2-Aryl-3,4-dihydropyrans as building blocks for organic synthesis: Ring-opening reactions with nucleophiles

Article abstract of DOI:10.1016/j.tet.2011.08.075

An electrophilic ring-opening reaction of 2-aryl-3,4-dihydropyran with many nucleophiles, such as thiophenols, thiols, benzenesulfinic acid, resorcin, 2-methylfuran, benzamide and allyltrimethylsilane, was developed. In the presence of an appropriate cata

Full text of DOI:10.1016/j.tet.2011.08.075

Tetrahedron 67 (2011) 8314e8320
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2-Aryl-3,4-dihydropyrans as building blocks for organic synthesis: ring-opening
reactions with nucleophiles
,b,
Minghao Li a, Yanlong Gu a
*
a Institute of Physical Chemistry and Industrial Catalysis, Hubei Key Laboratory of Material Chemistry and Service Failure, School of Chemistry and Chemical Engineering, Huazhong
University of Science and Technology, 1037 Luoyu Road, Hongshan District, Wuhan 430074, China
b State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Lanzhou 730000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 July 2011
Received in revised form 19 August 2011
Accepted 26 August 2011
Available online 30 August 2011
An electrophilic ring-opening reaction of 2-aryl-3,4-dihydropyran with many nucleophiles, such as
thiophenols, thiols, benzenesulfinic acid, resorcin, 2-methylfuran, benzamide and allyltrimethylsilane,
was developed. In the presence of an appropriate catalyst, a product that contains not only a moiety of
the nucleophile but also a fragment of 1,3-dicarbonyl compound was obtained.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Ring-opening reaction
2-Aryl-3,4-dihydropyran
Acid catalysis
1,3-Dicarbonyl compound
Manganese(II) bromide
1. Introduction
we have developed a novel ring-opening reaction of 2-substituted
3,4-dihydropyrans with nucleophiles.6 However, for the reactions
Heterocyclic compounds display an intrinsic reactivity, which
enables rich, versatile and productive transformations. Taking into
account their ubiquitous presence in natural products and drugs,
the development of new and efficient preparative protocols for
these structures remains an urgent task in organic synthesis.1
Dihydropyran derivatives, which are among the most investigated
heterocycles in the past decade, are widely present in nature-
occurring products.2 Some of dihydropyrans showed important
biological and pharmaceutical activities, and therefore, their syn-
thesis have attracted much attention.3
of 2-aryl-3,4-dihydropyrans, only a few nucleophiles have been
utilized. In this paper, we will mainly focus on the ring-opening
reaction of 2-aryl-3,4-dihydropyrans, in which many nucleo-
philes, such as thiophenols, thiols, benzenesulfinic acid, resorcin, 2-
methylfuran, benzamide and allyltrimethylsilane, were screened.
These reactions along with our previous results offered compre-
hensive information about the ring-opening reaction of 2-aryl-3,4-
dihydropyrans.
Initially, reaction of a 2-aryl-3,4-dihydropyran, 1a, with thio-
phenol, 2a, was investigated, and the results are listed in Table 1. In
the absence of catalyst, no reaction occurred (entry 1). When some
weak acids, such as MnCl2 and boric acid, were used, a product, 3a,
was formed, but owing to the fact that most of the starting mate-
rials keep unaltered, as a result, the yields obtained are rather poor
(entries 2 and 3). These results imply that the ring-opening reaction
is, indeed, possible, and therefore, we screened the other Lewis acid
catalysts in later study. FeCl3 was found to be ineffective for this
reaction because of the formation of a very messy mixture (entry 4).
With other strong Lewis acids, such as Sc(OTf)3, InCl3, ZrCl4 and
Bi(OTf)3, only moderate yields were obtained with a complete
consumption of 1a (entries 5e8). In these cases, many spots were
observed by TLC detection. However, attempt to isolate the by-
product was failed. Interestingly, an exclusive selectivity to 3a
was observed when using MnBr2 as a catalyst. And after 11 h of
Recently, we have described a three-component reaction of
olefins, formaldehyde and b-dicarbonyl compounds, which gener-
ated a variety of 2,5,6-trisubstituted 3,4-dihydropyrans in high
yields.4 This reaction opens a facile method to prepare the dihy-
dropyrans. Therefore, using of these dihydropyrans in organic
synthesis becomes thus a downstream topic for us. Because skel-
etons of the dihydropyrans involve a benzyl ether fragment, that is,
generally unstable in the presence of nucleophile under acidic
condition,5 the dihydropyran could be a valuable substrate in acid-
catalyzed transformations. Out of this consideration, quite recently,
* Corresponding author. Fax: þ86 (0) 27 87 54 45 32; e-mail address: klgyl@
hust.edu.cn (Y. Gu).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.075

M. Li, Y. Gu / Tetrahedron 67 (2011) 8314e8320
8315
Table 1
With the optimized conditions in hand, we probed the scope of
the reaction with respect to both the dihydropyrans and thio-
phenols. As shown in Scheme 1, a variety of dihydropyrans and
thiophenols could be applied in the ring-opening reaction, and the
corresponding products were obtained in good to excellent yields.
Thiols can also be used instead of thiophenol to react with 1a-type
dihydropyran under catalysis of MnBr2 to generate the corre-
sponding ring-opening products in high yields. A reaction in
preparative-scale (20 mmol) was also investigated by using thio-
phenol 2a as substrate, and it was found that the reaction pro-
ceeded uneventfully (Table 1, entry 13), indicating the usefulness of
this method for practical synthesis. It should be noted that because
the formed product contains not only a fragment of 1,3-dicarbonyl
compound, but also a moiety of sulfide, it is thus conceivable that
these products could be useful for organic synthesis.
The mechanism of the ring-opening reaction most likely in-
volves a Lewis acid-assisted formation of a benzylcarbenium and
the following electrophilic reaction with the nucleophile. In order
to get an evidence, we then treated a 2-aryl-3,4-dihydropyran, 1b,
under the reaction condition in the absence of nucleophile. After
6 h of reaction, a styrene derivative, 4a, was obtained in 31% of yield
(Scheme 2). Interestingly, in the presence of MnBr2, the isolated 4a
can react smoothly with thiophenol, 2a, to form the ring-opening
product, 3e, in 81% of yield. This result implies (i) a benzylcarbe-
nium might be, indeed, formed, which can then generate 4a
through a hydrogen transfer pathway; and (ii) 4a might be the
reaction intermediate for the model reaction.
Ring-opening reaction of 1a with 2a in different conditionsa
SH
O
2a (1.5 equiv)
OEt
S
O
catalyst (10 mol %)
o
solvent, 80 C, 11 h
O
OEt
O
1a
3a
Entry
Catalyst
Solvent
Yield%
1
2
3
4
5
6
7
8
d
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
Toluene
1,4-Dioxane
DCE
0
MnCl2
H3BO3
FeCl3
Sc(OTf)3
lnCl3
22
31
10
45
62
55
46
87
Trace
10
29
85
ZrCl4
Bi(OTf)3
MnBr2
MnBr2
MnBr2
MnBr2
MnBr2
9
10
11
12
13b
CH3NO2
a
The reaction was performed in 0.25 mmol scale in 1.0 ml of solvent.
