Highly Stereoselective Synthesis of Trifluoromethylated Compounds via Ester-Enolate [2,3]-Wittig and [3,3]-Ireland-Claisen Rearrangements

Article abstract of DOI:10.1021/jo961246i

γ-Trifluoromethylated propargylic alcohols have been obtained in optically pure forms via effective enzymatic kinetic resolution and then converted into (E)- or (Z)-allylic alcohols. [2,3]-Wittig rearrangement of the corresponding [[γ-(trifluoromethyl)allyl]oxy]acetic acid methyl esters afforded α-hydroxy-β-(trifluoromethyl)-γ,σ-unsaturated carboxylic acid methyl esters in good yields. The rearrangement of (Z)-substrates proceeded in a highly stereoselective manner to give anti-isomers with E configuration at a newly created olefinic bond via complete chirality transfer. (E)-Substrates, however, showed relatively low stereoselectivities resulting in mixtures of syn- and anti-products. The trifluoromethylated allylic alcohols were also converted into the corresponding α-methoxyacetic acid γ-(trifluoromethyl)allyl esters and evaluated as substrates for [3,3]-Ireland-Claisen rearrangement. (E)-Substrates were efficiently transformed into syn-products while (Z)-substrates exhibited relatively low stereoselectivities. The two complementary methods provide facile routes to highly functionalized trifluoromethyl-containing molecules with a high degree of stereocontrol.

Full text of DOI:10.1021/jo961246i

J . Org. Chem. 1997, 62, 137-150
137
High ly Ster eoselective Syn th esis of Tr iflu or om eth yla ted
Com p ou n d s via Ester -En ola te [2,3]-Wittig a n d
[3,3]-Ir ela n d -Cla isen Rea r r a n gem en ts
Tsutomu Konno, Hideki Umetani, and Tomoya Kitazume*
Department of Bioengineering, Tokyo Institute of Technology,
Nagatsuta, Midori-ku, Yokohama, 226, J apan
Received J uly 2, 1996X
γ-Trifluoromethylated propargylic alcohols have been obtained in optically pure forms via effective
enzymatic kinetic resolution and then converted into (E)- or (Z)-allylic alcohols. [2,3]-Wittig
rearrangement of the corresponding [[γ-(trifluoromethyl)allyl]oxy]acetic acid methyl esters afforded
R-hydroxy-â-(trifluoromethyl)-γ,δ-unsaturated carboxylic acid methyl esters in good yields. The
rearrangement of (Z)-substrates proceeded in a highly stereoselective manner to give anti-isomers
with E configuration at a newly created olefinic bond via complete chirality transfer. (E)-Substrates,
however, showed relatively low stereoselectivities resulting in mixtures of syn- and anti-products.
The trifluoromethylated allylic alcohols were also converted into the corresponding R-methoxyacetic
acid γ-(trifluoromethyl)allyl esters and evaluated as substrates for [3,3]-Ireland-Claisen rear-
rangement. (E)-Substrates were efficiently transformed into syn-products while (Z)-substrates
exhibited relatively low stereoselectivities. The two complementary methods provide facile routes
to highly functionalized trifluoromethyl-containing molecules with a high degree of stereocontrol.
Trifluoromethyl substitution on organic molecules
often confers significant changes in their chemical and
physical properties, and therefore CF3-containing materi-
als have received considerable attention in recent years.1
There are some established methods for the construction
of single chiral centers with a CF3 group,2-7 while, to date,
compounds with two contiguous stereocenters such as 1
(Scheme 1) are much more difficult to prepare both in
diastereo- as well as in enantioselective manners.8 It
might be that application of such stereoselective reactions
for nonfluorinated systems as the aldol reaction,9 Diels-
Alder reaction,10 and ene reaction11 would open new
routes to our target compounds, even though this is not
always reliable for fluorine-containing molecules. For
example, R-CF3-enolate 212 and R-CF3 aldehyde 3,13 which
might be utilized in an aldol reaction as a nucleophile
and an electrophile, respectively, are found to be difficult
to handle due to defluorination and/or epimerization.
Moreover, 2 is less nucleophilic than its nonfluorinated
counterpart, presumably due to the electron deficiency
of the carbon-carbon double bond due to the electron-
withdrawing (CF3) group (Scheme 1).
X Abstract published in Advance ACS Abstracts, December 15, 1996.
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Sigmatropic rearrangement has become a powerful tool
for the stereoselective construction of a new carbon-
carbon bond.14 In particular, [2,3]-Wittig15 and [3,3]-
Ireland-Claisen shifts16 (eqs 1 and 2 in Scheme 2,
respectively) have become indispensable synthetic meth-
ods because of their mild reaction conditions as well as
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S0022-3263(96)01246-7 CCC: $14.00 © 1997 American Chemical Society

138 J . Org. Chem., Vol. 62, No. 1, 1997
Konno et al.
Sch em e 1
(2) X ) an alkoxy group, R1 ) CF3. However, the former
is not a good choice because it involves the formation of
R-CF3 enolate12 which, as described above, can easily
undergo defluorination. The latter is therefore the
substrate of choice. Moreover, employment of chiral
secondary allylic alcohols in both reactions might result
in the formation of desired chiral materials possessing
two consecutive asymmetric centers with a hydroxyl (or
equivalent) and a CF3 group via [1,3]-chirality transfer.
Herein, we describe the scope and limitations of the ester
enolate [2,3]-Wittig variant of [[γ-(trifluoromethyl)allyl]-
oxy]acetate derivatives and the [3,3]-Ireland-Claisen
variant of R-methoxyacetic acid γ-(trifluoromethyl)allyl
esters in detail, placing emphasis on the development of
a new synthetic method for the construction of 1.
Sch em e 2
Resu lts a n d Discu ssion
P r ep a r a tion of Su bstr a tes for Ester -En ola te [2,3]-
Wittig Rea r r a n gem en t. Prior to the investigation of
sigmatropic rearrangements, both reaction paths in eqs
1 and 2 (Scheme 2) require γ-trifluoromethylated allylic
alcohols of specific stereochemistry. Thus, γ-trifluoro-
methylated propargylic alcohols18 were chosen as starting
materials because of their easy stereoselective transfor-
mation to both (E)- and (Z)-allylic alcohols. Furthermore,
enzymatic kinetic resolution was selected for the induc-
tion of chirality based on its convenience and simulta-
neous obtention of both enantiomers. After several
explorations of reaction conditions using rac-4a which
was prepared according to the literature,18f we found that
lipase (Novozym 435; Candida antarctica, immobilized)
in hexane with vinyl acetate preferentially acetylates S
alcohol (E value g 100). Thus, this system allowed us
to obtain the unreacted chiral alcohol, (R)-4a , with the
R configuration (>99% ee, 45% yield) with 52% conver-
sion. In this reaction, (S)-5a with 86% ee (47% yield)
was also isolated, which was resolved by further enzy-
matic esterification using the same conditions (>99% ee,
85% yield). The absolute configuration of (S)-5a was
assigned by its conversion into known diacetate (R)-6,
followed by comparison of optical rotation values19 (Scheme
3). On the other hand, (R)-4b (99% ee) in Scheme 4 was
synthesized by the literature method.17e,f We have also
attempted the enzymatic resolution of rac-4c by Lipase
PL (Alcaligenes sp.; Meito Sangyo Co., Ltd., J apan),
effectively affording (S)-alcohol (>99% ee, 45% yield) and
(R)-acetate (81% ee, 51% yield) at 56% conversion (E
value ) 78).20 The obtained chiral materials, along with
racemic propargylic alcohols, were converted into the
corresponding allylic alcohols by the method described
in the literature,18f followed by etherification with bro-
the predictable stereochemistry of the products. How-
ever, there are surprisingly few applications of these
processes to CF3-containing compounds,17 possibly for the
following reason.
If we apply the above rearrangements to the construc-
tion of 1, we might encounter several difficulties. In the
[2,3]-Wittig variant, allyl propargyl ether (G: CHtC) and
bisallyl ether (G: CH2dCH) would be suitable substrates
for our purpose (see eq 1 in Scheme 2) due to the high
stereoselection in the nonfluorinated counterpart; how-
ever, there exists the following possible problem. Con-
sidering the high electron-withdrawing ability of a CF3
group when introduced as R1, proton abstraction by a
strong base such as n-BuLi will proceed at the 1 position
preferentially, causing the formation of a difluorodiene
via the elimination of fluoride. Increasing the proton’s
acidity at the 1′ position would prevent this and might
be realized by using an ester group as a migrating
terminus. Thus the ester enolate [2,3]-Wittig rearrange-
ment should be suitable. In the [3,3]-Ireland-Claisen
rearrangement, on the other hand, the following two
modes can be considered for the preparation of our
desired compounds; (1) X ) CF3, R1 ) an alkoxy group,
(14) (a) Lutz, R. P. Chem. Rev. 1984, 84, 206. (b) Overman, L. E.
Angew. Chem., Int. Ed. Engl. 1984, 23, 579. (c) Ziegler, F. E. Chem.
Rev. 1988, 88, 1423. (d) Bennett, G. B. Synthesis 1977, 589. (e) Ziegler,
F. E. Acc. Chem. Res. 1977, 10, 227.
(15) (a) Nakai, T.; Mikami, K. Org. React. 1994, 46, 105. (b)
Marshall, J . A. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, Chapter 3. (c)
Nakai, T.; Mikami, K. Chem. Rev. 1986, 86, 885. (d) Mikami, K.;
Nakai, T. Synthesis 1991, 594. (e) Bru¨ckner, R. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,
1991; Vol 4, Chapter 4.6. (f) Nakai, T.; Mikami, K.; Sayo, N. J . Synth.
Org. Chem. J pn. 1983, 41, 100. (g) Hoffmann, R. W. Angew. Chem.,
Int. Ed. Engl. 1979, 18, 563.
(16) (a) Pereira, S.; Srebnik, M. Aldrichim. Acta 1993, 26, 17. (b)
Wipf, P. In Comprehensive Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Oxford, 1991; Vol. 7, Chapter 7.2. (c) Ireland, R. E.; Norbeck,
D. W.; Mandel, G. S.; Mandel, N. S. J . Am. Chem. Soc. 1985, 107, 3285.
(d) Ireland, R. E.; Thaisrivongs, S.; Wilcox, C. S. J . Am. Chem. Soc.
1980, 102, 1155. (e) Rowley, M.; Tsukamoto, M.; Kishi, Y. J . Am.
Chem. Soc. 1989, 111, 2735. (f) Abelman, M. M.; Funk, R. L.; Munger,
J . D., J r. J . Am. Chem. Soc. 1982, 104, 4030.
(17) There have been several reports concerning sigmatropic rear-
rangement of CF3-containing molecules. (a) Hanzawa, Y.; Kawagoe,
K.; Yamada, A.; Kobayashi, Y. Tetrahedron Lett. 1985, 26, 219. (b)
see ref 12b.
(18) Propargyl alcohols with a CF3 group have been synthesized from
3,3,3-trifluoropropyne. (a) Drakesmith, F. G.; Stewart, O. J .; Tarrant,
P. J . Org. Chem. 1968, 33, 280. (b) Sibous, L.; Tipping, A. E. J .
Fluorine Chem. 1993, 62, 39. (c) Ishihara, T.; Yamasaki, Y.; Ando, T.
Tetrahedron Lett. 1985, 26, 79. (d) Burton, D. J .; Yang, Z.-Y.; Morken,
P. A. Tetrahedron 1994, 50, 2993. Recently, we have reported the
convenient as well as reliable method for the preparation of γ-trifluo-
romethylated propargylic alcohol. (e) Mizutani, K.; Yamazaki, T.;
Kitazume, T. J . Chem. Soc., Chem. Commun. 1995, 51. (f) Yamazaki,
T.; Mizutani, K.; Kitazume, T. J . Org. Chem. 1995, 60, 6046.
(19) Herradon, B.; Cueto, S.; Morcuende, A.; Valverde, S. Tetrahe-
dron: Asym. 1993, 4, 845.
(20) The absolute configurations of (S)-4c was determined by its
transformation into (2S)-hexane-1,2-diol. (1. Lindlar cat./H2. 2. AcCl,
Py. 3. O3, then (CH3)2S. 4. NaBH4/EtOH. 5. K2CO3/MeOH) and
comparison of optical rotation value of subsequent diol to an authentic
value. Hasegawa, J .; Ogura, M.; Tsuda, S.; Maemoto, S.; Kutsuki, H.;
Ohashi, T. Agric. Biol. Chem. 1990, 54, 1819.

