α-Amino Acid Sulfonamides as Versatile Sulfonylation Reagents: Silver-Catalyzed Synthesis of Coumarins and Oxindoles by Radical Cyclization

Article abstract of DOI:10.1002/ejoc.201800901

We developed a silver-catalyzed strategy for the generation of sulfonyl radicals from sulfonamides derived from α-amino acids. The reaction proceeded via a decarboxylation, N–S bond cleavage and radical cyclization sequence and allows the difunctionalization of alkynes and the synthesis of 3-sulfonylated coumarins. The reaction tolerated a broad scope of substrates and functional groups and could be extended to the synthesis of oxindoles and an isoquinolinedione by the capturing of the sulfonyl radical with an alkene moiety. Moreover, the proposed mechanism was supported experimentally and by DFT calculations.

Full text of DOI:10.1002/ejoc.201800901

A Journal of
Accepted Article
Title: α-Amino Acid Sulfonamides as Versatile Sulfonylation Reagents:
Silver-Catalyzed Synthesis of Coumarins and Oxindoles by
Radical Cyclization
Authors: Kyalo Stephen Kanyiva, Daisuke Hamada, Sohei Makino,
Hideaki Takano, and Takanori Shibata
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800901
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800901
Supported by

10.1002/ejoc.201800901
European Journal of Organic Chemistry
COMMUNICATION
α-Amino Acid Sulfonamides as Versatile Sulfonylation Reagents:
Silver-Catalyzed Synthesis of Coumarins and Oxindoles by
Radical Cyclization
Kyalo Stephen Kanyiva,*[a] Daisuke Hamada,[b] Sohei Makino,[b] Hideaki Takano,[b] and Takanori
Shibata,*[b]
Abstract: We developed a silver-catalyzed strategy for the
generation of sulfonyl radicals from sulfonamides derived from
α-amino acids. The reaction proceeded via a decarboxylation, N-
S bond cleavage and radical cyclization sequence and allows
the difunctionalization of alkynes and the synthesis of 3-
sulfonylated coumarins. The reaction tolerated a broad scope of
substrates and functional groups and could be extended to the
synthesis of oxindoles and an isoquinolinedione by the capturing
of the sulfonyl radical with an alkene moiety. Moreover, the
proposed mechanism was supported experimentally and by DFT
calculations.
alkenes has emerged as
a
powerful method for the
regioselective synthesis of sulfones.[4d,7-13] Commonly used
sources of sulfonyl radicals include sulfinates[8] and sulfonyl
hydrazides,[9] whereby metal catalysts and/or stoichiometric
oxidants are used (Figure 1). Sulfonic and sulfinic acids,10
arylsulfonyl chlorides[11] and tosyl cyanides12 have also been
utilized. Reactions of DABCOŸSO2 with aryl diazosalts were
recently also used to access sulfonyl radicals.[4d,13] Despite this
progress, reagents such as sulfonic acids and sulfinic acids are
often unstable to handle, sulfonyl hydrazides require toxic
hydrazines for preparation, aryl diazosalts are sometimes
explosive, sulfonyl chlorides are sensitive to water, while sulfonyl
cyanides are expensive and also sensitive to water. In addition,
limited substrate scope and need for harsh conditions in some of
the reported sulfonylation reactions inspire the development of
alternative methods to access sulfonyl radicals.
The introduction of a sulfonyl group into an organic compound
changes the physical and chemical properties of the parent
molecule. Therefore, organosulfones are common in functional
materials, medicines and agrochemicals.[1] For instance, drugs
such as dapsone (leprosy), tazobactam (antibiotic) and CX157
(antidepressant) contain a sulfone functionality. In addition,
RSO2Na
RSO2NHNH2
RSO3H, RSO2H
(ref. 9)
(ref. 8)
(ref. 10)
sulfones also participate in
a wide range of synthetic
transformations, making them versatile intermediates in organic
synthesis.[2] Thus, the development of efficient protocols for the
regioselective synthesis of sulfones is an important area of
research in organic synthesis.
