Enantioselective synthesis of α,α-disubstituted amines from nitroalkenes

Article abstract of DOI:10.1016/S0957-4166(01)00323-8

Disubstituted nitroalkenes were converted into enantiomerically enriched amines (isolated as their hydrochloride salts) with enantiometric excesses of 88 to >95% in there steps: (a) highly stereoselective conjugate addition of the potassium salt of 4-phenyloxazolidin-2-one; (b) radical-mediated removal of the nitro group; (c) cleavage of the oxazolidinone.

Full text of DOI:10.1016/S0957-4166(01)00323-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1817–1823
Enantioselective synthesis of a,a-disubstituted amines from
nitroalkenes
Mary-Lore`ne Leroux, Thierry Le Gall* and Charles Mioskowski*
CEA-Saclay, Service des Mole´cules Marque´es, Baˆt. 547, 91191 Gif-sur-Yvette Cedex, France
Received 23 February 2001; accepted 15 July 2001
Abstract—Disubstituted nitroalkenes were converted into enantiomerically enriched amines (isolated as their hydrochloride salts)
with enantiomeric excesses of 88 to >95% in three steps: (a) highly stereoselective conjugate addition of the potassium salt of
4-phenyloxazolidin-2-one; (b) radical-mediated removal of the nitro group; (c) cleavage of the oxazolidinone. © 2001 Elsevier
Science Ltd. All rights reserved.
1. Introduction
azolidin-2-one to monosubstituted nitroalkenes and the
conversion of the adducts to enantiomerically pure
1,2-diamines and a-amino acids, owing to the conver-
sion of the nitro group to other functionalities.4 Herein,
we present the enantioselective preparation of a,a-di-
substituted amines from the conjugate adducts of 4-
phenyloxazolidin-2-one to disubstituted nitroalkenes.
Optically active primary amines, in which the nitrogen
atom is attached to a stereogenic center, are important
both as biologically active compounds and synthetic
precursors. Asymmetric syntheses of these products
have been reported, for example from compounds hav-
ing a CꢀN double bond,1 from alkenes via enantioselec-
tive hydroboration,2 or from enamine derivatives via
enantioselective hydrogenation.3
2. Results and discussion
We have previously reported the highly stereoselective
conjugate addition of the potassium salt of 4-phenylox-
Scheme 1 describes our general, three-step strategy to
prepare optically active amines, isolated as their
O
1) tert-BuOK (1.1 equiv.)
18-c-6 (0.2 equiv.)
THF, 0°C, 20 min
O
Ph
R2
O
N
O
Ph
(R)-1
R1
N
2)
NO2
R1
H
NO2
R2
3
2
-78°C, 30 min
1) Li (10 equiv.)
NH3, THF
tert-BuOH (0-10 equiv.)
-78°C, 20 min
Bu3SnH (5 equiv.)
AIBN (0.7 equiv.)
O
4
NH2,HCl
R2
O
Ph
R2
N
R1
toluene, reflux, 2 h
2) HCl, Et2O
R1
1’
4
5
Scheme 1.
* Corresponding authors. E-mail: legall@dsvidf.cea.fr; charles.mioskowski@cea.fr
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00323-8

1818
M.-L. Leroux et al. / Tetrahedron: Asymmetry 12 (2001) 1817–1823
solution of tributyltin hydride in toluene. Compounds
4a–4e were obtained as diastereomerically pure prod-
ucts, hence confirming that a highly stereoselective con-
jugate addition had occurred in the preceding step
(Table 2).
hydrochlorides 5, from nitroalkenes 2. The nitrogen
atom present in the final products derives from oxazo-
lidinone 1, and the absolute configuration of the stereo-
genic center is established in the conjugate addition
step. The nitro group necessary for this addition to
occur is subsequently removed by a radical-mediated
reaction.
A procedure for the conversion of nitroalkanes to
alkanes employing Bu3SnH (0.1 equiv.) as catalyst and
PhSiH3 (1 equiv.) as stoichiometric reducing agent was
recently reported by Fu et al.6 These conditions were
applied to the reduction of compound 3a. However, the
reaction was very sluggish. A better procedure involved
reaction of 3a with 1 equiv. Bu3SnH and 2 equiv.
PhSiH3 for 6 hours in refluxing toluene, which afforded
4a in 56% yield.
The conjugate addition of the potassium salt of 4-
phenyloxazolidin-2-one 1 to disubstituted nitroalkenes
2a–2e (see Section 4 for their preparation) at −78°C in
the presence of 18-crown-6 afforded the corresponding
adducts 3a–3e as mixtures of epimers (Table 1).
At this stage, the absolute configuration of the stereo-
genic center bound to the oxazolidinone was not
known, although it was guessed to be (R) on the basis
of previous results where a like configuration was
observed for all adducts.4
The Birch reduction of compounds 4a–4e was then
performed to cleave the oxazolidinone ring,7 affording
the corresponding amines which were isolated as their
hydrochlorides 5a–5e (Table 3).
Replacement of the nitro group of adducts 3 by a
hydrogen atom to afford oxazolidinones 4 was realized
according to the method developed by Ono et al.5 Thus,
a solution of 3 and AIBN (a,a%-azoisobutyronitrile) in
toluene was slowly added (over 2 hours) to a refluxing
The enantiomeric purity of the final products (from 88
1
to >95%) was assessed by analysis of either the H or
19F NMR spectra of the corresponding amides derived
from the (S)- and (R)-enantiomers of Mosher’s acid
chloride. It was not possible to distinguish between the
two diastereomeric Mosher’s amides derived from com-
pound 5d. The fact that compounds 5a and 5c were not
enantiomerically pure suggests that some racemization
occurred during cleavage of the oxazolidinone moiety.8
Table 1. Yield and epimers ratio of conjugate adducts 3
Product
R1
R2
Epimers
ratio
(%) Yield
3. Conclusion
3a
3b
3c
3d
3e
CH3
C6H11
CH3
CH3
CH3
CH3
80/20
70/30
73
71
69
91
84
Products of the highly stereoselective conjugate addi-
tion of the potassium salt of 4-phenyloxazolidin-2-one
to nitroalkenes are precursors to many enantioenriched,
nitrogen-containing derivatives (Scheme 2). They have
PhCH2CH2 90/10
CH3-CH2
80/20
70/30
PhCH2CH2 CH3
Table 2. Yield, configuration, optical rotation of oxazolidinones 4
Product
R1
R2
Configuration
[h]D (c, CHCl3)
(%) Yield
4a
4b
4c
4d
4e
CH3
C6H11
CH3
CH3
PhCH2CH2
CH3
CH3
PhCH2CH2
CH3–CH2
CH3
(4R,1%R)
(4R,1%S)
(4R,1%R)
(4R,1%R)
(4R,1%S)
−52 (0.53)
79
82
79
70
57
+2.2 (1.15)
−56.9 (1.10)
−49.8 (1.54)
+22.3 (1.21)
Table 3. Yield, configuration, optical rotation, enantiomeric excess of amines hydrochlorides 5
Product
R1
R2
Configuration
[h]D (c, EtOH)
E.e. (%)a
Yield (%)
5a
5b
5c
5d
5e
CH3
C6H11
CH3
CH3
PhCH2CH2
CH3
CH3
PhCH2CH2
CH3–CH2
CH3
(R)
(S)
(R)
(R)
(S)
+1.0 (1.04)
−7.7 (1.00)
+3.0 (0.63)
+6.1 (0.40)
−0.4 (0.68)
88
54
65
70
79
77
\95b
92
c
\95b
a E.e.: Determined by 1H NMR or 19F NMR analysis of the corresponding Mosher’s amides.
