Thioesterification and Selenoesterification of Amides via Selective N-C Cleavage at Room Temperature: N-C(O) to S/Se-C(O) Interconversion

Article abstract of DOI:10.1055/s-0039-1690055

The direct nucleophilic addition to amides represents an attractive methodology in organic synthesis that tackles amidic resonance by ground-state destabilization. This approach has been recently accomplished with carbon, nitrogen and oxygen nucleophiles.

Full text of DOI:10.1055/s-0039-1690055

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–G
paper
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en
Md. M. Rahman et al.
Paper
Synthesis
Thioesterification and Selenoesterification of Amides via Selective
N–C Cleavage at Room Temperature: N–C(O) to S/Se–C(O) Inter-
conversion
Md. Mahbubur Rahman
O
Guangchen Li
R
R
O
R
R
SH
SeH
O
S
R
S
– NR'R''
Michal Szostak*
0
0
0
0-
0
0
0
2-9
6
5
0-9
6
9
0
R'
O
R1
N
R
N
R'
K3PO4
R
R''
R''
R
Se
RT
Department of Chemistry, Rutgers University,
73 Warren Street, Newark, NJ 07102, USA
michal.szostak@rutgers.edu
amides
tetrahedral intermediate
84–96% yield
thioesters
selenoesters
16 examples
Received: 31.12.2019
Accepted after revision: 26.01.2020
Published online: 25.02.2020
A: Amide bond cross-coupling: new platform for synthesis
-reviews: ref. 4
O
R
R
R'
DOI: 10.1055/s-0039-1690055; Art ID: ss-2019-c0716-op
R
O
[M]n
acyl coupling
n+2
N
R'
O
R
N
R''
[M]
Abstract The direct nucleophilic addition to amides represents an at-
tractive methodology in organic synthesis that tackles amidic reso-
nance by ground-state destabilization. This approach has been recently
accomplished with carbon, nitrogen and oxygen nucleophiles. Herein,
we report an exceedingly mild method for the direct thioesterification
and selenoesterification of amides by selective N–C(O) bond cleavage in
the absence of transition metals. Acyclic amides undergo N–C(O) to
S/Se–C(O) interconversion to give the corresponding thioesters and
selenoesters in excellent yields at room temperature via a tetrahedral
intermediate pathway (cf. an acyl metal).
ground-state
-destabilization
R''
Lm
R
R
amides
Amides = key synthetic building blocks
decarbonylative
coupling
selective N−C activation
B: Transition-metal-free activation of amides via tetrahedral intermediates
-review: ref. 9
O
R
O
O
R
X
– NR'R''
R'
R1
N
R
N
R'
R
R
ground-state
-destabilization
R''
R''
amides
acyl coupling
tetrahedral intermediate
Key words amides, N–C activation, metal-free, thioesters, seleno-
esters, thioesterification, selenoesterification, tetrahedral intermediates
C: This work: Thioesterification and selenoesterification of amides at RT
O
R
R
R
O
R
R
SH
SeH
O
S
R
R
S
– NR'R''
R'
O
Amides represent an extremely important class of func-
tional groups in chemistry.1 As a result, the development of
new methods for the direct interconversion of amides has
been a field of intense study since the early days of organic
synthesis.2,3 The last five years have witnessed the estab-
lishment of powerful amide bond cross-coupling reactions
by selective N–C(O) cleavage enabled by the amide bond
twist and ground-state destabilization concept introduced
by our group in 2015 (Figure 1A).4–7 These reactions enable
the use of amides in generic cross-coupling reactions of
high synthetic value via acyl and aryl intermediates (after
CO loss)4b using Pd, Ni, Rh, Co and Cr catalysis.8 Of particular
interest is the fact that acyl-type reactivity of amides is fea-
sible in the absence of transition metals via a direct nucleo-
philic addition pathway involving tetrahedral intermediates
(Figure 1B).9 This mode of reactivity has been accomplished
with carbon, nitrogen and oxygen nucleophiles,10 and relies
on the capacity of the amide bond to undergo ground-state
destabilization to overcome amidic resonance (15–20
kcal/mol, nN → *CO conjugation).
