Synthesis of γ-sulfonyl δ-lactones and β-sulfonyl styrenes

Article abstract of DOI:10.1016/j.tet.2016.11.051

A facile route to the synthesis of γ-sulfonyl lactones 5 and β-sulfonyl styrenes 6 has been developed, achieving moderate to good yields via the (1) NaH mediated Michael addition of β-ketosulfones 3 and methyl acrylate in refluxing THF and (2) NaBH₄mediated stereoselective reduction/lactonization of δ-ketoesters 4 in boiling MeOH, or (3) boron trifluoride etherate mediated ring-opening of lactones 5 in MeOH at reflux.

Full text of DOI:10.1016/j.tet.2016.11.051

Accepted Manuscript
Synthesis of γ-sulfonyl δ-lactones and β-sulfonyl styrenes
Chieh-Kai Chan, Yu-Hsin Chen, Ru-Ting Hsu, Meng-Yang Chang
PII:
S0040-4020(16)31215-7
10.1016/j.tet.2016.11.051
TET 28265
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 17 October 2016
Revised Date: 10 November 2016
Accepted Date: 19 November 2016
Please cite this article as: Chan C-K, Chen Y-H, Hsu R-T, Chang M-Y, Synthesis of γ-sulfonyl δ-lactones
and β-sulfonyl styrenes, Tetrahedron (2016), doi: 10.1016/j.tet.2016.11.051.
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Synthesis of γ-Sulfonyl δ-Lactones and β-Sulfonyl Styrenes
Chieh-Kai Chan,a Yu-Hsin Chen,a Ru-Ting Hsu*,b and Meng-Yang Chang*,a
aDepartment of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
bDepartment of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, 82144, Taiwan
Michael addition
reductive lactonization
O
ring-opening
BF , MeOH
CO Me
2
CO Me
2
NaH, THF
NaBH , MeOH
4
3
O
S
O
S
O
S
O
S
1
1
1
1
O
Ar
O
Ar
O
Ar
Ar
Ar
methyl acrylate
Ar
O
Ar
O
Ar
O
O
3
4
5
6

ACCEPTED MANUSCRIPT
Tetrahedron
1
TETRAHEDRON
Pergamon
Synthesis of γ-Sulfonyl δ-Lactones and β-Sulfonyl Styrenes
Chieh-Kai Chan,a Yu-Hsin Chen,a Ru-Ting Hsu*,b and Meng-Yang Chang*,a
aDepartment of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan bDepartment of
Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, 82144, Taiwan
Abstract — A facile route to the synthesis of γ-sulfonyl lactones 5 and β-sulfonyl styrenes 6 has been developed, achieving
moderate to good yields via the (1) NaH mediated Michael addition of β-ketosulfones 3 and methyl acrylate in refluxing THF
and (2) NaBH4 mediated stereoselective reduction/lactonization of δ-ketoesters 4 in boiling MeOH, or (3) boron trifluoride
etherate mediated ring-opening of lactones 5 in MeOH at reflux.
Scheme 1. Synthesis of γ-sulfonyl lactones 5 and β-
sulfonyl styrenes 6
1. Introduction
CO Me
2
CO Me
2
The sulfonyl group, a key core substituent, is known to
act as a highly reactive moiety in the synthetic and
biological arenas. 1 -2 Sulfonyls are useful functionalized
building blocks for the construction of diversified structural
frameworks. These important skeletons having a sulfonyl
component include acyclic skeletons (diketone,3 α-
methenyl ketone,4 styrylsulfone5 and cyclic sulfone),6
cyclic skeletons (vinylcyclopropane,7 triazole,8 pyrazole,9
dihydrofuran,10 diaryltetrahydrofuran,11 tetrahydropyran,12
arylpyrrole,13 vinylfuran,14 arene,15 and pyridazine),16 and
benzofused skeletons (benzosuberan,17 naphthalene,18
tetralin,19 phenanthrene,20 phenanthrofuran,21 lactone22-23
and styrene).24 Despite a number of successful reports on
the synthetic applications of this sulfonyl unit, finding a
new methodology with a high level of chemical control is
still demanded. Due to the importance of such sulfonyl
substituents, the development of a new protocol for the
formation of sulfonyl skeletons with a broad substrate
scope is still highly desirable. In continuation of our
investigation into the applications of β-ketosulfones, we
introduce β-ketosulfones 3 (prepared from substituted 2-
bromoacetophenones 1 and sodium arenesulfinates 2) as
the starting material for synthesizing skeletons of sulfonyl
lactones and styrenes. As shown in Scheme 1, the synthesis
of γ-sulfonyl δ-lactones 5 with a 5-aryl motif and sulfonyl
styrenes 6 having an α-ethylene ester group is well
developed, and includes the (1) NaH mediated Michael
addition of β-ketosulfones 3 and methyl acrylate in THF, (2)
NaBH4 mediated stereoselective lactonization of δ-
ketoesters 4 in MeOH and (3) boron trifluoride etherate
mediated ring-opening of lactones 5 in MeOH.
O
O
S
O
S
O
S
O
S
1
1
1
1
O
Ar
Ar
Ar
O
Ar
O
Ar
Ar
O
O
Ar
O
Ar
O
6
5
4
3
Notably, few reports have been presented for generating
sulfonyl lactones. For example, Thompson developed the
remote dianions promoted annulation of γ-sulfonyl esters
with arylaldehydes.22 In contrast to sulfonyl lactones, a
number of synthetic reports have documented the routes of
sufonyl styrenes.24 Various catalysts or reagents initiating
the synthesis of sufonyl styrenes were summarized using
transition metals (Fe/Cu, Pd2+, Cu2+, Ru2+),24 oxidants
(PhI(OAc)2, I2/TBHP),25 electrolysis,26 photolysis,27 and
other acids or bases.28 However, the new synthetic designs
of sulfone-based lactones and styrenes still suggest a
continuing need in the organic field, especially for those
that allow a one-step facile operation.
2. Results and discussion
First, β-ketosulfone 3a (Ar = Ph, Ar1 = Tol) and methyl
acrylate were chosen as the model’s substrates for base
mediated Michael addition. However, attempts with some
base/solvent
systems
(K2CO3/acetone,
DBU/THF,
tBuOK/THF, DABCO/CH2Cl2) failed at reflux conditions
and only the starting material 3a was recovered. After
changing the system to NaH/THF, 85% of 4a was isolated,
as shown in Table 1. In the next step, δ-ketoester 4a was
treated with 3.0 equivalents of NaBH4 in MeOH for 20 h
resulting in lactone 5a at an 86% yields via the
stereochemical reduction (via the Felkin─Anh model A1)29
followed by sequential cyclization of in situ forming boron-
chelated δ-hydroxy ester A2 (Scheme 2). For
———
Keywords: β-Ketosulfones; Lactones; Styrenes.
*Corresponding author. Tel.: +886 7 3121101 ext 2220
e-mail: ruting@ms.szmc.edu.tw, mychang@kmu.edu.tw

ACCEPTED MANUSCRIPT
2
Tetrahedron
stereoselective reduction of α-functionalized β-ketosulfone,
a similar result has been described in our previous reports.19
Under refluxing MeOH conditions, ring-closure of in situ
generating δ-hydroxy ester gave to produce 5a. On the
basis of the above two steps, the skeleton of δ-lactone
having a cis-configured orientation between δ-phenyl and
γ-sulfonyl groups, was established at an overall yield of
73%. Furthermore, treatment of 5a with a solution of boron
trifluoride etherate in MeOH provided sulfonyl styrene 6a
in a 76% yield via the lactone ring-opening. For the
formation of 6a, the initial pathway should be that boron
trifluoride etherate chelated the oxygen atom of the lactone
to lead to B. Next, MeOH promoted the ring-opening to
give the BF3-chelated hydroxyl moiety. Following the
substituent of 3, the diversified electron-neutral, weaker
electron-withdrawing (for 3c) and electron-donating aryl
groups were well tolerated. 4a-d and 4g-m were isolated at
a range of 78%-85% and 70%-83% yields. However, the
condition was inappropriate for stronger electron-
withdrawing groups. 3e, having a 4-trifluoromethylphenyl
group, gave only 45% of 4e. 3f, with a 4-nitrophenyl group,
could not provide 4f, and a complex mixture was observed.
For the synthesis of 5, 5a-d and 5g-m having high d.e. (>
95%) were obtained in moderate to good yields (69%-86%)
by the stated conditions. For the Ar and Ar1 substituents of
5, the electron-neutral and electron-donating aryl groups
produced 6a-d and 6g-m at a range of 62%-76% yields.
elimination by BF3, in situ formed
C
underwent
Scheme 2. Plausible mechanism
dehydration to afford a 6a having an (E)-configured
conformation (Scheme 2).
