Synthesis of N-substituted carbazolones from α-iodo enaminones via Pd(0)-catalyzed intramolecular coupling under microwave irradiation

Article abstract of DOI:10.1016/j.tetlet.2012.07.009

A variety of N-aryl and N-alkyl carbazolones were conveniently achieved in good to high yields via Pd₂(dba)₃-mediated intramolecular coupling of N-substituted α-iodo enaminones under microwave irradiation. The Pd(0)-catalyzed cyclization was found to proceed favorably with the more electron-deficient phenyl ring during the reactions involving unsymmetrical N,N-diaryl α-iodo enaminones. This unique property enables the construction of carbazolone skeleton containing nitro substituted benzenoid ring.

Full text of DOI:10.1016/j.tetlet.2012.07.009

Tetrahedron Letters 53 (2012) 5076–5080
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of N-substituted carbazolones from
a
-iodo enaminones via
Pd(0)-catalyzed intramolecular coupling under microwave irradiation
⇑
⇑
Xi-Liu Yun, Wen-Ying Bi, Jian-Hui Huang, Yu Liu, Daisy Zhang-Negrerie, Yun-Fei Du , Kang Zhao
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of N-aryl and N-alkyl carbazolones were conveniently achieved in good to high yields via
Pd2(dba)3-mediated intramolecular coupling of N-substituted -iodo enaminones under microwave irra-
diation. The Pd(0)-catalyzed cyclization was found to proceed favorably with the more electron-deficient
phenyl ring during the reactions involving unsymmetrical N,N-diaryl -iodo enaminones. This unique
Received 7 May 2012
Revised 22 June 2012
Accepted 3 July 2012
Available online 15 July 2012
a
a
property enables the construction of carbazolone skeleton containing nitro substituted benzenoid ring.
Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
Keywords:
N-Substituted a-iodo enaminones
N-Substituted carbazolones
Pd2(dba)3
Microwave irradiation
C–C bond formation
N-Substituted carbazolone moieties, including both N-alkylated
and N-arylated ones, have been found as important basic building
blocks in many synthetic drugs,1 natural products,2 and biologi-
cally active compounds.3
O
O
c
: oxidative
N
R
NH
a
: Fischer
N
R
O coupling
Indole
Generally, the N-substituted carbazolones can be synthesized
from N-unsubstituted carbazolones via base-mediated alkylation4
or SNAr arylation.5 Alternatively, N-substituted enaminones pro-
vide an expedient access to N-substituted carbazolones via C–C
bond formation.6,7 For example, Fisher indole synthesis was appli-
cable to the synthesis of N-phenyl and N-aroyl carbazolones (Fig. 1,
path a).8 Surprisingly, literature survey indicates that this approach
has never been applied to the synthesis of N-alkyl carbazolones.
Another method that can also lead to the formation of carbazolone
ring, is the Heck reaction, via Pd(0)-mediated C–C bond formation
(Fig. 1, path b).9 However, this approach is seldom applied to the
synthesis of N-aryl carbazolones, possibly because the N-arylation
of the enaminone substrates at an early stage is not a desirable pro-
cess. The third commonly applied method is by the direct oxidative
C–C coupling through palladium-catalyzed6 or photochemical
reaction,7 which is considered as a powerful tool for the carbazo-
lone formation since no halogen atom is needed for the cyclization
to occur (Fig. 1, path c). However, this method also suffers its lim-
itation in synthesis of N-aryl carbazolones.
R = H or alkyl
R = H, phenyl,
or aroyl
N
R
b
: Heck
Pd (0)
O
O
I
Pd (0)
X
N
R
N
R
R = Aryl or alkyl
R = H or alkyl
X = I, Br, Cl
d This paper
:
Figure 1. Methods for the formation of carbazolone skeletons via the strategy of C–
C bond formation.
Herein, we report an alternative synthesis of N-substituted car-
bazolones, including both N-aryl and N-alkyl carbazolones, from N-
substituted
molecular coupling. Differing from the classical Heck substrates,9
the iodo substituent in the reactants is substituted on the -posi-
a
-iodo N-aryl enaminones10 via Pd(0)-catalyzed intra-
a
tion of the cyclohexenone ring, rather than the phenyl ring, in
our reaction (Fig. 1, path d).
