Asymmetric synthesis of (2/?,35)-2,3-epoxyamides via camphorderived sulfonium ylides

Article abstract of DOI:10.1039/a806189k

Enantiomerically enriched /ra;w-2,3-epoxyamides 3 were prepared by the reaction of aldehydes 2 with camphorderived chiral sulfbnium ylide 1 in good yields and moderate to good ee values. The absolute configuration of the reaction product is also determined by chemical transformations.

Full text of DOI:10.1039/a806189k

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Asymmetric synthesis of (2R,3S)-2,3-epoxyamides via camphor-
derived sulfonium ylides
Yong-Gui Zhou, Xue-Long Hou,* Li-Xin Dai, Li-Jun Xia and Ming-Hua Tang
Laboratory or Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received (in Cambridge) 5th August 1998, Accepted 10th November 1998
Enantiomerically enriched trans-2,3-epoxyamides 3 were prepared by the reaction of aldehydes 2 with camphor-
derived chiral sulfonium ylide 1 in good yields and moderate to good ee values. The absolute configuration of
the reaction product is also determined by chemical transformations.
Epoxides are versatile intermediates in organic chemistry. By
electrophilic or nucleophilic ring opening reactions, they can be
transformed to 1,2-difunctionalized systems or form new C–C
bonds.1,2 The development of methods for the preparation of
this type of compound is always a subject of great challenge.
The recorded methods for this aim are chiefly as follows: (a)
enantiofacially selective oxidation of a prochiral C᎐C bond;3
᎐
(b) enantioselective alkylidenation of a C᎐O bond, such as via
᎐
an ylide route or a Darzens reaction. Although the former
method has obtained much success, the structure requirements
of the substrates and using dangerous oxidative reagents are
limiting prerequisites. The latter strategy provides an alternative
approach in solving this problem. Enantioselective epoxidation
via an ylide route is an approach easy to perform but relatively
undeveloped to date. At present, only benzylidene transfer has
been realized successfully via the chiral ylide route.4 However
synthetically useful 2,3-epoxyesters cannot be prepared by the
reaction of ylides and aldehydes because of low reactivity.5 In
1966, Ratts and his co-workers reported the reaction of amide-
stabilized ylides with aldehydes, and afforded trans-2,3-epoxy-
amides.6a In 1990, Valpuesta-Fernandez and Lopez-Herrera6b
reported that the amide-stabilized sulfonium ylide reacted with
chiral aldehydes in good stereoselectivities (single trans isomers,
>92% de) and excellent yields. Subsequently further work7 on
other substrate-induced and stereoselective ring-opening of
products was performed in their laboratory, and high diastereo-
selectivities were obtained. Our research on the preparation of
functionalized optically active epoxides,8 combined with our
experiences in chiral sulfonium ylide chemistry,9 led us to
explore enantioselective synthesis of 2,3-epoxyamides by the
reaction of aldehydes and a stabilized chiral sulfonium ylide.
We disclose herein our methods for preparing (2R,3S)-
epoxyamides through chiral sulfonium ylides with excellent
yields, exclusive trans-configuration and moderate to good ee
values.
Scheme 1 Condition A: KOH, MeCN, RT; Condition B: NaOH (10%
aq), DCM, 0 ЊC.
and 1b (entries 1 and 3). In addition, we also examined liquid–
liquid phase transfer conditions (Scheme 1) (Condition B: CH2-
Cl2, NaOH 10% aq, 0 ЊC); the result is also shown in Table 1.
From entries 3 and 4 we found that chemical yields and ee
values from liquid–liquid and solid–liquid phase transfer con-
dition are the same. When other aldehydes such as 2a and 2f
were used, we found that the chemical yields from solid–liquid
phase conditions are lower than those from liquid–liquid phase
conditions, however, the ee values are the same. With regard to
p-nitrobenzaldehyde (2g) and nicotinealdehyde (pyridine-3-
carbaldehyde, 2h), the reaction under solid–liquid phase trans-
fer conditions is complex, and only trace products were
obtained. This may be explained by the fact that active alde-
hydes can undergo side reactions, such as the Cannizarro reac-
tion, due to contact with strong solid base KOH under solid–
liquid phase transfer conditions. However, under liquid–liquid
phase transfer conditions, the aldehydes are in the organic
phase (CH2Cl2), and the base is in the aqueous phase. There-
fore, liquid–liquid phase transfer conditions are the best choice.
