Sodium amalgam mediated desulfonylative reduction of α-functionalized β-ketosulfones

Article abstract of DOI:10.1016/j.tet.2016.07.043

Sodium amalgam mediated desulfonylative reduction of β-ketosulfones in MeOH at rt affords alcohols in good yields via radical desulfonylation of β-ketosulfones and sequential Bouveault-Blanc reduction of the resulting ketones.

Full text of DOI:10.1016/j.tet.2016.07.043

Tetrahedron xxx (2016) 1e9
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Sodium amalgam mediated desulfonylative reduction of
a-functionalized b-ketosulfones
*
Chieh-Kai Chan, Yi-Hsuan Huang, Meng-Yang Chang
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Sodium amalgam mediated desulfonylative reduction of b-ketosulfones in MeOH at rt affords alcohols in
Received 6 June 2016
Received in revised form 11 July 2016
Accepted 12 July 2016
Available online xxx
good yields via radical desulfonylation of
resulting ketones.
b
-ketosulfones and sequential Bouveault-Blanc reduction of the
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Sodium amalgam
b
-Ketosulfones
Desulfonylation
Alcohols
1. Introduction
sodium amalgam mediated cleavage of the carbonesulfur bonds. In
a typical desulfonylation of the -ketosulfone process, sodium
b
Functionalized
b
-ketosulfones are useful building blocks for the
amalgam was a preferred choice as an electron transfer reagent for
construction of diversified structural frameworks by using the
generating ketones in the presence of NH4Cl or Na2HPO4.18
versatile chemical transformations in modern organic synthesis.1,2
These skeletons include (i) acyclic diketones,3a
a
-methenyl keto-
O
R
O
Me
O
S
R
nes,3b,c and styrylsulfones,4a (ii) monocyclic sulfones,3d cyclo-
Ar
S
P
Ar
O
propanes,4b
triazoles,3e
pyrazoles,3f,g
dihydrofurans,3h,4e
Ar
O
n
Me
OBu
tetrahydrofurans,4c tetrahydropyrans,4d pyrroles,4f furans,4g,h are-
nes,4i and pyridazines,4j (iii) bicyclic benzosuberans,4k tetralins,4l
and naphthalenes,4m (iv) tricyclic phenanthrenes,4n and (v) tetra-
cyclic phenanthrofurans.4o A sulfonyl group bearing an electron-
HO
Ar
4c
MeO
P = styryl
OMe
this work
4n
4m
NaBH
then
P = aryl
photolysis
P = propargyl
4
Na/Hg
O
S
O
BF OEt
3
2
R
R
S
Me
Me
O
Me
Me
O
Ar
O
In(OTf)
then
NaBH
then
R
3
4
withdrawing substituent can stabilize the adjacent
a-carbanion,
α
P
S
Ar
N
O
thus facilitating the bond formation by alkylation, condensation,
annulation, rearrangement, and cross-coupling. However, the
usefulness of the sulfonyl group is dependent in most examples.
After having served the synthetic purpose, the subsequent removal
of the sulfonyl group (desulfonylation) from the molecules is often
observed.5 Several typical reducing agents have accomplished the
reductive desulfonylation, such as active metals, metals/metals,
N
Ar
N H
BF OEt
2
4
3 2
O
Ar
β
4j
P = propargyl
veratrole
Bi(OTf)
MeO
MeO
OMe
OMe
4k
2+
2+
4k
NaBH
then
mcpba
Pd /Cu
4
3
P = prenyl
P = allyl
NH OAc
4
O
R
O
O
Me
Me
R
S
HO
Ar
S
O
O
S
R
Ar
N
Ar
Me
O
Ar
O
Ar Me
Ar
metal/salts, or salts (Na/Hg, Al/Hg,6 Zn,7 Mg,8 SmI2, TiCl4/Sm,10
9
O
H
4d
4f
4h
4i
4i
P = cinnamyl
P = allyl
P = propargyl
P = gernayl
P = prenyl
b-ketosulfones.
HgCl2/Sm,11 TiCl4/Zn,12 Sm/HOAc,13 Bu3SnH,14 and CrCl315) and
Na2S2O4.16 Photolytic desulfonylation could also be realized with
ascorbic acid17a or Ru(II) complex.17b,c In our ongoing research
program on the formation of sulfonyl skeletons by functionalizing
Scheme 1. Recent synthetic applications of functionalized
the
b-ketosulfones (Scheme 1), we turned the synthetic aim to
However, in our cases, the unexpected alcohols replaced the
predicted ketones under sodium amalgam mediated desulfonyla-
tive reduction conditions. Under the standard conditions, we found
that the freshly prepared sodium amalgam could not only initiate
* Corresponding author. E-mail address: mychang@kmu.edu.tw (M.-Y. Chang).
http://dx.doi.org/10.1016/j.tet.2016.07.043
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
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2
C.-K. Chan et al. / Tetrahedron xxx (2016) 1e9
desulfonylation of
a sequential BouveaulteBlanc type reduction of in situ generated
a
-functionalized
b
-ketosulfones but also induce
Ph, Me; R1¼Ph, 4-FC6H4, 4-PhC6H4; R2¼H, Me), secondary alcohols
5aek were provided, as shown in entries 1e13.
ketone. To the best of our knowledge, no examples of a one-pot
For the sodium amalgam mediated reaction of 1e (Ar¼4-
CF3C6H4), 5e was isolated in a 53% yield along with a 30% yield of
5d (entry 5). From the observations, we envisioned that sodium
conversion from
b-ketosulfones 1e4 to alcohols 5e8 have been
reported (Scheme 2).
amalgam could promote the transformation from
a
4-
desulfonylation
Bouveault-Blanc type reduction
O
trifluoromethylphenyl group to a 4-methylphenyl group by the
reduction of benzylic trifluoro substituent. On the other hand, for
the sodium amalgam mediated reaction of 1f (Ar¼p-nitrophenyl),
we found that 5f having a 4-aminophenyl group was isolated in
a 56% yield along with a 16% yield of 5f-1 (entry 6). The results
showed that the reduction of the nitro group of 1f and retro-aldol
reaction of 1f occurred simultaneously under the reaction condi-
tions. In entry 7, reaction of 1g having a 3-nitro group also provided
a 76% yield of 5g under similar conditions. For uses of a lighter
loading sodium amalgam, treatment of 1a with 1% or 5% sodium
amalgam in MeOH (10 mL) for 10 h or 15 h was examined. However,
1% or 5% sodium amalgam provided lower yields of 5a (for 5%/10 h,
75%; for 1%/15 h, 60%). We envisioned that an elongating reaction
time should decrease the yield. A small volume of reaction solvent
(a concentrated solution) was tested. By the use of 5 mL of MeOH,
a lower yield of 5a (84%) was observed under the similar condition.
Based on the results, a possible reaction mechanism is believed
wherein the reaction proceeded via an electron-transfer process, as
shown in Scheme 3. The mechanism should be initiated to form
radical anion I by the involvement of a single electron of sodium,
and the release of a sulfinate radical could lead to enolate II. The
sulfinate radical should trap an electron to form sulfinic acid so-
dium salt. Furthermore, protonation of enolate II with MeOH gives
enol III. After in situ tautomerization of enol III produces ketone IV.
The following steps are similar to those of the BouveaulteBlanc
reduction.20,21 Then, a one electron transfer from the sodium to
carbonyl group of ketone IV produces another radical anion V. By
abstraction of a proton from MeOH, hydroxyl radical VI is gener-
ated. Finally, a single electron transfer of VI and protonation of the
resulting carbanion is able to afford 5a (Scheme 4).
O
O
S
OH
Na/Hg
MeOH
R
Ar
Ar
Ar
O
3
3
3
1
R
R
R
R
2
1
2
1
2
R
R
R
R
R
1-4
5-8
1, cinnamyl; 2, styryl; 3, allyl; 4, prenyl
Scheme 2. Desulfonylative reduction of b-ketosulfone with sodium amalgam.
2. Results and discussion
Although different percentages of sodium amalgam could be
commercially available for desulfonylation reactions, many organic
chemists still have a good habit of preparing fresh sodium amalgam
by themselves due to the convenience, instant supply, and cheaper
source.19 However, care should be exercised in the preparation of
sodium amalgam since the initial reaction is highly exothermic.
This step and all subsequent operations should be carried out in
a well-ventilated hood. Our method for 10% sodium amalgam is
described as follows: 10e15 pieces of sodium (3.0 g) were added
stepwise into the reaction mixture of mercury (30.0 g) and anhy-
drous toluene (30 mL) at rt in a wide-mouthed Erlenmeyer flask
(250 mL). The reaction mixture was stirred vigorously at 100 ꢀC for
10 min, cooled to rt for 15 min, and then filtrated with toluene to
provide crude sodium amalgam. Furthermore, by employing
freshly prepared 10% sodium amalgam, the desulfonylative re-
duction of model substrate 1a (Ar¼Ph, R¼Tol, R1¼Ph, R2¼H,
1.0 mmol) with 2 g of 10% sodium amalgam provided 5a in an 89%
yield in MeOH (10 mL) at rt for 2 h. Elongating the reaction time
(2/20 h), the yield was decreased to 68%. Examining the results,
we explored the substrate scope, and the results are shown in
Table 1. To adjust Ar, R, R1 and R2 groups of
a-cinnamyl b-keto-
0
Na
O
S
O
S
O
O
S
O
O
S
O
sulfones 1aem (Ar¼Ph, 4-FC6H4, 4-MeOC6H4, 4-MeC6H4, 4-
R
R
R
Na/Hg
MeOH
R
Ph
Ph
Ph
CF3C6H4, 4-NO2C6H4, 3-NO2C6H4, 4-PhC6H4, 2-naphthyl; R¼Tol,
O
O
O
O
Ph
Ph
Ph
MeOH
1a
I
II
Table 1
Reaction of 1aek with 10% sodium amalgama
O
O
S
OH
OH
O
S
0
OH
OH
O
O
OH
MeOH
Na
R
Na/Hg
MeOH
Ar
Ar
Tol
Ph
Ph
Ph
Ph
Ph
Ph
O
O
H N
2
2
1
2
1
R
R
R
R
Ph
Ph
Ph
Ph
Ph
Ph
5a
VI
V
IV
III
1
5
5f-1
5f, 4-NH
2
5g, 3-NH
2
Scheme 3. Plausible mechanism.
