Synthesis of highly enantio-enriched α-amino acids by carboxylation of N-(α-lithioalkyl)oxazolidinones

Article abstract of DOI:10.1002/1099-0690(200004)2000:7<1297::AID-EJOC1297>3.0.CO;2-L

N-(α-Stannylalkyl)oxazolidinones can be obtained as a mixture of diastereomers in three steps from aldehydes with yields dependent on the R group of R-CHO. They can be transformed by a tin-lithium exchange to N-(α- lithioalkyl)oxazolidinones which equilibrate rapidly to one diastereomer. These compounds give rise, after carboxylation, to the diastereopure N-(α- carboxyalkyl)oxazolidinones. Transformation of the oxazolidinone moiety to a free amino group is accomplished by a Birch-type reduction. Using this method, L-methionine, L-alanine, L-leucine and L-homocysteine were obtained in good yields and ee = 92% to 95%. The short time required for the whole sequence makes this method ideal for synthesising 1-[¹¹C]amino acids.

Full text of DOI:10.1002/1099-0690(200004)2000:7<1297::AID-EJOC1297>3.0.CO;2-L

FULL PAPER
Synthesis of Highly Enantio-Enriched α-Amino Acids by Carboxylation of
N-(α-Lithioalkyl)oxazolidinones
[a]
[a]
[b]
[a]
´
Fabien Jeanjean, Guy Fournet,* Didier Le Bars, and Jacques Gore
Keywords: α-Amino acids / Asymmetric synthesis / Carboxylation / N-(α-Lithioalkyl)oxazolidin-2-ones / Isotopic labelling
N-(α-Stannylalkyl)oxazolidinones can be obtained as a mix-
ture of diastereomers in three steps from aldehydes with
yields dependent on the R group of R–CHO. They can be
transformed by a tin-lithium exchange to N-(α-lithioalkyl)ox-
azolidinones which equilibrate rapidly to one diastereomer.
tion of the oxazolidinone moiety to a free amino group is
accomplished by a Birch-type reduction. Using this method,
L-methionine, L-alanine, L-leucine and L-homocysteine were
obtained in good yields and ee = 92% to 95%. The short time
required for the whole sequence makes this method ideal for
These compounds give rise, after carboxylation, to the dia- synthesising 1-[11C]amino acids.
stereopure N-(α-carboxyalkyl)oxazolidinones. Transforma-
Introduction
ing this approach are concerned mainly with the synthesis
of N-alkylated α-amino acids: (R)-Boc-proline from N-Boc-
pyrrolidine (ee 88%),[4] (R)-Boc-phenylsarcosine from N-
Boc-methylbenzylamine (ee 81%).[5] To our knowledge, the
only enantioselective carboxylation of an α-amino lithium
reagent giving access to α-amino esters with a primary
amino group was described by Duhamel et al. These au-
thors formed the organometallic species by deprotonation
of a benzylimine using a chiral lithium amide to obtain es-
ters of phenylglycine with an ee of up to 40%.[6]
This paper describes the synthesis of several enantiopure
α-amino acids by carboxylation of N-(α-lithioalkyl)oxazoli-
dinone reagents obtained by the tin-lithium exchange of the
corresponding N-(α-stannylalkyl)oxazolidinones 1 (Fig-
ure 2). This method, originally designed, carried out and
optimised for the preparation of -methionine,[7] was ex-
tended to other amino acids. When this preparative se-
quence was used as such, it was found that yields were very
dependent on the R group of the target amino acid.
There is a continued interest in the synthesis of enantio-
pure α-amino acids and many approaches have been de-
voted to this problem.[1] If the four possible bond discon-
nections a–d (Figure 1) are considered, the majority of stud-
ies are concerned either with the formation of the carbon–
R bond a (mainly by enantioselective alkylation of a glycine
derivative) or with that of the carbon–hydrogen bond b
(more often by catalytic hydrogenation of an α-keto acid
enamine). Comparatively, the methods involving the forma-
tion of the carbon–nitrogen bond c (electrophilic amination
of an ester enolate equivalent) are far less frequent and only
a few reports have described the formation of the carbon–
CO2H bond d.
Figure 1
In this last category, the Strecker reaction[2] is probably
the one most widely used; the key step relies on the nucleo-
philic addition of a cyanide to the CϭN bond of an imine,
the nitrile functionality being converted into the carboxylic
acid, generally by acid hydrolysis. Some asymmetric ver-
sions of this reaction have been described giving α-amino
acids with enantiomeric excesses of up to 99%.[3] However,
in this context, the simplest method would appear to be the
direct carboxylation of an α-amino organometallic species.
Surprisingly, the few studies which have been performed us-
Figure 2
Results and Discussion
Synthesis of l-Methionine
The aim of this work was the development of a synthetic
method for -methionine which would be able to produce
this amino acid labelled with 11C on the carboxyl group (-
1-[11C]methionine) for utilisation in Positron Emission To-
mography (PET).[8] Since this amino acid is inter alia in-
volved in protein synthesis, particularly in the human brain,
PET imaging using the labelled compound is a tool for
localising a tumour and monitoring its development. Pres-
[a]
´
Laboratoire de chimie organique 1, associe au CNRS, bat. 308
´
(CPE), Universite Claude Bernard Lyon I,
43, bd du 11 novembre 1918, 69622 Villeurbanne cedex, France
Fax: (internat.) ϩ 33-4/72431214
E-mail: fournet@univ-lyon1.fr
[b]
CERMEP,
59 bd Pinel, 69003 Lyon, France
Eur. J. Org. Chem. 2000, 1297Ϫ1305
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0407Ϫ1297 $ 17.50ϩ.50/0
1297

F. Jeanjean, G. Fournet, D. Le Bars, J. Gore
FULL PAPER
ently, -[11CH3]methionine is used routinely for this pur- The same reaction performed with 1ab also gave 6ab with
pose but, as a part of the metabolism of -methionine in- complete diastereoselectivity (yield 78%). It is noteworthy
volves the transfer of the methyl group to nucleic acids and that this diastereoselectivity can be obtained using as start-
lipids,[9] there is some imprecision in the amounts actually ing product the diastereomeric mixture of 1aa and a trans-
going into protein and this subsequently perturbs the inter- metallation step lasting only 5 min. This contrasts with the
pretation of PET results. It was therefore evident that results obtained in a preliminary study where the pure dia-
[11C]methionine labelled on a carbon atom other than the stereomers of 1aa isolated by silica gel chromatography
methyl group was needed. In addition, as 11CO2 is directly were first transmetallated by nBuLi at –78 °C and then
produced by the cyclotron, it appeared then that the most treated with tributyltin chloride. Under these conditions,
useful tool for PET could be -1-[11C]methionine formed and regardless of the transmetallation time, one diastereo-
by the carboxylation of an α-amino organometallic reagent mer, anticipated to be 1aaα was recovered in pure form
(Scheme 1).This project therefore had two criteria to fulfil: and was identical to the starting material, while the other
(i) high enantioselective synthesis in good yields of -1- diastereomer 1aaβ needed 30 min before the introduction of
[11C]methionine, and (ii) short synthesis times (less than the electrophile Bu3SnCl in order to be completely trans-
40 min) because the half life of [11C] is 20.4 min.
formed to 1aaα. It should be noted, though, that when the
transmetallation of 1aaβ was carried out in 5 min a mixture
of 1aaβ (40%) and 1aaα (60%) is obtained (Scheme 3).
These results verified the hypothesis of Pearson et al.,[12]
showing that the two diastereomeric α-aminolithio derivat-
ives are in an equilibrium which is displaced towards the α-
isomer because there is less steric interaction between the
phenyl group and the methylthioethyl substituent. The fast
displacement of this equilibrium in the presence of CO2
showed also that the carboxylation of the α-isomer of the
lithio species proceeded faster that than of the β one. Fi-
nally, as the pure acid 6aa was transformed into -methio-
nine (see below), the α configuration was also attributed to
this intermediate with the implication that the carbox-
ylation occurs with retention of configuration (Scheme 3).
Scheme 1
As previously reported,[7] the α-amino lithio derivative
was selected since it can be obtained either by direct depro-
tonation of nitrogen precursors of the amino group (for ex-
ample isocyanide 2)[10] or by heteroatom to lithium ex-
change using principally α-aminostannanes. The enantiose-
lective deprotonation of 2 by nBuLi/sparteine[11] being com-
pletely unsuccessful, the tin–lithium exchange was used,
taking advantage of the results of Pearson et al.[12] who ob-
tained diverse amino derivatives with good diastereoselec-
tivity using organolithium species obtained from enantio-
pure oxazolidinones 1.[13] The required compounds 1aa and
1ab (1:1 mixture of diastereomers) were prepared as de-
picted in Scheme 2 from 3-methylthiopropanal.
Scheme 3
For comparison, the diastereomers 6aaα and 6aaβ were
prepared as shown in Scheme 4 by a Strecker-type sequence
where the carboxy functionality was obtained by acid hy-
drolysis of a nitrile. Fortunately, the two diastereomers of
the nitrile 7 were separable by silica gel chromatography
and hydrolysed with an important retention of configura-
tion giving the acids 6aaα and 6aaβ. The configuration of
Scheme 2. Reagents and conditions: (a) Bu3SnLi, THF –78° C
(85%); (b) CBr4/PPh3 CH2Cl2 –70° C to room temp. (94%); (c)
NaH, DMF room temp. then 4a (1aa: 90%; 1ab: 87%); (d) nBuLi,
THF –78 °C then CO2 bubbling
The treatment of 1aa with one equivalent of nBuLi in these acids was verified after their conversion into enantio-
1
THF at –78 °C followed by carboxylation by gaseous CO2 mers of methionine. The comparison of their H and 13C
and acid work up led, in less than 15 min, to the oxazol- NMR spectra showed unambiguously the total diastereose-
idino acid 6aa as a single diastereomer with a yield of 85%. lectivity of the carboxylation process depicted in Scheme 3.
