Recyclable catalysts for palladium-catalyzed aminations of aryl halides

Article abstract of DOI:10.1002/chem.201100984

Aminated and recycled: Palladium/imidazolium phosphane catalysts enable efficient and general aminations of aryl halides, including direct amination with ammonia. Subsequent recycling is possible without any additional heterogenization (see scheme).

Full text of DOI:10.1002/chem.201100984

COMMUNICATION
DOI: 10.1002/chem.201100984
Recyclable Catalysts for Palladium-Catalyzed Aminations of Aryl Halides
Andreas Dumrath, Christa Lꢀbbe, Helfried Neumann, Ralf Jackstell, and
Matthias Beller*[a]
Aromatic amines and their derivatives are of significant
importance in organic chemistry and play an important role
as intermediates for agrochemicals, pharmaceuticals, con-
ducting polymers, and dyes in the chemical industry.[1] In
1985, the first palladium-catalyzed aminations of simple
amines were reported by Yagu-polꢀskii and co-workers.[2]
Later on, Buchwald[3] and Hartwig[4] independently devel-
oped this methodology further. Based on their elegant work
in the last two decades, transition-metal-catalyzed amina-
tions of aryl halides as well as related substrates have
become the most popular tool for their preparation on a
laboratory scale.[5–7]
Whereas easily activated substrates such as aryl iodides
and activated bromides can be coupled with primary and
secondary amines in the presence of a plethora of palladium
and copper catalysts, more challenging substrates including
heterocyclic arenes, aryl mesylates, and chlorides do require
specifically designed ligands for successful coupling process-
Scheme 1. Selected examples of phosphane ligands for Pd-catalyzed ami-
nation (second row: novel cationic imidazolium-based posphane ligands).
es. It is generally accepted that sterically hindered and elec-
tron-rich mono- and bidentate phosphanes represent state-
of-the-art ligands for the latter processes. Typical examples
include the Buchwald-biaryl ligands,[8] Josiphos-type ferroce-
nylphosphanes,[9] aryl-heteroaryl ligands[10,11] and trialkyl-
phosphanes[12] (Scheme 1).
ploying a bulky Josiphos-type phosphane. Recently, Buch-
wald et al. showed the possibility of palladium-catalyzed
aminations in flow with a fully automated microfluidic
system instead of using a batch reaction,[18] whereas Stra-
diotto and co-workers developed a flexible catalyst system
for the cross-coupling of aryl chlorides.[19] Notably, also
copper-catalyzed aminations using ammonia were realized
elegantly by Taillefer and co-workers.[20] Despite of all these
achievements still further advancements are desired to im-
prove the efficiency of the corresponding catalysts. In this
respect, especially the recycling of sophisticated homoge-
nous catalysts in coupling reactions is still challenging.[21,22]
Recently, we demonstrated that cationic imidazolium-based
ligands could be used for this purpose. Indeed, improved
catalytic turnover numbers were achieved for palladium-cat-
alyzed hydroxylations.[23]
Regarding the amine, selective coupling reactions using
ammonia towards primary anilines have only recently been
realized compared with the well-established synthesis of sec-
ondary and tertiary amines.[13] The difficulties in synthesizing
primary amines have been attributed to the formation of
catalytically inactive Pd–ammonia complexes[14] during the
oxidative addition, and the tendency of the complexes to
form stable bridging dimers.[15] Furthermore, the increased
reactivity of the initially resulting anilines might lead to
diaryl amines. Hence, a variety of ammonia equivalents
were employed in the synthesis of anilines. Nevertheless,
direct amination with ammonia is the method of choice due
to its atom efficiency, availability, and low cost.[16]
In 2006, the first selective direct amination of aryl halides
Herein, we report a full account of our work using 2-phos-
phanylmethyl-N,N’-biarylimidazolium ligands in the palladi-
um-catalyzed aminations of aryl halides. The required li-
gands are prepared in a straightforward two-step methyla-
tion–phosphorylation sequence from the corresponding het-
erocycles. Notably, our strategy allows the synthesis of imi-
dazolium salts with different substituents in the 1-, 3-, 4-,
and 5-position. This modular preparation is important for
the fine-tuning of the respective ligands.
