Enantioselective α-functionalization of 1,3-dithianes by iridium-catalyzed allylic substitution

Article abstract of DOI:10.1021/acs.joc.0c01683

An iridium-catalyzed asymmetric allylic substitution reaction with 2-alkoxy carbonyl-1,3-dithianes has been achieved with high regio- and enantioselectivities. The transformation provides a new method for the enantioselective α-functionalization of dithianes. The corresponding dithiane-containing products are easily converted into many other derivatives with high yields and enantioselectivities.

Full text of DOI:10.1021/acs.joc.0c01683

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Article
Enantioselective #-Functionalization of 1, 3-
Dithianes by an Iridium Catalyzed Allylic Substitution
Panpan Wang, Qian Jiang, Ruibo Zhao, Xingang Xie, Shouchu Tang, and Xiaolei Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01683 • Publication Date (Web): 10 Sep 2020
Downloaded from pubs.acs.org on September 12, 2020
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Enantioselective α-Functionalization of 1, 3-Dithianes by an Iridium
Catalyzed Allylic Substitution
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Panpan Wang,† Qian Jiang,† Ruibo Zhao,† Xingang Xie,*† Shouchu Tang,*†‡ Xiaolei Wang*†
†State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, P.
R. China
‡ School of Pharmacy, Lanzhou University, Lanzhou 730000, P. R. China
E-mail: xiexg@lzu.edu.cn
E-mail: tangshch@lzu.edu.cn
E-mail: wangxiaolei@lzu.edu.cn
Supporting Information Placeholder
intermolecular coupling
[Ir]*
intramolecular rearrangement
S
R1
OCO2Me
S
[Ir]*
S
S
CO2R2
+
S
R1
*
K3PO4
K3PO4 / KOt-Bu
R1
O
O
MeO2C
R2 = Me or H
S
24
10
substrates
substrates
99%
mild basic condition, modest to high yield and up to
ee
ABSTRACT: An iridium-catalyzed asymmetric allylic substitution reaction with 2-alkoxy carbonyl-1,3-dithianes has been achieved
with high regio- and enantio-selectivities. The transformation provides a new method for the enantioselective α-functionalization of
dithianes. The corresponding dithiane-containing products are easily converted into many other derivatives with high yields and
enantioselectivities.
■ INTRODUCTION
1,3-Dithiane derivatives are considered as useful acyl anion
group tolerance and powerful efficiency for constructing a
chiral center with high regio- and enantio-selectivities.7 And it
was widely used in the synthesis of natural products and
equivalents, which have been widely used as masked
nucleophilic acylating agents, since the pioneering work of
Corey and Seebach.1 On the other hand, the 1,3-dithiane unit
was also used as the mask of methylene and difluoromethylene
groups due to its variability under a reductive or an oxidative
condition (Scheme 1a).2 The application of 1,3-dithiane was
further explored in total syntheses of natural products, known
as the anion relay reaction.3 Therefore, 1,3-dithianes are found
to be versatile building blocks for the formation of many
important organic compounds and natural products.4,5 However,
the catalytic enantioselective addition reactions of 1,3-dithianes
are still largely unexplored due to they are incompatibility with
other catalytic reaction system. So far, only a few papers
reported the enantioselective addition reaction of 1,3-dithianes
with different electrophiles in a catalytic manner.6 Especially,
the Terada group successfully performed the asymmetric 2-
alkoxycarbonyl-1,3-dithiane addition of imines assisted by
Scheme 1. Representative forms of enantioselective α-
functionalization of dithianes
a). 1,3-dithiane synthon
O
R1 CH2
S
S
R1
R1
b). Terada's work: chiral super base catalyzed asymmetric dithiane addition
PG
H
PG
N
(M-1)*
NaHMDS
HN
Ar
+
RO2C
S
Ar
EtOAc, -40 o
C
S
S
CO2R
S
c). Zhang's work: palladium catalyzed asymmetric dithiane substitution
OBoc
bis(guanidino)amino-phosphorane
enantioselectivity and good yields. (Scheme 1b).6a Zhang
reported 2-phenyl-1,3-dithiane’s asymmetric allylic
with
excellent
S
Ar
Ar
Ph
Pd/L*
THF, -20 o
+
S
C
substitution with 1,3-diphenylallyl pivalate (Scheme 1c).6b
Previous strategies can only synthesis of specific dithiane
containing products due to the limitation of electrophiles. New
methods are still needed to prepare optically active α-
functionalized 1,3-dithiane derivatives, which are known as
versatile starting materials for further synthetic transformations.
The iridium-catalyzed asymmetric allylic substitution reaction
has attracted considerable attentions due to the wide functional-
S
Ar
Ar
Ph
S
d). This work: iridium catalyzed asymmetric allylic dithiane substitution
R1
R2OC
OCO2Me
S
S
COR3 Ir/L*
R1
Ir/L*
S
S
+
S
R1
O
O
S
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pharmaceutical molecules.8 On the other hand, the Li group
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recently reported dithiane-directed C−H borylation via iridium
catalysis.9 They observed a strong coordination 1,3-dithiane
group with an iridium metal catalyst9, 10 and other transition
metals.11 Inspired by these works, we herein report a new
method to prepare optically active α-functionalized 1,3-dithiane
derivatives by using iridium catalyzed intermolecular and
intramolecular allylic substitution methods (Scheme 1d).
Table 1. Optimization of reaction conditionsa
[Ir(cod)Cl]2 2%
S
Ph
OCO2Me
L1
(S, S, S)- 4%
CO2Me
1a
TBD 10%
S
+
S
S
base, additive, 50 oC.
Ph
CO2Me
2a
3aa
■ RESULTS AND DISCUSSION
Ph
O
9
P
N
Initially, allylic ester 1a and 1,3-dithiane derivative 2a were used
as the model substrate. The reaction was carried out by using a
common Ir-catalytic system consisting of [Ir(cod)Cl]2 and a chiral
ligand with a variety of bases13 under an argon atmosphere in THF
at 50 ℃ for 6 h. First, the effect of the ligand on the reaction was
examined.7d, e, f L1 was found to be a suitable ligand obtaining the
desired coupling product 3a with 27% yield and 95% ee (Table 1,
entry 1). The low yield could attribute to the decomposition of ester
1a and the formation of a hydrolysis byproduct with 1.5 equivalents
t-BuOK as a base. Other strong bases did not improve the yield
(Table 1, entries 2-7). However, a clean reaction was obtained by
using K3PO4 as the base, giving 3a in 41% yield together with 55%
recovered 1a (Table 1, entry 8). Prolonging the reaction time and
increasing the amount of K3PO4 or adding additives, such as 4ÅMS,
18-crown-6, CsF, or LiCl, did not give any positive result (Table 1,
entries 9-12). Further experiments revealed that the choice of a
suitable mixture of bases was important for the allylic substitution
reaction. To our delight, the desired product was obtained with 78%
yield by using a mixture of 3.0 equiv. K3PO4 and 0.2 equiv. t-BuOK
as combined bases (Table 1, entry 13). The mixture of bases might
provide a buffer system to accelerate the reaction and lower down
the hydrolysis of the dithiane ester. After an extensive screening
process, the reaction conditions were optimized as follows: the
coupling reaction was performed with 3.0 equivalent K3PO4, 0.2
equivalent t-BuOK, 2 mol% [Ir(cod)Cl]2, 4 mol% (S, S, S)-L1 and
10 mol% TBD in THF at 50 ℃ for 6 h. Besides, no linear product
was observed in this reaction system. The coordination of 1,3-
dithiane motif with the iridium catalyst might help explain the
observed excellent regioselectivity.
O
10
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Ph
L1
(S, S, S)-
entry
bases
additive
yieldb
eec
1
t-BuOK
t-BuOLi
t-BuONa
LiHMDS
DBU
27
25
22
11
10
23
15
41
37
31
33
29
78
76
95
94
95
94
96
94
95
94
95
95
93
98
98
98
2
3
4
5
6f
7g
8d
9
t-BuOK
t-BuOK
K3PO4
K3PO4
LiCl
10
11
12
13
14e
K3PO4
18-crown-6
CsF
K3PO4
K3PO4
4ÅMS
t-BuOK
t-BuOK
K3PO4
K3PO4
aUnless otherwise noted, the reaction of 1a (0.1 mmol) with 2a
(0.15 mmol) was carried out by using a catalytic system consisting
of [Ir(cod)Cl]2 (2 mol%) and (S, S, S)-L1 (4 mol%) and 10 mol%
TBD under an Ar atmosphere in the presence of a base (0.11 mmol)
and an additive (0.02 mmol) in THF (2 mL) at 50 ℃ for 6 h. TBD=1,
b
5, 7-Triazabicyclo[4. 4. 0] dec-5-ene. Isolated yields. cDetermined
With the optimized conditions in hand, the scope of aryl
allylic esters was investigated. First, ortho-, meta-, and para-
aryl esters were tested, and the corresponding products 3b-3d
were obtained with high yields and high enantioselectivities.
Esters with an electron-donating group, such as a methyl and a
methoxy group, or an electron-withdrawing group, such as a
floro, a chloro, or a bromo group, smoothly underwent the
reaction to produce products 3d-3f with high yields and
excellent enantioselectivities. The steric hindering substituent
on the aromatic ring, such as an i-Pr or a t-Bu group at the para
position proceeded without any problems. The naphthyl or the
benzo-furanyl ring showed little influence on this reaction,
affording the corresponding products 3g, 3h, and 3i with high
yields and high enantioselectivities, respectively. More
importantly, heteroaromatic esters were also found to be
tolerant in this reaction. Furyl and thionyl esters were found to
be compatible with the reaction conditions and produced the
products 3j and 3p-3r with excellent yields. The substitution of
1,3-dithianes also exerted little influence on this reaction.
Particularly, the proton of 2-acetyl 1,3-dithiane also did not
show any impact on this allylic substitution, affording the
product 3x with excellent regioselectivity. Fortunately, a crystal
of 3x was obtained, which further confirmed the absolute
configuration of the stereocenters in the products depicted in
Table 2.
by HPLC using a chiral Daicel OD-H column. dK3PO4 (3.0 equiv.)
e
was used with 55% recovery of starting material 1a. At room
temperature for 14 h. fDCM was used as solvent. gDMSO was used
as solvent.
The intramolecular reaction of 4a was also examined in the
presence of 2 mol% [Ir(cod)Cl]2, 4 mol% (R, R, R)-L1 and 10
mol% TBD, with K3PO4 as a base, which provided the acid 5a
as the sole product in 62% yield (condition optimization see SI).
It seems that ester hydrolysis is a more favorable process to
form a dithiane-containing acid than five-membered cyclic
ester formation. The substrate scope of the Ir-catalyzed
intramolecular rearrangement reaction of dithianes 4 was
investigated under the optimized reaction conditions (Table 3).
The reaction proceeded well in all cases, yielding dithiane-
containing acid 5a-5d with moderate yields and high
enantioselectivities. Substitution on the aryl group of substrates
exerted little influence on the intramolecular allylic substitution
reactions. Most importantly, the reaction also proceeded well
for alkyl-substituted allylic ester 4e, providing the
corresponding product 5e with excellent ee and moderate yield.
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Table 2. Scope of the intermolecular enantioselective α-
functionalization of dithianesa
Table 3. Scope of the intramolecular enantioselective α-
functionalization of dithianesa
4
5
6
7
O
S
O
[Ir(cod)Cl]2 2%
S
O
[Ir(cod)Cl]2 2%
O
L1
(R, R, R)- 4%
S
L1
(S, S, S)- 4%
R
OH
S
S
TBD 10%
R
S
R
TBD 10%
R
O
S
2
+
K3PO4
S
Ar
K3PO4, t-BuOK (cat.)