Entry
1, Ar¼, R¼, R1¼, R2¼
1a, Ph, Tol, Ph, H
5, Yield (%)b
1
2
3
4
5
6
7
8
5a, 89 (68)c
5b, 80
5c, 85
5d, 82
5e, 53d
5f, 56e
5g, 76
5h, 80
5i, 76
O
O
S
OH
1b, 4-FC6H4, Tol, Ph, H
1c, 4-MeOC6H4, Tol, Ph, H
1d, 4-MeC6H4, Tol, Ph, H
1e, 4-CF3C6H4, Tol, Ph, H
1f, 4-NO2C6H4, Tol, Ph, H
1g, 3-NO2C6H4, Tol, Ph, H
1h, 4-PhC6H4, Tol, Ph, H
1i, 2-naphthyl, Tol, Ph, H
1j, Ph, Ph, Ph, H
Na/Hg
MeOH
Tol
Ph
Ar
Ar
O
Ph
2a, Ar = Ph
2b, Ar = 4-FC H
2c, Ar = 4-MeOC H 2f, Ar = 2-naphthyl
2d, Ar = 4-MeC H
6a (83%) 6d (75%)
6b (86%) 6f (77%)
6c (80%) 6g (78%)
6
4
2e, Ar = 4-PhC H
6
4
6 4
6
4
9
Scheme 4. Reaction of 2aek with 10% sodium amalgam.
10
11
12
13
5a, 85
5a, 88
5j, 80
1k, Ph, Me, Ph, H
1l, Ph, Tol, 4-FC6H4, Me
1m, Ph, Tol, 4-PhC6H4, Me
5k, 76
For the aryl group with electron-donating or electron-
a
Reaction was run on 1 (1.0 mmol), Na(Hg) (10%, 2.0 g), MeOH (10 mL), 2 h.
Isolated yields.
20 h.
30% of 5d was isolated.
16% of 5f-1 was isolated.
withdrawing substituents (Ar¼Ph, 4-FC6H4, 4-MeOC6H4, 4-
b
c
MeC6H4, 4-PhC6H4, 2-naphthyl) on the
a-styryl b-ketosulfones
d
e
2aef, 6aef was provided in good yields (75e86%). For the side
a-
cinnamyl and -styryl groups of -ketosulfones 1 and 2, the
a
b
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C.-K. Chan et al. / Tetrahedron xxx (2016) 1e9
3
substituent effect of the aryl group on the vicinal and germinal
disubstituted olefins did not change the isolated yields of 5 and 6.
(R0¼n-C3H5), reduction of 12aef with sodium amalgam were ex-
amined, as shown in Scheme 8. The isolated yields (70e78%) of
13aef were similar to the above results via sodium amalgam me-
Changing the
a-substituent from cinnamyl and styryl to allyl
groups, 7aef was isolated in yields ranging from 70% to 78% via the
sodium amalgam mediated desulfonylation of 3aef, as shown in
Scheme 5. In particular, McMurry adducts 9aed could be isolated at
low (8e12%) yields under the above condition. Compared with
skeletons 1 and 2, only 3 provided minor amounts of vincinal diol 9
due to less-repulsion of side allyl arm. By a self-dimerization of the
proposed intermediate VI process, 9aef were generated in nearly
1:1 ratios. Although the isolated yields of 9aef were low, the results
could demonstrate a possible reaction pathway and intermediate.
The structure of 9c was determined by single-crystal X-ray
crystallography.22
diated desulfonylation. Treatment of monocyclic and bicyclic b-
ketosulfones 14aed with sodium amalgam in MeOH gave 15aed in
a range of 70e78% yields under the above condition (Scheme 9). In
particular, 15c-1 was isolated in an 8% yield via McMurry coupling.
The structure of 15c-1 was determined by single-crystal X-ray
crystallography.22
O
O
S
OH
Na/Hg
MeOH
Tol
Ar
Ar
O
R'
R'
12a, Ar = Ph, R' = Ph
12b, Ar = Ph, R' = 2-FC H
12c, Ar = Ph, R' = 3-MeOC H
13a (76%)
13b (78%)
13c (73%)
13d (70%)
13e (72%)
13f (77%)
6
4
O
O
S
OH
HO OH
Ar Ar
6
4
12d, Ar = Ph, R' = 2-naphthyl
12e, Ar = 4-FC H , R' = Ph
Na/Hg
MeOH
Tol
Ar
Ar
+
6
4
O
12f, Ar = Ph, R' = n-C H
3
5
Scheme 8. Reaction of 12 with 10% sodium amalgam.
3a, Ar = Ph
3b, Ar = 4-FC H
3c, Ar = 4-MeOC H
7a (72%)
7b (70%)
7c (73%)
7d (75%)
7e (78%)
7f (74%)
9a (12%)
9b (8%)
9c (10%)
9d (8%)
9e (ND)
9f (ND)
6
4
6
4
O
O
S
OH
3d, Ar = 4-MeC H
6
4
Na/Hg
MeOH
3e, Ar = 4-PhC H
6
4
Tol
3f, Ar = 2-naphthyl
O
( )
( )
n
n
Scheme 5. Reaction of 3 with 10% sodium amalgam.
14a, n = 1
14b, n = 2
15a (78%)
15b (70%)
In Scheme 6, for the freshly prepared sodium amalgam medi-
O
O
S
OH
HO
ated desulfonylation of
b-ketosulfones 4aee with a-prenyl, the a-
OH
Na/Hg
MeOH
Tol
geranyl or -farnesyl group produced 8aee in high yields
a
+
O
n
( )
( )
n
(84e86%). No influence was observed on the yield distribution
between 4d having a di-olefinic group and 4e having a tri-olefinic
14c, n = 1
14d, n = 2
15c (70%)
15d (76%)
15c-1 (8%)
15d-1 (ND)
group during the radical process. Furthermore, by adjusting
substituent from an olefinic motif to an alkynyl group, -propargyl
-ketosulfones 10aed (Ar¼Ph, 4-MeC6H4; Y¼H, Me, Et) were easily
converted to 11aed in high yields without the isolation of dimer
a-
Scheme 9. Reaction of 14 with 10% sodium amalgam.
a
b
products (Scheme 7). Changing the
a-substituent as aryl groups
To examine the applicability of this synthetic route, a formal
synthesis of sertraline (ZoloftÒ) was developed. Sertraline is a po-
tent selective serotonin reuptake inhibitor (SSRI), which has be-
come a popular synthetic target.23 For the formal synthesis of
sertraline, 14e was chosen as the starting material. As shown in
Scheme 10, sodium amalgam mediated reduction of 14e provided
15e in a 76% yield. Then, oxidation of 14e with PCC in the presence
of Celite afforded 16 in an 80% yield.24 1-Tetralone 16 is a key in-
(R0¼Ph, 2-FC6H4, 3-MeOC6H4, 2-naphthyl) and aliphatic group
O
O
S
OH
Na/Hg
MeOH
Tol
Me
Ar
Ar
O
Me
4a, Ar = Ph
4b, Ar = 4-FC H
Me
Me
8a (86%)
8b (85%)
8c (84%)
6
4
4c, Ar = 4-MeC H
termediate for the synthesis of sertraline. Finally, by removing
substituent,
were easily converted to 18aec in modest yields (71e80%), as
a-
6
4
b
-ketosulfones 17aec (Ar¼Ph, 4-FC6H4, 4-MeOC6H4)
O
O
S
OH
Me
Tol
Ph
Me
Me
Ph
Me
Me
Na/Hg
O
shown in Scheme 11.
MeOH
Me
4d
8d (85%)
Me
O
O
S
OH
O
HN
Me
Me
Me
Tol
Na/Hg
MeOH
PCC
O
O
S
OH
O
Me
Na/Hg
MeOH
Tol
Ph
Ph
CH Cl
2
2
O
Me
Me
Me
Me
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
4e
8e (86%)
14e
15e (76%)
16 (80%)
sertraline
Scheme 6. Reaction of 4 with 10% sodium amalgam.
Scheme 10. Formal synthesis of sertraline.
O
O
S
OH
Na/Hg
MeOH
Tol
Y
Ar
Ar
O
O
O
S
OH
Me
Na/Hg
MeOH
Tol
Ar
Ar
Y
O
10a, Ar = Ph, Y = H
10b, Ar = 4-MeC H , Y = H
10c, Ar = Ph, Y = Me
10d, Ar = Ph, Y = Et
11a (76%)
11b (70%)
11c (74%)
11d (73%)
17a, Ar = Ph
17b, Ar = 2-FC H
17c, Ar = 4-MeOC H
18a (80%)
18b (71%)
18c (73%)
6
4
6
4
6
4
Scheme 11. Reaction of 17 with 10% sodium amalgam.
Scheme 7. Reaction of 10 with 10% sodium amalgam.
