Synthesis of the cis diastereoisomer of 5-diethoxyphosphoryl-5-methyl-3- phenyl-1-pyrroline N-oxide (DEPMPPOc) and ESR study of its superoxide spin adduct

Article abstract of DOI:10.1016/j.tetlet.2004.07.016

The cis and trans diastereoisomers of 5-diethoxyphosphoryl-5-methyl-3- phenyl-1-pyrroline N-oxide (DEPMPPO), the C(3)-phenyl analogue of DEPMPO, were prepared in three steps from phenylacetaldehyde and used in ESR-spin trapping of various carbon-, oxygen- and sulfur-centred radicals. In the case of the cis-isomer, the presence of the phenyl group cancels the alternating line width phenomenon observed for the DEPMPO-OOR (R = H, Bu^t) spin adducts. The ESR spectra of the DEPMPPOc-OOR spin adducts exhibit more straightforward patterns and are more easily assignable.

Full text of DOI:10.1016/j.tetlet.2004.07.016

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6385–6389
Synthesis of the cis diastereoisomer of
-diethoxyphosphoryl-5-methyl-3-phenyl-1-pyrroline N-oxide
DEPMPPOc) and ESR study of its superoxide spin adduct
5
(
C e´ line Nsanzumuhire, Jean-Louis Cl e´ ment, Olivier Ouari, Hakim Karoui,
*
Jean-Pierre Finet and Paul Tordo
Laboratoire SREP, UMR 6517 CNRS et Universit e´ s d’Aix-Marseille 1 et 3, Avenue Esc. Normandie Niemen, Marseille 13397, France
Received 15 June 2004; revised 18 June 2004; accepted 5 July 2004
Abstract—The cis and trans diastereoisomers of 5-diethoxyphosphoryl-5-methyl-3-phenyl-1-pyrroline N-oxide (DEPMPPO), the
C(3)-phenyl analogue of DEPMPO, were prepared in three steps from phenylacetaldehyde and used in ESR-spin trapping of various
carbon-, oxygen- and sulfur-centred radicals. In the case of the cis-isomer, the presence of the phenyl group cancels the alternating
t
line width phenomenon observed for the DEPMPO–OOR (R = H, Bu ) spin adducts. The ESR spectra of the DEPMPPOc–OOR
spin adducts exhibit more straightforward patterns and are more easily assignable.
ꢀ
2004 Elsevier Ltd. All rights reserved.
1
. Introduction
two signals. The main signal results from addition of
the superoxide radical on the less hindered face of DEP-
MPO (trans spin adduct, ., Figs. 2 and 3). The cis spin
adduct, formed by addition on the other hindered face
of DEPMPO, corresponds to the minor signal (¤, Figs.
2 and 3). The 12 expected lines of the main signal (trans
spin adduct, .) exhibit an alternating line width effect
and show the resolution of long range c-hydrogen split-
tings from the pyrrolidine ring when low modulation
amplitude is used (Fig. 3). This phenomenon is also ob-
served for the alkylperoxyl adducts of DEPMPO. We
have suggested that hindered rotation around the O–O
peroxyl bond generates this alternating line width since
this phenomenon was observed only in the case of the
ROO (R = H, alkyl) spin adducts. Rotation around
the peroxyl bond induces conformational changes of
the very flexible five-membered ring, thus resulting in
the existence of two quickly exchanging conformers with
significantly different values of the coupling constants.
This alternating line width phenomenon was observed
also with lower intensity for superoxide spin adduct of
The five-membered cyclic nitrones, DMPO 1 (5,5-di-
methyl-1-pyrroline N-oxide) and DEPMPO 2 (5-dieth-
oxyphosphoryl-5-methyl-1-pyrroline
widely used for the detection of free radicals by ESR-
N-oxide)
are
1
spin trapping experiments. Largely as a result of the
angular dependence of the b-proton splitting, these spin
traps provide valuable information on the trapped rad-
ical. Moreover, the additional b-phosphorus coupling
observed for DEPMPO adducts gives further reliability
and confidence in the ESR assignments. The greater sta-
bility of the DEPMPO–OOH adduct compared to that
of the analogue phosphorus-free DMPO–OOH adduct
makes DEPMPO the reagent of choice for superoxide
Å
4
2
detection by ESR-spin trapping. Moreover, peroxyl
radicals are effectively trapped by DEPMPO in water
and the distinction between peroxyl and alkoxyl spin
3
adducts can be achieved unambiguously.
