31P-Labeled pyrroline N-oxides: Synthesis of 5-diethylphosphono-5- methyl-1-pyrroline N-oxide (DEPMPO) by oxidation of diethyl (2- methylpyrrolidin-2-yl)phosphonate

Article abstract of DOI:10.1055/s-1999-3626

The synthesis of DEPMPO from diethyl (2-methylpyrrolidin-2- yl)phosphonate (3), prepared by the addition of diethyl phosphite to 2- methylpyrroline, was carried out using different oxidation reagents: H₂O₂, m-CPBA, Oxone, 2-phenylsulfonyl-3-phenyloxaziridine (PSPO), dimethyldioxirane (DMD) and N-methylmorpholine N-oxide with catalytic amounts of tetrapropylammonium perruthenate (NMO/TPAP). The highest yield of DEPMPO (>80%) was obtained using two equivalents of PSPO or DMD. Different compounds involved in the oxidation of 3 have been isolated and characterized.

Full text of DOI:10.1055/s-1999-3626

2036
PAPER
31P-Labeled Pyrroline N-Oxides: Synthesis of 5-Diethylphosphono-5-methyl-
1-pyrroline N-Oxide (DEPMPO) by Oxidation of Diethyl (2-Methylpyrrolidin-
2-yl)phosphonate
Stéphane Barbati,a Jean-Louis Clément,a Claudine Fréjaville,a Jean-Claude Bouteiller,a Paul Tordo,*a
Jean-Claude Michel,b Jean-Claude Yadanb
a Laboratoire SREP, Case 521, CNRS-UMR 6517 "Chimie, Biologie et Radicaux Libres" Université de Provence, Centre de St Jérôme,
F-13397 Marseille Cedex 20, France
b Oxis Int. SA, Research Center, 2, avenue des Coquelicots, F-94385 Bonneuil-sur-Marne, France
Fax +33(4)91988512; E-mail: paul@srepir1.univ-mrs.fr
Received 10 February 1999; revised 5 July 1999
that significant amounts of very pure traps could be need-
Abstract: The synthesis of DEPMPO from diethyl (2-methylpyrro-
ed to perform spin trapping or ESR imaging experiments
lidin-2-yl)phosphonate (3), prepared by the addition of diethyl
on cell cultures, perfused organs or whole animals, we
worked out a satisfactory synthesis of DEPMPO.
phosphite to 2-methylpyrroline, was carried out using different ox-
idation reagents: H2O2, m-CPBA, Oxone, 2-phenylsulfonyl-3-phe-
nyloxaziridine (PSPO), dimethyldioxirane (DMD) and N-
methylmorpholine N-oxide with catalytic amounts of tetrapropyl-
ammonium perruthenate (NMO/TPAP). The highest yield of
DEPMPO (>80%) was obtained using two equivalents of PSPO or
DMD. Different compounds involved in the oxidation of 3 have
been isolated and characterized.
Results and Discussion
Synthesis of Diethyl (2-Methylpyrrolidin-2-yl)phos-
phonate (3)
Key words: aminophosphorylation, secondary amines, oxidations,
nitrones, heterocycles, spin label, phosphorus, additions
The synthesis of 3 was performed from 5-chloropentan-2-
one 1 (Scheme 1). However, 3 was always accompanied
by a significant amount of diethyl 1-cyclopropyl-1-ami-
noethylphosphonate (4). Compound 4 was identified by
comparison with an authentic sample obtained by bub-
Introduction
Most b-phosphorylated five-membered ring nitroxides bling ammonia into an ethanolic solution of acetylcyclo-
possess a large ESR phosphorus coupling which is strong- propane (5) and diethyl phosphite. Formation of 4 during
ly dependent on the ring conformation and constitute a the aminophosphorylation of 1 could be explained by the
very sensitive structural probe.1, 2 In order to facilitate the addition of diethyl phosphite to an intermediate enamine
identification of spin adducts produced in spin trapping (Scheme 1).
