Synthesis of dihydrofurans containing trifluoromethyl ketone and heterocycles by radical cyclization of fluorinated 1,3-dicarbonyl compounds with 2-thienyl and 2-furyl substituted alkenes

Article abstract of DOI:10.1016/j.tet.2011.08.098

Manganese(III) acetate based radical cyclization of various fluorinated 1,3-dicarbonyl compounds with 2-thienyl and 2-furyl substituted alkenes produced 3-trifluoroacetyl and 2-trifluoromethyl-dihydrofurans in good yields. The radical cyclizations of 2-methyl-5-[(E)-2-phenylvinyl]furan 2b and 2-[(E)-2-phenylvinyl]thiophene 2c led to the formations of 5-(5-methyl-2-furyl)- 4,5-dihydrofuran and 5-(2-thienyl)-4,5-dihydrofuran, respectively. In the reactions of 1,3-dicarbonyls with alkenes, 2-thienyl substituted alkenes formed 4,5-dihydrofurans in higher yields than 2-furyl substituted alkenes.

Full text of DOI:10.1016/j.tet.2011.08.098

Tetrahedron 67 (2011) 8255e8263
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Tetrahedron
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Synthesis of dihydrofurans containing trifluoromethyl ketone and heterocycles by
radical cyclization of fluorinated 1,3-dicarbonyl compounds with 2-thienyl and
2-furyl substituted alkenes
*
Mehmet Yılmaz
Department of Chemistry, Faculty of Arts and Sciences, Kocaeli University, 41380 Umuttepe, Kocaeli, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 March 2011
Received in revised form 11 August 2011
Accepted 31 August 2011
Available online 7 September 2011
Manganese(III) acetate based radical cyclization of various fluorinated 1,3-dicarbonyl compounds with
2-thienyl and 2-furyl substituted alkenes produced 3-trifluoroacetyl and 2-trifluoromethyl-dihydrofur-
ans in good yields. The radical cyclizations of 2-methyl-5-[(E)-2-phenylvinyl]furan 2b and 2-[(E)-2-
phenylvinyl]thiophene 2c led to the formations of 5-(5-methyl-2-furyl)-4,5-dihydrofuran and 5-(2-
thienyl)-4,5-dihydrofuran, respectively. In the reactions of 1,3-dicarbonyls with alkenes, 2-thienyl
substituted alkenes formed 4,5-dihydrofurans in higher yields than 2-furyl substituted alkenes.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Manganese(III) acetate
Radical cyclization
Fluorinated 1,3-dicarbonyl
Trifluoromethyl ketone
4,5-Dihydrofuran
1. Introduction
Recently, we have prepared 2,3-dihydro-4H-furo[3,2-c]chro-
men-4-ones and 2,3-dihydronaphtho[2,3-b]furan-4,9-diones by
Fluorinated organic compounds are very important due to their
unique chemical and biological properties. Thus, these compounds
have received considerable attention in the medicinal and agri-
cultural chemistry.1 Many trifluoromethyl ketones have been found
to be enzyme inhibitor,2 antimicrobial activity,3 and some tri-
fluoromethyl ketones have been demonstrated as cytotoxic agents
against human tumor cell.4
Dihydrofurans are a significant class of compounds since they
showawide range ofbiologicalactivities andform the basicstructure
of many natural compounds.5 Our research group has been studying
the synthesis of dihydrofuran derivatives by the radical cyclization of
various 1,3-dicarbonyl compounds and 3-oxopropanenitriles with
alkenes, alkynes, unsaturated amides, and dienes.6 One possible
approach for the synthesis of trifluoromethyl ketone containing
dihydrofurans would be the cyclization of a suitable fluorinated
1,3-dicarbonyl compound with an unsaturated system mediated by
transitionmetalsalts (Mnþ3, Ceþ4, Agþ etc.). Amongthesemetalsalts,
manganese(III) acetate,7 and cerium(IV) ammonium nitrate7h,8 are
widely used as radical oxidants in organic synthesis for the con-
struction of carbonecarbon bonds.
the radical cyclization of 4-hydroxycoumarin and 2-hydroxy-1,4-
naphtoquinone, respectively.6e Moreover, we described the syn-
thesis of 3-trifluoroacetyl-4,5-dihydrofurans and 3-[dihydrofurans-
2(3H)-ylidene]-1,1,1-trifluoroacetones by the treatments of tri-
fluoromethyl-1,3-dicarbonyl compounds with alkenes.6i In this
paper, it is reported that radical cyclization of several available tri,
and hepta fluorinated 1,3-dicarbonyl compounds 1aef with
2-thienyl and 2-furyl substituted alkenes 2aeh using man-
ganese(III) acetate to afford trifluoromethyl ketone containing
dihydrofurans and 2-trifluoromethyl-dihydrofurans.
2. Results and discussions
The mechanism proposed for the formation of dihydrofurans is
explained in Scheme 1. According to this mechanism, the in-
teraction of enol form A of the 1,3-dicarbonyl 1aef with man-
ganese(III) acetate produces Mn(III)eenolate complex B. While an
electron from alkene is added to Mn(III)eenolate complex B, Mn3þ
is reduced to Mn2þ and a radical carbon intermediate product C is
formed via pathway i. The structure C is oxidized to carbocation D
with Mn(OAc)3. Cyclization of the carbocation
D
afford
3-trifluoroacetyl-dihydrofuran E. Similarly, dihydrofuran G can be
produced through the cyclization of intermediate carbocation F
formed by the addition of an electron from alkene to the complex B
* Tel.: þ90 262 3032058; fax: þ90 262 3032003; e-mail address: mehme-
t.yilmaz@kocaeli.edu.tr.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.098

8256
M. Yılmaz / Tetrahedron 67 (2011) 8255e8263
Mn+3
O
Mn+2
O
O
O
O
Ph
X
R
OH
O
O
R
CF3
ii
R
CF3
Mn(OAc)3
B
CF3
R
R
CF3
O
A
ii
X
Ph
Ph
X: O, S
X
i
F
G
i
O
Mn+2
O
Mn+2
O
CF3
1a-f
X
O
O
O
R
R
CF3
Ph
R
CF3
Ph
R: 2-thienyl, 2-furyl
phenyl, 2-naphtyl
methyl
CF3
Ph
O
Mn+3
Mn+2
X
X
C
D
E
Scheme 1. Mechanism for the formation of dihydrofurans.
by pathway ii. Compounds G and E were differentiated by using
HSQC and HMBC spectra. The H5 protons on each of these com-
pounds are observed at lower field than that of H4 protons in the 1H
NMR spectra because the H5 protons are adjacent to the ether
oxygen, thus the carbon atoms attached to these protons were
easily determined by HSQC. Moreover, the HMBC spectra show the
C4 carbon correlates with the ortho-protons of the phenyl group,
thus the Ph group must be attached to the C4 carbon. According to
these results, the isolated compound is E, produced by the cycli-
zation of carbocation D formed by the pathway i.
As seen in Table 1, whilst the reactions of 4,4,4-trifluoro-1-(2-
thienyl)butane-1,3-dione 1a with 2-[(E)-2-Phenylvinyl]furan 2a
yielded no product, the reaction of 1a with 2-methyl-5-[(E)-2-
phenylvinyl]furan 2b and 2-[(E)-2-phenylvinyl]thiophene 2c yiel-
ded 3-trifluoroacetyl-dihydrofurans 3a and 3b in low yields, re-
spectively. Compounds 3a (dr¼88:12) and 3b (dr¼85:15) were
isolated as diastereomeric mixtures and the ratio was determined
by 1H NMR.
higher activity in these radical cyclizations in comparison with the
alkenes containing furyl and phenyl group. Additionally, the radical
cyclizations of 2f with the other fluorinated 1,3-dicarbonyl com-
pounds gave dihydrofurans in very good yields. Similarly, while the
reactions of 2-[1-(4-methylphenyl)vinyl]thiophene 2g produced
dihydrofurans 3oeq in good yields, the best results were obtained
from the reactions of 2-[1-(4-fluorophenyl)vinyl]thiophene (2h)
with 1,3-dicarbonyls (Table 3).
In conclusion, the radical cyclizations of various fluorinated 1,3-
dicarbonyl compounds with 2-thienyl and 2-furyl substituted al-
kenes mediated by Mn(OAc)3 were performed in this study com-
paratively. When the radical cyclizations of thienyl and furyl
substituted alkenes are compared, thienyl substituted alkenes
formed trifluoromethyl ketone containing dihydrofurans in by far
higher yields than those of furyl substituted alkenes. This can be
explained by that the thienyl group make carbocation intermediate
more stable than furyl groups since % aromaticity of thiophene is
more than furan.
On the other hand, treatment of 1a and 1b with 2-isopropen-
ylthiophene (2d) gave the corresponding dihydrofuran containing
trifluoromethyl ketone in good yields. The radical cyclization of
4,4,4-trifluoro-1-phenylbutane-1,3-dione 1c and 4,4,4-trifluoro-1-
(2-naphthyl)butane-1,3-dione 1d with 2d afforded 3-trifluoro-
acetyl-dihydrofurans 3e and 3f as well as 2-trifluoromethyl-dihy-
drofurans 4a and 4b, formation of these compounds are explained
in the Scheme 2.
The radical intermediate H formed by the addition of an elec-
tron from 2d to Mn(III)eenolate complex is oxidized to carboca-
tion I. While the cyclization of this intermediate gives
3-trifluoroacetyl-4,5-dihydrofurans K (3e, 3f), J the other enol
form of I produces 2-trifluoromethyl-4,5-dihydrofurans L (4a, 4b).
Compounds K and L were differentiated by the chemical shifts of
carbonyl groups and carbons C-2 in 13C NMR spectra. Whereas the
carbonyl carbon of compound K gives quartet (2JCeF¼34.5 Hz) at
175 ppm in 13C NMR, the carbonyl carbon of compound L gives
singlet at 190 ppm. On the other hand, while C-2 of K gives singlet
at 172 ppm, C-2 carbon of L gives quartet (2JCeF¼34.4 Hz) at
150 ppm.
