Michael addition of organocopper species to 3-[(E)-4,4,4-trifluorobut-2-enoyl]oxazolidin-2-ones

Article abstract of DOI:10.1016/S0022-1139(99)00034-2

Investigation of Michael addition has been carried out using versatile organomagnesium or -lithium reagents in the presence of copper(I) species towards chiral 3-[(E)-4,4,4-trifluorobut-2-enoyl]oxazolidin-2-ones, and it was demonstrated that this route enabled us to successfully construct optically active molecules with a CF₃ moiety at the chiral center in good yields as well as the high level of diastereofacial selectivity.

Full text of DOI:10.1016/S0022-1139(99)00034-2

Journal of Fluorine Chemistry 97 (1999) 91±96
Michael addition of organocopper species to
3-[(E)-4,4,4-tri¯uorobut-2-enoyl]oxazolidin-2-ones
Takashi Yamazakia,*, Noriyasu Shinoharaa, Tomoya Kitazumea, Shoichi Satob
aDepartment of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-Ku, Yokohama 226-8501, Japan
bRigaku Corporation, 3-9-12, Matsubara-Cho, Akishima, Tokyo 196-8666, Japan
Received 24 October 1998; received in revised form 7 November 1998; accepted 9 November 1998
Dedicated to Prof. Yoshiro Kobayashi on the occasion of his 75th birthday
Abstract
Investigation of Michael addition has been carried out using versatile organomagnesium or -lithium reagents in the presence of copper(I)
species towards chiral 3-[(E)-4,4,4-tri¯uorobut-2-enoyl]oxazolidin-2-ones, and it was demonstrated that this route enabled us to
successfully construct optically active molecules with a CF3 moiety at the chiral center in good yields as well as the high level of
diastereofacial selectivity. # 1999 Elsevier Science S.A. All rights reserved.
Keywords: Michael addition; Organocopper reagents; Tri¯uoromethyl group; Oxazolidin-2-one
1. Introduction
conveniently applicable to reactions with a wide variety of
enolates to furnish the corresponding 1,4-adducts in good
chemical yields as well as with high levels of diastereos-
electivities. However, no adducts were obtained by the
conjugate addition of enolates towards the oxazolidinone-
based acceptor 2 known as powerful chiral auxirialies, while
the opposite combination like acylated oxazolidinone eno-
lates [31±34] with 1a smoothly formed the corresponding
1,4-addition products [35,36]. On the other hand, although
the conjugate addition of anisylmagnesium bromide towards
1a failed irrespective of the presence of catalysts, the
oxazolidinone-containing acceptor 2 was found to success-
fully construct a new carbon±carbon bond with organomag-
nesium or -lithium reagents in a stereoselective fashion. We
would like to report herein Michael addition of these
organometallic nucleophiles towards chiral oxazolidin-2-
ones 4 and 5 in the presence of copper(I) species.
Stereoselective carbon±carbon bond formation is one of
the most important processes in organic syntheses. Michael
reaction [1±3] is among such a class of reactions known as
conjugate additions of nucleophiles to ole®ns activated by
various functionalities like carbonyl, sulfoxide, sulfone,
cyano, nitro groups and so on.
We have been interested in development of novel routes
for the preparation of optically active ¯uorine-containing
materials with special attention to the corresponding tri-
¯uoromethylated molecules [4±7], since they are not always
accessible in an easy fashion via the conventional ¯uorina-
tion techniques [8,9]1 or the direct entry of a CF3 group with
appropriate reagents [11,12]. Such dif®culties prompted us
to have concentrated our study on Michael additions with
CF3-containing acceptors [13±22] thus far [23±26] as the
alternative pathway to stereoselectively as well as ef®ciently
construct materials with this moiety.
2. Results and discussion
For example, as shown in Scheme 1, ethyl (E)-4,4,4-
tri¯uorobut-2-enoate 1a [26±30] and (E)-3,3,3-tri¯uoro-
prop-1-en-1-yl p-tolyl sulfoxide 1b [24] were found to be
At ®rst, the unsubstituted oxazolidinone acceptor 3 was
treated with p-anisylmagnesium bromide (R: p-CH3O±
C6H4±), but 3 was recovered in 37% yield without any
detectable formation of the desired 1,4-adduct (Entry 1 in
Table 1). However, addition of CuBrÁSMe2 [37±40] to this
system drastically changed the reaction course, and 6a was
obtained as a sole product in 93% yield (Entry 2). This
*Corresponding author. Tel.: +81-45-924-5755; fax: +81-45-924-5780;
e-mail: tyamazak@bio.titech.ac.jp
1For the recently reported milder fluorination method of sulfur-based
functionality to the corresponding trifluoromethyl group, see, Ref. [10].
