Copper-catalyzed diastereoselective hydrothioetherification of oxa(aza)benzonorbornadienes

Article abstract of DOI:10.1039/d0ob00659a

A novel copper-catalyzed hydrothioetherification of oxa(aza)bicyclic alkenes with potassium thioacetate and aryl or alkyl iodides to synthesize unsymmetrical thioethers has been developed. Notably, the reaction with complete diastereoselectivity went through a syn-selective addition process to give exo-adducts. In addition, this protocol exhibited high efficiency and good functional group tolerance to afford the target thioethers in moderate to good yields. Based on the results of mechanistic investigations, a plausible mechanism was proposed.

Full text of DOI:10.1039/d0ob00659a

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DOI: 10.1039/D0OB00659A
ARTICLE
Copper-Catalyzed Diastereoselective Hydrothioetherification of
Oxa(aza)benzonorbornadienes
Qifu Lina,b, Yongqi Yaoa, Wen Yanga, Yun Tana, Shuqi Chena, Donghan Chena, and Dingqiao Yang*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A novel copper-catalyzed hydrothioetherification of oxa(aza)bicyclic alkenes with potassium thioacetate and aryl or alkyl
iodides to synthesize unsymmetrical thioethers has been developed. Notably, the reaction with complete
diastereoselectivity went through the syn-selective addition process to give the exo-adducts. In addition, this protocol
exhibited high efficiency and good functional group tolerance to afford the target thioethers in moderate to good yields.
Based on the results of mechanistic investigations, a plausible mechanism was proposed.
www.rsc.org/
good yields (56–97%) and excellent enantioselectivities (up to 98%
ee).9b Later in 2019, our group developed a transition-metal-free
hydrothioetherification of oxa(aza)bicyclic alkenes with thiols, the
Introduction
Oxa(aza)benzonorbornadienes with special structure are used as
multipurpose building blocks to synthesize the stereochemically
defined complex molecules.1 Previous studies reveal that the
reactions of oxa(aza)benzonorbornadienes with nucleophiles are
mainly divided into two types: ring opening and addition reaction.
Our group2 and many other excellent groups, such as Lautens’
group3, Tam’s group4, Fan’s group5, etc6, have done many works
about the reaction of oxa(aza)bicyclic alkenes with multifarious
nucleophiles to generate multiple stereocenters and construct
carbon-carbon and carbon-heteroatom bonds.
desired adducts were obtained in good to excellent yields (up to
99%).9c Obviously, we could find that in the reported
hydrothioetherification of oxa(aza)bicyclic alkenes, malodorous
thiophenols and thiols were used as sulfur source, or expensive
transition-metals were used as catalysts. However, the types of
mercaptans are limited and most thiophenols or thiols have
unpleasant odors, which impede their application. To enrich the
types of sulfur source, plenty of inorganic sulfides are successfully
used as easily available starting materials, using multicomponent
strategy for the synthesis of organosulfur compounds.7e,10
Thioethers are ubiquitous structural motifs found in
pharmaceuticals, biologically active natural products, food
ingredients and agro-chemicals.7 The formation of C–S bond has
received great attention, and numerous methods for the
construction of C–S bonds to synthesize thioethers have been
developed.8 However, there are few studies on the
hydrothioetherification of oxa(aza)benzonorbornadienes (See
Scheme 1)9. In 2013, our group established an iridium-catalyzed
asymmetric hydrothioetherification of azabicyclic alkenes with
thiophenols, but only a few examples of target adducts with
medium yields (6–88%) and low ee values (0%–9% ees) were
obtained.9a In 2016, Wang’s group also demonstrated an iridium-
catalyzed asymmetric addition reaction of oxabenzonorbornadienes
with thiophenols, the corresponding products were afforded in
Potassium thioacetate as an inorganic sulfide has been extensively
investigated for introducing sulfur atoms into organic molecules
due to its odorless smell, low price, and easy handling.11 Transition-
metal catalyzed cross-coupling reactions of aryl halides with KSAc
have emerged as the reliable and powerful strategy for C–S bonds
formation to introduce the thioacetate group12 or synthesize aryl
thioethers13. However, the study on the hydrothioetherification of
alkenes with KSAc and aryl halides has not been reported. Herein,
we report the first example of a copper-catalyzed multicomponent
one-pot reaction of oxa(aza)benzonorbornadienes with KSAc and
aryl or alkyl iodides to synthesize thioethers.
Previous works:
R1
[Ir(COD)Cl]2
S
6-88% yields
0-9% ees
Our work
S-BINAP
THF, 80 o
R
N
C
S
S
56-97% yields
14-98% ees
Wang's work
Ir(COD)2BF4
R
R
X
O
X
RSH
S-Xyl-Binap
THF, rt
X= O, NR1
a. Key Laboratory of Theoretical Chemistry of Environment, Ministry of Education,
School of Chemistry, South China Normal University, Guangzhou 510006, People’s
Republic of China. E-mail: yangdq@scnu.edu.cn.
H2O
80 oC, 12 h
71-99% yields
Our work
b. College of Marine Sciences, Beibu Gulf University, Qinzhou 535011, People’s
Republic of China.
This work:
S
R
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
cat. [Cu]
O
O
RI
KSAc
DMF
Scheme 1 Hydrothioetherification of Oxa(aza)bicyclic Alkenes.
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Organic & Biomolecular Chemistry
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ARTICLE
14
15
16
Cu(OTs)2
Cu(OAc)2
CuSO4·5H2O
Cu(acac)2
Cu(acac)2
Cu(acac)2
--
Cu(acac)2
Cu(acac)2
Cu(acac)2
--
--
--
--
--
--
--
--
--
--
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
48
48
130
18
65
43
84
66
58
0
0
0
77
Results and discussion
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130
DOI: 10.1039/D0OB00659A
48
24
24
24
48
24
24
24
130
130
130
130
130
130
130
130
Our initial efforts were focused on screening suitable reaction
conditions for the hydrothioetherification of oxabicyclic alkenes.
KSAc was selected as sulfur source, oxabenzonorbornadiene 1a and
4-iodoanisole 2a was selected as representative substrate and aryl
iodide, respectively. Various types of copper catalysts and ligands
were selected and screened in different solvents at different
reaction time and temperatures in order to find the optimal
reaction conditions (see Table 1). It was found that the
corresponding exo-adduct 3aa could be obtained in 64% yield in the
presence of CuI (20 mol %) as catalyst and 1,10- phen (20 mol %) as
ligand in 2 mL DMF at 140 oC for 48 h under air (entry 1).
Meanwhile, a small amount of bis(4-methoxyphenyl)sulfane 4 as
by-product was isolated from the reaction mixture. The control
17
18c
19d
20
21e
22f
23g
aReaction conditions: 1a (0.2 mmol, 1 equiv.), 2a (0.4 mmol, 2 equiv.), KSAc
(0.8 mmol, 4 equiv.), catalyst (20 mol%), ligand (20 mol%), solvent (2 mL),
under air. bIsolated yield of 3aa after chromatography. c2a (0.3 mmol, 1.5
equiv.), KSAc (0.6 mmol, 3 equiv.). dCu(acac)2 (10 mol%). eS (0.8 mmol, 4
equiv.) instead of KSAc. fK2S2O5 (0.8 mmol, 4 equiv.) instead of KSAc. gUnder a
N2 atmosphere.
With the optimized conditions in hand, the substrate scope of aryl
and alkyl iodides was investigated (see Table 2). Different aryl
iodides with electron-withdrawing or electron-donating groups
were transformed into the desired adducts in 0% to 84% yields.
