Palladium(II)-Catalyzed One-Pot Syntheses of 9-(Pyridin-2-yl)-9H-carbazoles through a Tandem C-H Activation/C-X (X=C or N) Formation Process

Article abstract of DOI:10.1002/chem.201101528

A new one-pot synthesis of 9-(pyridin-2-yl)-9H-carbazoles through the simultaneous C-H activation and palladium(II)-catalyzed cross-coupling of N-phenylpyridin-2-amines with potassium aryltrifluoroborates is presented. Silver acetate and 1,4-dioxane proved to be the best oxidant and solvent, respectively. The product yields fluctuated from modest to excellent and the reaction showed sufficient functional group tolerance. p-Benzoquinone served as an important ligand for the transmetalation and reductive elimination steps in the catalytic process. The kinetic isotope effects (k_H/k_D) for the first and second C-H activation/C-C or C-N formation steps were measured as 2.14 and 1.18, respectively. Finally, a rational catalytic mechanism is presented based on all experimental evidence. Thrown together to perform: A variety of N-pyridylcarbazoles were synthesized through concurrent C-H activation/coupling of N-phenylpyridin-2-amines with potassium aryltrifluoroborates (see scheme; BQ=p-benzoquinone). The catalytic mechanism was elucidated by the examination of X-ray crystal structures of Pd^II intermediates and key products, as well as control experiments and kinetic isotope effect studies. Copyright

Full text of DOI:10.1002/chem.201101528

FULL PAPER
DOI: 10.1002/chem.201101528
Palladium(II)-Catalyzed One-Pot Syntheses of 9-(Pyridin-2-yl)-9H-
À
À
carbazoles through a Tandem C H Activation/C X (X=C or N) Formation
Process
Jean-Ho Chu, Pi-Shan Lin, Ya-Ming Lee, Wei-Ting Shen, and Ming-Jung Wu*[a]
Abstract: A new one-pot synthesis of
9-(pyridin-2-yl)-9H-carbazoles through
fluctuated from modest to excellent
and the reaction showed sufficient
functional group tolerance. p-Benzo-
quinone served as an important ligand
for the transmetalation and reductive
elimination steps in the catalytic pro-
cess. The kinetic isotope effects (kH/kD)
À
the simultaneous C H activation and
À
palladium(II)-catalyzed cross-coupling
of N-phenylpyridin-2-amines with po-
tassium aryltrifluoroborates is present-
ed. Silver acetate and 1,4-dioxane
proved to be the best oxidant and sol-
vent, respectively. The product yields
for the first and second C H activa-
À
À
tion/C C or C N formation steps were
measured as 2.14 and 1.18, respectively.
Finally, a rational catalytic mechanism
is presented based on all experimental
evidence.
À
Keywords: carbazoles · C H acti-
vation · cross-coupling · palladium ·
reaction mechanisms
Introduction
hyperiodineACTHNGUTERNNUG
(III) as catalysts.[7] To date, examples of the syn-
À
thesis of N-substituted carbazoles by C H activation have
The biaryl skeleton is a very important structural unit in nat-
ural products, synthetic pharmaceuticals, and advanced ma-
terials.[1] Many reactions for the construction of biaryls have
been developed, such as the Suzuki–Miyaura, Kumada,
Hiyama, Stille, and Negishi cross-coupling reactions.[2] Al-
though these reactions can provide high yields and chemose-
lectivity, they require additional synthetic operations to pre-
been rare.[7,8] Additionally, the development of palladi-
À
um(II)-catalyzed cascade reactions that combine direct C H
À
activation and C X (X=C or N) formation in a one-pot se-
quence is still challenging.[9] We herein present the first ex-
ample of a one-pot synthesis of 9-(pyridin-2-yl)-9H-carba-
À
zoles (4) by the tandem reaction/C H activation of N-phe-
nylpyridin-2-amine with potassium aryltrifluoroborates (2).