Stereoselective Synthesis of Trifluoromethylated Compounds
J . Org. Chem., Vol. 62, No. 1, 1997 139
Ta ble 1. [2,3]-Wittig Rea r r a n gem en t of (S)-(Z)-8ca
Sch em e 3a
entry
LDA (equiv)
additive
time (h)
yield (%)b,c
1
2
3
4
5
6
2
2
2
4
2
1.2
-
3
3
3
3
9
5 (87)d
80 (12)
3 (68)
HMPA
TMEDA
HMPA
HMPA
HMPA
62 (18)
77 (6)
<0.2
64e (trace)
a
b
All reactions were performed at -78 °C. Determined by 19F
NMR. c Unless otherwise noted, in the parentheses, the combined
yield of unknown compounds and recovered substrate was shown.
The yield of the recovered substrate in the parentheses. e Isolated
d
yield.
doubly activated by a CF3 group and a substituent R. This
might be due to decomposition via sequential abstraction
of the allylic hydrogen by NaH and elimination of fluoride
in the etherification step.
In vestigation of [2,3]-Wittig Rear r an gem en t. With
chiral substrates 8 in hand, we began to explore reaction
conditions for the [2,3]-Wittig rearrangement. LDA was
selected as a representative base and the reaction was
performed with (S)-(Z)-8c at -78 °C in THF. As shown
in Table 1, it was confirmed that the reaction does not
proceed without HMPA and we recovered the starting
material quantitatively (87% yield) (entry 1).21 HMPA
was the additive of choice rather than TMEDA (entry 2
vs 3). Employment of more than 2 equiv of LDA
increased the amount of unknown products (entry 4),
which might be difluorinated compounds because their
19F NMR peaks appeared in the range of 80-85 ppm
when hexafluorobenzene was used as an internal stan-
dard. On the other hand, the yield was independent of
the reaction time (entry 2 vs 5). The order of addition
made no difference; addition of the substrate into the
mixture of LDA/HMPA/THF and the addition of LDA into
the mixture of substrate/HMPA/THF gave the same
result. After all, it was revealed that subjection of (Z)-
R-(allyloxy)acetate (S)-(Z)-8c to 1.2 equiv of LDA in THF
at -78 °C in the presence of HMPA as a cosolvent
resulted in the rapid (<10 min) formation of R-hydroxy-
â-(trifluoromethyl)-γ,δ-unsaturated ester anti-9c in 64%
chemical yield, as the sole detectable isomer (entry 6).
Moreover, in this case, the suppression of side products
was observed. The obtained material was converted into
the corresponding diol, followed by esterification using
2 equiv of MTPA-Cl. The 19F NMR spectrum of this
MTPA ester showed only one set of peaks (one doublet
and two singlets), while in the racemic counterpart, two
sets of peaks were observed in a ratio of 1:1, strongly
suggesting that the rearranged product was in an opti-
cally pure form and that [1,3]-chirality transfer had
occurred completely.
Sch em e 4a
Under the same conditions, compounds 8a -e were
transformed into 9a -e, respectively. The results are
summarized in Table 2. As depicted in Table 2, no
dependence of the stereoselectivity on the side chain R
was observed for the anti isomers. Thus, when Z isomer
was employed as a substrate, anti selectivity was not
influenced by differences in the bulkiness of side chain
R (entry 5 vs 6, 7) or by the existence or position of an
oxygen atom in R which might coordinate to metal species
(entries 1 and 2). A [2,3]-Wittig shift in (Z)-substrates
moacetic acid and esterification, giving substrates in high
overall yields (Scheme 4).
Compounds (R ) phenyl, furyl, (E)-PhCHdCH) could
not be prepared such that the allylic hydrogen could be
(21) It has been reported that the ester enolate [2,3]-Wittig rear-
rangement proceeded smoothly in the presence of HMPA. (a) Taka-
hashi, O.; Sayo, T.; Mikami, K.; Nakai, T. Chem. Lett. 1986, 1599. (b)
Takahashi, O.; Maeda, T.; Mikami, K.; Nakai, T. Chem. Lett. 1986,
1355.

140 J . Org. Chem., Vol. 62, No. 1, 1997
Konno et al.
Ta ble 2. [2,3]-Wittig Rea r r a n gem en t
resulted in exclusive E selection at the newly created
olefinic bond. In addition, complete transfer of chirality
was achieved to obtain highly functionalized trifluoro-
methylated materials in enantiomerically pure forms. On
the other hand, (E)-8a and 8b rearranged to give syn
isomers with lower diastereoselectivity (syn:anti ) ca.
6:1). It should be noted that a large influence of the
substituent R upon the olefinic configuration was ob-
served, relative to the case of Z isomers, and that the
syn isomer consisted of E and Z forms in a ratio of 4:1-
1:1 (entry 3 vs 4). Generally, it has been reported that
enolate [2,3]-Wittig rearrangement in the nonfluorinated
system required several hours or more, and that the
reaction sometimes was completely only with a raising
of temperature.22 In sharp contrast, the [2,3]-Wittig
variant of 8 finished within 10 min even at -78 °C. The
driving force for the accelerated rearrangement is prob-
ably the decrease of the LUMO energy level of the allylic
portion due to the introduction of an electron-withdraw-
ing (CF3) group.23
ester-enolate [2,3]-Wittig rearrangement for the construc-
tion of our target structure 1 with a high degree of anti
selectivity, from starting propargylic alcohols in only
three steps. On the other hand, the corresponding syn
isomers were obtained in about 70% de, which left a
problem to be solved.
Exa m in a tion of [3,3]-Ir ela n d -Cla isen Rea r r a n ge-
m en t. Next, we examined [3,3]-Ireland-Claisen rear-
rangement as an alternative approach to our target
(22) There have been reported the following reaction conditions. (a)
(-78 °C, 22 h) Ender, D.; Backhaus, D.; Runsink, J . Angew. Chem.,
Int. Ed. Engl. 1994, 33, 2098. (b) (-70 °C, 10 h then -70 f 0 °C)
Takahashi, O.; Mikami, K.; Nakai, T. Chem. Lett. 1987, 69. (c) (-35
°C, 2 d) Reetz, M. T.; Griebenow, N.; Goddard, R. J . Chem. Soc., Chem.
Commun. 1995, 1605. (d) (-78 °C, 40 min, then -40 °C, 2.7 h)
Bru¨ckner, R. Chem. Ber. 1989, 122, 703. (e) (-78 °C, 2 h) Yokomatsu,
T.; Yamagishi, T.; Shibuya, S. Synlett 1995, 1035. (f) See ref 21.
(23) There have been some reports concerning an enhancement of
the reaction rate and/or the reactivity due to the introduction of a CF3
substituent. (a) Gassman, P. G.; Harrington, C. K. J . Org. Chem. 1990,
55, 1813. (b) Creary, X.; Sky, A. E.; Mehrsheikh-Mohammadi, M. E.
Tetrahedron Lett. 1988, 29, 6839. (c) Yamazaki, T.; Hiraoka, S.;
Kitazume, T. J . Org. Chem. 1994, 59, 5100.
As described above, we have proved the utility of the

Stereoselective Synthesis of Trifluoromethylated Compounds
J . Org. Chem., Vol. 62, No. 1, 1997 141
Sch em e 5a
while the reverse phenomenon was observed in the [2,3]-
Wittig rearrangement. Furthermore, the stereoselection
at the newly created olefinic bond was slightly affected
by the bulkiness of side chain R, and E:Z ) 93:7 was
obtained for R ) cyclohexyl, which is considered to be
the bulkiest substituent of those in Table 4 (entry 8). On
the other hand, the diastereomeric excesses of anti
isomers were a little lower than those of [2,3]-Wittig-
rearranged products derived from (Z)-substrates.
As depicted in the previous section on the [2,3]-Wittig
rearrangement, a similar phenomenon was observed for
the reaction rate. Generally, it is known that the
rearrangement is almost completed by heating the reac-
tion mixture (50-80 °C), although Koreeda et al. have
reported that an “anionic oxy-Ireland-Claisen shift”, in
which lithium enolate was not trapped by silyl species,
was completed even at very low temperature due to an
increase in the vinylic HOMO energy level.24 In our
system, the reaction might proceed efficiently even at
room temperature because of the decrease of the LUMO
energy level in the allylic group derived from a CF3
moiety.
Ta ble 3. Op tim iza tion of [3,3]-Ir ela n d -Cla isen
Rea r r a n gem en t of (S)-(Z)-10c
diastereoselectivity
yield
(%)c
entrya
base
LDA
methodb
(anti (E:Z):syn)c
1
2
3
A
B
A
B
B
96 (95:5):4
87 (91:9):13
93:7
96:4
98 (74:26):2
73
49
quant
quant
64
LDA
LHMDS
LHMDS
LHMDS
4
Cla r ifica tion of th e Ster eoch em istr y. The relative
stereochemistry was determined as outlined in Scheme
6. The stereostructure of anti-9c was confirmed after its
conversion to cyclic acetal 13. Thus, anti-9c was trans-
formed into alcohol 12 by the method described in
Scheme 6. Ozonolysis of 12 and the following reduction
furnished the corresponding diol, which was treated with
dimethoxypropane and a catalytic amount of PPTS to
give acetonide 13. Careful analysis of the 1H NMR
spectrum of 13 established the vicinal coupling constant
between Ha and Hb to be 9.83 Hz, strongly suggesting
its anti relative stereochemistry.
5d
a
All reaction mixture was stirred at -78 °C for 30 min after
the addition of substrate and TMSCl and was allowed to warm to
b
room temperature. Method A: TMSCl was added after the
addition of the substrate. Method B: TMSCl was added prior to
the addition of the substrate. c Determined by 19F NMR using C6F6
d
as an internal standard. TBSCl was employed instead of TMSCl.
molecule. The preparation of substrates for the [3,3]-
variant was accomplished by the usual esterification of
allylic alcohols with methoxyacetyl chloride (Scheme 5).
First of all, the influence of the base and silyl species
used for trapping lithium enolates was investigated by
using (S)-(Z)-10c.
On the other hand, methylation of an R-hydroxyl group
of anti-9a -e with Ag2O/MeI was followed by reduction
to give anti-11a -e, whose spectral data (except for 11e)
were consistent with those of the alcohols obtained via
[3,3]-Ireland-Claisen rearrangement of (Z)-isomers 10a -
d . Ozonolysis of anti-11a -e and the reduction of the
resultant aldehydes furnished the same materials 14,
indicating that the relative stereochemistry of [2,3]-
Wittig- and [3,3]-Claisen-rearranged products derived
from Z substrates was the same, i.e. anti. Furthermore,
the chiral compounds possess the same absolute config-
uration by comparison of their optical rotation values.
Employment of LHMDS instead of LDA as a base
increased the chemical yield (entry 1 vs 3 and entry 2 vs
4 in Table 3). When TMSCl was dropped into the enolate
solution with LHMDS, a slight decrease in the stereose-
lectivity was observed relative to the internal trap
method (entry 3 vs 4). On the other hand, a large
decrease in both the selectivity and chemical yield was
seen when substrate was added into the mixture of LDA
and TMSCl. Moreover, the anti isomer with the E
configuration at the newly created olefinic bond was
obtained as a sole stereoisomer when using LHMDS as
a base (entry 3 and 4), while anti isomer consisting of E
and Z forms was produced when LDA was used (entry 1
and 2). It should be noted that treatment of lithium
enolate with TBSCl instead of TMSCl resulted in de-
creasing stereoselectivity at the olefinic bond and yield,
although a slight increase in the relative stereoselectivity
was observed (entry 5). The best result was obtained
when the substrate was added to the mixture of LHMDS
and TMSCl, which was then stirred at -78 °C for 0.5 h
and then allowed to warm to room temperature. After
the usual workup, the resultant rearranged products
were reduced with LiAlH4 without purification. The
optical purities of the obtained alcohols were determined
by their conversion to the corresponding Mosher’s esters.
As shown in Table 4, (E)- or (Z)-substrates provided
syn or anti isomers, respectively. High diastereoselection
as well as complete transfer of chirality was observed in
both isomers; however, the diastereomeric excesses of syn
isomers were a little higher than those of anti isomers,
The determination of the absolute stereochemistry was
carried out as described in Scheme 7. Reduction of anti-
9c and hydrogenation under 10 atm afforded the corre-
sponding diol 15. This material was treated with Pb-
(OAc)4 to give the aldehyde, which was further reduced
with LiAlH4 without purification. Conversion of 16 to
the corresponding bromide was accomplished with CBr4/
PPh3, followed by an SN2 reaction by thiolate, affording
the desired compound 17.
On the other hand, reduction of 186 and Swern oxida-
tion of the resultant alcohol led to aldehyde 19 which
underwent successive Wittig reaction and hydrogenation
to furnish 17. By comparison of optical rotation values
of 17 and from the result described in Scheme 6, the
absolute configurations of anti-9a -c and anti-11a ,c were
determined as (2S,3R). A significant decrease of the
optical rotation value of 17 relative to that of anti-9c was
(24) Koreeda, M.; Luengo, J . I. J . Am. Chem. Soc. 1985, 107, 5572.

