Dialkylphosphinoimidazoles as new ligands for palladium-catalyzed coupling reactions of aryl chlorides

Article abstract of DOI:10.1002/adsc.200404213

N-Aryl-2-(dialkylphosphino)imidazoles and -benzimidazoles are conveniently prepared in one step from the corresponding heterocycles by selective deprotonation and quenching with chlorophosphines. The novel ligands are easily tunable and show good to excellent performance in palladium-catalyzed Suzuki reactions and Buchwald-Hartwig aminations of aryl and heteroaryl chlorides.

Full text of DOI:10.1002/adsc.200404213

FULL PAPERS
Dialkylphosphinoimidazoles as New Ligands for
Palladium-Catalyzed Coupling Reactions of Aryl Chlorides
Surendra Harkal,a Franck Rataboul,a Alexander Zapf,a Christa Fuhrmann,a
Thomas Riermeier,b Axel Monsees,b Matthias Bellera,*
a
Leibniz-Institut für Organische Katalyse an der Universität Rostock e.V. (IfOK), Buchbinderstr. 5-6,
18055 Rostock, Germany
Fax: (þ49)-381-466-9324, e-mail: matthias.beller@ifok.uni-rostock.de
b
Degussa Homogeneous Catalysts (DHC), Rodenbacher Chaussee 4, Geb. 97, 63457 Hanau, Germany
Received: July 5, 2004; Accepted: September 27, 2004
Abstract: N-Aryl-2-(dialkylphosphino)imidazoles and reactions and Buchwald–Hartwig aminations of aryl
-benzimidazoles are conveniently prepared in one and heteroaryl chlorides.
step from the corresponding heterocycles by selective
deprotonation and quenching with chlorophosphines.
The novel ligands are easily tunable and show good to Keywords: amination; aryl chlorides; homogeneous
excellent performance in palladium-catalyzed Suzuki catalysis; palladium; phosphines; Suzuki reaction
Introduction
theses must still occur. Efforts to substitute costly start-
ing materials such as aryl iodides or triflates by econom-
Palladium-catalyzed coupling reactions of aryl halides ically more attractive chloroarenes, reduction of catalyst
offer numerous interesting possibilities for fine chemi- concentration, etc. are to be seen in this respect. Anoth-
cals synthesis.[1] Based on methodological developments er important factor for further application of palladium-
achieved by a number of academic (and industrial) catalyzed coupling reactions is the development of more
groups since the early 1970s various industrial processes, efficient and economically attractive catalysts. There ex-
which are based on this chemistry, have been intro- ists still a clear need for cheap available ligands which
duced. The rapid increase both on laboratory but also in- lead to highly active catalyst systems, which are easily
dustrial scale is seen by the fact that at the end of the tunable and allow for easy scale-up.
1980s only one or two refinement reactions of aryl hal-
Here, we report the synthesis and application of novel
ides have been commercialized, while nowadays more phosphine ligands, N-aryl-2-(dialkylphosphino)imida-
than 20 processes have been used or are applied in indus- zoles, which fulfill these criteria. Various N-aryl-2-(di-
try.[2] The main advantages of these coupling processes alkylphosphino)imidazoles (Figure 1) can be synthe-
compared to classic aromatic functionalization reac- sized in only 1 or 2 reaction steps on multi-g to kg scales.
tions are the ready availability of the starting materials, All of the prepared ligands show good to excellent cata-
the generality of the methods and the broad tolerance of lyst performance in two widely-used palladium-cata-
the palladium catalysts with various functional groups.
lyzed coupling reactions, the Suzuki and Buchwald–
In order to apply more and more of these reactions in Hartwig amination reactions.
the fine chemical industry further significant cost reduc-
tions of the generally developed laboratory-scale syn- as intermediates for the synthesis of pharmaceuticals,
agrochemicals and new materials, we have chosen
cross-coupling reactions of aryl halides with arylboronic
acids (Suzuki reaction)[3] and primary or secondary
amines (Buchwald–Hartwig amination)[4] as test reac-
tions of our ligands. Clearly, these methods have been
significantly improved in the last decade and have
been intensively studied and applied in organic syn-
thesis.
