T. E. Glotova et al. / Tetrahedron Letters 51 (2010) 6189–6191
6191
R2
R1
R2
R1
O
R2
R2
O
O
H
Ph
R1
R1
5a-c
6a
O
N
N
O
O
N
O
N
Ph
-H2O
R1 = Ph, R2 = H
Ph
H
O
Ph
A
O
3a-c
O
Scheme 6. Tentative mechanism of pyrroles 5a–c and 6a formation.
O
O
H
O
O
H
N
O
O
Ph
NH
Ph
Ph
Ph
H
+
7
O
Ph
N
O
O
H
-H2O
Ph
Ph
N
H
O
O
O
OH
O
Ph
HO Ph
3a
8
9
10
11
12
Scheme 7. Tentative mechanism of pyrrole 7 formation.
4. Trofimov, B. A.; Mikhaleva, A. I.; Vasil’tsov, A. M.; Schmidt, E. Y.; Tarasova, O. A.;
Morozova, L. V.; Sobenina, L. N.; Preiss, T.; Henkelmann, J. Synthesis 2000, 1125.
5. (a) Tedeschi, R. J. Acetylene, 3rd ed.. In Encyclopedia of Physical Science and
Technology; Meyers, R. A., Ed.; Acad. Press: San Diego, 2001; Vol. 1, pp 55–89;
(b)Rappoport, Z., Liebman, J. F., Eds.The Chemistry of Hydroxylamines, Oximes
We have tried to optimize the yields of the pyrroles by thermol-
ysis of oxime 3a under milder conditions: reflux in benzene (10 h),
heating in DMSO (80–85 °C, 10 h), reflux in toluene in the presence
of 5 wt % CuBr or 1 wt % CuOTf2 (4 h). However, the reaction mix-
tures contained mainly enols, acetophenone, and unidentified olig-
omers, in none of the cases were any pyrroles detected (1H NMR).
In conclusion, unusual rearrangements of O-2-(acyl)vinylketox-
imes lead to 2- or 3-acylsubstituted pyrroles. The positions of the
acyl and aryl (hetaryl) substituents on the pyrrole ring are variable
depending on the reaction conditions, that is, the reaction can be
chemo- and regio-controlled. Despite the modest yields of the pyr-
roles, these syntheses could find applications (when optimized) for
the preparation of unusually functionalized pyrroles, as new and
valuable building blocks for advanced technologies, pharmaceuti-
cals, and materials.
and Hydroxamic Acids; Wiley: Chichester, 2008;
p 241; (c) Wang, Z.. In
Comprehensive Organic Name Reactions and Reagents; Wiley: London, 2009;
Part 3.
6. (a) Trofimov, B. A.; Mikhaleva, A. I. N-Vinylpyrroles; Nauka: Novosibirsk, 1984. p
264 (in Russian); (b) Trofimov, B. A. Adv. Heterocycl. Chem. 1990, 51, 177.
7. (a) Schmidt, E. Yu.; Zorina, N. V.; Zaitsev, A. B.; Mikhaleva, A. I.; Vasil’tsov, A. M.;
Audebert, P.; Clavier, G.; Meallet-Renault, R.; Pansu, R. B. Tetrahedron Lett. 2004,
45, 5489; (b) Vasil’tsov, A. M.; Schmidt, E. Yu.; Mikhaleva, A. I.; Zorina, N. V.;
Zaitsev, A. B.; Petrova, O. V.; Krivdin, L. B.; Petrushenko, K. B.; Ushakov, I. A.;
Pozo-Gonzalo, C.; Pomposo, J. A.; Grande, H.-J. Tetrahedron 2005, 61, 7756.
8. (a) Hwu, J. R.; Patel, H. V.; Lin, R. J.; Gray, M. O. J. Org. Chem. 1994, 59, 1577; (b)
Reis, L. V.; Lobo, A. M.; Prabhakar, S.; Duarte, M. P. Eur. J. Org. Chem. 2003, 190;
(c) Galenko, A. V.; Selivanov, S. I.; Lobanov, P. S.; Potekhin, A. A. Chem.
Heterocycl. Compd. 2007, 43, 1124.
9. General procedure for the synthesis of O-vinyloximes 3a–c: A mixture of
ketoxime 1a–c (2 mmol), 1-(2-furyl)-3-phenyl-2-propyn-1-one (2) (392 mg,
2 mmol), and Ph3P (52 mg, 0.2 mmol) in CH2Cl2 (5 mL) was stirred at rt for 7 h
under Ar and then the solution was evaporated. The crystalline products were
ground in Et2O (5 mL) and allowed to stand at À12 ? À8 °C overnight. The
residue was filtered, dried under vacuum, and recrystallized from hexane.
10. General procedure for the synthesis of pyrroles 5a–c: O-2-
(Acyl)vinylketoximes 3a–c (0.5 mmol) were placed into a vial and heated in
an oil bath at 125–130 °C for 2 h. After cooling, the reaction mixture was
diluted with Et2O (5 mL) and separated on Al2O3 using Et2O–hexane (1:3) as
eluent.
Acknowledgment
The work has been carried out under the financial support of
leading scientific schools by the President of the Russian Federa-
tion (Grant NSH 3230-2010.3).