142 J . Org. Chem., Vol. 62, No. 1, 1997
Ta ble 4. [3,3]-Ir ela n d -Cla isen Rea r r a n gem en t
Konno et al.
observed because partial epimerization occurred in the
oxidative cleavage of 15.25
envelopelike transition state suggested by Nakai,13,26
Houk,27 and Bru¨ckner.28 Generally, it has been accepted
that the stereoselective sense of the ester enolate [2,3]-
Wittig shift is opposite to that of the reaction that
involves an alkynyl group, an alkenyl group, and so on
(except for a carbonyl moiety) as a migrating terminus.
It is Houk’s model at present that could explain not only
the general trends of the stereoselectivities for bisallyl
ether and/or allyl propargyl ether but also the exception
of the enolate [2,3]-Wittig shift (Figure 1). Thus, in the
On the other hand, syn-11c was transformed into the
enantiomeric 16 by the same method described above
(Scheme 8). Moreover, ozonolysis of syn-11a -c and the
following reduction provided the same compound 20
which is the diastereomer of 14. From these results, the
relative configuration of syn-11a -c was proven to be syn,
and the absolute stereochemistry of syn-11a and 11c
were determined to be (2S,3S).
Mech a n ism . The mechanism of the [2,3]-Wittig rear-
rangement has been represented thus far by the postu-
late that the reaction proceeds via the five-membered
(26) Mikami, K.; Kimura, Y.; Kishi, N.; Nakai, T. J . Org. Chem.
1983, 48, 281.
(27) Wu, Y.-D.; Houk, K. N.; Marshall, J . A. J . Org. Chem. 1990,
55, 1421.
(25) It has already been reported that, in the preparation of R-CF3
aldehyde, reaction under acidic condition gave optically active com-
pound, whereas complete epimerization was observed even under such
weakly basic condition as aqueous NaHCO3, see ref 13c.
(28) (a) Priepke, H.; Bru¨ckner, R. Chem. Ber. 1990, 123, 153. (b)
Bru¨ckner, R. Chem. Ber. 1989, 122, 703. (c) Priepke, H.; Bru¨ckner,
R. Angew. Chem., Int. Ed. Engl. 1988, 27, 278. (d) Scheuplein, S. W.;
Kusche, A.; Bru¨ckner, R.; Harms, K. Chem. Ber. 1990, 123, 917.

Stereoselective Synthesis of Trifluoromethylated Compounds
Sch em e 6a
J . Org. Chem., Vol. 62, No. 1, 1997 143
Sch em e 7a
Sch em e 8a
distance. Accordingly, it is expected that the migrating
terminus G might occupy the endo position. On the other
hand, a negative charge develops at C1 in the transition
state. Consequently, an endo π-acceptor substituent
should stabilize the transition state, while an endo
“early” transition state calculated by Houk et al., the Hb-
G(exo) distance is much shorter than the Ha-G(endo)

144 J . Org. Chem., Vol. 62, No. 1, 1997
Konno et al.
F igu r e 2.
Concerning the mechanism for the [3,3]-Ireland-
Claisen variant, on the other hand, the postulate sug-
gested for hydrocarbon chemistry is applicable to our
system. Thus, it might be unambiguous that this rear-
rangement proceeded via a six-membered transition state
in which a lithium atom coordinates to an oxygen atom
of a methoxy group to afford (Z)-ketene silyl acetal
preferentially (Figure 2).33 In the six-membered transi-
tion state A or B derived from E or Z isomer, a CF3 group,
considered to be sterically similar to an isopropyl group,30
might occupy the equatorial or axial position, respec-
tively. The bulkiness of a CF3 group might result in the
destabilization of transition state B due to 1,3-diaxial
interaction between the CF3 group and hydrogen atom,
causing a decrease of anti stereoselectivity.
F igu r e 1.
π-donor should destabilize the transition state. There-
fore, an alkynyl group, a cyano group and so on might
occupy the exo position, while a formyl group might
occupy the endo position. Then, in the ester-enolate [2,3]-
Wittig rearrangement, (E)-substrate (Ha ) H, Hb * H)
might give syn isomer, while (Z)-substrate (Ha * H, Hb
) H) might produce anti isomer.29 In the present study,
the hypothesis is applicable. Considering the bulkiness
of a CF3 group,30 it is highly possible that in the transition
state derived from (Z)-substrates, a CO2Me group might
occupy the endo position which is antiperiplanar to a CF3
group. This would be because the endo occupation is
considered to be doubly favorable from the viewpoint of
the steric as well as electrostatic interaction. Thus, a
CO2Me group might not occupy the exo position due to
the large gauche repulsion with a CF3 group and no
stabilization of the negative charge at C1. Therefore, the
(Z)-isomer gives anti product in a highly stereoselective
manner. In the transition state derived from (E)-
substrates, on the other hand, the bulkiness of a CF3
group might result in the destabilization of its endo
positioning due to severe gauche repulsion between a CF3
and a CO2Me group, leading to the decrease in syn
stereoselection. In addition, it is deduced that the Hb-
CHO(exo) gauche repulsion is larger than the 1,3-diaxial
interaction between a substituent R (Hc ) R) and Hb
from the experimental result obtained with the syn-Z
product.31,32
Su m m a r y
In conclusion, we have investigated ester-enolate [2,3]-
Wittig and [3,3]-Ireland-Claisen rearrangements of vari-
ous types of substrates, including chiral materials ob-
tained by extremely effective enzymatic kinetic resolution.
As described above, it was revealed that the [2,3]-Wittig
shift is effective for the preparation of anti isomers in
(31) Koreeda et al. have been reported that the following substrate
gave anti isomer in a highly stereoselective fashion. The unusual
selectivity has been explained by the envelope-like transition state C
suggested by Rautenstrauch (Koreeda, M.; Ricca, D. J . Org. Chem.
1986, 51, 4090.)
(32) We have already performed ab initio calculation (3-21G full
optimization) of the transition state derived from CF3-containing (E)-
or (Z)-substrate. It was supposed that HMPA employed as a cosolvent
might be a scavenger for lithium cation. Therefore, the transition state
without this cation was calculated which is different from Houk’s one.
As a result, (Z)-substrate affords anti product in a highly stereoselective
manner, while (E)-substrate also provides anti isomer stereoselectively.
Furthermore, surprisingly, the second stable TS derived from (E)-
isomer is the one which might produce anti isomer possessing Z
configuration at the newly created olefinic bond.
(33) (a) Burke, S. D.; Fobare, W. F.; Pacofsky, G. J . J . Org. Chem.
1983, 48, 5221. (b) Gould, T. J .; Balestra, M.; Wittman, M. D.; Gary,
J . A.; Rossano, L. T.; Kallmerten, J . J . Org. Chem. 1987, 52, 3889. (c)
Kallmerten, J .; Gould, T. J . Tetrahedron Lett. 1983, 24, 5177. (d)
Bartlett, P. A.; Tanzella, D.; Barstow, J . F. J . Org. Chem. 1982, 47,
3941.
(29) In the enolate [2,3]-Wittig rearrangement without transition
metal species, high syn selection using E-substrate (low anti selection
using Z-substrate) has been reported. For example, see the following
reference. Uchikawa, M.; Katsuki, T.; Yamaguchi, M. Tetrahedron
Lett. 1986, 27, 4581. There have been several examples that ester-
enolate [2,3]-Wittig shift of Z substrate showed high anti stereoselec-
tion. See ref 28.
(30) Bott, G.; Field, L. G.; Sternhell, S. J . Am. Chem. Soc. 1980,
102, 5618.

Stereoselective Synthesis of Trifluoromethylated Compounds
J . Org. Chem., Vol. 62, No. 1, 1997 145
Sch em e 9
(q, J ) 1.4 Hz), 73.32, 82.26 (q, J ) 6.6 Hz), 113.63 (q, J )
257.9 Hz), 127.66, 127.96, 128.45, 137.05, 169.25. 19F NMR
(CDCl3) δ 110.863 (s). IR (neat) ν 3067, 3035, 2940, 2869, 2282,
optically as well as diastereomerically pure forms, while
this transformation furnishes lower selectivity in the
formation of the corresponding syn isomers. On the other
hand, the [3,3]-Ireland-Claisen shift was found to play
a complementary role and furnishes the structurally
equivalent 11 as a single product. Thus, these processes
enable us to provide all stereoisomers of very useful
synthetic intermediates which possess a variety of chemi-
cally distinguishable functionalities (an allylic alcohol,
a hydroxyl, and a carboxyl moiety) (Scheme 9).
1756. [R]28 ) +40.9 (c 1.2, CHCl3) (86% ee). Anal. Calcd
D
for C14H13O3F3: C, 58.74; H, 4.58. Found: C, 58.36; H, 4.80.
(3S)-1-(Tr iflu or om eth yl)-1-octyn -3-ol ((S)-4c). Yield: 45%
(0.353 g, 1.82 mmol). Lipase PL (0.548 g, 49320 U; Alcaligenes
sp. Meito Sangyo Co., Lid., J apan) was employed as an enzyme.
Physical properties of this compound were the same as the
ones described in the literature18f except for the optical
rotation. [R]14 ) -4.1 (c 0.8, CHCl3) (>99% ee).
D
(3R)-3-Acetoxy-1-(tr iflu or om eth yl)-1-octyn e. Yield: 51%
(0.484 g, 2.05 mmol). 1H NMR (CDCl3) δ 0.90 (3 H, t, J )
6.84 Hz), 1.30-1.50 (6 H, m), 1.70-1.90 (2 H, m), 2.11 (3 H,
s), 5.86 (1 H, tq, J ) 2.93, 5.86 Hz). 13C NMR (CDCl3) δ 13.80,
20.61, 22.32, 24.34, 31.05, 33.62, 62.48, 72.09 (q, J ) 53.0 Hz),
84.66 (q, J ) 6.4 Hz), 113.83 (q, J ) 257.6 Hz), 169.53. 19F
NMR (CDCl3) δ 11.14 (d, J ) 3.05 Hz). IR (neat) ν 2950, 2934,
Exp er im en ta l Section
Gen er a l.18f Gas liquid chromatography (GLC) was per-
formed using Silicone GE XE-60 or ULBON HR-20M on
Chromosorb W, 30 m × 3 mm. NMR patterns of minor isomers
are the same as those of major one, with an exception of signals
indicated.
2864, 2274, 1753. [R]15 ) +50.8 (c 0.7, CHCl3) (81% ee).
D
Gen er a l P r oced u r e for En zym a tic Tr a n sester ifica -
tion . To a 0.17 M solution of a racemic propargylic alcohol
rac-4 (4.03 mmol) in n-hexane (24 mL) were added vinyl
acetate (8.10 mL, 97.4 mmol) and an enzyme, and the whole
was stirred at 30 °C for 24 h. After removal of the residue by
filtration and concentration of this solution, separation by
silica gel column chromatography afforded an optically active
alcohol and an ester. The enantiomeric excess was determined
by capillary GC after derivatization into the corresponding
MTPA esters.
Deter m in a tion of Ster eoch em istr y of (S)-5a . A solution
of (S)-5a (0.95 g, 3.32 mmol) and K2CO3 (2.29 g, 16.6 mmol)
in methanol (15 mL) was stirred at room temperature for 1 h
and then evaporated in vacuo. After complete removal of
methanol, the crude oil was diluted with ether and the whole
was washed with water and brine, dried over anhydrous
MgSO4, and then evaporated. The resulting materials were
purified by silica gel column chromatography to furnish the
propargyl alcohol, which was converted into the corresponding
allylic alcohol by the same method as described in the
literature.18 To a solution of the obtained allylic alcohol and
acetyl chloride (0.22 mL, 3.16 mmol) in CH2Cl2 (10 mL) was
added pyridine (0.25 mL, 3.16 mL) at 0 °C, and then the whole
was allowed to warm to room temperature and stirred for 2
h. The reaction was quenched with 3 N aqueous HCl, and
the mixture was extracted with CH2Cl2. The organic layer was
washed with water, dried over anhydrous MgSO4, and then
evaporated to give crude materials which were treated with
ozone at -78 °C in methanol for 30 min. Dimethyl sulfide
(1.0 mL) was added to the reaction mixture, and the whole
was stirred at that temperature for 30 min and then allowed
to warm to room temperature and stirred for 30 min. After
(3R)-4-(Ben zyloxy)-1-(tr iflu or om eth yl)-1-bu tyn -3-ol ((R)-
4a ). Yield: 45% (0.445 g, 1.82 mmol). Novozym 435 (0.984
g, 6888 PLU; Novo Nordisk, Denmark) was employed as an
enzyme. Physical properties of this compound were the same
as the ones described in the literature18f except for the optical
rotation. [R]27 ) -2.4 (c 1.0, CHCl3) (>99% ee).
D
(3S)-3-Acetoxy-4-(ben zyloxy)-1-(tr iflu or om eth yl)-1-bu -
t yn e ((S)-5a ). Yield: 47% (0.545 g, 1.90 mmol). 1H NMR
(CDCl3) δ 2.14 (3 H, s), 3.71 (1 H, dd, J ) 4.88, 10.74 Hz),
3.74 (1 H, dd, J ) 6.11, 10.74 Hz), 4.58 (1 H, d, J ) 12.21 Hz),
4.63 (1 H, d, J ) 12.20 Hz), 5.60-5.66 (1 H, m), 7.20-7.40 (5
H, m). 13C NMR (CDCl3) δ 20.45, 61.58 (q, J ) 2.7 Hz), 69.58