Halogen substituents such as F, Cl and Br were all tolerated under
the optimized reaction conditions, but the target adduct 3aj was
obtained in lower yield than the others. It was found that aryl
bromide can also undergo transition-metal-catalyzed cross-coupling
with KSAC12a,13a, which may be the reason for its low yield. Notably,
when using 4-nitroiodobenzene or 4-cyanoiodobenzene as
substrate, the corresponding products 3am and 3an could not be
afforded, but gave bis(4-nitrophenyl)sulfane and 4,4'-
thiodibenzonitrile as the main products respectively. The strong
electron-withdrawing effect of nitro or cyano group may be the
reason why the reaction does not proceed normally. Moreover, it
was observed that steric hindrance seemed to have an effect on the
results. For example, 4-iodoanisole and 1-chloro-4-iodobenzene
gave the desired products in 84% and 83% yields, respectively,
while 75% and 72% yields were obtained in the case of 2-
iodoanisole and 1-chloro-2-iodobenzene as substrates. In addition,
it was observed that heterocyclic and alkyl iodides also worked in
this reaction system. The corresponding products 3ap, 3aq and 3ar
o
experiments that lowering the temperature to 130 C made little
effect on the yield of desired adduct, but lowered the temperature
o
to 120 C resulted in a decreased yield to 52% (entry 2–3). To our
surprise, it was proved to be more effective without ligand (entries
4–6). Among other solvents tested, DMSO, DMAc and para-xylene
(PX) also worked as solvents, but that gave lower yields than in DMF
(entries 7–9). It was observed that when 2,2'-bipyridine and TMEDA
were added as ligands or para-xylene was used as the solvent, the
amount of by-product 4 was greatly increased, which resulted in a
low yield of desired product. Then various types of copper catalysts
were investigated (entries 10–17). To our delight, Cu(acac)2 as the
best catalyst could increase the yield to 84% and reduce reaction
time to 24 h (entry 17). Reducing the amount of 2a and KSAc to 1.5
and 3 equivalents, respectively, proved to be less effective (entry
18). Moreover, decreasing the amount of Cu(acac)2 to 10 mol % or 0
mol % gave the worse results, producing 3aa in 58% and 0% yield,
respectively (entries 19–20). Notably, when using S or K2S2O5
instead of KSAc as the sulfur source, the desired product 3aa could
not be obtained (entries 21–22). In addition, it was found that this were obtained in moderate yields (55%–63%) when 2-
iodothiophene, 3-iodothiophene and 2-iodopyridine used as the
substrate, respectively. 1-Iodo-2-methylpropane worked better
than iodocyclohexane, gave the target products in 48% and 31%
yields, respectively.
reaction did not required an inert atmosphere and the yield of 3aa
was decreased to 77% when the reaction was performed under a N2
atmosphere (entry 23).
Table 1 Optimization for the Reaction Conditions.a
Table 2 Scope of Aryl and Alkyl Iodides.a
S
O
S
Cu(acac)2
R
OMe
O
KSAc
O
R
I
3aa
DMF, 24 h, 130 o
C
[Cu] cat.
R = aryl or alkyl
O
I
OMe
KSAc
S
1a
2a-2t
3aa-3at
1a
2a
b
3aa
3ab
3ac
3ah
, R = 4-OMe, 84% (66%)
, R = 3-Cl, 78%
R = 4-Cl, 83%
R = 4-Br, 61%
, R = 4-CF3, 63%
R = 4-ph, 65%
MeO
OMe
3ai
3aj
, R = H, 82%
,
4, by-product
S
S
, R = 4-CH3, 78%
, R = 2-OMe, 75%
, R = 3-OMe, 79%
,
O
R
3ad
3ae
3ak
3al
Entry
Catalyst
Ligand
Solvent
T
Temp Yieldb
(h)
48
48
48
48
48
48
48
48
48
48
48
48
48
. (oC)
140
130
120
130
130
130
130
130
130
130
130
130
130
(%)
64
68
52
trace
16
70
16
57
14
22
28
21
,
c
3af
3am
,
R = 4-F, 77%
, R = 4-NO2, N.R.
R = 4-CN, N.R.c
1
2
3
4
5
6
7
8
9
10
11
12
13
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuCl
CuCN
CuSCN
CuTC
1,10-Phen
1,10-Phen
1,10-Phen
2,2'-Bipyridine
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
DMAc
PX
3ag
3an
, R = 2-Cl, 72%
,
S
S
S
S
O
O
O
TMEDA
3ao
3ap
3aq
, 69%
S
, 63%
S
, 58%
S
--
--
--
--
--
--
--
--
N
O
O
O
3ar
3as
, 55%
, 31%
3at
, 48%
DMF
DMF
DMF
DMF
aReaction conditions: 1a (0.2 mmol), 2 (0.4 mmol), KSAc (0.8 mmol), Cu(acac)2 (20
mol%), DMF (2 mL), 130 oC, 24 h, under air. Isolated yield. bIsolated yield on a 1
mmol scale. cN.R., no reaction.
63
2 |
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Organic & Biomolecular Chemistry
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ARTICLE
R
Subsequently, a series of oxa(aza)bicyclic alkenes 1b−1k were
View Article Online
S
DOI: 10.1039/D0OB00659A
investigated to explore the scope of the substrates (see Table 3).
Oxabenzonorbornadienes with different substituents were
transformed into the desired products in moderate to good yields
O
R
OMe
OMe
3'
Cu(acac)2
KSAc
O
DMF, 24 h, 130 o
C
S
(57%–83%).
It
was
observed
that bromine-substituted
O
I
1l:
1m:
R = CH3
R = COCH3
OMe
oxabenzonorbornadiene 1f worked less effective and gave the
corresponding product 3fb in 57% yield, which may be due to the
fact that the aryl bromide can also undergo cross-coupling
reactions. Moreover, the desired products 3ib and 3jb could be
afforded in moderate yields (53% and 60%, respectively) by using
azabenzonorbornadienes 1i and 1j as substrates. The steric
hindrance formed by the substituent on nitrogen may be the reason
why the reactivity of azabenzonorbornadiene is lower than that of
oxabenzonorbornadiene. However, using norbornene as substrate
could not give the target product 3kb. This result indicated that the
oxygen or nitrogen atom on the oxa(aza)bicyclic alkenes might have
a certain effect on their reactivity in this protocol. To further
confirm the stereoscopic configuration of the corresponding
adducts, the X-ray single crystal diffraction analysis of 3cb was
performed. The result reveals that the phenylthio group of the
product stands at the exo orientation.
2a
R
3
3la 3la'
] / [
3ma 3ma'
] / [
[
[
] = 2 : 1
] = 1 : 2 68% yield in total
75% yield in total
Scheme 2 Scope of Unsymmetrical Oxabicyclic Alkenes.
In addition, the adduct 3aa can be easily transformed into other
important organosulfur compounds (see Scheme 3). Under the
oxidation of excess m-chloroperbenzoic acid (m-CPBA), 3aa was
oxidized to form sulfone 5 in 90% yield and the exo orientation of
the product had not been changed. Moreover, the adduct 3aa could
be directly functionalized to NH-sulfoximine 6 in 88% yield through
a one-pot reaction.
O
O
S
m-CPBA
CH2Cl2, rt
O
OMe
OMe
S
5
, 90%
NH
O
O
Table 3 Scope of Oxa(aza)bicyclic Alkenes.a
OMe
ammonium carbamate,
(diacetoxyiodo)benzene
S
3aa
O
R
R
C2H5OH, rt
S
6
, 88%, dr = 1.54 : 1
Cu(acac)2
X
X
I
KSAc
DMF, 24 h, 130 o
C
Scheme 3 Functionalization of Product 3aa.
R
R
1b-1k
2b
3bb-3kb
In order to gain insight into this reaction, some control experiments
and deuterium-labelling experiments were conducted (see Scheme
4). Due to the fact that bis(4-methoxyphenyl)sulfane 4 was isolated
from the reaction mixture when we purified the target adduct 3aa.
While we used bis(4-methoxyphenyl)sulfane as sulfur source for the
reaction, the expected adduct 3aa could not be obtained, indicating
that bis(4-methoxyphenyl)sulfane existed as the by-product during
the process (eq 1). Furthermore, when 2 equivalents of TEMPO or
BHT were added, the reactions were not completely suppressed;
the yields of 3aa decreased to 35% and 62%, respectively, implying
that the reaction might not involve a radical reaction process (eq 2–
3). Moreover, no deuterium incorporation in the desired product
was noted when using deuterated DMF as the solvent, indicating
that DMF did not act as the hydrogen source in this protocol (eq 4).
When D2O and DMF used as the mixed solvent, partially labelled
products were obtained and the deuteration ratio of the product
increased with the amount of D2O (eq 5–6). The observation
indicated that the water in the DMF or air should be the hydrogen
source for this hydrothioetherification reaction. In addition, to
explore the position where the hydrogen atom was introduced the
2D-NOESY spectra analysis of 3db (see Supporting Information) and
deuterium-labelling experiment (eq 7) was performed. The
observation that the exo hydrogen atom of the product 3db-D1 was
partially deuterated indicated that the hydrothioetherification of
oxa(aza)bicyclic alkenes was a syn-selective addition reaction.
S
MeO
MeO
S
O
O
3bb
3cb
, 83%
S
, 80%
CCDC 1970314
OMe
F
F
S
Br
Br
S
O
O
O
OMe
3db
3eb
3fb
, 77%
S
, 78%
S
, 57%
S
Ts
O
N
O
3gb
, 81%
S
3hb
3ib
, 73%
, 53%
Ts = p-toluenesulfonyl
Boc
S
N
b
3jb
3kb
, N.R.
