HOTf-Catalyzed, Solvent-Free Oxyarylation of Ynol Ethers and Thioethers

Article abstract of DOI:10.1021/acs.joc.6b00535

A novel HOTf-catalyzed oxyarylation of ynol ethers and thioethers has been realized with aryl sulfoxides as the oxyarylating reagents, providing α-arylated esters or thioesters in good to excellent yields. Notably, all atoms of the starting materials were incorporated in the product (100% atom economy) and the reaction proceeded under very mild conditions. It was found that the reaction can be ran under air and that the best yields are obtained under solvent-free conditions.

Full text of DOI:10.1021/acs.joc.6b00535

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Note
HOTf-Catalyzed, Solvent-free Oxyarylation of Ynol Ethers and Thioethers
Liang Hu, Qingwen Gui, Xiang Chen, Ze Tan, and Gangguo Zhu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00535 • Publication Date (Web): 10 May 2016
Downloaded from http://pubs.acs.org on May 11, 2016
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HOTf-Catalyzed, Solvent-free Oxyarylation of Ynol Ethers and Thioethers
Liang Hu,† Qingwen Gui,† Xiang Chen, † Ze Tan†,* and Gangguo Zhu§,*
†State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical
Engineering, Hunan University, Changsha 410082, P. R. China
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§Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China
ztanze@gmail.com gangguo@zjnu.cn
O
O
R1
YR2
HOTf (10 mol %)
S
R1
YR2
R4
+
R3
S
R4
solvent-free
metal-free
R3
100 % atom economy
Y = O, S
31 examples
62-96 % yield
A novel HOTf-catalyzed oxyarylation of ynol ethers and thioethers has been realized with aryl sulfoxides
as the oxyarylating reagents, providing ɑ-arylated esters or thioesters in good to excellent yields. Notably,
all atoms of the starting materials were incorporated in the product (100 % atom economy) and the reaction
proceeds under very mild conditions. It was found that the reaction can be run under air and best yields are
obtained under solvent-free condition.
ɑ-Arylated carbonyl compounds are common structural motifs found in a number of natural
products and bioactive molecules.1 As such, the development of new methods for their synthesis is of
great importance in organic chemistry.2-14 Traditionally ɑ-arylated carbonyl compounds are
synthesized either through transition metal catalyzed couplings between a carbonyl compound2,7e.10a,12e
and an aryl electrophile such as the notable Buchwald-Hartwig arylation reaction3 or through the
reaction of pregenerated enolate anion with electrophilic aromatic derivatives of Bi(V),4 Pb(IV),5
I(III)6 and benzyne.7 Alternatively, ɑ-arylated carbonyl compounds can be efficiently synthesized from
alkynes via Claisen rearrangement.8 For example, Toste reported that benzothiepinones could be
synthesized via intramolecular rearrangement reaction between an aryl sulfoxide and a tethered alkyne
using IMesAuCl as the catalyst.9 Zhang also independently reported a similar transformation using
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dichloro(pyridine-2-carboxylato)gold(III) as the catalyst.10 Later on gold catalyzed intermolecular
versions of this reaction were developed by the groups of Asensio and Ujaque, and Davies and
Grainger (Scheme 1, Eq. 1).11 Even though these Au-catalyzed methods do allow the rapid
construction of ɑ-arylated carbonyl compounds from simple starting materials, the use of an expensive
Au catalyst can limit their practical applications. Undoubtedly, the exploration of a metal-free method
is highly desirable.8d-e,12-14 In this context, Maulide has demonstrated that they were able to synthesize
ɑ-arylated carbonyl compounds by coupling the corresponding amide or ketoester with arylsulfoxides
using Tf2O as a promoter.13 It is proposed that these reactions go through a [3,3]-sigmatropic
rearrangement process. Even more impressively, they were able to couple ynamides with aryl
sulfoxides as well under the catalysis of HOTf (trifluoromethanesulfonic acid) (Scheme 1, Eq. 2).14
Through the generation of a keteniminium intermediate followed by its coupling with sulfoxide and
subsequent [3,3]-sigmatropic rearrangement, a variety of ɑ-arylated oxazolidinones were obtained in
good yields. As part of our continuing interest on ynol ethers,15,16 we wondered whether ynol ethers,
the structures of which are analogous to ynamides, can participate in the reaction or not. Herein we
describe that not only ynol ethers and thioethers can react efficiently with aryl sulfoxides to produce
various ɑ-arylated esters using HOTf as the catalyst, the reaction can also be run under solvent-free
condition (Scheme 1, Eq. 3).17,18
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Scheme 1. Approaches to ɑ-arylated carbonyl compounds from alkyne derivatives
Previous work
O
O
R1
Ph3PAuCl (5 mol %)
CH2Cl2
S
R1
H
+
Eq. 1
S
R2
R2
O
O
O
R
O
O
S
HOTf (10 mol %)
CH2Cl2
N
O
O
Eq. 2
Eq. 3
+
N
PhS
Ph
Ph
R
This work
R1
R1
O
S
HOTf (10 mol %)
Solvent-free
YR2
YR2
R4
+
S
R3
R4
R3
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Table 1. Screening of the Reaction Conditions for HOTf-catalyzed, solvent-free oxyarylation of
5
6
ynol ethers of 1aa
O
7
8
9
n-Bu
3-tol
O
O
acid
+
n-Bu
O 3-tol
S
o
S
solvent, 70 C, 6 h
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12
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Ph Ph
Ph
1a
2a (equiv)
2a
acid (equiv)
3aa
entry
solvent
yield (%)b
1
2
3
4
5
6
7
8
1.0
1.0
1.0
1.0
1.0
2.0
2.0
2.0
2.0
2.0
1.5
2.0
2.0
2.0
HOTf (0.1)
HOTf (0.1)
HOTf (0.1)
HOTf (0.1)
HOTf (0.1)
HOTf (0.1)
HOTf (1.0)
HOTf (1.0)
HOTf (0.2)
HOTf (0.1)
HOTf (0.1)
TFA (0.1)
CH2Cl2
DCE
MeCN
toluene
13
5
12
trace
trace
27(32)c
42
50
72
dioxane
CH2Cl2
CH2Cl2
no solvent
no solvent
no solvent
no solvent
no solvent
no solvent
no solvent
9
10
11
12
13
14
85(84)d
77
45e
TsOH (0.1)
AcOH (0.1)
14
6
aReaction conditions: 1a (0.25 mmol), 2a (m equiv), acid (n equiv), 70 C, 6 h. Isolated yield. The
o
b
c
o
d
e
reaction was run at 100 C for 6 h. The reaction was run under an air atmosphere. TFA =
trifluoroacetic acid.
Initially, ynol ether 1a, which was easily prepared by Evano’s method,19 was chosen for evaluating
the reaction parameters. As a result, treating 1a with 1.0 equiv of diphenyl sulfoxide (2a), 10 mol % of
o
HOTf in CH2Cl2 at 70 C for 6 h generated ɑ-arylated ester 3aa in 13% yield (Table 1, entry 1).
Encouraged by this result, we further investigated other conditions for this reaction. Replacing CH2Cl2
with dichloroethane or MeCN afforded 3aa in lower yields whereas toluene and dioxane failed
completely (entries 2-5). Increasing the amount of 2a to 2.0 equiv or HOTf to 1.0 equiv appeared to be
beneficial, providing 3aa in 27% and 42% yields, respectively (entries 6-7). Gratifyingly, a better
yield of 50% was obtained in the absence of solvent with 1 equiv of HOTf (entry 8). On the other
hand, running the reaction under solvent free condition while decreasing the amount of HOTf back to
10 mol % turned out to be the best reaction condition, which delivered 3aa in 85% yield (entries 9 and
10). Subsequent study of other acids proved HOTf to be the optimal one while acids such as TFA
(TFA=trifluoroacetic acid), TsOH, AcOH all performed less efficiently (entries 12-14). Notably, the
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reaction could be performed under an air atmosphere without loss of the yield. Therefore, further
substrate screening was carried out using 10 mol % of HOTf and 2.0 equiv of 2a in the absence of
solvent at 70 oC under an air atmosphere for 6 h.