This study shows that radical cyclizations of 1,3-dicarbonyl
compounds with alkenes follow mostly the dominant enol form
of 1,3-dicarbonyl and in some cases follow both enol forms
depending on the structure of 1,3-dicarbonyl. Moreover, this study
exhibits heteroaromatic groups on alkene have a significant role in
the radical cyclizations. The cyclizations of 1,2-disubstituted al-
kenes (2b, 2c) occur only on C-1 carbon of the alkenes leading to
formations of tetrasubstitued-4,5-dihydrofurans. This study in-
troduces that fluorinated 1,3-dicarbonyl compounds can
be used effectively for synthesis of dihydrofurans containing
trifluoromethyl and trifluoromethyl ketone in this radical
cyclization.
3. Experimental
3.1. General
Fluorinated 1,3-dicarbonyls 1aef are available commercial
products and used in highest purity. 2-[(E)-2-Phenylvinyl]furan
2a,9 2-methyl-5-[(E)-2-phenylvinyl]furan 2b,10 and 2-[(E)-2-
phenylvinyl]thiophene 2c11 were prepared by the reaction of tri-
phenylphosphoniumbenzyl bromide and suitable aldehyde in NaH/
THF. 2-Isopropenylthiophene 2d was prepared by the reaction of
triphenylphosphoniummethyl bromide and 2-acetylthiophene in
NaH/THF.12 The other conjugated alkenes 2eeh were prepared by
dehydration from the carbinole formed Grignard reaction of aryl-
magnesium bromide and suitable carbonyl compounds.13 All con-
jugated alkenes were freshly prepared before used in the radical
When the radical cyclizations of 2-(1-phenylvinyl)furan (2e)
and 2-(1-phenylvinyl)thiophene (2f) with 1,3-dicarbonyls are
compared, it was observed that the reactions of 2f formed corre-
sponding products in much more higher yields than those of 2e
(Table 2). We previously reported the reaction of 1a with 1,1-
diphenyl ethylene in 78% yield.6i We obtained 3-trifluoroacetyl-
dihydrofuran in 87% yield from the reaction of 1a with 2f. This
result demonstrated that the alkene containing thienyl group has

M. Yılmaz / Tetrahedron 67 (2011) 8255e8263
8257
Table 1
Radical cyclization of fluorinated 1,3-dicarbonyl compounds with 2aed
Entry
1,3-Dicarbonyl
Alkene
Dihydrofuran
Yielda (%)
1
No product
2
3a, 12 dr¼88:12
3
4
3b, 17 dr¼85:15
3c, 88
5
6
2d
2d
3d, 85
7
2d
a
Yield of isolated product based on the alkene.
cyclizations. Radical reactions were performed at 1.2:1:2.5 molar
ratio (1:2:Mn(OAc)3) under nitrogen atmosphere in AcOH. All
compounds purified by column chromatography or preparative TLC
were characterized by IR, 1H, 13C, 19F NMR, mass spectra and
microanalysis.
Melting points were determined on an electrothermal capillary
melting point apparatus. IR spectra (KBr disc, CHCl3) were obtained
with a Matson 1000 FT-IR in the 400e4000 cmꢀ1 range with
4 cmꢀ1 resolution. 1H, 19F, and 13C NMR spectra were recorded on
a Bruker Avance DPX-400 MHz and Varian Mercury-400 High
performance Digital FT-NMR spectrophotometers. The mass spec-
tra were measured on a Waters 2695 Alliance Micromass ZQ (ESIþ)
LC/MS spectrophotometer. Elemental analyses were performed on
a Leco 932 CHNS-O instrument. Thin layer chromatography (TLC)
was performed on Merck aluminum-packed silica gel plates. Puri-
fication of the products was performed by column chromatography
3.2. Synthesis of 2-isopropenylthiophene (2d)12
To a solution of methyltriphenylphosphonium bromide (7.50 g,
21 mmol) in anhydrous THF in a three-necked flask fitted with
reflux condenser, thermometer, and magnetic stirrer, NaH (0.88 g,
22 mmol, in 60% mineral oil) was added. This mixture was heated at
60 ꢁC for 1 h 2-Acetylthiophene (2.52 g, 20 mmol) was added to
this mixture by dropwise, with stirring and cooling in ice, the re-
action temperature was maintained between 5 and 10 ꢁC. The
temperature was then rapidly taken to reflux for 2 h, and standing
overnight at room temperature. After this time, precipitated NaBr
was removed by filtering through a funnel with porosity 4. The
filtrate was evaporated in vacuum and the residue was extracted
with hexane (5ꢂ30 mL). The organic phase was dried with Na2SO4
and evaporated. The crude product was purified by column chro-
matography using hexane as eluent. Yield 63% (1.56 g) as colorless
flammable liquid bp 210e212 ꢁC, (lit. bp 60e61 ꢁC, 15 Torr).12a dH
(400 MHz, CDCl3) 7.14 (1H, d, J¼5.2 Hz), 7.01 (1H, d, J¼3.6 Hz), 6.95
on silica gel (Merck silica gel 60, 40e63 mm) or preparative TLC on
silica gel of Merck (PF254e366nm).

8258
M. Yılmaz / Tetrahedron 67 (2011) 8255e8263
olefin); dC (100 MHz, CDCl3) 144.7, 143.3, 141.0, 128.3, 128.2, 128.0,
127.2, 126.5, 125.0, 113.6; dC (100 MHz, CDCl3) 154.3, 142.6, 139.8,
139.5, 129.0, 128.5, 128.4, 128.2, 112.3, 111.5, 109.4.
Mn+3
O
Mn+2
O
O
O
Ar
CF3
S
Ar
CF3
3.3.3. Synthesis of 2-[1-(4-methylphenyl)vinyl]thiophene (2g). Yield
81% (810 mg) as a white solid mp 114e116 ꢁC. Found: C, 78.18; H,
6.22 C13H12S requires C, 77.95; H, 6.04%; nmax (KBr disc) 3024, 1595
(C]C), 1575, 1020, 783, 748, 692; dH (400 MHz, CDCl3) 7.33 (2H, d,
J¼6.9 Hz), 7.22e7.15 (3H, m), 6.94 (2H, m), 5.54 (1H, s, H-olefin),
5.22 (1H, s, H-olefin), 2.38 (3H, s, Me); dC (100 MHz, CDCl3) 144.9,
143.2, 138.1, 137.8, 128.8, 128.2, 127.2, 126.3, 124.9, 113.0, 21.2 (Me);
LC/MS, m/z (ESIþ) 201 (MHþ, 100%).
S
H
2d
1c
Ar = Ph :
Mn(OAc)3
1d
2-naphtyl :
3.3.4. Synthesis of 2-[1-(4-fluorophenyl)vinyl]thiophene (2h). Yield
77% (785 mg) as colorless oil. Found: C, 70.38; H, 4.32; S, 15.54
C12H9FS requires C, 70.56; H, 4.44; S, 15.70%; nmax (KBr disc) 3022,
1600, 1500,1492, 1112, 800, 839, 723; dH (400 MHz, CDCl3) 7.40 (2H,
dd, J¼10.0, 7.6 Hz), 7.23 (1H, dt, J¼6.8, 1.2 Hz), 7.03 (2H, m), 6.97
(1H, dd, J¼4.8, 1.2 Hz), 6.87 (1H, d, J¼4.8 Hz), 5.55 (1H, s), 5.19 (1H,
Mn+2
O
Mn+2
O
O
O
Ar
CF3
Ar
CF3
1
I
J
s); dC (100 MHz, CDCl3) 164.3, 161.0 (d, JCeF¼294.3 Hz), 144.59,
S
S
4
3
142.3, 137.0 (d, JCeF¼3.1 Hz), 130.0 (d, JCeF¼9.6 Hz), 127.3, 126.4,
125.2, 114.9 (d, 2JCeF¼25.9 Hz), 113.6; dF (376 MHz, CDCl3) ꢀ110 (1F,
s); LC/MS, m/z (ESIþ) 205 (MHþ, 100%).
S
S
3.4. General procedure for dihydrofurans
O
O
CF3
Ar
Ar
CF3
A solution of manganese(III) acetate dihydrate (2.5 mmol,
0.67 g) in 10 mL of glacial acetic acid was heated under a nitrogen
atmosphere at 80 ꢁC until it dissolved. After Mn(OAc)3 dissolved
completely, the solution was cooled down to 60 ꢁC. A solution of
trifluoromethyl-1,3-dicarbonyl compound (1.25 mmol) and alkene
(1 mmol) in 5 mL of acetic acid was added to this mixture and the
temperature was raised to 80e100 ꢁC. The reaction was complete
when the dark brown color of the solution disappeared. The acetic
acid was evaporated under reduced pressure. 30 mL of water was
added to the residue and extraction was performed with CHCl3
(3ꢂ20 mL). The combined organic extracts were neutralized with
10 mL of satd NaHCO3 solution, and dried over anhydrous Na2SO4
and evaporated. The crude products were purified by column
chromatography or preparative TLC (20ꢂ20 cm plates, 2 mm
thickness) using n-hexane/EtOAc (5:1) as eluent.
K
L
O
O
4a
3e
Ar = Ph :
2-naphtyl :
Ar = Ph :
2-naphtyl :
4b
3f
Scheme 2. Mechanism for the formation of 4a and 4b.
(1H, dd, J¼5.2, 3.6 Hz), 5.37 (1H, s, CH]), 4.96 (1H, s, CH]), 2.14
(3H, s, Me).