experiments it was thus tempting to design new pyrroline
N-oxide spin traps to generate spin adducts bearing a b-
Addition of phosphite to the double bond of an imine is a
usual procedure to generate open-chain aminophospho-
phosphorus substituent. We recently prepared the 5-dieth-
nates,5 and we have now showed that this approach was
ylphosphono-5-methyl-1-pyrroline N-oxide (DEPMPO),
appropriate to prepare large amounts of pure 3. Stirring 2-
and clearly established3 that it was a very promising trap,
methylpyrroline (2) for 7 days with a slight excess of di-
particularly to investigate oxygen free radical processes
ethyl phosphite led to 3 in 98% yield (Scheme 1). 31P, 13C
in biology. Since many researchers4 are now using
and 1H NMR data showed that the purity of 3 obtained in
DEPMPO to trap free radicals in biological milieu and
Scheme 1
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31P-Labeled Pyrroline N-Oxides: Synthesis of 5-Diethylphosphono-5-methyl-1-pyrroline N-Oxide
2037
this way was very good and the compound was used with- led to the exclusive formation of DEPMPO (83% isolated
out further purification in the subsequent oxidation step.
yield) even in the presence of an excess of PSPO (Table).
Dimethyldioxirane (DMD)
Dimethyldioxirane (DMD) is a good oxidizing agent
which has been used to oxidize various organic com-
pounds.10 Murray10c reported that DMD can be used for a
smooth one-step synthesis of C-arylnitrones. Acetone so-
lutions of DMD were prepared and titrated (0.07 M–0.12
M) according to Adam’s procedure.11 The oxidation of an
acetone solution of 3 during 20 min at 0 °C with 1 or 2
equivalents of DMD led respectively to the hydroxyl-
amine 6 (75% isolated yield)12 and to the DEPMPO (80%
isolated yield). With an excess of DMD the formation of
the hydroxamic acid 9 was observed (Scheme 2). Very
good yields of DEPMPO were obtained by oxidizing 6
with molecular oxygen in the presence of a catalytic
amount of copper acetate (81% yield in aqueous ammonia
and 90% in acetonitrile) (Table). Different attempts were
made to oxidize 3 with DMD generated in situ from oxi-
dation of acetone by Oxone as described by
Murray.14c,14f,14 g However, a blue color characteristic of
nitroso compounds rapidly developed in the reaction mix-
ture. Oxone acted as a competitive oxidant favoring the
overoxidation of DEPMPO into 10 and 11 (Scheme 2).
Oxidation of Diethyl (2-Methylpyrrolidin-2-yl)phos-
phonate (3)
m-Chloroperbenzoic Acid (m-CPBA)
The oxidation of 3 with m-CPBA yielded DEPMPO in ap-
proximately 50% yield and has been described else-
where.3 This reagent promoted the formation of side
products 10 and 11 resulting from the overoxidation of
DEPMPO (Table). During the course of the oxidation, a
sample removed from the reaction mixture exhibited an
intense ESR signal (aN, 1.419 mT; aP, 4.950 mT; aHb1
,
,
,
1.907 mT; aHb2, 1.839 mT; aHg, 0.047 mT (3H); aHg1
0.037 mT; aHg2
,
0.040 mT; aHg3
,
0.027 mT; aHg4
0.011 mT) which was also observed with other oxidation
reagents (DMD, PSPO and Oxone). This ESR signal was
assigned to the nitroxide 6∑ (Scheme 2) and the same
spectrum was observed for an authentic sample of 6∑ pre-
pared by reducing DEPMPO with NaBH4 in the presence
of molecular oxygen.
