Rh(III)-catalyzed [4?+?1]-annulation of azobenzenes with α- carbonyl sulfoxonium ylides toward 3-acyl-(2H)-indazoles

Article abstract of DOI:10.1016/j.tetlet.2018.05.001

A Rh(III)-catalyzed [4 + 1]-annulation of azobenzenes with α- carbonyl sulfoxonium ylides was developed to access 2H-indazoles in moderate to excellent yields with good functional group compatibilities. It proceeded with the sequential insertion of the Rh(III) carbene to the C?H bond and cyclization steps, where sulfoxonium ylides served as efficient and stable carbene precursor.

Full text of DOI:10.1016/j.tetlet.2018.05.001

Accepted Manuscript
Rh(III)-Catalyzed [4 + 1]-Annulation of Azobenzenes with α- Carbonyl Sul-
foxonium Ylides toward 3-Acyl-(2H)-Indazoles
Jiawei Zhu, Song Sun, Jiang Cheng
PII:
S0040-4039(18)30582-3
https://doi.org/10.1016/j.tetlet.2018.05.001
TETL 49948
DOI:
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
21 March 2018
22 April 2018
2 May 2018
Please cite this article as: Zhu, J., Sun, S., Cheng, J., Rh(III)-Catalyzed [4 + 1]-Annulation of Azobenzenes with
α- Carbonyl Sulfoxonium Ylides toward 3-Acyl-(2H)-Indazoles, Tetrahedron Letters (2018), doi: https://doi.org/
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0.1016/j.tetlet.2018.05.001
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Rh(III)-Catalyzed [4 + 1]-Annulation of
Azobenzenes with α- Carbonyl Sulfoxonium Ylides toward 3-Acyl-(2H)-Indazoles
Jiawei Zhu, Song Sun, and Jiang Cheng*

1
Tetrahedron Letters
jo u r n a l h o m e p a g e : w w w . e ls e v ie r . c o m
Rh(III)-Catalyzed [4 + 1]-Annulation of Azobenzenes with α- Carbonyl Sulfoxonium
Ylides toward 3-Acyl-(2H)-Indazoles
Jiawei Zhu, Song Sun and Jiang Cheng*
a
School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Jiangsu Province Key Laboratory of
Fine Petrochemical Engineering, Changzhou University, Changzhou, 213164, P. R. China.
b
College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325000, P. R. China.
†
E-mail: jiangcheng@cczu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A Rh(III)-catalyzed [4 + 1]-annulation of azobenzenes with α- carbonyl sulfoxonium ylides
was developed to access 2H-indazoles in moderate to excellent yields with good functional
group compatibilities. It proceeded with the sequential insertion of the Rh(III) carbene to
the C−H bond and cyclization steps, where sulfoxonium ylides served as efficient and
stable carbene precursor.
Available online
Keywords:
Rhodium-catalyzed
sulfoxonium ylides
2
H-indazoles
The indazole backbone is ubiquitous in natural products,
regard, In the case of 2H-indazole, Lee developed a palladium-
catalyzed [4 1]-annulation of 2-iodoazoarenes with
acyldiazoacetates to access 2H-indazoles (Scheme 1a).
1
drugs, agrochemicals, and bioactive compounds. Therefore,
numerous efforts have been developed to construct these
biologically important skeletal motifs due to their potential
+
1
3
Afterwards, You reported the Rh(III)-Catalyzed [4 + 1]-
2
pharmaceutical properties (Figure 1). However, compared with
annulation of azoxy compounds with diazoesters to access 2H-
3
5b
the well-developed methodologies toward 1H-indazoles, only a
indazoles (Scheme 1b). However, these reactions are mostly
limited number of approaches were demonstrated to access 2H-
limited to functionalized azobenzenes (halogenated or
azoxylated) and acceptor diazo compounds; while simple
diazoacetates or diazoketones failed to work.
4,5
6
indazoles, especially 3-acyl-2H-indazoles. Thus, it is attractive
and highly desirable to develop straightforward and atom-
economic pathways toward 3-acyl-2H-indazoles in organic
chemistry.
Scheme 1. Transition-Metal-Catalyzed [4+1] Annulation of
Carbene Precursors toward 2H-Indazoles
Figure 1. Selected Bioactive 2H-Indazoles.
Transition-metal-catalyzed sequential directing group-
assisted C−H bond activation/cyclization represents a powerful
7
approach for the construction of heterocycles. Significant
8
9
10
progress have been made by Glorius, Ackermann, Wang,
1
1
12
Chang, and others. α-Diazocarbonyl compounds have been
extensively considered as metal-carbene precursors to insert into
C−H bonds followed annulation toward heterocycles. With this
Thus, it is urgent to develop efficient and stable surrogate of
1
4
diazo compounds to overcome these limitations. Sulfur ylides
function as surrogates of diazo compounds in metal-catalyzed