R1
N
R
N
R'
K3PO4
R''
R''
Se
RT
amides
tetrahedral intermediate
84–96% yield
thioesters
selenoesters
16 examples
benign sustainable
orthogonal selectivity
mild [N−C(O) to S/Se−C(O)] interconversion
user-friendly valuable S and Se products
Figure 1 (A) Cross-coupling of amides. (B) Transition-metal-free acti-
vation of amides. (C) Thioesterification and selenoesterification of am-
ides, N–C(O) to S/Se–C(O) interconversion at room temperature (this
work).
In this article, we report an exceedingly mild method for
direct thioesterification11 and selenoesterification12 of am-
ides by selective N–C(O) bond cleavage in the absence of
transition metals (Figure 1C). Acyclic amides undergo N–
C(O) to S/Se–C(O) interconversion to give the corresponding
thioesters and selenoesters in excellent yields at room tem-
perature via a tetrahedral intermediate pathway (cf. an acyl
metal). More broadly, this methodology enables rapid ac-
cess to thioester and selenoester architectures from am-
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Md. M. Rahman et al.
Paper
Synthesis
ides13,14 and further highlights the advantages of this mild
transition-metal-free tactic of amide bond functional group
interconversion.
Table 1 Optimization of the Thioesterification of Amides by Selective
N–C(O) Bond Cleavage at Room Temperaturea
O
SH
O
Transition-metal-free reactions of amides create new
opportunities for organic synthesis by exploiting the tetra-
hedral intermediate avenue of ground-state destabilized
amides. In this context, N-acyl-tosylamides [Ar = Ph, R = Ph,
RE (resonance energy) = 9.7 kcal/mol; Winkler–Dunitz
parameters, τ = 18.8°; χN = 18.9°]5a have been established as
broadly useful amides to achieve both (1) amide bond
interconversion via direct metal insertion into the N–C(O)
bond, and (2) amide bond interconversion via tetrahedral
intermediates in the absence of transition metals.4–9
Encouraged by our results on transition-metal-free es-
terification and transamidation reactions of N-acyl-tosyl-
amides,9,10 we focused our efforts on identifying optimum
conditions for mild, transition-metal-free thioesterification
(Table 1). We were delighted to find that the reaction pro-
ceeded in excellent yield at room temperature using excess
of K3PO4 as a base and close to a stoichiometric amount of
thiophenol (Table 1, entry 1). Under these conditions, cleav-
age of the alternative amide bond was not observed, consis-
tent with the high capacity of N-tosylamide to activate the
acyclic amide bond. Furthermore, the amount of base could
be decreased to 2.0 equivalents without deleterious effect
(Table 1, entry 2); however, further decrease resulted in
lower reaction efficiency (Table 1, entry 3). A brief solvent
screen indicated THF to be the optimal solvent; however,
reasonable efficiency was also observed in dioxane, CH2Cl2,
toluene and MeCN (Table 1, entries 4–7). Finally, solvent
concentration is an important parameter (Table 1, entries 8
and 9), and as expected in transition-metal-free intercon-
version of amides favors the acyl addition over the amide
N-deprotection pathway.
With optimized conditions in hand, we next evaluated
the scope of amides and thiols that participate in this mild
N–C(O) to S–C(O) interconversion (Table 2). We were de-
lighted to find that a broad range of amides was compatible
with these mild conditions, including neutral (3a,b), elec-
tron-rich (3c), electron-deficient (3d), and sterically hin-
dered (3e) amides. Pleasingly, the reaction was compatible
with sensitive halide substituents such as bromo (3f),
which would be problematic in transition-metal-catalyzed
protocols. Furthermore, full chemoselectivity in the nucleo-
philic addition to the amide bond occurred in the presence
of an alkyl ester (3g), indicating that N–Ts amides (RE = 9.7
kcal/mol) are the preferred addition site over methyl esters
(C–O isomerization barrier, 12.8 kcal/mol). The reaction
was also compatible with heterocycles (3h) and aliphatic
amides (3i). Furthermore, we were pleased to find that elec-
tron-rich (3j) as well as more challenging electron-poor
Ph
K3PO4
N
S
+
Ts
solvent, RT
1a
2a
3a
Entry
K3PO4 (equiv)
Solvent
Yield (%)b
1
3.0
2.0
1.5
2.0
2.0
2.0
2.0
2.0
2.0
THF
>98
>98
81
2
THF
3
THF
4
dioxane
CH2Cl2
toluene
MeCN
THF
86
5
91
6
95
7
87
8c
9d
93
THF
91
a Reaction conditions: amide (1.0 equiv), thiol (1.2 equiv), K3PO4 (1.5–3.0
equiv), solvent (0.25 M), 25 °C, 15 h.