4
5
Ar
OCO2Me
3
1
8
9
O
O
O
S
S
O
O
S
S
O
S
S
10
11
12
13
14
15
16
17
18
19
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21
22
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O
OH
O
S
O
S
OH
OH
S
S
S
S
3a
3b
3c
O
78%, 98%ee
81%, 98%ee
76%, 92%ee
5a
5b
5c
O
S
O
S
O
S
62%, 98%ee
55%, 85%ee
57%, 99%ee
O
O
O
S
S
S
O
S
O
S
F
3d
Cl
3e
Br
3f
OH
S
71%, 91%ee
73%, 94%ee
69%, 99%ee
OH
S
O
S
O
S
O
S
O
O
5d
5e
5e
O
S
S
S
59%, 96%ee
51%, 96%ee
CCDC:1960101
O
S
O
S
MeO
3g
3i
O
S
3h
71%, 98%ee
95%, 99%ee
76%, 95%ee
OH
S
OH
OH
S
S
O
S
O
S
O
S
O
O
S
O
F
S
Br
Cl
S
5g
5f
5h
51%, 97%ee
55%, 97%ee
O
54%, 98%ee
3j
3k
3l
75%, 98%ee
67%, 98%ee
73%, 92%ee
O
S
O
S
O
S
OH
O
S
O
S
S
S
OH
S
O
O
S
O
S
MeO
S
5j
5i
60%, 98%ee
67%, 91%ee
OMe
3o
83%, 87%ee
OMe
3n
3m
86%, 94%ee
93%, 97%ee
O
S
O
S
O
S
aThe reaction of 4 (0.1 mmol) was carried out by using a catalytic
system consisting of [Ir(cod)Cl]2 (2 mol%) and (R, R, R)-L1 (4
mol%) under an Ar atmosphere in the presence of a base (0.15
mmol) in THF (2 mL) at 50 oC for 6 h. Isolated products; ee values
were determined by HPLC using chiral Daicel columns.
O
O
O
S
S
S
O
S
S
3r
3p
3q
92%, 99%ee
96%, 99%ee
95%, >99%ee
O
S
O
S
O
S
The absolute configuration of the stereocenters in the products
showed in Table 2 was also confirmed through the single-
crystal X-ray diffraction analysis of 5e. Furthermore, the
absolute configurations of the stereocenters in 5a-5d in Table 2
were also indirectly confirmed via comparing the optical
rotation of acid derivative of 3a and 5a. The stereocenter’s
absolute configuration of 5a-5d was conforms to the general
rule of the iridium-catalytic system.
O
O
O
S
S
S
N
3u
3s
3t
75%, 96%ee
77%, 99%ee
73%, 98%ee
O
S
O
S
O
S
OBn
Ph
S
S
S
Scheme 2. Mechanisms of the iridium catalyzed
enantioselective dithaine allylic substitution reaction.
3x
3v
76%, 98%ee
3w
92%, 96%ee
x-ray
CCDC:1966888
83%, 94%ee
aThe reaction of 1 (0.1 mmol) with 2 (0.15 mmol) was carried out
by using a catalytic system consisting of [Ir(cod)Cl]2 (2 mol%) and
(S, S, S)-L1 (4 mol%) under an Ar atmosphere in the presence of
K3PO4 (0.30 mmol) and t-BuOK (0.02 mmol) in THF (2 mL) at 50
oC for 6 h. Isolated products; ee values were determined by HPLC
using chiral Daicel columns.
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R1
OCO2Me
S
COR2
acid 5a could further transformed into lactone 10 in high yield
via intramolecular esterification.
L*
[Ir(cod)Cl]2, , TBD
1
S
R1
1
2
+
S
S
base, temp.
COR2
3
2
3
4
5
6
7
8
9
R2OC
In conclusion, we have developed a catalytic enantioselective
α-functionalization of 1,3-dithianes by using an iridium
catalyzed allylic substitution. The allylic substitution has
proceeded in a highly enantioselective manner to produce
optically active dithiane-containing compounds, which are
known as valuable versatile building blocks in organic synthesis.
Ongoing studies are focused on the development of novel
enantioselective transformations for the synthesis of dithiane-
containing compounds.
S
COR2
S
S
S
2
R1
base
O
O
R1
Ir
P
N
Ir
P
N
O
Ph
Ph
Ph
II
OCO2Me
O
Ph
1
III
R1
10
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COR2
S
O
O
S
COR2
Ir
P
N
S
R1
S
R1
Ir
3
Ph
P
Ph
O
I
O
■ EXPERIMENTAL SECTION
N
Ph
General Information 1H NMR spectra were recorded on a Bruker
Mercury 400, 600MHz spectrometer in CDCl3. Chemical shifts are
reported in ppm with the internal TMS signal at 0.0 ppm as a
standard. The data are reported as (s = single, d = double, t = triple,
q = quartet, m = multiple or unresolved, and br = broad). 13C NMR
spectra were recorded on a Bruker 100 MHz spectrometer in
CDCl3. Chemical shifts are reported in ppm. Commercially
available reagents were used without further purification. All
reactions were monitored by TLC with silica gel plates.
Ph
IV
Based on the initial studies of Hartwig and previous
literature7, a plausible reaction pathway was proposed (Scheme
2). Allylic ester 1 coordinates to a chiral Ir catalyst I to give the
intermediate II.7 Owing to the coordination of dithiane with the
iridium catalyst,9 2-alkoxycarbonyl-1, 3-dithiane anion and
cationic Ir intermediate II might form a complex transition state
III. Then, a nucleophilic allylic substitution reaction occurs
between the α-position of the dithiane derivative and the allylic
cation, in which the stereo-chemical outcome is controlled by
the chiral ligand of iridium in an enantio- and regioselective
manner.12
Enantiomeric ratios were determined by HPLC, using
a
CHIRALPAK AD-H And OD-H with hexane and i-PrOH as
solvents. HRMS was tested by a Bruker Daltonics Apex II 47e
Specifications. The mass analyzer type Q-TOF used for the HRMS
measurements. The melting points were determined in glass
capillary tubes using WRS-2U melting point apparatus (Shanghai
precision Instrument Co. Ltd. Shanghai, China) and are
uncorrected. The crystal date structure was obtained at room
temperature using Mo Kα radiation on a Bruker APEXII
diffractometer X-ray diffraction data were collected on Agilent
SuperNova Eos diffractometer. 1,3-dithiane derivatives (1(Methyl
ester)16d, 1t16c, 1u16a,1v6a, 1w6b and 1x16b) were reported in the
literatures.
Scheme 3. Transformation of enantioenriched α-functionalized
1,3-dithianesa
O
O
a. Raney, MeOH
R = biphenyl
b. Raney, THF
R = biphenyl
O
O
R
R
O
6
S
7
93%, >99% ee
O
95%, 99% ee
S
R
O
S
O
S
General produces for the preparation of compound 1
d. 8M NaOH aq. MeOH
R = Ph
c. wilkinson catalyst
R = Ph
OH
S
O
S
To a stirred suspension of NaH (60% w/w in mineral oil, 2.0 equiv.)
in THF (1.0 M) was added triethylphosphonoacetate (1.5 equiv.) at
0 ºC and was stirred for 20 min before being added with the
appropriate aldehyde (1.0 equiv.) and was allowed to warm to room
temperature. After cooling to 0 ºC the reaction was carefully
quenched with H2O and extracted with EtOAc. The organic layer
was separated, dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The residue was dissolved in Et2O (1.0 M)
and was stirred at -78 ºC when DIBAL-H (1.0 M toluene, 2.5 equiv.)
was added dropwise. The solution was allowed to warm to room
temperature and was stirred for 3-5 h before being quenched with
sat. Rochelle’s salts very slowly followed by H2O, diluted with
EtOAc and was stirred overnight. The organic layer was separated
and dried over anhydrous Na2SO4. After the solvent was removed
in vacuo, the crude product was purified by column
chromatography (silica gel, hexane/EtOAc) to give the
corresponding allylic alcohol. Finally, the residue was dissolved in
dichloromethane (0.5 M), added with DMAP (0.20 equiv.) and
pyridine (3.0 equiv.) and was stirred at 0 ºC for 20 min before
methyl chloroformate (1.5 equiv.) was added dropwise over 10 min.
Then the reaction mixture was allowed to warm to room
temperature and was stirred overnight. The reaction was quenched
with aq. NH4Cl and was poured into EtOAc. The organic layer was
separated and dried over anhydrous Na2SO4. After the solvent was
Ph
99%, 98% ee
Ph
5a
8
O
S
57%, 98% ee
O
S
e. I2, NaHCO3, KI
Ph
I
83%, 99% ee
10
aGeneral reaction conditions: a) Raney-Ni, MeOH, 50 ℃; b)
Raney-Ni, THF, 50 ℃; c) Wilkinson catalyst (5%), H2, THF, RT;
d) NaOH (4.0 equiv, 4 M aq.), MeOH, reflux; e) I2 (1.3 equiv),
NaHCO3 (1.4 equiv), KI (1.3 equiv), MeCN/H2O (1:1), RT.
Finally, the derivative transformations of the optically
dithiane-containing products were performed (Scheme 3). First,
the selective reduction of the 1,3-dithiane and alkene moiety
was investigated. The reduction of the alkene moiety of 3k with
Raney-Ni in MeOH yielded enantioenriched ester 6. Pleasingly,
the selective removal of the 1,3-dithiane moiety was achieved
with Raney-Ni in THF to produce ester 7 in high yield.
Moreover, the hydrogenative of the double bond moiety of (S)-
4a by using the Wilkinson catalyst yielded (S)-8 in good
enantioselectivity. The hydrolysis of (S)-4a under basic
condition was smoothly carried out to produce 5a in good yield
with high enantioselectivity. More importantly, enantio-rich
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removed in vacuo, the crude product was purified by column
(minor) [1.0% i-PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃];
[α]25 D +45.4 (c 0.79, CH2Cl2). HRMS (ESI) m/z: [M+H]+ calcd.
1
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3
4
5
6
7
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chromatography (silica gel, Petroleum ether /EtOAc) to give the
corresponding allylic carbonates.
for C15H19O2S2 295.0821; found 295.0826.
Allylic carbonates 1a-1b15a, 1c15c, 1d-1g15a, 1j-1k15e, 1l15c, 1m-
1o15a, 1p15c, 1q15b, 1r15d and 1s15c were reported in the literatures.
Compound 3b. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (24.9 mg, 81%); 1H NMR (400 MHz, CDCl3) δ 7.26ꟷ
7.22 (m, 2H), 7.09 (d, J = 8.0 Hz, 2H), 6.46 (ddd, J = 16.9, 10.2,
8.8 Hz, 1H), 5.21 (dd, J = 16.9, 10.2 Hz, 2H), 4.01 (d, J = 8.8 Hz,
1H), 3.73 (s, 3H), 3.08 (ddd, J = 15.2, 12.9, 2.8 Hz, 2H), 2.73ꟷ2.65
(m, 2H), 2.31 (s, 3H), 2.06ꟷ2.01 (m, 1H), 1.80 (qt, J = 13.0, 3.4 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.8, 137.3, 135.8,
135.0, 129.4, 128.8, 118.5, 60.6, 57.1, 52.9, 28.5, 28.3, 24.3, 21.1;
The enantiomeric excess was isolated: HPLC Daicel Chiralpak
OD-H column to be 98% with Rt = 8.1 min (minor) and Rt = 8.7
min (major) [1.0% i-PrOH in hexanes, 1 mL/ min, 210 nm, 25 ℃];
[α]25 D +56.1 (c 0.49, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd.
for C16H21O2S2 309.0977; found 309.0981.
Compound 1h. Petroleum ether/ethyl acetate (10:1) as the eluent;
colorless oil (starting from 10 mmol of cuminaldehyde, 1.7 g,
73%); 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.0 Hz, 2H), 7.19
(d, J = 8.0 Hz, 2H), 6.67 (dd, J = 15.8 Hz, 1.4 Hz, 1H), 6.25 (dt, J
= 15.8, 6.5 Hz, 1H), 4.78 (dd, J = 6.4, 1.4 Hz, 2H), 3.80 (s, 3H),
2.93ꟷ2.86 (m, J = 6.9 Hz, 1H), 1.24 (d, J = 6.9 Hz, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 155.7, 149.1, 134.9, 133.6, 126.7, 126.7,
121.4, 68.6, 54.8, 33.9, 23.9; HRMS (ESI) m/z: [M+Na]+ calcd. for
C14H18NaO3 257.1148; found 257.1147.
