Cyclization of Hindered Fluorinated Dichloro(5- And 6-)alkenyl Radicals. Structural Effects of Olefins on the Selective Formation of 5-exo and 6-endo Cyclization Products

Article abstract of DOI:10.1021/jo970639u

Reaction of 3-butenyl radicals generated by photolysis of variously substituted Barton esters (both open-chain 1a-d and cyclohexyl 1e-h) with CF₂=CCl₂ gave a mixture of cyclized products (cyclopentanes 6 and 8 and cyclohexanes 7 and 9) as well as noncyclized products (4 and 5) in various ratios depending on the substitution pattern at the olefinic moiety. The product ratios of [cyclization (6 + 7 + 8 + 9):noncyclization (5)] for 1 with more alkyl substituents on the CC double bond were greater than those for 1 with fewer substituents. The products ratio of [5-exo (6 + 8): 6-endo (7 + 9)] was influenced by a steric effect. Photoreaction of Barton ester 2 with CF₂=CCl₂ gave a mixture of cyclohexanes 16 and 17 as well as noncyclized 14 and 15. Dehydrochlorination of decalins 7g and 7h followed by oxidation of sulfide and [2,3]sigmatropic rearrangement of the allyl sulfoxide gave octahydronaphthalenones 23 and 27, respectively.

Full text of DOI:10.1021/jo970639u

7192
J . Org. Chem. 1997, 62, 7192-7200
Cycliza tion of Hin d er ed F lu or in a ted Dich lor o(5- a n d 6-)a lk en yl
Ra d ica ls. Str u ctu r a l Effects of Olefin s on th e Selective F or m a tion
of 5-exo a n d 6-en d o Cycliza tion P r od u cts
Takashi Okano, Hidemasa Ishihara, Nobuyuki Takakura, Hiroyasu Tsuge, Shoji Eguchi,* and
Hiroshi Kimoto†
Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University,
Furo-cho, Chikusa-ku, Nagoya 464-01, J apan, and National Industrial Research Institute of Nagoya,
Hirate-cho, Kita-ku, Nagoya 462, J apan
Received April 9, 1997X
Reaction of 3-butenyl radicals generated by photolysis of variously substituted Barton esters (both
open-chain 1a -d and cyclohexyl 1e-h ) with CF2dCCl2 gave a mixture of cyclized products
(cyclopentanes 6 and 8 and cyclohexanes 7 and 9) as well as noncyclized products (4 and 5) in
various ratios depending on the substitution pattern at the olefinic moiety. The product ratios of
[cyclization (6 + 7 + 8 + 9):noncyclization (5)] for 1 with more alkyl substituents on the CC double
bond were greater than those for 1 with fewer substituents. The products ratio of [5-exo (6 + 8):
6-endo (7 + 9)] was influenced by a steric effect. Photoreaction of Barton ester 2 with CF2dCCl2
gave a mixture of cyclohexanes 16 and 17 as well as noncyclized 14 and 15. Dehydrochlorination
of decalins 7g and 7h followed by oxidation of sulfide and [2,3]sigmatropic rearrangement of the
allyl sulfoxide gave octahydronaphthalenones 23 and 27, respectively.
The C-C bond-forming reactions via carbon radical
hydrolysis or methanolysis with AgNO3.5 Among the
various Barton esters used, we obtained a complex
mixture of radical products from Barton ester of 5-pen-
tenoic acid (1a ). This result was due to contamination
by cyclized products accompanying the major noncyclized
radical addition products, and 6-membered-ring products
were obtained in this reaction as well as the usual
5-membered products. We were interested in the forma-
tion of these unusual 6-membered products and also in
the value of this radical cyclization for the synthesis of a
new class of fluorinated cyclic compounds.6,7 We report
here the relationship between the structure of the olefin
moiety of the initially generated 3-butenyl radical and
cyclization selectivity. We also converted the products
of selective cyclization into difluorooctahydronaphtha-
lones.
intermediates are currently some of the most important
methods in the organic syntheses.1 In particular, radical
cyclization has been intensively investigated and applied
to the construction of complex carbocycles, and prefer-
ential 5-exo cyclization has been established for the
cyclization of 5-hexenyl radicals.2 In the case of some
stable and hindered 5-hexenyl radicals, the selectivity
changes to 6-endo cyclization.3
Recently, we developed an alkyl radical addition
pathway to obtain R,R-difluorocarboxylic acids and their
esters via addition of alkyl radicals generated by the
photolysis of thiohydroxamic carboxylic mixed anhydrides
(Barton esters)4 in the presence of CF2dCCl2 followed by
† National Industrial Research Institute of Nagoya.
X Abstract published in Advance ACS Abstracts, October 1, 1997.
(1) (a) Motherwell. W. B.; Crich. D. Best Synthetic Methods, Free
Radical Chain Reactions in Organic Synthesis; Academic Press:
London, 1992. (b) Giese, B. Radicals in Organic Synthesis: Formation
of Carbon-Carbon Bonds; Pergamon: Oxford, 1986. (c) Ramaiah, M.
Tetrahedron 1987, 43, 3541. (d) Curran, D. P. Synthesis 1988, 417
and 489. (e) J asperse, C. P.; Curran, D. P. Chem. Rev. 1991, 91, 1237.
(f) Curran, D. P. Synlett 1991, 63. (g) Malacria, M. Chem. Rev. 1996,
96, 289.
(2) (a) Giese, B.; Kopping, B.; Dickhaut, J .; Thoma, G.; Kulicke, K.
J .; Trach, F. Org. Reactions 1996, 48, 301. (b) Surzur, J .-M. Reactive
Intermediates; Abramovitch, R. A., Ed.; Plenum Press: New York,
1982; Vol. 2, pp 121. (c) Beckwith, A. L.; Ingold, K. U. Rearrangements
in Ground and Exited States; de Mayo, P., Ed.; Academic Press, New
York, 1980; Vol. 1, pp 161.
Resu lts a n d Discu ssion
Barton esters 1a -h and 2 (Chart 1) were obtained by
standard condensation procedures from the correspond-
ing alkenecarboxylic acids and N-hydroxypyridinethione
with dicyclohexylcarbodiimide in yields of 70-98%.4,5
Photoreactions of Barton esters 1a -h and 2 were con-
ducted as described previously:5 a mixture of the Barton
ester and a 10-molar amount of CF2dCCl2 (3) in CH2Cl2
was irradiated with a 500-W tungsten lamp, and the
(3) (a) Schultz, A. G.; Guzzo, P. R.; Nowak, D. M. J . Org. Chem.
1995, 60, 8044. (b) Clive, D. L. J .; Tao, Y.; Khodabocus, A.; Wu, Y-J .;
Angoh, A. G.; Bennet, S.; Boddy, C.; Bordeleau, L.; Kellner, D.; Kleiner,
G.; Middleton, D. S.; Nichols, C.; Richardson, S.; Vernon, P. G. J . Am.
Chem. Soc. 1994, 116, 11275. (c) Schultz, A. G.; Holoboski, M. A.;
Smyth, M. S. J . Am. Chem. Soc. 1993, 115, 7904. (d) Srikrishna, A.;
Sundarababu, G. Tetrahedron Lett. 1991, 47, 481. (e) Bailey, W. F.;
Khanolkar, A. D. Tetrahedron Lett. 1991, 47, 7727. (f) Ward, J . E.;
Keller, B. F. Tetrahedron Lett. 1991, 32, 843. (g) Takano, S.; Suzuki,
M.; Kijima, A.; Ogasawara, K. Tetrahedron Lett. 1990, 31, 2315. (h)
Curran, D.; Chang, C.-T. J . Org. Chem. 1989, 54, 3140. (i) Morikawa,
T.; Nishiwaki, T.; Kobayashi, K. Tetrahedron Lett. 1989, 30, 2407. (j)
Urabe, H.; Kuwajima, I. Tetrahedron Lett. 1986, 27, 1355.
(4) Crich, D. Aldrichimica Acta 1987, 20, 35. Barton, D. H. R.; Zard,
S. Z. Pure Appl. Chem. 1986, 58, 675. Barton, D. H. R.; Samadi, M.
Tetrahedron 1992, 48, 7083. Barton, D. H. R.; Herv, Y.; Potier, P.;
Thierry, J . Tetrahedron 1987, 43, 6127. Barton, D. H. R; Ozbalik, N.;
Vacher, B. Tetrahedron 1988, 44, 3501.
(5) Okano, T.; Takakura, N.; Nakano, Y; Okajima, A. Eguchi, S.
Tetrahedron 1995, 51, 1903. Okano, T.; Takakura, N.; Nakano, Y.;
Eguchi S. Tetrahedron Lett. 1992, 33, 3491.
(6) For the recent review of synthesis of difluoromethylene com-
pounds, see: Uneyama, K. J . Synth. Org. Chem. J pn. 1993, 51, 232.
For the reviews of biological activities of fluorinated compounds, see:
Welch, J . T. Selective Fluorination in Organic and Bioorganic Chem-
istry; ACS Symposium Series 456; American Chemical Society: Wash-
ington, DC, 1991. Welch, J . T.; Eswarakrishnan, S. Fluorine in
Bioorganic Chemistry; J ohn Wiley & Sons: New York, 1990. Welch,
J . T. Tetrahedron 1987, 16, 381.
(7) Some examples of radical cyclization reactions of difluorometh-
ylene-containing alkenyl radicals leading to 5-exo cyclization were
reported: (a) Arnone, A.; Bravo, P.; Caviccho, M.; Frigerio, M.; Viani,
F. Tetrahedron 1992, 48, 8523. (b) Morikawa, T.; Kodama, Y.; Uchida,
J .; Takano, M.; Washio, Y.; Taguchi, T. Tetrahedron 1992, 48, 8915.
(c) Arnone, A.; Bravo, P.; Viani, F. Tetrahedron Asymmetry 1992, 2,
399. (d) Barth, F.; O-Yang, C. Tetrahedron Lett. 1991, 32, 5873.
S0022-3263(97)00639-7 CCC: $14.00 © 1997 American Chemical Society

Cyclization of Hindered Fluorinated Alkenyl Radicals
J . Org. Chem., Vol. 62, No. 21, 1997 7193
Ta ble 1. P h otor ea ction of Ba r ton Ester s 1a -h w ith Olefin 3
product ratios
5-membered/6-membered
Barton
ester
cyclic/acyclic
entry
products (% yield)a
[(6 + 7 + 8 +9)/5]
[(6 + 8)/(7 + 9)]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
4a (26), 5a (35), 6a (13), 7a (4), 8a (8), 9a (4)
4b (11), 5b (5), 6be (34), 6bt (6), 7b (8), 8b (7), 9b (7)
4c (19), 5c (trace), 6c (53), 8c (6)
4d (19), 5d (22), 7d (38), 9a (10)
4e (13), 5e (68)
45/55
93/7
72/28
76/24
>99/1
<1/99
>99/1
69/32
<1/99
77/23
87/13
88/12
4f (18), 5f (14), 6f (25), 8f (23)
>99/1
<1/99
<1/99
1g
1h
4g (23), 5g (8), 7g (54)b
4h (14), 5h (7), 7h (52)
a
Yields are isolated ones except for the yields of the combinations of 8a and 9a , 8b and 9b, and 5g, which were roughly estimated from
the obtained amounts of the mixtures based on the 1H NMR spectra (8b and 9b, and 5g) or the 13C NMR spectrum (8a and 9a ). See the
b
Experimental Section. 86:14 mixture of cis/ trans products.
