Probing the parallel resolution of Mosher's acid using a combination of quasi-enantiomeric oxazolidin-2-ones

Article abstract of DOI:10.1016/j.tetasy.2008.04.032

Mosher's acid (2-methoxy-2-phenyl-2-trifluoromethylacetic acid) was resolved by parallel resolution of its corresponding pentafluorophenyl active ester using a quasi-enantiomeric combination of oxazolidin-2-ones.

Full text of DOI:10.1016/j.tetasy.2008.04.032

Tetrahedron: Asymmetry 19 (2008) 1274–1284
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Probing the parallel resolution of Mosher’s acid using a combination
of quasi-enantiomeric oxazolidin-2-ones
b
Sameer Chavda a, Elliot Coulbeck a, Marco Dingjan b, Jason Eames a, , Majid Motevalli
*
a Department of Chemistry, University of Hull, Cottingham Road, Kingston Upon Hull HU6 7RX, UK
b School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Mosher’s acid (2-methoxy-2-phenyl-2-trifluoromethylacetic acid) was resolved by parallel resolution
of its corresponding pentafluorophenyl active ester using a quasi-enantiomeric combination of oxazoli-
din-2-ones.
Received 18 April 2008
Accepted 28 April 2008
Available online 26 May 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
O
O
1. n-BuLi
The synthesis of enantiomerically pure carboxylic acids1 based
on the carbon-skeleton of phenylacetic acid, such as 2-phenylprop-
ionic acid 12 and Mandelic acid 2,3 are well documented (Scheme
1). Many of these derivatives have found widespread use as impor-
tant biological4 and synthetic intermediates.5
THF, -78 oC
HN
Ph
O
HN
O
Ph
CO2C6F5
2.
(2 equiv.)
i-Pr
H
CH3
rac-3
(R)-4
(S)-5
O
O
H
Me
CO2H
O
O
H
OH
CO2H
Ph
Me
Ph
Ph
Ph
N
O
N
O
2
1
H
H
Me
Ph
i-Pr
Scheme 1. 2-Phenylpropionic acid 1 and Mandelic acid 2.
(S,R)-syn-: (R,R)-anti-6
(R,S)-syn-: (S,S)-anti-7
88:12; 60%
95:5; 60%
2. Results and discussion
Scheme 2. Parallel kinetic resolution of active ester rac-3 using a quasi-enantio-
meric combination of oxazolidin-2-ones (R)-4 and (S)-5.
Over the last few years, we have been interested in the parallel
kinetic resolution6 of profen active esters,7,8 such as pentafluoro-
phenyl 2-phenylpropionate acid rac-3, using a combination of
quasi-enantiomeric Evans’ oxazolidin-2-ones (R)-4 and (S)-5 to
give the corresponding adducts (S,R)-syn-6 and (R,S)-syn-7 in high
yield and with excellent levels of diastereoselectivity (Scheme 2).
We have already demonstrated that efficient molecular recognition
and enantiomeric separation of active ester rac-3 [to give the sep-
arable and complementary adducts (S,R)-syn-6 and (R,S)-syn-7] can
be readily achieved using a quasi-enantiomeric combination of
oxazolidin-2-ones, (R)-4 and (S)-5, respectively (Scheme 2).7,9
Herein we report an extension to our methodology for the res-
olution of Mosher’s acid10 (2-methoxy-2-phenyl-2-trifluorometh-
ylacetic acid) rac-8 using a quasi-enantiomeric combination of
Evans’11 and Seebach’s oxazolidin-2-ones (R)-4 and (S)-9 (Scheme
3). We were interested in this particular12 combination of oxazoli-
din-2-ones due to their ease of separation. The active ester rac-10
O
O
Ph
CO2H
HN
Ph
O
HN
Ph
O
MeO CF3
Ph
Ph
(R)-4
(S)-9
rac-8
* Corresponding author. Tel.: +44 1482 466401; fax: +44 1482 466410.
E-mail address: j.eames@hull.ac.uk (J. Eames).
Scheme 3. Mosher’s acid rac-8, and quasi-enantiomeric oxazolidin-2-ones (R)-4
and (S)-9.
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.04.032

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1274–1284
1275
required for our study was synthesised in 88% yield by the addition
of DCC to a stirred solution of pentafluorophenol and Mosher’s acid
rac-8 in dichloromethane (Scheme 4 and Fig. 1).13
Ph
CO2C6F5
Ph
CO2H
C6F5OH, DCC
CH2Cl2
MeO CF3
MeO CF3
In order to get a measure of the potential enantiomeric recogni-
tion within our proposed parallel kinetic resolution, we first chose
to probe the mutual recognition between the racemic active ester
rac-10 and racemic Evans’ oxazolidin-2-one rac-4 (Scheme 5). The
addition of n-butyl lithium to a stirred solution of oxazolidin-2-one
rac-4 in THF at ꢀ78 °C, followed by the addition of active ester rac-
10, and stirring the resulting solution at room temperature for 2 h,
gave a separable mixture of diastereoisomeric adducts rac-syn- and
rac-anti-11 in 45% yield with good levels of diastereoisomeric con-
trol [ratio 79:21 (58% de)] (Scheme 5).15 The relative levels of enan-
tiomeric recognition and the overall levels of stereocontrol were
found to be similar to those obtained from 2-methoxy-2-phenyl-
acetic acid.16,17
(rac)-8
rac-10; 88%
Scheme 4. Synthesis of pentafluorophenyl 2-methoxy-2-phenyl-2-trifluoromethyl
acetate rac-10.
We next investigated the complementary kinetic resolution of
active ester rac-10 using enantiomerically pure oxazolidin-2-one
(R)-4 (Scheme 5). This kinetic chemical resolution proved to be
equally diastereoselective favouring the formation of oxazolidin-
2-one (S,R)-syn-11 [ratio (S,R)-syn-:(R,R)-anti-11: 80:20 (60% de)]
in 41% yield (Scheme 5). With this information in hand, we next
probed the complementary mutual and kinetic resolution of active
Figure 1. Molecular structure of pentafluorophenyl 2-methoxy-2-phenyl-2-trifluo-
romethyl acetate (R)-10, showing the atom labelling scheme. Displacement ellip-
soids are drawn at 50% probability level and the H atoms have been omitted.14
O
O
O
O
O
1. n-BuLi
THF, -78 oC
Ph
Ph
N
O
N
O
HN
Ph
O
Ph
CO2C6F5
F3C OMe
Ph
rac-anti-11
2.
MeO CF3
Ph
MeO CF3
rac-syn-11
79:21; 45%
rac-4
rac-10
3. 2 h, rt.
58% d.e.
O
O
O
N
O
O
1. n-BuLi
THF, -78 oC
Ph
Ph
O
N
O
HN
Ph
O
Ph
CO2C6F5
(2 equiv.)
2.
MeO CF3
Ph
(S,R)-syn-11
F3C OMe
Ph
MeO CF3
rac-10
80:20; 41%
60% d.e.
(R,R)-anti-11
(R)-4
3. 2 h, rt.
Scheme 5. Mutual and kinetic resolution of active ester rac-10 using oxazolidin-2-ones rac- and (R)-4.
O
O
O
O
O
1. n-BuLi
THF, -78 oC
Ph
Ph
N
O
N
O
HN
Ph
O
Ph
CO2C6F5
2.
MeO CF3
Ph
rac-anti-12
F3C OMe
Ph
Ph
Ph
Ph
Ph
Ph
Ph
MeO CF3
rac-9
rac-syn-12
67:33; 52%
34% d.e.
rac-10
3. 2 h, rt.
O
O
O
O
O
1. n-BuLi
THF, -78 oC
Ph
Ph
HN
Ph
O
N
O
N
O
Ph
CO2C6F5
2.
F3C OMe
Ph
MeO CF3
Ph
Ph
Ph
Ph
Ph
Ph
MeO CF3
Ph
rac-10
(S)-9
(R,S)-syn-12
(S,S)-anti-12
57:43; 51%
14% d.e.
(2 equiv.)
3. 2 h, rt.
Scheme 6. Mutual and kinetic resolution of active ester rac-10 using oxazolidin-2-ones rac- and (S)-9.

1276
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1274–1284
ester rac-10, using a more sterically-demanding oxazolidin-2-one,
namely 4,5,5-triphenyl-oxazolidin-2-ones rac- and (S)-9 (Scheme
6). These resolution processes proved to be slightly less stereo-
selective, favouring the formation of the oxazolidin-2-one adducts
rac-syn- and (R,S)-syn-12 with moderate levels of diastereoselec-
tivities (14–34% diastereoisomeric excess) (Scheme 6).15
from (S)-9], respectively (Scheme 7). The levels of diastereocontrol
were found to be similar to their complementary mutual kinetic
resolutions of active ester rac-10 involving oxazolidin-2-ones
rac-4 and rac-9, respectively, and the resulting oxazolidin-2-one
adducts were separated efficiently by column chromatography
(DRF = 0.32) (Schemes 5 and 6).
We first probed the parallel kinetic resolution of active ester
rac-10 using a quasi-enantiomeric combination of Evans’ oxazoli-
din-2-one (R)-4 and Seebach’s oxazolidin-2-one (S)-9 as we
believed this would be a mimic for the mutual kinetic resolution
of oxazolidin-2-one rac-4 as outlined in Scheme 5. Deprotonation
of a equimolar combination of oxazolidin-2-ones (R)-4 and (S)-9
using n-BuLi, followed by the addition of active ester rac-10, gave
a pair of separable diastereoisomeric oxazolidin-2-ones (S,R)-syn-
and (R,R)-anti-11 (ratio 80:20; 64% yield) [derived from (R)-4]
and (R,S)-syn- and (S,S)-anti-12 (ratio 62:38; 62% yield) [derived
In an attempt to improve the levels of diastereocontrol, we next
probed the parallel kinetic resolution of Evans’ oxazolidin-2-one
rac-4 using a quasi-enantiomeric mixture of active esters (R)-10
[derived from Mosher’s acid (R)-8] and (S)-13 [derived from (S)-
Ibuprofen]18 (Scheme 8). The addition of an equimolar amount of
active esters (R)-10 and (S)-13 to a stirred solution of the lithiated
oxazolidin-2-one [derived from the addition of n-butyl lithium to
oxazolidin-2-one rac-4], gave the corresponding diastereoisomeric
adducts (R,S)-syn-11 and (S,R)-syn-14 with high to moderate levels
of diastereoselectivity (58–64% de) (Scheme 8). The level of diaste-
O
O
O
O
Ph
Ph
N
O
N
O
MeO CF3
Ph
F3C OMe
Ph
O
O
1. n-BuLi
THF, -78oC
(R,R)-anti-11
(S,R)-syn-11
80:20; 64%
60% d.e.