1298
Eur. J. Org. Chem. 2000, 1297Ϫ1305

Synthesis of Highly Enantio-Enriched α-Amino Acids
FULL PAPER
chemical yield of 15–25%.[16] Once the optimisation for the
routine preparation of labelled compound been accomp-
lished, full details will be published elsewhere.[17]
Extension of the Method to the Synthesis of Other
α-Amino Acids
In view of the good results (high yield, and stereoselectiv-
ity) observed in the preparation of pure -methionine by
direct carboxylation of a N-(α-lithioalkyl)oxazolidinone we
tried to determine whether a similar approach could be
used for the synthesis of some other α-amino acids such
as -leucine, -alanine, -homocysteine, -phenylalanine, -
valine and -serine (Figure 3).
Scheme 4. Reagents and conditions: (a) NaCN, MeOH reflux
(67%); (b) triphosgene , Et3N, CH2Cl2 room temp. (89%); (c) SiO2
chrom. separation; (d) HCl 12 , 55° C. (90%)
Figure 3. R ϭ CH2CHMe2 (leucine), Me (alanine), iPr (valine),
CH2CH2SH (homocysteine), Bzl (phenylalanine), CH2OH (serine)
The N-(α-stannylalkyl)oxazolidinones 1a were prepared
by the sequence depicted for -methionine (Scheme 2) start-
ing from the corresponding commercially available alde-
hydes RCHO (Scheme 5), with the exception of 3-benzylthi-
opropanal which was prepared by the reaction of benzyl
thiol with acrolein.[18] For each step, the experimental con-
ditions of the methionine sequence were used, with the ex-
ception of the bromination (step 2) where, for reasons of
easier purification, Ph3P–Br2 was used instead of PPh3–
CBr4 in the case of entries 1,2 and 4 of Table 1. As can be
seen in this table, the yields of each step depend on the
nature of R and are generally lower than those observed for
the methionine sequence.
Finally, the chiral auxiliary of 6aa and 6ab had to be
removed in a short time and by a mild procedure which
permitted the conservation of the configurational integrity
of the stereogenic carbon previously formed. The first
method used for transforming the oxazolidino group to the
corresponding primary amine was the palladium-ammo-
nium formate hydrogenolysis.[14] As could be anticipated,
this reaction was unsuccessful with 6aa, but 6ab was depro-
tected in less than 15 min by running the reaction in re-
fluxing methanol. Unfortunately, the separation of me-
thionine from excess formate proved to be difficult and took
too long for our purpose. On the contrary, a Birch–Evans
protocol[14] using lithium in liqu. NH3 in the presence of
tBuOH/THF at –78 °C, followed by a fast ion exchange
chromatography transformed 6aa in 15 min to -methionine
with an 85% yield. The analysis of this α-amino acid by
chiral HPLC [column: chirobiotic T astec , elution with
EtOH/H2O (60:40) at 1 mL/min] showed its enantiopurity
and permitted its identification with -methionine by its re-
tention time of 5.2 min (under the same conditions, -me-
thionine has a tR of 8.06 min).
These results show that the totally enantioselective pre-
paration of -methionine can be done by carboxylation of
an enantiopure N-(α-lithioalkyl)oxazolidinone; the entire
process requires 35–40 min and is consequently suitable for
the preparation of -1-[11C]methionine. The preparation of
Scheme 5
Again, the transformation of the N-(α-stannylalkyl)ox-
the labelled compound has already been done with a radio- azolidinones was accomplished using the same conditions
Table 1
R
Target -amino acid
Step 1
[%]
Step 2
[%]
Step 3
[%]
Overall yield
[%]
iBu
leucine
3b [64]
3c [44]
3d [52]
3e [45]
3f [64]
3g [35]
4b [57]
4c [42]
4d [70]
4e [80]
4f [31]
4g [53]
1b [84]
1c [71]
1d [90]
1e [10]
1f [Ͻ 5]
1g [55]
30.5
13
Me
alanine
BzlS(CH2)2
Bzl
homocysteine
phenyl alanine
valine
33
3.6
ഠ 1
10
nPr
BzlOCH2
serine
Eur. J. Org. Chem. 2000, 1297Ϫ1305
1299

F. Jeanjean, G. Fournet, D. Le Bars, J. Gore
FULL PAPER
as those which were successful for the transformation of 11C (the main purpose of this study) but also with 13C
1aa to -methionine. As yields of the synthesis of the α- and 14C.
stannyloxazolidinones 1 varied with the R substituent, at-
tempts at enantioselective preparation of the corresponding
α-amino acids were made only on 1b, 1c, 1d, and 1g. The
results are listed in Table 2.
Experimental Section
General Remarks: All procedures were conducted in oven dried
glassware under positive nitrogen pressure and using syringe-needle
transfer techniques. DMF and iPr2NH were distilled from CaH2,
THF from sodium/benzophenone. – 1H (200 MHz or 300 MHz)
and 13C NMR (50 MHz or 75 MHz) spectra were recorded on a
Bruker AC 200 or AM 300. Chemical shifts are reported as δ values
Table 2
starting
material
6
amino acid
ee
[%]
[%]
1b
1c
1d
1g
6b [85]
6c [72]
6d [80]
6g [0]
-leucine
-alanine
-homocysteine
Ϫ
95
95
92
Ϫ
1
relative to the solvent peak of CHCl3 set to 7.26 for H and 77.16
for 13C. 19F NMR spectra were recorded at 188 MHz on a Bruker
AC 200 with CFCl3 as internal standard. – IR spectra were carried
out on a Perkin–Elmer 298 spectrophotometer. – Melting points
were determined in open capillaries and are uncorrected. – Optical
In the first three cases, the yields are good and the ex- rotation values were determined using a Perkin–Elmer 241 polari-
meter. – Flash chromatography (FC) were performed using Merck
60 (40–63 µm) silica. – Mass spectra were recorded on a Nermag
R-10–10S (70 eV). – Elemental analyses were performed at the SCA
Solaize (France). – Oxazolidinones 5a and 5b were prepared from
their corresponding amino alcohols by using triphosgene .[20]
pected α-amino acid is obtained with a high enantiomeric
excess (Scheme 6). Unfortunately the oxazolidino acid 6g
could not be obtained. In this last case, we observed loss of
the starting stannane (TLC) only when three equivalents of
butyllithium were used; this excess of butyllithium, however,
resulted in the formation after carboxylation of a complex Preparation of α-Hydroxyorganostannanes
mixture from which it was impossible to isolate the ex-
pected 6g.
1-Tributylstannyl-3-methylthio Propan-1-ol (3a): To iPr2NH
(0.93 mL, 6.6 mmol) in THF (7 mL) was added dropwise n-butylli-
thium (2.5  hexane solution, 6.6 mmol) at 0 °C. The solution was
stirred for 15 min and Bu3SnH (1.77 ml, 6.6 mmol) was added dur-
ing 5 min. After 30 min, the reaction mixture was chilled to –78°
C and a solution of 3-methylthiopropanal (0.66 mL, 6.6 mmol) in
THF (3 mL) was added dropwise. After stirring for an additional
30 min the mixture was warmed to room temp., quenched with
saturated ammonium chloride (30 mL) and extracted with Et2O (3
ϫ 15 mL). The combined organic phases were washed with brine
(3 ϫ 40 mL), dried (Na2SO4) and concentrated. Purification of the
crude product by FC (petroleum ether then petroleum ether/Ac-
OEt ϭ 90:10) gave pure 3a (2.21 g, 85%) as an oil. – IR (film): ν˜ ϭ
Scheme 6
The amino acids were purified on an ion-exchange resin
(Dowex 50 W-X8) and identified by 1H NMR spectroscopy
in D2O/DCl by comparison with commercial samples. Their
optical purity was determined from the 19F NMR spectra
of their Mosher amides prepared in a conventional manner
from the methyl esters;[19] the nature of the isolated enanti-
omer and the enantiomeric excess were determined by com-
parison with the spectra of nonracemic mixtures of the cor-
responding Mosher amides prepared from commercially
available - and -amino acids – the racemic homocysteine
was used. In the case of leucine, only the -isomer was de-
tected while for alanine and homocysteine, both enantio-
mers were present with a large predominance of the  iso-
mer.
1
3320, 2840, 1470 cm–1. – H NMR (CDCl3, 200 MHz): δ ϭ 0.85–
0.95 (m, 15 H), 1.25–1.60 (m, 12 H), 1.95 –2.10 (m, 2 H), 2.10 (s,
3 H), 2.65 (t, J ϭ 7 Hz, 2 H), 4.20–4.25 (m, 1 H). – 13C NMR
(50 MHz): δ ϭ 8.6 (CH2, Bu3Sn), 13.7 (CH3, Bu3Sn), 15.5 (CH3),
27.5 (CH2, Bu3Sn), 29.2 (CH2, Bu3Sn), 32.6 (CH2), 36.8 (CH2),
67.4 (CH). – EI MS; m/z (%): 313 (6), 279 (8), 269 (6), 177 (7), 64
(100), 63 (20), 57 (18), 55 (14), 47 (31), 45 (19). 41 (12).
3-Methyl-1-(tributylstannyl)butan-1-ol (3b): Prepared as described
for 3a from isovaleraldehyde (18 mmol). Purification by FC (petro-
leum ether then petroleum ether/AcOEt 90:10), colourless oil, yield
1
64%. – IR (film): ν˜ ϭ 3400, 1460, 1375 cm–1. – H NMR (CDCl3,
300 MHz): δ ϭ 0.95–1.05 (m, 21 H), 1.22–1.38 (m, 7 H), 1.45–1.58
(m, 6 H), 1.75–1.88 (m, 2 H), 4.19 (m, 1 H). – 13C NMR (CDCl3,
75 MHz): δ ϭ 8.4 (CH2, Bu3Sn), 13.7 (CH3, Bu3Sn), 21.7 (CH3),
23.5 (CH3), 25.0 (CH), 27.5 (CH2, Bu3Sn), 29.3 (CH2, Bu3Sn), 47.5
(CH2), 66.4 (CH).
As for methionine, the entire process giving the amino
acid from 1 can be run in 35–40 min, which should allow
the implementation of this method for the preparation of
enantiopure 1-[11C]natural or unnatural α-amino acids.