À
À
pare coupling reagents (Ar X and Ar M) from simple
arenes. It is, thus, necessary to develop more efficient, envi-
ronmentally friendly, and selective synthetic methodologies
for the production of biaryl compounds. In this regard, the
use of transition-metal-catalyzed direct carbon–hydrogen
bond activation/functionalization appears to be a feasible
approach to accomplish this goal.[3]
Results and Discussion
Screens of oxidants and solvents for the reaction of N-phe-
nylpyridin-2-amine (1) with potassium phenyltrifluoroborate
(2a): We initially utilized the palladium(II) acetate cata-
À
Biaryls or carbazoles are frequently selected as synthetic
targets because of their high biological activity[4] and multi-
tude of optoelectronic applications.[5] In general, they can be
synthesized by conventional methods that employ halogen-
ated biphenyl amines as starting materials. For instance, 9H-
carbazole can be easily obtained from 6’-iodobiphenyl-2-
amine in the presence of a palladium catalyst.[6] Recently,
the groups of Buchwald, Gaunt, and Chang reported syn-
thetic protocols to prepare N-substituted carbazoles directly
lyzed tandem C H activation/cross-coupling of 1 with 2a to
synthesize 4. We then began to screen various oxidants and
solvents for the catalytic reaction in the presence of co-oxi-
dant and ligand, p-benzoquinone (BQ) and DMSO at 130–
1408C for 48 h.[10] The screening results are summarized in
Table 1. Silver(I) acetate and 1,4-dioxane were found to be
the best oxidant and solvent, respectively, for the synthesis
of 4.
À
À
from 2-aminobiphenyls by C H activation/C N formation
and the use of palladium(II) acetate, copper(II) triflate, and
The catalytic reaction of 1 and other pyridine substrates 5
with 2: We subsequently carried out the reaction of 1 with a
variety of potassium aryltrifluoroborates (2), under the
aforementioned optimized reaction conditions (ArBF3K[13a]
(4 equiv), PdACTHNUTRGNEUNG
(OAc)2 (10 mol%), AgOAc[13b] (3 equiv), BQ
[a] Dr. J.-H. Chu, P.-S. Lin, Y.-M. Lee, W.-T. Shen, Prof. M.-J. Wu
Department of Chemistry, National Sun Yat-sen University
Kaohsiung, Taiwan 804 (Taiwan)
(1 equiv), and DMSO (4 equiv) at 130–1408C for 48 h in
1,4-dioxane). The results are summarized in Table 2. All re-
actions produced a mixture of 3 and 4 in modest to good
yields. Carbazoles 4 were formed as the major products in
all cases with product ratios (3/4) fluctuating between 48:52
Fax: (+886)7-5253909
E-mail: mijuwu@faculty.nsysu.edu.tw
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101528.
Chem. Eur. J. 2011, 17, 13613 – 13620
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13613

Table 1. Screens of oxidants and solvents for the catalytic reaction of 1
with 2a and Pd(OAc)2 as the catalyst.
Table 2. Synthesis of 3 and 4 by the reaction of 1 with 2 and PdACHTUNGTRENNUNG(OAc)2 as
a catalyst.
N
Entry Oxidant
Solvent
Product ratio Yield
Entry ArBF3K
Product ratio
Yield
[%][b]
3a/4a[a]
[%][b]
3/4[a]
1
2
3
4
5
6
7
8
–
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
t-butanol[12]
DMF
100:0
17:83
76:24
26:74
2:98
98:2
100:0
98:2
100:0
80:20
17:83
86:14
65:35
100:0
100:0
66:34
96:4
10
80
20
21
33
8
AgOAc
Ag2O
Ag2CO3
Cu
Cu
Hg
K2S2O8
oxone
1
80
[11]
ACHTUNGTRENNUNG
A
A
2
49
62
13
80
>99
62
52
48
46
31
21
17
9
17:83
9
10
11
12
13
14
15
16
17
18
19
20
O2
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
2
77
acetonitrile
dichloromethane
THF
DMSO
benzene
25:75
80:20
99:1
1,2-dichloroethane
1,1,2,2-tetrachloroethane 100:0
[a] The product ratio was determined by GC-MS analysis (three runs).