Ch a r t 1
adducts 6a or 7a , respectively. However, since cyclized
radicals 12a and 13a are again nucleophilic radicals,
trapping with 3 occurs to yield the cyclized 1:2 adducts
8a and 9a , respectively.
The products from Barton esters 1b-h are sum-
marized in Charts 2 and 3 and Table 1. The structures
of the products were determined as with the products
from 1a . In Table 1, the yields of the products and the
ratios of cyclic and acyclic products and 5- and 6-mem-
bered products are summarized. Although methyl sub-
stitution at the end of the CC double bond (entry 2) has
little effect on cyclopentane/cyclohexane selectivity [from
72 (6a + 8a ):28 (7a + 9a ) to 76 (6b + 8b):24 (7b+ 9b)],
the relative yield of cyclic products increased from 45 (6a
+ 7a + 8a + 9a ):55 (5a ) to 93 (6b + 7b + 8b + 9b):7
(5b) with an increase in the electron density of the CC
double bond. The stereochemistry of 6bt and 6be was
1
1′-H3
1′-H3
determined by the H-NMR coupling constants J H
11 Hz as a trans-coupling for erythro-6be, and J H
)
)
7 Hz, as gauche-coupling for threo-6bt, respectively.
Similarly, the trans-stereochemistry of 7b was deter-
mined by the 1H-NMR coupling constant (J H -H ) 12 Hz),
which indicated axial-axial coupling. Although 1:2
adducts 8b and 9b were obtained as a mixture, a similar
analysis of the 1H-NMR spectrum suggested the same
stereoselectivity. The diastereoselective formation of
6b-9b in the acyclic radical reaction system for 6be and
8b and in the substituted cyclohexyl radicals for 7b and
9b is in accordance with the previously reported selective
formation of radical products.8,9 The preferential cycliza-
tion was enhanced by substitution of another methyl
group on the CC double bond, and nearly complete
cyclization was observed in the reaction of 1c. Further-
more, a steric effect prevents the unfavorable 6-endo
cyclization to cyclohexane derivatives, and 5-membered
products 6c and 8c were obtained selectively. As shown
above, the cyclization of dichloroalkenyl radical interme-
diates occurs at the less-substituted carbon of the π-bond.
In the case of 1d , since the terminal carbon is unhin-
dered, the resulting cyclization products are cyclohexanes
3
4
products were separated by silica gel chromatography.
Some of the cyclization products were inseparable, and
1
their structures were assigned by their H- and 13C-NMR
spectra.
The analyzed products of the reaction of 1a and 3 are
the self-trapping product of the butenyl radical (4a , 26%),
the uncyclized addition product (5a , 35%), cyclopentane
(6a , 13%), cyclohexane (7a , 4%), and an inseparable
mixture of 8a and 9a (12%; 8a :9a ) 2:1). The structures
of 4a and 5a were readily determined by their 1H- and
13C-NMR spectra, in which signals of the butenyl group
were observed, indicating no cyclization. In the 1H-NMR
spectrum of 6a , a pair of doublet-of-doublets peaks in the
lower field revealed the existence of an exocyclic CH2SPy
group in the cyclopentane structure of 6a . Similarly, the
cyclohexane structure of 7a was determined by its 1H-
NMR spectrum, in which a triplet-of-triplets (J ) 13 and
4 Hz) in the lower field reflected the usual axial-axial
and axial-equatorial proton couplings of cyclohexane.
GC-MS analysis and elemental analysis of the mixture
of 8a and 9a supported the notion that both components
have the formula C13H11Cl4F4NS. On the basis of the
(8) Porter, N. A.; Giese, B.; Curran, D. P. Acc. Chem. Res. 1991, 24,
296. Giese, B.; Carboni, B.; Go¨bel, T.; Muhn, R.; Wetterich, F.
Tetrahedron Lett. 1992, 33, 2673. Giese, B.; Damm, W.; Wetterich,
F.; Zeitz, H.-G. Tetrahedron Lett. 1992, 33, 1863. Tanabe, Y.;
Wakimura, K.; Nishii, Y. Tetrahedron Lett. 1996, 37, 1837. Hassler,
C.; Batra, R.; Giese, B. Tetrahedron Lett. 1995, 36, 7639. Guidon, Y.;
Yoakin, C; Lemieux, R.; Boisvert, L.; Delorme, K.; Lavalle´e, J .-F.
Tetrahedron Lett. 1990, 31, 2845. Durkin, K.; Liotta, D.; Rancourt,
J .; Lavallle´e, J .-F.; Boisvert, L.; Guidon, Y. J . Am. Chem. Soc. 1992,
114, 4912. Ku¨ndig, E. P.; Xu, L.-H.; Romanens, P. Tetrahedron Lett.
1995, 36, 4047. Curran, D. P.; Geib, S. J .; Kuo, L. H. Tetrahedron
Lett. 1994, 35, 6235.
1
similarity of this H-NMR spectrum to those of 6a and
7a , these were determined to be cyclized 1:2 adducts. The
reaction is summarized in Scheme 1. Photolytically
generated butenyl radical 10a reacts with 3, to form an
intermediate dichloroalkyl radical 11a , and with 1a , to
give self-trapping product 4a . The electron-deficient
radical 11a gives adduct 5a without cyclization and
secondary intermediates 12a and 13a after cyclization.
Trapping of 12a or 13a with 1a affords cyclized 1:1
(9) Damm, W.; Giese, B.; Hartung, J .; Hasskerl, T.; Houk, K. N.;
Hueter, O.; Zipse, H. J . Am. Chem. Soc. 1992, 114, 4067. Giese, B.
Angew. Chem., Int. Ed., Engl. 1989, 28, 969.

7194 J . Org. Chem., Vol. 62, No. 21, 1997
Okano et al.
Sch em e 1
Ch a r t 2
Ch a r t 3
pseudo-equatorial and pseudo-axial conformers (eq 1) in
7d and 9d . However, since 6-endo cyclization is kineti-
cally unfavorable, the relative yield of the cyclic products
7d and 9d is lower than that in the reaction of 1b in
which the olefin also has two alkyl substituents.
Cyclohexanes and cyclohexenes have rather rigid
conformations, and a higher selectivity of cyclization is
expected. Such cyclization products may be important
for the synthesis of fluorinated polycyclic compounds.
Thus, several Barton esters with unsaturated cyclohex-
ane moieties (1e-h ) were prepared and the photoreaction
with fluoroolefin 3 was examined. Photoreaction of
3-cyclohexenyl derivative 1e gave no cyclized products.
Cyclohexyl radicals react at the less-hindered site with
sterically crowded radical acceptors such as 3 to give
equatorially substituted adducts.9,10 A similar stereo-
chemistry for the cyclohexenyl radicals is anticipated, and
the pseudo-equatorial dichlorodifluoroethyl radical 11e
is a conceivable intermediate. Interconversion between
such a bulky substituent would be too slow for transan-
nular cyclization, and rapid trapping of 11e with the
thiocarbonyl group of 1e gives 5e, while transannular
cyclization of 4-cyclohexenylethyl radicals have been
reported to yield a bicyclo[3.2.1]octane system.11
Barton ester 1f selectively gave 5-exo cyclization
products 6f and 8f as well as noncyclized 5f. The proton
noise-decoupled 13C-NMR spectra indicated stereoselec-
tive formation with 14 signals (10 singlets, three doublets-
of-doublets, and one doublet) for 6f and 16 signals (seven
singlets, five doublets of doublets, two triplets, and two
doublets) for 8f. However, the 1H-NMR spectra (500
MHz) of the cyclized products did not represent their
(11) Chow, Y. L.; Perry, R. A. Can. J . Chem. 1985, 63, 2203.
Weinges, K.; Reichert, H.; Huber-Patz, U.; Irngartinger, H. Liebigs
Ann. Chem. 1993, 403. Yadav, V.; Fallis, Can. J . Chem. 1991, 69, 779.
Kraus, G. A.; Liras, S. Tetrahedron Lett. 1990, 31, 5265.
(10) Okano, T.; Nakano, Y.: Takakura, N.; Eguchi, S. The 50th
Anniversary International Symposium on Organic Synthesis; abstract
PS-32; Soc. Synth. Org. Chem.: Tokyo, 1992.

Cyclization of Hindered Fluorinated Alkenyl Radicals
J . Org. Chem., Vol. 62, No. 21, 1997 7195
F igu r e 2. ORTEP plot of trans-7g.
F igu r e 1. ORTEP plot of 8f.
structures in a straigtforward manner. A quartet signal
(J ) 4 Hz) in the lower field region (δ 4.69) of 6f reveals
its hydroindane skeleton, since this signal can be as-
signed to the proton at the thiopyridyl-substituted car-
bon, which in the 6-endo products would presumably
appear as a triplet due to coupling with only two vicinal
hydrogens. The small coupling constant suggests that
this thiopyridyl group occupies an axial position. Inter-
conversion between pseudo-equatorial and pseudo-axial
conformers is no longer necessary for the cyclization of
the radical intermediate, since the distance from the
radical center to the olefin in intermediate 11f is shorter
F igu r e 3. ORTEP plot of 7h .
Sch em e 2
than that in 11e. However, 1,3-transannular cyclization
is unlikely to occur because of the expected increase in
strain. The 1:2 adduct 8f was crystallized, and X-ray
crystallographic analysis revealed its stereochemistry as
shown in Figure 1. Thus, the cis-hydrindane structure12
of 6f can be reasonably inferred from the structure of 8f
according to the same intermediacy of the 4-hydrindanyl
radical to give both 6f and 8f. The dichlorodifluorothio-
pyridylethyl group in 8f actually occupies an axial
position of the cyclohexane ring, like the thiopyridyl
1
group in 6f, as assigned by the H-NMR spectrum.
radical intermediate 11g in the reaction of 1g cyclizes
via a pseudo-equatorially substituted transition state to
give a “flat” tertiary radical 13g, and radical chain
transfer then occurs by reaction with the thiocarbonyl
group in 1g, which approaches from the axial direction
of the radical center. However, cyclization of 11h occurs
via an axially substituted conformation, since the maxi-
mum overlap between the radical center and the CC
π-bond leads to a “bent” tertiary radical 13h , in which
the thiocarbonyl group of 1h approaches from the axial
direction of the radical center. These stereochemical
consideration are consistent with 2-substituted cyclohexyl
radicals,9,10 even though the selective formation of trans-
decalin from a related alkenyl radical has been re-
ported.14 It is noteworthy that the tertiary carbon
radicals 13g and 13h did not give 1:2 adducts because
of the higher steric hindrance around the radical center.