b Only one diastereomeric Mosher’s amide seen.
c E.e. not determined, the two diastereomeric Mosher’s amides were not distinguishable.

M.-L. Leroux et al. / Tetrahedron: Asymmetry 12 (2001) 1817–1823
1819
NO2
R2
O
Ph
N
H
R1
O
NH2
NH2
NH2
R1
R1
COOH
(R2 = H)
R2
O
α-amino acid
1,2-diamine
Ph
NO2
N
O
NH2
R1
R2
NH2
R1
OH
R1
R2
R2
β-amino alcool
amine
Scheme 2.
previously been converted to 1,2-diamines and a-amino
acids of high enantiomeric purity. We have demon-
strated that representative chiral, a,a-disubstituted
amines can be prepared asymmetrically, with very good
e.e., in three steps from disubstituted nitroalkenes. The
synthesis of chiral, enantiopure nitrogen-containing
compounds such as alkaloids using this procedure is
now envisaged.
yield the nitroalcohol as
diastereomers. The product was not purified but
employed directly in the next step.
a
mixture of two
4.2.1. 1-Cyclohexyl-2-nitropropan-1-ol. Yield of crude
product: quantitative, yellow oil; two diastereomers
(1:1); 1H NMR (CDCl3):
l 0.75–1.40 (m, 6H,
CH2CH2CH2CH2CH2), 1.60–1.81 (m, 6H, CH2CHCH2,
OH), 1.52 and 1.55 (two d, 3H, CH3, J=5.5 Hz), 3.63
and 3.93 (two m, 1H, CHOH), 4.59–4.74 (m, 1H,
CHNO2).
4. Experimental
4.1. General
4.2.2. 3-Nitro-5-phenylpentan-2-ol. Yield of crude
product: quantitative, yellow oil; two diastereomers
1
(1:1); H NMR (CDCl3): l 1.21 (d, 3H, CH3, J=6.7
THF was distilled from sodium benzophenone ketyl
directly before use. TLC analysis was performed on
Silica Gel 60F254 plates (Merck), with detection by UV
light or with an acidic solution of ninhydrine in tert-
BuOH or with an acidic solution of p-anisaldehyde in
EtOH. Column chromatography was performed using
40–63 mm Merck Silica Gel. IR spectra were recorded
using a Perkin–Elmer 2000 spectrophotometer. Optical
rotations were obtained using a Perkin–Elmer 341
micropolarimeter. Melting points (uncorrected) were
obtained using a Bu¨chi 535 melting point apparatus.
NMR spectra were recorded on a Bruker AM 300
Hz), 2.08–2.47 (m, 2H, CH2CH2Ph), 2.54–2.79 (m, 2H,
CH2Ph), 4.11 and 4.16 (two m, 1H, CHOH), 4.35–4.50
(m, 1H, CHNO2), 7.15–7.35 (m, 5H, Ph-H); 13C NMR
(CDCl3): l 18.73 and 19.38 (CH3), 30.12 and 31.61,
31.70 and 31.80 (CH2CH2Ph), 68.32 and 68.39
(CHOH), 92.07 and 93.40 (CHNO2), 126.30, 126.36,
128.27, 128.50 (Ph-C), 139.59 and 139.79 (ipso-Ph-C).
4.2.3. 4-Nitro-1-phenylpentan-3-ol. Yield of crude
product: quantitative, yellow oil; two diastereomers
1
(1:1); H NMR (CDCl3): l 1.26 and 1.32 (two d, 3H,
1
(300.13, 75.47 and 282.40 MHz for H, 13C and 19F,
CH3, J=6.7 Hz), 2.43–2.57 (m, 2H, CH2CH2Ph), 2.66–
2.75 (m, 2H, CH2Ph), 3.75 and 3.99 (two m, 1H,
CHOH), 4.20–4.45 (m, 1H, CHNO2), 6.95–7.15 (m,
5H, Ph-H).
respectively); Chemical shifts (l) are reported in ppm,
coupling constants (J) are reported in Hz. Mass spectra
were obtained on a Finnegan-Mat 4600 (70 eV).
4.2. General procedure for the preparation of amino
alcohols precursors of nitroalkenes 2
4.3. General procedure for the preparation of nitroal-
kenes 2
To a stirred solution of nitroalkane (1.0 equiv.) in
methanol (50 mL) cooled at 0°C was added a solution
of potassium hydroxide (0.1 equiv.) in methanol (20
mL/mmol). After stirring the mixture for 20 min at
0°C, a solution of aldehyde (1.2 equiv.) in methanol
was added. The reaction mixture was then stirred at
room temperature for 48 h. Acetic acid (0.3 equiv.) was
added. After concentration in vacuo, brine was added
and the mixture was extracted twice with ether. The
combined organic phases were then dried over magne-
sium sulfate, filtered and concentrated in vacuo, to
To a solution of nitroalcohol (1.0 equiv.) in anhydrous
ether (1 mL/mmol) under an argon atmosphere was
added (4-N,N-dimethylamino)pyridine (DMAP), (0.5
equiv.) in acetic anhydride (1.25 equiv.). After stirring
for 48–60 h at room temperature, saturated aqueous
sodium hydrogen carbonate (30 mL) was added. The
phases were separated and the aqueous phase was
extracted with ether (twice). The combined organic
extracts were then washed successively with saturated
aqueous sodium hydrogen carbonate, brine and water,
then dried over magnesium sulfate, filtered and concen-

1820
M.-L. Leroux et al. / Tetrahedron: Asymmetry 12 (2001) 1817–1823
trated in vacuo, the crude product was purified by
chromatography on silica gel, to afford the (E)-
nitroalkene 2.
argon at 0°C for 20 min and then cooled to −78°C. A
solution of nitroalkene 2 (1.0 equiv.) in THF (0.5
mL/mmol) was added dropwise. The reaction mixture
was stirred at −78°C for 30 min, then saturated
aqueous ammonium chloride was added, and the
aqueous phase was extracted with ether (three times).