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Compound 1i. Petroleum ether/ethyl acetate (10:1) as the eluent;
colorless oil (starting from 10 mmol of 4-tert-Butylbenzaldehyde,
2.0 g, 81%); 1H NMR (400 MHz, CDCl3) δ 7.36ꟷ7.30 (m, 4H), 6.66
(dt, J = 15.9, 1.3 Hz, 1H), 6.25 (dt, J = 15.9, 6.5 Hz, 1H), 4.77 (dd,
J = 6.6, 1.3 Hz, 2H), 3.79 (s, 3H), 1.31 (s, 9H); 13C{1H} NMR (100
MHz, CDCl3) δ 155.6, 151.3, 134.6, 133.2, 126.4, 125.5, 121.5,
68.5, 54.7, 34.5, 31.2; HRMS (ESI) m/z: [M+Na]+ calcd. for
C15H20NaO3 271.1305; found 271.1301.
Compound 3c. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (23.4 mg, 76%); 1H NMR (400 MHz, CDCl3) δ 7.20ꟷ
7.13 (m, 3H), 7.06 (dd, J = 6.9, 1.8 Hz, 1H), 6.46 (ddd, J = 16.9,
10.2, 9.1 Hz, 1H), 5.20 (dd, J = 16.9, 10.2 Hz, 2H), 4.01 (d, J = 9.1
Hz, 1H), 3.74 (s, 3H), 3.14ꟷ3.04 (m, 2H), 2.73ꟷ2.65 (m, 2H), 2.33
(s, 3H), 2.07ꟷ2.03 (m, 1H), 1.87ꟷ1.77 (m, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 170.9, 138.1, 137.6, 135.8, 130.5, 128.5, 128.0,
126.6, 118.7, 60.6, 57.6, 53.0, 28.6, 28.4, 24.4, 21.6; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak OD-H
column to be 92% with Rt = 18.2 min (major) and Rt = 20.8 min
(minor) [1.0% i-PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25
D +17.3 (c 0.52, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for
C16H21O2S2 309.0977; found 309.0981.
Gram-Scale Synthesis.
In a 100 mL schlenk flask [Ir(cod)Cl]2 (0.1 mmol), chiral
phosphoramidite (0.2 mmol), and TBD (0.5 mmol) were dissolved
in THF (20 mL) under an Ar atmosphere. The reaction vessel was
sealed with a screw cap and the mixture heated at 50 ℃ (oil bath)
for 30 min to allow the formation of the active catalyst species (the
solution turns from orange to yellow). After this time, 1a (5 mmol),
2a (7.5 mmol), K3PO4 (10 mmol), t-BuOK (1 mmol) and THF (20
mL) were then added and the resulting mixture was heated at 50 ℃.
Upon completion, the solvent evaporated. The mixture was then
purified by flash chromatography to afford the product 3a (1.02g,
72%).
Compound 3d. Petroleum ether/ethyl acetate (40:1) as the eluent;
1
colorless oil (22 mg, 71%); H NMR (400 MHz, CDCl3) δ 7.36
ꟷ7.32 (m, 2H), 7.01ꟷ6.96 (m, 2H), 6.42 (ddd, J = 16.9, 10.2, 8.7
Hz, 1H), 5.19 (dd, J = 16.9, 10.2 Hz, 2H), 4.05 (d, J = 8.7 Hz, 1H),
3.74 (s, 3H), 3.11 (ddd, J = 14.2, 11.4, 2.8 Hz, 2H), 2.74ꟷ2.66 (m,
2H), 2.05 (dtt, J = 14.1, 4.3, 2.8 Hz, 1H), 1.86ꟷ1.76 (m, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 170.7, 135.5, 133.8, 131.3,
118.8, 115.0, 114.7, 60.2, 56.6, 53.0, 28.4, 28.2, 24.2; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak OD-H
column to be 91% with Rt = 15.8 min (minor) and Rt = 16.9 min
(major) [1.0% i-PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25
D +4.1 (c 0.5, CH2Cl2); 19F NMR (282 MHz, CDCl3): δ ꟷ115.2;
HRMS (ESI) m/z: [M+H]+ calcd. for C15H18FO2S2 313.0727; found
313.0729.
Compound 3e. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (23.9 mg, 73%); 1H NMR (400 MHz, CDCl3) δ
7.32ꟷ7.25 (m, 4H), 6.41 (ddd, J = 16.9, 10.2, 8.7 Hz, 1H), 5.20 (dd,
J = 16.9, 10.2 Hz, 2H), 4.04 (d, J = 8.7 Hz, 1H), 3.74 (s, 3H), 3.12
(ddd, J = 14.2, 12.4, 2.8 Hz, 2H), 2.73ꟷ2.66 (m, 2H), 2.08ꟷ2.03 (m,
1H), 1.80 (dtt, J = 13.8, 12.6, 3.4 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 170.7, 136.6, 135.3, 133.5, 131.1, 128.2, 119.1,
59.9, 56.7, 53.0, 28.4, 28.2, 24.2; The enantiomeric excess was
isolated: HPLC Daicel Chiralpak OD-H column to be 94% with Rt
= 21.3 min (minor) and Rt = 22.8 min (major) [1.0% i-PrOH in
hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25 D ꟷ6.5 (c 0.31, CH2Cl2);
HRMS (ESI) m/z: [M+H]+ calcd. for C15H18ClO2S2 329.0431;
found 329.0435.
General produces for the preparation of compound 3.
In
a
reaction vessel [Ir(cod)Cl]2 (0.002 mmol), chiral
phosphoramidite (0.004 mmol), and TBD (0.01 mmol) were
dissolved in THF (0.5 mL) under an Ar atmosphere. The reaction
vessel was sealed with a screw cap and the mixture heated at 50 ℃
(oil bath) for 30 min to allow the formation of the active catalyst
species (the solution turns from orange to yellow). After this time,
the allylic carbonate (0.1 mmol), the nucleophile (0.15 mmol),
K3PO4 (0.2 mmol), t-BuOK (0.02 mmol) and THF (1.5 mL) were
then added and the resulting mixture was heated at 50 ℃ (oil bath).
Upon completion, the solvent evaporated. The mixture was then
purified by flash chromatography to afford the product.
Preparation of Racemic Standards Racemic samples were obtained
by using the above-mentioned procedure, however racemic ligand
was used (S, S, S)-Ligand and (R, R, R)-Ligand at the ratio of 1:1.
Compound 3f. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (25.6 mg, 69%); 1H NMR (400 MHz, CDCl3) δ
7.43ꟷ7.41 (m, 2H), 7.27ꟷ7.24 (m, 2H), 6.40 (ddd, J = 16.9, 10.2,
8.7 Hz, 1H), 5.20 (dd, J = 16.9, 10.2 Hz, 1H), 4.03 (d, J = 8.7 Hz,
1H), 3.74 (s, 3H), 3.12 (ddd, J = 14.2, 12.5, 2.8 Hz, 2H), 2.76ꟷ2.62
(m, 2H), 2.08ꟷ2.03 (m, 1H), 1.80 (dtt, J = 13.9, 12.6, 3.4 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 170.6, 137.1, 135.2, 131.4,
131.1, 121.7, 119.1, 59.8, 58.5, 56.7, 28.2, 24.2, 18.4; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak OD-H
column to be 99% with Rt = 18.5 min (minor) and Rt = 19.8 min
Compound 3a. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (22 mg, 78%); 1H NMR (400 MHz, CDCl3) δ 7.37ꟷ
7.25 (m, 5H), 6.46 (ddd, J = 16.9, 10.1, 8.8 Hz, 1H), 5.22 (dd, J =
16.9, 10.1 Hz, 2H), 4.05 (d, J = 8.8 Hz, 1H), 3.73 (s, 3H), 3.16ꟷ
3.05 (m, 2H), 2.72ꟷ2.66 (m, 2H), 2.06ꟷ2.01 (m, 1H), 1.86ꟷ1.79
(m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.7, 138.1, 135.7,
129.6, 128.0, 127.6, 118.7, 60.4, 57.5, 52.9, 28.5, 28.2, 24.2; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak OD-H
column to be 98% with Rt = 8.6 min (major) and Rt = 9.0 min
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 12
(major) [1.0% i-PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25
D +5 (c 0.2, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for
C15H18BrO2S2 372.9926; found 372.9930.
28.5, 28.3, 24.3; The enantiomeric excess was isolated: HPLC
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3
4
5
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Daicel Chiralpak OD-H column to be 98% with Rt = 11.2 min
(major) and Rt = 12.1 min (minor) [1.0% i-PrOH in hexanes, 1
mL/min, 210 nm, 25 ℃]; [α]25 D –4.2 (c 0.24, CH2Cl2); HRMS
(ESI) m/z: [M+H]+ calcd. for C21H23O2S2 371.1134; found
371.1140.
Compound 3g. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (30.8 mg, 95%); 1H NMR (400 MHz, CDCl3) δ 7.29ꟷ
7.26 (m, 2H), 6.85ꟷ6.81 (m, 2H), 6.44 (ddd, J = 16.9, 10.1, 8.7 Hz,
1H), 5.18 (dd, J = 16.9, 10.1 Hz, 2H), 4.01 (d, J = 8.7 Hz, 1H), 3.78
(s, 3H), 3.74 (s, 3H), 3.10 (ddd, J = 14.3, 12.5, 2.8 Hz, 2H), 2.70
(ddd, J = 12.7, 2.4 Hz, 2H), 2.07ꟷ2.02 (m, 1H), 1.81 (dtt, J = 13.9,
12.5, 3.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.8,
158.9, 135.9, 135.9, 130.7, 118.4, 113.4, 60.7, 56.7, 55.1, 52.9,
28.5, 28.2, 24.3; The enantiomeric excess was isolated: HPLC
Daicel Chiralpak OD-H column to be 99% with Rt = 12.8 min
(major) and Rt = 14.9 min (minor) [1.0% i-PrOH in hexanes, 1
mL/min, 210 nm, 25 ℃]; [α]25 D +45.4 (c 0.22, CH2Cl2). HRMS
(ESI) m/z: [M+H]+ calcd. for C16H21O3S2 325.0927; found
325.0930.
Compound 3h. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (25 mg, 76%); 1H NMR (400 MHz, CDCl3) δ
7.27ꟷ7.25 (m, 2H), 7.16ꟷ7.14 (m, 2H), 6.46 (ddd, J = 16.9, 10.1,
9.0 Hz, 1H), 5.20 (dd, J = 16.9, 10.1 Hz, 2H), 4.01 (d, J = 9.0 Hz,
1H), 3.73 (s, 3H), 3.10 (ddd, J = 14.2, 12.6, 2.8 Hz, 2H), 2.90ꟷ2.83
(m, 1H), 2.74ꟷ2.67 (m, 2H), 2.11ꟷ2.01 (m, 1H), 1.82 (dtt, J = 13.7,
12.6, 3.4 Hz, 1H), 1.22 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 170.8, 148.0, 135.8, 135.3, 129.4, 126.1, 118.5,
60.6, 57.3, 52.9, 33.6, 28.6, 28.3, 24.3, 23.9; The enantiomeric
excess was isolated: HPLC Daicel Chiralpak OD-H column to be
95% with Rt = 8.9 min (minor) and Rt = 9.6 min (major) [1.0% i-
PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25 D +9.2 (c 0.32,
CH2Cl2). HRMS (ESI) m/z: [M+H]+ calcd. for C18H25O2S2
337.1290; found 337.1293.
