10.1002/anie.201914876
Angewandte Chemie International Edition
COMMUNICATION
308, Part 2, 131–190. g) J. Wencel-Delord, A. Panossian, F. R. Leroux,
F. Colobert, Chem. Soc. Rev. 2015, 44, 3418–3430. h) Y.-B. Wang, B.
Tan, Acc. Chem. Res. 2018, 51, 534–547.
CuBOX complex followed by oxidative addition may also be
envisioned.
In depth further mechanistic studies are needed to elucidate this
[2]
[3]
I. Takahashi, Y. Suzuki, O. Kitagawa, Org. Prep. Proc. Int. 2014, 46, 1–
23.
catalytic cycle as well as the stereoselectivity.
NH2
O
C
Evidenced by
ESI analysis &
X-ray
a) P. W. Glunz, Bioorg. Med. Chem. Lett. 2018, 28, 53–60. b) S. T.
Toenjes, J. L. Gustafson, Future Med. Chem. 2018, 10, 409–422. c) S.
R. LaPlante, L. D. Fader, K. R. Fandrick, D. R. Fandrick, O. Hucke, R.
Kemper, S. P. F. Miller, P. J. Edwards, J. Med. Chem. 2011, 54, 7005–
7022. d) G. Beutner, R. Carrasquillo, P. Geng, Y. Hsiao, E. C. Huang,
J. Janey, K. Katipally, S. Kolotuchin, T. La Porte, A. Lee, et al., Org.
Lett. 2018, 20, 3736–3740. e) J. Chandrasekhar, R. Dick, J. Van
Veldhuizen, D. Koditek, E.-I. Lepist, M. E. McGrath, L. Patel, G. Phillips,
K. Sedillo, J. R. Somoza, et al., J. Med. Chem. 2018, 61, 6858–6868. f)
T. Sugane, T. Tobe, W. Hamaguchi, I. Shimada, K. Maeno, J. Miyata,
T. Suzuki, T. Kimizuka, S. Sakamoto, S. Tsukamoto, J. Med. Chem.
2013, 56, 5744–5756. g) J. Wang, W. Zeng, S. Li, L. Shen, Z. Gu, Y.
Zhang, J. Li, S. Chen, X. Jia, ACS Med. Chem. Lett. 2017, 8, 299–303.
h) S. H. Watterson, G. V. De Lucca, Q. Shi, C. M. Langevine, Q. Liu, D.
G. Batt, M. Beaudoin Bertrand, H. Gong, J. Dai, S. Yip, et al., J. Med.
Chem. 2016, 59, 9173–9200. i) S. R. Selness, R. V. Devraj, B.
Devadas, J. K. Walker, T. L. Boehm, R. C. Durley, H. Shieh, L. Xing, P.
V. Rucker, K. D. Jerome, et al., Bioorg. Med. Chem. Lett. 2011, 21,
4066–4071. j) A. L. Leivers, M. Tallant, J. B. Shotwell, S. Dickerson, M.
R. Leivers, O. B. McDonald, J. Gobel, K. L. Creech, S. L. Strum, A.
Mathis, et al., J. Med. Chem. 2014, 57, 2091–2106. k) F. Hasegawa, K.
Kawamura, H. Tsuchikawa, M. Murata, Bioorg. Med. Chem. 2017, 25,
4506–4511.
R2
*
X
I
N
N
N
R1
Mes
Cu
N
*
A
NH2
C
O
C
R2
R2
*
N
O
N
S
H2N
N
N
N
N
N
N
Cu
CuIII
CuIII
N
*
*
I
R1
R1
S
I
R1
B
CONH2
B’
Evidenced by
ESI analysis
(CuBOX-Ar)
HN
R2
2A
Evidenced by ESI
analysis from a
stoechiometric
reaction
(after addition of
2A and Et3N to B )
NH2
C
NH2
C
R2
R2
O
O
N
N
CuIII
CuIII
*
*
N
R1
N
I
R1
N
H
N
D
C
Et3N+I-
Et3
N
Figure 6. Proposed catalytic cycle.
In conclusion, we report herein the first example of
atroposelective metal catalyzed N-arylation delivering N-C
axially chiral compounds. Use of various hypervalent iodine
coupling partners allows this Cu-catalyzed hindered coupling to
occur at room temperature, thus warranting excellent
stereoselectivity. This protocol delivers efficiently original N-C
[4]
[5]
A. Mannschreck, E. von Angerer, J. Chem. Educ. 2009, 86, 1054.
For selected examples see: a) T. Mino, D. Yamaguchi, C. Masuda, J.
Youda, T. Ebisawa, Y. Yoshida, M. Sakamoto, Org. Biomol. Chem.
2019, 17, 1455–1465. b) Y. Kikuchi, C. Nakamura, M. Matsuoka, R.