The combined organic phases were washed with brine,
then dried over magnesium sulfate. After filtration and
concentration in vacuo, the crude product was chro-
matographed on silica gel, to afford nitro compound 3,
as a mixture of two diastereomers.
4.3.1. (E)-2-Nitrobut-2-ene 2a. Yield from 5.0 mL of
1
3-nitrobutan-2-ol: 2.41 g (52%), yellow oil; H NMR
(CDCl3): l 1.87 (d, 3H, CH3CH, J=7.3 Hz), 2.15 (s,
3H, CH3CNO2), 7.19 (q, 1H, CHCH3, J=7.3 Hz); 13C
NMR (CDCl3): l 11.81 (C4), 13.27 (C1), 131.18 (C3),
148.13 (C2); IR (neat) 3000 (wꢀC-H), 1655 (wCꢀC), 1561
(was NO), 1390 (ws NO), 1172 (wC-N) cm−1.
4.3.2. (E)-1-Cyclohexyl-2-nitroprop-1-ene 2b. Yield from
1.67 g of 1-cyclohexyl-2-nitropropan-1-ol: 950 mg
4.4.1. (4R,1%R,2%RS) - 3 - (1% - Methyl - 2% - nitropropyl) - 4-
phenyloxazolidin-2-one 3a. Yield from 563 mg of (E)-2-
nitrobut-2-ene 2a: 1.08 g (73%), colorless oil; two
diastereomers (4/1).
1
(63%), yellow oil; H NMR (CDCl3): l 1.17–1.36 (m,
6H, CH2CH2CH2CH2CH2), 1.57 (s, 1H, CH3), 1.68–
1.80 (m, 5H, CH2CHCH2), 6.97 (d, 1H, -CHꢀ, J=10.0
Hz); 13C NMR (CDCl3): l 12.46 (CH3), 25.18, 25.47,
31.61 (CH2), 37.47 (CHCHꢀ), 140.70 (CHꢀ), 146.10
(CNO2); IR (neat) 2929 (wꢀC-H), 2853 (wC-C cyclohexyl),
1
Major diastereomer: H NMR (CDCl3): l 1.15 (d, 3H,
CH3NCO, J=6.7 Hz), 1.43 (d, 3H, CH3NO2, J=6.7
Hz), 3.54–3.64 (m, 1H, CHNCO), 4.22 (dd, 1H,
CHHO, J=6.7, 8.5 Hz), 4.72 (t, 1H, CHHO, J=8.5
Hz), 4.76 (dd, 1H, CHPh, J=6.7, 8.5 Hz), 5.24–5.33
(m, 1H, CHNO2), 7.32–7.44 (m, 5H, Ph-H); 13C NMR
(CDCl3): l 12.91 (CH3CNO2), 17.15 (CH3CHNCO),
52.41 (CHNCO), 59.95 (CHPh), 70.33 (CH2O), 84.86
(CHNO2), 127.30, 129.28, 129.44 (Ph-C), 137.43 (ipso-
Ph-C), 157.36 (CꢀO); IR (neat) 3066, 3035 (wꢀC-H arom.),
1761 (wCꢀO), 1554 (was NO), 1391 (ws NO), 1249 (wC-O),
1086, 1040 (wC-N) cm−1.
1670 (wCꢀC), 1518 (was NO), 1330 (ws NO), 1112 (wC-N
)
cm−1.
4.3.3. (E)-3-Nitro-5-phenylpent-2-ene 2c. Yield from
1.27 g of 3-nitro-5-phenylpentan-2-ol: 480 mg (48%),
yellow oil; 1H NMR (CDCl3): l 1.56 (d, 3H, CH3,
J=7.3 Hz), 2.86 (m, 4H, CH2CH2), 7.18 (q, 1H,
CHCH3, J=7.3 Hz), 7.19–7.32 (m, 5H, Ph-H); 13C
NMR (CDCl3): l 12.78 (CH3), 28.02 (CH2CH2Ph),
33.39 (CH2Ph), 126.07, 128.18, 128.39 (Ph-C), 132.64
(CH2CHꢀ), 139.95 (ipso-Ph-C), 150.85 (CNO2); IR
(neat) 3085, 3063, 3027 (wꢀC-H arom.), 2933, 2865 (wꢀC-H
aliph.), 1670 (wCꢀC), 1518 (was NO), 1355 (ws NO), 1135
(wC-N) cm−1.
1
Minor diastereomer: H NMR (CDCl3): l 1.11 (d, 3H,
CH3NCO, J=6.7 Hz), 1.44 (d, 3H, CH3NO2, J=6.7
Hz), 3.54–3.64 (m, 1H, CHNCO), 4.15 (dd, 1H,
CHHO, J=6.7, 8.5 Hz), 4.62 (t, 1H, CHHO, J=8.5
Hz), 4.77 (dd, 1H, CHPh, J=6.7, 8.5 Hz), 5.24–5.33
(m, 1H, CHNO2), 7.32–7.44 (m, 5H, Ph-H); 13C NMR
(CDCl3): l 13.43 (CH3CNO2), 16.70 (CH3CHNCO),
53.32 (CHNCO), 59.63 (CHPh), 70.17 (CH2O), 83.60
(CHNO2), 127.30, 129.08, 129.63 (Ph-C), 137.17 (ipso-
Ph-C); IR (neat) 3066, 3035 (wꢀC-H arom.), 1761 (wCꢀO),
1554 (was NO), 1391 (ws NO), 1249 (wC-O), 1086, 1040
(wC-N) cm−1.
4.3.4. (E)-3-Nitropent-2-ene 2d. Yield from 6.0 mL of
1
3-nitropentan-2-ol: 3.84 g (69%), yellow oil; H NMR
(CDCl3): l 1.02 (t, 3H, CH3CH2, J=7.3 Hz), 1.81 (d,
3H, CH3CH, J=7.3 Hz), 2.53 (q, 2H, CH2, J=7.3 Hz),
7.05 (q, 1H, CHCH3, J=7.3 Hz); 13C NMR (CDCl3): l
11.71 (C5), 13.62 (C1), 19.12 (C4), 130.50 (C2), 153.53
(C3); IR (neat) 2986, 2946 (wꢀC-H aliph.), 1643 (wCꢀC), 1560
(was NO), 1355 (ws NO), 1092 (wC-N) cm−1.
