Lewis acid catalyzed reactions of donor-acceptor cyclopropanes with 1- and 2-pyrazolines: Formation of substituted 2-pyrazolines and 1,2-diazabicyclo[3.3. 0]octanes

Article abstract of DOI:10.1016/j.tet.2010.09.092

The reaction of 2-substituted cyclopropane-1,1-dicarboxylates with 1- and 2-pyrazolines is efficiently catalyzed by scandium or ytterbium triflates to give N-substituted 2-pyrazolines or 1,2-diazabicyclo[3.3.0]octanes. The reactions of 2-pyrazolines give diazabicyclooctanes as the major products. In contrast, the reactions starting from 1-pyrazolines predominantly give N-substituted 2-pyrazolines, which become the major compounds obtained if an equimolar amount of GaCl₃ is used. A possible reaction mechanism is suggested.

Full text of DOI:10.1016/j.tet.2010.09.092

Tetrahedron 66 (2010) 9151e9158
Contents lists available at ScienceDirect
Tetrahedron
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Lewis acid catalyzed reactions of donoreacceptor cyclopropanes with 1- and
2-pyrazolines: formation of substituted 2-pyrazolines and 1,2-diazabicyclo[3.3.0]
octanes
*
Yury V. Tomilov , Roman A. Novikov, Oleg M. Nefedov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 July 2010
Received in revised form 8 September 2010
Accepted 28 September 2010
Available online 14 October 2010
The reaction of 2-substituted cyclopropane-1,1-dicarboxylates with 1- and 2-pyrazolines is efficiently
catalyzed by scandium or ytterbium triflates to give N-substituted 2-pyrazolines or 1,2-diazabicyclo
[3.3.0]octanes. The reactions of 2-pyrazolines give diazabicyclooctanes as the major products. In contrast,
the reactions starting from 1-pyrazolines predominantly give N-substituted 2-pyrazolines, which be-
come the major compounds obtained if an equimolar amount of GaCl3 is used. A possible reaction
mechanism is suggested.
Keywords:
Cyclopropanedicarboxylates
Pyrazolines
Ó 2010 Elsevier Ltd. All rights reserved.
1,2-Diazabicyclo[3.3.0]octanes
Lewis acid
Catalysis
EDG
EDG
EWG
EWG
1. Introduction
A=B
A
A
B
LA
It is known that cyclopropanes with electron-donating and
electron-withdrawing substituents at the vicinal position can un-
dergo opening of the three-membered ring1 upon thermolysis or
EDG
EWG
LA
C
EDG
EWG
B
A
C
under catalysis by Lewis acids due to cleavage of the s-1,2-bond of
B
the cyclopropane ring. The resulting dipolar intermediate can enter
formal [2þ3]- or [3þ3]-cycloaddition with double and triple bonds
and with 1,3-dipoles to give five- or six-membered rings, including
rings containing heteroatoms (Scheme 1). Reactions of
donoreacceptor cyclopropanes with alkenes,2,3 acetylenes,4,5
aldehydes,6e8 isocyanates,9 imines,10e12 diazenes,13,14 nitriles,15,16
LA – Lewis acid; EDG – electron-donating group; EWG – electron-withdrawing group
Scheme 1.
triflates6 and rare-earth triflates20,23 as well as chloroalanes2 are
the most popular Lewis acids; gallium and indium compounds14
are less common. Examples of enantioselective [2þ3]-cycloaddi-
tion of cyclopropanedicarboxylates with nitrones have been
reported, where Lewis acids with chiral ligands were used as
catalysts.20
Two studies have been published dealing with reactions of
donoreacceptor cyclopropanes with compounds incorporating an
N]N bond.13,14 One of them13 reports the addition of methyl 2,2-
dimethoxycyclopropane-1-carboxylate to diazene derivatives un-
der thermolysis conditions, while the other one14 describes the
addition of 2-substituted dimethyl cyclopropane-1,1-dicarbox-
ylates to diazene derivatives catalyzed by gallium trichloride; both
reactions result in substituted pyrazolidines.
a,b
-unsaturated ketones,17 azomethineimines,18 and nitrones19e21
have been reported. Recently,22 the reaction of hydrazinoethyl 1,1-
cyclopropanediesters with aldehydes in the presence of catalytic
Yb(OTf)3 was carried out as intramolecular cyclization into 1,2-
diazabicyclo[3.3.0]octane derivatives. The products of these re-
actions are used as convenient synthons to obtain various classes of
organic compounds, primarily ones that are of interest as bi-
ologically active compounds.10,16,21,23
Aryl, and sometimes alkyl or alkoxy groups, are used as elec-
tron-donating substituents in cyclopropanes, whereas alkox-
ycarbonyls are used as electron-withdrawing substituents. Tin(II)
Reactions of donoreacceptor cyclopropanes with 1- or 2-pyr-
azolines containing N]N or C]N bonds have not yet been studied.
In turn, successful implementation of these reactions might result
* Corresponding author. Tel./fax: þ7 499 135 6390; e-mail address: tom@ioc.ac.ru
(Y.V. Tomilov).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.092

9152
Y.V. Tomilov et al. / Tetrahedron 66 (2010) 9151e9158
in derivatives of 1,5- or 1,2-diazabicyclo[3.3.0]octanes (Scheme 2)
that are of interest as biologically active compounds and as acces-
sible synthons for constructing various nitrogen-containing het-
erocyclic compounds.
NOE spectra (Fig. 1). The 2D 1H NOESY spectrum of anti-5a features
a cross-peak between the signals of H-8 ( 4.10) and protons of the
CH3-group ( 1.52) as opposed to syn-5a, which features a cross-peak
d
d
between the signals of CH3 (d 1.45) and H-5 (d 4.49).
2.4
3.3
EWG
EWG
MeO2C
MeO2C
MeO2C
H
N
H
EDG
EWG
N
N
N
N
MeO2C
3.2
N
NH
CH3
CO2CH3
CH3
+
N
3.4
N
H
H
H
Lewis acid
N
CO2CH3
EDG
EDG
H
H
N
N
Scheme 2.
H
H
syn-5a
anti-5a
2. Results and discussion
Fig.1. Key cross-peaks in 2D 1H NOESY spectra of anti- and syn-5a.
In order to optimize the reaction conditions and determine the
reaction direction, we chose dimethyl 2-phenylcyclopropane-1,1-
dicarboxylate (1a) and isomeric pyrazolines 2a and 3a as the
starting reagents. Prolonged refluxing in the absence of Lewis acids
does not cause compounds 1a and 2a to react. However, cyclopro-
pane 1a reacts with pyrazolines 2a or 3a in the presence of scan-
dium, indium, or ytterbium triflates even at room temperature,
Sc(OTf)3 being the most efficient of the catalysts used. Complete
conversion of cyclopropane 1a in the presence of Sc(OTf)3 takes 3
days (1 mol % of the catalyst) or 10e12 h (5 mol %). In all cases,
N-substituted 2-pyrazoline 4a and fused pyrazolidine 5a are the
main reaction products from cyclopropane 1a both with 1-pyrazo-
line 2a and with 2-pyrazoline 3a (Scheme 3, Table 1); both products
are formed as mixtures of two diastereomers in a about 1:1 ratio.
As one can see from the structure of compounds 4a and 5a, the
formation of these structures formally involves the addition of
the 1,3-dipolar intermediate, which is formed due to opening of the
cyclopropane ring, either to the NeH bond or to the C]N bond in
2-pyrazoline 3a as a result of preliminary isomerization of 1-pyr-
azoline 2a. However, although the same compounds 4a and 5a are
formed, their ratio depends considerably on the nature of the
starting pyrazolines 2a or 3a. In fact, the reaction using 1-pyrazo-
line 2a produces two times as much pyrazoline 4a as pyrazolidine
5a, whereas their ratio is reversed in the case of 2-pyrazoline 3a
(Table 1). Ytterbium triflate acts less readily; however, the selec-
tivities of formation of compounds 4a and 5a in the presence of this
compound are the same as in the case of Sc(OTf)3.
CO2Me
Me
CO2Me
CO2Me
N
R
CO2Me
N
N
N
MeO2C
N
Lewis
acid
CH2Cl2
MeO2C
Me
CO2Me
Me
2a
+
or
+
N
N
CO2Me
Me
R
R
H
MeO2C
CO2Me
4a–c
NH
1a–c
3a
5a,b
R = C6H5 (a); 2-Thienyl (b); H (c)
Scheme 3.
Stereoisomers5acanbeeasilyseparatedfromeachotherandfrom
isomeric pyrazolines 4a by means of column chromatography. The
fact that only two isomers of 5a out of four are formed is due to steric
factors, which ensure that only the anti-8-phenyl-1,2-diazabicyclo
[3.3.0]octane fragment with varying orientation of substituents at
C(3) is formed. The structures of anti- and syn-5a are confirmed by
The use of anhydrous GaCl3 also ensures that the reaction of
cyclopropanedicarboxylate 1a with pyrazoline 2a will occur, but an
equimolar amount of GaCl3 and cooling to 0 ꢀC are required. No 1,5-
or 1,2-diazabicyclo[3.3.0]octanes are formed at all in this case;
moreover, as concerns 1:1 adducts, only N-substituted 2-pyrazoline
4a (Table 1) is formed as two diastereomers in a 1:1 ratio, just like
in the presence of Sc(OTf)3 or Yb(OTf)3 as catalysts. Ethyl dichlor-
oalane at low temperatures acts similarly to GaCl3; however, the
yield of pyrazoline 4a is rather low due to considerable side re-
actions (Table 1).
