Synthesis, characterisation and application of enantiomeric isotopomers of Evans' oxazolidinones

Article abstract of DOI:10.1016/j.tetasy.2007.01.003

The synthesis of a series of enantiomerically pure deuterium-labelled isotopomeric Evans' oxazolidinones is discussed.

Full text of DOI:10.1016/j.tetasy.2007.01.003

Tetrahedron: Asymmetry 17 (2006) 3406–3422
Synthesis, characterisation and application of enantiomeric
isotopomers of Evans’ oxazolidinones
Ewan Boyd,a Sameer Chavda,b Elliot Coulbeck,b Gregory S. Coumbarides,c Marco Dingjan,b
Jason Eames,b,* Anthony Flinn,d Aarti K. Krishnamurthy,b Mariam Namutebi,c
Julian Northend and Yonas Yohannesc
aSyngenta, Grangemouth Manufacturing Centre, Earls Road, Grangemouth, Scotland FX3 8XG, UK
bDepartment of Chemistry, University of Hull, Cottingham Road, Kingston upon Hull HU6 7RX, UK
cDepartment of Chemistry, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
dOnyx Scientific Limited, Units 97-98, Silverbriar, Sunderland Enterprise Park East, Sunderland SR5 2TQ, UK
Received 29 November 2006; accepted 4 January 2007
Abstract—The synthesis of a series of enantiomerically pure deuterium-labelled isotopomeric Evans’ oxazolidinones is discussed.
ꢀ 2007 Published by Elsevier Ltd.
HO2C
Ph
H
BuO2C
Ph
H
1. Introduction
The synthesis of enantiomerically pure profens,1 such as
ibuprofen2 and naproxen,3 is well documented. In particu-
lar, the use of quasi-enantiomeric components, such as (S)-
1 and (R)-[D3]-1,1 within organic synthesis is developing
into an exciting area (Scheme 1).2 These species are fasci-
nating as they behave as if they were a pair of distinguish-
able enantiomers. Most importantly, due to their
distinguishability the relative composition can easily be
measured using standard instrumentation (e.g., NMR spec-
troscopy, mass spectrometry and HPLC).
CH3
CH3
(
S
)-1
(
S
)-2
lipase-mediated
esterification
HO2C
Ph
H
BuO2C
Ph
H
CD3
)-[D ]-1
CD3
)-[D ]-2
(
R
3
(
R
3
up to 25% ee
(at 30% conversion)
Within this field, Reetz1 has used this particular pair of
quasi-enantiomeric 2-phenylpropionic acids, (S)-1 and
(R)-[D3]-1,1 as a chiral probe for determining the efficiency
of a lipase-mediated esterification (Scheme 2). This kinetic
resolution was efficiently monitored in situ by the use of
Scheme 2. Kinetic separation of isotopomers (S)-1 and (R)-[D3]-1.
mass spectrometry as starting precursors (S)-1 and (R)-
[D3]-1, and product butyl esters (S)-2 and (R)-[D3]-2-d3
have different molecular masses. The quasi-enantiomeric
excess of product 2 was found to increase linearly with con-
version; the highest enantiomeric excess (25% ee) was ob-
tained at approximately 30% conversion (Scheme 2). To
ensure that there was no secondary kinetic isotope effect,
this reaction was monitored additionally using a racemic
sample of 2-phenylpropionic acid 1, which gave a compara-
ble stereoselectivity.
H
HO2C
Ph
HO2C
Ph
H
CH3
CD3
)-[D3]-1
(S)-1
(R
Scheme 1. Quasi-enantiomeric isotopomers (S)-1 and (R)-[D3]-1.
*
This strategy has recently been used by Harada3 to measure
the stereochemical efficiency of a simple esterification
Corresponding author. Tel.: +44 1482 466401; fax: +44 1482 466410;
e-mail: j.eames@hull.ac.uk
0957-4166/$ - see front matter ꢀ 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2007.01.003

E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
3407
CH3
OCH3
O
O
H
CH3
O
H3C
CH3(CH2)13
H
HO2C
CH3
OCH3
OCD3
CH3
O
CH3(CH2)13
CH3(CH2)13
H3C
OH
H
( )-4
S
( )-3
S
(S,S)-5
DCC
(R,R)-[D3]-5
OCD3
CH3
O
H
CH3
O
O
H3C
CH3(CH2)13
H
O
OCD3
CH3
CH3
OCH3
HO2C
CH3(CH2)13
OH
CH3
CH3(CH2)13
H
(R)-3
(R)-[D3]-4
(
S,R)-[D3]-5
(R,S)-5
Scheme 3. Kinetic resolution of alcohol 3 using quasi-enantiomeric isotopomers (S)-4 and (R)-[D3]-4.
reaction between a racemic alcohol rac-3 {(S)-3 and (R)-3
as shown in Scheme 3} and a quasi-enantiomeric pair of
carboxylic acids (S)-4 and (R)-[D3]-4, to give the corre-
sponding ester 5. Harada3 has shown that the mutual rec-
ognition of a scalemic sample of alcohol 3 (of unknown
composition) with an equimolar mixture of quasi-enantio-
meric carboxylic acids (S)-4 and (R)-[D3]-4 (mediated by
the addition of racemic DCC), gave a diastereoisomeric
pair of quasi-enantiomers (S,S)-5 and (S,R)-[D3]-5, and
(R,S)-5 and (R,R)-[D3]-5, respectively (Scheme 3). The
enantiomeric excess of the scalemic alcohol 3 was deter-
mined by 1H NMR spectroscopy by comparing the relative
amounts of each adduct within each diastereoisomeric pair.
rium-labelled quasi-enantiomeric combinations of isotopo-
mers of Evans’ oxazolidinones, such as (R)-6 and (S)-[D2]-
6, and their application as chiral probes for monitoring the
efficiency of novel parallel kinetic resolutions (Scheme 5).
To this aim, we were required to synthesise a series of enan-
tiomerically pure deuterium-labelled oxazolidinones (S)-
[D2]-6, (R)-[D2]-7, (R)-[D2]-17, (S)-[D2]-20 and (S)-[D2]-21
(Schemes 6 and 7). For synthetic ease, we first chose to
incorporate the di-deuterium labels at the C(5)-position
of the oxazolidinone using Meyers’7 original lithium alu-
minium hydride protocol (Scheme 6). These oxazolidinones
(S)-[D2]-6, (R)-[D2]-7 and (R)-[D2]-17 were efficiently syn-
thesised in a good yield by the reduction of the correspond-
ing a-amino acids (S)-11, (R)-12 and (R)-13 using lithium
aluminium deuteride (LiAlD4) {to give the corresponding
dideuterio-a-amino alcohols (S)-[D2]-14, (R)-[D2]-15 and
(R)-[D2]-16}, and cyclisation by the addition of diethylcar-
bonate in the presence of a sub-stoichiometric amount of
2. Results and discussion
We have recently become interested in the parallel kinetic
resolution4 of profen adducts,5,6 such as pentafluorophenyl
2-phenylpropionate rac-8 (derived from 2-phenyl propionic
acid) using two complementary quasi-enantiomeric Evans’
oxazolidinones (R)-6 and (S)-7 to give two separable ad-
ducts syn-9 and syn-10, respectively (Scheme 4). The levels
of mutual recognition between these substrates (R)-6 and
(S)-8, and (S)-7 and (R)-8 were shown to be excellent
(>76% de).
O
O
HN
O
HN
O
D
Ph
Ph
D
(
S
)-[D2]-6
(R)-6
In an attempt to extend the versatility of this resolution
methodology, we were interested in the synthesis of deute-
Scheme 5. Quasi-enantiomeric isotopomers (R)-6 and (S)-[D2]-6.
O
O
O
O
O
O
1. n-BuLi
THF, -78 oC
Ph
Me
Ph
N
O
N
O
HN
O
HN
O
Ph
CO2C6F5
(2 equiv.)
2.
H
H
Me
Ph
i-Pr
Ph
i-Pr
H
CH3
(R)-6
(S)-7
syn-:anti-9
95:5; 60%
syn-:anti-10
88:12; 60%
rac-8
Scheme 4. Parallel kinetic resolution of active ester rac-8.

3408
E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
O
H2N
R
OH
H2N
R
K2CO3
LiAlD4
HN
R
O
D
CO2H
D
EtOCO2Et
then HCl, H2O
D
D
11-13
[D2]-14-16
[D2]-6, [D2]-7, [D2]-17
oxazolidinone
S)-[D2]-6; 40%
Entry
amino acid
amino alcohol
(
(
S
)-11; R = Ph
)-12; R = -Pr
)-13; R = CH2Ph
(
S
)-[D2]-14; 79%
)-[D2]-15; 77%
1
2
3
(
R
(R
)-[D2]-7; 57%
(R
i
(R
(
R
)-[D2]-16; 93%
(R)-[D2]-17; 40%
Scheme 6. LiAID4 reduction of a-amino-acids 11–13.
BocHN
OH
BocHN
LiAlD4
then HCl, H2O
CO2CH3
D
4-TBDMSOC6H4
D
4-TBDMSOC6H4
(
S
)-[D2]-19; 94%
S
( )-18
O
O
HN
O
D
HN
O
D
SOCl2
D
D
4-HOC6H4
4-TBDMSOC6H4
S
( )-[D2]-21; 11%
S
( )-[D2]-20; 45%
Scheme 7. Synthesis of oxazolidinones (S)-[D2]-20 and (S)-[D2]-21.
potassium carbonate (Scheme 6). The remaining oxazolid-
inones (S)-[D2]-20 and (S)-[D2]-21 were efficiently synthes-
ised by the reduction of the protected ester (S)-18 {using
lithium aluminium deuteride to give (S)-[D2]-19 in 94%
yield}, followed by a thionyl chloride mediated cyclisation
using methodology reported by Fox8 (Scheme 7).
and (S)-[D2]-6 (Scheme 10). Deprotonation of oxazolidi-
nones (R)-6 and (S)-[D2]-6 with n-butyl lithium in THF
at ꢁ78 ꢁC, followed by addition of benzoyl chloride gave
an inseparable equimolar mixture of the quasi-enantio-
meric oxazolidinones (R)-22 and (S)-[D2]-22 in good yield
(Scheme 10). The relative proportions of each isotopomer
(R)-22 and (S)-[D2]-22 were easily confirmed by either mass
1
With these deuterium-labelled oxazolidinones (S)-[D2]-6,
(R)-[D2]-7, (R)-[D2]-17, (S)-[D2]-20 and (S)-[D2]-21 in
hand, we next probed their combination with an equimolar
amount of their quasi-enantiomeric partner (R)-6, (S)-7,
(S)-17, (R)-20 and (R)-21, respectively, to give the corre-
sponding quasi-enantiomeric mixtures of (R)-6 and
(S)-[D2]-6, (S)-7 and (R)-[D2]-7, (S)-17 and (R)-[D2]-17,
(R)-20 and (S)-[D2]-20, and (R)-21 and (S)-[D2]-21 (Scheme
8). By proton and carbon NMR spectroscopy, these quasi-
racemic mixtures (e.g., A and [D2]-B) were clearly distin-
guishable (Scheme 9). It is interesting to note, for the CHN
group within the D-labelled oxazolidinones, [D2]-B, there
was a noticeable negative isotope shift for both hydrogen,
Hb (ꢀ0.010–0.043 ppm), and carbon, Cb (ꢀ0.175–
spectrometry or H NMR spectroscopy. This assignment
proved identical to that obtained by pre-mixing an equimo-
lar amount of each individual quasi-enantiomer of (R)-22
and (S)-[D2]-22 (derived from (R)-6 and (S)-[D2]-6, respec-
tively) (Scheme 10).
We next studied the parallel kinetic resolution of a series of
structurally related racemic pentafluorophenate esters
(rac)-27–30 using an equimolar combination of quasi-enan-
tiomeric oxazolidinones (R)-6 and (S)-[D2]-6 (Scheme 11
and 12). These active esters rac-27–30 were efficiently syn-
thesised in a good yield by the sequential addition of N,N0-
dicyclohexylcarbimide (DCC) and pentafluorophenol
(C6F5OH) to a stirred solution of the corresponding car-
boxylic acids rac-23-26 in dichloromethane (Scheme 11).
1
0.183 ppm) as determined by H and 13C NMR spectro-
scopy, respectively. By mass spectrometry, an approximate
equimolar amount of each quasi-enantiomeric isotopomer
was present.9
Deprotonation of the equimolar combination of oxazolid-
inones, (R)-6 and (S)-[D2]-6, with n-butyl lithium at ꢁ78 ꢁC
in THF, followed by the addition of pentafluorophenyl
active esters rac-27–30 in THF, gave a pair of separable
diastereoisomeric adducts, syn-31-34 and syn-[D2]-31–34
With these oxazolidinones in hand, we first probed the ben-
zoylation of an equimolar mixture of oxazolidinones (R)-6

E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
3409
O
O
O
O
43%
O
O
1.
n
-BuLi,
(R)-6
+
(S)-[D2]-6
HN
O
HN
O
THF, -78 oC
Ph
N
O
Ph
N
O
2. PhCOCl
D
D
D
Ph
Ph
Ph
Ph
D
(
S
)-[D ]-6
(
R
)-6
2
(S)-[D2]-22
(R
)-22
50%
O
O
O
O
O
1.
n
-BuLi,
THF, -78 oC
HN
O
Ph
N
O
HN
O
HN
O
2. PhCOCl
D
Ph
Ph
i
-Pr
i-Pr
D
(R
)-6
(R
)-22
(
R
)-[D ]-7
(
S
)-7
2
61%
O
O
O
1.
n
-BuLi,
THF, -78 oC
O
O
HN
O
D
Ph
N
O
2. PhCOCl
HN
O
HN
O
D
D
Ph
)-[D2]-6
Ph
D
D
(
S
PhCH2
PhCH2
(S)-[D2]-22
D
(R)-[D2]-17
(
S
)-17
Scheme 10. Benzoylation of isotopomeric oxazolidinones 6.
O
O
(syn-A and syn-[D2]-B), and anti-31-34 and anti-[D2]-31–34
(anti-A and anti-[D2]-A), respectively (Scheme 12). The lev-
els of mutual diastereoselectivity (syn- to anti-) were excel-
lent, ranging from 95:5 (Scheme 12: entry 3) to >98:2
(Scheme 12: entry 2). Each pair of diastereoisomeric ad-
ducts (e.g., for oxazolidinones syn-32 and syn-[D2]-32,
and anti-32 and anti-[D2]-32—see Scheme 12: entry 2) con-
tain a near equimolar amount of two both isotopomers; for
syn-32 and syn-[D2]-32; ratio 50:50 ( 2%), and anti-32 and
anti-[D2]-32; ratio 50:50 ( 2%). The levels of diastereocon-
trol (90–96% de) and relative isotopomeric composition
HN
O
HN
O
D
4-TBMDSOC6H4
4-TBMDSOC6H4
D
(
R
)-20
(
)-[D ]-20
2
S
O
O
HN
O
HN
O
D
4-HOC6H4
4-HOC6H4
D
1
were determined by H NMR spectroscopy. This relative
(
S
)-[D ]-21
2
(
R
)-21
composition was verified through a combination of column
chromatography and mass spectrometry to determine the
relative diastereoselectivity and isotopic composition,
Scheme 8. Quasi-enantiomeric isotopomers oxazolidinones 6, 7, 17, 20
and 21.
O
O
HN
O
HN
O
Ha Ca
R
Hb Cb
R
D
D
A
[D2]-B
isotope shifts
quasi-enantiomeric
oxazolidinones A and B
Δ δ(Ca - Cb) ppm
Δ δ(Ha - Hb) ppm
Entry
1
2
0.175 ppm
0.191 ppm
0.183 ppm
(
R
)-12 + (
)-7 + (
)-17 + (
)-20 + (
S
)-[D2]-6; R = Ph
)-[D2]-7; R = -Pr
R)-[D2]-17; R = PhCH2
0.0119 ppm
0.0120 ppm
0.0430 ppm
(
S
R
i
3
4
5
(
S
R
(
S
)-[D2]-20; R = 4-TBDMSOC6H4
0.0100 ppm
0.0138 ppm
0.175 ppm
0.183 ppm
(R
)-21 + (
S
)-[D2]-21; R = 4-HOC6H4
Scheme 9. Isotope shifts for oxazolidinones 6, 7, 17, 20 and 21.

