A novel synthesis of fluorine-containing cyclopentenones via Pauson-Khand reaction

Article abstract of DOI:10.1016/j.jfluchem.2012.08.006

Intermolecular Pauson-Khand reaction of fluoroalkylated alkynes with 2-norbornene or 2,5-norbornadiene at the reflux temperature of dichloroethane proceeded smoothly to give the corresponding cyclopentenone derivatives in high yields as a mixture of regio

Full text of DOI:10.1016/j.jfluchem.2012.08.006

Journal of Fluorine Chemistry 144 (2012) 147–156
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
A novel synthesis of fluorine-containing cyclopentenones via Pauson–Khand
reaction
*
Tsutomu Konno , Takumi Kida, Akinori Tani, Takashi Ishihara
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
Intermolecular Pauson–Khand reaction of fluoroalkylated alkynes with 2-norbornene or 2,5-norborna-
diene at the reflux temperature of dichloroethane proceeded smoothly to give the corresponding
cyclopentenone derivatives in high yields as a mixture of regioisomers. On the other hand, intramolecular
Pauson–Khand reaction of fluorine-containing 1,6-enyne proceeded in the presence of NMO or TMANO
to give the bicyclic adducts in good yields. Additionally, allyl CF3-propargyl ether also underwent a
smooth Pauson–Khand reaction in the presence of amine oxide, the corresponding bicyclic compounds
being obtained in a highly diastereoselective manner.
Received 5 July 2012
Received in revised form 24 August 2012
Accepted 26 August 2012
Available online 1 September 2012
Keywords:
Fluorine-containing cyclopentenone
ß 2012 Elsevier B.V. All rights reserved.
Pauson–Khand
NMO
TMANO
1. Introduction
at room temperature for 2 h gave the corresponding alkyne–cobalt
complex 3a in quantitative yield. Without isolation, 3.0 equiv. of 2-
2-Cyclopentenone derivatives occupy a central position in
organic synthesis owing to their wide utility as potent synthetic
blocks, particularly as Michael acceptors for conjugate addition
reactions, dienophiles and dipolarophiles for cycloaddition reac-
tions, and so on [1]. 2-Fluoroalkyl-2-cyclopentenones 1, shown in
Fig. 1, are likewise of great synthetic value as building blocks for
constructing various types of fluorine-containing compounds,
which attract much attention in biological and materials chemis-
try. Therefore, it is a very significant subject to develop a
convenient and effective route to such fluorinated cyclopente-
nones and related compounds. Nevertheless, there have been quite
limited studies on the preparation of 2-fluoroalkyl-2-cyclopente-
none derivatives thus far [2]. Herein is disclosed a convenient
synthetic approach to 1 via Pauson–Khand reaction [3] by using
fluoroalkylated alkynes in detail [4].
norbornene was added into the reaction mixture, and then the
whole was stirred at room temperature for 6 h. However, no
desired product was obtained and the alkyne–cobalt complex was
recovered almost quantitatively (Entry 1). On the other hand, the
reaction at the reflux temperature gave the corresponding adducts
in excellent yield (Entry 2). In this case the product was obtained as
a diastereomeric mixture in a ratio of 68:32 of 4a and 5a [6].
Addition of 1,4-dioxane or MeSPh did not lead to a significant
influence on the reaction at all (Entries 3 and 4). In sharp contrast,
amine oxide, which is recognized as a very effective promoter for
Pauson–Khand reaction in the non-fluorinated system [7], led to a
significant decrease of the yield (Entry 5). Several attempts to
improve the yield in the amine oxide-promoted Pauson–Khand
reaction were fruitless as shown in Entries 6 and 7.
We next examined the Pauson–Khand reaction of various
trifluoromethylated internal alkynes under the reflux conditions
without a promoter. The results are summarized in Table 2.
As shown in Entries 1–3, the alkynes having an electron-
withdrawing or an electron-donating group on the benzene ring
were found to be good substrates, the corresponding cyclopente-
nones 4 and 5 being obtained in high yields as a diastereomeric
mixture in a ratio of ca. 70:30. The position of the substituent on
the benzene ring slightly influenced on the yield (Entries 3–5).
Additionally, the opposite regioselectivity was observed in the case
of the alkyne 2e having an ortho-substituted aryl group as R (Entry
5). Use of an alkyl substituent and an ethoxycarbonyl group as R
caused a significant improvement of the regioselectivity, 4f and 4g
2. Results and discussion
2.1. Intermolecular Pauson–Khand reaction
Our initial studies focused on the intermolecular Pauson–Khand
reaction of trifluoromethylated internal alkyne 2a (Rf = CF3, R = p-
ClC6H4) [5] and 2-norbornene as shown in Scheme 1 and Table 1.
Thus, treatment of 2a with 1.2 equiv. of Co2(CO)8 in dichloroethane
* Corresponding author.
E-mail address: konno@chem.kit.ac.jp (T. Konno).
being obtained preferentially (Entries 6 and 7). When the
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.08.006

148
T. Konno et al. / Journal of Fluorine Chemistry 144 (2012) 147–156
Table 2
O
Intermolecular Pauson–Khand reaction of various alkynes with 2-norbornene.
Rf
Entry
Rf
R
Yielda/%
Isomer ratiob
of 4 + 5
(4:5)
1
1
2
3
4
5
6
7
8
9
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CHF2
p-ClC6H4 (a)
92
91
90
86
(72)c
57
69
0
68:32
73:27
71:29
69:31
22:78
93:7
p-EtO2CC6H4 (b)
p-MeOC6H4 (c)
m-MeOC6H4 (d)
o-MeOC6H4 (e)
p-MeOC6H4CH2 (f)
EtO2C (g)
Fig. 1. 2-Fluoroalkyl-2-cyclopentenones.
Table 1
100:0
–
Investigation of the reaction conditions (a: Rf = CF3, R = p-ClC6H4).
Yielda/% Isomer ratioa Recoverya/% Recoverya/%
of 4a + 5a (4a:5a)
PhMe2Si (h)
p-MeOC6H4 (i)
77
31:69
Entry Promoter
a
Isolated yield. Value in parentheses is the yield determined by 19F NMR.
Determined by 19F NMR.
of 3a
of 2a
b
c
1b
2
None
None
0
–
68:32
73:27
78:22
69:31
71:29
88:12
92
4
0
0
The product could not be completely purified because of impurities.
(92)
3
1,4-Dioxane 99
Trace
0
0
4
MeSPh
NMO
NMO
NMO
94
50
59
12
0
5
0
0
6c
7b
12
32
0
reported that the 13C NMR signal of
group in the known compound 6 appears at the upper field than
that of -carbon having ca. 3 Hz as a coupling constant, though
2J(C, F) has not been described in the literature [2d]. Consequently,
the structure of 4 was determined to be the exo-adduct having a
CF3 group at 2 position, while 5 was determined to be the exo-
adduct having a CF3 group at 3 position [6].
a-carbon attached with a CF3
13
Determined by 19F NMR. Value in parentheses is of isolated yield.
Carried out at room temperature.
a
b
b
c
Refluxed for 2 h.
difluoromethylated alkyne 2i was used, the reaction took place
very smoothly to afford the corresponding 5i preferentially, like
the reaction of 2e (vide infra) (Entry 9).
2.3. Reaction mechanism
We also investigated the Pauson–Khand reaction using various
non-fluorinated alkenes. Although the reaction with 2,5-norbor-
nadiene afforded the corresponding cyclopentenone 4j and 5j in
good yield (Scheme 2), the other alkenes, such as cyclohexene,
maleic anhydride, ethylene carbonate, and 1-octene, did not give
any trace of the desired products at all.
It has been well recognized that the regiochemistry could be
significantly influenced by steric as well as electronic effect in
Pauson–Khand reaction of internal alkynes, which leads to a
difficult prediction of the regioselectivity. Generally, the bulkier
group on the alkynes tends to be located at
a position to the
carbonyl group. When the substituents on the alkynes are
sterically similar, the more strongly electron-withdrawing group
2.2. Regioselectivity
tends to be located at the
(Scheme 3) [2d,8].
b position to the carbonyl group
The regiochemical assignment was carried out based on the 13
C
NMR chemical shifts of the signals having the coupling constants
2J(C, F) or 3J(C, F). In general, it has been recognized in CF3-
containing materials that the coupling constant 2J(C, F) is ca. 30–
40 Hz, while 3J(C, F) is ca. 3–5 Hz. The chemical shifts as well as the
coupling constants of the Pauson–Khand reaction products 4a–g,
5a and b are collected in Table 3. In the compound 4, the signal
having a larger coupling constant 2J(C, F) appears at the upper field
than the signal having a smaller coupling constant 3J(C, F). The
opposite situation can be observed in 5. Additionally, it has been
In the present study, the steric factor, not the electronic factor,
might play an important role in the regioselectivity. Thus, a CF3
group, which is considered to be similar to an isopropyl group in
size [9], might be bulkier than a phenyl as well as an alkyl
functionality, resulted in a preferential formation of 4. On the other
hand, an ortho-substituted aryl group is much bulkier than a meta-
and a para-substituted ones, and maybe a CF3 group, leading to a
preferential formation of 5. Additionally, a CHF2 group might be a
smaller substituent, compared to an aryl group as well as a CF3
(3.0 eq.)
Co2(CO)6
Co2(CO)8
(1.2 eq.)
Promoter
(2.0 eq.)
O
Rf
O
R
Rf
R
+
Rf
R
reflux, 6 h
ClCH2CH2Cl
r.t., 2 h
2
3
H
H
Rf
R
H
H
4
5
Scheme 1. Intermoleclar Pauson–Khand reaction.
Co2(CO)
Co2(CO)
(1.2 eq.8)
6
O
CF3
O
R
(3.0 eq.)
