Samarium iodobinaphtholate: An efficient catalyst for enantioselective aza-michael additions of O-benzylhydroxylamine to N-alkenoyloxazolidinones

Article abstract of DOI:10.1002/ejoc.201100041

Samarium diiodide is an efficient catalyst for the aza-Michael addition of O-benzylhydroxylamine to α,β-unsaturated N-acyloxazolidinones leading to mixtures of the Michael adduct and the product resulting from its amidation. Samarium iodobinaphtholate cat

Full text of DOI:10.1002/ejoc.201100041

FULL PAPER
DOI: 10.1002/ejoc.201100041
Samarium Iodobinaphtholate: An Efficient Catalyst for Enantioselective Aza-
Michael Additions of O-Benzylhydroxylamine to N-Alkenoyloxazolidinones
Dorian Didier,[a] Abdelkrim Meddour,[b] Sophie Bezzenine-Lafollée,*[a] and
Jacqueline Collin*[a,c]
Keywords: Asymmetric catalysis / Aza-Michael reactions / Lanthanides / Samarium / Nonlinear effect
Samarium diiodide is an efficient catalyst for the aza-Michael
addition of O-benzylhydroxylamine to α,β-unsaturated N-
acyloxazolidinones leading to mixtures of the Michael ad-
duct and the product resulting from its amidation. Samarium
iodobinaphtholate catalyzed reactions selectively afford the
Michael adducts with enantiomeric excesses up to 88%. An
isoinversion effect with temperature is observed with the
highest enantiomeric excess at –40 °C.
dition of O-alkylhydroxylamines to conjugated enones with
high enantioselectivity, whereas moderate to high enantio-
meric excesses are achieved by organocatalysts.[9] The 1,4-
addition of O-alkylhydroxylamines to α,β-unsaturated es-
ters or its analogs has been less investigated. Copper triflate
coordinated with pybox catalyzes the formation of β-hy-
droxylamino derivatives from alkylidene malonate with en-
antiomeric excesses of up to 76%.[10] Sibi studied the influ-
ence of templates on the enantioselectivity of the magne-
sium bis(oxazoline)-catalyzed or the organocatalyzed con-
jugate addition of hydroxylamine ethers.[11] High enantio-
meric excesses have been obtained by Shibasaki for the ad-
dition of methoxylamine to α,β-unsaturated N-acylpyrroles
catalyzed by heterobimetallic complexes.[12] The first cata-
lysts, titanium taddolate and binaphtholate, used for the ad-
dition of hydroxylamine ethers to α,β-unsaturated N-acyl-
oxazolidinones gave low enantiomeric excesses.[13] Reac-
tions catalyzed by scandium triflate associated to pybox li-
gands afforded mixtures of the aza-Michael adduct and its
amidation product with good enantioselectivities.[14] We
have previously investigated the use of samarium diiodide
as an efficient Lewis acid catalyst for a wide range of C–C
and C–N bond formations and found that samarium iodo-
binaphtholate is an efficient catalyst for some of these reac-
tions.[15] Recently, we described the use of both samarium
iodides for the aza-Michael addition of aromatic amines to
α,β-unsaturated alkenoyl oxazolidinones.[16] Good enantio-
meric excesses were obtained for some samarium iodo-
binaphtholate catalyzed reactions. We have now extended
this study to the conjugate addition of O-benzylhydroxyl-
amine.