, 60%
aReaction conditions: 1 (0.2 mmol), 2b (0.4 mmol), KSAc (0.8 mmol), Cu(acac)2 (20
mol%), DMF (2 mL), 130 oC, 24 h, under air. Isolated yield. bN.R., no reaction.
Moreover, unsymmetrical oxabenzonorbornadienes 1l and 1m
were chosen as substrates to investigate the regioselectivity of the
reaction under the optimized conditions (see Scheme 2). With the
methyl group on the bridgehead position of oxabicyclic alkene, the
adducts of 3la and 3la' were attained as 2 : 1 (mole ratio,
determined by 1H NMR spectroscopy) mixtures in a total yield of
75%. However, when acetyl group instead of methyl group on the
bridgehead, the products 3ma and 3ma' were obtained in the mole
ratio 1 : 2 and a total yield of 68%. The electronic effects of the
groups on the bridgehead of oxabenzonorbornadiene might be the
reason resulted in the opposite regioisomer ratios.
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Organic & Biomolecular Chemistry
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ARTICLE
a) Control experiments
CONCLUSIONS
View Article Online
DOI: 10.1039/D0OB00659A
standard conditions
1a
4
(1)
3aa
,
0%
0.2 mmol
0.4 mmol
In summary, we have demonstrated a novel copper-catalyzed
standard conditions
TEMPO (2 equiv.)
3aa
,
35%
62%
(2) 1a
2a
2a
KSAc
KSAc
complete
diastereoselective
hydrothioetherification
of
oxa(aza)bicyclic alkenes with potassium thioacetate and aryl or alkyl
iodides to afford the syn-selective adducts. This study provided a
valuable and efficient strategy to introduce arylthio or alkylthio
group to the carbon-carbon double bond via a copper-catalyzed C–S
reconstruction process. Moreover, this protocol exhibited high
efficiency and good functional group tolerance to afford the target
products in moderate to good yields. Further synthetic applications
and more detailed mechanism studies of this reaction are ongoing
in our laboratory.
standard conditions
BHT (2 equiv.)
(3)
1a
3aa
,
b) Deuterium-labelling experiments
20 mol % Cu(acac)2
S
D
O
(4) 1a
2a
2a
2a
KSAc
KSAc
KSAc
2 mL DMF-d7
130 oC, 24 h
OMe
OMe
OMe
3aa-D0
, 78%, (0% D)
S
20 mol % Cu(acac)2
O
(5)
(6)
1a
1a
2 mL DMF/0.2 mL D2O
130 oC, 24 h
D
3aa-D1
, 75%, (49% D)
S
20 mol % Cu(acac)2
O
2 mL DMF/0.4 mL D2O
130 oC, 24 h
EXPERIMENTAL SECTION
D
3aa-D2
, 70%, (68% D)
OMe
General Information
S
20 mol % Cu(acac)2
(7)
1d
2b
O
KSAc
Oxa(aza)benzonorbornadienes 1a-1m were prepared by the
2 mL DMF/0.4 mL D2O
130 oC, 24 h
D
literature procedures3a,6e,15
. Unless otherwise noted, all the
OMe
3db-D1
, 68%, (63% D)
reagents were purchased from commercial domestic chemical
companies such as Innochem, Alfa Acros, and Aladdin. Anhydrous
toluene, dimethoxyethane, and tetrahydrofuran were distilled from
Scheme 4 Mechanistic Investigations.
According to our above mechanistic investigations and related sodium benzophenone ketyl prior to use. Infrared spectra (IR) were
references14, a plausible mechanism is illustrated in Scheme 5. The obtained with thin film samples on a PerkinElmer Spectrum Two
first step of the catalytic cycle would be a copper-catalyzed spectrometer, and data are expressed in cm−1. 1H NMR, 13C NMR
substitution reaction of aryl or alkyl iodides with KSAc to afford the and 19F NMR spectra were recorded on Bruker-Avance 600 MHz
S-substituted thioacetate A. Then complex B is obtained through spectrometer. Chloroform-d was used as deuterated solvent.
the oxidative-insertion reaction. Possibly due to the conjugation of Spectral data are reported as follows: chemical shift (δ, ppm);
the aromatic ring, the substitution reaction of the aryl iodides and multiplicity (s-singlet, d-doublet, t-triplet, q-quadruplet, m-
the subsequent oxidative-insertion into the S-Ac bond proceed multiplet); coupling constants (J, Hz) and number of protons. 1H
more easily, resulting in an effect of the aryl iodides as substrates is NMR chemical shifts are reported in relative to internal
better than that of alkyl iodides. On one hand, complex B reacts tetramethylsilane (δ = 0.00), 13C NMR chemical shifts are reported
with aryl or alkyl iodides and undergoes reductive elimination to in relative to chloroform-d (δ = 77.16). High resolution mass spectra
generate the by-product. On the other hand, complex B combines (HRMS) (ion trap) were obtained from mass spectrometer (ESI) and
with oxabicyclic alkene 1a to give the intermediate C. Subsequently, MS were recorded using EI at 70 eV. Melting points were recorded
intermediate C transforms into complex E through a transition on an electrothermal digital melting point apparatus and were
structure D. Finally, protonation of the complex E by water provides uncorrected. Column chromatography was performed with silica gel
the syn-selective adduct 3, with the regeneration of the catalyst for (200-300 mesh) by using ethyl acetate/petroleum ether as eluent.
the next catalytic cycle.
Synthetic procedures
O
H
General procedure (I): the synthesis of products 3
SR
KSAc
RI
All
experiments
were
carried
out
under
air.
3
KI
[Cu]
Oxa(aza)benzonorbornadiene 1 (0.2 mmol, 1.0 equiv.), aryl or alkyl
iodide 2 (0.4 mmol, 2 equiv.), KSAc (91.2 mg, 0.8 mmol, 4 equiv.),
Cu(acac)2 (10.5 mg, 0.04 mmol, 20 mol %), and DMF (2 mL) were
added to a 10 mL round-bottomed flask. Then the mixture was
H2O
(A)
RSAc
[Cu]
Ac
Cull
SR
O
o
stirred at 130 C in oil bath for 24 h with TLC monitoring until the
(E)
complete consumption of 1. After cooling to the room temperature,
the reaction mixture was poured into the distilled water (20 mL)
and extracted three times with dichloromethane (3×10 mL). The
organic layers were combined, washed with brine, dried over
Na2SO4, and then concentrated in vacuo. The residue was purified
by silica gel column chromatography (using 5%~20% ethyl
acetate/petroleum ether as eluent) to afford the desired products 3.
Ac
Cull
SR
(B)
Ac
CullI
O
S
1a
R
RI
Ac
O
(D)
Cull
SR
S
R
R
by-product
(C)
General procedure (II): the synthesis of product 5
Scheme 5 Plausible Mechanism.
Compound 3aa (112.8 mg, 0.4 mmol, 1 equiv.), m-CPBA (281.2 mg,
1.6 mmol, 4 equiv.), and 10.0 mL dichloromethane were added to a
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ARTICLE
25 mL round-bottomed flask. Then the mixture was stirred at room 7.18 – 7.14 (m, 2H), 6.96 (td, J = 7.2, 1.2 Hz, 1H), 6.89 (dd, J = 7.8,
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DOI: 10.1039/D0OB00659A
temperature for 8 h with TLC monitoring until the complete 0.6 Hz, 1H), 5.45 (t, J = 3.0 Hz, 1H), 5.21 (s, 1H), 3.88 (s, 3H), 3.36 (dd,
consumption of 3aa. The reaction mixture was washed with J = 7.2, 6.0 Hz, 1H), 2.00 – 1.98 (m, 2H). 13C NMR (150 MHz, CDCl3) δ
aqueous Na2S2O3, and extracted with dichloromethane three times 158.0, 145.7, 144.0, 131.2, 128.2, 127.2, 126.9, 124.4, 121.2, 119.4,
(3×10 mL). The organic layers were combined, dried over Na2SO4, 119.3, 110.9, 83.3, 79.2, 55.9, 44.8, 35.8. HRMS calcd for C17H17O2S
and then concentrated under reduced pressure; the residue was [M+H]+: 285.0944. Found: 285.0952.
purified by gel column chromatography (using 50% ethyl
2-exo-((3-Methoxyphenyl)thio)-1,2,3,4-tetrahydro-1,4-
acetate/petroleum ether as eluent) to afford the product 5.
