New ligands for a general palladium-catalyzed amination of aryl and heteroaryl chlorides

Article abstract of DOI:10.1002/chem.200306026

The synthesis and application of monodentate N-substituted heteroarylphosphines is described. In general, the ligands are conveniently prepared by selective metallation at the 2-position of the respective N-substituted heterocycle (pyrrole, indole) by using n-butyllithium/ tetramethylethylenediamine (TMEDA) followed by quenching with dialkyl- or diarylchlorophosphines. Of the different ligands prepared, the new dialkyl-2-(N-arylindolyl)phosphines (cataCXium P) perform excellently in the palladium-catalyzed amination of aryl and heteroaryl chlorides. Coupling of both activated and deactivated chloroarenes proceeds under mild conditions (room temperature to 60°C). By using optimized conditions remarkable catalyst productivity (total turnover number, TON, up to 8000) and activity (turnover frequency, TOF = 14000 h^-1 at 75% conversion) are observed.

Full text of DOI:10.1002/chem.200306026

FULL PAPER
New Ligands for a General Palladium-Catalyzed Amination of Aryl and
Heteroaryl Chlorides
Franck Rataboul,[a] Alexander Zapf,[a] Ralf Jackstell,[a] Surendra Harkal,[a]
Thomas Riermeier,[b] Axel Monsees,[b] Uwe Dingerdissen,[b] and Matthias Beller*[a]
Abstract: The synthesis and application
of monodentate N-substituted hetero-
arylphosphines is described. In general,
the ligands are conveniently prepared
by selective metallation at the 2-posi-
tion of the respective N-substituted
heterocycle (pyrrole, indole) by using
n-butyllithium/tetramethylethylenedi-
amine (TMEDA) followed by quench-
ing with dialkyl- or diarylchlorophos-
phines. Of the different ligands pre-
aryl chlorides. Coupling of both acti-
vated and deactivated chloroarenes
proceeds under mild conditions (room
temperature to 608C). By using opti-
mized conditions remarkable catalyst
productivity (total turnover number,
TON, up to 8000) and activity (turn-
over frequency, TOF=14000 hÀ1 at
75% conversion) are observed.
pared, the new dialkyl-2-(N-arylindo-
¾
lyl)phosphines (cataCXium P) per-
form excellently in the palladium-
catalyzed amination of aryl and hetero-
Keywords: amination
¥ anilines ¥
aryl chlorides ¥ catalysis ¥ palladium ¥
phosphines
Introduction
tools in the laboratory scale synthesis of aryl amines.[2] Of
the different substrates that are available, economically at-
tractive aryl chlorides require special catalyst design for suc-
cessful coupling, unlike aryl iodides or bromides. This is
either a consequence of the thermodynamics (experimental
bond dissociation energies have been found to be 402, 339,
and 272 kJmolÀ1 at 298 K for chloro-, bromo-, and iodoben-
zene, respectively)[3] or kinetics, depending on the reaction
conditions.[4] With regard to catalyst development, tri-o-tol-
ylphosphine[5] was originally used as the ligand, but this
phosphine gave poor results with primary amines and did
not work with nonactivated aryl chlorides. Next, chelating
bis-phosphine ligands like 2,2’-bis(diphenylphosphino)-1,1’-
binaphthyl (BINAP)[6] and 1,1’-bis(diphenylphosphino)ferro-
cene (DPPF) or 1,1’-bis(di-tert-butylphosphino)ferrocene
(DtBPF)[7] (1 3) were introduced as a second generation of
Aromatic amines (anilines) are of fundamental interest in
the fine chemical industry owing to their importance as
building blocks for pharmaceuticals, agrochemicals, and new
materials. Since the mid 1990s an elegant approach has been
developed for the synthesis of these compounds based on
the direct coupling of aryl halides and amines. This so-called
™Buchwald Hartwig amination∫ reaction occurs in the pres-
ence of palladium catalysts with various phosphine ligands
and an excess of base (Scheme 1).[1]
À
Clearly, this relatively new methodology for C N bond
formation has already become one of the most important
Scheme 1. Pd-catalyzed amination of aryl halides.
[a] Dr. F. Rataboul, Dr. A. Zapf, Dr. R. Jackstell, S. Harkal,
Prof. Dr. M. Beller
Leibniz-Institut f¸r Organische Katalyse
an der Universit‰t Rostock e.V.
Buchbinderstrasse 5 6
18055 Rostock (Germany)
Fax : (+49)381-466-9324
E-mail: matthias.beller@ifok.uni-rostock.de
catalysts, and have been shown to be efficient with primary
amines under mild conditions.
Nevertheless, these ligands did not give satisfactory results
when aryl chlorides were used as substrates. Later, the use
[b] Dr. T. Riermeier, Dr. A. Monsees, Dr. U. Dingerdissen
Degussa AG, Creavis Technologies & Innovation
Project House Catalysis, Industriepark Hˆchst, G830
65926 Frankfurt am Main (Germany)
Chem. Eur. J. 2004, 10, 2983 2990
DOI: 10.1002/chem.200306026
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2983

FULL PAPER
of tri-tert-butylphosphine in a general amination protocol of
aryl chlorides was reported by Koie and co-workers.[8] Un-
fortunately, this commercially available ligand is highly sen-
sitive to air, which limits its applications. Wolfe and Buch-
wald synthesized sterically demanding basic phosphines,
such as o-(dicyclohexylphosphino)biphenyl (4) or o-(di-tert-
butylphosphino)biphenyl ligands (5), which are more stable
gands to the palladium-catalyzed amination of aryl and het-
eroaryl chlorides
Results and Discussion
Based on the work of Faigl and co-workers, who have
shown that N-arylpyrroles can be deprotonated selectively
at the a-position to the nitrogen atom,[16] we have synthe-
sized different 2-phosphino-N-arylpyrroles (7 13). Typically
the corresponding N-arylpyrrole was deprotonated by using
a mixture of nBuLi (1.0 equiv) and TMEDA (1.5 equiv) in
hexane. For selective deprotonation ortho to the nitrogen
atom the use of an excess of TMEDA proved to be crucial.