The thiocarbonyl group, which is a less crowded radical
acceptor, was the only trapping agent for these radicals.
The radical reaction of 2 derived from 5-hexenoic acid
was also examined, and again a relatively complex
Selective 6-endo cyclization was also observed in the
1
reaction of 1g.13 In this case, the H NMR spectrum of
the saturated product 7g clearly shows a decalin struc-
ture by the absence of the lower-field signal which is
1
expected in the 5-exo product. According to the H- and
13C-NMR spectra, 7g is a 86:14 mixture of diastereomers.
The major product was crystallized and the trans-decalin
structure was established by X-ray crystallography (Fig-
ure 2). Similarly, selective 6-endo cyclization of 1h to
7h is supported by the 1H-NMR spectrum, and the
contrasting cis-decalin structure was also verified by
X-ray crystallography (Figure 3). The 13C-NMR spectrum
of 7h revealed its highly stereoselective formation, since
no stereochemical counterpart was detected. This dra-
matic change in stereochemistry can be explained as
schematically shown in Scheme 2. The initially formed
(12) Stereoselective formation of cis-hydrindane from cyclohexenyl-
propyl radical has been reported: Curran, D. P.; Qi, H.; DeMello, N.
C.; Lin, C.-H. J . Am. Chem. Soc. 1994, 116, 8430.
(13) In the reaction mixture, 3% yield of [4,4-dichloro-3,3-difluoro-
4-(2-pyridylthio)butylidene]cyclohexane was found as an inseparable
component of the mixture with 5g. This 1:1 adduct was derived from
the inseparable impurity contained in the starting cyclohexene-1-
propionic acid. See the experimental section.
(14) Kawaguchi, M.; Satoh, S.; Mori, M.; Shibasaki, M. Chem. Lett.
1992, 395.

7196 J . Org. Chem., Vol. 62, No. 21, 1997
Okano et al.
Sch em e 3
Sch em e 4
mixture was obtained (Scheme 3). After chromatographic
separation, self-trapping product 14 (7%), acyclic 1:1
adduct 15 (49%), 6-exo cyclization product 16 (14%), and
6-exo cyclization 1:2 adduct 17 (12%) were identified. The
relative yield of the cyclized products [(16 + 17)/15 )
0.53] is much smaller than that in the reaction of 1a
(0.82), indicating that cyclization of 6-heptenyl radicals
is relatively less favorable.15 Since the relative yields of
the cyclization products were far lower than with the
3-butenyl radical, the substituent effect was not inves-
tigated further.
Alkyl-substituent effects in the radical cyclization of
5-hexenyl radicals have been extensively investigated,
and the regiochemistry of the bonding terminal of a
radical is known to be strongly affected by the alkyl
substituents.2 The regioselectivities of stable carbon
radicals conjugated with electron-deficient groups change
from kinetically controlled 5-exo cyclization to thermo-
dynamically controlled 6-endo cyclization.16 Although
chlorine-substitution may stabilize the carbon radical, the
majority of 5-exo products in the reaction of 1a suggests
the usual kinetic control of radical cyclization, as in the
5-exo cyclization of other dichloromethyl radicals.17 Rela-
tive and absolute reaction rates of radical cyclization have
been measured for the 5-hexenyl radicals with varous
substituents on the vinyl group.2c,18 It is interesting that
the increase in 6-endo products in the radical cyclization
of 5-substituted hexenyl radicals is not caused by the
acceleration of 6-endo cyclization but rather by the
reduction in the rate of 5-exo cyclization. Thus, under
competitive reaction conditions, such as in the photode-
composition of Barton esters 1 in the presence of olefin
3, the ratios of cyclized products to noncyclized addition
products would be unchanged or smaller when the 6-endo
products are predominant, since the reaction rates of
linear radicals 11 with the thiocarbonyl group of the
starting material would be comparable for the various
substitution patterns of the olefinic moiety. However,
the results described above show that the relative rates
of cyclization are accelerated in the case of more-
substituted olefins. Unlike the hexenyl radical, chlori-
nated radicals 11a -h are highly electron-deficient, and
substitution on the vinyl group with alkyl groups makes
cyclization more favorable. While this acceleration may
occur in both the 5-exo and 6-endo processes, the large
steric effect of the bulky dichlorodifluoroalkyl radical and
the substituted olefinic carbon center cancels the elec-
tronic effect and also determines the regiochemistry of
the cyclization.
Con ver sion of R a d ica l Ad d u ct s 7g a n d 7h t o
Diflu or oocta lon es. Radical adducts like 5 were con-
verted to the corresponding difluorocarboxylic acids by
hydrolytic treatment with AgNO3.5 Similar treatment
of the cyclized products 7g and 7h that were obtained in
relatively good yields was expected to give products with
a gem-difluorooctahydronaphthalenone structure. How-
ever, similar reaction conditions were completely inef-
fective against 7g because two fluorine atoms prevented
the generation of chlorinated carbocation at the R-posi-
tion, where a π-participation effect by the thiopyridyl
moiety is no longer available. Thus, we developed a new
procedure for converting 7g and 7h to the fluorinated
cycloalkenones (Scheme 4). Dehydrochlorination of 7g
was carried out with Na2S‚9H2O-KOH in refluxing
EtOH to give 22 in 83% yield, and no dehydrofluorination
was observed. Oxidation of the thioether group of 22
with m-CPBA at low temperature gave the desired 2,2-
difluoro-1,2,3,4,5,6,7,8-octahydronaphthalen-1-one (23) in
(15) The 6-exo cyclization of heptenyl radical is 100 times slower
than the 5-exo cyclization of hexenyl radical: Beckwith, A. L. J .;
Schiesser, C. H., Tetrahedron 1985 42, 3925. Beckwith, A. L. J .
Tetrahedron 1981, 37, 3073.
(16) J ulia, M.; Le Goffic, F.; Katz, L. Bull. Soc. Chim. Fr. 1964, 1122.
J ulia, M.; Le Goffic, F. Bull. Soc. Chim. Fr. 1964, 1129.
(17) Nagashima, H.; Seki, K.; Ozaki, N.; Wakamatsu, H.; Itoh, K.;
Tomo, Y.; Tsuji, J . J . Org. Chem. 1990, 55, 985. Nagashima, H.; Ozaki,
N.; Ishii, M.; Seki, K.; Washiyama, M.; Itoh, K. J . Org. Chem. 1993,
58, 464. Nagashima, H.; Ozaki, N.; Seki, K.; Ishii, M.; Itoh, K. J . Org.
Chem. 1989, 54, 4497. Takano, S.; Nishizawa, S.; Akiyama, M.;
Ogasawara, K. Synthesis 1984, 949.
(18) Van Tilborg, W. J . M.; Schaafsman, S. E.; Steinberg, H.; DeBoer,
T. J . Recl. Trav. Chim. Pay-Bas 1967, 86, 417.

Cyclization of Hindered Fluorinated Alkenyl Radicals
J . Org. Chem., Vol. 62, No. 21, 1997 7197
86% yield via [2,3]sigmatropic rearrangement19 of allyl
sulfoxide 24 to allyl sulfenate 25 followed by hydrolysis
of the R-chlorosulfenate structure under acidic conditions.
Isomeric 7h was also dehydrochlorinated with more basic
potassium tert-butoxide to give 26, which was then
converted into 3,3-difluoro-2,3,4,4a,5,6,7,8-octahydronaph-
thalen-2-one (27) in good yield. These conversions of the
radical reaction products into fluorinated cyclohexenones
may be useful for the synthesis of fluorine-containing
biologically active fused cyclohexenone compounds, such
as steroids.
1,1-Dich lor o-2,2-d iflu or o-5-(2-p yr id ylt h io)cycloh ex-
a n e (7a ): 48 mg (4%); pale yellow oil; H-NMR (CDCl3, 500
1
MHz) 1.82 (1H, qd, J ) 14, 4 Hz), 2.21-2.30 (2H, m), 2.47
(1H, tdd, J ) 14, 7, 2 Hz), 2.53-2.60 (1H, m), 3.04 (1H, dddd,
J ) 14, 5, 4, 3 Hz), 4.28 (1H, tt, J ) 14, 4 Hz), 7.03 (1H, ddd,
J ) 8, 5, 1 Hz), 7.16 (1H, dt, J ) 8, 1 Hz), 7.51 (1H, td, J ) 8,
2 Hz), 8.46-8.47 (1H, m); 13C-NMR (CDCl3) 27.96 (d, J ) 9
Hz), 30.63 (dd, J ) 25, 22 Hz), 37.67, 49.00, 86.26 (dd, J ) 30,
24 Hz), 119.08 (dd, J ) 257, 247 Hz), 120.38, 123.09, 136.65,
150.23, 157.51; 19F-NMR (CDCl3) -106.2 (ddd, J ) 231, 26,
11 Hz), -110.0 (d, J ) 231 Hz); MS m/z (%) 297 (M+, 41), 299
(15), 111 (100). Anal. Calcd for C11H11Cl2F2NS: C, 44.31; H,
3.72; N, 4.77. Found: C, 44.50; H, 3.74; N, 4.49.
1:1 Mixtu r e of 1,1-Dich lor o-2,2-diflu or o-5-[3,3-dich lor o-
2,2-d iflu or o-3-(2-p yr id ylt h io)p r op yl]cyclop en t a n e (8a )
a n d 5-[2,2-Dich lor o-1,1-d iflu or o-2-(2-p yr id ylth io)eth yl]-
1,1-d ich lor o-2,2-d iflu or ocycloh exa n e (9a ): 202 mg (12%:
8a ; 8%, 9a ; 4%: Yields were estimated from the relative
intensities of the paired peaks in the 13C-NMR spectrum); 1H-
NMR (CDCl3) 1.71-3.50 (7H, m), 7.38-7.45 (1H, m), 7.76-
7.90 (2H, m), 8.69-8.73 (1H, m); 13C-NMR (CDCl3) 22.61 (td,
J ) 8, 4Hz), 24.56 (dd, J ) 7, 4 Hz), 29.35 (dd, J ) 25, 21 Hz),
29.53 (t, J ) 24 Hz), 32.68 (t, J ) 22 Hz), 38.96 (t, J ) 23 Hz),
43.67 (m), 45.10, 86.22 (dd, J ) 32, 27 Hz), 92.00 (dd, J ) 29,
24 Hz), 93.90 (t, J ) 32 Hz), 93.98 (t, J ) 34 Hz), 118.67 (dd,
J ) 257, 247 Hz), 120.26 (t, J ) 248 Hz), 125.25, 122.26 (t, J
) 258 Hz), 125.61 (t, J ) 252 Hz), 132.41, 132.58, 137.79,
151.11, 151.74; 19F-NMR (CDCl3) -94.2 (0.7F, dt, J ) 221, 26
Hz), -100.4 to -102.1 (2F, m), -104 to -102 (0.6F, m),
-115.84 (0.7F, dd, J ) 221, 7 Hz); MS m/z (%) 429 (M+, 2), 78
(100). Anal. Calcd for C13H11Cl4F4NS: C, 36.22; H, 2.57; N
3.25. Found: C, 36.32; H, 2.70; N, 3.00.
Exp er im en ta l Section
1H- and 13C-NMR spectra of CDCl3 solution were recorded
in ppm (δ) at 200 and 50 MHz, respectively, with TMS as an
internal standard if not noted otherwise. 19F-NMR spectra of
CDCl3 solution were recorded at 87.67 MHz. Chemical shifts
of the 19F-NMR spectra were reported in ppm (δ) relative to
internal CFCl3.