The reaction was performed in 20 mmol scale.
b
reaction at 80 ꢀC, the yield reached to 87% (entry 9). Further in-
vestigation revealed that the solvent also played a key role in
controlling the catalytic activity of MnBr2, and nitromethane was
proved to be an appropriate solvent for this system (entries 9e12).
On the basis of these results, we thus proposed a plausible
mechanism in Fig. 1. In the beginning of the reaction, the dihy-
dropyran was activated by MnBr2 to form a benzylcarbenium (I) via
cleavage of C(2)eO bond,7 which then underwent a hydrogen
R
S
O
S
O
S
O
OEt
OEt
OEt
O
R
O
O
3b, R = OMe (80%)
3c, R = Cl (94%)
3e, R = OMe (99%)
3h (86%)
3f, R = OEt (98%)
t
3d, R = isopropyl (84%)
3g, R = Bu (91%, MnBr2,
20 mol %, 100 oC, 24 h)
MeO
S
O
S
O
S
O
OEt
OEt
OEt
O
O
F
O
3j (90%)
3k (68%, MnBr2, 20 mol %, 24 h)
3i (74%)
S
O
S
O
S
O
1
OEt
OEt
R
2
R
O
R
O
R
O
3p, R1 = OEt, R2 = Me (81%)
3q, R1 = R2 =OMe (90%)
3n, R = H (81%, MnBr2,
3l, R = H (79%, MnBr2,
20 mol %, 100 oC, 24 h)
3m, R = Me (91%)
20 mol %, 100 oC, 24 h)
3o, R = Cl (87%, MnBr2,
20 mol %, 100 oC, 24 h)
Scheme 1. Ring-opening reactions of 2-aryl-3,4-dihydropyrans with thiophenols or thiols catalyzed by MnBr2. Unless otherwise specified, all the reactions were conducted under
the optimized condition in Table 1.

8316
M. Li, Y. Gu / Tetrahedron 67 (2011) 8314e8320
O
solvent proved to be both important for the screening of
nucleophiles.
O
OEt
MnBr2 (10 mol %)
As shown in Scheme 3, benzenesulfinic acid, 5a, can readily
react, in the presence of catalytic amount of InCl3, with dihy-
dropyrans, 1b and 1c, to form the corresponding ring-opening
products, 6a and 6b, in excellent yields. Instead of sulfide, the
formed products, here, contain a fragment of sulfone in the struc-
ture. Although the sulfone product could be theoretically synthe-
sized by means of an oxidation of sulfide that was prepared through
the first ring-opening reaction, the reaction of benzenesulfinic acid
offers a straightforward way for the synthesis of this kind of
sulfone.
OEt
O
o
CH3NO2, 80 C, 6 h
MeO
O
MeO
1b
4a (31%)
2a (1.5 equiv)
S
O
MnBr2 (10 mol %)
4a
o
CH3NO2, 80 C, 11 h
OEt
MeO
O
3e (81%)
Scheme 2. Subdivision of the ring-opening reaction and the intermediate isolated
from the catalytic system.
O
S
OH
O
5a (1.0 equiv)
O
R
InCl3 (10 mol %)
O
S
O
O
OEt
MnBr2
O
CH2Cl2, rt, 11 h
R
O
3e
MeO
MeO
O
MnBr2
MeO
1b, R = OEt
1c, R = OMe
6a, R = OEt (92%)
6b, R = OMe (91%)
1b
MnBr2
O
Scheme 3. Ring-opening reaction of the dihydropyrans, 1b and 1c, with benzene-
sulfinic acid 5a.
S
OH
2a
MnBr2
MeO
O
OEt
Scheme 4 shows a ring-opening reaction of dihydropyran 1c
with a nitrogen-based nucleophile, benzamide 7a. Because of the
poor reactivity of benzamide, a strong Lewis acid, Bi(OTf)3, has to be
used in this case. It should be noted that, in view of the fact that
Bi(OTf)3 is unstable at high temperature,11 the real catalyst here
might be trifluoromethanesulfonic acid (TfOH) that was in situ
generated during the decomposition of Bi(OTf)3. This conjecture
can be verified by a fact that 80% yield could be obtained by using
TfOH as catalyst. Furthermore, the high reaction yield obtained here
implies also that structure of the formed product is quite stable in
the presence of strong acid. And therefore, the observed suscepti-
bility of the model ring-opening reaction in Table 1 toward Lewis
acid catalyst also has to be related to the reactivity of nucleophile.
On the basis of our experience, an empiristic tendency could be
summarized at this stage. That is more reactive the nucleophile is,
more difficult to control the selectivity.
MeO
O
OEt
(I)
2a
O
MnBr2
OEt
MeO
O
4a
Fig. 1. Plausible mechanism of the ring-opening reaction of dihydropyran 1b with 2a.
transfer to form 4a. It should be noted that, in the beginning of the
catalytic cycle, MnBr2 might also coordinate with the carbonyl
group of the ester functionality of 1b, activating indirectly the CeO
bond of ether group, and leading to thus a formation of a benzyl-
carbenium (I). After an atom-economic addition of 2a to 4a, the
final ring-opening product 3e could be formed.8 It should be noted
that, in the presence of a Lewis acid catalyst, (I) could also be di-
rectly trapped with 2a to form the desired product 3e.8b,9 Although
these reaction pathways are both operative for the formation of 4a,
in view of the presence of a ketocarbonyl in the structures of the
intermediate 4a and the formed product 3e, which are also reactive
toward nucleophiles under acidic condition, controlling of the re-
action selectivity is thus a challenge. The use of a weak Lewis acid as
catalyst ensures the selectivity but may also be a reason of in-
sufficient reaction. On the contrary, the reaction over a strong Lewis
acid proceeds rapidly, but suffers from a bad control of the reaction
selectivity. Thanks to the mild acid strength of MnBr2 catalyst, we
are able to make a good balance between the conversion and the
selectivity to the ring-opening product. In addition, the unique
performance of MnBr2 as a Lewis acid catalyst may also be valuable
for other organic transformations, and this point deserves further
investigation.
O
NH2
O
7a (1.5 equiv)
OMe
Bi(OTf)3 (10 mol %)
O
NH
O
o
1,4-dioxane, 100 C, 11 h
O
OMe
MeO
MeO
O
1c
8a (84%)
Scheme 4. Ring-opening reaction of dihydropyran 1c with benzamide 7a.
Carbon-based nucleophiles, such as 2-methylfuran and resorcin,
can also be used in this type of ring-opening reaction. As shown in
Scheme 5, in the presence of MnBr2, the ring-opening reaction of 1c
with 2-methylfuran 9a proceeded exclusively, and the corre-
sponding ring-opening product 10a was obtained in nearly quan-
titative yield. However, in the case of resorcin 11a, only a moderate
yield was obtained. Many other carbon-based nucleophiles might
also be applicable in this reaction, and the study in this line is
underway in our group.