Compound 3l. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (25 mg, 73%); 1H NMR (600 MHz, CDCl3) δ 8.23 (d,
J = 8.6 Hz, 1H), 7.85 (dd, J = 12.4, 7.7 Hz, 2H), 7.77 (d, J = 8.2
Hz, 1H), 7.56ꟷ7.52 (m, 1H), 7.47 (td, J = 7.5, 4.0 Hz, 2H),
6.56ꟷ6.48 (m, 1H), 5.26ꟷ5.00 (m, 3H), 3.50 (d, J = 1.0 Hz, 3H),
3.18ꟷ3.12 (m, 2H), 2.74ꟷ2.67 (m, 2H), 2.04 (dt, J = 13.7, 3.6 Hz,
1H), 1.83 (dt, J = 12.7, 3.4 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 170.9, 136.1, 134.6, 133.8, 132.2, 128.9, 128.1, 126.8,
125.9, 125.4, 125.0, 123.4, 118.5, 61.3, 52.9, 51.0, 28.9, 28.3, 24.2;
The enantiomeric excess was isolated: HPLC Daicel Chiralpak
AD-H column to be 92% with Rt = 6.0 min (major) and Rt =7.3
min (minor) [2.0% i-PrOH in hexanes, 1 mL/ min, 210 nm, 25 ℃];
[α]25 D +87.3 (c 0.24, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd.
for C19H21O2S2 345.0933; found 345.0939.
Compound 3m. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (29 mg, 86%); 1H NMR (400 MHz, CDCl3) δ
7.81ꟷ7.76 (m, 4H), 7.52 (dd, J = 8.5, 1.9 Hz, 1H), 7.47ꟷ7.41 (m,
2H), 6.57 (ddd, J = 16.9, 10.2, 8.7 Hz, 1H), 5.20 (d, J = 16.9, 10.2
Hz, 2H), 4.24 (d, J = 8.7 Hz, 1H), 3.73 (s, 3H), 3.11 (ddd, J = 14.3,
12.5, 2.8 Hz, 2H), 2.76ꟷ2.64 (m, 2H), 2.04 (dtt, J = 14.1, 4.2, 2.8
Hz, 1H), 1.81 (dtt, J = 13.8, 12.6, 3.4 Hz, 1H)；13C{1H} NMR (100
MHz, CDCl3) δ 170.8, 135.6, 135.6, 133.0, 132.7, 128.8, 128.0,
127.5, 127.4, 127.5, 126.0, 125.9, 118.9, 60.4, 57.5, 53.0, 28.5,
28.2, 24.3. The enantiomeric excess was isolated: HPLC Daicel
Chiralpak OD-H column to be 94% with Rt = 9.8 min (major) and
Rt = 11.2 min (minor) [2.0% i-PrOH in hexanes, 1 mL/min, 210
nm, 25 ℃]; [α]25 D +21.7 (c 0.42, CH2Cl2); HRMS (ESI) m/z:
[M+H]+ calcd. for C19H21O2S2 345.0933; found 345.0939.
Compound 3n. Petroleum ether/ethyl acetate (10:1) as the eluent;
colorless oil (32 mg, 93%); 1H NMR (400 MHz, CDCl3) δ 6.51 (d,
J = 2.3 Hz, 2H), 6.46ꟷ6.37 (m, 1H), 6.36 (t, J = 2.3 Hz, 1H),
5.28ꟷ5.17 (m, 2H), 3.98 (d, J = 9.1 Hz, 1H), 3.77 (d, J = 3.7 Hz,
9H), 3.11 (ddd, J = 15.0, 12.6, 2.7 Hz, 2H), 2.75ꟷ2.66 (m, 2H),
2.04ꟷ2.08 (m, 1H), 1.87ꟷ1.77 (m, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 170.7, 160.2, 140.2, 135.4, 118.8, 107.7, 99.3, 60.1, 57.6,
55.2, 53.0, 28.6, 28.3, 24.3; The enantiomeric excess was isolated:
HPLC Daicel Chiralpak OD-H column to be 97% with Rt =11.9
min (major) and Rt = 15.0 min (minor) [2.0% i-PrOH in hexanes,
1 mL/min, 210 nm, 25 ℃]; [α]25 D –16 (c 0.13, CH2Cl2); HRMS
(ESI) m/z: [M+H]+ calcd. for C17H23O4S2 355.1032; found
355.1036.
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Compound 3i. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (25 mg, 71%); 1H NMR (400 MHz, CDCl3)
δ
7.31ꟷ7.25 (m, 4H), 6.47 (ddd, J = 16.9, 10.1, 9.2 Hz, 1H), 5.20 (dd,
J = 16.9, 10.1 Hz, 2H), 4.01 (d, J = 9.2 Hz, 1H), 3.73 (s, 3H),
3.17ꟷ3.03 (m, 2H), 2.70 (dq, J = 13.6, 4.3 Hz, 2H), 2.05 (dtd, J =
13.4, 4.0, 1.9 Hz, 1H), 1.87ꟷ1.77 (m, 1H), 1.29 (s, 9H); 13C{1H}
NMR (100 MHz, CDCl3) δ 170.7, 150.2, 135.8, 134.9, 129.1,
125.0, 118.5, 60.5, 57.2, 52.9, 34.4, 31.3, 28.5, 28.2, 24.3; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak OD-H
column to be 98% with Rt = 6.9 min (minor) and Rt = 7.4 min
(major) [1.0% i-PrOH in hexanes, 1 mL/ min, 210 nm, 25 ℃]; [α]25
D –14.3 (c 0.84, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for
C19H27O2S2 351.1447; found 351.1451.
Compound 3j. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (22 mg, 67%); 1H NMR (400 MHz, CDCl3) δ
7.51ꟷ7.49 (m, 1H), 7.42ꟷ7.41 (m, 1H), 7.20 (dtd, J = 20.1, 7.3, 1.3
Hz, 2H), 6.67 (s, 1H), 6.35 (ddd, J = 17.0, 10.1, 8.9 Hz, 1H), 5.35
(dd, J = 17.0, 10.1 Hz, 2H), 4.39 (d, J = 8.9 Hz, 1H), 3.85 (s, 3H),
3.39ꟷ3.28 (m, 1H), 3.12 (ddd, J = 14.9, 12.6, 2.6 Hz, 1H), 2.74ꟷ2.67
(m, 2H), 2.11ꟷ2.07 (m, 1H), 1.88ꟷ1.78 (m, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 170.7, 154.5, 132.7, 128.1, 123.9, 122.7,
120.9, 120.3, 111.1, 105.8, 57.6, 53.1, 51.5, 28.2, 28.1, 24.2; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak OD-H
column to be 98%with Rt = 9.2 min (major) and Rt = 9.9 min
(minor) [1.0% i-PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25
D +65 (c 0.2, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for
C17H19O3S2 335.0770; found 335.0773.
Compound 3o. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (27 mg, 83%); 1H NMR (600 MHz, CDCl3) δ
7.50ꟷ7.49 (m, 1H), 7.27ꟷ7.22 (m, 1H), 6.93 (t, J = 7.6 Hz, 1H), 6.88
(d, J = 8.2 Hz, 1H), 6.44ꟷ6.34 (m, 1H), 5.15 (dd, J = 16.9, 10.1 Hz,
2H), 4.72 (d, J = 8.6 Hz, 1H), 3.84 (d, J = 1.7 Hz, 3H), 3.72 (d, J =
1.7 Hz, 3H), 3.14 (tt, J = 12.4, 2.3 Hz, 1H), 3.01 (tt, J = 12.4, 2.3
Hz, 1H), 2.73ꟷ2.67 (m, 2H), 2.02 (dtd, J = 13.7, 4.7, 2.1 Hz, 1H),
1.82 (q, J = 13.3 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
170.9, 157.2, 135.8, 130.0, 128.5, 126.8, 120.1, 118.1, 110.7, 61.4,
55.6, 53.0, 48.7, 28.7, 28.3, 24.3; The enantiomeric excess was
isolated: HPLC Daicel Chiralpak OD-H column to be 87% with Rt
= 12.8 min (major) and Rt = 14.2 min (minor) [1.0% i-PrOH in
hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25 D +53.5 (c 0.54,
CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. For C16H21O3S2
325.0927; found 325.0931.
Compound 3k. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (28 mg, 75%); 1H NMR (400 MHz, CDCl3) δ
7.59ꟷ7.52 (m, 4H), 7.44ꟷ7.40 (m, 4H), 7.35ꟷ7.30 (m, 1H), 6.50
(ddd, J = 16.9, 10.1, 8.9 Hz, 1H), 5.24 (dd, J = 16.9, 10.1 Hz, 2H),
4.10 (d, J = 8.9 Hz, 1H), 3.76 (s, 3H), 3.13 (ddd, J = 14.2, 12.5, 2.8
Hz, 2H), 2.75ꟷ2.68 (m, 2H), 2.08ꟷ2.04 (m, 1H), 1.89ꟷ1.78 (m, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 170.7, 140.6, 140.3, 137.1,
135.6, 129.9, 128.7, 127.2, 127.0, 126.7, 118.8, 60.3, 57.2, 53.0,
Compound 3p. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (27 mg, 96%); 1H NMR (400 MHz, CDCl3) δ
7.35ꟷ7.34 (m, 1H), 6.31ꟷ6.20 (m, 3H), 5.31ꟷ5.23 (m, 2H), 4.25 (d,
J = 8.9 Hz, 1H), 3.81 (s, 3H), 3.29 (ddd, J = 14.1, 12.7, 2.9 Hz, 1H),
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3.08 (ddd, J = 14.3, 12.5, 2.7 Hz, 1H), 2.73ꟷ2.61 (m, 2H), 2.09ꟷ2.04
8.3 Hz, 1H), 5.16 (dd, J = 16.9, 10.1, 2H), 3.99 (d, J = 8.3 Hz, 1H),
(m, 1H), 1.86ꟷ1.75 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
170.8, 151.5, 142.0, 133.0, 119.7, 110.2, 108.8, 58.0, 53.0, 51.0,
28.1, 28.1, 24.3; The enantiomeric excess was isolated: HPLC
Daicel Chiralpak OD-H column to be 99% with Rt = 8.2 min
(major) and Rt = 8.6 min (minor) [1.0% i-PrOH in hexanes, 1
mL/min, 210 nm, 25 ℃]; [α]25 D +72.5 (c 0.51, CH2Cl2); HRMS
(ESI) m/z: [M+H]+ calcd. for C13H17O3S2 285.0614; found
285.0616.
Compound 3q. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (28 mg, 95%); 1H NMR (400 MHz, CDCl3) δ 7.22 (d,
J = 5.1 Hz, 1H), 7.01 (d, J = 2.8 Hz, 1H), 6.94 (dd, J = 5.0, 3.7 Hz,
1H), 6.35 (ddd, J = 16.6, 10.1, 8.7 Hz, 1H), 5.20 (d, J = 16.6, 10.1
Hz, 1H), 4.42 (d, J = 8.7 Hz, 1H), 3.80 (s, 3H), 3.19 (ddd, J = 14.0,
12.6, 2.9 Hz, 2H), 2.77ꟷ2.65 (m, 2H), 2.13ꟷ2.04 (m, 1H), 1.89ꟷ1.76
(m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.6, 140.2, 135.5,
127.3, 126.2, 125.2, 118.9, 58.7, 52.8, 52.6, 28.3, 28.1, 24.2; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak OD-H
column to be 99% with Rt = 9.3 min (minor) and Rt = 9.9 min
(major) [2.0% i-PrOH in hexanes, 1 mL/ min, 210 nm, 25 ℃]; [α]25
D +5.9 (c 0.34, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for
C13H17O2S3 301.0385; found 301.0388.
Compound 3r. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (28 mg, 92%); 1H NMR (400 MHz, CDCl3) δ
7.26ꟷ7.21 (m, 2H), 7.10 (dd, J = 5.0, 1.4 Hz, 1H), 6.37 (ddd, J =
16.9, 10.1, 8.7 Hz, 1H), 5.20 (d, J = 16.9, 10.1 Hz, 2H), 4.23 (d, J
= 8.7 Hz, 1H), 3.76 (s, 3H), 3.24ꟷ3.07 (m, 2H), 2.73ꟷ2.67 (m, 2H),
2.10ꟷ2.05 (m, 1H), 1.88ꟷ1.76 (m, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 170.9, 138.2, 135.5, 128.5, 124.8, 123.7, 118.6, 59.4,
52.9, 52.8, 28.4, 28.2, 24.3; The enantiomeric excess was isolated:
HPLC Daicel Chiralpak OD-H column to be 99% with Rt = 8.2 min
(major) and Rt = 8.7 min (minor) [1.0% i-PrOH in hexanes, 1
mL/min, 210 nm, 25 ℃]; [α]25 D +50.0 (c 0.4, CH2Cl2); HRMS
(ESI) m/z: [M+H]+ calcd. for C13H17O2S3 301.0385; found
301.0388.