After refluxing the reaction mixture, the intermediate carb-
anion was trapped with a solution of the respective chloro-
phosphine. In all cases the phosphines were obtained after
crystallization with purities >95%. Clearly this efficient
protocol should be applicable to other N-arylpyrroles that
are commercially available or that are easily synthesized
from anilines[17] or by palladium-[18] or copper-catalyzed[19]
arylation of pyrrole. In addition, we thought that other het-
erocycles, for example, indoles, could also be used as sub-
strates. Thus, we prepared N-phenylindole by copper-cata-
lyzed arylation of indole with bromobenzene in 85%
yield.[19a] Subsequent deprotonation with nBuLi/TMEDA
and reaction with chlorodicyclohexylphosphine, chlorodi-1-
adamantylphosphine and chlorodi-tert-butylphosphine gave
the ligands 14 16, without much optimization, in yields of
45 to 60% (Scheme 2).
in air and allow room temperature aminations of aryl chlor-
ides.[9] More recently, our group reported di-1-adamantyl(n-
butyl)phosphine (6)[10] to be a very active ligand for the cou-
pling of a wide range of sterically congested aryl chlorides
with hindered amines.[11] This now commercially available
¾
ligand (cataCXium A) is more stable than the P(tBu)3
system. In addition, it should be noted that N-heterocyclic
carbenes have also been used successfully for the amination
of aryl chlorides.[12] However the use of carbene ligands gen-
erally results in lower catalyst productivity than is the case
with phosphine ligands.[13]
We have a long-standing interest in the practical applica-
tion of palladium-catalyzed coupling reactions.[14] In this re-
spect the stability, productivity, modular variation and ease
of preparation of the known catalysts for Buchwald Hartwig
aminations of chloroarenes can still be improved. Very re-
cently, we reported the synthesis of a new class of mono-
phosphine ligands based on the 2-phosphino-N-arylpyrrole
structure (7 13) by selective ortho-metallation of the corre-
sponding pyrrole and subsequent reaction with R2PCl.[15]
Initially, ligands 7 16 were tested in the coupling of
chlorobenzene with aniline, which is one of the more diffi-
cult aminations to perform, by using previously optimized
[11]
reaction conditions (Table 1).
As shown in Table 1, when simple phenyl- or cyclohexyl-
substituted pyrrole or indole derivatives were used, poor re-
sults were obtained (ligands 7, 8, and 14; Table 1, entries 1,
2, and 8). Apparently the steric demand of the ligands is not
sufficient to allow the formation of active catalysts. Howev-
er, when the N-phenyl ring was substituted the catalytic ac-
tivity increased to give yields of up to 68% (ligands 11 and
Most of these ligands led to extremely efficient catalysts for
the Suzuki cross-coupling of aryl chlorides.[15] Here, we de-
scribe for the first time a full
account of our synthesis of 2-
phosphino-N-arylpyrroles. Fur-
thermore, the synthesis of new
2-phosphino-N-arylindole
li-
gands (14 16) is presented as
well as the application of the
pyrrole- and indole-based li- Scheme 2. Synthesis of N-phenylindole-based phosphine ligands.
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¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2004, 10, 2983 2990

Palladium-Catalyzed Amination
2983 2990
Table 1. Amination[a] of chlorobenzene with aniline using ligands 7 16.
12; Table 1, entries 5 and 6). When tert-butylphosphino de-
rivatives were used, better conversions and yields were ob-
tained (up to 95% yield) due to the increase in the steric
demand of the ligands (ligands 9, 13, and 15; Table 1, en-
tries 3, 7, and 9). We have demonstrated that these new li-
gands work at least as well as ™state-of-the-art∫ ligands, such
as P(tBu)3 and di-1-adamantyl(n-butyl)phosphine (cataCXi-
Entry
1
Ligand
Conv.
[%][b]
Yield
[%][b]
TON
2
¾
um A), in the chloroarene amination test reactions
(Table 1, entries 11 and 12).
2
11
1
9
The general usefulness of the new ligands is shown in
Tables 2 and 3. The reactions of 15 aryl and heteroaryl
chlorides with different amines were performed. In most
cases the corresponding anilines were obtained in good to
excellent yield (>90%) at low catalyst concentration
(0.5 mol% Pd). Chlorobenzene can be coupled efficiently
with aliphatic amines (Table 2, entries 2 and 3). Primary and
2
3
4
5
6
7
18
190
152
124
136
174
100
77
95
76
62
68
87
[a]
Table 2. Palladium-catalyzed aminations of chlorobenzene using ligand
15.
Entry
Amine
Product
Conv.
[%][b]
Yield
[%][b]
1[c]
100
100
100
95
97
91
2
62
3
69
4
100
100
100
94
99
95
91
5[d]
6
8
13
100
49
9
95
46
18
190
92
[a] 5 mmol chlorobenzene, 6 mmol amine, 6 mmol NaOtBu, 0.5 mol%
Pd(OAc)2, 1 mol% ligand 15, 5 mL toluene, 20 h, 1208C. The reaction
time has not been minimized. [b] Average of 2 runs, determined by GC
using diethylene glycol di-n-butyl ether or hexadecane as internal stan-
dard. [c] 48 h. [d] Ligand 12 was used.
9
secondary aromatic amines proved to be efficient coupling
partners, too (Table 2, entries 1, 4 6). In the case of the hin-
dered diphenylamine a better result was obtained by using
the sterically less demanding ligand 12 instead of 15.
10
The amination of functionalized aryl and heteroaryl hal-
ides with aliphatic and aromatic amines shows the usefulness
of our catalytic system (Table 3). For example, excellent re-
sults (88 99% yield) were obtained with different chloro-
toluenes and chloroxylenes (Table 3, entries 1 7). Cyano-,
methoxy-, and fluoro-substituted aryl chlorides also gave
high yields (75 98%) of the corresponding anilines (Table 3,
entries 8 13). Heterocycles like 2- or 3-chloropyridine can
also be aminated successfully (90 99% yield; Table 3, en-
11
12
96
99
85
92
170
184
P(tBu)3
[a] 5 mmol aryl chloride, 6 mmol amine, 6 mmol NaOtBu, 0.5 mol%
Pd(OAc)2, 1 mol% ligand, 5 mL toluene, 48 h, 1208C. [b] Average of
2 runs, determined by GC using diethylene glycol di-n-butyl ether as in-
ternal standard.
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M. Beller et al.
FULL PAPER
Table 3. Amination[a] of functionalized aryl and heteroaryl chlorides using ligand 14 or 15.
Entry
1
Aryl chloride
Amine
Product
Conv. [%][b]
100
Yield [%][b]
99
88
95
95
2
3
4
100
100
100
5
100
100
100
100
92
95
91
75
6
7
8[c]
9
100
100
88
90
10
11
12
13
100
100
100
97
98
98
14
100
100
100
60 (15) 99 (14)
92
15[c]
16
77 (15) 99 (14)
tries 14 19). In some cases the sterically less demanding
ligand 14 gave superior results than ligand 15.
