Organic Letters
Letter
Chem. Soc. 2012, 134, 11372. (n) Hu, Y.; Xie, Y.; Shen, Z.; Huang, H.
Angew. Chem., Int. Ed. 2017, 56, 2473.
(3) (a) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004,
126, 9542. (b) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc.
2004, 126, 2300. (c) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am. Chem.
Soc. 2005, 127, 7690. (d) Ney, J. E.; Wolfe, J. P. J. Am. Chem. Soc. 2005,
In summary, we have developed a new strategy for
dehydrogenative difunctionalization of alkenes, which does not
need to suppress β-hydride elimination, thus obviating the use of
strong oxidants.13 After identifying that aminal can play a dual
role acting as a nucleophile and a mild oxidant, a palladium-
catalyzed aminomethylamination of aminoalkenes was estab-
lished using this strategy, providing a novel synthetic method to
2-(2-aminoethyl)indoles and 2-(2-aminoethyl)pyrrolidines. As
demonstrated by the given synthetic applications, the method
provides an efficient means to access indole-annulated hetero-
cycles, with relevance to both natural product and bioactive
molecule synthesis. Ongoing studies are focused on exploring the
scope of this reactivity and probing the catalytic mechanism.
127, 8644. (e) Streuff, J.; Hovelmann, C. H.; Nieger, M.; Muniz, K. J.
̈
̃
Am. Chem. Soc. 2005, 127, 14586. (f) Liu, G.; Stahl, S. S. J. Am. Chem.
Soc. 2006, 128, 7179. (g) Desai, L. V.; Sanford, M. S. Angew. Chem., Int.
Ed. 2007, 46, 5737−5740. (h) Shi, X.; Mandel, S. M.; Platz, M. S. J. Am.
Chem. Soc. 2007, 129, 4542. (i) Kalyani, D.; Sanford, M. S. J. Am. Chem.
Soc. 2008, 130, 2150. (j) Rosewall, C. F.; Sibbald, P. A.; Liskin, D. V.;
Michael, F. E. J. Am. Chem. Soc. 2009, 131, 9488. (k) Wu, T.; Yin, G.; Liu,
G. J. Am. Chem. Soc. 2009, 131, 16354. (l) Kalyani, D.; Satterfield, A. D.;
Sanford, M. S. J. Am. Chem. Soc. 2010, 132, 8419. (m) Qiu, S.; Xu, T.;
Zhou, J.; Guo, Y.; Liu, G. J. Am. Chem. Soc. 2010, 132, 2856.
(n) Satterfield, A. D.; Kubota, A.; Sanford, M. S. Org. Lett. 2011, 13,
1076. (o) McMurtrey, K. B.; Racowski, J. M.; Sanford, M. S. Org. Lett.
2012, 14, 4094. (p) Ingalls, E. L.; Sibbald, P. A.; Kaminsky, W.; Michael,
F. E. J. Am. Chem. Soc. 2013, 135, 8854. (q) Zhu, H.; Chen, P.; Liu, G. J.
Am. Chem. Soc. 2014, 136, 1766. (r) Cheng, J.; Qi, X.; Li, M.; Chen, P.;
Liu, G. J. Am. Chem. Soc. 2015, 137, 2480. (s) Chen, C.; Chen, P.; Liu, G.
J. Am. Chem. Soc. 2015, 137, 15648.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
Experimental details and full spectroscopic data for all new
X-ray structure of 3aa (CIF)
X-ray structure of 3ta (CIF)
X-ray structure of 3ua (CIF)
(4) For reviews on palladium-catalyzed oxidative amination of alkenes,
see: (a) Zeni, G.; Larock, R. C. Chem. Rev. 2006, 106, 4644. (b) Muller,
̈
T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008,
108, 3795. (c) Huang, L.; Arndt, M.; Gooßen, K.; Heydt, H.; Gooßen, L.
J. Chem. Rev. 2015, 115, 2596.
(5) (a) Katritzky, A. R.; Shobana, N.; Harris, P. A. Tetrahedron Lett.
1991, 32, 4247. (b) Tan, C. Y. K.; Wainman, D.; Weaver, D. F. Bioorg.
Med. Chem. 2003, 11, 113. (c) Wang, X.; Li, J.; Zhang, Y. Synth. Commun.
2003, 33, 3575. (d) Katritzky, A. R.; Manju, K.; Singh, S. K.; Meher, N.
K. Tetrahedron 2005, 61, 2555. (e) Hatano, B.; Nagahashi, K.; Kijima, T.
J. Org. Chem. 2008, 73, 9188.
(6) (a) Xie, Y.; Hu, J.; Wang, Y.; Xia, C.; Huang, H. J. Am. Chem. Soc.
2012, 134, 20613. (b) Xie, Y.; Hu, J.; Xie, P.; Qian, B.; Huang, H. J. Am.
Chem. Soc. 2013, 135, 18327. (c) Hu, J.; Xie, Y.; Huang, H. Angew.
Chem., Int. Ed. 2014, 53, 7272. (d) Qin, G.; Li, L.; Li, J.; Huang, H. J. Am.
