Stereoselective generation of cis-2-lithio-3-CF3-oxirane via CF3-substituted β-oxido carbenoids. Highly stereoselective synthesis of CF3-substituted tri- and tetrasubstituted oxiranes and tetrasubstituted alkenes

Article abstract of DOI:10.1016/j.tet.2003.09.098

Treatment of 2-substituted 3,3-dichloro-1,1,1-trifluoropropan-2-ols with organolithium reagents R²Li in THF at -98°C stereoselectively produces 2,3-disubstituted 2-lithio-3-trifluoromethyloxiranes with Li and CF₃ cis. The reagents react with electrophiles El-X or organoboranes R³BR₂ to give CF₃-containing tri- and tetrasubstituted oxiranes or tetrasubstituted alkenes, respectively, with high diastereoselectivities.

Full text of DOI:10.1016/j.tet.2003.09.098

Tetrahedron 59 (2003) 9811–9823
Stereoselective generation of cis-2-lithio-3-CF3-oxirane via
CF3-substituted b-oxido carbenoids. Highly stereoselective
synthesis of CF3-substituted tri- and tetrasubstituted oxiranes
and tetrasubstituted alkenes
*
Masaki Shimizu, Takuya Fujimoto, Xinyu Liu, Hiroshi Minezaki, Takeshi Hata and
Tamejiro Hiyama
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Received 6 August 2003; revised 1 September 2003; accepted 1 October 2003
Abstract—Treatment of 2-substituted 3,3-dichloro-1,1,1-trifluoropropan-2-ols with organolithium reagents R2Li in THF at 2988C
stereoselectively produces 2,3-disubstituted 2-lithio-3-trifluoromethyloxiranes with Li and CF3 cis. The reagents react with electrophiles
El-X or organoboranes R3BR2 to give CF3-containing tri- and tetrasubstituted oxiranes or tetrasubstituted alkenes, respectively, with high
diastereoselectivities.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
Oxiranyllithiums have been emerging as highly versatile
reagents for the stereocontrolled synthesis of functionalized
oxiranes as well as alkenes.1 Strategies for generation of
oxiranyllithiums recorded so far are divided into two
categories: one involves deprotonation of an oxirane with
a base, and the other is exchange of heteroatoms such as
sulfur and tin with lithium (Scheme 1). Both methods are
synthetically valuable and widely utilized, while stereo-
defined oxiranes, whose preparations often require robust
efforts, are essential as precursors for stereoselective
generation of oxiranyllithiums.
Scheme 1. Generation of oxiranyllithiums.
On the other hand, intramolecular cyclization of b-oxido
lithium carbenoids can, in principle, be the third strategy
without cyclization to produce the corresponding lithium
enolate whose hydrolysis gave a homologated aldehyde in a
that is quite unique since acyclic precursors are employed in
good yield (Scheme 2).2e,h Thus, intramolecular cyclization
place of cyclic ones (Scheme 1). b-Oxido carbenoids
of dihalohydrins leading to oxiranyllithiums is still to be
explored.3
generated from dihalohydrins (R3¼halogen) with a base,
however, reportedly undergo 1,2-rearrangement of a sub-
stituent attached at the carbinol carbon, giving rise to
carbonyl compounds.2 For instance, treatment of benzal-
dehyde with dichloromethyllithium in THF at 2958C
followed by the addition of BuLi at 2958C generated
phenyl-substituted b-oxide carbenoid in which, upon
warming to 08C, a phenyl group migrated in 1,2-fashion
Keywords: carbenoids; fluorine; lithium; oxirane; trifluoromethyl.
*
Corresponding author. Tel.: þ81-75-753-5535; fax: þ81-75-753-5555;
e-mail: shimizu@npc05.kuic.kyoto-u.ac.jp
Scheme 2. Rearrangement of b-oxido carbenoid.
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.09.098

9812
M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
In the course of our study on the novel synthesis of
organofluorine compounds utilizing fluorine-containing
carbenoid reagents,4 we focused our attention on novel
CF3-substituted b-oxido carbenoids and have found that the
carbenoids are capable of the realization of the third strategy
(Scheme 1).5 We describe herein novel generation of
oxiranyllithiums 3 from acyclic dichlorohydrins 1 and
their reactions with an electrophile, providing convenient
and versatile synthetic methods of preparing CF3-containing
tri- and tetrasubstituted oxiranes 4 and tetrasubstituted
alkenes 5 and 6 (Scheme 3).6
2.2. Synthesis of tri- and tetrasubstituted oxiranes 4
Whereas the rearrangement of b-oxido carbenoids gener-
ated from dihalohydrins is applicable to homologation of
not only aldehydes and ketones but esters (via b-oxido
alkylidene-type carbenoids), no precedent is available for
CF3-substituted ketones. Hence, we became interested in a
reaction of b-oxido carbenoids 2 to develop a novel method
for synthesis of CF3-containing target compounds. Thus, we
first treated 1a with 3 molar amounts of BuLi in THF at
2788C and then warmed the reaction mixture to room
temperature before quenching with MeOH in a manner
similar to the reported procedure2e,h (Eq. (2), R2¼Bu).
Unexpectedly, (E)-allylic alcohol 7 was obtained as the sole
product in 58% yield (Table 2, entry 1). No products derived
from the expected CF3 or Ph(CH2)2 rearrangement were
detected. When the same reaction was effected and
quenched at 2788C, oxirane 4a was isolated in 33% yield
along with 7 (58% yield, entry 2). Moreover, lowering the
reaction temperature to 2988C gave 4a solely in 85% yield
as a single diastereomer (entry 3).
ð2Þ
Scheme 3. Novel and stereoselective generation and reactions of CF3-
substituted oxiranyllithiums 3.
Table 2. Reaction of 1a with BuLi (R2¼Bu)a
Entry
R1
Temperature (8C)
Isolated yield
2. Results and discussion
4a (%)
7 (%)
1
2
3
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
278 to rt
278
298
0
33
85
58
58
–
2.1. Preparation of CF3-containing dichlorohydrins 1
Dichlorohydrins 1 were readily prepared by treatment of
freshly distilled 3,3-dichloro-1,1,1-trifluoropropan-2-one
with Grignard reagents R1MgBr in THF at 08C (Eq. (1)).
The results are summarized in Table 1. Various kinds of
substituent R1 were easily introduced in moderate to good
yields. In contrast, use of the corresponding organolithium
reagents (R1Li) resulted in the low yields of 1 probably
because deprotonation of the ketone by R1Li competed with
the carbonyl addition.
a
To a solution of 1 (1.0 mmol) in THF (5 mL) was added R2Li (3.0 mmol)
at the temperature indicated. The solution was allowed to warm to room
temperature (entry 1) or stirred at the temperature for 15 min before
quenching with methanol (entries 2 and 3).
Under the same conditions, formation of oxirane of type 4
was general irrespective of substituents R1 and R2 (Eq. (2)
and Table 3). Thus, the reaction of dichlorohydrins 1b–d
afforded the corresponding oxiranes 4b–d in good yields
with good to high diastereoselectivity. In addition to BuLi,
Table 3. Synthesis of trisubstituted oxiranes 4a
ð1Þ
Run
1
R1
R2
4
Yield (%)b Isomer ratioc
1
2
3
4
5
6
7
8
1b (E)-PhCHvCH Bu
4b
4c
4d
4e
4f
74
84
83
93
87
95
85
67
83:17
.95:,5
89:11
.95:,5
.95:,5
.95:,5
.95:,5
.95:,5
Table 1. Preparation of dichlorohydrins 1a
1c PhCuC
1d Ph
1a Ph(CH2)2
Bu
Bu
Ph
R1
1
Yield (%)b
1b (E)-PhCHvCH Ph
Ph(CH2)2
(E)-PhCHvCH
PhCuC
Ph
1a
1b
1c
1d
59
88
86
80
1c PhCuC
1c PhCuC
1c PhCuC
Ph
Me
C2H3 4i
4g
4h
a
To a solution of 1 (1.0 mmol) in THF (5 mL) was added R2Li (3.0 mmol)
at 2988C. The solution was stirred at 2988C for 15 min before quenching
with methanol at 2988C. For entries 4–6, the reaction mixture was
allowed to warm to 2788C before quenching with methanol at 2788C.
Isolated yields.
a
To a 1.0 M THF solution of R1MgBr (30 mmol) was added freshly
distilled 3,3-dichloro-1,1,1-trifluoropropan-2-one (3.2 mL, 28 mmol) at
08C. The mixture was stirred for 10–30 min at 08C and stirred at room
temperature overnight.
b
c
b
1
Isolated yields based on the ketone.
Determined by H and 19F NMR analysis.

M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
9813
phenyllithium, methyllithium, and vinyllithium also reacted
with 1a–c to give 4e–i stereoselectively. No reaction took
place with phenylethynyllithium, while complex mixture
resulted when s-BuLi or t-BuLi was employed with 1. In all
cases, no product derived from the rearrangement was
observed. A solvent mixture of THF/Et2O/pentane (4:1:1)
was also effective for the production of 4, whereas use of
such solvent(s) as Et2O, Et2O/TMEDA, hexane, and
hexane/TMEDA resulted in the low conversion of 1 and/
or the low yield of 4. In addition, when 2 molar amounts of
R2Li were employed, 4 was produced in moderate yields
with recovery of 1.
Since product distribution of 4a and 7 was dependent on the
reaction temperature as shown in Table 2, we considered
that oxiranyllithiums 3 should be produced as an intermedi-
ate at 2988C (for discussion of the mechanism, see Section
2.3). Accordingly, we treated 1 with BuLi or PhLi in THF at
2988C and then with an electrophile at 2988C. The
resulting mixture was allowed to warm to 2788C and
quenched with MeOH at 2788C. We found that silylation
with chlorotrimethylsilane, borylation with (isopropoxy)-
(pinacolato)borane, aldehyde addition, ketone addition, and
allylation with allyl bromide proceeded smoothly to give the
corresponding tetrasubstituted oxiranes 4j–r in good yields
with excellent diastereoselectivity (Table 4). These results
clearly demonstrate the generation of 3 from acyclic 1 and
the realization of the third strategy in Scheme 1.
Scheme 4. Stereodivergent synthesis of tetrasubstituted oxiranes 4.
Table 4. Synthesis of tetrasubstituted oxiranes 4a
Run
R1
R2
Elb
4
Yield (%)c Isomer ratiod
1
2
3
4
5
6
7
8
9
PhCuC
Bu Me3Si
4j
79
62
76
82
71
68
57
55
70
.95:,5
.95:,5
.95:,5
PhCuC
PhCuC
PhCuC
PhCuC
PhCuC
Ph(CH2)2
Bu B(OCMe2)2 4k
Ph B(OCMe2)2 4l
Bu PhCH(OH) 4m
Bu Et2C(OH)
Bu Ph2C(OH) 4o
Bu Ph2C(OH) 4p
e
–
4n
.95:,5
.95:,5
.95:,5
89:11
(E)-PhCHvCH Bu Ph2C(OH) 4q
PhCuC Bu C3H5 4r
.95:,5
a
To a solution of 1 (1.0 mmol) in THF (5 mL) was added R2Li (3 mmol) at
2988C and the mixture was stirred at 2988C for 15 min before adding
El-X (1.5 mmol). The resulting solution was gradually warmed to
2788C and quenched with MeOH at 2788C.
El-X employed were as follows: entry 1, Me3SiCl; entries 2 and 3,
(i-PrO)B(OCMe2)2; entry 4, PhCHO; entry 5, Et2CO; entries 6–8,
Ph2CO; entry 9, allyl bromide.
In the case of alkylation, both diastereomers of tetrasub-
stituted oxiranes 4 can be prepared by proper choice of R2Li
and El-X. For example, treatment of 1c with BuLi and then
iodomethane in HMPA afforded 4s, while another diaster-
eomer 4s0 was obtained by methyllithium-induced gener-
ation of 3 followed by trapping with iodobutane in HMPA
as illustrated in Scheme 4.7
b
c
d
e
Isolated yield.
Determined by 1H and 19F NMR analysis.
Two of four possible diastereomers were obtained in a ratio of 60:40.
Stereochemistry of 4 was determined by X-ray crystal-
lographic analysis of benzophenone adducts 4o and 4q in
which a CF3 group and Ph2C(OH) were cis (Fig. 1).8 These
results clearly indicate that oxiranyllithiums 3 were
stereoselectively generated as intermediates with CF3 and
Li being cis in all cases.9
Figure 1. ORTEP drawings of 4o and 4q.