3410
E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
(R,S)-syn-[D2]-32 in 87% and 77%, respectively (Scheme
14). The relative levels of mutual recognition were deter-
mined by 1H NMR spectroscopy of the crude reaction mix-
ture, and were shown to be excellent for both
oxazolidinone components; for (R)-6, the mutual recogni-
tion was 96:4 [(S,R)-syn-36: (R,R)-anti-32] and for its
quasi-enantiomeric component, (S)-[D2]-6, was 98:2
{(R,S)-syn-[D2]-32: (S,S)-anti-[D2]-36}. It is interesting to
note that oxazolidinone (R)-6 mutually recognised the
active ester (S)-35 {to give [(S,R)-syn-36]} and its comple-
mentary quasi-enantiomeric D-labelled oxazolidinone
(S)-[D2]-6, recognised the related active ester (R)-28 {to
give (R,S)-syn-[D2]-32} in a near equal fashion.
C6F5OH, DCC
CH2Cl2
Ar
CO2H
Ar
CO2C6F5
H
R
H
R
rac-23-26
rac-27-30
Carboxylic acids
Entry
1
R
Ar
Active esters
Yield
23 (=1)
CH3
92%
72%
65%
75%
Ph
Ph
rac-27 (=8)
rac-28
24
25
26
CH2CH3
2
3
4-CH3C6H4-
4-i-BuC6H4-
rac-29
rac-30
CH3
CH3
4
3. Conclusion
Scheme 11. Synthesis of active esters (rac)-27–30.
In conclusion, we have reported the synthesis of a series of
enantiomerically pure C(5)-di-deuterium-labelled oxazolid-
inones (S)-[D2]-6, (R)-[D2]-7, (R)-[D2]-17, (S)-[D2]-20 and
(S)-[D2]-21 in a good yield. We have also shown that these
oxazolidinones {e.g., (S)-[D2]-6} can be combined with
their non-labelled enantiomer [e.g., (R)-6] to give a quasi-
racemic mixture (R)-6 and (S)-[D2]-6. This combination
of quasi-enantiomeric oxazolidinone isotopomers has addi-
tionally been shown to be a versatile chiral probe for the
discovery of novel parallel kinetic resolutions involving
Evans’ based oxazolidinones.
respectively. In order to ensure that there was no secondary
kinetic isotope effect, these processes were repeated using a
related mutual kinetic resolution protocol, which gave near
identical levels of diastereoselectivity (Scheme 13).
With this information in hand, we next probed the mutual
kinetic separation of an equimolar mixture of quasi-enan-
tiomeric isotopomers (R)-6 and (S)-[D2]-6 using a combina-
tion of quasi-enantiomeric pentafluorophenyl active esters
(R)-28 and (S)-35 (Scheme 14). Deprotonation of the equi-
molar mixture of oxazolidinones, (R)-6 and (S)-[D2]-6, with
n-butyl lithium at ꢁ78 ꢁC in THF, followed by the addition
of the active esters (R)-28 and (S)-35 in THF, gave a sepa-
rable mixture of syn-oxazolidinones (S,R)-syn-36 and
The nearest analogy to this work is that of Vedejs10 with
the parallel kinetic resolution of [12C/13C]-differentially
labelled substrates. In recent years, the use of quasi-enantio-
meric isotopomers as chiral probes for monitoring the
O
O
O
O
O
Ar
Ar
N
O
N
O
HN
O
H
R
R
H
Ph
Ph
Ph
R
( )-6
syn-
A
anti-
A
1.
2.
n
-BuLi
THF, -78 oC
Ar
CO2C6F5
O
O
O
O
O
Ar
H
R
Ar
HN
O
N
O
N
O
(2 equiv.
)
R
H
H
R
(
rac)-27-30
D
D
D
Ph
Ph
Ph
syn-[D2]-B
D
D
D
S
( )-[D2]-6
anti-[D2]-B
Active ester
Ar
Entry
R
anti-A: anti-[D2]-A
syn-A: syn-[D2]-B
Oxazolidinones A
Oxazolidinones B
1
2
3
4
syn-[D2]-31:anti-[D2]-31; 97:3
syn-[D2]-32:anti-[D2]-32; >98:2
syn-[D2]-33:anti-[D2]-33; 95:5
syn-[D2]-34:anti-[D2]-34; 97:3
50:50 ( 2%); 3%
50:50 ( 2%); 1%
51:49 ( 2%); 2%
52:48 ( 2%); 2%
CH3
27 (=8)
Ph
Ph
52:48 ( 2%); 70%
syn-31:anti-31; 97:3
28
29
30
CH2CH3
CH3
syn-32:anti-32; >98:2
syn-33:anti-33; 95:5
syn-34:anti-34; 97:3
50:50 ( 2%); 87%
50:50 ( 2%); 69%
50:50 ( 2%); 79%
4-CH3C6H4-
4-i-BuC6H4-
CH3
Scheme 12. Parallel kinetic resolution of active esters (rac)-27–30 using quasi-enantiomeric isotopomers (R)-6 and (S)-[D2]-6.

E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
3411
O
O
O
O
1. n-BuLi
Ar
Ar
THF, -78 o
C
N
O
N
O
rac-6
H
R
R
H
Ar
CO2C6F5
2.
Ph
Ph
H
R
rac-syn-A
rac-anti-B
rac-27-30
Active ester
Ar
Entry
1
R
anti-A
syn-A
Oxazolidinones
CH3
70%
69%
56%
56%
27
Ph
Ph
2%
1%
2%
1%
syn-31:anti-31; 97:3
syn-32:anti-32; >98:2
syn-33:anti-33; 95:5
syn-34:anti-34; 96:4
CH2CH3
28
29
30
2
3
4
4-CH3C6H4-
4-i-BuC6H4-
CH3
CH3
Scheme 13. Mutual kinetic resolution of active esters (rac)-27–30 using rac-6.
O
O
O
Ph
OC6F5
OC6F5
H
CH3
H
CH3
(S)-35
(R)-28
O
O
O
O
O
Ph
H
N
O
N
O
CH3
H
Ph
CH3 Ph
1.
n
-BuLi
R
( )-6
THF, -78 o
C
)-35
ratio = 96:4
O
(
S,
R
)-syn-36; 87%
(
R
,
R
)-anti-32; 3%
2.
(R
)-28 + (
S
S
( )-[D2]-6
O
O
O
O
Ph
N
O
N
O
H
CH3
H
D
D
D
CH3 Ph
Ph
D
(R,S)-syn-[D2]-32; 77%
ratio = 98:2
(S
,
S
)-anti-[D2]-36; <1%
Scheme 14. Mutual kinetic separation of quasi-enantiomeric isotopomers (R)-6 and (S)-[D2]-6 using two quasi-enantiomeric active esters (R)-28 and (S)-
35.
stereochemical outcome of other related processes has
become increasingly popular.11 Within our laboratory,
we are currently studying these applications, which will
be reported in due course.
Flash column chromatography was carried out using
Merck Kieselgel 60 (230–400 mesh). Thin layer chromato-
graphy (TLC) was carried out on commercially available
pre-coated plates (Merck Kieselgel 60F254 silica). Proton
and carbon NMR spectra were recorded on a Bruker
250 MHz and 400 MHz Fourier transform spectrometers
using an internal deuterium lock. Chemical shifts are
quoted in parts per million downfield from tetramethyl-
silane. Carbon NMR spectra were recorded with broad
proton decoupling. Infrared spectra were recorded on a
Shimadzu 8300 FTIR spectrometer. Optical rotations12
were measured using an automatic AA-10 Optical Activity
4. Experimental
4.1. General
All solvents were distilled before use. All reactions were
carried out under nitrogen using oven-dried glassware.

3412
E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
Ltd polarimeter. The levels of D-incorporation were deter-
mined by a combination of mass, proton and carbon NMR
spectra. All isotopically labelled derivatives have been
given an L superscript and unlabelled derivatives a
U superscript.
4.4. Equimolar mixture of 4-phenyl-5,5-dideuterio-oxazolid-
inone (S)-[D2]-6 and 4-phenyl-oxazolidinone (R)-6
An equimolar mixture of each adduct (ꢀ10 mg) was added
to dichloromethane (5 ml). The solution was evaporated to
give the above equimolar mixture of quasi-enantiomeric
isotopomers.
4.2. Dideuterio-phenylglycinol (S)-[D2]-14
Melting point: (S)-[D2]-6; (R)-6 = 121-124 ꢁC {for rac-6 =
130–132 ꢁC; lit.16 137–139 ꢁC}.
Lithium aluminium deuteride (5.31 g, 126.6 mmol) was
slowly added to THF (150 ml). The resulting solution
was cooled to 0 ꢁC using an ice bath. L-Phenylglycine
(S)-11 (12.23 g, 80.9 mmol) was then slowly added 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 ether (3 · 150 ml) and the organic filtrates
were dried over MgSO4, and concentrated under reduced
pressure to give dideuterio phenylglycinol (S)-[D2]-14
dH (400 MHz; CDCl3) 7.41-7.31 (10H, m, 10 · CH; PhU
and PhL), 6.43 (2H, s, NHU and NHL), 4.94 (1H, dd, J
8.6 and 6.9, CHNU), 4.93 (1H, s, CHNL), 4.72 (1H, t, J
8.6, CHAHBOU) and 4.17 (1H, dd, J 8.6 and 6.9, CHA
HBOU); dC (100 MHz; CDCl3) 159.9 (2 · C@OU and
C@OL), 139.4 (2 · i-C; PhU and PhL), 129.1,4 128.72 and
125.94 (10 · CH; Ph), 72.6 (CH2OU), 72.1 (1C, quintet,
1JC, D = 23.8, CD2OL), 56.3 (CHNU) and 56.1 (CHNL).
By mass spectrometry, this mixture of oxazolidinones (S)-
[D2]-6 and (R)-6 gave a 52:48 ratio of (S)-[D2]-6:(R)-6;
for (S)-[D2]-6; found MNH4þ, 183.1097; C9H11D2N2O2 rþe-
quires MNH4þ, 183.1097, and for (R)-6; found MNH4
,
(8.89 g, 79%) as a white powder; mp = 77–79 ꢁC (unla-
181.0970; C9H13N2O2 requires MNH4þ, 181.0972; and IR
20
belled lit.13 76.5–78.5 ꢁC); ½aꢂD ¼ þ33:0 (c 0.9, 1 M HCl);
spectroscopy, mmax (CH2Cl2)/cmꢁ1 2305 (br, C–D) and
20
20
lit.14 ½aꢂD ¼ þ32 (c 0.75, 1 M HCl); mmax (CHCl3)/cmꢁ1
1760 (C@O); {½aꢂD ¼ꢀ 0:0 (c 1.0, DMSO)}.
3270 (NH), 3042 (OH), 2255 (CD) and 2134 (CD); dH
(400 MHz; CDCl3) 7.35–7.24 (5H, m, 5 · CH; Ph), 4.00
(1H, s, CHN) and 2.90–2.40 (3H, br s, OH and 2 · NH);
dC (100 MHz; CDCl3) 142.4 (i-C; Ph), 128.5,2 127.41 and
Isotopic shifts by NMR spectroscopy. Proton NMR spec-
troscopy: negative isotope shift at 4.93 ppm (CHN) is
0.0119 ppm (4.78 Hz at 400 MHz). Carbon NMR spectro-
scopy shifts: (a) negative isotopic shift at 72.6 ppm (CH2O)
was 0.4278 ppm (43 Hz at 100.6 MHz); (b) negative isoto-
pic shift at 56.3 ppm (CHN) was 0.175 ppm (17.6 Hz at
100.6 MHz).
1
126.42 (5 · CH; Ph), 67.2 (1C, quintet, JC,D = 22.1 Hz,
CD2) and 57.1 (CHN) (found MH+, 140.1039;
C8H10D2NO requires 140.1039).
4.3. 4-Phenyl-5,5-dideuterio-oxazolidinone (S)-[D2]-6
4.5. Dideuteriovalinol (R)-[D2]-15
Anhydrous potassium carbonate (0.88 g, 6.3 mmol) was
added to a solution of dideuteriophenylglycinol (S)-[D2]-
14 (8.49 g, 61 mmol) and diethyl carbonate (15.32 g,
15.8 ml, 129.8 mol). 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 extracted
with dichloromethane (2 · 50 ml). The combined organic
layers were dried over MgSO4 and evaporated under re-
duced pressure to give crude oxazolidinone (S)-[D2]-6. This
residue was recrystallised from a mixture of hot petroleum
ether (40–60 ꢁC)/ethyl acetate (1:2) to give 4-phenyl-
5,5-dideuterio-oxazolidinone (S)-[D2]-6 (4.02 g, 40%) as
In the same way as amino alcohol (S)-[D2]-14, D-valine (R)-
12 (10.5 g, 89.5 mmol) and lithium aluminium deuteride
(5.09 g, 121.3 mol) in THF (150 ml) gave (R)-dideuterio-
valinol (R)-[D2]-15 (7.20 g, 77%) as a white powder;
20
mp = 29–31 ꢁC (unlabelled lit.17 39–40 ꢁC); ½aꢂD ¼ ꢁ13:4
20
(c 2.4, CHCl3)]; [lit.17 unlabelled ½aꢂD ¼ ꢁ14:0 (c 9.9, etha-
nol)]; mmax (CHCl3)/cmꢁ1 3375 (NH), 3054 (NH), 2965
(OH), 2305 (CD) and 2256 (CD); dH (400 MHz; CDCl3)
3.10–2.70 (3H, m, OH and NH2), 2.50 (1H, br d, J 6.2,
CHN), 1.54 (1H, broad septet, J ꢀ 6.7, CH(CH3)2), 0.86
(3H, d,
J
J
6.8, ACH3CHBCH3) and 0.84 (3H, d,
6.8, ACH3CHBCH3); dC (100 MHz; CDCl3) 63.7
1
(1C, quintet, JC,D = 23.1, CD2O), 58.1 (CHN), 30.8
(CH(CH3)2), 19.1 (CH3) and 18.3 (CH3); m/z 105.9
(100%, M+).
white crystals; mp = 124–127 ꢁC (unlabelled (S)-; lit.15
20
132–133 ꢁC); Rf [ethyl acetate/ethanol (9:1)] 0.71; ½aꢂD
¼
þ48:4 (c 1.01, CHCl3), unlabelled (S)-; lit.15
20
½aꢂD ¼ þ49:5 (c 2.1,CHCl3); mmax (CHCl3)/cmꢁ1 3270
4.6. 4-Isopropyl-5,5-dideuterio-oxazolidinone (R)-[D2]-7
(NH), 2256 (CD), 2140 (CD) and 1748 (C@O); dH
(400 MHz; CDCl3) 7.37–7.25 (5H, m, 5 · CH; Ph), 5.95–
5.84 (1H, br s, NH) and 4.97 (1H, s, CHN); dC
(100 MHz; CDCl3) 159.7 (C@O), 139.6 (i-C; Ph), 129.2,2
128.91 and 126.12 (5 · CH; Ph), 71.9 (1C, quintet,
1JC,D = 23.3 Hz CD2) and 56.2 (CHN) (found
In the same way as oxazolidinone (S)-[D2]-6, dideuterio-
valinol (R)-[D2]-15 (6.99 g, 66.47 mmol), potassium car-
bonate (0.92 g, 6.64 mmol) and diethylcarbonate (16.49 g,
16.91 ml, 139.66 mmol) gave dideuteriooxazolidinone (R)-
[D2]-7 (4.93 g, 57%) as a white powder. This was recrystal-
lised from a mixture of hot petroleum ether (40–60 ꢁC)/
ethyl acetate (ratio: 1:2) to give white crystal; mp = 60–
þ
þ
,
MNH4
,
183.1097; C9H11D2N2O2 requires MNH4
183.1097).