Table 1
Yields of compounds 4a and 5a in Lewis acid catalyzed reactions of cyclopropane 1a
with pyrazolines 2a and 3a (reagent ratios: 1a:2a¼1.2:1, 1a:3a 1:1; solvent: CH2Cl2)
Pyrazoline
Lewis acid
mol %
T (ꢀC)
t
Isolated yield (%)
Formally, the observed formation of substituted pyrazoline 4a
corresponds to the addition of the 1,3-dipolar intermediate (formed
due to the cyclopropane ring opening) to the NeH bond in 2-pyr-
azoline 3a. However, in reality, the reaction of cyclopropane 1a with
pre-synthesized 2-pyrazoline 3a in the presence of GaCl3 is more
complicated than in the case of 1-pyrazoline 2a. In fact, the use of
equimolar amounts of 1a, 3a, and GaCl3 yields a complex mixture of
compounds, in which the content of pyrazoline 4a does not exceed
20%. Furthermore, we have shown in a special experiment that in
the absence of cyclopropane 1a, noticeable isomerization of 2a to
3a in the presence of an equimolar amount of GaCl3 requires a few
hours, whereas the reaction of cyclopropane 1a with pyrazolines is
complete within 5 min.
4aa
5aa
2a
2a
3a
2a
3a
2a
2a
2a
2a
2a
2a
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Yb(OTf)3
Yb(OTf)3
In(OTf)3
GaCl3
GaCl3
GaCl3
EtAlCl2
EtAlCl2
5
1
5
5
5
20
20
20
20
20
20
0e5
20
0e5
20
12 h
72 h
12 h
72 h
72 h
72 h
5 min
5 min
5 min
5 min
20 min
61
60
31
55
30
19
18
59
72
0
29
26
61
27
54
10
0
0
0
0
0
5
20
100
100
100
100
ꢁ60
32
a
Compounds 4a and 5a are formed as a mixture of diastereomers in about 1:1
ratio.

Y.V. Tomilov et al. / Tetrahedron 66 (2010) 9151e9158
9153
Based on the above results and the literature data1,6,14 con-
cerning three-membered ring opening in cyclopropane-1,1-dicar-
boxylates, a likely reaction mechanism can be suggested. The main
Unlike compounds 1a and 1b, cyclopropanedicarboxylate 1c is
much less reactive: its reaction with pyrazoline 2a requires the
presence of GaCl3. As expected, substituted pyrazoline 4c is the only
1:1 product that was isolated (Scheme 3, Table 2).
contribution of Lewis acids probably involves activation of a s-CeC
bond in the cyclopropane ring, which is favored by coordination of
the Lewis acid to the ester oxygen atoms. Electron-donating groups
(EDG) at C(2) in the cyclopropane stabilize dipolar intermediate 6,
which then reacts with pyrazolines 2a or 3a (Scheme 4).
The presence of just one ester group at the cyclopropane ring
(even if a vicinal electron-donating substituent is present) can also
affect its reactivity to a considerable extent. In fact, the E-isomer
of methyl 2-ethoxycyclopropanecarboxylate does not react with
OMe
R1
R2
EDG
R1
O
R2
N
N
2
MLn
N
NH
3
MeO
O
MLn
6
(M = Sc, Yb)
3
R1
R2
CO2Me
CO2Me
Ln
EDG
M
1
O
O
N
N
OMe
6
OMe
O
MLn
R1
R2
MeO
EDG
MeO
(M = Sc, Yb)
N
N
H
O
MLn
EDG
7
4
5
8
H+ (M = Ga)
Scheme 4.
In the case of 1-pyrazoline, intermediate 6 attacks the nucle-
ophilic nitrogen atom with simultaneous or subsequent proton
elimination from the CH2 group to give intermediate 7, which
adds a proton to the carbon atom bound to two ester groups, thus
regenerating the catalyst (M¼Sc, Yb, In) and giving N-substituted
pyrazolines 4 or their stable complexes in the case of GaCl3; the
latter effect makes it necessary to use an equimolar amount of
gallium trichloride, so pyrazolines 4 can only be isolated by acidic
treatment of the reaction mixture. Cyclopropane 1a and pyrazo-
line 3a in the presence of GaCl3 undergo deeper conversions, as it
is in fact observed if compound 3a is used as the starting
substrate.
In the case of Sc, Yb, and In triflates, cyclopropane 1a reacts with
pyrazolines 2a and 3a much more slowly than in the presence of
GaCl3, and a considerable fraction of 1-pyrazoline undergoes isom-
erization to 2-pyrazoline under these conditions. As a result, in-
termediate 7 can be formed both from 1-pyrazolines 2 and from
2-pyrazolines 3. Although the basic properties of the NH group in
pyrazoline 3 are weak, activated cyclopropane 6 can attack it to give
intermediate 7. A similar addition of amines to donoreacceptor cy-
clopropanes has been described elsewhere.24 Yet, pyrazoline 3
predominantly reacts with cyclopropane 1 in a different way. Ap-
parently, electrophilic intermediate 6 can attack the imine nitrogen
atom to give intermediate 8, which undergoes cyclization to bicyclic
pyrazoline 5 (Scheme 4). At least, this mechanism explains both the
formation of a mixture of compounds 4 and 5 if Sc, Yb, or In are used,
and the predominant formationof eachof them dependingonwhich
of the starting pyrazolines 2 or 3 is used in the reaction.
pyrazoline 2a even in the presence of GaCl3, whereas the Z-isomer
undergoes reactions resulting in a complex mixture of various
compounds.
Geminal phenyl substituents in pyrazolines 2b and 3b consid-
erably shield the nitrogen atom, which is nearest to them and
hence the attack of cyclopropane 1a on the N atom is hindered
significantly. In both cases, diazabicyclooctane 5d is the major
product of the reaction of cyclopropane 1a with pyrazolines 2b and
3b; it is formed according to Scheme 4 due to attack of intermediate
6 on the N(2) atom in 2-pyrazoline 3b. In the case of 1-pyrazoline
2b, the formation of diazabicyclooctane 5d is apparently preceded
by its isomerization to 2-pyrazoline 3b, whereas the fraction of
substituted pyrazoline 4d is as low as about 5% due to steric hin-
drance (Scheme 5, Table 2).
Reactions of cyclopropanedicarboxylate 1a with polycyclic pyr-
azolines 2c and 3c or with 3,5-disubstituted 2-pyrazoline 3d, both
in the presence of GaCl3 and Sc(OTf)3, give only ‘open’ structures,
namely N-substituted 2-pyrazolines 4eeg. The absence of dia-
zabicyclooctanes in the case of 2-pyrazolines 3c,d is apparently due
to the presence of an electron-withdrawing substituent at the C]N
bond, which makes the formation of an 8 type intermediate im-
possible; as a result, the selectivity of the formation of N-
substituted 2-pyrazolines 4 increases significantly.
R
CO2Me
Ph
N
N
CO2Me
MeO2C
MeO2C
N
N
We have then studied the reactions of 2-phenylcyclopropan-1,1-
dicarboxylate 1a with other 1- and 2-pyrazolines and the reactions
of pyrazolines 2a and 3a with 2-thienyl- (1b) and unsubstituted
(1c) dimethyl cyclopropane-1,1-dicarboxylates.
CO2Me
CO2Me
Ph
4e,f: R = H (e); CO2Me (f)
4g
2-Thienylcyclopropanedicarboxylate 1b reacts with pyrazolines
2a or 3a similarly to cyclopropane 1a to predominantly give
substituted pyrazoline 4b in the presence of GaCl3 or, depending on
the pyrazoline nature, either mostly the same compound 4b or 1,2-
diazabicyclo[3.3.0]octane 5b in the presence of Sc(OTf)3 (Scheme 3,
Table 2). Based on 1H and 13C NMR spectra, both compounds are
mixtures of diastereomers formed in a about 1:1 ratio.
As expected, incorporation of an electron-withdrawing sub-
stituent at position 1 of 2-pyrazoline 3e drastically decreases the
reactivity of the C]N bond; however, even in this case the 1,2-
diazabicyclo[3.3.0]octane structure can be formed. In fact, it is
only in boiling dichloroethane that the reaction of cyclopropane
1a with benzoylated pyrazoline 3e in the presence of 10 mol %

9154
Y.V. Tomilov et al. / Tetrahedron 66 (2010) 9151e9158
Table 2
Reaction of cyclopropane-1,1-dicarboxylates 1aec with pyrazolines 2 and 3 in the presence of Lewis acids in CH2Cl2 as the solvent
Cyclopropane
Pyrazoline
Lewis acid
Molar ratio
Temperature (ꢀC)
Time
Products obtained
(ratio of isomers)
Yields (%)
4
5
CO2Me
Me
2a
2a
GaCl3
Sc(OTf)3
1.2:1:1
1.2:1:0.05
5
20
15 min
9 h
4b (1:1)
4b (1:1) and 5b (1:1)
72
66
d
1b
1b
18
N
N
N
CO2Me
Me
3a
2a
2b
3b
2c
Sc(OTf)3
GaCl3
1:1:0.05
1.2:1:1
20
20
20
20
10
3 h
4b (1:1) and 5b (1:1)
28
79
5
57
d
63
82
d
NH
N
CO2Me
Me
1c
1a
1a
1a
1a
3 h
4c
N
Ph
Ph
Sc(OTf)3
Sc(OTf)3
GaCl3
1.2:1:0.05
1:1:0.05
1.2:1:1
160 h
24 h
5 min
4d and 5d
N
N
Ph
Ph
5d
d
60
N
NH
4e (1.5:1)
N
N
CO2Me
3c
3c
GaCl3
Sc(OTf)3
1.2:1:1
1:1:0.05
10
20
5 min
12 h
4f (2:1)
4f (2:1)
85
95
N
N
H
CO2Me
HN
1a
3d
Sc(OTf)3
Sc(OTf)3
1:1:0.05
20
3 h
4g (1.8:1)
5e (1:1)
96
CO2Me
N
CO2Me
Me
22a
N
N
1a
3e
3:1:0.1
80, (ClCH2)2
12 h
COPh
a
Conversion of 3e is about 25% under full consumption of cyclopropane 1a; ratio of diastereomers was estimated from the 1H NMR spectrum.
