Copper-Catalyzed Sulfenylation, Sulfonylation, and Selenylation of 2,3-Allenoic Acids with Disulfides or Diselenides

Article abstract of DOI:10.1021/acs.joc.8b00858

The efficient copper-catalyzed sulfenylation and selenylation of 2,3-allenoic acids with disulfides or diselenides were developed, respectively. These reactions proceeded through tandem radical addition/intramolecular cyclization processes, affording a series of 4-sulfenylated and 4-selenylated butenolides in moderate to excellent yields. Moreover, 4-sulfonylated butenolides could also be obtained by sulfenylation of 2,3-allenoic acids and subsequent oxidation. Further transformation of the sulfur- and selenium-containing butenolides afforded the corresponding furan derivatives in good yields.

Full text of DOI:10.1021/acs.joc.8b00858

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Article
Copper-Catalyzed Sulfenylation, Sulfonylation, and Selenylation
of 2,3-Allenoic Acids with Disulfides or Diselenides
Ya-Xun Xin, Shen Pan, Yangen Huang, Xiu-Hua Xu, and Feng-Ling Qing
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00858 • Publication Date (Web): 17 May 2018
Downloaded from http://pubs.acs.org on May 17, 2018
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Page 1 of 25
The Journal of Organic Chemistry
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CopperꢀCatalyzed Sulfenylation, Sulfonylation, and
Selenylation of 2,3ꢀAllenoic Acids with Disulfides or
Diselenides
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YaꢀXun Xin,† Shen Pan,† Yangen Huang,*† XiuꢀHua Xu,*‡ and FengꢀLing Qing†,‡
† College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North
Renmin Lu, Shanghai 201620, China
‡ Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032,
China
Eꢀmail: hyg@dhu.edu.cn, xuxiuhua@sioc.ac.cn
Table of Graphic Contents
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Abstract
The efficient copperꢀcatalyzed sulfenylation and selenylation of 2,3ꢀallenoic acids with disulfides or
diselenides were developed, respectively. These reactions proceeded through tandem radical
addition/intramolecular cyclization processes, affording a series of 4ꢀsulfenylated and 4ꢀselenylated
butenolides in moderate to excellent yields. Moreover, 4ꢀsulfonylated butenolides could also be obtained
by sulfenylation of 2,3ꢀallenoic acids and subsequent oxidation. Further transformation of the sulfurꢀ
and seleniumꢀcontaining butenolides afforded the corresponding furan derivatives in good yields.
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Introduction
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Furanꢀ2(5H)ꢀones (butenolides) are an important class of compounds, which are often found in
natural products and biological compounds.1 Some representative examples of bioactive butenolides are
depicted in Figure 1. Butenolides are also important intermediate in organic synthesis,2 because of the
presence of conjugated C=C bond and fiveꢀmembered lactone ring. Consequently, the development of
synthetic strategies of butenolides has attracted enormous attention from chemists.3 On the other hand,
organosulfur compounds are significant structural motifs existing in medicinal chemistry, agrochemistry,
and material sciences.4 Therefore, a great amount of effort has been directed at the preparation of sulfurꢀ
containing butenolides, which combine the butenolide moiety with sulfurꢀcontaining group.
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Figure 1. Bioactive butenolides
Traditional approaches to sulfurꢀcontaining butenolides mainly include sulfenylation of functionalized
butenolides,5 elimination of sulfurꢀcontaining γꢀbutyrolactones,6 oxidation of sulfurꢀcontaining furans,7
reduction of sulfurꢀcontaining maleic anhydrides,8 transformation of sulfurꢀcontaining 2ꢀsilyloxyfurans,9
and cyclization of sulfurꢀcontaining building blocks.10 However, these methods suffer from the
prefunctionalized substrates. From the viewpoint of stepꢀeconomy, the methods for the simultaneous
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introduction of sulfurꢀcontaining groups and construction of butenolide moiety are more appealing. In
1997, Alper11a and Ogawa11b independently reported the Pdꢀcatalyzed carbonylative cyclization of
propargylic alcohols with carbon monoxide and disulfides or thiols to provide the corresponding 4ꢀ
sulfenylated butenolides (Scheme 1a). Afterward, Ogawa’s group realized a novel Coꢀcatalyzed
thiolative lactonization of alkynes with thiols with incorporation of two molecules of carbon monoxide
for the preparation of 5ꢀsulfenylated butenolides (Scheme 1b).12 In 2004, Ma and coꢀworkers elegantly
reported an electrophilic cyclization of 2,3ꢀallenoic acids with PhSCl (Scheme 1c).13a Recently, Christov
extended this electrophilic cyclization protocol to 2,3ꢀallenoates affording high functionalized
butenolides.13b,c More recently, the cyclization of 4ꢀmethoxyphenylꢀ3ꢀphenylpropiolate with
electrophilic sulfenylating reagents were uncovered to deliver sulfenylated spirocyclic products (Scheme
1d).14 Despite these impressive achievements, the development of new methods by thiolative cyclization
of readily available substrates to access sulfenylated butenolides is highly desirable.
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Radicalꢀtriggered cascade reactions serve as ideal strategies in the synthesis of heterocyclic scaffolds.
However, the radical cascade cyclization to access sulfenylated butenolides remains underexplored.
Recently, our group disclosed a tandem radical trifluoromethylthiolation/intramolecular cyclization of
2,3ꢀallenoic acids with AgSCF3 to afford 4ꢀtrifluoromethylthiolated butenolides.15 In continuation of our
recent research interest in organosulfur compounds15,16 and to extend the scope of radical cascade
cyclization of 2,3ꢀallenoic acids, herein we disclose a copperꢀcatalyzed sulfenylation of 2,3ꢀallenoic
acids with disulfides in the presence of (NH4)2S2O8 (Scheme 1e). It should be noted that this protocol
could be applied in the preparation of 4ꢀselenylated butenolides with diselenides as the selenylating
reagent. Furthermore, 4ꢀsulfonylated butenolides could be also obtained by sulfenylation of 2,3ꢀallenoic
acids and subsequent oxidation.
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Scheme 1. Synthesis of Sulfur-Containing Butenolides by Tandem Sulfenylation/Cyclization
Reactions
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3
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7
8
sulfenylation/carbonylative cyclization
RS
R1
R3
R1 R2
RSH
or
RSSR
Pd cat.
(a)
(b)
+
R3
+ CO
HO
90-110 oC
9
O
R2
O
O
O
(40-60 atm)
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R1
R2
R2
Co cat.
140 oC
+
+
CO
RSH
R1
(40 atm)
RS
O
electrophilic sulfenylation/cyclization
R3
R1
R3
RS
R1
R2
(c)
(d)
+
RSCl
R2
OR4
Ar
O
O
Ar
SR
MeO
+ [RS+]
O
O
O
O
O
radical sulfenylation/cyclization (this work)
RS
R1
R3
R1
R3
Cu cat.