According to this mechanism, other nucleophiles might also
be applicable. We thus explore the generality of this ring-
opening reaction with respect to nucleophiles. In view of the
huge difference on the reactivity of nucleophiles, the reaction
condition has to be optimized for each substrate.10 Catalyst and

M. Li, Y. Gu / Tetrahedron 67 (2011) 8314e8320
8317
O
enesulfinic acid, Sc(OTf)3, Bi(OTf)3, InCl3, 4-hydroxy-6-methyl-2-
pyrone and chloroform-d were purchased from Alfa Aesar Chem-
ical Company. a-Methylstyrene, resorcin, MnBr2, methyl acetoace-
9a (1.5 equiv)
O
tate, ethyl acetoacetate, acetylacetone, FeCl3 (anhydrous), MnCl2
(anhydrous), H3BO3, DMSO, 1,4-dioxane, 1,2-dichloroethane, ace-
tonitrile, nitromethane, DMF, toluene, ethyl acetate, and formal-
dehyde aqueous solution (37 wt %) were purchased from
Sinopharm Chemical Reagents Limited Company (SCRC). 2,5,6-
Trisubstituted 3,4-dihydropyrans were prepared in water accord-
ing to our reported method starting from olefins, 1,3-dicarbonyl
compounds and formaldehyde aqueous solution.4a 1H and 13C
NMR spectra were recorded on a Bruker AV-400. Chemical shifts
are expressed in parts per million relative to Me4Si in CDCl3. IR
spectra were recorded on an FT-IR Bruker (VERTEX 70) using KBr
technology.
MnBr2 (10 mol %)
O
o
CH3NO2, 100 C, 5 h
OMe
O
MeO
O
OH
R
10a (99%)
O
OH
OH
MeO
11a (1.5 equiv)
1b, R = OEt
1c, R = OMe
MnBr2 (10 mol %)
OH
O
o
CH3NO2, 80 C, 11 h
OEt
MeO
O
12a (63%)
2.2. A typical procedure for ring-opening reaction of
dihydropyran 1a with 2a
Scheme 5. Ring-opening reaction of dihydropyrans, 1b and 1c, with 2-methylfuran 9a
and resorcin 11a.
All reactions were conducted in a 10 ml of V-type flask equipped
with triangle magnetic stirring. In a typical reaction, nitromethane
(1.0 ml) was mixed with 1a (65.1 mg, 0.25 mmol), 2a (41.3 mg,
0.38 mmol) and MnBr2 (5.4 mg, 10 mol %) under air. The mixture
was stirred for 11 h at 80 ꢀC. After reaction, the mixture was cooled
to room temperature and the desired product, 3a, was obtained by
preparative TLC using a mixed solution of ethyl acetate and pet.
ether as eluting solvent (the ratio of ethyl acetate/pet. ether is 1/6).
80.6 mg, Yield¼87%. Tests for substrate scope and the reaction of
using other nucleophile were all performed according to an anal-
ogous procedure with above mentioned. The reaction in 20 mmol
was performed also in the same procedure, but the product was
isolated by a silica column chromatography method.
Finally, the reactivity of a silicon-containing nucleophile, allyl-
trimethylsilane, was examined in the ring-opening reaction
(Scheme 6). In this case, the reaction has to be conducted in
dichloromethane at room temperature by using Sc(OTf)3 as cata-
lyst. The obtained product contains not only a double bond but also
a fragment of 1,3-dicarbonyl compound. Therefore, it might be
valuable for organic synthesis.
SiMe3
13a (1.5 equiv)
O
1)
2)
Sc(OTf)3 (20 mol %)
CH2Cl2, rt, 3 h
OEt
O
O
OEt
NaHCO3 aqu. rt. 9 h
2.3. A procedure for treating a dihydropyran 1b in the absence
of nucleophile and the following reaction of 4a with 2a
MeO
MeO
O
1b
14a (55%)
All reactions were conducted in a 10 ml of V-type flask equipped
with triangle magnetic stirring. In a typical reaction, nitromethane
(2.0 ml) was mixed with 1b (138.2 mg, 0.50 mmol) and MnBr2
(10.7 mg, 10 mol %) under air. The mixture was stirred for 6 h at
80 ꢀC. After reaction, the mixture was cooled to room temperature
and a product, 4a, was obtained by preparative TLC using a mixed
solution of ethyl acetate and pet. ether as eluting solvent (the ratio
of ethyl acetate/pet. ether is 1/8). Yield¼31%, 42.8 mg. The obtained
4a was then mixed with 2a (25.6 mg, 0.23 mmol) and MnBr2
(3.3 mg,10 mol %) in 1 ml nitromethane, and then mixture was then
heated at 80 ꢀC for 11 h. At the end of the reaction, 3e was obtained
by preparative TLC isolation procedure (eluting solvent is a mixture
of ethyl acetate and pet. ether, the ratio is v/v¼1/6) in 81% yield
(48.5 mg).
Scheme 6. Ring-opening reaction of dihydropyran 1b with allyltrimethylsilane 13a.
In conclusion, an electrophilic ring-opening reaction of 2-aryl-
3,4-dihydropyran with nucleophile was described. Many nucleo-
philes, such as thiophenols, thiols, benzenesulfinic acid, benza-
mide, 2-methylfuran, resorcin, and allyltrimethylsilane, were all
successfully used in this type of ring-opening reaction. The gener-
ated products contain not only a core structure of the nucleophile,
but also a fragment of 1,3-dicarbonyl compound. The ring-opening
reaction might proceed through (i) a Lewis acid-assisted cleavage of
C(2)eO bond that generates a benzylcarbenium intermediate, and
(ii) the following electrophilic reaction of the reaction intermediate
with a nucleophile. These results offered a complementary in-
formation about the ring-opening reaction of 2-aryl-3,4-
dihydropyran, and demonstrated that many nucleophiles could
be successfully used. The other nucleophiles might also be appli-
cable in this type of ring-opening reaction, and the study in this line
is underway in our group.
2.4. Procedure for ring-opening allylation reaction of
dihydropyran 1b with allyltrimethylsilane 13a
The reaction was conducted in a 10 ml of V-type flask equipped
with triangle magnetic stirring. Dichloromethane (1.0 ml) was
mixed with dihydropyran 1b (69.1 mg, 0.25 mmol), allyl-
trimethylsilane 13a (42.9 mg, 0.38 mmol), and Sc(OTf)3 (24.6 mg,
20 mol %) under air. The mixture was stirred for 3 h at room tem-
perature. After reaction, the reaction mixture was then mixed with
NaHCO3 aqueous solution (2N, 2.0 ml) and stirred for 9 h at room
temperature. Finally, 5.0 ml ofbrinewasadded and then the aqueous
phase was extracted with dichloromethane (5.0 mlꢁ3). The ob-
tained organic phases were then combined together and dried with
anhydrous Na2SO4. After evaporation under reduced pressure, the
desired product,14a, was obtained by preparative TLC using a mixed
2. Experimental section
2.1. General
4-Methylstyrene, 4-fluoro-
a-methylstyrene, tert-butylstyrene,
4-methoxystyrene, 4-ethoxystyrene, thiophenol, 3,5-dimethylthio-
phenol, 2,4-dimethylthiophenol, 4-chlorothiophenol, 4-isopropyl-
thiophenol, 4-methoxythiophenol, 2-methylthiophenolethiol,
benzenemethanethiol, 2-methylfuran, allyltrimethylsilane, benz-

8318
M. Li, Y. Gu / Tetrahedron 67 (2011) 8314e8320
solution of ethyl acetate and pet. ether as eluting solvent (the ratio of
ethyl acetate/pet. ether is 1/8). Yield¼55%, 43.6 mg.