Ph
Ph
Ph
CO2Me
Ph
N
MeO2C
CO2Me
N
N
N
N
Ph
Ph
MeO2C
2b
Sc(OTf)3
CH2Cl2
+
or
+
N
N
Ph
Ph
Ph
Ph
1a
Ph
H
MeO2C
CO2Me
NH
3b
5d
4d
Scheme 5.
CO2Me
Me
CO2Me
Sc(OTf)3 occurs to a noticeable extent; the conversion of 3e to
diazabicyclooctane 5e is as low as 25% even after a period of 12 h
(Table 2). The same product 5e is selectively formed as anti- or
syn-stereoisomers upon benzoylation of individual dia-
zabicyclooctanes of anti- and syn-5a with benzoyl chloride in
pyridine (Scheme 6).
BzCl, Py
96%
Me
N
NH
N N
COPh
3a
3e
22% 1a, Sc(OTf)3
61% 1a, Sc(OTf)3
As one can see from Scheme 4, the reactions of donoreacceptor
cyclopropanes 1 with 1-pyrazolines 2 along any of these two di-
CO2Me
CO2Me
MeO2C
MeO2C
rections requires the presence of an
could be expected that a 1-pyrazoline in which the
a
-proton at the N]N bond. It
-protons are
CO2Me
Me
CO2Me
Me
a
BzCl, Py
92–94%
N
substituted and hence its isomerization to a 2-pyrazoline is im-
possible, would react with a donoreacceptor cyclopropane at the
N]N bond. However, unlike aryl-substituted azo compounds and
azodicarboxylates,13,14 we failed to observe a similar reaction of
dimethyl 3,5-dimethyl-1-pyrazoline-3,5-dicarboxylate. Even under
N
N
N
Ph
Ph
H
COPh
5a
5e
Scheme 6.

Y.V. Tomilov et al. / Tetrahedron 66 (2010) 9151e9158
9155
drastic reaction conditions (Sc(OTf)3, toluene, 110 ꢀC, 24 h), cyclo-
propane 1a did not give products of addition of this 1-pyrazoline to
the N]N bond.
column chromatography on silica gel to afford N-substituted 2-
pyrazolines 4 and 1,2-diazabicyclo[3.3.0]octanes 5.
4.2.1. Dimethyl 2-[2-(4,5-dihydro-5-methoxycarbonyl-5-methyl-1H-
3. Conclusion
pyrazol-1-yl)-2-phenylethyl]malonate (4a).
In summary, we report the first study of the reactions of 2-
substituted cyclopropane-1,1-dicarboxylates with 1- and 2-pyr-
azolines of various structures in the presence of Lewis acids (mainly
Sc(OTf)3 and GaCl3). We have shown that, depending on the re-
action conditions, the Lewis acid used, and the type of substituents
in the starting pyrazolines, the reaction mostly occurs along two
directions to predominantly give N-substituted 2-pyrazolines 4 or
1,2-diazabicyclo[3.3.0]octanes 5. A Lewis acid present in the system
activates the opening of the cyclopropane ring and addition of the
electrophilic intermediate formed to the nitrogen atoms of the
pyrazoline ring followed by proton migration from the ring CH-
fragment to an electronegative C atom or cyclization at the C]N
bond of 2-pyrazoline. Furthermore, Sc(OTf)3 and Yb(OTf)3 can be
used in 5 mol %. Thus, we have suggested a new method for syn-
thesizing mono- and bicyclic nitrogen-containing heterocycles,
including such compounds that are hard to obtain by other
methods. These compounds contain various functional groups that
can subsequently be modified.
4.2.1.1. Method A. The residue from reaction of 1a (338 mg,
1.44 mmol) and 2a (170 mg, 1.2 mmol) in the presence of GaCl3
(211 mg, 1.2 mmol) was purified by column chromatography
(benzeneeEtOAc, 8:1) to give 4a (325 mg, 72%) as a colorless oil
(about 1:1 mixture of two diastereomers). IR (CHCl3) 1732 br (C]
O), 1587, 1493, 1455, 1437 cmꢁ1; MS (m/z, %): 376 (4, Mþ), 345 (5,
MþꢁOCH3); 317 (24, MþꢁCO2CH3), 285 (5), 235 (74), 231 (25), 203
(24), 175 (44), 171 (50), 143 (36), 115 (100), 104 (32), 83 (45), 77 (15),
59 (13). Anal. Calcd for C19H24N2O6: C, 60.63; H, 6.43; N, 7.44.
Found: C, 60.60; H, 6.49; N, 6.96. The product obtained (12 mg) was
additionally separated by Silufol chromatographic plate
(20ꢂ20 cm) eluting with benzeneeEtOAc, 10:1 to afford the pure
isomers. S
*
,R d
-4a: 1H NMR 1.43 (s, 3H, CH3), 2.39 (ddd, 1H, Ha(10),
*
2J¼13.9, 3J¼8.7 and 6.2 Hz), 2.64 (dd, 1H, Ha(400), 2J¼17.3, 3J¼1.8 Hz),
2.76 (ddd, 1H, Hb(10), 2J¼13.9, 3J¼9.6 and 6.1 Hz), 2.92 (s, 3H, OCH3),
3.28 (dd, 1H, Hb(400), 2J¼17.3, 3J¼1.8 Hz), 3.54 (dd, 1H, H(2), 3J¼8.7
and 6.1 Hz), 3.71 and 3.73 (all s, 2ꢂ3H, 2OCH3), 4.18 (dd, 1H, H(20),
3J¼9.6 and 6.2 Hz), 6.55 (br.t, 1H, HC¼, 3J¼1.8 Hz), 7.19e7.34 (m, 5H,
C6H5); 13C NMR 21.3 (CH3), 36.4 (H2C(10)), 46.3 (H2C(400)), 49.2 (HC
d
4. Experimental section
4.1. General
(2)), 51.4, 52.4 and 52.5 (3OCH3), 59.0 (HC(20)), 67.4 (C(500)), 127.3
(p-C), 127.9 and 128.1 (2 o-C and 2 m-C), 136.4 (HC]), 141.1 (i-C),
169.8, 170.2 and 173.8 (3COO). R
*
,R d 0.96 (s, 3H, CH3),
-4a: 1H NMR
*
2.34 (ddd, 1H, Ha(10), 2J¼14.0, 3J¼9.3 and 5.0 Hz), 2.54 (dd, 1H,
3
All reagents and solvents used were commercial grade
chemicals. Cyclopropanes 1a and 1b were obtained using the
CoryeChaikovsky reaction;25e27 cyclopropane 1c was prepared
using a procedure reported previously.28,29 Pyrazolines 2aec and
3aed were synthesized on the dipolar cycloaddition reaction of
diazo compounds to alkenes as described early for 2a,30,31 2b,32
2c,33 3a,34 3b,35 3c,36 3d.37,38 The following Lewis acids were
used in the study: Sc(OTf)3 from Acros Organics, as well as EtAlCl2
(0.8 M solution in hexane), GaCl3, Yb(OTf)3, and In(OTf)3 from
Aldrich. TLC analysis was performed on Silufol chromatographic
plates (Merck). For preparative chromatography, silica gel 60
(0.040e0.063 mm; Merck) was used. 1H and 13C NMR spectra were
recorded on a Bruker AMX-400 spectrometer (400 and 100.7 MHz,
respectively) in CDCl3 containing 0.05% Me4Si as the internal
standard. Assignments of 1H and 13C signals were made with the
aid of 2D COSY, NOESY, HSQC, and HMBC spectra where necessary.
IR spectra were obtained using a Specord M80-2 or Bruker ALPHA-
T spectrometers as potassium bromide disks or in CHCl3 solution.
Mass spectra were recorded on a Finnigan MAT INCOS-50 in-
strument (EI, 70 eV, direct inlet probe). High resolution mass
spectra were obtained on a micrOTOF instrument. The elemental
compositions were determined on a PerkineElmer Series II 2400
CHN Analyzer.
Ha(400), 2J¼17.5, J¼1.8 Hz), 2.72 (ddd, 1H, Hb(10), 2J¼14.0, 3J¼10.2
and 5.0 Hz), 3.30 (dd, 1H, Hb(400), 2J¼17.5, 3J¼1.8 Hz), 3.73 (dd, 1H, H
(2), 3J¼9.3 and 5.0 Hz), 3.69, 3.75 and 3.77 (all s, 3ꢂ3H, 3OCH3), 4.34
(dd, 1H, H(20), 3J¼10.2 and 5.0 Hz), 6.49 (br t, 1H, HC], 3J¼1.8 Hz),
7.20e7.44 (m, 5H, C6H5); 13C NMR
d
21.9 (CH3), 36.5 (H2C(10)), 46.4
(H2C(400)), 49.0 (HC(2)), 52.3, 52.4 and 52.5 (3OCH3), 60.1 (HC(20)),
69.6 (C(500)), 127.1 (p-C), 127.5 and 128.3 (2 o-C and 2 m-C), 134.8
(HC]), 144.2 (i-C), 169.7, 169.9 and 172.4 (3COO).
4.2.1.2. Method B. The residue from reaction of 1a (337 mg,
1.45 mmol) and 2a (170 mg, 1.2 mmol) in the presence of Sc(OTf)3
(29 mg, 0.06 mmol) was separated by column chromatography
(benzeneeEtOAc, 8:1) to give 4a (275 mg, 61%), which was identical
to the sample prepared above and anti- and syn-5a (summary yield
131 mg, 29%), which 1H and 13C NMR spectra are the same as de-
scribed below.