(e)
+
RSSR
(NH4)2S2O8
R2
COOH
O
R2
O
Results and Discussion
Initially, the radical thiolative cyclization of 2ꢀmethylꢀ4ꢀphenylꢀ2,3ꢀallenoic acid (1a) was chosen as
a model reaction with 1,2ꢀdibenzyldisulfide (2a) as the sulfenylating reagent. The reaction was
performed in the presence of catalytic Cu(OAc)2 with (NH4)2S2O8 as the oxidant in CH3CN/HCO2H,
which
were
similar
to
those
previously
employed
in
the
copperꢀcatalyzed
trifluoromethylthiolation/intramolecular cyclization of 2,3ꢀallenoic acids.15 To our delight, under these
conditions the reaction afforded the desired 4ꢀbenzylsulfenyl butenolide 3a in 94% yield (Table 1, entry
1). The catalytic copper salt was crucial to this reaction. Only trace of 3a was detected without the
cooper salt (entry 2), and switching Cu(OAc)2 to CuCN or CuI led to lower yields (entries 3 and 4). The
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oxidant was also necessary for this reaction, as 3a was formed in only 8% yield in the absence of
(NH4)2S2O8 (entry 5). When K2S2O8 was used instead of (NH4)2S2O8, the reaction proceeded smoothly
to give 3a in slightly lower yield (entry 6). Being similar to the trifluoromethylthiolation of 2,3ꢀallenoic
acids,15 the use of acid as the coꢀsolvent was critical to achieve this reaction (entry 7). Using HOAc
instead of HCO2H or changing the ratio of CH3CN/HCO2H did not improve the efficiency of this
reaction (entries 8ꢀ10). Finally, decreasing the reaction temperature or shortening the reaction time led to
lower yields (entries 11 and 12).
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Table 1. Optimization of Reaction Conditionsa
entry
variant conditions
yield (%)b
1
standard conditions
without Cu(OAc)2
94
2
trace
80
3
CuCN instead of Cu(OAc)2
CuI instead of Cu(OAc)2
without (NH4)2S2O8
K2S2O8 instead of (NH4)2S2O8
without HCO2H
4
84
5
8
6
89
7
trace
62
8
HOAc instead of HCO2H
CH3CN:HCO2H = 1:1
CH3CN:HCO2H = 5:1
room temperature
9
59
10
11
12
80
67
3 h
83
aReaction conditions: 1a (0.1 mmol), BnSSBn (0.2 mmol), Cu(OAc)2 (0.02 mmol), (NH4)2S2O8 (0.2
b
mmol), CH3CN/HCO2H (1.5 mL/0.5 mL), under N2, 50 °C, 12 h. Yields were determined by 1H NMR
spectroscopy using 1,3,5ꢀtrimethylphenol as an internal standard.
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Scheme 2. Copper-Catalyzed Sulfenylation of 2,3-Allenoic Acids with Disulfidesa
1
2
3
4
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8
RS
R3
Cu(OAc)2 (0.2 eq)
(NH4)2S2O8 (2.0 eq)
R1
R2
R3
R1
R2
+
RSSR
CH3CN:HCO2H = 3:1
50 oC, 12 h
O
COOH
O
1
2
3
9
BnS
BnS
BnS
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O
O
O
O
O
O
MeO
Br
Me
3c, 86%
BnS
3b, 76%
3a, 86%
BnS
BnS
O
O
O
O
O
O
Cl
F
3e, 70%
3f, 84%
3d, 75%
BnS
BnS
BnS
O
O
O
O
O
O
F3C
3g, 70%
3h, 90%
3i, 57%
BnS
BnS
O
O
O
O
3j, 90%
3k, 90%
n-Bu S
Me S
i-Pr S
O
O
O
O
O
O
O
3n, 71%
c-Hex S
3l, 61%
3m, 64%
n-Hex S
t-Bu S
O
O
O
O
O
3q, 60%
3o, 68%
3p, 79%
aReaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), Cu(OAc)2 (0.04 mmol), (NH4)2S2O8 (0.4 mmol),
CH3CN/HCO2H (3.0 mL/1.0 mL), under N2, 50 °C, 12 h. Yields are those of the isolated products.
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With optimized conditions in hand, the substrate scope of 2,3ꢀallenoic acids and disulfides were
1
2
investigated. As shown in Scheme 2, a range of 2,3ꢀallenoic acids 1aꢀk reacted with disulfide 2a to
afford the corresponding butenolides 3aꢀk in good to excellent yields. A series of functional groups
including alkyl, alkoxy, fluoride, chloride, bromide, and trifluoromethyl were well tolerated under the
mild conditions. Satisfactorily, the 2,3ꢀallenoic acid bearing naphthyl group (1h) was also suitable for
this reaction. In the case of substrate with orthoꢀsubstitution on the benzene (1i), lower yield was
obtained. Interestingly, 2,4,4ꢀtrisubstituted 2,3ꢀallenoic acid (1j) reacted smoothly to give
polysubstituted product (2j) in 90% yield.
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Next, we examined the scope and limitation of disulfides. The reaction of 2ꢀmethylꢀ4ꢀphenylꢀ2,3ꢀ
allenoic acid (1a) and different dialkyldisulfides 2 cloud also give the desired products 3lꢀq in moderate
yields (Scheme 2). In general, the yields are lower than that of these obtained with 1,2ꢀdibenzyldisulfide
(2a) as the sulfenylating reagent, probably due to the lower stability and/or reactivity of alkylthio radical.
To our surprise, when diaryldisulfide 2h was subjected to the reaction conditions, the sulfenylated
product 3r was obtained in 33% yield along with an unexpected sulfonylated product 4a in 39% yield
(Scheme 3). The amount of sulfonylated product 4a did not change much by varying the reaction
conditions, such as the amount of (NH4)2S2O8, temperature, and reaction time.
Scheme 3. Reaction of 1a with Diaryldisulfide
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Scheme 4. Sulfonylation of 2,3-Allenoic Acidsa
1
2
3
4
5
6
7
8
ArO2S
R2
1) Cu(OAc)2 (0.2 eq)
(NH4)2S2O8 (2.0 eq)
CH3CN:HCO2H = 3:1
50 oC, 12 h
COOH
R2
R1
O
O
ArSSAr
+
2) m-CPBA (5.0 eq)
R1
CH2Cl2, rt, 2 h
1
2
4
9
O
O
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O
O
Me
S
Cl
S
O
O
O
O
4a, 88%
4b, 70%
PhO2S
PhO2S
PhO2S
O
O
O
O
O
O
Cl
4e, 75%
PhO2S n-Bu
4c, 79%
4d, 82%
PhO2S
PhO2S
O
O
O
O
O
O
F3C
Br
4g, 66%
4f, 77%
4h, 73%
aReaction conditions: 1) 1 (0.2 mmol), 2 (0.4 mmol), Cu(OAc)2 (0.04 mmol), (NH4)2S2O8 (0.4 mmol),
CH3CN/HCO2H (3.0 mL/1.0 mL), under N2, 50 °C, 12 h; 2) mꢀCPBA (1.0 mmol), DCM (10.0 mL), rt, 2
h. Yields are those of the isolated products.
Considering the importance of sulfonylated compounds in organic synthesis and medicinal
chemistry,17 we then turned our attention to prepare sulfonylated butenolides. After optimization of the
reaction conditions (see the Supporting Information), we were pleased to find that reaction of 2,3ꢀ
allenoic acids 1 and diaryldisulfides 2 under the standard conditions followed by the oxidation with mꢀ
CPBA (mꢀchloroperbenzoic acid) could deliver the corresponding sulfonylated butenolides 4 in high
yields (Scheme 4). Both of the electronꢀdonating and electronꢀwithdrawing groups on the aromatic ring
of 2,3ꢀallenoic acids 1 or diaryldisulfides 2 were well tolerated. Unfortunately, dialkyldisulfides were
not suitable substrates for this transformation, as a complex mixture was obtained. This procedure
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provided a convenient and efficient approach to sulfonylated butenolides without purification of the
sulfide intermediates. Notably, no sulfinylated product was isolated in this reaction.
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8
9
To further probe the applicability of this method, the tandem selenylation/cyclization was also tested.
