Preparation and reactions of 3-phosphinyl-1-aza-1,3-butadienes. Synthesis of phosphorylated pyridine and pyrazole derivatives

Article abstract of DOI:10.1016/j.tet.2005.11.003

3-Phosphinyl 1-aza-1,3-butadienes 2 are obtained by aldol condensation between hydrazonoalkyl phosphine oxides and N,N-dimethylformamide dimethyl acetal. Transamination reaction of these azadienes with amines yields functionalized 1-aza-1,3-butadienes 3.

Full text of DOI:10.1016/j.tet.2005.11.003

Tetrahedron 62 (2006) 1095–1101
Preparation and reactions of 3-phosphinyl-1-aza-1,3-butadienes.
Synthesis of phosphorylated pyridine and pyrazole derivatives
a
a
a
Francisco Palacios,a, Domitila Aparicio, Yago Lopez, Jesus M. de los Santos
*
´
b
´
´
and Jose M. Ezpeleta
a
´ ´ ´
Departamento de Quımica Organica I, Facultad de Farmacia, Universidad del Paıs Vasco, Apartado 450, 01080 Vitoria, Spain
b
´
´
Departamento de Fısica Aplicada II, Facultad de Farmacia, Universidad del Paıs Vasco, Apartado 450, 01080 Vitoria, Spain
Received 20 September 2005; revised 2 November 2005; accepted 2 November 2005
Available online 21 November 2005
Abstract—3-Phosphinyl 1-aza-1,3-butadienes 2 are obtained by aldol condensation between hydrazonoalkyl phosphine oxides and
N,N-dimethylformamide dimethyl acetal. Transamination reaction of these azadienes with amines yields functionalized 1-aza-1,3-butadienes
3. Cycloaddition processes of these azadienes 2a with electron-poor dienophiles to give phosphorylated pyridine derivatives 9 and 15 are also
reported, while intramolecular cyclization reaction of heterodiene 2b affords phosphorylated pyrazole 17.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Hydrazones constitute an important class of compounds due
to the rich chemistry of the hydrazono group and have
attracted a great deal of attention in recent years because of
their range of applications.1 They have been extensively
used as versatile precursors in acyclic2 and heterocyclic
synthesis,3 and also form part of the structure of new
azapeptides,4 as well as biologically active compounds.5
Figure 1.
Aza-Diels–Alder (ADA) reactions6,7 of 1-azabutadienes are
However, as far as we know no examples of aza-
Diels–Alder (ADA) reaction of 1-azadienes containing
a phosphorus substituent at C-3 position (I, R1ZNMe2,
R3ZP(O)Ph2, Fig. 1), have been reported. Furthermore, it is
known that phosphorus substituents regulate important
biological functions,14 and that molecular modifications
involving the introduction of organophosphorus functiona-
lities in simple synthons could be very interesting for the
preparation of biologically active compounds.
gaining widespread acceptance as tools in heterocyclic
synthesis and have found use in the preparation of
compounds containing pyridine, quinoline, mono- and
diazaanthracene and other nitrogen rings. In particular,
a,b-unsaturated dimethylhydrazones have been widely used
in hetero Diels–Alder reactions, as 1-azadienes8 (I, R1Z
NMe2) (Fig. 1) with electron-deficient partners, as key steps
in a variety of syntheses of natural products and other
biologically relevant heterocycles.9
As a continuation of our work on the cycloaddition reaction
of 1-azadienes and on the chemistry of new phosphorus- and
nitrogen-substituted heterocycles, here we aim to explore
the behaviour of 1-azadienes derived from dimethylhydra-
zones, such as 3-phosphinyl-1-aza-1,3-butadiene Ia (I, R1Z
R4ZNMe2, R3ZP(O)Ph2) towards dienophiles (aZb), for
the preparation of phosphorus-substituted heterocycles IV
(Scheme 1), as well as the effect of subtituents at C-2
position of the azadiene. This strategy could open new
entries for the preparation of substituted six-membered
heterocycles.
In this context, we have been involved in the synthesis of
1-aza (I),10 2-aza-(II),11 and 1,2-diaza-1,3-butadienes
(III)12 (Fig. 1) as well as new strategies for the preparation
of nitrogen heterocyclic compounds.13
Keywords: Hydrazones; 1-Aza-1, 3-buladienes; Phosphorylated hetero-
cycles; Aza-Diels–Alder.