9814
M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
2.3. Mechanism for the generation of 3
the third R2Li was a rate-determining step. At tempera-
tures above 2788C, 3 would cause ring-opening via a-
elimination of lithium and oxygen to generate a carbene
which would undergo adjacent C–H bond insertion with
R2¼Bu, giving rise to 7.
The mechanism for the stereoselective generation of 3
from 1 is proposed in Scheme 5. At first, 1 would react
with 2 molar amounts of R2Li to produce b-oxido
carbenoid 2. We assume that 2 favors a conformation in
which a CF3 group and a lithium atom connecting a
carbenoid carbon are positioned synclinal due to lithium–
fluorine chelation.10 Starting from the Li–F chelated
conformer 2, there are two plausible pathways. Substi-
tution of chlorine in 2 with the third R2Li from the OLi
side would produce 20 which would undergo intramole-
cular cyclization to generate 3 that was stable at 2988C
and reacted with an electrophile producing 4. Alterna-
tively, cyclization of 2 would take place at first to
generate chlorolithiooxirane 200 which might form oxo-
nium ion 2000 by participation of a lone pair of electrons in
oxygen. Subsequently, the third R2Li would add to the
carbon substituted by a lithium atom to afford 3 with
retention of configuration of 200.11 The fact that 3 was
generated at some extent with remaining 1 by use of 2
molar amounts of R2Li indicated that deprotonation by
2.4. Reaction of b-MgO carbenoids leading to CF3-con-
taining tetrasubstituted alkenes 8
So far, we have demonstrated that b-LiO carbenoids react
with an organolithium reagent to generate oxiranyllithiums
3 via intramolecular cyclization. We expected that changing
lithium to magnesium might suppress the intramolecular
cyclization and perform rearrangement reaction of b-oxido
carbenoids. Thus, we treated 1a with MeMgBr in THF at
2788C to prepare the corresponding magnesium alkoxide.
To the solution, we added 3 molar amount of MeLi at
2788C and warmed the mixture to room temperature
(Scheme 6). No rearranged product, however, formed but
tetrasubstituted alkene 8a was obtained in 60% yield (Table
5, entry 1). The alkene formation was applicable to 1b–d
and BuLi as R2Li as shown in Table 5 although the yields of
8b and 8c were low.
2.5. Stereoselective synthesis of CF3-containing tetra-
substituted alkenes 5 and 6
Regio- and stereoselective synthesis of tetrasubstituted
alkenes is a challenging issue in organic synthesis.12
Oxiranyllithiums are reported to react with such organome-
tallic reagents as RLi, R3Al, R2Zn, and R4CeLi to give
alkylated alkenes.13 We envisioned that CF3-containing
tetrasubstituted alkenes should be synthesized stereoselec-
tively if such transformation would be applicable to 3. Then,
we examined a reaction of 3 with various kinds of
organometallic reagents. Treatment of 1c with more than
3 molar amounts of BuLi followed by warming to room
Scheme 6. Reaction of CF3-substituted b-MgO lithium carbenoids.
Table 5. Synthesis of tetrasubstituted alkenes 8a
Entry
1
R1
R2
8
Yield (%)b
1
2
3
4
5
6
7
1a
1b
1b
1c
1c
1d
1d
Ph(CH2)2
(E)-PhCHvCH
(E)-PhCHvCH
PhCuC
PhCuC
Ph
Me
Me
Bu
Me
Buc
Me
Bu
8a
8b
8c
8d
8e
8f
60
15
26
55
71
69
60
Ph
8g
a
To a THF (3 mL) solution of 1 (1.0 mmol) was added R2MgBr
(1.0 mmol) at 2788C. After stirred at 2788C for 1 h, the solution was
added R2Li (3.0 mmol) at 2788C and was allowed to warm to room
temperature before quenching with saturated aqueous NH4Cl solution.
Isolated yields.
b
c
Scheme 5. Proposed mechanism for the stereoselective generation and
reactions of oxiranyllithiums 3.
BuMgCl was used instead of BuMgBr.

M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
9815
Table 6. Stereoselective synthesis of tetrasubstituted alkenes 5 (R1¼
PhCuC)a
Entry
R2
R3
5
Yield (%)b
Isomer ratio
1
2
3
4
Bu
Bu
Bu
Ph
PhCuC
(E)-BuCH¼CH
5c
5d
5e
5e0
74
56
66
84
.95: ,5
.95: ,5
97: 3
Ph
Bu
96: 4
a
To a solution of 1c (1.0 mmol) in THF (5 mL) was added BuLi (1.50 M,
2.0 mL, 3.0 mmol) at 2988C. The solution was stirred at 2988C for
15 min and then was added R3B(OCMe2)2 (2.0 mmol) at 2988C. The
resulting solution was gradually warmed to room temperature and then
refluxed for 4h before quenching with aqueous saturated NH4Cl solution.
Isolated yield.
b
temperature and quenching with MeOH produced only 7,
indicating that no reaction of 3 (R2¼Bu) occurred.14 When
3 (R2¼Bu) was treated with Me3Al or Et2Zn, methylated or
ethylated alkene 5a or 5b was obtained in low yields,
respectively. On the other hand, triethylborane reacted with
3 (R2¼Bu) to afford 5b in 45% yield with excellent
stereoselectivity (.95%).15 Furthermore, (pinacolato)bor-
ane exhibited better reactivity (Eq. (3)). Thus, alkynyl,
alkenyl, aryl, and alkyl groups were applicable to this
stereospecific formation of 5 as a R3 substituent (Table 6).
Noteworthy is that appropriate combination of R2 and R3
allows us to prepare either stereoisomer of 5 at will as
demonstrated in entries 3 and 4.
Scheme 7. Stereodivergent synthesis of b-CF3-substituted alkenylboro-
nates 6 (R1¼PhCuC, B¼B(OCMe2)2, Si¼SiMe2Ph).
the diboron at 2988C followed by warming the solution to
room temperature gave stereoselectively 6E in which CF3
and boryl group were arranged cis, respectively. On the
other hand, alkenylboronates 6Z was stereoselectively
produced in favor of 6E or b-CF3-substituted alkenylsilane
9 when the silylborane was employed.
ð3Þ
Stereoselective formation of 6E or 6Z can be explained by
assuming a syn-elimination of LiOB or LiOSi at the last step
as illustrated in Scheme 8. First, 3 should react with borane
reagent R3-B to give borate 10 in which 1,2-migration of
substituent R3 would take place and cause the ring-opening
to generate lithium alkoxide 11. In cases of alkyl, alkenyl,
alkynyl, aryl, and boryl groups for R3, minimum rotation for
eclipsing carbon–boron and carbon–oxygen bonds would
lead to 12 from which 6E was produced by syn-elimination
of LiOB.17 When the silylborane was employed (i.e. R3 in
11 was the silyl group), the carbon–boron bond should turn
by 1808 for LiOSi to eliminate in cis fashion, giving rise to
6Z.18
Since a CF3 and a phenyl groups in 5e were shown to be cis
by X-ray analysis (Fig. 2),8 stereochemistry of 5 was
assumed to be similar: CF3 group and R3 substituent are
always cis.
Finally, reaction of 3 with bis(pinacolato)diboron and
(dimethylphenylsilyl)(pinacolato)borane were studied to
prepare b-CF3-substituted alkenylboronates (Scheme 7).16
Thus, treatment of a THF solution of 3 (R2¼Bu or Ph) with
3. Conclusion
We have demonstrated that CF3-substituted oxiranyl-
lithiums can be generated from readily available acyclic
CF3-containing dichlorohydrins and organolithium reagents
via novel reaction of b-oxido carbenoids. Noteworthy is that
the generation proceeds with high stereoselectivity that
involves CF3 and Li being cis. The oxiranyllithiums react
stereospecifically not only with various kinds of electro-
philes to give tri- and tetrasubstituted oxiranes but also with
organoborane reagents to afford tetrasubstituted alkenes,
which serve as highly versatile intermediates for stereo-
controlled synthesis of CF3-containing complex organic
molecules which are receiving much attention in pharma-
ceutical and material sciences.19
Figure 2. ORTEP drawing of 5e.