with ammonia was published by Hartwig and Shen[17] em-
[a] A. Dumrath, C. Lꢁbbe, Dr. H. Neumann, Dr. R. Jackstell,
Prof. Dr. M. Beller
Leibniz-Institut fꢁr Katalyse e.V. an der Universitꢂt Rostock
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
Fax : (+49)381-1281-5000
E-mail: matthias.beller@catalysis.de
Chem. Eur. J. 2011, 17, 9599 – 9604
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9599

Exploratory experiments using the amination of 1-bromo-
naphthalene as a model system showed that a combination
of PdACHTUNGTRENNUNG(OAc)2 and ligand 2 proved to be the optimal catalyst
system using an ammonia solution in 1,4-dioxane (0.5m) and
NaOtBu as base. To our delight, 97% of 1-aminonaphtha-
lene was obtained under these conditions (Table 1, entry 2).
Comparable results were also achieved in the presence of
Next, we applied the optimized catalyst system PdACHTUNGTRENNUNG(OAc)2/
L2 to the amination of various aryl bromides and chlorides
with ammonia (Table 2). Heterocycles such as 4-chloroqui-
naldine and 5-bromoisoquinoline were aminated in excellent
yield (Table 2, entries 4, 9). Also, sterically hindered as well
as unhindered aryl halides reacted very well (Table 2, en-
[PdACHTUNGTRENNUNG(CH3CN)2Cl2] as a precursor.
Table 2. Palladium-catalyzed amination of aryl halides with ammonia.
Table 1. Pd-catalyzed amination of 1-bromonaphthalene with ammonia:
Variation of different ligands.
Entry
Ligand
R
Yield[b]
[%]
Entry
1
Substrate
Product
Yield[b]
[%]
1
2
3
4
5
1
2
3
4
5
20
97
34
0
98
17
2
3
97[c]
77[d]
6
Ad
27
4
99
7
8
9
10
11
tBu
Cy
Cy
Ph
o-Tolyl
49
58
13
0
5
6
99[c]
99[d]
PR3
PR3
PR3
7
8
98[c]
79[d]
0
12
tBu
7
9
99
13
0
14
15
0
DPPF
15
10
99[c]
[a] Reaction conditions: 1-Bromonaphthalene (0.2 mmol), PdACTHNUTRGNEUNG(OAc)2
(2.0 mol%), L (8.0 mol%), NaOtBu (1.2 equiv), NH3 in 1,4 dioxane
(0.5m, 2.0 mL), N2 (10 bar). [b] Determined twice by gas chromatography
with internal standard hexadecane. DPPF=diphenylphosphanylferro-
cene.
11
12
86[d]
97
13
14
90[c]
50[d]
Interestingly, cyclohexyl-substituted ligands 1 and 5 with-
out methyl substituents in 4- and 5-position of the ligand
backbone revealed much less activity compared with 2,
yielding the product only in 20 and 17% yields, respectively
(Table 1, entries 1 and 5). It should be noted that ligand 1,
which was the best ligand for our recently published catalyt-
ic hydroxylations,[23] offered only low yields in the respective
amination reaction. Using ligand 4, in which the cyclohexyl
groups are exchanged by phenyl substituents, no product at
all was obtained. On the other hand, in the presence of the
cyclohexyl-substituted imidazol-based ligand, 58% of the
desired aniline was obtained demonstrating the advantage
of the imidazolium backbone (Table 1, entry 8).[24] Using
other commercial available ligands such as PCy3 and DPPE
gave no or very low yield in this direct amination (Table 1,
entries 9–15).
