A. d. C. Silva et al. / Tetrahedron Letters 51 (2010) 3883–3885
3885
48, 8153–8156; (e) Barros, J. C.; Souza, A. L. F.; Lima, P. G.; Silva, J. F. M.;
Antunes, O. A. C. Appl. Organomet. Chem. 2008, 22, 249–252.
2. (a) Li, C. Chem. Rev. 2005, 105, 3095–3166; (b) Suzuki, A. Acc. Chem. Res. 1982,
15, 178–184.
To generalize our methodology, other substrates were used. The
results are shown in Table 3.
Entry 1 (Table 3) presents the highest TON (9700) since it cor-
responds to the most activated aryl halide among those tested;
for less activated aryl iodides, reaction time (Table 3, entries 2
and 3) or Pd load (Table 3, entries 4 and 5) enhancements were
needed to improve yields of the corresponding reactions. Aryl bro-
mide (Table 3, entry 6) and chloride (Table 3, entry 7) needed 24 h
to react and gave yields of 74% and 17%, respectively, correspond-
ing to the order of reactivity of aryl halides. Even when a greater Pd
amount was supplied using chlorobenzene as substrate (Table 3,
entry 8), a yield of only 31% was obtained, which led to a dramatic
decrease of TON value. Entry 9 (Table 3) evidences low conversion,
so the GC–MS yield was used, and the corresponding product was
not isolated. On the other hand, as in entries 1 and 2 (Table 3), en-
try 10 shows an excellent result. Heteroarylboronic acids were also
tested, showing low reactivity toward aryl halides, whichever be
the substituent, electron-withdrawing and electron-donating (en-
tries 11 and 12). These results are not appealing as those observed
when couplings with phenyl boronic acid were accomplished (Ta-
ble 3, entries 1 and 3). Such results allowed us to infer that the
transmetallation is a slow step of the Suzuki–Miyaura catalytic cy-
cle. For entries 13 and 14, the occurrence of reaction is not ob-
served. By contrast, entry 15 shows that 5-bromopyrimidine is as
reactive as 4-iodonitrobezene (Table 3, entry 1), resulting in 98%
of isolated yield. All the compounds were characterized and ana-
lyzed by GC–MS, 1H NMR and 13C NMR.13
3. (a) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 15, 2419–2440; (b) Smith, G.
B.; Dezeny, G. C.; Hughes, D. L.; King, A. O.; Verhoeven, T. R. J. Org. Chem. 1994,
59, 8151–8156; (c) Ennis, D. S.; McManus, J.; Wood-Kaczmar, W.; Richardson,
J.; Smith, G. E.; Carstairs, A. Org. Proc. Res. Dev. 1999, 3, 248–252; (d) Miyaura,
N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
4. Castanet, A. S.; Colobert, F.; Desmurs, J. R.; Schlama, T. J. Mol. Catal. A: Chem.
2002, 182, 481–487.
5. (a) Razler, T. M.; Hsiao, Y.; Qian, F.; Fu, R.; Khan, R. K.; Doubleday, W. J. Org.
Chem. 2009, 74, 1381–1384; (b) Han, W.; Liu, C.; Jin, Z. Adv. Synth. Catal. 2008,
350, 501–508; (c) Han, W.; Liu, C.; Jin, Z.-L. Org. Lett. 2007, 9, 4005–4007; (d)
Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68, 888–892.
6. Silva, A. C.; Souza, A. L. F.; Antunes, O. A. C. J. Organomet. Chem. 2007, 692,
3104–3107.
7. Souza, A. L. F.; Silva, L. C.; Oliveira, B. L.; Antunes, O. A. C. Tetrahedron Lett. 2008,
49, 3895–3898.
8. Souza, A. L. F.; Silva, A. C.; Antunes, O. A. C. Appl. Organomet. Chem. 2009, 23, 5–
8.
9. General procedure for Suzuki reaction: In a 25 mL flask containing aryl halide
(1 mmol), boronic acid (1.1 mmol), K2CO3 (3 mmol), and Pd2(dba)3 (0.01 mol %)
in PEG 300 (4 g). The reaction was then kept under stirring at 55 °C for 1 hour.
After the reaction was complete, the reaction mixture was extracted with
diethyl ether, then the organic phase was filtered under Celite, washed with
water and dried over anhydrous sodium sulfate, and the solvent was
eliminated by vacuum. The crude product was analyzed by GC–MS, 1H NMR,
and 13C NMR.
