Synthesis of N-vinylcarbazoles via dehydrogenative coupling of N-H carbazoles with alkenes under palladium catalysis

Article abstract of DOI:10.1021/ol4001697

The synthesis of N-vinylcarbazoles was achieved by the palladium-catalyzed aza-Wacker reaction of N-H carbazoles with styrenes. In this reaction, Markovnikov adducts were exclusively produced. In contrast, the reaction with electron-deficient alkenes such

Full text of DOI:10.1021/ol4001697

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Synthesis of N‑Vinylcarbazoles via
Dehydrogenative Coupling of N‑H
Carbazoles with Alkenes under
Palladium Catalysis
Daisuke Takeda,† Koji Hirano,† Tetsuya Satoh,*,†,‡ and Masahiro Miura*,†
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita,
Osaka 565-0871, Japan, and JST, ACT-C, 4-1-8 Honcho, Kawaguchi,
Saitama 332-0012, Japan
satoh@chem.eng.osaka-u.ac.jp; miura@chem.eng.osaka-u.ac.jp
Received January 20, 2013
ABSTRACT
The synthesis of N-vinylcarbazoles was achieved by the palladium-catalyzed aza-Wacker reaction of N-H carbazoles with styrenes. In this
reaction, Markovnikov adducts were exclusively produced. In contrast, the reaction with electron-deficient alkenes such as acrylates and
acrylamides gave only anti-Markovnikov adducts.
N-Vinylcarbazoles have been recognized to be an
important class of monomers for the production of poly-
(vinylcarbazole)s.1 Polymers and oligomers containing
carbazole moieties are now widely utilized in organic
electroluminescence (EL) devices, photocopiers, and non-
linear optical (NLO) systems, etc.1,2 However, their con-
ventional preparation methods are problematic because
of their multistep procedures and low selectivity and
efficiency. Recently, the palladium- and copper-catalyzed
coupling reactions of N-H carbazoles with vinyl bromides
have been developed for the simple preparation of
N-vinylcarbazoles.3 From the atom- and step-economical
points of view, a more attractive approach is the oxidative
coupling of N-H carbazoles with alkenes. In this kind of
intermolecular aza-Wacker reaction, however, the nucleo-
philes are so far limited to amides and carbamates.4
(3) (a) Liao, Q.; Wang, Y.; Zhang, L.; Xi, C. J. Org. Chem. 2009, 74,
6371. (b) Dehli, J. R.; Legros, J.; Bolm, C. Chem. Commun. 2005, 973.
(c) Lebedev, A. Y.; Izmer, V. V.; Kazyul’kin, D. N.; Beletskaya, I. P.;
Voskoboynikov, A. Z. Org. Lett. 2002, 4, 623. See also reviews concern-
ing catalytic CÀN coupling reactions of organic halides with amines:
(d) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem.
Res. 1998, 31, 805. (e) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852.
(4) (a) Liu, X.; Hii, K. K. Eur. J. Org. Chem. 2010, 5181. (b) Liu, G.;
Stahl, S. S. J. Am. Chem. Soc. 2007, 129, 6328. (c) Lee, J. M.; Ahn, D.- S.;
Jung, D. Y.; Lee, J.; Do, Y.; Kim, S. K.; Chang, S. J. Am. Chem. Soc.
2006, 128, 12954. (d) Timokhin, V. I.; Stahl, S. S. J. Am. Chem. Soc.
2005, 127, 17888. (e) Brice, J. L.; Harang, J. E.; Timokhin, V. I.;
Anastasi, N. R.; Stahl, S. S. J. Am. Chem. Soc. 2005, 127, 2868. (f)
Timokhin, V. I.; Anastasi, N. R.; Stahl, S. S. J. Am. Chem. Soc. 2003,
125, 12996. (g) Hosokawa, T.; Takano, M.; Kuroki, Y.; Murahashi, S.-I.
Tetrahedron Lett. 1992, 33, 6643. See also a review: (h) Kotov, V.;
Scarborough, C. C.; Stahl, S. S. Inorg. Chem. 2007, 46, 1910.
† Osaka University.
‡ JST.
(1) Selected examples: (a) Yomogida, T.; Watanabe, M.; Takeshima,
M.; Aoki, S. Jpn. Kokai Tokkyo Koho. JP 201241387, 2012. (b) Angiuli,
M.; Ciardelli, F.; Colligiani, A.; Greco, F.; Romano, A.; Ruggeri, G.;
Tombari, E. Appl. Opt. 2006, 45, 7928. (c) Brustolin, F.; Castelvetro,
V.; Ciardelli, F.; Rugger, G.; Colligiani, A. J. Polym. Sci., Part A:
Polym. Chem. 2001, 39, 253. (d) Park, S.-H.; Ogino, K.; Sato, H. Synth.
Met. 2000, 113, 135. (e) Trofimov, B. A.; Mikhaleva, A. I.; Morozova,
L. V. Russ. Chem. Rev. 1985, 54, 609.
(2) Selected examples: (a) Jiang, W.; Duan, L.; Qiao, J.; Dong, G.;
Zhang, D.; Wang, L.; Qui, Y. J. Mater. Chem. 2011, 21, 4918. (b)
Albrecht, K.; Yamamoto, K. J. Am. Chem. Soc. 2009, 131, 2244. (c)
Watanabe, S.; Okada, H. Jpn. Kokai Tokkyo Koho. JP 200418787,
2004. (d) Kawakami, T.; Sonoda, N. Appl. Phys. Lett. 1993, 62, 2167.
r
10.1021/ol4001697
XXXX American Chemical Society

