Synthesis of β-functionalized α,β-unsaturated oximes via silylation of nitro compounds

Article abstract of DOI:10.1055/s-2002-23539

A general method for the synthesis of conjugated enoximes 2 via silylation of functionalized aliphatic nitro compounds 1 has been elaborated. The configuration of obtained products has been determined by NMR spectroscopy.

Full text of DOI:10.1055/s-2002-23539

PAPER
635
Synthesis of -Functionalized , -Unsaturated Oximes via Silylation of Nitro
Compounds1
Synthesis of
,
-U
i
nsatur
a
t
tedO
x
a
imes from
N
itroC
y
ompounds M. Danilenko,a Alexander A. Tishkov,*b Sema L. Ioffe,*b Ilya M. Lyapkalo,a Yury A. Strelenko,b
Vladimir A. Tartakovskyb
a
Moscow Chemical Lyceum, 4 Tamozheny proezd,109033, Moscow, Russian Federation
Fax +7(095)3623440; E-mail: dan@1303.ru
b
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 117913, Moscow, Russian Federation
Fax +7(095)1355328; E-mail: tishkov@cacr.ioc.ac.ru
Received 10 January 2002
X(R1)C=C(R2)–C(R3)=NOH (2), where R1, R2, R3 = H,
Abstract: A general method for the synthesis of conjugated
alkyl, aryl, CO2Me, and X = electron-withdrawing group.
enoximes 2 via silylation of functionalized aliphatic nitro com-
pounds 1 has been elaborated. The configuration of obtained prod-
ucts has been determined by NMR spectroscopy.
The interest towards conjugated enoximes is conditioned
by their versatility as building blocks for synthesis (e.g.
Key words: nitro compounds, elimination, stereoselectivity, silyla- for the preparation of
, -unsaturated carbonyl
compounds8 and nitriles,9 aziridines,10 pyridines,11 isox-
azoles,12 and pyrazole-N-oxides.13 Moreover, some
enoximes were shown to possess a wide spectrum of bio-
logical activities.14 , -Unsaturated oximino-fragments
are incorporated in the range of natural macrolides, which
have shown a high antitumor activity.15 The enoximes
having an electron-withdrawing heterocyclic substituent
in the -position (X = pyridinium, pirimidinium and imid-
azolium) are efficient reactivators of the phosphorylated
cholinesterase.16 However, despite the shown interest in
this class of compounds, the general method for synthesis
of conjugated enoximes has not been elaborated so far.17
tion, conjugated enoximes
During the recent decade we have been studying the silyl-
ation as a novel strategy for the use of aliphatic nitro com-
pounds (ANC) in organic synthesis. In the framework of
this approach, the silylation of readily available function-
alized ANC is of considerable interest, since they have
been transformed into synthetically useful N,N-bis(si-
loxy)amino-cyclopropanes,2,3 -dihydrofurans2 and -alk-
enes,4 N,N-divinylhydroxylamines,5 as well as into other
products.6 Most of above mentioned reactions are
chemo-, regio- and stereoselective, and are therefore syn-
thetically promising methods.
The main results of silylation of ANC 1 into derivatives 6
are presented in Scheme 1 and Table 1. The desilylation
of products 6 affords the target enoximes 2 in good yields.
This paper deals with one of the most general process tak-
ing place upon silylation of readily available ANC7 of
general formula XCH(R1)–CH(R2)–CH(R3)NO2 (1), i.e.
the formation of silylated , -unsaturated oximes, which
can be easily desilylated to give enoximes
The reaction mechanism depends on the nature of both
substituents (first and foremost R2) and silylating reagent
to be used. Thus, if R2 is an electron-withdrawing CO2Me
R2
i
X
N
O
i
pathway 1
R1 R3
Me3SiOH
R2
4
R2
R2 OSiMe3
X
N
OSiMe3
i
R1 R3
X
NO2
X
N
O
6
i
R1 R3
R1 R3
R2 OSiMe3
N
Me3SiOH
ii
3
X
i
1
pathway 2
OSiMe3
R1 R3
R2
5
X
N
OH
R1 R3
2
Scheme 1 Reagents and conditions: i: Silylation, conditions are indicated in Table 1; ii: NH4F/MeOH
Synthesis 2002, No. 5, 08 04 2002. Article Identifier:
1437-210X,E;2002,0,05,0635,0647,ftx,en;P00102SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

636
V. M. Danilenko et al.
PAPER
Table 1 Silylation of Nitro Compounds 1
Entry 1 R1
R2
R3
X
Silylating agent
Reaction Cond. Prod- E/Z
Yield En-
E/Z
Yield
(%)b,c
T, oC Time, h uct
(%)a oxime 2
1
2
1a
1b
1c
1d
H
H
H
H
H
H
CO2Me Me3SiBr/Et3N
20
20
20
0
40
48
1
6a
6b
6c
6dg
6e
6f
5:1 71
2a
2b
2c
2d
2e
2f
–
5:1 65 (68)d
21:13 39
H
H
CN
Me3SiBr/Et3N
Me3SiCl/Et3N
10:9 67e
1:0 67
1:0 61
1:0 65
3
H
H
NO2
1:0 45 (44)f
1:0 56 (18)h
1:0 59 (60)h
1:0 38 (60)j
4
H
H
CO2Me Me3SiOTf/Et3N
3
5
1e Me
H
H
CO2Et
CO2Et
Me3SiOTf/Et3N
Me3SiOTf/Et3N
0
20
20
20
48
96
400
i
i
6
1f
1g
1h
1i
H
H
H
H
H
Me
H
H
20
20
–
–
7
Me
H
CO2Me Me3SiBr/Et3N
7k
–
90
–
–
–
8
Ph
H
CO2Me Me3SiOTf/Et3N –22
6h
6i
5:4 95e
1:0 65
2h
2i
5:4 26
1:1 70
1:0 58
9
Ph
CO2Me Me3SiBr/Et3N
20
10
1j
H
CH2CH2 CO2Me Me3SiBr/Et3N
CO2Me
–28
6j
2j
11
12
13
14
15
16
17
18
19
20
21
22
23
24
1k CO2Me
1l
1m H
H
H
H
CO2Me Me3SiBr/Et3N
CO2Me Me3SiCl/Et3N
–28
20
72
1
6k
6l
–
90
2k
2l
56
H
CO2Me
H
3:7 81
3:7 79 (73)f
1:0 86
i
i
CO2Me CO2Me Me3SiOTf/Et3N
20
16
96
5
6m
6n
6o
6p
6q
6r
6s
–
–
–
–
2m
2n
2o
2p
2q
2r
2s
2t
2u
–
i
i
1n
1o
1p
H
H
H
H
CO2Me CN
COPh
Me3SiOTf/Et3N
Me3SiBr/Et3N
5
1:0 47
CO2Me
H
20
1:1 86
1:6 90
2:1 80
1:4 90
0:1 73
1:4 90
1:1 80
61
0:1 59 (57)f
0:1 81 (80)f
2:1 60
CO2Me Me
CO2Me
CO2Me Ph
CO2Me Me3SiCl/Et3N
CO2Me Me3SiCl/Et3Nl
CO2Me BSA
20
1
1q Me
H
20
1
1r
1s
1t
H
H
H
H
20
1
0:1 85 (87)m
0:1 66 (62)m
1:4 64 (60)f
0:1 72 (75)f
–
CO2Me CO2Me CO2Me BSA
20
1
CO2Me
H
CN
CN
Me3SiCl/Et3N
Me3SiCl/Et3N
20
1
6t
1u
CO2Me Me
20
1
6u
8k
1v CO2Me Ph
H
H
H
CO2Me Me3SiBr/Et3N
–28
–28
–28
60
60
24
–
–
–
–
–
–
1w H
1x
Ph
Ph
COPh
Me3SiBr/Et3N
Me3SiBr/Et3N
9k
83
–
–
H
COMe
10k
53
1l
41
a Yield refers to distilled products.
b Yield refers to ANC 1.
c Yield refers to recrystallized products.
d Yield for silylation of 1a with Me3SiOTf/Et3N (20 h, –28 °C).
e The yield was determined by 1H NMR spectrum with internal standard (ClCH2CH2Cl).
f Yield for silylation with BSA.
g CH2=C(OSiMe3) group instead of MeCO fragment.
h Yield for silylation with Me3SiBr/Et3N. 1d: 72 h, –28 °C, 1e: 150 h, 20 °C.
i The crude enoxime 6 was subjected to desilylation without NMR analysis.
j Yield for silylation of independently synthesized 3f by means of Me3SiOTf/Et3N (3 h, –30 °C).
k See Figure 1.
l The use of BSA for silylation of 1q leads to the formation of N,N-divinylhydroxylamine (see ref.5).
m Yield for silylation with Me3SiCl/Et3N.
group, the use of rather weak silylating reagents reactive nitroso alkenes 4.19 The subsequent 1,5-migration
{Me3SiCl/Et3N or BSA [N,O-bis(trimethylsilyl)acet- of proton followed by silylation of oximino group furnish-
amide]} triggers a 1,3-N,C-elimination of ‘Me3SiOH’ es derivatives 6 (pathway 1, Scheme 1).
from the initially formed silyl nitronates 3 to give highly
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of , -Unsaturated Oximes from Nitro Compounds
637
Ph
OR
COOMe
N
MeOOC
MeOOC
OSiMe3
Ph
OSiMe3
N
N
Ph
N
O
Me3SiO
7, see ref.4
OSiMe3
Ph
OSiMe3
10, R = SiMe3
11, R = H
OSiMe3
8, see ref.2
9, see ref.2
see ref.18
Figure 1
Table 2 The Values of 3J(1H,13C) (Hz) for Some Enoximesa
At the same time, the absence of electron-withdrawing
group in -position (R2 CO2Me) prevents the 1,3-N,C-
elimination of ‘Me3SiOH’, and the silylation of ANC 1
with either Me3SiCl/Et3N or BSA leads to stable silyl ni-
tronates 3 under the reaction conditions.20 However, the
use of stronger reagents (Me3SiX/Et3N, X = Br or OTf)
for silylation of 1 causes the so-called ‘double’ silylation
Eno-
xime
A
C1
C2
3J(1H,
3J(1H,
13C1)
13C2)
Z-6l CO2Me
E-6l CO2Me
CO2Me
C(H)NOSiMe3 10.5
8.2
C(H)=NO CO2Me
SiMe3
7.0
10.0
to give N,N-bis(silyloxy)enamines
5 (pathway 2,
Scheme 1),4,21 which undergo 1,4-N,C-elimination of
‘Me3SiOH’ to form the products 6 upon the influence of
excess of silylating reagent if X is an electron-withdraw-
ing group.
Z-2l CO2Me
E-2l CO2Me
CO2Me
C(H)=NOH
10.6
7.2
8.3
C(H)=NO CO2Me
H
10.2
Z-6p CO2Me
E-6p CO2Me
CO2Me
C(Me)NOSiMe3 11.2
6.6
8.7
Besides the formation of enoximes 6, the silylation of
some ANC 1 can give rise to other products, namely N,N-
bis(silyloxy)enamine 7 (Entry 7, Table 1), cyclopropane 8
(Entry 22, Table 1), dihydrofuran 9 (Entry 23, Table 1)
and non-functionalized enoxime 10 (Entry 24, Table 1)
(see Figure 1). The chemoselectivity in these cases is gov-
erned by nature of substitution in 3 (R2 and R1). The prob-
able mechanisms of formation of 7–10 are considered in
our recent publications.2,4,18
C(Me)=NO CO2Me
SiMe3
–
Z-2p CO2Me
Z-6r CO2Me
E-6r CO2Me
CO2Me
CO2Me
C(Me)=NOH
11.6
6.4
7.1
–
C(Ph)NOSiMe3 10.8
C(Ph)=NO CO2Me
SiMe3
6.4
Z-2r CO2Me
Z-6s CO2Me
CO2Me
CO2Me
C(Ph)=NOH
11.7
10.5
7.0
6.7
The structure of products 6 and enoximes 2 was proved by
1H, 13C, 29Si and 15N NMR spectroscopy. Additional de-
tails are given for the determination of configuration
around C,C- and C,N-double bonds in Table 2 and
Figure 2 .
C(CO2Me)=
NOSiMe3
Z-2s CO2Me
CO2Me
CO2Me
C(CO2Me)=
NOH
11.7
7.0
The easiest method for assignment of disubstituted C,C-
double bond configuration is a comparison of vicinal
1H,1H-coupling constants, which should be bigger for
trans-isomers (I, Figure 2).22
Z-2t CN
E-2t CN
C(H)=NOH
–
6.5
9.5
C(H)=NO CO2Me
H
6.6
Z-6u CN
E-6u CN
CO2Me
C(Me)=NO
SiMe3
11.6
6.6
6.3
8.4
6.5
The substituents arrangement in trisubstituted C,C-double
3
bond has strong effects on the J(1H,13C) coupling con-
stants [3J(1H,13C1) > 3J(1H,13C2)] [II, Figure 2, Table 2].23
C(Me)=NO CO2Me
SiMe3
The shielding of proton in CH=N group of anti-isomers of
aldoximes 2 and 6 allows us to assign the geometry of
C,N-double bond using 1H NMR spectra.24 However, the
data for both syn- and anti-isomers are needed to use this
rule. If one isomer is not available, a different rule about
Z-2u CN
CO2Me
C(Me)=NOH
11.5
a See Figure 2, II.