F3C
R
+
F3C
R
reflux, 6 h
ClCH CH2Cl
r.t.2, 2 h
2
3
H
H
R
CF3
H
H
5j
4j
R = p-ClCH4
6
68% isolated yield
(4j : 5j = 84 : 16)
Scheme 2. Intermolecular Pauson–Khand reaction with 2,5-norbornadiene.

T. Konno et al. / Journal of Fluorine Chemistry 144 (2012) 147–156
149
Table 3
The chemical shifts of the signals having 2J(C, F) or 3J(C, F) in 13C NMR of 4 and 5.
4
5
a
-Carbon: 2J(C, F)
b
-Carbon: 3J(C, F)
a
-Carbon: 2J(C, F)
b
-Carbon: 3J(C, F)
a
b
c
d
f
133 (q, J = 31 Hz)
134 (q, J = 31 Hz)
131 (q, J = 31 Hz)
133 (q, J = 31 Hz)
133 (q, J = 31 Hz)
134 (q, J = 33 Hz)
177 (q, J = 3 Hz)
178 (q, J = 3 Hz)
178 (q, J = 3 Hz)
179 (q, J = 3 Hz)
182 (q, J = 2 Hz)
167 (q, J = 3 Hz)
148 (q, J = 3 Hz)
148 (q, J = 3 Hz)
155 (q, J = 32 Hz)
156 (q, J = 32 Hz)
g
O
α-Carbon : 2J(C, F)
CF3
138 ppm (The splitting pattern was not shown in
the literature.)
H
CO2Et
H
6
β-Carbon : 3J(C, F)
167 ppm (q, JCF = 3 Hz)
O
O
R2
1
R1
R1
R2
+
Co2(CO)
8
2
H
H
R
R
H
H
Major isomer
Minor isomer
R1 > R2 in size
and/or
R1 = EDG (an electron-donating group)
R2 = EWG (an electron-withdrawing group)
Scheme 3. Regioselectivity.
OAc
Ac2O (2.0 equiv.)
Pyridine (2.0 equiv.)
F3C
F3C
CH2Cl2, r.t., 12 h
(1.5 equiv.)
1)
2)
Br
OH
LDA (3.0 equiv.)
THF, -78 °C, 20 min
H+
7b : 89%
F3C
H
O
OTBS
TBSCl (2.0 equiv.)
Imidazole (5.0 equiv.)
7a
F3C
DMF, 70 °C, 10 h
7c : 69%
Scheme 4. Preparation of various trifluoromethylated enynes.
group [10], therefore the
derivative 5 being obtained preferentially.
b
-difluoromethylated cyclopentenone
1.5 equiv. of NaH and 4.0 equiv. of DMPU in THF at room
temperature for 20 min, the corresponding propargyl ethers being
obtained in good to high yields (Scheme 5).
2.4. Intramolecular Pauson–Khand reaction
With these substrates, we next examined the intramolecular
Pauson–Khand reaction in detail (Table 4). Thus, treatment of 7a
with 1.2 equiv. of Co2(CO)8 in dichloroethane at room temperature
for 1 h gave the corresponding alkyne–cobalt complex, 10a.
Without isolation, the complex was allowed to heat at the reflux
temperature for 6 h. In sharp contrast to the intermolecular
Pauson–Khand reaction, the desired [2+2+1] cyclization product
was obtained in only 14% yield, and neither the starting material
nor the alkyne–cobalt complex were observed (Entry 1). When the
reaction mixture was stirred for only 1 h, the desired bicyclic
compounds 11a was obtained in 43% yield as a diastereomeric
mixture in a ratio of ca. 1:1. In this case, however, any trace of
starting alcohol as well as alkyne–cobalt complex was not detected
at all (Entry 2). The reaction at room temperature led to 80%
recovery of the alkyne–cobalt complex (Entry 3).
Our attention was next directed toward the intramolecular
Pauson–Khand reaction using fluorine-containing 1,6-enynes or
ally propargyl ethers.
Various substrates could be prepared according to the
conventional method as shown in Schemes 4 and 5. Thus, the
nucleophilic addition of trifluoromethylated acetylide with 2,2-
dimethyl-4-pentenal afforded 1,1,1-trifluoro-5,5-dimethyl-7-
octen-2-yn-4-ol (7a) in a good yield [11]. The alcohol could be
easily converted into the corresponding acetate 7b and the silyl
ether 7c.
On the other hand, the alcohols 8a–f, prepared readily from 2-
bromo-3,3,3-trifloropropene and the corresponding aldehydes,
were subjected to 4.0 equiv. of allyl bromide in the presence of

150
T. Konno et al. / Journal of Fluorine Chemistry 144 (2012) 147–156
1
R2 =H
Br
n-C H
(4.0equiv.)
(a)
(b)
(c)
(d)
(e)
(f)
Rf =
R =
CF3
CF3
CF3
CF3
CF3
6
PhCH1C3 H2
R1
R2
O
NaH(1.5 equiv.)
DMPU(4.0 equiv.)
H
H
H
-
R1
R2
OH
2
Rf
Cy
Rf
Et2CH
-(CH2)5-
n-C6H13
THF,r.t., 20 min
8a-f
CHF2
H
9a-f
51 - 98%
Scheme 5. Preparation of various fluorinated propargyl ethers.
Table 4
Intramolecular Pauson–Khand reaction of various enynes
Co2(CO)6
OR
F3C
OR
OR
F3C
Co2(CO)8 (1.2 eq.)
THF, r.t., 1 h
Additive
r.t., 1 h
F3C
O
H
11a-c
7a
: R = H
7b : R = Ac
7c
10a-c
: R = TBDMS
..
Entry
R
Additive (equiv.)
Yielda,b
/
Isomer ratioa
Recoverya/
Recoverya
% of 11
% of 10
% of 7
1c,d
2c,e
3f
H (a)
None
14
33:67
44:56
–
0
0
0
0
H (a)
None
43
H (a)
None
0
80
76
3
0
4
H (a)
None
5
57:43
44:56
58:42
54:46
61:39
44:56
36:64
46:54
38:62
23:77
0:100
37:63
41:59
0
5
H (a)
NMO (1.5)
NMO (3.0)
TMANO (1.5)
TMANO (3.0)
NMO (1.5)
NMO (3.0)
TMANO (1.5)
TMANO (3.0)
NMO (3.0)
NMO (6.0)
TMANO (3.0)
TMANO (6.0)
58
0
6
H (a)
60
0
0
7
H (a)
39
27
0
0
8
H (a)
69 (67)
41
0
9
Ac (b)
11
0
0
10
11
12
13
14
15
16
Ac (b)
37
0
Ac (b)
54 (52)
44
10
3
0
Ac (b)
0
TBDMS (c)
TBDMS (c)
TBDMS (c)
TBDMS (c)
35
0
48
44
38
44
9
0
47
0
56 (53)
0
a
Determined by 19F NMR.
b
c
d
e
f
Values in parentheses are of isolated yield.
Carried out with 1.2 equiv. of Co2(CO)8 in ClCH2CH2Cl.
The reaction mixture of 10a was refluxed for 6 h.
The reaction mixture of 10a was refluxed for 1 h.
Carried out in ClCH2CH2Cl.
Then, we next investigated the promoter as shown in Entries
the products were obtained as an almost 1: 1 diastereomeric
mixture.
4–8. Thus, on treating 7a with Co2(CO)8 in THF at room
temperature for 1 h, the corresponding alkyne–cobalt complex
10a was afforded, similar to the reaction in dichloroethane.
Without isolation, the complex was exposed to 1.5 equiv. of
N-methylmorpholine-N-oxde (NMO) at room temperature for 1 h,
giving the corresponding bicyclic compounds, 11a in 58% yield in a
stereorandam manner (Entry 5), while only a trace amount of the
Pauson–Khand product was detected in the absence of NMO (Entry
4). Increase of the amount of NMO did not lead to a dramatic
improvement of the yield (Entry 6), however, the reaction in the
presence of 3.0 equiv. of trimethylamine-N-oxide (TMANO) gave
the better result rather than the reaction in the presence of
1.5 equiv. of TMANO (Entries 7 and 8).
As shown in Entries 9–16, we also examined the intramolecular
Pauson–Khand reaction using 7b and 7c. After several attempts,
the acetate 7b afforded the desired CF3-cyclopentenone derivative
11b in 54% yield when the reaction was performed in the presence
of 1.5 equiv. of TMANO, while the reaction with 7c required much
more amount of TMANO to produce 11c in 56% yield. In all cases,
Very interestingly, the Pauson–Khand reaction of fluorinated
propargyl ally ether 9a in the presence of TMANO took place
relatively smoothly to give the corresponding bicyclic adduct 12a
in a highly diastereoselective manner (Table 5, Entry 1). In this
case, only the corresponding cis adduct was detected, and no trans
isomer could not be obtained at all. The similar diastereoselectivity
could be observed in the other fluorinated allyl propargyl ether 9b–
d, the corresponding bicyclic products being afforded in a highly
cis-selective manner. However, 9e was found to be less reactive in
Pauson–Khand reaction (Entry 5). In addition, changing
a
fluoroalkyl group from a CF3 group to a CHF2 group caused a
significant influence on the reaction, and no product was given at
all (Entry 6).
2.5. Stereochemistry
The stereochemical assignment of 12 was determined based on
the NOE experiment of 12a. Thus, a NOE between Ha at
d 3.3 and

T. Konno et al. / Journal of Fluorine Chemistry 144 (2012) 147–156
151
Table 5
Intramolecular Pauson–Khand reaction of allyl propargyl ethers
Co2(CO)6
R1
R1
R1
R2
O
Rf
R2
R2
Co2(CO)8 (1.0 eq.)
