Parallel kinetic resolution of active esters using designer oxazolidin-2-ones derived from phenylglycine

Article abstract of DOI:10.1016/j.tetasy.2008.06.020

The parallel kinetic resolution of racemic pentafluorophenyl 2-phenylpropionate using an equimolar combination of quasi-enantiomeric oxazolidin-2-ones is discussed. The levels of diastereoselectivity were excellent (>90% de) leading to separable quasi-enantiomeric oxazolidin-2-one adducts in good yield. This methodology was subsequently used to resolve a series of 2-aryl propionic and butanoic acids.

Full text of DOI:10.1016/j.tetasy.2008.06.020

Tetrahedron: Asymmetry 19 (2008) 1536–1548
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Parallel kinetic resolution of active esters using designer oxazolidin-2-ones
derived from phenylglycine
b
b
Sameer Chavda a, Elliot Coulbeck a, Marco Dingjan a, Jason Eames a, , Anthony Flinn , Julian Northen
*
a Department of Chemistry, University of Hull, Cottingham Road, Kingston upon Hull HU6 7RX, UK
b Onyx Scientific Limited, Units 97-98, Silverbriar, Sunderland Enterprise Park East, Sunderland SR5 2TQ, 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 racemic pentafluorophenyl 2-phenylpropionate using an equimolar
combination of quasi-enantiomeric oxazolidin-2-ones is discussed. The levels of diastereoselectivity were
excellent (>90% de) leading to separable quasi-enantiomeric oxazolidin-2-one adducts in good yield. This
methodology was subsequently used to resolve a series of 2-aryl propionic and butanoic acids.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 10 April 2008
Accepted 16 June 2008
Available online 14 July 2008
1. Introduction
oxazolidin-2-ones for the parallel kinetic resolution of pentafluoro-
phenyl 2-phenylpropionate rac-8 (Scheme 3). For this study, the
Over the last decade, there has been a steady increase in the
number of reports regarding the use of parallel kinetic resolutions
as a strategy for the separation of enantiomers.1,2 In particular,
Fox3 has elegantly demonstrated the resolution of racemic mixed
anhydrides (e.g., rac-3) using of a pair of quasi-enantiomeric Evans’
oxazolidin-2-ones (S)-1 and (R)-2 to give the corresponding oxaz-
olidin-2-one adducts 4 and 5 with near perfect levels of stereocon-
trol (Scheme 1). These adducts were efficiently separated3 using
Vedejs’ post-modification strategy4—by treatment of a near equi-
molar mixture of 4 and 5 with TBAF to give the more separable ad-
ducts 4 and 6 (Scheme 1).
synthesis and application of the majority of these designer oxazo-
lidin-2-ones have been reported.3,7–9
O
O
1. n-BuLi,
THF, -98 oC
HN
O
HN
O
2.
O
O
Ph
O
Ph
(2 equiv.)
(rac)-3
TBDMSO
Using a related approach, we have recently reported5 the com-
plementary parallel kinetic resolution of pentafluorophenyl 2-
phenylpropionate rac-8 using a pair of quasi-enantiomeric Evans’
oxazolidin-2-ones (R)-1 and (S)-7 to give the oxazolidin-2-one ad-
ducts (S,R)-syn-9 (in 60% yield) and (R,S)-syn-10 (in 60% yield) with
>90% and 76% diastereoisomeric excesses, respectively (Scheme 2).
From this preliminary study, it was evident that a better surrogate
oxazolidin-2-one [(S)-7] for the (S)-enantiomer of oxazolidin-2-
one 1 was needed to allow more efficient complementary stereo-
control (Scheme 2).5
(S)-1
(R)-2
O
O
O
O
Ph
Ph
Ph
N
O
N
O
Ph
TBDMSO
4
5
; 99% d.e.; 91%
O
O
O
O
Ph
Ph
Ph
Ph
2. Results and discussion
N
O
N
O
TBAF
We now report an extension of our study5,6 using a combination
of designer oxazolidin-2-ones (S)-2, (S)-11, (S)-12, (S)-13 and (S)-
14 (based on the parent phenylglycine derived oxazolidin-2-one
1) and discuss their use as complementary quasi-enantiomeric
HO
4; 99% d.e.; 91%
6; 98% d.e.; 87%
* Corresponding author. Tel.: +44 1482 466401; fax: +44 1482 466410.
E-mail address: j.eames@hull.ac.uk (J. Eames).
Scheme 1. Parallel kinetic resolution of anhydride (rac)-3 using quasi-enantiomeric
oxazolidin-2-ones (S)-1 and (R)-2.
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.06.020

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
1537
O
O
O
O
O
O
1. n-BuLi,
THF, -78 oC
Ph
Me
Ph
N
O
HN
Ph
O
HN
O
N
O
O
2.
Ph
H
H
Me
i-Pr
i-Pr
Ph
(S,R)-syn-9
OC6F5
Me
rac-8
(R)-1
10
syn-: anti-: 88:12; 60%
(R,S)-syn-
(S)-7
syn-: anti-: >95:5; 60%
Scheme 2. Parallel kinetic resolution of active ester (rac)-8 using quasi-enantiomeric oxazolidin-2-ones (R)-1 and (S)-7.
O
O
O
O
HN
O
HN
O
O
NH
O
NH
(R)-1
(S)-1
(R)-1
(S)-7
Quasi-enantiomeric relationship
Enantiomeric relationship
O
S
O
O
O
O
NH
O
NH
O
NH
O
NH
O
NH
OH
(S)-13
OTBDMS
(S)-2
(S)-11
(S)-12
14
(S)-
Scheme 3. Potential quasi-enantiomeric oxazolidin-2-one surrogates for (S)-1.
In an attempt to probe the complementarity of these designer
oxazolidin-2-ones, we first screened their mutual kinetic resolu-
tion of pentafluorophenyl 2-phenylpropionate rac-8 (Scheme 4).
Deprotonation of the oxazolidin-2-ones rac-1, rac-11, rac-12, rac-
13, rac-2 and rac-14 in THF at ꢀ78 °C, followed by the addition
of pentafluorophenyl 2-phenylpropionate rac-8, gave after 2 h at
ꢀ78 °C,10 the corresponding adducts rac-syn-9, rac-syn-15, rac-
syn-16, rac-syn-17, rac-syn-18 and rac-syn-19, respectively in good
yield with excellent levels of diastereoisomeric control (Scheme 4).
These oxazolidin-2-ones appeared to behave similarly to the
parent oxazolidin-2-one rac-1 with the exception of Seebach’s
oxazolidin-2-one rac-14 (Scheme 4: Entry 6). This particular
oxazolidin-2-one was less diastereoselective favouring the
formation of syn-adduct 19 in 53% yield with 78% de which was
presumably due to its larger sterically demanding nature7,11 and
associated effects (Scheme 4). By comparison, the phenolic
oxazolidin-2-one (S)-13 appeared to be less nucleophilic, requiring
a longer reaction time (12 h) for completion.
We first investigated the parallel kinetic resolution of penta-
fluorophenyl 2-phenyl propionate rac-8 using a quasi-enantiomeric
combination of oxazolidin-2-thione (R)-11 and oxazolidin-2-one
(S)-1 (Scheme 5). Deprotonation of an equimolar combination of
(R)-11 and (S)-1 with n-BuLi in THF at ꢀ78 °C, followed by the
addition of active ester rac-8, gave a separable mixture of the cor-
responding adducts (S,R)-syn-15 (in 55% yield) and (R,S)-syn-9 (in
59% yield) with 96% and 92% diastereoisomeric excesses, respec-
tively (Scheme 5). These adducts were easily separable by column
chromatography due to their difference in polarity (C@S bond ver-
parallel kinetic resolutions proceeded efficiently to give the ad-
ducts (S,R)-syn-9 and (R,S)-syn-19 (in 53% and 50% yields with
>96% and 96% des, respectively), (S,R)-syn-18 and (R,S)-syn-19
(in 81% and 73% yields with >96% and 90% des, respectively),
(S,R)-syn-17 and (R,S)-syn-19 (in 46% and 58% yields with >94%
and 84% des, respectively), (S,R)-syn-9 and (R,S)-syn-18 (in 68%
and 68% yields with >96% and 96% des, respectively), (S,R)-syn-
17 and (R,S)-syn-9 (in 56% and 82% yields with 90% and 86%
des, respectively), and (S,R)-syn-18 and (R,S)-syn-17 (in 61% and
49% yields with 96% and 96% des, respectively) (Scheme 6). The
majority of these parallel kinetic resolutions proceeded efficiently
leading to the complementary oxazolidin-2-one adducts with
excellent levels of diastereocontrol.12 The best combination of
oxazolidin-2-ones was found to be (R)-1 and (S)-2 as they ap-
peared to react at a near-equal and opposite rate, leading to opti-
mum enantiomeric separation.13 By comparison, the more
sterically demanding oxazolidin-2-one 14 appeared to react
slightly slower with pentafluorophenyl 2-phenylpropionate 8 than
oxazolidin-2-ones 1 and 2.
Whereas, phenolic oxazolidin-2-one 13 appeared to be less
nucleophilic than the structurally related oxazolidin-2-ones 1, 2
and 14 and required a significantly longer reaction time at an ele-
vated temperature (12 h at rt) for completion.13 These processes ap-
pear to proceed via a sequential kinetic resolution; the faster
reacting enantiomer (e.g., 1, 2 and 14) gave lower levels of diaste-
reocontrol (related to their mutual kinetic resolution) and the
slower reacting enantiomer 13 gave improved diastereoselection.14
In an attempt to improve chromatographic separation, we chose
to perform an in situ de-silylation of oxazolidin-2-one adduct (R,S)-
syn-18 [in the presence of (S,R)-syn-9 (formed in Scheme 6)] using
TBAF in THF (Scheme 7). Treatment of this crude mixture [derived
the parallel kinetic resolution of rac-8 using oxazolidin-2-ones (R)-
1 and (S)-2] with TBAF in THF for 3 h at rt, gave a separable mixture
of oxazolidin-2-ones (S,R)-syn-9 and (R,S)-syn-17 in 58% and 53%
yields (Scheme 7).
sus C@O bond) {DRF [light petroleum ether (bp 40–60 °C): diethyl
ether (1:1)] = 0.22}.
With this information in hand, we next probed the parallel ki-
netic resolution of pentafluorophenyl 2-phenylpropionate rac-8
using six pairs of quasi-enantiomeric oxazolidin-2-one combina-
tions (R)-1 and (S)-14, (R)-2 and (S)-14, (R)-13 and (S)-14, (R)-1
and (S)-2, (R)-13 and (S)-1, and (R)-2 and (S)-13 (Scheme 6). These

1538
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
O
O
O
O
O
1. n-BuLi (1.1 equiv.),
THF, -78 oC, 2 h
Ph
Ph
Me
+
HN
R
O
N
O
N
O
O
2.
H
Me
H
Ph
OC6F5
R
R
rac-
Me
rac-8
(1.1 equiv.)
syn-
anti-
(1 equiv.)
D.e.
Yield
Product
Oxazolidin-2-one
Entry
O
rac-syn-9:rac-anti-9
1
>94%5
70%5
HN
HN
O
>97: <3
rac-1
S
rac-syn-15:rac-anti-15
2
96%
55%
O
98: 2
rac-11
O
rac-syn-16:rac-anti-16
3
4
94%
92%
63%
50%
HN
HN
O
97: 3
12
rac-
O
rac-syn-17:rac-anti-17
O
96: 4
rac-13a,b
HO
O
rac-syn-18:rac-anti-18
5
>94%
78%
67%
53%
HN
HN
O
>97: <3
2
rac-
TBDMSO
6
O
19
19
rac-syn- :rac-anti-
O
89: 11
rac-14
a2.2 equiv. of n-BuLi used; b -78 ºC RT, 12 h.
Scheme 4. Mutual kinetic resolution of active ester (rac)-8 using oxazolidin-2-ones (rac)-1, (rac)-2, (rac)-11, (rac)-12, (rac)-13 and (rac)-14.
S
O
S
O
1. n-BuLi (2.2 equiv.)
O
O
THF, -78 o
C
Ph
Me
Ph
N
O
HN
Ph
O
HN
Ph
O
N
O
2.
O
H
H
Me
Ph
Ph
Ph
OC6F5
Me
rac-8
(2.2 equiv.)
(S,R)-syn-15
(R,S)-syn-9
syn-: anti-: 96:4; 59%
11
1
(R)-
(S)-
syn- :anti-: 98:2; 55%
(1 equiv.)
(1 equiv.)
Scheme 5. Parallel kinetic resolution of active ester (rac)-8 using a quasi-enantiomeric oxazolidin-2-ones (R)-11 and (S)-1.
Under our standard reaction conditions, it appears that the best
resolution processes appear to have some sequential resolution
character with improved diastereoselection (Scheme 6).
combination was the Fox’s and Evans’ oxazolidin-2-ones (R)-1 and
(S)-2, respectively (Scheme 6). They appeared to behave as near-
perfect quasi-enantiomeric partners reacting with rac-1 in an equal
and opposite stereochemical sense with similar reaction rates.13 By
comparison, the related oxazolidin-2-ones (R)-13 and (S)-14 re-
acted at different rates (to Evans’ oxazolidin-2-one 1) and these
With this information in hand, we next investigated the parallel
kinetic resolution of a variety of pentafluorophenyl 2-aryl substi-
tuted carboxylic acids15 rac-20, rac-21, rac-22 and rac-23 using a
combination of Evans’ and Fox’s oxazolidin-2-ones (R)-1 and (S)-
2 (Scheme 8). Treatment of an equimolar combination of oxazoli-

