Indium-promoted Conversion of Allylic Bromide to Alcohol Moiety and Synthesis of Pipermethystine Skeletons

Article abstract of DOI:10.1002/jccs.201600239

Dihydropyridone bromide (2) was converted to the corresponding alcohol (1) by reaction with indium in air or with indium followed by treatment with a sulfonyloxaziridine. The alcohol (1) was transformed in four steps to a phenylsulfone-substituted pipermethystine derivative (10). Reductive cleavage of the phenylsulfone did not yield the pipermethystine natural product. Several new pyridone derivatives were synthesized.

Full text of DOI:10.1002/jccs.201600239

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Indium-promoted Conversion of Allylic Bromide to Alcohol Moiety and Synthesis of
Pipermethystine Skeletons
*
Bo-Sian Liou and Shang-Shing Peter Chou
Department of Chemistry, Fu Jen Catholic University, New Taipei City 24205, Taiwan
(Received: June 29, 2016; Accepted: July 20, 2016; Published Online: August 30, 2016; DOI: 10.1002/jccs.201600239)
Dihydropyridone bromide (2) was converted to the corresponding alcohol (1) by reaction with
indium in air or with indium followed by treatment with a sulfonyloxaziridine. The alcohol (1)
was transformed in four steps to a phenylsulfone-substituted pipermethystine derivative (10).
Reductive cleavage of the phenylsulfone did not yield the pipermethystine natural product. Several
new pyridone derivatives were synthesized.
Keywords: Aza-Diels–Alder reactions; Pipermethystine synthesis; Organoindium reagents; Allylic
bromides.
2
INTRODUCTION
We had developed a new aza-Diels–Alder reaction
product 4 in good yield. Under this new reaction con-
dition, however, we found that compound 1 underwent
1
of phenylthio-substituted 3-sulfolenes with p-
toluenesulfonyl isocyanate (PTSI) to give the 2(1H)-
elimination of HBr to give 2-pyridone 5 in 61% yield.
Apparently, an alkyl group at C-6 is essential for the
substitution reaction. With no substituent at C-6, the
elimination reaction of compound 2 would be faster.
We also carried out the hydrolysis reaction of
1
pyridone derivatives, and used this method to synthe-
2
size several natural products. We now report our stud-
ies on the synthesis of pipermethystine, a natural
3
product isolated from the leaves of Piper methysticum.
compound 2 without the presence of Et N in order to
3
Only one total synthesis of pipermethystine has been
avoid the elimination product 5 (Table 1). In entry
4
reported. Its biological activities have also been stud-
1
, treatment of compound 2 with THF/H O (1/0.45) in
2
5
ied. A retrosynthetic analysis of our approach to the
ꢀ
a sealed tube at 70 C gave compound 1 (10%) and elim-
ination product 5 (2%) and recovered the starting mate-
synthesis of pipermethystine is shown in Scheme 1. We
envision that the desired natural product could be
obtained by selective desulfonylation of an intermediate
A, which would be easily accessible by the oxidation of
an intermediate B. Compound B could be obtained by
acylation of an intermediate C, which should be readily
available from the dihydropyridone precursor 1 we
rial 2 (70%). Increasing the reaction temperature to
ꢀ
1
2
5
20 C (entry 2) only gave the recovered compound
(96%). In entry 3, increasing the reaction time to
.5 days gave similar product yields as in entry 1. Treat-
ment of compound 2 with THF/HOAc (1/1) at 70 C
entry 4) or in a sealed tube at 120 C (entry 5) only
ꢀ
ꢀ
(
1
have previously prepared.
gave the recovered starting material 2. In entry 6, the
ꢀ
addition of NH OAc to THF/H O (1/0.45) at 70 C
4
2
RESULTS AND DISCUSSION
afforded a mixture of compound 1 (6%) and the elimi-
nation product 5 (40%) and recovered the starting
material 2 (53%); no OAc substitution product was
obtained. Since the highest reaction yield of compound
1 obtained from the hydrolysis condition (Table 1) was
only 10%, we wanted to investigate other synthetic
routes to compound 1.
