Synthesis of fluoroacylated 4,5-dihydrofurans and fluoroalkylated tetrahydrofurans by the radical cyclization using manganese(III) acetate. Part II

Article abstract of DOI:10.1016/j.jfluchem.2011.06.023

Manganese(III) acetate-based radical cyclizations of various fluorinated 1,3-dicarbonyl compounds with alkenes produced 3-fluoroacylated 4,5-dihydrofurans and 2-acetyloxy-2-fluoroalkylated tetrahydrofurans in good yields. Mechanism was proposed for the fo

Full text of DOI:10.1016/j.jfluchem.2011.06.023

Journal of Fluorine Chemistry 132 (2011) 628–635
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of fluoroacylated 4,5-dihydrofurans and fluoroalkylated
tetrahydrofurans by the radical cyclization using manganese(III) acetate. Part II
b
Mehmet Yılmaz a, , A. Tarık Pekel
*
a Department of Chemistry, Faculty of Arts and Sciences, Kocaeli University, 41380 Umuttepe, Kocaeli, Turkey
b Ankara University, Science Faculty, Department of Chemistry 06100 Tandogan, Ankara, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history:
Manganese(III) acetate-based radical cyclizations of various fluorinated 1,3-dicarbonyl compounds with
alkenes produced 3-fluoroacylated 4,5-dihydrofurans and 2-acetyloxy-2-fluoroalkylated tetrahydrofur-
ans in good yields. Mechanism was proposed for the formation of all compounds. The radical cyclization
of fluorinated 1,3-dicarbonyls showed to form different cyclized products depending on the structure of
alkenes and enol forms of 1,3-dicarbonyls.
Received 11 February 2011
Received in revised form 12 June 2011
Accepted 17 June 2011
Available online 24 June 2011
ß 2011 Elsevier B.V. All rights reserved.
Keywords:
Manganese(III) acetate
Radical cyclization
Fluorinated 1,3-dicarbonyl
Trifluoromethyl ketone
1. Introduction
studied the radical cyclization of 1,3-dicarbonyl compounds and 3-
oxopropanenitriles with alkenes, alkynes, unsaturated amides and
The use of fluorine atom in the synthesis of organic compounds
is developing due to their unique physico-chemical and biological
properties. Thus, fluorinated organic compounds containing
trifluoromethyl have received considerable attention in the
medicinal and agricultural chemistry [1]. Many of trifluoromethyl
ketones have been found to show enzyme inhibition [2],
antimicrobial activity [3] and some trifluoromethyl ketones have
been demonstrated as cytotoxic agents against human tumor cell
[4].
Traditionally, methods for the synthesis of fluorine containing
organic compounds are direct fluorination and fluoroalkylation
[5]. One possible approach would be the cyclization of a suitable
fluorinated 1,3-dicarbonyl compounds with unsaturated systems
mediated by transition metal salts (Mn+3, Ce+4, Ag+, etc.) [6].
These metal salts such as manganese(III) acetate [7] and
cerium(IV) ammonium nitrate [8] are very important radical
oxidants in the organic synthesis for the construction of carbon–
carbon bonds.
dienes using manganese(III) acetate, resulting the formation
of many dihydrofuran derivatives [10]. Recently, we obtained
2,3-dihydro-4H-furo[3,2-c]chromen-4-ones
and
2,3-dihydro-
naphtho [2,3-b]furan-4,9-diones by the radical cyclization of 4-
hydroxycoumarin and 2-hydroxy-1,4-naphtoquinone, respectively
[10e]. Previously, we described the synthesis of 3-trifluoroacetyl-4,5-
dihydrofurans and 3-[dihydrofuran-2(3H)-ylidene]-1,1,1-trifluor-
oacetones by the treatment of trifluoromethyl-1,3-dicarbonyl
compounds with alkenes [10i]. In this paper, we studied radical
cyclization of basic and available various tri, and hepta fluorinated
1,3-dicarbonyl compounds 1a–g with conjugated alkenes 2a–f
using manganese(III) acetate. As a result of these reactions, we
obtained fluoroacylated 4,5-dihydrofurans and fluoroalkylated
tetrahydrofurans depending on the enol form of 1,3-dicarbonyls
and structure of alkenes.
2. Results and discussions
Dihydrofurans are significant class of compounds since they
show a wide range of biological activities and form the basic
structure of many natural compounds [9]. Our research group have
All fluorinated-1,3-dicarbonyls 1a–f are available commercial
products and were used in highest purity. The conjugated alkenes
2a–c were prepared by dehydration from the carbinole formed
from Grignard reaction of arylmagnesium bromide and suitable
carbonyl compounds. Radical reactions were performed at
1.2:1:2.5 molar ratio (1:2:Mn(OAc)3) under a nitrogen atmosphere
in AcOH. All compounds purified by column chromatography or
* Corresponding author. Tel.: +90 2623032058; fax: +90 2623032003.
E-mail address: mehmet.yilmaz@kocaeli.edu.tr (M. Yılmaz).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.06.023

M. Yılmaz, A.T. Pekel / Journal of Fluorine Chemistry 132 (2011) 628–635
629
preparative TLC were characterized by IR, 1H, 13C, 19F NMR, mass
spectra and microanalysis.
177 ppm in 13C NMR, the carbonyl carbon of compound 3d gives
singlet at 194 ppm. On the other hand, while C-2 carbon of 3d gives
quartet (2JC-F = 34.4 Hz) at 150 ppm, C-2 of 3c gives singlet at
178 ppm. On the other side, only 3-trifluoroacetyl-4,5-dihydrofur-
ans 3e–g were isolated from the treatment of 1b–d with 2b in good
yields. The radical cyclization of 4,4,4-trifluoro-1-thien-2-ylbu-
tane-1,3-dione 1d with 2c gave 3-trifluoroacetyl-4,5-dihydrofuran
3 h (83%) in good yield.
As seen in Table 1, the radical cyclizations of 1a and 1b with 2a
afforded 3-trifluoroacetyl-4,5-dihydrofurans 3a (72%) and 3b
(95%) in high yields. The compounds of 3-trifluoroacetyl-4,5-
dihydrofuran 3c (34%) and 2-trifluoromethyl-4,5-dihydrofuran 3d
(15%) obtained from the reaction of 1a with 1-phenyl-1-
cyclopentene (2b) were differentiated by means of the chemical
shifts of carbonyl carbons of these compounds in 13C NMR spectra.
Whereas the carbonyl carbon of 3c gives quartet (2JC-F = 34.8 Hz) at
We obtained interesting results from the reactions of 2c with
fluorinated 1,3-dicarbonyl compounds (1a–c, 1e, 1f) in Table 2.
Table 1
Radical cyclizations of 1a–d with the alkenes 2a–c.
Entry
1,3-Dicarbonyl
Alkene
Product
Yielda (%)
1
3a, 72
2
2a
3b, 95
3
3c, 34
3d, 15
4
2b
3e, 57
5
6
2b
2b
3f, 60
3g, 64
7
3h, 83
3i (34%)
a
Isolated yield based on the amount of the alkene used.

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Table 2
Radical cyclization of fluorinated 1,3-dicarbonyl compounds with 2c.
