NH4I-Promoted and H2O-Controlled Intermolecular Bis-sulfenylation and Hydroxysulfenylation of Alkenes via a Radical Process

Article abstract of DOI:10.1021/acs.joc.9b01047

An NH₄I-promoted and H₂O-controlled intermolecular difunctionalization of alkenes for the synthesis of bis-methylsulfane and β-hydroxysulfides is presented. Mechanistic investigation revealed the reaction proceeds via methylthiyl radical addition to C=C of alkenes to give a carbon-centered radical and immediately cyclize to a thiiranium ion, followed by combination with H₂O to afford β-hydroxysulfides in 52-89% yields with chemo- and regioselectivities. In the absence of water, 1,2-disulfenylation takes place to give bis-methylsulfane in moderate to good yields.

Full text of DOI:10.1021/acs.joc.9b01047

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Note
NH4I-Promoted and H2O-Controlled Intermolecular Bis-sulfenylation
and Hydroxysulfenylation of Alkenes via a Radical Process
Runfa He, Xiuwen Chen, Yibiao Li, Qiang Liu, Chunshu Liao, Lu Chen, and Yubing Huang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01047 • Publication Date (Web): 11 Jun 2019
Downloaded from http://pubs.acs.org on June 11, 2019
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NH4I-Promoted and H2O-Controlled Intermolecular Bis-sulfenylation and
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Hydroxysulfenylation of Alkenes via a Radical Process
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Runfa Hea, Xiuwen Chena, Yibiao Lia*, Qiang Liua,b, Chunshu Liaoa, Lu Chen*, Yubing Huang
aSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, Guangdong Province
529090, China; bCenter of Basic Molecular Science, Department of Chemistry, Tsinghua University,
Beijing 100084, China
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E-mail: leeyib268@126.com; wyuchemcl@126.com
OH
SMe
NH4I
+
or
or
DMSO
R
R
SMe
SMe
O
R
R
SMe
H2O-Controlled
15 examples
Up to 86% yield
15 examples
Up to 89% yield
6 examples
Up to 92% yield
ABSTRACT: An NH4I-promoted and H2O-controlled intermolecular difunctionalization of alkenes
for the synthesis of bis-methylsulfane and β-hydroxysulfides is presented. Mechanistic investigation
revealed the reaction proceeds via methylthiyl radical addition to C=C double bond of alkenes to
give a carbon-centered radical and immediately cyclize to a thiiranium ion, followed by combination
with H2O to afford β-hydroxysulfides in 52–89% yield with chemo- and regioselectivity. In the
absence of the water, 1,2-disulfenylation takes place to give bis-methylsulfane in moderate to good
yields.
In recent decades, the difunctionalization of olefins has become one of the most practical
methods for synthesizing functional molecules or organic synthons bearing two vicinal
carbon−carbon bonds or carbon−heteroatom bonds.[1] Among them, the bis-sulfenylation[2]
and hydroxysulfenylation[3] of allylbenzene derivatives to prepare synthetically useful vicinal
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dithioethers is attracting increasing attention due to their synthetic utility in drug
development[4] and fine chemical synthesis[5]. Previously reported sulfur etherification
reagents mainly focused on alkyl and aromatic sulphides, such as thiol,[6] sulfonyl
hydrazides,[7] disulfides,[8] sulfonamides,[9] sulfenyl halides,[10] sulfenate esters,[11]
(methylthio)-sulfonium salts[12] and sodium methanethiolate.[13] In particular, Lei and
co-workers developed that the first efficiently electrocatalytic dehydrogenative C−H/S−H
cross-coupling construct C-S bond, which was use the aryl/heteroaryl thiols and electron-rich
arenes as reaction substrates.[14] Simultaneously, Jiang and co-workers use the organic
thiosulfate salts to adjust the nature of free radicals by using the “masked strategy” and
achieve selective sulphoxide and thioetherification.[15] However, these systems involve
unpleasant odors, expensive catalysts and reagents, low chemo- and regio-selectivity and
harsh conditions. There are hardly any reports of the use of dimethyl sulfoxide (DMSO) as a
sulfur etherification reagent in bis-sulfenylation and hydroxysulfenylation reactions of
alkenes. DMSO, however, has been used as source of groups such as –C1, –CH2–, =CH–, –
CH3, –CHO, –CN, –SMe, –SO2Me group and as an oxygen source[16] in various organic
synthesis methodology over recent decades. In addition, most bis-sulfenylation reactions are
generally initiated through an episulfonium ion intermediate, with nucleophilic attack
ultimately leading to vicinal dithioethers (Scheme 1a)[2a-e ,17]. In contrast, the bis-sulfenylation
of alkenes to give vicinal dithioethers via a radical approach has rarely been explored. When
the bis-sulfenylation reaction was initiated through a CH3S• radical originating from DMSO,
a subsequent carbon radical intermediate was formed. Herein, we report the realization of this
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hypothesis via an NH4I-promoted and H2O-controlled intermolecular bis-sulfenylation and
hydroxysulfenylation reaction of alkenes with DMSO as a MeS radical surrogate (Scheme
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1b).
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Reported work:
R2S
R1
SMe
SR2
R1
R1
R2
S
+
(a)
R2S
(from RSSR)
R1
R1
R1
cationic intermediate
This work:
SMe
SMe
R
R
or
R
+
(b)
SMe
OH
CH3S
(from DMSO)
radical intermediate
R
Scheme 1. Outline for the Bis-sulfenylation and Hydroxysulfenylation of Alkenes
In order to test the above bis-sulfenylation hypothesis, we screened reaction conditions
using allylbenzene 1a, NH4I and anhydrous DMSO as a model reaction. The DMSO was
used as both solvent and a MeS radical surrogate. To our delight, at a reaction temperature of
100 °C, the bis-sulfenylation reaction proceeded to afford the vicinal dithioether product 2a
in 19% yield, along with a small amount of the hydroxysulfenylation product 3a in the
presence of 2 equiv. NH4I (Table 1, entry 1). Further studies demonstrated that the yield was
significantly improved upon increasing the reaction temperature (Table 1, entries 2−4). When
the reaction temperature was increased to 140 °C, the yield of the bis-sulfenylation product
2a was slightly lower, and the yield of the hydroxysulfenylation product 3a was slightly
increased to 15% (Table 1, entry 5). Increasing or decreasing the amount of NH4I did not
improve the yield of the bis-sulfenylation reaction (Table 1, entries 6-7). It is noteworthy that
H2O concentration had a significant effect on the yield of 2a and 3a (Table 1, entries 8−12).
The yield of the hydroxysulfenylation product 3a was greatly improved if DMSO and H2O
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were used as the reaction solvent. We observed that when the ratio of DMSO: H2O was 1:1,
the hydroxysulfenylation product was afforded in 87% yield and the yield of the
bis-sulfenylation reaction did not exceed 5% (Table 1, entries 8-12). Subsequently, we
investigated various halide sources, such as Et4NI, NH4Br and HI (Table 1, entries 15-17).
None of these promoted the reaction well, and only I2 generated the
1-(methylthio)-3-phenylpropan-2-ol 3a in 53% yield (Table 1, entry 18). When
2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or butylated hydroxytoluene (BHT) were
added as radical scavengers, the sulfenylation reaction was completely inhibited (Table 1,
entries 19-20). This indicates that the current intermolecular difunctionalization reaction
proceeds via a radical pathway.