Davis’ Reagent or 2-Phenylsulfonyl-3-phenyloxaziri-
dine (PSPO)
N-Methylmorpholine N-Oxide/Tetrapropylammoni-
um Perruthenate (NMO/TPAP)
The Davis’ reagent6 has been used by Zajac et al. to oxi-
dize amines.7 They found that primary and tertiary amines
led essentially to nitroso and N-oxide compounds respec-
tively, while with secondary amines, mixtures of hydrox-
ylamines and nitrones were obtained. The precursor of 2-
phenylsulfonyl-3-phenyloxaziridine (PSPO), N-ben-
zylidenebenzenesulfonamide, was obtained as described
by Jennings and Lovely8 and was oxidized to PSPO with
Oxone according to the procedure of Davis et al.9 The ox-
idation of 3 was carried out in chloroform at 0 °C by the
dropwise addition of 2 equivalents of PSPO. The reaction
Recently Goti et al. have used this reagent to oxidize
either secondary amines to imines13 or hydroxylamines to
nitrones.14 The experimental procedure used by Goti et al.
was applied to the oxidation of pyrrolidine 3 and hydrox-
ylamine 6 and yielded the corresponding imine 7 (85%
yield) and DEPMPO (76% yield), respectively (Scheme
2). The conversion of imines to the corresponding ni-
trones has been reported using permanganate ions,15 diox-
iranes,16 oxaziridinium tetrafluoroborates17 as oxidizing
reagents. In some instances the formation of the nitrone
Table Products Observed During the Oxidation of 3, 8 and DEPMPO with Different Oxidants
Substrates
Oxidizing
Agents
Equiv Solvents
Products (%)a
3
6
7
DEPMPO
8
9
10
11
3
m-CPBA
2.0
H2O/
10
–
–
88(60)
–
–
–
–
Et2O
PSPO
DMD
2.0
1.0
2.0
3.0
1.0
1.0
2.0
3.0
1.0
1.0
CHCl3
acetone
acetone
MeCN
Buffer
MeCN
CHCl3
CHCl3
CHCl3
CHCl3
–
14
–
–
–
–
–
100(83)
11
91(81)
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
75(63)
4
–
43
–
–
–
–
–
5
TPAP/NMO
Oxone
8
92(85)
–
–
–
–
78
65
–
–
–
–
–
–
–
–
–
–
23(39)b
25(22)b
9
6
Cu2+, air
m-CPBA
(90)
–
–
–
–
–
14
4
–
8
31(22)
–
–
DEPMPO
DMD
–
–
95(67)
–
5
7
m-CPBA
5
95(57)
–
a Estimated yields by 31P NMR. Yields of isolated products are given in parenthesis.
b Yields of isolated products after having completed the oxidation in aerated MeCN solution of Cu(OAc)2.
Synthesis 1999, No. 12, 2036–2040 ISSN 0039-7881 © Thieme Stuttgart · New York

2038
S. Barbati et al.
PAPER
Scheme 2
occurs through the isomerization of the corresponding ox- by the formation of overoxidation products except when
aziridine.18 The oxidation of 7 with m-CPBA led to ox- PSPO was used. The use of 1 equivalent of DMD yielded
aziridine 8 (Scheme 2). However, all attemps to isomerize the hydroxylamine 6 which can be isolated and easily ox-
8 to DEPMPO, following procedures reported in the liter- idized to DEPMPO. On industrial scale, Na2WO4-cata-
ature 18d,19failed.18f
lyzed oxidation with H2O2 has been the most efficient
method for obtaining DEPMPO.
Hydrogen Peroxide/Sodium Tungstate (H2O2/
Na2WO4)
31P NMR spectra were recorded at 40.53 MHz (Bruker AC 100
1
spectrometer) with 85% H3PO4 as external reference. H and 13C
Among the different oxidizing reagents used to oxidize
secondary amines to nitrones, hydrogen peroxide20 is one
of the most commonly used and appeared as the most
appropriate to develop a large scale preparation of DEP-
MPO. Na2WO4-catalyzed oxidation of 3 with hydrogen
peroxide in water led smoothly to DEPMPO in quantita-
tive yield, which was then purified by column chromatog-
raphy on silica gel and molecular distillation. This two-
step purification is essential for obtaining highly purified
DEPMPO.
