Chemistry - A European Journal
10.1002/chem.201604344
COMMUNICATION
Soc. 2014, 136, 646-649; f) Y. Aihara, N. Chatani, J. Am. Chem. Soc.
2014, 136, 898-901; g) K. Chen, B.-F. Shi, Angew. Chem. 2014, 126,
12144-12148; Angew. Chem. Int. Ed. 2014, 53, 11950-11954; h) A.
Deb, S. Bag, R. Kancherla, D. Maiti, J. Am. Chem. Soc. 2014, 136,
13602-13605; i) W. Song, S. Lackner, L. Ackermann, Angew. Chem.
2014, 126, 2510-2513; Angew. Chem. Int. Ed. 2014, 53, 2477-2480; j)
B. M. Monks, E. R. Fruchey, S. P. Cook, Angew. Chem. 2014, 126,
11245-11249; Angew. Chem. Int. Ed. 2014, 53, 11065-11069.
a) R. Parella, S. A. Babu, J. Org. Chem. 2015, 80, 2339-2355; b) B.
Gopalakrishnan, S. A. Babu, R. Padmavathi, Tetrahedron 2015, 71,
8333-8349; c) D. P. Affron, J. A. Bull, Eur. J. Org. Chem. 2016, 139–
149.
A large survey of conditions including many strong acids or
bases at high temperatures resulted mainly in recovered starting
material. Strikingly, pre-ozonolysis of the quinolyl moiety allowed
the cleavage to occur even at room temperature in very high
yield (Scheme 8).
In summary, we have reported herein a new method for
the easy cleavage of the ubiquitous aminoquinoline directing
group in C-H activation chemistry. This protocol employs mild
conditions and enables the preparation of either the carboxylic
acid or the amide derivative, relying on ozonolytic weakening of
the amide function. It is our belief that the conditions herein shall
be deemed useful and widely adopted by the practitioners of C-
H activation at large.
[4]
[5]
a) L. D. Tran, I. Popov, O. Daugulis, J. Am. Chem. Soc. 2012, 134,
18237-18240; For examples using this cleavage protocol, see: b) X.
Chen, Z. Tan, Q. Gui, L. Hu, J. Liu, J. Wu, G. Wang, Chem. Eur. J.
2016, 22, 6218-6222; c) L. Hu, X. Chen, Q. Gui, Z. Tan, G. Zhub, Chem.
Commun., 2016, 52, 6845-6848; d) Q. Gui, X. Chen, L. Hu, D. Wang, J.
Liu, Z. Tana, Adv. Synth. Catal. 2016, 358, 509-514.
Experimental Section
[6]
[7]
a) Y. Feng, G. Chen, Angew. Chem. 2010, 122, 970-973; Angew.
Chem. Int. Ed. 2010, 49, 958-961; b) Y. Feng, Y. Wang, B. Landgraf, S.
Liu, G. Chen, Org. Lett. 2010, 12, 3414-3417.
A stream of ozone is passed through a solution of N-
Quinolylamide (0.2 mmol) in dichloromethane (4 mL) at -78 °C
until the characteristic blue color appears. A stream of oxygen is
passed through until decolorization occurs and the mixture is
quenched with dimethylsulfide (0.05 mL). The mixture was
allowed to warm to RT, stirred for 2 hours and concentrated
under high vacuum to complete dryness. The crude imides were
subjected to the specific hydrolysis or aminolysis conditions
followed by an extraction with DCM (see SI for details and
conditions). Drying with MgSO4 and removal of solvents affords
the desired amides or carboxylic acids.
a) B. T. Y. Li, J. M. White, G. A. Hutton, Aust. J. Chem. 2010, 63, 438–
444; b) J. Dong, F. Wang, J. You, Org. Lett. 2014, 16, 2884−2887; c) W.
R. Gutekunst, P. S. Baran, J. Org. Chem. 2014, 79, 2430−2452.
G. He, S.-Y. Zhang, W. A. Nack, Q. Li, G. Chen, Angew. Chem. 2013,
125, 11330-11334; Angew. Chem. Int. Ed. 2013, 52, 11124-11128.
a) D. P. Affron, O. A. Davis, J. A. Bull, Org. Lett. 2014, 16, 4956−4959;
b) Z. Wang, Y. Kuninobu, M. Kanai, Org. Lett. 2014, 16, 4790−4793; c)
H.-Y. Xiong, D. Cahard, X. Pannecoucke, T. Besset Eur. J. Org. Chem.
2016, 3625–3630.
[8]
[9]
[10] a) W.-W. Sun, P. Cao, R.-Q. Mei, Y. Li, Y.-L. Ma, B. Wu, Org. Lett.
2014, 16, 480−483; b) B. Wang, W. A. Nack, G. He, S.-Y. Zhang, G.
Chen, Chem. Sci., 2014, 5, 3952-3957; c) X. Wu, Y. Zhao, H. Ge,
Chem. Eur. J. 2014, 20, 9530-9533; d) X. Wu, Y. Zhao, G. Zhang, H.
