B(OMe)3 as a Nonacidic Iminium Ion Generator
virtually nonacidic, the present reaction system offers a new
access to amine derivatives through generation of iminium
ions under mild reaction conditions.
Acknowledgments
This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science, and Tech-
nology, Japan.
Experimental Section
[1]
[2]
[3]
a) E. D. Kleinman in Comprehensive Organic Synthesis (Eds.:
B. M. Trost), Peramon, Oxford, 1991, vol. 2. pp. 893; b) M.
Arend, B. Westermann, N. Risch, Angew. Chem. Int. Ed. 1998,
37, 1044.
General Procedure for the B(OMe)3-Mediated Mannich-Type Reac-
tion: A solution of B(OMe)3 (89 µL, 83 mg, 0.80 mmol), secondary
amine (0.40 mmol), and aldehyde (0.60 mmol) in DMSO (1.0 mL)
was stirred for 10 min at room temperature. To the solution was
added ketene silyl acetal 4 (0.60 mmol) at room temperature. The
mixture was stirred at room temperature for 5 h, quenched with ice
water, and extracted with ethyl acetate. The organic layer was
washed with water, and the aqueous layer was extracted with ethyl
acetate. The combined organic layer was dried with Na2SO4 and
filtered, and the solvents evaporated under vacuum. The crude ma-
terial was purified by silica gel column chromatography to give β-
amino esters 5. For the synthesis of 5hk and the 10 mmol-scale
reactions, the products were isolated by acid–base extraction [0.5
HCl (aq.)/28% NH3 (aq.)]. See Supporting Information for details.
a) I. Ugi, Angew. Chem. Int. Ed. Engl. 1962, 1, 8; Angew. Chem.
1962, 74, 9; b) A. Dömling, I. Ugi, Angew. Chem. Int. Ed. 2000,
39, 3198; c) M. Suginome, Y. Ito in Science of Synthesis (Eds.:
S.-I. Murahashi), Thieme, Stuttgart, 2004, vol. 19, pp. 445.
a) C. D. Bailey, C. E. Houlden, G. L. Bar, G. C. Lloyd-Jones,
K. I. Booker-Milburn, Chem. Commun. 2007, 2932; b) F. Gao,
G. Zhang, S. Zhang, Y. Cheng, Z. Shi, Y. Li, J. Gao, Tetrahe-
dron 2007, 63, 3973; c) Z. Zhou, F. Xu, X. Han, J. Zhou, Q.
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K. Fujita, D. Teraoka, Synlett 2006, 2646; g) J.-R. Ela-Menye,
W. Dobbs, M. Billet, P. Klotz, A. Mann, Tetrahedron Lett.
2005, 46, 1897.
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W. N. Speckamp, M. J. Moolenaar, Tetrahedron 2000, 56, 3817.
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ami, Org. Lett. 2004, 6, 1167.
Y. Tanaka, T. Hasui, M. Suginome, Synlett 2008, 1239.
For reviews on the boronic acid based catalysts, see: a) P. J.
Duggan, E. M. Tyndall, J. Chem. Soc. Perkin Trans. 1 2002,
1325; b) K. Ishihara in Boronic Acids (Ed.: D. G. Hall), Wiley-
VCH, Weinheim, 2005, pp. 377.
General Procedure for the B(OMe)3-Mediated Ugi-Type Reaction:
A solution of B(OMe)3 (134 µL, 125 mg, 1.2 mmol), secondary
amine (0.60 mmol), aldehyde (0.40 mmol), and isocyanide
8
(0.60 mmol) in 1,2-dichloroethane (1.0 mL) was stirred at 80 °C for
12 h. The mixture was cooled to room temperature, quenched with
ice water, and extracted with ethyl acetate. The organic layer was
washed with water, and the aqueous layer was extracted with ethyl
acetate. The combined organic layer was dried with Na2SO4 and
filtered, and the solvents evaporated under vacuum. The crude ma-
terial was purified by silica gel column chromatography to give α-
amino amides 9.
[7]
[8]
[9]
[10]
[11]
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures and characterization of the
new compounds are described.
Received: December 1, 2008
Published Online: January 28, 2009
Eur. J. Org. Chem. 2009, 1148–1151
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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