An efficient synthesis of 3-alkyl-2-alkyliminooxazolidin-4-one via a domino reaction

Article abstract of DOI:10.1002/cjoc.201190082

3-Alkyl-2-alkyliminooxazolidin-4-ones were prepared from a copper-catalyzed domino intermolecular nucleophilic addition of α-hydroxy-(or mecapto) carboxylic acid ester to carbodiimide and a followed nucleophilic substitution of the formed amino group to c

Full text of DOI:10.1002/cjoc.201190082

FULL PAPER
An Efficient Synthesis of 3-Alkyl-2-alkyliminooxazolidin-4-one
via a Domino Reaction
,
Liu, Yongweia(刘永伟)
Li, Zhengning a,b(李争宁)
Jiang, Lana(姜岚)
*
Zheng, Aijuna(郑爱军)
a College of Environmental and Chemical Engineering, Dalian University, Dalian, Liaoning 116622, China
b Liaoning Key Laboratory of Bioorganic Chemistry, Dalian University, Dalian, Liaoning 116622, China
3-Alkyl-2-alkyliminooxazolidin-4-ones were prepared from a copper-catalyzed domino intermolecular nucleo-
philic addition of α-hydroxy-(or mecapto) carboxylic acid ester to carbodiimide and a followed nucleophilic substi-
tution of the formed amino group to carboxylic acid ester. The reactions could be performed under convenient con-
ditions and good yields were achieved in most cases.
Keywords iminooxazolidin-4-one, synthesis, carbodiimide, α-hydroxycarboxylate
Introduction
methyl-carbodiimide, N,N'-di-iso-propylcarbodiimide
(DIC)], and concluded that 3-alkyl-2-alkyliminooxa-
zolidin-4-one and O-alkyl isourea were yielded.7a Rapi
et al.9 obtained 2-methylimino-3-methyloxazolidin-4-
ones from the active dimethylcarbodiimide and α-hy-
droxy acid esters. Hydrolysis of 3-alkyl-2-alkylimino-
oxazolidin-4-one gave 2-amino-4-oxazolinone,10 which
is of medicinal interest.11-13 Noguchi et al.14 reported
that α-hydroxycarboxylic acid reacted with CDI afford-
ing 2-amino-4-oxazolinone, which could not be formed
from the corresponding α-hydroxycarboxylic acid ester.
Brady prepared 3-iso-propyl-2-iso-propylimino-4-azo-
lidinone via the reaction of DIC with chloroacetyl chlo-
ride.10 In regarding the concise and clean synthesis of
substituted 2-iminooxazolidin-4-one from N,N'-di-iso-
propylcarbodiimide and alkyl α-hydroxycarboxylate,
herein we wish to report our results for this reaction,
including structural characterization and yields.
Carbodiimide (CDI) has been extensively used as
dehydrating reagent in the formation of amide and es-
ters.1 In the latter case, two mechanisms, with O-alkyl
isourea or O-acyl isourea as the intermediate, may be
involved, depending on the sequence of addition of re-
agents and the reaction conditions. A one pot reaction
manner among acids, alcohols and CDI is adapted in
most cases where O-acyl isourea is the intermediate. On
the other hand, formation of O-alkyl isourea prior to the
addition of acid offers some advantages, including mild
reaction condition, inversion of the configuration of
secondary alcohols, clean reaction and excellent yields.2
Recent development of this method results in the use of
polymer-supported CDI and synthesis of high purity
ester in short reaction time and easy separation using
solid-phase synthesis and microwave heating.3 Re-
placement of acid with phenol, ether is formed. Al-
though CDI has been extensively used in organic reac-
tions, the exploration of new reaction is still in pro-
gress.4,5 We have found that O-alkyl isourea, derived
from CDI and alcohol, can be converted into alkyl hal-
ide in the presence of acyl halide or N-halo-succini-
mide.6 In a program toward the synthesis of phenyl ether,