0022-1139/99/$ ± see front matter # 1999 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 9 9 ) 0 0 0 3 4 - 2

92
T. Yamazaki et al. / Journal of Fluorine Chemistry 97 (1999) 91±96
Scheme 1.
condition was found to be similarly effective to the corre-
sponding chiral acceptors 4 and 5 (Entries 3 and 4). The
major diastereomer of 8a was subjected to X-ray crystal-
lographic analysis, and determination of the structure led us
to the mechanistic assumption that the anisyl group
approached from the si face of the conformationally ®xed
a,b-unsaturated carbonyl part possibly by the metal-assisted
intramolecular bidentate chelation (Figs. 1 and 2). On the
basis of precedent work by Evans et al. [31±34], reactions
Fig. 1.
might alternatively proceed via the non-chelation confor-
mation for excluding the unfavorable dipole repulsion
between two carbonyl groups, while attack from the less
hindered upper face should consequently cause the opposite
diastereomer selection.
Table 1
CuBrÁSMe2-catalyzed Grigard reaction with acceptors 3, 4, and 5a
Entry
Rc
R0
Reaction time (h)
Product
Yieldb (%)
de (%)
6, 7, 8
9
1d
2
p-An
p-An
p-An
p-An
p-An
Ph
H
3.0
1.0
1.0
1.0
1.0
1.0
1.0
2.0
4.0
3.0
3.0
1.0
1.0
1.0
3.0
2.0
6a
6a
7a
8a
7a
7b
7b
7b
7c
7c
7c
7c
7c
7d
7e
7f
0 (37)
93
0
0
0
0
0
0
0
0
±
±
H
3
Ph
Bn
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
94
62
40
90
50
60
72
45
60
44
6
4
5e
Quant
Quant
Quant
Quant
Quant
36
6
7e
8e
9
Ph
Ph
Me
64
0
10f
11f
12f
13f
14
15
16
Me
92
Me
26
72
30
34
0
Me
Me
54
42
6
Vinyl
i-Bu
Allyl
80
9g
12g
>98
h
80
68
±
±
h
a The reaction was conducted with 3 equiv of a Grignard reagent (GR) and CuBrÁSMe2 (CBDS). See Section 4 in detail.
b Isolated yield. In the parenthesis was shown the recovered yield of an acceptor determined by 19F NMR.
c p-An: p-MeO±C6H4 .
d Reaction was performed in the absence of CBDS.
e 3 equiv of MgBr2 (Entries 5 and 7) or LiBr (Entry 8) were added.
f Equivalents of GR/CBDS used were 1.5/1.5 (Entry 10), 6.0/6.0 (Entry 11), 3.0/1.5 (Entry 12), and 4.5/1.5 (Entry 13).
g Not isolated and determined by 19F NMR.
h Not determined.

T. Yamazaki et al. / Journal of Fluorine Chemistry 97 (1999) 91±96
93
proportional to their amounts (Entries 10!9!11; 1.5!
3.0!6.0 equiv, 92%!36%!26% yields, respectively)
with the opposite trend observed for 9 (0%!64%!72%
yields, respectively). Moreover, comparison between
Entries 10, 12 and 13 clari®ed that approximately 30% of
9 was formed under conditions when two- or threefold
excess amounts of MeMgBr were used with respect to
CuBrÁSMe2. The best result was obtained for the system
depicted in Entry 10 using 1.5 equiv of MeMgBr and
CuBrÁSMe2 to give 7c in 90% yield with 60% de. Although
the vinyl Grignard reagent also exhibited the excellent
diastereocontrol (80% yield, >98% de; Entry 14), i-Bu or
allyl Grignard reagents only led to the preferential forma-
tion of the de¯uorinated product 9 (Entries 15 and 16).
We have also studied the reactivity of 4 towards Me- or n-
BuLi-based cuprates, which was tabulated in Table 2. In the
case of introduction of a methyl group, the Gilman reagent
reacted sluggishly (Entry 6), and higher order cuprate in the
presence of BF3ÁOEt2 suffered from the formation of an
appreciable amount of byproduct 9 (Entry 7). Methylcopper
(MeLi:CuIˆ1:1) gave similar results to the case of cyano-
cuprate MeCu(CN)Li, while addition of MgBr2 or BF3ÁOEt2
realized the excellent diastereofacial selection or good total
recovery, respectively (Entries 1±5). It is interesting to note
that MeLi-based reaction conveniently suppressed the for-
mation of 9 which was obtained sometimes as the main
product for the reaction of MeMgBr±CuBrÁSMe2. For entry
of an n-Bu moiety, the highest yield was recorded by use of
2.0 equiv of n-BuCu/LiI (Entry 9), while, in spite of some-
Fig. 2.
