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Organic & Biomolecular Chemistry
Page 4 of 6
ARTICLE
Journal Name
DOI: 10.1039/C9OB01880H
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Scheme 5 Preliminary Mechanistic Elucidation.
Conclusions
In conclusion, we have described here a series of operationally
simple, modular synthetic sequences to piperidine derivatives
from readily available Nazarov reagents and Schiff bases. The
scope and utility of this aza-annulation reaction, rooted in the
original report by Hohenlohe-Oehringen, were significantly
broadened and a protocol was developed to transform the
initial cyclization products to stable enol acetate derivatives.
The utility of the formal imino Diels-Alder reaction was
illustrated through a concise synthesis of (±)-tetrabenazine,
which proceeded in 37% overall yield from inexpensive
starting materials. Preliminary investigations on the order of
the bond-forming events suggests an aza-Michael addition,
facilitated by hydrogen bond activation, as the first elementary
reaction step. This mechanistic foundation may help to guide
the development of the asymmetric version of this reaction,
potentially mediated by chiral hydrogen bond donor or
Brønsted acid catalysts.
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Financial support from the National Science Foundation (NSF-
1566402) and the Ministry of Science and Technology in
8. K. Hohenlohe-Oehringen, Monatsh. Chem., 1962, 93, 576-581.
Taiwan
(MOST108-2636-M-009-003)
is
gratefully
acknowledged.
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Synthesis, 1987, 314-317.
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Conflicts of interest
There are no conflicts to declare.
Acknowledgements
The acknowledgements come at the end of an article after the
conclusions and before the notes and references.
11. Dichloromethane-d2, benzene-d6, acetonitrile-d3 and methanol-d4
were surveyed.
12. The use of N-tosyl dihydro-β-carboline for such reactions has been
reported by Itoh and coworkers. See, Ref. 10c.
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Notes and references
14. J. Cui, D. I. Chai, C. Miller, J. Hao, C. Thomas, J. Wang, K. A. Scheidt
4 | J. Name., 2012, 00, 1-3
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