15
16
17
99[c]
99[d]
96
18
19
75
62
[a] Reaction conditions: Aryl halide (0.2 mmol), PdACTHNUGTRENUNG(OAc)2 (2.0 mol%),
L2 (8.0 mol%), NaOtBu (2.0 equiv), NH3 (0.5m, 2.0 mL), 1208C, 24 h, N2
(10 bar). [b] Determined twice by gas chromatography with internal stan-
dard hexadecane. [c] Pd
ACHTUNGRTEN(NUNG OAc)2 (1.0 mol%), L2 (4.0 mol%). [d] Pd-
AHCTUNGTRENNUNG
9600
www.chemeurj.org
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9599 – 9604

Recyclable Catalysts for Palladium-Catalyzed Aminations
COMMUNICATION
Table 3. Palladium-catalyzed aminations of aryl halides with different amines.
tries 7, 10, and 1). However,
the highly activated 4-bromo-
benzophenone yielded the cor-
responding primary amine in
moderate yield (62%; Table 2,
entry 19). Notably, the amina-
tion of 1,2-dihaloarenes selec-
tively proceeded to the mono-
aminated products in 99 and
Entry
1
Aryl halide
Amine
Product
Yield[b]
[%]
75%
yield,
respectively
(Table 2, entries 15 and 18). In
the case of bromo-chloroar-
enes, the substitution of the
bromide is fully chemoselec-
tive, which resulted in 96% of
the corresponding 2-chloroani-
line (Table 2, entry 17). It
should be noted, that for all
substrates no diarylated by-
products were found and, in
many cases, the palladium
loading could be decreased to
0.5 mol% giving also excellent
yields (Table 2, entries 3, 6, 8,
11, 14, and 16).
99
2
99
3
4
5
6
99[c]
70[d]
78[e]
0[f]
7
8
95
98
To further demonstrate the
general applicability of our cat-
alyst system, we studied the
9
95[g]
97
palladium-catalyzed
Buch-
10
wald–Hartwig aminations with
primary and secondary amines
(Table 3). Again, we adopted
the optimized reaction condi-
tions from the direct amination
with ammonia to various aryl
bromides and aryl chlorides in
the presence of 13 different
amines. Both cyclic and non-
cyclic aliphatic primary amines
reacted smoothly in the amina-
tion (Table 3, entries 16 and
17). In addition, sterically hin-
dered as well as unhindered
anilines were fully converted
to the corresponding amines
with excellent yields (Table 3,
entries 8 and 11, 10 and 13).
11
98
12
13
14
92
95
93
15
16
89
81
N-aromatic-N-aliphatic
amines are efficiently trans-
formed to tertiary amines
(Table, entry 15) and the acti-
vated 2,3,4-trifluoraniline led
to the desired aminated prod-
uct in 95% yield (Table 3,
entry 7). Also, morpholine and
1-benzylpiperazine were fully
converted showing that hetero-
17
18
99
98[g]
Chem. Eur. J. 2011, 17, 9599 – 9604
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9601

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
www.chemeurj.org
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9599 – 9604

Recyclable Catalysts for Palladium-Catalyzed Aminations
COMMUNICATION
(202 mL, 1.0 mmol), morpholine (105 mL, 1.2 mmol) and 1,4-dioxane
(2.0 mL) was added successively under an argon atmosphere. The
Schlenk tube was closed and heated up to 708C for 16 h. After finishing
the reaction, the mixture was cooled down to room temperature and sub-
sequently mixed with dry hydrogen chloride solution (4n in dried 1,4-di-
oxane). The immediately formed bright yellow precipitate was separated
by filtration and washed carefully with dried 1,4-dioxane, whereas the in-
S. Bꢂhn, L. Neubert, H. Neumann, M. Beller, Angew. Chem. 2010,
122, 8303; Angew. Chem. Int. Ed. 2010, 49, 8126.
[8] Reviews: a) see reference [5k]; b) C. Torborg, M. Beller, Adv.
Synth. Catal. 2009, 351, 3027; c) D. S. Surry, S. L Buchwald, Chem.
Sci. 2011, 2, 27; d) R. Pratap, D. Parrish, P. Gunda, D. Venkatara-
man, M. K. Lakshman, J. Am. Chem. Soc. 2009, 131, 12240.
[9] a) T. Ogata, J. F. Hartwig, J. Am. Chem. Soc. 2008, 130, 13848;
b) see reference [5j]; c) G. D. Vo, J. F. Hartwig, J. Am. Chem. Soc.
