New N-substituted dipolarophiles in 1,3-dipolar cycloaddition of nitrones

Article abstract of DOI:10.1055/s-2006-951545

(N-Vinyl)-1,3-oxazolidin-2-ones, -1,3-oxazolidine-2-thiones and -N′-methylimidazolidin-2-one were conveniently used as new dipolarophiles in thermal 1,3-dipolar cycloaddition involving activated nitrones, and led to new 5-N-substituted isoxazolidines in high yields. A moderate to total trans-diastereoselectivity was observed, increasing with the degree of substitution at C-4. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-951545

LETTER
3255
New N-Substituted Dipolarophiles in 1,3-Dipolar Cycloaddition of Nitrones
Dipolarophiles
h
in 1,3-Dipola
a
r
Cycloadd
n
ition of Nitro
h
nes Binh Nguyen,a Catherine Gaulon,a Teddy Chapin,a Sébastien Tardy,b Arnaud Tatibouët,b Patrick Rollin,b
Robert Dhal,a Arnaud Martel,a Gilles Dujardin*a
a
UCO2M UMR 6011 CNRS, Université du Maine, 72085 Le Mans, France
Fax +33(2)43833344; E-mail: gilles.dujardin@univ-lemans.fr
b
ICOA UMR 6005 CNRS, Université d’Orléans, 45067 Orléans, France
Received 24 July 2006
nyl ethers,8 proved to be totally ineffective with 1 at room
temperature and unable to ensure complete conversion in
refluxing chloroform (entry 1). The use of other chelating
Lewis acids in chloroform [SnCl4, Cu(OTf)2, Yb(OTf)3]
Abstract: (N-Vinyl)-1,3-oxazolidin-2-ones, -1,3-oxazolidine-2-thi-
ones and -N¢-methylimidazolidin-2-one were conveniently used as
new dipolarophiles in thermal 1,3-dipolar cycloaddition involving
activated nitrones, and led to new 5-N-substituted isoxazolidines in
high yields. A moderate to total trans-diastereoselectivity was ob- led to disappointing results. Due to the instability of the N-
served, increasing with the degree of substitution at C-4.
acyl-substituted double bond in acidic media, the degrada-
tion of 1 competed with its cycloaddition, particularly at
high temperatures. In contrast, when chelation of 2 with
ZnBr2 in acetone10 was carried out prior to cycloaddi-
tion,11 3 could be obtained with moderate cis-selectivity
and yields (entry 2). Interestingly, TMSOTf significantly
promoted the 1,3-DC at 0 °C in chloroform, giving cy-
cloadduct 3 with a high trans-selectivity but in moderate
yields (entry 3).
Key words: 1,3-dipolar cycloaddition, dipolarophile, nitrone, N-vi-
nyl-oxazolidinone, oxazolidinethione, imidazolidinone
The 1,3-dipolar cycloaddition (1,3-DC) of nitrones with
alkenes, leading to isoxazolidines, is a very important re-
action in organic chemistry.1,2 Numerous uses of isoxazo-
lidines have been reported in total synthesis, often based
on their high ability to be transformed into polyfunctional
amines including g-amino alcohols, b-amino ketones and
esters.3 Inverse electron demand 1,3-DC involving ni-
trones towards electron-rich dipolarophiles have mostly
employed to date vinyl ethers, vinyl esters,4 and N-acyl-
oxazolones,5 thus leading to 5-oxa-substituted isoxazo-
lidines. Reports of 5-aza-substituted isoxazolidines di-
rectly obtained by 1,3-DC have only concerned so far the
synthesis of modified (isoxazolidinyl) nucleosides using
N-vinyl nucleobases as dipolarophiles.6 With the ultimate
aim to develop new aza-substituted dipolarophiles for ste-
reocontrolled access to 5-aza-substituted isoxazolidines,
we have explored in this preliminary work the dipolaro-
philicity of different classes of N-vinyl cyclic amides and
carbamates: N-vinyl-1,3-oxazolidin-2-ones, N-vinyl-1,3-
oxazolidine-2-thiones, N-vinyl-N¢-methylimidazolidin-2-
one, N-vinyl-pyrrolidin-2-one. We describe in this com-
munication our first results related to the thermal 1,3-DC
of these new dipolarophiles with activated nitrones.
