Regioselective, stereospecific, and chemoselective fluorination of epoxy alcohols: Development of fluorinating hybrid reagents, associated with Lewis acid metal fluoride/ammonium hydrogen fluoride

Article abstract of DOI:10.1016/S0022-328X(02)01888-0

A new type of fluorinating reagent of Lewis acid metal fluoride/ammonium hydrogen fluoride is developed for regio-, stereo-, and chemoselective ring opening fluorination of epoxy alcohols.

Full text of DOI:10.1016/S0022-328X(02)01888-0

Journal of Organometallic Chemistry 662 (2002) 77Á82
/
www.elsevier.com/locate/jorganchem
Regioselective, stereospecific, and chemoselective fluorination of
epoxy alcohols: development of fluorinating hybrid reagents,
associated with Lewis acid metal fluoride/ammonium hydrogen
fluoride
Koichi Mikami *, Shiho Ohba, Hirofumi Ohmura
Department of Applied Chemistry, Tokyo Institute of Technology, Ookayama, Meguro-ku, Tokyo 152-8552, Japan
Received 28 March 2002; accepted 5 September 2002
Abstract
A new type of fluorinating reagent of Lewis acid metal fluoride/ammonium hydrogen fluoride is developed for regio-, stereo-, and
chemoselective ring opening fluorination of epoxy alcohols.
#
2002 Elsevier Science B.V. All rights reserved.
Keywords: Regioselective fluorination; Epoxy alcohols; Fluorinating hybrid reagents
1
. Introduction
can also be carried out with tetrabutylammonium
ꢀ
ꢁ
3
dihydrogen trifluoride (Bu N H F ; TBAH F ) [6,7].
4
2
2 3
ꢁ
Several methods have recently been developed to give
The coproduced reagent TBAHF2 is reported to be
readily converted back to TBAH F by KHF [7]. The
chiral organo-fluorine compounds [1], as recent exam-
ples of enantioselective electrophilic fluorination. One of
the simplest methods for asymmetric introduction of a
fluorine substituent into a molecule involves the
2
3
2
order of nucleophilicity and selectivity of a fluoride ion
is reported: nucleophilicity [8]: TBAFꢀTBAHF ꢀ
TBAPh SnF , TBAPh SiF ; selectivity: TBAHF Â
/
/
2
/
3
2
3
2
2
SharplessÁ
/
Katsuki asymmetric epoxidation [2] followed
TBAPh SiF ꢀ
/
anhydrous TBAF. However, even by
using TBAH F , ring opening fluorination of epoxy
3
2
by ring opening fluorination leading to enantio-enriched
fluorohydrine. Epoxides undergo a ring-opening fluor-
ination by HF/amine complex such as HF/pyridine [3] to
react, however, also with olefin [4]. Potassium hydrogen
2
3
alcohols generally provides the regioisomeric mixture
with 3-fluorinated 1,2-diols as the major one (Eq. (1))
[6,9]. Thus, the high regio- and stereocontrol in ring-
opening fluorination of epoxide to give 2-fluorinated
1,3-diols has remained as a challenging problem. Herein
reported are fluorinating hybrid reagents of Lewis acid
fluoride or potassium difluoride, KHF also serve as
2
fluorinating reagents and react with epoxides to give
fluorohydrins [5]. Ring-opening fluorination of epoxides
ð1Þ
*
E-mail address: kmikami@o.cc.titech.ac.jp (K. Mikami).
Corresponding author. Tel.: ꢀ
/
81-3-5734-2142; fax: ꢀ81-3-5734-2776
/
0022-328X/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 3 2 8 X ( 0 2 ) 0 1 8 8 8 - 0

78
K. Mikami et al. / Journal of Organometallic Chemistry 662 (2002) 77Á82
/
Table 1
Ring opening fluorination with Lewis acidic metal salts and ammonium hydrogen fluoride
a
a
Entry
MF
n
Reagent
HF/Py
Temperature (8C)
Time (h)
2Fꢀ3F
2F:3F
1
2
3
Á/
Á/
0
1
20
24
Complex mixture
60%
No reaction
Á/
39:61
H
H
2
F
F
3
NBu
NBu
4
4
140
r.t.