J¼4.4 Hz, 3H), 3.34 (q, J¼6.0 Hz, 1H), 3.97 (q, J¼6.8 Hz, 2H),
4.05e4.18 (m, 3H), 6.77 (td, Ja¼2.0 Hz, Jb¼6.4 Hz, 2H), 7.12 (dd,
Ja¼1.6 Hz, Jb¼8.8 Hz, 2H), 7.15e7.21 (m, 3H), 7.21e7.27 (m, 2H); 13
C
2.5. Spectroscopic data of newly synthesized products
NMR (CDCl3): 14.1, 14.9, 26.1, 26.2, 28.7, 28.8, 33.7, 33.8, 52.6, 52.6,
59.3, 59.4, 61.4, 61.4, 63.4, 114.4, 127.2, 127.2, 128.8, 128.8, 132.5,
132.5, 132.9,133.0,134.8, 134.8, 158.2, 169.4, 169.5, 202.7; IR (cmꢂ1):
3061, 2982, 2938, 1967, 1887, 1742, 1720, 1609, 1510, 1477, 1363,
1248, 1177, 1049, 924, 840, 746, 695; HRMS m/z (ESI) calcd for
C23H28NaO4S [MþNa]þ 423.1606 found 423.1601.
2.5.1. Ethyl
2-acetyl-5-(phenylthio)-5-(p-tolyl)pentanoate
(3a).
Colorless liquid; 1H NMR (CDCl3): 1.22 (dt, Ja¼2.0 Hz, Jb¼7.2 Hz, 3H),
1.73e1.97 (m, 4H), 2.13 (d, J¼4.8 Hz, 3H), 2.29 (s, 3H), 3.34 (q,
J¼6.4 Hz, 1H), 4.06e4.18 (m, 3H), 7.06 (d, J¼8.0 Hz, 2H), 7.11 (d,
J¼8.0 Hz, 2H), 7.15e7.22 (m, 3H), 7.23e7.28 (m, 2H); 13C NMR
(CDCl3): 14.1, 21.1, 26.1, 26.2, 28.7, 28.8, 33.7, 33.8, 52.9, 53.0, 59.4,
59.4, 61.5, 61.5, 127.1, 127.1, 127.6, 128.7, 129.2, 132.3, 132.4, 134.9,
134.9, 137.0, 138.1, 138.2, 169.4, 169.5, 202.7; IR (cmꢂ1): 3053, 3020,
2980, 2925, 2866, 1738, 1716, 1642, 1583, 1512, 1443, 1359, 1243,
1145, 1023, 821, 742, 692; HRMS m/z (ESI) calcd for C22H26NaO3S
[MþNa]þ 393.1500 found 393.1495.
2.5.7. Ethyl 2-acetyl-5-(4-(tert-butyl)phenyl)-5-(phenylthio)penta-
noate (3g). Colorless liquid; 1H NMR (CDCl3): 1.20 (t, J¼7.2 Hz, 3H),
1.29 (s, 9H), 1.64e2.00 (m, 4H), 2.11 (d, J¼3.6 Hz, 3H), 3.34 (q,
J¼7.6 Hz, 1H), 4.12 (quint, J¼6.8 Hz, 3H), 7.13e7.22 (m, 5H),
7.23e7.30 (m, 4H); 13C NMR (CDCl3): 14.1, 26.1, 26.2, 28.7, 28.8,
31.4, 33.7, 33.8, 34.5, 52.8, 52.8, 59.4, 59.5, 61.4, 61.5, 125.5, 127.1,
127.1, 127.4, 128.7, 128.7, 132.0, 132.3, 132.3, 135.0, 135.0, 138.0,
138.0, 150.2, 169.5, 169.5, 202.8; IR (cmꢂ1): 3056, 2965, 2905,
2869, 1739, 1717, 1643, 1584, 1470, 1362, 1146, 1024, 842, 744, 692,
570; HRMS m/z (ESI) calcd for C25H23NaO3S [MþNa]þ 435.1970
found 435.1964.
2.5.2. Ethyl
2-acetyl-5-[(4-methoxyphenyl)thio]-5-(p-tolyl)penta-
noate (3b). Colorless liquid; 1H NMR (CDCl3): 1.21 (dt, Ja¼1.2 Hz,
Jb¼7.2 Hz, 3H), 1.70e1.98 (m, 4H), 2.13 (d, J¼2.4 Hz, 3H), 2.29 (s, 3H),
3.35 (q, J¼5.6 Hz, 1H), 3.73 (s, 3H), 3.91 (t, J¼8.0 Hz, 1H), 4.13 (q,
J¼6.8 Hz, 2H), 6.72 (d, J¼8.4 Hz, 2H), 7.04 (t, J¼8.8 Hz, 4H), 7.17 (d,
J¼8.4 Hz, 2H); 13C NMR (CDCl3): 14.1, 21.1, 26.2, 26.3, 28.7, 28.8,
33.2, 33.3, 54.1, 54.1, 55.3, 59.4, 59.5, 61.4, 114.2, 124.7, 127.7, 129.1,
135.9,135.9,136.8, 138.3, 138.4, 159.6, 169.5, 169.5, 202.8; IR (cmꢂ1):
2938, 2869, 2837, 1738, 1716, 1591, 1494, 1454, 1360, 1285, 1245,
1173, 1147, 1030, 826; HRMS m/z (ESI) calcd for C23H28NaO4S
[MþNa]þ 423.1606 found 423.1601.
2.5.8. Ethyl 2-acetyl-5-(p-tolyl)-5-(o-tolylthio)pentanoate (3h).
Colorless liquid; 1H NMR (CDCl3): 1.21 (dt, Ja¼2.4 Hz, Jb¼7.2 Hz, 3H),
1.69e1.99 (m, 4H), 2.12 (d, J¼4.8 Hz, 3H), 2.29 (s, 3H), 3.34 (q,
J¼6.8 Hz,1H), 4.04 (dd, Ja¼6.0 Hz, Jb¼8.8 Hz, 1H), 4.13 (tq, Ja¼2.0 Hz,
Jb¼7.2 Hz, 2H), 7.01e7.09 (m, 3H), 7.09e7.14 (m, 3H), 7.21e7.26 (m,
1H); 13C NMR (CDCl3): 14.1, 20.7, 21.1, 26.2, 26.2, 28.7, 28.8, 33.8,
33.9, 52.2, 52.2, 59.4, 59.5, 61.4, 126.3, 127.0, 127.1, 127.6, 127.6,
129.2, 130.2, 132.3, 132.4, 134.2, 134.3, 137.0, 138.1, 138.2, 139.8,
139.9, 169.5, 169.5, 202.7; IR (cmꢂ1): 3057, 2982, 2927, 2869, 1739,
1717, 1644, 1514, 1456, 1361, 1245, 1209, 1146, 1049, 1023, 821, 750;
HRMS m/z (ESI) calcd for C23H28NaO3S [MþNa]þ 407.1657 found
407.1651.
