A convenient, room-temperature-organic base protocol for preparing chiral 3-(enoyl)-1,3-oxazolidin-2-ones

Article abstract of DOI:10.1002/1522-2675(200211)85:11<3616::AID-HLCA3616>3.0.CO;2-O

In this study, we developed a new protocol for the preparation of the chiral 3-[(E)-enoyl]-1,3-oxazolidin-2-ones under the ultimately simple reaction conditions starting with the corresponding enoyl chlorides and 1.3-oxazolidin-2-ones with Et₃N

Full text of DOI:10.1002/1522-2675(200211)85:11<3616::AID-HLCA3616>3.0.CO;2-O

3616
Helvetica Chimica Acta Vol. 85 (2002)
A Convenient, Room-Temperature Organic Base Protocol for
Preparing Chiral 3-(Enoyl)-1,3-oxazolidin-2-ones
by Vadim A. Soloshonok*a)b), Hisanori Uekia), Changchun Jianga), Chaozhong Caib), and Victor J. Hruby*b)
a) Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019
b) Department of Chemistry, University of Arizona, Tucson, AZ 85721
Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday. Our warmest regards and best wishes
for many more years of excellent science.
In this study, we developed a new protocol for the preparation of the chiral 3-[(E)-enoyl]-1,3-oxazolidin-2-
ones under the ultimately simple reaction conditions starting with the corresponding enoyl chlorides and 1,3-
oxazolidin-2-ones with Et3N/LiCl at room temperature. The method generally allows efficient preparation of
various derivatives regardless of the steric and electronic nature of the substituents on both the enoyl or the
oxazolidinone sites. Excellent yields, combined with the simplicity of the experimental procedures, render the
present method immediately useful for preparing the target compounds.
Introduction. Michael-addition reactions, generally defined, are among a handful
of truly fundamental reactions in organic chemistry [1]. Of particular interest are the
Michael-addition reactions between nucleophilic glycine equivalents and a,b-unsatu-
rated carboxylic acid derivatives, which represent the most methodologically concise
and generalized approach to the family of c-constrained1) five-C-atom amino acids
(Scheme 1). These reactions leading to the direct formation of glutamic (1) or
pyroglutamic acids (2) (depending on the work-up procedure) should be a reliable
source also for synthetic, tailor-made2) glutamines (3), prolines (4), ornithines (5), and
arginines (6) (Scheme 1)3). The issue of stereoselectivity in these reactions has received
a great deal of attention in the past [5]. Many research groups systematically studied
application of various chiral glycine equivalents (A in Scheme 1) or chiral Michael
acceptors (B in Scheme 1) to control the stereochemical outcome of such reactions.
In 1992, Seebach×s group first reported the ultimate level of stereoselectivity (only
one detectable stereoisomer) in the Michael addition reactions between (S)-
imidazolidinone 7 and 2,6-di(tert)-butyl)-4-(methoxy)phenyl esters 8 (Scheme 2)
giving rise to the corresponding pyroglutamic acids 2 of (2S,3R) (RˆAlk) and
(2S,3S) (Rˆi-Pr, Ar) absolute configuration. To account for the virtually complete
1
)
)
For recent reviews on c-constrained amino acids, see [2].
2
The rapidly growing list of amino acids isolated from various natural sources makes the terms unnatural,
or nonproteinogenic amino acids, which are most frequently used in the literature, dependent on the
success of specific scientific achievements. For instance, amino acids containing the xenobiotic element
fluorine have been shown to be synthesized by microorganisms [3]. Therefore, the time-independent term
tailor-made, meaning rationally designed/synthesized amino acids, in the absence of a better definition, is
more objective, and we suggested its use in the literature.
3
)
For a recent review on various synthetic transformations of pyroglutamic acid and its derivatives, see [4].

