Stereochemical aspect of the intramolecular diaza-wittig reaction

Full text of DOI:10.1134/S1070428008120221

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 12, pp. 1840–1843. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © M.B. Supurgibekov, L. Hennig, B. Schulze, V.A. Nikolaev, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 12,
pp. 1866–1869.
SHORT
COMMUNICATIONS
Stereochemical Aspect of the Intramolecular
Diaza-Wittig Reaction
M. B. Supurgibekova, L. Hennigb, B. Schulzeb, and V. A. Nikolaeva
a St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: vnikola@VN6646.spb.edu
b Institut für organische Chemie, Universität Leipzig, Johannisallee 29, Leipzig, 04103 Germany
e-mail: bschulze@organik.chemie.uni-leipzig.de
Received June 25, 2008
DOI: 10.1134/S1070428008120221
Reactions of fluoroalkyl-substituted vinyl diazo
carbonyl compounds with triphenylphosphine are ac-
companied by spontaneous intramolecular cyclization
of the initially formed phosphazene, and pyridazines
are formed as a result of tandem process [1–3]. How-
ever, no analogous transformations occur with fluor-
ine-free vinyl diazo carbonyl compounds. Taking into
account that fluoroalkyl-containing vinyl diazo carbon-
yl compounds are usually characterized by cis con-
figuration* of the double bond [1, 4] and that their
fluorine-free analogs are trans isomers [5, 6], the most
probable reason for their different reactivities is dif-
ferent arrangement of functional groups (CO2Alk,
CN2) at the double C=C bond. The goal of the present
work was to compare chemical transformations of
diastereoisomeric fluoroalkyl-containing and fluorine-
free phosphazenes derived from vinyl diazo carbonyl
compounds.
diffraction data. It is known that configuration of the
double C=C bond does not change in the Staudinger
reaction of vinyl diazo carbonyl compounds with
phosphines.
The reaction of the pure cis isomer of vinyl diazo
ketone Ia with triphenylphosphine gave 4-trifluoro-
methyl-substituted pyridazine VI in more than 70%
yield, while intermediate cis-phosphazene IIIa could
not be isolated from the reaction mixture, in keeping
with our previous data [3]. In analogous reaction with
a mixture of cis and trans isomers Ia and Ib at a ratio
of ~1:1 we isolated 43% of pyridazine VI together
with pure trans-phosphazene IIIb (39%) (Scheme 1).
The structure and relative configuration of the latter
was determined by spectral data and X-ray analysis.
More nucleophilic tris(dimethylamino)phosphine
reacted with a mixture of cis- and trans-isomeric vinyl
diazo ketones Ia and Ib (~1 :1) to give a mixture of
cis- and trans-phosphazenes IVa and IVb in an overall
yield of 92%, their ratio being the same as for initial
diazo ketones Ia and Ib (~1 : 1, according to the
As substrates we selected phosphazenes IIIa, IIIb,
IVa, IVb, and V with cis and trans configuration of
the double C=C bond, which were synthesized from
diazo ketones Ia and Ib and diazo ester II and tri-
phenylphosphine and tris(dimethylamino)phosphine.
O
O
The relative configuration of stereoisomeric vinyl
diazo ketones Ia and Ib was determined by NMR
spectroscopy using NOE, COLOC, and HMQC tech-
niques, and the configuration of diazo ester II was
assigned on the basis of the coupling constants for
protons at the double bond (2-H and 3-H) and X-ray
MeO
O
MeO
O
R1
R2
R1
R2
PX3
N2
N
N
Ia, Ib, II
IIIa, IIIb, IVa, IVb, V
I, R1 = CF3, R2 = Me, cis (a), trans (b); II, R1 = H, R2 = OMe,
trans; III, R1 = CF3, R2 = Me, X = Ph, cis (a), trans (b);
IV, R1 = CF3, R2 = Me, X = NMe2, cis (a), trans (b); V, R1 =
H, R2 = OMe, X = Ph, trans.
