CuI-Catalyzed Decarboxylative Thiolation of Propargylic Cyclic Carbonates/Carbamates to Access Allenyl Thioethers

Article abstract of DOI:10.1021/acs.joc.1c00453

The first CuI-catalyzed decarboxylative thiolation of terminal alkyne-substituted cyclic carbonates/carbamates to access allenes has been developed. A wide range of hydroxymethyl-and aminomethyl-containing allenyl thioethers were smoothly obtained in good to excellent yields under mild conditions. The copper-allenylidene intermediate among the process is crucial to the decarboxylative thiolation reaction. This method opens up a new channel to access allenyl thioether compounds.

Full text of DOI:10.1021/acs.joc.1c00453

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Article
CuI-Catalyzed Decarboxylative Thiolation of Propargylic Cyclic
Carbonates/Carbamates to Access Allenyl Thioethers
Wen-Ya Lu, Yong You,* Ting-Ting Li, Zhen-Hua Wang, Jian-Qiang Zhao, and Wei-Cheng Yuan*
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ABSTRACT: The first CuI-catalyzed decarboxylative thiolation of
terminal alkyne-substituted cyclic carbonates/carbamates to access allenes
has been developed. A wide range of hydroxymethyl- and aminomethyl-
containing allenyl thioethers were smoothly obtained in good to excellent
yields under mild conditions. The copper-allenylidene intermediate among
the process is crucial to the decarboxylative thiolation reaction. This
method opens up a new channel to access allenyl thioether compounds.
copper-allenylidene intermediate for the synthesis of allenes
has not been achieved. Moreover, we also noticed that, to date,
there are only three reports about the conversion from
nonterminal alkyne-substituted cyclic carbonates to allenes
catalyzed by copper salts (Scheme 1, previous work B).10
Among them, only one terminal alkyne-substituted cyclic
carbonate substrate was investigated to access three different
α-hydroxyallene products in Woodward and Krause’s report.10a
Inspired by these existing reports on the reactions involving
terminal alkyne-substituted cyclic carbonates and the prom-
inent reactivity of the copper-allenylidene intermediates Int 1,
we speculated that the propargylic cyclic carbonates 1 should
also be applicable to the decarboxylative nucleophilic
substitution, thus allowing to access allenes.
INTRODUCTION
■
Allenes and their derivatives are particularly important as
synthetic precursors in the synthesis of many structurally
interesting and medicinally useful compounds.1 A large
number of elegant strategies have been developed toward the
construction of diverse allenes over the past couple of
decades.2,3 Among the various types of allenyl compounds,
allenyl thioethers have been proved to be a particular type of
versatile building blocks for the formation of more complex
structures in organic synthesis.4 Along this line, it will evoke
strong demands for the creative methods to access structurally
diverse allenyl thioethers and their further synthetic utilization.
Although immense efforts have been made on the synthesis of
various allenes from many synthetic organic chemistry
communities, the research concerning the preparation of
allenyl thioethers, in particular, through a simple and effective
approach, is relatively underdeveloped.5 In this context, the
development of a general and robust protocol to access the
important allenyl thioether scaffolds would be highly desirable.
It is well-known that the transition-metal-catalyzed nucleo-
philic substitution of propargylic electrophiles with different
nucleophiles has become one of the powerful strategies for the
synthesis of allenes.6 In this research area, a variety of
propargylic electrophiles have been designed and utilized in
different types of reactions to access allenes. Among the diverse
propargylic electrophiles, the propargylic cyclic carbonates 1
(Scheme 1) can be conveniently prepared from 2-hydroxy-
acetophenones and have been successfully used in copper-
catalyzed decarboxylative propargylic substitution reactions7
and decarboxylative cyclization reactions (Scheme 1, previous
work A).8 In particular, it is worth noting that the generation of
copper-allenylidene intermediates Int 1 (Scheme 1) from
copper-catalyzed decarboxylation in the process is crucial to
these transformations since the intermediates Int 1 are very
liable to be attacked by nucleophilic reagents.9 Despite these
advances, we noticed that the application of this type of
terminal alkyne-substituted cyclic carbonates 1 through a
Given the fundamental importance of allenyl thioethers4 and
our continued interest in metal-catalyzed decarboxylative
transformations,8c herein, we report the first copper-catalyzed
decarboxylative thiolation of terminal alkyne-substituted cyclic
carbonates 1 via copper-allenylidene intermediates Int 1 for
the synthesis of a series of hydroxymethyl-containing
trisubstituted allenyl thioethers (Scheme 1). We also
demonstrated that the same catalytic system could be extended
to terminal alkyne-substituted cyclic carbamates 1′ for
accessing structurally diverse aminomethyl-containing trisub-
stituted allenyl thioethers (Scheme 1).
RESULTS AND DISCUSSION
■
We began our studies with the reaction of propargylic cyclic
carbonate 1a and phenylmethanethiol 2a for the screening of
Received: February 23, 2021
Published: April 12, 2021
https://doi.org/10.1021/acs.joc.1c00453
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 6711−6720
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Scheme 1. Reactions of Propargylic Cyclic Carbonates/Carbamates Catalyzed by Copper Salts
a
reaction parameters. As shown in Table 1, after a systematic
investigation of several conditions, we finally confirmed that
allenyl thioether 3a could be obtained in 99% yield under the
optimal conditions by using 10 mol % of CuI as the catalyst
and diisopropylethylamine (DIPEA) as a base in CH2Cl2 at
reflux temperature for 15 h (entry 1). Any variation from the
optimal conditions would result in a lower yield. In the absence
of CuI, only a trace amount of 3a was observed (entry 2).
Replacing the CuI with Cu(OTf)2 or [Cu(CH3CN)4]PF6 led
to a significant decrease in yield (entries 3 and 4). The reaction
did not occur without the base DIPEA (entry 5). Nevertheless,
the replacement of DIPEA with other bases such as DMAP,
DABCO, and Cs2CO3 resulted in decreased yields (entries 6−
8). Comparing the reaction in solvents such as CHCl3, THF,
and toluene with that in CH2Cl2, it was found that CH2Cl2 is
the best choice for the reaction (entries 9−11 vs entry 1).
Lowering the catalyst loading to 5 mol %, the reaction gave a
decreased yield (entry 12). With 0.5 equiv of DIPEA for the
reaction, the yield of 3a was reduced to 81% (entry 13).
With the optimal reaction conditions in hand, the reaction
scope with respect to the propargylic cyclic carbonates 1 was
examined by reacting with phenylmethanethiol 2a (Scheme 2).
Different electron-donating groups (Me-, MeO-, tBu-)
incorporated on the phenyl ring of cyclic carbonate partners,
regardless of their substitution position, could be tolerated well
in the reaction with 2a to generate the allenyl thioethers 3b−g
in 82−91% yields. Similarly, several electron-withdrawing
Table 1. Optimization of Reaction Conditions
b
entry
variation from the “standard” conditions
yield (%)
1
none
99(90)
trace
82
84
nr
53
83
48
52
2
no CuI
3
4
5
Cu(OTf)2 instead of CuI
[Cu(CH3CN)4]PF6 instead of CuI
no DIPEA
6
7
8
9
10
11
12
13
DMAP instead of DIPEA
DABCO instead of DIPEA
Cs2CO3 instead of DIPEA
CHCl3 instead of CH2Cl2
THF instead of CH2Cl2
toluene instead of CH2Cl2
5 mol % of CuI
65
trace
83
0.5 equiv of DIPEA
81
a
Reactions were carried out on a 0.2 mmol scale in 1.0 mL of the
b
solvent at 40 °C for 15 h. NMR yield of 3a with dibromomethane as
an internal standard. Isolated yield in parentheses. DMAP = 4-
Dimethylaminopyridine, DABCO = 1,4-diazabicyclo[2.2.2]octane,
THF = tetrahydrofuran, nr = no reaction.
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Scheme 2. Substrate Scope of Propargylic Cyclic Carbonates
1
Scheme 3. Substrate Scope of Various Thiolation Reagents
2
a
a
Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmol), CuI (10 mol %),
and DIPEA (1.0 equiv) in 1.0 mL of CH2Cl2 were heated to reflux for
b
15 h. Yields are isolated yields. The reaction was carried out at room
temperature for 1.0 h.
reaction with 1a under the standard conditions, the product
3a′ also could be obtained in 42% yield by prolonging the
reaction time to 60 h. Meanwhile, ethyl thioglycolate was able
to react smoothly with 1a under the standard conditions to
furnish 3b′ in 76% yield. Ultimately, the structure of product
3v was confirmed by X-ray crystallographic analysis and is
shown in Scheme 3.11
a
Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), CuI (10 mol %),
and DIPEA (1.0 equiv) in 1.0 mL of CH2Cl2 was heated to reflux for
15 h. Yields are isolated yields.
