Rh(iii)-Catalyzed dual C-H functionalization of 3-(1: H -indol-3-yl)-3-oxopropanenitriles with sulfoxonium ylides or diazo compounds toward polysubstituted carbazoles

Article abstract of DOI:10.1039/c8ob02145g

A rhodium-catalyzed annulation of 3-(1H-indol-3-yl)-3-oxopropanenitriles with sulfoxonium ylides or diazo compounds has been developed, leading to a series of polysubstituted carbazoles in moderate to good yields. This procedure proceeded with formal Rh(iii)-catalyzed (4 + 2) cycloaddition, with the functionalization of 2-C-H bonds of indole in a step-economical procedure. Additionally, this reaction could also be conducted under acidic conditions when diazo compounds were employed as the reaction partners, which was a complement to the annulation of sulfoxonium ylides under weak basic conditions.

Full text of DOI:10.1039/c8ob02145g

Organic &
Biomolecular Chemistry
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COMMUNICATION
Rh(III)-Catalyzed dual C–H functionalization of
3-(1H-indol-3-yl)-3-oxopropanenitriles with
sulfoxonium ylides or diazo compounds toward
polysubstituted carbazoles†
Cite this: Org. Biomol. Chem., 2018,
16, 8715
Received 31st August 2018,
Accepted 1st November 2018
DOI: 10.1039/c8ob02145g
Yan Xiao, Hao Xiong, Song Sun,
Jintao Yu
and Jiang Cheng
*
rsc.li/obc
A rhodium-catalyzed annulation of 3-(1H-indol-3-yl)-3-oxopropa- ylides12 as a C4 synthon leading to naphthalene frameworks
nenitriles with sulfoxonium ylides or diazo compounds has been (Scheme 1, eqn (1)).13,14 In 2017, Wang and co-workers
developed, leading to a series of polysubstituted carbazoles in reported a pioneering work for the synthesis of carbazoles
moderate to good yields. This procedure proceeded with formal from
Rh(III)-catalyzed (4 + 2) cycloaddition, with the functionalization of oxopropanenitriles with alkynes catalyzed by rhodium
2-C–H bonds of indole in
step-economical procedure. (Scheme 1, eqn (2)).15 We herein report an efficient strategy to
the
cascade
reaction
of
3-(1H-indol-3-yl)-3-
a
Additionally, this reaction could also be conducted under acidic access polysubstituted carbazoles via Rh(III)-catalyzed C–H acti-
conditions when diazo compounds were employed as the reaction vation with sulfoxonium ylides or diazo compounds
partners, which was a complement to the annulation of sulfoxo- (Scheme 1, eqn (3)).
nium ylides under weak basic conditions.
We initiated our work via exploring the reaction of 3-(1H-
indol-3-yl)-3-oxopropanenitriles 1a (0.1 mmol) and sulfoxo-
nium ylide 2a (0.12 mmol) in the presence of [Cp*Rh(MeCN)3]
(SbF6)2 (5 mol%), and NaOAc (0.2 mmol) as the additive in
DCE at 100 °C for 12 h (Table 1). To our delight, the annula-
tion product 3 was isolated in 31% yield (entry 1). [Cp*Co(CO)
I2] and Pd(OAc)2 resulted in no reaction (entries 2 and 3). In
contrast, [Cp*IrCl2]2, [Cp*Rh(OAc)2]2 and [Cp*RhCl2]2
Carbazoles are important structural scaffolds of many bio-
active natural products,1 light-emitting materials2 and organic
dyes.3 Moreover, they show antimalarial4 and antitumor activi-
ties.5 For example, rebeccamycin and its analogues such as
NSC655649 have been permitted into clinical trials for treat-
ment of cancer.6 Carbazoles also serve as building blocks of
functional materials, such as conjugated polymers, which
possess light-emitting properties that allow for the detection
of diverse chemicals.7
As such, great attention has been paid to the synthesis of
such frameworks. There are two general pathways based on
the construction of a ring in carbazoles. One is the construc-
tion of a middle pyrrole ring via the intramolecular C–N bond
formation in the ortho-substituted biphenyl starting material.8
Alternatively, the other involves the construction of a new aro-
matic ring toward benzo-indole, namely carbazole via benzan-
nulation.9 From the diversity and complexity of the product
point of view, this version attracted increasing interest of
organic chemists.
Recently, phenyl 3-oxopropanenitriles were well developed
in the annulation with diazo compounds10,11 and sulfoxonium
School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic
Materials & Technology, Changzhou University, Changzhou 213164, P. R. China.
E-mail: jiangcheng@cczu.edu.cn
†Electronic supplementary information (ESI) available. CCDC 1848812. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c8ob02145g
Scheme 1 The annulation of aryl 3-oxopropanenitriles toward fused
aromatics.
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Table 1 Screening the optimal conditionsa
Entry
Catalyst
Additive
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
[Cp*Rh(MeCN)3](SbF6)2
[Cp*Co(CO)I2]
Pd(OAc)2
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
LiOAc
DCE
DCE
DCE
DCE
DCE
DCE
MeCN
DMF
