Silver(I)-Catalyzed Deprenylation of Allylsulfonamide Derivatives

Article abstract of DOI:10.1055/s-0036-1589066

The silver(I)-catalyzed deprenylation of sulfonamide bearing prenyl functional groups on the nitrogen atom has been developed. In this reaction, the prenyl moiety was selectively eliminated without allyl or benzyl cleavage on the nitrogen atom. In addition, geranyl was also applicable for this elimination reaction. Furthermore, sulfonamide possessing two prenyl groups underwent a double deprenylation to form the corresponding deprenylated sulfonamide. Thus, a novel reactivity between the silver cation and double bond was observed.

Full text of DOI:10.1055/s-0036-1589066

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–D
letter
A
en
F. Inagaki et al.
Letter
Synlett
Silver(I)-Catalyzed Deprenylation of Allylsulfonamide Derivatives
R2
Fuyuhiko Inagaki*
Shisen Hira
0
0
0
0
0-
0
0
3
2-
9
9
9
0-
8
3
X
AgSbF6
(5 mol%)
O
S
H
O
S
R1
N
R1
N
R3
Chisato Mukai
DCE
MW (140 °C)
2 min
R3
O
O
R1 = Ph, p-tolyl, Me
2 = Me,
R3 = H, allyl, Bn
up to >99% yield
Division of Pharmaceutical Sciences, Graduate
School of Medical Sciences, Kanazawa University,
Kakuma-machi, Kanazawa 920-1192, Japan
finagaki@p.kanazawa-u.ac.jp
R
R2
AgSbF6
(5 mol%)
O
S
H
H
O
R1
N
R1
S
N
DCE
MW (140 °C)
2 min
O
O
R2
up to 98% yield
Received: 13.05.2017
Accepted after revision: 30.05.2017
Published online: 11.07.2017
the double bond has the potential for causing additional re-
action modes. We now report the selective deprenylation of
allylsulfonamide 3 using a catalytic amount of AgSbF6.
DOI: 10.1055/s-0036-1589066; Art ID: st-2017-u0355-l
Previous study
Abstract The silver(I)-catalyzed deprenylation of sulfonamide bearing
prenyl functional groups on the nitrogen atom has been developed. In
this reaction, the prenyl moiety was selectively eliminated without allyl
or benzyl cleavage on the nitrogen atom. In addition, geranyl was also
applicable for this elimination reaction. Furthermore, sulfonamide pos-
sessing two prenyl groups underwent a double deprenylation to form
the corresponding deprenylated sulfonamide. Thus, a novel reactivity
between the silver cation and double bond was observed.
AgSbF6
MeO2C
MeO2C
MeO2C
(5 mol%)
MeO2C
DCE
Δ (MW)
2
1
This study
AgSbF6
(5 mol%)
O
H
R
O
Key words C–N bond cleavage, silver, catalytic reaction, deprenyla-
tion, alkene
R'
S
N
R'
S
N
DCE
Δ (MW)
O
R
O
3
4
Since the discovery of the antibacterial drug, prontosil,1
the sulfonamide moiety is widely accepted as one of the
most important bioisosteres2 of the carboxylic acid in me-
dicinal chemistry. For further investigation regarding bioac-
tive materials bearing the sulfonamide, a higher level of
synthetic methods is required. Although several types of
protecting groups for sulfonamide, such as tert-butyl,3–5
functionalized benzyl,6–11 and allyl12–14 are already known,
the selective deprotection processes (C–N bond cleavage)
are still limited. On the other hand, silver salts are used for
the catalytic reactions with alkynes due to the alkyno-
philicities.15–18 Silver-ion chromatography is also well-
known for separating lipids containing double bonds.19–22
With regard to the principle of this separation, the silver-
ion complexes with the double bonds.23,24 However, inter-
estingly, silver-catalyzed reactions with alkenes are limit-
ed.25,26 Based on this information, we recently developed27
the silver(I)-catalyzed cycloisomerization of a diene 1 in-
volving alkyl rearrangements to form a cyclic product 2
(Scheme 1). Thus, it seemed that silver coordination with
Scheme 1 Silver(I)-catalyzed reaction of olefins
After several examinations, we found that the selective
deprenylation reaction of N-allyl-N-prenyl-p-toluenesul-
fonamide (5a) with 5 mol% of AgSbF6 in DCE at 140 °C (mi-
crowave irradiation) for two minutes gave N-allyl-p-tolue-
nesulfonamide (6a) in 84% yield (Scheme 2). More recently,
Jirgensons14 reported the same reaction using 6.5 equiva-
lents of TFA and 6 equivalents of Et3SiH in CH2Cl2 at room
temperature for 60 minutes to afford 6a in 68% yield.28 Al-
though our reaction conditions required a higher tempera-
ture, the chemical yields and reaction time were better. Al-
so, an excess amount of a cation scavenger, such as Et3SiH,
was not required for our reaction, which must be another
benefit. In addition, they reported that the deprenylation
reaction of N-prenyl-p-toluenesulfonamide (7a) led to a
complex mixture, whereas our reaction gave the tosylamide
8a in 89% yield.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