Considering the minor improvements obtained with
Lewis acids and in order to achieve a high-yield cycload-
dition while avoiding degradation of 1 and 2, we reconsid-
ered the cycloaddition under thermal conditions. Five
solvents (CHCl3, Me2CO, THF, MeCN, PhMe) with dif-
ferent boiling points were tested under reflux. The trans-
selectivity proved to be solvent-dependent and culminat-
ed at a 4:1 ratio with acetone, chloroform and toluene. The
conversion rate increased with the temperature without
any degradation. Indeed, when the reaction was conduct-
ed in refluxing toluene, complete conversion was
achieved after 24 hours (entry 4). The trans-adduct 3, eas-
ily separated from the cis-isomer, was thus obtained in
72% yield.
COOEt
COOEt
Bn
Bn
N
N
O
EtO2C
Bn
O
O
+
+
N
O
N
N
N
O
O
O
In the first part of our study, the reaction of nitrone 2 with
N-vinyl-1,3-oxazolidine-2-one (1) was investigated under
various Lewis acid catalyzed and thermal conditions
(Scheme 1, Table 1).7 At room temperature and in the ab-
sence of catalyst, no reaction occurred whatever the sol-
vent used. The lack of reactivity of 1 contrasted with the
reactivity of alkyl vinyl ethers under similar conditions.8,9
A limited conversion was observed after 40 hours at re-
flux in chloroform. Catalytic effect of lanthanide salts
such as Eu(fod)3, as reported by Tamura et al. for alkyl vi-
O
O
trans-3
cis-3
2
1
Scheme 1 Reagents and conditions: see Table 1.
In the second part of our study, the reactivity of N-vinyl-
1,3-oxazolidin-2-one (1) was tested towards various ni-
trones (Scheme 2, Table 2) under selected thermal condi-
tions (toluene or p-xylene, reflux).7 Among the nitrones
tested, only 2 and 5 gave good cycloaddition yields. As
expected for an inverse electron demand 1,3-DC reaction,
a dramatic decrease in reactivity was observed with unac-
tivated nitrone 4. Even under harsh conditions (refluxing
SYNLETT 2006, No. 19, pp 3255–3258
0
1
.1
2
.2
0
0
6
Advanced online publication: 23.11.2006
DOI: 10.1055/s-2006-951545; Art ID: G24406ST
© Georg Thieme Verlag Stuttgart · New York

3256
T. B. Nguyen et al.
LETTER
Table 1 Reaction of Nitrone 2 with N-Vinyl-1,3-oxazolidine-2-one (1) under Various Lewis Acid Catalyzed and Thermal Conditions
Entry
Conditions
Conversion (%)a,b Ratio (trans:cis)a Yield (%)c
trans-3
cis-3
13
40
3
1
2
3
4
Eu(fod)3 (0.1 equiv), CHCl3, reflux, 72 h
ZnBr2 (1 equiv), acetone, r.t., 1 h, then reflux, 16 h
TMSOTf (1 equiv), CHCl3, 0 °C, 24 h
70
4:1
54
12
55
72
>60d
>60d
100
1:4
>9:1
4:1
No catalyst, toluene, reflux (113 °C), 24 h
19
a Based on 1H NMR of the crude product.
b Based on residual 2.
c Of pure product after SiO2 chromatography.
d Partial degradation of 2.
R1
R1
R2
p-xylene, 300 h), a limited conversion was observed. In
contrast, the conjugated N-phenyl nitrone 5 displayed a
good reactivity in boiling toluene, leading mainly to the
cis-adduct 8 in high yield. Attempts to activate N-benzyl-
a-phenylnitrone 4 by introducing an electron-withdraw-
ing group (CF3, NO2) in the para-position completely
failed. In those cases, isomerization of nitrones by a 1,3-
prototropic shift (Behrend rearrangement,12 Figure 1) and
degradation of both starting materials led to complex mix-
tures.
