Asymmetric epoxidation of cis-alkenes with arabinose-derived ketones: enantioselective synthesis of the side chain of Taxol

Article abstract of DOI:10.1016/j.tet.2006.01.116

The ee values of asymmetric epoxidation of cis-ethyl cinnamate 15 with arabinose-derived ketones as catalyst and Oxone as the terminal oxidant were found to increase inversely with the size of the catalyst acetal blocking group. Ketone catalyst

Full text of DOI:10.1016/j.tet.2006.01.116

Tetrahedron 62 (2006) 6621–6629
Asymmetric epoxidation of cis-alkenes with arabinose-derived
ketones: enantioselective synthesis of the side chain of TaxolÒ
*
Tony K. M. Shing, To Luk and Chi M. Lee
Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Received 18 November 2005; revised 30 December 2005; accepted 25 January 2006
Available online 26 May 2006
Abstract—The ee values of asymmetric epoxidation of cis-ethyl cinnamate 15 with arabinose-derived ketones as catalyst and OxoneÒ as the
terminal oxidant were found to increase inversely with the size of the catalyst acetal blocking group. Ketone catalyst 2, with the least bulky
methoxy acetal group, displayed the best enantioselectivity and afforded ethyl (2R,3R)-3-phenylglycidate 16 in 68% ee. Epoxide 16 was read-
ily converted into a protected side chain of TaxolÒ in five steps with an overall yield of 89%. The enantioselectivity of the epoxidation of other
cis-alkenes was moderate to poor.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
and the conversion of ethyl (2R,3R)-3-phenylglycidate into
a protected side chain of TaxolÒ.
Catalytic asymmetric epoxidation of alkenes is a versatile
synthetic method used to induce chirality into organic mole-
cules and the resultant epoxide moiety can be transformed
into a variety of target molecules.1 Great success has been
achieved in the epoxidation of allylic alcohols,2 trans- and
trisubstituted alkenes.3–11 For asymmetric epoxidation of
unfunctionalized cis-alkenes, Mn-salen catalyst is very
effective and practical.12 In recent years, chiral ketones13
and iminium salts,14 also have become promising reagents
for asymmetric epoxidation of unfunctionalized cis-alkenes.
2. Results and discussion
Dimethyl acetal 119,20 was readily accessible from L-arabi-
nose in two steps involving Fischer glycosidation21 and
trans-diol protection22 with 2,2,3,3-tetramethoxybutane in
76% overall yield. Oxidation of the free alcohol in 1 with
pyridinium dichromate (PDC) gave ketone 2 in 90% yield.
Ketones 8–12 were readily accessible from dimethyl acetal
1 via transacetalization23 and oxidation in good overall
yields (Scheme 1).19
Our long-term interest in the application of carbohydrates in
asymmetric synthesis has employed arabinose-derived alco-
hols as chiral auxiliaries in asymmetric Diels–Alder15 and
Hosomi–Sakurai reactions.16 Our efforts towards enantio-
selective epoxidation of alkenes have furnished chiral
ketone catalysts derived from D-glucose17 as well as 2-uloses
and 3-uloses derived from L-arabinose.18 We then have con-
centrated our research on arabinose because it is commer-
cially available in large quantities for both enantiomers.
Recently, we reported a series of arabinose-derived 4-ulo-
ses,19 containing a tunable steric blocker, which displayed
increasing enantioselectivity with the size of the acetal
alkoxy group in catalytic asymmetric epoxidation of trans-
disubstituted and trisubstituted alkenes. However, most
organocatalytic epoxidization of cis-alkenes proceeded with
moderate enantioselectivity.13,14 In this paper, we report
our study of the asymmetric epoxidation of cis-alkenes
with arabinose-derived ketones, using OxoneÒ as an oxidant
We also prepared a ketone catalyst 14, which had a dioxane
in place of the diacetal unit. Reduction of acetal 1 using
Et3SiH and BF3$Et2O24 in acetonitrile gave 1,4-dioxane 13
in 88% yield. Oxidation of the free alcohol in 13 with
PDC afforded ketone 14 in 92% yield (Scheme 2). In the
1H NMR spectrum, the coupling constant between the two
new protons in ketone 14 was 9.0 Hz, which showed that
they were diaxially disposed.
On the basis of our previous studies,17–19 the enantioselec-
tivity towards trans-disubstituted and trisubstituted alkenes
is sensitive to the size of the acetal steric blocker. For exam-
ple, ketone 10 with a more bulky neopentyl acetal group dis-
played better chiral induction than ketone 2, as the ee of
epoxidation of trans-stilbene was improved from 42% to
83%.19a Encouraged by these results, we went on to investi-
gate the chiral induction capabilities of these ketones in the
asymmetric epoxidation of cis-ethyl cinnamate, a starting
material for the synthesis of TaxolÒ side chain.25
Keywords: Asymmetric synthesis; Dioxirane; Epoxidation.
* Corresponding author. Tel.: +852 2609 6344; fax: +852 2603 5057;
e-mail: tonyshing@cuhk.edu.hk
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.116

6622
T. K. M. Shing et al. / Tetrahedron 62 (2006) 6621–6629
PDC
O
OBn
O
O
OBn
O
O
OBn
O
PDC
ROH
O
HO
HO
OR
OR
OMe
TsOH
O
RO
O
RO
O
MeO
1
2
R = methyl 90%
3
4
5
6
7
8
R = isobutyl 85%
R = isopentyl 80%
R = neopentyl 87%
R = benzyl 80%
R = isobutyl 95%
9
R = isopentyl 89%
R = neopentyl 96%
R = benzyl 84%
10
11
12
R = cyclohexylmethyl 76%
R = cyclohexylmethyl 92%
Scheme 1. Preparation of chiral ketone catalysts.
Table 1. Asymmetric epoxidation of cis-ethyl cinnamate using ketones
2, 8–12 and 14 as catalysts at 0 ꢀC
O
OBn
O
O
OBn
O
OBn
b
a
10 mol% catalyst
HO
O
H
O
H
O
HO
OMe
Oxone
O
O
MeO
O
H
O
H
°
C,
pH 7-7.5
0
Ph
CO2Et
Ph
CO2Et
1
13
14
15
16
Scheme 2. Reagents and conditions: (a) BF3$Et2O (3 equiv), Et3SiH
ꢀ
ꢀ
˚
(6 equiv), CH3CN, ꢁ20 C/0 C, 8 h, 88%; (b) PDC (1.5 equiv), 4 A
Catalysts:
O
MS, CH2Cl2, rt, 12 h, 92%.
2 R = methoxy
O
OBn
8
R = isobutoxy
Chemical synthesis of TaxolÒ side chain has drawn much at-
tention during the past decade.26–28 Asymmetric epoxidation
catalyzed by the readily available and low costing (salen)-
Mn(III) complex on cis-ethyl cinnamate 15 was reported
by Jacobsen.12d Since only trans-ethyl cinnamate is com-
mercially available, the desired cis-ethyl cinnamate 15 was
synthesized (Scheme 3).12d Partial reduction of ethyl phenyl
propiolate with Lindlar catalyst under H2 gave the desired
cis-ethyl cinnamate 15 in high yield (Scheme 3).29
9
R = isopentoxy
10 R = neopentoxy
11 R = benzyloxy
O
R
O
R
R = cyclohexylmethoxy
R = hydrogen
12
14
Entrya Catalysts Solvent
Yield (%)b ee (%)c Config.d
1
2
3
4
5
6
7
8
9
2
2
2
8
9
10
11
12
14
CH3CN
tBuOH
1,4-dioxane 95
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
93
85
68
37
61
56
44
36
63
49
67
(+)-(2R,3R)25
(+)-(2R,3R)25
(+)-(2R,3R)25
(+)-(2R,3R)25
(+)-(2R,3R)25
(+)-(2R,3R)25
(+)-(2R,3R)25
(+)-(2R,3R)25
(+)-(2R,3R)25
83
79
84
93
87
93
Ph
CO2Et
Ph
CO2Et
Ethyl phenyl
15
propiolate
a
All epoxidations were carried out with substrate (0.1 mmol), ketone
(0.01 mmol), OxoneÒ (1 mmol) and NaHCO3 (3.1 mmol) in CH3CN/
4ꢂ10-4 M aqueous EDTA (5:1, v/v) for 24 h.