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
1539
O
O
O
O
O
O
1. n-BuLi (2.2 equiv.)
THF, -78 oC, 2 h
Ph
Ph
Me
HN
O
HN
Ph
O
N
O
N
O
2.
O
H
Me
H
Ph
Ph
Ph
Ph
Ph
Ph
OC6F5
Me
(rac)-8
(2.2 equiv.)
1
(R)-
(S)-14
9
(S,R)-syn-
(R,S)-syn-19
(1 equiv.)
(1 equiv.)
syn-:anti-: >98:<2; 53%
syn-:anti-: 98:2; 50%
O
O
O
O
O
O
1. n-BuLi (2.2 equiv.)
THF, -78 oC, 2 h
Ph
Ph
Me
HN
O
HN
Ph
O
N
O
N
O
O
2.
H
Me
H
Ph
Ph
Ph
Ph
Ph
Ph
OC6F5
Me
rac-8
(2.2 equiv.)
TBDMSO
TBDMSO
2
(R)-
(S)-14
19
(R,S)-syn-
(S,R)-syn-18
(1 equiv.)
(1 equiv.)
syn-:anti-: >98:<2; 81%
syn-:anti-: 95:5; 73%
O
O
O
O
O
O
1. n-BuLi (3.3 equiv.)
THF, -78 o
C RT, 12h
Ph
Ph
Me
HN
Ph
O
N
O
N
O
HN
O
2.
H
Me
H
O
Ph
Ph
Ph
Ph
Ph
Ph
OC6F5
Me
8
rac-
HO
(S,R)-syn-17
syn-:anti-: >97:<3; 46%
HO
(2.2 equiv.)
19
(R,S)-syn-
(S)-14
(R)-13
syn-:anti-: 92:8; 58%
(1 equiv.)
(1 equiv.)
O
O
O
O
O
O
1. n-BuLi (2.2 equiv.)
THF, -78 oC, 2 h
Ph
Ph
Me
HN
O
HN
O
N
O
N
O
O
2.
H
Me
H
Ph
OC6F5
Me
rac-8
(2.2 equiv.)
TBDMSO
TBDMSO
(S)-2
1
(R)-
(R,S)-syn-18
9
(S,R)-syn-
(1 equiv.)
(1 equiv.)
syn-:anti-: 98:2; 68%
syn-:anti-: >98:<2; 68%
O
O
O
O
O
O
1. n-BuLi (3.3 equiv.)
THF, -78 o
C
RT, 12h
Ph
Ph
Me
HN
O
HN
O
N
O
N
O
O
2.
H
Me
H
Ph
OC6F5
Me
rac-8
HO
(2.2 equiv.)
HO
(S)-1
(R)-13
17
(S,R)-syn-
(R,S)-syn-9
(1 equiv.)
(1 equiv.)
syn-:anti-: 95:5; 56%
syn-:anti-: 93:7; 82%
O
O
O
O
O
O
1. n-BuLi (3.3 equiv.)
THF, -78 o
C RT, 12h
Ph
Ph
Me
HN
O
HN
O
N
O
N
O
O
2.
H
Me
H
Ph
OC6F5
Me
rac-8
(2.2 equiv.)
TBDMSO
HO
TBDMSO
(S,R)-syn-
HO
(R)-2
13
(S)-
18
syn-:anti-: 98:2; 61%
(R,S)-syn-17
syn-:anti-: 98:2; 49%
(1 equiv.)
(1 equiv.)
Scheme 6. Parallel kinetic resolution of active ester (rac)-8 using quasi-enantiomeric oxazolidin-2-ones 1, 2, 13 and 14.
din-2-ones (R)-1 and (S)-2 with n-BuLi in THF at ꢀ78 °C, followed
by the addition of active esters rac-20, rac-21, rac-22 and rac-23,
gave the corresponding oxazolidin-2-one adducts (S,R)-syn-24
and (R,S)-syn-28 (in 71% and 62% yields with >96% and >96% des,
respectively), (S,R)-syn-25 and (R,S)-syn-29 (in 69% and 72% yields
with 94% and 94% des, respectively), (S,R)-syn-26 and (R,S)-syn-30
(in 50% and 53% yields with 94% and 94% des, respectively) and
(S,R)-syn-27 and (R,S)-syn-31 (in 70% and 72% yields with >96%
and >96% des, respectively) (Scheme 8). These reactions proceeded
efficiently leading to the required separable oxazolidin-2-one ad-
ducts in good yield (ꢁ60% yield) with high diastereoselectivity
(ꢁ94% de) (Scheme 8).
Hydrolysis of
a pair of quasi-enantiomeric adducts [e.g.,
(S,R)-syn-9 and (R,S)-syn-17] using LiOH monohydrate/hydrogen

1540
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
O
O
O
O
O
O
O
O
Ph
Ph
Me
Ph
Ph
Me
N
O
N
O
N
O
N
O
TBAF
H
Me
H
H
Me
H
THF, H2O
HO
(R,S)-syn-17
TBDMSO
(R,S)-syn-18
(S,R)-syn-9
syn-:anti-: >98:<2
(S,R)-syn-9
syn-:anti-: >98:<2; 58%
syn-:anti-: 98:2
syn-:anti-: 98:2; 53%
Scheme 7. Post-modification of oxazolidin-2-one adduct (R,S)- syn-18 to give (R,S)-syn-17.
O
O
O
O
O
O
1. n-BuLi (2.2 equiv.)
THF, -78 oC
Ar
Ar
HN
O
HN
O
N
O
N
O
H
R
R H
2.
O
Ar
OC6F5
R
rac-
TBDMSO
TBDMSO
(R,S)-syn-
(2.2 equiv.)
(S)-2
(1 equiv.)
(S,R)-syn-
(R)-1
(1 equiv.)
Oxazolidin-2-oneadducts
Oxazolidin-2-one adducts
Active ester
R
D.e.
D.e.
Yield
68%
Ar
Yield
68%
derived from (R)-1
derived from (S)-2
rac-8
Ph
(S,R)-syn-9: (R,R)-anti-9
(R,S)-syn-18: (S,S)-anti-18
Me
96%
96%
96%
96%
>98:<2
98:2
24
28
>98:<2
28
29
(S,R)-syn- : (R,R)-anti-24
(R,S)-syn- : (S,S)-anti-
rac-20
rac-21
Ph
Et
62%
72%
71%
69%
>98:<2
25
29
(S,R)-syn- : (R,R)-anti-25
(R,S)-syn- : (S,S)-anti-
4-MeC6H4-
Me
94%
94%
96%
94%
94%
96%
97:3
(S,R)-syn-26: (R,R)-anti-26
97:3
97:3
(R,S)-syn-30: (S,S)-anti-30
53%
72%
rac-22
4-ClC6H4-
Me
Me
50%
70%
97:3
27
31
31
(S,R)-syn- : (R,R)-anti-27
(R,S)-syn- : (S,S)-anti-
rac-23
4-i-BuC6H4-
>98:<2
>98:<2
Scheme 8. Parallel kinetic resolution of active esters 8 and 20-23 using oxazolidin-2-ones (R)-1 and (S)-2.
peroxide proceeded efficiently, leading to the enantiomerically
pure 2-phenylpropionic acids (S)- and (R)-32 in 92% and 90% yield
(Scheme 9). In addition, hydrolysis of the remaining complemen-
tary designer oxazolidin-2-ones (R,S)-syn-18 and (R,S)-syn-19 gave
the required enantiomerically pure 2-phenylpropionic acid (R)-32
in 90% and 58% yields, respectively (Scheme 9).16
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 inter-
nal deuterium lock. Chemical shifts are quoted in parts per mil-
lion 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 Activ-
ity Ltd polarimeter. The active esters, pentafluorophenyl 2-phen-
ylpropionate rac-8, pentafluorophenyl phenylbutanoate rac-20,
pentafluorophenyl 2-(4-methylphenyl)propionate rac-21, penta-
fluorophenyl 2-(4-chlorophenyl)propionate rac-22 and pentaflu-
orophenyl 2-(4-isobutylphenyl)propionate rac-23 have been
reported elsewhere.15
3. Conclusion
In conclusion, we have reported the efficient parallel kinetic
resolution of pentafluorophenyl 2-phenylpropionate rac-8 using
combinations of oxazolidin-2-ones 1, 2, 13 and 14. The levels of
diastereocontrol were found to be excellent, favouring the forma-
tion of the corresponding syn-oxazolidin-2-one adducts 9, 18, 17
and 19 in good yields with excellent levels of diastereoselectivity.
The preferred combination of quasi-enantiomeric oxazolidin-2-
ones for the parallel kinetic resolution of pentafluorophenyl
2-phenylpropionate rac-8 was found to be the oxazolidin-2-ones
(R)-1 and (S)-2. These oxazolidin-2-ones were shown to be efficient
quasi-enantiomers for the parallel kinetic resolution and separa-
tion of a variety of 2-aryl propionic and butanoic acids.
4.2. 4-Phenyl-oxazolidin-2-thione rac-118,9
Carbon disulfide (1.74 g, 22.92 mmol) was added to a stirred
solution of rac-phenylglycinol (1.50 g, 10.94 mmol) and aqueous
NaHCO3 (20 mL, 1 M) at room temperature. The resulting solu-
tion was stirred at 100 °C for 15 min. After being cooled to
room temperature, the reaction mixture was extracted with
dichloromethane (3 ꢂ 50 mL). The combined organic layers were
dried over MgSO4 and evaporated under reduced pressure to
give the oxazolidin-2-thione rac-11 (1.35 g, 69%) as a white
powder; RF [diethyl ether] 0.78; mp 158–162 °C; mmax (CHCl3)
4. Experimental
4.1. General
All solvents were distilled before use. All reactions were car-
ried out under nitrogen using oven-dried glassware. Flash column