*
Corresponding author. Tel.: C34 945 013103; fax: C34 945 013049;
e-mail: francisco.palacios@ehu.es
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.11.003

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F. Palacios et al. / Tetrahedron 62 (2006) 1095–1101
gave the transamination product 3b in almost quantitative
yield (Scheme 3). The spectroscopic data are in agreement
with the assigned structure for compound 3b. This process
was extended to other functionalized amine derivatives.
Thus, 2-vinyloxy ethylamine reacted with 1-azadiene 2a
(RZH) and gave, after purification, N-functionalized
1-aza-1,3-butadiene 3a in 76% yield (Scheme 3).
Scheme 1.
2. Results and discussion
2.1. Preparation of 3-phosphinyl 1-aza-1,3-butadienes 2
1-Aza-1,3-butadienes 2 (RZH, Me), containing electron-
donating groups at N-1 and C-4 as well as an electron-
withdrawing group at C-3 position, were prepared by aldol
condensation between hydrazonoalkyl phosphine oxides 1
(RZH, Me) and N,N-dimethylformamide dimethyl acetal
(Scheme 2). Thus, reaction of b-hydrazono phosphine oxide
1a (RZH), prepared from methyl diphenylphosphine oxide,
DMF and N,N-dimethylhydrazine (see Section 3), with
N,N-dimethylformamide dimethyl acetal in refluxing toluene
(TLC control) led to the formation of 1-azadiene 2a (RZH) in
good yield (Scheme 2). In the same way, 2-methyl-substituted
1-azadiene 2b (RZMe) can be obtained by reaction of
hydrazonoalkyl phosphine oxide 1b (RZMe)10b with N,N-
dimethylformamide dimethyl acetal. These compounds 2
were characterized by their spectroscopic data, and the vicinal
coupling constant (3JPH) in the range of 15.0 Hz indicate a cis-
relationship between the phosphorus atom and the vinylic
proton, being consistent with an E-configuration for the
carbon–carbon double bond.15 31P NMR spectrum of 2a
showed one absorption atdP 33.1 ppm. Likewise, the 1H NMR
spectra of 2a gave a well resolved doublet for the vinylic
proton at dH 7.12 ppm (3JPHZ15.0 Hz), while in 13C NMR a
doublet appeared at dC 146.0 ppm (2JPCZ16.6 Hz) for the
methine carbon.
Scheme 3.
Next, we explore whether new phosphorylated 1-aza-1,
3-butadienes could be used as versatile tools for the
construction of nitrogen-containing heterocycles through
the cycloaddition reaction of these azadienes.
2.3. Cycloaddition reaction of 3-phosphinyl
1-aza-1,3-butadienes 2
The presence of electron-rich groups such as dimethylamino
substituents on the terminal nitrogen atom (N-1) and on the
terminal carbon atom (C-4) of the heterodiene system, may
favour the Aza-Diels–Alder (ADA) cycloaddition of these
substrates. In this way, 1-azadiene systems have been used as
building blocks for the preparation of a wide range of
heterocycles.16 However, aza-Diels–Alder (ADA) reaction of
1-aza-1,3-butadienes 2 containing phosphorus substituents
has not been reported, although, this strategy could be very
useful for the preparation of phosphorylated
azaheterocycles.17
Scheme 2.
As far as we know, this process represents the first example
for the preparation of 1-aza-1,3-butadienes containing a
phosphorus electron-withdrawing group (Scheme 2).
Initially, we studied the cycloaddition reaction of electron-
poor dienophiles such as tetracyanoethylene, naphthoqui-
none, diethyl azodicarboxylate, tosylisocyanate, diethyl
fumarate, diethyl maleate, or maleic anhydride to azadiene
2a. However, the formation of cyloadducts was not
observed and decomposition products were obtained. In
the same way, the addition of bromomaleic anhydride 4 or
ethyl propiolate 5 to 1-azadiene 2a gave the phosphorylated
a,b-unsaturated nitrile 6 in moderate to good yield
(Scheme 4). The formation of this nitrile 6 could be
explained by transfer of the dimethylamino group of the
azadienic system to the dienophile followed by oxidation to
nitrile 6 as reported before for other authors.18
These results prompted us to extend this reaction and to
explore whether other phosphorylated 1-aza-1,3-butadienes
can be obtained by transamination reaction of these
1-azadienes 2 with amine derivatives.