3.3. General procedure for 1,1-disubstituted alkenes (2eeh)
To a solution of arylmagnesium bromide obtained from the
Grignard reaction of suitable aryl bromide (60 mmol) and magne-
sium (1.73 g, 72 mmol) in 30 mL dried ether, the ketone was added
(50 mmol) by dropwise with cooling and stirring in ice-salt bath.
Then the reaction mixture was heated at reflux for 2 h. After this
time, the reaction mixture was hydrolyzed with 10% NH4Cl on ice-
salt bath, this mixture standing overnight and extracted with three
50 mL portion of ether. The combined organic phases were neu-
tralized with satd NaHCO3 and dried. Without purification, the
crude product in THF was dehydrated with 15% HCl. Upon com-
pletion, 20 mL of water was added to the mixture and it was
extracted with chloroform (3ꢂ50 mL). The combined organic
phases were neutralized with satd NaHCO3, dried, and evaporated.
The crude product was purified by column chromatography using
n-hexane as eluent.
3.4.1. 2,2,2-Trifluoro-1-[50-methyl-3-phenyl-5-(thiophen-2-yl)-2,3-
dihydro-2,20-bifuran-4-yl]ethanone (3a). Yield 12% (48 mg) as yel-
low oil. Found: C, 62.08; H, 3.43; S, 8.15 C21H15F3O3S requires C,
62.37; H, 3.74; S, 7.93%; Rf (20% EtOAc/hexane) 0.46; nmax (KBr disc)
2922, 2853, 1641 (C]O), 1596 (C]C), 1533, 1199 (CF3), 752, 700; dH
(300 MHz, CDCl3) 8.43 (1H, dd, J¼3.9, 1.2 Hz), 7.65 (1H, dd, J¼5.1,
1.2 Hz), 7.29e7.12 (6H, m), 6.28 (1H, d, J¼3.3 Hz), 5.90 (1H, dq,
J¼3.0, 0.9 Hz), 5.38 (1H, d, J¼4.2 Hz, H2), 4.85 (1H, dd, J¼4.2,
5JHeF¼1.2 Hz, H3), 2.24 (3H, s, Me); dC (75 MHz, CDCl3) 174.2 (q,
2JCeF¼34.5 Hz, C]O), 166.1 (C5), 152.9, 148.2, 141.2, 134.6, 133.0,
129.5, 127.9, 126.7 (2CH]), 126.6 (2CH]), 125.9, 115.8 (q,
1JCeF¼290.0 Hz, CF3), 109.4, 105.5 (C4), 84.7 (C2), 50.7 (q,
4JCeF¼2.8 Hz, C3), 28.1, 12.7 (Me); dF (282 MHz, CDCl3) ꢀ84.05 (s,
eCF3); LC/MS, m/z (ESIþ) 405 (MHþ, 100%).
3.3.1. Synthesis of 2-(1-phenylvinyl)furan (2e)13a. Yield 75% (6.40 g)
as colorless oil (lit. 105e107 ꢁC, 2 Torr).13a dH (400 MHz, CDCl3) 7.59
(1H, dd, J¼7.6,1.2 Hz), 7.42 (2H, m), 7.36 (3H, m), 6.38 (1H, dd, J¼3.6,
2.0 Hz), 6.19 (1H, d, J¼3.2 Hz), 5.74 (1H, d, J¼1.2 Hz), 5.22 (1H, d,
J¼1.2 Hz).
3.4.2. 2,2,2-Trifluoro-1-[4-phenyl-2,5-di(thiophen-2-yl)-4,5-
dihydrofuran-3-yl]ethanone (3b). Yield 17% (69 mg) as a yellow
solid mp 58e60 ꢁC. Found: C, 58.95; H, 3.12; S, 15.95 C20H13F3O2S2
requires C, 59.10; H, 3.22; S, 15.78%; Rf (20% EtOAc/hexane) 0.43;
nmax (KBr disc) 3046, 2951, 1671 (C]O), 1537 (C]C), 1136 (CeOeC),
729, 700; dH (400 MHz, CDCl3) 7.36e7.34 (3H, m), 7.25e7.22 (4H,
m), 7.15 ( 1H, dt, J¼3.2, 1.2 Hz), 7.03 (1H, dd, J¼5.2, 3.6 Hz), 5.77 (1H,
3.3.2. Synthesis of 2-(1-phenylvinyl)thiophene (2f)13bee. Yield 88%
(8.20 g) as colorless oil. dH (400 MHz, CDCl3) 7.46e7.41 (2H, m),
7.38e7.32 (3H, m), 7.23 (1H, dd, J¼4.8, 1.2 Hz), 6.98 (1H, dd, J¼4.8,
3.2 Hz), 6.91 (1H, J¼3.6, 2.0 Hz), 5.58 (1H, s, H-olefin), 5.24 (1H, s, H-
5
d, J¼3.6 Hz, H5), 4.84 (1H, dd, J¼3.2, JHeF¼1.6 Hz, H4); dC
2
(100 MHz, CDCl3) 175.4 (q, JCeF¼35.1 Hz, C]O), 169.1 (C2), 142.0,

M. Yılmaz / Tetrahedron 67 (2011) 8255e8263
8259
Table 2
Radical cyclization of fluorinated 1,3-dicarbonyl compounds with 2e and 2f
Entry 1,3-Dicarbonyl
Alkene
Dihydrofuran
Yielda (%)
1
3g, 36
3h, 33
3i, 87
3j, 90
3k, 79
3l, 85
2
3
4
5
6
2e
2f
2f
2f
7
2f
2f
3m, 74
8
3n, 77
a
Yield of isolated product based on the alkene.
137.1, 135.8, 134.3, 129.1, 128.3, 128.1, 127.9, 127.8, 126.9 (2CH]),
126.4 (2CH]), 125.8, 117.3 (q, 1JCeF¼289.6 Hz, CF3), 107.3 (C3), 88.3
(C5), 55.8 (C4); dF (376 MHz, CDCl3) ꢀ76.4 (s, CF3); LC/MS, m/z
(ESIþ) 407 (MHþ, 100%).
J¼5.1, 3.9 Hz), 6.95 (1H, dd, J¼3.6, 1.2 Hz), 6.83 (1H, dd, J¼5.1,
5
3.6 Hz), 3.55 (1H, dd, J¼15.0, JHeF¼0.9 Hz, Hb-4), 3.34 (1H, dd,
5
J¼15.0, JHeF¼0.9 Hz, Ha-4), 1.81 (3H, s, Me); dC (75 MHz, CDCl3)
2
174.5 (q, JCeF¼34.6 Hz, C]O), 165.4 (C2), 147.9, 135.6, 134.1, 131.1,
128.1, 127.2, 125.6, 124.0, 117.3 (q, 1JCeF¼289.6 Hz, CF3), 103.1 (C3),
88.6 (C5), 44.1 (d, 4JCeF¼3.3 Hz, C4), 28.8 (Me); dF (282 MHz, CDCl3)
ꢀ76.4 (s, CF3); LC/MS, m/z (ESIþ) 345 (MHþ, 100%).
3.4.3. 2,2,2-Trifluoro-1-[5-methyl-2,5-di(thiophen-2-yl)-4,5-
dihydrofuran-3-yl]ethanone (3c). Yield 88% (303 mg) as a light
yellow solid mp 75e77 ꢁC. Found: C, 52.02; H, 3.34; S, 18.84
C15H11F3O2S2 requires C, 52.32; H, 3.22; S, 18.62%; Rf (20% EtOAc/
hexane) 0.50; nmax (KBr disc) 3061, 1670 (C]O), 1538 (C]C), 1136
(CeOeC), 729, 700; dH (300 MHz, CDCl3) 8.39 (1H, dd, J¼3.9,1.2 Hz),
7.50 (1H, dd, J¼5.1, 1.2 Hz), 7.10 (1H, dd, J¼5.1, 1.2 Hz), 7.02 (1H, dd,
3.4.4. 2,2,2-Trifluoro-1-[5-methyl-5-(thiophen-2-yl)-4,5-dihydro-
2,20-bifuran-3-yl]ethanone (3d). Yield 85% (279 mg) as a pale yel-
low solid mp 88e90 ꢁC. Found: C, 54.96; H, 3.25; S, 9.60
C15H11F3O3S requires C, 54.88; H, 3.38; S, 9.77%; Rf (20% EtOAc/

8260
M. Yılmaz / Tetrahedron 67 (2011) 8255e8263
Table 3
Radical cyclization of fluorinated 1,3-dicarbonyl compounds with 2g and 2h
Entry 1,3-Dicarbonyl
Alkene
Dihydrofuran
Yielda (%)
1
3o, 81
2
3
2g
2g
3p, 83
3q, 80
4
3r, 89
5
6
2h
2h
3s, 92
3t, 75
7
2h
2h
3u, 88
3v, 70
8
a
Yield of isolated product based on the alkene.
hexane) 0.45; nmax (KBr disc) 1671 (C]O), 1539 (C]C), 1207 (CF3),
1136 (CeOeC); dH (300 MHz, CDCl3) 8.32 (1H, d, J¼3.6 Hz), 7.56 (1H,
d, J¼1.2 Hz), 7.20 (1H, dd, J¼5.1, 1.2 Hz), 7.04 (1H, dd, J¼3.6, 1.2 Hz),
6.90 (1H, dd, J¼5.1, 3.6 Hz), 6.53 (1H, dd, J¼3.6, 1.5 Hz), 3.60 (1H, dd,
J¼14.7, 5JHeF¼0.6 Hz, Hb-4), 3.37 (1H, dd, J¼15.0, 5JHeF¼0.6 Hz, Ha-
4), 1.91 (3H, s, Me); dC (75 MHz, CDCl3) 172.4 (q, 2JCeF¼34.0 Hz, C]
O), 159.3 (C2), 146.2, 145.7, 143.0, 125.9, 124.6, 123.1, 121.4, 116.1 (q,
1JCeF¼289.2 Hz, CF3), 111.7, 102.1 (C3), 87.9 (C5), 42.5 (d,
4JCeF¼3.3 Hz, C4), 27.5 (Me); dF (282 MHz, CDCl3) ꢀ84.0 (s, CF3); LC/
MS, m/z (ESIþ) 329 (MHþ, 100%).