Due to the importance of biaryls and aromatic amines
Although even metal-free Suzuki reactions of aryl
bromides and iodides are known,[5] less reactive, but
Figure 1. N-Aryl-2-(dialkylphosphino)imidazoles
commercially attractive, chloroarenes cannot be cou-
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DOI: 10.1002/adsc.200404213
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Dialkylphosphinoimidazoles as New Ligands
FULL PAPERS
Scheme 1. General synthesis of N-aryl-2-(dialkylphosphino)-
imidazoles and N-aryl-2-(dialkylphosphino)benzimidazoles.
Scheme 2. Palladium-catalyzed reaction of chlorobenzene
and aniline.
pled under these conditions. Notable recent catalyst de-
velopments for the use of aryl chlorides[6] have been re-
ported by Bedford,[7] Buchwald,[8] Fu,[9] Herrmann,[10]
Nolan,[11] us,[12] and others.[13] In addition, our group
has reported the use of di-(1-adamantyl)-n-butylphos-
phine[12c,14] and N-aryl-2-(dialkylphosphino)pyrrole/in-
dole as highly active ligands for the coupling of a wide
range of aryl chlorides with phenylboronic acid[12a] and
amines,[15] respectively. Nevertheless, there is a continu-
ous interest in efficient but more practical new ligands.
Table 1. Amination of chlorobenzene with aniline using li-
gands 1–4.
Entry Ligand Conversion [%][a] Yield [%][a] TON[a]
1
1
2
2
3
4
88
87
99
99
92
99
174
198
198
182
198
2
100
100
92
3[b]
4
5
100
Reaction conditions: 5 mmol chlorobenzene, 6 mmol aniline,
6 mmol NaO-t-Bu, 0.5 mol % Pd(OAc)2, 1 mol % ligand,
5 mLtoluene, 48 h, 120 8C. Reaction time has not been mini-
mized.
Results and Discussion
[a]
Average of two runs, determined by GC using diethylene
By virtue of the most acidic proton at the C-2 position in
the imidazole ring and similar to our previous report on
N-aryl-2-(dialkylphosphino)pyrroles/indoles,[12a,15] we
synthesized the four different N-aryl-2-(dialkylphosphi-
glycol di-n-butyl ether as internal standard.
8 h.
[b]
no)imidazoles/benzimidazoles depicted in Figure 1.[16] 4 is probably due to the decreased steric bulk of the cy-
N-Mesityl-1H-imidazole was prepared by condensation clohexyl groups.
of mesitylamine, paraformaldehyde, glyoxal and ammo-
Table 2 emphasizes the general usefulness of this new
nium chloride[17] while N-arylbenzimidazoles were pre- catalyst system. Applying ligands 2 and 4 in almost all
pared by copper-catalyzed N-arylation of benzimida- cases the coupling product was obtained in good to ex-
zole.[18] The obtained N-arylated (benz)imidazoles cellent yield in the presence of 0.5 mol % Pd. Activated
were then deprotonated by a mixture of n-BuLi (electron-deficient) chloroarenes reacted also well at
(1.0 equiv.) and TMEDA (1.06 equivs.) in n-hexane or room temperature with 1 mol % Pd (Table 2, entries 1
THF. N-Mesityl-1H-imidazole was easily deprotonated and 2), while deactivated (electron-rich) substrates
at room temperature, whereas N-phenyl-1H-benzimi- gave the desired coupling products in up to 99% yield
dazole and N-naphthyl-1H-benzimidazole required at higher temperatures (Table 2, entries 4, 7–9). In addi-
careful deprotonation at a lower reaction temperature tion to secondary amines also more challenging primary
(À658C). The resulting carbanions were subsequently aliphatic amines such as n-butylamine can be coupled ef-
reacted with the corresponding dialkylchlorophos- ficiently with aryl chlorides (entry 8). More interestingly
phines giving the desired phosphines in moderate to this new catalyst system also works well with sensitive
good yields: 58% 1, 80% 2, 41% 3, and 33% 4 functionalized substrates. For example, 2-(m-chloro-
(Scheme 1).
phenyl)ethanol can be coupled smoothly with anilines
at low temperature (658C; Table 2, entry 9). Further-
more heteroaryl chlorides gave excellent yields with
Amination Reactions (Buchwald–Hartwig Amination) N-methylaniline (Table 2, entry 3), and the hindered
N-cyclohexylaniline could be coupled with chloroben-
Initially, the reaction of chlorobenzene with aniline was zene in good yield (Table 2, entry 6).
chosen to test the new ligands 1–4 (Scheme 2, Table 1).