Introduction
In recent years the asymmetric addition of amines or ni-
trogen derivatives to an activated or nonactivated double
bond has attracted intense interest as an efficient atom-eco-
nomical method for the formation of C–N bonds. A variety
of enantioselective catalysts which are the focus of several
reviews have been described for hydroamination reactions
as well as for aza-Michael additions to conjugated double
bonds.[1,2] Inter- and intramolecular enantioselective aza-
Michael reactions are now widely used for the synthesis of
various nitrogen heterocycles and pharmaceutically inter-
esting molecules.[3] Catalytic asymmetric additions of dif-
ferent nitrogen nucleophiles, such as amines, carbamates,
azides, or nitrogen heterocycles, to α,β-unsaturated ester
precursors are efficient methods for the synthesis of natural
and unnatural α,β-amino acid derivatives.[4,5] High enantio-
meric excesses have been obtained for the addition of
amines to chelating substrates, such as alkenoyl-oxazolidin-
ones or carbamates, by chiral catalysts based on nickel and
bis(oxazoline) ligands or palladium and chiral phos-
phanes.[6]
Amongst the different nitrogen nucleophiles employed
for aza-Michael reactions, O-alkylhydroxylamines are espe-
cially attractive since adducts can easily be transformed into
valuable compounds such as aziridines[7] or isoxazolines.[8]
Chiral heterobimetallic complexes can catalyze the 1,4-ad-
[a] Equipe de Catalyse Moléculaire, Université Paris-sud,
ICMMO, UMR 8182,
91405 Orsay, France
Fax: +33-1-69154680
E-mail: Sophie.Bezzenine@u-psud.fr
[b] Equipe de RMN en Milieu Orienté, Université Paris-sud,
ICMMO, UMR 8182,
91405 Orsay, France
Results and Discussion
[c] Centre National de la Recherche Scientifique (CNRS),
91405 Orsay, France
We first studied the catalytic activity of samarium di-
iodide (10 mol-%) in the addition of O-benzylhydroxyl-
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100041.
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A Catalyst for an Enantioselective Aza-Michael Addition
Scheme 1. Samarium diiodide catalyzed additions of O-benzylhydroxylamine (2) to α,β-unsaturated N-acyloxazolidinones.
amine (1.2 equiv.) to various unsaturated N-acyloxazolid- was observed, but interestingly we found that samarium di-
inones in dichloromethane at room temperature (Scheme 1). iodide was the most efficient catalyst for this transforma-
Total conversion was observed for all α,β-unsaturated N- tion.
acyloxazolidinones substituted on the terminal carbon of
the double bond (Table 1). Substrates 1b and 1c containing
a propyl or an isopropyl group exclusively furnished
Michael adducts 3b and 3c, respectively. The reaction of 1a
(R1 = Me), 1d (R1 = CO2Et), and 1e (R1 = Ph) afforded a
mixture of two products, Michael adducts 3a, 3d, and 3e,
and 4a, 4d, and 4e arising from the amidation reaction of
rated N-acyloxazolidinone 1b catalyzed by various Lewis acids.
the corresponding compounds with O-benzylhydroxyl-
Scheme 2. Addition of O-benzylhydroxylamine (2) to α,β-unsatu-
amine. The Michael adducts were the major products ob-
tained (Table 1, Entries 1, 4, and 5). Substrate 1f, substi-
tuted on the internal carbon of the double bond, afforded
after prolonged reaction times the unsaturated derivative re-
sulting from the amidation with O-benzylhydroxylamine.
Table 2. Addition of 2 to 1b catalyzed by various Lewis acids.
Entry
Catalyst
% Conversion[a]
1
2
3
4
Cu(OTf)2
Sc(OTf)3
Yb(OTf)3
SmI2
12
64
90
100
Table 1. Addition of O-benzylhydroxylamine (2) to various α,β-un-
saturated N-acyloxazolidinones catalyzed by samarium diiodide.
1
[a] Conversion was measured by H NMR.
Entry
Substrate
Time
3/4[a]
% yield 3[b]
The catalytic activity and enantioselectivity of samarium
iodobinaphtholate for aza-Michael additions of O-benzyl-
hydroxylamine to α,β-unsaturated N-acyloxazolidinones
were then investigated. We first studied the reaction with
oxazolidinone 1a. O-Benzylhydroxylamine (1.2 equiv.) was
added at room temperature to 10 mol-% of samarium iodo-
binaphtholate 5 in dichloromethane in the presence of mo-
lecular sieves (Scheme 3). Since the enantioselectivities of
the samarium iodobinaphtholate catalyzed reactions are
dramatically influenced by temperature, the aza-Michael
1
2
3
4
5
6
1a (R1 = Me, R2 = H)
1b (R1 = nPr, R2 = H)
1c (R1 = iPr, R2 = H)
1d (R1 = CO2Et, R2 = H)
1e (R1 = Ph, R2 = H)
1f (R1 = H, R2 = CH3)
10 min
10 min
12 h
24 h
24 h
70:30
100:0
100:0
74:26
71:29
0:0[d]
58
62[c]
59[c]
29[c]
60
48 h
0
[a] Ratio determined by NMR of the crude product. [b] Isolated
yield, 100% conversion. [c] Low yield is due to purification diffi-
culties. [d] The unsaturated product resulting from trans amidation
was obtained as the sole product in 60% yield.