ScF
3
2
3
Á/
b
4
TiF
4
H
2
F
3
NBu
4
r.t.
8
86%
66:34
5
6
7
FeF
CuF
3
H
H
H
2
F
2
F
2
F
3
NBu
3
NBu
3
NBu
4
4
4
r.t.
r.t.
r.t.
24
24
72
No reaction
No reaction
20%
Á
Á/
/
2
c
SnF
2
65:35
a
19
Yield and ratio were determined by F-NMR.
%
Isolated yield.
b
c
2 2
CH Cl was used.
metal fluoride/ammonium hydrogen fluoride for regio-,
stereo-, and chemoselective ring opening fluorination of
epoxy alcohols.
mediated the fluorination reaction under mild condi-
tions to give fluorohydrins in high yields. The regios-
electivity depends on the combination of metals and
solvents employed. Therefore, the C-2- or C-3-fluori-
nated products can be obtained selectively. The highest
2
. Results and discussion
C-2-regioselectivity was obtained when HfF was used
4
with TBA×
/
H F (4) in THF (entry 8).
2 3
In the presence of a variety of metal fluorides, chemo-
Then we examined the characteristic feature of Group
4 transition metal fluorides by the ring opening fluor-
ination of styrene oxide. When metal fluorides activate
epoxides as Lewis acids, the reaction will proceed via
stable carbenium ion intermediate to give the secondary
fluoride product. On the other hand, when metal
fluorides/ammonium fluoride hybride reagents are nu-
cleophilic rather than Lewis acidic, the fluoride will
attack the less hindered side to give the primary
fluorinated product (Scheme 1).
and regioselectivities in ring opening fluorination of
epoxyalcohol (1) as a highly functionalized substrate
were examined. The results with the combined use of
Lewis acidic metal salts and ammonium hydrogen
fluoride are shown in Table 1. Titanium tetrafluoride
assisted the fluorination reaction under mild conditions
to give fluorohydrins in high yields. The reaction in
chlorobenzene was completed within 8 h at room
temperature and the expected fluorohydrins (2, 3) were
obtained in 86% yield. C-2-fluorinated product (2) was
obtained as the major product (entry 4). The structures
of the fluorohydrins (2, 3) were determined to show the
The results of the ring opening fluorination of styrene
oxide (5) are shown in Table 3. In the reaction of 5 with
4 without metal fluoride, primary fluorinated product
(7) was obtained predominantly (entry 1). While in the
presence of metal fluorides, only secondary fluorinated
product (6) was obtained and the aldehyde (8) was also
obtained as a by-product (entry 2). The formation of the
aldehyde (8) suggests that the reaction proceeds via
benzylic carbenium ion intermediate and hydride shift
takes place to give aldehyde 8 (Scheme 2). Therefore, the
metal fluorides are likely to activate the epoxides as
Lewis acid metal complexes.
stereospecific S 2 inversion process by the decoupling of
N
1
the allylic proton in H-NMR and also confirmed by CÁ
/
1
F coupling constant of C-NMR (see Section 3).
3
Thus, we focused our attention on the regioselectivity
of fluorination by changing Group 4 transition metal
fluorides (Table 2). Group 4 transition metal fluorides
Table 2
Ring opening fluorination using Group 4 transition metals
a
a
In the reaction of 2,3-epoxyhexanol (9) with 4 and
metal fluorides, C-3-fluorinated product was obtained
predominantly (Table 4). The highest C-3-regioselectiv-
Entry MF
n
Solvent
Time (h)
2Fꢀ3F (%)
2F:3F
1
2
3
4
5
6
7
8
TiF
4
3
CH
THF
CH CI
THF
CH Cl
THF
CH Cl
THF
2
Cl
2
8
24
19
48
8
58
67
78
77
65
67
83
81
42:58
59:41
60:40
63:37
60:40
74:26
63:37
74:26
ity (89% selective) was obtained when TiF was used
4
TiF
2
2
with 4 in CH Cl (Entry 2).