In our previous work, we described the formation of a variety of
N-aryl
ily available 3-aminocyclohex-2-enones via concurrent
ation and N-arylation mediated by ArI(OAc)2 (2) (see Scheme 1).10
a
-iodo enaminones 3, obtained in high yields from the read-
⇑
Corresponding authors. Tel./fax: +86 022 27404031.
E-mail addresses: duyunfeier@tju.edu.cn (Y.-F. Du),
a-iodin-
kangzhao@tju.edu.cn
(K. Zhao).
0040-4039/$ - see front matter Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.009

X.-L. Yun et al. / Tetrahedron Letters 53 (2012) 5076–5080
5077
O
time and therefore improve the yield by minimizing the formation
of byproducts. A gratifying 91% yield was successfully achieved by
carrying out the reaction under microwave irradiation (400 W,
80 °C) for 30 min (Table 1, entry 11). Further attempts to improve
either the catalytic activity or the yield with other palladium re-
agents were unsuccessful (Table 1, entries 11–15).
O
AcO
R2
I OAc
I
R2
DCE
R1
+
60 °C
N
N
H
R1
1
2
3
R1 = aryl, alkyl; R2 = H, Cl, Br, NO2, CO2Me
Under the optimized reaction conditions (Table 1, entry 10),
the scope of this transformation was investigated. Results in Table
2 show that this catalytic system displays great tolerance to a
variety of functional groups such as chloro, bromo, nitro, methyl,
methoxy, and ester substituents on the phenyl ring in the sub-
strates. Enaminones without any substituent on the phenyl rings
can undergo cyclization smoothly to furnish N-phenyl carbazol-
ones 4a and 4b in high yields (Table 2, entries 1–2). The enami-
none substrates bearing weak electron-withdrawing substituents
such as chloro and bromo groups at the phenyl ring also afforded
the corresponding carbazolone products in good yields (entries 3–
Scheme 1. Formation of N-substituted
and ArI(OAc)2 2.
a-iodo enaminones 3 from enaminone 1
Building on this work, we launch the research of finding new meth-
ods to convert these N-aryl and N-alkyl -iodo enaminones 3 to the
a
more useful carbazolone derivatives through ring closure via palla-
dium(0)-mediated intramolecular C–C bond formation.11
We began our investigation by carrying out an extensive
screening of the variables to identify the optimal conditions for this
conversion. Considering that the N-substituted a-iodo enaminones
4, Table 2). When the unsymmetric N,N-diaryl
a-iodo enaminone
3 in our study are similar to the substrate in Heck reactions, we se-
lected Pd2(dba)3 as the initial catalyst in anticipation of a similar
oxidative insertion of the generated Pd(0) species into the C–I bond
in the first step. Our experiments revealed that substrate 3a in-
deed, underwent cyclization in the presence of Pd2(dba)3 and
KOH in dry DMF,12 albeit the desired product 4a was obtained in
only 12% yield (entry 1, Table 1). Encouraged by this initial result,
we continue our research by investigating a variety of other bases
(Table 1, entries 2–4). To our pleasant surprise, a good isolated
yield of 70% of the desired product was achieved when Et3N was
used as base and the reaction heated at 80 °C for 12 h (Table 1, en-
try 4). Further solvent screening study showed that none of the
other solvents, including DMA, CH3CN, Et3N, dioxane, or toluene
provide any better result (Table 1, entries 5–9). Considering that
the reaction was heated at 80 °C for 12 h, we thought that the
application of microwave irradiation13 might shorten the reaction
3e was applied, it was found that the cyclization occurred exclu-
sively with the unsubstituted phenyl ring to give product 4e in
good yield (Table 2, entry 5), which implies that this Pd(0)-med-
iated cyclization process does not favor the electron-rich phenyl
ring. Similarly, for the unsymmetric methoxy-substituted
substrate 3f, the electron-rich phenyl ring was inert and the cycli-
zation afforded carbazolones 4f as the sole product (entry 6,
Table 2).
