A convenient one-pot synthesis of 2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one derivatives and their further transformations

Article abstract of DOI:10.1016/j.tet.2008.04.020

The trifluoromethyl containing heterocycles, 2-hydroxy-4-aryl-3-(thien-2-oyl)-2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one derivatives 4, were synthesized via a one-pot three-component reaction of aldehyde 1 with 1,3-cyclohexanedione 2 and 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione 3 in the presence of a catalytic amount of Et₃N. The effect of bases and solvents on the reaction efficiency and yield was briefly investigated. Treatment of 4 with an excess amount of NH₄OAc in ethanol afforded 2-trifluoromethyl-1H-quinolin-5-one derivatives 5. Refluxing of 4 with TsOH in CHCl₃ gave the corresponding dehydrated products 8.

Full text of DOI:10.1016/j.tet.2008.04.020

Tetrahedron 64 (2008) 5728–5735
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Tetrahedron
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A convenient one-pot synthesis of 2-(trifluoromethyl)-3,4,7,8-tetrahydro-
2H-chromen-5(6H)-one derivatives and their further transformations
,
b
,
a
a
b
b
,
c
Shaodi Song a, Liping Song a , Baifan Dai , Hai Yi , Guifang Jin , Shizheng Zhu , Min Shao
*
*
a Department of Chemistry, School of Science, Shanghai University, No. 99, Shangda Road, Shanghai 200444, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
c Instrumental Analysis and Research Center, Shanghai University, Shanghai 200444, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The trifluoromethyl containing heterocycles, 2-hydroxy-4-aryl-3-(thien-2-oyl)-2-(trifluoromethyl)-
3,4,7,8-tetrahydro-2H-chromen-5(6H)-one derivatives 4, were synthesized via a one-pot three-compo-
nent reaction of aldehyde 1 with 1,3-cyclohexanedione 2 and 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-
dione 3 in the presence of a catalytic amount of Et3N. The effect of bases and solvents on the reaction
efficiency and yield was briefly investigated. Treatment of 4 with an excess amount of NH4OAc in ethanol
afforded 2-trifluoromethyl-1H-quinolin-5-one derivatives 5. Refluxing of 4 with TsOH in CHCl3 gave the
corresponding dehydrated products 8.
Received 24 January 2008
Received in revised form 2 April 2008
Accepted 7 April 2008
Available online 9 April 2008
Keywords:
One-pot multi-component reaction
Fluorinated heterocycles
Trifluoromethyl-1,3-dione
Dehydration
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
catalyst-free reactions.12 In order to evaluate the potential appli-
cations of MCRs in the field of organofluorine chemistry and to
Fluorine-containing compounds have attracted much interest
because of their unique chemical, physical, and biological activi-
ties.1–3 In particular, fluorine-containing heterocycles are now
widely recognized as important organic molecules showing in-
teresting biological activities with potential for applications in the
medicinal and agricultural fields.4,5 The reactions of fluorinated 1,3-
dicarbonyl compounds as fluorine-containing building blocks have
been investigated extensively,6,7 and well established as synthetic
intermediates in heterocyclic chemistry.8 In recent years, the syn-
thesis of fluorinated heterocyclic compounds has drawn much
attention.9
continue our ongoing study on the synthesis of fluorine-containing
heterocyclic compounds via MCRs based on the trifluoromethyl-
1,3-dicarbonyl compounds, a versatile fluorine-containing building
blocks, herein, we wish to report a one-pot, three-component
reaction to 2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-
5(6H)-one derivatives, together with their further chemical
transformations including O-heterocyclics to N-heterocyclics
interconversion and dehydration reactions of
a-hydro-
dihydropyrane moieties to 4-H pyrane derivatives.
2. Results and discussion
Furthermore, the multi-component reactions (MCRs), by virtue
of their convergence, productivity, facile execution, and generally
high yields of products, have attracted much attention from the
vantage point of combinatorial chemistry.10 For example, the syn-
thesis of polyhydroquinoline derivatives was the classical MCRs
involving the three-component coupling of an aldehyde, ethyl
acetoacetate, and ammonia in acetic acid or refluxing alcohol.11
More recently, several alternate and more efficient methods have
been developed for MCRs to polyhydroquinoline derivatives by
using microwave, ionic liquid, TMSCl–NaI, metal triflates, I2, ceric
ammonium nitrate, polymer, organo-catalyst, solvent-free, and
Initially, we carried out the one-pot, three-component reaction
of benzaldehyde 1a and 1,3-cyclohexanedione 2 with 4,4,4-tri-
fluoromethyl-1-(thien-2-yl)-butane-1,3-dione 3 in the presence of
a catalytic amount of triethylamine (10%) in ethanol at room tem-
perature, however, no reaction occurred. Subsequently, the mixture
was heated to reflux, after stirring for 2 h, TLC showed that the
reaction proceeded smoothly and gave the product 4a in 60% yield
(Scheme 1).
Based on the results above, the reaction conditions were opti-
mized to improve the yield by changing bases and solvents. The
effect of a variety of organic bases and the amount on the reaction
efficiency and yield was firstly screened (Table 1). As shown in Table
1, when the reaction was performed in the absence of base, it only
* Corresponding authors.
E-mail addresses: lpsong@shu.edu.cn (L. Song), zhusz@mail.sioc.ac.cn (S. Zhu).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.04.020

S. Song et al. / Tetrahedron 64 (2008) 5728–5735
5729
O
Ar
O
O
O
O
O
S
Et3N, 25%mol
EtOH, Ref.
F3C
ArCHO
OH
CF3
S
O
1(a-j)
4(a-j)
2
3
Ar = C6H5
p-ClC6H4
a
b
c
d
e
f
p-CH3C6H4
p-CH3OC6H4
p-HOC6H4
p-NO2C6H4
m-NO2C6H4
m-PhOC6H4
m-BrC6H4
g
h
i
p-(Me)2NC6H4
j
Scheme 1.
Table 2
afforded product 4a in 10% yield (entry 1, Table 1), however, when
0.25 equiv of Et3N was used, the yield was improved significantly
(entry 3, Table 1). The reaction took much longer reaction time to
give the 4a in 40% yield when pyridine was involved as catalyst
(entry 8, Table 1). Other organic bases such as DABCO, DMAP, and
piperidine catalyzed the reactions giving almost the same results as
the triethylamine catalyzed reaction in terms of reaction time and
yields (entries 5–7, Table 1). Higher amounts of catalyst did not
further improve the yield of 4a (entry 4, Table 1).