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4
C.-K. Chan et al. / Tetrahedron xxx (2016) 1e9
3. Conclusion
7.25e7.21 (m, 1H), 6.91 (d, J¼8.8 Hz, 2H), 6.42 (d, J¼16.0 Hz, 1H), 6.25
(dt, J¼6.8, 16.0 Hz, 1H), 4.68 (dd, J¼6.4, 7.6 Hz, 1H), 3.81 (s, 3H),
In summary, we have developed a mild, facile and one-pot syn-
thesis of secondary benzylic alcohols in moderate to good yields via
2.35e2.23 (m, 3H), 2.03e1.96 (m, 1H), 1.90e1.84 (m, 1H); 13C NMR
(100 MHz, CDCl3): d 158.89,137.58,136.64,130.15,129.99,128.37 (2x),
sodium amalgam mediated desulfonylative reduction of
b-keto-
127.09 (2x),126.79,125.83 (2x),113.71 (2x), 73.38, 55.12, 38.23, 29.24.
sulfones in MeOH at rt under a one-pot process. The plausible mech-
anism of the BouveaulteBlanc type reduction has been discussed and
4.2.4. 5-Phenyl-1-p-tolylpent-4-en-1-ol (5d). Yield¼82% (207 mg);
Colorless oil; HRMS (ESI, Mþþ1) calcd for C18H21O 253.1592, found
proposed. Further investigation regarding synthetic applications of
ketosulfones will be conducted and published in due course.
b-
253.1593; 1H NMR (400 MHz, CDCl3):
d 7.37e7.18 (m, 10H), 6.42 (d,
J¼16.0 Hz,1H), 6.25 (dt, J¼6.8,16.0 Hz,1H), 4.71 (dd, J¼5.6, 7.6Hz,1H),
4. Experimental section
4.1. General
2.38 (s, 3H), 2.37e2.25 (m, 2H), 2.10e1.84 (m, 2H); 13C NMR
(100 MHz, CDCl3): d 141.54,137.63,137.21,130.25,130.03,129.11 (2x),
128.43 (2x),126.85,125.89 (2x),125.85 (2x), 73.76, 38.30, 29.27, 21.06.
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 nitrogen with
magnetic stirring. Products in organic solvents were dried with
anhydrous magnesium sulfate before concentration in vacuo.
Melting points were determined with a SMP3 melting apparatus.
1H and 13C NMR spectra were recorded on a Varian INOVA-400
spectrometer operating at 400/200 and at 100 MHz, respectively.
4.2.5. 5-Phenyl-1-(4-trifluoromethylphenyl)pent-4-en-1-ol
(5e). Yield¼53% (162 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd
for C18H18F3O 307.1310, found 307.1233; 1H NMR (400 MHz, CDCl3):
d
7.62 (d, J¼8.0 Hz, 2H), 7.48 (d, J¼8.0 Hz, 2H), 7.36e7.17 (m, 5H),
6.42 (d, J¼15.6 Hz, 1H), 6.22 (dt, J¼6.8, 15.6 Hz, 1H), 4.82 (dd, J¼5.2,
7.6 Hz, 1H), 2.36e2.27 (m, 2H), 2.02 (br s, 1H), 2.02e1.84 (m, 2H);
13C NMR (100 MHz, CDCl3):
d 148.50, 137.42, 130.72, 129.48, 129.17,
128.51 (2x), 127.06, 126.14 (2x), 125.94, 125.44 (d, J¼3.8 Hz, 2x),
Chemical shifts (d) are reported in parts per million (ppm) and the
125.36 (d, J¼3.8 Hz, 2x), 73.27, 38.55, 29.08.
coupling constants (J) are given in Hertz. High resolution mass
spectra (HRMS) were measured with a mass spectrometer Fin-
nigan/Thermo Quest MAT 95XL. X-ray crystal structures were ob-
tained with an Enraf-Nonius FR-590 diffractometer (CAD4, Kappa
CCD). Elemental analyses were carried out with Heraeus Vario III-
NCSH, Heraeus CHN-OS-Rapid Analyzer or Elementar Vario EL III.
4.2.6. 1-(4-Aminophenyl)-5-phenylpent-4-en-1-ol (5f). Yield¼56%
(142 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C17H20NO
254.1545, found 254.1551; 1H NMR (400 MHz, CDCl3):
d 7.35e7.27
(m, 4H), 7.22e7.18 (m, 1H), 7.15 (d, J¼8.4 Hz, 2H), 6.67 (d, J¼8.4 Hz,
2H), 6.39 (d, J¼16.0 Hz, 1H), 6.23 (dt, J¼6.8, 16.0 Hz, 1H), 4.61 (t,
J¼6.8 Hz, 1H), 2.95 (br s, 2H), 2.33e2.18 (m, 3H), 2.03e1.92 (m, 1H),
4.2. A representative synthetic procedure of skeleton 5 is as
follows
1.87e1.80 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 145.66, 137.70,
134.69, 130.19, 128.43 (2x), 127.45, 127.14 (2x), 126.83 (2x), 125.90
(2x), 115.16, 73.73, 38.13, 29.38.
Sodium amalgam (10%, 2.0 g) was added to a solution of skel-
eton 1 (1.0 mmol) in MeOH (10 mL) at rt. The reaction mixture was
stirred at rt for 2 h. The reaction mixture was filtrated and the
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3ꢁ20 mL). The
combined organic layers were washed with brine, dried, filtered
and evaporated to afford crude product under reduced pressure.
Purification on silica gel (hexanes/EtOAc¼8/1e4/1) afforded 5.
4.2.7. 1-Phenyl-4-(toluene-4-sulfonyl)but-1-ene (5f-1). Yield¼16%
(46 mg); Colorless solid; mp¼84e86 ꢀC (recrystallized from hex-
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C17H19O2S 287.1106,
found 287.1113; 1H NMR (400 MHz, CDCl3):
d
7.81 (d, J¼8.0 Hz, 2H),
7.35 (d, J¼8.0 Hz, 2H), 7.30e7.19 (m, 5H), 6.38 (d, J¼15.6 Hz, 1H),
6.03 (dt, J¼6.8, 15.6 Hz, 1H), 3.25e3.21 (m, 2H), 2.66e2.59 (m, 2H),
2.43 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 144.73, 136.65, 136.06,
132.31, 129.89 (2x), 128.48 (2x), 128.12 (2x), 127.47, 126.05 (2x),
125.18, 55.74, 26.38, 21.54.
4.2.1. 1,5-Diphenylpent-4-en-1-ol (5a). For Table 1, entry 1, 2 h:
Yield¼89% (212 mg); For entry 1, 20 h: Yield¼68% (162 mg); For
entry 10: Yield¼85% (202 mg); For entry 11: Yield¼88% (209 mg);
Colorless oil; HRMS (ESI, Mþþ1) calcd for C17H19O 239.1436, found
4.2.8. 1-(3-Aminophenyl)-5-phenylpent-4-en-1-ol (5g). Yield¼76%
(192 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C17H20NO
239.1438; 1H NMR (400 MHz, CDCl3):
d
7.41e7.30 (m, 9H), 7.24e7.22
254.1545, found 254.1542; 1H NMR (400 MHz, CDCl3):
d 7.35e7.11
(m, 1H), 6.44 (d, J¼8.0 Hz, 1H), 6.26 (dt, J¼7.2, 15.6 Hz, 1H), 4.74 (dd,
(m, 6H), 6.76e6.71 (m, 2H), 6.63e6.60 (m, 1H), 6.40 (d, J¼16.0 Hz,
1H), 6.22 (dt, J¼6.8,16.0 Hz,1H), 4.62 (dd, J¼6.0, 7.2 Hz,1H), 3.28 (br
s, 3H), 2.34e2.20 (m, 2H), 1.98e1.80 (m, 2H); 13C NMR (100 MHz,
J¼5.6, 7.2 Hz, 1H), 2.40e2.25 (m, 2H), 2.28 (br s, 1H), 2.06e1.88 (m,
2H); 13C NMR (100 MHz, CDCl3):
d 144.49, 137.57, 130.28, 129.93,
128.40 (4x), 127.49, 126.84, 125.86 (4x), 73.83, 38.34, 29.19.
CDCl3):
d 145.95, 145.85, 137.62, 130.21, 130.07, 129.32, 128.43 (2x),
126.84, 125.88 (2x), 116.62, 114.64, 112.83, 73.81, 38.21, 29.24.
4.2.2. 1-(4-Fluorophenyl)-5-phenylpent-4-en-1-ol (5b). Yield¼80%
(205 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C17H18FO
4.2.9. 1-Biphenyl-4-yl-5-phenylpent-4-en-1-ol
(5h). Yield¼80%
257.1342, found 257.1348; 1H NMR (400 MHz, CDCl3):
d
7.39e7.20
(251 mg); Colorless solid; mp¼75e77 ꢀC (recrystallized from hex-
(m, 7H), 7.08e7.02 (m, 2H), 6.41 (d, J¼16.0 Hz, 1H), 6.23 (dt, J¼6.8,
16.0 Hz, 1H), 4.72 (dd, J¼6.0, 8.0 Hz,1H), 2.33e2.23 (m, 2H), 2.07 (br
s, 1H), 2.02e1.93 (m, 1H), 1.90e1.81 (m, 1H); 13C NMR (100 MHz,
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C23H23O 315.1749,
found 315.1753; 1H NMR (400 MHz, CDCl3):
d 7.62e7.59 (m, 4H),
7.47e7.43 (m, 4H), 7.38e7.28 (m, 5H), 7.23e7.19 (m, 1H), 6.43 (d,
J¼15.6 Hz, 1H), 6.25 (dt, J¼6.8, 15.6 Hz, 1H), 4.80 (dd, J¼5.6, 12.0 Hz,
1H), 2.40e2.29 (m, 2H), 2.18e1.89 (m, 2H), 1.80 (br s, 1H); 13C NMR
CDCl3):
d
162.14 (d, J¼244.1 Hz), 140.23 (d, J¼2.2 Hz), 137.50, 130.47,
129.72, 128.47 (2x), 127.52 (d, J¼7.6 Hz, 2x), 126.96, 125.90 (2x),
115.24 (d, J¼21.2 Hz, 2x), 73.26, 38.48, 29.20.
(100 MHz, CDCl3):
d 143.54, 140.79, 140.58, 137.61, 130.45, 129.94,
128.76 (2x), 128.49 (2x), 127.28 (2x), 127.26 (2x), 127.06, 126.95,
126.37 (2x), 125.94 (2x), 73.75, 38.42, 29.30.