b GC/1H NMR yields.
c Concentration: 0.50 M.
d Concentration: 1.0 M.
benzenethiols (3k,l) underwent the desired addition in ex-
cellent yields. Moreover, this protocol could be applied to
sterically hindered benzenethiols (3m), while less challeng-
ing aliphatic thiols (3n, vide infra) were also well tolerated.
Finally, we were pleased to find that this protocol could be
extended to N–Ms amides bearing an atom-economic N-
mesyl activating group, without any decrease in the reac-
tion efficiency (Table 2, entry 15). Note that N-alkyl amides,
such as N–Me, are also amenable substrates. 2-Pyridylthiols
have not been tested at this stage of reaction development.
Future studies will address the use of disulfides under re-
ductive conditions. Overall, this mild N–C(O) to S–C(O) in-
terconversion method enables the preparation of a variety
of valuable thioesters from amides. Given the plethora of
metal-catalyzed and metal-free reactions of thioesters as
well as the importance of thioesters in biochemical tagging,
this mild process provides a useful alternative inter-
connecting amides with thioesters.11,15
To further demonstrate the synthetic potential of this
approach, we applied this method to the synthesis of a
selenoester using PhSeH via N–C(O) to Se–C(O) interconver-
sion (Scheme 1). Since selenoesters represent an important
class of acyl transfer reagents and radical precursors in or-
ganic synthesis, while recent studies have shown their util-
ity in chemical ligation, our mild method permits the use of
amides as selenoester precursors.12,15
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

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Md. M. Rahman et al.
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Synthesis
Table 2 Substrate Scope of the Thioesterification of Amides by N–C Cleavage at Room Temperaturea
O
SH
Ar2
O
Ar2
Ph
K3PO4 (2.0 equiv)
N
S
+
Ar1
Ar1
R
THF, RT
1, R = Ts, Ms
Thiol (2)
2 (1.2 equiv)
3
Entry
1
Amide (1)
Product (3)
Yield (%)b
O
O
SH
Ph
3a
3b
92
93
N
S
Ts
O
O
SH
SH
Ph
2
3
N
S
Ts
Me
Me
O
O
Ph
3c
91
N
S
Ts
MeO
F3C
MeO
O
O
SH
SH
SH
Ph
N
4
5
6
3d
3e
3f
94
86
90
S
Ts
F3C
Me
Me
O
O
Ph
N
S
Ts
O
O
Ph
N
S
Ts
Br
Br
O
O
SH
Ph
7
N
3g
89
S
Ts
MeO2C
MeO2C
O
O
SH
SH
Ph
8
9
3h
3i
88
85
N
S
O
Ts
O
O
O
Me
Ph
Me
N
6
S
6
Ts
OMe
CF3
F
O
O
O
O
SH
SH
Ph
10
3j
94
N
S
MeO
F3C
Ts
Ph
11
12
13
3k
3l
84
86
92
N
S
Ts
O
O
O
O
SH
Ph
Ph
N
S
S
F
Ts
Me
SH
3m
N
Ts
Me
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

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Md. M. Rahman et al.
Paper
Synthesis
Table 2 (continued)
Entry
Amide (1)
Thiol (2)
Product (3)
Yield (%)b
O
O
Ph
Ph
Me
SH
14
3n
3a
96
92
N
S
Me
7
7
Ts
O
O
SH
15
N
S
Ms
a Reaction conditions: amide (1.0 equiv), thiol (1.2 equiv), K3PO4 (2.0 equiv), THF (0.25 M), 25 °C, 15 h.
b Yield of isolated product.