146 J . Org. Chem., Vol. 62, No. 1, 1997
Konno et al.
removal of solvent, the obtained crude materials were im-
mediately reduced with NaBH4 (0.076 g, 2.0 mmol) in ethanol
(5 mL) (rt, 30 min). Usual workup gave the crude materials
which were purified by silica gel column chromatography to
afford the alcohol which was acetylated by the usual method
(AcCl, 0.102 mL, 1.43 mmol; pyridine, 0.116 mL, 1.43 mmol)
to give the desired compound (0.25 g, 0.95 mmol).
(4R)-Meth yl (Z)-6-(Tr iflu or om eth yl)-3-oxa -4-[2-(ben z-
yloxy)eth yl]-5-h exen oa te ((R)-(Z)-8b). Yield: 84%. Rf )
0.25 (hexane:CH2Cl2 ) 1:1). 1H NMR (CDCl3) δ 1.85 (1 H, ddt,
J ) 5.86, 7.08, 13.43 Hz), 2.00 (1 H, ddt, J ) 5.86, 8.06, 13.92
Hz), 3.59 (1 H, dt, J ) 6.11, 9.77 Hz), 3.66 (1 H, ddd, J ) 5.86,
7.57, 9.52 Hz), 3.73 (3 H, s), 3.98 (1 H, d, J ) 16.11 Hz), 4.06
(1 H, d, J ) 16.36 Hz), 4.48 (1 H, d, J ) 11.96 Hz), 4.52 (1 H,
d, J ) 11.72 Hz), 4.54-4.60 (1 H, m), 5.79 (1 H, ddq, J ) 0.73,
8.79, 11.72 Hz), 5.95 (1 H, dd, J ) 9.77, 11.72 Hz). 13C NMR
(CDCl3) δ 35.14, 51.68, 65.69, 66.10, 72.77, 73.04, 120.69 (q, J
) 34.4 Hz), 122.57 (q, J ) 272.9 Hz), 127.41, 127.51, 128.23,
138.30, 141.97 (q, J ) 4.7 Hz), 170.31. 19F NMR (CDCl3) δ
(2R)-1,2-Dia cet oxy-3-(b en zyloxy)p r op a n e
((R)-6).
Yield: 29%. Physical properties of this compound were the
same as the ones described in the literature19 except for the
optical rotation. [R]25 ) -14.3 (c 0.9, CHCl3).
D
Deter m in a tion of Ster eoch em istr y of (S)-4c. Chiral
propargyl alcohol (S)-4c (0.68 g, 3.51 mmol) was converted into
(S)-2-acetoxyheptan-1-ol (0.23 g, 1.45 mmol) by the same
method as described in the determination of stereochemistry
of (S)-5a (1. Partial hydrogenation by Lindlar cat./H2. 2.
104.28 (d, J ) 7.63 Hz). IR (neat) ν 2957, 2867, 1750. [R]15
D
) -17.7 (c 0.7, CHCl3). HRMS calcd for C16H19O4F3 332.1235.
Found 332.1240.
Meth yl (E)-6-(Tr iflu or om eth yl)-3-oxa -4-[2-(ben zyloxy)-
eth yl]-5-h exen oa te (r a c-(E)-8b). Yield: 85%. Rf ) 0.21
(hexane:EtOAc ) 3:1). 1H NMR (CDCl3) δ 1.86 (1 H, ddt, J )
5.12, 7.82, 13.97 Hz), 1.96 (1 H, dddd, J ) 5.13, 5.96, 8.06,
12.94 Hz), 3.55 (1 H, dt, J ) 5.61, 9.52 Hz), 3.68 (1 H, ddd, J
) 4.63, 7.56, 9.27 Hz), 3.74 (3 H, s), 4.60 (1 H, d, J ) 16.11
Hz), 4.10 (1 H, d, J ) 16.11 Hz), 4.13-4.19 (1 H, m), 4.48 (1
H, d, J ) 11.72 Hz), 5.85 (1 H, ddq, J ) 1.22, 6.34, 15.86 Hz),
Acetylation. 3. Ozonolysis. 4. Reduction by NaBH4).
A
solution of the obtained alcohol and K2CO3 (0.629 g, 4.55 mmol)
in methanol (10 mL) was stirred at room temperature for 30
min, and usual workup gave the diol (0.12 g, 0.91 mmol). (S)-
1,2-Heptanediol. Yield: 26%. Physical properties of this
compound were the same as the ones described in the
literature20 except for the optical rotation. [R]15 ) -11.9 (c
D
6.29 (1 H, ddq, J ) 1.95, 6.35, 15.87 Hz), 7.2-7.4 (5 H, m). 13
C
0.8, MeOH).
NMR (CDCl3) δ 35.00, 51.76, 65.57, 72.96, 76.34, 119.80 (q, J
) 34.0 Hz), 122.67 (q, J ) 269.7 Hz), 127.60, 127.68, 128.32,
138.14, 139.29 (q, J ) 6.0 Hz). 19F NMR (CDCl3) δ 97.55 (d,
J ) 6.11 Hz). IR (neat) ν 3089, 3066, 3032, 2955, 2926, 2865,
1751, 1684. HRMS calcd for C12H19O3F3 332.1235. Found
332.1237.
(4S)-Meth yl (Z)-6-(Tr iflu or om eth yl)-3-oxa -4-p en tyl-5-
h exen oa te ((S)-(Z)-8c). Yield: 76%. Rf ) 0.47 (hexane:CH2-
Cl2 ) 1:1). 1H NMR (CDCl3) δ 0.88 (3 H, t, J ) 6.96 Hz), 1.3-
1.8 (8 H, m), 3.75 (3 H, s), 4.01 (1 H, d, J ) 16.36 Hz), 4.08 (1
H, d, J ) 16.36 Hz), 5.79 (1 H, dq, J ) 8.47, 11.97 Hz), 5.89 (1
H, dd, J ) 9.76, 11.96 Hz). 13C NMR (CDCl3) δ 13.83, 22.37,
24.38, 31.49, 34.87, 51.64, 65.94, 75.68, 120.73 (q, J ) 34.2
Hz), 122.62 (q, J ) 272.1 Hz), 142.48 (q, J ) 5.4 Hz), 170.44.
19F NMR (CDCl3) δ 104.40 (d, J ) 9.15 Hz). IR (neat) ν 2958,
2935, 2863, 1760, 1671. [R]14D ) -33.2 (c 0.7, CHCl3). HRMS
calcd for C12H19O3F3 268.1286. Found 268.1293.
Met h yl (Z)-6-(Tr iflu or om et h yl)-3-oxa -4-cycloh exyl-5-
h exen oa te (r a c-(Z)-8d ). Yield: 66%. Rf ) 0.60 (hexane:CH2-
Cl2 ) 1:1). 1H NMR (CDCl3) δ 0.9-2.1 (11 H, m), 3.73 (3 H,
s), 3.98 (1 H, d, J ) 16.36 Hz), 4.07 (1 H, d, J ) 16.60 Hz),
4.05-4.10 (1 H, m), 5.7-5.9 (2 H, m). 13C NMR (CDCl3) δ
25.73, 25.86, 26.24, 28.24, 28.64, 42.03, 51.49, 65.76, 79.60,
121.69 (q, J ) 33.9 Hz), 122.58 (q, J ) 272.0 Hz), 140.99 (q, J
) 4.8 Hz), 170.47. 19F NMR (CDCl3) δ 104.83 (d, J ) 7.63
Hz). IR (neat) ν 3004, 2932, 2856, 1760, 1670. HRMS calcd
for C13H19O3F3 280.1286. Found 280.1258.
Gen er a l P r oced u r e of th e P r ep a r a tion for Su bstr a tes
of [2,3]-Wittig Rea r r a n gem en t. To a suspension of NaH
(ca. 0.16 g, 4 mmol) in THF (10 mL) was added dropwise a
solution of allylic alcohol (2 mmol) in THF (5 mL) at 0 °C which
was prepared from the corresponding propargyl alcohol by the
same method as described in the literature,18f and the mixture
was stirred for 10 min. To this was added a solution of
bromoacetic acid (0.278 g, 2 mmol) in THF (5 mL) at 0 °C.
The reaction mixture was stirred overnight at room temper-
ature and poured into ice-cooled water. The organic layer was
extracted with 1 N aqueous NaOH three times, the combined
aqueous layers were acidified with 3 N HCl, and the whole
was extracted with ether three times. The organic solution
was dried over anhydrous MgSO4, and then evaporated. To a
solution of crude carboxylic acid in CH2Cl2 (10 mL) were added
(COCl)2 (0.349 mL, 4.0 mmol) and a catalytic amount of DMF
(two drops) at 0 °C, and the mixture was stirred overnight at
ambient temperature. The solvent and an excess amount of
(COCl2) were removed under reduced pressure, to this were
added CH2Cl2 (10 mL), MeOH (1 mL), and pyridine (0.34 mL,
4.19 mmol) at 0 °C, and the reaction mixture was stirred
overnight at room temperature, poured into 3 N aqueous HCl,
and extracted with CH2Cl2 three times. The organic extracts
were dried over anhydrous MgSO4 and evaporated. The
residue was purified by silica gel column chromatography to
afford the ester.
(4R)-Met h yl (Z)-6-(Tr iflu or om et h yl)-3-oxa -4-[(b en z-
yloxy)m eth yl]-5-h exen oa te ((R)-(Z)-8a ). Yield: 85%. Rf )
0.34 (hexane:CH2Cl2 ) 1:3). 1H NMR (CDCl3) δ 3.62 (1 H, dd,
J ) 4.15, 10.74 Hz), 3.65 (1 H, dd, J ) 5.38, 10.50 Hz), 3.74 (3
H, s), 4.12 (1 H, d, J ) 16.60 Hz), 4.18 (1 H, d, J ) 16.61 Hz),
4.57 (1 H, d, J ) 12.21 Hz), 4.60 (1 H, d, J ) 12.20 Hz), 4.6-
4.7 (1 H, m), 5.84 (1 H, ddq, J ) 0.98, 7.57, 11.96 Hz), 6.05 (1
H, dd, J ) 9.52, 11.96 Hz), 7.2-7.4 (5 H, m). 13C NMR (CDCl3)
δ 51.64, 66.35, 71.92, 73.25, 75.03, 121.57 (q, J ) 34.2 Hz),
122.44 (q, J ) 272.2 Hz), 127.46, 127.54, 128.22, 137.69, 139.07
(q, J ) 5.1 Hz), 170.26. 19F NMR (CDCl3) δ 103.98 (d, J )
9.16 Hz). IR (neat) ν 3065, 3033, 3006, 2925, 2916, 2863, 1758,
Meth yl (Z)-6-(Tr iflu or om eth yl)-3-oxa-4-(1-ph en yleth yl)-
5-h exen oa te (r a c-(Z)-8e). Yield: 86%. Rf ) 0.32 (hexane:
CH2Cl2 ) 1:1). Diastereoselectivity ) 89:11. IR (neat) ν 3063,
3031, 2970, 2915, 2851, 1758, 1671. HRMS calcd for C15H17O3F3
302.1130. Found 302.1158. (Major isomer) 1H NMR (CDCl3)
δ 1.42 (3 H, d, J ) 7.08 Hz), 3.00 (1 H, quint, J ) 6.96 Hz),
3.73 (3 H, s), 3.98 (1 H, d, J ) 16.60 Hz), 4.09 (1 H, d, J )
16.36 Hz), 4.4-4.5 (1 H, m), 5.66 (1 H, ddq, J ) 0.74, 8.54,
11.96 Hz), 5.78 (1 H, dd, J ) 10.26, 11.97 Hz), 7.1-7.4 (5 H,
m). 13C NMR (CDCl3) δ 16.56, 44.73, 51.54, 65.95, 79.28,
121.16 (q, J ) 34.0 Hz), 122.46 (q, J ) 272.0 Hz), 126.70,
128.03, 128.08, 141.84, 140.10 (q, J ) 5.0 Hz), 170.37. 19F
1676. [R]16 ) -36.7 (c 0.8, CHCl3). Anal. Calcd for
D
1
C15H17O4F3: C, 56.60; H, 5.38. Found: C, 56.44; H, 5.61.
Met h yl (E)-6-(Tr iflu or om et h yl)-3-oxa -4-[(ben zyloxy)-
m eth yl]-5-h exen oa te (r a c-(E)-8a ). Yield: 74%. 1H NMR
(CDCl3) δ 3.58 (1 H, dd, J ) 4.52, 10.14 Hz), 3.63 (1 H, dd, J
) 6.23, 10.13 Hz), 3.73 (3 H, s), 4.18 (1 H, d, J ) 16.36 Hz),
4.25 (1 H, d, J ) 16.36 Hz), 4.2-4.3 (1 H, m), 4.55 (1 H, d, J
) 12.21 Hz), 4.58 (1 H, d, J ) 11.96 Hz), 6.00 (1 H, ddq, J )
1.57, 6.47, 15.75 Hz), 6.35 (1 H, ddq, J ) 2.06, 5.37, 15.87 Hz),
7.2-7.4 (5 H, m). 13C NMR (CDCl3) δ 51.68, 66.99, 71.79,
73.34, 77.82, 120.60 (q, J ) 34.1 Hz), 122.72 (q, J ) 269.4 Hz),
127.55, 127.69, 128.32, 137.56, 136.63 (q, J ) 6.2 Hz) 170.35.
19F NMR (CDCl3) δ 97.42 (d, J ) 6.10 Hz). IR (neat) ν 3066,
3032, 2956, 2910, 2865, 1757, 1685.
NMR (CDCl3) δ 104.36 (d, J ) 7.63 Hz). (Minor isomer) H
NMR (CDCl3) δ 1.31 (3 H, d, J ) 7.32 Hz), 2.92 (1 H, quint, J
) 7.24 Hz), 3.67 (3 H, s), 3.88 (1 H, d, J ) 16.36 Hz), 3.99 (1
H, d, J ) 16.60 Hz), 4.50-4.55 (1 H, m). 13C NMR (CDCl3) δ
17.67, 44.39, 66.07, 79.37, 121.53 (q, J ) 34.2 Hz), 126.53,
127.88, 128.26, 142.16, 140.98 (q, J ) 4.9 Hz) 170.24. 19F NMR
(CDCl3) δ 104.64 (d, J ) 7.63 Hz).
Gen er a l Meth od for [2,3]-Wittig Rea r r a n gem en t. To
a solution of diisopropylamine (0.622 mmol, 0.093 mL) in THF
(5 mL) was added a 1.6 M solution of n-BuLi in hexane (0.622
mmol, 0.41 mL) at -78 °C, HMPA (0.34 mL, 1.95 mmol) was
added, and the resulting clear solution was stirred for 30 min
at that temperature. To this was added a solution of ester

