Rhodium(III)-catalyzed direct C-7 sulfonamidation and amination of indolines with arylsulfonamides and trifluoroacetamide

Article abstract of DOI:10.1016/j.tetlet.2019.03.069

A rhodium-catalyzed direct C–H sulfonamidation and amidation of C-7 position of indolines by simple and commercially available arylsulfonamides and trifluoroacetamide has been developed, affording a series of N-arylsulfonamides and N-aryltrifluoroacetamides in moderate to excellent yields, respectively. Notably, this catalytic system is highly convenient on mmol scale.

Full text of DOI:10.1016/j.tetlet.2019.03.069

Accepted Manuscript
Rhodium(III)-catalyzed direct C-7 sulfonamidation and amination of indolines
with arylsulfonamides and trifluoroacetamide
Yaqun Dong, Song Sun, Jin-tao Yu, Jiang Cheng
PII:
S0040-4039(19)30307-7
https://doi.org/10.1016/j.tetlet.2019.03.069
TETL 50710
DOI:
Reference:
Tetrahedron Letters
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Revised Date:
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15 March 2019
29 March 2019
Please cite this article as: Dong, Y., Sun, S., Yu, J-t., Cheng, J., Rhodium(III)-catalyzed direct C-7 sulfonamidation
and amination of indolines with arylsulfonamides and trifluoroacetamide, Tetrahedron Letters (2019), doi: https://
doi.org/10.1016/j.tetlet.2019.03.069
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Rhodium(III)-catalyzed direct C-7
sulfonamidation and amidation of indolines with
arylsulfonamides and trifluoroacetamide
Yaqun Dong, Song Sun*, Jin-tao Yu and Jiang Cheng

1
Tetrahedron Letters
Rhodium(III)-catalyzed direct C-7 sulfonamidation and amination of indolines with
arylsulfonamides and trifluoroacetamide
Yaqun Dong, Song Sun,* Jin-tao Yu and Jiang Cheng
aSchool 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.
†E-mail: sunsong@cczu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A rhodium-catalyzed direct C−H sulfonamidation and amidation of C-7 position of
indolines by simple and commercially available arylsulfonamides and trifluoroacetamide
has been developed, affording
a
series of N-arylsulfonamides and N-
aryltrifluoroacetamides in moderate to excellent yields, respectively. Notably, this catalytic
system is highly convenient on mmol scale.
Available online
Keywords:
Rhodium-catalyzed
Indolines
N-arylsulfonamides
C−H amidation
Being important structural motif, N-arylsulfonamides and
their derivatives widely exist in pharmaceuticals with
diverse biological activities, such as anticancer,
antibacterial, anticonvulsant, and HIV protease inhibitory
activities.1 Traditionally, base-promoted nucleophilic
substitution of sulfonyl chloride with an aromatic amine
of C-7 position of indolines.9 For example, Zhu reported
Ru(II)-catalyzed amidation using sulphonyl azides.10a
Afterward, Chang developed Ir(III)-catalyzed amidation of
indoline by sulphonyl azide.11 Zhou and Li demonstrated
Ir(III)-catalyzed amidation of indoline using tosyl, alkyl, and
acyl azides (Scheme 1, eq. 3, path a).12 However, despite
much progress has been made in this field, the development
of more practical and mild procedures to generate C-7
amidated indolines remains an area of synthetic interest.
Herein, we describe a rhodium catalyzed direct C-H
sulfonamidation and amidation of C-7 position of indolines
with commercially available arylsulfonamides and
trifluoroacetamide toward a series of C7- amidated indolines
in moderate to high yields. (Scheme 1, eq. 3, path b).
represents
a straightforward method to access these
compounds, albeit resulting in stoichiometric inorganic
waste (Scheme 1, eq. 1).2 Alternatively, transition metal-
catalyzed cross-coupling of sulfonamides with either aryl
halides or arylboronic acids, such as palladium-catalyzed
Buchwald–Hartwig aminations3 and copper-catalyzed
Chan−Lam coupling reactions4was powerful method to
generate N-arylsulfonamides (Scheme 1 eq. 2). Very
recently, Macmillan and co-workers reported an elegant
example of visible light induced nickel-catalyzed
sulfonamidation of aryl and heteroaryl halides toward a
Scheme 1. Synthetic pathway to access N-arylsulfonamides
series
of
N-arylsulfonamides.5
However,
prefunctionalization is required in these reactions.
Undoubtedly, the direct amination/amidation of C-H bonds
represents a straightforward and promising approach, which
obviates the pre-functionalization of substrates.6
On the other hand, the indoles and indolines are
ubiquitous structural motifs found in many natural products
with diverse and important biological activities. The direct
C7-functionalization of indolines through C-H activation has
been investigated by several groups.7 Among which, the C7-
amidated indolines are of great value in drug discovery
owing to their potent and diverse biological activities.8
However, limited work has been reported in the amidation
Initially, we tested the reaction of 1-(indolin-1-yl)ethanone
1a) and 4-methylbenzenesulfonamide (2a) in DCE under 100
(