4 . 2 . 3 . 1 - ( 4 - M e t h o x y p h e nyl ) - 5 - p h e nyl p e n t - 4 - e n -1 -o l
(5c). Yield¼85% (228 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
18H21O2 269.1542, found 269.1546; 1H NMR (400 MHz, CDCl3):
4.2.10. 1-Naphthalen-2-yl-5-phenylpent-4-en-1-ol (5i). Yield¼76%
(219 mg); Colorless solid; mp¼70e71 ꢀC (recrystallized from
d
7.37 (d, J¼8.0 Hz, 2H), 7.34 (d, J¼8.0 Hz, 2H), 7.30 (d, J¼8.8 Hz, 2H),
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.07.043

C.-K. Chan et al. / Tetrahedron xxx (2016) 1e9
5
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C21H21O 289.1592,
148.02, 141.05, 136.67, 128.25 (2x), 127.34, 127.13 (2x), 126.08 (2x),
113.81 (2x), 112.43, 73.63, 55.24, 37.37, 31.56.
found 289.1593; 1H NMR (400 MHz, CDCl3):
d 7.88e7.85 (m, 3H),
7.81 (s, 1H), 7.54e7.49 (m, 3H), 7.38e7.31 (m, 4H), 7.26e7.22 (m,
1H), 6.43 (d, J¼15.6 Hz, 1H), 6.26 (dt, J¼6.4, 15.6 Hz, 1H), 4.90 (dd,
J¼6.4, 7.2 Hz, 1H), 2.40e2.27 (m, 2H), 2.23 (br s, 1H), 2.13e1.95 (m,
4.3.4. 4-Phenyl-1-p-tolylpent-4-en-1-ol (6d). Yield¼75% (189 mg);
Colorless oil; HRMS (ESI, Mþþ1) calcd for C18H21O 253.1592, found
2H); 13C NMR (100 MHz, CDCl3):
d
141.82, 137.57, 133.20, 132.94,
253.1596; 1H NMR (400 MHz, CDCl3):
d 7.40e7.37 (m, 2H),
130.39, 129.90, 128.44 (2x), 128.29, 127.87, 127.64, 126.89, 126.12,
125.90 (2x), 125.80, 124.63, 124.01, 74.01, 38.23, 29.24.
7.34e7.30 (m, 2H), 7.29e7.24 (m, 1H), 7.22 (d, J¼8.0 Hz, 2H), 7.16 (d,
J¼8.0 Hz, 2H), 5.30 (d, J¼1.2 Hz, 1H), 5.09 (d, J¼1.2 Hz, 1H), 4.68 (dd,
J¼5.6, 7.6 Hz, 1H), 2.70e2.62 (m, 1H), 2.57e2.49 (m, 1H), 2.35 (s,
4.2.11. 5-(4-Fluorophenyl)-1-phenylhex-4-en-1-ol (5j). Yield¼80%
(216 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C18H20FO
3H), 2.01e1.80 (m, 3H); 13C NMR (100 MHz, CDCl3):
d 148.03,141.54,
141.06, 137.24, 129.12 (2x), 128.26 (2x), 127.35, 126.08 (2x), 125.83
(2x), 112.45, 73.89, 37.39, 31.54, 21.07.
271.1498, found 271.1495; 1H NMR (400 MHz, CDCl3):
d 7.37 (br s,
2H), 7.36 (br s, 2H), 7.33e7.27 (m, 3H), 7.02e6.96 (m, 2H), 5.72 (t,
J¼7.2 Hz, 1H), 4.73 (dd, J¼5.6, 7.2 Hz, 1H), 2.33e2.22 (m, 2H),
4.3.5. 1-Biphenyl-4-yl-4-phenylpent-4-en-1-ol
(6e). Yield¼77%
2.05e1.82 (m, 3H), 1.98 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
161.18
(242 mg); Colorless solid; mp¼82e83 ꢀC (recrystallized from
(d, J¼243.4 Hz), 144.55, 134.42, 128.49 (2x), 127.61, 127.41 (d,
J¼3.0 Hz), 127.03 (d, J¼7.6 Hz, 2x), 125.89 (2x), 114.84 (d, J¼21.3 Hz,
2x), 74.17, 38.66, 29.68, 25.12, 15.94.
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C23H23O 315.1749,
found 315.1752; 1H NMR (400 MHz, CDCl3):
d 7.64e7.59 (m, 4H),
7.49e7.28 (m,10H), 5.35 (d, J¼1.2 Hz,1H), 5.16 (d, J¼1.2 Hz,1H), 4.78
(dd, J¼5.2, 7.6 Hz, 1H), 2.77e2.70 (m, 1H), 2.65e2.57 (m, 1H),
4.2.12. 5-Biphenyl-4-yl-1-phenylhex-4-en-1-ol
(5k). Yield¼76%
2.08e1.90 (m, 3H); 13C NMR (100 MHz, CDCl3):
d 147.96, 143.53,
(249 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C24H25
O
141.00,140.76,140.43,128.71 (2x),128.27 (2x),127.38,127.22,127.14
(2x), 127.00 (2x), 126.31 (2x), 126.08 (2x), 112.55, 73.71, 37.44, 31.50.
329.1905, found 329.1911; 1H NMR (400 MHz, CDCl3):
d 7.62e7.59
(m, 2H), 7.56 (d, J¼8.4 Hz, 2H), 7.46 (d, J¼8.4 Hz, 2H), 7.43e7.28 (m,
8H), 5.87 (t, J¼6.4 Hz,1H), 4.76 (dd, J¼5.6, 7.2 Hz,1H), 2.36e2.29 (m,
2H), 2.05 (s, 3H), 2.03e1.85 (m, 2H), 1.81 (br s, 1H); 13C NMR
4.3.6. 1-Naphthalen-2-yl-4-phenylpent-4-en-1-ol (6f). Yield¼78%
(225 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C21H21
O
(100 MHz, CDCl3):
d
144.58, 142.65, 140.83, 139.38, 134.91, 128.72
289.1592, found 289.1599; 1H NMR (400 MHz, CDCl3):
d 7.86e7.81 (m,
(2x),128.50 (2x),127.61 (2x),127.11, 126.93,126.86 (2x),125.94 (2x),
125.92 (2x), 74.18, 38.70, 29.68, 25.20, 15.74.
3H), 7.77 (br s, 1H), 7.51e7.48 (m, 2H), 7.46e7.38 (m, 3H), 7.35e7.27
(m, 3H), 5.33 (d, J¼0.8 Hz, 1H), 5.12 (d, J¼1.6 Hz, 1H), 4.89 (dd, J¼1.6,
7.6 Hz, 1H), 2.74e2.66 (m, 1H), 2.62e2.55 (m, 1H), 2.11e1.94 (m, 2H),
4.3. A representative synthetic procedure of skeleton 6 is as
follows
2.01 (br s, 1H); 13C NMR (100 MHz, CDCl3):
d 148.00, 141.84, 141.10,
133.24, 132.97, 128.28 (2x), 127.90, 127.65, 127.39, 126.10 (3x), 125.80
(2x), 124.60, 124.02, 112.58, 74.11, 37.37, 31.50.
Sodium amalgam (10%, 2.0 g) was added to a solution of skel-
eton 2 (1.0 mmol) in MeOH (10 mL) at rt. The reaction mixture was
stirred at rt for 2 h. The reaction mixture was filtrated and the
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3ꢁ20 mL). The
combined organic layers were washed with brine, dried, filtered
and evaporated to afford crude product under reduced pressure.
Purification on silica gel (hexanes/EtOAc¼8/1e4/1) afforded 6.
4.4. A representative synthetic procedure of skeletons 7 and 9
is as follows
Sodium amalgam (10%, 2.0 g) was added to a solution of skeleton
3 (1.0 mmol) in MeOH (10 mL) at rt. The reaction mixture was stirred
at rt for 2 h. The reaction mixture was filtrated and the solvent was
concentrated. The residue was diluted with water (10 mL) and the
mixture was extracted with CH2Cl2 (3ꢁ20 mL). The combined or-
ganic layers were washed with brine, dried, filtered and evaporated
to afford crude product under reduced pressure. Purification on
silica gel (hexanes/EtOAc¼8/1e4/1) afforded 7 and 9.
4.3.1. 1,4-Diphenylpent-4-en-1-ol (6a). Yield¼83% (198 mg); Col-
orless oil; HRMS (ESI, Mþþ1) calcd for C17H19O 239.1436, found
239.1441; 1H NMR (400 MHz, CDCl3):
d 7.42e7.27 (m, 10H), 5.33 (s,
1H), 5.12 (d, J¼1.6 Hz,1H), 4.72 (dd, J¼5.6,12.0 Hz,1H), 2.72e2.65 (m,
1H), 2.59e2.52 (m, 1H), 2.06 (br s, 1H), 2.04e1.84 (m, 2H); 13C NMR
4.4.1. 1-Phenylpent-4-en-1-ol (7a). Yield¼72% (117 mg); Colorless
oil; HRMS (ESI, Mþþ1) calcd for C11H15O 163.1123, found 163.1128;
(100 MHz, CDCl3): d 147.92, 144.47, 140.96, 128.40 (2x), 128.26 (2x),
127.52, 127.35, 126.05 (2x), 125.84 (2x), 112.51, 73.96, 37.42, 31.44.
1H NMR (400 MHz, CDCl3):
d 7.38e7.33 (m, 5H), 5.90e5.80 (m, 1H),
5.05 (dq, J¼1.6, 17.2 Hz, 1H), 4.99 (dq, J¼1.6, 10.0 Hz, 1H), 4.69 (dd,
4.3.2. 1-(4-Fluorophenyl)-4-phenylpent-4-en-1-ol (6b). Yield¼86%
(220 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C17H18FO
J¼5.2, 7.2 Hz, 1H), 2.22e2.09 (m, 2H), 2.07 (br s, 1H), 1.95e1.86 (m,
1H), 1.84e1.76 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 144.56, 138.14,
128.41, 127.51, 125.85 (3x), 114.90, 73.95, 37.98, 29.99.