Chem. Soc. 2015, 137, 12490. (e) Zhang, G.; Gao, B.; Huang, H. Angew.
Chem., Int. Ed. 2015, 54, 7657. (f) Li, J.; Qin, G.; Liu, Y.; Huang, H. Org.
Chem. Front. 2016, 3, 259. (g) Liu, Y.; Xie, Y.; Wang, H.; Huang, H. J.
Am. Chem. Soc. 2016, 138, 4314. (h) Li, L.; Liu, P.; Su, Y.; Huang, H. Org.
Lett. 2016, 18, 5736.
(7) For selected reviews on indole, see: (a) Humphrey, G. R.; Kuethe,
J. K. Chem. Rev. 2006, 106, 2875. (b) Bandini, M.; Eichholzer, A. Angew.
Chem., Int. Ed. 2009, 48, 9608. (c) Kruger, K.; Tillack, A.; Beller, M. Adv.
Synth. Catal. 2008, 350, 2153. (d) Platon, M.; Amardeil, R.; Djakovitch,
L.; Hierso, J.-C. Chem. Soc. Rev. 2012, 41, 3929.
(8) CCDC 1558678 (3aa), 1558689 (3ta), and 1558679 (3ua)
contain the supplementary crystallographic data for this paper. This data
can be obtained free of charge from The Cambridge Crystallographic
(9) Huang, Y.-Y.; Cai, C.; Yang, X.; Lv, Z.-C.; Schneider, U. ACS Catal.
2016, 6, 5747−5763.
(10) (a) Whitehead, J. W. F.; Mills, K.; Coates, I. H.; Oxford, A. W.;
North, P. C. Patent Appl. US005196534A, 1993. (b) Coates, I. H.;
Oxford, A. W.; North, P. C.; Tyers, M. B. Patent Appl. US005221687A,
1993. (c) Cooper, S. J.; Coates, I. H.; Oxford, A. W.; North, P. C. Patent
Appl. US005221687A, 1993.
(11) Miao, B.; Li, S.; Li, G.; Ma, S. Org. Lett. 2016, 18, 2556.
(12) Zhang, Y.; Zheng, J.; Cui, S. J. Org. Chem. 2014, 79, 6490.
(13) The enamide intermediate was isolated and could be directly
converted into the desired product with aminal, suggesting that the
enamide intermediate like C was most likely involved in our catalytic
AUTHOR INFORMATION
■
Corresponding Author
ORCID
Author Contributions
L.L. and X.Z. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by the CAS Interdisciplinary
Innovation Team, the National Natural Science Foundation of
China (21672199).
REFERENCES
■
(1) For leading reviews on Pd-catalyzed alkene difunctionalization
reactions, see: (a) Wolfe, J. P. Eur. J. Org. Chem. 2007, 2007, 571.
(b) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem.
Rev. 2007, 107, 5318. (c) Jensen, K. H.; Sigman, M. S. Org. Biomol.
Chem. 2008, 6, 4083. (d) McDonald, R. I.; Liu, G.; Stahl, S. S. Chem. Rev.
2011, 111, 2981. (e) Sigman, M. S.; Werner, E. W. Acc. Chem. Res. 2012,
45, 874. (f) Yin, G.; Mu, X.; Liu, G. Acc. Chem. Res. 2016, 49, 2413.
(2) (a) Backvall, J.-E. In Metal-Catalyzed Cross-Coupling Reactions, 2nd
̈
ed.; de Meijere, A., Diederich, F., Eds.; Wiley-VCH: Hoboken, NJ, 2004;
p 479. (b) Backvall, J.-E.; Bystroem, S. E.; Nordberg, R. E. J. Org. Chem.
̈
1984, 49, 4619. (c) Backvall, J.-E.; Nystroem, J. E.; Nordberg, R. E. J.
̈
Am. Chem. Soc. 1985, 107, 3676. (d) Zhang, Y.; Sigman, M. S. J. Am.
Chem. Soc. 2007, 129, 3076. (e) Du, H.; Zhao, B.; Shi, Y. J. Am. Chem.
Soc. 2008, 130, 8590. (f) Du, H.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2008,
130, 8590. (g) Li, Y.; Song, D.; Dong, V. M. J. Am. Chem. Soc. 2008, 130,
2962. (h) Wang, A.; Jiang, H.; Chen, H. J. Am. Chem. Soc. 2009, 131,
3846. (i) Urkalan, K. B.; Sigman, M. S. Angew. Chem., Int. Ed. 2009, 48,
3146. (j) Jensen, K. H.; Webb, J. D.; Sigman, M. S. J. Am. Chem. Soc.
2010, 132, 17471. (k) Werner, E. W.; Urkalan, K. B.; Sigman, M. S. Org.
Lett. 2010, 12, 2848. (l) Liao, L.; Jana, R.; Urkalan, K. B.; Sigman, M. S. J.
Am. Chem. Soc. 2011, 133, 5784. (m) Saini, V.; Sigman, M. S. J. Am.
D
Org. Lett. XXXX, XXX, XXX−XXX