Tol
CO Me
2
O
O
S
Ph
O
MeO C
NaBH
Table 1. Synthesis of 6a-c
2
4
O
O
S
H
O
Tol
O
O
MeO
H
MeOH
reflux
20h
H B
S
H
3
Tol
B
H
H
Ph
4a
O
CO Me
2
CO Me
2
Ph
A2
O
H
H
NaH, THF
reflux, 20h
O
A1
NaBH
BF
3
4
O
S
O
S
O
S
3
1
1
1
O
Ar
O
Ar
Ar
Ar
CO Me
2
reflux
MeOH
reflux
20 h
MeOH
reflux
20 h
CO Me
MeOH
O
CO Me
2
2
Ar
O
Ar
O
O
O
F B
3
4
5
6
BF
H
3
H
H
O
S
O
O
O
entry 3, Ar =, Ar1 =
4 (%)d 5 (%)d,e 6 (%)d
4a, 85 5a, 86 6a, 76
4b, 86 5b, 82 6b, 75
4c, 78 5c, 78 6c, 70
4d, 80 5d, 73 6d, 68
Ph
Tol
O
O
O
S
S
S
MeOH
reflux
20h
F B
3
Tol
Tol
Tol
Ph
O
O
Ph
O
Ph
5a
O
(E)-form
1
2
3
4
5
6
7
8
9
3a, Ph, Tol
6a
C
B
3b, 4-MeC6H4, Tol
3c, 4-FC6H4, Tol
To explore the substrate scope, the Michael addition of
model substrate 3d (Ar = 4-MeOC6H4, Ar1 = Tol) with
methyl methacrylate was examined next. Because of the
involvement of the methyl group, 4n with two stereocenters
was provided in 72% yields lower than 80% of 4d. The
steric hindrance of the methyl group might affect the
formation of 5n with three stereocenters. The isolated yield
of 5n (65%) was lower than 5d (73%), as shown in Scheme
3, and 6n was separated as a sole isomer in a 60% yield.
3d, 4-MeOC6H4, Tol
3e, 4-CF3C6H4, Tol
3f, 4-NO2C6H4, Tol
3g, 4-PhC6H4, Tol
3h, 2-naphthyl, Tol
3i, 3,4-Cl2C6H4, Tol
4e, 45 5e, ─
4f, ─ 5f, ─
6e, ─
6f, ─
4g, 79 5g, 82 6g, 72
4h, 75 5h, 71 6h, 75
4i, 70 5i, 69 6i, 62
4j, 83 5j, 80 6j, 75
4k, 81 5k, 82 6k, 70
4l, 80 5l, 81 6l, 68
10 3j, Ph, Ph
11 3k, Ph, Me
Scheme 3. Synthesis of 6n
12 3l, Ph, 4-FC6H4
13 3m, Ph, 4-MeOC6H4
CO Me
2
Me
CO Me
2
NaH, THF
reflux, 20 h Me
4m, 82 5m, 82 6m, 65
O
NaBH
BF
3
4
Me
Ar
aThe reaction was run on 3 (1.0 mmol), NaH (120 mg, 5.0
mmol), methyl acrylate (260 mg, 3.0 mmol), THF (10 mL),
reflux, 20 h.
O
S
O
S
O
S
3d
O
Tol
O
Tol
Tol
CO Me
2
MeOH
reflux
20h
MeOH
reflux
20h
Ar
O
Ar
O
O
Me
Ar = 4-MeOC H
bThe reaction was run on 4 (1.0 mmol), NaBH4 (100 mg, 3.0
mmol), MeOH (10 mL), reflux, 20 h.
4n (72%)
5n (65%)
6n (60%)
6
4
cThe reaction was run on 5 (0.5 mmol), boron trifluoride
etherate (142 mg, 1.0 mmol), MeOH (10 mL), reflux, 20 h.
dIsolated yields.
To investigate the introduction of an anisole on skeleton
4, 4a was chosen as the model substrate. Changing the
reaction temperature, NaBH4-mediated reduction of 4a
afforded the intermediate of δ-hydroxy ester at rt for 20
min. Without further purification, boron trifluoride etherate
mediated a stereochemical reaction of the resulting product
with anisole provided 7a at 70% in a two-step reaction, as
shown in Scheme 4. The structural framework of 7a was
determined by single-crystal X-ray crystallography (Figure
1).30 For the formation of 7a, the pathway should show that
boron trifluoride chelated the oxygen atom of the hydroxyl
eThe d.e. of 5 was > 95% by 1H-NMR analysis.
With the experimental results for synthesizing 4a, 5a and
6a in boiling THF or MeOH, the substrate scopes of β-
ketosulfones 3a-m (Ar = Ph, 4-MeC6H4, 4-FC6H4, 4-
MeOC6H4, 4-CF3C6H4, 4-NO2C6H4, 4-PhC6H4, 2-naphthyl,
3,4-Cl2C6H3; Ar1 = Tol, Ph, Me, 4-FC6H4, 4-MeOC6H4)
were investigated, as shown in Table 1. In the Ar

ACCEPTED MANUSCRIPT
Tetrahedron
3
group to lead to D. On the basis of the Felkin─Anh model,
anisole removed BF3-chelated hydroxyl moiety to lead to
7a via an intermolecular stereocontrolled SN2 para-
substitution (back-side attack).
to acid chloride. Without purification, treatment of acid
chloride with AlCl3 gave 8a in a 65% yield. However, no
isolation of the benzannulated skeleton was observed and
only 8a with the (Z)-configuration was formed. This result
was unexpected. We believe that the para-methoxyphenyl
group promoted the intramolecular electrophilic cyclization
of E to form F with a spiro skeleton by the formation of a
blue bond. After performing the dehydrogenative ring-
opening of F, a sulfonyl styrene 8a was formed via the
cleavage of a red bond. From the reaction pathway, we
observed that an intramolecular 1,5-migration of the 4-
methoxyphenyl group (anisole) inhibited the Friedel-Crafts
acylation.
Scheme 4. Synthesis of 7a
MeO
S 2 para-substitution
N
(back-side attack)
CO Me
2
CO Me
2
1) NaBH
MeOH, rt, 20 min
4
H
MeO
CO Me
H
2
O
S
O
S
O
Tol
Tol
O
BF
3
Ph
2) anisole, BF
3
S
Ph
4a
O
CH Cl , rt, 20 h
O
O
O
Ph
2
2
Tol
7a (70%), d.e. > 95%
D
Scheme 6. Synthesis of 9
Figure 1. X-ray structure of 7a
CO Me
2
CO Me
2
CO Me
2
1) NaBH , MeOH, rt, 20 min
4
O
O
S
O
S
O
+
Ph
O
Tol
HO
Tol
Tol
S
2) BF , MeOH, rt, 20 h
3
Ph
4a
O
Ph
O
O
9 (40%)
In adjusting the reaction temperature from reflux to rt
o
(25 C), treatment of 4a with NaBH4 in MeOH at rt for 20
min provided alcohol. Under the rt reduction condition, no
lactone skeleton was detected. Then, using BF3, the
resulting alcohol produced a 40% of γ-sulfonyl ester 9 via a
retro-aldol type reaction (Scheme 6). For the isolated
products, sulfonyl styrene 6a was not observed.
Scheme 7. Synthesis of 10a-b
Scheme 5. Synthesis of 8a
O
S
1
1) NaBH , MeOH, rt, 20 min
4
O
S
1
O
Ar
Ph
Ar
2) BF , MeOH, rt, 20 h
CO Me
2
CO Me
2
3
Ph
O
O
MeO
1) NaBH , MeOH
4
1) 1N NaOH, THF
2) SOCl
1
1
3a, Ar = Tol
10a, Ar = Tol (76%)
O
S
O
S
rt, 20 min
2
O
Tol
Tol
1
1
3k, Ar = Me
10b, Ar = Me (70%)
2) anisole, BF , CH Cl
rt, 20 h
3) AlCl , CH Cl
3
2
2
3
2
2
O
O
However, sulfonyl styrenes 10a-b were generated in
76% and 70% yields, respectively, by the treatment of β-
ketosulfones 3a or 3k (Ar1 = Tol or Me) with similar
conditions (Scheme 7).31-32 For the two-step reaction of
skeletons 3 and 4, we found that the α-substituent was the
only difference, and it caused the generation of two kinds
of distributed products 9 (retro-aldol product) and 10a-b
(dehydrated products).
OMe
4d
OMe
7b (67%)
MeO
1
O
MeO
O
H
O
O
O
5
O
Tol
S
S
S
Tol
Tol
O
O
MeO
O
3. Conclusion
OMe
OMe
OMe
In summary, we developed a facile route for preparing
various γ-sulfonyl lactones 5 and β-sulfonyl styrenes 6 in
moderate to good yields via (1) NaH mediated Michael
addition of β-ketosulfones 3 and methyl acrylate in
refluxing THF, (2) NaBH4 mediated stereoselective
reduction/lactonization of δ-ketoesters 4 in boiling MeOH
or (3) boron trifluoride etherate mediated ring-opening of
lactones 5 in MeOH at reflux. Further investigations
regarding the synthetic application of β-ketosulfones will
be conducted and published.
E
F
8a (65%)
According to the synthetic two-step route of 7a, 7b was
obtained in a 67% yield (Scheme 5). Furthermore, synthesis
of the bicyclic 1-benzosuberone skeleton was examined by
standard transformation (hydrolysis of ester followed by
Friedel-Crafts acylation). First, hydrolysis of ester 7a in the
presence of 1N NaOH solution provided an acid component.
