internal oxidant in the reaction. It is important to mention
that this attractive strategy for using the directing group itself
as an oxidant mostly involves NꢀO bond (N-oxide, oxime,
N-methoxyamide) cleavage for the redox process.16 Our
continuous interest in CꢀH bond functionalization17 and
isoquinoline synthesis18 prompted us to explore the possibi-
lity of using other functionality (other than NꢀO bond) as an
internal oxidant in the CꢀH activation reaction. Herein we
report an efficient method for the synthesis of isoquinolines
from arylhydrazones catalyzed by [RhCp*Cl2]2. It is note-
worthy that the hydrazone moiety has rarely been as a
directing group for CꢀH bond activation reaction.19
The reaction of acetophenone N,N-dimethylhydrazone
1a withdiphenylacetylene (2a) in the presence of 2.5 mol %
of [RhCp*Cl2]2 and 1 equiv of AcOH in MeOH at 90 °C
for 8 h gave 1-methyl-3,4-diphenylisoquinoline 3aa in 93%
isolated yield. The structure of compound 3aa was thor-
oughly characterized by its 1H and 13C NMR and HRMS
data. The choice of solvent and additives is very crucial for
the success of the present Rh(III)-catalyzed CꢀH bond
activation and annulation reaction. We tested various
solvents such as toluene, 1,4-dioxane, 1,2-dichloroethane,
THF, EtOAc, acetone, and MeCN for the reaction of 1a
with 2a to form 3aa, and in all cases, low or no product
yields were observed (see the Supporting Information for
the detailed optimization study). In the absence of acetic
acid, the reaction gave only a trace of the product. The use
of dichloroacetic acid or acetate salts like AgOAc, NaOAc,
KOAc, and CsOAc gave product 3aa in 17ꢀ30% yields.
Having the optimized reaction conditions in hand, we
explored the scope of the present reaction, and the results
are shown in Table 1. Thus, the reaction of various
acetophenone hydrazones 1bꢀi having both electron-
donating and -withdrawing groups with 2a gave the corre-
sponding substituted isoquinolines 3baꢀia in good to
excellent yields (Table 1, entries 2ꢀ9). Under the same
Figure 1. Isoquinoline cored natural and useful compounds.
become important for the construction of carbonꢀcarbon
and carbonꢀheteroatom bonds.10 In particular, Rh- and
Ru-catalyzed CꢀH bond activation reactions have displayed
a wide scope of applications in the synthesis of heterocyclic
and carbocyclic compounds11,12 such as isoquinoline
derivatives13ꢀ15 from aromatic imines or oximes with alkynes
using Rh(I) or Rh(III) as the catalysts. The synthesis of
isoquinolines from oxime derivatives does not require an
external oxidant;15 the NꢀO bond of oxime acts as an
(8) (a) Korivi, R. P.; Cheng, C.-H. Org. Lett. 2005, 7, 5179. (b)
Korivi, R. P.; Wu, Y. C.; Cheng, C. H. Chem.;Eur. J. 2009, 15, 10727.
(c) Shih, W.-C.; Teng, C. C.; Parthasarathy, K.; Cheng, C.-H. Chem.;
Asian J. 2012, 7, 306.
(9) (a) Roesch, K. R.; Larock, R. C. J. Org. Chem. 1998, 63, 5306. (b)
Roesch, K. R.; Larock, R. C. Org. Lett. 1999, 1, 553. (c) Dai, G. X.;
Larock, R. C. Org. Lett. 2001, 3, 4035.
(16) (a) Wu, J.; Cui, X.; Chen, L.; Jiang, G.; Wu, Y. J. Am. Chem.
Soc. 2009, 131, 13888. (b) Tan, Y.; Hartwig, J. F. J. Am. Chem. Soc.
2010, 132, 3676. (c) Ng, K.-H.; Chan, A. S. C.; Yu, W.-Y. J. Am. Chem.
Soc. 2010, 132, 12862. (d) Guimond, N.; Gouliaras, C.; Fagnou, K.
J. Am. Chem. Soc. 2010, 132, 6908. (e) Willwacher, J.; Rakshit, S.; Glorius,
F. Org. Biomol. Chem. 2011, 9, 4736. (f) Li, B.; Feng, H.; Xu, S.; Wang,
B. Chem.;Eur. J. 2011, 17, 12573. (g) Li, B.; Ma, J.; Wang, N.; Feng, H.;
Xu, S.; Wang, B. Org. Lett. 2012, 14, 736. (h) Wang, H.; Glorius, F.
