Organic & Biomolecular Chemistry
Please do not adjust margins
Page 4 of 6
ARTICLE
Journal Name
cyclohexadienyl radical V. Oxidation of radical V by Ir(IV)
regenerates Ir(III) and gives the cationic intermediate VI. Finally,
proton abstraction assisted by the base yields 6-alkylated
phenanthridine VII.
DOI: 10.1039/D0OB00136H
References
1
a) I. W. Achkar, F. Mraiche, R. M. Mohammad, S. Uddin, Future
Med. Chem, 2017, 9, 933-950. b) T. Nakanishi, M. Suzuki, A.
Saimoto, T. Kabasawa, J. Nat. Prod., 1999, 62, 864-867. c) A.-
H. O. Bashir, M. Toshio, A. Shin, M. Hisashi, Y. Masayuki, J. Nat.
Prod. 2004, 67, 1119-1124.
2
3
a) J. Bouquet, M. Rivaud, S. Chevalley, E. Deharo, V. Jullian, A.
Valentin, Malaria Journal, 2012, 11, 1-8. b) K. Morohashi, A.
Yoshino, A.Yoshimori, S. Saito, S. Tanuma, K. Sakaguchi, F.
Sugawara, Biochem. Pharmacol., 2005, 70, 37-46.
T. Nakanishi, A. Masuda, M. Suwa, Y. Akiyama, N. Hoshino-
Abe, M. Suzuki, Bioorg. Med. Chem. Lett., 2000, 10, 2321-
2323.
T. Ishikawa, Med. Res. Rev., 2001, 21, 61-72.
F. Menga, G. Zuo, X. Hao, G. Wang, H. Xiao, J. Zhang, G.J. Xua,
Ethnopharmacol, 2009, 125, 494-496.
4
5
6
7
A. Parhi, C. Kelley, M. Kaul, D.S. Pilch, E.J. LaVoie, Bioorg. Med.
Chem. Lett., 2012, 22, 7080-7083.
For selected examples see: a) L. Sripada, J.A. Teske, A. Deiters,
Org. Biomol. Chem., 2008, 6, 263-265. b) R. Yanada, K.
Hashimoto, R. Tokizane, Y. Miwa, H. Minami, K. Yanada, J. Org.
Chem., 2008, 73, 5135-5138.
8
9
For selected examples see: a) G. Maestri, E. Lacôte, C. Ollivier,
M.-H. Larraufie, É. Derat, M. Malacria, L. Fensterbank, Org.
Lett., 2010, 12, 5692-5695. b) T. Gerfaud, L. Neuville, J. Zhu,
Angew. Chem. Int. Ed., 2009, 48, 572-577. c) J. Peng, T. Chen,
C. Chen, B. Li, J. Org. Chem., 2011, 76, 9507. d) X. Bao, W. Yao,
Q. Zhu, Y. Xu, Eur. J. Org. Chem., 2014, 33, 7443-7450.
For selected examples see: a) B. Zhang, C. Mück-Lichtenfeld,
C.G. Daniliuc, A. Studer, Angew. Chem. Int. Ed., 2013, 52,
10792-10795. b) Y. Cheng, H. Jiang, Y. Zhang, S. Yu, Org. Lett.,
2013, 15, 5520. c) Q. Wang, X. Dong, T. Xiao, L. Zhou, Org.
Lett., 2013, 15, 4846-4849. d) T.H. Zhu, S. Y. Wang, Y. Q. Tao,
T. Q. Wei, S. Ji, Org. Lett., 2014, 16, 1260-1263. e) J. Huang, Y.
He, Q. Zhu, Z. Xia, J. Lei, J. Zhao, Org. Lett., 2014, 16, 2546-
2549. f) T. Xiao, L. Li, G. Lin, Q. Wang, P. Zhang, Z.W. Mao,
Green Chem., 2014, 16, 2418-2421. g) J. Liu, C. Fan, H. Yin, C.