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Table 1.
Optimization of Reaction Conditionsa
SMe
SMe
OH
O
S
NH4I
+
+
SMe
1a
2a
3a
Yieldb (%)
Entry Halide (equiv.) Solvent(v/v)
Temp (oC)
100
2a
3a
1
2
3
4
5
6
7
8
9
NH4I (2 eq)
NH4I (2 eq)
NH4I (2 eq)
NH4I (2 eq)
NH4I (2 eq)
NH4I (3 eq)
NH4I (1 eq)
NH4I (2 eq)
NH4I (2 eq)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
19
<5
110
21
72
84
73
82
67
56
<5
<5
<5
<5
15
<5
13
12
69
120
130
140
130
130
DMSO/H2O (20:1) 130
DMSO/H2O (2:1) 130
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19c
20d
NH4I (1 eq)
NH4I (3 eq)
NH4I (2 eq)
NH4I (2 eq)
NH4I (2 eq)
Et4NI (2 eq)
NH4Br (2 eq)
HI (2 eq)
DMSO/H2O (2:1) 130
DMSO/H2O (2:1) 130
DMSO/H2O (1:1) 130
DMSO/H2O (1:1) 120
DMSO/H2O (1:2) 130
DMSO/H2O (1:1) 130
DMSO/H2O (1:1) 130
DMSO/H2O (1:1) 130
DMSO/H2O (1:1) 130
DMSO/H2O (1:1) 130
DMSO/H2O (1:1) 130
<5
<5
<5
<5
<5
0
65
72
87
48
35
<5
<5
32
53
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0
<5
<5
I2 (1 eq)
NH4I (2 eq)
NH4I (2 eq)
trace trace
trace trace
a Reaction conditions: alkene 1a (1.0 mmol), halide, solvent(v/v) (3.0 mL), 24h; Isolated
b
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yield. cBHT (1.5 mmol); dTEMPO (1.5 mmol).
With the optimized conditions in hand, the generality of this bis-sulfenylation reaction
was investigated. As shown in Scheme 2, allylbenzene derivatives with different substituents
on the phenyl ring, including electron-withdrawing and electron-donating groups, were
successfully converted to the corresponding bis-sulfenylation products 2a−m in moderate to
good yields. The addition of substituents at different positions on the aromatic ring of the
allylbenzenes had no significant effect on the yield. The reaction tolerated a range of
substituents including: -Me, -OMe, -F, -Cl, -CF3, -CN and -SMe. It is noteworthy that
2-allylnaphthalene gave product 2l in 83% yield under the standard reaction condition. It is
important to note that substrates bearing two electron-donating groups such as a
3,4-dimethoxy group also proceeded smoothly to afford the target product 2m in 43% yield.
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Furthermore, the optimized conditions are equally effective for other unactivated alkenes
(such as but-3-en-1-ylbenzene), to afford the bis-sulfenylation product 2n in good yields.
Unfortunately, the reaction with styrene, failed under the current reaction conditions (Scheme
2, 2o). The yield of the bis-sulfenylation products was slightly lower because there is always
accompanied by the hydroxysulfenylation product 3 (Scheme 3).
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Scheme 2.
Substrate scope for bis-sulfenylation reaction of alkenes a, b
DMSO
130 oC, 24 h
NH4I,
( )n
2
( )n
R
MeS
SMe
n = 1, 2
R
1
SMe
SMe
SMe
SMe
SMe
SMe
Me
SMe
2a
, 84%
2c
, 73%
Me
2b
, 71%
SMe
SMe
SMe
SMe
OMe
SMe
, 81%
Me
Cl
MeO
F3C
2d
, 75%
2e
2f
, 78%
SMe
SMe
SMe
SMe
SMe
SMe
SMe
SMe
SMe
F
2i
, 62%
SMe
2g
2j
2h
, 73%
, 86%
SMe
SMe
MeS
NC
, 54%
2k
, 65%
2l
, 83%
MeO
MeO
SMe
SMe
SMe
SMe
SMe
SMe
2o
2n,
56%
2m
, 43%
, < 5%
o
a Reaction conditions: alkene 1 (1.0 mmol), NH4I (2.0 mmol) in DMSO (3.0 mL) at 130 C
for 24 h; b Isolated yield.
To further explore the application of our approach, we turned our attention to the NH4I-promoted
and H2O-controlled hydroxysulfenylation of inactivated alkenes (Scheme 3). First, the various
allylbenzene derivatives underwent hydroxysulfenylation under the standard conditions: NH4I (2.0
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equiv), DMSO (1.5 mL), H2O (1.5 mL) and allylbenzene (1.0 mmol) at 130 °C for 24 h, which
provided products 3a in 87% yield (Table 1, entry 12). Similar to the bis-sulfenylation reaction, by
varying the R substituents of allylbenzene derivatives 1, it was observed that both
electron-withdrawing and electron-donating substituents could be introduced to afford the
hydroxysulfenylation products in moderate to good yields. The results indicated that the steric
hindrance of allylbenzenes had no obvious influence on the efficiency of the desired transformation
(Scheme 2, 3b and 3f), while electronic effects reduced the yields of 3 slightly (Scheme 2, 3h and
3i). It is noteworthy that 5-allyl-2-methoxyphenol also reacted smoothly with DMSO and H2O to
afford 3k in 65% yield. As the phenolic hydroxyl group can quench the radical, the yield could be
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improved
by
prolonging
the
reaction
time.
Interestingly,
the
use
of
1-allyl-2,3,4,5,6-pentafluorobenzene resulted in the formation of the corresponding β-hydroxysulfide
product 3l in moderate yield. Furthermore, the hydroxysulfenylation of but-3-en-1-ylbenzene with
DMSO under the optimized conditions gave 3m in 89% yield. Various substituted alkyl alkenes were
found to be compatible under the optimized condition. The terminal alkenes 1-octenes successfully
completed the hydroxysulfenylation reaction and gave the design product 3n in 67% yields. When
deuterated-DMSO was used as the reaction solvent and reagent, deuterium-labeled
hydroxysulfenylation product 3o were isolated in 65% yield, respectively.
Scheme 3. Substrate scope for the hydroxysulfenylation reactiona,b
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NH4I
OH
R
DMSO, H2O
SMe
R
1
3
7
8
9
Me
SMe
SMe
SMe
OH
OH
Me
OH
3c
, 83%
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3a
, 87%
3b
, 85%
SMe
SMe
MeO
SMe
OH
, 84%
OH
, 88%
OH
Me
Cl
OMe
3f
, 86%
3e
3d
SMe
SMe
SMe
SMe
OH
, 81%
OH
OH
F
F3C
F
3g
3h
3i
, 75%
, 73%
F
F
HO
OH
SMe
SMe
OH
OH
MeO
F
F
3j
, 86%
3k
, 65%
SMe
3l
, 52%
OH
C6H13
OH
SMe
OH
SCD3
d
3o,
65%
3m,
3n
89%
, 67%
a Reaction conditions: alkene 1 (1.0 mmol), NH4I (2.0 mmol) and H2O (1.5 mL) in DMSO
(1.5 mL) at 130 C for 24 h; Isolated yield; Detected by H-NMR; DMSO-d6 was used
o
b
c
1
d
instead of DMSO.
