The synthesis of oximes and nitroalkanes bearing a chiral auxiliary unit: Convenient substrates for the preparation of enantiomerically pure nitrile oxides

Article abstract of DOI:10.1016/j.tetasy.2005.05.025

We report the synthesis of four new oximes and three nitroalkanes bearing a chiral unit. All these compounds were converted into nitrile oxides and subjected to 1,3-dipolar cycloaddition with 3-E-hexene, giving the corresponding 2-isoxazolines in fair yie

Full text of DOI:10.1016/j.tetasy.2005.05.025

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 2257–2262
The synthesis of oximes and nitroalkanes bearing a chiral
auxiliary unit: convenient substrates for the preparation
of enantiomerically pure nitrile oxides
a
a
b
a,c
Iwona Kudyba, Julita Jozwik, Jan Romanski, Jerzy Raczko and Janusz Jurczaka,b,
*
´ ´
´
aInstitute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
bDepartment of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland
cZD CHEMIPAN, Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 27 April 2005; accepted 16 May 2005
Available online 28 June 2005
Abstract—We report the synthesis of four new oximes and three nitroalkanes bearing a chiral unit. All these compounds were con-
verted into nitrile oxides and subjected to 1,3-dipolar cycloaddition with 3-E-hexene, giving the corresponding 2-isoxazolines in fair
yields but only with moderate stereoselectivities.
ꢀ 2005 Published by Elsevier Ltd.
1. Introduction
(2R)-bornane-10,2-sultam A, 7,7-dimethylnorbornane-
(1S,2R)-oxazolidinone B, N,N-dicyclohexyl-10-sulfa-
moyl-(2R)-isobornane C, and (1R)-8-phenylmenthol D.
The fifth aldoxime, 2e, was the known derivative of
(1R)-menthol E. Compounds 2a–e are readily available
in high chemical yields (89–93%) by oximation of the
corresponding glyoximides 1a and b or glyoxylates 1c–e
with hydroxylamine hydrochloride (Scheme 1). The anti
configuration of the aldoximes was revealed by their
NMR spectra and proven by X-ray crystallographic
measurements. The results of X-ray studies are pre-
sented in Figures 1–4.
For many years, we have been interested in the applica-
tions of various chiral glyoxylates and glyoximides
bearing different types of auxiliaries to diverse diastereo-
selective processes, such as pericyclic reactions,1 organo-
metallic additions,2 nitroaldol condensations,3 etc.
Recently, we extended the scope of our synthetic interest
to the 1,3-dipolar cycloaddition of nitrile oxides contain-
ing a chiral auxiliary in their structure.
Nitrile oxides are usually generated in situ to avoid the
dimerization process.4 Two convenient substrates for
their synthesis are primary nitroalkanes, easily trans-
formed to nitrile oxides by the Mukayiama and Hoshino
procedure5 or by a broad spectrum of dehydration
agents,6 and aldoximes, treated with halogenating re-
agent/weak base systems7 or with oxidants.8 To our sur-
prise, a literature search revealed only one example for
both classes of these compounds containing the menthyl
residue as an auxiliary.9
Recently, manganese(IV) oxide was found to oxidize
aldoximes to nitrile oxides, which were trapped
in situ with dipolarophiles to afford 2-isoxazolines.10
We have chosen 3-E-hexene as a model dipolarophile.
In our hands, chiral aldoximes reacted slowly and re-
quired the use of a 15-fold excess of MnO2. However,
this afforded the corresponding 2-isoxazolines in fair
yields. We did not observe the aldehydes which usually
form as by products of oxidation (Scheme 2,
Table 1).10
2. Results and discussion
The synthesized aldoximes were in turn very convenient
substrates for the synthesis of other classes of com-
pounds, namely nitroalkanes. Attempts to oxidize the
oximes 2a,b, and e with Oxoneꢁ or the hydrogen perox-
ide–urea complex gave only poor yields of the desired
products, while application of trifluoroperoxyacetic acid
We started our investigations from the synthesis of four
novel aldoximes, 2a–d, derived from the OppolzerÕs
*
Corresponding author. Tel.: +48 22 6320578; fax: +48 22 6326681;
e-mail: jjurczak@chem.uw.edu.pl
0957-4166/$ - see front matter ꢀ 2005Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2005.05.025

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I. Kudyba et al. / Tetrahedron: Asymmetry 16 (2005) 2257–2262
O
O
O
CF3COOOH
NH2OHxHCl
H
H
X*
X*
X*
NO2
O
N
OH
1a
1b
1c
2a
2b
2c
3a
3b
3d
1d
1e
2d
2e
Ph
OH
OH
NH
OH
O
HN
SO2
SO2
N
O
Cx
Cx
A
B
C
D
E
Scheme 1.