When substrates were substituted with a methyl (1a) or addition of O-benzylhydroxylamine was performed at vari-
a linear alkyl group (1b), addition of O-benzylhydroxyl- ous temperatures (Table 3). Total conversions were obtained
amine to oxazolidinones was completed in only 10 min at in almost all cases. At room temperature, the same ratio
room temperature (Entries 1 and 2). Slower reactions were of 3a/4a to that given by samarium diiodide was observed.
observed with substrates containing a more bulky alkyl However, at lower temperatures the enantioselective aza-
group (Entry 3, R1 = iPr) or an electron-withdrawing group Michael addition of O-benzylhydroxylamine exclusively af-
such as an ester or a phenyl group (Entries 4 and 5). The forded Michael adduct 3a. Our catalytic system is thus
activity of samarium diiodide in aza-Michael reactions was more selective than the Fukasawa catalyst based on scan-
compared to that of copper(II), scandium(III), and ytter- dium triflate.[14] Moreover, we found that the variation in
bium(III) triflate which are known to be very efficient Lewis the enantiomeric excess was not monotonic with tempera-
acid catalysts (Scheme 2, Table 2). We examined the ad- ture.
dition of O-benzylhydroxylamine to substrate 1b which af-
The enantiomeric excesses increased initially upon
forded only the Michael adduct. All of the reactions were decreasing temperatures to reach a maximum value at
performed under the same conditions, in dichloromethane –40 °C. Reactions performed at lower temperatures gave
using 1.2 equiv. of O-benzylhydroxylamine, 10 mol-% of the lower asymmetric inductions. The Eyring plot shows the
different catalysts at room temperature, and quenched after nonlinear behavior, consisting of two linear regions inter-
10 min. In all cases, total selectivity for the Michael adduct secting at the isoinversion temperature of –40 °C (Figure 1).
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FULL PAPER
Scheme 3. Aza-Michael addition of O-benzylhydroxylamine (2) to α,β-unsaturated N-acyloxazolidinones 1a catalyzed by samarium iodo-
binaphtholate 5.
Table 3. Influence of temperature on the addition of O-benzylhy- Michael reaction and epoxide aminolysis. Negative NLE
droxylamine (2) to 1a catalyzed by samarium iodobinaphtholate 5.
were found for the addition of p-anisidine to N-acyloxazol-
T [°C] % Conv.[a]
3a/4a
% Yield % ee
idinone 1f and for the aminolysis of cyclohexene oxide by
o-anisidine at the isoinversion temperatures.[16c,21] In con-
trast, a strong amplification was observed for the aminoly-
sis of 2,5-dihydrofurane oxide by p-anisidine at +40 °C.
This temperature afforded the highest ee for this reaction.
A study of several epoxide aminolysis reactions, that is, cy-
clohexene oxide and epoxides containing heterocycles with
O- and N-Boc group, by o- and p-anisidine showed that
NLE were substrate dependent. Positive nonlinear effects
were observed for all reactions involving p-anisidine,
whereas negative NLE were obtained for reactions involv-
ing o-anisidine with cyclohexene oxide and dihydrofuran
oxide, but positive NLE with the epoxide containing a ni-
trogen heterocycle. With the aim to detect similar effects for
aza-Michael reactions, we examined the relationship be-
tween the enantiomeric excess of binaphthol and the enan-
tiomeric excess of product 3a resulting from the addition of
O-benzylhydroxylamine to α,β-unsaturated N-acyloxazolid-
inone 1a. The results in Figure 2 indicate a positive nonlin-
ear effect.
Entry Time
[h]
3a
3a[c]
1
2
3
4
5
6
18[b]
18[b]
18[b]
18
64
120
40
20
–20
–40
–60
–76
100
100
100
100
73
70:30
70:30
100:0
100:0
100:0
100:0
33
22
56
84
68
35
23
31
80
88
70
20
49
[a] Conversion (conv.) was determined by NMR spectroscopy.