O
O
To gain preliminary insight on the reaction mechanism,
Ph
N
Ts
S
2a (1 equiv)
K3PO4, THF
we performed intermolecular competition experiments
(Schemes 2–5). Most interestingly, intermolecular competi-
tion between thiophenol and phenol indicated similar reac-
tivity (3a/3p = 45:55) (Scheme 2), which bodes well for fu-
ture application of this [N–C(O) → S–C(O)] protocol in or-
ganic synthesis. Note that the ester is unreactive under the
reaction conditions. Excess of reagents were used to stop
the reaction at <30% conversion. Furthermore, electron-
MeO
F3C
MeO
F3C
1c (3 equiv)
3c
+
+
RT, 15 h
O
O
Ph
3d/3c = 70:30
N
Ts
S
1d (3 equiv)
3d
Scheme 3 Selectivity study on the thioesterification of amides at room
temperature: electron-rich vs electron-deficient amides
deficient
amides
are
inherently
more
reactive
(3d/3c = 70:30) (Scheme 3), which is consistent with the
electrophilicity of the amide bond.
OMe
O
SH
S
1a (1 equiv)
K3PO4, THF
O
SeH
O
MeO
2b (3 equiv)
Ph
K3PO4 (2.0 equiv)
3j
N
Se
+
+
+
CF3
RT, 15 h
Ts
THF, RT
O
SH
1a
2g (1.2 equiv)
3o: 92% yield
3j/3k = 95:5
S
Scheme 1 Selenoesterification of an amide by N–C cleavage at room
temperature
F3C
2c (3 equiv)
3k
Scheme 4 Selectivity study on the thioesterification of amides at room
temperature: electron-rich vs electron-deficient thiols
O
SH
S
O
K3PO4, THF
RT, 15 h
2a (3 equiv)
OH
3a
Ph
O
N
+
+
SH
Ts
S
O
1a (1 equiv)
K3PO4, THF
1a
3a/3p = 45:55
O
2a (3 equiv)
3a
+
+
2h (3 equiv)
3p
RT, 15 h
O
Scheme 2 Selectivity study on the thioesterification of amides at room
temperature: thiophenol vs phenol
Me
SH
3n/3a >95:5
S
Me
7
7
2f (3 equiv)
3n
Scheme 5 Selectivity study on the thioesterification of amides at room
temperature: aromatic vs aliphatic thiol nucleophiles
Moreover, electron-rich thiophenols react preferentially
(3j/3k = 95:5) (Scheme 4), while aliphatic thiols are signifi-
cantly more reactive than aromatic thiols (3n/3a >95:5)
(Scheme 5). Overall, these experiments are consistent with
thiol nucleophilicity via a tetrahedral addition pathway.
In conclusion, we have reported a mild method for the
direct thioesterification and selenoesterification of amides
by selective N–C(O) bond cleavage. This protocol is high-
lighted by the absence of transition metals, operational
simplicity and excellent reaction efficiency. It is worthwhile
to point out that all amides used could be conveniently pre-
pared from common secondary or primary amides.4a–g Our
future studies will implement this transition-metal-free
manifold in medicinal chemistry targets. More generally,
this tactic accomplishes [N–C(O) → S/Se–C(O)] interconver-
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Md. M. Rahman et al.
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Synthesis
sion to connect amides with thioesters and selenoesters.
The tetrahedral intermediate pathway of ground-state de-
stabilized amides is a serious alternative to acyl metals that
should be considered as an alternative approach in all occa-
sions when available.4–9
nal standard, and by comparison with authentic samples. Purification
by chromatography on silica gel (EtOAc/hexanes) afforded the analyt-
ically pure product.
S-Phenyl Benzothioate (3a)
White solid; yield: 19.7 mg (92%).
1H NMR (500 MHz, CDCl3):  = 8.04 (d, J = 8.1 Hz, 2 H), 7.62 (t, J = 7.4
Hz, 1 H), 7.55–7.45 (m, 7 H).
13C NMR (126 MHz, CDCl3):  = 190.45, 137.00, 135.43, 133.98,
129.85, 129.59, 129.09, 127.82, 127.71.