The results for several substrates are summarized in Table 1.
From Table 1 we found that all kind of aldehydes, for
example, aryl, heteroaryl and aliphatic, reacted with chiral sul-
fonium salts under liquid–liquid phase transfer conditions to
afford the desired products in good to excellent chemical yields.
The asymmetric induction is moderate to good (from 10.9% to
71.5%) and the highest ee (71.5% ee) was obtained in the reac-
tion of benzaldehyde 2a. Only low ee values are obtained for
aliphatic aldehydes (entry 14 and 15). At present, we cannot
In our previous papers on asymmetric epoxidation9a of aro-
matic aldehydes and aziridination9b of N-tosylimines via the
sulfonium ylide route, we found that camphor-derived sulfides
were good chiral reagents, so camphor-derived chiral sulfonium
salts 1a, 1b and 1c were easily prepared by the reaction of chiral
sulfide
(ϩ)-exo-3-(methylthio)-1,7,7-trimethylbicyclo[2.2.1]-
heptan-2-ol10 with the corresponding α-bromoacetamides
respectively. We then used sulfonium salts 1 to perform this
reaction under solid–liquid phase transfer conditions (Scheme
1) (Condition A: KOH, CH3CN, RT). The model substrate is
p-chlorobenzaldehyde 2b. The results are shown in Table 1.
It was found that under the same conditions, ylides generated
from chiral sulfonium salts 1 reacted smoothly with aldehyde 2b
to give the optically active trans-epoxyamides in good yield. But
the yield and ee value of 1c (entry 2) are lower than those of 1a
J. Chem. Soc., Perkin Trans. 1, 1999, 77–80
77

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Table 1 Synthesis of chiral 3 by asymmetric epoxidation of aldehydes 2 with sulfonium salts 1 under phase transfer conditionsa
Yield (%)c
(product)
Entry
R in 2
R in 1
Conditionsb
Ee (%)d
Configurationf
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
C6H5
Me
-(CH2)5-
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Me
Et
Et
Et
A
A
A
B
A
B
A
B
A
A
B
B
B
B
B
B
88 (3ab)
68 (3cb)
89 (3bb)
92 (3bb)
61 (3ba)
93 (3ba)
49 (3bf)
90 (3bf)
93 (3bc)
96 (3be)
80 (3bh)
94 (3bg)
85 (3ag)
70 (3bi)
72 (3bj)
80 (3bd)
60.9
54.8
60.1
60.2
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
2R,3S
71.5
C6H5
66.4 (90.9e)
63.8
2R,3S
p-CF3C6H4
p-CF3C6H4
p-MeC6H4
4-Biphenyl
3-Pyridyl
p-NO2C6H4
p-NO2C6H4
Dodecyl
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
63.4
54.2
69.7
64.7
57.1
68.8 (95.4e)
10.9
Cyclohexyl
p-FC6H4
1.0
60.6
a All reactions were carried out in a ratio of aldehyde:sulfonium salt = 1:1.2 at a 0.5 mmol scale. b Condition A: CH3CN, KOH, RT; B: CH2Cl2,
NaOH (10% aq), 0 ЊC. c Isolated yields based on aldehydes; only trans isomers were obtained. d Determined by chiral HPLC on a Chiracel OD, OJ or
Chiralpak AD column. e The ee values refer to those after single recrystallization from n-hexane. f Determined by chemical transformations. The
configuration in parentheses is estimated by comparison with the phenyl analog. Signs of optical rotation of all compounds are (Ϫ).
explain this result. Attempts to use ester stabilized ylides in this
reaction failed and no sign of the existence of the cis-isomer in
all products has been revealed.
The absolute configuration of 2,3-epoxyamides 3a was deter-
mined by the following chemical transformations (Scheme 2).
