Enantioselective preparation of 3,4,5-trisubstituted 4,5-dihydroisoxazoles and their stereoselective elaboration of 5-side chain

Article abstract of DOI:10.1016/S0040-4020(02)01255-3

The magnesium ion-induced nitrile oxide cycloaddition to chiral α-silylallyl alcohols was examined. Treatment of chiral allyl alcohol with nitrile oxide in the presence of magnesium cation resulted in the smooth progress of the 1,3-dipolar cycloaddition to give optically active 4,5-dihydroisoxazoles in good yields. The present procedure serves as a good method for the preparation of multi-substituted 4,5-dihydroisoxazoles with high enantiomeric excess. When exposed to tetrabutylammonium fluoride (TBAF), the cycloadducts were converted into 4-substituted-5,6-dihydro-4H-[1,2]-oxazines in good yields without loss of optical purity. Acylsilanes, obtained by the oxidation of the cycloadduct, underwent stereoselective allylation reaction induced by Lewis acid to accomplish the elongation of C5-side chain in a stereoselective manner.

Full text of DOI:10.1016/S0040-4020(02)01255-3

Tetrahedron 58 (2002) 9613–9620
Enantioselective preparation of 3,4,5-trisubstituted
4,5-dihydroisoxazoles and their stereoselective elaboration
of 5-side chain
a
a
a
a
Akio Kamimura,a Yukio Kaneko, Ayaki Ohta, Kenji Matsuura, Yasuo Fujimoto,
,
*
Akikazu Kakehib and Shuji Kanemasac
aDepartment of Applied Chemistry, Faculty of Engineering, Yamaguchi University, Ube 755-8611, Japan
bDepartment of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, Nagano 380-8553, Japan
cInstitute of Advanced Material Study, Kyushu University, Kasuga 816, Japan
Received 6 September 2002; accepted 26 September 2002
Abstract—The magnesium ion-induced nitrile oxide cycloaddition to chiral a-silylallyl alcohols was examined. Treatment of chiral allyl
alcohol with nitrile oxide in the presence of magnesium cation resulted in the smooth progress of the 1,3-dipolar cycloaddition to give
optically active 4,5-dihydroisoxazoles in good yields. The present procedure serves as a good method for the preparation of multi-substituted
4,5-dihydroisoxazoles with high enantiomeric excess. When exposed to tetrabutylammonium fluoride (TBAF), the cycloadducts were
converted into 4-substituted-5,6-dihydro-4H-[1,2]-oxazines in good yields without loss of optical purity. Acylsilanes, obtained by the
oxidation of the cycloadduct, underwent stereoselective allylation reaction induced by Lewis acid to accomplish the elongation of C5-side
chain in a stereoselective manner. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
diisopinocampheylborane (DIP-Cl).6 Recently, we have
disclosed that chiral 3,4,5-trisubstituted-4,5-dihydroisoxa-
zoles are obtained through magnesium-mediated NOC
reaction to non-racemic a-silyl alcohols.7 In this paper,
we report full details of the methodology as well as
stereoserective elaboration of C5-side chain of the chiral
4,5-dihydroisoxazoles.
4,5-Dihydroisoxazoles are regarded as a useful synthetic
intermediate for constructing carbon-backbones because
they are converted to g-aminoalcohols or b-hydroxyketones
in one-step of reductive treatment,1 and this heterocycle has
often been used as key intermediates for the natural product
synthesis.2 Although the recent developments on the 1,3-
dipolar cycloaddition provides the preparation of enantio-
merically enriched cycloadducts,3 only limited numbers of
methods are available for the enantioselective nitrile oxide
cycloaddition (NOC) reaction.4 Compared with the Diels–
Alder reaction, the NOC reaction generally decreased the
reaction rate by the presence of Lewis acids and this poses a
significant problem for the NOC reaction as a tool for the
stereoselective synthesis. We have found the presence of
magnesium ion promotes the reaction smoothly and also
brings an excellent stereo/regio-selectivity for the reaction.5
This modification opens a practical aspect of the reaction to
prepare multi-substituted 4,5-dihydroisoxazoles that have
been regarded as a useful candidate for the construction of
acyclic carbon backbones. a-Silylallyl alcohols are readily
prepared from allylic alcohols and optically active ones are
available by a simple asymmetric reduction with B-chloro-
2. Results and discussion
Racemic a-silylallyl alcohols 2 were prepared in good
yields through the retro-Brock rearrangement of trimethyl-
silyl ether of allyl alcohol, which was generated in situ by
treatment of allyl alcohol 1 with base and TMSCl.8 To
convert racemic-2 to optically active 2, the alcohols were
oxidized to acylsilane 3, which were reduced with (2)-DIP-
Cl to give (S)-(2)-2 in 85–87% ee (Scheme 1).6
The 1,3-dipolar cycloaddition of nitrile oxides with 2 was
performed in the presence of magnesium cation
(Scheme 2).5 The results are summarized in Table 1.
Benzonitrile oxide in the presence of magnesium cation
underwent the smooth cycloaddition with 2a to give 4,5-
dihydroisoxazole 4a in 75% yield. The product contained
two diastereomers in the ratio of 94:6. The major
diastereomer showed positive optical rotation and its
Keywords: cycloadditions; asymmetric synthesis; enantioselection;
isoxazolines; oxazines.
*
Corresponding author. Tel.: þ81-836-35-9231; fax: þ81-836-35-9201;
e-mail: ak10@yamaguchi-u.ac.jp
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01255-3

9614
A. Kamimura et al. / Tetrahedron 58 (2002) 9613–9620
expected to have the same configuration in the three chiral
centers. The configuration was confirmed by the X-ray
crystallographic analysis performed on compound 4a, in
which newly formed chiral centers at C4 and C5 were both
assigned to be S.9
These stereochemical outcomes are easily understood by
comparison with the supposed reaction mechanism of the
magnesium-induced cycloaddition reaction (Scheme 3).
The oxygen atom in the nitrile oxide usually works as a
good Lewis base so that it undergoes coordination to
magnesium alkoxide under the present reaction conditions.
The magnesium alkoxide includes the dipolarophile unit so
that the dipole and the dipolarophile are placed close and the
reaction rate is enhanced. During the reaction process, there
exists the two possible transition states, TS-A and TS-B, but
due to the steric interaction between the TMS group and the
vinylic proton, TS-B should be disfavored. Thus, the
reaction proceeded through TS-A which furnishes syn-
cycloadducts in an enantioselective manner.10
Scheme 1.
We then examined to remove the TMS group. It is known
that a-silyl alcohol is converted to alcohols by treatment
with tetrabutylammonium fluoride (TBAF).11 We assumed
Scheme 2.