NMR spectra were recorded on Bruker AC 200 and AM 400X in-
struments respectively, at 200 or 400 MHz and 50.32 or 100.61
MHz. ESR spectra were recorded using an ESP-300 Bruker spec-
trometer operating at 9.5 GHz microwave frequency with 100 KHz
modulation frequency. The purity of DEPMPO was checked by
HPLC. HPLC was performed by using a Waters model 600E multi-
solvent delivery system with a Pye Unicam PU 4021 photodiode ar-
ray detector, a Spectra Physic SP4600 integrator and a Shandon
Ultrabase C18 column (25 cm length 4.6 i.d.). HPLC column con-
ditions were as follows: flow rate, 1.0 mL/min; injection volume 20
mL (solution 10% in eluent solvent); gradient elution programmed
from 4 to 15% A in 15 min, with 10% in B (solvent A: MeOH; sol-
vent B: 2% Et3N, 80% MeOH, 18% H2O; solvent C: H2O). The UV
detector was set between 210 and 320 nm. DEPMPO retention time:
6.60 min.
Conclusion
Molecular distillation: KDL1 apparatus (UIC Society, Germany).
Tvap = 100 °C; Condenser: 5–10 °C; Pressure: 0.001 mbar; flow:
100 droplets/h; stirrer: 400 rpm.
We have shown that the addition of diethyl phosphite
to pyrroline 2 was very efficient and led to almost quanti-
tative yields of the b-phosphorylated pyrrolidine 3.
In a laboratory scale, five different oxidizing reagents
(m-CPBA, PSPO, DMD, Oxone and NMO/TPAP) were
used to oxidize 3. The nitrone DEPMPO was formed with
Diethyl (2-Methylpyrrolidin-2-yl)phosphonate (3)
A mixture of 2-methylpyrroline (2; 10.9 g, 0.13 mol) and diethyl
phosphite (21.7 g, 0.16 mol) was stirred for 7 days at r.t. The prod-
m-CPBA, PSPO, DMD and Oxone, the best yields uct was poured into a 1 N HCl solution (100 mL) and the solution
washed with CH2Cl2 (2 × 80 mL). The aqueous layer was then
basified with aq sat. Na2CO3 and the product extracted with CHCl3
(>80%) and the highest purity being obtained with DMD
and PSPO. The formation of DEPMPO was accompanied
Synthesis 1999, No. 12, 2036–2040 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
31P-Labeled Pyrroline N-Oxides: Synthesis of 5-Diethylphosphono-5-methyl-1-pyrroline N-Oxide
2039
(3 × 100 mL). The organic layer was dried (Na2SO4) and concen-
trated under reduced pressure (0.001 mbar). Pure 3 was obtained as
EtOH/CH2Cl2, 1:9) 7 was obtained as a pale yellow oil (870 mg,
85%). After distillation (57°C, p 0.02 mbar) a colorless oil was ob-
tained (420 mg, 42%).
IR (KBr): n = 2976 (m), 1664 (s), 1246 (m), 1052 (s), 1024 cm-1 (s).
31P NMR (CDCl3): d = 26.72.
1
a colorless oil (28.4 g, 98%) and characterized by H, 13C and 31P
NMR spectra as previously described.3
5-Diethylphosphono-5-methyl-1-pyrroline N-Oxide (DEPM-
PO)
1H NMR (200 MHz, CDCl3): d = 1.33 (t, 3JH,H = 7.0 Hz, 3 H), 1.34
3
3
Oxidation of 3 with Dimethyldioxirane (DMD): An acetone solution
of DMD11 (0.075 M, 200 mL, 2 equiv) was added to a solution of 3
(1.66 g, 7.50 mmol) in acetone (20 mL). The addition was carried
out dropwise at 0 °C under inert atmosphere over 15 min. After stir-
ring the mixture for 5 min was dried (MgSO4), concentrated and
chromatographed (silica gel, EtOH/CH2Cl2,1:9). DEPMPO was ob-
tained as a pale yellow oil (1.43 g, 81% yield).