Then, we turned our attention toward exploring the
analogous decarboxylative thiolation of propargylic cyclic
carbamates 4 to prepare the nitrogen-containing allenyl
thioether compounds (Scheme 4). To our delight, under the
standard conditions, phenyl-substituted propargylic cyclic
carbamate 4a smoothly reacted with phenylmethanethiol 2a
to give 5a in 97% yield. Nevertheless, diverse propargylic cyclic
carbamates containing electron-donating or electron-with-
drawing substituents in ortho-, meta-, and para-positions were
tolerated well to the conditions, giving the desired allenyl
thioethers 5b−h in good yields. Sterically demanding α-
naphthyl-derived propargylic cyclic carbamate also worked well
to produce the corresponding product 5i in 72% yield. We also
found that the methylsulfonyl as the nitrogen-protecting group
was tolerated well under the current system, providing 5j in
90% yield. On the other hand, we also found that the thiolation
reagents bearing electron-donating or electron-withdrawing
substituents could smoothly react with 4a in this procedure
and gave the desired 5k and 5l in acceptable yields. Ultimately,
the benzyl-substituted propargylic cyclic carbamate (R1 = Bn)
was subjected to the reaction but without reactivity,
presumably due to the low reactivity.
groups, including F-, Cl-, and Br- in the ortho-, meta-, or para-
position, were also tolerated, and the corresponding products
3h−o could be obtained in good to excellent yields.
Additionally, the bulker α-naphthyl-substituted substrate was
suitable for the formation of the target compound 3p in 79%
yield. However, the propargylic cyclic carbonate bearing an
aliphatic group (R1 = Me) had no reaction under the standard
conditions, probably due to the low reactivity.
We further investigated the substrate scope of the reaction
by varying the thiolation reagent partners (Scheme 3). Under
the standard conditions, the methyl- or chlorine-substituted
phenylmethanethiols, regardless of the substitution in the
ortho-, meta-, or para-position of the benzene ring, could
successfully participate in the decarboxylative thiolation by
reacting with 1a, furnishing the products 3q−v in good yields.
Moreover, benzenethiol as a substrate also could react with 1a
and led to the formation of 3w in 42% yield. Nevertheless, the
heterocyclic aromatic substrate benzo[d]thiazole-2-thiol was
able to smoothly deliver product 3x in 73% yield. Both 4-
methoxybenzenethiol and 4-chlorobenzenethiol were able to
react with 1a at room temperature, furnishing the correspond-
ing product 3y in 50% yield and 3z in 56% yield, respectively.
In addition, employing the aliphatic thiol as a substrate for the
To examine the synthetic potential of the present strategy, a
gram-scale reaction of compounds 4a and 2a was carried out
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5b).12 The thioether moiety could be oxidized to the sulfone
unit of compounds 6 by 3-chloroperbenzoic acid. Since the
benzylthio substituent may serve as a good leaving group, in
the presence of boron trifluoride etherate, the intramolecular
cyclization of 5a gave rise to the elimination of sulfur moiety
and afforded the 3-phenylpyrrole 7 in 73% yield.4b When 5a
was treated with iodine in the mixture of acetone and water at
room temperature, the cascade cyclization−elimination process
led to the substituted pyrrole 8 in 39% yield.4c Similarly, the
selenium-containing pyrrole derivative 9 could be obtained in
63% yield when treating 5a with phenylselenyl chloride.13 To
our delight, we also developed a one-pot reaction protocol for
the synthesis of 7 from 4a and 2a (Scheme 5c).12 After the
reaction of 4a and 2a under the standard decarboxylative
thiolation conditions and without workup, the mixture was
subsequently treated with boron trifluoride etherate at room
temperature to give compound 7 in 57% yield through the two
steps in one-pot reaction procedure (Scheme 5c).
Scheme 4. Substrate Scope of Decarboxylative Thiolation
Reaction of Propargylic Cyclic Carbamates
a
To obtain insight into the possible mechanism of the
decarboxylative thiolation reaction, several control experiments
were carried out under the standard conditions (Scheme 6).
Scheme 6. Control Experiments
a
Reaction conditions: 4 (0.2 mmol), 2 (0.4 mmol), CuI (10 mol %),
and DIPEA (1.0 equiv) in 1.0 mL of CH2Cl2 was heated to reflux for
15 h. Yields are isolated yields.
under the standard conditions. The corresponding product 5a
was obtained in 88% isolated yield, which indicated a good
practical utility of the method (Scheme 5a).12
To further demonstrate the utility of this CuI-catalyzed
decarboxylative thiolation, some synthetic transformations of
the allenyl thioether product 5a were carried out (Scheme
The terminal alkyne-substituted cyclic carbonate substrate 1a
could smoothly react with 2a to yield the desired allenyl
thioethers 3a. However, when the nonterminal alkyne-
substituted cyclic carbonate substrates (R = Ph, cyclopropyl)
were tested, no reaction was observed (Scheme 6). These
control reactions indicated that the terminal alkyne moiety in
the cyclic carbonate substrate is vital for the formation of
copper-allenylidene intermediates.
Scheme 5. Gram-Scale Reaction, Transformations of 5a, and
One-Pot Reaction for the Synthesis of Compound 7
Based on our experimental outcomes and previous related
studies on the copper-catalyzed decarboxylative substitution
reaction,7,8 a plausible mechanism is proposed in Scheme 7. In
the presence of CuI, the terminal alkyne moiety of substrate 1
is activated by forming a Cu-alkyne π-complex I. And then,
with the base-assisted deprotonation, a copper-acetylide
species II is generated. Subsequently, the species II undergoes
decarboxylation and protonation to furnish the copper-
allenylidene ion intermediate Int 1, which is in resonance
with its copper-acetylide ion intermediate Int 1′. Under the
basic condition, the phenylmethanethiolate is in situ generated
from phenylmethanethiol 2 and further nucleophilic attacks
the α-position of intermediate Int 1 to form copper-allene
species III. Finally, the allenyl organocopper intermediates III
undergo a protonation−demetalation process to yield the
target product 3 and turn the copper catalyst over to the next
catalytic cycle.
CONCLUSION
■
In summary, we have developed a CuI-catalyzed decarbox-
ylative thiolation reaction of propargylic cyclic carbonates and
propargylic cyclic carbamates. With the developed protocol, a
wide range of hydroxymethyl- and aminomethyl-containing
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HRMS (ESI) m/z [M + Na]+ calcd for C17H16NaOS 291.0820, found
291.0817.
Scheme 7. Proposed Reaction Mechanism
4-(Benzylthio)-2-(m-tolyl)buta-2,3-dien-1-ol (3b): yellow oil; 51.7
1
mg, 91% yield; eluent, PE/EA = 10:1; H NMR (300 MHz, DMSO-
d6) δ 7.34−7.15 (m, 6H), 7.11−7.00 (m, 3H), 6.46 (s, 1H), 5.14 (s,
1H), 4.39−4.22 (m, 2H), 3.92 (d, J = 13.3 Hz, 1H), 3.84 (d, J = 13.3
Hz, 1H), 2.25 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
200.4, 137.9, 137.4, 134.4, 128.9, 128.34, 128.3, 127.9, 127.0, 126.9,
123.6, 111.9, 91.3, 60.4, 35.8, 21.2; HRMS (ESI) m/z [M + K]+ calcd
for C18H18KOS 321.0710, found 321.0706.
4-(Benzylthio)-2-(p-tolyl)buta-2,3-dien-1-ol (3c): yellow oil; 49.9
1
mg, 88% yield; eluent, PE/EA = 10:1; H NMR (300 MHz, DMSO-
d6) δ 7.34−7.22 (m, 5H), 7.17 (d, J = 8.2 Hz, 2H), 7.11 (d, J = 8.1
Hz, 2H), 6.44 (s, 1H), 5.15 (t, J = 5.7 Hz, 1H), 4.38−4.25 (m, 2H),
3.91 (d, J = 13.2 Hz, 1H), 3.84 (d, J = 13.2 Hz, 1H), 2.28 (s, 3H);
13C{1H} NMR (101 MHz, DMSO-d6) δ 200.3, 137.9, 136.6, 131.5,
129.0, 128.9, 128.4, 127.0, 126.4, 111.6, 91.3, 60.4, 36.0, 20.8; HRMS
(ESI) m/z [M + Na]+ calcd for C18H18NaOS 305.0971, found
305.0977.