[b] The total yield was calculated by GC-MS analysis (three runs).
3
79
39:61
23:77
32:68
36:64
and 17:83 (calculated by GC-MS analyses of crude prod-
ucts). Finally, the structures of 4a and 3j were confirmed by
X-ray crystallography, which proved that 4 could be formed
directly from 3 (Figure 1) in a one-pot reaction.[24] Our ex-
perimental results showed that borane reagents 2, which had
neutral or electron-withdrawing groups (Table 2, entries 1–7,
48–80% yields), gave the products 3 and 4 in higher yields
than those with an electron-donating group (Table 2, en-
tries 8–10, 45–55% yields). This reaction also showed good
tolerance for halogenated arylboranes, such as fluoro,
chloro, and bromo substituents (Table 2, entries 4–6). Addi-
tionally, the reaction of various N-arylpyridine-2-amines 5
with 2a, under the optimized reaction conditions described
above, gave products 6 and 7 (Table 3). It is noteworthy that
carbazoles 7 were the major product in all cases and were
formed in excellent yields (84–95%, Table 3, entries 1–4).
Surprisingly, when N-(4-methoxyphenyl)pyridine-2-amine
(5e) was employed in this reaction, a trace amount of
adduct 7e was produced (as indicated by GC-MS analysis:
Table 3, entry 5), while, simultaneously, the starting material
5e was consumed (as indicated by thin-layer chromatogra-
phy). Extension of reaction times to 48 h did not result in
improved yields for 7e. Thus, we suspected that substrate 5e
might form a stable complex with the oxidant AgOAc.[14]
The same phenomenon was observed for substrate 5g
(Table 3, entry 7) and apparently the formation of a stable
4
5
6
75
48
70
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Palladium(II)-Catalyzed One-Pot Syntheses of Carbazoles
Table 2. (Continued)
FULL PAPER
Entry ArBF3K
Product ratio
Yield
[%][b]
3/4[a]
7
51
55
53
45
48:52
8
24:76
9
34:66
Figure 1. ORTEP drawings of a) 9-(pyridin-2-yl)-9H-carbazole (4a) and
b) N-(4’-methoxybiphenyl-2-yl)pyridin-2-amine (3j). All hydrogen atoms
of compound 3j are omitted for clarity. Ellipsoids are shown at the 50%
probability level.[24]
10
29:71
ly (Scheme 1). Therefore, the so-called directing group (pyr-
idinyl group) and the oxidant (silver acetate) may play a
special role in one-pot syntheses of N-substituted carbazoles
[a] The product ratio was calculated by GC-MS analysis (three runs).
[b] The total yield was calculated by GC-MS analysis (three runs).
À
by C H bond activation.
complex of 5e and 5g with the silver(I) ion might prevent
Investigations into the catalytic mechanism: To obtain de-
tailed information regarding the catalytic mechanism, we
synthesized the key intermediate N-phenylpyridin-2-amine
palladacycle (I)[18] in excellent yield (90%) by the reaction
À
C H activation by palladium(II) and subsequent reactions
for the formation of carbazoles 7e and 7g. Conversely,
steric effects must play a major role in the conversion of
substrate 5 f to 6 f and 7 f with extremely poor yields. Re-
cently, Shi and co-workers reported the direct ortho aryla-
tion of acetanilide 8 with trialkoxysilane reagents[15] and aryl
of 1 with a stoichiometric amount of PdACTHNUGRTNE(UNG OAc)2 in CH2Cl2 at
65–708C. The structure of I was further confirmed by X-ray
crystallography and is shown in Figure 2.[25] This structure
possesses a head-to-head U-shaped geometry (that is, two
pyridine groups that point to the same direction). This type
of palladacycle is rare because most palladacycles have a
head-to-tail U-shaped geometry.[3o,q] We carried out the re-
action of I with 2a in the presence and absence of BQ
(under the conditions depicted in Scheme 2) to verify the
