Angewandte
Chemie
subjected to hydride transfer to give the desired tetrahydro-
quinoline 3. Subsequent proton transfer will then recycle the
Brønsted acid 1 and generate a second equivalent of the
Hantzsch pyridine.
In summary, we have developed a Brønsted acid catalyzed
cascade transfer hydrogenation, which provides direct access
to a variety of 2-aryl- and 2-alkyl-substituted tetrahydroqui-
nolines with excellent enantioselectivities and good yields.
The mild reaction conditions of this metal-free reduction of
heteroaromatic compounds, the operational simplicity and
practicability, as well as the low catalyst loading render this
transformation an attractive approach to optically active
tetrahydroquinolines and their derivatives. Further work will
be directed toward the application of this enantioselective
Brønsted acid catalyzed transfer hydrogenation to multi-
substituted quinolines and other heteroaromatic systems.
Received: January 17, 2006
Published online: April 26, 2006
Figure 1. Proposed transition structure derived from an X-ray crystal
structure of chiral Brønsted acid 1 f and 2-methylquinoline.
Keywords: asymmetric hydrogenation · Brønsted acid ·
.
Hantzsch dihydropyridine · organocatalysis ·
tetrahydroquinoline
[
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[4]For a comprehensive review on 1,2,3,4-tetrahydroquinolines,
Scheme 1. Proposed mechanism for the Brønsted acid catalyzed
cascade transfer hydrogenation.
see: A. R. Katritzky, S. Rachwal, B. Rachwal Tetrahedron 1996,
5
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[
2
of the first hydride from the dihydropyridine 4 generates the
enamine 5 and pyridinium salt B, which undergoes proton
transfer to regenerate the Brønsted acid 1 and Hantzsch
pyridine 6. The enamine 5 reacts in a second cycle with
Brønsted acid 1 to produce iminium C, which will again be
M. Bolte, Org. Lett. 2005, 7, 3781; for a subsequent optimization
of this prodedure, see: c) S. Hofmann, A. M. Seayad, B. List,
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Angew. Chem. Int. Ed. 2006, 45, 3683 –3686
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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