Figure 1. X-ray structure of 2-N-glyoxyloyl-(2R)-bornane-10,2-sultam
oxime 2a.
Figure 3. X-ray structure of 2-O-glyoxyloyl-N,N-dicyclohexyl-10-sul-
famoyl-(2R)-isobornane oxime 2c.
Figure 2. X-ray structure of 2-N-glyoxyloyl-7,7-dimethylnorbornane-
(1S,2R)-oxazolidinone oxime 2b.
(prepared using 90% H2O2) afforded the nitroalkanes in
good chemical yields (70–85%).11
The obtained nitroalkanes were converted into the
nitrile oxides using di-tert-butyl dicarbonate and DMAP,
while the nitriles were reacted in situ with the 3-E-hex-
Figure 4. X-ray structure of O-glyoxyloyl-(1R)-menthyl oxime 2e.

I. Kudyba et al. / Tetrahedron: Asymmetry 16 (2005) 2257–2262
2259
O
H
MnO2
X*
CH2CH3
N
O
O
OH
CH3CH2
N
2
X*
X*
O
O
O
Boc2O
DMAP
X*
NO2
3
4
5
Scheme 2.
Table 1.
4.1. General procedure for the preparation of oximes 2
Product
Yield [%]
dea (trans)
To a solution of glyoximide or glyoxylate 1 (1.2 mmol)
and K2CO3 (6 mmol) in a mixture of THF and H2O
5a
5b
5c
5d
5e
5
8
15
55
5
13
(10 ml, 2:1), NH2OH · HCl (2.4 mmol) was added.
9
10
*
The progress of the reaction was monitored by TLC.
When finished, THF was evaporated and the aqueous
phase extracted with CH2Cl2. After drying over MgSO4,
the solvent was evaporated and the residue was purified
on silica gel (hexane/AcOEt 9:1–1:1).
68
70
—
*
—
*Not determined, overlapping of signals.
a Determined by 1H NMR.
4.2. 2-N-Glyoxyloyl-(2R)-bornane-10,2-sultam oxime 2a
ene.12 2-Isoxazolines were readily formed again, but
without real improvement of yields and stereoselectivi-
ties. The described nitroalkanes are also very convenient
substrates for the synthesis of nitro and amino alcohols;
this is currently under investigation in our laboratory.
89% yield. Rf = 0.5hexane/AcOEt 6:4; HRMS-ESI:
calcd for C12H19O4N2S (M+H)+: 287.1060. Found:
287.1073. Anal. Calcd C, 50.33; H, 6.33; N, 9.78; S,
11.20. Found: C, 50.44; H, 6.43; N, 9.59; S, 11.15; IR
(KBr): 3367, 2979, 1678, 1598, 1456, 1336, 1269, 1140,
20
1074, 1002, 884, 762, 543; ½aŠ = À111 (c 1.02, CHCl3);
D
mp = 163 ꢂC (CH2Cl2/hexane); 1H NMR (500 MHz;
CDCl3): d 9.84 (br s, 1H), 8.13 (s, 1H), 4.02 (dd,
J = 5.4, 7.6 Hz, 1H), 3.55 (dAB, J = 13.8 Hz, 1H), 3.48
(dAB, J = 13.8 Hz, 1H), 2.16–1.84 (m, 6H), 1.50–1.30
(m, 2H), 1.17 (s, 3H), 0.99 (s, 3H); 13C NMR
(125MHz; CDCl 3): d 160.0, 141.9, 65.2, 53.2, 48.8,
47.8, 44.8, 38.2, 32.9, 26.3, 20.9, 19.8.
3. Conclusion
In conclusion, four new chiral oximes and three nitro-
alkanes bearing various types of chiral auxiliaries were
synthesized and converted into nitrile oxides, and then
into 2-isoxazolines. Only moderate diastereoselectivities
were obtained. Further investigations including the
application of the other, more sterically demanding ole-
fins are currently in progress.