4-(Benzylthio)-2-(2-methoxyphenyl)buta-2,3-dien-1-ol (3d): yel-
1
low oil; 49.2 mg, 82% yield; eluent, PE/EA = 10:1; H NMR (300
MHz, DMSO-d6) δ 7.44−7.32 (m, 2H), 7.31−7.20 (m, 4H), 7.17 (m,
1H), 6.99 (d, J = 8.2 Hz, 1H), 6.94−6.81 (m, 1H), 6.18 (t, J = 2.3 Hz,
1H), 5.00 (t, J = 6.0 Hz, 1H), 4.24 (m, 2H), 3.92 (s, 1H), 3.91 (s,
1H), 3.74 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 200.7,
156.7, 137.9, 129.6, 128.9, 128.8, 128.4, 127.0, 123.9, 120.4, 111.5,
110.2, 88.8, 61.8, 55.5, 35.8; HRMS (ESI) m/z [M + K]+ calcd for
C18H18KO2S 337.0659, found 337.0670.
allenyl thioethers are able to be smoothly obtained in good to
excellent yields under mild conditions. The copper-allenyli-
denes, generated through copper-catalyzed decarboxylation,
should act as the key intermediates and undergo the
nucleophilic addition by the thiolation reagents to form allenyl
thioethers. The protocol is also operationally simple and
potentially useful for organic synthesis. The methodology
represents the first successful example of the transformation of
terminal alkyne-substituted cyclic carbonates/carbamates into
allenes. This method opens up a new channel for the synthesis
of allenyl thioether compounds. Further efforts will be devoted
to developing a catalytic asymmetric version of this reaction.
4-(Benzylthio)-2-(3-methoxyphenyl)buta-2,3-dien-1-ol (3e): yel-
1
low oil; 49.9 mg, 84% yield; eluent, PE/EA = 10:1; H NMR (300
MHz, DMSO-d6) δ 7.34−7.16 (m, 6H), 6.89−6.76 (m, 3H), 6.48 (s,
1H), 5.16 (t, J = 5.8 Hz, 1H), 4.31 (m, 2H), 3.92 (d, J = 13.3 Hz,
1H), 3.84 (d, J = 13.3 Hz, 1H), 3.71 (s, 3H); 13C{1H} NMR (101
MHz, DMSO-d6) δ 200.4, 159.3, 137.8, 136.0, 129.4, 128.9, 128.4,
127.0, 119.0, 112.6, 112.1, 111.8, 91.5, 60.4, 55.0, 35.9; HRMS (ESI)
m/z [M + K]+ calcd for C18H18KO2S 337.0659, found 337.0662.
4-(Benzylthio)-2-(4-methoxyphenyl)buta-2,3-dien-1-ol (3f): yel-
1
low oil; 48.8 mg, 82% yield; eluent, PE/EA = 10:1; H NMR (300
EXPERIMENTAL SECTION
General Methods. Reagents were purchased from commercial
■
MHz, DMSO-d6) δ 7.34−7.17 (m, 7H), 6.87 (d, J = 8.5 Hz, 2H), 6.41
(s, 1H), 5.14 (br s, 1H), 4.42−4.20 (m, 2H), 3.91 (d, J = 13.4 Hz,
1H), 3.83 (d, J = 13.4 Hz, 1H), 3.74 (s, 3H); 13C{1H} NMR (151
MHz, DMSO-d6) δ 200.1, 158.6, 138.0, 129.0, 128.4, 127.7, 127.0,
126.5, 113.9, 111.4, 91.2, 60.5, 55.2, 35.9; HRMS (ESI) m/z [M +
K]+ calcd for C18H18KO2S 337.0659, found 337.0653.
sources and were used as received unless mentioned otherwise.
1
Reactions were monitored by TLC. H NMR and 13C NMR spectra
were recorded in CDCl3 and DMSO-d6. 1H NMR chemical shifts are
reported in ppm relative to tetramethylsilane (TMS) with the solvent
resonance employed as the internal standard (CDCl3 at 7.26 ppm,
DMSO-d6 at 2.50 ppm). Data are reported as follows: chemical shift,
multiplicity (s = singlet, br s = broad singlet, d = doublet, t = triplet, q
= quartet, m = multiplet), coupling constants (Hz), and integration.
13C NMR chemical shifts are reported in ppm from tetramethylsilane
(TMS) with the solvent resonance as the internal standard (CDCl3 at
77.16 ppm, DMSO-d6 at 39.52 ppm). Melting points products were
4-(Benzylthio)-2-(4-(tert-butyl)phenyl)buta-2,3-dien-1-ol (3g):
yellow oil; 53.5 mg, 83% yield; eluent, PE/EA = 10:1; 1H NMR
(300 MHz, DMSO-d6) δ 7.38−7.27 (m, 4H), 7.27−7.17 (m, 5H),
6.43 (s, 1H), 5.12 (t, J = 5.8 Hz, 1H), 4.39−4.27 (m, 2H), 3.91 (d, J =
13.3 Hz, 1H), 3.84 (d, J = 13.3 Hz, 1H), 1.26 (s, 9H); 13C{1H} NMR
(151 MHz, DMSO-d6) δ 200.3, 149.8, 137.8, 131.5, 128.9, 128.4,
127.0, 126.2, 125.2, 111.7, 91.3, 60.4, 35.9, 34.3, 31.1; HRMS (ESI)
m/z [M + K]+ calcd for C21H24KOS 363.1185, found 363.1179.
4-(Benzylthio)-2-(2-fluorophenyl)buta-2,3-dien-1-ol (3h): yellow
oil; 56.4 mg, 99% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
DMSO-d6) δ 7.35−7.25 (m, 5H), 7.25−7.10 (m, 4H), 6.36 (t, J = 2.2
Hz, 1H), 5.17 (br s, 1H), 4.35−4.21 (m, 2H), 3.93 (d, J = 13.2 Hz,
1H), 3.87 (d, J = 13.2 Hz, 1H); 13C{1H} NMR (151 MHz, DMSO-
d6) δ 201.3, 159.7 (d, J = 248.4 Hz), 137.7, 129.8 (d, J = 3.3 Hz),
129.3 (d, J = 8.5 Hz), 128.9, 128.4, 127.0, 124.4 (d, J = 3.5 Hz), 122.8
(d, J = 12.0 Hz), 115.9 (d, J = 22.0 Hz), 107.3, 90.2, 61.6, 35.8;
HRMS (ESI) m/z [M + K]+ calcd for C17H15FKOS 325.0465, found
325.0476.
recorded on a Buchi Melting Point B-545. The HRMS were recorded
̈
by a Bruker microTOF-Q II mass spectrometer (Bremen, Germany).
The substrates 1,8a 2q−v,14 and 48c were prepared following the
procedures reported in literature.
General Experimental Procedures for the Synthesis of
Compounds 3 and 5. To a flame-dried reaction tube were added
CuI (0.02 mmol, 10 mol %), DIPEA (0.2 mmol, 1.0 equiv), cyclic
carbonate 1a (0.2 mmol, 1.0 equiv), and DCM (1.0 mL, 0.2 M). The
mixture was heated to reflux with an oil bath; then, phenyl-
methanethiol 2a (0.4 mmol, 2.0 equiv) was added. The reaction
solution was heated to reflux with an oil bath for 15 h. Finally, the
reaction mixture was directly purified by flash chromatography on
silica gel (PE/EA = 10:1) to give the product 3a.
4-(Benzylthio)-2-(4-fluorophenyl)buta-2,3-dien-1-ol (3i): yellow
oil; 50.0 mg, 87% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
DMSO-d6) δ 7.43−7.18 (m, 7H), 7.17−7.04 (m, 2H), 6.48 (s, 1H),
5.22 (t, J = 5.1 Hz, 1H), 4.43−4.20 (m, 2H), 3.92 (d, J = 13.3 Hz,
1H), 3.85 (d, J = 13.3 Hz, 1H); 13C{1H} NMR (151 MHz, DMSO-
d6) δ 200.5, 161.4 (d, J = 244.3 Hz), 137.9, 130.85 (d, J = 3.2 Hz),
128.9, 128.5, 128.4, 127.0, 115.3 (d, J = 21.5 Hz) 110.8, 91.6, 60.5,
4-(Benzylthio)-2-phenylbuta-2,3-dien-1-ol (3a): white solid; 48.0
1
mg, 90% yield; mp 45.9−46.3 °C; eluent, PE/EA = 10:1; H NMR
(300 MHz, DMSO-d6) δ 7.26 (m, 10H), 6.47 (s, 1H), 5.16 (t, J = 5.7
Hz, 1H), 4.41−4.25 (m, 2H), 3.92 (d, J = 13.3 Hz, 1H), 3.85 (d, J =
13.3 Hz, 1H); 13C{1H} NMR (151 MHz, DMSO-d6) δ 200.9, 138.1,
134.6, 129.1, 128.7, 128.6, 127.5, 127.2, 126.6, 111.8, 91.6, 60.4, 36.1;
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35.9; HRMS (ESI) m/z [M + K]+ calcd for C17H15FKOS 325.0465,
found 325.0472.