Entry 1,3-Dicarbonyl
Alkene
Product and yielda (%)
1
3i (34%)
2
2c
3
2c
4
2c
5
2c
a
Isolated yield based on the amount of alkene used.
While the reaction of 2,4-pentanedione with 2c was reported to
produce 4,5-dihydrofuran as single product [8b], treatment of 1a
with 2c formed 3-trifluoroacetyl-4,5-dihydrofuran 3i and hex-
ahydrobenzofuran-2(3H)-ylidenepropen-2-one 4 (Table 2, entry
1). Since 13C NMR spectrum of 4 showed a quartet at 181.1 ppm
(2JC-F = 33.8 Hz) for carbonyl carbon, the CF3 group is adjacent to
the carbonyl group. Moreover, COSY spectrum showed that H-3
protons couple with olefinic proton.
3-Fluoroacylated-4,5-dihydrofurans 3j–m formed by the
cyclization of the corresponding enol form of 1,3-dicarbonyls
(1b, 1c, 1e, 1f) were obtained along with in situ 2-acetyloxy-2-
fluoroalkyl-tetrahydrofurans 5a–d which are HOAc adducts of 2-
fluoroalkylated 4,5-dihydrofurans formed by the cyclization of
the other enol form of the 1,3-dicarbonyls. Among these
compounds, 5c (dr = 73:27) and 5d (dr = 80:20) were isolated
as diastereomeric mixtures and the ratio was determined by 1H
NMR. Although most of the obtained products have two or more
stereocenters, all of the compounds were obtained as one isomer
except for 5c and 5d.
interaction of enol form of the 1,3-dicarbonyl 1a–f with
manganese(III) acetate produces Mn(III)-enolate complex A.
When the R1 is methyl group, the elimination of a methyl proton
from Mn(III)-enolate complex leads to the formation of Mn(III)-
dienolate complex B. While Mn+3 is reduced to Mn+2, a terminal
radical carbon is formed on this structure. The radical
intermediate D formed by the addition of an electron from 2c
to the terminal radical is oxidized to carbocation E by Mn(OAc)3
and cyclization of E gives the compound 4. Similarly, a radical-
carbon intermediate product F is formed while Mn+3 is reduced
to Mn+2 on the structure A. Addition of the radical-carbon to
alkene followed oxidation by Mn(OAc)3 gave intermediate
carbocation G. Fluoroacylated 4,5-dihydrofurans H are formed
by the cyclization of carbocation intermediate M the enol form
of the G. 2-Acetyloxy-2-fluoroalkylated tetrahydrofurans
L
are formed via the cyclization of hemiacetalic structure K
obtained from addition of HOAc to the carbonyl group of G.
Moreover, fluoroalkylated 4,5-dihydrofurans
J are formed
either by the cyclization of carbocation intermediate I, the
other enol form of G, or a pyrolytic elimination of HOAc from
compound L.
The mechanism proposed for the formation of all compounds
is explained in Scheme 1. According to this mechanism, the

M. Yılmaz, A.T. Pekel / Journal of Fluorine Chemistry 132 (2011) 628–635
631
Scheme 1. Mechanism for the radical cyclizations of fluorinated 1,3-dicarbonyls with alkene.
3. Conclusion
4. Experimental
In conclusion, the radical cyclizations of various fluorinated
1,3-dicarbonyl compounds with conjugated alkenes mediated
by Mn(OAc)3 were performed in this study. These results show
quite different from that of nonflourinated 1,3-dicarbonyl
compounds in many ways. We think that this difference
arises from fluorine atoms’ changing tautomeric properties of
1,3-dicarbonyl compounds. Enol forms of 1,3-dicarbonyls play
an important role in variety of products formed in radical
cyclization of alkenes.
This study introduces that fluorinated 1,3-dicarbonyl com-
pounds can be used effectively in the radical cyclizations for
synthesis of various fluorinated organic compounds such as
fluoroalkylated tetrahydrofurans and fluoroacylated 4,5-dihydro-
furans.
4.1. General
Melting points were determined on a electrotermal capillary
melting point apparatus. IR spectra (KBr disc, CHCl3) were
obtained with a Matson 1000 FT-IR in the 400–4000 cmÀ1 range
with 4 cmÀ1 resolution. 1H NMR (400 MHz), 19F NMR (376 MHz)
and 13C NMR (100 MHz) spectra were recorded on a Bruker
Avance DPX-400 MHz and Varian Mercury-400 High perfor-
mance Digital FT-NMR spectrophotometers. The mass spectra
were measured on a Agilent 1100 MSD LC/MS (APCI, 100 eV), a
Shimadzu GC-17A/GC-MS-QP5000 (EI, 70 eV) and a Waters 2695
Alliance Micromass ZQ (ESI+) LC/MS spectrophotometer. Ele-
mental analyses were performed on
instrument.
a Leco 932 CHNS-O

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M. Yılmaz, A.T. Pekel / Journal of Fluorine Chemistry 132 (2011) 628–635
Thin layer chromatography (TLC) was performed on Merck
aluminium-packed silica gel plates. Purification of products was
performed by column chromatography on silica gel (Merck silica
F = 290.9 Hz, –CF3), 112.0 (C-3), 103.6 (C-6a), 53.7 (CH3), 42.8 (C-6),
36.4 (C-3a), 25.1 (C-4), 16.4 (C-5); 19F NMR (376 MHz, CDCl3):
d
À66.3(s, CF3); GC–MS (EI, 70 eV), m/z (%):297(MH+, 20.98), 296 (M+,
50.35), 281 (M+–CH3, 1.78), 278 (MH+–F, 7.21), 227 (M+–CF3, 13.29),
199 (M+–CF3CO, 6.38), 105 (PhCO+, 43.71), 91 (PhCH2+, 12.94), 77
(C6H5+, 35.84), 69 (CF3+, 13.99), 43 (CH3CO+, 100.00). Anal. Calcd for
C16H15F3O2: C, 64.86; H 5.10. Found: C, 64.75; H, 5.21.
gel 60, 40–63
mm) or preparative TLC on silica gel of Merck (PF254–
366nm). All trifluoromethyl-1,3-dicarbonyl compounds, solvents
and reagents were purchased highest purity.
4.2. General procedure for synthesis of 4,5-dihydrodurans and
tetrahydrofurans
1-[2-(Trifluoromethyl)-6a-phenyl-4,5,6,6a-tetrahydro-3aH-
cyclopenta[b]furan-3-yl]ethanone (3d). Yield 15% (111 mg) as
colourless oil. ymax (KBr disc) 2961, 2872, 1656 (C55O), 1581 (C55C),
A solution of manganese(III) acetate dihydrate(5 mmol, 1.35 g)in
20 mLinglacial acetic acid was heated under nitrogenatmosphere at
80 8C until it dissolved. After Mn(OAc)3 dissolved completely, the
solution was cooled downto60 8C. A solution of trifluoromethyl-1,3-
dicarbonyl compound (2.5 mmol) and alkene (2 mmol) in 5 mL
aceticacidwasadded tothismixtureand thetemperaturewasraised
to 80 8C. The reaction was complete when the dark brown colour of
the solution disappeared. Acetic acid was evaporated under reduced
pressure. Water was added to the residue and extraction was
performed with CHCl3 (3 Â 20 mL). The combined organic extracts
were neutralized with satd. NaHCO3 solution, and dried over
anhydrous Na2SO4 and evaporated. Crude products were purified
by column chromatography or preparative TLC (20 cm  20 cm
plates, 2 mm thickness) using n-hexane/EtOAc (5:1) as eluent.