Helvetica Chimica Acta Vol. 85 (2002)
3617
Scheme 1
R
R
N
N
+
+
O
O
O
O
chiral
achiral
achiral
chiral
A
B
R
R
HOOC
COOH
NH2
COOH
O
N
H
2
1
O
R
R
COOH
NH2
H2N
COOH
N
H
3
4
R
R
H
N
H2N
COOH
NH2
H2N
COOH
NH
NH2
5
6
stereoselectivity in these addition reactions, Seebach suggested (based on molecular-
mechanics calculations and modeling) that only the s-cis conformer of 8 enters the
reaction with enolate 9, while the corresponding s-trans conformer of 8 does not react
with 9 due to steric shielding of its Cb-atom of the enoate system by the t-Bu group [6].
Drawing inspiration from these results and mechanistic rational, we assumed that
the geometric homogeneity of a glycine equivalent and conformational homogeneity of
a Michael acceptor might be of critical importance in controlling the stereochemical
outcome of the corresponding Michael-addition reactions. This idea turned out to be
very fruitful, allowing us to develop highly diastereoselective addition reactions
between the Ni-complex 10 and Michael acceptors 11 (Scheme 3) [7a]. Compounds 10
and 11 perfectly meet the requirements for geometric/conformational homogeneity.
Thus, due to its cyclic structure, complex 10 can give rise to only a (E)-enolate, while
Michael acceptors 11 exist in a s-cis configuration due to the unfavorable repulsive
steric and electrostatic interactions in the corresponding s-trans conformer [7]. The
synthetically advantageous characteristics of these reactions over other methods [5] are
that they occur at room temperature in the presence of nonchelating organic bases and
with virtually complete stereochemical outcome (> 98% d.e.). Thus, we have found that,
in the absence of any coordinating species, the Michael acceptors 11 were remarkably
effective in controlling both simple and face diastereoselectivity of these addition

3618
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 2
Me
Me
O
O
Me
Me
Me
Me
Me
Me
N
N
BuLi
THF, −78°
N
N
Li
Boc
Boc
7
9
OMe
Me
Me
Me
Me
Me
Me
R
O
O
8
R
Me
O
Me
Me
Me
N
2
O
COOH
5
N
H
N
COOAr
1'
R
Boc
2
R = Me, Et, PhCH2, i-Pr, Ph
(2S,5S,1'R) R = Alk
(2S,5S,1'S) R = i-Pr, Ar
reactions. However, while the conditions we found for the addition reactions render our
method practical and convenient for large-scale preparation of b-substituted glutamic/
pyroglutamic acids, the necessity of preparing starting Michael acceptors 11, according
to the standard Evans procedures [8], at À788 with BuLi, substantially compromised
the synthetic efficiency of our method as a whole. Recent reports improving on the
Evans procedures allow avoidance of the use of BuLi at À788, but require preparation
of the corresponding N-trimethylsilyl derivatives [9] or mixed anhydrides [10] to react
with acyl chlorides at high temperatures (>1158, long reaction times), or with 4-
substituted-1,3-oxazolidin-2-ones, at still low temperatures (À208), respectively.
Therefore, we wanted to find simple and synthetically efficient room-temperature
conditions for large-scale preparations of the starting 2-[(E)-enoyl]-4-phenyl-1,3-
oxazolidin-2-ones 11.
Results. We now report a very simple method for the preparation of Michael
acceptors 11 and related compounds (RˆPhCH2, i-Pr) 12 and 13 in high yields at room
temperature by direct reaction of 4-substituted 1,3-oxazolidin-2-ones 14 with the
corresponding acyl chlorides 15a e with Et3N as a base (Scheme 4).
For the reaction medium, we decided to use commercial-grade CHCl3 or CH2Cl2, as
these solvents could be used without prior drying. Our first attempt to conduct the
direct reaction between oxazolidin-2-one 14a with enoyl chloride 15a in a solution of
CHCl3 or CH2Cl2 at room temperature in the presence of Et3N was quite promising.

Helvetica Chimica Acta Vol. 85 (2002)
3619
Scheme 3
O
O
N
Ni
N
Me
N
O
O
O
O
O
O
O
R
N
R
N
10
(S)-11
Ph
Ph
(R)-11
DBU, DMF
DBU, DMF
N
N
O
N
O
N
N
O
N
O
Ni
Ni
R
R
H
O
O
H
H
H
O
O
Me
Me
N
N
O
O
Ph
Ph
O
O
(2R,3R) R = Alk
(2R,3S) R = i-Pr, Ar
(2S,3S) R = Alk
(2S,3R) R = i-Pr, Ar
Scheme 4
O
O
O
O
Et3N/LiCl,
'R
Cl
+
'R
N
N
CH2Cl2, r.t.
