A. Pinto et al. / Tetrahedron Letters 50 (2009) 3602–3605
3605
Ar2
Schnapp, G.; Walter, R.; Heckel, A.; van Meel, J.; Rieder, C. L.; Peters, J. M. J. Cell.
Biol. 2003, 161, 281–294; (c) Noble, M. E. M.; Endicott, J. A.; Johnson, L. N.
Science 2004, 303, 1800–1805.
Ar1
O
R1
2. Indium-promoted (a) Yanada, R.; Obika, S.; Oyama, M.; Takemoto, Y. Org. Lett.
2004, 6, 2825–2828; (b) Yanada, R.; Obika, S.; Inokuma, T.; Yanada, K.;
Yamashita, M.; Ohta, S.; Takemoto, Y. J. Org. Chem. 2005, 70, 6972–6975;
Palladium-catalyzed (c) D’Souza, D. M.; Rominger, F.; Müller, T. J. J. Angew.
Chem., Int. Ed. 2005, 44, 153–158; (d) Cheung, W. S.; Patch, R. J.; Player, M. R. J.
Org. Chem. 2005, 70, 3741–3744; (e) Dai, W. M.; Shi, J.; Wu, J. Synlett 2008,
2716–2720; Rhodium-catalyzed (f) Shintani, R.; Yamagami, T.; Hayashi, T. Org.
Lett. 2006, 8, 4799–4801.
3. Palladium-catalyzed (a) Kamijo, S.; Sasaki, Y.; Kanazawa, C.; Schüsseler, T.;
Yamamoto, Y. Angew. Chem., Int. Ed. 2005, 44, 7718–7721; (b) Miaura, T.;
Toyoshima, T.; Takahashi, Y.; Murakami, M. Org. Lett. 2008, 10, 4887–4889;
Rhodium-catalyzed (c) Miura, T.; Takahashi, Y.; Murakami, M. Org. Lett. 2007, 9,
5075–5077.
R1
Ar1
Br
N
2
Pd(0)
R
1
R
Ar2
Ar1
N
O
R1
3
H
Pd
+
PdBr
R1
Cs2CO3
A
N
R
O
CsBr
H2O, CO2
F
R1
Pd
N
Ar1
Ar2
Ar1
X
4. Tang, S.; Yu, Q.-F.; Peng, P.; Li, J.-H.; Zhong, P.; Tang, R.-Y. Org. Lett. 2007, 9,
3413–3416.
5. See also (a) Marcaccini, S.; Pepino, R.; Marcos, C. F.; Polo, C.; Torroba, T. J.
Heterocycl. Chem. 2000, 1501–1503; (b) Wang, L.; Zhang, Y.; Hu, H.-Y.; Fun, H.
K.; Xu, J.-H. J. Org. Chem. 2005, 70, 3850–3858.
Pd
R
Ar1
R1
B
O
N
R
O
6. Pinto, A.; Neuville, L.; Retailleau, P.; Zhu, J. Org. Lett. 2006, 8, 4927–4930.
7. (a) Tang, S.; Peng, P.; Pi, S. F.; Liang, Y.; Wang, N. X.; Li, J. H. Org. Lett.
2008, 10, 1179–1182; (b) Tang, S.; Peng, P.; Wang, Z. Q.; Tang, B. X.;
Deng, C. L.; Li, J. H.; Zhong, P.; Wang, N. X. Org. Lett. 2008, 10, 1875–
1878; (c) Tang, S.; Peng, P.; Zhong, P.; Li, J. H. J. Org. Chem. 2008, 73,
5476–5480.
8. Pinto, A.; Neuville, L.; Zhu, J. Angew. Chem., Int. Ed 2007, 46, 3291–3295.
9. (a) Bonnaterre, F.; Bois-Choussy, M.; Zhu, J. Org. Lett. 2006, 8, 4351–4354; (b)
Pinto, A.; Jia, X.; Neuville, L.; Zhu, J. Chem. Eur. J. 2007, 13, 961–967.
10. (a) Cuny, G.; Bois-Choussy, M.; Zhu, J. Angew. Chem., Int. Ed. 2003, 42, 4774–
4777; (b) Cuny, G.; Bois-Choussy, M.; Zhu, J. J. Am. Chem. Soc. 2004, 126, 14475–
14484; (c) Salcedo, A.; Neuville, L.; Rondot, C.; Retailleau, P.; Zhu, J. Org. Lett.
2008, 10, 857–860; (d) Gerfaud, T.; Neuville, L.; Zhu, J. Angew. Chem., Int. Ed.
2009, 48, 572–577.
R1
E
N
R
O
Pd(0)
Ar2I
C
Ar2PdI
4
D
Scheme 2. Three-component synthesis of oxindole, mechanistic rationale. Ligand
associated with Pd was omitted for the sake of clarity.
OMe
11. Reviews on metal-catalyzed multicomponent reactions (a) Balme, G.;
Bossharth, E.; Monteiro, N. Eur. J. Org. Chem. 2003, 4101–4111; (b)
NO2
´
Murakami, M. Angew. Chem., Int. Ed. 2003, 42, 718–720; (c) DSouza, D. M.;
OMe
Müller, T. J. J. Chem. Soc. Rev. 2007, 36, 1095–1108; (d) Arndtsen, B. A. Chem.
