Catalyzed addition of diazoacetoacetates to imines: Synthesis of highly functionalized aziridines

Article abstract of DOI:10.1039/b813763c

The addition of diazoacetoacetates to aromatic imines derived from p-methoxyaniline is achieved using dirhodium tetraacetate as the catalyst. Highly functionalized aziridines are obtained in good yield and with excellent stereoselectivity. 2-Diazo-1,3-diketones also provide good yields of aziridines, but dimethyl diazomalonate is inactive in the transformation. The diazoacetoacetates of chiral alcohols are also examined in the reaction and moderate diastereoselectivity is achieved with (R)-pantolactone-derived diazoacetoacetate. A reaction mechanism through metal-carbene and azomethine ylide is proposed.

Full text of DOI:10.1039/b813763c

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Catalyzed addition of diazoacetoacetates to imines: synthesis of highly
functionalized aziridines†
Xue-jing Zhang,a Ming Yan*a and Dan Huang*b
Received 7th August 2008, Accepted 14th October 2008
First published as an Advance Article on the web 10th November 2008
DOI: 10.1039/b813763c
The addition of diazoacetoacetates to aromatic imines derived from p-methoxyaniline is achieved using
dirhodium tetraacetate as the catalyst. Highly functionalized aziridines are obtained in good yield and
with excellent stereoselectivity. 2-Diazo-1,3-diketones also provide good yields of aziridines, but
dimethyl diazomalonate is inactive in the transformation. The diazoacetoacetates of chiral alcohols are
also examined in the reaction and moderate diastereoselectivity is achieved with (R)-pantolactone-
derived diazoacetoacetate. A reaction mechanism through metal-carbene and azomethine ylide is
proposed.
1. Introduction
2. Results and discussion
Aziridines are highly useful synthetic intermediates in organic
synthesis and structural units of many natural products and
drugs.1 Various synthetic methods of aziridines,2 including sev-
eral asymmetric versions,3 have been reported. Among them,
the addition of carbenes generated from diazo compounds to
imines is highly attractive considering the anticipated good yield,
high product stereoselectivity, and ease of procedure. Transi-
tion metal complexes,4 Lewis acids,5 Brønsted acids,6 lithium
perchlorate7 and ionic liquids8 have been found to promote
efficiently the addition of diazoacetates to imines. The corre-
sponding aziridinecarboxylates are prepared generally in good
yields. In addition to diazoacetates, other diazo compounds such
as TMSCHN2,9 diazophosphonates,10 phenyldiazoactetates and
styryldiazoacetates11 were also successfully applied. On the other
hand, addition of diazoacetoacetates to imines is also an attractive
research subject and the reaction provides highly functionalized
aziridines. They can be used to prepare b-hydroxy-a-amino acids,
which are important synthetic intermediates for many natural
products and drugs.12 In addition they are susceptible to ring
opening reaction with various nucleophilic agents to provide a
number of useful compounds.13 However, in a previous study
the addition of diazoacetoacetates to imines failed to provide
desired aziridines, probably due to their lower reactivity com-
pared to diazoacetates.5g In this paper we report the rhodium-
catalyzed reaction of diazoacetoacetates with imines derived from
p-methoxyaniline. Highly functionalized aziridines are obtained
in good yield and with excellent cis-selectivity.
2.1 Study of catalysts and reaction conditions
The reaction of N-benzylidene-4-methoxyaniline (1a) with methyl
diazoacetoacetate (2a) was studied in the presence of rhodium
and copper catalysts. The results are summarized in Table 1. The
use of Rh2(OAc)4 provided the expected aziridine product in good
yield and excellent stereoselectivity. Only the cis-isomer 3a was
observed and its relative configuration was determined by NOE
experiment. The amount of diazo compound exerted a significant
effect on the yield of 3a. When 1.0 equivalent, 1.5 equivalents and
2.0 equivalents of 2a were used, the yield of 3a increased from 69%
to 87%, and to 92%, respectively (Table 1, entries 1–3). This result
implied the partial loss of 2a under the reaction conditions. The
higher reaction temperature of 1,2-dichloroethane (b.p. 81 ◦C) was
favorable, since lower yield of 3a was obtained in dichloromethane
(b.p. 39 ◦C) (Table 1, entry 4 vs. entry 1).