H
O
R
R
O
(S)- or (R)-14a−c
15a−j
(S)- or (R)-11a−j, 12, 13
14a R = Ph
14b R = PhCH2
14c R = i-Pr
15a R' = Ph
15b R' = 4-Cl−C6H4
11a R' = Ph
11b R' = 4-Cl−C6H4
11c R' = 3,4-Cl2−C6H3
11d R' = 2,6-F2−C6H3
11e R' = 3,5-F2−C6H3
11f R' = 4-CF3−C6H4
11g R' = 2-CF3−C6H4
11h R' = 4-NO2−C6H4
11i R' = 4-MeO−C6H4
11j R' = 2-MeO−C6H4
12a R = PhCH2; R' = Ph
13a R = i-Pr; R' = Ph
15c R' = 3,4-Cl2−C6H3
15d R' = 2,6-F2−C6H3
15e R' = 3,5-F2−C6H3
15f R' = 4-CF3−C6H4
15g R' = 2-CF3−C6H4
15h R' = 4-NO2−C6H4
15i R' = 4-MeO−C6H4
15j R' = 2-MeO−C6H4
Though the reaction occurred relatively slowly, the target product 11a was isolated in
good yield (90%) (Table 1, Entries 1 and 2). In the case of the reaction conducted in
CHCl3 containing about 1% of EtOH as a preservative, we observed formation (2
5%) of ethyl cinnamate, which substantially complicated the purification of the product

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Helvetica Chimica Acta Vol. 85 (2002)
Table 1. Reactions between 1,3-Oxazolidin-2-one 14a and Enoyl Chloride 15aa)
Entry
Base
t [h]
Ratiob) 14a/11a
1
2
3
4
5
6
Et3N
9/81
/59
11
24
147/53
141
11
1
Et3N
4/96c)
DABCOd)
DBUd)
Et(i-Pr)2N 2/88
Et3N
< 1/ > 99e)
a) All reactions were run in CH2Cl2 in the presence of 5 mol of the indicated base at r.t. Ratio (mol) 14a/15a
1.0 : 1.12. b) Determined by 1H-NMR on crude reaction mixtures. c) The product 11a was isolated in 90% yield.
d) For abbreviations, see text. e) The reaction was conducted with 5 mol of Et3N/LiCl.
11a. Therefore, we used CH2Cl2 as a solvent for the rest of the study. The results
suggested that the direct reaction between the corresponding enoyl chloride 15a and
the oxazolidinone 14a is synthetically feasible.
What we sought next were the proper reaction conditions to make this reaction
preparatively useful. To accelerate the reaction we decided to use a stronger base such
as Et(i-Pr)2N, 1,4-diazabicyclo[2.2.2]octane (DABCO), or 1,8-diazabicyclo[5.4.0]un-
dec-7-ene (DBU). In contrast to our expectations, the reactions conducted in the
presence of DABCO and DBU occurred at lower rates than the reaction with Et3N
(Entries 3 and 4vs. 1 ). On the other hand, the reaction with Et(i-Pr)2N proceeded at a
somewhat higher rate (Entry 5 vs. 1). Since Et(i-Pr)2N is much more expensive than
Et3N, a small increase in the reaction rate did not justify the application of this base.
Once again in this study drawing inspiration from Seebach×s results [11], we decided to
use LiCl as an additive. Thus, application of Et3N/LiCl resulted in a surprisingly
dramatic increase of the reaction rate and, therefore, in a complete conversion of the
starting compounds in less than 1h ( Entry 6). After a simple work-up procedure, the
target compound 11a was obtained in >98% yield. This 1-h reaction was success-
fully reproduced on up to a 4-g scale, indicating its synthetic efficiency and
practicability.