With the dicyclohexylphosphino-substituted ligand 1 di-
phenylamine was obtained in good yield (87%; Table 1, Suzuki Coupling Reactions
entry 1), while the di-tert-butylphosphino-substituted
imidazole and benzimidazoleligands 2–4 gave evenbet- In case of Suzuki reactions the behavior of the different
ter yields of 92–99% (Table 1, entries 2–5). Entry 3 ligands was studied more closely using the model reac-
shows that the reaction is finished after 8 h (99% yield) tion of a non-activated aryl chloride (p-chlorotoluene
which corresponds to a TON of ca. 200. The somewhat with phenylboronic acid). Initially the metal/ligand ratio
lower productivity of ligand 1 compared to ligands 2– was optimized at a low catalyst loading of 0.01 mol %
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Surendra Harkal et al.
FULL PAPERS
Table 2. Palladium-catalyzed amination of various aryl chlorides.
Entry
Aryl chloride
Amine
Product
Ligand
T [ 8C]
Yield [%][a]
98
1[b]
4
25
2[b]
2
2
4
2
25
80
80
80
86
98
99
99
3
4
5
6[c]
4
2
110
80
68
99
7
8
2
4
80
65
99
60
9[d]
Reaction conditions: 5 mmol aryl chloride, 6 mmol amine, 6 mmol NaO-t-Bu, 0.5 mol % Pd(OA)2, 1 mol % ligand, 5 mLto-
luene, 20 h. Reaction time has not been minimized.
[a]
Average of 2 runs, determined by GC using diethylene glycol di-n-butyl ether or hexadecane as internal standard.
1 mol % Pd(OAc)2, 2 mol % ligand.
5 mmol amine, 6 mmol aryl chloride, 7.5 mmol NaO-t-Bu, 9 mLtoluene.
2 mmol aryl chloride, 2.4 mmol amine, 2.4 mmol NaO-t-Bu, 3 mLtoluene.
[b]
[c]
[d]
Pd(OAc)2 using ligand 3 in toluene. As shown in Table 3 It is not clear at this moment, which factors are decisive
in the presence of 0.1 mol % ligand (palladium/ligand for the ligandꢁs performance.
ratio¼1/10) 4-methylbiphenyl is obtained in 86% yield
In further experiments ligands 3 and 4 were tested in
(Table 3, entry 2). A lower ligand concentration as well the arylation of different aryl and heteroaryl chlorides
as a higher one leads to significantly reduced yields of 4- (Table 4). The corresponding biaryls were obtained in
methylbiphenyl (entries 1 and 3). Ligands 1, 2, and 4 excellent yields at low catalyst concentrations (0.01–
were also tested, but ligand 3 was the only one that 0.05 mol % Pd) in most cases. meta- and para-substitut-
gave reproducible results at low catalyst concentration. ed chloroarenes are easily coupled regardless of their
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Dialkylphosphinoimidazoles as New Ligands
FULL PAPERS
electronic nature (Table 4, entries 1–5). When
0.05 mol % Pd are applied, both ligands tested show
highly reproducible results. In this case yields are almost
the same for ligands 3 and 4. However, the coupling of
the sterically congested 2,6-dimethylchlorobenzene is
more problematic, and a different performance of
both ligands is observed. Here, 2,6-dimethylbiphenyl is
obtained in moderate yield (44%) using ligand 4 (Ta-
ble 4, entry 7). Surprisingly, the slightly slimmer ligand
3 performs even worse in this case (<20% yield). How-
ever, the less bulky 2-chlorotoluene can be coupled effi-
ciently in the presence of both ligands (90%; Table 4, en-
try 6). In addition, 3-chloropyridine provides an excel-
lent 99% of the desired product (Table 4, entry 8).
Scheme 3. Suzuki coupling of aryl chlorides.
Table 3. Suzuki reaction of p-chlorotoluene and phenylboro-
nic acid.
Entry
Ligand
Pd:L
Yield [%][a]
1
2
3
4
5
6
3
3
3
2
1
4
1: 2
57
86
79
50–83
15–66
59–95
1: 10
1: 20
1: 10
1: 10
1: 10
Conclusions
Reaction conditions: 3 mmol p-chlorotoluene, 4.5 mmol phe-
nylboronic acid, 6 mmol K3PO4, 0.01 mol % Pd(OAc)2, 6 mL
Monodentate N-aryl-2-(dialkylphosphino)imidazoles
and -benzimidazoles are conveniently synthesized by se-
toluene, 1008C, 20 h.