Compound 3s. Petroleum ether/ethyl acetate (30:1) as the eluent;
colorless oil (22 mg, 75%); 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
J = 2.3 Hz, 1H), 8.51ꟷ8.50 (m, 1H), 7.77 (dt, J = 8.0, 2.0 Hz, 1H),
7.21 (ddd, J = 8.0, 4.8, 0.8 Hz, 1H), 6.40 (ddd, J = 17.0, 10.2, 8.5
Hz, 1H), 5.21 (d, J = 17.0, 10.2 Hz, 1H), 4.08 (d, J = 8.5 Hz, 1H),
3.73 (s, 3H), 3.19ꟷ3.11 (m, 2H), 2.74ꟷ2.66 (m, 2H), 2.03 (dtt, J =
14.2, 4.4, 2.8 Hz, 1H), 1.84ꟷ1.74 (m, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 170.5, 151.0, 148.8, 137.1, 134.7, 133.9, 122.8,
119.6, 59.3, 54.6, 53.0, 28.0, 24.0, 18.4; The enantiomeric excess
was isolated: HPLC Daicel Chiralpak OD-H column to be 96%
with Rt = 21.5 min (major) and Rt = 24.1 min (minor) [5.0% i-
PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25 D +13.7 (c 0.44,
CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for C14H18NO2S2
296.0773; found 296.0778.
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3.30ꟷ3.09 (m, 2H), 2.73ꟷ2.61 (m, 2H), 2.10ꟷ2.01 (m, 1H),
1.87ꟷ1.75 (m, 1H), 1.37 (s, 9H); 13C{1H} NMR (100 MHz ，
CDCl3) δ 168.9, 138.7, 136.4, 129.9, 127.9, 127.3, 118.2, 82.6,
59.9, 57.4, 28.4, 28.0, 27.8, 24.4; The enantiomeric excess was
isolated: HPLC Daicel Chiralpak OD-H column to be 98% with Rt
= 18.3 min (major) and Rt = 20.2 min (minor) [1.0% i-PrOH in
hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25 D –21.7 (c 0.41,
CH2Cl2). HRMS (ESI) m/z: [M+H]+ calcd. for C18H25O2S2
337.1290; found 337.1293.
Compound 3uu. In a 4-dram vial equipped with a magnetic stir bar
were added 3u (24 mg, 0.07 mmol,) and anhydrous THF (2 mL).
After this time, LiAlH4 (3.8 mg, 0.10 mmol, 1.50 equiv) was added
at 0 ℃. The vial was sealed with a cap containing PTFE/silicone
septa. The reaction mixture was stirred at rt for 2 h. The mixture
was quenched with aqueous HCl (1 M, 5 mL) at 0 ℃, and was
stirred at rt for 30 min until all the solids were dissolved. The
mixture was extracted with Et2O (3 x 5 mL). The organic layer was
dried over anhydrous Na2SO4. After removal of solvent under
vacuum, the crude mixture was purified by column
chromatography (EA/PE 1:10). colorless oil (starting from 0.07
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mmol of 3uu; 12.1 mg, 65%). H NMR (400 MHz, CDCl3) δ
7.40ꟷ7.38 (m, 2H), 7.33ꟷ7.26 (m, 3H), 6.52 (dt, J = 16.9, 9.7 Hz,
1H), 5.22ꟷ5.13 (m, 2H), 3.85ꟷ3.77 (m, 2H), 3.59 (d, J = 12.0 Hz,
1H), 2.87 (ddd, J = 14.9, 12.5, 2.8 Hz, 2H), 2.64ꟷ2.55 (m, 2H),
2.08ꟷ2.01 (m, 1H), 1.80 (dtt, J = 13.8, 12.5, 3.4 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 138.5, 136.3, 129.8, 127.9, 127.3,
118.3, 60.8, 58.2, 55.4, 26.0, 25.7, 24.4; The enantiomeric excess
was isolated: HPLC Daicel Chiralpak OD-H column to be 98%
with Rt = 18.3 min (major) and Rt = 20.2 min (minor) [1.0% i-
PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25 D –32.3 (c 0.13,
CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for C14H19OS2
267.0872; found 267.0873.
Compound 3v. Petroleum ether/ethyl acetate (80:1) as the eluent;
colorless oil (28 mg, 76%); 1H NMR (400 MHz, CDCl3) δ
7.35ꟷ7.22 (m, 10H), 6.44 (ddd, J = 16.9, 10.1, 8.8 Hz, 1H), 5.22
(m, 4H), 4.06 (d, J = 8.8 Hz, 1H), 3.05 (ddd, J = 14.2, 12.5, 2.8
Hz, 2H), 2.67ꟷ2.61 (m, 2H), 1.99 (dtt, J = 14.1, 4.3, 2.8 Hz, 1H),
1.79 (dtt, J = 13.7, 12.5, 3.4 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 170.1, 138.1, 135.8, 135.4, 129.7, 128.5, 128.5, 128.4,
128.0, 127.5, 118.7, 67.8, 60.0, 57.4, 28.4, 28.1, 24.2; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak OD-H
column to be 98% with Rt = 18.4 min (major) and Rt = 20.2 min
(minor) [1.0% i-PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25
D –40.1 (c 0.57, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for
C21H23O2S2 371.1134; found 371.1137.
Compound 3vv. In a 4-dram vial equipped with a magnetic stir bar
were added 3v (28 mg, 0.076 mmol,) and anhydrous THF (2 mL).
After this time, LiAlH4 (4.2 mg, 0.110 mmol, 1.50 equiv) was
added at 0 ℃. The vial was sealed with a cap containing
PTFE/silicone septa. The reaction mixture was stirred at rt for 2 h.
The mixture was quenched with aqueous HCl (1 M, 5 mL) at 0 ℃,
and was stirred at rt for 30 min until all the solids were dissolved.
The mixture was extracted with Et2O (3 x 5 mL). The organic layer
was dried over anhydrous Na2SO4. After removal of solvent under
vacuum, the crude mixture was purified by column
chromatography (EA/PE 1:10).
Compound 3t. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (24 mg, 77%); 1H NMR (400 MHz, CDCl3) δ
7.40ꟷ7.38 (m, 2H), 7.32ꟷ7.22 (m, 3H), 6.47 (ddd, J = 16.9, 10.1,
8.7 Hz, 1H), 5.18 (dd, J = 16.9, 10.1 Hz, 2H), 4.18 (qd, J = 6.9, 1.7
Hz, 2H), 4.05 (d, J = 8.7 Hz, 1H), 3.14 (ddd, J = 14.2, 12.6, 2.9 Hz,
2H), 2.75ꟷ2.64 (m, 2H), 2.09ꟷ2.00 (m, 1H), 1.89ꟷ1.75 (m, 1H),
1.25 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.2,
138.3, 135.9, 129.7, 127.9, 127.5, 118.6, 62.2, 59.9, 57.4, 28.5,
28.2, 24.3, 14.1; The enantiomeric excess was isolated: HPLC
Daicel Chiralpak OD-H column to be 99% with Rt = 10.3 min
(major) and Rt = 10.9 min (minor) [1.0% i-PrOH in hexanes, 1
mL/min, 210 nm, 25 ℃]; [α]25 D +6.1 (c 0.33, CH2Cl2). HRMS
(ESI) m/z: [M+H]+ calcd. For C16H21O2S2 309.0977; found
309.0980.
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colorless oil (starting from 0.076 mmol of 3v, 14.3 mg, 71%); H
NMR (400 MHz, CDCl3) δ 7.40ꟷ7.38 (m, 2H), 7.33ꟷ7.26 (m, 3H),
6.52 (dt, J = 16.9, 9.7 Hz, 1H), 5.22ꟷ5.13 (m, 2H), 3.85ꟷ3.77 (m,
2H), 3.59 (d, J = 12.0 Hz, 1H), 2.87 (ddd, J = 14.9, 12.5, 2.8 Hz,
2H), 2.64ꟷ2.55 (m, 2H), 2.08ꟷ2.01 (m, 1H), 1.80 (dtt, J = 13.8,
12.5, 3.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.5, 136.3
129.8, 127.9, 127.3, 118.3, 60.8, 58.2, 55.4, 26.0, 25.7, 24.4; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak OD-H
Compound 3u. Petroleum ether/ethyl acetate (60:1) as the eluent;
colorless oil (24 mg, 73%); 1H NMR (400 MHz, CDCl3) δ
7.44ꟷ7.42 (m, 2H), 7.30ꟷ7.24 (m, 3H), 6.45 (ddd, J = 16.9, 10.1,
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column to be 98% with Rt = 18.4 min (major) and Rt = 20.2 min
15.8, 6.6 Hz, 1H), 4.81 (dd, J = 6.7, 1.3 Hz, 2H), 4.21 (s, 1H), 3.81
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(s, 3H), 3.43 (ddd, J = 14.2, 11.4, 2.7 Hz, 2H), 2.63ꟷ2.57 (m, 2H),
2.18ꟷ1.98 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 169.6,
159.6, 134.5, 128.8, 127.9, 120.0, 114.0, 66.4, 55.2, 39.9, 25.9,
25.0; HRMS (ESI) m/z: [M+H]+ calcd for C15H19O3S2 311.0770;
found 311.0765.
Compound 4d. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.36
g, 93%); 1H NMR (400 MHz, CDCl3) δ 7.24ꟷ7.19 (m, 3H),
7.09ꟷ7.08 (m, 1H), 6.68 (dd, J = 15.9, 1.4 Hz, 1H), 6.29 (dt, J =
15.9, 6.5 Hz, 1H), 4.83 (dd, J = 6.5, 1.3 Hz, 2H), 4.22 (s, 1H), 3.43
(ddd, J = 14.2, 11.5, 2.7 Hz, 2H), 2.64ꟷ2.58 (m, 2H), 2.35 (s, 3H),
2.18ꟷ2.01 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 169.6,
138.1, 136.0, 134.8, 128.9, 128.5, 127.3, 123.8, 122.1, 66.2, 39.9,
25.9, 25.0, 21.3; HRMS (ESI) m/z: [M+H]+ calcd. for C15H19O2S2
295.0821; found 295.0817.
Compound 4e. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.05
g, 96%); 1H NMR (400 MHz, CDCl3) δ 5.85 (dqt, J = 15.5, 6.5, 1.2
Hz, 1H), 5.62 (dtq, J = 14.9, 6.6, 1.7 Hz, 1H), 4.60 (dp, J = 6.6, 1.1
Hz, 2H), 4.18 (s, 1H), 3.42 (ddd, J = 14.2, 11.5, 2.7 Hz, 2H),
2.64ꟷ2.58 (m, 2H), 2.18ꟷ2.01 (m, 2H), 1.74 (dq, J = 6.6, 1.2 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 169.5, 132.0, 124.4, 66.2,
39.9, 25.9, 25.0, 17.8; HRMS (ESI) m/z: [M+H]+ calcd. for
C9H15O2S2 219.0508; found 219.0504.
Compound 4f. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.37
g, 92%); 1H NMR (400 MHz, CDCl3) δ 7.38ꟷ7.34 (m, 2H),
7.04ꟷ6.99 (m, 2H), 6.67 (d, J = 15.8 Hz, 1H), 6.22 (dt, J = 15.9, 6.4
Hz, 1H), 4.82 (d, J = 6.3 Hz, 2H), 4.22 (s, 1H), 3.46ꟷ3.39 (m, 1H),
2.64ꟷ2.58 (m, 1H), 2.19ꟷ1.99 (m, 1H); 13C {1H} NMR (100 MHz,
CDCl3) δ 169.5, 133.5, 128.3, 128.2, 122.2, 115.6, 115.4, 65.9,
39.9, 25.9, 25.0; HRMS (ESI) m/z: [M+Na]+ calcd. for
C14H15FNaO2S2 321.0390; found 321.0393.
