organic chemicalcommunity. Cascade reactions thatallow
multiple transformations in a single-pot process are espe-
cially attractive.5 Recently, Chang, Wang, and others
made a great contribution in ketenimine chemistry, which
involves a Cu-catalyzed azideÀalkyne cycloaddition.6À8
Various heterocycles have been constructed based on this
strategy. For example, the 1,2-dihydroisoquinolin-3(4H)-
imine scaffold could be produced via a copper(I)-catalyzed
reaction of (E)-2-ethynylphenylchalcone, sulfonyl azide, and
amine.4f In the meantime, reactions of methylenecyclopro-
panes are particularly appealing due to their diverse reactivity
driven by the relief of ring strain.9Over the past decades, the
ring-opening reactions of methylenecyclopropanes to form a
variety of carbocycles and heterocycles have been extensively
explored.10À12 Prompted by the advancement of ketenimine
chemistry and the attractiveness of methylenecyclopropanes,
we envisaged that the combination might be applied to the
preparation of fused indoline derivatives based on our recent
efforts for N-heterocycles generation.
Our strategy is illustrated in Scheme 1. We reasoned that
2-ethynylaryl methylenecyclopropane 1 would react with
sulfonyl azide 2 catalyzed by a copper salt affording the
triazole intermediate a, which then transferred to the reac-
tive ketenimine b via a ring-opening rearrangement. A
consecutive 6π-electrocyclization would occur to form an
intermediate c, which subsequently underwent a rearran-
gement to produce the fused indolines 3. To demonstrate
the feasibility of this proposed synthetic route, we started
to explore the possibility of this transformation.
(8) (a) Shen, Y.; Cui, S.; Wang, J.; Chen, X.; Lu, P.; Wang, Y.-G. Adv.
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Y.; Ju, K.; He, X.; Hu, J.; Yu, S.; Zhang, M.; Liao, K.; Wang, L.; Zhang,
P. J. Org. Chem. 2010, 75, 5743. (d) Cano, I.; Alvarez, E.; Nicasio, M. C.;
ꢀ
Perez, P. J. J. Am. Chem. Soc. 2011, 133, 191. (e) Husmann, R.; Na,
Y. S.; Bolm, C.; Chang, S. Chem. Commun. 2010, 46, 5494. (f) Jin, H.;
Xu, X.; Gao, J.; Zhong, J.; Wang, Y.-G. Adv. Synth. Catal. 2010, 352,
347. (g) Song, W.; Lu, W.; Wang, J.; Lu, P.; Wang, Y.-G. J. Org. Chem.
2010, 75, 3481. (h) Lu, W.; Song, W. Z.; Hong, D.; Lu, P.; Wang, Y.-G.
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Lett. 2006, 8, 4517. (k) Xu, X.; Cheng, D.; Li, J.; Guo, H.; Yan, J. Org.
Lett. 2007, 9, 1585. (l) Whiting, M.; Fokin, V. V. Angew. Chem., Int. Ed.
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J.; Jiang, Z.; Wang, Y.-G. Synlett 2009, 2023. (q) Rostovtsev, V. V.;
Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed.
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Scheme 1. Proposed Synthetic Route for the Generation of
Fused Indoline Derivatives
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The preliminary screening was performed for the reac-
tion of 1-(cyclopropylidenemethyl)-2-ethynylbenzene 1a
with 4-methylbenzenesulfonyl azide 2a catalyzed by
copper(I) iodide (5 mol %) in the presence of triethylamine
in 1,4-dioxane at room temperature (Table 1). Gratify-
ingly, the desired product 3a was isolated in 67% yield
(Table 1, entry 1). The corresponding structure of indoline
3a was confirmed by X-ray diffraction analysis (see the
Supporting Information). With this promising result in
hand, we started to optimize the reaction conditions. Lower
yields were obtained when copper(I) bromide or copper(I)
chloride was used as a replacement (Table 1, entries 2 and 3).
Further screening of organic and inorganic bases indicated
that triethylamine was the best choice. Inferior yields were
displayed when other bases were employed in the model
reaction (Table 1, entries 4À11). No better results were
generated when the reaction occurred in other solvents
(Table 1, entries 12À15). The yield was decreased drama-
tically when the catalytic amount of copper(I) iodide was
reduced to 2 mol % (Table 1, entry 16). The result could
not be improved when the reaction was performed at 70 °C
(Table 1, entry 17).
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