SO2R
TsCl
(ref. 11)
CO2H
RO2S
R
R
N
R
TsCN
(ref. 12)
DABCO SO2 + ArN2BF4
This work
(ref. 13)
Classic methods for the synthesis of sulfones include the
reaction of organolithium or Grignard reagents with sulfonyl
chlorides and the oxidation of sulfides.[3] Sulfur dioxide insertion
methods using SO2 gas or its surrogates such as K2S2O5 and
DABCOŸSO2 with nucleophiles, which were pioneered by Willis
and Wu, are also attractive alternatives.[4] However, some of
these methods often suffer from poor functional group
compatibility and generate stoichiometric amounts of
organometallic waste, and the preparation of the starting sulfide
substrate sometimes requires foul-smelling thiols. The Friedel-
Crafts-type sulfonylation of arenes has also been reported,[5] but
these reactions often require harsh conditions. Sulfonylations via
C-H bond functionalization have also been reported, but in most
cases a directing group is required.[6]
Figure 1. Sources of aryl and alkyl sulfonyl radicals.
We considered bench-stable sulfonamides, prepared from
sulfonyl chlorides and α-amino acids in excellent yields, as
alternative reagents for the generation of sulfonyl radicals. Since
silver-catalyzed decarboxylative formations of alkyl radicals are
a well-known transformation,[14] we proposed that if further
fragmentation of the α-amino alkyl radical formed from
sulfonamides occurred via an N-S bond cleavage (Figure 2), the
resultant sulfonyl radical could be used to synthesize sulfones
via the difunctionalization of alkynes and alkenes. We herein
describe the successful development and application of this idea
for the catalytic synthesis of coumarins, which are privileged
molecules in organic chemistry.[15] We also report the results of a
mechanistic study to support the proposed mechanism. The
strategy is also used to synthesize 2-oxindoles[16] and an
isoquinolinedione.
Recently, the reaction of sulfonyl radicals with alkynes and
[a]
[b]
Prof. Dr. K. S. Kanyiva
Global Center for Science and Engineering
School of Advanced Science and Engineering
Waseda University, Shinjuku, Tokyo 169-8555, Japan
E-mail: kanyiva.skm@aoni.waseda.jp
http://www.icsep.sci.waseda.ac.jp/faculty/stephen.html
D. Hamada, S. Makino, H. Takano, Prof. Dr. T. Shibata
Department of Chemistry and Biochemistry
School of Advanced Science and Engineering
Waseda University, Shinjuku, Tokyo 169-8555, Japan
E-mail: tshibata@waseda.jp
R4
CO2H
R4
R3
Ag cat.
fast
SO2R1
R1O2S
R1O2S
R3
N
R2
N
R2
R2
N
CO2
R3
R4
N-sulfonyl
α-amino acid
sulfonyl radical
α-aminoalkyl
radical
http://www.chem.waseda.ac.jp/shibata/
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
Figure 2. Our working hypothesis.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800901
European Journal of Organic Chemistry
COMMUNICATION
We tested our hypothesis by a reaction of phenyl 3-
phenylpropiolate (1a) and N-tosyl proline (2a) in the presence of
AgNO3 (20 mol%) and K2S2O8 (2.0 equiv) in MeCN/H2O (2:1) at
50 ºC for 4 h (Table 1).[17] To our delight, the desired coumarin
3a was obtained in 66% isolated yield. Notably, no by-products
derived from the addition of the α-aminoalkyl radical were
observed under these conditions, which implies that either the α-
aminoalkyl radical is less reactive or the homolytic cleavage of
the N-S bond to form the sulfonyl radical was rapid.
Sulfonamides derived from glycine (2b), alanine (2c), and
phenylalanine (2d) gave lower yields (entries 2-4), while those
derived from valine (2e) and 2-methylalanine (2f) gave
comparatively moderate yields (entries 5-6). N-Tosyl-N-
methylglycine (2g), a tertiary sulfonamide, gave a lower yield
than was achieved with 2a (entry 7). To achieve full conversion
of 1a, we increased the amount of 2a to 1.2 equivalents, which
increased the yield of target coumarin 3a to 73% (entry 8). When
the amount of catalyst was reduced to 5 mol%, the yield
decreased to 57%, and starting material was recovered (entry 9).