Table 1. Preparation of chiral 4,5-dihydroisoxazoles 4
Entry
R1
2
ee (%)
R2
Product
Yield (%)a
Ratiob
eeb
[a]D
1
2
3
4
5
6
7
C3H7–
C3H7–
C3H7–
C3H7–
Me
2a
2a
2a
2a
2b
2b
2b
87
87
87
87
85
85
81
Ph
4a
4b
4c
4d
4e
4f
75
52
32
40
59
58
45
94:6
97:3
98:2
99:1
94:6
95:5
99:1
82
84
78
83
80
80
75
þ130.4
þ124.8
þ124.9
þ91.0
p-Cl–C6H4–
p-CF3–C6H4–
PhCH2CH2–
Ph
p-Cl–C6H4–
p-CF3–C6H4–
þ113.3
þ121.9
þ99.0
Me
Me
4g
a
Isolated yield.
Determined by HPLC analyses.
b
HLPC analysis with ChiralPak AD indicated 82% ee (entry
1). The cycloaddition of other aromatic as well as aliphatic
nitrile oxides also gave optically active 4,5-dihydro-
isoxazoles 4 in good enatiomeric excesses (entry 2–4).
All the adducts showed dextrorotatory so that they all were
that this procedure would be useful to remove the silyl
group and examined these conditions to 4 (Scheme 4). The
starting cycloadduct 4a disappeared smoothly by
treatment with TBAF but the obtained product was found
to be 4-substituted-5,6-dihydro-4H-[1,2]-oxazine 5a,12
different from the expected 4,5-dihydroisoxazole. The
results are summarized in Table 2.
The present conversion of 4 to 5 proceeded in a spot-to-spot
manner. The oxazine 5a contained a pair of diastereomers
whose ratio was almost 2:1 due to its hemiacetal structure.
To check optical purity of 5a, PCC oxidation was carried
out; [1,2]-oxazin-3-one 6a was isolated in 67% yield.
Compound 6a showed dextrorotatory and its HPLC analysis
with ChiralPak AD revealed that 6a still maintained 81% ee.
Thus, no significant racemization had taken place during
Scheme 3.
Scheme 4.

A. Kamimura et al. / Tetrahedron 58 (2002) 9613–9620
Table 2. Conversion of 4 to [1,2]-oxazine 5 and [1,2]-oxazin-3-one 6
9615
According to the mechanism reported previously,11 the first
step of the reaction is deprotonation of 4a by fluoride anion
to form an alkoxide, which then attacks the TMS group
intramolecularly (intermediate A). Through this process the
TMS group migrates to the oxygen atom and a-hydroxy-
carbanion is then generated (intermediate B). E1CB-type
b-elimination from B cleaves C–O bond of the 4,5-
dihydroisoxazole to give alkoxide C, the oxy-anion of
which attacks the formyl unit in D, generated from keto–
enol tautomerism, to give [1,2]-oxazine structure 5. It
should be remarked that this ring enlargement only occurred
under anhydrous conditions; treatment of 4a with TBAF in
wet-THF resulted in no reaction and starting material 4a
was totally recovered (Scheme 6).
Entry
R1
R2
Yield (%)a
eeb
[a]D
5
6
1
2
3
4
C3H7–
C3H7–
Me
Ph
5a; 100
5b; 92
5c; 86
5d; 76
6a; 67
5b; 80
6c; 56
6d; 77
81
82
73
75
þ55.1
þ37.1
þ33.7
þ18.3
p-Cl–C6H4–
Ph
p-CF3–C6H4–
Me
a
Isolated yield.
Determined by HPLC analyses.
b
We next attempted carbon-chain elaboration reaction at C5
position of the ring. The Swern oxidation converted
compounds 4 into acylsilanes 8, which were regarded as
an equivalent of 4,5-dihydroisoxazole-5-carbaldehyde. The
nucleophilic addition to the aldehydes provides a useful
stereoselective carbon–carbon bond forming methodology
if the 4,5-dihydroisoxazole ring offers sufficient steric bias
for the stereoselection. With this strategy, the stereo-
selective carbon-chain elaboration at C3 position was
successfully achieved by Wade13 and our group.14 4,5-
Dihydroisoxazole-5-carbaldehydes, on the other hand, was
very difficult to isolate and purify so that use of them to
further transformation was not easy as well as the
stereoselection level was moderate.15 Thus, the acylsilane
is regarded as a good candidate for an equivalent of the
aldehydes.11d,16
Scheme 5.
Scheme 6.
The allylation reaction to acylsilane 8 was examined under
Lewis acidic conditions (Scheme 7). The results are
summarized in Table 3.
To a solution of 8a in CH2Cl2, allyltributyltin and TiCl4 was
added at 2788C and allylation product 9a was isolated in
88% yield (entry 1). The product contained almost a single
isomer of compound 9a and HPLC analysis indicated that
its ratio was 4/96. The same isomer of 9a was formed in the
reaction catalyzed by BF3·OEt2, while a diastereomeric
mixture of 9a was obtained from the reaction promoted by
SnCl4 (entry 2 and 3). Methacryltin also gave adduct 9b in
good yield. The stereoselectivity was better than the
reaction with allyltin (entry 4 and 5). Absence of an alkyl
substituent at C4 in 4,5-dihydroisoxazole reduced the
selectivity about 1/9–2/8 level (entry 6 and 7).
Scheme 7.
these transformation. Other chiral isoxazoles 4 were
converted into 6 by these treatments (entry 2–4).
Supposed mechanism of the conversion of 4,5-dihydro-
isoxazole 4 to [1,2]-oxazine 5 is depicted in Scheme 5.
The configuration at newly formed chiral center was
Table 3. Allylation of acylsilane 8
Entry
R
R1
8
Lewis acid
Time (h)
9; Yield (%)a
syn/antib
[a]D
1
2
3
4
5
6
7
C3H7–
C3H7–
C3H7–
C3H7–
C3H7–
H
H
H
H
Me
Me
H
8a
8a
8a
8a
8a
8c
8c
TiCl4
2.5
5
4.5
3.5
15.5
2
9a; 88
9a; 83
9a; 84
9b; 75
9b; 62
9c; 79
9c; 92
4/96
7/93
63/37
1/99
8/92
þ125.8
þ119.4
þ102.7
þ105.3
BF3·OEt2
SnCl4
TiCl4
BF3·OEt2
TiCl4
BF3·OEt2
þ106.4
c
20/80
10/90
c
H
H
2
a
Isolated yield.
Determined by HPLC analyses.