2.2. Transamination reaction of 4-dimethylamino
3-phosphinyl 1-aza-1,3-butadienes 2
We studied the transamination reaction between 1-azadienes
2 and simple and functionalized amines. Treatment of
1-azadiene 2b (RZMe) with pyrrolidine in refluxing EtOH

F. Palacios et al. / Tetrahedron 62 (2006) 1095–1101
1097
Scheme 4.
The addition of N-phenylmaleimide
7 to 1-aza-
1,3-butadiene 2a in the absence of solvent and at 100 8C
led to the formation of the functionalized bicyclic
cycloadduct 9 (yield of isolated compound 37%, Scheme 4).
All attempts to increase the yield of this cycloaddition by
addition of Lewis acids such as BF3, AlCl3, Cu(OTf)2, InCl3
or LiClO4 were unsuccessful giving to the decomposition of
the starting 1-azadiene 2a. As before, the structure of
compound 9 was assigned on the basis of NMR spectro-
scopic data, including MS data and its formation could be
rationalized through a initial [4C2] cycloaddition reaction
of 1-azadiene 2a with N-phenylmaleimide 7 as dienophile to
give tetrahydropyridine 8, which aromatization with the loss
of dimethylamine afforded substituted fused-pyridine 9
(Scheme 4).
Scheme 5.
A different behaviour was observed when 1-azadiene 2a
(RZH) was treated with an excess of diethyl acetylenedi-
carboxylate (DEAD) 10 in the absence of solvent and at
room temperature to give, in moderate yield the substituted
vinyl pyridine 15, instead of the expected phosphorylated
pyridine derivative 11 (Scheme 5).
This substituted vinyl pyridine 15 were characterized by its
NMR spectral data, where 1H NMR spectrum of 15 showed
a well resolved doublet at dH 7.89 ppm with coupling
constant 3JPHZ12.8 Hz corresponding to H-4. The structure
was finally determined by X-ray study of 1519 (Fig. 2). The
process could be explained through an initial [4C2]
cycloaddition reaction of 1-azadiene 2a with DEAD 10 to
give tetrahydropyridine 11, followed by elimination of
diethylamine and formation of dihydropyridine 12. Sub-
sequent addition of a second molecule of DEAD to this
dihydropyridine 12 may give a bicyclic heterocycle 13,
which five-membered ring opening and aromatization led to
the formation of pyridine 15.
Figure 2. ORTEP view of compound 15.
However, the formation of cyloadducts was not observed
and decomposition products were obtained. As reported by
Ghosez et al.,20 the presence of a methyl group at C-2 of the
1-azadiene system 2b shifts the dimethylamino group at N-1
out of the plane (steric inhibition of conjugation),
deactivating the diene system and hindering the cyclo-
addition reaction with dienophiles.
For this reason, we explored the behaviour of these
substrates 2b in the presence of LiClO4 as catalyst. Addition
of LiClO4 to methyl-substituted 1-azadiene 2b in the
presence or even in the absence of dienophile and using
nitromethane as solvent led to the formation of 4-phos-
phorylated pyrazole 17 (Scheme 6). Mass spectrometry
supported the molecular ion peak, while in the 31P NMR
Next, the reaction of 1-azabutadienes 2b substituted with a
methyl group at C-2 position as heterodienes with electron-
poor dienophiles such as diethyl acetylenedicarboxylate,
diethyl azodicarboxylate, or benzoquinone was explored.

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F. Palacios et al. / Tetrahedron 62 (2006) 1095–1101
distilled. All other reagents were recrystallized or distilled
as necessary. All reactions were performed under an
atmosphere of dry nitrogen. Analytical TLC’s were
performed with silica gel 60 F254 plates. Spot visualization
was accomplished by UV light or KMnO4 solution. Flash
chromatography was carried out using silica gel 60
(230–400 mesh). Melting points were determined with a
Electrothermal IA9100 digital apparatus and are uncor-
rected. 1H (300 MHz), 13C (75 MHz) and 31P NMR
(120 MHz) spectra were recorded on a Varian Unity Plus
300 MHz spectrometer, using tetramethylsilane (TMS)
1
(0.00 ppm) or chloroform (7.24 ppm) for H NMR spectra,
chloroform (77.0 ppm) for 13C NMR spectra, and phos-
phoric acid (85%) (0.00 ppm) for 31P NMR spectra.