9
With the optimized condition in hand, we next set out to explore the scope and limitation of our
reaction and the results are summarized in Table 2. From the table, we can see that the reaction was
suitable for a wide range of aryl sulfoxides, which generally afforded the ɑ-arylated ester 3aa-3ak in
good to excellent yields under very mild conditions (Table 2, entries 1-11). Functional groups such
methyl, methoxy, chloro, aldehyde, nitro groups were well tolerated on the phenyl ring of aryl
sulfoxides (Table 2, entries 2-9). Moreover, alkyl aryl sulfoxides 2e-2j also proved to be competent
reaction partners for this transformation, leading to the generation of 3ae-3aj in excellent yields
ranging from 72-92% (Table 2, entries 5-10). Notably, an alkyl pyridine sulfoxide can also participate
in the ɑ-arylation well, affording the desired product 3ak in 81% yield (Table 2, entry 11).
Unfortunately, aryl sulfoxide 2l bearing an amino group on the phenyl ring failed to participate in the
reaction (Table 2, entry 12). This is to be expected since the unprotected amine group can neutralize
HOTf, thus shutting down the desired reaction. In addition, an α,β-unsaturated aryl sulfoxide 2m was
also found not be compatible with our reaction (Table 2, entry 13). On the other hand, as shown in
Table 2, various ynol ethers were successfully applied to the current reaction. Specifically, the R2
group of 1 had little impact on this reaction, as shown by the production of 3ba and 3ca (Table 2,
entries 14 and 15). Pleasingly, terminal alkynyl ether 1d and 1e also underwent the reaction smoothly,
giving rise to 3da and 3ea in satisfactory yield (Table 2, entries 16 and 17). We are also pleased to see
that substrates 1f-1h, possessing both C-C triple and double bonds, reacted uneventfully to form
3fa-3ha in high yields (Table 2, entries 18-20). Besides alkyl ynol ethers, aryl alkynyl ethers also
proved to be viable substrates, affording the corresponding ɑ-arylated products in good yields (Table 2,
entries 21-23). Additionally, good yields were obtained with sterically more demanding substrates
such as 1m and 1n, showing that the reaction tolerates a tertiary center at the propargylic position
(Table 2, entries 25 and 26). Remarkably, the commercially available ethyl ethynyl was also an
effective substrate, giving 3oa in 83% yield after the reaction was run at room temperature for 6 h
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(Table 2, entry 27).
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Table 2. Scope of HOTf-catalyzed, solvent-free oxyarylation of ynol ethersa
O
7
8
9
O
R1
OR2
HOTf (10 mol %)
S
R1
OR2
R4
+
solvent-free, 70 oC, 6 h
S
R3
R4
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R3
1
2
3
entry
R1/R2
R3/R4
yield (%)b
n-Bu/3-tol (1a)
Ph/Ph (2a)
84 (3aa)
89 (3ab)
71 (3ac)
67 (3ad)c
79 (3ae)
77 (3af)
83 (3ag)
70 (3ah)
75 (3ai)
92 (3aj)
81 (3ak)
trace
1
1a
4-MeC6H4/4-MeC6H4(2b)
2
1a
4-ClC6H4/4-ClC6H4 (2c)
3
1a
4-NO2C6H4/4-NO2C6H4(2d)
4
1a
Ph/Me (2e)
5
1a
4-MeC6H4/Me (2f)
6
1a
4-MeOC6H4/Me (2g)
7
1a
4-ClC6H4/Me (2h)
8
1a
4-HCOC6H4/Me (2i)
9
1a
Ph/i-Pr (2j)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
1a
Py/Me (2k)
1a
4-NH2C6H4/Me (2l)
1a
Ph/vinyl (2m)
trace
n-Bu/Ph (1b)
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
80 (3ba)
68 (3ca)
81 (3da)
84 (3ea)
81 (3fa)
83 (3ga)
73 (3ha)
78 (3ia)
66 (3ja)
68 (3ka)
64 (3la)d
65 (3ma)
60 (3na)
n-Bu/4-ClC6H4 (1c)
H/Ph (1d)
H/3-tol (1e)
allyl/Ph (1f)
allyl/3-tol (1g)
allyl/2-naphthyl (1h)
Ph/3-tol (1i)
Ph/Et (1j)
4-CF3C6H4/Et (1k)
BnCH2/3-tol (1l)
Cy/3-tol (1m)
Cy/4-ClC6H4 (1n)
H/Et (1o)
83 (3oa)e
aReaction conditions: 1 (0.25 mmol), 2 (2 equiv), HOTf (0.1 equiv), under air, 70 C, 6 h. Isolated
o
b
c
d
e
yield. CH2Cl2 (0.2 ml) was added to the standard conditions. Run at 80 oC for 10 h. Run at room
temperature for 6 h.
Subsequently, we explored the acid-promoted oxyarylation reaction of thioethers (Table 3). As a
result, we found that the oxyarylation process exhibited good compatibility with a wide variety of
substrates under the optimal reaction conditions consisted of using 2.0 equiv of diphenyl sulfoxide and
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10 mol % HOTf at 70 C for 1 h in solvent-free condition. Both aryl thioethers and alkyl thioethers
were successfully converted into the desired products in excellent yields (Table 3, entries 1-4).
Furthermore, substrates 4e-4f with longer alkyl chains produced 5e-5f in >95% yields (Table 3, entries
5 and 6), suggesting that the oxyarylation of alkynylether is a highly regioselective process.
4
5
6
7
8
9
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Table 3. Scope of HOTf-catalyzed, solvent-free oxyarylation of thioethersa
O
R5
O
HOTf (10 mol %)
SR6
R5
SR6
+
S
S
Ph Ph solvent-free, 70 oC, 1 h
Ph
4
2a
5
entry
R5/R6
yield (%)b
Ph/Ph (4a)
Ph/Et (4b)
n-Bu/Ph (4c)
n-Bu/Me (4d)
n-C6H13/Et (4e)
n-C8H17/Et (4f)
84 (5aa)
77 (5ba)
92 (5ca)
91 (5da)
95 (5ea)
96 (5fa)
1
2
3
4
5
6
aReaction conditions: 1a (0.25 mmol), 2a (2 equiv), HOTf (0.1 equiv), under air, 70 C, 1 h. Isolated
o
b
yield.
In order to gain some information on the reaction mechanism, some control experiments were
conducted (scheme 2). When 1a was reacted with a mixture of equal-molar amount of electron-rich
(di-p-tolylsulfoxide 2b) and electron-poor (di-(p-chlorophenyl)-sulfoxide 2c) sulfoxides, we found
that a mixture of product 3ab and 3ac was obtained and the ratio of 3ab:3ac is 89:11 (Eq. 4). On the
other hand, when a unsymmetrical sulfoxide like 2k was subjected to the reaction with 1a, the reaction
afforded two regioisomers 3ak and 3ak’ in a 75:25 ratio favoring 3ak (Eq. 5). Form both cases, we
can see that the rearrangement on the more electron rich arenes is preferred and this is consistent with
the proposed mechanism (see Scheme 4 below). According to the proposed mechanism, the cationic
intermediate B is formed after rearrangement and it can be stabilized by electron donating substituents
on the phenyl ring. This high preference for transferring the most electron-rich aromatics is a
remarkable feature of this sulfoxide-mediated arylation reaction.