Scheme 3. H2, Lindlar catalyst, n-hexane, 96%.
b
c
The epoxidation reactions were carried out at 0 ꢀC with
0.1 mmol of alkene and 10 mol % of catalyst in different sol-
vents at almost neutral conditions (pH 7–7.5). Table 1 shows
that acetonitrile (entry 1) was more suitable than tert-butanol
and 1,4-dioxane as a solvent (entries 2 and 3). In all cases,
the epoxides were isolated in high chemical yields (79–
95% yield), indicating that all the ketones are efficient cata-
lysts in terms of turnover. Ketones 2 and 14, with the least
bulky blocking groups, displayed the best chiral induction
(67–68% ee) (entries 1 and 9). Ketones with bulkier acetal
groups did not display better chiral induction with cis-alkene
15 as the ee decreased from 68% to 63% in the best case
(entries 1 and 7). When the R group changes to the very
bulky isopentoxy and neopentoxy groups (entries 5 and 6),
the ee drops to 44% and 36%, respectively. It is noteworthy
that ketone 10, with the most bulky neopentoxy group, gave
the poorest results (36% ee) whereas this ketone afforded the
best enantioselectivities with trans-disubstituted and trisub-
stituted alkenes.19a Anyway, ethyl (2R,3R)-3-phenylglycidate
Isolated yield.
Enantioselectivity was determined by 1H NMR analysis of the epoxide
products directly with shift reagent Eu(hfc)3.
d
The absolute configuration of the enantiomer in excess was determined by
comparing the sign of the optical rotation with the reported one.
16 was obtained in 68% ee using ketone 2 as the catalyst,
which is better than existing chiral ketone catalysts (Shi’s
44% ee13d and Seki’s 26% ee30). The Jacobson (salen)-
Mn(III) catalyst (95–97% ee) is still the best choice for this
epoxidation.12d
In our previous studies, we have presented a facile and
stereocontrolled synthetic avenue Òfor the construction of the
functionalized CD ring of Taxol .31 With ethyl (2R,3R)-
3-phenylglycidate 16 readily accessible, we now describe
a synthesis of a protected form of N-benzoyl-(2R,3S)-
phenylisoserine 17 (Fig. 1), TaxolÒ side chain.

T. K. M. Shing et al. / Tetrahedron 62 (2006) 6621–6629
6623
O
Ph
NH
O
17
2R
3S
Ph
OH
OH
Figure 1. N-benzoyl-(2R,3S)-phenylisoserine.
Asymmetric epoxidation catalyzed by catalyst 2 gave
epoxide 16 in 93% yield with 68% ee (Scheme 4). The op-
tical rotation of epoxide 16 was positive in sign, which is in
agreement with the literature data of the enantiomerically
enriched product.25 Mild acid catalyzed epoxide opening
at the benzylic position with NaN3 and NH4Cl gave azide
18, which was then benzoylated under standard conditions
to give benzoate 19 in 94% yield. The azide was readily re-
duced under hydrogenolysis conditions to give an amine.
Owing to the stability of an amide being greater than
that of an ester, the benzoyl group migrated to the amine
group in the presence of p-TsOH27b to give benzamide
20 in very good yield. To prevent the epimerization of
the hydroxyl group during further manipulation, protection
became necessary, which was accomplished by acetaliza-
tion using 2-methoxypropene in PPTS to give acetal 21
in 98% yield. The ee of 21 was determined to be 68%
Figure 2. X-ray structure of acid 22 (ORTEP view) (CCDC no. 185892).
liquor was 82% while that of the crystal counterpart was
only 5%.32
Crystals
5% ee
[α]D20
+1.1
(c 1.0, MeOH)
Ph
CO2H
1
recrystallization
using H NMR spectral analysis with chiral shift reagent,
BzN
O
Eu(hfc)3. Under basic conditions (LiOH, MeOH, H2O),
the ester 21 was saponified to give acid 22 in 93% yield
as a crystalline solid.
[α]D20
Mother liquor
82% ee
+70
(c 1.0, MeOH)
22
Scheme 5. Specific rotations of solid 22 and liquid 22.
At this point, the ee of acid 22 was at best 68%. Huge efforts
to increase the ee of 22 were made using recrystallization,
the excess amount of the desired (2R,3S)-enantiomer still
remained in the mother liquor. An X-ray crystallographic
analysis of a crystal confirmed the structure of acid 22
(Fig. 2).
The asymmetric epoxidation of other cis-alkenes was stud-
ied using ketones 2, 10, 11 and 14 as catalysts and the results
are shown in Table 2. In all cases, the epoxides were isolated
in high chemical yields (80–96% yield), indicating that all
the ketones are conversion-efficient. Ketones 14 and 2,
with the least bulky group, again consistently displayed
the best chiral induction (12–33% ee) (entries 1, 2, 5, 6, 9,
10, 13 and 14) among the ketones except for entry 9. Ketones
10 and 11 with the more bulky acetal group consistently
displayed poor results.
The specific rotations of the crystals and the concentrated
mother liquor were measured. As shown in Scheme 5, the
crystals gave almost no specific rotation, which hinted at a
racemic mixture. On the other hand, the specific rotation
of the mother liquor was +70 and the literature value27a for
the enantiomerically enriched acid was +99.1. Enantiomeric
excess measurement using chiral shift reagent was per-
formed to determine the relative amount of the enantiomers
in the mixture. The results showed that the ee of the mother
On the basis of the established spirol transition states6i,10h for
chiral dioxirane epoxidation and of our previous studies on
trans- disubstituted and trisubstituted alkenes,18,19 we found
N3
O
N3
O
O
a
c
b
Ph
OEt
Ph
OEt
Ph
CO2Et
Ph
CO2Et
OH
18
OBz
15
19
16 68% ee
Ph
BzN
CO2H
Ph
CO2Et
BzNH
Ph
O
d
e
f
OEt
O
BzN
O
OH
20
21
22
Scheme 4. Reagents and conditions: (a) catalyst 2 (0.1 equiv), OxoneÒ (9 equiv), NaHCO3 (29 equiv), CH3CN–EDTA (1:1, v/v), 93%; (b) NaN3 (2 equiv),
NH4Cl, EtOH, reflux, 92%; (c) Et3N (4 equiv), DMAP, BzCl (1.5 equiv), 94%; (d) H2, 10% Pd/C, p-TsOH, 98%; (e) 2-methoxypropene (10 equiv), PPTS,
toluene, reflux, 98%; (f) LiOH (2 equiv), MeOH, H2O, 93%.

