Synthesis and reactivity of imines derived from bisphosphonates and 3-phosphorylated 2-aza-1, 3-dienes

Article abstract of DOI:10.1016/S0040-4020(00)00570-6

The synthesis and some reactions of imines derived from aminoalkylbisphosphonates and 2-aza-1,3-butadienes is described. Bisphosphonylalkylimino compounds are useful intermediates in the preparation of aminoalkylbisphosphonate derivatives by reduction of the imino linkage with sodium triacetoxyborohydride as well as in the synthesis of 2-aza-1,3-butadienes by an olefination reaction. The electrocyclization of phosphorylated 2-aza-1,3,5-trienes afforded substituted 2-phosphorylated pyridines. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00570-6

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 6319±6330
Synthesis and Reactivity of Imines Derived from Bisphosphonates
and 3-Phosphorylated 2-Aza-1,3-dienes
*
Francisco Palacios, Marie J. Gil, Eduardo Martõnez de Marigorta and Marta Rodrõguez
Â
Â
  Â
Departamento de Quõmica Organica, Facultad de Farmacia, Universidad del Paõs Vasco, Apartado 450, 01080 Vitoria-Gasteiz, Spain
Received 3 April 2000; revised 24 May 2000; accepted 15 June 2000
AbstractÐThe synthesis and some reactions of imines derived from aminoalkylbisphosphonates and 2-aza-1,3-butadienes is described.
Bisphosphonylalkylimino compounds are useful intermediates in the preparation of aminoalkylbisphosphonate derivatives by reduction of
the imino linkage with sodium triacetoxyborohydride as well as in the synthesis of 2-aza-1,3-butadienes by an ole®nation reaction. The
electrocyclization of phosphorylated 2-aza-1,3,5-trienes afforded substituted 2-phosphorylated pyridines. q 2000 Elsevier Science Ltd. All
rights reserved.
Aminophosphonic acids, which are analogues of amino
acids, and their phosphapeptide derivatives are both
mimetics of amino acids and peptides, with interesting
biological properties.1,2 For instance, a-amino phospho-
nates have been used as haptens for the preparation of cata-
lytic monoclonal antibodies3a and as enzymatic inhibitors
with therapeutic use,3b while b-aminophosphonates have
been found to be potent and selective inhibitors of farnesyl
protein transferase (FPT) and therefore they may prove
useful as antitumor agents.3c Furthermore, some amino-
alkylbisphosphonic acid derivatives have been used as
spin traps4 and have recently gained importance in medi-
cinal chemistry as antiin¯ammatory agents and for the treat-
ment of bone diseases related to calcium metabolism.5
These include acyclic compounds such as pamidronate 1a
(nˆ1) or alendronate 2b (nˆ2) or cyclic derivatives such as
pyridyl- (NE-97220) 2a or cycloheptyl-aminomethyl-
bisphosphonic acids (cimadronate, YM-175) 2b, which
show increasing antiresorptive activity compared to
previous bisphosphonate derivatives which lack N-contain-
ing functionalities such as clodronate or etidronate (Fig. 1).6
the preparation of new aminophosphonic derivatives such as
iminoalkylphosphonates 3 and phosphorylated 2-aza-1,3-
butadienes 4 (Fig. 2). 2-Azadienes represent an important
class of compounds and have become useful key inter-
mediates in organic synthesis for the construction of both
heterocyclic systems and open chain polyfunctionalized
compounds.7 These heterodienes 4, analogues of 2-aza-
dienes derived from a-amino acids8 5, where the carboxy-
late group has been isosterically replaced by a phosphonate,
may be useful intermediates for the synthesis of more
complex cyclic and acyclic a-aminophosphonate deriva-
tives with potentially increased biological activity.
We envisaged obtaining compounds of type 3 and 4 accord-
ing to the following retrosynthetic scheme where, after
condensation of aminomethyldiphosphonate 6 with a
carbonyl compound, the resulting imine 3 could be ole®-
nated by means of a Wadsworth±Emmons reaction with the
appropriate aldehyde to give rise to 3-phosphorylated 2-aza-
1,3-butadiene 4. This would be a highly versatile route
starting from very simple precursors, which would allow
the introduction of a great variety of functional groups in
positions 1 and 4 of the azadiene (Scheme 1).
Taking this into account, we decided to devise a route for
Figure 1.
Keywords: aminobisphosphonates; 2-aza-1,3-dienes; 2-aza-1,3,5-trienes; 2-phosphoryl pyridines.
* Corresponding author. Tel.: 134-945-013103; fax: 134-945-130756; e-mail: qoppagaf@vf.ehu.es
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00570-6

6320
F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
Scheme 2.
Figure 2.
phosphonates with structures similar to compounds 2 (Fig.
1), and, therefore, with potential biological activity on the
metabolism of calcium in bones. Although several different
nucleophiles including methyl lithium, acetylacetone
enolate, piperidine, triethylamine or sodium borohydride
were used, no reaction was detected in any case. Therefore,
we performed the reduction of some of the imines in the
presence of acetic acid with NaHB(OAc)3 prepared in situ,10
and obtained the expected aminoalkylphosphonates 8 with
acceptable yields (see Scheme 3 and Table 2). The structure
of compounds 8 were con®rmed by means of spectroscopic
data. Thus, the 1H NMR spectrum of compound 8a shows a
triplet (2JHPˆ21.3 Hz) at dH 3.25 ppm assignable to the
methine proton, and the signal corresponding to the benzylic
protons at dH 3.93 ppm. The methine carbon resonates at dC
53.1 ppm as a triplet (1JCPˆ146.0 Hz), while the benzylic
one appears at 54.6 as a singlet. Formation of aminophos-
phonates 8 could be explained by initial protonation of the
imine moiety of compound 3 followed by nucleophilic addi-
tion of the hydride to the iminium salts 7 (see Scheme 3).
Scheme 1.
Imines 3 were easily obtained by simple condensation of
aminomethyldiphosphonate 69 and aromatic (Table 1,
entries 1±3), heteroaromatic (Table 1, entries 4±6), a,b-
unsaturated aldehydes (Table 1, entry 7) and ketones such
as cycloheptanone, norbornan-2-one (Table 1, entries 8 and
9) and diethyl ketomalonate (Table 1, entry 10) (Scheme 2).