Table 1 Addition of 2a to 1a catalyzed by rhodium and copper catalysts.a
Entry
Catalyst
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
Rh2(OAc)4 (1 mol%)
Rh2(OAc)4 (1 mol%)
Rh2(OAc)4 (1 mol%)
Rh2(OAc)4 (1 mol%)
Cu(hfacac)2 (3 mol%)
Cu(acac)2 (3 mol%)
CuPF6 (3 mol%)
2
2
2
2
2
2
3
6
87
92c
69d
35e
30
30
20
aIndustrial Institute of Fine Chemicals and Synthetic Drugs, School of
Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510080,
China. E-mail: yanming@mail.sysu.edu.cn; Fax: 86-20-39943049
Cu(OTf)2 (3 mol%)
~0
bThe School of Textiles & Clothing, Jiangnan University, Wuxi, 214122,
China. E-mail: huangdan6@163.com
a The reactions were carried out in refluxing 1,2-dichloroethane with 1a
(1 mmol) and 2a (1.5 mmol). b Isolated yield based on 1a. c 2 mmol 2a was
used. d 1mmol 2a was used. e CH2Cl2 was used as the reaction solvent.
† CCDC reference number 682854. For crystallographic data in CIF or
other electronic format see DOI: 10.1039/b813763c
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Table 2 The reaction of 2a with imines derived from a variety of aldehydes
and p-methoxy anilinea
Use of copper salts such as Cu(hfacac)2, Cu(acac)2 and CuPF6
gave low yields of 3a, but Cu(OTf)2 was totally ineffective in this
reaction. Since Cu(OTf)2 is the strongest Lewis acid among the
tested copper salts, the result suggested that the reaction did not
proceed through the Lewis acid catalytic addition of the diazo
compound to the imine. A metal carbene route is consistent with
this information.14
2.2 The effect of electronic property of imines
Entry
Imine
R1
Product (yield (%))b
Furthermore imines 1a–1c with different electronic properties
were examined in the reaction with 2a, and the results are
illustrated in Scheme 1. The electronic properties of imines show
profound effects on the reaction. Imine 1c with a strong electron-
withdrawing group (4-NO2) was completely inactive. In contrast
imine 1a with an electron-donating group (4-MeO) provided
aziridine 3a in good yield. Unsubstituted imine 1b gave 51% yield
of aziridine 4. An additional advantage using imine 1a was that
4-MeO-phenyl could be removed readily by oxidization to provide
1-H aziridines in good yield (Scheme 2).11
1
2
3
4
5
6
7
8
1a
1d
1e
1f
1g
1h
1i
Ph
3a (87)
3d (99)
3e (99)
p-MeO-Ph
o-MeO-Ph
p-NO2-Ph
p-Cl-Ph
o-Cl–Ph
2-naphthyl
2-pyridinyl
c
—
3g (94)
3h (89)
3i (97)
c
1j
—
a The reactions were carried out in refluxing 1,2-dichloroethane with 1
(1 mmol) and 2a (1.5 mmol). b Isolated yield based on 1. c No reaction.
hyde, gave a complex mixture of products, and no substantial
amount of aziridine products could be isolated.
2.4 The reaction of imine 1a with a variety of diazo compounds
Furthermore diazoacetoacetone (2b), 2-diazo-1-phenylbutane-
1,3-dione (2c), dimethyl diazomalonate (2d) and diazoacetoacetate
of chiral alcohols (2e–2i) were prepared (Scheme 3) and examined
in the reaction with 1a. The results are summarized in Table 3.
Both 2b and 2c gave the corresponding aziridines in good yield.
2d was inactive in the reaction. (1R)-endo-(+)-Fenchol-derived
diazoacetoacetate 2e provided aziridine 6 in 77% yield and
low diastereoselectivity (d.r. = 1.3:1). (R)-Pantolactone-derived
diazoacetoacetate 2f afforded aziridine 7 in 69% yield and better
diastereoselectivity (d.r. = 3:1). (L)-Menthol-derived diazoace-
toacetate (2g) did not afford the corresponding aziridine product,
instead an intramolecular C–H insertion product 10 was obtained
in 73% yield (Scheme 4).15, which structure was confirmed by
NMR and furthermore by X-Ray diffraction (Fig. 1)16 The
chiral diazoacetoacetates 2h and 2i provided complex mixtures
Scheme 1 The reaction of imines 1a–1c with 2a.
