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Scheme 2
generated in situ to afford the N-acyliminium ion intermediate
(B) which then affords the final products via a stereoselective
Pictet–Spengler reaction by attack of the aromatic ring onto the
Re face of the N-acyliminium ion (pathway 1).3d,4b 2. At 180 °C
for 2 minutes, the condensation of (L)-tryptophanol and ketocar-
boxylic acid generates the bicyclic lactam intermediate (C) via a
stereoselective Meyers’ reaction. This bicyclic lactam could be
converted, under microwave conditions, into intermediate (B),
which then affords the final products via a stereoselective Pictet–
Spengler reaction (pathway 2)3b,11 (Scheme 2). It should be
noted that, to date, the intermediates (A) and (B) have not been
observed by us. However, under microwave conditions we were
able to isolate the intermediate (C) in some cases by performing
the reaction at 110 °C for 10 minutes. This result may support
the second hypothesis.
In summary, we have described an environment-friendly
efficient method for the racemic and asymmetric diastereoselec-
tive preparation of indole alkaloids using a microwave-assisted
Pictet–Spengler reaction of tryptamine or tryptophanol deriva-
tives with ketocarboxylic acids under solvent- and catalyst-free
conditions. Desired products were obtained in short reaction
times and were isolated with high yields after simple extraction
or by precipitation in methanol.
Acknowledgements
We are grateful to the institutions that support our laboratory
(Inserm, Université de Lille2, Institut Pasteur de Lille, USTL).
10 For selected examples, see: (a) M. Jida, R. Deprez-Poulain, S. Malaquin,
P. Roussel, F. Agboussou-Niedercorn, B. Deprez and G. Laconde, Green
Chem., 2010, 12, 961; (b) M. Jida, S. Malaquin, R. Deprez-Poulain,
G. Laconde and B. Deprez, Tetrahedron Lett., 2010, 51, 5109.
Notes and references
1 For selected reviews and examples, see: (a) R. J. Sundberg, The Chem-
istry of Indoles, Academic Press, New York, 1970; (b) J. A. Joule, Indole
11 S. M. Allin, S. L. James, W. P. Martin, T. A. D. Smith and
M. R. J. Elsegood, J. Chem. Soc., Perkin Trans. 1, 2001, 3029.
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