epoxynaphthalene (3ae)
General procedure (III): the synthesis of product 6
Following the general procedure (I), the product 3ae was obtained
Compound 3aa (142.1 mg, 0.5 mmol, 1 equiv.), ammonium as yellow oil (44.9 mg, 79% yield). IR (film) ν: 2930, 1586, 1476,
carbamate (78.1 mg, 1 mmol, 2 equiv.), (diacetoxyiodo)benzene 1283, 1246, 1040, 761, 629. 1H NMR (600 MHz, CDCl3) δ 7.25 – 7.24
(402.6 mg, 1.25 mmol, 2.5 equiv.) and 10 mL ethanol were added to (m, 3H), 7.20 – 7.16 (m, 2H), 6.97 (ddd, J = 2.4, 1.8, 1.2 Hz, 1H), 6.93
a 25 mL round-bottomed flask. Then the mixture was stirred at (t, J = 2.4 Hz, 1H), 6.77 (ddd, J = 3.6, 2.4, 0.6 Hz, 1H), 5.47 (d, J = 4.2
room temperature for 4 h with TLC monitoring until the complete Hz, 1H), 5.24 (s, 1H), 3.81 (s, 3H), 3.35 (dd, J = 7.8, 4.2 Hz, 1H), 2.03
consumption of 3aa. The solvent was removed under reduced – 1.96 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 160.1, 145.6, 143.8,
pressure; the residue was purified by gel column chromatography 137.9, 130.1, 127.4, 127.1, 121.7, 119.5, 119.4, 115.0, 112.3, 83.3,
(using 90% ethyl acetate/petroleum ether as eluent) to afford the 79.3, 55.4, 46.1, 35.7. HRMS calcd for C17H17O2S [M+H]+: 285.0944.
product 6.
Found: 285.0947.
2-exo-((4-Methoxyphenyl)thio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3aa)
2-exo-((4-Fluorophenyl)thio))-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3af)
Following the general procedure (I), the product 3aa was obtained Following the general procedure (I), the product 3af was obtained
as brown oil (47.7 mg, 84% yield). IR (film) ν: 2932, 1590, 1491, as yellow paste (41.9 mg, 77% yield). IR (film) ν: 2926, 1588, 1488,
1
1459, 1284, 1243, 1175, 1028, 984, 828, 758, 628. H NMR (600 1223, 983, 827, 758, 632. 1H NMR (600 MHz, CDCl3) δ 7.45 – 7.41 (m,
MHz, CDCl3) δ 7.45 – 7.42 (m, 2H), 7.21 (d, J = 6.6 Hz, 1H), 7.16 – 2H), 7.24 – 7.23 (m, 1H), 7.20 – 7.14 (m, 3H), 7.06 – 7.02 (m, 2H),
7.11 (m, 3H), 6.90 – 6.87 (m, 2H), 5.45 (t, J = 2.4 Hz, 1H), 5.18 (s, 1H), 5.46 (d, J = 4.2 Hz, 1H), 5.18 (s, 1H), 3.24 (dd, J = 7.8, 4.8 Hz, 1H),
3.81 (s, 3H), 3.18 (t, J = 6.0 Hz, 1H), 1.94 – 1.93 (m, 2H). 13C NMR 2.00 – 1.93 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 162.2 (d, JCF
=
(150 MHz, CDCl3) δ 159.5, 145.7, 143.9, 134.1, 127.2, 126.9, 126.2, 245.9 Hz), 145.6, 143.7, 133.3 (d, JCF = 8.0 Hz), 131.1 (d, JCF = 3.2 Hz),
119.5, 119.2, 114.9, 83.1, 79.3, 55.5, 48.3, 35.7. HRMS calcd for 127.4, 127.1, 119.5, 119.3, 116.4 (d, JCF = 21.8 Hz), 83.2, 79.3, 47.7,
C17H17O2S [M+H]+: 285.0944. Found: 285.0952.
35.8. 19F NMR (564 MHz, CDCl3) δ -114.5. HRMS calcd for C16H14FOS
[M+H]+: 273.0744. Found: 273.0752.
2-exo-(Phenylthio)-1,2,3,4-tetrahydro-1,4-epoxynaphthalene (3ab)
Following the general procedure (I), the product 3ab was obtained 2-exo-((2-Chlorophenyl)thio)-1,2,3,4-tetrahydro-1,4-
as yellow oil (41.6 mg, 82% yield). IR (film) ν: 2926, 1585, 1459, epoxynaphthalene (3ag)
1285, 984, 837, 740, 628. 1H NMR (600 MHz, CDCl3) δ 7.41 – 7.39 (m, Following the general procedure (I), the product 3ag was obtained
o
2H), 7.34 – 7.31 (m, 2H), 7.25 – 7.21 (m, 3H), 7.19 – 7.15 (m, 2H), as brown solid (41.5 mg, 72% yield). Mp = 78 – 79 C. IR (film) ν:
5.47 (d, J = 4.2 Hz, 1H), 5.22 (s, 1H), 3.34 (dd, J = 7.2, 4.2 Hz, 1H), 2926, 1452, 1210, 1035, 986, 838, 754, 629. 1H NMR (600 MHz,
2.03 – 1.96 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 145.6, 143.8, 136.5, CDCl3) δ 7.41 (dd, J = 7.8, 1.2 Hz, 1H), 7.35 (dd, J = 8.4, 1.8 Hz, 1H),
129.9, 129.2, 127.4, 127.1, 126.6, 119.5, 119.3, 83.3, 79.3, 46.3, 7.29 – 7.25 (m, 3H), 7.21 – 7.16 (m, 3H), 5.50 (d, J = 4.2 Hz, 1H), 5.24
35.8. HRMS calcd for C16H15OS [M+H]+: 255.0838. Found: 255.0848.
(s, 1H), 3.37 (dd, J = 7.2, 5.4 Hz, 1H), 2.07 – 2.05 (m, 2H). 13C NMR
(150 MHz, CDCl3) δ 145.6, 143.7, 136.1, 134.1, 130.1, 129.5, 127.5,
127.4, 127.2, 127.2, 119.5, 119.4, 83.2, 79.3, 45.1, 35.8. HRMS calcd
for C16H14ClOS [M+H]+: 289.0448. Found: 289.0455.
2-exo-(p-Tolylthio)-1,2,3,4-tetrahydro-1,4-epoxynaphthalene (3ac)
Following the general procedure (I), the product 3ac was obtained
as brown oil (41.8 mg, 78% yield). IR (film) ν: 2923, 1492, 1458, 985,
804, 760, 628. 1H NMR (600 MHz, CDCl3) δ 7.34 – 7.32 (m, 2H), 7.24 2-exo-((3-Chlorophenyl)thio)-1,2,3,4-tetrahydro-1,4-
– 7.22 (m, 1H), 7.20 – 7.19 (m, 1H), 7.18 – 7.13 (m, 4H), 5.46 (d, J = epoxynaphthalene (3ah)
4.2 Hz, 1H), 5.20 (s, 1H), 3.28 (dd, J = 7.2, 4.2 Hz, 1H), 2.34 (s, 3H), Following the general procedure (I), the product 3ah was obtained
1.98 – 1.96 (m, 2H). 13C NMR (150 MHz, CDCl3) δ 145.7, 143.9, 136.9, as brown oil (44.9 mg, 78% yield). IR (film) ν: 2933, 1576, 1461,
132.6, 130.9, 130.0, 127.3, 127.0, 119.5, 119.3, 83.2, 79.3, 47.0, 1294, 1159, 1082, 939, 759, 676. 1H NMR (600 MHz, CDCl3) δ 7.34 –
35.7, 21.2. HRMS calcd for C17H17OS [M+H]+: 269.0995. Found: 7.33 (m, 1H), 7.28 – 7.23 (m, 4H), 7.21 – 7.18 (m, 3H), 5.48 (d, J =
269.1002.
4.8 Hz, 1H), 5.22 (s, 1H), 3.33 (dd, J = 7.8, 4.2 Hz, 1H), 2.05 – 1.96 (m,
2H). 13C NMR (150 MHz, CDCl3) δ 145.5, 143.6, 138.9, 135.0, 130.2,
128.8, 127.5, 127.3, 127.2, 126.5, 119.5, 119.4, 83.2, 79.3, 46.0,
35.8. HRMS calcd for C16H14ClOS [M+H]+: 289.0448. Found:
289.0456.