As shown in Scheme 5, treatment of 2ꢀmethylꢀ4ꢀphenylꢀ2,3ꢀallenoic acid (1a) with dibenzyldiselenide
(5a) or diphenyldiselenide (5b) under the standard conditions provided selenylated butenolides 6a and
6b in good yields, respectively. To the best of our knowledge, these results represent the first example of
preparation of selenylated butenolides through radical processes.18
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Scheme 5. Selenylation of 2,3-Allenoic Acids
Scheme 6. Transformation of the Sulfenylated and Selenylated Butenolides
The synthetic value of this protocol was demonstrated by transformation of the sulfenylated and
selenylated butenolides. For example, deprotonation of sulfenylated butenolide 3h with LDA followed
by acetylation with Ac2O delivered sulfenylated furan 7 in 52% yield (Scheme 6a). Similarly,
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selenylated butenolide 6b was transformed to selenylated furan 8 in 77% yield by
1
2
3
deprotonation/acetylation (Scheme 6b).
4
5
6
7
8
To gain insight into the reaction mechanism, several mechanistic studies were carried out. When the
radical scavenger 2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy (TEMPO) or 2,6ꢀdiꢀtertꢀbutylꢀ4ꢀmethylphenol
(BHT) was added to the standard reaction conditions, most of the starting material (1a) was recovered
and only a trace amount of the desired product 3a was detected (Scheme 7a). These observations
demonstrated that a radical pathway was probably involved in this reaction. Furthermore, this reaction
could be conducted in air, but affording product 3a in a much lower yield along with the recovery of
some of the starting material (Scheme 7b), which was consistent with the fact that O2 may inhibit the
radical reaction. Finally, the control experiments with 2,3ꢀallenoate 9 or thiol 10 in place of 2,3ꢀallenoic
acid 1a or disulfide 2a could not yield any of the desired product 3a (Scheme 7c and 7d). These results
indicated that both 2,3ꢀallenoic acid and disulfide were crucial for this reaction.
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Scheme 7. Mechanistic Experiments
Cu(OAc)2 (0.2 eq)
(NH4)2S2O8 (2.0 eq)
TEMPO (2.0 eq)
or BHT (3.0 eq)
BnS
COOH
(a)
+
+
+
+
BnSSBn
CH3CN:HCO2H = 3:1
50 oC, under N2, 12 h
Ph
O
Ph
O
1a
2a
3a
, trace
BnS
Cu(OAc)2 (0.2 eq)
(NH4)2S2O8 (2.0 eq)
COOH
CO2Et
COOH
(b)
(c)
(d)
BnSSBn
CH3CN:HCO2H = 3:1
Ph
O
O
O
Ph
Ph
Ph
50 oC, in air, 12 h
O
1a
9
2a
3a
, 21%
BnS
Cu(OAc)2 (0.2 eq)
(NH4)2S2O8 (2.0 eq)
BnSSBn
CH3CN:HCO2H = 3:1
50 oC, under N2, 12 h
Ph
O
3a, 0
2a
BnS
Cu(OAc)2 (0.2 eq)
(NH4)2S2O8 (2.0 eq)
BnSH
CH3CN:HCO2H = 3:1
50 oC, under N2, 12 h
Ph
O
1a
10
3a, 0
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Based on the above results and literature precedents,15,19 a plausible mechanism for the reaction is
1
2
proposed in Scheme 8. First, disulfides were oxidized to the sulfenyl radical by (NH4)2S2O8. Then, the
addition of sulfenyl radical to 2,3ꢀallenoic acids 1 generated the radical intermediate A, which could be
further oxidized by Cu(II) for the formation of intermediate B. Finally, the intramolecular attack of
intermediate B furnished the cyclized products 3 (path A). Alternatively, another pathway is also
possible. The coordination of Cu(II) with 2,3ꢀallenoic acids 1 formed complex C. Subsequently, the
reaction of complex C and sulfenyl radical provided Cu(III) intermediate D, which would undergo
reductive elimination to release the desired product 3 (path B). In both pathways, the regenerated Cu(I)
species could be oxidized to Cu(II) species for the next catalytic cycle. However, the exact mechanism
of this transformation remains unclear at the present stage.
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Scheme 8. Proposed Reaction Mechanism
RS
R1
R3
RS
R1
R3
COOH
CO2
R2
R2
RSSR
A
B
(NH4)2S2O8
Cu(II)
Cu(I)
SR
path A
R3
RS
R1
R3
R1
R2
[O]
[O]
O
O
R2
O
3
HO
1
Cu(I)
Cu(II)
R3
path B
RS
R1
R2
R3
R1
R2
O
O
O
CuII
CuIII
O
C
D
SR
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Conclusion
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We have developed a copperꢀcatalyzed sulfenylation and selenylation of 2,3ꢀallenoic acids with
disulfides or diselenides, to afford a series of 4ꢀsulfenylated and 4ꢀselenylated butenolides in moderate
to excellent yields. This protocol also allows a convenient access to 4ꢀsulfonylated butenolides by
tandem sulfenylation/cyclization and subsequent oxidation. Furthermore, the sulfenylated and
selenylated butenolides could be transformed to the corresponding furan derivatives. Most of these
sulfenylated, sulfonylated, and selenylated butenolides are previous unknown and might have potential
utility in medical chemistry. Further exploration of the reaction mechanism and the application of this
method are underway in our laboratory.
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Experimental Section
General Experimental Methods. 1H NMR (TMS as the internal standard) and 19F NMR spectra (CFCl3
13
as the outside standard and low field is positive) were recorded on a 400 MHz spectrometer. C NMR
was recorded on 400 MHz spectrometer. Chemical shifts (δ) are reported in ppm, and coupling constants
(J) are in Hertz (Hz). The following abbreviations were used to explain the multiplicities: s = singlet, d
= doublet, t = triplet, q = quartet, m = multiplet. HRMS data were obtained on a GCꢀTOF mass
spectrometer. Unless otherwise noted, all reagents were obtained commercially and used without further
purification. Substrates were purchased from commercial sources or were prepared according to
literature procedures.
General procedure for sulfenylation of 2,3-allenoic acids
A 25 mL Schlenk tube equipped with a magnetic stir bar was charged with 2,3ꢀallenoic acid (0.2 mmol,
1.0 equiv), Cu(OAc)2 (7.2 mg, 0.04 mmol, 0.2 equiv), disulfides (0.4 mmol, 2.0 equiv), and (NH4)2S2O8
(91.3 mg, 0.4 mmol, 2.0 equiv). The tube was sealed with a septum, evacuated, and backfilled with
nitrogen three times. Then CH3CN (3.0 mL) and HCO2H (1.0 mL) were added by a syringe. The mixture
was stirred at 50 oC for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous
solution was added. The resulting mixture was filtered by Celite, eluted with DCM. The organic phase
was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced vacuum. The
residue was purified with silica gel column chromatography to provide the pure product.
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The Journal of Organic Chemistry
4-(Benzylthio)-3-methyl-5-phenylfuran-2(5H)-one (3a). Compound 3a was obtained as a yellow oil
1
2
3
1
(51.0 mg, 86%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.32 (dd, J = 5.0, 1.7 Hz, 3H), 7.22ꢀ7.14 (m, 5H), 7.05ꢀ7.01 (m, 2H), 5.61 (s, 1H), 3.76
(d, J = 13.1 Hz, 1H), 3.59 (d, J = 13.1 Hz, 1H), 1.85 (d, J = 1.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
ppm 172.2, 158.1, 135.5, 134.5, 130.0, 129.2, 128.9, 128.6, 128.0, 127.9, 123.8, 83.5, 35.4, 9.6; IR (thin
film) ν 1737, 1630, 1494, 1456, 1313, 1290, 1087, 988, 907 cmꢀ1; MS (ESI): m/z 297 [M+H]+; HRMS
(ESIꢀTOF): m/z [M+H]+ Calculated for C18H17O2S: 297.0944; Found: 297.0941.