With these results in hand, we decided to check the generality of the method. The
results are summarized in Table 2. The reactions of Cl/F mono- and disubstituted
cinnamoyl chlorides 15b e with oxazolidinone 14a conducted under the optimized
standard conditions were complete in 1h, giving rise to the target products 11b e in
quantitative yields (Entries 2 5, Table 2). Introduction of electron-withdrawing
substituents on the phenyl ring of the starting enoyl chloride 15 was expected to
facilitate the reaction. Indeed, the reactions of 4-CF3- and 4-NO2-substituted
derivatives occurred at relatively higher rates than the reaction of unsubstituted
cinnamoyl chloride 15a (Entries 6 and 9). However, the reaction of the 2-CF3-
substituted derivative proceeded noticeably slower. Thus a 1-h reaction resulted in
about 90% conversion of the starting materials (Entry 7). Nevertheless, a prolonged
reaction time (overnight) allowed us to obtain the product 11g in quantitative yield
(Entry 8, Table 2). The same steric effect of ortho-substitution was observed in a series
of MeO-containing derivatives 15i,j. While the reaction of the para-substituted 15i was
complete in 1h ( Entry 10) the reaction of the 2-MeO-substituted 15j required a longer

Helvetica Chimica Acta Vol. 85 (2002)
3621
Table 2. Reactions between 1,3-Oxazolidin-2-ones 14a c and Enoyl Chlorides 15a ja)
Entry
(S)-4-R-1,3-
R
(E)-3-R'-2-Enoyl
R'
Product
Yieldb) [%]
Oxazolidin-2-one
chloride
1
2
3
4
5
6
7
8
9
10
11
12
13
14
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14a
14b
14c
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
PhCH2
i-Pr
15a
15b
15c
15d
15e
15f
15g
15g
15h
15i
Ph
11a
11a
11c
11d
11e
11f
11g
11g
11h
11i
11j
11j
12
> 98
> 98
> 98
> 98
> 98
> 98
4-ClÀC6H4
3,4-Cl2ÀC6H3
2,6-F2ÀC6H3
3,5-F2ÀC6H3
4-CF3ÀC6H4
2-CF3ÀC6H4
2-CF3ÀC6H4
4-NO2ÀC6H4
4-MeOÀC6H4
2-MeOÀC6H4
2-MeOÀC6H4
Ph
c
)
> 98d)
> 98
> 98
15j
15j
15a
15a
92c)
> 97d)
> 98
Ph
13
> 98
a) All reactions were run in CH2Cl2 for 1h in the presence of 5 mol of Et 3N/LiCl at room temperature. Ratio
(mol) 14/15 1.0 : 1.12. b) Isolated yield of pure (> 99% by 1H-NMR) product. c) About 90% conversion of the
starting compounds. d) The reaction was run overnight.
time for completion. Next, we conducted the reactions between cinnamoyl chloride 15a
and the most frequently used chiral oxazolidin-2-ones 14b,c containing PhCH2 and i-Pr
groups, respectively. Similar to the reaction with 14a, these acylations occurred at high
reaction rates, furnishing the target products 12 and 13 in excellent isolated yields
(Entries 13 and 14).
Conclusions. We have demonstrated that the preparation of chiral 3-[(E)-enoyl]-
1,3-oxazolidin-2-ones can be efficiently conducted at room temperature in a
commercial-grade solvent. The method generally allows practical large-scale prepara-
tion of various derivatives regardless of the steric and electronic nature of the
substituents on both the enoyl and the oxazolidinone sites. Simple reaction conditions
and excellent yields render the method immediately useful for preparing the target
compounds.
Experimental Part
General. All reagents and solvents, unless otherwise stated, are commercially available and were used as
received. The known compounds were confirmed by 1H-NMR, and the new compounds were characterized by
1H-, 19F-, 13C-NMR, optical rotation, and HR-MS. M.ps.: uncorrected; obtained in open capillaries. Optical
rotation: Jasco P-1010 polarimeter; measured at r.t. in commercial-grade CHCl3 containing 1% EtOH as
preservative. 1H-, 13C-, and 19F-NMR: Varian 300; measured at 299.94, 75.4, and 282 MHz, resp. in CDCl3;
Me4Si, CDCl3, and CCl3F as internal standards; d in ppm and J in Hz. HR-MS: Jeol HX110A.
