Nickel-Catalyzed N-Arylation Using N -Trimethylsilyl-carbazole

Article abstract of DOI:10.1055/s-0036-1588417

Nickel-catalyzed N-arylation reaction of N -trimethylsilyl-carbazole using aryl bromides is found to proceed in the presence of sodium acetate, giving N -aryl-carbazoles in high yields. Under these conditions, N -trimethylsilyl-carbazole could react with aryl bromides selectively even in the presence of other N -trimethylsilyl-amines or N -H-amines. This arylation reaction was applied to the polymerization to provide a polycarbazole.

Full text of DOI:10.1055/s-0036-1588417

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© Georg Thieme Verlag Stuttgart · New York
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Y. Minami et al.
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Nickel-Catalyzed N-Arylation Using N-Trimethylsilyl-carbazole
Yasunori Minami*a
R2
R2
Takeshi Komiyamab
Kenta Shimizub
Shu-ichi Unob
Ni cat.
R1
N
R1
+
Br
TMS
N
Tamejiro Hiyama*a
Osamu Gotoc
R2
R2
Hideyuki Ikehirad
R1 = H, OMe, NPh2
CF3, NO2 etc.
R2 = H, Cl
·
·
·
11 examples
39–99% yield
selective formation
a Research and Development Initiative, Chuo University, Kasuga,
Bunkyo-ku, Tokyo 112-8551, Japan
in the presence of diarylamines
yminami@kc.chuo-u.ac.jp
thiyama@kc.chuo-u.ac.jp
b Faculty of Science and Engineering, Chuo University, Kasuga,
Bunkyo-ku, Tokyo 112-8551 Japan
c Sumitomo Chemical, 3-1-98 Kasugadenaka, Konohana-ku,
Osaka, 554-8558, Japan
d Sumika Technical Information Service, 4-6-17 Koraibashi,
Chuo-ku, Osaka, 541-0043, Japan
Published as part of the Cluster Silicon in Synthesis and Catalysis
Received: 06.03.2017
Accepted after revision: 11.04.2017
Published online: 08.05.2017
enough to achieve the N-arylation of N-TMS-carbazole al-
though various aryl bromides can cross-couple with N-
TMS-dialkyl, alkyl-aryl, and diarylamines in excellent
yields. Thus, we decided to optimize conditions for the sili-
con-based N-arylation of carbazoles. Herein reported is the
nickel-catalyzed silicon-based C–N coupling particularly
suitable to the synthesis of N-aryl carbazoles.8 The nickel-
based new protocol exhibits selective formation of N-aryl-
carbazoles even in the presence of other N-H or N-TMS
amines, realizing easy construction of carbazole-based or-
ganic materials.9
DOI: 10.1055/s-0036-1588417; Art ID: st-2017-b0163-c
Abstract Nickel-catalyzed N-arylation reaction of N-trimethylsilyl-car-
bazole using aryl bromides is found to proceed in the presence of sodi-
um acetate, giving N-aryl-carbazoles in high yields. Under these condi-
tions, N-trimethylsilyl-carbazole could react with aryl bromides
selectively even in the presence of other N-trimethylsilyl-amines or N-
H-amines. This arylation reaction was applied to the polymerization to
provide a polycarbazole.
Key words carbazole, C–N bond formation, nickel, polymerization
Pd(dba)2 (2 mol%)
Xphos (4 mol%)
Introduction of an aryl group on nitrogen of carbazole
and its derivatives is an important transformation for the
construction of such as organic materials1 mainly owing to
an effective electron-donating character of the carbazole
unit.2 For effective design of such materials, a reliable syn-
thetic method for N-arylcarbazoles is needed.