1-(Tributylstannyl)ethan-1-ol (3c): Prepared as described for 3a
from acetaldehyde (18 mmol). Purification by FC (petroleum ether
then petroleum ether/AcOEt ϭ 90:10), colourless oil, yield 44%. Ϫ
IR (film): ν˜ ϭ 3320, 1455 cm–1. – 1H NMR (CDCl3, 300 MHz):
δ ϭ 0.87–0.95 (m, 15 H), 1.23–1.53 (m, 12 H), 1.58–1.67 (m, 3 H),
2.20 (d, J ϭ 2.6 Hz, 1 H), 4.16 (q, J ϭ 7.5 Hz, 1 H). – 13C NMR
(CDCl3, 300 MHz):δ ϭ 8.3 (CH2, Bu3Sn), 13.7 (CH3, Bu3Sn), 24.5
Conclusion
In conclusion, the results presented here show that the
carboxylation of N-(α-lithioalkyl)oxazolidinones provides a
new method for obtaining enantiopure α-amino acids with
the possibility of labelling the carboxyl group not only by (CH3), 27.5 (CH2, Bu3Sn), 29.4 (CH2, Bu3Sn), 63.6 (CH).
1300 Eur. J. Org. Chem. 2000, 1297Ϫ1305

Synthesis of Highly Enantio-Enriched α-Amino Acids
FULL PAPER
3-(Benzylthio)-1-(tributylstannyl)propan-1-ol (3d): Prepared as de-
scribed for 3a from 3-(benzylthio) propanal[17] (9.5 mmol). Puri-
fication by FC (petroleum ether then petroleum ether/AcOEt
1-Bromo-3-methyl-1-(tributylstannyl)butane (4b): To triphenylphos-
phane (0.695 g, 2.65 mmol) in CH2Cl2 was added at 0 °C 2.75 mL
of a 0.97  bromine solution in CH2Cl2. To the white suspension
of the PPh3 Br2 complex was added dropwise a solution of the hy-
90:10), colourless oil, yield 52% – IR (film): ν˜ ϭ 3400, 3080, 3060,
1
3020 cm–1. – H NMR (CDCl3, 300 MHz): δ ϭ 0.88–1.02 (m, 15 droxystannane 3b in CH2Cl2 (2.7 mL). The reaction mixture was
H), 1.27–1.52 (m, 12 H), 2.01–2.12 (m, 2 H), 2.40–2.60 (m, 2 H) warmed to room temp. and stirred for 4 h. Solvent was removed
3.70 (s, 2 H), 4.20 (dd, J ϭ 3.9 Hz, J ϭ 9.6 Hz, 1 H), 7.26–7.42 (m,
under reduced pressure and the residue was purified by FC (petro-
5 H). – 13C NMR (CDCl3, 50 MHz): δ ϭ 8.7 (CH2 Bu3Sn), 13.8 leum ether). Pure 4b (0.67 g, 57%) was obtained as a colourless
(CH3, Bu3Sn), 27.6 (CH2, Bu3 Sn), 26.7 (CH2), 29.3 (CH2, Bu3Sn), oil. – IR (film): ν˜ ϭ 1470, 1380 cm–1. – 1H NMR (CDCl3,
36.5 (CH2), 37.2 (CH2) 67.3 (CH), 127.1 (CH), 128.6 (CH) 128.9 300 MHz): δ ϭ 0.85–1.05 (m, 21 H), 1.28–1.38 (m, 6 H), 1.48–1.64
(CH), 138.5 (C).
(m, 7 H), 1.89Ϫ2.10 (m, 2 H), 3.72 (dd, J ϭ 4.25 Hz, J ϭ 11.95 Hz,
1 H). – 13C NMR (CDCl3, 50 MHz): δ ϭ 9.8 (CH2, Bu3Sn), 13.7
(CH3, Bu3Sn), 20.6 (CH3), 23.1 (CH3), 26.9 (CH), 27.5 (CH2,
Bu3Sn), 29.0 (CH2, Bu3Sn), 37.3 (CH), 46.7 (CH2).
2-Phenyl-1-(tributylstannyl)ethanol (3e): Prepared as described for
3a from phenylacetaldehyde (18 mmol). Purification by FC (petro-
leum ether, then petroleum ether/AcOEt 90:10), colourless oil, yield
45%. Ϫ IR (film): ν˜ ϭ 3400, 3080, 3040, 3020, 1455, 750, 700 cm–1. 1-Bromo-1-(tributylstannyl)ethane (4c): Prepared as described for 4b
–
1H NMR (CDCl3, 300 MHz): δ ϭ 0.87Ϫ0.97 (m, 15 H),
starting from 3c (12.6 mmol). Purification by FC (petroleum ether),
colourless oil, yield 42%. – IR (film): ν˜ ϭ 1470, 1380, 1120, 1000
cm–1. – 1H NMR (CDCl3, 300 MHz): δ ϭ 0.85–1.00 (m, 15 H),
1.27–1.40 (m, 6 H), 1.48–1.57 (m, 6 H), 1.92 (d, J ϭ 7.7 Hz, 3 H),
3.69 (q, J ϭ 7.7 Hz, 1 H). Ϫ 13C NMR (CDCl3, 50 MHz): δ ϭ 9.7
(CH2, Bu3Sn), 13.8 (CH3, Bu3Sn), 25.0 (CH3), 27.5 (CH2, Bu3Sn),
29.0 (CH2, Bu3Sn), 32.4 (CH).
1.27Ϫ1.57 (m, 12 H), 3.04 (m, 2 H), 3.7 (d, J ϭ 2.2 Hz, 1 H), 4.21
(dd, J ϭ 6.1 Hz, J ϭ 9 Hz, 1 H), 7.21–7.37 (m, 5 H). – 13C NMR
(CDCl3, 50 MHz): δ ϭ 8.7 (CH2, Bu3Sn), 13.8 (CH3, Bu3Sn), 27.5
(CH2, Bu3Sn), 29.3 (CH2, Bu3Sn), 44.5 (CH2), 68.7 (CH), 126.5
(CH), 128.6 (CH), 129.1 (CH), 139.9 (C).
2-Methyl-1-(tributylstannyl)propan-1-ol (3f): Prepared as described
for 3a starting from 2-methyl propanal (18 mmol). Purification by
FC (petroleum ether then petroleum ether/AcOEt 90:10), colour-
3-(Benzylthio)-1-bromo-1-(tributylstannyl)propane (4d): Prepared as
described for 4a starting from 3d (6 mmol). Purification by FC
less oil, yield 64%. Ϫ IR (film): ν˜ ϭ 3300, 1475, 1390 cm–1. Ϫ 13C (petroleum ether), colourless oil, yield 70%. Ϫ IR (film): ν˜ ϭ 3080,
NMR (CDCl3, 50 MHz): δ ϭ 9.3 (CH2, Bu3Sn), 13.6 (CH3, 3040, 1610, 1590, 1380, 970, 720 cm–1. – 1H NMR (CDCl3,
Bu3Sn), 17.3 (CH3), 19.8 (CH3), 27.5 (CH2, Bu3Sn), 29.3 (CH2,
Bu3Sn), 35.5 (CH), 76.4 (CH).
300 MHz): δ ϭ 0.82–0.97 (m, 15 H) 1.22–1.57 (m, 12 H), 2.10–2.32
(m, 2 H), 2.52–2.75 (m, 2 H), 3.70 (dd, J ϭ 3.9 Hz, J ϭ 9.6 Hz, 1
H), 3.72 (s, 2 H), 7.26–7.32 (s, 5 H). – 13C NMR (CDCl3, 75 MHz):
δ ϭ 10.0 (CH2, Bu3Sn), 13.8 (CH3, Bu3Sn), 27.5 (CH2, Bu3Sn),
29.0 (CH2, Bu3Sn), 31.5 (CH2), 36.6 (CH2), 37.0 (CH), 37.5 (CH2),
127.1 (CH), 128.6 (CH), 128.9 (CH) 138.6 (C).
2-Benzyloxy-1-(tributylstannyl)ethan-1-ol (3g): Prepared as de-
scribed for 3a from 2-benzyloxy ethanal (5.9 mmol). Purification
by FC (petroleum ether then petroleum ether/AcOEt 90:10), col-
ourless oil, yield 35%.Ϫ IR (film): ν˜ ϭ 3350, 3070, 3030 cm–1. –
1H NMR (CDCl3, 300 MHz): δ ϭ 0.78–0.90 (m, 15 H), 1.22–1.58 1-Bromo-2-phenyl-1-(tributylstannyl)ethane (4e): Prepared as de-
(m, 12 H), 2.16 (d, J ϭ 4.8 Hz, 1 H, OH), 3.76 (d, J ϭ 5.15 Hz, 2
scribed for 4a starting from 3e (18 mmol). Purification by FC (pe-
H), 4.23 (dd, J ϭ 4.8, 5.15 Hz, 1 H), 4.52 (d, JAB ϭ 11.52 Hz, 1 troleum ether), colourless oil, yield 45%. – IR (film): ν˜ ϭ 3060,
1
H), 4.58 (d, JAB ϭ 11.52 Hz, 1 H) 7.25–7.36 (m, 5 H). – 13C NMR 3020 cm–1. – H NMR (CDCl3, 300 MHz): δ ϭ 0.80–0.97 (m, 15
(CDCl3, 75 MHz): δ ϭ 8.8 (CH2, Bu3Sn), 13.7 (CH3, Bu3Sn), 27.5
(CH2, Bu3Sn), 29.2 (CH2, Bu3Sn), 67.7 (CH), 72.9 (CH2), 76.2
(CH2), 127.7 (CH), 127.8 (CH), 128.4 (CH), 138.3 (c).
H), 1.22–1.50 (m, 12 H), 3.30 (dd, J ϭ 7.73, AB ϭ 13.98 Hz, 1 H),
3.37 (dd, J ϭ 8.82 Hz, JAB ϭ 13.98 Hz, 1 H), 3.80 (dd, J ϭ 7.73 Hz,
J ϭ 8.82 Hz, 1 H), 7.22–7.37 (m, 5 H). – 13C NMR (CDCl3,
75 MHz): δ ϭ 10.2 (CH2, Bu3Sn), 13.8 (CH3, Bu3Sn), 27.5 (CH2,
Bu3Sn), 29.0 (CH2, Bu3Sn), 38.2 (CH), 44.3 (CH2), 126.9 (CH),
128.5 (CH), 128.9 (CH), 140.6 (C).