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T. K. M. Shing et al. / Tetrahedron 62 (2006) 6621–6629
Table 2. Asymmetric epoxidation of cis-alkenes using ketones 2, 10, 11 and 14 as catalysts at 0 ꢀC
10 mol% catalyst
Oxone
O
CH3CN / H2O
R1
R2
R1
R2
°
0
C
pH 7-7.5
Catalysts:
O
O
OBn
O
OBn
O
O
O
OBn
O
O
OBn
O
O
O
O
O
O
OBn
OMe
H
O
O
O
BnO
O
H
MeO
14
11
2
10
Substrates:
OTr
TBSO
OTr
Ph
OTr
b
a
c
d
Entrya
Catalysts
Substrates
Yield (%)b
ee (%)c
Config.d
1
2
3
4
5
6
7
8
14
2
10
11
14
2
10
11
14
2
10
11
14
2
a
a
a
a
b
b
b
b
c
c
c
c
d
d
d
d
93
93
81
85
84
88
80
86
92
92
83
81
96
93
80
88
33
32
11
11
17
14
9
(ꢁ)-(1S,2R)33
(ꢁ)-(1S,2R)33
(ꢁ)-(1S,2R)33
(ꢁ)-(1S,2R)33
(+)e
(+)e
(+)e
3
(+)e
9
12
21
5
(+)e
10
11
12
13
14
15
16
(+)e
(+)e
6
(+)e
24
18
8
(+)e
(+)e
10
11
(+)e
8
(+)e
All epoxidations were carried out with substrate (0.1 mmol), ketone (0.01 mmol), OxoneÒ (1 mmol) and NaHCO3 (3.1 mmol) in CH3CN/4ꢂ10ꢁ4 M aqueous
a
EDTA (5:1, v/v) for 24 h.
b
c
d
e
Isolated yield.
Enantioselectivity was determined by 1H NMR analysis of the epoxide products directly with shift reagent Eu(hfc)3.
The absolute configuration of the enantiomer in excess was determined by comparing the sign of the optical rotation with the reported one.
The major absolute configurations were not determined.
that the enantioselectivity was sensitive and increased with
3. Experimental
the size of the acetal steric blocker.19 However, in the present
case with cis-alkenes, the ee increases inversely with the size
of the blocking groups. These evidences showed that the
transition state for epoxide formation of cis-alkenes may
be different with that of trans-alkenes. In order to rationalize
all the possible transition states and the corresponding
stereochemistry of the epoxides, more cis-alkene substrates
need to be investigated. This research is underway.
3.1. General
For general experimental section and procedure for ee deter-
mination, see Ref. 15a.
3.1.1. General epoxidation procedure at 0 ꢀC. To a stirred
solution of 1,2-dihydronaphthalene (0.1 mmol), ketone
(10 mol %) and n-Bu4NHSO4 (0.5 mg) in CH3CN (10 mL)
was added an aqueous buffer (5 mL, 4ꢂ10ꢁ4 M aqueous
EDTA). The resulting solution was cooled to 0 ꢀC (bath
temperature). A solution of OxoneÒ (307 mg, 0.5 mmol)
in aqueous EDTA (5 mL, 4ꢂ10ꢁ4 M) and a solution of
NaHCO3 (252 mg, 3.0 mmol) in H2O (5 mL) were added
dropwise concomitantly via two dropping funnels. The pH
of the mixture was maintained at about 7–7.5 over a period
of 24 h. The reaction mixture was then poured into water
In conclusion, the ee of the asymmetric epoxidation of cis-
alkenes decreased with the size of the acetal blocking groups
using arabinose-derived ketones. Ketone catalyst 2 with
the least bulky acetal group displayed the best enantioselec-
tivity and afforded ethyl (2R,3R)-3-phenylglycidate 16 in
69% ee. Epoxide 16 was converted into acid 22, the pro-
tected side chain of TaxolÒ, in five steps with an overall yield
of 89%.

T. K. M. Shing et al. / Tetrahedron 62 (2006) 6621–6629
6625
(10 mL), extracted with Et2O (3ꢂ), dried with anhydrous
magnesium sulfate, and filtered. The filtrate was concen-
trated under reduced pressure to give a residue that was
purified by flash column chromatography to give the epoxide.
reaction mixture was then poured into water (10 mL), ex-
tracted with Et2O (3ꢂ), dried with anhydrous magnesium
sulfate and filtered. The filtrate was concentrated under
reduced pressure to give a residue that was purified by flash
column chromatography to give the epoxide 16 as a colour-
less syrup (32 mg, 93%): Rf 0.40 (hexane–Et2O, 5:1); The ee
3.1.2. Alcohol 13. To a solution of dimethyl acetal 1
(160 mg, 0.45 mmol) in dry CH3CN (8 mL) at ꢁ20 ꢀC
was added slowly BF3$Et2O (0.17 mL, 1.35 mmol). The
mixture was stirred for 1 h and Et3SiH (0.43 mL,
2.71 mmol) was added at ꢁ20 ꢀC. The temperature of the
resulting mixture was raised to 0 ꢀC and stirred for another
8 h. The cooled reaction mixture was then treated with satu-
rated aqueous NaHCO3 and extracted with EtOAc
(3ꢂ20 mL). The combined organic extracts were dried
over anhydrous MgSO4 and filtered. The filtrate was concen-
trated under reduced pressure. The crude residue was puri-
fied by flash column chromatography to give alcohol 13 as
a pale yellow syrup (117 mg, 88%): Rf 0.30 (hexane–EtOAc,
1:1); [a]2D0 +140.03 (c 1.64, CHCl3); IR (thin film) 3473
1
of the epoxide was determined to be 68% by H NMR
analysis with chiral shift reagent, Eu(hfc)3. Data for epoxide
16: [a]2D0 +33.9 (c 0.32, CHCl3); IR (thin film) 1740, 1697,
1
1649, 1542 cmꢁ1; H NMR (CDCl3) d 7.42 (2H, m), 7.33
(3H, m), 4.27 (1H, d, J¼4.5 Hz), 3.99 (2H, m), 3.82 (1H,
d, J¼4.5 Hz), 1.01 (3H, t, J¼7.2 Hz); 13C NMR (CDCl3)
d 166.6, 132.8, 128.4, 127.9, 126.6, 61.2, 57.4, 55.7, 13.8;
MS (CI) m/z (relative intensity) 193 ([M+H]+, 100), 165
(20), 119 (40), 91 (42); HRMS (CI) calcd for C11H13O3
[M+H]+ 193.0895, found 193.0861.
3.1.5. Azide 18. Sodium azide (14 mg, 0.208 mmol) and
NH4Cl (2.5 mg, 14 mmol) were added to a stirred solution
of epoxide 16 (20 mg, 0.104 mmol) in 80% aqueous EtOH
(3 mL) at room temperature. The reaction mixture was
refluxed for 24 h and quenched with saturated NaHCO3.
The aqueous phase was extracted with Et2O (3ꢂ) and the
combined organic layers were dried over anhydrous MgSO4
and filtered. The filtrate was concentrated under reduced
pressure. The crude residue was purified by flash column
chromatography to afford azide 18 as a colourless oil
(22 mg, 92%): Rf 0.25 (hexane–Et2O, 2:1); IR (thin film)
1
(OH) cmꢁ1; H NMR (CDCl3) d 7.31–7.17 (5H, m), 4.91
(1H, d, J¼1.8 Hz), 4.70 (1H, d, J¼12.6 Hz), 4.56 (1H, d,
J¼12.3 Hz), 3.89 (1H, d, J¼1.5 Hz), 3.80 (2H, m), 3.75
(1H, d, J¼1.5 Hz), 3.66 (1H, dd, J¼12.6, 1.8 Hz), 3.48
(1H, dq, J¼8.7, 6.2 Hz), 3.32 (1H, dq, J¼9.0, 6.3 Hz),
2.08 (1H, br s), 1.09 (3H, d, J¼6.3 Hz), 1.06 (3H, d,
J¼6.0 Hz); 13C NMR (acetone) d 139.5, 129.3, 128.7,
128.5, 98.4, 78.4, 78.3, 74.4, 74.0, 69.9, 68.9, 64.8, 18.0,
17.9; MS (EI) m/z (relative intensity) 294 ([M]+, 100), 295
(15); HRMS (EI) calcd for C16H22O5 [M]+ 294.1462, found
294.1461; Anal. Calcd for C16H22O5: C, 65.29; H, 7.53.