Solvent effect was the next considered factor. As shown in Table
1, generally, the reactions gave the better yields in polar protic
solvents such as MeOH or EtOH than that in polar aprotic solvents
(entries 7–11, Table 1), even though the latter reactions were
carried out in prolonged reaction time. Moreover, the reaction in
absolute ethanol under the nitrogen atmosphere gave the same
product yield as that in the commercially available ethanol, in-
dicating that the trace of water in ethanol did not accelerate the
reaction obviously (entries 12 and 13, Table 1).
Reaction results of the one-pot, three-component reaction of aryldehyde 1 and 1,3-
cyclohexanedione 2 with 4,4,4-trifluoro-1-(thien-2-yl)-butane-1,3-dione 3a
Entry
Ar¼
C6H5
Time/h
Product
Yieldb (%)
1
2
3
4
5
6
7
8
2
3
24
8
12
12
2
5
2
10
12
4a
4b
4b
4c
4d
4e
4f
4j
4h
4i
68
85
88
65
36
65
60
60
66
48
47
p-CH3C6H4
p-CH3C6H4
p-CH3OC6H4
p-HOC6H4
p-(Me)2NC6H4
p-ClC6H4
p-NO2C6H4
m-NO2C6H4
m-PhOC6H4
m-BrC6H4
9
10
11
4j
a
Reaction conditions: aryldehyde
1 (1.5 mmol), 1,3-cyclohexanedione 2
(1.5 mmol), 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione
(25% equiv), EtOH (15 mL), refluxing.
2 (1.5 mmol), Et3N
b
Isolated yield.
With the optimal results in hand as shown in Table 1, entry 3, we
investigated the scope and limitation of this one-pot, three-com-
ponent reaction with a variety of aldehydes, and the appropriate 4
were generally obtained in moderate to good yields (Scheme 1).
The reaction results are summarized in Table 2. On one hand, the
aryldehydes bearing either electron-donating or electron-with-
drawing group have not shown the obvious effort on the formation
of the expected products. On the other hand, the substituents lo-
cated at para or meta positions of aryldehydes have not shown the
much effort on the formation of products, too (entries 8 and 9, Table
2). Prolonged reaction time from 2 h to 24 h slightly increased the
yield (entries 2 and 3, Table 2). However, the steric effect of sub-
stituent was noticeable. For example, ortho substituted aryldehydes
such as 2-methoxyl-benzaldehyde or 2-bromo-benzaldehyde gave
no expected product, TLC analysis showed that the starting material
remained. Similarly, steric aromatic hindered aryldehydes such as
1-naphthaldehyde13 or 3,4-dimethoxyl-benzaldehyde, gave no
expected product, too. The above results have shown that the re-
activity of the aryldehyde differs significantly depending on the
steric effect, other than the nature of electronic effect of the sub-
stituents. Other aldehydes, either the furan-2-carbaldehyde or the
aliphatic aldehydes such as acetaldehyde and cinnamic aldehyde
were also invested in the reaction, unfortunately, there was no
expected product obtained. It should be noted that in the case of 4d
(entry 5, Table 2), the yield was lower than that of other arylde-
hydes, even after modification of the reaction conditions like
prolonged reaction time.
The structures of compounds 4 were fully confirmed by 1H NMR,
19F NMR, MS, IR spectroscopies and elemental analysis. For in-
stance, the characteristic features of the 1H NMR in CDCl3 spectra of
Table 1
The effect of a variety of bases and solvents on this one-pot reactiona
Entry
1 (Ar¼)
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
p-NO2C6H4
p-NO2C6H4
Solvent
Base (equiv)
dc
Time/h
Yield of 4ab (%)
4b were the appearances of doublets at
d 4.02 and 3.80 ppm with
1
2
3
4
5
6
7
8
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeOH
DME
2
2
2
2
8
10
60
68
68
60
63
65
40
48
11
15
47
60
60
JH–H¼11.7 Hz for 3-H and 4-H protons, respectively, indicating that
a trans configuration of the vicinal two hydrogen atoms. The
chemical shift of CF3 group in 19F NMR was a singlet peak at
Et3N (0.1)
Et3N (0.25)
Et3N (0.5)
d
ꢀ80.66 ppm (s, 3F), which indicated that the CF3 group was
DABCO (0.25)
DMAP (0.25)
Piperidine (0.25)
Pyridine (0.25)
Et3N (0.25)
Et3N (0.25)
Et3N (0.25)
Et3N (0.25)
Et3N (0.25)
Et3N (0.25)
bonded to a quaternary carbon atom. In most cases, the products 4
2
2
52
2
72
72
24
2
9
Table 3
10
11
12
13
14
One-pot reaction of 1a with 2 and 3 in different amount of NH4OAca
CH2Cl2
CH3CN
EtOH
EtOHd
Entry
NH4OAc (equiv)
Time/h
Yieldsb (%)
Product 4a
Product 5
2
1
2
3
0.25
1
30
10
10
10
65
60
Trace
10
33
55
a
Reaction conditions: aryldehyde
1 (1.5 mmol), 1,3-cyclohexanedione 2
(1.5 mmol), 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-dione
15 mL, refluxing.
3 (1.5 mmol), solvent:
b
a
Isolated yield.
Without base.
Reaction conditions: 1a (1.5 mmol), 2 (1.5 mmol), 3 (1.5 mmol), EtOH (12 mL),
c
refluxing.
d
b
The reaction was carried out in freshly distilled absolute EtOH under nitrogen.
Isolated yield.

5730
S. Song et al. / Tetrahedron 64 (2008) 5728–5735
CHO
O
O
O
O
O
O
O
O
NH4OAc
+
F3C
OH
CF3
OH
CF3
EtOH, Ref.
S
S
S
N
H
O
4a
5a
1a
2
3
NH4OAc (excess)
EtOH, ref., 67%
Scheme 2.
had poor solubility in CDCl3, therefore, most of 1H NMR spectra of
products 4 were recorded in DMSO-d6, however, the characteristic
peaks for 3-H and 4-H in DMSO-d6 somehow revealed one broad
products 4 would be obtained in the presence of catalytic amount
of NH4OAc, whereas the polyhydroquinoline derivatives should be
formed in the presence of stoichiometric amount of NH4OAc. Thus,
we examined the amount of NH4OAc affecting the formation of
products and the yields. The reaction results are listed in Table 3.
