preparation. The known methods for the construction of the
pyrrole rings proceed either by traditional methods via various
types of cycloaddition or cycloisomerization of acyclic precur-
sors5 or by transition-metal-catalyzed reactions.6 There were also
reports concerning the preparation of acylpyrroles by double
condensation with amides.7 In the past few years, copper-
catalyzed aryl C-X bond (X ) N, O, S, etc.) formation
reactions through coupling between aryl halides and heterocen-
tered nucleophiles has drawn considerable attention,8 which
provides an excellent complement to the Pd-catalyzed reactions.
More recently, this methodology was successfully extended to
the synthesis of allenamides,8g enamides,9 and lactams8h by
coupling of amides with allenyl halides, vinyl halides, and
iodoenamides via intramolecular vinylation, respectively. It
could be envisioned that if a tandem vinylation could proceed
between an amide and a dienyl dihalide, it might provide a
straightforward route for the synthesis of pyrroles with various
substitutes. A palladium-catalyzed tandem alkenyl and aryl-
C-N bond formation was reported by Willis10 and double
N-arylation of amines by Nozaki.11 A number of copper-
catalyzed aryl-C-N bond formation has been reported. Reports
concerning alkenyl-C-N bond formation are also beginning to
appear.8h,9,12 However, no examples of a copper-catalyzed
Copper-Catalyzed Double N-Alkenylation of
Amides: An Efficient Synthesis of Di- or
Trisubstituted N-Acylpyrroles
Xiyuan Yuan, Xiaobing Xu, Xiaobo Zhou, Jiwei Yuan,
Lugen Mai, and Yanzhong Li*
Department of Chemistry and Shanghai Key Laboratory of
Green Chemistry and Chemical Processes, East China Normal
UniVersity, 3663 North Zhongshan Road,
Shanghai 200062, P. R. China
ReceiVed October 22, 2006
(5) For reviews, see: (a) Gossauer, A. Pyrrole. In Houben-Weyl;
Thieme: Stuttgart, 1994; E6a/1, p 556. (b) Gilchrist, T. L. J. Chem. Soc.,
Perkin Trans. 1999, 1, 2849. (c) Tarasova, O. A.; Nedolya, N. A.;
Vvedensky, V. Yu.; Brandsma, L.; Trofimov, B. A. Tetrahedron Lett. 1997,
38, 7241.
(6) For recent examples, see: (a) Kel’in, A. V.; Sromek, A. W.;
Gevorgyan, V. J. Am. Chem. Soc. 2001, 123, 2074. (b) Gabriele, B.; Salerno,
G.; Fazio, A. J. Org. Chem. 2003, 68, 7853. (c) Ramanathan, B.; Keith, A.
J.; Armstrong, D.; Odom, A. L. Org. Lett. 2004, 6, 2957. (d) Shen, H.-C.;
Li, C.-W.; Liu, R.-S. Tetrahedron Lett. 2004, 45, 9245. (e) Kamijo, S.;
Kanazawa, C.; Yamamoto, Y. J. Am. Chem. Soc. 2005, 127, 9260. (f) Gorin,
D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260. (g)
Larionov, O. V.; de Meijere, A. Angew. Chem., Int. Ed. 2005, 44, 5664.
(h) Alcaide, B.; Almendros, P.; Redondo, M. C. Chem. Commun. 2006,
2616.
(7) (a) Lee, S. D.; Brook, M. A.; Chan, T. H. Tetrahedron Lett. 1983,
24, 1569. (b) Saeed, M. T.; Rauf, A.; Osman, S. M. J. Chem. Res., Synop.
1989, 7, 222. (c) Tafel, K. A.; Bates, D. K. J. Org. Chem. 1992, 57, 3676.
(d) Bates, D. K.; Xia, M. J. Org. Chem. 1998, 63, 9190. (e) Evans, D. A.;
Borg, G.; Scheidt, K. A. Angew. Chem., Int. Ed. 2002, 41, 3188. (f) Ekkati,
A. R.; Bates, D. K. Synthesis 2003, 13, 1959.
An efficient copper-catalyzed double alkenylation of amides
with (1Z,3Z)-1,4-diiodo-1,3-dienes is reported for the first
time. The reactions proceed to afford di- or trisubstituted
N-acylpyrroles in good to excellent yields using CuI as the
catalyst, Cs2CO3 as the base, and rac-trans-N,N′-dimethyl-
cyclohexane-1,2-diamine as the ligand.