Stereoselective Synthesis of Trifluoromethylated Compounds
J . Org. Chem., Vol. 62, No. 1, 1997 147
(0.331 mmol) in THF (2 mL), and the mixture was stirred at
that temperature for 10 min. At this point, the ester disap-
peared completely (monitored by TLC). Then the reaction
mixture was poured into ice-cooled 3 N aqueous HCl and
extracted with ethyl acetate. The organic layer was dried over
anhydrous MgSO4 and concentrated in vacuo. After a puri-
fication of silica gel column chromatography, the hydroxy ester
was obtained.
2.94 (1 H, d, J ) 5.37 Hz), 3.12 (1 H, dquint, J ) 2.20, 9.28
Hz), 3.80 (3 H, s), 4.63 (1 H, dd, J ) 1.95, 5.61 Hz), 5.41 (1 H,
ddd, J ) 1.22, 9.76, 15.62 Hz), 5.63 (1 H, dd, J ) 6.84, 15.63
Hz). 13C NMR (CDCl3) δ 25.09, 25.72, 25.94, 32.45, 32.48,
40.66, 50.43 (q, J ) 26.9 Hz), 53.00, 69.56 (q, J ) 2.4 Hz),
114.74 (q, J ) 2.4 Hz), 125.78 (q, J ) 280.7 Hz). 19F NMR
(CDCl3) δ 93.30 (d, J ) 9.16 Hz). IR (neat) ν 3501, 2928, 2854,
1746. HRMS calcd for C13H19O3F3 280.1286. Found 280.1287.
(2S,3S)-Meth yl 6-(Ben zyloxy)-3-(tr iflu or om eth yl)-2-h y-
d r oxy-4(E)-h exen oa te (a n ti-9a ). Yield: 73%. 1H NMR
(CDCl3) δ 2.99 (1 H, d, J ) 5.37 Hz), 3.27 (1 H, dquint, J )
1.96, 9.04 Hz), 3.82 (3 H, s), 3.97-4.07 (2 H, m), 4.48 (2 H, s),
4.66 (1 H, dd, J ) 1.95, 5.13 Hz), 5.77 (1 H, dd, J ) 9.28, 15.63
Hz), 5.85 (1 H, dd, J ) 5.13, 15.87 Hz), 7.20-7.40 (5 H, m).
13C NMR (CDCl3) δ 50.02 (q, J ) 27.1 Hz), 53.23, 69.15 (q, J
) 2.5 Hz), 69.47, 71.91, 120.21 (q, J ) 2.5 Hz), 125.54 (q, J )
280.6 Hz), 127.71, 127.73, 128.41, 136.00, 137.82, 172.58. 19F
NMR (CDCl3) δ 93.43 (d, J ) 7.63 Hz). IR (neat) ν 3500, 3150,
(2S*,3S*)-Met h yl 3-(Tr iflu or om et h yl)-2-h yd r oxyl-6-
p h en yl-4(E)-h ep ten oa te (a n ti-9e). Yield: 85%. Rf ) 0.17
(hexane:CH2Cl2 ) 1:1). Diastereoselectivity ) 88:12. IR (neat)
ν 3504, 3084, 3029, 2965, 2933, 2876, 1744. HRMS calcd for
C
15H17O3F3 302.1130. Found 302.1111. (Major isomer) 1H
NMR (CDCl3) δ 1.36 (3 H, d, J ) 7.08 Hz), 2.99 (1 H, d, J )
5.12 Hz), 3.18 (1 H, dquint, J ) 2.04, 9.28 Hz), 3.48 (1 H, quint,
J ) 6.59 Hz), 3.60 (3 H, s), 4.6-4.65 (1 H, m), 5.54 (1 H, ddd,
J ) 1.22, 9.77, 15.63 Hz), 5.84 (1 H, dd, J ) 7.20, 15.50 Hz),
7.1-7.3 (5 H, m). 13C NMR (CDCl3) δ 20.41, 42.32, 50.31 (q,
J ) 27.2 Hz), 52.89, 69.31 (q, J ) 2.5 Hz), 116.03 (q, J ) 2.4
Hz), 125.70 (q, J ) 280.5 Hz), 126.33, 127.03, 128.46, 144.94,
144.46, 172.54. 19F NMR (CDCl3) δ 93.43 (d, J ) 9.41 Hz).
(Minor isomer) 1H NMR (CDCl3) δ 1.34 (3 H, d, J ) 7.08 Hz),
3.04 (1 H, d, J ) 5.13 Hz), 3.71 (3 H, s), 4.64-4.7 (1 H, m),
5.58 (1 H, ddd, J ) 1.59, 9.64, 15.87 Hz), 5.89 (1 H, dd, J )
6.10, 15.87 Hz). 13C NMR (CDCl3) δ 20.32, 41.97, 50.38 (q, J
) 27.0 Hz), 52.97, 69.36 (q, J ) 1.9 Hz), 115.82 (q, J ) 2.5
Hz), 126.37, 127.10, 144.54. 19F NMR (CDCl3) δ 93.45 (d, J )
10.82 Hz).
3100, 3050, 3000, 2956, 2860, 1746. [R]17 ) +10.1 (c 0.3,
D
CHCl3).
(2S*,3R*)-Meth yl 6-(Ben zyloxy)-3-(tr iflu or om eth yl)-2-
h yd r oxy-4(E)-h exen oa te (syn -9a ). Yield: 61% (A small
amount of unidentified compounds was included, which could
not be separated from the desired ester). IR (neat) ν 3458,
3090, 3070, 3032, 2956, 2861, 1747. 1H NMR (CDCl3) δ 3.00
(1 H, s), 3.33 (1 H, dquint, J ) 3.42, 8.91 Hz), 3.82 (1 H, m),
3.83 (3 H, s), 4.06 (1 H, m), 4.07 (1 H, m), 4.52 (2 H, m), 5.84
(1 H, ddt, J ) 1.34, 9.16, 15.38 Hz), 5.99 (1 H, dt, J ) 5.50,
15.63 Hz), 7.27-7.38 (5 H, m). 13C NMR (CDCl3) δ 50.62 (q,
J ) 25.7 Hz), 53.00, 69.58, 70.04 (q, J ) 2.0 Hz), 72.31, 122.34
(q, J ) 2.5 Hz), 124.99 (q, J ) 269.2 Hz), 126.95, 127.73,
127.79, 135.07, 137.81, 172.50. 19F NMR (CDCl3) δ 93.55 (d,
J ) 9.16 Hz) (for anti-E isomer) 95.59 (d, J ) 7.63 Hz) (for
syn-E isomer) 95.64 (d, J ) 7.62 Hz) (for syn-Z isomer).
(2S,3S)-Meth yl 7-(Ben zyloxy)-3-(tr iflu or om eth yl)-2-h y-
d r oxyl-4(E)-h ep ten oa te (a n ti-9b). Yield: 78%. Rf ) 0.08
(hexane:CH2Cl2 ) 1:1). 1H NMR (CDCl3) δ 2.3-2.5 (2 H, m),
3.18 (1 H, dquint, J ) 1.95, 9.28 Hz), 3.49 (1 H, dt, J ) 6.60,
12.94 Hz), 3.50 (1 H, dt, J ) 6.35, 12.70 Hz), 3.76, (3 H, s),
4.4-4.5 (2 H, m), 4.5-4.6 (1 H, m), 5.79 (1 H, dt, J ) 6.96,
15.63 Hz), 5.56 (1 H, dd, J ) 9.64, 15.38 Hz), 7.2-7.4 (5 H,
m). 13C NMR (CDCl3) δ 32.97, 50.32 (q, J ) 27.0 Hz), 53.03,
69.3 (q, J ) 1.8 Hz), 72.87, 119.18 (q, J ) 2.2 Hz), 125.68 (q,
J ) 280.2 Hz), 127.59, 128.34, 136.86, 138.15, 172.59. 19F
NMR (CDCl3) δ 93.33 (d, J ) 9.15 Hz). IR (neat) ν 3032, 2956,
2929, 2861, 1747. [R]17D ) +11.9 (c 0.7, CHCl3). HRMS calcd
for C16H19O4F3 332.1235. Found 332.1239.
(2S*,3R*)-Meth yl 7-(Ben zyloxy)-3-(tr iflu or om eth yl)-2-
h yd r oxyl-4(E)-h ep ten oa te (syn -9b). Yield: 46% (A small
amount of unidentified compounds was included, which could
not be separated from the desired ester). 1H NMR (CDCl3) δ
2,42 (2 H, dq, J ) 1.46, 6.59 Hz), 3.25 (1 H, dquint, J ) 3.66,
8.79 Hz), 3.40-3.70 (1 H, m), 3.54 (2 H, J ) 7.05 Hz), 3.81 (3
H, s), 4.32 (1 H, d, J ) 3.42 Hz), 4.51 (2 H, s), 5.57-5.64 (1 H,
m), 5.89 (1 H, dt, J ) 7.08, 15.62 Hz). 13C NMR (CDCl3) δ
32.91, 51.14 (q, J ) 26.0 Hz), 52.85, 69.12, 70.15 (q, J ) 2.1
Hz), 72.87, 121.28 (q, J ) 2.6 Hz), 125.48 (q, J ) 281.2 Hz),
127.60, 127.70, 128.35, 134.23, 136.01, 172.57. 19F NMR
(CDCl3) δ 95.40 (d, J ) 10.68 Hz), 95.42 (d, J ) 9.16 Hz) (for
E- or Z-isomer). IR (neat) ν 3482, 3090, 3070, 3032, 2956,
2980, 2961, 1748.
Gen er a l P r oced u r e of th e P r ep a r a tion for 3-(tr iflu o-
r om eth yl)a llyl Ester Der iva tives. To a solution of allylic
alcohol (1 mmol) in dry CH2Cl2 (5 mL) was added methoxy-
acetyl chloride (0.14 mL, 1.5 mmol) and pyridine (0.12 mL,
1.5 mmol) at 0 °C. The resulting solution was allowed to warm
to room temperature and then stirred at that temperature for
2 h. 1 N HCl was added to the reaction mixture, which was
extracted with CH2Cl2, washed with water, dried over anhy-
drous MgSO4, and evaporated in vacuo. The crude materials
were purified by silica gel column chromatography, affording
the ester.
(1′R)-3′-(Tr iflu or om eth yl)-1′-[(ben zyloxy)m eth yl]-(Z)-
2′-p r op en yl 2-Meth oxya ceta te ((R)-(Z)-10a ). Yield: 86%.
1H NMR (CDCl3) δ 3.44 (3 H, s), 3.64-3.66 (2 H, m), 4.04 (1
H, d, J ) 16.60 Hz), 4.08 (1 H, d, J ) 16.60 Hz), 4.52 (1 H, d,
J ) 11.96 Hz), 4.59 (1 H, d, J ) 12.2 Hz), 5.77 (1 H, dq, J )
8.55, 10.50 Hz), 6.0-6.1 (2 H, m), 7.3-7.4 (5 H, m). 13C NMR
(CDCl3) δ 59.16, 69.11, 69.42, 70.55, 73.05, 120.75 (q, J ) 34.8
Hz), 122.24 (q, J ) 271.8 Hz), 127.50, 127.71, 128.28, 136.43
(q, J ) 5.1 Hz), 132.32, 169.16. 19F NMR (CDCl3) δ 102.72 (d,
J ) 9.15 Hz). IR (neat) ν 3090, 3064, 3033, 2996, 2932, 2869,
1760, 1688. [R]27 ) -16.4 (c 1.3, CHCl3). Anal. Calcd for
D
C
15H17O4F3: C, 56.60; H, 5.38. Found: C, 56.63; H, 5.55.
3′-(Tr iflu or om eth yl)-1′-[2′′-(Ben zyloxy)eth yl]-(Z)-2′-pr o-
p en yl 2-Meth oxya ceta te (r a c-(Z)-10b). Yield: 88%. 1H
NMR (CDCl3) δ 1.8-2.1 (2 H, m), 3.40 (3 H, s), 3.53 (2 H, t, J
) 6.34 Hz), 3.94 (1 H, d, J ) 16.60 Hz), 3.98 (1 H, d, J ) 16.61
Hz), 4.44 (1 H, d, J ) 11.96 Hz), 4.51 (1 H, d, J ) 11.97 Hz),
5.68 (1 H, dq, J ) 8.54, 10.74 Hz), 5.93-5.99 (2 H, m), 7.2-
7.4 (5 H, m). 13C NMR (CDCl3) δ 34.26, 59.16, 65.32, 68.16
(q, J ) 1.5 Hz) 69.46, 72.82, 119.29 (q, J ) 34.9 Hz), 122.37
(q, J ) 271.7 Hz), 127.51, 127.56, 128.25, 137.94, 139.37 (q, J
) 5.0 Hz), 169.13. 19F NMR (CDCl3) δ 102.86 (d, J ) 7.63
Hz). IR (neat) ν 3089, 3064, 3032, 2993, 2931, 2867, 1760,
1688. Anal. Calcd for C16H19O4F3: C, 57.83; H, 5.76. Found:
C, 57.98; H, 5.98.
(2S,3S)-Met h yl 3-(Tr iflu or om et h yl)-2-h yd r oxyl-4(E)-
d ecen oa te (a n ti-9c). Yield: 64%. Rf ) 0.25 (hexane:CH2-
Cl2 ) 1:1). 1H NMR (CDCl3) δ 0.88 (3 H, t, J ) 7.08 Hz), 1.2-
1.4 (6 H, m), 2.0-2.1 (2 H, m), 2.96 (1 H, d, J ) 5.38 Hz), 3.16
(1 H, dquint, J ) 1.95, 9.28 Hz), 3.81 (3 H, s), 4.6-4.65 (1 H,
m), 5.4-5.5 (1 H, m), 5.70 (1 H, dt, J ) 6.84, 15.38 Hz). 13C
NMR (CDCl3) δ 13.95, 22.37, 28.46, 31.05, 32.48, 50.36 (q, J
) 26.9 Hz), 53.04, 69.38 (q, J ) 2.5 Hz), 117.05 (q, J ) 2.4
Hz), 125.77 (q, J ) 280.5 Hz), 140.63, 172.75. 19F NMR
(CDCl3) δ 93.21 (d, J ) 9.16 Hz). IR (neat) ν 3495, 2958, 2930,
2874, 2859, 1743. [R]14D ) +17.9 (c 0.6, CHCl3). HRMS calcd
for C12H19O3F3 268.1286. Found 268.1297.
(1′R)-3′-(Tr iflu or om eth yl)-1′-[(ben zyloxy)m eth yl]-(E)-
2′-p r op en yl 2-Meth oxya ceta te ((R)-(E)-10a ). Yield: 91%.
1H NMR (CDCl3) δ 3.46 (3 H, s), 3.60-3.64 (2 H, m), 4.10 (2
H, s), 4.53 (1 H, d, J ) 11.96 Hz), 4.58 (1 H, J ) 12.21 Hz),
5.66-5.72 (1 H, m), 5.89 (1 H, ddq, J ) 1.71, 6.35, 15.87 Hz),
6.40 (1 H, ddq, J ) 1.95, 5.13, 15.87 Hz), 7.2-7.4 (5 H, m). 13
C
NMR (CDCl3) δ 59.02, 69.26, 29.81, 70.52, 73.00, 120.39 (q, J
) 34.3 Hz) 122.41 (q, J ) 269.7 Hz) 127.45, 127.69, 128.25,
134.77 (q, J ) 6.5 Hz) 137.20, 169.00. 19F NMR (CDCl3) δ
97.15 (d, J ) 6.11 Hz). [R]28D ) +11.7 (c 0.9, CHCl3) (98% ee).
(2S*,3S*)-Meth yl 5-Cycloh exyl-3-(tr iflu or om eth yl)-2-
h yd r oxyl-4(E)-p en ten oa te (a n ti-9d ). Yield: 75%. Rf ) 0.22
(hexane:CH2Cl2 ) 1:1). 1H NMR (CDCl3) δ 0.9-2.0 (11 H, m),