Ge, Angew. Chem. 2014, 126, 3780-3784; Angew. Chem. Int. Ed. 2014,
53, 3706-3710; e) Z. Wang, J. Ni, Y. Kuninobu, M. Kanai, Angew.
Chem. 2014, 126, 3564-3567; Angew. Chem. Int. Ed. 2014, 53, 3496-
3499; f) L. Grigorjeva, O. Daugulis, Org. Lett. 2014, 16, 4684−4687; g)
W. Miura, K. Hirano, M. Miura, Org. Lett. 2015, 17, 4034−4037; h) S.-J.
Zhang, W.-W. Sun, P. Cao, X.-P. Dong, J.-K. Liu, B. Wu, J. Org. Chem.
2016, 81, 956−968; i) Y. Zhou, J. Zhu, B. Li, Y. Zhang, J. Feng, A. Hall,
J. Shi, W. Zhu, Org. Lett. 2016, 18, 380−383.
Acknowledgements
We are grateful to the University of Vienna for continued support
of our research. M.B. was supported by the graduate program
MolTag (Austrian Science Fund FWF W1232). C.A.B.R. was
supported by the Fundacao para a Ciencia e Tecnologia
(SFRH/BPD/100677/2014) and R.C. was supported by the
ERASMUS program. We also thank A. Roller (UVienna) for X-
ray crystallography and M. Galanski and S. Felsinger (UVienna)
for high temperature NMR spectroscopy.
[11] Price for MQ: 77.20 € / g vs. price for AQ: 9.56 € / g (239.00 € / 25 g)
(Sigma Aldrich catalogue on July 18, 2016).
[12] For electrophilic activation of amides, see: a) D. Kaiser, N. Maulide, J.
Org. Chem., 2016, 81, 4421–4428; b) P. Chua, A. B. Charette,
Tetrahedron Lett. 1997, 38, 8499-8502; c) K. L. White, M. Mewald, M.
Movassaghi, J. Org. Chem. 2015, 80, 7403-7411; d) L. Hie, N. F. Fine
Nathel, T. K. Shah, E. L. Baker, X. Hong, Y.-F. Yang, P. Liu, K. N. Houk,
N. K. Garg Nature 2015, 524, 79-83; e) C. Madelaine, V. Valerio, N.
Maulide, Angew. Chem. 2010, 122, 1628-1631; Angew. Chem. Int. Ed.
2010, 49, 1583-1586; For a general overview of amide activation, see:
f) S. Ruider, N. Maulide, Angew. Chem. 2015, 127, 14062-14064;
Angew. Chem. Int. Ed. 2015, 54, 13856-13858.
Keywords: C-H activation • 8-aminoquinoline • directing group •
cleavage • ozonolysis
[1]
a) For a review on C-H activation using bidentate directing groups: G.
Rouquet, N. Chatani, Angew. Chem. 2013, 125, 11942-11959; Angew.
Chem. Int. Ed. 2013, 52, 11726-11743; b) for
a highlight on 8-
Aminoquinoline directing group: M. Corbet, F. De Campo, Angew.
Chem. 2013, 125, 10080-10082; Angew. Chem. Int. Ed. 2013, 52,
9896-9898.
[13] a) B. T. Kalakutskii, M. A. Kosareva, N. D. Rus’yanova, N. V.
Malysheva, Zh. Prikl. Khimii, 1977, 50, 2121-2122; b) C. O'Murchu,
Synthesis, 1989, 11, 880-82.
[2]
[3]
V. G. Zaitsev, D. Shabashov, O. Daugulis, J. Am. Chem. Soc. 2005,
127, 13154-13155.
[14] a) C. Wang, Y. Yang, D. Qin, Z. He, J. You, J. Org. Chem. 2015, 80,
8424−8429; b) X. Wu, K. Yang, Y. Zhao, H. Sun, G. Li, H. Ge, Nat.
Commun. 2015, 6:6462.
For selected publications utilizing AQ-directing group, see: a) D.
Shabashov, O. Daugulis, J. Am. Chem. Soc. 2010, 132, 3965-3972; b)
Y. Aihara, N. Chatani, J. Am. Chem. Soc. 2013, 135, 5308-5311; c) R.
Shang, L. Ilies, A. Matsumoto, E. Nakamura, J. Am. Chem. Soc. 2013,
135, 6030-6032; d) G. Shan, X. Yang, Y. Zong, Y. Rao, Angew. Chem.
2013, 125, 13851-13855; Angew. Chem. Int. Ed. 2013, 52, 13606-
13610; e) T. Matsubara, S. Asako, L. Ilies, R. Nakamura, J. Am. Chem.
[15] For a review on biological activity of DHAA, see: González, M. A. Nat.
Prod. Rep. 2015, 32, 684-704.
[16] a) D.-H. Wang, M. Wasa, R. Giri, J.-Q. Yu, J. Am. Chem. Soc. 2008,
130, 7190-7191; b) M. E. Farmer, B. N. Laforteza, J.-Q. Yu, Bioorg.
Med. Chem. 2014, 22, 4445–4452.
This article is protected by copyright. All rights reserved