Scheme 2 The reaction of 3a with cerium(IV) ammonium nitrate (CAN).
2.3 The reaction of methyl diazoacetoacetate with imines
The imines derived from p-methoxyaniline and a variety of
aldehydes were examined in the reaction with 2a. The results are
summarized in Table 2. The imines prepared from benzaldehydes
with para- or ortho- methoxy substitutent provided cis-aziridines
in almost quantitative yields (Table 2, entries 2–3). In contrast,
para-nitro substitution completely inhibited the reaction (Table 2,
entries 4). Again the results confirm that the electronic density
of imines is of key importance for this transformation. para- or
ortho-Chloro substitution of benzaldehyde was tolerated very well
(Table 2, entries 5–6). The imine 1i, derived from 2-naphthal-
dehyde, also provided the aziridine in excellent yield. The imine
1j, derived from picolinaldehyde did not react with 2a. The
deactivation of Rh2(OAc)4 by a strong coordination with 1j was
proposed in this case. The other imines derived from thiophene-2-
carbaldehyde, cinnamaldehyde, isobutyraldehyde and pivalalde-
Scheme 3 Diazo compounds 2a-2i.
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Table 3 The reaction of diazo compounds 2a-2g with 1a.a
reaction of diazoacetoacetates had been reported by Doyle and
coworkers.15
2.4 Reaction mechanism
A proposed reaction mechanism is illustrated in Scheme 5. Methyl
diazoacetoacetate is decomposed by rhodium acetate to generate a
metal carbene, which reacts with the imine to provide azomethine
ylide. The consequent intramolecular ring-closing step occurs via
conformation A to provide the cis-aziridine stereoselectively.4e,11
Conformation B is unfavored due to large steric interactions
between the ester group with N-aryl of imine.
Diazo compound
R2
R3
Product (yield (%))b
2a
2b
2c
2d
2e
Me
Me
Me
MeO
Me
OMe
Me
Ph
3a (87)
6 (88)
7 (84)c
(0)
MeO
8 (77)d
2f
Me
9 (69)e
a The reactions were carried out in refluxing dichloroethane with 1a
(1 mmol) and 2a–2i (1.5 mmol). b Isolated yield based on 1a. c Mixture
of cis/trans-aziridine (1/2.2). d Two diastereoisomers (1.3/1). e Two
diastereoisomers (3/1).
Scheme 5 The proposed reaction mechanism.
3. Conclusion
In conclusion, highly functionalized aziridines were prepared in
good yields and excellent stereoselectivities by catalyzed addition
of diazoacetoacetates to imines derived from p-methoxyaniline.
Dirhodium tetraacetate is a better catalyst than copper salts
in this reaction. Diazoacetoacetates of chiral alcohols were
also examined and moderate diastereoselectivity was achieved
with (R)-pantolactone-derived diazoacetoacetate. The reported
reaction provides a new synthetic method of aziridines from
diazoacetoacetates and imines.
Scheme 4 Intramolecular C–H insertion of 2g.
4. Experimental
General details
Fig. 1 ORTEP drawing of 10.
NMR spectra were recorded on a Varian Inova 400 MHz instru-
ment and chemical shifts are reported in parts per million (ppm, d)
downfield from the internal standard. Me4Si (TMS, d = 0) is used
as the internal standard for 1H NMR spectra. 13C NMR spectral
data are reported relative to the central line of the chloroform sig-
nal (d = 77.00 ppm). High-resolution mass spectra were obtained
on JEOL HX110A or GCT-TOF spectrometer. Low-resolution
mass spectra were obtained on a Finnigan LC-MS spectrometer.