HN
Ph
O
HN
Ph
O
2. (rac)-10
(2 equiv.)
Ph
O
O
O
O
Ph
3. 2 h, rt.
(S)-9
(R)-4
Ph
Ph
N
O
N
O
F3C OMe
Ph
MeO CF3
Ph
Ph
Ph
Ph
Ph
(S,S)-anti-12
(R,S)-syn-12
62:38; 62%
24% d.e.
Scheme 7. Parallel kinetic resolution of active ester rac-10 using a quasi-enantiomeric combination of oxazolidin-2-ones (R)-4 and (S)-9.
CO2C6F5
Ph
CO2C6F5
Me
H
F3C OMe
(S)-13
(R)-10
O
O
O
O
Ph
N
O
N
O
F3C OMe
Ph
(R,R)-anti-11
Me
H
Ph
O
(S,S)-anti-14
1. n-BuLi
THF, -78oC
HN
Ph
O
2. (R)-10 and
(S)-13
O
O
O
O
N
Ph
N
O
O
rac-4
F3C OMe
Ph
Me
H
Ph
(S,R)-syn-14 (major)
(R,S)-syn-11 (major)
syn-:anti-: 79:21; 62% (2 h, -78oC)
syn-:anti-: 79:21; 61% (2 h, rt)
syn-:anti-: 0% (2 h, -78oC)
syn-:anti-: 82:18; 42 % (2 h, rt)
Scheme 8. Sequential kinetic resolution of oxazolidin-2-one rac-4 using a quasi-enantiomeric combination of active esters (R)-10 and (S)-13.

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1274–1284
1277
reocontrol for (S,R)-syn-14 was comparable to that of its kinetic
resolution,19 whereas for (R,R)-anti-11, the diastereoselectivity
was significantly higher (Scheme 8). However, by quenching this
resolution after 2 h at ꢀ78 °C, only the less sterically-demanding
active ester (S)-13 [derived from (S)-Ibuprofen]18 appeared to have
reacted with the lithiated oxazolidin-2-one to give the correspond-
ing adduct (S,R)-syn-14 in a similar yield (62%) with comparable
diastereoselectivity (58% de) to that previously obtained (Scheme
8).20 This rate difference and the resulting increase in concentra-
tion of active ester (R)-10 appears to be sufficient21 enough to in-
crease the levels of diastereocontrol for the (R,S)-syn-11 through
a sequential (parallel) kinetic resolution (SPKR) (Scheme 8). These
resulting adducts 11 and 14 were efficiently separated by column
chromatography.
With these oxazolidin-2-one adducts (S,R)-syn-11 and (R,S)-syn-
12 in hand, we next investigated their hydrolysis using a combina-
tion of lithium hydroxide monohydrate and hydrogen peroxide in a
mixture of THF/H2O (3:1). Treatment of oxazolidin-2-ones (S,R)-
syn-11 and (R,S)-syn-12 with LiOH/H2O2 in THF/H2O (3:1) at rt
for 12 h, gave the corresponding Mosher’s acids (S)- and (R)-8 in
6% and 46% yields, respectively (Scheme 9). The resulting oxazoli-
din-2-ones (R)-4 and (S)-9 were recovered in related 5% and 17%
yields,22 respectively (Scheme 9). The overall yield for these seem-
ingly simple hydrolyses were low due to competitive endo-cleav-
age of the oxazolidin-2-one adducts (S,R)-syn-11 and (R,S)-syn-12
to give the corresponding amides (S,R)-15 and (R,S)-16 in 80%
and 24% yields (Scheme 9). This type of endo-cleavage23 is unsur-
prising for sterically-demanding oxazolidin-2-one adducts, such
as (S,R)-syn-11, where exo-cleavage is evidently disfavoured due
to steric hindrance [(S,R)-15:(R)-4 ratio 92:8—determined by
400 MHz 1H NMR spectroscopy]. For C(5)-disubstituted oxazoli-
din-2-ones, such as Seebach’s oxazolidin-2-one 9, which were de-
signed to disfavour this type of endo-cleavage pathway,12,23,24 do
favour the required exo-cleavage pathway [(R,S)-16:(S)-9 ratio
33:67—determined by 400 MHz 1H NMR spectroscopy] to give
the Mosher’s acid (R)-8 in 46% yield (Scheme 9).
Further evidence for this unusual endo-cleavage pathway can be
seen from the formation of two by-products, amides (S,R)-syn-17
(formed in 9–15%) and (S,R)-syn-18 (formed in 5–13%), derived
from the addition of lithium butoxide [a contaminant present in
varying amounts in n-BuLi (in hexane) due to reaction with molec-
ular O2] to the corresponding oxazolidin-2-one adducts (S,R)-syn-
11 and (S,R)-syn-12 (Scheme 10). The amount of amides 17 and
18 formed were found to be dependent on the quality of the n-
BuLi/hexane solution, THF25 used and the reaction time. These
amide adducts [e.g., (R,S)-syn-18] can be synthesised in moderate
yield (23%) by addition of LiOBu (formed by addition of n-BuLi to
BuOH in THF) to a stirred solution oxazolidin-2-one (R,S)-syn-12
in THF at ꢀ78 °C (Scheme 11). However, the addition of an excess
amount of lithium butoxide (2 equiv) to (S,R)-syn-11 and (R,S)-syn-
O
O
O
O
Ph
Ph
NH
O
OBu
NH
O
OBu
MeO CF3
Ph
F3C OMe
Ph
Ph
Ph
(R,S)-18
(S,R)-17
Scheme 10. Formation of amides (S,R)-syn-17 and (R,S)-syn-18 by in situ endo-
cleavage of (S,R)-syn-11 and (R,S)-syn-12.
O
O
Ph
OH
O
HN
Ph
(R)-4; 5%
O
O
O
MeO CF3
(S)-8; 6%
Ph
Ph
LiOH, H2O2
N
O
THF, H2O (3:1)
MeO CF3
Ph
(S,R)-syn-11
NH
OH
MeO CF3
Ph
(S,R)-15; 80%
O
O
Ph
OH
HN
Ph
O
O
O
F3C OMe
Ph
LiOH, H2O2
THF, H2O (3:1)
Ph
Ph
N
O
(R)-8; 46%
(S)-9; 17%
F3C OMe
Ph
(R,S)-syn-12
Ph
Ph
O
Ph
NH
OH
Ph
F3C OMe
Ph
Ph
(S,R)-16; 24%
Scheme 9. Exo- and endo-cleavage of oxazolidin-2-one adducts (S,R)-syn-11 and (R,S)-syn-12.

1278
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1274–1284
O
O
Ph
OBu
HN
Ph
O
F3C OMe
Ph
Ph
O
O
n-BuLi (1 equiv.)
BuOH (1 equiv.)
(R)-10; 16%
(S)-9; 18%
Ph
N
O
THF
O
O
O
F3C OMe
Ph
(R,S)-syn-12
Ph
Ph
Ph
Ph
NH
OH
Ph
NH
O
OBu
F3C OMe
F3C OMe
Ph
Ph
Ph
Ph
Ph
(R,S)-syn-16; 3%
(R,S)-syn-18; 23%
(R,S)-syn-12: (R)-10:(R,S)-syn-16:(R,S)-syn-18 = 34:38:3:25
Scheme 11. Formation of amides (R,S)-syn-16 and (R,S)-syn-18 by in situ endo-cleavage of (R,S)-syn-12.
O
O
O
n-BuLi (3 equiv.)
BuOH (5 equiv.)
Ph
Ph
OH
N
O
NH
THF
MeO CF3
Ph
(S,R)-syn-11
MeO CF3
Ph
(S,R)-syn-15; 42%
O
O
O
O
O
n-BuLi (3 equiv.)
BuOH (5 equiv.)
Ph
F3C
Ph
Ph
OH
Ph
N
O
NH
NH
O
OBu
THF
OMe
OMe
Ph
(R,S)-syn-16; 3%
F3C OMe
Ph
F3C
Ph
Ph
Ph
(R,S)-syn-12
Ph
Ph
Ph
(R,S)-syn-18; 27%
(R,S)-syn-12: (R)-10:(R,S)-syn-16:(R,S)-syn-18 = 5:52:8:35
Scheme 12. Formation of amides (S,R)-syn-15 and (R,S)-syn-18 by in situ endo-cleavage of (S,R)-syn-11 and (R,S)-syn-12.
12 gave the corresponding amides (S,R)-syn-15 and (R,S)-syn-16 in
42% and 3%, respectively, through butoxycarbonyl cleavage of the
intermediate carbonates (S,R)-syn-17 and (R,S)-syn-18, respectively
(Scheme 12). Interestingly, for (R,S)-syn-12 using an excess of
n-BuLi (3 equiv), the relative amount of exo- and endo-cleavage
remained unchanged [ratio—53:47 (1 equiv of n-BuOLi) and
55:45 (3 equiv of n-BuOLi), respectively], whereas, the relative pro-
portion of (R,S)-syn-16 increased [from 11:89 to 23:77 for (R,S)-
syn-16:(R,S)-syn-18] through competitive butoxycarbonyl cleavage
of (R,S)-syn-18 to give (R,S)-syn-16 and dibutylcarbonate.26
Whereas, for the less sterically-demanding oxazolidin-2-one
(S,R)-syn-11, exclusive endo-cleavage was preferred to give the
amide (S,R)-syn-15 in 42% yield via a double n-BuOLi addition
process (Scheme 12).
4. Experimental
4.1. General
All solvents were distilled before use. All reactions were carried
out under nitrogen using oven-dried glassware. Flash column chro-
matography 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 deute-
rium lock. Chemical shifts are quoted in parts per million down-
field from tetramethylsilane. Carbon NMR spectra were recorded
with broad proton decoupling. Infrared spectra were recorded on
a Shimadzu 8300 FTIR spectrometer. Optical rotation was mea-
sured using an automatic AA-10 Optical Activity Ltd polarimeter.