Scheme 3
There are some examples of chiral, sulfide-catalyzed asym-
metric ylide epoxidation.13 They are catalytic with respect to the
chiral reagents. High ee values (>90%) and de (>98%) were
obtained with aromatic aldehydes, but lower de values (trans/
cis = 2/1) were obtained with aliphatic aldehydes, and the reac-
tion requires strict reaction conditions. The present asymmetric
epoxidation is a stoichiometric reaction but may represent a
promising practical approach to optically active epoxyamides
due to its compatibility with a wide range of substrates, high
yields and mild reaction conditions. Furthermore, the ylide pre-
cursor could be recovered in higher than 80% yield without loss
of optical purity, and could be reused. Although the ee value of
the product is not high (maximum 71.5%, entry 5), it could be
increased by a single recrystallization from n-hexane. For
example, the ee values of the products from entries 6 and 13 can
be increased from 66.4% to 90.9% and from 68.8% to 95.4%.
In conclusion, we developed a simple and practical approach
to optically active 2,3-epoxyamides via a chiral sulfonium ylide
route under phase transfer conditions. The absolute configur-
ation was assigned as (2R,3S) by known chemical transform-
ations. As can be seen, the title compound is a very useful
intermediate in organic synthesis.
Scheme 2
The 3-phenyl-2,3-dihydroxypropionamide 4 was synthesized
by Sharpless asymmetric dihydroxylation (AD);11 the configur-
ation is known to be (2S,3R). This compound was then trans-
formed to 2,3-epoxyamide 5 by a known literature method.12
On the basis of the sign of optical rotation and absolute
configuration (2S,3R) of compound 5, (Ϫ)-3a is therefore un-
ambiguously assigned as (2R,3S). The configurations of other
2,3-epoxyamides are assumed by the same signs of optical rota-
tions and the analogous structural similarity.
The enantiocontrolled reduction observed here can be visual-
ized by the mechanism shown in Scheme 3. Because the hydroxy
and the carbonyl of the amide can form an intramolecular
hydrogen bond, chiral sulfonium salt 1b is deprotonated to
afford a cyclic chiral sulfonium ylide 6, then the ylide attacks
the re-face of benzaldehyde followed by an immediate anti-
elimination to furnish trans-(2R,3S) 2,3-epoxyamide 3ba.
Experimental
The commercially available reagents were used as received
without further purification. Melting points are uncorrected.
1H NMR spectra were recorded on a Bruker AMX-300 (300
MHz) spectrometer in CDCl3 at room temperature. Chemical
shifts are given in parts per million downfield from tetramethyl-
78
J. Chem. Soc., Perkin Trans. 1, 1999, 77–80

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silane. Optical rotations were measured using a Perkin-Elmer
241 MC polarimeter with a thermally jacketed 10 cm cell at
20 ЊC (concentration c given as g per 100 mL). IR spectra were
recorded in KBr and measured in cmϪ1, using a Shimadzu
IR-440 infrared spectrophotometer. Mass spectra and high-
resolution mass spectra were taken using HP5989A and Finni-
gan MAT mass spectrometers, respectively. Elemental analyses
were performed on a Foss-Heraeus Vario EL instrument. Ee
values were determined by chiral HPLC on a Chiralcel OD, OJ
column or a Chiralpak AD column. Chromatographic separ-
ations were achieved using a liquid chromatograph constructed
from the following components: a Waters M510 pump operat-
ing at 0.7 mL minϪ1, a M440 UV detector (Waters, UV 254 or
214 nm), a Rheodyne M7725 injector and 250 × 4.6 mm i.d.
Chiralpak AD, Chiralcel OJ and Chiralcel OD columns. The
detector output was stored and reprocessed using a Perkin-
Elmer Nelson 1022. The temperature is about 20 ЊC. Chiral
trans-N,N-Diethyl-3-(biphenyl-4-yl)-2,3-epoxypropionamide
3be. (Found: C, 71.27; H, 7.86; N, 6.21; C13H17NO2 requires C,
71.21; H, 7.81; N, 6.39%); [α]D20 Ϫ87.5 (c, 1.40, acetone); H
1
NMR (300 MHz, CDCl3) δ 1.18 (3H, t, J 7.3, -CH2CH3), 1.25
(3H, t, J 7.3, -CH2CH3), 3.47 (m, -CH2CH3), 3.64 (1H, d, J 2.1,
CH), 4.14 (1H, d, J 1.8, CH), 7.42 (5H, m, ArH), 7.62 (4H, m,
ArH); MS m/z 296 (Mϩ ϩ 1, 50.5), 295 (M, 82.9), 238 (34.6),
165 (86), 152 (39), 100 (100), 72 (49.5), 56 (52.3); IR (KBr) 1653
(C᎐O). Chiralcel OD, hexane–i-PrOH (90:10); 25.3 min
᎐
(2R,3S), 28.3 min (2S,3R).