Preparation of α-Bromo Organostannanes
1-Bromo-3-(methylthio)-1-(tributylstannyl)propane (4a): A solution
of triphenylphosphane (1.3 g, 4.96 mmol) in CH2Cl2 (7 mL) was
added at –78 °C to the alkoxystannane 3a (1.037 g, 2.62 mmol)
in CH2Cl2 (8 mL), then a solution of tetrabromomethane (2.33 g,
7.03 mmol) in CH2Cl2 (7 mL) was introduced dropwise. The reac-
tion mixture was stirred for 1 h at –78 °C and warmed slowly to
room temp within ca. 2 h. The solvent was removed by evaporation
and the residue was filtered on a short column of silica gel eluting
with CH2Cl2. Solvent was removed and the crude product was puri-
fied by FC (petroleum ether) to give pure 4a (1.13 g, 94%) as a
1-Bromo-2-methyl-1-(tributylstannyl)propane (4f): Prepared as de-
scribed for 4b starting from 3f (6.8 mmol). Purification by FC (pe-
troleum ether), colourless oil, yield 31%. Ϫ IR (film): ν˜ ϭ1470
cm–1. Ϫ 1H NMR (CDCl3, 300 MHz): δ ϭ 0.85–1.10 (m, 21 H), 1.25–
1.60 (m, 12 H), 2.05–2.15 (m, 1 H), 3.68 (d, J ϭ 4.78 Hz, 1 H). –
13C NMR (CDCl3, 50 MHz): δ ϭ 10.8 (CH2, Bu3Sn), 13.7 (CH3,
Bu3Sn), 22.2 (CH3), 23.0 (CH3), 27.5 (CH2, Bu3Sn), 29.0 (CH2,
Bu3Sn), 34.8 (CH), 50.4 (CH).
colourless oil. – IR (film): ν˜ ϭ 1470, 1380 cm–1. – 1H NMR 2-Benzyloxy-1-bromo-1-(tributylstannyl)ethane (4g): Prepared as
(CDCl3, 200 MHz): δ ϭ 0.90–0.97 (m, 15 H), 1.30–1.6 (m, 12 H), described for 4a starting from 3g (3.7 mmol). Purification by FC
2.10 (s, 3 H), 2.10–2.25 (m, 2 H), 2.55–2.85 (m, 2 H), 3.75 (dd, J ϭ (petroleum ether), colourless oil, yield 53%. – IR (film): ν˜ ϭ 3060,
5.45 Hz, J ϭ 9.1 Hz, 1 H). – 13C NMR (CDCl3, 50 MHz): δ ϭ
10.2 (CH2, Bu3Sn), 13.8 (CH3, Bu3Sn), 15.7 (CH3), 27.5 (CH2, H), 1.25 Ϫ 1.54 (m, 12 H), 3.73 (t, J ϭ 5.88 Hz, 1 H), 3.94 (d, J ϭ
Bu3Sn), 29.1 (CH2, Bu3Sn), 34.3 (CH2), 36.9 (CH2), 37.6 (CH). – 5.88 Hz, 2 H), 4.55 (d, JAB ϭ 11.55 Hz, 1 H), 4.60 (d, JAB
EI-MS; m/z (%): 403 (15), 401 (24), 399 (20), 323 (21), 321 (18), 11.55 Hz, 1 H), 7.27–7.36 (m, 5 H). – 13C NMR (CDCl3, 75 MHz):
313 (31), 311 (18), 289 (7), 257 (11), 235 (15), 127 (29), 119 (10), δ ϭ 10.3 (CH, Bu3Sn), 13.7 (CH3, Bu3Sn), 27.4 (CH2 Bu3Sn), 28.9
61 (100), 57 (72), 41 (81). – C16H35BrNSSn (458.13): calcd. C 41.95, (CH2, Bu3Sn), 35.7 (CH), 72.8 (CH2), 74.9 (CH2), 127.7 (CH),
3020 cm–1. – H NMR (CDCl3, 300 MHz): δ ϭ 0.85–1.10 (m, 15
1
ϭ
H 7.70; found C 41.96, H 7.89.
127.8 (CH), 128.4 (CH), 138.1 (C).
Eur. J. Org. Chem. 2000, 1297Ϫ1305
1301

F. Jeanjean, G. Fournet, D. Le Bars, J. Gore
FULL PAPER
Preparation of N-(α-Stannylalkyl)oxazolidinones
4.86 (d, J ϭ 8.4 Hz, 1 H), 5.77 (d, J ϭ 8.4 Hz, 1 H), 6.9–7.03 (m,
10 H). – 13C NMR (CDCl3, 50 MHz): δ ϭ 10.3 (CH2, Bu3Sn), 13.4
(CH2, Bu3Sn), 14.6 (CH3), 27.2 (CH2, Bu3Sn), 28.8 (CH2, Bu3Sn),
31.2 (CH2) 32.2 (CH2), 44.3 (CH), 67.9 (CH), 78.9 (CH), 125.5
(CH), 127.3 (CH), 127.5 (CH), 127.8 (CH), 128.2 (CH), 128.3
(CH), 134.8 (C), 135.0 (C), 158.2 (C), 170.6 (C).
(4S,1ЈR)-3-[3-(Methylthio)-1-(tributylstannyl)propyl]-4-phenyloxa-
zolidin-2-one (1aaα) and (4S,1ЈS)-3-[3-(Methylthio)-1-(tributylstan-
nyl)propyl]-4-phenyloxazolidin-2-one (1aaβ): Sodium hydride
(72 mg, 60% dispersion in oil, 1.8 mmol) was added at room temp.
to a solution of (S)-4-phenyloxazolidin-2-one (0.24 g, 1.47 mmol)
in DMF (6 mL). The mixture was stirred for 30 min before adding
a solution of bromostannane 4a (0.825 g, 1.8 mmol) in DMF
(1.2 mL). After 4 h, water was carefully added to the mixture and
the solution was extracted with AcOEt (3 ϫ 25 mL). The combined
organic phases were washed with brine (3 ϫ 30 mL), dried over
Na2SO4 and concentrated under reduced pressure. The residue was
purified by FC (petroleum ether/AcOEt ϭ 90:10 then 80:20), a 1:1
mixture of diastereomers 1aaα/1aaβ was obtained as a colourless
oil (0.715 g, 90%). The two diastereomers were separated by FC
(petroleum ether/AcOEt ϭ 95:5).
(4S,1ЈR)-3-[3-Methyl-1-(tributylstannyl)butan-1-yl]-4-phenyloxa-
zolidin-2-one (1bα) and (4S,1ЈS)-3-[3-methyl-1-(tributylstannyl)bu-
tan-1-yl]-4-phenyloxazolidin-2-one (1bβ): Prepared as described for
1aa by alkylation of the sodium salt of (S)-4-phenyloxazolidium-2-
one with the bromostannane 4b (7.4 mmol). FC purification (petro-
leum ether/AcOEt 90:10) gave a 1:1 mixture of diastereomers 4bα
and 4bβ as a viscous oil, yield 84%. The two diastereomers are
separated by FC (petroleum ether ϭ 95/5).
1bα: [α]D ϭ ϩ23.05 (c ϭ 1.2, CHCl3). – IR (α ϩ β, film): ν˜ ϭ 3080,
3060, 3020, 1745 cm–1. – 1H NMR (CDCl3, 300 MHz): δ ϭ 0.78
(d, J ϭ 6.25 Hz, 3 H), 0.82–0.92 (m, 15 H), 1.22–1.50 (m, 16 H),
1.64–1.72 (m, 2 H), 2.71 (t, J ϭ 7.5 Hz, 1 H), 4.10 (dd, J ϭ 7.72,
JAB ϭ 8.8 Hz, 1 H), 4.59 (apparent t, J ϭ 9 Hz, 1 H), 4.83
(apparent t, J ϭ 8.3 Hz, 1 H), 7.26–7.42 (m, 5 H). – 13C NMR
(CDCl3, 75 MHz): δ ϭ 10.6 (CH2, Bu3Sn), 13.7 (CH3, Bu3Sn), 22.5
(CH3), 22.7 (CH3), 26.6 (CH), 27.5 (CH2, Bu3Sn) 29.1 (CH2,
Bu3Sn), 39.4 (CH), 40.8 (CH), 62.2 (CH), 69.4 (CH2), 127.4 (CH),
129.1 (CH), 129.2 (CH), 138.3 (C), 158.6 (C). – C26H45NO2Sn
(522.35): calcd. C 59.79, H 8.68; found C 60.00, H 8.93.
1aaα: [α]D ϭ ϩ22.9 (c ϭ 2.2, CHCl3). – IR (film): ν˜ ϭ 3080, 3060,
3040, 1740, 1605, 1590, 760, 700 cm–1. – 1H NMR (CDCl3,
300 MHz): δ ϭ 0.75–0.95 (m, 15 H), 1.15–1.50 (m, 12 H) 2.10 (s,
3 H), 1.85–2.15 (m, 2 H), 2.45 (t, J ϭ 7.0 Hz, 2 H) 2.75 (dd, J ϭ
5.99 Hz, J ϭ 6.61 Hz, 1 H), 4.15 (dd, J ϭ 7.35 Hz, J ϭ 8.82 Hz, 1
H), 4.60 (t, J ϭ 8.82 Hz, 1 H), 4.86 (dd, J ϭ 7.35 Hz, J ϭ 8.82 Hz,
1 H), 7.30–7.45 (m, 5 H). – 13C NMR (CDCl3, 50 MHz): δ ϭ 10.9
(CH2, Bu3Sn),13.7 (CH3, Bu3Sn), 27.4 (CH2, Bu3Sn), 29.0 (CH2,
Bu3Sn), 30.9 (CH2), 32.7 (CH2), 40.1 (CH), 61.5 (CH), 69.3 (CH2),
127.4 (CH2), 129.1 (CH2), 138.0 (C), 158.7 (C). – C25H43NO2SSn
(540.4): calcd. C 55.57, H 8.02; found C 55.96, H 8.16.