* Hereinafter, cis and trans arbitrarily denote mutual orientation of
the CO2Alk and C=N2 groups at the double C=C bond with no
account taken of group seniority.
1840

STEREOCHEMICAL ASPECT OF THE INTRAMOLECULAR DIAZA-WITTIG REACTION
1841
Scheme 1.
O
P(NMe2)3
MeO
F3C
N
N
(Me2N)3P
92%
50–60°C
–(Me2N)3P=O
O
O
Me
F3C
Me
OMe
IVa, IVb
cis–trans ~1:1
MeO
O
N
F3C
Me
N
O
N2
Ia, Ib
cis–trans ~1:1
O
N
PPh3
OMe
VI, 43%
IIIb (39%) or IVb (18%)
Ph3P
20°C
+
–Ph3P=O
F3C
O
Me
IIIa
1H NMR data). Phosphazenes IVa and IVb turned out
to be less reactive that their analogs IIIa and IIIb
derived from triphenylphosphine, and they did not
undergo subsequent diaza-Wittig reaction at room tem-
perature (18–20°C). On the other hand, heating of
a mixture of stereoisomeric phosphazenes IVa and IVb
in benzene at 65–68°C resulted in the formation of
45% of pyridazine VI, and 18% of unreacted trans
isomer IVb was recovered from the reaction mixture.
The structure of phosphazene IIIb, cis/trans-phos-
phazenes IVa/IVb, and pyridazine VI was determined
by 1H and 13C NMR spectroscopy.
trans-V in benzene for 20 h, we isolated 23% of pyrid-
azine VII and 76% of unreacted initial phosphazene V.
We can conclude that the reactivity of fluorinated
and fluorine-free vinyl diazo carbonyl compounds is
governed by configuration of the double C=C bond:
phosphazenes with cis orientation of functional groups
(CO2Alk, CN2) at the double C=C bond readily under-
go intramolecular diaza-Wittig reaction with formation
of the corresponding pyridazines, whereas trans
isomers do not react.
Methyl cis-4-diazo-5-oxo-3-trifluoromethylhex-2-
enoate (Ia) was synthesized by the Wittig reaction
from 3-diazo-1,1,1-trifluoropentane-2,4-dione and
methyl (triphenyl-λ5-phosphanylidene)acetate. Yield
75%, bp 30–33°C (0.5 mm), Rf 0.6 (petroleum ether–
The above experimental data suggest that initially
formed cis-phosphazenes IIIa and IVa undergo spon-
taneous intramolecular diaza-Wittig reaction, and the
two-step process finally yields pyridazine VI. Phos-
phazines IIIb and IVb having trans-configured double
C=C bond do not undergo diaza-Wittig reaction and
remain unchanged. This assumption was confirmed by
photochemical isomerization of trans-phosphazene V
to the corresponding cis isomer and subsequent cy-
clization of the latter to pyridazine VII (Scheme 2).
After irradiation (quartz light filter, λ > 210 nm) of
1
diethyl ether, 1:1) [4]. H NMR spectrum (300 MHz,
CDCl3): 2.15 s (3H), 3.71 s (3H), 6.51 s (1H).
cis- and trans-Isomeric vinyl diazo ketones Ia and
Ib and trans-diazo ester II were synthesized by the
diazo transfer reaction [7, 8] from the corresponding
vinyl carbonyl compounds using p-acetylaminoben-
zenesulfonyl azide (p-ABSA) and DBU [9] in diethyl
ether. In the synthesis of Ia and Ib, the starting mate-
Scheme 2.
O
COOMe
OMe
P(NMe2)3
P(NMe2)3
MeO
N
N
N
hν
MeO
N
N
–(Me2N)3P=O
N
O
O
OMe
O
OMe
trans-V
cis-V
VII, 23%
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 12 2008

SUPURGIBEKOV et al.
