Organic Letters
Letter
Scheme 3. Control Experiments and Proposal of the
Reaction Mechanism
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We are grateful to the National Natural Science Foundation of
China (Grant Nos. 21472056, 21602070, and 21772051) and
the Fundamental Research Funds for the Central Universities
(CCNU15ZX002 and CCNU16A05002) for financial support.
This work was also supported by the 111 Project B17019.
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However, no reaction was observed when compounds 6 and 1a
were used as substrates (Scheme 3c). Based on these results,
we proposed a possible reaction mechanism (Scheme 3d): the
reaction of compound 1a with 2a first afforded the acylation
intermediate 4, which was trapped by triethoxymethane to
afford the cyclic intermediate 7. The compound 7 then
underwent elimination reaction to afford the imide inter-
mediate 8, which further underwent Pictet−Spengler reaction
to afford the evodiamine product.
In summary, we have developed the first one-pot total
synthetic method for preparation of evodiamine and its
analogues through a continuous biscyclization reaction. A
library of polycyclic indole scaffolds bearing various sub-
stituents have been easily produced efficiently. Compared with
the traditional stepwise synthetic methods, this multicompo-
nent reaction holds the advantages of pot economy and
material availability, which offers a new strategy for the
preparation of the corresponding alkaloid derivatives. How-
ever, due to the limitations of the reaction, a few of products
are moderate to low yield. There is space to improve the yield
for one-pot total synthesis of natural products.
ASSOCIATED CONTENT
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S
* Supporting Information
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The Supporting Information is available free of charge on the
Experimental procedures, product characterizations,
1
crystallographic data, and copies of the H and 13C
Accession Codes
CCDC 1856975 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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