9816
M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
Scheme 8. Proposed mechanism for stereodivergent formation of tetrasubstituted alkenes 6 (B¼B(OCMe2)2, Si¼SiMe2Ph).
4. Experimental
4.1. General remarks
4.3. General procedure for the preparation of dichloro-
hydrin 1
To a THF solution of R1MgBr (30 mmol, 1.0 M) was added
freshly distilled 3,3-dichloro-1,1,1-trifluoropropan-2-one
(3.2 mL, 28 mmol) at 08C. The mixture was stirred for
10–30 min at 08C and stirred at room temperature over-
night. The reaction mixture was quenched with saturated
aqueous NH4Cl solution and the aqueous layer was
extracted with diethyl ether three times. The combined
organic layer was dried over anhydrous MgSO4 and
concentrated in vacuo to give the crude compound, which
was purified by column chromatography on silica gel
(hexane/ethyl acetate 10:1) giving rise to 1.
Melting points were determined using a Yanagimoto Micro
1
Melting Point Apparatus. H NMR spectra were measured
on a Varian Mercury 200 (200 MHz) spectrometer. The
chemical shifts of 1H NMR are expressed in parts per
million downfield relative to the internal tetramethylsilane
(d¼0 ppm) or chloroform (d¼7.26 ppm). Splitting patterns
are indicated as s, singlet; d, doublet; t, triplet; q, quartet;
brs, broad singlet. 13C NMR spectra were measured on a
Varian Mercury 200 (50 MHz) spectrometer with tetra-
methylsilane as an internal standard (d¼0 ppm) or chloro-
form-d (d¼77.0 ppm). 19F NMR spectra were measured on
a Varian Mercury 200 (188 MHz) spectrometer with CFCl3
as an internal standard (d¼0 ppm). Chemical shift values
are given in parts per million downfield relative to the
internal standard. Infrared spectra (IR) were recorded on a
Shimadzu FTIR-8400 spectrometer. GC-MS analyses were
performed with a JEOL JMS-700 spectrometer by electron
ionization at 70 eV. Elemental analyses were carried out
with a YANAKO MT2 CHN CORDER machine at
Elemental Analysis Center of Kyoto University. TLC
analyses were performed by means of Merck Kieselgel 60
F254 and column chromatography was carried out using
Merck Kieselgel 60 (230–400 mesh). Preparative HPLC
was carried out with a Japan Analytical Industry Co., Ltd,
LC-908 chromatograph using a JAIGEL-1H and -2H GPC
columns. Tetrahydrofuran was distilled from benzophenone
and sodium before use under a nitrogen atmosphere. All
reactions were carried out under an argon atmosphere.
4.3.1. 1,1-Dichloro-2-trifluoromethyl-4-phenylbutan-2-
ol (1a). Yield: 59%. Colorless oil. Rf 0.22 (hexane/ethyl
acetate 10:1). 1H NMR d 2.30–2.41 (m, 2H), 2.80 (t,
J¼8.6 Hz, 2H), 2.95 (brs, 1H), 5.99 (s, 1H), 7.21–7.37 (m,
5H). 13C NMR d 28.6, 33.3, 72.9, 78.6 (q, J¼26.8 Hz),
124.3 (q, J¼287.0 Hz), 126.5, 128.3, 128.7, 140.2. 19F
NMR (188 MHz, CDCl3, d 273.5. IR (neat): 3540, 3034,
1951, 1805, 1601, 1503, 1461, 1329, 1184, 1122, 911, 810,
782, 740, 671 cm21. MS m/z 290 (2, Mþþ4), 288 (9, Mþþ2),
287 (2, Mþþ1), 286 (14, Mþ), 91 (100). Anal. calcd for
C11H9Cl2F3O: C, 46.02; H, 3.86. Found: C, 46.15; H, 3.80.
4.3.2. (E)-1,1-Dichloro-2-trifluoromethyl-4-phenyl-but-
3-en-2-ol (1b). Addition reaction of styrylmagnesium
bromide, prepared from a E/Z mixture of b-bromostyrene
(Aldrich), to 3,3-dichloro-1,1,1-trifluoropropan-2-one gave
a E/Z mixture of the corresponding adducts which was
separated by silica gel column chromatography. Yield:
88%. Pale yellow oil. Rf 0.26 (hexane/ethyl acetate 10:1).
1H NMR d 3.07 (brs, 1H), 6.01 (s, 1H), 6.38 (d, J¼15.9 Hz,
1H), 7.10 (d, J¼15.9 Hz, 1H), 7.34–7.55 (m, 5H). 13C NMR
d 72.9, 79.0 (q, J¼28.1 Hz), 119.0, 123.4 (q, J¼286.1 Hz),
127.1, 128.8, 129.1, 134.9, 136.8. 19F NMR d 275.3. IR
4.2. Materials
Anhydrous tetrahydrofuran was purchased from Kanto
Chemicals. Butyllithium in hexane, methyllithium in
diethyl ether, phenyllithium in cyclohexane/diethyl ether
were purchased from Aldrich or Kanto Chemicals, and
titrated according to the literature method prior to use. 3,3-
Dichloro-1,1,1-trifluoropropan-2-one was generously pro-
vided by Central Glass Co. Ltd.
(neat): 3540, 1646, 1489, 1450, 1182, 965, 744, 685 cm21
.
MS m/z 288 (0.6, Mþþ4), 286 (3, Mþþ2), 285 (0.7,
Mþþ1), 284 (5, Mþ), 201 (100). Anal. calcd for
C11H9Cl2F3O: C, 46.34; H, 3.18. Found: C, 46.51; H, 3.05.

M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
9817
4.3.3. 1,1-Dichloro-2-trifluoromethyl-4-phenylbut-3-yn-
2-ol (1c). Yield: 86%. Pale yellow oil. Rf 0.13 (hexane/ethyl
acetate 10:1). H NMR d 3.53 (s, 1H), 5.96 (s, 1H), 7.37–
7.43 (m, 3H), 7.52–7.57 (m, 2H). 13C NMR d 71.8, 76.1 (q,
J¼31.1 Hz), 79.0, 89.9, 120.1, 122.2 (q, J¼285.7 Hz),
128.5, 130.0, 132.3. 19F NMR d 275.6. IR (neat): 3554,
2241, 1601, 1487, 1436, 1355, 1201, 1105, 982, 803, 753,
710, 685 cm21. MS m/z 286 (0.4, Mþþ4), 284 (3, Mþþ2),
283 (0.5, Mþþ1), 282 (4, Mþ), 199 (100). Anal. calcd for
C11H7Cl2F3O: C, 46.67; H, 2.49. Found: C, 46.69; H, 2.69.
diastereomers (83:17). Colorless oil. Rf 0.61 (hexane/ethyl
1
acetate 10:1). Major (3R p,4S p)-diastereomer: H NMR d
1
0.90 (t, J¼7.0 Hz, 3H), 1.35–1.62 (m, 6H), 3.46 (t,
J¼5.6 Hz, 1H), 6.32 (d, J¼16.0 Hz, 1H), 6.81 (d,
J¼16.0 Hz, 1H), 7.32–7.54 (m, 5H). 13C NMR d 13.8,
22.2, 26.1, 27.9, 61.1 (q, J¼35.5 Hz), 62.0, 115.4, 123.5 (q,
J¼277.6 Hz), 126.7, 128.67, 128.71, 133.0, 136.8. 19F NMR
d 275.9. IR (neat): 2949, 2848, 1652, 1491, 1441, 1322,
1263, 1151, 972, 935, 741, 984 cm21. MS m/z 272 (0.6,
Mþþ2), 271 (8, Mþþ1), 270 (41, Mþ), 213 (100,
Mþ2CF3). Anal. calcd for C15H17F3O: C, 66.72; H, 6.32.
Found: C, 66.65; H, 6.34. Minor (3R p,4R p)-diastereomer
(assignable peaks only are shown): 1H NMR d 2.96 (t,
J¼5.4 Hz, 1H), 6.38 (d, J¼16.0 Hz, 1H), 6.76 (d,
J¼16.0 Hz, 1H). 19F NMR d 268.9.
4.3.4. 1,1-Dichloro-3,3,3-trifluoro-2-phenylpropan-2-ol
(1d). Yield: 80%. Colorless oil. Rf 0.25 (hexane/ethyl
acetate 10:1). 1H NMR d 3.50 (brs, 1H), 6.35 (s, 1H), 7.43–
7.47 (m, 3H), 7.57–7.62 (m, 2H). 13C NMR d 74.0, 80.3 (q,
J¼285.0 Hz), 123.7 (q, J¼125.7 Hz), 125.7, 128.7, 129.6,
134.0. 19F NMR d 273.1. IR (neat): 3550, 1456, 1310,
1163, 1075, 1004, 930, 789, 702, 645 cm21. MS m/z 262
(0.1, Mþþ4), 260 (0.5, Mþþ2), 259 (0.1, Mþþ1), 258 (1,
Mþ), 175 (100). Anal. calcd for C9H7Cl2F3O: C, 41.73; H,
2.72. Found: C, 42.02; H, 2.90.
4.4.4. (3R p,4S p)-3,4-Epoxy-1-phenyl-3-trifluoromethyl-
oct-1-yne (4c). Yield: 84%. Colorless oil. Rf 0.59
1
(hexane/ethyl acetate 10:1). H NMR d 0.95 (t, J¼7.2 Hz,
3H), 1.37–1.63 (m, 4H), 1.79–1.90 (m, 2H), 3.44 (t,
J¼6.0 Hz, 1H), 7.34–7.42 (m, 3H), 7.49–7.54 (m, 2H). 13C
NMR d 13.9, 22.3, 27.7, 28.6, 61.5, 54.0 (q, J¼40.4 Hz),
78.1, 88.1, 120.8, 122.0 (q, J¼276.2 Hz), 128.4, 129.6,
132.2. 19F NMR d 275.8. IR (neat): 2951, 2861, 2242,
1487, 1458, 1346, 1315, 1211, 1193, 1162, 1100, 1002, 924,
754, 721, 690 cm21. MS m/z 270 (0.3, Mþþ2), 269 (2,
Mþþ1), 268 (11, Mþ), 199 (4, Mþ2CF3), 182 (100). Anal.
calcd for C15H15F3O: C, 67.16; H, 5.64. Found: C, 66.98; H,
5.71.
4.4. General procedure for the preparation of trisub-
stituted oxiranes 4
To a solution of 1 (1.0 mmol) in THF (5 mL) was added
R2Li (3.0 mmol) at 2988C. The solution was stirred at
2988C for 15 min before quenching with methanol. To the
reaction mixture was added saturated aqueous NH4Cl
solution, and the aqueous layer was extracted with diethyl
ether three times. Combined organic layer was dried over
anhydrous MgSO4 and concentrated in vacuo to give a crude
product. Purification by column chromatography on silica
gel (hexane/diethyl ether 10:1) gave 4.
4.4.5. (1R p,2S p)-1,2-Epoxy-1-phenyl-1-trifluoromethyl-
hexane (4d). Yield: 83% of a mixture of both diastereomers
(89:11). Colorless oil. Rf 0.59 (hexane/ethyl acetate 10:1).
Major (1R p,2S p)-diastereomer: 1H NMR d 0.82 (t,
J¼7.0 Hz, 3H), 1.02–1.63 (m, 6H), 3.51 (t, J¼7.0 Hz,
1H), 7.39–7.46 (m, 5H). 13C NMR d 13.7, 22.2, 27.7, 27.9,
60.7, 62.0 (q, J¼35.5 Hz), 123.6 (q, J¼277.3 Hz), 126.7,
128.4, 129.0, 129.7. 19F NMR d 275.0. IR (neat): 2951,
2925, 2860, 1756, 1678, 1451, 1179, 1068, 903, 762, 721,
701 cm21. MS m/z 246 (1, Mþþ2), 245 (13, Mþþ1), 244
(100, Mþ), 187 (59, Mþ2Bu), 175 (55, Mþ2CF3). Anal.
calcd for C13H15F3O: C, 63.93; H, 6.19. Found: C, 63.82; H,
6.09. Minor (1R p,2R p)-diastereomer (only assignable peaks
4.4.1. (3R p,4S p)-3,4-Epoxy-1-phenyl-3-trifluoromethyl-
octane (4a). Yield: 85%. Colorless oil. Rf 0.54 (hexane/
1
ethyl acetate 10:1). H NMR d 0.94 (t, J¼6.8 Hz, 3H),
1.25–1.72 (m, 6H), 2.07 (t, J¼8.6 Hz, 2H), 2.86 (t,
J¼8.6 Hz, 1H), 3.26 (t, J¼6.0 Hz, 1H), 7.21–7.38 (m,
5H). 13C NMR d 13.8, 22.4, 27.3, 28.2, 28.3, 30.7, 59.6 (q,
J¼34.0 Hz), 59.7, 124.4 (q, J¼278.3 Hz), 126.3, 128.2,
128.6, 140.9. 19F NMR d 275.4. IR (neat): 2951, 1767,
1601, 1446, 1332, 1259, 1148, 1021, 943, 905, 804, 741,
691 cm21. MS m/z 274 (0.1, Mþþ2), 273 (1, Mþþ1), 272
(8, Mþ), 104 (100). Anal. calcd for C15H19F3O: C, 66.16; H,
7.03. Found: C, 66.29; H, 6.96.
1
are shown): H NMR d 2.94–3.01 (m, 1H). 19F NMR d
266.7.
4.4.6. (1R p,2S p)-1,2-Epoxy-1,4-diphenyl-2-trifluoro-
methylbutane (4e). Yield: 93%. Colorless oil. Rf 0.58
1
4.4.2. 1-Phenyl-3-trifluoromethyloct-4-en-3-ol (7). Yield:
1
58%. Colorless oil. Rf 0.28 (hexane/ethyl acetate 10:1). H
(hexane/ethyl acetate 10:1). H NMR d 1.84 (t, J¼8.6 Hz,
2H), 2.69 (m, 2H), 4.41 (s, 1H), 6.88 (m, 2H), 7.12–7.25 (m,
3H), 7.30–7.42 (m, 5H). 13C NMR d 27.4, 30.5, 59.7, 61.7
(q, J¼34.3 Hz), 123.0 (q, J¼279.2 Hz), 126.1, 126.4, 128.1,
128.4, 128.5, 128.7, 132.6, 140.7. 19F NMR d 275.1. IR
(neat): 3064, 3028, 2939, 2871, 1604, 1496, 1456, 1344,
1168, 1147, 1037, 941, 918, 871, 698 cm21. MS m/z 293
(0.8, Mþþ1), 292 (5, Mþ), 201 (100). Anal. calcd for
C17H15F3O: C, 69.85; H, 5.17. Found: C, 69.85; H, 5.25.
NMR d 0.94 (t, J¼7.4 Hz, 3H), 1.26–1.60 (m, 2H), 1.92–
2.22 (m, 5H), 2.70 (t, J¼13.4 Hz, 2H), 5.57 (d, J¼15.6 Hz,
1H), 6.01 (dt, J¼15.6, 6.6 Hz, 1H), 7.19–7.38 (m, 5H). 13C
NMR d 15.1, 22.1, 28.6, 34.2, 35.6, 75.8 (q, J¼27.2 Hz),
125.7, 126.1, 128.3, 128.4, 128.5, 132.6 (q, J¼298.0 Hz),
141.4. 19F NMR d 282.1. IR (neat): 3470, 2950, 1600,
1500, 1450, 1260, 1170, 980, 750, 700 cm21. MS m/z 274
(0.3, Mþþ2), 273 (3, Mþþ1), 272 (19, Mþ), 91 (100). Anal.
calcd for C15H19F3O: C, 66.16; H, 7.03. Found: C, 66.39; H,
6.97.
4.4.7. (E)-(3R p,4S p)-3,4-Epoxy-1,4-phenyl-3-trifluoro-
methylbut-1-ene (4f). Yield: 87% as a colorless solid, mp
1
51–528C. Rf 0.58 (hexane/ethyl acetate 10:1). H NMR d
4.57 (s, 1H), 5.99 (d, J¼16.4 Hz, 1H), 6.87 (d, J¼16.4 Hz,
4.4.3. (3R p,4S p)-3,4-Epoxy-1-phenyl-3-trifluoromethyl-
(E)-oct-1-ene (4b). Yield: 74% of a mixture of both
1H), 7.25–7.32 (m, 5H). 13C NMR d 61.5, 62.7 (q,

