Preparation and regioselective SN2′ reaction of novel gem-difluorinated vinyloxiranes with RLi

Article abstract of DOI:10.1021/jo049025x

A series of hitherto unknown 3,4-epoxy-1,1-difluorobutenes were prepared from the readily accessible α,β-epoxy ketones and these compounds were found to undergo regioselective S_N2′ reactions with hard RLi nucleophiles occurring at the highly positively charged terminal fluorine-possessing sp² carbon atom in quite sharp contrast to the cases of the corresponding nonfluorinated vinyloxiranes which only attained a low level of regioselectivity. Addition of HMPA substantially improved the products' olefinic stereoselectivity. Theoretical calculations were used to qualitatively explore the nature of selectivity in these reactions.

Full text of DOI:10.1021/jo049025x

P r ep a r a tion a n d Regioselective SN2′ Rea ction of Novel
gem -Diflu or in a ted Vin yloxir a n es w ith RLi
Hisanori Ueki, Takashi Chiba, Takashi Yamazaki,*,† and Tomoya Kitazume
Graduated School of Bioscience and Bioengineering, Tokyo Institute of Technology,
4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8510, J apan
tyamazak@cc.tuat.ac.jp
Received J une 10, 2004
A series of hitherto unknown 3,4-epoxy-1,1-difluorobutenes were prepared from the readily accessible
R,â-epoxy ketones and these compounds were found to undergo regioselective SN2′ reactions with
hard RLi nucleophiles occurring at the highly positively charged terminal fluorine-possessing sp2
carbon atom in quite sharp contrast to the cases of the corresponding nonfluorinated vinyloxiranes
which only attained a low level of regioselectivity. Addition of HMPA substantially improved the
products’ olefinic stereoselectivity. Theoretical calculations were used to qualitatively explore the
nature of selectivity in these reactions.
In tr od u ction
as far as we know, have not been reported thus far except
for perfluorinated 3,4-epoxybutene (Chart 1).7 Moreover,
considering the synthetic utility of vinyloxiranes as
intermediates8 for a wide variety of molecules, com-
pounds 1 are regarded as highly potent and versatile
building blocks possessing a CF2dC moiety, which, by
reaction with appropriate nucleophiles, could be readily
converted to the sp3-hybridized CF2 groups known to be
isosteric and isopolar to an oxygen atom9 especially in
Introduction of fluorine into organic compounds some-
times brings about a quite significant change toward
their chemical and physical properties due to the unique
effect of this atom,1 which is why fluorine-containing
compounds have drawn profound interest in fine chemical
and pharmaceutical fields. Despite such characteristics,
utilization of fluorinated organic materials is not always
easy because they are rare in nature2 and such remark-
able changes in properties enormously affect their reac-
tivity, which does not often allow application of various
synthetic methods developed for nonfluorinated proto-
types. For instance, fluorinated carbon atoms in gem-
difluorinated olefins have appeared to possess extra-
ordinarily high electrophilicity due to the strong elec-
tronic repulsion between lone pairs around fluorine atoms
and π-electrons while the corresponding nonfluorinated
counterparts usually show nucleophilicity.3 Therefore,
independent synthetic pathways should be developed,
and accordingly, various methods as well as building
units with fluorine have been synthesized and reported
thus far.1b,4
(4) (a) Percy, J . M. Top. Curr. Chem. 1997, 193, 131. (b) Tozer, M.
J .; Herpin, T. F. Tetrahedron 1996, 52, 8619. (c) Burton, D. J .; Yang,
Z.-Y.; Morken, P. A. Tetrahedron 1994, 50, 2993. (d) Be´gue´, J .-P.;
Bonnet-Delpon, D. Tetrahedron 1991, 47, 3207. (e) Tsuchiya, T. Adv.
Carbohydr. Chem. Biochem. 1990, 1, 661. (f) Welch, J . T. Tetrahedron
1987, 43, 3123. For chiral building blocks see: (g) Iseki, K.Tetrahedron
1998, 54, 13887. (h) Kitazume, T.; Yamazaki, T. Top. Curr. Chem.
1997, 193, 91. (i) Resnati, G. Tetrahedron 1993, 49, 9385. (j) Bravo,
P.; Resnati, G. Tetrahedron: Asymmetry 1990, 1, 661.
(5) Yamazaki, T.; Ueki, H.; Kitazume, T. Chem. Commun. 2002,
2670.
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(b) Motherwell, W. B.; Tozer, M. J .; Ross, B. C. J . Chem. Soc., Chem.
Commun. 1989, 1437. (c) Fried, J .; Kittisopikul, S.; Hallinan, E. A.
Tetrahedron Lett. 1984, 25, 4329. (d) Vinson, W. A.; Prickett, K. S.;
Spahic, B.; Oritz de Montellano, P. R. J . Org. Chem. 1983, 48, 4661.
(e) Hayashi, S.; Nakai, T.; Ishikawa, N.; Burton, D. J .; Naae, D. G.;
Kesling, H. S. Chem. Lett. 1979, 983. (f) Burton, D. J .; Naae, D. G.
Synth. Commun. 1973, 3, 197. (g) Burton, D. J .; Naae, D. G. J .
Fluorine. Chem. 1971, 1, 123.
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J P 02,040,373, Feb. 9, 1990. (b) Stockburger, L., III; Heicklen, J . J .
Am. Chem. Soc. 1971, 93, 3331. (c) Sianesi, D.; Bernardi, G. C.; Pasetti,
A. French Patent 1,499,094, October 20, 1967.
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Ed. 2000, 39, 890. (b) Olofsson, B.; Khamrai, U.; Somfai, P. Org. Lett.
2000, 2, 4087. (c) Trost, B. M.; Tang, W.; Schult, J . L. Org. Lett. 2000,
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Lett. 1995, 36, 7129. (h) Bideau, F. L.; Aubert, C.; Malacria, M.
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Org. Chem. 1994, 59, 5277. (j) Feldman, K. S.; Fisher, T. E. Tetrahedron
1989, 45, 2969.
Recently, we have established the preparation of
compounds 1,5 the terminally fluorine-substituted ana-
logues of vinyloxiranes, from easily obtained R,â-epoxy
ketones by way of the difluoro Wittig reaction,4b,6 which,
† Present address: Department of Applied Chemistry, Tokyo Uni-
versity of Agriculture and Technology, 2-24-16, Nakamachi, Koganei
184-8588, J apan.
(1) (a) Smart, B. E. J . Fluorine Chem. 2001, 109, 3. (b) Kitazume
T.; Yamazaki T. Experimental Methods in Organic Fluorine Chemistry;
Kodansya: Tokyo, J apan, 1998. (c) Schlosser, M. Angew. Chem., Int.
Ed. 1998, 110, 1496. (d) O’Hagan, D.; Rzepa, H. S. Chem. Commun.
1997, 645. (e) Howard, J . A. K.; Hoy, V. J .; O’Hagan, D.; Smith, G. T.
Tetrahedron 1996, 52, 12613. (f) Schlosser, M.; Michel, D. Tetrahedron
1996, 52, 99. (g) Banks, R. E.; Tatlow, J . C. J . Fluorine Chem. 1986,
33, 227.
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(3) Borisov, Y. A. J . Struct. Chem. 2002, 43, 734.
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5542. (b) Motherwell, W. B.; Tozer, M. J .; Ross, B. C. J . Chem. Soc.,
Chem. Commun. 1989, 1437.
10.1021/jo049025x CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/24/2004
7616
J . Org. Chem. 2004, 69, 7616-7627

Regioselective SN2′ Reaction of F2-Vinyloxiranes
CHART 1. gem -Diflu or in a ted Vin yloxir a n es
P r ep a r ed in th e P r esen t Wor k
F IGURE 1. Ab initio calculation of gem-difluorinated vinyl-
oxirane 1a and its prototype 2a .
nonfluorinated species was known to attain only a low
level of regioselectivity to yield a mixture of products.12
In this article, we would like to describe the full details
of the preparation of hitherto not synthesized gem-
difluorinated vinyloxiranes and their reactions with RLi
which will be discussed from the standpoint of semi-
empirical or ab initio computation.
Resu lts a n d Discu ssion
Taking relatively high reactivity of a terminally di-
fluorinated olefin part reported into account, difluorom-
ethylenation was planned to be carried out at the last
step of the preparation of 1, which led to the formation
of various types of starting materials 1 from a wide
variety of R,â-epoxy ketones easily obtained by many
protocols including their enantioselective pathways. For
the clarification of the scope and limitation of 1 as
building blocks, R,â-epoxy ketones 3b-i were prepared
from the corresponding ketones basically by such a
routine method as NaOH-mediated H2O2 epoxidation,
while 3j and 3k were obtained from epoxy alcohols by
way of oxidation with J ones reagent and pyridinium
dichromate (PDC), respectively, and trans-2,3-epoxy-1,3-
diphenyl-1-propanone 3l was purchased from a com-
mercial supplier. At the final stage, their carbonyl
moieties were difluoromethylenated with CF2Br2-hexa-
methylphosphorus triamide (HMPT)4b,6 in the presence
of MS 4A due to moisture sensitivity of the reaction
intermediates.13 All epoxy ketones 3b-l were smoothly
converted into the corresponding gem-difluoro vinyl-
oxiranes 1b-l in excellent yields (Table 1), and a slightly
decreased yield of 1e might stem from its inherent
volatility.
On standing at ambient temperature after chromato-
graphic purification, 1b was found to be partially decom-
posed within a few days and, from the residual mixture,
acid fluoride 4b and CF3-containing allylic alcohol 5b
were isolated as the sole isomeric product in both cases
whose stereochemistry was not clarified yet (Scheme 1).
1b probably reacted with air moisture in an SN2′ fashion
under concentrated conditions and the subsequent HF
elimination14 produced 4b, and moreover, HF thus gener-
ated was added to 1b to form 5b. Because of this inherent
the field of medicinal chemistry and thus utilized as
enzyme inhibitors.4f,10 On the basis of the ab initio
calculation11 of 1a and the corresponding nonfluorinated
counterpart 2a (Figure 1), introduction of fluorine atoms
has unambiguously demonstrated that the charge on the
fluorine-possessing carbon atom was unusually altered
from -0.425 to +0.805 (NBO (natural bond orbital)
charges). This result led to the expectation that hard
nucleophiles such as RLi would realize the smooth
addition to 1 at this specific site in a highly regioselective
manner. This was actually the case, and we have already
reported in the previous communication5 that the regio-
selective SN2′ reactions of RLi toward 1 in THF afforded
a wide range of difluorinated allylic alcohols, while the
(10) (a) Schirlin, D.; Baltzer, S.; Altenburger, J . M.; Tarnus, C.;
Remy, J . M. Tetrahedron 1996, 52, 305. (b) Nieschalk, J .; O’Hagan, D.
J . Chem. Soc., Chem. Commun. 1995, 719. (c) Burke, T. R., J r.; Smyth,
M. S.; Otaka, A.; Nomizu, M.; Roller, P. P.; Wolf, G.; Case, R.; Shoelson,
S. E. Biochemistry 1994, 33, 6490. (d) Blackburn, G. M.; J akeman, D.
L.; Ivory, A. J .; Williamson, M. P. Bioorg. Med. Chem. Lett. 1994, 4,
2573. (e) Thatcher, G. R. J .; Campbell, A. S. J . Org. Chem. 1993, 58,
2272. (f) Gelb, M. H. J . Am. Chem. Soc. 1986, 108, 3146. (g) Gelb, M.
H.; Svaren, J . P.; Abeles, R. H. Biochemistry 1985, 24, 1813. (h)
Blackburn, G. M.; Kent, D. E.; Kolkmann, F. J . Chem. Soc., Perkin
Trans. 1 1984, 1119.
(11) Computation was carried out by Gaussian W03 version 6.0 at
the B3LYP/6-31+G* level of theory. Frisch, M. J .; Trucks, G. W.;
Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J . R.;
Montgomery, J . A.; Vreven, T.; Kudin, K. N.; Burant, J . C.; Millam, J .
M.; Iyengar, S. S.; Tomasi, J .; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J .; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J . E.;
Hratchian, H. P.; Cross, J . B.; Adamo, C.; J aramillo, J .; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J .; Cammi, R.; Pomelli, C.;
Ochterski, J . W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador,
P.; Dannenberg, J . J .; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari,
K.; Foresman, J . B.; Ortiz, J . V.; Cui, Q.; Baboul, A. G.; Clifford, S.;
Cioslowski, J .; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Martin, R. L.; Fox, D. J .; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
J ohnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J . A.
Gaussian W03, version 6.0; Gaussian, Inc., Pittsburgh, PA, 2003.
(12) (a) Rose, C. B.; Taylor, S. K. J . Org. Chem. 1974, 39, 578. (b)
J ohnson, C. R.; Wilbur Herr, R. J . Am. Chem. Soc. 1970, 92, 4979.
(13) Hooz, J .; Gilani, S. S. H. Can. J . Chem. 1968, 46, 86.
(14) (a) Tellier, F.; Sauveˆtre, R. Tetrahedron Lett. 1993, 34, 5433.
(b) Elsheimer, S.; Michael, M.; Landavazo, A.; Slattery, D. K.; Weeks,
J . J . Org. Chem. 1988, 53, 6151.
J . Org. Chem, Vol. 69, No. 22, 2004 7617