2.5.3. Ethyl 2-acetyl-5-[(4-chlorophenyl)thio]-5-(p-tolyl)pentanoate
(3c). Colorless liquid; 1H NMR (CDCl3): 1.23 (t, J¼6.8 Hz, 3H),
1.69e1.97 (m, 4H), 2.14 (d, J¼5.2 Hz, 3H), 2.29 (s, 3H), 3.35 (q,
J¼6.8 Hz, 1H), 4.04 (dd, Ja¼2.4 Hz, Jb¼7.6 Hz, 1H), 4.10e4.19 (m, 2H),
7.04e7.11 (m, 4H), 7.12e7.18 (m, 4H); 13C NMR (CDCl3): 14.1, 21.1,
26.1, 26.2, 28.8, 28.8, 33.6, 33.7, 53.2, 53.2, 59.3, 59.4, 61.5, 61.5,
127.6, 128.8, 129.3, 133.2, 133.3, 133.3, 133.8, 133.9, 137.2, 137.8,
137.9, 169.4, 169.5, 202.6; IR (cmꢂ1): 2981, 2930, 2866, 1737, 1715,
1644, 1512, 1474, 1450, 1359, 1243, 1145, 1095, 1013, 819; HRMS m/z
(ESI) calcd for C22H25ClNaO3S [MþNa]þ 427.1111 found 427.1105.
2.5.9. Ethyl 2-acetyl-5-[(2,4-dimethylphenyl)thio]-5-(p-tolyl)penta-
noate (3i). Colorless liquid; 1H NMR (CDCl3): 1.21 (dq, Ja¼3.6 Hz,
Jb¼6.8 Hz, 3H), 1.72e1.99 (m, 4H), 2.12 (d, J¼4.0 Hz, 3H), 2.25 (s,
6H), 2.29 (s, 3H), 3.33 (q, J¼6.8 Hz, 1H), 3.96 (dd, Ja¼6.0 Hz,
Jb¼8.4 Hz, 1H), 4.09e4.18 (m, 2H), 6.86 (d, J¼8.0 Hz, 1H), 6.95 (s,
1H), 7.05 (d, J¼8.0 Hz, 2H), 7.09 (dd, Ja¼2.0 Hz, Jb¼8.4 Hz, 2H),
7.14 (d, J¼7.6 Hz, 1H); 13C NMR (CDCl3): 14.1, 20.7, 21.0, 21.1, 26.2,
26.3, 28.7, 28.8, 33.6, 33.8, 52.6, 52.7, 59.4, 59.5, 61.4, 61.4, 127.0,
127.6, 129.2, 130.4, 130.4, 131.1, 133.5, 133.6, 136.9, 137.3, 137.4,
138.3, 138.3, 140.4, 140.4, 169.5, 169.5, 202.8; IR (cmꢂ1): 2923,
2867, 1738, 1716, 1642, 1451, 1359, 1241, 1146, 1056, 1020, 813;
HRMS m/z (ESI) calcd for C24H30NaO3S [MþNa]þ 421.1813 found
421.1827.
2.5.4. Ethyl 2-acetyl-5-[(4-isopropylphenyl)thio]-5-(p-tolyl)penta-
noate (3d). Colorless liquid; 1H NMR (CDCl3): 1.18e2.04 (m, 9H),
1.72e1.97 (m, 4H), 2.12 (d, J¼4.4 Hz, 3H), 2.30 (s, 3H), 2.84 (sept,
J¼7.2 Hz, 1H), 3.33 (q, J¼6.4 Hz, 1H), 4.03 (dd, Ja¼4.8 Hz, Jb¼8.0 Hz,
1H), 4.08e4.17 (m, 2H), 7.02e7.13 (m, 6H), 7.18 (d, J¼8.4 Hz, 2H); 13C
NMR (CDCl3): 14.1, 21.2, 23.9, 26.2, 26.2, 28.7, 33.7, 33.8, 33.8, 53.1,
53.2, 59.4, 59.5, 61.4, 126.9, 127.6, 127.7, 129.2, 131.5, 131.6, 132.8,
132.9, 136.9, 138.3, 138.4, 148.2,148.2,169.5, 169.5, 202.8; IR (cmꢂ1):
2963, 2872, 1741, 1719, 1646, 1456, 1362, 1147, 1018, 828; HRMS m/z
(ESI) calcd for C25H32NaO3S [MþNa]þ 435.1970 found 435.1964.
2.5.10. Ethyl 2-acetyl-5-[(3,5-dimethylphenyl)thio]-5-(p-tolyl)penta-
noate (3j). Colorless liquid; 1H NMR (CDCl3): 1.21 (dt, Ja¼3.2 Hz,
Jb¼7.2 Hz, 3H),1.72e1.97 (m, 4H), 2.12 (d, J¼4.8 Hz, 3H), 2.22 (s, 3H),
2.30 (s, 3H), 3.33 (q, J¼8.0 Hz, 1H), 4.07 (dt, Ja¼2.4 Hz, Jb¼8.4 Hz,
1H), 4.10e4.18 (m, 2H), 6.80 (s, 1H), 6.87 (s, 2H), 7.07 (d, J¼8.0 Hz,
2H), 7.12 (dd, Ja¼1.2 Hz, Jb¼8.0 Hz, 2H); 13C NMR (CDCl3): 14.1, 21.1,
21.2, 26.2, 26.2, 28.7, 28.8, 33.7, 33.8, 52.6, 59.4, 61.4, 127.7, 128.9,
128.9, 129.2, 129.8, 129.9, 134.3, 134.3, 136.9, 138.2, 138.3, 169.5,
169.5, 202.8; IR (cmꢂ1): 2923, 2861, 1739, 1587, 1452, 1364, 1216,
1146, 1021, 849, 687; HRMS m/z (ESI) calcd for C24H30NaO3S
[MþNa]þ 421.1813 found 421.1808.
2.5.5. Ethyl 2-acetyl-5-(4-methoxyphenyl)-5-(phenylthio)pentanoate
(3e). Colorless liquid; 1H NMR (CDCl3): 1.21 (dt, Ja¼2.8 Hz,
Jb¼7.2 Hz, 3H), 1.72e1.97 (m, 4H), 2.13 (d, J¼4.4 Hz, 3H), 3.34 (q,
J¼6.0 Hz, 1H), 3.75 (s, 3H), 4.06e4.18 (m, 3H), 6.78 (td, Ja¼2.4 Hz,
Jb¼8.8 Hz, 2H), 7.13 (dd, Ja¼1.6 Hz, Jb¼8.8 Hz, 2H), 7.16e7.22 (m, 3H),
7.22e7.28 (m, 2H); 13C NMR (CDCl3): 14.1, 26.1, 26.2, 28.8, 28.8, 33.7,
33.8, 52.6, 52.6, 55.2, 59.3, 59.4, 61.5, 113.9, 127.2, 127.2, 128.7, 128.8,
132.5, 132.5, 133.1, 133.2, 134.7, 134.8, 158.8, 169.4, 169.5, 202.7; IR
(cmꢂ1): 3060, 2960, 2937, 2837, 1738, 1716, 1608, 1510, 1454, 1360,
1303, 1249, 1176, 1035, 835, 744, 692; HRMS m/z (ESI) calcd for
C22H26NaO4S [MþNa]þ 409.1449 found 409.1444.