9818
M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
J¼35.3 Hz), 114.5, 122.0 (q, J¼278.1 Hz), 126.8, 127.0,
128.2, 128.58, 128.62, 128.7, 135.2, 138.4. 19F NMR d
275.3. MS m/z 291 (6, Mþþ1), 290 (33, Mþ), 289 (3,
Mþ21), 105 (100). Anal. calcd for C17H13F3O: C, 70.34; H,
4.51. Found: C, 70.26; H, 4.46.
(t, J¼7.3 Hz, 3H), 1.30 (s, 12H), 1.17–1.60 (m, 4H), 1.81
(m, 1H), 1.98 (m, 1H), 7.31–7.37 (m, 3H), 7.46–7.48 (m,
2H). 13C NMR (125 MHz) d 13.8, 22.6, 24.5, 24.6, 27.8,
32.9, 57.2 (q, J¼40.2 Hz), 60.6, 79.2, 84.9, 88.1, 120.9,
121.2 (q, J¼276.2 Hz), 128.3, 129.4, 132.0. 19F NMR d
273.2. IR (neat): 3060, 2979, 2873, 2235, 1444, 1340,
1188, 1134, 1033, 850, 758 cm21. MS m/z 394 (4, Mþ), 393
(16, Mþ21), 310 (100). Anal. calcd for C21H26BF3O3: C,
63.98; H, 6.65. Found: C, 64.07; H, 6.42.
4.4.8. (3R p,4S p)-3,4-Epoxy-1,4-diphenyl-3-trifluoro-
methylbut-1-yne (4g). Yield: 95%. Colorless oil. Rf 0.50
(hexane/ethyl acetate 10:1). 1H NMR d 4.51 (s, 1H), 7.27–
7.36 (m, 4H), 7.37–7.52 (m, 6H). 13C NMR (CD3COCD3) d
57.4 (q, J¼40.2 Hz), 62.8, 78.5, 89.9, 121.2, 123.0 (q,
J¼276.2 Hz), 128.5, 129.2, 129.7, 130.5, 131.0, 132.6,
132.9. 19F NMR d 275.6. IR (neat): 3067, 3038, 2233,
1491, 1458, 1406, 1356, 1327, 1213, 1184, 1128, 1013, 916,
889, 756, 721, 696 cm21. MS m/z 288 (0.1, Mþþ2), 289 (3,
Mþþ1), 288 (18, Mþ), 219 (11, Mþ2CF3), 182 (100). Anal.
calcd for C17H11F3O: C, 70.83; H, 3.85. Found: C, 71.12; H,
3.96.
4.4.13. (3R p,4S p)-3,4-Epoxy-1,4-diphenyl-3-trifluoro-
methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)but-1-yne (4l). Yield: 76% as an off-white solid, mp
1
828C (dec). Rf 0.35 (hexane/ethyl acetate 10:1). H NMR
(500 MHz) d 1.25 (s, 6H), 1.26 (s, 6H), 7.02–7.04 (m, 2H),
7.14–7.18 (m, 2H), 7.22–7.26 (m, 1H), 7.30–7.38 (m, 3H),
7.54–7.57 (m, 2H). 13C NMR (125 MHz) d 24.3, 24.6, 59.1
(q, J¼40.2 Hz), 61.6, 78.8, 85.2, 88.3, 120.6, 121.0 (q,
J¼276.2 Hz), 126.5, 127.9, 128.1 (2C), 129.3, 131.9, 134.8.
19F NMR d 273.2. MS m/z 415 (4, Mþþ1), 414 (16, Mþ),
413 (16, Mþ21), 331 (100). Anal. calcd for C23H22BF3O3:
C, 66.69; H, 5.35. Found: C, 66.65; H, 5.54.
4.4.9. (3R p,4S p)-3,4-Epoxy-1-phenyl-3-trifluoromethyl-
pent-1-yne (4h). Yield: 85%. Colorless oil. Rf 0.49
1
(hexane/ethyl acetate 10:1). H NMR d 1.57 (d, J¼5.2 Hz,
3H), 3.57 (q, J¼5.2 Hz, 1H), 7.27–7.37 (m, 3H), 7.41–7.55
(m, 2H). 13C NMR d 14.4, 54.3 (q, J¼40.2 Hz), 57.6, 77.9,
88.3, 120.7, 121.9 (q, J¼276.3 Hz), 128.4, 129.6, 132.2. 19F
NMR d 275.8. IR (neat): 3152, 3002, 2925, 2225, 1606,
1491, 1442, 1409, 1355, 1305, 1209, 1178, 1056, 911, 755,
695 cm21. MS m/z 227 (2, Mþþ1), 226 (14, Mþ), 182
(100). Anal. calcd for C12H9F3O; C, 63.72; H, 4.01. Found:
C, 64.00; H, 4.26.
4.4.14. (3R p,4R p)-3,4-Epoxy-4-(hydroxyphenyl)methyl-
1-phenyl-3-trifluoromethyloct-1-yne (4m). Purified by
silica gel column chromatography (hexane/diethyl ether
10:1) followed by GPC. Yield: 82% of a 60:40 dia-
stereomeric mixture. Pale yellow oil. Rf 0.35 (hexane/ethyl
1
acetate 10:1). Major (3R p,4R p)-diastereomer: H NMR d
0.77 (t, J¼7.2 Hz, 3H), 0.92–1.28 (m, 3H), 1.39–1.55 (m,
1H), 1.65–1.88 (m, 1H), 1.93–2.08 (m, 1H), 2.40 (brs, 1H),
5.14 (s, 1H), 7.30–7.52 (m, 10H). 13C NMR d 13.7, 23.0,
27.4, 29.0, 58.8 (q, J¼40.2 Hz), 72.2 (q, J¼4.2 Hz), 73.2,
79.3, 89.0, 120.7, 122.6 (q, J¼277.9 Hz), 125.6, 127.9,
128.3, 128.5, 129.6, 132.0, 138.3. 19F NMR d 266.5. IR
(neat): 3449, 3065, 2961, 2934, 2874, 2235, 1603, 1493,
1452, 1381, 1325, 1246, 1182, 1055, 937, 841, 756, 731,
689 cm21. MS m/z 375 (0.1, Mþþ1), 374 (0.4, Mþ), 176
(90), 183 (45), 133 (100). Anal. calcd for C22H21F3O2: C,
70.58; H, 5.65. Found: C, 70.46; H, 5.62. Minor (3R p,4S p)-
diastereomer (only assignable peaks are shown): 1H NMR d
0.72 (t, J¼7.8 Hz, 3H), 2.41 (brs, 1H), 5.04 (s, 1H). 13C
NMR d 13.6, 22.8, 26.4, 29.0, 60.4 (q, J¼40.0 Hz), 72.7 (q,
J¼3.4 Hz), 71.4, 79.7, 88.7, 120.9, 122.7 (q, J¼278.0 Hz),
125.6, 128.0, 128.4, 128.5, 129.5, 132.0, 139.6. 19F NMR d
265.8.
4.4.10. (3R p,4S p)-3,4-Epoxy-1-phenyl-3-trifluoro-
methylhex-5-en-1-yne (4i). Yield: 67%. Colorless oil. Rf
0.50 (hexane/ethyl acetate 10:1). 1H NMR d 3.89 (d,
J¼7.0 Hz, 1H), 5.59–5.95 (m, 3H), 7.29–7.46 (m, 3H),
7.49–7.59 (m, 2H). 13C NMR d 55.2 (q, J¼40.6 Hz), 61.2,
78.7, 88.7, 120.6, 121.6 (q, J¼276.8 Hz), 124.8, 128.4,
129.7, 130.1, 132.1. 19F NMR d 275.9. IR (neat): 3061,
2928, 2241, 1491, 1445, 1356, 1298, 1221, 1182, 1153,
1130, 1009, 982, 957, 908, 756, 729, 689 cm21. MS m/z 240
(0.3, Mþþ2), 239 (4, Mþþ1), 238 (31, Mþ), 169 (48,
Mþ2CF3), 141 (100). Anal. calcd for C13H9F3O: C, 65.55;
H, 3.81. Found: C, 65.50; H, 4.09.
4.4.11. (3R p,4R p)-3,4-Epoxy-1-phenyl-3-trifluoro-
methyl-4-(trimethylsilyl)oct-1-yne (4j). Purified by silica
gel column chromatography (hexane/diethyl ether 10:1)
followed by GPC. Yield: 79%. Colorless oil. Rf 0.63
(hexane/ethyl acetate 10:1). 1H NMR d 0.24 (s, 9H), 0.94 (t,
J¼7.1 Hz, 3H), 1.31–1.71 (m, 5H), 2.05–2.17 (m, 1H),
7.29–7.40 (m, 3H), 7.44–7.51 (m, 2H). 13C NMR d 1.22 (q,
J¼2.7 Hz), 13.9, 23.0, 27.4, 36.2, 58.5 (q, J¼42.9 Hz), 65.3,
81.0, 86.7, 120.2, 123.0 (q, J¼276.6 Hz), 128.4, 129.3,
132.0. 19F NMR d 270.7. IR (neat): 3049, 2951, 2860,
2224, 1598, 1488, 1335, 1250, 1181, 1069, 1020, 908, 842,
755, 686 cm21. MS m/z 342 (0.3, Mþþ2), 341 (1, Mþþ1),
340 (5.0, Mþ), 271 (100, Mþ2CF3). Anal. calcd for
C18H23F3OSi: C, 63.50; H, 6.81. Found: C, 63.43; H, 6.76.
4.4.15. (3R p,4R p)-3,4-Epoxy-4-(diethylhydroxy)methyl-
1-phenyl-3-trifluoromethyloct-1-yne (4n). Purified by
silica gel column chromatography (hexane/diethyl ether
10:1) followed by GPC. Yield: 71%. Yellow oil. Rf 0.38
1
(hexane/ethyl acetate 10:1). H NMR d 0.93 (t, J¼7.0 Hz,
3H), 0.99 (t, J¼7.6 Hz, 6H), 1.23–1.57 (m, 5H), 1.64–
1.82 (m, 4H), 1.88 (brs, 1H), 2.05–2.28 (m, 1H), 7.24–
7.39 (m, 3H), 7.44–7.50 (m, 2H). 13C NMR d 7.45, 7.78,
13.9, 23.1, 27.3, 29.5, 30.8, 31.6, 58.5 (q, J¼42.1 Hz),
74.7, 76.8, 81.3, 89.1, 121.2, 123.1 (q, J¼277.4 Hz),
128.4, 129.4, 131.9. 19F NMR d 260.0. IR (neat): 3601,
2963, 2858, 1485, 1459, 1387, 1305, 1240, 1183, 1150,
1068, 1153, 1070, 1038, 911, 838, 746, 685 cm21. MS
m/z 356 (4, Mþþ2), 355 (23, Mþþ1), 354 (100, Mþ),
183 (89). Anal. calcd for C20H25F3O: C, 67.78; H, 7.11.
Found: C, 68.06; H, 7.00.
4.4.12. (3R p,4S p)-3,4-Epoxy-1-phenyl-3-trifluoro-
methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
oct-1-yne (4k). Yield: 62%. Pale yellow oil. Rf 0.38
1
(hexane/ethyl acetate 10:1). H NMR (500 MHz) d 0.93