The superoxide DEPMPO spin adduct exhibits a char-
acteristic spectrum composed of a superimposition of
EMPO
3
oxide), DEPPPO 4 (5-diethoxy-phosphoryl-5-phenyl-
(5-ethoxycarbonyl-5-ethyl-1-pyrroline N-
5
6
7
1-pyrroline N-oxide) (Fig. 1) and DMPO 1.
Keywords: Nitrone; DEPMPO; Superoxide; DEPMPPO; Anomeric
effect; Electron spin resonance.
To improve significantly the analysis of ESR spectra
when the signal of either superoxide or alkylperoxyl is
superimposed with the signal of other radicals, a number
*
Corresponding author. Tel.: +33-4-91-288610; fax: +33-4-91-
88758; e-mail: clement@srepir1.univ-mrs.fr
2
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.016

6386
C. Nsanzumuhire et al. / Tetrahedron Letters 45 (2004) 6385–6389
Me
Me
(EtO) (O)P
EtOOC
Me
(EtO) (O)P
2
2
+
H
+
H
+
H
+
H
N
H C
N
N
Ph
N
3
-
-
-
-
O
O
O
O
DMPO (1)
DEPMPO (2)
EMPO (3)
DEPPPO (4)
D
D
Ph
Ph
D
D
(
EtO) (O)P
(EtO) (O)P
(EtO) (O)P
2
2
2
+
+
+
H
H
H
D C
N
Me
N
Me
N
3
-
-
-
O
O
O
DEPMPO d (5)
DEPMPPOc (6)
DEPMPPOt (7)
7
Figure 1. Chemical structures of DMPO and phosphorylated analogues.
~10%
(
EtO) (O)P
2
(EtO) (O)P
2
Hβ
OOH
(EtO) (O)P
OOH
2
.
2
+
+
O
Hβ
N
Me
N
O
Me
N
O
Hβ
Me
.
.
O
-
~
90%
trans spin adduct
cis spin adduct
Figure 2. Trapping of superoxide with DEPMPO.
1
1
acetic anhydride. 1,4-Addition of the nitrophospho-
1
2
nate 10 on 2-phenyl propenal 9 in the presence of a
3
1
catalytic amount of triethylamine in CH CN afforded
3
1
1 as a mixture of two diastereoisomers in equal ratio,
1
4
which was not resolved at this stage. DEPMPPO
was obtained through reductive cyclization by reaction
of 11 with Zn and NH Cl (Scheme 1). The two DEP-
2
mT
4
MPPO diastereoisomers were separated by column
chromatography and further crystallization led to the
pure DEPMPPO cis 6 and trans 7 diastereoisomers.
The stereochemistry of the cis isomer was determined
by X-ray structure analysis (Fig. 4).
Figure 3. High resolution spectrum of DEPMPO–OOH in phosphate
buffer.
1
5
2
of H-labelled DEPMPO analogues were prepared
(
tra of DEPMPO–OOR (R = H, alkyl) adducts were sim-
DEPMPO-d 5, Fig. 1). In this way, the complex spec-
7
2
plified and their signal to noise ratio enhanced by the H
isotopicsubstitution of the c-hydrogens of the pyrrol-
4
idine ring. In earlier studies on stable b-phosphorylated
five-membered ring nitroxides, the presence of a phenyl
Ph
Ph
i
group on the pyrrolidine ring appeared to slow down the
8
O
O
pseudorotation that occurs within the ring. Moreover,
Janzen and co-workers reported that the presence of a
phenyl group in a DMPO spin trap analogue rigidifies
8
9
(
EtO) (O)P
H
Ph
2
ii
9
(
EtO) (O)P
Me
NO
2
the conformation of the corresponding spin adducts.