257.1342, found 247.1344; 1H NMR (400 MHz, CDCl3):
d
7.39e7.24
(m, 7H), 7.05e6.99 (m, 2H), 5.31 (d, J¼1.2 Hz, 1H), 5.09 (d, J¼1.2 Hz,
1H), 4.69 (dd, J¼5.6, 7.6 Hz, 1H), 2.68e2.60 (m, 1H), 2.56e2.47 (m,
1H), 1.99 (br s, 1H), 1.98e1.89 (m, 1H), 1.87e1.79 (m, 1H); 13C NMR
4.4.2. 1-(4-Fluorophenyl)pent-4-en-1-ol (7b). Yield¼70% (126 mg);
Colorless oil; HRMS (ESI, Mþþ1) calcd for C11H14FO 181.1029, found
(100 MHz, CDCl3):
d
162.13 (d, J¼244.1 Hz), 147.84, 140.90, 140.21 (d,
181.1032; 1H NMR (400 MHz, CDCl3):
d 7.29e7.23 (m, 2H),
J¼3.0 Hz), 128.31 (2x), 127.50 (d, J¼8.4 Hz, 2x), 127.44, 126.06 (2x),
115.21 (d, J¼20.4 Hz, 2x), 112.64, 73.32, 37.54, 31.43.
7.03e6.97 (m, 2H), 5.85e5.75 (m, 1H), 5.03 (q, J¼1.6 Hz, 1H),
5.00e4.95 (m, 1H), 4.61 (dd, J¼6.0, 7.2 Hz, 1H), 2.55e2.54 (m, 1H),
2.13e2.01 (m, 2H), 1.87e1.79 (m, 1H), 1.76e1.67 (m, 1H); 13C NMR
4 . 3 . 3 . 1 - ( 4 - M e t h o x y p h e nyl ) - 4 - p h e nyl p e n t - 4 - e n - 1 - o l
(6c). Yield¼80% (214 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd
for C18H21O2 269.1542, found 269.1543; 1H NMR (400 MHz, CDCl3):
(100 MHz, CDCl3):
d
162.05 (d, J¼244.1 Hz), 140.24 (d, J¼3.0 Hz),
137.91, 127.45 (d, J¼7.6 Hz, 2x), 115.11 (d, J¼21.2 Hz, 2x), 114.96,
73.16, 38.00, 29.85.
d
7.40e7.29 (m, 5H), 7.25 (d, J¼8.4 Hz, 2H), 6.88 (d, J¼8.4 Hz, 2H),
5.30 (d, J¼0.8 Hz, 1H), 5.09 (d, J¼0.8 Hz, 1H), 4.66 (dd, J¼5.6, 7.6 Hz,
4.4.3. 1-(4-Methoxyphenyl)pent-4-en-1-ol (7c). Yield¼73% (140 mg);
Colorless oil; HRMS (ESI, Mþþ1) calcd for C12H17O2 193.1229, found
1H), 3.80 (s, 3H), 2.68e2.60 (m, 1H), 2.55e2.47 (m, 1H), 2.01e1.92
(m, 1H), 1.89e1.80 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
159.04,
193.1233; 1H NMR (400 MHz, CDCl3):
d
7.27 (d, J¼8.4 Hz, 2H), 6.88 (d,
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.07.043

6
C.-K. Chan et al. / Tetrahedron xxx (2016) 1e9
J¼8.4 Hz, 2H), 5.88e5.78 (m, 1H), 5.03 (dq, J¼2.0, 16.8 Hz, 1H), 4.97
(dq, J¼2.0, 10.0 Hz, 1H), 9.26 (dd, J¼6.4, 7.6 Hz, 1H), 3.80 (s, 3H),
2.17e2.04 (m, 2H), 1.94e1.85 (m, 2H), 1.81e1.72 (m, 1H); 13C NMR
CDCl3): d 7.16e7.00 (m, 8H), 5.80e5.68 (m, 2H), 4.88e4.87 (m, 2H),
4.85e4.82 (m, 2H), 2.36 (s, 6H), 2.34 (br s, 2H), 2.17e2.09 (m, 2H),
1.95e1.87 (m, 2H), 1.75e1.61 (m, 4H).
(100 MHz, CDCl3): d 159.01, 138.20, 136.73, 127.11 (2x), 114.82, 113.80
(2x), 73.56, 55.22, 37.91, 30.07.
4.5. A representative synthetic procedure of skeleton 8 is as
follows
4.4.4. 1-p-Tolylpent-4-en-1-ol (7d). Yield¼75% (132 mg); Colorless
oil; HRMS (ESI, Mþþ1) calcd for C12H17O 177.1280, found 177.1285;
Sodium amalgam (10%, 2.0 g) was added to a solution of skel-
eton 4 (1.0 mmol) in MeOH (10 mL) at rt. The reaction mixture was
stirred at rt for 2 h. The reaction mixture was filtrated and the
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3ꢁ20 mL). The
combined organic layers were washed with brine, dried, filtered
and evaporated to afford crude product under reduced pressure.
Purification on silica gel (hexanes/EtOAc¼8/1e4/1) afforded 8.
1H NMR (400 MHz, CDCl3):
d
7.24 (d, J¼8.0 Hz, 2H), 7.17 (d, J¼8.0 Hz,
2H), 5.90e5.80 (m, 1H), 5.05 (dq, J¼2.0, 17.2 Hz, 1H), 4.99 (dq, J¼2.0,
11.8 Hz, 1H), 4.65 (dd, J¼5.6, 7.6 Hz, 1H), 2.36 (s, 3H), 2.20e2.04 (m,
2H), 2.00 (br s, 1H), 1.94e1.74 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
141.60, 138.20, 129.09 (4x), 125.81, 114.83, 73.79, 37.92, 30.05,
21.06.
4.4.5. 1-Biphenyl-4-yl-pent4-en-1-ol (7e). Yield¼78% (186 mg);
Colorless solid; mp¼60e61 ꢀC (recrystallized from hexanes and
EtOAc); HRMS (ESI, Mþþ1) calcd for C17H19O 239.1436, found
4.5.1. 5-Methyl-1-phenylhex-4-en-1-ol (8a). Yield¼86% (163 mg);
Colorless oil; HRMS (ESI, Mþþ1) calcd for C13H19O 191.1436, found
239.1437; 1H NMR (400 MHz, CDCl3):
d
7.63e7.59 (m, 4H),
191.1439; 1H NMR (400 MHz, CDCl3):
d 7.38e7.26 (m, 5H), 5.18e5.13
7.49e7.36 (m, 5H), 5.94e5.84 (m, 1H), 5.10 (dq, J¼1.6, 10.0 Hz, 1H),
(m, 1H), 4.67 (dd, J¼6.0, 8.0 Hz, 1H), 2.10 (br s, 1H), 2.10e2.03 (m,
5.04 (dq, J¼1.6, 17.2 Hz, 1H), 4.75 (dd, J¼5.6, 7.6 Hz, 1H), 2.26e2.12
2H), 1.89e1.71 (m, 2H), 1.71 (d, J¼0.8 Hz, 3H), 1.60 (s, 3H); 13C NMR
(m, 3H), 2.01e1.82 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
143.58,
(100 MHz, CDCl3): d 144.72, 132.23, 128.35 (2x), 127.40, 125.86 (2x),
140.74, 140.39, 138.11, 128.71 (2x), 127.21, 127.12 (4x), 126.30 (2x),
114.96, 73.65, 37.95, 30.01.
123.76, 74.17, 38.96, 25.68, 24.42, 17.67.
4.5.2. 1-(4-Fluorophenyl)-5-methylhex-4-en-1-ol (8b). Yield¼85%
(177 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C13H18FO
4.4.6. 1-Naphthalen-2-yl-pent-4-en-1-ol (7f). Yield¼74% (157 mg);
Colorless oil; HRMS (ESI, Mþþ1) calcd for C15H17O 213.1280, found
209.1342, found 209.1348; 1H NMR (400 MHz, CDCl3):
d 7.33e7.27
213.1284; 1H NMR (400 MHz, CDCl3):
d
7.87e7.83 (m, 3H), 7.77 (s,
(m, 2H), 7.04e6.98 (m, 2H), 5.15e5.10 (m, 1H), 4.64 (dd, J¼6.0,
1H), 7.53e7.46 (m, 3H), 5.92e5.82 (m, 1H), 5.07 (dq, J¼1.6, 17.2 Hz,
1H), 5.02 (dq, J¼1.6, 10.4 Hz, 1H), 4.84 (dd, J¼6.0, 7.2 Hz, 1H), 2.36
(br s,1H), 2.23e2.11 (m, 2H), 2.03e1.87 (m, 2H); 13C NMR (100 MHz,
7.6 Hz, 1H), 2.15 (br s, 1H), 2.10e1.98 (m, 2H),1.85e1.76 (m, 2H), 1.69
(s, 3H), 1.58 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 162.06 (d,
J¼243.3 Hz), 140.43 (d, J¼3.0 Hz), 132.39, 127.49 (d, J¼8.3 Hz, 2x),
CDCl3):
d 141.87, 138.09, 133.19, 132.92, 128.22, 127.86, 127.61,
123.59, 115.12 (d, J¼20.5 Hz, 2x), 73.53, 39.04, 25.67, 24.35, 17.65.
126.06, 125.74, 124.56, 124.00, 114.93, 74.01, 37.83, 29.97.
4.5.3. 5-Methyl-1-p-tolylhex-4-en-1-ol (8c). Yield¼84% (171 mg);
Colorless oil; HRMS (ESI, Mþþ1) calcd for C14H21O 205.1592, found
4.4.7. 5,6-Diphenyldeca-1,9-diene-5,6-diol
(9a). Two
isomers
(ratio¼1:1). Yield¼12% (39 mg); Colorless oil; HRMS (ESI, Mþþ1)
205.1593; 1H NMR (400 MHz, CDCl3):
d
7.23 (d, J¼8.0 Hz, 2H), 7.16
calcd for C22H27O2 323.2011, found 323.2013; 1H NMR (400 MHz,
(d, J¼8.0 Hz, 2H), 5.18e5.13 (m, 1H), 4.63 (dd, J¼6.0, 7.6 Hz,1H), 2.36
CDCl3):
d 7.30e7.25 (m, 8H), 7.18 (br s, 2H), 5.82e5.72 (m, 2H),
(s, 3H), 2.14 (br s, 1H), 2.11e2.02 (m, 2H), 1.88e1.79 (m, 2H), 1.71 (s,
4.90e4.85 (m, 4H), 2.47e2.27 (m, 2H), 2.45e2.15 (m, 2H),
2.00e1.89 (m, 2H), 1.80e1.64 (m, 4H).