Compound 4g. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.49
g, 95%); 1H NMR (400 MHz, CDCl3) δ 7.33ꟷ7.26 (m, 4H), 6.66 (d,
J = 15.9 Hz, 1H), 6.27 (dt, J = 15.9, 6.3 Hz, 1H), 4.82 (dd, J = 6.3,
1.4 Hz, 2H), 4.22 (s, 1H), 3.46ꟷ3.39 (m, 2H), 2.64ꟷ2.59 (m, 2H),
2.18ꟷ2.02 (m, 2H); 13C {1H} NMR (100 MHz, CDCl3) δ 169.5,
134.5, 133.8, 133.2, 128.8, 127.8, 123.1, 65.8, 39.9, 25.9, 25.0;
HRMS (ESI) m/z: [M+Na]+ calcd. for C14H15ClNaO2S2 337.0094;
found 337.0096.
Compound 4h. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.38
g, 93%); 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8.4 Hz, 2H),
7.25 (d, J = 8.5 Hz, 2H), 6.64 (d, J = 15.8 Hz, 1H), 6.29 (dt, J =
15.9, 6.3 Hz, 1H), 4.82 (dd, J = 6.3, 1.4 Hz, 2H), 4.22 (s, 1H), 3.42
(ddd, J = 14.2, 11.5, 2.7 Hz, 2H), 2.64ꟷ2.58 (m, 2H), 2.19ꟷ1.96 (m,
2H); 13C{1H} NMR (100 MHz, CDCl3) δ 169.4, 134.9, 133.2,
131.7, 128.1, 123.2, 122.0, 65.7, 39.8, 25.9, 24.9; HRMS (ESI)
m/z: [M+Na]+ calcd. for C14H15BrNaO2S2 380.9589; found
380.9593.
Compound 4i. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.30
g, 91%); 1H NMR (400 MHz, CDCl3) δ 7.19 (d, J = 5.0 Hz, 1H),
7.01ꟷ6.96 (m, 2H), 6.83 (d, J = 15.7 Hz, 1H), 6.13 (dt, J = 15.7, 6.5
Hz, 1H), 4.79 (dd, J = 6.5, 1.4 Hz, 2H), 4.21 (s, 1H), 3.42 (ddd, J =
14.2, 11.4, 2.7 Hz, 2H), 2.63ꟷ2.58 (m, 2H), 2.23ꟷ1.94 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3) δ 169.5, 141.0, 127.9, 127.4,
126.7, 125.1, 121.8, 65.8, 39.9, 25.9, 25.0; HRMS (ESI) m/z:
[M+Na]+ calcd. for C12H14NaO2S3 309.0048; found 309.0056.
Compound 4j. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.11
g, 90%); 1H NMR (400 MHz, CDCl3) δ 5.82 (dt, J = 15.2, 6.8 Hz,
1H), 5.63ꟷ5.56 (m, 1H), 4.62 (d, J = 6.5 Hz, 2H), 4.18 (s, 1H), 3.42
(minor) [1.0% i-PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25
D –29.6 (c 0.13, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for
C14H19OS2 267.0872; found 267.0873.
Compound 3w. Petroleum ether/ethyl acetate (40:1) as the eluent;
colorless oil (28 mg, 83%); 1H NMR (400 MHz, CDCl3) δ
7.99ꟷ7.97 (m, 2H), 7.48ꟷ7.44(m, 1H), 7.33 (dd, J = 8.4, 7.2 Hz,
2H), 7.17 (tdd, J = 5.3, 3.6, 2.7 Hz, 5H), 6.45 (ddd, J = 17.0, 10.1,
8.0 Hz, 1H), 5.17 (d, J = 10.1, 1H), 4.85 (d, J = 17.0, 1H), 4.24 (d,
J = 8.0 Hz, 1H), 3.29 (ddd, J = 13.9, 12.8, 2.9 Hz, 1H), 3.13 (ddd,
J = 14.1, 12.6, 2.8 Hz, 1H), 2.75ꟷ2.67 (m, 2H), 2.06ꟷ2.01 (m, 1H),
1.89ꟷ1.77 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.5,
138.0, 137.8, 135.8, 131.6, 129.9, 129.8, 127.8, 127.9, 127.3,
118.4, 65.3, 56.9, 28.2, 28.1, 24.0; The enantiomeric excess was
isolated: HPLC Daicel Chiralpak AD-H column to be 94% with Rt
= 8.9 min (major) and Rt = 10.2 min (minor) [1.0% i-PrOH in
hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25 D –40.9 (c 0.22,
CH2Cl2); HRMS (ESI) m/z: [M+H]+calcd. for C20H21OS2
341.1028; found 341.1027.
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Compound 3x. Petroleum ether/ethyl acetate (40:1) as the eluent;
1
White solid: 26 mg, 92%; mp 87ꟷ92 ℃; H NMR (400 MHz,
CDCl3) δ 7.38ꟷ7.36 (m, 2H), 7.33ꟷ7.27 (m, 3H), 6.45 (ddd, J =
16.9, 10.2, 8.1 Hz, 1H), 5.24 (d, J = 10.2, 1H), 5.08 (d, J = 16.9,
1H), 3.85 (d, J = 8.1 Hz, 1H), 3.05ꟷ2.84 (m, 2H), 2.70ꟷ2.59 (m,
2H), 2.32 (d, J = 0.7 Hz, 3H), 2.03ꟷ1.93 (m, 1H), 1.84ꟷ1.68 (m,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 201.2, 137.7, 135.6,
129.5, 128.2, 127.7, 118.5, 67.5, 56.6, 28.0, 27.8, 25.7, 24.1; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak AD-H
column to be 96% with Rt = 9.9 min (minor) and Rt = 11.2 min
(major) [AD-H, 1.0% i-PrOH in hexanes, 1 mL/min, 210 nm, 25
℃]; [α]25 D ꟷ3.9 (c 0.26, CH2Cl2); HRMS (ESI) m/z: [M+H]+
calcd. for C15H19OS2 279.0872; found 279.0873.
General produces for the preparation of compound 4. To a solution of
2-carboxy-1,3-dithiane (0.8 g, 5 mmol) in CH2Cl2 (10 mL) was
added allylic alcohols (0.6 mL, 6 mmol) and DMAP (0.49 g, 4.0
mmol). After cooled to 0 ℃, N, N'- dicyclohexylcarbodiimide
(DCC) (1.15 g, 5.5 mmol) was added portionwise. The reaction
mixture was stirred at 0 ℃ for a few minutes and then warmed to
room temperature. After stirring for 15 h, the reaction mixture was
washed with sat. NH4Cl aq. (×3) and sat. NaHCO3 aq. (×1) and then
dried over Na2SO4. The solvent was removed under reduced
pressure, and the residue was purified by silica gel column
chromatography (hexane/AcOEt = 13/1) to give 4.
Compound 4a. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.32
g, 94%); 1H NMR (400 MHz, CDCl3) δ 7.42ꟷ7.38 (m, 2H),
7.34ꟷ7.31 (m, 2H), 7.28ꟷ7.24 (m, 1H), 6.73ꟷ6.68 (m, 1H), 6.30 (dt,
J = 15.9, 6.4 Hz, 1H), 4.83 (dd, J = 6.4, 1.4 Hz, 2H), 4.22 (s, 1H),
3.43 (ddd, J = 14.2, 11.5, 2.8 Hz, 2H), 2.63ꟷ2.57 (m, 2H), 2.17ꟷ1.98
(m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 169.5, 136.0, 134.6,
128.6, 128.1, 126.6, 122.4, 66.1, 39.8, 25.9, 24.9; HRMS (ESI)
m/z: [M+H]+ calcd for C14H17O2S2 281.0664; found 281.0661.
Compound 4b. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.3
g, 90%); 1H NMR (400 MHz, CDCl3) δ 7.45ꟷ7.42 (m, 1H),
7.19ꟷ7.13 (m, 3H), 6.92 (dt, J = 15.7, 1.4 Hz, 1H), 6.22ꟷ6.15 (m,
1H), 4.86 (dd, J = 6.3, 1.4 Hz, 2H), 4.22 (s, 1H), 3.44 (ddd, J =
14.2, 11.5, 2.7 Hz, 2H), 2.64ꟷ2.58 (m, 2H), 2.35 (s, 3H), 2.16ꟷ1.99
(m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 169.4, 135.6, 135.1,
132.2, 130.2, 127.9, 126.0, 125.7, 123.7, 66.1, 39.8, 25.8, 24.9,
19.7; HRMS (ESI) m/z: [M+H]+ calcd. for C15H19O2S2 295.0821;
found 295.0817.
Compound 4c. Petroleum ether/ethyl acetate (20:1) as the eluent;
colorless oil (starting from 5 mmol of 2-carboxy-1,3-dithiane, 1.26
g, 81%); 1H NMR (400 MHz, CDCl3) δ 7.34ꟷ7.32 (m, 2H),
6.87ꟷ6.85 (m, 2H), 6.65 (dd, J = 15.7, 1.3 Hz, 1H), 6.17 (dt, J =
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The Journal of Organic Chemistry
(ddd, J = 14.2, 11.5, 2.7 Hz, 2H), 2.63ꟷ2.58 (m, 2H), 2.17ꟷ2.03 (m,
126.6, 119.1, 60.1, 57.4, 28.4, 28.2, 24.0, 21.5; The enantiomeric
4H), 1.42 (q, J = 7.4 Hz, 2H), 0.90 (t, J = 7.4 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 169.5, 137.0, 123.2, 66.2, 39.9, 34.2,
25.8, 24.9, 21.9, 13.5; HRMS (ESI) m/z: [M+Na]+ calcd. for C11H18
NaO2S2 269.0640; found 269.0640.
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excess was isolated: HPLC Daicel Chiralpak AD-H column to be
96% with Rt = 6.4 min (major) and Rt = 8.2 min (minor) [10% i-
PrOH in hexanes, 1/1000TFA, 1 mL/min, 210 nm, 25 ℃]; [α]25 D
–10.8 (c 0.37, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for
C15H19O2S2 295.0821; found 295.0818.
Compound 5e. Petroleum ether/ethyl acetate (5:1) as the eluent;
white solid (11.1 mg, 51%); mp 102ꟷ107 ℃; 1H NMR (400 MHz,
CDCl3) δ 6.01 (ddd, J = 17.1, 10.2, 8.4 Hz, 1H), 5.23ꟷ5.14 (m,
2H), 3.24 (ddd, J = 15.4, 12.7, 2.7 Hz, 2H), 2.98ꟷ2.88 (m, 1H),
2.75ꟷ2.70 (m, 2H), 2.17ꟷ2.11 (m, 1H), 1.91ꟷ1.80 (m, 1H), 1.29 (d,
J = 6.9 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 175.6, 137.4,
117.6, 58.6, 45.7, 28.0, 27.9, 24.4, 16.0; The enantiomeric excess
was isolated: HPLC Daicel Chiralpak AD-H column to be 96%
with Rt = 6.6 min (minor) and Rt = 6.9 min (major) [8.0% i-PrOH
in hexanes, 1/1000TFA, 1 mL/ min, 210 nm, 25 ℃]; [α]25 D ꟷ11.8
(c 0.17, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for C9H15O2S2
219.0508; found 219.0509.
Compound 5f. Petroleum ether/ethyl acetate (5:1) as the eluent;
colorless oil (15.2 mg, 51%); 1H NMR (400 MHz, CDCl3) δ 7.39
(dd, J = 8.7, 5.4 Hz, 2H), 6.99 (t, J = 8.7 Hz, 2H), 6.42 (ddd, J =
16.9, 10.2, 8.7 Hz, 1H), 5.29ꟷ5.17 (m, 2H), 4.06 (d, J = 8.7 Hz,
1H), 3.18ꟷ3.11 (m, 2H), 2.75ꟷ2.69 (m, 2H), 2.12ꟷ2.06 (m, 1H),
1.86ꟷ 1.77 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 175.6,
135.0, 133.4, 131.5, 119.4, 115.1, 114.8, 59.5, 56.3, 28.3, 28.1,
23.9; The enantiomeric excess was isolated: HPLC Daicel
Chiralpak AD-H column to be 97% with Rt = 8.9 min (major) and
Rt = 10.9 min (minor) [8.0% i-PrOH in hexanes, 1/1000TFA, 1
mL/ min, 210 nm, 25 ℃]; [α]25 D ꟷ54.12 (c 0.85, CH2Cl2); 19F
NMR (282 MHz, CDCl3): δ ꟷ114.6; HRMS (ESI) m/z: [M+Na]+
calcd. for C14H15FNaO2S2 321.0390; found 321.0393.
