Sodium dithionite initiated regio- and stereoselective radical addition of polyfluoroalkyl iodide with norbornene analogs

Article abstract of DOI:10.1016/j.tet.2006.08.042

Sodium dithionite initiated free-radical addition of polyfluoroalkyl iodides (2m-2s) with norbornene 1a and its derivatives, such as norbornene-2-carboxylates 1b and 1c, and norbornene-2-carboxylic acids 1d and 1e was investigated. In all the cases, the addition of R_F group was stereoselectively delivered at exo-position and the predominant configuration of products was trans. Under the similar condition, norbornene-2-carboxylic ethyl ester 1b reacted with 2p to give 6-exo-R_F-5-endo-iodo adduct 3bp and 5-exo-R_F-6-endo-iodo adduct 5bp in the ratio of 4:1. While 1c, which has a heavy crowded group in the 2-endo-position, gave 6-exo-R_F-5-endo-iodo adduct 3cp and polyfluoroalkylated product 4cp retaining the trans-configuration and the exo-orientation of R_F group. The fluoroalkylation-lactonization reaction occurred in the reaction of norbornene-2-endo-carboxylic acids 1d and 1e with polyfluoroalkyl iodides to afford the corresponding fluoroalkylated γ-lactone products (7dp-7ds, and 7em-7er). The configuration of the products was further confirmed by 2D NMR and X-ray diffraction analyses for the first time.

Full text of DOI:10.1016/j.tet.2006.08.042

Tetrahedron 62 (2006) 10091–10099
Sodium dithionite initiated regio- and stereoselective radical
addition of polyfluoroalkyl iodide with norbornene analogs
a
a
a
a
Fanhong Wu,a,b, Fanhua Xiao, Xianjin Yang, Yongjia Shen and Tieying Pan
*
aCollege of Chemistry and Pharmaceutics, East China University of Science and Technology, Shanghai 200237, China
bKey Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
Received 8 June 2006; revised 8 August 2006; accepted 11 August 2006
Available online 1 September 2006
Abstract—Sodium dithionite initiated free-radical addition of polyfluoroalkyl iodides (2m–2s) with norbornene 1a and its derivatives, such
as norbornene-2-carboxylates 1b and 1c, and norbornene-2-carboxylic acids 1d and 1e was investigated. In all the cases, the addition of RF
group was stereoselectively delivered at exo-position and the predominant configuration of products was trans. Under the similar condition,
norbornene-2-carboxylic ethyl ester 1b reacted with 2p to give 6-exo-RF-5-endo-iodo adduct 3bp and 5-exo-RF-6-endo-iodo adduct 5bp in the
ratio of 4:1. While 1c, which has a heavy crowded group in the 2-endo-position, gave 6-exo-RF-5-endo-iodo adduct 3cp and polyfluoro-
alkylated product 4cp retaining the trans-configuration and the exo-orientation of RF group. The fluoroalkylation–lactonization reaction
occurred in the reaction of norbornene-2-endo-carboxylic acids 1d and 1e with polyfluoroalkyl iodides to afford the corresponding fluoro-
alkylated g-lactone products (7dp–7ds, and 7em–7er). The configuration of the products was further confirmed by 2D NMR and X-ray
diffraction analyses for the first time.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
asymmetrical substrates under mild reaction conditions.
Herein we investigated the regio- and stereoselectivity of
the radical anion addition of polyfluoroalkyl iodides with
norbornene and some asymmetrical derivatives initiated by
sodium dithionite.
The free-radical addition reaction of polyfluoroalkyl iodides
with unsaturated compounds, such as olefins and alkynes,
was an important method to prepare fluorinated compounds,
which could usually be initiated by high temperature, UV,
peroxide, metals, metal complexes, etc.1 The reactions initi-
ated by the sulfinatodehalogenated reagents, such as sodium
dithionite, sodium disulfite, Rongalite, thiourea dioxide, and
so on, have been extensively studied in our laboratory.2 This
reaction and its applications in industry have been described
in many literatures,3 however, the stereochemistry of this
addition reaction, which played important roles in its theo-
retical chemistry and industrial utility, had seldom been
mentioned. Accordingly, we had paid much attention to it
and hoped to do some research in this aspect. Norbornene
and its derivatives were usually chosen for the investigation
of stereoselective addition of electrophiles at the double
bond due to its special spatial structure,4 however, the addi-
tion of norbornene analogs with polyfluoroalkyl iodides
was examined in few cases in the literature. Brace investi-
gated the reaction of norbornene and its symmetrical 2,3-
dicarboxylic acid derivatives with polyfluoroalkyl iodides
and pointed out that the configuration of the adducts was
determined by the steric and electronic factor of the sub-
strates and the reaction conditions,5 therefore the high
stereoselective addition might be reasonable by using the
2. Results and discussion
2.1. The reaction of norbornene 1a with polyfluoroalkyl
iodide
The reaction of norbornene 1a with polyfluoroalkyl iodides
was investigated at first. In the presence of sodium dithionite
and sodium bicarbonate, the free-radical addition of RFI
(2m–2q) to norbornene 1a occurred smoothly at room tem-
perature in aqueous acetonitrile solution (CH3CN–H2O¼3:1
(v/v)), after usual workup only trans-adduct with RF at the
exo-position (3am–3aq) was isolated in 63–91% yields by
column chromatography (Scheme 1 and Table 1), which
were consistent with the results reported by Brace.5a,b The
heavy steric hindrance of RF led to its attacking at the double
bond from the exo-position of 1a followed by the endo-
oriented attack of iodine. By changing RFI to uncrowded
ethyl iododifluoroacetate (2r) the mixture of trans-adduct
(3ar) and cis-adducts (4ar) was obtained in 87% overall
yield in the ratio of 5:1 (Scheme 2). We had reported that
the addition of 2r with cyclopentene and cyclohexene gave
only trans-adduct for the former and cis–trans mixture
* Corresponding author. E-mail: wfh@ecust.edu.cn
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.08.042

10092
F. Wu et al. / Tetrahedron 62 (2006) 10091–10099
NOE
RF
H7s
H7a
7
Na2S2O4/NaHCO3
RFI
+
H4
H2x
I
H6x
6
2
I
1
H6n
4
3am~3aq
2m~2q
H5x
C4F8Cl
1a
3
H4
5
H5n
H3n
RF = Cl(CF2)n n=2, m; n=4, p; n=8, q
F(CF2)n n=3, n; n=6; s
(CF3)2CF o
Figure 1.
CF2CO2E r
demonstrated its trans-configuration with RF at exo-position
and iodine atom at endo-position.
Scheme 1.
2.2. The reaction of 5-norbornene-2-endo-carboxylic
acid ester 1b and 1c with RFI
Table 1. Addition of norbornene with RFI
Entry Substrates RFI Products
Configuration
Yields
(%)
When 1b reacted with 2p under the same condition, two
adducts 3bp and 5bp were obtained in the ratio of 4:1
(Table 2). Spectral data (1D and 2D NMR) showed that RF
was at the exo-position of C5 and iodine was at the endo-
position of C6 of norbornene in 3bp whereas RF was at
the exo-position of C5 and iodine was at the endo-position
of C6 in 5bp (Scheme 3).
RF
RF/I
1
2
3
4
5
6
1a
1a
1a
1a
1a
1a
2m 3am
exo trans
exo trans
exo trans
exo trans
exo trans
78
82
87
87
91
2n
2o
2p
2q
2r
3an
3ao
3ap
3aq
3ar–4ar (5:1) exo trans+cis 87
Table 2. Addition of norbornene-2-endo-carboxylic ester with RFI
(1:1.6) for the latter under the similar condition.6 It has been
reported that different ratio of trans- and cis-adducts was ob-
tained in the radical addition of ethyl bromoacetate with nor-
bornene bearing various steric substituents.5a,7 Therefore it
can be speculated that the mode of addition depends heavily
on the adding group and the structure of substrates in this
reaction.