The starting materials reported in the manuscript have been previ-
ously described in the literature or are prepared by a previously re-
ported method. All products have been previously reported, see the
Supporting Information for details. All solvents were purchased at the
highest commercial grade and used as received or after purification
by passing through activated alumina columns or by distillation from
Na/benzophenone. All solvents were deoxygenated prior to use. All
other chemicals were purchased at the highest commercial grade and
used as received. Reaction glassware was oven-dried at 140 °C for at
least 24 h or flame-dried prior to use, allowed to cool under vacuum
and purged with argon (three cycles). Flash chromatography was per-
formed using SiliCycle silica gel (60 Å, 300 mesh). TLC analysis was
carried out on Analtech glass plates coated with silica gel 60 F254 (0.2
mm thickness). The plates were visualized using a 254 nm ultraviolet
lamp or aqueous potassium permanganate solution. 1H NMR, 13C NMR
and 19F NMR spectra were recorded in CDCl3 on Bruker and Varian
spectrometers at 500 MHz (1H NMR), 125 MHz (13C NMR) and 471
MHz (19F NMR). All shifts are reported in parts per million (ppm) rela-
tive to the residual CHCl3 resonances (7.27 and 77.2 ppm, 1H NMR and
13C NMR, respectively). All coupling constants (J) are reported in hertz
(Hz); standard abbreviations are used for multiplicities. GC-MS chro-
matography was performed using an Agilent HP6890 GC System and
an Agilent 5973A inert XL EI/CI MSD using helium as the carrier gas at
a flow rate of 1 mL/min and an initial oven temperature of 50 °C.
1H NMR, 13C NMR and 19F NMR spectra are given for all compounds in
the Supporting Information for characterization purposes.
S-Phenyl 4-Methylbenzothioate (3b)
White solid; yield: 21.2 mg (93%).
1H NMR (500 MHz, CDCl3):  = 7.94 (d, J = 8.2 Hz, 2 H), 7.56–7.50 (m, 2
H), 7.48–7.43 (m, 3 H), 7.29 (d, J = 8.1 Hz, 2 H), 2.44 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 190.02, 144.91, 135.46, 134.45,
129.75, 129.53, 127.91, 22.06.
S-Phenyl 4-Methoxybenzothioate (3c)
White solid; yield: 22.3 mg (91%).
1H NMR (500 MHz, CDCl3):  = 8.04–7.99 (m, 2 H), 7.54–7.49 (m, 2 H),
7.48–7.43 (m, 3 H), 6.98–6.94 (m, 2 H), 3.89 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 188.91, 164.34, 135.53, 130.05,
129.77, 129.70, 129.50, 128.01, 114.26, 55.89.
S-Phenyl 4-(Trifluoromethyl)benzothioate (3d)
White solid; yield: 26.6 mg (94%).
1H NMR (500 MHz, CDCl3):  = 8.14 (d, J = 8.2 Hz, 2 H), 7.76 (d, J = 8.2
Hz, 2 H), 7.54–7.51 (m, 2 H), 7.50–7.47 (m, 3 H).
13C NMR (126 MHz, CDCl3):  = 189.72, 139.79, 135.33, 135.27 (q,
JC–F = 32.9 Hz), 130.22, 129.76, 128.17, 126.91, 126.19 (q, JC–F = 3.7 Hz),
123.84 (q, JC–F = 273.3 Hz).
Thioesterification of Amides; General Procedure
19F NMR (471 MHz, CDCl3):  = –63.13.
An oven-dried reaction flask equipped with a stir bar was charged
with an amide substrate (0.10 mmol, 1.0 equiv), thiol (0.12 mmol, 1.2
equiv) and K3PO4 (0.20 mmol, 2.0 equiv). THF (0.40 mL, 0.25 M) was
added with vigorous stirring at room temperature, and the reaction
mixture was stirred at room temperature for 15 h. The reaction mix-
ture was then diluted with CH2Cl2 (3 mL), filtered and washed with
water (3 mL). The aqueous layer was extracted with CH2Cl2 (2 × 3 mL)
and the combined organic layers were dried, filtered, and concentrat-
ed. The sample was analyzed by 1H NMR (500 MHz, CDCl3) and GC-
MS to obtain the conversion, yield and selectivity using an internal
standard, and by comparison with authentic samples. Purification by
chromatography on silica gel (EtOAc/hexanes) afforded the analytical-
ly pure product.