Compounds 3 were characterized by their spectroscopic
data. Thus, in the 1H NMR spectrum of iminebisphos-
phonate 3b the methine proton resonates at dH 4.31 ppm
2
as a triplet with coupling constant JHPˆ18.3 Hz, and the
imine hydrogen appears at dH 8.25 ppm also as a triplet
(4JHPˆ4.2 Hz), while the 13C NMR shows a triplet
(1JCPˆ149.5 Hz) corresponding to the methine carbon at
Following our synthetic plan to make derivatives of
a-aminophosphonates (Scheme 1) we investigated a route
towards 2-aza-1,3-butadienes 4 based on the ole®nation
reaction of aldehydes and functionalized imines 3. In this
context, we have previously used b-functionalized imines or
3
dC 68.1 ppm and another triplet (dC 167.5, JCPˆ15.1 Hz)
for the imine carbon. The phosphonate group resonates at dP
16.0 ppm in the 31P NMR spectrum.
Taking into account the importance of aminoalkylbisphos-
phonate derivatives as antiin¯ammatory agents and for the
treatment of bone diseases related to calcium metabolism5,6
we decided to further explore the reactivity of imines 3 with
nucleophiles, in order to prepare funtionalized aminoalkyl-
Table 1. Imines 3 obtained
Entry Compound
R1
R2
Yield (%)a
1
2
3
3a
3b
3c
Ph
p-Me±C6H4
o-(CH2vCH±CH2O)C6H4
H
H
H
60
87
70
4
3d
H
H
92
Scheme 3.
Table 2. Aminoalkylbisphosphonates 8 obtained
5
6
3e
3f
70
65
Entry
1
Compound
R1
R2
H
Yield (%)
60
H
H
8a
p-Me±C6H4
7
8
3g
3h
(E)-Ph±CHvCH
±CH2±CH2±CH2±CH2±
CH2±CH2±
70
70
2
3
8b
8c
H
40
71
±CH2±CH2±CH2±
CH2±CH2±CH2±
9
3i
3j
60
40
10
CO2Et
CO2Et
4
8d
67
a Yield of products after ¯ash chromatography.

F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
6321
the 4 position, and while developing this work19 the syn-
thesis of azadienes substituted with a phosphonyl group20 in
the 4 position was reported elsewhere.
According to this synthetic design, the ole®nation reaction
of imines 3 was initially carried out using several different
bases including methyl and butyl lithium, potassium tert-
butoxide and the superbase t-butyl-tris(tetramethylene)-
phosphazene (BTPP), but taking into account the partially
stabilized nature of the carbanion we reasoned that a weaker
base such as cesium carbonate in THF/i-PrOH would
suf®ce.21 In fact, the use of this base provided good yields
of the 2-azadienes 4 (Scheme 4 and Table 3) when aliphatic,
aromatic or heteroaromatic aldehydes were used, in shorter
reaction times and with the advantage that the reaction could
be run at room temperature and worked-up in a very easy
way. These azadienes 4 were identi®ed by means of spectro-
Scheme 4.
1
enamines derived from phosphazenes, phosphonium salts,
phosphine oxides and phosphonates for the construction of
carbon±carbon double bonds in the synthesis of acyclic
derivatives such as oximes,11a,b allylamines,11c hydra-
zones,11d and b-amino functionalized compounds.11e Both
the synthesis and some reactions of electronically neutral
2-azadienes12 or electron-rich heterodienes13 have been
reported. However, electron-poor dienes have received
much less attention. In fact, azabutadienes of this type
were limited to 3- or 4-substituted electron-de®cient hetero-
dienes derived from a-14 or b-amino acids15 as well as to
4,4-16 and 3,4-electron-withdrawing substituted 2-aza-
dienes.15,17 Likewise, we reported the preparation of
azadienes substituted with a phosphine oxide group18 in
scopic data. The most characteristic signal in the H NMR
spectrum of compound 4ba is the doublet (dH 7.05 ppm,
2JHPˆ16.6 Hz) corresponding to the vinylic proton coupled
with the vicinal phosphorus nucleus. According to this
coupling constant22 and the NOE experiments carried out
on some of the azadienes, we conclude that only the E
isomer is formed in the ole®nation reaction of imines
derived from bisphosphonates, since no traces of the Z
compound are observed.
This methodology can also be applied to the synthesis of
3-azatriene 9 (Scheme 4) when the corresponding a,b-
unsaturated imine derived from (E)-cinnamaldehyde 3g
was used (Table 4, entry 1). Selective decoupling and
Table 3. 2-Aza-1,3-butadienes 4 obtained
Entry
1
Compound
R1
R3
Base
Yield (%)a
4aa
Ph
Me
MeLi
BuLi
t-BuOK
48
50
55
2
3
4ab
4ac
Ph
Ph
p-Me±C6H4
BTPP
t-BuOK
50
55
Ph
BTPP
45
65
50
47
67
Cs2CO3
BTPP
MeLi
4
5
4ad
4ba
Ph
p-Me-C6H4
CO2Et
p-Me±C6H4
Cs2CO3
6
7
4bb
4bc
p-Me±C6H4
p-Me±C6H4
H
BTPP
80a
Cs2CO3
50
8
4bd
p-Me±C6H4
Cs2CO3
50
9
4ca
4cb
4da
o-(CH2vCH±CH2O)C6H4
o-(CH2vCH±CH2O)C6H4
p-NO2±C6H4
Me
BuLi
Cs2CO3
BuLi
30
60
71
10
11
p-Me±C6H4
Cs2CO3
60
12
13
4ea
4fa
p-Me±C6H4
Cs2CO3
BuLi
55
70
Me
a Yield of product without puri®cation.

6322
F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
Table 4. Azatrienes 9 and 10 obtained
compound 4ca also failed, showing the remarkable inertness
of these azadienes in [412] cycloaddition reactions.
Entry
1
Comp.