4.3.5. (E)-2-Nitro-5-phenylpent-2-ene 2e. Yield from
10.2 g of 4-nitro-1-phenylpentan-2-ol: 5.1 g (54%), yel-
4.4.2. (4R,1%S,2%RS)-3-(1%-Cyclohexyl-2%-nitropropyl)-4-
phenyloxazolidin-2-one 3b. Yield from 837 mg of (E)-1-
cyclohexyl-2-nitroprop-1-ene 2b: 1.32 g (71%), white
solid; two diastereomers (7/3); mp 99.6–100.1°C.
1
low oil; H NMR (CDCl3): l 2.04 (s, 3H, CH3), 2.53
(m, 2H, CH2CH), 2.81 (m, 2H, CH2Ph), 7.15 (t, 1H,
CHCH2, J=6.7 Hz), 7.20–7.37 (m, 5H, Ph-H); 13C
NMR (CDCl3): l 12.00 (CH3), 29.67 (CH2CH2Ph),
34.03 (CH2Ph), 126.23, 128.27, 128.46 (Ph-C), 134.84
(CH2CHꢀ), 140.17 (ipso-Ph-C), 148.00 (CNO2); IR
(neat) 3086, 3063, 3028 (wꢀC-H arom.), 2933, 2861 (wꢀC-H
aliph.), 1673 (wCꢀC), 1522 (was NO), 1334 (ws NO), 1085
(wC-N) cm−1.
1
Major diastereomer: H NMR (CDCl3): l 1.18 (d, 1H,
CH3, J=6.7 Hz), 1.0–2.0 (m, 11H, cyclohexyl-H), 3.32
(dd, 1H, CHNCO, J=4.6, 9.2 Hz), 4.43 (dd, 1H,
CHHO, J=6.1, 9.1 Hz), 4.72 (dd, 1H, CHHO, J=8.5,
9.1 Hz), 4.78 (dd, 1H, CHPh, J=6.1, 8.5 Hz), 5.39 (q,
1H, CHNO2, J=6.7 Hz), 7.25–7.45 (m, 5H, Ph-H); 13C
NMR (CDCl3): l 18.16 (CH3CNO2), 25.91, 25.98,
26.31, 28.96, 31.58, (cyclohexyl-CH2), 41.16 (CHCH-
NCO), 60.66 (CHPh), 63.44 (CHNCO), 69.62 (CH2O),
82.85 (CHNO2), 128.21, 129.37 (Ph-C), 137.01 (ipso-
Ph-C), 157.16 (CꢀO); IR (neat) 3035 (wꢀC-H arom.), 1737
(wCꢀO), 1549 (was NO), 1354 (ws NO), 1240 (wC-O), 1086
(wC-N) cm−1.
4.4. General procedure for the conjugate addition of
(R)-4-phenyloxazolidin-2-one potassium salt to
nitroalkenes 2
A mixture of (R)-4-phenyloxazolidin-2-one (1.1 equiv.),
potassium tert-butoxide (1.1 equiv.) and 18-crown-6
(0.2 equiv.) in THF (7.5 mL/mmol) was stirred under

M.-L. Leroux et al. / Tetrahedron: Asymmetry 12 (2001) 1817–1823
1821
1
Minor diastereomer: H NMR (CDCl3): l 1.50 (d, 1H,
(wꢀC-H arom.), 1752 (wCꢀO), 1551 (was NO), 1362 (ws NO),
1243 (wC-O), 1061, 1038 (wC-N) cm−1.
CH3, J=6.7 Hz), 1.0–2.0 (m, 11H, cyclohexyl-H), 3.50
(dd, 1H, CHNCO, J=9.2, 4.6 Hz), 4.27 (dd, 1H,
CHHO, J=6.1, 9.1 Hz), 4.62 (dd, 1H, CHHO, J=8.5,
9.1 Hz), 4.83 (dd, 1H, CHPh, J=6.1, 8.5 Hz), 5.40 (q,
1H, CHNO2, J=6.7 Hz), 7.25–7.45 (m, 5H, Ph-H); 13C
NMR (CDCl3): l 16.76 (CH3CNO2), 25.92, 25.98,
26.31, 29.35, 31.51 (cyclohexyl-CH2), 39.54 (CHCH-
NCO), 61.76 (CHPh), 62.12 (CHNCO), 70.11 (CH2O),
81.66 (CHNO2), 127.98, 129.12, 129.80 (Ph-C), 137.40
(ipso-Ph-C), 157.91 (CꢀO); IR (neat) 3035 (wꢀC-H arom.),
1737 (wCꢀO), 1549 (was NO), 1354 (ws NO), 1240 (wC-O),
1086 (wC-N) cm−1.
1
Minor diastereomer: H NMR (CDCl3): l 0.90 (t, 3H,
CH3CH2, J=7.3 Hz), 1.10 (d, 1H, CH3CHN, J=6.7
Hz), 1.54–1.94 (m, 2H, CH2CH3), 3.77 (qd, 1H,
CHCH3, J=6.7, 7.3 Hz), 4.13 (dd, 1H, CHHO, J=7.3,
8.5 Hz), 4.54 (t, 1H, CHHO, J=8.5 Hz), 4.76 (dd, 1H,
CHPh, J=7.3, 8.5 Hz), 5.08–5.18 (td, 1H, CHNO2,
J=3.0, 8.5 Hz), 7.25–7.44 (m, 5H, Ph-H); 13C NMR
(CDCl3): l 13.62 (CH3CH2), 13.94 (CH3CHNCO),
24.04 (CH2CH3), 52.51 (CHNCO), 59.66 (CHPh),
70.07 (CH2O), 90.6 1(CHNO2), 127.30, 129.01 (Ph-C),
137.04 (ipso-Ph-C), 157.38 (CꢀO); IR (neat) 3085, 3043
(wꢀC-H arom.), 1752 (wCꢀO), 1551 (was NO), 1362 (ws NO),
1243 (wC-O), 1061, 1038 (wC-N) cm−1.
4.4.3. (4R,1%S,2%RS)-3-(1%-Methyl-2%-nitro-4%-phenylbutyl)-
4-phenyloxazolidin-2-one 3c. Yield from 329 mg of (E)-
3-nitro-5-phenylpent-2-ene 2c: 514 mg (69%), yellow
oil; two diastereomers (9/1).
4.4.5.
(4R,1%S,2%RS)-3-[2%-Nitro-1%-(2-phenylethyl)pro-
pyl]-4-phenyloxazolidin-2-one 3e. Yield from 2.13 g of
(E)-2-nitro-5-phenylpent-2-ene 2e: 3.33 g (84%), yellow
oil; two diastereomers (7/3).