1bβ: Eluting first. – [α]D ϭ ϩ23.9 (c ϭ 2.4, CHCl3). – 1H NMR
(CDCl3, 300 MHz): δ ϭ 0.54 (d, J ϭ 6.6 Hz, 3 H), 0.58 (d, J ϭ
6.6 Hz, 1 H), 0.83–0.93 (m, 15 H), 1.24–1.50 (m, 13 H), 1.62–1.78
(m, 2 H), 2.84 (dd, J ϭ 6.98 Hz, J ϭ 9.19 Hz, 1 H), 4.21 (m, 1 H),
4.48–4.60 (m, 2 H), 7.34–7.40 (m, 5 H). – 13C NMR (CDCl3,
75 MHz): δ ϭ 10.2 (CH2, Bu3Sn), 13.7 (CH3, Bu3Sn), 21.9 (CH3),
22.6 (CH3), 25.8 (CH), 27.5 (CH2, Bu3Sn), 29.2 (CH2, Bu3Sn), 41.6
(CH2), 42.6 (CH), 63.2 (CH), 69.5 (CH2), 128.1 (CH), 129.1 (CH),
129.3 (CH), 138.4 (C), 158.4 (C). – C26H45NO2Sn (522.35): calcd.
C 59.79, H 8.68; found C 59.61, H 8.53.
1aaβ: Eluting first. – [α]D ϭ ϩ21.5 (c ϭ 2.3, CHCl3). – IR (film):
ν˜ ϭ 3080, 3060, 3040, 1740, 1605, 1590, 760, 700 cm–1. – 1H NMR
(CDCl3, 300 MHz): δ ϭ 0.80–0.95 (m, 15 H) 1.20–1.55 (m, 12 H),
1.79 (s, 3 H), 1.85–1.95 (m, 2 H), 2.10–2.20 (m, 2 H), 2.92 (apparent
t, J ϭ 7.6 Hz, 1 H), 4.24 (dd, J ϭ 5.52 Hz, J ϭ 6.61 Hz, 1 H),
4.48–4.62 (m, 2 H), 7.41 (m, 5 H). – 13C NMR (CDCl3, 50 MHz):
δ ϭ 10.4 (CH2, Bu3Sn), 13.6 (CH3, Bu3Sn), 14.8 (CH3), 27.4 (CH2,
Bu3Sn), 29.1 (CH2, Bu3Sn), 31.4 (CH2), 32.4 (CH2), 43.7 (CH) 63.4
(CH), 69.5 (CH2), 127.9 (CH), 129.1 (CH), 129.3 (CH), 138.4 (C),
158.6 (C). – C25H43NO2SSn (540.4): calcd. C 55.57, H 8.02; found
C 55.62, H 8.05.
(4S,1ЈR)-3-[1-(Tributylstannyl)ethyl]-4-phenyloxazolidin-2-one (1cα)
and (4S,1ЈS)-3-[1-(Tributylstannyl)ethyl]-4-phenyloxazolidin-2-one
(1cβ) Prepared as described for 1aa by alkylation of the sodium
salt of (S)-4-phenyloxazolidin-2-one with the bromostannane 4c.
Ϫ Scale 5.2 mmol. Ϫ A FC purification (petroleum ether/AcOEt ϭ
90/10) gave a 1/1 mixture of diastereomers 1cα and 1cβ as a viscous
oil, yield 71%. The two diastereomers were separated by FC (petro-
leum ether/ACOEt ϭ 95/5).
(4S,5R,1ЈR)-3-[3-(Methylthio)-1-(tributylstannyl)propyl]-4,5-di-
phenyloxazolidin-2-one (1abα) and (4S,5R,1ЈS)-3-[3-(Methylthio)-1-
(tributylstannyl)propyl]-4,5-diphenyloxazolidin-2-one (1abβ): Pre-
pared as described for 1aaα by alkylation of the sodium salt of
(4S,5R)-4,5-diphenyloxazolidin-2-one with the bromostannane 4a
(2.8 mmol). FC purification (petroleum ether/AcOEt 90:10) gave a
1:1 mixture of diastereomers 1abα and 1abβ as a viscous oil, yield
87%. Ϫ IR (α ϩ β, film): ν˜ ϭ 3060, 3020, 1735 cm–1. The two
diastereomers were separated by FC (petroleum ether/AcOEt ϭ
95:5).
˜
1cα: [α]D ϭ ϩ39.7 (c ϭ 1.35, CHCl3). Ϫ IR (α ϩ β, film): ν ϭ
1
3065, 3025, 1740 cm–1. – H NMR (CDCl3, 300 MHz): δ ϭ 0.84–
0.92 (m, 15 H), 1.18–1.31 (m, 9 H), 1.40–1.50 (m, 6 H), 2.58 (q,
J ϭ 7.3 Hz, 1 H), 4.05 (apparent t, JAB ϭ 8.1 Hz, 1 H), 4.57 (t,
J ϭ 8.8 Hz, 1 H), 4.93 (apparent t, JAB ϭ 8.1 Hz, 1 H), 7.26–7.44
(m, 5 H). – 13C NMR (CDCl3, 75 MHz): δ ϭ 10.7 (CH2, Bu3Sn),
13.8 (CH3, Bu3Sn), 15.9 (CH3), 27.5 (CH2, Bu3Sn), 29.2 (CH2,
Bu3Sn), 35.2 (CH), 59.8 (CH), 69.4 (CH2), 127.2 (CH), 129.0 (CH),
129.2 (CH), 138.1 (C), 158.9 (C). – C23H39NO2Sn (480.27): calcd.
C 5.52 H 8.18; found C 57.54, H 8.38.
1abα: [α]D ϭ ϩ18.3 (c ϭ 1.2, CHCl3). – 1H NMR (CDCl3,
200 MHz): δ ϭ 0.75 –1.00 (m, 15 H), 1.20–1.60 (m, 12 H), 1.95–
2.10 (m, 2 H), 2.10 (s, 3 H), 2.45–2.60 (m, 2 H), 2.79 (t, J ϭ
6.25 Hz, 1 H), 5.22 (d, J ϭ 8.6 Hz, 1 H), 5.81 (d, J ϭ 8.6 Hz, 1 H),
6.81–7.12 (m, 10 H). – 13C NMR (CDCl3, 50 MHz): δ ϭ 11.3
(CH2, Bu3Sn), 13.7 (CH3, Bu3Sn), 15.6 (CH3), 27.5 (CH2, Bu3Sn),
29.1 (CH2, Bu3Sn), 31.3 (CH2), 32.8 (CH2), 41.1 (CH2), 66.3 (CH),
78.8 (CH), 125.9 (CH), 127.7 (CH), 127.8 (CH), 128.2 (CH, ϫ2),
128.3 (CH), 134.1 (C), 135.1 (C), 159.2 (C).
1cβ: Eluting first – [α]D ϭ ϩ24 (c ϭ 1.9, CHCl3). – 1H NMR
(CDCl3, 300 MHz): δ ϭ 0.84–0.94 (m, 15 H) 1.16 (d, J ϭ 7.4 Hz,
3 H), 1.26–1.55 (m, 12 H), 2.78 (m, 1 H), 4.14 (dd, J ϭ 5.9 Hz,
J ϭ 7.35 Hz, 1 H), 4.51–4.62 (m, 2 H), 7.31–7.47 (m, 5 H). – 13C
1
1abβ: Eluting first. – [α]D ϭ ϩ18.3 (c ϭ 1.2, CHCl3). – H NMR
(CDCl3, 200 MHz): δ ϭ 0.80–1.00 (m, 15 H), 1.15–1.60 (m, 12 H), NMR (CDCl3, 75 MHz): δ ϭ 10.2 (CH2, Bu3Sn), 13.7 (CH3,
1.75 (s, 3 H), 1.90–2.25 (m, 4 H), 3.1 (dd, J ϭ 6.8, 7.6 Hz, 1 H), Bu3Sn), 18.8 (CH3), 27.5 (CH2, Bu3Sn), 29.2 (CH2, Bu3Sn), 39.2
1302
Eur. J. Org. Chem. 2000, 1297Ϫ1305

Synthesis of Highly Enantio-Enriched α-Amino Acids
(CH), 63.6 (CH), 69.7 (CH2), 127.6 (CH), 129.1 (CH), 129.2 (CH), phenyloxazolidin-2-one (1fβ): Prepared as described for 1aa by al-
FULL PAPER
139.3 (C), 158.5 (C).
kylation of the sodium salt of (S)-4-phenyloxazolidin-2-one with
the bromostannane 4f (2 mmol). FC purification (petroleum ether/
AcOEt 90:10) gave a 1:1 mixture of diastereomers 1fα and 1fβ,
yield 5%. The two diastereomers were separated by FC (petroleum
ether/AcOEt 95:5).
(4S,1ЈR)-3-[3-(Benzylthio)-1-(tributylstannyl)propyl]-4-phenyloxa-
zolidin-2-one (1dα) and (4S,1ЈS)-3-[3-(Benzylthio)-1-(tributylstan-
nyl)propyl]-4-phenyloxazolidin-2-one (1dβ): Prepared as described
for 1aa by alkylation of the sodium salt of (S)-4-phenyloxazolidin-
2-one with the bromostannane 4d (2.6 mmol). FC purification (pe-
troleum ether/AcOEt 90:10) gave a 1:1 mixture of diastereomers
4dα and 4dβ, yield 90%. The two diastereomers were separated by
FC (petroleum ether/AcOEt 95:5).
1fα: [α]D ϭ ϩ10.5 (c ϭ 1.2, CHCl3). – IR (α ϩ β, film): ν˜ ϭ 3070,
3030, 1740 cm–1. – 1H NMR (CDCl3, 300 MHz): δ ϭ 0.82–0.88
(m, 18 H), 0.92 (d, J ϭ 6.6 Hz, 3 H), 1.19–1.44 (m, 12 H), 2.20–
2.35 (m, 1 H), 2.43 (d, J ϭ 7.4 Hz, 1 H), 4.15 (dd, J ϭ 7.7 Hz, J ϭ
8.8 Hz, 1 H), 4.62 (apparent t, J ϭ 8.8 Hz, 1 H), 4.88 (dd, J ϭ
7.7 Hz, J ϭ 8.8 Hz, 1 H), 7.26–7.42 (m, 5 H). Ϫ 13C NMR (CDCl3,
75 MHz): δ ϭ 11.7 (CH2, Bu3Sn), 13.7 (CH3, Bu3Sn), 21.6 (CH3),
21.8 (CH3), 27.5 (CH2, Bu3Sn), 29.1 (CH2, Bu3Sn), 31.05 (CH),
49.4 (CH), 62.7 (CH), 69.4 (CH2), 127.7 (CH), 129.1 (CH), 129.2
(CH), 137.9 (C), 158.9 (C).
