Investigations into the parallel kinetic resolution of 2-phenylpropanoyl chloride using quasi-enantiomeric oxazolidinones

Article abstract of DOI:10.1016/j.tetasy.2007.01.002

The resolution of 2-phenylpropanoyl chloride using an equimolar combination of quasi-enantiomeric oxazolidinones is discussed. The levels of diastereoselectivity were found to be dependent upon the structural nature of the metallated oxazolidinone, temperature and metal counter-ion.

Full text of DOI:10.1016/j.tetasy.2007.01.002

Tetrahedron: Asymmetry 17 (2006) 3386–3399
Investigations into the parallel kinetic resolution of
2-phenylpropanoyl chloride using quasi-enantiomeric oxazolidinones
Sameer Chavda,a Elliot Coulbeck,a Gregory S. Coumbarides,b Marco Dingjan,a,b
Jason Eames,a,* Stephanos Ghilagaberb and Yonas Yohannesb
aDepartment of Chemistry, University of Hull, Cottingham Road, Kingston upon Hull HU6 7RX, UK
bDepartment of Chemistry, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
Received 16 November 2006; accepted 5 January 2007
Abstract—The resolution of 2-phenylpropanoyl chloride using an equimolar combination of quasi-enantiomeric oxazolidinones is
discussed. The levels of diastereoselectivity were found to be dependent upon the structural nature of the metallated oxazolidinone,
temperature and metal counter-ion.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
Whereas Davies13 has shown the use of activated acid chlo-
rides, such as O-acetyl mandelic chloride rac-3 can give the
corresponding adduct anti-7 with moderate to good levels
of diastereoselectivity (Scheme 1).
The synthesis of enantiomerically pure profens,1 such as
ibuprofen2 and naproxen,3 is well documented. In particu-
lar, the (S)-enantiomeric form has become pharmaceuti-
cally important due to its non-steroidal anti-inflammatory
properties.4 Over the last decade, a notable amount of
attention has been focused on the design of novel methods5
for their efficient industrial construction. More recently, the
use of chiral auxiliaries,6 such as Evans’ original oxazolidi-
nones7 has attracted some attention. These approaches
have focussed on the use of diastereoselective alkylation
of chiral enolates8 and simple derivatizations of substituted
oxazolidinones. Of these two approaches, diastereoselective
alkylation has been shown to give excellent levels of stereo-
control with considerable predictability.9 By comparison,
derivatization of enantiomerically pure lithiated oxazolidi-
nones by the addition of racemic acid chlorides, even
though synthetically shorter, is much less documented due
to poor diastereocontrol.10 For example, Fukuzawa11and
Bettoni12 have shown the resolution of 2-phenylpropanoyl
chloride rac-1 and (4-chlorophenoxy)propanoyl chloride
rac-2, respectively, using a lithiated Evans oxazolidinone
[derived from the deprotonation of (S)-4 with n-butyl lith-
ium], gave the corresponding adducts 5 and 6 with no levels
of diastereocontrol (Scheme 1).
Davies has also investigated this poor stereodiscrimina-
tion,13 and has discovered that SuperQuat oxazolidi-
nones,14 such as (S)-8, are capable of kinetically resolving
O-acetyl mandelic chloride rac-3 and related 2-acetoxy-2-
cyclohexylacetyl chloride rac-10 with good to high levels
of diastereoselectivity, to give the corresponding anti-ad-
ducts 9 and 11 in high yields (95% and 88%, respectively)
with excellent levels of diastereoisomeric control (Scheme
2). By contrast, Fukuzawa11 has used an alternative cou-
pling strategy15 to improve the levels of diastereocontrol
by the use of a copper (II) chloride mediated coupling of
N-silylated oxazolidinone (S)-12 and 2-phenylpropanoyl
chloride rac-1 (Scheme 2). This proved moderately success-
ful, leading to the complementary syn-adduct 5 in a 49%
yield as the major diastereoisomer (Scheme 2).
2. Results and discussion
Over the last few years, we have become interested16 in the
synthesis of enantiomerically pure profen adducts.17 In
particular, we have also probed17a the resolution of 2-phen-
ylpropionic acid 10 by the addition of the lithiated oxazo-
lidinone [derived from n-butyl lithium and (S)-4] to a
solution of 2-phenylpropanoyl chloride rac-3 (2 equiv) in
*
Corresponding author. Tel.: +44 1482 466401; fax: +44 1482 466410;
e-mail: j.eames@hull.ac.uk
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.01.002

S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
3387
O
O
O
O
Ph
Ph
O
HN
O
Cl
Cl
Cl
OAc
Me
rac-1
Me
Cl
i-Pr
(S)-4
rac-3
rac-2
O
O
O
O
1. n-BuLi,
THF, -78 oC
Ph
Me
Ph
H
N
O
N
O
(S)-4
2. (rac)-1
H
Me
i-Pr
syn-5
i-Pr
anti-5
50:50
O
O
O
O
1. n-BuLi,
O
O
THF, -78 oC
N
O
N
O
(S)-4
(S)-4
H
Me
Me
H
2. (rac)-2
Cl
50:50; 78%
Cl
i-Pr
i-Pr
syn-6
anti-6
O
O
O
H
O
1. n-BuLi,
THF, -78 oC
Ph
Ph
N
O
N
O
2. (rac)-3
AcO
H
OAc
i-Pr
i-Pr
anti-7
syn-7
70:30; 89%
Scheme 1. Kinetic resolution of acid chlorides 1, 2 and 3 using (S)-4.
O
O
O
95%
O
O
1. n-BuLi,
Ph
AcO
Ph
THF, -78 oC
HN
O
N
O
N
O
2.
Ph
COCl
(rac)-3
H
H
OAc
i-Pr
i-Pr
i-Pr
syn-9
OAc
(S)-8
anti-9
83:17
O
O
O
88%
1. n-BuLi,
THF, -78 oC
O
O
Cy
Cy
HN
O
N
O
N
O
AcO
H
2.
H
OAc
Cy
COCl
(rac)-10
i-Pr
i-Pr
O
i-Pr
syn-8
OAc
(S)-8
anti-11
91:9
49%
O
O
O
O
CuCl2, 25 oC
hexane, 72 h
Me3Si
Ph
Ph
N
O
N
O
N
O
Ph
COCl
(rac)-1
Me
H
H
Me
i-Pr
(S)-12
i-Pr
i-Pr
Me
syn-5
anti-5
25:75
Scheme 2. Kinetic resolution of acid chlorides 1, 3 and 10 using 8 and 12.

3388
S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
THF at ꢀ78 ꢁC, and found in line with Fukuzawa’s re-
ports11 that a near equimolar mixture of both adducts anti-
and syn-5 were formed in a 47% yield (Scheme 3). The
assignment of stereochemistry was achieved by hydrolyzing
each adduct, anti- and syn-5, using a combination of LiOH
In an attempt to gain a better understanding of this process,
we next investigated the mutual kinetic resolution of 2-phen-
ylpropanoyl chloride rac-1 using a racemic mixture of oxa-
zolidinone rac-4 (Scheme 4). This proved to be moderately
diastereoselective, favouring the formation of the anti-ad-
duct 5 with 40% diastereoisomeric excess in 60% yield
(Scheme 4). The diastereoselectivity was found to decrease
with an increase of the enantiomeric excess of the parent
oxazolidinone (S)-4; the use of racemic oxazolidinone 4
gave the highest level of diastereoselectivity (Scheme 4).
This type of behaviour was shown to occur with other re-
18
and H2O2 to give the corresponding (S)- and (R)-enanti-
omers of 2-phenylpropionic acid 10, respectively (Scheme
3). The absolute stereochemistry of these adducts, anti-
and syn-5, was assigned by the comparison of the specific
rotation of (S)-10 and (R)-10 with known literature
values.19,20
O
O
O
O
1. n-BuLi,
THF, -78 o
C
Ph
Ph
N
O
N
O
(S)-4
2. rac-1
(2 equiv.)
Me
H
H
Me
i-Pr
i-Pr
syn-5
anti-5
52:48; 47%
O
O
O
Ph
Me
LiOH, H2O
H2O2, THF
Ph
N
O
O
OH
H
Me
H
i-Pr
(+)-(S)-13; >98% ee; 99%
anti-5
O
O
O
Ph
LiOH, H2O
H2O2, THF
Ph
N
OH
H
Me
i-Pr
H
Me
syn-5
(-)-(R)-13; >98% ee; 99%
Scheme 3. Hydrolysis of anti- and syn-adducts 5.
O
O
O
O
O
1. n-BuLi,
2. (rac)-1
THF, -78 o
C
Ph
Ph
N
O
HN
R1
O
N
O
Me
H
H
Me
R1
R1
anti-(major)
syn-(minor)
O
O
O
O
O
HN
O
HN
O
HN
O
HN
O
HN
O
Ph
Me
Ph
i-Pr
EtO2C
Ph
4
15
14
16
17
Oxazolidinones
Using racemic
oxazolidinones
18; 34% d.e. (68%)
anti-:syn-
5; 40% d.e. (60%)
20; 18% d.e. (59%) 21; 12% d.e. (58%)
19; 18% d.e. (62%)
19; 0% d.e. (70%)
anti-:syn-a
anti-:syn-b
20; 0% d.e. (59%)
20; 0% d.e. (69%)
21; 0% d.e. (69%)
21; 14% d.e. (71%)
18; 0% d.e. (68%)
5; 0% d.e. (52%)
5; 4% d.e. (47%)
Using homochiral
oxazolidinones
18; 0% d.e. (70%) 19; 4% d.e. (70%)
aUsing 1 equivalent of rac-1; bUsing 2 equivalents of rac-1
Scheme 4. Mutual and kinetic resolution of racemic 2-phenylpropanoyl chloride 1 using oxazolidinones 4, 14, 15, 16 and 17.