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4-(Benzylthio)-3-methyl-5-p-tolylfuran-2(5H)-one (3b). Compound 3b was obtained as a yellow oil
1
(47.2 mg, 76%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.19ꢀ7.15 (m, 3H), 7.14 (d, J = 6.1 Hz, 2H), 7.10 (d, J = 5.7 Hz, 2H), 7.08ꢀ7.03 (m, 2H),
5.58 (d, J = 1.5 Hz, 1H), 3.75 (d, J = 13.1 Hz, 1H), 3.60 (d, J = 13.1 Hz, 1H), 2.27 (s, 3H), 1.84 (d, J =
1.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 171.2, 157.1, 138.9, 134.5, 130.4, 128.8, 127.8, 127.5,
126.9, 126.8, 122.4, 82.3, 34.2, 20.3, 8.5; IR (thin film) ν 1740, 1616, 1505, 1397, 1288, 1078, 821, 704
cmꢀ1; MS (ESI): m/z 311 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C19H19O2S: 311.1100;
Found: 311.1098.
4-(Benzylthio)-5-(4-methoxyphenyl)-3-methylfuran-2(5H)-one (3c). Compound 3c was obtained as a
1
yellow oil (56.3 mg, 86%), hexane/EA = 3:1 as eluent for the column chromatography. H NMR (400
MHz, CDCl3) δ ppm 7.19 (t, J = 7.3 Hz, 3H), 7.14 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 7.9 Hz, 2H), 6.85 (d,
J = 8.7 Hz, 2H), 5.59 (d, J = 1.5 Hz, 1H), 3.77 (d, J = 13.1 Hz, 1H), 3.73 (s, 3H), 3.62 (d, J = 13.1 Hz,
13
1H), 1.85 (d, J = 1.5 Hz, 3H); C NMR (100 MHz, CDCl3) δ ppm 171.1, 159.8, 157.0, 134.5, 128.3,
127.8, 127.5, 126.9, 125.3, 122.3, 113.5, 82.1, 54.3, 34.1, 8.5; IR (thin film) ν 1725, 1616, 1488, 1405,
1288, 1203, 1087, 907, 880 cmꢀ1; MS (ESI): m/z 349 [M+Na]+; HRMS (ESIꢀTOF): m/z [M+H]+
Calculated for C19H19O3S: 327.1049; Found: 327.1048.
4-(Benzylthio)-5-(4-fluorophenyl)-3-methylfuran-2(5H)-one (3d). Compound 3d was obtained as a
yellow oil (47.3 mg, 75%), hexane/EA = 5:1 as eluent for the column chromatography. 1H NMR (400
MHz, CDCl3) δ ppm 7.23ꢀ7.12 (m, 5H), 7.06ꢀ6.95 (m, 4H), 5.59 (s, 1H), 3.77 (d, J = 13.1 Hz, 1H), 3.62
19
(d, J = 13.1 Hz, 1H), 1.85 (d, J = 1.5 Hz, 3H); F NMR (377 MHz, CDCl3) δ ꢀ110.61 to ꢀ110.68 (m,
1F); 13C NMR (100 MHz, CDCl3) δ ppm 170.9, 162.4 (d, J = 250.5 Hz), 156.8, 134.3, 129.4 (d, J = 3.0
Hz), 128.8 (d, J = 9.1 Hz), 127.9, 127.5, 127.0, 123.0, 115.3, 81.6, 34.4, 8.6; IR (thin film) ν 1744, 1606,
1509, 1289, 1229, 1079, 987, 908, 839 cmꢀ1; MS (ESI): m/z 315 [M+H]+; HRMS (ESIꢀTOF): m/z
[M+H]+ Calculated for C18H16FO2S: 315.0850; Found: 315.0847.
4-(Benzylthio)-5-(4-chlorophenyl)-3-methylfuran-2(5H)-one (3e). Compound 3e was obtained as a
1
yellow oil (46.1 mg, 70%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400
MHz, CDCl3) δ ppm 7.30ꢀ7.25 (m, 2H), 7.20ꢀ7.15 (m, 3H), 7.14ꢀ7.09 (m, 2H), 7.04 (dd, J = 7.4, 1.8 Hz,
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2H), 5.57 (d, J = 1.5 Hz, 1H), 3.77 (d, J = 13.2 Hz, 1H), 3.63 (d, J = 13.2 Hz, 1H), 1.85 (d, J = 1.6 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ ppm 170.9, 156.6, 134.8, 134.3, 132.0, 128.3, 128.2, 127.9, 127.5,
127.0, 123.3, 81.6, 34.5, 8.6; IR (thin film) ν 1742, 1616, 1492, 1289, 1076, 987, 908 cmꢀ1; MS (ESI):
m/z 331 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C18H16ClO2S: 331.0554; Found:
331.0552.
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4-(Benzylthio)-5-(3-bromophenyl)-3-methylfuran-2(5H)-one (3f). Compound 3f was obtained as a
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yellow oil (63.1 mg, 84%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400
MHz, CDCl3) δ ppm 7.46ꢀ7.41 (m, 2H), 7.20ꢀ7.17 (m, 3H), 7.07ꢀ7.03 (m, 4H), 5.55 (d, J = 1.6 Hz, 1H),
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3.77 (d, J = 13.2 Hz, 1H), 3.64 (d, J = 13.2 Hz, 1H), 1.85 (d, J = 1.6 Hz, 3H); C NMR (100 MHz,
CDCl3) δ ppm 171.9, 157.6, 135.4, 133.6, 132.4, 129.5, 129.0, 128.5, 128.1, 124.4, 124.1, 82.7, 35.5,
9.7; IR (thin film) ν 1744, 1616, 1489, 1390, 1289, 1068, 988, 908 cmꢀ1; MS (ESI): m/z 375 [M+H]+;
HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C18H16BrO2S: 375.0049; Found: 375.0045.
4-(Benzylthio)-3-methyl-5-(4-(trifluoromethyl)phenyl)furan-2(5H)-one (3g). Compound 3g was
1
obtained as a yellow oil (50.8 mg, 70%), hexane/EA = 5:1 as eluent for the column chromatography. H
NMR (400 MHz, CDCl3) δ ppm 7.70 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.33ꢀ7.30 (m, 3H),
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7.19ꢀ7.14 (m, 2H), 5.74 (s, 1H), 3.91 (d, J = 13.3 Hz, 1H), 3.79 (d, J = 13.3 Hz, 1H), 2.01 (s, 3H); F
13
NMR (377 MHz, CDCl3) δ ꢀ62.77 (s, 3F); C NMR (100 MHz, CDCl3) δ ppm 171.9, 157.4, 138.5,
135.3, 131.9 (q, J = 32.8 Hz), 129.0, 128.5, 128.2, 128.1, 126.1 (q, J = 3.7 Hz), 125.1, 123.7 (q, J =
272.4 Hz), 82.6, 35.7, 9.8; IR (thin film) ν 1766, 1623, 1501, 1408, 1289, 1088, 992, 880 cmꢀ1; MS
(ESI): m/z 365 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C19H16F3O2S: 365.0818; Found:
365.0818.