1dα: [α]D ϭ ϩ25.5 (c ϭ 1.5, CHCl3) Ϫ IR (α ϩ β, film): ν˜ ϭ
3080, 3060, 3020, 1740, 1600, 760, 700 cm–1. Ϫ H NMR (CDCl3,
1
300 MHz): δ ϭ 0.78–0.92 (m, 15 H), 1.18Ϫ1.38 (m, 12 H) 1.83 (m,
1 H), 2.04 (m, 1 H), 2.37 (dd, J ϭ 6.6, 8.5 Hz, 2 H), 2.67 (dd, J ϭ
5.9, 7.4 Hz, 1 H), 3.70 (s, 2 H), 4.08 (dd, J ϭ 7.0 Hz, JAB ϭ 8.8 Hz,
1 H), 4.45 (t, J ϭ 8.8 Hz, 1 H), 4.62 (dd, J ϭ 6.6 Hz, JAB ϭ 8.8 Hz,
1 H), 7.20–7.40 (m, 10 H). – 13C NMR (CDCl3, 75 MHz): δ ϭ 10.9
(CH2, Bu3Sn), 13.8 (CH3, Bu3Sn), 27.5 (CH2, Bu3Sn), 29.0 (CH2,
Bu3Sn), 29.8 (CH2), 31.1 (CH2), 36.4 (CH), 40.1 (CH2), 61.5 (CH),
69.3 (CH2), 127.1 (CH), 128.6 (CH), 128.9 (CH), 129.1 (CH), 129.2
(CH), 138.1 (C), 138.3 (C), 158.6 (C). – C31H47NO2SSn (616.49):
calcd. C 60.40, H 7.68; found C 60.47, H 7.76.
1fβ: Eluting first – [α]D ϭ ϩ30.55 (c ϭ 1.2, CHCl3) – 1H NMR
(CDCl3, 300 MHz): δ ϭ 0.60 (d, J ϭ 6.6 Hz, 3 H), 0.73 (d, J ϭ
6.6 Hz, 3 H), 0.86–0.93 (m, 15 H), 1.23–1.57 (m, 12 H), 2.10–2.22
(m, 1 H), 2.44 (d, J ϭ 9.2 Hz, 1 H), 4.27 (apparent t, J ϭ 7.7 Hz,
1 H), 4.50 (dd, J ϭ 7.3, JAB ϭ 8.8 Hz, 1 H), 4.57 (dd, J ϭ 8.1 Hz,
JAB ϭ 8.8 Hz, 1 H) 7.34–7.42 (m, 5 H). – 13C NMR (CDCl3,
75 MHz): δ ϭ 11.2 (CH2, Bu3Sn), 13.7 (CH3, Bu3Sn), 21.6 (CH3),
21.8 (CH3), 27.6 (CH2, Bu3Sn), 29.2 (CH2, Bu3Sn), 30.4 (CH), 53.7
(CH), 63.9 (CH), 69.4 (CH2), 128.5 (CH), 129.0 (CH), 129.3 (CH),
138.0 (C), 159.0 (C).
1
1dβ: Eluting first. Ϫ [α]D ϭ ϩ27.2 (c ϭ 1.5, CHCl3). – H NMR
(CDCl3, 300 MHz): δ ϭ 0.82–0.93 (m, 15 H), 1.27–1.49 (m, 12 H),
1.80–2.09 (m, 4 H), 2.86 (t, J ϭ 6.7 Hz, 1 H), 3.35 (d, JAB
13.6 Hz, 1 H), 3.44 (d, JAB ϭ 13.6 Hz, 1 H), 4.2 (dd, J ϭ 5.9 Hz,
J ϭ 7.3 Hz, 1 H), 4.47–4.58 (m, 2 H), 7.15–7.39 (m, 10 H). – 13C
NMR (CDCl3, 75 MHz): δ ϭ 10.4 (CH2, Bu3Sn), 13.8 (CH3,
Bu3Sn), 27.5 ( CH2, Bu3Sn), 29.1 (CH2, Bu3Sn), 31.6 (CH2), 35.5
(CH2), 43.9 (CH), 63.4 (CH), 69.6 (CH2), 126.9 (CH), 128.0 (CH),
128.5 (CH), 128.9 (CH), 129.2 (CH), 129.4 (CH), 138.3 (C), 158.7
(C).
ϭ
(4S,1ЈR)-3-[Benzyloxy-1-(tributylstannyl)ethyl]-4-phenyloxazolidin-
2-one (1gα) and (4S,1ЈS)-3-[Benzyloxy-1-(tributylstannyl)ethyl]-4-
phenyloxazolidin-2-one (1gβ): Prepared as described for 1aa by al-
kylation of the sodium salt of the bromostannane 4g (1 mmol). FC
purification (petroleum ether/AcOEt 90:10) gave a 1:1 mixture of
diastereomers 1gα and 1gβ, yield 55%. An attempt to separate the
two diastereomers by FC was unsuccessful. Ϫ IR (α ϩ β, film):
ν˜ ϭ 3080, 3060, 3030, 1745, 1605, 1590, 1495 cm–1. – 13C NMR
(CDCl3, 75 MHz): δ ϭ 10.7–11.1 (CH2, Bu3Sn), 13.7–13.8 (CH3,
Bu3Sn), 27.5–27.8 (CH2, Bu3Sn), 29.08, 29.11 (CH2, Bu3Sn), 41.9,
45.2 (CH), 63.1, 63.2 (CH), 69.60, 70.0 (CH2) 70.4, 72.53 (CH2),
72.62, 73.1 (CH2), 127.50Ϫ129.14 (CH, Ar), 138.20, 138.46, 138.51,
138.95 (C) 158.85, 158.89 (C).
(4S,1ЈR)-4-Phenyl-3-[2-phenyl-1-(tributylstannyl)ethyl]oxazolidinon-
2-one (1eα) and (4S,1ЈS)-4-Phenyl-3-[2-phenyl-1-tributylstannylethyl]-
oxazolidinon-2-one (1eβ): Prepared as described for 1aa by al-
kylation of the sodium salt of (S)-4-phenyloxazolidin-2-one with
the bromostannane 4e (2.5 mmol). FC purification (petroleum
ether/AcOEt 90:10) gave a 1:1 mixture of diastereomers 1eα and
1eβ, yield 10%. An attempt to separate the two diastereomers by
FC (petroleum ether/AcOEt 95:5) was unsuccessful. Nevertheless
when the reaction of the 1:1 mixture was conducted with one
equivalent of nBuLi (THF, –70 °C), 1eα was found not to have
reacted and was recovered as such after work up and purification.
Transmetallation of the N-(α-Stannylalkyl)oxazolidinones 1a–d and
Carboxylation
(2S,4ЈS)-4-Methylthio-2-(2Ј-oxo-4Ј-phenyloxazolidin-3Ј-yl)butanoic
Acid (6aaα): To the 1:1 mixture of diastereomers 1aaα and 1aaβ
(0.92 g, 1.7 mmol) in THF (17 mL) was added dropwise nBuLi
(0.68 mL, 1.7 mmol, 2.5  solution in hexanes) at –78 °C. The yel-
low mixture was stirred for 5 min and CO2 was bubbled through
the solution. The mixture was poured into water (40 mL) and ex-
tracted with petroleum ether (2 ϫ 30 mL). The aqueous phase was
acidified to pH 1 with HCl 6  and extracted with CH2Cl2 (3 ϫ
50 mL). The combined organic phases were dried over Na2SO4 and
evaporated under reduced pressure to afford 6aaα as a viscous oil
(0.427 g, 85%). – Note 1: the yield could be increased by using a
slight excess of nBuLi (ca 90% with 1.2 equiv.) but it was not appli-
cable to our procedure due to probable loss of radioactivity by
formation of 1-[11C] pentanoic acid. – Note 2: the total time of the
process was drastically reduced to 15–20 min when small scale
(range: 35–150 µmol) manipulations using conical microvial glass-
ware were adopted. In this case, CO2 bubbling needed 30 sec to
1 min and the number of extractions were reduced to 1 or 2; yields:
1eα: IR (α ϩ β, film): ν˜ ϭ 3080, 3060, 3020, 1745, 1600, 1495, 700
cm–1. – 1H NMR (CDCl3, 300 MHz): δ ϭ 0.78–0.90 (m, 15 H),
1.18–1.45 (m, 12 H), 2.77 (dd, J ϭ 4.8 Hz, J ϭ 14.3 Hz, 1 H), 2.78
(dd, J ϭ 4.8 Hz, J ϭ 12.1 Hz, 1 H), 3.12 (dd, J ϭ 12.1 Hz, J ϭ
14.3 Hz, 1 H), 3.76 (dd, JAB ϭ 7.3 Hz, J ϭ 8.8 Hz, 1 H), 3.96 (dd,
JAB ϭ 5.3 Hz, JAB ϭ 8.5 Hz, 1 H), 4.31 (apparent t, J ϭ 8.8 Hz, 1
H), 6.96–7.35 (m, 10 H). – 13C NMR (CDCl3, 75 MHz): δ ϭ 10.5
(CH2, Bu3Sn), 13.8 (CH3, Bu3Sn), 27.5 (CH2, Bu3,Sn), 29.0 (CH2,
Bu3Sn), 38.3 (CH2), 43.2 (CH), 62.3 (CH), 69.3 (CH2), 126.6 (CH),
127.5 (CH), 128.7 (CH), 128.96 (CH), 129.02 (CH), 138.0 (C),
141.6 (C)158.4 (C).
1eβ: 13C NMR (CDCl3, 50 MHz, selected data deduced from a
spectra of an α/β mixture): δ ϭ 38.3 (CH2, C2Ј), 46.1 (CH, C1Ј),
63.6 (CH, C4) 69.7 (CH2, C5), 158.4 (C, C2).
(4S,1RЈ)-3-[2-Methyl-1-(tributylstannyl)propyl]-4-phenyloxazolidin-
2-one (1fα) and (4S,1SЈ)-3-[2-Methyl-1-(tributylstannyl)propyl]-4- 60 to 85%.