Chemical shifts (d) are given in ppm; multiplicities are
indicated by s (singlet), br s (broad singlet), d (doublet), dd
(double-doublet), t (triplet), q (quadruplet) or m (multiplet).
Coupling constants (J) are reported in Hertz. Low-
resolution mass spectra (MS) were obtained on a Hewlett
Packard 5971 MSD Series spectrometer at 50–70 eV by
electron impact (EI) or on a Hewlett Packard 1100 MSD
Series spectrometer by chemical ionization (CI). Data are
reported in the form m/z (intensity relative to base peakZ
100). Infrared spectra (IR) were taken on a Nicolet FTIR
Magna 550 spectrometer, and were obtained as solids in
Scheme 6.
spectrum the phosphinyl group resonated at dP 19.2 ppm.
The 1H NMR spectrum showed an absorption at dH
7.07 ppm as a singlet for H-5 and 13C NMR spectrum
showed an absorption at dC 137.1 ppm as a doublet with
2
coupling constant JPCZ20.6 Hz for C-5 and at dC
1
110.4 ppm as a doublet with coupling constant JPC
Z
125.9 Hz for the carbon atom directly bonded to the
phosphorus atom (C-4). The formation of this pyrazole 17
could be explained by intramolecular cyclization involving
nucleophilic atack of the dimethylamino group at N-1 to the
carbon–carbon double bond to give pyrazolidine 16.
Subsequent loss of trimethylamine afforded 4-phosphory-
lated pyrazole 17 (Scheme 6).
KBr or as neat oils in NaCl. Peaks are reported in cmK1
.
Elemental analyses were performed in a Leco CHNS-932
instrument. Hydrazonoalkyl phosphine oxide 1b was
synthesized according to literature procedures.10b
Finally, the behaviour of functionalized 1-aza-1,3-butadiene
3a (Scheme 3) as heterodiene in intramolecular aza-
Diels–Alder (IADA) reaction was explored. However, the
formation of cycloadducts 18 was not observed in this
reaction and the starting compound 3a was recovered
unchanged. Neither standing the 1-azadiene in refluxing
xylene nor the use of Lewis acids as catalyst led to the
formation of cycloadducts, probably due to the
unfavourable configuration of the amino group in position 4.
3.1.1. Synthesis of 1-(dimethylhydrazono)ethenyl diphenyl-
phosphine oxide (1a). To a K60 8C stirred solution of
methyl diphenylphosphine oxide (10 mmol, 2.16 g) in THF
(40 mL), a solution of butyllithium (1.6 M in hexanes,
11 mmol, 6.9 mL) in THF (2 mL) was added under a
nitrogen atmosphere. After 30 min at the same temperature
a solution of DMF (15 mmol, 1.16 mL) in THF (5 mL) was
added dropwise and the reaction was kept to reach room
temperature for 16 h. After this time, H2O (10 mL) was
added to the reaction mixture and stirred for 45 min. HCl
(20%) was then added to the reaction mixture until pHZ1
and the mixture was stirred for 30 additional min. Then, the
aqueous phase was extracted with CH2Cl2 (3!15 mL) and
the organic phases were dried over anhydrous MgSO4 and
evaporated under vacuum. The obtained aldehyde, without
further purifications, was dissolved in dry chloroform
(40 mL) and N,N-dimethylhydrazine (11 mmol, 0.85 mL)
was then added at room temperature and stirred for 16 h.
The reaction mixture was washed with water (2!10 mL)
and the organic phase was dried over anhydrous MgSO4 and
evaporated under vacuum. Precipitation of the crude
product from ethyl ether and recrystallization from a
mixture of hexanes–CH2Cl2 (3/1) gave 1a (2.40 g, 84%
In conclusion, the synthesis of 1-dimethylamino-1-aza-
1,3-butadienes containing a phosphine oxide group at C-3 2
is described. The process implies aldol condensation
between hydrazonoalkyl phosphine oxides and
N,N-dimethylformamide dimethyl acetal. Electron-deficient
dienophiles such as N-phenylmaleimide or diethyl acet-
ylenedicarboxylate react with C-2 unsubstituted 1-aza-
dienes 2a to afford phosphorylated pyridine derivatives 9
and 15. However, 1-azadienes 2b substituted with a methyl
group at C-2 of the azadiene system do not react with
electron-poor dienophiles, and its cyclization in the
presence of LiClO4 to give phosphorylated pyrazole 17
has been described. Through these strategies reported in this
paper, new access to polysubstituted nitrogen- and
phosphorus-containing heterocycles can be designed.