Ueki et al.
TABLE 1. P r ep a r a tion of gem -d iflu or in a ted
TABLE 2. Solven t Effect for th e SN2′ Rea ction of 1b
w ith n -Bu Li
Vin yloxir a n es 1a
entry
product
time (h)
yield of 1 (%)
X
time yielda
E/Z
recoverya
(%)
1
2
3
4
5
6
7
8
9
1b
1c
1d
1e
1f
1g
1h
1i
1
6
1
1
1
1
2
2
1
1
1
94
(85)
88
75 (>99)
94
>99
93
96
99
91
entry (equiv)
solvent
(h)
(%)
ratioa
1
2
3
5.0
5.0
5.0
5.0
5.0
3.0
2.0
1.0
n-hexane
Et2O
THF
1,4-dioxane
THF
THF
24
2
2
24
24
2
38
52
52
66
42
59
63
36
66/34
60/40
72/28
53/47
81/19
73/27
73/27
74/26
23
1
0
15
10
0
4
5b
6
1j
1k
1l
7
8
THF
THF
2
2
0
41
10
11
97
Determined by 19F NMR. The reaction was conducted at -78
a
b
Yields in parentheses were determined by 19F NMR.
a
°C.
nation is considered to be the major reason we could not
obtain good material balance in all experiments exam-
ined.
SCHEME 1
It is well-known that reactivities of RLi and selectivi-
ties of the products change in the presence of hexameth-
ylphosphoric triamide (HMPA) possessing the strongly
chelating ability to metals.15,16 In our instance, the E/Z
ratio of the product was proved to be dramatically
improved to 95/5 by the addition of an excess amount of
HMPA (Table 3, entry 5). Further study clarified that
only 0.5 equiv of HMPA was suffice to achieve the same
level of E/Z ratio, while still 2.0 equiv of RLi was required
for complete consumption of 1b (entries 2-5). When the
reaction was conducted at -78 °C, the stereoisomeric
ratio was further increased (entries 3 and 9) with
thorough consumption of 1b, which was in quite sharp
contrast to the fact that only low conversion was realized
in the absence of HMPA (see Table 2, entry 5). Addition
of n-BuLi to a mixed solution of 1b and HMPA turned
out to be the method of choice, one reason being that
HMPA itself can react with RLi.17 Next, we checked the
effect of additives. Safe substitutes for HMPA like
tetramethylethylenediamine (TMEDA), 12-crown-4, 1,3-
dimethyl-2-imidazolidinone (DMI), and 1,3-dimethyl-
3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) attained
only slight to moderate improvement on the chemical
yields as well as the E/Z ratio of the products (entries
6-10).18
instability, compounds 1 are highly recommended to be
kept as a hexane solution under an argon atmosphere in
a refrigerator for a couple of days, except for 1h and 1i
which are stable enough even at ambient temperature.
1b was selected as the representative substrate for
finding out suitable reaction conditions with n-BuLi. At
first, an excess amount of n-BuLi (5 equiv) was employed
for treatment of 1b in several solvents at 0 °C. In
hexanes, the anticipated SN2′ product 6b was obtained
only in 38% yield as an inseparable E/Z mixture along
with 23% recovery of the starting material 1b, which did
not compete at all with the possible SN2 type direct
epoxide opening pathway (Table 2, entry 1). Acceleration
of this process and increase of the chemical yields were
observed for such ethereal solvents as Et2O, THF, and
1,4-dioxane. The reaction in 1,4-dioxane recorded the best
yield among solvents employed, but this solvent brought
about no olefinic stereoselectivity and rate retardation
(entry 4). THF and Et2O gave comparable yields, but the
former attained the better product E/Z ratio (entries 2
and 3), which was improved by lowering the temperature
but with longer reaction time necessary for completion
(entry 5). Then, we fixed THF as a solvent, and tried to
decrease the amount of n-BuLi (entries 6∼8). Usage of 2
equiv was eventually found to be effective for suppression
of unfavorable defluorination with an increase in the
chemical yields at the same E/Z ratio, but 1 equiv of
n-BuLi led to the partial recovery of 1b. This defluori-
Since the difluoro Wittig reagent from CF2Br2 and
HMPT furnishes HMPA as a byproduct, we tried to make
(15) (a) Yuan, S. Y. L.; Huang, Z.-Z.; Tang, Y.; Dai, L.-X. J . Org.
Chem. 2000, 65, 6257. (b) Ando, K.; Takemasa, Y.; Tomioka, K.; Koga,
K. Tetrahedron 1993, 49, 1579. (c) Binns, M. R.; Haynes, R. K.; Katsifis,
A. G.; Schober, P. A.; Vonwiller, S. C. J . Org. Chem. 1989, 54, 1960.
(d) Wolf, G.; Wu¨rthwein, E.-U. Tetrahedron Lett. 1988, 29, 3647. (e)
Ager, D. J .; East, M. B. J . Org. Chem. 1986, 51, 3983. (f) Hosomi, A.;
Araki, Y.; Sakurai, H. J . Am. Chem. Soc. 1982, 104, 2081. (g) Hirama,
M. Tetrahedron Lett. 1981, 22, 1905. (h) Wartski, L.; El Bouz, M.;
Seyden-Penne, J . Tetrahedron Lett. 1979, 1543. (i) Brown, C. A.;
Yamaichi, A. J . Chem. Soc., Chem. Commun. 1979, 100. (j) Ireland,
R. E.; Mueller, R. H.; Willard, A. K. J . Am. Chem. Soc. 1976, 98, 2868.
(k) Panek, E. J .; Rodger, T. J . J . Am. Chem. Soc. 1974, 96, 6921.
(16) 300 times stronger interaction with Li was observed for HMPA
than THF. See: Reich, H. J .; Kulicke, K. J . J . Am. Chem. Soc. 1996,
118, 273.
(17) Kaiser, E. M.; Petty, J . D.; Solter, L. E. J . Organomet. Chem.
1973, 61, C1.
7618 J . Org. Chem., Vol. 69, No. 22, 2004

Regioselective SN2′ Reaction of F2-Vinyloxiranes
TABLE 3. Effect of HMP A tow a r d th e Ster eoselectivity
of th e P r od u cts
TABLE 4. Rea ction of 1 w ith Va r iou s RLia
entry
1
R
yieldb (%)
84 (67):d 6ba 60/40 (93/7)d
n-Bu 51 (65): 6bb 73/27 (>99/<1)
sec-Bu 33:e 6bc 87/13f
E/Z ratioc
recoveryc (%)
X
yielda
(%)
E/Z
recovery
(%)
1
2
3
4
5
6
7
8
9
1b Me
0 (0)
0 (0)
0
0 (0)
0 (0)
35
36
0 (17)
9
entry
additive
HMPA
(equiv)
ratioa
1
2
0
63
76
78
66
62
62
52
66
49
44
73/27
95/5
>99/<1
95/5
0
0
0
0
0
0.5
0.5
1.0
2.0
0.5
0.5
0.5
0.5
0.5
t-Bu
Ph
52 (68): 6bd 94/6 (>99/<1)
58 (60): 6be 73/27 (98/2)
3b
4
furyl- 19: 6bf
1c Me 52: 6ca
>99/<1
63/37
5
6
7
8
95/5
TMEDA
12-crown-4
DMI
74/26
76/24
80/20
90/10
81/19
0
n-Bu 31 (27): 6cb 95/5 (65/35)
t-Bu
Ph
14
11
44
28
16: 6cd
31: 6ce
69: 6d a
>99/<1
10
86/14
0
0
9b
10
11 1d Me
63/37
DMPU
12
13
14
n-Bu 52 (62): 6d b 83/17 (>99/<1)
t-Bu
Ph
0 (0)
0
0
49: 6d d
50: 6d e
65: 6ea
97/3
77/23
Determined by 19F NMR. The reaction was conducted at -78
a
b
°C.
15 1e Me
0
16
17
18
n-Bu 63 (70): 6eb
0 (0)
0
0
20 (7)
0 (0)
9 (19)
80 (42)
0 (0)
8
t-Bu
Ph
69: 6ed
81: 6ee
use of it and found out that, by application of the
standard amount of n-BuLi (2.0 equiv) at 0 °C, the
reaction mixture of 1b without any further purification
afforded the desired SN2′ product in good yield (51%) with
the E/Z selectivity (86/14) between the cases with (95/5,
entry 2) and without HMPA (73/27, entry 1).
19 1f n-Bu
20 1g n-Bu 54 (61): 6gb 78/22 (>99/<1)
21 1h n-Bu
22 1i n-Bu 4c (12):c 6ib >99/<1 (>99/<1)
23 1j n-Bu 45 (64): 6jb 67/33 (97/3)
24 1k Ph
16:c 6d e
99/1
These results in hand, various kinds of RLi were
subjected to the above conditions in the presence or
absence of HMPA (Table 4). Without HMPA, almost all
RLi exclusively afforded the regioselective SN2′ products
with moderate to excellent E preference, and bulkier
organolithium reagents seemed to provide higher olefinic
E selectivity. On the other hand, addition of 0.5 equiv of
HMPA usually attained the excellent product E stereo-
selection and better chemical yields with the exception
that 5.0 equiv was required for the apparent change in
the case of MeLi (entry 1). When the well-known formyl
anion equivalent 1,3-dithiane was used, the HF-elimi-
nated product 7 was obtained possibly by way of the
initial formation of the SN2′ product (Scheme 2). On the
other hand, 1b was recovered by treatment with the
enolates derived from N,N-dimethylacetamide and ac-
etophenone as well as the carbanions from phenylacety-
lene and 1-octyne which gave the important information
that an appropriately higher pKa value was requisite for
nucleophilic reagents to smoothly construct new carbon-
carbon bonds.
25 1l n-Bu 79 (51): 6lb 64/36 (83/17)
0 (0)
a
In the parentheses are shown the results in the presence of
HMPA (0.5 equiv) at -78 °C. Isolated yield. c Determined by 19
NMR of a crude reaction mixture. The reaction was carried out
with 5 equiv of HMPA at 0 °C. e Diastereomeric ratio of 52/48.
f Combined E/Z ratio.
F
b
d
SCHEME 2
SCHEME 3
Entry 7 described 36% recovery of 1c when reacted
with MeLi, while still 26% of 1c remained intact even
with the double amount (4 equiv) of MeLi along with the
formation of 72% of 6ca observed by 19F NMR. This
trisubstituted material afforded the SN2′ products in
moderate yields (entries 7-10) along with the formation
(18) It is reported that the product regioselectivity by the reaction
between RLi and vinyloxiranes was affected by Lewis acidic additives,
but in our case, only sluggish results were obtained, possibly due to
the ready decomposition of 1b under such circumstance even in the
absence of RLi. See: (a) Alexakis, A.; Vrancken, E.; Mangeney, P.;
Chemla, F. J . Chem. Soc., Perkin Trans. 1 2000, 3352. (b) Alexakis,
A.; Vrancken, E.; Mangeney, P. J . Chem. Soc., Perkin Trans. 1 2000,
3354. (c) Mukerji, I.; Wayda, A.; Dabbagh, G.; Bertz, S. H. Angew.
Chem., Int. Ed. Engl. 1986, 25, 760.
of the oxirane-opened diene 9c and the tetrasubstituted
furan 10c by way of 5-endo-trig cyclization as the side
products (Scheme 3). Usually the 5-endo-trig mode is
disfavored on the basis of Baldwin’s rule;19 however, some
exceptional examples have been reported20 for gem-
J . Org. Chem, Vol. 69, No. 22, 2004 7619

Ueki et al.
SCHEME 4
SCHEME 5
Olefinic stereochemistry of the products was deter-
mined by NOE experiments of 6bd and 6d e as the
representative examples. In the former case, the peak
correlation was observed between vinylic hydrogen (R2)
and t-Bu (R) as well as allylic hydrogen (R4) and Me (R1),
and between Me (R1) and allylic hydrogen (R4) or vinylic
hydrogen (R2) for the latter major or minor isomers,
respectively. These facts unambiguously indicated the E
stereochemistry at the newly formed carbon-carbon
double bonds for the major isomers.
For the clarification of the inherent high reactivity of
the difluorinated materials 1, the corresponding non-
fluorinated prototype 12b was prepared and treated with
MeLi and n-BuLi under similar conditions (Scheme 5),
but 88% of 12b was recovered by the action of MeLi in
the absence of HMPA. On the other hand, although
addition of HMPA led to total disappearance of 12b,
unidentified products were obtained presumably as a
result of MeLi working as a base to abstract allylic
hydrogen; this assumption was based on the fact that this
difluorinated olefins presumably because, as was already
shown in Figure 1, the highly polarized sp2 carbon would
facilitate the reaction.21 A similar type of compounds 9h
and 11h (the stereochemistry of the latter was deter-
mined from the NOESY peak correlation between vinyl
H and allylic CH2 moieties but the former has not been
assigned yet) were also isolated when 1h was used as a
substrate. They were formed by the proton abstraction
from the benzylic position, followed by the oxirane ring-
opening sequence with and without the addition-
elimination procedure of n-BuLi, respectively (Scheme 4).
Poor conversion was recorded for the different type of
trisubstituted substrate 1i (entry 22). Stereoisomeric 1d
and 1k exhibited remarkable a difference on the product
preference (entries 14 and 24): 1d with the E oxirane
structure underwent the selective SN2′ reaction showing
the apparent effect of HMPA, while only sluggish results
were obtained from the latter Z isomer and the desired
products were formed and isolated only in the case of
PhLi. Investigation of 1f and 1g containing electron-
withdrawing and -donating moieties, respectively, showed
their sharp contrast in reactivity and only the latter gave
satisfactory results (entries 19 and 20). Cyclic 1e, mono-
substituted epoxide 1j, and 1l followed the desired
regioselective SN2′ process and the effect of HMPA was
similarly noticed (entries 15-18, 23, and 25), while
improvement of the E/Z ratio with a decrease of the
product yield was observed by the addition of HMPA to
1l.
1
Me peak was not observed by H NMR spectroscopy. If
such a reaction really occurred, the E/Z ratios of diflu-
orinated 6 might be determined not at the ring-opening
SN2′ step but by the protonation of the above type of
allylic anion generated by an excess amount of alkyl-
lithiums. The fact that 6bb was completely recovered
without any change of its original olefinic stereochemical
proportion in the presence of n-BuLi and HMPA led to
the conclusion that the product E/Z ratio was kinetically
determined at the stage of the epoxide-ring opening. As
shown above, we have unambiguously clarified the
significant effect of two fluorine atoms at the terminal
carbon of 1 toward the regioselective reactions with a
wide range of RLi.
On the basis of the previous literature on nonfluori-
nated vinyloxiranes,22 it has been suggested that E and
Z isomers might be afforded from s-trans and s-cis
conformers of 1, respectively. On the other hand, Table
4 demonstrated a tendency that E preference of the
products was dependent on the employed RLi and
increased in the order of MeLi < PhLi < n-BuLi < sec-
BuLi < t-BuLi, which was totally opposite to the order
of their inherent aggregation state in the same solvent
employed here.23 Thus, the lower aggregation state of RLi
was considered to be responsible for the production of E
isomers with higher selectivity and this might be one of
the reasons why a larger amount of HMPA was required
when MeLi was employed because this species is known
to constitute a tetrameric form in THF, the highest
aggregation state of all RLi tested in this study.
(19) (a) Baldwin, J . E. J . Chem. Soc., Chem. Commun. 1976, 734.
(b) Baldwin, J . E.; Cutting, J .; Dupont, W.; Kruse, L.; Silberman, L.;
Thomas, R. C. J . Chem. Soc., Chem. Commun. 1976, 736.
(20) (a) Ichikawa, J .; Wada, Y.; Fujiwara, M.; Sakoda, K. Synthesis
2002, 1917. (b) Ichikawa, J .; Fujiwara, M.; Wada, Y.; Okauchi, T.;
Minami, T. Chem. Commun. 2000, 1887. (c) Coe, P. L.; Burdon, J .;
Haslock, I. B. J . Fluorine Chem. 2000, 102, 43. (d) Wang, Z.-G.;
Hammond, G. B. J . Org. Chem. 2000, 65, 6547. (e) Volle, J .-N.;
Schlosser, M. Eur. J . Org. Chem. 2000, 823. (f) Ichikawa, J .; Wada,
Y.; Okauchi, T.; Minami, T. Chem. Commun. 1997, 1537.
(21) Yamazaki, T.; Hiraoka, S.; Sakamoto, J .; Kitazume, T. J . Phys.
Chem. A 1999, 103, 6820.
(22) (a) Zaidlewich, M.; Uzarewich, A.; Sarnowski, R. Synthesis 1979,
62. (b) Lenox, R. S.; Katzenellenbogen, J . A. J . Am. Chem. Soc. 1973,
95, 957.
(23) (a) Weiss, E. Angew. Chem., Int. Ed. Engl. 1993, 32, 1501. (b)
Bauer, W.; Winchester, W. R.; Schleyer, P. v. R. Organometallics 1987,
6, 2371.
7620 J . Org. Chem., Vol. 69, No. 22, 2004

