P.-P. Zhang et al. / Tetrahedron Letters 50 (2009) 4455–4458
4457
Table 3
Catalyst recycle study
obtained for fresh catalyst, demonstrating the robustness of the
Pd–CNT system (Table 3).
Ph
Br
Our catalyst was characterized by transmission electron
microscopy, and the resulting TEM image clearly showed that
nano-sized Pd particles are supported on CNTs. Smaller and highly
dispersed palladium NPs are much more abundant than larger
aggregated ones (Fig. 1). We speculate that CNTs not only provided
a high surface-to-volume ratio backbone like other nano materials
did, but also possessed some unique stabilizing or accelerating fac-
tors for the active catalytic species. One of such factors could arise
from the residual carboxylic acid groups formed during oxidative
pre-treatment of CNTs in the preparation of the catalysts.16 Mech-
anistic investigations along this line have been initiated.
0.3 mol% Pd-CNT (reused)
PhB(OH)2, K2CO3
EtOH-H2O (2:1), reflux
3a
1a
O
O
Run
1
1st reuse
2nd reuse
3rd reuse
Reaction time (h)
Yield 3aa (%)
3
3
3
3.5
95
95
94
94
a
Isolated yields.
In summary, we have shown that multi-walled carbon nano-
tubes (MWCNTs) are excellent support for Pd0 and the resulting
Pd–CNT efficiently catalyzed Suzuki–Miyaura cross-coupling of
arylbromides with arylboronic acids. The reaction was carried
out in aqueous solvents or neat water without the assistance of
any ligands or additives, and the catalyst could be recovered by
simple filtration, thus meeting the criteria of green chemistry.
The low catalyst loading as well as simple reaction setup is also
economically attractive. More detailed catalyst characterizations
including EDX are underway. Extension of the use of Pd–CNT to
other Pd-catalyzed reactions is currently pursued.
Acknowledgments
Financial support from the National Natural Science Foundation
of China (20602008, 20832005), Shanghai Natural Science Founda-
tion (08ZR1400500), Shanghai Leading Academic Discipline Project
(B108), and Fudan University is gratefully acknowledged.
References and notes
1. For leading reviews, see: (a) Suzuki, A. In Boronic Acids; Hall, D. G., Ed.; Wiley-
VCH: Weinheim, 2005; (b) Miyaura, N. In Metal-Catalyzed Cross-Coupling
Reactions; de Meijere, A., Diederich, F., Eds., 2nd ed.; Wiley-VCH: Weinheim,
2004; (c)Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi,
E., Ed.; John Wiley & Sons: New York, 2002.
2. For coupling of aryl chlorides, see: (a) Littke, F. C.; Fu, G. C. Angew. Chem., Int. Ed.
2002, 41, 4176. and references cited therein; For coupling of aryl tosylates, see:
(b) Tang, Z.-Y.; Hu, Q.-S. J. Am. Chem. Soc. 2004, 126, 3058; (c) Nguyen, H. N.;
Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 11818.
Figure 1. TEM image of 5 wt % Pd-CNT catalyst.
3. For selected catalytic systems with high TONs, see (a) Feuerstein, M.; Doucet,
H.; Santelli, M. Tetrahedron Lett. 2001, 42, 6667; (b) Li, J.-H.; Liu, W.-J. Org. Lett.
2004, 6, 2809; (c) Albisson, D. A.; Bedford, R. B.; Lawrence, S. E.; Scully, P. N.
Chem. Commun. 1998, 2095.
4. Industrial scale coupling: (a) Urawa, Y.; Naka, H.; Miyazawa, M.; Souda, S.;
Ogura, K. J. Organomet. Chem. 2002, 653, 269; Solvent-free coupling: (b)
Kabalka, G. W.; Pagni, R. M.; Hair, C. M. Org. Lett. 1999, 1, 1423; (c) Nielsen, S. F.;
Peters, D.; Axelsson, O. Synth. Commun. 2000, 30, 3501.