The synthetic utility of this reaction was then investigated. By treating 5fa with triethylsilane in the
presence of 5% Pd/C in acetone at room temperature for 10h, aldehyde 6 was generated in 79% yield
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through the Fukuyama reduction (Scheme 3).20 Furthermore, ketone 7 could be obtained in 75% yield
via Pd-catalyzed thiol ester_boronic acid cross-coupling (Scheme 3).21 As such, we have developed an
operationally simple and highly efficient method for the synthesis of multifunctional aldehydes and
ketones, an important class of building blocks in medicinal and biochemistry.
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Scheme 2. Control experiments with 2ba, 2ca, and 2kb
O
n-Bu
3-tol
O
O
S
S
3ab
2b (1.0 equiv)
HOTf (10 mol %)
solvent-free, 70 oC
Eq. 4
3-tol
n-Bu
O
3-tol
+
+
O
S
O
n-Bu
1a
O
S
Cl
Cl
2c (1.0 equiv)
Cl
Cl
3ac
3ab/3ac
= 89:11
O
n-Bu
3-tol
O
S
O
S
Cl
3ak
HOTf (10 mol %)
n-Bu
O
3-tol
+
+
solvent-free, 70 oC
Eq. 5
3-tol
O
Cl
n-Bu
1a
2k
(2.0 equiv)
O
S
Cl
3ak'
3ak/3ak' = 75:25
aReaction conditions: 1a (0.25 mmol), 2b (1 equiv), 2c (1 equiv), HOTf (0.1 equiv), under air, 70 oC,
6 h. b2 equiv of 2k was used instead of 2b and 2c.
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Scheme 3. Synthesis of multifunctional aldehyde and ketone from thioester
5
6
7
8
O
C8H17
S
Pd/C (5%)
Et3SiH (3 equiv)
H
O
acetone, rt
9
C8H17
S
SEt
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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6
, 79%
O
PhB(OH)2 (1.1 equiv)
Pd2dba3 (1%), TFP (3%)
CuTc (1.5 equiv)
C8H17
S
Ph
5fa
acetone, 50 oC
7
, 75%
Scheme 4. Possible reaction mechanism
O
OTf-
OTf-
OTf-
YR2
R1
O
R2
Y
YR2
Eq. 6
O
S
2'
R1
3'
R1
1'
1
R1
YR2
HOTf
+
Ph
YR2
S
R3S
O
R3
3S
R1
2
R3
R3
O
S
Ph
R3
Y = O, S
A
B
In summary, we have developed a HOTf-catalyzed, solvent-free oxyarylation of alkynyl ethers and
thioethers for the synthesis of ɑ-arylated esters. The reaction proceeds under very mild reaction
conditions and produces a wide range of ɑ-arylated esters in high yields with excellent functional
group tolerance. It represents a highly atom-economical and efficient method for the synthesis of
ɑ-arylated carbonyl compounds.
EXPERIMENTAL SECTION
General. Unless otherwise noted, materials obtained from commercial suppliers were used directly
without further purification. Dioxane, toluene, and THF were distilled from sodium prior to use.
Column chromatography was carried out using silica gel (300−400 mesh) with petroleum
ethers/EtOAc as the eluent. H and 13C NMR spectra were measured on a 600 or 400 MHz NMR
1
spectrometer using CDCl3 as the solvent. The chemical shifts are given in δ relative to TMS, and the
coupling constants are given in Hertz. The high-resolution mass spectra (HRMS) analyses were
conducted using a TOF MS instrument with an ESI source. Melting points were measured by a
melting point instrument and were uncorrected.
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General procedure for synthesis of vinyl dibromides from aldehydes (First step)22:
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Under an atmosphere of argon, a solution of triphenylphosphine (4 eq.) and tetrabromomethane (2 eq.)
in abs. DCM (0.15 M) was stirred at 0 °C for 30 minutes. The aldehyde was added over a period of
five minutes, and the mixture as stirred at 0 °C for one hour. After addition of water, the layers were
separated, and the aqueous layer was extracted with DCM (three times). The combined organic layers
were dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was
dry-loaded on silica and subjected to flash chromatography (silica, n-pentane/DCM).
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General procedure for synthesis of ynol ethers from vinyl dibromides (Second step)19:
A 15 mL pressure tube was charged with the phenol (6.7 mmol), 2,2'-bipyridine (310 mg, 2.0 mmol),
K3PO4 (6500 mg, 31.0 mmol), and copper(I) iodide (190 mg, 1.0 mmol); if solid, the 1,1-
dibromo-1-alkene (10.0 mmol) was also introduced at this stage. The tube was fitted with a rubber
septum, evacuated under high vacuum and backfilled with argon. Dry and degassed toluene (20 mL)
was next added as well as the 1,1-dibromo-1-alkene (10.0 mmol) which was added at this stage if
liquid. The rubber septum was replaced by a Teflon-coated screw cap and the heterogeneous
suspension heated at 110°C for 2 days, cooled to room temperature, diluted with dry dioxane (20 mL)
and treated with potassium tert-butoxide (1880 mg, 16.7 mmol). The resulting mixture was stirred
overnight at room temperature, filtered through a plug of silica gel (washed with EtOAc), and
concentrated in vacuo. The crude residue was purified by flash column chromatography.
1-(Hex-1-yn-1-yloxy)-3-methylbenzene (1a)23. 73% yield (919 mg, 93% purity, determined by GC);
colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.23–7.19 (m, 1H), 7.06–7.04 (m, 2H), 6.92 (d, J = 7.7 Hz,
1H), 2.36 (s, 3H), 2.28 (t, J = 6.9 Hz, 2H), 1.57–1.43 (m, 4H), 0.94 (t, J = 7.2 Hz, 3H).
(Hex-1-yn-1-yloxy)benzene (1b)23. 52% yield (610 mg, 95% purity, determined by GC); colorless oil;
1H NMR (400 MHz, CDCl3) δ 7.36–7.32 (m, 2H), 7.26–7.24 (m, 2H), 7.11 (t, J = 7.2 Hz, 1H), 2.28 (t,
J = 6.9 Hz, 2H), 1.58–1.43 (m, 4H), 0.94 (t, J = 7.2 Hz, 3H).
(Hex-1-yn-1-yloxy)benzene (1c)23. 68% yield (948 mg, 94% purity, determined by GC); colorless oil;
1H NMR (400 MHz, CDCl3) δ 7.33–7.27 (m, 2H), 7.23–7.14 (m, 2H), 2.27 (t, J = 7.0 Hz, 2H),
1.56–1.43 (m, 4H), 0.94 (t, J = 7.2 Hz, 3H).
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1-Methyl-3-(pent-4-en-1-yn-1-yloxy)benzene (1g)24. 85% yield (975 mg, 98% purity, determined by
GC); colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.25–7.20 (m, 1H), 7.08–7.06 (m, 2H), 6.93 (d, J =
7.6 Hz, 1H), 5.90 (m, 1H), 5.42–5.33 (m, 1H), 5.15–5.15 (m, 1H), 3.08–3.06 (m, 2H), 2.36 (s, 3H).
1-((Cyclohexylethynyl)oxy)-3-methylbenzene (1m)24. 77% yield (1104 mg, 94% purity, determined by
GC); colorless oil; 1H NMR (600 MHz, CDCl3) δ 7.24–7.19 (m, 1H), 7.06–7.05 (m, 2H), 6.92 (d, J =
7.6 Hz, 1H), 2.50–2.47 (m, 1H), 2.36 (s, 3H), 1.88–1.82 (m, 2H), 1.75–1.70 (m, 3H), 1.54–1.46 (m,
2H), 1.34–1.29 (m, 3H).
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General procedure for synthesis of alkynyl sulfides from terminal alkynes25:
o
To a THF solution of terminal alkynes (9.0 mmol), BuLi/Hex (8.5 mmol) was added at 0 C. The
mixture was stirred for 30 min. Dialkyl disulfides (8.0 mmol) was then added to the solution and the
mixture was stirred for 2 h. The reaction was quenched with 2-bromoethanol (10 mmol) and stirred for
an additional 2 h. Water (10 ml) was poured into the flask. The product was extracted with ethyl
acetate (20 ml x 3). The combined organic layer was washed with brine and then dried over Na2SO4
and concentrated in vacuo. The crude mixture was purified by silica gel column chromatography (with
hexane) to provide Alkynyl Sulfides.