As expected, the reaction occurred smoothly under refluxing in
ethanol in the presence of catalytic amount of NH4OAc (0.25 equiv)
and afforded 4a as the major product in 65% yield, along with minor
peak in the range of
d 4.1 ppm.
More recently, ammonium acetate has been used widely as
a base or a catalyst in Hantzsch reactions as well as other re-
actions.14 With this aim in view, we applied ammonium acetate to
the above one-pot reaction. It was hoped that the expected
Figure 1. Crystal structure (a) and packing map (b) of 5a.

S. Song et al. / Tetrahedron 64 (2008) 5728–5735
5731
Table 5
The crystal data of 5a and 8b
Hantzsch product 5a in 10% yield (Scheme 2). The low yield of 5a
was caused by the insufficiency of NH3 source in reaction medium
(entry 1, Table 3). Thus, NH4OAc was increased to stoichiometric
amount, it was noticed that, although the higher amount of NH4OAc
led to the improvement in the yield of Hantzsch product 5a from
10% to 33%, the major product was still 4a (entry 2, Table 3). This
result was in agreement with the previous reported work,15 in
which initial formation of the Hantzsch product appeared low due
to large quantities of the intermediate pyran derivative formed
instead. Furthermore, the pyran derivatives could be converted by
either in situ or a stepwise reaction16 to the corresponding
Hantzsch pyridine derivatives. Inspired by the above works, the
one-pot reaction was carried out in the presence of 30 equiv of
NH4OAc, as expected, the reaction gave the product 5a in 55% yield
exclusively, without the formation of 4a. This result suggested that
the O-atom ring to N-atom ring interconversion could be achieved
by treatment of 4 with an excess of NH4OAc. To verify the sugges-
tion, we carried out the ring to ring interconversion reaction by
treatment of 4a with an excess of NH4OAc in refluxing ethanol
(Scheme 2).
Compounds
5a
681206
21H18F3NO3S
421.42
273(2)
0.71073
Monoclinic
P2(1)/n
8b
CCDC
Empirial formula
fw
Temp (K)
Wavelength (Å)
Cryst syst
Space group
Unit cell dimens
a (Å)
681207
C22H17F3O3S
418.42
C
298(2)
0.71073
Monoclinic
P2(1)/c
8.4560(8)
18.8442(18)
12.0666(12)
90
95.4540(10)
90
1914.1(3)
4
1.462
10.123(3)
16.980(4)
12.138(3)
90
102.915(4)
90
2033.6(9)
4
1.367
b (Å)
c (Å)
a
b
g
(deg)
(deg)
(deg)
Volume (Å3)
Z
Calcd density (Mg/m3)
Absorp coeff (mmꢀ1
F(000)
)
0.221
872
0.206
864
Cryst size (mm)
0.30ꢂ0.20ꢂ0.20
0.30ꢂ0.20ꢂ0.15
q
range for data
2.01–25.05
2.06–25.05
As expected, 5a was obtained in 67% yield, whose structure
was further confirmed by XRD analysis. It was unambiguous to
observe the trans relationship between the vicinal six-membered
ring protons in compound 5a. The molecular structure and
packing map of 5a are shown in Figure 1. Several selected bond
lengths and selected bond angles are listed in Table 4. The crystal
date and refinement details are listed in Table 5. The structure
solution revealed that the proton attached to oxygen O2 of
hydroxyl group formed a intramolecular H-bond with the oxygen
O3 of carbonyl group (D(O3/H2A)¼2.057 Å; :(O2–H2A/O3)¼
143.70ꢁ). In addition, in the crystal, each of the two molecules
were related by two intermolecular H-bonds involving the
protons attached nitrogen N1 and carbon C7 with the oxygen O1
of carbonyl group, respectively, (D(O1/H1A)¼2.032 Å; :(N1–
H1A/O1)¼154.36ꢁ; D(O1/H7A)¼2.510 Å; :(O1/H7A–C7)¼
139.21ꢁ).
collection (deg)
Limiting indices
ꢀ10ꢃhꢃ10, ꢀ22ꢃkꢃ10,
ꢀ14ꢃlꢃ14
ꢀ10ꢃhꢃ12, ꢀ20ꢃkꢃ17,
ꢀ9ꢃlꢃ14
Reflections
9738/3390 [R(int)¼0.0140]
10,462/3586
collected/unique
[R(int)¼0.0319]
Goodness-of-fit on F2
1.056
0.996
Final R indices [I>2
R indices (all data)
Largest diff peak
s
(I)]
R1¼0.0569, wR2¼0.1662
R1¼0.0644, wR2¼0.1740
0.668 and ꢀ0.7043
R1¼0.0442, wR2¼0.0869
R1¼0.0738, wR2¼0.1006
0.319 and ꢀ0.239
and hole (e Åꢀ3
)
O
Ph
O
O
O
O
CHO
O
O
R2
Et3N, 25%
R2
EtOH, Ref.
OH
R1
R1
6(a-d)
7(a-d)
1
2
We also examined the one-pot, three-component reaction with
other 1,3-dicarbonyl compounds such as fluorinated substrates (6a,
6b) or non-fluorinated substrates (6c, 6d), and similar results were
found with these compounds (Scheme 3). The reaction results are
summarized in Table 6. However, with 1,3-diketones yields were
R
1 = CF3, R2 = Me,
2 = OEt,
1 = CH3, R2 = Me,
2 = OEt,
a
b
c
d
R
R
R
Scheme 3.
somewhat lower than the corresponding b-oxo ester (entries 1–4,
Table 6). It is very typical for cyclic CF3-compounds containing
hemi-ketal, himi-aminal or even himi-amidal fragment because of
the strong electron-withdrawing properties of CF3 group.15 How-
ever, it should be noted that in our cases of non-fluorinated sub-
strates (6c, 6d), the similar hemi-ketal fragments were also formed
instead of the formation of 4-H pyran moiety (entries 3 and 4,
Table 6).
Finally, we studied the dehydration of compounds 4 and 7c. In
contrast to the previous works,7b,c in which the
a-hydro-
dihydropyrane moieties resisted to eliminate water to form the
corresponding dehydrated products, compounds 4 and non-fluo-
rinated analogue 7c were smoothly eliminated water to form the
corresponding 4-H pyrane derivatives in the presence of an excess
of TsOH in boiling CHCl3 in good yields (Scheme 4, Table 7). The
structure of compound 8b was further confirmed by XRD analysis.