Then, using SOCl2 as the solvent, the acid was transformed

ACCEPTED MANUSCRIPT
4
Tetrahedron
4. Experimental section
5-(4-Fluorophenyl)-5-oxo-4-(toluene-4-sulfonyl)pentanoic
acid methyl ester (4c). Yield = 78% (295 mg); Colorless
o
General. All other reagents and solvents were obtained
from commercial sources and used without further
purification. Reactions were routinely carried out under an
atmosphere of dry air with magnetic stirring. Products in
organic solvents were dried with anhydrous magnesium
sulfate before concentration in vacuo. Melting points were
solid; mp = 120-121 C (recrystallized from hexanes and
EtOAc); IR (CHCl3): 3071, 1754, 1732, 1450, 1043 cm–1;
HRMS (ESI, M++1) calcd for C19H20FO5S 379.1016, found
1
379.1020; H NMR (400 MHz, CDCl3): δ 8.04-7.98 (m,
2H), 7.62 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H),
7.16-7.11 (m, 2H), 5.35-5.32 (m, 1H), 3.59 (s, 3H), 2.47-
2.33 (m, 2H), 2.42 (s, 3H), 2.32-2.22 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ 190.58, 172.49, 166.29 (d, J = 256.2
Hz), 145.57, 133.3 (d, J = 3.0 Hz), 133.00, 131.96 (d, J =
9.8 Hz, 2x), 129.62 (2x), 129.59 (2x), 115.92 (d, J = 22.0
Hz, 2x), 68.42, 51.77, 30.32, 23.25, 21.63.
1
determined with a SMP3 melting apparatus. H and 13C
NMR spectra were recorded on a Varian INOVA-400
spectrometer operating at 400 and at 100 MHz, respectively.
Chemical shifts (δ) are reported in parts per million (ppm)
and the coupling constants (J) are given in Hertz. High
resolution mass spectra (HRMS) were measured with a
mass spectrometer Finnigan/Thermo Quest MAT 95XL. X-
ray crystal structures were obtained with an Enraf-Nonius
FR-590 diffractometer (CAD4, Kappa CCD).
5-(4-Methoxyphenyl)-5-oxo-4-(toluene-4-
sulfonyl)pentanoic acid methyl ester (4d). Yield = 80%
o
(312 mg); Colorless solid; mp = 118-119 C (recrystallized
from hexanes and EtOAc); IR (CHCl3): 3072, 1766, 1742,
1450, 1067 cm–1; HRMS (ESI, M++1) calcd for C20H23O6S
A representative synthetic procedure of skeleton 4 is as
follows: NaH (60% in oil, 120 mg, 5.0 mmol) was added to
a solution of β-ketosulfones 3 (1.0 mmol) in THF (10 mL)
at rt for 5 min. Methyl acrylate (260 mg, 3.0 mmol) in THF
(3 mL) was added to the reaction mixture at rt. Then, the
reaction mixture was stirred at reflux for 20 h. The reaction
mixture was cooled to rt and the solvent was concentrated.
The residue was diluted with water (10 mL) and the
mixture was extracted with CH2Cl2 (3 x 20 mL). The
combined organic layers were washed with brine, dried,
filtered and evaporated to afford crude product. Purification
on silica gel (hexanes/EtOAc = 8/1~1/1) afforded skeleton
4.
1
391.1215, found 391.1223; H NMR (400 MHz, CDCl3): δ
7.94 (d, J = 8.8 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.27 (d, J
= 8.0 Hz, 2H), 6.91 (d, J = 9.2 Hz, 2H), 5.29 (dd, J = 4.0,
9.6 Hz, 1H), 3.85 (s, 3H), 3.57 (s, 3H), 2.42-2.34 (m, 2H),
2.39 (s, 3H), 2.32-2.20 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ 190.02, 172.43, 164.32, 145.24, 133.15, 131.56
(2x), 129.84, 129.55 (2x), 129.43 (2x), 131.86 (2x), 68.00,
55.49, 51.64, 30.34, 23.22, 21.55.
5-Oxo-4-(toluene-4-sulfonyl)-5-(4-
trifluoromethylphenyl)pentanoic acid methyl ester (4e).
o
Yield = 45% (193 mg); Colorless solid; mp = 100-111 C
(recrystallized from hexanes and EtOAc); IR (CHCl3):
3052, 1753, 1732, 1454, 1062 cm–1; HRMS (ESI, M++1)
calcd for C20H20F3O5S 429.0984, found 429.0986; 1H NMR
(400 MHz, CDCl3): δ 8.06 (d, J = 8.4 Hz, 2H), 7.72 (d, J =
8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz,
2H), 5.42-5.38 (m, 1H), 3.60 (s, 3H), 2.53-2.23 (m, 4H),
2.41 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.63,
172.54, 145.78, 139.49, 135.20, 133.06, 129.69 (2x),
129.62 (4x), 129.43 (2x), 125.73 (q, J = 3.8 Hz), 68.91,
51.82, 30.34, 23.08, 21.60.
5-Oxo-5-phenyl-4-(toluene-4-sulfonyl)pentanoic
acid
methyl ester (4a). Yield = 85% (306 mg); Colorless solid;
mp = 130-131 oC (recrystallized from hexanes and EtOAc);
IR (CHCl3): 3068, 1760, 1738, 1453, 1058 cm–1; HRMS
(ESI, M++1) calcd for C19H21O5S 361.1110, found
1
361.1115; H NMR (400 MHz, CDCl3): δ 7.97-7.94 (m,
2H), 7.63 (d, J = 8.4 Hz, 2H), 7.62-7.58 (m, 1H), 7.49-7.45
(m, 2H), 7.29 (d, J = 8.4 Hz, 2H), 5.36 (dd, J = 4.4, 9.6 Hz,
1H), 3.59 (s, 3H), 2.48-2.35 (m, 2H), 2.42 (s, 3H), 2.41-
2.21 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 192.23,
172.47, 145.45, 136.90, 134.07, 133.26, 129.70 (2x),
129.58 (2x), 129.12 (2x), 128.74 (2x), 68.47, 51.76, 30.46,
23.35, 21.65.
5-Biphenyl-4-yl-5-oxo-4-(toluene-4-sulfonyl)pentanoic acid
methyl ester (4g). Yield = 79% (344 mg); Colorless solid;
o
mp = 75-76 C (recrystallized from hexanes and EtOAc);
IR (CHCl3): 3070, 1752, 1730, 1445, 1052 cm–1; HRMS
(ESI, M++1) calcd for C25H25O5S 437.1423, found
5-Oxo-4-(toluene-4-sulfonyl)-5-p-tolylpentanoic
acid
1
methyl ester (4b). Yield = 86% (322 mg); Colorless solid;
mp = 118-119 oC (recrystallized from hexanes and EtOAc);
IR (CHCl3): 3062, 1759, 1737, 1456, 1060 cm–1; HRMS
(ESI, M++1) calcd for C20H23O5S 375.1266, found
437.1430; H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.8
Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H),
7.62-7.59 (m, 2H), 7.49-7.45 (m, 2H), 7.43-7.39 (m, 1H),
7.29 (d, J = 8.4 Hz, 2H), 5.42 (dd, J = 4.4, 9.2 Hz, 1H),
3.59 (s, 3H), 2.48-2.41 (m, 2H), 2.39 (s, 3H), 2.37-2.26 (m,
2H); 13C NMR (100 MHz, CDCl3): δ 191.54, 172.41,
146.63, 145.36, 139.35, 135.48, 133.21, 129.67 (2x),
129.59 (2x), 129.50 (2x), 128.90 (2x), 128.40, 127.22 (2x),
127.16 (2x), 68.40, 54.65, 30.38, 23.22, 21.54.
1
375.1268; H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.0
Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H),
7.23 (d, J = 8.0 Hz, 2H), 5.33-5.30 (m, 1H), 3.56 (s, 3H),
2.43-2.33 (m, 2H), 2.38 (br s, 6H), 2.31-2.21 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ 191.47, 172.34, 145.25, 145.16,
134.37, 133.25, 129.52 (2x), 129.43 (2x), 129.32 (2x),
129.15 (2x), 68.21, 51.59, 30.35, 23.21, 21.56, 21.50.
5-Naphthalen-2-yl-5-oxo-4-(toluene-4-sulfonyl)pentanoic
acid methyl ester (4h). Yield = 75% (308 mg); Colorless
o
solid; mp = 107-108 C (recrystallized from hexanes and

ACCEPTED MANUSCRIPT
Tetrahedron
5
EtOAc); IR (CHCl3): 3072, 1764, 1741, 1455, 1054 cm–1;
HRMS (ESI, M++1) calcd for C23H23O5S 411.1266, found
411.1268; H NMR (400 MHz, CDCl3): δ 8.46 (s, 1H),
7.99-7.96 (m, 2H), 7.88-7.85 (m, 2H), 7.65 (d, J = 8.0 Hz,
2H), 7.63-7.54 (m, 2H), 7.24 (d, J = 8.0 Hz, 2H), 5.54-5.51
(m, 1H), 3.58 (s, 3H), 2.51-2.28 (m, 4H), 2.33 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 191.99, 172.51, 145.43, 135.85,
134.22, 133.31, 132.25, 131.68, 129.96, 129.65 (2x),
129.54 (2x), 129.18, 128.63, 127.68, 126.97, 123.95, 68.64,
51.73, 30.50, 23.29, 21.52.
J = 3.0 Hz), 129.06 (2x), 128.84 (2x), 116.28 (d, J = 22.7
Hz, 2x), 68.40, 51.80, 30.34, 23.37.