Regioselective SN2′ Reaction of F2-Vinyloxiranes
SCHEME 6
F IGURE 2. The ground-state models of E and Z isomers.
The above discussion could be summarized that the
success of the present reactions would be governed by
the steric circumstance around the oxirane ring and then
we have calculated the ground state of the more realistic
stereoisomeric models Z- and E-1m (Figure 2) rather
than 1a .11 Although the most stable conformation of the
E-form was proved to be the s-trans type conformation
(with the C-C-CdCF2 dihedral angle of 152.5°) similar
to 1a , the perpendicular relationship between epoxy C-C
and CdC bonds (-67°) was observed for the Z isomer.
Our initial assumption was that the RLi attack would
occur for the most stable conformation of the E isomer
from the sterically unbiased re-face possibly with forma-
tion of chelation with the epoxy oxygen atom. On the
other hand, if the corresponding Z isomer also followed
a similar pattern, the reaction might not proceed readily
because the si-face attack was encumbered by the proxi-
mate methyl moiety, and moreover, the transition state
(TS) should increase the steric congestion due to partial
pyramidalization when RLi was approached from the
opposite re-face. Table 4 clearly indicated that this was
actually the case for 1h and 1j, the acyclic substrates
with the Z-epoxide structure leading only to sluggish
results. Then, we have started the detailed computation
for obtaining more explicit information on the present
reaction mechanism using the semiempirical computa-
tional methods.24
TABLE 5. Rela tive En er gies of th e Rea cta n ts, P r od u cts,
a n d Tr a n sition Sta tes
species
∆G (kcal/mol)
species
∆G (kcal/mol)
1a
0.00
17.12
-25.43
-24.07
-61.89
1a
0.00
27.74
-23.02
-20.41
-59.94
TS 1
In t 1
TS 3
P r o 1E
TS 2
In t 2
TS 4
P r o 1Z
TS 5E
TS 5Z
P r o 2E
P r o 2Z
-7.07
-7.49
-52.95
-52.94
TS 6E
TS 6Z
P r o 2E
P r o 2Z
-7.61
-7.93
-52.95
-52.94
Table 5. The transition state TS 1 with the expected
s-trans structure accepted the MeLi attack from the re-
face of 1a with chelation to the epoxy oxygen to produce
the intermediary In t 1, whose activation energy ∆G at
0 °C was calculated to be 17.12 kcal/mol as the rate
determining step of the whole process. On the other hand,
the corresponding TS leading to the Z isomer, TS 2,
possessed the perpendicular relationship between the
olefin and epoxide parts (the dihedral angle F2CdCsCs
C: -100.8°) where RLi approached from the opposite si-
face. The relatively large activation energy difference of
10.6 kcal/mol between TS 1 and TS 2 allowed us to
qualitatively anticipate exclusive E olefin formation and
this is totally consistent with the experimental results
(Table 4). First intermediates In t 1 and 2 would then
experience either the epoxide opening via TS 3 and TS
4 to the final product P r o 1E and 1Z, respectively, or
the LiF elimination (TS 5 and 6) to the monofluorinated
butadiene monooxide, P r o 2E or 2Z. Table 5 points out
the ready formation of P r o 1E and 1Z with a quite low
energy barrier of 1-3 kcal/mol rather than the other
elimination pathways (15-18 kcal/mol activation energy
We selected the simplest gem-difluorinated vinyl-
oxirane 1a as was already shown in Figure 1 and
monomeric MeLi as the representative nucleophile. Me2O
molecules as the smallest ethereal solvent were added
to the lithium atom so as to fulfill its tetracoordinated
circumstance. The result is summarized in Scheme 6 and
(24) Semiempirical molecular orbital calculation was performed by
MOPAC v 6.10 (PM3) implemented in CAChe Worksystem (Fujitsu)
for all the conformers obtained by CONFLEX with the threshold value
of 25 kcal, followed by their full optimization by the eigenvector
following the minimization (EF) method with the extra keyword
“PRECISE”, final gradient norm being less than 0.01 kcal/Å.
J . Org. Chem, Vol. 69, No. 22, 2004 7621

Ueki et al.
J ) 1.38 Hz), 7.17-7.31 (5 H, m). 19F NMR δ 68.2 (1 F, dd, J
) 45.8, 7.10 Hz), 74.8 (1 F, dd, J ) 42.4, 3.05 Hz). 13C NMR δ
6.60 (t, J ) 1.15 Hz), 32.1, 33.6, 54.0 (dd, J ) 6.53, 2.52 Hz),
55.4 (t, J ) 1.72 Hz), 83.3 (dd, J ) 20.1, 13.7 Hz), 125.9, 128.1,
128.3, 140.1, 154.8 (t, J ) 287.5 Hz). IR (neat) ν 699, 744, 790,
880, 948, 1058, 1134, 1210, 1257, 1303, 1451, 1496, 1603, 1750,
2366, 2861, 2931, 2997, 3025, 3062, 3585, 3629, 3655, 3751
was required), which supported P r o 2E and/or 2Z
produced only as minor byproducts. As the size of the R
moiety in RLi increases, the higher rotational energy was
likely to be required for the formation of the more
sterically constrained In t 2 compared with In t 1 and In t
3, which supported the E preference of the stereochemical
outcome in the current reaction. Taking these results into
account, we estimated the effect of HMPA. As was
already pointed out, the re-face attack of RLi to the
s-trans conformer gave rise to intermediate In t 1 to
eventually afford the difluorinated P r o 1E, or P r o 2E
or 2Z with one fluorine atom after RF2C-C bond rota-
tion.25 Addition of HMPA promoted the coordination to
lithium to lower the Li-C bond strength and develop
more anionic character on the lithium-bound carbon
atom. In t 2 was the energetically preferred intermediate
over In t 3 by 12.7 kcal/mol, but HMPA would diminish
the effect of the intramolecular chelation to increase the
population of In t 3 from which P r o 1E was obtained
through the epoxy ring opening by the SN2 type mecha-
nism of the carbanionic species, leading to increase of the
P r o 1E proportion as was actually observed from the
experimental results.
cm-1
.
(E)-3,4-Ep oxy-2-eth yl-1,1-d iflu or o-3-m eth yl-6-p h en yl-
1
h ex-1-en e (1c): H NMR δ 1.07 (3 H, dd, J ) 7.57, 7.44 Hz),
1.38 (3 H, s), 1.85-1.96 (2 H, m), 2.02-2.10 (2 H, m), 2.77 (1
H, m), 2.83 (1 H, m), 2.96 (1 H, t, J ) 6.35 Hz), 7.18-7.32 (5
H, m). 19F NMR δ 67.5 (1 F, d, J ) 51.4 Hz), 73.3 (1 F, d, J )
50.4 Hz). 13C NMR δ 13.5 (dd, J ) 2.87, 2.58 Hz), 17.9 (dd, J
) 2.87, 1.43 Hz), 18.0 (d, J ) 2.30 Hz), 30.5, 32.4, 58.0 (dd, J
) 6.02, 1.58 Hz), 63.1 (dd, J ) 2.58, 0.86 Hz), 93.8 (dd, J )
18.2, 13.6 Hz), 126.0, 128.2, 128.3, 141.0 153.4 (dd, J ) 287.4,
287.2 Hz). IR (neat) ν 699, 746, 793, 826, 865, 904, 960, 995,
1066, 1091, 1137, 1237, 1263, 1311, 1380, 1456, 1496, 1604,
1743, 2874, 2935, 2972, 3028, 3063 cm-1
.
(E )-3,4-E p oxy-1,1-d iflu or o-2-m e t h yl-4-p h e n ylb u t -1-
en e (1d ): 1H NMR δ 1.55 (3 H, dd, J ) 3.29, 3.03 Hz), 3.63 (1
H, q, J ) 1.65 Hz), 3.88 (1 H, d, J ) 1.92 Hz), 7.25-7.40 (5 H,
m). 19F NMR δ 68.9 (1 F, dqd, J ) 44.8, 3.45, 1.72 Hz), 75.5 (1
F, m). 13C NMR δ 6.35 (dd, J ) 1.43, 1.14 Hz), 55.8 (t, J )
1.72 Hz), 57.9 (dd, J ) 6.30, 2.58 Hz), 83.4 (dd, J ) 20.5, 13.9
Hz), 125.3, 128.1, 128.3, 136.4, 155.1 (dd, J ) 288.4, 287.6 Hz).
IR (neat) ν 696, 741, 802, 846, 873, 1086, 1125, 1187, 1226,
Con clu sion s
1254, 1300, 1458, 1499, 1750, 2338,2361, 2932, 3001 cm-1
.
In summary, we have successfully established the
novel synthetic route to the hitherto unprecedented gem-
difluorinated vinyloxiranes which would be regarded as
highly potential synthetic intermediates for the construc-
tion of a wide variety of fluorine-possessing compounds
starting from various kinds of R,â-epoxy ketones by way
of the difluoro Wittig reaction. Their reactions with RLi
enabled the highly regioselective SN2′ type oxirane-
opening process due to the extraordinary electrophilic sp2
carbon atom by the significant p-π electronic repulsive
effect of fluorine to furnish difluorinated allylic alcohols
with good to excellent E stereoselectivity, which was
greatly improved by the addition of only 0.5 equiv of
HMPA. At present, reactions of these gem-difluorinated
vinyloxiranes with other nucleophilic species are under-
way in this laboratory.
2,3-Ep oxy-1-d iflu or om eth ylid en e-3,5,5-tr im eth ylcyclo-
h exa n e (1e): 1H NMR δ 0.85 (3 H, s), 0.95 (3 H, s), 1.37 (3 H,
s), 1.54 (1 H, d, J ) 15.1 Hz), 1.75 (1 H, dd, J ) 15.0, 0.69 Hz),
1.81 (2 H, m), 3.52 (1 H, t, J ) 1.51 Hz). 19F NMR δ 66.9 (1 F,
dd, J ) 48.0, 2.75 Hz), 73.6 (1 F, dq, J ) 48.0, 2.58 Hz). 13C
NMR δ 24.8, 26.9, 29.8 (dd, J ) 2.01, 0.86 Hz), 30.1 (d, J )
0.86 Hz), 31.4 (d, J ) 0.86 Hz), 43.2, 55.3 (dd, J ) 7.16, 2.00
Hz), 58.2 (dd, J ) 1.72, 0.86 Hz), 84.9 (dd, J ) 20.9, 13.5 Hz),
155.2 (dd, J ) 288.6, 286.3 Hz). IR (neat) ν 815, 907, 933, 1000,
1055, 1098, 1173, 1226, 1297, 1373, 1415, 1457, 1751, 1798,
2872, 2958 cm-1
.
(E)-3,4-Ep oxy-1,1-d iflu or o-2-m eth yl-4-(4-n itr op h en yl)-
bu t-1-en e (1f): 1H NMR δ 1.57 (3 H, dd, J ) 3.29, 3.04 Hz),
3.62 (1 H, q, J ) 1.65 Hz), 4.00 (1 H, d, J ) 1.92 Hz), 7.44-
7.53 (2 H, m), 8.19-8.27 (2 H, m). 19F NMR δ 69.9 (1 F, dqd,
J ) 43.5, 3.44, 1.71 Hz), 76.7 (1 F, m). 13C NMR δ 6.58 (dd, J
) 1.72, 1.15 Hz), 55.1 (m), 58.8 (dd, J ) 6.58, 2.29 Hz), 83.0
(dd, J ) 21.3, 13.6 Hz), 123.7, 126.2, 143.9, 147.8, 155.5 (t, J
) 288.9 Hz). IR (KBr) ν 528, 586, 607, 690, 741, 771, 806, 830,
848, 864, 891, 976, 1012, 1085, 1121, 1183, 1224, 1253, 1302,
1345, 1458, 1522, 1602, 1686, 1749, 1937, 3116 cm-1. Anal.
Calcd for C11H9F2NO3: C, 54.78; H, 3.76; N, 5.81. Found: C,
54.75; H, 4.16; N, 5.55. Mp 69 °C.
(E)-3,4-Epoxy-1,1-diflu or o-2-m eth yl-4-(4-m eth ylph en yl)-
bu t-1-en e (1g): 1H NMR δ 1.53 (3 H, dd, J ) 3.29, 3.02 Hz),
2.34 (3 H, s), 3.61 (1 H, dd, J ) 3.29, 1.93 Hz), 3.84 (1 H, d, J
) 1.92 Hz), 7.17 (4 H, bs). 19F NMR δ 68.8 (1 F, ddd, J ) 45.0,
8.39, 3.05 Hz), 75.3 (1 F, dq, J ) 45.0, 3.05 Hz). 13C NMR δ
6.63 (dd, J ) 1.15, 1.14 Hz), 21.3, 55.9 (dd, J ) 1.72, 1.71 Hz),
58.0 (dd, J ) 6.30, 2.57 Hz), 83.4 (dd, J ) 20.3, 14.0 Hz), 125.4,
129.1, 133.4, 138.1, 155.2 (t, J ) 288.0 Hz). IR (KBr) ν 351,
382, 409, 501, 536, 563, 586, 609, 752, 795, 822, 872, 972, 1088,
1103, 1130, 1184, 1227, 1258, 1300, 1346, 1381, 1447, 1520,
1616, 1748, 1913, 2099, 2257, 2874, 2928, 3036 cm-1. Mp 37
°C.
Exp er im en ta l Section
Gen er a l P r oced u r e for Diflu or in a ted Vin yloxir a n es
1. To a flask containing ca. 200 mg of MS 4 Å were added 10
mL of dry THF and dibromodifluoromethane (0.46 mL, 5.0
mmol) at -78 °C under argon. After formation of a white
precipitate by further addition of hexamethylphosphorus tria-
mide (1.82 mL, 10.0 mmol), the mixture was allowed to warm
to room temperature. Then, a starting epoxy ketone (2.0 mmol)
was added with 4 mL of dry THF and the mixture was, after
1 h, filtered under reduced pressure with the aid of n-hexane.
Saturated sodium hydrogen carbonate was added to the
filtrate, the organic layer was extracted with n-hexane three
times, and the combined organic layer was dried over anhy-
drous MgSO4. After evaporation of the solvents, purifica-
tion by short-path Florisil column chromatography (n-hex-
ane:AcOEt ) 60:1) afforded the desired terminally difluori-
nated vinyloxirane 1 in excellent yield as shown in Table 1.
(E )-3,4-E p oxy-1,1-d iflu or o-2-m e t h yl-6-p h e n ylh e x-1-
en e (1b): 1H NMR δ 1.39 (3 H, m), 1.88-1.93 (2 H, m), 2.72-
2.86 (2 H, m), 2.98 (1 H, td, J ) 5.86, 2.45 Hz), 3.34 (1 H, q,
2-Be n zyl-3,4-e p oxy-1,1-d iflu or o-2-m e t h ylb u t -1-e n e
(1h ): 1H NMR δ 1.54 (3 H, dd, J ) 3.30, 3.02 Hz), 2.82 (1 H,
d, J ) 4.94 Hz), 2.85 (1 H, ddd, J ) 4.94, 1.64, 0.54 Hz), 2.91
(1 H, d, J ) 14.3 Hz), 3.04 (1 H, d, J ) 14.3 Hz), 7.17-7.34 (5
H, m). 19F NMR δ 68.6 (1 F, dq, J ) 47.0, 3.01 Hz), 74.4 (1 F,
ddq, J ) 47.0, 5.17, 3.01 Hz). 13C NMR δ 9.59 (dd, J ) 2.00,
0.86 Hz), 40.8 (dd, J ) 2.86, 1.43 Hz), 53.3 (dd, J ) 3.14, 0.57
Hz), 57.5 (dd, J ) 7.16, 2.58 Hz), 85.5 (dd, J ) 20.6, 16.9 Hz),
(25) Lee, J .; Tsukazaki, M.; Snieckus, V. Tetrahedron Lett. 1993,
34, 415.
7622 J . Org. Chem., Vol. 69, No. 22, 2004