Table 4
Selected bond lengths (Å) and bond angles (ꢁ) of compounds 5a and 8b
5a
8b
Bond lengths
C(1)–C(2)
C(2)–C(3)
C(1)–C(9)
C(3)–C(8)
C(8)–N(1)
C(9)–O(2)
C(9)–N(1)
C(9)–C(10)
1.554(3)
1.514(3)
1.543(4)
1.362(4)
1.361(3)
1.408(3)
1.429(4)
1.536(4)
C(1)–C(2)
C(2)–C(3)
C(3)–C(4)
C(4)–C(5)
C(5)–O(1)
C(1)–O(1)
C(1)–C(6)
1.316(3)
1.518(3)
1.511(3)
1.334(3)
1.373(3)
1.387(3)
1.498(3)
Table 6
The one-pot reaction of 1 with 2 and 1,3-dicarbonyl compounds 6a
Entry
R1
R2
Time/h
Products
Yieldb (%)
Bond angles
1
2
3
4
CF3
CF3
CH3
CH3
Me
OEt
Me
OEt
5
3
3
3
7a
7b
7c
7d
53
86
62
79
C(9)–C(1)–C(2)
C(3)–C(2)–C(1)
C(8)–C(3)–C(2)
N(1)–C(8)–C(3)
C(8)–N(1)–C(9)
N(1)–C(9)–C(1)
109.6(2)
108.95(19)
120.6(2)
122.3(2)
122.5(2)
108.9(2)
C(2)–C(1)–O(1)
C(1)–C(2)–C(3)
C(4)–C(3)–C(2)
C(5)–C(4)–C(3)
C(5)–O(1)–C(1)
C(4)–C(5)–O(1)
124.8(2)
121.0(2)
109.54(19)
122.7(2)
117.09(18)
122.5(2)
a
Reaction conditions: 1 (1.5 mmol), 2 (1.5 mmol), 6 (1.5 mmol), Et3N (0.25 equiv),
EtOH (12 mL), refluxing.
b
Isolated yield.

5732
S. Song et al. / Tetrahedron 64 (2008) 5728–5735
O
Ar
O
O
Under the same reaction conditions, non-fluorinated substrates
O
Ar
O
TsOH (4 eq.)
afforded the similar himi-ketal moieties. Besides the organic base
catalysts, NH4OAc catalyzed reaction also gave the same reaction
results. However, in the presence of an excess of NH4OAc, the one-
pot reaction directly afforded 2-(trifluoromethyl)-1,2,3,4,7,8-hex-
ahydroquinolin-5(6H)-one derivative 5, which could also be
obtained from 4 by O-atom ring to N-atom ring interconversion
reaction. Meanwhile, the further chemical transformation in-
R2
OH
R2
CHCl3 reflux
O
R1
R1
4a, 4b, 7c
8(a-c)
R1 = CF3, R2 = Thien-2-yl, Ar = C6H5,
a
b
c
R
R
1 = CF3, R2 = Thien-2-yl, Ar = p-MeC6H4,
1 = CH3, R2 = CH3,
Ar = C6H5,
cluding dehydration of a-hydrodihydropyrane derivatives 4 and 7c
Scheme 4.
with p-TsOH in refluxing CHCl3 proceeded smoothly and gave the
corresponding fluorinated and non-fluorinated products 8,
respectively.
Table 7
Dehydration of a
-hydrodihydropyrane derivativesa
Entry
Ar
R1
R2
Time/h
Product
Yield/%b
4. Experimental section
4.1. General
1
2
3
C6H5
p-CH3C6H4
C6H5
CF3
CF3
CH3
Thien-2-yl
Thien-2-yl
CH3
12
12
4
8a
8b
8c
67
83
73
a
Reaction conditions: 4a,4b,7c (0.5 mmol), p-TsOH (2.0 mmol, 4 equiv), solvent:
Melting points were measured with digital melting point ap-
paratus (WRS-1B, Shanghai precision & scientific instrument Co.,
Ltd.) and were uncorrected .1H and 19F NMR spectra were recorded
in DMSO-d6 (unless mentioned in text) on Bruker AM-300 or AM-
500 instruments with Me4Si and CFCl3 (with upfield negative) as
the internal and external standards, respectively. IR spectra were
obtained with a Nicolet AV-360 spectrophotometer. Lower resolu-
tion mass spectrum were determined with Finnigan GC–MS 4021
using the electron impact ionization technique (70 eV). High res-
olution mass spectra (HRMS) were run on Ionspec 4.7 Tesla FTMS
using MALDI/DHB. Elemental analyses were performed in this
Institute.
CHCl3 (15 mL), refluxing.
b
Isolated yields.
The crystal structure is shown in Figure 2. The selected bond
lengths and selected bond angles are listed in Table 4.
3. Conclusions
In conclusion, we have developed a one-pot reaction for the
synthesis of 2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-
5(6H)-one derivatives 4 from easily available starting materials.
Figure 2. Crystal structure (a) and packing map (b) of 8b.

S. Song et al. / Tetrahedron 64 (2008) 5728–5735
5733
4.2. General procedure for the preparation of 4-aryl-2-
hydroxy-3-(thien-2-oyl)-2-(trifluoromethyl)-3,4,7,8-
tetrahydro-2H-chromen-5(6H)-one (4a–4j)
2H), 2.73–2.81 (s, 6H), 4.01–4.09 (m, 2H), 6.42–6.45 (m, 2H), 6.88–
6.90 (m, 3H), 7.51–7.53 (m, 1H), 7.85–7.88 (m, 1H), 8.62–8.66 (m,
1H); 19F NMR (DMSO-d6, 282 MHz):
d
ꢀ80.64 (s, 3F); IR (KBr) nmax
:
3432, 3090, 2961, 2792, 1662, 1609, 1520, 1452, 1418, 1377, 1358,
To a mixture of aryldehyde 1 (1.5 mmol), 1,3-cyclohexanaedione
2 (168 mg, 1.5 mmol), and 4,4,4-trifluoro-1-(thien-2-yl)butane-1,3-
dione 3 (333 mg, 1.5 mmol) in 12 mL EtOH was added 0.3 mmol of
Et3N as catalyst under stirring at room temperature. The mixture
was refluxed and continuously stirred for specified hour (moni-
tored by TLC). After cooling, the resulting solid was filtered, washed
with 10–15 mL of cold EtOH and air-dried to afford the crude
product. The pure product was obtained by recrystallization from
ethanol.