M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
9819
4.4.16. (3R p,4R p)-3,4-Epoxy-4-(hydroxydiphenyl)-
methyl-1-phenyl-3-trifluoromethyloct-1-yne (4o). Puri-
fied by silica gel column chromatography (hexane/diethyl
ether 10:1) followed by GPC. Yield: 68% as colorless
crystals, mp 1278C. Rf 0.32 (hexane/ethyl acetate 10:1). 1H
NMR d 0.29–0.47 (m, 1H), 0.52 (t, J¼7.2 Hz, 3H), 0.79–
0.94 (m, 2H), 0.98–1.26 (m, 1H), 1.83 (dt, J¼12.6, 4.8 Hz,
1H), 2.26 (dt, J¼12.6, 4.8 Hz, 1H), 3.23 (brs, 1H), 7.24–
7.52 (m, 15H). 13C NMR d 13.5, 22.3, 26.0, 33.1, 60.4 (q,
J¼42.2 Hz), 75.6, 80.1 (q, J¼278.3 Hz), 80.7, 90.1, 120.9,
121.8 (q, J¼278.3 Hz), 127.8, 127.9, 128.05, 128.09 (2C),
128.2, 128.5, 129.6, 132.0, 140.8, 141.7. 19F NMR d 260.6.
IR (nujol): 3563, 2920, 2850, 2230, 1493, 1310, 1238, 1193,
1180, 960, 760, 698, 660 cm21. MS m/z 452 (0.1, Mþþ2),
451 (3, Mþþ1), 450 (10, Mþ), 393 (21, Mþ2Bu), 183
(100), 105 (80). Anal. calcd for C28H25F3O: C, 74.65; H,
5.59. Found: C, 74.85; H, 5.68.
quenching with saturated aqueous NH4Cl solution. Usual
workup and silica gel column chromatography (hexane/
diethyl ether 10: 1) followed by GPC gave 4r. Yield: 70%.
1
Pale yellow oil. Rf 0.50 (hexane/ethyl acetate 10:1). H
NMR d 0.93 (t, J¼7.1 Hz, 3H), 1.33–1.60 (m, 4H), 1.73–
2.07 (m, 2H), 2.48–2.70 (m, 2H), 5.20 (d, J¼11.2 Hz, 1H),
5.22 (d, J¼15.8 Hz, 1H), 5.73–5.94 (m, 1H), 7.29–7.39 (m,
3H), 7.42–7.49 (m, 2H). 13C NMR d 13.9, 22.7, 26.7, 34.0
(q, J¼3.1 Hz), 58.6 (q, J¼34.8 Hz), 69.7, 80.2, 87.9, 119.0,
121.1, 122.6 (q, J¼277.5 Hz), 128.4, 129.5, 131.9, 132.1.
19F NMR d 267.2. IR (neat): 3084, 2961, 2874, 2235, 1643,
1491, 1445, 1406, 1333, 1250, 1184, 1155, 1049, 924, 756,
727, 689 cm21. MS m/z 309 (0.2, Mþþ1), 308 (1, Mþ), 182
(100). Anal. calcd for C18H19F3O: C, 70.12; H, 6.21. Found:
C, 70.39; H, 6.22.
4.4.20. (3R p,4R p)-4-(Dimethylphenyl)silyl-3,4-epoxy-1-
phenyl-3-trifluoromethyloct-1-yne (4s). To a solution of
1c (280 mg, 1.0 mmol) in THF (5 mL) was added BuLi
(1.50 M, 2.0 mL, 3.0 mmol) at 2988C. The solution was
stirred at 2988C for 15 min. Iodomethane (93 mL,
1.5 mmol) in HMPA (1.0 mL, 6.0 mmol) were added to
the solution at 2988C and the resulting solution was
gradually warmed to 2788C over a period of 3 h before
quenching with aqueous saturated NH4Cl solution. Usual
workup followed purification on silica gel column chroma-
tography (hexane/diethyl ether 10:1) gave 4s (180 mg, 64%
yield). Colorless oil. Rf 0.58 (hexane/ethyl acetate 10:1). 1H
NMR d 0.46 (s, 3H), 0.52 (s, 3H), 0.71 (t, J¼7.2 Hz, 3H),
0.89–1.62 (m, 5H), 1.90 (dt, J¼12.2, 4.5 Hz, 1H), 7.29–
7.64 (m, 10H). 13C NMR d 22.78, 23.29, 13.5, 22.7, 26.8,
36.3, 58.7 (q, J¼41.0 Hz), 65.8, 80.9, 86.9, 121.2, 122.9 (q,
J¼277.0 Hz), 127.7, 128.4, 129.3, 129.5, 132.0, 134.2,
136.5. 19F NMR d 270.4. IR (neat): 30.61, 2950, 2859,
2221, 1483, 1419, 1332, 1252, 1180, 1162, 1098, 1071,
1118, 903, 810, 753, 693 cm21. MS m/z 404 (3, Mþþ2),
403 (11, Mþþ1), 402 (36, Mþ), 135 (100). Anal. Calcd for
C23H25F3OSi: C, 68.63; H, 6.26. Found: C, 68.49; H, 6.25.
4.4.17. (3R p,4R p)-3,4-Epoxy-4-(hydroxydiphenyl)-
methyl-1-phenyl-3-trifluoromethyloctane (4p). Purified
by silica gel column chromatography (hexane/diethyl
ether 10:1) followed by GPC. Yield: 57% as colorless
crystals, mp 1178C. Rf 0.30 (hexane/ethyl acetate 10:1). 1H
NMR d 0.11–0.22 (m, 1H), 0.52 (t, J¼7.0 Hz, 3H), 0.66–
0.98 (m, 4H), 1.79–1.96 (m, 2H), 2.23–2.38 (m, 1H), 2.96
(t, J¼9.6 Hz, 2H), 3.40 (brs, 1H), 7.18–7.45 (m, 15H). 13C
NMR d 13.4, 22.2, 26.5, 30.4, 31.4, 33.3, 66.2 (q,
J¼39.4 Hz), 73.2, 80.1, 124.1 (q, J¼281.5 Hz), 126.5,
127.6 (2C), 127.9, 128.0 (2C), 128.11, 128.13, 128.7, 140.7,
142.1. 19F NMR d 259.7. IR (nujol): 3568, 2924, 2855,
1493, 1305, 1259, 1173, 1155, 1107, 1043, 883, 772,
706 cm21. MS m/z 455 (0.1, Mþþ1), 454 (0.2, Mþ), 183
(100), 105 (85). Anal. calcd for C28H29F3O: C, 73.99; H,
6.43. Found: C, 74.09; H, 6.59.
4.4.18. (3R p,4R p)-3,4-Epoxy-4-(hydroxydiphenyl)-
methyl-1-phenyl-3-trifluoromethyloct-1-ene (4q). Puri-
fied by silica gel column chromatography (hexane/diethyl
ether 10:1) followed by GPC. Yield: 55% of a dia-
stereomeric mixture of 89: 11. Major (3R p,4R p)-isomer
was separated from the mixture in 46% yield as colorless
crystals, mp. 1248C. Rf 0.29 (hexane/ethyl acetate 10:1). 1H
NMR d 0.09–0.26 (m, 1H), 0.38 (t, J¼7.0 Hz, 3H), 0.48–
0.88 (m, 3H), 1.69 (dt, J¼10.8, 5.4 Hz, 2H), 3.47 (brs, 1H),
6.44 (d, J¼16.0 Hz, 1H), 6.84 (d, J¼16.0 Hz, 1H), 7.27–
7.48 (m, 15H). 13C NMR d 13.3, 22.2, 26.6, 31.2, 67.6 (q,
J¼37.2 Hz), 75.5, 79.9, 119.8, 123.3 (q, J¼280.0 Hz),
126.8, 127.6, 127.7 (2C), 127.9, 128.1, 128.3, 128.6, 128.8,
134.1, 142.7, 145.5. 19F NMR d 260.7. IR (nujol): 3574,
2924, 2852, 1493, 1448, 1254, 1190, 1146, 1115, 1086,
1026, 974, 914, 764, 752, 700, 665 cm21. MS m/z 454 (0.2,
Mþþ2) 453 (4, Mþþ1), 452 (13, Mþ), 252 (92), 183 (69),
105 (100). Anal. calcd for C28H27F3O: C, 74.32; H, 6.01.
Found: C, 74.08; H, 5.91.
4.4.21. (3R p,4R p)-3,4-Epoxy-4-methyl-1-phenyl-3-tri-
fluoromethyloct-1-yne (4s0). Yield: 77%. Colorless oil. Rf
0.58 (hexane/ethyl acetate 10:1). 1H NMR d 0.93 (t,
J¼7.0 Hz, 3H), 1.26–1.52 (m, 4H), 1.62 (s, 3H), 1.75–
1.86 (m, 2H), 7.28–7.42 (m, 3H), 7.47–7.53 (m, 2H). 13C
NMR d 13.8, 20.9, 22.7, 32.3 (q, J¼3.1 Hz), 58.6 (q,
J¼39.7 Hz), 68.3, 80.5, 87.8, 121.1, 122.7 (q, J¼277.4 Hz),
128.4, 129.4, 132.1. 19F NMR d 267.7. IR (neat): 3059,
2961, 2936, 2874, 2235, 1491, 1445, 1385, 1331, 1252,
1188, 1155, 1063, 1011, 922, 897, 756, 729, 691 cm21. MS
m/z 284 (0.2, Mþþ2), 283 (1, Mþþ1), 282 (7, Mþ), 267 (1,
Mþ2Me), 182 (100). Anal. calcd for C16H17F3O: C, 68.07;
H, 6.07. Found: C, 68.02; H, 6.04.
4.5. General procedure for the preparation of tetrasub-
stituted alkenes 8
4.4.19. (3R p,4R p)-3,4-Epoxy-4-(prop-1-en-3-yl)-1-phe-
nyl-3-trifluoromethyloct-1-yne (4r). To a solution of 1c
(1.0 mmol) in THF (5 mL) was added BuLi (3.0 mmol) at
2988C. The solution was stirred at 2988C for 15 min. Allyl
bromide (130 mL, 1.5 mmol) in hexamethylphosphoric
triamide (HMPA) (1.0 mL, 6 mmol) was added to the
solution at 2988C and the resulting solution was allowed to
warm gradually to 2788C over a period of 3 h before
To a solution of 1 (1.0 mmol) in THF (3 mL) was added
Grignard reagent R2MgBr (1.0 mmol) at 2788C. After
stirred at 2788C for 1 h, the solution was added R2Li
(3.0 mmol) at 2788C and was allowed to warm to room
temperature gradually before quenching with saturated
aqueous NH4Cl solution. The aqueous layer was extracted
with diethyl ether three times and the combined organic