B
F. Inagaki et al.
Letter
Synlett
Table 1 Silver(I)-Catalyzed Monodeallylation of Allylsulfonamide
AgSbF6
(5 mol%)
Yield (%)a
TsHN
Entry
Substrate
Product
TsN
DCE
140 °C (MW)
2 min
5a
7a
6a
84% yield
PhO2SHN
1
PhO2SN
88
AgSbF6
(5 mol%)
6b
TsNH2
5b
DCE
140 °C (MW)
1 min
TsHN
8a
89% yield
MsHN
Scheme 2 Silver(I)-catalyzed deprenylation
2
82b
MsN
6c
5c
Our next effort focused on the exploration of the scope
and limitations. These results are summarized in Table 1.
Selective deprenylation between the prenyl and allyl moi-
eties smoothly occurred in not only the tosylamide 5a but
also for the benzenesulfonamide 5b and mesylamide 5c af-
fording 6b (88%) and 6c (82%) in high yields (Table 1, entries
1 and 2). Substrate 5d bearing prenyl and benzyl groups
provided the deprenylation product 6d in 69% yield without
debenzylation (Table 1, entry 3). Jirgensons and co-work-
ers14 reported that the reaction of 5d using TFA and Et3SiH
did not afford 6d, thus the difference in the reactivities be-
tween both conditions must be clarified. Although elimina-
tion of the 2-butenyl group from substrate 5e required a
higher temperature (180 °C), the allylsulfonamide 6b was
observed in a modest yield (Table 1, entry 4). For the depre-
nylation using monoprenyl substrates 7b,c, the correspond-
ing benzenesulfonamide (8b) and mesylamide (8c) were
obtained in good yields (Table 1, entries 5 and 6). A similar
type of deallylation also occurred using the geranyl group
instead of the prenyl group. Actually, the tosylamide 8a
(82%) was observed from the N-geranyl substrate 7d (Table
1, entry 7). Although other silver salts (AgBF4, AgOAc, etc.)
were examined in several substrates, satisfied results were
not observed (0–31% yield). In addition, heating conditions
without silver salt did not afford the desired product.
To elucidate the mechanism in detail, an efficient radical
inhibitor, butylated hydroxytoluene (BHT), was applied to
the deprenylation reaction (Scheme 3). When the diene 5a
was treated with one equivalent BHT and 5 mol% AgSbF6,
the deprenylated product 6a was observed in 73% yield
(84% without BHT), which encouraged us to consider that
the main reaction proceeded without a free-radical mecha-
nism.
TsHN
3
4
69
Ph
TsN
6d
Ph
5d
PhO2SHN
PhO2SN
46c
6b
5e (mixture of E/Z = 3:1)
PhO2SNH2
8b
5
6
78
PhO2SHN
7b
MsNH2
8c
quant.
MsHN
7c
TsNH2
8a
7
82
TsHN
7d
aSubstrate was reacted with 5 mol% AgSbF6 in DCE at 140 °C (MW) for 2
min.
bReacted for 80 s.
cReacted at 180 °C using oil bath for 30 min.
BHT
(1 equiv)
AgSbF6
(5 mol%)
TsHN
Based on these results, the plausible mechanisms of de-
prenylation are shown in Scheme 4. Coordination with both
the prenyl double bond and sulfonyl moiety of substrate 3
would form complex A. When the addition of the sulfon-
amide to the cationic silver produces intermediate B, depro-
tonative elimination at the prenyl group should provide the
deprenylated intermediate C. In parallel, the double bond of
TsN
DCE
140 °C (MW)
2 min
5a
6a
73% yield
Scheme 3 Addition of radical scavenger
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