R = H, SiMe3
C1
OR
N
OR
H
H
C1
C1
N
D
N
A
H
A
D
N
OR
C2
OR
B
B
H
C2
C2
anti-
H
A
H
H
syn
anti
2J1 15
>
2J1 15
syn-
cis-
3J1 13
>
3J1 13
trans-
H,
N
H,
N
H, C1
H, C2
δ(13C)C1anti > δ(13C)C1
syn
δ(1H)syn > δ(1H)anti
trans
cis
3J1
1
>
3J1
1
H, H
H, H
I
II
III
IV
Figure 2
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

638
V. M. Danilenko et al.
PAPER
2J(1H,15N) coupling constants gives the structural infor-
cooled down to –65 °C. A solution of acrylonitrile (0.66 mL, 10
mmol) in CH2Cl2 (1 mL) was added simultaneously, the tempera-
ture was allowed to reach 0 °C in 20 min. A solution of
NaHSO4 H2O (1.5 g, 11 mmol) in H2O (10 mL) was added and the
mixture was extracted with CHCl3 (3 15 mL). The combined or-
ganic layers were washed with H2O and brine, dried (MgSO4) and
evaporated. The residue was subjected to column chromatography
(silica gel, CHCl3) to give 1b (0.23 g, 20%) as a colorless oil and 4-
nitroheptanedinitrile (0.26 g, 16%) as white crystals; mp 63–65 °C
(CH2Cl2).
2
mation (III, Figure 2). The absolute values of J(1H,15N)
lie in the range of 7–15 Hz for syn- and 0–5 Hz for anti-
isomers.25
The assignment of configuration around C,N-double bond
in ketoximes can be made by 13C NMR spectra (IV,
Figure 2). The carbon atom in syn-arrangement towards
OX-group is shifted to upper fields in comparison to sig-
nal from the same carbon in the opposite isomer.26
1H NMR (CDCl3): = 2.35 (m, 2 H, CH2), 2.56 (t, 2 H, NCCH2,
3J = 7.2 Hz), 4.53 (t, 2 H, O2NCH2).
Thus, we have elaborated a method for synthesis of
-
functionalized conjugated enoximes from readily avail-
able -functionalized nitro compounds. Since Michael ad-
dition of nitroalkanes to electron-deficient alkenes is a
good developed synthetic transformation,27 the method
presented herein can be considered as a convenient proto-
col for oximinoalkylation of Michael substrates
(Scheme 2).
13C NMR (CDCl3): = 15.0 (CH2CN), 23.2 (CH2), 73.2 (CH2NO2),
118 (CN).
14N NMR (CDCl3): = –0.2 (NO2,
100 Hz), –131.7 (CN,
1/2
480 Hz).
1/2
Anal. Calcd for C4H6N2O2: C 42.11; H 5.30. Found: C 42.36; H
5.00.
Methyl 4-Nitro-3-phenylbutanoate (1h)
To a solution of ethyl cinnamate (3.52 g, 20 mmol) in MeNO2 (11
mL, 200 mmol) at 0 °C was added DBU (3.0 mL, 20 mmol). The
reaction mixture was stirred at r.t. for 4 h. A solution of
NaHSO4 H2O (3.5 g, 25 mmol) in H2O (50 mL) was added and the
mixture was extracted with CHCl3 (3 15 mL). The combined or-
ganic layers were washed with H2O and brine, dried (MgSO4) and
evaporated. The residue was dissolved in MeOH (100 mL), conc.
H2SO4 (0.01 mL) was added and refluxed for 100 h. The solvents
were evaporated, the residue was dissolved in CH2Cl2 (20 mL),
washed with H2O, brine, dried (MgSO4) and evaporated. The resi-
due was distilled to give 1h (3.02 g, 67%, bp 110–114 °C/0.6 Torr)
as a colorless oil.
R3
, Michael addition
NO2
2. Silylation
3. Desilylation
1.
R2
R2
X
X
NOH
R1
R1 R3
X = electron withdrawing group
Scheme 2
Judging by some previously observed results,28 non-func-
tionalized N,N-bis(silyloxy)enamines 5 (R1, R2, R3, X = H
or alkyl) can undergo an 1,4-N,C-elimination of
‘Me3SiOH’ to give the corresponding products 6 upon the
influence of strong silylating reagent (Me3SiOTf/Et3N,
r.t.) (Scheme 1). This fact creates the prerequisites for de-
velopment of general procedures for the preparation of
conjugated enoximes by silylation of aliphatic nitro com-
pounds. This problem will be the subject of our further in-
vestigations.
2
1H NMR (acetone-d6): = 2.80 (dd, 1 H, CH2CO2Me, J = 16.2,
2
3
3J = 8.1 Hz), 2.89 (dd, 1 H, CH2CO2Me, J = 16.2, J = 6.6 Hz),
3.57 (s, 3 H, OMe), 3.99 (m, 1 H, CH), 4.86 (dd, 1 H, NO2CH2,
3
2J = 13.2, J = 5.9 Hz), 4.97 (dd, 1 H, NO2CH2, 2J = 13.2, 3J = 8.8
Hz), 7.23–7.41 (m, 5 H, C6H5).
13C NMR (acetone-d6): = 38.1 and 41.3 (CH2C=O and CH), 51.9
(OCH3), 80.0 (CH2NO2), 128.4, 128.5 and 129.6 (CHPh), 140.2
(CPh), 171.7 (C=O).
14N NMR (acetone-d6): = 2.5 (NO2,
170 Hz).
NMR spectra were recorded on a Bruker AM-300 instrument.
Chemical shifts were measured relative to solvent residual peak,29
internal reference (SiMe4, 0 ppm, for 29Si) and external reference
(MeNO2, 0 ppm, for 14N and 15N). The INEPT pulse sequence was
used for 29Si and 15N signals observation, GATED, SPT and SPT
CV pulse sequences were used to observe 3J(1H,13C) coupling con-
stants.
1/2
Anal. Calcd for C11H13NO4: C 59.19; H 5.87. Found: C 59.10; H
5.95.
Dimethyl 2-(Nitromethyl)succinate (1l)
A mixture of nitromethane (0.81 mL, 15 mmol), dimethyl maleate
(1.88 mL, 15 mmol) and freshly dried and ground KF (0.44 g, 7.59
mmol) was stirred for 7 h at 90 °C, cooled down to r.t., diluted with
Et2O (20 mL) and poured into H2O (30 mL). The organic layer was
separated, the aqueous phase was back-extracted with Et2O (3 15
mL), the combined organic layers were washed with brine, dried
(MgSO4) and evaporated in vacuum. The residue was distilled in
vacuum to give 1l (770 mg, 25%, bp 110 °C/0.2 Torr) as a colorless
oil.
All reactions were performed under dry argon using CH2Cl2 and
CCl4 freshly distilled from CaH2. Petroleum ether refers to the frac-
tion having bp 60–70 °C.
Some starting nitro compounds 1 were prepared by literature proce-
dures: 1a,e,g,j30 1c,31 1d,32 1f,33 1i,34 1k,35 1m,36 1o,37 1q.5 Nitro
compounds 1b,h,l,n,p,r,s were prepared by Michael addition of ni-
tromethane, nitroethane, 1-(nitromethyl)benzene and methyl ni-
troacetate to acrylonitrile, ethyl cynamate and dimethyl maleate.
Compound 1t was synthesized by alkylation of dilithium salt of me-
thyl 3-nitropropionate with iodoacetonitrile and 1u was synthesized
by alkylation of methyl acetoacetate with iodoacetonitrile, followed
by transformation of resulting ketone into oxime and its oxidation.
1H NMR (acetone-d6): = 2.50 (dd, 1 H, CH2CO2Me, J = 18.5,
2
3J = 6.5 Hz), 2.60 (dd, 1 H, CH2CO2Me, J = 18.5, J = 6.5 Hz),
2
3
3.34 (m, 1 H, CHCO2Me), 3.48 (s, 3 H) and 3.54 (s, 3 H) (2 OMe),
2
3
4.49 (dd, 1 H, NO2CH2, J = 14.5, J = 5.2 Hz), 4.51 (dd, 1 H,
NO2CH2, 2J = 14.5, 3J = 7.1 Hz).
Anal. Calcd for C7H11NO6: C 40.98; H 5.40. Found: C 40.79; H
5.35.
4-Nitrobutanenitrile (1b)
To a solution of MeNO2 (5.37 mL, 100 mmol) in CH2Cl2 (10 mL)
at –25 °C was added DBU (1.50 mL, 10 mmol) and the mixture was
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of , -Unsaturated Oximes from Nitro Compounds
639
Methyl 4-Cyano-2-nitrobutanoate (1n)
15 mmol) was stirred for 8 h at 65 °C, cooled down to r.t., diluted
with Et2O (20 mL) and poured into H2O (30 mL). The organic layer
was separated, the aqueous phase was back-extracted with Et2O (3
15 mL), the combined organic layers were washed with brine,
dried (MgSO4) and evaporated in vacuum. The residue was stirred
with an aq solution of Na2CO3 (10%, 50 mL) during 1 h and extract-
ed with Et2O (3 15 mL) [in order to remove trimethyl (E)-prop-1-
ene-1,2,3-tricarboxylate]. The aqueous phase was acidified with
10% HCl to pH 2 and extracted with Et2O (5 15 mL). The com-
bined organic layers were washed with brine, dried (MgSO4) and
evaporated. The residue was distilled in vacuum to give 1s (1.38 g,
35%, 1:1 mixture of isomers, bp 130 °C/0.1 Torr) as a colorless oil.
To a solution of methyl nitroacetate (2.14 g, 18 mmol) in CH2Cl2 (7
mL) at 0 °C was added Et3N (2.5 mL, 18 mmol) and acrylonitrile
(1.2 mL, 18 mmol). The reaction mixture was stirred at r.t. for 47 h,
quenched with AcOH (1.4 mL, 25 mmol), poured into H2O (30 mL)
and extracted with CHCl3 (5 15 mL). The combined organic lay-
ers were washed with H2O and brine, dried (MgSO4) and evaporat-
ed. The residue was subjected to fractional vacuum distillation to
give 1n (1.62 g, 52%, bp 132–135 °C/0.5 Torr) as a yellowish oil.
1H NMR (CDCl3): = 2.58 (m, 4 H, 2 CH2), 3.87 (s, 3 H, OMe),
5.28 (br s, 1 H, O2NCH).
Anal. Calcd for C6H8N2O4: C 41.86; H 4.68. Found: C 41.58; H
4.92.
Isomer 1
2
1H NMR (acetone-d6): = 2.83 (dd, 1 H, MeO2CCH2, J = 17.4,
2
3
Dimethyl 2-(1-Nitroethyl)succinate (1p)
3J = 7.0 Hz), 2.95 (dd, 1 H, MeO2CCH2, J = 17.0, J = 7.4 Hz),
A mixture of nitroethane (1.08 mL, 15 mmol), dimethyl maleate
(1.88 mL, 15 mmol) and freshly dried and ground KF (0.44 g, 7.59
mmol) was stirred for 7 h at 100 °C, cooled down to r.t., diluted with
Et2O (20 mL) and poured into H2O (30 mL). The organic layer was
separated, the aqueous phase was back-extracted with Et2O (3 15
mL), the combined organic layers were washed with brine, dried
(MgSO4), and evaporated in vacuum. The residue was distilled in
vacuum to give 1p (1.15 g, 35%, 1:1 mixture of isomers, bp 90 °C/
0.2 Torr) as a colorless oil.
3.68, 3.72 and 3.86 (3 s, 3
3 H, 3 OMe), 3.90 (m, 1 H,
MeO2CCH), 5.86 (d, 1 H, NO2CH, 3J = 6.0 Hz).
Isomer 2
1H NMR (acetone-d6): = 2.79 (dd, 1 H, MeO2CCH2, J = 17.4,
2
3J = 5.8 Hz), 2.89 (dd, 1 H, MeO2CCH2, J = 17.4, J = 7.4 Hz),
2
3
3.68, 3.72 and 3.86 (3 s, 3
H, 3 OMe), 3.90 (m, 1 H,
MeO2CCH), 5.89 (d, 1 H, NO2CH, 3J = 5.7 Hz).
Anal. Calcd for C9H13NO8: C 41.07; H 4.98. Found: C 41.32; H
5.15.
Isomer 1
1H NMR (CDCl3): = 1.33 (d, 3 H, Me, 3J = 6.2 Hz), 2.99 (dd, 1 H,
CH2CO2Me, J = 17.0, J = 4.5 Hz), 3.22 (m, 1 H, MeO2CCH),
Methyl 3-Cyano-2-(nitromethyl)propanoate (1t)
2
3
BuLi (1.54 M hexane solution, 16.4 mL, 25.3 mmol) was added at
–35 °C to a solution of i-Pr2NH (3.60 mL, 25.7 mmol) in THF (50
mL) and HMPA (10 mL). The mixture was stirred at –35 °C for 10
min and cooled down to –78 °C. Then methyl 3-nitropropionate
(1.50 g, 11.3 mmol) was added. After stirring for 40 min, iodoace-
tonitrile (1.73 g, 11.3 mmol) was added and the temperature was al-
lowed to reach –25 °C in 4 h. Then AcOH (4.0 mL, 11.3 mmol) and,
after 5 min, H2O (50 mL) were added. The reaction mixture was al-
lowed to reach r.t. and extracted with Et2O (3 15 mL). The com-
bined organic layers were washed with H2O, sat. aq NaHCO3, H2O,
brine, dried (MgSO4) and evaporated. The residue was subjected to
column chromatography (silica gel, CHCl3) to give 1t (1.17 g, 60%)
as a colorless oil.