To continue our investigation of the reaction scope, we explored various 2-allylphenol substrates
for this process under the optimized reaction conditions (Scheme 4). Compared with
hydroxysulfenylation
of
inactivated
alkenes
，
Synthesis
of
2-((methylthio)methyl)-2,3-dihydrobenzofuran by 2-hydroxylylylation of 2-allylphenol was
achieved.[18] In this oxidizing system, both the methoxy group and the aldehyde group are not
affected. The aldehyde group substituted 2-hydroxyallylbenzene can smoothly gave the target
product 2-((methylthio)methyl)-2,3-dihydrobenzofuran-7-carbaldehyde 4b and 4d in good yields. It
is important to note that substrates bearing electron-donating group such as phenolic hydroxy group
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and allyl group also proceeded smoothly to afford the target product 4e in 72% yield. It is interesting
to note that 2-allyl-6-(2H-benzo[d][1,2,3]triazol-2-yl)-4-methylphenol gave product 4f in 81% yield
under the standard reaction condition.
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Scheme 4 Synthesis of dihydrobenzofurans from alkenes a, b
SMe
O
R
NH4I
130 o
R
+
S
OH
O
H3C
CH3
C
1
4
SMe
SMe
SMe
O
O
O
OMe
O
H
4a
, 92%
4b
, 85%
4c
, 89%
CH3
O
OH
N
N
H
N
SMe
O
SMe
O
O
OMe
4d
4f
, 81%
4e
, 72%
, 86%
SMe
a Reaction conditions: alkene 1 (1.0 mmol), NH4I (2.0 mmol) in DMSO (1.5 mL) at 130 C
o
for 18 h; b Isolated yield.
To gain mechanistic insights, isotopic labelling experiment using H2O18 were conducted to verify
the oxygen atom of the hydroxysulfenylation products. These results indicate that water acts as a
hydroxy donor in this transformation (Scheme 5a). Under N2 condition, the hydroxysulfenylation
product 3a was obtained in 83% yield (Scheme 5b). The result indicated that the formation of a
thiiranium ion intermediate could be the dominant pathway.
Scheme 5. Control experiments.
NH4I, H2O18
SMe
(a)
(b)
DMSO, 130 oC, 24h
18OH
3a-1
, 76%
NH4I, H2O, N2
SMe
DMSO, 130 oC, 24h
OH
3a
, 83%
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On the basis of our findings and previous literature, a possible mechanism is illustrated in
Scheme 6.[19] Initially, the iodine radical (I•)[20] and methanthiol (CH3SH)[21] are produced through a
series of transformations with NH4I and DMSO at high temperature. Iodine radicals can form
through a thermal decomposition process originating from NH4I, which can react with methanthiol to
liberate CH3S• radicals. The methylthiyl radical (CH3S•) B initiated by iodine radical selectively
adds to the terminal C=C double bond of 1 to form intermediate carbon radical C [22], which
undergoes further single-electron oxidation to afford a β-MeS-substituted carbocation D [23]. Then
the β-MeS-substituted carbocation D should immediately cyclize to a gives thiiranium ion E.
Subsequently, the nucleophilic attack of MeSH or H2O on the thiiranium ion E produces
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bis-sulfenylation products 2 or hydroxysulfenylation products 3 [2a-e, 3c]
.
Scheme 6. Proposed reaction mechanism.
130 oC
(CH3)2SO
(a)
(b)
MeSH
130 oC
NH4I
I
(c)
+
I
MeSH
+
HI
MeS
B
A
1
R
SMe
OH
SMe
SMe
H2O
R
R
2
3
C
SMe
R
MeSH
SET
-e
Me
S
SMe
R
R
E
D
In conclusion, we have demonstrated an efficient and attractive strategy for synthesis of valuable
bis-methylsulfane and β-hydroxysulfides through an NH4I-promoted and H2O-controlled
intermolecular bis-sulfenylation and hydroxysulfenylation of terminal alkenes. The method
complements existing approaches involving methylthiyl radical allylic C−H activation. The water
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played a critical role in this reaction. This reaction chemo- and regioselectively afforded the
bis-sulfenylation and hydroxysulfenylation products by varying the proportion of water. This unique
bis-sulfenylation and hydroxysulfenylation procedure used readily available, stable and odorless
DMSO as a thioetherification reagent, and has potential applications in modern organic synthesis
chemistry and pharmaceutical chemistry.
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EXPERIMENTAL SECTION
General Information: Unless otherwise noted, all commercial materials and solvents were used
without further purification and all the reactions were carried out in a Schlenk tube equipped with
1
13
magnetic stir bar. H NMR spectra were recorded in CDCl3 at 400 MHz (or 600 MHz) and C {1H}
NMR NMR spectra were recorded in CDCl3 at 100 MHz (or 150 MHz) respectively, 1H and 13C {1H}
NMR NMR were referenced to CDCl3 at δ 7.26 and 77.0 respectively. GC–MS was obtained using
electron ionization (Agilent Technologies 7890A/5975C). HRMS spectra were acquired using an
Agilent 6210 ESI/TOF mass spectrometer and MAT 95XP (Double-focusing Magnetic Sector
Analyzer), Thermo (EI, 70eV). TLC was performed using commercially prepared 100-400 mesh
silica gel plates (GF254), and visualization was effected at 254 nm. All the other chemicals were
purchased from Aldrich Chemicals. Commercial reagents were used without further purification.
Typical procedure for synthesis of 1-(2,3-bis(methylthio)propyl)benzene derivatives: A mixture
of allylbenzene (1 mmol), NH4I (2 mmol), DMSO (2 mL) was added successively in a 20 mL
o
Schlenk tube. The Schlenk tube was then immersed in an oil bath at 130 C stirring for 24 h. After
cooling down to room temperature, the solution was filtered through a small amount of silica gel.
Then the residue was concentrated in vacuo and the crude was purified by flash chromatography
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with n-hexane/ethyl acetate (10/1, v/v) to afford the (3-phenylpropane-1,2-diyl)bis(methylsulfane) as
a pale-yellow oil in 84% yield.
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Typical procedure for synthesis of 1-(methylthio)-3-phenylpropan-2-ol derivatives: A mixture
of allylbenzene (1 mmol), NH4I (2 mmol), DMSO (1.5 mL) and H2O (1.5 mL) was added
successively in a 20 mL Schlenk tube. The Schlenk tube was then immersed in an oil bath at 130 oC
stirring for 24 h. After cooling down to room temperature, the solution was filtered through a small
amount of silica gel. Then the residue was concentrated in vacuo and the crude was purified by flash
chromatography
with
n-hexane/ethyl
acetate
(8/1,
v/v)
to
afford
the
1-(methylthio)-3-phenylpropan-2-ol as a pale-yellow oil in 87% yield.