we tried to adapt a literature method using O-alkyl
isourea and phenol. However, when α-hydroxycarbox-
ylic acid ester was used as the alcohol component, in-
stead of the expected isourea, substituted 2-alkylimi-
nooxazolidin-4-one was formed. A search of literature
shows that there were a few examples of this kind of
reaction reported in 1960s.7,8 Mainly based on elemental
analysis, Schmidt has reported that alkyl α-hydroxy-
acetate reacted with 2 equivalent of CDI [N-t-butyl-N'-
Resuts and discussion
When a mixture of DIC, ethyl lactate and catalytic
amount of CuCl was stirred at room temperature, TLC
indicated that a new compound with lower polarity than
lactate was formed. Separation and spectral analysis
indicated its structure as 3-iso-propyl-2-iso-propyl-
imino-5-methyl-oxazolidin-4-one. In IR, the disappear-
ance of absorption at 1740 cm－ 1 and the appearance of a
strong absorption at 1691 cm－ indicated that the ester
1
group in lactate was converted to another carbonyl
group. MS and HRMS gave the molecule as
1
C10H19N2O2. H NMR and 13C NMR supported the
structure as substituted 2-imino-oxazolidin-4-one. Then,
efforts towards increasing the yield are devoted, and a
*
E-mail: znli@dl.cn
Received August 3, 2010; revised September 30, 2010; accepted October 23, 2010.
Project supported by the National Natural Science Foundation of China (No. 20672016).
Chin. J. Chem. 2011, 29, 303— 308
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
303

Liu et al.
FULL PAPER
scan of different Lewis acids including CuCl, FeCl3,
FeCl2, CoCl2, ZnCl2 and BF3•Et2O showed that the
copper salt gave the cleanest reaction product as moni-
tored by GC, whereas in the presence of other metal
salts, prominent amount of dimmer of DIC was formed.
Accordingly, CuCl, one of the cheapest copper salts,
was employed as the catalyst. In the presence of 3.5
mol% of CuCl, the domino reaction could be achieved
in 10 h, affording the product as the single spot in TLC,
and 3a in 82.3% isolated yield. The high yield indicated
the preference reaction between α-hydroxycarboxylate
and CDI even though ethanol was formed in the process.
The result may be reasoned as a nucleophilic addition of
α-hydroxycarboxylic acid ester to CDI, which yields a
normal isourea, followed by a nucleophilic addition of
the amino group in the isourea intermediate to carbox-
ylic acid ester and an elimination, which affords an am-
ide, as shown in Scheme 1. Replacing lactate with ethyl
interest.
It should be noted that an OH or SH group attached
to α-C of carboxylate is crucial for this cyclization. In
literature, reaction between β-hydroxycarboxylate and
CDI gave α,β-unsaturated carboxylate1a,16 along with
dialkylurea. Therefore, it is not surprising when 1,3-di-
iso-propyl-thiourea, a dehydrosulfuration product, was
formed from methyl 3-mercaptopropionate and DIC in
the presence of CuCl. Methyl salicylate failed to yield a
6-membered cyclization product, even though ben-
zoxazine derivatives were formed from salicylic acid
and CDI.17
In summary, we have reported a convenient method
for the synthesis of 3-alkyl-2-alkyliminooxazolidin-4-
ones and its sulfur analogues from α-hydroxy-(or mer-
capto) carboxylic acid ester and carbodiimide.
Experimental
mandelate,
3-iso-propyl-2-iso-propylimino-5-phenyl-
Infrared spectra were recorded on a Nicolet 5－50
oxazolidin-4-one was formed. However, the reaction
was slower than its lactate analogue. 39% and 70.9%
yields were obtained in 4 and 24 h, respectively.