In the previous synthesis of carbazolones, the enaminone sub-
strates bearing the nitro group on the phenyl ring seldom under-
went the Pd-mediated annulation.14 Remarkably, our reaction is
applicable to the
a-iodo enaminones that bear strong electron-
withdrawing groups such as nitro group. For example, the desired
cyclized product 4g can be obtained from nitro-substituted sub-
strate 3g in 30% yield (Table 2, entry 7), along with the formation
of the 3-(bis(4-nitrophenyl)amino)phenol as the major byprod-
uct.15 In addition to the similar byproduct resulted from the deha-
logenative aromatization of iodo cyclohexenone,15 the para-nitro
substituted enaminone 3h was found to selectively give N-phenyl
carbazolone 4h as the sole cyclized product, which further indi-
cates that this cyclization process favors the more electron-defi-
cient phenyl ring (entry 8, Table 2). Moreover, enaminone 3i
bearing the meta-nitro substituent afforded 4i as the only regio-
isomer and in a relatively better yield (Table 2, entry 9). Consider-
ing that the unexpected aromatization was always the
concomitant side reaction for these nitro-substituted enaminones,
we came to use the nitro-substituted enaminone 3j, with two
methyl groups substituted on the same carbon of the cyclohexe-
none ring, in the hope of preventing the side reaction of aromatiza-
tion. As expected, the desired cyclized 4j was formed in a
satisfactory 70% yield (Table 2, entry 10).
Table 1
Reaction condition optimization for the intramolecular cyclization of 3-(diphenyl-
amino)-2-iodo-cyclohex-2-enone 3aa
O
O
I
catalyst, base
solvent, 80 °C
N
N
3a
4a
Entry
Pd catalyst
Base
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd(OAc)2/PPh3
PdCl2/PPh3
PdCl2/dppf
PdCl2/dppe
PdCl2/BINAP
KOH
K2CO3
KOAc
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
DMF
DMF
DMF
DMF
DMA
CH3CN
Et3N
Dioxane
Toluene
DMF
1
1
12
10
25
70c
65
30
<5d
20
<5
91
43
85
34
<5
10
1.5
12
12
12
12
12
12
0.5
0.5
0.5
1.0
0.5
0.5
This method can also be used in synthesizing N-heteroaryl car-
bazolone compounds. a-Iodo enaminone 3k, in which one phenyl
ring is replaced by a substituted thienyl ring, was also converted
to the carbazolone product 4k in moderate yield under the condi-
tions (entry 11, Table 2). Notably, the reaction was also applicable
to the preparation of N-alkyl carbazolones. Subjecting N-alkyl
a-
10e
11e,f
12e,f
13e,f
14e,f
15e,f
iodo enaminone 3l and 3m to the identical conditions was found
to give the corresponding N-alkyl carbazolones 4l and 4m, respec-
tively, in good yields (Table 2, entries 12–13).
The scope of the substrates can be further broadened by chang-
ing the cyclohexenone ring to a five-membered cyclopentenone
ring or seven-membered cycloheptenone ring. Homologues 6a
DMF
DMF
DMF
DMF
DMF
a
Reaction conditions: 3a (0.26 mmol), Pd catalyst (5 mol%) and base (0.65 mmol)
in 300 L of solvent at 80 °C.
l
and 6b could be accessed from the corresponding
a-iodo enami-
b
Isolated yields.
82% conversion.
18% conversion.
Under microwave irradiation (400 W, 80 °C).
15 mol% of ligand was used.
c
d
e
f
nones 5a and 5b, respectively. However, the yields were inferior
to that of 4a, which possibly resulted from the higher ring strain
existing in substrates 5a and 5b, and even more so in products
6a and 6b (Scheme 2).