Regioselective SN2′ Reaction of F2-Vinyloxiranes
126.8, 128.2, 129.5, 135.7, 153.6 (dd, J ) 287.2, 285.7 Hz). IR
(neat) ν 673, 701, 752, 780, 825, 859, 898, 941, 976, 1031, 1091,
1137, 1186, 1249, 1284, 1388, 1455, 1496, 1605, 1751, 1949,
2346, 2365, 2929, 2996, 3031, 3064, 3087 cm-1. Anal. Calcd
for C12H12F2O: C, 68.56; H, 5.75. Found: C, 68.10; H, 6.10.
1496, 2863, 2933, 3029, 3064, 3375 cm-1. Anal. Calcd for
C
13H15F3O: C, 63.93; H, 6.19. Found: C, 63.97; H, 6.05.
Gen er a l P r oced u r e for th e Rea ction s w ith RLi a n d F 2-
Vin yloxir a n es. The reaction of (E)-3,4-epoxy-1,1-difluoro-2-
methyl-6-phenylhex-1-ene (1b) and MeLi is described as the
representative example. To a flask containing 1b (0.10 g, 0.45
mmol) and 5 mL of dry THF was added 2.0 equiv of MeLi at
0 °C under an argon atmosphere. After 2 h of stirring and an
addition of NH4Cl aq, the reaction mixture was extracted with
ether three times, and dried over anhydrous MgSO4. After
removal of solvents, purification by silica gel column chroma-
tography (n-hexane:AcOEt ) 4:1) furnished the product 6ba
in 84% yield. When HMPA is employed as an additive, 0.5 or
5.0 equiv of HMPA is introduced before the addition of MeLi.
Then, similar treatment gave the same product in 78% or 67%
yields (E:Z ) 68:32 or 93:7, respectively).
3,4-Ep oxy-1,1-d iflu or o-2-m eth yl-6-p h en yl-4-(2-p h en yl-
eth yl)h ex-1-en e (1i): 1H NMR δ 1.53 (3 H, td, J ) 4.30, 0.82
Hz), 1.57-1.99 (3 H, m), 2.16 (1 H, ddd, J ) 14.0, 9.62, 6.32
Hz), 2.65-2.86 (4 H, m), 3.30 (1 H, m), 7.13-7.35 (10 H, m).
19F NMR δ 70.9 (1 F, dddd, J ) 48.3, 8.18, 6.46, 3.45 Hz), 73.4
(1 F, dquint, J ) 48.3, 3.45 Hz). 13C NMR δ 9.87 (dd, J ) 2.29,
0.86 Hz), 31.2, 31.2, 32.7, 36.3, 59.3 (d, J ) 5.44 Hz), 63.8 (dd,
J ) 1.43, 1.43 Hz), 81.9 (dd, J ) 20.6, 15.5 Hz), 125.9, 125.9,
128.0, 128.1, 128.1, 128.3, 140.9, 141.4, 153.2 (t, J ) 286.6 Hz).
IR (neat) ν 669, 698, 747, 925, 1030, 1136, 1221, 1276, 1419,
1457, 1473, 1496, 1507, 1734, 1752, 1772, 2346, 2365, 2931,
3026 cm-1. Anal. Calcd for C21H22F2O: C, 76.81; H, 6.75.
Found: C, 76.66; H, 7.07.
6,6-Diflu or o-5-m eth yl-1-p h en ylh ep t-4-en -3-ol (6ba ): IR
(neat) ν 699, 746, 922, 1051, 1139, 1172, 1384, 1450, 1496,
1603, 1721, 2862, 2930, 3026, 3360 cm-1. Anal. Calcd for
3,4-E p oxy-1,1-d iflu or o-2-(2-p h e n yle t h yl)b u t -1-e n e
(1j): 1H NMR δ 2.06-2.13 (2 H, m), 2.59-2.82 (3 H, m), 2.90
(1 H, t, J ) 4.40 Hz), 3.58 (1 H, ddd, J ) 4.40, 2.75, 1.92 Hz),
7.14-7.33 (5 H, m). 19F NMR δ 69.9 (1 F, dq, J ) 42.7, 2.15
Hz), 76.0 (1 F, dt, J ) 42.7, 2.15 Hz). 13C NMR δ 24.1 (d, J )
1.43 Hz), 35.1 (dd, J ) 3.34, 2.48 Hz), 45.6 (t, J ) 2.00 Hz),
47.5 (dd, J ) 7.16, 2.29 Hz), 87.0 (dd, J ) 20.3, 11.5 Hz), 126.1,
128.3, 128.3, 140.8, 155.8 (dd, J ) 291.2, 288.6 Hz). IR (neat)
ν 669, 699, 736, 751, 789, 835, 870, 951, 998, 1030, 1055, 1085,
1133, 1176, 1211, 1270, 1297, 1350, 1405, 1454, 1497, 1604,
C
14H18F2O: C, 69.98; H, 7.55. Found: C, 70.39; H, 7.43. E
1
isom er : H NMR δ 1.67 (3 H, t, J ) 18.3 Hz), 1.69 (3 H, d, J
) 1.47 Hz), 1.80 (1 H, m), 1.96 (1 H, dddd, J ) 13.6, 8.40,
6.57, 6.11 Hz), 2.67 (1 H, ddd, J ) 13.8, 9.28, 6.57 Hz), 2.74 (1
H, ddd, J ) 14.0, 9.53, 5.99 Hz), 4.38 (1 H, m), 5.78 (1 H, m),
6.97-7.16 (5 H, m). 19F NMR δ 69.1 (1 F, dq, J ) 247.2, 18.3
Hz), 69.6 (1 F, dq, J ) 248.7, 18.3 Hz). 13C NMR δ 19.7 (t, J )
5.01 Hz), 22.9 (t, J ) 29.4 Hz), 31.5, 38.5, 67.3, 121.8 (t, J )
237.5 Hz), 125.8, 128.2, 130.8 (t, J ) 8.16 Hz), 133.6 (t, J )
1
1741, 2346, 2363, 2866, 2931, 3028, 3063 cm-1
.
24.6 Hz), 141.3. Z isom er : H NMR δ 1.64 (3 H, t, J ) 18.6
Hz), 1.78 (3 H, d, J ) 1.22 Hz), 1.65-1.85 (2 H, m), 2.59-2.78
(2 H, m), 4.56 (1 H, m), 5.44 (1 H, dd, J ) 9.82, 1.47 Hz), 6.97-
7.16 (5 H, m). 19F NMR δ 75.7 (1 F, dq, J ) 244.1, 18.3 Hz),
76.6 (1 F, dq, J ) 245.7, 18.3 Hz). 13C NMR δ 11.7 (t, J ) 3.15
Hz), 24.6 (t, J ) 29.4 Hz), 31.7, 38.9, 67.3, 122.6 (t, J ) 237.5
Hz), 125.7, 128.2, 133.5 (t, J ) 24.3 Hz), 134.0 (t, J ) 3.43
Hz), 141.5.
(Z)-3,4-E p oxy-1,1-d iflu or o-2-m e t h yl-4-p h e n ylb u t -1-
en e (1k ): 1H NMR δ 1.34 (3 H, td, J ) 2.38, 0.86 Hz), 3.75 (1
H, m), 4.15 (1 H, d, J ) 4.16 Hz), 7.25-7.35 (5 H, m). 19F NMR
δ 71.2 (1 F, ddt, J ) 45.8, 6.84, 3.05 Hz), 73.3 (1 F, dquint, J
) 45.8, 3.05 Hz). 13C NMR δ 9.51 (m), 55.3 (d, J ) 6.30 Hz),
57.6 (t, J ) 1.58 Hz), 81.0 (dd, J ) 22.0, 15.5 Hz), 126.0, 127.6,
127.8, 134.7, 153.8 (dd, J ) 287.6, 286.5 Hz). IR (neat) ν 605,
649, 668, 699, 728, 753, 825, 843, 894, 918, 971, 1027, 1057,
1076, 1142, 1186, 1215, 1255, 1369, 1387, 1415, 1457, 1496,
6,6-Diflu or o-5-m eth yl-1-p h en yld ec-4-en -3-ol (6bb): IR
(neat) ν 699, 740, 913, 1024, 1118, 1170, 1266, 1331, 1380,
1454, 1721, 2338, 2362, 2869, 2933, 2958, 3399 cm-1. Anal.
Calcd for C17H24F2O: C, 72.31; H, 8.57. Found: C, 72.48; H,
1757, 2342, 2360, 2960, 3033, 3065 cm-1
.
(E)-3,4-Ep oxy-1,1-d iflu or o-2,4-d ip h en ylbu t-1-en e (1l):
1H NMR δ 3.61 (1 H, d, J ) 2.20 Hz), 3.83 (1 H, dd, J ) 1.92,
1.92 Hz), 7.23-7.45 (10 H, m). 19F NMR δ 72.3 (1 F, dd, J )
31.0, 1.72 Hz), 79.5 (1 F, d, J ) 31.0 Hz). 13C NMR δ 56.9 (dd,
J ) 1.72, 1.25 Hz), 57.9 (dd, J ) 5.16, 1.15 Hz), 90.9 (dd, J )
18.0, 16.3 Hz), 125.4, 128.2, 128.3, 128.3, 128.4, 128.8 (dd, J
) 3.54, 2.39 Hz), 129.5 (dd, J ) 2.86, 2.86 Hz), 136.1, 155.9
(dd, J ) 294.6, 293.2 Hz). IR (neat) ν 696, 725, 759, 844, 875,
918, 981, 1032, 1202, 1261, 1309, 1448, 1458, 1496, 1696, 1700,
1
8.64. E isom er : H NMR δ 0.91 (3 H, t, J ) 7.14 Hz), 1.20-
1.48 (6 H, m), 1.69 (3 H, d, J ) 0.47 Hz), 1.70-2.12 (2 H, m),
2.68 (1 H, ddd, J ) 13.9, 9.15, 6.59 Hz), 2.74 (1 H, ddd, J )
13.7, 9.40, 5.98 Hz), 4.42 (1 H, m), 5.80 (1 H, dq, J ) 8.55,
1.58 Hz), 7.16-7.32 (5 H, m). 19F NMR δ 61.2 (1 F, dt, J )
231.1, 16.8 Hz), 61.8 (1 F, dt, J ) 239.6, 16.8 Hz). 13C NMR δ
12.1 (dd, J ) 3.43, 2.86 Hz), 14.0, 22.5, 24.5 (dd, J ) 4.29,
4.01 Hz), 31.5, 35.3 (dd, J ) 26.9, 26.6 Hz), 38.6 (t, J ) 1.15
Hz), 67.5, 122.9 (dd, J ) 241.3, 241.1 Hz), 125.8, 128.2, 128.3,
131.2 (dd, J ) 8.59, 8.30 Hz), 132.7 (t, J ) 23.8 Hz), 141.3. Z
isom er : 1H NMR δ 0.91 (3 H, t, J ) 7.14 Hz), 1.20-1.48 (6
H, m), 1.79 (3 H, d, J ) 1.34 Hz), 1.70-2.12 (2 H, m), 2.60-
2.82 (2 H, m), 4.53 (1 H, ddt, J ) 15.6, 7.42, 2.20 Hz), 5.54 (1
H, dq, J ) 9.15, 1.58 Hz), 7.16-7.32 (5 H, m). 19F NMR δ 61.2
(1 F, dt, J ) 244.1, 16.8 Hz), 61.8 (1 F, dt, J ) 244.1, 16.8 Hz).
13C NMR δ 12.1 (dd, J ) 3.43, 2.86 Hz), 20.2 (t, J ) 5.15 Hz),
22.5, 24.1 (dd, J ) 4.01, 3.72 Hz), 31.7, 37.1 (dd, J ) 26.9,
26.6 Hz), 39.0 (m), 67.5, 123.9 (t, J ) 242.2 Hz), 125.8, 128.2,
128.3, 133.2 (t, J ) 24.9 Hz), 134.4 (t, J ) 3.44 Hz), 141.6.
1718, 1734, 2346, 2364, 3061 cm-1
.
4-Hydor oxy-2-m eth yl-6-ph en ylh ex-2-en oyl flu or ide (4b):
1H NMR δ 1.80-1.90 (1 H, m), 1.84 (3 H, s), 2.00 (1 H, dtd, J
) 14.0, 8.24, 5.77 Hz), 2.71 (1 H, ddd, J ) 14.1, 8.24, 7.42 Hz),
2.79 (1 H, ddd, J ) 14.0, 9.04, 5.77 Hz), 4.50 (1 H, td, J )
8.24, 4.95 Hz), 6.86 (1 H, ddd, J ) 8.24, 3.02, 1.65 Hz), 7.16-
7.35 (5 H, m). 19F NMR δ 177.3 (s). 13C NMR δ 12.9 (d, J )
1.14 Hz), 31.2, 37.6, 67.8, 123.8 (d, J ) 52.4 Hz), 126.1, 128.2,
128.4, 140.6, 149.8, 158.0 (d, J ) 347.8 Hz). IR (neat) ν 698,
729, 795, 930, 957, 1030, 1069, 1169, 1215, 1315, 1389, 1454,
1497, 1605, 1651, 1802, 2342, 2365, 2862, 2932, 3028, 3063,
3372, 3530 cm-1. Anal. Calcd for C13H15FO2: C, 70.25; H, 6.80.
Found: C, 70.28; H, 7.12.
6,6,6-Tr iflu or o-5-m eth yl-1-p h en ylh ex-4-en -3-ol (5b): 1H
NMR δ 1.75 (3 H, d, J ) 1.10 Hz), 1.82 (1 H, dddd, J ) 14.5,
9.07, 6.87, 5.22 Hz), 1.98 (1 H, dddd, J ) 14.0, 8.79, 7.68, 6.32
Hz), 2.68 (1 H, ddd, J ) 14.0, 8.79, 6.87 Hz), 2.75 (1 H, ddd, J
) 14.0, 9.07, 6.32 Hz), 4.42 (1 H, m), 6.07 (1 H, dddd, J )
8.52, 3.02, 3.02, 1.37 Hz), 7.16-7.34 (5 H, m). 19F NMR δ 91.7
(s). 13C NMR δ 11.0 (dd, J ) 2.57, 1.43 Hz), 31.3, 38.1 (dd, J
) 4.01, 2.86 Hz), 67.0, 123.7 (q, J ) 272.9 Hz), 126.0, 126.4
(q, J ) 24.5 Hz), 128.2, 128.3, 134.7 (dd, J ) 11.0, 5.44 Hz),
140.9. IR (neat) ν 670, 747, 892, 1030, 1118, 1177, 1335, 1455,
6,6-D i flu o r o -5,7-d i m e t h y l-1-p h e n y ln o n -4-e n -3-o l
(6bc): IR (neat) ν 698, 735, 911, 1018, 1072, 1197, 1383, 1457,
2878, 2933, 2967, 3380 cm-1. Anal. Calcd for C17H24F2O: C,
72.31; H, 8.57. Found: C, 72.73; H, 8.98. (E1 isom er + E2
isom er ):(Z1 isom er + Z2 isom er ) ) 89:11. E1 isom er :E2
isom er ) 50:50. 13C NMR δ 11.8, 11.9, 11.9 (dd, J ) 5.15,
4.01 Hz), 12.2 (dd, J ) 4.58, 4.58 Hz), 12.5 (t, J ) 3.15 Hz),
22.3 (dd, J ) 4.72, 4.01 Hz), 22.5 (dd, J ) 4.72, 3.00 Hz), 31.6,
38.7, 38.7, 39.5 (t, J ) 25.3 Hz), 39.5 (t, J ) 25.3 Hz), 67.5,
124.2 (t, J ) 245.1 Hz), 124.2 (t, J ) 245.1 Hz), 124.2 (t, J )
246.3 Hz), 125.8, 128.2, 128.3, 131.8 (t, J ) 8.87 Hz), 131.8 (t,
J ) 8.87 Hz), 132.1 (t, J ) 22.6 Hz), 132.1 (t, J ) 22.6 Hz),
141.4, 141.4. E1 isom er : 1H NMR δ 0.93 (3 H, t, J ) 7.63
J . Org. Chem, Vol. 69, No. 22, 2004 7623