THF, r.t., 1 h
Rf
Additive
r.t., 1 h
Rf
O
O
O
H
9a-f
12a-f
..
Entry
Rf
R1
R2
Additive (equiv.)
Yielda,b/% of 12
1
2
3
4
5
6
CF3
CF3
CF3
CF3
CF3
CHF2
n-Hex (a)
H
H
H
H
TMANO (3.0)
NMO (1.5)
NMO (1.5)
NMO (3.0)
NMO (1.5)
NMO (1.5)
(50)
46 (45)
46 (35)
57 (51)
28
PhCH2CH2 (b)
c-Hex (c)
Et2CH (d)
–(CH2)5– (e)
n-Hex (f)
H
0
a
Determined by 19F NMR.
b
Values in parentheses are of isolated yield.
Hb
spectrometer was used for determining the yields of the products
with internal hexafluorobenzene (C6F6), trifluoromethylbenzene
(BTF), or ethyl trifluoroacetate (TFA). It was also used for the
determining regioselectivity and stereoselectivity. High-resolution
mass spectra (HRMS) were measured with a JEOL JMS-700 mass
spectrometer by electron impact (EI), chemical ionization (CI), or
fast atom bombardoment (FAB) method.
Hb
n-C5 H 11
F3C
NOE
O
O
Ha
12a
4.1.1. Materials
Fig. 2. NOE experiment of 12a.
All chemicals were of reagent grade, and if necessary, were
purified in the usual manner prior to use. Thin layer chromatogra-
phy (TLC) was done with Merck 25 aluminium sheets (silica gel 60
Hb at
d 1.7 in 12a in the NOESY experiment was observed,
indicating that Ha and n-C6H13 group is in the cis configuration
F254). Column chromatography was carried out with Wakogel C-
relationship (Fig. 2).
200. All reactions were carried out under argon atmosphere.
3. Conclusion
4.2. General procedure for the intermolecular Pauson–Khand reaction
In summary, we have demonstrated the intermolecular as well
as intramolecular Pauson–Khand reaction by using a variety of
fluorinated alkynes. The reaction of the alkynes with 2-norbornene
and 2,5-norbornadiene in the presence of a stoichiometric amount
of Co2(CO)8 at the reflux temperature of dichloroethane took place
very smoothly to give the corresponding exo-adducts in high
yields.
On the other hand, fluorinated 1,6-enynes as well as allyl
propargyl ethers underwent a smooth Pauson–Khand reaction
under the influence of amine oxide, like NMO or TMANO, affording
the bicyclic compounds in good yields. It was noteworthy that
Pauson–Khand reaction by using propargyl allyl ethers gave the
adducts in a highly cis-selective manner, while 1,6-enynes afforded
the bicyclic compounds in a stereorandam manner.
To a solution of di-cobalt octacarbonyl, Co2(CO)8 (103 mg,
0.30 mmol) in 1,2-dichloroethane (2.0 mL) was added fluorine-
containing internal alkynes 2 (0.25 mmol) at r.t. After stirring for
2 h at r.t., the reaction mixture was cooled to 0 8C and 2-
norbornene (71 mg, 0.75 mmol) was added to the solution. The
whole was heated to the reflux temperature (ca. 84 8C) and stirred
for 6 h at that temperature. Then the reaction mixture was again
cooled to r.t., filtrated without quenching, and concentrated in
vacuo. The residue was chromatographed on silica gel to afford the
corresponding cyclopentenone derivatives 4 and 5.
4.2.1. 3-(4-Chlorophenyl)-2-trifluoromethyl-3a,4,5,6,7,7a-
hexahydro-4,7-methanoinden-1-one (4a)
Yield: 63%; 1H NMR (CDCl3)
d = 1.04 (d, J = 10.84 Hz, 1H), 1.12
(d, J = 10.84 Hz, 1H), 1.32–1.36 (m, 2H), 1.61–1.68 (m, 2H), 2.00 (br
s, 1H), 2.47 (d, J = 5.54 Hz, 1H), 2.58 (br s, 1H), 3.05 (br d, J = 3.14 Hz,
1H), 7.28–7.31 (m, 2H), 7.42–7.45 (m, 2H); 13C NMR (CDCl3)
4. Experimental
4.1. General experimental procedures
d
= 28.33, 28.91, 31.47, 38.14, 39.69, 53.01, 54.30, 121.21 (q,
J = 273.53 Hz), 128.66, 128.89, 132.19, 133.01 (q, J = 30.94 Hz),
136.72, 177.28 (q, J = 2.51 Hz), 203.15; 19F NMR (CDCl3)
Infrared spectra (IR) were recorded on a Shimadzu FTIR-8200A
(PC) spectrophotometer and Thermo Electron Corp AVATAR
370DTGS spectrophotometer. 1H NMR (500.13 MHz) and 13C
d
= À60.43
(s, 3F); IR (neat) 2962, 2916, 2878, 1717, 1639, 1593, 1491, 1456,
1400, 1366, 1308, 1269, 1236, 1188, 1167, 1130, 1094, 1067, 1014,
984, 937 cmÀ1; HRMS (FAB+) Calcd for (M+H) C17H15ClF3O:
327.0764, Found 327.0768.
NMR (125.75 MHz) spectra were measured with
a Bruker
DRX500 spectrometer or a JEOL JNM-AL400 spectrometer in a
chloroform-d (CDCl3) solution with tetramethylsilane (TMS) as an
internal reference. 19F NMR spectra were measured with a Bruker
DPX300 (282.38 MHz) spectrometer or
spectrometer (376.05 MHz) in a CDCl3 solution containing CFCl3
as an internal reference. A JEOL JNM-EX90A (84.21 MHz, FT)
4.2.2. 2-(4-Chlorophenyl)-3-trifluoromethyl-3a,4,5,6,7,7a-
hexahydro-4,7-methanoinden-1-one
a JEOL JNM-AL400
Yield: 29%; 1H NMR (CDCl3)
d
= 1.15 (br s, 2H), 1.35–1.46
(m, 2H), 1.62–1.68 (m, 1H), 1.76–1.82 (m, 1H), 2.47 (d,

152
T. Konno et al. / Journal of Fluorine Chemistry 144 (2012) 147–156
J = 3.35 Hz,1H), 2.56 (br s, 2H), 2.94 (d, J = 5.37 Hz, 1H),
7.18–
d = 28.34, 28.91, 31.47, 38.11, 39.68, 53.15, 54.26, 55.32, 112.99,
115.48, 119.45, 121.28 (q, J = 273.29 Hz), 129.63, 132.68 (q,
J = 31.19 Hz), 135.15, 159.39, 178.85 (q, J = 2.77 Hz), 203.46; 19F
7.21 (m, 2H), 7.37–7.40 (m, 2H); 13C NMR (CDCl3)
d
= 28.22, 29.02,
31.30, 38.20, 40.15, 47.29, 53.62, 122.59 (q, J = 274.30 Hz), 127.41,
128.46, 130.22, 135.40, 147.61 (q, J = 3.27 Hz), 155.47 (q,
NMR (CDCl3)
d
= À60.40 (s, 3F); IR (neat) 2963, 2916, 2878, 1717,
J = 32.20 Hz), 207.33; 19F NMR (CDCl3)
d
= À60.65 (s, 3F); IR (neat)
1641, 1599, 1578, 1489, 1454, 1431, 1366, 1290, 1267, 1202, 1169,
1128, 1096, 1078, 1045 cmÀ1; HRMS (FAB+) Calcd for (M+H)
C18H18F3O2: 323.1259, Found 323.1254.
2962, 2930, 2876, 2856, 2360, 2343, 1720, 1595, 1493, 1458, 1400,
1366, 1304, 1246, 1232, 1177, 1159, 1132, 1113, 1094, 1016 cmÀ1
;
HRMS (FAB+) Calcd for (M+H) C17H15ClF3O: 327.0764, Found
327.0770.
4.2.8. 3-Trifluoromethyl-2-(3-methoxyphenyl)-3a,4,5,6,7,7a-
hexahydro-4,7-methanoinden-1-one
4.2.3. 3-(4-Ethoxycarbonylphenyl)-2-trifluoromethyl-3a,4,5,6,7,7a-
Yield: 27%; 1H NMR (CDCl3)
d = 1.02–1.15 (m, 2H), 1.28–1.38
hexahydro-4,7-methanoinden-1-one (4b)
(m, 2H), 1.54–1.60 (m, 1H), 1.68–1.73 (m, 1H), 2.39 (d, J = 5.31 Hz,
1H), 2.49 (br s, 2H), 2.86 (d, J = 5.35 Hz, 1H), 3.73 (s, 3H), 6.70 (s,
1H), 6.75 (d, J = 8.01 Hz, 1H), 6.86 (d, J = 8.01, 2.43 Hz, 1H), 7.24 (t,
Yield: 66%; 1H NMR (CDCl3)
d = 1.00–1.09 (m, 1H), 1.14–1.18
(m, 1H), 1.28–1.40 (m, 2H), 1.41 (t, J = 7.19 Hz, 3H), 1.61–1.66 (m,
2H), 2.00 (br s, 1H), 2.49 (d, J = 5.20 Hz, 1H), 2.61 (br s, 1H), 3.05–
3.08 (m, 1H), 4.41 (q, J = 7.19 Hz, 2H), 7.40 (d, J = 8.19 Hz, 2H), 8.13
J = 8.01 Hz, 1H); 19F NMR (CDCl3)
d
= À60.57 (s, 3F).