2.5.11. Ethyl 2-acetyl-5-(4-fluorophenyl)-5-((4-methoxyphenyl)thio)
hexanoate (3k). Colorless liquid; 1H NMR (CDCl3): 1.25 (dt,
Ja¼2.8 Hz, Jb¼7.2 Hz, 3H), 1.52e1.67 (m, 4H), 1.71e1.92 (m, 2H),
2.02e2.14 (m, 1H), 2.17 (d, J¼14.4 Hz, 3H), 3.33 (q, J¼6.0 Hz, 1H),
3.75 (s, 3H), 4.14e4.22 (m, 2H), 6.70 (td, Ja¼2.4 Hz, Jb¼8.8 Hz, 2H),
2.5.6. Ethyl 2-acetyl-5-(4-ethoxyphenyl)-5-(phenylthio)pentanoate
(3f). Colorless liquid; 1H NMR (CDCl3): 1.20 (dt, Ja¼2.4 Hz,
Jb¼7.2 Hz, 3H), 1.37 (t, J¼6.8 Hz, 3H), 1.72e1.98 (m, 4H), 2.12 (d,

M. Li, Y. Gu / Tetrahedron 67 (2011) 8314e8320
8319
6.94 (dt, Ja¼1.2 Hz, Jb¼8.8 Hz, 2H), 6.98e7.03 (m, 2H), 7.23e7.29 (m,
2H); 13C NMR (CDCl3): 14.1, 23.4, 23.5, 25.1, 25.2, 28.8, 28.9, 39.3,
39.4, 53.4, 55.2, 59.8, 61.5, 113.8, 113.9, 114.6, 114.6, 114.8, 114.8,
122.4, 128.7, 128.8, 138.4, 138.5, 139.8, 139.9, 160.1, 160.4, 162.6,
169.5, 169.5, 202.7; IR (cmꢂ1): 3066, 2974, 2940, 2838, 2532, 2045,
1892,1739,1717,1594,1498,1461,1405,1369,1285,1246,1166,1102,
1028, 830, 737, 644, 527; HRMS m/z (ESI) calcd for C23H27FNaO4S
[MþNa]þ 441.1512 found 441.1506.
Ja¼2.0 Hz, Jb¼7.2 Hz, 1H), 4.16 (double quint, Ja¼2.0 Hz, Jb¼6.8 Hz,
2H), 7.10 (d, J¼8.0 Hz, 2H), 7.17 (d, J¼8.0 Hz, 2H); 13C NMR (CDCl3):
14.1, 14.1, 21.1, 25.8, 25.9, 26.0, 26.3, 28.7, 28.8, 33.2, 33.8, 34.6, 34.6,
42.5, 42.5, 47.3, 47.4, 59.5, 59.5, 61.4, 61.4, 127.5, 127.5, 129.2, 136.6,
139.6, 139.7, 169.5, 169.6, 202.9; IR (cmꢂ1): 2928, 2852, 1738, 1716,
1643, 1510, 1449, 1359, 1242, 1145, 1021, 953, 887, 817, 779, 525;
HRMS m/z (ESI) calcd for C22H32NaO3S [MþNa]þ 399.1970 found
399.1964.
2.5.12. Methyl 2-acetyl-5-(benzylthio)-5-phenylpentanoate (3l).
Colorless liquid; 1H NMR (CDCl3): 1.62e1.94 (m, 4H), 2.12 (d,
J¼9.6 Hz, 3H), 3.30 (quint, J¼7.6 Hz, 1H), 3.38 (dd, Ja¼4.0 Hz,
Jb¼13.6 Hz, 1H), 3.50 (d, J¼13.6 Hz, 1H), 3.58 (dt, Ja¼1.6 Hz,
Jb¼6.8 Hz, 1H), 3.67 (d, J¼6.0 Hz, 3H), 7.17e7.22 (m, 2H), 7.22e7.29
(m, 5H), 7.29e7.36 (m, 3H); 13C NMR (CDCl3): 26.1, 26.2, 28.8. 28.9,
33.9, 34.0, 35.4, 35.4, 48.7, 48.7, 52.5, 59.1, 127.0, 127.4, 128.0, 128.1,
128.4, 128.5, 128.5, 128.6, 128.6, 129.0, 138.2, 138.2, 141.8, 141.9,
169.9, 169.9, 202.7; IR (cmꢂ1): 3074, 2965, 2905, 2869. 1739, 1717,
1643, 1470, 1362, 1270, 1178, 1147, 1024, 842, 744, 692, 570; HRMS
m/z (ESI) calcd for C21H24NaO3S [MþNa]þ 379.1344 found 379.1338.
2.5.17. Methyl
2-acetyl-5-(cyclohexylthio)-5-(4-methoxyphenyl)
pentanoate (3q). Colorless liquid; 1H NMR (CDCl3): 1.16e1.23 (m,
4H), 1.51e194 (m, 10H), 2.16 (d, J¼9.2 Hz, 3H), 2.28e2.38 (m, 1H),
3.35e3.40 (m, 1H), 3.70 (d, 6.8 Hz, 3H), 3.79e3.91 (m, 4H), 6.84
(d, J¼8.4 Hz, 2H), 7.20 (d, J¼8.4 Hz, 2H); 13C NMR: 25.7, 25.8,
25.9, 26.2, 28.7, 28.8, 33.2, 33.8, 34.5, 34.6, 42.4, 46.9, 47.0, 52.4,
52.5, 55.2, 59.1, 59.2, 113.8, 128.5, 134.5, 134.6, 158.5, 169.9,
170.0, 202.7, 202.8; IR (cmꢂ1): 3433, 2999, 2929, 2851, 1744,
1716, 1609, 1510, 1446, 1358, 1301, 1248, 1176, 1147, 1035, 834,
544; HRMS m/z (ESI) calcd for C21H30NaO4S [MþNa]þ 401.1762
found 401.1753.
2.5.13. Ethyl 2-acetyl-5-(benzylthio)-5-(p-tolyl)pentanoate (3m).
Colorless liquid; 1H NMR (CDCl3): 1.22 (dq, Ja¼2.0 Hz, Jb¼7.2 Hz,
3H), 1.63e1.90 (m, 4H), 2.12 (d, J¼8.8 Hz, 3H), 2.34 (s, 3H), 3.27
(quint, J¼8.4 Hz, 1H), 3.38 (dd, Ja¼3.6 Hz, Jb¼13.2 Hz, 1H), 3.50 (d,
J¼13.6 Hz, 1H), 3.56 (dt, Ja¼2.0 Hz, Jb¼7.2 Hz, 1H), 4.13 (dq,
Ja¼3.2 Hz, Jb¼6.8 Hz, 2H), 7.11e7.18 (m, 4H), 7.21 (dt, Ja¼1.2 Hz,
Jb¼6.8 Hz, 3H), 7.24e7.31 (m, 2H); 13C NMR (CDCl3): 14.1, 14.1, 21.2,
26.1, 26.2, 28.7, 28.8, 33.9, 34.0, 35.3, 35.4, 48.4, 48.4, 59.3, 59.3,
61.4, 126.9, 127.9, 128.4, 129.0, 129.3, 136.9, 138.3, 138.4, 138.7, 138.8,
169.4, 169.5, 202.8, 202.8; IR (cmꢂ1): 3029, 2982, 2925, 1740, 1718,
1454, 1361, 1244, 1151, 1030, 819, 769, 702; HRMS m/z (ESI) calcd for
C23H28NaO3S [MþNa]þ 407.1657 found 407.1651.