Preparation of compound 1 by hydrolysis
Compound 1 was unexpectedly synthesized in our
1
previous work by the reaction of the bromide 2 with
sodium nitrite (Scheme 2), but the yield was only 13%.
Subsequently, we developed a hydrolysis reaction of
compounds 3 bearing a substituent at C-6 to give
*Corresponding author. Email: 002181@mail.fju.edu.tw
8
18
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JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Synthesis of Pipermethystine Skeletons
Preparation of compound 1 by organometallic reactions
Our second approach to synthesize compound
6
1
from the bromide 2 was to use a suitable metal to
give an organometallic intermediate, which could then
7–10
11,12
react with air
or other oxidants
to afford the
desired product 1 (Scheme 3). Since compound 2 has
carbonyl and tosyl groups that might react with the
organometallic reagent, we decided to use less reactive
metals. After some preliminary tests we found that
indium metal was quite suitable for this type of
Scheme 1. Retrosynthetic analysis of pipermethystine.
6
reaction.
We carried out systematic studies of the reaction
conditions (Table 2). In entry 1, treatment of compound
ꢀ
2
with 2 equiv of indium at 70 C in a sealed tube
(
in air) in THF for 2 days afforded compound 1 (20%),
1
elimination product 5 (7%), and reduction product 6
72%). However, if 0.2 equiv of indium was used (entry
), the yield of compound 1 decreased significantly and
(
2
large amounts of recovered starting material 2 were also
obtained. We also tried the reaction of compound 2 with
indium in THF with 2.5 bar of O in a pressurized cyl-
2
inder at room temperature. However, only the starting
material 2 was recovered. It is speculated that the high
pressure of O might have oxidized the indium metal so
2
that the metal insertion did not occur.
We propose a plausible mechanism for the forma-
10
tion of compound 1 in Scheme 4. Indium insertion
into the C–Br bond would give an organoindium inter-
mediate D, which would then react with air to give an
organoperoxide E. Further reaction of E with another
molecule of the indium intermediate D would yield two
molecules of an alkoxide intermediate F. Aqueous
Scheme 2. Previous preparation of compound 1 and
derivatives.
Table 1. Preparation of compound 1 by hydrolysis
Entry
Reaction conditions
Results (% yield)
ꢀ
1
2
3
4
5
6
THF/H O (1/0.45), sealed tube, 70 C, 24 h
1 (10), 5 (2), 2 (70)
2 (96)
1 (6), 5 (5), 2 (65)
2 (100)
2 (80)
1 (6), 5 (40), 2 (53)
2
ꢀ
THF/H
THF/H
THF/HOAc (1/1), 70 C, 24 h
2
O (1/0.45), sealed tube, 120 C, 24 h
ꢀ
2
O (1/0.45), sealed tube, 70 C, 5.5 day
ꢀ
ꢀ
THF/HOAc (1/1), sealed tube, 120 C, 24 h
THF/H O (1/0.45), NH OAc (3 equiv), sealed tube, 70 C, 24 h
ꢀ
2
4
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Article
Liou and Chou
Scheme 3. Proposed preparation of compound 1 by
organometallic reagents.
work-up would then give compound 1.
We also used (−)-(2S,8aR)-(camphorylsulfonyl)
11
oxaziridine as the oxidant (Table 2, entries 3 and 4).
Treatment of compound 2 with 2 equiv of indium and
1.2 equiv of oxaziridine (entry 3) afforded compound
1
(22%) and recovered compound 2 (42%). Increasing
Scheme 4. A plausible mechanism for the formation
the amount of indium and oxaziridine (entry 4) gave
compound 1 (29%), elimination product 5 (4%), and
recovered compound 2 (15%). So far, the highest yield
of compound 1 from bromide 2 was 29%.
of compound 1 by reaction of bromide
2 with indium in air.