[b] Unoptimized reaction time. [c] R configuration of 3a was estab-
lished by HPLC by comparison with literature, see ref.[14]
This value was previously obtained for two other reactions
catalyzed by samarium iodobinaphtholate, the aza-Michael
addition of aromatic amines and the aminolysis of epox-
ides.[16b,16c,17] These results suggest that several catalytic
species are involved depending on the temperature.
Figure 1. Eyring plot for aza-Michael addition of 2 to α,β-unsatu-
rated oxazolidinone 1a catalyzed by samarium iodobinaphtholate
5.
Nonlinear variations in enantiomeric excesses of ligands
with that of the products, first observed by Kagan et al. in
the Sharpless epoxidation of geraniol, can be both syntheti-
cally useful and mechanistically informative.[18,19] In a
number of cases the formation of dimeric species explains
Figure 2. NLE for aza-Michael addition of 2 to α,β-unsaturated
oxazolidinone 1a catalyzed by samarium iodobinaphtholate 5 at
–40 °C.
The observation of NLE for the aza-Michael reactions
the nonlinear effects (NLE). In asymmetric reactions cata- involving different α,β-unsaturated N-acyloxazolidinones
lyzed by lanthanides, NLE have frequently been observed and nucleophiles supports a dimeric or more aggregated
and were attributed to the Lewis acidity and the large coor- structure for catalyst 5 as we already proposed.[21] The
dination number of lanthanides. The latter favors self-or- dissociation of homochiral dimers [(R)-5–(R)-5] and [(S)-5–
ganization, aggregation, and self-assemblies of chiral com- (S)-5] under the reaction conditions was also envisioned.
plexes.[20] We have previously studied the relationship be- Equilibrium between the dimers and monomers occurs in
tween the ee of the products and the ee of the samarium the presence of the aromatic amines which can act as li-
iodobinaphtholate for different reactions, such as the aza- gands for samarium. In the aza-Michael reactions involving
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A Catalyst for an Enantioselective Aza-Michael Addition
O-benzylhydroxylamine (2), a similar equilibrium could excess. Aza-Michael addition for substrate 1f was not ob-
take place. As suggested for the aminolysis of epoxides, mo- served at –40 °C. At room temperature and with an excess
nomeric and dimeric species can be considered as active amount of of O-benzylhydroxylamine (3 equiv.), substrate
species for the aza-Michael reactions. For both reactions 1f was transformed into adduct 4f as the sole product. For
the sense of the NLE is dependent on the nature of sub- products 3a–c, enantiomeric excesses were determined by
strates.[22] Positive NLE for the aza-Michael reactions can HPLC, whereas the enantiomeric analyses of 3d and 3e
be attributed to the dissociation of homochiral dimer [(R)- were obtained using proton-decoupled 13C NMR in a poly-
5–(R)-5] into the monomeric species, while the minor en- benzyl-l-glutamate (PBLG)/CD2Cl2 liquid crystal.[23]
antiomer of the catalyst could be trapped as a stable hetero-
Table 4. Enantioselective aza-Michael addition of O-benzylhydrox-
ylamine (2) to α,β-unsaturated N-acyloxazolidinones 1 catalyzed
by samarium iodobinaphtholate 5 at –40 °C.
chiral dimer [(R)-5–(S)-5]. Alternatively a higher activity for
the homochiral dimer than for the heterochiral one can be
assumed. Differences in the activities of [(R)-5–(R)-5] and
Entry
Substrate
% Yield 3
% ee 3
[(R)-5–(S)-5] gave a better explanation for the variation of
the sense of NLE according to the nature of substrates.
Similar phenomena observed for the aminolysis of epoxides
and the aza-Michael reactions support the dimeric struc-
tures previously proposed. These structures A, B, and the
equilibria with monomers are represented in Scheme 4.