[a]
Determined by GC using hexadecane as internal standard. lective metallation at the 2-position of the respective
heterocycle and quenching with chlorophosphines.
This one-pot procedure should be applicable to a wide
variety of similar ligands, enabling an easy preparation
Table 4. Suzuki coupling of various aryl chlorides with phe-
of a novel class of attractive ligands for aryl-X function-
nylboronic acid.
alization reactions. The prepared ligands have been
Entry Aryl chloride Ligand Catalyst Yield TON
[mol %] [%][a]
shown to give good to very good performance in Suzuki
reactions and Buchwald–Hartwig aminationsof aryl and
heteroaryl chlorides.
1
4
0.05
95
1900
2
3
0.01
85
8500
Experimental Section
General Remarks
3
4
5
4
3
3
0.05
0.05
0.05
93
94
84
1860
1880
1680
All reactions were carried out under an argon atmosphere in
dry Schlenk flasks. All solvents were made anhydrous by stand-
ard procedures. Ligands were synthesized and stored under an
inert atmosphere using Schlenk techniques. Nevertheless, they
can be handled in air for short periods without problems. All
starting materials and reactants were used as received from
commercial suppliers, except TMEDA which was distilled
and degassed before use. NMR spectra were recorded on an
ARX 400 (Bruker) spectrometer, chemical shifts were referred
to undeuterated solvent, H3PO4 (80% in water) and CFCl3 for
1H, 13C, 31P and 19F NMR, respectively. IR spectra were record-
ed on a Magna-IR-serie 550 (Nicolet) spectrometer. Mass
spectra were recorded on an AMD 402 double focusing mag-
netic sector spectrometer (AMD Intectra). GC/MS spectra
were recorded on an HP 5989A (Hewlett Packard) chromato-
graph equipped with a quadrupole analyzer. Gas chromato-
graphic analyses were carried out on an HP 6890 (Hewlett
Packard) chromatograph using an HP 5 column.
6
7
3
4
0.05
0.05
90
44
1800
880
8
4
0.05
99
1980
Reaction conditions: 3 mmol aryl chloride, 4.5 mmol phenyl-
boronic acid, 6 mmol K3PO4, Pd :L¼1: 10, 6 mLtoluene,
1008C, 20 h.
1-Phenyl-1H-benzimidazole
In a 100-mLSchlenk flask CuI (644 mg, 10 mol %), 1,10-phe-
nanthroline (1.22 g, 20 mol %), benzimidazole (4.78 g,
[a]
Determined by GC using hexadecane as internal standard.
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Surendra Harkal et al.
2926, 2848, 1609, 1445, 1280, 1087, 1030, 854, 750, 489 cmÀ1
MS (EI, 70 eV): m/z¼382 (11), 299 (100), 217 (24), 202 (7),
185 (27), 83 (7), 55 (21), 41 (9); HRMS (CI): calcd. for
C24H36N2P: 383.26161; found: 383.25907.
FULL PAPERS
40 mmol), and Cs2CO3 (19.3 g, 59.2 mmol) were evacuated
twice and back-filled with argon. Iodobenzene (6.87 g,
33.7 mmol) and DMF (35 mL) were added. The Schlenk flask
was sealed and the reaction mixture was stirred at 1108C. After
24 h the suspension was cooled to room temperature, diluted
with ethyl acetate and filtered through a plug of silica gel, elut-
ing with ethyl acetate. The solution was concentrated and the
resulting residue was purified by column chromatography
(acetone/n-hexane) to provide the desired product as a color-
;
2-(Di-tert-butylphosphino)-N-mesitylimidazole (2)
1
In a 250-mLSchlenk flask
N-mesitylimidazole (1.86 g,
less oil; yield: 5.2 g (79%). H NMR (400 MHz, CDCl3): d¼
10 mmol) was suspended in n-hexane (50 mL). TMEDA
(1.6 mL, 10.6 mmol) and a solution of n-BuLi (1.6 M in n-hex-
ane, 6.25 mL, 10 mmol) were added at room temperature, and
the reaction mixture was refluxed for 2.5 h to get a yellow sus-
pension. A solution of chlorodi-tert-butylphosphine (10 mmol
in 10 mL n-hexane) was added slowly via addition funnel. The
mixture was further refluxed for 1 h. After cooling to room
temperature, 30 mLdegassed water were added. The aqueous
layer was extracted with n-hexane (2ꢀ10 mL) and the com-
bined organic layers were washed with degassed water
(15 mL). The solution was dried over Na2SO4 and concentrated
at room temperature to furnish a yellow viscous liquid; yield:
7.92 (s 1H), 7.72 (m, 1H), 7.40–7.33 (m, 3H), 7.28 (m, 3H),
7.15 (m, 2H); 13C NMR (101 MHz, CDCl3): d¼144.0, 142.2,
136.2, 133.6, 129.9, 127.9, 123.9, 123.6, 122.7, 120.5, 110.4.