2009, 131, 11049; d) J. F. Buergler, A. Togni, Chem. Commun. 2011,
47, 1896; e) A. A. Ibrahim, P.-H. Wei, G. D. Harzmann, N. J. Kerri-
gan, J. Org. Chem. 2010, 75, 7901; f) S. Doherty, J. G. Knight, A. L.
Bell, S. El-Menabawey, C. M. Vogels, A. Decken, S. A. Westcott,
Tetrahedron: Asymmetry 2009, 20, 1437; g) M. C. Willis, Angew.
Chem. 2007, 119, 3470; Angew. Chem. Int. Ed. 2007, 46, 3402.
[10] a) F. Rataboul, A. Zapf, R. Jackstell, S. Harkal, T. Riermeier, A.
Monsees, U. Dingerdissen, M. Beller, Chem. Eur. J. 2004, 10, 2983;
b) A. Zapf, M. Beller, Chem. Commun. 2005, 431; c) M. Beller, A.
Zapf, T. Riermeier, Spec. Chem. 2004, 24, 22; d) S. Harkal, F. Rata-
boul, A. Zapf, C. Fuhrmann, T. Riermeier, A. Monsees, M. Beller,
Adv. Synth. Catal. 2004, 346, 1742; e) N. Schwarz, A. Tillack, K.
Alex, I. A. Sayyed, R. Jackstell, M. Beller, Tetrahedron Lett. 2007,
48, 2897; f) C. Torborg, A. Zapf, M. Beller, ChemSusChem 2008, 1,
91.
tensive red-orange-colored supernatant was just refilled in
a new
Schlenk-tube for the next run. In this tube only 4-chloroquinaldine, mor-
pholine and the base NaOtBu were added. The procedure had been done
three times and all reactions were performed under an argon atmos-
phere.
Acknowledgements
We thank Dr. W. Baumann, Dr. C. Fischer, A. Koch, S. Buchholz, S.
Schareina, A. Kammer, and S. Rossmeisl for the analytical support. We
also thank Dr. Kathrin Junge for providing the eightfold parallel auto-
clave equipment and technical support.
[11] a) C. M. So, Z. Zhou, C. P. Lau, F. Y. Kwong, Angew. Chem. 2008,
120, 6502; Angew. Chem. Int. Ed. 2008, 47, 6402; b) G. Chen, W. H.
Lam, W. S. Fok, H. W. Lee, F. Y. Kwong, Chem. Asian J. 2007, 2,
306; c) G. Chen, A. S. C. Chan, F. Y. Kwong, Tetrahedron Lett. 2007,
48, 473; d) Q. Dai, W. Gao, D. Liu, L. M. Kapes, X. Zhang, J. Org.
Chem. 2006, 71, 3928.
Keywords: amination · anilines · imidazolium ligands ·
palladium · phosphane ligands
[1] a) M. S. Driver, J. F. Hartwig, J. Am. Chem. Soc. 1996, 118, 7217–
7218; b) K. Weissermel, H. J. Arpe, Industrial Organic Chemistry,
Wiley-VCH, Weinheim, 1997; c) S. A. Lawrence, Amines: Synthesis
Properties, and Application, Cambridge University Press, Cam-
bridge, 2004.
[2] N. V. Kondratenko, A. A. Kolomeitsev, V. O. Mogilevskaya, N. M.
Varlamova, L. M. Yagu-polꢀskii, Zh. Org. Khim. (Russ.) 1986, 22,
1721.
[12] For applications of di(adamantyl)-1-butylphosphane, see: a) A.
Zapf, A. Ehrentraut, M. Beller, Angew. Chem. 2000, 112, 4315;
Angew. Chem. Int. Ed. 2000, 39, 4153; b) S. Klaus, H. Neumann, A.
Zapf, D. Strꢁbing, S. Hꢁbner, J. Almena, T. Riermeier, P. Groß, M.
Sarich, W.-R. Krahnert, K. Rossen, M. Beller, Angew. Chem. 2006,
118, 161; Angew. Chem. Int. Ed. 2006, 45, 154; c) A. Ehrentraut, A.