DMSO-d6) δ 7.35−7.17 (m, 5H), 7.16−7.05 (m, 3H), 7.02 (d, J = 6.4
Hz, 1H), 6.47 (s, 1H), 5.15 (t, J = 6.0 Hz, 1H), 4.34 (d, J = 5.6 Hz,
2H), 3.88 (d, J = 12.6 Hz, 1H), 3.80 (d, J = 13.2 Hz, 1H), 2.19 (s,
3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 200.5, 137.8, 137.5,
134.4, 129.5, 128.4, 128.3, 127.6, 127.2, 126.4, 126.0, 111.7, 91.5,
60.4, 35.8, 20.9; HRMS (ESI) m/z [M + Na]+ calcd for C18H18NaOS
305.0971, found 305.0966.
4-((4-Methylbenzyl)thio)-2-phenylbuta-2,3-dien-1-ol (3s): yellow
oil; 39.0 mg, 69% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
DMSO-d6) δ 7.34−7.24 (m, 4H), 7.24−7.13 (m, 3H), 7.06 (d, J = 7.8
Hz, 2H), 6.46 (s, 1H), 5.16 (t, J = 5.7 Hz, 1H), 4.45−4.23 (m, 2H),
3.88 (d, J = 13.1 Hz, 1H), 3.80 (d, J = 13.1 Hz, 1H), 2.26 (s, 3H);
13C{1H} NMR (151 MHz, DMSO-d6) δ 200.5, 136.1, 134.7, 134.5,
129.0, 128.8, 128.4, 127.2, 126.5, 111.6, 91.5, 60.4, 35.7, 20.8; HRMS
(ESI) m/z [M + Na]+ calcd for C18H18NaOS 305.0971, found
305.0980.
4-((2-Chlorobenzyl)thio)-2-phenylbuta-2,3-dien-1-ol (3t): yellow
oil; 40.5 mg, 67% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
DMSO-d6) δ 7.49−7.38 (m, 2H), 7.32−7.17 (m, 7H), 6.51 (s, 1H),
5.19 (t, J = 5.7 Hz, 1H), 4.45−4.23 (m, 2H), 4.01 (d, J = 13.5 Hz,
1H), 3.94 (d, J = 13.5 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-
d6) δ 200.8, 135.4, 134.3, 133.2, 131.2, 129.5, 129.0, 128.4, 127.3,
127.2, 126.4, 111.8, 91.0, 60.2, 33.8; HRMS (ESI) m/z [M + Na]+
calcd for C17H15ClNaOS 325.0424, found 325.0425.
4-((3-Chlorobenzyl)thio)-2-phenylbuta-2,3-dien-1-ol (3u): yellow
oil; 52.6 mg, 87% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
DMSO-d6) δ 7.40−7.33 (m, 1H), 7.33−7.14 (m, 8H), 6.49 (s, 1H),
5.19 (s, 1H), 4.42−4.23 (m, 2H), 3.94 (d, J = 13.8 Hz, 1H), 3.88 (d, J
= 13.8 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 200.8,
140.9, 134.2, 133.0, 130.1, 128.5, 128.4, 127.5, 127.2, 126.8, 126.3,
111.7, 91.0, 60.3, 35.2; HRMS (ESI) m/z [M + K]+ calcd for
C17H15ClKOS 341.0164, found 341.0167.
4-(Benzylthio)-2-(2-chlorophenyl)buta-2,3-dien-1-ol (3j): yellow
oil; 52.2 mg, 86% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
DMSO-d6) δ 7.51−7.42 (m, 1H), 7.41−7.18 (m, 8H), 6.32 (t, J = 2.4
Hz, 1H), 5.21 (t, J = 6.0 Hz, 1H), 4.23 (dd, J = 5.9, 2.0 Hz, 2H), 3.95
(d, J = 13.0 Hz, 1H), 3.89 (d, J = 13.0 Hz, 1H); 13C{1H} NMR (101
MHz, DMSO-d6) δ 199.7, 137.6, 134.0, 132.1, 130.6, 129.8, 129.1,
128.9, 128.4, 127.1, 127.0, 110.1, 90.7, 62.1, 36.0; HRMS (ESI) m/z
[M + K]+ calcd for C17H15ClKOS 341.0164, found 341.0163.
4-(Benzylthio)-2-(3-chlorophenyl)buta-2,3-dien-1-ol (3k): yellow
oil; 52.8 mg, 87% yield; eluent, PE/EA = 10:1; 1H NMR (400 MHz,
DMSO-d6) δ 7.34−7.16 (m, 9H), 6.56 (t, J = 2.1 Hz, 1H), 5.23 (s,
1H), 4.37−4.25 (m, 2H), 3.93 (d, J = 13.5 Hz, 1H), 3.85 (d, J = 13.5
Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 200.6, 137.7,
137.0, 133.2, 130.2, 128.8, 128.3, 127.0, 126.9, 126.0, 125.1, 110.8,
92.0, 60.3, 35.7; HRMS (ESI) m/z [M + Na]+ calcd for
C17H15ClNaOS 325.0424, found 325.0425.
4-(Benzylthio)-2-(4-chlorophenyl)buta-2,3-dien-1-ol(3l): yellow
oil; 52.7 mg, 87% yield; eluent, PE/EA = 10:1; 1H NMR (300
MHz, DMSO-d6) δ 7.43−7.14 (m, 9H), 6.51 (s, 1H), 5.22 (t, J = 5.6
Hz, 1H), 4.39−4.21 (m, 2H), 3.92 (d, J = 13.3 Hz, 1H), 3.84 (d, J =
13.3 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 200.6, 137.8,
133.5, 131.7, 128.9, 128.4, 128.3, 128.2, 127.0, 110.7, 91.8, 60.3, 35.8;
HRMS (ESI) m/z [M + K]+ calcd for C17H15ClKOS 341.0164, found
341.0172.
4-(Benzylthio)-2-(2-bromophenyl)buta-2,3-dien-1-ol (3m): yel-
1
low oil; 71.3 mg, 99% yield; eluent, PE/EA = 10:1; H NMR (300
MHz, DMSO-d6) δ 7.63 (d, J = 7.9 Hz, 1H), 7.38−7.17 (m, 8H), 6.31
(t, J = 2.2 Hz, 1H), 5.21 (t, J = 6.0 Hz, 1H), 4.20 (dd, J = 5.4, 2.0 Hz,
2H), 3.96 (d, J = 13.0 Hz, 1H), 3.89 (d, J = 13.1 Hz, 1H); 13C{1H}
NMR (101 MHz, DMSO-d6) δ 199.2, 137.6, 136.0, 132.9, 130.8,
129.3, 128.9, 128.4, 127.7, 127.1, 122.4, 111.9, 91.0, 62.1, 36.1;
HRMS (ESI) m/z [M + K]+ calcd for C17H15BrKOS 384.9659, found
384.9662.
4-(Benzylthio)-2-(3-bromophenyl)buta-2,3-dien-1-ol (3n): yellow
oil; 55.0 mg, 79% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
DMSO-d6) δ 7.45−7.36 (m, 2H), 7.34−7.18 (m, 7H), 6.55 (s, 1H),
5.27 (t, J = 5.2 Hz, 1H), 4.42−4.18 (m, 2H), 3.92 (d, J = 13.5 Hz,
1H), 3.84 (d, J = 13.5 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-
d6) δ 200.6, 137.8, 137.3, 130.5, 130.0, 128.9, 128.8, 128.4, 127.0,
125.6, 121.9, 110.8, 92.1, 60.4, 35.8; HRMS (ESI) m/z [M + K]+
calcd for C17H15BrKOS 384.9659, found 384.9657.
4-(Benzylthio)-2-(4-bromophenyl)buta-2,3-dien-1-ol (3o): yellow
oil; 61.1 mg, 89% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
DMSO-d6) δ 7.52−7.41 (m, 2H), 7.32−7.15 (m, 7H), 6.50 (s, 1H),
5.23 (br s, 1H), 4.38−4.19 (m, 2H), 3.92 (d, J = 13.3 Hz, 1H), 3.84
(d, J = 13.3 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 200.6,
137.8, 133.9, 131.3, 128.9, 128.8, 128.5, 128.4, 127.0, 120.3, 110.8,
91.9, 60.3, 35.9; HRMS (ESI) m/z [M + K]+ calcd for C17H15BrKOS
384.9659, found 384.9663.
