Table 3 Synthesis of N-aryl and N-alkyloxindolesa
Notes and references
1 (a) L. Sun, N. Tran, F. Tang, H. App, P. Hirth, G. McMahon and
C. Tang, J. Med. Chem., 1998, 41, 2588; (b) E. R. Wood,
L. Kuyper, K. G. Petrov, R. N. Hunter III, P. A. Harris and
K. Lackey, Bioorg. Med. Chem. Lett., 2004, 14, 953;
(c) H. Masamune, J. B. Cheng, K. Cooper, J. F. Eggier,
A. Marfat, S. C. Marshall, J. T. Shirley, J. E. Tickner,
J. P. Umland and E. Vazquez, Bioorg. Med. Chem. Lett., 1995,
5, 1965; (d) R. P. Robinson, L. A. Reiter, W. E. Barth,
A. M. Campeta, K. Cooper, B. J. Cronin, R. Destito,
K. M. Donahue, F. C. Falkner, E. F. Fiese, D. L. Johnson,
A. V. Kuperman, T. E. Liston, D. Malloy, J. J. Martin,
D. Y. Mitchell, F. W. Rusek, S. L. Shamblin and C. F. Wright,
J. Med. Chem., 1996, 39, 10.
Entry
Substrate
Product
Yield (%)
E : Z
1
80
5.5 : 1
2 Recent examples, see; (a) A. Millemaggi, A. Perry,
A. C. Whitwood and R. J. K. Taylor, Eur. J. Org. Chem., 2009,
2947; (b) R. T. Ruck, M. A. Huffman, M. M. Kim, M. Shevlin,
W. V. Kandur and I. W. Daries, Angew. Chem., Int. Ed., 2008, 47,
4711; (c) Y.-X. Jia, J. M. Hillgren, E. L. Watson, S. P. Marsden
and E. P. Kundig, Chem. Commun., 2008, 4040; (d) S. Tang,
¨
Q.-F. Yu, P. Peng, J.-H. Li, P. Zhong and R.-Y. Tang, Org. Lett.,
2007, 9, 3413; (e) B. Lu and D. Ma, Org. Lett., 2006, 8, 6115;
(f) D. Tomita, K. Yamatsugu, M. Kanai and M. Shibasaki, J. Am.
2
3
43
—
Chem. Soc., 2009, 131, 6946; (g) E. P. Kundig, T. M. Seidel,
¨
Y.-X. Jia and G. Bernardinelli, Angew. Chem., Int. Ed., 2007, 46,
8484; (h) Y. Yasui, H. Kamisaki and Y. Takemoto, Org. Lett.,
2008, 10, 3303; (i) T. Miura, T. Toyoshima, Y. Takahashi and
M. Murakami, Org. Lett., 2009, 11, 2141; (j) R. R. Poondra and
N. J. Turner, Org. Lett., 2005, 7, 863; (k) T. Miura, T. Toyoshima,
Y. Takahashi and M. Murakami, Org. Lett., 2008, 10, 4887;
(l) S. P. Marsden, E. L. Watson and S. A. Raw, Org. Lett., 2008,
10, 2905; (m) F.-X. Felpin, O. Ibarguren, L. Nassar-Hardy and
E. Fouquet, J. Org. Chem., 2009, 74, 1349; (n) J. M. Hillgren and
S. P. Marsden, J. Org. Chem., 2008, 73, 6459.
41
73
5.3 : 1
6.8 : 1
4
3 Reviews, see; (a) X. Chen, K. M. Engle, D.-H. Wang and J.-Q. Yu,
Angew. Chem., Int. Ed., 2009, 48, 5094; (b) J.-Q. Yu, R. Giri and
X. Chen, Org. Biomol. Chem., 2006, 4, 4041.
4 Relevant copper-mediated synthesis of oxindoles by aromatic C–H
functionalisation, see; (a) Y.-X. Jia and E. P. Kundig, Angew.
Chem., Int. Ed., 2009, 48, 1636; (b) A. Perry and R. J. K. Taylor,
Chem. Commun., 2009, 3249.
a
¨
Reaction conditions: 3 (0.3 mmol), Pd catalyst (10 mol%) and
oxidant (0.6 mmol) in solvent (0.6 ml).