1148 (C–F), 1151 (C–O–C), 760, 700; 1H NMR (400 MHz, CDCl3):
d
7.37 (5H, m, arom. H), 3.84 (1H, dt, J = 8.8, 5JH-F = 1.9 Hz, 3a-H), 2.44
(1H, dd, J = 14.0, 5.9 Hz), 2.35 (3H, s, CH3), 2.01 (2H, m), 1.95 (2H,
m), 1.80 (1H, m); 13C NMR (100 MHz, CDCl3):
d
194.6 (C55O), 150.0
2
(q, JC-F = 34.4 Hz, C-2), 144.0, 129.8, 129.0, 125.1, 121.6 (C-3),
119.5 (q, 1JC-F = 273.8 Hz, –CF3), 101.8 (C-6a), 57.5 (CH3), 44.1 (C-6),
4
30.3 (q, JC-F = 3.5 Hz, C-3a), 35.0 (C-4), 25.4 (C-5); 19F NMR
(376 MHz, CDCl3):
d
À63.5 (s, CF3); GC–MS (EI, 70 eV), m/z (%): 297
(MH+, 3.78), 296 (M+, 16.35), 278 (MH+–F, 13.17), 227 (M+–CF3,
32.52), 199 (M+–CF3CO, 26.67), 185 (MH+–CF3CO–CH3, 33.03), 142
(M+–CF3CO–C3H5O, 25.07), 91 (PhCH2+, 21.78), 77 (C6H5+, 35.29),
43 (CH3CO+, 100.00). Anal. Calcd for C16H15F3O2: C, 64.86; H 5.10.
Found: C, 64.73; H, 5.32.
2,2,2-Trifluoro-1-[2-(2-furyl)-6a-phenyl-4,5,6,6a-tetrahydro-
3aH-cyclopenta[b]furan-3-yl]ethanone (3e). Yield 57% (496 mg) as
yellow oil. ymax (KBr disc) 3027, 2925, 1711 (C55O), 1698 (C55C),
1592, 1221 (C–F), 926 (C–O–C), 749, 693; 1H NMR (400 MHz,
4.3. Spectroscopic data of fluoroacylated dihydrofurans and
fluoroalkylated tetrahydrofurans
CDCl3):
d 8.36 (1H, d, J = 3.6 Hz), 7.69 (1H, dd, J = 1.6, 0.8 Hz), 7.48
2,2,2-Trifluoro-1-[2-methyl-5,5-bis(4-methylphenyl)-4,5-dihy-
drofuran-3-yl]ethanone (3a). Yield 72% (648 mg) as colourless oil.
(2H, d, J = 8.0 Hz), 7.39 (2H, t, J = 7.2 Hz), 7.32 (1H, tt, J = 7.6, 1.2 Hz),
6.63 (1H, dd, J = 4.0, 1.6 Hz), 3.97 (1H, d, J = 8.8 Hz, 4-H), 2.55 (1H,
dd, J = 14.4, 6.0 Hz, 6a-H), 2.27–2.15 (2H, m), 2.03–1.94 (2H, m),
y
max (KBr disc) 1687 (C55O), 1581 (C55C), 1201 (C–F), 1134 (C–O–C),
906, 816; 1H NMR (400 MHz, CDCl3):
7.35 (4H, dt, J = 8.3, 1.9 Hz,
arom. H), 7.28 (4H, d, J = 8.2 Hz, arom. H), 3.87 (2H, s, 4-H), 2.59 (3H,
s, CH3), 2.46 (6H, s, CH3); 13C NMR (100 MHz, CDCl3): 177.7 (q, 2JC-
d
1.84 (1H, m); 13C NMR (100 MHz, CDCl3): 174.4 (q, 2JC-F = 34.3 Hz,
d
C55O), 161.8 (C-2), 146.8, 144.3, 142.7, 128.8, 128.2, 124.6, 122.4,
121.8–113.1 (q, 1JC-F = 289.6 Hz, –CF3), 112.8, 109.4 (C-3), 102.5 (C-
d
F = 35.1 Hz, C55O), 177.4 (C-2), 142.3, 139.1, 130.4, 126.7, 119.3 (q,
1JC-F = 290.9 Hz, –CF3), 106.6 (C-3), 95.7 (C-5), 42.8 (q, 4JC-F = 1.05 Hz,
6a), 53.6, 42.1, 36.9, 25.0; 19F NMR (376 MHz, CDCl3):
d
À74.6 (s,
CF3); LC–MS (ESI+), m/z (%) 349 (MH+, 100%). Anal. Calcd for
C-4), 21.5, 16.5; 19F NMR (376 MHz, CDCl3):
d
À77.0 (s, CF3); GC–MS
C19H15F3O3: C, 65.52; H, 4.34. Found: C, 65.65; H, 4.52.
(EI, 70 eV), m/z (%): 360 (M+, 23.38), 317 (M+ –CF3CO, 16.05), 291
2,2,2-Trifluoro-1-(2,6a-diphenyl-4,5,6,6a-tetrahydro-3aH-
(M+–CF3, 13.36), 248 (M+–CH3CO–CF3, 42.61), 220 (M+–CF3CO–
cyclopenta[b]furan-3-yl)-ethanone (3f). Yield 60% (537 mg) as
colourless oil. max (KBr disc) 2963, 2870, 1681 (C55O), 1583 (C55C),
1205 (C–F), 1140 (C–O–C), 760, 696; 1H NMR (400 MHz, CDCl3):
CH3CO, 36.75), 202 (M+–F2–CH3CO–C6H5, 35.32), 91 (PhCH2
,
y
+
28.08), 77 (C6H5+, 23.21), 69 (CF3 , 5.25), 43 (CH3CO+, 100.00). Anal.
d
+
Calcd for C21H19F3O2: C, 69.99; H, 5.31. Found: C, 70.23; H, 5.22.