trans-1-[3-(4-Chlorophenyl)-2,3-epoxypropionyl]piperidine
3cb. (Found: C, 63.36; H, 6.23; N, 5.10; C14H16ClNO2 requires
C, 63.28; H, 6.07; N, 5.27%); [α]D20 Ϫ70.7 (c, 0.60, acetone); H
1
NMR (300 MHz, CDCl3) δ 1.55–1.75 (6H, m, -(CH2)3-), 3.40–
3.70 (4H, m, -NCH2-), 3.63 (1H, d, J 1.9, CH), 4.04 (1H, d,
J 1.9, CH), 7.29 (4H, m, ArH); MS m/z 265 (Mϩ, 13), 248 (15),
125 (50), 112 (42), 96 (100), 84 (37), 69 (55); IR (KBr) 1649
sulfide
(ϩ)-exo-3-(methylthio)-1,7,7-trimethylbicylo[2.2.1]-
heptan-2-ol,10 411 and α-bromo acetamides14 were prepared
according to the literature procedures. Sulfonium bromides 1a,
1b and 1c were prepared by the reaction of the corresponding
α-bromo acetamides with the chiral sulfide in a small amount
of acetone at room temp. with excellent yields.
(C᎐O). Chiralcel OJ, hexane–i-PrOH (80:20); 13.6 min
᎐
(2S,3R), 16.7 min (2R,3S).
trans-N,N-Diethyl-3-(4-chlorophenyl)-2,3-epoxypropionamide
3bb. (Found: C, 62.36; H, 6.36; N, 5.23; C13H16ClNO2 requires
C, 61.54; H, 6.38; N, 5.52%); [α]D20 Ϫ56.4 (c, 1.25, acetone); H
1
General procedure for epoxidation under liquid–liquid phase-
transfer conditions
NMR (300 MHz, CDCl3) δ 1.16 (3H, t, J 7.2, -CH2CH3), 1.22
(3H, t, J 7.2, -CH2CH3), 3.45 (4H, m, -CH2CH3), 3.54 (1H, d,
J 1.5, CH), 4.08 (1H, d, J 1.8, CH), 7.27 (2H, d, J 8.5, ArH),
7.35 (2H, d, J 8.7, ArH); 13C NMR (300 MHz, CDCl3) δ 12.95,
14.95, 40.98, 41.56, 56.99, 57.24, 127.05, 128.89, 165.38; MS
m/z 255 (Mϩ, 8, 37Cl), 253 (Mϩ, 27, 35Cl), 195 (50), 165 (43), 149
To a solution of aldehyde 2 (0.5 mmol) in dichloromethane (5
mL) was added the chiral sulfonium salt 1 (0.6 mmol) and 10%
aqueous NaOH (0.3 mL) at 0 ЊC. The reaction mixture was
stirred at 0 ЊC for 1 h. Water (2 mL) was then added and the
organic phase separated. The aqueous phase was extracted
twice with dichloromethane (2 × 5 mL). The organic layers
were washed with water, dried with MgSO4, concentrated and
chromatographed on a silica gel with a mixture of petroleum
ether and ethyl acetate (3:1) to give the pure product 3.
(58), 100 (59), 72 (97), 56 (87), 44 (100); IR (KBr) 1650 (C᎐O).