4-(Benzylthio)-2-(4-chlorophenyl)buta-2,3-dien-1-ol (3v): white
solid; 52.0 mg, 86% yield; mp 97.6−97.8 °C; eluent, PE/EA = 10:1;
1H NMR (300 MHz, DMSO-d6) δ 7.42−7.07 (m, 9H), 6.46 (s, 1H),
5.19 (t, J = 4.8 Hz, 1H), 4.55−4.10 (m, 2H), 3.92 (d, J = 13.7 Hz,
1H), 3.86 (d, J = 13.7 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-
d6) δ 200.9, 137.2, 134.3, 131.5, 130.7, 128.3, 128.26, 127.2, 126.4,
111.6, 91.0, 60.3, 35.0. HRMS (ESI) m/z [M + Na]+ calcd for
C17H15ClNaOS 325.0424, found 325.0436.
2-Phenyl-4-(phenylthio)buta-2,3-dien-1-ol (3w): yellow oil; 21.6
1
mg, 42% yield; eluent, PE/EA = 10:1; H NMR (300 MHz, DMSO-
d6) δ 7.48−7.43 (m, 2H), 7.38−7.33 (m, 6H), 7.29−7.24 (m, 2H),
6.71 (t, J = 2.1 Hz, 1H), 5.30 (t, J = 5.8 Hz, 1H), 4.45−4.34 (m, 2H);
13C{1H} NMR (101 MHz, DMSO-d6) δ 203.8, 134.8, 133.7, 129.3,
128.9, 128.6, 127.7, 126.7, 126.5, 111.1, 89.7, 59.9; HRMS (ESI) m/z
[M + K]+ calcd for C16H14KOS 293.0397, found 293.0395.
4-(Benzo[d]thiazol-2-ylthio)-2-phenylbuta-2,3-dien-1-ol (3x):
yellow oil; 45.2 mg, 73% yield; eluent, PE/EA = 10:1; 1H NMR
(300 MHz, DMSO-d6) δ 8.08 (d, J = 7.8 Hz, 1H), 7.89 (d, J = 8.2 Hz,
1H), 7.54−7.36 (m, 6H), 7.35−7.26 (m, 1H), 7.10 (s, 1H), 5.44 (t, J
= 6.0 Hz, 1H), 4.52 (d, J = 5.5 Hz, 2H); 13C{1H} NMR (101 MHz,
DMSO-d6) δ 206.3, 166.3, 153.2, 135.0, 132.7, 128.8, 128.2, 126.9,
126.6, 124.7, 122.0, 121.5, 112.0, 86.0, 59.6; HRMS (ESI) m/z [M +
H]+ calcd for C17H14NOS2 312.0511, found 312.0514.
4-(Benzylthio)-2-(naphthalen-1-yl)buta-2,3-dien-1-ol (3p): yel-
1
low oil; 50.5 mg, 79% yield; eluent, PE/EA = 10:1; H NMR (300
MHz, DMSO-d6) δ 7.92−7.83 (m, 3H), 7.83−7.75 (m, 1H), 7.54−
7.45 (m, 2H), 7.38−7.29 (m, 3H), 7.29−7.20 (m, 3H), 6.58 (s, 1H),
5.26 (t, J = 6.0 Hz, 1H), 4.46 (m, 2H), 3.96 (d, J = 13.3 Hz, 1H), 3.88
(d, J = 13.3 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 201.2,
137.9, 133.0, 132.2, 131.8, 128.9, 128.4, 128.1, 127.8, 127.5, 127.0,
126.3, 126.1, 125.2, 124.5, 112.0, 91.9, 60.4, 35.9; HRMS (ESI) m/z
[M + Na]+ calcd for C21H18NaOS 341.0971, found 341.0970.
4-((2-Methylbenzyl)thio)-2-phenylbuta-2,3-dien-1-ol (3q): yellow
oil; 40.5 mg, 72% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
DMSO-d6) δ 7.34−7.21 (m, 6H), 7.20−7.12 (m, 3H), 6.50 (s, 1H),
5.19 (t, J = 5.1 Hz, 1H), 4.42- 4.29 (m, 2H), 3.92 (d, J = 12.8 Hz,
1H), 3.82 (d, J = 12.9 Hz, 1H), 2.29 (s, 3H); 13C{1H} NMR (101
MHz, DMSO) δ 200.5, 136.5, 135.3, 134.5, 130.3, 129.7, 128.5,
127.4, 127.3, 126.4, 125.9, 111.7, 91.5, 60.3, 34.2, 18.7; HRMS (ESI)
m/z [M + Na]+ calcd for C18H18NaOS 305.0971, found 305.0973.
4-((3-Methylbenzyl)thio)-2-phenylbuta-2,3-dien-1-ol (3r): yellow
oil; 44.4 mg, 79% yield; eluent, PE/EA = 10:1; 1H NMR (300 MHz,
4-((4-Methoxyphenyl)thio)-2-phenylbuta-2,3-dien-1-ol (3y): yel-
1
low oil, 28.7 mg, 50% yield; eluent, PE/EA = 10:1; H NMR (400
MHz, DMSO-d6) δ 7.44−7.37 (m, 2H), 7.37−7.28 (m, 4H), 7.27−
7.20 (m, 1H), 6.96−6.87 (m, 2H), 6.59 (t, J = 2.2 Hz, 1H), 5.19 (t, J
= 5.8 Hz, 1H), 4.42−4.25 (m, 2H), 3.73 (s, 3H); 13C{1H} NMR (101
MHz, DMSO-d6) δ 202.1, 159.0, 134.0, 132.7, 128.4, 127.4, 126.4,
124.0, 114.8, 111.5, 92.1, 59.9, 55.2; HRMS (ESI) m/z [M + Na]+
calcd for C17H16NaO2S 307.0763, found 307.0764.
4-((4-Chlorophenyl)thio)-2-phenylbuta-2,3-dien-1-ol (3z): yellow
1
oil, 32.1 mg, 56% yield; eluent, PE/EA = 10:1; H NMR (300 MHz,
DMSO-d6) δ 7.49−7.27 (m, 9H), 6.72 (s, 1H), 5.30 (t, J = 5.8 Hz,
1H), 4.41 (d, J = 6.1 Hz, 2H); 13C{1H} NMR (101 MHz, DMSO-d6)
δ 203.9, 133.8, 133.5, 131.3, 130.5, 129.1, 128.6, 127.6, 126.5, 111.3,
89.3, 59.7; HRMS (ESI) m/z [M + Na]+ calcd for C16H13ClNaOS
311.0268, found 311.0263.
6716
https://doi.org/10.1021/acs.joc.1c00453
J. Org. Chem. 2021, 86, 6711−6720

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
4-(Isobutylthio)-2-phenylbuta-2,3-dien-1-ol (3a′): yellow oil; 19.5
N-(4-(Benzylthio)-2-(4-chlorophenyl)buta-2,3-dien-1-yl)-4-meth-
ylbenzenesulfonamide (5f): yellow oil; 77.4 mg, 85% yield; eluent,
PE/EA = 8:1; 1H NMR (300 MHz, DMSO-d6) δ 7.94 (t, J = 6.2 Hz,
1H), 7.69 (d, J = 8.1 Hz, 2H), 7.40−7.24 (m, 7H), 7.23−7.14 (m,
4H), 6.51 (s, 1H), 3.91 (d, J = 13.4 Hz, 1H), 3.83 (d, J = 13.4 Hz,
1H), 3.80−3.73 (m, 1H), 3.68 (dd, J = 14.9, 4.3 Hz, 1H), 2.38 (s,
3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 201.1, 142.7, 137.5,
132.8, 132.0, 129.6, 128.8, 128.7, 128.4, 128.3, 128.0, 127.0, 126.6,
107.3, 93.1, 43.0, 35.5, 21.0; HRMS (ESI) m/z [M + Na]+ calcd for
C24H22ClNNaO2S2 478.0673, found 478.0669.
