LETTER
Polysubstituted Pyrroles from Enamine Esters and Ketones
2533
O
Ο
MeO2C
Ph
CO2Et
EtO2C
CO2Et
OMe
OEt
+
+
N
Bn
N
HN
Bn
Ph
HN
Bn
Bn
3h
1o
1h
3ho
equiv
1
1
1
:
:
:
1
4
6
3.5
1
1
:
:
:
1
3
6.5
Scheme 3 Reagents and conditions: PhI(OAc)2 (1.1 equiv), BF3·OEt2 (0.2 equiv).
2008, 10, 2629. (i) Wang, Y.-F.; Toh, K. K.; Chiba, S.;
Narasaka, K. Org. Lett. 2008, 10, 5019. (j) Liu, X.; Huang,
L.; Zheng, F.; Zhan, Z. Adv. Synth. Catal. 2008, 350, 2778.
(k) Queiroz, M. J. R. P.; Begouin, A.; Pereira, G.; Ferreira,
P. M. T. Tetrahedron 2008, 64, 10714. (l) Alcaide, B.;
Almendros, P.; Carrascosa, R.; Redondo, M. C. Chem. Eur.
J. 2008, 14, 637. (m) Tan, B.; Shi, Z.; Chua, P. J.; Li, Y.;
Zhong, G. Angew. Chem. Int. Ed. 2009, 48, 758. (n) Lygin,
A. V.; Larionov, O. V.; Korotkov, V. S.; de Meijere, A.
Chem. Eur. J. 2009, 15, 227. (o) Tejedor, D.; Lõpez-Tosco,
S.; Gozález-Platas, J.; Garcia-Tellado, F. Chem. Eur. J.
2009, 15, 838. (p) Kim, Y.; Kim, J.; Park, S. B. Org. Lett.
2009, 11, 17.
MeO2C
CO2Et
Ph
EtO2C
CO2Me
Ph
EtO2C
CO2Me
Ph
N
N
N
H
Ph
Bn
56%
72%
82%
EtO2C
Ph
CO2Et
MeO2C
CO2Et
MeO2C
CO2Et
Ph
n-Pr
Ph
N
N
N
n-Bu
allyl
allyl
(6) (a) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102,
2523. (b) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008,
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K.; Kiyono, Y.; Maruyama, A.; Tohma, H.; Kita, Y. Chem.
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T.; Ito, M.; Motimoto, K.; Iwata, M.; Kita, Y. Angew. Chem.
Int. Ed. 2008, 47, 1301. (e) Kita, Y.; Norimoto, K.; Ito, M.;
Ogawa, C.; Goto, A.; Dohi, T. J. Am. Chem. Soc. 2009, 131,
1668.
(8) Yan, J.; Zhong, L. R.; Chen, Z. C. J. Org. Chem. 1991, 56,
49.
(9) Papoutsis, I.; Spyroudis, S.; Varvoglis, A. Tetrahedron
1998, 54, 1005.
(10) Koch, D.; Schafer, H. Angew. Chem. 1973, 85, 264.
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J. M. Tetrahedron 1983, 39, 793.
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Angew. Chem. Int. Ed. 2008, 47, 7230.
80%
78%
74%
Figure 2 Isolated yields based on 3-methyl or 3-propyl enamine
esters which were totally converted (see ref. 15 for experimental de-
tails)
Acknowledgment
We thank the National Natural Science Foundation of China (No.
20772053) for financial support.
References and Notes
(1) Fürstner, A. Angew. Chem. Int. Ed. 2003, 42, 3582.
(2) (a) Huffman, J. W. Curr. Med. Chem. 1999, 6, 705.
(b) Agarwal, S.; Cämmerer, S.; Filali, S.; Fröhner, W.;
Knöll, J.; Krahl, M. P.; Reddy, K. R.; Knölker, H. J. Curr.
Org. Chem. 2005, 9, 1601.
(3) Domingo, V. M.; Aleman, C.; Brillas, E.; Julia, L. J. Org.
Chem. 2001, 66, 4058.
(4) (a) Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 2001,
2491. (b) Balme, G. Angew. Chem. Int. Ed. 2004, 43, 6238.
(5) For some recent examples of pyrrole synthesis, see: (a) Su,
S.; Porco, J. A. Jr. J. Am. Chem. Soc. 2007, 129, 7744.
(b) St. Cyr, D. J.; Martin, N.; Arndtsen, B. A. Org. Lett.
2007, 9, 449. (c) Rivero, M. R.; Buchwald, S. L. Org. Lett.
2007, 9, 973. (d) Peng, L.; Zhang, X.; Ma, J.; Zhong, Z.;
Wang, J. Org. Lett. 2007, 9, 1445. (e) Istrate, F. M.;
Gagosz, F. Org. Lett. 2007, 9, 3181. (f) Chiba, S.; Wang,
Y.-F.; Lapointe, G.; Narasaka, K. Org. Lett. 2008, 10, 313.
(g) Attanasi, O. A.; Favi, G.; Filippone, P.; Giorgi, G.;
Mantellini, F.; Moscatelli, G.; Spinelli, D. Org. Lett. 2008,
10, 1983. (h) Cacchi, S.; Fabrizi, G.; Filisti, E. Org. Lett.
(14) Yu, W.; Du, Y.; Zhao, K. Org. Lett. 2009, 11, 2417.
(15) Procedures for the Preparation of Asymmetric Pyrroles
BF3·OEt2 (0.04 mmol) was added to a solution of 3-alkyl-
enamine esters (0.2 mmol) and 3-phenyl-enamine esters
(1.2 mmol) in 1 mL CH2Cl2, followed by DIB (0.22 mmol),
and the mixture was stirred at 0–10 °C. After the reaction
finished as indicated by TLC, the mixture was concentrated
under reduced pressure, and the residue was treated with
flash column chromatography to give the product.
Synlett 2009, No. 15, 2529–2533 © Thieme Stuttgart · New York