As indicated in Table 4 we performed various enantiose-
lective aza-Michael additions using the conditions opti-
mized for the preparation of 3a (Scheme 5). For substrates
1a–c with the alkyl groups or 1d with the ester group at the
terminal position of the double bond, total conversion in
favor of the sole Michael adduct was observed after one
1
2
3
4
5
6
1a (R1 = Me, R2 = H)
1b (R1 = nPr, R2 = H)
1c (R1 = iPr, R2 = H)
1d (R1 = CO2Et, R2 = H)
1e (R1 = Ph, R2 = H)
1f (R1 = H, R2 = CH3)
84
76
59
88[a]
86
52
83
9
83
57[b]
0[c]
[a] The absolute configuration of the major enantiomer (R) of 3a
was assigned by comparison with literature. [b] Reaction performed
at room temperature. At –20 °C, 29% conversion to 3e was ob-
tained with 15% ee. [c] 100% conversion to 4f was observed after
48 h at room temperature using 3 equiv. of 2.
The aza-Michael addition of O-benzylhydroxylamine to
night at –40 °C. Although the presence of a branched chain α,β-unsaturated N-acyloxazolidinones catalyzed by samar-
was detrimental to the enantioselectivity, adducts 3a, 3b, ium iodobinaphtholate compared well with results of sim-
and 3d were isolated with enantiomeric excesses over 80%. ilar reactions with aromatic amines (Scheme 6). The aza-
Aza-Michael addition for substrate 1e substituted with a Michael adduct resulting from substrate 1f, with the methyl
phenyl group afforded product 3e with low conversion at group in the α-position to the carbonyl, was isolated with
–20 and 0 °C, and only a trace amount of product was high enantioselectivity when p-anisidine was employed,[16c]
formed at –40 °C. Performing the reaction at room tem- but could not be isolated when O-benzylhydroxylamine was
perature led to total conversion, but with low enantiomeric used. On the contrary, the addition of O-benzylhydroxyl-
Scheme 4. Proposed dimeric structures A [(R)-5–(R)-5], B [(R)-5–(R)-5], and the transformation into their monomeric species.
Scheme 5. Aza-Michael addition of O-benzylhydroxylamine (2) to α,β-unsaturated N-acyloxazolidinones 1 catalyzed by samarium iodo-
binaphtholate 5.
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D. Didier, A. Meddour, S. Bezzenine-Lafollée, J. Collin
FULL PAPER
ture.[26] N-Alkenoyl oxazolidinones were prepared as described in
the literature.[27] The NMR spectroscopic data were recorded with
360, 300, and 250 spectrophotometers, operating at 360, 300, and
amine (2) to α,β-unsaturated N-acyloxazolidinones 1a and
1b resulted in high enantiomeric excesses, whereas low
enantioselectivities were observed for the addition of aro-
matic amines to these substrates. For substrate 1d, aza-
Michael adducts were selectively prepared with high
enantioselectivity both in the case of p-anisidine and O-
benzylhydroxylamine (2).
1
250 MHz for H NMR and 90, 75, and 62.5 MHz for 13C NMR.
Chemical shifts are given in parts per million (ppm) relative to the
residual signals of the solvent (CDCl3). Infrared spectra were re-
corded with a 1000 FTIR spectrometer and are reported in cm–1.
The samples were in a CDCl3 solution within a KBr cell. Optical
rotations were reported as [α]rDt (c = g/100 mL, solvent). Enantio-
meric excesses (ee) of the products were determined by HPLC
analysis using a Chiralcel OJ and Chiralcel AD-H columns with
iPrOH/hexane mixtures as eluents and comparing to racemic prod-
ucts prepared with SmI2(THF)2. Absolute configuration of aza-
Michael adduct 3a (R) was assigned by comparison with the litera-
ture. The major peak in the HPLC chromatograph of 3a was the
first to elute on the Chiralcel AD-H column.[14]
Preparation of Samarium Complex [(R)-1,1Ј-(Bi-2,2Ј-naphthoxide)]-
iodosamarium-bis(tetrahydrofuran) (5): An orange solution of po-
tassium diphenyl methide (0.412 g, 2 mmol) in THF (10 mL) was
slowly added to a magnetically stirred solution of (R)-1,1Ј-bi-
naphthol (0.286 g, 1 mmol) in THF (10 mL). The orange color of
the reaction mixture slowly disappeared, and a white precipitate
was formed. After 2 h, the suspension was added within 5 min to
a suspension of SmI3(THF)3 (0.747 g, 1 mmol) in THF (10 mL).