Owing to the excellent results obtained, we investigated
the amination of aryl chlorides under milder reaction condi-
tions and at lower catalyst concentrations. As a model
system for a nonactivated aryl chloride, 3-chlorotoluene was
treated with N-methylaniline in the presence of Pd(OAc)2
and 2-(di-tert-butylphosphino)-N-phenylindole (15) as the
catalyst system (Table 4).
Under standard conditions (0.5 mol% Pd, 1 mol% ligand,
1208C), a yield of 95% was obtained (Table 4, entry 1). We
were surprised to find that by decreasing the temperature to
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Chem. Eur. J. 2004, 10, 2983 2990

Palladium-Catalyzed Amination
2983 2990
Table 3. (Continued)
Entry
Aryl chloride
Amine
Product
Conv. [%][b]
100
Yield [%][b]
17
99 (14)
18
100
100
90
99
19[c]
[a] 5 mmol aryl chloride, 6 mmol amine, 6 mmol NaOtBu, 0.5 mol% Pd(OAc)2, 1 mol% ligand, 5 mL toluene, 20 h, 1208C. The reaction time has not
been minimized. [b] Average of 2 runs, determined by GC using diethylene glycol di-n-butyl ether or hexadecane as internal standard. [c] 1 mol%
Pd(OAc)2, 2 mol% ligand.
Table 4. Reaction conditions for the reaction of 3-chlorotoluene with N-
Finally, the amination of different aryl chlorides at low
temperatures was studied in more detail. Table 5 demon-
methylaniline.[a]
strates that excellent results can be obtained at room tem-
perature with activated aryl chlorides by using 1 mol% cata-
lyst (Table 5, entries 1 and 2). For nonactivated and deacti-
vated aryl chlorides, high yields (>90%) of the correspond-
ing anilines were obtained at a temperature of 608C. Owing
to the mild conditions the new catalyst system seems to be
useful for more sensitive substrates, too (e.g., Table 5,
entry 7).
Entry
Pd
[mol%]
L/Pd
T
[8C]
Conv.
[%][b]
Yield
[%][b]
TON
1
2
3
4
5
6
7
8
9
0.5
0.5
0.5
0.25
0.1
0.05
0.025
0.025
0.025
0.01
0.01
0.01
2
2
2
2
2
120
80
40
100
100
100
100
98
83
70
78
92
95
90
90
91
86
73
62
67
80
23
37
80
190
180
180
364
860
1460
2480
2680
3200
2300
3700
8000
120
120
120
120
120
140
120
120
140
2
2
Conclusions
10
10
2
50
50
Monodentate N-substituted heteroarylphosphines have been
conveniently synthesized by selective metallation at the 2-
position of the respective N-substituted heterocycle (pyrrole,
indole). The variety of available ligands (7 16) reflects
nicely the modular synthesis. This is very important, since
the synthesis of more complex molecules by palladium-cata-
lyzed coupling reactions often requires fine-tuning of the
catalytic system. In general, other known ligands require
more complex chemistry to achieve diversity.
10
11
12
24
45
100
[a] 5 mmol 3-chlorotoluene, 6 mmol N-methylaniline, 6 mmol NaOtBu,
Pd(OAc)2, ligand 15, 5 mL toluene, 20 h. The reaction time has not been
minimized. [b] Average of 2 runs, determined by GC using diethylene
glycol di-n-butyl ether as internal standard.
408C, only a slight decrease in the activity was observed
(Table 4, entries 2 and 3). At a higher temperature the con-
version decreased in parallel with the decrease in catalyst
loading. The conversion decreased significantly by lowering
the catalyst concentration to 0.01 mol% Pd (23% yield;
turnover number (TON) 2300; Table 4, entry 10). However,
by increasing the ligand concentration to 0.5 mol% (L/Pd
50:1) and by raising the temperature to 1408C a good cou-
pling yield of 80% (TON=8000) was obtained. In addition
to catalyst productivity studies, we also investigated the ac-
tivity of the catalyst. While most of the reactions were
simply performed for a standard reaction time (e.g., 20 h),
catalyst activity was measured by using the conditions de-
scribed in Table 4, entry 12. We found that this catalyst
system has a comparably high activity. Even after 30 min ap-
proximately 75% conversion and 70% product yield were
obtained; this corresponds to a turnover frequency (TOF)
of 14000 hÀ1. Naturally, even higher turnover frequencies
can be expected at lower conversion.
For the first time palladium-catalyzed aminations of aryl
halides have been performed in the presence of N-substitut-
ed heteroarylphosphines. In general, excellent results have
been obtained for the coupling of a variety of aryl and het-
eroaryl chlorides in the presence of dialkylphosphino-N-ary-
lindoles 14 and 15. Remarkably, high yields (>90%) were
obtained under mild conditions (RTto 60 8C). On the other
hand excellent catalyst productivity (TON 8000) and activity
(TOF=14000 hÀ1 at 75% conversion) were observed for
the model reaction of 3-chlorotoluene and N-methylaniline
at a higher reaction temperature. Owing to their excellent
catalytic performance and convenient preparation this class
of ligands will be commercially available from 2004 under
¾
the trade name cataCXium P.
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M. Beller et al.
FULL PAPER
Table 5. Amination[a] of aryl chlorides at low temperatures.
TMEDA (3.35 mL, 22.5 mmol) was
added followed by nBuLi (1.6m in
hexane, 7.2 mL, 15 mmol) at room
temperature. The reaction mixture was
refluxed for 3 h to obtain a red solu-
tion. A solution of the corresponding
chlorophosphine (15 mmol in 15 mL of
toluene) was slowly added through a
syringe. The mixture was refluxed for
a further 2 h. After cooling to room
temperature, degassed water (15 mL)
was added and the mixture was stirred
to give a clear solution. The aqueous
layer was extracted with toluene (2î
15 mL), and the combined organic
layers were washed with degassed
water (15 mL). The solution was dried
over MgSO4 and concentrated at 458C
under vacuum to give a yellow viscous
liquid which was recrystallized from
methanol or hexane.