148 J . Org. Chem., Vol. 62, No. 1, 1997
Konno et al.
IR (neat) ν 3060, 3050, 3033, 2934, 2868, 1762, 1686. Anal.
Calcd for C15H17O4F3: C, 56.60; H, 5.38. Found: C, 56.48; H,
5.58.
anhydrous MgSO4, and then evaporated in vacuo. To a
stirring of lithium aluminum hydride (0.059 g, 1.55 mmol) in
THF (3 mL) was added a THF solution of the resultant crude
materials at 0 °C, and the whole was stirred for 2 h at room
temperature. The reaction mixture was quenched with 4 N
aqueous KOH, and the usual workup gave the crude materials,
which were purified by silica gel column chromatography to
afford the alcohol.
3′-(Tr iflu or om eth yl)-1′-[2′′-(ben zyloxy)eth yl]-(E)-2′-p r o-
p en yl 2-Meth oxya ceta te (r a c-(E)-10b). Yield: 87%. 1H
NMR (CDCl3) δ 1.97 (1 H, ddq, J ) 5.86, 11.96, 14.40 Hz),
2.01 (1 H, ddq, J ) 5.62, 7.57, 14.41 Hz), 3.42 (3 H, s), 3.51 (2
H, t, J ) 5.85 Hz), 3.99 (1 H, d, J ) 16.36 Hz), 4.02 (1 H, d, J
) 16.35 Hz), 4.46 (1 H, d, J ) 11.72 Hz), 4.49 (1 H, d, J )
11.72 Hz), 5.68 (1 H, qq, J ) 1.95, 5.62 Hz), 5.81 (1 H, ddq, J
) 1.46, 6.34, 15.87 Hz), 6.35 (1 H, ddq, J ) 1.95, 5.86, 15.87
Hz), 7.2-7.4 (5 H, m). 13C NMR (CDCl3) δ 33.84, 59.21, 65.21,
69.48, 69.74, 73.01, 119.50 (q, J ) 34.3 Hz), 122.56 (q, J )
269.6 Hz), 127.64, 127.68, 128.32, 137.44 (q, J ) 6.4 Hz),
169.08. 19F NMR (CDCl3) δ 97.26 (d, J ) 6.10 Hz). IR (neat)
ν 3050, 3032, 2931, 2867, 1759, 1686. Anal. Calcd for
C16H19O4F3: C, 57.83; H, 5.76. Found: C, 58.11; H, 5.99.
(1′R )-3′-(Tr iflu or om e t h yl)-1′-p e n t yl-(Z)-2′-p r op e n yl
2-Meth oxya ceta te ((S)-(Z)-10c). Yield: 79%. 1H NMR
(CDCl3) δ 0.88 (3 H, t, J ) 6.83 Hz), 1.2-1.8 (8 H, m), 3.45 (3
H, m), 4.01 (1 H, d, J ) 16.36 Hz), 4.05 (1 H, d, J ) 16.61 Hz),
5.68 (1 H, ddq, J ) 1.22, 8.55, 11.97 Hz), 5.78-5.83 (1 H, m),
5.91 (1 H, dd, J ) 9.03, 11.96 Hz). 13C NMR (CDCl3) δ 13.82,
22.33, 24.28, 31.24, 34.19, 59.30, 69.67, 70.51, 119.40 (q, J )
34.7 Hz), 122.42 (q, J ) 271.5 Hz), 139.61 (q, J ) 4.9 Hz),
169.29. 19F NMR (CDCl3) δ 102.90 (d, J ) 9.50 Hz). IR (neat)
(2S,3S)-6-(Ben zyloxy)-3-(tr iflu or om eth yl)-2-m eth oxy-
4(E)-h exen -1-ol (a n ti-11a ). Yield: 68%. 1H NMR (CDCl3)
δ 2.99 (1 H, dquint, J ) 2.20, 9.52 Hz), 3.47 (3 H, s), 3.54 (1
H, dd, J ) 8.79, 13.91 Hz), 3.62-3.67 (1 H, m), 3.65 (1 H, ddd,
J ) 2.68, 6.35, 13.18 Hz), 4.05 (2 H, dd, J ) 1.47, 5.62 Hz),
4.50 (1 H, d, J ) 11.96 Hz), 4.52 (1 H, d, J ) 11.96 Hz), 5.73
(1 H, ddt, J ) 1.46, 9.52, 15.62 Hz), 5.87 (1 H, dt, J ) 5.61,
15.63 Hz), 7.2-7.4 (5 H, m). 13C NMR (CDCl3) δ 48.32 (q, J )
26.2 Hz), 59.27, 61.88 (q, J ) 1.2 Hz), 69.86, 72.13, 78.74 (q,
J ) 2.0 Hz), 122.26 (q, J ) 2.5 Hz), 126.20 (q, J ) 280.3 Hz),
127.72, 127.93, 128.40, 135.04, 137.89. 19F NMR (CDCl3) δ
93.90 (d, J ) 9.16 Hz). IR (neat) ν 3422, 3100, 3080, 3032,
2937, 2850. [R]24 ) +17.1 (c 0.5, CHCl3).
D
(2S*,3S*)-7-(Ben zyloxy)-3-(tr iflu or om eth yl)-2-m eth oxy-
4(E)-h ep ten -1-ol (a n ti-11b). Yield: 81%. 1H NMR (CDCl3)
δ 2.41 (2 H, tq, J ) 0.98, 6.59 Hz), 2.90 (1 H, dquint, J ) 2.20,
9.52 Hz), 3.47 (3 H, s), 3.53 (2 H, t, J ) 6.60 Hz), 3.51-3.56 (1
H, m), 3.62 (1 H, ddd, J ) 2.20, 6.10, 11.97 Hz), 4.51 (2 H, s),
5.54 (1 H, ddt, J ) 1.47, 9.77, 15.63 Hz), 5.76 (1 H, dt, J )
6.84, 15.62 Hz), 7.25-7.40 (5 H, m). 13C NMR (CDCl3) δ 33.00,
49.30 (q, J ) 26.0 Hz) 59.26, 62.04, 69.30, 72.81, 78.87 (q, J )
2.1 Hz), 120.98 (q, J ) 2.6 Hz), 126.32 (q, J ) 280.1 Hz),
127.60, 127.65, 128.35, 135.74, 138.18. 19F NMR (CDCl3) δ
93.73 (d, J ) 9.16 Hz). IR (neat) ν 3448, 3100, 3050, 3030,
2935, 2850.
ν 2950, 2935, 2900, 2850, 1762, 1677. [R]28 ) -6.4 (c 1.0,
D
CHCl3). Anal. Calcd for C12H19O3F3: C, 53.73; H, 7.14.
Found: C, 53.77; H, 7.35.
(1′R )-3′-(Tr iflu or om e t h yl)-1′-p e n t yl-(E )-2′-p r op e n yl
2-Meth oxya ceta te ((S)-(E)-10c). Yield: 77%. 1H NMR
(CDCl3) δ 0.8-0.9 (3 H, m), 1.2-1.4 (6 H, m), 1.6-1.8 (2 H,
m), 3.46 (3 H, s), 4.05 (1 H, d, J ) 16.36 Hz), 4.09 (1 H, d, J )
16.36 Hz), 5.46-5.50 (1 H, m), 5.81 (1 H, ddq, J ) 1.71, 6.34,
15.62 Hz), 6.32 (1 H, ddq, J ) 2.20, 5.61 15.87 Hz). 13C NMR
(CDCl3) δ 13.73, 22.28, 24.32, 31.22, 33.54, 59.22, 69.54, 72.07,
119.44 (q, J ) 269.4 Hz), 137.57 (q, J ) 6.4 Hz), 169.22. 19F
NMR (CDCl3) δ 97.30 (d, J ) 6.10 Hz). IR (neat) ν 2960, 2935,
(2S,3R)-6-(Ben zyloxy)-3-(tr iflu or om eth yl)-2-m eth oxy-
4(E)-h exen -1-ol (syn -11a ). Yield: 59%. 1H NMR (CDCl3) δ
3.19 (1 H, dquint, J ) 6.84, 9.28 Hz), 3.45 (3 H, s), 3.51 (1 H,
ddd, J ) 2.93, 5.62, 6.84 Hz), 3.57 (1 H, dd, J ) 1.71, 11.47
Hz), 4.04 (2 H, d, J ) 4.89 Hz), 4.51 (2 H, s), 5.57 (1 H, ddt, J
) 1.47, 9.76, 15.62 Hz), 5.90 (1 H, ddt, J ) 5.38, 15.38 Hz),
7.2-7.4 (5 H, m). 13C NMR (CDCl3) δ 48.29 (q, J ) 25.8 Hz),
58.03, 61.07 (q, J ) 1.7 Hz), 69.51, 72.21, 79.50 (q, J ) 1.5
Hz), 121.96 (q, J ) 2.7 Hz), 126.06 (q, J ) 280.4 Hz), 127.71,
127.74, 128.41, 134.94, 137.87. 19F NMR (CDCl3) δ 95.12 (d,
J ) 9.15 Hz). IR (neat) ν 3433, 3150, 3100, 3050, 2933, 2850.
2810, 1751. [R]28 ) +2.7 (c 0.9, CHCl3) (100% ee). Anal.
D
Calcd for C12H19O3F3: C, 53.73; H, 7.14. Found: C, 53.38; H,
7.36.
3′-(Tr iflu or om e t h yl)-1′-cycloh e xyl-(Z)-2′-p r op e n yl
2-Meth oxya ceta te (r a c-(Z)-10d ). Yield: 79%. 1H NMR
(CDCl3) δ 0.9-1.8 (11 H, m), 3.44 (3 H, s), 4.01 (1 H, d, J )
16.60 Hz), 4.05 (1 H, d, J ) 16.36 Hz), 5.60-5.67 (1 H, m),
5.72 (1 H, ddq, J ) 0.73, 8.55, 12.33 Hz), 5.87 (1 H, dd, J )
9.27, 12.09 Hz). 13C NMR (CDCl3) δ 25.67, 25.76, 25.99, 27.94,
28.18, 41.66, 59.29, 69.59, 73.71 (q, J ) 1.5 Hz), 120.41 (q, J
) 34.7 Hz), 122.35 (q, J ) 271.9 Hz), 137.93 (q, J ) 5.1 Hz).
19F NMR (CDCl3) δ 103.11 (d, J ) 9.16 Hz). IR (neat) ν 3010,
3000, 2932, 2856, 1762, 1676. Anal. Calcd for C13H19O3F3:
C, 55.71; H, 6.83. Found: C, 56.44; H, 7.31.
3′-(Tr iflu or om e t h yl)-1′-cycloh e xyl-(E )-2′-p r op e n yl
2-Meth oxya ceta te (r a c-(E)-10d ). Yield: 98%. 1H NMR
(CDCl3) δ 0.9-1.8 (11 H, m), 3.46 (3 H, s), 4.06 (1 H, d, J )
16.36 Hz), 4.10 (1 H, d, J ) 16.36 Hz), 5.28-5.33 (1 H, m),
5.79 (1 H, ddq, J ) 1.47, 6.35, 15.87 Hz), 6.32 (1 H, ddq, J )
2.20, 5.86, 15.87 Hz). 13C NMR (CDCl3) δ 25.55, 25.88, 27.90,
28.29, 41.21, 59.13, 69.42, 75.77, 120.14 (q, J ) 33.4 Hz), 122.5
(q, J ) 269.8 Hz), 136.34 (q, J ) 6.3 Hz), 169.19. 19F NMR
(CDCl3) δ 97.42 (d, J ) 7.63 Hz). IR (neat) ν 2980, 2933, 2857,
1762, 1685. Anal. Calcd for C13H19O3F3: C, 55.71; H, 6.83.
Found: C, 55.39; H, 6.86.
Gen er a l P r oced u r e of [3,3]-Ir ela n d -Cla isen Rea r -
r a n gem en t. To a 1,1,1,3,3,3-hexamethyldisilazane (0.078 mL,
0.37 mmol) in THF (2 mL) was added n-BuLi in hexane (1.6
M solution, 0.23 mL, 0.37 mmol) at -78 °C. The whole was
stirred at that temperature for 10 min, and then to this
mixture was added TMSCl (0.39 mL, 3.03 mmol), followed by
the addition of 3-(trifluoromethyl)allyl ester derivatives 10
(0.31 mmol). The mixture was stirred at that temperature for
30 min and then allowed to warm to room temperature and
stirred overnight. Saturated aqueous NaHCO3 was poured
into the mixture which was extracted with ether three times.
The combined aqueous layer was acidified and extracted with
ether. The organic layer was washed with brine, dried over
[R]27 ) +35.6 (c 0.2, CHCl3) (98% ee).
D
(2S*,3R)-7-(Ben zyloxy)-3-(tr iflu or om eth yl)-2-m eth oxy-
4(E)-h ep ten -1-ol (syn -11b). Yield: 61%. 1H NMR (CDCl3)
δ 2.35-2.42 (2 H, m), 3.08 (1 H, dquint, J ) 7.57, 9.12 Hz),
3.43 (3 H, s), 3.45 (1 H, dd, J ) 3.91, 4.88, 8.47 Hz), 3.51 (1 H,
dt, J ) 6.84, 9.03 Hz), 3.53 (1 H, dt, J ) 6.35, 9.28 Hz), 3.56
(1 H, dd, J ) 4.88, 11.96 Hz), 3.71 (1 H, dd, J ) 3.76, 11.97
Hz), 4.50 (2 H, s), 5.35 (1 H, ddt, J ) 1.46, 9.77, 15.39 Hz),
5.78 (1 H, dt, J ) 6.83, 15.38 Hz), 7.3-7.4 (5 H, m). 13C NMR
(CDCl3) δ 33.02, 49.26 (q, J ) 25.7 Hz), 57.93, 61.11 (q, J )
1.4 Hz), 68.88, 72.89, 79.58 (q, J ) 1.5 Hz), 121.70 (q, J ) 2.8
Hz), 125.73 (q, J ) 280.5 Hz), 127.63, 127.69, 128.34, 135.43,
138.02. 19F NMR (CDCl3) δ 94.69 (d, J ) 9.16 Hz). IR (neat)
ν 3448, 3080, 3050, 3032, 2935, 2863. Anal. Calcd for
C15H19O3F3: C, 60.37; H, 6.65. Found: C, 60.34; H, 7.12.
(2S ,3S )-3-(Tr iflu or om e t h yl)-2-m e t h oxy-4(E )-d e ce n -
1-ol (a n ti-11c). Yield: 75%. 1H NMR (CDCl3) δ 0.88 (3 H, t,
J ) 6.85 Hz), 1.2-1.3 (4 H, m), 1.38 (2 H, quint, J ) 7.32 Hz),
1.8-1.9 (1 H, m), 2.07 (2 H, dq, J ) 1.46, 7.08 Hz), 2.86 (1 H,
dquint, J ) 2.44, 9.52 Hz), 3.48 (3 H, s), 3.52-3.58 (1 H, m),
3.60-3.63 (1 H, m), 3.65 (1 H, dd, J ) 6.34, 9.52 Hz), 5.41 (1
H, ddt, J ) 1.47, 9.52, 15.38 Hz), 5.71 (1 H, dt, J ) 6.38, 15.38
Hz). 13C NMR (CDCl3) δ 13.97, 22.39, 28.54, 31.22, 32.53,
48.73 (q, J ) 1.5 Hz), 79.15 (q, J ) 2.1 Hz), 118.68 (q, J ) 2.5
Hz), 126.40 (q, J ) 280.1 Hz), 139.69. 19F NMR (CDCl3) δ
93.67 (d, J ) 9.16 Hz). IR (neat) ν 3424, 2950, 2931, 2850,
2800. [R]26 ) +16.1 (c 0.3, CHCl3). Anal. Calcd for
D
C12H21O2F3: C, 56.68; H, 8.32. Found: C, 56.54; H, 8.55.
(2S ,3R )-3-(Tr iflu or om e t h yl)-2-m e t h oxy-4(E )-d e ce n -
1-ol (syn -11c). Yield: 67%. 1H NMR (CDCl3) δ 0.88 (3 H, t,
J ) 6.83 Hz), 1.22-1.34 (4 H, m), 1.38 (2 H, quint, J ) 7.08
Hz), 1.9-2.0 (1 H, m), 2.06 (2 H, dq, J ) 1.47, 6.84 Hz), 3.08

