Chemistry - A European Journal
10.1002/chem.201605361
FULL PAPER
reduced to imine 79 in moderate yields under neutral conditions
Rettstadt, D. Körtje, E. Hofer, J. Fohrer, and R. Reichel) for
extensive analyses.
[
80]
by using phosphorus tribromide in dry tetrahydrofuran at 0 °C.
In the last step, the vinyl iodide can be added in a 1,4-fashion to
the
α,β-unsaturated
ester
by
using
bis(1,5-
Keywords: akuammiline alkaloids • monoterpenoid indole
alkaloids • total synthesis • Stevens rearrangement • [2,3]-
sigmatropic rearrangement
cyclooctadiene)nickel(0) according to
a
literature-known
[
19]
procedure (Scheme 14).
[
[
[
[
[
[
[
[
1]
2]
3]
4]
5]
6]
7]
8]
M.-L. Bennasar, E. Zulaica, M. López, J. Bosch, Tetrahedron Lett.
988, 29, 2361–2364.
J. Lévy, J. Sapi, J.-Y. Laronze, D. Royer, L. Toupet, Synlett 1992,
, 601–602.
M.-L. Bennasar, E. Zulaica, A. Ramírez, J. Bosch, J. Org. Chem.
996, 61, 1239–1251.
M.-L. Bennasar, E. Zulaica, A. Ramírez, J. Bosch, Tetrahedron
Lett. 1996, 37, 6611–6614.
M.-L. Bennasar, E. Zulaica, A. Ramírez, J. Bosch, Tetrahedron
1
7
1
1
999, 55, 3117–3128.
Y. Yasui, T. Kinugawa, Y. Takemoto, Chem. Commun.
Cambridge, U. K.) 2009, 4275–4277.
Y. Komatsu, K. Yoshida, H. Ueda, H. Tokuyama, Tetrahedron Lett.
013, 54, 377–380.
(
2
M. Kawano, T. Kiuchi, S. Negishi, H. Tanaka, T. Hoshikawa, J.
Matsuo, H. Ishibashi, Angew. Chem., Int. Ed. Engl. 2013, 52, 906–
9
10.
M. Zhang, X. Huang, L. Shen, Y. Qin, J. Am. Chem. Soc. 2009,
31, 6013–6020.
[
9]
1
[
[
10]
11]
W. Zi, W. Xie, D. Ma, J. Am. Chem. Soc. 2012, 134, 9126–9129.
L. Zu, B. W. Boal, N. K. Garg, J. Am. Chem. Soc. 2011, 133,
Scheme 14. Final transformations to strictamine (1).
8
877–8879.
G. L. Adams, P. J. Carroll, A. B. Smith, 3rd, J. Am. Chem. Soc.
013, 135, 519–528.
[
[
[
[
[
12]
13]
14]
15]
16]
2
B. D. Horning, D. W. MacMillan, J. Am. Chem. Soc. 2013, 135,
6442–6445.
M. Teng, W. Zi, D. Ma, Angew. Chem., Int. Ed. Engl. 2014, 53,
Conclusions
1
814–1817.
We have accomplished a formal total synthesis of strictamine (1)
based on 21 isolated steps (34 chemical transformations). The
unexpected and undesired reactivities of some intermediates are
illustrated by observed side reactions. Especially challenging
was the suppression of fragmentation reactions under loss of the
established quaternary carbon center. This reaction pathway
was favored under many conditions and one of the major
drawbacks during the development of this synthetic route to
strictamine (1). We were able to show the versatility of a
Stevens [2,3]-sigmatropic rearrangement for the construction of
the 2-azabicyclo[3.3.1]nonane system 5, which represents the
key transformation in our synthesis of strictamine (1).
Furthermore, a second Stevens [2,3]-sigmatropic rearrangement
was demonstrated to be a powerful reaction to establish the
correct relative stereochemistry of the highly substituted
pyrrolidine 9.