Entry
Aryl chloride
Amine
Product
T
[8C]
Yield
[%][b]
1[c]
25
25
97
98
2[c]
3
4
60
60
91
98
2-(Dicyclohexylphosphino)-N-phenyl-
indole (14): White solid (cryst from
hexane); yield 60%; m.p. 157 1598C;
1H NMR (400 MHz, C6D6): d=7.69
(m, 1H), 7.53 7.42 (m, 3H), 7.32 (m,
2H), 7.14 (m, 3H), 6.85 (s, 1H), 1.72
1.65 (m, 11H), 1.27 1.02 ppm (m,
11H); 13C NMR (101 MHz, C6D6): d=
140.3, 138.9, 137.4, 137.3, 129.9 (d,
2J(C,P)=2.9 Hz), 129.0, 128.2, 128.0,
122.3, 120.3, 111.0, 110.2 (d, 1J(C,P)=
3.8 Hz), 30.3 (d, 1J(C,P)=15.3 Hz),
27.4 (d, 2J(C,P)=12.4 Hz), 27.2 (d,
3J(C,P)=8.6 Hz), 26.6 ppm; 31P NMR
(162 MHz, C6D6): d=À24.8 ppm; IR
(KBr): n˜ =3059.3, 2924.1, 2847.0,
2637.2, 1596.8, 1496.3, 1307.6, 1145.0,
737.2, 695.9 cmÀ1; MS (70 eV, EI): m/z
5
6
60
60
97
91
7[d]
65
64
[a] 5 mmol aryl chloride, 6 mmol amine, 6 mmol NaOtBu, 0.5 mol% Pd(OAc)2, 1 mol% ligand 15, 5 mL tolu-
ene, 20 h. The reaction time has not been minimized. [b] Average of 2 runs, determined by GC using diethy-
lene glycol di-n-butyl ether or hexadecane as internal standard. [c] 1 mol% Pd(OAc)2, 2 mol% ligand 15.
[d] 1 mmol aryl chloride, 1.2 mmol amine, 1.2 mmol NaOtBu.
(%): 389 (48) [M+], 306 (90), 224 (100), 193 (17), 83 (8), 55 (25), 41 (19);
Experimental Section
HRMS: calcd for C26H32NP: 389.22723; found: 389.22922.
General: Ligands were synthesized and stored under an inert atmosphere
using Schlenk techniques. All starting materials and reactants were used
as received from commercial suppliers, except TMEDA which was distil-
led and degassed before use. NMR spectra were recorded on an
ARX400 (Bruker) spectrometer; chemical shifts are given in ppm and
are referenced to TMS (1H, 13C NMR), H3PO4 (80% in water; 31P NMR)
and CFCl3 (19F NMR). IR spectra were recorded on a Magna-IR-
series 550 (Nicolet) spectrometer. Mass spectra were recorded on an
AMD 402 double focusing, magnetic sector spectrometer (AMD Intec-
tra). GC-MS spectra were recorded on a HP 5989A (Hewlett Packard)
chromatograph equipped with a quadrupole analyzer. Gas chromato-
graphic analyses were realized on a HP 6890 (Hewlett Packard) chroma-
tograph using a HP 5 column.
2-(Di-tert-butylphosphino)-N-phenylindole (15): Pale yellow solid (cryst
from MeOH); yield 50%; m.p. 90 928C; H NMR (400 MHz, C6D6): d=
1
8.01 (m, 1H), 7.82 7.74 (m, 3H), 7.58 (m, 2H), 7.45 (m, 2H), 7.41 (s,
1H), 7.32 (m, 1H), 1.50 ppm (d, 3J(H,P)=12.3 Hz, 18H); 13C NMR
(101 MHz, C6D6): d=140.1, 139.6, 138.1, 137.9, 130.5 (d, 2J(C,P)=
1
2.9 Hz), 129.2, 128.4, 128.1, 122.7, 120.8, 120.5, 116.6 (d, J(C,P)=5.7 Hz),
33.2 (d, 1J(C,P)=18.1 Hz), 30.6 ppm (d, 2J(C,P)=15.3 Hz); 31P NMR
(162 MHz, C6D6): d=5.85 ppm; IR (KBr): n˜ =3058.7, 2937.1, 2892.3,
2857.8, 1595.9, 1496.8, 1469.2, 1361.9, 763.1, 742.4, 700.0 cmÀ1; MS (EI,
70 eV): m/z (%): 337 (42) [M+], 281 (30), 224 (100), 193 (19), 57 (30), 41
(20); HRMS: calcd for C22H28NP: 337.19595; found: 337.19584.
2-(Di-1-adamantylphosphino)-N-phenylindole (16): White solid (cryst
1
from hexane); yield 45%; m.p. 308 3108C; H NMR (400 MHz, CD2Cl2):
Synthesis of N-phenylindole: Dioxane (50 mL), followed by 1,2-diamino-
cyclohexane (1 mL, 8 mmol) and bromobenzene (6.2 mL, 60 mmol) were
added to a mixture of CuI (0.38 g, 2 mmol), indole (4.6 g, 40 mmol), and
K3PO4 (17.6 g, 42 mmol). The mixture was stirred for 24 h at 1108C, and
then diluted with ethyl acetate (30 mL). The blue precipitate was re-
moved by filtration through a plug of silica to give a yellow solution.
Concentration under vacuum gave rise to an orange oil that was subject-
ed to column chromatography (silica, ethyl acetate/hexane 10/90) to
afford the pure product as a yellow liquid (6.85 g, 35 mmol). Yield: 85%;
1H NMR (400 MHz, CDCl3): d=7.43 6.88 (m, 10H), 6.45 ppm (d,
3J(H,H)=4.7 Hz, 1H); 13C NMR (101 MHz, CDCl3): d=140.0, 136.1,
130.8, 129.8, 128.2, 124.6, 122.6, 121.4, 120.6, 110.7, 103.8 ppm; MS (EI,
70 eV): m/z (%): 193 (100) [M+], 165 (18), 89 (9), 77 (6); HRMS: calcd
for C14H11N: 193.08914; found: 193.08791.
d=7.58 (m, 1H), 7.42 7.33 (m, 3H), 7.15 (m, 2H), 6.98 (m, 3H), 6.82 (m,
1H), 1.89 1.55 ppm (m, 30H); 13C NMR (101 MHz, CD2Cl2): d=141.8,
141.2, 137.2, 136.5, 132.6 (d, 2J(C,P)=2.9 Hz), 131.2, 130.2, 130.0, 124.5,
122.8, 122.3, 114.3 (d, 1J(C,P)=5.7 Hz), 43.8 (d, 1J(C,P)=12.4 Hz), 39.7,
35.2 (d, 2J(C,P)=8.6 Hz), 33.9 ppm; 31P NMR (162 MHz, CD2Cl2): d=
6.05 ppm; IR (KBr): n˜ =3054.7, 2903.2, 2846.9, 1597.1, 1498.1, 1448.6,
1342.6, 1209.8, 731.1, 649.1 cmÀ1; MS (EI, 70 eV): m/z (%): 493 (46) [M+
], 358 (16), 135 (100), 93 (16); HRMS: calcd for C34H40NP: 493.28983;
found: 493.28781.