S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
3389
O
O
O
O
O
1. n-BuLi,
THF, -n oC
Ph
Me
Ph
HN
O
N
O
N
O
2. (rac)-1
H
H
Me
i-Pr
i-Pr
i-Pr
anti-5
syn-5
rac-4
rac-anti-:syn-4
45:55 (52%) 33:67 (49%)
70:30 (60%) 70:30 (60%) 57:43 (65%)
-97 o
33:67 (50%)
+50 oC
0
oC
+25 oC
-29 o
C
-78 oC
Temperature
C
O
O
O
O
O
1. M-Base,
Ph
THF, -78 o
C
Ph
HN
O
N
O
N
O
2. (rac)-1
Me
H
H
Me
i-Pr
i-Pr
i-Pr
anti-5
(rac)-4
syn-5
M-Base
rac-anti-:syn-5
n-BuLi
KHMDS
NaHMDS
LiHMDS
64:36 (70%)
34:66 (70%)
38:62 (58%)
70:30 (60%)
Scheme 5. Variation in temperature, metal counter-ion and diastereoselectivity.
O
O
O
Ph
Me
1. n-BuLi, THF, n oC
N
O
HN
O
2.
O
H
H
i-Pr
i-Pr
Ph
(S)-4
anti-5
Cl
ratio: anti-:syn-5: >99:<1
(S)-1
Me
T = -78 oC; Yield = 40%
T = +25 oC; Yield = 25%
O
O
O
Ph
1. n-BuLi, THF, n oC
2.
N
O
HN
O
O
Me
H
H
i-Pr
i-Pr
Ph
Cl
(R)-4
syn-5
Me
(S)-1
ratio: syn-:anti-5: >99:<1
T = -78 oC; Yield = 30%
T = +25 oC; Yield = 31%
O
O
O
Ph
1. n-BuLi, THF, -78 o
2.
C
N
O
HN
O
O
Me
D
D
i-Pr
i-Pr
Ph
Cl
(rac)-4
anti-[D1]-5
Me
ratio: anti-:syn-[D1]-5: 65:35; 69%
rac-[D1]-1
([D]:[H] = 95:5)
([D]:[H] = 94:6)
Scheme 6. Stereospecific addition of (S)- and (R)-4 to acid chloride (S)-1.

3390
S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
lated oxazoldinones, such as racemic norephedrine, phenyl-
alanine, serine and phenylglycine derived oxazolidinones
rac-14, rac-15, rac-16 and rac-17. For these particular cases,
they gave better diastereoselectivity than their correspon-
ding enantiomerically pure derivatives (Scheme 4). The
exception being the phenylglycine derived oxazolidinone
rac-17, which gave similar levels of diastereocontrol for
both the mutual and kinetic resolutions (Scheme 4). The
levels of diastereoselectivity and facial selectivity were
found to be dependent on the reaction temperature; for
example, for oxazolidinone rac-4, there was a reversal of
diastereoselectivity favouring the formation of the anti-ad-
duct 5 at a low temperature (ꢀ97 ꢁC) through the corre-
sponding syn-adduct 5 at a higher temperature (+50 ꢁC)
(Scheme 5). The nature of the metal counterion associated
with the metallated oxazolidione was also shown to be
important in influencing the relative diastereoselectivity; a
lithium counterion favoured the formation of the anti-ad-
duct 5 (40% de), whereas, a sodium and potassium coun-
ter-ion favoured the formation of the corresponding syn-
adduct 5 with 32% and 24% diastereoisomeric excesses,
respectively (Scheme 5).21
syn-5, respectively, in 25–40% yields (>98% de) (Scheme
6). The lower yields at room temperature (+25 ꢁC) were
presumably due to the competitive deprotonation of the
acid chloride rac-1 and subsequent re-formation of the par-
ent oxazolidinone 4. This competitive deprotonation ap-
pears to be slowed sufficiently under the time scale of the
reaction by using the C(1)-deuterium-labelled acid chloride
[D1]-1 ([D]:[H] = 94:6), which gave the corresponding anti-
and syn-adducts [D1]-5 ([D]:[H] = 95:5) in higher yield
(Scheme 6). It is interesting to note, there appears to be lit-
tle or no primary kinetic isotope effect for the formation of
these adducts.
With this information in hand, we next investigated the
resolution of 2-phenylpropanoyl chloride rac-1 using an
equimolar combination of two complementary enantiome-
rically pure quasi-enantiomeric oxazolidinones. We chose
to study the use of structurally related quasi-enantiomeric
oxazolidinones, such as (4R,5S)-14 (in A) and (R)-17 (in
B) as potential surrogates for the (R)-enantiomer of 4 as
this should lead to a comparable diastereoselectivity as
with the parent rac-4 (Scheme 7). However, the use of an
equimolar mixture of these quasi-enantiomeric oxazolidi-
nones (S)-4 and (4R,5S)-14 (in A), and (S)-4 and (R)-17
(in B) as a mimic for the racemic oxazolidinone 4 gave
poorer levels of diastereoselectivity than the original mu-
tual kinetic resolution (Scheme 7). This was presumably
due to oxazolidinones (4R,5S)-14 and (R)-17 being non-
compatible as a complementary enantiomer to (S)-4 within
the original mutual kinetic resolution (Scheme 4).
This nucleophilic addition–elimination process appears to
be stereospecific and occurs with retention of configura-
tion; addition of enantiomerically pure lithiated oxazolidi-
nones [derived from the n-BuLi addition of (S)-4 and (R)-4,
respectively] to enantiomerically pure 2-phenylpropanoyl
chloride (S)-1 at both ꢀ78 and +25 ꢁC gave the corre-
sponding diastereoisomerically pure adducts anti- and
O
O
O
O
O
O
1. n-BuLi
Ph
Me
Ph
THF, -78 o
C
N
O
N
O
HN
R1
O
HN
R2
O
2.
Ph
O
H
H
Me
R1
anti-:syn-
R2
Cl
anti-:syn-
rac-1
Me
(2 equiv.)
B
A
O
O
O
O
HN
O
HN
O
HN
O
HN
O
i-Pr
Ph
i-Pr
Me
Ph
(S)-4
anti-:syn-5; 55:45; 62%
(S)-4
anti-:syn-5; 50:50; 54% anti-:syn-21; 56:44; 48%
(R)-17
(4R,5S)-14
anti-:syn-18; 55:45; 73%
O
O
C
D
O
O
HN
O
HN
O
HN
O
HN
O
Ph
Me
Ph
Ph
(S)-15
anti-:syn-19; 50:50; 58%
Ph
(S)-15
anti-:syn-21; 50:50; 58% anti-:syn-18; 67:33; 58% anti-:syn-18; 72:28; 59%
(R)-17
(4R,5S)-14
Scheme 7. Parallel resolution of rac-1 using an equimolar combination of quasi-enantiomeric oxazolidinones.

S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
3391
O
O
O
O
Ph
Me
Ph
N
O
N
O
H
H
Me
Me
Me
Ph
Ph
O
O
1. n-BuLi, THF, -78 o
2.
C
67:33
syn-18; 22%
HN
O
anti-18; 39%
HN
O
O
O
O
O
O
Ph
Me
Ph
Cl
Ph
Ph
Me
N
O
N
O
Ph
(S)-15
(1 equiv.)
Me (2 equiv.)
rac-1
H
Me
(4R,5S)-14
(1 equiv.)
H
Ph
syn-19; 19%
Ph
anti-19; 37%
72:28
Entry
anti-19:syn-19
anti-18:syn-18
oxazolidinones
15-(rac)a
1
2
rac-59:41 (44%)
14-raca
(rac)-67:33 (68%)
15 (S-)b
3
4
5
52:48 (70%)
67:33 (58%)
14-(4R,5S)b
50:50 (70%)
72:28 (59%)
14-(4R,5S)-(1 eq.)
+
15 (S)-(1 eq.)c
14-(4R,5S)-(0.5 eq.) + 15 (S)-(1.5 eq.)
14-(4R,5S)-(1.5 eq.) + 15 (S)-(0.5 eq.)
54:46 (73%)
78:22 (65%)
6
7
80:20 (69%)
64:36 (50%)
aMutual kinetic resolution; bKinetic resolution with 2 equivalents of rac-1; cParallel kinetic resolution
Scheme 8. Parallel resolution of rac-1 using a combination of quasi-enantiomeric oxazolidinones (4R,5S)-14 and (S)-15.
Probing two further quasi-enantiomeric combinations of
oxazolidinones (S)-15 and (R)-17 (in C), and (4R,5S)-14
and (S)-15 (in D) has shown that comparable diastereo-
selectivity can be achieved using a parallel kinetic resolution
approach (Scheme 7). The equimolar combination of oxa-
zolidinones (4R,5S)-14 and (S)-15 appears to mirror that of
each corresponding racemic pair of oxazolidinones 14 and
15, respectively (Scheme 7). Interestingly, the diastereo-
O
O
O
O
O
O
1. n-BuLi
Ph
Me
Ph
Me
THF, -78 o
C
N
O
N
O
HN
R1
O
HN
R2
O
2.
Ph
O
H
H
R1
R2
Cl
anti-:syn-
anti-:syn-
rac-1
Me
(2 equiv.)
O
E
O
O
F
O
HN
O
HN
O
HN
O
HN
O
Ph
EtO2C
Me
Ph
EtO2C
(R)-16
(R)-17
anti-:syn-21; 50:50; 40%
(R)-16
anti-:syn-20; 50:50; 60%
(4R,5S)-14
anti-:syn-18; 50:50; 70%
anti-:syn-20; 60:40; 55%
Scheme 9. Resolution of rac-1 using a combination of oxazolidinones.