R
Br
N
N
TMS
R
+
KF (5 equiv)
DMI, 100 °C, 24 h
1a (R = CF3)
1b (R = Me)
2a (1.1 equiv)
3a (R = CF3), 99%
3b (R = Me), <5%
Scheme 1 Palladium-catalyzed cross-coupling of aryl bromides with
N-TMS-carbazole; DMI = 1,3-dimethyl-2-imidazolidinone
For C–N bond formation, the palladium-catalyzed cross-
coupling is straightforward. Recently, we disclosed that the
silicon-based C–N bond-forming reaction of aryl bromides
with N-TMS-amines using palladium catalysts3–5 proceeds
effectively with unique selectivity different from the
Buchwald–Hartwig and Ullmann reactions.6,7 For example,
p-trifluoromethylbromobenzene (1a) couples with N-TMS-
carbazole (2a) smoothly to give N-aryl-carbazole 3a in
quantitative yield, as shown in Scheme 1. However, the pal-
ladium-catalyzed N-arylation of carbazole is not applicable
to slightly electron-rich p-bromotoluene (1b). This result
suggests that the palladium singular catalyst is not potent
We first examined the reaction of 1b with 2a in the
presence of various nickel catalysts, ligands, and bases and
found that the catalytic conditions consisting of Ni(cod)2 (5
mol%)/IPr [N,N′-bis-[2,6-(diisopropyl)phenyl]imidazol-2-
ylidene]/NaOAc in CPME at 100 °C gave N-(p-tolyl)-carba-
zole 3b in 85% yield after 24 hours (Table 1, entry 1). Exam-
ination of other solvents such as 1,4-dioxane, diisopropyl-
ether, toluene, DMF, and DMI decreased the yield of 3b. Af-
ter other bulky ligands (Figure 1) were tested under these
conditions, the combination of SIPr [1,3-bis(2,6-diisopro-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

B
Y. Minami et al.
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pylphenyl)imidazolinium chloride]·HCl and KOt-Bu, which
is a reductant for SIPr·HCl, afforded 3b in 93% yield (Table 1,
entries 2–9). Finally, 10 mol% of catalysts Ni(cod)2/SIPr·HCl/
KOt-Bu produced 3b in best yield (Table 1, entry 10). Other
bases such as m2CO3 (m = Li, Na, K, and Cs), KOAc, K3PO4,
and KOt-Bu decreased the reactivity. Of note, CsF as an ef-
fective base for palladium-catalytic conditions afforded no
coupling product.
group OMe (1c), NMe2 (1d), and NPh2 (1e) smoothly react-
ed to give the corresponding products in good yields (Table
2, entries 2–4). Unsubstituted bromobenzene (1f) also gave
a coupling product 3f in a high yield (Table 2, entry 5). 4-
Nitrobromobenzene (1g) gave the coupled product 3g in a
low yield (Table 2, entry 6), clearly suggesting that an elec-
tron-withdrawing group retards the nickel-catalyzed C–N
coupling in contrast to the palladium-catalyzed coupling.
Table 2 Scope of the Reactiona
Table 1 Nickel-Catalyzed Cross-Coupling of p-Bromotoluene (1b) with
2aa
Ni(cod)2 (10 mol%)
SIPr·HCl (10 mol%)
KOt-Bu (10 mol%)
Ni(cod)2 (5 mol%)
ligand (5 mol%)
Ar Br
+
TMS
N
Ar
N
NaOAc (1.7 equiv)
CPME, 100 °C
Me
Br
TMS
N
Me
N
+
NaOAc (1.7 equiv)
CPME (1 M)
100 °C, 24 h
2 (1.3 equiv)
3
1
1b
2a (1.3 equiv)
3b
Entry
1
2
Time (h) Product
Yield (%)b
Entry
Ligand (mol%)
IPr (5)
Yield of 3b (%)b
1
2
90
R
N
SIPr·HCl/KOt-Bu (5)
IMes·HCl/KOt-Bu (5)
SIMes·HCl/KOt-Bu (5)
XPhos (5)
93
3
83
4
66
1
2
3
4
5
6
1a
2a
12
18
24
18
18
72
3a R = CF3
3c R = OMe
3d R = NMe2
3e R = NPh2
3f R = H
83
90
77
99
88
39
5
84
1c
1d
1e
1f
2a
2a
2a
2a
2a
6
PCy3 (10)
30
7
Pt-Bu3 (10)
trace
19
8
DPPFc (5)
9
Xantphosd (5)
SIPr·HCl/KOt-Bu (10)
12
1g
3g R = NO2
10c
96e
a Unless otherwise noted, a mixture of 1b (0.50 mmol), 2a (0.65 mmol),
Ni(cod)2 (25 μmol), ligand (25 μmol), NaOAc (0.85 mmol), and CPME (0.50
mL) were heated at 100 °C for 24 h; CPME = cyclopentyl methyl ether.
b Determined by NMR spectroscopy.