2
+
Therefore, to limit the internal motions in the spin ad-
ducts, we considered the 5-diethoxy-phosphoryl-5-
methyl-3-phenyl-1-pyrroline N-oxide, a new C(3)-phenyl
analogue of DEPMPO, as an attractive target. We re-
port herein the synthesis of the two diastereoisomers,
the cis and trans 5-diethoxyphosphoryl-3-phenyl iso-
mers, and the ESR study of their use for the spin trap-
ping of various radicals.
H
10
Me
N
Ph
-
O
(EtO)
(O)P
Me
2
DEPMPPOc 6
iii
O
Ph
NO2
(EtO)
(O)P
11
2
+
H
Me
N
-
O
DEPMPPOt 7
2. Synthesis
Scheme 1. Synthesis of the nitrones: (i) Me
2
2 2
NCH NMe , Ac
2
O, 1h,
0
°C, 48%; (ii) Et N, CH CN, 2h, 25°C, 99%; (iii) Zn, NH
2
3
3
4
Cl, THF/
1
0
2-Phenylpropenal 9 was prepared by reaction of phen-
ylacetaldehyde 8 with tetramethyldiaminomethane in
H O, 1h, 0°C, then 6h at 25°C, and chromatography: DEPMPPOt 7,
27% and DEPMPPOc 6, 25%.

C. Nsanzumuhire et al. / Tetrahedron Letters 45 (2004) 6385–6389
6387
Table 1. Simulated hyperfine coupling constants (mT) for DEP-
a
MPPOc 6 spin adducts
Adduct
A
N
A
Hb
A
P
t,b
6
6
6
6
6
6
6
-OBu
1.35
1.27
1.43
1.36
1.46
1.47
1.37
1.85
1.66
2.02
1.81
2.45
2.48
2.11
3.96
3.13
3.87
3.35
3.67
3.63
2.94
t,b
-OOBu
-OH
c
-OOH
2
-CO Na
-CH(CH
3
)OH
-SG
a
b
c
In phosphate buffer at pH7 unless otherwise mentioned.
In benzene.
From XOD/HX system.
Figure 4. X-ray structure of the cis diastereoisomer 6 of DEPMPPO.
1
6
3. ESR studies
change for the computer simulation (Fig. 5b) (see Table
1). Unfortunately, the half-life time of the DEPMPPOc–
OOH adduct was estimated to be only 2min at pH7.0,
t
.1. Superoxide/Bu OO
Å
3
(
data not shown) compared to the ꢀ14min half-life time
When DEPMPPOc 6 was reacted with superoxide, gen-
erated either from xanthin oxidase (XOD)/hypoxanthin
observed for the DEPMPO–OOH under the same experi-
mental conditions.
2
(
HX) or from KO , a spectrum consisting of 12 main
2
lines was observed (Fig. 5a). This latter signal was com-
pletely suppressed in the presence of a high concentra-
tion of superoxide dismutase, while it was replaced by
the DEPMPPOc–OH ESR signal in the presence of glu-
tathion peroxidase and glutathione (GSH) (data not
shown). Thus, the signal in Figure 5a can be attributed
to the DEPMPPOc–OOH spin adduct. Similarly, an
alkylperoxyl adduct of DEPMPPOc was obtained from
Å
3
.2. HO and other radicals
The hydroxyl radical adduct was obtained by reaction of
DEPMPPOc 6 either by incubation with H O and
FeSO or by UV photolysis of H O . The Fenton reac-
4
tion was also carried out in the presence of HCO Na,
2
EtOH or GSH to generate the corresponding CO
2
2
2
2
Å
À
,
2
Å
Å
t
CH(CH )OH and GS radical species. The ESR spec-
3
the photolysis of Bu OOH in degassed toluene. These
spectra are likely to correspond to a trans addition of
trum of the DEPMPPOc–OH adduct consists of 12
lines, compared to the doublet of quadruplet detected
for the DEPMPO–OH adduct. Again in these reactions,
it was assumed that the stereoselective addition occurred
on the less hindered face of DEPMPPOc. The observed
coupling constants are in the range 3.0–4.0mT for phos-
phorus and 1.7–2.5mT for b-hydrogen and they are
characteristic of the added radicals (Table 1).