4.2.2. Trimethyl 3-methyl-8-phenyl-1,2-diazabicyclo[3.3.0]octane-
3,6,6-tricarboxylate (5a). The residue from reaction of 1a (281 mg,
1.2 mmol) and 3a (171 mg, 1.2 mmol) in the presence of Sc(OTf)3
(30 mg, 0.06 mmol) was separated by column chromatography
(benzeneeEtOAc, 10:1 to 1:1) to give 4a (140 mg, 31%), which was
identical to the sample prepared above and anti-5a (138 mg, 31%)
and syn-5a (135 mg, 30%). anti-5a: Colorless thick oil; IR (CHCl3)
3320 br (NH), 1735 br (C]O), 1700, 1601, 1494, 1450, 1436 cmꢁ1; 1H
4.2. General procedure for reactions of donoreacceptor
cyclopropanes with pyrazolines in the presence of Lewis acids
NMR
d
1.52 (s, 3H, CH3), 1.96 (dd, 1H, Ha(4), 2J¼13.2, 3J¼12.4 Hz),
2.00 (dd, 1H, Ha(7), 2J¼13.6, 3J¼10.6 Hz), 2.55 (dd, 1H, Hb(4),
2J¼13.2, 3J¼6.0 Hz), 3.09 (dd, 1H, Hb(7), 2J¼13.6, 3J¼7.0 Hz), 3.72,
3.76 and 3.78 (all s, 3ꢂ3H, 3OCH3), 4.10 (dd, 1H, H(8), 3J¼10.6 and
7.0 Hz), 4.39 (dd, 1H, H(5), 3J¼12.4 and 6.0 Hz), 5.09 (br s, 1H, NH),
7.22 (br t, 1H, p-CH, 3J¼7.6 Hz), 7.31 (br dd, 2H, 2 m-CH, 3J¼7.5 and
To a solution of cyclopropane 1 (1.45 mmol) and pyrazoline 2
(1.2 mmol) or cyclopropane 1 (1.2 mmol) and pyrazoline 3
(1.2 mmol) in 5 mL of dichloromethane was added Sc(OTf)3
(0.06 mmol) in one portion or solution of GaCl3 (1.2 mmol) in 1 mL
of dichloromethane and reaction mixture was stirred at a temper-
ature and during a time indicated in Tables 1 or 2. After that
aqueous solution of HCl (5%) was added at 0 ꢀC until pH 3 was
achieved and the reaction mixture was extracted with dichloro-
methane (3ꢂ8 mL). The organic layer was dried over MgSO4 and
the solvent was removed in vacuo. The residue was separated by
7.6 Hz), 7.39 (br t, 1H, o-CH, 3J¼7.5 Hz); 13C NMR
d 27.9 (CH3), 41.0 (C
(4)), 41.2 (C(7)), 52.8, 52.9 and 53.1 (3OCH3), 58.9 (C(6)), 67.9 (C(5)),
69.0 (C(3)), 70.0 (C(8)),127.3 (2 o-C), 127.4 (p-C),128.4 (2 m-C), 141.0
(i-C), 170.3, 171.1 and 176.4 (3COO); MS (m/z, %): 376 (34, Mþ), 345
(3, MþꢁOCH3), 317 (42, MþꢁCO2CH3), 283 (5), 255 (10), 203 (13),
171 (94), 146 (32), 143 (39), 121 (28), 115 (55), 104 (41), 91 (28), 83

9156
Y.V. Tomilov et al. / Tetrahedron 66 (2010) 9151e9158
(100), 59 (22). Anal. Calcd for C19H24N2O6: C, 60.63; H, 6.43; N, 7.44.
chromatography (benzeneeEtOAc, 10:1 to 1:1) to give R
*
,R
*
-4b
Found: C, 60.48; H, 6.48; N, 7.38. syn-5a: Colorless thick oil; 1H NMR
(67 mg, 15%) and S ,R -4b (59 mg, 13%), which were identical to the
*
*
d
1.45 (s, 3H, CH3), 2.03 (dd,1H, Ha(7), 2J¼13.7, 3J¼10.4 Hz), 2.05 (dd,
samples prepared above, and anti-5b (133 mg, 29%) and syn-5b
(129 mg, 28%). anti-5b: Colorless thick oil; IR (CHCl3) 3360 br (NH),
1H, Ha(4), 2J¼12.9, 3J¼6.9 Hz), 2.55 (dd, 1H, Hb(4), 2J¼12.9,
3J¼11.3 Hz), 3.13 (dd, 1H, Hb(7), 2J¼13.7, 3J¼7.4 Hz), 3.73, 3.75 and
3.78 (all s, 3ꢂ3H, 3OCH3), 4.06 (br s, 1H, NH), 4.18 (dd, 1H, H(8),
3J¼10.4 and 7.4 Hz), 4.49 (dd, 1H, H(5), 3J¼11.3 and 6.9 Hz), 7.22 (br
t, 1H, p-CH, 3J¼7.3 Hz), 7.30 (br dd, 2H, 2 m-CH, 3J¼7.3 and 7.7 Hz),
1732 br (C]O), 1700, 1684, 1651, 1520, 1456, 1436 cmꢁ1 1H NMR
;
d
1.52 (s, 3H, CH3), 1.88 (dd, 1H, Ha(4), 2J¼12.7, 3J¼12.4 Hz), 2.15 (dd,
1H, Ha(7), 2J¼13.6, 3J¼10.3 Hz), 2.55 (dd, 1H, Hb(4), 2J¼12.7,
3J¼6.2 Hz), 3.12 (dd, 1H, Hb(7), 2J¼13.6, 3J¼6.9 Hz), 3.72, 3.77 and
3.78 (all s, 3ꢂ3H, 3OCH3), 4.35 (dd, 1H, H(8), 3J¼10.3 and 6.9 Hz),
4.39 (dd, 1H, H(5), 3J¼12.4 and 6.2 Hz), 5.18 (br s, 1H, NH), 6.93 (dd,
1H, Hthi(4), 3J¼5.0 and 3.4), 6.95 (dd, 1H, Hthi(3), 3J¼3.4, 4J¼1.4), 7.19
7.37 (br t, 1H, o-CH, 3J¼7.7 Hz); 13C NMR
d 25.1 (CH3), 40.2 (C(7)),
40.9 (C(4)), 52.6, 52.9 and 53.2 (3OCH3), 59.2 (C(6)), 67.3 (C(8)), 68.3
(C(3)), 69.0 (C(5)), 127.4 (p-C), 127.5 (2 o-C), 128.5 (2 m-C), 141.6 (i-
C), 170.0, 171.4 and 176.3 (3COO); MS (m/z, %): 376 (58, Mþ), 345 (5,
MþꢁOCH3), 317 (42, MþꢁCO2CH3), 283 (2), 255 (11), 203 (16), 171
(93), 146 (52),143 (41),121 (41),115 (66),104 (56), 91 (32), 83 (100),
59 (22), 44 (46), 32 (86). Anal. Calcd for C19H24N2O6: C, 60.63; H,
6.43; N, 7.44. Found: C, 60.41; H, 6.50; N, 7.33.
(dd, 1H, Hthi(5), 3J¼5.0, 4J¼1.4); 13C NMR
d 27.7 (CH3), 40.8 (C(4)),
41.0 (C(7)), 52.9, 53.0 and 53.2 (3OCH3), 59.1 (C(6)), 66.2 (C(8)), 67.8
(C(5)), 69.0 (C(3)), 124.2 (Cthi(3)), 124.5 (Cthi(5)), 126.7 (Cthi(4)),
146.2 (Cthi(2)), 170.1, 170.8 and 176.2 (3COO); MS (m/z, %): 382 (18,
Mþ), 351 (1, MþꢁOCH3), 323 (14, MþꢁCO2CH3), 261 (2), 240 (11),
208 (28), 177 (47), 149 (19), 121 (33), 97 (30), 83 (100), 59 (19). Anal.
Calcd for C17H22N2SO6: C, 53.39; H, 5.80; N, 7.33. Found: C, 53.28; H,
5.58; N, 7.17. syn -5b: Colorless thick oil; IR (CHCl3) 3370 br (NH),
4.2.3. Dimethyl 2-[2-(4,5-dihydro-5-methoxycarbonyl-5-methyl-1H-
pyrazol-1-yl)-2-(2-thienyl)ethyl]malonate (4b).