1071, 820, 745 cmꢀ1; MS (ESI) m/z: [(MþH)þ, 466.2], [(Mþ2H)þ,
467.3]; HRMS for
466.1294.
C
23H23NO4F3Sþ1 Calcd: 466.1300; Found:
4.2.6. 4-(4-Chlorophenyl)-2-hydroxy-3-(thien-2-oyl)-2-
(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4f)
White solid; mp 224–225 ꢁC; 1H NMR (DMSO-d6, 300 MHz):
d
1.83–2.05 (m, 2H), 2.15–2.25 (m. 2H), 2.37–2.61 (m, 2H), 4.10–4.14
(m, 2H), 7.03–7.24 (m, 5H), 7.50–7.60 (m, 1H), 7.89–7.92 (m, 1H),
8.78–8.82 (m, 1H); 19F NMR (DMSO-d6, 282 MHz):
d
ꢀ80.58 (s, 3F);
4.2.1. 2-Hydroxy-4-phenyl-3-(thien-2-oyl)-2-(trifluoromethyl)-
3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4a)
IR (KBr) nmax: 3444, 1657, 1607, 1519, 1493, 1417, 1374, 1073, 810,
727 cmꢀ1; MS (ESI) m/z: [(MþH)þ, 459.0/457.0]; Anal. Calcd for
White solid; mp 222–223 ꢁC; 1H NMR (DMSO-d6, 300 MHz):
C21H16ClF3O4S: C, 55.21; H, 3.53. Found: C, 54.88; H, 3.58.
d
1.91–1.94 (m, 2H), 2.15–2.19 (m, 2H), 2.60–2.63 (m, 2H), 4.06 (s,
1H), 4.13 (s, 1H), 6.93–7.25 (m, 6H), 7.45–7.48 (m, 1H), 7.83–7.88 (m,
1H), 8.74–8.77 (m, 1H); 19F NMR (DMSO-d6, 282 MHz):
4.2.7. 2-Hydroxy-4-(4-nitrophenyl)-3-(thien-2-oyl)-2-
d
ꢀ80.66 (s,
(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4g)
3F); IR (KBr) nmax: 3431, 3100, 2789, 1702, 1659, 1609, 1520, 1496,
1457, 1418, 1360, 1077, 729 cmꢀ1; MS (70 eV, EI) m/z (%): 422 (Mþ,
3.13), 311 [(MꢀC5H3OS)þ, 15.00], 222 (C8H5F3O2Sþ, 25.06), 199
(C13H11Oþ2 , 100), 69 (CF3þ, 31.34); Anal. Calcd for C21H17F3O4S: C,
59.71; H, 4.06. Found: C, 59.57; H, 3.93.
White solid; mp 230–231 ꢁC; 1H NMR (DMSO-d6, 300 MHz):
d
1.96–1.98 (m, 2H), 2.18–2.25 (m, 2H), 2.46–2.57 (m, 2H), 4.25–4.27
(m, 2H), 7.02 (s, 1H), 7.43 (d, J¼8.6 Hz, 2H), 7.64–7.66 (m, 1H), 7.90–
7.94 (m, 1H), 7.95 (d, J¼8.6 Hz, 2H), 8.98–9.00 (m, 1H); 19F NMR
(DMSO-d6, 282 MHz):
d
ꢀ80.92 (s, 3F); IR (KBr) nmax: 3430, 3078,
2792, 1655,1606,1520, 1458,1416, 1074, 806, 760 cmꢀ1; MS (ESI) m/
z: [(MþH)þ, 468.0], [(Mþ2H)þ, 469.0], [(MþHþH2O)þ, 486.7]; Anal.
Calcd for C21H16F3NO6S: C, 53.96; H, 3.45; N, 3.00. Found: C, 53.91;
H, 3.71; N, 2.70.
4.2.2. 2-Hydroxy-3-(thien-2-oyl)-4-p-tolyl-2-(trifluoromethyl)-
3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4b)
White solid; mp 216–218 ꢁC; 1H NMR (CDCl3, 300 MHz):
d 2.02–
2.10 (m, 2H), 2.16 (s, 3H), 2.28–2.38 (m, 2H), 2.58–2.66(m, 2H), 3.80
(d, J¼11.7 Hz, 1H), 4.03 (d, J¼11.7 Hz, 1H), 6.33 (br s, 1H), 6.87–7.01
4.2.8. 2-Hydroxy-4-(3-nitrophenyl)-3-(thien-2-oyl)-2-
(m, 6H), 7.64 (m, 1H); 19F NMR (DMSO-d6, 282 MHz):
d
ꢀ83.43 (s,
(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4h)
CF3); IR (KBr) nmax: 3305, 3090, 3032, 2968, 2878, 1662, 1606, 1519,
1458, 1419, 1377, 1073, 816, 752 cmꢀ1; MS (70 eV, EI) m/z (%): 436
(Mþ, 1.65), 325 [(MꢀC5H3OS)þ, 10.48], 222 (C8H5F3O2Sþ, 9.43), 199
(C13H11Oþ2 , 100), 69 (CF3þ, 13.12); Anal. Calcd for C22H19F3O4S: C,
60.54; H, 4.39. Found: C, 60.38; H, 4.24.
Light yellow solid; mp 236–237 ꢁC; 1H NMR (DMSO-d6,
300 MHz):
d 1.97–1.98 (m, 2H), 2.22–2.28 (m, 2H), 2.44–2.66 (m,
2H), 4.28 (br s, 2H), 7.00 (s, 1H), 7.36–7.39 (m, 1H), 7.57–7.68 (m,
2H), 7.85–8.00 (m, 3H), 8.90–8.95 (m, 1H); 19F NMR (DMSO-d6,
282 MHz):
d
ꢀ80.54 (s, 3F); IR (KBr) nmax: 3298, 3097, 2970, 2895,
2785, 2584, 2005, 1944, 1885, 1840, 1763, 1660, 1609, 1500, 1481,
1457, 1417, 1077, 750, 690, 711 cmꢀ1; MS (70 eV, EI) m/z (%): 467
(Mþ, 5.83), 356 [(MꢀC5H3OS)þ, 17.24], 245 [(MꢀC8H5F3O2S)þ,
32.15], 228 (C13H10NOþ3 ,100), 222 (C8H5F3O2Sþ, 95.90), 199
(C13H11Oþ2 , 45.17), 153 (C7H5O2Sþ, 94.29), 111 (C5H3OSþ,78.45), 69
(CFþ3 ,96.79); Anal. Calcd for C21H16F3NO6S: C, 53.96; H, 3.45; N, 3.00.