1
4-(4-Methoxybenzenesulfonyl)-5-oxo-5-phenylpentanoic
acid methyl ester (4m). Yield = 82% (308 mg); Colorless
o
solid; mp = 129-130 C (recrystallized from hexanes and
EtOAc); IR (CHCl3): 3069, 1765, 1733, 1451, 1048 cm–1;
HRMS (ESI, M++1) calcd for C19H21O6S 377.1059, found
1
377.1063; H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 8.4
Hz, 2H), 7.59 (d, J = 8.8 Hz, 2H), 7.49-7.45 (m, 1H), 7.36-
7.32 (m, 2H), 6.83 (d, J = 8.8 Hz, 2H), 5.34-5.30 (m, 1H),
3.70 (s, 3H), 3.46 (s, 3H), 2.38-2.16 (m, 4H); 13C NMR
(100 MHz, CDCl3): δ 192.01, 172.06, 163.84, 136.57,
133.66, 131.36 (2x), 128.64 (2x), 128.35 (2x), 127.50,
113.84 (2x), 68.09, 55.31, 51.28, 30.09, 22.94.
5-(3,4-Dichlorophenyl)-5-oxo-4-(toluene-4-
sulfonyl)pentanoic acid methyl ester (4i). Yield = 70% (300
mg); Colorless solid; mp = 127-128 oC (recrystallized from
hexanes and EtOAc); IR (CHCl3): 3072, 1762, 1741, 1421,
1055 cm–1; HRMS (ESI, M++1) calcd for C19H19Cl2O5S
A representative synthetic procedure of skeleton 5 is as
follows: NaBH4 (100 mg, 3.0 mmol) was added to a
solution of esters 4 (1.0 mmol) in MeOH (10 mL) at rt for 5
min. Then, the reaction mixture was stirred at reflux for 20
h. The reaction mixture was cooled to rt and the solvent
was concentrated. The residue was diluted with water (10
mL) and the mixture was extracted with CH2Cl2 (3 x 20
mL). The combined organic layers were washed with brine,
dried, filtered and evaporated to afford crude product.
Purification on silica gel (hexanes/EtOAc = 8/1~1/1)
afforded skeleton 5.
1
429.0330, found 429.0338; H NMR (400 MHz, CDCl3): δ
7.93 (d, J = 2.0 Hz, 1H), 7.78 (dd, J = 2.4, 8.4 Hz, 1H),
7.56 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.4 Hz, 1H), 7.25 (d, J
= 8.4 Hz, 2H), 5.28 (dd, J = 4.4, 9.2 Hz, 1H), 3.55 (s, 3H),
2.54-2.20 (m, 4H), 2.37 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 190.12, 172.31, 145.66, 138.49, 136.23, 133.19,
132.82, 130.61 (2x), 129.53 (2x), 129.37 (2x), 128.07,
68.53, 51.63, 30.18, 22.83, 21.44.
4-Benzenesulfonyl-5-oxo-5-phenylpentanoic acid methyl
ester (4j). Yield = 83% (287 mg); Colorless solid; mp =
o
113-114 C (recrystallized from hexanes and EtOAc); IR
6-Phenyl-5-(toluene-4-sulfonyl)tetrahydropyran-2-one (5a).
(CHCl3): 3072, 1764, 1731, 1450, 1045 cm–1; HRMS (ESI,
o
Yield = 86% (284 mg); Colorless solid; mp = 159-160 C
1
M++1) calcd for C18H19O5S 347.0953, found 347.0956; H
(recrystallized from hexanes and EtOAc); d.e. > 95%; IR
NMR (400 MHz, CDCl3): δ 7.95-7.92 (m, 2H), 7.78-7.75
(m, 2H), 7.64-7.56 (m, 2H), 7.51-7.43 (m, 4H), 5.40 (dd, J
= 4.4, 9.6 Hz, 1H), 3.58 (s, 3H), 2.49-2.22 (m, 4H); 13C
NMR (100 MHz, CDCl3): δ 192.06, 172.42, 136.80, 136.36,
134.24, 134.11, 129.59 (2x), 129.01 (2x), 128.90 (2x),
128.74 (2x), 68.35, 51.73, 30.39, 23.22.
(CHCl3): 3073, 1742, 1438, 1028 cm–1; HRMS (ESI, M++1)
1
calcd for C18H19O4S 331.1004, found 331.1012; H NMR
(400 MHz, CDCl3): δ 7.63 (d, J = 8.4 Hz, 2H), 7.30-7.23
(m, 5H), 7.15-7.11 (m, 2H), 5.79 (d, J = 5.6 Hz, 1H), 3.70-
3.65 (m, 1H), 2.96-2.88 (m, 1H), 2.62-2.45 (m, 2H), 2.41 (s,
3H), 2.29-2.19 (m, 1H); 13C NMR (100 MHz, CDCl3): δ
169.61, 145.41, 137.17, 134.13, 130.01 (2x), 128.84,
128.80 (2x), 128.60 (2x), 126.33 (2x), 77.99, 62.27, 27.14,
21.60, 18.37.
4-Methanesulfonyl-5-oxo-5-phenylpentanoic acid methyl
ester (4k). Yield = 81% (230 mg); Colorless gum; IR
(CHCl3): 3053, 1761, 1734, 1457, 1041 cm–1; HRMS (ESI,
1
M++1) calcd for C13H17O5S 285.0797, found 285.0802; H
5-(Toluene-4-sulfonyl)-6-p-tolyltetrahydropyran-2-one (5b).
NMR (400 MHz, CDCl3): δ 8.02-8.00 (m, 2H), 7.63-7.58
(m, 1H), 7.50-7.46 (m, 2H), 5.13 (t, J = 6.4 Hz, 1H), 3.57 (s,
3H), 2.92 (s, 3H), 2.51-2.43 (m, 3H), 2.39-2.32 (m, 1H);
13C NMR (100 MHz, CDCl3): δ 193.34, 172.08, 136.23,
134.44, 129.09 (2x), 128.82 (2x), 67.26, 51.68, 37.44,
30.49, 23.86.
o
Yield = 82% (282 mg); Colorless solid; mp = 126-127 C
(recrystallized from hexanes and EtOAc); d.e. > 95%; IR
(CHCl3): 3078, 1745, 1423, 1026 cm–1; HRMS (ESI, M++1)
1
calcd for C19H21O4S 345.1161, found 345.1163; H NMR
(400 MHz, CDCl3): δ 7.60 (d, J = 8.0 Hz, 2H), 7.23 (d, J =
8.0 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.4 Hz,
2H), 5.72 (d, J = 6.0 Hz, 1H), 3.67 (dd, J = 5.6, 12.8 Hz,
1H), 2.93-2.85 (m, 1H), 2.61-2.43 (m, 2H), 2.41 (s, 3H),
2.29 (s, 3H), 2.28-2.20 (m, 1H); 13C NMR (100 MHz,
CDCl3): δ 169.72, 145.23, 138.86, 134.24, 134.01, 129.87
(2x), 129.36 (2x), 128.55 (2x), 126.34 (2x), 77.99, 62.25,
27.18, 21.56, 21.03, 18.37.
4-(4-Fluorobenzenesulfonyl)-5-oxo-5-phenylpentanoic acid
methyl ester (4l). Yield = 80% (291 mg); Colorless solid;
mp = 119-120 oC (recrystallized from hexanes and EtOAc);
IR (CHCl3): 3067, 1761, 1734, 1450, 1049 cm–1; HRMS
(ESI, M++1) calcd for C18H18FO5S 365.0859, found
1
365.0853; H NMR (400 MHz, CDCl3): δ 7.96-7.93 (m,
2H), 7.80-7.75 (m, 2H), 7.63-7.59 (m, 1H), 7.49-7.45 (m,
2H), 7.20-7.14 (m, 2H), 5.40 (dd, J = 4.4, 9.2 Hz, 1H), 3.60
(s, 3H), 2.51-2.37 (m, 2H), 2.34-2.22 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ 192.17, 172.40, 166.19 (d, J = 256.2
Hz), 136.69, 134.30, 132.62 (d, J = 9.9 Hz, 2x), 132.15 (d,
6-(4-Fluorophenyl)-5-(toluene-4-sulfonyl)tetrahydropyran-
2-one (5c). Yield = 78% (271 mg); Colorless solid; mp =
o
179-180 C (recrystallized from hexanes and EtOAc); d.e.
> 95%; IR (CHCl3): 3082, 1740, 1443, 1033 cm–1; HRMS
(ESI, M++1) calcd for C18H18FO4S 349.0910, found
1
349.0912; H NMR (400 MHz, CDCl3): δ 7.54 (d, J = 8.4

ACCEPTED MANUSCRIPT
6
Tetrahedron
Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.14-7.09 (m, 2H), 6.92-
6.87 (m, 2H), 5.68 (d, J = 7.2 Hz, 1H), 3.70-3.65 (m, 1H),
2.94-2.86 (m, 1H), 2.64-2.46 (m, 2H), 2.39 (s, 3H), 2.31-
2.21 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 169.63,
162.84 (d, J = 247.9 Hz), 145.41, 134.24, 132.65 (d, J = 3.0
Hz), 129.90 (2x), 128.83 (d, J = 8.4 Hz, 2x), 128.41 (2x),
115.64 (d, J = 22.0 Hz, 2x), 77.76, 62.26, 27.33, 21.52,
18.84.