9820
M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
layer was dried over anhydrous MgSO4 and concentrated in
vacuo. The crude residue was purified by column chroma-
tography on silica gel giving rise to 8.
4.5.6. 1,1,1-Trifluoro-3-methyl-2-phenylbut-2-ene (8f).
Yield: 69%. Colorless oil. Rf 0.68 (hexane/ethyl acetate
10:1). 1H NMR d 1.62 (q, J¼2.4 Hz, 3H), 2.07 (q,
J¼2.4 Hz, 3H), 7.13–7.17 (m, 2H), 7.32–7.42 (m, 3H).
19F NMR d 256.3 (t, J¼2.6 Hz). MS m/z 202 (0.8, Mþþ2),
201 (12, Mþþ1), 200 (100, Mþ), 185 (41). HRMS (EI) m/z
4.5.1. 2-Methyl-5-phenyl-3-trifluoromethylpet-2-ene
(8a). Yield: 60%. Colorless oil. Rf 0.63 (hexane/ethyl
1
acetate 10:1). H NMR d 1.63 (q, J¼2.2 Hz, 3H), 1.88 (q,
M
þ Calcd for C11H11F3, 200.0813; found, 200.0821.
J¼2.6 Hz, 3H), 2.47 (t, J¼8.6 Hz, 2H), 2.69 (m, 2H), 7.18–
7.36 (m, 5H). 13C NMR d 21.5, 21.6, 30.6 (q, J¼2.7 Hz),
35.3, 123.7 (q, J¼27.0 Hz), 125.2 (q, J¼274.3 Hz), 126.0,
128.4, 128.5, 141.3, 141.4. 19F NMR d 257.8. IR (neat):
3030, 2930, 1660, 1600, 1600, 1500, 1450, 1320, 1220,
1180, 1110, 1040, 750, 700 cm21. MS m/z 230 (0.2,
Mþþ2), 229 (3, Mþþ1), 228 (18, Mþ), 91 (100). HRMS
(EI) m/z Mþ calcd for C13H15F3, 228.1126; found,
228.1109. Anal. calcd for C13H15F3: C, 68.41; H, 6.62.
Found: C, 68.67; H, 6.90.
4.5.7. 3-Butyl-1,1,1-trifluoro-2-phenylhep-2-ene (8g).
Yield: 60%. Colorless oil. Rf 0.66 (hexane/ethyl acetate
10:1). 1H NMR d 0.73 (t, J¼7.2 Hz, 3H), 0.96 (t, J¼7.2 Hz,
3H), 1.00–1.53 (m, 8H), 1.88 (t, J¼6.8 Hz, 2H), 2.33–2.40
(m, 2H), 7.14–7.18 (m, 2H), 7.34–7.41 (m, 3H). 13C NMR
d 13.7, 13.9, 22.6, 23.0, 30.3, 31.1, 31.6, 33.3, 124.3 (q,
J¼274.0 Hz), 127.1 (q, J¼29.0 Hz), 127.6, 128.2, 130.0,
135.9, 152.0 (q, J¼2.7 Hz). 19F NMR d 256.0. IR (neat):
2960, 2870, 1640, 1460, 1330, 1240, 1150, 1110, 910, 760,
700 cm21. MS m/z 286 (0.7, Mþþ2), 285 (9, Mþþ1), 284
(5, Mþ), 172 (100). Anal. calcd for C17H23F3: C, 71.80; H,
8.15. Found: C, 71.98; H, 8.37.
4.5.2. 1-Phenyl-4-methyl-3-trifluoromethylpenta-1,3-
diene (8b). Yield: 15%. Colorless oil. Rf 0.50 (hexane/
ethyl acetate 10:1). 1H NMR d 2.00–2.07 (m, 6H), 6.59 (d,
J¼16.8 Hz, 1H), 6.70 (d, J¼16.8 Hz, 1H), 7.24–7.48 (m,
5H). 19F NMR d 256.9. IR (neat): 3020, 2920, 1640, 1600,
1490, 1440, 1340, 1220, 1110, 960, 750, 690 cm21. MS m/z
228 (0.4, Mþþ2), 227 (7, Mþþ1), 226 (50, Mþ), 211 (100).
HRMS (EI) m/z Mþ calcd for C13H13F3, 228.1126; found,
228.1109.
4.5.8. (E)-4-Methyl-1-phenyl-3-trifluoromethyloct-3-en-
1-yne (5a). Rf 0.60 (hexane/ethyl acetate 10: 1). 1H NMR d
0.96 (t, J¼7.0 Hz, 3H), 1.26–1.62 (m, 4H), 2.05 (q,
J¼2.2 Hz, 3H), 2.51 (dt, J¼7.7, 1.3 Hz, 2H), 7.29–7.34
(m, 3H), 7.39–7.48 (m, 2H). 13C NMR d 13.9, 19.1 (q,
J¼1.9 Hz), 22.5, 29.5 (q, J¼1.2 Hz), 38.17, 82.53 (q,
J¼3.7 Hz), 95.09, 111.5 (q, J¼33.9 Hz), 122.5 (q,
J¼272.9 Hz), 123.0, 128.3, 128.4, 131.3, 157.6. 19F NMR
d 258.5. IR (neat): 3050, 2950, 2850, 2200, 1615, 1595,
1485, 1440, 1350, 1255, 1225, 1120, 1080, 1010, 910, 750,
690 cm21. MS m/z 268 (3, Mþþ2), 267 (29, Mþþ1), 266
(100, Mþ), 251 (4, Mþ2Me), 197 (53, Mþ2CF3). Anal.
calcd for C16H17F3: C, 72.16; H, 6.43. Found: C, 72.22; H,
6.51.
4.5.3. 4-Butyl-1-phenyl-3-trifluoromethylocta-1,3-diene
(8c). Yield: 26%. Colorless oil. Rf 0.65 (hexane/ethyl
acetate 10:1). 1H NMR d 0.89–0.97 (m, 6H), 1.31–1.50 (m,
8H), 2.20–2.40 (m, 4H), 6.60 (d, J¼16.4 Hz, 1H), 6.73 (d,
J¼16.4 Hz, 1H), 7.26–7.46 (m, 5H). 13C NMR d 13.89,
13.93, 22.9, 23.1, 30.7, 31.1, 33.5, 34.0, 123.4 (q,
J¼28.0 Hz), 124.5 (q, J¼275.0 Hz), 126.3, 127.8, 128.7,
132.7, 137.3, 152.5. 19F NMR d 256.2. IR (neat): 2960,
2870, 1590, 1460, 1340, 1230, 1110, 960, 750, 690 cm21
.
4.5.9. (E)-4-Methyl-1-phenyl-3-trifluoromethyloct-3-en-
1-yne (5b). Rf 0.58 (hexane/ethyl acetate 10:1). 1H NMR d
0.95 (t, J¼7.0 Hz, 3H), 1.10 (t, J¼7.5 Hz, 3H), 1.36–1.62
(m, 4H), 2.38 (ddq, J¼7.5, 1.6, 1.6 Hz, 2H), 2.45–2.53 (m,
2H), 7.28–7.35 (m, 3H), 7.38–7.48 (m, 2H). 13C NMR d
12.9, 13.9, 22.9, 25.8 (q, J¼1.9 Hz), 30.0, 35.1, 82.8 (q,
J¼3.0 Hz), 95.2, 111.1 (q, J¼33.8 Hz), 122.5 (q,
J¼272.9 Hz), 123.0, 128.35, 128.41, 131.3, 163.4 (q,
J¼2.3 Hz). 19F NMR d 258.0. IR (neat): 3057, 2959,
2876, 2210, 1612, 1595, 1491, 1458, 1445, 1356, 1275,
1256, 1217, 1165, 1123, 1055, 999, 914, 754, 729,
689 cm21. MS m/z 282 (3, Mþþ2), 281 (26, Mþþ1), 280
(100, Mþ), 223 (38, Mþ2Bu), 251 (27, Mþ2Et), 211 (9,
Mþ2CF3). Anal. calcd for C16H17F3: C, 72.84; H, 6.83.
Found: C, 72.80; H, 6.90.
MS m/z 312 (2, Mþþ2), 311 (17, Mþþ1), 310 (78, Mþ),
197 (100). Anal. calcd for C19H25F3: C, 73.52; H, 8.12.
Found: C, 73.45; H, 8.24.
4.5.4. 4-Methyl-1-phenyl-3-trifluoromethylpent-3-en-1-
yne (8d). Yield: 55%. Colorless oil. Rf 0.63 (hexane/ethyl
1
acetate 10:1). H NMR d 2.08 (q, J¼2.2 Hz, 3H), 2.18 (q,
J¼2.2 Hz, 3H), 7.31–7.37 (m, 3H), 7.44–7.51 (m, 2H). 19F
NMR d 258.4. IR (neat): 3050, 2910, 2200, 1620, 1590,
1480, 1440, 1370, 1340, 1250, 1230, 1160, 1120, 1040, 890,
750 cm21. MS m/z 226 (0.8, Mþþ2), 225 (13, Mþþ1), 224
(100, Mþ), 155 (54). HRMS (EI) m/z Mþ calcd for
C13H11F3, 224.0813; found, 224.0802.
4.5.5. 4-Butyl-1-phenyl-3-trifluoromethyloct-3-en-1-yne
(8e). Yield: 71%. Colorless oil. Rf 0.59 (hexane/ethyl
acetate 10:1). 1H NMR d 0.90–0.99 (m, 6H), 1.32–1.63 (m,
8H), 2.36 (m, 2H), 2.49 (t, J¼7.2 Hz, 2H), 7.32–7.37 (m,
3H), 7.42–7.48 (m, 2H). 13C NMR d 13.77, 13.80, 22.9,
23.0, 30.0, 60.6, 32.5, 35.5, 82.8, 95.3, 11.3 (q, J¼33.5 Hz),
122.5 (q, J¼273.0 Hz), 123.0, 128.3, 128.4, 131.3, 162.3.
19F NMR d 257.8. IR (neat): 2960, 2870, 1610, 1590, 1490,
1460, 1350, 1260, 1160, 1120, 1060, 750, 690 cm21. MS m/
z 310 (2, Mþþ2), 309 (19, Mþþ1), 308 (94, Mþ), 196
(100). Anal. calcd for C19H23F3: C, 74.00; H, 7.52. Found:
C, 73.73; H, 7.58.
4.6. Typical procedure for the preparation of tetrasub-
stituted alkenes 5
To a solution of 1c (280 mg, 1.0 mmol) in THF (5 mL) was
added BuLi (1.50 M, 2.0 mL, 3.0 mmol) at 2988C. The
solution was stirred at 2988C for 15 min and then was
added PhCuCB(OCMe2)2 (460 mg, 2.0 mmol) at 2988C.
The resulting solution was gradually warmed to room
temperature and then refluxed for 4 h before quenching with
aqueous saturated NH4Cl solution. The aqueous layer was
extracted with diethyl ether three times. The combined