1-(1-Naphthyl)-1H-benzimidazole
In a 100-mLSchlenk flask CuI (374 mg, 10 mol %), 1,10-phe-
nanthroline (708 mg, 20 mol %), benzimidazole (2.79 g,
23.6 mmol), and Cs2CO3 (13.4 g, 41.2 mmol) were evacuated
twice and back-filled with argon. 1-Iodonaphthalene (5.0 g,
19.7 mmol) and DMF (20 mL) were added. The Schlenk flask
was sealed and the reaction mixture was stirred at 1458C. After
48 h the suspension was cooled to room temperature, diluted
with ethyl acetate and filtered through a plug of silica gel, elut-
ing with ethyl acetate. The solution was concentrated and the
resulting residue was purified by column chromatography
(acetone/n-hexane) to provide the desired product as a color-
1
2.95 g (80%). H NMR (400 MHz, C6D6): d¼7.42 (d, 1H, J¼
1.0 Hz), 6.69 (s, 2H), 6.57 (dd, 1H, J¼1.0, 2.5 Hz), 2.08 (s,
3H), 1.96 (s, 6H), 1.30 (d, 18H, J¼12.1 Hz); 13C NMR
(101 MHz, C6D6): d¼147.6 (d, J¼23.8 Hz), 138.5, 135.3,
134.6, 130.3, 129.2, 123.5, 33.7 (d, J¼16.2 Hz), 30.7 (d, J¼
14.3 Hz), 21.2, 19.2 (d, J¼3.8 Hz); 31P NMR (162 MHz,
C6D6): d¼11.9; IR (KBr): n¼3101, 2982, 2952, 2861, 1610,
1592, 1473, 1280, 1178, 1104, 852, 750, 509 cmÀ1; MS (EI,
70 eV): m/z¼330 (44), 274 (35), 218 (100), 185 (70), 158 (20),
91 (11), 57 (81), 41 (38); HRMS: calcd. for C20H31N2P:
330.22247; found: 330.21794.
1
less oil; yield: 3.67 g (76%). H NMR (400 MHz, CDCl3): d¼
8.04 (s, 1H), 7.90 (m, 3H), 7.48 (m, 3H), 7.29 (m, 3H), 7.14
(m, 1H), 6.99 (m, 1H); 13C NMR (101 MHz, CDCl3): d¼
143.7, 143.3, 135.6, 134.4, 132.3, 129.7, 129.6, 128.4, 127.5,
127.0, 125.4, 124.9, 123.5, 122.6, 122.5, 120.4, 110.8; IR (Cap/
KBr): n¼3054, 1716, 1597, 1488, 1405, 1286, 1144, 1006, 943,
770, 632, 475 cmÀ1; MS (EI, 70 eV): m/z¼244 (100), 216 (10),
127 (9), 115 (6), 77 (4); HRMS: calcd. for C17H12N2:
244.10005; found: 244.09980.