7.81 (2H, dt, J = 7.3, 1.3 Hz), 7.55–7.37 (8H, m, arom. H), 4.01 (1H, d,
J = 8.6 Hz, 3a-H), 2.51 (1H, dd, J = 13.9, 5.8 Hz), 2.27–2.15 (2H, m),
2.11 (1H, m), 2.01 (1H, m), 1.88 (1H, m); 13C NMR (100 MHz,
´
2,2,2-Trifluoro-1-[5,5-bis(4-methylphenyl)-4,5-dihydro-2,2-
bifuran-3-yl]-ethanone (3b). Yield 95% (978 mg) as pale yellow oil.
ymax (KBr disc) 3028, 2924, 1675 (C55O), 1569 (C55C), 1537, 1219
(C–F), 1180 (C–O–C), 918, 849, 818, 764; 1H NMR (400 MHz,
CDCl3):
d
177.1 (q, 2JC-F = 34.7 Hz, C55O), 174.3 (C-2), 143.6, 132.6,
130.4, 130.0, 129.5, 128.8, 128.7, 125.1, 118.9 (q, 1JC-F = 291.7 Hz, –
CDCl3):
d
8.42 (1H, d, J = 3.7 Hz), 7.72 (1H, d, J = 0.9 Hz), 7.38 (4H, d,
CF3), 111.2, 102.3 (C-3), 54.3 (C-3a), 42.4 (C-6), 36.4 (C-4), 24.8 (C-
J = 8.2 Hz), 7.20 (4H, d, J = 8.1 Hz), 6.65 (1H, dd, J = 3.7, 1.6 Hz), 4.00
5); 19F NMR (376 MHz, CDCl3):
d
À75.3 (s, CF3); GC–MS (EI, 70 eV),
(2H, s, 4-H), 2.36 (6H, s, CH3); 13C NMR (100 MHz, CDCl3):
d
174.5
m/z (%): 359 (MH+, 4.31), 358 (M+, 15.99), 289 (M+–CF3, 7.72), 261
(M+–CF3CO, 2.99), 184 (M+–CF3CO–PhCO, 1.18), 105 (PhCO+,
100.00), 91 (PhCH2+, 7.85), 77 (C6H5+, 67.12), 69 (CF3+, 5.60). Anal.
Calcd for C21H17F3O2: C, 70.38; H, 4.78. Found: C, 70.72; H, 4.63.
2,2,2-Trifluoro-1-(6a-phenyl-2-thien-2yl-4,5,6,6a-tetrahydro-
3aH-cyclopenta[b]furan-3-yl)ethanone (3g). Yield 64% (582 mg) as
2
(q, JC-F = 34.3 Hz, C55O), 161.6 (C-2), 147.5, 145.2, 141.5, 138.7,
1
130.0, 126.4, 123.1, 119.3 (q, JC-F = 291.4 Hz, –CF3), 113.4, 104.2
(C-3), 94.7 (C-5), 42.9 (d, JC-F = 3.2 Hz, C-4), 21.2 (CH3); 19F NMR
(376 MHz, CDCl3):
(MH+, 0.49), 412 (M+, 2.29), 343 (M+–CF3, 1.36), 317 (M+–C5H3O2,
20.28), 315 (M+–CF3, 5.45), 275 (M+–CF3-C4H3O, 8.21), 219 (M+–
CF3CO–C5H3O2, 6.61), 178 (M+–CF3CO–C5H3O2–CH3, 11.43), 95
(C5H3O2+, 100.00), 69 (CF3+, 10.80). Anal. Calcd for C24H19F3O3: C,
69.90; H 4.64. Found: C, 70.06; H, 4.51.
4
d
À76.8 (s, CF3); GC–MS (EI, 70 eV), m/z (%): 413
a yellow solid, m.p. 95–96 8C (Hexane/EtOAc).
(C55O), 1531 (C55C), 1199 (C–F), 1140 (C–O–C), 731, 700; 1H NMR
(400 MHz, CDCl3): 8.65 (1H, dd, J = 4.0, 1.2 Hz), 7.79 (1H, dd,
ymax (KBr disc) 1660
d
J = 5.1, 1.2 Hz), 7.53 (2H, dt, J = 7.1, 1.6 Hz), 7.46 (2H, td, J = 6.2,
1.5 Hz), 7.42 (1H, tt, J = 7.2, 1.4 Hz), 7.31 (1H, dd, J = 5.0, 4.0 Hz),
4.06 (1H, d, J = 8.9 Hz, 3a-H), 2.58 (1H, dd, J = 13.9, 5.8 Hz), 2.26
(1H, m), 2.35 (1H, m), 2.07 (2H, m), 1.92 (1H, m); 13C NMR
2,2,2-Trifluoro-1-(2-methyl-6a-phenyl-4,5,6,6a-tetrahydro-
3aH-cyclopenta[b]furan-3-yl)ethanone (3c). Yield 34% (252 mg) as
colourless oil.
ymax (KBr disc) 2963, 2872, 1679 (C55O), 1571 (C55C),
1199 (C–F), 1140 (C–O–C), 762, 700; 1H NMR (400 MHz, CDCl3):
d
(100 MHz, CDCl3):
d
176.3 (q, JC-F = 34.2 Hz, C55O), 167.9 (C-2),
2
7.33–7.22 (5H, m), 3.72 (1H, d, J = 8.4 Hz, 3a-H), 2.33 (3H, s, CH3),
2.30 (1H, dd, J = 13.9, 5.9 Hz), 1.98 (1H, dd, J = 13.8, 6.2 Hz), 1.84 (2H,
143.9, 136.4, 134.8, 132.0, 129.9, 129.1, 129.0, 125.4, 119.8 (q, 1JC-
F = 291.6 Hz, –CF3), 109.9 (C-3), 102.6 (C-6a), 54.5 (d, 4JC-F = 2.3 Hz,
C-3a), 42.6 (C-6), 37.4 (C-4), 25.4 (C-5); 19F NMR (376 MHz, CDCl3):
À74.2 (s, CF3); GC–MS (EI, 70 eV), m/z (%): 364 (M+, 28.67), 326
m), 1.64 (1H, m); 13C NMR (100 MHz, CDCl3):
d 178.6 (C-2), 177.9 (q,
2JC-F = 34.8 Hz, C55O), 144.1, 129.6, 128.7, 125.4, 117.8 (q, JC-
d
1

M. Yılmaz, A.T. Pekel / Journal of Fluorine Chemistry 132 (2011) 628–635
633
(M+–F2, 21.84), 295 (M+–CF3, 18.69), 258 (M+–PhCO, 20.63), 252
5); 19F NMR (376 MHz, CDCl3):
d
À74.0 (s, CF3); GC–MS (EI, 70 eV),
(M+–CF3-C3H5-C5H3OS, 33.67), 111 (C5H3OS+, 100.00), 105 (PhCO+,
39.0), 83 (C4H3S+, 14.92). Anal. Calcd for C19H15F3O2S: C, 62.63; H,
4.15; S, 8.80. Found: C, 62.82; H, 4.08; S, 8.64.
m/z (%): 373 (MH+, 9.31), 372 (M+, 23.39), 354 (MH+–F, 23.53), 303
(M+–CF3, 19.80), 267 (M+–PhCO+, 100.00), 91 (PhCH2+, 13.53), 77
(C6H5+, 40.39), 69 (CF3+, 24.90). Anal. Calcd for C22H19F3O2: C,
70.96; H 5.14. Found: C, 71.25; H, 5.06.
2,2,2-Trifluoro-1-(7a-phenyl-2-thien-2-yl-3a,4,5,6,7,7a-hexa-
hydro-1-benzofuran-3-yl)ethanone (3h). Yield 83% (784 mg) as a
yellow solid, m.p. 105–107 8C (Hexane/EtOAc). ymax (KBr disc)
2,2,3,3,4,4,4-Heptafluoro-1-[7a-phenyl-2-(2-thienyl)-
3a,4,5,6,7,7a-hexahydro-1-benzofuran-3-yl]butan-1-one
Yield 30% (359 mg) as pale yellow oil. ymax (KBr disc) 3027,
2978, 1691 (C55O), 1643 (C55C), 1235 (C–F), 966 (C–O–C), 748, 693;
1H NMR (400 MHz, CDCl3):
d 8.62 (1H, dd, J = 4.0, 1.2 Hz), 7.72 (1H,
(3l).