Found: C, 64.94; H, 7.69.
3462, 2359, 2107, 1736, 1266, 1112 cmꢁ1 1H NMR
;
(CDCl3) d 7.42 (5H, m), 4.85 (1H, d, J¼3.0 Hz), 4.37 (1H,
dd, J¼6.9, 3.0 Hz), 4.29 (2H, q, J¼7.2 Hz), 3.13 (1H, d,
J¼6.6 Hz), 1.30 (3H, t, J¼7.2 Hz); 13C NMR (CDCl3)
d 171.9, 128.8, 128.7, 128.6, 127.8, 73.9, 67.1, 62.4, 14.1;
MS (CI) m/z (relative intensity) 236 ([M+H]+, 5), 208
(100), 193 ([MꢁN3]+, 76); HRMS (CI) calcd for
C11H14N3O3 [M+H]+ 236.1030, found 236.1031.
3.1.3. Ketone 14. To a solution of alcohol 13 (170 mg,
0.57 mmol) in dry CH2Cl2 (10 mL) were added slowly
˚
PDC (261 mg, 0.69 mmol) and powdered 4 A molecular
sieves (260 mg). The mixturewas stirred at room temperature
for 12 h. The mixture was suction filtered through a pad of
silica gel and the filtrate was concentrated under reduced
pressure. The crude residue was purified by flash column
chromatography to afford ketone 14 as a colourless syrup
(154 mg, 92%): Rf 0.22 (hexane–EtOAc, 1:1); [a]D20
3.1.6. Benzoate 19. Et3N (1.7 mL, 11.9 mmol) and benzoyl
chloride (0.56 mL, 4.8 mmol) were added to a stirring solu-
tion of azide 18 (700 mg, 2.98 mmol) and DMAP (5 mg) in
dry CH2Cl2 (20 mL) under N2. The reaction mixture was
stirred for 30 min and quenched with saturated NH4Cl.
The mixture was extracted with Et2O (3ꢂ) and the combined
organic layers were dried over anhydrous MgSO4 and fil-
tered. The filtrate was concentrated under reduced pressure.
The crude residue was purified by flash column chromato-
graphy to give benzoate 19 as a colourless oil (950 mg,
94%): Rf 0.58 (hexane–Et2O, 2:1); IR (thin film) 3328,
+136.43 (c 5.98, CHCl3); IR (thin film) 1742 (C]O) cmꢁ1
;
1H NMR (CDCl3) d 7.37–7.26 (5H, m), 5.08 (1H, d, J¼
3.3 Hz), 4.79 (1H, d, J¼12.3 Hz), 4.70 (1H, d, J¼12.3 Hz),
4.59 (1H, d, J¼10.2 Hz), 4.15 (1H, d, J¼14.7 Hz), 3.86
(1H, d, J¼14.7 Hz), 3.74 (1H, dd, J¼10.4, 3.3 Hz), 3.45
(1H, dq, J¼9.0, 6.3 Hz), 3.34 (1H, dq, J¼8.7, 6.3 Hz), 1.17
(3H, d, J¼6.3 Hz), 1.14 (3H, d, J¼6.0 Hz); 13C NMR
(CDCl3) d 199.3, 136.5, 128.1, 127.6, 127.3, 96.0, 77.3,
77.2, 76.9, 76.4, 69.7, 66.3, 16.7, 16.4; MS (EI) m/z (relative
intensity) 292 ([M]+, 100), 290 (35); HRMS (EI) calcd for
C16H20O5 [M]+ 292.1305, found 292.1303.
1
2106, 2107, 1729, 1250, 1110, 1020, 707 cmꢁ1; H NMR
(CDCl3) d 8.13 (2H, m), 7.38 (8H, m), 5.45 (1H, d,
J¼5.1 Hz), 5.15 (1H, d, J¼5.1 Hz), 4.15 (2H, dq, J¼7.2,
0.9 Hz), 1.14 (3H, t, J¼7.2 Hz); 13C NMR (CDCl3)
d 167.2, 165.5, 134.5, 133.6, 130.5, 129.9, 129.0, 128.7,
128.5, 127.8, 127.5, 126.4, 75.5, 65.5, 61.9, 13.8; MS (CI)
m/z (relative intensity) 340 ([M+H]+, 22), 298 ([MꢁN3]+,
100), 266 (100); HRMS (CI) calcd for C18H18N3O4
[M+H]+ 340.1292, found 340.1294.
3.1.4. Epoxide 16. To a stirred solution of cis-ethyl cinna-
mate (32 mg, 0.18 mmol), ketone 2 (7 mg, 10 mol %) and
n-Bu4NHSO4 (0.5 mg) in CH3CN (10 mL) was added an
aqueous buffer (5 mL, 4ꢂ10ꢁ4 M aqueous EDTA). The
resulting solution was cooled to 0 ꢀC (bath temperature).
A solution of OxoneÒ (550 mg, 0.9 mmol) in aqueous EDTA
(5 mL, 4ꢂ10ꢁ4 M) and a solution of NaHCO3 (453 mg,
5.2 mmol) in H2O (5 mL) were added dropwise concomi-
tantly via two dropping funnels. The pH of the mixture
was maintained at about 7–7.5 over a period of 24 h. The
3.1.7. Benzamide 20. A suspension of 10% palladium on
charcoal (100 mg, excess) in EtOAc (10 mL) was degassed
and refilled with hydrogen gas three times and then stirred
for 10 min. A solution of benzoate 19 (960 mg, 2.83 mmol)
and p-TsOH (10 mg) in EtOAc (10 mL) was added. The

6626
T. K. M. Shing et al. / Tetrahedron 62 (2006) 6621–6629
reaction mixture was stirred for 24 h under H2, quenched
with Et3N, and filtered with filter paper. The solvents of the
filtrate were removed under reduced pressure and the residue
was purified by flash chromatography to afford benzamide 20
as a white solid (868 mg, 98%): mp 143–144 ꢀC; Rf 0.38
(hexane–EtOAc, 2:1); IR (thin film) 3431, 3349, 1718,
128.5, 128.0, 127.7, 126.8, 126.1, 97.9, 81.1, 65.4, 26.1,
25.4; MS (EI) m/z (relative intensity) 325 ([M]+, 15), 310
([MꢁCH3]+, 87), 105 (100); HRMS (EI) calcd for
C19H19NO4 [M]+ 325.1309, found 325.1304.