(d, J = 8.19 Hz, 2H); 13C NMR (CDCl3)
d
= 14.39, 28.40, 28.99, 31.58,
4.2.9. 2-Trifluoromethyl-3-(4-methoxybenzyl)-3a,4,5,6,7,7a-
hexahydro-4,7-methanoinden-1-one
38.01, 39.84, 53.34, 54.45, 61.47, 121.19 (q, J = 273.05 Hz), 127.14
(m), 129.75, 132.12, 133.67 (q, J = 31.12 Hz), 138.31, 165.81,
Yield: 57% (Combined yield); 1H NMR (CDCl3)
d = 1.02–1.08 (m,
177.77 (q, J = 3.05 Hz), 203.29; 19F NMR (CDCl3)
d
= À60.51 (s, 3F);
IR (neat) 2962, 2876, 1719, 1644, 1608, 1406, 1365, 1276, 1188,
1130, 1020 cmÀ1 HRMS (FAB+) Calcd for (M+) C20H19F3O3:
2H), 1.20–1.26 (m, 2H), 1.55–1.69 (m, 2H), 2.21 (d, J = 5.53 Hz, 1H),
2.36 (d, J = 4.11 Hz, 1H), 2.49 (d, J = 3.74 Hz, 1H), 2.55 (d,
J = 3.33 Hz, 1H), 3.61 (d, J = 14.46 Hz, 1H), 3.80 (s, 3H), 4.25 (d,
J = 14.46 Hz, 1H), 6.86–6.89 (m, 2H), 7.10–7.12 (m, 2H); 13C NMR
;
364.1286, Found 364.1288.
(CDCl3)
d = 28.20, 29.06, 31.56, 35.19, 38.08, 39.26, 50.47, 54.13,
4.2.4. 2-(4-Ethoxycarbonylphenyl)-3-trifluoromethyl-3a,4,5,6,7,7a-
55.25, 114.41, 121.94 (q, J = 273.42 Hz), 127.55, 129.95, 132.63 (q,
J = 30.56 Hz), 158.80, 181.70 (q, J = 1.89 Hz), 203.87; 19F NMR
hexahydro-4,7-methanoinden-1-one (5b)
Yield: 25%; 1H NMR (CDCl3)
d
= 1.12–1.22 (m, 2H), 1.34–1.48
(CDCl3)
d
= À60.81 (s, 3F); IR (neat) 2959, 2876, 2839, 1717, 1639,
(m, 2H), 1.39 (t, J = 7.19 Hz, 3H), 1.60–1.70 (m, 1H), 1.74–1.84 (m,
1H), 2.49 (d, J = 5.60 Hz, 1H), 2.58 (br s, 2H), 2.97 (d, J = 5.99 Hz,
1H), 4.39 (q, J = 7.19 Hz, 2H), 7.31 (d, J = 7.99 Hz, 2H), 8.08 (d,
1611, 1512, 1456, 1421, 1364, 1303, 1252, 1126, 1036 cmÀ1; HRMS
(FAB+) Calcd for (M+H) C19H20F3O2: 337.1415, Found 337.1416.
J = 7.99 Hz, 2H); 13C NMR (CDCl3)
d
= 14.43, 28.34, 29.15, 31.47,
4.2.10. 3-Ethoxycarbonyl-2-trifluoromethyl-3a,4,5,6,7,7a-
hexahydro-4,7-methanoinden-1-one
38.34, 40.29, 47.51, 53.86, 61.26, 122.63 (q, J = 274.13 Hz), 128.99
(m), 129.40, 131.13, 133.74, 148.18 (q, J = 3.31 Hz), 156.16 (q,
Yield: 69%; 1H NMR (CDCl3)
d = 1.11–1.16 (m, 2H), 1.29–1.38
J = 32.23 Hz), 166.21, 207.21; 19F NMR (CDCl3)
(neat) 2963, 2876, 1721, 1609, 1456, 1407, 1367, 1276, 1176, 1109,
1023 cmÀ1; HRMS (FAB+) Calcd for (M+) C20H19F3O3: 364.1286,
Found 364.1291.
d
= À60.64 (s, 3F); IR
(m, 2H), 1.35 (t, J = 7.14 Hz, 3H), 1.59–1.65 (m, 1H), 1.70–1.77 (m,
1H), 2.39 (d, J = 5.38 Hz, 1H), 2.46 (d, J = 4.26 Hz, 1H), 2.54 (d,
J = 3.89 Hz, 1H), 2.95 (br d, J = 2.86 Hz, 1H), 4.37 (q, J = 7.14 Hz, 2H);
13C NMR (CDCl3)
d
= 13.91, 28.06, 28.76, 31.51, 37.85, 39.93, 49.75,
54.02, 62.55, 120.07 (q, J = 272.92 Hz), 134.28 (q, J = 32.95 Hz),
164.48, 167.05 (q, J = 3.14 Hz), 202.41; 19F NMR (CDCl3)
4.2.5. 2-Trifluoromethyl-3-(4-methoxyphenyl)-3a,4,5,6,7,7a-
hexahydro-4,7-methanoinden-1-one
d
= À63.22
(s, 3F); IR (neat) 3432, 2963, 2879, 1730, 1663, 1458, 1374, 1356,
1272, 1189, 1143, 1018, 988, 964, 943 cmÀ1; HRMS (FAB+) Calcd
for (M+H) C14H16F3O3: 289.1052, Found 289.1039.
Yield: 64%; 1H NMR (CDCl3)
d = 0.99 (d, J = 10.75 Hz, 1H), 1.08
(d, J = 10.75 Hz, 1H), 1.35 (d, J = 11.22 Hz, 2H), 1.62 (d, J = 8.93 Hz,
2H), 1.99 (s, 1H), 2.44 (d, J = 5.56 Hz, 1H), 2.56 (s, 1H), 3.12 (d,
J = 3.34 Hz, 1H), 3.86 (s, 3H), 6.99 (d, J = 8.71 Hz, 2H), 7.39 (d,
4.2.11. 2-Difluoromethyl-3-(4-methoxyphenyl)-3a,4,5,6,7,7a-
J = 8.71 Hz, 2H); 13C NMR (CDCl3)
d
= 28.44, 28.89, 31.53, 38.70,
hexahydro-4,7-methanoinden-1-one (4i)
39.52, 52.41, 54.20, 55.36, 113.94, 121.65 (q, J = 273.55 Hz),
125.67, 129.80, 130.83 (q, J = 31.07 Hz), 161.77, 178.33 (q,
Yield: 24%; 1H NMR (CDCl3)
d = 0.98 (d, J = 10.79 Hz, 1H), 1.10
(d, J = 10.79 Hz, 1H), 1.30–1.50 (m, 2H), 1.60–1.80 (m, 2H), 2.01 (br
s, 1H), 2.41 (d, J = 5.60 Hz, 1H), 2.53 (br s, 1H), 3.18 (br s, 1H), 3.87
(s, 3H), 6.48 (t, J = 54.52 Hz, 1H), 6.99 (d, J = 8.79 Hz, 2H), 7.60 (d,
J = 2.77 Hz), 203.57; 19F NMR (CDCl3)
2961, 2876, 2843, 1713, 1605, 1572, 1514, 1458, 1421, 1367, 1298,
1261, 1238, 1180, 1115, 1067, 1030 cmÀ1; HRMS (FAB+) Calcd for
(M+H) C18H18F3O2: 323.1259, Found 323.1269.
d
= À60.24 (s, 3F); IR (neat)
J = 8.79 Hz, 2H); 13C NMR (CDCl3)
d = 28.83, 29.14, 31.77, 39.12,
39.39, 51.44, 54.17, 55.59, 110.88 (t, J = 235.14 Hz), 114.33, 125.59
(m), 130.92 (m), 133.25 (t, J = 21.94 Hz), 162.27, 176.55 (m), 206.75
4.2.6. 3-Trifluoromethyl-2-(4-methoxyphenyl)-3a,4,5,6,7,7a-
hexahydro-4,7-methanoinden-1-one
(m); 19F NMR (CDCl3)
d
= À123.71 (dd, J = 314.75, 54.52 Hz, 1F),
À110.19 (dd, J = 314.75, 54.52 Hz, 1F); IR (neat) 2959, 2874, 2862,
Yield: 26%; 1H NMR (CDCl3)
d
= 1.10–1.18 (m, 2H), 1.34–1.44
1697, 1604, 1514, 1413, 1312, 1294, 1260, 1183, 1107, 1028 cmÀ1
;
(m, 2H), 1.59–1.68 (m, 1H), 1.75–1.80 (m, 1H), 2.44 (d, J = 5.39 Hz,
1H), 2.54 (br s, 2H), 2.92 (d, J = 5.42 Hz, 1H), 3.84 (s, 3H), 6.92–6.95
(m, 2H), 7.21–7.24 (m, 2H).
HRMS (FAB+) Calcd for (M+) C18H18F2O2: 304.1275, Found
304.1268.