The reaction mixture first turned homogeneous and light yellow in
color, and then KI appeared as a white precipitate. After stirring
for 18 h, KI was filtered, and the supernatant solution was evapo-
rated under vacuum. The residue was washed with hexane
(3ϫ25 mL) to eliminate the diphenyl methane. After decantation
and evaporation under vacuum, complex 5 was isolated as a light
1
Scheme 6. Comparison between enantioselective aza-Michael ad-
dition of O-benzylhydroxylamine (2) and of p-anisidine to various
α,β-unsaturated N-acyloxazolidinones.
yellow powder (0.506 g, 72% yield). H NMR (250 MHz, CDCl3):
δ = 8.7–6.0 (m, 12 H), 3.97 (l, 8 H), 1.75 (l, 8 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 130–122 (C, Ar), 70.4 (CH2, THF), 25.4
(CH2, THF) ppm.
General Procedure for Aza-Michael Reactions Catalyzed by
SmI2(THF)2: In the glovebox within a Schlenk tube, a solution of
O-benzylhydroxylamine (specified quantity) in CH2Cl2 was added
to SmI2(THF)2 (0.05 mmol, 27 mg). Outside the glovebox after stir-
ring at room temperature for 10 min, a solution of N-acyloxazolid-
inone 1 (0.5 mmol) in CH2Cl2 (0.5 mL) was added. The solution
was stirred at room temperature for the specified time. The reaction
mixture was hydrolyzed with HCl (0.1 m solution) and extracted
with dichloromethane and ethyl acetate. The combined organic lay-
ers were washed successively with saturated solutions of NaHCO3
and NaCl and then dried with MgSO4. The crude products were
purified by preparative thin layer chromatography on silica gel
(heptane/AcOEt/Et3N, 47.5:47.5:5).
Conclusions
We have found that samarium diiodide is a more efficient
catalyst than various metal triflates for the aza-Michael ad-
dition of O-benzylhydroxylamine to α,β-unsaturated N-acyl-
oxazolidinones. Moreover, samarium iodobinaphtholate
catalyzes the enantioselective aza-Michael addition of O-
benzylhydroxylamine to several α,β-unsaturated N-acylox-
azolidinones with high enantiomeric excesses. As the trans-
formations of β-hydroxylamino ether carbonyl compounds
to aziridines[7,24] or to isoxazolines[9b] have been reported,
samarium iodobinaphtholate catalyzed reactions give an
easy access to these new enantiomerically enriched nitrogen
heterocyclic building blocks.
General Procedure for Aza-Michael Reactions Catalyzed by Samar-
ium Iodobinaphtholate 5: In the glovebox within a Schlenk tube, a
solution of O-benzylhydroxylamine (specified quantity) in CH2Cl2
was added to (R)-samarium iodobinaphtholate 5 (0.05 mmol,
35 mg) and molecular sieves (4 Å, 50 mg). Outside the glovebox
after stirring at the desired temperature for 10 min, a solution of
N-acyloxazolidinone 1 (0.5 mmol) in CH2Cl2 (0.5 mL) was added.
The solution was stirred at room temperature for the specified time,
and the reaction mixture was treated as indicated above.
Experimental Section
General Remarks: All manipulations were carried out under an ar-
gon atmosphere using standard Schlenk or glovebox techniques.
Tetrahydrofuran (THF) and hexane were distilled from sodium
benzophenone ketyl and degassed immediately prior to use.
CH2Cl2 and CDCl3 were distilled from CaH2 and degassed imme-
diately prior to use. SmI2 was prepared according to published
methods.[25] SmI3(THF)3 was obtained by treating SmI2 with di-
iodoethane in THF in a 1:0.5 molar ratio at room temperature.