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
1541
O
4.4. 4-(2,5-Dihydrophenyl)-oxazolidin-2-one rac-12
O
O
Ph
Ph
LiOH, H2O2
OH
N
O
Anhydrous potassium carbonate (0.31 g, 2.23 mmol) was added
to a solution of rac-2,5-dihydrophenylglycinol (3.10 g, 22.3 mmol)
and diethylcarbonate (5.55 g, 5.69 mL, 46.99 mmol). The resulting
mixture was subjected to short-path distillation for 4 h, at
135 °C, to give the by-product (ethanol), which was collected in
the receiver flask. The reaction was quenched with water and ex-
tracted with dichloromethane (2 ꢂ 50 mL). The combined organic
layers were dried over MgSO4 and evaporated under reduced pres-
sure to give the crude oxazolidin-2-one rac-12. This residue was
re-crystallised from a mixture of hot light petroleum ether (bp
40–60 °C):ethyl acetate: (1:2) to give 4-(2,5-dihydrophenyl)-oxaz-
olidin-2-one rac-12 (2.43 g, 66%) as a white solid;RF [diethyl ether]
0.44; mp 74–78 °C; mmax (CHCl3) cmꢀ1 1750 (C@O); dH (400 MHz;
CDCl3) 5.86 (1H, br s, NH), 5.75–5.60 (3H, br s, 3 ꢂ CH@), 4.47
(1H, t, J 8.6, CHAHBO), 4.33 (1H, dd, J 8.6 and 6.1, CHAHBO), 4.08
(1H, dd, J 8.6 and 6.1, CHN), 2.72–2.56 (4H, m, 2 ꢂ CH2); dC
(100 MHz; CDCl3) 159.8 (C@O), 132.3 (R2C@), 123.9, 123.1 and
122.9 (3 ꢂ CH@), 68.9 (CH2O), 57.8 (CHN), 26.3 and 23.9
(2 ꢂ CH2) (Found MH+, 166.0683; C9H12NO2 requires 166.0683).
THF/H2O (3:1)
H
Me
H
Me
(
S
)-32; 92%
(
S,
R)-syn-9
O
O
O
Ph
Me
LiOH, H2O2
Ph
OH
N
O
THF/H2O (3:1)
H
Me
H
(
R
)-32; 90%
HO
(
R
,S
)-syn-17
O
O
O
Ph
Me
LiOH, H2O2
Ph
OH
N
O
THF/H2O (3:1)
H
H
Me
(
R
)-32; 90%
4.5. 4-(4-tert-Butyldimethylsilyoxyphenyl)-oxazolidin-2-one
rac-2 and 4-(4-hydroxyphenyl)-oxazolidin-2-one rac-13
TBDMSO
(
R
,
S
)-syn-18
Using Fox’s protocol,3 thionyl chloride (10.4 g, 6.3 mL,
87.1 mmol) was added to the rac-N-tert-butoxycarbonyl-(4-tert-
butyldimethylsilyoxyphenyl)-glycinol (4.00 g, 10.9 mmol). The
resulting solution was stirred for 12 h. The remaining thionyl chlo-
ride was removed through distillation, and the residual thionyl
chloride was removed under reduced pressure. The resulting resi-
due was dissolved in ethyl acetate (20 mL) and sequentially
washed with water, NaHCO3 (saturated) and brine, dried over
MgSO4 and concentrated under reduced pressure. Dichlorometh-
ane (50 mL) was added, and the insoluble 4-(4-hydroxyphenyl)-
oxazolidin-2-one rac-13 (0.29 g, 15%) was removed through filtra-
tion; white powder; mp 141–143 °C; RF [diethyl ether] 0.05; RF
[EtOAc] 0.70; mmax (ethanol) cmꢀ1 2974 (NH) and 1751 (C@O); dH
(400 MHz; CDCl3) 9.47 (1H, s, OH), 8.03 (1H, s, NH), 7.12 (2H, dt,
J 8.5 and 2.4, 2 ꢂ CH; Ar), 6.75 (2H, dt, J 8.5 and 2.4, 2 ꢂ CH; Ar),
4.80 (1H, dd, J 8.4 and 6.8, CHN), 4.58 (1H, t, J 8.4, CHAHBO) and
3.93 (1H, dd, J 8.4 and 6.8, CHAHBO); dC (100 MHz; CDCl3) 158.9
O
O
O
Ph
Me
LiOH, H2O2
Ph
Me
OH
N
O
THF/H2O (3:1)
H
H
Ph
Ph
Ph
(R)-32; 58%
(R,S)-syn-19
Scheme 9. Synthesis of 2-phenylpropionic acids (S)- and (R)-32.
cmꢀ1 1709 (C@S); dH (400 MHz; CDCl3) 8.17 (1H, s, NH), 7.42–
7.34 (3H, m, 3 ꢂ CH; Ph), 7.30–7.27 (2H, m, 2 ꢂ CH; Ph), 5.13
(1H, dd, J 8.9 and 6.9, CHAHBO), 4.95 (1H, t, J 8.9, CHN) and
4.38 (1H, dd, J 8.9 and 6.9, CHAHBO); dC (100 MHz; CDCl3)
189.7 (NC@S), 137.7 (i-C; Ph), 129.32, 129.11 and 126.12
(5 ꢂ CH; Ar), 77.5 (CH2O) and 60.1 (CHN) (Found MH+,
180.0481; C9H10NOS requires 180.0478).
(C@O), 157.2 (i-CO; Ar), 131.0 (i-C; Ar), 127.42 and 115.42
þ
(4 ꢂ CH; Ar), 71.6 (CH2O) and 54.8 (CHN) (Found MNH4
,
4.3. 2,5-Dihydrophenylglycinol
197.0923; C9H13N2O3 requires 197.0921). The filtrate was concen-
trated under reduced pressure, and re-crystallised in hot ethyl
acetate to give the 4-[4-(tert-butyldimethylsilyloxy)phenyl]-oxaz-
olidin-2-one rac-2 (1.56 g, 49%) as a white crystalline solid; mp
Lithium aluminium hydride (1.85 g, 49.5 mmol) was slowly
added to THF (100 mL). The resulting solution was cooled to 0 °C
using an ice-bath. rac-2,5-Dihydrophenylglycine (5.02 g,
32.76 mmol) was then slowly added for over 5 min. The ice-bath
was then removed, and the resulting solution was refluxed for
16 h. The reaction mixture was then cooled to 10 °C, and diluted
with diethyl ether (50 mL). The reaction was sequentially
quenched with water (5 mL), sodium hydroxide (15%, 5 mL) and
water (15 mL). The resulting solution was stirred for 30 min and
the white precipitate was filtered. The filter cake was washed with
diethyl ether (3 ꢂ 150 mL) and the organic filtrates were dried over
MgSO4, and concentrated under reduced pressure to give rac-2,5-
110–112 °C; RF [diethyl ether] 0.42; RF [EtOAc] 0.80; mmax (ethanol)
cmꢀ1 2974 (NH) and 1750 (CO); dH (400 MHz; CDCl3) 8.13 (1H, s,
NH), 7.27 (2H, br d, J 8.4, 2 ꢂ CH; Ar), 6.91 (2H, br d, J 8.4,
2 ꢂ CH; Ar), 4.91 (1H, dd, 8.4 and 6.7, CHN), 4.67 (1H, t, J 8.4, CHAH-
BO), 4.01 (1H, dd, J 8.4 and 6.7, CHAHBO), 0.99 (9H, s, 3 ꢂ CH3C; t-
Bu) and 0.22 (6H, s, 2 ꢂ CH3Si); dC (100 MHz; CDCl3) 158.9
(C@O), 154.9 (i-CO; Ar), 133.8 (i-C; Ar), 127.52 and 120.12
(4 ꢂ CH; Ar), 71.5 (CH2O), 54.7 (CHN), 25.63 (3 ꢂ CH3C; t-Bu),
17.9 (CH3C; t-Bu) and ꢀ4.52 (2 ꢂ CH3Si) (Found MNa+, 316.1342;
C15H23NO3SiNa requires 316.1339).
dihydrophenylglycinol (3.32 g, 73%) as
a colourless oil; mmax
(CHCl3) cmꢀ1 3355 (NH), 3030 (NH) and 2881 (OH); dH
(400 MHz; CDCl3) 5.75–5.60 (3H, m, 3 ꢂ CH@), 3.63 (1H, dd, J
10.6 and 4.2, CHAHBO), 3.43 (1H, dd, J 10.6 and 7.2, CHAHBO),
3.31 (1H, dd, J 7.2 and 4.2, CHN), 2.70–2.50 (5H, m, 2 ꢂ CH2 and
OH) and 2.41 (2H, br s, NH2); dC (100 MHz; CDCl3) 135.2 (R2C@),
124.0, 123.7 and 120.0 (3 ꢂ CH@), 64.8 (CH2O), 58.1 (CHN), 26.3
and 26.1 (2 ꢂ CH2); m/z 140.1 (100%, MH+).
4.6. 4,5,5-Triphenyl-oxazolidin-2-one rac-14
Synthesised by mixing an equimolar amount of its (S)- and (R)-
14 enantiomers; characterisation data: RF [diethyl ether] 0.50; mp
219–220 °C; mmax (CHCl3) cmꢀ1 1763 (C@O); dH (400 MHz; CDCl3)
7.62 (2H, dt, J 7.2 and 2.2, 2 ꢂ CH; Ph), 7.39–7.26 (3H, m, 3 ꢂ CH;
Ph), 7.09–6.98 (5H, m, 5 ꢂ CH; Ph), 6.95 (5H, br s, 5 ꢂ CH; Ph),