importance of BQ in the catalytic reaction. We found that
4a was obtained only in the presence of BQ. The same ob-
servation was reported in our previous work[3n–p] and again
proves that BQ is an important co-ligand and co-oxidant for
the transmetalation–reductive elimination step of the cata-
lytic reaction.[19]
boronic acids[16] by C H activation, which gave the ortho-
À
arylated compounds 9 as the sole products. Recently, they
reported a stepwise method (cross-dehydrogenative aryla-
À
tion and Buchwald C N bond formation) by which acetani-
lide (8) reacted with benzene and Pd
N
lyst[17] to afford 10. Accordingly, we replaced 1 with 8 in our
optimized reaction protocol and used potassium phenyltri-
fluoroborate 2a and phenyl boronic acid as coupling re-
agents. Neither of the desired products (ortho-arylated com-
pound 9 and 10) were obtained, however, and only 8 was re-
covered (Scheme 1). In addition, the reaction of 1 with 2a
and phenyl boronic acid (under identical reaction condi-
tions), afforded solely the ortho-arylated compound 3a in 16
and 12% yields (calculated by GC-MS analysis), respective-
We additionally prepared compounds 3a, 3b, and 3j inde-
pendently to investigate the role of electronic phenomena
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M.-J. Wu et al.
Table 3. Synthesis of 6 and 7 by the reaction of 5 with 2a and PdACTHNUTRGNEUNG(OAc)2
as the catalyst.
Table 3. (Continued)
Entry
5
Product ratio
Yield
[%][b]
6/7[a]
7
trace
Entry
5
Product ratio
Yield
[%][b]
6/7[a]
15:85
[a] The product ratio was calculated by GC-MS analysis (three runs).
[b] The total yield was calculated by GC-MS analysis (three runs).
85
1
10:90
2
3
4
84
94
95
3:97
>1:99
Scheme 1. a) Reaction of 8 and 2a under the optimized reaction condi-
tions reported herein. b) Reaction of 1 and 2a under the conditions re-
ported by Shi and co-workers.[16]
10:90
À
À
on the tandem C H activation/C N formation process in
the synthesis of 4 under optimized reaction conditions
(Scheme 3). The results indicated that electron-donating
À
groups (for example, OMe) could accelerate the palladi-
5
trace
À
À
um(II)-catalyzed, intramolecular C H activation/C N for-
mation process. Consequently, the formation of carbazoles
4a and 4j could be accomplished within 1 h. Reaction times
for the conversion of 3b to 4b, however, were in the order
of six hours due to the impact of the electron-withdrawing
4:96
À
À
group (for example, NO2) on the reaction rate of the C N
bond-formation process. At the same time, we found that
BQ was not essential for this process.
6
trace
Investigation of kinetic isotope effect (kH/kD): To measure
À
the kinetic isotope effect (KIE, kH/kD) of the initial C H ac-
tivation in this catalytic reaction, we prepared a deuterated
substrate, [D]1,[20a] which reacted with 2a (by the one-pot
method under the optimized reaction conditions) to give a
mixture of [D’]3a/3a and [D]4a/4a. The kH/kD values of
>99:1
13616
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Palladium(II)-Catalyzed One-Pot Syntheses of Carbazoles
FULL PAPER
Scheme 3. Synthesis of compounds 4a, 4b, and 4j under the optimized
reaction conditions using starting materials 3a, 3b, and 3j prepared inde-
pendently.
Figure 2. a) Face and b) side views of an ORTEP drawing of N-phenyl-
pyridin-2-amine palladacycle (I). Ellipsoids are shown at the 30% proba-
bility level.[25] Selected bond lengths [ꢁ]: Pd1 Pd2=2.9605(5); Pd1 N1=
À
À
À
À
À
1.994(4); Pd1 C11=1.991(4); Pd1 O1=2.129(3); Pd1 O4=2.114(4);
À
À
À
À
Pd2 N3=1.994(5); Pd2 C26=1.991(5); Pd2 O2=2.126(3); Pd2 O3=
2.086(4). All hydrogen atoms are omitted for clarity.