1-(2,3-bis(methylthio)propyl)benzene (2a): Pale-yellow liquid (178 mg, 84% yield), 1H NMR (400
MHz, CDCl3) δ 7.21 – 7.17 (m, 2H), 7.13 (dd, J = 7.5, 3.8 Hz, 3H), 3.03 (dd, J = 13.6, 5.8 Hz, 1H),
2.88 – 2.80 (m, 1H), 2.71 (ddd, J = 18.6, 13.5, 6.4 Hz, 2H), 2.57 (dd, J = 13.3, 7.6 Hz, 1H), 2.02 (s,
13
3H), 1.95 (s, 3H); C {1H} NMR NMR (100 MHz, CDCl3) δ 138.7, 129.1 (2C), 128.1 (2C), 126.2,
48.0, 39.4, 38.8, 16.2, 13.7. GC-MS (EI, 70 eV) m/z: 212, 164, 151, 121; HRMS (EI) m/z: [M]+
Calcd for C11H16S2 212.0688; Found, 212.0687.
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1-(2,3-bis(methylthio)propyl)-2-methylbenzene (2b): Pale-yellow liquid (160 mg, 71% yield), H
NMR (600 MHz, CDCl3) δ 7.20-7.18 (m, 1H), 7.16-7.14 (m, 3H), 3.17 (dd, J = 14.1, 6.3 Hz, 1H),
2.98 – 2.90 (m, 1H), 2.86 – 2.76 (m, 2H), 2.72 (dd, J = 13.3, 7.4 Hz, 1H), 2.36 (s, 3H), 2.14 (s, 3H),
2.05 (s, 3H); 13C {1H} NMR NMR (150 MHz, CDCl3) δ 137.4, 136.2, 130.4, 130.2, 126.6, 125.8,
47.4, 39.6, 37.4, 19.6, 16.6, 14.0. GC-MS (EI, 70 eV) m/z: 226, 178, 165, 121; HRMS (EI) m/z:
[M]+ Calcd for C12H18S2 226.0844; Found, 226.0843.
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1-(2,3-bis(methylthio)propyl)-3-methylbenzene (2c): Pale-yellow liquid(165 mg, 73% yield), H
NMR (600 MHz, CDCl3) δ 7.22 – 7.16 (m, 1H), 7.08 – 6.96 (m, 3H), 3.08 (dd, J = 13.8, 6.2 Hz, 1H),
2.97 – 2.90 (m, 1H), 2.84 – 2.74 (m, 2H), 2.68 (dd, J = 13.3, 7.5 Hz, 1H), 2.34 (s, 3H), 2.14 (s, 3H),
2.07 (s, 3H); 13C {1H} NMR NMR (150 MHz, CDCl3) δ 138.9, 137.9, 130.0, 128.2, 127.2, 126.3,
48.2, 39.6, 39.0, 21.4, 16.4, 13.9. GC-MS (EI, 70 eV) m/z: 226, 178, 165, 131, 121; HRMS (EI) m/z:
[M]+ Calcd for C12H18S2 226.0844; Found, 226.0846.
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1-(2,3-bis(methylthio)propyl)-4-methylbenzene (2d): Pale-yellow liquid (170 mg, 75% yield), H
NMR (600 MHz, CDCl3) δ 7.13-7.10 (m, 4H), 3.08 (dd, J = 13.9, 6.1 Hz, 1H), 2.95 – 2.89 (m, 1H),
2.84 – 2.77 (m, 2H), 2.67 (dd, J = 13.3, 7.7 Hz, 1H), 2.32 (s, 3H), 2.13 (s, 3H), 2.06 (s, 3H); 13C {1H}
NMR NMR (150 MHz, CDCl3) δ 136.0, 135.8 (2C), 129.2 (2C), 129.0, 48.3, 39.1, 39.0, 21.1, 16.4,
13.9. GC-MS (EI, 70 eV) m/z: 226, 178, 165, 121; HRMS (EI) m/z: [M]+ Calcd for C12H18S2
226.0844; Found, 226.0843.
1-(2,3-bis(methylthio)propyl)-2-methoxybenzene (2e): Pale-yellow liquid (189 mg, 78% yield),
1H NMR (600 MHz, CDCl3) δ 7.22 (td, J = 8.0, 1.7 Hz, 2H), 6.85 (d, J = 8.1 Hz, 2H), 3.82 (s, 3H),
3.11 (dt, J = 9.4, 6.8 Hz, 2H), 2.87 (td, J = 9.7, 5.0 Hz, 1H), 2.80 – 2.74 (m, 1H), 2.74 – 2.66 (m,
1H), 2.12 (s, 3H), 2.07 (s, 3H); 13C {1H} NMR NMR (150 MHz, CDCl3) δ 157.5, 131.2, 127.8, 127.4,
120.3, 110.2, 55.2, 46.3, 39.3, 35.1, 16.3, 13.6. GC-MS (EI, 70 eV) m/z: 242, 194, 181, 147. HRMS
(EI) m/z: [M]+ Calcd for C12H18OS2 242.0794; Found, 242.0792.
1-(2,3-bis(methylthio)propyl)-4-methoxybenzene (2f): Pale-yellow liquid (196 mg, 81% yield), 1H
NMR (600 MHz, CDCl3) δ 7.19 – 7.10 (m, 2H), 6.87 – 6.80 (m, 2H), 3.79 (s, 3H), 3.06 (dd, J = 13.9,
6.0 Hz, 1H), 2.95 – 2.85 (m, 1H), 2.80 – 2.75 (m, 2H), 2.66 (dd, J = 13.2, 7.7 Hz, 1H), 2.13 (s, 3H),
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2.06 (s, 3H); 13C {1H} NMR NMR (150 MHz, CDCl3) δ 158.2, 130.9, 130.6 (2C), 113.7 (2C), 55.2,
48.4, 38.9, 38.6, 16.4, 14.0. GC-MS (EI, 70 eV) m/z: 242, 194, 181, 147. HRMS (EI) m/z: [M]+
Calcd for C12H18OS2 242.0794; Found, 242.0792.
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(3-(3-chlorophenyl)propane-1,2-diyl)bis(methylsulfane) (2g): Pale-yellow liquid (180 mg, 73%
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yield), H NMR (400 MHz, CDCl3) δ 7.27 – 7.20 (m, 3H), 7.13 (d, J = 6.6 Hz, 1H), 3.13 (dd, J =
13.8, 5.5 Hz, 1H), 2.90 (ddd, J = 10.6, 7.9, 5.3 Hz, 1H), 2.79 (dt, J = 11.5, 5.0 Hz, 2H), 2.65 (dd, J =
13.3, 8.0 Hz, 1H), 2.14 (s, 3H), 2.06 (s, 3H); 13C {1H} NMR NMR (100 MHz, CDCl3) δ 141.0, 134.1,
129.5, 129.4, 127.6, 126.7, 48.0, 39.1 (2C), 16.4, 14.0. GC-MS (EI, 70 eV) m/z: 246, 210, 163, 150,
137, 121. HRMS (EI) m/z: [M]+ Calcd for C11H15ClS2 246.0298; Found, 246.0297.