Entry Substrates RFI Products
Configuration Overall
yields (%)
RF RF/I
2p 3bp–5bp (4:1) exo trans
1
2
1b
1c
63
2p 6cp–5cp (1:3) exo trans (5cp) 88
RF
I
I
+
:
+
RF
RF
I
RF
RFI
Na2S2O4/NaHCO3
+
:
+
CO2Et
CO2Et
RFI
CO2Et
1b
2p
3bp
5bp
I
1a
2r
3ar
4ar
R
F = p: Cl(CF2)4
4
1
RF = r: CF2CO2Et
Scheme 2.
5
1
Scheme 3.
In order to examine steric hindrance effect, norbornene-
2-endo-ester 1c, bicyclo[2.2.1]hept-5-ene-2-carboxylic acid-
4,4-dimethyl-2-oxo-tetrahydro-furan-3-yl ester, was allowed
to react with 2p (Scheme 4). Ester 1c was synthesized via
Diels–Alder addition of cyclopenta-1,3-diene with acrylic
acid 4,4-dimethyl-2-oxotetrahydro-furan-3-yl ester, which
was condensed from 3-hydroxy-4,4-dimethyl-dihydro-furan-
2-one and acryl chloride.10 The reaction of 1c with 2p
proceeded at room temperature in the water and acetonitrile
solution (v/v¼1:1), two products (5cp–6cp¼3:1) were
isolated by column chromatography (eluent: PE–EA¼30:1)
in 88% overall yield (Table 2).
The IR and 1H NMR spectra were usually utilized to deter-
mine the configuration of adducts in the literatures,5a,b
herein the stereo configuration of adducts was determined
via 2D NMR spectrum. Compound 3ap (Fig. 1) was taken
as a typical example for the configuration analyses of com-
pounds 3. The assignment of the chemical shift in 1H NMR
1
was accomplished by the analysis of H NMR, 13C NMR,
DEPT, HMBC, HMQC, etc. The observation of strong cor-
relativity of H1–H2 and no obvious correlativity of H3–H4
in 1H–1H COSY combined with interaction of H2–H7s
and no or weak interaction of H3–H7s in NOESY
RF
I
+
:
+
RFI
RF
CO2R
CO2R
CO2R
1c
2p
6cp
5cp
1
3
RF = p: Cl(CF2)4;
R =
O
O
Scheme 4.

F. Wu et al. / Tetrahedron 62 (2006) 10091–10099
10093
Similar analyses of the spectral data (1D and 2D NMR)
showed that 5cp was a trans-adduct with RF at the exo-
position of C5 and iodine at the endo-position of C6 of
norbornene, and 6cp was the fluoroalkylated–deiodined
product with RF at the exo-position of C6 of norbornene,
which was formed via the addition of H atom (from the
solvent) to the C5 after the addition of RF to exo-position
of norbornene. To ascertain our deduction, the structure
was further confirmed by the X-ray crystallography of 5cp
and 6cp (Figs. 2 and 3).
It was observed from the crystallography of 6cp that the
6-endo-position of norbornene had been filled with the
crowded group (acrylic acid 40,40-dimethyl-20-oxo-tetra-
hydro-furan-30-yl ester) at 2-endo-position of norbornene,
and the exo-position of the norbornene was crowded with
great group C4F8Cl in the neighboring C3 and the 7-CH2
group, which make it hard for the bulky iodine atom to
approachtheC6fromtheendoortheexo-positionofnorborn-
ene, however, the media H2O molecule, which surrounded
the free-radical intermediate could attack the C6 of norborn-
ene to give compound 6cp.
2.3. The reaction of norbornene-carboxylic acid 1d and
2-methyl-norbornene-carboxylic acid 1e with RF
Besides the 6-exo-fluoroalkyl-5-endo-iodo adducts 5dp–5ds
and the fluoroalkylated compounds 6dp–6ds, the addition of
norbornene-2-endo-carboxylic acid 1d with polyfluoroalkyl
iodide gave the corresponding lactones 7dp–7ds (Scheme 5
and Table 3). Similarly in all the cases RF was added at
exo-position of norbornene and iodine atom was added at
endo-position. The lactone was produced via the iodolacto-
nization of the intermediate adduct 5-exo-fluoroalkyl-
6-endo-iodo-bicyclo[2.2.1]heptane-2-endo-carboxylic acid
under the basic condition. The double peak at dH¼4.95 ppm
1
in H NMR, the peak at dC¼78.7 ppm in 13C NMR, and
n¼1780 cmꢀ1 in IR revealed that there existed the latcone
group in 7dp–7ds. All the same configurations were con-
firmed by the analysis of COSY and NOESY spectra for
7dp–7ds, 6dp–6ds, and 5dp–5ds and further by the crystal-
lography of 5ds (Fig. 4).
It is curious that there were no polyfluoroalkylated products
formed except the 5-exo-RF-latcone 7em–7ep and the 6-exo-
RF-5-endo-adduct 5em–5ep observed in the reaction of RFI
with 1e, which have much similar structure with 1d (Table 3
and Scheme 6). The ratio of 5em–5ep and 7em–7ep was
from 2.1:1.0 to 0.9:1.0 with 50–72% overall yields. The
crystallography of 5eo (Fig. 5) and 2D NMR spectra were
consistent with the trans-configuration of 5em–5ep and
7em–7ep with RF at the exo-position of norbornene.
Figure 2. ORTEP of compound 5cp.
Table 3. Addition of norbornene-2-endo-carboxylic acid with RFI
Entry Substrate RFI Product
Configuration Yield
(%)
RF RF/I
1
2
3
4
5
6
1d
1d
1d
1e
1e
1e
2p 5dp–6dp–7dp (1.0:1.1:0.8) exo trans (5dp) 70
2q 5dq–6dq–7dq (1.0:1.5:0.3) exo trans (5dq) 52
2s 5ds–6ds–7ds (1.0:1.1:0.8) exo trans (5ds) 58
2n 5en–7en (1.0:1.0)
2o 5eo–7eo (2.1:1.0)
2p 5ep–7ep (0.9:1.0)
exo trans (5en) 67
exo trans (5eo) 50
exo trans (5ep) 72
Figure 3. ORTEP of compound 6cp.
RF
RF
I
RF
RFI
+
+
+
COOH
O
COOH
6dp, 6dq, 6ds
COOH
O
2p, 2q, 2s
5dp, 5dq, 5ds
7dp, 7dq, 7ds
1d
RF = p: Cl(CF2)4; q: Cl(CF2)8; s: F(CF2)6
Scheme 5.

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F. Wu et al. / Tetrahedron 62 (2006) 10091–10099
2.4. Mechanism for the free-radical addition of norborn-
ene and its 2-substituted derivatives with RFI initiated
by Na2S2O4
According to the literatures,3c,5 the supposed mechanism
ꢁ
was described as following (Scheme 7): (1) RF was
generated from RFI under the initiation of Na2S2O4, (2)
5-exo-RF intermediates A1 and 6-exo-RF intermediate A2
were produced by stereoselectively exo-oriented addition
ꢁ
of RF to C]C of the norbornene and its derivatives, and
(3) 5-exo-RF-6-endo-iodo adduct B1 was produced from
the reaction of A1 with RFI and 6-exo-RF-5-endo-iodo
adduct B2 was produced from the reaction of A1 with RFI.
