Carbon−Carbon Coupling Reactions Catalyzed by Heterogeneous ...

Heterogeneous Pd Catalyzed C−C Coupling Reactions Chemical Reviews, 2007, Vol. 107, No. 1 137
to the original support (re-deposition) but also to other
supports added to the mixture, or the dissolved species can
precipitate as free Pd particles. 38 Naturally the re-deposited
Pd exhibits different properties due to crystallite growth as
compared with the starting Pd system, and thus normally
the catalytic activity drops after each run when the material
is used several times. 28,50 As another effect, re-deposited Pd
can catalyze unwanted side reactions, while only the dissolved
Pd supports the envisaged cross-coupling. 11,28
2. Suzuki Reactions
2.1. Pd on Carbon (Pd/C)
The Suzuki-Miyaura reaction has become a mainstay of
modern synthetic organic chemistry for the preparation of
biaryl compounds. 89-91 In the past decade, the Pd/C-catalyzed
arylation by Suzuki-Miyaura reaction has been applied
widely in organic synthesis of biaryl compounds, which can
also be heterocyclic. It can further be used in coupling of
various organic moieties different from aryl compounds, such
as alkenes, alkynes, or alkanes. The first example of Pd/Ccatalyzed
Suzuki reaction was reported by Marck and coworkers
in 1994. 92 In general, Pd/C is used with or without
additional phosphine ligands, and often the application of
aqueous solvents is advantageous.
2.1.1. In the Presence of Phosphine Ligands
In the first examples of the application of Pd/C in Suzuki-
Miyaura couplings (Scheme 2), triphenylphosphine was used
as a ligand adopting the methodology from homogeneous
catalysis. 3 The bromoarene 1 and the triflate 3 were
transformed into the corresponding diaryl products 2 and 4
in high yields. 92
Scheme 2. Pd/C-Catalyzed Suzuki Coupling in the Presence
of PPh3
Nishida and co-workers 59 found that a phosphine ligand
was indispensable for the Pd/C-catalyzed Suzuki reactions
of halopyridines and haloquinolines in most cases (Table 1).
The reactions of bromopyridines 5a-c, 2-chloropyridine
(5g), 2-chloropyridines with an electron-withdrawing group
5d-f, 5h, and 5i, and haloquinoline 7a and 7b proceeded
smoothly and gave the products in good yields (Table 1,
entries 1-9, 14, 15, and 17). However, the reactions of
2-chloropyridines with an electron-donating group, 5j and
5k, gave unsatisfactory results (Table 1, entries 10 and 11).
The reactivity of the substrate showed the same tendency as
was seen in the reaction with a homogeneous catalyst; that
is, chloropyridines with an electron-withdrawing group were
more reactive than those with an electron-donating group.
In order to improve the yields of less-reactive substrates
such as 3-chloropyridine (5l), 4-chloropyridine (5m), and
6-chloroquinoline (7c), ligand effects were studied by using
Table 1. Pd/C-Catalyzed Suzuki Coupling of N-Heterocycles 5,
7, or 8 with PPh3
entry haloheterocycle ligand yield a (%)
1 5a: R) H, X ) 2-Br PPh3 85
2 5b: R) H, X ) 3-Br PPh3 90
3 5c: R) H, X ) 4-Br b PPh3 60
4 5d: R) 3-NO2,X) 2-Cl PPh3 94
5 5e: R) 5-CN, X ) 2-Cl PPh3 90
6 5f: R) 5- NO2,X) 2-Cl PPh3 85
7 5g: R) H, X ) 2-Cl none 0
PPh3 82
8 5h: R) 3-CN, X ) 2-Cl none 16
PPh3 100
9 5i: R) 5-CF3,X) 2-Cl none 30
PPh3 85
10 5j: R) 6-OMe, X ) 2-Cl PPh3 25
11 5k: R) 3-NH2,X) 2-Cl PPh3 19
12 5l: R) H, X ) 3-Cl PPh3 2
13 5m: R) H, X ) 4-Clb PPh3 9
14 7a: X) 2-Cl none 0
PPh3 91
15 7b: X) 3-Br none 0
PPh3 91
16 7c: X) 6-Cl PPh3 0
17 8 none 36
PPh3 72
a Isolated yield. b Pyridinium hydrochloride was used.
3-chloropyridine (5l) and Pd/C. The sterically hindered
2-(dicyclohexylphosphino)biphenyl 12 (9 mol %) was found
to improve the yield dramatically (Table 2, compare entries
1 and 3). 59,93 It has been reported that bulky and electronrich
ligands increase the yields of homogeneous Suzuki-
Miyaura and other coupling reactions. 91 These ligands
facilitate oxidative addition, and the spatial bulk around the
metal promotes reductive elimination. Thus, during the Pd/
C-catalyzed reaction, 12 would interact with the leaching
Pd and show the same effects. The combination of Pd/C and
12 was also effective for the reactions of 4-chloropyridine
5m and 6-chloroquinoline 7c (Table 2, entries 4 and 5). 59
Remarkably, this combination was not effective in the
reaction of 4-methoxychlorobenzene 11, but Pd(II)/C and
12 provided high yields of the product. (Table 2, entry 6).
Table 2. Pd/C-Catalyzed Suzuki Coupling of N-Heterocycles 5,
7c, or 4-Methoxychlorobenzene, 11, with Different Ligands
entry haloheterocycle ligand yielda (%)
1 5l: R) H, X ) 3-Cl dppp 0
2 5l: R) H, X ) 3-Cl dppb 0
3 5l: R) H, X ) 3-Cl 12 88
4 5m: R) H, X ) 4-Cl 12 92
5 7c: X) 6-Cl 12 77
6 11 12 80b a Isolated yield. b Pd(II)/C was used.