5078
X.-L. Yun et al. / Tetrahedron Letters 53 (2012) 5076–5080
Table 2
Synthesis of N-substituted carbazolones 4a
O
O
I
Pd2(dba)3, Et3N
R2
R2
DMF, 80 °C
mw (400 W)
N
N
R1
R1
4
3
Entry
1
Enaminones 3
Carbazolones 4
Yieldb (%)
O
O
I
91
N
N
3a
4a
O
O
I
2
3
88
87
N
N
4b
O
3b
O
O
O
Cl
I
Cl
N
N
4c
3c
Cl
I
Cl
O
Br
Br
N
N
4
5
6
77
80
75
4d
3d
Br
I
Br
O
Me
N
N
3e
4e
Me
N
O
O
I
MeO
O2N
O2N
N
3f
4f
OMe
O
O
I
O2N
N
N
7
8
30
45
3g
4g
4h
NO2
NO2
N
O
O
I
O2N
N
3h

X.-L. Yun et al. / Tetrahedron Letters 53 (2012) 5076–5080
5079
Table 2 (continued)
Entry
Enaminones 3
Carbazolones 4
Yieldb (%)
O
O
O
O
I
9
60
N
N
N
O2N
O2N
O2N
O2N
3i
4i
I
N
10
70
3j
4j
O
O
I
11
12
65
80
N
N
CO2Me
CO2Me
3k
O
4k
S
S
O
MeO2C
MeO2C
I
MeO2C
MeO2C
N
N
N
4l
3l
O
O
I
N
13
84
3m
4m
lL of dry DMF at 80 °C under microwave
a
Reaction conditions: 3 (0.26 mmol), Pd2(dba)3 (5 mol %), and Et3N (0.65 mmol) in 300
irradiation (400 W) for 30 min.
b
Isolated yields.
O
O
O
O
I
I
R2
R2
n
Pd2dba3, Et3N
n
N
N
N
R1
DMF, 80 °C
mw (400), 0.5 h
R1
N
LnPd(0)
O
3
4
oxidative
LnPd(0)
reductive
addition
elimination
5a (n = 0)
5b (n = 2)
53%
65%
6a (n = 0)
Ln
Pd
I
O
6b
(n = 2)
Ln
Pd
R2
R2
Scheme 2. Further application of the method for the synthesis of carbazolone
N
N
homologues.
R1
III
R1
I
σ - bond
I
O
Ln
metathesis
H
HI
We propose that this Pd(0)-mediated cyclization process adopts
the mechanistic sequence shown in Scheme 3.16 Initially, the oxi-
dative insertion of Pd(0) into the C(sp2)–I bond leads to intermedi-
ate I. Then, the activation of the aromatic C–H bond takes place via
Pd
Et3N
R2
N
Et3NHI
R1
II
r
-bond metathesis (through the transition state of II) to generate
Scheme 3. Plausible reaction mechanism.
the six-membered palladium complex III, with the released HI
being neutralized by Et3N.6c Finally, reductive elimination occurs
to afford the carbazolone products and regenerate the reactive
Pd(0) species. An alternative mechanistic pathway involving elec-
trophilic aromatic palladation17 was not proposed since the corre-
sponding carbocation intermediates generated are unstable for
these nitro-substituted substrates.14b
Our experimental results clearly demonstrate that the Pd(0)-
mediated cyclization is preferential to the more electron-deficient
aryl rings. We tentatively propose that the acidity of the aromatic
C(sp2)-H in intermediate II is the key factor that determines this
regioselectivity: the more acidic aromatic C(sp2)-H enables a fast
r
-bond metathesis in intermediate II. The reason for the inferior
yield of 4h, compared with 4i, is likely due to the fact that the aro-
matic C(sp2)-H substituted at the meta position is less acidic than
that at the para position.
In summary, we have developed an alternative and comple-
mentary approach to the synthesis of N-substituted carbazolones
via Pd(0)-catalyzed intramolecular coupling of
a-iodo enaminon-
es.18 The protocol can provide both N-aryl and N-alkyl carbazol-
ones with various substitution patterns in good to excellent
yields. Notably, the unique regioselectivity displayed in this

5080
X.-L. Yun et al. / Tetrahedron Letters 53 (2012) 5076–5080
6835–6837; (c) Pan, D.; Chen, A.; Su, Y.; Zhou, W.; Li, S.; Jia, W.; Xiao, J.; Liu, Q.;
Zhang, L.; Jiao, N. Angew. Chem., Int. Ed. 2008, 47, 4729–4732; (d) Wan, X.; Ma,
Z.; Li, B.; Zhang, K.; Cao, S.; Zhang, S.; Shi, Z. J. Am. Chem. Soc. 2006, 128, 7416–
7417; (e) Aragon, P.-J.; Chezal, J.-M.; Chavignon, O.; Teulade, J.-C.; Blache, Y.