4.3. 2-N-Glyoxyloyl-7,7-dimethylnorbornane-(1S,2R)-
oxazolidinone oxime 2b
4. Experimental
91% yield. Rf = 0.5hexane/AcOEt 1:1; HRMS-ESI:
calcd for C12H16O4N2Na (M+Na)+: 275.1002. Found:
275.10996. Anal. Calcd C, 56.30; H, 6.30; N, 10.94.
Found: C, 56.46; H, 6.39; N, 10.95; IR (KBr): 3290,
All reactions were carried out under an argon atmo-
sphere with anhydrous solvents dried according to stan-
dard laboratory methods. 1H and 13C NMR spectra
were measured on Bruker AM and Varian Gemini spec-
trometers using residual CHCl3 as the internal reference.
Mass spectra were carried out with AMD-604 Intectra
instrument. Optical rotations were measured on a JAS-
CO DIP-360 polarimeter with a thermally jacketed
10 cm cell. Infrared spectra were recorded on Perkin–
Elmer 1640 FTIR spectrometer. Melting points were
determined with Ko¨fler hot-stage apparatus and are
uncorrected. Flash column chromatography was per-
formed on silica gel (Kieselgel 60, Merck, 200–400
mesh). TLC was performed on Merck aluminum plates
(Kieselgel 60 F254) and compounds were visualized with
a solution of MoO3 and Ce2(SO4)3 in 15% H2SO4.
2961, 1781, 1682, 1597, 1450, 1363, 1173, 1084, 1003,
20
D
776, 763; ½aŠ = +102 (c 1.00, CHCl3); 1H NMR
(400 MHz; CDCl3): d 9.91 (br s, 1H), 8.62 (s, 1H),
4.37 (dd, J = 5.1, 8.1 Hz, 1H), 2.31 (ddt, J = 3.7, 3.6,
13.7 Hz, 1H), 2.12–2.01 (m, 1H), 1.88 (dd, J = 8.1,
13.7 Hz, 1H), 1.87–1.84 (m, 1H), 1.40–1.26 (m, 2H),
1.18 (s, 3H), 1.06 (s, 3H); 13C NMR (100 MHz; CDCl3):
d 161.4, 154.6, 143.1, 85.7, 72.5, 48.5, 42.4, 34.6, 25.9,
25.1, 21.4, 19.0.
In the case of glyoximide 1a, the reaction proceeded without using
potassium dicarbonate.

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I. Kudyba et al. / Tetrahedron: Asymmetry 16 (2005) 2257–2262
4.4. 2-O-Glyoxyloyl-N,N-dicyclohexyl-10-sulfamoyl-
(2R)-isobornane oxime 2c
over MgSO4, the solvents were evaporated, and the res-
idue purified on silica gel (hexane/AcOEt 9:1–1:1).
91% yield. HRMS-ESI: calcd for C24H40O5N2SNa
(M+Na)+: 491.2555. Found: 491.2572. Anal. Calcd C,
61.5; H, 8.5; N, 6.0; S, 6.8. Found: C, 61.5; H, 8.8;
N, 5.9; S, 6.7; IR (KBr): 3242, 3200, 2934, 2852,
4.8. 20-N-(2-Nitroethanoyl)-(20R)-bornane-100,20-sultam
3a
70% yield. Rf = 0.6 hexane/AcOEt 7:3; HRMS-ESI:
calcd for C12H18O5N2SNa (M+Na)+: 325.0829. Found:
325.0829. Anal. Calcd C, 47.67; H, 6.00; N, 9.26; S,
10.61. Found: C, 47.64; H, 6.19; N, 9.28; S, 10.43; IR
1685, 1454, 1327, 1141, 1094, 1025, 981, 771, 573;
20
D
½aŠ = À42.3 (c 1.0, CH2Cl2); mp = 193–195 ꢂC; 1H
NMR (500 MHz; CDCl3): d 8.95(br s, 1H), 7.54 (s,
1H), 5.21–5.15 (m, 1H), 3.27 (dAB, J = 13.0 Hz, 1H),
3.26–3.16 (m, 2H), 2.69 (dAB, J = 13.0 Hz, 1H), 2.06–
1.59 (m, 20H), 1.32–1.18 (m, 5H), 1.12–1.04 (m,
2H), 1.00 (s, 3H), 0.90 (s, 3H); 13C NMR (125
MHz; CDCl3): d 160.6, 142.5, 79.6, 57.5, 53.6, 49.6,
49.1, 44.5, 39.2, 32.8, 32.9, 29.9, 26.9, 26.4, 25.1,
20.4, 19.9.