Catalytic amination of aryl chlorides: A 30 mL pressure tube was loaded
with Pd(OAc)2 (5.6 mg, 0.025 mmol), the ligand (0.050 mmol), and
NaOtBu (577 mg, 6.0 mmol) and was purged by argon. Then, toluene
(5 mL), the aryl chloride (5 mmol) and the amine (6 mmol) were added
successively under argon. The mixture was stirred for 20 h at 1208C.
After cooling to room temperature the mixture was diluted with diethyl
ether (15 mL) and washed with water (10 mL). The organic phase was
dried over MgSO4, concentrated under vacuum and the product was iso-
Synthesis of N-phenylindole-based phosphine ligands: In a three-necked
100 mL round-bottomed flask equipped with a reflux condenser, N-phe-
nylindole (2.9 g, 15 mmol) was dissolved in toluene (30 mL) under argon.
2988
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 2983 2990

Palladium-Catalyzed Amination
2983 2990
lated by column chromatography (silica, ethyl acetate/hexane 10:90). Al-
ternatively, diethylene glycol di-n-butyl ether or hexadecane was added
as an internal standard and quantitative analysis was performed by using
gas chromatography. The commercially available products were identified
by comparison of their GC-MS data with the data of authentic samples;
known products were characterized by NMR and mass spectroscopy, un-
known products were characterized by NMR, IR, MS, and high-resolu-
tion MS (HRMS) spectroscopy.
Diphenylamine: MS (EI, 70 eV): m/z (%): 169 (100) [M+], 84 (17), 77
(12), 51 (12).
N-Phenylmorpholine: MS (EI, 70 eV): m/z (%): 163 (85) [M+], 105
(100), 77 (27).
N-n-Butyl-4-anisidine: Pale yellow liquid; 1H NMR (400 MHz, CDCl3):
d=6.72 (d, 3J(H,H)=8.9 Hz, 2H), 6.51 (d, 3J(H,H)=8.9 Hz, 2H), 3.22
(brs, 1H), 3.68 (s, 3H), 2.99 (t, 3J(H,H)=7.1 Hz, 2H), 1.52 (m, 2H),
1.37 ppm (m, 2H), 0.90 (t, 3J(H,H)=7.3 Hz, 3H); 13C NMR (101 MHz,
CDCl3): d=152.4, 143.4, 115.3, 114.4, 56.2, 45.1, 32.2, 20.8, 14.4 ppm; MS
(EI, 70 eV): m/z (%): 179 (55) [M+], 136 (100).
N-(4-Methoxyphenyl)-N-methylaniline: Yellow oil; 1H NMR (400 MHz,
CDCl3): d=7.60 (m, 2H), 7.49 (d, 3J(H,H)=9.1 Hz, 2H), 7.29 (d,
3J(H,H)=8.9 Hz, 2H), 7.19 (m, 3H), 4.18 (s, 3H), 3.65 ppm (s, 3H); 13C
NMR (101 MHz, CDCl3): d=156.8, 150.3, 142.7, 129.5, 126.7, 118.9,
116.3, 115.3, 55.9, 41.0 ppm; MS (EI, 70 eV): m/z (%): 213 (31) [M+],
198 (100), 77 (12).
N-Methyl-N-[4-(trifluoromethyl)phenyl]aniline: Yellow oil; 1H NMR
(400 MHz, CDCl3): d=7.69 (m, 4H), 7.48 (m, 3H), 7.13 (d, 3J(H,H)=
8.7 Hz, 2H), 3.62 ppm (s, 3H); 13C NMR (101 MHz, CDCl3): d=152.0,
148.2, 130.3, 126.7 (q, 3J(C,F)=3.8 Hz), 125.8, 125.4, 120.3 (q, 2J(C,F)=
32.4 Hz), 115.3, 40.6 ppm; 19F NMR (235.4 MHz, CDCl3): d=À60.6 ppm;
MS (EI, 70 eV): m/z (%): 251 (100) [M+], 77 (24).
N-n-Butylaniline: MS (EI, 70 eV): m/z (%): 149 (17) [M+], 106 (100), 77
(17).
Methyldiphenylamine: MS (EI, 70 eV): m/z (%): 183 (100) [M+], 167
(27), 104 (10), 91 (9), 77 (21), 51 (9).
Triphenylamine: MS (EI, 70 eV): m/z (%): 245 (100) [M+], 167 (2), 77
(12).
N-Methyl-N-[3-(trifluoromethyl)phenyl]aniline: Yellow liquid; 1H NMR
(400 MHz, CDCl3): d=7.33 7.13 (m, 3H), 7.04 6.92 (m, 6H), 3.27 ppm
(s, 3H); 13C NMR (101 MHz, CDCl3): d=149.8, 148.5, 131.8 (q,
2J(C,F)=31.8 Hz), 130.1, 129.8, 124.7 (q, 1J(C,F)=272 Hz), 124.2, 123.9,
120.8, 116.3 (q, 3J(C,F)=3.8 Hz), 113.9 (q, 3J(C,F)=3.8 Hz), 40.7 ppm;
19F NMR (235.4 MHz, CDCl3): d=À62.6 ppm; MS (EI, 70 eV): m/z (%):
251 (100) [M+], 145 (9), 77 (17); HRMS: calcd for C14H12NF3: 251.09218;
found: 251.09357.
N-(2,4-Difluorophenyl)-N-methylaniline: Yellow liquid; 1H NMR
(400 MHz, CDCl3): d=7.13 (m, 3H), 6.80 (m, 2H), 6.69 (m, 1H), 6.59
(m, 2H), 3.14 ppm (s, 3H); 13C NMR (101 MHz, CDCl3): d=160.9 (dd,
1J(C,F)=147.9 Hz, 3J(C,F)=11.4 Hz), 179.4 (dd, 1J(C,F)=252.7 Hz,
3J(C,F)=12.4 Hz), 132.5 (dd, 2J(C,F)=11.4 Hz, 4J(C,F)=3.8 Hz), 149.1,
130.4 (dd, 3J(C,F)=11.4 Hz, 3J(C,F)=9.5 Hz), 129.5, 114.3, 118.8, 112.3
(dd, 2J(C,F)=21.9 Hz, 4J(C,F)=3.8 Hz), 105.7 (dd, 2J(C,F)=26.7 Hz,
2J(C,F)=24.7 Hz), 39.3 ppm; 19F NMR (235.4 MHz, CDCl3): d=À112.6,
À115.6 ppm; IR (Nujol): n˜ =3064.7, 2926.7, 2616.1, 1600.2, 1508.5, 1287.3,
1259.8, 1139.9, 965.5, 875.6, 715.0, 692.1 cmÀ1; MS (EI, 70 eV): m/z (%):
219 (100) [M+], 203 (15), 178 (7), 140 (13), 77 (12); HRMS: calcd for
C13H11NF2: 219.08595; found: 219.08524.