3392
S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
selectivity for these addition processes were found to better
than that originally suggested from their individual mutual
kinetic resolutions (Scheme 4). The levels of diastereocon-
trol were evidently dependent on the presence of the chosen
surrogate enantiomer for each oxazolidinone, as without it,
the overall diastereoselectivity was reduced. In an attempt
to enhance the diastereoselectivity by promoting the appa-
rent compatibility between these lithiated oxazolidinones
(4R,5S)-14 and (S)-15 and the acid chloride rac-1 (in
Scheme 7), we chose to use an unequal amount of the par-
ent oxazolidinones (Scheme 8). We argued if a combination
of quasi-enantiomers were responsible for improving the
diastereocontrol, an increase in stereocontrol might be ex-
pected for the product derived from the minor lithiated
oxazolidinone, while a decrease in stereocontrol would be
expected for the product derived from the complementary
major oxazolidinone. Using an excess of the oxazolidinone
(4R,5S)-14, the diastereoselectivity of the minor oxazolidi-
none (S)-15 improved from 44% to 56% de in favour of
anti-adduct 19 (Scheme 8: entry 7), whereas, using an ex-
cess of the other oxazolidinone (S)-15 improved the diaste-
reoselectivity of the minor oxazolidinone (4R,5S)-14 from
34% to 60% de in favour of the corresponding anti-adduct
18 (Scheme 8: entry 6). For these resolutions both the ma-
jor components, oxazolidinones (4R,5S)-14 (in Scheme 8:
entry 7) and oxazolidinones (S)-15 (in Scheme 8: entry 6)
gave reduced levels of diastereoselectivity.
parallel kinetic resolutions25 appear to act independently
of each other in an equal and opposite stereochemical sense
and lead to products with near perfect levels of
diastereocontrol.
4. Experimental
4.1. General
All solvents were distilled before use. All reactions were
carried out under nitrogen using oven-dried glassware.
Flash column chromatography was carried out using
Merck Kieselgel 60 (230–400 mesh). Thin layer chromato-
graphy (TLC) was carried out on commercially available
pre-coated plates (Merck Kieselgel 60F254 silica). Proton
and carbon NMR spectra were recorded on a Bruker 250
and 400 MHz Fourier transform spectrometers using an
internal deuterium lock. Chemical shifts are quoted in parts
per million downfield from tetramethylsilane. Carbon
NMR spectra were recorded with broad proton decou-
pling. Infrared spectra were recorded on a Shimadzu
8300 FTIR spectrometer. Optical rotations were measured
using an automatic AA-10 Optical Activity Ltd polarime-
ter. The levels of D-incorporation were determined by a
combination of mass, proton and carbon NMR spectra.
4.2. 2-Phenylpropanoyl chloride rac-126
We next chose to investigate the resolution of racemic
2-phenylpropanoyl chloride rac-1 using an equimolar
combination of oxazolidinones containing the same sense
of chirality, such as (R)-16 and (R)-17, and (R)-16 and
(4R,5S)-14 to probe their compatibility (Scheme 9). How-
ever, these combinations behaved similarly to their parent
kinetic resolutions (as illustrated in Scheme 4) giving little
to no levels of diastereocontrol (Scheme 9).
2-Phenylpropionic acid 13 (10.0 g, 9.10 ml, 66.5 mmol) was
slowly added to neat thionyl chloride (11.9 g, 7.28 ml,
99.8 mmol) and refluxed at 100 ꢁC for 90 min. The solution
was distilled (using a short path distillation apparatus at
100–105 ꢁC at 17.5 mmHg) to give the corresponding acid
chloride rac-1 (9.64 g, 86%); mmax (film); cmꢀ1 1782
(C@O), dH (270 MHz, CDCl3) 7.36–7.28 (5H, m, 5 · CH;
Ar), 4.11 (1H, q, J 7.1, CH) and 1.59 (3H, d, J 7.1, Me);
dC (100 MHz, CDCl3) 175.9 (C@O), 140.2 (i-C; Ph),
129.9, 129.3 and 129.2 (3 · CH; Ph), 57.9 (CH) and 18.6
(Me) (found M(35Cl), 168.0337; C9H9ClO requires
168.0336).
3. Conclusion
In conclusion, we have a reported an improved method for
the diastereoselective addition of lithiated oxazolidinones to
racemic 2-phenylpropanoyl chloride rac-1 by using a paral-
lel kinetic resolution involving complementary (quasi)-
enantiomeric Evans oxazolidinones [e.g., (4R,5S)-14 and
(S)-15]. We have found that a number of effects, such as
the structural nature of the complementary (quasi)-enantio-
meric oxazolidinones, choice of metal counter-ions and
temperature play an important role of the levels and relative
diastereoselectivity; a lithium counter-ion and low tempera-
ture promotes the formation of the anti-adduct, whereas, a
potassium counter-ion and/or high temperature favours the
syn-adduct. The nearest analogy to this work are the paral-
lel kinetic resolutions reported by Fox,22 Vedejs23 and Da-
vies.24 Fox22 has shown that a combination of quasi-
enantiomeric oxazolidinones can efficiently resolve racemic
anhydrides, whereas, Vedejs has elegantly shown the effi-
cient parallel kinetic resolution of 1-phenylethanol using
two complementary quasi-enantiomeric chlorocarbo-
nates.23 By comparison, Davies has shown the use of two
quasi-enantiomeric lithium amides to resolve racemic
enoates.24 It is particularly noteworthy that these efficient
4.3. (4S)-Isopropyl-3-((2S)-phenylpropionyl)oxazolidin-2-
one anti-5 and (4S)-isopropyl-3-((2R)-phenylpropio-
nyl)oxazolidin-2-one syn-58,17a,b,27,28
n-BuLi (1.55 ml, 2.5 M in hexanes, 3.87 mmol) was added
to a stirred solution of oxazolidinone (S)-4 (0.5 g,
3.87 mmol) in THF at ꢀ78 ꢁC. After stirring for 1 h, a solu-
tion of ( )-2-phenylpropanoyl chloride rac-1 (1.31 g,
7.74 mmol) in THF (5.0 ml) was added. The resulting mix-
ture was stirred for 2 h at ꢀ78 ꢁC. The reaction was
quenched with water (10 ml). The organic layer was ex-
tracted with diethyl ether (2 · 10 ml), dried over MgSO4
and evaporated under reduced pressure to give a separable
mixture of two diastereoisomers (ratio: anti-:syn- 52:48) of
oxazolidinones anti- and syn-5. The residue was purified by
flash column chromatography on silica gel eluting with
light petroleum (bp 40–60 ꢁC)/diethyl ether (1:1) to give
oxazolidinone anti-5 (0.27 g, 27%) as an oil; RF [light petro-
20
leum (bp 40–60 ꢁC)/diethyl ether (1:1)] 0.64; ½aꢁD ¼ þ128:9
20
(c 3.5, CHCl3)30 {lit.11 ½aꢁD ¼ þ100:6 (c 1.11, CHCl3)},