Table 1. Reaction of Carbazole (1a) with Styrene (2a)a
Table 2. Reaction of Carbazoles 1 with Styrenes 2a
entry
oxidant (mmol)
solvent
yield of 3ab (%)
1
AgOAc (0.4)
AgOAc (0.4)
AgOAc (0.4)
AgOAc (0.4)
AgOAc (0.4)
AgOAc (0.4)
Ag2CO3 (0.2)
MeCN
o-xylene
dioxane
diglyme
DME
84
49
2
3
54
4
39
5
48
6
DMF
58
7c
8
MeCN
MeCN
MeCN
MeCN
>99 (85)
53
Cu(OAc)2 H2O (0.4)
3
9d
10e
Cu(OAc)2 H2O (0.04)
57
3
Cu(OAc)2 H2O (0.04)
39
3
a Reaction conditions: [1a]/[2a]/[Pd(OAc)2] = 0.2:1:0.02 (in mmol),
in solvent (2 mL) at 100 °C for 6 h under N2, unlessotherwise noted. b GC
yield based on the amount of 1a used. Value in parentheses indicates
yield after purification. c For 3 h. d Under O2. e Under air.
Although one exception using anilines has been known,5
there is, to our knowledge, no report of the reactions of
azoles.6 In the context of our studies of the palladium-
catalyzed oxidative coupling of nitrogen-containing
heteroarenes,7 we succeeded in finding that the novel
aza-Wacker-type dehydrogenative coupling of carbazoles
with alkenes can be realized under palladium catalysis
to produce N-vinylated carbazole derivatives.8 Depending
on the identities of alkenes, Markovnikov- or anti-
Markovnikov adducts can be exclusively obtained. These
new findings are described herein.
In an initial attempt, carbazole (1a) (0.2 mmol) was
treated with an excess amount of styrene (2a) (1 mmol) in
the presence of Pd(OAc)2 (0.02 mmol) and AgOAc
(0.4 mmol) as catalyst and oxidant, respectively, in MeCN
(2 mL) at 100 °C for 6 h under N2. As a result, the
dehydrogenative coupling effectively proceeded to afford
a Markovnikov adduct, 9-(1-phenylethenyl)-9H-carbazole
(3a) in84% yield, along witha small amount(ca. 5%) ofan
isomer (entry 1 in Table 1). The reaction was somewhat
sluggish in other solvents such as o-xylene, dioxane,
diglyme, DME, and DMF (entries 2À6). Interestingly,
the use of Ag2CO3 (0.2 mmol) in place of AgOAc
a Reaction conditions: [1]/[2]/[Pd(OAc)2]/[Ag2CO3] = 0.2:1:0.02:0.2
(in mmol), in MeCN (2 mL) at 100 °C for 3 h under N2, unless otherwise
noted. b GC yield based on the amount of 1 used. Value in parentheses
indicates yield after purification. c For 1 d. d At 120 °C.
promoted effectively to produce 3a quantitatively within
3 h (entry 7). The reaction also proceeded even under
O2 atmosphere in the presence of a catalytic amount of
(5) Bozell, J. J.; Hegedus, L. S. J. Org. Chem. 1981, 46, 2561.
(6) Baran and co-workers recently reported the palladium-catalyzed
N-tert-prenylation of indoles: Luzung, M. R.; Lewis, C. A.; Baran, P. S.
Angew. Chem., Int. Ed. 2009, 48, 7025.
Cu(OAc)2 H2O (0.04 mmol) to give 3a in a moderate yield
(entry 9). Under air, however, the product yield was
reduced further (entry 10).
3
(7) (a) Miyasaka, M.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem.
2010, 75, 5421. (b) Yamashita, M.; Horiguchi, H.; Hirano, K.; Satoh, T.;
Miura, M. J. Org. Chem. 2009, 74, 7481. (c) Yamashita, M.; Hirano, K.;
Satoh, T.; Miura, M. Org. Lett. 2009, 11, 2337. (d) Maehara, A.;
Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008, 10, 1159.
(8) During the preparation of this manuscript, Jiang, Wang, and co-
workers reported the palladium-catalyzed oxidative coupling of azoles
with alkynes: (a) Wang, L.; Huang, J.; Peng, S.; Liu, H.; Jiang, X.; Wang,
J. Angew. Chem., Int. Ed. 2013, 52, 1768. For a related reaction of carbon
nucleophiles with alkynes, see: (b) Wang, L.; Peng, S.; Wang, J. Chem.
Commun. 2011, 47, 5422.
The reactions of various carbazoles 1 with styrenes 2
were next examined. Under optimized conditions in
Table 1 (entry 7), a series of para-substituted styrenes
2bÀd underwent coupling with 1a to afford the corres-
ponding 9-[1-(p-substituted phenyl)ethenyl]-9H-carbazoles
3bÀd in good yields (entries 1À3 in Table 2). 2-Vinylna-
phthalene (2e) could also be employed in place of styrenes
B
Org. Lett., Vol. XX, No. XX, XXXX