N
7
8
1h
2a
2a
24
36
90
67
c DPPF = 1,1′-bis(diphenylphosphino)ferrocene.
d Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene.
e Isolated yield.
3h
N
1i
S
N
N
N
N
Ar
Ar
Ar
Ar
IPr (Ar = 2,6-(iPr)2C6H3)
IMes (Ar = 2,4,6-(Me)3C6H2)
SIPr (Ar = 2,6-(iPr)2C6H3)
SIMes (Ar = 2,4,6-(Me)3C6H2)
3i
Cl
Cy2P iPr
iPr
MeO
N
9
1c
1c
2b
2c
24
36
78
67
iPr
XPhos
Cl
Figure 1 Various ligands
3j
Ph
Ph
MeO
N
10c
Various bromoarenes were applied to the reaction with
2a, and the results are summarized in Table 2.10 In this nick-
el-catalyzed C–N coupling, 4-trifluoromethylbromoben-
zene (1a) also gave coupled product 3a in 83% yield as is the
case for palladium-catalytic conditions (Table 2, entry 1).
Moreover, bromobenzenes with an electron-donating
3k
a Unless otherwise noted, a mixture of 1 (0.50 mmol), 2 (0.65 mmol),
Ni(cod)2 (50 μmol), SIPr·HCl (50 μmol), KOt-Bu (50 μmol), NaOAc (0.85
mmol), and CPME (0.50 mL) were heated at 100 °C.
b Isolated yield.
c CsF was used instead of NaOAc.
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Y. Minami et al.
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This means selection of palladium or nickel catalyst al-
lows the synthesis of whole range of electron-demanded N-
arylcarbazoles. 2-Bromonaphthalene gave N-(2-naphth-
yl)carbazole (3h) in 90% yield (Table 2, entry 7). When 3-
bromothiophene was applied, the desired thienyl carbazole
(3i) was obtained in a moderate yield (Table 2, entry 8). 3,6-
Dichloro-N-TMS-carbazole (2b) underwent the arylation
without a loss of chlorines to give 3j in 78% yield (Table 2,
entry 9). Instead of N-TMS-carbazoles, N-TMS-diphenyl-
amine (2c) was also applied to the nickel-catalysis condi-
tions using CsF as a base to form triarylamine 3k in 67%
yield (Table 2, entry 10). Of note, N-H-carbazole (4a) and
3,6-dichloro-N-H-carbazole (4b) barely reacted with 1c un-
der these conditions, which clearly demonstrated that the
TMS group on nitrogen is crucial for this coupling.
ence of nickel catalysts, other N-H-amines or N-TMS-
amines remaining unreacted. Thus, the present nickel-cata-
lyzed reaction is particularly effective for the synthesis of
N-arylcarbazoles selectively even in the presence of reac-
tive secondary amines.
Ph
Ph
Ph
Ph
conditions
24 h
H
N
PMP
N
+
PMP
N
+
2a
1c
+
(1.1 equiv)
4c (1.1 equiv)
conditions
3c
3k
A (Pd cat.)
B (Ni cat.)
0%
0%
0%
85%
Scheme 3 Competition experiment between 2a and 4a under the re-
action of 1c; both conditions A and B are same as in Scheme 2
The scope of the reaction shows that this C–N coupling
is useful for selective N-arylation of carbazoles even in the
presence of other amino functional groups as shown below.