Data for the mother liquor: [a]2D0 +70.3 (c 0.6, MeOH) (lit.27a
for enantiomerically enriched acid, [a]2D0 +99.1 (c 0.36,
EtOH)). The acid 22 is not sensitive to chiral shift reagent
Eu(hfc)3 under various solvents and concentrations. To over-
come this, the mother liquor from recrystallization was
esterified to convert 22 back to ester 21, which displayed
better resolution of the separated signals in the 1H NMR spec-
trum upon Eu(hfc)3 addition. DBU (13 mL, 0.09 mmol) and
ethyl bromide (7 mL, 0.09 mmol) were added to a stirred
solution of the liquid acid 22 (15 mg, 0.046 mmol) in dry
benzene (2 mL). The reaction mixture was stirred at reflux
for 1 h and quenched with saturated NH4Cl. The aqueous
phase was extracted with Et2O (3ꢂ). The combined organic
layers were dried over anhydrous MgSO4 and filtered. The
filtrate was concentrated under reduced pressure. The crude
residue was purified by flash column chromatography to
afford ester 21 as a colourless oil (15 mg, 92%). The ee of
ester 21 was measured to be 82% by the same method
described above.
1
1637, 1535, 1095 cmꢁ1; H NMR (CDCl3) d 7.76 (2H, d,
J¼6.9 Hz), 7.45 (8H, m), 6.99 (1H, d, J¼9.0 Hz), 5.76 (1H,
dd, J¼9.3, 2.1 Hz), 4.63 (1H, d, J¼2.1 Hz), 4.28 (2H, m),
3.31 (1H, br s), 1.31 (3H, t, J¼7.2 Hz); 13C NMR (CDCl3)
d 172.9, 166.8, 138.7, 134.1, 131.7, 128.6, 128.5, 127.8,
127.6, 127.0, 126.9, 73.3, 62.6, 54.8, 14.1; MS (CI) m/z (rela-
tive intensity) 314 ([M+H]+, 45), 297 ([MꢁOH]+, 17), 208
(84), 193 (100); HRMS (CI) calcd for C18H20NO4 [M+H]+
314.1387, found 314.1383.
3.1.8. Acetal 21. 2-Methoxypropene (0.31 mL, 3.19 mmol)
was added to a stirred solution of benzamide 20 (100 mg,
0.319 mmol) in dry toluene (7 mL) under N2. Pyridinium
p-toluenesulfonate (PPTS) (3 mg) was added to the mixture,
which was refluxed for 20 h under N2. The reaction mixture
was quenched with aqueous NaHCO3 and the aqueous phase
was extracted with Et2O (3ꢂ). The combined organic layers
were dried over anhydrous MgSO4 and filtered. The filtrate
was concentrated under reduced pressure. The crude residue
was purified by flash column chromatography to give acetal
21 as a colourless oil (110 mg, 98%): Rf 0.38 (hexane–
EtOAc, 1:1); IR (thin film) 3368, 1736, 1645, 1528, 1275,
In the same manner, the ee of the ester prepared from crys-
talline acid 22 was determined to be 5%.
1
1112, 704 cmꢁ1; H NMR (CDCl3) d 7.14 (9H, m), 6.93
3.2. Preparation of alkene substrates
(1H, br s), 5.24 (1H, d, J¼5.7 Hz), 4.55 (1H, d, J¼6.0 Hz),
4.25 (2H, m), 1.96 (3H, s), 1.87 (3H, s), 1.27 (3H, t,
J¼7.2 Hz); 13C NMR (CDCl3) d 169.4, 169.1, 138.9,
137.6, 129.3, 128.4, 128.0, 127.7, 126.8, 126.1, 97.8, 81.2,
65.4, 61.9, 26.0, 25.6, 14.1; MS (EI) m/z (relative intensity)
353 ([M]+, 17), 338 ([MꢁCH3]+, 99), 295 (100); HRMS (EI)
calcd for C21H23NO4 [M]+ 353.1622, found 353.1632. The
ee was determined to be 68% by 1H NMR spectral analysis
upon chiral shift reagent addition.
3.2.1.
cis-Ethyl cinnamate.29 To a stirred mix-
Ph
CO Et
2
ture of ethyl phenyl propiolate (1 g, 5.74 mmol), n-hexane
(25 mL) and 1-octene (6 mL) was added quinoline (1.03 g,
8 mmol). Palladium on calcium carbonate (Lindlar catalyst
290 mg, 1.7 mmol) was added and the resulting reaction
mixture was stirred under H2 with a hydrogen balloon at
room temperature for 20 h. The resulting mixture was fil-
tered through filter paper. The filtrate was concentrated un-
der reduced pressure. The crude residue was purified by
flash column chromatography to afford cis-ethyl cinnamate
as a colourless oil (960 mg, 96%): Rf 0.78 (hexane–Et2O,
3.1.9. Acid 22. Lithium hydroxide (120 mL, 3.96 mmol)
was added to a stirred solution of ester 21 (700 mg,
1.98 mmol) in 70% aqueous MeOH (9 mL) at room tempera-
ture. The reaction mixture was stirred for 24 h at room tem-
perature. The solvent was removed in vacuo and H2O
(3 mL) was added to the residue. Saturated NH4Cl (3 mL)
was added to the mixture until the pH reached 4. The aqueous
1
5:1); H NMR (CDCl3) d 7.58 (2H, m), 7.35 (3H, m), 6.95
(1H, d, J¼12.6 Hz), 5.95 (1H, d, J¼12.6 Hz), 4.18 (2H, q,
J¼7.2 Hz), 1.25 (3H, t, J¼7.2 Hz); 13C NMR (CDCl3)
d 142.9, 129.6, 128.9, 127.9, 119.9, 60.3, 14.1.
phase was extracted with CH2Cl2 (3ꢂ). The combined
organic layers were dried over anhydrous MgSO4 and fil-
tered. The filtrate was concentrated under reduced pressure.
The crude residue was purified by flash column chromato-
graphy to afford acid 22 as a white solid (600 mg, 93%). A
single crystal suitable for X-ray crystallographic analysis
was obtained in MeOH. The optical rotations of the crystals
and the mother liquor obtained from recrystallization were
different as indicated below.
3.2.2.
OTr cis-1-Trityloxy-3-hexene. Trityl chlo-
ride (2.46 g, 8.86 mmol) and DMAP (7 mg) were added to
a stirring mixture of cis-3-hexen-1-ol (807 mg, 8.05 mmol)
and pyridine (0.98 mL, 12.1 mmol) in dry CH2Cl2 (20 mL).
The reaction mixture was stirred for 24 h. The reaction was
with saturated aqueous NH4Cl and extracted with Et2O
(3ꢂ30 mL). The combined organic extracts were dried over
anhydrous MgSO4 and filtered. The filtrate was concentrated
under reduced pressure. The crude residue was purified by
flash column chromatography to afford cis-1-trityloxy-3-
hexene as a colourless oil (2.79 g, 92%): Rf 0.33 (hexane–
Data for crystals: mp 175–176 ꢀC (lit.27a for enantiomeri-
cally enriched acid, mp 213 ꢀC); [a]D20 +1.1 (c 0.7,
MeOH); Rf 0.32 (CHCl3–MeOH, 4:1); IR (thin film) 3449,
1
Et2O, 30:1); H NMR (CDCl3) d 7.48–7.23 (15H, m), 5.48
2933, 1740, 1639, 1390, 1250, 1209 cmꢁ1
;
1H NMR
(1H, m), 5.39 (1H, m), 3.11 (2H, t, J¼6.9 Hz), 2.41(1H, d, J¼
6.9 Hz), 2.34(1H, d, J¼6.9 Hz),2.12(1H, dq, J¼7.5, 7.2 Hz),
0.99 (3H, t, J¼7.5 Hz); 13C NMR (CDCl3) d 144.7, 133.8,
129.0, 128.0, 127.2, 125.7, 86.8, 63.9, 28.5, 21.0, 14.7.