Å
t
the ROO (R = H, Bu ) species on the face opposite to the
cis related bulky phosphorus and phenyl groups. The
dramaticalternating line width phenomenon, previously
observed for DEPMPO–superoxide (Fig. 3) and
-
tert-butylperoxyl spin adducts, was not detected in the
case of the DEPMPPOc adducts, the signals consist of
2 separated lines with almost the same intensity. There-
fore, the following splittings for DEPMPPOc–OOH
a = 1.36, a = 3.35 and a = 1.81mT) were derived
1
While the values of aHb and a for oxygen- (OH, OR,
P
(
N
P
Hb
OOH and OOR), and sulfur-centred spin adducts of
DEPMPO are in the range 0.8–1.2 and 4.8–5.2mT,
respectively, it is noteworthy that the corresponding
DEPMPPOc adducts exhibit a greater hydrogen cou-
pling and a rather small phosphorus splitting (Table
from calculation without consideration of a chemical ex-
1). These differences traduce significant changes in the
preferred geometries for the two series of spin adducts.
a
3.3. Structure–physical properties correlations
The ESR coupling constants of the DEPMPPOc spin
adducts could be directly dependent on the pyrrolidine
ring geometry and these geometric factors could influ-
ence the relative stabilities of the DEPMPO– and DEP-
MPPOc–superoxide adducts. In the case of DEPMPO–
superoxide adducts, the low value of the hydrogen
b
2
mT
splitting (Æa æ = 1.02mT) indicates a pseudo-equatorial
Hb
position of the H atom and a pseudo-axial position of
b
the C–OOR (R = H, alkyl) group that favours the ano-
Figure 5. ESR signal of DEPMPPOc–superoxide adduct in water. (a)
Signal obtained after 5min incubation of DEPMPPOc (25mM) with
hypoxanthine (0.2mM), xanthine oxidase (0.04U/mL), DTPA
mericintera tc ion between the p system of the nitroxyl
1
7
group and the C–OOR bond. Such a stabilization
was observed by Janzen and co-workers in the case of
the 6,6-dimethyl-1-piperidine N-oxide-superoxide spin
(
0.5mM) in an oxygenated phosphate buffer (0.1M, pH7.4), ( )
ꢁ
unidentified radical species; (b) computer simulation of the experi-
mental spectrum (a).

6388
C. Nsanzumuhire et al. / Tetrahedron Letters 45 (2004) 6385–6389
Karoui, R.; Tuccio, B.; Le Moigne, F.; Culcasi, M.; Pi e´ tri,
S.; Lauricella, R.; Tordo, P. J. Med. Chem. 1995, 38,
58–265; (c) Liu, K.-J.; Miyake, M.; Panz, T.; Swartz, H.
2
M. Free Rad. Biol. Med. 1999, 26, 714–721; (d) Villamena,
F. A.; Zweier, J. L. J. Chem. Soc., Perkin Trans. 2 2002,
1
Free Rad. Biol. Med. 2003, 35, 1149–1157.
340–1344; (e) Keszler, A.; Kalyanaraman, B.; Hogg, N.
4
Figure 6.
T
3
conformation of DEPMPPOc–peroxyl adduct.
3. (a) Karoui, H. Sixth International Symposium on Spin-
Trapping, 08/2000, Marseille, France; (b) Cl e´ ment, J.-L.;
Gilbert, B. C.; Rockenbauer, A.; Tordo, P.; Whitwood, A.
Free Rad. Res. 2002, 36, 883–891; (c) Dikalov, S.; Tordo,
P.; Motten, A.; Mason, R. P. Free Rad. Res. 2003, 37,
1
8
adduct. Moreover, the value of the phosphorus split-
ting (a = 5.03mT) for DEPMPO–OOH indicates a
P
pseudo-axial position of the P(O)(OEt) group in both
2
7
05–712.
conformers (or mean conformers) undergoing the chem-
ical exchange phenomenon. This position leads to a sta-
bilizing hyperconjugative interaction of the C–P bond
with the p system of the nitroxyl group. These two sta-
bilizing interactions may explain in part the stability of
DEPMPO–OOH. On the other hand, in the case of
DEPMPPOc–OOH adduct the two bulky groups (dieth-
oxyphosphoryl and phenyl) adopt both an equatorial
4
. Cl e´ ment, J.-L.; Finet, J.-P.; Fr e´ javille, C.; Tordo, P. Org.