Zapf, M. Beller, J. Mol. Catal. 2002, 182–183, 515; d) A. Ehrentraut,
A. Zapf, M. Beller, Adv. Synth. Catal. 2002, 344, 209; e) A. Tewari,
M. Hein, A. Zapf, M. Beller, Synthesis 2004, 935; f) H. Neumann,
A. Brennfꢁhrer, P. Groß, T. Riermeier, J. Almena, M. Beller, Adv.
Synth. Catal. 2006, 348, 1255; g) A. Brennfꢁhrer, H. Neumann, S.
Klaus, P. Groß, T. Riermeier, J. Almena, M. Beller, Tetrahedron
2007, 63, 6252; h) A. Brennfꢁhrer, H. Neumann, M. Beller, Synlett
2007, 2537; i) T. Schareina, A. Zapf, W. Mꢂgerlein, N. Mꢁller, M.
Beller, Tetrahedron Lett. 2007, 48, 1087; j) H. Neumann, A. Brenn-
fꢁhrer, M. Beller, Chem. Eur. J. 2008, 14, 3645; k) H. Neumann, A.
Brennfꢁhrer, M. Beller, Adv. Synth. Catal. 2008, 350, 2437; l) H.
Neumann, A. Sergeev, M. Beller, Angew. Chem. 2008, 120, 4965;
Angew. Chem. Int. Ed. 2008, 47, 4887; m) J. A. Smith, R. K. Jones,
G. W. Booker, S. M. Pyke, J. Org. Chem. 2008, 73, 8880. For applica-
tions of tri-(tert)butylphosphane see: n) S. G. Newman, M. Lautens,
J. Am. Chem. Soc. 2010, 132, 11416; o) M. Prashad, X. Y. Mak, Y.
Liu, J. Org. Chem. 2003, 68, 1163; p) R. Kuwano, M. Utsunomiya,
J. F. Hartwig, J. Org. Chem. 2002, 67, 6479; q) K. Weigand, S. Pelka,
Org. Lett. 2002, 4, 4689; r) J. F. Hartwig, M. Kawatsura, S. I. Hauck,
K. H. Shaughnessy, L. M. Alcazar-Roman, J. Org. Chem. 1999, 64,
5575.
[3] A. S. Guram, R. A. Rennels, S. L. Buchwald, Angew. Chem. 1995,
107, 1456; Angew. Chem. Int. Ed. Engl. 1995, 34, 1348.
[4] a) F. Paul, J. Patt, J. F. Hartwig, J. Am. Chem. Soc. 1994, 116, 5969;
b) J. Louie, J. F. Hartwig, Tetrahedron Lett. 1995, 36, 3609.
[5] Reviews: a) L. Jiang, S. L. Buchwald in Metal Catalyzed Cross-Cou-
pling Reactions, 2nd ed. (Eds.: A. de Meijere, F. Diederich), Wiley-
VCH, Weinheim, 2004; b) J. F. Hartwig, Synlett 2006, 1283; c) J. F.
Hartwig in Modern Arene Chemistry: Concepts, Synthesis, and Ap-
plications (Ed.: C. Austruc), Wiley-VCH, Weinheim, 2002, p. 107;
d) A. R. Muci, S. L. Buchwald, Top. Curr. Chem. 2002, 219, 131;
e) J. F. Hartwig in Handbook of Organopalladium Chemistry for Or-
ganic Synthesis, Vol. 1 (Eds.: E. Negishi, A. de Meijere), Wiley, New
York, 2002, p. 1051; for reviews on Pd-catalyzed coupling reactions
including aminations see: f) S. L. Buchwald, C. Mauger, G. Mignani,
U. Scholz, Adv. Synth. Catal. 2006, 348, 23; g) E. A. B. Kantchev,
C. J. OꢀBrien, M. G. Organ, Angew. Chem. 2007, 119, 2824; Angew.
Chem. Int. Ed. 2007, 46, 2768; h) S. Tasler, J. Mies, M. Langa, Adv.