Starting from racemate.
b
c

9616
A. Kamimura et al. / Tetrahedron 58 (2002) 9613–9620
3.1.1. Preparation of 1-trimethylsilyl-2-hexen-1-ol [2a].
General procedure. To a solution of trans-2-hexene-1-ol
(6.762 g, 67.5 mmol) in THF (100 mL) was added n-BuLi
(1.6 M, 45 mL, 72 mmol) at 2788C over 5 min. and the
reaction mixture was allowed to stir for 1 h. TMSCl was
added to the solution and the reaction mixture was
maintained at the same temperature for additional 2.5 h.
sec-BuLi (0.99 M, 82 mL, 81.2 mmol) was added to the
solution at 2788C over 10 min and the resulting mixture
was allowed to stir at the same temperature for 2 h. Aqueous
NH4Cl (50 mL) was added to the solution and THF was
removed in vacuo. The resulting biphasic mixture was
extracted with ether (3£30 mL) and combined organic
phase was dried over Na2SO4. After filtration, ether was
removed in vacuo and the residue was subjected to flash
chromatography (hexane–ethyl acetate 10:1 then 3:1 v/v) to
give 1-trimethylsilyl-2-hexene-1-ol 2a in 68% yield
Scheme 8.
determined to be anti on the basis of an X-ray crystal-
lographic analysis for compound 9c.17 Based on a similar
NMR and HPLC behavior, we concluded all of 9 have the
same configuration.
1
(7.965 g, 46.2 mmol) as a yellow oil. H NMR (270 MHz,
CDCl3) d 0.03 (s, 9H), 0.89 (t, J¼7.3 Hz, 3H), 1.22–1.51
(m, 2H), 2.02 (q, J¼7.0 Hz, 2H), 3.89 (dd, J¼0.9, 6.3 Hz,
1H), 5.47 (dd, J¼6.3, 15.1 Hz, 1H), 5.58 (dt, J¼6.3,
It is interesting that the stereoselectivity of the reaction was
independent to the sorts of Lewis acid. This is probably due
to steric congestion led by trimethylsilyl group at the
acylsilane unit that prevents the chelation-type activation.
As a result, the reaction should proceed via the Felkin–Ahn
type transition state regardless of Lewis acid employed.
Scheme 8 shows the likely transition state of the reaction.
Nucleophilic attack should occur from the less hindered side
(right side of acylsilane unit) to give anti adduct selectively.
If C4 substituent, R, is absent, the chelation type activation
is now possible for the reaction catalyzed by TiCl4 so the
diastereoselectivity decreases (Table 3, entry 6). The
observed less selectivity by SnCl4 is likely explained in
the same reason (Table 3, entry 3).
15.5 Hz, 1H). IR: 3650–3100 cm21
.
3.1.2. 1-Trimethylsilyl-2-buten-1-ol [2b]. Compound 2b
1
was prepared in a similar way as 2a. Yellow oil. H NMR
(270 MHz, CDCl3) d 0.03 (s, 9H), 1.72 (dd, J¼1.3, 5.9 Hz,
3H), 3.89 (td, J¼1.3, 6.6 Hz, 1H), 5.42–5.66 (m, 2H). 13C
NMR (67.5 MHz, CDCl3) d 24.2, 17.8, 68.4, 122.4, 132.3.
IR: 3650–3100 cm21
.
3.1.3. Oxidation of silyl alcohol 2. Preparation of
1-trimethylsilyl-2-hexen-1-one [3a]. General procedure.
To a solution of oxalyl chloride (2.4 mL, 27.5 mmol) in
CH2Cl2 (20 mL) was added DMSO (3.7 mL, 52.1 mmol) at
2788C over 10 min. After 1.5 h, a solution of 2a (3.150 g,
18.3 mmol) in CH2Cl2 (30 mL) was added to the reaction
mixture and the resulting solution was allowed to stir at
2788C for 2 h. Et3N (13.4 mL, 96.1 mmol) was added to the
reaction mixture and the resulting mixture was allowed to
warm to 08C for 2.5 h. The reaction mixture was poured into
water (50 mL) and the water phase was extracted with
CH2Cl2 (3£30 mL). The combined organic phase was
washed with dil HCl (3£20 mL) and dried over Na2SO4.
After filtration and removal of solvent, crude product was
purified through flash chromatography (hexane–ether 15:1
v/v) to give 3a in 95% yield (2.861 g, 16.8 mmol). Yellow
oil. 1H NMR (270 MHz, CDCl3) d 0.26 (s, 9H), 0.90 (t, 3H,
J¼7.3 Hz), 1.55–1.75 (m, 2H), 2.24 (dq, 2H, J¼1.3,
6.9 Hz), 6.24 (tq, 1H, J¼1.4, 6.9 Hz), 6.76 (tq, 1H, J¼6.9,
16.2 Hz). 13C NMR (67.5 MHz, CDCl3) d 21.5, 14.1, 21.9,
35.2, 137.1, 149.2. IR (neat) n 3050–2750, 1640,
In conclusion, we have developed a new facile method to
prepare optically active 3,4,5-multisubstituted 4,5-dihydro-
isoxazoles in a short step. The reaction was well-controlled
by the presence of magnesium cation and high enantio-
selectivity was achieved. Obtained isoxazoles were readily
converted into [1,2]-oxazines without loss of optical purity
at C4. Elaboration of C5 side chain was also accomplished
in a highly selective level. As the 4,5-dihydroisoxazole
chemistry is directly connected to the construction of open-
chain carbon backbones, this method will provide a useful
method in organic synthesis.
3. Experimental
3.1. General
1250 cm21
.
All 1H and 13C NMR spectra were measured in CDCl3 and
recorded on JEOL EX-270 (270 MHz for 1H and 67.5 MHz
1
for 13C) or Brucker Advance 400 (400 MHz for H and
3.1.4. 1-Trimethylsilyl-2-buten-1-one [3b]. Compound 3b
was prepared in a similar way as 3a. Bp 75–908C/5 mmHg.
1H NMR (270 MHz, CDCl3) d 0.24 (s, 9H), 1.93 (dd, 3H,
J¼1.5, 6.8 Hz), 6.24 (qd, 1H, J¼1.7, 16.2 Hz), 6.82 (qd, 1H,
J¼6.8, 16.2 Hz). 13C NMR (67.5 MHz, CDCl3) d 22.0,
18.6, 138.1, 143.8. IR (neat) n 3050–2850, 1630,
100 MHz for 13C) spectrometer. All the reactions in this
paper were performed under nitrogen atmosphere. All of
reaction solvents were dried over appropriate drying agents
(K for THF and CaH2 for all other solvents) and distilled
under nitrogen before use. Allyl alcohols were purified by
distillation. Hydroxymoyl chrolides were prepared by
literature method.18 sec-BuLi was purchased from Kanto
Kagaku and methylmagnesium bromide in ether solution
was purchased from Aldrich.