Pleasingly, extending the reaction time to 24 h afforded 3a in
79% yield (entry 10). The reaction using tosyl chloride instead of
2 did not proceed at all under present conditions (entry 11).
Furthermore, control experiments revealed that both the silver
catalyst and the oxidant are necessary to achieve the optimum
yield of the coumarin.[17]
3e in 45-70% yields. On the other hand, when m-tolyl-3-
phenylpropiolate was used, regioisomers 3f and 3g were
obtained in a 1:1 ratio. These results clearly indicates that the
reactions proceeded via a 5-exo cyclization and ester migration
as reported by Wu and co-workers.[13a] We also examined
various aryl groups on the alkyne moiety. 4-Chlorophenyl, 4-
biphenyl, and 2-naphthyl groups gave corresponding products
3h, 3i, and 3j in 84%, 59%, and 55% yields, respectively. A
substrate with a methyl group on the alkyne moiety also
participated in the reaction but afforded the desired product 3k
in a lower yield. Finally, when 1,4-diphenylbut-3-yn-2-one (Z =
CH2) was subjected to slightly modified conditions, 2-naphthol 3l
was obtained after enolization.
R2
R2
AgNO3 (5 mol%)
K2S2O8 (2.0 equiv)
Ts
N
Ts
O
+
R1
MeCN/H2O (2:1)
50 ºC, 24 h
(Z = O, CH2)
R1
CO2H
Z
Z
O
2a, 1.2 equiv
1
3
3b: R = Me, 68%
3c: R = t-Bu, 45%
Ph
Ts
O
3d: R = F, 61%
R
O
3e: R = CO2Me, 70%
Ts
O
from p-substituted aryl propiolates
Ph
Ph
O
Me
Ts
O
Ts
O
Table 1. Optimization of the reaction conditions for the sulfonylation of
1a with 2a.[a]
3j, 55%
+
O
O
Me
Ph
Ph
AgNO3 (Y mol%)
K2S2O8 (2.0 equiv)
Me
3f, 32%
3g, 33%
Ts
O
Ts
O
N-Ts α-amino
+
from m-tolyl 3-phenylpropiolate
MeCN/H2O (2:1)
50 ºC, 4 h
acid
O
O
Cl
Ph
O
O
3k, 26%[a]
(Ts = p-CH3C6H4SO2)
2, X equiv
1a
3a
Ph
Ts
O
Ts
O
Ts
OH
Entry
2
X
Y
3a [%][b]
O
O
1
2
3
4
5
2a, N-Ts proline
2b, N-Ts glycine
2c, N-Ts alanine
2d, N-Ts phenylalanine
2e, N-Ts valine
1.0
1.0
1.0
1.0
1.0
20
20
20
20
20
66
19
35
30
59
3l, 30%[b]
3h, 84%
3i, 59%
Scheme 1. Scope of aryl propiolates. Reaction conditions: 1 (0.20 mmol),
2a (0.24 mmol), AgNO3 (0.010 mmol) and K2S2O8 (0.40 mmol) in
CH3CN/H2O (2:1, 3.6 mL) at 50 ºC for 24 h. [a] AgNO3 (10 mol%) was
used. [b] AgNO3 (20 mol%) and K2S2O8 (1.0 equiv) was used.
6
2f, N-Ts 2-methylalanine
1.0
1.0
1.2
1.2
1.2
1.2
20
20
20
5
64
7
2g, N-Ts N-methylglycine
40
Next, the scope of sulfonamides prepared from proline was
examined using 1a as the standard substrate (Table 3). N-
phenylsulfonyl proline reacted with 1a to give the desired
product 3m in 79% yield. As a comparison, a reaction conducted
using sodium benzenesulfinate (PhSO2Na) gave 3m in 42%
yield, indicating the superiority of the sulfonamide.