Eur. J. Org. Chem. 2000, 1297Ϫ1305
1303

F. Jeanjean, G. Fournet, D. Le Bars, J. Gore
FULL PAPER
6aaα: [α]D ϭ ϩ16.4 (c ϭ 1.05, CHCl3). – IR (film): ν˜ ϭ 3500, 3100, stirred for 2 h at 60° C then overnight at room temp. The mixture
3030, 1760, 1480, 1460, 1410 cm–1. – 1H NMR (CDCl3, 200 MHz): was evaporated under reduced pressure, dissolved with water
δ ϭ 1.95 (s, 3 H) 2.05 (m, 2 H), 2.41 (t, J ϭ 7.5 Hz, 2 H), 4.27 (dd,
J ϭ 6.9 Hz, J ϭ 8.6 Hz, 1 H), 4.44 (dd, J ϭ 5.2 Hz, J ϭ 9.4 Hz, 1
(50 mL) and extracted with CH2Cl2 (4 ϫ 50 mL). The combined
organic phases were dried over Na2SO4 and the solvent was re-
H), 4.72 (apparent t, J ϭ 8.8 Hz, 1 H), 5.00 (dd, J ϭ 6.9 Hz, J ϭ moved by rotary evaporation. The crude product was then briefly
8.9 Hz, 1 H), 7.40 (m, 5 H), 9.30 (broad s, 1 H). – 13C NMR
purified on silica gel (petroleum ether/AcOEt, 60:40) to give a dia-
(CDCl3, 50 MHz): 15.0 (CH3), 28.4 (CH2), 30.6 (CH2), 55.3 (CH), stereomeric mixture of amino alcohols (1.7 g, 6.8 mmol) which was
60.1 (CH), 71.0 (CH2), 127.7 (CH), 129.3 (CH), 129.4 (CH), 138.4
(C), 158.9 (C), 174.8 (C). – EI MS; m/z (%): 221 (20), 203 (18), 104
redissolved in CH2Cl2 (9 mL) and pyridine (1.15 mL, 14.2 mmol).
A solution of triphosgene (0.706 g, 2.38 mmol) in CH2Cl2 (8 mL)
(100), 103 (28), 91 (32), 77 (21) 61 (43), 51 (12), 45 (20). – CI was then added dropwise at 0 °C and stirred for 3 h. After one
HRMS: calcd. for C14H18NO4S (MHϩ): 296.0956; found 296.0956.
night the mixture was diluted with diethyl ether (200 mL), washed
with HCl (0.6 , 30 mL) and brine (20 mL). The organic phase was
dried over Na2SO4 and the solvent was removed. The 1H NMR
spectrum showed the crude product to be an 80:20 diastereomeric
ratio of 7α/7β. After FC purification and collection of the pure
fractions (petroleum ether/AcOEt, 70:30 then 60:40) pure 7α
(1.56 g, 83%; 55% from phenylglycinol) and 7β (0.11 g, 6%; 4%
from phenylglycinol) were obtained.
(2S,4ЈS,5ЈR)-4-(Methylthio)-2-(2Ј-oxo-4Ј,5Ј-diphenyloxazolidin-3Ј-
yl)butanoic Acid (6ab): Prepared as described for 6aaα starting from
1ab (1:1 mixture of diastereomers α and β, 2 mmol). Viscous oil,
yield 78%. Ϫ [α]D ϭ ϩ22.6 (c ϭ 1.05, CHCl3). – 1H NMR (CDCl3,
200 MHz): δ ϭ 1.84 (s, 3 H), 2.05 (m, 2 H), 2.38 (t, J ϭ 7.5 Hz, 2
H), 4.65 (dd, J ϭ 5.7 Hz, J ϭ 8.9 Hz, 1 H), 5.25 (d, J ϭ 8.3 Hz, 1
H), 6.10 (d, J ϭ 8.3 Hz, 1 H), 7.05 (m, 10 H), 10.10 (broad s, 1
H). – 13C NMR (CDCl3, 50 MHz): δ ϭ 14.7 (CH3), 28.9 (CH2)
30.7 (CH2), 57.0 (CH), 63.9 (CH) 81.3 (CH), 126.0 (CH), 127.8
(CH), 128.0 (CH), 128.2 (CH), 134.2 (C), 135.8 (C), 159.7 (C),
175.6 (C). – EI MS; m/z (%): 180 (42), 179 (34), 165 (22), 105 (33),
91 (43), 77 (53), 61 (34), 51 (71), 50 (40), 47 (62), 45 (73), 44 (100).
7α: white solid, m.p. 74 °C. – [α]D ϭ ϩ96 (c ϭ 1, CHCl3). Ϫ IR
(KBr): ν˜ ϭ 3060, 3005, 2240, 1765, 780, 760, 700 cm–1. Ϫ 1H NMR
(CDCl3, 200 MHz): δ ϭ 1.98 (s, 3 H), 2.10–2.45 (m, 2 H),
2.47Ϫ2.60 (m, 2 H), 4.26 (dd, J ϭ 7.8 Hz, J ϭ 8.6 Hz, 1 H), 4.59
(dd, J ϭ 7.7 Hz, J ϭ 7.9 Hz, 1 H), 4.79 (apparent t, J ϭ 8.7 Hz, 1
H), 4.86 (dd, J ϭ 7.9 Hz, J ϭ 8.5 Hz, 1 H), 7.35Ϫ7.50 (m, 5 H).
Ϫ EI MS; m/z (%): 276 (12), 217 (13), 171.(8), 158 (5), 130 (5), 116
(6), 104 (100), 91 (17), 77 (18), 61 (21), 51 (16), 47 (15). –
C14H16N2O2S (276.36): calcd. C 60.85, H 5.84; found C 60.68, H
5.65.
(2S,4ЈS)-4-Methyl-2-(2Ј-oxo-4Ј-phenyloxazolidin-3Ј-yl]pentanoic
Acid (6b): Prepared as described for 6aaα from 1b (0.8 mmol). Vis-
cous oil, yield 85%. Ϫ [α]D ϭ ϩ49.5 (c ϭ 0.5, CHCl3). – 1H MNR
(CDCl3, 300 MHz): δ ϭ 0.49 (d, J ϭ 6.2 Hz, 3 H), 0.85 (d, J ϭ
6.2 Hz, 3 H), 1.21–1.48 (m, 3 H), 4.25 (dd, J ϭ 6.6 Hz, J ϭ 8.8 Hz,
1 H), 4.48 (dd, J ϭ 4.0 Hz, J ϭ 10.3 Hz, 1 H), 4.71 (apparent t,
J ϭ 8.8 Hz, 1 H), 5.04 (dd, J ϭ 6.6 Hz, J ϭ 8.8 Hz, 1 H), 7.39 (m,
5 H), 10.18 (broad s, 1 H). – 13C NMR (CDCl3, 75 MHz): δ ϭ
21.1 (CH3), 22.5 (CH3), 24.4 (CH), 37.9 (CH2), 55.6 (CH), 59.4
(CH), 71.1 (CH2), 127.6 (CH), 129.18 (CH), 129.19 (CH), 139.3
(C), 159.6 (C), 175.3 (C).
7β: Eluting first, viscous oil. – [α]D ϭ ϩ58 (c ϭ 1, CHCl3). –IR
(film): ν˜ ϭ 3060, 3015, 2220, 1750, 1605, 1590, 790, 765, 700
1
cm–1. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 1.53–1.72 (m, 2 H), 1.97
(m, 3 H), 2.35–2.50 (m, 2 H), 4.32 (dd, J ϭ 7.3, 8.9 Hz, 1 H), 4.73
(apparent t, J ϭ 8.9 Hz, 1 H), 4.98 (dd, J ϭ 7.3 Hz, J ϭ 8.5 Hz, 1
H), 7.49 (m, 5 H). – EI MS; m/z (%): 276 (7), 130 (5), 116 (7), 105
(8), 104 (100) 91 (22), 77 (20), 61 (22), 51 (22), 45 (19). –
C14H16N2O2S (276.36): calcd. C 60.85, H 5.84; found C 60.56, H
5.90.
(2S,4ЈS)-4-Methyl-2-(2Ј-oxo-4Ј-phenyloxazolidin-3Ј-yl)propanoic
Acid (6c): Prepared as described for 6aaα starting from 1c
(1 mmol). Viscous oil, yield 72%. Ϫ [α] ϭ ϩ98 (c ϭ 0.6, MeOH). –
1H NMR (CD3OD, 300 MHz): δ ϭ 1.10 (d, J ϭ 7.4 Hz, 6 H), 4.09
(dd, J ϭ 6.6 Hz, J ϭ 8.5 Hz, 1 H), 4.32 (q, J ϭ 7.4 Hz, 1 H), 4.70
(apparent t, J ϭ 8.8 Hz, 1 H), 5.10 (dd, J ϭ 6.6 Hz, J ϭ 8.8 Hz, 1
H), 7.28–7.44 (m, 5 H). – 13C NMR (CD3OD, 75 MHz): δ ϭ 18.5
(CH3) 56.2 (CH), 63.0 (C), 75.0 (CH2), 130.8 (CH), 132.5 (CH),
132.8 (CH), 143.9 (C), 163.6 (C), 176.7 (C).
(2R,4ЈS)-4-Methylthio-2-[(2Ј-oxo-4Ј-phenyloxazolidin-3Ј-yl]butanoic
Acid (6aaβ): The nitrile 7β (1.56 g, 5.64 mmol) finely suspended in
HCl (12 , 16 mL) was stirred for 5 h at 55° C. The mixture was
cooled to room temp. and poured into water (40 mL) and CH2Cl2
(100 mL). The aqueous phase was extracted with CH2Cl2 (2 ϫ
100 mL) and the combined organic phases were dried over Na2SO4.
The solvent was removed under reduced pressure to give 1.5 g
(yield 90%) of a viscous oil. 1H NMR spectroscopy showed this
crude product to be a 10:90 diastereomeric mixture of 6aaα/6aaβ.