In this mechanism, the third step was the rate-determined
step, which was influenced by steric and electronic effect
of the substrate and adding group and played important roles
in the configuration of the adducts. For the uncrowded RFI
(e.g., ICF2COOEt), some cis-adducts were produced accom-
panying the trans-adducts and when the 2-endo-position
was taken by bulky group, an anion C1 was obtained by
transferring an electron to radical A1 from S2O24ꢀ, and
then the hydrogenated product B3 was obtained by the
abstraction of proton from H2O (Scheme 8). For norborn-
ene-2-carboxylic acids 1d and 1e, the lactone E was
obtained by base-catalyzed iodolactonization from the
adduct D1 (Scheme 8).
Figure 4. ORTEP of 5ds.
RF
Me
Me
RFI
I
+
+
Me
RF
O
COOH
COOH
O
5en, 5eo, 5ep
2n, 2o, 2p
7en, 7eo, 7ep
1e
RF = n: F(CF2)3; o: (CF3)2CF; p: Cl(CF2)4
Scheme 6.
RF
R1
R2
B1
(major)
I
RF
RF
(appear when
RF is small)
RFI
I
R1
R2
B2
R1
.
H2O
R2
A1
RF
(appear when
R
2 is bulky)
R1
R2
B3
RF.
R1
R2
I
.
RF
RFI
R1
R2
B4
(minor)
RF
R1
R2
A2
Scheme 7. Mechanism proposed for this reaction.
Figure 5. ORTEP of 5eo.
RF
RF
-
RF
2-
S2O4
RF.
H2O
R1
R2
R1
R2
B3
R1
R2
C1
R1
R2
.
A1
RF
RF
RF
OH-
RF.
RFI
R1
COOH
R1
COOH
D1
R1
COOH
B1
.
I
O
O
E
Scheme 8. Mechanism proposed for the production of hydrogenated product and lactonizated product.

F. Wu et al. / Tetrahedron 62 (2006) 10091–10099
10095
Generally we concluded that the free-radical addition reac-
tion of norbornene and its 2-substituted derivatives with
RFI initiated by sodium dithionite was of high regio- and
stereoselectivity with the addition of the RF group to exo-
position due to the narrow space of the endo-position of nor-
bornene and its 2-endo-derivatives. The main products were
of trans-configuration due to the heavily steric hindrance of
the neighboring RF group, which led to the predominant ad-
dition of iodine at the endo-position, and in some cases, the
polyfluoroalkylated products were produced in concomitant
with adducts. In the case of norbornene-2-endo-carboxylic
acids, polyfluoroalkylated lactones were obtained from the
polyfluoroalkylation–lactonization reaction of the adduct
5-exo-RF-6-endo-iodobicyclo[2.2.1]heptane-2-endo-carb-
oxylic acid under the basic condition.
C-3), 115.5–118.0 (m, CF2), 119.0–124.7 (m, CF2Cl);
HRMS calcd for C9H10ClF4I: 355.9452, found: 355.9464.
3.2.2. 3-exo-(Heptfluoro-propyl)-2-endo-iodobicyclo-
[2.2.1]heptane (3an). Oil. IR (film): nmax 2980 (C–H),
1340, 1230 (C–F), 1180, 1110, 930, 740, 650 (C–I) cmꢀ1
;
1H NMR (500 MHz, CDCl3): d 1.24–1.26 (2H, m, H-7, H-
5), 1.56–1.60 (1H, m, H-6), 1.61–1.75 (2H, m, H-5, H-7),
1.80–1.90 (1H, m, H-6), 2.20–2.28 (1H, m, H-3), 2.36
(1H, s, H-4), 2.42 (1H, s, H-1), 4.20–4.26 (1H, m, H-2);
19F NMR (470.5 MHz, CDCl3): dꢀ126.1 (2F, s, CF2CF3),
ꢀ119.1 (2F, dd, J¼1411.5, 277.8 Hz, CHCF2), ꢀ81.5 (3F,
t, J¼10.4 Hz, CF3); 13C NMR (125.7 MHz, CDCl3):
d 24.8 (s, C-2), 26.4 (s, C-6), 28.7 (s, C-5), 34.0 (s, C-7),
36.8 (s, C-4), 43.6 (s, C-1), 54.5 (t, J¼20.1 Hz, C-3),
106.0–120.5 (m, CF2CF2CF3); HRMS calcd for
C10H10F7I: 389.9716, found: 389.9720.
3. Experimental
3.1. General
3.2.3. 3-exo-(Heptfluoroisopropyl)-2-endo-iodo-bicyclo-
[2.2.1]heptane (3ao). Oil. IR (film): nmax 2980 (C–H),
1300, 1220 (C–F), 1150, 1030, 970, 740, 650 (C–I) cmꢀ1
;
Melting points were measured in WRS-1B digital melting
point instrument. IR spectra were taken on a Nicolet FTIR
20sx IR spectrophotometer. 1H NMR spectra were measured
on a Bruker AC500 (500 MHz) spectrometer using TMS as
internal standard. 19F NMR spectra were taken on a Bruker
AC500 (500 MHz) spectrometer; chemical shifts are re-
ported as dCFCl ðdCFCl ¼ dTFA ꢀ 76:8Þ, negative for upfield
1H NMR (500 MHz, CDCl3): d 1.25–1.40 (2H, m, H-5,
H-7), 1.62–1.75 (3H, m, H-5, H-6, H-7), 1.80–2.00 (1H, m,
H-6), 2.25–2.31 (1H, m, H-3), 2.41 (1H, s, H-4), 2.43 (1H,
s, H-1), 4.30–4.50 (1H, m, H-2), 19F NMR (470.5 MHz,
CDCl3): d ꢀ75.8 (6F, d, J¼682.2 Hz, (CF3)2), ꢀ76.4 (1F,
m, CF); 13C NMR (125.7 MHz, CDCl3): d 28.5 (s, C-2),
28.7 (s, C-6), 31.3 (s, C-5), 35.3 (s, C-7), 39.1 (s, C-4),
46.1 (s, C-1), 55.6 (d, J¼18.9 HZ, C-3), 92.1 (dm,
J¼206.1, 30.8 Hz, CF), 121.7 (ddd, J¼576.0, 288.0,
28.9 Hz, (CF3)2); HRMS calcd for C10H10F7I: 389.9716,
found: 389.9717.
3
3
shifts. Mass spectra were obtained on a Finnigan GC–MS
4021 spectrometer. X-ray data were measured at 293 K
on a Bruker SMART CCD diffractomer with graphite
monochromated Mok\a radiation. Column chromatography
was performed using silica gel H, particle size was
10–40 mm.
3.2.4. 3-exo-(4-Chloro-1,1,2,2,3,3,4,4-octafluorobutyl)-
2-endo-iodo-bicyclo[2.2.1]heptane (3ap). Oil. IR (film):
nmax 2980 (C–H), 1230 (C–F), 1080, 760, 720, 640 (C–I)
3.2. Typical experimental procedure for the reaction of
the norbornene 1a with RFI
1
cmꢀ1; H NMR (500 MHz, CDCl3): d 1.20–1.40 (2H, m,
H-5, H-7), 1.50–1.68 (1H, m, H-6), 1.80–1.92 (2H, m,
H-5, H-7), 2.35–2.40 (1H, m, H-3), 2.44 (1H, s, H-4),
2.49 (1H, s, H-1), 4.31–4.35 (1H, m, H-2); 19F NMR
(470.5 MHz, CDCl3): d ꢀ120.9 (4F, m, CF2CF2), ꢀ118.8
(2F, m CHCF2), ꢀ68.8 (2F, m, CF2Cl); 13C NMR
(125.7 MHz, CDCl3): d 26.7 (s, C-2), 28.2 (s, C-6), 30.4
(s, C-5), 35.7 (s, C-7), 38.6 (s, C-4), 45.3 (s, C-1), 56.4 (t,
J¼20.1 Hz, C-3), 110.0–125.2 (m, (CF2)4); HRMS calcd
for C11H10ClF8I: 455.9388, found: 455.9407.