E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
3413
62 ꢁC (unlabelled (S)-; lit.18 70–72 ꢁC); Rf [ethyl acetate/
(400 MHz; CDCl3) 7.38–7.17 (5H, m, 5 · CH; Ph), 3.10
(1H, dd, J 8.6 and 5.2, CHN), 2.78 (1H, dd, J 13.4 and
5.2, CHAHBPh), 2.51 (1H, dd, J 13.4 and 8.6, CHAHBPh)
and 2.34–1.98 (3H, br s, OH and 2 · NH); dC (100 MHz;
CDCl3) 138.6 (i-C; Ph), 129.1,2 128.52 and 126.31
20
ethanol (9:1)] 0.66; ½aꢂD20¼ þ16:6 (c 5.2, CHCl3); (unla-
belled (S)- lit.19 ½aꢂD ¼ ꢁ16:5 (c 6.0, ethanol));
mmax (CHCl3)/cmꢁ1 3265 (NH), 2306 (CD), 2254 (CD)
and 1752 (C@O); dH (400 MHz; CDCl3) 7.10–6.90 (1H,
br s, NH), 3.45 (1H, d, J 6.7, CHN), 1.69 (1H, m,
CH(CH3)2), 0.87 (3H, d, J 6.8, ACH3CHBCH3) and 0.82
(3H, d, J 6.8, ACH3CHBCH3); dC (100 MHz; CDCl3) 166
1
(5 · CH; Ph), 65.3 (1C, quintet, JC,D = 21.5 Hz, CD2O),
53.9 (CHN) and 40.7 (CH2Ph); m/z 153.9 (100%, M+).
4.9. 4-Benzyl-5,5-dideuterio-oxazolidinone (R)-[D2]-17
1
(OC@O), 67.8 (1C, quintet, JC, D = 24.4, CD2O), 58.1
(CHN), 32.5 (CH(CH3)2), 17.8 (CH3) and 17.5 (CH3)
(found MH+, 132.0990; C6H10D2NO2 requires 132.0988).
In the same way as oxazolidinone (S)-[D2]-6, dideuterio-
phenylglycinol (R)-[D2]-16 (8.41 g, 54.8 mmol), potassium
carbonate (0.82 g, 6.0 mmol) and diethylcarbonate
(13.79 g, 14.15 ml, 0.12 mol) gave (R)-dideuterio-oxazolid-
inone (R)-[D2]-17 (3.88 g, 40%) as a white powder. This
was recrystallised from a mixture of hot petroleum ether
(40–60 ꢁC)/ethyl acetate (1:2) to give white crystal;
4.7. Equimolar mixture of 4-isopropyl-5,5-dideuterio-oxa-
zolidinone (R)-[D2]-7 and 4-isopropyl-oxazolidinone (S)-7
An equimolar mixture of each adduct (ꢀ10 mg) was added
to dichloromethane (5 ml). The solution was evaporated to
give the above equimolar mixture of quasi-enantiomeric
isotopomers.
mp = 70–73 ꢁC (lit.22 87–88.5 ꢁC unlabelled); Rf [ethyl ace-
20
tate/ethanol (9:1)] 0.71; ½aꢂD ¼ þ53:7 (c 1.03, CHCl3);
20
(unlabelled lit.23 ½aꢂD ¼ ꢁ62:0 (c 1.0, CHCl3)); mmax
Melting point: (R)-[D2]-7; (S)-7 = 77–78 ꢁC; {rac-7 = 73–
75 ꢁC; lit.20 75 ꢁC}.
(CHCl3)/cmꢁ1 3272 (NH), 2305 (CD), 2255 (CD) and
1755 (C@O); dH (400 MHz; CDCl3) 7.34–7.23 (3H, m,
3 · CH; Ph), 7.18–7.06 (2H, m, 2 · CH; Ph), 5.47 (1H, br
s, NH), 4.07 (1H, t, J 7.0, CHN) and 2.87 (2H, d, J 7.0,
CH2Ph); dC (100 MHz; CDCl3) 159.4 (C@O), 135.9 (i-C;
Ph), 129.1,2 128.92 and 127.31 (5 · CH; Ph), 69.5 (1C, quin-
dH (400 MHz; CDCl3) 7.20–7.05 (2H, br s, NHU and
NHL), 4.37 (1H, t, J 8.8, CHAHBOU), 4.02 (1H, dd, J 8.8
and 6.4, CHAHBOU), 3.55 (1H, br, CHNU), 3.52 (1H, d,
U
2
J 7.8, CHNL), 1.65 (2H, br octet, J ꢀ 6.7, CHðCH3Þ
tet, JC,D = 22.6 Hz, CD2O), 53.6 (CHN) and 41.4
1
L
and CHðCH3Þ2 ), 0.89 (6H, d, J6.8, ACH3CHBCH3U and ACH3-
(CH2Ph) (found MNa+, 202.0806; C10H9D2NO2Na re-
quires 202.0808).
CHBCHU3 ) and 0.82 (6H, d, J 6.8, ACH3CHBCHU
3
and ACH3CHBCH3U); dC (100 MHz; CDCl3) 160.6 (OC@
OU and OC@OL), 68.5 (CH2OL), 67.8 (1C, quintet,
1JC,D = 23.1, CD2OL), 58.3 (CHNU), 58.1 (CHNL), 32.6
4.10. Equimolar mixture of 4-benzyl-5,5-dideuterio-oxazol-
idinone (R)-[D2]-17 and 4-benzyl-oxazolidinone (R)-17
U
L
(CHðCH3Þ ), 32.5 ðCHðCH3Þ Þ, 17.8 (CHU and CH3L)
2
2
3
and 17.6 (CHU3 and CHL3 ). By mass spectrometry, this mix-
The solution was evaporated to give the above equimolar
mixture of quasi-enantiomeric isotopomers. Melting point:
(R)-[D2]-17; (S)-17 = 53–65 ꢁC; {(rac)-17 = 65–67 ꢁC; lit.24
72–74 ꢁC}. dH (400 MHz; CDCl3) 7.34–7.23 (6H, m,
6 · CH; PhU and PhL), 7.18–7.06 (4H, m, 4 · CH; PhU
and PhL), 5.47 (2H, br s, NHU and NHL), 4.45 (1H, dd,
J 8.4 and 8.1, CHAHBOU), 4.15 (1H, dd, J 8.4 and 5.7,
CHAHBOU), and 4.12–4.05 (1H, m, CHNU), 4.10 (1H, t,
J 7.1, CHNL) and 2.87 (4H, d, J 7.0, CH2PhU and
CH2PhL); dC (100 MHz; CDCl3) 159.9 (C@OU and
C@OL), 135.9 (2 · i-C; PhU and PhL), 130.0,4 128.94 and
127.32 (10 · CH; PhU and PhL), 69.6 (1C, CH2OU), 69.5
ture of oxazolidinones (R)-[D2]-7 and (S)-7 gave a 49:51
þ
ratio of (R)-[D2]-7:(S)-7; for (R)-[D2]-7; found MNH4
,
149.1255; C6H13D2N2O2 requires MNH4þ, 149.1254, and
for (R)-7; found MNH4þ, 147.1129; C9H15N2O2 requires
MNH4þ, 147.1128; and IR spectroscopy, mmax (CH2Cl2)/
cmꢁ1 2305 (C–D) and 2253 (C–D) and 1752 (C@O);
20
{½aꢂD ¼ þ0:4 (c 20.0, CHCl3)}.
Isotopic shifts by NMR spectroscopy. Proton NMR spec-
troscopy shifts: negative isotope shift at 3.55 ppm (CHN) is
0.012 ppm (4.86 Hz at 400 MHz). Carbon NMR spectro-
scopy shifts: (a) negative isotopic shift at 68.5 ppm
(CH2O) was 0.649 ppm (65.3 Hz at 100.6 MHz); (b) nega-
tive isotopic shift at 58.3 ppm (CHN) was 0.191 ppm
(19.2 Hz at 100.6 MHz); (c) negative isotopic shift at
32.5 ppm (CH2(CH3)2) was 0.053 ppm (5.4 Hz at
100.6 MHz).
1
(1C, quintet, JC,D = 22.4 Hz, CD2OL), 53.7 (CHNU),
53.6 (CHNL), 41.4 (CH2PhU) and 41.3 (CH2PhL). By mass
spectrometry, this mixture of oxazolidinones (R)-[D2]-17
and (S)-17 gave a 48:52 ratio of (R)-[D2]-12:(S)-12; for
(R)-[D2]-12; found MNH4þ, 197.1254; C10H13D2N2O2
þ
requireþs MNH4
,
197.1254, and for (S)-12; found
þ
MNH4
,
195.1128; C10H15N2O2 requires MNH4
,
4.8. Dideuterio-phenylalaninol (R)-[D2]-16
195.1128; and IR spectroscopy, mmax (CH2Cl2)/cmꢁ1 2358
20
(CD), 2341 (CD) and 1755 (C@O); {½aꢂD ¼ꢀ 0:0 (c 1.0,
In the same way as amino alcohol (S)-[D2]-14, D-phenylal-
anine (R)-13 (9.50 g, 57.5 mmol) and lithium aluminium
deuteride (3.66 g, 87.2 mmol) in THF (150 ml) gave dideu-
DMSO)}.
Isotopic shifts by NMR spectroscopy. Proton NMR spec-
troscopy shifts: negative isotope shift at 4.10 ppm (CHN) is
0.0043 ppm (1.64 Hz at 400 MHz). Carbon NMR spectro-
scopy shifts: (a) negative isotopic shift at 69.6 ppm (CH2O)
was 0.067 ppm (67.4 Hz at 100.6 MHz); (b) negative iso-
topic shift at 53.7 ppm (CHN) was 0.183 ppm (18.4 Hz at
terio-phenylalaninol (R)-[D2]-16 (8.19 g, 93%) as a white
20
powder; mp = 82–85 ꢁC (lit.21 88–90 ꢁC); ½aꢂD ¼ þ26:4
20
(c 1, 1 M HCl); lit.14 ½aꢂD ¼ þ23:0 (c 1.2, HCl/H2O); mmax
(CHCl3)/cmꢁ1 3361 (NH and OH), 2920 (NH and OH);
2853 (NH and OH), 2411 (CD) and 2305.2 (CD); dH

3414
E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
100.6 MHz); (c) negative isotopic shift at 41.4 ppm
(CH2Ph) was 0.045 ppm (4.6 Hz at 100.6 MHz).
316.1339); and oxazolidinone (S)-[D2]-21 (0.21 g, 11%) as
a white powder; mp= 193–195 ꢁC {(R)-unlabelled: 190–
20
192 ꢁC}; ½aꢂD ¼ þ21:6 (c 2.2, DMSO); {(R)-unlabelled:
20
4.11. N-tert-Butoxycarbonyl-(4-tert-butyldimethylsilyoxy-
phenyl)-dideuterioglycinol (S)-[D2]-19
½aꢂD ¼ ꢁ36:6 (c 3.2, DMSO)}; mmax (CHCl3)/cmꢁ1 3600–
3200 (OH), 2255 (CD), 2221 (CD) and 1754 (C@O); dH
(400 MHz; [d6]-DMSO) 9.41 (1H, s, OH), 7.96 (1H, s,
NH), 7.05 (2H, dt, J 8.5 and 2.5, 2 · CH; Ar), 6.88 (2H,
dt, J 8.5 and 2.5, 2 · CH; Ar), 4.77 (1H, s, CHN); dC
(100 MHz; [d6]-DMSO) 158.6 (OC@O), 157.7 (i-CO; Ar),
131.0 (i-C; Ar), 127.32 and 115.32 (4 · CH; Ar), 70.9 (1C,
Lithium aluminium deuteride (1.53 g, 36.5 mmol) was
slowly added to a stirred solution of ester (S)-18 (5.01 g,
20
12.8 mmol) {½aꢂD ¼ þ68:7 (c 12.7, CH2Cl2)} in ether
(50 ml) at 0 ꢁC. The resulting solution was stirred for 3 h.
Ammonium chloride (50 ml) was slowly added, and the
resulting solution was extracted with ether (3 · 100 ml).
The combined organic layers were dried (over MgSO4)
1
quintet, JC,D = 23.8Hz, CD2O) and 54. (CHN) (found
MH+, 199.1045; C9H8D2NO3 requires 199.1046) (unla-
belled (S)-21: found MNH4þ, 197.0919; C9H13N2O3 re-
quires 197.0921; and unlabelled (R)-21: found M+,
179.0578; C9H9NO3 requires 179.0577).
and evaporated under reduced pressure to give the dideute-
20
rio-alcohol (S)-[D2]-19 (4.46 g, 94%) as an oil; ½aꢂD
¼
20
þ20:0 (c 38.5, CH2Cl2) [unlabelled (S)-19 ½aꢂD ¼ þ25:9
(c 31.5, CH2Cl2)]; mmax (CHCl3)/cmꢁ1 2305 (CD)
and 1694 (C@O) (NH); dH (400 MHz; CDCl3) 7.04
(2H, dd, J 8.6 and 2.9, 2 · CH; Ar), 6.72 (2H, dd, J 8.6
and 2.9, 2 · CH; Ar), 5.20 (1H, br s, NH), 4.59 (1H, br s,
OH), 3.60 (1H, br s, CHN), 1.39–1.34 (9H, br s, t-BuO),
0.89 (9H, s, t-BuSi), 0.10 (6H, s, 2 · CH3Si); dC
(100 MHz; CDCl3) 156.3 (i-CO; Ar), 155.0 (C@O), 132.0
(i-C; Ar), 127.6 (2 · CH; Ar); 120.4 (2 · CH; Ar), 79.9
(CO; t-BuO), 65.5 (1C, multiplet, CD2O), 56.1 (CHN),
28.3 (3 · Me; t-BuO), 25.6 (3 · Me; t-BuSi) and ꢁ4.5
(2 · Me, SiMe2) (found MH+, 370.2381; C19H32D2NO4
requires 370.2381; unlabelled—found MH+, 368.2251;
C19H33NO4Si requires 368.2252).
4.13. Equimolar mixture of 4-(4-tert-butyldimethylsilyoxy-
phenyl)-5,5-dideuterio-oxazolidin-2-one (S)-[D2]-20 and 4-
(4-tert-butyldimethylsilyoxyphenyl)-oxazolidin-2-one (R)-20
The solution was evaporated to give the above equimolar
mixture of quasi-enantiomeric isotopomers. Melting point:
(S)-[D2]-20; (R)-20 = 110–112 ꢁC. dH (400 MHz; CDCl3)
7.12 (4H, dt, J 8.4 and 4.8, 4 · CH; ArU and ArL), 6.76
(4H, dt, J 8.4 and 4.8, 4 · CH; ArU and ArL), 6.30 (2H,
br s, NHU and NHU), 4.82 (1H, t, J 8.6, CHNU), 4.81
(1H, s, CHNL), 4.60 (1H, t, J 8.6, CHAHBOU), 4.07 (1H,
dd, J 8.6 and 7.4, CHAHBOL), 0.92 (18H, s, 3 · CH3; t-
BuU and t-BuL) and 0.13 (12H, s, 2 · CH3; SiCHU and
3
SiCHL); dC (100 MHz; CDCl3) 160.2 (C@OU and C@OL),
3
4.12. 4-(4-tert-Butyldimethylsilyoxyphenyl)-5,5-dideuterio-
oxazolidin-2-one (S)-[D2]-20 and 4-(4-hydroxyphenyl)-5,5-
dideuterio-oxazolidin-2-one (S)-[D2]-21
156.2 (i-CO; ArU and ArL), 132.3 (i-C; ArU), 132.2 (i-C;
ArL), 127.44 and 120.64 (8 · CH; ArU and ArL), 72.9
1
(1H, s, CH2OU), 72.2 (1C, quintet, JC, D = 20.7 Hz,
CD2OL), 56.1 (CHNU), 55.9 (CHNL), 25.8 (6 · CH3;
Thionyl chloride (11.4 g, 7.0 ml, 95.9 mmol) was added to
dideuterio-glycinol (S)-[D2]-19 (4.36 g, 11.8 mmol). The
resulting solution was stirred for 12 h. The remaining thio-
nyl chloride was removed through distillation, and the
residual thionyl chloride was removed under reduced pres-
sure. The resulting residue was dissolved in ethyl acetate
(20 ml) and sequentially washed with water, NaHCO3 (sat-
urated) and brine, dried over MgSO4 and concentrated
under reduced pressure. Dichloromethane (50 ml) was added,
and the insoluble oxazolidinone (S)-[D2]-21 (0.21 g, 11%)
was removed through filtration. The filtrate was concen-
trated under reduced pressure, and recrystallised in hot
ethyl acetate to give oxazolidinone (S)-[D2]-20 (1.52 g,
t-BuU and t-BuL) and ꢁ4.3 (4 · CH3; 4 ꢃ SiCHU and
3
SiCHL3 ) (found MUNH4
,
311.1786; C15H27N2O3Si
þ
requires 311.1785; and found MLNH4
,
313.1910;
þ
C15H25D2N2O3Si requires 313.1911); mmax (DMSO)/cmꢁ1
20
2265 (CD), 2221 (CD) and 1755 (C@O); {½aꢂD ¼ꢀ 0:0 (c
1.7, DMSO)}. Isotopic shifts by NMR spectroscopy. Pro-
ton NMR spectroscopy shifts: negative isotope shift at
4.81 ppm (CHN) is 0.0105 ppm (4.20 Hz at 400 MHz).
Carbon NMR spectroscopy shifts: (a) negative isotopic
shift at 132.2 ppm (i-C; Ar) was 0.0115 ppm (1.2 Hz at
100.6 MHz); (b) negative isotopic shift at 72.6 ppm
(CH2O) was 0.634 ppm (63.7 Hz at 100.6 MHz); (c) nega-
tive isotopic shift at 55.9 ppm (CHN) was 0.175 ppm
(17.5 Hz at 100.6 MHz).
45%) as a white powder; mp = 132–133 ꢁC {for (R)-:
20
132–135 ꢁC; lit.8 (R)-unlabelled 142–142.5 ꢁC}; ½aꢂD
¼
20
þ34:4 (c 3.1, DMSO), {for (R)-: ½aꢂD ¼ ꢁ37:2 (c 1.28,
4.14. Equimolar mixture of 4-(4-hydroxyphenyl)-5,5-dideu-
terio-oxazolidin-2-one (S)-[D2]-21 and 4-(4-hydroxyphenyl)-
oxazolidin-2-one (R)-21
20
DMSO); lit.8 (R)-unlabelled ½aꢂD ¼ ꢁ37:6 (c 1.05, THF)};
mmax (CHCl3)/cmꢁ1 2264 (CD), 2221 (CD) and 1750
(C@O); dH (400 MHz; CDCl3) 7.15 (2H, dt, J 8.4 and
4.8, 2 · CH; Ar), 6.79 (2H, dt, J 8.4 and 4.8, 2 · CH;
Ar), 5.90 (1H, br s, NH), 4.83 (1H, s, CHN), 0.93 (9H, s,
3 · CH3; t-Bu) and 0.15 (6H, s, 2 · CH3; SiCH3); dC
(100 MHz; CDCl3) 159.7 (C@O), 156.1 (i-CO; Ar), 131.8
(i-C; Ar), 127.22 and 120.62 (2 · CH; Ar), 72.0 (1C, quintet,
1JC,D = 23.1 Hz, CD2O), 55.8 (CHN), 25.6 (3 · CH3; t-Bu)
and ꢁ4.4 (2 · CH3; 2 · SiCH3) (found M+, 295.1562;
C15H21D2NO3Si+ requires 295.1567) (unlabelled (S)-20:
found MNa+, 316.1342; C15H23NO3SiNa requires
The solution was evaporated to give the above equimolar
mixture of quasi-enantiomeric isotopomers. Melting point:
(S)-[D2]-21; (R)-21 = 140-145 ꢁC. dH (400 MHz; [d6]-
DMSO) 9.55 (2H, s, OHU and OHL), 8.09 (2H, s, NHU and
NHL), 7.17 (4H, dt, J 8.4 and 4.8, 4 · CH; ArU and
ArL), 6.80 (4H, dt, J 8.4 and 4.8, 4 · CH; ArU and ArL),
4.85 (1H, br t, J 8.2 ꢀ 7.3, CHNU), 4.80 (1H, s, CHNL),
4.63 (1H, t, J 8.4, CHAHBOU) and 3.98 (1H, dd, J 8.4
and 6.6, CHAHBOU); dC (100 MHz; [d6]-DMSO) 158.9