= 8.4 Hz, 1H), 7.12 (d, J = 2.4 Hz, 1H), 7.04 (dd, J = 2.0,
8.4 Hz, 1H), 5.57 (d, J = 8.0 Hz, 1H), 3.67-3.62 (m, 2H),
2.98-2.90 (m, 1H), 2.70-2.55 (m, 2H), 2.43 (s, 3H), 2.39-
2.29 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 169.20,
145.82, 137.62, 136.45, 134.23, 133.00, 130.67, 129.95
(2x), 129.31, 128.29 (2x), 126.64, 77.49, 62.25, 27.55,
21.65, 19.00.
5-Benzenesulfonyl-6-phenyltetrahydropyran-2-one
(5j).
o
6-(4-Methoxyphenyl)-5-(toluene-4-
Yield = 80% (253 mg); Colorless solid; mp = 138-139 C
(recrystallized from hexanes and EtOAc); d.e. > 95%; IR
(CHCl3): 3069, 1744, 1432, 1021 cm–1; HRMS (ESI, M++1)
sulfonyl)tetrahydropyran-2-one (5d). Yield = 73% (263
mg); Colorless solid; mp = 155-156 oC (recrystallized from
hexanes and EtOAc); d.e. > 95%; IR (CHCl3): 3073, 1744,
1431, 1028 cm–1; HRMS (ESI, M++1) calcd for C19H21O5S
1
calcd for C17H17O4S 317.0848, found 317.0853; H NMR
(400 MHz, CDCl3): δ 7.73-7.71 (m, 2H), 7.60-7.56 (m, 2H),
7.46-7.42 (m, 2H), 7.25-7.20 (m, 2H), 7.13-7.10 (m, 2H),
5.78 (d, J = 6.4 Hz, 1H), 3.72 (q, J = 6.0 Hz, 1H), 2.97-2.88
(m, 1H), 2.64-2.57 (m, 1H), 2.54-2.46 (m, 1H), 2.31-2.22
(m, 1H); 13C NMR (100 MHz, CDCl3): δ 169.51, 137.23,
136.85, 134.10, 129.32 (2x), 128.98, 128.78 (2x), 128.46
(2x), 126.42 (2x), 78.02, 62.13, 27.15, 18.31.
1
361.1110, found 361.1113; H NMR (400 MHz, CDCl3): δ
7.54 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.03 (d, J
= 8.8 Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H), 5.65 (d, J = 6.8 Hz,
1H), 3.75 (s, 3H), 3.68 (q, J = 7.2 Hz, 1H), 2.93-2.85 (m,
1H), 2.63-2.47 (m, 2H), 2.39 (s, 3H), 2.32-2.23 (m, 1H);
13C NMR (100 MHz, CDCl3): δ 169.88, 160.02, 145.08,
134.41, 129.82 (2x), 128.68, 128.46 (2x), 128.12 (2x),
114.02 (2x), 78.10, 62.26, 55.24, 27.36, 21.53, 18.65.
5-Methanesulfonyl-6-phenyltetrahydropyran-2-one
(5k).
o
Yield = 82% (208 mg); Colorless solid; mp = 159-160 C
(recrystallized from hexanes and EtOAc); d.e. > 95%; IR
(CHCl3): 3070, 1745, 1440, 1024 cm–1; HRMS (ESI, M++1)
6-Biphenyl-4-yl-5-(toluene-4-sulfonyl)tetrahydropyran-2-
one (5g). Yield = 82% (333 mg); Colorless gum; d.e. >
95%; IR (CHCl3): 3072, 1742, 1440, 1025 cm–1; HRMS
(ESI, M++1) calcd for C24H23O4S 407.1317, found
1
calcd for C12H15O4S 255.0691, found 255.0698; H NMR
(400 MHz, CDCl3): δ 7.46-7.42 (m, 5H), 5.59 (d, J = 8.8
Hz, 1H), 3.59-3.53 (m, 1H), 2.92-2.84 (m, 1H), 2.71-2.64
(m, 1H), 2.61-2.52 (m, 1H), 2.44-2.35 (m, 1H), 2.27 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 169.86, 136.23, 130.02,
129.28 (2x), 127.66 (2x), 79.13, 62.13, 41.07, 27.75, 18.16.
1
407.1319; H NMR (400 MHz, CDCl3): δ 7.59 (d, J = 8.4
Hz, 2H), 7.51 (d, J = 8.8 Hz, 2H), 7.46-7.42 (m, 4H), 7.39-
7.35 (m, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz,
2H), 5.78 (d, J = 6.4 Hz, 1H), 3.75 (q, J = 6.4 Hz, 1H),
2.99-2.90 (m, 1H), 2.68-2.51 (m, 1H), 2.48-2.42 (m, 1H),
2.38-2.21 (m, 1H), 2.34 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 169.68, 145.24, 141.93, 139.98, 135.60, 134.31,
129.88 (2x), 128.83 (2x), 128.49 (2x), 127.72, 127.36 (2x),
127.11 (2x), 126.97 (2x), 78.10, 62.23, 27.33, 21.55, 18.50.
5-(4-Fluorobenzenesulfonyl)-6-phenyltetrahydropyran-2-
one (5l). Yield = 81% (271 mg); Colorless solid; mp = 96-
97 oC (recrystallized from hexanes and EtOAc); d.e. > 95%;
IR (CHCl3): 3080, 1735, 1440, 1031 cm–1; HRMS (ESI,
M++1) calcd for C17H16FO4S 335.0753, found 335.0759; 1H
NMR (400 MHz, CDCl3): δ 7.68-7.63 (m, 2H), 7.27-7.18
(m, 3H), 7.12-7.09 (m, 2H), 7.07-7.01 (m, 2H), 5.69 (d, J =
6.8 Hz, 1H), 3.75 (q, J = 6.8 Hz, 1H), 2.94-2.85 (m, 1H),
2.65-2.57 (m, 1H), 2.54-2.46 (m, 1H), 2.35-2.25 (m, 1H);
13C NMR (100 MHz, CDCl3): δ 168.26 (d, J = 251.7 Hz),
164.45, 136.32, 133.32 (d, J = 3.1 Hz), 131.26 (d, J = 9.9
Hz, 2x), 129.08, 128.73 (2x), 126.72 (2x), 116.51 (d, J =
22.0 Hz, 2x), 78.26, 62.08, 27.23, 18.37.
6-Naphthalen-2-yl-5-(toluene-4-sulfonyl)tetrahydropyran-
2-one (5h). Yield = 71% (270 mg); Colorless solid; mp =
o
188-189 C (recrystallized from hexanes and EtOAc); d.e.
> 95%; IR (CHCl3): 3072, 1761, 1738, 1453, 1028 cm–1;
HRMS (ESI, M++1) calcd for C22H21O4S 381.1161, found
1
381.1168; H NMR (400 MHz, CDCl3): δ 7.77-7.75 (m,
1H), 7.72-7.69 (m, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.54 (br s,
1H), 7.51 (d, J = 8.4 Hz, 2H), 7.52-7.47 (m, 2H), 7.16 (dd,
J = 2.0, 8.4 Hz, 1H), 6.99 (d, J = 8.0 Hz, 2H), 5.86 (d, J =
6.8 Hz, 1H), 3.81 (dd, J = 6.8, 12.8 Hz, 1H), 3.01-2.93 (m,
1H), 2.70-2.54 (m, 2H), 2.39-2.30 (m, 1H), 2.18 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 169.78, 145.21, 134.17,
133.75, 133.20, 132.69, 129.65 (2x), 128.87, 128.32 (2x),
128.05, 127.51, 126.84, 126.69, 126.64, 123.33, 78.55,
62.06, 27.43, 21.35, 18.47.
5-(4-Methoxybenzenesulfonyl)-6-phenyltetrahydropyran-2-
one (5m). Yield = 82% (284 mg); Colorless gum; d.e. >
95%; IR (CHCl3): 3076, 1738, 1435, 1028 cm–1; HRMS
(ESI, M++1) calcd for C18H19O5S 347.0953, found
1
347.0959; H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 8.8
Hz, 2H), 7.27-7.24 (m, 3H), 7.14-7.11 (m, 2H), 6.88 (d, J =
9.2 Hz, 2H), 6.76 (d, J = 5.6 Hz, 1H), 3.83 (s, 3H), 3.67 (q,
J = 6.0 Hz, 1H), 2.93-2.85 (m, 1H), 2.60-2.53 (m, 1H),
2.50-2.42 (m, 1H), 2.28-2.20 (m, 1H); 13C NMR (100 MHz,
CDCl3): δ 169.64, 164.02, 137.14, 130.71 (2x), 128.81,
128.74 (2x), 126.30 (2x), 125.20, 114.55 (2x), 78.08, 62.22,
55.67, 27.08, 18.34.
6-(3,4-Dichlorophenyl)-5-(toluene-4-
sulfonyl)tetrahydropyran-2-one (5i). Yield = 69% (275 mg);
o
Colorless solid; mp > 250 C (recrystallized from hexanes
and EtOAc); d.e. > 95%; IR (CHCl3): 3068, 1735, 1428,
1022 cm–1; HRMS (ESI, M++1) calcd for C18H17Cl2O4S
1
399.0225, found 399.0229; H NMR (400 MHz, CDCl3): δ
A representative synthetic procedure of skeleton 6 is as
follows: Boron trifluoride etherate (142 mg, 1.0 mmol) was
7.51 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.4 Hz, 1H), 7.30 (d, J

ACCEPTED MANUSCRIPT
Tetrahedron
7
1
added to a solution of lactones 5 (0.5 mmol) in MeOH (10
mL) at rt for 5 min. Then, the reaction mixture was stirred
at reflux for 20 h. The reaction mixture was cooled to rt and
the solvent was concentrated. The residue was diluted with
water (10 mL) and the mixture was extracted with CH2Cl2
(3 x 20 mL). The combined organic layers were washed
with brine, dried, filtered and evaporated to afford crude
product. Purification on silica gel (hexanes/EtOAc =
8/1~1/1) afforded skeleton 6.