4-(Benzylthio)-3-methyl-5-(naphthalen-2-yl)furan-2(5H)-one (3h). Compound 3h was obtained as a
1
yellow oil (62.5 mg, 90%), hexane/EA = 10:1 as eluent for the column chromatography. H NMR (400
MHz, CDCl3) δ ppm 8.01 (d, J = 8.3 Hz, 1H), 7.90ꢀ7.84 (m, 2H), 7.56ꢀ7.47 (m, 2H), 7.43 (d, J = 4.6 Hz,
2H), 7.18ꢀ7.12 (m, 3H), 6.92 (dd, J = 6.3, 2.7 Hz, 2H), 6.42ꢀ6.39 (m, 1H), 3.64 (d, J = 13.3 Hz, 1H),
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3.54 (d, J = 13.3 Hz, 1H), 1.94 (d, J = 1.6 Hz, 3H); C NMR (100 MHz, CDCl3) δ ppm 170.9, 157.0,
134.3, 133.0, 130.8, 129.7, 129.0, 128.0, 127.8, 127.5, 126.9, 126.2, 125.3, 124.5, 124.4, 122.8, 121.7,
78.1, 34.3, 8.7; IR (thin film) ν 1744, 1616, 1540, 1478, 1409, 1291, 1090, 976, 789 cmꢀ1; MS (ESI):
m/z 347 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C22H19O2S: 347.1100; Found:
347.1097.
4-(Benzylthio)-5-(2,5-dimethylphenyl)-3-methylfuran-2(5H)-one (3i). Compound 3i was obtained as a
1
yellow oil (37.1 mg, 57%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400
MHz, CDCl3) δ ppm 7.21ꢀ7.15 (m, 3H), 7.04ꢀ6.99 (m, 4H), 6.86 (s, 1H), 5.82 (d, J = 1.6 Hz, 1H), 3.72
(d, J = 13.2 Hz, 1H), 3.59 (d, J = 13.2 Hz, 1H), 2.26 (s, 3H), 2.22 (s, 3H), 1.88 (d, J = 1.6 Hz, 3H); 13C
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The Journal of Organic Chemistry
NMR (100 MHz, CDCl3) δ ppm 171.2, 157.1, 135.3, 134.4, 133.4, 131.0, 130.0, 129.5, 127.8, 127.4,
126.9, 126.6, 122.6, 79.4, 34.1, 20.0, 17.5, 8.6; IR (thin film) ν 1742, 1616, 1495, 1454, 1289, 1080, 980,
906 cmꢀ1; MS (ESI): m/z 325 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C20H21O2S:
325.1257; Found: 325.1256.
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4-(Benzylthio)-3,5-dimethyl-5-phenylfuran-2(5H)-one (3j). Compound 3j was obtained as a yellow oil
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(56.0 mg, 90%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
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CDCl3) δ ppm 7.29–7.27 (m, 5H), 7.17–7.15 (m, 3H), 6.98 (dd, J = 6.5, 2.8 Hz, 2H), 3.78 (d, J = 12.6
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Hz, 1H), 3.66 (d, J = 12.6 Hz, 1H), 1.84 (s, 3H), 1.72 (s, 3H); C NMR (100 MHz, CDCl3) δ ppm
172.5, 162.6, 138.3, 136.0, 128.81, 128.77, 128.74, 128.69, 127.9, 126.2, 125.6, 88.6, 37.2, 24.2, 10.3;
IR (thin film) ν 1740, 1616, 1454, 1329, 1088, 1045, 880, 698 cmꢀ1; MS (ESI): m/z 311 [M+H]+; HRMS
(ESIꢀTOF): m/z [M+H]+ Calculated for C19H19O2S: 311.1100; Found: 311.1097.
4-(Benzylthio)-3-butyl-5-phenylfuran-2(5H)-one (3k). Compound 3k was obtained as a yellow oil
1
(60.6 mg, 90%), hexane/EA = 10:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.38ꢀ7.32 (m, 3H), 7.25ꢀ7.14 (m, 5H), 7.08ꢀ7.02 (m, 2H), 5.64 (s, 1H), 3.74 (d, J = 13.1
Hz, 1H), 3.58 (d, J = 13.1 Hz, 1H), 2.39ꢀ2.22 (m, 2H), 1.55ꢀ1.42 (m, 2H), 1.37ꢀ1.23 (m, 2H), 0.86 (t, J =
7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 171.8, 158.0, 135.5, 134.6, 130.0, 129.3, 128.9, 128.6,
128.1, 128.02, 127.98, 83.2, 35.3, 29.6, 24.3, 22.7, 13.9; IR (thin film) ν 2973, 1736, 1616, 1455, 1380,
1274, 1087, 880 cmꢀ1; MS (ESI): m/z 339 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for
C21H23O2S: 339.1413; Found: 339.1411.
3-Methyl-4-(methylthio)-5-phenylfuran-2(5H)-one (3l). Compound 3l was obtained as a yellow oil
1
(26.9 mg, 61%), hexane/EA = 3:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.36ꢀ7.32 (m, 3H), 7.26ꢀ7.21 (m, 2H), 5.75 (d, J = 1.6 Hz, 1H), 2.07 (s, 3H), 1.90 (d, J =
1.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 171.2, 158.2, 133.6, 128.9, 128.2, 126.8, 121.0, 82.1,
12.6, 8.3; IR (thin film) ν 1741, 1618, 1457, 1290, 1083, 992, 906 cmꢀ1; MS (ESI): m/z 221 [M+H]+;
HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C12H13O2S: 221.0631; Found: 221.0629.
4-(Isopropylthio)-3-methyl-5-phenylfuran-2(5H)-one (3m). Compound 3m was obtained as a yellow
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oil (32.0 mg, 64%), hexane/EA = 4:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.39ꢀ7.29 (m, 3H), 7.21 (dd, J = 6.4, 3.0 Hz, 2H), 5.77ꢀ5.68 (m, 1H), 1.91 (d, J = 1.3 Hz,
13
1H), 1.29ꢀ1.24 (m, 3H), 1.18 (s, 3H), 1.02 (d, J = 6.8 Hz, 3H); C NMR (100 MHz, CDCl3) δ ppm
172.6, 158.6, 134.8, 129.8, 129.0, 127.6, 124.4, 83.9, 36.2, 24.8, 23.1, 9.8; IR (thin film) ν 2921, 1750,
1616, 1496, 1380, 1290, 1083, 987 cmꢀ1; MS (ESI): m/z 271 [M+Na]+; HRMS (ESIꢀTOF): m/z [M+H]+
Calculated for C14H17O2S: 249.0944; Found: 249.0944.
4-(Butylthio)-3-methyl-5-phenylfuran-2(5H)-one (3n). Compound 3n was obtained as a yellow oil
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(37.4 mg, 71%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
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CDCl3) δ ppm 7.37ꢀ7.27 (m, 3H), 7.21 (dd, J = 5.7, 2.3 Hz, 2H), 5.74 (s, 1H), 2.69ꢀ2.55 (m, 1H), 2.45ꢀ
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2.34 (m, 1H), 1.88 (s, 3H), 1.42ꢀ1.27 (m, 2H), 1.26ꢀ1.12 (m, 2H), 0.73 (t, J = 7.3 Hz, 3H); C NMR
(100 MHz, CDCl3) δ ppm 171.4, 158.2, 133.7, 128.8, 128.1, 126.8, 121.4, 82.4, 30.6, 29.4, 20.5, 12.3,
8.5; IR (thin film) ν 2973, 1736, 1615, 1498, 1378, 1252, 1046, 880 cmꢀ1; MS (ESI): m/z 263 [M+H]+;
HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C15H19O2S: 263.1100; Found: 263.1098.