1
1-(2,3-bis(methylthio)propyl)-4-fluorobenzene (2h): Pale-yellow liquid (198 mg, 86% yield), H
NMR (600 MHz, CDCl3) δ 7.23 – 7.16 (m, 2H), 7.04 – 6.95 (m, 2H), 3.11 (dd, J = 14.0, 5.6 Hz, 1H),
2.89 (tt, J = 7.9, 5.4 Hz, 1H), 2.78 (dd, J = 13.3, 5.2 Hz, 2H), 2.66 – 2.58 (m, 1H), 2.14 (s, 3H), 2.06
13
(s, 3H); C {1H} NMR NMR (150 MHz, CDCl3) δ 161.6 (d, JC-F = 243.0 Hz, 1C), 134.6 (d, JC-F
=
3.15 Hz, 1C), 130.7 (d, JC-F = 7.8 Hz, 2C), 115.1 (d, JC-F = 21.0 Hz, 2C), 48.3, 39.0, 38.6, 16.4, 14.0.
GC-MS (EI, 70 eV) m/z: 230, 182, 169, 135, 121. HRMS (EI) m/z: [M]+ Calcd for C11H15FS2
230.0594; Found, 230.0592.
1-(2,3-bis(methylthio)propyl)-4-(trifluoromethyl)benzene (2i): Pale-yellow liquid (174 mg, 62%
yield), 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.7 Hz, 2H), 7.36 (d, J = 7.8 Hz, 2H), 3.23 (dd, J =
13.5, 4.5 Hz, 1H), 2.95 – 2.77 (m, 3H), 2.65 (dd, J = 12.6, 8.3 Hz, 1H), 2.15(d, J = 1.2 Hz, 3H), 2.06
(d, J = 1.2 Hz, 3H); 13C {1H} NMR NMR (100 MHz, CDCl3) δ 143.1, 129.7 (4C), 128.8 (d, JC-F
=
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32.1 Hz, 1C), 125.2 (q, JC-F = 3.8 Hz, 1C), 47.9, 39.2, 39.1, 16.4, 14.0. GC-MS (EI, 70 eV) m/z: 280,
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232, 219, 185, 121. HRMS (EI) m/z: [M]+ Calcd for C12H15F3S2 280.0562; Found, 280.0564.
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4-(2,3-bis(methylthio)propyl)benzonitrile (2j): Pale-yellow liquid (128 mg,54% yield), H NMR
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(600 MHz, CDCl3) δ 7.60 (d, J = 8.1 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 3.25 (dd, J = 13.8, 4.9 Hz,
1H), 2.89 (dt, J = 13.3, 4.3 Hz, 1H), 2.87 – 2.78 (m, 2H), 2.62 (dd, J = 13.3, 8.6 Hz, 1H), 2.15 (s,
13
3H), 2.05 (s, 3H); C {1H} NMR (150 MHz, CDCl3) δ 144.7, 132.1 (2C), 130.2 (2C), 118.9, 110.4,
47.7, 39.3, 39.2, 16.4, 14.0. GC-MS (EI, 70 eV) m/z: 237, 189, 176, 142, 121. HRMS (EI) m/z: [M]+
Calcd for C12H15NS2 237.0640; Found, 237.0642.
(3-(4-(methylthio)phenyl)propane-1,2-diyl)bis(methylsulfane) (2k): Pale-yellow liquid (168 mg,
1
65% yield), H NMR (600 MHz, CDCl3) δ 7.20 (d, J = 8.2 Hz, 2H), 7.16 (d, J = 8.2 Hz, 2H), 3.09
(dd, J = 13.9, 5.9 Hz, 1H), 2.90 (ddd, J = 13.3, 7.6, 5.8 Hz, 1H), 2.83 – 2.74 (m, 2H), 2.66 (dd, J =
13.3, 7.8 Hz, 1H), 2.47 (s, 3H), 2.14 (s, 3H), 2.06 (s, 3H); 13C {1H} NMR (150 MHz, CDCl3) δ 136.2,
135.9, 129.8 (2C), 126.8 (2C), 48.2, 38.99, 38.95, 16.4, 16.0, 14.0. GC-MS (EI, 70 eV) m/z: 258,
210, 163, 150, 121. HRMS (EI) m/z: [M]+ Calcd for C12H18S3, 258.0565; Found, 258.0564.
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1-(2,3-bis(methylthio)propyl)naphthalene (2l): Pale-yellow liquid (217 mg, 83% yield), H NMR
(400 MHz, CDCl3) δ 8.16 (d, J = 8.3 Hz, 1H), 7.87 (s, 1H), 7.76 (dt, J = 6.3, 3.3 Hz, 1H), 7.57 – 7.46
(m, 2H), 7.44 – 7.36 (m, 2H), 3.71 (q, J = 9.4 Hz, 1H), 3.19 – 3.07 (m, 2H), 2.88 (dd, J = 13.3, 4.5
Hz, 1H), 2.81 – 2.68 (m, 1H), 2.15 (s, 3H), 2.02 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) δ 135.1,
133.9, 131.9, 128.9, 127.9, 127.4, 126.0, 125.5, 125.3, 123.6, 47.4, 39.9, 37.4, 16.6, 13.9. GC-MS
(EI, 70 eV) m/z: 262, 214, 167, 153, 121. HRMS (EI) m/z: [M]+ Calcd for C15H18S2, 262.0844;
Found, 262.0845.
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4-(2,3-bis(methylthio)propyl)-1,2-dimethoxybenzene (2m): Pale-yellow liquid (117 mg, 43%
yield), 1H NMR (600 MHz, CDCl3) δ 6.84 – 6.73 (m, 3H), 3.87 (d, J = 10.0 Hz, 6H), 3.06 – 3.02 (m,
1H), 2.94 – 2.89 (m, 1H), 2.86 – 2.74 (m, 2H), 2.68 – 2.64 (m, 1H), 2.14 (s, 3H), 2.08 (s, 3H); 13C
{1H} NMR (150 MHz, CDCl3) δ 148.7, 147.7, 131.4, 121.4, 112.6, 111.1, 55.9, 55.9, 48.4, 39.2,
39.0, 16.5, 14.1. GC-MS (EI, 70 eV) m/z: 272, 224, 177, 151; GC-MS (EI, 70 eV) m/z: 226, 165,
117. HRMS (EI) m/z: [M]+ Calcd for C13H20O2S2, 272.0899; Found, 272.0897.
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1-(3,4-bis(methylthio)butyl)benzene (2n): Pale-yellow liquid (127 mg, 56% yield), H NMR (600
MHz, CDCl3) δ 7.28 (s, 2H), 7.21 (dd, J = 17.1, 5.0 Hz, 3H), 2.89-2.83 (m, 2H), 2.81 – 2.73 (m, 2H),
13
2.66 (d, J = 6.6 Hz, 2H), 2.22 – 2.12 (m, 1H), 2.09 (s, 3H), 2.07 (s, 3H); C {1H} NMR (150 MHz,
CDCl3) δ 141.6, 128.5 (2C), 128.4 (2C), 125.9, 45.4, 39.8, 34.1, 32.8, 16.1, 13.0. GC-MS (EI, 70 eV)
m/z: 226, 165, 117. HRMS (EI) m/z: [M]+ Calcd for C12H18S2, 226.0844; Found, 226.0848.