3.4.5. 2,2,2-Trifluoro-1-[5-methyl-2-phenyl-5-(thiophen-2-yl)-4,5-
dihydrofuran-3-yl]ethanone (3e). Yield 73% (247 mg) as yellow oil.
Found: C, 60.52; H, 3.56; S, 9.66 C17H13F3O2S requires C, 60.35; H,
3.87; S, 9.48%; Rf (20% EtOAc/hexane) 0.55; nmax (KBr disc) 3061,
2965, 2870, 1666 (C]O), 1531 (C]C), 1199 (CF3), 1140 (CeOeC),

M. Yılmaz / Tetrahedron 67 (2011) 8255e8263
8261
731, 700; dH (300 MHz, CDCl3) 7.91 (1H, dd, J¼6.9, 1.5 Hz), 7.60 (1H,
tt, J¼7.5,1.5 Hz), 7.49 (2H, t, J¼7.5 Hz), 7.35 (1H, tt, J¼5.1,1.2 Hz), 7.17
(1H, dd, J¼3.9, 1.5 Hz), 7.06 (1H, dd, J¼5.1, 3.6 Hz), 3.74 (1H, dd,
J¼14.7, 5JHeF¼0.9 Hz, Hb-4), 3.51 (1H, dd, J¼14.7, 5JHeF¼0.9 Hz, Ha-
4), 2.03 (3H, s, Me); dC (75 MHz, CDCl3) 175.6 (q, 2JCeF¼34.6 Hz, C]
O), 172.2 (C2), 147.9, 132.3, 129.9, 129.1, 128.2, 127.2 (2CH]), 125.7
(2CH]), 124.0, 117.2 (q, 1JCeF¼290.7 Hz, CF3), 104.6 (C3), 88.8 (C5),
44.3 (d, 4JCeF¼3.3 Hz, C4), 28.8 (Me); dF (282 MHz, CDCl3) ꢀ74.2 (s,
CF3); LC/MS, m/z (ESIþ) 339 (MHþ, 100%).
C4); dF (376 MHz, CDCl3) ꢀ76.4 (s, CF3); LC/MS, m/z (ESIþ) 407
(MHþ, 100%).
3.4.10. 2,2,3,3,4,4,4-Heptafluoro-1-[5-phenyl-2,5-di(thiophen-2-yl)-
4,5-dihydrofuran-3-yl]butan-1-one (3j). Yield 90% (455 mg) as
a pale yellow solid mp 79e81 ꢁC. Found: C, 52.49; H, 2.27; S, 12.86
C22H13F7O2S2 requires C, 52.17; H, 2.59; S, 12.66%; Rf (20% EtOAc/
hexane) 0.47; nmax (KBr disc) 3046, 1672 (C]O), 1537, 1215, 729,
700; dH (400 MHz, CDCl3) 8.56 (1H, d, J¼4.0 Hz), 7.66 (1H, d,
J¼5.2 Hz), 7.49 (2H, d, J¼7.6 Hz), 7.38 (2H, t, J¼7.2 Hz), 7.26 ( 1H, dt,
J¼5.2, 1.2 Hz), 7.18 (1H, t, J¼4.4 Hz), 6.98 (1H, dt, J¼3.6, 1.2 Hz), 6.92
(1H, tt, J¼4.4, 1.2 Hz), 4.17 (1H, d, J¼15.2 Hz, Hb-4), 3.94 (1H, d,
3.4.6. 2,2,2-Trifluoro-1-[5-methyl-2-(naphthalen-2-yl)-5-(thiophen-
2-yl)-4,5-dihydrofuran-3-yl]ethanone (3f). Yield 61% (237 mg) as
yellow oil. Found: C, 65.17; H, 3.80; S, 8.43 C21H15F3O2S requires C,
64.94; H, 3.89; S, 8.26%; Rf (20% EtOAc/hexane) 0.50; nmax (KBr disc)
3065, 2967, 2930, 1660 (C]O), 1585 (C]C), 1548, 1197 (CF3), 1141
(CeOeC), 756, 696; dH (300 MHz, CDCl3) 8.38 (1H, s), 7.85e7.71 (4H,
m), 7.45 (2H, m), 7.22 (1H, dd, J¼5.1, 1.2 Hz), 7.05 (1H, dd, J¼3.6,
1.2 Hz), 6.92 (1H, dd, J¼4.8, 0.6 Hz), 3.63 (1H, dd, J¼14.7,
5JHeF¼0.9 Hz, Hb-4), 3.42 (1H, dd, J¼14.7, 5JHeF¼0.9 Hz, Ha-4), 1.92
(3H, s, Me); dC (75 MHz, CDCl3) 174.5 (q, 2JCeF¼34.5 Hz, C]O), 172.1
(C2), 147.8, 135.0, 132.3, 131.1, 129.3, 128.2, 127.8, 127.6, 127.0, 126.7,
126.2, 125.6, 125.5, 123.9, 117.0 (q, 1JCeF¼289.7 Hz, CF3), 104.7 (C3),
88.6 (C5), 44.3 (q, 4JCeF¼3.3 Hz, C4), 28.8 (Me); dF (282 MHz, CDCl3)
ꢀ73.7 (s, CF3); LC/MS, m/z (ESIþ) 389 (MHþ, 100%).
2
J¼15.2 Hz, Ha-4); dC (100 MHz, CDCl3) 176.9 (t, JCeF¼25.1 Hz, C]
O), 165.7 (C2), 147.5, 143.3, 135.9, 134.4, 131.0, 128.9, 128.6, 128.2,
1
127.0, 126.8, 126.4 (2CH]), 125.5, 118.0 (qt, JCeF¼286.5,
1
2
2JCeF¼33.5 Hz, eCF2CF2CF3), 110.5 (tt, JCeF¼266.7, JCeF¼31.2 Hz,
1
2
2
eCF2CF2CF3), 109.2 (tqt, JCeF¼264.4, JCeF¼38.1, JCeF¼31.2 Hz,
5
eCF2CF2CF3), 105.1 (C3), 91.4 (t, JCeF¼2.3 Hz, C5), 44.8 (t,
4JCeF¼6.9 Hz, C4); dF (376 MHz, CDCl3) ꢀ126.4 (2F, s, eCF2CF2CF3),
ꢀ118.0 (2F, dq, JFeF¼53.0, 9.0 Hz, eCF2CF2CF3), ꢀ80.6 (3F, t,
3JFeF¼9.0 Hz, eCF2CF2CF3); LC/MS, m/z (ESIþ) 507 (MHþ, 100%).
3.4.11. 2,2,2-Trifluoro-1-[5-phenyl-5-(thiophen-2-yl)-4,5-dihydro-
2,20-bifuran-3-yl]ethanone (3k). Yield 65% (254 mg) as yellow oil.
Found: C, 61.64; H, 3.54; S, 8.04 C20H13F3O3S requires C, 61.53; H,
3.36; S, 8.21%; Rf (20% EtOAc/hexane) 0.43; nmax (KBr disc) 3028,
2922, 1685 (C]O), 1585, 1556 (C]C), 1209 (CF3), 1136 (CeOeC),
758, 692; dH (400 MHz, CDCl3) 8.43 (1H, d, J¼3.6 Hz), 7.71 (1H, t,
J¼0.8 Hz), 7.56 (2H, dd, J¼8.0, 1.6 Hz), 7.45e7.38 (4H, m), 7.33 (1H,
dd, J¼4.8, 1.2 Hz), 7.01 (1H, dd, J¼4.0, 1.6 Hz), 6.97 (1H, t,
J¼3.6 Hz), 6.64 (1H, dd, J¼3.6, 1.6 Hz), 4.17 (1H, d, J¼15.2 Hz, Hb-
4), 3.95 (1H, d, J¼15.2 Hz, Ha-4); dC (100 MHz, CDCl3) 174.3 (q,
2JCeF¼34.6 Hz, C]O), 160.3 (C2), 147.3, 147.1, 144.3, 143.2, 128.8,
128.7, 127.0, 126.9, 126.8 (2CH]), 125.6, 122.9, 117.4 (q,
1JCeF¼288.8 Hz, CF3), 113.2, 103.6 (C3), 91.9 (C5), 44.5 (d,
4JCeF¼3.0 Hz, C4); dF (376 MHz, CDCl3) ꢀ76.2 (s, CF3); LC/MS, m/z
(ESIþ) 391 (MHþ, 100%).
3.4.7. 2,2,2-Trifluoro-1-[2-phenyl-5-(thiophen-2-yl)-2,3-dihydro-
2,20-bifuran-4-yl]ethanone (3g). Yield 36% (140 mg) as yellow oil.
Found: C, 61.75; H, 3.05; S, 8.42 C20H13F3O3S requires C, 61.53; H,
3.36; S, 8.21%; Rf (20% EtOAc/hexane) 0.45; nmax (KBr disc) 2870,
1666 (C]O), 1531 (C]C), 1199 (CF3), 1140 (CeOeC), 731, 700; dH
(400 MHz, CDCl3) 8.61 (1H, dd, J¼2.4, 1.2 Hz), 7.74 (1H, dd, J¼4.0,
1.2 Hz), 7.52e7.40 (6H, m), 7.25 (1H, m), 6.36 (1H, dd, J¼3.2,
1.6 Hz), 6.21 (1H, dd, J¼5.6, 2.0 Hz), 4.24 (1H, d, J¼14.8 Hz, Hb-3),
3.74 (1H, d, J¼14.8 Hz, Ha-3); dC (100 MHz, CDCl3) 174.5 (q,
2JCeF¼34.3 Hz, C]O), 164.9 (C5), 153.9, 143.8, 142.0, 141.4, 135.3,
133.8, 128.6, 128.5 (2CH]), 127.9 (2CH]), 125.3, 117.2 (q,
1JCeF¼289.6 Hz, CF3), 110.4, 109.9, 103.0 (C4), 88.5 (C2), 41.5 (q,
4JCeF¼3.0 Hz, C3); dF (376 MHz, CDCl3) ꢀ74.4 (s, CF3); LC/MS, m/z
(ESIþ) 391 (MHþ, 100%).