N-(4-(Benzylthio)-2-(3-bromophenyl)buta-2,3-dien-1-yl)-4-meth-
ylbenzenesulfonamide (5g): yellow oil; 80.7 mg, 81% yield; eluent,
PE/EA = 8:1; 1H NMR (300 MHz, DMSO-d6) δ 7.95 (t, J = 6.3 Hz,
1H), 7.67 (d, J = 8.2 Hz, 2H), 7.44−7.34 (m, 3H), 7.32−7.22 (m,
4H), 7.22−7.11 (m, 4H), 6.54 (s, 1H), 3.91 (d, J = 13.5 Hz, 1H),
3.83 (d, J = 13.6 Hz, 1H), 3.80−3.73 (m, 1H), 3.68 (dd, J = 15.9, 5.9
Hz, 1H), 2.39 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
201.1, 142.7, 137.6, 137.5, 136.5, 130.4, 130.1, 129.6, 128.8, 128.7,
128.3, 126.9, 126.6, 125.3, 121.9, 107.3, 93.2, 43.0, 35.4, 21.1; HRMS
(ESI) m/z [M + Na]+ calcd for C24H22BrNNaO2S2 522.0168, found
522.0173.
N-(4-(Benzylthio)-2-(4-bromophenyl)buta-2,3-dien-1-yl)-4-meth-
ylbenzenesulfonamide (5h): yellow oil; 84.1 mg, 84% yield; eluent,
PE/EA = 8:1; 1H NMR (300 MHz, DMSO-d6) δ 7.91 (t, J = 6.2 Hz,
1H), 7.67 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 7.37 (d, J =
8.0 Hz, 2H), 7.31−7.19 (m, 5H), 7.09 (d, J = 8.6 Hz, 2H), 6.50 (s,
1H), 3.91 (d, J = 13.3 Hz, 1H), 3.82 (d, J = 13.3 Hz, 1H), 3.79−3.71
(m, 1H), 3.66 (dd, J = 16.4, 6.3 Hz, 1H), 2.39 (s, 3H); 13C{1H} NMR
(101 MHz, DMSO-d6) δ 201.0, 142.7, 137.5, 133.2, 131.2, 129.6,
128.8, 128.4, 128.3, 127.0, 126.6, 120.6, 107.4, 93.1, 43.0, 35.5, 21.0;
HRMS (ESI) m/z [M + Na]+ calcd for C24H22BrNNaO2S2 522.0168,
found 522.0171.
1
mg, 42% yield; eluent, PE/EA = 10:1; H NMR (300 MHz, DMSO-
d6) δ 7.47−7.36 (m, 4H), 7.34−7.23 (m, 1H), 6.51 (s, 1H), 5.21 (t, J
= 5.7 Hz, 1H), 4.44 (dd, J = 5.6, 2.1 Hz, 2H), 2.53 (d, J = 6.8 Hz,
2H), 1.85−1.71 (m, 1H), 0.94 (d, J = 6.7 Hz, 3H), 0.89 (d, J = 6.6
Hz, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 199.7, 134.7,
128.5, 127.3, 126.3, 112.3, 92.3, 60.4, 28.0, 21.7, 21.6; HRMS (ESI)
m/z [M + K]+ calcd for C14H18KOS 273.0710, found 273.0714.
Ethyl 2-((4-Hydroxy-3-phenylbuta-1,2-dien-1-yl)thio)acetate
(3b′): yellow oil; 40.0 mg, 76% yield; eluent, PE/EA = 10:1; 1H
NMR (300 MHz, DMSO-d6) δ 7.44−7.29 (m, 4H), 7.30−7.19 (m,
1H), 6.51 (s, 1H), 5.15 (t, J = 5.8 Hz, 1H), 4.50−4.30 (m, 2H),
3.94−3.71 (m, 2H), 3.58 (d, J = 15.9 Hz, 1H), 3.51 (d, J = 15.9 Hz,
1H), 1.03 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (151 MHz, DMSO-d6)
δ 199.1, 169.0, 134.2, 128.4, 127.5, 126.4, 113.3, 91.6, 60.9, 60.2, 33.5,
13.9; HRMS (ESI) m/z [M + Na]+ calcd for C14H16NaO3S 287.0712,
found 287.0708.
N-(4-(Benzylthio)-2-phenylbuta-2,3-dien-1-yl)-4-methylbenzene-
sulfonamide (5a): yellow solid; 81.4 mg, 97% yield; mp 48.9−49.7
°C; eluent, PE/EA = 8:1; 1H NMR (300 MHz, DMSO-d6) δ 7.92 (t, J
= 6.1 Hz, 1H), 7.70 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H),
7.33−7.14 (m, 10H), 6.48 (s, 1H), 3.92 (d, J = 13.3 Hz, 1H), 3.83 (d,
J = 13.3 Hz, 1H), 3.79−3.74 (m, 1H), 3.69 (dd, J = 12.6, 5.9 Hz, 1H),
2.38 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 201.0, 142.7,
137.6, 133.8, 129.61, 129.6, 128.8, 128.4, 128.3, 127.4, 127.0, 126.6,
126.2, 108.1, 92.7, 43.1, 35.6, 21.0; HRMS (ESI) m/z [M + Na]+
calcd for C24H23NNaO2S2 444.1068, found 444.1061.
N-(4-(Benzylthio)-2-(m-tolyl)buta-2,3-dien-1-yl)-4-methylbenze-
nesulfonamide (5b): yellow oil; 82.7 mg, 95% yield; eluent, PE/EA =
8:1; 1H NMR (300 MHz, DMSO-d6) δ 7.91 (t, J = 6.1 Hz, 1H), 7.71
(d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.31−7.26 (m, 2H),
7.25−7.13 (m, 4H), 7.07−6.95 (m, 3H), 6.45 (s, 1H), 3.92 (d, J =
13.4 Hz, 1H), 3.83 (d, J = 13.3 Hz, 1H), 3.80−3.75 (m, 1H), 3.70
(dd, J = 14.3, 5.6 Hz, 1H), 2.38 (s, 3H), 2.23 (s, 3H); 13C{1H} NMR
(101 MHz, DMSO-d6) δ 200.8, 142.7, 137.7, 137.6, 137.5, 133.8,
129.6, 128.8, 128.3, 128.2, 126.9, 126.86, 126.7, 123.4, 108.3, 92.6,
43.1, 35.5, 26.4, 21.1, 21.0; HRMS (ESI) m/z [M + K]+ calcd for
C25H25KNO2S2 474.0964, found 474.0962.
N-(4-(Benzylthio)-2-(naphthalen-1-yl)buta-2,3-dien-1-yl)-4-
methylbenzenesulfonamide (5i): yellow oil; 68.1 mg, 72% yield;
1
eluent, PE/EA = 8:1; H NMR (300 MHz, DMSO-d6) δ 8.01 (t, J =
6.1 Hz, 1H), 7.90−7.84 (m, 1H), 7.83−7.66 (m, 5H), 7.54−7.44 (m,
2H), 7.37 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 7.5 Hz, 2H), 7.27−7.17
(m, 4H), 6.56 (s, 1H), 4.05−3.79 (m, 4H), 2.38 (s, 3H); 13C{1H}
NMR (101 MHz, DMSO-d6) δ 201.6, 142.7, 137.8, 137.6, 132.9,
132.2, 131.3, 129.6, 128.9, 128.4, 128.0, 127.8, 127.5, 127.0, 126.7,
126.4, 126.2, 125.0, 124.3, 108.5, 93.1, 43.1, 35.6, 21.0; HRMS (ESI)
m/z [M + Na]+ calcd for C28H25NNaO2S2 494.1219, found 494.1215.
N - ( 4 - ( B e n z y l t h i o ) - 2 - p h e n y l b u t a - 2 , 3 - d i e n - 1 - y l ) -
methanesulfonamide (5j): yellow solid; 62.0 mg, 90% yield; mp
69.7−70.3 °C; eluent, PE/EA = 8:1; 1H NMR (300 MHz, DMSO-d6)
δ 7.43−7.16 (m, 11H), 6.61 (s, 1H), 4.12−3.92 (m, 3H), 3.86 (d, J =
13.1 Hz, 1H), 2.93 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
200.6, 137.7, 134.0, 128.9, 128.5, 128.4, 127.5, 127.0, 126.3, 108.8,
93.3, 42.7, 39.9, 35.7; HRMS (ESI) m/z [M + Na]+ calcd for
C18H19NNaO2S2 368.0755, found 368.0740.
4-Methyl-N-(4-((4-methylbenzyl)thio)-2-phenylbuta-2,3-dien-1-
yl)benzenesulfonamide (5k): yellow oil; 77.7 mg, 89% yield; eluent,
PE/EA = 8:1; 1H NMR (300 MHz, DMSO-d6) δ 7.90 (t, J = 6.4 Hz,
1H), 7.69 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.32−7.22
(m, 3H), 7.22−7.13 (m, 4H), 7.03 (d, J = 7.8 Hz, 2H), 6.45 (s, 1H),
3.87 (d, J = 13.2 Hz, 1H), 3.84−3.63 (m, 3H), 2.39 (s, 3H), 2.24 (s,
3H); 13C{1H} NMR (151 MHz, CDCl3) δ 200.9, 142.7, 137.6, 136.1,
134.4, 133.9, 129.6, 128.9, 128.8, 128.4, 127.4, 126.6, 126.3, 108.1,
92.8, 43.1, 35.3, 21.0, 20.7; HRMS (ESI) m/z [M + Na]+ calcd for
C25H25NNaO2S2 458.1219, found 458.1198.