2-(Di-tert-butylphosphino)-N-phenyl-1H-
benzimidazole (3)
In a 250-mLSchlenk flask N-phenyl-1H-benzimidazole (1.7 g,
8.76 mmol) was dissolved in 30 mLTHFand TMEDA (1.4 mL,
9.27 mmol) was added. The solution was cooled to À658C and
a solution of n-BuLi (1.6 M in n-hexane, 5.47 mL, 8.76 mmol)
was added dropwise via addition funnel. The mixture was stir-
red for 1 h at À658C. A solution of chlorodi-tert-butylphos-
phine (8.76 mmol in10 mLTHF) was added slowly via addition
funnel and the mixture was stirred for further 15 minutes at
À658C and then at room temperature for 18 h. The solvents
were removed at room temperature and the brown oily residue
2-(Dicyclohexylphosphino)-N-mesitylimidazole (1)
In a 250-mLSchlenk flask
N-mesitylimidazole (1.86 g,
10 mmol) was suspended in n-hexane (50 mL). TMEDA
(1.6 mL, 10.6 mmol) and a solution of n-BuLi (1.6 M in n-hex-
ane, 6.25 mL, 10 mmol) were added at room temperature, and
the reaction mixture was refluxed for 2.5 h to get a yellow sus-
pension. A solution of chlorodicyclohexylphosphine (10 mmol
in 10 mL n-hexane) was added slowly via addition funnel. The
mixture was further refluxed for 1 h. After cooling to room
temperature, 30 mLdegassed water were added. The aqueous
layer was extracted with n-hexane (2ꢀ10 mL) and the com-
bined organic layers were washed with degassed water
(15 mL). The solution was dried over Na2SO4 and concentrated
at room temperature to get a yellow viscous residue which was
recrystallized from n-pentane to afford a white solid in two
was dissolved in 30 mLCH Cl2 and extracted with degassed
2
water (2ꢀ20 mL). The aqueous layer was extracted with
10 mLCH Cl2 and the combined organic layers were dried
2
over Na2SO4 and concentrated at room temperature to furnish
a brown viscous residue which was recrystallized from metha-
1
nol; yield: 1.2 g (41%). H NMR (400 MHz, CDCl3): d¼7.80
(d, 1H, J¼8.1 Hz), 7.40 (m, 3H), 7.20 (m, 3H), 7.15 (m, 1H),
7.00 (m, 1H), 1.17 (d, 18H, J¼12.5 Hz); 13C NMR (101 MHz,
CDCl3): d¼155.0 (d, J¼26.7 Hz), 143.9, 137.2, 136.9, 129.2,
129.0 (d, J¼2.9 Hz), 128.6, 123.1, 122.3, 120.2, 110.7, 33.7 (d,
J¼18.1 Hz), 30.2 (d, J¼14.3 Hz); 31P NMR (162 MHz,
CDCl3): d¼9.15; IR (KBr): n¼3048, 2958, 2857, 1593, 1496,
1365, 1267, 1207, 1007, 826, 748, 699, 576 cmÀ1; MS (EI,
70 eV): m/z¼338 (36), 282 (100), 267 (19), 225 (79), 147 (13),
1
crops; yield: 2.2 g (58%). H NMR (400 MHz, C6D6): d¼7.45
(d, 1H, J¼1.0 Hz), 6.71 (s, 2H), 6.58 (dd, 1H, J¼1.0, 2.2 Hz),
2.4–1.0 (m, 31H); 13C NMR (101 MHz, C6D6): d¼147.5 (d,
J¼16.2 Hz), 138.2, 135.3, 134.9, 131.4, 129.1, 122.6, 34.5 (d,
J¼9.5 Hz), 30.8 (d, J¼10.5 Hz), 30.3 (d, J¼14.3 Hz), 27.6 (d,
J¼7.6 Hz), 27.5 (d, J¼9.5 Hz), 26.8, 20.9, 18.4 (d, J¼4.8 Hz);
31P NMR (162 MHz, C6D6): d¼ À19.1; IR (KBr): n¼3091,
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Dialkylphosphinoimidazoles as New Ligands
FULL PAPERS
107 (6), 77 (11), 57 (20), 41 (30); HRMS: calcd. for C21H27N2P:
338.19119; found: 338.19061.
(3 mmol) were added. The mixture was stirred for 20 h at
1008C. After cooling to room temperature the mixture was di-
luted with diethyl ether (10 mL) and washed with aqueous so-
dium hydroxide (1 M, 10 mL). The organic phase was dried
over Na2SO4, concentrated under vacuum and the product
was isolated by column chromatography (silica, ethyl acetate/
n-hexane). Alternatively, hexadecane was added as internal
standard and quantitative analysis was done by gas chromatog-
raphy. The commercially available products were identified by
comparison of their GC/MS data with the data of authentic
samples, known products were identified by NMR and mass
spectroscopy.