᎐
Chiralcel OD, hexane–i-PrOH (80:20); 11.1 min (2S,3R), 13.2
min (2R,3S).
trans-N,N-Diethyl-3-(4-fluorophenyl)-2,3-epoxypropionamide
3bd. (Found: C, 65.62; H, 6.75; N, 5.60; C13H16FNO2 requires
1
General procedure for epoxidation under solid–liquid phase-
transfer conditions
C, 65.81; H, 6.80; N, 5.90%); [α]D20 Ϫ27.0 (c, 1.05, acetone); H
NMR (300 MHz, CDCl3) δ 1.17 (3H, t, J 7.1, -CH2CH3), 1.24
(3H, t, J 7.3, -CH2CH3), 3.45 (4H, m, -CH2CH3), 3.55 (1H, d,
J 2.0, CH), 4.08 (1H, d, J 1.8, CH), 7.06 (2H, m, ArH), 7.31
(2H, m, ArH); MS m/z 238 (Mϩ ϩ 1, 16), 237 (Mϩ, 86), 220
(31), 149 (44), 128 (77), 100 (100), 72 (100), 56 (55); IR (KBr)
A 25 mL flask containing a magnetic stirring bar was charged
with aldehyde 2 (1.0 equiv.), sulfonium salt 1 (1.2 equiv.) and
acetonitrile (4 mL, reagent grade, it need not be dried before
use). Powdered KOH (1.2 equiv.) was subsequently added under
stirring. After the reaction was complete according to TLC, the
reaction mixture was filtered on a short neutral Al2O3 column
to remove the inorganic salt. The filtrate was concentrated and
chromatographed on a silica gel column with a mixture of light
petroleum ether and ethyl acetate (3:1) as the eluent to give
pure product 3.
1649 (C᎐O). Chiralcel OD, hexane–i-PrOH (90:10); 10.9 min
᎐
(2S,3R), 11.9 min (2R,3S).
trans-N,N-Diethyl-3-(4-methylphenyl)-2,3-epoxypropion-
amide 3bc. (Found: C, 72.08; H, 8.13; N, 5.65; C14H19NO2
requires C, 72.07; H, 8.21; N, 6.00%); [α]D20 Ϫ66.7 (c, 1.10,
1
acetone); H NMR (300 MHz, CDCl3) δ 1.16 (3H, t, J 7.1,
-CH2CH3), 1.20 (3H, t, J 7.2, -CH2CH3), 2.35 (3H, s, ArMe),
3.46 (4H, m, -CH2CH3), 3.58 (1H, d, J 2.1, CH), 4.04 (1H, d,
J 2.0, CH), 7.20 (4H, m, ArH); MS m/z 255 (Mϩ ϩ 1, 17), 233
(Mϩ, 76), 216 (18), 176 (30), 100 (92), 72 (100), 56 (99); IR
trans-N,N-Diethyl-3-phenyl-2,3-epoxypropionamide
3ba.
(Found: C, 71.27; H, 7.86; N, 6.21; C13H17NO2 requires C,
71.21; H, 7.81; N, 6.39%); [α]D20 Ϫ68.3 (c, 1.10, acetone); H
1
NMR (300 MHz, CDCl3) δ 1.16 (3H, t, J 7.1, -CH2CH3), 1.25
(3H, t, J 7.1, -CH2CH3), 3.42 (2H, q, J 7.1, -CH2CH3), 3.56 (2H,
q, J 7.1 -CH2CH3), 3.59 (1H, d, J 2.1, CH), 4.09 (1H, d, J 2.0,
CH), 7.36 (5H, m, ArH); MS m/z 220 (Mϩ ϩ 1, 16.6), 219 (M,
54.9), 200 (28.0), 147 (12.7), 100 (91.6), 91 (58.2), 72 (100), 56
(KBr) 1646 (C᎐O). Chiralcel OD, hexane–i-PrOH (95:5); 9.1
᎐
min (2S,3R), 10.3 min (2R,3S).
trans-N,N-Diethyl-3-(3-pyridyl)-2,3-epoxypropionamide 3bh.