E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
3415
(OC@OU and C@OL), 157.2 (i-CO; ArL and ArU), 131.0 (i-
C; Ar, ArL and ArU), 127.44 and 115.54 (8 · CH; ArL and
ArU), 71.6 (CH2OU) and 70.9 (1C, quintet,
1JC,D = 21.5 Hz, CD2OL), 54.8 (CHNU) and 54.6 (CHNL).
(found MU+, 179.0574; C9H9NO3 requires 179.0577; and
found ML+, 181.0700; C9H7D2NO3 requires 181.0702);
THF (5 ml), gave oxazolidinone (R)-22 (0.17 g, 50%) as a
white powder; Rf [diethyl ether/petroleum ether (1:1)]
20
0.69; mp = 180–183 ꢁC; {lit.25 187–188 ꢁC} ½aꢂD ¼ ꢁ91:8
(c 0.73, CHCl3) {lit.25 ꢁ75.9 (c 0.94, ethyl acetate)}; mmax
(CHCl3)/cmꢁ1 1769 (C@O) and 1697 (C@O); dH
(400 MHz; CDCl3) 7.64 (2H, dd, J 8.2 and 2.1, 2 · CH;
C(2)–PhCO); 7.48 (1H, tt, J 7.5 and 1.2, 1 · CH; C(4)–
PhCO), 7.38–7.26 (7H, m, 7 · CH; Ph and PhCO), 5.57
(1H, dd, J 8.8 and 7.2, CHN), 4.71 (1H, t, J 8.8, CHAHBO),
4.25 (1H, t, J 8.8 and 7.2, CHAHBO), dC (100 MHz;
CDCl3) 169.2 (NC@O), 153.8 (OC@O), 137.6 (i-C; Ph),
132.8 (i-C; Ph), 132.7,1 129.3,2 129.2,2 128.9,1 127.92 and
126.32 (10 · CH; 2 · Ph), 69.8 (CH2O) and 58.7 (CHN)
mmax (DMSO)/cmꢁ1 2265 (CD), 2221 (CD) and 1752
20
(C@O); {½aꢂD ¼ꢀ 0:0 (c 0.45, DMSO)}. Proton NMR
spectroscopy shifts: negative isotope shift at 4.85 ppm
(CHN) is 0.0138 ppm (5.52 Hz at 400 MHz). Carbon
NMR spectroscopy shifts: (a) negative isotopic shift at
71.6 ppm (CH2O) was 0.680 ppm (68.4 Hz at
100.6 MHz); (c) negative isotopic shift at 55.8 ppm
(CHN) was 0.183 ppm (18.4 Hz at 100.6 MHz).
þ
þ
(found MNH4
285.1234).
,
285.1236; C16H17N2O3
requires
4.15. 4-Phenyl-5,5-dideuterio-3-benzoyl oxazolidin-2-one
(S)-[D2]-22 and 4-phenyl-3-benzoyl-oxazolidin-2-one (R)-22
4.17. 4-Phenyl-5,5-dideuterio-3-benzoyl oxazolidin-2-one
(S)-[D2]-22
n-BuLi (0.55 ml, 2.5 M in hexane, 1.36 mmol) was added to
a stirred solution of oxazolidinone (R)-6 (0.1 g, 0.62 mmol)
and (S)-[D2]-6 (0.1 g, 0.62 mmol) in THF at ꢁ78 ꢁC. After
stirring for 1 h, a solution of benzoyl chloride (0.21 g,
1.48 mmol) in THF (5 ml) was added. The resulting mix-
ture was stirred for 2 h at ꢁ78 ꢁC. The reaction was
quenched with water (10 ml). The organic layer was ex-
tracted with diethyl ether (2 · 10 ml), dried over MgSO4
and evaporated under reduced pressure. The residue was
purified by flash column chromatography on silica gel elut-
ing with light petroleum (bp 40–60 ꢁC)/diethyl ether (1:1)
to give an inseparable mixture of oxazolidinones (R)-22
and (S)-[D2]-22 (0.142 g, 43%) as a white solid; Rf [diethyl
In the same way as oxazolidinone 22, n-BuLi (0.56 ml,
2.5 M in hexane, 1.4 mmol), oxazolidinone (S)-[D2]-6
(0.21 g, 1.28 mmol) and benzoyl chloride (0.22 g,
1.54 mmol) in THF (5 ml), gave the oxazolidinone (S)-
[D2]-22 (0.21 g, 61%) as a white solid; Rf [diethyl ether/
petroleum ether (1:1)] 0.69; mp = 180–182 ꢁC {lit.25 unla-
20
belled 187–188 ꢁC}; ½aꢂD ¼ þ77:7 (c 0.4, CHCl3); mmax
(CHCl3)/cmꢁ1 2410 (CD), 2305 (CD), 1786 (C@O) and
1692 (C@O); dH (400 MHz; CDCl3) 7.64 (2H, dd, J 8.2
and 1.2, 2 · CH; C(2)–PhCO); 7.48 (1H, tt, J 7.5 and 1.2,
1 · CH; C(4)–PhCO), 7.42–7.24 (7H, m, 7 · CH; Ph and
PhCO) and 5.57 (1H, s, CHN); dC (100 MHz; CDCl3)
169.2 (NC@O), 153.6 (OC@O), 137.6 (i-C; Ph), 132.8 (i-
C; Ph), 132.7,1 129.3,2 129.2,2 128.9,1 127.92 and 126.32
ether/petroleum ether (1:1)] 0.69; mp = 175–176 ꢁC (unla-
20
belled (rac)-22; mp = 174–176 ꢁC); ½aꢂD ¼ꢀ 0:0 (c 1.0,
CHCl3); mmax (CHCl3)/cmꢁ1 2410 (CD), 2305 (CD), 1768
(C@O) and 1695 (C@O); dH (400 MHz; CDCl3) 7.64 (4H,
dd, J 8.2 and 2.1, 4 · CH; C(2)–PhCOU and C(2)–PhCOL);
7.47 (2H, tt, J 7.5 and 1.2, 2 · CH; C(4)–PhCOU and C(4)–
PhCOU), 7.38–7.27 (14H, m, 14 · CH; PhU, PhL, PhCOU
and PhCOL), 5.57 (1H, dd, J 8.8 and 7.3, CHNU), 5.56
(1H, s, CHNL), 4.71 (2H, t, J 8.8, CHAHBOU), 4.26 (1H,
t, J 8.8 and 7.2, CHAHBOU); dC (100 MHz; CDCl3) 169.2
(NC@OU and NC@OL), 153.6 (OC@OU and OC@OL),
137.6 (i-C; PhU and PhL), 132.8 (i-C; Ph), 132.7,1 129.3,2
129.2,2 128.9,1 127.92 and 126.32 (20 · CH; 2 · PhU and
(10 · CH; 2 · Ph), 69.8 (1C, quintet, JC,D = 23.0 Hz;
1
CD2O) and 58.5 (CHN) (found MNH4þ, 287.1364;
þ
C16H15D2N2O3 requires 287.1359).
4.18. ( )-Pentafluorophenyl 2-phenylpropionate rac-27
2-Phenylpropionic acid rac-23 (5.00 g, 33.32 mmol) was
added to a stirred solution of N,N0-dicyclohexylcarbodii-
mide (DCC) (7.58 g, 36.73 mmol) in dichloromethane
(20 ml) and stirred for 10 min. A solution of pentafluor-
ophenol (6.15 g, 33.43 mmol) in dichloromethane (20 ml)
was slowly added, and the resulting solution was stirred
for 12 h. The resulting precipitate (N,N0-dicyclohexylurea)
was filtered off (using suction filtration). Water (30 ml)
was added and the solution was extracted with dichloro-
methane (3 · 50 ml) and dried (over MgSO4). The com-
bined organic layers were evaporated under reduced
pressure. The crude residue was purified by flash column
chromatography on silica gel eluting with light petroleum
(40–60 ꢁC)/diethyl ether (9:1) to give pentafluorophenyl
2-phenylpropionate rac-27 (9.71 g, 92%) as a white nee-
dle-like solid; Rf [light petroleum (40–60 ꢁC)/diethyl ether
(9:1)] 0.63; mp 27–28 ꢁC; mmax (film)/cmꢁ1 1784 (C@O);
dH (270 MHz; CDCl3) 7.41–7.28 (5H, m, 5 · CH; Ph),
4.07 (1H, q, J 7.2, CH3CH) and 1.64 (3H, d, J 7.2,
CH3CH); dC (100 MHz; CDCl3) 170.6 (OC@O), 141.1
2 · PhL),
69.8
(CH2OU),
69.2
(1C,
quintet,
1JC,D = 23.0 Hz, CD2OL), 58.7 (CHNU) and 58.6 (CHNL).
Isotopic shifts by NMR spectroscopy. Proton NMR shifts:
negative Isotopic shift at 5.57 ppm was 0.0110 ppm (4.4 Hz
at 400 MHz). Carbon NMR shifts: (a) negative isotopic
shift at 69.8 ppm (CD2O) was 0.5276 ppm (53.0 Hz at
100.6 MHz); (b) negative isotopic shift at 58.7 ppm
(CHN) was 0.1759 ppm (17.6 Hz at 100.6 MHz). (found
MUNH4þ, 285.1þ235; C16H17N2O3 requires 285.1234; and
þ
found MLNH4
287.1359).
,
287.1360; C16H15D2N2O3
requires
þ
4.16. 4-Phenyl-3-benzoyl-oxazolidin-2-one (R)-22
1
2
In the same way as oxazolidinone 22, n-BuLi (0.56 ml,
2.5 M in hexane, 1.4 mmol), oxazolidinone (R)-6 (0.21 g,
1.28 mmol) and benzoyl chloride (0.22 g, 1.54 mmol) in
(142.40 and 139.90, 2C, ddt, JC,F = 251.3 Hz, JC,F =
3
12.2 Hz and JC,F = 3.8 Hz, C(2)–F), 139.4 (140.70 and
138.18, 1C, dtt, JC,F = 253.2 Hz, JC,F = 13.4 Hz and
1
2