2-(Di-tert-butylphosphino)-N-(1-naphthyl)-1H-
benzimidazole (4)
In a 250-ml Schlenk flask N-(1-naphthyl)-1H-benzimidazole
(1.9 g, 7.86 mmol) was dissolved in 30 mLTHF and TMEDA
(1.25 mL, 8.26 mmol) was added. The solution was cooled to
À658C and a solution of n-BuLi (1.6 M in n-hexane,
4.91 mL, 7.86 mmol) was added dropwise via addition funnel.
The mixture was stirred for 1 h at À658C. A solution of chloro-
di-tert-butylphosphine (7.86 mmol in 15 mLTHF) was added
slowly via addition funnel and the mixture was stirred for fur-
ther 15 minutes at À658C and then at room temperature for
18 h. The solvents were removed at room temperature and
the brown oily residue was dissolved in 30 mLCH 2Cl2 and ex-
tracted with degassed water (2ꢀ20 mL). The aqueous layer
Acknowledgements
This workhas been financed by the State of Mecklenburg-West-
ern Pommerania, the Bundesministerium für Bildung und For-
schung (BMBF) and Degussa AG. We thankProf. M. Michalik,
Dr. W. Baumann, Mrs. H. Baudisch, Mrs. A. Lehmann, Mrs. C.
Mewes and Ms. K. Reincke (all IfK) for excellent analytical sup-
port.
was extracted with 10 mLCH Cl2 and the combined organic
2
layers were dried over Na2SO4 and concentrated at room tem-
perature to afford a brown viscous residue which was recrystal-
1
lized from methanol; yield: 1.0 g (33%). H NMR (400 MHz,
CDCl3): d¼7.99 (m, 3H), 7.60 (m, 1H), 7.49 (m, 2H), 7.3 (m,
2H), 7.11 (m, 2H), 6.78 (m, 1H), 1.31 (d, 9H, J¼12.2 Hz),
1.17 (d, 9H, J¼12.5 Hz); 13C NMR (101 MHz, CDCl3): d¼ References and Notes
156.4 (d, J¼27.6 Hz), 143.8, 137.5, 134.2, 133.5 (d, J¼
1.9 Hz), 130.6, 129.6, 128.3, 127.8 (d, J¼2.9 Hz), 126.7, 126.5,
[1] a) Applied Homogeneous Catalysis with Organometallic
125.1, 123.5, 123.2, 122.2, 120.2, 111.0, 33.8 (d, J¼18.1 Hz),
32.0 (d, J¼18.1 Hz), 30.4 (d, J¼14.3 Hz), 30.4 (d, J¼
14.3 Hz); 31P NMR (162 MHz, CDCl3): d¼10.43; IR (KBr):
n¼3051, 2965, 2861, 1596, 1469, 1414, 1177, 947, 826, 772,
743, 515 cmÀ1; MS (EI, 70 eV): 388 (33), 332 (49), 317 (25),
276 (100), 147 (8), 57 (26), 41 (18); HRMS: calcd. for
C25H29N2P: 388.20685; found: 388.20694.
Compounds, (Eds.: B. Cornils, W. A. Herrmann), 2nd
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Buchwald–Hartwig Amination
A 30-mLpressure tube was loaded with Pd(OAc) (5.6 mg,
2
0.025 mmol), the ligand (0.050 mmol), and NaO-t-Bu
(577 mg, 6.0 mmol) and purged with argon. Then, toluene
(5 mL), the aryl chloride (5 mmol), and the amine (6 mmol)
were added successively. The mixture was stirred for the men-
tioned time and temperature. After cooling to room tempera-
ture the mixture was diluted with diethyl ether (5 mL) and
washed with water (10 mL). The organic phase was dried
over MgSO4, concentrated under vacuum and the product
was isolated by column chromatography (silica, ethyl acetate/
n-hexane or acetone/n-hexane). Alternatively, diethylene gly-
col di-n-butyl ether or hexadecane was added as internal stand-
ard and quantitative analysis was done by gas chromatography.
The commercially available products were identified by com-
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ples, known products were identified by NMR and mass spec-
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Suzuki Reaction
A 30-mLpressure tube was loaded with Pd(OAc) 2, the ligand,
K3PO4 (6 mmol), and phenylboronic acid (4.5 mmol) and was
purged with argon. Then, toluene (6 mL) and the aryl chloride
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Adv. Synth. Catal. 2004, 346, 1742–1748