2.5.18. (E)-Ethyl 2-acetyl-5-(4-methoxyphenyl)pent-4-enoate
(4a). White solid, mp¼41e42 ꢀC; 1H NMR (CDCl3): 1.25 (t,
J¼6.8 Hz, 3H), 2.25 (s, 3H), 2.72 (t, J¼7.2 Hz, 2H), 3.57 (t, J¼7.6 Hz,
1H), 3.79 (s, 3H), 4.19 (q, J¼7.2 Hz, 2H), 5.96 (dt, Ja¼15.6 Hz,
Jb¼7.6 Hz,1H), 6.39 (d, J¼15.6 Hz,1H), 6.82 (d, J¼8.4 Hz, 2H), 7.24 (d,
J¼8.4 Hz, 2H); 13C NMR: 14.1, 29.2, 31.5, 55.2, 59.7, 61.4, 113.9, 123.4,
127.3, 129.8, 132.1, 159.0, 169.2, 202.5; IR (cmꢂ1): 3414, 3031, 2986,
2965, 2916, 2842,1736,1710,1607,1511,1457,1422,1367,1303,1251,
1217, 1175, 1143, 1030, 974, 838, 795; HRMS m/z (ESI) calcd for
C16H20NaO4 [MþNa]þ 299.1259 found 299.1256.
2.5.19. Ethyl 2-acetyl-5-(4-methoxyphenyl)-5-(phenylsulfonyl)pen-
tanoate (6a). Colorless liquid; 1H NMR (CDCl3): 1.24 (dt, Ja¼7.2 Hz,
Jb¼4.8 Hz, 3H); 1.67e1.74 (m, 2H), 1.99e2.20 (m, 4H), 2.32e2.36
(m, 1H), 3.41 (t, J¼6.4 Hz, 1H), 3.76 (s, 3H), 3.98e4.03 (m, 1H), 4.16
(m, 2H), 6.75 (d, J¼8.8 Hz, 2H), 6.98 (d, J¼8.8 Hz, 2H), 7.37 (t,
J¼8.0 Hz, 2H), 7.51 (m, 3H); 13C NMR: 14.0, 19.1, 25.0, 25.1, 25.2,
25.3, 28.9, 29.0, 30.5, 55.2, 59.0, 61.5, 65.5, 114.0, 123.1, 123.1, 123.2,
128.6, 128.8, 130.9, 133.4, 137.1, 160.0, 169.0, 169.1, 202.1; IR
(cmꢂ1): 3064, 3036, 2962, 2936, 2839, 1737, 1713, 1609, 1513, 1446,
1362, 1298, 1253, 1180, 1145, 1084, 1031, 843, 724, 689, 607; HRMS
m/z (ESI) calcd for C22H26NaO6S [MþNa]þ 441.1348 found
441.1331.
2.5.14. Ethyl 2-acetyl-5-(benzylthio)-5-phenylhexanoate
(3n). Colorless liquid; 1H NMR (CDCl3): 1.23 (q, J¼7.2 Hz, 3H),
1.55e1.71 (m, 1H), 1.74 (d, J¼1.6 Hz, 3H), 1.86e1.88 (m, 1H),
1.88e2.06 (m, 2H), 2.13 (d, J¼16.8 Hz, 3H), 3.23e3.31 (m, 2H), 3.43
(d, J¼12.0 Hz, 1H), 4.10e4.21 (m, 2H), 7.09e7.14 (m, 2H), 7.16 (td,
Ja¼1.2 Hz, Jb¼6.8 Hz, 1H), 7.18e7.27 (m, 3H), 7.30e7.38 (m, 2H),
7.50e7.59 (m, 2H); 13C NMR (CDCl3): 14.1, 14.2, 23.4, 26.1, 26.2, 28.8,
28.9, 33.9, 34.0, 39.9, 40.0, 52.0, 52.0, 59.8, 61.4, 61.5, 125.8, 126.8,
126.8, 127.1, 127.2, 128.2, 128.2, 128.3, 128.3, 128.4, 129.0, 138.0,
138.0, 144.2, 144.3, 169.4, 169.5, 202.8; IR (cmꢂ1): 3086, 3061, 3029,
2977, 2936, 2873, 1952, 1885, 1739, 1717, 1603, 1450, 1360, 1243,
1206,1154,1097,1070,1028, 860, 763, 700; HRMS m/z (ESI) calcd for
C23H28NaO3S [MþNa]þ 407.1657 found 407.1651.
2.5.20. Methyl
2-acetyl-5-(4-methoxyphenyl)-5-(phenylsulfonyl)
pentanoate (6b). Colorless liquid; 1H NMR (CDCl3): 1.71e1.77 (m,
2H), 2.05e2.14 (m, 1H), 2.15 (d, J¼4.0 Hz, 3H), 2.31e2.37 (m, 1H),
3.44 (dt, Ja¼1.6 Hz, Jb¼7.2 Hz, 1H); 3.70 (d, J¼3.2 Hz, 3H), 3.76 (s,
3H), 3.98e4.03 (m, 1H), 6.75 (d, J¼8.4 Hz, 2H), 6.98 (d, J¼8.4 Hz,
2H), 7.36e7.40 (m, 2H), 7.48e7.50 (m, 3H); IR (cmꢂ1): 3063, 3003,
2955, 2841,1741,1715,1610,1513,1445,1360,1297, 1253, 1145,1083,
1032, 844, 725, 690, 607, 563, 527; HRMS m/z (ESI) calcd for
C21H24NaO6S [MþNa]þ 427.1191 found 427.1186.
2.5.15. Ethyl 2-acetyl-5-(benzylthio)-5-(4-chlorophenyl)hexanoate
(3o). Colorless liquid; 1H NMR (CDCl3): 1.25 (q, J¼7.2 Hz, 3H),
1.54e1.68 (m, 1H), 1.71 (d, J¼1.6 Hz, 3H), 1.74e1.84 (m, 1H),
1.85e1.97 (m, 2H), 2.16 (d, J¼12.8 Hz, 3H), 3.23e3.32 (m, 2H), 3.45
(d, J¼12.0 Hz, 1H), 4.17 (double quint, Ja¼0.8 Hz, Jb¼7.2 Hz, 2H),
7.09e7.14 (m, 2H), 7.15e7.26 (m, 3H), 7.30 (td, Ja¼2.4 Hz, Jb¼9.6 Hz,
2H), 7.45 (td, Ja¼2.4 Hz, Jb¼9.6 Hz, 2H); 13C NMR (CDCl3): 14.1, 14.1,
23.3, 26.0, 26.1, 28.9, 29.0, 33.9, 34.0, 39.9, 40.0, 51.5, 51.5, 59.6, 59.7,
61.5, 61.5, 126.9, 128.4, 128.4, 128.4, 128.6, 128.7, 128.9, 132.5, 137.7,
137.7, 143.0, 143.1, 169.4, 169.4, 202.6; IR (cmꢂ1): 3085, 3062, 3029,
2976, 2934, 2873, 1739, 1717, 1645, 1601, 1488, 1454, 1397, 1369,
1258, 1151, 1096, 1012, 831, 710, 697; HRMS m/z (ESI) calcd for
C23H27ClNaO3S [MþNa]þ 441.1267 found 441.1262.