1664 (C55O), 1531 (C55C), 1203 (C–O–C), 1138 (C–F), 758, 700; 1
H
NMR (400 MHz, CDCl3): d 8.67 (1H, dd, J = 4.0, 1.1 Hz), 7.76 (1H, dd,
J = 5.0, 1.1 Hz), 7.47 (2H, dt, J = 7.3, 1.5 Hz), 7.37 (2H, td, J = 7.0,
1.9 Hz), 7.28 (3H, m), 3.64 (1H, t, J = 7.2 Hz, 3a-H), 2.45 (1H, dd,
J = 12.6, 4.2 Hz), 2.38 (1H, t, J = 10.8 Hz), 1.68 (2H, m), 1.82 (3H, m),
dd, J = 5.2, 1.2 Hz), 7.41 (2H, d, J = 7.2 Hz), 7.29 (2H, t, J = 7.2 Hz),
7.23 (2H, m), 3.59 (1H, m, 3a-H), 2.41 (1H, dt, J = 15.2, 2.0 Hz), 2.31
1.42 (1H, m); 13C NMR (100 MHz, CDCl3):
d
175.8 (q, 2JC-F = 34.5 Hz,
(1H, m), 1.85 (1H, m), 1.75 (2H, m), 1.59 (1H, m), 1.38 (2H, m); 13
C
C55O), 167.9 (C-2), 146.4, 136.5, 135.0, 133.0, 129.2, 128.7, 128.2,
125.1, 119.8 (q, 1JC-F = 291.4 Hz, –CF3), 113.9 (C-3), 93.2 (C-7a), 45.6
(C-3a), 36.8 (C-7), 31.7 (C-4), 22.4 (C-6), 21.9 (C-5); 19F NMR
NMR (100 MHz, CDCl3): d
176.9 (t, 2JC-F = 25.1 Hz, C55O), 167.4 (C-
2), 142.2, 135.8, 134.3, 132.1, 128.5, 128.2, 127.7, 124.2, 122.0–
113.3 (qt, 1JC-F = 286.5, 2JC-F = 34.2 Hz, –CF2–CF2–CF3), 114.3 (d, 3JC-
F = 3.0 Hz, C-3), 113.0–107.7 (tt, 1JC-F = 266.7, 2JC-F = 31.2 Hz, –CF2–
(376 MHz, CDCl3):
d
À74.0 (s, CF3); GC–MS (EI, 70 eV), m/z (%): 379
(MH+, 2.25), 378 (M+, 32.96), 309 (M+–CF3, 21.77), 266 (M+–CF3-
C3H7, 10.73), 198 (M+–CF3-C5H3OS, 13.67), 111 (C5H3OS+, 53.07),
110 (C5H2OS+, 100.00), 105 (PhCO+, 16.45), 77 (C6H5+, 41.23), 69
(CF3+, 16.34). Anal. Calcd for C20H17F3O2S: C, 63.48, H 4.53, S 8.47.
Found: C 63.35, H 4.48, S 8.36.
CF2–CF3), 111.5–106.2 (tqt, JC-F = 265.2, JC-F = 38.9 Hz, JC-F = not
1
2
3
4
determined –CF2–CF2–CF3), 92.2, 45.5 (d, JC-F = 6.1 Hz, C-4), 36.1,
31.6, 21.9, 21.4; 19F NMR (376 MHz, CDCl3):
3
d
À80.8 (t, JF-
F = 9.4 Hz, 2 F, –CF2CF2CF3), À126.4 (m, 2 F, –CF2CF2CF3), À126.6 (t,
3JF-F = 52.6 Hz, 2 F, –CF2CF2CF3); LC–MS (ESI+), m/z (%): 479 (MH+,
100%). Anal. Calcd for C22H17F7O2S: C, 55.23; H, 3.58; S, 6.70.
Found: C, 55.05; H, 3.32; S, 6.77.
2,2,2-Trifluoro-1-[7a-phenyl-2-(2-naphthyl)-3a,4,5,6,7,7a-hex-
ahydro-1-benzofuran-3-yl]ethanone (3m). Yield 21% (222 mg) as
2,2,2-Trifluoro-1-(2-methyl-7a-phenyl-3a,4,5,6,7,7a-hexahy-
dro-1-benzofuran-3-yl)ethanone (3i). Yield 34% (264 mg) as
colourless oil. ymax (KBr disc) 2937, 2864, 1662 (C55O), 1589
(C55C), 1540, 1253 (C–F), 1171 (C–O–C), 766, 694; 1H NMR
(400 MHz, CDCl3):
J = 6.7 Hz, 3a-H), 2.44 (3H, s, CH3), 2.21 (2H, m), 1.85 (1H, m), 1.71
(2H, m), 1.55 (1H, m), 1.42 (2H, m); 13C NMR (100 MHz, CDCl3):
178.4 (C-2), 177.7 (q, JC-F = 35.1 Hz, C55O), 146.9, 129.5, 128.7,
126.7, 125.1, 119.2 (q, JC-F = 290.7 Hz, –CF3), 115.3, 94.1 (C-7a),
45.7 (C-3a), 35.7 (C-7), 29.4 (C-4), 20.6 (C-6), 16.8 (C-5); 19F NMR
d
7.35 (4H, m), 7.31 (1H, t, J = 4.2 Hz), 3.48 (1H, t,
yellow oil.
y
max (KBr disc) 2962, 1692 (C55O), 1644 (C55C), 1078 (C–
F), 1146 (C–O–C), 786, 692; 1H NMR (400 MHz, CDCl3):
d
8.48 (1H, s),
d
7.90 (1H, dd, J = 7.6, 1.2 Hz), 7.86 (2H, s), 7.85 (1H, dd, J = 7.6, 0.8 Hz),
7.58–7.50 (4H, m), 7.37 (2H, t, J = 7.2 Hz), 7.27 (1H, tt, J = 7.2, 1.2 Hz),
3.67 (1H, t, J = 7.2 Hz, 3a-H), 2.37 (2H, m), 1.91–1.83 (1H, m), 1.77–
1.71 (2H, m), 1.65–1.54 (2H, m), 1.44 (1H, m); 13C NMR (100 MHz,
2
1
2
(376 MHz, CDCl3):
d
À76.5 (s, CF3); GC–MS (EI, 70 eV), m/z (%): 311
CDCl3):
d
175.7 (q, JC-F = 34.3 Hz, C55O), 173.0 (C-2), 145.1, 135.0,
(MH+, 2.28), 310 (M+, 2.31), 267 (M+–CH3CO, 5.72), 213 (M+–
CF3CO, 3.80), 199 (MH+–CH3, –CF3CO+, 8.41), 91 (PhCH2+, 19.86), 77
(C6H5+, 10.92), 69 (CF3+, 10.81), 43 (CH3CO+, 100.00). Anal. Calcd for
132.3, 131.2, 129.0, 128.4, 128.1, 127.8, 127.7, 126.9, 126.7, 125.7,
1
124.3, 121.2–112.5 (q, JC-F = 289.0 Hz, –CF3), 114.2 (C-3), 92.4 (C-
7a), 45.9,35.6,29.8, 20.9, 20.7;19FNMR (376 MHz, CDCl3):
d
À73.8(s,
C17H17F3O2: C, 65.80; H, 5.52. Found: C, 65.82; H 5.38.