1240 cm21
.
3.1.5. Asymmetric reduction of 3a. Preparation of trans-
1-trimethylsilyl-2-hexen-1-ol [(2)-2a]. General procedure.

A. Kamimura et al. / Tetrahedron 58 (2002) 9613–9620
9617
To a solution of (2)-DIP-Cl (3.868 g, 12.1 mmol) in THF
(10 mL) at 2108C was added a solution of 3a (1.288 g,
7.58 mmol) in THF (10 mL) and the reaction mixture was
allowed to stir for 20 h at 2108C. The reaction solvent was
removed in vacuo, and diethanolamine (3.780 g, 36.0 mmol)
in ether (50 mL) was added to the residue. The mixture was
allowed to stir for 24 h at room temperature. Precipitate was
removed by filtration and the residue was subjected to flash
chromatography (hexane–ethyl acetate 15:1 v/v) to give (2)-
2a in 75% yield (0.972 g, 5.65 mmol). [a]D¼231.0 (c 1.07,
CHCl3). 87% ee.
NMR (270 MHz, CDCl3) d 0.19 (s, 9H), 0.93 (t, 3H,
J¼7.0 Hz), 1.26–1.43 (m, 2H), 1.51–1.75 (m, 3H), 3.24–
3.27 (br, 1H), 3.73 (ddd, 1H, J¼3.6, 4.9, 8.6 Hz), 4.62 (dd,
1H, J¼4.3, 4.9 Hz), 7.66 (m, 2H), 7.76 (m, 2H). 13C NMR
(67.5 MHz, CDCl3) d 23.0, 14.0, 19.8, 33.4, 48.4, 68.3,
89.5, 121.8, 125.6, 127.1, 131.3, 132.6, 159.5. IR (neat) n
3640–3100, 3000–2700, 1610, 1320, 1130 cm21. HRMS
(FAB) calcd for (MþH) C17H25F3NO2Si: 360.1604, found
360.1609.
3.2.4. (4S,5S)-5-[(S)-Hydroxy(trimethylsilyl)methyl]-3-
(2-phenylethyl)-4-propyl-4,5-dihydroisoxazole [(1)-4d].
[a]D¼þ91.0 (c 1.15, CHCl3). 83% ee. 1H NMR (270 MHz,
CDCl3) d 0.18 (s, 9H), 0.99 (t, 3H, J¼7.1 Hz), 1.27–1.72
(m, 4H), 2.56 (q, 2H, J¼7.6 Hz), 2.74 (dq, 2H, J¼7.0,
9.2 Hz), 2.91–3.07 (m, 3H), 3.15–3.24 (m, 3H), 3.69 (s,
1H), 4.38 (dd, 1H, J¼4.0, 7.0 Hz), 7.24–7.38 (m, 5H). 13C
NMR (67.5 MHz, CDCl3) d 23.2, 14.1, 19.9, 28.2, 32.2,
33.5, 50.4, 67.1, 87.2, 126.2, 128.2, 128.4, 140.7, 162.0. IR
(neat) n 3600–3100, 3000–2700, 1600, 1240 cm21. HRMS
(EI) calcd for (Mþ) C18H29NO2Si: 319.1966, found
319.1969.
trans-1-Trimethylsilyl-2-butene-1-ol (2)-2b was prepared
in a similar way: [a]D¼230.3 (c 0.97, CHCl3). 85% ee.
3.2. Magnesium ion-induced enantioselective 1,3-dipolar
cycloaddition to 2
3.2.1. (4S,5S)-5-[(S)-Hydroxy(trimethylsilyl)methyl]-3-
phenyl-4-propyl-4,5-dihydroisoxazole [(1)-4a]. General
procedure. Methylmagnesium bromide (3 M in ether,
1.0 mL, 3 mmol) was added to a solution of BuOH
(0.227 g, 3.06 mmol) in CH2Cl2 (10 mL). The reaction
solution was cooled to 2788C and (2)-3a (0.266 g,
1.55 mmol) was added. Then benzenehydroximoyl chrolide
(0.403 g, 2.58 mmol) in CH2Cl2 (15 mL) and Et3N (0.276 g,
2.73 mmol) was added in this order. The reaction mixture
was allowed to warm to room temperature for 17 h.
NH4Claq (15 mL) was added and the resulting biphasic
mixture was extracted with CH2Cl2 (3£10 mL). The organic
phases were combined and dried over Na2SO4. After
filtration and removal of solvent, the crude product was
purified through flash chromatography (hexane–ethyl
acetate 15:1 then 1:1 v/v) to give (þ)-4a in 75% (0.260 g,
0.89 mmol). [a]D¼þ130.4 (c 1.00, CHCl3). 82% ee 1H
NMR (270 MHz, CDCl3) d 0.18 (s, 9H), 0.92 (t, 3H,
J¼7.3 Hz), 1.26–1.44 (m, 2H), 1.51–1.68 (m, 2H), 1.71 (d,
1H, J¼7.9 Hz), 3.26 (dd, 1H, J¼4.8, 7.8 Hz), 3.67 (td, 1H,
J¼4.3, 8.6 Hz), 4.58 (t, 1H, J¼4.8 Hz), 7.39–7.42 (m, 3H),
7.63–7.66 (m, 2H). 13C NMR (67.5 MHz, CDCl3) d 23.0,
14.0, 19.9, 33.4, 48.8, 68.0, 88.7, 126.9, 128.8, 129.0, 129.9,
160.6. IR (neat) n 3630–3130, 3000–2750, 1590, 1440,
1250 cm21. Anal. calcd for C16H25NO2Si: C, 65.93; H,
8.65; N, 4.81. Found: C, 65.95; H, 8.58; N, 5.02.
3.2.5. (4S,5S)-5-[(S)-Hydroxy(trimethylsilyl)methyl]-4-
methyl-3-phenyl-4,5-dihydroisoxazole [(1)-4e]. [a]D¼
þ113.3 (c 1.03, CHCl3), 80% ee. 1H NMR (270 MHz,
CDCl3) d 0.18 (s, 9H), 1.32 (d, 3H, J¼6.9 Hz), 1.65 (d, 1H,
J¼6.6 Hz), 3.32 (t, 1H, J¼6.0 Hz), 3.69 (quint, 1H,
J¼6.9 Hz), 4.44 (t, 1H, J¼5.6 Hz), 7.38–7.45 (m, 3H),
7.73–7.68 (m, 2H). 13C NMR (67.5 MHz, CDCl3) d 23.1,
17.3, 43.3, 66.3, 91.0, 126.9, 128.7, 129.8, 161.5. IR (neat) n
3650–3150, 3030–2700, 1600, 1250 cm21. Anal. calcd for
C14H21NO2Si: C, 63.84; H, 8.04; N, 5.32. Found: C, 63.83;
H, 8.25; N, 5.11.