Asami, O. Kitagawa, J. Org. Chem. 2019, 84, 8112–8120. c) T. Mino,
Y. Tanaka, T. Yabusaki, D. Okumura, M. Sakamoto, T. Fujita,
Tetrahedron: Asymmetry 2003, 14, 2503–2506. d) T. Mino, H. Yamada,
S. Komatsu, M. Kasai, M. Sakamoto, T. Fujita, Eur. J. Org. Chem.
2011, 2011, 4540–4542. e) T. Mino, M. Asakawa, Y. Shima, H.
Yamada, F. Yagishita, M. Sakamoto, Tetrahedron 2015, 71, 5985–
5993. f) T. Mino, K. Nishikawa, M. Asano, Y. Shima, T. Ebisawa, Y.
Yoshida, M. Sakamoto, Org. Biomol. Chem. 2016, 14, 7509–7519.
a) B. E. Dial, R. D. Rasberry, B. N. Bullock, M. D. Smith, P. J. Pellechia,
S. Profeta, K. D. Shimizu, Org. Lett. 2011, 13, 244–247. b) B. E. Dial,
P. J. Pellechia, M. D. Smith, K. D. Shimizu, J. Am. Chem. Soc. 2012,
134, 3675–3678. c) Y. Suzuki, M. Kageyama, R. Morisawa, Y. Dobashi,
H. Hasegawa, S. Yokojima, O. Kitagawa, Chem. Commun. 2015, 51,
11229–11232.
atropisomeric
compounds,
molecules
of
interest
for
pharmaceutical industry. In addition, preliminary mechanistic
studies show exceptional non-linear amplification and very fast
initial rate of the reaction, thus further illustrating the uncommon
features of this original transformation.
Acknowledgements
[6]
We thank the CNRS (Centre National de la Recherche
Scientifique), the “Ministere de l’Education Nationale et de la
Recherche“) France for financial support. J. F. is very grateful to
the “Ministere de l’Education Nationale et de la Recherche“,
France for a doctoral grant. We are also very grateful to Dr.
Lydia Karmazin and Dr. Corinne Bailly for single crystal X-ray
diffraction analysis. We thank very warmly Dr. Antonis Messinis
and Prof. Lutz Ackermann (University of Göttingen) for their help
in HESI analysis as well as Dr. Christopher Golz (University of
Göttingen) for the X-ray diffraction analysis.
[7]
[8]
For selected examples see: a) M. Hirai, S. Terada, H. Yoshida, K.
Ebine, T. Hirata, O. Kitagawa, Org. Lett. 2016, 18, 5700–5703. b) J.
Clayden, H. Turner, Tetrahedron Letters 2009, 50, 3216–3219. c) M. E.
Diener, A. J. Metrano, S. Kusano, S. J. Miller, J. Am. Chem. Soc. 2015,
137, 12369–12377.
For selected examples see: a) S. Shirakawa, K. Liu, K. Maruoka, J. Am.
Chem. Soc. 2012, 134, 916–919. b) T. Hirata, I. Takahashi, Y. Suzuki,
H. Yoshida, H. Hasegawa, O. Kitagawa, J. Org. Chem. 2016, 81, 318–
323. c) O. Kitagawa, M. Takahashi, M. Yoshikawa, T. Taguchi, J. Am.
Chem. Soc. 2005, 127, 3676–3677. d) F. Hasegawa, Y. Yasukawa, K.
Kawamura, H. Tsuchikawa, M. Murata, Asian J. Org. Chem. 2018, 7,
1648–1653. e) O. Kitagawa, M. Yoshikawa, H. Tanabe, T. Morita, M.
Takahashi, Y. Dobashi, T. Taguchi, J. Am. Chem. Soc. 2006, 128,
12923–12931. f) J. Terauchi, D. P. Curran, Tetrahedron: Asymmetry
2003, 14, 587–592. g) S.-L. Li, C. Yang, Q. Wu, H.-L. Zheng, X. Li, J.-
P. Cheng, J. Am. Chem. Soc. 2018, 140, 12836–12843. h) X. Fan, X.
Zhang, C. Li, Z. Gu, ACS Catal. 2019, 9, 2286–2291.
Keywords: N-C axial chirality • atropisomerism • asymmetric C-
N coupling • hypervalent iodine
[1]
a) J. E. Smyth, N. M. Butler, P. A. Keller, Nat. Prod. Rep. 2015, 32,
1562–1583. b) G. Bringmann, A. J. Price Mortimer, P. A. Keller, M. J.
Gresser, J. Garner, M. Breuning, Angew. Chem. Int. Ed. 2005, 44,
5384–5427. c) G. Bringmann, T. Gulder, T. A. M. Gulder, M. Breuning,
Chem. Rev. 2011, 111, 563–639. d) E. Kumarasamy, R. Raghunathan,
M. P. Sibi, J. Sivaguru, Chem. Rev. 2015, 115, 11239–11300. e) P.
Renzi, Org. Biomol. Chem. 2017, 15, 4506–4516. f) P. Loxq, E.
Manoury, R. Poli, E. Deydier, A. Labande, Coord. Chem. Rev. 2016,
[9]
K. Tanaka, K. Takeishi, K. Noguchi, J. Am. Chem. Soc. 2006, 128,
4586–4587.
This article is protected by copyright. All rights reserved.