General Procedure for the Reactions of 4-Substituted 1,3-Oxazolidin-2-ones 14a c with 3-Substituted (E)-
Prop-2-enoyl Chlorides 15a j. Synthesis of 3-[(E)-Enoyl]-1,3-oxazolidin-2-ones 11a j, 12, and 13. A
suspension of the corresponding a,b-unsaturated acid (1.05 equiv.) in SOCl2 (8 equiv.) was refluxed until a
homogeneous soln. was formed (ca. 5 h). The resulting soln. was cooled to r.t. and evaporated several times with
CH2Cl2 to give a residue free of SOCl2 and HCl. To a soln. of the acyl chloride 15a j (1.12 equiv.) thus prepared

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Helvetica Chimica Acta Vol. 85 (2002)
in CH2Cl2, the corresponding oxazolidinone 14a c (1.0 equiv.), LiCl (5 equiv.), and Et3N (5 equiv.) were added
at r.t. The mixture was stirred for 1h (or longer, see Table 2) and quenched by adding 1n HCl soln. The org.
phase was washed with sat. NaHCO3 soln. and brine, and dried (MgSO4). Filtration and evaporation of the org.
phase gave the crude product, which can be purified by column chromatography (SiO2, AcOEt/hexanes) or
recrystallized from AcOEt/hexanes. Yields of the products 11a j, 12, and 13 are given in Table 2, the physico-
chemical, chiroptical, and spectral data are listed below.
(R)-4-Phenyl-3-[(E)-3-phenylprop-2-enoyl]-1,3-oxazolidin-2-one ((R)-11a) [1 2].1H-NMR: 4.33 (part of
ABX, J ˆ 9.0, 3.9, 1H); 4.75 ( t, J ˆ 8.8, 1H); 5.57 (part of ABX, J ˆ 8.8, 3.9, 1H); 7.38 7.40 ( m, 7 H); 7.58 7.61
(m, 3 H); 7.79, 7.94 (AB, J ˆ 15.9, 2 H).
(R)-3-[(E)-3-(4-Chlorophenyl)prop-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one ((R)-11b). M.p. 135.0
135.58. [a]2D5 ˆ ‡21.2 (c ˆ 1.4). 1H-NMR: 4.33 (dd, J ˆ 9.0, 3.9, 1H); 4.75 ( t, J ˆ 8.8, 1H); 5.56 ( dd, J ˆ 8.8,
3.9, 1H); 7.34 7.40 ( m, 7 H); 7.52 (d, J ˆ 8.5, 1H); 7.72 ( d, J ˆ 15.9, 1 H); 7.91 (d, J ˆ 15.9, 1 H). 13C-NMR: 57.8;
70.0; 117.3; 126.0; 128.7; 129.1; 129.2; 129.7; 132.9; 136.6; 138.9; 145.1; 153.8; 164.5. FAB-HR-MS: 328.0740 (calc.
‡
for C18H15ClNO3, [M ‡ H] ; found 328.0739).
(S)-3-[(E)-3-(3,4-Dichlorophenyl)prop-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one ((S)-11c). M.p. 148.0
148.58. [a]2D5 ˆ 25.9 (c ˆ 1.0). H-NMR: 4.33 (dd, J ˆ 9.0, 3.9, 1H); 4.75 ( t, J ˆ 8.8, 1H); 5.56 ( dd, J ˆ 8.8, 3.9,
1
1H); 7.34 7.40 ( m, 7 H); 7.52 (d, J ˆ 8.5, 2 H); 7.72 (d, J ˆ 15.9, 1 H); 7.91 (d, J ˆ 15.9, 1 H). 13C-NMR: 57.8;
70.0; 117.3; 126.0; 128.7; 129.1; 129.2; 129.7; 132.9; 136.6; 138.9; 145.1; 153.8; 164.5.