M++1) calcd for C25H25O4S 421.1474, found 421.1479; H
NMR (400 MHz, CDCl3): δ 7.88 (s, 1H), 7.82 (d, J = 8.4
Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.62-7.59 (m, 2H), 7.51
(d, J = 8.0 Hz, 2H), 7.48-7.44 (m, 2H), 7.40-7.37 (m, 1H),
7.35 (d, J = 8.4 Hz, 2H), 3.67 (s, 3H), 2.87-2.82 (m, 2H),
2.67-2.63 (m, 2H), 2.45 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 172.58, 144.44, 142.57, 139.86, 139.71, 138.39,
136.26, 132.06, 129.99 (2x), 129.97 (2x), 128.93 (2x),
128.24 (2x), 127.97, 127.61 (2x), 127.05 (2x), 51.82, 32.55,
22.59, 21.61.
5-Phenyl-4-(toluene-4-sulfonyl)pent-4-enoic acid methyl
ester (6a). Yield = 76% (131 mg); Colorless gum; IR
(CHCl3): 3062, 1730, 1450, 1103 cm–1; HRMS (ESI, M++1)
5-Naphthalen-2-yl-4-(toluene-4-sulfonyl)pent-4-enoic acid
methyl ester (6h). Yield = 75% (148 mg); Colorless gum;
IR (CHCl3): 3050, 1736, 1460, 1098 cm–1; HRMS (ESI,
1
calcd for C19H21O4S 345.1161, found 345.1168; H NMR
1
(400 MHz, CDCl3): δ 7.85 (s, 1H), 7.80 (d, J = 8.4 Hz, 2H),
7.45-7.36 (m, 5H), 7.34 (d, J = 8.8 Hz, 2H), 3.65 (s, 3H),
2.81-2.77 (m, 2H), 2.63-2.59 (m, 2H), 2.44 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 172.53, 144.44, 139.98, 138.89,
136.19, 133.21, 129.95 (2x), 129.73, 129.30 (2x), 129.00
(2x), 128.21 (2x), 51.77, 32.54, 22.42, 21.59.
M++1) calcd for C23H23O4S 395.1317, found 395.1312; H
NMR (400 MHz, CDCl3): δ 8.00 (s, 1H), 7.93 (s, 1H),
7.89-7.82 (m, 6H), 7.56-7.49 (m, 2H), 7.36 (d, J = 8.0 Hz,
2H), 3.65 (s, 3H), 2.91-2.87 (m, 2H), 2.67-2.63 (m, 2H),
2.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 172.57,
144.46, 140.10, 138.89, 136.27, 133.50, 133.13, 130.65,
129.99 (2x), 129.93, 128.77, 128.56, 128.27 (2x), 127.68,
127.45, 126.84, 125.83, 51.80, 32.71, 22.60, 21.61.
4-(Toluene-4-sulfonyl)-5-p-tolylpent-4-enoic acid methyl
ester (6b). Yield = 75% (134 mg); Colorless gum; IR
(CHCl3): 3063, 1728, 1453, 1110 cm–1; HRMS (ESI, M++1)
5-(3,4-Dichlorophenyl)-4-(toluene-4-sulfonyl)pent-4-enoic
acid methyl ester (6i). Yield = 62% (128 mg); Colorless
gum; IR (CHCl3): 3054, 1740, 1454, 1114 cm–1; HRMS
(ESI, M++1) calcd for C19H19Cl2O4S 413.0381, found
1
calcd for C20H23O4S 359.1317, found 359.1323; H NMR
(400 MHz, CDCl3): δ 7.80 (s, 1H), 7.79 (d, J = 8.4 Hz, 2H),
7.34-7.31 (m, 4H), 7.22 (d, J = 8.0 Hz, 2H), 3.65 (s, 3H),
2.81-2.77 (m, 2H), 2.62-2.58 (m, 2H), 2.43 (s, 3H), 2.37 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 172.63, 144.31,
140.24, 138.85, 138.71, 136.36, 130.33, 129.91 (2x),
129.75 (2x), 129.46 (2x), 128.18 (2x), 51.77, 32.47, 22.49,
21.58, 21.36.
1
413.0385; H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.0
Hz, 2H), 7.72 (s, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.36 (d, J =
8.0 Hz, 2H), 7.24 (dd, J = 2.0, 8.4 Hz, 1H), 3.65 (s, 3H),
2.77-2.73 (m, 2H), 2.59-2.55 (m, 2H), 2.45 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 172.21, 144.82, 142.34, 136.18,
135.73, 133.93, 133.38, 133.18, 131.05, 131.00, 130.09
(2x), 128.33 (2x), 128.13, 51.89, 32.47, 29.68, 22.36.
5-(4-Fluorophenyl)-4-(toluene-4-sulfonyl)pent-4-enoic acid
methyl ester (6c). Yield = 70% (127 mg); Colorless gum;
IR (CHCl3): 3058, 1731, 1452, 1110 cm–1; HRMS (ESI,
M++1) calcd for C19H20FO4S 363.1066, found 363.1072; 1H
NMR (400 MHz, CDCl3): δ 7.80 (s, 1H), 7.79 (d, J = 8.0
Hz, 2H), 7.43-7.40 (m, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.14-
7.09 (m, 2H), 3.65 (s, 3H), 2.79-2.75 (m, 2H), 2.60-2.56 (m,
2H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 172.46,
163.28 (d, J = 250.9 Hz), 144.53, 139.78, 137.61, 136.09,
131.39 (d, J = 7.5 Hz, 2x), 129.99 (2x), 129.35 (d, J = 3.8
Hz), 128.88 (2x), 116.22 (d, J = 22.0 Hz, 2x), 51.82, 32.41,
22.35, 21.60.
4-Benzenesulfonyl-5-phenylpent-4-enoic acid methyl ester
(6j). Yield = 75% (124 mg); Colorless gum; IR (CHCl3):
3068, 1731, 1451, 1107 cm–1; HRMS (ESI, M++1) calcd for
C18H19O4S 331.1004, found 331.1109; 1H NMR (400 MHz,
CDCl3): δ 7.94-7.92 (m, 2H), 7.87 (s, 1H), 7.65-7.61 (m,
1H), 7.57-7.53 (m, 2H), 7.43-7.38 (m, 5H), 3.64 (s, 3H),
2.82-2.78 (m, 2H), 2.63-2.58 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ 172.46, 139.66, 139.38, 139.20, 133.42, 133.09,
129.84, 129.33 (2x), 129.31 (2x), 129.02 (2x), 128.14 (2x),
51.77, 32.48, 22.44.
5-(4-Methoxyphenyl)-4-(toluene-4-sulfonyl)pent-4-enoic
acid methyl ester (6d). Yield = 68% (127 mg); Colorless
gum; IR (CHCl3): 3057, 1728, 1452, 1097 cm–1; HRMS
(ESI, M++1) calcd for C20H23O5S 375.1266, found
4-Methanesulfonyl-5-phenylpent-4-enoic acid methyl ester
(6k). Yield = 70% (94 mg); Colorless gum; IR (CHCl3):
3069, 1733, 1452, 1114 cm–1; HRMS (ESI, M++1) calcd for
C13H17O4S 269.0848, found 269.0853; 1H NMR (400 MHz,
CDCl3): δ 7.69 (s, 1H), 7.46-7.39 (m, 5H), 3.69 (s, 3H),
3.04-3.00 (m, 2H), 3.01 (s, 3H), 2.77-2.73 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ 172.50, 140.05, 139.66, 132.94,
129.90 (2x), 129.23 (2x), 129.07, 51.87, 41.30, 32.61,
22.79.
1
375.1269; H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.4
Hz, 2H), 7.77 (s, 1H), 7.41 (d, J = 8.8 Hz, 2H), 7.33 (d, J =
7.6 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H), 3.66 (s,
3H), 2.82-2.78 (m, 2H), 2.62-2.58 (m, 2H), 2.43 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 172.71, 160.89, 144.22,
138.37, 136.92, 136.52, 131.44 (2x), 129.90 (2x), 128.12
(2x), 125.64, 114.52 (2x), 55.38, 51.80, 32.38, 22.54, 21.58.
4-(4-Fluorobenzenesulfonyl)-5-phenylpent-4-enoic
acid
methyl ester (6l). Yield = 68% (118 mg); Colorless gum; IR
5-Biphenyl-4-yl-4-(toluene-4-sulfonyl)pent-4-enoic
acid
(CHCl3): 3060, 1741, 1452, 1093 cm–1; HRMS (ESI, M++1)
1
methyl ester (6g). Yield = 72% (151 mg); Colorless gum;
calcd for C18H18FO4S 349.0910, found 349.0915; H NMR
IR (CHCl3): 3056, 1732, 1445, 1096 cm–1; HRMS (ESI,
(400 MHz, CDCl3): δ 7.96-7.93 (m, 2H), 7.86 (s, 1H), 7.46-

ACCEPTED MANUSCRIPT
8
Tetrahedron
7.40 (m, 5H), 7.25-7.20 (m, 2H), 3.66 (s, 3H), 2.81-2.77 (m,
2H), 2.64-2.60 (m, 2H); 13C NMR (100 MHz, CDCl3): δ
172.42, 165.68 (d, J = 254.7 Hz), 139.59, 135.26 (d, J = 3.1
Hz), 132.97, 131.01 (d, J = 9.1 Hz, 2x), 129.96, 129.35 (2x),
129.08 (2x), 116.66 (d, J = 22.0 Hz, 2x), 70.56, 51.83,
32.50, 22.44.