2
2
ZrF
4
2
2
2
Next, the effect of steric bulkiness around the epoxide
ring was examined on the regioselectivity of fluorination
of 12 (Table 5). The C-3-regioselectivity was decreased
as compared with 9. Interestingly, in comparison with 1,
C-2-regioselectivity of 12 was lower than that of 1. It
8
HIF
4
2
4
4
a
19
Yield and ratio were determined by F-NMR.
%

K. Mikami et al. / Journal of Organometallic Chemistry 662 (2002) 77Á
/82
79
Scheme 1.
Table 3
Ring opening fluorination of styrene oxide
a
a
b
Entry
MF
4
Solvent
Temperature (8C)
Time (h)
6ꢀ7 (%)
6:7
8
(%)
1
2
3
Á
TIF
/
PhCl
THF
THF
140
r.t.
r.t.
5
1
3
84
46
40
35:65
100:0
100:0
Á
10
/
4
HfF
4
15
a
19
Yield and ratio were determined by F-NMR.
1
Yield was determined by H-NMR.
%
b
%
Scheme 2.
suggests that olefin functionality has significant effect in
increasing the C-2-regioselectivity, presumably because
of the electron withdrawing effect.
(Table 6). The regioselectivity was almost the same as
9. It is clear that the olefin functionality is necessary to
increase the C-2 regioselectivity.
Then, the effect of the olefin was examined by
fluorination of 15 obtained via hydrogenation of 1
The plausible mechanism is shown in Scheme 3. The
regioselectivity largely depends on the ionic radii of
Table 4
Ring opening fluorination of 2,3-epoxyhexanol
a
a
Entry
MF
n
Solvent
Temperature (8C)
Time (h)
2Fꢀ3F
2F:3F
b
1
2
3
Á
/
PhCl
CH
THF
140
r.t.
r.t.
18
4
90
92
74
21:79
11:89
39:61
TiF
4
2 2
Cl
HfF
4
4
a
19
Yield and ratio were determined by F-NMR.
%
b
Two equivalents of H NBu was used.
3
2
F
4

80
K. Mikami et al. / Journal of Organometallic Chemistry 662 (2002) 77Á82
/
Table 5
Ring opening fluorination of 2,3-epoxy-4-methylpentanol
a
a
Entry
MF
n
Solvent
Temperature (8C)
Time (h)
2Fꢀ3F
2F:3F
b
1
2
3
Á
/
PhCl
CH
THF
140
r.t.
r.t.
24
4
69
74
76
33:67
20:80
63:37
TiF
4
2 2
Cl
HfF
4
24
a
19
Yield and ratio were determined by F-NMR.
%
b
Two equivalents of H NBu was used.
3
2
F
4
Table 6
Ring opening fluorination of 2,3-epoxy-5-methylhexanol
a
a
Entry
MF
n
Solvent
Temperature (8C)
Time (h)
2Fꢀ3F
2F:3F
b
1
Á
TiF
/
PhCl
CH
THF
140
r.t.
r.t.
24
6
57
56
71
13:87
14:86
39:61
2
3
4
2 2
Cl
HfF
4
6
a
19
Yield and ratio were determined by F-NMR.
%
b
Two equivalents of H NBu was used.
3
2
F
4
Scheme 3.
Group 4 transition metals. The smallest Ti leads to the
small five-membered dioxametallacycle via C-3-fluori-
nation. By contrast, the largest Hf affords the large six-
membered ring with a coordinating and bulky solvent
2a- and 2b-fluorinated A-ring analogs of 19-nor-
1a,25(OH) D which are useful for the analysis of the
VDR-binding conformation of the A-rings on the basis
2
3
1
9
of the F-NMR analysis [11].
(
THF) via C-2-fluorination.
In summary, we have thus developed the fluorinating
hybrid reagents associated with Lewis acid metal
fluorides/ammonium hydrogen fluoride for regioselec-
tive, stereospecific, and chemoselective ring opening
fluorination of epoxy alcohols. The highly regio-,
stereo-, and chemoselective ring opening fluorination
of epoxy alcohol 1 can be employed in the synthesis of
3. Experimental
3.1. General
1
13
H-NMR and C-NMR spectra were measured on a
Varian GEMINI 300 (300 MHz) and a Varian GEMINI

K. Mikami et al. / Journal of Organometallic Chemistry 662 (2002) 77Á
/82
81
1
00 (400 MHz) spectrometers, F-NMR spectra were
9
3
2
1
4
measured on a Varian GEMINI 400 (400 MHz)
Jꢂ
/
4.9 Hz), 72.9 (d, Jꢂ
/
23.0 Hz), 92.1 (d, Jꢂ
/172.3
Hz), 113.5, 141.2.
