Pd-Catalyzed Amination of Aryl Halides with Ammonia
COMMUNICATION
tained, too, whereas a Pd/ligand ratio of 1:2 (Table 3, en-
tries 7 and 10) gives yields of around 70% under otherwise
identical reaction conditions. To our delight, 2-chlorostyrene
was converted to the corresponding 2-aminostyrene in good
yield (71%; Table 3, entry 12). As expected, the substitution
of bromide is preferred, if a bromide ligand competes with a
chloride ligand, and no significant amount Cl-substituted
product is formed (Table 3, entry 13; 68% yield). Notewor-
thy is that the reaction of the corresponding 1,2-dihalides se-
lectively yielded the monoaminated products in excellent
yields (Table 3, entries 14, 15; 89–99%). The activated 4-
bromobenzophenone (Table 3, entry 20; 80% yield) and de-
activated bromoarenes such as anisole, thioanisole, and N,N-
dimethylbenzene (Table 3, entries 16–18; 66–70% yield)
were also fully converted. The conversion of 2-bromoaniline
proceeded smoothly to give the corresponding 1,2-diamino-
benzene in 86% yield (Table 3, entry 19). Next, some N-het-
eroaryl bromides and chlorides were investigated.
Experimental Section
General: All reactions were performed under a nitrogen atmosphere (1–
0 bar) using an eightfold parallel autoclave. All starting materials and
1
reactants were used as received from commercial suppliers. Phosphine li-
gands were stored in Schlenk flasks but weighed under air. NMR spectra
were recorded on an ARX300 (Bruker) spectrometer; chemical shifts are
given in ppm and are referenced to TMS or the residual non-deuterated
solvent as internal standard. Mass spectra were recorded on an AMD
4
02 double focusing, magnetic sector spectrometer (AMD Intectra). GC-
MS 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 anilines with hexadecane as internal standard and analysis
by using gas chromatography.
X-ray structure determination: C32
H
39
N
2
P, M
.50ꢃ0.30ꢃ0.13 mm, orthorhombic, space group P2
0.3780(3) ꢄ, b=10.7916(3) ꢄ, c=25.6151(6) ꢄ, V=2868.76(13) ꢄ , Z=
r
=482.62, colorless crystal,
0
1
1 1 1
2 2 ,
a=
3
À3
À1
4, 1calcd =1.117 gcm , m=0.117 mm , T=200 K, 41509 measured, 5645
independent reflections (Rint =0.0439), of which 4297 were observed (I>
2
1 2
s(I)), R =0.0302 (I>2s(I)), wR =0.0595 (all data), 296 refined param-
Full conversion is observed for N-methylindole and iso-
quinoline (Table 3, entries 21 and 23; 70–90% yield), where-
as the reaction of pyridine (Table 3, entries 24 and 25; 28–
eters. Data were collected on a STOE IPDS II diffractometer using
graphite-monochromated MoKa radiation. The structure was solved by
direct methods (SHELXS-97: G. M. Sheldrick, University of Gçttingen,
Germany, 1997) and refined by full-matrix least-squares techniques on F
SHELXL-97: G. M. Sheldrick, University of Gçttingen, Germany, 1997).
XP (Bruker AXS) was used for graphical representation. All fully occu-
pied non-hydrogen atoms were refined anisotropically. One phenyl ring
C10–C15) is disordered nearly equally over two sites. Hydrogen atoms
2
30% yield) gave the desired products in only moderate
(
yields. Notably, in comparison to ligand 11, the pyrrole-
based phosphine 5 gave much better results in the amination
of 4-chloroquinaldine (Table 3, entry 22; >99% yield). 1-
Chloro-2-(phenylethynyl)benzene (Table 3, entry 26), which
was synthesized by a Sonogashira reaction of phenylacety-
lene and 1-bromo-2-chlorobenzene with ligand 10, is suc-
cessfully converted to the corresponding amine in 53%
(
were placed in idealized positions and refined by using a riding model.
CCDC-713326 (11) contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif
[25]
yield.