Ueki et al.
Hz), 0.96 (3 H, d, J ) 6.91 Hz), 1.09-2.06 (5 H, m), 1.67 (3 H,
s), 2.66 (1 H, ddd, J ) 13.7, 9.21, 6.60 Hz), 2.75 (1 H, ddd, J
) 13.7, 9.34, 6.59 Hz), 4.43 (1 H, qt, J ) 7.19, 1.35 Hz), 5.80
(1 H, dq, J ) 8.52, 1.65 Hz), 7.15-7.32 (5 H, m). 19F NMR δ
52.6 (1 F, dd, J ) 236.5, 15.3 Hz), 53.4 (1 F, dd, J ) 236.5,
15.3 Hz). E2 isom er : 1H NMR δ 0.93 (3 H, t, J ) 7.36 Hz),
0.98 (3 H, d, J ) 6.83 Hz), 1.09-2.06 (5 H, m), 1.67 (3 H, s),
2.66 (1 H, ddd, J ) 13.7, 9.21, 6.60 Hz), 2.75 (1 H, ddd, J )
13.7, 9.34, 6.59 Hz), 4.43 (1 H, qt, J ) 7.19, 1.35 Hz), 5.80 (1
H, dq, J ) 8.52, 1.65 Hz), 7.15-7.32 (5 H, m). 19F NMR δ 52.2
(1 F, dd, J ) 238.0, 15.3 Hz), 54.3 (1 F, dd, J ) 236.5, 15.3
Hz). Z1 isom er :Z2 isom er ) 54:46. Z1 isom er : 1H NMR δ
0.90 (3 H, t, J ) 7.23 Hz), 0.91-1.00 (3 H, m), 1.09-2.06 (5 H,
m), 1.79 (3 H, s), 2.60-2.80 (2 H, m), 4.52 (1 H, m), 5.53 (1 H,
dd, J ) 8.28, 0.22 Hz), 7.15-7.32 (5 H, m). 19F NMR δ 59.7 (1
F, dd, J ) 245.7, 16.8 Hz), 61.5 (1 F, dd, J ) 245.7, 15.3 Hz).
Z2 isom er : 1H NMR δ 0.90 (3 H, t, J ) 7.23 Hz), 0.91-1.00
(3 H, m), 1.09-2.06 (5 H, m), 1.79 (3 H, s), 2.60-2.80 (2 H,
m), 4.52 (1 H, m), 5.53 (1 H, dd, J ) 8.28, 0.22 Hz), 7.15-7.32
(5 H, m). 19F NMR δ 60.2 (1 F, dd, J ) 245.7, 15.3 Hz), 60.9 (1
F, dd, J ) 245.7, 15.3 Hz).
131.5 (dd, J ) 25.2, 24.9 Hz), 133.6 (dd, J ) 7.73, 7.44 Hz),
141.3, 143.7, 147.6 (dd, J ) 37.2, 36.1 Hz). IR (neat) ν 700,
737, 823, 884, 910, 1007, 1066, 1161, 1234, 1268, 1387, 1454,
1496, 1603, 2344, 2360, 2861, 2929, 3027, 3063, 3386, 3587
cm-1
.
5-E t h yl-6,6-d iflu or o-4-m et h yl-1-p h en ylh ep t -4-en -3-ol
(6ca ): IR (neat) ν 700, 738, 918, 1052, 1106, 1162, 1208, 1251,
1303, 1382, 1453, 1495, 1603, 1647, 1724, 2078, 2874, 2939,
2968, 3025, 3062, 3409, 3584 cm-1. Anal. Calcd for C16H22
-
F2O: C, 71.61; H, 8.26. Found: C, 71.36; H, 7.98. E isom er :
1H NMR δ 0.94 (3 H, t, J ) 7.45 Hz), 1.70 (3 H, t, J ) 18.1
Hz), 1.80 (3 H, t, J ) 3.18 Hz), 1.65-2.15 (4 H, m), 2.63 (1 H,
ddd, J ) 13.6, 9.34, 7.02 Hz), 2.80 (1 H, ddd, J ) 13.8, 10.3,
5.13 Hz), 4.58 (1 H, dd, J ) 8.78, 4.64 Hz), 7.16-7.32 (5 H,
m). 19F NMR δ 77.0 (1 F, q, J ) 18.3 Hz). 13C NMR δ 12.6 (t,
J ) 4.01 Hz), 15.1, 21.1 (t, J ) 5.15 Hz), 24.9 (dd, J ) 30.1,
29.9 Hz), 32.3, 36.8, 70.3, 123.1 (t, J ) 242.0 Hz), 125.8, 128.3,
134.3 (dd, J ) 22.6, 22.3 Hz), 137.5 (dd, J ) 4.86, 4.58 Hz),
141.4. Z isom er : 1H NMR δ 1.03 (3 H, t, J ) 7.57 Hz), 1.61 (3
H, t, J ) 18.2 Hz), 1.75 (3 H, t, J ) 2.45 Hz), 1.65-2.15 (4 H,
m), 2.54-2.65 (1 H, m), 2.77-2.83 (1 H, m), 4.72 (1 H, m),
7.16-7.32 (5 H, m). 19F NMR δ 79.8 (1 F, dq, J ) 245.7, 18.3
Hz), 82.1 (1 F, dq, J ) 244.2, 18.3 Hz). 13C NMR δ 12.3, 15.3,
22.2 (dd, J ) 5.44, 5.15 Hz), 26.2 (t, J ) 30.1 Hz), 32.4, 36.8,
70.3, 123.4 (t, J ) 240.1 Hz), 125.8, 128.3, 134.6 (dd, J ) 22.9,
22.6 Hz), 138.3 (dd, J ) 4.58, 4.01 Hz), 141.7.
6,6-D iflu o r o -5,7,7-t r im e t h y l-1-p h e n y lo c t -4-e n -3-o l
(6bd ): IR (neat) ν 699, 749, 825, 885, 916, 1004, 1031, 1068,
1095, 1163, 1203, 1250, 1368, 1397, 1454, 1486, 1496, 2344,
2352, 2879, 2979, 3027, 3063, 3374 cm-1. Anal. Calcd for
C
17H24F2O: C, 72.31; H, 8.57. Found: C, 72.47; H, 8.87. E
1
isom er : H NMR δ 1.04 (9 H, s), 1.73 (3 H, d, J ) 1.22 Hz),
1.80 (1 H, dddd, J ) 13.6, 9.89, 6.35, 5.62 Hz), 1.97 (1 H, dddd,
J ) 13.6, 9.64, 7.45, 5.98 Hz), 2.68 (1 H, ddd, J ) 13.8, 9.62,
6.35 Hz), 2.75 (1 H, ddd, J ) 13.9, 9.89, 5.99 Hz), 4.44 (1 H,
m), 5.71 (1 H, dsex, J ) 10.5, 1.34 Hz), 7.16-7.30 (5 H, m).
19F NMR δ 53.6 (1 F, d, J ) 235.0 Hz), 54.9 (1 F, d, J ) 235.0
Hz). 13C NMR δ 13.9 (t, J ) 4.58 Hz), 24.5 (t, J ) 4.01 Hz),
31.6, 38.6, 39.1 (dd, J ) 26.1, 25.8 Hz), 67.7, 125.1 (t, J ) 249.1
Hz), 125.8, 128.2, 128.3, 132.0 (t, J ) 25.5 Hz), 134.5 (t, J )
8.31 Hz), 141.4. Z isom er : 19F NMR δ 59.8 (1 F, d, J ) 244.3
Hz), 62.2 (1 F, d, J ) 244.3 Hz).
5-E t h yl-6,6-d iflu or o-4-m et h yl-1-p h en yld ec-4-en -3-ol
(6cb): IR (neat) ν 700, 749, 806, 910, 1001, 1040, 1116, 1161,
1265, 1319, 1381, 1455, 1496, 1604, 1653, 1943, 2844, 2381,
2874, 2960, 3027, 3064, 3096, 3383, 3587 cm-1. Anal. Calcd
for C19H28F2O: C, 73.51; H, 9.09. Found: C, 73.56; H, 9.44. E
isom er : 1H NMR δ 0.91 (3 H, t, J ) 7.21 Hz), 0.94 (3 H, t, J
) 7.21 Hz), 1.30-1.38 (2 H, m), 1.42-1.52 (2 H, m), 1.66-
2.18 (6 H, m), 1.79 (3 H, t, J ) 2.93 Hz), 2.62 (1 H, ddd, J )
13.7, 9.52, 6.84 Hz), 2.81 (1 H, ddd, J ) 13.7, 10.0, 5.37 Hz),
4.59 (1 H, dd, J ) 8.79, 4.76 Hz), 7.18-7.32 (5 H, m). 19F NMR
δ 67.6 (1 F, dt, J ) 241.1, 16.8 Hz), 68.4 (1 F, dt, J ) 239.6,
16.8 Hz). 13C NMR δ 12.6 (t, J ) 4.01 Hz), 14.0, 15.2, 21.4 (t,
J ) 5.16 Hz), 22.5, 24.1 (t, J ) 3.44 Hz), 32.3, 36.8, 37.4 (dd,
J ) 27.5, 27.2 Hz), 70.4, 124.6 (t, J ) 243.6 Hz), 125.8, 128.3,
128.3, 134.0 (dd, J ) 22.6, 22.3 Hz), 137.7 (dd, J ) 4.87, 4.58
Hz), 141.4. Z isom er : 19F NMR δ 70.8 (1 F, dt, J ) 247.2,
16.8 Hz), 72.2 (1 F, dt, J ) 242.6, 16.8 Hz).
6,6-D i flu o r o -5-m e t h y l-1,6-d i p h e n y lh e x -4-e n -3-o l
(6be): IR (neat) ν 653, 669, 698, 749, 766, 817, 877, 920, 989,
1051, 1161, 1182, 1257, 1319, 1388, 1452, 1496, 1603, 1955,
2345, 2360, 2861, 2927, 3027, 3063, 3356, 3553 cm-1. Anal.
Calcd for C19H20F2O: C, 75.47; H, 6.67. Found: C, 75.18; H,
1
6.40. E isom er : H NMR δ 1.66 (3 H, d, J ) 1.35 Hz), 1.70-
1.86 (1 H, m), 1.95 (1 H, dddd, J ) 13.7, 9.53, 7.57, 6.11 Hz),
2.64 (1 H, ddd, J ) 13.9, 9.40, 6.59 Hz), 2.73 (1 H, ddd, J )
13.8, 9.52, 5.98 Hz), 4.41 (1 H, m), 5.82 (1 H, dddd, J ) 8.67,
4.99, 3.52, 1.47 Hz), 7.13-7.48 (10 H, m). 19F NMR δ 64.6 (1
F, d, J ) 251.8 Hz), 65.2 (1 F, d, J ) 251.8 Hz). 13C NMR δ
12.0 (dd, J ) 2.58, 2.29 Hz), 31.5, 38.5 (t, J ) 1.15 Hz), 67.5,
120.8 (t, J ) 241.3 Hz), 125.5 (t, J ) 5.73 Hz), 125.8, 128.2,
128.2, 128.3, 129.7 (dd, J ) 2.00, 1.72 Hz), 132.6 (t, J ) 7.73
Hz), 133.5 (t, J ) 16.1 Hz), 135.8 (dd, J ) 27.7, 27.1 Hz), 141.3.
Z isom er : 1H NMR δ 1.70-1.89 (2 H, m), 1.84 (3 H, d, J )
1.34 Hz), 2.58 (1 H, ddd, J ) 13.9, 10.0, 6.60 Hz), 2.62-2.76
(1 H, m), 4.52 (1 H, m), 5.63 (1 H, dddd, J ) 9.28, 3.18, 1.59,
0.73 Hz), 7.13-7.48 (10 H, m). 19F NMR δ 73.8 (1 F, d, J )
259.4 Hz), 76.1 (1 F, d, J ) 259.4 Hz). 13C NMR δ 20.2 (t, J )
4.58 Hz), 31.6, 38.7, 67.4 (dd, J ) 3.72, 3.44 Hz), 121.1 (dd, J
) 241.5, 241.3 Hz), 125.1 (dd, J ) 5.44, 5.15 Hz), 125.7, 128.2,
128.2, 128.4, 130.0 (dd, J ) 2.01, 1.71 Hz), 135.4 (t, J ) 27.1
Hz), 135.6 (dd, J ) 3.73, 3.43 Hz), 136.5 (t, J ) 27.1 Hz), 141.5.
6,6-Diflu or o-6-fu r yl-5-m et h yl-1-p h en ylh ex-4-en -3-ol
(6bf), E isom er : 1H NMR δ 1.73 (3 H, d, J ) 1.22 Hz), 1.82
(1 H, dddd, J ) 13.7, 9.52, 6.71, 5.73 Hz), 1.98 (1 H, dddd, J
) 13.7, 9.28, 7.45, 6.11 Hz), 2.69 (1 H, ddd, J ) 13.8, 9.28,
6.59 Hz), 2.75 (1 H, ddd, J ) 13.8, 9.64, 6.10 Hz), 4.46 (1 H,
m), 5.87 (1 H, ddt, J ) 8.55, 3.81, 1.71 Hz), 6.42 (1 H, m), 6.59
(1 H, dd, J ) 3.18, 0.86 Hz), 7.15-7.35 (5 H, m), 7.46 (1 H,
m). 19F NMR δ 64.7 (1 F, d, J ) 265.5 Hz), 65.3 (1 F, d, J )
265.5 Hz). 13C NMR δ 11.9 (td, J ) 2.29, 0.86 Hz), 31.5, 38.4
(dd, J ) 1.44, 1.14 Hz), 67.5, 110.1 (td, J ) 3.29, 1.15 Hz),
110.3, 116.2 (dd, J ) 237.3, 237.0 Hz), 125.9, 128.3, 128.3,
5-Eth yl-6,6-d iflu or o-4,7,7-tr im eth yl-1-p h en yloct-4-en -
3-ol (6cd ), E isom er : 1H NMR δ 0.96 (3 H, t, J ) 7.42 Hz),
1.04 (9 H, s), 1.72 (1 H, dddd, J ) 14.0, 9.89, 6.87, 4.67 Hz),
1.83 (3 H, t, J ) 3.03 Hz), 1.90-2.20 (3 H, m), 2.65 (1 H, ddd,
J ) 13.5, 8.62, 6.87 Hz), 2.83 (1 H, ddd, J ) 13.7, 9.89, 5.22
Hz), 4.65 (1 H, dd, J ) 8.79, 4.67 Hz), 7.14-7.38 (5 H, m). 19F
NMR δ 58.4 (1 F, d, J ) 241.3 Hz), 60.8 (1 F, d, J ) 241.3 Hz).
13C NMR δ 13.7 (t, J ) 5.44 Hz), 16.3, 23.1 (dd, J ) 5.72, 5.44
Hz), 25.0 (t, J ) 3.73 Hz), 32.5, 37.0, 41.0 (t, J ) 26.1 Hz),
70.8, 125.9, 127.5 (dd, J ) 250.2, 249.9 Hz), 128.3, 128.3, 131.8
(t, J ) 22.6 Hz), 140.3 (t, J ) 4.30 Hz), 141.5. IR (neat) ν 700,
746, 921, 1006, 1059, 1073, 1090, 1118, 1161, 1252, 1366, 1397,
1454, 1487, 1748, 2877, 2965, 3027, 3063, 3397, 3587 cm-1
.
Anal. Calcd for C19H28F2O: C, 73.51; H, 9.09. Found: C, 73.38;
H, 9.38.
5-Eth yl-6,6-d iflu or o-4-m eth yl-1,6-d ip h en ylh ex-4-en -3-
ol (6ce): IR (neat) ν 699, 735, 770, 911, 982, 1022, 1065, 1092,
1117, 1176, 1236, 1255, 1302, 1321, 1380, 1452, 1495, 1604,
1719, 1735, 1812, 1959, 2875, 2936, 3027, 3064, 3406, 3583
cm-1. Anal. Calcd for C21H24F2O: C, 76.34; H, 7.32. Found:
C, 75.91; H, 7.67. E isom er : 1H NMR δ 1.00 (3 H, t, J ) 7.45
Hz), 1.61 (3 H, t, J ) 2.87 Hz), 1.74 (1 H, dddd, J ) 14.4, 10.0,
6.84, 4.52 Hz), 2.02 (1 H, dtd, J ) 14.2, 9.64, 5.24 Hz), 2.06-
2.25 (2 H, m), 2.65 (1 H, ddd, J ) 13.6, 9.65, 6.84 Hz), 2.83 (1
H, ddd, J ) 13.6, 10.0, 5.25 Hz), 4.69 (1 H, dd, J ) 8.79, 4.39
Hz), 7.03-7.56 (10 H, m). 19F NMR δ 77.8 (1 F, d, J ) 265.5
Hz), 78.8 (1 F, d, J ) 265.6 Hz). 13C NMR δ 13.3 (t, J ) 2.58
Hz), 15.0, 21.7 (t, J ) 4.58 Hz), 32.3, 36.9 (dd, J ) 1.43, 1.14
Hz), 70.4, 121.8 (dd, J ) 241.3, 241.1 Hz), 125.5 (t, J ) 4.87
7624 J . Org. Chem., Vol. 69, No. 22, 2004