Arylsulfonamides bearing o-methyl (3n), m-trifluoromethyl (3o),
p-bromo (3p), p-methoxy (3q) and p-phenyl (3r) groups were
also suitable substrates. Compared to arylsulfonyl chlorides
which were required in more amounts and in presence of more
than a stoichiometric amount of base,[11] 1.2 equivalents of the α-
amino acid sulfonamides was enough to afford high yields of
desired products. In contrast to sulfonylation with arylsulfonyl
radicals, the use of alkylsulfonyl radicals is rare. Therefore, we
briefly examined alkylsulfonylations using our catalytic
conditions. Pleasingly, the reactions with n-butyl- and
8
2a
73
9
2a
57
10[c]
11[c]
2a
5
79
TsCl instead of 2
5
N.D.
[a] Conditions: 1a (0.20 mmol), 2 (0.20 or 0.24 mmol), AgNO3 (0.040
or 0.010 mmol) and K2S2O8 (0.40 mmol) in MeCN/H2O (2:1, 3.6 mL) at
50 ºC. [b] Isolated yield. [c] Reaction time of 24 h. N.D.: Not detected.
With the optimized conditions in hand, we subsequently
investigated the scope of aryl propiolates in this radical
cyclization reaction using 2a as the sulfonylation reagent
(Scheme 1). The reactions of 2a with aryl propiolates containing
electron-withdrawing as well as electron-donating groups
proceeded smoothly; p-alkyl, p-fluoro, and p-methoxycarbonyl
groups were tolerated and afforded corresponding products 3b-
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800901
European Journal of Organic Chemistry
COMMUNICATION
standard
conditions
methylsulfonamides proceeded to give 3s and 3t in 47% and
33% yields, respectively. Benzylsulfonamide, however, was
almost fully consumed but gave very low yield of 3u possibly
due to rapid desulfonylation to the stable benzyl radical.
Eq. 1
Eq. 2
3a, traces
1a
2a
+
2a
+
TEMPO or BHT
1.2 equiv
1.2 equiv
standard
conditions
Ph
Ph
Ts
Ph
Ph
Ts
Ph
OH
Ph
4b, 6%
+
+
Ph
AgNO3 (5 mol%)
Ph
SO2R
CO2H
K2S2O8 (2.0 equiv)
N
SO2R
O
1.0 equiv
4a, 18%
+
MeCN/H2O (2:1)
50 ºC, 24 h
O
O
O
CO2Me
N
Ts
2, 1.2 equiv
1a
3
Ph
Ph
O
Ts
O
5,1.2 equiv
MeO2C
Eq. 3
Ph
O
Ph
Ph
O
O
S
O
S
O
S
standard
conditions
CF3
Ph
MeO2C
O
O
O
O
O
Me
1e
3e, not observed
O
O
O
O
3m, 79% (42%)[a]
3n, 45%
3o, 82%
Scheme 3. Experiments to study mechanism.
Br
OMe
Ph
Ph
Ph
O
O
O
Moreover, to probe the relative rates of formation of the
sulfonyl radical from the corresponding α-aminoalkyl radicals as
well as the thermodynamic stability of the α-aminoalkyl radicals
and sulfonyl radical, we performed DFT calculations taking in to
account the MeCN and H2O solvation effects (Table 2).[17] The
overall results indicate that the activation energy to form a
sulfonyl radical from the α-aminoalkyl radical derived from
proline is comparatively lower than that of other α-amino acids.
Notably, the activation energy from the α-aminoalkyl radical
derived from glycine is twice that of proline. In addition, the
thermodynamic stability of the imine derived from proline is also
higher than those of the other amino acids, and the least stable
was that derived from glycine. These DFT calculation results
were in agreement with the isolated yields shown in Table 1. We
think that the α-aminoalkyl radicals are thermodynamically
unstable and undergo rapid N-S bond cleavage to form the
sulfonyl radical and an imine.