1
two steps) as a white solid: 90–92 8C; H NMR (CDCl3)
Z
d 7.79–7.42 (m, 10H), 6.58–6.53 (m, 1H), 3.37 (dd, 2JPH
3
14.2 Hz, JHHZ5.9 Hz, 2H), 2.66 (s, 6H); 13C NMR
(CDCl3) d 133.1, 131.8, 131.7, 131.6, 131.5, 131.1, 131.0,
3. Experimental
3.1. General
2
130.9, 128.6, 128.5, 128.3, 125.9 (d, JPCZ7.5 Hz), 42.8,
1
35.7 (d, JPCZ68.5 Hz); 31P NMR (CDCl3) d 29.9; IR
(KBr) 3065, 2959, 2853, 1434, 1182; MS (CI) m/z 287 (MC
1, 100). Anal. Calcd for C16H19N2OP: C, 67.12; H, 6.69; N,
9.78. Found C, 67.10; H, 6.72; N, 9.77.
Solvents for extraction and chromatography were of
technical grade. All solvents used in reactions were freshly

F. Palacios et al. / Tetrahedron 62 (2006) 1095–1101
1099
3.2. General procedure for the synthesis of phosphorylated
1-azadienes (2)
131.8, 131.7, 131.1, 131.0, 128.2, 128.1, 127.9, 89.6 (d,
1JPCZ126.9 Hz), 87.0, 67.3, 47.4, 43.6; 31P NMR (CDCl3)
d 31.8; IR (NaCl) 3376, 2965, 1619, 1440, 1188; MS (EI)
m/z 383 (MC, 35). Anal. Calcd for C21H26N3O2P: C, 65.78;
H, 6.83; N, 10.96. Found C, 65.96; H, 6.85; N, 10.93.
To a stirred solution of b-hydrazono phosphine oxide 1a or
1b (1 mmol) in toluene (1 mL), was added N,N-dimethyl-
formamide dimethyl acetal (1.2 mmol, 0.16 mL) under a
nitrogen atmosphere, and the mixture was refluxed for 36 h.
Then, the solvent was evaporated under vacuum and the
crude product was purified by flash-chromatography (silica
gel, AcOEt/MeOH 85:15).
3.3.2. [3-(Dimethylhydrazono)-2-(diphenylphosphinoyl)-
but-1-enyl]pyrrolidine (3b). The title compound (0.36 g,
94%) obtained as a yellow oil from 1-azadiene 2b (1 mmol,
0.36 g) and pyrrolidine (2 mmol, 0.17 mL) after refluxing
for 24 h as described in the general procedure: RfZ0.84,
AcOEt/MeOH 3:1; 1H NMR (CDCl3) d 7.86–7.21 (m, 10H),
3.2.1. [3-(Dimethylhydrazono)-2-(diphenylphosphinoyl)-
propenyl]dimethylamine (2a). The title compound (0.24 g,
69%) obtained as a white solid from 2-(N,N-dimethyl-
hydrazono)ethyldiphenylphosphine oxide (1 mmol, 0.29 g)
3
6.57 (d, JPHZ15.0 Hz, 1H), 3.16–3.14 (m, 4H), 2.27 (s,
6H), 1.89 (s, 3H), 1.76–1.71 (m, 4H); 13C NMR (CDCl3)
d 164.2 (d, 2JPCZ9.6 Hz), 146.9 (d, 2JPCZ19.6 Hz), 134.0,
132.6, 132.1, 132.0, 131.9, 131.8, 131.0, 130.9, 130.6,
130.5, 130.1, 130.0, 127.5, 127.4, 127.3, 127.2, 97.6 (d,
1JPCZ115.3 Hz), 51.4, 46.4, 24.8, 21.1; 31P NMR (CDCl3)
d 29.7; IR (NaCl) 2945, 2859, 1606, 1175; MS (CI) m/z 382
(MCC1, 100). Anal. Calcd for C22H28N3OP: C, 69.27; H,
7.40; N, 11.02. Found C, 69.03; H, 7.41; N, 10.98.