Barton esters 1a -h and 2 were prepared4,5 by condensation
of the corresponding carboxylic acids and N-hydroxy-2-pyri-
dinethione with N,N-dicyclohexylcarbodiimide (DCC): a mix-
ture of a carboxylic acid and equimolar amounts of N-hydroxy-
2-pyridinethione and DCC in CH2Cl2 was stirred at room
temperature for 2-4 h, and the formed dicyclohexylurea was
filtered off in the dark. Removal of the solvent under reduced
pressure gave a practically pure Barton ester in 70-98%
yields. Freshly prepared Barton esters were used as quickly
as possible without further purification.
Gen er a l P r oced u r e for th e P h otor ea ction of Ba r ton
Ester s 1a -h a n d 2 w ith 1,1-Dich lor o-2,2-d iflu or oeth en e
(3). An ice-cooled mixture of Barton ester and 10-fold amount
of 3 in CH2Cl2 in a round-bottom flask equipped with a reflux
condenser, in which -30 °C coolant (EtOH-H2O) was circu-
lated, was irradiated by a 500-W tungsten lamp until the
yellow color of the solution was disappeared. After removal
of the excess 3 by distillation at 30 °C, the solvent was removed
under reduced pressure. The residue was chromatographed
on a SiO2 column eluting with n-hexane-EtOAc.
P h otor ea ction of 1b a n d 3 was performed as above using
1b (339 mg, 1.6 mmol), 3 (1.6 mL, ca. 16 mmol), and CH2Cl2
(2 mL) with irradiation for 5 h.
(E)-1-(2-P yr id ylth io)-3-p en ten e (4b): 30 mg (11%); color-
1
less oil; H-NMR (CDCl3) 1.665 (3H, d, J ) 5 Hz), 2.395 (2H,
m), 3.195 (2H, t, J ) 7 Hz), 5.42-5.65 (2H, m), 6.967 (1H, ddd,
J ) 7, 5, 1 Hz), 7.175 (1H, dt, J ) 8, 1 Hz), 7.471 (1H, ddd, J
) 8, 7, 2 Hz), 8.428 (1H, ddd, J ) 5, 2, 1 Hz).
(E)-1,1-Dich lor o-2,2-d iflu or o-1-(2-p yr id ylt h io)-5-h ep -
ten e (5b): 27 mg (5%); pale yellow oil; 1H-NMR (CDCl3) 1.67
(3H, d, J ) 4.8 Hz), 2.25-2.64 (4H, m), 5.38-5.65 (2H, m),
7.39 (1H, ddd, J ) 7, 5, 1 Hz), 7.79 (1H, dt, J ) 7, 2 Hz), 7.87
(1H, td, J ) 7, 1 Hz), 8.71 (1H, dd, J ) 5, 2 Hz); 13C-NMR
(CDCl3) 17.94, 24.78 (t, J ) 4 Hz), 32.35 (t, J ) 23 Hz), 94.20
(t, J ) 30 Hz), 122.24 (t, J ) 257 Hz), 124.94, 126.94, 129.10,
132.14, 137.64, 151.00, 152.17; 19F-NMR (CDCl3) -104.2 (t, J
) 17 Hz); MS m/z (%) 311 (M+, 1), 111 (100). Anal. Calcd for
C12H13F2Cl2NS: C, 46.17; H, 4.20; N, 4.49. Found: C, 46.17;
H, 4.55; N, 4.14.
P h otor ea ction of 1a a n d 1 was performed as above using
1a (837 mg, 4 mmol), 3 (4 mL, ca. 40 mmol), and CH2Cl2 (2
mL) with irradiation for 5 h.
1-(2-P yr id ylth io)-3-bu ten e (4a ): 172 mg (26%); pale
yellow oil; 1H-NMR (CDCl3) 2.40-2.50 (2H, m), 3.25 (2H, t, J
) 7 Hz), 5.00-5.18 (2H, m), 5.90 (1H, ddt, J ) 17, 10, 7 Hz),
6.95-7.00 (1H, m), 7.16-7.20 (1H, m), 8.44 (1H, br s).
1,1-Dich lor o-2,2-d iflu or o-1-(2-p yr id ylt h io)-5-h exen e
1
(5a ): 417 mg (35%); pale yellow oil; H-NMR (CDCl3) 2.34-
er yth r o-2,2-Dich lor o-1,1-d iflu or o-3-[1-(2-p yr id ylth io)-
eth yl]cyclop en ta n e (6be): 98 mg (34%); colorless solid; mp
2.70 (4H, m), 5.02-5.20 (2H, tq-like m), 5.78-5.98 (1H, m),
7.37-7.43 (1H, m), 7.75-7.83 (1H, m), 7.86-7.90 (1H, m), 8.71
(1H, br s); 13C-NMR (CDCl3) 25.89 (t, J ) 4 Hz), 31.67 (t, J )
25 Hz), 94.43 (t, J ) 32 Hz), 116.24, 122.21 (t, J ) 257 Hz),
124.98, 132.20, 136.63, 137.65, 151.01, 152.09; 19F-NMR
(CDCl3) -104.1 (t, J ) 17 Hz). MS m/z (%) 297 (M+, 1.4), 110
(100). Anal. Calcd for C11H11Cl2F2NS: C, 44.31; H, 3.72, N;
4.77. Found: C, 44.37; H, 3.98; N, 4.38.
1
60-61.5 °C; H-NMR (CDCl3) 1.73 (3H, d, J ) 7 Hz), 1.73-
1.95 (1H, m), 2.03-2.51 (3H, m), 2.73-2.90 (1H, m), 4.29 (1H,
dqd, J ) 11, 7, 1 Hz), 7.01 (1H, ddd, J ) 7, 6, 1 Hz), 7.17 (1H,
dt, J ) 8, 1 Hz), 7.50 (1H, ddd, J ) 8, 7, 2 Hz), 8.05 (1H, ddd,
J ) 6, 2, 1 Hz); 13C-NMR (CDCl3) 21.54, 24.61 (t, J ) 7 Hz),
28.16 (dd, J ) 25, 20 Hz), 43.20, 53.57, 90.10 (dd, J ) 28, 24
Hz), 120.26, 123.54, 126.15 (dd, J ) 268, 251 Hz), 136.62,
150.05, 158.33; 19F-NMR (CDCl3) -95.1 (dt, J ) 226, 25 Hz),
-114.0 (d, J ) 226 Hz); MS m/z (%) 311 (M+, 9), 111(100).
Anal. Calcd for C12H13F2Cl2NS: C, 46.17; H, 4.20; N, 4.49.
Found: C, 46.30; H, 4.37; N, 4.19.
1,1-Dich lor o-2,2-d iflu or o-5-[1-(2-p yr id ylt h io)m et h yl]-
cyclop en ta n e (6a ): 155 mg (13%); pale yellow oil; H-NMR
1
(CDCl3, 500 MHz) 1.64-1.88 (1H, m), 2.05-2.57 (3H, m),
2.83-3.01 (1H, m), 3.26 (1H, dd, J ) 14, 10 Hz), 3.82 (1H, dd,
J ) 14, 4 Hz), 7.01 (1H, ddd, J ) 7, 4, 1 Hz), 7.19 (1H, dt, J )
7, 1 Hz), 7.50 (1H, td, J ) 7, 1 Hz), 8.45 (1H, br d); 13C-NMR
(CDCl3) 23.55 (d, J ) 6 Hz), 29.07 (dd, J ) 25, 21 Hz), 29.54,
49.60, 91.72 (dd, J ) 28, 24 Hz), 120.10, 122.59, 125.94 (dd, J
) 268, 253 Hz), 136.48, 150.03, 158.22; 19F-NMR (CDCl3) -94.4
(dt, J ) 220, 23 Hz), -113.4 (d, J ) 220 Hz); MS m/z (%) 297
(M+, 31), 111 (100). Anal. Calcd for C11H11Cl2F2NS: C, 44.31;
H, 3.72; N, 4.70. Found: C, 44.15; H, 3.70; N, 4.88.
th r eo-2,2-Dich lor o-1,1-d iflu or o-3-[1-(2-p yr id ylth io)eth -
yl]cyclop en ta n e (6bt): 17 mg (6%); pale yellow oil; 1H-NMR
(CDCl3) 1.54 (3H, d, J ) 7 Hz), 1.78-2.00 (1H, m), 2.03-2.59
(3H, m), 2.89-3.04 (1H, m), 4.36 (1H, p, J ) 7 Hz), 7.00 (1H,
ddd, J ) 7, 5, 1 Hz), 7.20 (1H, dt, J ) 8, 1 Hz), 7.50 (1H, ddd,
J ) 8, 7, 2 Hz), 8.45 (1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR (CDCl3)
19.69, 22.34 (d, J ) 7 Hz), 28.53 (dd, J ) 25, 21 Hz), 39.67,
52.89, 91.00 (dd, J ) 27, 24 Hz), 120.05, 123.57, 125.84 (dd, J
) 267, 252 Hz), 136.47, 149.91, 158.54; 19F-NMR (CDCl3) -94.6
(dt, J ) 215, 26 Hz), -114.4 (d, J ) 215 Hz); MS m/z (%) 311
(M+, 17), 111 (100). Anal. Calcd for C12H13F2Cl2NS: C, 46.17;
H, 4.20; N, 4.49. Found: C, 46.18; H, 4.38; N, 4.42.
(19) Reich, H. J .; Yelm, K. E.; Wollowitz, S. J . Am. Chem. Soc. 1983,
105, 2503. Garigipati, R. S.; Freyer, A. J .; Whittle, R. R.; Weinreb, S.
M. J . Am. Chem. Soc. 1984, 106, 7861. Lambs, L.; Singh, N.;
Biellmann, J .-F. J . Org. Chem. 1992, 57, 6301.

7198 J . Org. Chem., Vol. 62, No. 21, 1997
Okano et al.
3,4-tr a n s-2,2-Dich lor o-1,1-d iflu or o-3-m et h yl-4-(2-p yr -
id ylth io)cycloh exa n e (7b): 23 mg (8%); colorless solid; mp
92-95 °C; H-NMR (CDCl3) 1.46 (3H, d, J ) 6 Hz), 1.91 (1H,
(2H, t, J ) 7 Hz), 3.30 (2H, t, J ) 7 Hz), 4.79-4.82 (2H, m),
6.98 (1H, ddd, J ) 7, 5, 1 Hz), 7.18 (1H, dt, J ) 8, 1 Hz), 7.48
(1H, ddd, J ) 8, 7, 2 Hz), 8.44 (1H, ddd, J ) 5, 2, 1 Hz).