Tetrahedron
4
reactions due to the relatively higher security and stability.
Recently, Aissa and co-workers pioneered a rhodium-catalyzed
slightly influenced the reaction, as 3ia was isolated in 63%
yields. In the case of the meta- substituted substrate, the
cyclization selectively took place in the ortho- position of phenyl
with less hindrance (3ca). Unfortunately, the 4-nitro analogue 1j
failed to work (3ja, 0%). Notably, the practicability of this
transformation was further increased as 3aa was isolated in an
acceptable 78% yield in a 3 mmol scale reaction (for details, see
the Supporting Information).
2
15a
coupling of aromatic C(sp )−H with α-aroyl sulfur ylides.
Afterward, Li applied this strategy in the synthesis of a variety of
1
5b
carbocycles and N-heterocycles. Herein, we wish to report a
Rh(III)-Catalyzed [4 + 1] annulation proceeded with the
sequential insertion of the C−H bond to the Rh(III) carbenes
1
5,16
derived from sulfoxonium ylides,
reductive elimination and
cyclization steps towards 3-acyl-(2H)-indazoles (Scheme 1c).
a
Scheme 2. The Scope of Azobenzenes.
Table 1. Selected Results for Screening the Optimized
a
Reaction Conditions.
b
entry
[Ag]
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
additive
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
AcOH
solvent
MeOH
THF
yield (%)
43
1
2
3
4
5
6
7
8
9
6
6
< 5
15
6
DMSO
Dioxane
MeCN
DCE
6
< 5
25
6
6
55
6
DCE
63
c
d
e
f
AgSbF
6
Cu(OAc)
Cu(OAc)
Cu(OAc)
--
2
2
2
DCE
83 , 47 , 65 ,73
AgOAc
DCE
33
< 5
20
1
1
1
0
1
2
Ag
AgSbF
--
2
O
DCE
6
DCE
g
Cu(OAc)
2
DCE
< 5
a
Reaction conditions: Azobenzene 1a (0.2 mmol), sulfoxonium ylide 2a (0.4
mmol), [Cp*RhCl (4 mol %), [Ag] (16 mol %), additive (30 mol %), in
DCE (2 mL), under air, 100 C, 24 h. Isolated yield. Under air. Under N
2 2
]
o
b
c
d
2
.
e
o
f
o
g
2 2 6
At 80 C. At 120 C. without [Cp*RhCl ] or AgSbF .
Initially, we tested the reaction of azobenzene 1a (0.2 mmol),
and sulfoxonium ylide 2a (0.4 mmol) in the presence of
[
%
Cp*RhCl ] (4 mol %), AgSbF (16 mol %) and NaOAc (30 mol
) in MeOH (2 mL) under air at 100 C for 24 h. To our delight,
2
2
6
o
the product 3-acyl-(2H)-indazole 3aa was isolated in 43% yield
Table 1, entry 1). During the screening of solvents, DCE was
a
(
Reaction conditions: Azobenzene 1a (0.2 mmol), sulfoxonium ylide 2a (0.4
superior to THF (< 5%), DMSO (15%), 1,4-dioxane (< 5%), and
MeCN (25%, entries 1−6). Notably, the yield increased to 63%
and 83% by using AcOH and Cu(OAc)2 as the additives,
mmol), [Cp*RhCl
2 2 6 2
] (4 mol %), AgSbF (16 mol %), Cu(OAc) (30.0 mol
o
%), in DCE (2 mL), under air, 100 C, 24 h.
respectively (entries 7 and 8). Besides, varying either the N
atmosphere or reaction temperature (80 and 120 C) all decreased
In this case of unsymmetrical azobenzenes, such as (E)-1-
phenyl-2-(o-tolyl)diazene and (E)-1-(2-methoxyphenyl)-2-
2
o
the reaction efficiency (Table 1, entry 8). Other silver additives
such as AgOAc (33%) and Ag O (< 5%) were inferior to AgSbF
phenyldiazene, it was the electron nature but not the hindrance in
the phenyl controlled the selectivity. The reaction selectively
took place in the electron-rich aryl ring substituted with electron-
donating group, providing 3ka (72%) and 3la (78%) in good
yields, respectively. Moreover, unsymmetrical azobenzene 1m
was also compatible to afford a mixture of 3- acyl (2H)-indazoles
2
6
(entries 9 and 10). The product 3aa was isolated in 20% yield in
the absence Cu(OAc) (entry 11). Finally, the blank reaction
2
revealed no reaction took place at all in the absence of either
[
Cp*RhCl ] or AgSbF (entry 12).
2 2 6
3
ma and 3mb in 49% combined yield with a 1.3:1 ratio.
To evaluate the scope and limitation of this process, the
a
reactivity of various azobenzene derivatives was investigated, as
shown in Scheme 2. As expected, both substituted azobenzenes
worked well with good to excellent yields. When methyl and
methoxy- substituted azobenzenes were treated with 2a under the
standard conditions, the corresponding products (3ba-fa, 50-
Scheme 3. The Scope of α- Carbonyl Sulfoxonium Ylides
8
5%) were isolated in moderate to good yields. Azobenzenes
bearing halogen groups on the phenyl ring ran smoothly under
the standard procedure with moderate to excellent yields. For
example, 4-chloro-substituted azobenzene 1g provided the 2H-
indazole 3ga in 92% yield. The sterically hindered substituents