N-(2-Pyridyl)morpholine: Yellow liquid; 1H NMR (400 MHz, CDCl3):
d=7.41 (m, 2H), 6.57 (m, 2H), 3.74 (m, 4H), 3.41 ppm (m, 4H); 13C
NMR (101 MHz, CDCl3): d=160.0, 148.4, 137.9, 114.2, 107.4, 67.2,
46.0 ppm; MS (EI, 70 eV): m/z (%): 164 (50) [M+], 133 (66), 107 (44), 79
(100).
N-(2-Pyridyl)-2-toluidine: White solid; 1H NMR (400 MHz, CDCl3): d=
8.09 (m, 1H), 7.36 (m, 2H), 7.18 6.55 (m, 5H), 6.34 (brs, 1H), 2.20 ppm
(s, 3H); 13C NMR (101 MHz, CDCl3): d=157.2, 148.9, 138.9, 138.1, 131.8,
131.5, 127.2, 124.8, 123.3, 115.6, 107.9, 18.4 ppm; MS (EI, 70 eV): m/z
(%): 184 (38) [M+], 169 (100), 91 (13), 78 (11); HRMS: calcd for
C12H12N2: 184.10005; found: 184.09990.
N-Phenyl-2-toluidine: Yellow liquid; 1H NMR (400 MHz, CDCl3): d=
7.29 7.15 (m, 5H), 6.95 (m, 4H), 5.39 (brs, 1H), 2.28 ppm (s, 3H); 13C
NMR (101 MHz, CDCl3): d=144.1, 141.4, 131.1, 129.5, 128.5, 126.9,
122.2, 120.6, 118.9, 117.6, 18.1 ppm; MS (EI, 70 eV): m/z (%): 183 (100)
[M+], 106 (20), 91 (18).
1
N-n-Butyl-2-toluidine: Colorless liquid; H NMR (400 MHz, CDCl3): d=
6.99 (m, 1H), 6.91 (m, 1H), 6.50 (m, 2H), 3.25 (brs, 1H), 3.00 (t,
3J(H,H)=7.0 Hz, 2H), 1.98 (s, 3H), 1.51 (m, 2H), 1.32 (m, 2H),
0.85 ppm (t, 3J(H,H)=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3): d=
145.3, 128.9, 126.1, 120.5, 115.5, 108.5, 42.6, 30.7, 19.4, 16.4, 12.9 ppm; MS
(EI, 70 eV): m/z (%): 163 (40) [M+], 120 (100), 91 (20).
1
N-n-Butyl-3-toluidine: Colorless liquid; H NMR (400 MHz, CDCl3): d=
6.96 (m, 1H), 6.42 (m, 1H), 6.31 (m, 2H), 3.34 (brs, 1H), 2.99 (t,
3J(H,H)=7.0 Hz, 2H), 2.18 (s, 3H), 1.49 (m, 2H), 1.33 (m, 2H),
0.86 ppm (t, 3J(H,H)=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3): d=
149.1, 139.4, 129.6, 118.5, 113.9, 110.4, 44.2, 32.2, 22.1, 20.8, 14.4 ppm; MS
(EI, 70 eV): m/z (%): 163 (40) [M+], 120 (100), 91 (20).
N-n-Butyl-4-toluidine: Light yellow liquid; 1H NMR (400 MHz, CDCl3):
d=6.89 (d, 3J(H,H)=7.9 Hz, 2H), 6.43 (d, 3J(H,H)=8.5 Hz, 2H), 3.26
3
(brs, 1H), 2.97 (t, J(H,H)=7.1 Hz, 2H), 2.14 (s, 3H), 1.48 (m, 2H), 1.32
(m, 2H), 0.85 ppm (t, 3J(H,H)=7.3 Hz, 3H); 13C NMR (101 MHz,
CDCl3): d=146.6, 129.9, 126.5, 113.1, 44.3, 31.9, 20.6, 20.5, 14.2 ppm; MS
(EI, 70 eV): m/z (%): 163 (30) [M+], 120 (100), 91 (15).
N-n-Butyl-2,6-dimethylaniline: Colorless liquid; 1H NMR (400 MHz,
CDCl3): d=6.88 (d, 3J(H,H)=7.5 Hz, 2H), 6.70 (t, 3J(H,H)=7.4 Hz,
3
1H), 3.36 (brs, 1H), 2.88 (t, J(H,H)=7.0 Hz, 2H), 2.18 (s, 6H), 1.47 (m,
2H), 1.32 (m, 2H), 0.85 ppm (t, 3J(H,H)=7.3 Hz, 3H); 13C NMR
(101 MHz, CDCl3): d=146.9, 129.6, 129.3, 122.0, 48.5, 33.9, 20.9, 19.0,
14.5 ppm; MS (EI, 70 eV): m/z (%): 177 (40) [M+], 134 (100), 105 (20).
1
N-Methyl-N-phenyl-2-toluidine: Yellow oil; H NMR (400 MHz, CDCl3):
N-Benzyl-N’-(2-pyridyl)piperazine: Yellow solid; 1H NMR (400 MHz,
CDCl3): d=8.10 (m, 1H), 7.37 (m, 1H), 7.29 7.17 (m, 5H), 6.53 (m, 2H),
3.48 (s, 2H), 3.46 (m, 4H), 2.74 2.49 ppm (m, 4H); 13C NMR (101 MHz,
CDCl3): d=160.0, 148.4, 138.4, 137.8, 129.6, 128.7, 127.6, 113.6, 107.4,
63.6, 53.4, 45.6; MS (EI, 70 eV): m/z (%): 253 (25) [M+], 159 (27), 146
(39), 107 (100), 91 (64), 78 (17).
d=7.72 7.56 (m, 6H), 7.14 (m, 1H), 6.97 (m, 2H), 3.65 (s, 3H), 2.58 ppm
(s, 3H); 13C NMR (101 MHz, CDCl3): d=149.6, 147.3, 137.3, 131.8, 129.4,
128.8, 127.9, 129.9, 117.3, 113.3, 39.5, 18.3 ppm; MS (EI, 70 eV): m/z (%):
197 (100) [M+], 182 (43), 167 (21), 77 (20).