Ethyl(phenylethynyl)sulfane (4b)26. 68% yield (991 mg, >99% purity, determined by GC); colorless oil;
1H NMR (400 MHz, CDCl3) δ 7.44–7.36 (m, 2H), 7.29–7.28 (m, 3H), 2.82 (q, J = 7.3 Hz, 2H), 1.45 (t,
J = 7.3 Hz, 3H).
Hex-1-yn-1-yl(phenyl)sulfane (4c)26. 62% yield (1060 mg, >99% purity, determined by GC); colorless
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oil; H NMR (600 MHz, CDCl3) δ 7.40 (d, J = 7.6 Hz, 2H), 7.32 (t, J = 7.7 Hz, 2H), 7.19 (t, J = 7.4
Hz, 1H), 2.45 (t, J = 7.1 Hz, 2H), 1.62–1.56 (m, 2H), 1.49–1.45 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H).
Dec-1-yn-1-yl(ethyl)sulfane (4f)26. 74% yield (1319 mg, >99% purity, determined by GC); colorless
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oil; H NMR (600 MHz, CDCl3) δ 2.68 (q, J = 7.3 Hz, 2H), 2.30 (t, J = 7.1 Hz, 2H), 1.54–1.49 (m,
2H), 1.39–1.36 (m, 4H), 1.32–1.25 (m, 9H), 0.88 (t, J = 7.0 Hz, 3H).
The starting material of 1d-1f, 1h-1l, 1n, 4a and 4d-4e have been prepared in our recent papers
(references 15c and 27).
General procedure for HOTf-catalyzed, solvent-free oxyarylation of ynol ethers:
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To a mixture of ynol ether 1a (47.0 mg, 0.25 mmol) and diphenyl sulfoxide 2a (101.0 mg, 0.5 mmol)
was added HOTf (3.8 mg, 0.025 mmol) under an air atmosphere. After stirring at 70 for 6 h, the
reaction mixture was quenched with NaHCO3 (50.0 mg), extracted with EtOAc, washed with brine,
dried over anhydrous Na2SO4, and concentrated. Column chromatography on silica gel
(EtOAc/petroleum ether = 1:100) gave 3aa as a colorless oil (81.9 mg, 84% yield).
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M-tolyl 2-(2-(phenylthio)phenyl)hexanoate (3aa). 1H NMR (600 MHz, CDCl3) δ 7.52 (dd, J = 7.8, 1.3
Hz, 1H), 7.47 (dd, J = 7.8, 1.3 Hz, 1H), 7.38–7.35 (m, 1H), 7.26–7.15 (m, 7H), 6.99–6.97 (m, 1H),
6.74–6.73 (m, 2H), 4.63 (t, J = 7.5 Hz, 1H), 2.30 (s, 3H), 2.19–2.13 (m, 1H), 1.79–1.74 (m, 1H),
1.38–1.22 (m, 4H), 0.85 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.6, 150.7, 141.7,
139.4, 137.1, 135.1, 133.9, 129.3, 129.1, 128.9, 128.9, 128.1, 128.0, 126.4, 126.3, 121.9, 118.3, 48.0,
33.3, 29.7, 22.5, 21.2, 13.9; HRMS (ESI) calcd for C25H26NaO2S (M + Na)+ 413.1551, found
413.1544.
M-tolyl 2-(5-methyl-2-(p-tolylthio)phenyl)hexanoate (3ab). 89% yield (93 mg); colorless oil; 1H NMR
(600 MHz, CDCl3) δ 7.36 (d, J = 7.9 Hz, 1H), 7.32–7.31 (m, 1H), 7.19–7.17 (m, 1H), 7.12–7.11 (m,
2H), 7.05–6.97 (m, 4H), 6.74–6.73 (m, 2H), 4.61 (t, J = 7.5 Hz, 1H), 2.35 (s, 3H), 2.30 (s, 3H), 2.26
(s, 3H), 2.16–2.10 (m, 1H), 1.75–1.70 (m, 1H), 1.35–1.28 (m, 4H), 0.85 (t, J = 7.2 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 172.8, 150.7, 141.5, 139.3, 138.9, 136.0, 135.0, 133.9, 130.8, 129.8, 129.3,
128.9, 128.6, 126.3, 121.9, 118.3, 47.8, 33.4, 29.7, 22.5, 21.3, 21.2, 20.9, 13.9; HRMS (ESI) calcd for
C27H30NaO2S (M + Na)+ 441.1864, found 441.1857.
M-tolyl 2-(5-chloro-2-((4-chlorophenyl)thio)phenyl)hexanoate (3ac). 71% yield (81 mg); colorless oil;
1H NMR (600 MHz, CDCl3) δ 7.54–7.53 (m, 1H), 7.40–7.39 (m, 1H), 7.25–7.23 (m, 1H), 7.21–7.20
(m, 3H), 7.13–7.12 (m, 2H), 7.01–7.00 (m, 1H), 6.73–6.71 (m, 2H), 4.54 (t, J = 7.5 Hz, 1H), 2.32 (s,
3H), 2.19–2.13 (m, 1H), 1.78–1.74 (m, 1H), 1.34–1.31 (m, 4H), 0.87 (t, J = 7.1 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 171.9, 150.5, 143.4, 139.5, 136.2, 135.4, 135.1, 132.6, 132.0, 130.4, 129.3,
129.0, 128.6, 128.4, 126.6, 121.8, 118.1, 48.0, 33.3, 29.6, 22.4, 21.2, 13.8; HRMS (ESI) calcd for
C25H24Cl2NaO2S (M + Na)+ 481.0772, found 481.0773.
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M-tolyl 2-(5-nitro-2-((4-nitrophenyl)thio)phenyl)hexanoate (3ad). 67% yield (80 mg); colorless oil;
1H NMR (600 MHz, CDCl3) δ 8.47–8.46 (m, 1H), 8.15–8.14 (m, 3H), 7.62–7.61 (m, 1H), 7.35–7.34
(m, 2H), 7.22–7.20 (m, 1H), 7.03–7.01 (m, 1H), 6.73–6.71 (m, 2H), 4.54 (t, J = 7.5 Hz, 1H), 2.31 (s,
3H), 1.97–1.89 (m, 1H), 1.39–1.24 (m, 5H), 0.89 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ
171.0, 150.2, 148.4, 146.6, 144.1, 143.2, 140.4, 139.8, 135.2, 131.1, 129.4, 129.2, 126.9, 124.6, 124.5,
123.8, 123.1, 121.5, 117.9, 48.4, 33.0, 29.6, 22.3, 21.2, 13.8; HRMS (ESI) calcd for C25H24N2NaO6S
(M + Na)+ 503.1253, found 503.1255.
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M-tolyl 2-(2-(methylthio)phenyl)hexanoate (3ae). 79% yield (65 mg); colorless oil; H NMR (600
MHz, CDCl3) δ 7.41 (d, J = 7.6 Hz, 1H), 7.35 (d, J = 7.8 Hz, 1H), 7.27–7.25 (m, 1H), 7.22–7.19 (m,
2H), 7.00–6.98 (m, 1H), 6.81–6.79 (m, 2H), 4.46 (t, J = 7.4 Hz, 1H), 2.49 (s, 3H), 2.31 (s, 3H),
2.19–2.15 (m, 1H), 1.86–1.80 (m, 1H), 1.43–1.32 (m, 4H), 0.90 (t, J = 7.1 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 172.7, 150.7, 139.4, 138.3, 137.6, 129.0, 128.0, 127.8, 127.2, 126.5, 126.1, 122.0,
118.4, 47.5, 33.0, 29.7, 22.5, 21.2, 17.2, 13.9; HRMS (ESI) calcd for C20H24NaO2S (M + Na)+
351.1395, found 351.1391.