4.2.12. 3-Difluoromethyl-2-(4-methoxyphenyl)-3a,4,5,6,7,7a-
4.2.7. 2-Trifluoromethyl-3-(3-methoxyphenyl)-3a,4,5,6,7,7a-
hexahydro-4,7-methanoinden-1-one
hexahydro-4,7-methanoinden-1-one (5i)
Yield: 53%; 1H NMR (CDCl3)
d = 1.00–1.20 (m, 2H), 1.30–1.48
Yield: 59%; 1H NMR (CDCl3)
d
= 0.96 (d, J = 10.81 Hz, 1H), 1.07
(m, 2H), 1.56–1.68 (m, 1H), 1.70–1.80 (m, 1H), 2.40
(d, J = 5.60 Hz, 1H), 2.52 (m, 1H), 2.64 (br s, 1H), 2.96 (m, 1H),
3.83 (s, 3H), 6.47 (t, J = 54.85 Hz, 1H), 6.95 (d, J = 8.79 Hz, 2H),
7.26 (d, J = 8.79 Hz, 2H); 13C NMR (CDCl3)
(d, J = 10.81 Hz, 1H), 1.20–1.32 (m, 2H), 1.53–1.60 (m, 2H), 1.98 (br
s, 1H), 2.38 (d, J = 5.50 Hz, 1H), 2.51 (br s, 1H), 2.98 (d, J = 3.12 Hz,
1H), 3.77 (s, 3H), 6.79 (br s, 1H), 6.85 (d, J = 7.99 Hz, 1H), 6.93 (dd,
J = 7.99, 2.52 Hz, 1H), 7.30 (t, J = 7.99 Hz, 1H); 13C NMR (CDCl3)
d
= 28.53, 29.21, 31.52,
38.43, 40.03, 45.86 (m), 53.85, 55.43, 112.50 (t, J = 235.14 Hz),

T. Konno et al. / Journal of Fluorine Chemistry 144 (2012) 147–156
153
114.22, 121.25, 130.57, 147.48 (t, J = 9.09 Hz), 158.50–
159.10 (m), 160.50, 208.97; 19F NMR (CDCl3)
J = 326.98, 54.85 Hz), À110.81 (dd, J = 326.98, 54.85 Hz); IR
(neat) 2957, 2874, 2839, 1712, 1608, 1513, 1458, 1385, 1292,
1254, 1180, 1095, 1028 cmÀ1; HRMS (FAB+) Calcd for (M+)
4.3.4. 1-Cyclohexyl-4,4,4-trifluoro-2-butyn-1-ol (8c)
Yield: quant.; 1H NMR (CDCl3)
= 1.01–1.34 (m, 6H), 1.58–
1.66 (m, 1H), 1.66–1.72 (m, 4H), 3.22 (br s, 1H), 4.23 (ddq,
J = 3.08, 3.18, 3.08 Hz, 1H); 13C NMR (CDCl3)
= 25.58, 25.60,
26.07, 27.92, 28.32, 43.40, 66.46, 72.77 (q, J = 52.80 Hz), 87.21 (q,
J = 6.31 Hz), 114.06 (q, J = 257.07 Hz); 19F NMR (CDCl3)
d
= À119.73 (dd,
d
d
C
18H18F2O2: 304.1275, Found 304.1278.
d
= À50.73 (s, 3F); IR (neat) 3612, 3334, 2926, 2857, 2674,
4.2.13. 2-Trifluoromethyl-3-(4-chlorophenyl)-3a,4,7,7a-tetrahydro-
2275, 1452, 1402, 1278, 1140, 1085, 1038, 999 cmÀ1; MS (EI+)
m/z (rel. intensity) 123 (M-C6H11, 89.40), 83 (M-C4H2F3O, 100.0),
58 (100.0).
4,7-methanoinden-1-one (4j)
Yield: 68% (Combined yield); 1H NMR (CDCl3)
d
= 1.20–1.60 (m,
2H), 2.40–2.60 (m, 2H), 3.00–3.30 (m, 2H), 6.15–6.40 (m, 2H),
7.20–7.60 (m, 4H); 13C NMR (CDCl3)
= 41.69, 43.27, 44.44, 52.92,
d
4.3.5. 5-Ethyl-1,1,1-trifluoro-2-heptyn-4-ol (8d)
53.36, 120.92 (q, J = 273.32 Hz), 128.69, 129.09, 132.09, 133.07 (q,
J = 31.12 Hz), 136.98, 138.07, 138.29, 177.58, 201.87; 19F NMR
Yield: 99%; 1H NMR (CDCl3)
d
= 0.93 (t, J = 7.37 Hz, 3H), 0.94 (t,
J = 7.41 Hz, 3H), 1.35–1.43 (m, 1H), 1.45–1.53 (m, 3H), 1.54–1.62
(m, 1H), 2.87 (br s, 1H), 4.49 (ddq, J = 5.05, 5.05, 2.48 Hz, 1H); 13
NMR (CDCl3) = 11.07, 11.22, 21.59, 21.72, 46.79, 64.07, 72.77 (q,
J = 52.63 Hz), 87.42 (q, J = 6.40 Hz), 114.07 (q, J = 257.45 Hz); 19F
NMR (CDCl3)
(CDCl3)
d
= À60.58 (s, 3F); IR (neat) 3080, 2989, 2951, 2882, 1710,
C
1615, 1592, 1492, 1362, 1327, 1308, 1196, 1058, 1014 cmÀ1
;
d
HRMS (FAB+) Calcd for (M+) C17H12ClF3: 324.0529, Found
324.0524.
d
= À50.82 (s, 3F); IR (neat) 3614, 3346, 2969, 2882,
2744, 2548, 2424, 2257, 1713, 1611, 1464, 1385, 1275, 1140, 1028,
941 cmÀ1; HRMS (EI+) Calcd for (M+) C9H13F3O: 194.0918, Found
194.0914.
4.2.14. 3-Trifluoromethyl-2-(4-chlorophenyl)-3a,4,7,7a-tetrahydro-
4,7-methanoinden-1-one (5j)
19F NMR (CDCl3)
d
= À61.41 (s, 3F).
4.3.6. 1-Trifluoropropynylcyclohexanol (8e)
4.3. Preparation of fluorine-containing propargyl alcohol 7
Yield: 96%; 1H NMR (CDCl3)
d
= 1.23–1.32 (m, 1H), 1.47–1.59
(m, 3H), 1.60–1.67 (m, 2H), 1.70–1.77 (m, 2H), 1.92–1.98 (m, 2H),
2.33 (s, 1H); 13C NMR (CDCl3)
= 22.71, 24.73, 38.85, 68.35, 71.56
(q, J = 52.58 Hz), 90.62 (q, J = 6.28 Hz), 114.19 (q, J = 257.20 Hz);
19F NMR (CDCl3)
To a solution of diisopropylamine (4.20 mL, 30 mmol) in THF
(100 mL) was added 1.6 M n-BuLi solution in hexane (18.75 mL,
30 mmol) at À78 8C and the whole was stirred for 20 min. To this
solution was added 2-bromo-3,3,3-trifluoropropene (1.50 mL,
15 mmol) very slowly. After stirring at À78 8C for 20 min,
various aldehydes (10 mmol) or ketones (10 mmol) were added
to the solution and the whole was stirred for 1 h at À78 8C. The
reaction mixture was quenched with saturated NH4Cl aq. and
extracted with ethyl acetate three times. The combined organic
layers were dried over anhydrous Na2SO4 and concentrated in
vacuo. The residue was chromatographed on silica gel to afford
fluorine-containing propargyl alcohols 7 and 8.
d
d
= À50.58 (s, 3F); IR (KBr) 3251, 2948, 2868,
2280, 2250, 1454, 1347, 1298, 1267, 1218, 1141, 1076, 1033,
969 cmÀ1; HRMS (EI+) Calcd for (MÀH) C9H10F3O: 191.0684,
Found 191.0669.
4.4. Preparation of difluoromethyl-containing propargyl alcohol
To a solution of 2,3,3-trifluoro-1-iodopropene (3.3 g, 15 mmol)
in THF (100 mL) was added 1.6 M n-BuLi hexane solution
(18.75 mL, 30 mmol) at À78 8C. After stirring for 1 h, n-heptanal
(1.39 mL, 10 mmol) was added to the solution at À78 8C and the
whole was stirred for 1 h. The reaction mixture was quenched
with saturated NH4Cl aq. and extracted with ethyl acetate three
times. The combined organic layers were dried over anhydrous
Na2SO4 and concentrated in vacuo. The residue was chromato-
graphed on silica gel to afford fluorine-containing propargyl
alcohol 8f.
4.3.1. 1,1,1-Trifluoro-5,5-dimethyl-7-octen-2-yn-4-ol (7a)
Yield: 73%; 1H NMR (CDCl3)
d
= 1.00 (s, 3H), 1.02 (s, 3H), 2.04–
2.22 (m, 3H), 4.18–4.22 (m, 1H), 5.10–5.13 (m, 2H), 5.78–5.87 (m,
1H); 13C NMR (CDCl3)
= 22.46, 22.61, 38.72, 42.62, 69.38, 73.40
(q, J = 52.43 Hz), 86.94 (q, J = 21.88 Hz), 114.01 (q, J = 257.30 Hz),
118.55, 134.00; 19F NMR (CDCl3)
d
d
= À56.76 (s, 3F); IR (neat) 3400,
2968, 2878, 2251, 1641, 1472, 1369, 1275, 1148, 1053, 1003,
920 cmÀ1; HRMS (EI+) Calcd for (MÀH) C10H12F3O: 205.0840,
Found 205.0845.
4.4.1. 1,1-Difluoro-2-decyn-4-ol (8f)
Yield: 98%; 1H NMR (CDCl3)
d = 0.87 (t, J = 7.00 Hz, 3H), 1.24–
1.34 (m, 6H), 1.39–1.45 (m, 2H), 1.67–1.78 (m, 2H), 3.20 (br s, 1H),
4.3.2. 1,1,1-Trifluoro-2-decyn-4-ol (8a)
4.42 (ddt, J = 4.87, 4.87, 6.02 Hz, 1H), 6.19 (td, J = 55.42, 0.76 Hz,
Yield: quant.; 1H NMR (CDCl3)
d
= 0.89 (t, J = 6.94 Hz, 3H), 1.25–
1.36 (m, 6H), 1.40–1.48 (m, 2H), 1.71–1.81 (m, 2H), 2.84 (br s, 1H),
4.45 (ddq, J = 3.29, 3.29, 3.29 Hz, 1H); 13C NMR (CDCl3)
= 13.90,
1H); 13C NMR (CDCl3)
d
= 13.91, 22.48, 24.83, 28.76, 31.59, 36.88,
61.85, 75.79 (t, J = 33.98 Hz), 89.88 (t, J = 7.29 Hz), 103.60 (t,
J = 232.05 Hz); 19F NMR (CDCl3)
d
d
= À106.38 (dd, J = 55.42, 4.89 Hz,
22.50, 24.76, 28.72, 31.58, 36.65, 61.79, 72.02 (q, J = 52.85 Hz),
87.91 (q, J = 6.18 Hz), 114.07 (q, J = 257.45 Hz); 19F NMR (CDCl3)
2F); IR (neat) 3603, 3354, 2929, 2861, 2314, 2253, 1713, 1467,
1372, 1340, 1156, 1121, 1047 cmÀ1; HRMS (EI+) Calcd for (MÀH)
d
= À50.94 (s, 3F); IR (neat) 3330, 2933, 2862, 2271, 1468, 1381,
C10H15F2O: 189.1091, Found 189.1085.