1
[α]D20 Ϫ70.6 (c, 0.59, acetone); H NMR (300 MHz, CDCl3)
(78.5); IR (KBr) 1646 (C᎐O) cmϪ1. Chiralcel OD, hexane–i-
᎐
δ 1.09 (3H, t, J 7.2, -CH2CH3), 1.15 (3H, t, J 7.2, -CH2CH3),
3.36 (4H, m, -CH2CH3), 3.57 (1H, d, J 1.8, CH), 4.06 (1H, d,
J 1.8, CH), 7.25 (1H, m, ArH), 7.55 (1H, m, ArH), 8.50 (2H, m,
ArH); MS m/z (EI) 222 (Mϩ ϩ 2, 17.9), 221 (Mϩ ϩ 1, 100),
220.1212 (Mϩ, C12H16N2O2 requires 220.1254, 2.5), 163 (3), 110
PrOH (80:20); 9.9 min (2S,3R), 10.9 min (2R,3S).
trans-N,N-Dimethyl-3-(4-nitrophenyl)-2,3-epoxypropion-
amide 3ag. (Found: C, 55.75; H, 5.19; N, 11.93; C11H12N2O4
requires C, 55.93; H, 5.12; N, 11.86%); [α]D20 Ϫ80.1 (c, 1.08, acet-
1
(10), 72 (10); IR (KBr) 1650 (C᎐O). Chiralcel OD, hexane–i-
᎐
one); H NMR (300 MHz, CDCl3) δ 3.04 (3H, s, NCH3), 3.16
PrOH (80:20); 18.6 min (2S,3R), 23.7 min (2R,3S).
(3H, s, NCH3), 3.64 (1H, d, J 1.9, CH), 4.23 (1H, d, J 1.8, CH),
7.57 (2H, d, J 8.7, ArH), 8.24 (2H, d, J 8.7, ArH); MS m/z 236
(Mϩ, 6.2), 89 (20), 72 (100); IR (KBr) 1651 (C᎐O). Chiralcel
trans-N,N-Diethyl-3-(4-nitrophenyl)-2,3-epoxypropionamide
3bg. (Found: C, 58.75; H, 5.75; N, 10.47; C13H16N2O4 requires
᎐
OD, hexane–i-PrOH (60:40); 34.7 min (2S,3R), 36.7 min
(2R,3S).
1
C, 59.08; H, 6.10; N, 10.6%); [α]D20 Ϫ56.4 (c, 1.03, acetone); H
J. Chem. Soc., Perkin Trans. 1, 1999, 77–80
79

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NMR (300 MHz, CDCl3) δ 1.11 (3H, t, J 7.2, -CH2CH3), 1.16
(3H, t, J 7.2, -CH2CH3), 3.40 (4H, m, -CH2CH3), 3.51 (1H, d,
J 1.8, CH), 4.17 (1H, d, J 1.8, CH), 7.44 (2H, d, J 8.7, ArH),
8.16 (2H, d, J 8.7, ArH); MS m/z 265 (Mϩ ϩ 1, 100), 264 (Mϩ,
Acknowledgements
Financial support from the National Natural Science Found-
ation of China (29790127) and Chinese Academy of Sciences is
gratefully acknowledged.
22), 192 (29), 100 (48), 99 (31), 72 (49); IR (KBr) 1655 (C᎐O).
᎐
Chiralcel OD, hexane–i-PrOH (80:20); 23.9 min (2S,3R), 27.1
min (2R,3S).
References
1 For a review of epoxides in synthetic organic chemistry, see:
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F3O2 requires C, 58.53; H, 5.64; N, 4.88%); [α]D20 Ϫ42.1 (c, 1.00,
1
acetone); H NMR (300 MHz, CDCl3) δ 1.04 (3H, t, J 7.2,
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10), 264 (Mϩ, 30), 270 (53), 195 (28), 173 (32), 159 (62),
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M. Frohn, J.-R. Zhang and Y. Shi, J. Am. Chem. Soc., 1997, 119,
11224; ( f ) D. Yang, M.-K. Wong, Y.-C. Yip, X.-C. Wang, M.-W.
Tang, J.-H. Zheng and K.-K. Cheung, J. Am. Chem. Soc., 1998,
120, 5943; (g) D. Yang, Y.-C. Yip, M.-W. Tang, M.-K. Wong,
J.-H. Zheng and K.-K. Cheung, J. Am. Chem. Soc., 1996, 118, 491;
(h) D. Yang, X.-C. Wang, M.-K. Wong, Y.-C. Yip and M.-W.