(entry 4). Under similar conditions, 3,6-di-tert-butylcarbazole
(1b) reacted efficiently with 2a to form an aza-Wacker
product 3f (entry 5). In contrast, the reactions of relatively
electron-poorer carbazoles such as 3,6-dichloro- and
3,6-dibromocarbazoles 1c and 1d were sluggish. After
1 d, the corresponding products 3g and 3h were obtained
in 79 and 69% yields, respectively (entries 6 and 7).
Especially in the latter case, heating at 120 °C was required.
3-Monobromocarbazole (1e) also underwent the reaction,
albeit with moderate efficiency (entry 8).
Scheme 2
A plausible mechanism for the reaction of carbazole (1a)
with styrene 2 is illustrated in Scheme 1, in which neutral
ligands are omitted. Coordination of 2 to a PdII center and
subsequent nucleophilic attack on the resulting inter-
mediate A by 1 take place to form an alkylpalladium
intermediate B, accompanied by CÀN bond formation.
Finally, β-hydrogen elimination may occur to release 3.
The PdII species seems to be regenerated by AgI. Similar
Markovnikovregioselectivityhas alsobeenobserved inthe
palladium-catalyzed aza-Wacker reaction of styrenes with
amides.4d,f
Table 3. Reaction of Carbazole 1a with Acrylates or
Acrylamides 5a
Scheme 1
temp
entry
5
(°C) time
6, yieldb (%)
1
5a: R = CO2nBu
5a: R = CO2nBu
100
100
100
80
6 h 6a: R = CO2nBu, 63
6 h 6a: R = CO2nBu, 25
6 h 6a: R = CO2nBu, 22
6 h 6a: R = CO2nBu, 72
6 h 6a: R = CO2nBu, 48
2c
3d,e 5a: R = CO2nBu
4
5a: R = CO2nBu
5a: R = CO2nBu
5a: R = CO2nBu
5a: R = CO2nBu
5
60
6
60 1.5 d 6a: R = CO2nBu, 90 (85)
7
rt
8 d 6a: R = CO2nBu, 72 (72)
i
i
8
5b: R = CO2 Bu
60 1.5 d 6b: R = CO2 Bu, 90 (77)
60 1.5 d 6c: R = CO2Cy, 87 (86)
9
5c: R = CO2Cyf
It should be noted that the bromo moieties in substrates
are tolerable under the present PdII/Pd0 catalysis.9 These
moieties can be employed in further functionalization. As
a preliminary trial, we examined the palladium-catalyzed
amination of the CÀBr bonds.3d,e Treatment of 3h, pro-
duced in the reaction of 1dwith 2a (entry 7 in Table 2), with
carbazole (1a) in the presence of Pd(OAc)2, PtBu3, and
tBuONa as catalyst, ligand, and base, respectively, gave a
double-aminated product 4 in 72% yield (Scheme 2). This
kind of carbazole trimer is known to be utilizable as host
material for phosphorescent devices.2a,c
In contrast to the reaction of styrenes, it has been known
that the aza-Wacker reactions of electron-deficient alkenes
such as acrylates with amides give anti-Markovnikov
adducts selectively.4a,c,g The same trend was also observed
in the reaction with carbazoles. Thus, treatment of n-butyl
10
11
5d: R = CONMe2
100
1 d 6d: R = CONMe2, >99 (98)
1 d 6e: R = CONHtBu, 87 (86)
5e: R = CONHtBu 100
a Reaction conditions: [1a]/[5]/[Pd(OAc)2]/[Ag2CO3] = 0.2:1:0.02:0.2
(in mmol), in MeCN (2 mL) under N2, unless otherwise noted. b GC yield
based on the amount of 1a used. Value in parentheses indicates yield after
purification. c Cu(OAc)2 H2O (0.4 mmol) was used in place of Ag2CO3.
3
d Cu(OAc)2 H2O (0.04 mmol) was used in place of Ag2CO3. e Under air.
3
f Cy = cyclohexyl.
acrylate (5a) with 1a under standard conditions using
Pd(OAc)2 (10 mol %) and Ag2CO3 (1 equiv) in MeCN
at 100 °C for 6 h exclusively gave (E)-n-butyl 3-(9H-
carbazol-9-yl)acrylate (6a) in 63% yield, no regioisomer
being detected by GC and GCÀMS (entry 1 in Table 3).
Under conditions using a stoichiometric amount of Cu-
(OAc)2 H2O (entry 2) or a catalytic amount of Cu(OAc)2
H2O under air (entry 3) as oxidant in place of Ag2CO3, the
product yield considerably decreased. Decreasing reaction
temperature was found to enhance the yield. Thus, 6a was
3
3
(9) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem.,
Int. Ed. 2009, 48, 5094.
Org. Lett., Vol. XX, No. XX, XXXX
C