Synth. Catal. 2007, 349, 2286; i) N. Marion, S. P. Nolan, Acc. Chem.
Res. 2008, 41, 1440; j) J. F. Hartwig, Acc. Chem. Res. 2008, 41, 1534;
k) D. S. Surry, S. L. Buchwald, Angew. Chem. 2008, 120, 6438;
Angew. Chem. Int. Ed. 2008, 47, 6338.
[13] a) See reference [4a]; b) A. S. Guram, S. L. Buchwald, J. Am. Chem.
Soc. 1994, 116, 7901; c) J. P. Wolfe, S. L. Buchwald, Org. Synth. 2002,
78, 23; d) M. Mataloni, M. Petrini, R. Profeta, Synlett 2003, 1129;
e) M. W. Carlson, J. T. Ciszewski, M. M. Bhatti, W. F. Swanson,
A. M. Wilson, J. Chem. Educ. 2000, 77, 270.
[14] a) R. A. Widenhoefer, S. L. Buchwald, Organometallics 1996, 15,
2755; b) R. A. Widenhoefer, S. L. Buchwald, Organometallics 1996,
15, 3534; c) F. Paul, J. Patt, J. F. Hartwig, Organometallics 1995, 14,
3030.
[6] Recent examples of Pd-catalyzed aminations: a) Y. Tan, J. F. Hart-
wig, J. Am. Chem. Soc. 2010, 132, 3676; b) B. P. Fors, S. L. Buchwald,
J. Am. Chem. Soc. 2010, 132, 15914; c) J. L. Henderson, S. M.
McDermott, S. L. Buchwald, Org. Lett. 2010, 12, 4438; d) S. Rodri-
guez, B. Qu, N. Haddad, D. C. Reeves, W. Tang, H. Lee, D. Krishna-
murthy, C. H. Senanayake, Adv. Synth. Catal. 2011, 353, 533; e) C.
Ronco, L. Jean, H. Outaabout, P.-Y. Renard, Eur. J. Org. Chem.
2011, 302.
[7] For other recent catalytic syntheses of N-substituted anilines, see:
a) D. Hollmann, S. Bꢂhn, A. Tillack, M. Beller, Angew. Chem. 2007,
119, 8440; Angew. Chem. Int. Ed. 2007, 46, 8291; b) D. Hollmann, S.
Bꢂhn, A. Tillack, M. Beller, Chem. Commun. 2008, 3199; c) S. Imm,
[15] a) S. Park, A. L. Rheingold, D. M. Roundhill, Organometallics 1991,
10, 615; b) A. L. Casalnuovo, J. C. Calabrese, D. Milstein, Inorg.
Chem. 1987, 26, 971.
Chem. Eur. J. 2011, 17, 9599 – 9604
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9603

M. Beller et al.
[16] For the application of ammonia as a reagent in other catalytic ami-
nation processes, see: a) T. Gross, A. M. Seayad, M. Ahmad, M.
Beller, Org. Lett. 2002, 4, 2055; b) D. M. Roundhill, Chem. Rev.
1992, 92, 1; c) B. Zimmermann, J. Herwig, M. Beller, Angew. Chem.
Int. Ed. 1999, 38, 2372; d) T. Prinz, B. Driessen-Holscher, Chem.
Eur. J. 1999, 5, 2069; e) T. Prinz, W. Keim, B. Driessen-Holscher,
Angew. Chem. 1996, 108, 1835; Angew. Chem. Int. Ed. Engl. 1996,
35, 1708; f) S. Ogo, K. Uehara, T. Abura, S. Fukuzumi, J. Am.
Chem. Soc. 2004, 126, 3020; g) A. Martin, M. Kant, R. Jackstell, H.
Klein, M. Beller, Chem. Ing. Tech. 2007, 79, 891; h) H. Klein, R.
Jackstell, M. Kant, A. Martin, M. Beller, Chem. Eng. Technol. 2007,
30, 721.
[17] Q. Shen, J. F. Hartwig, J. Am. Chem. Soc. 2006, 128, 10028.