Norbornene (10 mmol) and polyfluoroalkyl iodide
(12 mmol) were dissolved in the solution of water (10 mL)
and acetonitrile (10 mL). Sodium dithionite (3.7 g) and
sodium bicarbonate (1.85 g) were added to the solution.
The mixture was stirred at ambient temperature for 6 h.
When the reaction was accomplished, the mixture was
treated with water (ca. 50 mL). The mixture was extracted
with ether of 3ꢂ20 mL. The combined organic layers were
washed with saturated brine and dried over anhydrous
sodium sulfate. After the evaporation of ether, the crude
product was purified by column chromatography (PE–
EA¼200:1) to give products 3am–3ar and 4ar.
3.2.5. 3-exo-(8-Chloro-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-hexa-
decafluorooctyl)-2-endo-iodo-bicyclo[2.2.1]heptane
(3aq). White solid. Mp: 56–57 ꢃC; IR (film): nmax 2980 (C–
1
H), 1220 (C–F), 1150, 840, 770, 670, 650 (C–I) cmꢀ1; H
3.2.1. 3-exo-(2-Chloro-1,1,2,2-tetrafluoroethyl)-2-endo-
iodobicyclo[2.2.1]heptane (3am). Oil. IR (film): nmax
2980 (C–H), 1230 (C–F), 1150, 1080, 930, 800, 750, 640
NMR (500 MHz, CDCl3): d 1.31–1.33 (2H, m, H-7, H-5),
1.60–1.65 (1H, m, H-6), 1.68–1.72 (2H, m, H-5, H-7),
1.80–1.90 (1H, m, H-6), 2.35–2.38 (1H, m, H-3), 2.44
(1H, s, H-4), 2.49 (1H, s, H-1), 4.30–4.33 (1H, m, H-2);
19F NMR (470.5 MHz, CDCl3): d ꢀ122.7 (6F, m, 3ꢂCF2),
ꢀ122.2 (2F, m, CF2), ꢀ121.8 (2F, m, CF2), ꢀ121.1 (2F,
m, CF2), ꢀ118.2 (2F, dd, J¼1270.4, 282.3 Hz, CHCF2),
ꢀ69.0 (2F, m, CF2Cl); 13C NMR (125.7 MHz, CDCl3):
d 26.0 (s, C-2), 27.5 (s, C-6), 29.7 (s, C-5), 35.0 (s, C-7),
37.9 (s, C-4), 44.6 (s, C-1), 57.7 (t, J¼20.1 Hz, C-3),
108.7–124.2 (m, (CF2)8); HRMS calcd for C15H10ClF16
(MꢀI): 529.0216, found: 529.0222.
(C–I) cmꢀ1 1H NMR (500 MHz, CDCl3): d 1.24–1.26
;
(2H, m, H-7, H-5), 1.56–1.58 (2H, m, H-6, H-5), 1.62–
1.67 (1H, m, H-7), 1.82–1.90 (1H, m, H-6), 2.20–2.32 (1H,
m, H-3), 2.38 (1H, s, H-4), 2.42 (1H, s, H-1), 4.15–4.25
(1H, m, H-2); 19F NMR (470.5 MHz, CDCl3): d ꢀ117.1
(2F, dd, J¼385.8, 268.2 Hz, CF2CF2Cl), ꢀ69.3 (2F, dd,
J¼240.0, 174.1 Hz, CF2Cl); 13C NMR (125.7 MHz,
CDCl3): d 27.3 (s, C-2), 28.2 (s, C-6), 30.4 (s, C-5), 35.6
(s, C-7), 38.8 (s, C-4), 45.4 (s, C-1), 56.0 (t, J¼20 Hz,

10096
F. Wu et al. / Tetrahedron 62 (2006) 10091–10099
3.2.6. 3-exo-Difluoro-(2-endo-iodo-bicyclo[2.2.1]hept-3-
yl)-acetic acid ethyl ester (3ar). Oil. IR (film): nmax 2980,
(4F, m, 2ꢂCF2), ꢀ119.1 (2F, dd, J¼2583, 282.3 Hz, CF2),
ꢀ68.8 (2F, m, CF2); 13C NMR (125.8 MHz, CDCl3): d 14.6
(s, CH3), 16.3 (s, C-6), 32.2 (s, C-3), 39.5 (s, C-7), 39.6 (s,
C-4), 46.0 (s, C-2), 47.7 (s, C-1), 55.2 (t, C-5), 61.7 (s,
C–O), 109.6–125.1 (m, (CF2)4), 173.2 (s, C]O); HRMS
calcd for C14H14F8ClO2I: 527.9599, found: 527.9594.
2900, 1770 (s, ester), 1450, 1310, 1080, 850, 780 cmꢀ1
;
1H NMR (500 MHz, CDCl3): d 1.25–1.31 (1H, m, H-7,
H-5), 1.38 (3H, t, J¼7.1 Hz, CH3), 1.60–1.62 (1H, m,
H-6), 1.63–1.65 (1H, m, H-5), 1.68–1.70 (1H, m, H-7),
1.75–1.85 (1H, m, H-5), 2.20–2.30 (1H, m, H-2), 2.35
(1H, s, H-1), 2.47 (1H, s, H-4), 4.20–4.40 (1H, m, H-3),
4.37 (2H, q, J¼7.1 Hz, OCH2); 19F NMR (470.5 MHz,
CDCl3): d ꢀ116.2 (dd, JF,F¼253.8 Hz, JF,H¼18.8 Hz, 1F),
ꢀ110.1 (dd, JF,F¼253.8 Hz, JF,H¼14.1 Hz, 1F); 13C NMR
(125.8 MHz, CDCl3): d 14.6 (s, CH3), 27.9 (s, C-6), 27.9
(s, C-2), 30.6 (s, C-5), 35.6 (s, C-7), 38.0 (s, C-4), 45.6 (s,
C-1), 58.3 (t, C-3), 63.9 (s, OCH2), 116.2 (t, CF2), 164.3
(t, C]O); HRMS calcd for C11H15 F2IO2: 344.0085, found:
344.0080.
3.3.4. 6-exo-(4-Chloro-1,1,2,2,3,3,4,4-octafluorobutyl)-5-
endo-iodo-bicyclo[2.2.1]heptane-2-endo-carboxylic acid
ethyl ester (5bp). Oil. IR (film): nmax 2980, 1730, 1200,
1
1100, 740, 680 cmꢀ1; H NMR (500 MHz, CDCl3): d 1.26
(3H, t, J¼7.1 Hz, CH3), 1.45 (1H, d, J¼10.9 Hz, H-7a),
1.82 (1H, d, J¼10.9 Hz, H-7s), 1.90–1.95 (1H, m, H-3x),
2.29 (1H, ddd, J¼13.6, 5.8, 2.6 Hz, H-3n), 2.54 (1H, br s
H-4), 2.65–2.68 (1H, m, H-6), 2.74 (1H, br s H-1), 2.80–
2.84 (1H, m, H-2), 4.15–4.20 (2H, m, CH2O), 4.32–4.34
(1H, m, H-5); 19F NMR (470.5 MHz, CDCl3): d ꢀ120.9
(2F, m, CF2), ꢀ120.8 (2F, dd, J¼376.4, 282.3 Hz, CF2),
ꢀ118.1 (2F, dd, J¼1882, 282.3 Hz, CF2), ꢀ68.8 (2F, m,
CF2); 13C NMR (125.8 MHz, CDCl3): d 14.7 (s, CH3),
25.2 (s, C-5), 30.5 (s, C-3), 37.8 (s, C-7), 42.2 (s, C-1),
45.8 (s, C-4), 46.5 (s, C-2), 51.4 (t, C-6), 61.6 (s, C–O),
109.9–125.4 (m, (CF2)4), 173.3 (s, C]O); HRMS calcd
for C14H14F8ClO2I: 527.9599, found: 527.9605.