General produces for the preparation of compound 5. In a reaction
vessel [Ir(cod)Cl]2 (0.002 mmol), chiral phosphoramidite (0.004
mmol), and TBD (0.01 mmol) were dissolved in THF (0.5 mL)
under Ar atmosphere. The reaction vessel was sealed with a screw
cap and the mixture heated at 50 ℃ (oil bath) for 30 min to allow
the formation of the active catalyst species (the solution turns from
orange to yellow). After this time, K3PO4 (0.15 mmol) and 4 (0.1
mmol) were added and the resulting mixture was heated at 50 ℃
(oil bath). Upon completion, the reaction was then quenched by 1N
HCl and diluted with ethyl acetate. The organic phases were
separated and the aqueous phase was extracted with ethyl acetate
(3x). The combined organic phase was dried over Na2SO4, filtered
and concentrated under vacuum. The mixture was then purified by
flash chromatography affording the product.
Compound 5a. Petroleum ether/ethyl acetate (5:1) as the eluent;
colorless oil (17 mg, 62%); 1H NMR (400 MHz, CDCl3) δ
7.41ꟷ7.39 (m, 2H), 7.30ꟷ7.26 (m, 3H), 6.46 (ddd, J = 16.9, 10.1,
9.0 Hz, 1H), 5.25 (dd, J = 16.9, 10.1 Hz, 2H), 4.05 (d, J = 9.0 Hz,
1H), 3.13 (ddd, J = 15.2, 12.7, 2.9 Hz, 2H), 2.75ꟷ2.68 (m, 2H), 2.07
(ddt, J = 11.2, 4.2, 2.7 Hz, 1H), 1.82 (qt, J = 12.7, 3.4 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 174.3, 137.7, 135.2, 129.8,
128.1, 127.8, 119.2, 60.4, 57.4, 28.5, 28.2, 24.1; The enantiomeric
excess was isolated: HPLC Daicel Chiralpak AD-H column to be
98% with Rt = 6.0 min (major) and Rt = 7.5 min (minor) [15% i-
PrOH in hexanes, 1/1000TFA, 1 mL/min, 210 nm, 25 ℃]; [α]25 D
ꟷ8.3 (c 0.24, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for
C14H17O2S2 281.0664; found 281.0667.
Compound 5b. Petroleum ether/ethyl acetate (5:1) as the eluent;
colorless oil (16.7 mg, 57%); 1H NMR (400 MHz, CDCl3) δ
7.66ꟷ7.64(m, 1H), 7.18ꟷ7.16 (m, 3H), 6.31 (ddd, J = 16.9, 10.1, 8.1
Hz, 1H), 5.21 (d, J = 10.1, 1H), 5.09 (d, J = 16.9, 1H), 4.37 (d, J =
8.1 Hz, 1H), 3.15 (ddd, J = 14.9, 12.8, 2.8 Hz, 2H), 2.75ꟷ2.69 (m,
2H), 2.42 (s, 3H), 2.11ꟷ2.05 (m, 1H), 1.91ꟷ1.80 (m, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 173.5, 137.1, 136.4, 135.5, 130.6,
128.5, 127.4, 125.9, 118.7, 61.3, 52.6, 28.7, 28.2, 24.0, 20.4; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak AD-H
column to be 99% with Rt = 9.5 min (major) and Rt = 10.0 min
(minor) [15% i-PrOH in hexanes, 1/1000TFA, 1 mL/min, 210 nm,
25 ℃]; [α]25 D ꟷ15.8 (c 0.38, CH2Cl2); HRMS (ESI) m/z: [M+H]+
calcd. for C15H19O2S2 295.0821; found 295.0818.
Compound 5c. Petroleum ether/ethyl acetate (5:1) as the eluent;
colorless oil (17 mg, 55%); 1H NMR (400 MHz, CDCl3) δ
7.34ꟷ7.30 (m, 2H), 6.85ꟷ6.83 (m, 2H), 6.44 (ddd, J = 16.9, 10.1,
8.9 Hz, 1H), 5.22 (dd, J = 16.9 Hz, 10.1 Hz, 2H), 4.02 (d, J = 8.9
Hz, 1H), 3.78 (s, 3H), 3.13 (ddd, J = 14.9, 12.6, 2.7 Hz, 2H),
2.77ꟷ2.65 (m, 2H), 2.08 (dtt, J = 14.0, 4.6, 2.8 Hz, 1H), 1.88ꟷ1.76
(m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 175.1, 159.0, 135.4,
130.8, 129.6, 118.9, 113.5, 60.2, 56.6, 55.1, 28.4, 28.2, 24.1; The
enantiomeric excess was isolated: HPLC Daicel Chiralpak AD-H
column to be 85% with Rt =12.8 min (major) and Rt = 13.9 min
(minor) [10% i-PrOH in hexanes, 1/1000TFA, 1 mL/min, 210 nm,
25 ℃]; [α]25 Dꟷ11.1 (c 0.18, CH2Cl2); HRMS (ESI) m/z: [M+H]+
calcd. for C15H19O3S2 311.0770; found 311.0768.
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Compound 5g. Petroleum ether/ethyl acetate (5:1) as the eluent;
colorless oil (16.9 mg, 54%); 1H NMR (400 MHz, CDCl3) δ
7.37ꟷ7.35 (m, 2H), 7.29ꟷ7.26 (m, 2H), 6.41 (ddd, J = 16.9, 10.2,
8.7 Hz, 1H), 5.32ꟷ5.13 (m, 2H), 4.05 (d, J = 8.7 Hz, 1H), 3.15 (ddd,
J = 14.3, 12.7, 2.8 Hz, 2H), 2.75ꟷ2.69 (m, 2H), 2.12ꟷ2.05 (m, 1H),
1.86ꟷ1.76 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 175.2,
136.2, 134.8, 133.7, 131.2, 128.2, 119.6, 59.3, 56.5, 28.3, 28.1,
23.9; The enantiomeric excess was isolated: HPLC Daicel
Chiralpak AD-H column to be 98% with Rt = 10.2 min (major) and
Rt = 11.9 min (minor) [8.0% i-PrOH in hexanes, 1/1000TFA, 1
mL/ min, 210 nm, 25 ℃]; [α]25 D ꟷ46.67 (c 0.9, CH2Cl2); HRMS
(ESI) m/z: [M+Na]+ calcd. for C14H15ClNaO2S2 337.0094; found
337.0096.
Compound 5h. Petroleum ether/ethyl acetate (5:1) as the eluent;
colorless oil (19.7 mg, 55%); 1H NMR (400 MHz, CDCl3) δ
7.44ꟷ7.42 (m, 2H), 7.31ꟷ7.26 (m, 2H), 6.41 (ddd, J = 16.9, 10.1,
8.7 Hz, 1H), 5.29ꟷ5.17 (m, 2H), 4.03 (d, J = 8.7 Hz, 1H), 3.15 (ddd,
J = 14.3, 12.6, 2.7 Hz, 2H), 2.76ꟷ2.68 (m, 2H), 2.12ꟷ2.06 (m, 1H),
1.87ꟷ1.75 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 175.0,
136.7, 134.7, 131.6, 131.2, 121.9, 119.6, 59.3, 56.5, 28.3, 28.1,
23.9; The enantiomeric excess was isolated: HPLC Daicel
Chiralpak AD-H column to be 97% with Rt = 10.8 min (major) and
Rt = 12.7 min (minor) [8.0% i-PrOH in hexanes, 1/1000TFA, 1 mL/
min, 210 nm, 25 ℃]; [α]25 D ꟷ50 (c 0.5, CH2Cl2); HRMS (ESI)
m/z: [M+Na]+ calcd. for C14H15BrNaO2S2 380.9589; found
380.9593.
Compound 5i. Petroleum ether/ethyl acetate (5:1) as the eluent;
colorless oil (17.2 mg, 60%); 1H NMR (400 MHz, CDCl3) δ 7.25
(dd, J = 5.1, 1.2 Hz, 1H), 7.07ꟷ7.05 (m, 1H), 6.96 (dd, J = 5.2, 3.5
Hz, 1H), 6.35 (ddd, J = 16.9, 10.1, 8.7 Hz, 1H), 5.30ꟷ5.24 (m, 2H),
4.44 (d, J = 8.7 Hz, 1H), 3.30ꟷ3.19 (m, 2H), 2.75ꟷ2.68 (m, 2H),
2.13ꟷ2.09 (m, 1H), 1.87ꟷ1.78 (m, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 176.3, 139.8, 135.2, 127.6, 126.2, 125.4, 119.3, 57.8,
Compound 5d. Petroleum ether/ethyl acetate (5:1) as the eluent;
colorless oil (17.3 mg, 59%); 1H NMR (400 MHz, CDCl3) δ
7.20ꟷ7.17 (m, 3H), 7.09ꟷ7.07 (m, 1H), 6.45 (ddd, J = 16.8, 10.1,
9.1 Hz, 1H), 5.24 (d, J = 16.8, 10.1 Hz, 1H), 4.02 (d, J = 9.1 Hz,
1H), 3.21ꟷ3.07 (m, 2H), 2.77ꟷ2.66 (m, 2H), 2.33 (s, 3H), 2.08 (dtd,
J = 14.0, 4.3, 2.2 Hz, 1H), 1.88ꟷ1.77 (m, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 175.0, 137.7, 137.5, 135.3, 130.5, 128.5, 128.0,
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52.5, 28.2, 28.0, 23.9; The enantiomeric excess was isolated: HPLC
colorless oil (16.8 mg, 57%); 1H NMR (400 MHz, CDCl3) δ
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Daicel Chiralpak AD-H column to be 98% with Rt = 14.2 min
(major) and Rt = 15.1 min (minor) [8.0% i-PrOH in hexanes,
1/1000TFA, 1 mL/ min, 210 nm, 25 ℃]; [α]25 D ꟷ38 (c 0.5,
CH2Cl2);
7.36ꟷ7.26 (m, 5H), 3.71 (s, 3H), 3.21ꟷ3.02 (m, 3H), 2.74ꟷ2.62 (m,
2H), 2.12ꟷ1.99 (m, 3H), 1.79 (dtt, J = 13.9, 12.6, 3.4 Hz, 1H), 0.73
(t, J = 7.3 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 171.2,
138.0, 130.0, 127.8, 127.5, 61.9, 55.7, 52.9, 28.7, 28.2, 24.5, 24.0,
12.7; The enantiomeric excess was isolated: HPLC Daicel
Chiralpak AD-H column to be 98% with Rt = 6.5 min (major) and
Rt = 7.6 min (minor) [1.0% i-PrOH in hexanes, 1 mL/ min, 210 nm,
25 ℃]; [α]25 D ꟷ4.5 (c 0.2, CH2Cl2); HRMS (ESI) m/z: [M+H]+
calcd. for C15H21O2S2 297.0977; found 297.0982.
Compound 5a. A 1-dram vial containing a magnetic stir bar was
charged with 3a (29.4 mg, 0.1 mmol, 1.0 equiv), NaOH (8 M
aqueous solution, 0.24 mL, 1.92 mmol, 20 equiv), and MeOH (0.5
mL). The vial was sealed with a cap containing PTFE/silicone
septa. The reaction mixture was stirred at 80 ℃ (oil bath) for 6 h.
The mixture was acidified with aqueous HCl solution (1 M, 5 mL)
and the resulting mixture was extracted with Et2O (3 x 5 mL). The
organic layer was dried over anhydrous Na2SO4. After removal of
solvent under vacuum, the title compound was obtained without
further purification.
HRMS (ESI) m/z: [M+Na]+ calcd. for C12H14NaO2S3 309.0048;
found 309.0054.