Tang, J. Am. Chem. Soc., 1996, 118, 11311. Other routes: (i)
M. Bougauchi, S. Watanabe, T. Arai, H. Sasai and M. Shibasaki,
J. Am. Chem. Soc., 1997, 119, 2329; (j) B. Bhatia, S. Jain, A. De,
I. Bagchi and J. Iqbal, Tetrahedron Lett., 1996, 37, 7311; (k) S. Julia,
J. Masama, J. C. Vega, Angew. Chem., Int Ed. Engl., 1980, 19, 929
and references cited therein.
4 For a review on ylide asymmetric epoxidation: A.-H. Li, L.-X. Dai
and V. K. Aggarwal, Chem. Rev., 1997, 97, 2341 and references cited
therein.
5 B. M. Trost and L. S. Melvin, Sulfur Ylides, Academic Press,
New York, 1975.
6 (a) K. W. Ratts and A. N. Yao, J. Org. Chem., 1966, 31, 1689; (b)
M. Valpuesta-Fernandez and P. Duranta-Lanes, F. J. López-
Herrera, Tetrahedron, 1990, 46, 7911.
7 (a) F. J. López-Herrera, M. S. Pino-Gonzalez, F. Sarabia-Garcia,
A. Heras-López, J. J. Ortega-Alcantara and M. G. Pedraza-Cebrian,
Tetrahedron: Asymmetry, 1996, 7, 2065; (b) M. Valpuesta-
Fernandez, P. Duranta-Lanes and F. J. López-Herrera, Tetrahedron,
1993, 49, 9547; (c) F. J. López-Herrera, A. M. Heras-Lopez, M. S.
Pino-Gonzalez and F. Sarabia-García, J. Org. Chem., 1996, 61,
8839; (d) M. Valpuesta-Fernandez, P. Duranta-Lanes and F. J.
Lopez-Herrera, Tetrahedron Lett., 1995, 36, 4681.
8 (a) L.-X. Dai, B.-L. Lou and Y.-Z. Zhang, J. Am. Chem. Soc., 1988,
110, 5915; (b) J.-Y. Lai, F.-S. Wang, G.-Z. Guo and L.-X. Dai, J. Org.
Chem., 1993, 58, 6944; (c) L.-X. Dai, B.-L. Lou, Y.-Z. Zhang and
G.-Z. Guo, Tetrahedron Lett., 1986, 27, 4343.
9 (a) A.-H. Li, L.-X. Dai, X.-L. Hou, Y.-Z. Huang and F.-W. Li,
J. Org. Chem., 1996, 61, 489; (b) A.-H. Li, Y.-G. Zhou, L.-X. Dai,
X.-L. Hou, L.-J. Xia and L. Lin, Angew. Chem., Int. Ed. Engl., 1997,
36, 1317.
10 R. J. Goodridge, T. W. Hambely, R. K. Haynes and D. D. Ridley, J.
Org. Chem., 1988, 53, 2381.
100 (74), 72 (100), 56 (60); IR (KBr) 1647 (C᎐O). Chiralcel
᎐
OD, hexane–i-PrOH (80:20); 11.6 min (2S,3R), 15.8 min
(2R,3S).
trans-N,N-Dimethyl-3-(4-chlorophenyl)-2,3-epoxypropion-
1
amide 3ab. [α]D20 Ϫ14.2 (c, 1.25, acetone); H NMR (300 MHz,
CDCl3) δ 2.99 (3H, s, NCH3), 3.16 (3H, s, NCH3), 3.58 (1H, d,
J 2.0, CH), 3.96 (1H, d, J 2.0, CH), 7.26 (5H, m, ArH). Chiral-
cel OD, hexane–i-PrOH (80:20); 18.2 min (2S,3R), 19.5 min
(2R,3S).