3H), 1.60 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 141.75, 136.99,
132.10, 129.01 (2x), 125.83 (2x), 123.84, 73.98, 38.87, 25.67, 24.45,
21.04, 17.67.
4.4.8. 5,6-Bis-(4-fluorophenyl)deca-1,9-diene-5,6-diol
(9b). Two
isomers (ratio¼1:1). Yield¼8% (29 mg); Colorless oil; HRMS (ESI,
4.5.4. 5,9-Dimethyl-1-phenyldeca-4,8-dien-1-ol
(8d). Yield¼85%
Mþþ1) calcd for C22H25F2O2 359.1823, found 359.1826; 1H NMR
(219 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C18H27
O
(400 MHz, CDCl3):
d
7.16 (br s, 2H), 7.07 (br s, 2H), 6.97e6.92 (m,
259.2062, found 259.2066; 1H NMR (400 MHz, CDCl3):
d 7.37e7.27
4H), 5.76e5.71 (m, 2H), 4.90e4.83 (m, 4H), 2.38e2.28 (m, 2H),
2.22e2.14 (m, 2H), 1.85e1.84 (m, 2H), 1.75e1.62 (m, 4H).
(m, 5H), 5.19e5.11 (m, 2H), 4.66 (dd, J¼6.0, 7.6 Hz, 1H), 2.25 (br s,
1H), 2.17e2.00 (m, 4H), 1.90e1.74 (m, 4H), 1.71 (s, 3H), 1.63 (s, 3H),
1.60 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 144.74, 135.76, 131.29,
4.4.9. 5,6-Bis-(4-methoxyphenyl)deca-1,9-diene-5,6-diol (9c). Two
isomers (ratio¼1:1). Yield¼10% (38 mg); Colorless solid;
mp¼104e105 ꢀC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C24H31O4 383.2222, found 383.2229; 1H NMR
128.28 (2x), 127.32, 125.83 (2x), 124.23, 123.66, 74.07, 39.63, 38.94,
26.58, 25.62, 24.26, 17.61, 15.93.
4.5.5. 5,9,13-Trimethyl-1-phenyltetradeca-4,8,12-trien-1-ol
(8e). Yield¼86% (280 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd
for C23H35O 327.2688, found 327.2692; 1H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3):
d 7.11 (br s, 2H), 7.05 (br s, 2H), 6.81e6.78 (m,
4H), 5.80e5.70 (m, 2H), 4.88e4.83 (m, 4H), 3.82 (s, 3H), 3.80 (s, 3H),
2.36e2.30 (m, 2H), 2.17e2.11 (m, 2H), 1.95e1.87 (m, 2H), 1.72e1.62
(m, 4H). Single-crystal X-ray diagram: crystal of compound 9c was
grown by slow diffusion of EtOAc into a solution of compound 9c in
CH2Cl2 to yield colorless prisms. The compound crystallizes in the
d
7.38e7.34 (m, 3H), 7.31e7.27 (m, 2H), 5.20e5.11 (m, 2H), 4.66 (dd,
J¼5.6, 7.2 Hz, 1H), 2.21 (br s, 1H), 2.14e1.98 (m, 9H), 1.90e1.73 (m,
4H), 1.71 (s, 3H), 1.64 (s, 3H), 1.62 (s, 3H), 1.61 (s, 3H); 13C NMR
(100 MHz, CDCl3):
d 144.75, 135.76, 134.92, 131.14, 128.29 (2x),
ꢀ
orthorhombic crystal system, space group F d d 2, a¼30.158(6) A,
127.32, 125.84 (2x), 124.33, 124.09, 123.67, 74.10, 39.65 (2x), 38.96,
26.69, 26.52, 25.61, 24.28, 17.59, 15.96, 15.93.
3
ꢀ
ꢀ
ꢀ
b¼8.6837(18) A, c¼15.926(3) A, V¼4170.8(15) A , Z¼8,
dcalcd¼1.225 g/cm3, F(000)¼1664, 2
q
range 2.893e26.470ꢀ, R in-
dices (all data) R1¼0.0400, wR2¼0.1073.
4.6. A representative synthetic procedure of skeleton 11 is as
follows
4.4.10. 5,6-Di-p-tolyldeca-1,9-diene-5,6-diol (9d). Two isomers
(ratio¼1:1). Yield¼8% (28 mg); Colorless oil; HRMS (ESI, Mþþ1)
calcd for C24H31O2 351.2324, found 351.2328; 1H NMR (400 MHz,
Sodium amalgam (10%, 2.0 g) was added to a solution of skel-
eton 10 (1.0 mmol) in MeOH (10 mL) at rt. The reaction mixture was
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.07.043

C.-K. Chan et al. / Tetrahedron xxx (2016) 1e9
7
stirred at rt for 2 h. The reaction mixture was filtrated and the
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3ꢁ20 mL). The
combined organic layers were washed with brine, dried, filtered
and evaporated to afford crude product under reduced pressure.
Purification on silica gel (hexanes/EtOAc¼8/1e4/1) afforded 11.
(d, J¼5.3 Hz), 128.50 (d, J¼15.9 Hz), 128.24 (2x), 127.41, 127.34 (2x),
125.28 (d, J¼3.8 Hz), 114.99 (d, J¼22.0 Hz), 73.57, 38.84, 25.29,
25.26.
4.7.3. 3-(3-Methoxyphenyl)-1-phenylpropan-1-ol (13c). Yield¼73%
(177 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C16H19O2
243.1385, found 243.1382; 1H NMR (400 MHz, CDCl3):
d 7.43 (s, 1H),
4.6.1. 1-Phenylpent-4-yn-1-ol (11a). Yield¼76% (122 mg); Colorless
oil; HRMS (ESI, Mþþ1) calcd for C11H13O 161.0966, found 161.0968;
7.42 (br s, 2H), 7.40e7.34 (m, 1H), 7.33e7.29 (m, 2H), 6.91e6.84 (m,
3H), 4.72 (dd, J¼5.6, 7.6 Hz, 1H), 3.82 (s, 3H), 3.29 (br s, 1H),
2.86e2.69 (m, 2H), 2.30e2.07 (m, 2H); 13C NMR (100 MHz, CDCl3):
1H NMR (400 MHz, CDCl3):
d 7.36 (br s, 1H), 7.35 (br s, 3H),
7.32e7.27 (m, 1H), 4.82 (dd, J¼5.2, 8.0 Hz, 1H), 2.38e2.30 (m, 2H),
d 159.28, 144.38, 143.24, 129.01, 128.08 (2x), 127.11, 125.70 (2x),
120.60, 113.94, 110.86, 73.26, 54.68, 40.05, 31.75.
2.27e2.18 (m, 1H), 2.03e1.84 (m, 3H); 13C NMR (100 MHz, CDCl3):
d
143.96, 128.45 (2x), 127.63, 125.76 (2x), 83.85, 72.98, 68.91, 37.32,
15.03.
4.7.4. 3-Naphthalen-1-yl-1-phenylpropan-1-ol
(13d). Yield¼70%
(183 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C19H19
O
4.6.2. 1-p-Tolylpent-4-yn-1-ol (11b). Yield¼70% (122 mg); Color-
less oil; HRMS (ESI, Mþþ1) calcd for C12H15O 175.1123, found
263.1436, found 263.1437; 1H NMR (400 MHz, CDCl3):
d 8.17e8.15
(m, 1H), 8.04e8.00 (m, 1H), 7.88 (d, J¼8.4 Hz, 1H), 7.67e7.61 (m,
2H), 7.57e7.41 (m, 7H), 4.85 (dd, J¼5.6, 7.6 Hz, 1H), 3.42e3.34 (m,
1H), 3.27e3.19 (m, 1H), 3.08 (s, 1H), 2.43e2.24 (m, 2H); 13C NMR
175.1126; 1H NMR (400 MHz, CDCl3):
d
7.24 (d, J¼8.4 Hz, 2H), 7.17
(d, J¼8.4 Hz, 2H), 4.79 (dd, J¼5.2, 8.0 Hz,1H), 2.36 (s, 3H), 2.35e2.29
(m, 1H), 2.26e2.18 (m, 2H), 2.00 (t, J¼2.8 Hz, 1H), 2.03e1.83 (m,
(100 MHz, CDCl3):
d 144.36, 137.88, 133.72, 131.69, 128.56, 128.22
2H); 13C NMR (100 MHz, CDCl3):
d
140.99, 137.30, 129.12 (2x),
(2x), 127.31, 126.45, 125.80 (2x), 125.72, 125.59, 125.36, 125.25,
123.63, 73.76, 39.58, 28.83.
125.72 (2x), 83.93, 72.85, 68.81, 37.29, 21.03, 15.06.
4.6.3. 1-Phenylhex-4-yn-1-ol (11c). Yield¼74% (129 mg); Colorless
oil; HRMS (ESI, Mþþ1) calcd for C12H15O 175.1123, found 175.1127;
4.7.5. 1-(4-Fluorophenyl)-3-phenylpropan-1-ol
(13e). Yield¼72%
(166 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C15H16FO
1H NMR (400 MHz, CDCl3):
d
7.33e7.28 (m, 3H), 7.25e7.21 (m, 2H),
231.1185, found 231.1191; 1H NMR (400 MHz, CDCl3):
d 7.34e7.27
4.78 (dd, J¼4.8, 8.0 Hz, 1H), 2.29e2.10 (m, 3H), 1.94e1.77 (m, 2H),
(m, 4H), 7.22e7.18 (m, 3H), 7.07e7.01 (m, 2H), 4.67 (dd, J¼5.2,
8.0 Hz,1H), 2.78e2.62 (m, 2H), 2.17e1.97 (m, 2H),1.96 (br s,1H); 13
NMR (100 MHz, CDCl3):
J¼3.0 Hz), 128.40 (4x), 127.53 (d, J¼7.6 Hz, 2x), 125.91, 115.27 (d,
J¼21.3 Hz, 2x), 73.16, 40.52, 31.97.