S
O
S
O
S
O
O
O
O
O
O
O
3p, 81%
3q, 86%
3r, 65%
Ph
Ph
Ph
O
S
O
S
O
S
Me
Ph
O
O
O
O
O
O
O
O
O
3s, 47%
3t, 33%
3u, <5%
Scheme 2. Scope of sulfonamides. Reaction conditions: 1a (0.20 mmol),
2a (0.24 mmol), AgNO3 (0.010 mmol) and K2S2O8 (0.40 mmol) in
CH3CN/H2O (2:1, 3.6 mL) at 50 ºC for 24 h. [a] PhSO2Na (1.2 equiv) was
used instead of 2.
To probe the mechanism of this sulfonylation reaction,
first, an experiment was carried out in the presence of TEMPO
or BHT as radical scavengers (Scheme 3, Eq. 1). As a result,
the sulfonylation reaction was significantly suppressed. In
addition, the reaction of 2a with 1,1-diphenylethylene under
standard conditions gave tosyl adducts 4a and 4b in 18% and
6% yields, respectively (Eq. 2). These results clearly indicate
that a sulfonyl radical is involved in the reaction mechanism.
Recently, Cheng reported an oxidative generation of arylsulfonyl
radicals from N-sulfonyl-N-aryl propynamides via N-S bond
cleavage under harsh conditions.[18] To confirm whether such
mechanism was probable in our reaction, aryl propiolate 1e was
reacted with methyl N-tosylprolinate (5) under the standard
conditions (Eq. 3). As a result, the corresponding coumarin 3e
was not observed by 1H NMR and most of starting materials
were recovered. This result indicates that our catalytic reaction is
initiated by decarboxylation of the unprotected carboxylic acid.
Table 2. DFT calculations for the formation of sulfonyl radicals from α-
aminoalkyl radicals.
R2
R2
*
R2
R3
SO2Ar
N
R1
SO2Ar
SO2Ar
+
R3
R3
N
R1
N
R1
(Ar = p-CH3C6H4)
ΔG* (kcal/mol)[a]
ΔG (kcal/mol)[b]
α-Amino acid
MeCN
H2O
4.53
MeCN
H2O
Proline
5.15
10.80
8.23
-15.6
-7.6
-17.3
-7.7
Glycine
10.24
7.65
7.40
4.76
9.81
Alanine
-10.6
-10.4
-14.0
-9.2
-10.5
-10.4
-13.6
-10.8
Valine
8.17
2-Methylalanine
N-Methylglycine
5.20
10.40
[a] Activation energy relative to the corresponding α-aminoalkyl radical.
[b] Gibbs free energy relative to the corresponding α-aminoalkyl radical.
On the basis of these mechanistic insights and previous
reports,[13a,14] we considered that the present reaction is initiated
by silver-catalyzed decarboxylative formation of α-aminoalkyl
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800901
European Journal of Organic Chemistry
COMMUNICATION
radical A followed by homolytic N–S bond cleavage to form the
sulfonyl radical and the imine (Scheme 4). The resulting
transient sulfonyl radical regioselectively adds to the alkyne
moiety of 1 to form vinyl radical species B, which is stabilized by
the aryl group (R3). We think that the reason for low yield when
R3 was Me is due to low stability of B. Addition of the vinyl
radical to the aromatic ring at the ipso position gives spirocyclic
intermediate C, which is oxidized to form carbocation D. Ester
migration to thermodynamically favored carbocation E followed
by aromatization then afforded 3.
mechanistic experiments and DFT calculations.
Acknowledgements
We gratefully acknowledge funding support from JSPS via a
Grant-in-Aid for Scientific Research (C) (for K.S.K., No.
18K05114) and a Waseda University grant for Special Research
Projects (for K.S.K., Project No. 2018K-296).
Conflict of interest
–
2–
2–
S2O8
SO4
SO4
+
N
The authors declare no conflict of interests.