CF3); LC–MS (ESI+), m/z (%): 423 (MH+, 100%). Anal. Calcd for
2,2,2-Trifluoro-1-[2-(2-furyl)-7a-phenyl-3a,4,5,6,7,7a-hexahy-
C26H21F3O2: C, 73.92; H 5.01. Found: C, 73.75; H, 4.82.
dro-1-benzofuran-3-yl]ethanone (3j). Yield 29% (263 mg) as pale
yellow oil. ymax (KBr disc) 2940, 2862, 1668 (C55O), 1569 (C55C),
1529, 1263 (C–F), 1201 (C–O–C), 918, 762, 700; 1H NMR (400 MHz,
(3E)-1,1,1-Trifluoro-3-(7a-phenylhexahydro-1-benzofuran-
2(3H)-ylidene)acetone (4). Yield 32% (248 mg) as colourless oily
solid. ymax (KBr disc) 2936, 2861, 1695 (C55O), 1591 (C55C), 1195
CDCl3):
d
8.32 (1H, d, J = 3.7 Hz), 7.76 (1H, t, J = 1.1 Hz), 7.47 (1H,
(C–F), 1147 (C–O–C), 758, 700; 1H NMR (400 MHz, CDCl3):
d 7.40–
dd, J = 7.6, 1.3 Hz), 7.34 (1H, t, J = 7.8 Hz), 7.47 (1H, dd, J = 5.6,
2.2 Hz), 7.34 (1H, t, J = 7.8 Hz), 7.27 (1H, tt, J = 5.6, 2.2 Hz), 6.66 (1H,
dd, J = 3.7, 1.7 Hz), 3.58 (1H, t, J = 7.7 Hz, 3a-H), 2.47 (1H, d,
J = 13.5 Hz, 4-H), 2.32 (1H, m, 4-H), 1.88 (1H, m), 1.80 (2H, m), 1.63
7.29 (5H, m), 6.23 (1H, d, J = 0.6 Hz, Holef), 3.16 (1H, dd, J = 18.6,
0.7 Hz, 3-Ha), 2.84 (1H, ddd, J = 18.6, 6.4, 1.7 Hz, 3-Hb), 2.68 (1H, m,
3a-H), 2.22 (1H, tt, J = 15.3, 5.2 Hz), 1.92 (2H, m), 1.76 (1H, m), 1.67
(1H, m), 1.51 (1H, m), 1.45 (1H, m, 5-H), 1.25 (1H, m); 13C NMR
2
(1H, m), 1.41 (2H, t, J = 9.2 Hz); 13C NMR (100 MHz, CDCl3):
d
174.2
(100 MHz, CDCl3):
d
186.1 (C-2), 181.1 (q, JC-F = 33.8 Hz, C55O),
2
1
(q, JC-F = 34.3 Hz, C55O), 162.5 (C-2), 147.7, 145.8, 128.9, 128.3,
126.4, 124.9, 123.1, 119.4 (q, JC-F = 291.3 Hz, –CF3), 113.8, 113.4
(C-3), 93.5 (C-7a), 45.2 (d, 4JC-F = 1.8 Hz, C-3a), 36.4 (C-7), 31.2 (C-
144.8, 129.7, 129.1, 125.6, 117.8 (q, JC-F = 291.4 Hz, –CF3), 94.11
(C-7), 94.0 (C-3), 40.8 (C-6), 40.7 (C-5), 37.0, 28.9, 23.4, 21.9; 19F
1
NMR (376 MHz, CDCl3):
d
À78.7 (s, CF3); GC–MS (EI, 70 eV), m/z
4), 22.0 (C-6), 21.5 (C-5); 19F NMR (376 MHz, CDCl3):
d
À74.3 (s,
(%): 311 (MH+, 10.51), 310 (M+, 24.99), 241 (M+–CF3, 11.83), 170
(M+–CF3CO–C3H7, 14.23), 156 (M+–CF3CO–C3H5O, 100.00), 91
(PhCH2+, 69.37), 77 (C6H5+, 29.21), 69 (CF3+, 47.12). Anal. Calcd
for C17H17F3O2: C, 65.80; H, 5.52. Found: C, 65.75; H, 5.41.
3-(2-Furoyl)-2-(trifluoromethyl)-7a-phenyl-octahydro-1-ben-
zofuran-2-yl acetate (5a). Yield 36% (380 mg) as a colourless solid,
CF3); GC–MS (EI, 70 eV), m/z (%): 363 (MH+, 12.05), 362 (M+, 28.49),
344 (M+–H2O, 14.53), 293 (M+–CF3, 23.06), 265 (M+–CF3CO, 24.62),
262 (M+–C5H3O2, 34.60), 105 (PhCO+, 21.74), 95 (C5H3O2+, 100.00),
77 (C6H5+, 29.00), 69 (CF3+, 38.03), 55 (C4H7+, 14.98). Anal. Calcd for
C20H17F3O3: C, 66.29; H, 4.73. Found: C, 66.36; H, 4.92.
1-(2,7a-Diphenyl-3a,4,5,6,7,7a-hexahydro-1-benzofuran-3-
m.p. 156–158 8C (Hexane/EtOAc).