Found: C, 53.89; H, 3.58; N, 2.88.
4.2.3. 2-Hydroxy-4-(4-methoxyphenyl)-3-(thien-2-oyl)-2-
(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4c)
White solid; mp 226–227 ꢁC; 1H NMR (DMSO-d6, 300 MHz):
d
1.91–1.95 (m, 2H), 2.17–2.21 (m, 2H), 2.48–2.59 (m, 2H), 3.32 (s,
1H), 3.58 (s, 3H), 4.08–4.11 (m, 2H), 6.61–6.65 (m, 2H), 6.96–7.02
(m, 3H), 7.50–7.58 (m, 1H), 7.86–7.88 (m, 1H), 8.65–8.75 (m, 1H); 19
NMR (DMSO-d6, 282 MHz):
F
d
ꢀ80.65 (s, 3F); IR (KBr) nmax: 3431,
3090, 2967, 2835, 1660, 1605, 1513, 1459, 1418, 1375, 1255, 1072,
834 cmꢀ1; MS (ESI) m/z: [(MþH)þ, 453.3], [(MþNa)þ, 475.2],
[(MþK)þ, 491.2]; Anal. Calcd for C22H19F3O5S: C, 58.40; H, 4.23.
Found: C, 58.39; H, 4.03.
4.2.9. 2-Hydroxy-4-(3-phenoxyphenyl)-3-(thien-2-oyl)-2-
(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4i)
Light yellow solid; mp 196–197 ꢁC; 1H NMR (DMSO-d6,
300 MHz): d 1.90–1.98 (m, 2H), 2.21–2.24 (m, 2H), 2.51 (s, 2H), 4.11
(br s, 2H), 6.59–6.63 (m, 3H), 6.67 (s, 1H), 6.75–6.79 (m, 1H), 7.04–
7.15 (m, 3H), 7.29 (m, 2H), 7.58 (m, 1H), 7.98 (m, 1H), 8.81 (m, 1H);
4.2.4. 2-Hydroxy-4-(4-hydroxyphenyl)-3-(thien-2-oyl)-2-
(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4d)
White solid; mp 203–204 ꢁC; 1H NMR (DMSO-d6, 300 MHz):
19F NMR (DMSO-d6, 282 MHz):
d
ꢀ81.13 (s, 3F); IR (KBr) nmax: 3310,
3040, 2782, 2581, 1660, 1600, 1518, 1480, 1445, 1416, 1357, 1200,
d
1.88–1.92 (m, 2H), 2.15–2.18 (m, 2H), 2.34–2.70 (m, 2H), 3.98–4.07
1070, 750, 727, 708 cmꢀ1
;
MS (ESI) m/z: [(MþH)þ, 515.2],
(m, 2H), 6.43–6.46 (m, 2H), 6.86–7.03 (m, 3H), 7.49–7.56 (m, 1H),
[(Mþ2H)þ, 516.3]; Anal. Calcd for C27H21F3O5S: C, 63.03; H, 4.11.
7.87–7.89 (m, 1H), 8.65–8.70 (m, 1H), 8.95–9.01 (m, 1H); 19F NMR
Found: C, 62.51; H, 4.36.
(DMSO-d6, 282 MHz):
d
ꢀ80.73 (s, 3F); IR (KBr) nmax: 3510, 3430,
3096, 2981, 2768,1664,1655,1605,1517, 1448,1419, 1185, 1072, 805,
745 cmꢀ1; MS (ESI) m/z: [(MþH)þ, 439.3], [(Mþ2H)þ, 440.2],
[(MþNa)þ, 461.0], [(MþK)þ, 477.0], [(MþKþH2O)þ, 493.0]; HRMS
for C21H17 F3O5Sþ1 Calcd: 438.0749; Found: 438.0762.
4.2.10. 4-(3-Bromophenyl)-2-hydroxy-3-(thien-2-oyl)-2-
(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4j)
Light yellow solid; mp 236–237 ꢁC; 1H NMR (DMSO-d6,
300 MHz):
2H), 4.13 (br s, 2H), 7.03–7.04 (m, 2H), 7.12–7.18 (m, 2H), 7.27–7.30
(m, 1H), 7.61–7.64 (m, 1H), 7.90–7.92 (m, 1H), 8.80–8.85 (m, 1H); 19
NMR (DMSO-d6, 282 MHz):
d 1.95–1.98 (m, 2H), 2.20–2.23 (m, 2H), 2.50–2.56 (m,
4.2.5. 4-(4-(Dimethylamino)phenyl)-2-hydroxy-3-(thien-2-oyl)-2-
(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (4e)
Light yellow solid; mp 205–207 ꢁC; 1H NMR (DMSO-d6,
F
d
ꢀ80.57 (s, 3F); IR (KBr) nmax: 3436,
3079, 2964, 2891, 1658, 1608, 1518, 1476, 1457, 1416, 1362, 1189, 806,
300 MHz):
d
1.90–1.92 (m, 2H), 2.14–2.18 (m, 2H), 2.44–2.53 (m,
726 cmꢀ1; MS (70 eV, EI) m/z (%): 500 (Mþ, 1.58), 391/389

5734
S. Song et al. / Tetrahedron 64 (2008) 5728–5735
[(MꢀC5H3OS)þ, 4.63/5.10], 222 (C8H5F3O2Sþ, 16.77), 199 (C13H11Oþ2 ,
100), 69 (CFþ3 , 18.50); Anal. Calcd for C21H16BrF3O4S: C, 50.31; H,
3.22. Found: C, 50.01; H, 3.35.
69 (CFþ3 , 66.20); Anal. Calcd for C19H19O5F3: C, 59.38; H, 4.95. Found:
C, 59.29; H, 4.78.