1842
rial was a ~1:1 mixture of cis- and trans-vinyl ketones
prepared by reaction of 1,1,1-trifluoropentane-2,4-di-
one with methyl (triphenyl-λ5-phosphanylidene)ace-
tate. Compound II was synthesized from commercial
glutaconic acid dimethyl ester (Aldrich).
1H NMR spectrum, δ, ppm: 2.83 s (3H, CH3), 4.30 s
(3H, OCH3), 7.34 s (1H, CH). 13C NMR spectrum, δC,
ppm: 27.96, 56.19, 116.2 q (3JCF = 6.0 Hz), 121.3 q
(1JCF 274.0 Hz), 131.2 q (2JCF = 37 Hz), 150.1, 166.0,
196.4.
Methyl cis- and trans-4-diazo-5-oxo-3-trifluoro-
methylhex-2-enoates Ia and Ib were synthesized
from 2 g (9.5 mmol) of a mixture of the corresponding
vinyl ketones, 3.4 g (14.2 mmol) of p-ABSA, and
0.36 g (2.3 mmol) of DBU. Yield 0.96 g (43%), a mix-
ture of cis and trans isomers at a ratio of 1:1, yellow
liquid, bp 45–50°C (1–2 mm), Rf 0.34 (petroleum
Methyl trans-5-oxo-3-trifluoromethyl-4-(tri-
phenyl-λ5-phosphanylidenehydrazono)hex-2-enoate
(IIIb). Yield 210 mg (39%), yellow crystals, mp 140–
140.5°C (decomp., from Et2O), Rf 0.13 (ethyl acetate).
1H NMR spectrum, δ, ppm: 2.22 s (3H, CH3), 3.79 s
(3H, OCH3), 6.12 s (1H, CH), 7.45–7.72 m (15H,
H
arom). Found, %: C 62.33; H 4.50; N 5.55.
1
ether–ethyl acetate, 2:1). H NMR spectrum, δ, ppm:
C26H22F3N2O3P. Calculated, %: C 62.6; H 4.5; N 5.6.
Dimethyl trans-4-(triphenyl-λ5-phosphanylidene-
hydrazono)pent-2-enedioate (V). Triphenylphos-
phine, 1 mmol, was dissolved in a minimal amount of
diethyl ether (~3 ml), 1 mmol of diazo ester II was
added, and the mixture was left to stand for 4 h at
room temperature in the dark with protection from
atmospheric air. The precipitate was filtered off,
washed with cold benzene (2×1 ml), and dried under
reduced pressure (1–2 mm) at 18–20°C. Yield 423 mg
(87%), yellow crystals (from diethyl ether), mp 108–
109°C, Rf 0.16 (petroleum ether–ethyl acetate, 3:1).
1H NMR spectrum, δ, ppm: 3.76 s and 3.78 s (3H each,
OCH3), 7.42–7.74 m (16H, C6H5, 2-H), 8.12 d (1H,
cis isomer Ia: 2.25 s (3H, CH3), 3.81 s (3H, OCH3),
6.60 s (1H, CH); trans isomer Ib: 2.34 s (3H, CH3),
3.82 s (3H, OCH3), 7.01 s (1H, CH). 13C NMR spec-
trum, δC, ppm: cis isomer Ia: 25.7, 52.6, 65.4, 122.7 q
(1JCF = 275.8 Hz), 126.8 q (3JCF = 4.6 Hz), 128.0 q
(2JCF = 34.5 Hz), 163.6, 188.1; trans isomer Ib: 26.7,
60.7, 66.2, 121.6 q (1JCF = 275.8 Hz), 127.4 q (3JCF
=
4.6 Hz), 127.6 q (2JCF = 34.5 Hz), 164.8, 188.9. Mass
spectrum, m/z (Irel, %): 208 [M – 28]+ (87), 193 (100),
183 (12), 180 (25), 165 (47), 151 (30), 137 (40), 123
(20), 107 (52), 75 (30).
