regioisomers.1a,2,3c Recently, a number of syntheses based on
the palladium-mediated cyclization reactions described by Cossy
and other groups have been proved to be some of the most
efficient approaches.8
A Tandem Elimination-Cyclization-Suzuki
Approach: Efficient One-Pot Synthesis of
Functionalized
(Z)-3-(Arylmethylene)isoindolin-1-ones
Remarkable progress has been made in metal-catalyzed
reactions of gem-dihaloolefins,9 which provide convenient and
versatile routes to polysubstituted alkenes,10 enynes,11
polyynes,12 and carbo- or heterocycles.13-15 Ma et al. have
developed the first transition metal-catalyzed bicyclic carbo-
metalation reaction of gem-dibromides and afforded a prompt
construction for fused bicycles from gem-dihaloolefins.13 Re-
cently, Lautens and co-workers reported several novel and
elegant modular methods of indol synthesis via palladium- or
copper-catalyzed C-N/C-N or C-N/C-C coupling sequence
from gem-dihaloolefins.15
Caiyun Sun and Bin Xu*
Department of Chemistry, Shanghai UniVersity,
Shanghai 200444, China
ReceiVed June 06, 2008
During our program aimed at the convenient construction of
nitrogen-containing molecules and biochemical validation of
various heterocycles,16 our attention was drawn to 3-arylmeth-
yleneisoindolin-1-ones. Thus, gem-dihaloolefins were explored
as substrates to provide a general approach for a broad range
of heterocycles under palladium-catalyzed reaction. Herein, we
(5) (a) Dominh, T.; Johnson, A. L.; Jones, J. E.; Senise, P. P., Jr. J. Org.
Chem. 1977, 42, 4217. (b) Grigg, R.; Gunaratne, H. Q. N.; Sridharan, V. J. Chem.
Soc., Chem. Commun. 1985, 1183. (c) Takahashi, I.; Kawakami, T.; Hirano, E.;
Yokota, H.; Kitajima, H. Synlett 1996, 353. (d) Takahashi, I.; Hatanaka, M.
Heterocycles 1997, 45, 2475.
(6) (a) Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 1432. (b) Koradin,
C.; Dohle, W.; Rodriguez, A. L.; Schmid, B.; Knochel, P. Tetrahedron 2003,
59, 1571.
A novel and efficient one-pot regioselective elimination-
cyclization-Suzuki approach was developed to afford (Z)-
3-arylmethyleneisoindolin-1-ones in good to excellent yields
from easily accessible o-gem-dihalovinylbenzamides and
organoboron reagents.
(7) (a) Lin, C.-F.; Yang, J.-H.; Hsieh, P.-C.; Lu, W.-D.; Wu, M.-J. J. Chin.
Chem. Soc. (Taipei, Taiwan) 2001, 48, 211. (b) Lu, W.-D.; Lin, C.-F.; Wang,
C.-J.; Wang, S.-J.; Wu, M.-J. Tetrahedron 2002, 58, 7315.
(8) (a) Khan, M. W.; Kundu, N. G. Synlett 1997, 1435. (b) Couty, S.; Lie´gault,
B.; Meyer, C.; Cossy, J. Org. Lett. 2004, 6, 2511. (c) Couty, S.; Lie´gault, B.;
Meyer, C.; Cossy, J. Tetrahedron 2006, 62, 3882. (d) Batchu, V. R.; Barange,
D. K.; Kumar, D.; Sreekanth, B. R.; Vyas, K.; Reddy, E. A.; Pal, M. Chem.
Commun. 2007, 1966.
(9) For reviews of gem-dihaloolefins, see: (a) Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York,
2002; p 650. (b) Xu, B.; Ma, S. Chin. J. Org. Chem. 2001, 21, 252.
(10) For more recent work, see: (a) Minato, A.; Suzuki, K.; Tamao, K. J. Am.
Chem. Soc. 1987, 109, 1257. (b) Roush, W. R.; Koyama, K.; Curtin, M. L.;
Moriarty, K. J. J. Am. Chem. Soc. 1996, 118, 7502. (c) Shen, W.; Wang, L. J.
Org. Chem. 1999, 64, 8873. (d) Shen, W. Synthesis 2000, 737. (e) Zeng, X.;
Qian, M.; Hu, Q.; Negishi, E. Angew. Chem., Int. Ed. 2004, 43, 2259. (f)
Molander, G. A.; Yokoyama, Y. J. Org. Chem. 2006, 71, 2493. (g) Knorr, R.;
Pires, C.; Freudenreich, J. J. Org. Chem. 2007, 72, 6084.
3-Arylmethyleneisoindolin-1-ones represent important struc-
tural units frequently found in natural products, biologically
active compounds, and other synthetic intermediates.1 Consider-
able effort has been made to synthesize 3-arylmethyleneisoin-
dolin-1-ones due to their wide application in pharmaceutical
research. Among the various synthetic strategies, the majority
of synthetic routes rely on nucleophilic addition to phthalimides2
or phthalides,3 condensation reaction from 3-(diphenylphos-
phinoyl)isoindolin-1-ones1a,4 or phthalaldehyde,4c,5 and base-
promoted nucleophilic addition of o-(1-alkynyl)benzamides6 or
benzonitrile derivatives.7 However, in the case of unsymmetrical
substrates, these approaches often lead to a mixture of
(11) For more recent work, see: (a) Zeng, X.; Hu, Q.; Qian, M.; Negishi, E.