1542
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
5.54 (1H, s, CHN) and 5.53 (1H, br s, NH); dC (100 MHz; CDCl3)
158.0 (C@O), 142.8, 138.8 and 137.1 (3 ꢂ i-C; 3 ꢂ Ph), 128.62,
s, 2 ꢂ CH3Si); dC (100 MHz; CDCl3) 158.9 (C@O), 154.9 (i-CO; Ar),
133.8 (i-C; Ar), 127.52 and 120.12 (4 ꢂ CH; Ar), 71.5 (CH2O), 54.7
(CHN), 25.63 (3 ꢂ CH3C; t-Bu), 17.9 (CH3C; t-Bu) and ꢀ4.52
(2 ꢂ CH3Si) (Found MNa+, 316.1342; C15H23NO3SiNa requires
316.1339); m/z 293 (10%, M+), 236 (ArCH@NH+) and 119 (100,
OC6H4CH@NH+).
128.51, 128.41, 128.32, 127.82, 127.52, 127.31, 126.52 and 126.22
þ
(15 ꢂ CH; 3 ꢂ Ph), 90.7 (CPh2O) and 65.8 (CHN) (Found MNH4
,
333.1598; C21H21N2O2 requires 333.1598).
4.7. 4-Phenyl-oxazolidin-2-thione (R)-118,9
4.10. 4-[4-(tert-Butyldimethylsilyloxy)phenyl]-oxazolidin-2-
one (R)-2 and 4-(4-hydroxyphenyl)-oxazolidin-2-one (R)-13
In the same way as for the oxazolidin-2-thione rac-11,8 (R)-phe-
nylglycinol (1.59 g, 11.5 mol) and carbon disulfide (1.90 g,
24.9 mmol) in aqueous NaHCO3 (20 mL, 1 M) gave the oxazoli-
din-2-thione (R)-11 (1.26 g, 65%) as a white powder; RF [diethyl
In the same way as for the oxazolidin-2-one rac-2, thionyl chlo-
ride (12.9 g, 7.9 mL, 0.108 mmol) and (R)-N-tert-butoxycarbonyl-
(4-tert-butyldimethylsilyoxyphenyl)-glycinol (5.00 g, 13.6 mmol)
gave the 4-(4-hydroxyphenyl)-oxazolidin-2-one (R)-13 (0.38 g,
16%) as a white powder; RF [diethyl ether] 0.42; mp 201–204 °C;
ether] 0.78; mp 120–121 °C (lit.9 120–121 °C); ½a D25
¼ ꢀ80:3 (c
ꢃ
0.3, CHCl3), lit.8
½
a 2D5
ꢃ
¼ ꢀ79:3 (c 0.21, CHCl3); lit.9 for (S)-11
½
a 2D5
ꢃ
¼ þ82:7 (c 0.21, CHCl3); mmax (CHCl3) cmꢀ1 1709 (C@S); dH
(400 MHz; CDCl3) 8.17 (1H, s, NH), 7.42–7.34 (3H, m, 3 ꢂ CH;
Ph), 7.30–7.27 (2H, m, 2 ꢂ CH; Ph), 5.13 (1H, dd, J 8.9 and 6.9,
CHAHBO), 4.95 (1H, t, J 8.9, CHN) and 4.38 (1H, dd, J 8.9 and 6.9,
CHAHBO); dC (100 MHz; CDCl3) 189.7 (NC@S), 137.7 (i-C; Ph),
129.32, 129.11 and 126.12 (5 ꢂ CH; Ar), 77.5 (CH2O) and 60.1
(CHN) (Found MH+, 180.0478; C9H9NOS requires 180.0481).
½
a 2D0
ꢃ
¼ ꢀ39:4 (c 0.7, EtOH) (Found MNH4þ, 197.0919; C9H13N2O3
requires 197.0921) (Found M+, 179.0574; C9H9NO3 requires
179.0577). This compound was spectroscopically identical to its
above (S)-enantiomer; and 4-[4-(tert-butyldimethylsilyloxy)-
phenyl]-oxazolidin-2-one (R)-2 (1.79 g, 45%) as a white crystalline
solid; RF [diethyl ether] 0.71; mp 130–132 °C; ½a D20
ꢃ
¼ ꢀ34:8 (c 1.7,
ethanol); ½a 2D0
ꢃ
¼ ꢀ37:2 (c 1.28, DMSO) {lit.3
½
a 2D0
ꢃ
¼ ꢀ37:6 (c 1.05,
4.8. 4-Phenyl-oxazolidin-2-one (S)-1
THF)} (Found M+, 293.1445; C15H23NO3Si requires 293.1442); m/z
293 (10%, M+), 236 (ArCH@NH+) and 119 (100, OC6H4CH@NH+).
This compound was spectroscopically identical to its above (S)-
enantiomer.
In the same way as for the oxazolidin-2-one rac-12, (S)-phenyl-
glycinol (8.47 g, 61.8 mmol), potassium carbonate (0.85 g,
6.1 mmol) and diethylcarbonate (15.32 g, 15.71 mL, 129.8 mmol)
gave the (S)-oxazolidin-2-one 1 (5.70 g, 57%) as a white powder.
This was recrystallised from a mixture of hot light petroleum
ether (bp 40–60 °C)/ethyl acetate: (1:2) to give 4-phenyl-oxazoli-
din-2-one (S)-1 as white crystals; mp 130–133 °C, (lit.17 131–
4.11. 4,5,5-Triphenyl-oxazolidin-2-one (S)-14
Available from Aldrich Chemical Limited and Onyx Scientific
Limited; characterisation data: white powder; RF [diethyl ether]
133 °C); RF [ethyl acetate/ethanol (9:1)] 0.71; ½a D22
ꢃ
¼ þ47:8 (c
0.50; mp 232–234 °C; ½a D20
¼ ꢀ213:3 (c 0.5, EtOH); mmax (CHCl3)
ꢃ
0.8, CHCl3) {for (S)-; lit.17
½
a 2D0
ꢃ
¼ þ49:5 (c 2.1, CHCl3)}; mmax
cmꢀ1 1763 (C@O); dH (400 MHz; CDCl3) 7.62 (2H, dt, J 7.2 and
2.2, 2 ꢂ CH; Ph), 7.39–7.26 (3H, m, 3 ꢂ CH; Ph), 7.09–6.98 (5H,
m, 5 ꢂ CH; Ph), 6.95 (5H, br s, 5 ꢂ CH; Ph), 5.54 (1H, s, CHN) and
5.53 (1H, br s, NH); dC (100 MHz; CDCl3) 158.0 (C@O), 142.8,
138.8 and 137.1 (3 ꢂ i-C; 3 ꢂ Ph), 128.62, 128.51, 128.41, 128.32,
127.82, 127.52, 127.31, 126.52 and 126.22 (15 ꢂ CH; 3 ꢂ Ph), 90.7
(CPh2O) and 65.8 (CHN) (Found MNH4þ, 333.1598; C21H21N2O2 re-
quires 333.1598); m/z 315 (5%, M+), 256 (10, PhCHCPh2þ), 183 (100,
Ph2C@OH+), 105 (90, PhCH@NH+) and 77 (80, Ph+).
(CHCl3) cmꢀ1 3262 (NH) and 1736 (C@O); dH (400 MHz; CDCl3)
7.41–7.31 (5H, m, 5 ꢂ CH; Ph), 5.69 (1H, s, NH), 4.93 (1H, dd, J
8.6 and 6.9, CHN), 4.72 (1H, t, J 8.6, CHAHBO) and 4.17 (1H, dd, J
8.6 and 6.9, CHAHBO); dC (100 MHz; CDCl3) 159.4 (C@O), 139.3
(i-C; Ph), 129.2,2 128.91 and 126.02 (5 ꢂ CH; Ph), 72.5 (CH2O)
and 56.3 (CHN) (Found MNH4þ, 181.0970; C9H9NO2 requires
181.0972).
4.9. 4-[4-(tert-Butyldimethylsilyloxy)phenyl]-oxazolidin-2-one
(S)-2 and 4-(4-Hydroxyphenyl)-oxazolidin-2-one (S)-13
5. Mutual kinetic resolution of pentafluorophenyl 2-
phenylpropionate rac-8
In the same way as for the oxazolidin-2-one rac-2, thionyl chlo-
ride (12.9 g, 7.9 mL, 0.108 mmol) and (S)-N-tert-butoxycarbonyl-
(4-tert-butyldimethylsilyoxyphenyl)-glycinol (5.00 g, 13.6 mmol)
gave the 4-(4-hydroxyphenyl)-oxazolidin-2-one (S)-13 (0.34 g,
14%) as a white powder; mp 201–204 °C; RF [diethyl ether] 0.42;
5.1. (2RS,4SR)-3-(2-Phenylpropionyl)-4-phenyl-oxazolidin-2-
thione rac-syn-15
½
a 2D0
ꢃ
¼ þ41:4 (c 1.7, ethanol); mmax (ethanol) cmꢀ1 2974 (NH) and
n-BuLi (0.37 mL, 2.5 M in hexane, 0.92 mmol) was added to a
stirred solution of 4-phenyl-oxazolidin-2-thione rac-11 (0.15 g,
0.84 mmol) in THF at ꢀ78 °C. After stirring for 1 h, a solution of
pentafluorophenyl 2-phenylpropionate rac-8 (0.29 g, 0.92 mmol)
in THF (1 mL) was added. The resulting mixture was stirred for
2 h at ꢀ78 °C. The reaction was quenched with water (10 mL).
The organic layer was extracted with diethyl ether (2 ꢂ 10 mL),
dried (over MgSO4) and evaporated under reduced pressure to give
a mixture of diastereoisomeric oxazolidin-2-ones 15 [ratio 98:2:
syn-:anti-]. The crude residue was purified by flash chromatogra-
phy on silica gel eluting with light petroleum ether (bp 40–
60 °C)/diethyl ether (7:3) to give the oxazolidin-2-thione (RS,SR)-
syn-15 (0.143 g, 55%) as a white solid;RF [light petroleum ether
(bp 40–60 °C)/diethyl ether: (1:1)] 0.67; mp 118–119 °C; mmax
(CHCl3) cmꢀ1 1700 (C@S); dH (400 MHz; CDCl3) 7.20–7.08 (6H, m,
6 ꢂ CH; PhA and PhB), 6.94 (2H, dt, J 6.9 and 1.8, 2 ꢂ CH; PhA),
6.88 (2H, dt, J 7.0 and 1.8, 2 ꢂ CH; PhB), 5.98 (1H, q, J 6.9, PhCHCH3),
1751 (C@O); dH (400 MHz; CDCl3) 9.47 (1H, s, OH), 8.03 (1H, s,
NH), 7.12 (2H, dt, J 8.5 and 2.4, 2 ꢂ CH; Ar), 6.75 (2H, dt, J 8.5
and 2.4, 2 ꢂ CH; Ar), 4.80 (1H, dd, J 8.4 and 6.8, CHN), 4.58 (1H, t,
J 8.4, CHAHBO) and 3.93 (1H, dd, J 8.4 and 6.8, CHAHBO); dC
(100 MHz; CDCl3) 158.9 (C@O), 157.2 (i-CO; Ar), 131.0 (i-C; Ar),
127.42 and 115.42 (4 ꢂ CH; Ar), 71.6 (CH2O) and 54.8 (CHN) (Found
MNH4þ, 197.0923; C9H13N2O3 requires 197.0921); m/z 179 (20%,
M+), 149 (20, M+-CH2O), 120 (100, ArCH@CHþ2 ), 107 (25,
ArCHþ2 ) and 94 (15, PhOH+); and 4-[4-(tert-butyldimethyl-
silyloxy)phenyl]-oxazolidin-2-one (S)-2 (1.99 g, 50%) as a white
crystalline solid; mp 130–132 °C; RF [diethyl ether] 0.71;
½
a 2D0
ꢃ
¼ þ36:3 (c 2.0, ethanol); mmax (ethanol) cmꢀ1 2974 (NH) and
1750 (C@O); dH (400 MHz; CDCl3) 8.13 (1H, s, NH), 7.27 (2H, br
d, J 8.4, 2 ꢂ CH; Ar), 6.91 (2H, br d, J 8.4, 2 ꢂ CH; Ar), 4.91 (1H,
dd, J 8.4 and 6.7, CHN), 4.67 (1H, t, J 8.4, CHAHBO), 4.01 (1H, dd, J
8.4 and 6.7, CHAHBO), 0.99 (9H, s, 3 ꢂ CH3C; t-Bu) and 0.22 (6H,

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
1543
5.61 (1H, dd, J 9.2 and 6.1, CHN), 4.68 (1H, t, J 9.2, CHAHBO), 4.20
(1H, dd, J 9.2 and 6.1, CHAHBO) and 1.35 (3H, d, J 6.9, PhCHCH3),
dC (100 MHz; CDCl3) 185.2 (C@S), 174.8 (C@O), 139.1 and 136.9
(2 ꢂ i-C; 2 ꢂ Ph), 128.8,2 128.7,1 128.5,2 128.3,2 127.11 and 126.42
(10 ꢂ CH; 2 ꢂ Ph), 73.6 (CH2O), 62.6 (CHN), 43.9 (PhCHCH3) and
18.7 (PhCHCH3) (Found MH+, 312.1054; C18H17NO2S requires
312.1053).
(0.32 g, 1.10 mmol) and pentafluorophenyl 2-phenylpropionate
rac-8 (0.38 g, 1.21 mmol) gave a mixture of two diastereoisomeric
oxazolidin-2-ones 18 [ratio >97:3: 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 oxazolidin-2-one (RS,SR)-syn-18 (0.31 g, 67%) as a white crys-
talline solid; mp 120–121 °C; RF [light petroleum ether (bp 40–
60 °C)/diethyl ether (1:1)] 0.51; mmax (CHCl3) cmꢀ1 1774 (C@O)
and 1711 (C@O); dH (400 MHz; CDCl3) 7.41–7.17 (5H, m, 5 ꢂ CH;
Ph), 7.19 (2H, dt, J 8.6 and 2.4, 2 ꢂ CH; Ar), 6.84 (2H, dt, J 8.6 and
2.4, 2 ꢂ CH; Ar), 5.29 (1H, dd, J 8.6 and 3.1, CHN), 5.10 (1H, q, J
7.0, PhCHCH3), 4.52 (1H, t, J 8.6, CHAHBO), 4.22 (1H, dd, J 8.6 and
3.1, CHAHBO), 1.41 (3H, d, J 7.0, PhCHCH3), 0.98 (9H, s, 3 ꢂ CH3C;
t-Bu) and 0.20 (6H, s, 2 ꢂ CH3Si); dC (100 MHz; CDCl3) 174.5
(NC@O), 155.9 (i-C; Ar), 153.3 (OC@O), 140.2 (i-C; Ph), 131.9 (i-C;
Ar), 128.62, 128.22 and 127.21 (5 ꢂ CH; Ph), 127.32 and 120.62
(4 ꢂ CH; Ar), 69.9 (CH2O), 57.6 (CHN), 43.2 (PhCHCH3), 25.63
(3 ꢂ CH3C; t-Bu), 19.4 (PhCHCH3), 18.1 (CH3C; t-Bu) and -4.42
(2 ꢂ CH3Si); (Found MNa+, 448.1912; C24H31NO4SiNa requires
448.1915); m/z 425 (15%, M+), 132 (60, Ph(CH3)C@C@O+) and 105
(100, PhCHCHþ3 ).
5.2. (2RS,4SR)-3-(2-Phenylpropionyl)-4-(2,5-dihydrophenyl)-
oxazolidin-2-one rac-syn-16
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.40 mL, 2.5 M in hexane, 0.99 mmol), oxazolidin-2-one rac-12
(0.15 g, 0.90 mmol) and pentafluorophenyl 2-phenylpropionate
rac-8 (0.31 g, 0.99 mmol) gave a mixture of two diastereoisomeric
oxazolidin-2-ones 16 [ratio 97:3: (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 oxazolidin-2-one (RS,SR)-syn-16 (0.17 g, 63%) as a viscous col-
ourless oil; RF [light petroleum ether (bp 40–60 °C)/diethyl ether
(1:1)] 0.68; mmax (CHCl3) cmꢀ1 1775 (C@O) and 1705 (C@O); dH
(400 MHz; CDCl3) 7.41–7.17 (5H, m, 5 ꢂ CH; Ph), 5.60 (1H, m,
CH@), 5.50 (1H, m, CH@), 5.43 (1H, m, CH@), 5.10 (1H, q, J 7.0,
PhCHCH3), 4.89 (1H, dd, J 8.8 and 3.8, CHN), 4.39 (1H, t, J 8.8, CHAH-
BO), 3.96 (1H, dd, J 8.8 and 3.8, CHAHBO), 2.66–2.50 (2H, m, 2 ꢂ CH),
2.45–2.31 (1H, m, CH), 2.02–1.91 (1H, m, CH) and 1.43 (3H, d, J 7.0,
PhCHCH3); dC (100 MHz; CDCl3) 173.8 (NC@O), 153.1 (OC@O),
140.0 (i-C; Ph), 130.5 (R2C@), 128.5,2 128.12 and 127.01 (5 ꢂ CH;
Ph), 123.6, 122.9 and 122.8 (3 ꢂ CH@), 66.6 (CH2O), 58.7 (CHN),
43.4 (PhCHCH3), 26.1 and 23.6 (2 ꢂ CH2) and 18.6 (PhCHCH3)
(Found M+, 295.1201; C18H19NO3 requires 295.1201); (Found
MNH4þ, 315.1702; C18H23N2O3 requires 315.1703).
5.5. (2RS,4SR)-3-(2-Phenylpropionyl)-4,5,5-triphenyl-
oxazolidin-2-one rac-syn-19
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.48 mL, 2.5 M in hexane, 1.21 mmol), oxazolidin-2-one rac-14
(0.34 g, 1.10 mmol) and pentafluorophenyl 2-phenylpropionate
rac-8 (0.38 g, 1.21 mmol) gave a mixture of two diastereoisomeric
oxazolidin-2-ones 19 [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 oxazolidin-2-one (RS,SR)-syn-19 (0.26 g, 53%) as a white pow-
der; RF [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)]
0.69; mp = 160–165 °C; mmax (CHCl3) cmꢀ1 1780 (C@O) and 1704
(C@O); dH (400 MHz; CDCl3) 7.63 (2H, br d, J 7.7, 2 ꢂ CH; Ph),
7.46–7.36 (4H, m, 4 ꢂ CH; Ph), 7.19 (2H, dd, J 5.0, and 2.0,
2 ꢂ CH; Ph), 7.11–7.07 (2H, m, 2 ꢂ CH; Ph), 7.01–6.86 (8H, m,
8 ꢂ CH; Ph), 6.65 (2H, br d, J 7.7, 2 ꢂ 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 ꢂ i-C; 3 ꢂ 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 ꢂ CH; 4 ꢂ Ph), 88.5 (CPh2O), 66.0 (CHN),
44.0 (PhCHCH3) and 19.0 (PhCHCH3) (Found M+, 447.1835;
5.3. (2RS,4SR)-3-(2-Phenylpropionyl)-4-(4-hydroxyphenyl)-
oxazolidin-2-one rac-syn-17
In the same way10 as for oxazolidin-2-one 15, n-butyl lithium
(0.64 mL, 2.5 M in hexane, 1.61 mmol), oxazolidin-2-one rac-13
(0.132 g, 0.73 mmol) [derived from pre-mixing an equimolar
amount of (R)- and (S)-13] and pentafluorophenyl 2-phenylpropio-
nate rac-8 (0.25 g, 0.80 mmol) at ꢀ78 °C, then allowed to warm to
rt for over 12 h, gave a mixture of two diastereoisomeric oxazoli-
din-2-ones 17 [ratio 96:4: syn-:anti-]. The crude residue was puri-
fied by flash chromatography on silica gel eluting with light
petroleum ether (bp 40–60 °C)/diethyl ether (7:3) to give the oxaz-
olidin-2-one (RS,SR)-syn-17 (0.107 g, 50%) as a colourless crystal-
line solid; RF [light petroleum ether (bp 40–60 °C)/diethyl ether
(1:1)] 0.12; mp 150–152 °C; mmax (ethanol) cmꢀ1 1783 (C@O) and
1756 (C@O); dH (400 MHz; CDCl3) 7.16–7.11 (3H, m, 3 ꢂ CH; Ph),
7.04–6.99 (2H, m, 2 ꢂ CH; Ph), 6.73 (2H, dt, J 8.6 and 2.4, 2 ꢂ CH;
Ar), 6.55 (2H, dt, J 8.6 and 2.4, 2 ꢂ CH; Ar), 5.95 (1H, s, OH), 5.32
(1H, dd, J 9.0 and 5.0, CHN), 5.01 (1H, q, J 7.0, PhCHCH3), 4.54
(1H, t, J 9.0, CHAHBO), 4.00 (1H, dd, J 9.0 and 5.0, CHAHBO) and
1.33 (3H, d, J 7.0, PhCHCH3); dC (100 MHz; CDCl3) 173.8 (NC@O),
155.7 (i-CO; Ar), 153.1 (OC@O), 139.8 (i-C; Ph), 130.4 (i-C; Ar),
128.52, 128.12 and 127.11 (5 ꢂ CH; Ph), 127.52 and 115.62
C
30H25NO3 requires 447.1829); m/z 447 (10%, M+), 315 (5,
MꢀPh(CH3)C@C@O+), 256 (15, PhCHCPh2þ), 183 (20, Ph2C@OH+),
105 (100, PhCH@NH+) and 77 (20, Ph+).
6. Parallel kinetic resolution of pentafluorophenyl
2-phenylpropionate rac-8
6.1. Parallel kinetic resolution of pentafluorophenyl 2-phenyl-
propionate rac-8 using a quasi-enantiomeric combination of
oxazolidin-2-thione (R)-11 and oxazolidin-2-one (S)-1
(4 ꢂ CH; Ar), 69.7 (CH2O), 57.4 (CHN), 43.9 (PhCHCH3) and 18.6
þ
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.71 mL, 2.5 M in hexane, 1.78 mmol), 4-phenyl-oxazolidin-2-thi-
one (R)-11 (0.145 g, 0.81 mmol), 4-phenyl-oxazolidin-2-one (S)-1
(0.130 g, 0.81 mmol) and pentafluorophenyl 2-phenylpropionate
rac-8 (0.56 g, 1.78 mmol) gave a mixture of two diastereoisomeric
oxazolidin-2-thiones 15 [ratio 98:2: syn-:anti-] and two diastereo-
isomeric oxazolidin-2-ones 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 give the
(PhCHCH3) (Found MNH4
, 329.1493; C18H21N2O4 requires
329.1493); m/z 311 (20%, M+), 132 (100, Ph(CH3)C@C@O+) and
105 (40, PhCHCHþ3 ).
5.4. (2RS,4SR)-3-(2-Phenylpropionyl)-4-[4-(tert-butyl-
dimethylsilyloxy)phenyl]-oxazolidin-2-one rac-syn-18
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.48 mL, 2.5 M in hexane, 1.21 mmol), oxazolidin-2-one rac-2