Tetrahedron
4
oC in the presence of [Cp*RhCl2]2 (5 mol %), AgOTf (20 mol %)
and PhI(OAc)2 (1 equiv.). As expected, the desired product 3a
95% and 91% yield, respectively. Moreover, N-pivaloyl, and N-
1-propionyl indolines were readily amidated under the present
conditions (3n and 3o). To our delight, this procedure was
applicable to a 1 mmol scale reaction, providing 3a in 68% yield.
(
)
was isolated in 37% yield (Table 1, entry 1). To our delight, the
yield dramatically increased to 86% with the assistance of
additional of AgOAc (20 mol %, Table 1, entry 2), which would
facilitate the C-H activation step.13 Other additives such as
PivOH, LiOAc, NaOAc and HOAc increased the reaction
efficiency to some extents; while the yield increased into 93% in
the presence of 3 equivalent of HOAc14 (Table 1, entries 3-6).
Among the solvents tested, DCE was the best choice (Table 1,
entries 6-9). Under the control experiments, this reaction did not
work or resulted in low efficiency in the absence of each reaction
parameters (Table 1, entries 10-11). Additionally, other Ag salts
such as AgSbF6 did not promote this reaction at all (Table 1,
entry 12). The reaction efficiency was decreased when the
amount of silver salts was reduced (Table 1, entry 13).
Subsequently, the scope and limitation of arylsulfonamides
were also tested. Generally, except the 4-CN substituted analogue
(3t, 35%), the reaction efficiency was not sensitive to the
electronic property of the groups on the phenyl ring of
arylsulfonamides, as substrates bearing both electron-donating
(3p-3q, 72-79%) and electron-withdrawing groups (3r-3s, 80-
90%) worked well to deliver the desired products in good yields.
Table 1. Selected results for screening the optimized reaction
conditions.a
yieldb
(%)
entry
Ag salts
additive
solvent
1
2
AgOTf
DCE
DCE
37
86
AgOTf/AgOAc
AgOTf/AgOAc
AgOTf/AgOAc
AgOTf/AgOAc
AgOTf/AgOAc
AgOTf/AgOAc
AgOTf/AgOAc
AgOTf/AgOAc
AgOTf/AgOAc
AgOAc
3
PivOH
LiOAc
NaOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
DCM
DCE
83
4
33
5
DCM
DCE
26
6
93
7
DCM
THF
84
8
85
9
diglyme
DCE
75
10c
11
12
13d
N.R.
12
DCE
AgSbF6
DCE
N.R.
49
AgOTf/AgOAc
DCE
a Reaction conditions: 1-(indolin-1-yl)ethanone 1a (0.15 mmol), 4-
methylbenzenesulfonamide 2a (0.3 mmol), [Cp*RhCl2]2 (5 mol %),
Ag salts (20 mol %), PhI(OAc)2o (1 equiv.), additive (3 equiv.),
solvent (1.5 mL) under N2 at 100 C for 16 h, in a sealed Schlenk
Figure 1. Substrates scope N-acetyl indolines and arylsulfonamides.
Reaction conditions: 1 (0.15 mmol), 2 (0.3 mmol), [Cp*RhCl2]2 (5 mol %),
AgOTf (20 mol %), AgOAc (20 mol %), PhI(OAc)2 (1 equiv.), HOAc (3
equiv.), DCE (1.5 mL) under N2 at 100 oC for 16 h, in a sealed Schlenk tube,
unless otherwise noted. a 1 mmol scale reaction.
c
tube, unless otherwise noted. b Isolated yield. Without [Cp*RhCl2]2
or PhI(OAc)2. d10 mol% AgOTf, 10 mol% AgOAc.
To our delight, as shown in Figure 2, trifluoroacetamide
reacted readily with a series of C2 and C5-substitued
indolines to deliver the desired products 4a-4d in moderate
to good yields.
With the optimized reaction conditions in hand, the scope and
limitation of substrates were evaluated, as shown in Figure 1.
This procedure was applicable for C2, C3, C4, C5, and even C6-
substituted N-acetyl indolines (3a-3m). Generally, the reaction
tolerated both electron-donating and electron-withdrawing
groups. However, the substrates bearing electron-withdrawing
groups gave poorer results than those bearing electron-donating
groups. For example, methyl, methoxyl substituted N-acetyl
indolines afforded the products 3b-3h in nearly quantitative
yields. However, the analogues bearing electron-withdrawing
groups provided the sulfonamidation product 3j-3m in only 41%-
58% yields. Notably, some functional groups, such as, fluoro,
chloro, bromo, methoxycarbonyl groups, which were suitable for
potentially further functionalization, survived well in these
reactions (3j-3m). Additionally, poly-substituted indolines with
substitution either at C2 or C3 also ran smoothly under the
standard conditions to generate the desired products 3d and 3e in
Figure 2.The C-7 amination of indolines with trifluoroacetamide. Reaction
conditions:
1-(indolin-1-yl)ethanone
1
(0.15
mmol),
2,2,2-
trifluoroacetamide (0.3 mmol), [Cp*RhCl2]2 (5 mol %), AgOTf (20 mol %),