General procedure for the amination of aryl halides: A 3.0 mL autoclave
In summary, a new robust palladium/phosphine catalyst
system for the selective monoarylation of ammonia with dif-
ferent aryl bromides and chlorides has been developed. The
2
was charged with Pd ACHTUNGTNERNUNG( OAc) (0.9 mg, 2 mol%), ligand 11 (7.7 mg,
8
mol%) or ligand 5 (4.6 mg, 8 mol%), and NaOtBu (38.4 mg, 2 equiv).
If it was a solid, the (hetero)aryl halide was also added at that point. The
filled autoclave was placed into the autoclave device, evacuated, backfil-
led with argon, and then 1,4-dioxane (0.2 mL) was added and the mixture
was stirred at room temperature for 5 min. Then, the corresponding aryl
active catalyst is formed in situ from Pd ACHTUNGTERNNNU(G OAc) and air- and
2
moisture stable phosphines as easy-to-handle pre-catalysts.
The productivity of the catalyst system is comparable to that
halide (if liquid) (0.2 mmol) and a 0.5m NH
3
solution (2.0 mL) in 1,4-di-
[15,16]
of competitive Pd/phosphine systems;
full conversion is
oxane (5 equiv NH ) were added successively under an argon atmos-
3
2
phere. The reaction mixture was pressurized with 10 bar N and heated
achieved with most substrates with 1–2 mol% of Pd source
and a fourfold excess of ligand. One can conclude that the
novel electron-rich and sterically demanding phosphine li-
gands cannot be displaced from the palladium by ammonia
to a significant extent; thus, the deactivation of the catalyst
is prevented by the ligands. Furthermore, a subsequent reac-
tion of the resulting aniline derivatives to the corresponding
diaryl amines was not observed. Although giving a slightly
lower yield of the aniline product, it is demonstrated that
the Pd-catalyzed amination process also works at ambient
pressure. Notably, the optimized system showed an excellent
substrate scope including deactivated, electron-neutral, and
activated halides, o-, m-, and p-substituted substrates, aryl
chlorides, as well as heterocycles. In contrast to the previ-
ously reported Pd-catalyzed procedures, the effective con-
version of halostyrenes, haloindoles, and aminoaryl halides
is possible with this system. The most active ligands are
up to 1208C for 24 h. After the mixture had been cooled to room temper-
ature, it was laced with hexadecane (20 mL) as an internal standard. The
mixture was filtered and the yield was determined by gas chromatogra-
phy.
2
-(Phenylethynyl)aniline (Table 3, entry 21): Following the reaction and
cooling to room temperature, the reaction mixture was purified by
1
column
(
(
chromatography
300 MHz, CDCl ): d=7.48–7.45 (m, 2H), 7.32–7.24 (m, 4H), 7.10–7.04
m, 1H), 6.72–6.65 (m, 2H), 4.60 ppm (brs, 2H); C NMR (75 MHz,
): d=147.0, 132.2, 131.5, 129.8, 128.4, 128.3, 123.3, 118.6, 114.8,
(cyclohexane/ethyl
acetate).
H NMR
3
1
3
CDCl
108.5, 94.9, 85.7 ppm; MS (EI): 193 (100) [M] , 165 (34), 139 (4), 89 (11);
3
+
HRMS: calcd for C14
H
11N: 193.08860; found:193.08853.
Acknowledgements
We thank Dr. W. Baumann, Dr. C. Fischer, A. Koch, S. Buchholz, S.
Schareina, A. Kammer, and S. Rossmeisl for excellent analytical support.
We gratefully acknowledge Evonik (formerly Degussa) for financial sup-
port as well as the precious gift of different chemicals. We also thank Dr.
Kathrin Junge for providing the eightfold parallel autoclave equipment
and technical support.
[26]
either commercially available (ligands 5, 8)
or can be
easily synthesized by the previously reported procedure (li-
[24b]
gands 11, 12).
Chem. Eur. J. 2009, 15, 4528 – 4533
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4531