Supplementary data
11. 1H NMR data for (3,5-diphenyl-1H-pyrrol-2-yl)(2-furyl)methanone (6a): dH
(400.1 MHz, CDCl3) 6.48 (dd, 1H, H4furyl 3J = 3.2 Hz, 3J = 1.7 Hz), 7.15 (d, 1H,
,
H4pyrrole
, ,
4J = 2.9 Hz), 7.16 (dd, 1H, Hf3uryl 3J = 1.7 Hz, 4J = 0.8 Hz), 7.35–7.69 (m,
Supplementary data associated with this article can be found, in
11H, Aryl, H5furyl), 8.73 (br s, 1H, NH).
12. Synthesis of (2,4-diphenyl-1H-pyrrol-3-yl)(2-furyl)methanone (7): O-2-
(acyl)vinylketoxime 3a (0.5 mmol) was placed into a vial and heated in an
oil bath at 145–150 °C for 10 min without solvent. After cooling, the reaction
mixture was diluted with Et2O (5 mL) and separated on Al2O3 using Et2O–
hexane (1:3) as eluent.
13. Trofimov, B. A.; Petrova, O. V.; Sobenina, L. N.; Drichkov, V. N.; Mikhaleva, A. I.;
Ushakov, I. A.; Tarasova, O. A.; Kazheva, O. N.; Chekhlov, A. N.; Dyachenko, O. A.
Tetrahedron 2006, 62, 4146.
14. (a) Hansen, P. E. Prog. Nucl. Magn. Reson. Spectrosc. 1981, 14, 175; (b) Pretsch, E.;
Bühlmann, P.; Affolter, C. Structure Determination of Organic Compounds: Tables
of Spectral Data; Springer: Berlin, Heidelberg, New York, 2000. p 422.
15. (a) Sato, S.; Kato, H.; Ohta, M. Bull. Chem. Soc. Jpn 1967, 40, 2936; (b)
Narasimhan, N. S.; Heimgarther, H.; Hansen, H.-J.; Schmid, H. Helv. Chim. Acta
1973, 56, 1351; (c) Filho, P. F. S.; Schuchardt, U. Angew. Chem. 1977, 89, 672; (d)
Trofimov, B. A.; Mikhaleva, A. I. Khim. Geterotsikl. Soed. 1987, 1299 (in Russian);
(e) Palacios, F.; Retana, A. M. O.; Marigorta, E. M.; Santos, J. Eur. J. Org. Chem.
2001, 13, 2401.
16. (a) Trofimov, B. A.; Sobenina, L. N.; Mikhaleva, A. I.; Ushakov, I. A.; Vakul’skaya,
T. I.; Stepanova, Z. V.; Toryashinova, D.-S. D.; Mal’kina, A. G.; Elokhina, V. N.
Synthesis 2003, 1272; (b) Glotova, T. E.; Dvorko, M. Yu.; Ushakov, I. A.;
Chipanina, N. N.; Kazheva, O. N.; Chekhlov, A. N.; Dyachenko, O. A.; Gusarova,
N. K.; Trofimov, B. A. Tetrahedron 2009, 65, 9814.
References and notes
1. (a) Mikhaleva, A. I.; Schmidt, E. Yu.. In Selected Methods for Synthesis and
Modification of Heterocycles; Kartsev, V. G., Ed.; IBS Press: Moscow, 2002; Vol. 1,
pp 334–352; (b) Dembitsky, V. M.; Tolstikov, G. A. Prirodnye Halogenirovannye
Organicheskie Soedineniya; SB RAS: Novosibirsk, 2003 (in Russian); (c) Trofimov,
B. A.; Mikhaleva, A. I.; Schmidt, E. Yu.; Sobenina, L. N. Adv. Heterocycl. Chem.
2010, 99, 209.
2. (a) Yu, A.; Meiser, F.; Caruso, F. Nano Lett. 2004, 4, 177; (b) Yang, R.; Tian, R.;
Yan, J.; Zhang, Y.; Yang, J.; Hou, Q.; Yang, W.; Zhang, C.; Cao, Y. Macromolecules
2005, 38, 244; (c) Qi, X.; Jun, E.; Li, Xu.; Yoon, Y. J.; Yoon, J. J. Org. Chem. 2006, 71,
2881; (d)Skotheim, T. A., Reynolds, J. R., Eds., 3rd ed.Handbook of Conducting
Polymers: Conjugated Polymers: Theory, Synthesis, Properties, and
Characterisation; CRC Press: Boca Raton, London, New York, 2007.
3. (a) Yavari, I.; Anary-Abbasinejad, M.; Nasiri, F.; Djahaniani, H.; Alizadeh, A.;
Bijanzadeh, H. R. Mol. Divers 2005, 9, 209; (b) Minetto, G.; Raveglia, L. F.; Sega,
A.; Taddei, M. Eur. J. Org. Chem. 2005, 5277; (c) Larionov, O. V.; Meijere, A.
Angew. Chem., Int. Ed. 2005, 44, 5664; (d) Lu, Y.; Arndtsen, B. A. Angew. Chem.,
Int. Ed. 2008, 47, 5430; (e) Das, B.; Reddy, G. C.; Balasubramanyam, P.;
Veeranjaneyulu, B. Synthesis 2010, 1625; (f) Wang, H.-Y.; Mueller, D. S.;
Sachwani, R. M.; Londino, H. N.; Anderson, L. L. Org. Lett. 2010, 12, 2290.