3
a
Reaction conditions: Substituted azobenzene 1a (0.2 mmol),
sulfoxonium ylide 2 (0.4 mmol), [Cp*RhCl (4 mol %), AgSbF (16 mol
), Cu(OAc) (30 mol %), in DCE (2 mL), under air, 100 C, 24 h.
2
]
2
6
o
%
2
Meanwhile, the scope of α- carbonyl sulfoxonium ylides was
Scheme 5. A Tentative Mechanism.
studied, as shown in Scheme 3. Sulfoxonium ylides bearing both
electron-donating groups (3ab-af, 65-81%) and electron-
withdrawing groups (3ag, 63%; 3ah, 67%) all coupled smoothly
with azobenzene in moderate to good yields under the standard
conditions. Furthermore, alkyl- and heteroaryl-substituted
analogues also worked well under the standard conditions,
leading to corresponding 3-acyl-(2H)-indazoles derivatives in
In conclusion, we have disclosed Rh(III)-Catalyzed [4 + 1]-
annulation of substituted azobenzenes with α- carbonyl
sulfoxonium ylides leading to a wide range of of 3-acyl 2H-
indazoles, which are crucial motifs of biologically active
compounds. It represents a novel and efficient method to access
such frameworks from simple starting material.
7
2% (3ai), 75% (3aj) and 48% (3ak) yields, respectively.
Acknowledgments
We thank the National Natural Science Foundation of China
(nos. 21572025, and 21602019), “Innovation & Entrepreneurship
Talents” Introduction Plan of Jiangsu Province, Natural Science
Foundation of Jiangsu Province (BK20171193), the Key
University Science Research Project of Jiangsu Province
(
15KJA150001), Jiangsu Key Laboratory of Advanced Catalytic
Scheme 4. KIE Study.
Materials & Technology (BM2012110) and Advanced Catalysis
and Green Manufacturing Collaborative Innovation Center for
financial supports. Sun thanks Young Natural Science
Foundation of Jiangsu Province (BK20150263) for financial
supports.
Next, more experiments were conducted to get insight into the
reaction mechanism (Scheme 4). The inter-molecular kinetical
isotope effect (KIE) was found to be 2.1. Thus, the ortho- C−H
bond cleavage of azobenzene might be involved in the rate-
determining step.
Based on these experimental results (Scheme 4) and reported
3
g, 9a
literature,
a proposed mechanism as shown in Scheme 5.
References and notes
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undergoes α- elimination of DMSO gives a reactive carbene
species C. Afterward, migratory insertion would deliver a six-
(
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5
1
2
3
. Annulation of azobenzenes with α- carbonyl
sulfoxonium ylides
. Features with excellent yields and good functional
group compatibilities.
. Sulfoxonium ylides served as efficient and stable
carbene precursor