R2
N
N
O
R1
O
O
(i) or (ii)
+
+
N
O
N
N
N
O
R2
O
O
O
O
cis-7–9
4–6
trans-7–9
1
Scheme 2 Reagents and conditions: (i) toluene, reflux, 24 h; (ii) p-
xylene, reflux, 6–13 d.
ylimidazolidin-2-one (11) and N-vinylpyrrolidin-2-one
(12, Scheme 3, Table 3).7 In all cases, high global yields,
ranging from 89 to 99%, were obtained. No significant
differences in reactivity and selectivity were observed be-
tween N-vinyl-1,3-oxazolidin-2-ones (1, 13) and their
thio analogues (10, 14). While a 4:1 trans-selectivity was
homogeneously observed with unsubstituted dipolaro-
philes (including enamide 12), trans-selectivity proved
complete when starting from 4,4-dimethyl derivatives. In
both series interestingly, a trans-stereocontrol appears
thus as highly dependent on the substitution patterns of
the dipolarophile, a feature that was not previously ob-
served in vinyl ether series.14 This dependency could be
attributed to the cyclic structure of the dipolarophile, al-
Ph
N
O
Ar
Ph
N
O
Ar
Figure 1
As an alternative to ester 2, other acylated nitrones
(R1 = COPh, CO2H) were tested, albeit without success.
The benzoyl-substituted nitrone proved unstable under
standard conditions, while the carboxylic acid derivative
613 mainly underwent isomerization and degradation.
In the last part of our study, the reaction of nitrone 2 under
optimal thermal conditions (toluene, 110 °C, 24 h) was
extended to N-vinyl-1,3-oxazolidin-2-ones (1, 13), N-vi-
nyl-1,3-oxazolidine-2-thiones (10, 14), N-vinyl-N¢-meth-
Table 2 Reactivity of N-Vinyl-1,3-oxazolidin-2-one (1) towards Various Nitrones
Nitrone/adduct R1
R2
Conditionsa
Yield of 7–9 (%)b
trans:cisc
trans
–
cis
Total
<10c
53
4/7
4/7
5/8
6/9
Ph
Bn
Bn
Ph
Bn
A, 72 h
B, 300 h
A, 144 h
A, 24 h
–
–
Ph
16
<5
–
37
80
–
1:2
1:8
–
Ph
80
CO2H
30d
a A: toluene, reflux; B: p-xylene, reflux.
b Of purified product.
c Based on 1H NMR of the crude product.
d Partial isomerization of the nitrone.
Synlett 2006, No. 19, 3255–3258 © Thieme Stuttgart · New York

LETTER
Dipolarophiles in 1,3-Dipolar Cycloaddition of Nitrones
3257
Table 3 Reaction of Nitrone 2 under Optimal Thermal Conditions with Compounds 1 and 10–14
Enamide/adduct
Yield of 3, 15–19 (%)a
Ratio (trans:cis)b
X
O
S
Y
R
trans
72
cis
19
20
38
19
–
Total
91
1/3
O
H
4:1
10/15
11/16
12/17
13/18
14/19
O
H
73
93
4:1
O
O
O
S
NMe
CH2
O
H
52
91
1.4:1
4:1
H
73
92
Me
Me
89
89
>50:1
>50:1
O
99
–
99
a Of purified product.
b Based on 1H NMR of the crude product.
lowing sterically induced conformational restrictions in able, diastereomeric separation is effective in all cases16
the 1,3-DC transition state. Surprisingly, the trans-selec- and trans-selectivity appears to be tunable by choosing
tivity decreased in the case of N-vinyl-N¢-methylimidazo- appropriate 4-substituents on the cyclic moiety of the di-
lidin-2-one 11.
polarophile. We consider these adducts promising as po-
tential a,b-dipeptide precursors, via cleavage of the N–O
bond, oxidation of the hemiaminal,17 and regeneration of
the b-amino alcohol moiety. Asymmetric extensions of
these reactions are also under progress in our laborato-
ries.17,18
EtO2C
EtO2C
Bn
Bn
N
N
X
EtO2C
O
O
(i)
+
+
N
R
Y
R
R
R
R
N
N
N
X
X
Bn
O
R
Y
Y
Acknowledgment
1, 10–14
trans-3, 15–19
2
cis-3, 15–19
We thank Gwenaelle Lesoif for her contribution.