3416
E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
3JC,F = 4.2 Hz, C(4)–F), 138.7 (i-C; Ph), 137.8 (139.05 and
ꢁ152.4 (2F, d, 3JF,F 17.1, Fortho), ꢁ157.9 (1F, t, 3JF,F 21.9,
1
2
3
136.58, 2C, dtdd, JC,F = 249.1 Hz, JC,F = 14.5 Hz,
Fpara) and ꢁ162.3 (2F, dd, JF,F 21.9 and 17.1, Fmeta
)
4
3JC,F = 5.7 Hz and JC,F = 3.1 Hz, C(3)–F), 128.9, 127.8
(found M, 330.0677; C16H11F5O2 requires 330.0674).
and 127.5 (3 · CH; Ar, · CH; Ph), 125.2 (1C, tdt,
4
3
2JC,F = 14.2 Hz, JC,F = 4.2 Hz and JC,F = 2.0 Hz, i-CO;
OC6F5), 45.1 (PhCH) and 18.5 (CH3CH); dF (378 MHz;
4.21. ( )-Pentafluorophenyl 2-tolylpropionate rac-29
3
CDCl3) ꢁ152.6 (2F, d, JF,F 20.9, Fortho), ꢁ157.9 (1F, t,
3
3JF,F 20.9, Fpara) and ꢁ162.3 (2F, t, JF,F 20.9, Fmeta
)
In the same way as the active ester rac-27, 2-tolylpropionic
acid rac-25 (2.19 g, 13.3 mmol), DCC (3.04 g, 14.7 mmol)
and pentafluorophenol (2.51 g, 13.6 mmol) in dichloro-
methane (20 ml), gave after purification by flash column
chromatography on silica gel eluting with light petroleum
ether/diethyl ether (9:1) gave, pentafluorophenyl 2-tolyl-
propionate rac-29 (2.85 g, 65%) as an oil; Rf [light petro-
leum (40–60 ꢁC)/diethyl ether (9:1)] 0.65; mmax (film)/cmꢁ1
1785 (C@O); dH (270 MHz; CDCl3) 7.24 (2H, d, J 8.2,
2 · CH; Ar), 7.18 (2H, d, J 8.2, 2 · CH; Ar), 4.03 (1H, q,
J 7.2, CH3CH), 2.34 (3H, s, CH3; Ar) and 1.62 (3H, d, J
7.2, CH3CH); dC (100 MHz; CDCl3) 170.6 (OC@O),
(found M+, 316.0514. C15H9F5O2 requires M+, 316.0517).
4.19. ( )-Pentafluorophenyl 2-phenylbutyrate rac-28
In the same way as the active ester rac-27, 2-phenylbutyric
acid rac-24 (5.0 g, 30.4 mmol), DCC (6.91 g, 33.4 mmol)
and pentafluorophenol (5.6 g, 30.4 mmol) in dichlorometh-
ane (40 ml), gave after purification by flash column chro-
matography on silica gel eluting with light petroleum
ether/diethyl ether (9:1) gave, pentafluorophenyl 2-phen-
ylbutyrate rac-28 (7.2 g, 72%) as a white needle-like solid;
Rf [light petroleum (40–60 ꢁC)/diethyl ether (1:1)] 0.70;
mp 41–43 ꢁC; mmax (CHCl3)/cmꢁ1 1700 (C@O); dH
(400 MHz; CDCl3) 7.41–7.27 (5H, m, 5 · CH; Ph), 3.83
(1H, t, J 7.7, CHO), 2.25 (1H, ddq, 13.7, 7.7 and 7.5,
CHAHBCH3), 1.95 (1H, ddq, 13.7, 7.7 and 7.5,
CHAHBCH3), 1.01 (3H, t, J 7.5, CH2CH3); dC (100 MHz;
CDCl3) 170.1 (OC@O), 141.2 (142.43 and 139.93, 2C,
1
141.1 (142.51 and 139.89, 2C, ddt, JC,F = 251.6 Hz,
2JC,F = 11.9 Hz and 3JC,F = 4.6 Hz, C(2)–F), 139.4
1
2
(140.63 and 138.12, 1C, dtt, JC,F = 252.8 Hz, JC,F
=
3
13.4 Hz and JC,F = 3.8 Hz, C(4)–F), 137.8 (139.07 and
1
2
136.56, 2C, dtdd, JC,F = 252.8 Hz, JC,F = 12.1 Hz,
3JC,F = 5.3 Hz and JC,F = 3.1 Hz, C(3)–F), 137.4 and
4
135.8 (2 · i-C; Ar), 129.5 and 127.2 (2 · CH; Ar), 125.2
1
2
3
2
4
3
ddtd, JC,F = 251.3 Hz, JC,F = 11.9 Hz, JC,F = 3.4 Hz
(1C, tdt, JC,F = 14.3 Hz, JC,F = 4.6 Hz and JC,F =
4
and JC,F = 3.4 Hz, C(2)–F), 139.5 (140.72 and 138.24,
1C, dtt, JC,F = 252.8 Hz, JC,F = 13.9 Hz and JC,F
2.3 Hz, i-CO; OC6F5), 44.6 (PhCH), 20.8 (CH3; Ar) and
18.4 (CH3CH) (found M+, 330.0671; C16H11F5O2 requires
330.0674).
1
2
3
=
3.8 Hz, C(4)–F), 137.9 (139.14 and 136.60, 2C, dtdd,
2
3
1JC,F = 254.3 Hz, JC,F = 14.2 Hz, JC,F = 4.9 Hz and
4JC,F = 2.6 Hz, C(3)–F), 137.3 (i-C; Ph), 128.3, 127.9 and
2
127.8 (3 · CH; Ph), 125.2 (1C, tdt, JC,F = 14.2 Hz,
4.22. ( )-Pentafluorophenyl 2-(4-isobutylphenyl)propionate
rac-30
4JC,F = 4.4 Hz and JC,F = 2.2 Hz, i-CO; OC6F5), 52.8
3
(PhCH), 26.7 (CH2) and 11.9 (CH3); dF (378 MHz; CDCl3)
3
ꢁ152.4 (2F, d, JF,F 17.1, Fortho), ꢁ157.9 (1F, t, 3JF,F 21.9,
In the same way as the active ester (rac)-27, 2-(4-isobutyl-
phenyl)propionic acid rac-26 (5 g, 24.3 mmol), DCC
(5.50 g, 26.7 mmol) and pentafluorophenol (4.65 g,
25.5 mmol) in dichloromethane (100 ml), gave after purifi-
cation by flash column chromatography on silica gel elut-
ing with light petroleum ether/diethyl ether (9:1),
pentafluorophenyl 2-(4-isobutylphenyl)propionate rac-30
(6.78 g, 75%) as a white needle-like solid; mp = 48–49 ꢁC;
Rf [light petroleum (40–60 ꢁC)/ether (9:1)] 0.63; mmax
(CHCl3)/cmꢁ1 1782 (CO); dH (270 MHz; CDCl3) 7.26
(2H, dt, J 8.2 and 2.2, 2 · CH; Ar), 7.14 (2H, dt, J 8.2
and 2.2, 2 · CH; Ar), 4.04 (1H, q, J 7.2, CHCO), 2.46
(2H, d, J 7.2, CH2CH), 1.92–1.80 (1H, m, CH(CH3)2),
1.62 (3H, d, J 7.2, CH3CHCO), 0.99 (3H, d, J 6.7,
3
Fpara) and ꢁ162.3 (2F, dd, JF,F 21.9 and 17.1, Fmeta
)
(found M, 330.0677; C16H11F5O2 requires 330.0674).
4.20. (+)-Pentafluorophenyl 2-phenylbutyrate (R)-28
In the same way as the active ester rac-27, (+)-2-phenylbu-
tyric acid (S)-24, DCC (6.91 g, 33.4 mmol) and pentafluoro-
phenol (5.6 g, 30.4 mmol) gave, pentafluorophenyl-2-
phenylbutyrate (R)-28 (7.58 g, 76%) as an oil; Rf [light
petroleum
(40–60 ꢁC)/diethyl
ether
(1:1)]
0.78;
20
20
½aꢂD ¼ þ69:5 (c 5.3, CHCl3) {for (S)-28; ½aꢂD ¼ ꢁ77:4 (c
34.8, CHCl3)}; mmax (CHCl3)/cmꢁ1 1700 (C@O); dH
(400 MHz; CDCl3) 7.41–7.27 (5H, m, 5 · CH; Ph), 3.83
(1H, t, J 7.7, CHO), 2.25 (1H, ddq, 13.7, 7.7 and 7.5,
CHAHBCH3), 1.95 (1H, ddq, 13.7, 7.7 and 7.5,
CHAHBCH3), 1.01 (3H, t, J 7.5, CH2CH3); dC (100 MHz;
CDCl3) 170.1 (OC@O), 141.2 (142.43 and 139.93, 2C,
(CH3)ACH(CH3)B) and 0.88 (3H, d,
J
6.7,
(CH3)BCH(CH3)A); dC (100 MHz; CDCl3) 170.3 (OC@O),
140.8 (i-C; Ar), 141.2 (142.92 and 139.42, 2C, ddt,
2
3
1JC,F = 251.3 Hz, JC,F = 11.9 Hz and JC,F = 4.2 Hz,
1
2
3
1
ddtd, JC,F = 251.3 Hz, JC,F = 11.9 Hz, JC,F = 3.4 Hz
C(2)–F), 138.9 (140.18 and 137.66, 1C, dtt, JC,F
253.2 Hz, JC,F = 13.8 Hz and JC,F = 3.8 Hz, C(4)–F),
=
4
2
3
and JC,F = 3.4 Hz, C(2)–F), 139.5 (140.72 and 138.24,
1
1C,
dtt,
1JC,F = 252.8 Hz,
2JC,F = 13.9 Hz
and
137.3 (138.61 and 136.08, 2C, dtdd, JC,F = 254.7 Hz,
3JC,F = 3.8 Hz, C(4)–F), 137.9 (139.14 and 136.60, 2C,
2JC,F = 14.5 Hz, JC,F = 5.3 and JC,F = 3.0 Hz, C(3)–F),
3
4
1
2
3
dtdd, JC,F = 254.3 Hz, JC,F = 14.2 Hz, JC,F = 4.9 Hz
135.5 (i-C; Ar), 129.1 and 126.7 (2 · CH; Ar), 124.7 (1C,
4
2
4
3
and JC,F = 2.6 Hz, C(3)–F), 137.3 (i-C; Ph), 128.3, 127.9
tdt, JC,F = 14.2 Hz, JC,F = 4.6 Hz and JC,F = 2.3 Hz,
i-CO; OC6F5), 44.5 (CH2; Ar), 44.4 (PhCH), 29.7
(CHCH2), 21.9 (CH(CH3)2) and 18.0 (CH3CH) (found
M, 372.1144; C19H17F5O2 requires 372.1143).
2
and 127.8 (3 · CH; Ph), 125.2 (1C, tdt, JC,F = 14.2 Hz,
4JC,F = 4.4 Hz and JC,F = 2.2 Hz, i-CO; OC6F5), 52.8
3
(PhCH), 26.7 (CH2) and 11.9 (CH3); dF (378 MHz; CDCl3)

E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
3417
4.23. (+)-Pentafluorophenyl-2-(6-methoxy-naphthalene-2-
yl)propionate (S)-35
PhCH), 4.63 (1H, t, J 9.0, CHAHBO), 4.08 (1H, dd, J 9.0
and 5.1, CHAHBO) and 1.39 (3H, d, J 6.9, CH3CH); dC
(62.9 MHz; CDCl3) 173.7 (NC@O), 153.2 (OC@O), 139.9
(i-C; PhA), 138.3 (i-C; PhB), 128.9, 128.7, 128.5, 128.2,
127.1 and 125.9 (6 · CH; PhA and PhB), 69.6 (CH2O),
57.9 (CHN), 43.9 (PhCH) and 18.6 (CH3) (found MH+,
In the same way as the active ester rac-27, (S)-(+)-6-meth-
oxy-(2-naphthyl)propionic acid (5.0 g, 21.7 mmol), DCC
(4.93 g, 23.9 mmol) and pentafluorophenol (4.0 g,
21.7 mmol) gave, pentafluorophenyl-2-(6-methoxy-naph-
thalene-2-yl)propionate (S)-35 (7.24 g, 84%) as a white
þ
296.1286; C15H18NO3 requires 296.1287).
powder; mp = 78–80 ꢁC; Rf [light petroleum (40–60 ꢁC)/
4.25. Synthesis of (4RR,2SS)-4-phenyl-3-[20-phenylbutyr-
yl]oxazolidin-2-one anti-32 and (4RR,2RR)-4-phenyl-3-[20-
phenylbutyryl]oxazolidin-2-one syn-32
20
ether (1:1)] 0.65; ½aꢂD ¼ þ93:6 (c 5.6, CHCl3); mmax
(CHCl3)/cmꢁ1 1781 (C@O); dH (250 MHz; CDCl3) 7.76–
7.13 (6H, m, 6 · CH; Ar), 4.38 (1H, q, J 7.2, CHCH3)
3.91 (3H, s, CH3) and 1.71 (3H, d, J 7.2, CH3CH); dC
(100 MHz; CDCl3) 170.7 (C@O), 157.9 (i-CO; Ar), 141.0
In the same way as oxazolidinone syn-31, n-BuLi (1.34 ml,
2.5 M in hexanes, 3.37 mmol), oxazolidinone (rac)-6 (0.4 g,
3.06 mmol) and pentafluorophenyl 2-phenylbutyrate (rac)-
28 (1.01 g, 3.06 mmol) in THF (5 ml), gave a separable pair
of diastereoisomers (ratio: syn-:anti->98:2). The residue
was purified by flash column chromatography on silica
gel eluting with light petroleum (bp 40–60 ꢁC)/diethyl ether
(7:3) to give the oxazolidinone anti-32 (ꢀ9 mg, 1%) as a vis-
cous oil; Rf [light petroleum (40–60 ꢁC)/diethyl ether (1:1)]
0.55; mmax (CHCl3)/cmꢁ1 1780 (C@O) and 1703 (C@O); dH
(250 MHz; CDCl3) 7.44–7.21 (10H, m, 10 · CH; 2 · Ph),
5.34 (1H, dd, J 8.7 and 3.4, CHN), 4.96 (1H, t, J 7.7,
PhCH), 4.54 (1H, br t, J 8.7, CHAHBO), 4.20 (1H, dd, J
8.7 and 3.4, CHAHBO), 2.01 (1H, ddq, J 13.6, 7.7 and
7.3, CHAHBCH3), 1.74 (1H, ddq, J 13.6, 7.7 and 7.3,
CHAHBCH3) and 0.76 (3H, t, J 7.4, CH3CH2); dC (62.9
MHz; CDCl3) 173.7 (NC@O), 153.4 (OC@O), 139.5 (i-C;
Ph), 138.6 (i-C; Ph), 129.1, 128.8, 128.7, 128.5, 127.3 and
125.8 (6 · CH; PhA and PhB), 69.4 (CH2O), 58.1 (CHN),
50.4 (PhCH), 27.7 (CH2Ph) and 12.0 (CH3) (found MH+,
310.1430; C19H20NO3 requires 310.1443) and oxazolidi-
none syn-32 (0.63 g, 69%) as a viscous oil; Rf [light petro-
leum (40–60 ꢁC)/diethyl ether (1:1)] 0.35; mmax (film)/cmꢁ1
1780 (C@O) and 1700 (C@O); dH (250 MHz; CDCl3)
7.26–6.87 (10H, m, 10 · CH; 2 · Ph), 5.46 (1H, dd, J 8.9
and 5.0, CHN), 4.90 (1H, t, J 7.5, CHCO), 4.63 (1H, t, J
8.9, CHAHBO), 4.07 (1H, dd, J 8.9 and 5.0, CHAHBO),
1.95 (1H, ddq, 13.6, 7.5 and 7.3, CHAHBCH3), 1.65 (1H,
ddq, 13.6, 7.5 and 7.3, CHAHBCH3) and 0.87 (3H, t, J
7.4, CH3CH2); dC (62.9 MHz; CDCl3) 173.2 (NC@O),
153.2 (OC@O), 138.4 (i-C; PhA), 138.1 (i-C; PhB), 128.9,2
128.8,2 128.4,1 128.3,2 127.21 and 125.72 (6 · CH; PhA
and PhB), 69.6 (CH2O), 57.8 (CHN), 51.2 (PhCH), 26.3
(CH2Ph) and 12.0 (CH3) (found MH+, 310.1437; C19H20-
NO3 requires 310.1443).
1
2
(142.32 and 139.82.67, 2C, ddt, JC,F = 249.8 Hz, JC,F
=
3
12.2 Hz and JC,F = 4.6 Hz, C(2)–F), 139.3 (140.63 and
1
2
138.11, 1C, dtt, JC,F = 252.1 Hz, JC,F = 13.0 Hz and
3JC,F = 4.5 Hz, C(4)–F), 137.8 (139.04 and 136.54, 2C,
1
2
3
dtdd, JC,F = 250.6 Hz, JC,F = 13.8 Hz, JC,F = 5.3 and
4JC,F = 3.0 Hz, C(3)–F), 133.9, 133.7 and 128.9 (3 · i-C;
Ar), 129.3, 127.5, 126.2, 125.7, 119.3 and 105.6 (6 · CH;
Ar), 125.2 (1C, m, i-CO; OC6F5), 55.3 (OCH3), 45.9
(ArCH) and 18.5 (CHCH3); dF (378 MHz; CDCl3)
3
3
ꢁ152.5 (2F, d, JF,F 17.0, Fortho), ꢁ157.9 (1F, t, JF,F
21.6, Fpara) and ꢁ162.3 (2F, dd, 3JF,F 21.6 and 17.0, Fmeta
)
(found M+, 396.0783; C20H13F5O requires 396.0779).
þ
3
4.24. Synthesis of (4RS,2RS)-3-(2-phenylpropionyl)-4-phen-
yl-oxazolidin-2-one anti-31 and (4RS,2RS)-3-(2-phenyl-
propionyl)-4-phenyl-oxazolidin-2-one syn-31
n-BuLi (4.86 ml, 3 M in hexane, 14.6 mmol) was added to a
stirred solution of oxazolidinone rac-6 (2 g, 12.2 mmol) in
THF at ꢁ78 ꢁC. After stirring for 1 h, a solution of penta-
fluorophenyl
2-phenylpropionate
(rac)-27
(4.99 g,
15.8 mmol) in THF (5.0 ml) was added. The resulting mix-
ture was stirred for 2 h at ꢁ78 ꢁC. The reaction was
quenched with water (10 ml). The organic layer was ex-
tracted with diethyl ether (2 · 10 ml), dried (over MgSO4)
and evaporated under reduced pressure to give a separable
mixture of two pairs of diastereoisomers (ratio: syn-:anti-
97:3) of oxazolidinones syn-31 and anti-31. The residue
was purified by flash column chromatography on silica
gel eluting with light petroleum (bp 40–60 ꢁC)/diethyl ether
(1:1) to give oxazolidinone anti-31 (71 mg, ꢀ2%) as white
needle-like crystals; Rf [light petroleum (40–60 ꢁC)/diethyl
ether (1:1)] 0.40; mp 106–108 ꢁC; mmax (CHCl3); cmꢁ1
1780 (C@O) and 1700 (C@O); dH (270 MHz; CDCl3)
7.39–7.26 (10H, m, 10 · CH; 2 · Ph), 5.32 (1H, dd, J 8.8
and 3.2, CHN), 5.11 (1H, q, J 7.2, PhCH), 4.55 (1H, t, J
8.8, CHAHBO), 4.21 (1H, dd, J 8.8 and 3.2, CHAHBO)
and 1.40 (3H, d, J 7.2, CH3CH); dC (62.9 MHz; CDCl3)
174.1 (NC@O), 152.9 (OC@O), 140.2 (i-C; PhA), 139.4 (i-
C; PhB), 129.3, 128.7, 128.6, 128.2, 127.3 and 125.8
(6 · CH; PhA and PhB), 69.7 (CH2O), 58.1 (CHN), 43.2
(PhCH) and 19.4 (CH3) (found MH+, 296.1282;
4.26. Synthesis of (4RR,2RR)-3-[20-(4-methylphenyl)propi-
onyl]-4-phenyl-oxazolidin-2-one anti-33 and (4RR,2SS)-3-
[20-(4-methylphenyl)propionyl]-4-phenyl-oxazolidin-2-one
syn-33
In the same way as oxazolidinone syn-31, n-BuLi (0.71 ml,
2 M in hexane, 1.42 mmol), oxazolidinone rac-6 (0.2 g,
1.22 mmol) and pentafluorophenyl 2-(4-methylphenyl)pro-
pionate rac-29 (0.46 g, 1.39 mmol) in THF (5 ml), gave a
separable pair of diastereoisomers (ratio: syn-33:anti-
33 => 95:5). The residue was purified by flash column
chromatography on silica gel eluting with light petroleum
(bp 40–60 ꢁC)/diethyl ether (7:3) to give oxazolidinone
anti-33 (8 mg, ꢀ2%) as an oil; Rf [light petroleum
þ
C18H18NO3 requires 296.1287); and oxazolidinone syn-
31 (2.51 g, 70%) as a white solid; Rf [light petroleum (40–
60 ꢁC)/diethyl ether (1:1)] 0.30; mp 124–125 ꢁC; mmax
(CHCl3)/cmꢁ1 1780 (C@O) and 1705 (C@O); dH
(270 MHz; CDCl3) 7.29–7.21 (10H, m, 10 · CH; 2 · Ph),
5.45 (1H, dd, J 9.0 and 5.1, CHN), 5.09 (1H, q, J 6.9,