Infrared spectra were recorded on Mattson Alpha-Centauri FT-
IR spectrometer, either as a thin film, a nujol mull, or a solution
on sodium chloride plates. The absorptions are reported in wave-
numbers (cm-1). Element analyses were recorded on carlo-Erba
of products, from which no substantial amount of aziridines
could be isolated. These results suggest that C–H insertion
and other side reactions are competitive with the aziridination
reaction for diazoacetoacetates derived from chiral alcohols. The
structure of chiral alcohols has great effects on the reactivity
of the corresponding diazoacetoacetates. The diazoacetoacetates
with available C–H bonds to form insertion products of five-
membered rings (2g, 2h) or with aromatic C–H bond (2i) failed
to give aziridines. For 2e and 2f, no C–H bonds are available to
form insertion products of five-membered rings, so good yields
of aziridines were obtained. A detailed study of C–H insertion
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EA1110 CNNO-S instrument. X-ray diffraction was recorded on
Rigaku Mercury CCD spectrometer. Thin layer chromatography
was performedonMerckSilica Gel40 F254 glass-backed plates. The
visualization was achieved with UV, iodine, or phosphomolybdic
acid. Flash column chromatography was performed on 40–
cis-Mehtyl 1-(4-methoxyphenyl)-2-acetyl-3-(4-chlorophenyl)-
aziridine-2-carboxylate (3g). White solid. M. p. 140–142 ◦C; IR
1
(KBr, cm-1): 1748 (s), 1639 (m), 1618 (m), 1511 (s); H NMR
(CDCl3, 400 MHz) d 7.30-7.22 (m, 6H), 6.82 (d, J = 9.2 Hz,
2H), 4.83 (s, 1H), 3.76 (s, 3H), 3.32 (s, 3H), 1.79 (s, 3H); 13C NMR
(CDCl3, 100 MHz) d 168.5, 163.3, 156.4, 134.7, 132.1, 130.5, 128.7,
128.1, 118.4, 114.4, 66.0, 65.5, 55.4, 51.9, 17.5; HRMS (EI) calc.
for C19H18O4N1Cl (M+): 359.0919, found: 359.0917.
˚
63 mm, 230–400 mesh, 60A silica gel. Dichloromethane and 1,2-
dichloroethane were distilled over calcium hydride. Other solvents
were used as their commercial anhydrous grade. Chemicals were
purchased form Aldrich or Acros chemical company. The imines
1a-1j were prepared by reflux of corresponding aldehydes (1
equivalent) and anilines (1 equivalent) in ethanol for 1–2 hours.
Generally crystal imines in good purity were obtained after cooling
of the reaction mixture. The diazo compounds 2a-2i were prepared
via treatment of corresponding acetoacetates or 1,3-diketones with
methanesulfonyl azide and triethylamine according to reported
procedures.15
cis-Methyl 1-(4-methoxyphenyl)-2-acetyl-3-(2-chlorophenyl)-
aziridine-2-carboxylate (3h). White solid. M. p. 116–118 ◦C; IR
(KBr, cm-1): 1749 (m), 1637 (s), 1618 (s), 1514 (m), 1455 (m);
1H NMR (CDCl3, 400 MHz) d 7.43 (dd, J = 1.2, 8.0 Hz, 1H),
7.27-7.14 (m, 5H), 6.84 (d, J = 8.8 Hz, 2H), 5.32 (s, 1H), 3.77 (s,
3H), 3.26 (s, 3H), 1.89 (s, 3H); 13C NMR (CDCl3, 100 MHz) d
168.3, 163.6, 156.4, 133.4, 131.5, 130.6, 129.7, 129.6, 128.1, 126.4,
118.4, 114.4, 65.7, 62.7, 55.4, 51.8, 17.5; HRMS (EI) calc. for
C19H18O4N1Cl1 (M+): 359.0919, found: 359.0918.
Representative experimental procedure for the catalyzed addition
of diazoacetoacetates to imines
cis-Methyl 1-(4-methoxyphenyl)-2-acetyl-3-(naphthalen-2-yl)-
◦
aziridine-2-carboxylate (3i). White solid. M. p. 142–143 C; IR
A solution of methyl diazoacetoacetate 2a (213 mg, 1.5 mmol)
in ClCH2CH2Cl (4 mL) was added via a syringe pump over one
hour to a refluxing solution of Rh2(OAc)4 4.4 mg (0.01 mmol)
and benzylidene-p-methoxyaniline 1a (211 mg, 1.0 mmol) in
ClCH2CH2Cl (8 mL). The resulting solution was allowed to reflux
for another hour. The reaction mixture was filtered through a
short silica plug, which was washed with ClCH2CH2Cl (10 mL).
The solvent was removed and the crude product was purified by
flash column chromatography on silica gel (hexane: ethyl acetate =
3: 1) afforded 3a as a colorless oil (284 mg, 87%).