R1
R3
Base
Yield (%)
Therefore, we explored the potential utility of azatrienes in
intramolecular electrocyclization reactions, since thermal
6p-electrocyclization processes have been already
described for azatrienes derived from a-amino acids.23
Heating 3-azatriene 9 did not produce the heterocyclic
compound, but in the case of 2-azatrienes 10 it did even-
tually provide 2-phosphonylpyridine derivatives 12 with
moderate yields (Scheme 5). We would like to note the
low value of the coupling constant between the phosphorus
and the vicinal proton in the pyridine ring (3JHPˆ6.5 Hz)
compared to the value found in the open chain precursor
(3JHPˆ14±18 Hz). This change is not detected in the 13C
NMR spectra, where the coupling constants remain similar
to those in the precursor azatrienes. Formation of pyridines
12 can be explained by thermal 6p-electrocyclization of
2-azatrienes 10 followed by aromatization of dihydropyri-
dines 11, as has been reported for azatrienes derived from
a-amino acids.23a These results are consistent with thermal
rearrangements of 2-azatrienes24 to obtain pyridine deriva-
tives, while electrocyclizations of 3-azatrienes were
performed with more dif®culty and required very high
temperatures.25
9
±
±
BTPP
Cs2CO3
59
64
2
3
10be
10bf
p-Me±C6H4
p-Me±C6H4
Ph
BTPP
Cs2CO3
40
60
CH3
BTPP
Cs2CO3
40
70
4
10eb
Ph
Cs2CO3
50
1
NOE experiments were carried out on H NMR in order to
assign the vinylic protons and to establish the stereo-
chemistry of this azatriene. For instance, when selective
saturation of the doublet at dH 8.4 ppm corresponding to
the imine proton in 3-azatriene 9 was performed, NOE
effect (32%) was observed for the vinylic proton close to
the phenyl group and also for the protons in the phosphonate
group (18%).
In a similar way, the preparation of 2-azatrienes 10 by ole®-
nation reaction of the imines 3 with crotonaldehyde or
cinnamaldehyde (Table 4, entries 2±4) can be performed.
The spectrum of 2-azatriene 10bf shows a multiplet for the
vinylic proton close to the methyl group at dH 6.06 ppm, a
In conclusion, we describe here a straightforward method
for the synthesis of imines 3 or amines 8 derived from
bisphosphonates as well as azadienes 4, azatrienes 9, 10
and pyridines 12 derived from aminophosphonates. Amino-
phosphonates show interesting biological properties1,3 while
aminoalkylphosphonate derivatives have generated great
interest in medicinal chemistry as anti-in¯ammatory agents
and for the treatment of bone diseases.5,6
3
double doublet at dH 6.74 ppm with JHPˆ18.9 Hz, and
3JHHˆ11.0 Hz, assignable to the proton vicinal to the phos-
phonate group and another double doublet at dH 6.75 ppm
(3JHHˆ23.4 and 3JHHˆ10.5 Hz) corresponding to the middle
vinylic proton.
Electron-poor 2-azadienes derived from amino acids have
been used in the synthesis of heterocyclic systems through
cycloaddition reactions8,14±17 and, therefore, we hoped that
azadienes 4 derived from aminophosphonates would react
with dienophiles in inverse demand hetero-Diels±Alder
reactions to provide substituted pyridine and related hetero-
cyclic systems. Nevertheless, azadienes 4 did not react with
electron-rich dienophiles such as cyclohexanone±pyrroli-
dine enamine, nor with electron-poor dienophiles including
tetracyanoethylene, dimethyl acetylenedicarboxylate and
4-phenyl-1,2,4-triazoline-3,5-dione. Even the LiClO4
promoted intramolecular cycloaddition12a,15b reaction on
Experimental
General
Chemicals were purchased from Aldrich Chemical
Company. Solvents for extraction and chromatography
were technical grade. All solvents used in reactions were
freshly distilled from appropriate drying agents before use.
All other reagents were recrystallized or distilled as neces-
sary. All reactions were performed under an atmosphere of
dry nitrogen. Analytical TLC was performed with Merck
Scheme 5.

F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
6323
silica gel 60 F254 plates. Visualization was accomplished by
UV light and KMnO4 solution. Flash chromatography was
carried out using Merck silica gel 60 (230±400 mesh
ASTM). Melting points were determined with an Electro-
thermal IA9100 Digital Melting Point Apparatus and are
Tetraethyl (E)-N-(2-allyloxybenzyliden)aminomethyldi-
phosphonate (3c). Starting from 6.4 mmol of 2-allyloxy-
benzaldehyde, 2 g (70%) were obtained; H NMR (d) 8.72
1
4
(t, 1H, JHPˆ4.3 Hz, CHvN), 7.96±6.83 (m, 4H, Ph±H),
6.12±5.91 (m, 1H, CH2vCH), 5.37 (dd, 1H, 3JHHˆ17.2 Hz,
1
3
uncorrected. H (300 MHz), 13C (75 MHz) and 31P NMR
4JHHˆ1.3 Hz, OCH2CHvCHtrans), 5.26 (dd, 1H, JHH
ˆ
4
(120 MHz) spectra were recorded on a Varian UnityPlus
300 MHz spectrometer using CDCl3 solutions with TMS
10.5 Hz, JHHˆ1.3 Hz, OCH2CHvCHcis), 4.53 (dd, 2H,
3JHHˆ5.2 Hz, JHHˆ1.3 Hz, OCH2CHvCH2), 4.32 (t, 1H,
4
1
as an internal reference for H and 13C NMR spectra and
2JHPˆ18.3 Hz, CHP), 4.17 (m, 8H, 4£OCH2CH3), 1.27 (m,
12H, 4£CH3); 13C NMR (d) 163.1 (t, 3JCPˆ15.4 Hz, CvN),
157.6 (Carom±C), 132.3 (±CHvCH2), 127.9, 127.0
(Carom±H), 123.6 (Carom±C), 120.4 (Carom±H), 117.2
(vCH2), 111.9 (Carom±H), 68.6 (OCH2CHvCH2), 68.1
phosphoric acid (85%) for 31P NMR spectra. Chemical
shifts (d) are reported in ppm and coupling constants (J)
are reported in Hertz. Low-resolution mass spectra (MS)
were obtained at 50±70 eV by electron impact (EIMS) on
a Hewlett±Packard 5971 spectrometer. Data are reported in
the form m/z (intensity relative to baseˆ100). Infrared
spectra (IR) were recorded on a Nicolet IRFT Magna 550
1
(t, JCPˆ149.6 Hz, CHP), 63.4, 63.3, 63.1, 63.0
(4£OCH2CH3), 16.1, 15.9 (2£CH3); 31P NMR (d) 15.8;
IR (NaCl, nmax) 1623 (CvN), 1300 (PvO), 1023
(P±O); EIMS m/z 447 (M1, 5). Anal. Calcd for
C19H31NO7P2: C, 51.01; H, 6.98; N, 3.13. Found: C,
51.25; H, 6.80; N, 3.10.
spectrometer for neat oils. Peaks are reported in cm21
.
