M. S. M. Timmer et al. / Tetrahedron Letters 52 (2011) 4803–4805
4805
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outcome of the reaction. Here it was observed that increasing the
reaction temperature (50 °C) and employing a large excess of io-
dine (repeated additions) gave the optimal yield of the desired iso-
mer 4a (3:1:1 ratio of 4a:4b:4c). From this mixture, 4b was readily
isolated via column chromatography (1% methanol in ethyl ace-
tate), but unfortunately separation of 4a and 4c proved futile.
Removal of the carbamate functionality via hydrolysis and column
chromatography, however, allowed for the isolation of DGJ (3) in
40% overall yield from 5. Spectral data of 3 matched of that previ-
ously reported.17
In summary, we have presented the first example of an iodine-
mediated carbamate annulation being used for the preparation of
piperidines. This reaction is even more important given the pro-
pensity of the annulation to favour the formation of six- versus
five-membered rings. The applicability of this methodology offers
many new opportunities in the synthesis of natural products and
other synthetic targets, as illustrated by our remarkably efficient
strategy for the synthesis of DGJ – the shortest route to date.
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Acknowledgements
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N.; Kibayashi, C. J. Org. Chem. 1991, 56, 815; (b) Liu, K. K.-C.; Kajimoto, T.; Chen,
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The authors would like to thank Industrial ResearchLtd Capabil-
ity Fund (S.A.G.) and Victoria University of Wellington (Early Ca-
reer Research Excellence Award, M.S.M.T.).
Supplementary data
Supplementary data associated with this article can be found, in
10. Dangerfield, E. M.; Plunkett, C. H.; Win-Mason, A. L.; Stocker, B. L.; Timmer, M.
S. M. J. Org. Chem. 2010, 75, 5470–5477.
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