3.44 (s, 3 H) and 3.49 (s, 3 H) (2
OMe), 3.56 (dd, 1 H,
CH2CO2Me, 2J = 17.0, 3J = 10.0 Hz), 4.71 (m, 1 H, NO2CH).
Isomer 2
1H NMR (CDCl3): = 1.33 (d, 3 H, Me, 3J = 6.2 Hz), 2.40 (dd, 1 H,
CH2CO2Me, 2J = 17.0, 3J = 5.0 Hz), 3.30 (m, 1 H, CHCO2Me), 3.44
(s, 3 H) and 3.48 (s, 3 H) (2 OCH3), 3.57 (dd, 1 H, MeO2CCH2,
2J = 17.0, 3J = 7.7 Hz), 4.71 (m, 1 H, NO2CH).
Anal. Calcd for C8H13NO6: C 43.84; H 5.98. Found: C 44.10; H
5.89.
Dimethyl 2-[Nitro(phenyl)methyl]succinate (1r)
A mixture of 1-(nitromethyl)benzene (2.06 g, 15 mmol), dimethyl
maleate (3.76 mL, 30 mmol) and freshly dried and ground KF (0.44
g, 7.59 mmol) was stirred for 1.5 h at 90 °C, cooled down to r.t., di-
luted with Et2O (20 mL) and poured into H2O (30 mL). The organic
layer was separated, the aqueous phase was back-extracted with
Et2O (3 15 mL), the combined organic layers were washed with
brine, dried (MgSO4) and evaporated in vacuum. The residue was
distilled in vacuum to give 1r (2.53 g, 60%, 4:1 mixture of isomers,
bp 140 °C/0.3 Torr) as a colorless oil.
1H NMR (acetone-d6): = 2.98 (dd, 1 H, CH2CN, 2J = 17.3, 3J = 6.7
2
3
Hz), 3.05 (dd, 1 H, CH2CN, J = 17.3, J = 6.7 Hz), 3.70 (m, 1 H,
CHCO2Me), 3.78 (s, 3 H, OMe), 4.96 (m, 2 H, NO2CH2).
13C NMR (acetone-d6): = 17.7 (CH2CN), 39.9 (CH2C=O), 53.3
(OMe), 74.7 (CH2NO2), 117.9 (CN), 170.7 (C=O).
14N NMR (acetone-d6): = –1.4 (NO2,
60 Hz), –131.3 (CN,
1/2
670 Hz).
1/2
Anal. Calcd for C6H8N2O4: C 41.86; H 4.68. Found: C 42.02; H
4.65.
Major Isomer
1H NMR (CDCl3):
= 2.18 (dd, 1 H, MeO2CCH2, 2J = 17.0,
3J = 6.2 Hz), 2.53 (dd, 1 H, MeO2CCH2, J = 17.0, J = 4.7 Hz),
Methyl 2-(Cyanomethyl)-3-nitrobutanoate (1u)
2
3
3.42 and 3.61 (2 s, 2
H, 2 OMe), 3.93 (m, 1 H, MeO2CCH),
To a suspension of the sodium salt of methyl acetoacetate (prepared
from methyl acetoacetate (21.23 g, 0.18 mol) and Na (1.40 g, 0.061
mol) in benzene (40 mL)) was added dropwise iodoacetonitrile
(10.25 g, 0.061 mol) and the mixture was stirred for 10 h. The pre-
cipitated NaI was filtered off, the organic layer was washed with
H2O, brine, dried (MgSO4) and evaporated in vacuum. The residue
was distilled in vacuum to give methyl 2-(cyanomethyl)-3-oxobu-
tanoate (6.68 g, 71%, bp 96–100 °C/0.02 Torr) as a colorless oil. A
solution of methyl 2-(cyanomethyl)-3-oxobutanoate (2.4 g, 0.0155
mol), NH2OH HCl (1.10 g, 0.0158 mol) and NaOAc 3H2O (2.74 g,
0.023 mol) in aq MeOH (60%, 30 mL) was stirred for 3 h at r.t. and
evaporated in vacuum. The residue was extracted with CH2Cl2 (5
15 mL). The extracts were combined, washed 3 times with 10% aq
NaHCO3 solution, H2O, brine, dried (MgSO4) and evaporated to
5.88 (d, 1 H, NO2CH, 3J = 11.5 Hz), 7.30 (m, 5 H, C6H5).
Minor Isomer
1H NMR (CDCl3): = 2.53 (dd, 1 H, MeO2CCH2, 2J = 16.0, 3J = 4.0
Hz), 3.33 (s, 3 H) and 3.51 (s, 3 H) (2 OMe), 3.84 (m, 1 H,
2
3
MeO2CCH), 3.88 (dd, 1 H, MeO2CCH2, J = 16.0, J = 9.0 Hz),
5.74 (d, 1 H, NO2CH, 3J = 9.0 Hz), 7.30 (m, 5 H, C6H5).
Anal. Calcd for C13H15NO6: C 55.51; H 5.38. Found: C 55.78; H
5.26.
Trimethyl 1-Nitro-1,2,3-propanetricarboxylate (1s)
A mixture of methyl nitroacetate (1.79 g, 15 mmol), dimethyl male-
ate (3.76 mL, 30 mmol) and freshly dried and ground KF (0.88 g,
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

640
V. M. Danilenko et al.
PAPER
give methyl 2-(cyanomethyl)-3-(hydroxyimino)butanoate (1.24 g,
47%) as a white solid [mp 98–99 °C (pentane–Et2O)]. A solution of
trifluoroperacetic acid [generated from H2O2 (88%, 0.25 mL, 9.2
mmol) and trifluoroacetic anhydride (1.56 mL, 11 mmol) in MeCN
(2.3 mL) at 0 to 20 °C] was added in 30 min at r.t. to a vigorously
stirred suspension of NaHCO3 (2.1 g, 25 mmol) in a solution of urea
(0.1 g, 1.7 mmol) and methyl 2-(cyanomethyl)-3-(hydroxyimi-
no)butanoate (0.85 g, 5 mmol) in MeCN (9 mL). The reaction mix-
ture was stirred for 1 h, poured into H2O (40 mL) and extracted with
CH2Cl2 (5 25 mL). The combined organic layers were washed 5
times with 10% aq NaHCO3, dried (MgSO4) and evaporated. The
residue was treated with NH2OH HCl according to the above pre-
sented procedure (in order to remove the byproduct 2-(cyanometh-
yl)-3-oxobutanoate). The resulting mixture was subjected to
column chromatography to give 1u (0.37 g, 40%, 1:1 mixture of
isomers) as a colorless oil. The spectral and analytical data are given
for the mixture of isomers.
1H NMR (acetone-d6): = 1.66 (m, 3 H, Me), 2.90 (m, 2 H, CH2),
3.60 (m, 1 H, CHCO2Me), 3.78 (s, 3 H, OMe), 5.05 (m, 1 H,
NO2CH).
13C NMR [(CD3)2CO]: = 15.7 Me, 16.4 (CH2), 16.9 Me, 17.1
(CH2), 45.1 (CHC=O), 45.3 (CHC=O), 53.3 and 53.4 (2 OMe),
82.4 (CHNO2), 82.7 (CHNO2), 117.7 (CN), 118.2 (CN), 170.1,
170.5 (2 C=O).
(Z)-anti-6a
1H NMR (CDCl3): = 0.27 (s, 9 H, OSiMe3), 3.76 (s, 3 H, OMe),
6.01 (dd, 1 H, MeO2CCH, J = 12.0, J = 1.0 Hz), 6.69 (dd, 1 H,
CHCH=N, 3J = 12.0, 3J = 10.4 Hz) 8.95 (dd, 1 H, CH=N, 3J = 10.4,
3J = 1.0 Hz).
3
4
13C NMR (CDCl3):
= –1.1 (OSiMe3), 51.4 (OMe), 122.6
(MeO2CCH), 137.5 (CHCH=N), 152.4 (CH=N), 166.0 (C=O).
29Si NMR (CDCl3): = 27.61 (NOSiMe3).
Anal. Calcd for C8H15NO3Si: C 47.73; H 7.51; N 6.96; Si 13.95.
Found: C 47.69; H 7.46; N 6.91; Si 14.04.
Methyl 4-{[(Trimethylsilyl)oxy]imino}but-2-enenitrile (6b)
(Z)-anti-6b:(E)-anti-6b:(E)-syn-6b = 10:9:0.1.
(E)-anti-6b
1H NMR (CDCl3): = 0.22 (s, 9 H, OSiMe3), 5.62 (d, 1 H, NCCH,
3
3J = 16.4 Hz), 7.08 (dd, 1 H, CHCH=N, 3J = 16.4, J = 10.2 Hz),
7.85 (d, 1 H, CH=N, 3J = 10.2 Hz).
13C NMR (CDCl3): = 0.1 (OSiMe3), 104.4 (NCCH), 117.0 (CN),
144.2 (CHCH=N), 152.2 (CH=N).
(E)-syn-6b
1H NMR (CDCl3): = 0.18 (s, 9 H, OSiMe3), 5.68 (d, 1 H, NCCH,
3
3J = 16.2 Hz), 7.36 (d, 1 H, CH=N, J = 9.5 Hz), 7.62 (dd, 1 H,
14N NMR (acetone-d6): = 8.6 (NO2,
360 Hz), –126.0 (CN,
CHCH=N, 3J = 16.1, 3J = 9.4 Hz).
1/2
1300 Hz).
1/2
13C NMR (CDCl3): = 0.0 (OSiMe3),105.8 (NCCH), 117.8 (CN),
144.1 (CHCH=N),153.7 (CH=N).
Anal. Calcd for C7H10N2O4: C 45.16; H 5.41; N, 15.05. Found: C
45.41; H 5.42; N, 15.04.
(Z)-anti-6b
Silylation with Me3SiBr/Et3N, Enoximes 6a,b,e,i–k,o; General
Procedure
1H NMR (CDCl3): = 0.21 (s, 9 H, OSiMe3), 5.59 (d, 1 H, NCCH,
3J = 11.2 Hz), 6.94 (dd, 1 H, CHCH=N, J = 11.1, J = 10.8 Hz),
3
3
To a solution of nitro compound 1a,b,e,i–k,o (1.5 mmol) in CH2Cl2
(2 mL) at 0 °C (or at –28 °C for 1j,k) was added successively Et3N
(0.84 mL, 6.0 mmol) and Me3SiBr (0.70 mL, 5.3 mmol). The reac-
tion mixture was stirred (time and temperature is indicated in
Table 1) and petroleum ether (15 mL) was added. The resulting sus-
pension was poured into H2O (10 mL)–petroleum ether (20 mL)
mixture, the organic phase was separated and washed with an aq so-
lution of NaHSO4 H2O (100 mg in 20 mL), H2O, brine, dried
(Na2SO4), and concentrated in vacuum to give crude the enoximes
6a,b,e,i–k,o. The products 6a,e,j,k were distilled in a short-path dis-
8.25 (d, 1 H, CH=N, 3J = 10.6 Hz).
13C NMR (CDCl3): = 0.1 (OSiMe3), 102.9 (NCCH), 116.8 (CN),
143.2 (CHCH=N), 151.5 (CH=N).
14N NMR (for three isomers): = 12.5 (CN,
430 Hz).
1/2
Ethyl 2-Methyl-4-{[(Trimethylsilyl)oxy]imino}but-2-enoate
(6e)
(E)-syn-6e:(E)-anti-6e = 1:2.2; bp 64–68 °C/0.08 Torr.
1
tillation apparatus. The yields of 6b,i,o were determined by H
(E)-anti-6e
1H NMR (CDCl3):
= 0.23 (s, 9 H, OSiMe3), 1.29 (t, 3 H,
NMR spectra with internal standard (ClCH2CH2Cl) (Table 1).
OCH2CH3, 3J = 6.7 Hz), 1.98 (s, 3 H, Me), 4.20 (q, 2 H, OCH2Me,
3J = 6.7 Hz), 7.20 (d, 1 H, CH=CHN, J = 10.7 Hz), 8.16 (d, 1 H,
3
Methyl 4-{[(Trimethylsilyl)oxy]imino}but-2-enoate (6a)
(E)-syn-6a:(E)-anti-6a:(Z)-anti-6a = 1:4:1.3; bp 45–50 °C/4 Torr.
CH=N, 3J = 10.7 Hz).
The irradiation of CH=N signal at 8.16 ppm led to an enhancement
of the Me signal at 1.98 ppm.
13C NMR (CDCl3): = –0.7 (OSiMe3), 13.2 (OCH2Me), 14.4 (Me),
61.1 (OCH2Me), 131.1 (CHCH=N), 133.8 (CH=C), 151.7 (CH=N),
167.5 (C=O).