Elemental analyses were performed in a LECO CHNS-
932 apparatus. Aminomethyldiphosphonate tetraethyl ester
6 was synthesized according to the literature procedure.9
Tetraethyl (E)-N-(2-pyridylmethyliden)aminomethyldi-
phosphonate (3d). Starting from 2.5 mmol of 2-pyridine-
carbaldehyde, 0.9 g (92%) were obtained; 1H NMR (d) 8.33
General procedure for the preparation of
iminophosphonates 3
4
(t, 1H, JHPˆ4.2 Hz, CHvN), 8.57±7.24 (m, 4H, Pyr±H),
2
4.37 (t, 1H, JHPˆ18.0 Hz, CHP), 4.18 (m, 8H, 4£CH2),
3
A carbonyl compound (aldehyde or ketone, about 6 mmol)
was added to a solution of an equimolecular amount of
aminomethyldiphosphonate tetraethyl ester in dry benzene
(20 mL) and the stirred mixture was heated at re¯ux in a
Dean±Stark for 4 h. The solvent was removed at reduced
pressure and the crude product was puri®ed by ¯ash
chromatography eluting with ethyl acetate to provide the
pure compounds as yellow±orange oils.
1.27 (m, 12H, 4£CH3); 13C NMR (d) 168.2 (t, JCPˆ
15.0 Hz, CvN), 153.5 (CPyr±C), 149.2, 136.4, 125.2,
1
121.1 (CPyr±H), 67.9 (t, JCPˆ149.0 Hz, CHP), 63.4, 63.3,
63.2, 63.1 (4£CH2), 16.2, 16.1 (2£CH3); 31P NMR (d) 15.3;
IR (NaCl, nmax) 1650 (CvN), 1250 (PvO), 1050 (P±O);
EIMS m/z 347 (M12OCH2CH3, 3). Anal. Calcd for
C15H26N2O6P2: C, 45.91; H, 6.68; N, 7.14. Found: C,
46.00; H, 6.60; N, 7.10.
Tetraethyl (E)-N-(benzyliden)aminomethyldiphospho-
nate (3a). Starting from 6.6 mmol of benzaldehyde, 1.5 g
Tetraethyl (E)-N-(3-pyridylmethyliden)aminomethyldi-
phosphonate (3e). Starting from 2.5 mmol of 3-pyridin-
carbaldehyde, 0.5 g (70%) were obtained; H NMR (d)
1
4
1
(60%) were obtained; H NMR (d) 8.28 (t, 1H, JHPˆ
4.2 Hz, CHvN), 7.20±7.84 (m, 5H, Harom), 4.30 (t, 1H,
2JHPˆ18.0 Hz, CHP), 4.20 (m, 8H, 4£CH2),1.27 (m, 12H,
3
8.86 (s, 1H, CHvNPyr), 8.63 (d, 1H, JHHˆ3.3 Hz, Pyr±
4
H), 8.32 (t, 1H, JHPˆ4.2 Hz, CHvN), 8.10 (dd, 1H,
3
4
4£CH3); 13C NMR (d) 167.3 (t, JCPˆ15.3 Hz, CvN),
3JHHˆ6.0 and JHHˆ1.5 Hz, Pyr±H), 7.30 (m, 1H, Pyr±
2
135.2 (Carom±C), 131.4, 131.2, 128.4, 128.2 and 128.0
H), 4.30 (t, 1H, JHPˆ18.0 Hz, CHP), 4.20 (m, 8H,
1
(Carom±H), 67.9 (t, JCPˆ149, CHP), 63.4, 63.3, 63.2,
4£CH2), 1.27 (m, 12H, 4£CH3); 13C NMR (d) 164.5 (t,
3JCPˆ15.6 Hz, CvN), 151.8 (CPyr±N), 149.8 (CPyr±H),
134.6 (CPyr±H), 130.7 (CPyr±C), 123.39 (CPyr±H), 67.8 (t,
1JCPˆ149.0 Hz, CHP), 63.4, 63.3, 63.2, 63.1 (4£CH2), 16.2,
16.1 (2£CH3); 31P NMR (d) 15.4; IR (NaCl, nmax) 1630
(CvN), 1250 (PvO), 1050 (P±O); EIMS m/z 392 (M1,
2). Anal. Calcd for C15H26N2O6P2: C, 45.91; H, 6.68; N,
7.14. Found: C, 46.10; H, 6.55; N, 7.05.
63.1 (4£CH2), 16.2, 16.1 (2£CH3); 31P NMR (d) 15.8; IR
(NaCl, nmax) 1629 (CvN), 1257 (PvO), 1030 (P±O);
EIMS m/z 288 (M12NCC6H5, 100). Anal. Calcd for
C16H27NO6P2: C, 49.10; H, 6.92; N, 3.55. Found: C,
49.20; H, 6.90; N, 3.65.
Tetraethyl (E)-N-(4-methylbenzyliden)aminomethyldi-
phosphonate (3b). Starting from 6.2 mmol of p-tolualde-
hyde, 2.2 g (87%) were obtained; 1H NMR (d) 8.25 (t, 1H,
Tetraethyl (E)-N-(2-thiophenemethyliden)aminomethyl-
diphosphonate (3f). Starting from 2.5 mmol of 2-thio-
phenylcarbaldehyde, 0.5 g (70%) were obtained; H NMR
3
4JHPˆ4.2 Hz, CHvN), 7.63 (d, 2H, JHHˆ9.1 Hz, Ph±H),
3
2
1
7.18 (d, 2H, JHHˆ9.1 Hz, Ph±H), 4.31 (t, 1H, JHPˆ
18.3 Hz, CHP), 4.20 (m, 8H, 4£CH2), 2.35 (s, 3H,
PhCH3), 1.30 (m, 12H, 4£CH3); 13C NMR (d) 167.5 (t,
3JCPˆ15.1 Hz, CvN), 141.9 and 132.9 (Carom±C), 129.3
4
(d) 8.38 (t, 1H, JHPˆ4.1 Hz, CHvN), 7.79±7.01 (m, 3H,
2
TioPh±H), 4.34 (t, 1H, JHPˆ18.5 Hz, CHP), 4.20 (m, 8H,
4£CH2), 1.28 (m, 12H, 4£CH3); 13C NMR (d) 160.3 (t,
1
and 128.5 (Carom±H), 68.05 (t, JCPˆ149.5 Hz, CHP),
3JCPˆ15.8 Hz, CvN), 134.3 (CThio±C), 131.9, 130.2,
1
63.6, 63.5, 63.4, 63.3, 63.2 (6£CH2), 21.5 (PhCH3), 16.4,
16.1 (2£CH3); 31P NMR (d) 16.0; IR (NaCl, nmax) 1632
(CvN), 1261 (PvO), 1029 (P±O); EIMS m/z 288
(M12NCC6H4CH3, 100). Anal. Calcd for C17H29NO6P2:
C, 50.37; H, 7.21; N, 3.46. Found: C, 50.25; H, 7.45; N,
3.50.