Competition reaction between N-TMS-carbazole 2a and
other N-TMS-amines under the optimized conditions of
palladium- and nickel-catalyzed ones (Scheme 2). Under
conditions A (Pd(dba)2/Xphos/CsF) a mixture of electron-
deficient or -rich bromoarene (1c or 1a), 2a, and 2c failed to
give coupled product in DMI at 100 °C, whereas under con-
On the other hand, competition reaction using 2a and a
N-H-3,6-dichlorocarbazole (4b) was carried out and ob-
tained N-aryl-3,6-dichlorocarbazole 3j as a major product
(Scheme 4). This result suggests that more electron-defi-
cient 4b should be activated by a species from the reaction
of 2a with NaOAc. In fact, a competition reaction using nor-
mal carbazole (4a) and 2b gave 3j selectively (Scheme 4).
Cl
Cl
ditions
B (Ni(cod)2/SIPr·HCl/KOt-Bu/NaOAc) both bro-
Ni(cod)2 (5 mol%)
SIPr·HCl (5 mol%)
KOt-Bu (5 mol%)
moarenes reacted with 2a selectively to give N-arylcarba-
zoles 3a and 3c in excellent yields. This reactivity difference
was also observed in the case of N-TMS-morpholine.
H
N
PMP
N
PMP
N
+
NaOAc (1.7 equiv)
CPME
100 °C, 24 h
Cl
Cl
Ph
4b (1.1 equiv)
3c, 5%
3j, 39%
TMS
N
+
Ph
1c
2a
2c (1.1 equiv)
(1.1 equiv)
+
1a
or
1c
+
2a
Ph
Ph
conditions
24 h
Ni(cod)2 (5 mol%)
SIPr·HCl (5 mol%)
KOt-Bu (5 mol%)
R
N
R
N
+
H
N
+
3c, 11%
3j, 74%
NaOAc (1.7 equiv)
CPME
(1.1 equiv)
3a (R = CF3)
3l (R = CF3)
conditions
A (Pd cat.)
B (Ni cat.)
100 °C, 24 h
5%
99%
0%
0%
4a (1.1 equiv)
+
3c (R = OMe)
3k (R = OMe)
1c
2b
(1.1 equiv)
0%
91%
A
B
0%
0%
Scheme 4 Competition experiment between N-H-carbazoles and their
N-TMS-forms
Scheme 2 Competition experiments between 2a and 2c under the re-
action of 1. Conditions A: Pd(dba)2 (1 mol%), Xphos (2 mol%), and CsF
(1.5 equiv) in DMI (1 M) at 100 °C for 24 h. Conditions B: Ni(cod)2 (5
mol%), SIPr·HCl (5 mol%), KOt-Bu (5 mol%), and NaOAc (1.7 equiv) in
CPME (1 M) at 100 °C for 24 h.
Finally, the nickel-catalyzed reaction was applied to
cross-coupling polymerization. N-TMS-3-bromo-6-octyl-
carbazole (5) was allowed to react under the optimized
conditions to afford C–N-coupled polycarbazole 6 with Mw
8800 and PDI 1.7 in 90% yield (Scheme 5). When the load-
ing of nickel catalyst was reduced to 5 mol%, slightly yield of
6 was slightly decreased to 70% with Mw 8000 and PDI 1.8.
This type of oligocarbazole was prepared in a stepwise
manner by Lu and co-workers.11 In contrast, the present re-
action is straightforward and useful for the synthesis of
polycarbazoles.12
We next examined the competition experiments be-
tween 2a and diphenylamine (4c) under the same condi-
tions (Scheme 3). Diphenylamine (4c) totally failed to react
with 1c by palladium catalysis (conditions A), whereas the
present nickel-catalysis induced selective N-arylation of
carbazole (2a) (conditions B). These results suggest that
NaOAc as a base can only activate N-TMS-carbazole and its
derivatives to cross-couple with bromoarenes in the pres-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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Y. Minami et al.
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(e) Ishimatsu, R.; Matsunami, S.; Kasahara, T.; Mizuno, J.; Edura,
T.; Adachi, C.; Nakano, K.; Imato, T. Angew. Chem. Int. Ed. 2014,
53, 6993.
TMS
N
Ni(cod)2 (10 mol%)
SIPr·HCl (10 mol%)
KOt-Bu (10 mol%)
Br
N
n
(3) (a) Shimizu, K.; Minami, Y.; Goto, O.; Ikehira, H.; Hiyama, T.