(E)-anti-6a
1H NMR (CDCl3): = 0.27 (s, 9 H, OSiMe3), 3.78 (s, 3 H, OMe),
6.15 (d, 1 H, MeO2CCH, 3J = 16.2 Hz), 7.37 (d, 1 H, CHCH=N,
3J = 16.2, 3J = 10.3 Hz), 7.93 (d, 1 H, CH=N, 3J = 10.3 Hz).
13C NMR (CDCl3):
(MeO2CCH), 138.0 (CHCH=N), 152.9 (CH=N), 166.1 (C=O).
= –1.1 (OSiMe3), 51.6 (OMe), 126.4
29Si NMR (CDCl3): = 27.55 (NOSiMe3).
29Si NMR (CDCl3): = 28.25 (NOSiMe3).
(E)-syn-6e
1H NMR (CDCl3): = 0.23 (s, 9 H, OSiMe3), 1.30 (t, 3 H, OCH2Me,
3J = 6.8 Hz), 2.02 (s, 3 H, Me), 4.22 (q, 2 H, OCH2Me, 3J = 6.6 Hz),
7.62 (d, 1 H, CH=N, 3J = 9.7 Hz), 7.67 (d, 1 H, CH=CHN, 3J = 9.4
Hz).
(E)-syn-6a
1H NMR (CDCl3): = 0.27 (s, 9 H, OSiMe3), 3.80 (s, 3 H, OMe),
6.17 (d, 1 H, MeO2CCH, 3J = 17.1 Hz), 7.42 (d, 1 H, CH=N,
3J = 10.2 Hz), 7.86 (dd, 1 H, CHCH=N, 3J = 17.2, 3J = 10.2 Hz).
The irradiation of CH=N signal at 7.62 ppm leads to an enhance-
ment of the CH3 signal at 2.02 ppm.
13C NMR (CDCl3): = –0.6 (OSiMe3), 13.3 (OCH2Me), 14.4 (Me),
61.2 (OCH2Me), 123.4 (CHCH=N), 135.0 (CH=C), 148.0 (CH=N),
167.9 (C=O).
13C NMR (CDCl3):
(MeO2CCH), 130.0 (CHCH=N), 149.6 (CH=N), 166.1 (C=O).
29Si NMR (CDCl3): = 27.78 (NOSiMe3).
= –1.1 (OSiMe3), 51.8 (OMe), 127.2
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of , -Unsaturated Oximes from Nitro Compounds
641
29Si NMR (CDCl3): = 27.9 (NOSiMe3).
Methyl 4-Oxo-4-phenyl-2-{[(trimethylsilyl)oxy]iminometh-
yl}but-2-enoate (6o)
(E)-anti-6o:(Z)-anti-6o = 1:1.
Anal. Calcd for C10H19NO3Si: C 52.37; H 8.35; N 6.11; Si 12.25.
Found: C 52.20; H 8.46; N 6.01; Si 12.51.
(Z)-anti-6o
Methyl 4-Phenyl-4-{[(trimethylsilyl)oxy]imino}but-2-enoate
1H NMR (CDCl3): = 0.20 (s, 9 H, OSiMe3), 3.80 (s, 3 H, OMe),
7.16 (s, 1 H, CH=C), 7.40 (m, 3 H, CHPh), 7.88 (m, 2 H, CHPh), 7.99
(s, 1 H, CH=N).
(6i)
This compound was subjected to desilylation without NMR control.
Dimethyl 4-[(Trimethylsilyl)oxy]iminohept-2-enedioate (6j)
The irradiation of CH= signal at 7.16 ppm leads to the enhancement
of CH=N signal at 7.99 ppm.
(E)-syn-6j:(E)-anti-6j = 1:7.6; bp 112–114 °C/0.2 Torr.
13C NMR (CDCl3): = –1.0 (OSiMe3), 52.5 (OMe), 127.5 (CH=C),
128.4, 128.7, 133.5 (CHPh), 135.6 and 141.0 (CH=C and CPh), 151.3
(CH=N), 165.2 (CO2Me), 192.6 (COPh).
29Si NMR (CDCl3): = 28.33 (NOSiMe3).
15N NMR (CDCl3): = 16.1 (d, CH=N, 2J = 2.5 Hz).
(E)-anti-6j
1H NMR (CDCl3):
= 0.25 (s, 9 H, OSiMe3), 2.49 (t, 2 H,
3
3
CH2CH2CO2Me, J = 7.4 Hz), 2.82 (t, 2 H, CH2CO2Me, J = 7.8
Hz), 3.70 (s, 3 H) and 3.80 (s, 3 H) (2 OMe), 6.25 (d, 1 H,
CHCO2Me, 3J = 16.8 Hz), 7.34 (d, 1 H, CH=CHCO2Me, 3J = 16.7
Hz).
13C NMR (CDCl3): = –0.9 (OSiMe3), 20.1 (CH2CH2CO2Me), 30.3
(E)-anti-6o
(CH2CO2Me), 51.7 (2
OMe), 122.1 (CHCO2Me), 141.1
1H NMR (CDCl3): = –0.09 (s, 9 H, OSiMe3), 3.80 (s, 3 H, OMe),
7.40 (m, 3 H, CH=C + CHPh), 7.52 (m, 1 H, CHPh), 7.88 (m, 2 H,
CHPh), 8.19 (s, 1 H, CH=N).
(CH=CHCO2Me), 160.6 (C=N), 166.5 and 172.6 (2 C=O).
29Si NMR (CDCl3): = 27.89 (NOSiMe3).
13C NMR (CDCl3): = –1.3 (OSiMe3), 52.2 (OMe), 128.6, 128.7,
133.6 (CHPh), 131.1 and 136.6 (CH=C and CPh), 136.8 (CH=C),
147.6 (CH=N), 166.1 (CO2Me), 188.4 (COPh).
29Si NMR (CDCl3): = 29.64 (NOSiMe3).
15N NMR (CDCl3): = 9.1 (d, CH = N, 2J = 3.0 Hz).
(E)-syn-6j
1H NMR (CDCl3):
= 0.17 (s, 9 H, OSiMe3), 2.51 (t, 2 H,
3
3
CH2CH2CO2Me, J = 8.7 Hz), 2.84 (t, 2 H, CH2CO2Me, J = 8.2
Hz), 3.71 and 3.81 (2 s, 2 3 H, 2 OMe), 6.26 (d, 1 H,
CHCO2Me, 3J = 16.1 Hz), 7.95 (d, 1 H, CH = CHCO2Me, 3J = 16.0
Hz).
Silylation with Me3SiOT/Et3N, Enoximes 6d–f,h,m,n; General
Procedure
13C NMR (CDCl3): = –0.9 (OSiMe3), 25.8 (CH2CH2CO2Me), 28.6
(CH2CO2Me), 51.8 and 51.9 (2 OMe), 124.0 (CHCO2Me), 131.0
(CH=CHCO2Me), 155.0 (C=N), 166.7 and 172.0 (2 C=O).
To a solution of the nitro compound 1d–f,m,n (1.5 mmol) in CH2Cl2
(2 mL) at 0 °C (or at –28 °C for 1h) was added Et3N (0.84 mL, 6.0
mmol) and Me3SiOTf (1.01 mL, 5.3 mmol). The reaction mixture
was stirred (time and temperature are indicated in Table 1), cooled
down to –30 °C and petroleum ether (15 mL) was added dropwise
to maintain a low temperature. Then MeOH (100 L) was added
and the mixture was stirred for an additional 10 min at the same
temperature. The resulting emulsion was poured into H2O (10 mL)–
petroleum ether (20 mL) mixture, the organic phase was separated
and washed with an aq solution of NaHSO4 H2O(100 mg in 20 mL),
H2O, brine, dried (Na2SO4), and concentrated in vacuum to give the
crude enoximes 6d–f,m,n. The product 6e was distilled in a short-
path apparatus. The yields of 6d,f,m,n were determined by 1H NMR
spectra with an internal standard (ClCH2CH2Cl) (Table 1).
29Si NMR (CDCl3): = 27.07 (NOSiMe3).
Anal. Calcd for C12H21NO5Si: C 50.15; H 7.37; N 4.87; Si 9.77.
Found: C 50.11; H 7.30; N 4.79; Si 9.98.
Dimethyl 2-(2-[(Trimethylsilyl)oxy]iminoethylidene)malonate
(6k)
syn-6k:anti-6k = 1:2.7; bp 112–114 °C/0.2 Torr.
anti-6k
1H NMR (CDCl3): = 0.19 (s, 9 H, OSiMe3), 3.77 and 3.80 (2 s,
2
3 H, 2 OMe), 7.33 (d, 1 H, CH=C, 3J = 10.6 Hz), 8.14 (d, 1 H,
CH=N, 3J = 10.6 Hz).
13C NMR (CDCl3): = –0.6 (OSiMe3), 52.9 and 53.0 (2 OMe),
130.1 (CH=C), 138.8 (CH=C), 151.7 (CH=N), 164.4 and 164.7 (2
C=O).
29Si NMR (CDCl3): = 20.23 (NOSiMe3).
15N NMR (CDCl3): = 26.5 (d, CH=N, 2J = 4.5 Hz).
4-[(Trimethylsilyl)oxy]penta-2,4-dienal O-(Trimethylsi-
lyl)oxime (6d)
(E)-syn-6d:(E)-anti-6d = 1:3.3.
(E)-anti-6d
1H NMR (CDCl3): = 0.23 and 0.25 (2 s, 2 9 H, 2 OSiMe3),
4.47 (s, 2 H, CH2=C), 6.26 (d, 1 H, CH=CHCH=N, 3J = 15.4 Hz),
syn-6k
3
3
5
6.51 (ddt, 1 H, CH=CHCH=N, J = 10.2, J = 15.3, J = 0.6 Hz),
7.86 (dd, 1 H, CH=N, 3J = 10.2, 4J = 0.4 Hz).
1H NMR (CDCl3): = 0.20 (s, 9 H, OSiMe3), 3.65 and 3.81 (2 s,
2
3 H, 2 OMe), 7.69 (d, 1 H, CH=N, 3J = 9.8 Hz), 7.79 (d, 1 H,
13C NMR (CDCl3): = –0.7 and 0.1 (2 OSiMe3), 98.7 (CH2=C),
123.3 (CH=CHCH=N), 136.1 (CH=CHCH=N), 154.5 (CH2=C),
154.8 (CH=N).
CH=C, 3J = 9.8 Hz).
13C NMR (CDCl3): = 0.5 (OSiMe3), 53.0 and 53.2 (2 OMe),
128.7 (CH=C), 131.0 (CH=C), 146.9 (CH=N), 164.7 and 164.8 (2
C=O).
29Si NMR (CDCl3): = 19.58 (COSiMe3), 25.62 (NOSiMe3).
29Si NMR (CDCl3): = 19.72 (NOSiMe3).
15N NMR (CDCl3): = 12.2 (d, CH=N, 2J = 13.5 Hz).
(E)-syn-6d
1H NMR (CDCl3): = 0.20 and 0.21 (2 s, 2 9 H, 2 OSiMe3),
4.54 (s, 2 H, CH2=C), 6.32 (d, 1 H, CH=CHCH=N, 3J = 15.4 Hz),
7.09 (dd, 1 H, CH=CHCH=N, 3J = 9.4, 3J = 15.3 Hz), 7.30 (d, 1 H,
CH=N, 3J = 9.5 Hz).
Anal. Calcd for C10H17NO5Si: C 46.31; H 6.61; N 5.40; Si 10.83.
Found: C 46.11; H 6.50; N 5.30; Si 11.02.
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

642
V. M. Danilenko et al.
PAPER
13C NMR (CDCl3): = –0.9 and –0.2 (2 OSiMe3), 100.5 (CH2=C),
117.4 (CH=CHCH=N), 136.7 (CH=CHCH=N), 151.8 (CH=N),
154.4 (CH2=C).
Dimethyl2-{[(Trimethylsilyl)oxy]iminomethyl}but-2-enedioate
(6l)
(Z)-anti-6l:(E)-anti-6l = 7:3; bp 82–84 °C/0.2 Torr.
29Si NMR (CDCl3): = 19.46 (COSiMe3), 25.24 (NOSiMe3).
(Z)-anti-6l
1H NMR (CDCl3): = 0.13 (s, 9 H SiMe3), 3.71 and 3.80 (2 s, 2
3 H, 2 OMe), 6.25 (s, 1 H, CH=C), 8.01 (s, 1 H, CH=N).
13C NMR (CDCl3): = –0.9 (OSiMe3), 52.2 and 52.3 (2 OMe),
124.0 (CH=C), 143.9 (CH=C), 152.9 (CH=N), 166.1 and 169.5 (2
C=O).
Ethyl 3-Methyl-4-[(trimethylsilyl)oxy]iminobut-2-enoate (6f)
This compound was subjected to desilylation without NMR control.
Methyl 4-[(Trimethylsilyl)oxy]imino-3-phenylbut-2-enoate (6h)
(E)-anti-6h:(Z)-anti-6h = 5:4.
29Si NMR (CDCl3): = 29.58 (OSiMe3).
15N NMR (CDCl3): = 15.4 (d, CH=N, 2J = 2.3 Hz).
