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ChemComm
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COMMUNICATION
Journal Name
of high-value functionalized phenanthridines in very high yields.
Identification of acrylonitrile as a one-carbon synthon was a critical
Lam, J. Am. Chem. Soc., 2013, 135, 10829; (d) R. K. Chinnagolla, S. Pimparkar and
DOI: 10.1039/C9CC05717J
M. Jeganmohan, Org. Lett., 2012, 14, 3032; (e) S. Nakanowatari and L.
Ackermann, Chem. Eur. J., 2014, 20, 5409; For (3+2): (f) J. Zhang, A. Ugrinov and
P. Zhao, Angew. Chem. Int. Ed., 2013, 52, 6681; (g) Y. Q. Zhu and L. Dong, J. Org.
Chem., 2015, 80, 9973; (h) Y. Zhao, Z. He, S. Li, J. Tang, G. Gao, J. Lan and J. You,
Chem. Commun., 2016, 52, 4613; For (2+2+2+): (i) H. Chen, L. Ouyang, J. Liu, W.-
J. Shi, G. Chen and L. Zheng, J. Org. Chem., 2019, acs.joc.9b00926; For (4+1): (j) X.
Wu, B. Wang, S. Zhou, Y. Zhou and H. Liu, ACS Catal., 2017, 7, 2494.
a) H/D Exchange Experiment
N
NH2
standard conditions
(0%)
D
(0%)
D
CN
1a
+
D (0%)
2a
D2O (10 equiv)
3a 38%
,
1a 46%
,
b) Kinetic Isotope Effect Study
CN
4 For Ru-catalyzed [5+1] annulation: (a) P. Chen, J. Nan, Y. Hu, Q. Ma and Y. Ma,
Org. Lett., 2019, 21, 4812; (b) S. Reddy Chidipudi, M. D. Wieczysty, I. Khan and H.
W. Lam, Org. Lett., 2013, 15, 570; Other examples of transition-metal-catalyzed
[5+1] annulations: (c) D. J. Burns and H. W. Lam, Angew. Chem. Int. Ed., 2014, 53,
9931; (d) N. Casanova, A. Seoane, J. L. Mascareñas and M. Gulías, Angew. Chem.
Int. Ed., 2015, 54, 2374; (e) A. Cajaraville, J. Suárez, S. López, J. A. Varela and C.
Saá, Chem. Commun., 2015, 51, 15157; (f) R. Kuppusamy, K. Muralirajan and C.
H. Cheng, ACS Catal., 2016, 6, 3909.
standard conditions
NH2
N
pH/pD =2.45
kH/kD =2.80
NH2
N
+
2 to 10 h
D5
D4
1a
[D5]-1a
3a
[D4]-3a
c) Radical Quenching Experiment
standard conditions
radical scavenger (2 equiv)
CN
TEMPO (8 %), BHT (52 %)
1a
3a
2a
d) Plausible Mechanism for C-C Bond Cleavage
5 (a) S. De Sarkar, W. Liu, S. I. Kozhushkov and L. Ackermann, Adv. Synth. Catal.,
2014, 356, 1461; (b) M. P. Drapeau and L. J. Gooßen, Chem. Eur. J., 2016, 22,
18654; (c) C. Sambiagio, D. Schönbauer, R. Blieck, T. Dao-Huy, G. Pototschnig, P.
Schaaf, T. Wiesinger, M. F. Zia, J. Wencel-Delord, T. Besset, B. U. W. Maes and M.
Schnürch, Chem. Soc. Rev., 2018, 47, 6603.
6 Selected examples on free-amine directed C–H bond functionalization; with Ru-
catalysts: (a) C. Suzuki, K. Hirano, T. Satoh and M. Miura, Org. Lett., 2013, 15,
3990; (b) P. Villuendas and E. P. Urriolabeitia, J. Org. Chem., 2013, 78, 5254–
5263; (c) C. Suzuki, K. Morimoto, K. Hirano, T. Satoh and M. Miura, Adv. Synth.
Catal., 2014, 356, 1521; With Pd-catalysts: (d) Z. Zuo, J. Liu, J. Nan, L. Fan, W.
Sun, Y. Wang and X. Luan, Angew. Chem. Int. Ed., 2015, 54, 15385; (e) G. Jiang, S.