127.4 (CThio±H), 67.2 (t, JCPˆ148.6 Hz, CHP), 63.4,
63.4, 63.2, 63.1 (4£CH2), 16.2, 16.1 (CH3); 31P NMR (d)
15.4; IR (NaCl, nmax) 1630 (CvN), 1250 (PvO), 1050
(P±O); EIMS m/z 288 (M12NCC4H3S, 100). Anal. Calcd
for C14H25NO6P2S: C, 42.32; H, 6.34; N, 3.52; S, 8.07.
Found: C, 42.25; H, 6.25; N, 3.45; S, 8.00.

6324
F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
Tetraethyl (E)-N-(3-phenylprop-2-enyliden)aminomethyl-
diphosphonate (3g). Starting from 2.4 mmol of cinnamal-
dehyde, 0.7 g (70%) were obtained; H NMR (d) 8.00 (m,
ture until evolving of gas (H2) ceased thus ensuring that
NaBH(OAc)3 formation had taken place. Then dry aceto-
nitrile (5 mL) was added, the reaction vessel cooled to 08C,
the imine 3 (1±1.5 mmol) added and the reaction stirred for
1 h at 08C. Acetic acid and acetonitrile were removed at
reduced pressure and the crude product was puri®ed by
¯ash chromatography eluting with ethyl acetate to provide
the pure compounds as yellow±orange oils (see Table 4).
1
1H, CHvN), 6.97±7.44 (m, 7H, Ph±H, ±CHvCH±), 4.25
(m, 9H, 4£CH2, CHP), 1.27 (m, 12H, 4£CH3); 13C NMR (d)
169.2 (t, 3JCPˆ15.4 Hz, CvN), 143.8 (Ph±CHvCH), 135.2
1
(Ph±CH), 129.6±127.5 (Carom), 67.0 (t, JCPˆ149.5 Hz,
CHP), 63.2 (CH2), 16.1 (CH3); 31P NMR (d) 16.0; IR
(NaCl, nmax) 1633 (CvN), 1255 (PvO), 1036 (P±O);
EIMS m/z 314 (M12Ph±CHvCH, 1). Anal. Calcd for
C18H29NO6P2: C, 51.80; H, 7.00; N, 3.36. Found: C,
51.70; H, 6.90; N, 3.45.
Tetraethyl N-(4-methylbenzyl)aminomethyldiphospho-
nate (8a). According to general procedure, imine 3b
(0.5 g, 1.23 mmol), NaBH4 (0.13 g, 3.42 mmol), glacial
acetic acid (3 mL) and dry acetonitrile (5 mL) were used.
The crude residue was puri®ed by ¯ash chromatography to
yield 0.3 g (60%) of 8a; 1H NMR (d) 7.18 (d, 2H,
Tetraethyl N-(cycloheptyliden)aminomethyldiphospho-
nate (3h). Starting from 3.6 mmol of cycloheptanone, 1 g
2
(70%) was obtained; 1H NMR (d) 4.55 (t, 1H, JHPˆ
3JHHˆ7.9 Hz, Ph±H), 7.06 (d, 2H, JHHˆ7.9 Hz, Ph±H),
3
18.6 Hz, CHP), 4.11 (m, 8H, 4£OCH2), 2.50 (m, 4H,
4.15 (m, 8H, 4£OCH2), 3.93 (s, 2H, NCH2), 3.25 (t, 1H,
2JHPˆ21.3 Hz, CHP), 2.27 (s, 3H, PhCH3), 2.12 (s, 1H, NH),
1.28 (m, 12H, 4£CH3); 13C NMR (d) 136.7, 135.4
(2£Carom±C), 128.7±128.3 (Carom±H), 62.4, 54.6
2£CH2), 1.51 (m, 8H, 4£CH2), 1.27 (m, 12H, 4£CH3);
3
13C NMR (d) 182.1 (t, JCPˆ15.1 Hz, CvN), 63.3, 63.2,
1
62.9, 62.8 (4£OCH2), 58.8 (t, JCPˆ153.5 Hz, CHP), 53.5,
1
48.8, 31.4, 29.6, 26.4, 24.3 (6£CH2), 16.2, 16.1, 15.8, 15.7
(4£CH3); 31P NMR (d) 16.9; IR (NaCl, nmax) 1633 (CvN),
1248 (PvO), 1029 (P±O); EIMS m/z 397 (M1, 2). Anal.
Calcd for C16H33NO6P2: C, 48.36; H, 8.37; N, 3.52. Found:
48.50; H, 8.25; N, 3.45.
(2£CH2), 53.1 (t, JCPˆ146.0 Hz, CHP), 20.7 (PhCH3),
16.1 (CH3); 31P NMR (d) 20.0; IR (NaCl, nmax) 3489
(NH), 1248 (PvO), 1029 (P±O); EIMS m/z 288
(M12CH3PhCH2NH, 100). Anal. Calcd for C17H31NO6P2:
C, 50.12; H, 7.67; N, 3.44. Found: C, 50.25; H, 7.75; N,
3.55.
Tetraethyl
N-(norborn-2-yliden)aminomethyldiphos-
phonate (3i). Starting from 3.3 mmol of norbornan-2-one,
0.8 g (60%) were obtained; 1H NMR (d) 4.50 (t, 1H,
2JHPˆ18.5 Hz, CHP), 4.11 (m, 8H, 4£OCH2), 2.18±1.66
(m, 10H, 4£CH2, 2£CHnorbor), 1.27 (m, 12H, 4£CH3); 13C
Tetraethyl N-(2-pyridylmethyl)aminomethyldiphospho-
nate (8b). According to general procedure, imine 3d
(0.5 g, 1.27 mmol), NaBH4 (0.14 g, 3.68 mmol), glacial
acetic acid (3 mL) and dry acetonitrile (5 mL) were used.