3. Conclusion
4.1.1. Pentafluorophenyl 1-trifluoromethyl-1-methoxy-
phenylacetate (R)-10
In conclusion, we have demonstrated the parallel resolution of
Mosher’s acid rac-8 using a combination of quasi-enantiomeric
oxazolidin-2-ones as mutual resolving components. The overall
levels of diastereoselectivity were shown to be good (up to 60%
de). This level of mutual recognition could be increased to 64%
de via the use of differentially selective surrogate active esters,
such as (S)-3 or (S)-13, using a sequential parallel kinetic resolution
approach. Hydrolysis of the resulting adducts leads to competitive
endo- and exo-cleavage pathways.
N,N0-Dicyclohexylcarbodiimide (DCC) (1.75 g, 8.49 mmol) was
slowly added to a stirred solution of 1-trifluoromethyl-1-meth-
oxy-phenylacetic acid (R)-8 (1.80 g, 7.71 mmol) in dichlorometh-
ane (10 ml) at room temperature. The resulting solution was
stirred for 15 min.
A solution of pentafluorophenol (1.41 g,
7.71 mmol) in dichloromethane (3 ml) was slowly added and the
resulting solution was stirred for a further 2 h. The resulting white

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1274–1284
1279
precipitate (dicyclohexylurea) was removed through filtration
(using a sintered funnel). The reaction was quenched with water
(20 ml) and extracted with dichloromethane (3 ꢁ 10 ml). The com-
bined organic layers were dried over MgSO4 and evaporated under
reduced pressure. The residue was purified by flash column chro-
matography on silica gel eluting with light petroleum ether (bp
40–60 °C)/diethyl ether (9:1) to give the pentafluorophenyl 1-tri-
fluoromethyl-1-methoxy-phenylacetate (R)-10 (2.86 g, 92%) as
needle-like crystals; RF [light petroleum ether (bp 40–60 °C)/
diethyl ether (9:1)] 0.78; mp 43–44 °C (lit.27 45 °C); mmax(CH2Cl2)
cmꢀ1 3056, 2999, 2938 and 2854 (C–H aromatic), 1790 (C@O),
bined 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 (1:1) to give a separable diastereoiso-
meric mixture (syn-:anti- 79:21) of oxazolidin-2-one rac-syn-11
(0.17 g, 36 %) as plate-like crystals; RF [light petroleum ether (bp
40–60 °C)/diethyl ether (1:1)] 0.35; mp 158–160 °C; mmax(CH2Cl2)
cmꢀ1 1796 (C@O), 1702 (C@O) and 1262 (C–F); dH (400 MHz,
CDCl3) 7.46–7.41 (2H, m, 2 ꢁ CH; Ph), 7.37–7.27 (8H, m, 8 ꢁ CH;
Ph), 5.56 (1H, dd, J 6.0 and 2.5, PhCHN), 4.60 (1H, t, J 6.0, CHAHBO),
4.26 (1H, dd, J 6.0 and 2.5, CHAHBO) and 3.52 (3H, s, CH3O); dC
(100 MHz, CDCl3) 166.6 (NC@O), 150.1 (OC@O), 138.6 (i-C; Ph),
132.2 (i-C; Ph), 129.7,1 129.6,3 129.5,1 128.4,2 127.11 and 127.02
22
and 1266 and 1176 (C–F); ½aꢂD ¼ þ42:4 (c 1.02, CHCl3) [lit.27
22
+43.5] {for (S)-10 ½aꢂD ¼ ꢀ47:1 (c 1.22, CHCl3)}; dH (400 MHz,
1
2
CDCl3) 7.62–7.60 (2H, m, 2 ꢁ CH; Ph), 7.49–7.45 (3H, m, 3 ꢁ CH;
Ph) and 3.69 (3H, s, CH3O); dC (100 MHz, CDCl3) 163.2 (C@O),
(10 ꢁ CH; 2 ꢁ Ph), 123.6 (1C, q, JCF 291.2, CF3), 86.2 (1C, q, JCF
4
25.9, PhCCF3), 70.4 (CH2O), 59.1 (PhCHN) and 56.5 (1C, d, JCF 1.9,
1
2
þ
140.9 (142.25 and 139.73, 2C, ddt, JC,F = 253.1 Hz, JC,F = 12.0 Hz
CH3O); dF (378 MHz, CDCl3) ꢀ71.0 (1C, s, CF3) (Found MNH4
3
and JC,F = 4.6 Hz, C(2)–F), 140.1 (141.37 and 138.83, 1C, dtt,
397.1372. C19H20F3N2O4 requires MNH4þ, 379.1370); and the oxaz-
olidin-2-one rac-anti-11 (43 mg, 9 %) as a pale yellow oil; RF [light
petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.13; mmax
(CH2Cl2)/cmꢀ1 1803 (C@O), 1702 (C@O) and 1256 (C–F); dH
(400 MHz, CDCl3) 7.34–7.13 (10H, m, 2 ꢁ CH; 2 ꢁ Ph), 5.25 (1H,
dd, J 8.0 and 2.0, PhCHN), 4.43 (1H, dd, J 8.8 and 8.0, CHAHBO),
4.08 (1H, dd, J 8.8 and 2.0, CHAHBO) and 3.42 (3H, s, CH3O); dC
(100 MHz, CDCl3) 165.2 (NC@O), 149.9 (OC@O), 138.5 (i-C; Ph),
132.0 (i-C; Ph), 129.4,1 129.1,3 129.0,1 128.0,2 126.61 and 126.02
2
3
1JC,F = 254.0 Hz, JC,F = 13.8 Hz and JC,F = 3.8 Hz, C(4)–F), 138.0
1
2
(139.24 and 136.89, 2C, dtdd, JC,F = 249.0 Hz, JC,F = 12.9 Hz,
3JC,F = 5.3 and JC,F = 3.0 Hz, C(3)–F), 130.9 (i-C; Ph), 130.3,2
4
128.7,2 127.21 (5 ꢁ CH; Ph), 124.2 (1C, tdt, JC,F = 14.2 Hz,
2
4JC,F = 4.6 Hz and JC,F = 2.3 Hz, i-CO; OC6F5), 122.9 (1C, q, JCF
3
1
2
288.2, CF3), 85.4 (1C, q, JCF 28.4, PhCCF3) and 56.5 (CH3O); dF
3
(378 MHz, CDCl3) ꢀ71.8 (1C, s, CF3), ꢀ151.4 (2C, d, JCF 18.5,
3
o-CF; C6F5), ꢀ155.8 (1C, d, JCF 18.5, p-CF; C6F5) and ꢀ161.1 (2C,
d, JCF 18.5, m-CF; C6F5); m/z 189.1 (100%, PhC+(CF3)OMe).
(10 ꢁ CH; 2 ꢁ Ph), 123.2 (1C, q, JCF 290.4, CF3), 85.7 (1C, q, JCF
3
1
2
4
26.1, PhCCF3), 70.0 (CH2O), 58.8 (PhCHN) and 56.1 (1C, d, JCF 2.3,
þ
4.1.2. Pentafluorophenyl 1-trifluoromethyl-1-methoxy-
phenylacetate rac-10
CH3O); dF (378 MHz, CDCl3) ꢀ70.7 (1C, s, CF3) (Found MNH4
397.1370. C19H20F3N2O4 requires MNH4þ, 397.1370).
In the same way as above, N,N0-dicyclohexylcarbodiimide (DCC)
(0.71 g, 3.44 mmol), 1-trifluoromethyl-1-methoxy-phenylacetic
acid (R)-8 (0.74 g, 3.16 mmol) and pentafluorophenol (0.58 g,
3.16 mmol) in dichloromethane (10 ml) gave after purification by
column chromatography on silica gel eluting with light petroleum
ether (bp 40–60 °C)/diethyl ether (9:1) pentafluorophenyl 1-tri-
fluoromethyl-1-methoxy-phenylacetate rac-10 (1.11 g, 88%) as
needle-like crystals; RF [light petroleum ether (bp 40–60 °C)/
diethyl ether (9:1)] 0.87; mp 80–82 °C; mmax (CH2Cl2) cmꢀ1 3057
and 2854 (C–H aromatic), 1790 (C@O), and 1266 and 1176 (C–F);
dH (400 MHz, CDCl3) 7.65–7.59 (2H, m, 2 ꢁ CH; Ph), 7.50–7.43
(3H, m, 3 ꢁ CH; Ph) and 3.70 (3H, s, CH3O); dC (100 MHz, CDCl3)
4.1.4. Kinetic resolution of active ester rac-10 using oxazolidin-
2-one (R)-4; synthesis of (S,R)-4-phenyl-3-(2-methoxy-2-
phenyl-2-trifluoromethyl-acetyl)-oxazolidin-2-one syn-11
In the same way as above, n-butyl lithium (0.35 ml, 2.5 M in
hexane, 0.88 mmol), oxazolidin-2-one (R)-4 (0.12 g, 0.74 mmol)
and active ester rac-10 (0.59 g, 1.47 mmol) gave a crude mixture
of oxazolidin-2-ones (S,R)-syn- and (R,R)-anti-11 (ratio 79:21). This
residue was purified by column chromatography on silica gel elut-
ing with light petroleum ether (bp 40–60 °C)/diethyl ether (9:1) to
give the oxazolidin-2-one (S,R)-syn-11 (38 mg, 33%) as a white
crystalline solid; RF [light petroleum ether (bp 40–60 °C)/diethyl
ether (1:1)] 0.35; mp 173–175 °C; mmax(CH2Cl2) cmꢀ1 1796
1
163.3 (C@O), 140.9 (142.20 and 139.67, 2C, ddt, JC,F = 253.1 Hz,
22
3
2JC,F = 12.0 Hz and JC,F = 4.6 Hz, C(2)–F), 140.0 (141.32 and
(C@O), 1702 (C@O) and 1262 (C–F); ½aꢂD ¼ ꢀ17:4 (c 1.4, CHCl3);
1
2
3
138.78, 1C, dtt, JC,F = 254.0 Hz, JC,F = 13.8 Hz and JC,F = 3.8 Hz,
dH (400 MHz, CDCl3) 7.45–7.42 (2H, m, 2 ꢁ CH; Ph), 7.35–7.26
(8H, m, 8 ꢁ CH; 2 ꢁ Ph), 5.50 (1H, dd, J 6.0 and 2.5, PhCHN), 4.55
(1H, t, J 6.0, CHAHBO), 4.22 (1H, dd, J 6.0 and 2.5, CHAHBO) and
3.45 (3H, s, CH3O); dC (100 MHz, CDCl3) 166.3 (NC@O), 149.7
(OC@O), 138.1 (i-CC; Ph), 131.8 (i-C; Ph), 129.3,1 129.2,3 129.0,1
1
C(4)–F), 137.9 (139.19 and 136.70, 2C, dtdd, JC,F = 249.0 Hz,
2JC,F = 12.9 Hz, JC,F = 5.3 and JC,F = 3.0 Hz, C(3)–F), 130.9 (i-C; Ph),
3
4
130.2,2 128.6,2 127.11 (5 ꢁ CH; Ph), 124.1 (1C, tdt, JC,F = 14.2 Hz,
2
4JC,F = 4.6 Hz and JC,F = 2.3 Hz, i-CO; OC6F5), 122.8 (1C, q, JCF
3
1
2
1
288.2, CF3), 85.3 (1C, q, JCF 28.4, PhCCF3) and 56.4 (CH3O); dF
127.6,2 126.61 and 126.52 (10 ꢁ CH; 2 ꢁ Ph), 123.3 (1C, q, JCF
3
2
(378 MHz, CDCl3) ꢀ71.8 (1C, s, CF3), ꢀ151.4 (2C, d, JCF 18.5,
291.3, CF3), 85.6 (1C, q, JCF 26.2, PhCCF3), 69.9 (CH2O), 58.7
3
4
o-CF; C6F5), ꢀ155.9 (1C, d, JCF 18.5, p-CF; C6F5) and ꢀ161.3 (2C,
(PhCHN) and 56.0 (1C, d, JCF 2.3, CH3O); dF (378 MHz, CDCl3)
d, JCF 18.5, m-CF; C6F5); m/z 189.1 (100%, PhC+(CF3)OMe).