1
Major diastereomer: H NMR (CDCl3): l 1.04 (d, 3H,
CH3, J=6.7 Hz), 1.97–2.05 (m, 2H, CH2CH2Ph), 2.46–
2.65 (m, 2H, CH2Ph), 3.70–3.84 (m, 1H, CHCH3), 4.15
(dd, 1H, CHHO, J=7.3, 8.5 Hz), 4.56 (t, 1H, CHHO,
J=8.5, 9.1 Hz), 4.53 (dd, 1H, CHPh, J=7.3, 9.1 Hz),
5.10 (td, 1H, CHNO2, J=3.7, 9.1 Hz), 7.12–7.35 (m,
10H, Ph-H); 13C NMR (CDCl3): l 13.66 (CH3), 31.68,
32.71 (CH2CH2Ph), 51.99 (CHNCO), 59.59 (CHPh),
70.40 (CH2O), 89.42 (CHNO2), 127.27, 128.40, 128.63,
129.37 (Ph-C), 137.78, 139.63 (ipso-Ph-C), 157.45
(CꢀO); IR (neat) 3063, 3031 (wꢀC-H arom.), 1751 (wCꢀO),
1
Major diastereomer: H NMR (CDCl3): l 1.21 (d, 3H,
CH3, J=6.7 Hz), 1.62–1.84 (m, 1H, CHHCH2Ph),
2.06–2.19 (m, 1H, CHHCH2Ph), 2.54–2.72 (m, 2H,
CH2Ph), 3.60–3.93 (td, 1H, CHNCO, J=3.7, 9.1 Hz),
4.34 (dd, 1H, CHHO, J=6.1, 9.1 Hz), 4.58 (t, 1H,
CHHO, J=9.1 Hz), 4.59 (dd, 1H, CHPh, J=6.1, 9.1
Hz), 5.07 (m, 1H, CHNO2), 7.00–7.40 (m, 10H, Ph-H);
13C NMR (CDCl3): l 17.50 (CH3), 30.05 (CH2CH2Ph),
32.09 (CH2Ph), 55.90 (CHNCO), 60.85 (CHPh), 69.85
(CH2O), 84.47 (CHNO2), 126.20, 127.82, 128.01,
128.46, 129.18 (Ph-C), 137.17, 139.79 (ipso-Ph-C),
157.13 (CꢀO); IR (neat) 3031 (wꢀC-H arom.), 1750 (wCꢀO),
1552 (was NO), 1360 (ws NO), 1242 (wC-O), 1037 (wC-N
)
cm−1.
1
Minor diastereomer: H NMR (CDCl3): l 1.05 (d, 3H,
CH3, J=6.7 Hz), 1.97–2.05 (m, 2H, CH2CH2Ph), 2.46–
2.65 (m, 2H, CH2Ph), 3.70–3.84 (m, 1H, CHCH3), 4.12
(dd, 1H, CHHO, J=7.3, 8.5 Hz), 4.71 (t, 1H, CHHO,
J=8.5, 9.1 Hz), 4.76 (dd, 1H, CHPh, J=7.3, 9.1 Hz),
5.22 (td, 1H, CHNO2, J=3.7, 9.1 Hz), 7.12–7.35 (m,
10H, Ph-H); 13C NMR (CDCl3): l 14.05 (CH3), 31.68,
31.84 (CH2CH2Ph), 52.74 (CHNCO), 59.59 (CHPh),
70.40 (CH2O), 88.90 (CHNO2), 126.56, 127.46, 129.24,
129.54 (Ph-C), 137.78, 139.43 (ipso-Ph-C), 157.45
(CꢀO); IR (neat) 3063, 3031 (wꢀC-H arom.), 1751 (wCꢀO),
1548 (was NO), 1364 (ws NO), 1219 (wC-O), 1036 (wC-N
)
cm−1.
1
Minor diastereomer: H NMR (CDCl3): l 1.46 (d, 3H,
CH3, J=6.7 Hz), 1.62–1.84 (m, 1H, CHHCH2Ph),
2.06–2.19 (m, 1H, CHHCH2Ph), 2.54–2.72 (m, 2H,
CH2Ph), 3.60–3.93 (td, 1H, CHNCO, J=3.7, 9.1 Hz),
4.23 (dd, 1H, CHHO, J=6.1, 9.1 Hz), 4.55 (t, 1H,
CHHO, J=9.1 Hz), 4.79 (dd, 1H, CHPh, J=6.1, 9.1
Hz), 5.23 (m, 1H, CHNO2), 6.90–7.40 (m, 10H, Ph-H);
13C NMR (CDCl3): l 16.73 (CH3), 29.93 (CH2CH2Ph),
32.22 (CH2Ph), 57.42 (CHNCO), 59.66 (CHPh), 70.27
(CH2O), 83.46 (CHNO2), 126.13, 127.46, 128.37,
129.34, 129.53 (Ph-C), 137.78, 139.98 (ipso-Ph-C),
157.58 (CꢀO); IR (neat) 3031 (wꢀC-H arom.), 1750 (wCꢀO),
1552 (was NO), 1360 (ws NO), 1242 (wC-O), 1037 (wC-N
)
cm−1.
4.4.4. (4R,1%S,2%RS)-3-(1%-Methyl-2%-nitrobutyl)-4-phenyl-
oxazolidin-2-one 3d. Yield from 1.28 g of (E)-3-
nitropent-2-ene 2d: 2.72 g (91%), yellow oil; two
diastereomers (4/1).
1548 (was NO), 1364 (ws NO), 1219 (wC-O), 1036 (wC-N
)
cm−1.
1
Major diastereomer: H NMR (CDCl3): l 0.87 (t, 3H,
4.5. General procedure for the reduction of nitro
compounds 3
CH3CH2, J=7.3 Hz), 1.13 (d, 1H, CH3CHN, J=6.7
Hz), 1.54–1.94 (m, 2H, CH2CH3), 3.61 (qd, 1H,
CHCH3, J=6.7, 7.3 Hz), 4.21 (dd, 1H, CHHO, J=7.3,
8.5 Hz), 4.63 (t, 1H, CHHO, J=8.5 Hz), 4.71 (dd, 1H,
CHPh, J=7.3, 8.5 Hz), 5.08–5.18 (td, 1H, CHNO2,
J=3.0, 8.5 Hz), 7.25–7.44 (m, 5H, Ph-H); 13C NMR
(CDCl3): l 9.84 (CH3CH2), 12.91 (CH3CHNCO), 24.14
(CH2CH3), 51.63 (CHNCO), 59.88 (CHPh), 70.23
(CH2O), 91.46 (CHNO2), 127.17, 129.24, 129.40 (Ph-C),
137.36 (ipso-Ph-C), 157.25 (CꢀO); IR (neat) 3085, 3043
A solution of nitro compound 3 (1.0 equiv.) and AIBN
(0.7 equiv.) in toluene (5 mL/mmol) was added drop-
wise over 2 h to a refluxing solution of tributyltin
hydride (5.0 equiv.) in toluene (0.7 mL/mmol), under
an argon atmosphere. The mixture was cooled to room
temperature and concentrated in vacuo. The crude
product was purified by chromatography on silica gel,
to afford the oxazolidinone 4 in pure form.