1275, 1220, 1144, 1046 cmÀ1
.
4.5. Preparation of fluorine-containing propargyl acetate (7b)
4.3.3. 6,6,6-Trifluoro-1-phenyl-4-hexyn-3-ol (8b)
Yield: 80%; 1H NMR (CDCl3)
= 2.11–2.23 (m, 2H), 2.89 (t,
J = 7.72 Hz, 2H), 3.35 (br s, 1H), 4.48 (br s, 1H), 7.29–7.35 (m, 3H),
7.40–7.43 (m, 2H); 13C NMR (CDCl3)
= 30.88, 37.87, 60.72, 72.20
(q, J = 52.95 Hz), 87.64 (q, J = 6.36 Hz), 114.05 (q, J = 257.33 Hz),
126.29, 128.38, 128.56, 140.21; 19F NMR (CDCl3)
IR (neat) 3366, 3088, 3066, 3030, 2956, 2931, 2866, 2269, 1710,
1604, 1497, 1455, 1379, 1275, 1140, 1049, 1017, 915 cmÀ1; HRMS
(FAB+) Calcd for (M+) C12H11F3O: 228.0762, Found 228.0765.
d
To a solution of 7a (1.03 g, 5.0 mmol) in CH2Cl2 (25 mL)
was added pyridine (0.81 mL, 10 mmol) and acetic anhydride
(0.95 mL, 10 mmol) at 0 8C and the whole was stirred for 12 h at
r.t. The reaction mixture was quenched with saturated NH4Cl aq.
and extracted with CH2Cl2 three times. The combined organic
layers were dried over anhydrous Na2SO4 and concentrated in
vacuo. The residue was chromatographed on silica gel to
afford fluorine-containing acetate 7b (1.10 g, 4.45 mmol).
d
d
= À50.78 (s, 3F);

154
T. Konno et al. / Journal of Fluorine Chemistry 144 (2012) 147–156
4.5.1. 2,2-Dimethyl-1-trifluoropropynyl-4-pentenyl acetate (7b)
Yield: 89%; 1H NMR (CDCl3)
= 1.02 (s, 3H), 1.03 (s, 3H), 2.13
(s, 5H), 4.95–5.15 (m, 2H), 5.21 (q, J = 2.91 Hz, 1H), 5.72–5.81 (m,
1H); 13C NMR (CDCl3)
= 20.57, 22.57, 22.85, 37.87, 42.73, 69.05,
73.16 (q, J = 52.68 Hz), 83.61 (q, J = 6.43 Hz), 113.82 (q,
J = 257.81 Hz), 118.82, 133.05, 169.51; 19F NMR (CDCl3)
(q, J = 52.41 Hz), 86.47 (q, J = 6.28 Hz), 114.02 (q, J = 257.33 Hz),
d
118.07, 126.22, 128.46, 128.52, 133.51, 140.49; 19F NMR (CDCl3)
d
= À50.66 (s, 3F); IR (neat) 3030, 2930, 2866, 2264, 1497, 1456,
d
1427, 1277, 1144, 1096, 1061, 995, 932 cmÀ1; HRMS (EI+) Calcd for
(M+) C15H15F3O: 268.1075, Found 268.1062.
d
= À50.98 (s, 3F); IR (neat) 2974, 2935, 2882, 2438, 2266, 1751,
4.7.3. 1-Allyloxy-1-cyclohexyl-4,4,4-trifluoro-2-butyne (9c)
1716, 1641, 1421, 1364, 1283, 1229, 1150, 1092, 1022, 906 cmÀ1
.
Yield: 91%; 1H NMR (CDCl3)
d = 1.04–1.30 (m, 5H), 1.66–1.87
(m, 6H), 3.91–3.96 (m, 2H), 4.23 (ddt, J = 12.64, 5.03, 1.44 Hz, 1H),
5.21 (ddt, J = 10.40, 1.38, 1.19 Hz, 1H), 5.31 (ddt, J = 17.24, 1.57,
4.6. Preparation of fluorine-containing propargyl silyl ether (7c)
1.54 Hz, 1H), 5.84–5.91 (m, 1H); 13C NMR (CDCl3)
d
= 25.70, 25.74,
26.19, 28.31, 28.68, 42.14, 70.45, 72.89, 73.56 (q, J = 52.31 Hz),
86.10 (q, J = 6.35 Hz), 114.05 (q, J = 257.33 Hz), 117.89, 133.69; 19
NMR (CDCl3)
= À50.51 (s, 3F); IR (neat) 3437, 3085, 3018, 2926,
2857, 2666, 2254, 1736, 1649, 1453, 1424, 1411, 1374, 1332, 1279,
1215, 1140, 998 cmÀ1
To
a solution of imidazole (511 mg, 7.50 mmol) and t-
butyldimethylsilyl chloride, TBSCl (453 mg, 3.00 mmol) in DMF
(7.50 mL) was added 7a (309 mg, 1.50 mmol) at r.t. and the whole
was stirred for 10 h at 70 8C. The reaction mixture was quenched
with saturated NH4Cl aq. and extracted with diethyl ether three
times. The combined organic layers were dried over anhydrous
Na2SO4 and concentrated in vacuo. The residue was chromato-
graphed on silica gel to afford fluorine-containing acetate 7c
(333 mg, 1.04 mmol).
F
d
.
4.7.4. 4-Allyloxy-5-ethyl-1,1,1-trifluoro-2-heptyne (9d)
Yield: 98%; 1H NMR (CDCl3)
= 0.91 (t, J = 7.40 Hz, 3H), 0.92 (t,
d
J = 7.41 Hz, 3H), 1.35–1.42 (m, 1H), 1.46–1.51 (m, 2H), 1.56–1.64
(m, 2H), 3.94 (ddt, J = 12.66, 6.41, 1.27 Hz, 1H), 4.17 (ddq, J = 2.91,
2.21, 2.91 Hz, 1H), 4.24 (ddt, J = 12.64, 4.99, 1.57 Hz, 1H), 5.23 (ddt,
J = 10.40, 1.29, 1.38 Hz, 1H), 5.32 (ddt, J = 17.23, 1.57, 1.57 Hz, 1H),
4.6.1. 4-(tert-Butyldimethylsilyloxy)-1,1,1-trifluoro-5,5-dimethyl-7-
octen-2-yne (7c)
Yield: 69%; 1H NMR (CDCl3)
d
= 0.10 (s, 3H), 0.15 (s, 3H), 0.92 (s,
5.85–5.93 (m, 1H); 13C NMR (CDCl3)
d = 11.32, 11.41, 21.99, 22.06,
9H), 0.94 (s, 3H), 0.96 (s, 3H), 2.00–2.20 (m, 2H), 4.10 (q, J = 3.06 Hz,
1H), 5.00–5.15 (m, 2H), 5.70–5.90 (m, 1H); 13C NMR (CDCl3)
45.58, 70.50, 70.59, 73.55 (q, J = 52.53 Hz), 86,36 (q, J = 6.38 Hz),
114.02 (q, J = 256.95 Hz), 117.93, 133.72; 19F NMR (CDCl3)
d
= À5.34, À4.68, À2.96, 18.10, 22.40, 22.55, 25,62, 25.69, 39.23,
42.40, 69.86, 73.00 (q, J = 52.30 Hz), 88.07 (q, J = 6.41 Hz), 114.10
(q, J = 257.43 Hz), 117.99, 134.18; 19F NMR (CDCl3)
d
= À50.54 (s, 3F); IR (neat) 3086, 2967, 2939, 2880, 2261, 1736,
1649, 1463, 1424, 1412, 1383, 1330, 1275, 1215, 1143, 1078,
998 cmÀ1; HRMS (FAB+) Calcd for (M-H) C12H16F3O: 233.1153,
Found 233.1160.
d
= À50.85 (s,
3F); IR (neat) 2960, 2932, 2860, 2251, 2141, 1717, 1420, 1364,
1277, 1221, 1146, 1094, 1007, 901 cmÀ1; MS (EI+) m/z (rel.
intensity) 263 (MÀC4H9, 100.0).
4.7.5. 1-Allyloxy-1-trifluoropropynylcyclohexane (9e)
Yield: 51%; 1H NMR (CDCl3)
d
= 1.35–2.05 (m, 10H), 4.09 (dt,
J = 5.46, 1.14 Hz, 2H), 5.15–5.21 (m, 1H), 5.31 (dd, J = 17.20,
1.60 Hz, 1H), 5.90–5.98 (m, 1H); 13C NMR (CDCl3)
= 22.31, 25.04,
4.7. Preparation of fluorine-containing allyl propargyl ether 9
d
To a solution of NaH (36 mg, 0.75 mmol) in THF (1.25 mL) was
added dimethylpropylene urea (DMPU) (0.24 mL, 2.00 mmol), 8
(0.50 mmol), and allyl bromide (0.17 mL, 2.00 mmol) at–78 8C. The
whole was stirred for 5 min. at À78 8C followed by warming up to
r.t. After stirring for 20 min at r.t., the reaction mixture was
quenched with saturated NH4Cl aq. and extracted with ethyl
acetate three times. The combined organic layers were dried over
anhydrous Na2SO4 and concentrated in vacuo. The residue was
chromatographed on silica gel to afford fluorine-containing allyl
propargyl ether 9.
