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Journal Name
COMMUNICATION
Scheme 3. A plausible mechanism
DOI: 10.1039/C8CC04264K
We tested the reaction on one internal ynamide 1s that
reacted with benzisoxazole 2a, in the presence of gold catalyst,
to from compound 5m’ in 59% yield; this information confirms
the intermediacy of gold carbene intermediates (eq 4). To
expand the reaction scope, we examined such cascade
forming indoles that attack again at the benzaldehyde. This
high-temperature effect avoids the formation of 2-amino-7-
formylindoles from the Hashmi’s reaction.3a The utility of this
method is manifested by a satisfactory range of N-aryl
ynamides and benzisoxazoles. Our preliminary results indicate
that a phenoxyethyne is also a applicable substrate. To
manifest the utility of this new method, we have completed
the formal synthesis of three naturally occurring alkaloids
based on this new catalysis.
annulations on phenoxyalkyne 6 8a
,
which reacted with
benzisoxazole 2a under standard conditions to yield distinct
heterocyclic compound in 42% yield (eq 5).
7
Indoloquinoline 5d undergoes a facile deprotection to
remove the mesyl group, producing 8d in 76% yield (eq 6).
Compound 5d was treated with Cs2CO3 in THF/MeOH (1:1)
under reflux in 27 h, from which we obtained compound 8d in
76% yield. In the literature,5a-5b,9 compound VI-1 and its methy
derivative, neocryptolepine VI-2 were prepared smoothly from
our resulting indolo[2,3-b]quinoline 3o (eq 7). We launched a
formal synthesis of the third target, methylneocryptolepine VI-
Conflicts of interest
There are no conflicts to declare.
3
based on our new method. To our pleasure, gold-catalyzed
reactions of 3-methylbenzisoxazole 2l with ynamide 1o in hot
DCE (70 °C , 1 h) afforded desired 8a in 34% yield, which was
convertible to the key intermediate 8b before preceeding to
the desired alkaloid VI-3 (eq 8)10.
Acknowledgements
We thank the Ministry of Education (MOE 106N506CE1) and
Ministry of Science and Technology (MOST 107-3017-F-007-
002), Taiwan, for financial support of this work.
Notes and references
1
(a) D. B. Huple, S. Ghorpade and R.-S. Liu, Adv. Synth. Catal.,
2016, 358, 1348; (b) L. Li, T.-D. Tan, Y.-Q. Zhang, X. Liu and L.-
W. Ye, Org. Biomol. Chem., 2017, 15, 8483.
2
(a) A.-H. Zhou, Q. He, C. Shu, Y.-F. Yu, S. Liu, T. Zhao, W.
Zhang, X. Lu and L.-W. Ye, Chem. Sci., 2015, 6, 1265; (b) X.-Y.
Xiao, A.-H. Zhou, C. Shu, F. Pan, T. Li and L.-W. Ye, Chem.
Asian J., 2015, 10, 1854; (c) W.-B. Shen, X.-Y. Xiao, Q. Sun, B.
Zhou, X.-Q. Zhu, J.-Z. Yan, X. Lu and L.-W. Ye, Angew. Chem.
Int. Ed., 2017, 56, 605; (d) S. S. Giri and R.-S. Liu, Chem. Sci.,
Scheme 3 shows a proposed mechanism of this gold
2018,
9
, 2991; (e) B. D. Mokar, P. D. Jadhav, Y. B. Pandit and
, 4488.
catalysis. An initial N-attack3 of benzisoxazoles 2a at
π-alkyne
R.-S. Liu, Chem. Sci., 2018,
9
complexes 1a yielded alkenylgold species I-1
, further
3
(a) H. Jin, L. Huang, J. Xie, M. Rudolph, F. Rominger and A. S.
K. Hashmi, Angew. Chem. Int. Ed., 2016, 55, 794; (b) H. Jin, B.
Tian, X. Song, J. Xie, M. Rudolph, F. Rominger and A. S. K.
Hashmi, Angew. Chem. Int. Ed., 2016, 55, 12688.
producing gold carbenes I-2 via a cleavage of the N-O bond. At
high temperatures, the N-aryl nucleophile is conformational
flexible to attack gold carbenes I-2 preferably, generating
reactive indole species I-3. An addition of this indole at the
benzaldehyde is expected to yield azacyclic product 3a via
4
5
6
(a) R. L. Sahani and R.-S. Liu, Angew. Chem. Int. Ed., 2017, 56,
1026; (b) R. L. Sahani and R.-S. Liu, Angew. Chem. Int. Ed.,
2017, 56, 12736.
dehydration of species I-4
.
(a) H. K. Kadam and S. G. J. Tilve, Heterocyclic Chem., 2016,
53, 2066; (b) P. T. Parvatkar, P. S. Parameswaran and S. G.
Tilve, Curr. Org. Chem., 2011, 15, 1036.
(a) G. V. Subbaraju, J. Kavitha, D. Rajasekhar and I. J. Jimenez,
J. Nat. Prod., 2004, 67, 461; (b) K. Cimanga, T. D. Bruyne, L.
Pieters and A. J. Vlietinck, J. Nat. Prod., 1997, 60, 688; (c) S. V.
Miert, S. Hostyn, B. U. W. Maes, K. Cimanga, R. Brun, M.
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and L. J. Pieters, Nat. Prod., 2005, 68, 674; (d) P.-C. Wanda, F.
In summary, we have designed a new path for the gold-
catalyzed annulations11 of N-aryl ynamides12-13 with
benzisoxazoles to construct 6H-indolo[2,3-b]quinoline
frameworks. Besides the electron-rich property of N-aryl group,
the success of these reactions relies on the operations at high
temperatures to enable a N-aryl group to attack gold carbenes,
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