Scheme 3 Reagents and conditions: (i) toluene, reflux, 24 h.
References and Notes
11%
(1) (a) Nitrile Oxides, Nitrones and Nitronates in Organic
Synthesis, In Organic Nitro Chemistry, Vol. 20; Torssell, K.
B. G., Ed.; VCH: New York, 1988. (b) Frederickson, M.
Tetrahedron 1997, 53, 403.
H3
30%
H4B
H4A
H5
EtOOC
Bn
N
10%
O
(2) Gothelf, K. V.; Jorgensen, K. A. Chem. Rev. 1998, 98, 863.
(3) Synthetic Applications of 1,3-Dipolar Cycloaddition
Chemistry towards Heterocycles and Natural Products;
Padwa, A.; Pearson, W. H., Eds.; John Wiley and Sons:
Hoboken, NJ, 2003.
N
O
S
Figure 2 NOE study of the major trans-adduct 15.
(4) Chiacchio, U.; Corsaro, A.; Gumina, G.; Rescifina, A.;
Iannanazzo, D.; Piperno, A.; Romeo, G.; Romeo, R. J. Org.
Chem. 1999, 64, 9322.
(5) Ishizuka, T.; Matsunaga, H.; Iwashita, J.; Arai, T.; Kunieda,
T. Heterocycles 1994, 37, 715.
(6) (a) Merino, P.; Del Alamo, E. M.; Santiago, F.; Merchan, F.
L.; Simon, A.; Tejero, T. Tetrahedron: Asymmetry 2000, 11,
1543. (b) Chiacchio, U.; Corsaro, A.; Rescifina, A.; Romeo,
G.; Romeo, R. Tetrahedron: Asymmetry 2000, 11, 2045.
(c) Chiacchio, U.; Corsaro, A.; Iannanazzo, D.; Piperno, A.;
Procopio, A.; Rescifina, A.; Romeo, G.; Romeo, R. Eur. J.
Org. Chem. 2001, 1893. (d) Fischer, R.; Druckova, A.;
Fisera, L.; Ribar, A.; Hametner, C.; Cyranski, M. K. Synlett
2002, 1113; and references cited therein.
The relative configuration of all adducts could be eluci-
dated by NOE and NOESY experiments. For instance,
NOE spectra of the major adduct 15 (Figure 2) established
a trans relationship, deduced from the spatial proximity of
H5 with H4A, and of H4B with H3. NOESY experiments
confirmed the spatial proximity between H3 and H5 in the
sole cis-adduct.
In summary, we have demonstrated in this preliminary
work the ability of N-vinyl-1,3-oxazolidin-2-ones, 2-thio
analogues, N-vinyl-N¢-methylimidazolidin-2-one, N-vi-
nylpyrrolidin-2-one to act as original dipolarophiles15 in
inverse electron demand 1,3-DC reactions with activated
nitrones such as 2. Those dipolar cycloadditions proceed
optimally in refluxing toluene, giving excellent yields
within a day. This thermal procedure is especially remark-
able by its simplicity. Although trans-selectivity is vari-
(7) Optimized Experimental Procedure for Thermal 1,3-
DC.
A stirred toluene solution (5 mL) of dipolarophile (0.5
mmol, 1 equiv) and nitrone (0.5 mmol, 1 equiv) was refluxed
under argon. After cooling, the crude mixture was
concentrated in vacuo. The product was purified by column
Synlett 2006, No. 19, 3255–3258 © Thieme Stuttgart · New York

3258
T. B. Nguyen et al.
LETTER
chromatography on silica gel.
