10.1002/adsc.201800845
Advanced Synthesis & Catalysis
guignon, Tetrahedron Lett. 2004, 45, 6343–6348; d) Z.
Cai, Y. Guo, S. Yang, Q. Peng, H. Luo, Z. Liu, G.
Zhang, Y. Liu, D. Zhang, Chem. Mater. 2013, 25, 471–
478; e) C. C. Cosner, J. T. Markiewicz, P. Bourbon, C.
J. Mariani, O. Wiest, M. Rujoi, A. I. Rosenbaum, A. Y.
Huang, F. R. Maxfield, P. Helquist, J. Med. Chem.
2009, 52, 6494–6498; f) M. M. Alam, A. Husain, S. M.
Hasan Suruchi, Suruchi, T. Anwer, Eur. J. Med. Chem.
2009, 44, 2636–2642; g) A. Husain, M. Alam Mumtaz,
N. Siddiqui, J. Serb. Chem. Soc. 2009, 74, 103–115; h)
A. Husain, M. S. Y. Khan, S. M. Hasan, M. M. Alam,
Eur. J. Med. Chem. 2005, 40, 1394–1404; i) A. Husain,
M. M. Alam, M. Shaharyar, S. Lal, J. Enzyme Inhib.
Med. Chem. 2010, 25, 54–61; j) L. Fina, D. G. Igor, B.
Blanka, Arch. Pharm. 1990, 323, 901–904; k) S.
Hakvag, E. Fjaervik, G. Klinkenberg, S. E. Borgos, K.
Josefsen, T. Ellingsen, S. Zotchev, Mar. Drugs 2009, 7,
576–588; l) S. Yada, Y. Wang, Y. Zou, K. Nagasaki, K.
Hosokawa, I. Osaka, R. Arakawa, K. Enomoto, Mar.
Biotechnol. 2008, 10, 128–132.
Scheme 4. Proposed mechanism.
In conclusion, an efficient base-promoted cascade
approach to substituted 4-pyrrolin-2-ones from readi-
ly available pyrroles under metal-free conditions has
been developed. A novel cascade aerobic oxida-
tion/semipinacol rearrangement was involved in this
transformation. This protocol employed 1 atm of
molecular oxygen as the ideal oxidant and could pro-
ceed well at room temperature, making this method
sustainable and environmentally friendly.
[2] a) H. A. Abd El-Nabi, Tetrahedron 2000, 56, 3013–
3020; b) B. Metten, M. Kostermans, G. Van Baelen, M.
Smet, W. Dehaen, Tetrahedron 2006, 62, 6018–6028.
[3] Q. Yuan, D. Liu, W. Zhang, Org. Lett. 2017, 19, 1144–
1147.
[4] For a review: a) G. Martelli, M. Orena, S. Rinaldi,
Curr. Org. Chem. 2014, 18, 1373–1481; for selected
recent examples: b) S. Fustero, B. Fernández, P. Bello,
C. Pozo, S. Arimitsu, G. B. Hammond, Org. Lett. 2007,
9, 4251–4253; c) L. Yang, D.-X. Wang, Z.-T. Huang,
M.-X. Wang, J. Am. Chem. Soc. 2009, 131, 10390–
10391; d) Q. Pei, B. Cui, W. Han, Z. Wu, X. Zhang, W.
Yuan Tetrahedron 2014, 70, 4595–4601; e) X. Wang,
C. Zhang, H. Tu, A. Zhang, Eur. J. Org. Chem. 2016,
5243–5247; f) K.-Z. Li, J.-S. You, J. Org. Chem. 2016,
81, 2327–2339; g) P. Gao, J. Wang, Z. Bai, M. Fan, D.
Yang, Z. Guan, Org. Lett. 2018, 20, 3627–3630.
Experimental Section
A mixture of pyrroles 1 (0.5 mmol) and NaOtBu (0.6
mmol, 1.2 equiv.) in DMSO (2 mL) was stirred in room
o
temperature (25 C) under an atmosphere of O2 for 4 h
(monitored by TLC). Then H2O was added and the result-
ant was extracted with EtOAc (3 10 mL). The combined
EtOAc extracts were dried over Na2SO4 and concentrated.
Then solvent was evaporated and the residue was purified
by silica gel flash chromatography (EtOAc/PE: 1/8) to give
4-pyrrolin-2-ones 2.
[5] For recent reviews: a) S. P. Roche, J. A. Porco, Jr.,
Angew. Chem. Int. Ed. 2011, 50, 4068–4093; b) T. J.
Donohoe, R. D. C. Pullin, Chem. Commun. 2012, 48,
11924–11938; c) Q. Ding, X. Zhou, R. Fan, Org. Bio-
mol. Chem. 2014, 12, 4807–4815; d) C.-X. Zhuo, C.
Zheng, S.-L. You, Acc. Chem. Res. 2014, 47, 2558–
2573; e) X.-W. Liang, C. Zheng, S.-L. You, Chem. Eur.
J. 2016, 22, 11918–11933; f) W. Sun, G. Li, L. Hong,
R. Wang, Org. Biomol. Chem. 2016, 14, 2164–2176; g)
C. Zheng, S.-L. You, Chem. 2016, 1, 830–857.
Acknowledgements
We gratefully acknowledge the financial support of Scientific
Research Foundation of Xiamen Huaxia University (P1003),
Outstanding Youth Scientific Research Cultivation Plan in Fujian
Province University (2017146), Fujian Education and Scientific
Research Project for Young and Middle-aged Teachers
(JAT160638, JAT160639, JAT170827 and JAT170819) and the
Research Program for Xiamen Overseas Students 2016 funded by
Xiamen Municipal Human Resources and Social Security Bureau.
We thank Professor Xiuling Cui from Huaqiao University for
compound characterization.
[6] a) T. J. Donohoe, R. E. Thomas, Chem. Record 2007, 7,
180–190; b) B. S. Gourlay, J. H. Ryan, J. A. Smith,
Beilstein J. Org. Chem. 2008, 4:3; c) G. Journot, C.
Letondor, R. Neier, H. Stoeckli‐Evans, D. Savoia, A.
Gualandi, Chem. Eur. J., 2010, 16, 4224–4230; d) H. T.
You, A. C. Grosse, J. K. Howard, C. J. T. Hyland, J.
Just, P. P. Molesworth, J. A. Smith, Org. Biomol. Chem.
2011, 9, 3948–3953; e) W. Maupillier, G. Journot, H. S.
Evans, R. Neier, Eur. J. Org. Chem. 2017, 6023–6037;
f) K. J. Rihak, A. C. Bissember, J. A. Smith, Tetrahe-
dron 2018, 74, 1167–1174; for other recent dearomati-
zation of pyrroles, see: g) Z.-P. Yang, C.-X. Zhuo, S.-L.
You, Adv. Synth. Catal. 2014, 356, 1731– 1734; h) C.-
References
[1] a) Y. Ali, M. Sharwar Alan, Y. Ali, S. M. Alama, H.
Hamida, A. Hussain, Orient. J. Chem. 2014, 30, 1–16;
b) T. Aysha, S. Lunak Jr., A. Lycka, J. Vynuchal, Z.
Elias, A. Ruzicka, Z. Padelkova, R. Hrdina, Dyes Pig-
ments 2013, 98, 530–539; c) M. Bourotte, M. Schmitt,
A. Follenius-Wund, C. Pigault, J. Haiech, J.-J. Bour-
4
This article is protected by copyright. All rights reserved.