3.2.6. (4S,5S)-3-(4-Chlorophenyl)-5-[(S)-hydroxy(tri-
methylsilyl)methyl]-4-methyl-4,5-dihydro-isoxazole
[(1)-4f]. [a]D¼þ121.9 (c 0.86, CHCl3). 80% ee. 1H NMR
(270 MHz, CDCl3) d 0.18 (s, 9H), 1.31 (d, 3H, J¼7.3 Hz),
1.80–2.03 (br, 1H), 3.31 (d, 1H, J¼5.0 Hz), 3.68 (quint, 1H,
J¼7.1 Hz), 4.45 (dd, 1H, J¼5.0, 6.0 Hz), 7.38 (m, 2H), 7.58
(m, 2H). 13C NMR (67.5 MHz, CDCl3) d 23.2, 17.10, 42.8,
66.2, 91.2, 127.1, 127.9, 128.7, 135.4, 160.3. IR (neat) n
3650–3150, 3030–2700, 1590, 1240 cm21. Anal. calcd for:
C14H20ClNO2Si: C, 56.45; H, 6.77; N, 4.70. Found: C,
56.18; H, 6.93; N, 4.60.
Other cycloaddition reactions were carried out in a similar
manner.
3.2.7. (4S,5S)-5-[(S)-Hydroxy(trimethylsilyl)methyl]-4-
methyl-3-[4-(trifluoromethyl)phenyl]-4,5-dihydroisoxa-
3.2.2. (4S,5S)-3-(4-Chlorophenyl)-5-[(S)-hydroxy(tri-
methylsilyl)methyl]-4-propyl-4,5-dihydroisoxazole [(1)-
4b]. [a]D¼þ124.8 (c 1.06, CHCl3). 84% ee. 1H NMR
(270 MHz, CDCl3) d 0.18 (s, 9H), 0.92 (t, 3H, J¼7.3 Hz),
1.26–1.43 (m, 2H), 1.50–1.69 (m, 2H), 1.65 (d, 1H, J¼
7.6 Hz), 3.25 (dd, 1H, J¼4.3, 7.9 Hz), 3.65 (ddd, 1H, J¼4.0,
5.0, 8.6 Hz), 4.58 (t, 1H, J¼4.8 Hz), 7.37 (m, 2H), 7.57 (m,
2H). 13C NMR (67.5 MHz, CDCl3) d 23.0, 14.0, 19.8, 33.4,
48.7, 68.1, 89.0, 127.5, 128.1, 129.0, 135.7, 159.6. IR (neat) n
3600–3100, 3000–2700, 1590, 1250 cm21. HRMS (FAB)
calcd for (MþH) C16H25ClNO2Si: 326.1343, found 326.1333.
1
zole [(1)-4g]. [a]D¼þ99.0 (c 0.90, CHCl3). 75% ee. H
NMR (270 MHz, CDCl3) d 0.19 (s, 9H), 1.6–1.8 (br, 1H),
1.33 (d, 3H, J¼6.9 Hz), 3.33 (br, 1H), 3.75 (quint, 1H,
J¼6.9 Hz), 4.49 (dd, 1H, J¼4.6, 6.3 Hz), 7.66 (m, 2H), 7.76
(m, 2H). 13C NMR (67.5 MHz, CDCl3) d 23.1, 17.2, 43.0,
66.7, 91.8, 125.7, 127.2, 130.4, 132.4, 160.5. IR (neat) n
3650–3130, 3130–2750, 1610, 1240 cm21. HRMS (FAB)
calcd for (MþH) C15H21F3NO2Si: 332.1294, found
332.1293.
3.2.8. Cleavage of the isoxazole ring by TBAF. Prepar-
ation of (4S)-3-phenyl-4-propyl-5,6-dihydro-4H-
3.2.3. (4S,5S)-5-[(S)-Hydroxy(trimethylsilyl)methyl]-4-
propyl-3-[4-(trifluoromethyl)phenyl]-4,5-dihydroisoxa-
[1,2]oxazin-6-ol [(1)-5a]. General procedure. To
a
1
zole [(1)-4c]. [a]D¼þ124.9 (c 0.54, CHCl3). 78% ee. H
solution of (þ)-4a (0.726 g, 2.51 mmol) in THF (10 mL)

9618
A. Kamimura et al. / Tetrahedron 58 (2002) 9613–9620
was added TBAF (1.0 M, 2.7 mL, 2.7 mmol) and the
resulting solution was allowed to stir at room temperature
for 40 h. Solvent was removed in vacuo and the residue was
subjected to flash chromatography (hexane–ethyl acetate
3:1 then 1:1 v/v) to give 5a in 100% yield (0.547 g,
2.50 mmol). Pale yellow oil. [a]D¼þ38.8 (c 1.29, CHCl3).
1H NMR (270 MHz, CDCl3) d 0.80 (t, 3H, J¼7.1 Hz),
1.17–1.66 (m, 4H), 1.87–2.16 (m, 2H), 2.83–2.89 (m, 1H,
4-H minor isomer), 3.02 (m, 1H, 4-H major isomer), 3.10–
3.40 (br, 1H), 5.47 (dd, 1H, J¼3.0, 5.6 Hz, minor isomer),
5.52 (dd, 1H, J¼3.3, 4.3 Hz, major isomer), 7.36–7.51 (m,
3H), 7.51–7.56 (m, 2H). 13C NMR (67.5 MHz, CDCl3) d
major; 13.7, 19.4, 28.3, 29.5, 34.3, 91.1, 126..6, 128.3, 129.1,
135.1, 162.0. Minor, 13.3, 19.6, 29.3, 29.7, 34.2, 92.4, 126.7,
128.4, 129.2,.135.1, 161.9. IR (neat) n: 3700–3100, 3000–
2700, 1590, 1430, 1270 cm21. Anal. calcd for C13H17NO2: C,
71.21; H, 7.18; N, 6.39. Found: C, 70.77; H, 7.91; N, 6.34.
General procedure. To a suspension of PCC (0.112 g,
0.52 mmol) in CH2Cl2 was added (þ)-5a (0.158 g,
0.72 mmol) in CH2Cl2 (10 mL) and the reaction mixture
was allowed to stir at 08C for 1.5 h. The supernatant of the
reaction mixture was directly put through chromatography
(hexane–ethyl acetate 3:1 then 1:1) and desired 6a was
isolated in 67% yield (0.104 g, 0.48 mmol). Red oil.