2-exo-((2-Methoxyphenyl)thio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3ad)
Following the general procedure (I), the product 3ad was obtained
as brown solid (42.6 mg, 75% yield). Mp = 130 – 131 C. IR (film) ν:
2925, 1576, 1468, 1241, 1070, 1021, 984, 834, 751, 628. H NMR 2-exo-((4-Chlorophenyl)thio)-1,2,3,4-tetrahydro-1,4-
(600 MHz, CDCl3) δ 7.37 (dd, J = 7.2, 1.2 Hz, 1H), 7.27 – 7.21 (m, 3H), epoxynaphthalene (3ai)
o
1
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Following the general procedure (I), the product 3ai was obtained 125.8, 125.4, 119.6, 119.3, 83.3, 79.3, 46.9, 36.0. HRMS calcd for
View Article Online
o
+
DOI: 10.1039/D0OB00659A
as yellow solid (47.8 mg, 83% yield). Mp = 72 – 73 C. IR (film) ν: C20H17OS [M+H] : 305.0995. Found: 305.1003.
1
2927, 1476, 1096, 986, 813, 761, 629. H NMR (600 MHz, CDCl3) δ
2-exo-(Thiophen-2-ylthio)-1,2,3,4-tetrahydro-1,4-
7.34 – 7.29 (m, 4H), 7.25 – 7.22 (m, 2H), 7.20 – 7.15 (m, 2H), 5.47 (d,
epoxynaphthalene (3ap)
J = 4.8 Hz, 1H), 5.19 (s, 1H), 3.29 (dd, J = 7.8, 4.2 Hz, 1H), 2.02 – 1.94
Following the general procedure (I), the product 3ap was obtained
as brown oil (32.7 mg, 63% yield). IR (film) ν: 2926, 1461, 1403,
1170, 938, 834, 708, 625. H NMR (600 MHz, CDCl3) δ 7.41 (dd, J =
5.4, 1.2 Hz, 1H), 7.24 (dd, J = 3.6, 1.2 Hz, 1H), 7.22 (d, J = 6.6 Hz, 1H),
7.18 – 7.12 (m, 3H), 7.03 (dd, J = 5.4, 3.6 Hz, 1H), 5.46 (d, J = 3.0 Hz,
1H), 5.29 (s, 1H), 3.14 (dd, J = 6.0, 4.8 Hz, 1H), 1.95 – 1.93 (m, 2H).
(m, 2H). 13C NMR (150 MHz, CDCl3) δ 145.6, 143.6, 135.0, 132.7,
131.4, 129.4, 127.5, 127.1, 119.5, 119.4, 83.2, 79.3, 46.7, 35.8.
HRMS calcd for C16H14ClOS [M+H]+: 289.0448. Found: 289.0453.
1
2-exo-((4-Bromophenyl)thio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3aj)
Following the general procedure (I), the product 3aj was obtained 13C NMR (150 MHz, CDCl3) δ 145.7, 143.6, 134.2, 134.1, 130.0, 127.9,
o
as yellow solid (40.5 mg, 61% yield). Mp = 71 – 72 C. IR (film) ν: 127.4, 127.1, 119.7, 119.2, 83.3, 79.4, 50.8, 35.5. HRMS calcd for
2925, 1471, 1093, 1007, 810, 759, 627. H NMR (600 MHz, CDCl3) δ C14H13OS2 [M+H]+: 261.0402. Found: 261.0408.
1
7.46 – 7.44 (m, 2H), 7.27 – 7.23 (m, 4H), 7.20 – 7.17 (m, 2H), 5.48 (d,
2-exo-(Thiophen-3-ylthio)-1,2,3,4-tetrahydro-1,4-
J = 4.8 Hz, 1H), 5.20 (s, 1H), 3.30 (dd, J = 7.8, 4.2 Hz, 1H), 2.03 – 1.95
epoxynaphthalene (3aq)
(m, 2H). 13C NMR (150 MHz, CDCl3) δ 145.6, 143.7, 135.7, 132.3,
Following the general procedure (I), the product 3aq was obtained
131.5, 127.5, 127.2, 120.6, 119.5, 119.4, 83.2, 79.3, 46.5, 35.8.
as brown oil (30.2 mg, 58% yield). IR (film) ν: 2927, 1458, 1348,
HRMS calcd for C16H14BrOS [M+H]+: 332.9943. Found: 332.9947.
1204, 985, 890, 854, 757, 627. 1H NMR (600 MHz, CDCl3) δ 7.37 (dd,
2-exo-((4-(Trifluoromethyl)phenyl)thio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3ak)
J = 4.8, 3.0 Hz, 1H), 7.27 (dd, J = 3.0, 1.2 Hz, 1H), 7.24 – 7.19 (m, 2H),
7.09 (dd, J = 4.8, 1.2 Hz, 1H), 5.45 (d, J = 4.8 Hz, 1H), 5.21 (s, 1H),
Following the general procedure (I), the product 3ak was obtained 3.22 (dd, J = 7.2, 4.2 Hz, 1H), 1.98 – 1.91 (m, 2H). 13C NMR (150 MHz,
o
as yellow solid (40.6 mg, 63% yield). Mp = 126 – 127 C. IR (film) ν: CDCl3) δ 145.6, 143.8, 131.7, 130.1, 127.4, 127.1, 126.7, 125.0,
1
2924, 1606, 1328, 1166, 1121, 827, 761, 629. H NMR (600 MHz, 119.5, 119.3, 83.3, 79.3, 47.7, 35.7. HRMS calcd for C14H13OS2
CDCl3) δ 7.56 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 7.8 Hz, 2H), 7.31 – 7.26 [M+H]+: 261.0402. Found: 261.0411.
(m, 2H), 7.23 – 7.20 (m, 2H), 5.50 (d, J = 4.8 Hz, 1H), 5.24 (s, 1H),
2-exo-(Pyridine-2-ylthio)-1,2,3,4-tetrahydro-1,4-
3.41 (dd, J = 7.2, 4.2 Hz, 1H), 2.08 (dd, J = 12.6, 7.8 Hz, 1H), 2.02 –
epoxynaphthalene (3ar)
1.99 (m, 1H). 13C NMR (150 MHz, CDCl3) δ 145.5, 143.5 142.3, 128.1,
Following the general procedure (I), the product 3ar was obtained
128.0, 127.9, 127.7, 127.3, 126.0 (q, JCF = 3.6 Hz), 124.2 (q, JCF
=
o
as brown solid (28.1 mg, 55% yield). Mp = 84 – 85 C. IR (film) ν:
270.0 Hz), 119.5, 83.3, 79.3, 45.3, 35.8. 19F NMR (564 MHz, CDCl3) δ
-62.4. HRMS calcd for C17H14F3OS [M+H]+: 323.0712. Found:
323.0719.
2928, 1578, 1454, 1415, 1267, 1125, 986, 893, 837, 758, 735, 631.
1H NMR (600 MHz, CDCl3) δ 8.46 (dq, J = 4.8, 0.6 Hz, 1H), 7.50 – 7.48
(m, 1H), 7.40 – 7.39 (m, 1H), 7.26 – 7.25 (m, 1H), 7.22 – 7.17 (m, 3H),
7.00 (ddd, J = 7.2, 4.8, 1.2 Hz, 1H), 5.47 (d, J = 4.8 Hz, 1H), 5.35 (s,
1H), 3.84 (dd, J = 7.8, 4.8 Hz, 1H), 2.05 – 1.98 (m, 2H). 13C NMR (150
2-exo-([1,1'-Biphenyl]-4-ylthio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3al)
Following the general procedure (I), the product 3al was obtained MHz, CDCl3) δ 159.6, 149.7, 145.5, 144.2, 135.9, 127.3, 127.1, 122.3,
o
as yellow solid (42.9 mg, 65% yield). Mp = 123 – 124 C. IR (film) ν: 120.0, 119.6, 119.2, 84.6, 79.1, 43.1, 34.6. HRMS calcd for
2924, 1479, 1097, 986, 835, 760, 699, 628. 1H NMR (600 MHz, CDCl3) C15H14NOS [M+H]+: 256.0791. Found: 256.0799.