M-tolyl 2-(5-methyl-2-(methylthio)phenyl)hexanoate (3af). 77% yield (66 mg); colorless oil; 1H NMR
(600 MHz, CDCl3) δ 7.30–7.29 (m, 1H), 7.23–7.19 (m, 2H), 7.08–7.06 (m, 1H), 6.99–6.98 (m, 1H),
6.82–6.80 (m, 2H), 4.50 (t, J = 7.5 Hz, 1H), 2.46 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H), 2.18–2.14 (m,
1H), 1.83–1.75 (m, 1H), 1.43–1.34 (m, 4H), 0.91 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ
172.8, 150.8, 139.4, 138.8, 136.4, 133.9, 129.4, 128.9, 128.6, 128.0, 126.4, 122.0, 118.4, 47.5, 33.2,
29.7, 22.5, 21.2, 21.0, 18.1, 13.9; HRMS (ESI) calcd for C21H26NaO2S (M + Na)+ 365.1551, found
365.1548.
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M-tolyl 2-(5-methoxy-2-(methylthio)phenyl)hexanoate (3ag). 83% yield (74 mg); colorless oil; H
NMR (600 MHz, CDCl3) δ 7.44 (d, J = 8.6 Hz, 1H), 7.22–7.20 (m, 1H), 7.01–6.99 (m, 2H), 6.83–6.80
(m, 3H), 4.63 (t, J = 7.5 Hz, 1H), 3.80 (s, 3H), 2.43 (s, 3H), 2.32 (s, 3H), 2.18–2.15 (m, 1H),
1.84–1.78 (m, 1H), 1.42–1.32 (m, 4H), 0.90 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.7,
159.2, 150.7, 141.9, 139.5, 133.4, 129.0, 128.0, 126.5, 122.0, 118.3, 113.6, 113.1, 55.4, 48.0, 33.4,
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29.7, 22.6, 21.3, 19.7, 13.9; HRMS (ESI) calcd for C21H26NaO3S (M + Na)+ 381.1500, found
381.1486.
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M-tolyl 2-(5-chloro-2-(methylthio)phenyl)hexanoate（3ah). 70% yield (63 mg); colorless oil; 1H NMR
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(600 MHz, CDCl3) δ 7.42–7.41 (m, 1H), 7.29–7.21 (m, 3H), 7.02–7.00 (m, 1H), 6.82–6.81 (m, 2H),
4.42 (t, J = 7.5 Hz, 1H), 2.48 (s, 3H), 2.33 (s, 3H), 2.20–2.15 (m, 1H), 1.83–1.81 (m, 1H), 1.40–1.38
(m, 4H), 0.91 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.1, 150.6, 139.9, 139.5, 136.2,
132.1, 129.4, 129.0, 127.9, 127.5, 126.6, 121.9, 118.3, 47.5, 33.0, 29.7, 22.5, 21.2, 17.4, 13.9; HRMS
(ESI) calcd for C20H23ClNaO2S (M + Na)+ 385.1005, found 385.1002.
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M-tolyl 2-(5-formyl-2-(methylthio)phenyl)hexanoate（3ai). 75% yield (67 mg); colorless oil; 1H NMR
(400 MHz, CDCl3) δ 9.95 (s, 1H), 7.91 (d, J = 1.7 Hz, 1H), 7.78 (dd, J = 8.2, 1.8 Hz, 1H), 7.35 (d, J =
8.2 Hz, 1H), 7.22 (t, J = 8.0 Hz, 1H), 7.01 (d, J = 7.4 Hz, 1H), 6.82–6.81 (m, 2H), 4.32 (t, J = 7.1 Hz,
1H), 2.58 (s, 3H), 2.32 (s, 3H), 2.27–2.20 (s, 1H), 1.97–1.87 (m, 1H), 1.47–1.33 (m, 4H), 0.92 (t, J =
7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 191.4, 171.9, 150.6, 146.9, 139.6, 137.0, 133.2, 129.0,
128.7, 128.4, 126.7, 124.8, 121.9, 118.3, 47.2, 32.6, 29.7, 22.5, 21.2, 15.5, 13.9; HRMS (ESI) calcd
for C21H24NaO3S (M + Na)+ 379.1344, found 379.1352.
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M-tolyl 2-(2-(isopropylthio)phenyl)hexanoate (3aj). 92% yield (82 mg); colorless oil; H NMR (600
MHz, CDCl3) δ 7.55 (dd, J = 7.7, 0.9 Hz, 1H), 7.47 (dd, J = 7.7, 1.1 Hz, 1H), 7.30–7.29 (m, 1H),
7.28–7.19 (m, 2H), 7.00–6.98 (m, 1H), 6.80–6.77 (m, 2H), 4.77 (t, J = 7.5 Hz, 1H), 3.41–3.37 (m,
1H), 2.31 (s, 3H), 2.21–2.13 (m, 1H), 1.81–1.76 (m, 1H), 1.42–1.35 (m, 4H), 1.32 (d, J = 6.7 Hz, 3H),
1.29 (d, J = 6.6 Hz, 3H), 0.90 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.9, 150.8, 141.7,
139.4, 135.1, 134.2, 129.0, 127.9, 127.4, 127.4, 126.4, 121.9, 118.3, 47.7, 39.7, 33.5, 29.7, 23.2, 23.1,
22.6, 21.2, 13.9; HRMS (ESI) calcd for C22H28NaO2S (M + Na)+ 379.1708, found 379.1701.
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M-tolyl 2-(2-(methylthio)pyridin-3-yl)hexanoate (3ak). 81% yield (67 mg); colorless oil; H NMR
(600 MHz, CDCl3) δ 8.41 (dd, J = 4.8, 1.6 Hz, 1H), 7.63 (dd, J = 7.7, 1.6 Hz, 1H), 7.23–7.21 (t, J =
7.7 Hz, 1H), 7.05–7.01 (m, 2H), 6.83–6.81 (m, 2H), 4.16 (t, J = 7.5 Hz, 1H), 2.62 (s, 3H), 2.33 (s,
3H), 2.18–2.14 (m, 1H), 1.90–1.84 (m, 1H), 1.42–1.38 (m, 4H), 0.92 (t, J = 7.0 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 172.0, 158.5, 150.6, 147.9, 139.5, 134.0, 132.3, 129.0, 126.7, 121.9, 119.3,
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118.3, 46.5, 32.6, 29.7, 22.4, 21.2, 13.9, 13.5; HRMS (ESI) calcd for C19H23NNaO2S (M + Na)+
352.1347, found 352.1346.
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Phenyl 2-(2-(phenylthio)phenyl)hexanoate (3ba). 80% yield (75 mg); colorless oil; H NMR (400
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(t, J = 7.5 Hz, 1H), 2.18–2.12 (m, 1H), 1.82–1.74 (m, 1H), 1.39–1.22 (m, 4H), 0.85 (t, J = 7.0 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 172.5, 150.8, 141.6, 137.0, 135.1, 133.9, 129.3, 129.2, 129.0,
128.9, 128.0, 128.0, 126.3, 125.6, 121.3, 48.0, 33.3, 29.7, 22.5, 13.9; HRMS (ESI) calcd for
C24H24NaO2S (M + Na)+ 399.1395, found 399.1392.