(C55O), 1679 (C55O), 1190 (C–F), 1088 (C–O–C), 764, 701; 1H NMR
(400 MHz, CDCl3): 7.61 (1H, d, J = 6.4 Hz), 7.56 (2H, d, J = 7.2 Hz),
7.36 (2H, t, J = 7.3 Hz), 7.30 (2H, m), 6.61 (1H, t, J = 5.8 Hz), 5.51 (1H,
d, J = 13.2 Hz, 3-H), 3.63 (1H, dd, J = 13.2, 6.0 Hz, 3a-H), 2.66 (1H, td,
J = 13.6, 3.2 Hz), 2.25 (3H, s, CH3), 2.18 (1H, dt, J = 13.4, 3.8 Hz), 1.88
(1H, m), 1.70 (2H, m), 1.58 (1H, m), 1.22 (1H, m); 13C NMR
ymax (KBr disc) 2938, 2864, 1762
yl)-2,2,2-trifluoroethanone (3k). Yield 32% (298 mg) as pale yellow
oil. ymax (KBr disc) 3055, 2930, 2861, 1681 (C55O), 1589 (C55C),
d
1199 (C–F), 1143 (C–O–C), 758, 694; 1H NMR (400 MHz, CDCl3):
d
7.76 (2H, td, J = 7.2, 1.4 Hz), 7.47–7.22 (8H, m), 3.57 (1H, t,
J = 7.2 Hz, 3a-H), 2.29 (2H, m), 1.78 (1H, m), 1.66 (2H, m), 1.52 (2H,
m), 1.45 (1H, m); 13C NMR (100 MHz, CDCl3):
d
175.9 (q, JC-
2
F = 34.5 Hz, C55O), 173.0 (C-2), 145.0, 132.1, 129.8, 128.4, 128.0,
127.7, 126.5, 124.2, 118.2 (q, JC-F = 289.5 Hz, –CF3), 111.3 (C-3),
92.3 (C-7a), 45.7 (C-3a), 35.6 (C-7), 29.7 (C-4), 20.8 (C-6), 20.7 (C-
(100 MHz, CDCl3): d 182.5 (C55O), 168.7 (C55O), 153.8, 146.9, 144.6,
128.3, 127.6, 125.7, 122.8 (q, JC-F = 287.2 Hz, –CF3), 117.9, 113.2,
105.6 (q, 2JC-F = 34.2 Hz, C-2), 88.2 (C-7a), 52.5, 42.9 (C-7), 36.6 (C-
1
1

634
M. Yılmaz, A.T. Pekel / Journal of Fluorine Chemistry 132 (2011) 628–635
4), 25.4, 22.7 (C-6), 20.4 (C-5); 19F NMR (376 MHz, CDCl3):
d
À78.0
References
(s, CF3); GC–MS (APCI, 100 eV), m/z (%): 422 (M+, 21.05), 421 (M+–
H, 13.62), 379 (M+–CH3CO, 34.13), 362 (M+–CH3CO2H, 100.00), 355
[1] (a) K. Uneyama, Organofluorine Chemistry, Blackwell, Oxford, 2006;
(b) P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, Germany,
2004;
(M+–C4H3O, 9.20), 309 (M+–CF3–CO2, 62.82), 266 (M+–C4H3F3O3,
23.30), 157 (C4H3F3O3+, 95.15), 95 (C5H3O2+, 4.30), 91 (PhCH2
,
(c) J. Greiner, J.G. Riess, P. Vierling, in: R. Filler, Y. Kobayashi, L.M. Yagupolski (Eds.),
Organofluorine Compounds in Medical Chemistry and Biomedical Applications,
Elsevier, Amsterdam, 1993, pp. 339–380;
(d) T. Hiyama, Organofluorine Compounds. Chemistry and Application, Springer-
Verlag, Berlin, 2000;
(e) R.D. Chambers, Fluorine in Organic Chemistry, Blackwell, Oxford, 2004;
(f) C. Isanbor, D. O’Hagan, J. Fluorine Chem. 127 (2006) 303–319;
(g) F.M.D. Ismail, J. Fluorine Chem. 118 (2002) 27–33.
+
29.85), 69 (CF3+, 9.13). Anal. Calcd for C22H21F3O5: C, 62.56; H 5.01.
Found: C, 62.72; H, 4.93.
3-Benzoyl-2-(trifluoromethyl)-7a-phenyl-octahydro-1-ben-
zofuran-2-yl acetate (5b). Yield 35% (378 mg) as a colourless
solid, m.p. 130–132 8C (Hexane/EtOAc). ymax (KBr disc) 2934,
2864, 1762 (C55O), 1685 (C55O), 1596 (C55C), 1203 (C–F), 1186 (C–
[2] (a) M.J. Tozer, T.F. Herpin, Tetrahedron 52 (1996) 8619–8683;
(b) J.M. Altenburger, D. Schirlin, Tetrahedron Lett. 32 (1991) 7255–7258;
(c) K. Brady, A.Z. Wei, D. Ringe, R.H. Abeles, Biochemistry 29 (1990) 7600–7607;
(d) T. Tanaka, M. Kawase, S. Tani, Life Sci. 73 (2003) 2985–2990;
(e) G. Spengler, A. Molnar, G. Klausz, Y. Mandi, M. Kawase, N. Motohashi, J.
Molnar, Int. J. Antimicrob. Agents 23 (2004) 631–633;
(f) R.R. Frey, C.K. Wada, R.B. Garland, M.L. Curtin, M.R. Michaelides, Bioorg. Med.
Chem. Lett. 12 (2002) 3443–3447.
[3] (a) M. Kawase, H. Harada, S. Saito, J. Cui, S. Tani, Bioorg. Med. Chem. Lett. 9 (1999)
193–194;
O–C), 762, 696; 1H NMR (400 MHz, CDCl3):
d 7.94 (2H, dd, J = 8.4,
1.2 Hz), 7.62 (1H, tt, J = 7.6, 1.2 Hz), 7.60 (2H, dt, J = 6.8, 1.6 Hz),
7.52 (2H, t, J = 7.6 Hz), 7.37 (2H, td, J = 8.0, 0.8 Hz), 7.29 (1H, tt,
J = 7.2, 1.2 Hz), 5.63 (1H, d, J = 12.8 Hz, 3-H), 3.65 (1H, dd, J = 12.8,
5.8 Hz, 3a-H), 2.65 (1H, td, J = 13.2, 3.6 Hz, 4-H), 2.15 (3H, s, –CH3),
2.20 (1H, m), 1.76 (2H, m), 1.92 (1H, m), 1.65 (2H, m), 1.52 (1H,
m); 13C NMR (100 MHz, CDCl3):
d 194.7 (C55O), 168.8 (C55O),
1
(b) M. Kawase, N. Motohashi, H. Sakagami, T. Kanamoto, H. Nakashima, L.
Ferenczy, K. Wolfard, C. Miskolci, J. Molna´r, Int. J. Antimicrob. Agents 18
(2001) 161–165;
(c) A. Molna´r, K. Wolfart, M. Kawase, N. Motohashi, J. Molna´r, In Vivo 18 (2004)
505–507.
144.5, 138.3, 133.9, 128.4, 128.2, 127.7, 125.8, 122.0 (q, JC-
F = 287.2 Hz, –CF3), 116.0 (q, 2JC-F = 34.2 Hz, C-2), 88.3 (C-7a), 52.3
(CH3), 44.5, 43.2, 36.6, 25.4, 22.2, 20.6; 19F NMR (376 MHz,
CDCl3):
d
À73.6 (s, CF3); GC–MS (APCI, 100 eV), m/z (%): 432 (M+,
[4] M. Kawase, H. Sakagami, K. Kusama, N. Motohashi, S. Saito, Bioorg. Med. Chem.
Lett. 9 (1999) 3113–3118.
[5] (a) T. Kitazume, T. Yamazaki, Experimental Methods in Organic Fluorine Chem-
istry, Gordon and Breach Science, Amsterdam, 1998.
1.71), 431 (M+–H, 13.20), 389 (M+–CH3CO, 11.12), 373 (M+–
CH3CO2, 26.00), 371 (M+–CH3CO2H, 100.00), 355 (M+–C6H5,
29.81), 335 (M+–CF3CO, 17.23), 277 (MH+–C4H3F3O3, 28.41),
157 (C4H4F3O3+, 73.30), 105 (PhCO+, 55.20), 91 (PhCH2+, 24.90),
77 (C6H5+, 11.42). Anal. Calcd for C24H23F3O4: C, 66.66; H, 5.36.
Found: C, 66.82; H, 5.14.
(b) M. Hudlicky´, A.E. Pavlath, Chemistry of Organic Fluorine Compounds II,
American Chemical Society, Washington, DC, 1995;
(c) G.Q. Shi, Y.Y. Xu, M. Xu, Tetrahedron 47 (1991) 1629–1648.