(KBr): 3405, 2966, 1717, 1566, 1350, 1327, 1272, 1172,
20
D
1138, 868, 825, 530, 481; ½aŠ = À25( c 0.96, CHCl3);
1H NMR (500 MHz; CDCl3): d 5.58 (dAB, J = 14.8 Hz,
1H), 5.50 (dAB, J = 14.8 Hz, 1H), 3.92 (dd, J = 4.9,
7.9 Hz, 1H), 3.54 (dAB, J = 13.9 Hz, 1H), 3.49 (dAB
J = 13.9 Hz, 1H), 2.30–1.75(m, 6H), 1.05–1.25(m,
2H), 1.13 (s, 3H), 0.97 (s, 3H); 13C NMR (125MHz;
,
CDCl3): d 158.9, 77.0, 65.2, 52.3, 49.3, 47.9, 44.4, 37.5,
32.6, 26.2, 20.5, 19.7.
4.5. O-Glyoxyloyl-(1R)-8-phenylmenthyl oxime 2d
93% yield. Rf = 0.4 hexane/AcOEt 7:3; HRMS-
LSIMS(+): calcd for C18H25O3NNa (M+Na)+:
326.17321. Found: 326.17182. Anal. Calcd C, 71.31;
H, 8.31; N, 4.62. Found: C, 71.48; H, 8.13; N, 4.54;
IR (film): 3337, 2956, 2924, 1717, 1444, 1305, 1208,
4.9. 20-N-(2-Nitroethanoyl)-70,70-dimethylnorbornane-
(10S,20R)-oxazolidinone 3b
85% yield. Rf = 0.6 hexane/AcOEt 1:1; HRMS-ESI:
calcd for C12H16O6N2Na (M+Na)+: 291.0951. Found:
291.0945; IR (film): 2966, 1784, 1714, 1565, 1362,
20
1
1014, 759, 700; ½aŠ = À87 (c 1.2, CHCl3); H NMR
D
20
1
(200 MHz; CDCl3): d 8.31 (br s, 1H), 7.29–7.21 (m,
4H), 7.16–7.10 (m, 1H), 6.78 (s, 1H), 4.97 (dt,
J = 10.7, 10.7, 4.5Hz, 1H), 2.08 (ddd, J = 10.7, 14.2,
3.6 Hz, 1H), 1.92–1.86 (m, 1H), 1.79 (dq, J = 13.4, 3.4,
3.4 Hz, 1H), 1.71–1.65 (m, 1H), 1.55–1.44 (m, 1H),
1.32 (s, 3H), 1.23 (s, 3H), 1.15(dq, J = 13.4, 3.4,
3.4 Hz, 1H), 1.09–0.90 (m, 2H), 0.88 (d, J = 6.5Hz,
3H); 13C NMR (50 MHz; CDCl3): d 161.9, 151.7,
142.3, 129.5, 128.5, 125.9, 76.1, 51.1, 42.0, 40.1, 34.9,
31.8, 29.0, 26.9, 24.6, 22.3.
1322, 1079, 765, 668; ½aŠ = +79 (c 0.21, CHCl3); H
D
NMR (500 MHz; CDCl3): d 5.85 (ddAB, J = 15.5 Hz,
1H), 5.62 (ddAB, J = 15.5 Hz, 1H), 4.40 (dd, J = 4.3,
8.2 Hz, 1H), 2.99–2.88 (m, 1H), 2.35–2.30 (m, 1H),
2.14–2.02 (m, 3H), 1.95–1.86 (m, 2H), 1.42–1.32 (m,
2H), 1.16 (s, 3H), 1.06 (s, 3H); 13C NMR (125MHz;
CDCl3): d 161.5, 154.7, 86.0, 78.3, 72.4, 48.4, 42.2,
34.5, 25.7, 25.1, 21.0, 18.9.