Qin, G. Zhang, X. Zhang, H. Yi, A. Lei, Chem. Commun., 2014,
50, 2145-2147. h) S. Lu, Y. Gong, D. Zhou, J. Org. Chem., 2015,
80, 9336-9341. i) X. Zhou, P. Wang, L. Zhang, P. Chen, M. Ma,
N. Song, S. Ren, M. Li, J. Org. Chem., 2018, 83, 588-603. j) L.
Wang, W. Xiong, Y. Peng, Q. Ding, Org. Biomol. Chem., 2018,
16,8837-8844.
Scheme 4. Proposed mechanism.
Conclusions
In summary, a new protocol for the synthesis of 6-alkylated
phenanthridines using xanthates as radical precursors under
visible-light photoredox catalysis is described. We have
demonstrated that the use of xanthate-based radical chemistry
broadly expands the scope and streamlines the synthesis of 6-
alkylated phenanthridine derivatives through the photoredox
neutral somophilic isocyanide insertion. Electrophilic radicals
derived from nitriles, aromatic and aliphatic ketones,
malonates, and amide derivatives, as well as radicals derived
from phthalimidomethyl and benzylic derivatives, were
successfully introduced. The reaction proceeds under mild
conditions without a stoichiometric amount of oxidant. Thirty
novel phenanthridine scaffolds were synthesized with yields
ranging from 24 to 76%.
10 M. Tobisu, K. Koh, T. Furukawa, N. Chatani, Angew. Chem., Int.
Ed., 2012, 51, 11363-11366.
11 For selected examples see: a) D. Leifert, C.G. Daniliuc, A.
Studer, Org. Lett., 2013, 15, 6286-6289. b) B. Zhang, C.G.
Daniliuc, A. Studer Org. Lett., 2014, 16, 250-253. c) L. Wang,
W. Sha, W Q. Dai, X. Feng, W. Wu, H. Peng, B. Chen, J. Cheng,
Org. Lett., 2014, 16, 2088-2091. d) Z.Q. Zhu, T.T. Wang, P. Bai,
Z.Z. Huang, Org. Biomol. Chem., 2014, 12, 5839-5842. e) J. J.
Cao, T. H. Zhu, S. Y. Wang, Z. Y. Gu, X. Wang, S. J. Ji, Chem.
Commun., 2014, 50, 6439-6442. f) W. Sha, J. T. Yu, Y. Jiang, H.
Yang, J. Cheng, Chem. Commun., 2014, 50, 9179-9181. g) Y.
Xu, Y. Chen, W. Li, Q. Xie, L. Shao, J. Org. Chem., 2016, 81,
8426-8435. h) W. S. Guo, Q. Dou, J. Hou, L. R. Wen, M. Li, J.
Org. Chem., 2017, 82, 7015-7022. i) W.-Q. Shi, S. Liu, C.-Z.
Wang, Y. Huang, F.-L. Qing and X.-H. Xu, J. Org. Chem., 2018,
83, 15236-15244.
12 For some reviews see: a) J. M. R. Narayanam, C. R. J.
Stephenson, Chem. Soc. Rev., 2011, 40, 102-113. b) J. W.
Tucker, c. R. J. Stephenson, J. Org. Chem., 2012, 77, 1617-
1622. c) T. P. Nicholls, D. Leonori, A. C. Bissember, Nat. Prod.
Rep., 2016, 33, 1248-1254. d) M.H. Shaw, J. Twilton, D. W. C.
MacMillan, J. Org. Chem., 2016, 81, 6898-6926. e) L. Marzo, S.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
Financial support from PAPIIT-DGAPA (project IN208719) is
gratefully acknowledged. P. L.-M. thanks CONACYT for Ph.D.
scholarship (No. 308233). We also thank R. Patiño, A. Peña, E.
Huerta, I. Chavez, H. Ríos, R. Gaviño, B. Quiroz, Ma. C. García-
González, L. Velasco, J. Pérez and A. Jiménez-Sánchez for
technical support.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins