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ChemComm
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4
5
A plausible reaction mechanism is proposed in (Scheme 6) on
the basis of experimental results and literature reports.19 Firstly,
tryptoline 1 gets oxidized to 3,4-dihydro-β-carboline 5 in the
presence of IBX followed by activation of imine with second
molecule of IBX or IBA facilitating the isocyanide addition to form
the nitrilium ion B. Intermediate B might convert to the product 3
via two routes (Path a and b). As observed from the isotopic
labeling experiments, it can be postulated that addition of water to
intermediate B leads to the formation of product 3 (Path a).
Another possibility is shown in Path b, wherein the intermediate B
rearranges to D through intramolecular hydroxyl transfer leading to
the formation of product 3.
Lin, S. Khan, C. Ruiz, T. Schröter, W. Grant, A. Weiser, J.
DOI: 10.1039/C9CC05215A
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6
7
O
O
O
HO
N
N
I
-H2
O
IBX
NH O
O
O
-IBA
I
N
5
N
H
H
IBX
OH
N
1
8
9
A
N
H
R
O
O
R
HO
N
O
I
N
N
Path a
N
H
N
H
H
N
H
OH
O
N
HN
R
N
B
C
H2
O
R
3
O
O
10 H. Masui, N. Ishizawa, S. Fuse, T. Takahashi, Tetrahedron,
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82, 5285.
I
O
OH
IBA
O
HO
N
Path b
I
N
N
H
N
I
O
O
O
O
HN
N
O
N
H
HN
H
O
H
3
R
N
R
D
B
R
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Scheme 6. Proposed reaction mechanism.
In conclusion, we have developed a general method for the
efficient synthesis of imino-carboxamides from tryptoline and THIQ
moieties through isocyanide addition. This strategy features high
atom economy with broad substrate scope and operationally simple
reaction procedure. Gram scale synthesis of the alkaloids
alangiobussine and alangiobussinine were performed in single step.
Pharmaceutical properties and synthetic applications of these
imino-carboxamides are being explored and will be reported in due
course.
Conflicts of interest
There are no conflicts to declare.
Notes and references
1
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20 A probable complex of product 3a with IBA was obtained as
following structure based on NMR and Mass analysis (see
ESI):
2
3
Z. Xiao, Z. Liu, C. Lei, J. Wang, Z. Chen, G. Han, Y. Xiao, H. He,
S. Chen, CN103130800A, 2013.
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N
I
N
O
H
O
O
NH
VII
4 | J. Name., 2012, 00, 1-3
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