Catalytic Oxidative Coupling Cyclization for Construction of Benzofuroindolenines under Mild Reaction Conditions

Article abstract of DOI:10.1002/adsc.201801184

We describe iron-catalyzed oxidative coupling cyclization of tetrahydrocarbazoles or THβCs or THγCs to form benzofuroindolenines as fused polycyclic indoles. This mild, efficient and simple approach afforded a library of more than 52 complex compounds across a range of substrate classes with good to excellent yields. (Figure presented.).

Full text of DOI:10.1002/adsc.201801184

Title: Catalytic Oxidative Coupling Cyclization for Construction of
Benzofuroindolenines under Mild Reaction Conditions
Authors: Yuqi Lin, Jinxiang Ye, Wenting Zhang, Yu Gao, and Haijun
Chen
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801184
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Advanced Synthesis & Catalysis
10.1002/adsc.201801184
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Catalytic Oxidative Coupling Cyclization for Construction of
Benzofuroindolenines under Mild Reaction Conditions
a,†
a,†
a
a
a,
Yuqi Lin, Jinxiang Ye, Wenting Zhang, Yu Gao, and Haijun Chen *
a
College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China Email: chenhaij@gmail.com
These authors contributed equally to this work.
†
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. We describe iron-catalyzed oxidative coupling
cyclization of tetrahydrocarbazoles or THβCs or THγCs to (THβCs) and tetrahydro-γ-carbolines (THγCs) with
form benzofuroindolenines as fused polycyclic indoles. This
mild, efficient and simple approach afforded a library of
more than 52 complex compounds across a range of substrate
classes with good to excellent yields.
Tetrahydrocarbazoles,
tetrahydro-β-carbolines
[16]
attractive pharmacological potentials, are common
core natural products and
motifs [17]in
pharmaceuticals. These scaffolds have become an
interesting starting point for direct functionalization
[18]
in organic and medicinal chemistry. Recently, we
reported a biomimetic oxidative coupling cyclization
for rapid construction of isochromanoindolenines via
efficient functionalization of THβCs or THγCs with
Keywords: catalytic oxidative coupling cyclization;
benzofuroindolenines; fused polycyclic indoles; open flask
[
19]
2
,3-bishydroxybenzoic acid.
Herein, we present
the oxidative coupling cyclization using commercial
available iron(II) phthalocyanine (FePc) as an
efficient catalyst via a radical type catalytic oxidation
reaction, allowing for the rapid access to complex
benzofuroindolenines (Figure 1).
During the past few decades, oxidative coupling
reactions had developed into an essential branch of
organic synthesis.[
1]
Diverse elegant methods
extensively complemented the fields of traditional
coupling reactions and provided widely applicable
approaches for new bond formation.[
2]
Treatment of THβC with 3,4-dihydroxybenzoic
acid in the presence of FePc (2.5 mol%) and t-
Efficient
oxidative coupling protocols for functionalized
indoles have been developed by the groups of
o
BuOOH (3 eq) at 0 C for 10 min afforded two easily
Harran,[
3]
[4]
[5]
[6]
separated products 1a and 1b in excellent yield (1a
and 1b are diastereomers with 43% + 43% isolated
yield, respectively). The significantly distinct NMR
data indicated that these novel structures are
Danishefsky,
Trost,
Nicolaou,
[7]
[8]
[9]
[10]
[11]
[15]
Overman, Muniz, MacMillan, Xiao,
Lei,
Vincent,[
12]
You,
[13]
Stephenson,
[14]
and others.
While, the synthetic utility of catalytic oxidative
coupling cyclization for construction of complex
benzofuroindolenines has not been fully developed.
[19]
completely different from our earlier report.
Through X-ray crystallographic analysis, we assigned
the chemical structures of these complex products as
benzofuroindolenines (Figure 2).
This interesting result encouraged us to test the
generality of catalytic oxidative coupling cyclization.
Various substrates were investigated to construct
valuable complex molecules. As shown in Figure 2,
we first investigated the reactions of a variety of