1
spectrometer. Chemical shifts of H-NMR were ex-
pressed in parts per million downfield from Me Si as an
4
3.2.3. 2-Fluoro-2-phenylethanol (6)
1
9
internal standard (dꢂ0) in CDCl . Chemical shifts of
/
3
F-NMR (376 MHz, CDCl ) d ꢁ
/
186.0 (ddd, Jꢂ
/
3
1
3
1
49.3, 29.7, 20.7 Hz, 1F). H-NMR (300 MHz, CDCl )
C-NMR were expressed in parts per million in CDCl3
3
as an internal standard (dꢂ
/
77.1). Chemical shifts of
F-NMR were expressed in parts per million downfield
from BTF as an internal standard (dꢂ 63.24) in
CDCl3.
d 3.67Á
(
4
/
3.78 (ddd, Jꢂ
ddd, Jꢂ19.2, 12.4, 8.0 Hz, 1H), 5.41Á
9.32, 8.0, 3.2 Hz, 1H), 7.26Á7.37 (m, 5H).
/
30.8, 12.4, 3.2 Hz, 1H), 3.80Á3.89
/
1
9
/
/
5.56 (ddd, Jꢂ
/
/
ꢁ
/
/
3
.2.4. 2-Fluoro-1-phenylethanol (7)
1
9
3.2. General procedure for fluorohydrin synthesis:
(2R,3S)-2-fluoro-5-methyl-5-hexene-1,3-diol (2) and
(2R,3S)-3-fluoro-5-methyl-5-hexene-1,2-diol (3)
F-NMR (376 MHz, CDCl ) d ꢁ
/
221.4 (td, Jꢂ
/
48.1,
3
1
15.0 Hz, 1F). H-NMR (300 MHz, CDCl ) d 4.30Á
/
4.47
4.50 (ddd, Jꢂ
4.95 (ddd, Jꢂ14.0, 7.6, 4.0
7.32 (m, 5H).
3
(ddd, Jꢂ
8.4, 9.6, 4.0 Hz, 1H), 4.89Á
Hz, 1H), 7.26Á
/
48.4, 9.6, 7.6 Hz, 1H), 4.35Á
/
/
4
/
/
A 10-ml test tube with Ar inlet was charged with
/
hafnium (IV) tetrafluoride (133 mg, 0.52 mmol) and
THF (2.0 ml) at 0 8C. To the suspension was added
tetrabutylammonium dihydrogentrifluoride (H F -
3
.2.5. 2-Fluoro-hexane-1,3-diol (10)
1
9
2
3
F-NMR (376 MHz, CDCl ) d ꢁ
/
195.9 (dtd, Jꢂ
/
3
1
47.4, 25.8, 11.0 Hz, 1F). H-NMR (400 MHz, CDCl )
NBu ) (4) [10] (166 mg, 0.55 mmol) in THF (0.5 ml)
4
3
and stirred for 10 min at that temperature. (2R,3S)-5-
Methyl-2,3-epoxyhex-5-en-1-ol (1) (60 mg, 0.47 mmol)
was added dropwise and, after 10 min of stirring, the
reaction mixture was warmed up to room temperature.