3.4.12. 1-[2,5-Diphenyl-5-(thiophen-2-yl)-4,5-dihydrofuran-3-yl]-
2,2,2-trifluoroethanone (3l). Yield 85% (340 mg) as a colorless cubic
crystal mp 103e105 ꢁC. Found: C, 66.13; H, 3.58; S, 8.21 C22H15F3O2S
requires C, 65.99; H, 3.78; S, 8.01%; Rf (20% EtOAc/hexane) 0.48;
nmax (KBr disc) 3059, 2963, 2870, 1681 (C]O), 1583 (C]C), 1550,
1490, 1448, 1269, 1205 (CF3), 1140 (CeOeC), 883, 760, 696; dH
(400 MHz, CDCl3) 7.97 (2H, dd, J¼8.5, 1.2 Hz), 7.59 (2H, d, J¼7.4 Hz),
7.51e7.408 (6H, m), 7.37 (1H, dd, J¼4.9, 0.9 Hz), 7.06 (1H, dd, J¼3.6,
1.0 Hz), 7.03 (1H, t, J¼4.8 Hz), 4.20 (1H, d, J¼14.8 Hz, Hb-4), 4.00
(1H, d, J¼14.8 Hz, Ha-4); dC (100 MHz, CDCl3) 175.3 (q,
2JCeF¼34.6 Hz, C]O), 171.6 (C2), 147.7, 143.3, 132.2, 129.8, 128.8
(2CH]), 128.7, 128.4, 128.1, 126.8 (2CH]), 126.6 (2CH]), 126.1
(2CH]), 125.4, 116.8 (q, 1JCeF¼291.4 Hz, CF3), 104.9 (C3), 91.4 (C5),
3.4.8. 1-(2,5-Diphenyl-2,3-dihydro-2,20-bifuran-4-yl)-2,2,2-
trifluoroethanone (3h). Yield 33% (127 mg) as yellow oil. Found: C,
68.51; H, 4.12 C22H15F3O3 requires C, 68.75; H, 3.93%; Rf (20% EtOAc/
hexane) 0.46; nmax (KBr disc) 3030, 2932, 1670 (C]O), 1533 (C]C),
1145 (CeOeC), 756, 700; dH (300 MHz, CDCl3) 7.80 (2H, dd, J¼7.5,
1.5 Hz), 7.36 (9H, m), 6.25 (1H, dd, J¼3.3,1.2 Hz), 6.08 (1H, dd, J¼3.3,
0.9 Hz), 4.09 (1H, d, J¼15.0 Hz, Hb-3), 3.62 (1H, d, J¼15.0 Hz, Ha-3);
dC (75 MHz, CDCl3) 175.8 (q, 2JCeF¼34.4 Hz, C]O), 172.1 (C5), 154.4,
144.1, 141.8, 132.4, 130.0, 129.0, 128.9 (2CH]), 128.8 (2CH]), 128.3
(2CH]), 125.7 (2CH]), 117.2 (q, 1JCeF¼290.2 Hz, CF3), 110.7, 110.2,
105.0 (C4), 89.0 (C2), 41.9 (q, 4JCeF¼3.3 Hz, C3); dF (282 MHz, CDCl3)
ꢀ74.5 (s, CF3); LC/MS, m/z (ESIþ) 385 (MHþ, 100%).
4
44.8 (d, JCeF¼3.5 Hz, C4); dF (376 MHz, CDCl3) ꢀ76.4 (s, CF3); LC/
MS, m/z (ESIþ) 401 (MHþ, 100%).
3.4.9. 2,2,2-Trifluoro-1-[5-phenyl-2,5-di(thiophen-2-yl)-4,5-
dihydrofuran-3-yl]ethanone (3i). Yield 87% (353 mg) as a pale yel-
low needle crystal mp 87e89 ꢁC. Found: C, 59.27; H, 3.34; S, 15.54
C20H13F3O2S2 requires C, 59.10; H, 3.22; S, 15.78%; Rf (20% EtOAc/
hexane) 0.46; nmax (KBr disc) 3028, 1685 (C]O), 1583 (C]C), 1556,
1213 (CF3), 1138 (CeOeC), 756, 696; dH (400 MHz, CDCl3) 8.67 (1H,
dd, J¼4.0, 0.7 Hz), 7.75 (1H, d, J¼5.8 Hz), 7.58 (2H, dd, J¼8.6, 1.1 Hz),
7.47e7.40 (3H, m), 7.35 (1H, dd, J¼4.9, 0.8 Hz), 7.26 (1H, t, J¼4.4 Hz),
7.06 (1H, d, J¼3.3 Hz), 7.00 (1H, dd, J¼4.8, 3.8 Hz), 4.21 (1H, d,
J¼14.8 Hz, Hb-4), 4.00 (1H, d, J¼14.8 Hz, Ha-4); dC (100 MHz, CDCl3)
3.4.13. 2,2,2-Trifluoro-1-[2-(naphthalen-2-yl)-5-phenyl-5-(thiophen-
2-yl)-4,5-dihydrofuran-3-yl]ethanone (3m). Yield 74% (333 mg) as
yellow oil. Found: C, 69.02; H, 3.58; S, 7.01 C26H17F3O2S requires C,
69.32; H, 3.80; S, 7.12%; Rf (20% EtOAc/hexane) 0.48; nmax (KBr disc)
3055, 2930, 2861, 1681 (C]O), 1589 (C]C), 1544, 1448, 1276, 1199
(CF3), 1143 (CeOeC), 758, 694; dH (400 MHz, CDCl3) 8.53 (1H, s),
7.91e7.80 (4H, m), 7.54e7.49 (4H, m), 7.38 (2H, t, J¼7.6 Hz), 7.33 (1H,
d, J¼7.6 Hz), 7.28 (1H, d, J¼5.2 Hz), 6.98 (1H, d, J¼3.6 Hz), 6.94 (1H, t,
J¼4.0 Hz), 4.15 (1H, d, J¼14.8 Hz, Hb-4), 3.95 (1H, d, J¼14.8 Hz, Ha-4);
dC (100 MHz, CDCl3) 175.3 (q, 2JCeF¼34.3 Hz, C]O), 171.9 (C2), 147.9,
143.6, 135.4, 132.5, 131.5 (2CH]), 129.5 (2CH]), 128.9, 128.7, 128.5,
128.0, 127.9, 127.0, 126.9, 126.8, 126.3 (2CH]), 125.9, 125.7, 117.2 (q,
2
174.1 (q, JCeF¼36.3 Hz, C]O), 164.8 (C2), 147.4, 143.2, 135.5, 134.1,
130.8, 128.7, 128.5, 128.0, 126.8, 126.6, 126.2 (2CH]), 125.3, 117.2 (q,
4
1JCeF¼290.0 Hz, CF3), 103.2 (C3), 91.2 (C5), 44.6 (q, JCeF¼3.1 Hz,

8262
M. Yılmaz / Tetrahedron 67 (2011) 8255e8263
1JCeF¼290.3 Hz, CF3), 105.0 (C3), 91.7 (C5), 45.2 (C4); dF (376 MHz,
CDCl3) ꢀ74.0 (s, CF3); LC/MS, m/z (ESIþ) 451 (MHþ, 100%).
(q, J¼288.9 Hz, CF3), 105.1 (C3), 91.6 (C5), 44.9 (C4), 21.3 (Me); dF
(376 MHz, CDCl3) ꢀ7.4 (s, CF3); LC/MS, m/z (ESIþ) 415 (MHþ, 100%).
3.4.14. 2,2,2-Trifluoro-1-[2-methyl-5-phenyl-5-(thiophen-2-yl)-4,5-
dihydrofuran-3-yl]ethanone (3n). Yield 77% (260 mg) as yellow oil.
Found: C, 60.15; H, 4.02; S, 9.29 C17H13F3O2S requires C, 60.35; H,
3.87; S, 9.48%; Rf (20% EtOAc/hexane) 0.52; nmax (KBr disc) 3062,
1685 (C]O), 1583, 1556 (C]C), 1213 (CF3), 1137 (CeOeC), 875, 755,
696; dH (400 MHz, CDCl3) 7.47e7.37 (5H, m), 7.31 (1H, dd, J¼4.8,
1.2 Hz), 6.96 (2H, m), 3.95 (1H, d, J¼14.4 Hz, Hb-4), 3.71 (1H, d,
J¼14.4 Hz, Ha-4), 2.49 (3H, s, Me); dC (100 MHz, CDCl3) 176.2 (q,
2JCeF¼35.0 Hz, C]O), 175.7 (C2), 147.7, 143.4, 128.6, 128.4, 126.7,
3.4.18. 2,2,2-Trifluoro-1-[5-(4-fluorophenyl)-2,5-di(thiophen-2-yl)-
4,5-dihydrofuran-3-yl]ethanone (3r). Yield 89% (377 mg) as yellow
solid mp 82e84 ꢁC. Found: C, 56.45; H, 2.98; S, 15.35 C20H12F4O2S2
requires C, 56.60; H, 2.85; S,15.11%; Rf (20% EtOAc/hexane) 0.43; nmax
(KBrdisc)2940, 2862,1668(C]O),1569(C]C),1529,1477,1263(CF3),
1201 (CeOeC), 918, 850, 762, 700; dH (400 MHz, CDCl3) 8.48 (1H, dd,
J¼4.0, 1.2 Hz), 7.58 (1H, dd, J¼4.8, 1.2 Hz), 7.37 (2H, m), 7.20 (1H, dd,
J¼4.8, 1.2 Hz), 7.10 (1H, t, J¼4.4 Hz), 6.97 (1H, dd, J¼9.2, 2.0 Hz), 6.85
(1H, t, J¼4.0 Hz), 4.02 (1H, d, J¼15.2 Hz, Hb-4), 3.76 (1H, d, J¼15.2 Hz,
Ha-4); dC (100 MHz, CDCl3) 174.6 (q, 2JCeF¼34.3 Hz, C]O),164.9 (C2),
1
126.5, 126.0 (2CH]), 125.2, 116.7 (q, JCeF¼288.8 Hz, CF3), 105.5
4
(C3), 92.2 (C5), 43.7 (C4), 15.9 (Me); dF (376 MHz, CDCl3) ꢀ74.8 (s,
163.0 (d, 1JCeF¼246.1 Hz, Cipso), 139.2 (d, JCeF¼3.1 Hz), 135.7, 134.4,
CF3); LC/MS, m/z (ESIþ) 339 (MHþ, 100%).