4.10. O-(Nitroethanoyl)-(10R)-80-phenylmenthol 3d
4.6. O-Glyoxyloyl-(1R)-menthyl oxime 2e
85% yield. Rf = 0.5hexane/AcOEt 6:4; HRMS-ESI:
calcd for C18H25O4NNa (M+Na)+: 342.1676. Found:
342.1657. Anal. Calcd C, 67.69; H, 7.89; N, 4.38. Found:
72% yield. HRMS-EI: calcd for C12H21O3NNa
(M+Na)+: 250.1419. Found: 250.1439; IR (KBr):
3341, 2958, 2939, 2868, 1726, 1621, 1459, 1311, 1213,
C, 67.57; H, 7.79; N, 4.40; IR (KBr): 3026, 2971, 2919,
20
D
1753, 1566, 1334, 1217, 769, 708; ½aŠ = +80 (c 1.24,
20
1015, 1005, 759, 701; ½aŠ = À87.5( c 1.0, CH2Cl2);
CHCl3); mp = 114 ꢂC (CH2Cl2/hexane); 1H NMR
(400 MHz; CDCl3): d 7.36–7.28 (m, 4H), 7.19–7.15(m,
D
1H NMR (500 MHz; CDCl3): d 9.63 (br s, 1H), 7.55
(s, 1H), 4.90–4.85(m, 1H), 2.07–2.03 (m, 1H), 1.92–
1.83 (m, 1H), 1.73–1.68 (m, 2H), 1.56–1.45 (m, 2H),
1.26–1.04 (m, 2H), 0.93–0.88 (m, 7H), 0.77 (d,
J = 7.0 Hz, 3H); 13C NMR (125MHz; CDCl 3): d
161.8, 142.2, 76.0, 46.8, 40.6, 34.1, 31.4, 26.2, 23.4,
21.9, 20.6, 16.2.
1H), 4.95(dt, J = 11.0, 11.0, 4.8 Hz, 1H), 4.33 (ddAB
,
J = 14.3 Hz, 1H), 4.02 (ddAB, J = 14.3 Hz, 1H), 2.11
(ddd, J = 10.8, 12.3, 3.8 Hz, 1H), 1.96 (dq, J = 13.6,
3.5, 3.5 Hz, 1H), 1.91–1.84 (m, 1H), 1.77–1.70 (m,
1H), 1.56–1.42 (m, 1H), 1.31 (s, 3H), 1.28–1.16 (m,
1H), 1.19 (s, 3H), 1.06–0.93 (m, 2H), 0.90 (d,
J = 6.2 Hz, 3H); 13C NMR (100 MHz; CDCl3): d
161.1, 151.7, 128.1, 125.3, 125.2, 76.8, 75.5, 50.0, 41.2,
39.2, 34.2, 31.2, 30.4, 25.9, 21.7, 21.6.
4.7. General procedure for the preparation of nitroalkanes
3
To
a
precooled solution (0 ꢂC) of (CF3CO)2O
4.11. General procedure for the oxidation of the oximes
(2.5mmol) in acetonitrile (0.5ml), 90% H 2O2 was added
slowly (3.0 mmol), and the reaction mixture stirred for
30 min. The solution of peroxyacid was then slowly
added to a mixture of oxime 2 (1 mmol), urea (0.35
mmol), and Na2HPO4 (5.7 mmol) in acetonitrile
(2 ml). The progress of the reaction was monitored by
TLC. When finished, the phases were separated and
the aqueous phase extracted with CH2Cl2. After drying
To a solution of oxime 2 (1.0 mmol) in CH2Cl2 (5ml),
3 mmol of MnO2, and 3 mmol of 3-hexene were added
at rt. The progress of the reaction was monitored by
TLC and every 3 h, more MnO2 (3 mmol each time)
was added. When finished, the solids were filtered off,
the solvent evaporated, and the residue purified on silica
gel (hexane/AcOEt).

I. Kudyba et al. / Tetrahedron: Asymmetry 16 (2005) 2257–2262
2261
4.12. General procedure for the conversion of nitroalkanes
3 into the nitrile oxides 4
Found: C, 74.8; H, 9.0; N, 3.6; IR (film): 2964, 2876,
1729, 1710, 1580, 1496, 1459, 1309, 1293, 1229, 1157,
20
1125, 938, 765, 701, 563; ½aŠ = À82.5( c 0.68, CH2Cl2);
D
To a solution of di-tert-butyl dicarbonate (1.5mmol), 3-
hexene (5mmol), and DMAP (0.15mmol) in acetoni-
trile (5ml), nitroalkane 3 (1 mmol) in acetonitrile
(3 ml) was slowly added at rt. The progress of the reac-
tion was monitored by TLC and, when finished, the
reaction mixture was evaporated and purified on silica
gel (hexane/AcOEt).