3418
E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
(40–60 ꢁC)/diethyl ether (1:1)] 0.50; mmax (CHCl3)/cmꢁ1
1779 (C@O) and 1703 (C@O); dH (270 MHz; CDCl3)
7.35–7.23 (5H, m, 5 · CH; Ph), 7.18 (2H, dt, J 8.0 and
2.0, 2 · CH; Ar), 7.05 (2H, br d, J 8.0, 2· CH; Ar), 5.33
(1H, dd, J 8.9 and 2.9, CHN), 5.08 (1H, q, J 7.1, ArCH),
4.54 (1H, t, J 8.9, CHAHBO), 4.20 (1H, dd J 8.9 and 3.2,
CHAHBO), 2.33 (3H, s, CH3; Ar) and 1.39 (3H, d, J 7.1,
CH3CHAr); dC (100.6 MHz; CDCl3) 174.2 (NC@O),
153.2 (OC@O), 140.6 (i-C; Ar), 139.4 (i-C; Ar), 137.2 (i-
C; Ar), 136.9 (i-C; Ph), 129.3 and 128.0 (2 · CH; Ar),
128.8, 128.5 and 125.8 (3 · CH; Ph), 69.7 (CH2O), 58.1
(CHN), 42.8 (ArCH), 21.0 (CH3; Ar) and 19.4 (CH3CH)
(C@O) and 1705 (C@O); dH (270 MHz; CDCl3) 7.28–7.15
(3H, m, 3 · CH; Ph and/or Ar), 7.00 (4H, m, 4 · CH, Ph
and Ar), 6.90 (2H, dt, J 7.9 and 1.9, 2 · CH; Ar), 5.44
(1H, dd J 9.2 and 5.2, CHN), 5.09 (1H, q, J 6.9, ArCH),
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, CH2), 1.89–1.79 (1H, m,
CH(CH3)2), 1.38 (3H, d, J 6.9, CH3CH) and 0.90 (6H, d,
J 6.7, 2 · CH3, CHA3 CHCH3B); dC (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), 129.3 and 127.0 (2 · CH; Ar),
129.2, 128.7 and 125.8 (3 · CH; Ph), 69.7 (CH2O), 58.1
(CHN), 45.1 (CH(CH3)2), 42.7 (ArCH), 30.2 (CH2), 22.4
(2C, s, CHACHCHB) and 19.4 (CH3CH2) (found MH+,
þ
þ
(found MNH4
,
327.1700; C19H23N2O3
requires
3
3
327.1709); and oxazolidinone syn-33 (0.24 g, 62%) as a
white solid; Rf [light petroleum (40–60 ꢁC)/diethyl ether
(1:1)] 0.30; mp 102–104 ꢁC [(S,R)-33; mp 107–109 ꢁC]; mmax
(CHCl3)/cmꢁ1 1780 (C@O) and 1700 (C@O); dH
(270 MHz; CDCl3) 7.28–7.15 (3H, m, 3 · CH; Ph and/or
Ar), 7.10–6.90 (6H, m, 6 · CH, Ph and Ar), 5.44 (1H, dd,
J 8.9 and 5.0, CHN), 5.05 (1H, q, J 6.9; ArCH), 4.63
(1H, t, J 8.9, CHAHBO), 4.07 (1H, dd, J 8.9 and 5.2,
CHAHBO), 2.32 (3H, s, CH3; Ar) and 1.34 (3H, d, J 6.9,
CH3CH); dC (100.6 MHz; CDCl3) 173.8 (NC@O), 153.1
(OC@O), 138.7 (i-C; Ar), 136.9 (i-C; Ar), 136.5 (i-C; Ph),
129.3 and 127.3 (2 · CH; Ar), 129.2, 128.7 and 125.9
352.1909; C22H26NO3 requires 352.1907).
4.28. Parallel kinetic resolution of pentafluorophenyl 2-
phenylpropionate rac-27 using a quasi-enantiomeric combi-
nation of oxazolidinones (R)-6 and (S)-[D2]-6
n-BuLi (0.50 ml, 2.5 M in hexanes, 1.23 mmol) was added
to a stirred solution of oxazolidinone (R)-6 (99 mg,
0.60 mmol) and (S)-[D2]-6 (0.10 g, 0.60 mmol) in THF
at ꢁ78 ꢁC. After stirring for 1 h, a solution of penta-
fluorophenyl 2-phenyl-propionate (rac)-27 (0.46 mg,
1.45 mmol) in THF (5.0 ml) was added. The resulting mix-
ture was stirred for 2 h at ꢁ78 ꢁC. The reaction was
quenched with water (10 ml). The organic layer was ex-
tracted with diethyl ether (2 · 10 ml), dried (over MgSO4)
and evaporated under reduced pressure to give a separable
mixture of two pairs of diastereoisomers (ratio: syn-:anti-
> 97:3) of oxazolidinones syn-31 and syn-[D2]-31, and
anti-31 and anti-[D2]-31. The residue was purified by flash
column chromatography on silica gel eluting with light
petroleum (bp 40–60 ꢁC)/diethyl ether (1:1) to give oxazo-
lidinones anti-31 and anti-[D2]-31 (11 mg, ꢀ3%) [ratio
(3 · CH; Ph), 69.6 (CH2O), 57.9 (CHN), 43.4 (ArCH),
þ
22.6 (CH3; Ar) andþ 19.4 (CH3CH) (found MNH4
,
327.1701; C19H23N2O3 requires 327.1709).
4.27. Synthesis of (4RR,2RR)-3-[20-(4-isobutylphenyl)propi-
onyl]-4-phenyl-oxazolidin-2-one anti-34 and (4RR,2SS)-3-
[20-(4-isobutylphenyl)propionyl]-4-phenyl-oxazolidin-2-one
syn-34
In the same way as oxazolidinone syn-31, n-BuLi (0.73 ml,
2 M in hexane, 1.46 mmol), oxazolidinone (rac)-6 (0.21 g,
1.2 mmol) and pentafluorophenyl 2-(4-isobutylphenyl)pro-
pionate (rac)-30 (0.53 g, 1.42 mmol) in THF (5 ml), gave
a separable pair of diastereoisomers (ratio: syn-34:anti-
34 = 96:4). The residue was purified by flash column chro-
matography on silica gel eluting with light petroleum (bp
40–60 ꢁC)/diethyl ether (7:3) to give oxazolidinone anti-34
(47 mg, ꢀ1%) as an oil; Rf [light petroleum (40–60 ꢁC)/
diethyl ether (1:1)] 0.62; mp 150–154 ꢁC; [for (R,R)-anti-
34; mp = 155–158 ꢁC]; mmax (CHCl3)/cmꢁ1 1780 (C@O)
and 1701 (C@O); dH (270 MHz; CDCl3) 7.39–7.23 (7H,
m, 7 · CH; Ar and Ph), 7.07 (2H, dt, J 8.2 and 1.9,
2 · CH, Ar), 5.33 (1H, dd, J 8.4 and 3.2, CHN), 5.10
(1H, q, J 7.1, ArCH), 4.55 (1H, t, J 8.9, CHAHBO), 4.20
(1H, dd J 8.9 and 3.2, CHAHBO), 2.42 (2H, d, J 7.2,
CH2), 1.88–1.78 (1H, m, CH (CH3)2), 1.39 (3H, d, J 7.1,
50:50 ( 2%)] as a white solid; Rf [light petroleum/
20
diethyl ether (1:1)] 0.62; mp = 94–96 ꢁC; ½aꢂD ¼ ꢁ0:5 (c
0.1, CHCl3); mmax (CHCl3)/cmꢁ1 2364 (CD), 1780 (C@O)
and 1700 (C@O); dH (400 MHz; CDCl3) 7.35–7.15 (20H,
m, 20 · CH, ArU, ArL, PhU and PhL), 5.27 (1H, dd, J 9.1
and 3.3, CHNCHU2 ), 5.26 (1H, s, CHNCDL2 ), 5.08 (2H,
q, J 6.9, ArCHCHU3 and ArCHCHL3 ), 4.89 (1H, t, J 8.9,
CHAHBOU), 3.97 (1H, dd, J 8.9 and 3.3, CHAHBOU)
and 1.34 (6H, d, J 6.9, ArCHCHU3 and ArCHCH3L); dC
(100 MHz; CDCl3) 174.0 (NC@OU and NC@OL), 153.47
(OC@OU and OC@OL), 140.1 (i-C; PhU and PhL),
139.3 (2 · i-C; PhU and PhL), 129.2,4 128.7,2 128.5,4
128.1,4 127.22 and 125.7,4 (20 · CH; ArU, ArL, PhU and
PhL), 69.7 (CH2OU), 58.0 (CHNU), 57.9 (CHNL), 43.2
(PhCHU and PhCHL), 19.3 (CHCH3U and CHCHL3 ) (found
MUNH4þ, 313.1548; C18H21NO3 requires 313.1547) and
(found MUNH4
,
315.1670; C18H29D2NO3 requires
þ
CH3CHAr) and 0.89 (6H, d,
J
6.7, 2 · CH3,
CHA3 CHCH3B); dC (100.6 MHz; CDCl3) 173.9 (NC@O),
153.2 (OC@O), 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, 128.5 and
125.8 (3 · CH; Ph), 69.6 (CH2O), 57.8 (CHN), 45.1
(CH(CH3)2), 43.3 (ArCH), 30.2 (CH2), 22.4 (2C, s,
CHA3 CHCHB3 ) and 18.5 (CH3CH2) (found MH+,
352.1913; C22H26NO3 requires 352.1907); and oxazolidi-
none syn-34 (0.24 g, 56%) as a white solid; Rf [light petro-
leum (40–60 ꢁC)/diethyl ether (1:1)] 0.43; mp 69–71 ꢁC [for
(S,R)-syn-34; mp = 97–99 ꢁC]; mmax (CHCl3)/cmꢁ1 1779
325.1670). By mass spectrometry, found anti-31: anti-
[D2]-31 ratio: 52:48. Proton NMR shift: negative isotopic
shift at 5.27 ppm (CHN) was 0.0098 ppm (3.94 Hz at
400 MHz). Carbon NMR shifts: (a) negative isotopic shift
at 57.9 ppm (CHN) was 0.1757 ppm (17.6 Hz at
100.6 MHz); and syn-31:syn-[D2]-31 [ratio 52:48 ( 2%)]
(0.24 g, 70%); Rf [light petroleum/diethyl ether (1:1)] 0.43;
20
mp = 106–108 ꢁC; ½aꢂD ¼ þ1:8 (c 4.6, CHCl3); mmax
(CHCl3)/cmꢁ1 2360 (CD), 1780 (C@O) and 1700 (C@O);
dH (400 MHz; CDCl3) 7.25–7.09 (12H, m, 6 · CH,