1822
M.-L. Leroux et al. / Tetrahedron: Asymmetry 12 (2001) 1817–1823
4.5.1. (4R,1%R)-3-(1%-Methylpropyl)-4-phenyloxazolidin-
2-one 4a. Yield from 300 mg of nitro compound 3a: 198
mg (79%), colorless oil; [h]3D0=−52.0 (c 0.53, CHCl3);
1H NMR (CDCl3): l 0.85 (t, 3H, CH3CH2, J=6.7 Hz),
0.87 (d, 3H, CH3CHN, J=7.3 Hz), 1.43–1.81 (m, 1H,
CH2CH3), 3.52–3.64 (m, 1H, CH3CHN), 4.11 (dd, 1H,
CHHO, J=6.1, 8.5 Hz), 4.56 (t, 1H, CHHO, J=8.5
Hz), 4.72 (dd, 1H, CHPh, J=6.1, 8.5 Hz), 7.33–7.37
(m, 5H, Ph-H); 13C NMR (CDCl3): l 11.27 (CH3CH2),
18.68 (CH3CHN), 26.70 (CH2CH3), 52.29 (CH3CHN),
58.57 (CHPh), 70.28 (CH2O), 127.28, 128.93, 129.06
(Ph-C), 140.15 (ipso-Ph-C), 158.17 (CꢀO); IR (neat)
3063, 3034 (wꢀC-H arom.), 1747 (wCꢀO), 1224 (wC-O), 1053,
1043 (wC-N) cm−1; HRMS (EI): [M]+, found 219.1265.
C13H17NO2 requires 219.1259.
(CH3CHN), 58.26 (CHPh), 69.94 (CH2O), 126.98,
128.72 (Ph-C), 139.92 (ipso-Ph-C), 157.77 (CꢀO); IR
(neat) 3033 (wꢀC-H arom.) 2961, 2932, 2873 (wC-H aliph.),
1752 (wCꢀO), 1221 (wC-O), 1044 (wC-N) cm−1; HRMS (EI):
[M]+, found 233.1424. C14H19NO2 requires 233.1416.
4.5.5. (4R,1%S)-3-(1%-Ethyl-3%-phenylpropyl)-4-phenyloxa-
zolidin-2-one 4e. Yield from 500 mg of nitro compound
3d: 250 mg (57%), colorless oil; [h]3D1=+22.3 (c 1.21,
1
CHCl3); H NMR (CDCl3): l 0.88 (t, 3H, CH3, J=7.3
Hz), 1.46 (m, 2H, CH2CH3), 1.52–1.67 (m, 1H,
CHHCH2Ph), 1.67–1.82 (m, 1H, CHHCH2Ph), 2.54 (t,
2H, CH2Ph, J=7.9 Hz), 3.56 (m, 1H, CHNCH2CH3),
4.22 (dd, 1H, CHHO, J=5.5, 8.5 Hz), 4.51 (t, 1H,
CHHO, J=8.5 Hz), 4.54 (dd, 1H, CHPh, J=5.5, 8.5
Hz), 6.92 (d, 2H, ortho-H-PhCH2, J=8.5 Hz), 7.09–
7.25 (m, 3H, meta,para-H-PhCH2), 7.38 (m, 5H, H-
PhCHN); 13C NMR (CDCl3): l 19.09 (CH3), 28.15
(CH2CH3), 32.71 (CH2CH2Ph), 34.52 (CH2Ph), 56.81
(CHEt), 58.39 (CHPh), 69.98 (CH2O), 125.55, 127.40,
127.98, 128.04, 128.88, 128.95 (Ph-C), 139.62, 141.47
(ipso-Ph-C), 158.48 (CꢀO); IR (neat) 3062, 3029 (wꢀC-H
4.5.2. (4R,1%S)-3-(1%-Cyclohexylpropyl)-4-phenyloxazo-
lidin-2-one 4b. Yield from 600 mg of nitro compound
3b: 425 mg (82%), white solid; mp 94.0–95.0°C; [h]3D0=
1
+2.2 (c 1.15, CHCl3); NMR H (CDCl3, l ppm, J Hz)
0.79 (t, 3H, CH3, J=7.3 Hz), 0.70–1.07 (m, 6H,
CH2CH2CH2CH2CH2), 1.45–1.73 (m, 7H, CH2CHCH2,
CH2CH3), 3.10 (m, 1H, CHCHN), 4.22 (dd, 1H,
CHHO, J=6.1, 8.5 Hz), 4.61 (dd, 1H, CHHO, J=8.5,
9.1 Hz), 4.75 (dd, 1H, CHPh, J=6.1, 9.1 Hz), 7.36 (m,
5H, Ph-H); 13C NMR (CDCl3): l 10.90 (CH3), 20.80
(CH2CH3), 25.30, 25.66, 25.82, 29.73, 30.38 (cyclo-
hexyl-CH2), 39.99 (CHCHN), 58.81 (CHPh), 61.76
(CHEt), 69.36 (CH2O), 127.56, 128.43 (Ph-C), 139.20
(ipso-Ph-C), 158.26 (CꢀO); IR (neat) 3067, 3032 (wꢀC-H
arom.), 1732 (wCꢀO), 1224 (wC-O), 1058, 1040 (wC-N) cm−1;
HRMS (EI): [M]+, found 287.1870. C18H25NO2 requires
287.1885.
arom.)1746 (wCꢀO), 1603 (wC-C), 1228 (wC-O), 1042 (wC-N
)
cm−1; HRMS (EI): [M]+, found 309.1723. C20H23NO2
requires 309.1729.
4.6. Reduction of nitro compound 3a by tributyltin
hydride in the presence of phenylsilane
A solution of nitro compound 3a (300 mg, 1.1 mmol,
1.0 equiv.), tributyltin hydride (0.3 mL, 1.1 mmol, 1.0
equiv.), phenylsilane (0.3 mL, 2.3 mmol, 2.0 equiv.) and
AIBN (130 mg, 0.8 mmol, 0.7 equiv.) in toluene (6.5
mL) was stirred under reflux for 6 h under an argon
atmosphere. The mixture was cooled to room tempera-
ture and concentrated in vacuo, the crude product was
purified by chromatography on silica gel (49:1
CH2Cl2:Et2O) to afford oxazolidinone 4a (140 mg,
56%).