ꢀ71.0 (1C, s, CF3) (Found MNH4 397.1372. C19H20F3N2O4 requires
3
þ
MNH4þ, 379.1370); and the oxazolidin-2-one (R,R)-anti-11 (9 mg,
8%) as white crystalline solid; RF [light petroleum ether (bp 40–
60 °C)/diethyl ether (1:1)] 0.13; mp 86–88 °C; mmax (CH2Cl2) cmꢀ1
4.1.3. (SR,RS)-4-Phenyl-3-(2-methoxy-2-phenyl-2-
trifluoromethyl-acetyl)-oxazolidin-2-one rac-syn-11 and
(RS,RS)-4-phenyl-3-(2-methoxy-2-phenyl-2-trifluoromethyl-
acetyl)-oxazolidin-2-one rac-anti-11—mutual kinetic
22
1803 (C@O), 1702 (C@O) and 1256 (C–F); ½aꢂD ¼ þ136:4 (c 1.07,
CHCl3); dH (400 MHz, CDCl3) 7.34–7.13 (10H, m, 2 ꢁ CH; 2 ꢁ Ph),
5.25 (1H, dd, J 7.8 and 2.0, PhCHN), 4.43 (1H, dd, J 8.8 and 8.0,
CHAHBO), 4.08 (1H, dd, J 8.8 and 2.0, CHAHBO), 3.42 (3H, s, CH3O);
dC (100 MHz, CDCl3) 165.2 (NC@O), 149.9 (OC@O), 138.5
(i-CC; Ph), 132.0 (i-CC; Ph), 129.4,1 129.1,3 129.0,1 128.0,2 126.61
resolution of active ester rac-10 using oxazolidin-2-one rac-4
n-BuLi (0.60 ml, 2.5 M in hexane, 1.50 mmol) was added to a
stirred solution of oxazolidin-2-one rac-4 (0.205 g, 1.26 mmol) in
THF (50 ml) at ꢀ78 °C. After stirring for 1 h, a solution of active es-
ter rac-10 (0.61 g, 1.52 mmol) in THF (10 ml) was slowly added.
The resulting solution was stirred for 2 h at ꢀ78 °C and then al-
lowed to warm up to room temperature. The resulting solution
was stirred for a further 2 h. The reaction was quenched with water
(10 ml) and extracted with diethyl ether (2 ꢁ 20 ml). The com-
1
and 126.02 (10 ꢁ CH; 2 ꢁ Ph), 123.2 (1C, q, JCF 290.4, CF3), 85.7
2
(1C, q, JCF 26.1, PhCCF3), 70.0 (CH2O), 58.8 (PhCHN) and 56.1
4
(1C, d, JCF 2.3, CH3O); dF (378 MHz, CDCl3) ꢀ70.7 (1C, s, CF3)
þ
þ
(Found MNH4
397.1370).
397.1370. C19H20F3N2O4 requires MNH4 ,

1280
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1274–1284
4.1.5. Mutual kinetic resolution of active ester rac-10 using
oxazolidin-2-one rac-9; synthesis of (SR,RS)-4-phenyl-5,5-
diphenyl-3-(2-methoxy-2-phenyl-2-trifluoromethyl-acetyl)-
oxazolidin-2-one rac-syn-12 and (RS,RS)-4-phenyl-5,5-
diphenyl-3-(2-methoxy-2-phenyl-2-trifluoromethyl-acetyl)-
oxazolidin-2-one rac-anti-12
Characterisation data for oxazolidin-2-one (R,S)-syn-12;
25
½aꢂD ¼ ꢀ2:7 (c 0.9, CHCl3)}; RF [light petroleum ether (bp 40–
60 °C)/diethyl ether (1:1)] 0.77; mmax (CH2Cl2) cmꢀ1 1792 (C@O),
1715 (C@O) and 1267 (C–F); dH (400 MHz, CDCl3) 7.53–7.47 (2H,
m, 2 ꢁ CH; Ph), 7.40–7.30 (4H, m, 4 ꢁ CH, 2 ꢁ Ph), 7.10 (1H, t, J
7.3, CH; Ph), 7.05–6.85 (13H, m, 13 ꢁ CH; 4 ꢁ Ph), 6.23 (1H, s,
PhCHN) and 3.35 (3H, s, CH3O); dC (100 MHz, CDCl3) 165.6 (NC@O),
149.0 (OC@O), 141.7, 137.2, 135.1 and 131.4 (4 ꢁ i-C; Ph), 129.0,2
128.9,1 128.8,1 128.4,1 128.3,2 127.8,2 127.7,2 127.6,2 127.5,2
In the same way as above, n-butyl lithium (0.25 ml, 2.5 M in
hexane, 0.63 mmol), oxazolidin-2-one rac-9 (0.17 g, 0.54 mmol)
and active ester rac-10 (0.25 g, 0.62 mmol) gave a crude mixture
of oxazolidin-2-ones rac-syn-and rac-anti-12 (ratio 67:33). This
residue was purified by flash column chromatography eluting with
light petroleum ether (bp 40–60 °C)/diethyl ether (1:1) to give an
inseparable mixture (ratio 67:33) of oxazolidin-2-ones rac-syn-
and rac-anti-12 (149 mg, 52%) as a white solid; mp 182–185 °C.
Characterisation data for [light petroleum ether (bp 40–60 °C)/
diethyl ether (1:1)] 0.77; mmax(CH2Cl2) cmꢀ1 1792 (C@O), 1715
(C@O) and 1267 (C–F); dH (400 MHz, CDCl3) 7.53–7.47 (2H, m,
2 ꢁ CH; Ph), 7.40–7.30 (4H, m, 4 ꢁ CH, 2 ꢁ Ph), 7.10 (1H, t, J 7.3,
CH; Ph), 7.05–6.85 (13H, m, 13 ꢁ CH; 4 ꢁ Ph), 6.23 (1H, s, PhCHN)
and 3.35 (3H, s, CH3O); dC (100 MHz, CDCl3) 165.6 (NC@O), 149.0
(OC@O), 141.7, 137.2, 135.1 and 131.4 (4 ꢁ i-C; Ph), 129.0,2
128.9,1 128.8,1 128.4,1 128.3,2 127.8,2 127.7,2 127.6,2 127.5,2
1
126.4,1 125.92 and 125.52 (20 ꢁ CH; 4 ꢁ Ph), 123.3 (1C, q, JCF
2
290.4, CF3), 89.2 (C(Ph)2O), 85.4 (1C, JCF 25.4, PhC), 67.6 (PhCHN)
4
and 56.0 (1C, d, JCF 2.3, CH3O); dF (378 MHz, CDCl3) ꢀ71.7 (1C, s,
CF3) (Found MNa+ 554.1548. C31H24F3NO4Na requires MNa+,
25
554.1550); and oxazolidin-2-one (S,S)-anti-12; ½aꢂD ¼ ꢀ232:4 (c
1.05, CHCl3); RF [light petroleum ether (bp 40–60 °C)/diethyl ether
(1:1)] 0.77; mmax(CH2Cl2) cmꢀ1 1807 (C@O), 1702 (C@O) and 1256
(C–F); dH (400 MHz, CDCl3) 7.52 (2H, d, J 7.4, 2 ꢁ CH; Ph), 7.35–
7.18 (8H, m, 8 ꢁ CH, 3 ꢁ Ph), 7.09–7.05 (3H, m, 4 ꢁ CH, Ph), 6.95
(7H, m, 7 ꢁ CH; 3 ꢁ Ph), 6.00 (1H, s, PhCHN) and 2.92 (3H, s,
CH3O); dC (100 MHz, CDCl3) 165.3 (NC@O), 149.0 (OC@O), 141.2,
136.9, 134.8 and 132.1 (4 ꢁ i-C; Ph), 129.3,1 129.0,2 128.8,1
128.5,1 128.3,2 128.0,2 127.7,2 127.6,1 127.4,2 126.5,2 125.82 and
126.4,1 125.92 and 125.52 (20 ꢁ CH; 4 ꢁ Ph), 123.3 (1C, q, JCF
125.52 (20 ꢁ CH; 4 ꢁ Ph), 123.1 (1C, q, JCF 290.5, CF3), 89.1
1
1
2
2
290.4, CF3), 89.2 (C(Ph)2O), 85.4 (1C, JCF 25.4, PhC), 67.6 (PhCHN)
(C(Ph)2O), 85.6 (1C, JCF 25.4, PhC), 67.7 (PhCHN) and 55.3 (1C, d,
4
and 56.0 (1C, d, JCF 2.3, CH3O); dF (378 MHz, CDCl3) ꢀ71.7 (1C, s,
4JCF 2.3, CH3O); dF (378 MHz, CDCl3) ꢀ70.3 (1C, s, CF3) (Found
CF3) (Found MNa+ 554.1548. C31H24F3NO4Na requires MNa+,
554.1550).