(t, JH,H = 7.0 Hz, 3 H), 1.50 (d, JH,P = 13.34 Hz, 3 H), 1.40–1.70
(m, 1 H), 2.30–2.60 (m, 1 H), 2.60–2.80 (m, 2 H), 4.10–4.30 (m, 4
H), 7.65 (d, 4JH,P = 4.0 Hz, 1 H).
13C NMR (200 MHz, C6D6): d = 16.52 (d, 3JC,P = 5.8 Hz), 16.58 (d,
3
3JC,P = 5.7 Hz), 23.60, 30.40 (d, JC,P = 4.4 Hz), 37.68, 62.37 (d,
2
1
2JC,P = 7.24 Hz), 62.69 (d, JC,P = 7.3 Hz), 75.97 (d, JC,P = 159.2
Hz), 168.56 (d, 3JC,P = 14.3 Hz).
Large Scale Preparation : Oxidation of 3 with H2O2/Na2WO4: Aq
solution of Na2WO4 (25 g in 1 L, 0.075 M) was mixed with 3 (400
g, 1.81 mol) in a 5-L reactor at 0 °C. A 35% solution of H2O2 (350
mL) was added at 0 °C over 1.5 h. The mixture was kept at 0 °C for
48 h. After filtration of a very fine solid, the filtrate was extracted
with tert-butyl methyl ether (300 mL) and with CHCl3 (4 × 250
mL). The aq phase was saturated with brine (350 g) and then ex-
tracted with CHCl3 (8 × 300 mL). The combined organic phases
were dried (Na2SO4, 300 g) for 12 h. The solvent was removed un-
der reduced pressure below 40 °C. The crude compound was first
purified by column chromatography by small fractions at laboratory
scale (silica gel, CH2Cl2, 1:19). Pure DEPMPO was obtained after
molecular distillation (300 g, 60%).
Anal. calcd for C9H18NO3P•5% H2O (230.7): C 49.11, H 8.29, N
6.36; found C 48.98, H 8.89, N 6.18.
Diethyl (2-Methyl-6-oxa-1-azabicyclo[3.1.0]hex-2-yl)phospho-
nate (8)
A solution of m-CPBA (Jansen 72%, 387 mg, 2.31 mmol) in Et2O
(10 mL) was added dropwise over 15 min to a solution of pyrroline
7 (530 mg, 2.3 mmol) in Et2O (10 mL) at 0 °C. The mixture was
stirred for 30 min and then an aq solution of K2CO3 (15 mL) was
added to the mixture and stirred for 10 min. The organic layer was
washed with a brine (15 mL), dried (Na2SO4), and concentrated un-
der reduced pressure to give a yellow oil. After chromatography
(silica gel, EtOH/CH2Cl2, 1:9) 8 was obtained as a pale yellow oil
(324 mg, 57%) (diastereoisomers were not identified).
Oxidation of 6 with Copper Acetate: A solution of hydroxylamine 6
(765 mg, 3.2 mmol) and Cu(OAc)2 (6.4 mg, 32 mmol) in MeCN (20
mL) was aerated for 30 min. The solution was filtered over Celite
and washed with MeOH/CH2Cl2 (1:4). The organic phase was evap-
orated and the residue chromatographed (silica gel, EtOH/CH2Cl2,
1:9). DEPMPO was obtained as a pale yellow oil (680 mg, 90%).
IR (KBr): n = 2983 (s), 1456 (m), 1246 (s), 1052 (s), 1024 (s) cm-1.
31P NMR (CDCl3): d = 24.17.