Physical data of selected isolated adducts.
135.9 (C–Ar), 169.1 (C=O), 187.6 (C-2¢). HRMS (ESI+):
m/z calcd for C16H20N2O4SK [M + K]+: 375.0781; found:
375.0775.
Compound cis-3: pale yellow oil. IR (neat): 1738, 1194,
1028 cm–1. 1H NMR (400 MHz, CDCl3): d = 1.25 (t, 3 H,
J = 7.1 Hz, Et), 2.57 (ddd, 1 H, J = 4.1, 7.6, 13.6 Hz, H-4A),
2.87 (ddd, 1 H, J = 8.2, 9.1, 13.6 Hz, H-4B), 3.55 (dd, 1 H,
J = 7.6, 9.1 Hz, H-4¢), 3.75 (dt, 1 H, J4 = 5.9, 9.1 Hz, H-4¢),
3.84 (q, 1 H, J = 9.1 Hz), 4.00 (dd, 1 H, J = 13.5 Hz), 4.12
(m, 3 H), 4.29 (m, 2 H, H-5¢), 5.92 (dd, 1 H, 3J5-4A = 4.1 Hz,
3J5-4B = 8.2 Hz, H-5), 7.28–7.37 (m, 5 H, H–Ar). 13C NMR
(100 MHz, CDCl3): d = 13.9 (Et), 36.3 (C-4), 40.8 (C-4¢),
61.5, 61.6 (Bn, OEt), 62.3 (C-5¢), 66.6 (C-3), 81.5 (C-5),
127.6, 128.2, 129.1, 135.8 (C–Ar), 157.6 (C-2¢), 169.8
(C=O).
Compound trans-19: pale yellow oil. IR (neat): 1734, 1474,
1353, 1283, 1208 cm–1. 1H NMR (400 MHz, CDCl2CDCl2,
60 °C): d = 1.20 (t, 3 H, 3J7-8 = 7.1 Hz, Et), 1.22 (s, 3 H, Me),
1.30 (s, 3 H, Me), 2.80 (ddd, 1 H, 3J4A-5 = 6.0 Hz, 3J4A-3 = 8.6
Hz, 2J4A-4B = 13.9 Hz, H-4A), 3.08 (ddd, 1 H, 3J4B-3 = 6.3 Hz,
3J4B-5 = 7.6 Hz, 2J4B-4A = 13.9 Hz, H-4B), 3.97 (dd, 1 H,
3J3-4A = 8.6 Hz, 3J3-4B = 6.3 Hz, H-3), 4.01 (s, 2 H, Bn), 4.06–
4.12 (m, 4 H, OEt and H-5¢), 5.74 (dd, 1 H, 3J5-4A = 6.0 Hz,
3J5-4B = 7.6 Hz, H-5), 7.16–7.29 (m, 5 H, H–Ar). 13C NMR
(100 MHz, CDCl2CDCl2, 60 °C): d = 14.2 (Et), 25.4 (Me),
25.8 (Me), 37.1 (C-4), 60.4 (Bn), 61.3 (OEt), 64.2 (C-4¢),
66.0 (C-3), 79.3 (C-5¢), 84.6 (C-5), 127.5, 128.2, 129.5,
136.4 (C–Ar), 169.6 (C=O), 186.4 (C-2¢).
Compound trans-3: pale yellow oil. IR (neat): 1737, 1182,
1034 cm–1. 1H NMR (400 MHz, CDCl3): d = 1.28 (t, 3 H,
3J8-7 = 7.1 Hz, Et), 2.55 (ddd, 1 H, 3J4A-5 = 4.4 Hz, 3J4A-3 = 7.9
Hz, 2J4A-4B = 13.3 Hz, H-4A), 2.83 (ddd, 1 H, 3J4B-5 = 6.9 Hz,
(8) Tamura, O.; Mita, N.; Gotanda, K.; Yamada, K.; Nakano, T.;
Katagiri, R.; Sakamoto, M. Heterocycles 1997, 46, 95.