MH+ 532.1732. C31H25F3NO4 requires MH+, 532.1732).
rac-anti-12; RF [light petroleum ether (bp 40–60 °C)/diethyl
ether (1:1)] 0.77; mmax (CH2Cl2) cmꢀ1 1807 (C@O), 1702 (C@O)
and 1256 (C–F); dH (400 MHz, CDCl3) 7.52 (2H, d, J 7.4, 2 ꢁ CH;
Ph), 7.35–7.18 (8H, m, 8 ꢁ CH, 3 ꢁ Ph), 7.09–7.05 (3H, m, 3 ꢁ CH,
Ph), 6.95 (7H, m, 7 ꢁ CH; 3 ꢁ Ph), 6.00 (1H, s, PhCHN) and 2.92
(3H, s, CH3O); dC (100 MHz, CDCl3) 165.3 (NC@O), 149.0 (OC@O),
141.2, 136.9, 134.8 and 132.1 (4 ꢁ i-C; Ph), 129.3,1 129.0,2 128.8,1
128.5,1 128.3,2 128.0,2 127.7,2 127.6,1 127.4,2 126.5,2 125.82 and
4.1.7. Parallel kinetic resolution of racemic active ester rac-10
using a combination of quasi-enantiomeric combination of
oxazolidin-2-ones (R)-4 and (S)-9
In the same way as above, n-butyl lithium (0.44 ml, 2.5 M in
hexane, 1.10 mmol), oxazolidin-2-one (R)-4 (75 mg, 0.46 mmol),
oxazolidin-2-one (S)-9 (0.148 g, 0.47 mmol) and active ester rac-
10 (0.44 g, 1.10 mmol) gave a crude mixture of oxazolidin-2-ones
(R,R)-anti- and (S,R)-syn-11 (ratio: 20:80; 64%) and (S,S)-anti- and
(R,S)-syn-12 (ratio: 38:62; 62%). This residue was purified by flash
column chromatography eluting with light petroleum ether (bp
40–60 °C)/diethyl ether (8:2) to give an inseparable mixture of
oxazolidin-2-ones (R,R)-anti- and (S,R)-syn-11 (0.11 g, 64%) {RF
[light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] = 0.13
and 0.35, respectively}, and (S,S)-anti- and (R,S)-syn-12 (0.15 g,
62%) {RF [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)]
1
125.52 (20 ꢁ CH; 4 x Ph), 123.1 (1C, q, JCF 290.5, CF3), 89.1
2
(C(Ph)2O), 85.6 (1C, JCF 25.4, PhC), 67.7 (PhCHN) and 55.3 (1C, d,
4JCF 2.3, CH3O); dF (378 MHz, CDCl3) ꢀ70.3 (1C, s, CF3) (Found
MH+ 532.1732. C31H25F3NO4 requires MH+, 532.1732).
4.1.6. Kinetic resolution of active ester (S)-10 using oxazolidin-
2-one (S)-9; synthesis of (R,S)-4-phenyl-5,5-diphenyl-3-(2-
methoxy-2-phenyl-2-trifluoromethyl-acetyl)-oxazolidin-2-one
syn-12
25
= 0.77} {for (S,S)-anti-12; ½aꢂD ¼ ꢀ232:4 (c 1.05, CHCl3) and (R,S)-
25
syn-12; ½aꢂD ¼ ꢀ2:7 (c 0.9, CHCl3)}. These adducts were spectro-
scopically identical to those previously obtained.
In the same way as above, n-butyl lithium (0.10 ml, 2.5 M in
hexane, 0.24 mmol), oxazolidin-2-one (S)-9 (68 g, 0.22 mmol) and
active ester rac-10 (0.17 g, 0.43 mmol) gave a crude mixture of
oxazolidin-2-ones (R,S)-syn-12 and (S,S)-anti-12 (ratio 57:43). This
residue was purified by flash column chromatography eluting with
light petroleum ether (bp 40–60 °C)/diethyl ether (1:1) to give
racemic butyl 2-phenyl-2-methoxy-2-trifluoromethyl acetate
(23 mg, 18 %) as a colourless oil; RF [light petroleum ether (bp
40–60 °C)/diethyl ether (1:1)] 0.87; mmax(CH2Cl2) cmꢀ1 1747
(C@O); dH (400 MHz, CDCl3) 7.51–7.45 (2H, m, 2 ꢁ CH; PhS),
7.53–7.48 (2H, m, 2 ꢁ CH; Ph), 7.41–7.36 (3H, m, 3 ꢁ CH; Ph),
4.1.8. Parallel kinetic resolution of oxazolidin-2-one rac-4
using a combination of quasi-enantiomeric active esters (R)-10
and (S)-13 for 2 h at ꢀ78 °C
In the same way as above, n-butyl lithium (0.43 ml, 2.5 M in
hexane, 1.08 mmol), oxazolidin-2-one rac-4 (0.145 g, 0.89 mmol),
active ester (S)-13 (0.20 g, 0.54 mmol) and active ester (R)-10
(0.216 g, 0.54 mmol) for 2 h at ꢀ78 °C gave a crude mixture of
Evans’ oxazolidin-2-ones (S,S)-anti- and (S,R)-syn-14 (ratio:
21:79). This residue was purified by flash column chromatography
eluting with light petroleum ether (bp 40–60 °C)/diethyl ether
(7:3) to give the oxazolidin-2-one profen adducts (S,R)-syn- and
(S,S)-anti-14 (ratio 79:21; 0.192 g, 62% yield).
4
4.36–4.25 (2H, m, CH2O), 3.53 (3H, q, JCF 1.1, OCH3), 1.70–1.62
(2H, m, CH2), 1.39–1.30 (2H, appears as a br sextet, J 7.3, CH2)
and 0.89 (3H, t, J 7.5, CH3CH2); dC (100 MHz, CDCl3) 166.5 (C@O),
132.3 (i-C; Ph), 129.5,1 128.32 and 127.22 (5 ꢁ CH; Ph), 124.1 (1C,
Characterisation data for oxazolidin-2-one (S,S)-anti-14; white
solid; mp 155–158 °C; RF [light petroleum ether (bp 40–60 °C)/
1
2
25
q, JCF 286.5, CF3), 84.5 (1C, q, JCF 26.7, PhCCF3), 66.2 (CH2O),
55.3 (OCH3), 30.3 (CH2), 18.9 (CH2) and 13.4 (CH3); dF (378 MHz,
CDCl3) ꢀ71.5 (1C, s, CF3) (Found MNH4þ 308.1467. C14H21F3NO3 re-
quires MNH4þ, 308.1468); and an inseparable diastereoisomeric
mixture (syn-:anti-: 57:43) of oxazolidin-2-ones, (R,S)-syn- and
(S,S)-anti-12 (59 mg, 51%) as a colourless oil.
diethyl ether (1:1)] 0.62; ½aꢂD ¼ þ156:0 (c 3.5, CHCl3) {for (R,R)-
25
anti-14; ½aꢂD ¼ ꢀ151:3 (c 1.3, CHCl3)}; mmax(CHCl3) cmꢀ1 1780
(C@O), 1701 (C@O), and 1513 (Ar); dH (400 MHz; CDCl3) 7.39–
7.23 (7H, m, 7 ꢁ CH; Ar and Ph), 7.07 (2H, d, J 8.2, 2 ꢁ CH, Ar),
5.33 (1H, dd, J 8.9 and 3.2, PhCHN), 5.10 (1H, q, J 7.1, ArCHCH3),
4.55 (1H, t, J 8.9, CHAHBO), 4.20 (1H, dd J 8.9 and 3.2, CHAHBO),

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1274–1284
1281
þ
2.42 (2H, d, J 7.2, CH2Ar), 1.88–1.78 (1H, nonet, J 6.8, CH(CH3)2),
1.39 (3H, d, J 7.1, ArCHCH3) and 0.89 (6H, d, J 6.7, 2 ꢁ CH3;
CHACHCHB); dC (100.6 MHz; CDCl3) 173.9 (NC@O), 153.2 (OC@O),
ꢀ70.7 (1C, s, CF3) (Found MNH4 397.1370. C19H20F3N2O4 requires
MNH4þ, 379.1370).