1
N-Methyl-N-phenyl-3-toluidine: Yellow oil; H NMR (400 MHz, CDCl3):
d=7.66 7.53 (m, 4H), 7.41 7.17 (m, 5H), 3.67 (s, 3H), 2.69 ppm (s, 3H);
13C NMR (101 MHz, CDCl3): d=149.7, 149.6, 139.5, 129.7, 128.8, 125.9,
122.0, 121.5, 120.6, 118.5, 40.8, 22.1 ppm; MS (EI, 70 eV): m/z (%): 197
(100) [M+], 167 (10), 77 (12).
N-(2,5-Dimethylphenyl)-N-methylaniline: Yellow liquid; 1H NMR
(400 MHz, CDCl3): d=7.06 (m, 3H), 6.88 (m, 2H), 6.59 (m, 1H), 6.43
(m, 2H), 3.10 (s, 3H), 2.19 (s, 3H), 1.99 ppm (s, 3H); 13C NMR
(101 MHz, CDCl3): d=149.7, 147.1, 137.7, 133.9, 131.6, 129.5, 129.3,
127.7, 117.2, 113.3, 39.5, 21.4, 17.9 ppm; MS (EI, 70 eV): m/z (%): 211
(100) [M+], 196 (56), 181 (41), 134 (7), 91 (11), 77 (15).
N-(4-Cyanophenyl)morpholine: Pale yellow solid; 1H NMR (400 MHz,
CDCl3): d=7.76 (d, 3J(H,H)=9.1 Hz, 2H), 7.11 (d, 3J(H,H)=9.1 Hz,
2H), 4.09 (m, 4H), 3.52 ppm (m, 4H); 13C NMR (101 MHz, CDCl3): d=
153.9, 133.9, 129.3, 120.3, 144.5, 66.9, 47.7 ppm; MS (EI, 70 eV): m/z (%):
188 (56) [M+], 130 (100), 102 (24).
N-(6-Methoxy-2-pyridyl)morpholine: Light brown liquid; 1H NMR
(400 MHz, CDCl3): d=7.40 (t, 3J(H,H)=7.9 Hz, 1H), 6.12 (m, 2H), 3.86
(s, 3H), 3.80 (m, 4H), 3.47 ppm (m, 4H); 13C NMR (101 MHz, CDCl3):
d=163.5, 158.8, 140.5, 99.3, 99.2, 67.1, 53.4, 46.0 ppm; IR (Nujol): n˜ =
2964.2, 2893.5, 2852.7, 1590.9, 1444.6, 1414.1, 1264.1, 1239.0, 1033.0, 985.8,
780.5 cmÀ1; MS (EI, 70 eV): m/z (%): 194 (63) [M+], 137 (31), 109 (100);
HRMS: calcd for C10H14N2O2: 194.10553; found: 194.10446.
N-Benzyl-N’-(2-quinolyl)piperazine: Yellow solid; 1H NMR (400 MHz,
CDCl3): d=7.78 (d, 3J(H,H)=9.1 Hz, 1H), 7.61 (d, 3J(H,H)=8.5 Hz,
3
1H), 7.50 (d, J(H,H)=8.3 Hz, 1H), 7.45 (m, 1H), 7.21 (m, 6H), 6.87 (d,
3J(H,H)=9.3 Hz, 1H), 3.68 (t, 3J(H,H)=5.1 Hz, 4H), 3.49 (s, 2H),
2.51 ppm (t, 3J(H,H)=5.1 Hz, 4H); 13C NMR (101 MHz, CDCl3): d=
157.9, 148.3, 137.8, 129.9, 129.7, 128.7, 127.6, 127.0, 123.5, 122.7, 109.9,
63.6, 53.5, 44.5 ppm; MS (EI, 70 eV): m/z (%): 303 (11) [M+], 157 (100),
128 (18), 91 (32).
Chem. Eur. J. 2004, 10, 2983 2990
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2989

M. Beller et al.
FULL PAPER
N-Methyl-N-(3-pyridyl)aniline: Light yellow oil; 1H NMR (400 MHz,
CDCl3): d=8.20 (d, 4J(H,H)=2.6 Hz, 1H), 8.02 (m, 1H), 7.18 (m, 2H),
7.10 (m, 1H), 6.97 (m, 4H), 3.19 ppm (s, 3H); 13C NMR (101 MHz,
CDCl3): d=148.3, 145.5, 141.6, 130.0, 128.7, 125.1, 123.8, 123.7, 122.8,
40.4 ppm; MS (EI, 70 eV): m/z (%): 184 (100) [M+], 168 (19), 77 (20).
1456; Angew. Chem. Int. Ed. Engl. 1995, 34, 1348; c) A. S. Guram,
S. L. Buchwald, J. Am. Chem. Soc. 1994, 116, 7901; d) for the first
palladium-catalyzed amination of aryl chlorides see: M. Beller, T. H.
Riermeier, C.-P. Reisinger, W. A. Herrmann, Tetrahedron Lett. 1997,
38, 2073.
1
[6] a) B. C. Hamann, J. F. Hartwig, J. Am. Chem. Soc. 1998, 120, 7369;
b) J. P. Wolfe, S. Wagaw, S. L. Buchwald, J. Am. Chem. Soc. 1996,
118, 7215.
[7] a) G. Mann, J. F. Hartwig, M. S. Driver, C. Fernµndez-Rivas, J. Am.
Chem. Soc. 1998, 120, 827; b) M. S. Driver, J. F. Hartwig, J. Am.
Chem. Soc. 1996, 118, 7217.
[8] a) M. Nishiyama, T. Yamamoto, Y. Koie, Tetrahedron Lett. 1998, 39,
617; b) for an excellent review on palladium-catalyzed functionaliza-
tions of aryl chloride see: A. F. Littke, G. C. Fu, Angew. Chem.
2002, 114, 4350; Angew. Chem. Int. Ed. 2002, 41, 4176.
[9] J. P. Wolfe, S. L. Buchwald, Angew. Chem. 1999, 111, 2570; Angew.
Chem. Int. Ed. 1999, 38, 2413.
N-Methyl-N-phenyl-3-(2-hydroxyethyl)aniline: Light yellow oil; H NMR
(400 MHz, CDCl3): d=7.6 (m, 2H), 7.5 (m, 1H), 7.36 (m, 2H), 7.29 (m,
1H), 7.2 (m, 2H), 7.13 (m, 1H), 4.14 (t, 3J(H,H)=6.54 Hz, 2H), 3.63 (s,
3H), 3.12 (t, 3J(H,H)=6.54 Hz, 2H), 1.95 ppm (brs, 1H); 13C NMR
(101 MHz, CDCl3): d=149.38, 149.04, 139.68, 129.43, 129.36, 121.75,
121.69, 121.02, 120.61, 118.21, 63.73, 40.39, 39.42 ppm; IR (neat): n˜ =
3355.2, 3026.8, 2937.1, 2874.1, 1593.9, 1582.6, 1494.9, 1345.6, 1258, 1045.5,
992.7, 874.2, 752.3, 696.6, 599.1, 571.5 cmÀ1; MS (EI, 70 eV): m/z (%): 227
(100) [M+], 196 (19), 181 (23), 167 (8), 105 (11), 91 (17), 77 (17); HRMS:
calcd for C15H18NO: 228.13884; found: 228.13979.