1
as described in the general procedure: mp 92–93 8C; H
Z
3
NMR (CDCl3) d 7.83–7.27 (m, 11H), 7.12 (d, JPH
15.0 Hz, 1H), 3.07 (s, 6H), 2.47 (s, 6H); 13C NMR (CDCl3)
2
2
d 146.0 (d, JPCZ16.6 Hz), 131.1, 129.7, 129.2 (d, JPC
Z
8.1 Hz), 127.8, 127.7, 127.3, 127.2, 126.1, 126.0, 124.0,
1
123.9, 123.8, 123.2, 123.0, 87.4 (d, JPCZ115.3 Hz), 39.5,
38.7; 31P NMR (CDCl3) d 33.1; IR (KBr) 3436, 2906, 2793,
1600, 1527, 1122; MS (CI) m/z 342 (MCC1, 100). Anal.
Calcd for C19H24N3OP: C, 66.85; H, 7.09; N, 12.31. Found
C, 66.63; H, 7.08; N, 12.34.
3.3.3. Synthesis of 3-dimethylamino-2-(diphenylphos-
phinoyl)acrylonitrile (6). A mixture of 1-azadiene 2a
(1 mmol, 0.34 g) in xylene (3 mL) and the corresponding
dienophile (2 mmol) was stirred at room temperature under
a nitrogen atmosphere for 36 h. The solvent was evaporated
under vacuum and the crude product was purified by flash-
chromatography (silica gel, AcOEt/MeOH 95:5) to afford
compound 6 (76–83%) as a yellow oil: RfZ0.65, AcOEt/
3.2.2. [3-(Dimethylhydrazono)-2-(diphenylphosphinoyl)
but-1-enyl]dimethylamine (2b). The title compound
(0.25 g, 70%) obtained as a white solid from 2-(N,
N-dimethylhydrazono)propyldiphenylphosphine oxide
(1 mmol, 0.30 g) as described in the general procedure:
mp 78–80 8C; 1H NMR (CDCl3) d 7.85–7.29 (m, 10H), 6.55
MeOH 3:1; 1H NMR (CDCl3) d 7.76–7.33 (m, 11H), 3.31 (s,
2
3H), 3.11 (s, 3H); 13C NMR (CDCl3) d 157.0 (d, JPC
Z
12.6 Hz), 133.0, 131.8, 131.7, 131.6, 131.4, 131.2, 128.3,
3
(d, JPHZ15.4 Hz, 1H), 2.80 (s, 6H), 2.21 (s, 6H), 1.83 (s,
3H); 13C NMR (CDCl3) d 163.0, 150.3 (d, 2JPCZ18.6 Hz),
133.8, 132.4, 131.6, 131.4, 130.8, 130.6, 130.4, 130.3,
128.1, 119.0 (d, JPCZ12.6 Hz), 62.0 (d, JPCZ122.5 Hz),
46.9, 38.0; 31P NMR (CDCl3) d 28.1; IR (NaCl) 3423, 2925,
2182, 1613, 1434, 1367; MS (EI) m/z 295 (MCK1, 100).
Anal. Calcd for C17H17N2OP: C, 68.91; H, 5.78; N, 9.45.
Found C, 68.78; H, 5.77; N, 9.47.
2
1
1
130.2, 130.1, 127.0, 126.9, 95.6 (d, JPCZ115.3 Hz), 45.7,
42.1, 20.8; 31P NMR (CDCl3) d 30.7; IR (KBr) 3409, 2952,
2653, 1613, 1440, 1241; MS (CI) m/z 356 (MCC1, 100).
Anal. Calcd for C20H26N3OP: C, 67.59; H, 7.37; N, 11.82.
Found C, 67.75; H, 7.39; N, 11.83.