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1-(methylthio)-3-phenylpropan-2-ol (3a): Pale-yellow liquid(158 mg, 87% yield), H NMR (400
MHz, CDCl3) δ 7.32 – 7.28 (m, 2H), 7.24 – 7.21 (m, 3H), 3.93 – 3.92 (m, 1H), 2.84 (d, J = 6.3 Hz,
13
2H), 2.66 (dd, J = 13.6, 3.8 Hz, 1H), 2.59 (s, 1H), 2.50 (dd, J = 13.6, 8.5 Hz, 1H), 2.09 (s, 3H); C
{1H} NMR (100 MHz, CDCl3) δ 137.9, 129.3 (2C), 128.4 (2C), 126.5, 69.9, 42.4, 41.2, 15.6. GC-MS
(EI, 70 eV) m/z: 182, 164, 117, 91. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C10H14OSNa 205.
0658; Found 205.0658.
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1-(methylthio)-3-o-tolylpropan-2-ol (3b): Pale-yellow liquid(167 mg, 85% yield), H NMR (400
MHz, CDCl3) δ 7.16 (dp, J = 9.2, 5.2, 4.4 Hz, 4H), 3.96 – 3.92 (m, 1H), 2.86 (d, J = 6.5 Hz, 2H),
2.69 (dd, J = 13.6, 3.9 Hz, 1H), 2.59 – 2.49 (m, 2H), 2.34 (s, 3H), 2.10 (s, 3H); 13C {1H} NMR (100
MHz, CDCl3) δ 136.5, 136.2, 130.4, 130.0, 126.6, 125.9, 69.3, 41.5, 39.7, 19.6, 15.7. GC-MS (EI, 70
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eV) m/z: 196, 178, 131, 106, 91. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C11H16OSNa 219.0814;
Found 219.0802.
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1-(methylthio)-3-m-tolylpropan-2-ol (3c): Pale-yellow liquid(163 mg, 83% yield), H NMR (400
MHz, CDCl3) δ 7.20 (t, J = 7.7 Hz, 1H), 7.04 (t, J = 7.6 Hz, 3H), 3.96 – 3.89 (m, 1H), 2.81 (d, J =
6.4 Hz, 2H), 2.68 (dd, J = 13.6, 3.8 Hz, 1H), 2.58 – 2.46 (m, 2H), 2.34 (s, 3H), 2.11 (s, 3H); 13C {1H}
NMR (100 MHz, CDCl3) δ 138.1, 137.8, 130.1, 128.4, 127.3, 126.3, 67.0, 42.5, 41.3, 21.4, 15.6.
GC-MS (EI, 70 eV) m/z: 196, 178, 131, 106, 91. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C11H16OSNa 219.0814; Found 219.0812.
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1-(methylthio)-3-p-tolylpropan-2-ol (3d): Pale-yellow liquid(172 mg, 88% yield), H NMR (400
MHz, CDCl3) δ 7.11 (s, 4H), 3.94 – 3.88 (m, 1H), 2.80 (d, J = 6.4 Hz, 2H), 2.67 (dd, J = 13.6, 3.8
Hz, 1H), 2.58 – 2.44 (m, 2H), 2.32 (s, 3H), 2.09 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) δ 136.1,
134.8, 129.3 (2C), 129.3 (2C), 70.1, 42.1, 41.3, 21.1, 15.7. GC-MS (EI, 70 eV) m/z: 196, 178, 131,
106, 91. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C11H16OSNa 219.0814; Found 219.0815.
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1-(4-methoxyphenyl)-3-(methylthio)propan-2-ol (3e): Pale-yellow liquid(178 mg, 84% yield), H
NMR (400 MHz, CDCl3) δ 7.15 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.6 Hz, 2H), 3.88 (dq, J = 8.2, 4.7,
4.1 Hz, 1H), 3.79 (s, 3H), 2.79 (d, J = 6.3 Hz, 2H), 2.71 – 2.62 (m, 1H), 2.50 (dd, J = 13.7, 8.6 Hz,
2H), 2.10 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) δ 158.3, 130.3 (2C), 129.8, 113.9 (2C), 70.0,
55.2, 41.6, 41.2, 15.6. GC-MS (EI, 70 eV) m/z: 212, 194, 147, 121. HRMS (EI) m/z: [M]+ Calcd for
C11H16O2S, 212.0866; Found, 212.0864.
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1-(2-methoxyphenyl)-3-(methylthio)propan-2-ol (3f): Pale-yellow liquid(182 mg, 86% yield), H
NMR (400 MHz, CDCl3) δ 7.25 – 7.10 (m, 2H), 6.98 – 6.78 (m, 2H), 4.01 (d, J = 11.1 Hz, 1H), 3.82
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(s, 3H), 2.99 – 2.82 (m, 2H), 2.79 (s, 1H), 2.65 (dd, J = 13.6, 4.3 Hz, 1H), 2.54 (dd, J = 13.6, 8.0 Hz,
1H), 2.11 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) δ 157.5, 131.4, 128.0, 126.4, 120.7, 110.5, 69.5,
55.3, 41.4, 37.2, 15.8. GC-MS (EI, 70 eV) m/z: 212, 194, 147, 121. HRMS (EI) m/z: [M]+ Calcd for
C11H16O2S, 212.0866; Found, 212.0867.
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1-(3-chlorophenyl)-3-(methylthio)propan-2-ol (3g): Pale-yellow liquid(175 mg, 81% yield), H
NMR (400 MHz, CDCl3) δ 7.23 (d, J = 7.5 Hz, 3H), 7.16 – 7.09 (m, 1H), 3.92 (ddt, J = 12.4, 6.2, 3.9
Hz, 1H), 2.82 (d, J = 6.3 Hz, 2H), 2.73 – 2.58 (m, 2H), 2.50 (dd, J = 13.7, 8.7 Hz, 1H), 2.11 (s, 3H);
13C {1H} NMR (100 MHz, CDCl3) δ 140.1, 134.2, 129.7, 129.4, 127.6, 126.7, 69.5, 42.0, 41.4, 15.6.
GC-MS (EI, 70 eV) m/z: 216, 198, 151, 91. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for
C10H13ClOSNa 239.0268; Found 239.0268.
1-(4-fluorophenyl)-3-(methylthio)propan-2-ol (3h): Pale-yellow liquid(170 mg, 85% yield), 1H
NMR (600 MHz, CDCl3) δ 7.23 – 7.16 (m, 2H), 7.04 – 6.95 (m, 2H), 3.93 – 3.85 (m, 1H), 2.81 (d, J
= 6.3 Hz, 2H), 2.67 (dd, J = 13.7, 3.7 Hz, 1H), 2.56 (s, 1H), 2.49 (dd, J = 13.7, 8.7 Hz, 1H), 2.10 (s,
3H); 13C {1H} NMR (150 MHz, CDCl3) δ 161.7 (d, JC-F = 93 Hz, 1C), 133.6 (d, JC-F = 3.15 Hz, 1C),
130.8 (d, JC-F = 7.8 Hz, 2C), 115.3 (d, JC-F = 21 Hz, 2C), 69.7, 41.6, 41.3, 15.6. GC-MS (EI, 70 eV)
m/z: 200, 169, 109, 91. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C10H13FOSNa 223.0563; Found
223.0563.