Angew. Chem., Int. Ed. 2012, 51, 7318. (i) Zheng, L.; Ju, J.; Bin, Y.; Hua,
R. J. Org. Chem. 2012, 77, 5794. (j) Xu, L.; Zhu, Q.; Huang, G.; Cheng,
B.; Xia, Y. J. Org. Chem. 2012, 77, 3017. (k) Shen, Y.; Liu, G.; Zhou, Z.;
Lu, X. Org. Lett. 2013, 15, 3366.
(17) (a) Gandeepan, P.; Parthasarathy, K.; Cheng, C.-H. J. Am.
Chem. Soc. 2010, 132, 8569. (b) Gandeepan, P.; Hung, C.-H.; Cheng,
C.-H. Chem. Commun. 2012, 48, 9379. (c) Gandeepan, P.; Cheng, C.-H.
J. Am. Chem. Soc. 2012, 134, 5738. (d) Gandeepan, P.; Cheng, C.-H.
Org. Lett. 2013, 15, 2084.
(18) (a) Jayakumar, J.; Parthasarathy, K.; Cheng, C.-H. Angew.
Chem., Int. Ed. 2012, 51, 197. (b) Karthikeyan, J.; Haridharan, R.;
Cheng, C.-H. Angew. Chem., Int. Ed. 2012, 49, 12343. (c) Parthasarathy,
K.; Senthilkumar, N.; Jayakumar, J.; Cheng, C. ꢀH. Org. Lett. 2012, 14,
3478. (d) Muralirajan, K.; Cheng, C.-H. Chem.;Eur. J. 2013, 19, 6198.
(e) Senthilkumar, N.; Parthasarathy, K.; Gandeepan, P.; Cheng, C.-H.
Chem.;Asian J. 2013, 8, 2175. (f) Luo, C.-Z.; Gandeepan, P.; Jayakumar,
J.; Parthasarathy, K.; Chang, Y. -W.; Cheng, C.-H. Chem.;Eur. J. 2013, 19,
14181. (g) Luo, C.-Z.; Gandeepan, P.; Cheng, C.-H. Chem. Commun. 2013,
49, 8528. (h) Huang, P.-C.; Gandeepan, P.; Cheng, C.-H. Chem. Commun.
2013, 49, 8540.
(10) For reviews, see: (a) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu,
J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094. (b) Lyons, T. W.; Sanford,
M. S. Chem. Rev. 2010, 110, 1147. (c) Ackermann, L. Chem. Rev. 2011,
111, 1315. (d) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215. (e)
Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45, 936. (f) Song,
G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651. (g) Shi, Z.; Zhang,
C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3381. (h) Cho, S. H.;
Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068.
(11) (a) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev.
2012, 112, 5879. (b) Kozhushkov, S. I.; Ackermann, L. Chem. Sci. 2013,
4, 886. (c) Ackermann, L. Acc. Chem. Res. 201310.1021/ar3002798.
(12) (a) Satoh, T.; Miura, M. Chem.;Eur. J. 2010, 16, 11212. (b)
Colby, D. A.; Tsai, A. S.; Bergman, R. G.; Ellman, J. A. Acc. Chem. Res.
2012, 45, 814. (c) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41,
3651. (d) Patureau, F. W.; Wencel-Delord, J.; Glorius, F. Aldrichimica
Acta 2012, 45, 31.
(13) (a) Lim, S.-G.; Lee, J. H.; Moon, C. W.; Hong, J.-B.; Jun, C.-H.
Org. Lett. 2003, 5, 2759. (b) Parthasarathy, K.; Cheng, C.-H. J. Org.
Chem. 2009, 74, 9359.
(14) (a) Guimond, N.; Fagnou, K. J. Am. Chem. Soc. 2009, 131,
12050. (b) Fukutani, T.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M.
Chem. Commun. 2009, 5141.
(15) (a) Too, P. C.; Wang, Y.-F.; Chiba, S. Org. Lett. 2010, 12, 5688.
(b) Too, P. C.; Chua, S. H.; Wong, S. H.; Chiba, S. J. Org. Chem. 2011,
76, 6159. (c) Guimond, N.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem.
Soc. 2011, 133, 6449. (d) Hyster, T. K.; Rovis, T. Chem. Commun. 2011,
47, 11846. (e) Zhang, S.; Chen, D.; Zhao, M.; Zhao, J.; Jia, A.; Li, X.
Adv. Synth. Catal. 2011, 353, 719.
(19) Chen, S.; Yu, J.; Jiang, Y.; Chen, F.; Cheng, J. Org. Lett. 2013,
15, 4754.
Org. Lett., Vol. 15, No. 22, 2013
5751