Wang, J. Zhang, J. Yu, Z. Zhang and F. Ji, Adv. Synth. Catal., 2019, 361, 1798; With
Rh-catalysts: (f) Q. Jiang, D. Duan-Mu, W. Zhong, H. Chen and H. Yan, Chem. Eur.
J., 2013, 19, 1903; (g) P. Bai, X. F. Huang, G. D. Xu and Z. Z. Huang, Org. Lett.,
2016, 18, 3058. For Ir-catalysts: (h) K. Yan, Y. Lin, Y. Kong, B. Li and B. Wang, Adv.
Synth. Catal., 2019, 361, 1570.
Ar
O
SbF6
Ar
H
O
Ar
Ar
Ar
[cat.]
N
[RuL]
N
NH
[cat.]
N
CH3CN
Ar
Ar
CN
[B]
cat. = [ArCO2Ru(p-cym)L]+SbF6- ; L = p-cymene
3
[A]
Scheme 3. Control experiments
parameter for achieving the concomitant C–C bond cleavage,
furnishing 6-unsubstituted phenanthridines in a succinct manner.
Also, the applications of this methodology in syntheses of bioactive
alkaloids like trisphaeridine and bicolorine add to the fruitfulness of
the protocol. Further applications of Ru(II)-catalyzed annulation are
currently ongoing in our laboratory.
7 (a) M. Suffnes and G. A. Cordell, The Alkaloids; Academic: New York, 1985; Vol. 25,
pp 178 (b) T. Ishikawa, Med. Res. Rev., 2001, 21, 61; (c) T. Nakanishi, M. Suzuki,
A. Saimoto and T. Kabasawa, J. Nat. Prod., 1999, 62, 864; (d) D. Castillo, M.
Sauvain, M. Rivaud and V. Jullian, Planta Med., 2014, 80, 902; (e) I. Zupkó, B.
Réthy, J. Hohmann, J. Molnár, I. Ocsovszki and G. Falkay, In Vivo (Brooklyn).,
2009, 23, 41; (f) G. Y. Park, J. J. Wilson, Y. Song and S. J. Lippard, Proc. Natl. Acad.
Sci., 2012, 109, 11987; (g) J. Bouquet, M. Rivaud, S. Chevalley, E. Deharo, V.
Jullian and A. Valentin, Malar. J., 2012, 11, 1; (h) Y. Ding, D. Qu, K. M. Zhang, X. X.
Cang, Z. N. Kou, W. Xiao and J. B. Zhu, J. Asian Nat. Prod. Res., 2017, 19, 53.
8 (a) L. M. Tumir, M. R. Stojković and I. Piantanida, Beilstein J. Org. Chem., 2014, 10,
2930; (b) V. Bisai, M. K. S. Shaheeda, A. Gupta and A. Bisai, Asian J. Org. Chem.,
We gratefully acknowledge SERB-DST for financial support. M.B.
also thanks IIT-Madras for the Institute Research Development
Award (IRDA). We also thank the Department of Chemistry, IIT-
Madras for instrumental facilities.
Conflicts of interest
There are no conflicts to declare.
2019, 8, 946.
9 (a) Y. Y. Liu, R. J. Song, C. Y. Wu, L. Bin Gong, M. Hu, Z. Q. Wang, Y. X. Xie and J. H.
Li, Adv. Synth. Catal., 2012, 354, 347; (b) Z. Liang, L. Ju, Y. Xie, L. Huang and Y.
Zhang, Chem. Eur. J., 2012, 18, 15816. (c) X. Bao, W. Yao, Q. Zhu and Y. Xu, Eur.
J. Org. Chem., 2014, 33, 7443. For a C–C bond cleavage of phthalimide, see: (d)
Y. C. Yuan, R. Kamaraj, C. Bruneau, T. Labasque, T. Roisnel and R. Gramage-
Doria, Org. Lett., 2017, 19, 6404.
10 At the current scenario, annulation did not take place with unactivated olefins
such as 1-octene and isopropenylbenzene.
11 W. Guo, S. Li, L. Tang, M. Li, L. Wen and C. Chen, Org. Lett., 2015, 17, 1232.
12 (a) W. L. Chen, C. Y. Chen, Y. F. Chen and J. C. Hsieh, Org. Lett., 2015, 17, 1613;
(b) G. Wang, W. Hu, Z. Hu, Y. Zhang, W. Yao, L. Li, Z. Fu and W. Huang, Green
Chem., 2018, 20, 3302.
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4 | J. Name., 2012, 00, 1-3
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