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4-chlorophenyl 2-(2-(phenylthio)phenyl)hexanoate (3ca). 68% yield (70 mg); colorless oil; H NMR
(600 MHz, CDCl3) δ 7.50–7.47 (m, 2H), 7.38–7.35 (m, 2H), 7.26–7.16 (m, 7H), 6.86–6.85 (m, 2H),
4.63 (t, J = 7.4 Hz, 1H), 2.18–2.11 (m, 1H), 1.80–1.74 (m, 1H), 1.40–1.27 (m, 4H), 0.85 (t, J = 7.0 Hz,
3H); 13C NMR (150 MHz, CDCl3) δ 172.3, 149.2, 141.3, 136.9, 135.2, 133.8, 131.0, 129.2, 129.2,
129.1, 129.0, 128.1, 128.0, 126.3, 122.7, 47.9, 33.1, 29.6, 22.4, 13.9; HRMS (ESI) calcd for
C24H23ClNaO2S (M + Na)+ 433.1005, found 433.1008.
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Phenyl 2-(2-(phenylthio)phenyl)acetate (3da). 81% yield (65 mg); white soild, mp: 105–107 C; H
NMR (600 MHz, CDCl3) δ 7.45–7.42 (m, 2H), 7.34–7.31 (m, 3H), 7.29–7.18 (m, 7H), 7.03–7.02 (m,
2H), 4.06 (s, 2H); 13C NMR (150 MHz, CDCl3) δ 169.6, 150.8, 136.4, 136.4, 134.6, 134.3, 131.2,
129.3, 129.3, 129.2, 128.6, 128.5, 126.4, 125.7, 121.4, 39.8; HRMS (ESI) calcd for C20H16NaO2S (M
+ Na)+ 343.0769, found 343.0763.
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M-tolyl 2-(2-(phenylthio)phenyl)acetate (3ea). 84% yield (70 mg); colorless oil; H NMR (600 MHz,
CDCl3) δ 7.46–7.42 (m, 2H), 7.35–7.32 (m, 1H), 7.28–7.18 (m, 7H), 7.00–6.99 (m, 1H), 6.83–6.81
(m, 2H), 4.05 (s, 2H), 2.30 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.7, 150.7, 139.4, 136.5, 136.5,
134.7, 134.2, 131.2, 129.2, 129.1, 129.0, 128.6, 128.5, 126.5, 126.4, 122.0, 118.3, 39.8, 21.2; HRMS
(ESI) calcd for C21H18NaO2S (M + H)+ 357.0925, found 357.0919.
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Phenyl 2-(2-(phenylthio)phenyl)pent-4-enoate (3fa). 81% yield (73 mg); colorless oil; H NMR (600
MHz, CDCl3) δ 7.52 (dd, J = 7.8, 1.2 Hz, 1H), 7.48–7.47 (m, 1H), 7.38–7.35 (m, 1H), 7.32–7.26 (m,
3H), 7.24–7.16 (m, 6H), 6.94–6.93 (m, 2H), 5.82–5.75 (m, 1H), 5.08–5.05 (m, 1H), 5.02–5.00 (m,
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1H), 4.76 (q, J = 6.8 Hz, 1H), 2.91–2.86 (m, 1H), 2.53–2.50 (m, 1H); 13C NMR (150 MHz, CDCl3) δ
171.9, 150.7, 140.8, 136.9, 135.1, 134.8, 133.9, 129.3, 129.2, 129.1, 128.9, 128.2, 128.1, 126.4, 125.7,
121.3, 117.4, 47.8, 37.5; HRMS (ESI) calcd for C23H21O2S (M + H)+ 361.1257, found 361.1251.
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M-tolyl 2-(2-(phenylthio)phenyl)pent-4-enoate (3ga). 83% yield (78 mg); colorless oil; H NMR (600
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MHz, CDCl3) δ 7.53 (dd, J = 7.8, 1.3 Hz, 1H), 7.48 (dd, J = 7.8, 1.2 Hz, 1H), 7.39–7.36 (m, 1H),
7.27–7.22 (m, 5H), 7.20–7.15 (m, 2H), 6.99–6.98 (m, 1H), 6.74–6.73 (m, 2H), 5.80–5.76 (m, 1H),
5.08–5.00 (m, 2H), 4.74 (q, J = 6.8 Hz, 1H), 2.91–2.86 (m, 1H), 2.54–2.49 (m, 1H), 2.30 (s, 3H); 13
C
NMR (150 MHz, CDCl3) δ 171.9, 150.7, 140.9, 139.4, 136.9, 135.1, 134.9, 133.9, 129.3, 129.1, 128.9,
128.9, 128.2, 128.2, 126.5, 126.3, 121.9, 118.3, 117.4, 47.9, 37.5, 21.2; HRMS (ESI) calcd for
C24H22NaO2S (M + Na)+ 397.1238, found 397.1220.
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Naphthalen-2-yl 2-(2-(phenylthio)phenyl)pent-4-enoate (3ha). 73% yield (75 mg); colorless oil; H
NMR (600 MHz, CDCl3) δ 7.80–7.76 (m, 2H), 7.73–7.72 (m, 1H), 7.58–7.56 (m, 1H), 7.51–7.50 (m,
1H), 7.48–7.35 (m, 5H), 7.28–7.22 (m, 3H), 7.18–7.16 (m, 1H), 7.08–7.06 (m, 1H), 5.84–5.81 (m,
1H), 5.11–5.03 (m, 2H), 4.82 (q, J = 7.0 Hz, 1H), 2.95–2.92 (m, 1H), 2.58–2.53 (m, 1H); 13C NMR
(150 MHz, CDCl3) δ 172.0, 148.3, 140.8, 136.9, 135.2, 134.9, 133.6, 131.3, 129.3, 129.2, 129.1,
129.0, 128.3, 128.2, 127.7, 127.6, 126.4, 126.4, 125.6, 120.9, 118.3, 117.5, 47.9, 37.5; HRMS (ESI)
calcd for C27H22NaO2S (M + H)+ 433.1238, found 433.1237.
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M-tolyl 2-phenyl-2-(2-(phenylthio)phenyl)acetate (3ia). 78% yield (80 mg); colorless oil; H NMR
(600 MHz, CDCl3) δ 7.48 (dd, J = 7.7, 1.2 Hz, 1H), 7.38–7.30 (m, 7H), 7.28–7.24 (m, 3H), 7.22–7.17
(m, 4H), 7.00–6.99 (m, 1H), 6.80–6.78 (m, 2H), 5.92 (s, 1H), 2.31 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ 171.0, 150.7, 141.1, 139.4, 137.5, 136.7, 135.1, 133.7, 129.9, 129.2, 129.1, 129.0, 128.9,
128.8, 128.8, 128.4, 127.5, 126.6, 126.4, 121.9, 118.3, 54.2, 21.2; HRMS (ESI) calcd for
C27H22NaO2S (M + Na)+ 433.1238, found 433.1229.
Ethyl 2-phenyl-2-(2-(phenylthio)phenyl)acetate (3ja). 66% yield (57 mg); colorless oil; 1H NMR (600
MHz, CDCl3) δ 7.44–7.42 (m, 1H), 7.35–7.30 (m, 3H), 7.25–7.22 (m, 7H), 7.17–7.14 (m, 3H), 5.72
(s, 1H), 4.11 (q, J = 7.1 Hz, 2H), 1.18 (t, J = 7.0 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 172.3,
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141.4, 138.1, 136.8, 134.9, 133.6, 129.8, 129.1, 129.0, 128.8, 128.6, 128.5, 128.1, 127.1, 126.2, 61.2,
54.1, 14.0; HRMS (ESI) calcd for C22H20NaO2S (M + Na)+ 371.1082, found 371.1079.