Scheme 2. Reactions conducted in the presence and absence of BQ to
confirm the importance of this ligand in the catalytic cycle.
both processes were determined as 2.06 and 2.22 (an aver-
age kH/kD of 2.14), respectively (Scheme 4a). In addition,
À
Scheme 4. a) KIE of the first C H activation step by the one-pot
À
the KIE of the first C H bond activation was also measured
À
method. b) KIE of the first C H activation step by the stepwise method.
À
by the stepwise method, as shown in Scheme 4b. Substrate
c) KIE of the second C H activation step.
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M.-J. Wu et al.
[D]1 was treated with a stoichiometric amount of Pd
G
elimination step. PdII is regenerated by the reoxidation of
Pd0 by AgI and BQ and coordinates with the amino group
of 3 to form intermediate 11 with the release of HOAc. Sub-
sequently, intermediate 11 undergoes an aromatic electro-
philic substitution to generate 12 with the release of an ace-
tate anion. Intermediate 12 is rapidly converted into 13
through re-aromatization with the release of a proton. Final-
ly, compound 4 is obtained from 13 with the release of palla-
dium(0), which can again be oxidized to palladium(II) by sil-
ver(I) and BQ, and the regenerated palladium(II) re-enters
the catalytic cycle. Finally, we attempted to synthesize 5-
to form palladacycle [D(H)]I, which was then converted
into [D]4a and 4a. This method gave a kH/kD value of
3.72.[20b] The kH/kD value of the second C H bond activation
À
was calculated as 1.18 by use of the deuterated substrate
[D]3a[20a] (Scheme 4c). The KIE analyses of processes (a)
and (b) shown in Scheme 4 strongly indicate that direct C
À
H cleavage during the first C H activation process is the
À
rate-determining event. Conversely, the second C H activa-
tion process is not rate determining because kH/kD =1.18
(Scheme 4c). Therefore, the second activation process prob-
ably goes through an electrophilic aromatic substitution
pathway.
(pyridin-2-yl)phenanthridin-6ACTHNUGRTNEUNG(5H)-one (14) directly through
the reaction of 1 with 2k. Unfortunately, the yield of prod-
uct 14 was only 28%, probably due to steric hindrance
caused by the ortho substituent (Scheme 6).
Proposed catalytic mechanism: According to the results of
the mechanistic investigations, we propose a plausible mech-
anism for the one-pot synthesis of 4 (Scheme 5). Initially,
PdII is coordinated to the nitrogen atom of the pyridine ring
À
of compound 1 and, subsequently, the ortho C H bond of
the phenyl ring is cleaved by PdII to form I. Aryldifluorobor-
ane 2–BF2 (generated from 2)[3q,21] and I participate in the
transmetalation step to generate intermediate II with con-
comitant release of F2BOAc. Then, BQ coordinates with the
PdII ion of II through a ligand-exchange process to form in-
termediate III.[22] After that, intermediate III is converted
into 3, with the release of Pd0 and BQ, through a reductive
Scheme 6. Synthesis of 14 from 1 and 2k.
Scheme 5. Proposed mechanism for the palladium(II)-catalyzed, one-pot synthesis of 3 and 4 by the reaction of 1 with 2.
13618
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Palladium(II)-Catalyzed One-Pot Syntheses of Carbazoles
FULL PAPER
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[2] For the Stille coupling reaction, see: a) P. Espinet, A. M. Echavar-
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Giralt, Chem. Soc. Rev. 2001, 30, 145–157; e) N. Miyaura, A.
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drichimica Acta 2005, 38, 71–88; g) E. Negishi, Acc. Chem. Res.
1982, 15, 340–348; for the Hiyama coupling reaction, see: h) T.
Hiyama, J. Organomet. Chem. 2002, 653, 58–61; i) K. Takahashi, T.
Minami, Y. Ohara, T. Hiyama, Tetrahedron Lett. 1993, 34, 8263–
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Masse, J. Chem. Soc. Chem. Commun. 1972, 144a; k) K. Tamao, K.