Cu(OTf)2 exhibited higher reactivity than CuCl. 89.4%
yield was furnished in 11.5 h at room temperature. The
reaction time could be shortened by increasing the reac-
tion temperature. Thus, an 87.4% yield was achieved in
4.5 h at 50 ℃ with CuCl as the catalyst. Methyl
2-hydroxy-2-methyl-propionate, in which hydroxyl
group attached to a tertiary carbon, also reacted with
DIC and DCC, and gave the cyclized product. But the
reaction of DCC is sluggish. Reaction at 50 ℃ for 12 h
and 60 ℃ for 7 h gave the product in 54.0% yield. Re-
action of methyl 2-mercaptopropionate, faster than the
lactate analogue, gave the thiazolidin-4-one. Previously,
the thiazolidin-4-one was prepared from mercapto-
propionic acid and carbodiimide.15
1
FT-IR spectrometer in nujol from 4000 to 400 cm .
Specific rotation was recorded at 25 ℃ on a Kruss
P3002RS Digital Polarimeter. NMR spectra were re-
corded in CDCl3 on a Bruker DRX500 spectrometer
operating at 500 and 125 MHz for H NMR and 13C
1
NMR, respectively. All data were calibrated at δ 7.26 or
δ 0.00 for H NMR (residual CHCl3 or TMS, respec-
1
tively), and δ 77.1 or δ 0.0 for 13C NMR from the origi-
nal spectra. Spectral features are designated as: hept＝
heptlet, m＝multiplet, t＝triplet, d＝doublet and s＝
singlet. Low resolution mass spectra (LRMS) were re-
corded on an HP 6890/5973 GC-MS mass spectrometer
at 70 eV; high resolution mass spectra (HRMS) were
recorded on a Micromass GTC Gas Chromatogra-
phy/TOF Mass Spectrometer or UPLC/Q TOF Mass
Spectrometer, and spectr＋al data were obtained for the
molecular ion or [M＋H] , respectively.
Scheme 1 Formation of 3a from DIC and ethyl lactate
Typical procedure for the synthesis of 3-iso-propyl-
2-iso-propylimino-5-methyl-oxazolidin-4-one
Under an argon atmosphere, a mixture of DIC (0.263
g, 2.08 mmol), ethyl lactate (0.249 g, 2.10 mmol) and
CuCl (0.007 g, 0.07 mmol) was stirred at room tem-
perature. When most of lactate was consumed, as indi-
cated by TLC and GC, the mixture was separated by
column chromatography, yielding 5-methyl-3-iso-pro-
pyl-2-iso-propylimino-oxazolidin-4-one (3a) as the
lowest polar compound. 3a: liquid, Rf＝0.39 [V(EA)/
V(PE)＝5/95]. (S)-isomer, 3a': [α]2D5 10.1 (c 1.83,
1
CH2Cl2); H NMR (CDCl3, 500 MHz) δ: 4.584 (q, J＝
6.85 Hz, 1H), 4.329 (hept, J＝6.90 Hz, 1H), 3.857 (hept,
J＝6.35 Hz, 1H), 1.477 (d, J＝6.85 Hz, 3H), 1.414 (d,
J＝6.95 Hz,, 3H), 1.406 (d, J＝6.35 Hz, 1H), 1.100 (d,
J＝6.30 Hz, 6H); 13C NMR (CDCl3, 125 MHz) δ:
173.08, 146.15, 74.68, 45.82, 45.09, 24.28, 24.19, 18.88
The substrates were then extended to diethyl tartrate.
Both DIC and DCC can give good yield of (3-alkyl-2-
alkylimino-4-oxo-oxazolidin-5-yl)-2-hydroxyacetic acid
ethyl ester when 1 or 2 equivalents of DIC or DCC were
used at room temperature. With more CDI and higher
temperature, complex mixture of products was observed,
and they were not further isolated due to lower synthetic
－1
(2C), 17.24; IR v: 1691, 1469 cm ; MS m/z (%): 198
([M]＋, 42), 183 (44), 157 (40), 151 (100), 127 (45), 115
304
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Synthesis of 3-Alkyl-2-alkyliminooxazolidin-4-one via a Domino Reaction
Table 1 Synthesis of substituted 3-alkyl-2-alkyliminooxazolidin-4-one
Entry
DIC/equiv.