1544
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
oxazolidin-2-thione (S,R)-syn-15 (0.14 g, 55%) as a white solid; RF
[light petroleum ether (bp 40–60 °C)/diethyl ether: (1:1)] 0.67;
M+ꢀPh(CH3)C@C@O), 256 (15, PhCHCPh2þ), 183 (20, Ph2C@OH+),
105 (100, PhCH@NH+) and 77 (20, Ph+).
mp 84–86 °C; ½a 2D5
ꢃ
¼ ꢀ58:3 (c 4.0, CHCl3);
m
max (CHCl3) cmꢀ1 1707
(C@S) and 1702 (C@O); dH (400 MHz; CDCl3) 7.20–7.08 (6H, m,
6 ꢂ CH; PhA and PhB), 6.94 (2H, dt, J 6.9 and 1.8, 2 ꢂ CH; PhA),
6.88 (2H, dt, J 7.0 and 1.8, 2 ꢂ CH; PhB), 5.98 (1H, q, J 6.9, PhCHCH3),
5.61 (1H, dd, J 9.2 and 6.1, CHN), 4.68 (1H, t, J 9.2, CHAHBO), 4.20 (1H,
dd, J 9.2 and 6.1, CHAHBO) and 1.35 (3H, d, J 6.9, PhCHCH3), dC
(100 MHz; CDCl3) 185.2 (C@S), 174.8 (C@O), 139.1 and 136.9
(2 ꢂ i-C; 2 ꢂ Ph), 128.8,2 128.7,1 128.5,2 128.3,2 127.11 and 126.42
(10 ꢂ CH; 2 ꢂ Ph), 73.6 (CH2O), 62.6 (CHN), 43.9 (PhCHCH3) and
18.7 (PhCHCH3) (Found MH+, 312.1054; C18H17NO2S requires
312.1053); and the oxazolidin-2-one (R,S)-syn-9 (0.14 g, 59%) as a
white solid; mp 124–126 °C; RF [light petroleum ether (bp 40–
6.3. Parallel kinetic resolution of pentafluorophenyl 2-phenyl-
propionate rac-8 using a quasi-enantiomeric combination of
oxazolidin-2-one (R)-2 and oxazolidin-2-one (S)-14
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.36 mL, 2.5 M in hexane, 0.902 mmol), 4-4-(tert-butyldimethyl-
silyloxy)phenyl-oxazolidin-2-one (R)-2 (0.12 g, 0.41 mmol), 4,5,5-
triphenyl-oxazolidin-2-one (S)-14 (0.13 g, 0.41 mmol) and penta-
fluorophenyl 2-phenylpropionate rac-8 (0.28 g, 0.902 mmol) gave
a mixture of two diastereoisomeric oxazolidin-2-ones (S,R)-18
(ratio >98:2: syn-:anti-) and (R,S)-19 (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 (2S,4R)-3-(2-phenylpropionyl)-4-[4-(tert-
60 °C)/diethyl ether (1:1)] 0.45; ½a D23
¼ ꢀ91:9 (c 4.9, CHCl3) {for
ꢃ
(S,R)-syn-9, lit.19
½
a 2D0
ꢃ
¼ þ88:5 (c 4.0, CHCl3)}; mmax (CHCl3)/
cmꢀ11778 (C@O) and 1701 (C@O); dH (400 MHz; CDCl3) 7.29–7.21
(10H, m, 10 ꢂ CH; 2 ꢂ 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 (C@O), 153.2 (C@O), 139.9 and 138.3
(2 ꢂ i-C; 2 ꢂ Ph), 128.9,2 128.5,3 128.2,2 127.11 and 125.92
(10 ꢂ CH; 2 ꢂ Ph), 69.6 (CH2O), 57.9 (NCH), 43.9 (PhCHCH3) and
18.6 (PhCHCH3) (Found MH+, 296.1286; C18H18NO3 requires
296.1287).
butyldimethylsilyloxy)-phenyl]-oxazolidin-2-one
(S,R)-syn-18
(0.141 g, 81%) as a cream crystalline solid; RF [light petroleum
ether (bp 40–60 °C)/diethyl ether (1:1)] 0.51; mp 96–98°C;
½
a 2D0
ꢃ
¼ þ89:1 (c 4.2, CHCl3); mmax (CHCl3) cmꢀ1 1779 (NC@O)
and 1706 (OC@O); dH (400 MHz; CDCl3) 7.14–7.10 (3H, m,
3 ꢂ CH; Ph), 7.01–6.96 (2H, m, 2 ꢂ CH; Ph), 6.74 (2H, dt, J 8.4
and 2.4, 2 ꢂ CH; Ar), 6.59 (2H, dt, J 8.4 and 2.4, 2 ꢂ CH; Ar),
5.31 (1H, dd, J 9.0 and 5.0, CHN), 4.99 (1H, q, J 7.0, PhCHCH3),
4.49 (1H, t, J 9.0, CHAHBO), 3.98 (1H, dd, J 9.0 and 5.0, CHAHBO),
1.30 (3H, d, J 7.0, PhCHCH3), 0.89 (9H, s, 3 ꢂ CH3C; t-Bu) and
0.10 (6H, s, 2 ꢂ CH3Si); dC (100 MHz; CDCl3) 173.5 (NC@O),
155.7 (i-CO; Ar), 153.0 (OC@O), 139.8 (i-C; Ph), 130.9 (i-C; Ar),
128.42, 128.02 and 126.91 (5 ꢂ CH; Ph), 127.22 and 120.22
(4 ꢂ CH; Ar), 69.6 (CH2O), 57.2 (CHN), 43.7 (PhCHCH3), 25.53
(3 ꢂ CH3C; t-Bu), 18.5 (PhCHCH3), 18.1 (CH3C; t-Bu), ꢀ4.5
ðCH3ASiCH3BÞ and ꢀ4.6 ðCH3ASiCH3BÞ (Found MH+, 426.2096;
6.2. Parallel kinetic resolution of pentafluorophenyl 2-phenyl-
propionate rac-8 using a quasi-enantiomeric combination of
oxazolidin-2-one (R)-1 and oxazolidin-2-one (S)-14
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.54 mL, 2.5 M in hexane, 1.34 mmol), 4-phenyl-oxazolidin-2-
one (R)-1 (0.10 g, 0.61 mmol), 4,5,5-triphenyl-oxazolidin-2-one
(S)-14 (0.19 g, 0.62 mmol) and pentafluorophenyl 2-phenylpropio-
nate rac-8 (0.42 g, 1.34 mmol) gave a mixture of two diastereoiso-
meric oxazolidin-2-ones (S,R)-9 (ratio >98:2: syn-:anti-) and (R,S)-
19 (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-9 (96 mg, 53%) as
a white solid; mp 140–142 °C; RF [light petroleum ether (bp 40–
60 °C)/diethyl ether (1:1)] 0.39; mmax (CHCl3) cmꢀ11778 (C@O)
C
24H32NO4Si requires 426.2095); m/z 425 (20%, M+), 132 (70,
Ph(CH3)C@C@O+) and 105 (100, PhCHCHþ3 ); and (2R,4S)-3-(2-
phenylpropionyl)-4,5,5-triphenyl-oxazolidin-2-one (R,S)-syn-19
(0.14 g, 73%); RF [light petroleum ether (bp 40–60 °C)/diethyl
ether (1:1)] 0.69, which was spectroscopically identical to that
reported previously.
6.4. Parallel kinetic resolution of pentafluorophenyl 2-
phenylpropionate rac-8 using a quasi-enantiomeric
combination of oxazolidin-2-one (R)-13 and oxazolidin-2-one
(S)-14
and 1701 (C@O); ½a D20
ꢃ
¼ þ92:5 (c 4.9, CHCl3); {lit.19
½
a 2D0
ꢃ
¼ þ88:5
(c 4.0, CHCl3)}; dH (400 MHz; CDCl3) 7.29–7.21 (10H, m, 10 ꢂ CH;
2 ꢂ 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 ꢂ CH; 2 ꢂ Ph), 69.6
(CH2O), 57.9 (CHN), 43.9 (PhCHCH3) and 18.6 (PhCHCH3) (Found
In the same way10 as for oxazolidin-2-one 15, n-butyl lithium
(0.74 mL, 2.5 M in hexane, 1.85 mmol), 4-(4-hydroxyphenyl)-oxaz-
olidin-2-one (R)-13 (0.10 g, 0.55 mmol), 4,5,5-triphenyl-oxazo-
lidin-2-one (S)-14 (0.175 g, 0.55 mmol) and pentafluorophenyl
2-phenylpropionate rac-8 (0.41 g, 1.28 mmol) at ꢀ78 °C, then
allowed to warm to rt over 12 h, gave a mixture of two diastereo-
isomeric oxazolidin-2-one (S,R)-17 (ratio >97:3: syn-:anti-) and
oxazolidin-2-one (R,S)-19 (ratio 92:8: syn-:anti-). The crude resi-
due 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-phenylpropionyl)-4-(4-hydroxyphenyl)-oxazolidin-2-
one (S,R)-syn-17 (78 mg, 46%) as a colourless crystalline solid; RF
[light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.12;
MH+, 296.1286; C15H18NOþ requires 296.1287); and (2R,4S)-3-(2-
3
phenylpropionyl)-4,5,5-triphenyl-oxazolidin-2-one
(R,S)-syn-19
(0.14 g, 50%) as a white powder; RF [light petroleum ether (bp
40–60 °C)/diethyl
ether
(1:1)]
0.69;
mp
154–156 °C;
½
a 2D0
ꢃ
¼ ꢀ255:1 (c 3.4, CHCl3); mmax (CHCl3) cmꢀ1 1780 (C@O) and
1704 (C@O); dH (400 MHz; CDCl3) 7.63 (2H, br d, J 7.7, 2 ꢂ CH;
Ph), 7.46–7.36 (4H, m, 4 ꢂ CH; Ph), 7.19 (2H, br dd, J 5.0, and 2.0,
2 ꢂ CH; Ph), 7.11–7.07 (2H, m, 2 ꢂ CH; Ph), 7.01–6.86 (8H, m,
8 ꢂ CH; Ph), 6.65 (2H, br d, J 7.7, 2 ꢂ 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 ꢂ i-C; 3 ꢂ 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 ꢂ CH; 4 ꢂ Ph), 88.5 (CPh2O), 66.0 (CHN),
44.0 (PhCHCH3) and 19.0 (PhCHCH3) (Found MNa+, 448.1912;
mp 135–137 °C; ½a D20
ꢃ
¼ þ81:2 (c 1.3, CHCl3); ½a D20
¼ þ77:2 (c 1.3,
ꢃ
ethanol); mmax (ethanol) cmꢀ1 1783 (NC@O) and 1756 (OC@O); dH
(400 MHz; CDCl3) 7.16–7.11 (3H, m, 3 ꢂ CH; Ph), 7.04–6.99 (2H,
m, 2 ꢂ CH; Ph), 6.73 (2H, dt, J 8.6 and 2.4, 2 ꢂ CH; Ar), 6.55 (2H,
dt, J 8.6 and 2.4, 2 ꢂ CH; Ar), 5.95 (1H, s, OH), 5.32 (1H, dd, J 9.0
and 5.0, CHN), 5.01 (1H, q, J 7.0, PhCHCH3), 4.54 (1H, t, J 9.0, CHAH-
BO), 4.00 (1H, dd, J 9.0 and 5.0, CHAHBO) and 1.33 (3H, d, J 7.0,
PhCHCH3); dC (100 MHz; CDCl3) 173.8 (NC@O), 155.7 (i-CO; Ar),
C
24H31NO4SiNa requires 448.1915); m/z 447 (10%, M+), 315 (5,