Sumitani, M. Kumada, J. Am. Chem. Soc. 1972, 94, 4374–4376; l) K.
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We have successfully developed a one-pot, palladium(II)-
catalyzed synthesis of 4 directly through the tandem double
À
C H activation/cross-coupling reaction of 1 with 2. The key
intermediate, I, was isolated and the structure was con-
À
firmed by X-ray crystallography. The KIE for both C H ac-
tivation steps was also investigated. This information provid-
ed strong evidence for the proposed mechanism. The report-
ed synthetic methodology provides a convenient path to car-
bazoles, which, in turn, might have potential applications in
the fields of pharmaceutical chemistry and optoelectronics.
Experimental Section
General procedure for the syntheses of 3 and 4: A mixture of 1 (15 mg,
0.088 mmol), 2 (4 equiv), AgOAc (3 equiv), BQ (1 equiv),[23] DMSO
(4 equiv), and PdACHTUNGTRENNUNG(OAc)2 (10 mol%) in 1,4-dioxane (6 mL) was heated to
130–1408C and stirred at this temperature for 48 h. After cooling to
room temperature, the solution was filtered through a pad of Celite and
washed with water (2ꢂ5 mL). The aqueous layers were combined and ex-
tracted with dichloromethane (2ꢂ5 mL). Finally, the organic layers were
combined, dried over MgSO4, filtered, and evaporated under vacuum.
The residue was purified by chromatography on silica gel using n-hexane/
ethyl acetate (30/1 to 10/1) as the eluent to give 3 and 4. All yields were
as follows: 3a: 14% (3.0 mg, 0.012 mmol); 3b: 19% (4.9 mg,
0.017 mmol); 3c: 31% (7.9 mg, 0.027 mmol); 3d: 17% (4.1 mg,
0.015 mmol); 3e: 15% (3.5 mg, 0.013 mmol); 3 f: 25% (6.2 mg,
0.022 mmol); 3g: 24% (6.8 mg, 0.021 mmol); 3h: 13% (3.4 mg,
0.011 mmol); 3i: 18% (4.1 mg, 0.016 mmol); 3j: 13% (3.1 mg,
0.011 mmol); 4a: 66% (14.2 mg, 0.058 mmol); 4b: 58% (14.7 mg,
0.051 mmol); 4c: 48% (12 mg, 0.042 mmol); 4d: 58% (14 mg,
0.051 mmol); 4e: 33% (7.6 mg, 0.029 mmol); 4 f: 45% (11 mg,
0.040 mmol); 4g: 27% (7.6 mg, 0.024 mmol); 4h: 42% (11 mg,
0.037 mmol); 4i: 35% (7.9 mg, 0.031 mmol); 4j: 32% (7.7 mg,
0.028 mmol).
The general procedure for the synthesis of pyridinylamines 6 and carba-
zoles 7 was the same as that of 3 and 4. The amounts of 5 used were as
follows: 5a: 19 mg, 0.088 mmol; 5b: 19 mg, 0.088 mmol; 5c: 18 mg,
0.088 mmol; 5d: 18 mg, 0.088 mmol; 5e: 18 mg, 0.088 mmol; 5 f: 20 mg,
0.088 mmol; 5g: 19 mg, 0.088 mmol. All yields were as follows: 6a: 9%
(2 mg, 0.008 mmol); 6d: 9% (2.2 mg, 0.008 mmol); 7a: 76% (22 mg,
0.067 mmol); 4c: 81% (21 mg, 0.071 mmol); 7c: 94% (23 mg,
0.083 mmol); 4j: 86% (21 mg, 0.076 mmol).
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The procedure for the synthesis of 14 was the same as that of 3 and 4.
All reagents were the same as those used for the synthesis of 3 and 4.
The sole exception was 14, for the synthesis of which 2k (85 mg,
0.35 mmol) was used. The product 14 was obtained in 28% yield (6.7 mg,
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Acknowledgements
We thank the National Science Council of the Republic of China for fi-
nancial support.
