COMMUNICATIONS
Concise Synthesis of 4-Acylquinolines via Intramolecular Cyclization
References
[1] a) O. Afzal, S. Kumar, M. R. Haider, M. R. Ali, R.
Kumar, M. Jaggi, S. Bawa, Eur. J. Med. Chem. 2015, 97,
871–910; b) B. Gryzlo, K. Kulig, Mini-Rev. Med. Chem.
2014, 14, 332–344; c) A. P. Gorka, A. Dios, P. D. Roepe,
J. Med. Chem. 2013, 56, 5231–5246; d) P. M. Orhan, B.
Tekiner, S. Suzen, Mini-Rev. Med. Chem. 2013, 13, 365–
372; e) R. I. Balderas, B. P. Gonzalez, A. Garcia, B. K.
Banik, G. Rivera, Curr. Med. Chem. 2012, 19, 4377–
4398; f) V. R. Solomon, H. Lee, Curr. Med. Chem.
2011, 18, 1488–1508; g) K. Kaur, M. Jain, R. P. Reddy,
R. Jain, Eur. J. Med. Chem. 2010, 45, 3245–3264;
h) L. M. Bedoya, M. J. Abad, E. Calonge, L. A. Saave-
dra, C. M. Gutierrez, V. V. Kouznetsov, J. Alcami, P.
Bermejo, Antiviral Res. 2010, 87, 338–344; i) J. P. Mi-
chael, Nat. Prod. Rep. 2008, 25, 166–187.
Scheme 3. Reaction on a larger scale.
carbamoyl radical A generated in KO-t-Bu/DMF ab-
stracts the a-hydrogen of 1a. The resulting allyl radi-
cal C undergoes a rearrangement to give the radical
D. After the abstraction of a hydrogen atom from
DMF, an enamine intermediate E is generated. The
subsequent intramolecular addition and the dehydra-
tion give the final product 2a.
The reaction was also carried out on a larger scale
(5 mmol). The product 2a was still obtained in a good
yield (Scheme 3).
In summary, we have developed an intramolecular
cyclization of allylamines and ketones in the presence
of KO-t-Bu/DMF. A series of 4-arylquinolines was
prepared in good yields. The reaction could be accom-
plished at room temperature using only a substoichio-
metric amount of KO-t-Bu. This finding represents
a new strategy for the synthesis of quinoline deriva-
tives.
[2] For reviews on quinoline synthesis, see: a) R. I. Khus-
nutdinov, A. R. Bayguzina, U. M. Dzhemilev, J. Orga-
nomet. Chem. 2014, 768, 75–114; b) S. M. Prajapati,
K. D. Patel, R. H. Vekariya, S. N. Panchal, H. D. Patel,
RSC Adv. 2014, 4, 24463–24476; c) S. Madapa, Z. Tusi,
S. Batra, Curr. Org. Chem. 2008, 12, 1116–1183;
d) V. V. Kouznetsov, L. Y. V. Mendez, C. M. M. Gomez,
Curr. Org. Chem. 2005, 9, 141–161.
[3] a) H. Saggadi, D. Luart, N. Thiebault, I. Polaert, L.
Estel, C. Len, Catal. Commun. 2014, 44, 15–18;
b) R. H. F. Manske, M. Kulka, Org. React. 1953, 7, 59–
98.
[4] a) Y.-C. Wu, L. Liu, H.-J. Li, D. Wang, Y.-J. Chen, J.
Org. Chem. 2006, 71, 6592–6595; b) S. A. Yamashkin,
E. A. Oreshkina, Chem. Heterocycl. Compd. 2006, 42,
701–718; c) F. W. Bergstrom, Chem. Rev. 1944, 35, 77–
277.
[5] a) M. C. JosØ, P. M. Elena, S. Abdelouahid, C. C.
María, S. Elena, Chem. Rev. 2009, 109, 2652–2671;
b) R. M. Brian, L. M. Benjamin, Org. Lett. 2003, 5,
4257–4259; c) C.-C. Cheng, S.-J. Yan, Org. React. 1982,
28, 37–201.
Experimental Section
Typical Procedure for Intramolecular Cyclization
A solution of 1a (47.4 mg, 0.2 mmol), KO-t-Bu (11.5 mg,
0.10 mmol) in DMF (2 mL) was stirred at room temperature
under an argon atmosphere for 5 h. After completion of the
reaction as shown by TLC, the solvent was removed under
vacuum. The crude product was purified by flash chroma-
tography to give 2a as a white solid; yield: 35.5 mg (81%);
[6] a) J. N. Sangshetti, A. S. Zambare, I. Gonjari, D. B.
Shinde, Mini-Rev. Med. Chem. 2014, 14, 225–250; b) D.
Goek, R. Kasimogullari, M. Cengiz, S. Mert, J. Hetero-
cycl. Chem. 2014, 51, 224–232; c) N. P. Buu-Hoi, R.
Royer, N. D. Xuong, P. Jacquignon, J. Org. Chem. 1953,
18, 1209–1224.
1
mp 87–898C. H NMR (400 MHz, CDCl3): d=8.88 (s, 1H),
8.14 (d, J=8.4 Hz, 1H), 7.65 (t, J=7.5 Hz, 1H), 7.58–7.51
(m, 2H), 7.51–7.45 (m, 2H), 7.42 (d, J=6.8 Hz, 1H), 7.31–
7.24 (m, 2H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3):
d=152.68, 146.88, 146.29, 136.89, 129.36, 129.26, 128.62,
128.22, 128.07, 127.92, 127.57, 126.45, 125.91, 17.64; HR-MS
(ESI); m/z=220.1127, calculated for C16H14N (M+H)+:
220.1121.
[7] a) J. C. Sloop, J. Phys. Org. Chem. 2009, 22, 110–117;
b) J.-J. Li, E. J. Corey, Name Reactions in Heterocyclic
Chemistry, Jophn Wiley Sons, Inc., 2005, pp 390–397.
[8] For selected recent examples of quinolines synthesis
through transition metal catalysis, see: a) Y. Wang, X.
Su, C. Chen, Synlett 2013, 24, 2619–2623; b) Y. Wang,
C. Chen, J. Peng, M. Li, Angew. Chem. 2013, 125,
5431–5435; Angew. Chem. Int. Ed. 2013, 52, 5323–5327;
c) Y. Wang, C. Chen, S. Zhang, Z.-B. Lou, X. Su, L.-R.
Wen, M. Li, Org. Lett. 2013, 15, 4794–4797; d) R.-L.
Yan, X.-X. Liu, C.-M. Pan, X.-Q. Zhou, X.-N. Li, X.
Kang, G.-S. Huang, Org. Lett. 2013, 15, 4876–4879;
e) Y. Matsubara, S. Hirakawa, Y. Yamaguchi, Z. Yoshi-
da, Angew. Chem. 2011, 123, 7812–7815; Angew. Chem.
Int. Ed. 2011, 50, 7670–7673; f) L. Zhang, L.-Y. Zheng,
B. Guo, R.-M. Hua, J. Org. Chem. 2014, 79, 11541–
11548.
Acknowledgements
We thank the National Natural Science Foundation of China
(Nos. 21202208, 21172270, 21472248), Guangdong Engineer-
ing Research Center of Chiral Drugs, and Major Scientific
and Technological Project of Guangdong Province (No.
2011A080300001) for the financial support of this study.
Adv. Synth. Catal. 2015, 357, 3474 – 3478
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3477