(E)-anti-6h
1H NMR (CDCl3): = 0.14 (s, 9 H, OSiMe3), 3.58 (s, 3 H, OMe),
6.18 (s, 1 H, MeO2CCH), 7.20–7.43 (m, 5 H, C6H5), 7.80 (s, 1 H,
CH=N).
(E)-anti-6l
1H NMR (CDCl3): = 0.20 (s, 9 H, OSiMe3), 3.76 and 3.79 (2 s,
13C NMR (CDCl3): = 0.8 (SiMe3), 51.5 (OMe), 123.2 (C=CH),
127.4, 127.8 and 129.0 (CHPh), 134.7 (CPh), 149.3 (CH=C), 155.7
(CH=N), 165.7 (C=O).
2
3 H, 2 OMe), 6.50 (d, 1 H, CH=C, 4J = 0.8 Hz), 8.69 (d, 1 H,
CH=N, 4J = 0.8 Hz).
13C NMR: = –0.9 (OSiMe3), 52.7 and 52.6 (2 OMe), 126.6
(CH=C), 139.8 (CH=C), 149.4 (CH=N), 165.4 and 165.8 (2
C=O).
29Si NMR (CDCl3): = 28.80 (NOSiMe3).
15N NMR (CDCl3): = 15.6 (d, CH=N, 2J = 2.2 Hz).
29Si NMR (CDCl3): = 28.19 (NOSiMe3).
(E)-syn-6h
1H NMR (CDCl3): = 0.17 (s, 9 H, OSiMe3), 3.75 (s, 3 H, OMe),
6.14 (s, MeO2CCH), 7.20–7.43 (m, 5 H, C6H5), 9.25 (s, 1 H,
CH=N).
Anal. Calcd for C10H17NO5Si: C 46.31; H 6.61; N 5.40; Si 10.83.
Found: C 46.33; H 6.56; N 5.41; Si 10.82.
13C NMR (CDCl3): = 0.9 (SiMe3), 51.7 (OMe), 122.0 (C=CH),
128.2, 128.8, 129.2 (CHPh), 137.7 (CPh), 149.8 (CH=C), 152.5
(CH=N), 169.2 (C=O).
Dimethyl 2-[(Trimethylsilyl)oxy]ethanimidoylbut-2-enedioate
(6p)
(Z)-anti-6p:(E)-anti-6p = 17:3; bp 88-90 °C/0.2 Torr.
29Si NMR (CDCl3): = 27.55 (NOSiMe3).
Dimethyl 4-[(Trimethylsilyl)oxy]iminopent-2-enedioate (6m)
This compound was subjected to desilylation without NMR control.
(Z)-anti-6p
1H NMR (CDCl3): = 0.20 (s, 9 H, OSiMe3), 2.00 (s, 3 H, Me), 3.70
and 3.72 (2 s, 2 3 H, 2 OMe), 6.10 (s, 1 H, CH=C).
Methyl 4-Cyano-2-[(trimethylsilyl)oxy]iminobut-3-enoate (6n)
13C NMR (CDCl3): = –0.7 (OSiMe3), 9.5 Me, 52.0 and 52.1 (2
OMe), 120.0 (CH=C), 147.8 (CH=C), 157.9 (C=N), 165.4 and
166.4 (2 C=O).
29Si NMR (CDCl3): = 28.39 (NOSiMe3).
15N NMR (CDCl3): = 12.1 (d, CH=N, 3J = 4.5 Hz).
This compound was subjected to desilylation without NMR control.
Silylation with Me3SiCl/Et3N, Enoximes 6c,l,p–u; General Pro-
cedure
To a solution of Me3SiCl (0.76 mL, 6.0 mmol) in CCl4 (3 mL) at
0 °C was added Et3N (0.84 mL, 6.0 mmol) and the nitro compound
1c,l,p–u (1.5 mmol) in CCl4 (1.5 mL). The reaction mixture was
stirred at 20 °C for 1 h. The Et3N HCl formed was filtered off under
argon and washed with CCl4 (2 5 mL). The mother liquor was
evaporated in vacuum and the resulting crude enoximes 6c,l,p–u
were distilled in a short-path apparatus (Table 1).
(E)-anti-6p
1H NMR (CDCl3): = 0.17 (s, 9 H, OSiMe3), 2.00 (s, 3 H, Me), 3.67
and 3.79 (2 s, 2 3 H, 2 OMe), 6.82 (s, 1 H, CH=C).
13C NMR (CDCl3): = –0.4 (OSiMe3), 15.1 Me, 51.9 and 52.2 (2
OMe), 131.7 (CH=C), 140.8 (CH=C), 157.4 (C=N), 165.3 and
165.4 (2 C=O).
29Si NMR (CDCl3): = 25.27 (NOSiMe3).
15N NMR (CDCl3): = 12.1 (d, CH = N, 3J = 4.5 Hz).
3-Nitroprop-2-enal O-(Trimethylsilyl)oxime (6c)
Pure (E)-anti-6c; bp 48–50 °C/0.02 Torr.
1H NMR (CDCl3): = 0.27 (s, 9 H, OSiMe3), 7.30 (dd, 1 H, CHNO2,
3J = 13.5, 4J = 0.5 Hz), 7.67 (dd, 1 H, CH=CHNO2, 3J = 13.5, 3J =
10.3 Hz), 7.97 (dd, 1 H, CH=N, 3J = 10.4, 3J = 0.5 Hz).
13C NMR (CDCl3): = –0.9 (OSiMe3), 132.7 (CH = CHNO2), 142.8
(br, CHNO2), 148.5 (CH = N).
29Si NMR (CDCl3): = 30.55 (NOSiMe3).
Anal. Calcd for C11H19NO5Si: C 48.33; H 7.01; N 5.12; Si 10.27.
Found: C 48.49; H 6.99; N 5.29; Si 10.10.
Dimethyl 2-Methyl-3-{[(trimethylsilyl)oxy]iminomethyl}but-2-
enedioate (6q)
(E)-anti-6q:(Z)-anti-6q = 2:1; bp 80–95 °C/0.2 Torr.
14N NMR (CDCl3): = –12.0 (NO2,
170 Hz).
1/2
15N NMR (CDCl3): =1.9 (d, NO2, J = 7.1 Hz), 28.3 (d, CH=N,
2
(Z)-anti-6q
2J = 2.4 Hz).
1H NMR (CD3CN): = 0.18 (s, 9 H, OSiMe3), 1.98 (s, 3 H, Me),
3.77 and 3.79 (2 s, 2 3 H, 2 OMe), 8.49 (s, 1 H, CH=N).
Anal. Calcd for C6H12N2O3Si: C 38.28; H 6.42; N 14.88; Si 14.92.
Found: C 38.19; H 6.35; N 14.86; Si 15.01.
13C NMR (CD3CN): = –0.9 (OSiMe3), 17.7 Me, 52.7 and 53.0 (2
OMe), 134.0 (C=CMe), 136.4 (C=CMe), 151.7 (CH=N), 167.3
and 167.6 (2 C=O).
29Si NMR (CD3CN): = 28.38 (NOSiMe3).
15N NMR (CD3CN): = 7.0 (d, CH=N, 2J = 3.0 Hz).
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of , -Unsaturated Oximes from Nitro Compounds
643
(E)-anti-6q
13C NMR (CDCl3): = –1.5 (OSiMe3), 13.2 (Me), 52.3 (OMe),
108.0 (CH=C), 114.2 (CN), 146.8 (C=CH), 154.4 (C=N), 162.9
(C=O).
1H NMR (CD3CN): = 0.20 (s, 9 H, OSiMe3), 2.06 (s, 3 H, Me),
3.73 and 3.74 (2 s, 2 3 H, 2 OMe), 8.20 (s, 1 H, CH=C).
13C NMR (CD3CN): = –0.9 (OSiMe3), 14.9 (Me), 52.6 and 53.0 (2
OMe), 133.8 (C=CMe), 135.9 (C=CMe), 150.9 (CH=N), 167.4
and 167.8 (2 C=O).
29Si NMR (CD3CN): = 28.80 (NOSiMe3).
15N NMR (CD3CN): = 11.4 (d, CH=N, 2J = 3.1 Hz).
29Si NMR (CDCl3): = 28.34 (NOSiMe3).
15N NMR (CDCl3): = –12.2 (s, CH=N).
Anal. Calcd for C10H16N2O3Si: C 49.98; H 6.71; N 11.66; Si 11.69.
Found: C 49.54; H 6.50; N 11.39; Si 11.75.
Silylation with BSA, Enoximes 6c,l,o,p,r–u; General Procedure
To a solution of the nitro compound 1c,l,o,p,r–u (1.5 mmol) in CCl4
(3 mL) at 0 °C was added BSA (1.48 mL, 6.0 mmol). The reaction
mixture was stirred at 20 °C for 1 h (TLC control is recommended
since the rate of silylation depends on BSA purity). The volatile
components were evaporated at 50–60 °C/0.02 Torr and the result-
ing crude enoximes 6c,l,o,p,r–u were distilled in a short-path ap-
paratus (Table 1).
Anal. Calcd for C11H19NO5Si: C 48.33; H 7.01; N 5.12; Si 10.27.
Found: C 48.15; H 6.95; N 5.09; Si 10.10.
Trimethyl 2-{Phenyl[(trimethylsilyl)oxy]iminomethyl}but-2-
enedioate (6r)
(Z)-anti-6r:(E)-anti-6r = 4:1; bp 125–128 °C/0.2 Torr.
(Z)-anti-6r
1H NMR (CDCl3): = 0.22 (s, 9 H, OSiMe3), 3.69 and 3.89 (2 s,
Trimethylsilyl Ether of aci-Ethyl 3-Methyl-4-nitrobutanoate
(3f)
3
3 H, 2 OMe), 5.72 (s, 1 H, CH=C), 7.20–7.50 (m, 5 H, C6H5).
13C NMR (CDCl3): = –0.7 (OSiMe3), 52.4 and 52.9 (2 OMe),
123.1 (CH=C), 128.2–133.5 (C6H5), 148.3 (CH=C), 160.2 (C=N),
165.2 and 166.5 (2 C=O).
To a stirred solution of ethyl 3-methyl-4-nitrobutanoate (1f; 175
mg, 1 mmol) at 0 °C was added DBU (0.16 mL, 1.1 mmol). The
mixture was maintained at 0 °C for 40 min, and TMSCl (0.15 mL,
1.2 mmol) was added. The ice bath was removed, the mixture was
stirred at r.t. for 10 min and evaporated. The residue was treated
with anhyd benzene (10 mL) and filtered under argon. The mother
liquor was evaporated to give the silyl nitronate 3f (240 mg, 97%,
purity >95% by 1H NMR spectroscopy).
(E)-anti-6r
1H NMR (CDCl3): = 0.21 (s, 9 H, OSiMe3), 3.80 and 3.85 (2 s,
3
3 H, 2 OMe), 5.67 (s, 1 H, CH=C), 7.20–7.50 (m, 5 H, C6H5).
13C NMR (CDCl3): = –0.5 (OSiMe3), 52.7 and 53.0 (2 OMe),
122.0 (CH=C), 128.2–133.5 (C6H5), 148.5 (CH=C), 156.0 (C=N),
165.7 (C=O), 165.8 (C=O).
1H NMR (CDCl3): = 0.31 (s, 9 H, SiMe3), 1.17 (d, 3 H, Me,
3
3J = 6.6 Hz), 1.26 (t, 3 H, OCH2Me, J = 7.4 Hz), 2.43 (dd, 1 H,
CH2C=O, 3J = 15.5 Hz, 3J = 7.4 Hz), 2.58 (dd, 1 H, CH2C=O,
Anal. Calcd for C16H21NO5Si: C 57.29; H 6.31; N 4.18; Si 8.37.
Found: C 57.14; H 6.20; N 4.09; Si 8.55.
3
3J = 15.5 Hz, J = 5.9 Hz), 3.09 (m, 1 H, CHMe), 4.13 (q, 2 H,
OCH2, 3J = 7.4 Hz), 6.13 (d, 1 H, CH=N, 3J = 6.6 Hz).
13C NMR (CDCl3): = –0.2 (SiMe3), 14.2 (Me), 16.5 (Me), 28.6
(CH), 37.5 (CH2), 60.4 (OCH2), 119.8 (CH=N), 171.3 (C=O).
29Si NMR (CDCl3): = 26.39 (NOSiMe3).
Trimethyl 3-[(Trimethylsilyl)oxy]iminoprop-1-ene-1,2,3-tricar-
boxylate (6s)
Pure (Z)-anti-6s; bp 111–113 °C/0.2 Torr.
1H NMR (CD2Cl2): = 0.24 (s, 9 H, OSiMe3), 3.76 and 3.94 (2 s,
6 H, 9 H, 3 OMe), 6.10 (s, 1 H, CH=C).
14N NMR (CDCl3): = –91.6 (C=N,
1190 Hz).
1/2
13C NMR (CD2Cl2): = 0.0 (OSiMe3), 52.6, 52.8 and 53.0 (3
OMe), 122.7 (CH=C), 141.2 (CH=C), 153.4 (C=N), 162.0, 164.6
and 164.9 (C=O).