1.76 (t, J¼2.4 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
144.21, 128.40
C
(2x), 127.50, 125.78 (2x), 78.44, 76.39, 73.40, 37.89, 15.39, 3.42.
d
162.18 (d, J¼244.1 Hz), 141.55, 140.27 (d,
4.6.4. 1-Phenylhept-4-yn-1-ol (11d). Yield¼73% (137 mg); Colorless
oil; HRMS (ESI, Mþþ1) calcd for C13H17O 189.1280, found 189.1287;
1H NMR (400 MHz, CDCl3):
d
7.37e7.25 (m, 5H), 4.84 (dd, J¼5.2,
4.7.6. 1-Phenylhexan-1-ol (13f). Yield¼77% (137 mg); Colorless oil;
HRMS (ESI, Mþþ1) calcd for C12H19O 179.1436, found 179.1438; 1H
8.4 Hz, 1H), 2.35e2.15 (m, 5H), 1.99e1.82 (m, 2H), 1.14 (t, J¼7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3):
d
144.20, 128.40 (2x), 127.50,
NMR (400 MHz, CDCl3):
d
7.37e7.25 (m, 5H), 4.63 (dd, J¼6.0, 7.2 Hz,
125.77 (2x), 82.69, 78.63, 73.47, 37.97, 15.44, 14.26, 12.38.
1H), 2.25 (br s, 1H), 1.84e1.65 (m, 2H), 1.46e1.38 (m, 1H), 1.37e1.23
(m, 5H), 0.91e0.88 (m, 3H); 13C NMR (100 MHz, CDCl3):
d
144.91,
128.31 (2x), 127.34, 125.85 (2x), 74.57, 38.98, 31.67, 25.43, 22.50,
13.95.
4.7. A representative synthetic procedure of skeleton 13 is as
follows
Sodium amalgam (10%, 2.0 g) was added to a solution of skel-
eton 12 (1.0 mmol) in MeOH (10 mL) at rt. The reaction mixture
was stirred at rt for 2 h. The reaction mixture was filtrated and the
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3ꢁ20 mL).
The combined organic layers were washed with brine, dried, fil-
tered and evaporated to afford crude product under reduced
pressure. Purification on silica gel (hexanes/EtOAc¼8/1e4/1)
afforded 13.
4.8. A representative synthetic procedure of skeleton 15 is as
follows
Sodium amalgam (10%, 2.0 g) was added to a solution of skel-
eton 14 (1.0 mmol) in MeOH (10 mL) at rt. The reaction mixture
was stirred at rt for 2 h. The reaction mixture was filtrated and the
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3ꢁ20 mL).
The combined organic layers were washed with brine, dried, fil-
tered and evaporated to afford crude product under reduced
pressure. Purification on silica gel (hexanes/EtOAc¼8/1e4/1)
afforded 15.
4.7.1. 1,3-Diphenylpropan-1-ol (13a). Yield¼76% (161 mg); Color-
less oil; HRMS (ESI, Mþþ1) calcd for C15H17O 213.1280, found
213.1287; 1H NMR (400 MHz, CDCl3):
d 7.44e7.34 (m, 7H),
7.29e7.25 (m, 3H), 4.70 (dd, J¼5.6, 8.0 Hz, 1H), 2.84e2.68 (m, 2H),
4.8.1. Cyclohexanol (15a). Yield¼78% (78 mg); Colorless oil; 1H
2.53 (s, 1H), 2.23e2.04 (m, 2H); 13C NMR (100 MHz, CDCl3):
NMR (200 MHz, CDCl3):
d 3.66e3.64 (m, 1H), 1.92e1.89 (m, 2H),
d
144.46, 141.70, 128.34 (4x), 128.25 (2x), 127.43, 125.84 (2x), 125.71,
1.76e1.74 (m, 2H), 1.62e1.58 (m, 2H), 1.32e1.27 (m, 5H).
73.63, 40.30, 31.89.
4.8.2. Cycloheptanol (15b). Yield¼70% (80 mg); Colorless oil; 1H
4.7.2. 3-(2-Fluorophenyl)-1-phenylpropan-1-ol
(13b). Yield¼78%
NMR (200 MHz, CDCl3): d 3.82e3.79 (m, 1H), 2.10e1.61 (m, 13H).
(179 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C15H16FO
231.1185, found 231.1186; 1H NMR (400 MHz, CDCl3):
d
7.43e7.32
4.8.3. 1-(4-Methoxyphenyl)-3-phenylpropan-1-ol (15c). Yield¼70%
(m, 5H), 7.29e7.21 (m, 2H), 7.15e7.06 (m, 2H), 4.70 (dd, J¼5.6,
(104 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for C10H13
O
8.0 Hz, 1H), 3.03 (br s, 1H), 2.91e2.72 (m, 2H), 2.21e2.04 (m, 2H);
149.0966, found 149.0968; 1H NMR (400 MHz, CDCl3):
d 7.45e7.41
13C NMR (100 MHz, CDCl3):
d
161.01 (d, J¼242.6 Hz), 144.27, 130.46
(m, 1H), 7.23e7.19 (m, 2H), 7.13e7.10 (m, 1H), 4.76 (t, J¼4.8 Hz, 1H),
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.07.043

8
C.-K. Chan et al. / Tetrahedron xxx (2016) 1e9
2.87e2.80 (m, 1H), 2.77e2.70 (m, 1H), 2.18 (br s, 1H), 2.03e1.87 (m,
3H), 1.82e1.74 (m, 1H); 13C NMR (100 MHz, CDCl3):
138.74, 136.98,
128.85, 128.56, 127.40, 126.02, 67.96, 32.14, 29.14, 18.74.
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3ꢁ20 mL). The
combined organic layers were washed with brine, dried, filtered
and evaporated to afford crude product under reduced pressure.
Purification on silica gel (hexanes/EtOAc¼8/1e6/1) afforded 18.
d
4.8.4. 3,4,30,40-Tetrahydro-2H,20H-[1,10]binaphthalenyl-1,10-diol (15c-
1). Yield¼8% (24 mg); Colorless solid; mp¼127e129 ꢀC (recrys-
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
4.9.1. 1-Phenylethanol (18a). Yield¼80% (98 mg); Colorless oil; 1H
C
20H23O2 295.1698, found 295.1699; 1H NMR (400 MHz, CDCl3):
NMR (200 MHz, CDCl3):
2.10 (br s, 1H), 1.40 (d, J¼6.8 Hz, 3H).
d
7.30e7.22 (m, 5H), 4.75 (q, J¼6.8 Hz, 1H),
d
8.22e8.19 (m, 2H), 7.27e7.19 (m, 4H), 7.11 (br d, J¼7.6 Hz, 2H), 2.80
(br s, 2H), 2.75e2.69 (m, 2H), 2.60e2.52 (m, 2H), 1.71e1.59 (m, 6H),
1.32e1.24 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
140.52 (2x), 138.36
4.9.2. 1-(4-Fluorophenyl)ethanol (18b). Yield¼71% (99 mg); Color-
(2x), 129.02 (2x), 128.84 (2x), 127.18 (2x), 126.36 (2x), 77.14 (2x),
36.41 (2x), 31.12 (2x), 20.05 (2x). Single-crystal X-ray diagram:
crystal of compound 14a was grown by slow diffusion of EtOAc into
a solution of compound 14a in CH2Cl2 to yield colorless prisms. The
compound crystallizes in the triclinic crystal system, space group
less oil; 1H NMR (200 MHz, CDCl3):
d 7.20e7.16 (m, 2H), 6.94e6.90
(m, 2H), 4.89 (q, J¼6.8 Hz, 1H), 2.04 (br s, 1H), 1.46 (d, J¼6.8 Hz, 3H).
4.9.3. 1-(4-Methoxyphenyl)ethanol (18c). Yield¼73% (111 mg);
Colorless oil; 1H NMR (200 MHz, CDCl3):
6.88 (d, J¼8.4 Hz, 2H), 4.86 (q, J¼6.8 Hz, 1H), 3.81 (s, 3H), 1.93 (br s,
1H), 1.47 (d, J¼6.8 Hz, 3H).
d
7.30 (d, J¼8.4 Hz, 2H),
ꢀ
ꢀ
ꢀ
Pd1, a¼8.4772(8) A, b¼8.4990(8) A, c¼11.5994(11) A,
V¼743.96(12) A , Z¼2, dcalcd¼1.314 g/cm3, F(000)¼316, 2
q
range
3
ꢀ
1.958e26.402ꢀ, R indices (all data) R1¼0.0444, wR2¼0.0935.
Acknowledgements
4 . 8 . 5 . 6 , 7 , 8 , 9 -Te t ra hy d ro - 5 H - b e n z o c yc l o h e p t e n - 5 - o l
(15d). Yield¼76% (123 mg); Colorless solid; mp¼100e102 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C11H15O 163.1123, found 163.1128; 1H NMR (400 MHz, CDCl3):
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).
d
7.45 (d, J¼7.2 Hz, 1H), 7.24e7.10 (m, 3H), 4.92 (d, J¼8.8 Hz, 1H),
2.95 (d, J¼8.4 Hz, 1H), 2.92 (d, J¼8.4 Hz, 1H), 2.18 (br s, 1H),
2.10e2.01 (m, 1H), 1.99e1.91 (m, 1H), 1.86e1.75 (m, 3H), 1.52e1.44
Supplementary data
(m, 1H); 13C NMR (100 MHz, CDCl3):
d 144.22, 140.70, 129.39,
Supplementary data (Experimental procedure and scanned
photocopies of NMR (CDCl3) spectral data were supported) asso-
ciated with this article can be found in the online version, at http://
dx.doi.org/10.1016/j.tet.2016.07.043.