36.26, 64.96, 73.14 (q, J = 52.51 Hz), 73.21, 89.00 (q, J = 6.34 Hz),
114.18 (q, J = 256.95 Hz), 116.64, 134.64; 19F NMR (CDCl3)
d
= À50.35 (s, 3F); IR (neat) 3084, 2940, 2864, 2270, 1729, 1693,
1681, 1648, 1451, 1426, 1385, 1353, 1264, 1140, 1030, 995 cmÀ1
.
4.7.6. 4-Allyloxy-1,1-difluoro-2-decyne (9f)
Yield: 56%; 1H NMR (CDCl3)
d = 0.88 (t, J = 6.92 Hz, 3H), 1.25–
1.33 (m, 6H), 1.40–1.47 (m, 2H), 1.69–1.81 (m, 2H), 3.95 (dd,
J = 12.53, 6.32 Hz, 1H), 4.14 (tdd, J = 5.97, 4.95, 4.95 Hz, 1H), 4.22
(dd, J = 12.56, 5.09 Hz, 1H), 5.20 (d, J = 10.39 Hz, 1H), 5.30 (dd,
J = 17.23, 1.36 Hz, 1H), 5.85–5.92 (m, 1H), 6.21 (t, J = 55.42 Hz, 1H);
4.7.1. 4-Allyloxy-1,1,1-trifluoro-2-decyne (9a)
13C NMR (CDCl3)
(t, J = 1.67 Hz), 70.01, 76.75 (t, J = 33.71 Hz), 88.31 (t, J = 7.19 Hz),
103.55 (t, J = 232.05 Hz), 117.76, 133.83; 19F NMR (CDCl3)
= –
d = 13.94, 22.50, 24.97, 28.83, 31.59, 34.99, 68.27
Yield: 85%; 1H NMR (CDCl3)
d = 0.88 (t, J = 6.99 Hz, 3H), 1.25–
1.34 (m, 6H), 1.40–1.47 (m, 2H), 1.71–1.82 (m, 2H), 3.96 (dd,
J = 12.53 Hz, 6.37 Hz, 1H), 4.15 (ddq, J = 6.57, 6.57, 3.13 Hz, 1H),
4.22 (ddt, J = 12.52, 5.11, 1.30 Hz, 1H), 5.23 (dd, J = 10.38, 1.21 Hz,
1H), 5.31 (ddt, J = 17.21, 1.51, 1.38 Hz, 1H), 5.85–5.93 (m, 1H); 13
d
106.15 (dd, J = 55.42, 4.51 Hz, 2F); IR (neat) 3435, 3084, 2930,
2861, 2251, 1732, 1648, 1460, 1426, 1410, 1373, 1336, 1272, 1155,
C
1047, 931 cmÀ1
229.1404, Found 229.1413.
;
HRMS (FAB+) Calcd for (MÀH) C13H19F2O:
NMR (CDCl3)
70.31, 72.78 (q, J = 52.42 Hz), 86.76 (q, J = 6.41 Hz), 114.02 (q,
J = 257.07 Hz), 118.07, 133.60; 19F NMR (CDCl3)
d
= 13.94, 22.51, 24.91, 28.81, 31.59, 34.76, 68.03,
d
= À50.68 (s, 3F);
4.8. General procedure for the intramolecular Pauson–Khand reaction
IR (neat) 3086, 2931, 2861, 2268, 1736, 1649, 1460, 1423, 1379,
1337, 1276, 1147, 1091, 995 cmÀ1; HRMS (FAB+) Calcd for (MÀH)
To a solution of Co2(CO)8 (68 mg, 0.20 mmol) in THF (2.00 mL)
was added fluorine-containing enynes 7a–c or allyl propargyl
ethers 9 (0.20 mmol) at r.t. After stirring for 1 h at r.t. the reaction
mixture was cooled to 0 8C. To the solution was added N-
methylmorpholine N-oxide, NMO (1.5, 3.0, or 6.0 equiv.) or
trimethylamine N-oxide dihydrate, TMANOÁ2H2O (1.5, 3.0, or
6.0 equiv.) at 0 8C. Then the whole was stirred for 1 h at r.t. The
reaction mixture was quenched with saturated NH4Cl aq. and
NaCl aq. and extracted with ethyl acetate three times. The
combined organic layers were dried over anhydrous Na2SO4 and
C
13H18F3O: 247.1310, Found 247.1299.
4.7.2. 4-Allyloxy-1,1,1-trifluoro-6-phenyl-2-hexyne (9b)
Yield: 67%; 1H NMR (CDCl3)
= 2.13–2.20 (m, 1H), 2.22–2.29
d
(m, 1H), 2.90 (t, J = 7.60 Hz, 2H), 4.04 (dddt, J = 12.48, 6.28, 1.21,
1.21 Hz, 1H), 4.19–4.23 (m, 1H), 4.34 (dddt, J = 12.43, 5.16, 1.38,
1.43 Hz, 1H), 5.34 (dt, J = 10.38, 1.13 Hz, 1H), 5.44 (dt, J = 17.18,
1.49 Hz, 1H), 5.98–6.05 (m, 1H), 7.28–7.33 (m, 3H), 7.38–7.42
(m, 2H); 13C NMR (CDCl3)
d = 31.04, 36.30, 67.06, 70.39, 73.08

T. Konno et al. / Journal of Fluorine Chemistry 144 (2012) 147–156
155
concentrated in vacuo. The residue was chromatographed on silica
gel to afford cyclopentenone derivatives 11a–c, 12a–e.
1H NMR (CDCl3)
d = 0.02 (s, 3H), 0.12 (s, 3H), 0.84 (s, 3H), 0.88 (s,
9H), 1.16 (s, 3H), 1.16 (dd, J = 13.03, 6.32 Hz, 1H), 2.04–2.20 (m,
2H), 2.85 (dd, J = 18.29, 7.07 Hz, 1H), 3.43–3.49 (m, 1H), 4.35 (s,
1H); 13C NMR (CDCl3)
d = 0.99, 14.09, 18.08, 22.63, 23.77, 25.62,
28.33, 31.57, 39.80, 41.62, 44.87, 45.13, 76.06, 121.16 (q,
J = 272.02 Hz), 125.74 (q, J = 32.95 Hz), 189.22 (q, J = 2.89 Hz),
4.8.1. 3-Trifluoromethyl-4-hydroxy-5,5-dimethyl-4,5,6,6a-
tetrahydro-2(1H)-pentalenone (11a)
Yield: 67%.
203.12; 19F NMR (CDCl3)
d
= À62.54 (s, 3F); IR (neat) 2957, 2932,
2860, 1732, 1684, 1472, 1362, 1344, 1261, 1230, 1215, 1140, 1094,
939 cmÀ1 HRMS (FAB+) Calcd for (M+H) C17H28F3O228Si:
Major isomer
;
1H NMR (CDCl3)
d = 1.08 (s, 3H), 1.20 (s, 3H), 1.46 (dd, J = 12.51,
349.1811, Found 349.1802.
11.09 Hz, 1H), 1.97–2.04 (m, 1H), 2.24 (br s, 1H), 2.24 (dd, J = 17.97,
3.82 Hz, 1H), 2.78 (d, J = 17.96, 6.80 Hz, 1H), 3.10–3.16 (m, 1H),
Minor isomer
4.61 (s, 1H); 13C NMR (CDCl3)
d
= 23.61, 28.25, 39.98, 42.75, 43.43,
44.87, 75.51, 121.26 (q, J = 271.64 Hz), 127.88 (q, J = 33.58 Hz),
192.50 (q, J = 2.52 Hz), 201.95; 19F NMR (CDCl3)
1H NMR (CDCl3)
d = 0.07 (s, 3H), 0.12 (s, 3H), 0.89 (s, 3H), 0.94 (s,
9H), 1.19 (s, 3H), 1.40 (dd, J = 13.50, 7.75 Hz, 1H), 2.04–2.15 (m,
2H), 2.76 (dd, J = 18.09, 7.25 Hz, 1H), 3.00–3.06 (m, 1H), 4.72 (d,
J = 1.66 Hz, 1H); 13C NMR (CDCl3)
d
= À60.99 (s, 3F);
IR (neat) 3447, 2962, 2936, 2872, 1716, 1672, 1360, 1132, 1065,
1011, 941 cmÀ1; HRMS (FAB+) Calcd for (M+H) C11H14F3O2:
235.0946, Found 235.0937.
d = –3.96, 14.10, 18.07, 22.64,
24.22, 25.93, 28.71, 31.57, 35.89, 42.25, 44.07, 44.41, 80.18, 121.04
(q, J = 272.65 Hz), 126.82 (q, J = 34.21 Hz), 190.55 (q, J = 2.64 Hz),
202.27; 19F NMR (CDCl3)
d
= À58.45 (s, 3F); IR (neat) 2957, 2932,
2860, 1732, 1684, 1472, 1362, 1344, 1261, 1230, 1215, 1140, 1094,
939 cmÀ1 HRMS (FAB+) Calcd for (M+H) C17H28F3O228Si:
Minor isomer
1H NMR (CDCl3)
d = 1.05 (s, 3H), 1.19 (s, 3H), 1.25 (dd, J = 8.49,
;
349.1811, Found 349.1818.
