7614
A. Scrivanti et al. / Tetrahedron 65 (2009) 7611–7615
identified by their GC–MS and 1H NMR. 1H NMR spectra (CDCl3)
Table 5
Coupling of phenylboronic acid with aryl chloridesa
were recorded on a Bruker Avance 300 spectrometer operating at
300.11 MHz. GC–MS spectra were obtained with a HP 5890 series II
gas chromatograph interfaced to a HP 5971 quadrupole mass de-
tector. The catalytic reactions were monitored by GLC on an Agilent
Technologies 6850 gas chromatograph.
3
B(OH)2
+
Ar
Ar Cl
K2CO3
ArCl/3
Entry
1
ArCl
Conv. [%]b
100
TONc
1000
O
O
O
4.2. General procedure for coupling reactions
1000
3000
Cl
Cl
Cl
In a typical experiment (entry 6 of Table 1), a 50 mL glass reactor
was charged with 4-bromoacetophenone (0.80 g, 4.0 mmol),
phenylboronic acid (0.73 g, 6.0 mmol), K2CO3 (1.10 g, 8.0 mmol), n-
undecane (0.16 g, 1.0 mmol, as the gas chromatographic internal
2
96
2880
3
4
5
5000
1000
1000
75
53
28
3750
530
standard) and 12 mL of toluene. To the resulting suspension 100 mL
of a 1.0ꢂ10ꢁ4 mol/L solution of complex 3 in toluene were added
and the mixture was heated under magnetic stirring at 110 ꢀC for
2 h. After cooling to room temperature and filtration on Celite, the
raw reaction mixture was analyzed by GLC.
Cl
Cl
Cl
280
O
6
1000
17
170
References and notes
a
Reaction conditions: solvent: toluene (12 mL); T: 110 ꢀC; t: 2 h; ArCl: 4.0 mmol;
phenylboronic acid: 6.0 mmol; K2CO3: 8.0 mmol; acid/ArCl¼1.5:1; base/ArCl¼2:1.
1. Recent reviews: (a) Miyaura, N. In Metal-Catalyzed Cross-Coupling reactions;
2nd ed.; de Mejere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004;
Chapter 2; (b) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419; (c) Corbet,
J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651; (d) Phan, N. T. S.; Van Der Sluys,
M.; Jones, C. W. Adv. Synth. Catal. 2006, 348, 609; (e) Yin, L.; Liebscher, J. Chem.
Rev. 2007, 107, 133; (f) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275; (g)
Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461; (h) Alonso, F.;
Beletskaya, I. P.; Yus, M. Tetrahedron 2008, 64, 3047.
b
By GLC with n-undecane as internal standard.
c
Mol of ArCl converted/mol of catalyst.
In contrast with that found with aryl bromides, the presence
of EDG in para position on the aryl chloride significantly in-
fluences the catalysis leading to reduced reaction rates. This effect
suggests that with aryl chlorides the oxidative addition of the
substrate to the metal centre is the rate determining step in the
catalytic cycle.
¨
2. Beller, M.; Fischer, H.; Herrmann, W. A.; Ofele, K.; Brossmer, C. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1848.
3. For selected references, see: (a) Bedford, R. B.; Hazelwood (ne´e Welch), S. L.;
Horton, P. N.; Hursthouse, M. B. Dalton Trans. 2003, 4164; (b) Albisson, D. A.;
Bedford, R. B.; Lawrence, S. E.; Noelle Scully, P. Chem. Commun. 1998, 2095; (c)
Bedford, R. B.; Welch, S. L. Chem. Commun. 2001, 129; (d) Bedford, R. B.; Ha-
zelwood (ne´e Welch), S. L.; Limmert, M. E.; Albisson, D. A.; Draper, S. M.; Noelle
Scully, P.; Coles, S. J.; Hursthouse, M. B. Chem.dEur. J. 2003, 9, 3216; (e) Ine´s, B.;
3. Conclusions
´
SanMartin, R.; Churruca, F.; Domınguez, E.; Urtiaga, M. K.; Arriortua, M. I. Or-
ganometallics 2008, 27, 2833; (f) Kondolff, I.; Feuerstein, M.; Doucet, H.; Santelli,
M. Tetrahedron 2007, 63, 9514.
4. For reviews on the Pd-catalyzed couplings of aryl chlorides see: (a) Littke, A. F.;
Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176; (b) Bedford, R. B.; Cazin, C. S. J.;
Holder, D. Coord. Chem. Rev. 2004, 248, 2283.