1,1-Dich lor o-2,2-d iflu or o-5-m eth yl-1-(2-p yr id ylth io)-5-
h exen e (5d ): 249 mg (22%); pale yellow oil; 1H-NMR (CDCl3)
1.79 (3H, s), 2.29-2.37 (2H, m), 2.46-2.74 (2H, m), 4.75-4.81
(2H, m), 7.40 (1H, m), 7.75-7.90 (2H, m), 8.71 (1H, m); 13C-
NMR (CDCl3) 22.57, 29.41 (t, J ) 4 Hz), 30.66 (t, J ) 23 Hz),
94.51 (t, J ) 33 Hz), 111.21, 122.30 (t, J ) 257 Hz), 124.97,
132.19, 137.65, 143.96, 151.00, 152.07; 19F-NMR (CDCl3)
-104.4 (t, J ) 17 Hz); MS m/ z (%) 311 (M+, 3), 78 (100). Anal.
Calcd for C12H13Cl2F2NS: C, 46.17; H, 4.20; N, 4.49. Found:
C, 46.24; H, 4.16; N, 4.52.
2,2-Dich lor o-1,1-d iflu or o-4-m eth yl-4-(2-p yr id ylth io)cy-
cloh exa n e (7d ): 357 mg (38%); colorless solid; mp 69-70 °C;
1H-NMR (CDCl3) 1.70 (3H, s), 1.83-2.01 (1H, m), 2.18-2.59
(3H, m), 2.92 (1H, d, J ) 15 Hz), 3.51 (1H, d, J ) 15 Hz), 7.10
(1H, ddd, J ) 7, 5, 1 Hz), 7.27 (1H, dt, J ) 8, 1 Hz), 7.54 (1H,
ddd, J ) 8, 7, 2), 8.51 (1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR
(CDCl3) 27.86 (t, J ) 23 Hz), 28.31, 34.12 (t, J ) 5 Hz), 49.68,
52.96, 85.58 (t J ) 27 Hz), 119.15 (t, J ) 252 Hz), 121.35,
126.85, 136.76, 150.02, 157.90; 19F-NMR (CDCl3) -107.22 (m);
MS m/z (%) 311 (M+, 25), 67 (100). Anal. Calcd for
C12H13Cl2F2NS: C, 46.17; H, 4.20; N, 4.49. Found: C, 46.54;
H, 4.39; N, 4.31.
2,2-Dich lor o-1,1-d iflu or o-4-m eth yl-4-[2,2-d ich lor o-1,1-
d iflu or o-2-(2-p yr id ylth io)eth yl]cycloh exa n e (9d ): 133 mg
(10%); pale yellow oil; 1H-NMR (CDCl3) 1.73 (3H, s), 1.96-
2.64 (4H, m), 3.07 (1H, dd, J ) 15, 2 Hz), 3.17 (1H, ddd, J )
15, 4, 2 Hz), 7.42 (1H, ddd, J ) 8, 5, 1 Hz), 7.81 (1H, td, J )
8, 2 Hz), 7.88 (1H, dt, J ) 8, 1 Hz), 8.74 (1H, ddd, J ) 5, 2, 1
Hz); 13C-NMR (CDCl3) 20.85, 26.20 (t, J ) 22 Hz), 28.53 (dd,
J ) 14, 7 Hz), 46.93 (t, J ) 22 Hz), 48.55 (t, J ) 5 Hz), 85.24
(dd, J ) 30, 24 Hz), 94.37 (t, J ) 36 Hz), 118.49 (dd, J ) 256,
246 Hz), 121.47 (t, J ) 267 Hz), 125.21, 132.80, 137.73, 151.01,
151.83; 19F-NMR (CDCl3) -102.3 (s), -106.5 (ddd, J ) 238,
25, 7 Hz), -110.6 (d, J ) 238 Hz); MS (CI) m/z (%) 444 (M +
H+, 76), 446 (100). Anal. Calcd for C14H13Cl4F4NS: C, 37.78;
H, 2.94; N, 3.15. Found: C, 38.08; H, 2.95; N, 3.07.
1
qd, J ) 13, 4 Hz), 2.12-2.40 (2H, m), 2.42-2.71 (2H, m), 4.01
(1H, td, J ) 13, 4 Hz), 7.01 (1H, ddd, J ) 7, 5, 1 Hz), 7.18 (1H,
dt, J ) 8, 1 Hz), 7.50 (1H, ddd, J ) 8, 7, 2 Hz), 8.44 (1H, ddd,
J ) 5, 2, 1 Hz); 13C-NMR (CDCl3)20 14.55, 28.99 (d, J ) 8 Hz),
30.43 (dd, J ) 24, 22 Hz), 44.34, 48.64, 119.37 (t, J ) 252, 243
Hz), 120.33, 123.35, 136.74, 149.90, 157.89; 19F-NMR (CDCl3)
-103.7 (d, J ) 232 Hz), -107.2 (dd, J ) 232, 19 Hz); MS m/z
(%) 311 (M+, 30), 111 (100). Anal. Calcd for C12H13F2Cl2NS:
C, 46.17; H, 4.20; N, 4.49. Found: C, 46.37, H, 4.32, N, 4.18.
1:1 Mixtu r e of 2,2-d ich lor o-1,1-d iflu or o-3-[4,4-d ich lor o-
3,3-d iflu or o-4-(2-p yr id ylth io)bu t-2-yl]cyclop en ta n e (8b)
a n d 2,2-Dich lor o-1,1-d iflu or o-3-m eth yl-4-[2,2-d ich lor o-
1,1-d iflu or o-2-(2-p yr id ylth io)eth yl]cycloh exa n e (9b): 100
mg (14%: 8b; 7%, 9b; 7%; yields were estimated from the
relative peak areas of the paired peaks in the 1H-NMR
1
spectrum); colorless oil; H-NMR (CDCl3) 1.51 (1.5H, dd, J )
7, 2 Hz), 1.70 (1.5H, dd, J ) 7, 3 Hz), 1.85-2.52 (4H, m), 2.76-
2.94 (0.5H, m), 3.07-3.36 (1H, m), 3.37-3.66 (0.5H, m), 7.36-
7.40 (1H, m), 7.74-7.90 (2H, m), 8.69-8.72 (1H, m); 13C-NMR
(CDCl3) 12.39 (t, J ) 5 Hz), 15.06 (dd, J ) 9, 4 Hz), 19.31, (d,
J ) 6 Hz), 25.90 (dd, J ) 12, 7 Hz), 28.10 (ddd, J ) 25, 20, 3
Hz), 29.31, (dd, J ) 25, 22 Hz), 36.75 (t, J ) 23 Hz), 42.57 (dd,
J ) 23, 20 Hz), 47.82 (d, J ) 7 Hz), 49.31 (d, J ) 5 Hz), 90.6-
95.6 (m), 116.4-131.0 (m), 125.12, 132.46, 137.69, 137.75,
151.05, 137.69, 137.75; 19F-NMR (CDCl3) -91.9 (d, J ) 246
Hz), -92.7 (dt, J ) 190, 22 Hz), -95.3 (dt, J ) 190, 20 Hz),
-103.9 (dd, J ) 246 Hz), -104.7 (dd, J ) 246, 20 Hz), -114.7
(dd, J ) 170, 7 Hz), 117.3 (d, J ) 170 Hz); MS (CI) m/ z (%)
446 (M + H+, 70), 446 (100). Anal. Calcd for C14H13Cl4F4NS:
C, 37.78; H, 2.94, N, 3.15. Found: C, 37.89; H, 2.92, N, 3.04.
P h otor ea ction of 1c a n d 3 was performed as above using
1c (763 mg, 3.0 mmol), 3 (3.0 mL, ca. 30 mmol), and CH2Cl2
(3 mL) with irradiation for 5 h.
4-Meth yl-1-(2-pyr idylth io)-3-pen ten e (4c): 120 mg (19%);
1
pale yellow oil; H-NMR (CDCl3) 1.63 (3H, d, J ) 1 Hz), 1.71
(3H, d, J ) 1 Hz), 2.40 (2H, q, J ) 7 Hz), 3.16 (2H, t, J ) 7
Hz), 5.22 (1H, m, J ) 7 Hz for a triplet), 6.98 (1H, ddd, J ) 7,
5, 1 Hz), 7.16 (1H, dt, J ) 8, 1 Hz), 7.47 (1H, ddd, J ) 8, 7, 2
Hz), 8.44 (1H, ddd, J ) 5, 2, 1 Hz).
P h otor ea ction of 1e a n d 3 was performed as above using
1e (1000 mg, 4.25 mmol), 3 (4.0 mL, ca. 40 mmol), and CH2Cl2
(4 mL) with irradiation for 5 h.
4-(2-P yr id ylt h io)cycloh exen e (4e): 107 mg (13%); 1H-
NMR (CDCl3) 1.693-1.874 (1H, m), 2.06-2.28 (4H, m), 2.50-
2.67 (1H, m), 4.04-4.17 (1H, m), 5.63-5.79 (2H, m), 6.97 (1H,
ddd, J ) 8, 5, 1 Hz), 7.18 (1H, dt, J ) 8, 1 Hz), 7.47 (1H, ddd,
J ) 8, 8, 2 Hz), 8.43 (1H, ddd, J ) 5, 2, 1 Hz).
2,2-Dich lor o-1,1-diflu or o-3-[2-(2-p yr id ylth io)pr op-2-yl]-
1
cyclop en ta n e (6c): 546 mg (53%); pale yellow oil; H-NMR
(CDCl3) 1.63 (3H, s), 1.89 (3H, s), 2.06-2.49 (4H, m), 3.82-
3.95 (1H, m), 7.11 (1H, ddd, J ) 7, 5, 1 Hz), 7.29 (1H, dt, J )
8, 1 Hz), 7.54 (1H, td, J ) 8, 2 Hz), 8.50 (1H, ddd, J ) 5, 2, 1
Hz); 13C-NMR (CDCl3) 20.95 (d, J ) 2 Hz), 25.69, 28.03 (dd, J
) 25, 21 Hz), 29.18, 53.60, 54.20, 90.86 (dd, J ) 26, 23 Hz),
121.58, 125.78 (dd, J ) 268, 253 Hz), 127.53, 136.72, 150.05,
158.13; 19F-NMR (CDCl3) -94.3 (dt, J ) 218, 22 Hz), -114.2
(d, J ) 218, 22 Hz); MS (CI) m/z (%) 337 (M + H+, 100). Anal.
Calcd for C13H15F2Cl2NS: C, 47.86; H, 4.63; N, 4.29. Found:
C, 47.96; H, 4.79; N, 4.06.