3
3
140.6 (i-C; Ar), 138.3 (i-C; Ar), 137.0 (i-C; Ph), 129.3 and 128.0
(2 ꢁ CH; Ar), 128.8,2 128.51 and 125.82 (5 ꢁ CH; Ph), 69.6 (CH2O),
57.8 (PhCHN), 45.1 (CH(CH3)2), 43.3 (ArCHCH3), 30.2 (CH2), 22.4
(2C; CH(CH3)2) and 19.4 (ArCHCH3) (Found MH+, 352.1913;
4.1.11. 4-Phenyl-3-(2-methoxy-2-phenyl-2-trifluoromethyl-
acetyl)-oxazolidin-2-one (S,R)-syn-11
In the same way as above, n-butyl lithium (0.38 ml, 2.5 M in
hexane, 0.96 mmol), oxazolidin-2-one (R)-4 (0.13 g, 0.80 mmol)
and (R)-Mosher’s chloride (0.27 g, 0.99 mmol) gave a crude mix-
ture of oxazolidin-2-one (S,R)-anti-11. This residue was purified
by flash column chromatography eluting with light petroleum
ether (bp 40–60 °C)/diethyl ether (7:3) to give the oxazolidin-2-
one (S,R)-syn-11 (0.14 g, 48%) as a white solid; RF [light petroleum
C22H26NO3 requires 352.1907); and the oxazolidin-2-one (S,R)-
syn-14 as a white solid; mp 86–88 °C; RF [light petroleum ether
25
(bp 40–60 °C)/diethyl ether (1:1)] 0.41; ½aꢂD ¼ þ118:7 (c 6.0,
25
CHCl3) {for (R,S)-syn-14; lit. ½aꢂD ¼ ꢀ114:6 (c 4.2, CHCl3)};
mmax(CHCl3) cmꢀ11779 (C@O) and 1705 (C@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, PhCHN), 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, CH(CH3)2), 1.38 (3H, d, J 6.9,
ArCHCH3), 0.90 (3H, d, J 6.6, CHACHCHB) and 0.89 (3H, d, J 6.6,
ether (bp 40–60 °C)/diethyl ether (1:1)] 0.35; mp 173–175 °C; mmax
22
(CH2Cl2) cmꢀ1 1796 (C@O), 1702 (C@O) and 1262 (C–F); ½aꢂD
¼
ꢀ17:4 (c 1.4, CHCl3); dH (400 MHz, CDCl3) 7.45–7.42 (2H, m,
2 ꢁ CH; Ph), 7.35–7.26 (8H, m, 8 ꢁ CH; 2 ꢁ Ph), 5.50 (1H, dd, J 6.0
and 2.5, PhCHN), 4.55 (1H, t, J 6.0, CHAHBO), 4.22 (1H, dd, J 6.0
and 2.5, CHAHBO), 3.45 (3H, s, CH3O); dC (100 MHz, CDCl3) 166.3
(NC@O), 149.7 (OC@O), 138.1 (i-C; Ph), 131.8 (i-C; Ph), 129.3,1
129.2,3 129.0,1 127.6,2 126.61 and 126.52 (10 ꢁ CH; 2 ꢁ Ph), 123.3
3
3
CHA3 CHCH B); dC (100.6 MHz; CDCl3) 174.3 (NC@O), 153.3 (OC@O),
3
140.7 (i-C; Ar), 139.4 (i-C; Ar), 137.4 (i-C; Ph), 129.32 and 127.92
(4 ꢁ CH; Ar), 128.8,2 128.51 and 125.82 (5 ꢁ CH; Ph), 69.7 (CH2O),
58.1 (PhCHN), 45.1 (CH(CH3)2), 42.7 (ArCHCH3), 30.2 (CH2Ar),
22.42 (CH(CH3)2) and 19.4 (ArCHCH3) (Found MH+, 352.1909;
1
2
(1C, q, JCF 291.3, CF3), 85.6 (1C, q, JCF 26.2, PhCCF3), 69.9 (CH2O),
4
58.7 (PhCHN) and 56.0 (1C, d, JCF 2.3, CH3O); dF (378 MHz, CDCl3)
þ
ꢀ71.0 (1C, s, CF3) (Found MNH4 397.1372. C19H20F3N2O4 requires
C
C
22H26NO3 requires MH+, 352.1907; and found MNHþ4 , 369.2171;
MNH4þ, 379.1370).
22H29N2O3 requires MNH4þ, 369.2173); m/z 351.1 (10% M+),
188.1 (10, Ar(CH3)C@C@O+), 161.1 (10, Ar+CHCH3), 145.1 (100,
4.1.12. 4-Phenyl-5,5-diphenyl-3-(2-methoxy-2-phenyl-2-
trifluoromethyl-acetyl)-oxazolidin-2-one (R,S)-syn-12
ArCH2þ) and 77.1 (10, Ph+).
In the same way as above, n-butyl lithium (0.30 ml, 2.5 M in
hexane, 0.75 mmol), oxazolidin-2-one (S)-9 (0.21 g, 0.66 mmol),
and active ester (R)-11 (0.31 g, 0.78 mmol) gave a crude mixture
of oxazolidin-2-one (R,S)-syn-12. This residue was purified by flash
column chromatography eluting with light petroleum ether (bp
40–60 °C)/diethyl ether (8:2) to give the oxazolidin-2-one (R,S)-
syn-12 (0.12 g, 34%) as a white solid; RF [light petroleum ether
4.1.9. Parallel kinetic resolution of racemic oxazolidin-2-one
rac-4 using a combination of quasi-enantiomeric active esters
(R)-10 and (S)-13 for 2 h at rt
In the same way as above, n-butyl lithium (0.36 ml, 2.5 M in
hexane, 0.92 mmol), oxazolidin-2-one rac-4 (0.151 g, 0.92 mmol),
active ester (S)-13 (0.185 g, 0.46 mmol) and active ester (R)-10
(0.172 g, 0.46 mmol) gave a crude mixture of oxazolidin-2-ones
(S,S)-anti- and (S,R)-syn-14 (ratio: 21:79) and (R,R)-anti- and
(R,S)-syn-11 (ratio: 9:91). This residue was purified by flash col-
umn chromatography eluting with light petroleum ether (bp 40–
60 °C)/diethyl ether (7:3) to give the profen adducts (S,R)-syn-
and (S,S)-anti-14 (ratio 79:21, 99 mg, 61%) as a colourless oil; and
Mosher’s adducts (R,R)-syn- and (R,S)-anti-11 (ratio 82:18; 74 mg,
(bp 40–60 °C)/diethyl ether (1:1)] 0.77; mp 199–201 °C; mmax
22
(CH2Cl2) cmꢀ1 1792 (C@O), 1715 (C@O) and 1267 (C–F); ½aꢂD
¼
ꢀ2:7 (c 0.9, CHCl3); dH (400 MHz, CDCl3) 7.53–7.47 (2H, m,
2 ꢁ CH; Ph), 7.40-7.30 (4H, m, 4 ꢁ CH, 2 ꢁ Ph), 7.10 (1H, t, J 7.3,
CH; Ph), 7.05–6.85 (13H, m, 13 ꢁ CH; 4 ꢁ Ph), 6.23 (1H, s, PhCHN)
and 3.35 (3H, s, CH3O); dC (100 MHz, CDCl3) 165.6 (NC@O), 149.0
(OC@O), 141.7, 137.2, 135.1 and 131.4 (4 ꢁ i-C; Ph), 129.0,2
128.9,1 128.8,1 128.4,1 128.3,2 127.8,2 127.7,2 127.6,2 127.5,2
25
42% yield) as a colourless oil {for (R,R)-syn-11; ½aꢂD ¼ þ136:4 (c
25
1
1.07, CHCl3); and for (R,S)-syn-11; ½aꢂD ¼ þ22:3 (c 6.1, CHCl3)}.
126.4,1 125.92 and 125.52 (20 ꢁ CH; 4 ꢁ Ph), 123.3 (1C, q, JCF
2
These adducts were spectroscopically identical to those previously
obtained.
290.4, CF3), 89.2 (C(Ph)2O), 85.4 (1C, JCF 25.4, PhC), 67.6 (PhCHN)
4
and 56.0 (1C, d, JCF 2.3, CH3O); dF (378 MHz, CDCl3) ꢀ71.7 (1C, s,
CF3) (Found MNa+ 554.1548. C31H24F3NO4Na requires MNa+,
554.1550).
4.1.10. Stereospecific synthesis of 4-Phenyl-3-(2-methoxy-2-
phenyl-2-trifluoromethyl-acetyl)-oxazolidin-2-one (R,R)-anti-
11
In the same way as above, n-butyl lithium (0.44 ml, 2.5 M in
hexane, 1.10 mmol), oxazolidin-2-one (R)-4 (0.15 g, 0.95 mmol)
and active ester (R)-10 (0.45 g, 1.12 mmol) gave a crude mixture
of oxazolidin-2-one (R,R)-anti-11. This residue was purified by
flash column chromatography eluting with light petroleum ether
(bp 40–60 °C)/diethyl ether (7:3) to give the oxazolidin-2-one
(R,R)-anti-11 (0.16 g, 44%) as a pale yellow oil; RF [light petroleum
4.1.13. (S,S)-4-Phenyl-5,5-diphenyl-3-(2-methoxy-2-phenyl-2-
trifluoromethyl-acetyl)-oxazolidin-2-one anti-12
In the same way as above, n-butyl lithium (0.30 ml, 2.5 M in
hexane, 0.75 mmol), oxazolidin-2-one (S)-9 (0.21 g, 0.66 mmol)
and active ester (S)-10 (0.31 g, 0.78 mmol) gave a crude mixture
of oxazolidin-2-one anti-12. This residue was purified by flash col-
umn chromatography eluting with light petroleum ether (bp 40–
60 °C)/diethyl ether (8:2) to give the oxazolidin-2-one (R,S)-anti-
12 (0.15 g, 43%) as a white solid; RF [light petroleum ether (bp
40–60 °C)/diethyl ether (1:1)] 0.77; mp 151–154 °C; mmax (CH2Cl2)
ether (bp 40–60 °C)/diethyl ether (1:1)] 0.13; mp 86–88 °C; mmax
22
(CH2Cl2) cmꢀ1 1803 (C@O), 1702 (C@O) and 1256 (C–F); ½aꢂD
¼
22
þ136:4 (c 1.07, CHCl3); dH (400 MHz, CDCl3) 7.34–7.13 (10H, m,
2 ꢁ CH; 2 ꢁ Ph), 5.25 (1H, dd, J 8.0 and 2.0, PhCHN), 4.43 (1H, dd,
J 8.8 and 8.0, CHAHBO), 4.08 (1H, dd, J 8.8 and 2.0, CHAHBO) and
3.42 (3H, s, CH3O); dC (100 MHz, CDCl3) 165.2 (NC@O), 149.9
(OC@O), 138.5 (i-C; Ph), 132.0 (i-C; Ph), 129.4,1 129.1,3 129.0,1
cmꢀ1 1807 (C@O), 1702 (C@O) and 1256 (C–F); ½aꢂD ¼ ꢀ232:4 (c
1.05, CHCl3); dH (400 MHz, CDCl3) 7.52 (2H, d, J 7.4, 2 ꢁ CH; Ph),
7.35-7.18 (8H, m, 8 ꢁ CH, 2 ꢁ Ph), 7.09–7.05 (3H, m, 3 ꢁ CH,
2 ꢁ Ph), 6.95 (7H, m, 7 ꢁ CH; 3 ꢁ Ph), 6.00 (1H, s, PhCHN) and
2.92 (3H, s, CH3O); dC (100 MHz, CDCl3) 165.3 (NC@O), 149.0
(OC@O), 141.2, 136.9, 134.8 and 132.1 (4 ꢁ i-C; Ph), 129.3,1
129.0,2 128.8,1 128.5,1 128.3,2 128.0,2 127.7,2 127.6,1 127.4,2
1
128.0,2 126.61 and 126.02 (10 ꢁ CH; 2 ꢁ Ph), 123.2 (1C, q, JCF
2
290.4, CF3), 85.7 (1C, q, JCF 26.1, PhCCF3), 70.0 (CH2O), 58.8
4
1
(PhCHN) and 56.1 (1C, d, JCF 2.3, CH3O); dF (378 MHz, CDCl3)
126.5,2 125.82 and 125.52 (20 ꢁ CH; 4 ꢁ Ph), 123.1 (1C, q, JCF

1282
S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1274–1284
2
290.5, CF3), 89.1 (C(Ph)2O), 85.6 (1C, JCF 25.4, PhC), 67.7 (PhCHN)
165.1 (C@O), 143.9, 143.7, 136.8 and 131.7 (4 ꢁ i-C; 4 ꢁ Ph),
129.1,1 128.5,4 128.4,2 128.1,2 127.9,2 128.8,2 127.7,1 127.2,1
127.1,1 125.8,2 and 125.4,2 (20 ꢁ CH; 4 ꢁ Ph), 123.7 (1C, q,
4
and 55.3 (1C, d, JCF 2.3, CH3O); dF (378 MHz, CDCl3) ꢀ70.3 (1C, s,
CF3) (Found MH+ 532.1732. C31H25F3NO4 requires MH+, 532.1732).