E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
3419
PhU and PhL), 7.03–7.00 (4H, m, 2 · CH, ArU, ArL, PhU
and PhL), 6.86–6.83 (4H, m, 2 · CH, ArU and ArL), 5.36
(1H, dd, J 9.1 and 5.1, CHNCHU2 ), 5.36 (1H, s, CHNCD2L),
5.02 (2H, q, J 7.0, ArCHCHU3 and ArCHCH3L), 4.54
(1H, t, J 9.1, CHAHBOU), 3.97 (1H, dd, J 9.1 and 5.1, CHA
C19H21D2N2O3 requires 329.1834; isotopic shifts by
NMR spectroscopy. By mass spectrometry, found anti-
32: anti-[D2]-32 ratio: 51:49. Proton NMR shift: negative
isotopic shift at 5.34 ppm (CHN) was 0.0103 ppm
(4.10 Hz at 400 MHz). Carbon NMR shifts: (a) negative
isotopic shift at 69.6 ppm (CH2O) was 0.410 ppm (41 Hz
at 100.6 MHz); (b) negative isotopic shift at 58.2 ppm
(CHN) was 0.168 ppm (16.91 Hz at 100.6 MHz); and the
oxazolidinones syn-32 and syn-[D2]-32 (0.34 g, 87%) [ratio
þ
HBOU) and 1.30 (6H, d,
J
7.0, ArCHCHU3 and
ArCHCHL); dC (100 MHz; CDCl3) 173.5 (NC@OU and
3
NC@OL), 153.0 (OC@OU) and 152.9 (OC@OL), 139.7
(i-C; PhU and PhL), 139.1 (2 · i-C; PhU and PhL), 128.7,4
128.4,6 128.04 127.02 and 125.74 (20 · CH; ArU, ArL, PhU
and PhL), 69.4 (CH2OU), 68.8 (1C, quintet, J 22.6, CD2OL),
57.6 (CHNU), 57.5 (CHNL), 43.7 (PhCHU and PhCHLþ),
50:50 ( 2%)] as a white solid; Rf [light petroleum (40–
20
60 ꢁC)/diethyl ether (1:1)] 0.35; mp 69–72 ꢁC; ½aꢂD ¼ þ1:1
(c 6, CHCl3); mmax (CHCl3)/cmꢁ1 2310 (CD), 1780 (C@O)
and 1700 (C@O); dH (400 MHz; CDCl3) 7.28–7.15 (12H,
m, 6 · CH, PhU and PhL), 7.10–7.08 (4H, m, 2 · CH,
PhU and PhL), 6.90–6.85 (4H, m, 2 · CH, PhU and PhL),
5.48 (1H, dd, J 9.1 and 5.0, CHNCHU2 ), 5.46 (1H,
s, CHNCDL2 ), 4.91 (2H, t, J 7.5, PhCHCHU2 and
18.5 (CHCHU3 and CHCH3L) (found MUNH4
,
313.1543; C18H21NO3 requires 313.1547 and found
MLNH4þ, 315.1673; C18H29D2NO3 requires 325.1672).
By mass spectrometry, found syn-31: syn-[D2]-31 ratio:
54:46. (By EI, found MU+, 295.1199; C18H17NO3 requires
295.15203 and found ML+, 297.1325; C18H15D2NO3 re-
quires 297.1332). Proton NMR shift: negative isotopic shift
at 5.35 ppm (CHN) was 0.0098 ppm (3.92 Hz at 400 MHz).
Carbon NMR shifts: (a) negative isotopic shift at
153.0 ppm (i-C; Ph) was 0.011 ppm (1.15 Hz at
100.6 MHz); (b) negative isotopic shift at 69.4 ppm
(CH2O) was 0.645 ppm (64.9 Hz at 100.6 MHz); (c) nega-
tive isotopic shift at 57.5 ppm (CHN) was 0.1726 ppm
(17.4 Hz at 100.6 MHz).
PhCHCHL), 4.63 (1H, t, J 9.0, CHAHBOU), 3.97 (1H,
2
dd, J 9.0 and 5.0, CHAHBOU) and 1.95 (2H, ddq, 13.6,
7.5 and 7.3, CHAHBCHU and CHAHBCHL), 1.65 (2H,
3
3
ddq, 13.6, 7.5 and 7.3, CHAHBCHU and CHAHBCHL)
3
and 0.87 (6H, t, J 7.3, CH3CHU 3 and CH3CHL); dC
2
2
(100 MHz; CDCl3) 172.8 (NC@OU and NC@OL), 153.0
(OC@OU and OC@OL), 138.2 (i-C; PhU), 138.1 (i-C;
PhL), 137.9 (2 · i-C; ArU and ArL), 128.6,4 128.5,4 128.2,4
128.1,2 126.92 and 125.54 (20 · CH; ArU, ArL, PhU and
1
PhL), 69.3 (CH2OU), 68.7 (1C, quintet, JCD = 23.8 Hz,
4.29. Parallel kinetic resolution of pentafluorophenyl
2-phenylbutyrate rac-28 using a quasi-enantiomeric combi-
nation of oxazolidinones (R)-6 and (S)-[D2]-6
CD2OL), 57.4 (CHNU), 57.3 (CHNL), 51.0 (ArCHU and
ArCHL), 26.0 (CH3CHU and CH3CHL) and 18.3
2
2
(CH3CHU and CH3þCHL); For syn-32; found MH+,
2
2
310.1436; C19H20NO3 requires 310.1438; and syn-[D2]-32
In the same way as oxazolidinone syn-31, n-BuLi (0.43 ml,
3 M in hexane, 1.3 mmol), oxazolidinone (R)-6 (0.103 g,
0.63 mmol), oxazolidinone (S)-[D2]-6 (0.104 g, 0.63 mmol)
and pentafluorophenyl 2-phenylbutyrate (rac)-28 (0.45 g,
1.38 mmol) in THF (10 ml), gave a separable mixture of
two pairs of diastereoisomers (ratio: syn-32 and syn-[D2]-
32: anti-32 and anti-[D2]-32 => 98:2). The residue was puri-
fied by flash column chromatography on silica gel eluting
with light petroleum (bp 40–60 ꢁC)/diethyl ether (7:3) to
give oxazolidinone anti-32 and anti-[D2]-32 (<5 mg, 1%)
[ratio 50:50 ( 2%)] as a white solid; Rf [light petroleum
found MH+, 312.1563; C19H18D2NO requires 312.1563.
þ
3
By mass spectrometry, found syn-32: syn-[D2]-32 ratio:
52:48.
Isotopic shifts by NMR spectroscopy. Proton NMR shift:
negative isotopic shift at 5.46 ppm (CHN) was
0.00985 ppm (3.94 Hz at 400 MHz). Carbon NMR shifts:
(a) negative isotopic shift at 138.1 ppm (i-C; Ph) was
0.0306 ppm (3.07 Hz at 100.6 MHz); (b) negative isotopic
shift at 69.3 ppm (CH2O) was 0.649 ppm (65.3 Hz at
100.6 MHz); (c) negative isotopic shift at 57.4 ppm
(CHN) was 0.091 ppm (9.22 Hz at 100.6 MHz).
(40–60 ꢁC)/diethyl ether (1:1)] 0.55; mp = 110–112 ꢁC;
20
½aꢂD ¼ꢀ 0:0 (c 0.9, CHCl3); mmax (CHCl3)/cmꢁ1 2306
(CD), 1781 (C@O) and 1701 (C@O); dH (400 MHz; CDCl3)
7.45–7.15 (20H, m, 10 · CH, PhU and PhL), 5.36 (1H, dd, J
8.8 and 3.4, CHNCHU2 ), 5.34 (1H, s, CHNCDL2 ), 4.95 (2H,
t, J 7.7, PhCHCHU2 and PhCHCHL2 ), 4.57 (1H, t, J 8.8,
CHAHBOU), 4.21 (1H, dd, J 8.8 and 3.4, CHAHBOU),
4.30. Parallel kinetic resolution of pentafluorophenyl 2-(4-
methylphenyl)propionate rac-29 using a quasi-enantiomeric
combination of oxazolidinones (R)-6 and (S)-[D2]-6
In the same way as oxazolidinone syn-31, n-BuLi (0.43 ml,
3 M in hexane, 1.3 mmol), oxazolidinone (R)-6 (0.104 g,
0.63 mmol), oxazolidinone (S)-[D2]-6 (0.104 g, 0.63 mmol)
and pentafluorophenyl 2-(4-methylphenyl)propionate
(rac)-29 (0.51 g, 1.54 mmol) in THF (10 ml), gave after
purification by flash column chromatography on silica gel
eluting with light petroleum ether/ether (7:3) a separable
mixture of two pairs of diastereoisomers (ratio: syn-33
and syn-[D2]-33: anti-33 and anti-[D2]-33 = 96:4). The resi-
due was purified by flash column chromatography on silica
gel eluting with light petroleum (bp 40–60 ꢁC)/diethyl ether
(7:3) to give oxazolidinone anti-33 and anti-[D2]-33 [ratio
1.94 (2H, ddq, 13.6, 7.7 and 7.3, CHAHBCHU and
3
CHAHBCHL), 1.64 (2H, 13.6, 7.7 and 7.3, CHAHBCHU
3
and CHAH3BCHL) and 0.78 (6H, t, J 7.5, CH3CHU and
3
2
CH3CHL); dC (100 MHz; CDCl3) 173.8 (NC@OU and
2
NC@OL), 153.4 (OC@OU and OC@OL), 139.4 (i-C;
PhU and PhL), 138.6 (2 · i-C; ArU and ArL), 129.3,4
128.9,4 128.8,2 128.6,4 127.42 and 125.94 (20 · CH; ArU,
ArL, PhU and PhL), 69.6 (CH2OU), 69.2 (1C, quintet,
1JCD = 22.9 Hz, CD2OL), 58.2 (CHNU), 57.9 (CHNL),
50.4 (ArCHU and ArCHL), 27.7 (CH3CHU and
2
CH3CHL) and 14.0 (CH3CHU and CH3CHL); For anti-
2
2
2
32; found MNH4þ, 327.1700; C19H23N2O
requires
327.1709, and anti-[D2]-32; found MNH4þ3, 329.1831;
51:49 ( 2%)] (8 mg, ꢀ2%) as a white solid; Rf [light petro-
þ
20
leum/diethyl ether (1:1)] 0.50; mp = 80–82 ꢁC; ½aꢂD
¼

3420
E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
ꢁ0:5 (c 0.2, CHCl3); mmax (CHCl3)/cmꢁ1 2315 (CD), 1780
(C@O) and 1700 (C@O); dH (400 MHz; CDCl3) 7.35–7.23
(10H, m, 5 · CH, PhU and PhL), 7.17 (4H, d, J 7.8, 4 · CH;
ArU and ArL), 7.06 (4H, d, J 7.8, 4 · CH; ArU and ArL),
5.25 (1H, dd, J 8.9 and 3.2, CHNCHU2 ), 5.24 (1H, s,
(rac)-20 (0.57 mg, 1.52 mmol) in THF (5 ml), gave after
purification by flash column chromatography on silica gel
eluting with light petroleum ether/ether (7:3) a separable
mixture of two pairs of diastereoisomers (ratio: syn-34
and syn-[D2]-34: anti-34 and anti-[D2]-34 = 97:3). The resi-
due was purified by flash column chromatography on silica
gel eluting with light petroleum (bp 40–60 ꢁC)/diethyl ether
(7:3) to give oxazolidinone anti-34 and anti-[D2]-34 ([ratio
52:48 ( 2%)]) (8 mg, ꢀ2%) as a white solid; Rf [light
CHNCDL2 ), 5.02 (2H, q,
J
6.9, ArCHCHU3 and
ArCHCHL), 4.48 (1H, t, J 8.9, CHAHBOU), 4.15 (1H,
3
dd, J 8.9 and 3.2, CHAHBOU) and 2.25 (6H, s, ArCHU
3
and ArCHL3 ) and 1.32 (6H, d, J 6.9, ArCHCHU3 and
ArCHCHL3 ); dC (100 MHz; CDCl3) 174.2 (NC@OU and NC@
OL), 153.3 (OC@OU and OC@OL), 138.3 (2 · i-C;
PhU and PhL), 137.1 (2 · i-C; ArU and ArL), 136.9 (2 · i-
C; ArU and ArL), 129.3,4 129.2,4 128.7,2 128.04 and
125.84 (18 · CH; ArU, ArL, PhU and PhL), 69.8 (CH2OU),
58.0 (CHNU), 57.9 (CHNL), 42.7 (ArCHU and ArCHL),
petroleum/diethyl ether (1:1)] 0.62; mp = 103–105 ꢁC;
20
½aꢂD ¼ ꢁ0:8 (c 0.3, CHCl3); mmax (CHCl3)/cmꢁ1 2365
(CD), 1778 (C@O) and 1701 (C@O); dH (400 MHz; CDCl3)
7.34–7.16 (14H, m, 7 · CH, ArU, ArL, PhU and PhL), 7.01
(4H, dt, J 8.2 and 1.8, 2 · CH, ArU and ArL), 5.26 (1H, dd,
J 8.7 and 3.3, CHNCH2U), 5.25 (1H, s, CHNCDL2 ), 5.04
19.3 (ArCHU3 and ArCHL) and 14.1 (CH3CHU and
(2H, q, J 6.9, ArCHCHU3 and ArYCHCHL), 4.49 (1H, t,
3
3
CH3CHL); (found MUNH þ, 327.1703; C19H23N2O3 re-
J 8.7, CHAHBOU), 4.14 (1H, dd, J 8.7 and 3.3, CHAHBOU)
4
quires 327.1700 and found MLNH4
,
329.1830;
and 2.36 (4H, dd, J 8.3 and 1.8, ArCHU2 and ArCH2L), 1.79–
þ
U
L
C19H23N2O3 requires 327.1829). By mass spectrometry,
found anti-33: anti-[D2]-33 ratio: 53:47. Proton NMR shift:
negative isotopic shift at 5.25 ppm (CHN) was 0.0101 ppm
(4.08 Hz at 400 MHz). Carbon NMR shifts: (a) negative
isotopic shift at 57.9 ppm (CHN) was 0.168 ppm (16.9 Hz
at 100.6 MHz); and syn-33:syn-[D2]-33 [ratio 50:50 ( 2%)]
1.72 (2H, m, CHðCH3Þ2 and CHðCH3Þ2 ), 1.41 (6H, d, J
6.9, ArCHCHU3 and ArCHCH3LL) and 0.85–0.75 (12H, d, J
U
6.9, CHðCH3Þ2 and CHðCH3Þ2 ); dC (100 MHz; CDCl3)
174.4 (NC@OU and NC@OL), 153.3 (OC@OU and
OC@OL), 140.8 (2 · i-C; ArU and ArL), 139.5 (i-C; PhU),
139.4 (i-C; PhL), 137.4 (2 · i-C; ArU and ArL), 129.4,4
129.3,4 128.7,2 127.94 and 125.94 (18 · CH; ArU, ArL,
PhU and PhL), 69.7 (CH2OU), 58.1 (CHNU), 58.0 (CHNL),
(0.27 g, 69%); Rf [light petroleum/diethyl ether (1:1)] 0.30;
20
mp = 74–76 ꢁC; ½aꢂD ¼þ1:3 (c 9.0, CHCl3); mmax
U
L
(CHCl3)/cmꢁ1 2355 (CD), 1780 (C@O) and 1700 (C@O);
dH (400 MHz; CDCl3) 7.30–7.20 (6H, m, 6 · CH, PhU
and PhL), 7.10–6.95 (12H, m, 12 · CH, PhU, PhL, ArU
and ArL), 5.46 (1H, dd, J 9.0 and 5.2, CHNCHU2 ), 5.45
(1H, s, CHNCDL2 ), 5.09 (2H, q, J 6.9, ArCHCHU3 and
45.2 (CHðCH3Þ and CHðCH3Þ ), 42.8 (ArCHU and
2
ArCHL), 30.2 (CH2U and CH2L), 222.4 (CHACH3BCHL3 and
CHACHBCHL) and 19.5 (CH3CHU and CH3CHL); (found
3
3
MUNH4þ, 369.2þ171; C22H29N2O3 requires 369.2173 and
found MLNH4
,
371.2296; C22H27D2N2O3 requires
ArCHCHL), 4.61 (1, t, J 8.9, CHAHBOU), 4.05 (1H, dd,
371.2298). By mass spectrometry, found anti-31: anti-
[D2]-31 ratio: 54:46. Proton NMR shift: negative isotopic
shift at 5.27 ppm (CHN) was 0.00965 ppm (3.86 Hz at
400 MHz). Carbon NMR shifts: (a) negative isotopic shift
at 139.4 ppm (i-C; Ph) was 0.0344 ppm (3.44 Hz at
100.6 MHz); (b) negative isotopic shift at 58.1 ppm
(CHN) was 0.172 ppm (17.3 Hz at 100.6 MHz); and syn-
34:syn-[D2]-34 [ratio 50:50 ( 2%)] (0.35 g, 79%) as a white
3
J 8.9 and 5.2, CHAHBOU) and 2.34 (6H, s, ArCHU and
ArCHL3 ) and 1.30 (6H, d,
J
6.9, ArCHCHU3 3 and
ArCHCHL3 ); dC (100 MHz; CDCl3) 173.6 (NC@OU and
NC@OL), 152.9 (OC@OU and OC@OL), 138.2 (i-C;
PhU), 138.1 (i-C; PhL), 136.7 (2 · i-C; ArU and PhL),
136.6 (2 · i-C; ArU and ArL), 129.9,4 128.6,4 128.2,2
127.84 and 125.74 (18 · CH; ArU, ArL, PhU and PhL),
69.3 (CH2OU), 68.7 (1C, quintet, 1JCD = 24.5 Hz, CD2OL),
57.5 (CHNU), 57.4 (CHNL), 43.0 (ArCHU and ArCHL),
20.9 (ArCHU3 and ArCH3L) and 18.5 (CH3CHU
and CH3CHL); (found MU+, 309.1360; C19H19NO3 re-
quires 309.1359 and found ML+, 311.1485; C19H17D2NO3
requires 311.1485). By mass spectrometry, found syn-33:
syn-[D2]-33 ratio: 51:49. Proton NMR shift: negative isoto-
pic shift at 5.45 ppm (CHN) was 0.0098 ppm (3.92 Hz at
400 MHz). Carbon NMR shifts: (a) negative isotopic shift
at 138.1 ppm (i-C; Ph) was 0.0306 ppm (3.07 Hz at
100.6 MHz); (b) negative isotopic shift at 69.3 ppm
(CH2O) was 0.641 ppm (64.5 Hz at 100.6 MHz); (c) nega-
tive isotopic shift at 57.5 ppm (CHN) was 0.168 ppm
(16.9 Hz at 100.6 MHz).
solid; Rf [light petroleum/diethyl ether (1:1)] 0.43; mp =
20
71–73 ꢁC; ½aꢂD ¼ þ1:1 (c 2.0, CHCl3); mmax(CHCl3)/
cmꢁ1 2361 (CD), 1781 (C@O) and 1703 (C@O); dH
(400 MHz; CDCl3) 7.28–7.16 (6H, m, 3 · CH, PhU and
PhL), 6.97–6.88 (8H, m, 4 · CH, ArU, ArL, PhU and
PhL), 6.82 (4H, dt, J 7.1 and 1.5, 2 · CH, ArL and ArU),
5.36 (1H, dd, J 8.9 and 5.1, CHNCH2), 5.35 (1H, s,
CHNCD2), 5.02 (2H, q, J 7.0, ArLCHCH3 and Ar-
UCHCH3), 4.52 (1H, t, J 8.9, CHAHBO), 3.96 (1H, dd, J
8.9 and 5.1, CHAHBO) and 2.36 (4H, dd, J 7.1 and 2.2,
U
ArUCH2 and ArLCH2), 1.89–1.82 (2H, m, CHðCH3Þ
and CHðCH3Þ ), 1.30 (6H, d, J 7.0, ArCHCHU an2d
L
2
3
ArCHCHL3 ) and 0.95 (6H, J 6.7, CHACH3BCHU3 and
CHACHB3 CHL3 ) and 0.93 (6H, J 6.7, CHACH3BCHU3
and CHACH3BCHL3 ); dC (100 MHz; CDCl3) 173.7 (NC@OU
and NC@OL), 153.0 (OC@OU and OC@OL), 140.3 (2 · i-
C; ArU and ArL), 138.2 (i-C; PhU), 138.1 (i-C; PhL),
136.8 (2 · i-C; ArU and ArL), 129.0,4 128.6,4 128.3,2
127.74 and 125.64 (18 · CH; ArU, ArL, PhU and PhL),
4.31. Parallel kinetic resolution of pentafluorophenyl 2-(4-
isobutylphenyl)propionate rac-20 using a quasi-enantiomeric
combination of oxazolidinones (R)-6 and (S)-[D2]-6
In the same way as oxazolidinone syn-31, n-BuLi (0.43 ml,
3 M in hexane, 1.3 mmol), oxazolidinone (R)-6 (0.102 g,
0.62 mmol), oxazolidinone (S)-[D2]-6 (0.103 g, 0.62 mmol)
and pentafluorophenyl 2-(4-isobutylphenyl)propionate
69.3 (CH2OU), 68.7 (1C, quintet, 1JCD = 22.9 Hz, CD2OL),
U
57.5 (CHNU), 57.3 (CHNL), 44.8 (CHðCH3Þ and
2
L
CHðCH3Þ ), 43.1 (ArCHU and ArCHL), 30.0 (CHU2
2
and CHL2 ), 22.3 (2 ꢃ CHACH3BCHL3 ), 22.1 (2ꢃ