N-(4-(Benzylthio)-2-(p-tolyl)buta-2,3-dien-1-yl)-4-methylbenze-
nesulfonamide (5c): yellow oil; 71.0 mg, 82% yield; eluent, PE/EA =
8:1; 1H NMR (300 MHz, DMSO-d6) δ 7.89 (t, J = 6.1 Hz, 1H), 7.70
(d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.31−7.19 (m, 5H),
7.17−7.04 (m, 4H), 6.44 (s, 1H), 3.91 (d, J = 13.2 Hz, 1H), 3.81 (d, J
= 13.2 Hz, 1H), 3.79−3.70 (m, 1H), 3.65 (dd, J = 14.3, 5.9 Hz, 1H),
2.38 (s, 3H), 2.27 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
200.6, 142.7, 137.61, 137.59, 136.8, 130.9, 129.6, 129.0, 128.8, 128.4,
127.0, 126.7, 126.2, 108.1, 92.6, 43.1, 35.6, 21.0, 20.8; HRMS (ESI)
m/z [M + Na]+ calcd for C25H25NNaO2S2 458.1219, found 458.1226.
N-(4-(Benzylthio)-2-(2-methoxyphenyl)buta-2,3-dien-1-yl)-4-
methylbenzenesulfonamide (5d): yellow oil; 67.8 mg, 75% yield;
1
eluent, PE/EA = 8:1; H NMR (300 MHz, DMSO-d6) δ 7.73 (t, J =
6.3 Hz, 1H), 7.61 (d, J = 8.2 Hz, 2H), 7.39−7.19 (m, 8H), 7.01−6.89
(m, 2H), 6.89−6.80 (m, 1H), 6.17 (s, 1H), 3.98−3.81 (m, 2H),
3.80−3.57 (m, 5H), 2.38 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-
d6) δ 200.9, 156.5, 142.5, 137.8, 137.6, 129.9, 129.5, 129.2, 128.9,
128.4, 127.0, 126.6, 123.4, 120.4, 111.5, 107.0, 90.0, 55.5, 44.6, 35.5,
21.0; HRMS (ESI) m/z [M + Na]+ calcd for C25H25NNaO3S2
474.1168, found 474.1180.
N-(4-(Benzylthio)-2-(4-(tert-butyl)phenyl)buta-2,3-dien-1-yl)-4-
methylbenzenesulfonamide (5e): yellow oil; 83.8 mg, 88% yield;
N-(4-((2-Chlorobenzyl)thio)-2-phenylbuta-2,3-dien-1-yl)-4-meth-
ylbenzenesulfonamide (5l): yellow oil; 69.8 mg, 76% yield; eluent,
PE/EA = 8:1; 1H NMR (300 MHz, DMSO-d6) δ 7.91 (t, J = 6.2 Hz,
1H), 7.68 (d, J = 8.2 Hz, 2H), 7.49−7.33 (m, 4H), 7.32−7.06 (m,
7H), 6.50 (s, 1H), 3.99 (d, J = 13.6 Hz, 1H), 3.91 (d, J = 13.6 Hz,
1H), 3.81 (dd, J = 13.5, 5.1 Hz, 1H), 3.69 (dd, J = 15.2, 5.2 Hz, 1H),
2.39 (s, 3H); 13C{1H} NMR (151 MHz, DMSO-d6) δ 201.1, 142.7,
137.5, 135.1, 133.6, 133.2, 131.0, 129.6, 129.4, 129.0, 128.4, 127.5,
127.2, 126.6, 126.2, 108.2, 92.3, 43.0, 33.5, 21.0; HRMS (ESI) m/z
[M + Na]+ calcd for C24H22ClNNaO2S2 478.0673, found 478.0665.
1
eluent, PE/EA = 8:1; H NMR (300 MHz, DMSO-d6) δ 7.88 (t, J =
6.1 Hz, 1H), 7.70 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 7.33−
7.12 (m, 9H), 6.44 (s, 1H), 3.90 (d, J = 13.2 Hz, 1H), 3.81 (d, J =
13.1 Hz, 1H), 3.79−3.73 m, 1H), 3.67 (dd, J = 15.2, 5.0 Hz, 1H),
2.38 (s, 3H), 1.26 (s, 9H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
200.6, 150.0, 142.6, 137.6, 137.5, 130.9, 129.6, 128.8, 128.3, 126.9,
126.7, 126.0, 125.2, 108.0, 92.5, 43.2, 35.5, 34.2, 31.1, 21.0; HRMS
(ESI) m/z [M + K]+ calcd for C28H31KNO2S2 516.1433, found
516.1424.
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Synthesis of Compound 6. m-Chloroperbenzoic acid (0.8
mmol, 4.0 equiv) was added portionwise to a solution of allenylic
sulfide 5a (0.2 mmol, 1.0 equiv) in DCM (2.0 mL, 0.1 M) at room
temperature with vigorous stirring. When 5a disappeared (monitored
by TLC), the reaction was quenched with NaHCO3 and extracted
with DCM. The combined organic layers were dried over Na2SO4,
filtered, and concentrated in vacuo. Then the residue was purified by
column chromatography (PE/EA = 3:1) to afford compound 6 as a
white solid (55.4 mg, 61% yield).
3-Phenyl-4-(phenylselanyl)-1-tosyl-1H-pyrrole (9): yellow oil;
28.6 mg, 63% yield; eluent, PE/EA = 30:1; H NMR (300 MHz,
1
DMSO-d6) δ 7.99 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 2.4 Hz, 1H), 7.69
(d, J = 2.4 Hz, 1H), 7.51−7.44 (m, 4H), 7.32−7.23 (m, 3H), 7.19−
7.06 (m, 5H), 2.39 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
146.0, 134.7, 132.6, 132.3, 131.0, 130.5, 129.4, 128.9, 128.3, 128.0,
127.8, 127.4, 127.2, 126.4, 119.5, 109.0, 21.2; HRMS (ESI) m/z [M +
Na]+ calcd for C23H19NNaO2SSe 476.0194, found 476.0185.
Scale-up Experiment. To a flame-dried reaction tube were added
CuI (0.25 mmol, 10 mol %), DIPEA (2.5 mmol, 1.0 equiv), cyclic
carbamate 4a (2.5 mmol, 1.0 equiv), and DCM (12.5 mL, 0.2 M).
The mixture was heated to reflux with an oil bath; then,
phenylmethanethiol 2a (5 mmol, 2.0 equiv) was added. The reaction
solution was heated to reflux with an oil bath for 24 h. Finally, the
mixture was concentrated in vacuo and purified by flash
chromatography on silica gel (PE/EA = 8:1) to give the product 5a
as a yellow solid (0.923 g, 88% yield).
N-(4-(Benzylsulfinyl)-2-phenylbuta-2,3-dien-1-yl)-4-methylben-
zenesulfonamide (6): white solid; 55.4 mg, 61% yield; mp 110.8−
1
111.6 °C eluent, PE/EA = 3:1; H NMR (300 MHz, DMSO-d6) δ
8.15 (t, J = 6.3 Hz, 1H), 7.70 (d, J = 8.1 Hz, 2H), 7.50−7.37 (m, 4H),
7.37−7.23 (m, 6H), 7.14−7.02 (m, 2H), 7.00 (s, 1H), 4.67 (d, J =
13.8 Hz, 1H), 4.61 (d, J = 13.8 Hz, 1H), 3.95 (dd, J = 15.9, 6.0 Hz,
1H), 3.69 (dd, J = 14.8, 6.0 Hz, 1H), 2.40 (s, 3H); 13C{1H} NMR
(151 MHz, DMSO-d6) δ 207.0, 142.9, 137.5, 131.3, 130.7, 129.7,
128.9, 128.8, 128.7, 128.5, 126.7, 126.6, 111.8, 101.6, 60.5, 41.9, 21.1;
HRMS (ESI) m/z [M + Na]+ calcd for C24H23NNaO4S2 476.0961,
found 476.0950.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00453.
■
sı
Synthesis of Compound 7. BF3·OEt2 (20 mol %) was added to a
solution of allenylic sulfide 5a (0.2 mmol, 1.0 equiv) in DCM (1.0
mL, 0.2 M) at room temperature. The mixture stirred for 30 min, and
5a disappeared (monitored by TLC). The reaction was quenched
with NH4Cl extracted with DCM. The combined organic layers were
dried over Na2SO4, filtered, and concentrated in vacuo. Then the
residue was purified by column chromatography (PE/EA = 30:1) to
afford compound 7 as a white solid (43.6 mg, 73% yield).
