4428
C. O’Reilly et al. / Tetrahedron Letters 50 (2009) 4427–4429
one-pot sequence included azide incorporation, Huisgen cycload-
OH
OH
O
O
O
dition, triazoline decomposition, aziridine formation, and its
subsequent reaction with azide. The 8-oxa-3-azabicyclo[3.2.1-
]octanes are of medicinal interest. For example, achiral 8-oxa-3-
azabicyclo[3.2.1]octane12,13 has analgesic and anti-inflammatory
effects in vivo14 and analogues have been prepared.15 The pro-
tected amino acid 10 could have application in peptidomimetic
development.16 Sorbose derivative 9 can be considered a conform-
ationally constrained morpholine derivative17 and is structurally
related to bicyclic alkaloids with nortropane skeletons, which have
been found to have biological activity as glycosidase inhibitors.18
Lactam 12 contains a tricyclic framework.19 A recent analysis of
scaffolds investigated in organic chemistry showed that a small
number of frameworks are found in a large number of all known
compounds.20 The approach described herein using readily avail-
able carbohydrate precursors has potential to be applied to gener-
ating new functional frameworks for organic chemistry.
Ref. 8
46%
O
HO
O
O
OH
HO
7
6
1. SOCl2, py.
O
O
60% AcOH, 79%
HO
2. NaN3, DMF,
heat, 40% two
steps
O
HO
8
N3
N3
H
H
N
N
HCl, MeOH
60%
O
O
OH
O
O
HO
HO
OH
9
10
Scheme 2.
Acknowledgments
described in Scheme 1, where, under the reaction conditions, it was
not possible to observe the triazoline or aziridine intermediates.10
Efforts to improve the yield of 9 from the one-pot reaction were
not successful. The X-ray crystal structure of 9 (Fig. 1) confirmed
the structure of the bicyclic compound and the configuration of
the newly generated stereocenter. Removal of the isopropylidene
from 9 was effected using 0.2 M HCl in MeOH to give polyhydroxy-
lated compound 10.
The authors are grateful to the UCD NMR and MS services and to
Dr. Helge Mueller-Bunz for the X-ray crystal structure determina-
tion. The research was supported by Science Foundation Ireland
(PI/IN1/B966, 03/IBN/B352) and the Higher Education Authority’s
Programme for Research in Third Level Institutions.
Treatment of 9 with ethyl bromoacetate in THF along with a
catalytic amount of tetrabutylammonium iodide gave 11 (61%),
which can be considered to be a protected sugar amino acid.11 Cat-
alytic hydrogenation of 11 caused reduction of the azide to the
amine which led to spontaneous lactam formation; subsequent re-
moval of the acetonide from the intermediate gave tricyclic deriv-
ative 12 in 58% yield over two steps (Scheme 3).
Supplementary data
Supplementary (general experimental methods, experimental
procedures, analytical data, 1H and 13C NMR spectra, crystallo-
graphic information file for 9) data associated with this article can
In summary, iminocyclitols with an ether bridge have been pre-
References and notes
pared in a concise and stereoselective manner from L-sorbose. The
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N1
N2
C5
N3
N4
C6
O1
C3
C4
O3
C7
C8
C1
C10
C9
O4
O2
C2
Figure 1. ORTEP representation of the X-ray crystal structure of 9. The atomic
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displacement parameters are at the 50% level. CCDC 731460.
N3
O
EtO2C
H
N
N3
O
Br
CO2Et
N
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reflux, 6 h
63%
O
HO
HO
O
9. For
a review on applications of organic azides including alkene–azide
O
9
11
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Chem., Int. Ed. 2005, 44, 5188–5240.
NH
N
1. Pd-C, H2
EtOAc, 83%
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O
2.HCl-MeOH
70%
OH
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HO
OH
12
12. Neth, H.; Wiggins, L. F. J. Chem. Soc. 1948, 155–158.
Scheme 3.