The acceptor 4 was preferable to 5 in terms of diaster-
eoselectivity (Entries 3 and 4). Further investigation was
carried out on the effect of Lewis acids as additives for
aiming at improvement of the de values, and MgBr2 was
revealed to remarkably increase the de up to 90% (Entry 5).
When the phenyl Grignard reagent was used, LiBr was
found to be more effective than the case of MgBr2 and the
1,4-adduct 7b was afforded quantitatively with 72% de
(Entries 6±8). Attainment of better diastereofacial selection
by the addition of Lewis acids strongly supported the above
hypothesis that oxazolidinone acceptors would possess an
intramolecularly chelated cyclic structure in solution.
On the other hand, MeMgBr furnished the adduct 7c only
in 36% yield along with the unexpected terminally di¯uori-
nated b,g-unsaturated material 9 in 64% yield (Entry 9).
Product distribution between 7c and 9 was signi®cantly
dependent on the equivalent of MeMgBr and CuBrÁSMe2
employed, and the yield of 7c seemed to be inversely
Table 2
Reactions of various lithium cuprates with the acceptor 4
Entry
Cuprate (equiv)
Time (h)
Product
Yielda (%)
de of 7 (%)
7
9
1
2
3b
4c
5
MeCu/LiI (2.0)
1.0
2.0
6.5
4.5
3.0
2.0
1.0
4.0
4.0
3.0
2.0
4.0
7c
7c
7c
7c
7c
7c
7c
7g
7g
7g
7g
7g
64
0
0
0
0
0
0
90
88
MeCu/LiI (3.0)
66
MeCu/LiI (3.0)
MeCu/LiI (3.0)
68
>98
90
63 (37)
70 (4)
26
MeCu(CN)Li (3.0)
Me2CuLi/LiI (3.0)
Me3CuLi2/LiI (3.0)
n-BuCu/LiI (3.0)
n-BuCu/LiI (2.0)
n-BuCu/LiI (2.0)
n-BuCu/LiI (2.0)
n-BuCu/LiI (3.0)
84
e
±
6
7c
8
48 (7)
58
33
42
6
94
66
72
70
87
74
9
86
10b
11d
12c
58
8
65
63
0
26
a Isolated yield. In the parenthesis was shown the recovered yield of an acceptor determined by 19F NMR.
b 3 equiv of MgBr2 was added.
c 3 equiv of BF3ÁOEt2 was added.
d 3 equiv of LiBr was added.
e Not determined.

94
T. Yamazaki et al. / Journal of Fluorine Chemistry 97 (1999) 91±96
what lower yield, the better stereo- and product-selectivity
were realized by LiBr which furnished 7 in 87% de and
successfully suppressed formation of the byproduct 9 (Entry
12).
omethane were purchased from Kanto Chemical, and used
as they were. All other reagents were obtained from com-
mercial suppliers and were used without puri®cation unless
otherwise noted.
Yamamoto and co-workers [41] reported the single elec-
tron transfer (SET) ability of organocopper species in the
order of MeCu(CN)Li<MeCu<Me2CuLi<Me3CuLi2, and
the easier SET occurs and the larger amount of a reduced
material (H introduction instead of a Me group) is obtained.
In Table 2, it was already described that MeCu(CN)Li and
MeCu almost cleanly furnished 7, while only lower yields
were obtained for reactions with Me2CuLi or Me3CuLi2,
with the unacceptable degree of total recovery of ¯uorine-
containing materials or with the formation of di¯uorinated
byproduct, recpectively (Entries 5, 2, 6, and 7, respectively).
Suppose that the SET mechanism is responsible for these
side reactions, our results would be consistently understood
in a similar manner. Thus, Michael products 6±8 seemed to
be afforded as the result of nucleophilic addition of copper
species followed by reductive elimination of a migrating
group, and the electron-transfer process would be respon-
sible for the formation of 9 by way of a,b-dianionic species
postulated by Yamamoto and co-workers [41].
Although the actual species have not yet been con®rmed
for Grignard reagents in the presence of copper catalysts, an
analogous tendency was observed when we assumed
Grignard reagents behave similarly to the corresponding
organolithiums. Entries 10, 12, and 13 in Table 1 showed
the results for MeCu, Me2CuMgBr, and Me3Cu(MgBr)2 and
the yield of 7c decreased in this order (92%!54%!42%)
with increasing yields of 9 (0%!30%!34%). Moreover,
Yamamoto et al. [42] also pointed out that the order of
elctron-donation ability is methallylꢀn-butyl>vinyl by the
photoelectron spectra of organotins with these groups
instead of the corresponding organocopper species due to
their instability, which nicely applied for qualitative eluci-
dation of the exclusive formation of 9 when allyl or i-butyl
Grignard reagents were used.
