Copper-Catalyzed Arylsulfonylation and Cyclizative Carbonation of N-(Arylsulfonyl)acrylamides Involving Desulfonative Arrangement toward Sulfonated Oxindoles

Article abstract of DOI:10.1021/acs.orglett.7b02827

Sulfonated oxindoles are accessed by a Cu(OAc)₂-catalyzed three-component reaction of N-(arylsulfonyl)acrylamides, DABSO, and aryldiazonium tetrafluoroborates. This transformation is triggered by the formation of arylsulfonyl radicals in situ from the reaction of aryldiazonium tetrafluoroborates and DABSO. Afterward, the sequential radical addition, radical cyclization, and desulfonylative 1,4-aryl migration take place to provide the final product by the formation of four new bonds in one pot. This procedure shows good functional group tolerance.

Full text of DOI:10.1021/acs.orglett.7b02827

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
Copper-Catalyzed Arylsulfonylation and Cyclizative Carbonation of
N‑(Arylsulfonyl)acrylamides Involving Desulfonative Arrangement
toward Sulfonated Oxindoles
Hepan Wang, Song Sun, and Jiang Cheng*
School of Petrochemical Engineering, and Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Changzhou
University, Changzhou 213164, P. R. China
S
* Supporting Information
ABSTRACT: Sulfonated oxindoles are accessed by a Cu(OAc)2-catalyzed three-component reaction of N-(arylsulfonyl)-
acrylamides, DABSO, and aryldiazonium tetrafluoroborates. This transformation is triggered by the formation of arylsulfonyl
radicals in situ from the reaction of aryldiazonium tetrafluoroborates and DABSO. Afterward, the sequential radical addition,
radical cyclization, and desulfonylative 1,4-aryl migration take place to provide the final product by the formation of four new
bonds in one pot. This procedure shows good functional group tolerance.
cyclizative carbonation of N-(arylsulfonyl)acrylamide may
xindoles and their derivatives represent a class of
Oimportant N-heterocycles possessing advanced pharma- provide a facile pathway toward sulfonated oxindoles. Notably,
ceutical and biologic activities.1 Recently, the difunctionaliza-
sulfones are ubiquitous in pharmaceuticals, agrochemicals, and
materials.5 Sulfonyl radicals were derived from corresponding
tion of N-(arylsulfonyl)acrylamide has been widely developed
sulfonyl halides, sulfonyl selenides, sulfonyl azides, sulfonyl
cyanides (Scheme 1b, eq 2),6 sulfinates,7 sulfinic acids,8 and
sulfonyl hydrazides9 (Scheme 1, eq 3). From the synthesis
point of view, the formation of sulfonyl radicals derived from
two components would be beneficial to the diversity of these
species. Wu pioneered the application of sulfonyl radicals
derived from DABSO and aryldiazonium in organic synthesis.10
Herein, we wish to report a copper(II) acetate-catalyzed three-
component reaction of N-(arylsulfonyl)acrylamides, DABSO,
and aryldiazonium tetrafluoroborates, leading to sulfonated
oxindoles.
in the synthesis of functionalized oxindoles, whereby the
carbonation and other functionalization of vinyl proceeds with
sequential addition of radical to alkenyl, radical 1,4-aryl
migrations by ipso cyclization, and desulfonylation (Scheme
1a, eq 1).2 For instance, trifluoromethyl,3a−d phosphonyl,3e and
azidinyl3f oxindoles were efficiently accessed, which were
applied in anticholinergic drugs, insecticides, herbicides, and
versatile intermediates.4 With this strategy, triggered by the
addition of sulfonyl radicals to vinyl, the arylsulfonylation and
Scheme 1. Radical Reactions of N-(Arylsulfonyl)acrylamide
We began our investigation with the reaction of N-methyl-N-
tosylmethacrylamide 1a, phenyldiazonium tetrafluoroborate 2a,
and DABSO in HOAc at 60 °C. After 12 h, the 1,3,6-trimethyl-
3-((phenylsulfonyl)methyl)indolin-2-one 3a was isolated in
48% yield (Table 1, entry 1). The yield dramatically increased
to 62% (60 °C) and 72% (80 °C) in the presence of copper(II)
acetate (10 mol %, Table 1, entry 2). Other solvents, such as
ethanol (52%), DCM (50%), DCE (48%), 1,4-dioxane (43%),
toluene (trace), MeCN (trace), and DMF (trace) were inferior
to HOAc (Table 1, entries 3−10). Replacing Cu(OAc)2 with
Cu(OTf)2 decreased the reaction efficiency (51%, Table 1,
entry 11). Among the catalysts tested, such as CuCl2 (42%),
CuBr2 (53%), Cu2O (61%), CuS (50%), and CuBr (42%), an
Cu(OAC)2 were the best (Table 1, entries 12−16). The
and Generation of Sulfonyl Radicals
Received: September 10, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02827
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Selected Results for Screening the Optimized
a
Reaction Conditions
entry
cat.
sol.
temp
yield (%)
1
HOAc
HOAc
EtOH
DCM
60
60
60
60
60
60
60
60
60
80
80
80
80
80
80
80
48
62
52
50
48
43
2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OTf)2