Synthesis of pipermethystine skeletons
We synthesized the pipermethystine skeleton, as
shown in Scheme 5. The N-tosyl group of compound
1
was cleaved by Parsons’ method (Bu SnH/AIBN) to
3
1
3
give compound 7. Concentrations of Bu SnH and
3
compound 1 were both kept at 0.05 M; lower concen-
trations led to large amounts of unreacted starting
material 1. Reaction of compound 7 with Ac O and
2
Et N in CH Cl for 2 days provided compound 8 in
3
2
2
high yield; the reaction was rather slow, probably
Scheme 5. Synthesis of the pipermethystine skele-
tons 9.
because of the low solubility of compound 7 in CH Cl .
2
2
Compound 9 was obtained in 80% yield by the reaction
of compound 8 with hydrocinnamoyl chloride in the
presence of Et N and
4
a
catalytic amount of
-dimethylaminopyridine (DMAP) in refluxing 1,2-
dichloroethane.
3
Table 2. Preparation of compound 1 by reaction with indium
a
Entry Reaction conditions
Results (% yield)
ꢀ
1
2
In (2 equiv), THF, air, 70 C, sealed tube, 2 day
1 (20), 5 (7), 6 (72)
1 (7), 5 (6), 6 (14),
ꢀ
In (0.2 equiv), THF, air, 70 C, sealed tube, 2 day
2
(51)
3
In (2 equiv), (−)-(2S,8aR)-(Camphorylsulfonyl)oxazirdine (1.2 equiv), THF, sealed tube,
1 (22), 2 (42)
ꢀ
7
0 C, 2 day
4
In (4 equiv), (−)-(2S,8aR)-(Camphorylsulfonyl)oxazirdine (2.4 equiv), THF, sealed tube,
1 (29), 5 (4), 2 (15)
ꢀ
7
0 C, 2 day
a
3
In the eluent of chromatography 2–5% of Et N was added.
8
20
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Synthesis of Pipermethystine Skeletons
Oxidation of sulfides to sulfones and desulfonylation
Compound 9 was oxidized by mCPBA to give the
sulfone 10 in 25% yield (Scheme 6); the low yield of
compound 10 was probably due to its instability even
in air at room temperature. Attempted desulfonylaion
of compound 10 with 5% Na/Hg and a small amount
of H PO in refluxing THF did not give the desired nat-
3
4
4
ural product, pipermethystine. Instead, hydrocinna-
moyl acid was obtained, probably by cleaving the
N-acyl group under the reaction condition. Crude
4
Scheme 7. Preparation and desulfonylation of sul-
1
H-NMR data indicated that the OAc group of com-
fone 12.
pound 10 was also removed. We also used Al/Hg for
1
4
or basic condition did not yield effectively the desired
alcohol 1 due to the dominant elimination reaction. We
developed a new and more effective method for the
preparation of compound 1 by the reaction of bromide
the desulfonylation reaction,
which gave silmilar
results as Na/Hg. Since compound 10 decomposes too
easily, we decided to use the sulfone 11, obtained in
54% yield from the oxidation of compound 8 with
2
with indium in air or with indium followed by treat-
ment with (camphorylsulfonyl)oxaziridine. Compound
was converted in four steps to the sulfone-substituted
mCPBA, for the desulfonylation reaction. Unfortu-
nately, treatment of compound 11 with Al/Hg also
cleaved the OAc group. From these results, it seemed
that the OAc group in compounds 10 and 11 was too
labile to survive the reductive condition.
1
pipermethystine structure 10. Intended reductive cleav-
age of the phenylsulfonyl group of compound 10 did
not give the desired natural product pipermethystine
because of the presence of a reactive allylic acetate
group. We have also synthesized several new pyridone
derivatives, the biological activities of which will be
studied in future.