S-Phenyl 2-Methylbenzothioate (3e)
Colorless oil; yield: 19.6 mg (86%).
1H NMR (500 MHz, CDCl3):  = 7.95 (d, J = 7.7 Hz, 1 H), 7.54–7.51 (m, 2
H), 7.50–7.40 (m, 4 H), 7.34–7.26 (m, 2 H), 2.50 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 192.50, 137.77, 137.13, 135.25,
132.34, 132.09, 129.80, 129.60, 128.97, 128.59, 126.20, 21.10.
S-Phenyl 4-Bromobenzothioate (3f)
White solid; yield: 26.4 mg (90%).
1H NMR (500 MHz, CDCl3):  = 7.92–7.87 (m, 2 H), 7.66–7.62 (m, 2 H),
7.53–7.49 (m, 2 H), 7.48–7.46 (m, 3 H).
13C NMR (126 MHz, CDCl3):  = 189.59, 135.77, 135.39, 132.41,
Selenoesterification of Amides; General Procedure
An oven-dried reaction flask equipped with a stir bar was charged
with an amide substrate (0.10 mmol, 1.0 equiv), selenol (0.12 mmol,
1.2 equiv) and K3PO4 (0.20 mmol, 2.0 equiv). THF (0.40 mL, 0.25 M)
was added with vigorous stirring at room temperature, and the reac-
tion mixture was stirred at room temperature for 15 h. The reaction
mixture was then diluted with CH2Cl2 (3 mL), filtered and washed
with water (3 mL). The aqueous layer was extracted with CH2Cl2 (2 × 3
mL) and the combined organic layers were dried, filtered, and concen-
trated. The sample was analyzed by 1H NMR (500 MHz, CDCl3) and
GC-MS to obtain the conversion, yield and selectivity using an inter-
130.05, 129.68, 129.27, 129.09, 127.23.
Methyl 4-[(Phenylthio)carbonyl]benzoate (3g)
White solid; yield: 24.3 mg (89%).
1H NMR (500 MHz, CDCl3):  = 8.15 (d, J = 8.5 Hz, 2 H), 8.08 (d, J = 8.5
Hz, 2 H), 7.54–7.50 (m, 2 H), 7.50–7.45 (m, 3 H), 3.97 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 190.07, 166.42, 140.33, 135.35,
134.79, 130.33, 130.12, 129.73, 127.76, 127.19, 52.88.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

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Md. M. Rahman et al.
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Synthesis
S-Phenyl Furan-2-carbothioate (3h)
13C NMR (126 MHz, CDCl3):  = 192.41, 137.63, 133.48, 128.85,
127.50, 32.22, 29.90, 29.88, 29.84, 29.63, 29.50, 29.39, 29.28, 23.01,
14.43.
Colorless oil; yield: 17.9 mg (88%).
1H NMR (500 MHz, CDCl3):  = 7.63 (d, J = 0.9 Hz, 1 H), 7.52–7.49 (m, 2
H), 7.47–7.43 (m, 3 H), 7.26 (dd, J = 3.6, 0.5 Hz, 1 H), 6.58 (dd, J = 3.5,
1.7 Hz, 1 H).
Se-Phenyl Benzoselenoate (3o)
Yellow oil; yield: 24.0 mg (92%).
1H NMR (500 MHz, CDCl3):  = 7.98–7.91 (m, 2 H), 7.65–7.58 (m, 3 H),
7.50 (t, J = 7.8 Hz, 2 H), 7.46–7.41 (m, 3 H).
13C NMR (126 MHz, CDCl3):  = 178.95, 150.70, 146.79, 135.47,
129.98, 129.58, 126.53, 116.56, 112.75.
S-Phenyl Decanethioate (3i)
13C NMR (126 MHz, CDCl3):  = 193.72, 138.89, 136.68, 134.23,
129.72, 129.41, 129.29, 127.69, 126.14.
Colorless oil; yield: 22.5 mg (85%).
1H NMR (500 MHz, CDCl3):  = 7.44–7.37 (m, 5 H), 2.65 (t, J = 7.5 Hz, 2
H), 1.74–1.68 (m, 2 H), 1.35–1.25 (m, 12 H), 0.89 (t, J = 6.9 Hz, 3 H).