1H NMR (200 MHz, CDCl3): d = 1.36 (t, 3JH,H = 7.4 Hz, 6 H), 1.30–
3
1.50 (m, 1 H), 1.54 (d, JH,P = 15.1 Hz, 3 H), 2.00–2.50 (m, 3 H),
4.10-4.30 (m, 4 H), 4.64 (s, 1 H).
Diethyl (1-Hydroxy-2-methylpyrrolidin-2-yl)phosphonate (6)
An acetone solution of dimethyldioxirane11 (0.098 M, 83 mL, 1
equiv) was added dropwise at 0 °C under inert atmosphere over 15
min to a solution of 3 (1.79 g, 8.10 mmol) in acetone (50 mL). After
stirring for 5 min, the mixture was evaporated and stored at –18 °C
overnight. The obtained pale yellow crystals were crystallized from
pentane and stored at 6 °C to afford 1.21 g (63%) of colorless crys-
tals of hydroxylamine 6; mp 39–40 °C.
13C NMR (200 MHz, C6D6): d = 16.40 (d, JC,P = 5.9 Hz), 19.81,
3
2
2
28.04, 28.46, 62.64 (d, JC,P = 7.9 Hz), 62.97 (d, JC,P = 7.3 Hz),
69.25 (d, 1JC,P = 150.6 Hz), 82.79.
Anal. calcd for C9H18NO4P (235.2): C 45.96, H 7.71, N 5.95; found
C 45.43, H 7.78, N 5.68.
References
IR (KBr): n = 3287 (m, br), 2977 (m), 1202 (m), 1056 (s), 1026
cm-1 (s).
(1) (a) Berchadsky, Y.; Kernevez, N.; Le Moigne, F.;
Secourgeon, L.; Tordo, P. UK Patent GB 2 225 015; Chem.
Abstr. 1990, 113, 191636.
31P NMR (CDCl3): d = 27.71.
1H NMR (200 MHz, C6D6): d = 1.09 (t, 3JH,H = 7.1 Hz, 3 H), 1.16 (t,
3JH,H = 7.1 Hz, 3 H), 1.56 (d, 3JH,P = 15.9 Hz, 3 H), 1.40–1.80 (m, 3
H), 2.20–2.60 (m, 1 H), 3.00–3.20 (m, 1 H), 3.40–3.60 (m, 1 H),
3.90–4.40 (m, 4 H).
(b) Le Moigne, F.; Mercier, A.; Tordo, P. Tetrahedron Lett.
1991, 32, 3841.
(c) Mercier, A.; Berchadsky, Y.; Badrudin, Pietri, S.; Tordo,
P. Tetrahedron Lett. 1991, 32, 2125.
(d) Dembkowski, L.; Finet, J. P.; Fréjaville, C.; Le Moigne, F.;
Mercier, A.; Pages, P.; Tordo, P. Free Rad. Res. Comms.
1993, 19, 23.
(e) Stipa, P.; Finet, J. P.; Le Moigne, F.; Tordo, P. J. Org.
Chem. 1993, 58, 4465.
13C NMR (200 MHz, C6D6): d = 16.58 (d, 3JC,P = 5.2 Hz), 16.77 (d,
2
3
3JC,P = 5.7 Hz), 17.78 (d, JC,P = 4.9 Hz), 20.30 (d, JC,P = 5.6 Hz),
33.76, 56.14 (d, 3JC,P = 13.4 Hz), 61.45 (d, 2JC,P = 7.20 Hz), 63.06 (d,
2JC,P = 6.82 Hz), 65.93 (d, 1JC,P = 169.5 Hz).
Anal. calcd for C9H20NO4P (237.2): C 45.54, H 8.50, N 5.90; found
C 45.57, H 8.45, N 5.89.
(2) Tordo, P.; Boyer, M.; Friedmann, A.; Santero, O.; Pujol, L. J.
Phys. Chem. 1978, 82, 1742.
(3) (a) Fréjaville, C.; Karoui, H.; Le Moigne, F.; Culcasi, M.;
Pietri, S.; Tordo, P. French Patent PV 9308906 (1993).
