M. Beller et al.
In summary, a stable and
versatile palladium/imidazoli-
um–phosphane system has
been established for the cata-
lytic direct amination of aryl
halides with ammonia and sev-
eral primary as well as secon-
dary amines. A simple recy-
cling of this catalyst system has
been demonstrated. The active
catalyst is easily generated in
situ from the air- and water-
stable cationic imidazolium
Table 3. (Continued)
Entry
Aryl halide
Amine
Product
Yield[b]
[%]
19
47
[a] Reaction conditions: Aryl halide (1.0 mmol), Pd
amine (1.2 mmol), 1208C, 20 h. [b] Determined twice by gas chromatography with internal standard hexade-
cane. [c] 508C. [d] Room temp. [e] PdACHTUNTGRENNUG(OAc)2 (0.25 mol%), L2 (0.5 mol%). [f] without PdCAHTUNGTREN(NGUN OAc)2 and ligand.
[g] Yield of isolated product.
ACHTUNGRTEN(NUNG OAc)2 (1.0 mol%), L2 (2.0 mol%), NaOtBu (2.0 equiv),
cyclic amines are easily tolerated in this reaction (Table 3,
entries 1 and 2). Similar to the aminations with ammonia,
no diarylation was observed and only mono-arylated amines
were obtained showing the high chemoselectivity of the cat-
alyst system. In addition, no palladium black was formed
during the reaction. Investigating the reaction of 4-chloro-
quinaldine with morpholine more closely, we observed that
our catalyst system also allows for aminations at room tem-
perature giving the corresponding amine in 70% yield
(Table 3, entry 4). Furthermore, the catalyst loading is suc-
cessfully decreased to 0.25 mol% Pd without a significant
loss in productivity (Table 3, entry 5). Notably, product was
not observed without the addition of palladium and ligand.
Finally, we investigated the recycling of the cationic cata-
lyst system, similar to our previously reported procedure for
the palladium-catalyzed hydroxylation of aryl bromides.[22]
In these reactions we used the possibility of precipitating
the resulting amines just by adding hydrogen chloride,
whereas the catalyst remains in solution. After successful
conversion, the reaction solution was separated from the
precipitated product and just refilled in a new Schlenk flask,
in which only the substrates morpholine and 4-chloroquinal-
dine as well as the base were added. In this regard we were
able to run three consecutive aminations in yields in be-
tween 89–99% (Figure 1). This recycling strategy allows
reuse of the catalyst in a multiple batch reactor.
phosphanes and PdACTHNGUTERN(NUG OAc)2. In general, the catalytic amina-
tions of most substrates proceed without special precautions
in the presence of comparably low palladium loadings. Also,
room temperature amination are possible with this system.
Experimental Section
General: All reactions were performed under an inert nitrogen atmos-
phere (1–10 bar) by using an eightfold parallel autoclave. All starting ma-
terials as well as reactants were applied in the way as they were received
from commercial suppliers. Phosphane ligands were stored in Schlenk
flasks but scaled under air. Mass spectra were recorded on an AMD 402
double focusing, magnetic sector spectrometer (AMD Intectra). GCMS
spectra were recorded on a HP 5989 A (Hewlett Packard) chromato-
graph equipped with a quadropole analyzer. Gas chromatography analy-
ses were performed on a HP 6890 (Hewlett Packard) chromatograph
using a HP 5 column. All yields were determined by calibration of the
corresponding products (anilines, amines) with hexadecane as an internal
standard and analysis by using gas chromatography.
General procedure for the direct amination of aryl halides with ammo-
nia: A 3.0 mL autoclave was charged with ligand 2 (3.0 mg, 2.0 mol%)
and NaOtBu (38.4 mg, 2 equiv). The (hetero)aryl halide was also added
at this point, if it is a solid. In case of a liquid it was added at a later
point (see 4 lines below). The filled autoclave was placed into the auto-
clave device, evacuated, backfilled with argon, and then 0.2 mL of a Pd-
ACHUTNRGEN(NUG OAc)2-stock solution (5.0 mm PdCAHTUNGTNER(NUGN OAc)2 1,4-dioxane, 0.5 mol%) was
added and the mixture was stirred at room temperature for 10 min. Then,
(if liquid) the corresponding aryl halide (0.2 mmol) and a 0.5m NH3 solu-
tion (2.0 mL) in 1,4-dioxane (5.0 equiv NH3) were added successively
under an argon atmosphere. The reaction mixture was pressurized with
10 bar N2 and heated up to 1208C for 24 h. After the mixture had been
cooled to room temperature, it was laced with hexadecane (20 mL) as an
internal standard. The mixture was filtered and the yield was determined
by gas chromatography.
General procedure for the Buchwald–Hartwig amination of aryl halides:
A
15.0 mL ace pressure tube was charged with Pd
ACHTUNGRTENUN(NG OAc)2 (2.2 mg,
1.0 mol%), ligand (15.1 mg, 2.0 mol%) and NaOtBu (115.3 mg,
2
1.2 mmol). The filled ace pressure tube was evacuated and backfilled
with argon three times. Then the corresponding (hetero)aryl halide
(1.0 mmol), the amine (1.2 mmol), and 1,4-dioxane (2.0 mL) were added
successively under an argon atmosphere. The pressure tube was closed
and heated up to 1208C for 20 h. After the mixture had been cooled to
room temperature, it was laced with hexadecane (20 mL) as an internal
standard. The mixture was filtered and the yield was determined by gas
chromatography.
General procedure for the re-use of the catalyst in Buchwald–Hartwig-
Figure 1. Recycling experiment: amination of 4-chloroquinaldine with
aminations: The reaction was carried out to run in 25 mL Schlenk tubes,
morpholine. Reaction conditions: Aryl halide (1.0 mmol), Pd
G
added with PdACTHUGNTERNNU(G OAc)2 (2.2 mg, 1.0 mol%), ligand 2 (15.1 mg, 2.0 mol%)
(1.0 mol%), L2 (2.0 mol%), NaOtBu (1.2 equiv), amine (1.2 mmol),
1208C, 20 h. Determined by gas chromatography.
and NaOtBu (115.3 mg, 1.2 mmol). The filled Schlenk tube was evacuat-
ed and backfilled with argon three times. Then 4-chloroquinaldine
9602
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9599 – 9604