2.5.21. Ethyl 2-acetyl-5-benzamido-5-(4-methoxyphenyl)pentanoate
(8a). Colorless liquid; 1H NMR (CDCl3): 1.26 (dt, Ja¼2.0 Hz,
Jb¼7.2 Hz, 3H), 1.72 (m, 1H), 1.90 (m, 3H), 2.20 (s, 3H), 3.51 (dt,
Ja¼20.4 Hz, Jb¼6.4 Hz, 1H), 3.78 (s, 3H), 4.19 (q, J¼7.2 Hz, 2H), 5.10
(m, 1H), 6.55 (t, J¼6.8 Hz, 1H), 6.87 (d, J¼8.4 Hz, 2H), 7.27 (d,
J¼7.6 Hz, 2H), 7.46 (m, 3H), 7.77 (d, J¼7.2 Hz, 2H); 13C NMR: 13.7,
14.0, 19.1, 24.6, 24.7, 29.0, 30.5, 33.4, 52.9, 53.2, 55.3, 58.9, 59.0, 61.5,
65.5, 114.2, 126.8, 126.9, 127.7, 127.8, 128.5, 128.8, 130.9, 131.5, 132.3,
133.6, 133.7, 134.4, 159.0, 166.7, 166.8, 169.5, 169.6, 203.0, 203.1;
IR(cmꢂ1): 3308, 3062, 2959, 2934, 2871, 2837,1732,1714,1637,1611,
1532, 1514, 1488, 1461, 1359, 1280, 1248, 1179, 1149, 1032, 833, 696,
2.5.16. Ethyl 2-acetyl-5-(cyclohexylthio)-5-(p-tolyl)pentanoate (3p).
Colorless liquid; 1H NMR (CDCl3): 1.10e1.36 (m, 8H), 1.44e1.57 (m,
1H), 1.58e1.86 (m, 6H), 1.86e1.99 (m, 2H), 2.16 (d, J¼8.0 Hz, 3H),
2.30e2.39 (m, 4H), 3.35 (dq, Ja¼1.6 Hz, Jb¼6.8 Hz, 1H), 3.79 (dt,

8320
M. Li, Y. Gu / Tetrahedron 67 (2011) 8314e8320
556; HRMS m/z (ESI) calcd for C23H27NNaO5S [MþNa]þ 420.1787
stuff members in the Analytical and Testing Center of HUST, for
their contributions to our works.
found 420.1783.
2.5.22. Methyl 2-acetyl-5-(4-methoxyphenyl)-5-(5-methylfuran-2-
yl)pentanoate (10a). Colorless liquid; 1H NMR (CDCl3): 1.76e1.85
(m, 3H), 1.97e2.05 (m, 1H), 2.15 (d, J¼7.2 Hz, 3H), 2.20 (s, 3H), 3.40
(t, J¼7.2 Hz,1H), 3.70 (d, J¼2.4 Hz, 3H), 3.76 (s, 3H), 3.80 (t, J¼7.2 Hz,
1H), 5.83 (s, 1H), 5.87 (q, J¼2.8 Hz, 1H), 6.82 (d, J¼8.8 Hz, 2H), 7.13
(dd, Ja¼2.0 Hz, Jb¼8.4 Hz, 2H); 13C NMR: 13.5, 26.4, 28.7, 32.5, 32.6,
44.3, 52.3, 55.2, 59.4, 105.8, 106.0, 113.9, 128.7, 134.3, 134.4, 150.8,
155.6, 155.7, 158.3, 170.0, 170.1, 202.8, 202.9; IR (cmꢂ1): 3102, 3000,
2953, 2927, 2868, 2838, 1743, 1715, 1611, 1562, 1512, 1439, 1358,
1299, 1248, 1216, 1178, 1148, 1032, 837, 786, 540; HRMS m/z (ESI)
calcd for C20H24NaO5 [MþNa]þ 367.1521 found 367.1512.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.08.075.
References and notes
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phenyl)pentanoate (12a). Colorless liquid; 1H NMR (CDCl3): 1.20
(t, J¼7.2 Hz, 3H), 1.85 (m, 4H), 2.13 (d, 3.6 Hz, 3H), 3.46 (dd,
Ja¼16.4 Hz, Jb¼6.8 Hz, 1H), 4.12 (m, 3H), 4.12 (t, J¼7.2 Hz, 3H), 6.26
(s, 1H), 6.34 (dd, Ja¼14.8 Hz, Jb¼8.4 Hz, 2H), 6.58 (s, 1H), 6.76 (d,
J¼8.4 Hz, 2H), 7.12 (d, J¼8.4 Hz, 2H); 13C NMR: 13.7, 14.0, 14.1, 19.1,
26.6, 26.7, 28.8, 28.9, 30.5, 32.5, 42.1, 42.3, 55.2, 59.6, 59.7, 60.7, 61.8,
65.9, 103.3, 107.6, 107.7, 107.8, 113.8, 123.1, 123.3, 128.6, 128.8, 128.9,
130.3, 131.1, 136.2, 136.4, 154.3, 154.4, 154.9, 157.0, 157.7, 170.2, 170.3,
204.9; IR (cmꢂ1): 3401, 3033, 2959, 2935, 2870, 2837, 1727, 1699,
1607, 1511, 1456, 1369, 1302, 1246, 1212, 1178, 1149, 1112, 1033, 974,
910, 839, 732, 632, 552; HRMS m/z (ESI) calcd for C22H26NaO6
[MþNa]þ 409.1627 found 409.1619.
ꢀ
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2.5.24. Ethyl 2-acetyl-5-(4-methoxyphenyl)oct-7-enoate (14a).
Colorless liquid; 1H NMR (CDCl3): 1.24 (dt, Ja¼3.2 Hz, Jb¼7.2 Hz, 3H),
1.37e1.58 (m, 1H), 1.58e1.80 (m, 3H), 2.13 (d, J¼8.4 Hz, 3H), 2.31 (t,
J¼6.8 Hz, 2H), 2.50e2.61 (m, 1H), 3.32 (quint, J¼7.6 Hz, 1H), 3.78 (s,
3H), 4.11e4.20 (m, 2H), 4.90 (s, 0.5H), 4.92 (d, J¼0.4 Hz, 1H), 4.97 (s,
0.5H), 5.57e5.69 (m, 1H), 6.83 (td, Ja¼3.2 Hz, Jb¼7.6 Hz, 2H), 7.06 (d,
J¼8.4 Hz, 2H); 13C NMR: 14.1, 26.1, 26.3, 28.5, 28.8, 33.3, 33.6, 41.4,
41.5, 44.7, 44.9, 55.2, 59.8, 60.0, 61.3, 61.3, 113.8, 116.1, 128.5, 136.3,
136.3, 136.8, 158.0, 169.7, 169.8, 203.2; IR (cmꢂ1): 3072, 2976, 2956,
2921, 2838,1738,1714,1640,1610,1511,1451,1361,1298,1246,1206,
1178, 1148, 1119, 1035, 914, 831, 550, 419; HRMS m/z (ESI) calcd for
C19H26O4 [M]þ 318.1831 found 318.1844.
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Financial support from National Natural Science Foundation of
China (20903042), the Program for new Century Excellent Talents
in the University of China (NCET-10-0383) and Chutian Scholar
Program of the Hubei provincial government are acknowledged.
The authors are also grateful for Ms. Ping Liang and all the other