E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
3421
CHACHBCHL) and 18.3 (CH3CHU and CH3CHL); (found
7.4, CH3CH2); dC (100 MHz; CDCl3) 173.0 (NC@O),
153.1 (OC@O), 138.1 and 137.9 (2 · i-C; 2 · Ph), 128.7,2
128.6,2 128.3,3 127.01 and 125.62 (10 · CH; 2 · Ph), 68.7
3
3
MUNH4þ, 369.2þ169; C22H29N2O3 requires 369.2173 and
found MLNH4
,
371.2296; C22H27D2N2O3 requires
1
371.2298). By mass spectrometry, found syn-34: syn-[D2]-
34 ratio: 52:48. Proton NMR shift: negative isotopic shift
at 5.45 ppm (CHN) was 0.00975 ppm (3.90 Hz at
400 MHz). Carbon NMR shifts: (a) negative isotopic shift
at 138.2 ppm (i-C; Ph) was 0.0382 ppm (3.84 Hz at
100.6 MHz); (b) negative isotopic shift at 69.3 ppm
(CH2O) was 0.404 ppm (40.7 Hz at 100.6 MHz); (c) nega-
tive isotopic shift at 57.4 ppm (CHN) was 0.084 ppm
(8.45 Hz at 100.6 MHz).
(1C, quintet, JC,D = 22.9 Hz, CD2O), 57.4 (CHN), 51þ.0
(PhCH), 26.1 (CH2) and 11.9 (CH3) (found MNH4
329.1835; C19H21D2N2O3 requires 329.1832).
,
4.35. (4R,2S)-3-[2-(6-Methoxynaphthyl)propionyl]-4-phenyl-
oxazolidin-2-one syn-36
White solid; Rf [light petroleum/diethyl ether (1:1)] 0.17;
20
mp 110–115 ꢁC; ½aꢂD ¼ þ166:2 (c 1.5, CHCl3); dH (400
MHz; CDCl3) 7.65 (1H, d, J 8.6, CH; Ar), 7.55 (1H,
d, J 8.6, CH; Ar), 7.35 (1H, s, CH; Ar), 7.31–7.22 (2H,
m, 2 · CH; Ph), 7.18–7.11 (4H, m, 1 · CH; Ar, and
3 · CH; Ph), 6.95 (2H, d, J 7.3, 2 · CH; Ar), 5.44 (1H,
dd, J 8.9 and 5.3, CHN), 5.22 (1H, q, J 6.9, CHCO),
4.58 (1H, t, J 8.9, CHAHBO), 4.03 (1H, dd, J 8.9 and 5.3,
CHAHBO), 3.92 (3H, s, CH3O) and 1.48 (3H, d, J 6.9,
CH3CH); dC (100.6 MHz; CDCl3) 173.5 (NC@O), 157.5
(OC@O), 152.9 (i-CO; Ar), 138.2, 135.0, 133.6 and 128.6
(4 · i-C; Ar), 129.3, 128.7 and 128.3 (3 · CH; Ph), 127.1,
126.9, 126.3, 125.8, 118.8 and 105.4 (6 · CH; Ar), 69.4
(CH2O), 57.7 (CHN), 55.1 (OCH3), 43.7 (ArCH) and
18.6 (CH3) (found MH+, 376.1553; C23H22NO4 requires
376.1549).
4.32. Parallel kinetic resolution of equimolar amount of 4-
phenyl-oxazolidinone (R)-6 and 4-phenyl-5,5-dideuterio-
oxazolidinone (S)-[D2]-6 using pentafluorophenyl 2-phen-
ylbutyrate acid (R)-28 and pentafluorophenyl (6-methoxy-2-
napthyl)-2-phenylpropionate (S)-35
In the same way as oxazolidinone syn-31, n-BuLi (0.43 ml,
3 M in hexane, 1.3 mmol), oxazolidinone (R)-6 (0.103 g,
0.63 mmol), oxazolidinone (S)-[D2]-6 (0.104 g, 0.63 mmol),
pentafluorophenyl 2-phenylbutyrate (R)-28 (0.25 g,
0.76 mmol) and pentafluorophenyl (6-methoxy-2-napth-
yl)-2-phenylpropionate (S)-35 (0.3 g, 0.75 mmol) in THF
(10 ml), gave after purification by flash column chroma-
tography on silica gel eluting with light petroleum ether/
ether (7:3) a separable mixture of oxazolidinone (S,R)-
syn-36 (0.205 g, 87%) (ratio = (S,R)-syn-36: (R,R)-anti-32;
96:4), (R,R)-anti-32 (6 mg, ꢀ3%) and (R,S)-syn-[D2]-32
(150 mg, 77%) (ratio = (R,S)-syn-[D2]-32: (S,S)-anti-[D2]-
32; >98:2).
Acknowledgements
We are grateful to the EPSRC for studentships (to Y.Y.
and E.C.), The Royal Society and The University of Lon-
don Central Research Fund for their financial support (to
J.E.), Onyx Scientific Limited for a CASE AWARD (to
M.D.), Syngenta for a CASE AWARD (to S.C.) and the
EPSRC National Mass Spectrometry Service (Swansea)
for accurate mass determinations.
4.33. Characterisation for: (4R)-phenyl-3-(2R-phenylbutyr-
yl)-oxazolidin-2-one anti-32
White solid; Rf [light petroleum (40–60 ꢁC)/diethyl ether
20
(1:1)] 0.55; mp = 145–149 ꢁC; ½aꢂD ¼ ꢁ160:0 (c 0.74,
CHCl3); mmax (CHCl3)/cmꢁ1 2359 (CD), 1780 (C@O),
1703 (C@O) and 1600 (Ph); dH (250 MHz; CDCl3) 7.44–
7.21 (10H, m, 10 · CH; 2 · Ph), 5.28 (1H, dd, J 8.7 and
3.4, CHN), 4.88 (1H, t, J 7.5, PhCH), 4.49 (1H, br t, J
8.7, CHAHBO), 4.20 (1H, dd, J 8.7 and 3.4, CHAHBO),
1.95 (1H, double quintet, J 13.5 and 7.5, CHAHBCH3),
1.65 (1H, double quintet, J 13.5 and 7.5, CHAHBCH3)
and 0.73 (3H, t, J 7.5, CH3CH2); dC (62.9 MHz; CDCl3)
173.7 (NC@O), 153.4 (OC@O), 139.5 (i-C; Ph), 138.6 (i-
C; Ph), 129.1, 128.8, 128.7, 128.5, 127.3 and 125.8
(6 · CH; PhA and PhB), 69.4 (CH2O), 58.1 (CHN), 50.4
(PhCH), 27.7 (CH2Ph) and 12.0 (CH3) (found MH+,
310.1430; C19H20NO3 requires 310.1443).
References
1. Reetz, M. T.; Becker, M. H.; Klein, H. W.; Stockigt, D.
Angew. Chem., Int. Ed. 1999, 38, 1758–1761.
2. Eames, J.; Suggate, M. J. J. Label. Compd. Radiopharm. 2004,
47, 705–717.
3. Taji, H.; Watanabe, M.; Harara, N.; Naoki, H.; Ueda, Y.
Org. Lett. 2002, 4, 2699–2702.
4. For reviews see: (a) Eames, J. Angew. Chem., Int. Ed. 2000,
39, 885–890; (b) Eames, J. In Parallel Kinetic Resolutions. In
Organic Synthesis Highlights; VCH-Wiley, 2003; Vol. V,
Chapter 17 pp 151–164 (ISBN 3-527-30611-0 Wiley-VCH,
Weinheim); (c) Dehli, J. R.; Gotor, V. Chem. Soc. Rev. 2002,
31, 365–370; For additional reports see: (d) Vedejs, E.; Chen,
X. J. Am. Chem. Soc. 1997, 119, 2584–2585; (e) Vedejs, E.;
Rozners, E. J. Am. Chem. Soc. 2001, 123, 2428–2429; (f)
Davies, S. G.; Diez, D.; El Hammouni, M. M.; Garner, A. C.;
Garrido, N. M.; Long, M. J.; Morrison, R. M.; Smith, A. D.;
Sweet, M. J.; Withey, J. M. Chem. Commum. 2003, 2410–
2411; (g) Davies, S. G.; Garner, A. C.; Long, M. J.; Smith, A.
D.; Sweet, M. J.; Withey, J. M. Org. Biomol. Chem. 2004, 2,
3355–3362; (h) Davies, S. G.; Garner, A. C.; Long, M. J.;
Morrison, R. M.; Roberts, P. M.; Savory, E. D.; Smith, A.
D.; Sweet, M. J.; Withey, J. M. Org. Biomol. Chem. 2005, 3,
2762–2775.
4.34. (4S)-Phenyl-3-(2R-phenylbutyryl)-5,5-dideuterio-oxaz-
olidin-2-one syn-[D2]-32
White solid; Rf [light petroleum/diethyl ether (1:1)] 0.35;
20
mp 58–60 ꢁC; ½aꢂD ¼ ꢁ54:2 (c 4.6, CHCl3); dH (400 MHz;
CDCl3) 7.19–7.01 (6H, m, 6· CH; PhA and PhB), 7.03
(2H, m, 2 · CH, PhA), 6.81 (2H, dt, J 6.9 and 1.5,
2 · CH, PhB), 5.35 (1H, s, CHPh), 4.81 (1H, t, J 7.4,
CHCO), 1.94 (1H, dq, J 13.7 and 7.4, CHAHBCH3), 1.71
(1H, dq, J 13.7 and 7.4, CHAHBCH3) and 0.87 (3H, t, J

3422
E. Boyd et al. / Tetrahedron: Asymmetry 17 (2006) 3406–3422
5. Coumbarides, G. S.; Dingjan, M.; Eames, J.; Flinn, A.;
12. Some optical rotations were performed in dimethylsulfoxide
due to limited solubility in dichloromethane and chloroform
at high concentrations.
Northen, J.; Yohannes, Y. Tetrahedron Lett. 2005, 46, 2897–
2902.
6. Coumbarides, G. S.; Dingjan, M.; Eames, J.; Flinn, A.;
Motevalli, M.; Northen, J.; Yohannes, Y. Synlett 2006, 101–
105.
7. Dickmann, D. A.; Meyers, A. I.; Smith, G. A.; Gawley, R. E.
Organic Syntheses; Wiley: New York, 1990; Collect. Vol. VII,
p 530.
13. Nicolas, E.; Russell, K. C.; Hruby, V. J. J. Org. Chem. 1993,
58, 766–770.
14. Periasamy, M.; Sivakumar, S.; Reddy, M. N.; Padmaja, M.
Org. Lett. 2004, 6, 265–268.
15. Evans, D. A.; Sjogren, E. B. Tetrahedron Lett. 1985, 26,
3783–3786.
8. Liao, L.; Zhang, F.; Dmitrenko, O.; Bach, R. D.; Fox, J. M.
J. Am. Chem. Soc. 2004, 126, 4490–4491.
16. Pirkle, W. H.; Simmons, K. A. J. Org. Chem. 1983, 48, 2520–
2527.
9. For these particular D-labelled oxazolidinones, there is minor
isotopic contamination (ꢀ2%) from their corresponding non-
labelled derivatives. For example, (R)-22 has an isotopic
distribution of 267 (100%, M+), 268 (17.9%), 269 (2.1%), 270
(0.2%), 271 (0%), where the most intense peak is set to 100%.
For the related di-deuteriated oxazolidinone (S)-[D2]-22, the
isotopic distribution is 269 (100%, M+), 270 (17.9%), 271
(2.1%), 272 (0.2%) and 273 (0%). For additional information
on isotopic patterns see: http://winter.group.shef.ac.uk/
chemputer/isotopes.html.
17. Quagliato, D. A.; Andrae, P. M.; Matelan, E. M. J. Org.
Chem. 2000, 65, 5037–5042.
18. Kleschick, W. A.; Reed, M. W.; Bordner, J. J. Org. Chem.
1987, 52, 3168–3169.
19. Burns, B.; King, N. P.; Tye, H.; Studley, J. R.; Gamble, M.;
Wills, M. J. Chem. Soc., Perkin Trans. 1 1988, 1027–1038.
20. Kirby, G. W.; McGuigan, H.; McLean, D. J. Chem. Soc.,
Perkin Trans. 1 1985, 1961–1966.
21. Ho, P. T.; Ngu, K.-Y. J. Org. Chem. 1993, 58, 2313–2316.
22. Evans, D. A.; Weber, A. E. J. Am. Chem. Soc. 1986, 108,
6757–6761.
23. Wu, Y.; Shen, X. Tetrahedron: Asymmetry 2000, 11, 4359–
4363.
24. Shen, Y-M.; Duan, W.-L.; Shi, M. Eur. J. Org. Chem. 2004,
3080–3089.
25. Feroci, M.; Inesi, A.; Palombi, L.; Rossi, L.; Sotgiu, G.
J. Org. Chem. 2001, 66, 6185–6188.
10. Vedejs, E.; Daugulis, O. J. Am. Chem. Soc. 2003, 125, 4166–
4173.
11. (a) Guo, J.; Wu, J.; Siuzdak, G.; Flinn, M. G. Angew. Chem.,
Int. Ed. 1999, 38, 1755–1758; (b) Diaz, D. D.; Yao, S.; Finn,
M. G. Tetrahedron Lett. 2001, 42, 2617–2619; (c) Evans, M.
A.; Morken, J. P. J. Am. Chem. Soc. 2002, 124, 9020–
9021.