Stereoselective Synthesis of Trifluoromethylated Compounds
J . Org. Chem., Vol. 62, No. 1, 1997 149
(1 H, dquint, J ) 7.32, 9.52 Hz), 3.45 (3 H, s), 3.47 (1 H, ddd,
J ) 2.93, 5.61, 7.08 Hz), 3.76 (1 H, dd, J ) 2.93, 11.97 Hz),
5.21 (1 H, ddt, J ) 1.47, 9.77, 15.38 Hz), 5.75 (1 H, dt, J )
6.84, 15.38 Hz). 13C NMR (CDCl3) δ 13.98, 22.39, 28.42, 31.20,
32.49, 48.62 (q, J ) 25.7 Hz), 58.04, 61.25 (q, J ) 1.6 Hz),
79.68 (q, J ) 1.5 Hz), 119.18 (q, J ) 2.7 Hz), 126.31 (q, J )
280.3 Hz), 139.55. 19F NMR (CDCl3) δ 94.84 (d, J ) 9.16 Hz).
IR (neat) ν 3450, 2970, 2933, 2880, 2850. [R]25D ) +36.6 ( 0.3,
CHCl3) (100% ee). Anal. Calcd for C12H21O2F3: C, 56.68; H,
8.32. Found: C, 56.58; H, 8.37.
(2S*,3S*)-5-Cycloh exyl-3-(tr iflu or om eth yl)-2-m eth oxy-
4(E)-p en ten -1-ol (a n ti-11d ). Yield: 80%. 1H NMR (CDCl3)
δ 1.0-1.3 (5 H, m), 1.5-1.8 (6 H, m), 1.9-2.1 (1 H, m), 2.83 (1
H, dquint, J ) 2.44, 9.77 Hz), 3.48 (3 H, s), 3.5-3.7 (3 H, m),
5.37 (1 H, ddd, J ) 1.23, 9.53, 15.39 Hz), 5.66 (1 H, dd, J )
6.83, 15.62 Hz). 13C NMR (CDCl3) δ 25.81, 26.01, 32.49, 32.57,
40.70, 48.80 (q, J ) 25.9 Hz), 59.39, 62.40 (q, J ) 1.5 Hz),
79.20 (q, J ) 1.9 Hz), 116.36 (q, J ) 2.6 Hz), 126.39 (q, J )
280.1 Hz), 145.21. 19F NMR (CDCl3) δ 93.66 (d, J ) 9.16 Hz).
IR (neat ) ν 3405, 2927, 2854. Anal. Calcd for C13H21O2F3:
C, 58.63; H, 7.95. Found: C, 58.88; H, 7.84.
4.08 (1 H, ddd, J ) 1.96, 4.89, 9.83 Hz). 13C NMR (CDCl3) δ
20.48, 27.10, 40.05 (q, J ) 24.6 Hz), 53.41, 56.96 (q, J ) 3.8
Hz), 59.51, 66.82 (q, J ) 1.9 Hz), 73.24 (q, J ) 1.4 Hz), 99.49,
125.97 (q, J ) 280.1 Hz). 19F NMR (CDCl3) δ 93.52 (d, J )
8.94 Hz). IR (neat) ν 2990, 2935, 2920, 2850.
Gen er a l P r oced u r e for th e Syn th esis of (2S,3S)-2-
(Tr iflu or om eth yl)-3-m eth oxybu tan e-1,4-diol (14). Meth od
A. To a suspension of Ag2O (excess, ca. 1.0 g) in ether (5 mL)
was added an ether solution of [2,3]-Wittig-rearranged product
(anti-9a , and anti-9c, 1.09 mmol) and methyl iodide (excess,
2.0 mL), and then the reaction mixture was stirred at 40 °C
overnight. The solution was cooled, filtered, and concentrated
in vacuo to give crude materials, which were treated with a
large excess amount of LiAlH4 (ca. 2 mmol) in THF at 0 °C.
The reaction mixture was stirred at room temperature for 2 h
and then quenched with 4 N KOH, and the usual workup gave
the crude [3,3]-Ireland-Claisen rearrangement product which
was purified by silica gel column chromatography to afford the
alcohol. The obtained material was treated with ozone in
methanol at -78 °C until the methyl ether was consumed.
Then, dimethyl sulfide (1.62 mL) was added into the reaction
mixture, which was stirred for 30 min at room temperature
and then evaporated. The resultant was treated with LiAlH4
(excess) in THF, and the usual workup afforded the diol.
Meth od B. [2,3]-Wittig rearrangement product, anti-9b (0.33
g, 1.00 mmol) was converted into the methyl ether (0.246 g,
0.710 mmol, 71% yield) by the same method as described in
method A. The obtained methyl ether was treated with ozone
in methanol at -78 °C, and the usual workup gave the
aldehyde. A solution of the aldehyde and LiAlH4 (ca. 0.076 g,
2 mmol) in THF was stirred for 2 h at room temperature, and
the usual workup gave the title compound (0.059 g, 0.314
mmol, 44% yield). 1H NMR (CDCl3) δ 2.3-2.4 (1 H, m), 2.54
(1 H, dtq, J ) 3.42, 6.83, 10.01 Hz), 2.9-3.2 (1 H, m), 3.50 (3
H, s), 3.69 (1 H, dd, J ) 4.03, 11.48 Hz), 3.72 (1 H, q, J ) 3.91
Hz), 3.87-3.94 (1 H, m), 3.99 (1 H, dd, J ) 6.83, 11.72 Hz).
13C NMR (CDCl3) δ 47.27 (q, J ) 24.0 Hz), 56.71 (q, J ) 3.3
Hz), 58.50, 61.51, 77.82 (q, J ) 2.3 Hz), 126.48 (q, J ) 280.5
Hz). 19F NMR (CDCl3) δ 94.26 (d, J ) 10.68 Hz). IR (neat) ν
(2S*,3R*)-5-Cycloh exyl-3-(tr iflu or om eth yl)-2-m eth oxy-
4(E)-p en ten -1-ol (syn -11d ). Yield: 64%. 1H NMR (CDCl3)
δ 1.0-1.4 (5 H, m), 1.6-1.8 (5 H, m), 1.9-2.1 (2 H, m), 3.04 (1
H, dquint, J ) 7.33, 9.28 Hz), 3.44 (3 H, s), 3.46 (1 H, ddd, J
) 2.93, 5.62, 7.08 Hz), 3.52-3.58 (1 H, m), 3.70-3.78 (1 H,
m), 5.17 (1 H, ddd, J ) 0.97, 9.52, 15.38 Hz), 5.70 (1 H, dd, J
) 6.83, 15.62 Hz). 13C NMR (CDCl3) δ 25.79, 25.99, 32.34,
32.48, 40.61, 48.66 (q, J ) 25.5 Hz), 58.05, 61.24 (q, J ) 1.6
Hz), 79.70 (q, J ) 1.6 Hz), 116.87 (q, J ) 2.7 Hz), 126.32 (q, J
) 280.2 Hz), 144.94. 19F NMR (CDCl3) δ 94.82 (d, J ) 9.16
Hz). IR (neat) ν 3418, 2927, 2853. Anal. Calcd for C13H21
O2F3: C, 58.63; H, 7.95. Found: C, 58.41; H, 7.95.
-
P r oced u r e for Deter m in a tion of Ster eoch em istr y. To
a solution of anti-9c (0.856 g, 3.19 mmol) in CH2Cl2 (30 mL)
was added ethyl vinyl ether (0.407 mL, 4.25 mmol) and a
catalytic amount of pyridinium p-toluenesulfonate at 0 °C, and
the reaction mixture was allowed to warm to room tempera-
ture and stirred for 2 h. Then, saturated NaHCO3 was poured
into the reaction mixture, and the whole was extracted with
CH2Cl2. The organic layer was washed, dried over anhydrous
MgSO4, and evaporated in vacuo. The resultant crude materi-
als were added into a solution of LiAlH4 (0.065 g, 1.70 mmol)
in THF (30 mL) at 0 °C and stirred for 1 h, and then the
reaction mixture was quenched with 4 N KOH. After usual
workup, a solution of the crude materials and NaH (0.227 g,
5.67 mmol) in THF (30 mL) was stirred at 0 °C for 30 min,
followed by the addition of methyl iodide (0.353 mL, 5.67
mmol). After stirring for 3 h at room temperature, the reaction
was quenched with aqueous NaHCO3, and the mixture was
extracted with ether three times. The combined organic layers
were washed with brine, dried over anhydrous sodium sulfate,
and then concentrated in vacuo to afford the crude methyl
ether which was treated with a catalytic amount of TsOH in
methanol (20 mL), affording the alcohol 12. This compound
was dissolved in MeOH (10 mL) and treated with ozone at -78
°C until the alcohol 12 was consumed. Dimethyl sulfide (0.425
mL) was added into the reaction mixture, which was stirred
at that temperature, and then allowed to warm to room
temperature and concentrated in vacuo to give the crude oil.
The crude materials were immediately reduced with LiAlH4
(0.132 g, 3.48 mmol) in THF (20 mL) at 0 °C, and the usual
workup afforded the corresponding diol, which was treated
with dimethoxypropane (0.199 mL, 1.62 mmol)/acetone (5 mL)/
pyridinium p-toluenesulfonate (cat.). The reaction mixture
was stirred at room temperature for 3 h and then quenched
with saturated NaHCO3, and the whole was concentrated in
vacuo, extracted with ether, dried over anhydrous MgSO4,
filtered, and evaporated to furnish the crude acetonide.
Purification by silica gel column chromatography gave
acetonide as a yellow oil (0.033 g, 0.146 mmol).
3385, 2941, 2930, 2900. [R]20 ) -6.4 (c 0.6, CHCl3). Anal.
D
Calcd for C6H11O3F3: C, 38.30; H, 5.89. Found: C, 38.62; H,
6.08. Racemic rearranged products (anti-9d and anti-9e) were
converted into (2S*,3S*)-2-(Trifluoromethyl)-3-methoxybutane-
1,4-diol according to method A.
(2R)-2-(Tr iflu or om eth yl)-1-[(4-m eth ylp h en yl)su fen yl]-
n on en e (17). Meth od A. To a solution of LiAlH4 (0.166 g,
4.37 mmol) in THF (5 mL) was added anti-9c (0.195 g, 0.729
mmol) at 0 °C and stirred for 1 h at room temperature. The
reaction mixture was quenched with 4 N KOH, and the organic
layer was dried over anhydrous MgSO4 and concentrated in
vacuo. Purification of the resultant crude materials by silica
gel column chromatography gave the corresponding diol (0.134
g, 0.561 mmol), which was treated with Raney Ni (excess)/H2
in ethanol (10 mL) under 10 atm. The reaction mixture was
stirred overnight and then filtered, the filtrate was evaporated,
and the residue was purified by silica gel column chromatog-
raphy to furnish the saturated diol (0.136 g, 0.561 mmol). To
a suspension of Pb(OAc)4 (0.760 mmol, 0.337 g) in CH2Cl2 (20
mL) was added slowly the obtained compound at 0 °C under
nitrogen atmosphere. The reaction mixture was stirred for
several hours, filtered through Florisil, and washed with ethyl
acetate. The filtrate was concentrated to give the crude
materials, which were treated immediately with LiAlH4 (0.064
g, 1.68 mmol) in THF (5 mL), and the usual workup gave the
alcohol ((S)-16, [R]21D ) +3.1 (c 0.6, CHCl3).). To a solution of
this compound and CBr4 (0.942 g, 2.84 mmol) in CH2Cl2 (15
mL) was added PPh3 (0.742 g, 2.83 mmol) at 0 °C, and the
reaction mixture was allowed to warm to room temperature
and stirred for 2 h. Then a large amount of hexane was added
into the reaction mixture which was filtered, and concentrated
in vacuo. The resultant oil was passed through silica gel, and
the obtained crude materials were treated with p-toluenethiol
(0.248 g, 2.0 mmol) and sodium hydride (0.080 g, 2.0 mmol)
at 0 °C. The reaction mixture was stirred at room temperature
for 2 h and then poured into 3 N HCl, extracted with ether,
washed with brine, dried over anhydrous MgSO4, and evapo-
(4S,5S)-5-(Tr iflu or om et h yl)-4-(m et h oxym et h yl)-2,2-
d im eth yl-1,3-d ioxa cycloh exa n e (13). Yield: 5%. 1H NMR
(CDCl3) δ 1.41 (3 H, s), 1.44 (3 H, s), 2.71 (1 H, m), 3.41 (3 H,
s), 3.52 (1 H, dd, J ) 4.88, 10.98 Hz), 3.59 (1 H, m), 3.90 (1 H,
dd, J ) 7.08, 12.21 Hz), 3.96 (1 H, dd, J ) 5.86, 11.96 Hz),