After stirring for 8 h at that temperature, the reaction
mixture was quenched with a saturated aqueous solu-
tion of sodium hydrogencarbonate. The aqueous layer
was extracted three times with ether, and the combined
organic layers were washed with brine and dried over
anhydrous magnesium sulfate. After evaporation under
reduced pressure, the resultant residue was purified by
silica-gel chromatography to give (2R,3S)-2-fluoro-5-
methyl-5-hexene-1,3-diol (2) and (2R,3S)-3-fluoro-5-
methyl-5-hexene-1,2-diol (3). The regioselectivity and
d 0.94 (t, Jꢂ
(
/
7.2 Hz, 3H), 1.39Á
m, 2H), 3.35 (brs, 2H), 3.80Á3.93 (m, 3H), 4.26Á
dtd, Jꢂ
/
1.51 (m, 2H), 1.52Á
/
1.63
/
/
4.41
1
3
(
/47.2, 4.8, 3.2 Hz, 1H). C-NMR (101 MHz,
3
2
CDCl ) d 13.9, 18.7, 34.8 (d, Jꢂ
/
3.8 Hz), 61.7 (d, Jꢂ
/
3
2
1
21.4 Hz), 70.5 (d, Jꢂ
/
23.7 Hz), 95.3 (d, Jꢂ173.8 Hz).
/
3
.2.6. 3-Fluoro-hexane-1,2-diol (11)
19
F-NMR (376 MHz, CDCl ) d ꢁ
/
193.6 (dddd, Jꢂ
8.9, 34.2, 20.3, 12.4 Hz, 1F). H-NMR (400 MHz,
7.2 Hz, 3H), 1.35Á1.44 (m, 1H),
1.59 (m, 2H), 1.61Á1.69 (m, 1H), 3.46 (brs, 2H),
3.76 (m, 3H), 4.36Á4.52 (dtd, Jꢂ48.0, 6.8, 5.2 Hz,
H). C-NMR (101 MHz, CDCl ) d 13.8, 18.4 (d, Jꢂ
/
3
1
4
CDCl ) d 0.94 (t, Jꢂ
/
/
3
1
3
1
3
.50Á
/
/
.62Á
/
/
/
13
3
/
3
3
3
.0 Hz), 33.2 (d, Jꢂ
/
20.6 Hz), 62.7 (d, Jꢂ5.4 Hz), 73.1
/
1
9
yield were determined by F-NMR by using BTF as an
internal standard; 2:3ꢂ74:26 (74% yield).
2
1
(d, Jꢂ
/
23.7 Hz), 93.7 (d, Jꢂ
/
170.8 Hz).
/
3
.2.7. 2-Fluoro-4-methyl-pentane-1,3-diol (13)
1
9
3
.2.1. (2R,3S)-2-Fluoro-5-methyl-5-hexene-1,3-diol (2)
1
F-NMR (376 MHz, CDCl ) d ꢁ
/
197.2 (dtd, Jꢂ
/
3
9
1
47.0, 26.3, 7.9 Hz, 1F). H-NMR (400 MHz, CDCl )
F-NMR (376 MHz, CDCl ) d ꢁ
/
197.7 (dtd, Jꢂ
/
3
3
1
6.6, 25.2, 9.0 Hz, 1F). H-NMR (300 MHz, CDCl )
4
3
d 0.96 (d, Jꢂ
/
6.8 Hz, 6H), 1.88 (q, Jꢂ
/
6.8 Hz, 1H), 3.01
d 1.78 (s, 3H), 2.18 (dd, Jꢂ
Jꢂ14.1 Hz, 1H), 2.56 (bs, 2H), 3.93 (dd, Jꢂ
Hz, 2H), 4.00 (dddd, Jꢂ10.2, 9.3, 6.3, 3.3 Hz, 1H),
47.1, 6.3, 4.2 Hz, 1H), 4.84 (s, 1H),
.92 (s, 1H). C-NMR (75 MHz, CDCl ) d 22.3, 41.7
/
14.1, 10.2 Hz, 1H), 2.41 (bd,
(bs, 1H), 3.23 (bs, 1H), 3.66Á
/
3.70 (m, 1H), 3.88 (d, Jꢂ
/
/
/
25.2, 4.2
3
Jꢂ
.2 Hz, 1H), 3.94 (d, Jꢂ
/
2.4 Hz, 1H), 4.40Á
/4.55 (ddt,
1
47.2, 6.8, 3.6 Hz, 1H). C-NMR (101 MHz, CDCl )