(2S,4ЈS)-4-(Benzylthio)-2-(2Ј-oxo-4Ј-phenyloxazolidin-3Ј-yl)butanoic
Acid (6d): Prepared as described for 6aaα starting from 1d
(1 mmol). Viscous oil, yield 80%. Ϫ [α] ϭ ϩ14 (c ϭ 3.1, CHCl3). –
1H NMR (CDCl3, 300 MHz): δ ϭ 1.75 Ϫ 2.12 (m, 2 H), 2.32 (m,
2 H), 3.58 (broad s, 2 H), 4.19 (dd, J ϭ 6.98 Hz, J ϭ 8.83 Hz, 1
H), 4.34 (dd, J ϭ 5.15 Hz, J ϭ 9.56 Hz, 1 H), 4.60 (t, J ϭ 8.83 Hz,
1 H), 4.84 (dd, J ϭ 6.98 Hz, J ϭ 8.82 Hz, 1 H), 7.18 Ϫ 7.40 (m,
10 H), 9.0 (broad s, 1 H). – 13C NMR (CDCl3, 75 MHz): δ ϭ 27.9
(CH2), 28.6 (CH2), 35.9 (CH2), 55.4 (CH), 60.1 (CH), 71.0 (CH2),
127.1 (CH), 127.7 (CH), 128.6 (CH), 128.9 (CH), 129.26 (CH),
129.32 (CH), 138.1 (C), 138.3 (C), 158.9 (C), 174.9 (C).
6aaβ: 1H NMR (CDCl3, 200 MHz): δ ϭ 1.92 (s, 3 H), 2.20–2.42
(m, 2 H), 2.50–2.65 (m, 2 H), 3.84 (dd, J ϭ 4.9 Hz, J ϭ 9.0 Hz, ),
4.24 (apparent t, J ϭ 9.0 Hz, 1 H), 4.69 (apparent t, J ϭ 8.7 Hz, 1
H), 4.94 (apparent t, J ϭ 9.0 Hz, 1 H), 7.42 (m, 5 H). – 13C NMR
(CDCl3, 50 MHz): δ ϭ 14.7 (CH3), 27.6 (CH2), 30.8 (CH2), 54.8
(CH), 62.5 (CH), 70.2 (CH2), 127.3 (CH), 128.1 (CH), 129.6 (CH),
136.1 (C), 158.8 (C), 174.9 (C).
Preparation of Amino Acids
Preparation of 6aaβ. – (2R,4ЈS)-4-Methylthio-2-(2Ј-oxo-4Ј-phenyl-
oxazolidin-3Ј-yl)butanenitrile (7α) and (2R,4ЈS)-4-Methylthio-2-(2Ј-
L-Methionine: To a solution of lithium (0.048 g, 6.8 mmol) dis-
oxo-4Ј-phenyloxazolidin-3Ј-yl)butanenitrile (7β): To a mixture of solved in ammonia (ca. 30 mL) were added compound 6aaα
(S)-4-phenylglycinol (1.4 g, 10.2 mmol) and potassium cyanide
(0.25 g, 0.85 mmol) in THF (5 mL) and tBuOH (0.65 mL) at –70°
(0.548 g, 11.2 mmol) in CH2Cl2 (10 mL) was added 3-methylthio-
C. After 5 min, the deep blue mixture was decolourised by adding
propanal (1.02 mL, 10.2 mmol). Acetic acid (0.93 mL, 16.25 mmol) NH4Cl (0.5 g) and the solvents were quickly removed under re-
was added dropwise at room temp. and the resulting solution was
1304
duced pressure with gentle warming. The white residue was taken
Eur. J. Org. Chem. 2000, 1297Ϫ1305

Synthesis of Highly Enantio-Enriched α-Amino Acids
FULL PAPER
For a review on the Strecker synthesis, see ref. [1a] pp 208–229.
[2]
up in water (30 mL), acidified to pH 1 and extracted with Et2O (2
ϫ 10 mL). NaOH was added until pH 9 was reached and the solu-
tion was filtered through a DOWEX 50Wϫ8 (Hϩ form, 28–35
mesh, 20 g) ion exchange column. An elution with water (100 mL,
pH acid to neutral), was followed by aqueous 2% NH4OH. Positive
ninhydrin fractions were collected and evaporated, yielding pure
methionine (0.107 g, 85%). The structure was confirmed by com-
parison of 1H NMR spectroscopic data (DCl 1  or NaOD 1 )
with authentic samples. CSP-HPLC analysed on a Chirobiotic T
(Astec ) column [4.6 ϫ 250 mm, 5µm, eluent: EtOH/H2O 60:40 at
1 mL. min–1, det. UV 200 nm] showed only one peak (ee 95%) at
tR ϭ 5.19 min (-isomer: tR ϭ 8.06 min).
[3] [3a]
M. S. Patel, M. Worsley, Can. J. Chem. 1970, 48,
1881Ϫ1884. For more recent examples on asymmetric Strecker
[3b]
synthesis see:
G. Dyker, Angew. Chem. Int. Ed. Engl. 1997,
[3c]
36, 1700–1702. Ϫ
D. Ma, H. Tian, G. Zou, J. Org. Chem.
1999, 64, 120Ϫ125 and references cited therein.
P. Beak, S. T. Kerrick, J. Am. Chem. Soc. 1991, 113,
9708Ϫ9710.
[4]
[5] [5a]
M. Schlosser, D. Limat, J. Am. Chem. Soc. 1995, 117,
12342Ϫ12343. Ϫ [5b] N. Voyer, J. Roby, Tetrahedron Lett. 1995,
36, 6627Ϫ6630.
[6]
L. Duhamel, P. Duhamel, S. Fouqay, J. J. Eddine, O. Peschard,
J. C. Plaquevent, A. Ravard, R. Solliard, J. Y. Valnot, H.
Vicens, Tetrahedron 1988, 44, 5495Ϫ5506.
[7]
[8]
[9]
´
´
F. Jeanjean, N. Perol, J. Gore, G. Fournet, Tetrahedron Lett.
1997, 38, 7547Ϫ7550.
L-Leucine: Prepared as described for -methionine starting from
D. Comar, PET for Drug Development and Evaluation, Kluwer
Academic Publishers, Dodrecht, 1995.
P. Bobillier, E. Grange, A. Gharib, M. Leclerc, N. Sarda, P.
Lepetit, in PET Studies on Amino Acid Metabolism and Protein
Synthesis, Kluwer Academic Publishers, Dodrecht, 1993, 41–
52.
compound 6b (0.88 mmol), yield 74%. The structure was confirmed
1
by comparison of H NMR spectroscopic data (DCl, 1 ) with an
authentic sample. ee 95% determined by 19F NMR spectroscopic
analysis of the Mosher amide derivative,[18] only one peak was de-
tected at δ ϭ –69.30 [-isomer δ ϭ –69.6].
[10]
[11]
J. M. Bolste, W. Vaalburg, Ph. H. Elsinga, H. Wynberg, M. G.
Woldring, Appl. Radiat. Isot. 1986, 37, 1069Ϫ1070.
L-Alanine: Prepared as described for -methionine starting from
[11a]
For α-nitrogen lithiation with (R)-Li-Sparteine see:
Y. S.
compound 6c (0.76 mmol), yield 84%. The structure was confirmed
Park, M. L. Boys, P. Beak, J. Am. Chem. Soc. 1996, 118,
1
[11b]
by comparison of H NMR spectroscopic data (DCl 1 ) with an
3757Ϫ3758. Ϫ
P. Beak, A. Basu, D. J. Gallagher, Y. S.
authentic sample. ee 95% determined by 19F NMR spectroscopic
analysis of the Mosher amide derivative.[18] A 98:2 ratio in favour
of the -isomer (δ ϭ –69.28) was found (-isomer δ ϭ –69.68).
Park, S. Thayumanavan, Acc. Chem. Res. 1996, 29,
552Ϫ560.[11c] Y. S. Park, P. Beak, J. Org. Chem. 1997, 62,
1574Ϫ1575. Ϫ [11d] D. Hoppe, T. Hense, Angew. Chem. Int. Ed.
Engl. 1997, 36, 2282–2316 and references cited therein.
[12] [12a]
W. H. Pearson, A. C. Lindbeck, J. Am. Chem. Soc. 1991,
[12b]
L-Homocysteine: Prepared as described for -methionine starting
113, 8546Ϫ8548. Ϫ
W. H. Pearson, A. C. Lindbeck, J. W.
from compound 6d (0.45 mmol), yield 74%. The structure was con-
firmed by comparison of 1H NMR spectroscopic data (DCl 1 )
with an authentic sample. ee ϭ 92% established by 19F NMR spec-
troscopic analysis of the Mosher amide derivative.[18] A 96:4 ratio
in favour of the -isomer was found. [δ ϭ –69.26, –69.34 and –
69.72 (S-acyl)]; -isomer [δ ϭ –69.56, –69.60 and –69.69 (S-acyl)].
Because of degradation on the analytical support, CSP-HPLC ana-
lysis was not suitable in this case.
Kampf, J. Am. Chem. Soc. 1993, 115, 2622Ϫ2636.
For reviews on oxazolidinones as chiral auxilliaries, see: [13a] D.
Ager, I. Prakash, D. R. Schaad, Chem. Rev. 1996, 835–875. Ϫ
[13b] D. Ager, I. Prakash, D. R. Schaad, Aldrichimica Acta 1997,
30, 3–11.
[13]
[14] [14a]
S. Ram, L. D. Spicer, Synthetic Commun. 1987, 17, 415–
418. Ϫ [14b] W. H. Pearson, A. C. Lindbeck, J. Org. Chem. 1989,
54, 5651–5654.
[15] [15a]
D. A. Evans, E. B. Sjogren, Tetrahedron Lett. 1985, 26,
[15b]
3783Ϫ3786. Ϫ
I. Ojima, H. J. C. Chen, X. Qiu, Tetrahed-
ron 1988, 44, 5307Ϫ5318. Ϫ [15c] See also: S. Sabelle, D. Lucet,
T. Le Gall, C Mioskowski, Tetrahedron Lett. 1998, 39,
2111Ϫ2114.
Acknowledgments
[16] [16a]
[16b]
F. Jeanjean, PhD thesis, Univ. Lyon, 1999. Ϫ
F. Jean-
´
ˆ
Thanks are due to Region Rhone-Alpes for financial support and
for a scholarship to F. J. Scientific discussions with Dr D. Comar
(CERMEP-Lyon) were greatly appreciated.
´
jean, G. Fournet, D. Lebars, N. Roidot, L. Vichot, J. Gore, D.
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