Regioselective SN2′ Reaction of F2-Vinyloxiranes
Hz), 125.9, 128.3, 128.3, 129.8 (t, J ) 2.01 Hz), 133.1 (dd, J )
23.5, 23.2 Hz), 137.5 (t, J ) 28.2 Hz), 140.3 (dd, J ) 5.44, 5.16
19F NMR δ 74.1 (1 F, d, J ) 260.9 Hz), 77.3 (1 F, d, J ) 260.9
Hz). 13C NMR δ 20.3 (t, J ) 4.43 Hz), 69.8 (t, J ) 4.01 Hz),
121.2 (t, J ) 241.8 Hz), 125.4 (t, J ) 5.30 Hz), 125.9, 127.8,
128.4, 128.5, 130.2 (t, J ) 1.83 Hz), 132.3 (t, J ) 26.1 Hz),
134.7 (t, J ) 3.44 Hz), 136.4 (t, J ) 27.9 Hz), 142.6.
1
Hz), 141.4. Z isom er : H NMR δ 1.11 (3 H, t, J ) 7.33 Hz),
1.67-1.85 (1 H, m), 1.83 (3 H, dd, J ) 2.81, 2.56 Hz), 1.70-
2.07 (1 H, m), 2.06-2.38 (2 H, m), 2.58 (1 H, ddd, J ) 15.6,
11.0, 4.64 Hz), 2.80-2.87 (1 H, m), 4.40 (1 H, dt, J ) 9.51,
3.60 Hz), 7.03-7.56 (5 H, m). 19F NMR δ 80.8 (1 F, d, J )
265.5 Hz), 83.8 (1 F, d, J ) 267.0 Hz). 13C NMR δ 13.6, 15.0,
22.7 (t, J ) 4.72 Hz), 32.3, 36.1, 70.4, 121.6 (t, J ) 239.3 Hz),
125.5 (t, J ) 4.87 Hz), 125.9, 128.2, 128.2, 129.9 (t, J ) 1.71
Hz), 133.7 (t, J ) 22.9 Hz), 138.4 (t, J ) 28.1 Hz), 140.7 (dd,
J ) 5.44, 6.01, 5.44 Hz), 141.6.
3-(1,1-Diflu or oet h yl)-1,5,5-t r im et h ylcycloh ex-2-en -1-
1
ol (6ea ): H NMR δ 1.02 (3 H, s), 1.05 (3 H, s), 1.32 (3 H, s),
1.56 (1 H, d, J ) 14.3 Hz), 1.69 (1 H, ddd, J ) 14.3, 1.38, 1.10
Hz), 1.70 (3 H, t, J ) 18.3 Hz), 1.84 (1 H, dq, J ) 17.0, 1.92
Hz), 1.95 (1 H, dquint, J ) 17.0, 1.24 Hz), 5.92 (1 H, brs). 19F
NMR δ 68.0 (1 F, dq, J ) 248.7, 18.3 Hz), 68.8 (1 F, dq, J )
250.4, 18.3 Hz). 13C NMR δ 22.8 (dd, J ) 29.2, 28.9 Hz), 27.3,
30.0, 30.6, 30.9 (dd, J ) 1.14, 0.86 Hz), 36.9 (dd, J ) 2.29,
2.00 Hz), 49.9, 68.7, 121.5 (t, J ) 236.5 Hz), 129.6 (t, J ) 8.01
Hz), 134.3 (t, J ) 24.9 Hz). IR (neat) ν 809, 876, 910, 1061,
1137, 1174, 1277, 1379, 1458, 1678, 1720, 2338, 2363, 2874,
2956, 3379, 3590 cm-1. Anal. Calcd for C11H18F2O: C, 64.68;
H, 8.88. Found: C, 64.57; H, 8.57.
4,4-Diflu or o-3-m eth yl-1-p h en ylp en t-2-en -1-ol (6d a ): IR
(neat) ν 699, 759, 921, 1007, 1075, 1136, 1178, 1226, 1299,
1385, 1450, 1493, 1604, 1674, 1716, 1812, 1887, 1956, 2929,
3003, 3032, 3063, 3311, 3584 cm-1. Anal. Calcd for C12
-
H14F2O: C, 67.91; H, 6.65. Found: C, 68.00; H, 6.70. E isom er :
1
cm-1: H NMR δ 1.71 (3 H, dd, J ) 18.4, 18.1 Hz), 1.86 (3 H,
d, J ) 1.10 Hz), 5.48 (1 H, dt, J ) 8.52, 1.38 Hz), 6.02 (1 H,
dddd, J ) 8.52, 5.22, 3.57, 1.65 Hz), 7.25-7.41 (5 H, m). 19F
NMR δ 69.1 (qt, J ) 18.1, 3.01 Hz). 13C NMR δ 11.8 (dd, J )
3.15, 2.86 Hz), 22.8 (t, J ) 29.2 Hz), 70.0, 121.8 (t, J ) 237.0
Hz), 125.9, 127.7, 128.5, 130.4 (dd, J ) 8.59, 8.30 Hz), 133.6
(dd, J ) 24.9, 24.7 Hz), 142.4 (t, J ) 1.15 Hz). Z isom er : 1H
NMR δ 1.77 (3 H, t, J ) 18.4 Hz), 1.82 (3 H, s), 5.64 (1 H, dt,
J ) 9.90, 1.38 Hz), 5.69 (1 H, d, J ) 9.89 Hz), 7.25-7.41 (5 H,
m). 19F NMR δ 75.4 (1 F, dq, J ) 244.7, 18.1 Hz), 77.4 (1 F,
dq, J ) 245.6, 18.1 Hz). 13C NMR δ 19.8 (dd, J ) 5.17, 4.87
Hz), 24.7 (t, J ) 29.2 Hz), 69.6 (t, J ) 4.58 Hz), 122.6 (t, J )
241.1 Hz), 125.9, 127.5, 128.4, 133.0 (m), 133.6 (m), 142.8.
4,4-Diflu or o-3-m eth yl-1-p h en yloct-2-en -1-ol (6d b): IR
(neat) ν 698, 735, 910, 1007, 1116, 1171, 1327, 1382, 1454,
1601, 1674, 2871, 2934, 2960, 3031, 3359, 3584 cm-1. Anal.
Calcd for C15H20F2O: C, 70.84; H, 7.93. Found: C, 70.90; H,
8.35. E isom er : 1H NMR δ 0.89 (3 H, t, J ) 7.10 Hz), 1.20-
1.40 (3 H, m), 1.83 (3 H, d, J ) 1.73, Hz), 1.80-2.00 (3 H, m),
5.50 (1 H, d, J ) 8.52 Hz), 6.02 (1 H, dsex, J ) 8.52, 1.65 Hz),
7.26-7.40 (5 H, m). 19F NMR δ 61.1 (1 F, dt, J ) 240.0, 16.8
Hz), 61.7 (1 F, dt, J ) 241.0, 16.8 Hz). 13C NMR δ 12.2 (t, J )
3.15 Hz), 13.9, 22.4, 24.4 (dd, J ) 4.31, 4.01 Hz), 35.3 (dd, J )
27.9, 27.6 Hz), 70.1, 122.9 (dd, J ) 241.3, 240.5 Hz), 125.9,
127.6, 128.5, 130.9 (t, J ) 8.59 Hz), 132.4 (t, J ) 24.1 Hz),
142.5. Z isom er : 19F NMR δ 67.7 (1 F, dt, J ) 244.9, 16.8
Hz), 69.7 (1 F, dt, J ) 244.1, 16.8 Hz).
4,4-Diflu or o-3,5,5-tr im eth yl-1-ph en ylh ex-2-en -1-ol (6dd):
IR (neat) ν 567, 668, 699, 736, 763, 825, 892, 912, 942, 1004,
1031, 1063, 1077, 1096, 1196, 1259, 1368, 1385, 1398, 1455,
1465, 1485, 1950, 2248, 2350, 2364, 2879, 2979, 3031, 3064,
3087, 3346 cm-1. Anal. Calcd for C15H20F2O: C, 70.84; H, 7.93.
Found: C, 71.19; H, 7.85. E isom er : 1H NMR δ 1.01 (9 H, s),
1.86 (3 H, d, J ) 1.34 Hz), 5.48 (1 H, d, J ) 8.30 Hz), 5.95 (1
H, dsex, J ) 8.49, 1.34 Hz), 7.27-7.45 (5 H, m). 19F NMR δ
53.6 (1 F, d, J ) 235.0 Hz), 54.4 (1 F, d, J ) 235.0 Hz). 13C
NMR δ 14.1 (dd, J ) 4.58, 4.30 Hz), 24.5 (dd, J ) 4.01, 3.72
Hz), 39.3 (t, J ) 25.8 Hz), 70.5, 125.1 (t, J ) 249.3 Hz), 125.9,
127.7, 128.6, 132.0 (dd, J ) 25.8, 25.5 Hz), 134.1 (t, J ) 8.59
Hz), 142.5. Z isom er : 19F NMR δ 59.6 (1 F, d, J ) 244.1 Hz),
63.6 (1 F, d, J ) 245.7 Hz).
3-(1,1-Diflu or op en tyl)-1,5,5-tr im eth ylcycloh ex-2-en -1-
ol (6eb): 1H NMR δ 0.92 (3 H, dd, J ) 7.42, 6.86 Hz), 1.01 (3
H, s), 1.05 (3 H, s), 1.31 (3 H, s), 1.24-1.48 (6 H, m), 1.55 (1
H, d, J ) 14.3 Hz), 1.69 (1 H, dt, J ) 14.3, 1.37 Hz), 1.81-
1.92 (2 H, m), 5.91 (1 H, brs). 19F NMR δ 60.5 (1 F, dt, J )
242.1, 16.4 Hz), 61.7 (1 F, dt, J ) 242.1, 16.4 Hz). 13C NMR δ
13.9, 22.4, 24.3 (dd, J ) 4.29, 4.01 Hz), 27.3, 30.0, 30.7, 31.0
(dd, J ) 1.15, 0.86 Hz), 35.2 (t, J ) 26.6 Hz), 37.3 (dd, J )
2.58, 2.29 Hz), 49.8, 68.7, 122.6 (dd, J ) 240.5, 240.2 Hz), 130.0
(t, J ) 8.31 Hz), 133.4 (t, J ) 24.3 Hz). IR (neat) ν 810, 837,
879, 907, 1004, 1060, 1112, 1172, 1270, 1314, 1345, 1370, 1462,
1677, 1723, 2339, 2364, 2872, 2958, 3376, 3593 cm-1. Anal.
Calcd for C14H24F2O: C, 68.26; H, 9.82. Found: C, 68.44; H,
9.44.
3-(1,1-Diflu or o-2,2-d im eth ylp r op yl)-1,5,5-tr im eth ylcy-
cloh ex-2-en -1-ol (6ed ): 1H NMR δ 1.00 (3 H, s), 1.05 (9 H, s),
1.07 (3 H, s), 1.32 (3 H, s), 1.55 (1 H, d, J ) 13.9 Hz), 1.69 (1
H, dt, J ) 14.2, 1.34 Hz), 1.87 (1 H, brd, J ) 17.1 Hz), 2.20 (1
H, dd, J ) 17.3, 1.16 Hz), 5.84 (1 H, dt, J ) 2.32, 1.10 Hz). 19
F
NMR δ 52.4 (1 F, d, J ) 238.1 Hz), 55.5 (1 F, d, J ) 236.5 Hz).
13C NMR δ 24.5 (t, J ) 4.01 Hz), 27.2, 30.4, 30.9, 31.2, 39.0 (t,
J ) 3.44 Hz), 39.3 (t, J ) 25.8 Hz), 49.9, 68.8, 124.8 (dd, J )
248.8, 247.6 Hz), 133.1 (dd, J ) 26.1, 23.2 Hz), 133.3 (dd, J )
8.87, 7.73 Hz). IR (KBr) ν 517, 562, 579, 743, 795, 824, 840,
884, 894, 906, 937, 990, 1013, 1032, 1078, 1110, 1166, 1189,
1249, 1349, 1370, 1486, 1495, 1542, 1560, 2346, 2979, 3316
cm-1. Anal. Calcd for C14H24F2O: C, 68.26; H, 9.82. Found:
C, 68.32; H, 9.61. Mp 65 °C.
3-(1,1-Diflu or o-1-p h en ylm eth yl)-1,5,5-tr im eth ylcyclo-
h ex-2-en -1-ol (6ee): 1H NMR δ 0.95 (3 H, s), 0.97 (3 H, s),
1.31 (3 H, s), 1.55 (1 H, d, J ) 14.3 Hz), 1.68 (1 H, brd, J )
14.3 Hz), 1.77 (1 H, ddd, J ) 17.0, 3.57, 1.92 Hz), 1.87 (1 H,
brd, J ) 17.0 Hz), 5.95 (1 H, m), 7.38-7.52 (5 H, m). 19F NMR
δ 62.3 (1 F, d, J ) 252.5 Hz), 65.2 (1 F, d, J ) 251.6 Hz). 13C
NMR δ 27.2, 30.1, 30.6, 31.0, 36.9, 49.9, 68.7, 120.5 (t, J )
240.8 Hz), 125.5 (dd, J ) 6.01, 5.72 Hz), 128.2, 129.7, 131.2 (t,
J ) 7.73 Hz), 134.2 (t, J ) 26.3 Hz), 135.7 (t, J ) 27.8 Hz). IR
(neat) ν 668, 699, 754, 768, 804, 832, 880, 905, 978, 1025, 1051,
1111, 1163, 1187, 1220, 1262, 1369, 1388, 1452, 2350, 2368,
2926, 2956, 3404 cm-1. Anal. Calcd for C16H20F2O: C, 72.16;
H, 7.57. Found: C, 72.05; H, 7.94.
4,4-Diflu r o-3-m et h yl-1-(4-m et h ylp h en yl)oct -2-en -1-ol
(6gb): IR (neat) ν 669, 721, 762, 818, 894, 912, 943, 1009,
1087, 1117, 1170, 1263, 1327, 1382, 1457, 1513, 2873, 2933,
2960, 3344. Anal. Calcd for C16H22F2O: C, 71.61; H, 8.26.
Found: C, 71.27; H, 8.31. E isom er : 1H NMR δ 0.89 (3 H, t,
J ) 7.20 Hz), 1.29-1.42 (4 H, m), 1.81 (3 H, d, J ) 1.35 Hz),
1.86-1.96 (2 H, m), 2.35 (3H, s), 5.46 (1 H, m), 6.02 (1 H, ddq,
J ) 8.42, 3.05, 1.35 Hz), 7.23-7.27 (4 H, m). 19F NMR δ 61.4
(2 F, td, J ) 16.8, 4.58 Hz). 13C NMR δ 12.2 (t, J ) 3.15 Hz),
13.9, 21.2, 22.4, 24.4 (t, J ) 4.15 Hz), 35.3 (t, J ) 26.4 Hz),
70.1, 122.9 (t, J ) 241.3 Hz), 125.9, 129.2, 132.0 (t, J ) 23.9
Hz), 132.3 (t, J ) 23.9 Hz), 137.4, 139.6. Z isom er : 1H NMR
δ 0.92 (3 H, t, J ) 7.20 Hz), 1.42-1.52 (4 H, m), 1.81 (3 H, m),
4,4-Diflu or o-3-m eth yl-1,4-d ip h en ylbu t-2-en -1-ol (6d e):
IR (neat) ν 632, 659, 698, 746, 766, 845, 890, 919, 990, 1072,
1159, 1206, 1257, 1319, 1385, 1452, 1493, 1540, 1604, 1811,
1890, 1957, 2346, 2927, 2957, 3033, 3064, 3087, 3347 cm-1
.
Anal. Calcd for C17H16F2O: C, 74.44; H, 5.88. Found: C, 74.44;
H, 6.27. E isom er : 1H NMR δ 1.79 (3 H, d, J ) 1.46 Hz), 5.48
(1 H, d, J ) 8.42 Hz), 6.07 (1 H, dd, J ) 8.42, 1.37 Hz), 7.25-
7.55 (10 H, m). 19F NMR δ 64.5 (1 F, d, J ) 251.8 Hz), 65.3 (1
F, d, J ) 251.8 Hz). 13C NMR δ 12.2 (t, J ) 2.29 Hz), 70.3,
120.8 (t, J ) 241.5 Hz), 125.5 (t, J ) 5.73 Hz), 125.9, 127.8,
128.2, 128.6, 129.7 (t, J ) 1.83 Hz), 132.1 (t, J ) 8.02 Hz),
133.3 (t, J ) 26.1 Hz), 135.7 (t, J ) 27.9 Hz), 142.8. Z isom er :
1H NMR δ 1.85 (3 H, t, J ) 1.46 Hz), 5.63 (1 H, d, J ) 9.15
Hz), 5.83 (1 H, dd, J ) 9.76, 0.85 Hz), 7.25-7.55 (10 H, m).
J . Org. Chem, Vol. 69, No. 22, 2004 7625