Compound 5j. Petroleum ether/ethyl acetate (5:1) as the eluent;
colorless oil (16.5 mg, 67%); 1H NMR (400 MHz, CDCl3) δ
5.87ꟷ5.78 (m, 1H), 5.24ꟷ5.15 (m, 2H), 3.32ꟷ3.18 (m, 2H),
2.74ꟷ2.64 (m, 3H), 2.15ꟷ2.11 (m, 1H), 1.92ꟷ1.81 (m, 1H),
1.70ꟷ1.64 (m, 1H), 1.56ꟷ1.38 (m, 2H), 1.25ꟷ1.18 (m, 1H), 0.90 (t,
J = 7.3 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 175.8, 135.8,
119.5, 58.7, 51.9, 31.9, 28.0, 24.5, 20.7, 13.7; The enantiomeric
excess was isolated: HPLC Daicel Chiralpak AD-H column to be
91% with Rt = 7.1 min (minor) and Rt = 7.7 min (major) [8.0% i-
PrOH in hexanes, 1/1000TFA, 1 mL/ min, 210 nm, 25 ℃]; [α]25 D
+5 (c 0.2, CH2Cl2); HRMS (ESI) m/z: [M+Na]+ calcd. for
C11H18NaO2S2 269.0640; found 269.0647.
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Compound 6. To a solution of 3k (74 mg, 0.2 mmol) in absolute
MeOH (10 mL), Raney-nickel (1 g, Aldrich- 2800 50% slurry in
water) was added. The reaction mixture was stirred at 50 ℃ (oil
bath) for 12 h, then was filtered through a Celite pad and washed
with absolute THF. The organic solution was dried over MgSO4
and concentrated in vacuum to afford a crude residue that was
purified by flash column chromatography (EA/PE 1:40) to give the
colorless oil compound 6 (50 mg, 93% yield).
colorless oil (28 mg, 99%); 1H NMR (400 MHz, CDCl3) δ
7.41ꟷ7.39 (m, 2H), 7.30ꟷ7.26 (m, 3H), 6.46 (ddd, J = 16.9, 10.1,
9.0 Hz, 1H), 5.25 (dd, J = 16.9, 10.1 Hz, 1H), 4.05 (d, J = 9.0 Hz,
1H), 3.13 (ddd, J = 15.2, 12.7, 2.9 Hz, 2H), 2.75ꟷ2.68 (m, 2H), 2.07
(ddt, J = 11.2, 4.2, 2.7 Hz, 1H), 1.82 (qt, J = 12.7, 3.4 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 174.3, 137.7, 135.2, 129.8,
128.1, 127.8, 119.2, 60.4, 57.4, 28.5, 28.2, 24.1; The enantiomeric
excess was isolated: HPLC Daicel Chiralpak AD-H column to be
98% with Rt = 6.0 min (major) and Rt = 7.5 min (minor) [15% i-
PrOH in hexanes, 1 mL/ min, 210 nm, 25 ℃]; [α]25 D ꟷ8.3 (c 0.24,
CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for C14H17O2S2
281.0664; found 281.0667.
Compound 10. A 1-dram vial containing a magnetic stir bar was
charged with carboxylic acid 5a (28 mg, 0.1 mmol, 1.0 equiv),
sodium bicarbonate (NaHCO3, 11.8 mg, 0.14 mmol, 1.4 equiv),
acetonitrile (1.0 mL), and water (1.0 mL). The mixture was stirred
at rt until the carboxylic acid was completely dissolved. After this
time, potassium iodide (KI, 21.6 mg, 0.130 mmol, 1.30 equiv) and
iodine (I2, 33.0 mg, 0.13 mmol, 1.3 equiv) were added into the
mixture. The reaction mixture was stirred at rt for 2 h. The reaction
mixture was quenched with a saturated aqueous sodium thiosulfate
(Na2SO4) solution dropwise until the yellow color disappeared.
After this time, 5 mL of water was added into the mixture. The
mixture was extracted with EtOAc (3 x 5 mL). The organic layer
was dried over anhydrous Na2SO4. After removal of solvent under
vacuum, the crude mixture was purified by column
chromatography (EA/PE 1:10).
colorless oil (50 mg, 93%); 1H NMR (400 MHz, CDCl3) δ
7.60ꟷ7.58 (m, 2H), 7.54ꟷ7.52 (m, 2H), 7.42 (dd, J = 8.4, 6.9 Hz,
2H), 7.34ꟷ7.30 (m, 1H), 7.26ꟷ7.24 (m, 2H), 3.60 (s, 3H), 3.06 (qd,
J = 7.9, 5.5 Hz, 1H), 2.71ꟷ2.58 (m, 2H), 1.77ꟷ1.58 (m, 2H), 0.83
(t, J = 7.3 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 173.0,
143.0, 140.9, 139.2, 128.7, 127.9, 127.1, 127.1, 126.9, 51.5, 43.5,
41.2, 29.1, 11.9; The enantiomeric excess was isolated: HPLC
Daicel Chiralpak AD-H column to be >99% with Rt = 11.2 min
(major) and Rt = 11.5 min (minor) [0.5% i-PrOH in hexanes, 1
mL/min, 210 nm, 25 ℃]; [α]25 D ꟷ2.8 (c 0.36, CH2Cl2); HRMS
(ESI) m/z: [M+H]+ calcd. for C18H21O2 269.1536; found 269.1540.
Compound 7. To a solution of 3k (74 mg, 0.2 mmol) in absolute THF
(10 mL), Raney-nickel (1 g, Aldrich-2800 50% slurry in water) was
added. The reaction mixture was stirred at 50 ℃ (oil bath) for 12 h,
then was filtered through a Celite pad and washed with absolute
MeOH. The organic solution was dried over MgSO4 and
concentrated in vacuum to afford a crude residue that was purified
by flash column chromatography (EA/PE 1:40) to give the
colorless oil compound (51 mg, 95% yield).
colorless oil (33.8 mg, 83%); 1H NMR (400 MHz, CDCl3) δ
7.40ꟷ7.31 (m, 3H), 7.23ꟷ7.21 (m, 2H), 5.30 (ddd, J = 8.9, 6.1, 5.1
Hz, 1H), 3.88 (ddd, J = 13.9, 13.1, 2.7 Hz, 1H), 3.69 (d, J = 5.1 Hz,
1H), 3.34ꟷ3.26 (m, 2H), 2.82ꟷ2.72 (m, 2H), 2.56ꟷ2.51 (m, 1H),
2.22ꟷ2.15 (m, 1H), 1.88 (dtt, J = 14.0, 12.9, 3.1 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 172.5, 130.4, 130.2, 129.0, 128.3, 79.6，
58.1, 52.1, 27.2, 27.1, 24.5, 0.1; The enantiomeric excess was
isolated: HPLC Daicel Chiralpak OD-H column to be 99% with Rt
= 14.8 min (major) and Rt = 16.1 min (minor) [2.0% i-PrOH in
hexanes, 1 mL/min, 210 nm, 25 ℃]; [α]25 D +31.5 (c 0.24,
CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd. for C14H16IO2S2
406.9631; found 406.9635.
colorless oil (51 mg, 95%); 1H NMR (400 MHz, CDCl3) δ
7.58ꟷ7.53 (m, 4H), 7.42 (dd, J = 8.4, 6.9 Hz, 2H), 7.35ꟷ7.28 (m,
3H), 6.01 (ddd, J = 17.3, 10.5, 7.2 Hz, 1H), 5.11 (dd, J = 17.3, 10.5
Hz, 2H), 3.92 (q, J = 7.2 Hz, 1H), 3.64 (s, 3H), 2.84ꟷ2.72 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 172.3, 141.5, 140.8, 140.1,
139.6, 128.7, 127.9, 127.3, 127.2, 127.0, 115.0, 51.6, 45.2, 40.0;
The enantiomeric excess was isolated: HPLC Daicel Chiralpak
AD-H column to be 99% with Rt = 8.9 min (major) and Rt = 9.5
min (minor) [1.0% i-PrOH in hexanes, 1 mL/min, 210 nm, 25 ℃];
[α]25 D ꟷ2.4 (c 0.84, CH2Cl2); HRMS (ESI) m/z: [M+H]+ calcd.
for C18H19O2 267.1380; found 267.1382.
Compound 8. To a solution of substrate 3a in degassed solvent (THF,
0.2 M) and saturated by hydrogen was added 10% Wilkinson’s
catalyst. The solution was stirred under a hydrogen atmosphere at
room temperature. When the hydrogenation was deemed complete
by TLC, the reaction mixture was filtered through a short pad of
alumina and washed thoroughly with diethyl ether. Purification by
flash chromatography (EA/PE 1:50) on silica gel provided the
saturated product 8.
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The Journal of Organic Chemistry
Y.; Zeng, X.-Y.; Zheng, Y.; Wei, K.; Yang, Y.-R. Ir-Catalyzed
Asymmetric Total Synthesis of (ꟷ)-Communesin F. J. Am. Chem.
Soc. 2017, 139, 3364ꟷ3367.
ASSOCIATED CONTENT
1
Supporting Information
2
3
4
5
6
7
8
9
5. For selected our works on 1,3-dithiane, see: (a) Liang, Y.; Lai, J.;
Liu, T.; Tang, S. Direct Regioselective [3 + 2]-Cyclization
Reactions of Ambivalent Electrophilic/Nucleophilic β-
Chlorovinyl Dithianes: Access to Cyclopentene Derivatives. Org.
Lett. 2016, 18, 5086-5089. (b) Xing, Z.; Yang, M.; Sun, H.; Wang,
Z.; Chen, P.; Liu, L.; Wang, X.; Xie, X.; She, X. Visible-light
promoted dithioacetalization of aldehydes with thiols under
aerobic and photocatalyst-free conditions. Green Chem. 2018, 20,
5117ꟷ5122. (c) Wang, X.; Wang, W.; Zheng, H.; Su, Y.; Jiang,
T.; He, Y.; She, X. Efficient Asymmetric Total Syntheses of
Cryptocarya Triacetate, Cryptocaryolone, and Cryptocaryolone
Diacetate. Org. Lett. 2009, 11, 3136ꟷ3138. (d) Trong, N.; Li, M.;
Pascual, A.; Yucel, B.; Walsh, P. J. Palladium-Catalyzed Allylic
Alkylation of 2-1,3-Dithianes, an Umpolung Synthesis of β,γ-
Unsaturated Ketones. Adv. Syn. Catal. 2019, 361, 502ꟷ509. (e)
Smith, A. B.; Adam, C. M. Evolution of Dithiane-Based
Strategies for the Construction of Architecturally Complex
Natural Products. Acc. Chem. Res. 2004, 37, 365ꟷ377.
The Supporting Information is available free of charge on the ACS
Publications website at DOI:.
Experimental procedures, characterization data, NMR spectra, and
X-ray analysis (PDF)
AUTHOR INFORMATION
Corresponding Author
E-mail: wangpp17@lzu.edu.cn
E-mail: jiangq18@lzu.edu.cn
E-mail: zhaorb18@lzu.edu.cn
E-mail: xiexg@lzu.edu.cn
E-mail: tangshch@lzu.edu.cn
E-mail: wangxiaolei@lzu.edu.cn
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENT
6. (a) Kondol, A.; Oishi, M.; Takeda, T.; Terada, M.
Enantioselective Addition of a 2-Alkoxycarbonyl-1,3-dithiane to
This work was supported by the National Science Foundation of
China (051170001, 21772074), the Fundamental Research Funds
for the Central Universities (lzujbky-2017-k06) and X.W. thanks
the Thousand Young Talents Program for financial support.
Imines Catalyzed by
a
Bis(guanidino)iminophosphorane
Organosuperbase. Angew. Chem., Int. Ed. 2015, 54, 15836ꟷ15839.
(b) Yao, K.; Liu, D.; Yuan, Q.; Imamoto, T.; Liu, Y.; Zhang, W.
1,3-Dithianes as Acyl Anion Equivalents in Pd-Catalyzed
Asymmetric Allylic Substitution. Org. Lett. 2016, 18, 6296ꟷ6299.
(c) Massolo, E.; Benaglia, M.; Genoni, A.; Annunziata, R.;
Celentano, G.; Gaggero, N. Stereoselective reaction of 2-
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