130.8, 128.2, 127.5, 127.5 (d, 3JCeF¼8.4 Hz),127.0,126.9,126.4 (2CH]),
117.3 (q, 1JCeF¼288.8 Hz, CF3),115.7 (d, 2JCeF¼21.4 Hz),103.2 (C3), 90.9
4
3.4.15. 2,2,2-Trifluoro-1-[5-(4-methylphenyl)-2,5-di(thiophen-2-yl)-
4,5-dihydrofuran-3-yl]ethanone (3o). Yield 81% (340 mg) as yellow
solid mp 90e92 ꢁC. Found: C, 60.22; H, 3.95; S, 15.29 C21H15F3O2S2
requires C, 59.99; H, 3.60; S, 15.25%; Rf (20% EtOAc/hexane) 0.46;
nmax (KBr disc) 3028, 2924, 1687 (C]O), 1581 (C]C), 1323, 1201
(CF3), 1134 (CeOeC), 906, 816, 691; dH (400 MHz, CDCl3) 8.58 (1H,
dd, J¼4.4, 1.2 Hz), 7.67 (1H, dd, J¼5.2, 1.2 Hz), 7.39 (2H, d,
J¼8.4 Hz), 7.27 (1H, dd, J¼4.8, 1.6 Hz), 7.19 (1H, d, J¼0.8 Hz), 7.20
(2H, d, J¼8.4 Hz), 6.98 (1H, dd, J¼3.2, 1.2 Hz), 6.93 (1H, dd, J¼4.8,
3.6 Hz), 4.10 (1H, d, J¼15.2 Hz, Hb-4), 3.90 (1H, d, J¼15.2 Hz, Ha-
(C5), 44.8 (d, JCeF¼3.8 Hz, C4); dF (376 MHz, CDCl3) ꢀ110 (1F, m,
arom.CF), ꢀ74.3 (3F, s, CF3); LC/MS, m/z (ESIþ) 425 (MHþ, 100%).
3.4.19. 2,2,3,3,4,4,4-Heptafluoro-1-[5-(4-fluorophenyl)-2,5-
di(thiophen-2-yl)-4,5-dihydrofuran-3-yl]butan-1-one (3s). Yield 92%
(482 mg) as yellow solid mp 64e66 ꢁC. Found: C, 50.21; H, 2.15; S,
12.44 C22H12F8O2S2 requires C, 50.38; H, 2.31; S, 12.23%; Rf (20%
EtOAc/hexane) 0.48;nmax (KBrdisc)3031, 672(C]O),1538,1209, 729;
dH (400 MHz, CDCl3) 8.56 (1H, dd, J¼3.6, 1.2 Hz), 7.67 (1H, dd, J¼4.8,
1.2 Hz), 7.46 (2H, dd, J¼8.8, 1.2 Hz), 7.30 (1H, dd, J¼5.2, 1.2 Hz), 7.19
(1H, t, J¼4.8 Hz), 7.07(2H,t, J¼8.8 Hz), 6.98(1H,dd, J¼3.2,1.2 Hz), 6.95
(1H, t, J¼3.2 Hz), 4.16 (1H, d, J¼14.8 Hz, Hb-4), 3.91 (1H, dt, J¼14.8 Ha-
2
4), 2.35 (3H, s, Me); dC (100 MHz, CDCl3) 174.4 (q, JCeF¼34.3 Hz,
C]O), 165.1 (C2), 147.8, 140.5, 138.6, 135.7, 134.2, 131.1, 129.5,
1
2
128.2, 126.9, 126.7, 126.3 (2CH]), 125.5, 117.5 (q, JCeF¼289.5 Hz,
4); dC (100 MHz, CDCl3) 176.6 (t, JCeF¼25.1 Hz, C]O), 165.3 (C2),
4
4
CF3), 103.4 (C3), 91.4 (C5), 44.8 (d, JCeF¼3.1 Hz C4), 21.4 (Me); dF
162.6 (d, 1JCeF¼246.9 Hz, Cipso), 147.0, 139.0 (d, JCeF¼3.0 Hz), 135.7,
(376 MHz, CDCl3) ꢀ77.5 (s, CF3); LC/MS, m/z (ESIþ) 421 (MHþ,
134.3, 130.7, 128.0, 127.0 (d, 3JCeF¼7.7 Hz),126.8,126.7,126.2 (2CH]),
2
1
2
100%).
115.6 (d, JCeF¼21.4 Hz), 117.7 (qt, JCeF¼286.6, JCeF¼33.5 Hz,
eCF2CF2CF3),110.3 (tt,1JCeF¼266.0, 2JCeF¼31.2 Hz, eCF2CF2CF3),108.9
(tqt, 1JCeF¼264.0, 2JCeF¼38.1, 2JCeF¼31.2 Hz, eCF2CF2CF3), 104.7 (C3),
3.4.16. 2,2,3,3,4,4,4-Heptafluoro-1-[5-(4-methylphenyl)-2,5-
5
4
di(thiophen-2-yl)-4,5-dihydrofuran-3-yl]butan-1-one
(3p). Yield
90.7 (t, JCeF¼2.1 Hz, C5), 44.7 (t, JCeF¼6.9 Hz, C4); dF (376 MHz,
CDCl3) ꢀ126.5 (s, eCF2CF2CF3), ꢀ118.0 (dq, JFeF¼43.6, 9.4 Hz,
83% (432 mg) as a yellow solid mp 87e89 ꢁC. Found: C, 52.92; H,
2.83; S, 12.12 C23H15F7O2S2 requires C, 53.07; H, 2.90; S, 12.32%; Rf
(20% EtOAc/hexane) 0.5; nmax (KBr disc) 1671 (C]O), 1539, 1206,
1136, 732; dH (400 MHz, CDCl3) 8.55 (1H, dd, J¼3.6, 1.2 Hz), 7.65
(1H, dd, J¼5.2, 1.2 Hz), 7.38 (2H, d, J¼8.0 Hz), 7.26 (1H, dd, J¼5.2,
1.6 Hz), 7.19 (2H, d, J¼8.0 Hz), 7.18 (1H, d, J¼9.2 Hz), 6.97 (1H, dd,
J¼3.6, 1.2 Hz), 6.93 (1H, dd, J¼5.2, 3.6 Hz), 4.14 (1H, dt, J¼14.8,
5JHeF¼2.0 Hz, Hb-4), 3.93 (1H, dt, J¼14.8, 5JHeF¼0.8 Hz, Ha-4), 2.34
3
eCF2CF2CF3), ꢀ113.7 (1F, m, arom. CeF), ꢀ80.6 (3F, t, JFeF¼9.4 Hz,
eCF2CF2CF3); LC/MS, m/z (ESIþ) 525 (MHþ, 100%).
3.4.20. 2,2,2-Trifluoro-1-[5-(4-fluorophenyl)-5-(thiophen-2-yl)-4,5-
dihydro-2,20-bifuran-3-yl]ethanone (3t). Yield 75% (306 mg) as yel-
low oil. Found: C, 58.56; H, 3.14; S, 7.67 C20H12F4O3S requires C, 58.82;
H, 2.96; S, 7.85%; Rf (20% EtOAc/hexane) 0.41; nmax (KBr disc) 3028,
2922,1685 (C]O), 1585,1556 (C]C), 1209 (CF3), 1136 (CeOeC), 758,
702; dH (400 MHz, CDCl3) 8.42 (1H, d, J¼3.6 Hz), 7.70 (1H, d, J¼1.2 Hz),
7.53 (2H, dd, J¼6.8, 3.2 Hz), 7.33 (1H, dd, J¼4.8, 1.2 Hz), 7.12 (2H, t,
J¼8.4 Hz), 7.01e6.96 (2H, m), 6.64 (1H, dd, J¼3.6, 2.0 Hz), 4.14 (1H, d,
J¼15.2 Hz, Hb-4), 3.88 (1H, d, J¼15.2 Hz, Ha-4); dC (100 MHz, CDCl3)
173.5 (q, 2JCeF¼34.3 Hz, C]O), 162.6 (d, 1JCeF¼246.9 Hz, Cipso), 160.0
2
(3H, s, Me); dC (100 MHz, CDCl3) 176.6 (t, JCeF¼25.1 Hz, C]O),
165.5 (C2), 147.5, 140.2, 138.3, 135.6, 134.1, 130.9, 129.3, 127.9,
1
126.7, 126.5, 126.0 (2CH]), 125.3, 117.7 (qt, JCeF¼286.5,
1
2
2JCeF¼33.6 Hz, eCF2CF2CF3), 110.4 (tt, JCeF¼266.7, JCeF¼31.3 Hz,
1
2
2
eCF2CF2CF3), 108.9 (tqt, JCeF¼265.2, JCeF¼38.1, JCeF¼31.3 Hz,
5
eCF2CF2CF3), 104.9 (C3), 91.2 (t, JCeF¼2.3 Hz, C5), 44.6 (t,
4JCeF¼6.1 Hz, C4), 21.1 (Me); dF (376 MHz, CDCl3) ꢀ126.4 (2F, s,
eCF2CF2CF3), ꢀ118.0 (2F, dq, JFeF¼53.0, 9.2 Hz, eCF2CF2CF3), ꢀ80.6
(C2), 146.9, 146.8 (2CH]), 144.0, 138.9 (d, JCeF¼3.0 Hz), 127.3 (d,
4
1
3JCeF¼8.4 Hz, 2CH]), 126.8, 126.5, 122.7, 116.7 (q, JCeF¼287.0 Hz,
(3F, t, JFeF¼9.2 Hz, eCF2CF2CF3); LC/MS, m/z (ESIþ) 521 (MHþ,
CF3), 115.5 (d, 2JCeF¼21.3 Hz, 2CH]), 112.8, 103.2 (C3), 91.2 (C5), 44.3
3
4
100%).