1
1JC,F = 289, CF3), 83.9 (1C, q, JC,F = 26.1, PhC), 80.8 (CPh2) 58.8
4.1.14. Hydrolysis of oxazolidin-2-one (S,R)-syn-11; synthesis of
2-methoxy-2-phenyl-2-trifluoromethyl acetic acid (S)-8
(CH3O) and 54.7 (PhCHN); dF (378 MHz, CDCl3) ꢀ69.1 (1C, s, CF3)
þ
þ
(Found MNH4
252.0842).
252.0844. C10H13F3NO3 requires MNH4 ,
Lithium hydroxide monohydrate (11 mg, 0.26 mmol) was
slowly added to a stirred solution of oxazolidin-2-one (S,R)-syn-
11 (50 mg, 0.13 mmol) and hydrogen peroxide (9 mg, 0.07 ml,
0.26 mmol, 3.53 M in H2O) in THF/water (1:1; 5 ml). The reaction
mixture was stirred at room temperature for 12 h. The reaction
was quenched with water (10 ml) and extracted with dichloro-
methane (3 ꢁ 10 ml). The combined organic layers were dried
(over MgSO4) and evaporated under reduced pressure and purified
by column chromatography to give oxazolidin-2-one (R)-4 (1 mg,
ꢃ5%); RF [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)]
0.27; and amide (S,R)-15 (37 mg, 80%) as a white solid; RF [light
petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.50; mp 160–
4.1.16. Hydrolysis of oxazolidin-2-one (R,S)-syn-12 with 24% de
In the same way as above, oxazolidin-2-one (R,S)-syn-12 (24%
de) (0.15 g, 0.28 mmol), lithium hydroxide monohydrate (24 mg,
0.54 mmol) and hydrogen peroxide (18 mg, 0.15 ml, 0.54 mmol,
3.53 M in H2O) in THF/water (1:1; 5 ml) gave after purification
by aqueous extraction 2-methoxy-2-phenyl-2-trifluoromethyl ace-
22
tic acid (+)-(R)-8 (17 mg, 26%) as a liquid; ꢃ24% ee;28 ½aꢂD ¼ þ16:9
(c 3.4, CHCl3) {lit.29 [a]D = +69.8 (c 0.22, EtOH)}, which was spectro-
scopically identical to that previously obtained.
20
163 °C; ½aꢂD ¼ ꢀ42:8 (c 1.1, EtOH); mmax(CHCl3) cmꢀ1 3020 (OH
4.1.17. Characterisation data for the formation of amide (R,R)-
anti-17 [derived from n-BuOLi addition to oxazolidin-2-one
(R,R)-anti-11]
and NH), 1782 (C@O) and 1701 (C@O); dH (400 MHz; CDCl3)
7.51–7.48 (3H, m, 3 ꢁ CH; 2 ꢁ Ph), 7.40–7.19 (9H, m, 7 ꢁ CH
(2 ꢁ Ph), OH and NH), 5.06 (1H, dt, J 7.7 and 4.9, PhCHN), 3.86–
3.78 (2H, dABq, CH2OH) and 3.31 (3H, s, CH3O); dC (100 MHz;
CDCl3) 166.7 (C@O), 138.1 and 132.2 (2 ꢁ i-C; Ph), 129.6,1 128.9,2
128.8,2 128.0,1 127.8,2 and 126.62 (10 ꢁ CH; 2 ꢁ Ph), 123.8 (1C, q,
Colourless oil; RF [light petroleum ether (bp 40–60 °C)/diethyl
22
ether (1:1)] 0.5; ½aꢂD ¼ ꢀ24:75 (c 3.2, CHCl3); mmax(CH2Cl2) cmꢀ1
1742 (C@O) and 1702 (C@O); dH (400 MHz, CDCl3) 7.37–7.32 (2H,
m, 2 ꢁ CH; Ph), 7.31–7.21 (6H, m, 6 ꢁ CH; 2 ꢁ Ph), 7.16–7.11 (2H,
m, 2 ꢁ CH; Ph), 5.27 (1H, td, J 7.6 and 3.4, PhCHN), 4.34 (2H, dABq,
J 7.6 and 11.6, CH2O), 4.07 (2H, td, J 6.8 and 3.2, CH2O; OBu), 3.40
(3H, s, CH3O), 1.56 (2H, appears as a quintet, J 6.7, CH2), 1.31 (2H,
appears as a sextet, J 7.5, CH2) and 0.85 (3H, t, J 7.3, CH3CH2); dC
(100 MHz, CDCl3) 166.2 (NC@O), 155.3 (OC@O), 137.1 (i-C; Ph),
132.3 (i-C; Ph), 129.5,1 128.8,2 128.4,2 128.2,1 127.52 and 126.72
1
1JC,F = 288, CF3), 84.2 (1C, q, JC,F = 24.7, PhC), 66.1 (CH2O), 55.5
(CH3O) and 54.9 (PhCHN); dF (378 MHz, CDCl3) ꢀ70.1 (1C, s, CF3)
(Found MH+ 354.1310. C18H19F3O3N+ requires MH+, 354.1312).
The aqueous phase was acidified using HCl (3 M HCl) until the
pH 3, extracted with diethyl ether (3 ꢁ 10 ml). The combined
organic phases were dried (over MgSO4) and evaporated under
1
2
reduced pressure to give (ꢀ)-2-methoxy-2-phenyl-2-trifluoro-
(10 ꢁ CH; 2 ꢁ Ph), 123.9 (1C, q, JCF 288.7, CF3), 84.0 (1C, q, JCF
25.9, PhCCF3), 68.6 (CH2O), 68.4 (CH2O), 55.1 (PhCHN), 52.7
(OCH3), 30.5 (CH2), 18.8 (CH2) and 13.6 (CH3); dF (378 MHz, CDCl3)
ꢀ68.8 (1C, s, CF3) (Found MH+ 454.1837. C23H27F3NO5 requires
MH+, 454.1836).
20
methyl acetic acid (S)-8 (ꢃ2 mg, 6%) as an oil; >95% ee;28 ½aꢂD
¼
22
ꢀ65:0 (c 0.4, CHCl3) {lit.29 ½aꢂD ¼ ꢀ71:6 (c 0.23, EtOH); lit.30
[a]D = ꢀ69.0 (c 1.13, MeOH); lit.31 [a]D = ꢀ69.5 (c 1.2, MeOH)};
mmax(CHCl3) cmꢀ1 3015 (OH), 1785w (C@O) and 1729 (C@O), dH
(400 MHz; CDCl3) 7.58–7.57 (2H, m, 2 ꢁ CH; Ph), 7.45–7.37 (3H,
m, 3 ꢁ CH; Ph), 6.37 (1H, br s, OH) and 3.53 (3H, s, CH3O); dC
(100 MHz; CDCl3) 166.9 (C@O), 131.2 (i-C; Ph), 129.9,1 128.6,2
4.1.18. Characterisation data for the formation of amide (S,R)-
syn-17 [derived from n-BuOLi addition to oxazolidin-2-one
(S,R)-syn-11]