10. Sonication was performed in a thermostatic Branson 1210 ultrasonic cleaner
with a frequency of 47 kHz and a power of 250 W.
11. (a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168; (b) Stanforth, S. P.
Tetrahedron 1998, 54, 263–303; (c) Kotha, S.; Lahiri, K.; Kashinath, D.
Tetrahedron 2002, 9633–9695.
12. After each run, the product was extracted with diethyl ether as in Ref. 9. Then,
the catalyst solution was reused after a solvent elimination by vacuum.
13. Biphenyl: White solid. 1H NMR (CDCl3, 200 MHz) d 7.81–7.65 (4H, d), 7.55–7.42
(4H, dd), 7.37–7.27 (2H, d); 13C NMR (CDCl3, 50 MHz) d 141.47, 128.95, 127.45,
127.37; GC–MS: m/z = 77, 154. 4-Methoxybiphenyl: White solid. 1H NMR
(200 MHz, CDCl3) d 7.48–7.42 (4H, m), 7.36 (2H, t), 7.32 (1H, d), 6.91 (2H, d),
3.75 (3H, s); 13C NMR (50 MHz, CDCl3) d 159.36, 141.03, 133.98, 128.91,
128.34, 126.85, 114.41, 55.52; GC–MS: m/z = 115, 141, 169, 184. 4-
Nitrobiphenyl: Yellow solid. 1H NMR (CDCl3, 200 MHz) d 8.30 (2H, d), 7.74
(2H, d), 7.64 (2H, d), 7.52–7.44 (3H, m); 13C NMR (CDCl3, 50 MHz) d 146.6,
146.09, 137.74, 128.13, 127.89, 126.76, 126.35, 123.06; GC–MS: m/z = 141,
152, 199. 4-Phenylacetophenone: Pale yellow solid. 1H NMR (200 MHz, CDCl3) d
8.06–8.02 (2H, d), 7.72–7.62 (4H, m), 7.52–7.27 (3H, m), 2.65 (3H, s); 13C NMR
(50 MHz, CDCl3) d 197.86, 145.96, 140.06, 136.09, 129.13, 129.08, 128.40,
127.44, 127.39, 26.78; GC–MS: m/z = 76, 152, 181, 196. 1-(40-Fluoro-biphenyl-4-
yl)-ethanone: White solid. 1H NMR (CDCl3, 200 MHz) d 7.95–7.91 (2H, d), 7.56–
7.46 (4H, m), 7.11–7,02 (2H, t), 2.54 (3H, s); 13C NMR (CDCl3, 50 MHz) d 197.68,
165.56, 160.63, 144.79, 136.12, 135.98, 129.08, 128.92, 127.14, 116.20, 115.77,
26.68. GC–MS: m/z = 171, 199, 214. 4-Methylbiphenyl: White solid. 1H NMR
(200 MHz, CDCl3) d 7.59 (2H, d), 7.49 (2H, d), 7.40 (2H, dd), 7.34 (1H, d), 7.28
(2H, d), 2.46 (3H, s); 13C NMR (50 MHz, CDCl3) d 141.31, 138.51, 137.14, 129.78,
129.61, 128.84, 127.30, 127.10, 21.22; GC–MS: m/z = 152, 168. 5-
Phenylpyrimidine: White solid. 1H NMR (CDCl3, 200 MHz) d 9.16 (1H, s), 8.90
(1H, s), 7.52–7,47 (5H, m); 13C NMR (CDCl3, 50 MHz) d 157.31, 154.72, 134.15,
129.32, 128.93, 126.80. GC–MS: m/z = 102, 129, 156.
We can conclude that the set with Pd2(dba)3 0.01%, PEG 300,
K2CO3 at thermal conditions with a temperature of 55 °C works
better for aryl–aryl than heteroaryl–aryl couplings in Suzuki reac-
tions. The use of small Pd amounts resulting in good yields of iso-
lated products after a simple workup must be underlined as the
main advantage of the proposed system.
Acknowledgments
Financial support from CNPq, CAPES, FAPERJ, and FUJB is
acknowledged.
References and notes
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Lautens, M. Org. Lett. 2005, 7, 4745–4747; (d) Senra, J. D.; Malta, L. F. B.; Souza,
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