Biomol. Chem. 1 2003, 1591–1597.
5. Olive, G.; Mercier, A.; Le Moigne, F.; Rockenbauer, A.;
Tordo, P. Free Rad. Biol. Med. 2000, 28, 403–408.
6. Karoui, H.; Nsanzumuhire, C.; Le Moigne, F.; Tordo, P.
J. Org. Chem. 1999, 64, 1471–1477.
7
. Fr e´ javille, C.; Karoui, H.; Le Moigne, F.; Culcasi, M.;
Pi e´ tri, S.; Lauricella, R.; Tuccio, B.; Tordo, P. J. Med.
Chem. 1995, 38, 258–265.
position (a = 3.35mT) to minimize the stericintera-c
P
4
tions. This gives rise to a unique preferred T confor-
8. (a) Dembkowski, L.; Finet, J. P.; Frejaville, C.; Le
Moigne, F.; Maurin, R.; Mercier, A.; Pages, P.; Stipa,
P.; Tordo, P. Free Rad. Res. Com. 1993, 19, S23–S32; (b)
Chachaty, C.; Mathieu, C.; Mercier, A.; Tordo, P. Magn.
Res. Chem. 1998, 36, 46–54.
3
mation in which the b-hydrogen adopts an axial
position with a high splitting value (aHb = 1.81mT)
(
Fig. 6). In this case, the anomeric or hyperconjugative
stabilizing interactions cannot take place and therefore,
this nonstabilizing geometry could explain the rapid dis-
appearance of the DEPMPPOc–OOH adduct.
9. Matasyoh, J. C.; Schuler, P.; Stegmann, H. B.; Poyer, J.
L.; West, M.; Janzen, E. G. Magn. Res. Chem. 1996, 34,
3
51–359.
0. Synthesis of 2-phenylpropenal 9. Acetic anhydride
72.5mL, 843mmol) was added dropwise to a mixture of
phenylacetaldehyde (18.0g, 150mmol) and tetra-
1
(
When the radical additions were performed using the
second diastereoisomer (DEPMPPOt, 7) for which the
two faces exhibit both similar steric hindrance, mixtures
of diastereoisomericspin addu ct s were observed, leading
to complex ESR spectra. Therefore this trans-diastereo-
isomer 7 is less interesting for spin trapping experiments.
8
methyldiaminomethane (63mL, 456mmol) at 0°C. After
stirring at room temperature for 1h, ice-cold water
(
150mL) was added and the mixture was extracted with
Et
O (6 · 50mL). The organicphase was distilled under
reduced pressure. The solution of the residue in CH Cl
2
2
2
(
100mL) was washed successively with an aqueous HCl
In conclusion, in the DEPMPPOcis isomer 6, a new
C(3)-phenyl analogue of DEPMPO, the phenyl group
acts as an anchor probe, which blocks the pseudorota-
tion of the pyrrolidine ring and which abolishes the
alternating ESR line width phenomenon, observed with
the DEPMPO superoxide and alkylperoxide adducts.
Thus simpler spectra are obtained for the DEPMPPOc
superoxide and peroxyl radical adducts. However, the
conformational changes induced by the phenyl group
lead to a considerable decrease of the lifetime of the
superoxide spin adduct.
solution (0.05N, 40mL), a saturated NaHCO aqueous
3
solution (30mL) and brine (30mL). The organicphase was
dried over Na SO and concentrated under reduced
2
4
pressure to give 9 (9.6g, 48%) as a colourless liquid used
directly in the next step. dH (200MHz) 6.12 (1H), 6.65
(
C
1H), 7.49–7.21 (5H, m), 9.80 (1H, s); d (50.32MHz)
1
27.89, 128.18, 128.56, 135.54, 135.63, 148.20, 192.94.
