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Notes and references
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Scheme 1 Formation of Ru(II)-catalyzed isoquinolinium salt.
3 For stoichiometric metal mediated reaction, see: (a) G. Wu,
A. L. Rheingold, S. J. Geib and R. F. Heck, Organometallics, 1987,
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Chem., 1988, 53, 3228.
4 For metal catalyzed reaction of ortho-halo imines, see:
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5 For reviews, see: (a) X. Chen, K. M. Engle, D.-H. Wang and J.-Q. Yu, Angew.
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8 (a) G. Zhang, L. Yang, Y. Wang, Y. J. Xie and H. Huang, J. Am. Chem.
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with 4a afforded the respective isoquinolinium salts in excellent
yields. Similarly, oct-4-yne 2b and 1,2-di(thiophen-2-yl)ethyne 2g
nicely reacted with 4a to afford products 5ab and 5ag in 87 and
91% yields respectively. Unsymmetrical alkynes 2h–k reacted effi-
ciently with 4a to give respective isoquinolinium products 5ah–ak in
excellent yields and regioselectivity. Benzophenone imines 4c–e with
N-n-butyl, -benzyl and -3,4-substituent reacted with 2a to give
corresponding isoquinolinium salts 5ca–5ea in 89, 92 and 82%
yields, respectively. Similarly, the reaction of fluorenone imine 4f
with 2a gave the desired isoquinolinium salt 5fa in 89% yield. To
understand the regio-selectivity of benzophenone imine with
different substituents on the phenyl rings in this catalytic reac-
tion, we chose imine derived from 4-bromobenzophenone 4b as
1
the substrate for the reaction with 2a. The H NMR spectrum of
the product mixture showed that C–H activation occurred equally
in both substituted and unsubstituted phenyl rings to give a
mixture of 5ba and 5ba0 in a 1 : 1 ratio in 83% combined yield
(Table 2).
In addition to the use of [RhCp*Cl2]2 as the catalyst, we also
tested the catalytic activity of ruthenium complexes. Gratifyingly,
the reaction of benzophenone imine 4a with 2a in the presence
of 2 mol% of [Ru(p-cymene)Cl2]2, AgBF4 (1 equiv.) and Cu(OAc)2
(1 equiv.) in t-amylOH at 110 1C for 4 h gave 5aa in 81% isolated
yield (Scheme 1). The result indicates that ruthenium complexes
can also be employed in the present catalytic reaction.11
Based on our experimental results and the known metal-
catalyzed directing group-assisted C–H bond activation reactions,6,7
a plausible mechanism for the present rhodium(III)-catalyzed reac-
tion likely involves the removal of chloride by Ag+ in [RhCp*Cl2]2 to
generate a more catalytically active rhodium di-cation.8a Then the
coordination of the imine substrate to the rhodium(III) center,
followed by ortho C–H bond activation form a 5-membered
rhodacycle. Alkyne coordination and subsequent insertion
provides a 7-membered rhodacycle. Finally, reductive elimina-
tion gives the isoquinolinium salt product.
9 (a) Y. Nishiyama, M. Moriyasu, I. Ichimaru, K. Iwasa, A. Kato, S. G.
Mathenge, P. B. Chalo Mutiso and F. D. Juma, Phytochemistry, 2004,
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K. Song, J. Biol. Chem., 2010, 285, 2986; (g) A. Ponte-Sucre, T. Gulder,
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52, 626.
In conclusion, we have successfully developed a new method
for the synthesis of various 1-substituted isoquinolinium salts
from ketimines and alkynes via rhodium(III)-catalyzed C–H
bond activation. Various substituted acetophenone and benzo-
phenone imines derived from different aliphatic and aromatic
amines were successfully employed in this C–H bond activation
and annulation reaction. Further applications of this metho-
dology to natural products synthesis are currently under study
in our laboratory.
10 (a) P. Gandeepan, K. Parthasarathy and C.-H. Cheng, J. Am. Chem. Soc.,
2010, 132, 8569; (b) K. Muralirajan, K. Parthasarathy and C.-H. Cheng,
Org. Lett., 2012, 14, 4262; (c) P. Gandeepan, C.-H. Hung and C.-H. Cheng,
Chem. Commun., 2012, 14, 3478; (d) P. Gandeepan and C.-H. Cheng,
J. Am. Chem. Soc., 2012, 134, 5738; (e) J. Karthikeyan, R. Haridharan and
C.-H. Cheng, Angew. Chem., Int. Ed., 2012, 49, 12343; ( f ) P. Gandeepan
and C.-H. Cheng, Org. Lett., 2013, 15, 2084; (g) N. Senthilkumar,
K. Parthasarathy, P. Gandeepan and C.-H. Cheng, Chem.–Asian J.,
2013, 8, 2175; (h) P. C. Huang, P. Gandeepan and C.-H. Cheng, Chem.
Commun., 2013, 49, 8540; (i) S.-C. Chuang, P. Gandeepan and
C.-H. Cheng, Org. Lett., 2013, 15, 5750.
We thank the National Science Council of Republic of China
(NSC-102-2628-M-007-005) for support of this research.
11 J. Li and L. Ackermann, Tetrahedron, 2013, DOI: 10.1016/j.tet.2013.10.003.
3108 | Chem. Commun., 2014, 50, 3106--3108
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