3
/
/
3
3
2
4
4
.26Á
/
4.46 (ddd, Jꢂ
/
d 18.7, 19.1, 29.7 (d, Jꢂ
/
3.8 Hz), 62.2 (d, Jꢂ22.2 Hz),
/
1
3
2
1
3
74.9 (d, Jꢂ
/
22.9 Hz), 93.2 (d, Jꢂ171.5 Hz).
/
3
2
2
(
d, Jꢂ
/
3.7 Hz), 62.2 (d, Jꢂ
/
20.6 Hz), 68.0 (d, Jꢂ
/25.4
1
Hz), 95.0 (d, Jꢂ
/
171.1 Hz), 114.4, 141.5.
3
.2.8. 3-Fluoro-4-methyl-pentane-1,2-diol (14)
1
9
F-NMR (376 MHz, CDCl ) d ꢁ
/
204.3 (dddd, Jꢂ
/
3
1
49.3, 26.3, 13.9 Hz, 1F). H-NMR (400 MHz, CDCl ) d
3
.2.2. (2R,3S)-3-Fluoro-5-methyl-5-hexene-1,2-diol (3)
3
1
9
F-NMR (376 MHz, CDCl ) d ꢁ
/
191.0 (dddd, Jꢂ
8.3, 37.6, 19.2, 10.2 Hz, 1F). H-NMR (300 MHz,
2.48 (m, 2H), 2.52 (bs, 2H),
4.74 (dddd, Jꢂ48.3, 8.7, 4.8,
/
0.97 (d, Jꢂ
2.05 (dqd, Jꢂ
(bs, 1H), 3.66Á
3.79 (d, Jꢂ10.4 Hz, 1H), 4.14Á
/
6.8 Hz, 3H), 0.99 (d, Jꢂ
25.6, 6.8, 2.0 Hz, 1H), 3.23 (bs, 1H), 3.53
3.70 (m, 1H), 3.76 (d, Jꢂ10.4 Hz, 1H),
4.29 (ddd, Jꢂ48.0, 6.0,
5.2 Hz, 1H). C-NMR (101 MHz, CDCl ) d 16.1 (d,
/
6.8 Hz, 3H), 1.94Á
/
3
1
5
/
CDCl ) d 1.79 (s, 3H), 2.36Á
3
3
/
/
/
3
.71Á
/
3.80 (m, 3H), 4.52Á
/
/
/
/
/
1
3
13
.0 Hz, 1H), 4.84 (s, 1H), 4.87 (s, 1H). C-NMR (75
2
3
3
3
2
MHz, CDCl ) d 22.8, 39.6 (d, Jꢂ
/20.6 Hz), 62.7 (d,
Jꢂ
/
5.4 Hz), 18.9 (d, Jꢂ
/
5.4 Hz), 28.8 (d, Jꢂ20.0
/
3

82
K. Mikami et al. / Journal of Organometallic Chemistry 662 (2002) 77Á82
/
3
2
Hz), 63.0 (d, Jꢂ
/
4.5 Hz), 70.8 (d, Jꢂ
/25.3 Hz), 94.5 (d,
References
1
Jꢂ173.9 Hz).
/
[
1] T. Hiyama, K. Kanie, T. Kusumoto, Y. Morizawa, M. Shimizu,
Organofluorine Compounds: Chemistry and Applications,
Springer, Berlin, 2000.
3
.2.9. (2R,3S)-2-Fluoro-5-methyl-hexane-1,3-diol (16)
1
[
2] (a) T. Katsuki, V.S. Martin, Org. React. 48 (1996) 1;
(b) R.A. Johnson, K.B. Sharpless, in: B.M. Trost, I. Fleming
(Eds.), Comprehensive Organic Synthesis, vol. 7, Pergamon,
London, 1991, p. 389;
9
F-NMR (376 MHz, CDCl ) d ꢁ
/
195.2 (bddd, Jꢂ
/
3
1
6.6, 26.3, 9.0 Hz, 1F). H-NMR (400 MHz, CDCl ) d
4
0
1
5
4
3
.90 (d, Jꢂ
H), 3.87 (dd, Jꢂ
.2 Hz, 1H), 3.92Á
7.2, 5.2, 3.2 Hz, 1H). C-NMR (101 MHz, CDCl ) d
/
6.8 Hz, 6H), 1.77Á
14.8, 5.2 Hz, 1H), 3.93 (dd, Jꢂ
4.00 (m, 2H), 4.25Á4.28 (dtd, Jꢂ
/
1.86 (m, 3H), 3.54 (bs,
(
(
c) R.M. Hanson, K.B. Sharpless, J. Org. Chem. 51 (1986) 1922;
d) K.B. Sharpless, S.S. Woodard, M.G. Finn, Pure Appl. Chem.