4.5.3. (4R,1%R)-3-(1%-Methyl-4%-phenylbutyl)-4-phenylox-
azolidin-2-one 4c. Yield from 460 mg of nitro com-
pound 3c: 317 mg (79%), colorless oil; [h]2D9=−56.9 (c
1
1.10, CHCl3); H NMR (CDCl3): l 0.82 (d, 3H, CH3,
J=6.7 Hz), 1.42–1.79 (m, 4H, CH2CH2CHN), 2.44–
2.70 (m, 2H, CH2Ph), 3.67–3.79 (m, 1H, CH3CHN),
4.09 (dd, 1H, CHHO, J=6.7, 8.5 Hz), 4.51 (t, 1H,
CHHO, J=8.5, 9.1 Hz), 4.54 (dd, 1H, CHPh, J=6.7,
9.1 Hz), 7.15–7.35 (m, 10H, Ph-H); 13C NMR (CDCl3):
l 19.09 (CH3), 28.15 (CH2CHCH3), 32.68, 35.20
(CH2CH2Ph), 50.31 (CHCH3), 58.27 (CHPh), 70.04
(CH2O), 125.75, 127.14, 128.21, 128.34, 128.76, 128.89
(Ph-C), 139.82, 141.89 (ipso-Ph-C), 157.97 (CꢀO); IR
(neat) 3061, 3028 (wꢀC-H arom.), 1748 (wCꢀO), 1224 (wC-O),
1043 (wC-N) cm−1; HRMS (EI): [M]+, found 309.1727.
C20H23NO2 requires 309.1729.
4.7. General procedure for the preparation of amine
hydrochlorides 5
Ammonia was transferred into a flask cooled at −78°C
and equipped with a cold-finger condenser. Small pieces
of lithium (10 equiv.) were added. A solution of oxazo-
lidinone 4 (1.0 equiv.) in THF (75 mL), containing
either tert-butanol (1.0 mL/mmol, reduction of 4a, 4b,
4d) or not (reduction of 4c, 4d) was then added via
syringe to the deep-blue solution. After stirring for 20
min at −78°C, solid ammonium chloride (11.0 equiv.)
was added. The reaction mixture was allowed to warm
to room temperature, the residual ammonia was blown
off under a nitrogen stream. Water was added, then 4N
HCl was added until the mixture was acidic, pH <6.
The aqueous phase was extracted with ether, and the
organic phase was discarded. Dichloromethane was
added to the aqueous phase and 2N NaOH was added
until the mixture had basic pH. The phases were sepa-
rated and the aqueous phase was extracted with
dichloromethane. The combined organic phases were
dried over magnesium sulfate, filtered and partially
concentrated in vacuo. A solution of hydrogen chloride
4.5.4. (4R,1%R)-3-(1%-Methylbutyl)-4-phenyloxazolidin-2-
one 4d. Yield from 500 mg of nitro compound 3d: 300
mg (70%), colorless oil; [h]3D1=−49.8 (c 1.54, CHCl3);
1H NMR (CDCl3): l 0.73 (d, 3H, CH3CHN, J=6.7
Hz), 0.76 (t, 3H, CH3CH2, J=7.3 Hz), 1.06–1.23 (m,
2H, CH2CH3), 1.30–1.42 (m, 1H, CHHCHN), 1.56–
1.68 (m, 1H, CHHCHN), 3.51–3.63 (qd, 1H,
CH3CHN, J=6.7, 8.5 Hz), 3.98 (dd, 1H, CHHO,
J=6.1, 8.5 Hz), 4.46 (t, 1H, CHHO, J=8.5 Hz), 4.66
(dd, 1H, CHPh, J=6.1, 8.5 Hz), 7.25 (m, 5H, Ph-H);
13C NMR (CDCl3): l 13.46 (CH3CH2), 18.64, 19.44
(CH3CHN,
CH2CH3),
35.52
(CH2Et),
50.01

M.-L. Leroux et al. / Tetrahedron: Asymmetry 12 (2001) 1817–1823
1823
in ether was added, the precipitated amine hydrochloride
5 was filtered and dried in a dessiccator.
1H, H3), 7.11–7.30 (m, 5H, Ph-H), 8.41 (broad m, 3H,
NH3 ); 13C NMR (CDCl3): l 9.51 (CH3), 25.53
+
(CH2CH3), 31.19 (CH2CH2Ph), 33.71 (CH2Ph), 53.18
(CHN), 125.97, 128.20, 128.30, 128.43 (Ph-C), 140.17
(ipso-Ph-C); IR (KBr pellet) 3031 (wꢀC-H arom.), 2919,
2634, 2025 (wNH +), 1515 (lNH +), 1024 (wC-N) cm−1; MS
4.7.1. (R)-2-Aminobutane hydrochloride 5a. Yield from
123 mg of oxazolidinone 4a: 33 mg (54%), white solid;
[h]D37=+1.0 (c 1.04, EtOH); lit.:9 [h]2D0=+1.12 (c 13.51,
3
3
1
(CI/NH3, m/z) 164 [M+H+−HCl], 181 [M+NH4 −HCl],
327 [2M+H+−HCl]; HRMS (EI): [M]+, found 163.1339.
C11H17N requires 163.1361.
+
H2O); H NMR (CD3OD): l 0.95 (t, 3H, CH3CH2, J=
7.3 Hz), 1.24 (d, 3H, CH3CHN, J=6.1 Hz), 1.45–1.75 (m,
2H, CH2CH3), 3.14 (m, 1H, CHN); 13C NMR (CD3OD):
l 10.14 (C4), 18.23 (C1), 28.72 (C3), 50.39 (C2); IR (KBr
pellet) 2968, 2005 (wNH +), 1505 (lNH +), 1011 (wC-N) cm−1;
4.8. General procedure for the preparation of Mosher
amides
3
3
MS (CI/NH3, m/z) 74 [M+H+−HCl], 91 [M+NH4 −
+
HCl].
A suspension of amine hydrochloride 5 (1.0 equiv.) in
anhydrous dichloromethane (3 mL/mmol) under an
argon atmosphere was treated sequentially with anhy-
drous pyridine (6 mL/mmol) and then either (R)- or (S)-
a-methoxy-a-trifluoromethylphenylacetic acid chloride
(Mosher’s acid chloride, 1.0 equiv.). The reaction mixture
was stirred under reflux for 1 h. After cooling to room
temperature, ether was added, and the organic phase was
successively washed with aqueous HCl, aqueous 10%
sodium bicarbonate and water, then dried over magne-
sium sulfate. The crude product obtained after filtration
4.7.2. (S)-1-Amino-1-cyclohexylpropane hydrochloride
5b. Yield from 250 mg of oxazolidinone 4b: 100 mg
(65%), white solid; mp 266.0–267.8°C; lit.:10 275–276°C
(EtOH, Et2O); [h]D30=−7.7 (c 1.00, EtOH); lit.:10 [h]D22=
1
−7.2 (c 2.6, EtOH); H NMR (CDCl3): l 1.04 (t, 3H,
CH3, J=7.3 Hz), 1.10–1.26 (m, 6H, CH2CH2CH2-
CH2CH2), 1.62–1.82 (m, 7H, CH2CH3, CH2CHCH2),
2.93 (broad m, 1H, CHN), 8.29 (broad m, 3H, NH3 ); 13
C
+
NMR (CDCl3): l 10.30 (CH3), 23.14 (CH2CH3), 26.15,
28.22, 29.00 (cyclohexyl-CH2), 39.45 (CHCHN), 58.86
(CHN); IR (KBr pellet) 2929, 2027 (wNH +), 1519 (lNH +),
and concentration in vacuo was analyzed by 1H and 19
NMR.