Pyrrole rings constitute an important class of heterocyclic
compounds,1 which represent not only useful building blocks
in the synthesis of natural products but also key structural units
in compounds that exhibit remarkable pharmacological activi-
ties.2,3 They have also found broad applications in the field of
material science.4 As a consequence, much attention has been
paid to the development of efficient methodologies for their
(8) For reviews, see: (a) Kunz, K.; Scholz, U.; Ganzer, D. Synlett 2003,
2428. (b) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42,
5400. For selected papers, see: (c) Klapars, A.; Antilla, J. C.; Huang, X.;
Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7727. (d) Cuny, G.; Bois-
Choussy, M.; Zhu, J. J. Am. Chem. Soc. 2004, 126, 14475. (e) Ley, S.;
Thomas, A. W.; Angew. Chem., Int. Ed. 2003, 42, 5400. (f) Ma, D.; Cai,
Q.; Zhang, H. Org. Lett. 2003, 5, 2453. (g) Trost, B. M.; Stiles, D. T. Org.
Lett. 2005, 7, 2117. (h) Hu, T.; Li, C. Org. Lett. 2005, 7, 2035. (i) Yang,
T.; Lin, C.; Fu, H.; Jiang, Y.; Zhao, Y. Org. Lett. 2005, 7, 4781. (j)Taniguchi,
N.; Onami, T. J. Org. Chem. 2004, 69, 915. (k) Klapars, A.; Paris, S.;
Anderson, K. W.; Buchwald, S. L. J. Am. Chem. Soc. 2004, 126, 3529. (l)
Antilla, J. C.; Baskin, J. M.; Barder, T. E.; Buchwald, S. L. J. Org. Chem.
2004, 69, 5578. (m) Cristau, H.-J.; Cellier, P. P.; Spimdler, J.-F.; Taillefer,
M. Eur. J. Org. Chem. 2004, 695. (n) Son, S. U.; Park, I. K.; Park, J.;
Hyeon, T. Chem. Commun. 2004, 778.
(9) Jiang, L.; Job, G. E.; Klapars, A.; Buchwald, S. L. Org. Lett. 2003,
5, 3667.
(10) Willis, M. C.; Brace, G. N.; Holmes, I. P. Angew. Chem., Int. Ed.
2005, 44, 403.
(11) Nozaki, K.; Takahashi, K.; Nakano, K.; Hiyama, T.; Tang, H.-Z.;
Fujiki, M.; Yamaguchi, S.; Tamao, K. Angew. Chem., Int. Ed. 2003, 42,
2051.
(1) For reviews, see: (a) Gribble, G. W. In ComprehensiVe Heterocyclic
Chemistry; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.;
Pergamon: Oxford, 1996; Vol. 2, p 207. (b) Joule, J. A.; Mills, K. In
Heterocyclic Chemistry; Blackwell Science: Oxford, UK, 2000.
(2) For recent reviews, see: (a) Fu¨rstner, A. Angew. Chem., Int. Ed. 2003,
42, 3582. (b) Hoffmann, H.; Lindel, T. Synthesis 2003, 1753. (c) Balme,
G. Angew. Chem., Int. Ed. 2004, 43, 6238. (d) Bellina, F.; Rossi, R.
Tetrahedron 2006, 62, 7213.
(3) See also: (a) Cramer, R. D.; Poss, M. A.; Hermsmeier, M. A.;
Caulfield, T. J.; Kowala, M. C.; Valentine, M. T. J. Med. Chem. 1999, 42,
3919. (b) Jacobi, P. A.; Coutts, L. D.; Guo, J.; Hauck, S. I.; Leung, S. H.
J. Org. Chem. 2000, 65, 205. (c) Andreani, A.; Cavalli, A.; Granaiola, M.;
Guardigli, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.;
Recanatini, M.; Roda, A. J. Med. Chem. 2001, 44, 4011. (d) Trippe´, G.;
Derf, F. L.; Lyskawa, J.; Mazari, M.; Roncali, J.; Gorgues, A.; Levillain,
E.; Salle´, M. Chem. Eur. J. 2004, 10, 6497. (e) Baraldi, P. G.; Nunez, M.
C.; Tabrizi, M. A.; De Clercq, E.; Balzarini, J.; Bermejo, J.; Esterez, F.;
Romagnodi, R. J. Med. Chem. 2004, 47, 2877. (f) Srivastava, S. K.; Shefali
Miller, C. N.; Aceto, M. D.; Traynor, J. R.; Lewis, J. W.; Husbands, S. M.
J. Med. Chem. 2004, 47, 6645.
(4) For a review of pyrrole structure in materials, see: Electronic
Materials: The Oligomer Approach; Mu¨llen, K., Wegner, G., Eds.; Wiley-
VCH: Weinheim, Germany, 1998.
(12) (a) Coleman, R. C.; Liu, P.-H. Org. Lett. 2004, 6, 577. (b) Pan, X.;
Cai, Q.; Ma, D.; Org. Lett. 2004, 6, 1809. (c) Han, C.; Shen, R.; Su, S.;
Porco-Jr, J. A. Org. Lett. 2004, 6, 27.
10.1021/jo062194s CCC: $37.00 © 2007 American Chemical Society
Published on Web 01/24/2007
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J. Org. Chem. 2007, 72, 1510-1513