(q, JCeF¼3.1 Hz, C4); dF (376 MHz, CDCl3) ꢀ110 (1F, m, arom.CF),
ꢀ74.4 (3F, s, CF3); LC/MS, m/z (ESIþ) 409 (MHþ, 100%).
3.4.17. 2,2,2-Trifluoro-1-[5-(4-methylphenyl)-2-phenyl-5-(thiophen-
2-yl)-4,5-dihydrofuran-3-yl]ethanone (3q). Yield 80% (331 mg) as
yellow oil. Found: C, 66.60; H, 4.22; S, 7.56 C23H17F3O2S requires C,
66.66; H, 4.13; S, 7.74%; Rf (20% EtOAc/hexane) 0.48; nmax (KBr disc)
3028, 2924, 1675 (C]O), 1569 (C]C), 1537, 1219 (CF3), 1180
(CeOeC), 918, 849, 818, 764; dH (400 MHz, CDCl3) 7.89 (2H, dd,
J¼7.2, 1.6 Hz), 7.52 (1H, t, J¼7.6 Hz), 7.44 (2H, t, J¼7.6 Hz), 7.38 (2H,
d, J¼8.4 Hz), 7.30 (1H, dd, J¼5.2, 1.6 Hz), 7.20 (2H, d, J¼8.4 Hz), 6.96
(2H, m), 4.07 (1H, d, J¼15.2 Hz, Hb-4), 3.89 (1H, d, J¼15.2 Hz, Ha-4),
2.36 (3H, s, Me); dC (100 MHz, CDCl3) 175. 2 (q, J¼34.3 Hz, C]O),
171.8 (C2), 148.0, 140.6, 138.5, 132.4, 130.0, 129.5, 129.0, 128.2
(2CH]), 126.9 (2CH]), 126.7, 126.2 (2CH]), 125.5 (2CH]), 117.0
3.4.21. 2,2,2-Trifluoro-1-[5-(4-fluorophenyl)-2-phenyl-5-(thiophen-
2-yl)-4,5-dihydrofuran-3-yl]ethanone (3u). Yield 88% (368 mg) as
yellow oil. Found: C, 62.86; H, 3.49; S, 7.43 C22H14F4O2S requires C,
63.15; H, 3.37; S, 7.66%; Rf (20% EtOAc/hexane) 0.44; nmax (KBr disc)
3063, 2980, 1685 (C]O), 1575 (C]C), 1199 (CF3), 1138 (CeOeC),
904, 764, 700; dH (400 MHz, CDCl3) 7.92 (2H, dd, J¼8.8, 1.2 Hz), 7.55
(1H, t, J¼7.6 Hz), 7.50e7.45 (4H, m), 7.35 (1H, dd, J¼4.8, 2.0 Hz), 7.11
(2H, t, J¼8.8 Hz), 7.00 (2H, m), 4.13 (1H, d, J¼14.8 Hz, Hb-4), 3.89
(1H, d, J¼14.8 Hz, Ha-4); dC (100 MHz, CDCl3) 175.0 (q,
1
2JCeF¼35.4 Hz, C]O), 171.4 (C2), 162.6 (d, JCeF¼246.2 Hz, Cipso),
4
139.1 (d, JCeF¼3.0 Hz), 132.2, 129.7, 128.7, 128.6, 128.0, 127.3 (d,

M. Yılmaz / Tetrahedron 67 (2011) 8255e8263
8263
3JCeF¼8.4 Hz, 2CH]), 126.8 (2CH]), 126.6, 126.0 (2CH]), 116.8 (q,
Oxford, 2004; (f) Isanbor, C.; O’Hagan, D. J. Fluorine Chem. 2006, 127, 303e319;
(g) Ismail, F. M. D. J. Fluorine Chem. 2002, 118, 27e33.
2
1JCeF¼290.3 Hz, CF3), 115.5 (d, JCeF¼21.4 Hz, 2CH]), 104.8 (C3),
2. (a) Tozer, M. J.; Herpin, T. F. Tetrahedron 1996, 52, 8619e8683; (b) Altenburger,
J. M.; Schirlin, D. Tetrahedron Lett. 1991, 32, 7255e7258; (c) Brady, K.; Wei, A. Z.;
Ringe, D.; Abeles, R. H. Biochemistry 1990, 29, 7600e7607; (d) Tanaka, T.; Ka-
wase, M.; Tani, S. Life Sci. 2003, 73, 2985e2990; (e) Spengler, G.; Molnar, A.;
Klausz, G.; Mandi, Y.; Kawase, M.; Motohashi, N.; Molnar, J. Int. J. Antimicrob.
Agents 2004, 23, 631e633; (f) Frey, R. R.; Wada, C. K.; Garland, R. B.; Curtin, M.
L.; Michaelides, M. R. Bioorg. Med. Chem. Lett. 2002, 12, 3443e3447.
90.9 (C5), 44.8 (q, 4JCeF¼3.9 Hz, C4); dF (376 MHz, CDCl3) ꢀ115.1 (1F,
m, arom.CF), ꢀ77.1 (3F, s, CF3); LC/MS, m/z (ESIþ) 419 (MHþ, 100%).
3.4.22. 2,2,2-Trifluoro-1-[5-(4-fluorophenyl)-2-methyl-5-(thiophen-
2-yl)-4,5-dihydrofuran-3-yl]ethanone (3v). Yield 70% (249 mg) as
colorless oil. Found: C, 57.55; H, 3.45; S, 9.24 C17H12F4O2S requires C,
57.30; H, 3.39; S, 9.00%; Rf (20% EtOAc/hexane) 0.51; nmax (KBr disc)
3053, 2934,1679 (C]O),1571 (C]C),1330,1195 (CF3),1145 (CeOeC),
985, 906, 746, 702; dH (400 MHz, CDCl3) 7.41 (2H, dd, J¼9.2, 5.2 Hz),
7.31 (1H, dd, J¼5.2, 1.2 Hz), 7.08 (2H, t, J¼8.4 Hz), 6.97 (1H, dd, J¼6.0,
4.8 Hz), 6.90 (1H, dd, J¼3.2,1.2 Hz), 3.91 (1H, d, J¼14.8 Hz, Hb-4), 3.65
(1H,d,J¼14.8 Hz, Ha-4), 2.46(3H, s,Me);dC (100 MHz,CDCl3)176.2(q,
2JCeF¼35.0 Hz, C]O),175.4 (C2),162.5(d,1JCeF¼246.0 Hz, Cipso),147.5,
3. (a) Kawase, M.; Harada, H.; Saito, S.; Cui, J.; Tani, S. Bioorg. Med. Chem. Lett. 1999,
9, 193e194; (b) Kawase, M.; Motohashi, N.; Sakagami, H.; Kanamoto, T.; Na-
ꢀ
kashima, H.; Ferenczy, L.; Wolfard, K.; Miskolci, C.; Molnar, J. Int. J. Antimicrob.
ꢀ
Agents 2001, 18, 161e165; (c) Molnar, A.; Wolfart, K.; Kawase, M.; Motohashi, N.;
ꢀ
Molnar, J. In Vivo 2004, 18, 505e507.
4. Kawase, M.; Sakagami, H.; Kusama, K.; Motohashi, N.; Saito, S. Bioorg. Med.
Chem. Lett. 1999, 9, 3113e3118.
5. (a) Dean, F. M. Advences in Heterocyclic Chemistry; Academic: New York, NY,
1982; Vol. 30; 167e238; (b) Dean, F. M.; Sargent, M. V. Comprehensive Het-
erocyclic Chemistry; Pergamon: New York, NY, 1984; Vol. 4, Part 3, 531e598; (c)
Elbe, H.-L.; Kunisch, F.; Bielefeldt, D.; Tiemann, R.; Stenzel, K.; Dutzmann, S.;
Kugler, M.; Schrage, H. U.S. Patent 6,107,336, Aug. 22, 2000. (d) Logoglu, E.;
Yılmaz, M.; Katircioglu, H.; Yakut, M.; Mercan, S. Med. Chem. Res. 2010, 19,
490e497; (e) Miski, M.; Jakupovic, J. Phytochemistry 1990, 29, 1995e1998; (f)
Zdero, C.; Bohlman, F.; King, R. M.; Robinson, H. Phytochemistry 1986, 25,
509e516; (g) Hofman, G.; Jhonson, R. K. J. Nat. Prod. 1993, 56, 1500e1505.
6. (a) Alagoz, O.; Yılmaz, M.; Pekel, A. T. Synth. Commun. 2006, 36, 1005e1013; (b)
Yılmaz, M.; Pekel, A. T. Synth. Commun. 2001, 31, 3871e3876; (c) Yılmaz, M.;
Pekel, A. T. Synth. Commun. 2001, 31, 2189e2194; (d) Yılmaz, M.; Bicer, E.; Pekel,
A. T. Turk. J. Chem. 2005, 29, 579e587; (e) Yılmaz, M.; Yakut, M.; Pekel, A. T.
Synth. Commun. 2008, 38, 914e927; (f) Yılmaz, M.; Uzunalioglu, N.; Pekel, A. T.