We further studied the desulfonylation of com-
pounds without an OAc group at C-6, as shown in
Scheme 7. Treatment compound 1 with mCPBA gave
the sulfone 12, which underwent the desulfonylation
ꢀ
with Al/Hg in THF at 0 C to give the desired product
13 together with the over-reduction product 14 in the
ratio 1:0.2 (94% yield). Unfortunately, these two com-
pounds could not be separated by column chromatogra-
phy. It should be noted that if the reaction of
compound 12 with Al/Hg was carried out at room tem-
perature, the ratio of compounds 13:14 was 1:4.7. Thus,
compound 14 was obtained by further reduction of
compound 13 by Al/Hg.
EXPERIMENTAL
Melting points were determined with an SMP3
melting apparatus. Infrared (IR) spectra (attenuated
total reflection; ATR) were recorded with a Perkin
Elmer 100 series Fourier transform IR (FTIR) spectro-
1
13
photometer. H and C nuclear magnetic resonance
(NMR) spectra were mostly recorded on a Bruker
Avance 300 spectrometer operating at 300 and at
75 MHz, respectively. Chemical shifts (δ) are reported
in parts per million (ppm) and the coupling constants
In conclusion, we discovered that the hydrolysis of
bromide 2 bearing no substituent at C-6 under neutral
(
(
J) are given in hertz. High-resolution mass spectra
HRMS) were measured with a Finnigan/Thermo Quest
MAT 95XL mass spectrometer. Column chromato-
graphic purifications were performed using Merck silica
gel 60 (40–60 mm).
4
-(Phenylthio)-1-tosyl-1H-pyridin-2-one (5).
A
solution of 2 (50 mg, 0.115 mmol) in THF/Et N/H O
3
2
ꢀ
(
1 mL/0.3 mL/0.45 mL) was heated at 70 C for 24 h.
Scheme 6. Preparation and attempted desulfonyla-
After cooling, ethyl acetate (30 mL) was added and the
mixture washed with brine (30 mL × 2), dried
tion of sulfones 10 and 11.
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Article
Liou and Chou
(
MgSO ), and evaporated under vacuum. The crude
0.372 mmol) and AIBN (30.5 mg, 0.186 mmol) in tolu-
ene (11.2 mL). After addition, the mixture was heated
at reflux for 4 h, and the residue was evaporated under
vacuum. The crude product was purified by column
chromatography using ethyl acetate containing 10%
MeOH as eluent to give product 7 (41.6 mg, 61%) as a
4
product was purified by column chromatography (ethyl
acetate/hexane 1:3) to give product 5 (24.9 mg, 61%).
1
General procedure for the preparation of compound 1 by
hydrolysis (Table 1)
A solution of compound 2 (50 mg, 0.114 mmol) in
ꢀ
white solid: mp 181–184 C, (recryst. MeOH); IR (film,
THF/H O (1 mL/0.45 mL) was heated in a sealed tube
at 70 C for 24 h. The solvent was then removed under
vacuum, and the crude product was purified by column
chromatography (ethyl acetate/hexane 1:3 containing
2
5
−1
2
cm ): v 3306, 2955, 2924, 2854, 1645, 1464, 1396,
ꢀ
1
1
3
292, 1137, 1076, 960, 844, 812; H NMR (CDCl ,
3
00 MHz, ppm): δ 7.63–7.53 (2H, m), 7.49–7.28 (3H,
m), 5.46 (1H, s), 5.29 (1H, J = 2.1 Hz), 4.36 (1H, t,
–5% Et N) to give product 1 (4.1 mg, 10%), product
3
J = 4.5 Hz), 3.67 (1H, ddd, J = 13.2, 4.5, 2.1 Hz), 3.55
1
(1.0 mg, 2%), and product 2 (34.8 mg, 70%).
13
(
1H, ddd, J = 13.2, 4.5, 3.6 Hz); C NMR (methanol-
d4, 75 MHz, ppm): δ 165.4, 160.8, 135.2, 129.8, 129.7,
28.3, 113.1, 64.8, 46.2; FAB-MS (relative intensity):
General procedure for the preparation of compounds
1
1
and 6 by organometallic reactions (Table 2, entry 1)
+
m/z 222 (M +H, 9), 207 (19), 166 (11), 154 (22); Exact
A mixture of compound 2 (50 mg, 0.114 mmol)
+
mass Calcd for C H NO S (M ) 221.0510, FAB-
11
11
2
and indium (26.0 mg, 0.228 mmol) in THF (2 mL) was
ꢀ
HRMS m/z 221.0515.
