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L. Chen et al. / Journal of Organometallic Chemistry 695 (2010) 1768e1775
Table 1
The reasons for the particular efficiency of 2 as a ligand are
not clear to us. However, according to the previously reported
biaryl phosphine ligands [36], and the well-documented depro-
tonation of indene by base [19], we suggest two reasons: (1) the
structure of 2 is similar to that of the reported biaryl phosphines;
(2) the reaction of 2 with tBuONa in DME can generate the anionic
ligand in situ, and the strong electron-donor ability of the indene
anion may increase the electron density at the phosphorus and
improve the reaction rate as a result. To provide support for this
finding, we undertook a series of 31P NMR studies. When one
equivalent of tBuONa was added to a solution of phosphonium salt
in DME, the resonance for the phosphonium salt disappeared, and
Selected bond distances (Å) and angles (ꢀ) for compound 2.
C(7)eC(8)
C(7)eC(15)
C(8)eP(1)
1.364(4)
1.501(5)
1.781(3)
C(16)eP(1)
C(22)eP(1)
C(1)eC(7)
1.804(3)
1.811(3)
1.469(5)
C(8)eC(7)eC(1)
C(7)eC(8)eP(1)
C(9)eC(8)eP(1)
129.4(3)
126.9(3)
122.8(2)
C(8)eC(7)eC(15)
C(8)eP(1)eC(16)
C(8)eP(1)eC(22)
108.7(3)
109.77(15)
110.46(15)
(Table 3, entries 5 and 6). Similar results were obtained when aryl
amine was used as a replacement for morpholine (Table 3, entries
7e13).
a new signal appeared (
d
ꢁ17.17 ppm), corresponding to phos-
Besides aryl chloride, the scope of the Pd/(2-phenylindenyl)
dicyclohexylphosphine catalytic system can be extended to heter-
oaryl halide. For example, the amination of 2-chloropyridine with
morpholine in DME gave the coupled product in 94% yield, while
the reaction of 2-chloropyridine with octyl amime, aniline or ortho-
toluidine afforded the corresponding products in moderate yield
(Table 4, entries 1, 3, 4). Reactions of heteroaryl bromide with
amines were faster than reactions of heteroaryl chloride. For
instance, morpholine reacted with 2-bromopyridine in 12 h to give
the desired product in 97% yield (Table 4, entry 6). Octyl amine,
aniline and ortho-toluidine formed the coupled products in
acceptable yield in 12 h (Table 4, entries 5, 7, 8).
phine. When 4.0 equiv tBuONa was added to the phosphonium
salt in DME it gave a red solution immediately, the resonance for
the phosphonium salt disappeared, and another new signal
appeared (
d
ꢁ13.15 ppm), corresponding to anionic phosphine.
The results from the calculations were consistent with the
experimental results, since the resonance for the anionic phos-
phine appeared between that of the phosphonium salt 2 and 1
(Scheme 2, Table 7). Work is in progress in our laboratory with the
aim of demonstrating the anionic effect of this ligand on the
catalytic activity.
The reaction conditions optimized for the amination of aryl
chlorides were also effective for the amination of aryl bromides.
Generally, the rates for amination of aryl bromide were faster than
those for amination of aryl chlorides. For instance, phenyl bromide
was readily aminated with the Pd(dba)2/2 catalyst system, and the
reactions were completed in 5 h (Table 5, entries 1e4). We also
found that it was possible to efficiently couple sterically hindered
2-bromomesitylene with a variety of amines (Table 5, entries 5, 7
and 8).
Although more reactive, aryl iodides usually provide lower
yields than their bromide counterparts in such reactions
[16,31,32], the reason being that the iodide is inhibiting the
reaction by binding to a Pd(II) intermediate and forming a Pd ate
complex [33]. Only a few groups have reported an efficient
procedure for the coupling of aryl iodides with amines using
phosphine ligands [15,34,35]. Recently, Buchwald’s group reported
that reactions were smothered when DME was the solvent [33],
while we found that the Pd(dba)2/(2-phenylindenyl)dicyclohex-
ylphosphine catalyst system, in combination with DME as the
solvent, allowed phenyl iodide to couple successfully with amines
in 5 h (Table 6).
3. Conclusion
In summary, we synthesized 2-phenylindenyl phosphine ligand.
This ligand can be changed into anionic phosphine ligand in situ
and utilized in the palladium-catalyzed Buchwald/Hartwig ami-
nation reactions in DME, providing good to excellent yields of
amination products from aryl chlorides, bromides and iodides. 31P
NMR studies show that the resonance for the anionic phosphine
appeared between those of the (2-phenylindenyl)-dicyclohexyl
phosphonium salt and (2-phenylindenyl)dicyclohexylphosphine.
The calculated results were consistent with the experimental
results.
4. Experimental section
4.1. General considerations
Unless otherwise noted, all reagents were purchased from
commercial suppliers and used without purification. All Buchwald/
Hartwig amination reactions were performed in resealable screw
cap Schlenk flask (approx. 20 mL volume) in the presence of Teflon-
coated magnetic stirrer bar (3 mm ꢂ 10 mm). Toluene and DME
were distilled from sodium benzophenone ketyl under nitrogen.
Most commercially available amines were used as received. Some
amines may require distillation depending on the conditions.
tBuONa were purchased from Fluka. Silica gel (Merk, 70e230 and
230e400 mesh) was used for column chromatography. 1H NMR
spectra were recorded on a Mercury-Plus (400 MHz or 600 MHz)
spectrometer. Spectra were referenced internally to the residual
Table 2
Screen of Pd Sources and solvents for the coupling of phenyl chloride and aniline.a
1% Pd
H2N
Cl
+
2% Ligand
N
H
proton resonance in CDCl3
(TMS, 0.00 ppm) as the internal standard. Chemical shifts (
reported as part per million (ppm) in scale downfield from TMS.
13C NMR spectra were referenced to CDCl3 (
77.0 ppm, the middle
(
d
7.26 ppm), or with tetramethylsilane
Entry
Pd source
Solvent
T (ꢀC)
Time [h]
Yieldb (%)
d
d) were
1
2
3
4
5
6
7
8
Pd(dba)2
Pd(OAc)2
PdCl2(CH3CN)2
Pd(dba)2
Pd(OAc)2
PdCl2(CH3CN)2
Pd(dba)2
Toluene
Toluene
Toluene
DME
DME
DME
120
120
120
120
120
120
80
12
12
12
2
2
2
92
11
65
98
21
98
51
34
d
d
peak). 31P NMR spectra were referenced to 85% H3PO4 externally.
Coupling constants (J) were reported in Hertz (Hz). Mass spectra
(EI-MS) were recorded on a HP 5989B Mass Spectrometer. The
products described in GC yield were accorded to the authentic
samples/dodecane calibration standard from Agilent 6890 GC
system. All yields reported refer to isolated yield of compounds
estimated to be greater than 95% purity as determined by capillary
DME
DME
1
1
PdCl2(CH3CN)2
80
a
ArCl (1 mmol), aniline (1.2 mmol), Pd (1 mol%), ligand (2 mol%), tBuONa
(1.4 mmol), solvent (4 mL).
b
GC yields.