(S)-3-[(E)-3-(2,6-Difluorophenyl)prop-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one ((S)-11d). M.p. 168.0
168.5. [a]2D5 ˆ ‡34.4 (c ˆ 1.1). 1H-NMR: 4.33 (dd, J ˆ 8.8, 4.0, 1H); 4.75 ( t, J ˆ 8.8, 1H); 5.55 ( dd, J ˆ 8.8, 3.9,
1H); 6.93 ( m, 2 H); 7.26 7.44 (m, 6 H); 7.86, 8.15 (AB, J ˆ 16.1, 2 H). 19F-NMR: À108.8 (t, J ˆ 7.6 ) .
(S)-3-[(E)-3-(3,5-Difluorophenyl)prop-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one ((S)-11e). M.p. 121.0
121.58. [a]2D5 ˆ ‡12.5 (c ˆ 1.3). 1H-NMR: 4.34 (dd, J ˆ 8.8, 3.9, 1H); 4.58 ( t, J ˆ 8.8, 1H); 5.54 ( dd, J ˆ 8.8,
3.9, 1H); 6.83 ( m, 1H); 7.08 ( m, 2 H); 7.30 7.44 (m, 5 H); 7.63, 7.90 (AB, J ˆ 15.6, 2 H). 19F-NMR: À108.4
(t, J ˆ 7.6 ) .
(S)-4-Phenyl-3-{(E)-3-[4-(trifluoromethyl)phenyl]prop-2-enoyl}-1,3-oxazolidin-2-one ((S)-11f). M.p.
112.0 113.08. [a]D25 ˆ ‡20.2 (c ˆ 1.4). 1H-NMR: 4.35 (part of ABX, J ˆ 9.0, 3.9, 1H); 4.77 ( t, J ˆ 8.7, 1H);
5.56 (part of ABX, J ˆ 8.7, 3.9, 1H); 7.32 7.44 ( m, 5 H); 7.63, 7.69 (AB, J ˆ 8.4, 4 H); 7.77, 8.00 (AB, J ˆ 15.6,
2 H). 13C-NMR: 57.9; 70.1; 119.3; 125.8 (q, J ˆ 3.0); 126.0; 128.7; 128.8; 129.2; 137.8; 138.8; 144.6; 153.8; 164.3;
the resonance of CF3 was not observed due to its low intensitiy. 19F-NMR: À64.0 (s). FAB-HR-MS: 362.1004
‡
(calc. C19h15F3NO3 [M ‡ H] : found 362.1004).
(S)-4-Phenyl-3-{(E)-3-[2-(trifluoromethyl)phenyl]prop-2-enoyl}-1,3-oxazolidin-2-one ((S)-11g). M.p.
1
80.0 80.58. [a]2D5 ˆ À7.1( c ˆ 1.0). H-NMR: 4.34 (part of ABX, J ˆ 8.8, 3.9, 1H); 4.76 ( t, J ˆ 8.8, 1H); 5.55
(part of ABX, J ˆ 8.8, 3.9, 1H); 7.26 7.45 ( m, 5 H); 7.48 (t, J ˆ 7.45, 1H); 7.58 ( t, J ˆ 6.8, 1H); 7.68 ( dd, J ˆ 8.3,
0.7, 1H); 7.85 ( d, J ˆ 7.82, 1H); 7.90 ( d, J ˆ 15.5, 1 H); 8.15 (dq, J ˆ 15.5, 2.08, 1 H). 19F-NMR: À58.0 (s). FAB-
‡
HR-MS: 362.1004 (calc. for C19H15F3NO3, [M ‡ H] ; found 362.1004).
(S)-3-[(E)-3-(4-Nitrophenyl)prop-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one ((S)-11h). M.p. 191.0 191.58.
[a]2D5 ˆ À24.1( c ˆ 1.5). 1H-NMR: 4.36 (part of ABX, J ˆ 9.0, 3.9, 1H); 4.78 ( t, J ˆ 8.8, 1H); 5.56 (part of ABX,
J ˆ 8.8, 3.9, 1H); 7.31 7.45 ( m, 5 H); 7.68 7.80 (m, 3 H); 8.04 (d, J ˆ 15.8, 1 H); 8.20 8.27 (m, 2 H). 13C-NMR:
57.8; 70.0; 120.8; 123.9; 125.8; 128.7; 128.9; 129.0; 138.4; 140.2; 143.0; 148.4; 153.5; 163.6.
