Organic Letters
Letter
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were also tested under the optimized conditions, and no cyclized
products were formed even after 24 h (Scheme 5, eqs 4 and 5).
Thus, the position of the tethered nucleophile in the alkyne
chain is pivotal to trigger the cascade. Although the proposed
mechanism is convincing and supported by the control
experiments, the intramolecular nucleopalladation-initiated
mechanism involving a dihydropyrrole/dihydrofuran intermedi-
ate cannot be completely ruled out (see the SI for a detailed
mechanism).
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(4) For a comprehensive review on palladium(II)-catalyzed alkene
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The formation of spiroketal 9 could be explained through a
dihydrofuran intermediate generated via palladium-catalyzed
nucleopalladation followed by protonation steps (SI). Although
one of the diastereomeric spiroketals 9a was isolated and
characterized, the second diastereomer was inseparable in pure
form.
In conclusion, we have developed a highly efficient palladium-
catalyzed domino sequence equivalent to the regioselective
hydration of alkynes followed by intramolecular Michael
addition for the synthesis of 2,3-dihydro-1H-inden-1-ones
under mild conditions. Mechanistic studies revealed that the
assistance of the tethered nucleophiles (NHTs and OH) is
essential to trigger the hydration−olefin insertion cascade to
afford the target compounds in excellent yields. Furthermore,
the reaction was found to be highly diastereoselective, furnishing
only the cis diastereomer.
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ASSOCIATED CONTENT
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S
* Supporting Information
The Supporting Information is available free of charge on the
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V.; Negi, A. S.; Khanuja, S. P. Bioorg. Med. Chem. Lett. 2008, 18, 3914−
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(13) Oliverio, M.; Nardi, M.; Costanzo, P.; Cariati, L.; Cravotto, G.;
Experimental procedures, detailed optimization, charac-
1
terization data, alternative mechanism, and H and 13C
AUTHOR INFORMATION
■
Corresponding Author
̀
Giofre, S. V.; Procopio, A. Molecules 2014, 19, 5599−5610 and
references cited therein.
Notes
The authors declare no competing financial interest.
(14) For selected examples of the synthesis of 2,3-dihydro-1H-inden-
1-ones and related compounds, see: (a) Yang, W.; Sun, X.; Yu, W.; Rai,
R.; Deschamps, J. R.; Mitchell, L. A.; Jiang, C.; MacKerell, A. D., Jr.; Xue,
F. Org. Lett. 2015, 17, 3070−3073. (b) Butkevich, A. N.; Ranieri, B.;
Meerpoel, L.; Stansfield, I.; Angibaud, P.; Corbu, A.; Cossy, J. Org.
Biomol. Chem. 2014, 12, 728−731. (c) Feng, J.; Lu, G.; Lv, M.; Cai, C. J.
Org. Chem. 2014, 79, 10561−10567. (d) Zhang, J.; Wu, D.; Chen, X.;
Liu, Y.; Xu, Z. J. Org. Chem. 2014, 79, 4799−4808.
ACKNOWLEDGMENTS
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Financial support from the Department of Science and
Technology, DST (No. SB/FT/CS-006/2013), and the Council
of Scientific and Industrial Research, CSIR (No. 02(0219)/14/
EMR-II), is gratefully acknowledged. We also thank DST, India,
and the Federal Ministry of Science, Research and Economy
(BMWFW) of Austria for financial support under an Indo−
Austrian joint project (No. INT/AUA/BMWF/P-26/2015).
(15) For a gold-catalyzed tandem [3,3]-propargyl ester rearrangement
approach, see: Wang, L.-J.; Zhu, H.-T.; Wang, A.-Q.; Qiu, Y.-F.; Liu, X.-
Y.; Liang, Y.-M. J. Org. Chem. 2014, 79, 204−212.
(16) For selected examples of hydration of alkynes, see: (a) Liang, S.;
Jasinski, J.; Hammond, G. B.; Xu, B. Org. Lett. 2015, 17, 162−165.
(b) Wang, W.; Zheng, A.; Zhao, P.; Xia, C.; Li, F. ACS Catal. 2014, 4,
321−327. (c) Jadhav, A. M.; Gawade, S. A.; Vasu, D.; Dateer, R. B.; Liu,
R.-S. Chem. - Eur. J. 2014, 20, 1813−1817. (d) Xu, C.; Du, W.; Zeng, Y.;
Dai, B.; Guo, H. Org. Lett. 2014, 16, 948−951.
DEDICATION
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This paper is dedicated to Professor J. Carlos Menen
occasion of his 56th birthday.
́
dez on the
(17) Zhang, Z.; Wu, L.; Liao, J.; Wu, W.; Jiang, H.; Li, J.; Li, J. J. Org.
Chem. 2015, 80, 7594−7603.
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