[6] (a) S. Leconte, R. Ruzziconi, J. Fluorine Chem. 117 (2002) 167–172;
(b) Y. Wang, S. Zhu, Tetrahedron 57 (2001) 3383–3387.
[7] (a) A. Citterio, R. Santi, T. Fiorani, S. Strologo, J. Org. Chem. 54 (1989) 2703–2712;
(b) A. Citterio, D. Fancelli, C. Finzi, L. Pesce, J. Org. Chem. 54 (1989) 2713–2718;
(c) J.M. Mellor, S. Mohammed, Tetrahedron Lett. 32 (1991) 7111–7114;
(d) J.M. Mellor, S. Mohammed, Tetrahedron 49 (1993) 7547–7556;
(e) H. Nishino, V.-H. Hguyen, S. Yoshinaga, K. Kurosawa, J. Org. Chem. 61 (1996)
8264–8271;
2-(Heptafluoropropyl)-7a-phenyl-3-(2-thienylcarbonyl)octahy-
dro-1-benzofuran-2-yl acetate (5c). Yield 41% (441 mg) as yellow
oil.
y
max (KBr disc) 2975, 2926, 1714 (C55O), 1650 (C55O), 1240 (C–F),
934 (C–O–C), 749, 693.; 1H NMR (400 MHz, CDCl3):
d
7.70 (1H, m),
7.50 (2H, dd, J = 7.2, 1.6 Hz), 7.35(2H, t, J = 6.4 Hz), 7.28(t, J = 6.8 Hz),
7.17 (dd, J = 4.8, 4.0 Hz), 5.68 (1H, d, J = 13.2 Hz, 3-H), 3.79 (1H, dd,
J = 13.2, 6.4 Hz, 3a-H), 2.78 (1H, td, J = 14.0, 4.0 Hz, 7-H), 2.19 (3H, s,
CH3), 2.07 (1H, m), 1.95 (1H, m), 1.80 (1H, m), 1.64 (2H, m), 1.49 (1H,
(f) F. Garzino, A. Me´ou, P. Brun, Tetrahedron Lett. 41 (2000) 9803–9807;
(g) B. Gregory, A.F. Parsons, C.B. Thomas, Tetrahedron Lett. 41 (2000) 7751–7755;
(h) S. Kajikawa, H. Nishino, K. Kurosawa, Heterocycles 54 (2001) 171–183;
(i) B. Gregory, A.F. Parsons, C.B. Thomas, Tetrahedron 57 (2001) 4719–4728;
(j) G.G. Melikyan, Synthesis (1993) 833–850;
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7088–7095;
m), 1.14 (1H, m); 13C NMR (100 MHz, CDCl3):
d 186.3 (C55O), 169.2
(C55O), 145.9, 144.8, 135.1, 132.0, 128.5, 128.0, 127.5, 125.8,
2
coupling constants of CF2CF2CF3 are not determined, 108.2 (t, JC-
3
F = 34,6 Hz, C-2), 89.4, 54.2, 42.7 (d, JC-F = 5.3 Hz, C-3), 37.2, 25.8,
22.9, 22.5, 20.7; 19F NMR (376 MHz, CDCl3):
d
À80.6 (t, J = 9.4 Hz,
(n) X.-Q. Pan, J.-P. Zou, W. Zhang, Mol. Divers. 13 (2009) 421–438;
(o) R. Caliskan, T. Pekel, W. Watson, M. Balci, Tetrahedron Lett. 46 (2005)
6227–6230;
CF2CF2CF3), À118,0 (q, J = 9.3 Hz, CF2CF2CF3), À126.7 (t, J = not
determined CF2CF2CF3); LC–MS (ESI+), m/z (%): 538 (MH+ – HOAc,
100%). Anal. Calcd for C24H21F7O4S: C, 53.53; H, 3.93; S, 5.95. Found:
C, 53.47; H, 4.04; S, 5.87.
(p) A.S. Demir, M. Emrullahoglu, Curr. Org. Synth. 4 (2007) 223–237;
(q) E.I. Heiba, R.M. Dessau, J. Am. Chem. Soc. 96 (1974) 3456–3457;
(r) E.I. Heiba, R.M. Dessau, J. Am. Chem. Soc. 94 (1972) 2888–2889.
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2-(Trifluoromethyl)-3-(2-naphthoyl)-7a-phenyl-octahydro-1-
benzofuran-2-yl acetate (5d). Yield 30% (290 mg) as yellow oil.
ymax (KBr disc) 3026, 2959, 1718 (C55O), 1633 (C55O), 1026, 761,
(c) K. Kobayashi, K. Sakashita, H. Akamatsu, K. Tanaka, M. Uchida, T. Uneda, T.
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939–946;
(i) Y.-L. Wu, C.-P. Chuang, Tetrahedron 60 (2004) 1841–1847;
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(k) V. Nair, K. Mohanan, T.D. Suja, E. Suresh, Tetrahedron Lett. 47 (2006)
2803–2806;
697; 1H NMR (400 MHz, CDCl3):
d 8.46 (1H, s), 8.03 (1H, d,
J = 8.8 Hz), 7.98–7.89 (3H, m), 7.63–7.57 (4H, m), 7.37 (2H, t,
J = 7.2 Hz), 7.29 (1H, tt, J = 7.2, 1.2 Hz), 5.82 (1H, d, J = 12.8 Hz, 3-H),
3.77 (1H, dd, J = 12.8, 5.6 Hz, 3a-H), 2.72 (1H, td, J = 13.6, 4.0 Hz),
2.23 (1H, m), 2.13 (3H, s, CH3), 1.79 (2H, m), 1.69–1.56 (2H, m), 1.25
(2H, m); 13C NMR (100 MHz, CDCl3):
d 194.2 (C55O), 168.6 (C55O),
144.2, 136.0, 135.8, 132.3, 130.1, 128.7, 128.6, 128.5, 128.0, 127.9,
127.7, 126.3, 126.1, 124.1, 122.3 (q, 1JC-F = 286.3 Hz, –CF3), 106 (q,
2JC-F = 34.4 Hz, C-2), 88.2, 52.1, 42.5, 36.3, 24.7, 22.2, 20.3; 19F NMR
(l) K. Bahrami, M.M. Khodaei, F. Naali, J. Org. Chem. 73 (2008) 6835–6837.
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(376 MHz, CDCl3):
– HOAc, 100%). Anal. Calcd for C28H25F3O4: C, 69.70; H, 5.52. Found:
C, 69.85; H, 5.67.
d
À76.4 (s, 3F); LC–MS (ESI+), m/z (%): 482 (MH+
(b) F.M. Dean, M.V. Sargent, in: C.W. Bird, G.W.H. Cheeseman (Eds.), Compre-
hensive Heterocyclic Chemistry, vol. 4, Pergamon, New York, 1984, pp. 531–
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Acknowledgments
The authors are grateful to the Ankara University (BAP
20030705076) and the Kocaeli University (BAP 2008/28) Science
Research Foundations for their financial supports.

M. Yılmaz, A.T. Pekel / Journal of Fluorine Chemistry 132 (2011) 628–635
635
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