1-(4-(trifluoromethyl)phenyl)-3-(methylthio)propan-2-ol (3i): Pale-yellow liquid(183 mg, 73%
yield), 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 3.95 (ddq, J
= 8.7, 5.8, 3.2 Hz, 1H), 2.90 (d, J = 6.6 Hz, 2H), 2.69 (dd, J = 13.7, 3.7 Hz, 1H), 2.65 – 2.56 (m, 1H),
2.51 (dd, J = 13.7, 8.8 Hz, 1H), 2.11 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) δ 142.2, 129.7 (4C),
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128.9 (d, JC-F = 32.2 Hz, 1C), 125.3 (q, JC-F = 3.7 Hz, 1C), 69.3, 42.2, 41.5, 15.5. GC-MS (EI, 70 eV)
m/z: 250, 232, 185, 159, 91. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C11H13F3OSNa 273.0531;
Found 273.0533.
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1-(methylthio)-3-(naphthalen-4-yl)propan-2-ol (3j): Pale-yellow liquid (200 mg, 86% yield), H
NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.3 Hz, 1H), 7.92 – 7.85 (m, 1H), 7.77 (d, J = 7.7 Hz, 1H),
7.62 – 7.48 (m, 2H), 7.47 – 7.37 (m, 2H), 4.21 – 4.02 (m, 1H), 3.38 (dd, J = 13.9, 5.5 Hz, 1H), 3.29
(dd, J = 14.0, 7.4 Hz, 1H), 2.73 (dd, J = 13.6, 4.3 Hz, 1H), 2.68 – 2.49 (m, 2H), 2.10 (s, 3H); 13C
{1H} NMR (100 MHz, CDCl3) δ 134.1, 133.9, 132.1, 128.8, 127.6, 127.4, 126.0, 125.6, 125.4, 123.7,
69.5, 41.6, 39.6, 15.8. GC-MS (EI, 70 eV) m/z: 232, 214, 167, 142. HRMS (EI) m/z: [M]+ Calcd for
C14H16OS, 232.0916; Found, 232.0915.
5-(2-hydroxy-3-(methylthio)propyl)-2-methoxyphenol (3k): Pale-yellow liquid (148 mg, 65%
yield), 1H NMR (600 MHz, CDCl3) δ 6.88 – 6.81 (m, 1H), 6.74 (d, J = 1.8 Hz, 1H), 6.70 (dd, J = 8.0,
1.8 Hz, 1H), 5.71 (s, 1H), 3.92 – 3.87 (m, 1H), 3.86 (s, 3H), 2.77 (d, J = 6.0 Hz, 2H), 2.67 (dd, J =
13.6, 3.9 Hz, 1H), 2.62 (s, 1H), 2.50 (dd, J = 13.6, 8.5 Hz, 1H), 2.10 (s, 3H); 13C {1H} NMR (150
MHz, CDCl3) δ 146.4, 144.2, 129.6, 121.9, 114.4, 111.9, 70.1, 55.8, 42.0, 41.1, 15.6. GC-MS (EI, 70
eV) m/z: 228, 210, 163, 137. HRMS (EI) m/z: [M]+ Calcd for C11H16O3S, 228.0815; found,
228.0813.
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1-(methylthio)-3-(perfluorophenyl)propan-2-ol (3l): Pale-yellow liquid (141 mg, 52% yield), H
NMR (600 MHz, CDCl3) δ 3.99 – 3.86 (m, 1H), 2.92 (d, J = 6.5 Hz, 2H), 2.78 – 2.68 (m, 2H), 2.55
(dd, J = 13.8, 8.8 Hz, 1H), 2.13 (s, 3H); 13C {1H} NMR (150 MHz, CDCl3) δ 146.3-144.5 (m, 2C),
140.9-139.0 (m, 1C), 138.4-138.1 (m, 2C), 111.5 (dd, J = 20.6, 16.7 Hz, 1C), 67.7, 41.6, 29.1, 15.5.
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GC-MS (EI, 70 eV) m/z: 272, 207, 154. HRMS (APCI-TOF) m/z: [M-H2O+H]+ Calcd for C10H8F5S
255.0261; Found 255.0261.
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1-(methylthio)-4-phenylbutan-2-ol (3m) :Pale-yellow liquid (174 mg, 89% yield), H NMR (600
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MHz, CDCl3) δ 7.29 (t, J = 7.6 Hz, 2H), 7.20 (dd, J = 16.6, 7.6 Hz, 3H), 3.75 – 3.64 (m, 1H), 2.90 –
2.81 (m, 1H), 2.76 – 2.67 (m, 2H), 2.60 (s, 1H), 2.48 (dd, J = 13.7, 9.2 Hz, 1H), 2.10 (s, 3H), 1.87 –
1.75 (m, 2H); 13C {1H} NMR (150 MHz, CDCl3) δ 141.8, 128.43 (2C), 128.42 (2C), 125.9, 67.7,
42.3, 37.8, 32.1, 15.5. GC-MS (EI, 70 eV) m/z: 196, 148, 137, 117. HRMS (EI) m/z: [M]+ Calcd for
C11H16OS, 196.0916; Found 196.0915.
1-(methylthio)octan-2-ol (3n), Pale-yellow liquid (118 mg, 67% yield), H NMR (500 MHz,
CDCl3) δ 3.64 (dd, J = 11.3, 4.5 Hz, 1H), 3.47 (dd, J = 11.3, 7.3 Hz, 1H), 2.72 – 2.58 (m, 1H), 2.21
(s, 1H), 2.01 (s, 3H), 1.55 – 1.37 (m, 4H), 1.27 (t, J = 14.4 Hz, 6H), 0.87 (t, J = 6.7 Hz, 3H); 13C {1H}
NMR (126 MHz, CDCl3) δ 62.6, 50.0, 31.7, 30.7, 29.1, 27.0, 22.6, 14.1, 11.7. HRMS (EI) m/z: [M]+
Calcd for C9H20OS, 176.1229; found 176.1226,
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1-((methyl-d3)thio)-3-phenylpropan-2-ol (3o): Pale-yellow liquid (120 mg, 65% yield), H NMR
(400 MHz, CDCl3) δ 7.34 – 7.27 (m, 2H), 7.23 (d, J = 7.2 Hz, 3H), 3.93 (s, 1H), 2.84 (d, J = 6.3 Hz,
2H), 2.67 (d, J = 13.1 Hz, 1H), 2.51 (dd, J = 13.7, 8.9 Hz, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ
137.9, 129.4, 128.5, 126.5, 70.01, 42.5 (2C), 41.1. GC-MS (EI, 70 eV) m/z: 185, 167, 117. HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for C10H11D3NaOS 208.0846; Found 208.0843.
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1-(methylthio)-3-phenylpropan-2-ol-18O (3a-1): Pale-yellow liquid (140 mg, 76% yield), H NMR
(400 MHz, CDCl3) 1H NMR (500 MHz, CDCl3) δ 7.37 – 7.31 (m, 2H), 7.29 – 7.24 (m, 3H), 4.03 –
3.89 (m, 1H), 2.88 (dd, J = 6.4, 2.9 Hz, 2H), 2.71 (d, J = 12.4 Hz, 1H), 2.59 (s, 1H), 2.54 (dd, J =
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13.5, 8.8 Hz, 1H), 2.13 (s, 3H); C {1H} NMR (125 MHz, CDCl3) δ 207.1, 137.9, 129.4 (2C),
128.5(2C), 126.5, 69.8, 42.45, 41.3, 15.6. GC-MS (EI, 70 eV) m/z: 184, 164, 117, 91. HRMS
(ESI-TOF) m/z: [M+Na]+ Calcd for C10H1418OSNa 207.0700; Found 207.0700.