1H NMR (500 MHz; CDCl3): d 7.31–7.10 (m, 5H), 5.02–
4.96 (m, 1H), 4.33–4.26 (m, 1H), 2.54–2.47 (m, 1H),
2.16–1.40 (m, 10H), 1.34 (s, 3H), 1.24 (s, 3H), 1.16–
1.05(m, 2H), 0.95(t, J = 7.0, 3H), 0.88 (s, 3H), 0.84
(t, J = 7.5, 3H); 13C NMR (125MHz; CDCl 3): d 159.8,
153.7, 151.1, 128.0, 125.4, 125.2, 89.9, 76.0, 51.4, 50.2,
41.4, 39.8, 34.4, 31.3, 28.0, 27.5, 26.7, 25.9, 24.0, 21.7,
10.6, 9.2.
4.13. 4,5-Diethyl-2-isoxazoline-3-carboxylic acid (20R)-
N-bornane-100,20-sultam imide 5a
4.17. 4,5-Diethyl-2-isoxazoline-3-carboxylic acid
(1R0)-menthyl ester 5e
HRMS-EI: calcd for C18H28O4N2S (M+H)+: 368.1769.
Found: 368.1764; IR (KBr): 2964, 2939, 1670, 1584,
1459, 1344, 1237, 1170, 1138, 1113, 1062, 932, 756, 539,
HRMS-EI: calcd for C24H36O3N (M+Na)+: 332.2202.
Found: 332.2202; IR (KBr): 3408, 2959, 2934, 2873,
1735, 1711, 1581, 1458, 1388, 1372, 1341, 1315, 1229,
1158, 1122, 1096, 955, 936, 914, 823; 1H NMR
(500 MHz; CDCl3): 4.91–4.85(m, 1H), 4.43–4.39 (m,
1H), 3.12–3.08 (m, 1H), 2.08–2.02 (m, 1H), 1.98–1.85
(m, 1H), 1.81–1.48 (m, 8H), 1.17–1.04 (m, 2H), 0.97 (t,
J = 7.5, 3H), 0.93–0.86 (m, 10H), 0.79–0.77 (m, 3H);
13C NMR (125MHz; CDCl 3): d 160.5, 153.8, 89.7,
76.0, 52.2, 46.7, 40.6, 34.1, 31.4, 28.0, 26.3, 24.0, 23.5,
23.2, 20.7, 16.3, 10.6, 9.1.
1
494; H NMR (500 MHz; CDCl3): d 4.39–4.35(m, 1H),
4.23–4.20 (m, 0.58H), 4.14–4.11 (m, 0.42H), 3.49–3.43
(m, 2H), 3.31–3.27 (m, 0.58H), 3.09–3.06 (m, 0.42H),
2.12–1.84 (m, 5H), 1.76–1.35 (m, 6H), 1.23 (s, 3H), 0.99
(s, 3H), 0.98–0.90 (m, 6H); 13C NMR (125MHz;
CDCl3): d 161.2, 155.7, 89.5, 65.8, 53.1, 52.8, 48.9, 47.9,
4.4, 39.5, 33.3, 28.0, 26.3, 24.0, 21.5, 19.9, 11.2, 9.3.
4.14. 4,5-Diethyl-2-isoxazoline-3-carboxylic acid (20R)-
N-70,70-dimethylnorbornane-(10S,20R)-oxazolidinone
imide 5b
4.18. X-ray data
HRMS-EI: calcd for C18H28O4N2S (M+Na)+: 357.1797.
Found: 357.1790; IR (KBr): 3431, 2966, 2939, 2879,
1791, 1696, 1555, 1458, 1367, 1322, 1303, 1292, 1252,
1229, 1174, 1074, 1051, 1007, 916, 883, 808, 780, 762;
1H NMR (500 MHz; CDCl3): d 4.39–4.35(m, 1H),
3.27–3.23 (m, 1H), 2.83–2.73 (m, 1H), 2.36–2.26 (m,
1H), 2.12–2.02 (m, 1H), 1.92–1.58 (m, 6H), 1.40–1.25
(m, 3H), 1.22 (s, 1.7H), 1.20 (s, 1.3H), 1.07 (s, 3H),
1.02–0.95(m, 6H); 13C NMR (125MHz; CDCl 3): d
162.7, 155.1, 154.1, 89.2, 85.5, 72.6, 54.8, 53.7, 48.2,
42.5, 34.6, 27.8, 25.8, 24.5, 21.5, 19.1, 11.3, 9.1.