S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
3393
vmax (film); cmꢀ1 1774 (C@O) and 1701 (C@O); dH
(250 MHz; CDCl3) 7.38–7.20 (5H, m, 5 · CH; Ph), 5.15
(1H, q, J 7.0, PhCH), 4.39–4.33 (1H, m, CHN), 4.18–
4.08 (2H, m, CH2O), 2.50–2.38 (1H, m, CH(CH3)2), 1.52
(3H, d, J 7.0, CH3CH), 0.92 (3H, d, J 7.0, CHACHCHB)
(0.95 g, 5.6 mmol), gave after purification by flash column
chromatography eluting with light petroleum (bp 40–
60 ꢁC)/diethyl ether (7:3), a separable diastereoisomeric
mixture (anti-:syn-: ratio 50:50) of oxazolidinones anti-18
(0.24 g, 35%) as a white solid; mp = 89-92 ꢁC; RF [light
3
3
and 0.91 (3H, d, J 6.9, CHACHCHB); dC (62.9 MHz;
petroleum (bp 40–60 ꢁC)/diethyl ether (1:1)] 0.76;
3
3
20
CDCl3) 174.7 (NC@O), 153.6 (OC@O), 140.4 (i-C; Ph),
128.6, 128.2 and 127.2 (3 · CH; Ph), 63.2 (CH2O), 59.1
(CHN), 43.1 (PhCH), 28.6 (CH(CH3)2), 19.7 (CH3), 18.1
(CH3) and 14.8 (CH3CH) (found MH+ 262.1434;
½aꢁD ¼ ꢀ42:7 (c 3, CHCl3);30 mmax (CHCl3); cmꢀ1 1778
(C@O) and 1697 (C@O); dH (250 MHz; CDCl3) 7.44–7.24
(10H, m, 10 · CH; 2 · Ph), 5.49 (1H, d, J 7.1, OCHPh),
5.14 (1H, q, J 7.1, PhCH), 4.68 (1H, m, CHN), 1.51 (3H,
d, J 7.1, CH3CHCO) and 0.94 (3H, d, J 6.6, CH3CHN);
dC (62.9 MHz; CDCl3) 174.5 (NC@O), 152.6 (OC@O),
140.5 (i-C; PhA; PhCHCH3), 133.3 (i-C; PhB; PhCHO),
129.2, 129.1, 128.7, 128.2, 127.3 and 125.6 (6 · CH; PhA
and PhB), 78.7 (OCHPh), 55.5 (CHN), 43.4 (PhCH), 19.3
(CH3) and 14.6 (CH3) (found MH+ 310.1430.
C15H20NO requires 262.1443); m/z 262 (30, MH+), 130
þ
3
(48, MꢀC9H8O) and 105 (100, MꢀC7H11NO3); and the
oxazolidinone syn-5 (0.20 g, 20%); RF [light petroleum
20
(bp 40–60 ꢁC)/diethyl ether (1:1)] 0.43; ½aꢁD ¼ ꢀ19:8 (c
20
3.3, CHCl3)30 {lit.27 ½aꢁD ¼ ꢀ19:2 (c 1.15, CHCl3)}; mmax
(CHCl3); cmꢀ1 1774 (C@O) and 1703 (C@O); dH
(250 MHz; CDCl3) 7.39–7.19 (5H, m, 5 · CH; Ph), 5.14
(1H, q, J 6.9, CH3CHCO), 4.49 (1H, m, CHN), 4.24 (1H,
t, J 8.9, CHAHBO), 4.10 (1H, dd, J 8.9 and 3.5, CHAHBO),
2.24–2.12 (1H, m, CH(CH3)2), 1.47 (3H, d, J 6.9,
CH3CHCO), 0.79 (3H, d, J 7.0, CHACHCHB) and 0.46
C19H20NO3 requires 310.1443); m/z 310 (31%, MH+),
þ
178 (9, MꢀC9H8O) and 105 (100, MꢀC11H11NO3); and
the oxazolidinones syn-18 (0.24 g, 35%) as a white solid;
mp = 121–123 ꢁC; RF [light petroleum (bp 40–60 ꢁC)/
20
diethyl ether (1:1)] 0.63; ½aꢁD ¼ þ105:9 (c 2.6, CHCl3);30
3
3
(3H, d, J 6.9, ACH3CHBCH3); dC (62.9 MHz; CDCl3)
174.5 (NC@O), 153.5 (OC@O), 140.5 (i-C; Ph), 128.6,
128.1 and 127.2 (3 · CH; Ph), 62.9 (CH2O), 58.1 (CHN),
43.3 (PhCH), 27.9 (CH(CH3)2), 18.7 (CH3), 17.8 (CH3)
mmax (CHCl3); cmꢀ1 1774 (C@O) and 1701 (C@O); dH
(250 MHz; CDCl3) 7.40–7.17 (10H, m, 10 · CH; PhA and
PhB), 5.64 (1H, d, J 7.2, OCHPh), 5.08 (1H, q, J 7.1,
PhCH), 4.82 (1H, m, CHN), 1.51 (3H, d, J 7.1,
CH3CHCO) and 0.74 (3H, d, J 6.6, CH3CHN); dC
(62.9 MHz; CDCl3) 174.3 (NC@O), 152.5 (OC@O), 140.3
(i-C; PhA; PhCHCH3), 133.5 (i-C; PhB; PhCHO), 128.9,
128.8, 128.6, 128.1, 127.1 and 125.7 (6 · CH; PhA and
PhB), 78.8 (OCHPh), 54.7 (CHN), 43.6 (PhCH), 19.4
(CH3) and 14.1 (CH3) (found MH+ 310.1460.
and 14.1 (CH3CH) (found MH+ 262.1432; C15H20NO re-
þ
3
quires 262.1443); m/z 262 (30%, MH+), 130 (48,
MꢀC9H8O) and 105 (100, MꢀC7H11NO3).
4.4. Kinetic resolution of 2-phenylpropanoyl chloride rac-1
with oxazolidinone rac-4
C19H20NO3 requires 310.1443); m/z 310 (28%, MH+),
þ
In the same way as oxazolidinone 5, n-BuLi (0.62 ml, 2.5 M
in hexane, 1.55 mmol), oxazolidinone rac-4 (0.2 g,
1.54 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.26 g, 1.54 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-: ra-
tio 50:50) of oxazolidinones anti-5 (0.104 g, 26%) and syn-5
(0.104 g, 26%), which were spectroscopically identical to
those previously obtained.
178 (8, MꢀC9H8O) and 105 (100, MꢀC11H11NO3).
4.7. Kinetic resolution of 2-phenylpropanoyl chloride rac-1
using a racemic oxazolidinone (4R,5S)-14
In the same way as oxazolidinone 5, n-BuLi (0.68 ml, 2.5 M
in hexane, 1.70 mmol), (4RS,5SR)-oxazolidinone rac-14
(0.30 g, 1.69 mmol) and ( )-2-phenylpropanoyl chloride
rac-1 (0.28 g, 1.69 mmol), gave after purification by flash
column chromatography eluting with light petroleum/
diethyl ether (7:3), a separable diastereoisomeric mixture
(anti-:syn-: ratio 50:50) of oxazolidinones anti-18 (0.18 g,
45%) and syn-18 (0.18 g, 23%), which were spectroscopi-
cally identical to those previously obtained.
4.5. Mutual kinetic resolution of 2-phenylpropanoyl chloride
rac-1 with oxazolidinone rac-4
In the same way as oxazolidinone 5, n-BuLi (0.62 ml, 2.5 M
in hexane, 1.55 mmol), oxazolidinone rac-4 (0.2 g,
1.54 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.26 g, 1.54 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3),
a
separable diastereoisomeric mixture (anti-:
4.8. Mutual kinetic resolution of 2-phenylpropanoyl chloride
rac-1 using a racemic oxazolidinone (4R,5S)-14
syn-: ratio 70:30) of oxazolidinones anti-5 (0.17 g, 42%)
and syn-5 (72 mg, 18%), which were spectroscopically
identical to those previously obtained.
In the same way as oxazolidinone 5, n-BuLi (0.68 ml, 2.5 M
in hexane, 1.70 mmol), (4RS,5SR)-oxazolidinone rac-14
(0.30 g, 1.69 mmol) and ( )-2-phenylpropanoyl chloride
rac-1 (0.28 g, 1.69 mmol), gave after purification by flash
column chromatography eluting with light petroleum/
diethyl ether (7:3), a separable diastereoisomeric mixture
(anti-:syn-: ratio 67:33) of oxazolidinones anti-18 (0.23 g,
45%) and syn-18 (0.12 g, 23%), which were spectroscopi-
cally identical to those previously obtained.
4.6. (4R,5S)-4-Methyl-5-phenyl-3-(2R-phenylpropio-
nyl)oxazolidin-2-one anti-18 and (4R,5S)-4-methyl-5-phenyl-
3-(2S-phenylpropionyl)oxazolidin-2-one syn-18
In the same way as oxazolidinone 5, n-BuLi (0.91 ml, 2.5 M
in hexane, 2.28 mmol), oxazolidinone (4R,5S)-14 (0.4 g,
2.28 mmol) and ( )-2-phenylpropanoyl chloride rac-1