1H NMR were recorded with Varian VXR-500 or
GEMINI 200 (500 or 200 MHz, respectively), and
13C NMR spectra were recorded with a GEMINI 200
(50 MHz) in CDCl3 unless otherwise noted. Chemical shifts
were recorded in parts per million (ppm), down®eld from
internal tetramethylsilane. 19F NMR spectra were recorded
with a Varian VXR-500 (470 MHz) in CDCl3 unless other-
wise noted and chemical shifts were reported in ppm down-
®eld from external CF3CO2H. Infrared (IR) spectra were
obtained on a Perkin-Elmer FT-IR 1650 spectrometer and
all spectra were reported in wave numbers (cm 1), with the
1
reference at the 1601.4 cm absorption of a polystyrene
®lm. Optical rotations were measured on a JASCO DIP-
1000 digital polarimeter. Speci®c rotations, [ꢀ]D, were
reported in degree and the concentration (c) was given in
gram per 100 ml of the indicated solvent.
Because diastereomeric pairs obtained usually were inse-
parable or dif®cult to be separated, puri®cation furnished
their mixture and thus only major products were shown
unless otherwise noted.
General procedure for 4-substituted 3-[(E)-4,4,4-tri¯uor-
obut-2-enoyl]oxazolidin-2-one. To a dry two-necked ¯ask
equipped with a rubber septum and placed under a nitrogen
atmosphere, THF (100 ml) and 73.6 mmol of (R)-4-phenyl-
or benzyloxazolidin-2-one were added. To this solution was
added 48.3 ml (77.2 mmol; 1.6 M, 1.05 equiv) of n-BuLi at
568C, and the mixture was stirred for 30 min. In a separate
¯ask, 13.0 g (73.6 mmol) of (E)-4,4,4-tri¯uorobut-2-enoyl
chloride was dissolved in 100 ml of THF and cooled to
568C. The lithiated oxazolidinone was then added via a
syringe, and stirred at 568C for 6 h. The reaction was
quenched with a sat. NH4Cl solution (20 ml), and the
volatiles were evaporated. To the resulting suspension
Et2O (40 ml) and H2O (20 ml) were added. The aqueous
layer was separated, and the organic layer was washed with
a sat. NaHCO3 solution and brine, which was further dried
over anhydrous MgSO4. After ®ltration, the solvent was
removed under vacuum and the resultant crude product was
chromatographed on a silica gel (hexane:ethyl acetateˆ1:1)
to yield the desired compound.
3. Conclusion
As shown above, we have succeeded in construction of
optically active molecules with a CF3 moiety at the chiral
center in good yields as well as the high level of diaster-
eofacial selectivity by way of Michael addition reactions of
organometallic reagents in the presence of copper(I) species
towards3-[(E)-4,4,4-tri¯uorobut-2-enoyl]oxazolidin-2-ones.
(S)-3-[(E)-4,4,4-Tri¯uorobut-2-enoyl]-4-phenyloxazoli-
20
din-2-one (4). Yield 77%. ‰ꢀŠ
106.248 (c 0.50, CHCl3).
D
1H NMR ꢁ 4.37 (1H, dd, Jˆ3.94, 9.01 Hz), 4.77 (1H, t,
Jˆ8.83 Hz), 5.50 (1H, dd, Jˆ3.83, 8.63 Hz), 6.80 (1H, qd,
Jˆ6.63, 15.55 Hz), 7.30±7.43 (5H, m), 7.93 (1H, qd,
Jˆ2.02, 15.54 Hz). 13C NMR ꢁ 57.84, 70.33, 122.08 (q,
Jˆ269.9 Hz), 126.07, 127.48 (q, Jˆ6.2 Hz), 129.13,
129.36, 132.19 (q, Jˆ35.6 Hz), 138.04, 153.22, 162.10.
4. Experimental
19F NMR ꢁ 13.3 (d, Jˆ6.2 Hz). IR (KBr) ꢂ 3108, 3055,
4.1. General
1
2923, 1784, 1698, 1669, 738, 700, 650 cm
(S)-4-Benzyl-3-[(E)-4,4,4-tri¯uorobut-2-enoyl]oxazoli-
.
Alkyllithiums and Grignard reagents were titrated prior to
use. Dehydrated diethyl ether, tetrahydrofuran, and dichlor-
24
D
din-2-one (5). Yield 89%. ‰ꢀŠ ‡67.808 (c 0.83, CHCl3).