(KBr, cm-1): 1753 (s), 1736 (s), 1602 (m), 1511 (s), 1446 (m), 1245
1
(s); H NMR (CDCl3, 400 MHz) d 7.82-7.76 (m, 3H), 7.50-7.47
(m, 2H), 7.37 (dd, J = 2.0, 8.8 Hz, 2H), 7.30-7.26 (m, 2H), 6.79 (d,
J = 9.2 Hz, 2H), 5.02 (s, 1H), 3.74 (s, 3H), 3.19 (s, 3H), 1.85 (s, 3H);
13C NMR (CDCl3, 100 MHz) d 168.7, 163.7, 156.2, 133.3, 132.9,
131.1, 130.9, 128.3, 127.9, 127.7, 126.5, 126.4, 126.3, 123.9, 118.5,
114.3, 66.4, 66.1, 65.3, 51.8, 17.7; HRMS (EI) calc. for C23H21O4N1
(M+): 375.1465, found: 375.1464.
cis-methyl 2-acetyl-1,3-diphenyl-aziridine-2-carboxylate (4).
1
Colorless oil. H NMR (CDCl3, 400 MHz) d 7.34-7.32 (m, 5H),
cis-Methyl 1-(4-methoxyphenyl)-2-acetyl-3-phenyl-aziridine-2-
carboxylate (3a). IR (film, cm-1): 1744 (s), 1610 (m), 1511 (s),
7.29-7.23 (m, 4H), 7.09 (t, J = 7.3 Hz, 1H), 4.90 (s, 1H), 3.26 (s,
3H), 1.80 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 168.56, 164.15,
137.31, 133.38, 129.09, 128.78, 128.49, 126.65, 124.26, 117.23,
66.14, 65.94, 51.81, 17.58; HRMS (FAB) calc. for C18H18NO3
(M+ + 1): 296.1287, found: 296.1285.
1
1245 (m); H NMR (CDCl3, 400 MHz) d 7.36-7.29 (m, 3 H),
7.28-7.24 (m, 4 H), 6.80 (d, J = 9.0 Hz, 2 H), 4.87 (s, 1 H), 3.73
(s, 3 H), 3.25 (s, 3 H), 1.78 (s, 3 H); 13C NMR (CDCl3, 100 Hz)
d 168.58, 163.49, 156.16, 133.42, 130.75, 128.65, 128.36, 126.60,
118.41, 114.22, 66.06, 65.84, 55.30, 51.66, 17.43; HRMS (FAB)
calc. for C19H19NO4 (M+): 325.1314, found: 325.1330.
1-(4-Methoxyphenyl)-2,2-diacetyl-3-phenyl-aziridine (6). Col-
orless oil. 1H NMR (CDCl3, 400 MHz) d 7.45-7.39 (m, 2H), 7.36-
7.29 (m, 3H), 7.12 (d, J = 9.0 Hz, 2H), 6.79 (d, J = 9.0 Hz, 2H), 6.42
(s, 1H), 3.72 (s, 3 H), 1.90 (s, 3H), 1.77 (s, 3H); 13C NMR (CDCl3,
100 MHz) d 163.54, 158.58, 137.20, 132.68, 128.97, 128.27, 127.08,
126.82, 113.93, 106.65, 88.91, 55.22, 17.30, 10.24; HRMS (FAB+)
calc. for C19H19NO3 (M+): 309.1365, found: 309.1367.
cis-Mehtyl 2-acetyl-1,3-bis (4-methoxyphe◦nyl)-aziridine-2-car-
boxylate (3d). White solid. M. p. 100–102 C; IR (KBr, cm-1):
1757 (s), 1614 (m), 1514 (s), 1457 (m), 1390 (m); 1H NMR (CDCl3,
400 MHz) d 7.27 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H),
6.85 (d, J = 8.8 Hz, 2H), 6.81 (d, J = 8.8 Hz, 2H), 4.81 (s, 1H),
3.78 (s, 3H), 3.76 (s, 3H), 3.32 (s, 3H), 1.77 (s, 3H); 13C NMR
(CDCl3, 100 Hz) d 168.8, 163.8, 159.9, 156.2, 130.8, 128.0, 125.2,
118.5, 114.3, 113.9,66.0, 65.9, 55.4, 55.2, 51.8, 17.4; HRMS (EI)
calc. for C20H21O5N1 (M+): 355.1414, found: 355.1413.
1-(4-Methoxyphenyl)-2-acetyl-2-benzoyl-3-phenyl-aziridine (7).