(S)-3-[(E)-3-(4-Methoxyphenyl)prop-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one ((S)-11i). M.p. 145.0
146.08. [a]2D5 ˆ À46.1( c ˆ 1.0). 1H-NMR: 3.84 (s, 3 H); 4.31(part of ABX, J ˆ 3.8, 8.9, 1H); 4.74 ( t, J ˆ 9.0,
1H); 5.56 (part of ABX, J ˆ 9.0, 3.9, 1H); 6.90 (part of AB, J ˆ 8.8, 2 H); 7.33 7.42 (m, 5 H); 7.55 (part of AB,
J ˆ 9.0, 2 H); 7.75, 7.82 (AB, J ˆ 15.9, 2 H). 13C-NMR: 55.4; 57.9; 69.9; 114.2; 114.3; 126.0; 127.3; 128.6; 129.2;
‡
130.5; 139.2; 146.6; 153.9; 161.8; 165.0. FAB-HR-MS: 324.1236 (calc. for C19H18NO4, [M ‡ H] ; found
324.1224).
(S)-3-[(E)-3-(2-Methoxyphenyl)prop-2-enoyl]-4-phenyl-1,3-oxazolidin-2-one ((S)-11j). M.p. 144.0
145.08. [a]2D5 ˆ ‡47.8 (c ˆ 1.2). 1H-NMR: 3.87 (s, 3 H); 4.31(part of ABX, J ˆ 8.8, 3.9, 1H); 4.73 ( t, J ˆ 8.8,
1H); 5.56 (part of ABX, J ˆ 3.9, 8.8, 1H); 6.89 (part of AB, J ˆ 8.2, 1.1, 2 H); 6.95 (tdd, J ˆ 7.8, 1.1, 0.5, 1 H);
7.26 7.45 (m, 6 H); 7.61( ddt, J ˆ 7.7, 1.8, 0.5, 1 H); 7.99 (d, J ˆ 15.9, 1 H); 8.13 (d, J ˆ 15.9, 1 H). 13C-NMR: 55.4;
55.8; 69.8; 110.1; 116.9; 120.5; 123.3; 125.8; 128.4; 128.9; 129.2; 131.8; 139.0; 141.8; 153.6; 158.4; 164.9. FAB-HR-
‡
MS: 324.1236 (calc. for C19H18NO4, [M ‡ H] ; found 324.1227).
(S)-4-Benzyl-3-[(E)-3-(phenylprop-2-enoyl]-1,3-oxazolidin-2-one ((S)-12) [1 3].1H-NMR: 2.86, 3.38
(ABX, J ˆ 13.4, 9.5, 3.2, 2 H); 4.19 4.29 (m, 2 H); 4.77 4.85 (m, 1H); 7.24 7.44 ( m, 8 H); 7.63 7.67
(m, 2 H); 7.93 (s, 2 H).

Helvetica Chimica Acta Vol. 85 (2002)
3623
(S)-4-Isopropyl-3-[(E)-3-phenylprop-2-enoyl]-1,3-oxazolidin-2-one ((S)-13) [8]. 1H-NMR: 0.92 (d, J ˆ 7.1,
3 H); 0.96 (d, J ˆ 6.8, 3 H); 2.41 2.50 ( m, 1H); 4.25, 4.32 (part of ABX, J ˆ 9.0, 8.3, 3.2, 2 H); 4.54 4.59
(m, 1H); 7.39 7.41( m, 3 H); 7.60 7.65 (m, 2 H); 7.85, 7.96 (AB, J ˆ 15.6, 2 H).
The work was supported by the grants from U.S. Public Health Service Grant and the National Institute of
Drug Abuse DA 06284, DA 13449, and DK 17420 (V.J.H.). The views expressed are those of the authors and not
necessarily those of the USPHS. V.A.S. thanks the Department of Chemistry and Biochemistry, University of
Oklahoma for a generous start-up fund.
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Received May 31, 2002