One-Pot Synthetic Reaction of Compound 7. To a flame-
dried reaction tube were added CuI (0.02 mmol, 10 mol %), DIPEA
(0.2 mmol, 1.0 equiv), cyclic carbamate 5a (0.2 mmol, 1.0 equiv), and
DCM (1.0 mL, 0.2 M). The mixture was heated to reflux with an oil
bath, and then, phenylmethanethiol 2a (0.4 mmol, 2.0 equiv) was
added. The reaction solution was heated to reflux with an oil bath for
15 h. Then BF3·OEt2 (20 mol %) was added to the reaction mixture,
and the mixture was stirred for 30 min, quenched with NH4Cl, and
extracted with DCM. The combined organic layers were dried over
Na2SO4, filtered, and concentrated in vacuo. Then the residue was
purified by column chromatography (PE/EA = 30:1) to afford
compound 7 as a white solid (33.8 mg, 57% yield).
3-Phenyl-1-tosyl-1H-pyrrole (7): white solid; mp 134.8−136.1 °C,
eluent, PE/EA = 30:1; 1H NMR (300 MHz, DMSO-d6) δ 7.91 (d, J =
8.4 Hz, 2H), 7.86−7.77 (m, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.51−7.28
(m, 5H), 7.27−7.15 (m, 1H), 6.88−6.75 (m, 1H), 2.36 (s, 3H);
13C{1H} NMR (151 MHz, DMSO-d6) δ 145.5, 135.2, 132.9, 130.3,
128.9, 128.8, 127.0, 126.9, 125.4, 122.2, 116.9, 112.2, 21.1; HRMS
(ESI) m/z [M + Na]+ calcd for C17H15NNaO2S 320.0716, found
320.0726.
Copies of 1H and 13C NMR spectra data for all
compounds; single-crystal X-ray crystallography data for
3v (PDF)
Accession Codes
CCDC 2055378 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Yong You − Institute for Advanced Study, Chengdu University,
Chengdu 610106, China; Email: youyong@cdu.edu.cn
Wei-Cheng Yuan − National Engineering Research Center of
Chiral Drugs, Chengdu Institute of Organic Chemistry,
Chinese Academy of Sciences, Chengdu 610041, China;
Institute for Advanced Study, Chengdu University, Chengdu
610106, China; University of Chinese Academy of Sciences,
Beijing 100049, China; orcid.org/0000-0003-4850-
8981; Email: yuanwc@cioc.ac.cn
Synthesis of Compound 8. A solution of allenylic sulfide 5a (0.4
mmol, 1.0 equiv) in 1 mL of acetone was added slowly to a solution of
iodine (1.0 mmol, 2.5 equiv) in acetone (7 mL) and water (2 mL).
After being stirred at room temperature for about 12 h, a saturated
aqueous solution of Na2S2O3 was added. The mixture was extracted
with DCM and dried over MgSO4. Evaporation and column
chromatography on silica gel (PE/EA = 30:1) afforded 8 as a white
solid (65.6 mg, 39% yield).
3-Iodo-4-phenyl-1-tosyl-1H-pyrrole (8): yellow oil; 65.6 mg, 39%
yield; eluent, PE/EA = 30:1; 1H NMR (300 MHz, DMSO-d6) δ 7.97
(d, J = 8.3 Hz, 2H), 7.68 (d, J = 2.5 Hz, 1H), 7.57 (d, J = 2.4 Hz, 1H),
7.51−7.29 (m, 7H), 2.35 (s, 3H); 13C{1H} NMR (151 MHz, DMSO-
d6) δ 145.9, 134.6, 132.8, 130.6, 130.4, 128.4, 128.2, 127.6, 127.3,
126.1, 118.7, 71.2, 21.1; HRMS (ESI) m/z [M + Na]+ calcd for
C17H14INNaO2S 445.9682, found 445.9692.
Synthesis of Compound 9. To a solution of PhSeCl (0.15
mmol, 1.5 equiv) in 2 mL of MeCN and 0.1 mL of H2O was added 5a
(0.1 mmol, 1.0 equiv), and the mixture was stirred at room
temperature for 30 min. After complete consumption of the starting
material as monitored by TLC, the mixture was concentrated in
vacuo, and flash chromatography on silica gel (PE/EA = 30:1)
afforded 9 (28.6 mg, 63%) as an oil.
Authors
Wen-Ya Lu − National Engineering Research Center of Chiral
Drugs, Chengdu Institute of Organic Chemistry, Chinese
Academy of Sciences, Chengdu 610041, China; Institute for
Advanced Study, Chengdu University, Chengdu 610106,
China; University of Chinese Academy of Sciences, Beijing
100049, China
Ting-Ting Li − National Engineering Research Center of
Chiral Drugs, Chengdu Institute of Organic Chemistry,
Chinese Academy of Sciences, Chengdu 610041, China;
Institute for Advanced Study, Chengdu University, Chengdu
610106, China; University of Chinese Academy of Sciences,
Beijing 100049, China
Zhen-Hua Wang − Institute for Advanced Study, Chengdu
University, Chengdu 610106, China; orcid.org/0000-
0002-0603-707X
Jian-Qiang Zhao − Institute for Advanced Study, Chengdu
University, Chengdu 610106, China; orcid.org/0000-
0002-4444-9630
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Carbene Transfer Reaction. Org. Lett. 2020, 22, 7300. (g) Zhu, Y.;
Chen, F.; Cheng, D.; Chen, Y.; Zhao, X.; Wei, W.; Lu, Y.; Zhao, J.
Rhodium(III)-Catalyzed Alkenyl C-H Functionalization to Dienes
and Allenes. Org. Lett. 2020, 22, 8786. (h) Wang, H.; Luo, H.; Zhang,
Z.-M.; Zheng, W.-F.; Yin, Y.; Qian, H.; Zhang, J.; Ma, S. Pd-Catalyzed
Enantioselective Synthesis of Trisubstituted Allenes via Coupling of
Propargylic Benzoates with Organoboronic Acids. J. Am. Chem. Soc.
2020, 142, 9763.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00453
Author Contributions
All authors have given approval to the final version of the
manuscript.
Notes
(4) For selected examples on the synthetic application of allenyl
thioethers, see: (a) Tseng, H.-R.; Luh, T.-Y. Novel Coupling
Reactions of Dithioacetals with Organocuprate Reagents. Propargylic
Dithioacetal as an Allene-1,3-Zwitterion Synthon. J. Org. Chem. 1997,
62, 4568. (b) Lee, C.-F.; Yang, L.-M.; Hwu, T.-Y.; Feng, A.-S.; Tseng,
J.-C.; Luh, T.-Y. One-Pot Synthesis of Substituted Furans and
Pyrroles from Propargylic Dithioacetals. New Annulation Route to
Highly Photoluminescent Oligoaryls. J. Am. Chem. Soc. 2000, 122,
4992. (c) Ma, S.; Hao, X.; Huang, X. Reversed Stereoselectivity in
Iodohydroxylation of Allenyl Sulfides. An Efficient Synthesis of (Z)-3-
Organosulfur-2-iodo-2-propenols. Org. Lett. 2003, 5, 1217. (d) Ma, S.;
Hao, X.; Meng, X.; Huang, X. Studies on the Regio- and
Stereoselectivity of Halohydroxylation of 1,2-Allenyl Sulfides or
Selenides. J. Org. Chem. 2004, 69, 5720. (e) Dudnik, A. S.; Sromek,
A. W.; Rubina, M.; Kim, J. T.; Kel'i, A. V.; Gevorgyan, V. Metal-
Catalyzed 1,2-Shift of Diverse Migrating Groups in Allenyl Systems as
a New Paradigm toward Densely Functionalized Heterocycles. J. Am.
Chem. Soc. 2008, 130, 1440. (f) Moreno-Clavijo, E.; Carmona, A. T.;
Reissig, H.-U.; Moreno-Vargas, A. J.; Alvarez, E.; Robina, I. Allenyl
Sulfones and Allenyl Sulfides in the Synthesis of 3-Pyrrolines. A Novel
Nucleophilic [3 + 2] Cycloaddition on Allenyl Sulfones Giving
Rearranged Cycloadducts. Org. Lett. 2009, 11, 4778.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for financial support from the National Key
R&D Program of China (2018YFC0807301-3) and the NSFC
(21871252, 21801024, 21801026, and 21901024).
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