Colorless oil, cis-isomer. 1H NMR (CDCl3, 400 MHz) d 7.56-7.49
(m, 2H), 7.43-7.36 (m, 3H), 7.31-7.18 (m, 5H), 7.14 (d, J = 9.0 Hz,
2H), 6.82 (d, J = 9.0 Hz, 2H), 6.59 (s, 1H), 3.75 (s, 3H), 1.84 (s, 3H);
13C NMR (CDCl3, 100 MHz) d 162.23, 160.92, 157.70, 137.23,
133.35, 132.67, 130.85, 129.29, 128.52, 127.86, 127.23, 126.89,
114.87, 114.10, 90.33, 89.50, 55.42, 18.63; HRMS (FAB+) calc.
for C24H21NO3 (M+): 371.1521, found: 371.1513.
cis-Methyl 1-(4-methoxyphenyl)-2-acetyl-3-(2-methoxyphenyl)-
aziridine-2-carboxylate (3e). White solid. M. p. 104–105 ◦C; IR
1
(KBr, cm-1): 1749 (m), 1637 (s), 1618 (s), 1514 (s), 1455 (m); H
NMR (CDCl3, 400 MHz) d 7.32-7.26 (m, 3H), 7.08 (dd, J = 1.6,
7.6 Hz, 1H), 6.85 (dd, J = 1.2, 8.0 Hz, 1H), 6.85-6.83 (m, 3H),
5.22 (s, 1H), 3.88 (s, 3H), 3.77 (s, 3H), 3.21 (s, 3H), 1.80 (s, 3H);
13C NMR (CDCl3, 100 MHz) d 168.9, 164.2, 157.3, 156.1, 131.1,
129.3, 127.2, 122.1, 119.9, 118.5, 114.3, 110.3, 65.3, 61.1, 55.5,
55.4, 51.5, 17.0; HRMS (EI) calc. for C20H21O5N1 (M+): 355.1414,
found: 355.1412.
trans-isomer. 1H NMR (CDCl3, 400 MHz) d 7.55 (d, J =
8.4 Hz, 2H), 7.45-7.34 (m, 8 H), 7.19 (d, J = 9.0 Hz, 2H), 6.84
(d, J = 9.0 Hz, 2H), 6.60 (s, 1H), 3.76 (s, 3H), 1.95 (s, 3H);
13C NMR (CDCl3, 100 MHz) d 164.50, 157.76, 156.55, 136.87,
133.05, 132.59, 130.04, 129.31, 129.15, 128.54, 128.11, 127.44,
126.84, 114.14, 107.97, 89.39, 55.39, 12.04; HRMS (FAB+) calc.
for C24H21NO3 (M+): 371.1521, found: 371.1532.
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1,3,3-Trimethylbicyclo[2.2.1]heptan-2-yl 1-(4-methoxyphenyl)-
2-acetyl-3-phenyl-aziridine-2-carboxylate (8). Major isomer. IR
(KBr, cm-1): 1755 (s), 1716 (s), 1585 (m), 1512 (m), 1458 (m),
1396 (m), 1292 (s), 1176 (m), 1157 (m), 1030 (m), 956 (w), 694
(w); 1H NMR (CDCl3, 400 MHz) d 7.31-7.26 (m, 5H), 7.24
(d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.4 Hz, 2H), 4.86 (s, 1H),
3.99 (s, 1H), 3.75 (s, 3H), 1.82 (s, 3H), 1.69-1.42 (m, 2H), 1.39-
1.26 (m, 3H), 1.08-0.96 (m, 2H), 0.96 (s, 3H), 0.92 (s, 3H), 0.55
(s, 3H); 13C NMR (CDCl3, 100 MHz) d 164.4, 156.6, 129.3,
127.6, 127.4, 119.1, 114.7, 87.9, 67.0, 55.9, 48.7, 41.7, 39.9, 29.8,
26.8, 26.2, 23.2, 20.7, 19.4, 19.2, 18.7; HRMS (EI+) calc. for
C28H33NO4 (M+): 447.2410, found: 447.2374; Anal. Calc. for
C28H33NO4: C, 75.14; H, 7.43; N, 3.13, found: C, 75.14; H, 7.45; N,
3.13.