1732 br (C]O), 1699, 1682, 1650, 1520, 1455, 1435 cmꢁ1 1H NMR
;
4.2.3.1. Method A. The residue from reaction of 1b (348 mg,
1.45 mmol) and 2a (170 mg, 1.2 mmol) in the presence of GaCl3
(210 mg, 1.2 mmol) was purified by column chromatography (ben-
d
1.47 (s, 3H, CH3), 2.03 (dd, 1H, Ha(4), 2J¼12.8, 3J¼7.0 Hz), 2.17 (dd,
1H, Ha(7), 2J¼13.7, 3J¼9.9 Hz), 2.49 (dd, 1H, Hb(4), 2J¼12.8,
3J¼11.2 Hz), 3.16 (dd, 1H, Hb(7), 2J¼13.7, 3J¼7.4 Hz), 3.73, 3.75 and
3.78 (all s, 3ꢂ3H, 3OCH3), 4.02 (br s, 1H, NH), 4.49 (m, 2H, H(5) and
H(8)), 6.92 (dd, 1H, Hthi(4), 3J¼4.9 and 3.5), 6.94 (dd, 1H, Hthi(3),
zeneeEtOAc, 5:1) giving diastereomers R
*
,R -4b (170 mg, 37%) and
*
S
*
,R -4b (161 mg, 35%). R ,R -4b: Colorless thick oil; IR (CHCl3) 1733
*
*
*
br (C]O), 1585, 1510, 1455, 1436 cmꢁ1; H NMR
d
1.15 (s, 3H, CH3),
3J¼3.5, 4J¼1.4), 7.18 (dd, 1H, Hthi(5), 3J¼4.9, 4J¼1.4); 13C NMR
d 25.0
1
2.41 (ddd,1H, Ha(10), 2J¼13.8, 3J¼8.9 and 5.0 Hz), 2.55 (dd,1H, Ha(400),
(CH3), 40.2 (C(7)), 40.9 (C(4)), 52.7, 53.0 and 53.2 (3OCH3), 59.3 (C
(6)), 63.5 (C(8)), 68.3 (C(3)), 68.9 (C(5)), 124.6 (Cthi(5)), 124.7
(Cthi(3)), 126.7 (Cthi(4)), 146.3 (Cthi(2)), 169.9, 171.0 and 176.2
(3COO); MS (m/z, %): 382 (21, Mþ), 351 (1, MþꢁOCH3), 323 (9,
MþꢁCO2CH3), 261 (3), 240 (11), 208 (45), 177 (41), 149 (20), 121
(38), 97 (32), 83 (100), 59 (20). HRMS calcd for C17H22N2SO6: MþH,
383.1271; MþNa, 405.1091. Found: m/z 383.1269, 405.1089.
2J¼17.4, J¼1.4 Hz), 2.71 (ddd, 1H, Hb(10), 2J¼13.8, 3J¼10.3 and
3
5.2 Hz), 3.32 (dd, 1H, Hb(400), 2J¼17.4, 3J¼1.1 Hz), 3.70, 3.77 and 3.78
(all s, 3ꢂ3H, 3OCH3), 3.75 (dd, 1H, H(2), 3J¼8.9 and 5.2 Hz), 4.80 (dd,
1H, H(20), 3J¼10.3 and 5.0 Hz), 6.65 (br dd, 1H, HC¼, 3J¼1.4 and
1.1 Hz), 6.89 (dd, 1H, Hthi(4), 3J¼5.1 and 3.4), 6.97 (dd, 1H, Hthi(3),
3J¼3.4, J¼0.9), 7.16 (dd, 1H, Hthi(5), 3J¼5.1, 4J¼0.9); 13C NMR
d 22.0
4
(CH3), 37.7 (H2C(10)), 46.0 (H2C(400)), 49.1 (HC(2)), 51.6, 52.5 and 52.6
(3OCH3), 55.1 (HC(20)), 67.4 (C(500)), 125.3 (Cthi(5)), 125.6 (Cthi(4)),
126.1 (Cthi(3)), 138.6 (HC]), 143.3 (Cthi(2)), 169.7, 169.8 and 172.1
(3COO); MS (m/z, %): 382 (3, Mþ), 351 (5, MþꢁOCH3), 323 (17,
MþꢁCO2CH3), 241 (98), 237 (41), 209 (26), 181 (97), 177 (73), 121
4.2.5. Dimethyl 2-[2-(4,5-dihydro-5-methoxycarbonyl-5-methyl-1H-
pyrazol-1-yl)ethyl]malonate (4c). The residue from reaction of 1c
(228 mg, 1.44 mmol) and 2a (170 mg, 1.2 mmol) in the presence of
GaCl3 (209 mg, 1.2 mmol) was purified by column chromatography
(benzeneeEtOAc, 5:1) to give 4c (285 mg, 79%) as a colorless thick
(100), 110 (49), 83 (76). S
*
*
,R -4b: Colorless thick oil; NMR d 1.48 (s,
3H, CH3), 2.44 (ddd, 1H, Ha(10), 2J¼13.9, 3J¼8.6 and 6.0 Hz), 2.65 (dd,
1H, Ha(400), 2J¼17.3, 3J¼1.4 Hz), 2.71 (ddd, 1H, Hb(10), 2J¼13.9, 3J¼9.5
and 6.1 Hz), 3.10 (s, 1H, OCH3), 3.27 (dd, 1H, Hb(400), 2J¼17.3,
3J¼1.7 Hz), 3.59 (dd, 1H, H(2), 3J¼8.6 and 6.1 Hz), 3.72 and 3.75 (all s,
2ꢂ3H, 2OCH3), 4.57 (dd,1H, H(20), 3J¼9.5 and 6.0 Hz), 6.67 (br dd,1H,
HC], 3J¼1.7 and 1.4 Hz), 6.83 (dd, 1H, Hthi(3), 3J¼3.4, 4J¼1.2), 6.87
(dd, 1H, Hthi(4), 3J¼5.1 and 3.4), 7.17 (dd, 1H, Hthi(5), 3J¼5.1, 4J¼1.2);
oil; 1H NMR
d
1.31 (s, 3H, CH3), 2.32 (m, 2H, H2C(10)), 2.61 (dd, 1H,
3
Ha(400), 2J¼17.0, J¼1.8 Hz), 3.04 (m, 2H, H2C(20)), 3.23 (dd, 1H,
Hb(400), 2J¼17.0, 3J¼1.7 Hz), 3.72, 3.73 and 3.74 (all s, 3ꢂ3H, 3OCH3),
3.76 (dd, 1H, H(2), 3J¼7.8 and 7.0 Hz), 6.64 (br dd, 1H, HC], 3J¼1.8
and 1.7 Hz); 13C NMR
d
18.8 (CH3), 28.2 (H2C(10)), 46.1 (H2C(400)),
46.2 (HC(20)), 48.8 (HC(2)), 52.2 (OCH3), 52.4 (2OCH3), 69.9 (C(500)),
139.3 (HC]), 170.0 (2COO), 173.3 (COO); MS (m/z, %): 300 (2) [Mþ],
269 (3, MþꢁOCH3), 241 (28, MþꢁCO2CH3), 237 (9), 209 (23), 177
(100),159 (11),127 (11), 95 (14), 59 (13). Anal. Calcd for C13H20N2O6:
C, 51.99; H, 6.71; N, 9.33. Found: C, 51.75; H, 6.98; N, 9.09.
13C NMR
d
20.9 (CH3), 37.9 (H2C(10)), 46.2 (H2C(400)), 48.9 (HC(2)),
52.4, 52.5 and 52.6 (3OCH3), 56.1 (HC(20)), 70.1 (C(500)),124.8 (Cthi(5)),
125.2 (Cthi(3)),126.0 (Cthi(4)),137.2 (HC]),146.2 (Cthi(2)),169.8,170.1
and 173.6 (3COO); MS (m/z, %): 382 (2, Mþ), 351 (3, MþꢁOCH3), 323
(8, MþꢁCO2CH3), 241 (41), 237 (17), 209 (12), 181 (41), 177 (34), 121
(51), 110 (23), 83 (38), 44 (65), 32 (100). Anal. Calcd for C17H22N2SO6:
C, 53.39; H, 5.80; N, 7.33. Found: C, 53.01; H, 5.91; N, 7.02.
4.2.6. Dimethyl 3,3,8-triphenyl-1,2-diazabicyclo[3.3.0]octane-6,6-di-
carboxylate (5d).
4.2.6.1. Method A. The residue from reaction of 1a (280 mg,
1.2 mmol) and 3b (267 mg, 1.2 mmol) in the presence of Sc(OTf)3
(30 mg, 0.06 mmol) was purified by column chromatography
(benzeneeEtOAc, 2:1) to give 5d (450 mg, 82%) as a colorless thick
oil; IR (CHCl3) 3370 br (NH), 1736 br (C]O), 1686, 1600, 1492,
4.2.3.2. Method B. The residue from reaction of 1b (347 mg,
1.44 mmol) and 2a (171 mg, 1.2 mmol) in the presence of Sc(OTf)3
(29 mg, 0.06 mmol) was separated by column chromatography
(benzeneeEtOAc, 10:1 to 1:1) to give R
*
*
,R -4b (153 mg, 33%) and
S
*
*
,R -4b (0.150 mg, 33%), which were identical to the samples
1448 cmꢁ1
;
1H NMR
d
2.27 (ddd, 1H, Ha(10), 2J¼13.9, 3J¼9.6 and
prepared above, and anti-5b (42 mg, 9%) and syn-5b (40 mg, 9%),
which properties are the same as described below.
4.9 Hz), 2.63 (ddd, 1H, Hb(10), 2J¼13.9, 3J¼10.3 and 5.2 Hz), 2.93 (dd,
1H, H(2), 3J¼9.6 and 5.2 Hz), 3.40 (dd,1H, Ha(400), 2J¼18.0, 3J¼1.8 Hz),
3.47 (dd,1H, Hb(400), 2J¼18.0, 3J¼1.7 Hz), 3.53 and 3.62 (both s, 2ꢂ3H,
2OCH3), 4.02 (dd, 1H, H(2), 3J¼10.3 and 4.9 Hz), 4.50 (br s, 1H, NH),
6.68 (dd, 1H, HC], 3J¼1.8 and 1.7 Hz), 6.87e7.50 (m, 15H, 3C6H5);
4.2.4. Trimethyl
3-methyl-8(2-thienyl)-1,2-diazabicyclo[3.3.0]oc-
tane-3,6,6-tricarboxylate (5b). The residue from reaction of 1b
(288 mg, 1.2 mmol) and 3a (172 mg, 1.2 mmol) in the presence of Sc
(OTf)3 (30 mg, 0.06 mmol) was separated by column
13C NMR
d 40.9 (C(7)), 44.0 (C(4)), 53.0 and 53.2 (2OCH3), 59.6 (C(6)),
67.4 (C(8)), 70.8 (C(5)), 74.8 (C(3)),126.2,127.1,127.7,128.0,128.4 and

Y.V. Tomilov et al. / Tetrahedron 66 (2010) 9151e9158
9157
3
128.8 (3 o-C and 3 m-C), 126.5, 127.2 and 127.3 (3 p-C), 142.3, 147.3
and 149.8 (3 i-C), 170.3 and 171.5 (2COO); MS (m/z, %): 456 (31, Mþ),
425 (2, MþꢁOCH3), 379 (5, MþꢁC6H5), 320 (4, MþꢁCO2CH3ꢁC6H5),
296 (35), 276 (15), 217 (85), 180 (99), 115 (78), 104 (100), 91 (60), 77
(82), 59 (49). Anal. Calcd for C28H28N2O4: C, 73.66; H, 6.18; N, 6.14.