3.4. General procedure for the cycloaddition reaction.
Synthesis of phosphorylated pyridine derivatives (9) and
(15)
3.3. General procedure for the transamination reaction.
Synthesis of phosphorylated 1-azadienes (3)
A mixture of 1-azadiene 2a (1 mmol, 0.34 g) and the
corresponding dienophile (5–6 mmol) was stirred, without
solvent, at room temperature or 100 8C under a nitrogen
atmosphere. The reaction mixture was stirred for 3–5 h and
the crude product was purified by flash-chromatography
(silica gel).
To a stirred solution of 1-azadiene 2a or 2b (1 mmol) in dry
ethanol (4 mL), the corresponding amine (1.5–2 mmol) was
added under a nitrogen atmosphere. The reaction mixture
was stirred and refluxing for 8–24 h. The solvent was
evaporated under vacuum, and the crude product was
purified by flash-chromatography (silica gel, AcOEt/MeOH
95:5).
3.4.1. 3-(Diphenylphosphinoyl)-6-phenyl pyrrolo[3,4,-b]-
pyridine-5,7-dione (9). The title compound (0.16 g, 37%)
obtained as a white solid from 1-azadiene 2a and
N-phenylmaleimide (6 mmol, 1.1 g) after 5 h at 100 8C as
described in the general procedure. The crude product was
purified by flash-chromatography (silica gel, AcOEt/
3.3.1. [3-(Dimethylhydrazono)-2-(diphenylphosphinoyl)-
propenyl](2-vinyloxyethyl)amine (3a). The title com-
pound (0.29 g, 76%) obtained as a yellow oil from
1-azadiene 2a (1 mmol, 0.34 g) and 2-vinyloxy ethylamine
(1.5 mmol, 0.17 g) after refluxing for 8 h as described in the
1
hexanes 1:1): mp 193–195 8C; H NMR (CDCl3) d 9.18
1
3
3
general procedure: RfZ0.82, AcOEt/MeOH 3:1; H NMR
(CDCl3) d 9.39 (br s, 1H), 7.67–6.78 (m, 12H), 6.37 (dd,
(d, JPHZ6.1 Hz, 1H), 8.34 (d, JPHZ10.5 Hz, 1H),
7.59–7.27 (m, 15H); 13C NMR (CDCl3) d 176.3, 158.7 (d,
2JPCZ12.1 Hz), 135.9, 135.3, 135.2, 134.7, 133.1, 132.0,
131.9, 131.0, 130.8, 129.6, 129.3, 129.2, 129.1, 128.8,
126.4; 31P NMR (CDCl3) d 25.7; IR (KBr) 3320, 2975,
1689, 1420, 1267; MS (CI) m/z 425 (MCC1, 100). Anal.
3
3JHHZ6.1 and 14.0 Hz, 1H), 4.10 (d, JHHZ14.0 Hz, 1H),
3
3.96 (d, JHHZ6.1 Hz, 1H), 3.70–3.67 (m, 2H), 3.38–3.36
(m, 2H), 2.58 (s, 6H); 13C NMR (CDCl3) d 151.0, 149.5 (d,
2
2JPCZ17.6 Hz), 137.8 (d, JPCZ19.5 Hz), 134.5, 133.1,

1100
F. Palacios et al. / Tetrahedron 62 (2006) 1095–1101
´
los Santos thanks the Ministerio de Ciencia y Tecnologıa
(Madrid) for financial support through the Ramon y Cajal
Calcd for C25H17N2O3P: C, 70.75; H, 4.04; N, 6.60. Found
C, 70.66; H, 4.08; N, 6.64.
´
Program.
3.4.2. 6-(2-Dimethylamino-1,2-bis-methoxycarbonyl-
vinyl)-5-(diphenylphosphinoyl)pyridine-2,3-dicarboxylic
acid dimethyl ester (15). The title compound (0.37 g, 63%)
obtained as a white solid from 1-azadiene 2a and dimethyl
acetylenedicarboxylate (5 mmol, 0.62 mL) after 3 h at room
temperature as described in the general procedure. The
crude product was purified by flash-chromatography (silica
gel, AcOEt) and recrystallized from a mixture of CH2Cl2–
hexanes (1/5): mp 184–186 8C; 1H NMR (CDCl3) d 7.89 (d,
3JPHZ12.8 Hz, 1H), 7.61–7.33 (m, 10H), 3.85 (s, 3H), 3.71
(s, 3H), 3.66 (s, 3H), 2.97 (s, 3H), 2.50 (s, 6H); 13C NMR
(CDCl3) d 166.3, 165.7, 164.6, 163.3, 163.2, 155.0, 152.4,
142.5 (d, 2JPCZ12.6 Hz), 133.2, 132.1, 132.0, 131.9, 131.8,
130.8, 130.6, 129.2, 128.8, 128.6, 127.9, 127.8, 121.6,
121.5, 53.1, 52.9, 52.3, 50.6, 42.6; 31P NMR (CDCl3)
d 25.0; IR (KBr) 3356, 2925, 1739, 1440, 1195; MS (EI) m/z
580 (MC, 3). Anal. Calcd for C29H29N2O9P: C, 60.00; H,
5.04; N, 4.83. Found C, 59.77; H, 5.02; N, 4.82.