Ueki et al.
1.86-2.02 (2 H, m), 2.34 (3 H, s), 5.62 (1 H, m), 5.68 (1 H,
dqd, J ) 9.53, 1.47, 0.74 Hz), 7.23-7.27 (4 H, m). 19F NMR δ
67.7 (1 F, dt, J ) 244.1, 16.8 Hz), 69.5 (1 F, dt, J ) 244.1, 16.8
Hz). 13C NMR δ 13.9, 20.1 (t, J ) 5.15 Hz), 21.2, 22.5, 24.0 (t,
J ) 3.87 Hz), 35.3 (t, J ) 26.8 Hz), 70.1 (t, J ) 4.58 Hz), 123.9
(t, J ) 278.1 Hz), 125.8, 129.1, 132.4 (dd, J ) 25.3, 24.5 Hz),
133.7 (t, J ) 3.34 Hz), 137.2, 140.0.
249.4 Hz). IR (neat) ν 668, 700, 734, 826, 911, 951, 1004, 1030,
1051, 1176, 1243, 1275, 1301, 1380, 1419, 1454, 1495, 1603,
2342, 2361, 2860, 2926, 3026, 3061, 3385, 3568 cm-1. Anal.
Calcd for C17H21F2OS2: C, 62.93; H, 6.52. Found: C, 61.86;
H, 6.56.
3,4-E p oxy-5-e t h yl-6-flu or o-4-m e t h yl-1-p h e n yld e c-5-
en e (8c): IR (neat) ν 698, 821, 861, 906, 1078, 1135, 1191,
6,6-Diflu or o-5-m eth yl-1-p h en yl-3-(2-p h en yleth yl)d ec-
4-en -3-ol (6ib), E isom er : 1H NMR δ 0.86-0.96 (3 H, m),
1.20-1.50 (6 H, m), 1.84-2.08 (7 H, m), 2.62-2.84 (4 H, m),
5.80 (1 H, sex, J ) 1.65 Hz), 7.10-7.36 (10 H, m). 19F NMR δ
62.4 (td, J ) 16.4, 2.15 Hz). 13C NMR δ 12.5 (t, J ) 2.86 Hz),
14.0, 22.5, 24.9 (t, J ) 4.30 Hz), 30.3, 35.5 (t, J ) 27.2 Hz),
44.2, 76.3, 123.5 (t, J ) 242.2 Hz), 125.9, 128.2, 128.4, 132.4
(t, J ) 8.88 Hz), 132.9 (t, J ) 22.9 Hz), 141.9. IR (neat) ν 669,
699, 748, 910, 1030, 1117, 1170, 1266, 1318, 1380, 1454, 1491,
1507, 1603, 1617, 1624, 1636, 1648, 1654, 1675, 1685, 1696,
1700, 1718, 1734, 1869, 1943, 2344, 2362, 2871, 2957, 3026,
1223, 1255, 1379, 1457, 1496, 1696, 1701, 2871, 2962 cm-1
.
Ma jor isom er : 1H NMR δ 0.91 (3 H, t, J ) 7.33 Hz), 1.04 (3
H, t, J ) 7.56 Hz), 1.32 (2 H, sex, J ) 7.74 Hz), 1.37 (3 H, s),
1.47 (2 H, quint, J ) 7.70 Hz), 1.82-2.30 (6 H, m), 2.74-2.92
(3 H, m), 7.16-7.32 (5 H, m). 19F NMR δ 49.8 (t, J ) 22.9 Hz).
13C NMR δ 14.0 (d, J ) 4.01 Hz), 14.0 (d, J ) 4.01 Hz), 18.6
(d, J ) 1.14 Hz), 19.7 (d, J ) 6.58 Hz), 22.5, 28.5, 29.4 (d, J )
27.1 Hz), 30.7, 32.7, 60.6 (d, J ) 11.0 Hz), 63.7 (d, J ) 0.86
Hz), 119.3 (d, J ) 16.9 Hz), 126.0, 128.2, 128.4, 140.9, 157.1
(d, J ) 251.4 Hz). Min or isom er : 1H NMR δ 0.92 (3 H, t, J
) 7.33 Hz), 1.06 (3 H, td, J ) 7.56, 0.86 Hz), 1.27-1.39 (2 H,
m), 1.40 (3 H, s), 1.47-1.55 (2 H, m), 1.82-2.30 (6 H, m), 2.74-
2.92 (3 H, m), 7.16-7.32 (5 H, m). 19F NMR δ 55.2 (t, J ) 22.9
Hz). 13C NMR δ 14.5 (d, J ) 3.15 Hz), 14.5 (d, J ) 3.15 Hz),
18.9 (d, J ) 3.15 Hz), 20.4 (d, J ) 5.73 Hz), 22.2, 28.2 (d, J )
28.3 Hz), 28.7, 30.9, 32.4, 59.6 (d, J ) 6.59 Hz), 64.0 (d, J )
1.58 Hz), 119.5 (d, J ) 13.6 Hz), 125.8, 128.1, 128.2, 141.4,
155.6 (d, J ) 247.9 Hz).
3062, 3085, 3447 cm-1
.
4,4-Diflu or o-3-(2-p h en ylet h yl)oct -2-en -1-ol (6jb ): IR
(neat) ν 700, 751, 833, 909, 999, 1065, 1083, 1115, 1171, 1224,
1267, 1325, 1382, 1455, 1496, 1604, 1696, 1869, 1943, 2345,
2362, 2873, 2934, 2959, 3027, 3063, 3086, 3345 cm-1. Anal.
Calcd for C16H22F2O: C, 71.61; H, 8.26. Found: C, 71.97; H,
7.91. E isom er : 1H NMR δ 0.92 (3 H, t, J ) 7.14 Hz), 1.28-
1.50 (4 H, m), 1.88-2.06 (2 H, m), 2.39-2.46 (2 H, m), 2.73 (2
H, m), 3.93 (2 H, dt, J ) 6.60, 2.48 Hz), 5.93 (1 H, tt, J ) 6.59,
2.20 Hz), 7.17-7.37 (5 H, m). 19F NMR δ 64.6 (tq, J ) 16.6,
2.58 Hz). 13C NMR δ 13.9, 22.5, 24.5 (t, J ) 4.15 Hz), 28.9 (t,
J ) 2.29 Hz), 35.6, 36.1 (t, J ) 27.6 Hz), 58.7, 123.6 (dd, J )
242.1, 241.3 Hz), 126.1, 128.3, 128.7, 130.0 (t, J ) 8.88 Hz),
135.8 (t, J ) 23.5 Hz), 141.1. Z isom er : 1H NMR δ 0.91 (3 H,
dd, J ) 7.41, 6.87 Hz), 1.28-1.50 (4 H, m), 1.83-2.05 (2 H,
m), 2.32-2.44 (2 H, m), 2.74-2.82 (2 H, m), 4.29 (2 H, m),
5.61 (1 H, brt, J ) 6.31 Hz), 7.15-7.35 (5 H, m). 19F NMR δ
67.7 (tt, J ) 17.2, 3.02 Hz). 13C NMR δ 13.9, 22.5, 24.1 (t, J )
3.47 Hz), 34.5 (t, J ) 4.30 Hz), 35.4, 37.3 (t, J ) 27.1 Hz), 59.3
(t, J ) 5.44 Hz), 124.2 (dd, J ) 242.8, 243.1 Hz), 125.9, 128.2,
128.3, 131.6 (t, J ) 4.15 Hz), 136.0 (t, J ) 24.2 Hz), 141.1.
4,4-Diflu or o-1,3-d ip h en yloct-2-en -1-ol (6lb): IR (neat)
ν 700, 725, 760, 777, 822, 908, 1011, 1074, 1116, 1147, 1179,
1264, 1317, 1382, 1456, 1494, 1762, 1811, 1890, 1953, 2873,
2933, 2960, 3031, 3061, 3085, 3341, 3584 cm-1. Anal. Calcd
for C20H22F2O: C, 75.92; H, 7.01. Found: C, 76.09; H, 7.04. E
isom er : 1H NMR δ 0.84 (3 H, dd, J ) 7.41, 7.14 Hz), 1.19-
1.34 (2 H, m), 1.35-1.48 (2 H, m), 1.75-2.14 (2 H, m), 5.03 (1
H, d, J ) 9.07 Hz), 6.35 (1 H, dt, J ) 9.34, 1.92 Hz), 7.20-
7.38 (10 H, m). 19F NMR δ 69.7 (1 F, dt, J ) 241.7, 16.8 Hz),
64.2 (1 F, dt, J ) 241.7, 16.4 Hz). 13C NMR δ 13.4, 22.3, 24.2
(t, J ) 4.01 Hz), 35.6 (dd, J ) 26.3, 26.1 Hz), 70.8, 122.1 (t, J
) 243.1 Hz), 126.0, 127.8, 128.1, 128.2, 128.5, 129.5, 132.8 (dd,
J ) 8.59, 8.30 Hz), 138.1 (dd, J ) 23.5, 23.2 Hz), 138.3 (dd, J
) 2.87, 2.57 Hz), 142.3. Z isom er : 1H NMR δ 0.83 (3 H, dd,
J ) 7.42, 7.14 Hz), 1.19-1.34 (2 H, m), 1.35-1.48 (2 H, m),
1.75-2.14 (2 H, m), 5.87 (1 H, brd, J ) 9.34 Hz), 5.93 (1 H,
dd, J ) 9.34, 0.82 Hz), 7.20-7.38 (10 H, m). 19F NMR δ 70.9
(1 F, dt, J ) 249.0, 16.4 Hz), 72.0 (1 F, dt, J ) 249.0, 16.4 Hz).
13C NMR δ 13.4, 22.3, 23.4 (t, J ) 3.72 Hz), 37.7 (dd, J ) 26.3,
26.1 Hz), 69.9 (dd, J ) 6.01, 5.44 Hz), 123.6 (t, J ) 243.9 Hz),
126.1, 127.7, 127.7, 128.1, 128.7 (dd, J ) 1.43, 1.15 Hz), 134.1
(t, J ) 2.00 Hz), 137.4 (dd, J ) 24.6, 24.3 Hz), 142.7.
5-E t h yl-6-flu or o-4-m e t h yle n e -1-p h e n yld e c-5-e n -3-ol
(9c): IR (neat) ν 699, 749, 785, 808, 910, 942, 972, 1067, 1120,
1191, 1222, 1254, 1322, 1379, 1430, 1454, 1497, 1604, 1636,
1685, 1943, 2345, 2362, 2873, 2932, 2964, 3027, 3063, 3096,
3361 cm-1. Anal. Calcd for C19H27FO: C, 78.58; H, 9.37.
Found: C, 78.27; H, 9.33. Ma jor isom er : 1H NMR δ 0.87 (3
H, t, J ) 7.33 Hz), 0.91 (3 H, t, J ) 7.44 Hz), 1.22-1.56 (4 H,
m), 1.70 (1 H, dtd, J ) 14.0, 9.89, 4.95 Hz), 1.95 (1 H, dddd, J
) 13.9, 10.2, 6.87, 3.30 Hz), 2.15-2.37 (4 H, m), 2.70 (1 H,
ddd, J ) 13.7, 9.89, 6.84 Hz), 2.85 (1 H, ddd, J ) 13.8, 10.1,
4.95 Hz), 4.16 (1 H, dd, J ) 9.28, 2.69 Hz), 4.91 (1 H, m), 5.33
(1 H, d, J ) 1.47 Hz), 7.16-7.31 (5 H, m). 19F NMR δ 51.5 (dd,
J ) 24.4, 22.9 Hz). 13C NMR δ 13.0 (d, J ) 1.71 Hz), 14.0,
20.4 (d, J ) 7.45 Hz), 22.5, 29.3 (d, J ) 28.1 Hz), 29.4, 32.2,
37.3, 71.9 (d, J ) 3.43 Hz), 113.3 (d, J ) 2.01 Hz), 119.1 (d, J
) 18.9 Hz), 125.8, 128.3, 128.3, 141.6, 148.6 (d, J ) 8.01 Hz)
157.1 (d, J ) 251.9 Hz). Min or isom er : 19F NMR δ 57,2 (dd,
J ) 24.9, 22.9 Hz).
2-Ben zylid en e-4-flu or o-3-m eth yloct-3-en -1-ol (9h ): IR
(neat) ν 669, 700, 759, 827, 875, 922, 1038, 1121, 1169, 1219,
1379, 1458, 1466, 1491, 1647, 1653, 1685, 1700, 2345, 2363,
2872, 2930, 2958, 3023, 3057, 3392, 3587 cm-1. Anal. Calcd
for C16H21FO: C, 77.38; H, 8.52. Found: C, 76.90; H, 8.67.
1
Ma jor isom er : H NMR δ 0.95 (3 H, t, J ) 7.14 Hz), 1.25-
1.47 (2 H, m), 1.48-1.64 (2 H, m), 1.87 (3 H, d, J ) 2.75 Hz),
2.30-2.38 (1 H, m), 2.38-2.48 (1 H, m), 4.39 (2 H, d, J ) 5.77
Hz), 6.61 (1 H, s), 7.23-7.40 (5 H, m). 19F NMR δ 57.6 (brt, J
) 24.1 Hz). 13C NMR δ 14.0, 16.6 (d, J ) 5.72 Hz), 22.2, 28.9
(d, J ) 1.14 Hz), 29.3 (d, J ) 29.5 Hz), 60.8 (d, J ) 4.58 Hz),
112.2 (d, J ) 14.3 Hz), 127.0, 128.1, 128.9, 131.1 (d, J ) 2.57
Hz), 136.5, 138.4, 156.6 (d, J ) 249.1 Hz). Min or isom er : 1H
NMR δ 0.90 (3 H, t, J ) 7.14 Hz), 1.25-1.47 (2 H, m), 1.48-
1.64 (2 H, m), 1.84 (3 H, m), 2.30-2.38 (1 H, m), 2.38-2.48 (1
H, m), 4.34 (2 H, d, J ) 4.94 Hz), 6.48 (1 H, s), 7.23-7.40 (5
H, m). 19F NMR δ 54.7 (brt, J ) 24.1 Hz). 13C NMR δ 13.6 (d,
J ) 8.30 Hz), 14.0, 22.5, 29.2 (d, J ) 28.1 Hz), 29.4 (d, J )
0.86 Hz), 59.5 (d, J ) 2.86 Hz), 113.9 (d, J ) 19.5 Hz), 127.1,
128.2, 128.6, 130.7 (d, J ) 2.29 Hz), 136.2, 139.2 (d, J ) 8.30
Hz), 157.9 (d, J ) 252.8 Hz).
6-(1,3-Dith ian -2-yliden e)-6-flu or o-5-m eth yl-1-ph en ylh ex-
4-en -3-ol (7), E isom er : 1H NMR δ 1.83 (3 H, d, J ) 1.37
Hz), 1.84 (1 H, dddd, J ) 13.5, 9.07, 6.87, 6.04 Hz), 1.99 (1 H,
m), 2.13 (2 H, quint, J ) 6.04 Hz), 2.73 (1 H, d, J ) 7.97 Hz),
2.75 (1 H, dd, J ) 7.14, 1.65 Hz), 2.81 (1 H, dt, J ) 5.49, 1.92
Hz), 2.83 (1 H, ddd, J ) 6.05, 2.75, 1.65 Hz), 2.94 (2 H, m),
4.48 (1 H, m), 5.72 (1 H, ddt, J ) 8.51, 3.02, 1.37 Hz), 7.15-
7.35 (5 H, m). 19F NMR δ 70.3 (m). 13C NMR δ 14.3 (d, J )
1.44 Hz), 24.7, 28.7 (d, J ) 2.00 Hz), 29.9 (d, J ) 0.68 Hz),
31.5, 38.6, 67.7 (m), 109.3 (d, J ) 29.5 Hz), 125.7, 127.6 (d, J
) 27.8 Hz), 128.2, 137.4 (d, J ) 6.88 Hz), 141.5, 156.0 (d, J )
5-B u t y l-4-e t h y l-3-m e t h y l-2-(2-p h e n y le t h y l)fu r a n
(10c): 1H NMR δ 0.93 (3 H, t, J ) 7.33 Hz), 1.04 (3 H, t, J )
7.57 Hz), 1.34 (2 H, sex, J ) 7.32 Hz), 1.57 (2 H, quint, J )
7.45 Hz), 1.71 (3 H, s), 2.26 (2 H, q, J ) 7.57 Hz), 2.51 (2 H, t,
J ) 7.45 Hz), 2.78 (2 H, m), 2.86 (2 H, m), 7.10-7.28 (5 H, m).
13C NMR δ 8.23, 14.1, 15.5, 17.0, 22.5, 25.9, 28.4, 31.4, 35.1,
114.5, 120.1, 125.7, 128.1, 128.4, 141.6, 147.1, 148.3. IR (neat)
ν 698, 749, 957, 1056, 1121, 1139, 1253, 1379, 1454, 1496, 1595,
7626 J . Org. Chem., Vol. 69, No. 22, 2004