3.3. Typical experimental procedure for the reaction of
the norbornene (1b and 1c) with RFI
Norbornene derivative 1b or 1c (10 mmol) and polyfluoro-
alkyl iodide 2p (12 mmol) were dissolved in the solution
of water (10 mL) and acetonitrile (10 mL). Sodium dithion-
ite (3.7 g) and sodium bicarbonate (1.85 g) were added to the
solution. The mixture was stirred at ambient temperature for
6 h. When the reaction was accomplished, the mixture was
treated with water (ca. 50 mL). The mixture was extracted
with ether of 3ꢂ20 mL. The combined organic layer was
washed with saturated brine and dried over anhydrous
sodium sulfate. After the evaporation of ether, the crude
product was purified by column chromatography (PE–
EA¼40:1 for 1b and 30:1 for 1c) to give products 3bp and
5bp for 1b or 5cp and 6cp for 1c.
3.3.5. 6-exo-(4-Chloro-1,1,2,2,3,3,4,4-octafluorobutyl)-5-
endo-iodo-bicyclo[2.2.1]heptane-2-endo-carboxylic acid-
40,40-dimethyl-20-oxo-tetrahydrofuran-30-yl ester (5cp).
White solid. Mp: 98.1–98.4 ꢃC; IR (KBr): nmax 2990, 1800
(g-lactone), 1750, 1380, 1240 (C–F), 1180, 1120, 1080,
1
840, 740, 650, 560 cmꢀ1; H NMR (500 MHz, CDCl3):
d 1.11 (3H, s, CH3, H-60s), 1.15 (3H, s, CH3, H-6a), 1.51
(1H, d, J¼10.9 Hz, H-7a), 1.89 (1H, d, J¼11.0 Hz, H-7s),
2.00–2.12 (1H, m, H-3x), 2.35–2.40 (1H, m, H-3n), 2.58
(1H, s, H-4), 2.70–2.77 (1H, m, H-6), 2.80 (2H, s, H-1),
3.00–3.10 (1H, m, H-2), 4.03 (1H, d, J¼9.0 Hz, H-50s),
4.06 (1H, d, J¼9.0 Hz, H-50a), 4.32–4.35 (1H, m, H-5),
5.42 (1H, s, H-30); 19F NMR (470.5 MHz, CDCl3):
d ꢀ120.8 (2F, m, CF2), ꢀ120.3 (2F, m, CF2), ꢀ117.5 (2F,
m, CF2), ꢀ68.9 (2F, m, ClCF2); 13C NMR (125.8 MHz,
CDCl3): d 20.4 (s, C-60s), 23.2 (s, C-60a), 24.9 (s, C-5),
30.8 (s, C-3), 38.1 (s, C-7), 40.7 (s, C-40), 42.4 (s, C-1),
45.9 (s, C-4), 46.3 (s, C-2), 50.1 (t, C-6), 76.3 (s, C-30),
76.9 (s, C-50), 108.3–123.0 (m, (CF2)4), 172.4 (s, C-8),
172.6 (s, C-20), HRMS calcd for C18H18ClF8O4 (MꢀI):
485.0766, found: 485.0765.
3.3.1. Bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid
ethyl ester (1b).8,9 1H NMR (500 MHz, CDCl3): d 1.23
(3H, t, J¼7.1 Hz, CH3), 1.20–1.26 (1H, m, H-7), 1.40–
1.45 (2H, m, H-7, H-2), 1.88–1.92 (1H, m, H-3), 2.90 (1H,
s, H-4), 2.90–2.95 (1H, m, H-2), 3.21 (1H, s, H-1), 4.09
(2H, q, J¼7.1 Hz, CH3CH2), 5.93 (1H, q, J¼3 Hz, H-5),
6.19 (1H, q, J¼3.0 Hz, H-6).
3.3.2. Bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid-
4,4-dimethyl-2-oxotetrahydrofuran-3-yl ester (1c).10
White solid. Mp: 116.5–117 ꢃC. 1H NMR (500 MHz,
CDCl3): d 1.15 (3H, s, CH3-a), 1.18 (3H, s, CH3-b), 1.33
(1H, d, J¼8.2 Hz, H-7), 1.47 (1H, s, H-7), 1.49 (1H, m,
H-3), 1.95 (1H, m, H-3), 2.96 (1H, s, H-4), 3.16 (1H, m,
H-2), 3.27 (1H, m, H-1), 4.04 (2H, dd, J¼20.7, 9.0 Hz,
H-50), 5.33 (1H, s, H-30), 5.91 (1H, dd, J¼5.6, 2.8 Hz,
H-5), 6.26 (1H, dd, J¼5.6, 3.1 Hz, H-6).
3.3.6. 5-exo-(4-Chloro-1,1,2,2,3,3,4,4-octafluorobutyl)-
bicyclo[2.2.1]heptane-2-endo-carboxylic acid-4,4-
dimethyl-2-oxo-tetrahydrofuran-3-yl ester (6cp). White
solid. Mp: 143.6–144.6 ꢃC; IR (KBr): nmax 2980, 1780 (g-
lactone), 1760, 1460, 1380, 1200 (C–F), 1150, 1100, 990,
1
3.3.3. 5-exo-(4-Chloro-1,1,2,2,3,3,4,4-octafluorobutyl)-6-
endo-iodo-bicyclo[2.2.1]heptane-2-endo-carboxylic acid
ethyl ester (3bp). White solid. Mp: 39–41 ꢃC; IR (film):
720, 700 cmꢀ1; H NMR (500 MHz, CDCl3): d 1.12 (3H,
s, CH3), 1.22 (3H, s, CH3), 1.44 (1H, d, J¼10.3 Hz, H-7a),
1.60–1.65 (1H, m, H-6), 1.69 (1H, d, J¼10.3 Hz, H-7s),
1.75–1.79 (2H, m, H-6, H-3n), 1.81 (1H, td, J¼11.4,
4.2 Hz, H-3x), 2.35–2.38 (1H, m, H-5), 2.70 (2H, s, H-1,
H-4), 3.04–3.10 (1H, m, H-2), 4.05 (1H, d, J¼9.1 Hz,
H-50), 4.08 (1H, d, J¼9.1 Hz, H-50), 5.42 (1H, s, H-30);
19F NMR (470.5 MHz, CDCl3): d ꢀ121.5 (4F, m, 2ꢂCF2),
ꢀ117.1 (2F, dd, J¼1091.8, 272.9 Hz, CF2), ꢀ68.8 (2F, m,
ClCF2); 13C NMR (125.8 MHz, CDCl3): d 20.7 (s, CH3,
C-60s), 23.8 (S, CH3, C-60a), 27.9 (s, C-6), 33.6 (s, C-3),
1
nmax 2980, 1720, 1200, 1140, 720, 680 cmꢀ1; H NMR
(500 MHz, CDCl3): d 1.33 (3H, t, J¼7.2 Hz, CH3), 1.39
(1H, d, J¼10.8 Hz, H-7a), 1.75 (1H, d, J¼10.8 Hz, H-7s),
1.90–1.95 (1H, m, H-3x), 2.01 (1H, ddd, J¼13.2, 5.6,
2.6 Hz, H-3n), 2.60 (1H, br s, H-4), 2.63–2.65 (1H, m,
H-5), 2.97–3.00 (1H, m, H-2), 3.04 (1H, br s H-1), 4.10–
4.20 (1H, m, CH2O), 4.10–4.20 (1H, m, H-6), 4.25–4.28
(1H, m, CH2O); 19F NMR (470.5 MHz, CDCl3): d ꢀ121.9

F. Wu et al. / Tetrahedron 62 (2006) 10091–10099
10097
38.2 (s, C-4), 39.4 (s, C-7), 40.6 (s, C-1), 40.9 (s, C-40), 43.4
(t, C-5), 45.2 (s, C-2), 75.7 (s, C-30), 76.8 (s, C-50), 109.7–
125.2 (m, (CF2)4), 172.9 (s, C-8), 173.9 (s, C-20).
d ꢀ73.7 (3F, m, CF3), ꢀ72.4 (3F, m, CF3); 13C NMR
(125.8 MHz, CDCl3): d 25.8 (s, C-5), 27.2 (s, C-9), 34.0
(s, C-7), 39.4 (s, C-3), 46.7 (s, C-4), 47.9 (s, C-1), 51.7 (d,
J¼19 Hz, C-6), 51.8 (s, C-2), 91.7–94.2 (m, CF), 120.3–
122.9 (m, 2ꢂCF3), 181.3 (s, C]O); HRMS calcd for
C12H12F7IO2: 447.9770, found: 447.9815.