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
1545
153.1 (OC@O), 139.8 (i-C; Ph), 130.4 (i-C; Ar), 128.52, 128.12 and
pionyl)-4-(4-hydroxyphenyl)-oxazolidin-2-one
(R,S)-syn-17
127.11 (5 ꢂ CH; Ph), 127.52 and 115.62 (4 ꢂ CH; Ar), 69.7 (CH2O),
(0.10 g, 53%) as a white crystalline solid;RF [light petroleum ether
(bp 40–60 °C)/diethyl ether (1:1)] 0.12, which was spectroscopi-
cally identical to that reported previously.
þ
57.4 (CHN), 43.9 (PhCHCH3) and 18.6 (PhCHCH3) (Found MNH4
,
329.1493; C18H21N2O2 requires 329.1496); m/z 311 (20%, M+),
132 (100, Ph(CH3)C@C@O+) and 105 (40, PhCHCHþ3 ); and (2R,4S)-
3-(2-phenylpropionyl)-4,5,5-triphenyl-oxazolidin-2-one (R,S)-syn-
19 (0.142 g, 58%); RF [light petroleum ether (bp 40–60 °C)/diethyl
ether (1:1)] 0.51, which was spectroscopically identical to that re-
ported previously.
6.7. Parallel kinetic resolution of pentafluorophenyl 2-phenyl-
propionate rac-8 using a quasi-enantiomeric combination of
oxazolidin-2-one (R)-13 and oxazolidin-2-one (S)-1
In the same way10 as for oxazolidin-2-one 15, n-butyl lithium
(0.81 mL, 2.5 M in hexane, 2.02 mmol), 4-hydroxyphenyl-oxazoli-
din-2-one (R)-13 (0.11 g, 0.61 mmol), 4-phenyl-oxazolidin-2-one
(S)-1 (0.10 g, 0.61 mmol) and pentafluorophenyl 2-phenylpropio-
nate rac-8 (0.446 g, 1.41 mmol) at ꢀ78 °C, then allowed to warm
to rt over 12 h, gave a mixture of two diastereoisomeric oxazoli-
din-2-ones (S,R)-17 (ratio 95:5: syn-:anti-) and (R,S)-9 (ratio
93:7: 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-phenylpropionyl)-
4-(4-hydroxyphenyl)-oxazolidin-2-one (S,R)-syn-17 (0.106 g, 56%)
as a white solid; RF [light petroleum ether (bp 40–60 °C)/diethyl
ether (1:1)] 0.12, which was spectroscopically identical to that re-
ported previously; and (2R,4S)-3-(2-phenyl-propionyl)-4-phenyl-
oxazolidin-2-one (R,S)-syn-9 (0.148 g, 82%) as a white solid; mp
124–126 °C; RF [light petroleum ether (bp 40–60 °C)/diethyl ether
6.5. Parallel kinetic resolution of pentafluorophenyl 2-phenyl-
propionate rac-8 using a quasi-enantiomeric combination of
oxazolidin-2-one (R)-1 and oxazolidin-2-one (S)-2
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.53 mL, 2.5 M in hexane, 1.34 mmol), 4 phenyl-oxazolidin-2-
one (R)-1 (0.10 g, 0.61 mmol), 4-(tert-butyldimethylsilyl-
oxy)phenyl-oxazolidin-2-one (S)-2 (0.18 g, 0.61 mmol) and penta-
fluorophenyl 2-phenylpropionate rac-8 (0.42 g, 1.34 mmol) gave a
mixture of two diastereoisomeric oxazolidin-2-ones (S,R)-9 (ratio
>98:2: syn-:anti-) and (R,S)-18 (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)-4-phenyl-3-(2-phenyl-propionyl)oxazolidin-2-one
(S,R)-syn-9 (0.12 g, 68%) as a white solid; RF [light petroleum ether
(bp 40–60 °C)/diethyl ether (1:1)] 0.39, which was spectro-
scopically identical to that reported previously; and (2R,4S)-3-(2-
phenylpropionyl)-4-[4-(tert-butyldimethylsilyloxy)phenyl]-oxazo-
lidin-2-one (R,S)-syn-18 (0.19 g, 68%) as a white crystalline solid;
RF [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.51;
(1:1)] 0.39;
½
a 2D3
ꢃ
¼ ꢀ91:9 (c 4.9, CHCl3) {lit.19 (S,R)-syn-9;
½
a 2D0
ꢃ
¼ þ88:5 (c 4.0, CHCl3)}; mmax (CHCl3) cmꢀ11778 (C@O) and
1701 (C@O); dH (400 MHz; CDCl3) 7.29–7.21 (10H, m, 10 ꢂ CH;
2 ꢂ 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 (C@O), 153.2 (C@O), 139.9 and 138.3 (2 ꢂ i-C; 2 ꢂ Ph),
128.9,2 128.5,3 128.2,2 127.11 and 125.92 (10 ꢂ CH; 2 ꢂ Ph), 69.6
(CH2O), 57.9 (CHN), 43.9 (PhCHCH3) and 18.6 (PhCHCH3) (Found
MH+, 296.1286; C18H18NO3 requires 296.1287).
mp 96–98 °C; ½a 2D0
ꢃ
¼ ꢀ95:2 (c 2.0, CHCl3); mmax (CHCl3) cmꢀ1
1779 (NC@O) and 1706 (OC@O); dH (400 MHz; CDCl3) 7.14–7.10
(3H, m, 3 ꢂ CH; Ph), 7.01–6.96 (2H, m, 2 ꢂ CH; Ph), 6.74 (2H, dt, J
8.4 and 2.4, 2 ꢂ CH; Ar), 6.59 (2H, dt, J 8.4 and 2.4, 2 ꢂ CH; Ar),
5.31 (1H, dd, J 9.0 and 5.0, CHN), 4.99 (1H, q, J 7.0, PhCHCH3),
4.49 (1H, t, J 9.0, CHAHBO), 3.98 (1H, dd, J 9.0 and 5.0, CHAHBO),
1.30 (3H, d, J 7.0, PhCHCH3), 0.89 (9H, s, 3 ꢂ CH3C; t-Bu) and 0.10
(6H, s, 2 ꢂ CH3Si); dC (100 MHz; CDCl3) 173.5 (NC@O), 155.7 (i-C;
Ar), 153.0 (OC@O), 139.8 (i-C; Ph), 130.9 (i-C; Ar), 128.42, 128.02
and 126.91 (5 ꢂ CH; Ph), 127.22 and 120.22 (4 ꢂ CH; Ar), 69.6
(CH2O), 57.2 (CHN), 43.7 (PhCHCH3), 25.53 (3 ꢂ CH3C; t-Bu), 18.5
(PhCHCH3), 18.1 (CH3C; t-Bu), ꢀ4.5 ðCHA3 SiCH3BÞ and ꢀ4.6
ðCHA3 SiCHB3Þ; (Found MNa+, 448.1912; C24H31NO4SiNa requires
448.1915); m/z 425 (10%, M+), 132 (60, Ph(CH3)C@C@O+) and 105
(100, PhCHCHþ3 ).
6.8. Parallel kinetic resolution of pentafluorophenyl 2-phenyl-
propionate rac-8 using a quasi-enantiomeric combination of
oxazolidin-2-one (R)-2 and oxazolidin-2-one (S)-13
In the same way10 as for oxazolidin-2-one 15, n-butyl lithium
(0.45 mL, 2.5 M in hexane, 1.12 mmol), 4-(tert-butyldimethylsilyl-
oxy)phenyl-oxazolidin-2-one (R)-2 (0.10 g, 0.34 mmol), 4-
hydroxyphenyl-oxazolidin-2-one (S)-13 (61 mg, 0.34 mmol) and
pentafluorophenyl 2-phenylpropionate rac-8 (0.23 g, 0.78 mmol)
at ꢀ78 °C, then allowed to warm to rt over 12 h, gave a mixture
of two diastereoisomeric oxazolidin-2-ones (S,R)-18 (ratio 98:2:
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-phenylpropionyl)-4-[4-(tert-butyldimethylsilyloxy)-
phenyl]-oxazolidin-2-one (S,R)-syn-18 (88 mg, 61%) as a white so-
lid; RF [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)]
0.51, which was spectroscopically identical to that reported previ-
ously; and (2R,4S)-3-(2-phenylpropionyl)-4-(4-hydroxyphenyl)-
oxazolidin-2-one (R,S)-syn-17 (51 mg, 49%) as a colourless crystal-
line solid; RF [light petroleum ether (bp 40–60 °C)/diethyl ether
6.6. Parallel kinetic resolution of pentafluorophenyl 2-phenyl-
propionate rac-8 using a quasi-enantiomeric combination of
oxazolidin-2-one (R)-1 and oxazolidin-2-one (S)-2 (involving a
TBAF purification step)
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.53 mL, 2.5 M in hexane, 1.34 mmol), 4 phenyl-oxazolidin-2-
one (R)-1 (0.10 g, 0.61 mmol), 4-(tert-butyldimethylsilyloxy)-
phenyl-oxazolidin-2-one (S)-2 (0.18 g, 0.61 mmol), pentafluoro-
phenyl 2-phenylpropionate rac-8 (0.42 g, 1.34 mmol), followed
by the addition of TBAF (1.82 mL, 1 M in THF, 1.83 mmol) after
2 h, and stirring the resulting solution at rt for 2 h, gave a mixture
of two diastereoisomeric oxazolidin-2-ones (S,R)-9 (ratio >98:2:
syn-:anti-) and (R,S)-18 (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)-4-phenyl-3-(2-phenyl-propionyl)oxazolidin-2-one (S,R)-
syn-9 (0.10 g, 58%) as a white solid; RF [light petroleum ether (bp
40–60 °C)/diethyl ether (1:1)] 0.39, which was spectroscopically
identical to that reported previously; and (2R,4S)-3-(2-phenylpro-
(1:1)] 0.12; mp 135–137 °C; ½a D20
¼ ꢀ78:6 (c 2.5, CHCl3); {(S,R)-
ꢃ
17; ½a 2D0
ꢃ
¼ þ81:2 (c 1.3, CHCl3)}; mmax (ethanol) cmꢀ1 1783 (C@O)
and 1756 (C@O); dH (400 MHz; CDCl3) 7.16–7.11 (3H, m, 3 ꢂ CH;
Ph), 7.04–6.99 (2H, m, 2 ꢂ CH; Ph), 6.73 (2H, dt, J 8.6 and 2.4,
2 ꢂ CH; Ar), 6.55 (2H, dt, J 8.6 and 2.4, 2 ꢂ CH; Ar), 5.95 (1H, br
s, OH), 5.32 (1H, dd, J 9.0 and 5.0, CHN), 5.01 (1H, q, J 7.0,
PhCHCH3), 4.54 (1H, t, J 9.0, CHAHBO), 4.00 (1H, dd, J 9.0 and 5.0,
CHAHBO) and 1.33 (3H, d, J 7.0, PhCHCH3); dC (100 MHz; CDCl3)
173.8 (NC@O), 155.7 (i-CO; Ar), 153.1 (OC@O), 139.8 (i-C; Ph),