Regioselective SN2′ Reaction of F2-Vinyloxiranes
1604, 2344, 2360, 2860, 2870, 2930, 2960, 3027, 3062 cm-1
Anal. Calcd for C19H26O: C, 84.39; H, 9.69. Found: C, 84.11;
H, 9.38.
.
3339. Anal. Calcd for C12H12F2O: C, 68.56; H, 5.75. Found:
C, 68.80; H, 5.71.
Su p p or tin g In for m a tion Ava ila ble: Preparation of R,â-
unsaturated ketones (Table 6 and Scheme 7) and R,â-epoxy
ketones (Table 7 and Scheme 8) and some of their physical
properties, as well as MOPAC computational details (Figures
3 and 5: energetic preference of the reaction of 1 with
monomeric MeLi from both re- and si-face attack; Figure 4:
transition states of the reaction of 1 with monomeric MeLi,
followed by the Cartesian coordinates for the obtained station-
ary points). This material is available free of charge via the
Internet at http://pubs.acs.org.
(E)-2-b en zylid en e-4,4-d iflu or o-3-m et h ylb u t -3-en -1-ol
(11h ): 1H NMR δ 1.71 (3 H, dd, J ) 3.30, 3.02 Hz), 4.28 (2 H,
brs), 6.63 (1 H, dd, J ) 3.03, 1.38 Hz), 7.20-7.32 (5 H, m). 19
F
NMR δ 69.7 (1 F, dddd, J ) 43.9, 4.74, 3.01, 1.73 Hz), 72.7 (1
F, ddd, J ) 43.9, 7.46, 3.44 Hz). 13C NMR δ 12.5 (dd, J ) 2.29,
0.86 Hz), 65.9 (dd, J ) 3.44, 2.29 Hz), 83.9 (dd, J ) 22.1, 19.5
Hz), 127.4, 128.1, 128.3, 128.7 (dd, J ) 2.86, 1.43 Hz), 134.2
(dd, J ) 3.87, 2.72 Hz), 136.1, 152.0 (dd, J ) 287.6, 284.9 Hz).
IR (neat) ν 669, 695, 755, 872, 924, 1014, 1074, 1093, 1125,
1198, 1260, 1448, 1491, 1648, 1740, 2345, 2364, 2929, 3026,
J O049025X
J . Org. Chem, Vol. 69, No. 22, 2004 7627