(b) Fréjaville, C.; Karoui, H.; Tuccio, B.; Le Moigne, F.;
Culcasi, M.; Pietri, S.; Lauricella, R.; Tordo, P. J. Chem. Soc.,
Chem. Comm. 1994, 1793.
Diethyl (2-Methylpyrrolin-2-yl)phosphonate (7)
A solution of N-methylmorpholine N-oxide (NMO, 1.6 g, 13.60
mmol) in anhyd MeCN (12 mL) was added under inert atmosphere
at r.t. to a solution of 3 (1.0 g, 4.51 mmol), powdered 4 Å molecular
sieves (2.1 g) and tetrapropylammonium perruthenate (TPAP, 31.8
mg, 0.090 mmol) in anhyd MeCN (13 mL). The mixture was stirred
for 4 h at r.t. The mixture was filtered over Celite and MeCN was
removed under reduced pressure. After chromatography (silica gel,
(c) Fréjaville, C.; Karoui, H.; Tuccio, B.; Le Moigne, F.;
Culcasi, M.; Pietri, S.; Lauricella, R.; Tordo, P. J. Med. Chem.
1995, 38, 258.
(d) Barbati, S.; Clément, J.-L.; Olive, G.; Roubaud, V.;
Synthesis 1999, No. 12, 2036–2040 ISSN 0039-7881 © Thieme Stuttgart · New York

2040
S. Barbati et al.
PAPER
Tuccio, B.; Tordo, P. in Free Radicals in Biology and
Environment, Vol. 27, Nato ASI Series, Series A: Life
Sciences, 1997, p 39.
(12) Barbati, S.; Siri, D.; Tordo, P.; Reboul, J.-P. Acta Cryst. 1997,
C53, 461.
(13) Goti, A.; Romani, M. Tetrahedron Lett. 1994, 35, 6567.
(14) Goti, A.; de Sarlo, F.; Romani, M. Tetrahedron Lett. 1994, 35,
6571.
(4) (a) Karoui, H.; Hogg, N.; Fréjaville, C.; Tordo, P.;
Kalyanaraman, B. J. Biol. Chem. 1996, 271, 6000.
(b) Karoui, H.; Hogg, N.; Joseph, J.; Kalyanaraman, B. Arch.
Biochem. Biophys. 1996, 330, 115.
(15) Christensen, D.; Jørgensen, K. A. J. Org. Chem. 1989, 54,
126.
(c) Guiderelli, A.; Brambilla, L.; Rota, C.; Tomasi, A.;
Cattabeni, F.; Cantoni, O. Biochem. J. 1996, 317, 371.
(d) Roubaud, V.; Sankarapandi, S.; Kuppusamy, P.; Tordo, P.;
Zweier, J. L. Anal. Biochem. 1997, 247, 404.
(5) (a) Fields, E. K. J. Am. Chem. Soc. 1952, 74, 1528.
(b) Ivanova, Z. M.; Kim, T. V.; Suvalova, E. A.; Boldeskul, I.
E.; Gololobov, Y. G. Z. Obshchei Khimii 1976, 46, 236; J.
Gen. Chem. USSR, 1976, 46, 233.
(16) (a) Boyd, D. R.; Coulter, P. B.; McGuckin, M. R.; Sharma, N.
D. J. Chem. Soc., Perkin Trans. 1 1990, 301.
(b) Crandall, J. K.; Reix, T. J. Org. Chem. 1992, 57, 6759.
(17) Hanquet, G.; Lusinchi, X. Tetrahedron 1994, 50, 12185.
(18) (a) Bjørgo, J.; Boyd, D. R.; Campbell, R. M.; Neill, D. C. J.
Chem. Soc., Chem. Commun. 1976, 162.
(b) Boyd, D. R.; Coulter, P. B.; Hamilton, W. J. Tetrahedron
1984, 25, 2287.