(9) (a) Jensen, K. B.; Hazell, R. G.; Jørgensen, K. A. J. Org.
Chem. 1999, 64, 2353. (b) Simonsen, K. B.; Bayon, P.;
Hazell, R. G.; Gothelf, K. V.; Jørgensen, K. A. J. Am. Chem.
Soc. 1999, 121, 3845.
3J4B-3 = 7.9 Hz, 2J4B-4A = 13.3 Hz, H-4B), 3.54 (t, 2 H, 3J4¢-5¢
=
7.9 Hz, H4¢), 3.74 (m, 1 H, H-3), 4.11 (m, 2 H, Bn), 4.18 (q,
2 H, 3J7-8 = 7.1 Hz, OEt), 4.30 (t, 2 H, 3J4¢-5¢ = 7.3 Hz, H5¢),
5.84 (dd, 1 H, 3J5-4A = 4.4 Hz, 3J5-4B = 7.9 Hz, H-5), 7.27–
7.38 (m, 5 H, H–Ar). 13C NMR (100 MHz, CDCl3): d = 14.1
(Et), 35.4 (C-4), 40.4 (C-4¢), 60.3 (Bn), 61.5 (OEt), 62.1 (C-
5¢), 65.3 (C-3), 82.1 (C-5), 127.7, 128.3, 129.3, 135.8 (C–
Ar), 157.2 (C-2¢), 169.3 (C=O). HRMS (EI): m/z calcd for
C16H20N2O5 [M]+: 320.1372; found: 320.1393.
(10) Merino, P.; Anoro, S.; Cerrada, E.; Laguna, M.; Moreno, A.;
Tejero, T. Molecules 2001, 6, 208.
(11) Complete complexation was ascertained by 1H NMR.
(12) The rearranged nitrone was identified by the low-field signal
of the ortho aromatic protons in 1H NMR. For seminal work
on the Behrend rearrangement and further studies, see:
(a) Behrend, R.; Konig, E. Justus Liebigs Ann. Chem. 1891,
238. (b) Behrend, R.; Konig, E. Justus Liebigs Ann. Chem.
1891, 355. (c) Smith, P. A. S.; Gloyer, S. E. J. Org. Chem.
1975, 40, 2504.
Compound cis-8: colorless crystals; mp 185–186 °C. IR
(neat): 1743, 1410, 1234, 1018 cm–1. 1H NMR (400 MHz,
CDCl3): d = 2.40 (ddd, 1 H, 3J4A-5 = 5.3 Hz, 3J4A-3 = 6.3 Hz,
2J4A-4B = 13.4 Hz, H-4A), 3.04 (dt, 1 H, 3J4B-3 = 3J4B-5 = 8.3
Hz, 2J4B-4A = 13.4 Hz, H-4B), 3.37 (dt, 1 H, 3J4¢B-5¢A = 5.3 Hz,
2J4¢B-4¢A = 3J4¢B-5¢B = 8.3 Hz, H-4¢B), 3.68 (q, 1 H, 3J4¢A-5¢
=
(13) Tokunaga, Y.; Ihara, M.; Fukumoto, K. Tetrahedron Lett.
1996, 37, 6157.
(14) Under our standard conditions, similar levels of trans-
selectivity were observed in the reaction of 1 with ethyl vinyl
ether (4:1) and tert-butyl vinyl ether (3:1).
(15) For preparation of dipolarophiles, see: (a) Gaulon, C.;
Gizecki, P.; Dhal, R.; Dujardin, G. Synlett 2002, 952.
(b) Gaulon, C.; Dhal, R.; Dujardin, G. Synthesis 2003, 2269.
(c) Chery, F.; Desroses, M.; Tatibouët, A.; De Lucchi, O.;
Rollin, P. Tetrahedron 2003, 59, 4563. (d) Girniene, J.;
Tardy, S.; Tatibouët, A.; Sackus, A.; Rollin, P. Tetrahedron
Lett. 2004, 45, 6443.