131.28 (2x), 129.76 (2x), 128.08 (2x), 125.70, 114.23 (2x),
55.27, 51.69, 37.45, 29.81, 21.49, 16.43.
A representative synthetic procedure of compounds 7a-b is
as follows: NaBH4 (100 mg, 3.0 mmol) was added to a
solution of lactones 5a (165 mg, 0.5 mmol) or 5d (180 mg,
0.5 mmol) in MeOH (10 mL) at rt for 20 min. The reaction
mixture was concentrated. The residue was diluted with
water (10 mL) and the mixture was extracted with CH2Cl2
(3 x 20 mL). The combined organic layers were washed
with brine, dried, filtered and evaporated to afford crude
product. Without further purification, boron trifluoride
etherate (284 mg, 2.0 mmol) was added to a solution of the
resulting products and anisole (216 mg, 2.0 mmol) in
CH2Cl2 (10 mL) at rt for 20 h. The reaction mixture was
concentrated. The residue was diluted with water (10 mL)
and the mixture was extracted with CH2Cl2 (3 x 20 mL).
The combined organic layers were washed with brine, dried,
filtered and evaporated to afford crude products.
Purification on silica gel (hexanes/EtOAc = 8/1~1/1)
afforded compounds 7a-b.
4-(4-Methoxybenzenesulfonyl)-5-phenylpent-4-enoic acid
methyl ester (6m). Yield = 65% (117 mg); Colorless gum;
IR (CHCl3): 3068, 1733, 1454, 1114 cm–1; HRMS (ESI,
1
M++1) calcd for C19H21O5S 361.1110, found 361.1115; H
NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.4 Hz, 2H), 7.82
(s, 1H), 7.42-7.37 (m, 5H), 7.00 (d, J = 8.8 Hz, 2H), 3.87 (s,
3H), 3.64 (s, 3H), 2.81-2.77 (m, 2H), 2.62-2.58 (m, 2H);
13C NMR (100 MHz, CDCl3): δ 172.51, 163.58, 140.25,
138.39, 133.23, 130.50, 130.35 (2x), 129.63, 129.23 (2x),
128.96 (2x), 114.54 (2x), 55.63, 51.73, 32.55, 22.35.
2-Methyl-5-(4-methoxyphenyl)-4-(toluene-4-sulfonyl)pent-
4-enoic acid methyl ester (6n). NaH (60% in oil, 120 mg,
5.0 mmol) was added to a solution of 3d (304 mg, 1.0
mmol) in THF (10 mL) at rt for 5 min. Methyl methacrylate
(300 mg, 3.0 mmol) in THF (3 mL) was added to the
reaction mixture at rt. Then, the reaction mixture was
stirred at reflux for 20 h. The reaction mixture was cooled
to rt and the solvent was concentrated. The residue was
diluted with water (10 mL) and the mixture was extracted
with CH2Cl2 (3 x 20 mL). The combined organic layers
were washed with brine, dried, filtered and evaporated to
afford crude product. Purification on silica gel
(hexanes/EtOAc = 8/1~1/1) afforded 4n. Yield = 72% (291
mg). Then, NaBH4 (75 mg, 2.16 mmol) was added to a
solution of the resulting product 4n (291 mg, 0.72 mmol) in
MeOH (10 mL) at rt for 5 min. Then, the reaction mixture
was stirred at reflux for 20 h. The reaction mixture was
cooled to rt and the solvent was concentrated. The residue
was diluted with water (10 mL) and the mixture was
extracted with CH2Cl2 (3 x 20 mL). The combined organic
layers were washed with brine, dried, filtered and
evaporated to afford crude product. Purification on silica
gel (hexanes/EtOAc = 8/1~1/1) afforded 5n. Yield = 65%
(175 mg). Then, boron trifluoride etherate (142 mg, 1.0
mmol) was added to a solution of the resulting product 5n
(175 mg, 0.47 mmol) in MeOH (10 mL) at rt for 5 min.
Then, the reaction mixture was stirred at reflux for 20 h.
The reaction mixture was cooled to rt and the solvent was
concentrated. The residue was diluted with water (10 mL)
and the mixture was extracted with CH2Cl2 (3 x 20 mL).
The combined organic layers were washed with brine, dried,
filtered and evaporated to afford crude product. Purification
on silica gel (hexanes/EtOAc = 8/1~1/1) afforded 6n. Yield
= 60% (109 mg); Colorless gum; IR (CHCl3): 3069, 1735,
1458, 1108 cm–1; HRMS (ESI, M++1) calcd for C21H25O5S
5-(4-Methoxyphenyl)-5-phenyl-4-(toluene-4-
sulfonyl)pentanoic acid methyl ester (7a). Yield = 70%
o
(158 mg); Colorless solid; mp = 184-185 C (recrystallized
from hexanes and EtOAc); d.e. > 95%; IR (CHCl3): 3080,
1748, 1481, 1125 cm–1; HRMS (ESI, M++1) calcd for
C26H29O5S 453.1736, found 453.1739; 1H NMR (400 MHz,
CDCl3): δ 7.31 (d, J = 8.0 Hz, 2H), 7.25-7.21 (m, 3H),
7.17-7.13 (m, 1H), 7.04 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.8
Hz, 2H), 6.49 (d, J = 8.8 Hz, 2H), 4.37 (d, J = 10.4 Hz, 1H),
4.25-4.20 (m, 1H), 3.68 (s, 3H), 3.61 (s, 3H), 2.75-2.67 (m,
1H), 2.54-2.46 (m, 2H), 2.35 (s, 3H), 2.24-2.18 (m, 2H);
13C NMR (100 MHz, CDCl3): δ 173.10, 158.22, 143.28,
141.45, 137.40, 132.88, 129.13 (4x), 128.87 (2x), 128.00
(2x), 127.81 (2x), 126.93, 113.62 (2x), 66.52, 55.06, 51.56,
51.28, 31.08, 22.83, 21.44. Single-crystal X-Ray diagram:
crystal of compound 7a was grown by slow diffusion of
EtOAc into a solution of compound 7a in CH2Cl2 to yield
colorless prisms. The compound crystallizes in the
monoclinic crystal system, space group P 21/n, a =
10.7022(5) Å, b = 11.1193(5) Å, c = 20.3355(9) Å, V =
2383.65(19) Å3, Z = 4, dcalcd= 1.261 g/cm3, F(000) = 960,
2θ range 2.022 to 26.381o, R indices (all data) R1 = 0.0813,
wR2 = 0.2101.
5,5-Bis-(4-methoxyphenyl)-4-(toluene-4-sulfonyl)pentanoic
acid methyl ester (7b). Yield = 67% (161 mg); Colorless
o
solid; mp = 123-124 C (recrystallized from hexanes and
EtOAc); IR (CHCl3): 3087, 1752, 1482, 1130 cm–1; HRMS
(ESI, M++1) calcd for C27H31O6S 483.1841, found
1
483.1845; H NMR (400 MHz, CDCl3): δ 7.31 (d, J = 8.4
Hz, 2H), 7.13 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H),
6.93 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 6.49 (d, J
= 8.8 Hz, 2H), 4.34 (d, J = 10.0 Hz, 1H), 4.20-4.15 (m, 1H),
3.71 (s, 3H), 3.67 (s, 3H), 3.60 (s, 3H), 2.73-2.65 (m, 1H),
2.54-2.46 (m, 1H), 2.33 (s, 3H), 2.23-2.18 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ 173.03, 158.25, 158.05, 143.21,
137.27, 133.41, 133.25, 129.06 (2x), 128.99 (2x), 128.91
1
389.1423, found 389.1430; H NMR (400 MHz, CDCl3): δ
7.83 (s, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.8 Hz,
2H), 7.31 (d, J = 8.0 Hz, 2H), 7.91 (d, J = 8.8 Hz, 2H), 3.81
(s, 3H), 3.56 (s, 3H), 2.95-2.86 (m, 2H), 2.74-2.67 (m, 1H),
2.41 (s, 3H), 1.02 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ 175.83, 160.57, 144.06, 139.55, 136.89, 136.82,

ACCEPTED MANUSCRIPT
Tetrahedron
9
(2x), 127.75 (2x), 114.11 (2x), 113.55 (2x), 66.63, 55.04,
54.97, 51.47, 50.23, 31.03, 22.69, 21.35.
3058, 2985, 1138, 978 cm–1; HRMS (ESI, M++1) calcd for
C15H15O2S 259.0793, found 259.0796; 1H NMR (400 MHz,
CDCl3): δ 7.82 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 15.2 Hz,
1H), 7.48-7.45 (m, 2H), 7.40-7.37 (m, 3H), 7.33 (d, J = 8.4
Hz, 2H), 6.85 (d, J = 15.2 Hz, 1H), 2.42 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 144.32, 141.85, 137.70, 132.38,
131.03, 129.90 (2x), 128.99 (2x), 128.44 (2x), 127.63 (2x),
127.59, 21.53.
