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LETTER
Wu, S.; Martinelli, M. J.; Moniz, G. A. Org. Process Res.
Dev. 2007, 11, 215.
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Lett. 2001, 11, 2863.
(5) Katagiri, T.; Takahashi, M.; Fujiwara, Y.; Ihara, H.;
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(6) Freedman, J.; Vaal, J. V.; Huber, E. W. J. Org. Chem. 1991,
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obtained but the enantiomeric excess remains very high
(99% ee). Besides, cyclic N-benzyl-b-amino alcohols un-
dergo rearrangement as (R)-N-benzyl-3-hydroxypiperi-
dine (2i) was obtained with 93% yield when treating (S)-
N-benzyl-prolinol (1i) with a catalytic amount of H2SO4
(5 mol%, THF, 180 °C, 16 h). We have to point out that
secondary N-benzyl-b-amino alcohols can also be rear-
ranged, as the treatment of 1j with H2SO4 (30 mol%, THF,
180 °C, 6 h) produced the rearranged product 2j but the
yield and the enantiomeric excess were lower (22% yield,
83% ee) than for the corresponding N,N-dibenzyl-b-
amino alcohol 1g (65%, 95% ee).
(7) McKay, C.; Wilson, R. J.; Rayner, C. M. Chem. Commun.
2004, 1080.
(8) Hook, D. F.; Gessier, F.; Noti, C.; Kast, P.; Seebach, D.
ChemBioChem 2004, 5, 691.
(9) Ye, C.; Shreeve, J. M. J. Fluorine Chem. 2004, 125, 1869.
(10) Métro, T.-X.; Appenzeller, J.; Gomez Pardo, D.; Cossy, J.
Org. Lett. 2006, 8, 3509.
We have shown that, when treated with a catalytic amount
of H2SO4, linear N,N-dibenzyl-b-amino alcohols of type
A as well as N-benzylprolinols can be rearranged to
b-amino alcohols of type B and to 3-hydroxypiperidines,
respectively, in good yields and enantioselectivities.
Secondary amines can also be rearranged with good
enantiomeric excess but in modest yield.
(11) For examples of cyclic b-amino alcohols rearrangement,
see: (a) Cossy, J.; Dumas, C.; Gomez Pardo, D. Eur. J. Org.
Chem. 1999, 1693. (b) Brandi, A.; Cicchi, S.; Paschetta, V.;
Gomez Pardo, D.; Cossy, J. Tetrahedron Lett. 2002, 43,
9357. (c) Déchamps, I.; Gomez Pardo, D.; Karoyan, P.;
Cossy, J. Synlett 2005, 1170. (d) Mena, M.; Bonjoch, J.;
Gomez Pardo, D.; Cossy, J. J. Org. Chem. 2006, 71, 5930.
(e) Roudeau, R.; Gomez Pardo, D.; Cossy, J. Tetrahedron
2006, 62, 2388; and references therein. (f) Déchamps, I.;
Gomez Pardo, D.; Cossy, J. ARKIVOC 2007, (v), 38. For
comprehensive reviews, see: (g) Cossy, J.; Gomez Pardo, D.
Chemtracts: Org. Chem. 2002, 15, 579. (h) Cossy, J.;
Gomez Pardo, D. Targets Heterocycl. Syst. 2002, 6, 1.
(12) Métro, T.-X.; Gomez Pardo, D.; Cossy, J. J. Org. Chem.
2007, 72, 6556.
Aknowledgment
Sanofi-Aventis is greatly acknowledged for financial support
(Grant to T.-X.M.).
References and Notes
(13) Typical Procedure
To a solution of b-amino alcohol 1a–j (1 mmol, 1.0 equiv)
in THF (1.5 mL) at r.t. was added H2SO4 (3 mL, 0.05 mmol,
5 mol%) and the reaction mixture was heated at 180 °C
during 2 h under microwave irradiation in a sealed tube.
After addition of an aq sat. Na2CO3 solution, the mixture was
extracted with EtOAc, dried over MgSO4, filtered, and
concentrated under reduced pressure. Purification of the
residue by flash chromatography (silica gel, n-pentane–
EtOAc) afforded the corresponding b-amino alcohol 2a–j.
(14) Picq, D.; Cottin, M.; Anker, D.; Pacheco, H. Tetrahedron
1983, 39, 1797.
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Synlett 2007, No. 18, 2888–2890 © Thieme Stuttgart · New York