(CD3OD) d 7.18 (8H, m), 6.95 (2H, br s), 5.26 (1H, d,
J¼5.7 Hz), 4.57 (1H, d, J¼5.7 Hz), 1.92 (3H, s), 1.84 (3H,
s); 13C NMR (CDCl3) d 172.8, 169.5, 138.8, 137.2, 129.5,

T. K. M. Shing et al. / Tetrahedron 62 (2006) 6621–6629
n
6627
3.2.3.
1-Trityloxy-4-phenyl-2-butyne. BuLi
3.2.7.
(Z)-1-Trityloxy-4-tert-butyldi-
OTr
OTr
TBSO
Ph
(1.6 M, 12.5 mL, 19.0 mmol) was added to a solution of
the 1-trityloxy-2-propyne34 (2.97 g, 9.96 mmol) in dry
THF at 0 ꢀC. The mixture was stirred at room temperature.
After 1 h, BnBr was added to the reaction mixture. BnBr
(2.37 mL, 19.0 mmol) was added to the mixture and the re-
sulting solution was stirred for 24 h. The reaction was
with saturated aqueous NH4Cl and extracted with Et2O
(3ꢂ30 mL). The combined organic extracts were dried over
anhydrous MgSO4 and filtered. The filtrate was concentrated
under reduced pressure. The crude residue was purified by
flash column chromatography to afford 1-trityloxy-4-phenyl-
2-butyne as a yellow oil (3.21 g, 79%): Rf 0.44 (hexane–
methylsilyloxy-2-butene. Trityl chloride (3.44 g, 15.7 mmol)
and DMAP (8 mg) were added to a stirring mixture of
(Z)-1-tert-butyldimethylsilyloxy-2-buten-4-ol35 (2.50 mg,
12.3 mmol) and pyridine (1.0 mL, 15.7 mmol) in dry CH2Cl2
(40 mL). Thereactionmixturewasstirredfor24 h. Thereaction
was with saturated aqueous NH4Cl and extracted with Et2O
(3ꢂ40 mL). The combined organic extracts were dried over
anhydrous MgSO4 and filtered. The filtrate was concentrated
under reduced pressure. The crude residue was purified by flash
column chromatography to afford (Z)-1-trityloxy-4-tert-butyl-
dimethylsilyloxy-2-butene as a colourless oil (5.10 g, 93%):
1
Rf 0.33 (hexane–Et2O, 20:1); H NMR (CDCl3) d 7.51–7.26
1
Et2O, 10:1); H NMR (CDCl3) d 7.59–7.29 (20H, m), 3.91
(15H, m), 5.75–5.65 (2H, m), 4.12 (2H, d, J¼5.7 Hz), 3.71
(2H, d, J¼5.4 Hz), 0.90 (9H, s), 0.04 (6H, s); 13C NMR
(CDCl3) d 144.4, 132.1, 129.0, 128.2, 127.5, 127.3, 87.2,
60.7, 60.1, 26.3, 18.6, ꢁ4.82.
(2H, t, J¼2.1 Hz), 3.71 (2H, s); 13C NMR (CDCl3)
d 143.9, 136.9, 128.9, 128.8, 128.2, 128.1, 127.7, 127.4,
126.9, 87.7, 83.7, 79.2, 53.9, 25.6; MS (EI) m/z (relative
intensity) 388 ([M]+, 100), 243 (98), 211 (100); HRMS
(EI) calcd for C29H24O1 [M]+ 388.1822, found 388.1816.
O
3.2.8.
methylsilyloxy-2,3-epoxybutane. Colourless oil: Rf 0.34
(hexane–Et2O, 10:1); H NMR (CDCl3) d 7.53–7.26 (15H,
m), 3.72 (1H, dd, J¼12.0, 6.0 Hz), 3.55 (1H, dd, J¼12.0,
4.2 Hz), 3.37–3.29 (2H, m), 3.21–3.16 (2H, m), 0.91 (9H,
s), 0.04 (3H, s), 0.03 (3H, s); 13C NMR (CDCl3) d 144.1,
128.9, 128.2, 127.4, 87.2, 62.7, 62.1, 56.8, 55.4, 26.2,
18.6, ꢁ4.88, ꢁ5.05; MS (CI) m/z (relative intensity) 461
([MH]+, 10), 444 (45), 443 (100); HRMS (CI) calcd for
C29H36O3Si1 [MH]+ 461.2508, found 461.2503.
1-Trityloxy-4-tert-butyldi-
OTr
TBSO
Ph
OTr
cis-1-Trityloxy-4-phenyl-2-butene.
3.2.4.
1
To a stirred mixture of 1-trityloxy-4-phenyl-2-butyne
(200 mg, 0.49 mmol), n-hexane (12 mL) and 1-octene
(3 mL) was added quinoline (98 mg, 0.76 mmol). Palladium
on calcium carbonate (Lindlar catalyst 30 mg, 0.25 mmol)
was added and the resulting reaction mixture was stirred
under H2 with a hydrogen balloon at room temperature for
20 h. The resulting mixture was filtered through filter paper.
The filtrate was concentrated under reduced pressure. The
crude residue was purified by flash column chromatography
to afford cis-1-trityloxy-4-phenyl-2-butene as a pale yellow
Acknowledgements
1
oil (181 mg, 90%): Rf 0.50 (hexane–Et2O, 10:1); H NMR
(CDCl3) d 7.53–7.26 (20H, m), 5.86 (1H, m), 5.82 (1H,
m), 3.80 (2H, d, J¼6.3 Hz), 3.27 (2H, d, J¼7.2 Hz); 13C
NMR (CDCl3) d 144.5, 131.1, 129.0, 128.8, 128.7, 128.2,
127.9, 127.7, 127.3, 126.3, 87.2, 60.6, 34.3; MS (ESI) m/z
(relative intensity) 413 ([M+Na]+, 100), 414 (30); HRMS
(ESI) calcd for C29H26O1 [M+Na]+ 413.1876, found
413.1882.
This research was supported by a CUHK Direct Grant.
References and notes
1. Xia, Q. H.; Ge, H. Q.; Ye, C. P.; Liu, Z. M.; Su, K. X. Chem.
Rev. 2005, 105, 1603.
2. (a) Katsuki, T.; Martin, V. S. Org. React. 1996, 48, 1; (b)
Johnson, R. A.; Sharpless, K. B. Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH: New York, NY, 1993,
Chapter 4.1; (c) Rossiter, B. E.; Katsuki, T.; Sharpless, K. B.
J. Am. Chem. Soc. 1981, 103, 464; (d) Katsuki, T.; Sharpless,
K. B. J. Am. Chem. Soc. 1980, 102, 5974.
3. For reviews, see: (a) Yang, D. Acc. Chem. Res. 2004, 37, 497;
(b) Shi, Y. Acc. Chem. Res. 2004, 37, 488; (c) Frohn, M.; Shi, Y.
Synthesis 2000, 14, 1979.
4. (a) Matsumoto, K.; Tomioka, K. Tetrahedron Lett. 2002, 43,
631; (b) Klein, S.; Roberts, S. M. J. Chem. Soc., Perkin
Trans. 1 2002, 2686; (c) Stearman, C. J.; Behar, V.
Tetrahedron Lett. 2002, 43, 1943; (d) Seki, M.; Furutani, T.;
Hatsuda, M.; Imashiro, R. Tetrahedron Lett. 2000, 41, 2149;
(e) Carnell, A. J.; Johnstone, R. A. W.; Parsy, C. C.;
Sanderson, W. R. Tetrahedron Lett. 1999, 40, 8029; (f)
Dakin, L. A.; Panek, J. S. Chemtracts 1998, 11, 531; (g)
Bergbreiter, D. E. Chemtracts 1997, 10, 661; (h) Song, C. E.;
Kim, Y. H.; Lee, K. C.; Lee, S. G.; Jin, B. W. Tetrahedron:
Asymmetry 1997, 8, 2921.