J. Am. Chem. Soc. 2003, 125, 13636. (b) Shi, J.; Zeng, X.; Negishi, E. Org.
Lett. 2003, 5, 1825. (c) Negishi, E.; Shi, J.; Zeng, X. Tetrahedron 2005, 61,
9886.
(1) (a) Couture, A.; Deniau, E.; Grandclaudon, P. Tetrahedron 1997, 53,
10313, and references cited therein. (b) Kundu, N. G.; Khan, M. W. Tetrahedron
2000, 56, 4777, and references cited therein. (c) Comins, D. L.; Schilling, S.;
Zhang, Y. C. Org. Lett. 2005, 7, 95. (d) Lamblin, M.; Couture, A.; Deniau, E.;
Grandclaudon, P. Tetrahedron 2006, 62, 2917. (e) Lamblin, M.; Couture, A.;
Deniau, E.; Grandclaudon, P. Org. Biomol. Chem. 2007, 5, 1466.
(12) For more recent work, see: (a) Shen, W.; Thomas, S. A. Org. Lett. 2000,
2, 2857. (b) Hwang, G. T.; Son, H. S.; Ku, J. K.; Kim, B. H. Org. Lett. 2001,
3, 2469. (c) Hwang, G. T.; Son, H. S.; Ku, J. K.; Kim, B. H. J. Am. Chem. Soc.
2003, 125, 11241. (d) Kabalka, G. W.; Dong, G.; Venkataiah, B. Tetrahedron
Lett. 2005, 46, 763. (e) Gholami, M.; Melin, F.; McDonald, R.; Ferguson, M. J.;
Echegoyen, L.; Tykwinski, R. R. Angew. Chem., Int. Ed. 2007, 43, 9081. (f)
Bandyopadhyay, A.; Varghese, B.; Hopf, H.; Sankararaman, S. Chem. Eur. J.
2007, 13, 3813.
(2) Sa´nchez-Sa´nchez, C.; Pe´rez-Inestrosa, E.; Garc´ıa-Segura, R.; Suau, R.
Tetrahedron 2002, 58, 7267.
(3) (a) Cid, H. M. B.; Traenkle, C.; Baumann, K.; Pick, R.; Mies-Klomfass,
E.; Kostenis, E.; Mohr, K.; Holzgrabe, U. J. Med. Chem. 2000, 43, 2155. (b)
Katritzky, A. R.; He, H.-Y.; Jiang, R. Tetrahedron Lett. 2002, 43, 2831. (c)
Lamblin, M.; Couture, A.; Deniau, E.; Grandclaudon, P. Synthesis 2006, 1333.
(4) (a) Couture, A.; Deniau, E.; Grandclaudon, P.; Hoarau, C. Tetrahedron
2000, 56, 1491. (b) Couture, A.; Deniau, E.; Grandclaudon, P.; Hoarau, C.; Rys,
V. Tetrahedron Lett. 2002, 43, 2207. (c) Couture, A.; Deniau, E.; Grandclaudon,
P.; Rybalko-Rosen, H.; Le´once, S.; Pfeiffer, B.; Renard, P. Bioorg. Med. Chem.
Lett. 2002, 12, 3557. (d) Rys, V.; Couture, A.; Deniau, E.; Grandclaudon, P.
Tetrahedron 2003, 59, 6615. (e) Moreau, A.; Couture, A.; Deniau, E.;
Grandclaudon, P. J. Org. Chem. 2004, 69, 4527.
(13) (a) Ma, S.; Xu, B. J. Org. Chem. 1998, 63, 9156. (b) Ma, S.; Xu, B.;
Ni, B. J. Org. Chem. 2000, 65, 8532.
(14) For more recent work, see: (a) Larock, R. C.; Doty, M. J.; Han, X. J.
Org. Chem. 1999, 64, 8770. (b) Huh, D. H.; Ryu, H.; Kim, Y. G. Tetrahedron
2004, 60, 9857.
(15) (a) Wang, L.; Shen, W. Tetrahedron Lett. 1998, 39, 7625. (b) Fang,
Y.-Q.; Lautens, M. Org. Lett. 2005, 7, 3549. (c) Yuen, J.; Fang, Y.-Q.; Lautens,
M. Org. Lett. 2006, 8, 653. (d) Fayol, A.; Fang, Y.-Q.; Lautens, M. Org. Lett.
2006, 8, 4203. (e) Fang, Y.-Q.; Karisch, R.; Lautens, M. J. Org. Chem. 2007,
72, 1341. (f) Nagamochi, M.; Fang, Y.-Q.; Lautens, M. Org. Lett. 2007, 9, 2955.
(g) Fang, Y.-Q.; Lautens, M. J. Org. Chem. 2008, 73, 538.
10.1021/jo801219j CCC: $40.75
Published on Web 08/13/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 7361–7364 7361