1
1. (a) De Solms, S. J. Org. Chem. 1976, 41, 2650–2651; (b)
Takahashi, K.; Shimizu, S.; Ogata, M. Synth. Commun.
1987, 17, 809–815; (c) Vertegen-Haaksma, A. A.; Swarts,
H. J.; Jansen, B. J. M. Tetrahedron 1994, 50, 10095–10106.
12. Zon, J. Synthesis 1984, 661–663.
1
3. Ono, N.; Kamimura, A.; Miyake, H.; Hamamoto, I.; Kaji,
A. J. Org. Chem. 1985, 50, 3692–3698.
1
4. Synthesis of diethyl(2-nitro-5-oxo-4-phenyl-pentan-2-yl)-
phosphonate 11. A solution of Et N (900lL), 2-phenyl-
Acknowledgements
3
propenal 9 (9.6g, 72mmol) and diethyl 1-(1-nitroethyl)-
phosphonate 10 (11.5g, 54.6mmol) in MeCN (50mL) was
stirred for 1.5h and was then concentrated under reduced
pressure to afford the nitrophosphonate 11 as a yellow oil
The authors thank the CNRS for financial support and
Pr. Rockenbauer (Chemical Research Center in Buda-
pest, Hungary) for fruitful discussions.
(
1
18.6g, 97%); d
.30–1.42 (6H, m), 1.63 and 1.73 (3H, d, JH–P 15.0Hz),
2.35–2.77 (1H, m), 3.15–3.52 (2H, m), 3.77 (0.5H, t, J
Hz), 3.87 (0.5H, t, J 6Hz), 4.19–4.26 (4H, m), 7.16–7.40
(5H, m), 9.55 and 9.61 (1H, s); d (75.47MHz) 16.06 and
P H
(40.53MHz) 15.42, 15.17; d (300MHz)
References and notes
6
1
2
. Khan, N.; Wilmot, C. M.; Rosen, G. M.; Demidenko, E.;
Sun, J.; Joseph, J.; OÕHara, J.; Kalyanaraman, B.; Swartz,
H. M. Free Rad. Biol. Med. 2003, 34, 1473–1481.
. (a) Fr e´ javille, C.; Karoui, H.; Tuccio, B.; Le Moigne, F.;
Culcasi, M.; Pi e´ tri, S.; Lauricella, R.; Tordo, P. J. Chem.
Soc., Chem. Commun. 1994, 1793–1794; (b) Frejaville, C.;
C
16.13, 19.46 and 20.47, 34.10 and 34.5, 53.99 (d, JCP
9.0Hz) and 54.18 (d, JCP 7.5Hz), 64.19 (d, JCP 7.5Hz) and
64.36 (d, JCP 6.8Hz), 88.9 (d, JCP 148.7Hz) and 89.0 (d,
JCP 150.2Hz), 128.1, 128.79 and 128.84, 129.13 and
129.23, 134.61 and 135.24, 196.98 and 197.28.

C. Nsanzumuhire et al. / Tetrahedron Letters 45 (2004) 6385–6389
6389
1
5. Synthesis of 5-diethoxyphosphoryl-5-methyl-3-phenyl-1-
pyrroline N-oxide (DEPMPPO): Zn dust (1.57g,
graphic data (excluding structure factors) for compound 6
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication numbers
CCDC 235381.
2
4.0mmol) was added by small portions over 1h to a
solution of the nitrophosphonate 11 (3.3g, 9.62mmol) and
NH Cl (1.28g, 24.0mmol) in THF/H
4
2
O (15/5mL) at 0°C.
16. Hydroxyl radical. Addition of an aqueous solution of
The mixture was stirred for 6h at room temperature. After
filtration and concentration under reduced pressure, water
4 2 2
FeSO (1mM) to the incubation mixture containing H O
(2mM) and DEPMPPOc (25mM) in phosphate buffer
(0.1M, pH7.4) resulted in the observation of DEP-
MPPOc–OH adduct signal. Carbon-centred radicals.