R3
O
Ag(II) Ag(I)
SO2R1
CO2H
SO2R1
R2
SO2R1
O
1
N
N
SO2R1
fast
H+, CO2
Keywords: amino acids • coumarins • oxindoles • silver •
A
B
sulfonamides
R3
R2
R2
[O]
R3
O
R3
SO2R1
[1]
For examples, see: a) “Polysulfones”: M. J. El-Hibri, S. A. Weinberg,
Encyclopedia of Polymer Science and Technology, Wiley, New York,
2002; b) P. Ptrasit, Z. Wang, C. Brideau, C. C. Chan, S. Charleson, W.
Cromlish, D. Ethier, J. F. Evans, A. W. Ford-Hutchinson, J. Y. Gauthier
et al., Bioorg. Med. Chem. Lett. 1999, 9, 1773; c) C. F. Sturino, G.
O’Neill, N. Lachance, M. Boyd, C. Berthelette, M. Labelle, L. Li, B. Roy,
J. Scheigetz, N. Tsou et al., J. Med. Chem. 2007, 50, 794; d) D. C.
Meadows, J. Gervay-Hague, Med. Res. Rev. 2006, 26, 793; e) Y.
Tanetani, K. Kaku, K. Kawai, T. Fujioka, T. Shimizu, Pestic. Biochem.
Physiol. 2009, 95, 47; f) A. V. Ivachtchenko, E. S. Golovina, M. G.
Kadieva, O. D. Mitkin, I. M. Okun, Pharm. Chem. J. 2015, 48, 646.
N. S. Simpkins, Sulfones in Organic Synthesis, Pergamon Press,
Oxford, 1993.
3
SO2R1
SO2R1
– H
R2
O
E
O
O
O
D
C
O
Scheme 4. Proposed mechanism for the formation of coumarins and
spirolactone.
The radical cyclization protocol could be extended to the
difunctionalization of electron-deficient alkenes (Scheme 5, Eq.
4, 5). For instance, under the standard conditions, the reactions
of N-aryl acrylamides 1v and 1w with 2a proceeded smoothly
and afforded corresponding 2-oxindoles 3v and 3w in 77% and
70% yields. Finally, catalytic sulfonylation of 1x was also
achieved and provided isoquinolinedione 3x in 50% yield. In
contrast to our recent silver-catalyzed α-aminoalkylation
reaction,[19] no products derived from the addition of α-
aminoalkyl radical to the N-acryl amides were observed.
[2]
[3]
a) S. Oae, Organic Sulfur Chemistry, CRC, Boca Raton, FL, 2017; b) K.
Schank, The Chemistry of Sulfones and Sulfoxides, Wiley, New York,
1988.
[4]
For pioneering reports: a) B. Nyuyen, E. J. Emmett, M. C. Willis, J. Am.
Chem. Soc. 2010, 132, 16372; b) S. Ye, J. Wu, Chem. Commun. 2012,
48, 10037. For reviews: c) E. J. Emmett, M. C. Willis, Asian J. Org.
Chem. 2015, 4, 602; d) G. Liu, C. Fan, J. Wu, Org. Biomol. Chem.,
2015, 13, 1592; e) D. Zheng, J. Wu, Sulfur Dioxide Insertion Reactions
for Organic Synthesis, Nature Springer, Berlin, 2017; f) G. Qiu, K. Zhou,
L. Gao, J. Wu, Org. Chem. Front. 2018, 5, 691.
standard
conditions
R
Ts
R
[5]
a) B. M. Graybill, J. Org. Chem. 1967, 32, 2931; b) M. Ueda, K.
Uchiyama, T. Kano, Synthesis 1984, 323; c) D. U. Singh, P. R. Singh, S.
D. Samant, Tetrahedron Lett. 2004, 45, 9079.
Eq. 4
+
2a
O
N
O
N
Bn
Bn
1v: R = H
1w: R = Cl
1.2 equiv
3v: R = H, 77%
3w: R = Cl, 70%
[6]
[7]
For a review, see: S. Shaaban, S. Liang, N.-W. Liu, G. Manolikakes,
Org. Biomol. Chem. 2017, 15, 1947.