3394
S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
4.9. (4S)-Benzyl-3-((2S)-phenylpropionyl)oxazolidine-2-one
anti-19 and (4S)-benzyl-3-((2R)-phenylpropionyl)oxazoli-
dine-2-one syn-1911,27
1.13 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.19 g, 1.13 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-: ra-
tio 50:50) of oxazolidinones anti-19 (0.122 g, 35%) and syn-
19 (0.122 g, 35%), which were spectroscopically identical to
those previously obtained.
In the same way as oxazolidinone 5, n-BuLi (0.45 ml, 2.5 M
in hexane, 1.13 mmol), oxazolidinone (S)-15 (0.2 g,
1.13 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.38 g, 2.26 mmol), gave after purification by flash column
chromatography eluting with light petroleum (bp 40–
60 ꢁC)/diethyl ether (7:3), a separable diastereoisomeric
mixture (anti-:syn-: ratio 52:48) of oxazolidinones anti-19
4.12. Synthesis of ethyl (4S,2R)-2-oxa-3-(20-phenylpropio-
nyl)oxazolidin-4-carboxylate anti-20 and ethyl (4S,2S)-2-
oxa-3-(20-phenylpropionyl)oxazolidin-4-carboxylate syn-20
(0.12 g, 35%) as an oil; RF [light petroleum (bp 40–60 ꢁC)/
20
diethyl ether (1:1)] 0.66; ½aꢁD ¼ þ130:4 (c 1.8, CHCl3)
20
{lit.11 ½aꢁD ¼ þ107:1 (c 1.01, CHCl3)}; mmax (CHCl3);
In the same way as oxazolidinone 5, n-BuLi (2.01 ml, 2.5 M
in hexane, 5.03 mmol), oxazolidinone (S)-16 (0.8 g,
5.03 mmol) and ( )-2-phenyl propanoyl chloride rac-1
(1.69 g, 10.1 mmol), gave a mixture of two diastereoiso-
mers [ratio 50:50: anti-:syn-] of oxazolidinones 20. The
crude residue was purified by flash column chromatogra-
phy on silica gel eluting with light petroleum (bp 40–
60 ꢁC)/diethyl ether (7:3) the (S,R)-oxazolidinone anti-20
cmꢀ1 1780 (C@O) and 1699 (C@O); dH (270 MHz; CDCl3)
7.39–7.21 (10H, m, 10 · CH; 2 · Ph), 5.12 (1H, q, J 7.0,
PhCH), 4.61–4.54 (1H, m, CHN), 4.12–4.10 (2H, m,
CH2O), 3.35 (1H, dd, J 13.1 and 3.2, CHAHBPh), 2.80
(1H, dd, J 13.1 and 9.8, CHAHBPh) and 1.55 (3H, d, J
7.0, CH3CH); dC (100 MHz; CDCl3) 174.7 (NC@O), 152.9
(OC@O), 140.3 (i-C; PhA), 135.4 (i-C; PhB), 129.5, 129.0,
128.7, 128.1, 127.4 and 127.3 (6 · CH; PhA and PhB), 65.9
(CH2O), 55.8 (CHN), 43.2 (PhCH), 38.0 (CH2Ph) and
(0.51 g, 35%) as an oil; RF [light petroleum (bp 40–
20
60 ꢁC)/diethyl ether (1:1)] 0.42; ½aꢁD ¼ ꢀ135:8 (c 4.5,
19.5 (CH3) (found MH+ 310.1442. C19H20NO requires
CHCl3); mmax (CHCl3); cmꢀ1 1794 (C@O), 1747 (C@O)
and 1705 (C@O); dH (270 MHz; CDCl3) 7.33–7.20 (5H,
m, 5 · CH; Ph), 5.10 (1H, q, J 7.0, PhCH), 4.77 (1H, dd,
J 9.4 and 3.7, CHN), 4.38 (1H, t, J 9.4, CHAHBO), 4.31–
4.21 (3H, m, CHAHBO and CH2CH3), 1.50 (3H, d, J 7.0,
CH3CH) and 1.30 (3H, t, J 7.2, CH3CH2); dC (62.9 MHz;
CDCl3) 174.5 (NC@O), 168.7 (CC@O), 152.1 (OC@O),
140.0 (i-C; Ph), 128.7, 128.3 and 127.4 (3 · CH; Ph), 64.3
(CH2O), 62.6 (CH2O), 55.9 (CHN), 43.0 (PhCH), 19.3
(CH3CH) and 14.1 (CH3CH2) (found MH+, 292.1195;
þ
3
310.1443); m/z 310 (80%, MH+), 178 (18, MꢀC9H8O),
132 (100, MꢀC10H12NO2) and 105 (18, MꢀC11H11NO3);
and the oxazolidinone syn-19 (0.12 g, 35%) as a viscous
oil; RF [light petroleum (bp 40–60 ꢁC)/diethyl ether
20
20
(1:1)] 0.43; ½aꢁD ¼ þ2:8 (c 5.5, CHCl3); {lit.31 ½aꢁD ¼ þ2:2
20
(c 2.8, CHCl3)} {lit.11 ½aꢁD ¼ þ16:1 (c 0.96, CHCl3)}; mmax
(CHCl3); cmꢀ1 1775 (C@O) and 1700 (C@O); dH
(270 MHz; CDCl3) 7.45–6.94 (10H, m, 10 · CH; PhA and
PhB), 5.11 (1H, q, J 6.9, PhCH), 4.79–4.70 (1H, m, CHN),
4.18 (1H, t, J 8.5, CHAHBO), 4.07 (1H, dd J 8.5 and 3.2,
CHAHBO), 3.08 (1H, dd J 13.5 and 3.2, CHAHBPh), 2.58
(1H, dd, J 13.5 and 8.8, CHAHBPh) and 1.52 (3H, d, J
6.9, CH3CH); dC (100 MHz; CDCl3) 174.5 (NC@O), 153.0
(OC@O), 140.2 (i-C; PhA), 135.0 (i-C; PhB), 129.4, 128.8,
128.6, 128.3, 127.3 and 127.2 (6 · CH; PhA and PhB), 65.8
(CH2O), 54.9 (CHN), 43.2 (PhCH), 37.4 (CH2) and 19.2
þ
C15H18NO5 requires 292.1185) and the (S,S)-oxazolidi-
none syn-20 (0.49 g, 34%) as a white powder; mp = 97-
99 ꢁC; RF [light petroleum (bp 40–60 ꢁC)/diethyl ether
20
(1:1)] 0.30; ½aꢁD ¼ þ17:2 (c 2.2, CHCl3); mmax (CHCl3);
cmꢀ1 1793 (C@O), 1747 (C@O) and 1705 (C@O); dH
(270 MHz; CDCl3) 7.40–7.20 (5H, m, 5 · CH; Ph), 5.03
(1H, q, J 7.0, PhCH), 4.94 (1H, dd, J 9.3 and 4.9, CHN),
4.52 (1H, t, J 9.3, CHAHBO), 4.23 (1H, dd, J 9.3 and 4.9,
CHAHBO), 4.11 (2H, q, J 7.2, CH2CH3), 1.48 (3H, d, J
7.0, CH3CH) and 1.11 (3H, t, J 7.2, CH3CH2); dC
(62.9 MHz; CDCl3) 174.3 (NC@O), 168.1 (CC@O), 152.0
(OC@O), 139.8 (i-C; Ph), 128.5, 128.2 and 127.2 (3 · CH;
Ph), 64.3 (CH2O), 62.4 (CH2O), 55.7 (CHN), 43.2 (PhCH),
19.4 (CH3) and 13.9 (CH3) (found MH+, 292.1195;
(CH3) (found MH+ 310.1438. C19H20NO
requires
þ
3
310.1443); m/z 310 (80%, MH+), 178 (15, MꢀC9H8O),
132 (100, MꢀC10H12NO2) and 105 (15, MꢀC11H11NO3).
4.10. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 using a racemic lithiated oxazolidinone rac-15
þ
In the same way as oxazolidinone 5, n-BuLi (0.45 ml, 2.5 M
in hexane, 1.12 mmol), oxazolidinone rac-15 (0.20 g,
1.13 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.19 g, 1.13 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-: ra-
tio 59:41) of oxazolidinones anti-19 (0.126 g, 36%) and syn-
19 (91 mg, 26%), which were spectroscopically identical to
those previously obtained.
C15H18NO5 requires 292.1185).
4.13. Kinetic resolution of 2-phenylpropanoyl chloride rac-1
with oxazolidinone rac-16
In the same way as oxazolidinone 5, n-BuLi (0.50 ml, 2.5 M
in hexane, 1.25 mmol), oxazolidinone rac-4 (0.2 g,
1.25 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.21 g, 1.25 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-: ra-
tio 50:50) of oxazolidinones anti-20 (0.105 g, 29%) and syn-
20 (0.109 g, 30%), which were spectroscopically identical to
those previously obtained.
4.11. Kinetic resolution of 2-phenylpropanoyl chloride
rac-1 using a racemic lithiated oxazolidinone rac-15
In the same way as oxazolidinone 5, n-BuLi (0.45 ml, 2.5 M
in hexane, 1.12 mmol), oxazolidinone rac-15 (0.20 g,

S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
3395
4.14. Mutual kinetic resolution of 2-phenylpropanoyl chlo-
ride rac-1 with oxazolidinone rac-16
ratio 50:50) of oxazolidinones anti-5 (0.122 g, 34%) and
syn-5 (0.125 g, 35%), which were spectroscopically identical
to those previously obtained.
In the same way as oxazolidinone 5, n-BuLi (0.50 ml, 2.5 M
in hexane, 1.25 mmol), oxazolidinone rac-4 (0.2 g,
1.25 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.21 g, 1.25 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-: ra-
tio 59:41) of oxazolidinones anti-20 (0.128 g, 35%) and syn-
20 (87 mg, 24%), which were spectroscopically identical to
those previously obtained.
4.17. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 with oxazolidinone rac-21
In the same way as oxazolidinone 5, n-BuLi (0.62 ml, 2.5 M
in hexane, 1.55 mmol), oxazolidinone rac-4 (0.2 g,
1.54 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.26 g, 1.54 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-: ra-
tio 56:44) of oxazolidinones anti-5 (0.116 g, 32%) and syn-5
(93 mg, 26%), which were spectroscopically identical to
those previously obtained.
4.15. Synthesis of (4R,2R)-4-phenyl-3-(20-phenylpropio-
nyl)oxazolidin-2-one anti-21 and (4R,2S)-4-phenyl-3-(20-
phenylpropionyl)oxazolidin-2-one syn-2111,17a,b,27,28
In the same way as oxazolidinone 5, n-BuLi (0.49 ml, 2.5 M
in hexane, 1.23 mmol), oxazolidinone (R)-17 (0.2 g,
1.23 mmol) and ( )-2-phenyl propanoyl chloride rac-1
(0.41 g, 2.45 mmol), gave a mixture of two diastereoiso-
mers [ratio (57/43:anti-/syn-)] of oxazolidinone 21. The
crude residue was purified by flash column chromatogra-
phy on silica gel eluting with light petroleum (bp 40–
60 ꢁC)/ether (7:3) the (R,R)-oxazolidinone anti-21 (0.14 g,
4.18. Temperature study
4.18.1. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 with oxazolidinone rac-4 at ꢀ97 ꢁC. In the
same way as oxazolidinone 5, n-BuLi (0.62 ml, 2.5 M in
hexane, 1.55 mmol), oxazolidinone rac-4 (0.2 g, 1.54 mmol)
and ( )-2-phenylpropanoyl chloride rac-1 (0.26 g,
1.54 mmol) at ꢀ97 ꢁC, gave after purification by flash col-
umn chromatography eluting with light petroleum/diethyl
ether (7:3), a separable diastereoisomeric mixture (anti-:
syn-: ratio 70:30) of oxazolidinones anti- and syn-5
(0.16 g, 40%), which were spectroscopically identical to
those previously obtained.
38%) as a white solid; mp = 158–160 ꢁC; RF [light petro-
20
leum (bp 40–60 ꢁC)/ether (1:1)] 0.58; ½aꢁD ¼ ꢀ180:5 (c 1.52,
20
CHCl3) {lit.29 ½aꢁD ¼ ꢀ163:2 (c 0.1, CHCl3)}; mmax
(CHCl3); cmꢀ1 1780 (C@O) and 1700 (C@O); dH
(270 MHz; CDCl3) 7.39–7.26 (10H, m, 10 · CH; 2 · Ph),
5.32 (1H, dd, J 8.8 and 3.2, CHN), 5.11 (1H, q, J 7.2,
PhCH), 4.55 (1H, t, J 8.8, CHAHBO), 4.21 (1H, dd, J 8.8
and 3.2, CHAHBO) and 1.40 (3H, d, J 7.2, CH3CH); dC
(62.9 MHz; CDCl3) 174.1 (NC@O), 152.9 (OC@O), 140.2
(i-C; PhA), 139.4 (i-C; PhB), 129.3, 128.7, 128.6, 128.2,
127.3 and 125.8 (6 · CH; PhA and PhB), 69.7 (CH2O),
58.1 (CHN), 43.2 (PhCH) and 19.4 (CH3) (found MH+,
4.18.2. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 with oxazolidinone rac-4 at ꢀ29 ꢁC. In the
same way as oxazolidinone 5, n-BuLi (0.62 ml, 2.5 M in
hexane, 1.55 mmol), oxazolidinone rac-4 (0.2 g, 1.54 mmol)
and ( )-2-phenylpropanoyl chloride rac-1 (0.26 g,
1.54 mmol) at ꢀ29 ꢁC, gave after purification by flash col-
umn chromatography eluting with light petroleum/diethyl
ether (7:3), a separable diastereoisomeric mixture (anti-
:syn-: ratio 57:43) of oxazolidinones anti- and syn-5
(0.26 g, 65%), which were spectroscopically identical to
those previously obtained.
þ
296.1282; C18H18NO3 requires 296.1287); and the (R,S)-
oxazolidinone syn-21 (0.12 g, 33%) as a white solid;
mp = 140–142 ꢁC; RF [light petroleum (bp 40–60 ꢁC)/
ether (1:1)] 0.42; mmax (CHCl3); cmꢀ1 1778 (C@O) and
20
20
1701 (C@O); ½aꢁD ¼ þ88:5 (c 4.0, CHCl3); {lit.29 ½aꢁD
¼
þ143:4 (c 0.5 CHCl3)}; dH (270 MHz; CDCl3) 7.29–7.21
(10H, m, 10 · CH; 2 · Ph), 5.45 (1H, dd, J 9.0 and 5.1,
CHN), 5.09 (1H, q, J 6.9, PhCH), 4.63 (1H, t, J 9.0,
CHAHBO), 4.08 (1H, dd, J 9.0 and 5.1, CHAHBO) and
1.39 (3H, d, J 6.9, CH3CH); dC (62.9 MHz; CDCl3) 173.7
(NC@O), 153.2 (OC@O), 139.9 (i-C; PhA), 138.3 (i-C;
PhB), 128.9, 128.7, 128.5, 128.2, 127.1 and 125.9 (6 · CH;
PhA and PhB), 69.6 (CH2O), 57.9 (CHN), 43.9 (PhCH)
4.18.3. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 with oxazolidinone rac-4 at 0 ꢁC. In the
same way as oxazolidinone 5, n-BuLi (0.62 ml, 2.5 M in
hexane, 1.55 mmol), oxazolidinone rac-4 (0.2 g, 1.54 mmol)
and ( )-2-phenylpropanoyl chloride rac-1 (0.26 g,
1.54 mmol) at 0 ꢁC, gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-: ra-
tio 45:55) of oxazolidinones anti- and syn-5 (0.21 g, 52%),
which were spectroscopically identical to those previously
obtained.
and 18.6 (CH3) (found MH+, 296.1286; C15H18NO re-
þ
3
quires 296.1287).
4.16. Kinetic resolution of 2-phenylpropanoyl chloride rac-1
with oxazolidinone rac-21
4.18.4. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 with oxazolidinone rac-4 at 25 ꢁC. In the
same way as oxazolidinone 5, n-BuLi (0.62 ml, 2.5 M in
hexane, 1.55 mmol), oxazolidinone rac-4 (0.2 g, 1.54 mmol)
and ( )-2-phenylpropanoyl chloride rac-1 (0.26 g,
1.54 mmol) at 25 ꢁC, gave after purification by flash col-
umn chromatography eluting with light petroleum/diethyl
In the same way as oxazolidinone 5, n-BuLi (0.48 ml, 2.5 M
in hexane, 1.22 mmol), oxazolidinone (R)-17 (0.2 g,
1.22 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.20 g, 1.22 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-:

3396
S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
ether (7:3), a separable diastereoisomeric mixture (anti-
:syn-: ratio 33:67) of oxazolidinones anti- and syn-5
(0.20 g, 49%), which were spectroscopically identical to
those previously obtained.
noyl chloride (S)-1 (0.13 g, 0.77 mmol) at ꢀ78 ꢁC, gave
after purification by flash column chromatography eluting
with light petroleum/diethyl ether (7:3) the diastereoiso-
merically (S,S)-oxazolidinone anti-5 (80 mg, 40%) as an
oil, which was spectroscopically identical to that previously
obtained. The presence of a single diastereoisomeric adduct
was determined by 400 MHz 1H NMR spectroscopy of the
crude and purified samples.
4.18.5. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 with oxazolidinone rac-4 at 50 ꢁC. In the
same way as oxazolidinone 5, n-BuLi (0.62 ml, 2.5 M in
hexane, 1.55 mmol), oxazolidinone rac-4 (0.2 g, 1.54 mmol)
and ( )-2-phenylpropanoyl chloride rac-1 (0.26 g,
1.54 mmol) at 50 ꢁC, gave after purification by flash col-
umn chromatography eluting with light petroleum/diethyl
ether (7:3), a separable diastereoisomeric mixture (anti-:
syn-: ratio 33:67) of oxazolidinones anti- and syn-5
(0.20 g, 49%), which were spectroscopically identical to
those previously obtained.
4.20.2. Addition of propanoyl chloride (S)-1 (derived from
enantiomerically pure 2-phenylpropanoic acid) to the oxazo-
lidinone (R)-4 at ꢀ78 ꢁC. In the same way as oxazolidi-
none 5, n-BuLi (0.31 ml, 2.5 M in hexane, 0.77 mmol),
oxazolidinone (R)-4 (0.1 g, 0.77 mmol) and 2-phenylpropa-
noyl chloride (S)-1 (0.13 g, 0.77 mmol) at ꢀ78 ꢁC, gave
after purification by flash column chromatography eluting
with light petroleum/diethyl ether (7:3) the diastereoiso-
merically (R,S)-oxazolidinone syn-5 (60 mg, 30%) as an
oil, which was spectroscopically identical to that previously
obtained. The presence of a single diastereoisomeric adduct
4.19. Deprotonation with metal amides
4.19.1. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 with oxazolidinone rac-4 using LiHMDS. In
the same way as oxazolidinone 5, LiHMDS (1.55 ml, 1 M
in THF, 1.55 mmol), oxazolidinone rac-4 (0.2 g,
1.54 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.26 g, 1.54 mmol) at 50 ꢁC, gave after purification by
flash column chromatography eluting with light petro-
leum/diethyl ether (7:3), a separable diastereoisomeric mix-
ture (anti-:syn-: ratio 64:36) of oxazolidinones anti- and
syn-5 (0.28 g, 70%), which were spectroscopically identical
to those previously obtained.
1
was confirmed by 400 MHz H NMR spectroscopy of the
crude and purified samples.
4.20.3. Addition of propanoyl chloride (S)-1 (derived from
enantiomerically pure 2-phenylpropanoic acid) to the oxazo-
lidinone (S)-4 at 25 ꢁC. In the same way as oxazolidinone
5, n-BuLi (0.31 ml, 2.5 M in hexane, 0.77 mmol), oxazolid-
inone (S)-4 (0.1 g, 0.77 mmol) and 2-phenylpropanoyl
chloride (S)-1 (0.13 g, 0.77 mmol) at 25 ꢁC, gave after puri-
fication by flash column chromatography eluting with light
petroleum/diethyl ether (7:3) the diastereoisomerically
(S,S)-oxazolidinone anti-5 (59 mg, 25%) as an oil, which
was spectroscopically identical to that previously obtained.
The presence of a single diastereoisomeric adduct was con-
4.19.2. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 with oxazolidinone rac-4 using NaH-
MDS. In the same way as oxazolidinone 5, NaHMDS
(0.77 ml, 2 M in THF, 1.55 mmol), oxazolidinone rac-4
(0.2 g, 1.54 mmol) and ( )-2-phenylpropanoyl chloride
rac-1 (0.26 g, 1.54 mmol) at 50 ꢁC, gave after purification
by flash column chromatography eluting with light petro-
leum/diethyl ether (7:3), a separable diastereoisomeric mix-
ture (anti-:syn-: ratio 34:66) of oxazolidinones anti- and
syn-5 (0.28 g, 70%), which were spectroscopically identical
to those previously obtained.
1
firmed by 400 MHz H NMR spectroscopy of the crude
and purified samples.
4.20.4. Addition of propanoyl chloride (S)-1 (derived from
enantiomerically pure 2-phenylpropanoic acid) to the oxazo-
lidinone (R)-4 at 25 ꢁC. In the same way as oxazolidinone
5, n-BuLi (0.31 ml, 2.5 M in hexane, 0.77 mmol), oxazolid-
inone (R)-4 (0.1 g, 0.77 mmol) and 2-phenylpropanoyl
chloride (S)-1 (0.13 g, 0.77 mmol) at 25 ꢁC, gave after puri-
fication by flash column chromatography eluting with light
petroleum/diethyl ether (7:3), the diastereoisomerically
(R,S)-oxazolidinone syn-5 (62 mg, 31%) as an oil, which
was spectroscopically identical to that previously obtained.
The presence of a single diastereoisomeric adduct was con-
4.19.3. Mutual kinetic resolution of 2-phenylpropanoyl
chloride rac-1 with oxazolidinone rac-4 using KHMDS. In
the same way as oxazolidinone 5, KHMDS (3.1 ml, 0.5 M
in THF, 1.55 mmol), oxazolidinone rac-4 (0.2 g,
1.54 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.26 g, 1.54 mmol) at 50 ꢁC, gave after purification by
flash column chromatography eluting with light petro-
leum/diethyl ether (7:3), a separable diastereoisomeric mix-
ture (anti-:syn-: ratio 38:62) of oxazolidinones anti- and
syn-5 (0.23 g, 70%), which were spectroscopically identical
to those previously obtained.
1
firmed by 400 MHz H NMR spectroscopy of the crude
and purified samples.
4.21. Isotope study
4.21.1. Mutual kinetic resolution of 2-deuterio-2-phenyl-
propanoyl chloride rac-[D1]-1 with oxazolidinone rac-4. In
the same way as oxazolidinone 5, n-BuLi (0.62 ml, 2.5 M in
hexane, 1.55 mmol), oxazolidinone rac-4 (0.2 g, 1.54 mmol)
and ( )-2-deuterio-2-phenylpropanoyl chloride rac-[D1]-1
([D]:[H] = 94:6—determined by 1H NMR spectroscopy
and low resolution mass spectrometry) (0.26 g, 1.54 mmol)
at 50 ꢁC, gave after purification by flash column chroma-
tography eluting with light petroleum/diethyl ether (7:3),
4.20. Configurational stability study
4.20.1. Addition of propanoyl chloride (S)-1 (derived from
enantiomerically pure 2-phenylpropanoic acid) to the oxazo-
lidinone (S)-4 at ꢀ78 ꢁC. In the same way as oxazolidi-
none 5, n-BuLi (0.31 ml, 2.5 M in hexane, 0.77 mmol),
oxazolidinone (S)-4 (0.1 g, 0.77 mmol) and 2-phenylpropa-

S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
3397
a separable diastereoisomeric mixture (anti-:syn-: ratio
65:35) of oxazolidinones anti-[D1]-5 ([D]:[H] = 95:5)
(0.10 g, 25%) as a viscous oil; RF [light petroleum (40–
60 ꢁC)/diethyl ether (1:1)] 0.57; mmax (CH2Cl2); cmꢀ1 2306
(br, C–D), 1779 (C@O) and 1698 (C@O); dH (270 MHz;
CDCl3) 7.39–7.15 (5H, m, 5 · CH; Ph), 435 (1H, m,
CHN), 4.16–4.08 (2H, m, CH2O), 2.43 (1H, m, CH(CH3)2),
1.50 (3H, s, CDCH3), 0.91 (3H, d, J 6.9, CHCHACHB) and
32%) (derived from (S)-15), which were spectroscopically
identical to those obtained previously.
4.22.3. Parallel kinetic resolution of 2-phenylpropanoyl
chloride rac-1 using a quasi-enantiomeric combination of
oxazolidinones (4R,5S)-14 and (S)-15 (relative ratio
3:1). In the same way as oxazolidinone 5, n-BuLi
(0.61 ml, 2.5 M in hexane, 1.52 mmol), oxazolidinone
(4R,5S)-14 (0.2 g, 1.13 mmol) and (S)-15 (66 mg,
0.38 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.25 g, 1.50 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-: ra-
tio 64:36) of oxazolidinones anti-18 (0.11 g, 32%) and syn-
18 (66 mg, 19%) (derived from (4R,5S)-14) and a separable
diastereoisomeric mixture (anti-:syn-: ratio 78:22) of oxazo-
lidinones anti-19 (61 mg, 52%) and syn-19 (16 mg, 13%)
(derived from (S)-15), which were spectroscopically identi-
cal to that previously obtained.
3
3
B
0.90 (3H, d, J 6.9, CHCH3ACH3 ); dC (100 MHz; CDCl3)
173.6 (NC@O), 152.6 (OC@O), 139.1 (i-C; Ph), 127.6,
127.2 and 126.2 (3 · CH; Ph), 62.0 (CH2O), 57.9 (CHN),
1
41.6 (1 C, t, JC,D 20.3, PhCD), 27.4 (CH(CH3)2), 18.5
(CH3), 16.9 (þCH3) and 13.6 (CH3) (found M+, 262.1422;
C15H18DNO3
requires 262.1427); and syn-[D1]-5
([D]:[H] = 95:5) (0.18 g, 44%); RF [light petroleum (40–
60 ꢁC)/diethyl ether (1:1)] 0.50; mp 50–53 ꢁC; mmax
(CH2Cl2); cmꢀ1 2306 (br, C–D), 1778 (C@O) and 1698
(C@O); dH (270 MHz; CDCl3) 7.39–7.17 (5H, m, 5 · CH;
Ph), 4.51–4.45 (1H, m, CHN), 4.23 (1H, t, J 8.9, CHAH-
BO), 4.09 (1H, dd, J 8.9 and 3.6, CHAHBO), 2.16 (1H, m,
CH(CH3)2), 1.45 (3H, s, CDCH3), 0.80 (3H, d, J 6.9,
CHCHACHB) and 0.45 (3H, d, J 6.9, CHCHACHB); dC
4.22.4. Parallel kinetic resolution of 2-phenylpropanoyl
chloride rac-1 using a quasi-enantiomeric combination of
oxazolidinones and (S)-4 and (4R,5S)-14 (ratio 1:1). In the
same way as oxazolidinone 5, n-BuLi (0.45 ml, 2.5 M in
hexane, 1.12 mmol), oxazolidinone (S)-4 (72 mg,
0.56 mmol) and (4R,5S)-14 (0.1 g, 0.56 mmol) and ( )-2-
phenylpropanoyl chloride rac-1 (0.19 g, 1.13 mmol), gave
after purification by flash column chromatography eluting
with light petroleum/diethyl ether (7:3), a separable diaste-
reoisomeric mixture (anti-:syn-: ratio 55:45) of oxazolidi-
nones anti-5 (50 mg, 34%) and syn-5 (41 mg, 28%)
[derived from (S)-4], and a separable diastereoisomeric
mixture (anti-:syn-: ratio 55:45) of oxazolidinones anti-18
(69 mg, 40%) and syn-18 (57 mg, 33%) [derived from
(4R,5S)-14], which were spectroscopically identical to those
obtained previously.
3
3
3
3
(100 MHz; CDCl3) 174.5 (NC@O), 153.5 (OC@O), 140.4
(i-C; Ph), 128.6, 128.0 and 127.3 (3 · CH; Ph), 62.9
1
(CH2O), 58.2 (CHN), 43.0 (1 C, t, JC,D 20.3, PhCD),
29.7 (CH(CH3)2), 18.6 (CH3), 17.8 (CH3) and 14.0 (CH3)
(found MH+, 263.1498; C15H19DNO requires 263.1505).
þ
3
4.22. Parallel kinetic resolutions
4.22.1. Parallel kinetic resolution of 2-phenylpropanoyl
chloride rac-1 using a quasi-enantiomeric combination of
oxazolidinones (4R,5S)-14 and (S)-15 (ratio 1:1). In the
same way as oxazolidinone 5, n-BuLi (0.45 ml, 2.5 M in
hexane, 1.12 mmol), oxazolidinone (4R,5S)-14 (0.1 g,
0.56 mmol) and (S)-15 (0.1 g, 0.56 mmol) and ( )-2-phe-
nylpropanoyl chloride rac-1 (0.19 g, 1.13 mmol), gave after
purification by flash column chromatography eluting with
light petroleum/diethyl ether (7:3), a separable diastereo-
isomeric mixture (anti-:syn-: ratio 67:33) of oxazolidinones
anti-18 (68 mg, 39%) and syn-18 (33 mg, 19%) [derived
from (4R,5S)-14] and a separable diastereoisomeric mix-
ture (anti-:syn-: ratio 72:28) of oxazolidinones anti-19
(74 mg, 44%) and syn-19 (26 mg, 14%) [derived from
(S)-15], which were spectroscopically identical to those
obtained previously.
4.22.5. Parallel kinetic resolution of 2-phenylpropanoyl
chloride rac-1 using a quasi-enantiomeric combination of
oxazolidinones (S)-4 and (R)-17 (ratio 1:1). In the same
way as oxazolidinone 5, n-BuLi (0.48 ml, 2.5 M in hexane,
1.22 mmol), oxazolidinone (S)-4 (78 mg, 0.61 mmol) and
(R)-17 (0.1 g, 0.61 mmol), and ( )-2-phenylpropanoyl
chloride rac-1 (0.21 g, 1.22 mmol), gave after purification
by flash column chromatography eluting with light petro-
leum/diethyl ether (7:3), a separable diastereoisomeric mix-
ture (anti-:syn-: ratio 50:50) of oxazolidinones anti-5
(44 mg, 28%) and syn-5 (44 mg, 28%) [derived from (S)-4]
and a separable diastereoisomeric mixture (anti-:syn-: ratio
56:44) of oxazolidinones anti-21 (48 mg, 27%) and syn-21
(38 mg, 21%) [derived from (R)-17], which were spectro-
scopically identical to those obtained previously.
4.22.2. Parallel kinetic resolution of 2-phenylpropanoyl
chloride rac-1 using a quasi-enantiomeric combination of
oxazolidinones (4R,5S)-14 and (S)-15 (relative ratio
1:3). In the same way as oxazolidinone 5, n-BuLi
(0.61 ml, 2.5 M in hexane, 1.52 mmol), oxazolidinone
(4R,5S)-14 (66 mg, 0.38 mmol) and (S)-15 (0.2 g,
1.13 mmol) and ( )-2-phenylpropanoyl chloride rac-1
(0.25 g, 1.50 mmol), gave after purification by flash column
chromatography eluting with light petroleum/diethyl ether
(7:3), a separable diastereoisomeric mixture (anti-:syn-:
ratio 80:20) of oxazolidinones anti-18 (64 mg, 55%) and
syn-18 (16 mg, 14%) (derived from (4R,5S)-14) and a sepa-
rable diastereoisomeric mixture (anti-:syn-: ratio 54:46) of
oxazolidinones anti-19 (0.14 g, 41%) and syn-19 (0.11 g,
4.22.6. Parallel kinetic resolution of 2-phenylpropanoyl
chloride rac-1 using a quasi-enantiomeric combination of
oxazolidinones (S)-15 and (R)-17 (ratio 1:1). In the same
way as oxazolidinone 5, n-BuLi (0.45 ml, 2.5 M in hexane,
1.12 mmol), oxazolidinone (S)-15 (0.1 g, 0.56 mmol) and
(R)-17 (91.4 g, 0.56 mmol), and ( )-2-phenylpropanoyl
chloride rac-1 (0.19 g, 1.13 mmol), gave after purification
by flash column chromatography eluting with light petro-
leum/diethyl ether (7:3), a separable diastereoisomeric mix-

3398
S. Chavda et al. / Tetrahedron: Asymmetry 17 (2006) 3386–3399
ture (anti-:syn-: ratio 50:50) of oxazolidinones anti-19
(50 mg, 29%) and syn-19 (50 mg, 29%) [derived from (S)-
15] and a separable diastereoisomeric mixture (anti-:syn-:
ratio 50:50) of oxazolidinones anti-21 (48 mg, 29%) and
syn-21 (48 mg, 29%) [derived from (R)-17], which were
spectroscopically identical to those obtained previously.
References
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4.23.1. (ꢀ)-2-Phenylpropionic acid (R)-13. Lithium
hydroxide monohydrate (27 mg, 0.65 mmol) was slowly
added to a stirred solution of oxazolidinone syn-5 (83 mg,
0.32 mmol) and hydrogen peroxide (22 mg, 0.65 mmol,
30%/w) in THF/water (1:1; 5 ml). The reaction mixture
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was quenched with water (10 ml) and extracted with
dichloromethane (3 · 10 ml). The combined organic layers
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(39 mg, 95%) as a white solid. The aqueous phase was acid-
ified using HCl (3 M HCl) until the pH = 3, and extracted
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20
(47.5 mg, 99%) as an oil; ½aꢁD ¼ ꢀ71:2 (c 0.66, CHCl3),
20
{lit.19 ½aꢁD ¼ ꢀ72:0g; mmax (CHCl3); cmꢀ1 1706 (C@O);
RF [light petroleum (bp 40–60 ꢁC)/diethyl ether (1:9)] 0.5;
dH (250 MHz; CDCl3) 7.45–6.98 (5H, m, 5 · CH; Ph),
3.75 (1H, q, J 7.2, PhCH) and 1.5 (3H, d, J 7.2, CH3CH);
dC (67.9 MHz; CDCl3) 181.4 (C@O), 139.9 (i-C; Ph), 128.9,
127.8 and 127.6 (3 · CH; Ph), 45.6 (PhCH) and 18.3 (CH3)
(found MH+ 151.0750. C9H11NO
requires 151.0759);
þ
2
m/z 151 (25%, MH+) and 105 (100, MꢀCH2O2).
4.23.2. (+)-2-Phenylpropionic acid (S)-13. In the same
way as oxazolidinone syn-5, oxazolidinone anti-5 (83 mg,
0.32 mmol), lithium hydroxide monohydrate (27.1 mg,
0.65 mmol) and hydrogen peroxide (22 mg, 0.65 mmol,
30%/w), gave after extraction the recovered oxazolidinone
(S)-4 (39 mg, 95%) as a white solid; and (+)-2-phenyl-
propionic acid (S)-13 (47.5 mg, 99%) as an oil; RF
[light petroleum (bp 40–60 ꢁC)/diethyl ether (1:9)] 0.5;
20
20
½aꢁD ¼ þ71:5 (c 0.64, CHCl3), {lit.19 ½aꢁD ¼ þ72:0g; mmax
(CHCl3); cmꢀ1 1706 (C@O); dH (270 MHz; CDCl3) 7.45–
6.98 (5H, m, 5 · CH; Ph), 3.75 (1H, q, J 7.2, PhCH) and
1.5 (3H, d, J 7.2, CH3CH); dC (67.9 MHz; CDCl3) 181.4
(C@O), 139.9 (i-C; Ph), 128.9, 127.8 and 127.6 (3 · CH;
Ph), 45.6 (þPhCH) and 18.3 (CH3) (found MH+ 151.0753.
C9H11NO2 requires 151.0759); m/z 151 (30%, MH) and
105 (100, MꢀCH2O2).
9. For related examples see: (a) Xiang, L.; Wu, H.; Hruby, V. J.
Tetrahedron: Asymmetry 1995, 6, 83–86; (b) Haigh, D.;
Birrell, H. C.; Cantello, B. C. C.; Hindley, R. M.; Ramasw-
amy, A.; Rami, H. K.; Stevens, N. C. Tetrahedron: Asymme-
try 1999, 10, 1335–1351; (c) Koll, P.; Lutzen, A. Tetrahedron:
Asymmetry 1995, 6, 43–46.
10. For a comprehensive account see Ref. 13.
11. Fukuzawa, S.-I.; Chion, Y.; Yokoyama, T. Tetrahedron:
Asymmetry 2002, 13, 1645–1649.
Acknowledgements
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We are grateful to the EPSRC for studentships (to S.G.
and Y.Y.), Onyx Scientific Limited for a CASE AWARD
(to M.D.), The Royal Society (to J.E.), The University of
London Central Research Fund (to J.E.) and Queen Mary,
University of London for their financial support (to S.C.
and M.D.), and the EPSRC National Mass Spectrometry
Service (Swansea) for accurate mass determinations.
15. Thom, C.; Kocienski, P. Synthesis 1992, 582–586.

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20. The enantiomeric purity (>98% ee) was determined by
the formation of its corresponding pentafluorophenyl
ester and subsequent chemical derivatization with oxazo-
lidinone (R)-17. For a representative reaction see Ref.
17b.
21. Interesting, by the addition of a sodiated oxazolidinone
(derived from the deprotonation of rac-4 with NaHMDS) to
rac-anti-5 (de = 99%) at ꢀ78 ꢁC for 2 h lowered the diaste-
reoisomeric excess to 84% de [rac-anti-5:syn-5 = 92:8]. By
comparison, the addition of the same sodiated oxazolidinone
to rac-syn-5 (de >99%) under identical conditions gave no
measurable change in diastereoisomeric excess. A related
stereochemical change has previously been reported; see:
Evans, D. A.; Faul, M. M.; Colombo, L.; Bisaha, J.;
Clardy, J.; Cherry, D. J. Am. Chem. Soc. 1992, 114, 5977–
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