Potassium diphenyl methide was prepared as described in the litera-
(R)-3-[3-(Benzyloxyamino)butanoyl]oxazolidin-2-one (3a):[14] Oil
(117 mg, 84% yield). The ee value of 3a was determined by HPLC
analysis using a Chiralcel OJ column, [hexane/EtOH, 80:20; flow
is 1 mLmin–1; λ = 210 nm; tR = 35.3 min (minor) and 44.3 min
(major)]; 88% ee. [α]2D0 = –2.3 (c = 1.0, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 1.21 (d, J = 6.8 Hz, 3 H, CH3), 2.92 (dd,
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A Catalyst for an Enantioselective Aza-Michael Addition
1
J1 = 16.6 Hz, J2 = 4.5 Hz, 1 H, 1-H), 3.28 (dd, J1 = 16.6 Hz, J2 =
ee. [α]2D0 = –2.4 (c = 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ
7.9 Hz, 1 H, 1-H), 3.65 (m, 1 H, 1-H), 3.85 (m, 2 H, 1-H), 4.27 (m, = 3.27 (dd, J1 = 16.7 Hz, J2 = 5.4 Hz, 1 H, 1-H), 3.55 (dd, J1
=
2 H, 2-H), 4.69 (s, 2 H, 2-H), 7.19–7.41 (m, 5 H, Ar) ppm. 13C
NMR (90 MHz, CDCl3): δ = 18.3, 39.6, 42.4, 53.1, 61.9, 76.5,
127.8, 128.4, 128.5, 137.7, 153.6, 172.1 ppm. MS (IC): m/z (%) =
16.7 Hz, J2 = 8.4 Hz, 1 H, 1-H), 3.77–3.83 (m, 2 H, 2-H), 4.21–
4.27 (m, 2 H, 2-H), 4.55–4.68 (m, 1 H, 1-H), 4.60 (s, 2 H, 2-H),
7.24–7.42 (m, 10 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ =
39.6, 42.4, 61.6, 62.0, 127.8, 128.0, 128.4, 128.6, 137.6, 140.1, 153.6,
279 [M + H]+. FTIR (KBr/CHCl ): ν = 1694 (max.), 1770, 1958,
˜
3
2253, 2923, 2971 cm–1. HRMS: calcd. for C14H19N2O4 279.1340; 171.5 ppm. FTIR (NaCl): ν = (max.) 1454, 1496, 1628, 1695, 1779,
+
˜
found 279.1345.
2924, 3031 cm–1. MS (CI): m/z (%) = 341 [M + H]+, 358 [M +
NH4]+. HRMS: calcd. for C19H20NO4Na+ 363.1321; found
363.1313.
3-[3-(Benzyloxyamino)hexanoyl]oxazolidin-2-one (3b): Oil (116 mg,
76% yield). The ee value of 3b was determined by HPLC analysis
using a Chiralcel OJ column, [hexane/EtOH, 90:10; flow is
1 mLmin–1; λ = 210 nm, tR = 36.0 min (major) and 40.9 min
(minor)]; 86% ee. [α]2D0 = –1.8 (c = 1.0, CHCl3). 1H NMR
(360 MHz, CDCl3): δ = 0.94 (t, J = 7.2 Hz, 3 H), 1.38–1.58 (m, 4
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra of 3a, 3b, 3c, 3d, and 3e; HPLC
chromatograms of 3a, 3b, and 3c; 1D WINNMR deconvolution
for 3d.
H), 2.91 (dd, J1 = 16 Hz, J2 = 3.9 Hz, 1 H, 1-H), 3.23 (dd, J1
=
16 Hz, J2 = 8.5 Hz, 1 H, 1-H), 3.44–3.58 (m, 1 H, 1-H), 3.71–3.87
(m, 2 H, 2-H), 4.17–4.30 (m, 2 H, 2-H), 4.66 (s, 2 H, 2-H), 7.27–
7.37 (m, 5 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.1,
19.4, 34.5, 38.2, 42.4, 57.5, 61.9, 76.3, 127.7, 128.3, 128.5, 137.8,
Acknowledgments
We thank the Centre National de la Recherche Scientifique
(CNRS) and the Ministère de l’Education Nationale de l’Enseigne-
ment Supérieur et de la Recherche for financial support.