[a]D¼þ55.1 (c 1.02, CHCl3). 81% ee. 1H NMR
(270 MHz, CDCl3) d 0.91 (t, 3H, J¼7.1 Hz,), 1.14–1.73
(m, 4H), 2.69 (dd, 1H, J¼5.9, 16.5 Hz), 2.85 (dd, 1H,
J¼1.8, 16.5 Hz), 3.28 (m, 1H), 7.44–7.55 (m, 3H), 7.74–
7.78 (m, 2H). 13C NMR (67.5 MHz, CDCl3) d 13.6, 19.8,
29.9, 32.6,33.8, 126.7, 128.9, 131.3, 131.6, 164.6, 169.1. IR
(neat) n 3000–2750, 1770, 1600, 1440, 1160 cm21. HRMS
(EI) calcd for (Mþ) C13H15NO2: 217.1087, found 217.1107.
Other oxazinones 6 were prepared in a similar manner.
Other oxazines were prepared in a similar manner.
3.2.13. (4S)-3-(4-Chlorophenyl)-4-propyl-4,5-dihydro-
[1,2]oxazin-6-one [(1)-6b]. Oil. [a]D¼þ37.1 (c 0.99,
1
3.2.9. (4S)-3-(4-Chlorophenyl)-4-propyl-5,6-dihydro-
4H-[1,2]oxazin-6-ol [(1)-5b]. Pale yellow oil. [a]D
þ34.9 (c 0.63, CHCl3). 1H NMR (270 MHz, CDCl3) d
0.81–0.93 (m, 3H), 1.21–1.92 (m, 4H), 1.92–1.97 (m, 1H),
2.07–2.18 (m, 1H), 2.77–2.81 (m, 1H, minor isomer),
2.93–3.02 (m, 1H, major isomer), 5.45 (dd, 1H, J¼3.0,
4.6 Hz, minor isomer), 5.51 (dd, 1H, J¼3.6, 7.3 Hz, major
isomer), 7.35–7.51 (m, 4H). 13C NMR (67.5 MHz, CDCl3) d
major; 13.1, 19.3, 28.1, 29.6, 34.4, 91.1, 128.0, 128.0, 128.6,
133.5, 135.1, 160.9. Minor; 15.1, 19.5, 29.1, 30.6, 34.0, 92.4,
127.1, 128.4, 128.6, 133.5, 135.2, 160.8. IR (neat) n 3700–
3000, 3000–2750, 1590, 1220 cm21. HRMS (EI) calcd for
(Mþ) C13H16ClNO2: 253.0869, found 253.0870.
CHCl3). 82% ee. H NMR (270 MHz, CDCl3) d 0.91 (t,
3H, J¼7.1 Hz,), 1.19–1.39 (m, 1H), 1.40–1.70 (m, 3H),
2.69 (dd, 1H, J¼5.9, 16.5 Hz), 2.85 (dd, 1H, J¼1.8,
16.5 Hz), 3.28 (dtd, 1H, J¼1.8, 6.3, 10.6 Hz), 7.45 (m,
2H), 7.70 (m, 2H). 13C NMR (67.5 MHz, CDCl3) d 13.6,
19.8, 29.8, 32.5,33.7, 128.0, 129.2, 130.1, 137.5, 163.6,
168.7. IR (neat) n: 1780, 1260 cm21. Anal. calcd for
C13H14ClNO3: C, 62.03; H, 5.61; N, 5.56. Found: C, 62.41;
H, 5.88; N, 5.14.
3.2.14. (4S)-4-Methyl-3-phenyl-4,5-dihydro-[1,2]oxazin-
6-one [(1)-6c]. Oil. [a]D¼þ33.7 (c 1.04, CHCl3). 74% ee.
1H NMR (270 MHz, CDCl3) d 1.33 (d, 3H, J¼7.2 Hz), 2.71
(dd, 1H, J¼3.0, 16.5 Hz), 2.79 (dd, 1H, J¼5.4, 16.8 Hz),
3.43 (ddq, 1H, J¼2.6, 5.4, 7.2 Hz), 7.44–7.55 (m, 3H),
7.75–7.79 (m, 2H). 13C NMR (67.5 MHz, CDCl3) d 16.9,
29.5, 32.6, 127.0, 129.3, 131.7, 165.1, 169.2. IR (neat) n
1780, 1440, 1260 cm21. HRMS (EI) calcd for (Mþ)
C11H11NO2: 189.0804, found 189.0786.
3.2.10. (4S)-4-Methyl-3-phenyl-5,6-dihydro-4H-[1,2]oxa-
zin-6-ol [(1)-5c]. Pale yellow oil. [a]D¼þ36.2 (c 1.00,
CHCl3). 1H NMR (270 MHz, CDCl3) d 1.10 (d, 3H,
J¼7.3 Hz, major isomer), 1.24 (d, 3H, J¼7.3 Hz, minor
isomer), 1.82–2.05 (m, 2H), 2.95 (m, 1H, minor isomer),
3.13 (m, 1H, J¼7.3 Hz, major isomer), 3.4–3.8 (br, 1H),
5.50–5.55 (m, 1H), 7.37–7.41 (m, 3H), 7.51–7.60 (m, 2H).
13C NMR (67.5 MHz, CDCl3) d major; 18.8, 23.3, 32.5,
91.0, 126.8, 128.4, 129.2, 161.8. Minor; 19.7, 24.1, 31.4,
91.3, 126.6, 128.5, 129.4, 161.8. IR (neat) n 3650–3050,
3000–2750, 1590, 1440 cm21. HRMS (EI) calcd for (Mþ)
C11H13NO2: 191.0946, found 191.0946.
3.2.15. (4S)-4-Methyl-3-[4-(trifluoromethyl)phenyl]-4,5-
dihydro-[1,2]oxazin-6-one [(1)-6d]. White solid. [a]D¼
þ18.3 (c 1.23, CHCl3). 74% ee. 1H NMR (270 MHz,
CDCl3) d 1.35 (d, 3H, J¼7.6 Hz), 2.74 (dd, 1H, J¼3.0,
16.5 Hz), 2.82 (dd, 1H, J¼5.0, 17.2 Hz), 3.43 (ddq, 1H,
J¼3.0, 5.0, 7.6 Hz), 7.44 (m, 2H), 7.90 (m, 2H). 13C NMR
(67.5 MHz, CDCl3) d 16.5, 29.1, 32.0, 125.9, 125.9, 127.1,
134.8, 163.5, 168.3. IR (neat) n 1760, 1440, 1260 cm21
.
HRMS (EI) calcd for (Mþ) C12H10F3NO2: 257.0658, found
257.0666.