The crude residue was puri®ed by ¯ash chromatography to
yield 0.2 g (40%) of 8b; 1H NMR (d) 8.48 (d, 1H,
3
NMR (d) 187.2 (t, JCPˆ14.6 Hz, CvN), 62.6, 62.5, 62.4,
1
62.3 (4£OCH2), 56.3 (t, JCPˆ152.3 Hz, CHP), 42.8 (CH),
3
32.9 (CH2), 32.5 (CH2), 30.5 (CH), 21.4, 19.4 (2£CH2),
3JHHˆ4.8 Hz, Pyr±H), 7.60 (t, 1H, JHHˆ5.0 Hz, Pyr±H),
16.1, 15.8 (2£CH3); 31P NMR (d) 16.8; IR (NaCl, nmax
)
7.35 (d, 1H, JHHˆ7.8 Hz, Pyr±H), 7.10 (t, 1H, JHH
ˆ
3
3
1666 (CvN), 1255 (PvO), 1023 (P±O); EIMS m/z 395
(M1, 8). Anal. Calcd for C16H31NO6P2: C, 48.61; H, 7.90;
N, 3.54. Found: 48.70; H, 7.75; N, 3.45.
6.1 Hz, Pyr±H), 4.15 (m, 8H, 4£CH2), 4.11 (s, 2H,
2
NCH2), 3.40 (t, 1H, JHPˆ21.3 Hz, CHP), 2.85 (br s, 1H,
NH), 1.27 (m, 12H, 4£CH3); 13C NMR (d) 158.6 (CPyr±C),
148.8, 136.1, 122.1, 121.8 (CPyr±H), 62.4, 54.6 (2£CH2),
1
Tetraethyl N-[bis(ethoxycarbonyl)methyliden]amino-
methyldiphosphonate (3j). Diethyl ketomalonate (0.56 g,
3.23 mmol) and molecular sieve (0.4 nm) were added to a
solution of aminomethyldiphosphonate tetraethyl ester
(0.98 g, 3.23 mmol) in dry dichloromethane (10 mL) and
the stirred mixture was heated at re¯ux for 12 h. The solvent
was removed at reduced pressure and the crude product was
puri®ed by ¯ash chromatography eluting with ethyl acetate
to provide 1.5 g (40%) of the compound as a yellow oil; 1H
53.1 (t, JCPˆ146.0 Hz, CHP), 16.1 (CH3); 31P NMR (d)
19.8; IR (NaCl, nmax) 3456 (NH), 1235 (PvO), 1016
(P±O); EIMS m/z 394 (M1, 2). Anal. Calcd for
C15H28N2O6P2: C, 45.69; H, 7.16; N, 7.10. Found: C,
45.55; H, 7.10; N, 7.15.
Tetraethyl N-(cycloheptyl)aminomethyldiphosphonate
(8c). According to general procedure, imine 3h (0.49 g,
1.23 mmol), NaBH4 (0.13 g, 3.42 mmol), glacial acetic
acid (3 mL) and dry acetonitrile (5 mL) were used. The
crude residue was puri®ed by ¯ash chromatography to
yield 0.35 g (71%) of 8c; 1H NMR (d) 4.11 (m, 8H,
2
NMR (d) 5.20 (t, 1H, JHPˆ17.1 Hz, CHP), 4.33 (m, 12H,
6£CH2), 1.30 (m, 18H, 6£CH3); 13C NMR (d) 168.4
(CO2Et), 168.1 (CvN), 64.1, 63.8, 63.7, 63.3, 62.6, 62.5
1
2
(6£CH2), 47.1 (t, JCPˆ150.0 Hz, CHP), 16.3, 16.2, 13.9,
4£OCH2), 3.30 (t, 1H, JHPˆ21.9 Hz, CHP), 2.91 (m, 1H,
13.8 (4£CH3); 31P NMR (d) 12.9; IR (NaCl, nmax) 1739
(CvN), 1248 (PvO), 1023 (P±O); EIMS m/z 288
(M12NCC6H10O4, 100). Anal. Calcd for C16H31NO10P2:
C, 41.83; H, 6.80; N, 3.05. Found: C, 42.00; H, 6.70; N,
3.10.
CHNH), 2.10 (br s, 1H, NH), 1.72 (m, 4H, 2£CH2), 1.52 (m,
8H, 4£CH2), 1.27 (m, 12H, 4£CH3); 13C NMR (d) 62.8,
1
62.2 (2£OCH2), 57.7 (CH±NH), 51.1 (t, JCPˆ145.5 Hz,
CHP), 33.8, 27.9, 23.4 (3£CH2), 15.9 (CH3); 31P NMR (d)
20.1; IR (NaCl, nmax) 3482 (NH), 1241 (PvO), 1023
(P±O); EIMS m/z 399 (M1, 1). Anal. Calcd for
C16H35NO6P2: C, 48.12; H, 8.83; N, 3.51. Found: C,
48.00; H, 8.80; N, 3.50.
Synthesis of aminoalkylphosphonates 8
General procedure: NaBH4 (3±4 mmol) was added over
glacial acetic acid (3 mL) at about 158C under inert atmos-
phere and the resulting mixture was stirred at room tempera-
Tetraethyl N-(norborn-2-yl)aminomethyldiphosphonate
(8d). According to general procedure, imine 3i (0.45 g,

F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
6325
1.23 mmol), NaBH4 (0.14 g, 3.68 mmol), glacial acetic acid
(3 mL) and dry acetonitrile (5 mL) were used. The crude
residue was puri®ed by ¯ash chromatography to yield
(0.31 mL, 2.5 mmol) and an equimolecular amount of
base (BTPP and KtBuO) were used (see Table 2). The
crude residue was puri®ed by ¯ash chromatography eluting
with hexane to yield 0.4 g (50%, from BTPP) and 2.45 g
(0.44 g, from KtBuO) of 4ab as a pale yellow oil; 1H NMR
(d) 8.60 (s, 1H, CHvN), 7.07±7.80 (m, 9H, Ph±H), 7.05 (d,
1H, 3JHPˆ16.8 Hz, CHvC), 4.15 (m, 4H, 2£CH2), 2.27 (s,
1
0.3 g (67%) of 8d; H NMR (d) 4.11 (m, 8H, 4£OCH2),
2
3.28 (m, CHNH), 3.20 (t, 1H, JHPˆ21.6 Hz, CHP), 1.66±
2.18 (m, 10H, 4£CH2, 2£CHnorbor), 1.27 (m, 12H, 4£CH3);
13C NMR (d) 62.9, 62.5 (OCH2), 58.9 (CHN), 52.7 (t,
1JCPˆ145.0 Hz, CHP), 39.5 (CH), 37.7, 36.8 (2£CH2),
36.6 (CH), 29.9, 20.3 (2£CH2), 16.1 (CH3); 31P NMR (d)
20.4; IR (NaCl, nmax) 3469 (NH), 1241 (PvO), 1016 (P±
O); EIMS m/z 397 (M1, 1). Anal. Calcd for C16H33NO6P2:
C, 48.36; H, 8.37; N, 3.52. Found: C, 48.25; H, 8.40; N,
3.55.