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2,3-dihydro-2-((methylthio)methyl)benzofuran (4a): Pale-yellow liquid (166 mg, 92% yield), H
NMR (600 MHz, CDCl3) δ 7.19 (d, J = 7.3 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.87 (t, J = 7.4 Hz,
1H), 6.80 (d, J = 8.0 Hz, 1H), 4.97 (dq, J = 9.0, 6.6 Hz, 1H), 3.38 (dd, J = 15.6, 9.1 Hz, 1H), 3.08
(dd, J = 15.6, 6.9 Hz, 1H), 2.91 (dd, J = 13.7, 6.0 Hz, 1H), 2.79 (dd, J = 13.7, 6.6 Hz, 1H), 2.23 (s,
3H); C {1H} NMR (150 MHz, CDCl3) δ 159.1, 128.0, 126.2, 125.0, 120.5, 109.4, 82.0, 39.2, 34.9,
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16.4. HRMS (APCI-TOF) m/z: [M+H]+ calcd for C10H13OS, 181.0687; Found, 181.0681.
2-((methylthio)methyl)-2,3-dihydrobenzofuran-7-carbaldehyde (4b): Pale-yellow liquid(177 mg,
85% yield), 1H NMR (600 MHz, CDCl3) δ 10.18 (s, 1H), 7.56 (dd, J = 7.8, 0.8 Hz, 1H), 7.42 – 7.30
(m, 1H), 6.91 (t, J = 7.5 Hz, 1H), 5.14 (dtd, J = 9.2, 6.8, 5.3 Hz, 1H), 3.36 (dd, J = 15.9, 9.2 Hz, 1H),
3.09 (dd, J = 15.9, 6.8 Hz, 1H), 2.94 (dd, J = 13.9, 5.3 Hz, 1H), 2.81 (dd, J = 13.9, 6.9 Hz, 1H), 2.20
(s, 3H); 13C {1H} NMR (150 MHz, CDCl3) δ 188.6, 161.4, 130.9, 128.8, 127.0, 120.7, 119.4, 84.2,
38.9, 33.6, 16.4. HRMS (ESI-TOF) m/z: [M+Na]+: Calcd for C11H12O2SNa 231.0450; Found,
231.0450.
7-methoxy-2-((methylthio)methyl)-2,3-dihydrobenzofuran (4c), Pale-yellow liquid: 187 mg, 89%
yield), 1H NMR (400 MHz, CDCl3) δ 6.88 – 6.78 (m, 2H), 6.74 (dd, J = 6.8, 3.8 Hz, 1H), 5.08 – 4.92
(m, 1H), 3.86 (s, 3H), 3.37 (dd, J = 15.6, 9.0 Hz, 1H), 3.12 (dd, J = 15.6, 7.2 Hz, 1H), 2.97 (dd, J =
13.6, 4.8 Hz, 1H), 2.79 (dd, J = 13.6, 7.8 Hz, 1H), 2.19 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) δ
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147.5, 144.5, 127.4, 121.1, 117.2, 111.2, 82.5, 55.9, 38.9, 35.3, 16.3. HRMS (ESI-TOF) m/z:
[M+H]+ Calcd for C11H15O2S 211.0787; Found, 211.0789.
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7-methoxy-2-((methylthio)methyl)-2,3-dihydrobenzofuran-5-carbaldehyde (4d), Pale-yellow
liquid: (195 mg, 82% yield), 1H NMR (400 MHz, CDCl3) δ 9.77 (s, 1H), 7.30 (d, J = 13.6 Hz, 2H),
5.20 – 5.00 (m, 1H), 3.89 (d, J = 2.6 Hz, 3H), 3.41 (dd, J = 14.9, 10.0 Hz, 1H), 3.25 – 3.08 (m, 1H),
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3.01 – 2.88 (m, 1H), 2.81 (ddd, J = 13.7, 7.4, 2.3 Hz, 1H), 2.17 (d, J = 2.5 Hz, 3H); C {1H} NMR
(100 MHz, CDCl3) δ 190.3, 153.3, 144.8, 131.1, 127.84, 121.4, 111.2, 84.1, 55.9, 38.7, 34.2, 16.2.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C12H15O3S 239.0736; Found, 239.0735.
4-allyl-2-(2-((methylthio)methyl)-2,3-dihydrobenzofuran-5-yl)phenol (4e), Pale-yellow liquid:
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(237 mg, 76% yield), H NMR (500 MHz, CDCl3) δ 7.28 (s, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.15 –
7.00 (m, 2H), 6.91 (dd, J = 13.1, 8.2 Hz, 2H), 5.99 (ddt, J = 16.8, 10.0, 6.7 Hz, 1H), 5.14 – 5.07 (m,
2H), 5.07 – 5.02 (m, 1H), 3.44 (dd, J = 15.9, 9.1 Hz, 1H), 3.37 (d, J = 6.7 Hz, 2H), 3.15 (dd, J =
15.9, 7.0 Hz, 1H), 3.00 – 2.91 (m, 1H), 2.84 (dd, J = 13.7, 6.5 Hz, 1H), 2.26 (s, 3H); 13C {1H} NMR
(125 MHz, CDCl3) δ 159.1, 150.8, 137.7, 132.2, 130.3, 129.3, 129.0, 128.7, 128.0, 127.6, 125.9,
115.6, 115.5, 110.0, 82.5, 39.4, 39.2, 34.8, 16.4. HRMS (APCI-TOF) m/z: [M+H]+ calcd for:
C19H21O2S 313.1262; Found, 313.1252.
2-(5-methyl-2-((methylthio)methyl)-2,3-dihydrobenzofuran-7-yl)-2H-benzo[d][1,2,3]triazole (4f),:
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Pale-yellow liquid (252 mg, 81% yield), H NMR (600 MHz, CDCl3) δ 7.95 (dd, J = 6.6, 3.1 Hz,
2H), 7.71 (s, 1H), 7.46 – 7.35 (m, 2H), 7.09 (s, 1H), 5.30 – 5.16 (m, 1H), 3.47 (dd, J = 15.8, 9.1 Hz,
1H), 3.18 (dd, J = 15.8, 6.3 Hz, 1H), 2.96 (dd, J = 13.8, 4.8 Hz, 1H), 2.79 (dd, J = 13.8, 7.9 Hz, 1H),
2.37 (s, 3H), 2.17 (s, 3H); 13C {1H} NMR (150 MHz, CDCl3) δ 149.1, 144.7, 131.0, 129.8, 126.8 (2C)
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, 126.5, 123.8, 123.0, 118.3 (2C), 83.8, 38.6, 34.7, 20.6, 16.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd
for C17H18N3OS 312.1165, found 312.1159.
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Supporting Information
Copies of NMR spectra for all compounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
Leeyib268@126.com; wyuchemcl@126.com
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank the Foundation of the Department of Education of Guangdong Province
(2017KZDXM085, 2018KZDXM070 and 2017KSYS010), Science and Technology
Foundation of Jiangmen City (2017012) and Science Foundation for Young Teachers of
Wuyi University (2016zk03) and Chemical Industry Collaborative Innovation Center of
Yueshan Town 2017(368) for financial support.
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