150 J . Org. Chem., Vol. 62, No. 1, 1997
Konno et al.
rated. The residue was purified by silica gel column chroma-
tography to give 17 (0.022 g, 0.069 mmol, 9% yield). Meth od
B. The sulfoxide 18 (0.110 g, 0.418 mmol) was treated with
LiAlH4 (0.022 g, 0.585 mmol) in THF (3 mL) at 0 °C, and the
mixture was stirred at room temperature for 1 h. The reaction
was quenched with 4 N aqueous KOH and the usual workup
gave the alcohol (0.095 g, 0.360 mmol). To a solution of oxalyl
chloride (0.138 mL, 1.61 mmol) in CH2Cl2 (10 mL) at -78 °C
was added dimethyl sulfoxide (0.17 mL) in CH2Cl2 (3 mL).
After the mixture was stirred for 10 min, a CH2Cl2 solution of
the alcohol obtained above was introduced and the resulting
mixture stirred for 30 min. To this was added triethylamine
(0.646 mL). The mixture was further stirred at -78 °C for 2
h and quenched with 20 mL of saturated aqueous NH4Cl. This
mixture was extracted with CH2Cl2. The combined organic
extracts were dried over anhydrous MgSO4, filtered, and
concentrated in vacuo. Purification of the resultant crude
materials was carried out by silica gel column chromatography
to afford the corresponding aldehyde. To a suspension of
n-pentyltriphenylphosphonium iodide (0.46 g, 1 mmol) in THF
(5 mL) was added dropwise n-BuLi/hexane (0.625 mL, 1 mmol)
at 0 °C, and thw whole was stirred for 30 min at that
temperature. To this was added a THF solution of the above
aldehyde. After stirring for 1 h at 0 °C, the reaction was
diluted with a large amount of hexane (ca. 20 mL), and the
mixture was filtered and concentrated in vacuo. The resulting
oil was purified by silica gel column chromatography to afford
the desired materials as a ca. 81:19 mixture of E and Z forms.
To a suspension of 10% Pd/C (0.00524 g) in ethanol (5 mmol)
was dissolved the obtained sulfide, and the reaction mixture
was stirred under 10 atm hydrogen pressure for 24 h. The
mixture was filtered and concentrated in vacuo to give crude
materials, which were purified by silica gel column chroma-
tography to obtain the desired compound (0.073 g, 0.232 mmol,
59% yield). 1H NMR (CDCl3) δ 0.88 (3 H, t, J ) 6.85 Hz), 1.20-
1.40 (10 H, m), 1.65-1.70 (2 H, m), 2.15-2.25 (1 H, m), 2.33
(3 H, s), 2.78 (1 H, dd, J ) 8.79, 13.67 Hz), 3.22 (1 H, dd, J )
4.03, 13.55 Hz), 7.10-7.30 (4 H, m). 13C NMR (CDCl3) δ 14.06,
20.99, 22.61, 26.57, 27.19 (q, J ) 2.1 Hz), 28.98, 29.50, 31.75,
33.15 (q, J ) 2.9 Hz), 42.67 (q, J ) 24.9 Hz), 127.73 (q, J )
281.1 Hz), 129.89, 130.76, 131.42, 136.99. 19F NMR (CDCl3)
δ 91.80 (d, J ) 9.15 Hz). IR (neat) ν 3150, 3000, 2960, 2926,
ethanol (15 mL) was stirred at room temperature under 10
atm hydrogen for 2 days. The reaction mixture was filtered,
and the filtrate was concentrated in vacuo to afford crude
materials which were purified by silica gel column chroma-
tography to give the saturated molecules (0.145 g, 0.545 mmol).
To this compound in CH2Cl2 (3 mL) was added a BBr3 solution
in CH2Cl2 (1.0 M solution, 2.0 mL, 2.0 mmol) at -20 °C, and
the whole was stirred at that temperature for several hours.
Then the reaction mixture was poured into 1 N HCl, and
extracted with CH2Cl2, dried over anhydrous MgSO4, and
evaporated to afford the diol. To a suspension of Pb(OAc)4
(0.443 g) in CH2Cl2 (50 mL) was added the diol in CH2Cl2 (15
mL) over 30 min at 0 °C in nitrogen atmosphere. The reaction
mixture was stirred at that temperature for several hours and
then passed through florisil. The resulting solution was
concentrated in vacuo to afford the crude materials which were
purified by silica gel column chromatography to give the
desired alcohol (0.090 g, 0.424 mmol). Yield: 33%. 1H NMR
(CDCl3) δ 0.88 (3 H, t, J ) 7.08 Hz), 1.2-1.7 (12 H, m), 2.0-
2.1 (1 H, m), 2.15-2.25 (1 H, m), 3.50-70 (2 H, m). 13C NMR
(CDCl3) δ 14.52, 23.09, 25.12 (q, J ) 2.3 Hz), 27.31, 29.51,
30.00, 32.23, 45.89 (q, J ) 23.8 Hz), 60.33 (q, J ) 3.1 Hz),
128.46 (q, J ) 280.6 Hz). 19F NMR (CDCl3) δ 92.62 (d, J )
9.15 Hz). IR (neat) ν 3346, 2950, 2926, 2900. [R]24D ) -1.0 (c
0.7, CHCl3).
(2R,3S)-2-(Tr iflu or om et h yl)-3-m et h oxyb u t a n -1,4-d iol
(20). syn-11a and syn-11c were converted into the title
compound by the similar method described in the preparation
of (2S,3S)-2-(trifluoromethyl)-3-methoxybutane-1,4-diol. 1H
NMR (CDCl3) δ 2.40-2.56 (1 H, m), 2.62-2.72 (1 H, m), 2.76-
2.88 (1 H, m) 3.46 (3 H, s) 3.66 (1 H, dt, J ) 3.79, 5.62 Hz)
3.74-3.80 (1 H, m) 3.78-3.96 (2 H, m). 13C NMR (CDCl3) δ
46.74 (q, J ) 23.5 Hz) 56.99 (q, J ) 3.2 Hz) 57.82, 60.48 (q, J
) 1.6 Hz) 78.08 (q, J ) 1.8 Hz) 126.49 (q, J ) 281.0 Hz). 19F
NMR (CDCl3) δ 96.27 (d, J ) 10.69 Hz). IR (neat) ν 3384,
2942, 2930, 2838. [R]24 ) +9.7 (c 0.6, CHCl3).
D
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
spectra of compounds (37 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
2857. [R]23 ) -71.6 (c 0.7, CHCl3) (>98% ee).
D
(2R)-2-(Tr iflu or om eth yl)n on a n -1-ol ((R)-16). A solution
of syn-11c (0.250 g, 0.947 mmol) and Raney Ni (excess) in
J O961246I