M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
9821
organic layer was dried over anhydrous MgSO4 and
concentrated in vacuo. The subsequent purification by
column chromatography on silica gel (hexane only) gave 5c
(260 mg, 74% yield).
4.6.5. (E)-2-(1-Butyl-4-phenyl-2-trifluoromethylbut-1-
en-3-ynyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6E,
R25Bu). Yield: 76%. Pale yellow oil. Rf 0.34 (hexane/
ethyl acetate 10:1). 1H NMR d 0.94 (t, J¼7.0 Hz, 3H), 1.31
(s, 12H), 1.35–1.62 (m, 4H), 2.57 (t, J¼6.8 Hz, 2H), 7.24–
7.36 (m, 3H), 7.42–7.49 (m, 2H). 13C NMR d 13.8, 22.6,
24.6, 30.2, 34.1, 81.5, 84.5, 96.9, 119.3 (q, J¼33.8 Hz),
122.2 (q, J¼271.9 Hz), 122.4, 128.3, 128.8, 131.6, 151.0.
19F NMR d 262.9. IR (neat): 2961, 2861, 2208, 1612, 1491,
1445, 1346, 1249, 1180, 1134, 1030, 962, 851, 756, 689,
665 cm21. MS m/z 380 (3, Mþþ2), 379 (25, Mþþ1), 378
(100, Mþ), 377 (23, Mþ21). Anal. calcd for C21H26BF3O2:
C, 66.68; H, 6.93. Found: C, 66.44; H, 6.96.
4.6.1. (Z)-1-Phenyl-4-phenylethynyl-3-trifluoromethyl-
oct-3-en-1-yne (5c). Pale yellow oil. Rf 0.58 (hexane/ethyl
1
acetate 10: 1). H NMR d 0.99 (t, J¼7.1 Hz, 3H), 1.42 (tq,
J¼7.2, 7.1 Hz, 2H), 1.74 (tt, J¼7.4, 7.2 Hz, 2H), 2.70 (t,
J¼7.4 Hz, 2H), 7.32–7.41 (m, 6H). 13C NMR d 13.9, 22.2,
30.0, 36.2, 82.6, 86.3, 101.7, 104.2, 118.5 (q, J¼33.4 Hz),
121.6 (q, J¼273.1 Hz), 122.4, 128.4 (2C), 129.1, 131.4
(2C), 131.9, 137.9. 19F NMR d 261.1. IR (neat): 3063,
2959, 2930, 2862, 2210, 2187, 1597, 1570, 1491, 1443,
1356, 1242, 1192, 1132, 1069, 914, 754, 689, 665 cm21
.
4.6.6. (E)-2-(1,4-Diphenyl-2-trifluoromethyl-but-1-en-3-
ynyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (6E,
R25Ph). Yield: 86%. Pale yellow oil. Rf 0.24 (hexane/
MS m/z 354 (4, Mþþ2), 353 (28, Mþþ1), 352 (100, Mþ),
241 (37, Mþ2PhCC). Anal. calcd for C23H19F3: C, 78.39;
H, 5.43. Found: C, 78.63; H, 5.36.
1
ethyl acetate 10:1). H NMR (500 MHz) d 1.29 (s, 12H),
7.24–7.40 (m, 8H), 7.58 (m, 2H). 13C NMR (125 MHz) d
24.6, 82.8, 84.8, 95.8, 119.2 (q, J¼33.5 Hz), 122.2, 123.5 (q,
J¼272.2 Hz), 128.1, 128.3 (2C), 128.6, 128.9, 131.6, 137.5,
147.7. 19F NMR d 263.1. IR (neat): 3058, 2981, 2931,
2208, 1737, 1602, 1490, 1444, 1373, 1340, 1253, 1217,
1137, 1068, 977, 850 cm21. MS m/z 400 (1, Mþþ2), 399 (7,
Mþþ1), 398 (28, Mþ), 298 (100). Anal. calcd for
C23H22BF3O2: C, 69.37; H, 5.57. Found: C, 69.63; H, 5.83.
4.6.2. (3Z,5E)-4-Butyl-1-phenyl-3-trifluoromethyldec-
3,5-dien-1-yne (5d). Yield: 56%. Pale yellow oil. Rf 0.60
1
(hexane/ethyl acetate 10:1). H NMR d 0.92 (t, J¼7.4 Hz,
3H), 0.96 (t, J¼7.0 Hz, 3H), 1.27–1.60 (m, 8H), 2.21 (t,
J¼7.8 Hz, 2H), 2.67 (t, J¼7.5 Hz, 2H), 6.17 (dt, J¼15.6,
7.8 Hz, 1H), 6.59 (d, J¼15.6 Hz, 1H), 7.28–7.34 (m, 3H),
7.39–7.50 (m, 2H). 13C NMR d 13.9, 14.0, 22.3, 23.0, 31.1,
31.3, 31.8, 33.3, 84.1, 98.3, 110.1 (q, J¼33.6 Hz), 122.5 (q,
J¼273.5 Hz), 123.1, 125.5, 128.4, 128.5, 131.3, 139.5,
154.0. 19F NMR d 256.0. IR (neat): 3063, 2961, 2934,
2874, 2203, 1784, 1684, 1597, 1491, 1469, 1350, 1242,
1171, 1126, 1069, 908, 756, 733, 689, 665 cm21. MS m/z
336 (0.2, Mþþ2), 335 (3, Mþþ1), 334 (14, Mþ), 236 (100).
HRMS (EI) m/z Mþ calcd for C21H25F3, 334.1908; found,
334.1877.
4.6.7. (Z)-2-(1-Butyl-4-phenyl-2-trifluoromethyl-but-1-
en-3-ynyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6Z,
R25Bu). Yield: 54%. Pale yellow oil. Rf 0.34 (hexane/
ethyl acetate 10:1). 1H NMR d 0.95 (t, J¼6.8 Hz, 3H), 1.32
(s, 12H), 1.17–1.63 (m, 4H), 2.41–2.59 (m, 2H), 7.29–7.34
(m, 2H), 7.43–7.48 (m, 3H). 13C NMR d 13.8, 22.7,24.7,
31.2, 31.6, (q, J¼1.5 Hz), 84.1, 84.4, 93.0, 120.0 (q,
J¼30.0 Hz), 121.6 (q, J¼276.0 Hz), 122.7, 128.3, 128.6,
131.5, 151.4. 19F NMR d 259.2. IR (neat): 2980, 2931,
2874, 2210, 1599, 1490, 1445, 1381, 1310, 1246, 1178,
1063, 964, 847, 756, 691, 667 cm21. MS m/z 380 (3,
Mþþ2), 379 (23, Mþþ1), 378 (100, Mþ), 377 (23, Mþ21).
HRMS (EI) m/z Mþ calcd for C21H26BF3O2, 378.1978;
found, 378.2009.
4.6.3. (Z)-1,4-Diphenyl-3-trifluoromethyloct-3-en-1-yne
(5e). Yield: 66% as colorless crystals, mp 678C. Rf 0.59
1
(hexane/ethyl acetate 10:1). H NMR d 0.89 (t, J¼7.0 Hz,
3H), 1.27–1.44 (m, 4H), 2.80 (t, J¼6.4 Hz, 2H), 7.10–
7.21 (m, 2H), 7.27–7.40 (m, 6H), 7.46–7.53 (m, 2H).
13C NMR d 13.9, 22.5, 29.2, 39.1, 82.7, 95.9, 112.2 (q,
J¼32.8 Hz), 121.9 (q, J¼273.1 Hz), 122.7, 127.0, 127.9,
128.0, 128.4, 128.8, 131.5, 138.8, 158.9. 19F NMR d
257.2. IR (nujol): 2926, 2858, 2210, 1589, 1572, 1489,
1445, 1344, 1231, 1182, 1096, 1070, 1011, 920, 779, 756,
706, 691, 646 cm21. MS m/z 330 (3, Mþþ2), 329 (22,
Mþþ1), 328 (100, Mþ), 271 (15, Mþ2Bu), 251 (15,
Mþ2Ph). HRMS (EI) Mþ calcd for C21H19F3, 328.1439;
found, 328.1471.
4.6.8. (Z)-2-(1,4-Diphenyl-2-trifluoromethyl-but-1-en-3-
ynyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (6Z,
R25Ph). Yield: 31%. Pale yellow oil. Rf 0.24 (hexane/
ethyl acetate 10:1). 1H NMR d 1.28 (s, 12H), 7.22–7.55 (m,
10H). 13C NMR d 24.4, 84.2, 84.8, 94.2, 120.1 (q,
J¼33.4 Hz), 121.1 (q, J¼275.7 Hz), 122.3, 127.1, 127.8,
128.1, 128.4, 129.0, 131.7, 136.9, 150.1. 19F NMR d 258.5.
MS m/z 400 (0.6, Mþþ2), 399 (4, Mþþ1), 398 (14, Mþ),
298 (100). Anal. calcd for C23H22BF3O2: C, 69.37; H, 5.57.
Found: C, 69.20; H, 5.45.
4.6.4. (E)-1-4-Diphenyl-3-trifluoromethyloct-3-en-1-yne
(5e0). Yield: 84%. Colorless oil. Rf 0.59 (hexane/ethyl
acetate 10:1). 1H NMR d 0.85 (t, J¼6.8 Hz, 3H), 1.21–1.34
(m, 4H), 2.64–2.80 (m, 2H), 7.09–7.58 (m, 10H). 13C NMR
d 13.7, 22.6, 30.4, 34.5, (q, J¼1.9 Hz), 93.8, 94.4 112.5 (q,
J¼33.6 Hz), 122.5 (q, J¼273.5 Hz), 122.7, 128.0, 128.2,
128.3, 128.4, 128.7, 131.2, 140.3, 159.7. 19F NMR d 258.0.
IR (neat): 3059, 2961, 2932, 2874, 2212, 1591, 1491, 1442,
1356, 1271, 1248, 1171, 1126, 1069, 914, 756, 691, 665,
646 cm21. MS m/z 330 (3, Mþþ2), 329 (25, Mþþ1), 328
(100, Mþ), 271 (14, Mþ2Bu), 251 (14, Mþ2Ph). HRMS
(EI) m/z Mþ calcd for C21H19F3, 328.1439; found,
328.1425.
4.6.9. (Z)-(1,4-Diphenyl-2-trifluoromethyl-but-1-en-3-
ynyl)-dimethyl-phenyl-silane (9). Yield: 14%. Pale yellow
oil. Rf 0.46 (hexane/ethyl acetate 10:1). 1H NMR d 0.33 (s,
3H), 0.34 (s, 3H), 6.96–7.04 (m, 3H), 7.17–7.38 (m, 10H),
7.48–7.56 (m, 2H). 13C NMR d 20.77, 0.85, 84.0, 98.3,
120.8 (q, J¼272.8 Hz), 122.2, 125.7 (q, J¼35.3 Hz), 126.5,
126.7, 127.68, 127.73, 128.0, 128.1, 128.8, 129.2, 131.6,
133.0, 133.8, 136.9, 139.8, 143.4. 19F NMR d 260.1. IR
(neat): 3069, 3053, 3022, 2956, 2204, 1596, 1489, 1427,
1338, 1249, 1168, 1132, 1066, 939, 813, 756, 700 cm21
.