5 E. J. Hennessy and S. L. Buchwald, J. Am. Chem. Soc., 2003, 125,
12084.
6 (a) T. S. Jiang, R. Y. Tang, X. G. Zhang, X. H. Li and J. H. Li,
J. Org. Chem., 2009, 74, 8834; (b) A. Pinto, L. Neuville and J. Zhu,
Angew. Chem., Int. Ed., 2007, 46, 3291; (c) A. Pinto, L. Neuville,
P. Retailleau and J. Zhu, Org. Lett., 2006, 8, 4927; (d) P. Peng,
B.-X. Tang, S.-F. Pi, Y. Liang and J.-H. Li, J. Org. Chem., 2009,
74, 3569; (e) S. Tang, P. Peng, Z.-Q. Wang, B.-X. Tang,
C.-L. Deng, J.-H. Li, P. Zhong and N.-X. Wang, Org. Lett.,
2008, 10, 1875; (f) D.-J. Tang, B.-X. Tang and J.-H. Li, J. Org.
Chem., 2009, 74, 6749.
Scheme 3 Oxidative cyclization of Z-olefin 5.
7 (a) M. wasa and J.-Q. Yu, J. Am. Chem. Soc., 2008, 130, 14058;
(b) T. Miura, Y. Ito and M. Murakami, Chem. Lett., 2009, 38, 328.
8 (a) S. Ueda and H. Nagasawa, Angew. Chem., Int. Ed., 2008, 47, 6411;
(b) S. Ueda and H. Nagasawa, J. Org. Chem., 2009, 74, 4272;
(c) S. Ueda and H. Nagasawa, J. Am. Chem. Soc., 2009, 131, 15080.
9 (a) E. M. Ferreira and B. M. Stoltz, J. Am. Chem. Soc., 2003, 125,
9578; (b) H. Zhang, E. M. Ferreira and B. M. Stoltz, Angew.
Chem., Int. Ed., 2004, 43, 6144; (c) E. M. Ferreira, H. Zhang and
B. M. Stoltz, Tetrahedron, 2008, 64, 5987.
isomers of 3-arylidenyloxindoles in ratios of 4.9–6.8 : 1.
However, the reaction of Z-olefin substrate 5 under identical
conditions gave the product 2a in a similar E : Z ratio
(Scheme 3). These results suggest that the reaction products
E- and Z-3-arylidenyloxindoles are in equilibrium under the
reaction conditions.12 This configurational ambiguity compli-
cates interpretation of the reaction mechanism based on
product stereochemistry.13
10 A. J. Bingham, L. K. Dyall, R. O. C. Norman and C. B. Thomas,
J. Chem. Soc. C, 1970, 1879.
11 (a) C. Zhou and R. C. Larock, J. Am. Chem. Soc., 2004, 126, 2302;
(b) C. Jia, W. Lu, J. Oyamada, T. Kitamura, K. Matsuda, M. Irie
and Y. Fujiwara, J. Am. Chem. Soc., 2000, 122, 7252.
12 It is known that 3-arylidenyloxindoles are readily isomerized under
certain conditions to predominantly form the thermodynamically
stable isomer. See ref. 1a.
13 The reaction of a substrate with an electron-withdrawing nitro
group on the anilide arene (4-nitro cinnamanilide) gave only
recovered starting material, suggesting deprotonative metallation
of path A would be unfavorable.
In summary, we have developed a direct synthesis of
3-alkylideneoxindoles based on palladium-catalyzed aromatic
C–H activation/alkenylation. The reaction can be used for the
synthesis of NH free, N-aryl and N-alkyl oxindoles, thus
providing structurally diverse 3-alkylideneoxindoles from
readily accessible starting materials.
We thank Dr K. L. Kirk (NIDDK, NIH) for helpful
suggestions and Ms Emi Inaba for her technical assistance.
ꢀc
This journal is The Royal Society of Chemistry 2010
2464 | Chem. Commun., 2010, 46, 2462–2464