4-(Tert-butylthio)-3-methyl-5-phenylfuran-2(5H)-one (3o). Compound 3o was obtained as a yellow oil
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(35.6 mg, 68%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.33ꢀ7.28 (m, 3H), 7.21 (dd, J = 6.8, 2.9 Hz, 2H), 6.01 (d, J = 1.5 Hz, 1H), 1.99 (d, J =
1.6 Hz, 3H), 1.25 (s, 9H); 13C NMR (100 MHz, CDCl3) δ ppm 171.2, 159.9, 133.6, 128.4, 127.8, 126.6,
124.6, 82.5, 48.8, 28.6, 8.8; IR (thin film) ν 1755, 1616, 1457, 1297, 1162, 1089, 903 cmꢀ1; MS (ESI):
m/z 263 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C15H19O2S: 263.1100; Found:
263.1098.
4-(Hexylthio)-3-methyl-5-phenylfuran-2(5H)-one (3p). Compound 3p was obtained as a yellow oil
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(46.0 mg, 79%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.36ꢀ7.30 (m, 3H), 7.24ꢀ7.20 (m, 2H), 5.73 (d, J = 1.5 Hz, 1H), 2.67ꢀ2.59 (m, 1H), 2.45ꢀ
2.36 (m, 1H), 1.89 (d, J = 1.5 Hz, 3H), 1.44ꢀ1.28 (m, 2H), 1.21ꢀ1.04 (m, 6H), 0.78 (t, J = 7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ ppm 171.3, 158.1, 133.8, 128.8, 128.1, 126.8, 121.6, 82.4, 30.0, 29.8,
28.6, 27.0, 21.4, 12.9, 8.5; IR (thin film) ν 2972, 1744, 1616, 1456, 1288, 1081, 986 cmꢀ1; MS (ESI):
m/z 291 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C17H23O2S: 291.1413; Found:
291.1413.
4-(Cyclohexylthio)-3-methyl-5-phenylfuran-2(5H)-one (3q). Compound 3q was obtained as a yellow
1
oil (34.7 mg, 60%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.34ꢀ7.30 (m, 3H), 7.23ꢀ7.18 (m, 2H), 5.73 (s, 1H), 2.92ꢀ2.82 (m, 1H), 1.89 (s, 3H), 1.83
13
(d, J = 13.0 Hz, 1H), 1.71ꢀ1.62 (m, 1H), 1.57ꢀ1.49 (m, 1H), 1.49ꢀ1.39 (m, 2H), 1.29ꢀ1.10 (m, 5H); C
NMR (100 MHz, CDCl3) δ ppm 171.6, 157.6, 133.9, 128.7, 128.0, 126.6, 122.7, 82.9, 43.0, 33.8, 32.2,
24.7, 24.1, 8.7; IR (thin film) ν 2919, 1746, 1616, 1497, 1409, 1289, 1088, 985 cmꢀ1; MS (ESI): m/z 289
[M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C17H21O2S: 289.1257; Found: 289.1261.
3-Methyl-5-phenyl-4-(phenylthio)furan-2(5H)-one (3r). Compound 3r was obtained as a yellow oil
1
(19.5mg, 33%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.34ꢀ7.23 (m, 3H), 7.09ꢀ7.02 (m, 4H), 6.88 (d, J = 7.4 Hz, 2H), 5.57 (s, 1H), 2.37 (s, 3H),
1.94 (s, 3H); 13C NMR (100 MHz, CDCl3) δ ppm 172.5, 159.6, 140.0, 134.7, 134.4, 130.1, 129.3, 128.5,
127.5, 123.8, 122.4, 83.4, 21.3, 9.5; IR (thin film) ν 2934, 2840, 1602, 1503, 1380, 1262, 1080, 998, 805
cmꢀ1; MS (ESI): m/z 297 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C18H17O2S: 297.0944;
Found: 297.0943.
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General procedure for sulfonylation of 2,3-allenoic acids
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A 25 mL Schlenk tube equipped with a magnetic stir bar was charged with 2,3ꢀallenoic acid (0.2 mmol,
1.0 equiv), Cu(OAc)2 (7.2 mg, 0.04 mmol, 0.2 equiv), disulfides (0.4 mmol, 2.0 equiv), and (NH4)2S2O8
(91.3 mg, 0.4 mmol, 2.0 equiv). The tube was sealed with a septum, evacuated, and backfilled with
nitrogen three times. Then CH3CN (3.0 mL) and HCO2H (1.0 mL) was added by a syringe. The mixture
was stirred at 50 oC for 12 h. After the reaction was complete, a saturated ammonium chloride aqueous
solution was added. The resulting mixture was filtered by Celite, eluted with DCM (10.0 mL). Then, mꢀ
CPBA (172.6 mg, 1.0 mmol, 5 equiv) was added and the mixture was stirred at room temperature for 2
hours. After that, the organic phase was washed with brine, dried over Na2SO4, filtered, and
concentrated under reduced vacuum. The residue was purified with silica gel column chromatography to
provide the pure product.
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3-Methyl-5-phenyl-4-tosylfuran-2(5H)-one (4a). Compound 4a was obtained as a white solid (57.8 mg,
88%), hexane/EA = 3:1 as eluent for the column chromatography. MP: 112ꢀ114 oC. 1H NMR (400 MHz,
CDCl3) δ ppm 7.26 (d, J = 7.5 Hz, 1H), 7.15 (t, J = 7.6 Hz, 2H), 7.07 (d, J = 8.3 Hz, 2H), 7.01ꢀ6.95 (m,
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4H), 5.98 (d, J = 2.0 Hz, 1H), 2.30 (s, 3H), 2.29 (s, 3H); C NMR (100 MHz, CDCl3) δ ppm 170.0,
155.8, 144.6, 135.2, 134.7, 131.3, 128.7, 127.7, 126.9, 126.8, 81.5, 20.6, 9.3; IR (thin film) ν 2919, 1772,
1659, 1470, 1378, 1153, 700 cmꢀ1; MS (ESI): m/z 329 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+
Calculated for C18H17O4S: 329.0842; Found: 329.0846. These data matched with the reported results.20
4-((4-Chlorophenyl)sulfonyl)-3-methyl-5-phenylfuran-2(5H)-one (4b). Compound 4b was obtained as
a white solid (48.6 mg, 70%), hexane/EA = 3:1 as eluent for the column chromatography. MP: 140ꢀ142
oC. 1H NMR (400 MHz, CDCl3) δ ppm 7.28 (t, J = 7.4 Hz, 1H), 7.20ꢀ7.06 (m, 6H), 6.94 (d, J = 7.5 Hz,
13
2H), 5.98 (d, J = 2.0 Hz, 1H), 2.31 (d, J = 2.0 Hz, 3H); C NMR (100 MHz, CDCl3) δ ppm 169.7,
155.0, 140.2, 136.2, 136.1, 131.1, 128.9, 128.4, 128.1, 127.8, 126.9, 81.3, 9.4; IR (thin film) ν2920,
1773, 1652, 1598, 1466, 1330, 1154, 1000, 702 cmꢀ1; MS (ESI): m/z 349 [M+H]+; HRMS (ESIꢀTOF):
m/z [M+H]+ Calculated for C17H14ClO4S: 349.0296; Found: 349.0295.