(10mL) was added. The precipitate was filtered, washed
with brine (10mL) and the combined aqueous phases were
extracted with CH Cl (2 · 15mL). The organicphase was
DMSO (10% v/v) was added to the Fenton system to
generate the CH
2
2
Å
dried over Na
2
SO
4
and distilled under reduced pressure.
3
radical, EtOH (10% v/v) to get
Å
Å
The two diastereoisomers of DEPMPPO were isolated
after column chromatography (silica gel, ethyl acetate/
methanol 190/15) and crystallization in ether/pentane.
CH
and NaHSO
3
CH (OH) radical, HCOONa (200mM) for COO
Å
3
3
(50mM) for SO . Superoxide anion radical.
The DEPMPPOc–superoxide adduct was obtained either
by incubation of hypoxanthine (0.2mM), xanthine oxidase
(0.04U/mL), DTPA (0.5mM) and DEPMPPOc (50mM)
in an oxygenated phosphate buffer (07.1M, pH7.4) or by
DEPMPPOtrans isomer 7 (0.8g, 27%); mp 85°C; d
P
(
40.53MHz) 20.45; d
H
(300MHz) 1.38 (6H, t, J 6.0Hz),
.75 (3H, d, JHP 15.0Hz), 1.90–2.0 (1H, m), 3.20–3.40 (1H,
1
m), 4.15–4.45 (5H, m), 7.01 (1H, t, J 3.0Hz), 7.15–7.40
5H, m); d (75.47MHz) 16.4 (d, JCP 5.3Hz), 21.3, 42.0,
4.3, 62.8, 64.2 (d, JCP 6.0Hz), 75.6 (d, JCP 153.5Hz),
27.2, 127.6, 129.0, 137.2 (d, JCP 7.5Hz), 140.5 (d, JCP
.7Hz); (found: C, 55.70; H, 7.22; N, 4.53; calcd for
adding 5% v/v of an equimolar KO /18-crown-6 (0.1M)
2
(
C
DMSO solution to a deoxygenated phosphate buffer
solution of DEPMPPOc (25mM). Bu OO . The DEP-
t
Å
4
1
3
t
MPPOc–OOBu adduct was obtained by UV-photolysis of
a degassed solution of t-BuOOH (1.5M) and DEPMPPOc
(50mM) in benzene. Bu OO . DEPMPPOc–OBu was
obtained by UV-photolysis of a degassed solution of
t
Å
t
C
15
H22NO
4
P: C, 57.87; H, 7.07; N 4.50%).
DEPMPPOcis isomer 6 (0.74g, 25%); mp 65°C; d
P
t
t
(
40.53MHz) 20.23; dH (300MHz) 1.34 (3H, t, J 7.0Hz),
Bu OOBu (0.5M) and DEPMPPOc (50mM) in
toluene.
1
.37 (3H, t, J 7.0Hz), 1.79 (3H, d, JHP 16.0Hz), 2.50–2.80
(
(
6
J
1
2H, m), 4.10–4.45 (5H, m), 6.87–6.88 (1H, m), 7.20–7.45
5H, m); d (75.47MHz) 16.3, 20.8, 40.1, 44.5 (d, JCP
.8Hz), 62.6 (d, JCP 6.8Hz), 63.9 (d, JCP 6.8Hz), 76.1 (d,
CP 163.8Hz), 127.6, 127.9, 129.0, 136.1 (d, JCP 8.3Hz),
40.0; (found: C, 55.60; H, 7.19; N, 4.52; calcd for
17. (a) The anomeric effect and related stereoelectronic effect at
oxygen; Kirby, A. J., Ed.; Springer: Berlin, 1983; (b)
Stereoelectronic effect in organic chemistry; Deslong-
champs, P., Ed.; Pergamon: Oxford, 1983.
18. Zhang, Y.-K.; Janzen, E. G.; Kotake, Y. Magn. Res.
Chem. 1995, 33, S154–S159.
C
C H NO P: C, 57.87; H, 7.07; N 4.50%). Crystallo-
5
1
22
4