O
3.2.5.
1-Trityloxy-4-phenyl-2,3-epoxy-
OTr
Ph
1
butane. Colourless oil: Rf 0.25 (hexane–Et2O, 10:1); H
NMR (CDCl3) d 7.53–7.26 (20H, m), 3.55 (1H, dd,
J¼10.2, 5.4 Hz), 3.33 (1H, dd, J¼5.4, 4.2 Hz), 3.24 (2H,
m), 2.78 (1H, dd, J¼15.0, 6.0 Hz), 2.66 (1H, dd, J¼15.0,
6.3 Hz); 13C NMR (CDCl3) d 144.1, 137.8, 129.2, 129.0,
128.9, 128.2, 127.5, 126.9, 87.3, 62.4, 57.1, 55.7, 34.6;
MS (CI) m/z (relative intensity) 389 (100), 390 (30), 407
([MH]+, 10); HRMS (CI) calcd for C29H26O2 [MH]+
407.2006, found 407.1995.
O
OTr
3.2.6.
1-Trityloxy-3,4-epoxyhexane. Col-
ourless oil: Rf 0.23 (hexane–Et2O, 10:1); 1H NMR
(CDCl3) d 7.47–7.21 (15H, m), 3.28 (1H, t, J¼6.3 Hz),
3.15 (1H, q, J¼5.1 Hz), 2.93 (1H, q, J¼5.1 Hz), 1.85 (2H,
m), 1.54 (2H, dt, J¼14.1, 6.9 Hz), 1.04 (3H, t, J¼7.5 Hz);
13C NMR (CDCl3) d 144.5, 129.0, 128.1, 127.3, 87.0,
61.5, 58.6, 55.4, 29.0, 21.5, 11.0; MS (CI) m/z (relative
intensity) 358 ([M]+, 30), 341 (100); HRMS (CI) calcd for
C25H26O2 [M]+ 358.1927, found 358.1918.
5. (a) Curci, R.; D’Accolti, L.; Fiorentino, M.; Rosa, A.
Tetrahedron Lett. 1995, 36, 5831; (b) Curci, R.; Fiorentino,
M.; Serio, M. R. J. Chem. Soc., Chem. Commun. 1984, 155.

6628
T. K. M. Shing et al. / Tetrahedron 62 (2006) 6621–6629
6. (a) Yang, D.; Jiao, G.-S.; Yip, Y.-C.; Lai, T.-H.; Wong, M.-K.
J. Org. Chem. 2001, 66, 4619; (b) Yang, D.; Jiao, G.-S.
Chem.—Eur. J. 2000, 6, 3517; (c) Yang, D.; Jiao, G.-S.; Yip,
Y.-C.; Wong, M.-K. J. Org. Chem. 1999, 64, 1635; (d) Yang,
D.; Wong, M.-K.; Yip, Y.-C.; Wang, X.-C.; Tang, M.-W.;
Zheng, J.-H.; Cheung, K.-K. J. Am. Chem. Soc. 1998, 120,
5943; (e) Yang, D.; Yip, Y.-C.; Chen, J.; Cheung, K.-K.
J. Am. Chem. Soc. 1998, 120, 7659; (f) Yang, D.; Yip, Y.-C.;
Tang, M.-W.; Wong, M.-K.; Cheung, K.-K. J. Org. Chem.
1998, 63, 9888; (g) Yang, D.; Yip, Y.-C.; Jiao, G.-S.; Wong,
M.-K. J. Org. Chem. 1998, 63, 8952; (h) Yang, D.; Yip, Y.-C.;
Tang, M.-W.; Wong, M.-K.; Zheng, J.-H.; Cheung, K.-K.
J. Am. Chem. Soc. 1996, 118, 491; (i) Yang, D.; Wang, X.-C.;
Wong, M.-K.; Yip, Y.-C.; Tang, M.-W. J. Am. Chem. Soc.
1996, 118, 11311.
L. J. Am. Chem. Soc. 1991, 113, 7063; (f) Lee, N. H.; Muci,
A. R.; Jacobsen, E. N. Tetrahedron Lett. 1991, 32, 5055.
13. (a) Shu, L.; Shi, Y. Tetrahedron Lett. 2004, 45, 8115; (b) Shu,
L.; Wang, P.; Gan, Y.; Shi, Y. Org. Lett. 2003, 5, 293; (c) Tian,
H.; She, X.; Yu, H.; Shu, L.; Shi, Y. J. Org. Chem. 2002, 67,
2435; (d) Tian, H.; She, X.; Shu, L.; Yu, H.; Shi, Y. J. Am.
Chem. Soc. 2000, 122, 11551.
14. (a) Page, P. C. B.; Buckley, B. R.; Heaney, H.; Blacker, A. J.
Org. Lett. 2005, 7, 375; (b) Page, P. C. B.; Buckley, B. R.;
Blacker, A. J. Org. Lett. 2004, 6, 1543.
15. (a) Shing, T. K. M.; Chow, H.-F.; Chung, I. H. F. Tetrahedron
Lett. 1996, 37, 3713; (b) Shing, T. K. M.; Lloyd-Williams, P.
J. Chem. Soc., Chem. Commun. 1987, 423.
16. Shing, T. K. M.; Li, L.-H. J. Org. Chem. 1997, 62, 1230.
17. Shing, T. K. M.; Leung, G. Y. C. Tetrahedron 2002, 58,
7545.
7. (a) Adam, W.; Saha-Moller, C. R.; Zhao, C.-G. Tetrahedron:
¨
Asymmetry 1999, 10, 2749; (b) Adam, W.; Zhao, C.-G.
Tetrahedron: Asymmetry 1997, 8, 3995.
18. Shing, T. K. M.; Leung, Y. C.; Yeung, K. W. Tetrahedron 2003,
59, 2159.
8. (a) Armstrong, A.; Ahmed, G.; Dominguez-Fernandez, B.;
Hayter, B. R.; Wailes, J. S. J. Org. Chem. 2002, 67, 8610; (b)
Armstrong, A.; Moss, W. O.; Reeves, J. R. Tetrahedron:
Asymmetry 2001, 12, 2779; (c) Armstrong, A.; Hayter, B. R.;
Moss, W. O.; Reeves, J. R.; Wailes, J. S. Tetrahedron: Asymme-
try 2000, 11, 2057; (d) Armstrong, A. Chem. Commun. 1998,
621.
9. (a) Denmark, S. E.; Wu, Z.; Crudden, C. M.; Matsuhashi, H.
J. Org. Chem. 1997, 62, 8288; (b) Denmark, S. E.; Forbes,
D. C.; Hays, D. S.; DePue, J. S.; Wilde, R. G. J. Org. Chem.
1995, 60, 1391.
10. (a) Lorenz, J. C.; Frohn, M.; Zhou, X. M.; Zhang, J. R.; Tang,
Y.; Burke, C.; Shi, Y. J. Org. Chem. 2005, 70, 2904; (b) Shu, L.;
Shen, Y.-M.; Burke, C.; Goeddel, D.; Shi, Y. J. Org. Chem.
2003, 68, 4963; (c) Wu, X.-Y.; She, X.; Shi, Y. J. Am. Chem.