5. a Selected novel phosphane ligands: Ref. 3a.; (b) Hu, Q.-S.; Lu, Y.; Tang, Z.-Y.;
Yu, H.-B. J. Am. Chem. Soc. 2003, 125, 2856; For leading reviews on Pd–N-
heterocyclic carbene catalysis, see: (c) Kantchev, E. A. B.; O’Brien, C. J.; Organ,
M. G. Angew. Chem., Int. Ed. 2007, 46, 2768; (d) Herrmann, W. A. Angew. Chem.,
Int. Ed. 2002, 41, 1290; For a review on Pd catalysts including palladacycles,
see: (e) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419; Selected water-
soluble ligands: (f) Casalnuovo, A. L.; Calabrese, J. C. J. Am. Chem. Soc. 1990, 112,
4324; (g) DeVasher, R. B.; Moore, L. R.; Shaughnessy, K. H. J. Org. Chem. 2004, 69,
7919.
6. a Amines as additive: Ref. 3b.; (b) Tao, B.; Boykin, D. W. Tetrahedron Lett. 2003,
44, 7993; (c) Tao, B.; Boykin, D. W. J. Org. Chem. 2004, 69, 4330; PEG as additive:
(d) Liu, L.; Zhang, Y.; Wang, Y. J. Org. Chem. 2005, 70, 6122; Quaternary
ammonium salts as PTC additive: (e) Badone, D.; Baroni, M.; Cardamone, R.;
Ielmini, A.; Guzzi, U. J. Org. Chem. 1997, 62, 7170; (f) Botella, L.; Najera, C.
Angew. Chem., Int. Ed. 2002, 41, 179.
With this encouraging result in hand, the scope of the Pd–CNT-
catalyzed Suzuki coupling was examined next (Table 2). Various
arylbromides were subject to the optimized conditions, and excel-
lent yields (up to quantitative) were obatined.13 Both electron-
deficient (entries 3 and 9) and electron-rich substrates (1e, 1k)
coupled efficiently. For some hydrophobic substrates (1b, 1d), the
difference of Na2CO3 and K2CO3 was significant, the use of the
latter markedly increased the reaction rate and yields owing to
possible template effect of the cation.14 Substrate with ortho-sub-
stitution to the reaction site (1c) gave lower yield due to higher
steric hindrance. Representative heteroaromatic substrates (1h,
1i) also underwent smooth coupling. It is noteworthy that Suzuki
coupling of hydrophilic substrates such as phenols (1k) and ben-
zoic acids (1j) can be carried out in neat water, which afforded
even better yields than the mixed solvents of aqueous ethanol (en-
tries 13–16). In addition, the unmasked carboxylic acid and phenol
group in these substrates, which often caused difficulties, were
both compatible with the present protocol.15 With regard to che-
moselectivity, this catalytic system did not affect arylchlorides
(1d), even that activated by a nitro group in the para-position at
a higher reaction temperature (entry 17).
7. For studies of limited scope using Pd/C, see: (a) Ennis, D. S.; McManus, J.;
Wood-Kaczmar, W.; Richardson, J.; Smith, G. E.; Carstairs, A. Org. Prep. Res. Dev.
1999, 3, 248; (b) Organ, M. G.; Mayer, S. J. Comb. Chem. 2003, 5, 118; (c)
LeBlond, C. R.; Andrews, A. T.; Sun, Y.; Sowa, J. R., Jr. Org. Lett. 2001, 3, 1555; (d)
Sakurai, H.; Tsukuda, T.; Hirao, T. J. Org. Chem. 2002, 67, 2721; For a review, see:
(e) Seki, M. Synthesis 2006, 2975; For an example of inorganic support (Pd/
zeolite), see: (f) Artok, L.; Bulut, H. Tetrahedron Lett. 2004, 45, 3881.
8. Pre-formed Pd nanoparticles as the catalyst: Li, Y.; Hong, X. M.; Collard, D. M.;
El-Sayed, M. A. Org. Lett. 2000, 2, 2385.
Catalyst recycling experiments were also carried out. Using the
recycled Pd–CNT, the subsequent runs went to completion in com-
parable reaction time, and the yields obtained were as good as that