3-Methyl-5-phenyl-4-(phenylsulfonyl)furan-2(5H)-one (4c). Compound 4c was obtained as a white
o
1
solid (49.7 mg, 79%), hexane/EA = 3:1 as eluent for the column chromatography. MP: 115ꢀ117 C. H
NMR (400 MHz, CDCl3) δ ppm 7.44 (dt, J = 8.5, 3.9 Hz, 1H), 7.20 (d, J = 5.2 Hz, 5H), 7.13 (t, J = 7.6
13
Hz, 2H), 6.95 (d, J = 7.7 Hz, 2H), 6.00 (d, J = 2.0 Hz, 1H), 2.33 (d, J = 2.0 Hz, 3H); C NMR (100
MHz, CDCl3) δ ppm 169.9, 155.4, 137.7, 135.8, 133.2, 131.1, 128.8, 128.1, 127.7, 126.9, 126.7, 81.5,
9.4; IR (thin film) ν 1754, 1552, 1473, 1264, 896, 731 cmꢀ1; MS (ESI): m/z 337 [M+Na]+; HRMS (ESIꢀ
TOF): m/z [M+H]+ Calculated for C17H15O4S: 315.0686; Found: 315.0685.
3-Methyl-4-(phenylsulfonyl)-5-(p-tolyl)furan-2(5H)-one (4d). Compound 4d was obtained as a white
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1
solid (54.2 mg, 82%), hexane/EA = 3:1 as eluent for the column chromatography. MP: 118ꢀ120 C. H
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NMR (400 MHz, CDCl3) δ ppm 7.51 (t, J = 6.9 Hz, 1H), 7.32ꢀ7.23 (m, 4H), 6.99 (d, J = 7.9 Hz, 2H),
6.88 (d, J = 8.0 Hz, 2H), 6.02 (d, J = 2.0 Hz, 1H), 2.39 (d, J = 2.1 Hz, 3H), 2.32 (s, 3H); 13C NMR (100
MHz, CDCl3) δ ppm 171.0, 156.5, 140.0, 138.8, 136.6, 134.1, 129.4, 129.02, 128.99, 127.8, 82.4, 77.4,
21.3, 10.4; IR (thin film) ν 2919, 1772, 1646, 1575, 1448, 1329, 1155, 1087, 998 cmꢀ1; MS (ESI): m/z
351 [M+Na]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C18H17O4S: 329.0842; Found: 329.0841.
5-(4-Chlorophenyl)-3-methyl-4-(phenylsulfonyl)furan-2(5H)-one (4e). Compound 4e was obtained as
a white solid (52.3 mg, 75%), hexane/EA = 3:1 as eluent for the column chromatography. MP: 139ꢀ141
oC. 1H NMR (400 MHz, CDCl3) δ ppm 7.52ꢀ7.48 (m, 1H), 7.26 (d, J = 4.1 Hz, 4H), 7.10 (d, J = 8.4 Hz,
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2H), 6.88 (d, J = 8.4 Hz, 2H), 5.96 (d, J = 2.0 Hz, 1H), 2.33 (d, J = 2.1 Hz, 3H); C NMR (100 MHz,
CDCl3) δ ppm 169.6, 155.2, 137.7, 136.0, 135.0, 133.4, 129.7, 128.21, 128.16, 128.0, 126.6, 80.5, 9.4;
IR (thin film) ν 2919, 1773, 1647, 1494, 1378, 1155, 1088, 998 cmꢀ1; MS (ESI): m/z 349 [M+H]+;
HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C17H14ClO4S: 349.0296; Found: 349.0298.
5-(4-Bromophenyl)-3-methyl-4-(phenylsulfonyl)furan-2(5H)-one (4f). Compound 4f was obtained as a
white solid (60.1 mg, 77%), hexane/EA = 3:1 as eluent for the column chromatography. MP: 142ꢀ144
oC. 1H NMR (400 MHz, CDCl3) δ ppm 7.51ꢀ7.46 (m, 1H), 7.35 (d, J = 7.5 Hz, 1H), 7.26 (s, 4H), 7.08ꢀ
6.99 (m, 2H), 6.89 (s, 1H), 5.94ꢀ5.91 (m, 1H), 2.35 (d, J = 1.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
ppm 169.5, 154.8, 137.5, 136.2, 133.6, 133.4, 132.0, 129.4, 129.3, 128.2, 126.6, 125.9, 121.8, 80.4, 9.5;
IR (thin film) ν 2973, 1788, 1656, 1499, 1274, 1088, 880 cmꢀ1; MS (ESI): m/z 393 [M+H]+; HRMS
(ESIꢀTOF): m/z [M+H]+ Calculated for C17H14BrO4S: 392.9791; Found: 392.9796.
3-Methyl-4-(phenylsulfonyl)-5-(4-(trifluoromethyl)phenyl)furan-2(5H)-one (4g). Compound 4g was
obtained as a white solid (50.6 mg, 66%), hexane/EA = 3:1 as eluent for the column chromatography.
MP: 125ꢀ127 oC. 1H NMR (400 MHz, CDCl3) δ ppm 7.48ꢀ7.42 (m, 1H), 7.38 (d, J = 8.2 Hz, 2H), 7.20
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(d, J = 5.0 Hz, 4H), 7.09 (d, J = 8.1 Hz, 2H), 6.04 (d, J = 2.0 Hz, 1H), 2.36 (d, J = 2.0 Hz, 3H); F
13
NMR (377 MHz, CDCl3) δ ꢀ62.89 (s, 3F); C NMR (100 MHz, CDCl3) δ ppm 169.5, 155.0, 137.6,
136.3, 135.3, 133.5, 131.0 (q, J = 32.8 Hz), 128.2, 127.3, 126.5, 124.7 (q, J = 3.8 Hz), 122.5 (q, J =
273.7 Hz), 80.4, 9.5; IR (thin film) ν 2920, 1776, 1647, 1448, 1378, 1154, 1088, 1000, 872 cmꢀ1; MS
(ESI): m/z 400 [M+NH4]+; HRMS (ESIꢀTOF): m/z [M+NH4]+ Calculated for C18H17F3NO4S: 400.0825;
Found: 400.0822.
3-Butyl-5-phenyl-4-(phenylsulfonyl)furan-2(5H)-one (4h). Compound 4h was obtained as a white
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1
solid (51.9 mg, 73%), hexane/EA = 3:1 as eluent for the column chromatography. MP: 118ꢀ120 C. H
NMR (400 MHz, CDCl3) δ ppm 7.45ꢀ7.41 (m, 1H), 7.27ꢀ7.18 (m, 5H), 7.14 (t, J = 7.6 Hz, 2H), 6.94 (d,
J = 7.2 Hz, 2H), 5.97 (s, 1H), 2.79ꢀ2.66 (m, 2H), 1.66ꢀ1.45 (m, 2H), 1.46ꢀ1.34 (m, 2H), 0.92 (t, J = 7.2
13
Hz, 3H); C NMR (100 MHz, CDCl3) δ ppm 169.6, 155.0, 140.0, 137.8, 133.1, 131.3, 128.8, 128.0,
127.8, 126.9, 126.8, 81.3, 29.3, 23.8, 22.0, 12.8; IR (thin film) ν 2920, 2841, 1800, 1652, 1522, 1380,
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1132, 1012, 752 cmꢀ1; MS (ESI): m/z 357 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for
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C20H21O4S: 357.1155; Found: 357.1156.