Heterocycles 2003, 60, 551–561; (f) Laschober, R.; Kappe, T. Synthesis 1990,
387–388; (g) Mckillop, A.; Kemp, D. Tetrahedron 1989, 45, 3299–3306.
12. For selected reviews on screening the optimal conditions for palladium-
catalyzed synthesis of carbazolones, see: (a) Koutentis, P. A.; Loizou, G.; Lo Re,
D. J. Org. Chem. 2011, 76, 5793–5802; (b) Shi, Z.; Ding, S.; Cui, Y.; Jiao, N. Angew.
Chem., Int. Ed. 2009, 48, 7895–7898; (c) Beccalli, E. M.; Broggini, G.; Martinelli,
M.; Sottocornola, S. Chem. Rev. 2007, 107, 5318–5365; (d) Zeni, G.; Larock, R. C.
Chem. Rev. 2006, 106, 4644–4680; (e) Wan, X.; Xing, D.; Fang, Z.; Li, B.; Zhao, F.;
Zhang, K.; Yang, L.; Shi, Z. J. Am. Chem., Soc. 2006, 128, 12046–12047; (f) Lane, B.
S.; Brown, M. A.; Sames, D. J. Am. Chem. Soc. 2005, 127, 8050–8057; (g)
Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem. Int. Ed. 2005, 44, 4490–
4527; (h) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079–3159;
(i) Ma, S.; Jiao, N.; Zhao, S.; Hou, H. J. Org. Chem. 2002, 67, 2837–2847; (j)
Edmondson, S. D.; Mastracchio, A.; Parmee, E. R. Org. Lett. 2000, 2, 1109–1112;
(k) Lorsbach, B. A.; Kurth, M. J. Chem. Rev. 1999, 99, 1549–1581.
method enables the synthesis of carbazolone skeleton containing a
nitro-group substituted benzenoid ring.
Acknowledgments
Y. Du acknowledges the National Natural Science Foundation of
China (#21072148) and Cultivation Foundation (B) for Young Fac-
ulty of Tianjin University (TJU-YFF-08B68) for financial support.
Supplementary data
Supplementary data (list of new compounds along with their
yield and copies of 1H NMR and 13C NMR spectra) associated with
this article can be found, in the online version, at http://dx.doi.org/
10.1016/j.tetlet.2012.07.009. These data include MOL files and
InChiKeys of the most important compounds described in this
article.
13. Siamaki, A. R.; Khder, A. E. R. S.; Abdelsayed, V.; El-Shall, M. S.; Gupton, B. F. J.
Catal. 2011, 279, 1–11.
14. (a) Neumann, J. J.; Rakshit, S.; Droege, T.; Glorius, F.; Wuertz, S. Chem. Eur. J.
2011, 17, 7298–7303; (b) Weng, B.; Liu, R.; Li, J.-H. Synthesis 2010, 2926–2930.
15. The dehalogenative aromatization of the nitro-substituted cyclohexenone is
proposed to undergo the following pathway: In the presence of base, substrate
3g or 3h is isomerized into intermediate A, which is further tautomerized into
enol B. Finally, dehalogenation occurs to give the phenol compound 4g0 or 4h0.
For an example describing the similar formation of intermediate A, see:
Hayashi, Y.; Shoji, M.; Kishida, S. Tetrahedron Lett. 2005, 46, 681–685.
References and notes
1. (a) Prakash, S. R.; Cable, K. M.; Correa, I. D.; Fellows, I.; Montgomery, S.;
Newman, J. J.; Waterhouse, I.; Wells, G. N.; Sutherland, D. R. J. Labelled Compd.
Radiopharm. 1995, 36, 993–1007; (b) Yan, S.; Wu, H.; Wu, N.; Jiang, Y. Synlett
2007, 2699–2702.