4.4.3. 3-Acetyl-2-hydroxy-2-methyl-4-phenyl-3,4,7,8-tetrahydro-
2H-chromen-5(6H)-one (7c)
4.3. Preparation of 2-hydroxy-4-phenyl-3-(thien-2-oyl)-2-
(trifluoromethyl)-1,2,3,4,7,8-hexahydroquinolin-5(6H)-one 5
White solid; mp 178–180 ꢁC; 1H NMR (CDCl3, 500 MHz):
d 1.50
(s, 3H), 1.80 (s, 3H), 1.88 (t, J¼5.5 Hz, 2H), 2.24–2.34 (m, 2H), 2.44–
2.51 (m, 2H), 3.14 (d, J¼8.0 Hz, 1H), 3.91 (d, J¼8.0 Hz, 1H), 7.11–7.25
(m, 5H); IR (KBr) nmax: 3202, 3029, 2963, 2925, 2880, 1719, 1631,
1585, 1492, 1453, 1421, 1380, 1071, 727, 702 cmꢀ1; MS (70 eV, EI)
m/z (%): 300 (Mþ, 1.52), 257 [(MꢀCH3CO)þ, 18.58], 215
[(MꢀCH3ꢀC4H6O)þ, 46.61], 199 (C13H11O2þ, 79.54), 43 (CH3COþ,
100),116 (C5H8Oþ3 ,10.39); Anal. Calcd for C18H20O4: C, 71.98; H, 6.71.
Found: C, 71.95; H, 6.76.
Method A: To a mixture of benzaldehyde 1a (159 mg, 1.5 mmol),
1,3-cyclohexanedione 2 (168 mg, 1.5 mmol), and 4,4,4-trifluoro-1-
(thien-2-yl)butane-1,3-dione 3 (333 mg, 1.5 mmol) in 10 mL EtOH
was added 30 equiv of NH4OAc under stirring at room temperature.
The mixture was refluxed and continually stirred for specified hour
(monitored by TLC). After cooling, the mixture was poured into
20 mL water, and extracted with CH2Cl2 three times (3ꢂ15 mL). The
combined organic layer was dried with Na2SO4 overnight. The
solvent was removed by rotavapor and the residue was purified by
column chromatography on silica gel using petroleum/ethyl
acetate¼2:1(v/v) as eluent to afford pure product 5.
4.4.4. Ethyl 2-hydroxy-2-methyl-5-oxo-4-phenyl-3,4,5,6,7,8-
hexahydro-2H-chromene-3-carboxylate (7d)
White solid; mp 142–144 ꢁC; 1H NMR (CDCl3, 500 MHz):
d 1.07
(t, J¼7.0 Hz, 3H), 1.52 (s, 3H), 1.99 (s, 2H), 2.59–2.63 (m, 4H), 2.97 (d,
J¼9.5 Hz,1H), 4.05 (q, J¼7.0 Hz, 2H), 4.09 (d, J¼9.5 Hz,1H), 7.12–7.18
(m, 3H), 7.21–7.27 (m, 2H); IR (KBr) nmax: 3318, 3031, 2941, 2998,
Method B: Preparation of 5 from 4. The procedure is same as
the above except the 2-hydroxy-4-phenyl-3-(thien-2-oyl)-2-
(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one
4a
2871, 1735, 1642, 1612, 1491, 1453, 1422, 1373, 1071, 728, 699 cmꢀ1
;
(422 mg,1 mmol) and 30 equiv of NH4OAc were engaged as starting
materials.
MS (70 eV, EI) m/z (%): 330 (Mþ, 5.50), 287 [(MꢀEtOþ2H)þ, 18.10],
241 [(MꢀEtOCOꢀOH)þ, 100], 199 (C13H11O2þ, 76.64), 129 (C6H9Oþ3 ,
16.66), 43 (CH3COþ, 94.78); Anal. Calcd for C19H22O5: C, 69.07; H,
6.71. Found: C, 69.10; H, 6.79.
4.3.1. 2-Hydroxy-4-phenyl-3-(thien-2-oyl)-2-(trifluoromethyl)-
1,2,3,4,7,8-hexahydroquinolin-5(6H)-one (5a)
Yellow solid; 231–232 ꢁC; 1H NMR (CDCl3, 500 MHz):
d 2.18–
4.5. General procedure for dehydration reaction
2.22 (m, 2H), 2.28–2.41 (m, 2H), 2.52–2.55 (m, 2H), 3.83 (d,
J¼11.5 Hz, 1H), 4.19 (d, J¼11.5 Hz,1H), 5.10 (s, 1H), 6.04 (s, 1H), 6.84–
6.86 (m, 1H), 6.98–7.00 (m, 2H), 7.06–7.11 (m, 4H), 7.60–7.62 (m,
The solution of 0.5 mmol of 4 or 7 and 4 equiv of p-TsOH in 15 mL
of CHCl3 was refluxed for several hours until complete of reaction
(monitored by TLC). The solvent was removed by rotavapor and the
residue was purified by column chromatography using petroleum/
ethyl acetate¼2:1(v/v) as eluent to afford pure product 8.
1H); 19F NMR (CDCl3, 470 MHz):
d
ꢀ82.24 (s, 3F); IR (KBr) nmax
:
3269, 3109, 3044, 2958, 2928, 2890, 1634, 1599, 1533, 1455, 1411,
1034, 1192, 734, 705 cmꢀ1; MS (ESI) m/z: [(MþH)þ, 422], [(Mþ2H)þ,
423]; Anal. Calcd for C21H18F3NO3S: C, 59.85; H, 4.31; N, 3.32.
Found: C, 60.12; H, 4.42; N, 3.20.
4.5.1. 4-Phenyl-3-(thien-2-oyl)-2-(trifluoromethyl)-7,8-dihydro-
4H-chromen-5(6H)-one (8a)
4.4. General procedure for preparation of 7a–7d
Light red solid; mp 134–136 ꢁC; 1H NMR (CDCl3, 500 MHz):
d
2.02–2.17 (m, 2H), 2.39–2.45 (m, 2H), 2.65–2.78 (m, 2H), 4.74 (s,
The procedure is same as the preparation of 4 except that after
cooling, the solvent was removed by rotavapor, and the residue was
purified by column chromatography on silica gel using petroleum/
ethyl acetate¼1.5:1(v/v) as eluent to afford the pure products 7.
1H), 6.91 (dd, J1¼4.8 Hz, J2¼5.0 Hz, 1H), 7.10 (d, J¼3.5 Hz, 1H), 7.12–
7.17 (m, 3H), 7.19–7.23 (m, 2H), 7.61 (dd, J1¼4.8 Hz, J2¼5.0 Hz, 1H);
19F NMR (CDCl3, 470 MHz):
d
ꢀ66.98 (s, 3F); IR (KBr) nmax: 3438,
3088, 2961, 2921, 2867,1699,1640,1518,1489,1454,1376,1152, 725,
743, 700 cmꢀ1; MS (70 eV, EI) m/z (%): 404 (Mþ, 69.73), 335
[(MꢀCF3)þ, 17.99], 111 (C5H3OSþ, 100); Anal. Calcd for C21H15F3O3S:
C, 62.37; H, 3.74. Found: C, 62.39; H, 3.86.