T. Yamazaki et al. / Journal of Fluorine Chemistry 97 (1999) 91±96
95
1H NMR ꢁ 2.82 (1H, dd, Jˆ9.53, 13.36 Hz), 3.35 (1H, m),
4.23 (1H, dd, Jˆ4.00, 9.25 Hz), 4.29 (1H, ddd, Jˆ0.67,
6.95, 9.15 Hz), 4.76 (1H, m), 6.93 (1H, qd, Jˆ6.62,
15.57 Hz), 7.19±7.35 (5H, m), 7.92 (1H, qd, Jˆ2.02,
15.57 Hz). 13C NMR ꢁ 37.67, 55.37, 66.60, 122.17 (q,
Jˆ270.0 Hz), 127.62, 127.68 (q, Jˆ6.1 Hz), 129.14,
129.42, 132.05 (q, Jˆ35.7 Hz), 134.77, 152.99, 162.56.
(q, Jˆ2.2 Hz), 37.23, 44.59 (q, Jˆ27.7 Hz), 54.94, 55.21,
66.12,114.10,126.00(q,Jˆ2.0 Hz),126.44(q,Jˆ256.5 Hz),
127.36, 128.89, 130.30, 134.66, 153.31, 159.64, 169.56.
19F NMR ꢁ 8.51 (d, Jˆ8.4 Hz). IR (KBr) ꢂ 3019, 2936,
1
.
1781, 1706, 1516, 1265, 1160, 1104, 760, 704 cm
(S)-3-[(R)-4,4,4-Tri¯uoro-3-phenylbutanoyl]-4-phenyloxa-
23
D
zolidin-2-one(7b). Yieldquant. de50%. ‰ꢀŠ
73.528(c0.57,
19F NMR ꢁ 13.4 (d, Jˆ6.9 Hz). Ir (KBr) ꢂ 3108, 3065,
CHCl3).1H NMRꢁ3.40±3.57(1H,m),3.78±4.12(2H,m),4.19
(1H, dd, Jˆ3.82, 8.87 Hz), 4.68 (1H, t, Jˆ8.81 Hz), 5.38 (1H,
dd, Jˆ3.94, 8.61 Hz), 6.88±6.93 (2H, m), 7.14±7.37 (8H, m).
13C NMR ꢁ 34.94 (q, Jˆ2.3 Hz), 45.42 (q, Jˆ27.9 Hz), 57.61,
70.03,125.24,125.87,126.29(q,Jˆ265.0 Hz),128.43,128.47,
128.69, 129.10, 129.14, 129.27, 138.07, 138.50, 153.59,
1
3030, 2924, 1786, 1695, 1668, 761, 736, 702, 629 cm
.
General procedure for conjugate additions of the orga-
nocopper reagents from Grignard reagents. An appropriate
Grignard reagent (6.0 mmol) was added to a solution of
CuBrÁSMe2 complex (1.23 g, 6.0 mmol) in THF (14 ml) and
Me2S (7 ml) at 568C. The resultant yellow±green mixture
was stirred for 30 min and a solution of an acceptor
(2.0 mmol) in THF (8 ml) was added dropwise at 568C,
and the mixture was stirred at that temperature for a required
time. The mixture was quenched with a sat. NH4Cl solution,
and a 5% aqueous ammonia solution was then added. The
organic layer was separated and the blue aqueous solution
was then added. The organic layer was separated and the
blue aqueous solution was extracted with Et2O. The usual
work-up and puri®cation by silica gel column chromato-
graphy or recrystallization afforded the desired product.
3-[4,4,4-Tri¯uoro-3-(4-methoxyphenyl)butanoyl]oxazo-
lidin-2-one (6a). Yield 93%. 1H NMR ꢁ 3.47 (1H, dd,
Jˆ4.13, 17.82 Hz), 3.75 (1H, dd, Jˆ9.77, 18.07 Hz), 3.80
(3H, s), 3.90 (1H, ddd, Jˆ6.84, 9.28, 14.40 Hz), 3.97 (1H,
ddd, Jˆ7.08, 9.28, 14.52 Hz), 4.03 (1H, dqd, Jˆ4.15, 9.52,
9.53 Hz), 4.37 (1H, td, Jˆ7.08, 9.04 Hz), 4.40 (1H, td,
Jˆ6.92, 9.03 Hz), 6.86±6.90 (2H, m), 7.30 (2H, d,
Jˆ8.79 Hz). 13C NMR ꢁ 35.20 (q, Jˆ2.2 Hz), 42.49,
44.42 (q, Jˆ27.6 Hz), 55.24, 62.28, 114.15, 126.08,
126.12, 126.75 (q, Jˆ279.5 Hz), 130.26, 153.57, 159.70,
169.85. 19F NMR ꢁ 8.44 (d, Jˆ8.9 Hz). IR (neat) ꢂ 3102,
169.13. 19F NMR ꢁ 8.44 (d, Jˆ8.9 Hz). IR (neat) ꢂ 3021,
1
1783, 1711, 758 cm
.