153.7, 172.5 ppm. FTIR (NaCl): ν = 1455 (max.), 1689, 1779, 2873,
˜
2931, 2959 cm–1. MS (ESI): m/z (%) = 307 [M + H]+. HRMS:
+
calcd. for C16H23N2O4 307.1652; found 307.1661.
3-[3-(Benzyloxyamino)-4-methylpentanoyl]oxazolidin-2-one (3c): Oil
(90 mg, 59% yield). The ee value of 3c was determined by HPLC
analysis using a Chiralcel AD-H column, [hexane/EtOH, 90:10;
flow is 1 mLmin–1; λ = 204 nm, tR = 43.5 min (major) and 65.1 min
(minor)]; 52% ee. [α]2D0 = –1.0 (c = 1.0, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 0.96 (d, J = 6.8 Hz, 3 H, CH3), 0.99 (d, J
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= 6.8 Hz, 3 H, CH3), 1.91–2.02 (m, 1 H, 1-H), 2.92 (dd, J1
=
15.5 Hz, J2 = 3.2 Hz, 1 H, 1-H), 3.22 (dd, J1 = 15.5 Hz, J2 = 9.5 Hz,
1 H, 1-H), 3.32–3.40 (m, 1 H, 1-H), 3.70–3.85 (m, 2 H, 2-H), 4.02–
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63.0, 76.0, 127.7, 128.2, 128.5, 137.8, 153.7, 172.9 ppm. FTIR
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˜
m/z (%) = 307 [M + H]+. HRMS: calcd. for C16H23N2O4
+
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307.1659; found 307.1658.
Ethyl 2-(Benzyloxyamino)-4-oxo-4-(2-oxooxazolidin-3-yl)butanoate
(3d): Oil (139 mg, 83% yield). The ee value of 3d was determined
by proton-decoupled 13C NMR spectroscopy in a PBLG/CD2Cl2
liquid crystal at 285 K (sample composition in mg is PBLG/3d/
CD2Cl2, 151.0:53.1:356.5). Deconvolution of the signals at δ =
154.13 ppm (major enantiomer) and 154.07 ppm (minor enantio-
mer), performed using a 1D WINNMR deconvolution routine, led
to a 83% ee. [α]2D0 = –8.0 (c = 1.0, CHCl3). 1H NMR (360 MHz,
CDCl3): δ = 1.28 (t, J = 7.2 Hz, 3 H, CH3), 3.31 (dd, J1 = 17.5 Hz,
J2 = 6.8 Hz, 1 H, 1-H), 3.42 (dd, J1 = 17.5 Hz, J2 = 5.7 Hz, 1 H,
1-H), 3.94 (t, J = 7.0 Hz, 2 H, 2-H), 4.12 (t, J = 6.0 Hz, 1 H, 1-H),
4.22 (q, J = 7.2 Hz, 2 H, CH2OEt), 4.35 (t, J = 7.0 Hz, 2 H, 2-H),
4.70 (s, 2 H, 2-H), 7.30–7.38 (m, 5 H, Ar) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.1, 35.2, 42.3, 59.6, 61.4, 62.1, 76.4, 127.8,
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128.3, 128.6, 137.6, 153.4, 170.4, 171.6 ppm. FTIR (NaCl): ν =
˜
1456 (max.), 1668, 1728, 1782, 2982 cm–1. MS (ESI): m/z (%) =
337 [M + H]+. HRMS: calcd. for C16H21N2O6 337.1394; found
+
337.1399.
3-(Benzyloxyamino)-3-(3-phenylpropanoyl)oxazolidin-2-one (3e): Oil
(97 mg, 57% yield). The ee of 3e was determined by proton-decou-
pled 13C NMR spectroscopy in a PBLG/CD2Cl2 liquid crystal at
285 K (sample composition in mg is PBLG/3e/CD2Cl2,
151.0:53.1:356.5). Deconvolution of the signals at δ = 128.04 ppm
(major enantiomer) and 128.00 ppm (minor enantiomer), per-
formed using a 1D WINNMR deconvolution routine, led to a 7%
Eur. J. Org. Chem. 2011, 2678–2684
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2683

D. Didier, A. Meddour, S. Bezzenine-Lafollée, J. Collin
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Received: January 11, 2011
Published Online: March 30, 2011
2684
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2678–2684