Tetrahedron 2005, 61, 8860e8867; (g) Burgaz, E. V.; Yilmaz, M.; Pekel, A. T.;
Oktemer, A. Tetrahedron 2007, 63, 7229e7239; (h) Yılmaz, M.; Uzunalioglu, N.;
Yakut, M.; Pekel, A. T. Turk. J. Chem. 2008, 32, 411e422; (i) Yılmaz, M.; Pekel, A.
T. J. Fluorine Chem. 2005, 126, 401e406.
3
139.3, 127.2 (d, JCeF¼8.4 Hz, 2CH]), 126.8, 126.6, 126.0, 116.6 (q,
1JCeF¼289.6 Hz, CF3), 115.4 (d, 2JCeF¼21.3 Hz, 2CH]), 105.4 (C3), 91.7
(C5), 43.8(C4),15.9(Me);dF (376 MHz,CDCl3)ꢀ112.6(1F, m, arom.CF),
ꢀ77.0 (3F, s, CF3); LC/MS, m/z (ESIþ) 357 (MHþ, 100%).
3.4.23. [5-Methyl-5-(thiophen-2-yl)-2-(trifluoromethyl)-4,5-
dihydrofuran-3-yl](phenyl)methanone (4a). Yield 15% (51 mg) as
yellow oil. Found: C, 60.66; H, 3.54; S, 9.24 C17H13F3O2S requires C,
60.35; H, 3.87; S, 9.48%; Rf (20% EtOAc/hexane) 0.35; nmax (KBr disc)
3073, 2936, 2861, 1664 (C]O), 1531 (C]C), 1203 (CF3), 1138
(CeOeC), 758, 700; dH (400 MHz, CDCl3) 7.81 (2H, dd, J¼8.0,1.6 Hz),
7.59 (1H, tt, J¼7.6, 1.6 Hz), 7.46 (2H, t, J¼7.6 Hz), 7.32 (1H, dd, J¼5.2,
1.6 Hz), 7.10 (1H, dd, J¼4.0, 1.6 Hz), 7.02 (1H, dd, J¼4.8, 4.0 Hz), 3.55
7. (a) Citterio, A.; Santi, R.; Fiorani, T.; Strologo, S. J. Org. Chem. 1989, 54,
2703e2712; (b) Citterio, A.; Fancelli, D.; Finzi, C.; Pesce, L. J. Org. Chem. 1989, 54,
2713e2718; (c) Mellor, J. M.; Mohammed, S. Tetrahedron Lett. 1991, 32,
7111e7114; (d) Mellor, J. M.; Mohammed, S. Tetrahedron 1993, 49, 7547e7556;
(e) Nishino, H.; Hguyen, V.; Yoshinaga, S.; Kurosawa, K. J. Org. Chem. 1996, 61,
5
(1H, dq, J¼16.0, JHeF¼2.8 Hz, Hb-4), 3.40 (1H, dq, J¼16.0,
5JHeF¼2.8 Hz, Ha-4), 1.97 (3H, s, Me); dC (100 MHz, CDCl3) 192.2
ꢀ
8264e8271; (f) Garzino, F.; Meou, A.; Brun, P. Tetrahedron Lett. 2000, 41,
2
(C]O), 158.6 (q, JCeF¼34.4 Hz, C2), 147.9, 137.9, 133.8, 129.0
9803e9807; (g) Gregory, B.; Parsons, A. F.; Thomas, C. B. Tetrahedron Lett. 2000,
41, 7751e7755; (h) Kajikawa, S.; Nishino, H.; Kurosawa, K. Heterocycles 2001, 54,
171e183; (i) Gregory, B.; Parsons, A. F.; Thomas, C. B. Tetrahedron 2001, 57,
4719e4728; (j) Melikyan, G. G. Synthesis 1993, 833e850; (k) Igbal, J.; Bhatia, B.;
Nayyar, N. K. Chem. Rev. 1994, 94, 519e564; (l) Snider, B. B. Chem. Rev. 1996, 96,
339e363; (m) Wang, G.-W.; Dong, Y.-W.; Wu, P.; Yuan, T.-T.; Shen, Y.-B. J. Org.
Chem. 2008, 73, 7088e7095; (n) Pan, X.-Q.; Zou, J.-P.; Zhang, W. Mol Diversity
2009, 13, 421e438; (o) Demir, A. S.; Emrullahoglu, M. Curr. Org. Synth. 2007, 4,
223e237; (p) Yilmaz, E. V. B.; Yilmaz, M.; Oktemer, A. ARKIVOC 2011, ii,
363e376.
8. (a) Baciocchi, E.; Ruzziconi, R. Synth. Commun. 1988, 18, 1841e1846; (b) Nair, V.;
Mathew, J.; Radhakrishnan, K. V. J. Chem. Soc., Perkin Trans. 1 1996, 1487e1492;
(c) Kobayashi, K.; Sakashita, K.; Akamatsu, H.; Tanaka, K.; Uchida, M.; Uneda, T.;
Kitamura, T.; Morikawa, O.; Konishi, H. Heterocycles 1999, 51, 2881e2892; (d)
Lee, Y. R.; Kim, B. S.; Kim, D. H. Tetrahedron 2000, 56, 8845e8853; (e) Nair, V.;
Treesa, P. M.; Maliakal, D.; Rath, N. P. Tetrahedron 2001, 57, 7705e7710; (f)
Tseng, C.-H.; Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2002, 58, 7625e7633; (g) Liao,
Y.-J.; Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2003, 59, 3511e3520; (h) Kobayashi,
K.; Nagase, K.; Morikawa, O.; Konishi, H. Heterocycles 2003, 60, 939e946; (i)
Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2004, 60, 1841e1847; (j) Nair, V.; Deepthi,
A. Chem. Rev. C 2007, 107, 1862e1891; (k) Nair, V.; Mohanan, K.; Suja, T. D.;
Suresh, E. Tetrahedron Lett. 2006, 47, 2803e2806; (l) Bahrami, K.; Khodaei, M.
M.; Naali, F. J. Org. Chem. 2008, 73, 6835e6837.
(2CH]), 128.8, 127.2, 125.6 (2CH]), 123.9, 117.1 (q, 1JCeF¼290.1 Hz,
CF3), 106.3 (C3), 88.5 (C5), 48.4 (C4), 28.9 (Me); dF (376 MHz, CDCl3)
ꢀ74.0 (s, CF3); LC/MS, m/z (ESIþ) 339 (MHþ, 100%).
3.4.24. 5-Methyl-3-(naphthalen-2-ylcarbonyl)-5-(thiophen-2-yl)-2-
(trifluoromethyl)tetrahydrofuran-2-yl acetate (4b). Yield 11% (43 mg)
as yellow oil. Found: C, 64.76; H, 3.67; S, 8.53 C21H15F3O2S requires C,
64.94; H, 3.89; S, 8.26%; Rf (20% EtOAc/hexane) 0.40; nmax (KBr disc)
3061, 2976, 1683 (C]O), 1583 (C]C), 1554, 1211 (CF3), 1138
(CeOeC), 758, 696; dH (400 MHz, CDCl3) 8.27 (1H, s), 7.91e7.87 (4H,
m), 7.62 (1H, td, J¼6.8, 1.6 Hz), 7.56 (1H, td, J¼6.8, 1.6 Hz), 7.36 (1H,
dd, J¼4.8, 1.2 Hz), 7.14 (1H, dd, J¼3.6, 1.2 Hz), 7.05 (1H, dd, J¼5.2,
5
3.6 Hz), 3.57 (1H, dq, J¼16.0, JHeF¼2.1 Hz, Hb-4), 3.46 (1H, dq,
5
J¼16.0, JHeF¼2.1 Hz, Ha-4), 2.01 (3H, s, Me); dC (100 MHz, CDCl3)
2
190.8 (C]O), 148.1, 144.4 (q, JCeF¼38.8 Hz, C2), 136.0, 135.2, 132.5,
131.6, 129.9, 129.1, 128.9, 128.1, 127.2, 127.1, 125.6, 124.2, 123.9, 115.9
(q, 1JCeF¼288.4 Hz, CF3), 103.3 (C3), 88.6 (C5), 48.6 (C4), 28.9 (Me); dF
(376 MHz, CDCl3) ꢀ76.4 (s, CF3); LC/MS, m/z (ESIþ) 389 (MHþ, 100%).
9. (a) Manfredinia, S.; Guarneria, M.; Simonia, D.; Granab, E.; Bosellib, C.; Zontab,
F.; Ferianic, A.; Gaviraghic, G.; Tosonc, G. Eur. J. Med. Chem. 1994, 29, 153e161;
(b) Ward, W. J., Jr.; McEwen, W. E. J. Org. Chem. 1990, 55, 493e500; (c) Baker, R.;
Sims, R. J. Synthesis 1981, 117.
Acknowledgements
10. (a) Hajos, Z. G.; Wachter, M. P.; Werblood, H. M. Synth. Commun. 1989, 19,
ꢁ ꢀ
3295e3300; (b) Karminski-Zamola, G.; Jakopcic, K. J. Heterocycl. Chem. 1981, 18,
193e196.
The author is grateful to the Kocaeli University (BAP 2008/28)
11. (a) Fry, A. J.; Allukian, M.; Williams, A. D. Tetrahedron 2002, 58, 4411e4416; (b)
Maccarone, E.; Mamo, A.; Perrini, G.; Torre, M. J. Chem. Soc., Perkin Trans. 2 1981,
324e326.
Science Research Foundations for financial support.
12. (a) Lozac’h, N.; Teste, J. C. R. Chim. 1952, 234, 1891e1893; (b) Skuballa, W.;
References and notes
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