C
F. Inagaki et al.
Letter
Synlett
the prenyl part is also a candidate for the addition to the sil-
ver cation, which would form complex B′. Intermediates B
and B′ might be present in equilibrium. The common de-
prenylated complex C would then be constructed by the
deprotonation and [3,3]-sigmatropic rearrangement of B′.
Finally, the protodeargentation from C could form the cor-
responding products 4.
into the corresponding sulfonamides 8a–c successfully pro-
ceeded in good yields. In addition, the bisgeranyl function-
alities on the nitrogen of the sulfonamides 10a–c were also
possible to be eliminated. The resulting sulfonamides 8a–c
were observed in 54, 68, and 81% yield, respectively.
In summary, we developed the silver(I)-catalyzed selec-
tive deprenylation of the sulfonamide possessing allyl func-
tional groups on the nitrogen atom.28,29 This C–N bond
cleavage simply proceeded by adding only a catalytic
amount of AgSbF6 at high temperature, and other reagents,
such as an excess amount of a cation scavenger, were not
required. In addition, the prenyl elimination selectively oc-
curred without allyl or benzyl cleavage on the nitrogen at-
om. The geranyl group was also an active functionality for
this elimination reaction. Furthermore, the double depre-
nylation of bisprenyl sulfonamide was also possible. Thus,
we determined the novel reactivity between the silver cat-
ion and double bond. Further examinations using the silver
catalyst and alkenes are currently under way.
O
S
O
S
R'
NR
R'
NHR
3
Ag
O
4
O
coordination
protodeargentation
R
N
Ag
O
O
R'
S
Ag
R'
S
NR
C
A
O
O
deprotonative
elimination
addition
H
H
R
R
N
N
O
R'
O
R'
Acknowledgment
S
Ag
S
Ag
O
B
B'
O
We are grateful for the support of a Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science, and
Technology (Japan).
Scheme 4 Plausible mechanisms
Based on the speculated mechanisms requiring the pre-
nyl moiety and sulfonamide, another substitution group R
on the nitrogen atom must not be directly involved in the
deprenylation reaction. In other words, if the R group has a
prenyl functionality, R would also be eliminated. Thus, the
double deprenylation reaction was finally examined. As
shown in Scheme 5, conversions of the bisprenyl sulfon-
amides 9a–c bearing p-tolyl, phenyl, and methyl groups
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1589066.
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References and Notes
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O
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R
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O
O
10a (R = p-tolyl)
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Scheme 5 Silver(I)-catalyzed double deprenylation
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D

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Letter
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814, 666, 550 cm–1. 1H NMR (600 MHz, CDCl3): δ = 7.76 (d, 2 H,
J = 8.1 Hz), 7.31 (d, 2 H, J = 8.1 Hz), 5.76–5.69 (m, 1 H), 5.19–5.15
(m, 1 H), 5.11–5.09 (m, 1 H), 4.53 (br t, 1 H, J = 5.8 Hz), 3.60–
3.58 (m, 2 H), 2.43 (s, 3 H). 13C NMR (151 MHz, CDCl3): δ =
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–D