Found: C, 73.47; H, 6.09; N, 6.20.
1H, Ha(10), 2J¼14.4, J¼9.5 and 5.7 Hz), 2.84 (ddd, 1H, Hb(10),
2J¼14.4, 3J¼10.0 and 5.7 Hz), 3.03 (br d, 1H, H(600), 3J¼10.5), 3.45 (br
d, 1H, H(200), 3J¼10.5), 3.61 (dd, 1H, H(2), 3J¼9.5 and 5.7 Hz), 3.72,
3.74 and 3.81 (all s, 3ꢂ3H, 3OCH3), 4.28 (dd, 1H, H(20), 3J¼10.0 and
5.7 Hz), 7.19e7.35 (m, 5H, C6H5); 13C NMR 24.2 and 28.6 (C(800) and
d
C(900)), 33.7 (C(10)), 33.8 (C(1000)), 41.3 and 42.0 (C(100) and C(700)),
49.1 (HC(2)), 51.7, 52.5 and 52.6 (3OCH3), 53.9 (C(600)), 62.3 (HC(20)),
71.3 (C(200)), 127.6 and 128.7 (2 o-C and 2 m-C), 128.0 (p-C), 139.3 (C
(500)), 139.7 (i-C), 163.7, 169.6 and 169.7 (3COO); MS (m/z, %): 428 (3,
Mþ), 397 (4, MþꢁOCH3), 369 (3, MþꢁCO2CH3), 296 (5), 283 (84),
235 (8), 175 (9), 143 (9), 115 (44), 91 (10), 44 (32), 32 (100). Anal.
Calcd for C23H28N2O6: C, 64.47; H, 6.59; N, 6.54. Found: C, 64.05; H,
4.2.6.2. Method B. The residue from reaction of 1a (336 mg,
1.44 mmol) and 2b (266 mg, 1.2 mmol) in the presence of Sc(OTf)3
(29 mg, 0.06 mmol) was separated by column chromatography
(benzeneeEtOAc, 2:1) to give 5d (345 mg, 63%), which was identical
to the sample prepared above, and a small amount of dimethyl 2-[2-
(4,5-dihydro-5,5-diphenyl-1H-pyrazol-1-yl)-2-phenylethyl]malonate
6.38; N, 6.37. R
*
,S -4f: Colorless thick oil; IR (CHCl3) 1748, 1732 and
*
4d (27 mg, 5%) as a colorless thick oil. 4d: 1H NMR
d
2.00 (dd, 1H,
1696 (C]O), 1542, 1523, 1438 cmꢁ1 1H NMR
; d 0.97e1.49 (m, 6H,
Ha(7), 2J¼13.9, 3J¼10.3 Hz), 2.41 (dd, 1H, Ha(4), 2J¼13.3, 3J¼12.0 Hz),
3.05 (dd, 1H, Hb(7), 2J¼13.9, 3J¼7.4 Hz), 3.18 (dd, 1H, Hb(4), 2J¼13.3,
3J¼6.7 Hz), 3.75 and 3.79 (both s, 2ꢂ3H, 2OCH3), 4.03 (dd, 1H, H(2),
3J¼10.3 and 7.4 Hz), 4.50 (br s, 1H, NH), 4.73 (dd, 1H, H(5), 3J¼12.0
H2C(800), H2C(900) and H2C(1000)), 2.16 and 2.50 (both m, 2ꢂ1H, H(100)
and H(700)), 2.55 (ddd, 1H, Ha(10), 2J¼14.4, 3J¼8.5 and 6.3 Hz), 2.72
(ddd, 1H, Hb(10), 2J¼14.4, J¼9.5 and 6.0 Hz), 3.10 (br d, 1H, H(600),
3
3J¼10.4), 3.50 (dd,1H, H(2), 3J¼8.5, 6.0, 9.5 Hz), 3.55 (br d,1H, H(200),
3J¼10.4), 3.72, 3.74 and 3.81 (all s, 3ꢂ3H, 3OCH3), 4.57 (dd, 1H, H
and 6.7 Hz), 7.13e7.47 (m,15H, 3C6H5); 13C NMR 35.5 (H2C(10)), 49.1
d
(H2C(400)), 49.2 (HC(2)), 52.4 and 52.5 (2OCH3), 60.5 (HC(20)), 75.7 (C
(500)), 126.6, 127.1 and 127.2 (3 p-C), 127.7, 127.8, 127.85, 127.9, 128.5
and 128.55 (3 o-C and 3 m-C),135.6(HC]),141.1,144.7 and 145.9 (3 i-
C), 169.6 and 172.4 (2COO). HRMS calcd for C28H28N2O4: MþH,
457.2122; MþNa, 479.1941. Found: m/z 457.2116, 479.1936.
(20), 3J¼9.5 and 6.3 Hz), 7.26e7.37 (m, 5H, C6H5); 13C NMR
d 24.5
and 28.0 (C(800) and C(900)), 33.1 (C(10)), 33.4 (C(1000)), 40.6 and 43.4
(C(100) and C(700)), 48.9 (HC(2)), 51.6, 52.6 and 52.65 (3OCH3), 54.2 (C
(600)), 63.4 (HC(20)), 71.5 (C(200)), 127.5 and 128.6 (2 o-C and 2 m-C),
127.9 (p-C), 138.8 (C(500)), 139.5 (i-C), 163.4, 169.4 and 169.6 (3COO);
MS (m/z, %): 428 (3, Mþ), 397 (3, MþꢁOCH3), 369 (4, MþꢁCO2CH3),
296 (7), 283 (80), 235 (9), 175 (9), 143 (10), 115 (42), 91 (10), 44 (38),
32 (100). Anal. Calcd for C23H28N2O6: C, 64.47; H, 6.59; N, 6.54.
Found: C, 64.09; H, 6.55; N, 6.29.
4.2.7. Dimethyl 2-[2-(3,4-diazatricyclo[5.2.1.02,6]dec-4-en-3-yl)-2-
phenylethyl]malonate (4e). The residue from reaction of 1a (337 mg,
1.45 mmol) and 2c (163 mg, 1.2 mmol) in the presence of GaCl3
(208 mg, 1.2 mmol) was purified by column chromatography (ben-
zeneeEtOAc, 5:1) to give diastereomeric R
,R -4e (106 mg, 24%). R ,S -4e: Colorless oil; IR (CHCl3) 1748 and
1731 (C]O), 1577, 1493, 1454, 1437 cmꢁ1; 1H NMR
0.98e1.50 (m,
*
,S
*
-4e (160 mg, 36%) and
4.2.9. Dimethyl 2-[2-phenyl-2-(3,3-bismetoxycarbonyl-4,5-dihydro-
1H-pyrazol-1-yl)ethyl]malonate (4g). The residuefromreactionof1a
(280 mg, 1.2 mmol) and 3d (224 mg, 1.2 mmol) in the presence of Sc
(OTf)3 (30 mg, 0.06 mmol) was purified by column chromatography
R
*
*
* *
d
6H, H2C(800), H2C(900) and H2C(1000)), 2.17 and 2.24 (both m, 2ꢂ1H, H
(100) and H(700)), 2.39 (ddd,1H, Ha(10), 2J¼13.9, 3J¼9.9 and 5.5 Hz), 2.68
(br d, 1H, H(600), 3J¼9.8), 2.79 (ddd, 1H, Hb(10), 2J¼13.9, 3J¼10.5 and
5.3 Hz), 3.06 (br d, 1H, H(200), 3J¼9.8), 3.72 and 3.75 (both s, 2ꢂ3H,
(benzeneeEtOAc,10:1to5:1)togivediastereomericR
*
,R -4g(313mg,
*
62%) and R ,S -4g (171 mg, 34%). R ,R -4g: Colorless crystals; mp
*
*
*
*
90e91 ꢀC; IR (KBr) 1740,1728 and 1708(C]O),1572,1540,1520,1496,
3
2OCH3), 3.83 (dd, 1H, H(2), J¼9.9 and 5.3 Hz), 3.99 (dd, 1H, H(20),
1436 cmꢁ1;1HNMR
d
2.54(ddd,1H, Ha(10), 2J¼14.1, 3J¼9.5and5.6Hz),
3J¼10.5 and5.5 Hz), 6.38 (br s,1H, H(500)), 7.21e7.33 (m, 5H, C6H5); 13C
2.96 (ddd,1H, Hb(10), 2J¼14.1, 3J¼10.0 and 5.4 Hz), 3.06 (dd,1H, Ha(400),
3
NMR
d
24.4 and 28.6 (C(800) and C(900)), 33.8 (C(1000)), 33.9 (C(10)), 40.7
2J¼17.4, J¼13.1 Hz), 3.14 (dd, 1H, Hb(400), 2J¼17.4, 3J¼12.8 Hz), 3.71
and 41.9 (C(100) and C(700)), 49.2 (HC(2)), 52.3 and 52.5 (2OCH3), 57.0
(C(600)), 63.1 (HC(20)), 67.6 (C(200)), 127.4 (p-C), 128.2 and 128.3 (2 o-C
and 2 m-C),140.3 (i-C),142.4 (C(500)),170.0 and 170.2 (2COO); MS (m/
z, %): 370 (4, Mþ), 339 (3, MþꢁOCH3), 293 (2, MþꢁC6H5), 225 (100),
175 (5),171 (8),143 (6),115 (37), 91 (8). Anal. Calcd for C21H26N2O4: C,
(dd,1H, H(2), 3J¼9.5 and 5.4 Hz), 3.72, 3.74, 3.80 and 3.82 (all s, 4ꢂ3H,
4OCH3), 3.92 (dd, 1H, H(500), 3J¼13.1 and 12.8 Hz), 4.45 (dd, 1H, H(20),