Ethyl 3-Methyl-4-(hydroxyimino)but-2-enoate (2f) from Tri-
methylsilyl Ether of aci-Ethyl 3-Methyl-4-nitrobutanoate (3f)
To a solution of silyl nitronate 3f (240 mg, 1 mmol) in CH2Cl2 (2
mL) at –30 °C was added Et3N (0.35 mL, 2.5 mmol) and Me3SiOTf
(0.43 mL, 2.3 mmol). The reaction mixture was stirred for 3 h at
–30 °C and petroleum ether (15 mL) was added dropwise to main-
tain the low temperature. Then MeOH (100 L) was added and the
mixture was stirred for an additional 10 min at the same tempera-
ture. The resulting emulsion was poured into H2O (10 mL)/petro-
leum ether (20 mL) mixture. The organic phase was separated and
washed with an aq solution of NaHSO4 H2O (100 mg in 20 mL),
H2O (10 mL), brine (2 10 mL), dried (Na2SO4), and concentrated
in vacuum. The crude enoxime 6f obtained was dissolved in MeOH
(1 mL) and NH4F (spatula tip) was added. After stirring at r.t. for 1
h, the solvent was removed in vacuum and the residue was subjected
to column chromatography (silica gel, EtOAc–hexane, 1: 5) to give
the enoxime 2f (94 mg, 60%) as white crystals; mp 75–80 °C (pe-
troleum ether–CH2Cl2).
Anal. Calcd for C12H19NO7Si: C 45.41; H 6.03; N 4.41; Si 8.85.
Found: C 45.36; H 6.00; N 4.45; Si 8.80.
Methyl 3-Cyano-2-{[(trimethylsilyl)oxy]iminomethyl}prop-2-
enoate (6t)
This compound was subjected to desilylation without NMR control.
Methyl 3-Cyano-2-{[(trimethylsilyl)oxy]iminomethyl}but-2-
enoate (6u)
(Z)-anti-6u:(E)-anti-6u = 1:1; bp 80–86 °C/0.1 Torr.
(Z)-anti-6u
1H NMR (CDCl3): = 0.22 (s, 9 H, OSiMe3), 2.02 (s, 3 H, Me), 3.88
(s, 3 H, OMe), 5.87 (s, 1 H, CH=C).
13C NMR (CDCl3): = –1.8 (OSiMe3), 9.4 (Me), 51.9 (OMe), 99.8
(CH=C), 114.1 (CN), 151.2 (C=CH), 155.5 (C=N), 163.7 (C=O).
Desilylation with MeOH/NH4F, Enoximes 2a–u; General Proce-
dure
The neat enoxime 6 (1 mmol) was dissolved in MeOH (5 mL) at
0 °C and NH4F (5 mg, 0.14 mmol) was added. After stirring for 5 h
at r.t., the solvent was evaporated in vacuum and the residue was
subjected to column chromatography (silica gel). The resulting
29Si NMR (CDCl3): = 29.53 (NOSiMe3).
15N NMR (CDCl3): = –0.1 (s, CH=N).
(E)-anti-6u
1H NMR (CDCl3): = 0.26 (s, 9 H, OSiMe3), 2.08 (s, 3 H, Me), 3.82
(s, 3 H, OMe), 6.39 (s, 1 H, CH=C).
enoximes
(Table 1).
2 were additionally purified by recrystallization
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

644
V. M. Danilenko et al.
PAPER
Methyl 4-(Hydroxyimino)but-2-enoate (2a)
(E)-syn-2a:(E)-anti-2a:(Z)-anti-2a = 1:4:1.3; mp 92–94 °C
(CH2Cl2–pentane).
13C NMR (CDCl3): = 133.5 (CH=CHNO2), 143.9 (CHNO2),
145.8 (CH=N).
14N NMR (CDCl3): = –9.4 (NO2,
52 Hz).
1/2
Anal. Calcd for C3H4N2O3: C 31.04; H 3.47; N 24.13. Found: C
31.35; H 3.54; N 23.96.
(E)-anti-2a
1H NMR (CDCl3): = 3.75 (s, 3 H, OMe), 6.16 (d, 1 H, CHCO2Me,
3J = 16.3), 7.34 (dd, 1 H, CHCH=N, 3J = 16.3, 3J = 10.3 Hz), 7.87
(d, 1 H, CH=N, 3J = 10.3 Hz), 10.20 (br s, 1 H, OH).
4-Oxopent-2-enal Oxime (2d)
(E)-syn-2d:(E)-anti-2d = 1:8.5; mp 40–43 °C (CH2Cl2–C5H14).
13C NMR (CDCl3): = 52.0 (OMe), 126.0 (CHC2OMe), 138.4
(CHCH=N), 149.1 (CH=N), 166.8 (C=O).
(E)-anti-2d
1H NMR (CDCl3): = 2.34 (s, 3 H, Me), 6.38 (d, 1 H, CH=CHAc,
(E)-syn-2a
3
3
3J = 16.2 Hz), 7.16 (dd, 1 H, CH=CHAc, J = 16.2, J = 10.0 Hz),
1H NMR (CDCl3): = 3.76 (s, 3 H, OMe), 6.18 (d, 1 H, CHCO2Me,
7.88 (d, 1 H, CH=N, 3J = 9.9 Hz), 9.53 (br s, 1 H, OH).
3J = 16.1 Hz), 7.26 (d, 1 H, CH=N, J = 10.2 Hz), 7.84 (dd, 1 H,
3
13C NMR (CDCl3):
= 27.4 Me, 135.3 (CH=CHAc), 136.5
CHCH=N, 3J = 16.0, 3J = 10.2 Hz), 10.20 (br s, 1 H, OH).
(CH=CHAc), 150.0 (C=N), 198.7 (C=O).
13C NMR (CDCl3): = 52.0 (OMe), 127.2 (CHC2OMe), 129.9
(CHCH=N), 145.9 (CH=N), 166.8 (C=O).
(E)-syn-2d
1H NMR (CDCl3): = 2.38 (s, 3 H, Me), 6.34 (d, 1 H, CH=CHAc,
(Z)-anti-2a
3
3J = 16.4 Hz), 7.29 (d, 1 H, CH=N, J = 9.4 Hz), 7.67 (dd, 1 H,
1H NMR (CDCl3):
= 3.74 (s, 3 H, OMe), 6.01 (dd, 1 H,
CH=CHAc, 3J = 16.4, 3J = 9.4 Hz), 9.53 (br s, 1 H, OH).
CHCO2Me, 3J = 13.0, 4J = 1.0 Hz), 6.69 (dd, 1 H, CHCH=N,
3J = 13.0, 3J = 9.3 Hz), 8.88 (dd, 1 H, CH=N, 3J = 9.3, 4J = 1.0 Hz),
10.20 (br s, 1 H, OH).
13C NMR (CDCl3):
= 27.3 Me, 127.8 (CH=CHAc), 136.0
(CH=CHAc), 146.9 (C=N), 199.5 (C=O).
13C NMR (CDCl3): = 51.7 (OMe), 122.4 (CHCO2Me), 137.6
(CHCH=N), 148.5 (CH=N), 166.8 (C=O).
Ethyl 2-Methyl-4-(hydroxyimino)but-2-enoate (2e)
(E)-syn-2e:(E)-anti-2e = 1: 2; mp 68–74 °C (CH2Cl2–pentane).
Anal. Calcd for C5H7NO3: C 46.51; H 5.46; N 10.85. Found: C
46.79; H 5.26; N 10.97.
(E)-anti-2e
1H NMR (CDCl3): = 1.14 (t, 3 H, OCH2Me, 3J = 6.7 Hz), 1.85 (s,
3
Methyl 4-(Hydroxyimino)but-2-enenitrile (2b)
(E)-syn-2b:(E)-anti-2b:(Z)-anti-2b = 1:13:21; mp 100–125 °C
(CH2Cl2–cyclohexane).
3 H, Me), 4.06 (q, 2 H, OCH2Me, J = 6.6 Hz), 7.04 (d, 1 H,
CHCH=N, 3J = 10.7 Hz), 7.95 (d, 1 H, CH=N, 3J = 10.7 Hz), 8.95
(br s, 1 H, OH).
13C NMR (CDCl3):
(OCH2Me), 131.0 (CHCH=N), 133.2 (CH=C), 147.0 (CH=N),
167.2 (C=O).
= 14.7 (OCH2CH3), 29.9 (Me), 60.7
(E)-anti-2b
1H NMR (acetone-d6): = 5.99 (d, 1 H, NCCH, 3J = 16.0 Hz), 7.14
(dd, 1 H, CHCH=N, 3J = 10.0, 3J = 16.2 Hz), 7.96 (d, 1 H, CH=N,
3J = 10.2 Hz), 11.25 (br s, 1 H, OH).
(E)-syn-2e
1H NMR (CDCl3): = 1.17 (t, 3 H, OCH2CH3, 3J = 7.4 Hz), 1.88 (s,
3 H, Me), 4.08 (q, 2 H, OCH2Me, 3J = 7.4 Hz), 7.32 (d, 1 H, CH=N,
3J = 10.2 Hz), 7.56 (d, 1 H, CH=CHN, 3J = 10.1 Hz), 8.95 (br s, 1
H, OH).
13C NMR (acetone-d6): = 104.7 (NCCH), 117.9 (CN), 145.1
(CHCH=N), 149.2 (CH=N).
(E)-syn-2b
1H NMR (acetone-d6): = 6.07 (d, 1 H, NCCH, 3J = 16.2 Hz), 7.37
13C NMR (CDCl3):
= 11.7 (OCH2CH3), 29.4 (Me), 60.6
3
3
(d, 1 H, CH=N, J = 9.5 Hz), 7.64 (dd, 1 H, CHCH=N, J = 16.3,
(OCH2Me), 122.7 (CHCH=N), 135.6 (CH=C), 143.5 (CH=N),
167.5 (C=O).
3J = 9.5 Hz), 11.25 (br s, 1 H, OH).
13C NMR (acetone-d6): = 106.3 (NCCH), 117.9 (CN), 145.3
(CHCH=N), 160.2 (CH=N).
Anal. Calcd for C7H11NO3: C 53.49; H 7.05; N 8.91. Found: C
53.25; H 7.00; N 8.79.
(Z)-anti-2b
Ethyl 3-Methyl-4-(hydroxyimino)but-2-enoate (2f)
Pure (E)-anti-2f; mp 75–80 °C (CH2Cl2–pentane).
1H NMR (DMSO-d6): = 1.22 (t, 3 H, OCH2CH3, 3J = 7.1 Hz), 2.22
(d, 3 H, Me, 4J = 1.3 Hz), 4.12 (q, 2 H, OCH2, 3J = 7.1 Hz), 6.06 (br
s, 1 H, CHCO2Et), 7.87 (s, 1 H, CH=N), 11.70 (s, 1 H, OH).
1H NMR (acetone-d6): = 5.89 (d, 1 H, NCCH, 3J = 10.5 Hz), 7.05
(dd, 1 H, CHCH=N, 3J = 10.5, 3J = 10.4 Hz), 8.13 (d, 1 H, CH=N,
3J = 10.6 Hz).
13C NMR (acetone-d6): = 103.1 (NCCH), 115.9 (CN), 143.9
(CHCH=N), 147.5 (CH=N).
14N NMR (for three isomers, (acetone-d6): = –112.5 (CN,
The irradiation of CH=N signal at 7.87 ppm, EtO2CCH signal at
6.06 ppm and Me signal at 2.22 ppm led to an enhancement of
EtO2CCH signal at 6.06 ppm, CH=N signal at 7.87 ppm, and CH=N
signal at 7.87 ppm, respectively.
13C NMR (DMSO-d6): = 12.8 (CH3CH2O), 14.1 (Me), 59.6
(CH2O), 122.2 (CHCO2Et), 148.4 (C=CH), 151.5 (CH=N), 165.6
(C=O).
1/2
460 Hz), 21.2 (C=N,
1020 Hz).
1/2
Anal. Calcd for C4H4N2O: C 50.00; H 4.20; N 29.15. Found: C
50.14; H 4.26; N 29.47.
3-Nitroprop-2-enal Oxime (2c)
Pure (E)-anti-2c; mp 60–82 °C.
Anal. Calcd for C7H11NO3: C 53.49; H 7.05; N 8.91. Found: C
53.35; H 7.00; N 8.96.
1H NMR (acetone-d6): = 7.56 (dd, 1 H, CH=CHNO2, J = 13.5,
3
3J = 9.7 Hz), 7.67 (d, 1 H, CHNO2, J = 13.5 Hz), 8.08 (d, 1 H,
3
CH=N, 3J = 10.4 Hz), 11.07 (br s, 1 H, OH).
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of , -Unsaturated Oximes from Nitro Compounds
645
Methyl 4-(Hydroxyimino)-3-phenylbut-2-enoate (2h)
Dimethyl 2-(2-Hydroxyiminoethylidene)malonate (2k)
(E)-anti-2h:(Z)-anti-2h = 1:1.5; mp 179–181 °C [CH2Cl2, for 1:5.7
mixture (E)-anti-2h:(Z)-anti-2h] and 115–135 °C [CH2Cl2, for
1.9:1 mixture of (E)-anti-2h:(Z)-anti-2h].
syn-2k:anti-2k = 1:21; mp 83–85 °C (CH2Cl2–pentane).
anti-2k
1H NMR (CDCl3): = 3.83 and 3.86 (2 s, 2 3 H, 2 OMe), 7.41
(d, 1 H, CH=C, 3J = 10.5 Hz), 8.19 (d, 1 H, CH=N, 3J = 10.5 Hz),
9.02 (br s, 1 H, OH).
