10.1002/chem.202101824
Chemistry - A European Journal
FULL PAPER
[3]
[4]
a) M. I. Calaza, C. Cativiela, Eur. J. Org. Chem. 2008, 3427–3448; b) J.
Cossy, O. Mirguet, D. G. Pardo, Synlett 2001, 1575–1577.
rotational entropy. Unfortunately, the optimized condition for the
eight-membered ring formation was ineffective, and the substrate
was recovered completely. We once more attempted to utilize the
C-dtbm ligand[12] and found that oxazonine 6 was isolated with
34% yield after full conversion (Scheme 5). The molecular
structure was unambiguously confirmed through X-ray
crystallographic analysis (Figure 2).[17] The isolation of 4 and 6
clearly demonstrate the feasibility of the semihollow-shaped C-
dtbm ligand for direct end-to-end eight-membered ring formation
and arylative nine-membered ring formation.
a) C. R. M. Souza, W. P. Bezerra, J. T. Souto, Mar. Drugs 2020, 18, 1–
17; b) M. F. Raub, J. H. Cardellina, J. G. Schwede, Phytochemistry 1987,
26, 619–620; c) C. G. L. Veale, M. T. Davies-Coleman, The Alkaloids:
Chemistry and Biology 2014, 73, 1–64.
[5]
a) Hussain, S. K. Yousuf, D. Mukherjee, RSC Adv. 2014, 4, 43241–
43257; b) F. A. Macias, R. M. Varela, A. Torres, J. M. G. Molino, F. R.
Fronczek, Tetrahedron Lett. 1993, 34, 1999–2002; c) B. Hoefgen, M.
Decker, P. Mohr, A. M. Schramm, S. A. F. Rostom, H. El-Subbagh, P. M.
Schweikert, D. R. Rudolf, M. U. Kassack, J. Lehmann, J. Med. Chem.
2006, 49, 760–769; d) K. R. Romines, K. D. Watenpaugh, P. K. Tomich,
W. J. Howe, J. K. Morris, K. D. Lovasz, A. M. Mulichak, B. C. Finzelj, J.
C. Lynn, M.-M.Horng, F. J. Schwende, M. J. Ruwart, G. L. Zipp, K.-T.
Chong, L. A. Dolak, L. N. Toth, G. M. Howard, B. D. Rush, Karen F.
Wilkinson, P. L. Possert, R. J. Dalga, R. R. Hinshaw. J. Med. Chem. 1995,
38, 1884–1891.
O
(C-dtbm)AuCl
5 mol%
[6]
a) W. R. J. D. Galloway, A. Isidro-Llobet, D. R. Spring, Nat. Commun.
2010, 1, 80; b) L. Li, Z.-L. Li, F. L. Wang, Z. Guo, Y. F. Cheng, N. Wang,
X. W. Dong, C. Fang, J. Liu, C. Hou, B. Tan, X.-Y. Liu, Nat. Commun.
2016, 7, 13852; c) A. Noren-Muller, I. Reis-Correa Jr., H. Prinz, C.
Rosenbaum, K. Saxena, H. J. Schwalbe, D. Vestweber, G. Cagna, S.
Schunk, O. Schwarz, H. Schiewe, H. Waldmann, Proc. Natl. Acad. Sci.
2006, 103, 10606–10611; d) M. Kaisera, S. Wetzel, K. Kumar, H.
Waldmann, Cell. Mol. Life Sci. 2008, 65, 1186–1201; e) S. Wetzel, R. S.
Bon, K. Kumar, H. Waldmann, Angew. Chem. Int. Ed. 2011, 50, 10800–
10826; Angew. Chem. 2011, 123, 10990–11018; f) H. Ohno, S. Inuki,
Org. Biomol. Chem. 2021, 16, 3551–3568; g) G. Karageorgis, D. J. Foley,
L. Laraia, H. Waldmann, Nat. Chem. 2020, 12, 227–235; h) G. S.
a) R. L. Reyes, T. Iwai, M. Sawamura, Chem. Rev., in press (DOI:
10.1021/acs.chemrev.0c00793); b) J. R. Donald, W. P. Unsworth, Chem.
Eur. J. 2017, 23, 8780–8799; c) A. K. Clarke, W. P. Unsworth, Chem. Sci.
2020, 11, 2876–2881; d) C. Galli, L. Mandolini, Eur. J. Org. Chem. 2000,
3117–3125; e) C. Galli, L. Mandolini, Acc. Chem. Res. 1981, 14, 95–102;
f) T. Huber, R. E. Wildermuth, T. Magauer, Chem. Eur. J. 2018, 24,
12107–12120.
10 mol% AgSbF6
9
N
O
CH2Cl2, RT, 5 min
Ns
N
H
N
1 mM
N3
Ns
34%
5
6
Scheme 5: Construction of the indole-fused oxazonine using the semihollow-
shaped C-dtbm ligand.
Conclusion
In summary, we have shown that indole-fused benzannulated
eight- and nine-membered rings can be obtained through gold-
catalyzed cascade cyclizations of azido-alkynes, when arenes are
used as internal nucleophiles for trapping the intermediary α-
imino gold(I)-carbenes. Notably, the ease of ring closure was
significantly affected by high dilution conditions, the polarization
of the gold(I)-carbene, the arene moiety, and the N-protecting
group.[22] Additionally, we found that the semihollow-shaped C-
dtbm ligand is indispensable for the alkoxylative eight-membered-
and arylative nine-membered ring formation. The developed
method can enter biologically relevant chemical space and
created a library of a promising class of indole- and bisindole-
fused medium-sized rings, potentially useful for medicinal
applications.