and 127.32 (5 ꢁ CH; Ph), 125.6 (1C, q, JC,F = 289 Hz, CF3), 88.2
1
1
þ
(1C, q, JC,F = 27.5, PhC) and 55.1 (CH3O) (Found MNH4
Colourless oil; RF [light petroleum ether (bp 40–60 °C)/diethyl
22
252.0844. C10H13F3NO3 requires MNH4þ, 252.0842).
ether (1:1)] 0.5; ½aꢂD ¼ ꢀ19:2 (c 3.9, CHCl3); mmax(CH2Cl2) cmꢀ1
1742 (C@O) and 1702 (C@O); dH (400 MHz, CDCl3) 7.55–7.51 (2H,
m, 2 ꢁ CH; Ph), 7.39–7.36 (4H, m, 4 ꢁ CH; 2 ꢁ Ph), 7.35–7.33 (2H,
m, 2 ꢁ CH; Ph), 7.32–7.29 (2H, m, 2 ꢁ CH; Ph), 5.27 (1H, dt, J 8.4
and 6.0, PhCHN), 4.38 (2H, d, J 6.0, CH2O), 4.08 (2H, td, J 6.8 and
3.8, CH2O; OBu), 3.36 (3H, s, CH3O), 1.59 (2H, appears as a quintet,
J 6.7, CH2), 1.35 (2H, appears as a sextet, J 7.3, CH2) and 0.85 (3H, t, J
7.3, CH3CH2); dC (100 MHz, CDCl3) 166.2 (NC@O), 155.3 (OC@O),
137.2 (i-C; Ph), 132.3 (i-C; Ph), 129.5,1 128.9,2 128.5,2 128.2,1
4.1.15. Hydrolysis of oxazolidin-2-one (R,S)-syn-12; synthesis of
2-methoxy-2-phenyl-2-trifluoromethyl acetic acid (R)-8
In the same way as above, 2-methoxy-2-phenyl-2-trifluoro-
methyl acetic acid (S)-8, oxazolidin-2-one (R,S)-syn-12 (49 mg,
92 lmol), lithium hydroxide monohydrate (8 mg, 0.18 mmol) and
hydrogen peroxide (6 mg, 0.05 ml, 0.18 mmol, 3.53 M in H2O) in
THF/water (1:1; 5 ml) gave after purification by aqueous extraction
1
(+)-2-methoxy-2-phenyl-2-trifluoromethyl acetic acid (R)-8
127.82 and 126.62 (10 ꢁ CH; 2 ꢁ Ph), 123.7 (1C, q, JCF 288.3, CF3),
22
2
(10 mg, 46%) as a liquid; ½aꢂD ¼ þ67:0 (c 0.6, CHCl3) {lit.29 [a]D
=
84.1 (1C, q, JCF 26.8, PhCCF3), 68.7 (CH2O), 68.3 (CH2O), 54.9
+69.8 (c 0.22, EtOH)}, which was spectroscopically identical to
those previously obtained. The combined organic layers were dried
over MgSO4 and evaporated under reduced pressure and purified
by column chromatography to give the 4,5,5-triphenyl-oxazoli-
din-2-one (S)-9 (5 mg, 17%); RF [light petroleum ether (bp 40-
60 °C)/diethyl ether (1:1)] 0.13; and the amide (S,R)-16 (11 mg,
24%) as a white solid; RF [light petroleum ether (bp 40–60 °C)/
(PhCHN), 52.5 (OCH3), 30.6 (CH2), 18.8 (CH2) and 13.6 (CH3); dF
(378 MHz, CDCl3) ꢀ68.7 (1C, s, CF3) (Found MH+ 454.1835.
C
23H27F3NO5 requires MH+, 454.1836).
4.1.19. Characterisation data for the formation of amides
(RS,RS)-anti- and (RS,SR)-syn-17 [derived from n-BuOLi addition
to oxazolidin-2-ones (RS,RS)-anti- and (RS,SR)-syn-11 ratio
(21:79)]
Amide (RS,RS)-anti- and (RS,SR)-syn-17 (ratio: 21:79); colourless
oil; RF [light petroleum ether (bp 40–60 °C)/diethyl ether (1:1)] 0.5;
mmax(CH2Cl2) cmꢀ1 1743 (C@O) and 1700 (C@O); dH (400 MHz,
CDCl3) 7.51–7.45 (2H, m, 2 ꢁ CH; PhS), 7.40–7.20 (16H, m, 16
2 ꢁ CH; 2 ꢁ PhS+A), 7.15–7.11 (2H, m, 2 ꢁ CH; PhA), 5.27 (1H, td, J
7.6 and 3.4, PhCHNS+A), 4.34 (4H, dABq, J 7.6 and 11.6, CH2OS+A),
20
diethyl ether (1:1)] 0.41; mp 156–160 °C; ½aꢂD ¼ ꢀ132:0 (c 1.6,
CHCl3); mmax(CHCl3) cmꢀ1 1781 (C@O) and 1704 (C@O); dH
(400 MHz; CDCl3) 7.86 (1H, br d, J 9.1, NH), 7.50 (2H, dt, J 6.7
and 1.6, 2 ꢁ CH; Ph), 7.28–7.20 (3H, m, 3 ꢁ CH; 2 ꢁ Ph), 7.20–
7.14 (4H, m, 4 ꢁ CH; 2 ꢁ Ph), 7.14–7.05 (6H, m, 6 ꢁ CH; 2 ꢁ Ph),
7.05–6.99 (5H, m, 5 ꢁ CH; 2 ꢁ Ph), 6.01 (1H, d, J 9.1, PhCHN),
3.05 (3H, s, CH3O) and 2.58 (1H, s, OH); dC (100 MHz; CDCl3)

S. Chavda et al. / Tetrahedron: Asymmetry 19 (2008) 1274–1284
1283
4.07 (2H, td, J 6.8 and 3.2, CH2O; OBuA), 3.95 (2H, td, J 6.8 and 3.2,
(CH3O), 30.6 (CH2), 18.7 (CH2) and 13.6 (CH3); dF (378 MHz, CDCl3)
ꢀ69.0 (1C, s, CF3) (Found MH+ 606.2465. C35H35F3NO5 requires
MH+, 606.2462); and the amide (R,S)-syn-16 (4 mg, 3%) as a colour-
less oil, which was spectroscopically identical to that previously
obtained.
CH2O; OBuS), 3.40 (3H, s, CH3OA), 3.31 (3H, s, CH3OS), 1.60–1.50
(4H, m, CHS2þA), 1.31 (4H, m, CH2SþA), 0.86 (3H, t, J 7.3, CH3CHA)
2
and 0.85 (3H, t, J 7.3, CH3CHS ); dC (100 MHz, CDCl3) 166.2 (2C;
2
NC@OS+A), 155.3 (2C; OC@OS+A), 137.1 (2C; i-C; PhS+A), 132.3 (i-C;
PhA), 132.2 (i-C; PhS), 129.5S,1 129.4A,1128.9S,2 128.8A,2 128.5S,2
128.4A,2 128.2A,1 128.1S,1 127.8S,2 127.5A,2 126.7S,2 and 126.6A,2
4.1.23. Synthesis of (2R,2S)-(2-phenyl-2-methoxy-2-trifluoro-
ethanonyl){2-[(butoxycarbonyl)oxy]-2,2-diphenyl-2-phenyl-
ethyl} carbamate (R,S)-syn-18 (using 3 equiv of n-BuLi)
In the same way as above, n-butyl lithium (0.41 ml, 2.5 M in
hexane, 1.03 mmol), butanol (0.127 g, 1.71 mmol) and oxazoli-
din-2-one (R,S)-syn-12 (0.13 g, 0.34 mmol) gave a crude mixture
of amides (R,S)-syn-16 and (R,S)-syn-18 (ratio 23:77). This residue
was purified by flash column chromatography eluting with light
petroleum ether (bp 40–60 °C)/diethyl ether (9:1?3:7) to give
the amides (R,S)-anti-16 (4 mg, 3%) and (R,S)-anti-18 (42 mg,
27%) as colourless oils, both of which were spectroscopically iden-
tical to that previously obtained.
(20 ꢁ CH; 2 ꢁ PhS+A), 123.7 (1C, q, JCF 289.5, CFS3), 123.6 (1C, q,
1
1JCF 288.7, CFA3 ), 84.1 (1C, q, JCF 25.9, PhCCFS3), 84.0 (1C, q, JCF
25.9, PhCCFA3 ), 68.7 (CH2OS), 68.6 (CH2OA), 68.3 (CH2OS), 68.3
(CH2OA), 55.1 (PhCHNA), 54.9 (PhCHNS), 52.7 (OCHA3 ), 52.5
(OCHS3), 30.5 (2C; CH2SþA), 18.8 (2 C; CH2SþA), 13.6 (CHS3) and 13.6
(CHA); dF (378 MHz, CDCl3) ꢀ68.8 (1C, s, CFA) and ꢀ68.7 (1C, s,
2
2
3
3
CFS3) (Found MH+ 454.1835. C23H27F3NO5 requires MH+, 454.1836).
4.1.20. Characterisation data for (R)-butyl 2-methoxy-2-
phenyl-2-trifluoromethyl acetate 8
Colourless oil; RF [light petroleum ether (bp 40–60 °C)/diethyl
22
ether (1:1)] 0.76; mmax(CH2Cl2) cmꢀ1 1747 (C@O); ½aꢂD ¼ þ48:0 (c
5.8, CHCl3); dH (400 MHz, CDCl3) 7.51–7.45 (2H, m, 2 ꢁ CH; PhS),
7.53–7.48 (2H, m, 2 ꢁ CH; Ph), 7.41–7.36 (3H, m, 3 ꢁ CH; Ph),
Acknowledgements
4
4.36–4.25 (2H, m, CH2O), 3.53 (3H, q, JCF 1.1, OCH3), 1.70–1.62
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 thank Onyx Scientific Limited (Drs Tony Flinn
and Julian Northen) for their interest in this project.
(2H, m, CH2), 1.39–1.30 (2H, appears as a br sextet, J 7.3, CH2)
and 0.89 (3H, t, J 7.5, CH3CH2); dC (100 MHz, CDCl3) 166.5 (C@O),
132.3 (i-C; Ph), 129.5,1 128.32 and 127.22 (5 ꢁ CH; Ph), 124.1 (1C,
1
2
q, JCF 286.5, CF3), 84.5 (1C, q, JCF 26.7, PhCCF3), 66.2 (CH2O),
55.3 (OCH3), 30.3 (CH2), 18.9 (CH2) and 13.4 (CH3); dF (378 MHz,
þ
CDCl3) ꢀ71.5 (1C, s, CF3); (Found MNH4 308.1467. C14H21F3NO3
requires MNH4þ, 308.1468).
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22
{½aꢂD ¼ ꢀ48:3 (c 6.2, CHCl3) [for a ratio 89:11 of (R,S)-syn-18:
(R,S)-syn-12]}; mmax(CH2Cl2) cmꢀ1 1740 (C@O) and 1709 (C@O);
dH (400 MHz, CDCl3) 8.90 (1H, br s, NH), 7.55 (2H, br d, J 7.1,
2 ꢁ CH; Ph), 7.45–7.35 (3H, m, 4 ꢁ CH; 2 ꢁ Ph), 7.28–7.14 (11H,
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7.3, CH3CH2); dC (100 MHz, CDCl3) 165.2 (NC@O), 154.1 (OC@O),
141.5, 139.6, 136.5 and 132.4 (4 ꢁ i-C; 4 ꢁ Ph), 129.3,1 128.5,2
128.4,2 128.1,2 127.9,1 127.8,5 127.7,1 127.5,2 127.32 and 127.02
1
(20 ꢁ CH; 4 ꢁ Ph), 123.6 (1C, q, JC,F = 288, CF3), 89.1 (CPh2), 83.4
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(1C, q, JC,F = 25.2, PhCCF3), 68.3 (CH2O), 57.9 (PhCHN), 55.1

1284
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