(S)-3-[(S)-4,4,4-Tri¯uoro-3-methylbutanoyl]-4-phenyloxa-
zolidin-2-one (7c). MeLi in Et2O (1.06 M; 1.5 mmol) was
slowly added to a solution of 0.285 g (1.5 mmol) of puri®ed
CuI in 3 ml of Et2O at 308C and stirred for 30 min at that
temperature. To this organocopper solution was added at
788C a suspension of (S)-3-[(E)-4,4,4-tri¯uorobut-2-
enoyl]-4-phenyloxazolidin-2-one 4 (0.143 g, 0.5 mmol) and
MgBr2 (0.276 g, 1.5 mmol) in Et2O (1 ml). After stirring for
2 h at 788C, the similar work-up as above, followed by
puri®cation by silica gel column chromatography or recrys-
tallizationaffordedthedesiredmaterial7din68%yield(>98%
21
de). ‰ꢀŠ
47.648 (c 0.47, CHCl3). 1H NMR ꢁ 1.06 (3H, d,
D
Jˆ6.58 Hz), 2.82±2.90 (1H, m), 3.01 (1H, dd, Jˆ7.99,
16.92 Hz), 3.31 (1H, dd, Jˆ4.23, 16.92 Hz), 4.31 (1H, dd,
Jˆ3.29, 8.46 Hz), 4.73 (1H, t, Jˆ8.46 Hz), 5.44 (1H, dd,
Jˆ3.53, 8.23 Hz), 7.29±7.31 (2H, m), 7.34±7.42 (3H, m).
13C NMR ꢁ 13.19 (q, Jˆ3.0 Hz), 33.99 (q, Jˆ27.7 Hz),
35.99 (q, Jˆ2.5 Hz), 57.69, 70.10, 125.83, 127.74 (q,
Jˆ279.1 Hz), 128.86, 129.20, 129.24, 138.69, 153.57,
169.66. 19F NMR ꢁ 5.14 (d, Jˆ8.2 Hz). IR (KBR) ꢂ 3062,
1
2989, 2938, 2841, 1789, 1711, 1614, 1517, 832, 768, 735,
3035, 2988, 2941, 2924, 1786, 1709, 739, 701 cm
.
(S)-3-[(R)-3-(Tri¯uoromethyl)pent-4-enoyl]-4-phenylox-
1
673, 626 cm
(S)-3-[(R)-4,4,4-Tri¯uoro-3-(4-methoxyphenyl)butanoyl]-
.
22
D
azolidin-2-one (7d). Yield 80%. de>98%. ‰ꢀŠ
69.728 (c
4-phenyl-oxazolidin-2-one (7a). Yield 94%. de 62%.
0.99, CHCl3). M.p. 93±948C. 1H NMR ꢁ 3.25 (1H, dd,
Jˆ5.09, 16.65 Hz), 3.38 (1H, dd, Jˆ7.69, 16.77 Hz), 3.40±
3.60 (1H, m), 4.31 (1H, dd, Jˆ3.81, 8.95 Hz), 4.72 (1H, t,
Jˆ8.83 Hz), 5.13 (1H, qd, Jˆ0.76, 9.45 Hz), 5.18±5.21
(1H, m), 5.44 (1H, dd, Jˆ4.03, 8.80 Hz), 5.56±5.77 (1H,
m), 7.24±7.40 (5H, m). 13C NMR ꢁ 34.05 (q, Jˆ2.4 Hz),
43.37 (q, Jˆ27.8 Hz), 57.71, 70.70, 121.40, 125.88, 126.27
(q, Jˆ279.4 Hz), 128.83, 129.12, 129.96 (q, Jˆ2.6 Hz),
26
D
1
‰ꢀŠ
33.798 (c 0.55, CHCl3). M.p. 152±1558C. H NMR
ꢁ3.32±3.47(1H,m),3.80(3H,s),3.75±4.01(2H,m),4.17(1H,
dd, Jˆ4.04, 8.89 Hz), 4.65 (1H, t, Jˆ8.80 Hz), 5.37 (1H, dd,
Jˆ4.08, 8.07 Hz), 6.79±6.99 (4H, m), 7.12±7.24 (5H, m),
7.42±7.46 (1H, m). 13C NMR ꢁ 34.89 (q, Jˆ2.4 Hz), 44.80
(q, Jˆ27.9 Hz), 55.20, 57.57, 69.96, 114.01, 125.24, 126.44
(q, Jˆ282.5 Hz), 127.69, 128.41, 129.01, 130.21, 138.09,
153.52, 159.54, 169.20. 19F NMR ꢁ 8.13 (d, Jˆ7.6 Hz). IR
138.39, 153.56, 169.02. 19F NMR ꢁ 7.54 (d, Jˆ7.6 Hz).