Cat.a/mol%
Temp./Time (h)
r.t./1.5
Product
Yieldb/%
43.1
1
2
3
1.0
1.0
1.0
3.5
3.5
3.5
r.t./10
3a
82.3
r.t./6
80.2
4
1.0
3.5
r.t./4
39.0
5
6
7
1.0
1.0
1.6
3.5
3.5
r.t./24
50 ℃/4.5
r.t./11.5
3b
3b
3b
70.9
87.4
89.4
3.5/Cu(OTf)2
8
1.0
3.5
3.5
r.t./48
63.4
9
1.2
50 ℃/5.5
42.9
10
11
1.2
1.1
4.0
5.0
r.t./28
r.t./24
3d
71.2
65.6
12
13
14
1.1
1.1
1.1
5.0
5.0
5.0
r.t./15; 50 ℃/4
50 ℃/12; 61 ℃/7
r.t./5
20.0
54.0
85.8
3f
Chin. J. Chem. 2011, 29, 303— 308
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
305

Liu et al.
FULL PAPER
Continued
Entry
DIC/equiv.
1.5
Cat.a/mol%
5.0
Temp./Time (h)
Product
Yieldb/%
15
16
r.t./20; 50 ℃/17
33.1
85.6
1.1
1.0
5.0
5.0
r.t./10
r.t./10
17
18
74.4
62.9
1.1
5.0
r.t./12
a Unless otherwise indicated, CuCl was used. b Isolated yield after chromatography.
(22), 84 (21), 69 (54), 55 (12), 43＋(21), 27 (6). HRMS
calcd for C10H19N2O2 ([M＋H] ) 199.1441, found
199.1450.
C16H27 N2O2 ([M＋H]＋) 279.2067, found 279.2076.
3d: liquid, Rf＝0.58 [V(EA)/V(PE)＝10/90]. [α]D25
－2.2 (c 0.325, CH2Cl2); 1H NMR (CDCl3, 500 MHz) δ:
7.420—7.340 (m, 5H), 5.426 (s, 1H), 3.997—3.965 (m,
1H), 3.668—3.631 (m, 1H), 2.341—2.221 (m, 2H),
1.809—1.573 (m, 10H), 1.426—1.172 (m, 8H); 13C
NMR (CDCl3, 125 MHz) δ: 170.77, 145.85, 134.46,
129.19, 128.91, 126.10, 79.08, 53.69, 53.15, 34.39,
34.32, 28.51, 28.38, 25.93,－25.83, 25.80, 25.15, 24.7＋1,
3b: colorless solid, m.p. 51—52 ℃; Rf ＝0.44
[V(EA)/V(PE)＝10/90]. (S)-Isomer, [α]2D5 1.6 (c 0.68,
1
CH2Cl2); H NMR (CDCl3, 500 MHz) δ: 7.428—7.344
(m, 5H), 5.440 (s, 1H), 4.390 (hept, J＝6.90 Hz, 1H),
3.994 (hept, J＝6.30 Hz, 1H), 1.447 (d, J＝6.95 Hz,
3H), 1.4109 (d, J＝6.95 Hz, 3H), 1.167 (d, J＝6.30 Hz,
13
1
3H), 1.158 (d, J＝6.30 Hz, 3H); C NMR (CDCl3, 125
24.67; IR v: 1710, 1468 cm ; MS m/z (%): 340 ([M] ,
MHz) δ: 170.68, 146.02, 134.29, 129.23, 128.94, 126.00,
79.12, 46.07, 45.56, 24.35, 24.34, 18.99, 18.88; IR v:
2), 260 (55), 259 (100), 215 (7), 177 (33), 160 (7), 144
(7), 132 (17), 118 (26), 106 (18), 90 (16), 67 (7), 55 (19),
41 (12), 29 (2). HRMS calcd for C21H29N2O2 ([M＋
H]＋) 341.2224, found 341.2229.
＋
－1
1716, 1468, 1428 cm ; MS m/z (%): 260 ([M] , 44),
245 (95), 218 (36), 203 (51), 189 (4), 175 (85), 160 (12),
146 (12), 132(100), 118 (79), 105 (22), 96 (11), 84 (32),
69 (24), 58 (8), 43 (11), 27 (3). HRMS calcd for
C15H21N2O2 ([M＋H]＋) 261.1598, found 261.1615.