3.4. The addition of norbornene-2-endo-carboxylic acid
(1d and 1e) with RFI
Compound 1d or 1e (5 mmol) was dissolved in 2 N NaOH
aqueous solution (5 mL). Acetonitrile (15 mL), RFI
(6 mmol), sodium dithionite (2.2 g), and sodium bicarbonate
(1.70 g) were then added to the solution. After stirring for 5–
8 h the mixture was treated with water (ca. 50 mL). The mix-
ture was extracted with ether of 3ꢂ20 mL. The combined
organic layer was washed with saturated brine and dried
over anhydrous sodium sulfate. After the evaporation of
ether, the crude product was purified by column chromato-
graphy (PE–EA¼20:1) to give products 7dp–7ds, 5dp–
5ds, and 6dp–6ds for 1d or 5em–5ep and 7em–7ep for 1e.
3.4.4. 6-exo-(4-Chloro-1,1,2,2,3,3,4,4-octafluorobutyl)-5-
endo-iodo-2-exo-methyl-bicyclo[2.2.1]-heptane-2-endo-
carboxylic acid (5ep). White solid. Mp: 173.7–174.1 ꢃC; IR
(KBr): nmax 2500–3500 (OH), 1700, 1300, 1180, 1130, 720,
680 cmꢀ1; 1H NMR (500 MHz, CDCl3): d 1.41 (3H, s, H-8),
1.53 (1H, dq, J¼14, 2 Hz, H-3), 1.74 (2H, s, H-7), 2.47 (1H,
s, H-1), 2.51 (1H, s, H-4), 2.55–2.60 (1H, m, H-6), 2.68 (1H,
dd, J¼14, 2 Hz, H-1), 4.30–4.34 (1H, m, H-5); 19F NMR
(470.5 MHz, CDCl3): d ꢀ120.8 (4F, m, 2ꢂCF2), ꢀ117.7
(2F, dd, J¼1552.7, 282.3 Hz, CF2), ꢀ68.9 (2F, m, ClCF2);
13C NMR (125.8 MHz, CDCl3): d 23.2 (s, C-5), 26.2 (s,
C-8), 36.6 (s, C-7), 38.2 (s, C-3), 45.2 (s, C-4), 46.6 (s,
C-1), 50.6 (s, C-2), 52.1 (t, C-6), 107.4–124.5 (m, 4ꢂCF2),
180.8 (s, C]O); HRMS calcd for C13H12ClF8IO2:
513.9443, found: 513.9445.
3.4.1. 6-exo-Tridecafluorohexyl-5-endo-iodo-bicyclo-
[2.2.1]heptane-2-endo-carboxylic acid (5ds). White solid.
Mp: 83.4–84.0 ꢃC; IR (KBr): nmax 2500–3500, 3000, 1720,
1420, 1240, 1210, 1180, 1150, 1060, 700, 670 cmꢀ1
;
1H NMR (500 MHz, CDCl3): d 1.48 (1H, d, J¼10.9 Hz,
H-7a), 1.84 (1H, d, J¼11.0 Hz, H-7s), 1.98 (1H, tm,
J¼12.4, H-3x), 2.27 (1H, dm, J¼13.7 Hz, H-3n), 2.56
(1H, s, H-4), 2.76 (1H, dt, J¼24.5, 7.4 Hz, H-6), 2.77 (1H,
s, H-1), 2.80–2.92 (1H, m, H-2), 4.30–4.35 (1H, m, H-5);
19F NMR (470.5 MHz, CDCl3): d ꢀ127.2 (2F, m, CF2),
ꢀ123.8 (2F, m, CF2), ꢀ122.8 (2F, m, CF2), ꢀ121.7 (2F,
m, CF2), ꢀ119.9 (1F, d, J¼277.3 Hz, CF), ꢀ116.3 (1F, d,
J¼282.0 Hz, CF), ꢀ81.8 (3F, m, CF3); 13C NMR
(125.8 MHz, CDCl3): d 24.8 (s, C-5), 30.4 (s, C-7), 37.7
(s, C-3), 42.0 (s, C-4), 45.8 (s, C-1), 46.1 (s, C-2), 50.5 (t,
J¼20 Hz, C-6), 109.1–125.4 (m, (CF2)6CF3), 178.6 (s,
C]O, C-8); HRMS calcd for C14H10F13IO2: 583.9518,
found: 583.9512.
3.4.5. 5-exo-(8-Chloro-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-hexa-
decafluorooctyl)-bicyclo-[2.2.1]heptane-2-endo-carbox-
ylic acid (6dq). White solid. Mp: 96.6–96.8 ꢃC; IR (KBr):
nmax 3000–3600 (OH), 2980, 1720, 1450, 1400, 1220,
1
1160, 1110, 740, 560 cmꢀ1; H NMR (500 MHz, CDCl3):
d 1.42 (1H, d, J¼10.0 Hz, H-7a), 1.68 (1H, d, J¼10.8 Hz,
H-7s), 1.73 (3H, m, H-6, H-3n), 1.80 (1H, td, J¼11.6,
4.2 Hz, H-3x), 2.30–2.34 (1H, m, H-5), 2.68 (1H, d,
J¼3.2 Hz, H-4), 2.72 (1H, s, H-1), 2.90 (1H, dt, J¼10.8,
4.4 Hz, H-2), 11.10 (1H, br s OH); 19F NMR (470.5 MHz,
CDCl3): d ꢀ122.8 (6F, s, 3ꢂCF2), ꢀ122.2 (4F, m,
2ꢂCF2), ꢀ121.1 (2F, s, CF2), ꢀ118.2 (1F, d, J¼277.3 Hz,
CF), ꢀ115.7 (1F, d, J¼277.3 Hz, CF),ꢀ69.0 (2F, t,
J¼13.6 Hz, ClCF2); 13C NMR (125.8 MHz, CDCl3):
d 27.9 (s, C-6), 33.5 (s, C-3), 38.3 (s, C-4), 39.5 (s, C-7),
40.5 (s, C-1), 43.4 (t, J¼20 Hz, C-5), 45.1 (s, C-2), 109.7–
122.4 (m, 8ꢂCF2), 180.5 (s, C]O); HRMS calcd for
C16H11ClF16IO2: 574.0192, found: 574.0187.
3.4.2. 6-exo-Heptafluoropropyl-5-endo-iodo-2-exo-methyl-
bicyclo[2.2.1]heptane-2-endo-carboxylic acid (5en).