3J¼10.0 and 5.6 Hz), 7.22e7.35 (m, 5H, C6H5);13CNMR
d
33.6 (H2C(10)),
35.3 (H2C(400)), 48.8 (HC(2)), 52.0, 52.4, 52.5 and 52.6 (4OCH3), 63.2
(HC(20)), 64.7 (C(500)), 128.2 and 128.7 (2 o-C and 2 m-C), 128.3 (p-C),
137.6 and 139.0 (i-C and C(300)), 162.4, 169.5, 169.6 and 170.3 (4COO);
MS (m/z, %): 420 (2, Mþ), 389 (4, MþꢁOCH3), 361 (13, MþꢁCO2CH3),
319 (8), 288 (10), 275 (28), 235 (32), 203 (11), 175 (32), 171 (35), 143
(22),115 (100), 59(20). Anal. CalcdforC20H24N2O8:C, 57.14;H, 5.75;N,
68.09; H, 7.07; N, 7.56. Found: C, 67.63; H, 7.18; N, 7.27. R
*
,R -4e
*
Colorless oil; 1H NMR 0.91e1.46 (m, 6H, H2C(800), H2C(900) and H2C
d
(1000)), 2.01 and 2.22 (both m, 2ꢂ1H, H(100) and H(700)), 2.47 (ddd,1H,
3
Ha(10), 2J¼14.2, J¼8.0 and 6.7 Hz), 2.72 (ddd, 1H, Hb(10), 2J¼14.2,
3J¼8.7 and 6.5 Hz), 2.75 (br d,1H, H(600), 3J¼9.5), 3.05 (br d,1H, H(200),
3J¼9.5), 3.62 (dd, 1H, H(2), 3J¼8.0 and 6.5 Hz), 3.69 and 3.74 (both s,
2ꢂ3H, 2OCH3), 4.24 (dd,1H, H(20), 3J¼8.7 and 6.7 Hz), 6.40 (br s,1H, H
6.66. Found: C, 56.87; H, 5.68; N, 6.60. R
*
,S
-4g: Colorless thick oil; 1H
*
NMR
d
2.49 (ddd,1H, Ha(10), 2J¼14.3, 3J¼8.2 and 6.6 Hz), 2.71 (ddd,1H,
3
Hb(10), 2J¼14.3, J¼9.2 and 6.3 Hz), 3.11 (dd, 1H, Ha(400), 2J¼17.4,
3J¼11.3 Hz), 3.18 (dd,1H, Hb(400), 2J¼17.4, 3J¼12.5 Hz), 3.50, 3.71, 3.73,
and 3.82 (all s, 4ꢂ3H, 4OCH3), 3.56 (dd, 1H, H(2), 3J¼8.2 and 6.3 Hz),
4.08 (dd, 1H, H(500), 3J¼12.5 and 11.3 Hz), 4.64 (dd, 1H, H(20), 3J¼9.2
(500)), 7.25e7.36 (m, 5H, C6H5); 13C NMR 24.9 and 28.6 (C(800) and C
d
(900)), 32.7 (C(10)), 33.6(C(1000)), 40.3and43.2 (C(100)) and(C(700)), 49.2
(HC(2)), 52.55 and 52.6 (2OCH3), 57.7 (C(600)), 64.8 (HC(20)), 67.1 (C
(200)),127.6 (p-C),128.3 and 128.5 (2 o-C and 2 m-C),139.6 (i-C),143.2
(C(500)), 169.9 and 170.2 (2COO); MS (m/z, %): 370 (3, Mþ), 339 (2,
MþꢁOCH3), 225 (100),175 (4),171 (6),143 (4),115 (28), 91 (8), 77 (6).
and 6.6 Hz), 7.25e7.37 (m, 5H, C6H5); 13C NMR 32.5 (H2C(10)), 36.7
d
(H2C(400)), 48.9 (HC(2)), 52.1, 52.4, 52.6 and 52.65 (4OCH3), 64.5 (HC
(20)), 64.6 (C(500)),128.1 and 128.6 (2 o-C and 2 m-C),128.3 (p-C),137.7
and 138.3 (i-C and C(300)),162.3,169.5,169.6 and 171.1 (4COO); MS (m/
z, %): 420 (3, Mþ), 389 (4, MþꢁOCH3), 361 (15, MþꢁCO2CH3), 319 (9),
288 (9), 275 (26), 235 (34), 203 (10), 175 (33), 171 (35), 143 (24), 115
(100), 59 (22). Anal. Calcd for C20H24N2O8: C, 57.14; H, 5.75; N, 6.66.
Found: C, 56.84; H, 5.69; N, 6.41.
4.2.8. Dimethyl 2-[2-(5-metoxycarbonyl-3,4-diazatricyclo[5.2.1.02,6
]
dec-4-en-3-yl)-2-phenylethyl]malonate (4f). The residue from re-
action of 1a (281 mg, 1.2 mmol) and 3c (233 mg, 1.2 mmol) in the
presence of Sc(OTf)3 (30 mg, 0.06 mmol) was purified by column
chromatography (benzeneeEtOAc, 9:1) to give diastereomeric
R
*
,R
*
-4f (324 mg, 63%) and R
*
,S
*
-4f (164 mg, 32%). R
*
,R
*
-4f: Color-
4.2.10. Methyl 1-benzoyl-4,5-dihydro-5-methoxycarbonyl-5-methyl-
1H-pyrazol (3e). Benzoyl chloride (0.70 g, 5 mmol) was added to
a solution of pyrazoline 3a (0.50 g, 3.5 mmol) in anhydrous pyridine
less thick oil; 1H NMR
d
0.97e1.50 (m, 6H, H2C(800), H2C(900) and H2C
(1000)), 2.28 and 2.55 (both m, 2ꢂ1H, H(100) and H(700)), 2.49 (ddd,

9158
Y.V. Tomilov et al. / Tetrahedron 66 (2010) 9151e9158
(10 mL) and the mixture was stirred at 100 ꢀC for 5 h. Then a re-
action mixture together with a residue formed was transferred into
hydrochloric acid (50 mL, 10%) at 0e10 ꢀC and the aqueous layer
was extracted with dichloromethane (3ꢂ30 mL). The combined
organic layer was washed with 10% aq NaHCO3 and dried over
MgSO4. After removal of the solvent, the substituted pyrazoline 3e
(0.83 g, 96%) was obtained as pale yellow crystals; mp 96e97 ꢀC; IR
(CHCl3) 1746 br (C]O), 1644, 1605, 1578, 1449, 1412 cmꢁ1; 1H NMR
4.2.11.2. Method B. A mixture of cyclopropane 1a (281 mg,
1.2 mmol), pyrazoline 3e (99 mg, 0.4 mmol), and Sc(OTf)3 (20 mg,
0.04 mmol) in 3 mL dichloroethane was refluxed for 12 h. After
cooling and removal of the solvent, the residue was separated by
silica gel column chromatography (benzeneeEtOAc, 5:1) to give
unreacted pyrazoline 3e (74 mg, 75%) and a mixture of anti- and
syn-5e (42 mg, 22%), which 1H and 13C NMR spectra were the same
as for the samples prepared above.
d
1.78 (s, 3H, CH3), 2.85 and 3.23 (both dd, 2ꢂ1H, H2C(4), 2J¼18.2,
3J¼1.7 Hz), 3.78 (s, 3H, OCH3), 6.86 (t, 1H, H(3), 3J¼1.7 Hz), 7.40 (m,
1H, 2 m-CH), 7.46 (m, 1H, p-CH), 7.82 (m, 2H, o-CH); 13C NMR
d 21.8
Acknowledgements
(CH3), 47.5 (C(4), 52.9 (OCH3)), 65.1 (C(5)), 127.7 (2 o-C), 129.6 (2 m-
C), 131.0 (p-C), 134.2 (i-C), 144.3 (C(3)), 172.0 (COO); MS (m/z, %):
246 (7, Mþ), 215 (1, MþꢁOCH3), 187 (43, MþꢁCO2CH3), 105 (100), 77
(56), 59 (19). Anal. Calcd for C13H14N2O3: C, 63.40; H, 5.73; N, 11.38.
Found: C, 63.61; H, 5.79; N, 11.23.
This work was financially supported by the Russian Federation
President Council for Grants (Program for the State Support of
Leading Scientific Schools of RF, Grant NSh-8242.2010.3) and
Ministry of Education and Science (Government Contract
02.740.11.0258).
4.2.11. Trimethyl 1-benzoyl-3-methyl-8-phenyl-1,2-diazabicyclo[3.3.0]
octane-3,6,6-tricarboxylate (5e).
Supplementary data
4.2.11.1. Method A. Benzoyl chloride (84 mg, 0.6 mmol) was
added to a solution of pure anti-5a (120 mg, 0.32 mmol) in anhy-
drous pyridine (3 mL) and the mixture was stirred at 80 ꢀC for 2 h.