(E)-anti-2h
1H NMR (acetone-d6): = 3.52 (s, 3 H, OMe), 6.29 (s, 1 H, CH=C),
7.18–7.46 (m, 5 H, C6H5), 8.07 (s, 1 H, CH=N), 10.74 (s, 1 H, OH).
13C NMR (CDCl3): = 53.0 and 53.1 (2 OMe), 139.7 (CH=C),
138.6 (CH=C), 147.7 (CH=N), 164.0 and 164.6 (2 C=O).
The irradiation of CH= signal at 6.29 ppm leads to the enhancement
of CH=N signal at 8.07 ppm.
13C NMR (acetone-d6): = 51.3 (OMe), 123.7 (CH=C), 128.0,
128.3, 129.6 (CHPh), 136.2 (CPh), 150.5 (CH=C), 152.6 (CH=N),
165.9 (C=O).
Anal. Calcd for C7H9NO5: C 44.92; H 4.85; N 7.48. Found: C 44.75;
H 4.50; N 7.32.
Dimethyl 2-(Hydroxyiminomethyl)but-2-enedioate (2l)
(Z)-anti-2l:(E)-anti-2l = 7:3.
15N NMR (acetone-d6): = 18.8 (s, CH=N).
(Z)-anti-2l
Mp 142–143 °C (benzene).
1H NMR (acetone-d6): = 3.73 and 3.79 (2 s, 2 3 H, 2 OMe),
6.25 (d, 1 H, CH=C, 4J = 0.6 Hz), 7.97 (d, 1 H, CH=N, 4J = 0.6 Hz),
11.07 (br s, 1 H, OH).
13C NMR (acetone-d6):
(CH=C), 144.5 (CH=C), 147.9 (CH=N), 164.7 and 165.4 (2
C=O).
(Z)-anti-2h
1H NMR (acetone-d6): = 3.75 (s, 3 H, OMe), 6.10 (s, 1 H, CH=C),
7.18–7.46 (m, 5 H, C6H5), 9.22 (s, 1 H, CH=N), 10.90 (s, 1 H, OH).
The irradiation of CH= signal at 6.10 ppm leads to the enhancement
of C6H5 signal at 7.20 ppm.
13C NMR (acetone-d6): = 51.8 (OMe), 121.7 (CH=C), 128.6,
129.5, 129.9 (CHPh), 138.9 (CPh), 148.5 (CH=N), 151.2 (CH=C),
166.2 (C=O).
= 52.0 and 52.3 (2
OMe), 122.9
15N NMR (acetone-d6): = 13.2 (d, CH=N, 2J = 2.7 Hz).
15N NMR (acetone-d6): = 23.1 (d, CH=N, 2J = 4.8 Hz).
Anal. Calcd for C7H9NO5: C 44.92; H 4.85; N 7.48. Found C 45.00;
H 4.67; N 7.44.
Anal. Calcd for C11H11NO3: C 64.38; H 5.40; N 6.83. Found: C
64.04; H 5.38; N 6.65.
(E)-anti-2l
Mp 144–145 °C (benzene).
Methyl 4-Phenyl-4-(hydroximino)but-2-enoate (2i)
(E)-syn-2i:(E)-anti-2i = 10:9; mp 91–97 °C (CH2Cl2–pentane).
1H NMR (acetone-d6): = 3.77 and 3.79 (2 s, 2 3 H, 2 OMe),
6.40 (d, 1 H, CH=C, 4J = 0.9 Hz), 8.72 (d, 1 H, CH=N, 4J = 0.8 Hz),
11.13 (br s, 1 H, OH).
(E)-anti-2i
1H NMR (acetone-d6): = 3.69 (s, 3 H, OMe), 5.73 (d, 1 H,
3
3
CHCO2Me, J = 16.0 Hz), 8.08 (d, 1 H, CHC=N, J = 16.1 Hz),
7.28–7.53 (m, 5 H, C6H5), 11.12 (br s, 1 H, OH).
13C NMR (acetone-d6): = 51.9 (OMe), 126.8 (CHCO2Me), 129.3,
129.6, 129.3 (CHPh), 135.0 (CPh), 142.8 (CHC=N), 156.7 (C=N),
166.7 (C=O).
13C NMR (acetone-d6):
= 52.4 and 52.9 (2
OMe), 125.1
(CH=C), 141.4 (CH=C), 145.4 (CH=N), 166.6 and 166.0 (2
C=O).
15N NMR (acetone-d6): = 14.7 (d, CH=N, 2J = 2.5 Hz).
Anal. Calcd for C7H9NO5: C 44.92; H 4.85; N 7.48. Found: C 45.28;
H 4.92; N 7.46.
(E)-syn-2i
1H NMR (acetone-d6): = 3.75 (s, 3 H, OMe), 6.09 (d, 1 H,
3
Dimethyl 4-(Hydroxyimino)pent-2-enedioate (6m)
(E)-anti-2m:(E)-syn-2m = 3:1.
CHC2OMe, J = 16.1 Hz), 7.28–7.53 (m, 6 H, C6H5 + CHC=N),
11.30 (br s, 1 H, OH).
13C NMR (acetone-d6): = 51.6 (OMe), 124.0 (CHCO2Me), 128.8,
128.9, 129.0 (CHPh), 131.8 (CPh), 131.9 (CHC=N), 154.5 (C=N),
166.6 (C=O).
(E)-anti-2m
Mp 118–120 °C (hexane–CH2Cl2).
1H NMR (acetone-d6): = 3.76 and 3.81 (2 s, 2 3 H, 2 Me),
Anal. Calcd for C11H11NO3: C 64.38; H 5.40; N 6.83. Found: C
64.05; H 5.21; N 7.14.
3
6.90 (d, 1 H, CHCO2Me, J = 16.2 Hz), 7.67 (d, 1 H, CHC=N,
3J = 16.2 Hz), 12.38 (br s, 1 H, OH).
13C NMR (acetone-d6):
(CHCO2Me), 128.4 (CHC=N), 146.4 (C=N), 164.1 and 167.4 (2
C=O).
= 52.4 and 52.9 (2
MeO), 127.8
Dimethyl 4-(Hydroxyimino)hept-2-enedioate (2j)
(E)-syn-2j:(E)-anti-2j = 1:14; mp 66–67 °C (CH2Cl2–pentane).
(E)-anti-2j
3
1H NMR (CDCl3): = 2.53 (t, 2 H, CH2CH2CO2Me, J = 7.5 Hz),
(E)-syn-2m
1H NMR (acetone-d6): = 3.73 and 3.90 (2 s, 2 3 H, 2 Me),
2.82 (t, 2 H, CH2CO2Me, 3J = 7.4 Hz), 3.66 and 3.76 (2 s, 2 3 H,
3
3
6.06 (d, 1 H, CHCO2Me, J = 16.2 Hz), 7.19 (d, 1 H, CHC=N,
2
OMe), 6.24 (d, 1 H, CHCO2Me, J = 16.5 Hz), 7.29 (d, 1 H,
3J = 16.2 Hz), 11.75 (br s, 1 H, OH).
CH=CHCO2Me, 3J = 16.5 Hz).
13C NMR (acetone-d6): = 52.4 and 52.9 (2
(CHCO2Me), 136.5 (CHC=N), 151.2 (C=N), 166.7 and 167.4 (2
C=O).
OMe), 125.4
13C NMR (CDCl3): = 20.2 (CH2CH2CO2Me), 30.2 (CH2CO2Me),
52.1 and 52.2 (2
(CH=CHCO2Me), 157.1 (C=N), 167.0 and 171.1 (2 C=O).
Me), 122.3 (CHCO2Me), 140.7
Anal. Calcd for C7H9NO5: C 44.92; H 4.85; N 7.48. Found: C 45.04;
H 4.90; N 7.49.
Anal. Calcd for C9H13NO5: C 50.23; H 6.09; N 6.51. Found: C
50.20; H 6.00; N 6.47.
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

646
V. M. Danilenko et al.
PAPER
Methyl 4-Cyano-2-(hydroxyimino)but-3-enoate (2n)
(E)-anti-2n:(E)-syn-2n = 4:1; mp 139–141 °C (CH2Cl2).
13C NMR (acetone-d6): = 17.7 (Me), 52.4 and 52.7 (2 OMe),
131.2 (C=CMe), 137.7 (C=CMe), 147.1 (CH=N), 167.2 and 167.5
(2 C=O).
(E)-anti-2n
Anal. Calcd for C8H11NO5: C 47.76; H 5.51; N 6.96.Found: C
47.79; H 5.89; N 7.12.
1H NMR (acetone-d6): = 3.82 (s, 3 H, OMe), 6.75 (d, 1 H, CHCN,
3J = 16.5 Hz), 7.48 (d, 1 H, CHC=N, 3J = 16.5 Hz), 12.70 (br s, 1 H,
OH).
Dimethyl 2-(Phenyl[hydroxy]iminomethyl)but-2-enedioate (2r)
Pure (Z)-anti-2r; mp 128–129 °C (CCl4).
13C NMR (acetone-d6): = 52.6 (OMe), 107.8 (CHCN), 117.7
(CN), 133.5 (CHC=N), 150.5 (C=N), 163.3 (C=O).
(Z)-anti-2r
(E)-syn-2n
1H NMR (acetone-d6): = 3.69 and 3.88 (2 s, 2 3 H, 2 OMe),
5.65 (s, 1 H, CH=C), 7.35 (m, 3 H, C6H5), 7.50 (m, 2 H, C6H5),
11.40 (br s, 1 H, OH).
1H NMR (acetone-d6): = 3.88 (s, 3 H, OMe), 5.91 (d, 1 H, CHCN,
3J = 16.5 Hz), 7.18 (d, 1 H, CHC=N, 3J = 16.5 Hz), 12.01 (br s, 1 H,
OH).
13C NMR (acetone-d6):
= 52.3 and 52.6 (2
OMe), 122.1
13C NMR (acetone-d6): = 52.6 (OMe), 103.9 (CHCN), 117.1
(CN), 144.7 (CHC=N), 149.8 (C=N), 162.2 (C=O).
(CH=C), 129.5, 129.6, 130.2 (CHPh), 131.3 (CPh), 146.5 (CH=C),
156.1 (C=N), 165.4 and 165.8 (2 C=O).
Anal. Calcd for C6H6N2O3: C 46.76; H 3.92; N 18.18. Found: C
46.56; H 4.09; N 18.10.
Anal. Calcd for C13H13NO5: C 59.31; H 4.98; N 5.32. Found: C
59.19; H 5.05; N 5.39.
Methyl 4-Oxo-4-phenyl-2-(hydroxyiminomethyl)but-2-enoate
Trimethyl 3-(Hydroxyimino)prop-1-ene-1,2,3-tricarboxylate
(2o)
(2s)
Pure (E)-anti-2o; mp 124–126 °C.
Pure (Z)-anti-2s; mp 120–121 °C (Et2O).
1H NMR (acetone-d6): = 3.86 (s, 3 H, OMe), 7.16 (s, 1 H, CHBz),
(Z)-anti-2s
7.50 (m, 2 H, Hmeta, C6H5), 7.61 (m, 1 Hpara, C6H5), 7.94 (m, 2 Hortho
C6H5), 7.96 (s, 1 H, CH=N), 8.86 (br s, 1 H, OH).
,
1H NMR (acetone-d6): = 3.73, 3.77 and 3.90 (3 s, 3 3 H, 3
OMe), 6.03 (s, 1 H, CH=C), 12.15 (s, 1 H,OH).
The irradiation of CH=N signal at 7.96 ppm leads to the enhance-
ment of CHBz signal at 7.16 ppm.
13C NMR (CDCl3): = 51.8 (OMe), 127.0 (CH=C), 128.7, 129.2,
133.9 (CHPh), 137.5 and 142.7 (CH=C and CPh), 148.2 (CH=N),
166.2 (CO2Me), 188.4 (COPh).
13C NMR (acetone-d6): = 52.5, 52.8 and 53.1 (3 OMe), 122.2
(CH=C), 142.1 (CH=C), 149.8 (C=N), 162.5, 164.8 and 165.1 (3
C=O).
Anal. Calcd for C9H11NO7: C 44.09; H 4.52; N 5.71. Found: C
44.19; H 4.56; N 5.84.
Anal. Calcd for C12H11NO4: C 61.80; H 4.75; N 6.01. Found: C
61.60; H 4.51; N 5.83.
Methyl 3-Cyano-2-(hydroxyiminomethyl)prop-2-enoate (2t)
(Z)-anti-2t:(E)-anti-2t = 1:4; mp 95–96 °C.
Dimethyl 2-(Hydroxyethanimidoyl)but-2-enedioate (2p)
Pure (Z)-anti-2p; mp 132–133 °C (benzene).
(Z)-anti-2t
1H NMR (acetone-d6): = 3.89 (s, 3 H, OMe), 6.35 (s, 1 H, CH=C),
8.02 (s, 1 H, CH=N), 11.43 (br s, 1 H, OH).