1
trans-N,N-Diethyl-3-dodecyl-2,3-epoxypropionamide 3bi. H
NMR (300 MHz, CDCl3) δ 0.78 (3H, t, J 6.7, -CH2CH3), 1.03
(3H, t, J 7.1, -CH2CH3), 1.10–1.60 (23H, m, -(CH2)10CH3), 3.04
(1H, dt, J 2.5 and 5.6, CH), 3.22 (1H, d, J 2.1, CH), 3.43 (4H,
m, -CH2CH3); MS m/z 299 (Mϩ ϩ 2, 26.7), 298.2746 (Mϩ ϩ 1,
C19H37NO2 requires 298.2746, 100), 270 (53), 195 (28), 173 (32),
159 (62), 100 (74), 72 (100), 56 (60); IR (KBr) 1656 (C᎐O).
᎐
Chiralcel OD, hexane–i-PrOH (95:5); 10.8 min (2S,3R), 12.1
min (2R,3S).
trans-N,N-Diethyl-3-cyclohexyl-2,3-epoxypropionamide 3bj.
1H NMR (300 MHz, CDCl3) δ 1.10–1.40 (12H, m, -CH2CH2-
CH2- and CH3CH2-), 1.50–1.80 (5H, m, -CH2CHCH2-), 2.93
(1H, dd, J 2.1 and 6.6, CH), 3.40–3.60 (5H, m, -CH2CH3 and
CH); MS m/z 226 (Mϩ ϩ 1, 100), 225.1726 (Mϩ, C13H23NO2
requires 225.1729), 208 (45), 142 (8), 100 (15), 72 (25); IR (KBr)
1660 (C᎐O). Chiralcel OD, hexane–i-PrOH (95:5); 6.5 min
᎐
(2S,3R), 7.5 min (2R,3S).
The determination of absolute configuration of reaction product
Trimethyl orthoacetate (0.383 mL, 3.0 mmol) was added to a
stirred solution of 4 (475 mg, 2.0 mmol) and toluene-p-sulfonic
acid monohydrate (10 mg) in dichloromethane (12 mL). After
15 min, the mixture was evaporated and the residual MeOH
was removed at ca. 0.5 mmHg for 5 min. The residue was taken
up in dichloromethane (5 mL), to which TMSCl (0.41 mL, 2.83
mmol) was added. After 100 min, TLC showed almost com-
plete absence of orthoacetate, the mixture was heated to reflux
for 60 min, and then allowed to cool. Evaporation under reduced
pressure gave the crude acetoxy chloride as an oil. Potassium
carbonate (355 mg, 2.52 mmol) was added in 2 portions over 10
min to a vigorously stirred solution of the crude acetoxy chlor-
ide in MeOH (12 mL) at Ϫ20 ЊC. After 2 h, the mixture was
poured into a saturated aqueous NH4Cl solution (12 mL) and
extracted with dichloromethane (3 × 30 mL), dried over
Na2SO4. Purification of the residue by flash chromatography
(petroleum ether–ethyl acetate 3:1) afforded epoxyamide 5 as a
white solid 288 mg (66%). [α]D20 = 110Њ (c 0.98, acetone). The
absolute configuration of compounds 5 is (2S,3R). On the basis
of the sign of optical rotation and absolution configuration
(2S,3R) of compound 5, (Ϫ)-3a is therefore unambiguously
assigned as (2R,3S).
11 Y. L. Bennani and K. B. Sharpless, Tetrahedron Lett., 1993, 34, 2079.
12 J.-Q. Wang and W.-S. Tian, J. Chem. Soc., Perkin Trans. 1, 1996, 209.
13 (a) V. K. Aggarwal, H. Abdel-Rahman, R. V. H. Jones, H. Y. Lee
and B. D. Reid, J. Am. Chem. Soc., 1994, 116, 5973; (b) V. K.
Aggarwal, J. G. Ford, A. Thompson, R. V. H. Jones and M. C. H.
Standen, J. Am. Chem. Soc., 1996, 118, 7004; (c) V. K. Aggarwal, A.
Thompson, R. V. H. Jones and M. C. H. Standen, Tetrahedron:
Asymmetry, 1995, 6, 2557; (d) V. K. Aggarwal, M. Kalomirl, A. P.
Thomas, Tetrahedron: Asymmetry, 1994, 5, 723; (e) For an excellent
review, see: V. K. Aggarwal, Synlett, 1998, 329.
14 W. E. Weaver and W. M. Whaley, J. Am. Chem. Soc., 1947, 69, 515.
Paper 8/06189K
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