1,5-Bis-(4-methoxyphenyl)-4-(toluene-4-sulfonyl)pent-4-en-
1-one (8a). NaOH (100 mg, 2.5 mmol) in H2O (2.5 mL)
was added to a solution of 7b (96 mg, 0.2 mmol) in THF
(10 mL) at rt for 20 min. Then, the reaction mixture was
stirred at reflux for 20 h. The reaction mixture was cooled
to rt and the solvent was concentrated. The residue was
diluted with 2N H2SO4 (10 mL) and the mixture was
extracted with CH2Cl2 (3 x 20 mL). The combined organic
layers were washed with brine, dried, filtered and
evaporated to afford crude product. Without further
purification, SOCl2 (5 mL) was added to a solution of the
1-(Methane-4-sulfonyl)-2-phenylethylene (10b).32 Yield =
70% (64 mg); Colorless gum; IR (CHCl3): 3056, 2988,
1148, 995 cm–1; HRMS (ESI, M++1) calcd for C9H11O2S
1
183.0480, found 183.0483; H NMR (400 MHz, CDCl3): δ
7.63 (d, J = 15.6 Hz, 1H), 7.54-7.51 (m, 2H), 7.46-7.41 (m,
3H), 6.92 (d, J = 15.6 Hz, 1H), 3.04 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 144.09, 132.02, 131.42, 129.17 (2x),
128.56 (2x), 126.06, 43.28.
o
resulting products at 0 C for 10 min. Then, the reaction
mixture was stirred at reflux for 20 h. The reaction mixture
was cooled to rt and the solvent was concentrated. Without
further purification, AlCl3 (133 mg, 1.0 mmol) was added
to a solution of the resulting product in CH2Cl2 (10 mL) at
0 oC for 10 min. Then, the reaction mixture was stirred at rt
for 20 h. The reaction mixture was concentrated. The
residue was diluted with water (10 mL) and the mixture
was extracted with CH2Cl2 (3 x 20 mL). The combined
organic layers were washed with brine, dried, filtered and
evaporated to afford crude product. Purification on silica
gel (hexanes/EtOAc = 8/1~1/1) afforded compound 8a.
Acknowledgments
The authors would like to thank the Ministry of Science
and Technology of the Republic of China for its financial
support (MOST 105-2113-M-037-001).
References and notes
o
(1) For reviews and books on the sulfone chemistry, see: (a) El-Awa, A.;
Noshi, M. N.; Mollat du Jourdin, X.; Fuchs, P. L. Chem. Rev. 2009,
109, 2315-2349. (b) Trost, B. M. Bull. Chem. Soc. Jpn. 1988, 61,
107-124. (c) Simpkins, N. S. Sulphones in Organic Synthesis;
Pergamon Press, Oxford, UK, 1993. (d) Patai, S.; Rappoport, Z.;
Stirling, C., Eds. The Chemistry of Sulphones and Sulphoxides;
Wiley: Chichester, UK, 1988. (e) Najera, C.; Yus, M. Tetrahedron
1999, 55, 10547-10658. (f) Nenajdenko, V. G.; Krasovskiy, A. L.;
Balenkova, E. S. Tetrahedron 2007, 63, 12481-12539.
(2) Recent preparations of functionalized sulfones, see: (a) Zhou, G.;
Ting, P. T.; Aslanian, R. G. Tetrahedron Lett. 2010, 51, 939-941. (b)
Pospisil, J.; Sato, H. J. Org. Chem. 2011, 76, 2269-2272. (c) Tsui, G.
C.; Glenadel, Q.; Lau, C.; Lautens, M. Org. Lett. 2011, 13, 208-211.
(d) Kumar, A.; Muthyala, M. K. Tetrahedron Lett. 2011, 52, 5368-
5371. (e) Sreedhar, B.; Rawat, V. S. Synlett 2012, 23, 413-417. (f)
Lu, Q.; Zhang, J.; Zhao, G.; Qi, Y.; Wang, H.; Lei, W. J. Am. Chem.
Soc. 2013, 135, 11481-11484. (g) Singh, A. K.; Chawla, A. K.;
Chawla, R.; Keshari, T.; Yadav, V. K.; Yadav, L. D. S. Org. Biomol.
Chem. 2014, 12, 8550-8554. (h) Chawla, R.; Singh, A. K.; Yadav, L.
D. S. Eur. J. Org. Chem. 2014, 10, 2032-2036. (i) Singh, A. K.;
Chawla, R.; Yadav, L. D. S. Tetrahedron Lett. 2014, 55, 4742-5745.
(j) Shi, X.; Ren, X.; Ren, Z.; Li, J.; Wang, Y.; Yang, S.; Gu, J.; Gao,
Q.; Huang, G. Eur. J. Org. Chem. 2014, 5083-5088. (k) Handa, S.;
Fennewald, J. C.; Lipshutz, B. H. Angew. Chem. Int. Ed. 2014, 53,
3432-3435. (l) Tang, X.; Huang, L.; Xu, Y.; Yang, J.; Wu, W.; Jiang,
H. Angew. Chem., Int. Ed. 2014, 53, 4205-4208. (m) Chang, M.-Y.;
Cheng, Y.-C. Org. Lett. 2015, 17, 5702-5705. (n) Yadav, V. K.;
Srivastava, V. P.; Yadav, L. D. Synlett 2016, 27, 427-431.
(3) Xuan, J.; Feng, Z.-J.; Chen, J. R.; Lu, L.-Q.; Xiao, W.-J. Chem. Eur.
J. 2014, 20, 3045-3049.
Yield = 65% (59 mg); Colorless solid; mp = 129-130 C
(recrystallized from hexanes and EtOAc); IR (CHCl3):
3057, 1758, 1467, 1038 cm–1; HRMS (ESI, M++1) calcd for
C26H27O5S 451.1579, found 451.1573; 1H NMR (400 MHz,
CDCl3): δ 7.89 (d, J = 8.8 Hz, 2H), 7.79 (s, 1H), 7.78 (d, J
= 8.0 Hz, 2H), 7.41 (d, J = 9.2 Hz, 2H), 7.30 (d, J = 8.0 Hz,
2H), 6.90 (d, J = 8.8 Hz, 4H), 3.84 (s, 3H), 3.78 (s, 3H),
3.29-3.25 (m, 2H), 2.90-2.85 (m, 2H), 2.39 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 196.99, 163.52, 160.68, 144.05,
137.76, 137.34, 136.29, 131.39 (2x), 130.23 (2x), 129.74
(2x), 129.20, 127.98 (2x), 125.57, 114.37 (2x), 113.60 (2x),
55.36, 55.21, 36.53, 21.83, 21.43.
A representative synthetic procedure of compounds 10a-b
is as follows: NaBH4 (100 mg, 3.0 mmol) was added to a
solution of β-ketosulfones 3a (137 mg, 0.5 mmol) or 3k (99
mg, 0.5 mmol) in MeOH (10 mL) at rt for 20 min. The
reaction mixture was concentrated. The residue was diluted
with water (10 mL) and the mixture was extracted with
CH2Cl2 (3 x 20 mL). The combined organic layers were
washed with brine, dried, filtered and evaporated to afford
crude product. Without further purification, boron
trifluoride etherate (284 mg, 2.0 mmol) was added to a
solution of the resulting products in CH2Cl2 (10 mL) at rt
for 20 h. The reaction mixture was concentrated. The
residue was diluted with water (10 mL) and the mixture
was extracted with CH2Cl2 (3 x 20 mL). The combined
organic layers were washed with brine, dried, filtered and
evaporated to afford crude products. Purification on silica
gel (hexanes/EtOAc = 8/1~1/1) afforded compounds 10a-b.
(4) (a) Pandey, G.; Vaitla, J. Org. Lett. 2015, 17, 4890-4893. (b)
Kuninobu, Y.; Matsuzaki, H.; Nishi, M.; Takai, K. Org. Lett. 2011,
13, 2959-2961.
(5) Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K. Synlett 2014, 25, 1739-
1744.
(6) Wang, Q.-G.; Zhou, Q.-Q.; Deng, J.-G.; Chen, Y.-C. Org. Lett. 2013,
15, 4786-4789.
(7) Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K. Tetrahedron 2014, 70,
8908-8913.
2-Phenyl-1-(toluene-4-sulfonyl)ethylene (10a).31 Yield =
76% (98 mg); Colorless solid; mp = 120-122 oC
(recrystallized from hexanes and EtOAc); IR (CHCl3):
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Paixao, M. W.; Luque, R.; Alves, D. Org. Lett. 2015, 17, 6206-6209.

ACCEPTED MANUSCRIPT
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Tetrahedron
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(30) CCDC 1455027 (7a) contains the supplementary crystallographic
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Supplementary Material
Experimental procedure and scanned photocopies of NMR
(CDCl3) spectral data were supported.
(25) For I2/TBHP, see: (a) Singh, R.; Allam, B. K.; Singh, N.; Kumari, K.;
Singh, S. K.; Singh, K. N. Org. Lett. 2015, 17, 2656-2659. For
PhI(OAc)2, see: (b) Luo, Z.; Fang, Y.; Zhao, Y.; Xu, X.; Feng, C.; Li,