J. Org. Chem. 2002, 67,
4579–4589; f) J. M. Seco, L. H. Tseng, M. Godejohann, E. QuiÇoꢀ,
Lꢅpez, E. QuiÇoꢀ, R. Riguera, J. Am. Chem. Soc. 1999, 121, 9724–
9725.
[5] a) F. Freire, F. Calderꢅn, J. M. Seco, A. Fernꢀndez-Mayoralas, E.
ences therein. For others approaches for diols and polyols, see: b) S.
4719–4722; f) Y. Kobayashi, N. Hayashi, Y. Kishi, J. Am. Chem.
[16] In this case, the lowest-energy conformer arises from a I conforma-
À
À
tion for the C1’ N bond combined with a gg conformer for the C1’
C2’ bond.
Received: March 26, 2010
Published online: July 2, 2010
2112
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Chem. Asian J. 2010, 5, 2106 – 2112