White solid. Mp: 165–166 ꢃC; IR (KBr): nmax 2500–3500,
1700, 1220, 1100, 740, 680 cmꢀ1 1H NMR (500 MHz,
;
CDCl3): d 1.42 (3H, s, H-9), 1.50–1.55 (1H, m, H-3n),
1.74 (2H, s, H-7), 2.47 (1H, s, H-1), 2.51 (1H, s, H-4),
2.55 (1H, dt, H-6), 2.60–2.72 (1H, m, H-3x), 4.20–4.35
(1H, m, H-5); 19F NMR (470.5 MHz, CDCl3): d ꢀ125.9
(2F, dd, J¼442.3, 291.7 Hz, CF2), ꢀ118.6 (2F, dd,
J¼1757.3, 284.7 Hz, CF2), ꢀ81.4 (3F, t, J¼11.3 Hz, CF3);
13C NMR (125.8 MHz, CDCl3): d 23.6 (s, C-5), 26.9
(s, C-8), 34.3 (s, C-7), 38.8 (s, C-3), 45.8 (s, C-4), 47.3
(s, C-1), 51.4 (s, C-2), 52.5 (t, J¼20 Hz, C-6), 107.9–120.7
(m, CF2CF2CF3), 182.2 (s, C]O); HRMS calcd for
C12H12F7IO2: 447.9770, found: 447.9775.
3.4.6. 5-exo-Tridecafluorohexyl-bicyclo[2.2.1]heptane-
2-endo-carboxylic acid (6ds). Oil. IR (KBr): nmax 2500–
3500 (OH), 2980, 1710, 1420, 1300, 1240, 1200, 1160,
1
1060, 740, 700, 560 cmꢀ1; H NMR (500 MHz, CDCl3):
d 1.42 (1H, d, J¼10.0 Hz, H-7a), 1.68 (1H, d, J¼10.4 Hz,
H-7s), 1.70–1.75 (1H, m, H-6, H-3n), 1.80 (1H, td,
J¼11.6, 4.2 Hz, H-3x), 2.30–2.36 (1H, m, H-5), 2.68 (1H,
d, J¼3.2 Hz, H-4), 2.72 (1H, s, H-1), 2.90 (1H, dt, J¼11.2,
4.2 Hz, H-2), 11.10 (1H, br s OH); 19F NMR (470.5 MHz,
CDCl3): d ꢀ127.3 (2F, s, CF2), ꢀ123.9 (2F, s, CF2),
ꢀ123.2 (2F, s, CF2), ꢀ122.4 (2F, s, CF2), ꢀ118.3 (1F, dd,
J¼277.3, 14.1 Hz, CF), ꢀ115.9 (1F, s, J¼282.0, 14.1 Hz,
CF),ꢀ81.9 (3F, t, J¼9.4 Hz, CF3); 13C NMR (125.8 MHz,
CDCl3): d 27.9 (s, C-6), 33.5 (s, C-3), 38.3 (s, C-4), 39.5
(s, C-7), 40.5 (s, C-1), 43.5 (t, J¼20 Hz, C-5), 45.2 (s,
C-2), 106.7–121.7 (m, C6F13), 180.5 (s, C]O); HRMS
calcd for C14H11F13IO2: 458.0551, found: 458.0559.
3.4.3. 6-exo-Heptafluoroisopropyl-5-endo-iodo-2-exo-
methyl-bicyclo[2.2.1]heptane-2-endo-carboxylic acid
(5eo). White solid. Mp: 114.9–115.3 ꢃC; IR (KBr): nmax
2500–3500, 1700, 1280, 1220, 1160, 1100, 740, 680 cmꢀ1
;
1H NMR (500 MHz, CDCl3): d 1.42 (3H, s, H-9), 1.53
(1H, ddd, J¼13.7 Hz, J¼4.4, 1.8 Hz, H-3n), 1.74 (2H, dd,
H-7), 2.51 (2H, s, H-4, H-1), 2.57 (1H, dd, JHF¼8.2 Hz,
J¼6.0 Hz, H-6), 2.76 (1H, dd, J¼13.9, 2.2 Hz, H-3x),
4.45–4.50 (1H, m, H-5); 19F NMR (470.5 MHz, CDCl3):
3.4.7. 2-exo-(4-Chloro-1,1,2,2,3,3,4,4-octafluorobutyl)-
4-oxa-tricyclo[4.2.1.03,7]nonan-5-one (7dp). White solid.

10098
F. Wu et al. / Tetrahedron 62 (2006) 10091–10099
Mp: 39.3–40.8 ꢃC; IR (KBr): nmax 2990, 1780 (g-lactone),
1350, 1220 (C–F), 1180, 1140, 1010, 840, 760, 620 cmꢀ1
dd, J¼1176.3, 282.3 Hz, CF2), ꢀ81.5 (3F, t, J¼10.4 Hz,
CF3); 13C NMR (125.8 HMz, CDCl3): d 20.6 (s, C-10),
35.2 (s, C-9), 38.8 (s, C-1), 43.6 (s, C-6), 44.2 (s, C-8),
51.3 (t, C-2), 51.9 (s, C-7), 78.8 (s, C-3), 111.9–133.8 (m,
CF2CF2CF3), 182.0 (s, C-5); HRMS calcd for C12H11F7O2:
320.0647, found: 320.0699.
;
1H NMR (500 MHz, CDCl3): d 1.66 (1H, d, J¼11.8 Hz,
H-8a), 1.81 (1H, d, J¼13.4 Hz, H-9n), 2.07 (1H, d,
J¼13.4 Hz, H-8s), 2.10–2.20 (1H, m, H-9x), 2.37 (1H, t,
J¼18.2 Hz, H-2), 2.65 (1H, dd, J¼11.3, 4.6 Hz, H-6), 2.86
(1H, s, H-1), 3.29 (1H, t, J¼4.6 Hz, H-7), 5.00 (1H, d,
J¼4.8 Hz, H-3); 19F NMR (470.5 MHz, CDCl3): d ꢀ122.0
(2F, m, CF2), ꢀ121.0 (2F, dd, J¼818.8, 282.4 Hz, CF2),
ꢀ114.4 (2F, dd, J¼889.4, 282.4 Hz, CF2), ꢀ69.0 (2F, dd,
J¼282.4, 188.2 Hz, ClCF2); 13C NMR (125.8 MHz,
CDCl3): d 36.0 (s, C-8), 36.2 (s, C-9), 38.0 (s, C-1), 39.0
(s, C-6), 46.6 (s, C-7), 52.0 (t, J¼20 Hz, C-2), 80.6 (s,
C-3), 110.0–125.0 (m, (CF2)4), 180.2 (s, C-5); HRMS calcd
for C12H9ClF8O2: 372.0320, found: 372.0201.
3.4.11. 2-exo-Heptafluoroisopropyl-6-exo-methyl-4-oxa-
tricyclo[4.2.1.03,7]nonan-5-one (7eo). White solid. Mp:
96.6–96.7 ꢃC; IR (KBr): nmax 2980, 1800 (g-lactone),
1300, 1220 (C–F), 1120, 1020, 720 cmꢀ1 1H NMR
;
(500 MHz, CDCl3): d 1.30 (3H, s, H-10), 1.64 (1H, dd,
J¼13.6, 4.2 Hz, H-9x), 1.74 (1H, d, J¼11.8 Hz, H-8s),
1.90 (1H, dd, J¼13.6, 2.2 Hz, H-9n), 1.98 (1H, d, J¼11.7,
1.6 Hz, H-8x), 2.18 (1H, d, J¼33.3 Hz, H-2), 2.78 (1H, s,
H-1), 2.88 (1H, d, J¼4.8 Hz, H-7), 5.00–5.10 (1H, m, H-3);
19F NMR (470.5 MHz, CDCl3): d ꢀ77.0 (3F, m, CF3),
ꢀ73.9 (3F, m, CF3); 13C NMR (125.8 MHz, CDCl3):
d 19.8 (s, C-10), 34.6 (s, C-9), 39.8 (s, C-1), 42.8 (s, C-6),
43.8 (s, C-8), 49.1 (d, C-2), 51.1 (s, C-7), 78.9 (s, C-3),
111.9–133.8 (m, CF(CF3)2), 181.4 (s, C-5); HRMS calcd
for C12H11F7O2: 320.0647, found: 320.0666.