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General procedure for selenylation of 2,3-allenoic acids
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A 25 mL Schlenk tube equipped with a magnetic stir bar was charged with 2,3ꢀallenoic acid (0.2 mmol,
1.0 equiv), Cu(OAc)2 (7.2 mg, 0.04 mmol, 0.2 equiv), diselenides (0.4 mmol, 2.0 equiv), and
(NH4)2S2O8 (91.3 mg, 0.4 mmol, 2.0 equiv). The tube was sealed with a septum, evacuated, and
backfilled with nitrogen three times. Then CH3CN (3.0 mL) and HCO2H (1.0 mL) was added by a
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syringe. The mixture was stirred at 50 C for 12 h. After the reaction was complete, a saturated
ammonium chloride aqueous solution was added. The resulting mixture was filtered by Celite, eluted
with DCM. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated
under reduced vacuum. The residue was purified with silica gel column chromatography to provide the
pure product.
4-(Benzylselanyl)-3-methyl-5-phenylfuran-2(5H)-one (6a). Compound 6a was obtained as a yellow oil
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(43.5 mg, 63%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
CDCl3) δ ppm 7.36ꢀ7.32 (m, 3H), 7.24ꢀ7.19 (m, 3H), 7.18ꢀ7.16 (m, 2H), 7.04ꢀ7.01 (m, 2H), 5.64 (d, J =
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1.6 Hz, 1H), 3.78 (d, J = 11.3 Hz, 1H), 3.59 (d, J = 11.3 Hz, 1H), 1.85 (d, J = 1.7 Hz, 3H); C NMR
(100 MHz, CDCl3) δ ppm 172.0, 154.6, 136.4, 134.5, 129.8, 129.1, 128.9, 128.8, 128.7, 127.80, 127.75,
85.2, 29.7, 10.8; IR (thin film) ν 2920, 1798, 1494, 1281, 1083, 1000, 763 cmꢀ1; MS (ESI): m/z 367
[M+Na]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C18H17O2Se: 345.0390; Found: 345.0388.
3-Methyl-5-phenyl-4-(phenylselanyl)furan-2(5H)-one (6b). Compound 6b was obtained as a yellow oil
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(54.1 mg, 82%), hexane/EA = 5:1 as eluent for the column chromatography. H NMR (400 MHz,
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CDCl3) δ ppm 7.30ꢀ7.07 (m, 8H), 6.78 (d, J = 7.4 Hz, 2H), 5.47 (s, 1H), 1.84 (d, J = 1.3 Hz, 3H); C
NMR (100 MHz, CDCl3) δ ppm 172.0, 156.5, 136.0, 134.4, 129.5, 129.4, 129.3, 128.6, 127.6, 126.8,
123.9, 84.8, 10.6; IR (thin film) ν 1742, 1499, 1379, 1275, 1088, 880 cmꢀ1; MS (ESI): m/z 331 [M+H]+;
HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C17H15O2Se: 331.0229; Found: 331.0232. These data
matched with the reported results.18c
Transformation of the sulfenylated and selenylated butenolides
4-(Benzylthio)-3-methyl-5-(naphthalen-2-yl)furan-2-yl acetate (7). A solution of LDA (2M in THF,
o
0.15 mL) was slowly added a solution of 3h (69.3 mg, 0.2 mmol) in dry THF (3.0 mL) at ꢀ78 C. After
o
the reaction mixture was stirred for 0.5 h at ꢀ78 C, Ac2O (40.9 mg, 0.4 mmol) was added slowly. The
o
mixture was stirred at ꢀ78 C for 1 h. Then, saturated ammonium chloride aqueous solution was added.
Then resulting mixture was eluted with ethyl acetate. The organic phase was washed with brine, dried
over Na2SO4, filtered, and concentrated under reduced vacuum. The residue was purified with silica gel
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column chromatography (hexane/EA = 20:1) to give product 7 as a yellow oil (40.4 mg, 52% yield). H
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NMR (400 MHz, CDCl3) δ ppm 7.78 (t, J = 7.7 Hz, 3H), 7.37ꢀ7.42 (m, 2H), 7.32 (d, J = 7.9 Hz, 1H),
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7.25 (s, 1H), 7.01 (s, 3H), 6.93ꢀ6.86 (m, 2H), 3.54 (s, 2H), 2.24 (s, 3H), 1.76 (s, 3H); C NMR (100
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7
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MHz, CDCl3) δ ppm 166.8, 148.9, 145.4, 136.5, 132.6, 130.8, 128.4, 128.1, 127.8, 127.2, 127.1, 125.9,
125.6, 125.4, 125.0, 124.8, 123.8, 114.5, 106.3, 39.0, 19.3, 6.3; IR (thin film) ν 2923, 2852, 1790, 1650,
1494, 1337, 1260, 1170, 1059, 877 cmꢀ1; MS (ESI): m/z 389 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+
Calculated for C24H21O3S: 389.1206; Found: 389.1208.
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3-Methyl-5-phenyl-4-(phenylselanyl)furan-2-yl acetate (8). A solution of LDA (2M in THF, 0.15 mL)
o
was slowly added a solution of 6a (68.7 mg, 0.2 mmol) in dry THF (3.0 mL) at ꢀ78 C. After the
o
reaction mixture was stirred for 0.5 h at ꢀ78 C, Ac2O (40.9 mg, 0.4 mmol) was added slowly. The
o
mixture was stirred at ꢀ78 C for 1 h. Then, saturated ammonium chloride aqueous solution was added.
Then resulting mixture was eluted with ethyl acetate. The organic phase was washed with brine, dried
over Na2SO4, filtered, and concentrated under reduced vacuum. The residue was purified with silica gel
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column chromatography (hexane/EA = 20:1) to give product 8 as a yellow oil (59.3 mg, 77% yield). H
NMR (400 MHz, CDCl3) δ ppm 7.85 (d, J = 7.4 Hz, 2H), 7.25 (t, J = 7.6 Hz, 2H), 7.18 (d, J = 8.2 Hz,
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3H), 7.10 (t, J = 7.3 Hz, 2H), 7.05 (d, J = 7.1 Hz, 1H), 2.23 (s, 3H), 1.72 (s, 3H); C NMR (100 MHz,
CDCl3) δ ppm 166.6, 148.5, 145.5, 130.8, 129.0, 128.3, 127.5, 127.2, 127.0, 125.4, 125.0, 107.7, 105.5,
19.2, 7.3; IR (thin film) ν2961, 2856, 1791, 1646, 1578, 1477, 1355, 1261, 1166, 1009, 872 cmꢀ1; MS
(ESI): m/z 373 [M+H]+; HRMS (ESIꢀTOF): m/z [M+H]+ Calculated for C19H17O3Se: 373.0337; Found:
373.0373.
Supporting Information Available: Optimization of reaction conditions for sulfonylation of 2,3ꢀ
1
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allenoic acid 1a, as well as copies of H and C NMR spectra. These material are available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment
This work was supported by National Natural Science Foundation of China (21332010, 21421002,
21502215), the Strategic Priority Research Program of the Chinese Academy of Sciences
(XDB20000000), and Youth Innovation Promotion Association CAS (2016234).
References
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Nishigaya, K.; Uchikoshi, H.; Chen, I.ꢀS. Cochinolide, a New γꢀAlkylidene Bicyclic Butenolide
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Shults, E. E.; Velder, J.; Schmalz, H.ꢀG.; Chernov, S. V.; Rubalava, T. V.; Gatilov, Y. V.; Henze, G.;
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(2) For selected examples, see: (a) Monovich, L. G.; Le Huérou, Y.; Rönn, M.; Molander, G. A. Total
Synthesis of (−)ꢀSteganone Utilizing a Samarium(II) Iodide Promoted 8ꢀEndo Ketyl−Olefin
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