Dimethyl trans-4-diazopent-2-enedioate (II) was
synthesized from 0.1 g (0.63 mmol) of dimethyl gluta-
conate, 0.19 g (0.7 mmol) of p-ABSA, and 0.152 g
(0.7 mmol) of DBU [5]. Yield 0.095 g (85%), yellow
crystals (from Et2O), mp 72–73°C, Rf 0.43 (petroleum
3-H, 3J = 16.0 Hz). 13C NMR spectrum, δC, ppm: 51.82
1
and 51.90 (OCH3), 119.91 (C2), 127.05 d (Ci, JCP
=
93.8 Hz), 129.29 d (Cm, JCP = 10.9 Hz), 130.07 (C3),
3
1
2
ether–ethyl acetate, 3:1). H NMR spectrum, δ, ppm:
133.23 (Cp), 134.07 d (Co, JCP = 8.9 Hz), 141.01 d
3.75 s (3H, OCH3), 3.85 s (3H, OCH3), 5.73 d (1H,
(C=N, 3JCP = 41.9 Hz), 166.68 and 170.40 (C=O). UV
spectrum (ethanol), λ, nm (logε): 219 (3.53), 359
(3.33). Found, %: C 67.29; H 5.14; N 6.47.
C25H23N2O4P. Calculated, %: C 67.3; H 5.2; N 6.3.
3-H, 3J = 16.2 Hz), 7.33 d (1H, 2-H, 3J = 16.2 Hz).
Reaction of diazo ketones Ia and Ib with tri-
phenylphosphine. A mixture of cis and trans isomers
Ia and Ib (~1:1), 250 mg (1 mmol), was added to
a solution of 278 mg (1 mmol) of triphenylphosphine
in ~3 ml of diethyl ether, and the mixture was kept for
2 h at room temperature in the dark with protection
from atmospheric air. The precipitate was filtered off,
washed with cold diethyl ether (2×1 ml), and dried
under reduced pressure to obtain 195 mg of trans-
phosphazene IIIb. The filtrate was evaporated, and the
residue was subjected to column chromatography on
silica gel (7 g) using petroleum ether–ethyl acetate as
eluent (10:1 to 3:1, gradient elution) to isolate (in the
order of elution) 95 mg of pyridazine VI and 15 mg of
trans-phosphazene IIIb.
Photolysis of phosphazene (V). A solution of
0.43 g (1.24 mmol) of trans-V in 20 ml of a mixture of
petroleum ether and diethyl ether (2:1) was irradiated
for 20 h at λ > 210 nm (quartz light filter). The
precipitate was filtered off, washed with petroleum
ether (2 ml), and dried in air. We thus isolated 10 mg
of pyridazine VII. The mother liquor was evaporated,
the residue was applied to 1 g of silica gel and trans-
ferred to a column charged with 10 g of silica gel, and
the column was eluted with petroleum ether–ethyl
acetate (3:1 to 1:1, gradient elution) to isolate (in the
order of elution) 35 mg of pyridazine VII and 330 mg
(76%) of unreacted phosphazene V.
1-(6-Methoxy-4-trifluoromethylpyridazin-3-yl)-
ethanone (VI). Yield 95 mg (43%), colorless liquid,
Rf 0.35 (petroleum ether–ethyl acetate, 2:1) [3].
Methyl 6-methoxypyridazine-3-carboxylate
(VII). Yield 45 mg (23%), colorless crystals (from
diethyl ether), mp 119–120°C, Rf- = 0.6 (ethyl acetate).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 12 2008

STEREOCHEMICAL ASPECT OF THE INTRAMOLECULAR DIAZA-WITTIG REACTION
1843
1H NMR spectrum, δ, ppm: 4.05 s (3H, OCH3), 4.24 s
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 12 2008