(c) Redmore, D. in: Topics in phosphorus Chemistry; Griffith,
E. J.; Grayson, M., Eds.; Vol. 8, Interscience: New York,
1976, pp 515–585.
(c) Davis, F. A.; Sheppard, A. C. Tetrahedron 1989, 45, 5703.
(d) Christensen, D.; Jørgensen, K. A.; Hazell, R. G. J. Chem.
Soc., Perkin Trans 1 1990, 2391.
(d) Issleib, K.; Dopfer, K-P.; Balszuweit, A. Z. Naturforsch.
1981, 36b, 1392.
(e) Afarinkia, K.; Rees, C. W.; Cadogan, J. I. G. Tetrahedron
1990, 46, 7175.
(f) Yager, K.M.; Taylor, C. M.; Smith, A. B. J. Am. Chem.
Soc. 1994, 116, 9377.
(e) Lamchem, M.; In Nitrone Rearrangements, Vol. 1;
Thyagarajan, B. S., Ed.; Wiley: New York, 1968, p 1.
(f) de March, P.; Figueredo, M.; Font, J.; Gallagher, T.; Milán,
S. J. Chem. Soc., Chem. Commun. 1995, 2097.
(19) Lee, T. D.; Keana, J. F. W. J. Org. Chem. 1976, 41, 3237.
(20) (a) Murahashi, S.-I.; Mitsui, H.; Shiota, T.; Tsuda, T.;
Watanabe, S. J. Org. Chem. 1990, 55, 1736.
(b) Sakaue, S.; Sakata, Y.; Nishiyama, Y.; Ishii, Y. Chem.
Lett. 1992, 289.
(g) Hubert, C. Thesis University of Toulouse, France, 1994.
(6) Davis, F. A.; Lamendola, J.; Nadir, U.; Kluger, E. W.;
Sedergran, T. C.; Panunto, T. W.; Billmers, R.; Jenkins, R.;
Turchi, I. J.; Watson, W. H.; Shyong Chen, J.; Kimura, M. J.
Am. Chem. Soc. 1980, 102, 2000.
(c) Ballistreri, F. P.; Chiacchio, U.; Rescifina, A.; Tomaselli,
G. A.; Toscano, R. M. Tetrahedron 1992, 48, 8677.
(d) Murahashi, S.-I.; Imada, Y.; Ohtake, H. J. Org. Chem.
1994, 59, 6170.
(7) Zajac, W. W.; Walters, T. R.; Darcy, M. G. J. Org. Chem.
1988, 53, 5856.
(8) Jennings, W. B.; Lovely, C. J. Tetrahedron Lett. 1988, 29,
3725.
(e) Marcantoni, E.; Petrini, M.; Polimanti, O. Tetrahedron
Lett. 1995, 36, 3561.
(9) Davis, F.A.; Chattopadhyay, S.; Towson, J. C.; Lal, S.; Reddy,
T. J. Org. Chem. 1988, 53, 2087.
(f) Bernetas, R. C.; Adams, G.; Carr, A. A. Tetrahedron Lett.
1996, 37, 6519.
(10) (a) Murray, R. W. Chem. Rev. 1989, 89, 1187.
(b) Murray, R. W.; Singh, M. Synth. Commun. 1989, 19, 3509.
(c) Murray, R. W.; Singh, M. J. Org. Chem. 1990, 55, 2954.
(d) Crandall, J. K.; Reix, T. J. Org. Chem. 1992, 57, 6759.
(e) Brik, M. E. Tetrahedron Lett. 1995, 36, 5519.
(11) Adam, W.; Bialas, J.; Hadjiarapoglou, L. Chem. Ber. 1991,
124, 2377.
(g) Arya, P. Heterocycles 1996, 43, 397.
Article Identifier:
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Synthesis 1999, No. 12, 2036–2040 ISSN 0039-7881 © Thieme Stuttgart · New York