X-ray single-crystal diffraction experiments were carried
out on a Kuma KM4CCD j-axis diffractometer using
˚
Mo Ka radiation (0.7107 A). The program used to solve
and refine was SHELX-97.
C12H20N2O5S1 2a, M = 304.36, orthorhombic, a =
8.0503(13), b = 11.5239(16), c = 15.2014(18), a = 90,
b = 90, c = 90ꢂ, space group P212121, Z = 1, Dcalcd
=
0.358 Mg/m3, l(Mo Ka) = 0.063 mmÀ1, 7260 reflections
measured, 3340 [Rint = 0.0966] unique reflections, which
were used in all calculations. Data/restraints/parameters
3340/0/193. The final R1 = 0.0612 (all data), 0À.034(11).
˚
4.15. 4,5-Diethyl-2-isoxazoline-3-carboxylic acid N,N-
dicyclohexyl-100-sulfamoyl-(2R0)-O-isobornane ester 5c
Residual electron density 0. 556 and À0.949 e A
.
C12H16N2O4 2b, M = 252.27, orthorhombic, a =
6.9310(4), b = 8.8942(5), c = 20.0216(11), a = 90, b = 90,
c = 90ꢂ, space group P212121, Z = 4, Dcalcd = 1.358 Mg/
m3, l(Mo Ka) = 0.103 mmÀ1, 17511 reflections mea-
sured, 1925[ Rint = 0.0329] unique reflections, which
were used in all calculations. Data/restraints/parameters
HRMS-EI: calcd for C30H50O5N2SNa (M+Na)+:
573.3338. Found: 573.3334; IR (KBr): 3418, 2933,
2854, 1718, 1455, 1394, 1323, 1227, 1165, 1142, 1106,
1
1048, 981, 941, 853, 823, 773, 642, 576, 524; H NMR
(500 MHz; CDCl3): d 5.12–5.05 (m, 1H), 4.39–4.31 (m,
1H), 3.43 (d, J = 13.0 Hz, 0.45H), 3.41 (d, J = 13.0 Hz,
0.55H), 3.30–3.17 (m, 2H), 3.17–3.10 (m, 0.45H), 3.10–
3.07 (m, 0.55H), 2.63 (d, J = 13.0 Hz, 0.55H), 2.61 (d,
J = 13.0 Hz, 0.45H), 2.08–1.48 (m, 15H), 1.44–1.05 (m,
7H), 1.04 (s, 3H), 0.99–0.91 (m, 5H), 0.88 (s, 3H); 13C
NMR (125MHz; CDCl 3): d 159.9, 153.9, 89.6, 79.7,
57.3, 53.4, 52.6, 49.6, 49.1, 44.5, 39.5, 32.4, 30.2, 28.2,
26.3, 26.1, 25.2, 24.2, 20.4, 20.0, 10.7, 9.1.
1925/0/228. The final R1 = 0.0276 (all data),À30.1(9).
˚
Residual electron density 0.212 and À0.240 e A
.
C24H40N2O5S1 2c, M = 468.64, monoclinic, a = 11.216(2),
b = 9.2187(18), c = 12.435(3), a = 90, b = 96.81(3), c =
90ꢂ, space group P21, Z = 2, Dcalcd = 1.219 Mg/m3,
l(Mo Ka) = 0.162 mmÀ1. The final R1 = 0.0510 (all
data), À0.0À13(15). Residual electron density 0.133 and
˚
À0.128 e A
.
4.16. 4,5-Diethyl-2-isoxazoline-3-carboxylic acid (10R)-
80-phenylmenthyl ester 5d
C12H21NO3 2e, M = 286.35, monoclinic, a = 7.2380(14),
b = 11.293(2), c = 8.7830(18), a = 90, b = 107.23(3),
c = 90ꢂ, space group P21, Z = 2, Dcalcd = 1.101 Mg/m3,
l(Mo Ka) = 0.078 mmÀ1. The final R1 = 0.0390 (all
HRMS-EI: calcd for C24H36O3N (M+H)+: 386.2695.