/
/14.8,
/
/
/
5
5 (1983) 1823.
1
3
3
[3] (a) R. Skupin, G. Haufe, J. Fluorine Chem. 92 (1998) 157;
(b) A. Sattler, G. Haufe, J. Fluorine Chem. 69 (1994) 185;
(c) J. Umezawa, O. Takahashi, K. Furuhashi, H. Nohira,
Tetrahedron: Asymmetry 4 (1993) 2053;
2
2
1.5, 23.6, 24.4, 41.6, 61.7 (d, Jꢂ
/
22.1 Hz), 69.0 (d,
2
1
Jꢂ
/
23.0 Hz), 95.7 (d, Jꢂ
/
173.1 Hz).
(
d) H. Suga, T. Hamatani, M. Schlosser, Tetrahedron 46 (1990)
247;
e) M. Muehlbacher, C.D. Poulter, J. Org. Chem. 53 (1988) 1026;
4
3
(
.2.10. (2R,3S)-3-Fluoro-5-methyl-hexane-1,2-diol
17)
(
(f) G.A. Olah, D. Meidar, Israel J. Chem. 17 (1978) 148.
[4] G.A. Olah, J.T. Welch, Y.D. Vankar, M. Nojima, I. Kerekes, J.A.
Olah, J. Org. Chem. 44 (1979) 3872.
1
9
F-NMR (376 MHz, CDCl ) d ꢁ
/
192.9 (bddd, Jꢂ
/
3
1
7.0, 28.2, 14.7 Hz, 1F). H-NMR (400 MHz, CDCl ) d
4
0
1
3
[5] (a) M. Tamura, T. Shibakami, Arimura, S. Kurosawa, A. Sekiya,
J. Fluorine Chem. 70 (1995) 1;
.93, (d, Jꢂ
.38 (ddd, Jꢂ
14.4, 9.2, 2.4 Hz, 1H), 1.57Á
H), 3.63Á3.76 (m, 4H), 4.45Á4.62 (dddd, Jꢂ
.2, 2.4 Hz, 1H). C-NMR (101 MHz, CDCl ) d 21.7,
/
6.8 Hz, 3H), 0.95 (d, Jꢂ
14.4, 9.2, 2.4 Hz, 1H), 1.42Á
1.68 (m, 1H), 3.47 (bs,
48.8, 10.4,
/
6.8 Hz, 3H), 1.32Á
/
/
/1.49 (ddd,
(
b) J. Ichihara, T. Hanafusa, J. Chem. Soc. Chem. Commun.
(1989) 1848.
[6] M.W. Hager, D.C. Liotta, Tetrahedron Lett. 33 (1992) 7083.
Jꢂ
/
/
1
5
2
7
/
/
/
1
3
[7] (a) D. Landini, D. Albanese, M. Penso, Tetrahedron 48 (1992)
3
2
3
4163;
3.4, 24.5, 40.0 (d, Jꢂ
/
19.9 Hz), 62.6 (d, Jꢂ6.1 Hz),
23.0 Hz), 92.5 (d, Jꢂ170.1 Hz).
/
(
b) D. Landini, M. Penso, Tetrahedron Lett. 31 (1990) 7209.
8] D. Landini, A.M. Maia, A. Rampoldi, J. Org. Chem. 54 (1989)
28.
9] Also see the use of Ti(OPr )
Kameoka, M. Sawaguchi, T. Fukuhara, N. Yoneda, Tetrahedron
5 (1999) 4947.
10] D. Landini, H. Molinari, M. Penso, A. Rampoldi, Synthesis
1988) 953.
2
1
3.5 (d, Jꢂ
/
/
[
[
3
i
2 2
F : S. Hara, T. Hoshio, M.
5
Acknowledgements
[
[
(
We are grateful to Professor Masahiro Terada of
Tohoku University for his useful discussion.
11] K. Mikami, S. Ohba, H. Ohmura, N. Kubodera, K. Nakagawa,
T. Okano, Chirality 13 (2001) 366.