1546
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
130.4 (i-C; Ar), 128.52, 128.12 and 127.11 (5 ꢂ CH; Ph), 127.52 and
115.62 (4 ꢂ CH; Ar), 69.7 (CH2O), 57.4 (CHN), 43.9 (PhCHCH3) and
18.6 (PhCHCH3) (Found MNH4þ, 329.1493; C18H21N2O2 requires
329.1493).
1.496 mmol) gave a mixture of two diastereoisomeric oxazoli-
din-2-ones (S,R)-25 (ratio 97:3: syn-:anti-) and (R,S)-29 (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-[(4-methylphenyl)pro-
pionyl]-4-phenyl-oxazolidin-2-one (S,R)-syn-25 (0.14 g, 69%) as a
white solid; RF [light petroleum ether (bp 40–60 °C)/diethyl ether
(1:1)] 0.39; mp 105–110 °C {for (R,S)-syn-25; mp 105–110 °C};
7. Parallel kinetic resolution of active esters rac-20–23 using a
quasi-enantiomeric combination of oxazolidin-2-ones (R)-1
and (S)-2
mmax (CHCl3) cmꢀ1 1780 (C@O) and 1700 (C@O); ½a 2D0
¼ þ121:6
ꢃ
(c 0.6, CHCl3) {for (R,S)-syn-25; ½a D20
¼ ꢀ116:5 (c 0.8, CHCl3)}; dH
ꢃ
7.1. Parallel kinetic resolution of pentafluorophenyl 2-phenyl-
butanoate rac-20 using a quasi-enantiomeric combination of
oxazolidin-2-one (R)-1 and oxazolidin-2-one (S)-2
(400 MHz, CDCl3) 7.21–7.12 (3H, m, 3 ꢂ CH; Ph), 6.96 (2H, br d,
J 8.2, 2 ꢂ CH; Ar), 6.90 (2H, br d, J 8.2, 2 ꢂ CH; Ar), 6.86 (2H, d,
J 6.9, 2 ꢂ 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 ꢂ CH; Ph and Ar), 69.6 (CH2O),
57.8 (CHN), 43.2 (ArCHCH3), 21.0 (CH3; Ar) and 18.7 (ArCHCH3)
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.59 mL, 2.5 M in hexane, 1.496 mmol), 4-phenyl-oxazolidin-2-
one (R)-1 (0.11 g, 0.68 mmol), 4-(tert-butyldimethylsilyl-
oxy)phenyl-oxazolidin-2-one (S)-2 (0.20 g, 0.68 mmol) and penta-
fluorophenyl 2-phenylbutanoate rac-20 (0.49 g, 1.49 mmol) gave a
mixture of two diastereoisomeric oxazolidin-2-ones (S,R)-24 (ratio
>98:2: syn-:anti-) and (R,S)-28 (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
(Found MNH4þ, 327.1701; C19H23N2Oþ requires 327.1709); and
3
(2R,4S)-3-[2-(4-methylphenyl)propionyl]-4-[4-(tert-butyldimeth-
ylsiloxyloxy)phenyl]-oxazolidin-2-one (R,S)-syn-29 (0.21 g, 72%)
as a colourless oil; RF [light petroleum ether (bp 40–60 °C)/diethyl
ether (1:1)] 0.62; ½a D20
ꢃ
¼ ꢀ120:3 (c 6.0, CHCl3); mmax (CH2Cl2)
give
(2S,4R)-3-(2-phenylbutanoyl)-4-phenyl-oxazolidin-2-one
cmꢀ1 1773 (C@O) and 1704 (C@O); dH (400 MHz; CDCl3) 6.98
(2H, br d, J 8.0, 2 ꢂ CH; ArA), 6.91 (2H, dt, J 8.0 and 1.8, 2 ꢂ CH;
ArA), 6.79 (2H, dt, J 8.5 and 2.5, 2 ꢂ CH; ArB), 6.63 (2H, dt, J 8.5
and 2.5, 2 ꢂ CH; ArB), 5.35 (1H, dd, J 8.9 and 4.9, CHN), 4.99
(1H, q, J 6.9, ArCHCH3), 4.56 (1H, t, J 8.9, CHAHBO), 4.05 (1H, dd,
J 8.9 and 4.9, CHAHBO), 2.27 (3H, s, CH3; ArA), 1.33 (3H, d, J 6.9,
ArCHCH3), 0.94 (9H, s, 3 ꢂ CH3; t-Bu) and 0.15 (6H, s, 2 ꢂ SiCH3);
dC (100 MHz; CDCl3) 173.8 (NC@O), 155.8 (OC@O), 153.1 (i-CO;
ArB), 136.9, 136.6 and 130.9 (3 ꢂ i-C; ArA and ArB), 129.1, 128.0,
127.4 and 120.2 (4 ꢂ CH; ArAand ArB), 69.7 (CH2O), 57.3 (CHN),
43.4 (ArCHCH3), 25.63 (3 ꢂ CH3; t-Bu), 21.0 (CH3; ArA), 18.7
(ArCHCH3), 18.2 (CH3C; t-Bu) and ꢀ4.52 (2 ꢂ SiCH3) (Found
MNH4þ, 457.2513; C25H37N2O4Si requires 457.2517).
(S,R)-syn-24 (0.15 g, 71%) as a white solid; mp 82–84 °C; RF [light
petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.40;
½
a 2D0
ꢃ
¼ þ77:4 (c 4.0, CHCl3); mmax (CH2Cl2) cmꢀ1 1772 (C@O) and
1700 (C@O); dH (400 MHz; CDCl3) 7.17–7.09 (6H, m, 6 ꢂ CH; Ph),
7.04–7.02 (2H, m, 2 ꢂ CH; Ph), 6.81–6.79 (2H, m, 2 ꢂ 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 (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 ꢂ 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 310.1443); and (2R,3S)-3-(2-phenyl-
butanoyl)-4-[4-(tert-butyldimethylsilanyloxy)phenyl]-oxazolidin-
2-one (R,S)-syn-28 (0.18 g, 62%) as a colourless oil; RF [light petro-
7.3. Parallel kinetic resolution of pentafluorophenyl 2-(4-
chlorophenyl)propionate rac-22 using a quasi-enantiomeric
combination of oxazolidin-2-one (R)-1 and oxazolidin-2-one
(S)-2
leum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.69; ½a D20
¼ ꢀ89:4 (c
ꢃ
4.4, CHCl3); mmax (CH2Cl2) cmꢀ1 1778 (C@O) and 1709 (C@O); dH
(400 MHz; CDCl3) 7.19–7.15 (3H, m, 3 ꢂ CH; Ph), 7.07–7.04 (2H,
m, 2 ꢂ CH; Ph), 6.75 (2H, dt, J 8.5 and 2.5, 2 ꢂ CH; Ar), 6.61 (2H,
dt, J 8.5 and 2.5, 2 ꢂ CH; Ar), 5.37 (1H, dd, J 8.9 and 5.0, CHN),
4.84 (1H, t, J 7.5, PhCH), 4.56 (1H, t, J 8.9, CHAHBO), 4.03 (1H, dd,
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.59 mL, 2.5 M in hexane, 1.496 mmol), 4-phenyl-oxazolidin-2-
one (R)-1 (0.11 g, 0.68 mmol), 4-(tert-butyldimethylsilyl-
oxy)phenyl-oxazolidin-2-one (S)-2 (0.20 g, 0.68 mmol) and penta-
J
8.9 and 5.0, CHAHBO), 2.00 (1H, dquint, J 13.8 and 7.3,
CHACHBCH3), 1.66 (1H, dquint, J 13.8 and 7.3, CHACHBCH3), 0.94
(9H, s, 3 ꢂ CH3; t-Bu), 0.83 (3H, t, J 7.3, CH3CH2), 0.15 (6H, s,
2 ꢂ SiCH3); dC (100 MHz; CDCl3) 173.0 (NC@O), 155.7 (OC@O),
153.1 (i-CO; Ar), 138.1 (i-C; Ph) 130.9 (i-C; Ar), 128.6,2 128.3,2
127.1,2 127.01 and 120.22 (9 ꢂ CH; Phand Ar), 69.6 (CH2O), 57.3
(CHN), 51.1 (PhCH), 26.2 (CH2CH3), 25.63 (3 ꢂ CH3; t-Bu), 18.1
(CH3C; t-Bu), 11.9 (CH2CH3) and ꢀ4.52 (2 ꢂ SiCH3) (Found
MNH4þ, 447.2218; C25H37N2O4Si requires 447.2217).
fluorophenyl
2-(4-chlorophenyl)propionate
rac-22
(0.52 g,
1.496 mmol) gave a mixture of two diastereoisomeric oxazolidin-
2-ones (S,R)-26 (ratio 97:3: syn-:anti-) and (R,S)-30 (ratio 97:3:
syn-:anti-). The crude residue was purified by flash chromatogra-
phy on silica gel eluting with light petroleum ether (bp 40–
60 °C)/diethyl ether (7:3) to give (2S,4R)-3-[(4-chlorophenyl)propi-
onyl]-4-phenyl-oxazolidin-2-one (S,R)-syn-26 (0.11 g, 50%) 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-26; mp 142–144 °C};
mmax (CHCl3) cmꢀ1 1782 (C@O) and 1700 (C@O); ½a 2D0
¼ þ144:4 (c
ꢃ
7.2. Parallel kinetic resolution of pentafluorophenyl 2-(4-
methylphenyl)propionate rac-21 using a quasi-enantiomeric
combination of oxazolidin-2-one (R)-1 and oxazolidin-2-one
(S)-2
1.6, CHCl3) {for (R,S)-syn-26; ½a D20
¼ ꢀ142:4 (c 1.5, CHCl3)}; dH
ꢃ
(400 MHz, CDCl3) 7.32–7.22 (3H, m, 3 ꢂ CH; Ph), 7.18 (2H, dt, J
8.5 and 2.2, 2 ꢂ CH; Ar), 7.01 (2H, dt, J 8.5 and 2.2, 2 ꢂ CH; Ar),
6.95 (2H, dt, J 6.8 and 1.5, 2 ꢂ 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 ꢂ CH; 2 ꢂ Ar), 69.4 (CH2O), 57.9 (CHN), 43.8
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.59 mL, 2.5 M in hexane, 1.496 mmol), 4-phenyl-oxazolidin-2-
one (R)-1 (0.11 g, 0.68 mmol), 4-(tert-butyldimethylsilyl-
oxy)phenyl-oxazolidin-2-one (S)-2 (0.20 g, 0.68 mmol) and penta-
fluorophenyl 2-(4-methylphenyl)propionate rac-21 (0.49 g,