W. Ren, Q. Wang, J. Zhu, Angew. Chem., Int. Ed. Engl. 2014, 53,
1818–1821.
J. M. Smith, J. Moreno, B. W. Boal, N. K. Garg, J. Am. Chem. Soc.
2
014, 136, 4504–4507.
M. W. Smith, S. A. Snyder, J. Am. Chem. Soc. 2013, 135, 12964–
2967.
[17]
18]
[19]
1
[
J. Moreno, E. Picazo, L. A. Morrill, J. M. Smith, N. K. Garg, J. Am.
Chem. Soc. 2016, 138, 1162–1165.
W. Ren, Q. Wang, J. Zhu, Angew. Chem., Int. Ed. Engl. 2016, 55,
3
500–3503.
[
[
[
[
20]
21]
22]
23]
D. Nishiyama, A. Ohara, H. Chiba, H. Kumagai, S. Oishi, N. Fujii,
H. Ohno, Org. Lett. 2016, 18, 1670–1673.
R. Eckermann, M. Breunig, T. Gaich, Chem. Commun. 2016, 52,
1
1363–11365.
A. R. Battersby, M. Thompson, K. H. Glüsenkamp, L.-F. Tietze,
Chem. Ber. 1981, 114, 3430–3438.
A. R. Battersby, N. D. Westcott, K. H. Glüsenkamp, L.-F. Tietze,
Chem. Ber. 1981, 114, 3439–3447.
A. I. Scott, Acc. Chem. Res. 1970, 3, 151–157.
J. Stockigt, L. Barleben, S. Panjikar, E. A. Loris, Plant Physiol.
Biochem. 2008, 46, 340–355.
E. Wenkert, J. Am. Chem. Soc. 1962, 84, 98–102.
R. Eckermann, T. Gaich, Chem. Eur. J. 2016, 22, 5749–5755.
E. Wenkert, B. Wickberg, J. Am. Chem. Soc. 1965, 87, 1580–
[24]
[
25]
[
[
[
26]
27]
28]
1
589.
Experimental Section
[29]
A.-u.-. Rahman, A. Basha, Biosynthesis of Indole Alkaloids,
Clarendon Press, Oxford, 1983.
[
[
30]
31]
R. Eckermann, T. Gaich, Synthesis 2013, 45, 2813–2823.
J. M. Smith, J. Moreno, B. W. Boal, N. K. Garg, Angew. Chem., Int.
Ed. Engl. 2015, 54, 400–412.
H. K. Schnoes, K. Biemann, J. Mokry, I. Kompis, A. Chatterjee, G.
Ganguli, J. Org. Chem. 1966, 31, 1641–1642.
Experimental and crystallographic details as well as compound
1
13
characterization data and copies of
available in the Supporting Information.
H
and
C NMR spectra are
[
[
32]
33]
Y. Hou, X. Cao, L. Wang, B. Cheng, L. Dong, X. Luo, G. Bai, W.
Gao, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 2012,
9
08, 98–104.
J. A. Vanecko, H. Wan, F. G. West, Tetrahedron 2006, 62, 1043–
062.
Acknowledgements
[
[
34]
35]
1
J. S. Clark, P. B. Hodgson, M. D. Goldsmith, L. J. Street, J. Chem.
Soc., Perkin Trans. 1 2001, 3312–3324.
J. S. Clark, P. B. Hodgson, M. D. Goldsmith, A. J. Blake, P. A.
Cooke, L. J. Street, J. Chem. Soc., Perkin Trans. 1 2001, 3325–
Financial support was granted by the Fonds der Chemischen
Industrie via Liebigstipendium and the Alexander von
a
[36]
[37]
Humboldt Foundation by the Sofja Kovalevskaja prize. We thank
the NMR and mass spectrometry departments of the Institute of
Organic Chemistry of the Leibniz University of Hannover (M.
3
337.
T. S. Stevens, E. M. Creighton, A. B. Gordon, M. MacNicol, J.
Chem. Soc. 1928, 3193–3197.
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