Chem. Lett. 2014, 43, 438. (b) Minami, Y.; Komiyama, T.;
Shimizu, K.; Hiyama, T.; Goto, O.; Ikehira, H. Bull. Chem. Soc. Jpn.
2015, 88, 1437.
NaOAc (1.7 equiv)
CPME, 100 °C, 2 d
Oct
Oct
6, 90%, Mn = 5200, Mw = 8800
w/Mn = 1.7
5
M
(4) (a) Barluenga, J.; Aznar, F.; Valdés, C. Angew. Chem. Int. Ed. 2004,
43, 343. (b) Smith, C. J.; Early, T. R.; Holmes, A. B.; Shute, R. E.
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Holmes, A. B.; Danheiser, R. L.; Tester, J. W. Org. Biomol. Chem.
2005, 3, 3767.
(5) For recent reviews of cross-coupling reaction using organosi-
lanes, see: (a) Sore, H. F.; Galloway, W. R. J. D.; Spring, D. R.
Chem. Soc. Rev. 2012, 41, 1845. (b) Denmark, S. E.; Ambrosi, A.
Org. Process Res. Dev. 2015, 19, 982. (c) Komiyama, T.; Minami,
Y.; Hiyama, T. ACS Catal. 2017, 7, 631.
Scheme 5 Palladium-catalyzed cross-coupling polymerization of 3-
bromo-N-TMS-carbazole (5)
In conclusion, we have disclosed that the nickel(0)-cata-
lyzed C–N bond-forming cross-coupling of aryl halides with
N-trimethylsilyl-carbazoles proceeds smoothly to form N-
aryl-carbazoles. The feature of the present C–N coupling is
attributed to a selective activation of N-trimethylsilyl-car-
bazoles by sodium acetate. In addition, this arylation proto-
col proceeds selectively even in the presence of other N-
trimethylsilyl-amines and N-H-secondary amines including
free carbazole. Moreover, this protocol is applicable to
cross-coupling polymerization of N-trimethylsilyl-bromo-
carbazole.
(6) Hooper, M. W.; Utsunomiya, M.; Hartwig, J. F. J. Org. Chem.
2003, 68, 2861.
(7) For reviews, see: (a) Ley, S. V.; Thomas, A. W. Angew. Chem. Int.
Ed. 2003, 42, 5400. (b) Evano, G.; Blanchard, N.; Toumi, M. Chem.
Rev. 2008, 108, 3054. (c) Hartwig, J. F. Acc. Chem. Res. 2008, 41,
1534. (d) Surry, D. S.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008,
47, 6338. (e) Monnier, F.; Taillefer, M. Angew. Chem. Int. Ed.
2009, 48, 6954. (f) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2010, 1,
13. (g) Sadig, J. E. R.; Willis, M. C. Synthesis 2011, 1. (h) Surry, D.
S.; Buchwald, S. L. Chem. Sci. 2011, 2, 27. (i) Beletskaya, I. P.;
Cheprakov, A. V. Organometallics 2012, 31, 7753. (j) Rauws, T. R.
M.; Maes, B. U. W. Chem. Soc. Rev. 2012, 41, 2463. (k) R.-Castillo,
P.; Buchwald, S. L. Chem. Rev. 2016, 116, 12564.
Funding Information
Grants-in-Aid for Young Scientists (B) 25870747
Japan Science and Technology Agency ACT-C
(8) Hiyama, T.; Minami, Y.; Ikehira, H.; Goto, O. JP 2014196464
2014; brief working examples including polymerization are
listed in the patent
Supporting Information
(9) For reviews of Ni-catalyzed C–N bond-forming coupling, see:
(a) Schranck, J.; Rotzler, J. Org. Process Res. Dev. 2015, 19, 1936.