[18] T. Noꢄl, J. R. Naber, R. L. Hartman, J. P. McMullen, K. F. Jensen,
S. L. Buchwald, Chem. Sci. 2011, 2, 287.
[19] R. J. Lundgren, A. Sappong-Kumankumah, M. Stradiotto, Chem.
Eur. J. 2010, 16, 1983.
[20] a) N. Xia, M. Taillefer, Angew. Chem. 2009, 121, 343; Angew. Chem.
Int. Ed. 2009, 48, 337; b) M. Taillefer, N. Xia, Fr 06827, 2007; c) F.
Lang, D. Zewge, I. N. Houpis, R. P. Volante, Tetrahedron Lett. 2001,
42, 3251; d) J. Kim, S. Chang, Chem. Commun. 2008, 3052; e) F.
Meng, X. Zhu, Y. Li, J. Xie, B. Wang, J. Yao, Y. Wan, Eur. J. Org.
Chem. 2010, 6149; f) C. A. Anderson, P. G. Taylor, M. A. Zeller,
S. C. Zimmerman, J. Org. Chem. 2010, 75, 4848; g) D. Wang, Q. Cai,
K. Ding, Adv. Synth. Catal. 2009, 351, 1722; h) X. Diao, Y. Wang, Y.
Jiang, D. Ma, J. Org. Chem. 2009, 74, 7974.
9870; c) C. A. Parrish, S. L. Buchwald, J. Org. Chem. 2001, 66, 3820;
d) T. Welton, Chem. Rev. 1999, 99, 2071; e) R. Sheldon, Chem.
Commun. 2001, 2399; f) P. Wasserscheid, W. Keim, Angew. Chem.
2000, 112, 3926; Angew. Chem. Int. Ed. 2000, 39, 3772; g) H. Olivier-
Bourbigou, L. Magna, J. Mol. Catal. A: Chem. 2002, 182–183, 419;
h) Ionic Liquids in Synthesis (Eds.: P. Wasserscheid, T. Welton),
Wiley-VCH, Weinheim, 2002, i) P. Wasserscheid, Chem. Unserer Zeit
2003, 37, 52.
[22] a) S. S. Prçckl, W. Kleist, K. Kçhler, Tetrahedron 2005, 61, 9855;
b) K. Kçhler, R. G. Heidenreich, S. S. Soomro, S. Prçckl, Adv.
Synth. Catal. 2008, 350, 2930; c) W. Kleist, J.-K. Lee, K. Kçhler, Eur.
J. Inorg. Chem. 2009, 261; d) M. Lamblin, L. Nassar-Hardy, J.-C.
Hierso, E. Fouquet, F.-X. Felpin, Adv. Synth. Catal. 2010, 352, 33;
e) Y. Monguchi, Y. Fujita, K. Endo, S. Takao, M. Yoshimura, Y.
Takagi, T. Maegawa, H. Sajiki, Chem. Eur. J. 2009, 15, 834; f) M.-J.
Jin, D.-H. Lee, Angew. Chem. 2010, 122, 1137; Angew. Chem. Int.
Ed. 2010, 49, 1119; g) S. Wittmann, A. Schꢂtz, R. N. Grass, W. J.
Stark, O. Reiser, Angew. Chem. 2010, 122, 1911; Angew. Chem. Int.
Ed. 2010, 49, 1867.
[23] A. Dumrath, X.-F. Wu, H. Neumann, A. Spannenberg, R. Jackstell,
M. Beller, Angew. Chem. 2010, 122, 9172; Angew. Chem. Int. Ed.
2010, 49, 8988.
[24] T. Schulz, C. Torborg, S. Enthaler, B. Schꢂffner, A. Dumrath, A.
Spannenberg, H. Neumann, A. Bçrner, M. Beller, Chem. Eur. J.
2009, 15, 4528.
[21] For selected examples, see a) M. Guinꢅ, K. K. M. Hii, Chem. Soc.
Rev. 2007, 36, 608; b) Y.-C. Yang, T.-Y. Luh, J. Org. Chem. 2003, 68,
Received: March 31, 2011
Published online: July 29, 2011
9604
www.chemeurj.org
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9599 – 9604