References and notes
1. For reviews see: (a) Elliot, E. C. In Comprehensive Organic
Functional Group Transformations II; Katritzky, A. R.,
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2. For recent contributions see: (a) Cook, G. R.; Kargbo, R.;
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X-ray analysis of compound 15. A yellow prismatic crystal of
C29H29N2O9P having approximate dimensions of 0.31!
0.22!0.16 mm3 was mounted on a glass fiber. All measure-
ments were carried out by means of a Nonius KappaCCD
diffractometer with graphite monochromated Mo Ka
radiation. Crystal data: C29H29N2O9P, TZ293 K, monoclinic,
3. For recent contributions see: (a) Ciesielski, M.; Pufky, D.;
´
Doering, M. Tetrahedron 2005, 61, 5942–5947. (b) Fernandez, I.;
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˚
˚
space group P21/n, with aZ8.9660(10) A, bZ28.402(3) A,
3
˚
˚
cZ12.031(9) A, bZ110.111(12)8, VZ2877(2) A and ZZ4
(dcalcdZ1.340 g cmK3), m(Mo Ka)Z0.152 mmK1
,
no
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absorption correction; 5072 unique reflections, 3828 with
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1H-pyrazole (17). To a stirred solution of 1-azadiene 2b
(1 mmol, 0.36 g) in nitromethane (3 mL), lithium perchlorate
was added until a 4 M solution of the salt was formed under a
nitrogen atmosphere. The reaction mixture was stirred at room
temperature for 16 h, washed with H2O (2!5 mL) and the
aqueous phase was extracted twice with CH2Cl2 (5 mL). The
organic layer was dried over MgSO4 and evaporated under
vacuum, and the crude product was purified by flash-
chromatography (silica gel, AcOEt) affording compound 17
(0.22 g, 74%) as a white solid: 176–178 8C; 1H NMR (CDCl3)
d 7.68–7.40 (m, 10H), 7.07 (s, 1H), 3.74 (s, 3H), 2.07 (s, 3H);
6. For reviews see: (a) Stocking, E. M.; Williams, R. M. Angew.
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2001, 57, 6099–6138. (e) Ghosez, L. Stereocontrolled Organic
Synthesis; Backwell: Oxford, 1994; pp 193–233.
13C NMR (CDCl3) d 152.2 (d, 2JPCZ9.5 Hz), 137.1 (d, 2JPC
Z
20.6 Hz), 134.1, 132.6, 131.8, 131.7, 131.6, 131.4, 128.6,
7. For recent contributions see: (a) Nicolau, K. C.; Safina, B. S.;
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Chem., Int. Ed. 2002, 41, 1941–1945.
1
128.4, 110.4 (d, JPCZ125.9 Hz), 38.7, 13.5; 31P NMR
(CDCl3) d 19.2; IR (KBr) 3104, 3051, 1527, 1440, 1195; MS
(EI) m/z 295 (MCK1, 100). Anal. Calcd for C17H17N2OP: C,
68.91; H, 5.78; N, 9.45. Found C, 69.10; H, 5.76; N, 9.43.
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Acknowledgements
´
The present work has been supported by the Direccion
General de Investigacion del Ministerio de Ciencia y
´
´
Tecnologıa (MCYT, Madrid DGI, BQU2000-0217) and
by the Universidad del Paıs Vasco (UPV, GC/2002). J.M. de
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19. CCDC-283335 contains the supplementary crystallographic
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www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
Cambridge Crystallographic Data Centre, 12 Union Road,
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