3.2.11. (4S)-4-Methyl-3-[4-(trifluoromethyl)phenyl]-5,6-
dihydro-4H-[1,2]oxazin-6-ol [(1)-5d]. Pale yellow oil.
[a]D¼þ33.2 (c 1.06, CHCl3). 1H NMR (270 MHz, CDCl3)
d 1.10 (d, 3H, J¼7.3 Hz, major isomer), 1.26 (t, 3H,
J¼7.3 Hz, minor isomer), 1.83–2.06 (m, 2H), 2.17–2.32
(m, 1H), 2.95 (dq, 1H, J¼4.5, 7.8 Hz, minor isomer), 3.13
(m, 1H, J¼7.3 Hz, major isomer), 5.55 (dd, 1H, J¼2.6,
4.0 Hz, major isomer), 5.59 (t, 1H, J¼3.3, minor isomer),
7.67 (m, 4H). 13C NMR (67.5 MHz, CDCl3) d major; 18.5,
23.3, 32.3, 91.2, 125.3, 125.3, 127.1, 131.0, 138.4, 160.7.
Minor; 20.6, 24.7, 31.6, 91.7, 121.9, 125.9, 138.4, 160.4. IR
(neat) n 3650–3050, 3000–2750, 1260 cm21. HRMS (EI)
calcd for (Mþ) C12H12F3NO2: 259.0830, found 259.0817.
3.2.16. Preparation of (3-phenyl-4-propyl-4,5-dihydro-
isoxazol-5-yl)-trimethylsilanylmethanone [(1)-8a]. This
preparation was carried out in a similar manner to the
oreparation of 3. Pale yellow oil. [a]D¼þ114.7 (c 1.31,
CHCl3). 1H NMR (270 MHz, CDCl3) d 0.27 (s, 9H), 0.92 (t,
3H, J¼7.3 Hz), 1.32–1.41 (m, 2H), 1.50–1.69 (m, 2H),
3.85 (td, 1H, J¼3.6, 8.6 Hz), 4.65 (d, 1H, J¼3.6 Hz), 7.40–
7.43 (m, 3H), 7.64–7.78 (m, 2H). 13C NMR (67.5 MHz,
CDCl3) d 22.8, 13.6, 19.8, 33.0, 48.6, 94.4, 127.1, 128.2,
128.8, 130.1, 160.6. IR (neat) n 3000–2700, 1720, 1630,
1430, 1240 cm21. Anal. calcd for C16H23NO2Si: C, 66.39;
H, 8.01; N, 4.48. Found: C, 66.27; H, 7.98; N, 4.77.
3.2.12. Oxidation to oxazinone 6. Preparation of (4S)-3-
phenyl-4-propyl-4,5-dihydro-[1,2]oxazin-6-one [(1)-6a].

A. Kamimura et al. / Tetrahedron 58 (2002) 9613–9620
9619
3.2.17. Allylation reaction of 8. Preparation of (4S,5S)-5-
[(1R)-1-hydroxy-1-trimethylsilyl-3-butenyl]-3-phenyl-4-
propyl-4,5-dihydroisoxazole [(1)-9a]. General procedure.
To a solution of (þ)-8a (0.801 g, 2.77 mmol) in CH2Cl2
(10 mL) at 2788C, ally tributyltin (1.816 g, 5.49 mmol) and
TiCl4 (0.31 mL, 2.82 mmol)wereadded.Thereactionmixture
was allowed to warm to room temperature over 18 h. dil HCl
(5 mL) was added to the mixture and the resulting biphasic
solution was extracted with CH2Cl2 (3£20 mL). The organic
phase was combined and dried over Na2SO4. After filtration
and removal of solvent. The crude product was purified
through flash chromatography (hexane–ethyl acetate 15:1) to
give 9a in 88% yield (0.811 g, 2.44 mmol). Colorless oil.
[a]D¼þ125.8 (c 0.93, CHCl3). 1H NMR (270 MHz, CDCl3) d
0.19 (s, 9H), 0.87 (t, 3H, J¼7.1 Hz), 1.17–1.74 (m, 5H), 2.36
(dd, 1H, J¼8.0, 14.5 Hz), 2.45 (dd, 1H, J¼6.8, 14.5 Hz), 3.90
(td, 1H, J¼4.0, 6.9 Hz), 4.63 (d, 1H, J¼4.0 Hz), 5.17 (dd, 1H,
J¼1.6, 15.8 Hz), 5.16 (dd, 1H, J¼1.2, 12.5 Hz), 5.78–5.93
(m, 1H), 7.39–7.41 (m, 3H), 7.65–7.69 (m, 2H). 13C NMR
(67.5 MHz, CDCl3) d 22.1, 14.1, 19.2, 33.4, 39.2, 46.1, 70.8,
91.2, 118.9, 127.0, 128.7, 128.9, 129.8, 133.1, 160.5. IR (neat)
R value was 0.0586. Details are available from Cambridge
Crystalographic Data Centre on request.9
3.4. X-Ray structural analysis for (5S p)-5-[(1R p)-1-
hydroxy-1-trimethylsilyl-3-butenyl]-3-phenyl-4,5-
dihydroisoxazole [9c]
Crystal data. C16H23NO2Si, M¼289.45, monoclinic,
˚
a¼6.938(5), b¼20.694(5), c¼11.863(4) A, b¼94.278(4),
3
˚
V¼1699(1) A , space group P21/a, Z¼4. 4324 of reflections
were collected and 1466 unique reflections were used. Final
R value was 0.0776. Details are available from Cambridge
Crystalographic Data Centre on request.17
References
1. For reviews on the chemistry of 4,5-dihydroisoxazole, see:
(a) Caramella, P.; Gru¨nanger, P. 1,3-Dipolar Cycloaddition
Chemistry, Padwa, A., Ed.; Wiley: New York, 1984; Vol. 1.
n 3640–3200, 3000–2750, 1640, 1590, 1440, 1240 cm21
.
¨
(b) Jager, V.; Grund, H.; Buß, V.; Schwab, W.; Muller, I. Bull.
¨
Anal. calcd for C19H29NO2Si: C, 68.54; H, 8.82; N, 4.22.
Found: C, 68.44; H, 9.12; N, 4.24.
Chem. Soc. Belg. 1983, 92, 1039–1054. (c) Kozikowski, A. P.
¨
Acc. Chem. Res. 1984, 17, 410–416. (d) Jager, V.; Grund, H.;
Franz, R.; Ehrler, R. Lect. Heterocycl. Chem. 1985, 8, 79–98.
(e) Torssell, K. B. G. Nitrile Oxides, Nitrones, and Nitronates
in Organic Synthesis. VCH Verlaggesellschaft mbH:
Weinheim, 1988. (f) Curran, D. P. Advances in Cycloaddition
Chemistry, Curran, D. P., Ed.; JAI: Greenwich, CT, 1988; Vol.
