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J. Yorke et al. / Tetrahedron Letters 48 (2007) 8843–8845
Table 1. Solvent and base effecta
Ru complex, Pd(OAc)2
MeO
MeO
Br
+
Ph
Base, Solvent
Ph
Entry
Solvent
Base
Temperature (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
THF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOAc
K3PO4
Cy2NMe
K2CO3
NaOAc
K3PO4
Cy2NMe
100
100
130
130
130
130
130
130
130
130
130
130
43
46
46
88
90
52
89
56
94
56
94
79
Dioxane
Toluene
DMF
DMA
DMA
DMA
DMA
NMP
NMP
NMP
NMP
10
11
12
a 1.0 mmol p-bromoanisole, 1.5 mmol styrene, 2.0 mmol base, 0.010 mmol Pd(OAc)2, 0.010 mmol (tBu2dp)RuCp*, 1 mL solvent, 18 h.
b GC yields of trans-methoxystilbene using
1 mol % Pd(OAc)2 loading, the yields of trans-4-methoxy-
stilbene were excellent in polar aprotic solvents such
as dimethylformamide (DMF), dimethylacetamide
(DMA) and N-methylpyrrolidone (NMP), with NMP
giving the highest yield (entry 9). The yields were much
lower in less polar solvents such as toluene, tetrahydro-
furan (THF) and dioxane (entries 1–3). For safety concern,
the operation temperature was set at 100 °C for the latter
two solvents as they have relatively lower boiling points.
The bases also affected the yield significantly. In both
DMA and NMP, K2CO3 and K3PO4 gave comparable
yields that were better than NaOAc and Cy2NMe. Thus
we decided to use NMP as the solvent and K2CO3 as the
base for subsequent investigations.
Pd(OAc)2 loading, the yield was 99% with the (tBu2dp)-
RuCp* (entry 15), but only 11% without any ruthenium
complex (entry 17). While the two ruthenium complexes
gave comparable yields for the coupling of aryl bro-
mides, (tBu2dp)RuCp* was more efficient in the cou-
pling of aryl chlorides than its phenyl analogue. For
example, at 1 mol % Pd(OAc)2 loading, (tBu2dp)RuCp*
gave a complete conversion of p-chloronitrobenzene,
but (Ph2dp)RuCp* gave only a 44% yield (entry 16).
The better efficiency of the tert-butyl complex over its
phenyl analogue is likely due to its larger steric
bulkiness.
While the palladium complexes based on the ruthenium
complex-ligands were effective in the coupling of bro-
mides and selected activated chloride (e.g., p-chloro-
nitrobenzene), they were not effective in the coupling of
neutral and deactivated chloride such as p-chloroanisole
(entries 20–23). This is in sharp contrast to PtBu3, which
is highly efficient in the coupling of deactivated aryl
chlorides.11 This may be contributed to the steric factor
since the planar sp2-phosphorus based 1,2,4-phospho-
lide ligands are not as hindered as the tetrahedral
sp3-phosphorus based PtBu3. As the sp2-phosphorus
species are stronger p-acceptors towards low-valent
transition metals than tertiary phosphanes,2 the ruthe-
nium complexes with sp2-phosphorus atoms may engage
in back-bonding with palladium in a fashion similar to
phosphites and phosphinites, which have been success-
fully applied in the Heck reaction.12,13
To evaluate the efficiency of the ruthenium complexes as
ligands, we selected several aryl bromides and chlorides,
which are generally harder to couple than corresponding
iodides. The choices can be divided into activated,
neutral and deactivated bromides and chlorides. First,
we studied the coupling of 40-bromoacetophenone, an
activated aryl bromide, and styrene with 0.1 mol % load-
ing of Pd(OAc)2 and the ruthenium complex. Both
ruthenium complexes led to complete conversion of
the bromides and excellent yields of trans-4-acetylstil-
bene (Table 2, entries 1 and 2). It was not surprising
as in some reports, 40-bromoacetophenone had been
coupled to styrene in the absence of any ligand.10 Indeed
in our test, even without any ruthenium complex, the
conversion of this bromide was complete (entry 3).
However, when we used bromobenzene, p-bromoani-
sole, 40-chloroacetophenone and p-chloronitrobenzene
as the substrate, the systems with the ruthenium com-
plexes gave much higher yields than the ligand free sys-
tems, indicating that the ruthenium complexes were
essential in the coupling reactions of less reactive aryl
halides. For example, with 0.1 mol % Pd(OAc)2 loading
for the coupling of p-bromoanisole, the yields were
around 70% with the ruthenium complexes and 30%
without them (entries 7–9). The difference was more pro-
nounced when aryl chlorides were used as the substrates.
In the case of p-chloronitrobenzene, at 1 mol %
In summary, we demonstrated that the ruthenium com-
plexes based on g5-1,2,4-diazaphospholide groups with
an sp2-hybridized phosphorus atoms can act as efficient
ligands in the Heck reaction, in which the ruthenium
complexes are likely to act as two-electron-donor
ligands g1-bonded to the palladium ion through the
phosphorus-atom lone pair.4,14 This is the first applica-
tion of sp2-hybridized phosphorus ligands in the Heck
reaction. The results suggest that the metal complexes
containing sp2-hybridized phosphorus atoms are viable
ligands in organometallic synthesis and catalysis.