3
3H, PhCH3), 1.26 (t, 6H, JHHˆ7.0 Hz, 2£CH3); 13C NMR
(d) 162.1 (d, 3JCPˆ9.6 Hz, CvN), 138.7 (Carom±C), 135.8
1
(d, JCPˆ175.7 Hz, CvCP), 134.3, 136.1 (Carom±C),
2
3
132.4 (d, JCPˆ22.2 Hz, CvCP), 131.7 (d, JCPˆ19.1 Hz,
Carom±C), 131.3, 131.2, 128.8, 128.1, 128.6 (Carom±H),
62.0 (CH2), 21.1 (PhCH3), 16.1 (CH3); 31P NMR (d) 14.4;
IR (NaCl, nmax) 1612 (CvN), 1245 (PvO), 1028 (P±O);
EIMS m/z 357 (M1, 100). Anal. Calcd for C20H24NO3P: C,
67.22; H, 6.77; N, 3.92. Found: C, 67.15; H, 6.8; N, 3.85.
Synthesis of azadienes 4 and azatrienes 9 and 10
General procedure A: Base (MeLi, BuLi, KtBuO or BTPP)
(about 6 mmol) was added to a solution of an equimolecular
amount of imine 3 in dry THF (10 mL) at 2788C. After 1 h
the aldehyde was added, the mixture was allowed to warm
to room temperature and stirred overnight. The solvent was
removed at reduced pressure and the crude product was
puri®ed by ¯ash chromatography eluting with the appro-
priate solvent to provide the pure compounds as yellow±
orange oils (see Table 2).
(1E,3E)-3-(Diethoxyphosphoryl)-1,4-diphenyl-2-azabuta-
1,3-diene 4ac. According to general procedure A, imine 3a
(2.6 g, 6.7 mmol), benzaldehyde (0.68 mL, 6.7 mmol) and
BTPP (2.1 mL, 6.87 mmol) were used. The crude residue
was puri®ed by ¯ash chromatography eluting with hexane/
ethyl acetate 15:1 to yield 1 g (45%) of 4ac. According to
general procedure B, imine 3a (2.5 g, 6.4 mmol), benzalde-
hyde (0.7 mL, 7 mmol) and Cs2CO3 (2.7 g, 8.3 mmol) were
used. The crude residue was puri®ed by ¯ash chroma-
tography eluting with hexane/ethyl acetate 10:1 to yield
Synthesis of azadienes 4 and azatrienes 9 and 10
1
1.4 g (65%) of 4ac as a pale yellow oil; H NMR (d) 8.58
(s, 1H, CHvN), 7.20±7.80 (m, 10H, Ph±H), 7.01 (d, 1H,
3JHPˆ16.8 Hz, CHvC), 4.15 (m, 4H, 2£CH2), 1.25 (t, 6H,
3JHHˆ7.1 Hz, 2£CH3); 13C NMR (d) 162.6 (d, 3JCPˆ9.8 Hz,
General procedure B: Excess of Cs2CO3 (about 5 mmol)
was added to a solution of imine 3 (about 4 mmol) and
aldehyde (about 4 mmol) in THF/i-PrOH (4:1, 10 mL) at
room temperature. The mixture was stirred for 1 to 4
days. The solvent was removed at reduced pressure and
then dichloromethane was added, the organic layer washed
with water (3£25 mL), dried over MgSO4 and concentrated.
The residue was puri®ed by ¯ash chromatography eluting
with the appropriate solvent to provide the pure compounds
as yellow±orange oils (see Table 2).
1
3
CvN), 137.0 (d, JCPˆ175.4 Hz, CvCP), 134.6 (d, JCPˆ
2
19.1 Hz, Carom±C), 132.4 (d, JCPˆ21.6 Hz, CvCP),
132.1±128.0 (Carom), 61.9 (CH2), 16.1 (CH3); 31P NMR
(d) 14.0; IR (NaCl, nmax) 1619 (CvN), 1261 (PvO),
1035 (P±O); EIMS m/z 342 (M121, 100). Anal. Calcd
for C19H22NO3P: C, 66.46; H, 6.46; N, 4.08. Found: C,
66.55; H, 6.35; N, 4.15.
(1E,3E)-3-(Diethoxyphosphoryl)-1-phenyl-4-(ethoxycar-
bonyl)-2-azabuta-1,3-diene 4ad. According to general
procedure A, imine 3a (1.7 g, 4.3 mmol), ethyl glioxalate
(0.46 mL, 4.3 mmol) and BTPP (1.32 mL, 4.3 mmol) were
used. The crude residue was puri®ed by ¯ash chroma-
tography eluting with hexane/ethyl acetate 5:1 to yield
(1E,3E)-3-(Diethoxyphosphoryl)-4-methyl-1-phenyl-2-
azabuta-1,3-diene 4aa. According to general procedure A,
imine 3a (2.28 g, 5.8 mmol), acetaldehyde (0.33 mL,
5.8 mmol) and an equimolecular amount of base (MeLi,
BuLi and KtBuO) were used (see Table 2). The crude
residue was puri®ed by ¯ash chromatography eluting with
hexane/ethyl acetate 2:1 to yield 2.28 g (48%, from MeLi),
2.35 g (50%, from BuLi) and 2.45 g (55%, from KtBuO) of
4aa as a pale yellow oil; 1H NMR (d) 8.45 (s, 1H, CHvN),
1
0.7 g (50%) of 4ad as a pale yellow oil; H NMR (d) 8.15
(s, 1H, CHvN), 7.25±7.82 (m, 5H, Ph±H), 6.03 (d, 1H,
3JHPˆ18.2 Hz, CHvC), 4.20 (m, 4H, 2£CH2), 4.09 (m,
3
3
2H, CH2), 1.27 (t, 6H, JHHˆ7.0 Hz, 2£CH32), 1.10 (t, 3H,
7.22±7.83 (m, 5H, Ph±H), 6.42 (dq, 1H, JHHˆ7.0 Hz,
3JHHˆ6.9 Hz, CH3); 13C NMR (d) 164.3 (d, JCPˆ24.6 Hz,
3
3JHPˆ15.3 Hz, CHvC), 4.10 (q, 4H, JHHˆ7.1 Hz,
3
3
4
CvCP), 162.5 (d, JCPˆ11.6 Hz, CvN), 154.6 (d,
2£CH2), 1.89 (dd, 3H, JHHˆ7.0 Hz, JHPˆ3.2 Hz, CH3),
1JCPˆ109.3 Hz, CvCP), 134.9 (Carom±C), 128.6±130.4
(Carom), 63.3, 60.3 (CH2), 16.1, 13.9 (2£CH3); 31P NMR
(d) 9.4; IR (NaCl, nmax) 1646 (CvN), 1268 (PvO), 1023
(P±O); EIMS m/z 339 (M1, 1). Anal. Calcd for
C16H22NO5P: C, 56.63; H, 6.54; N, 4.13. Found: C, 56.60;
H, 6.45; N, 4.10.