-Acetoxy-4-(phenylthio)-5,6-dihydro-1H-pyridin-2-
one (8). mixture of compound (35.4 mg,
.160 mmol), Et N (0.112 mL) and acetic anhydride
heated in sealed tube at 70 C for 24 h. Ethyl acetate
5
(10 mL) was added and the reaction was quenched with
A
7
1% HCl aqueous solution. The aqueous solution was
0
3
extracted with ethyl acetate (30 mL × 3), and the
(
0
0.038 mL, 0.4 mmol) in dried CH Cl was mixed at
C and then stirred at room temperature for 2 days.
2 2
organic solution was dried (MgSO ) and concentrated
4
ꢀ
under vacuum. The crude product was purified by col-
Ethyl acetate (10 mL) was added and the reaction was
quenched with saturated sodium bicarbonate (10 mL),
and the aqueous solution was extracted with ethyl ace-
tate (30 mL × 3). The combined organic layers were
umn chromatography (ethyl acetate/hexane 1:3 contain-
1
ing 2—5% Et N) to give compounds 1 (8.6 mg, 20%),
3
1
1
6
(29.8 mg, 72%), and 5 (3.2 mg, 7%).
General procedure for the preparation of compound 1 by
dried (MgSO ) and concentrated under vacuum. The
4
organometallic reactions with (−)-(2S,8aR)-
crude product was purified by column chromatography
(
Camphorylsulfonyl)oxaziridine (Table 2, entry 4)
using ethyl acetate/hexane (2:1) as eluent to give prod-
ꢀ
A mixture of compound 2 (50 mg, 0.114 mmol),
uct 8 (37.9 mg, 90%) as a white solid: mp 142–144 C,
−1
indium (52.0 mg, 0.456 mmol), and (−)-(2S,8aR)-(cam-
phorylsulfonyl)oxaziridine (52.3 mg, 0.228 mmol) in
THF (2 mL) was heated in a sealed tube at 70 C for
(recryst. ethyl acetate); IR (neat, cm ): v 3054, 2987,
1
2305, 1741, 1666, 1604, 1551, 1421, 1265, 896; H
ꢀ
NMR (CDCl , 300 MHz, ppm): δ 7.54–7.51 (2H, m),
3
2
4 h. Ethyl acetate (10 mL) was added and the reaction
7.47–7.43 (3H, m), 5.93 (1H, s), 5.47 (1H, t,
J = 4.2 Hz), 5.41 (1H, d, J = 1.2 Hz), 3.70 (1H, dd,
J = 13.8, 4.2 Hz), 3.54 (1H, m), 2.16 (3H, s); C NMR
was quenched with 1% HCl aqueous solution. The
aqueous solution was extracted with EtOAc (30 mL ×
13
3), and the combined organic layers were dried
(CDCl , 75 MHz, ppm): δ 170.2, 164.2, 153.0, 135.5,
3
(
MgSO ) and concentrated under vacuum. The crude
130.3, 130.1, 127.3, 117.7, 65.6, 44.3, 20.9; FAB-MS
(relative intensity): m/z 264 (M +H, 43), 204 (43),
4
+
product was purified by column chromatography (ethyl
acetate/hexane 1:3 containing 2–5% Et N) to give com-
95 (29), 69 (60), 55 (100); Exact mass Calcd for
3
+
pounds 1 (12.5 mg, 29%), 5 (1.8 mg, 4%), and
C H NO S (M ) 263.0616, FAB-HRMS m/z
13
13
3
1
2
(7.6 mg, 15%).
263.0622.
