ChemComm
Communication
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Scheme 2 Amine as an alkyne source.
´
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of a tosyl protected indole did not affect the nucleophilicity of
the ring and 6i was obtained in 73% yield.
3 For gold catalysis, see (a) C. Ferrer and A. M. Echavarren, Angew.
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The same Ugi-adducts 5b–j were subjected to endo-dig
cyclization by reaction with cationic gold. Pleasingly, most of
the reactions proceeded well and the corresponding azocinoin-
dolones 7 were isolated in good yields (Table 2). Upon using an
aliphatic amine or a phenyl substituted alkyne only 40% and
44%, respectively, of the endo-dig cyclized product was observed
(Table 2, 7f and 7h). Also with terminal acetylene only a
moderate yield of 40% was obtained (Table 2, 7g). Surprisingly,
in contrast to the exo-dig cyclization (6i), a tosyl protected
indole did not undergo endo-dig cyclization.
To further demonstrate the synthetic utility of the developed
methodology, propargyl amine was used as the alkyne source for
the synthesis of Ugi-adduct 5k. When it was subjected to intra-
molecular hydroarylation employing In(OTf)3 in the presence of
TFA as a co-catalyst and Ipr(Au)NTf2, exclusive formation of the exo-
dig cycloisomerized product 6k was observed in 62% and 70% yield
respectively (Scheme 2).
In conclusion we have developed an efficient post-Ugi regio-
selective intramolecular hydroarylation approach for the synthesis of
azepinoindolones and azocinoindolones. Employing indium(III)- or
gold(I)-catalysis, the ring closure can be directed towards an exo-dig
or endo-dig cyclization, respectively, resulting in the formation of a
7- and 8-membered ring in compounds 6 and 7. A wide range of
functional groups, introduced during the Ugi reaction, is tolerated.
The authors wish to thank the FWO [Fund for Scientific
Research – Flanders (Belgium)] and the Research Fund of the
University of Leuven (KU Leuven) for financial support. A. K. is
thankful to EMA2experts (Erasmus Mundus Action 2, Lot 11
Asia: Experts) for providing a doctoral exchange scholarship
and Z. L. is thankful to the CSC (China Scholarship Council) for
providing a doctoral scholarship.
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c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 6803--6805 6805