1
.
1
(neat) ꢂ 3054, 1783, 1265, 739, 704 cm
(S)-3-[(R)-4,4,4-Tri¯uoro-3-(4-methoxyphenyl)butanoyl]-
IR (KBr) ꢂ 3056, 2987, 1784, 1711, 1266, 739, 704 cm
.
(S)-3-[(S)-3-(Tri¯uoromethyl)heptanoy]-4-phenyloxazoli-
din-2-one (7g). To a solution of the organocopper reagent
prepared from n-BuLi (0.63 ml, 1.0 mmol) and 0.190 g
(1.0 mmol) of CuI in Et2O (3 ml) at 308C was added a
suspension of 4 (0.143 g, 0.5 mmol) and LiBr (0.276 g,
1.5 mmol) in Et2O (1 ml) at 788C. After stirring for 2 h at
that temperature and usual work-up, puri®cation by silica gel
column chromatography furnished 7g in 65% yield (de 87%).
4-phenylmethyl)-oxazolidin-2-one (8a). Yield quant. de 50%.
23
1
‰ꢀŠ ‡58.288 (c 0.52, CHCl3). H NMR ꢁ 2.61 (1H, dd,
D
Jˆ9.03, 13.67 Hz), 2.96 (1H, dd, Jˆ3.17, 13.67 Hz), 3.41
(1H,dd,Jˆ4.40,17.58 Hz),3.80(3H,s),3.85(1H,dd,Jˆ9.77,
17.58 Hz), 4.08 (1H, dquint, Jˆ4.39, 9.52 Hz), 4.14 (1H, dd,
Jˆ2.93, 9.04 Hz), 4.21 (1H, t, Jˆ8.55 Hz), 4.63 (1H, m),
6.85±6.95 (4H, m), 7.24±7.36 (5H, m). 13C NMR ꢁ 33.40

96
T. Yamazaki et al. / Journal of Fluorine Chemistry 97 (1999) 91±96
22
D
Biomedical Frontiers of Fluorine Chemistry, ACS, Washington,
‰ꢀŠ
22.228C (c 2.34, CHCl3). 1H NMR ꢁ 0.75±0.85 (3H,
DC, 1996, p. 105.
m),1.12±1.42(5H,m),1.52±1.71(1H,m),2.71±2.95(1H,m),
3.02 (1H, dd, Jˆ6.19, 18.17 Hz), 3.29 (1H, dd, Jˆ5.84,
18.11 Hz), 4.31 (1H, dd, Jˆ3.75, 8.96 Hz), 4.72 (1H, t,
Jˆ8.82 Hz), 5.44 (1H, dd, Jˆ3.76, 8.70 Hz), 7.27±7.40
(5H, m). 13C NMR ꢁ 13.70, 22.51, 28.14 (q, Jˆ2.3 Hz),
28.58, 34.42 (q, Jˆ2.8 Hz), 38.43 (q, Jˆ26.2 Hz), 57.81,
70.13, 125.96, 127.95 (q, Jˆ279.9 Hz), 128.87, 129.23,
138.79, 153.66, 170.00. 19F NMR ꢁ 7.44 (d, Jˆ9.2 Hz). IR
[8] C.-L.J. Wang, Org. React. 34 (1985) 319.
[9] M. Hudlicky, Org. React. 35 (1988) 513.
[10] K. Kanie, K. Mizuno, M. Kuroboshi, T. Hiyama, Bull. Chem. Soc.
Jpn. 97 (1998) 1973.
[11] G.K. Surya Prakash, A.K. Yudin, Chem. Rev. 97 (1997) 757.
[12] T. Umemoto, Chem. Rev. 97 (1997) 1757.
[13] T. Taguchi, G. Tomizawa, A. Kawara, M. Nakajima, Y. Kobayashi, J.
Fluorine Chem. 40 (1998) 171.
[14] H. Tsuge, K. Takumi, T. Nagai, T. Okano, S. Eguchi, H. Kimoto,
Tetrahedron 53 (1997) 823.
(KBr) ꢂ 3065, 3036, 2958, 2871, 1790, 1703, 759, 712,
1
.
[15] I. Ojima, F.A. Jameison, Bioorg. Med. Chem. Lett. 1 (1991) 581.
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Jpn. 67 (1994) 3021.