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mote transmetalation reductive elimination in literature; see: a) X.
Chen, C. E. Goodhue, J.-Q. Yu, J. Am. Chem. Soc. 2006, 128,
12634–12635; b) X. Chen, J.-J. Li, X.-S. Hao, C. E. Goodhue, J.-Q.
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À
essential ligand for the Suzuki–Miyaura coupling reaction by C H
bond activation, see: a) ref. [3o–q]. In addition, DMSO decelerates
catalyst decomposition and prevents Pd0 aggregation, see: b) K. L.
Hull, M. S. Sanford, J. Am. Chem. Soc. 2007, 129, 11904–11905;
c) K. L. Hull, M. S. Sanford, J. Am. Chem. Soc. 2009, 131, 9651–
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[11] We found that 1 was easy to complex with Cu
desired product 4a was still obtained with good selectivity (3a:4a=
2:98), the product yield was 33%. Additionally, Cu(OAc)2 promoted
ACHTUNGRTEN(NNUG OAc)2. Although the
G
[20] a) For the preparation of deuterated substrates [D]1 and [D]3a, see
the Supporting Information; b) The difference in kH/kD value be-
tween 2.14 (by the one-pot method) and 3.72 (by the stepwise
the self-dimerization of potassium aryltrifluoroborate 2 and led to
the formation of large amounts of the homocoupling product.
À
[12] We found that the product ratio 3a/4a (17:83) was inverted (94:6)
when tert-butanol was used instead of 1,4-dioxane as the solvent. To
verify this observation, we also carried out the reaction of 1 with 2c
and 1 with 2j in tert-butanol to give product ratio values of 92:8 (3c/
4c) and 100:0 (3j/4j) in 80 and 86% yields, respectively. A reasona-
ble explanation for this observation would be that the amine group
of 1 forms a hydrogen bond with the hydroxyl group of the tert-
butyl alcohol and, thus, prevents coordination of the nitrogen atom
method) for the first C H bond activation process might be caused
by different reaction conditions, even so, both of them indicate that
À
the first C H bond activation process indeed occurs as the rate-de-
termining step through direct C H bond cleavage, but not through
the electrophilic substitution pathway.
À
[21] a) G. A. Molander, L. N. Cavalcanti, B. Canturk, P.-S. Pan, L. E.
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[22] An analogous transmetalation process from intermediate I to III
was also proposed by Sanford and co-workers, see ref. [10c].
[23] Fresh BQ obtained through sublimation was used.
[24] CCDC-823006 (3j) and 823007 (4a) contain the supplementary crys-
tallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
À
of the amine with palladium(II). Therefore, the second C H bond
À
activation/C N bond formation process could not take place to gen-
erate carbazoles 4.
[13] a) Five different amounts (1, 2, 3, 4, and 5 equiv) of 2a and b) four
different amounts (1, 2, 3, and 4 equiv) of AgOAc were screened for
the catalytic reaction. The total yield of products 3a and 4a was 39,
47, 74, 80, and 79% for case (a) and 54, 59, 80, and 78% for case
(b).
[14] For pyridine·Ag+ complexes, see: a) Y. O. Jang, S. W. Lee, Poly-
hedron 2010, 29, 2731–2738; b) Z.-P. Deng, L.-N. Zhu, S. Gao, L.-H.
Huo, S. W. Ng, Cryst. Growth Des. 2008, 8, 3277–3284.
[15] S. Yang, B. Li, X. Wan, Z. Shi, J. Am. Chem. Soc. 2007, 129, 6066–
6067.
[25] CCDC-823005 (I) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[16] Z. Shi, B. Li, X. Wan, J. Cheng, Z. Fang, B. Cao, C. Qin, Y. Wang,
Angew. Chem. 2007, 119, 5650–5654; Angew. Chem. Int. Ed. 2007,
46, 5554–5558.
Received: May 18, 2011
Published online: October 24, 2011
13620
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Chem. Eur. J. 2011, 17, 13613 – 13620