concerning the Suzuki-Miyaura reaction involve the use of
halogenated or sulfonated electrophiles (iodide, bromide,
chloride, or triflate). However, it has been reported that
arenediazonium salts are also effective electrophiles in
Table 2. Cross-Coupling of Arenediazonium Salts
5
palladium cross-coupling reactions. Surprisingly, only a few
6
reports have described their use for the Suzuki-Miyaura
7
coupling since the pioneering work of the Genet and
8
Sengupta groups. From an industrial point of view, diazo-
nium electrophiles, readily prepared from inexpensive anilines,
compete favorably with less reactive and more expensive
halogenated electrophiles. In connection with our studies
9
related to the chemistry of Pd/C, we wish to disclose in
this paper our investigations concerning the cross-coupling
of arenediazonium salts with boronic acid partners under
ligandless and heterogeneous conditions.10
We initiated our optimization studies by selecting diazo-
nium salt 1a and phenyl boronic acid 2a as partners for the
Suzuki-Miyaura cross-coupling. We screened a variety of
technical grade solvents at moderate temperature (50 °C) and
with 5 mol % of Pd(0)/C as catalyst. The source of Pd(0)/C
used in this study is that commonly used for hydrogenation
and hydrogenolysis. The results compiled in Table 1 clearly
Table 1. Optimization Studies
a
entry
solvent
DME
DME/H2O
1,4-dioxane
i-PrOH
time (h)
yield (%)
1
2
3
4
5
6
12
2
12
2
2
0.5
15
47
3
91
84
92
EtOH
Ch3OH
a
Yields are an average of two runs.
highlight the beneficial effect of alcoholic solvents from
which methanol seems the most efficient in terms of yield
a Isolated yields are an average of two runs. b 1.7 equiv of diazonium
c
salt and 1 equiv of boronic acid were used. 1 equiv of diazonium salt and
1
.7 equiv of boronic acid were used. d Compound 3h decomposes rapidly
(
5) For a review, see: Roglans, A.; Pla-Quintana, A.; Moreno-Ma n˜ as,
M. Chem. ReV. 2006, 106, 4622-4643.
6) (a) Babudri, F.; Farinola, G. M.; Naso, F.; Panessa, D. J. Org. Chem.
on standing.
(
2
2
3
000, 65, 1554-1557. (b) Willis, D. M.; Strongin, R. M. Tetrahedron Lett.
000, 41, 6271-6274. (c) Andrus, M. B.; Song, C. Org. Lett. 2001, 3,
761-3764. (d) Selvakumar, K.; Zapf, A.; Spannenberg, A.; Beller, M.
and rate for the cross-coupling. Interestingly, while 1,4-
dioxane has been used successfully with homogeneous
catalysts, it gives only a sluggish reaction with Pd(0)/C. It
should be noted that the conditions developed do not require
the use of a base, resulting in a high chemoselectivity at the
Chem. Eur. J. 2002, 8, 3901-3906. (e) Frohn, H.-J.; Adonin, N. Y.; Bardin,
V. V.; Starichenko, V. F. J. Fluorine Chem. 2002, 117, 115-120. (f) Nelson,
M. L.; Ismail, M. Y.; McIntyre, L.; Bhatia, B.; Viski, P.; Hawkins, P.;
Rennie, G.; Andorsky, D.; Messersmith, D.; Stapleton, K.; Dumornay, J.;
Sheahan, P.; Verma, A. K.; Warchol, T.; Levy, S. B. J. Org. Chem. 2003,
7
6
8, 5838-5851. (g) Dai, M.; Liang, B.; Wang, C.; Chen, J.; Yang, Z. Org.
Lett. 2004, 6, 221-224. (h) Gallo, V.; Mastrorilli, P.; Nobile, C. F.; Paolillo,
R.; Taccardi, N. Eur. J. Inorg. Chem. 2005, 582-588.
(8) (a) Sengupta, S.; Bhattacharyya, S. J. Org. Chem. 1997, 62, 3405-
3406. (b) Sengupta, S.; Sadhukhan, S. K. Tetrahedron Lett. 1998, 39, 715-
718.
(9) (a) Felpin, F.-X.; Landais, Y. J. Org. Chem. 2005, 70, 6441-6446.
(b) Felpin, F.-X. J. Org. Chem. 2005, 70, 8575-8578. (c) Felpin, F.-X.;
Lory, C.; Sow, H.; Acherar, S. Tetrahedron 2007, 63, 3010-3016.
(10) Only a single example has been described independently by Genet
and Sengupta, see refs 7a and 8a.
(7) (a) Darses, S.; Jeffery, T.; Gen eˆ t, J. P.; Brayer, J. L.; Demoute, J. P.
Tetrahedron Lett. 1996, 37, 3857-3860. (b) Darses, S.; Jeffery, T.; Brayer,
J. L.; Demoute, J. P.; Gen eˆ t, J. P. Bull. Soc. Chim. Fr. 1996, 133, 1095-
1
102. (c) Darses, S.; Gen eˆ t, J. P.; Brayer, J. L.; Demoute, J. P. Tetrahedron
Lett. 1997, 38, 4393-4396. (d) Darses, S.; Michaud, G.; Gen eˆ t, J. P.
Tetrahedron Lett. 1998, 39, 5045-5048. (e) Darses, S.; Michaud, G.; Gen eˆ t,
J. P. Eur. J. Org. Chem. 1999, 1875-1883.
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