2. (a) Sissouma, D.; Maingot, L.; Collet, S.; Guingant, A. J. Org. Chem. 2006, 71,
8384–8389; (b) Knölker, H.-J. Top. Curr. Chem. 2005, 244, 115; (c) Sissouma, D.;
Collet, S. C.; Guingant, A. Y. Synlett 2004, 2612–2614; (d) Knölker, H.-J.; Reddy,
K. R. Heterocycles 2003, 60, 1049–1052; (e) Bouaziz, Z.; Nebois, P.; Poumaroux,
A.; Fillion, H. Heterocycles 2000, 52, 977–999; (f) Chakraborty, D. P.;
Chowdhury, B. K. J. Org. Chem. 1968, 33, 1265–1268.
3. (a) Barta, T. E.; Veal, J. M.; Rice, J. W.; Partridge, J. M.; Fadden, R. P.; Ma, W.;
Jenks, M.; Geng, L.; Hanson, G. J.; Huang, K. H.; Barabasz, A. F.; Foley, B. E.; Otto,
J.; Hall, S. E. Bioorg. Med. Chem. Lett. 2008, 18, 3517–3521; (b) Masaguer, C. F.;
Formoso, E.; Ravin´ a, E.; Tristán, H.; Loza, M. I.; Rivas, E.; Fontenla, J. A. Bioorg.
Med. Chem. Lett. 1998, 8, 3571–3576.
O
O
OH
I
I
I
Et3N
O2N
O2N
O2N
N
R
N
R
N
R
B
A
3g or 3h
OH
Et3N
- HI
4g'
(4-NO2, R = 4-NO2Ph) 52%
4h' (4-NO2, R = Ph) 47%
O2N
N
R
4. (a) Sato, M.; Suzuki, Y.; Yamada, F.; Somei, M. Heterocycles 2010, 80, 1027–
1045; (b) McErlean, C. S. P.; Sperry, J.; Blake, A. J.; Moody, C. J. Tetrahedron 2007,
63, 10963–10970; (c) Li, X.; Vince, R. Bioorg. Med. Chem. Lett. 2006, 14, 2942–
2955; (d) Romeo, G.; Materia, L.; Pittalà, V.; Modica, M.; Salerno, L.; Siracusa,
M.; Russo, F.; Minneman, K. P. Bioorg. Med. Chem. Lett. 2006, 14, 5211–5219; (e)
16. One reviewer has proposed the following alternative mechanism, which
involves carbopallation of the aromatic ring followed by anti-elimination of
HPdI. For a representative example, see: Toyota, M.; Ilangovan, A.; Okamoto, R.;
Masaki, T.; Arakawa, M.; Ihara. M. Org. Lett. 2002, 4, 4293–4296.
ˇ
Desmaele, D.; DAngelo, J. J. Org. Chem. 1994, 59, 2292–2303.
5. Barta, T. E.; Barabasz, A. F.; Foley, B. E.; Geng, L.; Hall, S. E.; Hanson, G. J.; Jenks,
M.; Ma, W.; Rice, J. W.; Veal, J. Bioorg. Med. Chem. Lett. 2009, 19, 3078–3780.
6. (a) Bi, W.; Yun, X.; Fan, Y.; Qi, X.; Du, Y.; Huang, J. Synlett 2010, 2899–2904; (b)
Knölker, H.-J. Chem. Lett. 2009, 8–13; (c) Würtz, S.; Rakshit, S.; Neumann, J. J.;
Dröge, T.; Glorius, F. Angew. Chem. Int. Ed. 2008, 47, 7230–7233; (d) Knölker, H.-
J.; Reddy, K. R. Chem. Rev. 2002, 102, 4303–4427; (e) Mithani, S.; Weeratunga,
G.; Taylor, N. J.; Dmitrienko, G. I. J. Am. Chem. Soc. 1994, 116, 2209–2210.
7. (a) Aragon, P.-J.; Yapi, A.-D.; Pinguet, F.; Chezal, J.-M.; Teulade, J.-C.; Blache, Y.
Chem. Pharm. Bull. 2007, 55, 1349–1355; (b) Tietcheu, C.; Garcia, C.; Gardette,
D.; Dugat, D.; Gramain, J. J. Heterocycl. Chem. 2002, 39, 965–973.