For reviews: a) M. P. Bertrand, C. Ferreri in Radicals in Organic
Synthesis, Vol. 2 (Ed.: P. Renaud, M. Sibi), Wiley-VCH, Weinheim,
2001, pp. 485-504; b) X.-Q. Pan, J.-P Zou, W.-B. Yi, W. Zhang,
Tetrahedron, 2015, 71, 7481; c) Y. Fang, Z. Luo, X. Xu, RSC Adv. 2016,
6, 59661.
Ts
O
standard
conditions
O
Eq. 5
+
2a
NMe
NMe
1.2 equiv
O
1x
O
[8]
a) T. Keshari, R. Kapoorr, L. D. S. Yadav, Eur. J. Org. Chem. 2016,
2695; b) Y.-Y Jiang, S. Liang, C.-C. Zeng, L.-M. Hu, B.-G. Sun, Green
Chem. 2016, 18, 6311; c) L.-J Wang, M. Chen, L. Qi, Z. Xu, W. Li,
Chem. Commun. 2017, 53, 2056; d) Y. Ning, Q. Ji, P. Liao, E. A.
Anderson, X. Bi, Angew. Chem. Int. Ed. 2017, 56, 13805; e) T. C.
Johnson, B. L. Elbert, A. J. M. Farley, T. W. Gorman, C. Genicot, B.
Lallemand, P. Pasau, J. Flasz, J. L. Castro, M. MacCoss, D. J. Dixon, R.
S. Paton, C. J. Schofield, M. D. Smith, M. C. Willis, Chem. Sci. 2018, 9,
629; f) R. J. Griffiths, W. C. Kong, S. A. Richards, G. A. Burley, M. C.
Willis, E. P. A. Talbot, Chem. Sci. 2018, 9, 2295; g) H. Yue, C. Zhu, M.
Rueping, Angew. Chem. Int. Ed. 2018, 57, 1371.
3x, 50%
Scheme 5. Synthesis 2-oxindoles and isoquinolinedione.
In summary, we have described the first catalytic
sulfonylation reaction using sulfonamides prepared from α-amino
acids. The reactions proceeded via decarboxylation and N-S
bond cleavage followed by radical addition/cyclization to form a
C-S bond and C-C bond under moderate conditions. A broad
scope of functional groups was tolerated and gave sulfonylated
[9]
a) X. Li, X. Xu, C. Zhou, Chem. Commun. 2012, 48, 12240; b) W. Wei,
J. Wen, D. Yang, M. Guo, Y. Wang, J. You, H. Wang, Chem. Commun.
2015, 51, 768; c) W. Yu, P. Hu, Y. Fan, C. Yu, X. Yan, X. Li, X. Xu, Org.
Biomol. Chem. 2015, 13, 3308; d) Y.-L. Zhu, B. Jiang, W.-J. Hao, J.-K.
coumarins,
2-oxindoles
and
an
isoquinolinedione
regioselectively. Moreover, the mechanism was supported by
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800901
European Journal of Organic Chemistry
COMMUNICATION
Qiu, J. Sun, D.-C.Wang, P. Wei, A.-F. Wang, G. Li, S.-J. Tu, Org. Lett.
2015, 17, 6078; e) M. Zhang, P. Xie, W. Zhao, B. Niu, W. Wu, Z. Bian,
C. U. Pittman Jr., A. Zhou, J. Org. Chem. 2015, 80, 4176; f) Z.-Z. Chen,
S. Liu, W.-J. Hao, G. Xu, S. Wu, J.-N. Miao, B. Jiang, S.-L. Wang, S.-J.
Tu, G. Li, Chem. Sci. 2015, 6, 6654; g) J. Wen, W. Wei, S. Xue, D.
Yang, Y. Lou, C. Gao, H. Wang, J. Org. Chem. 2015, 80, 4966; h) R.
Fu, W.-J. Hao, Y.-N. Wu, N.-N. Wang, S.-J. Tu, G. Li, B. Jiang, Org.
Chem. Front. 2016, 3, 1452; i) W.-J. Hao, Y. Du, D. Wang, B. Jiang, Q.
