To evaluate the scope and limitations of this procedure,
the reaction of a wide variety of aryl halides with phenyl-
boronic acid was examined using palladacycle 1 in DMF
room temperature reported to date.18 Moreover, these reac-
tions can be performed in air without the need of any special
experimental precautions, rendering this method highly
attractive for synthetic purposes.
3 4
and K PO as a base (Table 2).
Palladacycle 1 also efficiently promotes the cross-coupling
1
9
of sterically demanding substrates. Thus, the reaction of
-bromomesitylene with 2-tolylboronic acid over 14 h at 130
°C affords 2,2′,4,6-tetramethylbiphenyl in 65% isolated yield
2
Table 2. Palladacycle 1 Catalyzed Suzuki Cross-Coupling of
Aryl Halides and Phenylboronic Acida
(Scheme 1).
entry
ArX
1 (%)
T (°C)
t (h)
yield (%)b
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
2,5-Me2C6H4Br
4-MeOC6H4Br
4-MeOC6H4Br
4-PhC6H4Br
1-naphthylBr
2-naphthylBr
4-CF3C6H4Br
3-CF3C6H4Br
2-CF3C6H4Br
4-O2NC6H4Br
4-O2NC6H4Br
4-AcC6H4Br
4-MeOC6H4I
4-AcC6H4Cl
4-NCC6H4Cl
4-NCC6H4Cl
4-O2NC6H4Cl
4-O2NC6H4Cl
PhCl
0.2
0.5
0.5
0.2
0.2
0.5
0.2
0.2
0.2
0.2
0.5
0.2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2
25
130
25
130
130
25
130
130
130
130
25
130
25
130
130
25
130
25
130
130
130
130
38
4
38
2
4
38
2
2
2
2
16
2
38
4
4
16
4
16
22
18
21
21
94
90
95
99
97
95
98
97
93
92
98
97
93
92
90
92
93
95
46c
40
29c
13c
Scheme 1. Suzuki Cross-Coupling of Sterically Demanding
Substrates
1
1
1
1
1
1
1
1
1
1
2
2
2
To gain some insight into the reaction mechanism, a
preliminary competitive experiment was performed. A
mixture of 0.002 mmol of 1, 0.2 mmol of each aryl bromide
(
4-bromoanisol, 4-bromotoluene, bromobenzene, 4-bromo-
biphenyl, and 4-acetylbromobenzene), 5 mmol of PhB(OH)
and 2 mmol of K PO in 4 mL of DMF was heated at 80 °C
2
,
3
4
for 1 h. The biaryls 4-methoxybiphenyl, biphenyl, triphenyl,
and 4-acetylbiphenyl were obtained in the ratio of 1:1.6:8.7:
0:50.6, respectively. This behavior, i.e., electron-withdraw-
1-naphthylCl
4-MeC6H4Cl
4-MeOC6H4Cl
2
2
1
ing substituents on the aryl bromide increasing the reaction
rate, is analogous to those already reported for other
a
Reaction conditions: 1 mmol of ArX, 1.5 equiv of PhB(OH)2, 2 equiv
of K3PO4, 0.2 equiv of NBu4Br, 5 mL of DMF. Isolated yields average
of two runs. GC yield.
b
12a
20
palladium and nickel catalyst precursors. A detailed study
on the mechanism of this reaction is underway in our
laboratory and will published in due course.
c
In summary, these results clearly demonstrate that for a
wide range of aryl halides the Suzuki coupling, at room
temperature, can be readily promoted by palladacycle 1.
Moreover, these results illustrate the high versatility of
cyclopalladated compounds (in particular, sulfur-containing
It is clear from Table 2 that both electron-rich and -poor
aryl bromides are efficiently coupled in the presence of 1 to
provide the corresponding biaryl products in excellent
isolated yields (>90%), and a wide variety of functional
groups are tolerated (nitro, acetyl, cyano, etc.). Moreover,
palladacycle 1 promotes the Suzuki coupling even at room
temperature although longer reactions times were necessary
21
palladacycles) as catalyst precursors for C-C bond-forming
2
2
reactions.
(
compare, for example, entries 2 and 3, Table 2). Only with
(
18) Until now only palladium complexes associated with electron-rich
reactions involving electron-neutral and -rich aryl chlorides
are low conversions achieved even at higher reaction
temperatures (entries 19-22, Table 2). Lower reaction times
were necessary in the case of electron-poor aryl bromides
and bulky phosphine efficiently promote the cross-coupling at room
temperature (for unactivated aryl chlorides see refs 4 and 5; for activated
aryl chlorides see ref 6). For the coupling of aryl iodides and aryl bromides
at room temperature, see: (a) Campi, E. M.; Jackson, W. R.; Marcuccio,
S. M.; Naesland, C. G. M. J. Chem. Soc., Chem. Commun. 1994, 2395. (b)
Anderson, J. C.; Namli, H.; Roberts, C. A. Tetrahedron 1997, 53, 15123.
c) Uenishi, J.-i.; Beau, J.-M.; Armstrong, R. W.; Kishi, Y. J. Am. Chem.
Soc. 1987, 109, 4756. (d) Johnson, C. R.; Johns, B. A. Synlett 1997, 53,
15123. (e) Bumagin, N. A.; Bykov, V. V. Tetrahedron 1997, 53, 14437.
(
∼2 h) compared with electron-rich aryl bromides (∼4 h).
(
An ortho-CF -substitued aryl bromide (entry 9, Table 2) gave
3
slightly lower yields compared with its meta- and para-
substituted analogues (entries 8 and 7, Table 2). Cross-
couplings of electron-poor aryl chlorides also gave excellent
yields in the corresponding biaryl products (entries 13-18,
Table 2).
(
f) Katamani, A.; Overman, L. E. J. Org. Chem. 1999, 64, 8743. (h) Uozumi,
Y.; Danjo, H.; Hayashi, T. J. Org. Chem. 1999, 64, 3384. (g) Bussolari, J.
C.; Rehborn, D. C. Org. Lett. 1999, 1, 965.
(19) For the cross-coupling of sterically hindered halo-arenes, see for
example ref 2b.
(20) Saito, S.; Oh-tani, S.; Miyaura, N. J. Org. Chem. 1997, 62, 8024.
(
21) For the synthesis and applications of sulfur-containing palladacycles,
Note that except for electron-neutral and -rich aryl
chlorides the reaction proceeds to completion at room
temperature, producing the bis-aryls in >90% isolated yields.
Palladacycle 1 is, therefore, the most efficient phosphine-
free palladium catalyst precursor for the Suzuki coupling at
see, for example: (a) Spencer, J.; Pfeffer, M.; Kyritsakas, N.; Fischer, J.
Organometallics 1995, 14, 2214. (b) Dupont, J.; Basso, N. R.; Meneghetti,
M. R.; Konrath, R. A.; Burrow, R.; Horner, M. Organometallics 1997, 16,
386. (c) Dupont, J.; Basso, N. R.; Meneghetti, M. R. Polyhedron 1996,
5, 2299. (d) Alb e´ niz, A. C.; Espinet, P.; Kin, Y.-S. Organometallics 1996,
2
1
15, 5010.
Org. Lett., Vol. 2, No. 18, 2000
2883