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Ethyl 2-(2-(phenylthio)phenyl)-2-(4-(trifluoromethyl)phenyl)acetate (3ka). 68% yield (72 mg);
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colorless oil; H NMR (600 MHz, CDCl3) δ 7.52–7.51 (m, 2H), 7.46–7.45 (m , 1H), 7.39–7.33 (m,
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4H), 7.26–7.21 (m, 3H), 7.17–7.16 (m, 1H), 7.10–7.09 (m, 2H), 5.79 (s, 1H), 4.15–4.13 (m, 2H), 1.20
(t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 171.7, 142.0, 140.5, 136.4, 135.3, 133.7, 129.5,
129.3, 129.1, 129.0, 128.9, 128.5, 126.4, 125.4 (q, J = 3.7 Hz), 61.5, 53.8, 14.0; 19F NMR (565 MHz,
CDCl3) δ –62.6; HRMS (ESI) calcd for C23H19F3NaO2S (M + Na)+ 439.0956, found 439.0957.
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M-tolyl 4-phenyl-2-(2-(phenylthio)phenyl)butanoate (3la). 64% yield (70 mg); colorless oil; H NMR
(600 MHz, CDCl3) δ 7.53 (dd, J = 7.8, 1.2 Hz, 1H), 7.49 (dd, J = 7.8, 1.2 Hz, 1H), 7.38–7.35 (m, 1H),
7.26–7.22 (m, 4H), 7.21–7.15 (m, 6H), 7.12–7.11 (m, 2H), 6.99–6.97 (m, 1H), 6.74–6.73 (m, 2H),
4.68 (q, J = 6.7 Hz, 1H), 2.73–2.68 (m, 1H), 2.58–2.54 (m, 1H), 2.50–2.46 (m, 1H), 2.30 (s, 3H),
2.09–2.04 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 172.3, 150.6, 141.4, 141.3, 139.4, 137.0, 135.2,
131.0, 129.2, 129.1, 129.0, 128.9, 128.4, 128.3, 128.2, 128.1, 126.5, 126.3, 125.9, 121.9, 118.3, 47.8,
35.2, 33.8, 21.2; HRMS (ESI) calcd for C29H26NaO2S (M + Na)+ 461.1551, found 461.1544.
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M-tolyl 2-cyclohexyl-2-(2-(phenylthio)phenyl)acetate (3ma). 65% yield (68 mg); colorless oil; H
NMR (600 MHz, CDCl3) δ 7.67–7.66 (m, 1H), 7.44–7.43 (m, 1H), 7.36–7.32 (m, 1H), 7.24–7.22 (m,
5H), 7.17–7.15 (m, 2H), 6.97–6.96 (m, 1H), 6.71–6.70 (m, 2H), 4.53 (d, J = 10.4 Hz, 1H), 2.29 (s,
3H), 2.17–2.13 (m, 1H), 2.04–2.02 (m, 1H), 1.82–1.77 (m, 1H), 1.65–1.64 (m, 2H), 1.36–1.31 (m,
2H), 1.26–1.24 (m, 1H), 1.19–1.13 (m, 2H), 0.94–0.88 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 172.3,
150.6, 139.9, 139.3, 137.2, 135.0, 134.7, 129.6, 129.0, 128.9, 128.7, 128.4, 127.9, 126.4, 126.3, 122.0,
118.3, 53.8, 41.9, 31.9, 29.9, 26.2, 26.1, 26.0, 21.2; HRMS (ESI) calcd for C27H28NaO2S (M + Na)+
439.1708, found 439.1694.
4-chlorophenyl 2-cyclohexyl-2-(2-(phenylthio)phenyl)acetate (3na). 60% yield (65 mg); colorless oil;
1H NMR (600 MHz, CDCl3) δ 7.64–7.62 (m, 1H), 7.45–7.44 (m, 1H), 7.37–7.32 (m, 2H), 7.26–7.22
(m, 6H), 7.16–7.14 (m, 1H), 6.84–6.82 (m, 2H), 4.52 (d, J = 10.4 Hz, 1H), 2.14–2.11 (m, 1H),
2.00–1.97 (m, 1H), 1.79–1.77 (m, 1H), 1.64–1.62 (m, 2H), 1.35–1.25 (m, 3H), 1.19–1.14 (m, 2H),
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0.95–0.87 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 172.1, 149.1, 139.6, 137.1, 135.0, 134.8, 130.9,
129.5, 129.2, 129.1, 128.8, 128.4, 128.1, 126.3, 122.8, 53.7, 41.8, 31.9, 29.9, 26.2, 26.1, 26.0; HRMS
(ESI) calcd for C26H25ClNaO2S (M + Na)+ 459.1161, 459.1155.
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Ethyl 2-(2-(phenylthio)phenyl)acetate (3oa). 83% yield (56 mg); colorless oil; H NMR (600 MHz,
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CDCl3) δ 7.41 (dd, J = 7.7, 1.0 Hz, 1H), 7.33 (dd, J = 7.6, 1.4 Hz, 1H), 7.31–7.28 (m, 1H), 7.25–7.22
(m, 3H), 7.17–7.14 (m, 3H), 4.08 (q, J = 7.1 Hz, 2H), 3.83 (s, 2H), 1.20 (t, J = 7.1 Hz, 3H); 13C NMR
(150 MHz, CDCl3) δ 171.1, 136.9, 136.6, 134.5, 134.2, 131.0, 129.2, 129.0, 128.4, 128.2, 126.3, 60.8,
39.7, 14.1; HRMS (ESI) calcd for C16H16NaO2S (M + Na)+ 295.0769, found 295.0766.
General procedure for HOTf-catalyzed, solvent-free oxyarylation of thioethers:
To a mixture of thioalkyne 4a (52.5 mg, 0.25 mmol) and diphenyl sulfoxide 2a (101.0 mg, 0.5 mmol)
was added HOTf (3.8 mg, 0.025 mmol) under an air atmosphere. After stirring at 70 for 1 h, the
reaction mixture was quenched with NaHCO3 (50.0 mg), extracted with EtOAc, washed with brine,
dried over anhydrous Na2SO4, and concentrated. Column chromatography on silica gel
(EtOAc/petroleum ether = 1:50) gave 5aa (86.5 mg, 84% yield) as a colorless oil.
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S-phenyl 2-phenyl-2-(2-(phenylthio)phenyl)ethanethioate (5aa). H NMR (600 MHz, CDCl3) δ 7.46
(dd, J = 7.7, 1.3 Hz, 1H), 7.41 (dd, J = 7.8, 1.4 Hz, 1H), 7.36–7.29 (m, 10H), 7.28–7.26 (m, 4H),
7.20–7.18 (m, 3H), 6.05 (s, 1H); 13C NMR (150 MHz, CDCl3) δ 196.9, 140.6, 137.4, 136.8, 135.2,
134.4, 133.9, 130.1, 129.3, 129.2, 129.2, 129.2, 129.1, 128.7, 128.7, 128.5, 128.0, 127.5, 126.4, 61.5;
HRMS (ESI) calcd for C26H20NaOS2 (M + Na)+ 435.0853, found 435.0859.
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S-ethyl 2-phenyl-2-(2-(phenylthio)phenyl)ethanethioate (5ba). 77% yield (70 mg); colorless oil; H
NMR (600 MHz, CDCl3) δ 7.42 (dd, J = 7.8, 1.3 Hz, 1H), 7.40 (dd, J = 7.9, 1.4 Hz, 1H), 7.30–7.27
(m, 3H), 7.24–7.21 (m, 6H), 7.17–7.15 (m, 3H), 5.92 (s, 1H), 2.84 (q, J = 7.4 Hz, 2H), 1.19 (t, J = 7.4
Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 198.9, 140.7, 137.8, 136.7, 134.9, 134.1, 129.9, 129.3, 129.1,
129.1, 128.5, 128.5, 128.3, 127.3, 126.3, 61.8, 24.0, 14.4; HRMS (ESI) calcd for C22H20NaOS2 (M +
Na)+ 387.0853, found 387.0859.