Eur. J. 2009, 15, 302–312; (e) Müller, T. J. J. Top. Organomet. Chem. 2006, 19,
149–205.
Pd(OAc)2 cat.,
NaOAc, 4b,
O2N
O2N
12. (a) Hartwig, J. F.. In Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E.-I., de Meijere, A., Eds.; Wiley-Interscience: New York,
2002; Vol. 1, pp 1051–1096; (b) Muci, A. R.; Buchwald, S. L. Top Curr. Chem.
2002, 219, 133–205.
O
DMF, 110°C
N
N
O
88%
Me
(E)-1h
Me
5h
13. Yin, J.; Buchwald, S. L. Org. Lett. 2000, 2, 1101–1104.
14. We have previously determined that DMF is
a solvent of choice for the
Scheme 3. Synthesis of geometrically pure (E)-1h.
carbopalladation/C-H functionalization sequence, see Ref. 6.
15. Leclerc, J.-P.; André, M.; Fagnou, K. J. Org. Chem. 2006, 71, 1711–1714. and
references therein..
16. Lira, R.; Wolfe, J. P. J. Am. Chem. Soc. 2004, 126, 13906–13907.
17. Lipshutz, B. H.; Frieman, B.; Birkedal, H. Org. Lett. 2004, 6, 2305–2308.
18. Typical procedure: To a flame-dried flask were added N-methyl-3-phenylprop-
2-ynamide 3a (30 mg, 0.19 mmol, 1.0 equiv), 1-bromo-4-nitrobenzene 2a
(38 mg, 0.19 mmol, 1.0 equiv), Pd(OAc)2 (2.1 mg, 0.0095 mmol, 0.05 equiv),
Xantphos (3.3 mg, 0.0057 mmol, 0.03 equiv), and Cs2CO3 (186 mg, 0.57 mmol,
3.0 equiv). The flask was carefully deoxygenated and anhydrous 1,4 dioxane
(1 mL) was added. The mixture was stirred under argon atmosphere at 100 °C
for 6 h and then iodobenzene 4a (0.032 mL, 0.29 mmol, 1.5 equiv) in DMF
(1 mL) was added. After being stirred at 110 °C for 15 h, the reaction mixture
was quenched with saturated aqueous NaCl solution and was extracted with
EtOAc. The combined organic layers were washed with brine and dried
(Na2SO4), and then concentrated. The residue was purified by flash column
chromatography (heptanes/EtOAc = 4/1) to give 3-(diphenylmethylene)-1-
O
O
N
O
Pd
Ar
EWG
a
7
N
R
O
O
a
N
O
Pd
b
Ar
N
O
b
EWG
Pd
Ar
N
R
O
EWG
6
N
R
O
8
methyl-5-nitro-1,3-dihydro-2H-indol-2-one 1a (32.7 mg, 48%) as
a yellow
solid. mp: 225–229 °C. IR (neat, cmÀ1 1652, 1558, 1506, 1457, 617. 1H NMR
)
m
(CDCl3, 300 MHz): d 8.14 (dd, J = 8.7, 2.2 Hz, 1H), 7.62–7.30 (m, 10H), 7.28 (d,
J = 2.2 Hz, 1H), 6.84 (d, J = 8.7 Hz, 1H), 3.29 (s, 3H). 13C NMR (CDCl3, 75 MHz):
167.0, 159.2, 147.9, 142.8, 140.2, 139.0, 130.5, 130.4, 130.2, 129.5, 129.4, 128.1,
125.2, 123.8, 122.2, 118.9, 107.2, 26.5. HRMS (m/z, ESI+) calcd for
C22H16N2NaO3 ([M+Na]+) 379.1059, found 379.1052.
Scheme 4. Isomerization of carbopalladation adduct.
Acknowledgments
19. White, D. A.; Baizer, M. M. Tetrahedron Lett. 1973, 14, 3597–3600.
20. The stability of E- and Z-isomers depends on the substitution pattern of
oxindoles. In previous studies, we observed that E/Z isomerization readily
occurred with N-methyl-5-nitro-3-[phenyl)(2’-nitophenyl)methylene]indolin-
2-one. See Ref. 6.
21. (a) Zargarian, D.; Alper, H. Organometallics 1991, 10, 2914–2921; (b)
Dyker, G.; Kellner, A. Tetrahedron Lett. 1994, 35, 7633–7636; (c) de Vaal,
P.; Dedieu, A. J. Organomet. Chem. 1994, 478, 121–129; (d) Gibbs, R. A.;
Krishnan, U.; Dolence, J. M.; Poulter, C. D. J. Org. 1995, 60, 7821–7829;
(e) Ji, J.; Wang, Z.; Lu, X. Organometallics 1996, 15, 2821–2828; (f)
Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, P. P. Eur. J. Org. Chem. 1999,
3305–3313.
Financial supports from CNRS and this institute are gratefully
acknowledged. A. P. thanks the ‘Ministère de l’Enseignement Supéri-
eur et de la Recherche’ for a doctoral fellowship.
References and notes
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