697 cm
(S)-3-(4,4-Di¯uorobut-3-enoyl)-4-phenyloxazolidin-2-one
22
D
1
(9). ‰ꢀŠ
35.718 (c 0.94, CHCl3). H NMR ꢁ 3.63 (1H,
tdd, Jˆ1.83, 7.34, 19.04 Hz), 3.72 (1H, tdd, Jˆ1.44, 7.45,
19.17 Hz), 4.33 (1H, ddd, Jˆ2.20, 3.67, 9.04 Hz), 4.43 (1H,
dtd, Jˆ1.71, 7.39, 25.03 Hz), 4.72 (1H, dt, Jˆ1.87,
8.85 Hz), 5.42 (1H, dd, Jˆ4.08, 8.42 Hz), 7.26±7.40 (5H,
m). 13C NMR ꢁ 29.85 (d, Jˆ5.6 Hz), 57.56, 71.22 (dd,
Jˆ19.2, 29.2 Hz), 125.86, 128.74, 129.10, 138.60, 156.61
(dd, Jˆ286.5, 289.2 Hz), 169.20 (dd, Jˆ2.0, 3.5 Hz),
169.46. 19F NMR ꢁ 10.39 (1F, dd, Jˆ24.5, 41.7 Hz),
[18] S. Iwata, Y. Ishiguro, M. Utsugi, H. Yamanaka, Bull. Chem. Soc.
Jpn. 66 (1993) 2432.
[19] Y.-C. Shen, M. Qi, J. Chem. Res. (S) (1996) 328.
[20] M. Sato, F. Uehara, H. Kamaya, M. Murakami, C. Kaneko, T.
Furuya, H. Kurihara, Chem. Commun. (1996) 1063.
[21] O. Klenz, R. Evers, R. Miethchen, M. Michalik, J. Fluorine Chem.
81 (1997) 205.
[22] M. Gautschi, D. Seebach, Angew. Chem., Int. Ed. Engl. 31 (1992)
1083.
[23] T. Yamazaki, K. Takita, N. Ishikawa, Nippon Kagakukai Shi (1985)
2131.
7.55 (1F, d, Jˆ41.3 Hz). IR (KBr) ꢂ 3056, 1783, 1755,
1
1712, 1266, 738, 705 cm
Crystallographic data. Diffraction data were collected on
.
[24] T. Yamazaki, N. Ishikawa, H. Iwatsubo, T. Kitazume, J. Chem. Soc.,
Chem. Commun. (1987) 1340.
a Rigaku AFC5R diffractometer at 298 K with graphite
Ê
[25] T. Yamazaki, S. Hiraoka, T. Kitazume, J. Org. Chem. 59 (1994) 5100.
[26] N. Shinohara, J. Haga, T. Yamazaki, T. Kitazume, S. Nakamura, J.
Org. Chem. 60 (1995) 4363.
monochromated Mo Kꢀ radiation (ꢃˆ0.71069 A). The
structure was solved by direct methods with MULTAN88
and expanded using Fourier techniques with DIRDIF94.
Non-hydrogen atoms were re®ned anisotropically and some
hydrogen atoms were re®ned isotropically, the rest were
included in ®xed positions.
[27] P.F. Bevilacqua, D.D. Keith, J.L. Roberts, J. Org. Chem. 49 (1984)
1430.
[28] D. Gestmann, A.J. Laurent, E.G. Laurent, J. Fluorine Chem. 80
(1996) 27.
Â
[29] A. Bensadat, C. Felix, A. Laurent, E. Laurent, R. Faure, T. Thomas,
Bull. Soc. Chim. Fr. 113 (1996) 509.
C21H20F3NO3 (recrystallized from a mixture of n-hexane
and AcOEt), orthorhombic, space group P212121 (no. 19),
[30] L. Antolini, A. Forni, I. Moretti, F. Prati, E. Laurent, D. Gestmann,
Tetrahedron: Asym 7 (1996) 3309.
Ê
Ê 3
aˆ13.115(3), bˆ24.305(3), cˆ6.388(3) A, Vˆ2036.3(8) A ,
Zˆ4, Dcalcˆ1.329 g cm 3, ꢄˆ1.10 cm 1, F0 0 0ˆ848.00,
crystal size 0.60Â0.50Â0.70 mm3, 5308 collected re¯ec-
tions, 2716 unique re¯ections, goodness of ®t 2.30, re®ne-
ment converged with Rˆ0.044 and Rwˆ0.060.
[31] D.A. Evans, M.T. Bilodeau, T.C. Somers, J. Clardy, D. Cherry, Y.
Kato, J. Org. Chem. 56 (1991) 5750.
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[34] D.A. Evans, Aldrichim. Acta 15 (1982) 23.
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Kato, J. Org. Chem. 56 (1991) 5750.
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