(16) Such diastereomeric separation was seldom reported for
adducts deriving from alkyl vinyl ethers. For a successful
case, see: Fischer, R.; Dugovi, B.; Wiesenganger, T.; Fisera,
L.; Hametner, C.; Prónayová, N. Heterocycles 2005, 65,
591.
(17) For previous use of chiral N-vinyl-1,3-oxazolidin-2-ones in
[4+2] asymmetric reactions, see: Gaulon, C.; Dhal, R.;
Chapin, T.; Maisonneuve, V.; Dujardin, G. J. Org. Chem.
2004, 69, 952.
(18) For recent use of chiral N-vinyl-1,3-oxazolidine-2-thiones in
[4+2] asymmetric reactions, see: Tardy, S.; Tatibouët, A.;
Rollin, P.; Dujardin, G. Synlett 2006, 1425.
2J4¢A-4¢B = 8.3 Hz, H-4¢A), 4.26 (dt, 1 H, 3J5¢B-4¢ = 8.3 Hz,
2J5¢B-5¢A = 9.1 Hz, H-5¢B), 4.34 (ddd, 1 H, 3J5¢A-4¢B = 5.3 Hz,
3J5¢A-4¢A = 8.3 Hz, 2J5¢A-5¢B = 9.1 Hz, H-5¢A), 4.72 (dd, 1 H,
3J3-4A = 6.3 Hz, 3J3-4B = 8.3 Hz, H-3), 6.13 (dd, 1 H, 3J5-4A
5.3 Hz, 3J5-4B = 8.3 Hz, H-5), 7.00 (t, 1 H, J = 7.5 Hz), 7.03
(d, 2 H, J = 7.5 Hz,), 7.24 (t, 2 H, J = 7.5 Hz,), 7.31 (t, 1 H,
J = 7.5 Hz), 7.39 (t, 1 H, J = 7.5 Hz), 7.51 (d, 1 H, J = 7.5
Hz,). 13C NMR (100 MHz, CDCl3): d = 40.2 (C-4¢), 41.2
(C-4), 62.3 (C-5¢), 70.0 (C-3), 82.4 (C-5), 116.3, 123.2,
126.4, 127.8, 128.9, 129.0, 140.6, 150.2 (C–Ar), 157.8
(C-2¢). Anal. Calcd for C18H18N2O3: C, 69.66; H, 5.85; N,
9.03. Found: C, 69.64; H, 5.74; N, 9.18.
=
Compound trans-15: pale yellow oil. IR (neat): 1731, 1489,
1477, 1324, 1260, 1186 cm–1. 1H NMR (400 MHz, CDCl3):
d = 1.32 (t, 3 H, 3J8-7 = 7.1 Hz, Et), 2.45 (ddd, 1 H, 3J4A-
5 = 3.5 Hz, 3J4A-3 = 8.1 Hz, 2J4A-4B = 13.9 Hz, H-4A), 3.02
(ddd, 1 H, 3J4B-5 = 8.1 Hz, 3J4B-3 = 9.1 Hz, 2J4B-4A = 13.9 Hz,
H-4B), 3.59–3.71 (m, 2 H, H-4¢), 3.84 (br, 1 H, H3), 4.12 (s,
2 H, Bn), 4.23 (q, 2 H, 3J7-8 = 7.1 Hz, OEt), 4.41–4.51 (m, 2
H, H-5¢), 6.39 (dd, 1 H, 3J5-4A = 3.5 Hz, 3J5-4B = 8.1 Hz, H-5),
7.28–7.35 (m, 5 H, H–Ar). 13C NMR (100 MHz, CDCl3):
d = 14.3 (Et), 36.7 (C-4), 43.4 (C-4¢), 59.2 (Bn), 61.5 (OEt),
64.8 (C-3), 67.0 (C-5¢), 84.7 (C-5), 127.8, 128.4, 129.3,
Synlett 2006, No. 19, 3255–3258 © Thieme Stuttgart · New York