EtOH
THF
THF
THF
THF
THF
THF
31
n.r.
n.r.
46
49
55
[Cp*IrCl2]2
[Cp*Rh(OAc)2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
69
73
41
9
10
11
12
13
14
15
70c, 83, 77d
72
CsOAc
HOAc
Cu(OAc)2
AgOAc
78
n.r.
<10
n.r.
a Reaction conditions: 3-(1H-Indol-3-yl)-3-oxopropanenitriles 1a
(0.1 mmol), sulfoxonium ylide 2a (0.12 mmol), [Cp*RhCl2]2 (5 mol%),
additive (0.2 mmol), solvent (2.0 mL), N2 (1.0 atm), at 100 °C for 12 h,
c
in
a
sealed Schlenk tube. b Isolated yield. 1a (0.1 mmol), 2a
(0.1 mmol). d 1a (0.1 mmol), 2a (0.15 mmol).
Scheme 2 Scope of substituted 3-(1H-indol-3-yl)-3-oxopropaneni-
triles. Reaction conditions: 3-(1H-Indol-3-yl)-3-oxopropanenitriles
1
(0.1 mmol), sulfoxonium ylide 2a (0.12 mmol), [Cp*RhCl2]2 (5 mol%),
additive (0.2 mmol), solvent (2.0 mL), N2 (1.0 atm), at 100 °C for 12 h, in
a sealed Schlenk tube.
increased the yields to 46%, 49% and 55%, respectively
(entries 4–6). During solvent screening, THF (83%) was
superior to DCE (55%), MeCN (69%), DMF (73%) and EtOH
(41%, entries 7–10). Changing the ratio of 1a and 2a to 1 : 1 or 3ag in 76%, 78% and 75% yields, respectively. Moreover, sul-
1 : 5 decreased the reaction efficiency (entry 10). NaOAc was foxonium ylides possessing a cyclohexyl group or fused hetero-
the best additive in the transformation (entries 11 and 12) cyclic ring were also investigated, which provided the corres-
while HOAc, Cu(OAc)2, and AgOAc inhibited the reaction ponding carbazoles in acceptable yields (3ah–ak, 58–69%).
(entries 13–15). Finally, the optimized reaction conditions Notably, some reactive groups, such as fluoro (3al) and chloro
were selected as follows: 1 (0.1 mmol), 2 (0.12 mmol), (3am) groups, which are suitable for further potential
[Cp*RhCl2]2 (5 mol%), and NaOAc (0.2 mmol) in THF (2.0 mL) functionalization, survived well in these reactions.
at 100 °C for 12 h under an inert atmosphere (N2).
This procedure was also applicable to diazo compounds by
With the optimized reaction conditions identified, the slightly changing the reaction parameters as follows:
scope and limitation of 3-(1H-indol-3-yl)-3-oxopropanenitriles [RhCp*Cl2]2 (5 mol%) and HOAc (2.0 equiv.) at 100 °C in THF
were studied, as shown in Scheme 2. Generally, this procedure under the atmosphere of N2 (Scheme 4). Generally, it was
was compatible with 3-(1H-indol-3-yl)-3-oxopropanenitriles found that diazo compounds bearing different substituents
bearing both electron-donating and withdrawing groups in the could afford their corresponding products in good yields
phenyl ring in moderate to good yields (62–83%, 3aa–ja). (5aa–ae, 72–85%). The structure of 5ae was further confirmed
Notably, the analogues bearing functional groups such as by X-ray crystallography (Scheme 4).16 In this case, the reaction
fluoro, chloro, bromo, methyl, and methoxy worked well with was performed under acidic conditions, which was a comp-
sulfoxonium ylides for the regioselective construction of carba- lement to the aforementioned Rh-catalyzed annulation of sul-
zoles. Typically, 3-(1-methyl-1H-indol-3-yl)-3-oxopropanenitrile foxonium ylides under weak basic conditions.
1j could also react with 2a smoothly to generate the corres-
ponding product 3ja in 81% yield.
In conclusion, we have developed a novel and step-economi-
cal method to access substituted carbazoles from readily acces-
Next, various substituted sulfoxonium ylides were examined sible indoles and sulfoxonium ylides or diazo compounds
(Scheme 3). Once again, the reaction efficiency was not sensi- through a formal Rh(III)-catalyzed (4 + 2) cycloaddition. The
tive to the electronic properties of the groups on the sulfoxo- scope of 3-(1H-indol-3-yl)-3-oxopropanenitriles and sulfoxo-
nium ylides (3ab–am, 56–78%). Notably, sulfoxonium ylides nium ylides was found to be broad. Further applications of
with the phenyl ring substituted with methyl at the ortho, this method will be investigated in the synthesis of related
meta, and para positions worked well to afford 3ae, 3af and fused structures.
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Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We thank the National Natural Science Foundation of China
(no. 21572025), the “Innovation & Entrepreneurship Talents”
Introduction Plan of Jiangsu Province, the Key University
Science Research Project of Jiangsu Province (15KJA150001),
the Jiangsu Key Laboratory of Advanced Catalytic Materials &
Technology (BM2012110) and the Advanced Catalysis and
Green Manufacturing Collaborative Innovation Center for
financial support. Sun thanks the National Natural Science
Foundation of China (no. 21602019) and the Young Natural
Science Foundation of Jiangsu Province (BK20150263) for
financial support.
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