I
I
O
O
Pd
O
Pd
H
carbopalladation
- HPdI
R2
N
N
R2
R2
N
R1
R1
R1
8. For selected examples of synthesis of carbazolones via Fischer synthesis, see (a)
Xu, D.-Q.; Wu, J.; Luo, S.-P.; Zhang, J.-X.; Wu, J.-Y.; Du, X.-H.; Xu, Z.-Y. Green
Chem. 2009, 11, 1239–1246; (b) Kudzma, L. V. Synthesis 2003, 1661–1666; (c)
Rodriguez, J.-G.; Temprano, F.; Esteban-Calderon, C.; Martinez-Ripoll, M. J.
Chem. Soc. Perkin Trans. 1 1989, 2117–2122; (d) Baldwin, J. E.; Tzodikov, N. R. J.
Org. Chem. 1977, 42, 1878–1883; (e) Sucrow, W.; Slopianka, M.; Mentzel, C.
Chem. Ber. 1973, 106, 745–750.
9. For selected examples of synthesis of carbazolones via Heck reaction, see: (a)
Janreddy, D.; Kavala, V.; Bosco, J. W. J.; Kuo, C.-W.; Yao, C.-F. Eur. J. Org. Chem.
2011, 12, 2360–2365; (b) Sorensen, U. S.; Pombo-Villar, E. Helv. Chim. Acta
2004, 87, 82–89; (c) Masaguer, C. F.; Ravina, E.; Fontenla, J. A.; Brea, J.; Tristan,
H.; Loza, M. I. Eur. J. Med. Chem. 2000, 35, 83–95; (d) Wang, H.-M.; Chou, H.-L.;
Chen, L.-C. J. Chin. Chem. Soc. Taip. 1995, 42, 593–595; (e) Sakamoto, T.; Nagano,
T.; Kondo, Y.; Yamanaka, H. Synthesis 1990, 215–218; (f) Iida, H.; Yuasa, Y.;
Kibayashi, C. J. Org. Chem. 1980, 45, 2938–2942.
17. For selected examples of electrophilic aromatic palladation, see: (a) Campeau,
L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006, 128, 581–590; (b)
Tunge. J. A.; Foresee, L. N. Organometallics 2005, 24, 6440–6444.; (c) Park, C.-H.;
Ryabova, V.; Seregin, I. V.; Sromek, A. W.; Gevorgyan, V. Org. Lett. 2004, 6,
1159–1162; (d) Glover, B.; Harvey, K. A.; Liu, B.; Sharp, M. J.; Tymoschenko, M.
F. Org. Lett. 2003, 5, 301–304; (e) González, J. J.; García, N.; Gómez-Lor, B.;
Echavarren, A. M. J. Org. Chem. 1997, 62, 1286–1291; (f) Li, C.-S.; Jou, D.-C.;
Cheng, C.-H. Organometallics 1993, 12, 3945–3954.
18. General procedure for the Synthesis of N-substituted carbazolones 4a–m and 6a–
b: A mixture of
a-iodo enaminones 3a–m, 5a–b (0.26 mmol), Pd2(dba)3 (5 mol
%), Et3N (0.65 mmol), and anhydrous DMF (300
lL) was stirred at 80 °C under
microwave (400 W) for 30 min. After the consumption of the starting material,
the mixture was cooled to room temperature, filtered to remove the solid
materials. The filtrate was extracted with EtOAc (20 mL ꢀ 3). The organic phase
was combined, dried with anhydrous Na2SO4, and evaporated to remove the
solvent. The residue was purified by flash column chromatography (EtOAc/PE)
on silica gel to give the desired products 4a–m, 6a–b.
10. Chen, Y.; Ju, T.; Wang, J.; Yu, W.; Du, Y.; Zhao, K. Synlett 2010, 231–
234.
11. (a) Shi, Z.; Zhang, B.; Cui, Y.; Jiao, N. Angew. Chem., Int. Ed. 2010, 49, 4036–4041;
(b) Jin, Y. L.; Kim, S.; Kim, Y. S.; Kim, S.-A.; Kim, H. S. Tetrahedron Lett. 2008, 49,