bond at the ortho-position, and the subsequent oxidative
addition of the Pd to the aryl bromide easily took place. This
coordination effect cannot be expected in the case of the other
heteroaryl bromides listed in Table 2. Interestingly, the use of
i-PrOH instead of 50% i-PrOH as the solvent for the coupling
reactions led to excellent results and the desired products
were obtained in nearly quantitative yields (Table 2, entries 8, 10
and 12).
Notes and references
1 For reviews of the palladium-catalyzed Suzuki–Miyaura coupling
reactions see: N. Miyaura, Top. Curr. Chem., 2002, 219, 11–59;
A. Suzuki, J. Organomet. Chem., 1999, 576, 147–168; N. Miyaura and
A. Suzuki, Chem. Rev., 1995, 95, 2457–2483.
2 K. Billingsley and S. L. Buchwald, J. Am. Chem. Soc., 2007, 129,
3358–3366; T. E. Barder, S. D. Walker, J. R. Martinelli and
S. L. Buchwald, J. Am. Chem. Soc., 2005, 127, 4685–4696;
T. E. Barder and S. L. Buchwald, Org. Lett., 2004, 6, 2649–2652.
3 N. Kudo, M. Perseghini and G. C. Fu, Angew. Chem., Int. Ed., 2006, 45,
1282–1284.
The Suzuki–Miyaura coupling reaction encompassed the
coupling between the heteroaryl boronic acids and heteroaryl
bromides. 3-Bromoquinoline, 5-bromopyrimidine, 2-bromo-5-
methylthiophene and 5-bromoindole possessing the non-
protected NH group on the indole ring smoothly reacted with
heteroaryl boronic acids under Pd/C–Na3PO4–i-PrOH–80 uC
conditions (Table 3). It is noteworthy that the present protocol
is applicable to sulfur containing heterocycles as substrates
(Table 3, entries 3 and 5 and also Table 1, entry 3), a reaction
which has previously been plagued by several limitations involving
protodeboronation2a,10 and catalyst poisoning of the sulfur
atom.11
4 G. A. Molander and B. Biolatto, J. Org. Chem., 2003, 68, 4302–4314.
5 I. Kondolff, H. Doucet and M. Santelli, Synlett, 2005, 2057–2061.
6 C.-L. Deng, S.-M. Guo, Y.-X. Xie and J.-H. Li, Eur. J. Org. Chem.,
2007, 1457–1462.
7 F.-X. Felpin, T. Ayad and S. Mitra, Eur. J. Org. Chem., 2006,
2679–2690; G. Cravotto, M. Beggiato, A. Penoni, G. Palmisano,
S. Tollari, J.-M. Le´veˆque and W. Bonrath, Tetrahedron Lett., 2005, 46,
2267–2271; T. Tagata and M. Nishida, J. Org. Chem., 2003, 68,
9412–9415; A. Arcadi, G. Cerichelli, M. Chiarini, M. Correa and
D. Zorzan, Eur. J. Org. Chem., 2003, 4080–4086; M. G. Organ and
S. Mayer, J. Comb. Chem., 2003, 5, 118–124; D. A. Conlon, B. Pipik,
S. Ferdinand, C. R. LeBlond, J. R. Sowa, Jr., B. Izzo, P. Collins,
G.-J. Ho, J. M. Williams, Y.-J. Shi and Y. Sun, Adv. Synth. Catal.,
2003, 345, 931–935.
8 Roschangar et al. described the coupling between 2-iodothiophene and
5-(diethoxymethyl)-2-furanboronic acid as the particular case. See:
M. S. McClure, F. Roschangar, S. J. Hodson, A. Millar and
M. H. Osterhout, Synthesis, 2007, 1681–1685.
9 T. Maegawa, Y. Kitamura, S. Sako, T. Udzu, A. Sakurai, A. Tanaka,
Y. Kobayashi, K. Endo, U. Bora, T. Kurita, A. Kozaki, Y. Monguchi
and H. Sajiki, Chem.–Eur. J., 2007, 13, 5937–5943.
10 N. Miyaura, in Metal-Catalyzed Cross-Coupling Reactions, ed. A. de
Meijere and F. Diederich, Wiley-VCH, Weinheim, 2nd edn, 2004, vol. 1,
ch. 2, pp. 80–82.
11 A. S. Guram, A. O. King, J. G. Allen, X. Wang, L. B. Schenkel, J. Chan,
E. E. Bunel, M. M. Faul, R. D. Larsen, M. J. Martinelli and P. J. Reider,
Org. Lett., 2006, 8, 1787–1789; N. T. S. Phan, J. Khan and P. Styring,
Tetrahedron, 2005, 61, 12065–12073.
We have developed a mild and efficient protocol for the ligand-
free and heterogeneous Pd/C-catalyzed hetero Suzuki–
Miyaura coupling reaction. To the best of our knowledge,
this methodology is the first to be reported which has
widespread application for the synthesis of various heterobiaryl
compounds using a heterogeneous catalyst under ligand-free
conditions. We anticipate that this approach will offer an
alternative synthetic strategy for the practical construction of
heterobiaryl compounds.
We thank the N. E. Chemcat Corporation for the gift of the
10% Pd/C.
This journal is ß The Royal Society of Chemistry 2007
Chem. Commun., 2007, 5069–5071 | 5071