δ 7.60 – 7.55 (m, 4H), 7.47 – 7.43 (m, 4H), 7.35 (tt, J = 7.2, 1.2 Hz,
2-exo-(Cyclohexylthio)-1,2,3,4-tetrahydro-1,4-epoxynaphthalene
1H), 7.26 – 7.24 (m, 2H), 7.20 – 7.16 (m, 2H), 5.48 (d, J = 4.2 Hz, 1H),
(3as)
5.27 (s, 1H), 3.38 (dd, J = 7.8, 4.8 Hz, 1H), 2.05 – 1.99 (m, 2H), 2.03
Following the general procedure (I), the product 3as was obtained
(dd, J = 12.6, 7.8 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 145.6, 143.8,
as brown oil (16.1 mg, 31% yield). IR (film) ν: 2928, 2852, 1449,
140.4, 139.5, 135.6, 130.2, 129.0, 127.9, 127.6, 127.4, 127.1, 127.0,
1267, 989, 837, 759, 629. 1H NMR (600 MHz, CDCl3) δ 7.28 – 7.25 (m,
119.5, 119.4, 83.3, 79.3, 46.4, 35.8. HRMS calcd for C22H19OS [M+H]+:
1H), 7.24 – 7.21 (m, 1H), 7.18 – 7.15 (m, 2H), 5.41 (d, J = 4.8 Hz, 1H),
331.1151. Found: 331.1157.
5.21 (s, 1H), 2.90 (dd, J = 7.8, 4.2 Hz, 1H), 2.87 – 2.82 (m, 1H), 2.02 –
2-exo-(Naphthalen-1-ylthio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3ao)
2.00 (m, 2H), 1.96 (dd, J = 12.6, 7.8 Hz, 1H), 1.90 (dt, J = 12.0, 4.8 Hz,
1H), 1.81 – 1.78 (m, 2H), 1.64 – 1.62 (m, 1H), 1.45 – 1.23 (m, 5H).
Following the general procedure (I), the product 3ao was obtained 13C NMR (150 MHz, CDCl3) δ 145.7, 144.3, 127.2, 126.9, 119.3, 119.3,
as brown paste (41.9 mg, 69% yield). IR (film) ν: 2919, 1567, 1505, 84.5, 79.1, 44.3, 42.8, 37.0, 34.0, 33.9, 26.2, 26.1, 25.9. HRMS calcd
1049, 834, 765, 625. 1H NMR (600 MHz, CDCl3) δ 8.47 (d, J = 8.4 Hz, for C16H21OS [M+H]+: 261.1308. Found: 261.1311.
1H), 7.86 (dd, J = 7.8, 1.2 Hz, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.67 (dd, J
2-exo-(Isobutylthio)-1,2,3,4-tetrahydro-1,4-epoxynaphthalene (3at)
= 7.2, 1.2 Hz, 1H), 7.56 – 7.50 (m, 2H), 7.45 (dd, J = 8.4, 7.2 Hz, 1H),
Following the general procedure (I), the product 3at was obtained
7.23 (d, J = 4.8 Hz, 1H), 7.16 – 7.09 (m, 3H), 5.49 (d, J = 5.4 Hz, 1H),
as yellow oil (22.5 mg, 48% yield). IR (film) ν: 2956, 2869, 1461,
5.23 (s, 1H), 3.35 (dd, J = 7.8, 4.2 Hz, 1H), 2.12 – 2.08 (m, 1H), 2.03
1244, 1205, 988, 930, 893, 838, 760, 629. 1H NMR (600 MHz, CDCl3)
(dd, J = 12.6, 7.8 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 145.7, 143.7,
δ 7.26 – 7.20 (m, 2H), 7.17 – 7.14 (m, 2H), 5.40 (d, J = 4.8 Hz, 1H),
134.1, 133.5, 133.4, 129.5, 128.7, 128.1, 127.3, 127.0, 126.8, 126.5,
5.21 (s, 1H), 2.79 (dd, J = 7.8, 4.2 Hz, 1H), 2.57 (d, J = 7. 2 Hz, 2H),
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1.94 (dd, J = 12.0, 7.8 Hz, 1H), 1.89 – 1.82 (m, 2H), 1.03 (d, J = 6.6 Hz, 6,7-Dibromo-2-exo-(phenylthio)-1,2,3,4-tetrahydro-1V,4ie-w Article Online
3H), 1.02 (d, J = 6.6 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 145.6, epoxynaphthalene (3fb)
DOI: 10.1039/D0OB00659A
144.2, 127.1, 126.8, 119.2, 119.2, 83.7, 79.0, 44.9, 41.5, 35.4, 28.7, Following the general procedure (I), the product 3fb was obtained
o
22.3, 22.2. HRMS calcd for C14H19OS [M+H]+: 235.1151. Found: as yellow solid (42.7 mg, 57% yield). Mp = 95 – 96 C. IR (film) ν:
235.1157.
2926, 1722, 1582, 1478, 1440, 1321, 1089, 991, 876, 845, 741, 694.
1H NMR (600 MHz, CDCl3) δ 7.50 (s, 1H), 7.47 (s, 1H), 7.40 (d, J = 7.2
Hz, 2H), 7.34 (t, J = 7.8 Hz, 2H), 7.27 (d, J = 7.2 Hz, 1H), 5.42 (d, J =
4.2 Hz, 1H), 5.16 (s, 1H), 3.30 (dd, J = 7.8, 4.8 Hz, 1H), 2.02-1.95 (m,
2H). 13C NMR (150 MHz, CDCl3) δ 146.7, 144.9, 135.8, 130.5, 129.4,
127.1, 124.9, 124.8, 123.3, 123.0, 82.7, 78.8, 46.3, 35.4. HRMS calcd
for C16H13Br2OS [M+H]+: 410.9048. Found: 410.9056.
6,7-Dimethyl-2-exo-(phenylthio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3bb)
Following the general procedure (I), the product 3bb was obtained
as yellow solid (46.8 mg, 83% yield). Mp = 69 – 70 C. IR (film) ν:
2925, 1585, 1439, 1028, 980, 850, 739, 605. 1H NMR (600 MHz,
o
CDCl3) δ 7.40 – 7.38 (m, 2H), 7.34 – 7.31 (m, 2H), 7.24 – 7.21 (m, 1H),
7.02 (d, J = 6.0 Hz, 2H), 5.41 (d, J = 4.2 Hz, 1H), 5.16 (s, 1H), 3.31 (dd, 1,4-Dimethyl-2-exo-(phenylthio)-1,2,3,4-tetrahydro-1,4-
J = 7.2, 4.2 Hz, 1H), 2.24 (s, 6H), 2.00 – 1.93 (m, 2H). 13C NMR (150 epoxynaphthalene (3gb)
MHz, CDCl3) δ 143.5, 141.7, 136.7, 135.5, 135.1, 129.8, 129.2, 126.5, Following the general procedure (I), the product 3gb was obtained
120.8, 120.7, 83.2, 79.2, 46.6, 36.1, 20.1, 20.1. HRMS calcd for as brown oil (45.7 mg, 81% yield). IR (film) ν: 3051, 2974, 2930,
C18H19OS [M+H]+: 283.1151. Found: 283.1155.
1582, 1477, 1442, 1382, 1344, 1277, 1181, 1154, 1096, 861, 742,
695, 662, 622. 1H NMR (600 MHz, CDCl3) δ 7.35 – 7.34 (m, 2H), 7.27
– 7.23 (m, 2H), 7.21 – 7.18 (m, 2H), 7.18 – 7.16 (m, 1H), 7.16 – 7.13
(m, 2H), 3.45 (dd, J = 8.4, 4.8 Hz, 1H), 2.24 (dd, J = 12.6, 7.8 Hz, 1H),
1.86 (dd, J = 12.6, 4.2 Hz, 1H), 1.82 (s, 3H), 1.80 (s, 3H). 13C NMR
(150 MHz, CDCl3) δ 148.5, 147.9, 137.1, 129.8, 129.0, 127.2, 127.0,
126.2, 118.2, 117.8, 87.5, 84.5, 52.3, 45.5, 17.4, 15.6. HRMS calcd
for C18H19OS [M+H]+: 283.1151. Found: 283.1158.
6,7-Dimethoxy-2-exo-(phenylthio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3cb)
Following the general procedure (I), the product 3cb was obtained
o
as yellow solid (50.2 mg, 80% yield). Mp = 112 – 113 C. IR (film) ν:
2925, 1662, 1490, 1309, 1087, 851, 692. 1H NMR (600 MHz, CDCl3) δ
7.42 – 7.40 (m, 2H), 7.35 – 7.32 (m, 2H), 7.26 – 7.23 (m, 1H), 6.86 (s,
1H), 6.83 (s, 1H), 5.42 (d, J = 4.2 Hz, 1H), 5.18 (s, 1H), 3.86 (s, 3H),
3.86 (s, 3H), 3.29 (dd, J = 7.2, 4.8 Hz, 1H), 1.99 – 1.93 (m, 2H). 13C 2-exo-(Phenylthio)-1,2,3,4-tetrahydro-1,4-epoxytriphenylene (3hb)
NMR (150 MHz, CDCl3) δ 148.5, 148.2, 138.1, 136.5, 136.0, 130.1, Following the general procedure (I), the product 3hb was obtained
129.2, 126.6, 104.2, 104.0, 83.5, 79.5, 56.5, 56.4, 46.7, 36.3. HRMS as yellow solid (51.7 mg, 73% yield). Mp = 138 – 139 C. IR (film) ν:
calcd for C18H19O3S [M+H]+: 315.1049. Found: 315.1056.
o
1
2926, 1582, 1441, 1156, 1022, 836, 756, 619. H NMR (600 MHz,
CDCl3) δ 8.66 – 8.65 (m, 2H), 7.85 – 7.83 (m, 1H), 7.66 – 7.64 (m, 1H),
7.62 – 7.57 (m, 4H), 7.44 – 7.42 (m, 2H), 7.35 – 7.33 (m, 2H), 7.26 (tt,
J = 7.2, 1.2 Hz, 1H), 6.04 (d, J = 4.2 Hz, 1H ), 5.74 (s, 1H), 3.27 (dd, J =
7.8, 4.2 Hz, 1H), 2.07 (dt, J = 12.0, 4.8 Hz, 1H), 1.94 (dd, J = 12.0, 7.8
Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 140.9, 138.7, 136.7, 130.4,
130.3, 129.8, 129.2, 127.2, 127.2, 126.6, 126.5, 125.7, 125.6, 124.2,
123.9, 123.8, 123.7, 82.7, 78.9, 46.1, 35.2. HRMS calcd for C24H19OS
[M+H]+: 355.1151. Found: 355.1159.