Reaction of aziridine 3a with cerium(IV) ammonium nitrate
To a solution of 3a (168 mg, 0.5 mmol) in acetonitrile (7 mL) under
an ice-bath was added a solution of cerium(IV) ammonium nitrate
(685 mg, 1.25 mmol) in 4 mL of water. The reaction mixture was
stirred for 2 hours and 5% aqueous NaHCO3 solution was added
at 0 ◦C until pH of the solution was almost neutral. The resulting
mixture was allowed to warm up to room temperature. The solid
sodium sulfite was added portionwise until a brown slurry was
formed. After AcOEt (10 mL) was added, the organic layer was
separated and dried over anhydrous sodium sulfate. The solvent
was removed under vacuum and the residue was purified by flash
column chromatography on silica gel (hexane: ethyl acetate = 3:
1) to afford cis-methyl 2-acetyl-3-phenyl-aziridine-2-carboxylate
(5) as a white solid (68 mg, 62% yield). M. p. 128–130 ◦C; IR
1
Minor isomer. H NMR (CDCl3, 400 MHz) d 7.31-7.26 (m,
1
(KBr, cm-1): 1741 (s), 1600 (m), 1453 (m), 1250 (m); H NMR
5H), 7.21 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 4.86 (s,
1H), 3.94 (s, 1H), 3.74 (s, 3H), 1.82 (s, 3H), 1.69-1.42 (m, 2 H),
1.39-1.26 (m, 3H), 1.08-0.96 (m, 2H), 0.98 (s, 3H), 0.67 (s, 3H), 0.43
(s, 3H); 13C NMR (CDCl3, 100 MHz) d 164.4, 156.6, 129.3, 127.6,
127.4, 119.1, 114.7, 87.9, 67.0, 55.9, 48.7, 41.7, 39.9, 29.8, 26.8,
26.2, 23.2, 20.7, 19.4, 19.2, 18.7; HRMS (EI+) calc. for C28H33NO4
(M+): 447.2410; found: 447.2374.
(CDCl3, 400 MHz) d 7.32-7.26 (m, 5H), 4.63 (s, 1H), 3.24 (s, 3H),
1.76 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 168.8, 167.8, 135.6,
128.5, 128.3, 126.1, 67.5, 63.0, 51.7, 17.2; HRMS (FAB) calc. for
C12H13O3N1 (M+): 219.0890, found: 219.0886.
Acknowledgements
We thank the National Natural Science Foundation of China
(No. 20472061, 20772160), NCET plan of Ministry of Education
of China, Guangzhou Bureau of Science and Technology for
financial support of this study. We also thank Prof. Michael P.
Doyle for his help and suggestions.
Tetrahydro-4,4-dimethyl-2-oxofuran-3-yl 1-(4-methoxyphenyl)-
2-acetyl-3-phenyl-aziridine-2-carboxylate (9). Major isomer. IR
(KBr, cm-1): 1763 (s), 1734 (s), 1609 (s), 1583 (m), 1510 (m), 1466
(m), 1373 (m), 1292 (m), 1246 (m), 1178 (w), 1161 (m), 823 (m),
594 (w); 1H NMR (CDCl3, 400 MHz) d 7.51 (d, J = 6.4 Hz, 2H),
7.28 (d, J = 9.2 Hz, 3H), 6.92 (d, J = 9.2 Hz, 2H), 6.79 (d, J =
9.2 Hz, 2H), 4.99 (s, 1H), 4.58 (s, 1H), 4.21 (d, J = 9.6 Hz, 1H),
4.04 (d, J = 9.6 Hz, 1H), 3.72 (s, 3H), 2.0 (s, 3H), 1.39 (s, 3H),
1.23 (d, J = 8.4 Hz, 3 H); 13C NMR (CDCl3, 100 MHz) d 196.9,
164.6, 155.04, 137.2, 133.9, 129.2, 118.8, 115.4, 114.6, 114.5, 83.7,
79.9, 65.5, 60.9, 55.9, 55.8, 40.0, 28.5, 21.7; HRMS (EI+) calc.
for C24H25NO6 (M+): 423.1682, found: 423.1641; Anal. Calc. for
C24H25NO6 : C, 68.07; H, 5.95; N, 3.31, found: C, 67.62; H, 6.01;
N, 3.27.
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16 CCDC-682854 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB21EZ,
UK; fax (t44) 1223-336-033; or deposit@ccdc.cam.ac.uk].
192 | Org. Biomol. Chem., 2009, 7, 187–192
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The Royal Society of Chemistry 2009
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