Soc. 2002, 124, 8792; (d) Tian, H.; She, X.; Xu, J.; Shi, Y.
Org. Lett. 2001, 3, 1929; (e) Tian, H.; She, X.; Shi, Y. Org.
Lett. 2001, 3, 715; (f) Wang, Z.-X.; Miller, S. M.; Anderson,
O. P.; Shi, Y. J. Org. Chem. 2001, 66, 521; (g) Shu, L.; Shi,
Y. Tetrahedron 2001, 57, 5213; (h) Warren, J. D.; Shi, Y.
J. Org. Chem. 1999, 64, 7675; (i) Wang, Z.-X.; Cao, G.-A.;
Shi, Y. J. Org. Chem. 1999, 64, 7646; (j) Wang, Z.-X.;
Miller, S. M.; Anderson, O. P.; Shi, Y. J. Org. Chem. 1999,
64, 6443; (k) Frohn, M.; Dalkiewicz, M.; Tu, Y.; Wang,
Z.-X.; Shi, Y. J. Org. Chem. 1998, 63, 2948; (l) Cao, G.-A.;
Wang, Z.-X.; Tu, Y.; Shi, Y. Tetrahedron Lett. 1998, 39,
4425; (m) Zhu, Y.; Tu, Y.; Yu, H.; Shi, Y. Tetrahedron Lett.
1998, 39, 7819; (n) Wang, Z.-X.; Shi, Y. J. Org. Chem. 1997,
62, 8622; (o) Tu, Y.; Wong, Z.-X.; Shi, Y. J. Am. Chem. Soc.
1996, 118, 9806.
19. (a) Shing, T. K. M.; Leung, Y. C.; Luk, T. J. Org. Chem. 2005,
70, 7279; (b) Shing, T. K. M.; Leung, Y. C.; Yeung, K. W.
Tetrahedron Lett. 2003, 44, 9225.
20. For a review on 1,2-diacetals, see: Ley, S. V.; Baeschlin, D. K.;
Dixon, D. J.; Foster, A. C.; Ince, S. J.; Priepke, W. M. H.;
Reynolds, D. J. Chem. Rev. 2001, 101, 53.
21. Bennett, M.; Gill, G. B.; Pattenden, G.; Shuker, A. J.;
Stapleton, A. J. Chem. Soc., Perkin Trans. 1 1991, 929.
22. Montchamp, J. L.; Tian, F.; Hart, M. E.; Frost, J. W. J. Org.
Chem. 1996, 61, 3897.
23. Isidor, J. L.; Carlson, R. M. J. Org. Chem. 1973, 38, 554.
24. Lewis, M. D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc. 1982, 104,
9806.
25. Jacobsen, E. N.; Deng, L.; Furukawa, Y.; Martinez, L. E.
Tetrahedron 1994, 50, 4323.
26. (a) Song, C. E.; Oh, C. M.; Roh, E. J.; Lee, S. G.; Choi, J. H.
Tetrahedron: Asymmetry 1999, 10, 671; (b) Kobayashi, S.;
Ishitani, H.; Ueno, M. J. Am. Chem. Soc. 1998, 120, 431; (c)
Mukaiyama, T.; Shiina, I.; Uchiro, H.; Kobayashi, S. Bull.
Chem. Soc. Jpn. 1994, 67, 1708; (d) Sharpless, K. B.;
Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J.;
Jeong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.;
Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57, 2768.
27. (a) Mukaiyama, T.; Shiina, I.; Iwadare, H.; Saitoh, M.;
Nishimura, T.; Ohkawa, N.; Sakoh, H.; Nishimura, K.; Tani,
Y.; Hasegawa, M.; Yamada, K.; Saitoh, K. Chem.—Eur. J.
1999, 5, 121; (b) Kang, S. H.; Kim, C. M.; Youn, J.-H.
Tetrahedron Lett. 1999, 40, 3581; (c) Lee, K.-Y.; Kim, Y.-H.;
Park, M.-S.; Ham, W.-H. Tetrahedron Lett. 1998, 39, 8129;
(d) Bunnage, M. E.; Davies, S. G.; Goodwin, C. J. J. Chem.
Soc., Perkin Trans. 1 1994, 2385; (e) Commercon, A.;
Bezard, D.; Bernard, F.; Bourzat, J. D. Tetrahedron Lett.
1992, 33, 5185.
´
11. (a) Solladie-Cavallo, A.; Jierry, L.; Lupattelli, P.; Bovicelli, P.;
Antonioletti, R. Tetrahedron 2004, 60, 11375; (b) Solladie-
´
Cavallo, A.; Jierry, L.; Klein, A.; Schmitt, M.; Welter, R.
´
Tetrahedron: Asymmetry 2004, 15, 3891; (c) Solladie-
Cavallo, A.; Jierry, L.; Norouzi-Arasi, H.; Tahmassebi, D.
28. (a) Song, C. E.; Lee, S. W.; Roh, E. J.; Lee, S.-G.; Lee, W.-K.
Tetrahedron: Asymmetry 1998, 9, 983; (b) Farina, V.; Hauck,
S. I.; Walker, D. G. Synlett 1992, 761; (c) Ojima, I.; Habus,
I.; Zhao, M.; Zucco, M.; Park, Y. H.; Sun, C. M.; Brigaud, T.
Tetrahedron 1992, 48, 4323.
´
J. Fluorine Chem. 2004, 125, 1371; (d) Solladie-Cavallo, A.;
Bouerat, L.; Jierry, L. Eur. J. Org. Chem. 2001, 23, 4557; (e)
´
´
Solladie-Cavallo, A.; Jierry, L.; Bouerat, L.; Taillasson, P.
Tetrahedron: Asymmetry 2001, 12, 883; (f) Solladie-Cavallo,
´
´
29. Akbulut, N.; Hartsough, D.; Kim, J.-I.; Schuster, G. B. J. Org.
Chem. 1989, 54, 2549.
´
A.; Bouerat, L. Org. Lett. 2000, 2, 3531.
12. (a) Mukaiyama, T. Aldrichimica Acta 1996, 29, 59; (b) Palucki,
M.; McCormick, G. J.; Jacobsen, E. N. Tetrahedron Lett. 1995,
36, 5457; (c) Katsuki, T. Coord. Chem. Rev. 1995, 140, 189; (d)
Deng, L.; Jacobsen, E. N. J. Org. Chem. 1992, 57, 4320; (e)
Jacobsen, E. N.; Zhang, W.; Muci, A. R.; Ecker, J. R.; Deng,
30. Imashiro, R.; Seki, M. J. Org. Chem. 2004, 69, 4216.
31. (a) Shing, T. K. M.; Lee, C. M.; Lo, H. Y. Tetrahedron 2004, 60,
9179; (b) Shing, T. K. M.; Lee, C. M.; Lo, H. Y. Tetrahedron
Lett. 2001, 42, 8361; (c) Shing, T. K. M.; Lo, H. Y.; Mak,
T. C. W. Tetrahedron 1999, 55, 4643.

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6629
32. Acid 22 was not sensitive to the chiral shift reagent under
various solvents and concentrations. To overcome this prob-
lem, acid 22 was esterified by EtBr and DBU back to acetal
21, which gave better resolution of the separated peaks in the
1H NMR spectrum upon shift reagent addition.
33. Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am.
Chem. Soc. 1990, 112, 2801.
34. Yasukouchi, T.;Kanematsu, K.Tetrahedron Lett.1989, 30, 6559.
35. Sodeoka, M.; Yamada, H.; Shabasaki, M. J. Am. Chem. Soc.
1990, 112, 4906.