(Z)-anti-2p
1H NMR (DMSO-d6): = 1.96 (s, 3 H, Me), 3.68 and 3.71 (2 s, 2
3 H, 2 OMe), 6.24 (s, 1 H, CH=C), 11.32 (br s, 1 H, OH).
13C NMR (acetone-d6): = 53.4 (OMe), 104.3 (CH=C), 115.9 (CN),
146.0 (CH=N), 146.9 (C=CH), 164.3 (C=O).
13C NMR (DMSO-d6): = 7.4 Me, 50.5 and 50.9 (2 OMe), 117.2
(CH=C), 146.9 (CH=C), 151.6 (C=N), 164.7 and 166.9 (2 C=O).
(E)-anti-2t
1H NMR (acetone-d6): = 3.86 (s, 3 H, OMe), 6.48 (s, 1 H, CH=C),
8.08 (s, 1 H, CH=N), 11.43 (br s, 1 H, OH).
Anal. Calcd for C8H11NO5: C 47.76; H 5.51; N 6.96. Found: C
47.80; H 5.51; N 7.06.
13C NMR (acetone-d6): = 53.6 (OMe), 106.5 (CH=C), 116.1 (CN),
143.4 (C=CH), 143.9 (CH=N), 164.6 (C=O).
Dimethyl 2-Methyl-3-(hydroxyiminomethyl)but-2-enedioate
(2q)
(E)-anti-2q:(Z)-anti-2q = 2:1.
Anal. Calcd for C6H6N2O3: C 46.76; H 3.92; N 18.18.Found: C
46.64; H 3.91; N 18.17.
(Z)-anti-2q
Mp 113–114 °C (benzene).
1H NMR (acetone-d6): = 2.09 (s, 3 H, Me), 3.72 and 3.73 (2 s, 2
3 H, 2 OMe), 8.17 (s, 1 H, CH=N), 11.09 (s, 1 H, OH).
13C NMR (acetone-d6): = 14.3 (Me), 52.3 and 52.7 (2 OMe),
131.6 (C=CMe), 137.2 (C=CMe), 146.3 (CH=N), 167.3 and 167.5
(2 C=O).
Methyl 3-Cyano-2-(hydroxyiminomethyl)but-2-enoate (2u)
Pure (Z)-anti-2u; mp 97–99 °C (CHCl3–cyclohexane).
1H NMR (acetone-d6): = 2.04 (s, 3 H, Me), 3.83 (s, 3 H, OMe),
6.12 (s, 1 H, CH=C).
13C NMR (acetone-d6): = 9.6 Me, 53.1 (OMe), 100.2 (CH=C),
116.1 (CN), 152.7 (C=N), 153.3 (C=CH), 165.7 (C=O).
Anal. Calcd for C7H8N2O3: C 50.00; H 4.80; N 16.66. Found: C
50.08; H 4.87; N 16.43.
Anal. Calcd for C8H11NO5: C 47.76; H 5.51; N 6.96. Found: C
47.97; H 5.68; N 7.09.
(E)-anti-2q
Mp 93–94 °C (benzene).
Acknowledgement
This work was performed at the Scientific Educational Center for
young chemists and supported by Russian Foundation for Basic Re-
1H NMR (acetone-d6): = 1.96 (s, 3 H, Me), 3.78 and 3.81 (2 s, 2
3 H, 2 OMe), 8.51 (s, 1 H, CH=C), 10.84 (s, 1 H, OH).
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of , -Unsaturated Oximes from Nitro Compounds
647
search (grants ## 98-03-33002, 99-03-32015 and 96-15-97332) and
Federal Program «Integration» (project # A0082).
Furihata, K.; Hayakawa, Y.; Seto, H. J. Org. Chem. 1999,
64, 153. (d) Suzumura, K.; Takahashi, I.; Matsumoto, H.;
Nagai, K.; Setiawan, B.; Rantiatmodjo, R. M.; Suzuki, K.;
Nagano, N. Tetrahedron Lett. 1997, 63, 7573.
(16) Franchetti, P.; Grifantini, M.; Martelli, S. J. Med. Chem.
1975, 18, 839.
(17) Several approachs to conjugated enoximes have been
described: (a) VanEijk, P. J. S. S.; Reinhoudt, D. N.;
Harkema, S.; Visser, R. Recl. Trav. Chim. Pays-Bas 1986,
105 , 103. (b) Severin, Th.; Bruck, B. Chem. Ber. 1965, 98,
3847. (c) Lerche, H.; Treiber, J.; Severin, Th. Chem. Ber.
1980, 113, 2796. (d) Severin, Th.; Adhikary, P.; Brautigam,
I. Chem. Ber. 1976, 109, 1179. (e) Iesce, M. R.; Cermola,
F.; Guitto, A.; Giordano, F.; Scarpati, R. J. Org. Chem. 1996,
61, 8677.
(18) Tishkov, A. A.; Lyapkalo, I. M.; Kozincev, A. V.; Ioffe, S.
L.; Strelenko, Yu. A.; Tartakovsky, V. A. Eur. J. Org. Chem.
2000, 3229.
(19) The formation of nitroso alkenes upon silylation of -
functionalized nitro compounds with BSA has been
unambiguously proved before (see Ref.5).
(20) For the preparation of silyl nitronates with Me3SiCl/Et3N
and BSA, see: Torssell, K.; Zeuthen, O. Acta. Chem. Scand.
1978, B32, 118.
(21) (a) Feger, H.; Simchen, G. Liebigs Ann. Chem. 1986, 1456.
(b) Feger, H.; Simchen, G. Liebigs Ann. Chem. 1986, 428.
(22) Hesse, M.; Meier, H.; Zeeh, B. Spectroskopische Methoden
in der Organischen Chemie; Georg Thieme Verlag:
Stuttgart, 1995, 108.
(23) Hesse, M.; Meier, H.; Zeeh, B. Spectroskopische Methoden
in der Organischen Chemie; Georg Thieme Verlag:
Stuttgart, 1995, 151.
(24) Makarenkova, L. M.; Bliznets, I. V.; Ioffe, S. L.; Strelenko,
Yu. A.; Tartakovsky, V. A. Russ. Chem. Bull. (Engl. Transl.)
2000, 49, 1261.
(25) See, for example, data for syn- and anti-isomers of
MeCH=NOH: Hesse, M.; Meier, H.; Zeeh, B.
Spectroskopische Methoden in der Organischen Chemie;
Georg Thieme Verlag: Stuttgart, 1995, 214.
(26) Afonin, A. V.; Ushakov, I. A.; Tarasova, O. A.; Shmidt, E.
Yu.; Michaleva, A. I.; Voronov, V. K. Russ. J. Org. Chem.
(Engl. Transl.) 2000, 36, 1777.
(27) See, for example, Perlmutter, P. Conjugate Addition
Reactions in Organic Synthesis; Pergamon: Oxford, 1992,
and references cited therein.
(28) Dilman, A. D. Ph.D. Thesis; N. D. Zelinsky Institute of
Organic Chemistry: Moscow, 2001.
(29) Gottlieb, H. E.; Kotlyar, V.; Nudelman, A. J. Org. Chem.
1997, 62, 7512.
(30) Bruson, H. A. U.S. Patent 2390918 (Resinous Products &
Chemical Co.), 1945; Chem. Abstr. 1946, 40, 2456.
(31) Bordwell, F. G.; Bartmess, J. E. J. Org. Chem. 1978, 43,
3101.
(32) Janowitz, A.; Vavrecka, M.; Hesse, M. Helv. Chim. Acta
1991, 74, 1352.
(33) Andruszkiewicz, R.; Silverman, R. B. Synthesis 1989, 953.
(34) Ono, N.; Kamimura, A.; Miyake, H.; Hamamoto, I.; Kaji, A.
J. Org. Chem. 1985, 50, 3692.
References
(1) Preliminary comunications: (a) Danilenko, V. M.; Ioffe, S.
L.; Strelenko, Yu. A.; Karpenko, N. F.; Kalinin, A. V.;
Tartakovsky, V. A. Bull. Acad. Sci. USSR Div. Chem. Sci.
(Engl. Transl.) 1987, 2453. (b) Tishkov, A. A.; Lyapkalo, I.
M.; Ioffe, S. L.; Strelenko, Yu. A.; Tartakovsky, V. A. Russ.
Chem. Bull. (Engl. Transl.) 1997, 205.
(2) Tishkov, A. A.; Kozintsev, A. V.; Lyapkalo, I. M.; Ioffe, S.
L.; Kachala, V. V.; Strelenko, Yu. A.; Tartakovsky, V. A.
Tetrahedron Lett. 1999, 40, 5075.
(3) Smirnov, V. O.; Tishkov, A. A.; Lyapkalo, I. M.; Ioffe, S.
L.; Strelenko, Yu. A.; Tartakovsky, V. A. Russ. Chem. Bull.
2001, 12, in press.
(4) (a) Dilman, A. D.; Tishkov, A. A.; Lyapkalo, I. M.; Ioffe, S.
L.; Strelenko, Yu. A.; Tartakovsky, V. A. Synthesis 1998,
181. (b) Dilman, A. D.; Tishkov, A. A.; Lyapkalo, I. M.;
Ioffe, S. L.; Kachala, V. V.; Strelenko, Yu. A.; Tartakovsky,
V. A. J. Chem. Soc., Perkin Trans. 1 2000, 2926.
(5) Ioffe, S. L.; Lyapkalo, I. M.; Tishkov, A. A.; Danilenko, V.
M.; Strelenko, Yu. A.; Tartakovsky, V. A. Tetrahedron
1997, 53, 13085.
(6) Danilenko, V. M.; Strelenko, Yu. A.; Karpenko, N. F.; Ioffe,
S. L.; Tartakovsky, V. A. Bull. Acad. Sci. USSR Div. Chem.
Sci. (Engl. Transl.) 1989, 1105.
(7) For a review of the preparative methods, see: von Schecken,
O.; Apel, G.; Schwarz, H. G.; Segnitz, A. In Methoden der
Organischen Chemie (Houben-Weyl), Part I; Georg Thieme
Verlag: Stuttgart, 1971, 181.
(8) (a) Yukawa, Y.; Sakai, M.; Suzuki, S. Bull. Chem. Soc. Jpn.
1966, 39, 2266. (b) Shinada, T.; Yoshihara, K. Tetrahedron
Lett. 1995, 36, 6701.
(9) (a) Carotti, A.; Campagna, F. Synthesis 1979, 56.
(b) Keumi, T.; Yamamoto, T.; Saga, H.; Kitajima, H. Bull.
Chem. Soc. Jpn. 1981, 54, 1579. (c) Fahey, J. L.; Firestone,
R. A.; Christensen, B. G. J. Med. Chem. 1976, 19, 562.
(d) Brubaker, A. N.; DeRuiter, J.; Whitmer, W. L. J. Med.
Chem. 1986, 29, 1094.
(10) (a) Ricardt, G. Bull. Soc. Chim. Fr. 1974, 3–4, 615.
(b) Ricardt, G.; Couturier, D. C. R. Acad. Sci., Ser. C 1977,
284, 191.
(11) (a) Van Bergen, T. J.; Kellogg, R. M. J. Org. Chem. 1971,
36, 1705. (b) Tsujimoto, N.; Mano, M.; Tamura, Y.
Japanese Patent 7304785, 1973; Chem. Abstr. 1973, 78,
147813.
(12) Wang, X.; Cheng, T.; Zhang, Y.; Jia, Q.; Mengshen, C.
Gaodeng Xuexiao Huahue Xuebao 1987, 8, 133; Chem.
Abstr. 1988, 108, 94444.
(13) Alcazar, J.; Almena, I.; Begtrup, M.; de la Hoz, A. J. Chem.
Soc., Perkin Trans. 1 1995, 2773.
(14) (a) Khalil, Z. H.; Abdel-Hafez, A. A.; Yanni, A. S.;
Moharam, A. M. Bull. Chem. Soc. Jpn. 1988, 61, 4143.
(b) Kerdesky, F. A. J.; Schmidt, S. P.; Holmes, J. H.; Dyer,
R. D.; Carter, G. W.; Brooks, D. W. J. Med. Chem. 1987, 30,
1177. (c) Unterhalt, B. Tetrahedron Lett. 1968, 1841.
(15) (a) Galinis, D. L.; McKee, T. C.; Pannell, L. K.; Cardellina,
J. H. II; Boyd, M. R. J. Org. Chem. 1997, 62, 8968.
(b) McKee, T. C.; Galinis, D. L.; Pannell, L. K.; Cardellina,
J. H. II.; Laakso, J.; Ireland, C. M.; Murray, L.; Capon, R. J.
J. Org. Chem. 1998, 63, 7805. (c) Kim, J. W.; Shin-ya, K.;
(35) Smirnova, A. A.; Perekalin, V. V.; Cherbakov, V. A. J. Org.
Chem. USSR (Engl. Transl.) 1968, 4, 2245.
(36) Zen, S.; Kaji, E. Bull. Chem. Soc. Jpn. 1970, 43, 2277.
(37) Kohler, E. P.; Engelbrecht, H. J. Am. Chem. Soc. 1919, 41,
764.
Synthesis 2002, No. 5, 635–647 ISSN 0039-7881 © Thieme Stuttgart · New York