Communications
[3] Routes other than aza-MBH reactions have been developed to
access aza-MBH-type products with b-substituted a,b-unsatu-
rated carbonyl moieties, but there has been no report of
enantioselective versions of these reactions: a) J. L. G. Ruano,
I. Fernandez, M. P. Catalina, J. A. Hermoso, J. Sanz-Aparicio,
M. Martinez-Ripoll, J. Org. Chem. 1998, 63, 7157; b) H.-X.
Wei, J. D. Hook, K. A. Fitzgerald, G. Li, Tetrahedron: Asym-
metry 1999, 10, 661; c) B. Trost, C. K. Chung, J. Am. Chem.
Soc. 2006, 128, 10358.
Scheme 2. Determination of the absolute stereochemistry.
In summary, highly enantiomerically enriched aza-MBH-
type products with b-substituted enal moieties have been
prepared for the first time under mild conditions. Our results
support that these reactions proceed through a Mannich-type
reaction followed by isomerization of the double bond. This
type of mechanism might be favorably exploited in other
reactions involving enals and enones.
[4] a) Y.-L. Shi, Y.-M. Xu, M. Shi, Adv. Synth. Catal. 2004, 346, 1220;
b) Y.-L. Shi, M. Shi, Tetrahedron 2006, 62, 461; c) V. K. Aggarwal,
I. Emme, S. Y. Fulford, J. Org. Chem. 2003, 68, 692.
[5] a) W. Notz, F. Tanaka, S. Watanabe, N. S. Chowdari, J. M. Turner,
R. Thayumanuvan, C. F. Barbas III, J. Org. Chem. 2003, 68, 9624;
b) A. Cordova, S. Watanabe, F. Tanaka, W. Notz, C. F. Barbas III,
J. Am. Chem. Soc. 2002, 124, 1866; c) S. Watanabe, A. Cordova, F.
Tanaka, C. F. Barbas III, Org. Lett. 2002, 4, 4519.
[6] a) Whereas aza-MBH-type product 3 was generated by the
Received: September 27, 2006
Published online: January 29, 2007
À
formation of a C C bond at the a-position of aldehyde 1, for
the reaction between two molecules of 1 in the presence of
proline, the g-position of 1 reacted as a nucleophilic carbon atom
and [3+3] adducts were formed. This observation supports the
proposed formation of an enamine from 1 with proline: B.-C.
Hong, M.-F. Wu, H.-C. Tseng, J.-H. Liao, Org. Lett. 2006, 8, 2217;
b) formation of enamine intermediates of b-substituted a,b-
unsaturated aldehydes with a pyrrolidine derivative was also
suggested in a g-amination reaction: S. Bertelsen, M. Marigo, S.
Brandes, P. Diner, K. A. Jorgensen, J. Am. Chem. Soc. 2006, 128,
12973.
Keywords: aldehydes · asymmetric synthesis · enamines ·
imines · organocatalysis
.
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[8] Addition of excess imidazole resulted in a broadening of the
1H NMR signals of 9, but no broadening of the 1H NMR signals of
7 was observed with imidazole.
[9] Imidazole has been used or suggested as a nucleophile in MBH
reactions in the presence of proline: a) M. Shi, J.-K. Jiang, C.-Q.
Li, Tetrahedron Lett. 2002, 43, 127; b) S.-H. Chen, B.-C. Hong, C.-
F. Su, S. Sarshar, Tetrahedron Lett. 2005, 46, 8899.
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103, 811; b) V. K. Aggarwal, A. M. M. Castro, A. Mereu, H.
Adams, Tetrahedron Lett. 2002, 43, 1577.
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 1878 –1880