4-[2,2-Dich lor o-1,1-d iflu or o-2-(2-p yr id ylth io)eth yl]cy-
1
cloh exen e: 938 mg (68%); pale yellow oil; H-NMR (CDCl3)
1.62 (1H, ddd, J ) 12, 9, 4 Hz), 2.11-2.38 (4H, m), 2.38-2.55
(1H, m), 2.74-3.03 (1H, m), 5.63-5.77 (2H, m), 7.39 (1H, ddd,
J ) 7, 5, 1 Hz), 7.79 (1H, td, J ) 7, 2 Hz), 7.89 (1H, dt, J ) 7,
1 Hz), 8.71 (1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR (CDCl3) 23.07
(dd, J ) 8, 4 Hz), 25.06, 26.46 (dd, J ) 8, 4 Hz), 38.98 (t, J )
23 Hz), 94.84 (t, J ) 35 Hz), 121.88 (t, J ) 259 Hz), 122.87,
125.38, 126.89, 132.22, 137.60, 150.89, 152.07; 19F-NMR
(CDCl3) -101.5 (dd, J ) 243, 12 Hz), -105.8 (dd, J ) 243, 15
Hz); MS m/ z (%) 323 (M+, 4), 111 (100). Anal. Calcd for
C13H13Cl2F2NS: C, 48.16; H, 4.04; N, 4.32. Found: C, 48.11;
H, 4.22; N, 4.33.
P h otor ea ction of 1f a n d 3 was performed as above using
1f (499 mg, 2.0 mmol), 3 (2.0 mL, ca. 20 mmol), and CH2Cl2 (2
mL) with irradiation for 5 h.
3-[(2-P yr idylth io)m eth yl]cycloh exen e (4f): 77 mg (18%);
pale yellow oil; 1H-NMR (CDCl3) 1.26-2.03 (6H, m), 2.36-2.53
(1H, m), 3.142 (1H, dd, J ) 13, 7 Hz), 3.23 (1H, dd, J ) 13, 6
Hz), 5.68-5.81 (2H, m), 6.96 (1H, ddd, J ) 7, 5, 1 Hz), 7.18
(1H, dt, J ) 8, 1 Hz), 7.46 (1H, ddd, J ) 8, 7, 2 Hz), 8.42 (1H,
ddd, J ) 5, 2, 1 Hz).
2,2-Dich lor o-1,1-d iflu or o-3-[3,3-d iflu or o-4,4-d ich lor o-
2-m eth yl-3-(2-p yr id ylth io)bu t-2-yl]cyclop en ta n e (8c): 94
1
mg (6%); pale yellow oil; H-NMR (CDCl3) 1.62 (3H, t, J ) 2
Hz), 1.95 (3H, s), 2.07-2.52 (4H, m), 3.58-3.68 (1H, m), 7.41
(1H, ddd, J ) 7, 5, 1 Hz), 7.80 (1H, dt, J ) 7, 2 Hz), 7.88 (1H,
td, J ) 7, 1 Hz), 8.73 (1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR
(CDCl3) 21.45 (t, J ) 5 Hz), 21.65 (dd, J ) 7, 3 Hz), 23.38 (t,
J ) 4 Hz), 28.03 (dd, J ) 25, 21 Hz), 48.45 (t, J ) 22 Hz),
50.17 (t, J ) 4 Hz), 91.31 (t, J ) 25 Hz), 94.86 (t, J ) 37 Hz),
122.34 (t, J ) 268 Hz), 125.13, 125.45 (t, J ) 268 Hz), 132.80,
137.68, 150.99, 152.07; 19F-NMR (CDCl3) -92.5 (dt, J ) 220,
25 Hz), -97.1 (s), -116.6 (d, J ) 220 Hz); MS (CI) m/z (%)
458 (M + H+, 72), 460 (100). Anal. Calcd for C15H15F4Cl4NS:
C, 39.24; H, 3.29; N, 3.05. Found: C, 39.25; H, 3.43; N, 3.09.
P h otor ea ction of 1d a n d 3 was performed as above using
1d (742 mg, 3.0 mmol), 3 (3.0 mL, ca. 30 mmol), and CH2Cl2
(3 mL) with irradiation for 5 h.
3-[2,2-Dich lor o-1,1-d iflu or o-2-(2-p yr id ylth io)eth yl]cy-
cloh exen e (5f): 109 mg (16%); colorless oil; 1H-NMR (CDCl3)
1.33-1.82 (3H, m), 1.88-2.06 (3H, m), 2.25-2.71 (3H, m), 5.64
(1H, br d, J ) 10 Hz), 5.76 (1H, dtd, J ) 10, 4, 2 Hz), 7.39
(1H, ddd, J ) 7, 5, 2 Hz), 7.79 (1H, td, J ) 7, 2 Hz), 7.87 (1H,
dt, J ) 7, 1 Hz), 8.71 (1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR
(CDCl3) 21.06, 24.94, 29.63, 29.93, 38.07 (t, J ) 22 Hz), 94.75
3-Meth yl-1-(2-p yr id ylth io)-3-bu ten e (4d ): 124 mg (19%);
1
pale yellow oil; H-NMR (CDCl3) 1.79 (3H, t, J ) 1 Hz), 2.42
(20) The dichloromethylene carbon signal was not clearly identified
due to the low signal-to-noise ratio.

Cyclization of Hindered Fluorinated Alkenyl Radicals
J . Org. Chem., Vol. 62, No. 21, 1997 7199
(t, J ) 32 Hz), 122.65 (t, J ) 258 Hz), 124.93, 128.61, 130.81,
132.11, 137.64, 150.96, 152.12; 19F-NMR (CDCl3 ) -102.0 (dd,
J ) 37, 15 Hz); MS m/ z (%) 337 (M+, 6), 112 (100). Anal.
Calcd for C14H15F2Cl2NS: C, 49.71; H, 4.47; N, 4.14. Found:
C, 49.89; H, 4.42; N, 3.95.
Hz), -105.7 (d, J ) 238 Hz); MS m/ z (%) 351 (M+, 5), 111
(100). Anal. Calcd for C15H17Cl2F2NS: C, 51.14; H, 4.86; N,
3.98. Found: C, 51.04; H, 4.76; N, 4.19.
P h otor ea ction of 1h a n d 3 was performed as above using
1h (915 mg, 3.5 mmol) 3 (4.0 mL, ca. 40 mmol), and CH2Cl2 (4
mL) with irradiation for 5 h.
1-Me t h yle n e -2-[(2-p yr id ylt h io)m e t h yl]cycloh e xa n e
(4h ): 107 mg (14%); colorless oil; 1H-NMR (CDCl3) 1.25-1.76
(5H, m), 1.89-2.12 (2H, m), 2.24-2.48 (2H, m), 3.26 (1H, dd,
J ) 13, 8 Hz), 3.48 (1H, dd, J ) 13, 7 Hz), 4.71 (1H, s), 4.77
(1H, s), 6.96 (1H, ddd, J ) 7, 5, 1 Hz), 7.17 (1H, dt, J ) 8, 1
Hz), 7.46 (1H, ddd, J ) 8, 7, 2 Hz), 8.43 (1H, ddd, J ) 5, 2, 1
Hz).
(3a R*,4S*,7a R*)-3,3-Dich lor o-2,2-d iflu or o-4-(2-p yr id yl-
th io)p er h yd r oin d en e (6f): 195 mg (29%); colorless solid; mp
96-99 °C; 1H-NMR (500 MHz; CDCl3) 1.60-1.65 (2H, m),
1.70-1.75 (1H, m), 1.80-1.85 (1H, m), 1.89 (1H, ddd, J ) 15,
10, 5 Hz), 2.10 (1H, dddd, J ) 32, 15, 9, 6 Hz), 2.33 (1H, ddd,
J ) 19, 10, 5 Hz), 2.47-2.54 (1H, m), 2.56 (1H, ddd, J ) 19,
14, 10 Hz), 2.91 (1H, dt, J ) 8, 4 Hz), 4.69 (1H, q, J ) 4 Hz),
7.02 (1H, ddd, J ) 7, 5, 1 Hz), 7.21 (1H, dt, J ) 8, 1 Hz), 7.51
(1H, ddd, J ) 8, 5, 2 Hz), 8.48 (1H, ddd, J ) 5, 2, 1 Hz); 13C-
NMR (CDCl3) 20.29, 28.42, 29.39, 29.78 (d, J ) 6 Hz), 37.05
(dd, J ) 24, 20 Hz), 39.20, 52.31, 90.69 (dd, J ) 27, 24 Hz),
120.35, 123.59, 125.06 (dd, J ) 268, 252 Hz), 136.73, 149.87,
157.98; 19F-NMR (CDCl3) -115.2 (dd, J ) 221, 8 Hz), -95.2
(ddd, J ) 221, 32, 16 Hz); MS (CI) m/ z (%) 338 (M + H+, 100).
Anal. Calcd for C14H15Cl2F2NS: C, 49.71; H, 4.47; N, 4.14.
Found: C, 49.67; H, 4.33; N, 4.30.
(3a R*,4R*,7a S*)-3,3-Dich lor o-2,2-d iflu or o-4-[2,2-d ich lo-
r o-1,1-d iflu or o-2-(2-p yr id ylt h io)et h yl]p er h yd r oin d en e
(8f): 212 mg (22%); pale yellow solid; mp 70-78 °C; 1H-NMR
(500 MHz, CDCl3) 1.50-1.62 (2H, m), 1.63-1.67 (1H, m),
1.89-1.93 (1H, m), 2.05-2.17 (2H, m), 2.42-2.48 (2H, m), 2.63
(1H, ddd, J ) 22, 15, 10 Hz), 3.23 (1H, dd, J ) 9, 3 Hz), 3.53
(1H, ddd, J ) 22, 16, 6 Hz), 7.40 (1H, ddd, J ) 7, 5, 2 Hz),
7.79 (1H, td, J ) 7, 2 Hz), 7.88 (1H, ddd, J ) 7, 2, 1 Hz) 8.72
(1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR (CDCl3) 20.41, 22.99 (dd,
J ) 5, 4 Hz), 30.30 (d, J ) 7 Hz), 30.61, 37.08 (t, J ) 21 Hz),
37.67 (dd, J ) 25, 20 Hz), 45.88 (d, J ) 6 Hz), 91.40 (dd, J )
26, 25 Hz), 94.22 (t, J ) 35 Hz), 122.43 (dd, J ) 266, 261 Hz),
124.94 (dd, J ) 268, 253 Hz), 125.11, 132.52, 137.68, 151.08,
151.96; 19F-NMR (CDCl3) -116.0 (dd, J ) 221, 10 Hz), -100.1
(dd, J ) 247, 21 Hz), -93.7 (ddd, J ) 221, 32, 20 Hz), -91.5
(dd, J ) 247, 15 Hz); MS (CI) m/ z (%) 472 (M + H+, 100).
Anal. Calcd for C16H15Cl4F4NS: C, 40.79; H, 3.21; N, 2.97.
Found: C, 40.83; H, 3.30; N, 2.83.