5
-Hydroxy-4-(phenylthio)-5,6-dihydro-1H-pyridin-
5-Acetoxy-1-(3-phenylpropanoyl)-4-(phenylthio)-
5,6-dihydro-1H-pyridin-2-one (9). To a solution of com-
pound 8 (38.3 mg, 0.146 mmol) and DMAP (1.8 mg,
0.014 mmol) in 1,2-dichloroethane (2 mL) at room
2
0
-one (7). To a solution of compound 2 (116.5 mg,
.310 mmol) in degassed toluene (6.2 mL) was slowly
added dropwise (1 drop per second) Bu SnH (0.10 mL,
3
8
22
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JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Synthesis of Pipermethystine Skeletons
temperature under nitrogen were added sequentially
5-Acetoxy-4-(phenylsulfonyl)-5,6-dihydro-1H-pyri-
din-2-one (11). Compound 8 (9.5 mg, 0.036 mmol) with
3 equiv mCPBA gave compound 11 (5.7 mg 54%) as a
with a syringe Et N (0.10 mL, 0.73 mmol) and hydro-
3
cinnamoyl chloride (0.65 mL, 0.438 mmol). The reac-
tion mixture was refluxed for 24 h, and then the solvent
was removed under vacuum. Ethyl acetate (10 mL) was
added, and the organic solution was washed with 5%
HCl (10 mL) and saturated NaHCO3 (10 mL). The
organic solution was separated, and the aqueous solu-
tion was extracted with ethyl acetate (30 mL × 3), dried
ꢀ
white solid: mp 206–207 C, (recryst. ethyl acetate); IR
−1
(neat, cm ): v 3054, 2987, 2686, 2411, 2306, 1750, 1688,
1
1422, 1265, 1160, 896; H NMR (CDCl , 300 MHz,
3
ppm): δ 7.92–7.90 (2H, m), 7.74–7.69 (1H, m), 7.63–7.58
(2H, m), 7.05 (1H, d, J = 1.5 Hz), 6.43 (1H, s), 5.77 (1H,
s), 3.69 (1H, dd, J = 15, 3.3 Hz), 3.57–3.54 (1H, m), 1.68
13
(
MgSO ), and evaporated. The crude product was puri-
(3H,s); C NMR (CDCl , 75 MHz, ppm): δ 169.4, 162.4,
4
3
fied by column chromatography using ethyl acetate/hex-
ane (1:5) as eluent to give compound 9 (46.4 mg, 51%)
as a yellow oil; IR (neat, cm ): v 3054, 2987, 2930,
147.7, 138.0, 134.6, 132.4, 129.6, 128.9, 60.1, 45.5, 20.3.
5-Hydroxy-4-(phenylsulfonyl)-1-tosyl-5,6-dihydro-
−1
1H-pyridin-2-one
(12).
Compound
2
(70 mg,
2
8
855, 2305, 1746, 1682, 1603, 1421, 1265, 1078, 1043,
0.186 mmol) with 3 equiv mCPBA gave compound 12
1
ꢀ
96; H NMR (CDCl , 300 MHz, ppm): δ 7.64–7.45
(43.2 mg 57%) as a white solid: mp 143—146 C, (recryst.
3
−1
(
5
5H, m), 7.43–7.00 (5H, m), 5.76 (1H, t, J = 4.2 Hz),
.37 (1H, s), 4.47 (1H, dd, J = 14.4, 4.2 Hz), 3.76 (1H,
dd, J = 14.4, 3.6 Hz), 3.32–3.14 (2H, m), 3.00–2.94
ethyl acetate); IR (neat, cm ): v 3301, 3054 , 2987, 2685,
1
2521, 2305, 1697, 1551, 1265, 1156, 896; H NMR
(CDCl , 300 MHz, ppm): δ 7.93–7.91 (4H, m), 7.83–7.72
3
1
3
(2H, m), 2.12 (3H, s); C NMR (CDCl , 75 MHz,
(1H, m), 7.64–7.56 (2H, m), 7.33–7.31 (2H, m), 6.35 (1H,
s), 4.71–4.64 (2H, m), 3.73 (1H, dd, J = 13.8, 3 Hz), 3.00
3
ppm): δ 175.3, 169.7, 162.6, 157.3, 141.0, 135.4, 130.6,
13
1
3
3
1
3
30.2, 128.5, 128.3, 126.9, 126.0, 118.0, 65.0, 45.3, 40.5,
(1H, s), 2.43 (3H, s); C NMR (CDCl , 75 MHz, ppm):
3
0.9, 20.8; FAB-MS (relative intensity): m/z
δ 159.7, 153.1, 145.6, 136.8, 135.1, 134.8, 133.6, 129.8,
129.5, 129.0, 128.8, 60.4, 50.5, 21.7.