9822
M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
MS m/z 408 (7, Mþþ2), 407 (27, Mþþ1), 406 (78, Mþ),
309 (100). HRMS (EI) m/z Mþ calcd for C25H21F3Si,
406.1365; found, 406.1362.
8. Crystallographic data (excluding structure factors) for the
structures of 4o, 4q and 5e have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication numbers CCDC 213201, CCDC 213202, and
CCDC 213203. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (fax: þ44-1223-336033 or e-mail: depos-
it@ccdc.cam.ac.uk). X-Ray analysis of 4p also disclosed that a
CF3 group and Ph2C(OH) in 4p were arranged cis.
Acknowledgements
This work was supported by a Grant-in-Aid for COE
Research on Elements Science, No. 12CE2005 from the
Ministry of Education, Culture, Sports, Science, and
Technology, Japan. Japan Society for the Promotion of
Science (JSPS) is highly acknowledged for the financial
support to T. H. as a predoctoral research student. We thank
the Central Glass Co. Ltd. for a generous gift of 3,3-
dichloro-1,1,1-trifluoropropan-2-one.
9. Trapping of oxiranyllithium with such an electrophile as D2O,
MeSiCl, MeI, aldehyde, or ketone was reported to proceed
with retention of configuration at the lithiated carbon. (a)
Eisch, J. J.; Galle, J. E. J. Organomet. Chem. 1988, 341,
293–313. (b) Molander, G. A.; Mautner, K. J. Org. Chem.
1989, 54, 4042–4050. (c) Eisch, J. J.; Galle, J. E. J. Org.
Chem. 1990, 55, 4835–4840. (d) Lohse, P.; Loner, H.; Acklin,
P.; Sternfeld, F.; Pfaltz, A. Tetrahedron Lett. 1991, 32,
615–618. (e) Capriati, V.; Florio, S.; Luisi, R.; Salomone, A.
Org. Lett. 2002, 4, 2445–2448.
References
10. Hiyama, T. Organofluorine Compounds—Chemistry and
Applications. Springer: Berlin, 2000; p 129.
1. Reviews on oxiranyl anions: (a) Satoh, T. Chem. Rev. 1996,
96, 3303–3325. (b) Mori, Y. Rev. Heteroatom Chem. 1997,
17, 183–211. (c) Hodgson, D. M.; Gras, E. Synthesis 2002,
1625–1642. See also: (d) Molander, G. A.; Mautner, K. Pure
Appl. Chem. 1990, 62, 707–712. (e) Doris, E.; Dechoux, L.;
Mioskowski, C. Synlett 1998, 337–343.
11. Molines, H.; Normant, J.-M.; Wakselman, C. Tetrahedron
Lett. 1974, 15, 951–954.
12. Preparation of Alkenes. A Practical Approach. Williams, J. M.
J., Ed.; Oxford University: Oxford, 1996.
13. Li: (a) Ref.1e. (b) Ukaji, Y.; Yoshida, A.; Fujisawa, T. Chem.
Lett. 1990, 157–160. (c) Santiago, B.; Lopez, C.; Soderquist,
J. A. Tetrahedron Lett. 1991, 32, 3457–3460. (d) Soderquist,
J. A.; Lopez, C. Tetrahedron Lett. 1991, 32, 6305–6306. (e)
Doris, E.; Dechoux, L.; Mioskowski, C. Tetrahedron Lett.
1994, 35, 7943–7946. Al, Zn: (f) Taniguchi, M.; Oshima, K.;
Utimoto, K. Tetrahedron Lett. 1991, 32, 2783–2786. (g)
Kasatkin, A. N.; Whitby, R. J. Tetrahedron Lett. 2000, 41,
6201–6205. Zr: (h) Kasatkin, A. N.; Whitby, R. J. Tetra-
hedron Lett. 2000, 41, 5275–5280. Ce: (i) Ukaji, Y.; Fujisawa,
T. Tetrahedron Lett. 1988, 29, 5165–5168.
2. (a) Concise reviews of rearrangement of b-oxido carbenoids:
Wovkulich, P. M. Comprehensive Organic Synthesis, Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 1, pp
873–877. (b) Boche, G.; Lohrenz, J. C. W. Chem. Rev. 2001,
101, 697–756. For pioneering works, see: (c) Villieras, J.;
Bacquet, C.; Normant, J. F. J. Organomet. Chem. 1972, 40,
¨
C1–C4. (d) Kobrich, G.; Grosser, J. Tetrahedron Lett. 1972,
13, 4117–4120. (e) Taguchi, H.; Yamamoto, H.; Nozaki, H.
¨
Tetrahedron Lett. 1972, 13, 4661–4662. (f) Kobrich, G.;
Grosser, J. Chem. Ber. 1973, 106, 2626–2635. (g) Villieras, J.;
Bacquet, C.; Normant, J. F. J. Organomet. Chem. 1975, 97,
325–354. (h) Taguchi, H.; Yamamoto, H.; Nozaki, H. Bull.
Chem. Soc. Jpn. 1977, 50, 1592–1595.
14. The results contrast sharply to the previous examples. Ref.
13b–e.
15. The reactivities of 3 towards organoaluminum, -zinc, and
-boranes contrast to that of oxiranyllithium generated from
triphenylsilyloxirane. Ref. 13f.
¨
3. Kobrich and Grosser postulated oxiranyllithiums as inter-
mediates in the reaction of Ph2C(OLi)CLiCl2 with ArLi but
they could not detect the oxiranyllithiums by usual trapping
reaction. See Ref. 2f.
16. (a) Hata, T.; Kitagawa, H.; Masai, H.; Kurahashi, T.; Shimizu,
M.; Hiyama, T. Angew. Chem., Int. Ed. 2001, 40, 790–792. (b)
Shimizu, M.; Kitagawa, H.; Kurahashi, T.; Hiyama, T. Angew.
Chem., Int. Ed. 2001, 40, 4283–4286. (c) Shimizu, M.;
Kurahashi, T.; Hiyama, T. Synlett 2001, 1006–1008. (d)
Kurahashi, T.; Hata, T.; Masai, H.; Kitagawa, H.; Shimizu, M.;
Hiyama, T. Tetrahedron 2002, 58, 6381–6395. (e) Shimizu,
M.; Kurahashi, T.; Kitagawa, H.; Hiyama, T. Org. Lett. 2002,
5, 225–227.
4. (a) Hata, T.; Shimizu, M.; Hiyama, T. Synlett 1996, 831–832.
(b) Shimizu, M.; Takebe, Y.; Kuroboshi, M.; Hiyama, T.
Tetrahedron Lett. 1996, 37, 7387–7390. (c) Shimizu, M.;
Hata, T.; Hiyama, T. Tetrahedron Lett. 1997, 38, 4591–4594.
(d) Shimizu, M.; Yamada, N.; Takebe, Y.; Hata, T.;
Kuroboshi, M.; Hiyama, T. Bull. Chem. Soc. Jpn. 1998, 71,
2903–2921. (e) Shimizu, M.; Hata, T.; Hiyama, T. Tetra-
hedron Lett. 1999, 40, 7375–7378. (f) Hata, T.; Kitagawa, H.;
Shimizu, M.; Hiyama, T. Bull. Chem. Soc. Jpn. 2000, 73,
1691–1695. (g) Shimizu, M.; Hata, T.; Hiyama, T. Hetero-
cycles 2000, 52, 707–717. (h) Shimizu, M.; Hata, T.; Hiyama,
T. Bull. Chem. Soc. Jpn. 2000, 73, 1685–1690.
17. (a) Rathke, M. W.; Kow, R. J. Am. Chem. Soc. 1972, 94,
6854–6856. (b) Matteson, D. S. Synthesis 1975, 147–158.
18. Review of Peterson olefination. Ager, D. J. Organic Reactions,
Wiley: New York, 1990; Vol. 38. pp 1–223.
19. (a) In Fluorine-containing molecules: Structure, Reactivity,
Synthesis, and Applications. Liebman, J. F., Greenberg, A.,
W. R. Dolbier, J., Eds.; VCH: New York, 1988. (b) In
Organofluorine Chemistry: Principles and Commercial Appli-
cations. Banks, R. E., Smart, B. E., Tatlow, J. C., Eds.;
Plenum: New York, 1994. (c) In Chemistry of Organic
Fluorine Compounds II A Critical Review. ACS Monograph
187, Hudlicky, M., Pavlath, A. E., Eds.; American Chemical
Society: Washington, DC, 1995. (d) In Organofluorine
5. Preliminary communication: Shimizu, M.; Fujimoto, T.;
Minezaki, H.; Hata, T.; Hiyama, T. J. Am. Chem. Soc. 2001,
123, 6947–6948.
6. Generation and reaction of a-trifluoromethyl oxiranyllithiums
is reported Yamauchi, Y.; Katagiri, T.; Uneyama, K. Org. Lett.
2002, 4, 173–176.
7. In the absence of HMPA, alkylation resulted in the low to
moderate yield of either 4s or 4s0.

M. Shimizu et al. / Tetrahedron 59 (2003) 9811–9823
9823
Chemistry: Fluorinated Alkenes and Reactive Intermediates.
Topics in Current Chemistry, Chambers, R. D., Ed.; Springer:
Berlin, 1997; Vol. 192. (e) In Organofluorine Chemistry:
Techniques and Synthons. Topics in Current Chemistry,
Chambers, R. D., Ed.; Springer: Berlin, 1997; Vol. 193. (f)
Begue, J.-P.; Bonnet-Delpon, D. Tetrahedron 1991, 47,
3207–3258. (g) McClinton, M. A.; McClinton, D. A. Tetra-
hedron 1992, 48, 6555–6666. (h) Ref. 10.