7.14 Hz, 1H), 1.97–2.04 (m, 1H), 2.11 (dd, J = 12.80, 9.70 Hz, 1H),
2.23 (br s, 1H), 2.79–2.84 (m, 1H), 3.42–3.47 (m, 1H), 4.51 (s, 1H);
13C NMR (CDCl3)
d
= 22.36, 28.75, 40.94, 42.54, 43.88, 44.55, 75.51,
4.8.4. 1-Hexyl-6-trifluoromethyl-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one (12a)
121.28 (q, J = 272.02 Hz), 127.62 (q, J = 33.20 Hz), 188.63, 202.55;
Yield: 34%; 1H NMR (CDCl3)
d = 0.87 (t, J = 6.86 Hz, 3H), 1.24–
19F NMR (CDCl3)
d
= À62.54 (s, 3F); IR (neat) 3447, 2962, 2936,
2872, 1716, 1672, 1360, 1132, 1065, 1011, 941 cmÀ1; HRMS (FAB+)
Calcd for (M+H) C11H14F3O2: 235.0946, Found 235.0937.
1.48 (m, 8H), 1.68–1.83 (m, 2H), 2.28 (dd, J = 18.10, 2.92 Hz, 1H),
2.71–2.78 (m, 1H), 3.31–3.39 (m, 2H), 4.36–4.43 (m, 1H), 4.83 (br s,
1H); 13C NMR (CDCl3)
d
= 13.96, 22.48, 25.17, 28.90, 31.54, 33.72,
39.52, 44.00, 70.61, 76.38, 121.05 (q, J = 271.41 Hz), 125.95 (q,
J = 34.34 Hz), 188.43, 200.97; 19F NMR (CDCl3)
= À62.33 (s, 3F); IR
(neat) 2955, 2929, 2859, 1734, 1687, 1468, 1370, 1342, 1310, 1205,
1137, 1023, 951, 929 cmÀ1 HRMS (FAB+) Calcd for (M+H)
14H20F3O2: 277.1415, Found 277.1414; Anal. Calcd for
14H19F3O2: C, 60.86; H, 6.93. Found: C, 61.20; H, 6.57.
4.8.2. 4-(Acetyloxy)-3-trifluoromethyl-5,5-dimethyl-4,5,6,6a-
tetrahydro-2(1H)-pentalenone (11b)
Yield: 52%.
d
;
C
C
Major isomer
1H NMR (CDCl3)
d = 1.11 (s, 3H), 1.15 (s, 3H), 1.24 (dd, J = 12.77,
10.47 Hz, 1H), 2.12 (s, 3H), 2.12–2.15 (m, 1H), 2.24 (dd, J = 18.25,
3.48 Hz, 1H), 2.80 (t, J = 7.21 Hz, 1H), 3.35–3.41 (m, 1H), 5.68 (s,
4.8.5. 6-Trifluoromethyl-1-(2-phenylethyl)-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one (12b)
Yield: 45%; 1H NMR (CDCl3)
d = 1.99–2.06 (m, 1H), 2.12–2.19
1H); 13C NMR (CDCl3)
d
= 20.42, 23.12, 28.78, 41.23, 43.22, 44.06,
44.62, 75.60, 120.74 (q, J = 271.39 Hz), 128.44 (q, J = 23.01 Hz),
169.47, 184.23 (q, J = 3.27 Hz), 201.88; 19F NMR (CDCl3)
(m, 1H), 2.29 (dd, J = 18.12, 2.90 Hz, 1H), 2.74–2.84 (m, 3H), 3.34–
3.41 (m, 2H), 4.44 (br s, 1H), 4.82 (br d, J = 8.27 Hz, 1H), 7.20–7.32
d
= À63.10
(m, 5H); 13C NMR (CDCl3)
d = 31.35, 35.18, 39.55, 44.04, 70.70,
(s, 3F); IR (neat) 2968, 2939, 2874, 1732, 1684, 1373, 1317, 1236,
1196, 1134, 1045, 941, 912 cmÀ1; HRMS (FAB+) Calcd for (M+H)
C13H16F3O3: 277.1052, Found 277.1054.
75.52, 120.98 (q, J = 271.39 Hz), 126.06 (q, J = 34.46 Hz), 126.24,
128.41, 128.50, 140.47, 188.04 (q, J = 3.14 Hz), 200.77; 19F NMR
(CDCl3)
d
= À62.32 (s, 3F); IR (neat) 3028, 2862, 1732, 1690, 1497,
1456, 1371, 1344, 1310, 1132, 1030, 991, 949, 928, 912 cmÀ1
;
Minor isomer
HRMS (FAB+) Calcd for (M+H) C16H16F3O2: 297.1102, Found
297.1103.
1H NMR (CDCl3)
d = 1.02 (s, 3H), 1.28 (s, 3H), 1.43 (t,
J = 12.23 Hz, 1H), 2.02 (dd, J = 12.43, 8.11 Hz, 1H), 2.12 (s, 3H),
2.28 (dd, J = 18.18, 3.46 Hz, 1H), 2.84 (t, J = 6.78 Hz, 1H), 3.19–
d = 20.21, 23.56,
27.99, 40.77, 42.82, 43.50, 44.72, 76.21, 120.75 (q, J = 272.65 Hz),
128.71 (q, J = 23.14 Hz), 169.79, 188.45 (q, J = 2.52 Hz), 201.19;
4.8.6. 1-Cyclohexyl-6-trifluoromethyl-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one (12c)
3.24 (m, 1H), 5.82 (s, 1H); 13C NMR (CDCl3)
Yield: 35%; 1H NMR (CDCl3)
d = 1.12–1.32 (m, 5H), 1.58–1.62
(m, 1H), 1.65–1.70 (m, 2H), 1.73–1.80 (m, 3H), 2.27 (dd, J = 17.85,
2.87 Hz, 1H), 2.72–2.78 (m, 1H), 3.28–3.35 (m, 2H), 4.35–4.41 (m,
1H), 4.68 (br s, 1H); 13C NMR (CDCl3)
d = 25.91, 26.20, 27.83, 29.31,
39.60, 41.97, 44.23, 70.35, 80.76, 121.01 (q, J = 271.79 Hz), 126.83
(q, J = 33.96 Hz), 187.42 (q, J = 3.14 Hz), 201.23; 19F NMR (CDCl3)
19F NMR (CDCl3)
d
= À62.11 (s, 3F); IR (neat) 2968, 2939, 2874,
1732, 1684, 1373, 1317, 1236, 1196, 1134, 1045, 941, 912 cmÀ1
;
HRMS (FAB+) Calcd for (M+H) C13H16F3O3: 277.1052, Found
277.1054.
d
= À62.20 (s, 3F); HRMS (FAB+) Calcd for (M+H) C14H18F3O2:
275.1259, Found 275.1269; Anal. Calcd for C14H17F3O2: C, 61.31; H,
6.25. Found: C, 61.07; H, 6.15.
4.8.3. 4-(tert-Butyldimethylsilyloxy)-3-trifluoromethyl-5,5-
dimethyl-4,5,6,6a-tetrahydro-2(1H)-pentalenone (11c)
Yield: 53%.
4.8.7. 1-(1-Ethylpropyl)-6-trifluoromethyl-3a,4-dihydro-1H-
cyclopenta[c]furan-5(3H)-one (12d)
Yield: 51%; 1H NMR (CDCl3)
d
= 0.88 (t, J = 7.49 Hz, 3H), 0.97 (t,
Major isomer
J = 7.44 Hz, 3H), 1.28–1.34 (m, 1H), 1.38–1.45 (m, 2H), 1.50–1.57

156
T. Konno et al. / Journal of Fluorine Chemistry 144 (2012) 147–156
(j) S. Laschat, A. Becheanu, T. Bell, A. Baro, Synlett (2005) 2547–2570;
(k) M. Turlington, Y. Yue, X.-Q. Yu, L. Pu, Journal of Organic Chemistry 75 (2010)
6941–6952.
(m, 1H), 1.67–1.72 (m, 1H), 2.28 (ddd, J = 18.00, 2.89, 0.70 Hz, 1H),
2.72–2.78 (m, 1H), 3.28–3.34 (m, 2H), 4.34–4.40 (m, 1H), 4.88 (br s,
1H); 13C NMR (CDCl3)
d
= 11.55, 22.05, 22.55, 39.76, 44.71, 44.96,
70.22, 78.37, 121.10 (q, J = 271.54 Hz), 126.29 (q, J = 33.83 Hz),
189.40 (q, J = 2.77 Hz), 201.05; 19F NMR (CDCl3)
[4] For preliminary findings, we have already reported. See, The Tenth International
Kyoto Conference on New Aspects of Organic Chemistry (IKCOC-10). Program and
Abstracts, PA-0272006.
[5] For the preparation of the fluorinated alkynes, See
(a) T. Hiyama, K. sato, M. Fujita, Bulletin of the Chemical Society of Japan 62
(1989) 1352–1354;
d
= À62.14 (s, 3F);
IR (neat) 2966, 2937, 2878, 1732, 1682, 1463, 1412, 1368, 1339,
1306, 1286, 1233, 1205, 1136, 1049, 1023, 1000, 953 cmÀ1; HRMS
(EI+) Calcd for C13H17F3O2: 262.1181, Found 262.1192.
(b) T. Konno, J. Chae, M. Kanda, G. Nagai, K. Tamura, T. Ishihara, H. Yamanaka,
Tetrahedron 59 (2003) 7571–7580.
[6] Generally, the intermolecular Pauson–Khand reaction of alkynes with norbornene
as well as norbornadiene yields exclusively the exo-fused cyclopentenone
adducts. Additionally, there has been one example in which the intermolecular
Pauson–Khand reaction of ethyl 4,4,4-trifluorobutynoate with 2,5-norbornadiene
in the presence of Co2(CO)8 afforded the exo-adduct exclusively (see Ref. [2d].)
Therefore, we determined the products 4 and 5 as the exo-adducts. There have
been very few examples of endo-selectivity. See
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