1-Meth ylen e-2-[2,2-diflu or o-3,3-dich lor o-3-(2-pyr idylth -
1
io)p r op yl]cycloh exa n e (5h ): 87 mg (7%); colorless oil; H-
NMR (CDCl3) 1.33-1.80 (5H, m), 1.87-1.99 (1H, m), 2.04-
2.17 (1H, m), 2.24-2.35 (1H, m), 2.35-2.56 (1H, m), 2.61-
2.68 (1H, m), 2.70-2.96 (1H, m), 4.67 (1H, s), 4.72 (1H, s), 7.39
(1H, ddd, J ) 8, 4, 1 Hz), 7.79 (1H, td, J ) 7, 2Hz), 7.88 (1H,
d, J ) 8 Hz), 8.71 (1H, d, J ) 4 Hz); 13C-NMR (CDCl2) 24.20,
28.60, 34.35 (t, J ) 23 Hz), 34.45 (d, J ) 2 Hz), 34.98, 37.39
(d, J ) 2 Hz), 94.95 (t, J ) 33Hz), 106.66, 122.72 (t, J ) 258
Hz), 124.95, 132.16, 137.65, 150.99, 151.78, 152.16; 19F-NMR
(CDCl3) -100.6 (ddd, J ) 236, 30, 12 Hz), -104.1 (ddd, J )
236, 25, 10 Hz); MS (CI) m/ z (%) 352 (M + H+, 100). Anal.
Calcd for C15H17Cl2F2NS; C, 51.14; H, 4.86; N, 3.98. Found:
C, 50.92; H, 4.85; N, 3.93.
cis-3,3-Dich lor o-2,2-d iflu or o-4a -(2-p yr id ylth io)d eca h y-
d r on a p h th a len e (7h ): 631 mg (52%); colorless solid; mp 94-
96 °C; 1H-NMR (500 MHz, CDCl3) 1.33 (1H, tt, J ) 13, 3 Hz),
1.36-1.40 (1H, m), 1.54-1.62 (2H, m), 1.86-1.89 (1H, m), 1.92
(1H, tt, J ) 13, 3 Hz), 2.00 (1H, ddd, J ) 18, 7, 4 Hz), 2.23
(1H, tq, J ) 13, 2 Hz), 2.58-2.65 (2H, m), 2.70 (1H, dt, J )
33, 14 Hz), 3.32 (1H, dd, J ) 15, 5 Hz), 3.58 (1H, dd, J ) 15,
2 Hz), 7.10 (1H, ddd, J ) 7, 4, 1 Hz), 7.30 (1H, d, J ) 7 Hz),
7.54 (1H, td, J ) 7, 2 Hz), 8.52 (1H, dd, J ) 4, 1 Hz); 13C-NMR
(CDCl3) 20.24, 22.129, 26.45, 29.57, 32.62 (dd, J ) 23, 21 Hz),
32.64 (d, J ) 2 Hz), 54.52, 55.82, 85.81 (dd, J ) 29, 24 Hz),
119.49 (dd, J ) 256, 247 Hz), 121.58, 127.48, 136.82, 150.22,
157.35; 19F-NMR (CDCl3) -102.6 (ddd, J ) 236, 32, 8 Hz),
-107.4 (d, J ) 236 Hz); MS (CI) m/ z (%) 352 (M + H+, 100).
Anal. Calcd for C15H17Cl2F2NS; C, 51.14; H, 4.86; N, 3.98.
Found: C, 51.13; H, 4.96; N, 4.01.
P h otor ea ction of 1g a n d 3 was performed as above using
1g (790 mg, 3.0 mmol), which contains 5% of cyclohexylidene
isomer 10, 3 (3.0 mL, ca. 30 mmol), and CH2Cl2 (3 mL) with
irradiation for 5 h.
P h otor ea ction of 2 a n d 3 was performed as above using
2 (592 mg, 2.65 mmol), 3 (2.5 mL, ca. 25 mmol), and CH2Cl2
(2.5 mL) with irradiation for 3 h.
1-[2-(2-P yr id ylt h io)et h yl]cycloh exen e (4g): 152 mg
(23%); pale yellow oil; 1H-NMR (CDCl3) 1.50-1.68 (4H, m),
1.96-2.02 (4H, m), 2.33 (2H, t, J ) 7.6 Hz), 3.21-3.29 (2H,
m), 5.51 (1H, m), 6.96 (1H, ddd, J ) 7, 5, 1 Hz), 7.17 (1H, dt,
J ) 8, 1 Hz), 7.46 (1H, dt, J ) 8, 7, 2 Hz), 8.426 (1H, ddd, J )
5, 2, 1 Hz).
2:1 Mixt u r e of 1-[4,4-d ich lor o-3,3-d iflu or o-4-(2-p y-
r id ylth io)bu tyl]cycloh exen e (5g) a n d [4,4-d ich lor o-3,3-
d iflu or o4-(2-p yr id ylt h io)b u t ylid en e]cycloh exa n e:13 84
mg (8%: 5g; 5%); pale yellow oil; 1H-NMR (CDCl3) 1.53-1.70
(5.33H, m), 1.91-2.04 (2.67H, m), 2.16-2.29 (2.67H, m), 2.42-
2.68 (1.33H, m), 3.20 (0.67H, td, J ) 18, 7 Hz), 5.20 (0.33H,
tt, J ) 7, 1 Hz), 5.50 (0.67H, m), 7.35-7.43 (1H, m), 7.74-
7.83 (1H, m), 7.88 (1H, dt, J ) 7, 1 Hz), 8.69-8.73 (1H, m);
19F-NMR (CDCl3) -104.5 (t, J ) 19 Hz, 0.67F), -102.9 (t, J )
18 Hz; 0.33F); GC-MS m/ z (%) 5g; 351 (M+, 5),111 (100). Anal.
Calcd for C15H17Cl2F2NS: C, 51.14; H, 4.86; N, 3.98. Found:
C, 51.21; H, 4.68; N, 4.28.
1,1-Dich lor o-2,2-d iflu or o-4a -(2-p yr id ylt h io)d e ca h y-
d r on a p h th a len e (7g): 569 mg (54%); colorless solid; mp 76-
98 °C; 1H-NMR (500 MHz, CDCl3) 1.161 (1H, ddd, J ) 14, 13,
4 Hz), 1.36-1.45 (2H, m), 1.64 (2H, t, J ) 18 Hz), 1.91-2.03
(2H, m), 2.11-2.21 (2H, m), 2.26 (2H, br d, J ) 25 Hz), 3.01
(1H, dd, J ) 7, 4 Hz), 3.04-3.06 (1H, m), 7.10 (1H, ddd, J )
8, 5, 1 Hz), 7.40 (1H, d, J ) 8 Hz), 7.53 (1H, td, J ) 8, 2 Hz),
8.48 (1H, dd, J ) 5, 1 Hz); recognizable minor peaks of the
stereoisomer, 3.07 (ddd, J ) 8, 4, 1 Hz), 3.13 (dd, J ) 16, 4
Hz), 7.32 (d, J ) 8 Hz), 8.51 (dd, J ) 5, 1 Hz); 13C-NMR (CDCl3)
21.28, 22.73, 25.94, 27.83 (dd, J ) 24, 22 Hz), 34.39 (d, J ) 9
Hz), 57.87, 58.54, 90.85 (d, J ) 29, 23 Hz), 119.72 (d, J ) 258,
246 Hz), 121.95, 129.00, 136.99, 150.01, 156.93; recognizable
minor peaks of the stereoisomer, 21.05, 38.07, 56.31, 122.28,
128.47, 150.20; 19F-NMR (CDCl3) -100.6 (ddd, J ) 238, 32, 7
4-(2-P yr id ylth io)-1-p en ten e (14): 34 mg (7%); colorless
1
oil; H-NMR (CDCl3) 1.82 (2H, quintet, J ) 7 Hz); 2.15-2.28
(2H, m), 3.19 (2H, t, J ) 7 Hz), 4.96-5.12 (2H, m), 5.83 (1H,
ddt, J ) 17, 10, 7Hz), 6.97 (1H, ddd, J ) 7, 5, 1 Hz), 7.18 (1H,
dt, J ) 8, 1 Hz), 7.48 (1H, ddd, J ) 8, 7, 2 Hz), 8.43 (1H, ddd,
J ) 5, 2, 1 Hz).
6,6-Dich lor o-5,5-d iflu or o-6-(2-p yr id ylt h io)-1-h ep t en e
(15): colorless oil; 408 mg (49%); 1H-NMR (CDCl3) 1.71-1.83
(2H, m), 2.32-2.60 (2H, m), 4.99-5.13 (2H, m), 5.12 (2H, br
q, J ) 7 Hz), 5.82 (1H, ddt, J ) 17, 10, 7 Hz), 7.39 (1H, ddd,
J ) 8, 5, 1 Hz), 7.79 (1H, td, J ) 8, 2 Hz), 7.88 (1H, ddd, J )
8, 1, 1 Hz), 8.705 (1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR (CDCl3)
20.85 (t, J ) 3 Hz), 31.52 (t, J ) 24 Hz), 33.10, 94.58 (t, J )
33 Hz), 115.95, 122.45 (t, J ) 256 Hz), 124.94, 137.64, 137.87,
150.97, 152.11; 19F-NMR (CDCl3) -103.9 (t, J ) 19 Hz); MS
(CI) 312 (M + H+, 100). Anal. Calcd for C12H13Cl2F2NS: C,
46.17; H, 4.20; N, 4.49. Found: C, 46.27; H, 4.20; N, 4.38.
2,2-Dich lor o-1,1-d iflu or o-3-[(2-p yr id ylth io)m eth yl]cy-
cloh exa n e (16): 122mg (15%); colorless oil; 1H-NMR (CDCl3)
1.36-1.85 (3H, m), 2.07-2.58 (4H, m) 3.141 (1H, dd, J ) 14,
10, 1 Hz), 4.02 (1H, dd, J ) 14, 3, 1 Hz), 7.00 (1H, ddd, J ) 7,
5, 1 Hz), 7.21 (1H, dt, J ) 8, 1 Hz), 7.50 (1H, ddd, J ) 8, 7, 2
Hz), 8.45 (1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR (CDCl3) 20.13
(dd, J ) 7, 3 Hz), 26.90, 30.58 (t, J ) 22 Hz), 30.71, 49.80,
92.69 (dd, J ) 28, 24 Hz), 120.04 (dd, J ) 264, 245 Hz), 120.03,
122.32, 136.47, 149.99, 158.49; 19F-NMR (CDCl3) -105.0 (m);
MS m/z (%) 311 (M+, 100). Anal. Calcd for C12H13Cl2F2NS:
C, 46.17; H, 4.20; N, 4.49. Found: C, 46.45; H, 4.43; N, 4.44.
2,2-Dich lor o-1,1-d iflu or o-3-[3,3-d ich lor o-2,2-d iflu or o-
3-(2-p yr id ylth io)p r op yl]cycloh exa n e (17): 168 mg (18%);

7200 J . Org. Chem., Vol. 62, No. 21, 1997
Okano et al.
1
colorless oil; H-NMR (CDCl3) 1.49-1.88 (3H, m), 2.03-2.74
30 Hz), 127.81, 136.86, 140.89 (t, J ) 6 Hz), 150.27, 156.74;
19F-NMR (CDCl3) -92.8 to -93.8 (m); MS m/z (%) 315 (M+,
17), 111 (100). Anal. Calcd for C15H16ClF2NS: C, 57.05; H,
5.11; N, 4.44. Found: C, 57.37; H, 5.19; N, 4.20.