(b) Marín, M.; Rama, R. J.; Nicasio, M. C. Chem. Rec. 2016, 16,
1819.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588417.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(10) General Experimental Procedure for the Synthesis of N-Aryl-
carbazoles
References and Notes
A mixture of Ni(cod)2 (0.050 mmol), SIPr·HCl (0.050 mmol),
KOt-Bu (0.050 mmol), and CPME was stirred at 100 °C for 30
min. To this was added NaOAc (0.85 mmol), aryl bromide 1
(0.50 mmol), and N-TMS-carbazole 2 (0.65 mmol). The reaction
mixture was quenched with H2O. The aqueous layer was
extracted with Et2O and washed with brine. The combined
organic layers were dried over anhydrous MgSO4. After concen-
tration in vacuo, the residue was purified by flash chromatogra-
phy on silica gel or preparative TLC to afford N-aryl-carbazoles 3.
(1) For recent selected examples, see: (a) Suzuki, K.; Hori, Y.;
Kobayashi, T. Adv. Synth. Catal. 2008, 350, 652. (b) Zhu, R.; Xing,
L.; Wang, X.; Cheng, C.; Su, D.; Hu, Y. Adv. Synth. Catal. 2008,
350, 1253. (c) Kwon, J. K.; Cho, J. H.; Ryu, Y.-S.; Oh, S. H.; Yum, E.
K. Tetrahedron 2011, 67, 4820. (d) Guo, F.; Wang, L.; Wang, P.;
Yu, J.; Han, J. Asian J. Org. Chem. 2012, 1, 218. (e) Creutz, S. E.;
Lotito, K. J.; Fu, G. C.; Peters, J. C. Science 2012, 338, 647.
(f) Louillat, M.-L.; Patureau, F. W. Org. Lett. 2013, 15, 164.
(g) Ziegler, D. T.; Choi, J.; Muñoz-Molina, J. M.; Bissember, A. C.;
Peters, J. C.; Fu, G. C. J. Am. Chem. Soc. 2013, 135, 13107.
(h) Crawford, S. M.; Lavery, C. B.; Stradiotto, M. Chem. Eur. J.
2013, 19, 16760. (i) Nakayama, Y.; Yokoyama, N.; Nara, H.;
Kobayashi, T.; Fujiwhara, M. Adv. Synth. Catal. 2015, 357, 2322.
(j) Yoo, W.-J.; Tsukamoto, T.; Kobayashi, S. Org. Lett. 2015, 17,
3640. (k) Chen, F.; Liu, N.; Ji, E.; Dai, B. RSC Adv. 2015, 5, 51512.
(2) For selected examples, see: (a) Jiang, W.; Duan, L.; Qiao, J.; Dong,
G.; Zhang, D.; Wang, L.; Qiu, Y. J. Mater. Chem. 2011, 21, 4918.
(b) Uoyama, H.; Goushi, K.; Shizu, K.; Nomura, H.; Adachi, C.
Nature (London, U.K.) 2012, 492, 234. (c) Chen, Q.; Luo, M.;
Hammaeshøj, P.; Zhou, D.; Han, Y.; Laursen, B. W.; Yan, C.-G.;
Han, B.-H. J. Am. Chem. Soc. 2012, 134, 6084. (d) Komino, T.;
Tanaka, H.; Adachi, C. Chem. Mater. 2014, 26, 3665.
N-(4-Methoxyphenyl)-3,6-dichloro-9H-carbazole
(3j)
was
obtained according to the general experimental procedure. Pale
yellow solid; yield 140 mg (78%). 1H NMR (400 MHz, CDCl3): δ =
3.90 (s, 3 H), 7.08 (d, J = 9.2 Hz, 2 H), 7.19 (d, J = 8.8 Hz, 2 H),
7.32–7.35 (m, 4 H), 8.00 (d, J = 2.0 Hz, 2 H). 13C NMR (126 MHz,
CDCl3): δ = 55.7, 111.1, 115.4, 120.2, 123.3, 125.6, 126.8, 128.5,
129.5, 140.2, 159.4. MS (EI, 70 eV): m/z (%) = 341 (100) [M+], 326
(33), 306 (3), 262 (16), 228 (14), 171 (4).
(11) Xu, T.; Lu, R.; Jin, M.; Qui, X.; Xue, P.; Bao, C.; Zhao, Y. Tetrahe-
dron Lett. 2005, 46, 6883.
(12) The Supporting Information can be used for detailed procedures
and the characterization data of other products.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D