transformations have been extensively studied using Pd as
the catalyst and have become useful synthetic tools for the
construction of biaryl units.4,6,7 Recently, this synthetic
strategy for connecting aryl rings has been expanded to other
metals such as copper,8 rhodium,9 and ruthenium.10 These
successful developments prompted us to study the Rh-
catalyzed intermolecular11 oxidative cross-coupling of het-
eroarenes with chalcogenophenes.12 Several heterocyclic
derivatives such as oxazoles,7h,8cꢀe,12 thiazoles,7h,8d,12
imidazoles,8c,d,12 furans,7c,f,9c,9d,12 thiophenes,7i,9c,d,12 and
pyrroles7aꢀd,f,8e,12b have been studied to achieve CꢀH bond
functionalization. However such a transformation of seleno-
phenes and unsubstituted thiophene13 has not been accom-
plished to date. Herein we summarize our results on the
Rh-catalyzed oxidative cross-coupling of arenes and hetero-
arenes with chalcogenophenes.
Initially, the reaction of 2-(m-tolyl)pyridine (1a) with
2-methylthiophene (2a) was chosen as a model reaction to
optimize the reaction conditions.14 After screening several
parameters, it was revealed that the desired cross-coupling
product was formed in a high yield when 10 mol % of
[Cp*RhCl2]2 was employed as a catalyst in combination
with Cu(OAc)2 (2.8 equiv) and AgSbF6 (10 mol %) at
140 °C for 24 h. The desired cross-coupling products were
obtained in almost similar yields with 5 mol % of
[Cp*RhCl2]2 along withCu(OAc)2 (3.2 equiv) and AgSbF6
(20 mol %) as the oxidant at 140 °C for 48 h. Under the
optimized conditions, the reaction of 2-phenylpyridine and
N-phenylpyrazole derivatives with various thiophenes and
selenophene was examined to explore the scope of this
rhodium-catalyzed intermolecular oxidative cross-coupling.
As shown in Scheme 1, these reactions provided the
corresponding cross-coupling products in moderate to good
yields. The reaction of 2-(m-tolyl)pyridine (1a) with
2-methylthiophene (2a) afforded the corresponding coupling
(5) Catalytic CꢀC bond formation via nucleophilic ArꢀH bond
cleavage: (a) Fujiwara, Y.; Moritani, I.; Danno, S.; Asano, R.;
Teranishi, S. J. Am. Chem. Soc. 1969, 91, 7166. (b) Jia, C.; Kitamura,
T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633. Catalytic CꢀC bond
formation via directing group assisted ArꢀH bond cleavage: (c) Murai,
S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.;
Chatani, N. Nature 1993, 366, 529. (d) Kakiuchi, F.; Murai, S. Acc.
Chem. Res. 2002, 35, 826. (e) Murai, S. Proc. Jpn. Acad., Ser. B 2011, 87,
230. Stoichiometric cleavage of ArꢀH bond by metal ions: (f) van
Helden, R.; Verberg, G. Recl. Trav. Chim. Pays-Bas 1965, 84, 1263. (g)
Davidson, J. M.; Triggs, C. Chem. Ind. 1966, 457. (h) Davidson, J. M.;
Triggs, C. J. Chem. Soc. (A) 1968, 1324. (i) Moritani, I.; Fujiwara, Y.
Tetrahedron Lett. 1967, 8, 1119.
(6) For recent reports of Pd-catalyzed oxidative cross-coupling reac-
tions, see: (a) Li, R.; Jiang, L.; Lu, W. Organometallics 2006, 25, 5973.
(b) Xia, J.-B.; You, S.-L. Organometallics 2007, 26, 4869. (c) Hull, K. L.;
Sanford, M. S. J. Am. Chem. Soc. 2007, 129, 11904. (d) Li, B.-J.; Tian,
S.-L.; Fang, Z.; Shi, Z.-J. Angew. Chem., Int. Ed. 2008, 47, 1115. (e)
Brasche, G.; Garcia-Fortanet, J.; Buchwald, S. L. Org. Lett. 2008, 10,
2207. (f) Wei, Y.; Su, W. J. Am. Chem. Soc. 2010, 132, 16377. (g) Zhao,
X.; Yeung, C. S.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 5837. (h)
Yeung, C. S.; Zhao, X.; Borduas, N.; Dong, V. M. Chem. Sci. 2010, 1,
331. (i) Lyons, T. W.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2011,
133, 4455. (j) Zhou, L.; Lu, W. Organometallics 2012, 31, 2124.
(7) For recent reports of Pd-catalyzed oxidative cross-coupling reac-
tions of heteroarenes, see: (a) Stuart, D. R.; Fagnou, K. Science 2007,
316, 1172. (b) Stuart, D. R.; Villemure, E.; Fagnou, K. J. Am. Chem. Soc.