also be employed for the anti-Markovnikov addition to
produce 6d and 6e efficiently (entries 10 and 11).
Scheme 3
Since carbazole is known to readily add to electron-
deficient alkenes under mild conditions even in the absence of
any catalyst,10 it is possible that 6 was produced through
the initial nucleophilic addition of 1a to 5 to form an inter-
mediate C and subsequent its dehydrogenation (Scheme 3).
However, the dehydrogenation of separately synthesized 7
did not proceed at all under standard conditions: 7 being
completely intact even after 1 d. Therefore, the stepwise route
involving the intermediary formation of 7 can be ruled out.
In summary, we have demonstrated that the palladium-
catalyzed aza-Wacker reaction of carbazoles with alkenes
proceeds efficiently to give the corresponding N-vinylated
carbazoles. Markovnikov- and anti-Markovnikov adducts
could be exclusively prepared in the reactions with styrenes
and acrylates, respectively.
obtained in 72% yield at 80 °C (entry 4). Moreover,
although the reaction was retarded at 60 °C, the yield
of 6a reached 90% after 1.5 d (entry 6). Even at room
temperature, 6a was obtained in 72% yield upon treatment
for 8 d (entry 7). At 60 °C, 1a also coupled with isobutyl
and cyclohexyl acrylates5band 5ctogive6band 6cingood
yields (entries 8 and 9). Acrylamides 5d and 5e could
Acknowledgment. This work was partly supported by
Grants-in-Aid from MEXT, JSPS, and JST, Japan.
Supporting Information Available. Standard experi-
mental procedure and characterization data of products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(10) Ferorelli, S.; Abate, C.; Colabufo, N. A.; Niso, M.; Inglese, C.;
Berardi, F.; Perrone, R. J. Med. Chem. 2007, 50, 4648.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX