Parallel kinetic resolution of active esters using a quasi-enantiomeric combination of (R)-4-phenyl-oxazolidin-2-one and (S)-4,5,5-triphenyl-oxazolidin-2-one

Article abstract of DOI:10.1016/j.tetasy.2008.09.012

The parallel kinetic resolution of a series of racemic pentafluorophenyl 2-(4-aryl/phenyl)-propionates and -butanoates using a quasi-enantiomeric combination of (R)-4-phenyl-oxazolidin-2-one and (S)-4,5,5-triphenyl-oxazolidin-2-one is discussed. The levels of diastereoselectivity were excellent (86-98% de) leading to separable quasi-enantiomeric oxazolidin-2-one adducts in good yield. This methodology was used to resolve 2-phenyl propionic acid.

Full text of DOI:10.1016/j.tetasy.2008.09.012

Tetrahedron: Asymmetry 19 (2008) 2223–2233
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Parallel kinetic resolution of active esters using a quasi-enantiomeric
combination of (R)-4-phenyl-oxazolidin-2-one and
(S)-4,5,5-triphenyl-oxazolidin-2-one
*
Elliot Coulbeck, Jason Eames
Department of Chemistry, University of Hull, Cottingham Road, Kingston Upon Hull HU6 7RX, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The parallel kinetic resolution of a series of racemic pentafluorophenyl 2-(4-aryl/phenyl)-propionates
and -butanoates using a quasi-enantiomeric combination of (R)-4-phenyl-oxazolidin-2-one and (S)-
4,5,5-triphenyl-oxazolidin-2-one is discussed. The levels of diastereoselectivity were excellent (86–98%
de) leading to separable quasi-enantiomeric oxazolidin-2-one adducts in good yield. This methodology
was used to resolve 2-phenyl propionic acid.
Received 12 June 2008
Accepted 17 September 2008
Available online 17 October 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Within this area, we have recently reported the parallel kinetic res-
olution of an active ester, pentafluorophenyl 2-phenylpropionate
The continuing development of novel synthetic methods for the
efficient separation of enantiomers is paramount.1 One particular
strategy that has recently attracted some attention has been the
parallel kinetic separation of enantiomers using a combination of
quasi-enantiomeric2 auxiliary components.3,4 We have been inter-
ested in the philosophy of this approach5 through the use of quasi-
enantiomeric combinations of Evans’ oxazolidin-2-ones, such as
(R)-1 and (S)-2, as mutual resolving components (Scheme 1).6
rac-3, using a combination of (lithiated) Evans’ oxazolidin-2-ones
(R)-1 and (S)-2 to give the oxazolidin-2-one adducts (S,R)-syn-4
(in 60% yield) and (R,S)-syn-5 (in 60% yield) with 90% and 76% dia-
stereoisomeric excesses, respectively (Scheme 1).6
2. Results and discussion
From this study, it was evident that the levels of stereocontrol
and mutual recognition were higher for the phenyl-glycine derived
oxazolidin-2-one (R)-1 than for its quasi-enantiomeric partner, the
valine-derived oxazolidin-2-one (S)-2 (90% de vs 76% de) (Scheme
1). In order to facilitate higher enantiomeric recognition, a better
surrogate than oxazolidin-2-one (S)-2 for the (S)-enantiomer of
4-phenyl-oxazolidin-2-one 1 was sought (Scheme 1).6
In an attempt to address this issue of complementarity, we
chose to focus our attention on the use of a Davies7/Seebach8 in-
spired designer 4,5,5-triphenyl-oxazolidin-2-one (S)-6 due to its
structural similarity to the original Evans 4-phenyl-oxazolidin-2-
one 19 (Scheme 2). We herein report our study on the use of
4,5,5-triphenyl-oxazolidin-2-one (S)-610 as a surrogate for the
O
O
1. n-BuLi,
º
THF, -78 C
HN
Ph
O
HN
O
2.
Ph
CO2C6F5
Me
rac-3
i-Pr
H
(R)-1
(S)-2
O
O
O
O
Ph
Ph
Me
N
O
N
O
H
Me
H
O
O
Ph
i-Pr
(R,S)-syn-5: (S,S)-anti-5
(S,R)-syn-4: (R,R)-anti-4
HN
Ph
O
HN
Ph
O
88:12; 60%
95:5; 60%
Ph
Scheme 1. Parallel kinetic resolution of active ester rac-3 using quasi-enantiomeric
oxazolidin-2-ones (R)-1 and (S)-2.
Ph
(R)-1
(S)-6
* Corresponding author. Tel.: +44 1482 466401; fax: +44 1482 466410.
E-mail address: j.eames@hull.ac.uk (J. Eames).
Scheme 2. Quasi-enantiomeric oxazolidin-2-ones (R)-1 and (S)-6.
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.09.012

2224
E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
O
O
O
O
O
1. n-BuLi,
THF, -78 C
Ar
Ar
º
HN
Ph
O
N
O
N
O
2.
Ar
CO2C6F5
H
R
R
H
Ph
Ph
Ph
Ph
(SR,RS)-rac-syn-
Ph
(RS,RS)-rac-anti-
H
R
Ph
Ph
Ph
rac-6
rac-
Ar
R
Oxazolidinone adducts
Yield
Active ester
D.e.
78%
Entry
rac-syn-7: rac-anti-7
rac-3
53%
83%
Ph
Me
1
2
89:11
rac-8
rac-10
rac-12
rac-syn-9: rac-anti-9
Ph
Ph
Et
94%
56%
86%
97:3
rac-syn-11: rac-anti-11
3
4
i-Pr
Me
18%
60%
78:22
4-MeC6H4-
4-ClC6H4-
rac-syn-13: rac-anti-13
93:7
5
6
rac-14
rac-16
rac-syn-15: rac-anti-15
Me
Me
84%
90%
58%
77%
92:8
rac-syn-17: rac-anti-17
4-i-BuC6H4-
95:5
Scheme 3. Mutual kinetic resolution of active esters rac-3, 8, 10, 12, 14 and 16 using oxazolidin-2-one rac-6.
(S)-enantiomer of 4-phenyl-oxazolidin-2-one 1 for the efficient
parallel kinetic resolution of a series of structurally related active
esters (Scheme 2).
With this information at hand, we next attempted the parallel
kinetic resolution of pentafluorophenyl 2-phenylpropionate rac-3
using an equimolar combination of quasi-enantiomeric oxazo-
lidin-2-ones (R)-1 and (S)-6 (Scheme 4). Treatment of an equimolar
amount of oxazolidin-2-ones (R)-1 and (S)-6 with n-BuLi in THF at
ꢀ78 °C, followed by the addition of pentafluorophenyl phenylpro-
pionate rac-3, gave after 2 h at ꢀ78 °C the corresponding syn-oxaz-
olidin-2-one adducts (S,R)-syn-4 and (R,S)-syn-7 in 58% and 60%
yields with 94% and 96% diastereoisomeric excesses, respectively
(Scheme 4: entry 1).14 The levels of enantiomer selection between
(R)-1 and (S)-3 [to give (S,R)-4], and (S)-6 and (R)-3 [to give (R,S)-7]
were excellent. For 4-phenyl-oxazolidin-2-one (R)-1, the levels of
molecular recognition were comparable for both its parallel and
mutual kinetic resolutions. In comparison, 4,5,5-triphenyl-oxazo-
lidin-2-one (S)-6 gave significantly higher levels of diastereocon-
trol for its parallel kinetic resolution (of rac-3) than its mutual
kinetic resolution (PKR: 96% de vs MKR: 78% de) (Scheme 3: entry
1 vs Scheme 4: entry 1). The levels of diastereoselection for oxazol-
din-2-one (S)-6 were also found to be dependent on the amount of
the complementary oxazolidin-2-one (R)-1 used. For example,
using non-equimolar amounts of oxazolidin-2-ones (R)-1 and (S)-
6 (in a relative ratio of 1:3 and 3:1) gave the corresponding oxaz-
olidin-2-one adducts rac-syn-4 and rac-syn-7 in 53% yield with
>96% de and 45% yield with 86% de [for (R)-1:(S)-6—ratio 1:3],
respectively, and in 65% yield with 52% de and 74% yield with
>96% de [for (R)-1:(S)-6—ratio 3:1], respectively. Interestingly, in
both cases for oxazolidin-2-one (S)-6, the levels of enantiomeric
recognition were greater than its original mutual recognition pro-
cess. Whereas, using a supra- and sub-stoichiometric amount of
oxazolidin-2-one (R)-1 gave lower and higher levels of diastereo-
control, respectively.
With this oxazolidin-2-one rac-6 in hand, we first investigated
its mutual kinetic resolution with pentafluorophenyl 2-phenylpro-
pionate rac-3 in order to determine its relative stereoselection
(Scheme 3). Deprotonation of oxazolidin-2-one rac-6 in THF at
ꢀ78 °C using n-BuLi, followed by the addition of pentafluorophenyl
2-phenylpropionate rac-3, gave after 2 h at ꢀ78 °C an inseparable
diastereoisomeric mixture of oxazolidin-2-ones (SR,RS)-syn- and
(RS,RS)-anti-7 (ratio 89:11)10,11 in a combined 53% yield (Scheme
3). Interestingly, the levels of mutual recognition between the
4,5,5-triphenyl-oxazolidin-2-one (R)-6 and the corresponding (S)-
enantiomer of active ester 3 (and its mirror image combination)
were noticeably lower than that of its parent (mutual kinetic)
resolution involving 4-phenyl-oxazolidin-2-one 1 (78% de for rac-
6 vs 94% de for rac-1).6,12
We next focused our attention on the mutual kinetic resolution
of a series of structurally related active esters rac-8, rac-10, rac-12,
rac-14 and rac-16 (derived from the DCC coupling of pentafluoro-
phenol with the corresponding carboxylic acids)12 using 4,5,5-tri-
phenyl-oxazolidin-2-one rac-6 as our mutual resolving
component under standard conditions (Scheme 3: entries 2–6).
Deprotonation of 4,5,5-triphenyl-oxazolidin-2-one rac-6 using n-
BuLi in THF at ꢀ78 °C, followed by the addition of active esters
rac-8, rac-10, rac-12, rac-14 and rac-16 in THF, gave after 2 h the
corresponding oxazolidin-2-one adducts rac-syn- and rac-anti-9,
11, 13, 15 and 17 in 18–83% yields with 56–94% diastereoisomeric
excesses (Scheme 3: entries 2–6). The levels of diastereocontrol
were found to be excellent (ranging from 56% to 94% diastereoiso-
meric excess) favouring the formation of the corresponding syn-
diastereoisomeric oxazolidin-2-one. The sterically demanding ac-
tive ester rac-8 was found to give the highest level of diastereose-
lectivity (94% de) (Scheme 3: entry 2). However, there appears to
be a sterically demanding threshold as the more sterically encum-
bered active ester rac-10 gave lower levels of stereocontrol. The
levels of diastereocontrol were found to be high for a series of ac-
tive esters rac-12, 14 and 16 derived from a variety of structurally
related 2-arylpropionic acids (Scheme 3: entry 1 vs entries 4–6).13
We next turned our attention to the parallel kinetic resolution
of a series of structurally related active esters rac-8, rac-10, rac-
12, rac-14 and rac-16 using a quasi-enantiomeric combination of
oxazolidin-2-ones (R)-1 and (S)-6 (Scheme 4: entries 2–6). Depro-
tonation of an equimolar combination of oxazolidin-2-ones (R)-1
and (S)-6 with n-BuLi in THF at ꢀ78 °C, followed by the addition
of active esters rac-8, rac-10, rac-12, rac-14 and rac-16, gave after
2 h at ꢀ78 °C the corresponding oxazolidin-2-one adducts (S,R)-

E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
2225
O
O
O
O
O
O
1. n-BuLi,
THF, -78 C
Ar
Ar
º
HN
Ph
O
N
O
N
O
HN
Ph
O
2.
H
R
R
H
Ar
CO2C6F5
Ph
Ph
Ph
(S,R)-syn-
Ph
Ph
Ph
H
rac-
R
(R)-1
(R,S)-syn-
(S)-6
Oxazolidinone adducts
Oxazolidinone adducts
Entry
Ratio
Active ester
Ar
R
D.e.
94%
Yield
58%
D.e.
96%
94%
Yield
60%
59%
derived from (R)-1
derived from (S)-6
rac-3
(S,R)-syn-4: (R,R)-anti-4
(R,S)-syn-7: (S,S)-anti-7
1
2
Ph
Ph
4: 7
52:48
Me
Et
97:3
98:2
rac-8
(S,R)-syn-18: (R,R)-anti-18
(R,S)-syn-9: (S,S)-anti-9
18: 9
50:50
98%
54%
63%
79%
99:1
97:3
rac-10
(S,R)-syn-19: (R,R)-anti-19
(R,S)-syn-11: (S,S)-anti-11
3
Ph
i-Pr
Me
Me
Me
43%
51%
60%
55%
19: 11
69:31
76%
96%
92%
88:12
77:23
4-MeC6H4-
4-ClC6H4-
rac-12
rac-14
(S,R)-syn-20: (R,R)-anti-20
98%
86%
94%
(R,S)-syn-13: (S,S)-anti-13
20: 13
50:50
4
5
45%
71%
99:1
98:2
(R,S)-syn-15: (S,S)-anti-15
(S,R)-syn-21: (R,R)-anti-21
21: 15
52:48
96:4
93:7
rac-16
4-i-BuC6H4-
(S,R)-syn-22: (R,R)-anti-22
(R,S)-syn-17: (S,S)-anti-17
6
60%
96%
22: 17
56:44
97:3
98:2
Scheme 4. Parallel kinetic resolution of active esters rac-3, 8, 10, 12, 14 and 16 using a combination of quasi-enantiomeric oxazolidin-2-ones (R)-1 and (S)-6.
syn-18 and (R,S)-syn-9 (in 63% and 59% yields for rac-8), (S,R)-syn-
19 and (R,S)-syn-11 (in 79% and 43% yields for rac-10), (S,R)-syn-20
and (R,S)-syn-13 (in 45% and 51% yields for rac-12), (S,R)-syn-21
and (R,S)-syn-15 (in 71% and 60% yields for rac-14) and (S,R)-syn-
22 and (R,S)-syn-17 (in 60% and 55% yields for rac-16) with excel-
lent diastereoselectivities (54–98% de) (Scheme 4: entries 2–6).
Interestingly, in agreement with the previous study, the levels of
diastereoselection were found to be higher for the 4,5,5-tri-
phenyl-oxazolidin-2-one (S)-1 [in the presence of oxazolidin-2-
one (R)-1] than their corresponding mutual kinetic resolutions
(Scheme 3 vs Scheme 4).
These reactions proceeded efficiently to give access to easily
separable syn-oxazolidin-2-one adducts, such as (S,R)-syn-18 and
(R,S)-syn-9 [derived from Evans’ and Seebach’s oxazolidin-2-ones
(R)-1 and (S)-6, respectively, and the corresponding active ester
rac-8];
DRf [light petroleum ether (bp 40–60 °C)/diethyl ether
(1:1)] = 0.30.
We next focussed our attention on the complementary parallel
kinetic resolution of 4,5,5-triphenyl-oxazolidin-2-one rac-6 using a
quasi-enantiomeric combination of separable active esters15 (S)-23
and (R)-8 (Scheme 5). Treatment of 4,5,5-triphenyl-oxazolidin-2-
one rac-6 with n-BuLi in THF at ꢀ78 °C, followed by the addition
O
1. n-BuLi,
THF, -78ºC
HN
Ph
O
2.
MeO
Ph
Ph
CO2C6F5
rac-6
H
Me
(S)-23
Ph CO2C6F5
Et
H
(R)-8
MeO
O
O
O
O
Ph
Et
N
O
N
O
H
Me
H
Ph
Ph
Ph
Ph
Ph
Ph
(S,R)-syn-24
syn-:anti-: 96:4; 92% d.e.; 43%
43:57
(R,S)-syn-9
syn-:anti-: 96:4; 92% d.e.; 57%
Scheme 5. Parallel kinetic resolution of oxazolidin-2-one rac-6 using active esters (S)-23 and (R)-8.

2226
E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
O
O
1. n-BuLi,
º
THF, -78 C
HN
Ph
O
HN
Ph
O
2.
MeO
Ph
CO2C6F5
Me
(S)-23
Ph
H
(R)-1
(S)-6
Ph CO2C6F5
Et
H
(R)-8
MeO
O
O
O
O
Ph
N
O
N
O
H
Me
Et
H
Ph
Ph
Ph
Ph
(S,R)-syn-25
(S,R)-syn-25: (R,R)-anti-18
syn-:anti-: >95: 5;48%
(R,S)-syn-9
(R,S)-syn-9: (S,S)-anti-24
35:65
syn-:anti-: >95:5; 67%
Scheme 6. Mutual kinetic separation of oxazolidin-2-ones (R)-1 and (S)-6 using active esters (S)-23 and (R)-8.
of an equimolar amount of active esters (S)-23 and (R)-8 in THF,
gave after 2 h at ꢀ78 °C the corresponding oxazolidin-2-one ad-
ducts (S,R)-syn-24 and (R,S)-syn-9 in 43% and 57% yields, respec-
tively, with an equal 92% diastereoisomeric excess (Scheme 5).
These adducts were efficiently separated/isolated by column chro-
(Scheme 7). Deprotonation of an equimolar amount of oxazo-
lidin-2-ones 26 and rac-6 with n-BuLi (2.2 equiv) at ꢀ78 °C in
THF, followed by the addition of active ester rac-3, gave a separable
mixture of the oxazolidin-2-ones 27 (in 63% yield) and rac-syn-7
(in 37% yield with 90% de) (Scheme 7). Interestingly, the mutual
kinetic resolution of oxazolidin-2-one rac-6 with active ester rac-
3 appeared to mimic the outcome derived from its traditional
kinetic resolution, whereas using the achiral oxazolidin-2-one 26
(as a complementary surrogate) allowed the reaction to proceed
matography due to their difference in polarity {DRf [light petro-
leum ether (bp 40–60 °C)/diethyl ether (1:1)] = 0.14}. The levels
of molecular recognition were also found to be similar to those
of their parent mutual kinetic resolutions (as shown in Scheme 3).
With this information at hand, we next investigated the config-
urational stability of these active esters by probing their mutual ki-
netic separation. Treatment of a pair of quasi-enantiomeric active
esters (S)-23 and (R)-8 with a quasi-enantiomeric combination of
lithiated oxazolidin-2-ones [formed by n-BuLi deprotonation of
(R)-1 and (S)-6], gave the corresponding oxazolidin-2-one adducts
(S,R)-syn-25 and (R,S)-syn-9 in 48% and 67% yields, respectively,
with high levels of enantiomeric (and substrate) recognition
(Scheme 6). From this study, it appears that these active esters
(S)-23 and (R)-8 were configurationally stable under these reaction
conditions as the corresponding diastereoisomeric adducts (R,R)-
anti-25 and (S,S)-anti-9 were absent (as determined by 400 MHz
1H NMR spectroscopy) (Scheme 6). The levels of enantiomer selec-
tion between (R)-1 and (S)-23 [to give (S,R)-syn-25], and (S)-6 and
(R)-8 [to give (R,S)-syn-9] were excellent. Interestingly, these levels
of enantiomeric recognition were noticeably higher than those that
were suggested from the parent mutual kinetic resolution of See-
bach’s oxazolidin-2-one rac-6 with the active ester rac-3 [to give
the oxazolidin-2-one adduct rac-syn-7 in 53% with 78% de (Scheme
3: entry 1)].
In an attempt to probe this apparent anomaly, we next investi-
gated the kinetic resolution of active ester rac-3 (2 equiv) using
Seebach’s oxazolidin-2-one (S)-6 (1 equiv) (Scheme 7). Treatment
of oxazolidin-2-one (S)-6 with n-BuLi in THF at ꢀ78 °C, followed
by the addition of active ester rac-3 (2 equiv), gave an inseparable
diastereoisomeric mixture of oxazolidin-2-one adducts (R,S)-syn-
and (S,R)-anti-7 in 75% yield (ratio 85:15) (Scheme 7).16 The levels
of diastereoisomeric control were found to be surprisingly similar
for both the kinetic (70% de) and mutual resolutions (78% de) of the
same racemic active ester 3 (Schemes 3 and 7). However, these
levels of diastereocontrol could be improved to >90% de by the
addition of the simplest achiral oxazolidin-2-one surrogate 26
O
O
O
1. n-BuLi,
THF, -78 C
Ph
Me
º
HN
Ph
O
N
O
2.
H
Ph
CO2C6F5
(2 equiv.)
Ph
Ph
Ph
Ph
Ph
H
rac-3
Me
(1 equiv.)
(S)-6
(R,S)-syn-7: (S,S)-anti-7
85:15; 70% d.e.; 75%
O
O
1. n-BuLi,
º
THF, -78 C
HN
Ph
O
HN
O
O
2.
Ph
CO2C6F5
Me
Ph
Ph
H
26
rac-6
rac-3
O
O
O
Ph
Ph
N
O
N
O
H
Me
Me
H
Ph
Ph
Ph
rac-syn-7: rac-anti-7
95:5; 90% d.e.; 37%
rac-27; 63%
63:37
Scheme 7. Kinetic and mutual resolutions of oxazolidin-2-ones (S)- and rac-6 using
active ester rac-3.

E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
2227
O
O
O
Ph
CO2H
Me
Ph
LiOH, H2O2
THF, H2O
N
O
HN
Ph
O
H
H
Me
Ph
(S,R)-syn-4; 96% d.e.
(S)-28; 91%; 96% e.e.
(R)-1; 95%
O
O
O
Ph
Me
CO2H
Ph
Me
LiOH, H2O2
THF, H2O
N
O
HN
Ph
O
H
H
Ph
Ph
Ph
Ph
Ph
(R)-28; 58%; 96% e.e.
(R,S)-syn-7; 96% d.e.
(S)-6; 95%
Scheme 8. Hydrolysis of oxazolidin-2-one adducts (S,R)-syn-4 and (R,S)-syn-7.
via a more diastereoselective mutual kinetic resolution pathway.
From this study, it appears that hetero-aggregation between the
lithiated oxazolidin-2-ones (derived from rac-6 and 26) is in-part
responsible for this increase in diastereoselection.
Access to both enantiomers of 2-phenylpropionic acid (S)- and
(R)-28 was achieved through hydrolysis [LiOH monohydrate/
hydrogen peroxide in THF/H2O (3:1)] of a pair of quasi-enantio-
meric adducts [e.g., (S,R)-syn-4 and (R,S)-syn-7] in 91% and 58%
yields, respectively (Scheme 8).17
4.2. Synthesis of pentafluorophenyl 2-phenyl-3-methyl-
butanoate rac-10
Pentafluorophenol (0.5 g, 2.72 mmol) in dichloromethane
(5 mL) was added to N,N0-dicyclohexylcarbodiimide (0.62 g,
3.00 mmol) in dichloromethane (5 mL), and the resulting solution
was stirred for 5 min. A solution of racemic 2-phenyl-3-methyl
butanoic acid (0.48 g, 2.72 mmol) in dichloromethane (20 mL)
was added in four equal portions over 1 h. The solution was stirred
for 12 h and the resulting precipitate (N,N0-dicyclohexylurea) was
filtered off (using suction filtration). Brine (30 mL) was added
and the solution was extracted into dichloromethane
(3 ꢁ 50 mL). The combined organic layers were dried over MgSO4
and evaporated under reduced pressure. The crude residue was
purified by flash column chromatography on silica gel eluting with
light petroleum ether (bp 40–60 °C)/diethyl ether (9:1) to give
pentafluorophenyl 2-phenyl-3-methyl butanoate rac-10 (0.69 g,
74%) as a white crystalline solid; Rf [light petroleum ether (bp
3. Conclusion
In conclusion, we have reported the efficient parallel kinetic
resolution of a series of active esters (e.g., rac-3) using an equimo-
lar quasi-enantiomer combination of 4-phenyl-oxazolidin-2-one
(R)-1 and 4,5,5-triphenyl-oxazolidin-2-one (S)-6. The levels of dia-
stereocontrol were found to be excellent, favouring the formation
of the corresponding syn-oxazolidin-2-one adducts (S,R)-syn-4
and (R,S)-syn-7 in good yields with excellent levels of diastereo-
selectivity. This combination of oxazolidin-2-ones was shown to
be efficient quasi-enantiomers for the parallel kinetic resolution
and separation of a variety of structurally related 2-aryl propionic
and butanoic acids.
40–60 °C)/diethyl ether (9:1)] 0.77; mp 40–42 °C; m
max (film) cmꢀ1
1776 (C@O); dH (400 MHz; CDCl3) 7.39–7.31 (5H, m, 5 ꢁ CH; Ph),
3.51 (1H, d, J 10.3, PhCHi-Pr), 2.51–2.40 (1H, m, CH(CH3)2), 1.15
(3H, d, J 6.6, CHACHCHB) and 0.79 (3H, d, J 6.6, CHACHCHB); dC
3
3
3
3
(100 MHz; CDCl3) 169.9 (C@O), 141.1 (142.37 and 139.88, 2 C,
1
2
3
ddt, JC,F = 251.4 Hz, JC,F = 12.3 Hz and JC,F = 3.8 Hz, C(2)–F),
1
2
139.4 (140.65 and 138.14, 1C, dtt, JC,F = 252.9 Hz, JC,F = 13.8 Hz
4. Experimental
4.1. General
3
and JC,F = 4.6 Hz, C(4)–F), 137.8 (139.05 and 136.58, 2C, dtdd,
1JC,F = 249.1 Hz, JC,F = 13.1 Hz, JC,F = 5.4 Hz and JC,F = 3.1 Hz,
2
3
4
C(3)–F), 136.4 (i-C; Ph), 128.82, 128.52 and 127.91 (5 ꢁ CH; Ph),
2
4
3
125.1 (1 C, tdt, JC,F = 14.6 Hz, JC,F = 4.6 Hz and JC,F = 2.3 Hz, i-CO;
OC6F5), 59.2 (PhCHi-Pr), 31.8 (CH(CH3)2), 21.2 (CHACHCHB) and
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 chromatography (TLC) was carried out on
commercially available pre-coated plates (Merck Kieselgel 60F254
silica). Proton and carbon NMR spectra were recorded on a Bruker
400 MHz Fourier transform spectrometer using an internal
deuterium lock. Chemical shifts are quoted in parts per million
downfield from tetramethylsilane. Carbon NMR spectra were
recorded with broad proton decoupling. Infrared spectra were
recorded on a Shimadzu 8300 FTIR spectrometer. Optical rotations
were measured using an automatic AA-10 Optical Activity Ltd
polarimeter. The active esters, pentafluorophenyl 2-phenyl-
propionate rac-3, pentafluorophenyl 2-phenylbutanoate rac-8,
pentafluorophenyl 2-(4-methylphenyl)propionate rac-12 and
pentafluorophenyl 2-(4-isobutylphenyl)propionate rac-16, have
been reported elsewhere.12
3
3
20.0 (CHACHCHB); dF (378 MHz; CDCl3) ꢀ152.3 (2 F, dt, 3JF,F 17.3
3
3
4
3
and JF,F 4.8, Fortho), ꢀ158.0 (1F, t, JF,F 21.9, Fpara) and ꢀ162.4 (2F,
3
4
+
td, JF,F 21.9 and JF,F 4.8 Fmeta) (Found M+ 344.0829; C17H13F5O2
requires M+ 344.0830); m/z 344 (10%, M+), 133 [65, (PhCHC3H7)+]
and 91 [100, (PhCH2)+].
4.3. Synthesis of pentafluorophenyl 2-(4-chlorophenyl)-
propionate rac-12
In the same way as the active ester rac-10, 4-chlorophenylprop-
ionic acid (1.49 g, 8.11 mmol), N,N0-dicyclohexylcarbodiimide
(1.84 g, 8.92 mmol) and pentafluorophenol (1.49 g, 8.11 mmol)
gave the pentafluorophenyl 2-(4-chlorophenyl)propionate rac-12
(2.61 g, 92%) as a white solid; Rf [light petroleum ether (bp 40–
60 °C)/diethyl ether (1:1)] 0.82; mp 37–40 °C; mmax (film) cmꢀ1

2228
E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
1782 (C@O); dH (400 MHz; CDCl3) 7.35 (2H, dt, J 8.6 and 2.2,
2 ꢁ CH; Ar), 7.29 (2H, dt, J 8.6 and 2.2, 2 ꢁ CH; Ar), 4.04 (1H, q, J
7.1, ArCHCH3) and 1.63 (3H, d, J 7.1, ArCHCH3); dC (100 MHz;
CDCl3) 170.2 (C@O), 141.1 (142.29 and 139.78, 2C, ddt,
br d, J 7.5, Ph), 6.20 (1H, s, CHN), 4.72 (1H, t, J 7.3, ArCHEt), 1.97–
1.85 (1H, m, CHAHBCH3), 1.69–1.57 (1H, m, CHAHBCH3) and 0.70
(3H, t, J 7.3, CH3CHAHB); dC (100 MHz; CDCl3) 172.8 (NC@O),
152.1 (OC@O), 141.7, 138.0 and 135.0 (3 ꢁ i-C; 3 ꢁ Ph), 137.7
(i-C; PhCHEt), 128.93, 128.82, 128.32, 127.92, 127.81, 127.52,
127.41, 127.32, 127.11, 126.32 and 126.22 (20 ꢁ CH; 4 ꢁ Ph), 88.6
(CPh2O), 65.9 (CHN), 51.1 (ArCHEt), 26.7 (CH2CH3) and 11.8
(CH2CH3) (Found MH+, 462.2067; C31H28NO3 requires MH+,
462.2064).
2
3
1JC,F = 250.6 Hz, JC,F = 12.2 Hz and JC,F = 3.8 Hz, C(2)–F), 139.5
1
2
(140.73 and 138.21, 1C, dtt, JC,F = 252.1 Hz, JC,F = 13.7 Hz and
3JC,F = 3.8 Hz, C(4)–F), 137.8 (139.05 and 136.54, 2C, dtdd,
1JC,F = 250.9 Hz, JC,F = 14.5 Hz, JC,F = 5.3 Hz and JC,F = 3.1 Hz,
C(3)–F), 137.1 (i-CCl; Ar), 133.7 (i-C; Ar), 129.12 and 128.82
(4 ꢁ CH; Ar), 125.0 (1 C, tdt, 2JC,F = 14.5 Hz, 4JC,F = 5.3 Hz
2
3
4
3
and JC,F = 3.0 Hz, i-CO; OC6F5), 44.4 (ArCH) and 18.5 (CH3CH);
4.6. Mutual kinetic resolution of pentafluorophenyl 2-phenyl-
3-methylbutanoate rac-10 using 4,5,5-triphenyl oxazolidin-2-
one rac-6
(Found M(35Cl)+, 350.0124; C15H8ClF5O2 requires M(35Cl)+,
350.0127).
4.4. Mutual kinetic resolution of pentafluorophenyl 2-
phenylpropionate rac-3 using 4,5,5-triphenyl oxazolidin-
2-one rac-6
In the same way as oxazolidin-2-one 7, n-butyl lithium
(0.14 mL, 2.5 M in hexane, 0.35 mmol), 4,5,5-triphenyl-oxazo-
lidin-2-one rac-6 (0.10 g, 0.32 mmol) and pentafluorophenyl
2-phenyl-3-methylbutanoate rac-10 (0.11 g, 0.32 mmol) gave a
diastereoisomeric mixture of oxazolidin-2-ones rac-syn- and rac-
anti-11 (ratio 78:22: syn-:anti-). The crude residue was purified
by flash chromatography on silica gel eluting with light petroleum
ether (bp 40–60 °C)/diethyl ether (7:3) to give an inseparable mix-
ture of (2RS,4SR)-3-(2-phenyl-3-methylbutanoyl)-4,5,5-triphenyl-
oxazolidin-2-one rac-syn-11 and (2RS,4RS)-3-(2-phenyl-3-meth-
ylbutanoyl)-4,5,5-triphenyl-oxazolidin-2-one rac-anti-11 (27 mg,
18%, ratio 78:22, 56% de in favour of syn-) as a white solid; Rf [light
petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.71; mp 166–
172 °C; mmax (CHCl3) cmꢀ1 1780 (OC@O) and 1702 (NC@O); dH
(400 MHz; CDCl3) 7.57 (2H, br d, J 7.7, 2 ꢁ CH; Ph)2s, 7.40–7.30
(8H, m, 4 ꢁ CH; Ph)3s+5a, 7.19–7.00 (10H, m, 10 ꢁ CH; Ph),5s+5a
6.95–6.70 (18H, m, 16 ꢁ CH; Ph),8s+10a 6.53 (2H, br d, J 7.7,
2 ꢁ CH; Ph),2s 6.19 (1H, s, PhCHN),s 5.98 (1H, s, PhCHN),a 4.70
(1H, d, J 10.3, PhCHi-Pr),a 4.55 (1H, br d, J 10.1, PhCHi-Pr),s 2.35–
n-BuLi (0.28 mL, 2.5 M in hexane, 0.70 mmol) was added to a
stirred solution of 4,5,5-triphenyl-oxazolidin-2-one rac-6 (0.20 g,
0.63 mmol) in THF at ꢀ78 °C. After stirring for 1 h, a solution of
pentafluorophenyl 2-phenylpropionate rac-3 (0.20 g, 0.63 mmol)
in THF (1 mL) was added. The resulting mixture was stirred for
2 h at ꢀ78 °C. The reaction mixture was quenched with water
(10 mL). The organic layer was extracted with dichloromethane
(3 ꢁ 10 mL), dried over MgSO4 and evaporated under reduced
pressure to give a mixture of diastereoisomeric oxazolidin-2-ones
7 [ratio 89:11: syn-:anti-]. The crude residue was purified by flash
chromatography on silica gel eluting with light petroleum ether
(bp 40–60 °C)/diethyl ether (7:3) to give the (2RS,4SR)-3-(2-phen-
ylpropionyl)-4,5,5-triphenyl-oxazolidin-2-one rac-syn-7 (0.15 g,
53%, 78% de) as a white powder; Rf [light petroleum ether (bp
40–60 °C)/diethyl ether (1:1)] 0.58; mp 160–165 °C; mmax
(CHCl3) cmꢀ1 1780 (OC@O) and 1704 (NC@O); dH (400 MHz;
CDCl3) 7.63 (2H, br d, J 7.7, 2 ꢁ CH; Ph), 7.46–7.36 (4H, m,
4 ꢁ CH; Ph), 7.19 (2H, dd, J 5.0, and 2.0, 2 ꢁ CH; Ph), 7.11–7.07
(2H, m, 2 ꢁ CH; Ph), 7.01–6.86 (8H, m, 8 ꢁ CH; Ph), 6.65 (2H, br
d, J 7.7, 2 ꢁ CH; Ph), 6.25 (1H, s, CHN), 4.98 (1H, q, J 7.0, PhCHCH3)
and 1.35 (3H, d, J 7.0, PhCHCH3); dC (100 MHz; CDCl3) 173.2
(NC@O), 152.0 (OC@O), 141.8, 138.0 and 135.0 (3 ꢁ i-C; 3 ꢁ Ph–
oxazolidin-2-one), 139.5 (i-C; Ph), 128.92, 128.81, 128.42, 128.32,
127.93, 127.62, 127.51, 127.42, 127.01, 126.22 and 126.12
(20 ꢁ CH; 4 ꢁ Ph), 88.5 (CPh2O), 66.0 (CHN), 44.0 (PhCHCH3) and
19.0 (PhCHCH3) (Found M+, 447.1835; C30H25NO3 requires M+,
447.1829); m/z 447 (10%, M+), 315 (5, Mꢀ Ph(CH3)C@C@O+), 256
(15, PhCHCPh2þ), 183 (20, Ph2C@OH+), 105 (100, PhCH@NH+) and
77 (20, Ph+).
2.19 (2H, m, 2 ꢁ CH(CH3)2),s+a 0.77 (6H, d,
J
6.9,
2 ꢁ CHA3 CHCH3B),3s+3a 0.58 (3H, d, J 6.9, CH3ACHCH3B)3a and 0.55
(3H, d, J 6.9, CH3ACHCH3B)3s; dC (100 MHz; CDCl3) 173.7 (NC@O),a
172.8 (NC@O),s 152.6 (OC@O),a 152.3 (OC@O),s 141.6, 137.8,
136.9 and 134.9 (4 ꢁ i-C; 4 ꢁ Ph),4s 141.3, 137.6, 136.6 and 136.0
(4 ꢁ i-C; 4 ꢁ Ph),4a 129.32s
, , , , ,
128.91s 128.82s 128.22s 127.92s
127.7,1s 127.52s, 127.41s, 127.11s, 127.02s, 126.32s and 126.42s
(20 ꢁ CH; 4 ꢁ Ph),20s 129.3,2a 128.9,1a 128.62a, 128.51a, 128.32a
,
128.22a, 128.01a, 127.6,2a 127.52a, 127.1,1a 126.42a and 125.92a
(20 ꢁ CH; 4 ꢁ Ph),20a 88.7 (CPh2O),1a 88.6 (CPh2O),1s 66.6 (CHN),1a
65.8 (CHN),1s 56.7 (PhCHi-Pr),1s 56.1 (PhCHi-Pr),1a 31.6
(CH(CH3)2)1a, 31.5 (CH(CH3)2)1s, 21.43a, 21.33s, 20.03a and 20.03s
(4 ꢁ CH3)6s+6a (Found MNH4
, 493.2488; C32H33N2O3 requires
þ
MNH4þ, 493.2486).
4.5. Mutual kinetic resolution of pentafluorophenyl 2-
phenylbutanoate rac-8 using 4,5,5-triphenyl oxazolidin-
2-one rac-6
4.7. Mutual kinetic resolution of pentafluorophenyl
2-(4-methylphenyl)propionate rac-12 using 4,5,5-triphenyl
oxazolidin-2-one rac-6
In the same way as oxazolidin-2-one 7, n-butyl lithium
(0.14 mL, 2.5 M in hexane, 0.35 mmol), 4,5,5-triphenyl-oxazo-
lidin-2-one rac-6 (0.10 g, 0.32 mmol) and pentafluorophenyl
2-phenylbutanoate rac-8 (0.105 g, 0.32 mmol) gave a diastereoiso-
meric mixture of oxazolidin-2-ones rac-syn- and rac-anti-9 (ratio
97:3: syn-:anti-). The crude residue was purified by flash chroma-
tography on silica gel eluting with light petroleum ether (bp 40–
60 °C)/diethyl ether (7:3) to give the (2RS,4SR)-3-(2-phenylbuta-
noyl)-4,5,5-triphenyl-oxazolidin-2-one rac-syn-9 (0.121 g, 83%,
94% de) as a white solid; Rf [light petroleum ether (bp 40–60 °C)/
diethyl ether (1:1)] 0.61; mp 158–160 °C; mmax (CHCl3) cmꢀ1
1780 (OC@O) and 1707 (NC@O); dH (400 MHz; CDCl3) 7.57 (2H,
br d, J 7.5, 2 ꢁ CH; Ph), 7.41–7.30 (3H, m, 3 ꢁ CH; Ph), 7.16–7.05
(5H, m, 5 ꢁ CH; Ph), 6.94–6.79 (8H, m, 8 ꢁ CH; 3 ꢁ Ph), 6.57 (2H,
In the same way as oxazolidin-2-one 7, n-butyl lithium
(0.14 mL, 2.5 M in hexane, 0.35 mmol), 4,5,5-triphenyl-oxazo-
lidin-2-one rac-6 (0.10 g, 0.32 mmol) and pentafluorophenyl
2-(4-methylphenyl)propionate rac-12 (0.105 g, 0.32 mmol) gave a
diastereoisomeric mixture of oxazolidin-2-ones rac-syn- and rac-
anti-13 (ratio 93:7: syn-:anti-). The crude residue was purified by
flash chromatography on silica gel eluting with light petroleum
ether (bp 40–60 °C)/diethyl ether (7:3) to give the (2RS,4SR)-
3-[2-(4-methylphenyl)propionyl]-4,5,5-triphenyl-oxazolidin-2-one
rac-syn-13 (88 mg, 60%, 86% de) as a white solid; Rf [light petro-
leum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.57; mp 153–
158 °C; mmax (CHCl3) cmꢀ1 1780 (OC@O) and 1703 (NC@O); dH
(400 MHz; CDCl3) 7.64 (2H, br d, J 7.7, 2 ꢁ CH; Ar), 7.48–7.38
(3H, m, 3 ꢁ CH; Ph), 7.04–6.89 (12H, m, 12 ꢁ CH; Ph), 6.69 (2H,

E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
2229
br d, J 7.7, Ar), 6.26 (1H, s, CHN), 4.95 (1H, q, J 7.0, ArCHCH3), 2.32
4.10. Parallel kinetic resolution of pentafluorophenyl
2-phenylpropionate rac-3 using a quasi-enantiomeric
combination of 4-phenyloxazolidin-2-one (R)-1 and 4,5,5-
triphenyl oxazolidin-2-one (S)-6
(3H, s, CH3Ar) and 1.35 (3H, d, J 7.0, ArCHCH3); dC (100 MHz; CDCl3)
173.4 (NC@O), 152.0 (OC@O), 141.8, 138.0 and 135.1 (3 ꢁ i-C;
3 ꢁ Ph), 136.6 and 136.5 (2 ꢁ i-C; 2 ꢁ Ar), 129.12, 128.92, 128.91,
128.12, 127.93, 127.52, 127.42, 127.31, 126.32 and 126.12
(19 ꢁ CH; 3 ꢁ Ph and Ar), 88.5 (CPh2O), 66.0 (CHN), 44.6
(ArCHCH3), 21.1 (CH3Ar) and 19.1 (ArCHCH3) (Found MH+,
462.2062; C31H28NO3 requires MH+, 462.2064).
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(0.28 mL, 2.5 M in hexane, 0.70 mmol), 4-phenyl-oxazolidin-2-one
(R)-1 (50 mg, 0.32 mmol), 4,5,5-triphenyl-oxazolidin-2-one (S)-6
(0.10 g, 0.32 mmol) and pentafluorophenyl 2-phenylpropionate
rac-3 (0.20 g, 0.63 mmol) gave a mixture of two diastereoisomeric
oxazolidin-2-ones (S,R)-4 (ratio 97:3: syn-:anti-) and (R,S)-7 (ratio
98:2: syn-:anti-). The crude residue was purified by flash
chromatography on silica gel eluting with light petroleum ether
(bp 40–60 °C)/diethyl ether (7:3) to give the (2S,4R)-3-(2-phenyl-
propionyl)-4-phenyl-oxazolidin-2-one (S,R)-syn-4 (54 mg, 58%) as
a white solid; mp 140–142 °C; Rf [light petroleum ether (bp 40–
60 °C)/diethyl ether (1:1)] 0.23; mmax (CHCl3) cmꢀ1 1778 (OC@O)
4.8. Mutual kinetic resolution of pentafluorophenyl
2-(4-chlorophenyl)propionate rac-14 using 4,5,5-triphenyl
oxazolidin-2-one rac-6
In the same way as oxazolidin-2-one 7, n-butyl lithium
(0.14 mL, 2.5 M in hexane, 0.35 mmol), 4,5,5-triphenyl-oxazo-
lidin-2-one rac-6 (0.10 g, 0.32 mmol) and pentafluorophenyl
2-(4-chlorophenyl)propionate rac-14 (0.11 g, 0.32 mmol) gave a
diastereoisomeric mixture of oxazolidin-2-ones rac-syn- and
rac-anti-15 (ratio 92:8: syn-:anti-). The crude residue was purified
by flash chromatography on silica gel eluting with light petroleum
ether (bp 40–60 °C)/diethyl ether (7:3) to give the (2RS,4SR)-3-[2-
(4-chlorophenyl)propionyl]-4,5,5-triphenyl-oxazolidin-2-one rac-
syn-15 (88 mg, 58%, 84% de) as a white solid; Rf [light petroleum
ether (bp 40–60 °C)/diethyl ether (1:1)] 0.68; mp 135–138 °C; mmax
(CHCl3) cmꢀ1 1781 (OC@O) and 1708 (NC@O); dH (400 MHz;
CDCl3) 7.58 (2H, br d, J 7.7, 2 ꢁ CH; Ph), 7.40–7.30 (3H, m,
3 ꢁ CH; Ph), 7.10 (2H, dt, J 8.2 and 1.9, 2 ꢁ CH; Ar), 6.94 (2H, dt, J
8.2 and 1.9, 2 ꢁ CH; Ar), 6.99–6.82 (8H, m, 8 ꢁ CH; Ph), 6.60 (2H,
br d, J 7.2, Ph), 6.19 (1H, s, CHN), 4.90 (1H, q, J 7.0, ArCHCH3),
1.28 (3H, d, J 7.0, ArCHCH3); dC (100 MHz; CDCl3) 172.8 (NC@O),
151.9 (OC@O), 141.8, 138.0, 137.9, 134.9 and 132.8 (5 ꢁ i-C;
3 ꢁ Ph and 2 ꢁ Ar), 129.62, 128.92, 128.91, 128.52, 128.01, 127.92,
127.62, 127.41, 127.42, 126.12 and 126.02 (19 ꢁ CH; 3 ꢁ Ph and
and 1701 (NC@O);
½
a 2D0
ꢃ
¼ þ92:5 (c 4.9, CHCl3); {lit.18
½
a 2D0
ꢃ
¼ þ88:5 (c 4.0, CHCl3)}; dH (400 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, PhCHCH3), 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, PhCHCH3); dC
(100 MHz; CDCl3) 173.7 (NC@O), 153.2 (OC@O), 139.9 (i-C; PhA),
138.3 (i-C; PhB), 128.9,2 128.5,3 128.2,2 127.11 and 125.92
(10 ꢁ CH; 2 ꢁ Ph), 69.6 (CH2O), 57.9 (CHN), 43.9 (PhCHCH3) and
18.6 (PhCHCH3) (Found MH+, 296.1286; C15H18NO3 requires
þ
296.1287); and (2R,4S)-3-(2-phenylpropionyl)-4,5,5-triphenyl-
oxazolidin-2-one (R,S)-syn-7 (0.85 mg, 60%, 96% de) as a white
powder; Rf [light petroleum ether (bp 40–60 °C)/diethyl ether
(1:1)] 0.63; mp 154–156 °C; ½a D20
¼ ꢀ255:1 (c 3.4, CHCl3); mmax
ꢃ
(CHCl3) cmꢀ1 1780 (NC@O) and 1704 (OC@O); dH (400 MHz;
CDCl3) 7.63 (2H, br d, J 7.7, 2 ꢁ CH; Ph), 7.46–7.36 (4H, m,
4 ꢁ CH; Ph), 7.19 (2H, br dd, J 5.0, and 2.0, 2 ꢁ CH; Ph), 7.11–7.07
(2H, m, 2 ꢁ CH; Ph), 7.01–6.86 (8H, m, 8 ꢁ CH; Ph), 6.65 (2H, br
d, J 7.7, 2 ꢁ CH; Ph), 6.25 (1H, s, CHN), 4.98 (1H, q, J 7.0, PhCHCH3)
and 1.35 (3H, d, J 7.0, PhCHCH3); dC (100 MHz; CDCl3) 173.2
(OC@O), 152.0 (NC@O), 141.8, 138.0 and 135.0 (3 ꢁ i-C; 3 ꢁ Ph–
oxazolidin-2-one), 139.5 (i-C; Ph), 128.92, 128.81, 128.42, 128.32,
127.93, 127.62, 127.51, 127.42, 127.01, 126.22 and 126.12
(20 ꢁ CH; 4 ꢁ Ph), 88.5 (CPh2O), 66.0 (CHN), 44.0 (PhCHCH3) and
19.0 (PhCHCH3) (Found MH+, 448.1908; C30H26NO3 requires
448.1907); m/z 447 (10%, M+), 315 (5, M+ꢀPh(CH3)C@C@O), 256
(15, PhCHCPh2þ), 183 (20, Ph2C@OH+), 105 (100, PhCH@NH+) and
77 (20, Ph+).
Ar), 88.6 (CPh2O), 65.9 (CHN), 43.3 (ArCHCH3) and 18.9 (ArCHCH3)
þ
(Found
Mð35ClÞNH4
,
499.1786;
C30H28ClN2O3
requires
Mð35ClÞNH4þ, 499.1783).
4.9. Mutual kinetic resolution of pentafluorophenyl
2-(4-isobutylphenyl)propionate rac-16 using 4,5,5-triphenyl
oxazolidin-2-one rac-6
In the same way as oxazolidin-2-one 7, n-butyl lithium
(0.14 mL, 2.5 M in hexane, 0.35 mmol), 4,5,5-triphenyl-oxazo-
lidin-2-one rac-6 (0.10 g, 0.32 mmol) and pentafluorophenyl
2-(4-isobutylphenyl)propionate rac-16 (0.118 g, 0.32 mmol), gave
a diastereoisomeric mixture of oxazolidin-2-ones rac-syn- and
rac-anti-17 (ratio 95:5: syn-:anti-). The crude residue was purified
by flash chromatography on silica gel eluting with light petroleum
ether (bp 40–60 °C)/diethyl ether (7:3) to give the (2RS,4SR)-3-
[2-(4-isobutylphenyl)propionyl]-4,5,5-triphenyl-oxazolidin-2-one
rac-syn-17 (0.125 g, 77%, 90% de) as a white solid; Rf [light petro-
leum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.73; mp 158–
162 °C; mmax (CHCl3) cmꢀ1 1778 (OC@O) and 1704 (NC@O); dH
(400 MHz; CDCl3) 7.66 (2H, br d, J 7.3, 2 ꢁ CH; Ar), 7.49–7.38
(3H, m, 3 ꢁ CH; Ph), 7.06–6.87 (12H, m, 12 ꢁ CH; 3 ꢁ Ph), 6.66
(2H, br d, J 7.3, Ar), 6.28 (1H, s, CHN), 5.00 (1H, q, J 7.0, ArCHCH3),
2.44 (2H, dd, J 7.2 and 1.6 CH2Ar), 1.91–1.79 (1H, m (appears as a
septet J ꢂ 6.8), (CH3)2CH), 1.37 (3H, d, J 7.0, ArCHCH3), 0.92 (3H,
d, J 6.6, CHACHCHB) and 0.91 (3H, d, J 6.6, CHACHCHB); dC
4.11. Parallel kinetic resolution of pentafluorophenyl
2-phenylbutanoate rac-8 using a quasi-enantiomeric
combination of 4-phenyloxazolidin-2-one (R)-1 and 4,5,5-
triphenyl oxazolidin-2-one (S)-6
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(0.28 mL, 2.5 M in hexane, 0.70 mmol), 4-phenyl-oxazolidin-2-one
(R)-1 (50 mg, 0.32 mmol), 4,5,5-triphenyl-oxazolidin-2-one (S)-6
(0.10 g, 0.32 mmol) and pentafluorophenyl 2-phenylbutanoate
rac-8 (0.209 g, 0.63 mmol) gave a mixture of two diastereoisomeric
oxazolidin-2-ones (S,R)-18 (ratio 99:1: syn-:anti-) and (R,S)-9 (ratio
97:3: syn-:anti-). The crude residue was purified by flash chroma-
tography on silica gel eluting with light petroleum ether (bp
40–60 °C)/diethyl ether (7:3) to give (2S,4R)-3-(2-phenylbuta-
noyl)-4-phenyl-oxazolidin-2-one (S,R)-syn-18 (62 mg, 63%) as a
white solid; mp 82–84 °C; Rf [light petroleum ether (bp 40–
3
3
3
3
(100 MHz; CDCl3) 173.5 (NC@O), 152.0 (OC@O), 141.8, 138.1 and
135.0 (3 ꢁ i-C; 3 ꢁ Ph), 140.5 (i-CCH2; Ar), 136.6 (i-C; Ar), 129.12,
128.92, 128.91, 128.02, 127.91, 127.82, 127.52, 127.43, 126.32, and
126.22 (19 ꢁ CH; 19 ꢁ Ph and Ar), 88.5 (CPh2O), 66.0 (CHN), 45.0
((CH3)2CH), 43.4 (ArCHCH3), 30.2 (CH2Ar), 22.4 (CHACHCHB), 22.3
60 °C)/diethyl ether (1:1)] 0.33; ½a D20
¼ þ77:4 (c 4.0, CHCl3); mmax
ꢃ
(CH2Cl2) cmꢀ1 1772 (OC@O) and 1700 (NC@O); dH (400 MHz;
CDCl3) 7.17–7.09 (6H, m, 6 ꢁ CH; Ph), 7.04–7.02 (2H, m, 2 ꢁ CH;
Ph), 6.81–6.79 (2H, m, 2 ꢁ CH; Ph), 5.38 (1H, dd, J 8.8 and 5.0,
CHN), 4.82 (1H, t, J 7.5, PhCHEt), 4.55 (1H, t, J 8.8, CHAHBO), 3.98
3
þ
3
(CHA3 CHCHB3) and 18.9 (ArCHCH3) (Found MNH4
C34H37N2O3 requires MNH4þ, 521.2799).
,
521.2796;

2230
E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
(1H, dd, J 8.8 and 5.0, CHAHBO), 2.01–1.90 (1H, ddq, J 13.5, 7.3 and
7.5, CHAHBCH3), 1.68–1.57 (1H, ddq, J 13.5, 7.3 and 7.5, CHAHBCH3)
and 0.84 (3H, t, J 7.5, CH3CH2); dC (100 MHz; CDCl3) 173.0 (NC@O),
153.1 (OC@O), 138.2 (i-C; PhA), 138.0 (i-CC; PhB), 128.82, 128.72,
128.41, 128.32, 127.11 and 125.62 (10 ꢁ CH; PhA and PhB), 69.4
(CH2O), 57.7 (CHN), 51.1 (PhCH), 26.2 (CH2CH3) and 11.9 (CH2CH3)
(Found MH+, 310.1437; C19H20NO3 requires MH+, 310.1443);
1780 (OC@O) and 1711 (NC@O); dH (400 MHz; CDCl3) 7.57 (2H,
br d, J 7.7, 2 ꢁ CH; Ph)2s, 7.40–7.30 (8H, m, 4 ꢁ CH; Ph)3s+5a
,
7.19–7.00 (10H, m, 10 ꢁ CH; Ph),5s+5a 6.95–6.70 (18H, m,
16 ꢁ CH; Ph),8s+10a 6.53 (2H, br d, J 7.7, 2 ꢁ CH; Ph),2s 6.19 (1H, s,
PhCHN),s 5.98 (1H, s, PhCHN),a 4.70 (1H, d, J 10.3, PhCHi-Pr),a
4.55 (1H, br d,
J
10.1, PhCHi-Pr),s 2.35–2.19 (2H, m,
2 ꢁ CH(CH3)2),s+a 0.77 (6H, d, J 6.9, 2 ꢁ CH3ACHCH3B),3s+3a 0.58 (3H,
d, J 6.9, CH3ACHCHB3)3a and 0.55 (3H, d, J 6.9, CH3ACHCH3B)3s; dC
(100 MHz; CDCl3) 173.7 (NC@O),a 172.8 (NC@O),s 152.6 (OC@O),a
152.3 (OC@O),s 141.6, 137.8, 136.9 and 134.9 (4 ꢁ i-C; 4 ꢁ Ph),4s
and
(2R,4S)-3-(2-phenylbutanoyl)-4,5,5-triphenyl-oxazolidin-2-
one (R,S)-syn-9 (86 mg, 59%, 94% de) as a white powder; Rf [light
petroleum (bp 40–60 °C)/diethyl ether (1:1)] 0.63; mp 150–
153 °C; ½a 2D0
ꢃ
¼ ꢀ195:2 (c 3.4, CHCl3); mmax (CHCl3) cmꢀ1 1780
141.3, 137.6, 136.6 and 136.0 (4 ꢁ i-C; 4 ꢁ Ph),4a 129.32s, 128.91s
,
,
(NC@O) and 1707 (OC@O); dH (400 MHz; CDCl3) 7.57 (2H, br d, J
7.5, 2 ꢁ CH; Ph), 7.41–7.30 (3H, m, 3 ꢁ CH; Ph), 7.16–7.05 (5H,
m, 5 ꢁ CH; Ph), 6.94–6.79 (8H, m, 8 ꢁ CH; 3 ꢁ Ph), 6.57 (2H, br d,
J 7.5, Ph), 6.20 (1H, s, CHN), 4.72 (1H, t, J 7.3, ArCHEt), 19.7–1.85
(1H, m, CHAHBCH3), 1.69–1.57 (1H, m, CHAHBCH3) and 0.70 (3H, t,
J 7.3, CH3CHAHB); dC (100 MHz; CDCl3) 172.8 (OC@O), 152.1
(NC@O), 141.7, 138.0 and 135.0 (3 ꢁ i-C; 3 ꢁ Ph), 137.7 (i-C;
PhCHEt), 128.93, 128.82, 128.32, 127.92, 127.81, 127.52, 127.41,
127.32, 127.11, 126.32 and 126.22 (20 ꢁ CH; 4 ꢁ Ph), 88.6 (CPh2O),
65.9 (CHN), 51.1 (ArCHEt), 26.7 (CH2CH3) and 11.8 (CH2CH3)
(Found MH+, 462.2062; C31H28NO3 requires MH+, 462.2064); m/z
416 (20%, M+), 315 (10, MHꢀArCHCH3C@NH+), 256 (40,
PhCHCPh2þ), 183 (50, Ph2C@OH+), 146 (40, ArCHCH3C@NH+), 119
(70, PhCHEt+), 91 (100, PhCH2þ), and 77 (20, Ph+).
128.82s, 128.22s, 127.92s, 127.7,1s 127.52s, 127.41s, 127.11s, 127.02s
126.32s and 126.42s (20 ꢁ CH; 4 ꢁ Ph),20s 129.3,2a 128.9,1a
128.62a
, , , , , ,
128.51a 128.32a 128.22a 128.01a 127.6,2a 127.52a
127.1,1a 126.42a and 125.92a (20 ꢁ CH; 4 ꢁ Ph),20a 88.7 (CPh2O),1a
88.6 (CPh2O),1s 66.6 (CHN),1a 65.8 (CHN),1s 56.7 (PhCHi-Pr),1s
56.1 (PhCHi-Pr),1a 31.6 (CH(CH3)2)1a, 31.5 (CH(CH3)2)1s, 21.43a
,
21.33s, 20.03a and 20.03s (4 ꢁ CH3)6s+6a (Found MNH4þ, 493.2490;
C32H33N2O3 requires MNH4þ, 493.2486).
4.13. Parallel kinetic resolution of pentafluorophenyl
2-(4-methylphenyl)propionate rac-12 using a quasi-
enantiomeric combination of 4-phenyloxazolidin-2-one (R)-1
and 4,5,5-triphenyl oxazolidin-2-one (S)-6
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(0.28 mL, 2.5 M in hexane, 0.70 mmol), 4-phenyl-oxazolidin-2-
one (R)-1 (50 mg, 0.32 mmol), 4,5,5-triphenyl-oxazolidin-2-one
(S)-6 (0.10 g, 0.32 mmol) and pentafluorophenyl 2-(4-methyl-
phenyl)propionate rac-12 (0.209 g, 0.63 mmol) gave a mixture of
two diastereoisomeric oxazolidin-2-ones (S,R)-20 (ratio 99:1: syn-
:anti-) and (R,S)-13 (ratio 98:2: syn-:anti-). The crude residue was
purified by flash chromatography on silica gel eluting with light
petroleum ether (bp 40–60 °C)/diethyl ether (7:3) to give (2S,4R)-
3-[(4-methylphenyl)propionyl]-4-phenyl-oxazolidin-2-one (S,R)-
syn-20 (44 mg, 45%) as a white solid; Rf [light petroleum ether
(bp 40–60 °C)/diethyl ether (1:1)] 0.36; mp 105–110 °C {for (R,S)-
syn-20; mp 105–110 °C}; mmax (CHCl3) cmꢀ1 1780 (OC@O) and
4.12. Parallel kinetic resolution of pentafluorophenyl 2-phenyl-
3-methylbutanoate rac-10 using a quasi-enantiomeric
combination of 4-phenyloxazolidin-2-one (R)-1 and 4,5,5-
triphenyl oxazolidin-2-one (S)-6
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(0.28 mL, 2.5 M in hexane, 0.70 mmol), 4-phenyl-oxazolidin-2-one
(R)-1 (50 mg, 0.32 mmol), 4,5,5-triphenyl-oxazolidin-2-one (S)-6
(0.10 g, 0.32 mmol) and pentafluorophenyl 2-phenyl-3-methylbut-
anoate rac-10 (0.22 g, 0.63 mmol) gave a mixture of two diastereo-
isomeric oxazolidin-2-ones (S,R)-19 (ratio 77:23: syn-:anti-) and
(R,S)-11 (ratio 88:12: syn-:anti-). The crude residue was purified
by flash chromatography on silica gel eluting with light petroleum
ether (bp 40–60 °C)/diethyl ether (7:3) to give (2S,4R)-3-(2-phen-
1700 (NC@O); ½a 2D0
¼ þ121:6 (c 0.6, CHCl3) {for (R,S)-syn-20;
ꢃ
½
a 2D0
ꢃ
¼ ꢀ116:5 (c 0.8, CHCl3)}; dH (400 MHz, CDCl3) 7.21–7.12 (3H,
yl-3-methylbutanoyl)-4-phenyl-oxazolidin-2-one
(S,R)-syn-19
m, 3 ꢁ CH; Ph), 6.96 (2H, d, J 8.2, 2 ꢁ CH; Ar), 6.90 (2H, d, J 8.2,
2 ꢁ CH; Ar), 6.86 (2H, d, J 6.9, 2 ꢁ CH; Ph), 5.36 (1H, dd, J 9.1 and
5.1, CHN), 5.01 (1H, q, J 6.9, ArCHCH3), 4.54 (1H, t, J 9.1, CHAHBO),
3.99 (1H, dd, J 9.1 and 5.1, CHAHBO), 2.24 (3H, s, CH3; Ar) and 1.32
(3H, d, J 6.9, ArCHCH3); dC (100 MHz, CDCl3) 173.5 (NC@O), 154.9
(OC@O), 138.4 (i-CMe; Ar), 136.8 (i-C; Ar), 136.4 (i-C; Ph), 129.12,
128.62, 128.41, 127.62 and 125.72 (9 ꢁ CH; Ph and Ar), 69.6
(CH2O), 57.8 (CHN), 43.2 (ArCHCH3), 21.0 (CH3; Ar) and 18.7
(80 mg, 79%, 54% de) as a white solid; Rf [light petroleum ether
(bp 40–60 °C)/diethyl ether (1:1)] 0.40; mp 80–92 °C;
½
a 2D5
ꢃ
¼ þ1:3 (c 3.0, CHCl3); mmax (CHCl3) cmꢀ1 1781 (OC@O) and
1780 (NC@O); dH (400 MHz; CDCl3) 7.40–7.10 (18H, m, 8 ꢁ CH;
2 ꢁ Phs and 10 ꢁ CH; 2 ꢁ Pha), 6.77 (2H, d, J 7.3, 2 ꢁ CH; Phs),
5.46 (1H, dd, J 8.9 and 4.7, PhCHNs), 5.33 (1H, dd, J 8.8 and 3.7,
PhCHNa), 4.76 (1H, d, J 10.7, PhCHi-Pra), 4.66 (1H, d, J 10.7,
PhCHi-Prs), 4.64 (1H, t, J 8.8, CHAHBOs), 4.48 (1H, t, J 8.8, CHAHBOa),
4.21 (1H, dd, J 8.8 and 3.7, CHAHBO), 4.05 (1H, dd, J 8.8 and 4.7,
CHAHBO), 2.40–2.30 (2H, m, 2 ꢁ CH(CH3)2),s+a 1.04 (3H, d, J 6.9,
CH3ACHCH3B),s 0.76 (3H, d, J 6.9, CH3ACHCH3B)a, 0.58 (3H, d, J 6.9,
CHA3 CHCHB3)s and 0.55 (3H, d, J 6.9, CHA3 CHCH3B)a; dC (100 MHz;
CDCl3) 173.8 (NC@O),a 172.9 (NC@O),s 153.4 (OC@O),a 153.2
(OC@O),s 139.4 (i-C; Ph),a 138.2 (i-C; Ph),s 137.9 (i-C; Ph),a 137.1
(i-C; Ph),s 129.3,2a 128.9,1a 128.6,1a 128.3,2a 127.32a and 125.82a
(10 ꢁ CH; 2 ꢁ Ph),10a 129.2,2s 128.8,2s 128.3,2s 128.3,1s 127.21s
and 125.32s (10 ꢁ CH; 2 ꢁ Ph),10s 69.4 (CH2O),s 69.3 (CH2O),a 57.9
(PhCHN),a 57.6 (PhCHN),s 56.9 (PhCHi-Pr),s 55.9 (PhCHi-Pr),a 32.8
(CH(CH3)2),a 30.7 (CH(CH3)2),s 21.6 (CH3ACHCHB3),s 21.2
(CH3ACHCH3B),a 20.1 (CH3ACHCH3B),a and 20.0 (CH3ACHCHB3)s (Found
þ
þ
(ArCHCH3) (Found MNH4
,
327.1701; C19H23N2O3
requires
MNH4þ, 327.1709); and (2R,4S)-3-[2-(4-methylphenyl)propionyl]-
4,5,5-triphenyl-oxazolidin-2-one (R,S)-syn-13 (75 mg, 51%, 96%
de) as a white powder; Rf [light petroleum ether (bp 40–60 °C)/
diethyl ether (1:1)] 0.58; mp 119–121 °C; ½a D20
¼ ꢀ258:6 (c 2.4,
ꢃ
CHCl3); mmax (CHCl3) cmꢀ1 1780 (OC@O) and 1703 (NC@O); dH
(400 MHz; CDCl3) 7.64 (2H, br d, J 7.7, 2 ꢁ CH; Ar), 7.48–7.38 (3H,
m, 3 ꢁ CH; Ph), 7.04–6.89 (12H, m, 12 ꢁ CH; Ph), 6.69 (2H, br d, J
7.7, Ar), 6.26 (1H, s, CHN), 4.95 (1H, q, J 7.0, ArCHCH3), 2.32 (3H, s,
CH3Ar) and 1.35 (3H, d, J 7.0, ArCHCH3); dC (100 MHz; CDCl3)
173.4 (NC@O), 152.0 (OC@O), 141.8, 138.0 and 135.1 (3 ꢁ i-C;
3 ꢁ Ph), 136.6 and 136.5 (2 ꢁ i-C; 3 ꢁ Ar), 129.12, 128.92, 128.91,
128.12, 127.93, 127.52, 127.42, 127.31, 126.32 and 126.12 (19 ꢁ CH;
3 ꢁ Ph and Ar), 88.5 (CPh2O), 66.0 (CHN), 44.6 (ArCHCH3), 21.1
(CH3Ar) and 19.1 (ArCHCH3) (Found MH+, 462.2068; C31H28NO3 re-
quires MH+, 462.2064); m/z 461 (15%, M+), 315 (5, MH+ꢀArCH-
CH3CO), 256 (40, PhCHCPh2þ), 183 (10, Ph2 C@OH+), 146 (80,
ArCHCH3C@NH+), 119 (100, ArCHCH3þ) and 77 (20, Ph+).
þ
þ
þ
MNH4
, 341.1864; C20H25N2O3 requires MNH4 , 341.1860);
and (2R,4S)-3-(2-phenyl-3-methylbutanoyl)-4,5,5-triphenyl-oxaz-
olidin-2-one (R,S)-syn-11 (65 mg, 43%, 76% de) as a white solid;
Rf [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.71;
mp 170–178 °C; ½a D25
ꢃ
¼ ꢀ270:9 (c 2.6, CHCl3); mmax (CHCl3) cmꢀ1

E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
2231
4.14. Parallel kinetic resolution of pentafluorophenyl
2-(4-chlorophenyl)propionate rac-14 using a quasi-
enantiomeric combination of 4-phenyloxazolidin-2-one (R)-1
and 4,5,5-triphenyl oxazolidin-2-one (S)-6
(NC@O); dH (400 MHz; CDCl3) 7.28–7.15 (3H, m, 3 ꢁ CH; Ph),
7.00 (4H, m, 4 ꢁ CH, Ph and Ar), 6.90 (2H, dt, J 7.9 and 1.9,
2 ꢁ CH; Ar), 5.44 (1H, dd J 9.2 and 5.2, CHN), 5.09 (1H, q, J 6.9,
ArCHCH3), 4.63 (1H, t, J 9.0, CHAHBO), 4.06 (1H, dd, J 9.0 and 5.2,
CHAHBO), 2.43 (2H, d, J 7.4, CH2Ar), 1.89–1.79 (1H, m, (CH(CH3)2),
1.38 (3H, d, J 6.9, ArCHCH3), 0.90 (3H, d, J 6.6, CHACHCHB) and
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(0.28 mL, 2.5 M in hexane, 0.70 mmol), 4-phenyl-oxazolidin-2-one
(R)-1 (50 mg, 0.32 mmol), 4,5,5-triphenyl oxazolidin-2-one (S)-6
(0.10 g, 0.32 mmol) and pentafluorophenyl 2-(4-chlorophenyl)pro-
pionate rac-14 (0.22 g, 0.63 mmol) gave a mixture of two diaste-
reoisomeric oxazolidin-2-ones (S,R)-21 (ratio 93:7: syn-:anti-)
and (R,S)-15 (ratio 96:4: syn-:anti-). The crude residue was purified
by flash chromatography on silica gel eluting with light petroleum
ether (bp 40–60 °C)/diethyl ether (7:3) to give (2S,4R)-3-[(4-chloro-
phenyl)propionyl]-4-phenyl-oxazolidin-2-one (S,R)-syn-21 (74 mg,
71%) as a white solid; Rf [light petroleum ether (bp 40–60 °C)/
diethyl ether (1:1)] 0.27; mp 142–145 °C {for (R,S)-syn-21; mp
142–144 °C}; mmax (CHCl3) cmꢀ1 1782 (OC@O) and 1700 (NC@O);
3
3
0.89 (3H, d, J 6.6, CHACHCHB); dC (100.6 MHz; CDCl3) 174.3
3
3
(NC@O), 153.3 (OC@O), 140.7 (i-C; Ar), 139.4 (i-C; Ar), 137.4 (i-C;
Ph), 129.32 and 127.02 (4 ꢁ CH; Ar), 129.2,1 128.72 and 125.82
(5 ꢁ CH; Ph), 69.7 (CH2O), 58.1 (CHN), 45.1 (CH(CH3)2), 42.7
(ArCHCH3), 30.2 (CH2Ar), 22.42 (CH3)2CH) and 19.4 (CH3CH2)
(Found MH+, 352.1909; C22H26NO3 requires MH+, 352.1907); m/z
351.1 (10% M+), 188.1 (10, Ar(CH3)C@C@O+), 161.1 (10, Ar+CHCH3),
145.1 (100, ArCH2þ) and 77.1 (10, Ph+) (Found MNH4þ, 369.2171;
C22H29N2O3 requires MNH4þ, 369.2173); and (2R,4S)-3-[(4-isobu-
tylphenyl)propionyl]-4,5,5-triphenyl-oxazolidin-2-one (R,S)-syn-
17 (88 g, 55%, 96% de) as a white powder; Rf [light petroleum ether
(bp 40–60 °C)/diethyl ether (1:1)] 0.63; mp 62–64 °C;
½
a 2D0
ꢃ
¼ þ144:4 (c 1.6, CHCl3) {for (R,S)-syn-21; ½a D20
ꢃ
¼ ꢀ142:4 (c
½
a 2D5
ꢃ
¼ ꢀ306:7 (c 4.4, CHCl3); mmax (CHCl3) cmꢀ1 1778 (OC@O)
1.5, CHCl3)}; dH (400 MHz, CDCl3) 7.32–7.22 (3H, m, 3 ꢁ CH; Ph),
7.18 (2H, dt, J 8.5 and 2.2, 2 ꢁ CH; Ar), 7.01 (2H, dt, J 8.5 and 2.2,
2 ꢁ CH; Ar), 6.95 (2H, dt, J 6.8 and 1.5, 2 ꢁ CH; Ph), 5.45 (1H, dd,
J 9.0 and 4.8, CHN), 5.06 (1H, q, J 6.8, ArCHCH3), 4.65 (1H, t, J 9.0,
CHAHBO), 4.13 (1H, dd, J 9.0 and 4.8, CHAHBO) and 1.37 (3H, d, J
6.8, ArCHCH3); dC (100 MHz, CDCl3) 173.8 (NC@O), 152.8 (OC@O),
138.2 (i-CC; Ar), 133.2 (i-C; Ar), 132.8 (i-CCl; Ar), 129.72, 128.82,
128.63 and 125.62 (9 ꢁ CH; 2 ꢁ Ar), 69.4 (CH2O), 57.9 (CHN), 43.8
(ArCHCH3) and 18.9 (ArCHCH3) (Found Mð35ClÞNH4þ, 347.1154;
C18H20ClN2O3 requires Mð35ClÞNH4þ, 347.1157); and (2R,4S)-3-
and 1704 (NC@O); dH (400 MHz; CDCl3) 7.66 (2H, br d, J 7.3,
2 ꢁ CH; Ar), 7.49–7.38 (3H, m, 3 ꢁ CH; Ph), 7.06–6.87 (12H, m,
12 ꢁ CH; 3 ꢁ Ph), 6.66 (2H, br d, J 7.3, Ar), 6.28 (1H, s, CHN), 5.00
(1H, q, J 7.0, ArCHCH3), 2.44 (2H, dd, J 7.2 and 1.6 CH2Ar), 1.91–
1.79 (1H, m (appears as a septet J ꢂ 6.8), (CH3)2CH), 1.37 (3H, d, J
7.0, ArCHCH3), 0.92 (3H, d, J 6.6, CHACHCHB) and 0.91 (3H, d, J
3
3
6.6, CHA3 CHCH3B); dC (100 MHz; CDCl3) 173.5 (NC@O), 152.0
(OC@O), 141.8, 138.1 and 135.0 (3 ꢁ i-C; 3 ꢁ Ph), 140.5 (i-CCH2;
Ar), 136.6 (i-C; Ar), 129.12, 128.92, 128.91, 128.02, 127.91, 127.82,
127.52, 127.43, 126.32, and 126.22 (19 ꢁ CH; 19 ꢁ Ph and Ar),
88.5 (CPh2O), 66.0 (CHN), 45.0 ((CH3)2CH), 43.4 (ArCHCH3), 30.2
(CH2Ar), 22.4 (CHACHCHB), 22.3 (CHACHCHB) and 18.9 (ArCHCH3)
[(4-chlorophenyl)propionyl]-4,5,5-triphenyl
oxazolidin-2-one
(R,S)-syn-15 (91 mg, 60%, 92% de) as a white solid; Rf [light petro-
3
3
3
3
þ
þ
leum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.60; mp 100–
(Found MNH4
,
521.2800; C34H37N2O3 requires MNH4 ,
102 °C; ½a 2D0
ꢃ
¼ ꢀ296:2 (c 3.4, CHCl3); mmax (CHCl3) cmꢀ1 1780
521.2799); m/z 503 (40%, M+), 459 (10, M+ꢀCO2), 315 (10,
MHꢀArCHCH3C@NH+), 256 (90, PhCHCPh2þ), 188 (100, ArCH-
CH3C@NH+), 161 (90, ArCHCH3þ) and 77 (20, Ph+).
(OC@O) and 1706 (NC@O); dH (400 MHz; CDCl3) 7.58 (2H, br d, J
7.7, 2 ꢁ CH; Ph), 7.40–7.30 (3H, m, 3 ꢁ CH; Ph), 7.10 (2H, dt, J 8.2
and 1.9, 2 ꢁ CH; Ar), 6.94 (2H, dt, J 8.2 and 1.9, 2 ꢁ CH; Ar),
6.99–6.82 (8H, m, 8 ꢁ CH; Ph), 6.60 (2H, br d, J 7.2, Ph), 6.19 (1H,
s, CHN), 4.90 (1H, q, J 7.0, ArCHCH3), 1.28 (3H, d, J 7.0, ArCHCH3);
dC (100 MHz; CDCl3) 172.8 (NC@O), 151.9 (OC@O), 141.8, 138.0,
137.9, 134.9 and 132.8 (5 ꢁ i-C; 3 ꢁ Ph and 2 ꢁ Ar), 129.62,
128.92, 128.91, 128.52, 128.01, 127.92, 127.62, 127.41, 127.42,
126.12 and 126.02 (19 ꢁ CH; 3 ꢁ Ph and Ar), 88.6 (CPh2O),
65.9 (CHN), 43.3 (ArCHCH3) and 18.9 (ArCHCH3) (Found
4.16. Parallel kinetic resolution of 4,5,5-triphenyl oxazolidin-2-
one rac-6 using a quasi-enantiomeric combination of
pentafluorophenyl 2-(6-methoxynaphthalen-2-yl)propionate
(S)-23 and pentafluorophenyl 2-phenylbutanoate (R)-8
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(60
one rac-6 (42 mg, 0.13 mmol), pentafluorophenyl 2-(6-meth-
oxynaphthalen-2-yl)propionate (S)-23 (26 mg, 67 mol) and pen-
tafluorophenyl 2-phenylbutanoate (R)-8 (22 mg, 67 mol) gave a
lL, 2.5 M in hexane, 0.15 mmol), 4,5,5-triphenyl-oxazolidin-2-
þ
þ
Mð35ClÞNH4
,
499.1786; C30H28ClN2O3 requires Mð35ClÞNH4
,
499.1783) (Found M(35Cl)H+, 482.1517; C30H25ClNO3 requires
M(35Cl)H+, 482.1525).
l
l
mixture of two diastereoisomeric oxazolidin-2-ones (S,R)-24 (ratio
96:4: syn-:anti-) and (R,S)-9 (ratio 96:4: syn-:anti-). The crude res-
idue was purified by flash chromatography on silica gel eluting
with light petroleum ether (bp 40–60 °C)/diethyl ether (7:3) to
4.15. Parallel kinetic resolution of pentafluorophenyl
2-(4-isobutylphenyl)propionate rac-16 using a quasi-
enantiomeric combination of 4-phenyloxazolidin-2-one (R)-1
and 4,5,5-triphenyl oxazolidin-2-one (S)-6
give
(2S,4R)-3-[2-(6-methoxynaphth-2-yl)-propionyl]-4,5,5-tri-
phenyl-oxazolidin-2-one (S,R)-syn-24 (15 mg, 43%, 92% de) as a
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(0.28 mL, 2.5 M in hexane, 0.70 mmol), 4-phenyl-oxazolidin-2-one
(R)-1 (50 mg, 0.32 mmol), 4,5,5-triphenyl-oxazolidin-2-one (S)-6
(0.10 g, 0.32 mmol) and pentafluorophenyl 2-(4-isobutyl-
phenyl)propionate rac-16 (0.235 g, 0.63 mmol) gave a mixture of
two diastereoisomeric oxazolidin-2-ones (S,R)-22 (ratio 97:3:
syn-:anti-) and (R,S)-17 (ratio 98:2: syn-:anti-). The crude residue
was purified by flash chromatography on silica gel eluting with
light petroleum ether (bp 40–60 °C)/diethyl ether (7:3) to give
(2S,4R)-3-[2-(4-isobutylphenyl)propionyl]-4-phenyl-oxazolidin-2-
one (S,R)-syn-22 (67 mg, 60%) as a white solid; mp 86–88 °C; Rf
[light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.39;
white solid; Rf [light petroleum ether (bp 40–60 °C)/diethyl ether
(1:1)] 0.53; ½a 2D5
¼ þ302:5 (c 1.2, CHCl3) mp 106–110 °C; mmax
ꢃ
(CHCl3) cmꢀ1 1781 (OC@O) and 1710 (NC@O); dH (400 MHz;
CDCl3) 7.60–7.51 (3H, m, 3 ꢁ CH; Ar and Ph), 7.41–7.33 (4H, m,
4 ꢁ CH; Ar and/or Ph), 7.23 (1H, br s, CH; Ar), 7.20 (1H, dd, J 8.4
and 1.8, CH; Ar and/or Ph), 7.05–7.01 (2H, m, 2 ꢁ CH; Ar and/or
Ph), 6.90 (1H, d, J 7.9, CH; Ar or Ph), 6.88–6.81 (5H, m, 5 ꢁ CH;
Ar and Ph), 6.70 (2H, t, J 7.9, 2 ꢁ CH; Ar), 6.58 (2H, d, J 7.3,
2 ꢁ CH; Ar), 6.22 (1H, s, PhCH), 5.05 (1H, br q, J 7.0, ArCHCH3),
3.85 (3H, s, CH3O) and 1.36 (3H, d, J 7.0, ArCHCH3); dC (100 MHz;
CDCl3) 173.2 (NC@O), 157.6 (i-CO; Ar), 151.8 (OC@O), 141.8,
138.0, 135.0, 134.9 133.6 and 128.7 (6 ꢁ i-C; Ar and Ph), 129.4,
127.0, 126.3, 126.2, 118.6 and 105.5 (6 ꢁ CH; Ar), 128.9,2 128.8,1
127.9,2 127.5,2 127.4,2 127.4,1 127.3,1 126.22 and 126.12
½
a 2D5
ꢃ
¼ þ118:7 (c 6.0, CHCl3) {for (R,S)-syn-22; lit. ½a D25
¼ ꢀ114:6
ꢃ
(c 4.2, CHCl3);19 mmax (CHCl3) cmꢀ1 1779 (OC@O) and 1705

2232
E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
(15 ꢁ CH; 3 ꢁ Ph), 88.5 (Ph2CO), 66.0 (PhCHN), 55.3 (CH3O), 44.0
(ArCHCH3) and 19.1 (ArCHCH3) (Found M+, 527.2085; C35H29NO4
requires M+, 527.2091); and (2R,4S)-3-(2-phenyl-butanoyl)-4,5,5-
triphenyl-oxazolidin-2-one (R,S)-syn-9 (18 mg, 57%, 92% de) as a
white solid; Rf [light petroleum ether (bp 40–60 °C)/diethyl ether
(1:1)] 0.66; which was found to be spectroscopically identical to
that obtained previously.
7.0, PhCHCH3) and 1.35 (3H, d, J 7.0, PhCHCH3); dC (100 MHz;
CDCl3) 173.2 (NC@O), 152.0 (OC@O), 141.8, 138.0 and 135.0
(3 ꢁ i-C; 3 ꢁ Ph–oxazolidin-2-one), 139.5 (i-C; Ph), 128.92, 128.81,
128.42, 128.32, 127.93, 127.62, 127.51, 127.42, 127.01, 126.22 and
126.12 (20 ꢁ CH; 4 ꢁ Ph), 88.5 (CPh2O), 66.0 (CHN), 44.0
(PhCHCH3) and 19.0 (PhCHCH3) (Found MNa+, 448.1912;
C24H31NO4SiNa requires MNa+, 448.1915); m/z 447 (10%, M+),
315 (5, M+ꢀPh(CH3)C@C@O), 256 (15, PhCHCPh2þ), 183 (20,
Ph2C@OH+), 105 (100, PhCH@NH+) and 77 (20, Ph+); and the pen-
tafluorophenyl 2-phenylpropionate (S)-3 (0.18 g, 36%) as a colour-
less oil; Rf [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)]
4.17. Parallel kinetic separation of 4-phenyl-oxazolidin-2-one
(R)-1 and 4,5,5-triphenyl oxazolidin-2-one (S)-6 using a quasi-
enantiomeric combination of pentafluorophenyl 2-(6-
methoxynaphthalen-2-yl)propionate (S)-23 and
0.83;
½
a 2D0
ꢃ
¼ þ47:21 (c 7.6, CHCl3); ꢂ63% ee {lit.20 (S)-3;
pentafluorophenyl 2-phenylbutanoate (R)-8
½
a 2D0
CHCl3)}.
ꢃ
¼ þ74:5 (c 4.9, CHCl3); lit.19 (R)-3; ½a D20
¼ ꢀ75:0 (c 3.3,
ꢃ
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(0.24 mL, 2.5 M in hexane, 0.60 mmol), 4-phenyl-oxazolidin-2-one
(R)-1 (0.43 g, 0.27 mmol), 4,5,5-triphenyl-oxazolidin-2-one (S)-6
(0.86 g, 0.27 mmol), pentafluorophenyl 2-(6-methoxynaphthalen-
2-yl)propionate (S)-23 (0.11 g, 0.27 mmol) and pentafluorophenyl
2-phenylbutanoate (R)-8 (90 mg, 0.27 mmol) gave a mixture of
two diastereoisomeric oxazolidin-2-ones (S,R)-25 (ratio >95:5:
syn-:anti-) and (R,S)-9 (ratio >95:5: syn-:anti-). The crude residue
was purified by flash chromatography on silica gel eluting with
light petroleum ether (bp 40–60 °C)/diethyl ether (7:3) to give
(2 S,4 R)-3-[2-(6-methoxynaphth-2-yl)-propionyl]-4-oxazolidin-2-
one (S,R)-syn-25 (49 mg, 48%) as a white solid; Rf [light petroleum
4.19. Mutual kinetic resolution of 4,5,5-triphenyl oxazolidin-2-
one rac-6 and oxazolidin-2-one 26 using pentafluorophenyl 2-
phenylpropionate rac-3
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(0.41 mL, 2.5 M in hexane, 1.26 mmol), 4,5,5-triphenyl-oxazolidin-
2-one rac-6 (0.181 g, 0.57 mmol), oxazolidin-2-one 26 (50 mg,
0.57 mmol) and pentafluorophenyl 2-phenylpropionate rac-6
(0.363 g, 1.15 mmol) gave a mixture of two diastereoisomeric
oxazolidin-2-ones rac-syn- and anti-7 (ratio 95:5: syn-:anti-) and
rac-27 (ratio 7:27: 39:61). The crude residue was purified by flash
chromatography on silica gel eluting with light petroleum ether
(bp 40–60 °C)/diethyl ether (7:3) to give (2RS,4SR)-3-(2-phenylpro-
pionyl)-4,5,5-triphenyl-oxazolidin-2-one (RS,SR)-rac-syn-7 (95 mg,
37%, 90% de) as a white powder; Rf [light petroleum ether (bp
40–60 °C)/diethyl ether (1:1)] 0.83; which was spectroscopically
identical to that obtained previously; and 3-(2-phenylpropionyl)-
oxazolidin-2-one rac-27 (79 mg, 63%) as a colourless oil; Rf [light
petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.14; mmax
(CHCl3) cmꢀ1 1772 (OC@O) and 1700 (NC@O); dH (400 MHz;
CDCl3) 7.37 (2H, dt, J 7.1 and 1.5, 2 ꢁ CH; Ph), 7.31 (2H, br ddd, J
7.1, 1.5 and 1.0, 2 ꢁ CH; Ph), 7.27–7.22 (1H, br tt, J 7.1 and 1.5,
CH; Ph), 5.11 (1H, q, J 7.0, CHCH3), 4.42–4.25 (2H, m, CH2O),
4.11–4.02 (1H, ABq, CHAHBN), 3.97–3.89 (1H, ABq, CHAHBN) and
1.50 (3H, d, J 7.0, CH3); dC (100 MHz; CDCl3) 174.4 (NC@O), 152.9
(OC@O), 140.2 (i-C; Ph), 128.42, 129.02 and 127.01 (5 ꢁ CH; Ph),
61.6 (CH2O), 42.7 (CH2N), 42.6 (CHCH3) and 19.2 (CH3) (Found
M+, 219.0888; C12H13NO3 requires M+, 219.0890); m/z 219 (3%,
M+), 132 (10, PhCH3C@C@O+), 105 (55, PhCH3CH+), 104 (50,
PhCHCH2þ), 77 (95, C6H5þ) and 43 (100, NHCO+).
(40–60 °C)/diethyl
ether
(1:1)]
0.33;
mp
168–170 °C;
½
a 2D0
ꢃ
¼ þ207:5 (c 0.8, CHCl3); mmax (CHCl3) cmꢀ1 1780 (OC@O)
and 1699 (NC@O); dH (400 MHz; CDCl3) 7.60 (1H, d, J 8.4,
1 ꢁ CH; Ar), 7.51 (1H, d, J 8.4, 1 ꢁ CH; Ar), 7.33 (1H, s, CH; Ar),
7.29–7.09 (6H, m, 6 ꢁ CH; Ar and Ph), 6.90 (2H, d, J 7.1, 2 ꢁ CH;
Ar and Ph), 5.46 (1H, dd, J 8.9 and 5.2, PhCHN), 5.20 (1H, q, J 6.9,
ArCHCH3), 4.60 (1H, t, J 9.1, CHAHBO), 4.03 (1H, dd J 8.9 and 5.2,
CHAHBO), 3.92 (3H, s, CH3O) and 1.44 (3H, d, J 6.9, ArCHCH3); dC
(100 MHz; CDCl3) 173.6 (NC@O), 157.6 (i-CO; Ar), 153.0 (OC@O),
138.2, 135.1, 133.6 and 128.8 (4 ꢁ i-C; Ar and Ph), 129.4, 127.0,
126.4, 126.3, 118.7 and 105.5 (6 ꢁ CH; Ar), 128.82, 127.21 and
125.92 (5 ꢁ CH; Ph), 69.5 (CH2O), 57.8 (PhCHN), 55.3 (CH3O), 43.8
(ArCHCH3) and 18.7 (ArCHCH3) (Found MH+, 376.1553;
C23H22NO4 requires MH+, 376.1543); and (2R,4S)-3-(2-phenyl-
butanoyl)-4,5,5-triphenyl-oxazolidin-2-one (R,S)-syn-9 (84 mg,
67%, >90% de) as a white solid; Rf [light petroleum ether (bp 40–
60 °C)/diethyl ether (1:1)] 0.66; which was found to be spectro-
scopically identical to that obtained previously.
4.18. Kinetic resolution of pentafluorophenyl 2-phenyl-
propionate rac-3 using 4,5,5-triphenyl oxazolidin-2-one (S)-6
4.20. Synthesis of 2-phenylpropionic acid (S)-28: hydrolysis of
oxazolidin-2-one (S,R)-syn-4
In the same way as oxazolidin-2-one rac-syn-7, n-butyl lithium
(0.32 mL, 2.5 M in hexane, 0.79 mmol), 4,5,5-triphenyl-oxazolidin-
2-one (S)-6 (0.249 g, 0.79 mmol) and pentafluorophenyl 2-phenyl-
propionate rac-3 (0.50 g, 1.60 mmol), gave after purification by col-
umn chromatography on silica gel eluting with light petroleum
ether (bp 40–60 °C)/diethyl ether (7:3) an inseparable diastereo-
isomeric mixture of oxazolidin-2-ones (R,S)-syn- and (S,S)-anti-7
(ratio 85:15: syn-:anti-). The crude residue was purified by flash
chromatography on silica gel eluting with light petroleum ether
(bp 40–60 °C)/diethyl ether (7:3) to give (2R,4S)-3-(2-phenylpropi-
onyl)-4,5,5-triphenyl-oxazolidin-2-one (R,S)-syn-7 (0.265 g, 75%,
70% de) as a white powder; Rf [light petroleum ether (bp 40–
Lithium hydroxide monohydrate (0.34 g, 8.02 mmol) was
slowly added to a stirred solution of oxazolidin-2-one (R,S)-syn-4
(1.34 g, 4.01 mmol) and hydrogen peroxide (2.27 mL, 8.02 mmol,
40%/w) in THF/water (3:1; 32 mL). The reaction mixture was stir-
red at room temperature for 12 h. The reaction mixture was
quenched with water (10 mL) and extracted with dichloromethane
(3 ꢁ 10 mL). The combined organic layers were dried over MgSO4
and were evaporated under reduced pressure to give the recovered
oxazolidin-2-one (R)-1 (0.62 g, 95%) as a white solid; ½a D20
¼ ꢀ48:3
ꢃ
(c 2.0, CHCl3), {for (S)-1; lit.18
½
a 2D0
ꢃ
¼ þ49:5 (c 2.1, CHCl3; for (R)-1;
lit.21
½
a 2D6
ꢃ
¼ ꢀ40:9 (c 3.0, CHCl3) and ½a D26
¼ ꢀ55:5 (c 3.8, EtOH)};
ꢃ
60 °C)/diethyl ether (1:1)] 0.60; mp 154–156 °C; ½a D20
ꢃ
¼ ꢀ255:1 (c
and 2-phenylpropionic acid (+)-(S)-28 (0.55 g, 91%) as colourless
3.4, CHCl3); mmax (CHCl3) cmꢀ1 1780 (OC@O) and 1704 (NC@O);
dH (400 MHz; CDCl3) 7.63 (2H, br d, J 7.7, 2 ꢁ CH; Ph), 7.46–7.36
(4H, m, 4 ꢁ CH; Ph), 7.19 (2H, br dd, J 5.0, and 2.0, 2 ꢁ CH; Ph),
7.11–7.07 (2H, m, 2 ꢁ CH; Ph), 7.01–6.86 (8H, m, 8 ꢁ CH; Ph),
6.65 (2H, br d, J 7.7, 2 ꢁ CH; Ph), 6.25 (1H, s, CHN), 4.98 (1H, q, J
oil; Rf [light petroleum ether (bp 40–60 °C)/diethyl ether (1:9)]
0.5; ½a 2D0
ꢃ
¼ þ71:7 (c 1.0, CHCl3), {lit.18
½
a 2D2
ꢃ
¼ þ71:2 (c 0.66,
CHCl3)}; mmax (CHCl3) cmꢀ1 1706 (C@O); dH (400 MHz; CDCl3)
7.45–6.98 (5H, m, 5 ꢁ CH; Ph), 3.75 (1H, q, J 7.2, PhCHCH3) and
1.5 (3H, d, J 7.2, PhCHCH3); dC (100 MHz; CDCl3) 180.4 (C@O),

E. Coulbeck, J. Eames / Tetrahedron: Asymmetry 19 (2008) 2223–2233
2233
139.7 (i-C; Ph), 128.72, 127.62 and 127.41 (5 ꢁ CH; Ph), 45.3
(PhCHCH3) and 18.1 (PhCHCH3) (Found MH+, 151.0753.
C9H11NO2þ) requires MH+, 151.0759).
Am. Chem. Soc. 1997, 119, 2584–2585; (d) Vedejs, E.; Daugulis, O. J. Am. Chem.
Soc. 2003, 125, 4166–4173.
5. (a) Coumbarides, G. S.; Dingjan, M.; Eames, J.; Flinn, A.; Motevalli, M.; Northen,
J.; Yohannes, Y. Synlett 2006, 101–105; (b) Coumbarides, G. S.; Eames, J.; Flinn,
A.; Northen, J.; Yohannes, Y. Tetrahedron Lett. 2005, 46, 849–853; (c) Boyd, E.;
Chavda, S.; Eames, J.; Yohannes, Y. Tetrahedron: Asymmetry 2007, 18, 476–482;
(d) Coumbarides, G. S.; Dingjan, M.; Eames, J.; Flinn, A.; Northen, J. Chirality
2007, 19, 321–328; (e) Coulbeck, E.; Eames, J. Tetrahedron: Asymmetry 2007, 18,
2313–2325; (f) Coulbeck, E.; Eames, J. Synlett 2008, 333–338.
4.21. Synthesis of 2-phenylpropionic acid (R)-28: hydrolysis of
oxazolidin-2-one (R,S)-syn-7
6. Coumbarides, G. S.; Dingjan, M.; Eames, J.; Flinn, A.; Northen, J.; Yohannes, Y.
Tetrahedron Lett. 2005, 46, 2897–2902. For a related kinetic resolution of
profens see patent WO/1996/002521 (dated 1-2-1996).
7. Bull, S. D.; Davies, S. G.; Garner, A. C.; Kruchinin, D.; Key, M. S.; Roberts, P. M.;
Savory, A. D.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2006, 4, 2945–
2964.
8. (a) Hintermann, T.; Seebach, D. Helv. Chem. Acta 1998, 81, 2093–2126; (b) Gaul,
C.; Schweizer, B. W.; Seiler, P.; Seebach, D. Helv. Chem. Acta 2002, 85, 1546–
1566.
9. (a) Evans, D. A.; Chapman, K. T.; Bisaha, J. Tetrahedron Lett. 1984, 25, 4071–
4074; (b) Evans, D. A. Aldrichim. Acta 1982, 15, 23–32.
In the same way as 2-phenylpropionic acid (S)-28, lithium
hydroxide monohydrate (13 mg, 0.30 mmol), hydrogen peroxide
(10 mg, 80 lL, 0.30 mmol, 40%/w) and oxazolidin-2-one syn-(R,S)-
7 (67 mg, 0.15 mmol) in THF/water (3:1; 4 mL), gave after an acidic
extraction, (ꢀ)-2-phenylpropionic acid (R)-28 (13 mg, 58%) as col-
ourless oil; >95% ee;17
½
a 2D0
ꢃ
¼ ꢀ71:8 (c 2.0, CHCl3) {lit.18
½
a 2D2
ꢃ
¼ ꢀ71:2 (c 0.66, CHCl3)}, which was spectroscopically identi-
cal to that reported previously; and the 4,5,5-triphenyloxazolidin-
2-one (S)-6 (44 mg, 95%) as a white solid; ½a D20
¼ ꢀ210:0 (c 0.4,
ꢃ
10. For our preliminary study into the use of 4,5,5-triphenyloxazolidin-2-one 6;
see: Chavda, S.; Coulbeck, E.; Dingjan, M.; Eames, J.; Flinn, A.; Northen, J.
Tetrahedron: Asymmetry 2008, 19, 1536–1548.
EtOH) {lit.18
ically identical to those previously obtained.
½
a 2D0
ꢃ
¼ ꢀ213:3 (c 0.5, EtOH)}; which was spectroscop-
11. Measured by 1H NMR (400 MHz) spectroscopy; for (rac)-anti-7, the hydrogen
singlet appears at 6.00 ppm (1H, s, PhCHN), whereas for (rac)-syn-7, the
hydrogen singlet appears at 6.02 ppm (1H, s, PhCHN).
Acknowledgements
12. Boyd, E.; Chavda, S.; Coulbeck, E.; Coumbarides, G. S.; Dingjan, M.; Eames, J.;
Flinn, A.; Krishnamurthy, A. K.; Namutebi, M.; Northen, J.; Yohannes, Y.
Tetrahedron: Asymmetry 2006, 17, 3406–3422 and references cited therein.
13. The less sterically demanding Evans oxazolidin-2-one 1 gave higher levels of
mutual recognition than using Seebach’s oxazolidin-2-one 6. For studies
involving oxazolidin-2-one 1, see Refs. 5, 6 and 12. For an additional study into
the use of Seebach’s oxazolidin-2-one 6 see: Chavda, S.; Coulbeck, E.; Dingjan,
M.; Eames, J.; Motevalli, M. Tetrahedron: Asymmetry 2008, 19, 1274–1284.
14. Interestingly, the characteristic CHN peak for the oxazolidin-2-ones (S,R)-syn-4
and (R,S)-syn-7 appears at 5.45 ppm and 6.25 ppm (by 1H NMR spectroscopy)
and 57.9 ppm and 66.0 ppm (by 13C NMR spectroscopy), respectively.
We are grateful to the EPSRC for a studentship (to E.C.) and The
University of Hull for their financial support (to J.E.), and the EPSRC
National Mass Spectrometry Service (Swansea) for accurate mass
determinations. We would like to thank Marco Dingjan for per-
forming some preliminary experiments and Onyx Scientific Lim-
ited (Drs. Tony Flinn and Julian Northen) for their interest in this
project.
15.
DRf [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] = 0.12.
16. The (S)-enantiomer of active ester 3 was recovered with 72% ee {½a D20
¼ þ47:2
ꢃ
(c 7.6, CHCl3); {lit.16 (S)-3;
½
a 2D0
ꢃ
¼ þ74:5 (c 4.9, CHCl3); lit.19 (R)-3;
References
½ ꢃ ¼ ꢀ75:0 (c 3.3, CHCl3)}. This was determined by derivatisation of the
a 2D0
parent carboxylic acid [(formed by LiOHꢄH2O-mediated hydrolysis of (S)-3]
1. For
a comprehensive review see: Fogassy, E.; Nogradi, M.; Palovics, E.;
using the method outlined in Ref. 17.
Schindler, J. Synthesis 2005, 1555–1568 and references cited therein.
2. For a comprehensive review into quasi-enantiomers, see: Zhang, Q.; Curran, D.
P. Chem. Eur. J. 2005, 11, 4866–4880.
3. For reviews see: (a) Eames, J. Angew. Chem., Int. Ed. 2000, 39, 885–888; (b)
Eames, J. In Organic Synthesis Highlights; VCH-Wiley, 2003; Vol. v, Chapter 17,
pp 151–164; (c) Dehli, J. R.; Gotor, V. Chem. Soc. Rev 2002, 31, 365–370; (d)
Dehli, J. R.; Gotor, V. ARKIVOC 2002, v, 196–202.
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M. J. Am. Chem. Soc. 2004, 126, 4490–4491; (b) Davies, S. G.; Garner, A. C.; Long,
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