13C NMR (126 MHz, CDCl3):  = 197.91, 134.82, 129.61, 129.48,
Funding Information
128.35, 44.09, 32.19, 29.72, 29.60, 29.59, 29.31, 25.95, 23.01, 14.45.
Rutgers University and the National Science Foundation (NSF, CAREER
CHE-1650766) are gratefully acknowledged for support.
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S-(4-Methoxyphenyl) Benzothioate (3j)
White solid; yield: 23.1 mg (94%).
Supporting Information
1H NMR (500 MHz, CDCl3):  = 8.06–7.99 (m, 2 H), 7.60 (t, J = 7.4 Hz, 1
H), 7.48 (t, J = 7.7 Hz, 2 H), 7.42 (d, J = 8.8 Hz, 2 H), 6.99 (d, J = 8.8 Hz, 2
H), 3.85 (s, 3 H).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690055.
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13C NMR (126 MHz, CDCl3):  = 191.37, 161.15, 137.03, 136.97,
133.89, 129.05, 127.80, 118.25, 115.32, 55.73.
References
S-[4-(Trifluoromethyl)phenyl] Benzothioate (3k)
(1) (a) Greenberg, A.; Breneman, C. M.; Liebman, J. F. The Amide
White solid; yield: 23.7 mg (84%).
1H NMR (500 MHz, CDCl3):  = 8.03 (d, J = 7.4 Hz, 2 H), 7.71 (d, J = 8.2
Hz, 2 H), 7.67–7.62 (m, 3 H), 7.51 (t, J = 7.8 Hz, 2 H).
13C NMR (126 MHz, CDCl3):  = 189.24, 136.60, 135.56, 134.39,
132.54, 131.81 (q, JC–F = 32.9 Hz), 129.24, 127.92, 126.34 (q, JC–F = 3.7
Hz), 124.17 (q, JC–F = 274.6 Hz).
Linkage: Structural Significance in Chemistry, Biochemistry and
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(2) (a) Larock, R. C. Comprehensive Organic Transformations; John
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19F NMR (471 MHz, CDCl3):  = –62.85.
S-(4-Fluorophenyl) Benzothioate (3l)
White solid; yield: 20.1 mg (86%).
1H NMR (500 MHz, CDCl3):  = 8.05–7.99 (m, 2 H), 7.62 (t, J = 7.4 Hz, 1
H), 7.52–7.47 (m, 4 H), 7.20–7.12 (m, 2 H).
13C NMR (126 MHz, CDCl3):  = 190.44, 164.00 (d, JC–F = 250.6 Hz),
137.50 (d, JC–F = 8.6 Hz), 136.77, 134.14, 129.15, 127.85, 122.98 (d,
JC–F = 3.5 Hz), 116.89 (d, JC–F = 22.0 Hz).
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19F NMR (471 MHz, CDCl3):  = –111.09.
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S-(o-Tolyl) Benzothioate (3m)
Colorless oil; yield: 21.0 mg (92%).
1H NMR (500 MHz, CDCl3):  = 8.10–8.02 (m, 2 H), 7.62 (t, J = 7.4 Hz, 1
H), 7.52–7.48 (m, 3 H), 7.41–7.35 (m, 2 H), 7.30–7.26 (m, 1 H), 2.41 (s,
3 H).
13C NMR (126 MHz, CDCl3):  = 189.96, 143.00, 137.16, 136.75,
133.90, 131.17, 130.56, 129.07, 127.89, 127.16, 127.01, 21.15.
S-Decyl Benzothioate (3n)
Yellow oil; yield: 26.6 mg (96%).
1H NMR (500 MHz, CDCl3):  = 8.01–7.93 (m, 2 H), 7.55 (t, J = 7.4 Hz, 1
H), 7.44 (t, J = 7.7 Hz, 2 H), 3.07 (t, J = 7.4 Hz, 2 H), 1.71–1.64 (m, 2 H),
1.46–1.39 (m, 2 H), 1.35–1.24 (m, 12 H), 0.88 (t, J = 6.9 Hz, 3 H).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

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Md. M. Rahman et al.
Paper
Synthesis
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G