126.86, 126.01, 124.54, 73.85, 36.51, 35.66, 27.73, 27.54.
4.8.6. 4-(3,4-Dichloro-phenyl)-1,2,3,4-tetrahydro-naphthalen-1-ol
(15e). Yield¼76% (222 mg); Colorless gum; HRMS (ESI, Mþþ1)
calcd for C16H15Cl2O 293.0500, found 293.0506; 1H NMR (400 MHz,
References and notes
CDCl3):
d
7.46 (d, J¼7.6 Hz, 1H), 7.36 (d, J¼8.4 Hz, 1H), 7.28e7.24 (m,
1. For reviews and books of sulfone chemistry, see (a) El-Awa, A.; Noshi, M. N.;
Mollat du Jourdin, X.; Fuchs, P. L. Chem. Rev. 2009, 109, 2315; (b) Trost, B. M. Bull.
Chem. Soc. Jpn. 1988, 61, 107; (c) Simpkins, N. S. Sulphones in Organic Synthesis;
Pergamon: Oxford, UK, 1993; (d) The Chemistry of Sulphones and Sulphoxides;
Patai, S., Rappoport, Z., Stirling, C., Eds.; Wiley: Chichester, UK, 1988; (e) Najera,
C.; Yus, M. Tetrahedron 1999, 55, 10546.
2H), 7.20e7.15 (m, 1H), 6.99 (dd, J¼2.0, 8.4 Hz,1H), 6.83 (d, J¼7.6 Hz,
1H), 4.86 (t, J¼4.0 Hz, 1H), 4.00 (dd, J¼6.0, 8.4 Hz,1H), 2.13e1.95 (m,
5H); 13C NMR (100 MHz, CDCl3):
d 146.95, 138.89, 138.38, 132.35,
130.68, 130.32, 130.21, 129.71, 129.03, 128.23, 128.12, 127.03, 67.82,
45.04, 30.04, 28.12.
2. Recent preparations of functionalized b-ketosulfones, see (a) Zhou, G.; Ting, P.
T.; Aslanian, R. G. Tetrahedron Lett. 2010, 51, 939; (b) Pospisil, J.; Sato, H. J. Org.
Chem. 2011, 76, 2269; (c) Tsui, G. C.; Glenadel, Q.; Lau, C.; Lautens, M. Org. Lett.
2011, 13, 208; (d) Kumar, A.; Muthyala, M. K. Tetrahedron Lett. 2011, 52, 5368; (e)
Sreedhar, B.; Rawat, V. S. Synlett 2012, 413; (f) Lu, Q.; Zhang, J.; Zhao, G.; Qi, Y.;
Wang, H.; Lei, W. J. Am. Chem. Soc. 2013, 135, 11481; (g) Singh, A. K.; Chawla, A.
K.; Chawla, R.; Keshari, T.; Yadav, V. K.; Yadav, L. D. S. Org. Biomol. Chem. 2014,
12, 8550; (h) Chawla, R.; Singh, A. K.; Yadav, L. D. S. Eur. J. Org. Chem. 2014, 10,
2032; (i) Singh, A. K.; Chawla, R.; Yadav, L. D. S. Tetrahedron Lett. 2014, 55, 4742;
(j) Shi, X.; Ren, X.; Ren, Z.; Li, J.; Wang, Y.; Yang, S.; Gu, J.; Gao, Q.; Huang, G. Eur.
J. Org. Chem. 2014, 10, 5083; (k) Handa, S.; Fennewald, J. C.; Lipshutz, B. H.
Angew. Chem., Int. Ed. 2014, 53, 3432; (l) Tang, X.; Huang, L.; Xu, Y.; Yang, J.; Wu,
W.; Jiang, H. Angew. Chem., Int. Ed. 2014, 53, 4205; (m) Chang, M.-Y.; Cheng, Y.-C.
Org. Lett. 2015, 17, 5702; (n) Yadav, V. K.; Srivastava, V. P.; Yadav, L. D. Synlett
2016, 427.
4.8.7. 4-(3,4-Dichloro-phenyl)-3,4-dihydro-2H-naphthalen-1-one
(16). PCC (430 mg, 2.0 mmol) and Celite (2.0 g) were added to
a solution of 15e (290 mg, 1.0 mmol) in CH2Cl2 (20 mL) at rt. The
reaction mixture was stirred at rt for 8 h. The reaction mixture was
filtrated and the solvent was concentrated. The residue was diluted
with water (10 mL) and the mixture was extracted with CH2Cl2
(3ꢁ20 mL). The combined organic layers were washed with brine,
dried, filtered and evaporated to afford crude product under re-
duced pressure. Purification on silica gel (hexanes/EtOAc¼8/1)
afforded
16.
Yield¼80%
(232
mg);
Colorless
solid;
mp¼100e102 ꢀC(recrystallized from hexanes and EtOAc); HRMS
3. Recent synthetic applications on
b-ketosulfones, for 1,4-diketones (a) Xuan, J.;
Feng, Z.-J.; Chen, J. R.; Lu, L.-Q.; Xiao, W.-J. Chem.dEur. J. 2014, 20, 3045 For
a
-
(ESI, Mþþ1) calcd for C16H13Cl2O 291.0344, found 291.0349; 1H
methenyl ketones, see; (b) Pandey, G.; Vaitla, J. Org. Lett. 2015, 17, 4890; (c)
Kuninobu, Y.; Matsuzaki, H.; Nishi, M.; Takai, K. Org. Lett. 2011, 13, 2959 For
cyclic sulfones, see; (d) Wang, Q.-G.; Zhou, Q.-Q.; Deng, J.-G.; Chen, Y.-C. Org.
Lett. 2013, 15, 4786 For 1,2,3-triazoles, see; (e) Saraiva, M. T.; Costa, G. P.; Seus,
N.; Schumacher, R. F.; Perin, G.; Paixao, M. W.; Luque, R.; Alves, D. Org. Lett.
2015, 17, 6206 For pyrazoles, see; (f) Kumar, R.; Namboothiri, I. N. N. Org. Lett.
2011, 13, 4016; (g) Kumar, R.; Nair, D.; Namboothiri, I. N. N. Tetrahedron 2014, 70,
1794 For dihydrofurans, see; (h) Bouhlel, A.; Curti, C.; Tabele, C.; Vanelle, P.
Molecules 2013, 18, 4293.
NMR (400 MHz, CDCl3):
d
8.10 (dd, J¼1.6, 8.0 Hz, 1H), 7.45 (dt, J¼1.6,
8.0 Hz, 1H), 7.38 (d, J¼8.0 Hz, 2H), 7.21 (d, J¼2.0 Hz, 1H), 6.95 (d,
J¼2.0 Hz, 1H), 6.93 (d, J¼2.0 Hz, 1H), 4.26 (dd, J¼4.4, 8.0 Hz, 1H),
2.74e2.58 (m, 2H), 2.49e2.41 (m, 1H), 2.29e2.20 (m, 1H); 13C NMR
(100 MHz, CDCl3):
d 197.32, 144.80, 143.94, 133.79, 132.66, 132.57,
130.84, 130.52, 130.43, 129.20, 127.89, 127.43, 127.27, 44.41, 36.44,
31.56.
4. Synthetic applications on b-ketosulfones by authors, for styrylsulfones, see (a)
Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K. Synlett 2014, 1739 For vinylcyclopropanes,
see; (b) Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K. Tetrahedron 2014, 70, 8908 For
tetrahydrofurans, see; (c) Chang, M.-Y.; Cheng, Y.-C. Synlett 2016, 854 For tet-
rahydropyrans, see; (d) Chang, M.-Y.; Lu, Y.-J.; Cheng, Y.-C. Tetrahedron 2015, 71,
1192 dihydropyrans, see; (e) Chang, M.-Y.; Chen, Y.-H.; Cheng, Y.-C. Tetrahedron
2016, 72, 518 For pyrroles, see; (f) Chang, M.-Y.; Cheng, Y.-C.; Lu, Y.-J. Org. Lett.
2014, 16, 6252 For vinylfurans, see; (g) Chan, C.-K.; Lu, Y.-J.; Chang, M.-Y. Tet-
rahedron 2015, 71, 9544 For arylfurans, see; (h) Chang, M.-Y.; Cheng, Y.-C.; Lu,
Y.-J. Org. Lett. 2015, 17, 1264 For arenes, see; (i) Chang, M.-Y.; Cheng, Y.-C.; Lu, Y.-
4.9. A representative synthetic procedure of skeleton 18 is as
follows
Sodium amalgam (10%, 2.0 g) was added to a solution of skel-
eton 17 (1.0 mmol) in MeOH (10 mL) at rt. The reaction mixture was
stirred at rt for 2 h. The reaction mixture was filtrated and the
Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.07.043

C.-K. Chan et al. / Tetrahedron xxx (2016) 1e9
9
J. Org. Lett. 2015, 17, 3142 For arylpyridazines, see; (j) Chang, M.-Y.; Lu, Y.-J.;
Cheng, Y.-C. Tetrahedron 2015, 71, 6840 For benzosuberans, see; (k) Chang, M.-
Y.; Cheng, Y.-C. Org. Lett. 2016, 18, 608 For aryltetralins, see; (l) Chang, M.-Y.;
Cheng, Y.-C. Org. Lett. 2016, 18, 1682 For arylnaphthalenes, see; (m) Chang, M.-
Y.; Huang, Y.-H.; Wang, H.-S. Tetrahedron 2016, 72, 1888 For phenanthrenes,
see; (n) Chang, M.-Y.; Chen, Y.-C.; Chan, C.-K. Tetrahedron 2015, 71, 782 For
phenanthrofurans, see; (o) Chan, C.-K.; Chen, Y.-C.; Chen, Y.-L.; Chang, M.-Y.
Tetrahedron 2015, 71, 9187.
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Please cite this article in press as: Chan, C.-K.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.07.043