[7]
[8]
[9]
a) L.-W. Ye, X.-Q. Zhu, R. L. Sahani, Y. Xu, P.-C. Qian, R.-S. Liu, Chem.
Rev., in press (DOI: 10.1021/acs.chemrev.0c00348); b) X. Zhao,
Rudolph, A. M. Asiri, A. S. K. Hashmi, Front. Chem. Sci. Eng. 2020, 14,
317–349; c) F. L. Hong, L.-W. Ye, Front. Chem. Sci. Eng. 2020, 14, 317–
349; d) E. Aguilar, J. Santamaria, Org. Chem. Front. 2019, 6, 1513–1540;
e) X. Tian, L. Song, A. S. K. Hashmi, Chem. Eur. J. 2020, 26, 3197–3204.
D. J Gorin, N. R. Davis, F. D. Toste, J. Am. Chem. Soc. 2005, 127,
11260–11261.
[10] a) B. Lu, Y. Luo, L. Liu, L. Ye, Y. Wang, L. Zhang, Angew. Chem. Int. Ed.
2011, 50, 8358–8362; Angew. Chem. 2011, 123, 8508–8512; b) A.
Wetzel, F. Gagosz, Angew. Chem. Int. Ed. 2011, 50, 7354–7358; Angew.
Chem. 2011, 123, 7492–7496; c) J. Cai, B. Wu, G. Rong, C. Zhang, L.
Qui, X. Xu, Org. Lett. 2018, 20, 2733−2736.
Acknowledgements
This work was supported by the JSPS KAKENHI (JP17H03971
and 20K06938), AMED (Grant Number JP20am0101092j and
JP20gm1010007), and the Tokyo Biochemical Research
Foundation (TBRF).
[11] For our recent works on α-imino gold(I) carbene chemistry, see: a) Y.
Tokimizu, S. Oishi, N. Fujii, H. Ohno, Org. Lett. 2014, 16, 3138–3141; b)
Y. Kawada, S. Ohmura, M. Kobayashi, W. Nojo, M. Kondo, Y. Matsuda,
J. Matsuoka, S. Inuki, S. Oishi, C. Wang, T. Saito, M. Uchiyama, T.
Suzuki, H. Ohno, Chem. Sci. 2018, 9, 8416–8425; c) J. Matsuoka, Y,
Matsuda, Y. Kawada, S. Oishi, H. Ohno, Angew. Chem. Int. Ed. 2017,
56, 7444−7448; Angew. Chem. 2017, 129, 7552–7556; d) J. Matsuoka,
S. Inuki, Y. Matsuda, Y. Miyamoto, M. Otani, M. Oka, S. Oishi, H. Ohno,
Chem. Eur. J. 2020, 26, 11150–11157.
Keywords: arylation • medium-sized rings • gold-catalysis •
heterocycles • α-imino gold(I)-carbenes
[1]
a) M. E. Welsch, S. A. Snyder, B. R. Stockwell, Curr. Opin. Chem. Biol.
2010, 14, 347–361; b) F. R. de Sá Alves, E. J. Barreiro, C. A. M. Fraga,
Mini-Rev. Med. Chem. 2009, 9, 782–793; c) D. A. Horton, G. T. Bourne,
M. L. Smythe, Chem. Rev. 2003, 103, 893−930; d) J. F. Austin, D. W. C.
MacMillan, J. Am. Chem. Soc. 2002, 124, 1172–1173; e) M. Bandini, A.
Eichholzer, Angew. Chem. Int. Ed. 2009, 48, 9608–9644; Angew. Chem.
2009, 121, 9786–9824; f) V. Sharma, P. Kumar, D. Pathak, J.
Heterocyclic Chem. 2010, 47, 491–502.
[12] a) T. Iwai, H. Okochi, H. Ito, M. Sawamura, Angew. Chem. Int. Ed. 2013,
52, 4239–4242; Angew. Chem. 2013, 125, 4333–4336; b) T. Iwai, M.
Ueno, H. Okochi, M. Sawamura, Adv. Synth. Catal. 2018, 360, 670–675;
c) A. Ochida, H. Ito, M. Sawamura, J. Am. Chem. Soc. 2006, 128,
16486–16487.
[13] a) J. Schießl, J. Schulmeister, A. Doppiu, E. Wörner, M. Rudolph, R.
Karch, A. S. K. Hashmi, Adv. Synth. Catal. 2018, 360, 2493–2502; b) J.
Schießl, J. Schulmeister, A. Doppiu, E. Wörner, M. Rudolph, R. Karch,
A. S. K. Hashmi, Adv. Synth. Catal. 2018, 360, 3949–3959; c) Z. Lu, J.
Han, O. E. Okoromoba, N. Shimizu, H. Amii, C. F. Tormena, G. B.
[2]
a) A. Okabe, S. Harada, T. Takeda, A. Nishida, Eur. J. Org. Chem. 2019,
3916–3920; b) L. M. Rice, E. Hertz, M. E. Freed, J. Med. Chem. 1964, 7,
313–319; c) B. L. Baxter, M. I. Gluckman, Nature 1969, 223, 750–752.
5
This article is protected by copyright. All rights reserved.