3c: colorless solid, m.p. 68—70 ℃ (racemic); Rf＝
0.39 [V(EA)/V(PE)＝5/95]. 1H NMR (CDCl3, 500 MHz)
δ: 4.574 (q, J＝6.9 Hz, 1H), 3.925 (tt, J＝18.4, 3.9 Hz,
1H), 3.514 (tt, J＝9.3, 4.0 Hz, 1H), 2.238 (dddd, J＝
12.4, 9.6, 5.4, 3.8 Hz, 2H), 1.805 (d, J＝13.3 Hz, 2H),
1.746—1.561 (m, 8H), 1.470 (d, J＝6.9 Hz, 3H),
3e: colorless solid, m.p. 59—61 ℃; Rf ＝0.41
1
[V(EA)/V(PE)＝5/95]. H NMR (CDCl3, 500 MHz) δ:
4.305 (hept, J＝6.9 Hz, 1H), 3.829 (hept, J＝6.3 Hz,,
1H), 1.450 (s, 6H), 1.403 (d, J＝6.9 Hz, 6H), 1.095 (d,
J＝6.3 Hz, 6H); 13C NMR (CDCl3, 125 MHz) δ: 175.37,
145.49, 81.12, 45.75, 44.94, 24.19 (2C), 23.88 (2C),
－1
18.85 (2C); IR v: 1710, 1475 cm ; MS m/z (%): 212
([M]＋, 77), 197 (82), 184 (3), 169 (34), 155 (100), 143
(11), 127 (79), 112 (40), 98 (12), 84 (81), 69 (91), 70
(58), 58 (58), 41 (67), 27(14). HRMS calcd for
C11H20N2O2 ([M]＋) 212.1519, found 212.1518.
13
1.364—1.312 (m, 8H); C NMR (CDCl3, 125 MHz) δ:
173.20, 145.99, 74.60, 53.53, 52.74, 34.34, 34.23, 28.42,
25.－95 (2C), 25.82, 25.16, 24.70, 17.34; IR v: 1703, 1454
3f: colorless solid, m.p. 68—69 ℃; Rf ＝0.40
＋
1
1
cm ; MS m/z (%): 278 ([M] , 3), 198 (61), 197 (100),
167 (10), 153 (40), 141 (29), 115 (83), 98 (15), 81 (34),
67 (17), 55 (48), 41 (29), 28 (6). HRMS calcd for
[V(EA)/V(PE)＝5/95]. H NMR (CDCl3, 500 MHz) δ:
3.907 (tt, J＝18.4, 4.4 Hz, 1H), 3.486 (tt, J＝9.3, 4.0 Hz,
1H), 2.234 (tdd, J＝16.1, 12.5, 3.4 Hz, 2H), 1.800 (d,
306
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Chin. J. Chem. 2011, 29, 303— 308

Synthesis of 3-Alkyl-2-alkyliminooxazolidin-4-one via a Domino Reaction
J＝13.5 Hz, 2H), 1.744—1.679 (m, 4H), 1.671—1.622
(m, 3H), 1.589—1.558 (m, 1H), 1.441 (s, 6H), 1.368—
J＝9.65 Hz, 1H), 1.356—1.152 (m, 11H); 13C NMR
(CDCl3, 125 MHz) δ: 170.91, 169.21, 145.63, 78.19,
69.70, 62.79, 53.55, 53.31, 34.21, 33.91, 28.48, 28.23,
25.88, 25.79, 25.75, 25.13,－24.56, 24.53, 14.09; IR v:
13
1.148 (m, 8H); C NMR (CDCl3, 125 MHz) δ: 175.54,
145.34, 81.03, 53.46, 52.61, 34.28 (2C), 28.41 (2C),
25.98, 25.82 (2C), 25.18, 24.74 (2C), 24.00; IR v: 1710,
1468, 1407, 1381, 1280, 1219, 1072, 1025, 1092, 964,
＋
1
3382, 1763, 1690, 1454 cm . MS m/z (%): 366 ([M] ,
1), 286 (43), 285 (100), 267 (3), 241 (4), 203 (27), 185
(12), 143 (5), 129 (10), 114 (4), 98 (7), 81 (10), 67 (5),
55 (16), 41 (9), 29 (5). HRMS calcd for C19H30N2O5
([M]＋) 366.2149, found 366.2167.