THβCs or THγCs with 3,4-dihydroxybenzoic acid.
The desired products were isolated in good to
excellent yields. Different N-substituted THβCs,
Figure 1. Recent work for the construction of fused
polycyclic indoles.
including Ts, Ac, SO
2
Me, SO Ph, COOMe, and
2
COOEt, afforded the desired products 2-7 in
satisfactory yields. Other THβCs or THγCs with
1
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Advanced Synthesis & Catalysis
10.1002/adsc.201801184
Figure 2. Scope of the catalytic oxidative coupling cyclization.
different substituents, such as F, Cl, Br, Me, OMe,
were well-tolerated, and the corresponding products
8
-19 were obtained in 67-96%. Notably, the reaction
was also suitable for tetrahydrocarbazoles. By using
various tetrahydrocarbazoles with different
substituents, the corresponding products 20-34 were
obtained in 55–99% yields. The structures of 16 and
2
7 were further established by X-ray crystallographic
[20]
analysis.
The extensive substrate scope and broad
functional-group compatibility of this transformation
encouraged us to further explore more catechols
derivatives
derivatives containing electron-withdrawing groups,
such as NO , CN, COOMe or COPh, were tolerable
(Figure
3).
3,4-Dihydroxyphenyl
2
to afford the corresponding products 35-49 in
moderate to excellent yields. The structure of 37 was
[20]
established by X-ray crystallographic analysis. It is
worth mentioning that compound 44 could be
performed on gram scale without a significant
deterioration in yield (98% versus 99%), indicating
the practical utility of this transformation in organic
synthesis.
Figure 3. Application of catalytic oxidative cyclization
coupling reaction.
2
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Advanced Synthesis & Catalysis
10.1002/adsc.201801184
In conclusion, we have developed an efficient
FePc-catalyzed oxidative coupling cyclization for
rapid construction of benzofuroindolenines in an
open flask. This protocol provides a library of
benzofuroindolenines which accessing undeveloped
chemical space for further structural modification.
The pharmacological characterizations of these
compounds will be outlined in due course.
Experimental Section
General Procedure for rapid construction of
benzofuroindolenines. To a solution of starting material
(
3
(
tetrahydrocarbazoles or THβCs or THγCs, 1.0 equiv) and
,4-dihydroxyphenyl derivatives (2.0 equiv) in CH CN
0.2 M) was added FePc (2.5 mol%), AcOH (2.0 equiv),
MsOH (0.1 equiv) and t‐ BuOOH (aq. 65%, 3.0 equiv) at
3
o
5
C. The reaction mixture was stirred at the same
temperature. After the reaction was completed (monitored
by TLC analysis), silica gel was added to the mixture and
then the solvent was removed in vacuo. The crude product
was purified by chromatography on silica gel to give the
desired product.
Figure 4. Mechanistic investigation of catalytic oxidative
coupling cyclization.
However, it is worth to mention that indoles fused
with five-membered ring or seven-membered ring
and catechols with electron-donating substituents
were not well-tolerated, and the products were
obtained in extremely low yields.
Acknowledgements
This work was supported by Joint research project of health and
education of Fujian Province (No. WKJ2016-2-06) and the
National Natural Science Foundation of China (No. 81571802).
To further demonstrate the value of this general
strategy, we focused on the desired pharmaceutically
drug-likeness molecules. N-Ac-adrenalone as one of References
the catecholics with extensive pharmacological
properties can be successfully functionalized to
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Advanced Synthesis & Catalysis
10.1002/adsc.201801184
COMMUNICATION
Catalytic Oxidative Coupling Cyclization for
Construction of Benzofuroindolenines under Mild
Reaction Conditions
Adv. Synth. Catal. Year, Volume, Page – Page
Catalytic oxidative coupling cyclization for rapid
construction of benzofuroindolenines was
described.
a,†
a,†
a
Yuqi Lin, Jinxiang Ye, Wenting Zhang Yu
a
a,
Gao, and Haijun Chen *
6
This article is protected by copyright. All rights reserved.