CuCl2
3
4
5
DCE
6
dioxane
toluene
MeCN
DMF
7
trace
trace
trace
8
9
b
c d
10
11
12
13
14
15
16
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
72/62 /37 /0
51
42
53
61
50
42
Figure 1. Substrates scope of aryldiazonium tetrafluoroborate.
Reaction conditions: N-Ts acrylamide 1a (0.1 mmol), aryldiazonium
tetrafluoroborate 2 (0.15 mmol), DABSO (0.1 mmol), Cu(OAc)2 (10
mol %), HOAc (1.0 mL), at 80 °C under N2 for 12 h, in a sealed
Schlenk tube.
CuBr2
Cu2O
CuS
CuBr
a
Reaction conditions: 1a (0.1 mol), 2a (0.15 mmol), DABSO (0.1
mmol), Cu(OAc)2 (10 mol %), solvent (1.0 mL), under N2 for 12 h,
b
c
d
isolated yields. Under air. DABSO (0.05 mmol). DABSO (5 mol
%): DABCO = 1,4-diazabicyclo[2.2.2]octane-1,4-diium-1,4-disulfinate.
reaction became retarded under air (62%, Table 1, entry 10).
Changing the loading of DABSO (0.05 mmol) decreased the
yields, while it did not work in the catalytic amount of DABSO
(5 mol %, Table 1, entry 10). The practicality of this procedure
was increased since this reaction was applicable in a 1 mmol
scale to provide 3a in an acceptable 64% isolated yield.
With the optimized catalytic system in hand, the scope of
aryldiazonium in this three-component reaction was studied, as
shown in Figure 1. As expected, the reaction efficiency was not
sensitive to the electronic property of the phenyl ring of
aryldiazonium tetrafluoroborates as substrates bearing both
electron-donating (3b−f, 53−78%) and electron-withdrawing
groups (3g−j, 66−77%) all ran smoothly under the standard
procedure. The halo groups survived well after the reaction
(3g−i). Unfortunately, the attempt to access 1,3,6-trimethyl-3-
((pyridin-3-ylsulfonyl)methyl)indolin-2-one failed.
Figure 2. Substrates scope of N-(arylsulfonyl)acrylamide. Reaction
conditions: N-(arylsulfonyl)acrylamide 1 (0.1 mmol), phenyldiazo-
nium tetrafluoroborate 2a (0.15 mmol), DABSO (0.1 mmol),
Cu(OAc)2 (10 mol %), HOAc (1.0 mL), at 80 °C under N2 for 12
h, in a sealed Schlenk tube.
Next, the scope of N-(arylsulfonyl)acrylamide was studied, as
shown in Figure 2. Once again, the reaction efficiency was not
sensitive to the electronic property of the groups on the phenyl
ring of N-(arylsulfonyl)acrylamide as substrates bearing both
electron-donating groups (3p, 69%) and electron-withdrawing
groups (3m−o, 56−67%; 3q, 55%; 3r, 54%) worked well with
moderate to good yields. Pleasingly, the functional groups, such
as fluoro (3m, 67%), chloro (3n, 56%), and bromo (3o, 61%)
tolerated well under the standard conditions, providing facile
handles for potentially further functionalizations. Interestingly,
the substrate with a phenyl adjacent to the carbonyl of the
acrylamide moiety (phenyl, 3t, 58%) showed reactivity under
the procedure. However, the ethyl analogue resulted in
complex mixtures. Notably, the naphthalene groups and N-
heteroaryl analogues worked well with moderate yields, such
that 3l and 3s were isolated in 59% and 42% yields.
2.0 equiv of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)
were added to the standard reaction, indicating the involvement
of a radical pathway (Scheme 2, eq 1). Moreover, in a control
experiment by employing DABSO (5 mol %) in the reaction of
N-methyl-N-tosylmethacrylamide 1a with phenyldiazonium
Scheme 2. Preliminary Mechanism Study
More experiments were conducted to get some insights into
this transformation. This transformation was terminated when
B
DOI: 10.1021/acs.orglett.7b02827
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Notes
tetrafluoroborate 2a under the conditions (Scheme 2 eq 2), no
free sulfur dioxide (SO2) gas was detected (see the Supporting
Information for details), which indicated the important role of
the tertiary amine in DABCO.
Based on the aforementioned experimental observations and
previous reports,10,11 a plausible mechanism was proposed
(Scheme 3). The arydiazonium cation 2 would combine with
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(nos. 21272028 and 21572025), “Innovation & Entrepreneur-
ship Talents” Introduction Plan of Jiangsu Province, 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 support. S.S. thanks the National Natural
Science Foundation of China (no. 21602019) and Young
Natural Science Foundation of Jiangsu Province (BK20150263)
for financial support.
Scheme 3. Proposed Mechanism
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b02827.
Experimental procedures and spectra (PDF)
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: jiangcheng@cczu.edu.cn.
ORCID
Song Sun: 0000-0002-9974-6456
Jiang Cheng: 0000-0003-2580-1616
C
DOI: 10.1021/acs.orglett.7b02827
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DOI: 10.1021/acs.orglett.7b02827
Org. Lett. XXXX, XXX, XXX−XXX