Found: 386.2687. Anal. Calcd C, 74.8; H, 9.1; N, 3.6.

2262
I. Kudyba et al. / Tetrahedron: Asymmetry 16 (2005) 2257–2262
Chem. 2002, 76, 1595–1600; (c) Czapla, A.; Chajewski, A.;
data), 0.2(18). Residual electron density 0.106 and
˚
À3
´
´
Kiegiel, K.; Bauer, T.; Wielogorski, Z.; Urbanczyk-
Lipkowska, Z.; Jurczak, J. Tetrahedron: Asymmetry
1999, 10, 2101–2111.
À0.108 e A
.
The crystallographic data for the structure reported in
this paper have been deposited with the Cambridge
Crystallographic Data Center as supplementary publica-
tion no. CCDC 269445–269448 for compounds 2b,a,c,
and e, respectively. Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road,
Cambridge CB21EZ, UK [fax: +44 1223 336033; email:
deposit@ccdc.cam.ac.uk].
3. (a) Kudyba, I.; Raczko, J.; Jurczak, J. Tetrahedron Lett.
2003, 44, 8681–8683; (b) Kudyba, I.; Raczko, J.; Jurczak,
J. J. Org. Chem. 2004, 69, 2844–2850; (c) Kudyba, I.;
´
Raczko, J.; Urbanczyk-Lipkowska, Z.; Jurczak, J. Tetra-
hedron 2004, 60, 4807–4820; (d) Kudyba, I.; Raczko, J.;
Jurczak, J. Helv. Chim. Acta 2004, 87, 1724–1736.
4. (a) Gothelf, K. V.; Jørgensen, K. A. Chem. Rev. 1998, 98,
863–909; (b) Frederickson, M. Tetrahedron 1997, 53, 403–
425.
5. Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82,
5339–5342.
6. Maugein, N.; Wagner, A.; Mioskowski, C. Tetrahedron
Lett. 1997, 38, 1547–1550.
Acknowledgements
The authors would like to express thanks to Dr. Ag-
nieszka Szumna for valuable discussions. The X-ray
measurements were undertaken in the Crystallographic
Unit of the Physical Chemistry Laboratory at the Chem-
istry Department of the University of Warsaw.
7. Torsell, K. G. B. Nitrile Oxides, Nitrones and Nitronates in
Organic Synthesis; VCH: Weinheim, 1988.
8. (a) Just, G.; Dahl, K. Tetrahedron 1968, 24, 5251–5269; (b)
Nicolaides, D. N.; Gallos, J. K. Synthesis 1981, 638–640;
(c) Gagneux, A. R.; Meier, R. Helv. Chim. Acta 1970, 53,
1883–1892; (d) Giurg, M.; Młochowski, M. Pol. J. Chem.
1997, 71, 1093–1101.
References
9. (a) Katagiri, N.; Nochi, H.; Kurimoto, A.; Sato, H.;
Kaneko, C. Chem. Pharm. Bull. 1994, 42, 1251–1257; (b)
Herdeis, C.; Syvaeri, J. Arch. Pharm. 1988, 321, 491–
496.
1. (a) Kosior, M.; Asztemborska, M.; Jurczak, J. Synthesis
´
2004, 87–91; (b) Kucharska, A.; Gorczynska, R.; Chapuis,
C.; Jurczak, J. Chirality 2001, 13, 631–633; (c) Jurczak, J.;
Bauer, T. Pure Appl. Chem. 2000, 72, 1589–1596.
´ ´
10. Kiegiel, J.; Popławska, M.; Jozwik, J.; Kosior, M.;
Jurczak, J. Tetrahedron Lett. 1999, 40, 5605–5608.
11. Emmons, W. D.; Pagano, A. S. J. Am. Chem. Soc. 1955,
77, 4557–4559.
2. (a) Kiegiel, K.; Bałakier, T.; Kwiatkowski, P.; Jurczak, J.
Tetrahedron: Asymmetry 2004, 15, 3869–3878; (b) Rasz-
plewicz, K.; Sikorska, L.; Kiegiel, K.; Jurczak, J. Pol. J.
12. Basel, Y.; Hassner, A. Synthesis 1997, 309–312.