Gao, S.-J. Tu, G. Li, Org. Lett. 2016, 18, 1884; j) Y.-L Zhu, B. Jiang,
W.-J. Hao, A.-F. Wang, J.-K. Qiu, P. Wei, D.-C. Wang, G. Li, S.-J. Tu,
Chem. Commun. 2016, 52, 1907.
[10] a) Q. Lu, J. Zhang, G. Zhao, Y. Qi, H. Wang, A. Lei, J. Am. Chem. Soc.
2013, 135, 11481; b) T. Shen, Y. Yuan, S. Song, N. Jiao, Chem.
Commun. 2014, 50, 4115; c) L. Shi, H. Wang, H. Yang, H. Fu, Synlett
2015, 26, 688; d) W. Yang, S. Yang, P. Li, L. Wang, Chem. Commun.
2015, 51, 7520.
[11] a) X. Liu, T. Cong, P. Liu, P. Sun, Org. Biomol. Chem. 2016, 14, 9416;
b) A. Garcia-Dominiguez, S. Muller, C. Nevado, Angew. Chem. Int. Ed.
2017, 56, 9949.
[12] J. Sun, P. Li, L. Guo, F. Yu, Y.-P. He, L. Chu, Chem. Commun. 2018,
54, 3162.
[13] a) D. Zheng, J. Yu, J. Wu, Angew. Chem. Int. Ed. 2016, 55, 11925; b) F.
Liu, J.-Y. Wang, P. Zhou, G. Li, W.-J. Hao, S.-J. Tu, B. Jiang, Angew.
Chem. Int. Ed. 2017, 56, 15570; c) J. Zhang, K. Zhou, J. Wu, Org.
Chem. Front., 2018, 5, 813; d) Z.-J. Shen, Y.-N. Wu, C.-L. He, L. He,
W.-J. Hao, A.-F. Wang, S.-J. Tu, B. Jiang, Chem. Commun. 2018, 54,
445.
[14] For reviews, see: a) M. A. J. Duncton, Med. Chem. Commun. 2011, 2,
1135; b) N. Rodríguez, J. L. Gooßen, Chem. Soc. Rev. 2011, 40, 5030.
[15] For reviews, see: a) R. O. Kennedy, R. D. Thornes, Coumarins: Biology,
Applications and Mode of Action, Wiley, New York, 1997; b) S. K.
Ventata, B. M. Gurupadayya, R. S. Chandan, D. K. Nagesha, B.
Vishiwanathan, Curr. Drug Deliv. 2016, 13, 186.
[16] For a review on synthesis of oxindoles via radical cyclization, see: R.-J.
Song, Y. Lie, Y.-X. Xie, J.-H. Li, Synthesis 2015, 47, 1195.
[17] See the Supporting Information for additional details.
[18] B. Wang, S. Jin, S. Sun, J. Cheng, Org. Chem. Front. 2018, 5, 958.
[19] K. S. Kanyiva, S. Makino. T. Shibata, Chem. Asian J., 2018, 13, 496.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800901
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
K. S. Kanyiva,* D. Hamada, S. Makino,
H. Takano, T. Shibata*
R2
R2
O
S
O
O
R3
Ag cat.
S
R3
N
R1
+
O
Page No. – Page No.
R1
X = O, CH2
R2, R3 = aryl, alkyl
X
O
CO2H
1.2 equiv
α-Amino Acid Sulfonamides as
Versatile Sulfonylation Reagents:
Silver-Catalyzed Synthesis of
Coumarins and Oxindoles by Radical
Cyclization
X
O
up to 86% yield
We describe a silver-catalyzed sulfonylation strategy using sulfonamides derived
from α-amino acids. The reaction proceeded via decarboxylation, N-S bond
cleavage and radical cyclization to provide a variety of coumarins. A wide range of
functional groups was tolerated, and the reaction was suitable for the synthesis of
2-oxindoles and an isoquinolinedione by the capturing of the sulfonyl radical with an
alkene moiety and cyclization. Moreover, the proposed mechanism is supported by
mechanistic experiments and DFT calculations.
This article is protected by copyright. All rights reserved.