+
96 (M +H, 0.83), 376 (1), 342 (1), 249 (20), 228, (45),
+
66 (30); Exact mass Calcd for C H NO S (M )
2
2
21
4
15
General preparation of Al/Hg reagent
95.1191, FAB-HRMS m/z 395.1195.
An aluminum foil was cut to the size 2 × 1 cm
(
1
10 mg), put it in 5% NaOH aqueous solution for
min, and then washed by distilled water quickly. The
General procedure for oxidation with mCPBA
To a solution of the sulfide (0.068 mmol) in
washed aluminum foil was put in 5% HgCl aqueous
2
CH Cl2 (2 mL) in an ice bath was added mCPBA
2
solution for 1 min, followed by washing with distilled
water, ethanol, and ether.
(
70–75% in H O, 0.17 mmol). After 5 min, the ice bath
2
was removed, and the mixture was further stirred at
room temperature for 2 h. To the reaction mixture was
then added successively saturated Na S O (10 mL)
and saturated NaHCO3 (10 mL), and was extracted
with CH Cl (20 × 3 mL). The organic solution was
5
-Hydroxy-1-tosyl-5,6-dihydro-1H-pyridin-2-one
(
13) and 5-Hydroxy-1-tosylpiperidin-2-one (14). A mix-
2
2
3
ture of compound 12 (5 mg, 0.0123 mmol), Al/Hg
ꢀ
(
10 mg, 0.370 mmol) in THF (1 mL) was stirred at 0 C
2
2
for 1 day. Ethyl acetate (10 mL) was added, and the
organic solution was filtered through a flash column of
celite. The filtered solution was evaporated under vac-
uum. The crude product was purified by column chro-
matography using ethyl acetate/hexane (1:1) containing
dried over MgSO and evaporated. The crude product
was purified by column chromatography (ethyl acetate
4
/
hexane 1:1 to 2:1) to give purified sulfone products.
-Acetoxy-1-(3-phenylpropanoyl)-4-(phenylsulfo-
nyl)-5,6-dihydro-1H-pyridin-2-one (10). Compound
(26.7 mg, 0.068 mmol) with 2.5 equiv mCPBA gave
5
2
–5% Et N as eluent to give compound 13 and com-
3
9
1
pound 14 in the ratio 1:0.2 (3.4 mg, 94%).
compound 10 (7.3 mg, 25%); H NMR (CDCl3,
00 MHz, ppm): δ 7.95–7.75 (2H, m), 7.79–7.70 (1H,
m), 7.69–7.58 (2H, m), 7.48–7.11 (5H, m), 7.07 (1H, s),
3
ACKNOWLEDGMENTS
5
2
.87 (1H, t, J = 2.7 Hz), 4.74 (1H, dd, J = 15.3,
.1 Hz), 3.43 (1H, dd, J = 15.3, 2.7 Hz), 3.94–3.16
Financial support of this work by the Ministry of
Science and Technology of the Republic of China (NSC
101-2113-M-030-001-MY2) is gratefully acknowledged.
(2H, m), 3.07–2.89 (2H, m), 1.60 (3H, s).
J. Chin. Chem. Soc. 2016, 63, 818–824
© 2016 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
823

Article
Liou and Chou
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© 2016 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2016, 63, 818–824