F
3
3
1032 (wC-N) cm−1; MS (CI/NH3, m/z) 142 [M+H+−HCl],
159 [M+NH4 −HCl], 283 [2M+H+−HCl].
+
4.7.3. (R)-2-Amino-5-phenylpentane hydrochloride 5c11.
Yield from 200 mg of oxazolidinone 4c: 90 mg (70%),
white solid; mp 129.3–129.9°C; [h]3D0=+3.0 (c 0.63,
References
1. Recent reviews: (a) Bloch, R. Chem. Rev. 1998, 98, 1407–
1438; (b) Enders, D.; Reinhold, U. Tetrahedron: Asymme-
try 1997, 8, 1895–1946.
1
EtOH); H NMR (CDCl3): l 1.38 (d, 3H, CH3, J=6.7
Hz), 1.60–1.88 (m, 4H, CH2CH2CH2Ph), 2.62 (m, 2H,
CH2Ph), 3.32 (m, 1H, CHN), 7.14–7.28 (m, 5H, Ph-H),
2. Brown, H. C.; Kim, K.-W.; Cole, T. E.; Singaram, B. J.
8.35 (broad m, 3H, NH3 ); 13C NMR (CDCl3): l 18.47
+
Am. Chem. Soc. 1986, 108, 6761–6764.
3. (a) Burk, M. J.; Wang, Y. M.; Lee, J. R. J. Am. Chem. Soc.
1996, 118, 5142; (b) Zhang, F.-Y.; Pai, C.-C.; Chan, A. S.
J. Am. Chem. Soc. 1998, 208, 5808–5809; (c) Zhu, G.;
Zhang, X. J. Org. Chem. 1998, 63, 9590–9593.
4. (a) Lucet, D.; Toupet, L.; Le Gall, T.; Mioskowski, C. J.
Org. Chem. 1997, 62, 2682–2683; (b) Sabelle, S.; Lucet, D.;
Le Gall, T.; Mioskowski, C. Tetrahedron Lett. 1998, 39,
2111–2114; (c) Lucet, D.; Sabelle, S.; Kostelitz, O.; Le Gall,
T.; Mioskowski, C. Eur. J. Org. Chem. 1999, 2583–2591;
(d) Lucet, D.; Heyse, P.; Gissot, A.; Le Gall, T.;
Mioskowski, C. Eur. J. Org. Chem. 2000, 3575–3579.
5. Ono, N.; Miyake, H.; Kaji, A. J. Org. Chem. 1984, 49,
4997–4999.
(CH3), 27.01 (CH2CH2Ph), 34.33, 35.10 (CH2CHN,
CH2Ph), 48.17 (CHN), 125.75, 128.11, 128.17 (Ph-C),
141.21 (ipso-Ph-C); IR (KBr pellet) 2893, 2049 (wNH +),
3
1518 (lNH +), 1030 (wC-N) cmc−1; MS (CI/NH3, m/z) 164
3
[M+H+−HCl], 181 [M+NH4 −HCl], 327 [2M+H+−HCl];
+
HRMS (EI): [M]+, found 163.1355. C11H17N requires
163.1361.
4.7.4. (R)-2-Aminopentane hydrochloride 5d11. Yield from
250 mg of oxazolidinone 4d: 105 mg (79%), white solid;
mp 161.6–162.5°C; [h]3D7=+6.1 (c 0.40, EtOH); 1H NMR
(CDCl3): l 0.93 (t, 3H, CH3CH2, J=7.3 Hz), 1.38 (d, 3H,
CH3CHN, J=6.7 Hz), 1.45 (q, 2H, CH2CH3, J=7.3 Hz),
1.52–1.67 (m, 1H, CHHCHN), 1.72–1.84 (m, 1H,
CHHCHN), 3.32 (m, 1H, CHN), 8.35 (broad m, 3H,
6. Tormo, J.; Hays, D. S.; Fu, G. C. J. Org. Chem. 1998, 63,
5296–5297.
7. Evans, D. A.; Sjogren, E. B. Tetrahedron Lett. 1985, 26,
3783–3786.
NH3 ); 13C NMR (CDCl3): l 13.39 (C5), 18.44, 18.60 (C1,
+
C4), 36.69 (C3), 48.11 (C2); IR (KBr pellet) 2931, 2553
8. The oxazolidinone 1 is not racemized during the formation
of its potassium salt. This was checked in the following
manner: (S)-1 was treated under the usual conditions, then
the oxazolidinone obtained was converted to the Mosher
derivative (from (S)-Mosher’s acid chloride), which was
(wNH +), 1513 (lNH +), 1202,1147 (wC-N) cm−1; MS (CI/
3
3
NH3, m/z) 164 [M+H+−HCl], 181 [M+NH4 −HCl];
HRMS (EI): [M−H]+, found 86.0963. C5H12N requires
86.0970.
+
1
found to be diastereomerically pure by H NMR.
4.7.5. (S)-3-Amino-1-phenylpentane hydrochloride 5e.
Yield from 220 mg of oxazolidinone 4e: 110 mg (77%),
white solid; mp 177.3–179.6°C; [h]3D0=−0.4 (c 0.68,
9. Thome´, L. G. Chem. Ber. 1903, 36, 582.
10. La Manna, A.; Ghislandi, V.; Hulbert, P. B.; Scopes, P. M.
Farmaco Ed. Sci. 1967, 22, 1037–1053.
1
EtOH); H NMR (CDCl3): l 1.00 (t, 3H, CH3, J=7.3
11. For racemic compounds 5c and 5d, see: Gajda, T.;
Napieraj, A.; Osowska-Pacewicka, K.; Zawadzki, S.;
Zwierzak, A. Tetrahedron 1997, 53, 4935–4946.
Hz), 1.74–1.84 (m, 2H, CH2CH3), 1.93–2.15 (m, 2H,
CH2CH2Ph), 2.69–2.88 (m, 2H, CH2Ph), 3.15 (broad m,