＋
－1
890, 756, 696 cm ; MS m/z (%): 292 ([M] , 5), 249 (5),
212 (57), 211 (100), 167 (29), 155 (9), 141 (5), 129 (56),
110 (6), 98 (17), 86 (25), 69 (22), 55 (22), 41 (24), 29
(3). HRMS calcd for C17H28N2O2 ([M]＋) 292.2145,
found 292.2148.
3k: liquid, Rf ＝0.54 [V(EA)/V(PE)＝1/4]. [α]D25
1
－0.124 (c 2.42, CH2Cl2); H NMR (CDCl3, 500 MHz)
1
3g: liquid, Rf＝0.45 [V(EA)/V(PE)＝5/95]. H NMR
δ: 4.779 (dd, J＝5.6, 4.4 Hz, 1H), 4.3477 (hept, J＝6.7
Hz, 1H), 4.221—4.128 (m, 2H), 3.846 (hept, J＝6.3 Hz,
1H), 2.959 (dd, J＝17.0, 4.3 Hz, 1H), 2.830 (dd, J＝
17.0, 5.7 Hz, 1H), 1.433 (d, J＝6.9 Hz, 3H), 1.423 (d,
J＝6.8 Hz, 3H), 1.258 (t, J＝7.2 Hz, 3H), 1.099 (d, J＝
6.35 Hz, 3H), 1.069 (d, J＝6.35 Hz, 3H); 13C NMR
(CDCl3, 125 MHz) δ: 171.36, 168.57, 145.93, 74.15,
61.20, 45.90, 45.46, 35.76, 24.32,－24.09, 18.89, 18.70,
(CDCl3, 500 MHz) δ: 4.719 (hept, J＝6.9 Hz, 1H), 3.93
(q, J＝7.15 Hz, 1H), 3.375 (hept, J＝6.2 Hz, 1H), 1.590
(d, J＝7.15 Hz, 3H), 1.407 (d, J＝6.95 Hz, 3H), 1.401
(d, J＝6.95 Hz, 3H), 1.162 (d, J＝6.0 Hz, 3H), 1.153 (d,
J＝6.0 Hz, 3H); 13C NMR (CDCl3, 125 MHz) δ: 175.03,
147.46, 53.73, 47.18, 41.51, 23.51, 23.49, 19.71, 18.6＋3,
－1
18.61; IR v: 1723, 1642 cm ; MS m/z (%): 214 ([M] ,
1
96), 199 (42), 186 (6), 171 (43), 157(100), 143 (84), 129
(52), 111 (18), 101 (12), 83 (61), 69 (79), 58 (64), 43
(60), 27 (27). HRMS calcd for C10H18N2OS ([M]＋)
214.1134, found 214.1107.
14.18; IR v: 1743, 1710, 1407 cm ; MS m/z (%): 270
([M]＋, 77), 255 (88), 229 (70), 228 (51), 227 (41), 213
(100), 187 (21), 167 (18), 155 (10), 141 (27), 127 (82),
113 (8), 98 (45), 84 (31), 71 (26), 70 (41), 69 (62), 55
(59), 43 (60), 29 (28). HRMS calcd for C13H22N2O4
([M]＋) 270.1574, found 270.1578.