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
1547
(ArCHCH3) and 18.9 (ArCHCH3) (Found M(35Cl)+ 329.0815;
173.8 (NC@O), 155.7 (OC@O), 153.1 (i-CO; Ar), 140.4, 136.9 and
130.9 (3 ꢂ i-C; ArA and ArB), 129.1, 127.8, 127.2 and 120.2
(4 ꢂ CH; ArAand ArB), 69.6 (CH2O), 57.2 (CHN), 45.0 (CH2Ar), 43.3
(ArCHCH3), 30.2 ((CH3)2CH), 25.63 (3 ꢂ CH3; t-Bu), 22.4 and 22.3
C
18H16ClNOþ requires 329.0813); and (2R,4S)-3-[(4-chloro-
3
phenyl)propionyl]-4-[4-(tert-butyldimethylsilyloxy)phenyl]-oxaz-
olidin-2-one (R,S)-syn-30 (0.16 g, 53%) as a white solid; RF [light
petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.44; mp 103–
(2 ꢂ CH3; i-Bu), 18.4 (ArCHCH3), 18.1 (CH3C; t-Bu) and ꢀ4.52
107 °C; ½a 2D0
ꢃ
¼ ꢀ130:8 (c 4.2, CHCl3); mmax (CH2Cl2) cmꢀ1 1781
(2 ꢂ SiCH3) (Found MNH4
, 499.2980; C28H43N2O4Si requires
þ
(C@O) and 1712 (C@O); dH (400 MHz; CDCl3) 7.13 (2H, dt, J 8.6
and 2.5, 2 ꢂ CH; ArA), 6.95 (2H, dt, J 8.6 and 2.5, 2 ꢂ CH; ArA),
6.80 (2H, dt, J 8.6 and 2.9, 2 ꢂ CH; ArB), 6.65 (2H, dt, J 8.6 and
2.9, 2 ꢂ CH; ArB), 5.35 (1H, dd, J 9.0 and 4.8, CHN), 5.00 (1H, q, J
6.9, ArCHCH3), 4.57 (1H, t, J 9.0, CHAHBO), 4.07 (1H, dd, J 9.0 and
4.8, CHAHBO), 1.32 (3H, d, J 6.9, ArCHCH3), 0.94 (9H, s, 3 ꢂ CH3; t-
Bu) and 0.15 (6H, s, 2 ꢂ SiCH3); dC (100 MHz; CDCl3) 173.2 (NC@O),
155.9 (OC@O), 153.0 (i-CO; ArB), 138.4 (i-CCl; Ar), 132.9 and 130.8
(2 ꢂ i-C; ArA and ArB), 129.5, 128.6, 127.3 and 120.4 (4 ꢂ CH; ArA
and ArB), 69.7 (CH2O), 57.3 (CHN), 43.2 (ArCHCH3), 25.63
(3 ꢂ CH3; t-Bu), 18.5 (ArCHCH3), 18.2 (CH3C; t-Bu) and ꢀ4.62
(2 ꢂ SiCH3) (Found M(35Cl)+, 459.1620; C24H30ClNO4Si requires
459.1620).
499.2987).
7.5. (+)-2-Phenylpropionic acid (S)-32 hydrolysis of oxazolidin-
2-one adduct (S,R)-syn-9
Lithium hydroxide monohydrate (71 mg, 1.71 mmol) was
slowly added to a stirred solution of oxazolidin-2-one (R,S)-syn-9
(0.15 g, 0.57 mmol) and hydrogen peroxide (58 mg, 0.48 mL,
1.71 mmol, 40%/w) in THF/water (3:1; 4 mL). The reaction mixture
was stirred at room temperature for 12 h. The reaction was
quenched with water (10 mL) and extracted with dichloromethane
(3 ꢂ 10 mL). The combined organic layers were dried over MgSO4
and evaporated under reduced pressure to give the recovered
oxazolidin-2-one (R)-1 (80 mg, 87%) as
a
white solid;
¼ þ49:5 (c 2.1,
7.4. Parallel kinetic resolution of pentafluorophenyl 2-(4-
isobutylphenyl)propionate rac-23 using a quasi-enantiomeric
combination of oxazolidin-2-one (R)-1 and oxazolidin-2-one
(S)-2
½
a 2D0
ꢃ
¼ ꢀ48:3 (c 2.0, CHCl3), {for (S)-; lit.17
½
a 2D0
ꢃ
CHCl3)}; and 2-phenylpropionic acid (+)-(S)-32 (78 mg, 92%) as col-
ourless 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.17
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 ꢂ 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),
139.7 (i-C; Ph), 128.7,2 127.62 and 127.41 (5 ꢂ CH; Ph), 45.3
In the same way as for oxazolidin-2-one 15, n-butyl lithium
(0.59 mL, 2.5 M in hexane, 1.496 mmol), 4-phenyl-oxazolidin-2-
one (R)-1 (0.11 g, 0.68 mmol), 4-(tert-butyldimethylsilyl-
oxy)phenyl-oxazolidin-2-one (S)-2 (0.20 g, 0.68 mmol) and penta-
fluorophenyl 2-(4-isobutylphenyl)propionate rac-23 (0.56 g,
1.496 mmol) gave a mixture of two diastereoisomeric oxazolidin-
2-ones (S,R)-27 (ratio >98:2: syn-:anti-) and (R,S)-31 (ratio >98:2:
syn-:anti-). The crude residue was purified by flash chromatogra-
phy on silica gel eluting with light petroleum ether (bp 40–
60 °C)/diethyl ether (7:3) to give (2S,4R)-3-[(4-isobutylphenyl)pro-
pionyl]-4-phenyl-oxazolidin-2-one (S,R)-syn-27 (0.167 g, 70%) as a
white solid; mp 86–88 °C; RF [light petroleum ether (bp 40–60 °C)/
(PhCHCH3) and 18.1 (PhCHCH3) (Found MH+ 151.0753. C9H11NOþ
2
requires 151.0759).
7.6. Hydrolysis of oxazolidin-2-one adduct (R,S)-syn-17
In the same way as above, lithium hydroxide monohydrate
(60 mg, 1.43 mmol), hydrogen peroxide (48 mg, 0.40 mL,
1.43 mmol, 40%/w) and oxazolidin-2-one (R,S)-syn-17 (0.11 g,
0.36 mmol) in THF/water (3:1; 4 mL) gave after an acidic extrac-
tion, 2-phenylpropionic acid (ꢀ)-(R)-32 (48 mg, 90%) as a colour-
diethyl ether (1:1)] 0.41; ½a D25
¼ þ118:7 (c 6.0, CHCl3) {for (R,S)-
ꢃ
syn-27; lit.18
½
a 2D5
ꢃ
¼ ꢀ114:6 (c 4.2, CHCl3); mmax (CHCl3)
less oil; ½a 2D0
ꢃ
¼ ꢀ69:5 (c 1.0, CHCl3) {lit.19
½
a 2D2
ꢃ
¼ ꢀ71:2 (c 0.66,
cmꢀ11779 (C@O) and 1705 (C@O); dH (400 MHz; CDCl3) 7.28–
7.15 (3H, m, 3 ꢂ CH; Ph), 7.00 (4H, m, 4 ꢂ CH, Ph and Ar), 6.90
(2H, dt, J 7.9 and 1.9, 2 ꢂ 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, nonet, J 6.8, (CH3)2CH), 1.38 (3H, d, J 6.9, ArCHCH3),
0.90 (3H, d, J 6.6, CHACHCHB) and 0.89 (3H, d, J 6.6, CHACHCHB); dC
CHCl3)}, which was spectroscopically identical to that reported
previously.
7.7. Hydrolysis of oxazolidin-2-one adduct (R,S)-syn-18
In the same way as above, lithium hydroxide monohydrate
(53 mg, 1.24 mmol), hydrogen peroxide (42 mg, 0.35 mL,
1.24 mmol, 40%/w) and oxazolidin-2-one (R,S)-syn-18 (0.132 g,
0.31 mmol) in THF/water (3:1; 4 mL) gave after an acidic extrac-
tion, 2-phenylpropionic acid (ꢀ)-(R)-32 (41 mg, 90%) as a colour-
3
3
3
3
(100.6 MHz; CDCl3) 174.3 (NC@O), 153.3 (OC@O), 140.7 (i-C; Ar),
139.4 (i-C; Ar), 137.4 (i-C; Ph), 129.32 and 127.92 (4 ꢂ CH; Ar),
128.8,2 128.51 and 125.82 (5 ꢂ 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
352.1907); m/z 351.1 (10% M+), 188.1 (10, Ar(CH3)C@C@O+),
161.1 (10, Ar+CHCH3), 145.1 (100, ArCHþ2 ) and 77.1 (10, Ph+) (Found
MNH4þ, 369.2171; C22H29N2O3 requires 369.2173); and (2R,4S)-
3-[(4-isobutylphenyl)propionyl]-4-[4-(tert-butyldimethylsilyloxy)-
phenyl]-oxazolidin-2-one (R,S)-syn-31 (0.23 g, 72%) as a white
solid; RF [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)]
less oil; ½a 2D0
ꢃ
¼ ꢀ71:4 (c 0.7, CHCl3) {lit.19
½
a 2D2
ꢃ
¼ ꢀ71:2 (c 0.66,
CHCl3)}, which was spectroscopically identical to that reported
previously.
7.8. Hydrolysis of oxazolidin-2-one adduct (R,S)-syn-19
In the same way as above, lithium hydroxide monohydrate
(13 mg, 0.30 mmol), hydrogen peroxide (10 mg, 80 lL, 0.30 mmol,
40%/w) and oxazolidin-2-one (R,S)-syn-19 (67 mg, 0.15 mmol) in
0.65; mp 68–70 °C; ½a D20
ꢃ
¼ ꢀ129:6 (c 3.4, CHCl3); mmax (CH2Cl2)
cmꢀ1 1780 (C@O) and 1707 (C@O); dH (400 MHz; CDCl3) 6.96
(4H, br s, 4 ꢂ CH; ArA), 6.74 (2H, dt, J 8.4 and 2.4, 2 ꢂ CH; ArB),
6.61 (2H, dt, J 8.4 and 2.4, 2 ꢂ CH; ArB), 5.37 (1H, dd, J 8.8 and
5.1, CHN), 5.05 (1H, q, J 6.9, ArCHCH3), 4.56 (1H, t, J 8.8, CHAHBO),
4.03 (1H, dd, J 8.8 and 5.1, CHAHBO), 2.40 (2H, d, J 6.8, CH2Ar), 1.82
(1H, nonet, J 6.8, (CH3)2CH), 1.35 (3H, d, J 7.1, ArCHCH3), 0.95 (9H, s,
3 ꢂ CH3; t-Bu), 0.87 (3H, d, J 6.8, CHACHCHB), 0.86 (3H, d, J 6.8,
THF/water (3:1; 4 mL) gave after an acidic extraction, (ꢀ)-2-
phenylpropionic acid (R)-32 (13 mg, 58%) as
a colourless
oil;
½
a 2D0
ꢃ
¼ ꢀ71:8 (c 2.0, CHCl3) {lit.19
½
a 2D2
ꢃ
¼ ꢀ71:2 (c 0.66,
CHCl3)}, which was spectroscopically identical to that reported
previously.
For the hydrolysis of oxazolidin-2-one adduct (S,R)-syn-24 see
Ref. 19.
3
3
CHACHCHB) and 0.15 (6H, s, 2 ꢂ SiCH3); dC (100 MHz; CDCl3)
3
3

1548
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1536–1548
7. (a) Hintermann, T.; Seebach, D. Helv. Chem. Acta 1998, 81, 2093–2126; (b) Gaul,
Acknowledgements
C.; Schweizer, B. W.; Seiler, P.; Seebach, D. Helv. Chem. Acta 2002, 85, 1546–
1566.
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.
8. Delaunay, D.; Toupet, L.; Corre, M. L. J. Org. Chem. 1995, 60, 6604–6607.
9. Wu, Y.; Yang, Y.-Q.; Hu, Q. J. Org. Chem. 2004, 69, 3990–3992.
10. For 4-(4-hydroxyphenyl)-oxazolidin-2-one rac-13 a longer reaction time (12 h)
at an elevated temperature (rt) was required.
11. For related 5,5-dimethyl oxazolidin-2-ones see: 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. and references cited
therein.
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