4.4.1. 3-Acetyl-2-hydroxy-4-phenyl-2-(trifluoromethyl)-3,4,7,8-
tetrahydro-2H-chromen-5(6H)-one (7a)
White solid; mp 203–204 ꢁC; 1H NMR (CDCl3, 500 MHz):
d 1.72
(s, 3H), 1.97–2.08 (m, 2H), 2.22–2.38 (m, 2H), 2.51–2.66 (m, 2H),
3.28 (d, J¼11.5 Hz, 1H), 3.83 (d, J¼11.5 Hz, 1H), 5.73 (s, 1H), 7.12 (d,
J¼7.0 Hz, 2H), 7.24 (t, J¼7.0 Hz, 1H), 7.31 (t, J¼2.0 Hz, 2H); 19F NMR
4.5.2. 3-(Thien-2-oyl)-4-p-tolyl-2-(trifluoromethyl)-7,8-dihydro-
4H-chromen-5(6H)-one (8b)
White solid; mp 145–147 ꢁC; 1H NMR (CDCl3, 500 MHz):
d 2.00–
(CDCl3, 470 MHz):
d
ꢀ83.52 (s, 3F); IR (KBr) nmax: 3447, 3051, 2950,
2.15 (m, 2H), 2.24 (s, 3H), 2.34–2.44 (m, 2H), 2.63–2.78 (m, 2H), 4.69
(s, 1H), 6.94 (dd, J1¼4.8 Hz, J2¼5.0 Hz, 1H), 7.00–7.06 (m, 4H), 7.17
(d, J¼3.5 Hz, 1H), 7.63 (dd, J1¼4.8 Hz, J2¼5.0 Hz, 1H); 19F NMR
2920, 2870, 1726, 1680, 1495, 1456, 1423, 1360, 1191, 714 cmꢀ1; MS
(70 eV, EI) m/z (%): 354 (Mþ, 3.09), 311 [(MꢀCH3CO)þ, 95.65], 199
(C13H11Oþ2 , 198.25), 69 (CFþ3 , 32.16), 43 (CH3COþ, 100); Anal. Calcd
for C18H17F3O4: C, 61.02; H, 4.84. Found: C, 61.02; H, 4.93.
(CDCl3, 470 MHz):
d
ꢀ66.99 (s, 3F); IR (KBr) nmax: 3439, 3090, 2964,
2923, 2867, 1697, 1641, 1515, 1453, 1412, 1372, 1152, 818 cmꢀ1; MS
(70 eV, EI) m/z (%): 418 (Mþ, 60.18), 403 [(MꢀCH3)þ, 47.37], 307
[(MꢀC5H3OS)þ, 22.71], 111 (C5H3OSþ, 100); Anal. Calcd for
4.4.2. Ethyl 2-hydroxy-5-oxo-4-phenyl-2-(trifluoromethyl)-
3,4,5,6,7,8-hexahydro-2H-chromene-3-carboxylate (7b)
C22H17F3O3S: C; 63.15; H, 4.10. Found: C, 62.92; H, 4.09.
White solid; mp 220–221 ꢁC; 1H NMR (CDCl3, 300 MHz):
d 1.00
(t, J¼7.2 Hz, 3H), 1.99–2.09 (m. 2H), 2.23–2.39 (m, 2H), 2.53–2.66
(m, 2H), 2.98 (d, J¼11.7 Hz, 1H), 3.94 (d, J¼11.7 Hz, 1H), 4.04 (q,
J¼7.2 Hz, 2H), 5.57 (s, 1H), 7.08–7.26 (m, 5H); 19F NMR (CDCl3,
4.5.3. 3-Acetyl-2-methyl-4-phenyl-7,8-dihydro-4H-chromen-
5(6H)-one (8c)
Yellow solid; mp 134–136 ꢁC; 1H NMR (CDCl3, 500 MHz):
d 1.84–
282 MHz):
d
ꢀ84.19 (s, 3F); IR (KBr) nmax: 3465, 3050, 2985, 2774,
1.93 (m, 1H), 1.96–2.04 (m, 1H), 2.12 (s, 3H), 2.27–2.41 (m, 5H),
2.45–2.58 (m, 2H), 4.80 (s, 1H), 7.14–7.18 (m, 1H), 7.23–7.30 (m, 4H);
IR (KBr) nmax: 3442, 3051, 3029, 2972, 2943, 1683, 1662, 1586, 1492,
1455, 1424, 714, 699 cmꢀ1; MS (70 eV, EI) m/z (%): 282 (Mþ, 93.03),
2585, 1741, 1610, 1373, 1354, 1238, 1193, 1162, 1018, 704, 619 cmꢀ1
;
MS (70 eV, EI) m/z (%): 384 (Mþ, 3.46), 311 [(MꢀCO2Et)þ, 47.32], 241
[(Mꢀ1ꢀCF3ꢀCO2Et)þ, 100], 199 [(Mꢀ1ꢀCF3COCH2CO2Et)þ, 33.20],

S. Song et al. / Tetrahedron 64 (2008) 5728–5735
5735
267 [(MꢀCH3)þ, 8.19], 239 [(MꢀCH3CO)þ, 18.32], 205 [(MꢀC6H5)þ,
100], 43 (CH3COþ, 84.85); Anal. Calcd for C18H18O3: C, 76.57; H, 6.43.
Found: C, 76.67; H, 6.46.
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tometer using graphite monochromatized Mo
Ka radiation
(l
¼0.71073 Å). The structures were solved by direct methods and
expanded using Fourier techniques. The non-hydrogen atoms were
refined anisotropically, hydrogen atoms were included but not re-
fined. The final cycle of full matrix least-squares refinement was
based on F2. All calculations were performed using SHELEX-97 and
SHELXL-97 programs.
CCDC 681206, 681207 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ,
UK; fax: þ44 1223 336033.
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therein.
The authors thank the National Natural Science Foundation of
China (NNSFC) (No.20772080), the Foundation of Education Com-
mission of Shanghai Municipality (No. J50102) and the Innovation
Fund of Shanghai University for financial support.
13. Mosse, S.; Alexakis, A. Org. Lett. 2006, 8, 3577–3580.
References and notes
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