(5H, m), 3.11-3.39 (1H, m), 7.410 (1H, ddd, J ) 8, 5, 2 Hz),
7.80 (1H, td, J ) 8, 2 Hz), 7.88 (1H, ddd, J ) 8, 2, 1 Hz), 8.71
(1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR (CDCl3) 20.16 (d, J ) 9
Hz), 28.98 (d, J ) 4Hz), 30.39 (dd, J ) 24, 21 Hz), 34.02 (td,
J ) 21, 2 Hz), 44.71, 92.63 (dd, J ) 29, 23 Hz), 94.13 (t, J )
32 Hz), 119.72 (dd, J ) 257, 248 Hz), 122.23 (t, J ) 258 Hz),
125.17, 132.34, 137.76, 151.05; 19F-NMR (CDCl3) -100.8 to
-102.6 (m), -103.8 to -105.5 (m); MS m/ z (%) 443 (M+, 6),
78 (100). Anal. Calcd for C14H13Cl4F4NS: C, 37.78; H 2.94;
N, 3.15. Found: C, 37.80; H, 2.95; N, 3.13.
1-Ch lor o-2,2-d iflu or o-4a -(2-p yr id ylth io)-2,3,4,4a ,5,6,7,8-
octa h yd r on a p h th a len e (22). A mixture of 7g (829 mg, 2.35
mmol), Na2S‚9H2O (565 mg, 2.53 mmol), and KOH (85%, 132
mg, 2.00 mmol) dissolved in 95% aqueous EtOH (6 mL) was
refluxed for 5 h. Then, the solvents were removed under the
reduced pressure. The resulting mixture was chromato-
graphed on a SiO2 column eluting with hexane-CH2Cl2 (1:
1.5) to give 14 as pale yellow oil: 620 mg (83%); 1H-NMR
(CDCl3) 1.24-1.61 (3H, m), 1.80 (1H, tdd, J ) 14, 3, 2 Hz),
1.89-2.01 (1H, m), 2.07 (1H, tt, J ) 13, 4 Hz), 2.17-2.43 (3H,
m), 2.72 (1H, dddd, J ) 32, 14, 10, 3 Hz), 2.70-2.92 (1H, m),
2.99 (1H, ddt, J ) 15, 4, 2 Hz), 7.14 (1H, ddd, J ) 8, 5, 1 Hz),
7.37 (1H, dt, J ) 8, 1 Hz), 7.57 (1H, ddd, J ) 8, 8, 2 Hz), 8.51
(1H, ddd, J ) 5, 2, 1 Hz); 13C-NMR (CDCl3) 21.35, 25.90, 27.31,
29.88 (t, J ) 24 Hz), 32.41 (d, J ) 8 Hz), 38.03, 57.48, 117.08
(t, J ) 237 Hz), 122.17, 124.95 (t, J ) 28 Hz), 128.54, 144.60
(dd, J ) 7, 5 Hz), 150.39, 156.87; 19F-NMR (CDCl3) -90.0 (ddd,
J ) 252, 32, 17 Hz), -95.4 (d, J ) 252 Hz); MS m/z (%) 315
(M+, 27), 111 (100). Anal. Calcd for C15H16ClF2NS: C, 57.05;
H, 5.11; N, 4.44. Found: C, 57.22; H, 4.94; N, 4.45.
2,2-Diflu or o-1,2,3,4,5,6,7,8-oct a h yd r on a p h t h a le n -1-
on e (23). To a stirred solution of 22 (316 mg, 1.00 mmol) in
CH2Cl2 (20 mL) was added a solution of m-CPBA (70%, 320
mg, 1.30 mmol) in CH2Cl2 (20 mL) in 5 min at -78 °C under
N2 atmosphere. The mixture was stirred at -78 °C for 8 h,
and then (CH3)2S (0.5 mL) was added. The mixture was
allowed to warm up to room temperature, washed with
saturated aqueous NaHCO3 solution, and dried over Na2SO4.
The solvent was removed under reduced pressure and the
residue was chromatographed on a SiO2 column eluting with
hexane-EtOAc (5:1) to give 17 as colorless oil: 160 mg (86%);
1H-NMR (CDCl3) 1.62-1.69 (4H, m), 2.20-2.30 (4H, m), 2.31-
2.44 (2H, m), 2.45-2.54 (2H, m); 13C-NMR (CDCl3) 21.39,
21.65, 21.98, 28.21 (t, J ) 5 Hz), 31.48 (t, J ) 23 Hz), 31.90,
113.46 (t, J ) 247 Hz), 131.43, 159.47, 185.95 (t, J ) 25 Hz);
19F-NMR (CDCl3) -107.7 (ddd, J ) 268, 32, 12 Hz), -114.1
(ddd, J ) 268, 12, 7 Hz); IR (neat film) 1694, 1630 cm-1; MS
m/z (%) 186 (M+, 94), 122 (100). Anal. Calcd for C10H12F2O:
C, 64.51; H, 6.50. Found: C, 64.72; H, 6.27.
3,3-Diflu or o-2,3,4,4a ,5,6,7,8-oct a h yd r on a p h t h a len -2-
on e (27) was obtained in a manner similar to that for 23 from
26 (317 mg, 1.00 mmol), m-CPBA (70%, 320 mg, 1.3 mmol),
and CH2Cl2 (40 mL): 132 mg (79%); colorless oil; 1H-NMR
(CDCl3) 1.20-1.65 (3H, m), 1.84-2.17 (3H, m), 2.27 (1H, td, J
) 13, 5 Hz), 2.47-2.73 (3H, m), 5.95 (1H, dd, J ) 4, 2 Hz);
13C-NMR (CDCl3) 25.07, 26.81, 34.60, 35.64, 36.74 (dd, J ) 7,
2 Hz), 37.88 (dd, J ) 23, 21 Hz), 113.41 (dd, J ) 250, 244 Hz),
121.93, 170.51, 186.39 (t, J ) 25 Hz); 19F-NMR (CDCl3) -107.6
(ddd, J ) 268, 32, 12 Hz), -114.0 (ddd, J ) 268, 12, 7 Hz); MS
m/z (%) 186 (M+, 91), 122 (100). Anal. Calcd for C10H12F2O:
C; 64.51; H, 6.50. Found: C, 64.41; H, 6.60.
X-r a y Str u ctu r e Deter m in a tion of 8f, 7g, a n d 7h .
Colorless crystals of 8f, 7g, and 7h were obtained by layering
concentrated solutions in benzene. The crystal of 7g was
identical with the major product of 7g, which was confirmed
by the 1H NMR spectrum. All measurements were made on
a Rigaku diffractometer (AFC5R) with Mo KR radiation. Each
cell constant and orientation matrix for data collection were
obtained from least squares refinement using the setting of
25 reflections in the each given range as below, and the
individual crystallographic data are as follows. The data were
collected at 23 °C using the ω-2θ scan technique (2θ < 55.0°).
Scans of (A + 0.30 tan θ)° (A ) 1.31 for 8f and 7h , A ) 1.89
for trans-7g) were made at a speed of 32.0°/min. The intensi-
ties of three representative reflections which were measured
after every 150 reflections, and no crystal decay was noticed.
The structure was solved by direct methods. The non-
hydrogen atoms were refined anisotropically. The final least-
squares refinement was based on the number of observed
reflections with [I > 3.0σ(I)]. All calculations were performed
using the TEXSAN crystallographic software package (1985).
Su m m a r y of Cr ysta l Da ta . 8f:21 setting angle, 29.63 <
2θ < 29.94°; monoclinic cell; dimensions, a ) 9.053(2) Å, b )
11.292(1) Å, c ) 18.624(1) Å, â ) 90.337(8)°; Z ) 4; V )
1903.8(1) Å3; space group, P21/n; Dcalcd ) 1.644 g/cm3; empirical
formula C16H15Cl4F4NS; number of unique reflections ) 4596
(Rint ) 0.016); number of observations ) 3323; R ) 0.031; Rw
) 0.041.
7g:21 setting angle, 8.56 < 2θ < 17.20°; triclinic cell;
dimensions, a ) 10.234(7) Å, b ) 10.992(9) Å, c ) 7.435(3) Å,
R ) 102.91(6)°, â ) 94.81(6)°, γ ) 72.96(6)°; Z ) 2; V ) 779
(1) Å3; space group, P1; Dcalcd ) 1.501 g/cm3; empirical formula
C15H17Cl2F2NS; number of unique reflections ) 3573 (Rint ) 0
.014); number of observations ) 2599; R ) 0.045; Rw ) 0.058.
7h :21 setting angle, 27.26 < 2θ < 29.58°; monoclinic cell;
dimensions, a ) 7.786(2) Å, b ) 12.882(2) Å, c ) 15.897(2) Å,
â ) 102.63(2)°; Z ) 4; V ) 1555.9 (5) Å3; space group, P21/c;
Dcalcd ) 1.504 g/cm3; empirical formula C15H17Cl2F2NS; number
of unique reflections ) 3738 (Rint ) 0 .027); number of
observations ) 2924; R ) 0.048; Rw ) 0.064.
3-Ch lor o-2,2-diflu or o-4a-(2-pyr idylth io)-1,2,4a,5,6,7,8,8a-
octa h yd r on a p h th a len e (26). A mixture of 7h (1.41 g, 4.00
mmol) and t-BuOK (628 mg, 5.60 mmol) dissolved in anhy-
drous THF (50 mL) was stirred under refluxing for 2 h. The
solvent was removed under reduced pressure. The residue was
extracted with Et2O (20 mL × 3), and the combined extracts
were washed with saturated aqueous NaCl (20 mL) and dried
over Na2SO4. The solvent was removed under reduced pres-
sure, and the residue was chromatographed by eluting with
hexane-CH2Cl2 (2:1) to give pure 26 as pale yellow oil: 1.15
Ack n ow led gm en t. This work was supported in part
by a Grant-in-Aid for Development of Scientific Re-
search from the Ministry of Education, Science, Sports,
and Culture, J apan (07555285).
1
g (90%); H-NMR (CDCl3) 1.38-1.59 (4H, m), 1.63-1.79 (2H,
m), 1.85-1.94 (1H, m), 1.97-2.13 (2H, m), 2.34 (1H, ddd, J )
28.8, 14, 10 Hz), 2.42-2.63 (2H, m), 6.57 (1H, t, J ) 2 Hz),
7.13 (1H, ddd, J ) 8, 5, 1 Hz), 7.32 (1H, dt, J ) 8, 1 Hz), 7.56
(1H, ddd, J ) 8, 8, 2 Hz), 8.51 (1H, ddd, J ) 5, 2, 1 Hz); 13C-
NMR (CDCl3) 22.11, 22.28, 27.17, 33.82, 35.94, 36.40 (t, J )
23 Hz), 55.88, 116.72 (t, J ) 238 Hz), 121.95, 126.55 (t, J )
J O970639U
(21) The atomic coordinates for this structure have been deposited
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.