[10] This ligand is now commercially available by Strem and Degussa
¾
Homogeneous Catalysts under the tradename cataCXium A. For
Acknowledgements
other applications see: a) A. Zapf, A. Ehrentraut, M. Beller, Angew.
Chem. 2000, 112, 4315; Angew. Chem. Int. Ed. 2000, 39, 4153; b) A.
Ehrentraut, A. Zapf, M. Beller, Synlett 2000, 1589; c) A. Ehrentraut,
A. Zapf, M. Beller, Adv. Synth. Catal. 2002, 344, 209; d) A. Tewari,
M. Hein, A. Zapf, M. Beller, Synthesis 2004, in press; e) A. Kˆllhof-
er, T. Pullmann, H. Plenio, Angew. Chem. 2003, 115, 1086; Angew.
Chem. Int. Ed. 2003, 42, 1056.
We acknowledge financial support from the State of Mecklenburg-Vor-
pommern, Degussa AG, and the Fonds der Chemischen Industrie (FCI).
Prof. Dr. M. Michalik, Dr. C. Fischer, C. Mewes, H. Baudisch, and S.
Buchholz are thanked for their excellent analytical support.
[11] A. Ehrentraut, A. Zapf, M. Beller, J. Mol. Catal. 2002, 182/183, 515.
[12] a) M. S. Viciu, R. F. Germaneau, O. Navarro-Fernandez, E. D. Ste-
vens, S. P. Nolan, Organometallics 2002, 21, 5470; b) A. C. Hillier,
G. A. Grasa, M. S. Viciu, H. M. Lee, C. Yang, S. P. Nolan, J. Organo-
met. Chem. 2002, 653, 69; c) M. S. Viciu, R. M. Kissling, E. D. Ste-
vens, S. P. Nolan, Org. Lett. 2002, 4, 2229; d) G. A. Grasa, M. S.
Viciu, J. Huang, S. P. Nolan, J. Org. Chem. 2001, 66, 7729; e) J.
Huang, G. A. Gabriella, S. P. Nolan, Org. Lett. 1999, 1, 1307.
[13] A. Frisch, A. Zapf, O. Briel, B. Kayser, N. Shaikh, M. Beller, J. Mol.
Catal. 2004, 214, 231.
[14] For some early work see: a) M. Beller, H. Fischer, W. A. Herrmann,
C. Bro˚mer, Angew. Chem. 1995, 107, 1992; Angew. Chem. Int. Ed.
Engl. 1995, 34, 1848; b) W. A. Herrmann, C. Bro˚mer, C.-P. Reising-
er, K. ÷fele, M. Beller, T. H. Riermeier, Chem. Eur. J. 1997, 3, 1357;
for reviews see: c) M. Beller, A. Zapf, Top. Catal. 2002, 19, 101;
d) M. Beller, A. Zapf, W. M‰gerlein, Chem. Eng. Technol. 2001, 24,
575; e) J. G. de Vries, Can. J. Chem. 2001, 79, 1086.
[1] Reviews: a) J. F. Hartwig in Handbook of Organopalladium Chemis-
try for Organic Synthesis, Vol. 1 (Ed.: E.-I. Negishi), Wiley-Inter-
science, New York, 2002, p. 1051; b) J. F. Hartwig, Angew. Chem.
1998, 110, 2154; Angew. Chem. Int. Ed. 1998, 37, 2047; c) B. H.
Yang, S. L. Buchwald, J. Organomet. Chem. 1999, 576, 125;
d) P. W. N. M. van Leeuwen, P. C. J. Kamer, J. N. H. Reek, R. Dier-
kes, Chem. Rev. 2000, 100, 2741.
[2] Recent examples of Buchwald Hartwig amination reactions: Buch-
wald group: a) D. Zim, S. L. Buchwald, Org. Lett. 2003, 5, 2413;
b) M. H. Ali, S. L. Buchwald, J. Org. Chem. 2001, 66, 2560; c) X.-X.
Zhang, J. P. Sadighi, T. W. Mackewitz, S. L. Buchwald, J. Am. Chem.
Soc. 2000, 122, 7606; d) J. P. Wolfe, H. Tomori, J. P. Sadighi, J. Yin,
S. L. Buchwald, J. Org. Chem. 2000, 65, 1158; e) J. P. Wolfe, S. L.
Buchwald, J. Org. Chem. 2000, 65, 1144; Hartwig group: f) M. W.
Hopper, M. Utsunomiya, J. F. Hartwig, J. Org. Chem. 2003, 68, 2961;
g) J. P. Stambuli, R. Kuwano, J. F. Hartwig, Angew. Chem. 2002, 114,
4940; Angew. Chem. Int. Ed. 2002, 41, 4746; h) R. Kuwano, M. Utsu-
nomiya, J. F. Hartwig, J. Org. Chem. 2002, 67, 6479; i) N. Kataoka,
Q. Shelby, J. P. Stambuli, J. F. Hartwig, J. Org. Chem. 2002, 67, 5553;
j) L. M. Alcazar-Roman, J. F. Hartwig, J. Am. Chem. Soc. 2001, 123,
12905; k) S. Lee, M. Jorgensen, J. F. Hartwig, Org. Lett. 2001, 3,
2729; l) L. Alcazar-Roman, J. F. Hartwig, A. Rheingold, L. M.
Liable-Sands, I. A. Guzei, J. Am. Chem. Soc. 2000, 122, 4618; other
groups: m) D. Michalik, K. Kumar, W. F. Lo, A. Tillack, A. Zapf, M.
Arlt, T. Heinrich, M. Beller, Tetrahedron Lett. 2004, 45, 2057; n) S.
Urgaonkar, J.-H. Xu, J. G. Verkade, J. Org. Chem. 2003, 68, 8416;
o) A. Schnyder, A. F. Indolese, M. Studer, H.-U. Blaser, Angew.
Chem. 2002, 114, 3820; Angew. Chem. Int. Ed. 2002, 41, 3668;
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Received: December 15, 2003
Published online: April 28, 2004
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