After cooling and removal of the solvent under reduced pressure,
the residue was dissolved in CH2Cl2 (5 mL) and washed with 10% aq
NaHCO3 (3 mL) at 30e35 ꢀC. Then aqueous solution was extracted
with CH2Cl2 (5 mL), the combined organic layer was washed with
1% aq HCl (5 mL), and dried over MgSO4. The solvent was removed
in vacuo to afford compound anti-5e (144 mg, 94%) as colorless
crystals; mp 162e164 ꢀC; IR (KBr) 1740 br (O]CeO), 1636 (O]
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.09.092.
References and notes
1. Reissig, H. U.; Zimmer, R. Chem. Rev. 2003, 103, 1151.
2. Beal, R. B.; Dombroski, M. A.; Snider, B. B. J. Org. Chem. 1986, 51, 4391.
3. Shimada, S.; Hashimoto, Y.; Sudo, A.; Hasegawa, M.; Saigo, K. J. Org. Chem. 1992,
57, 7126.
4. Yadav, V. K.; Sriramurthy, V. Org. Lett. 2004, 6, 4495.
5. Yadav, V. K.; Sriramurthy, V. Angew. Chem. 2004, 116, 2723.
6. Pohlhaus, P. D.; Johnson, J. S. J. Org. Chem. 2005, 70, 1057.
7. Min, S.; Yang, Y. H.; Bo, X. Tetrahedron 2005, 61, 1893.
8. Bernard, A. M.; Frongia, A.; Piras, P. P.; Secci, F.; Spiga, M. Org. Lett. 2005, 7, 4565.
9. Graziano, M. L.; Iesce, M. R. J. Chem. Res. 1987, 362.
10. Carson, C. A.; Kerr, M. A. J. Org. Chem. 2005, 70, 8242.
11. Wurz, R. P.; Charette, A. B. Org. Lett. 2005, 7, 2313.
12. Saigo, K.; Shimada, S.; Hasegawa, M. Chem. Lett. 1990, 905.
13. Graziano, M. L.; Iesce, M. R.; Cermola, F. J. Chem. Res. 1996, 82.
14. Korotkov, V. S.; Larionov, O. V.; Hofmeister, A.; Magull, J.; de Meijere, A. J. Org.
Chem. 2007, 72, 7504.
15. Yu, M.; Pagenkopf, B. L. Org. Lett. 2001, 3, 2563.
16. Yu, M.; Pagenkopf, B. L. J. Am. Chem. Soc. 2003, 125, 2563.
17. Liu, L.; Montgomery, J. J. Org. Lett. 2007, 9, 3885.
18. Perreault, C.; Goudreau, S. R.; Zimmer, L. E.; Charette, A. B. Org. Lett. 2008, 10,
689.
19. Cardona, F.; Goti, A. Angew. Chem. 2005, 117, 8042.
20. Sibi, M. P.; Ma, Z. H.; Jasperse, C. P. J. Am. Chem. Soc. 2005, 127, 5764.
21. Ganton, M. D.; Kerr, M. A. J. Org. Chem. 2004, 69, 8554.
22. Lebold, T. R.; Kerr, M. A. Org. Lett. 2009, 11, 4357.
23. England, D. B.; Kuss, T. D. O.; Keddy, R. G.; Kerr, M. A. J. Org. Chem. 2001, 66,
4704.
24. Blanchard, L. A.; Schneider, J. A. J. Org. Chem. 1985, 51, 1372.
25. Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1353.
26. Pohlhaus, P. D.; Sanders, S. D.; Parsons, A. T.; Li, W.; Johnson, J. S. J. Am. Chem.
Soc. 2008, 130, 8642.
CeN), 1576, 1540, 1496, 1436 cmꢁ1; 1H NMR
d 2.00 (s, 3H, CH3), 2.11
(dd, 1H, Hanti(7), 2J¼14.3, 3J¼10.4 Hz), 2.27 (dd, 1H, Hsyn(4), 2J¼13.2,
3J¼11.9 Hz), 2.52 (dd, 1H, Hanti(4), 2J¼13.2, 3J¼6.7 Hz), 3.16 (dd, 1H,
Hsyn(7), 2J¼14.3, 3J¼7.7 Hz), 3.72 (s, 3H, OCH3 at C(3)), 3.80 and 3.84
(both s, 2ꢂ3H, 2OCH3), 4.06 (dd, 1H, H(8), 3J¼10.4 and 7.7 Hz), 4.86
(dd,1H, H(5), 3J¼11.9 and 6.7 Hz), 6.71 (br dd, 2H, 2 o-CH, 3J¼7.9 and
1.3 Hz), 6.86 (dd, 2H, m-CH, 3J¼7.9 and 7.5 Hz), 7.01 (tt, 1H, p-CH,
3J¼7.5 and 1.3 Hz), 7.12 (br dd, 2H, 2 m-CH, 3J¼7.7 and 7.3 Hz), 7.19
(br dd, 2H, o-CH, 3J¼7.7 and 1.5 Hz), 7.24 (tt, 1H, p-CH, 3J¼7.3 and
1.5 Hz); 13C NMR
d 26.4 (CH3), 39.5 (C(7)), 43.0 (C(4)), 52.9 (OCH3 at
C(3)), 53.3 and 53.4 (2OCH3), 58.6 (C(6)), 66.5 (C(5)), 68.5 (C(3)),
69.9 (C(8)), 127.2 (2 m-C from Bz), 127.7 (p-C), 128.1 (2 m-C), 128.2
(2ꢂ2 o-C), 129.3 (p-C from Bz), 135.8 (i-C from Bz), 137.0 (i-C), 169.7
and 170.9 (2COO), 169.9 (C]O), 172.8 (COO at C(3)). HRMS calcd for
C26H28N2O7: MþH, 481.1969; MþNa, 503.1789. Found: m/z
481.1960, 503.1783.
Similarly, from pure syn-5a (119 mg, 0.32 mmol) and benzoyl
chloride (82 mg, 0.6 mmol) compound syn-5e (141 mg, 92%) was
obtained as colorless thick oil; 1H NMR
d 1.74 (s, 3H, CH3), 2.17 (dd,
1H, Ha(7), 2J¼14.1, 3J¼10.6 Hz), 2.19 (dd, 1H, Ha(4), 2J¼12.2,
3J¼5.9 Hz), 2.50 (dd, 1H, Hb(4), 2J¼12.2, 3J¼11.8 Hz), 3.14 (dd, 1H,
Hb(7), 2J¼14.1, 3J¼7.8 Hz), 3.80, 3.85 and 3.90 (all s, 3ꢂ3H, 3OCH3),
4.56 (dd, 1H, H(8), 3J¼10.6 and 7.8 Hz), 4.74 (dd, 1H, H(5), 3J¼11.8
and 5.9 Hz), 6.82 (br dd, 2H, 2 m-CH, 3J¼7.7 and 6.9 Hz), 6.85 (dd,
2H, o-CH, 3J¼7.7 and 1.8 Hz), 6.94 (tt, 1H, p-CH, 3J¼6.9 and 1.8 Hz),
7.02 (br dd, 2H, 2 m-CH, 3J¼7.9 and 7.3 Hz), 7.15 (br t, 1H, p-CH,
27. Sapeta, K.; Kerr, M. A. Org. Lett. 2009, 11, 2081.
28. Jeffery, G. H.; Vogel, A. I. J. Chem. Soc. 1948, 1804.
29. White, D. A. Synth. Commun. 1977, 7, 559.
30. Touillaux, R.; Tinant, B.; Meerssche, M. V.; Dereppe, J. M. J. Chim. Phys. Phys.
Chim. Biol. 1980, 77, 319.
€
31. Auwers, K.; Konig, F. Liebigs Ann. Chem. 1932, 496, 27.
32. Hamada, M.; Okamoto, A. Botyu-Kagaku 1953, 18, 70; Chem. Abstr. 1954, 48,
9332.
33. Becker, K. B.; Hohermuth, M. K. Helv. Chim. Acta 1979, 207, 2025.
34. Ouyahia, A. A.; Leroy, G.; Weiler, J.; Touillaux, R. Bull. Soc. Chim. Belg. 1976, 85,
545.
35. Schweizer, E. E.; Kim, C. S. J. Org. Chem. 1971, 36, 4033.
36. Gorpinchenko, V. A.; Yatsynich, E. A.; Petrov, D. V.; Karachurina, L. T.;
Hisamutdinova, R. U.; Baschenko, N. Z.; Dokichev, V. A.; Tomilov, Y. V.; Yunusov,
M. S.; Nefedov, O. M. Pharm. Chem. J. (Russ.) 2005, 39, 9.
37. Buchner, E.; Papendieck, A. Liebigs Ann. Chem. 1893, 273, 232.
38. Doyle, M. P.; Colsman, M. R.; Dorow, R. L. J. Heterocycl. Chem. 1983, 20, 943.
3J¼7.3 Hz), 7.17 (br d, 2H, o-CH, 3J¼7.9 Hz); 13C NMR
d 21.1 (CH3),
39.0 and 41.5 (C(4) and C(7)), 53.1, 53.3 and 53.4 (3OCH3), 58.3 (C
(6)), 66.8 and 68.4 (C(5) and C(8)), 68.5 (C(3)), 127.1,127.9,128.6 and
128.7 (2ꢂ2 o-C and 2ꢂ2 m-C), 127.5 and 129.5 (2 p-C), 135.4 and
136.9 (2 i-C), 166.7, 169.3, 170.9 and 173.4 (3COO and C]O). Anal.
Calcd for C26H28N2O7: C, 64.99; H, 5.87; N, 5.83. Found: C, 64.78; H,
5.94; N, 5.62.