3h: liquid, Rf＝0.47 [V(EA)/V(PE)＝5/95]. 1H NMR
(CDCl3, 500 MHz) δ: 4.297 (tt, J＝12.3, 3.8 Hz, 1H),
3.933 (q, J＝7.15 Hz, 1H), 3.090—3.039 (m, 1H),
2.40—2.30 (m, 2H), 1.814—1.756 (m, 4H), 1.719—
1.686 (m, 2H), 1.645—1.612 (m, 1H), 1.591—1.546 (m,
References
5 H), 1.454—1.272 (m, 8H), 1.230—1.139 (m, 1H); 13C
1
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55.41, 41.56, 33.44, 28.11, 28.06,－26.18, 25.85, 25.35,
1
2
(a) Mathias, L. J. Synthesis 1979, 561.
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24.35, 19.92; IR v: 1723, 1636 cm ; MS m/z (%): 294
([M]＋, 7), 237 (14), 215 (27), 214 (57), 213 (100), 183
(17), 169 (10), 157 (11), 131 (83), 110 (10), 98 (16), 81
(29), 67 (14), 55 (47),＋41 (29), 29 (5). HRMS calcd for
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3i: colorless solid, m.p. 52—54 ℃; Rf ＝0.68
1
[V(EA)/V(PE)＝2/5]. [α]2D5 90.0 (c 0.2, CH2Cl2). H
3
(a) Chighine, A.; Crosignani, S.; Arnal, M.-C.; Bradley, M.;
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2004, 69, 5897.
NMR (CDCl3, 500 MHz) δ: 4.823 (d, J＝1.5 Hz, 1H),
4.612 (dd, J＝5.95, 1.5 Hz, 1H), 4.410—4.300 (m, 3H),
3.826 (hept, J＝6.9 Hz, 1H), 3.080 (hept, J＝6.0 Hz,
4
(a) Crosignani, S.; Young, A. C.; Linclau, B. Tetrahedron
Lett. 2004, 45, 9611.
1H), 1.422 (d, J＝7.0 Hz, 3H), 1.408 (d, J＝6.9 Hz, 3H),
1.344 (dt, J＝7.2 Hz, 3H), 1.090 (d, J＝6.3 Hz, 6H); 13C
NMR (CDCl3, 125 MHz) δ: 170.92, 168.14, 145.85,
78.25, 69.65, 62.81, 45.98, 45.66, 24.21, 23.93, 18.95,
(b) Aresta, M.; Dibenedetto, A.; Fracchiolla, E.; Giannoc-
caro, P.; Pastore, C.; Paopai, I.; Schube, G. J. Org. Chem.
2005, 70, 6177.
－1
18.68, 14.09; I＋R v: 1757, 1710, 1434 cm ; MS m/z (%):
287 ([M＋ 1] , 19), 286 ([M]＋, 93), 271 (100), 245
5
(a) Zohrabi-Kalantari, V.; Heidler, P.; Larsen, T.; Link, A.
Org. Lett. 2005, 7, 5665.
(83), 229 (61), 211 (34), 185 (7), 171 (35), 155 (6), 143
(20), 127 (49), 115 (7), 99 (6), 83 (8), 71 (20), 69 (19),
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44, 8143.
6
58 (16), 43 (19), 29 (7). HRMS calcd for C13H22N2O5
([M]＋) 286.1523, found 286.1529.
7
(a) Schmidt, E.; Carl, W. Justus Liebigs Ann.Chem. 1961,
639, 24.
3j: colorless solid, m.p. 112—114 ℃; Rf ＝0.67
1
[V(EA)/V(PE)＝2/5]. [α]2D5 70.5 (c 0.20, CH2Cl2). H
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NMR (CDCl3, 500 MHz) δ: 4.814 (d, J＝1.5 Hz, 1H),
8
4.607 (dd, J＝6.15, 1.55 Hz, 1H), 4.408—4.306 (m, 2H),
3.945 (tt, J＝12.3, 3.85 Hz, 1H), 3.508—3.472 (m, 1H),
9
Rapi, G.; Sbrana, G.; Gelsomini, J. J. Chem. Soc. C 1971,
3827.
3.032 (d, J＝6.1 Hz, 1H), 2.283—2.181 (m, 2H), 1.804
(d, J＝12.95 Hz, 2H), 1.729—1.622 (m, 7H), 1.559 (d,
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Chin. J. Chem. 2011, 29, 303— 308