3
AgOAc (20 mol %), PhI(OAc)2 (1 equiv.), HOAc (3 equiv.), DCE (1.5 mL)
under N2 at 100 oC for 16 h, in a sealed Schlenk tube, unless otherwise noted.
Some control experiments were conducted to get some insights
as the amino source, affording a series of N-arylsulfonamides
and N-aryltrifluoroacetamides. This catalytic system is highly
convenient on mmol scale. The desired products feature diverse
functional group tolerance with good to excellent yields.
into this transformation. Firstly, N-acetylindoline (1a) was
treated by 10 equiv of D2O under the standard conditions. This
reaction led to 80% deuterium incorporation at the C7 position of
D-1a (Scheme 2 eq. 1). This deuterium exchange experiment
indicated that the C−H activation step was reversible. An
intermolecular competition experiment with isotopically labeled
1a' was conducted (see supporting information). A kinetic
isotope effect (KIE) of kH/kD = 3.3 suggested that the C−H
cleavage might be involved in the rate determining step. (Scheme
2, eq. 2)
Acknowledgments
We thank the National Natural Science Foundation of China
(nos. 21602019 and 21572025), “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
Materials & Technology (BM2012110) and Advanced Catalysis
and Green Manufacturing Collaborative Innovation Center for
financial supports.
Scheme 2. Mechanistic study
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5
1. Rhodium-catalyzed direct C-7 sulfonamidation and
amination of indolines
2. Simple arylsulfonamides and trifluoroacetamide
used as amide source
3. Catalytic system is highly convenient on mmol
scale.