3.4.8. 2-exo-(8-Chloro-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-hexa-
decafluorooctyl)-4-oxa-tricyclo[4.2.1.03,7]nonan-5-one
(7dq). White solid. Mp: 113.5–114.3 ꢃC; IR (KBr): nmax
3000, 1780 (g-lactone), 1350, 1220 (C–F), 1150, 1020,
1
840, 650, 550 cmꢀ1; H NMR (500 MHz, CDCl3): d 1.66
(1H, d, J¼11.7 Hz, H-8a), 1.81 (1H, d, J¼13.5 Hz, H-9n),
2.09–2.20 (2H, m, H-8s, H-9x), 2.37 (1H, t, J¼18.0 Hz, H-
2), 2.66 (1H, dd, J¼11.2, 4.6 Hz, H-6), 2.86 (1H, s, H-1),
3.29 (1H, t, J¼4.5 Hz, H-7), 5.00 (1H, d, J¼4.8 Hz, H-3);
19F NMR (470.5 MHz, CDCl3): d ꢀ122.65 (6F, m,
3ꢂCF2), ꢀ122.40 (4F, m, 2ꢂCF2), ꢀ121.12 (2F, dd,
J¼818.8, 282.4 Hz, CF2), ꢀ114.30 (2F, dd, J¼889.4,
282.4 Hz, CF2), ꢀ69.06 (2F, m, ClCF2); 13C NMR
(125.8 MHz, CDCl3): d 35.3 (s, C-8), 35.6 (s, C-9), 37.3
(s, C-1), 38.3 (s, C-6), 46.0 (s, C-7), 51.4 (t, J¼20 Hz,
C-2), 80.1 (s, C-3), 106.8–124.1 (m, (CF2)8), 179.5 (s, C-5);
HRMS calcd for C16H9ClF16O2: 572.0036, found: 572.0036.
3.4.12. 2-exo-(4-Chloro-1,1,2,2,3,3,4,4-octafluorobutyl)-
6-exo-methyl-4-oxa-tricyclo-[4.2.1.03,7]nonan-5-one
(7ep). White solid. Mp: 58.3–58.4 ꢃC; IR (KBr): nmax 2990,
1780 (g-lactone), 1350, 1200 (C–F), 1120, 1080, 840, 700,
640 cmꢀ1 1H NMR (500 MHz, CDCl3): d 1.25 (3H, s,
;
H-10), 1.63 (1H, dd, J¼13.4, 4.0 Hz, H-8a), 1.72 (1H, d,
J¼11.8 Hz, H-9), 1.89 (1H, dd, J¼13.4, 2.2 Hz, H-8), 2.07
(1H, dd, J¼11.8, 1.7 Hz, H-9), 2.32 (1H, dd, J¼20.3,
16.1 Hz, H-2), 2.82 (1H, s, H-1), 2.89 (1H, d, J¼5.0 Hz,
H-7), 4.95 (1H, d, J¼5.0 Hz, H-3); 19F NMR (470.5 MHz,
CDCl3): d ꢀ122.1 (2F, m, CF2), ꢀ120.9 (2F, dd, J¼846.9,
291.7 Hz, CF2), ꢀ114.3 (2F, dd, J¼964.5, 272.9 Hz, CF2),
ꢀ69.0 (2F, dd, J¼296.4, 178.8 Hz, ClCF2); 13C NMR
(125.8 MHz, CDCl3): d 20.0 (s, C-10), 34.5 (s, C-9), 38.2
(s, C-1), 42.9 (s, C-6), 43.5 (s, C-8), 51.1 (t, C-2), 51.6 (s,
C-7), 78.3 (s, C-3), 107.4–124.4 (m, (CF2)4), 181.4 (s, C-5);
HRMS calcd for C13H11ClF8O2: 386.0320, found: 386.0336.
3.4.9. 2-exo-Tridecafluorohexyl-4-oxa-tricyclo[4.2.1.03,7]-
nonan-5-one (7ds). White solid. Mp: 84.6–85.2 ꢃC; IR
(KBr): nmax 3000, 1780 (g-lactone), 1350, 1240, 1210
1
(C–F), 1150, 1050, 1020, 980, 700, 650 cmꢀ1; H NMR
(500 MHz, CDCl3): d 1.66 (1H, d, J¼11.7 Hz, H-8a), 1.81
(1H, d, J¼13.4 Hz, H-9n), 2.08 (1H, d, J¼12.4 Hz, H-8s),
2.12 (1H, dd, J¼13.7 Hz, H-9x), 2.37 (1H, t, J¼18.1 Hz,
H-2), 2.66 (1H, dd, J¼11.3, 4.6 Hz, H-6), 2.86 (1H,
s, H-6), 3.29 (1H, t, J¼4.5 Hz, H-7), 5.00 (1H, d, J¼4.8 Hz,
H-3); 19F NMR (470.5 MHz, CDCl3): d ꢀ127.2 (2F, dd,
J¼413.6, 282.0 Hz, CF2), ꢀ123.8 (2F, dd, J¼310.2,
188.0 Hz, CF2), ꢀ122.8 (4F, m, 2ꢂCF2), ꢀ114.3 (2F, dd,
J¼813.1, 282.0 Hz, CF2), ꢀ81.8 (3F, m, CF3); 13C NMR
(125.8 MHz, CDCl3): d 34.8 (s, C-8), 35.1 (s, C-9), 36.8 (s,
C-1), 37.8 (s, C-6), 45.5 (s, C-7), 50.9 (t, J¼20 Hz, C-2),
79.6 (s, C-3), 108.4–125.0 (m, (CF2)5CF3), 179.0 (s, C-5);
HRMS calcd for C14H9F13O2: 456.0395, found: 456.0397.
Acknowledgements
The authors indebted the National Natural Science Founda-
tion of China and the Shanghai Science and Technology
Committee for the financial support (Grant No. 29902001
and 03QB14012).
Supplementary data
1H NMR, 19F NMR, 13C NMR, and 2D NMR spectra for
some new compounds; crystallographic information files
are in CIF format for 5eo, 5cp, 6cp, and 5ds. Supplementary
data associated with this article can be found in the online
version, at doi:10.1016/j.tet.2006.08.042.
3.4.10. 2-exo-Heptafluoroisopropyl-6-exo-methyl-4-oxa-
tricyclo[4.2.1.03,7]nonan-5-one (7en). White solid. Mp:
65.0–65.4 ꢃC; IR (KBr): nmax 2980, 1780 (g-lactone),
1350, 1230 (C–F), 1120, 1020, 740 cmꢀ1 1H NMR
;
(500 MHz, CDCl3): d 1.25 (3H, s, H-10), 1.63 (1H, dd,
J¼13.5, 4.0 Hz, H-9x), 1.72 (1H, d, J¼11.8 Hz, H-8s),
1.90 (1H, dd, J¼13.5, 2.2 Hz, H-9n), 2.07 (1H, dd,
J¼11.8, 1.6 Hz, H-8x), 2.31 (1H, dd, J¼19.3, 17.1 Hz,
H-2), 2.82 (1H, s, H-1), 2.89 (1H, d, J¼5.0 Hz, H-7), 4.95
(1H, d, J¼5.0 Hz, H-3); 19F NMR (470.5 MHz, CDCl3):
d ꢀ127.0 (2F, dd, J¼705.8, 282.3 Hz, CF2), ꢀ115.2 (2F,
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