5,8-Dimethoxy-2-exo-(phenylthio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3db)
Following the general procedure (I), the product 3db was obtained
as brown solid (48.3 mg, 77% yield). Mp = 86 – 87 C. IR (film) ν:
2926, 1584, 1499, 1438, 1259, 1084, 1005, 798, 738, 692, 626. H
NMR (600 MHz, CDCl3) δ 7.40 – 7.38 (m, 2H), 7.32 – 7.29 (m, 2H),
7.20 – 7.18 (m, 1H), 6.66 (s, 2H), 5.63 (d, J = 4.8 Hz, 1H), 5.44 (s, 1H),
3.78 (s, 3H), 3.76 (s, 3H), 3.34 (dd, J = 7.8, 4.2 Hz, 1H), 2.03 (dd, J =
12.6, 7.8 Hz, 1H), 1.94 (dt, J = 12.0, 4.8 Hz, 1H). 13C NMR (150 MHz, 2-exo-(Phenylthio)-9-tosyl-1,2,3,4-tetrahydro-1,4-
CDCl3) δ 147.0, 146.8, 137.1, 134.5, 132.9, 129.1, 128.6, 125.9, epiminonaphthalene (3ib)
o
1
111.9, 111.8, 81.4, 77.2, 56.3, 56.2, 45.1, 35.0. HRMS calcd for Following the general procedure (I), the product 3ib was obtained
C18H19O3S [M+H]+: 315.1049. Found: 315.1057.
as brown paste (43.1 mg, 53% yield). IR (film) ν: 2956, 2923, 2853,
1461, 1344, 1161, 1090, 1024, 813, 750, 685, 605. 1H NMR (600
MHz, CDCl3) δ 7.41 – 7.36 (m, 4H), 7.34 – 7.32 (m, 2H), 7.28 – 7.25
(m, 1H), 6.94 (d, J = 7.8 Hz, 2H ), 6.92 – 6.86 (m, 4H), 5.09 (d, J = 4.2
Hz, 1H), 4.85 (s, 1H), 3.16 (dd, J = 8.4, 4.2 Hz, 1H), 2.25 (s, 3H), 2.13
(dt, J = 12.0, 4.2 Hz, 1H), 1.91 (dd, J = 12.6, 8.4 Hz, 1H). 13C NMR
(150 MHz, CDCl3) δ 143.6, 143.1, 141.8, 135.9, 135.3, 131.0, 129.3,
129.1, 128.1, 127.3, 127.1, 127.0, 120.5, 120.4, 68.3, 63.6, 47.6,
36.6, 21.5. HRMS calcd for C23H22NO2S2 [M+H]+: 408.1086. Found:
408.1090.
6,7-Difluoro-2-exo-(phenylthio)-1,2,3,4-tetrahydro-1,4-
epoxynaphthalene (3eb)
Following the general procedure (I), the product 3eb was obtained
as brown oil (45.2 mg, 78% yield). IR (film) ν: 2927, 1617, 1479,
1358, 1267, 1195, 1061, 854, 793, 742, 694, 616. 1H NMR (600 MHz,
CDCl3) δ 7.41 – 7.39 (m, 2H), 7.35 – 7.33 (m, 2H), 7.28 – 7.25 (m, 1H),
7.08 – 7.03 (m, 2H), 5.44 (d, J = 3.0 Hz, 1H), 5.18 (s, 1H), 3.29 (dd, J =
6.6, 4.8 Hz, 1H), 1.99 – 1.97 (m, 2H). 13C NMR (150 MHz, CDCl3) δ
149.6 (dd, JCF = 246.2, 12.8 Hz), 149.4 (dd, JCF = 246.3, 13.5 Hz),
141.6 (dd, JCF = 5.7, 3.3 Hz), 139.8 (dd, JCF = 5.7, 3.3 Hz), 135.9, 130.4, Tert-butyl-2-exo-(phenylthio)-1,2,3,4-tetrahydro-1,4-
129.4, 127.0, 109.6 (d, JCF = 19.7 Hz), 109.5 (d, JCF = 19.7 Hz), 83.0, epiminonaphthalene-9-carboxylate (3jb)
79.1, 46.5, 35.6. 19F NMR (564 MHz, CDCl3) δ -138.5 (d, J = 19.2 Hz ), Following the general procedure (I), the product 3jb was obtained
-139.0 (d, J = 19.7 Hz ). HRMS calcd for C16H13F2OS [M+H]+: 291.0650. as yellow oil (42.3 mg, 60% yield). IR (film) ν: 3055, 2975, 2930,
Found: 291.0658.
1705, 1583, 1477, 1458, 1368, 1279, 1253, 1169, 1088, 748, 695. 1H
NMR (600 MHz, CDCl3) δ 7.42 (d, J = 7.2 Hz, 2H ), 7.33 (t, J = 7.8 Hz,
2H ), 7.26 – 7.20 (m, 3H), 7.16 – 7.12 (m, 2H), 5.25 (s, 1H), 5.05 (s,
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Organic & Biomolecular Chemistry
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ARTICLE
1H), 3.26 (s, 1H), 2.00 (dt, J = 12.0, 4.8 Hz, 1H), 1.90 (dd, J = 12.6, 7.8 NMR (600 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 2H), 7.26 – 7.21 (m, 2H),
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Hz, 1H), 1.41 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 155.3, 148.4, 7.17 – 7.14 (m, 2H), 7.01 (d, J = 9.0 Hz, 2H),D5O.7I:710(.s1,013H9/)D, 05O.4B40(0d6,5J9A=
145.3, 143.6, 136.3, 130.4, 129.2, 127.2, 126.8, 120.1, 119.8, 80.4, 4.8 Hz, 1H), 3.86 (s, 3H), 3.23 (dd, J = 7.8, 4.2 Hz, 1H), 2.43 (dt, J =
65.4, 60.5, 47.9, 35.4, 28.4. HRMS calcd for C21H24NO2S [M+H]+: 12.0, 4.8 Hz, 1H), 1.75 (dd, J = 12.0, 8.4 Hz, 1H ). 13C NMR (150 MHz,
354.1522. Found: 354.1531.
CDCl3) δ 163.8, 145.5, 143.1, 130.8, 129.8, 127.5, 127.2, 119.5,
119.3, 114.5, 79.3, 79.0, 65.8, 55.7, 31.0. HRMS calcd for C17H17O4S
[M+H]+: 317.0842. Found: 317.0850.