2007, 129, 12072. (c) Dwight, T. A.; Rue, N. R.; Charyk, D.; Josselyn, R.;
DeBoef, B. Org. Lett. 2007, 9, 3137. (d) Potavathri, S.; Dumas, A. S.;
Dwight, T. A.; Naumiec, G. R.; Hammann, J. M.; DeBoef, B. Tetra-
hedron Lett. 2008, 49, 4050. (e) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am.
Chem. Soc. 2008, 130, 9254. (f) Potavathri, S.; Pereira, K. C.; Gorelsky,
S. I.; Pike, A.; LeBris, A. P.; DeBoef, B. J. Am. Chem. Soc. 2010, 132,
14676. (g) He, C.-Y.; Fan, S.; Zhang, X. J. Am. Chem. Soc. 2010, 132,
12850. (h) Li, Z.; Ma, L.; Xu, J.; Kong, L.; Wu, X.; Yao, H. Chem.
Commun. 2012, 48, 3763.
Scheme 1. Rhodium-Catalyzed Oxidative Cross-Coupling of
Pyridinyl and Pyrazole Directing Groupsa,b
(8) Copper-mediated oxidative cross-coupling reactions: (a) Jia,
Y.-X.; Kundig, E. P. Angew. Chem., Int. Ed. 2009, 48, 1636. (b) Bernini,
R.; Fabrizi, G.; Sferrazza, A.; Cacchi, S. Angew. Chem., Int. Ed. 2009, 48,
8078. (c) Kitahara, M.; Umeda, N.; Hirano, K.; Satoh, T.; Miura, M.
J. Am. Chem. Soc. 2011, 133, 2160. (d) Mao, Z.; Wang, Z.; Xu, Z.;
Huang, F.; Yu, Z.; Wang, R. Org. Lett. 2012, 14, 3854. (e) Nishino, M.;
Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed. 2012, 51, 6993.
(9) (a) Morimoto, K.; Itoh, M.; Hirano, K.; Satoh, T.; Shibata, Y.;
Tanaka, K.; Miura, M. Angew. Chem., Int. Ed. 2012, 51, 5359. (b)
Wencel-Delord, J.; Nimphius, C.; Patureau, F. W.; Glorius, F. Angew.
Chem., Int. Ed. 2012, 51, 2247. (c) Kuhl, N.; Hopkinson, M. N.; Glorius,
F. Angew. Chem., Int. Ed. 2012, 51, 8230. (d) Wencel-Delord, J.;
Nimphius, C.; Wang, H.; Glorius, F. Angew. Chem., Int. Ed. 2012, 51,
13001. Intramolecular oxidative coupling between aldehyde and arene
has been reported. (e) Wang, P.; Rao, H.; Hua, R.; Li, C.-J. Org. Lett.
2012, 14, 902.
(10) Guo, X.; Deng, G.; Li, C.-J. Adv. Synth. Catal. 2009, 351, 2071.
(11) Intermolecular arylꢀaryl, heteroarylꢀheteroaryl, and arylꢀ
heteroaryl cross-couplings catalyzed by Rh have been reported by
Glorius in refs 9b, 9c, and 9d, respectively. In ref 9c, several examples
of the reaction of thiophenes using Cu(OAc)2 as the oxidizing reagent
are presented.
(12) During preparation of our manuscript, two similar reports
appeared: (a) Dong, J.; Long, Z.; Song, F.; Wu, N.; Guo, Q.; Lan, J.;
You, J. Angew. Chem., Int. Ed. 2013, 52, 580. (b) Qin, X.; Liu, H.; Qin,
D.; Wu, Q.; You, J.; Zhao, D.; Guo, Q.; Huang, X.; Lan, J. Chem. Sci.
201310.1039/C3SC22241A.
a Reaction conditions: 1aꢀi (0.25 mmol), 2aꢀf (0.75 mmol),
[Cp*RhCl2]2 (10 mol %), Cu(OAc)2 (2.8 equiv), AgSbF6 (10 mol %),
Yields of isolated products.
b
and DMA (1.0 mL), 24 h, 140 °C.
c
[Cp*RhCl2]2 (5 mol %), AgSbF6 (20 mol %), Cu(OAc)2 (3.2 equiv),
DMA (1.0 mL), 48 h, 140 °C. d 5ꢀ10% of 30 was observed by 1H NMR.
e Isolated as mixture (ratio was determined by 1HNMR). f Without AgSbF6.
product 3a in 75% yield. In this reaction, starting material
1a was completely consumed. Simple 2-phenylpyridine (1b)
reacted with 2-methylthiophene (2a) to afford the corre-
sponding coupling product 3d in 60% yield. Electron-rich
(13) This is partly because thiophene tends to undergo oligomeriza-
tion. See for instance ref 9c.
(14) See Supporting Information.
B
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