In summary, complex 3 is a highly efficient catalyst for the
Suzuki–Miyaura coupling. The reaction can be carried out in tol-
uene using inexpensive bases such as K2CO3 or K3PO4. With aryl
bromides very high TOF numbers can be obtained and, in-
terestingly, the presence of EDG on the substrate does not affect
the reaction rate. At variance, the catalytic activity decreases sig-
nificantly with aryl bromides bearing bulky substituents; however,
the catalyst is so efficient that the coupling of 2-bromo-1,3,5-tri-
methylbenzene with phenylboronic acid can be carried out with
quantitative yield using 0.02 mol % in only two hours. Lower re-
action rates are obtained with aryl chlorides, but still the catalyst
activity is excellent. In contrast with that found with aryl bro-
mides, the presence of EDG in para position of the aryl chlorides
leads to significantly reduced reaction rates. By comparison with
the most active catalysts it appears that 3 suffers of some limita-
tions in particular when hindered substrates are used. We are
prone to attribute this weakness to the stiffness of the 8-oxy-
quinoline moiety, future work to improve the ligand design is
planned.
5. For selected references, see: (a) Bedford, R. B.; Cazin, C. S. J.; Hazelwood (ne´e
Welch), S. L. Angew. Chem., Int. Ed. 2002, 41, 4120; (b) Bedford, R. B.; Hazelwood
(ne´e Welch), S. L.; Limmert, M. E. Chem. Commun. 2002, 2610; (c) Schneider, S.
K.; Roembke, P.; Julius, G. R.; Raubenheimer, H. G.; Herrmann, W. A. Adv. Synth.
Catal. 2006, 348, 1862; (d) Zapft, A.; Ehrentraut, A.; Beller, M. Angew. Chem.,
Int. Ed. 2000, 39, 4153; (e) Zapft, A.; Jackstell, R.; Rataboul, F.; Riermeier, T.;
Monsees, A.; Furhmann, C.; Shaikh, N.; Dingerdissen, U.; Beller, M. Chem.
Commun. 2004, 38; (f) Colacot, T. J.; Shea, H. A. Org. Lett. 2004, 6, 3731; (g) So,
C. M.; Lau, C. P.; Kwong, F. Y. Org. Lett. 2007, 9, 2795; (h) Fleckenstein, C. A.;
Plenio, H. Organometallics 2007, 26, 2758; (i) Cui, M.; Li, J.; Yu, A.; Zhang, J.;
Wu, Y. J. Mol. Catal. A: Chem. 2008, 290, 67.
6. For selected references, see: (a) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.;
Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101; (b) Navarro, O.; Kelly,
R. A.; Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 16194; (c) Barder, T. E.; Walker, S.
D.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685 and ref-
erences therein; (d) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122,
4020; (e) Liu, S.-Y.; Choi, M. J.; Fu, G. C. Chem. Commun. 2001, 2408; (f)
Gsto¨ttmayr, C. W. K.; Bo¨hm, V. P. W.; Herdtweck, E.; Grosche, M.; Herrmann, W.
A. Angew. Chem., Int. Ed. 2002, 41, 1363.
7. For selected references, see: (a) Billingsley, K.; Buchwald, S. L. J. Am. Chem. Soc.
2007, 129, 3358 and references therein; (b) Li, F.; Hor, T. S. A. Adv. Synth. Catal.
2008, 350, 2391; (c) So, C. M.; Yeung, C. C.; Lau, C. P.; Kwong, F. Y. J. Org. Chem.
2008, 73, 7803; (d) Kondolff, I.; Doucet, H.; Santelli, M. J. Mol. Catal. A: Chem.
2007, 269, 110.
4. Experimental
8. A recent review on the use of bidentate P,O ligands: Kwong, F. Y.; Chan, A. S. C.
Synlett 2008, 1440.
4.1. General materials and methods
9. A recent review on the use of hemilabile ligands: Weng, Z.; Teo, S.; Hor, T. S. A.
Acc. Chem. Res. 2007, 40, 676.
The catalytic experiments were carried out under argon atmo-
sphere using standard Schlenk techniques, unless otherwise stated.
Toluene was distilled over sodium/benzophenone under argon and
immediately used. DMF and NMP were purified as described in the
literature.17 Bromobenzene (Aldrich) was distilled immediately
before the use, the other aryl halides were high purity commercial
products (Aldrich) and were used as received. Complex 3 was
prepared as described previously.16 The coupling products were
10. Recent examples of bidentate P, O ligands employed in Suzuki reaction: (a) Dai,
W.-M.; Li, Y. N.; Zhang, Y.; Yue, C. Y.; Wu, J. L. Chem.dEur. J. 2008, 14, 5538; (b)
Venkateswaran, R.; Balakrishna, M. S.; Mobin, S. M. Eur. J. Inorg. Chem. 2007,
1930; (c) Singh, G.; Bali, S.; Singh, A. K. Polyhedron 2007, 26, 897; (d) Teo, S.;
Weng, Z.; Hor, T. S. A. Organometallics 2006, 25, 1199.
11. Recent examples of bidentate P,N ligands employed in Suzuki reaction: (a)
Chiang, W. Y.; Hong, F. E. J. Organomet. Chem. 2009, 694, 1473; (b) Yu, S. B.; Hu,
X. P.; Deng, J.; Huang, J. D.; Wang, D. Y.; Duan, Z. C.; Zheng, Z. Tetrahedron Lett.
2008, 49, 1253; (c) Kingston, J. V.; Verkade, J. G. J. Org. Chem. 2007, 72, 2816; (d)