3-exo-((4-Methoxyphenyl)thio)-1-exo-methyl-1,2,3,4-tetrahydro-
1,4-epoxynaphthalene (3la) and 2-exo-((4-Methoxyphenyl)thio)-1-
exo-methyl-1,2,3,4-tetrahydro-1,4-epoxynaphthalene (3la')
Imino(4-methoxyphenyl)(1,2,3,4-tetrahydro-1,4-epoxynaphthalen-
Following the general procedure (I), the product 3la and 3la' was 2-exo-yl)-λ6-sulfanone (6)
obtained as yellow oil (44.7 mg, 3la : 3la' = 2 : 1, 75% yield in total). Following the general procedure (III), the product 6 was obtained as
IR (film) ν: 2929, 1592, 1493, 1460, 1285, 1245, 1177, 1030, 974, yellow oil (138.6 mg, dr = 1.54 : 1, 88% yield in total). IR (film) ν:
829, 761, 648, 619. 3ja: 1H NMR (600 MHz, CDCl3) δ 7.44 – 7.42 (m, 3320, 3274, 2963, 2926, 1593, 1495, 1460, 1311, 1259, 1224, 1125,
1
2H), 7.19 – 7.13 (m, 4H), 6.89 – 6.86 (m, 2H), 5.10 (s, 1H), 3.80 (s, 1018, 987, 838, 763. 6 (major) H NMR (600 MHz, CDCl3) δ 7.94 –
3H), 3.24 (dd, J = 7.8, 4.2 Hz, 1H), 1.99 (dd, J = 12.0, 7.8 Hz, 1H), 1.85 7.91 (m, 2H), 7.30 – 7.29 (m, 1H), 7.22 – 7.21 (m, 1H), 7.16 – 7.14
(s, 3H), 1.65 (dd, J = 12.0, 4.2 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ (m, 2H), 7.00 (d, J = 4.2 Hz, 2H), 5.89 (s, 1H), 5.44 (d, J = 4.2 Hz, 1H),
159.4, 147.9, 144.6, 134.0, 127.2, 126.9, 126.8, 119.3, 118.0, 114.8, 3.85 (s, 3H), 3.36 – 3.32 (m, 1H), 3.29 (brs, 1H), 2.44 – 2.39 (m, 1H),
1
82.5, 77.9, 55.4, 50.7, 41.3, 17.4. 3ja': H NMR (600 MHz, CDCl3) δ 1.76 – 1.68 (m, 1H ). 13C NMR (150 MHz, CDCl3) δ 163.4, 145.9,
7.38 – 7.35 (m, 2H), 7.13 – 7.10 (m, 4H), 6.83 – 6.81 (m, 2H), 5.30 (t, 143.1, 132.2, 131.1, 127.4, 127.0, 119.5, 119.3, 114.3, 79.8, 79.1,
1
J = 2.4 Hz, 1H), 3.77 (s, 3H), 3.22 (t, J = 6.0 Hz, 1H), 2.11 – 2.10 (m, 67.0, 55.6, 31.9. 6 (minor) H NMR (600 MHz, CDCl3) δ 7.94 – 7.91
1H), 2.10 – 2.09 (m, 1H), 1.83 (s, 3H). 13C NMR (150 MHz, CDCl3) δ (m, 2H), 7.28 – 7.26 (m, 1H), 7.22 – 7.21 (m, 1H), 7.16 – 7.14 (m, 2H),
159.0, 147.2, 146.4, 133.6, 127.0, 126.9, 126.2, 118.9, 118.3, 114.7, 6.98 (d, J = 4.2 Hz, 2H), 5.85 (s, 1H), 5.42 (d, J = 4.8 Hz, 1H), 3.84 (s,
88.2, 86.3, 55.4, 51.7, 39.5, 15.6. HRMS calcd for C18H19O2S [M+H]+: 3H), 3.36 – 3.32 (m, 1H), 3.29 (brs, 1H), 2.44 – 2.39 (m, 1H), 1.76 –
299.1100. Found: 299.1105.
1.68 (m, 1H ). 13C NMR (150 MHz, CDCl3) δ 163.4, 145.8, 143.1,
132.2, 131.1, 127.4, 127.0, 119.4, 119.4, 114.3, 79.8, 78.8, 66.6,
55.6, 31.2. HRMS calcd for C17H18NO3S [M+H]+: 316.1002. Found:
316.1007.
3-exo-((4-Methoxyphenyl)thio)-1-exo-acetyl-1,2,3,4-tetrahydro-
1,4-epoxynaphthalene (3ma) and 3-exo-((4-Methoxyphenyl)thio)-
1-exo-acetyl-1,2,3,4-tetrahydro-1,4-epoxynaphthalene (3ma')
Following the general procedure (I), the product 3ma and 3ma' was Experimental procedure for the synthesis of product 3aa on a 1
obtained as yellow oil (44.3 mg, 3ma : 3ma' = 1 : 2, 68% yield in mmol scale
total). IR (film) ν: 2927, 1715, 1592, 1494, 1460, 1363, 1286, 1247, Oxabenzonorbornadiene 1a (144 mg, 1 mmol), KSAc (457 mg, 4
1178, 1030, 828, 762, 639. 3ma: 1H NMR (600 MHz, CDCl3) δ 7.46 – mmol), 4-iodoanisole 2a (468 mg, 2 mmol), Cu(acac)2 (52 mg, 0.2
7.43 (m, 2H), 7.34 – 7. 31 (m, 1H), 7.20 – 7.18 (m, 1H), 7.15 (td, J = mmol), and DMF (10 mL) were simultaneously added to a 25 mL
7.2, 1.2 Hz, 2H), 6.90 – 6.88 (m, 2H), 5.27 (s, 1H), 3.82 (s, 3H), 3.20 round-bottomed flask. Then the mixture was stirred at 130 oC for 24
(dd, J = 7.8, 4.2 Hz, 1H), 2.38 (s, 3H), 2.20 (dd, J = 12.6, 7.8 Hz, 1H), h under air. After cooling to the room temperature, the reaction
1.89 (dd, J = 12.6, 3.6 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 206.4, mixture was poured into the distilled water (100 mL) and extracted
159.8, 143.9, 143.5, 134.7, 127.7, 127.6, 125.4, 119.7, 119.1, 115.0, three times with dichloromethane (3×50 mL). The organic layers
92.0, 83.4, 55.5, 49.5, 38.1, 26.9. 3ma': 1H NMR (600 MHz, CDCl3) δ were combined, washed with brine, dried over Mg2SO4, and then
7.40 (d, J = 7.2 Hz, 1H), 7.35 – 7.33 (m, 2H), 7.22 (d, J = 7.2 Hz, 1H), concentrated in vacuo. The residue was purified by silica gel column
7.20 – 7.18 (m, 2H), 6.84 – 6.81 (m, 2H), 5.47 (d, J = 4.8 Hz, 1H), 3.78 chromatography (using 10% ethyl acetate/petroleum ether as
(s, 3H), 3.41 (dd, J = 7.8, 4.2 Hz, 1H), 2.48 (s, 3H), 2.29 – 2.25 (m, 1H), eluent) to give the corresponding product 3aa in 66% yield (187 mg).
2.12 (dd, J = 12.6, 7.8 Hz, 1H). 13C NMR (150 MHz, CDCl3) δ 206.0,
Conflicts of interest
159.5, 145.2, 142.6, 134.2, 127.9, 127.1, 125.9, 119.9, 119.1, 114.7,
94.7, 78.4, 55.4, 51.7, 39.6, 29.4. HRMS calcd for C19H19O3S [M+H]+:
There are no conflicts to declare.
327.1049. Found: 327.1054.
ACKNOWLEDGMENTS
Bis(4-methoxyphenyl)sulfane (4)
This project is supported by the National Natural Science
Foundation of China (21172081 and 21372090), the Natural Science
Foundation of Guangdong Province (S2013020013091), and the City
of Guangzhou Science and Technology Plan Projects
(201510010054).
Following the general procedure (I), the product 4 was obtained as
light yellow solid (6.8 mg, 14% yield). Mp = 41 – 42 C. IR (film) ν:
2928, 2836, 1591, 1491, 1285, 1243, 1173, 1030, 834, 624. 1H NMR
(600 MHz, CDCl3) δ 7.29 – 7.26 (m, 4H), 6.84 – 6.81 (m, 4H), 3.77(s,
6H). 13C NMR (150 MHz, CDCl3) δ 159.1, 132.8, 127.6, 114.9, 55.5.
HRMS calcd for C14H15O2S [M+H]+: 247.0787. Found: 247.0794.
o
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2-exo-((4-Methoxyphenyl)sulfonyl)-1,2,3,4-tetrahydro-1,4-
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o
yellow solid (113.8 mg, 90% yield). Mp = 108 – 109 C. IR (film) ν:
1
2952, 1594, 1497, 1461, 1295, 1261, 1144, 1089, 889, 838, 763. H
8 |
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Organic & Biomolecular Chemistry
Page 10 of 10
ARTICLE
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DOI: 10.1039/D0OB00659A
TOC
R1
R1
X
S
Cu(acac)2
DMF, 24 h, 130 o
R
X
R2
KSAc
H2O
R
I
C
H
R = aryl or alkyl
R2
Multicomponent one-pot reaction
Diastereoselective syn-addition
Ligand-free
X = O, NBoc, NTs
32 examples
up to 84% yield
A novel copper-catalyzed multicomponent one-pot syn-selective
hydrothioetherification of oxa(aza)bicyclic alkenes to synthesize
unsymmetrical thioethers has been established.
10 |
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