1, p 129. (g) Annunziata, R.; Cinquini, M.; Cozzi, F.;
Raimondi, L. Gazz. Chim. Ital. 1989, 119, 253–269.
(h) Padwa, A.; Schoffstall, A. M. Advances in Cycloaddition
Chemistry, Curran, D. P., Ed.; JAI: Greenwich, CT, 1990; Vol.
2, p 1. (i) Kanemasa, S.; Tsuge, O. Heterocycles 1990, 30,
719–736. (j) Kamimura, A. J. Synth. Org. Chem. Jpn 1992,
50, 808–825. (k) Kanemasa, S. J. Synth. Org. Chem. Jpn 1995,
53, 104–115. (l) Inomata, K.; Ukaji, Y. J. Synth. Org. Chem.
Jpn 1998, 56, 11–21.
Other compounds 9 were prepared in a similar manner.
3.2.18. (4S,5S)-5-[(1R)-1-Hydroxy-3-methyl-1-trimethyl-
silyl-3-butenyl]-3-phenyl-4-propyl-4,5-dihydroisoxazole
1
[(1)-9b]. Colorless oil. [a]D¼þ105.3 (c 1.01, CHCl3). H
NMR (270 MHz, CDCl3) d 0.14 (s, 9H), 0.87 (t, 3H,
J¼7.3 Hz), 1.24–1.68 (m, 5H), 1.93 (s, 3H), 2.39 (d, 1H,
J¼13.5 Hz), 2.44 (d, 1H, J¼14.2 Hz), 3.81 (q, 1H,
J¼5.3 Hz), 4.51 (d, 1H, J¼4.3 Hz), 4,81 (s, 1H), 4.98 (t,
1H, J¼2.0 Hz), 7.39–7.44 (m, 3H), 7.65–7.69 (m, 2H). 13C
NMR (67.5 MHz, CDCl3) d 22.1, 13.9, 18.9, 25.4, 34.1,
41.8, 47.8, 70.4, 91.1, 115.3, 126.8, 128.7, 129.0, 129.7,
142.5, 160.1. IR (neat) n 3640–3200, 3000–2750, 1640,
1590, 1440, 1240 cm21. HRMS (FAB) calcd for (MþH)
C20H32NO2Si: 346.2202, found 346.2203.
2. Recent examples: (a) Bode, J. W.; Carreira, E. M. J. Org.
Chem. 2001, 66, 6410–6424. (b) Bode, J. W.; Carreira, E. M.
J. Am. Chem. Soc. 2001, 123, 3611–3612. (c) Kim, D.; Lee, J.;
Shim, P. J.; Lim, J. I.; Doi, T.; Kim, S. J. Org. Chem. 2002, 67,
772–781. (d) Kim, D.; Lee, J.; Shim, P. J.; Lim, J. I.; Jo, H.;
Kim, S. J. Org. Chem. 2002, 67, 764–771. (e) Aungst, Jr.
R. A.; Chan, C.; Funk, R. L. Org. Lett. 2001, 3, 2611–2613.
(f) Smith, A. L.; Pitsions, E. N.; Hwang, C. K.; Mizuno, Y.;
Saimoto, H.; Scariato, G. R.; Suzuki, T.; Nicolaou, K. C. J. Am.
Chem. Soc. 1993, 115, 7612–7624. (g) Smith, A. L.; Hwang,
C. K.; Pitsions, E.; Scariato, G. R.; Nicolaou, K. C. J. Am.
Chem. Soc. 1992, 114, 3134–3136.
3.2.19. (5S p)-5-[(1R p)-1-Hydroxy-1-trimethylsilyl-3-
butenyl]-3-phenyl-4,5-dihydroisoxazole [9c]. White
1
solid. H NMR (270 MHz, CDCl3) d 0.10 (s, 9H), 1.50 (s,
1H), 2.15 (dd, 1H, J¼8.3, 13.9 Hz), 2.42 (dd, 1H, J¼6.9,
13.9 Hz), 3.03 (dd, 1H, J¼10.6, 16.5 Hz), 3.39 (dd, 1H,
J¼10.6, 16.5 Hz), 4.74 (dd, 1H, J¼6.6, 9.6 Hz), 5.01 (dd,
1H, J¼2.0, 9.3 Hz), 5.05 (dd, 1H, J¼1.3, 13.5 Hz), 5.63–
5.82 (m, 1H), 7.27–7.31 (m, 3H), 7.56–7.58 (m, 2H). 13C
NMR (67.5 MHz, CDCl3) d 22.4, 33.4, 40.5, 68.3, 87.0,
118.4, 126.6, 128.6, 129.6, 130.0, 133.1, 157.6. IR (neat) n
3. Gothelf, K. V.; Jørgensen, K. A. Chem. Rev. 1998, 98,
863–910.
3640–3200, 3000–2750, 1640, 1590, 1440, 1240 cm21
.
HRMS (FAB) calcd for (MþH) C16H24NO2Si: 290.1570,
4. For regio/stereoserective formation of 4,5-disubstituted-4,5-
dihydroisoxazoles: (a) Martin, S. F.; Dupre, B. Tetrahedron
¨
Lett. 1983, 24, 1337–1340. (b) Mu¨ller, I.; Jager, V.
found 290.1579.
3.3. X-Ray structural analysis for (4S,5S)-5-[(S)-
hydroxy(trimethylsilyl)methyl]-3-phenyl-4-propyl-4,5-
dihydroisoxazole [(1)-4a]
¨
Tetrahedron Lett. 1982, 23, 4777–4780. (c) Jager, V.; Schohe,
¨
¨
R. Tetrahedron 1984, 40, 2199–2210. (d) Jager, V.; Muller, I.
Tetrahedron 1985, 41, 3519–3528. (e) Curran, D. P.; Choi,
S.-M.; Gothe, S. A.; Lin, F.-T. J. Org. Chem. 1990, 55,
3710–3712. (f) Kanemasa, S.; Hayashi, T.; Yamamoto, H.;
Wada, E.; Sakurai, T. Bull. Chem. Soc. Jpn 1991, 64,
3274–3279. (g) Wallace, R. H.; Liu, J. Tetrahedron Lett.
1994, 35, 7493–7496. (h) Wallace, R. H.; Liu, J.; Zong, K. K.;
Crystal data. C16H25NO2Si, M¼291.46, monoclinic,
˚
a¼11.790(3), b¼24.800(4), c¼5.720(5) A, b¼91.798(3),
3
˚
V¼1672(1) A , space group P21/n, Z¼4. 4122 of reflections
were collected and 1851 unique reflections were used. Final

9620
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