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S-phenyl 2-(2-(phenylthio)phenyl)hexanethioate (5ca). 92% yield (90 mg); colorless oil; H NMR
(600 MHz, CDCl3) δ 7.48–7.45 (m, 2H), 7.35–7.34 (m, 4H), 7.30–7.23 (m, 7H), 7.20–7.17 (m, 1H),
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4.73 (t, J = 7.4 Hz, 1H), 2.17–2.11 (m, 1H), 1.73–1.71 (m, 1H), 1.26–1.14 (m, 4H), 0.81 (t, J = 7.1 Hz,
3H); 13C NMR (150 MHz, CDCl3) δ 198.4, 140.7, 136.9, 134.9, 134.3, 134.2, 129.4, 129.1, 129.1,
129.0, 128.8, 128.5, 128.1, 128.0, 126.4, 56.0, 33.6, 29.5, 22.4, 13.8; HRMS (ESI) calcd for
C24H24NaOS2 (M + Na)+ 415.1166, found 415.1174.
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S-methyl 2-(2-(phenylthio)phenyl)hexanethioate (5da). 91% yield (75 mg); colorless oil; H NMR
(600 MHz, CDCl3) δ 7.45 (dd, J = 7.9, 1.3 Hz, 1H), 7.41 (dd, J = 7.8, 1.2 Hz, 1H), 7.33–7.31 (m, 1H),
7.28–7.27 (m, 1H), 7.26–7.25 (m, 1H), 7.23–7.19 (m, 4H), 4.63 (t, J = 7.4 Hz, 1H), 2.22 (s, 3H),
2.14–2.08 (m, 1H), 1.73–1.68 (m, 1H), 1.25–1.22 (m, 4H), 0.81 (t, J = 7.2 Hz, 3H); 13C NMR (150
MHz, CDCl3) δ 200.8, 140.9, 136.9, 134.7, 134.4, 129.6, 129.1, 128.7, 128.3, 128.0, 126.4, 56.1, 33.4,
29.5, 22.5, 13.8, 11.9; HRMS (ESI) calcd for C19H22NaOS2 (M + Na)+ 353.1010, found 353.1008.
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S-ethyl 2-(2-(phenylthio)phenyl)octanethioate (5ea). 95% yield (88 mg); colorless oil; H NMR (600
MHz, CDCl3) δ 7.44 (dd, J = 7.9, 1.3 Hz, 1H), 7.42 (dd, J = 7.8, 1.2 Hz, 1H), 7.33–7.30 (m, 1H),
7.27–7.16 (m, 6H), 4.60 (t, J = 7.4 Hz, 1H), 2.84–2.76 (m, 2H), 2.10–2.08 (m, 1H), 1.70–1.67 (m,
1H), 1.20–1.16 (m, 11H), 0.83 (t, J = 7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 200.5, 141.0, 137.0,
134.8, 134.2, 129.5, 129.0, 128.6, 128.3, 127.9, 126.3, 56.2, 33.6, 31.5, 29.0, 27.3, 23.5, 22.5, 14.5,
14.0; HRMS (ESI) calcd for C22H28NaOS2 (M + Na)+ 395.1479, found 395.1491.
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S-ethyl 2-(2-(phenylthio)phenyl)decanethioate (5fa). 96% yield (96 mg); colorless oil; H NMR (600
MHz, CDCl3) δ 7.45–7.42 (m, 2H), 7.33–7.30 (m, 1H), 7.26–7.18 (m, 6H), 4.60 (t, J = 7.4 Hz, 1H),
2.83–2.77 (m, 2H), 2.10–2.08 (m, 1H), 1.69–1.67 (m, 1H), 1.30–1.15 (m, 15H), 0.87–0.85 (m, 3H);
13C NMR (150 MHz, CDCl3) δ 200.5, 141.0, 137.0, 134.8, 134.2, 129.5, 129.0, 128.6, 128.3, 127.9,
126.3, 56.2, 33.6, 31.8, 29.3, 29.3, 29.1, 27.3, 23.5, 22.6, 14.5, 14.1; HRMS (ESI) calcd for
C24H32NaOS2 (M + Na)+ 423.1792, found 423.1784.
General procedure for the synthesis of multifunctional aldehyde and ketone from thioester:
To a reaction vessel was added thioester 5fa (100 mg, 0.25 mmol), acetone (2 ml), triethylsilane (87.2
mg, 0.75 mmol) and Pd/C (4.4 mg, 0.0125 mmol) and the mixture was stirred for 10 h at rt. Et2O (15
mL) was added and the suspension was washed with water (10 mL). The organic layer was dried over
MgSO4, filtered, and evaporated. Column chromatography on silica gel (EtOAc/petroleum ether =
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2-(2-(phenylthio)phenyl)decanal (6). 79% yield (67.2 mg); colorless oil; H NMR (600 MHz, CDCl3)
δ 9.57 (s, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.29–7.25 (m, 3H), 7.20–7.16 (m,
4H), 4.28 (t, J = 7.0 Hz, 1H), 2.12–2.05 (m, 1H), 1.67–1.63 (m, 1H), 1.28–1.16 (m, 12H), 0.86 (t, J =
7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 200.6, 139.6, 136.8, 135.2, 134.7, 129.3, 129.2, 129.2,
128.9, 128.3, 126.5, 55.9, 31.8, 29.9, 29.5, 29.3, 29.2, 27.1, 22.6, 14.1; HRMS (ESI) calcd for
C22H28NaOS (M + Na)+ 363.1759, found 363.1764.
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Thioester 5fa (100 mg, 0.25 mmol), Cu (I) thiophene-2-carboxylate (71.6 mg, 0.375 mmol), boronic
acid (33.6 mg, 0.275 mmol), Pd2dba3.CHCl3 (2.6 g, 0.0025 mmol) and tris-2-furylphosphine (1.7 g,
0.0075 mmol) were placed in a reaction vessel that was flushed with argon. Acetone (5 mL) was
added and the mixture was stirred for 18 h at 50 °C. Et2O (15 mL) was added and the suspension was
washed with 5% aq. HCl (10 mL) and water (10 mL). The organic layer was dried over MgSO4,
filtered, and evaporated. Column chromatography on silica gel (EtOAc/petroleum ether = 1:50) gave 7
(78.2 mg, 75% yield) as a colorless oil.
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1-phenyl-2-(2-(phenylthio)phenyl)decan-1-one (7). 75% yield (78.2 mg); colorless oil; H NMR (400
MHz, CDCl3) δ 8.01–7.93 (m, 2H), 7.44 (t, J = 7.4 Hz, 1H), 7.39 (dd, J = 7.7, 1.3 Hz, 1H), 7.32–7.28
(m, 4H), 7.26–7.18 (m, 5H), 7.16–7.12 (m, 1H), 5.32 (dd, J = 8.0, 6.0 Hz, 1H), 2.19–2.08 (m, 1H),
1.60–1.56 (m, 1H), 1.33–1.16 (m, 12H), 0.86 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 200.3,
142.0, 136.9, 136.5, 134.7, 133.3, 132.8, 129.7, 129.7, 129.2, 128.7, 128.4, 128.4, 127.6, 126.6, 49.9,
34.2, 31.8, 29.6, 29.4, 29.2, 27.9, 22.6, 14.1; HRMS (ESI) calcd for C28H32NaOS (M + Na)+ 439.2072,
found 439.2067.
ACKNOWLEDGMENTS
We are grateful for the financial support from the Science Technology Department of Zhejiang
Province (2015C31030), Natural Science Foundation of Zhejiang Province (LR12B02001 and
LY14B020002), and National Natural Science Foundation of China (21172199).
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Supporting Information: Detailed experimental procedures for Scheme 2. Copies of H NMR
spectra of compounds 1a-1c, 1g, 1m, 4b-4c, 4f, H NMR, 13C NMR spectra of compounds 3aa-3ak,
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3ba-3oa, 5aa-5fa, 6 and 7. This material is available free of charge via the Internet at
http://pubs.acs.org.
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REFERENCES
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(18) During the submission of this manuscript, Maulide reported the synthesis of α-arylated ketones
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