3
1.27 (t, 6H, JHHˆ7.0 Hz, 2£CH3); 13C NMR (d) 161.6 (d,
1
3JCPˆ9.5 Hz, CvN), 139.2 (d, JCPˆ181.8 Hz, CvCP),
2
136.1 (Carom±C), 134.3 (d, JCPˆ24.2 Hz, CvCP),
131.2, 128.7, 128.4 (Carom±H), 62.0 (CH2), 16.2 (CH3),
3
12.8 (d, JCPˆ14.1 Hz, CH3); 31P NMR (d) 13.5; IR
(NaCl, nmax) 1622 (CvN), 1248 (PvO), 1023 (P±O);
EIMS m/z 281 (M1, 100). Anal. Calcd for C14H20NO3P:
C, 59.78; H, 7.17; N, 4.98. Found: 59.85; H, 7.05; N, 5.05.
(1E,3E)-3-(Diethoxyphosphoryl)-1,4-bis(4-methylphenyl)-
2-azabuta-1,3-diene 4ba. According to general procedure
A, imine 3b (2 g, 5 mmol), p-tolualdehyde (0.6 mL,
5 mmol) and MeLi (1.6 M, 3.2 mL) were used. The crude
residue was puri®ed by ¯ash chromatography eluting with
(1E,3E)-3-(Diethoxyphosphoryl)-4-(4-methylphenyl)-1-
phenyl-2-azabuta-1,3-diene 4ab. According to general
procedure A, imine 3a (1 g, 2.5 mmol), p-tolualdehyde

6326
F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
hexane/ethyl acetate 15:1 to yield 0.87 g (47%) of 4ba.
According to general procedure B, imine 3b (1.7 g,
4.2 mmol), p-tolualdehyde (0.5 mL, 4.5 mmol) and
Cs2CO3 (1.8 g, 5.4 mmol) were used. The crude residue
was puri®ed by ¯ash chromatography eluting with hexane/
ethyl acetate 10:1 to yield 1.07 g (67%) of 4ba as a pale
4.3 mmol) were used. The crude residue was puri®ed by
¯ash chromatography in alumina eluting with hexane/
ethyl acetate 3:1 to yield 0.4 g (50%) of 4bd as a pale yellow
oil; 1H NMR (d) 8.94 (s, 1H, Pyr±H), 8.56 (s, 1H, CHvN),
3
8.42 (d, 1H, JHHˆ4.8 Hz, Pyr±H), 8.05 (d, 1H,
3JHHˆ8.1 Hz, Pyr±H), 7.80±7.18 (m, 4H, Ph±H), 7.10 (m,
1
3
yellow oil; H NMR (d) 8.56 (s, 1H, CHvN), 7.09±7.70
1H, Pyr±H), 7.03 (d, 1H, JHPˆ16.8 Hz, CHvC) 4.14 (m,
3
(m, 8H, Ph±H), 7.05 (d, 1H, JHPˆ16.6 Hz, CHvC), 4.11
4H, 2£CH2), 2.37 (s, 3H, PhCH3), 1.27 (t, 6H, 3JHHˆ7.1 Hz,
2£CH3); 13C NMR (d) 163.2 (d, 3JCPˆ9.5 Hz, CvN), 151.8
(CPyr), 148.7 (CPyr), 142.6 (Carom±C), 138.2 (CPyr), 137.9
(m, 4H, 2£CH2), 2.35 (s, 3H, PhCH3), 2.26 (s, 3H, PhCH3),
3
1.26 (t, 6H, JHHˆ7.1 Hz, 2£CH3); 13C NMR (d) 162.1 (d,
3JCPˆ9.6 Hz, CvN), 138.7, 142.1 (Carom±C), 136.2 (d,
(d, JCPˆ167.2 Hz, CvCP), 133.3 (Carom±C), 130.9±
1
1JCPˆ175.2 Hz, CvCP), 133.7 (Carom±C), 132.6 (d,
127.3 (Carom±H), 123.1 (CPyr±H), 115.3 (d, JCPˆ
2
3
2JCPˆ22.7 Hz, CvCP), 131.9 (d, JCPˆ19.1 Hz, Carom±
18.6 Hz, CvCP), 62.5 (CH2), 21.5 (PhCH3), 16.2 (CH3);
31P NMR (d) 13.0; IR (NaCl, nmax) 1659 (CvN), 1427
(PvO), 1202 (P±O); EIMS m/z 357 (M1, 50). Anal.
Calcd for C19H23N2O3P: C, 63.68; H, 6.47; N, 7.82.
Found: C, 63.75; H, 6.50; N, 7.85.
C), 131.3, 129.4, 128.9, 128.7 (Carom±H), 62.1 (CH2),
21.5, 21.3 (2£PhCH3), 16.2 (CH3); 31P NMR (d) 14.3; IR
(NaCl, nmax) 1608 (CvN), 1247 (PvO), 1023 (P±O);
EIMS m/z 371 (M1, 100). Anal. Calcd for C21H26NO3P: C,
67.91; H, 7.06; N, 3.77. Found: C, 68.05; H, 7.10; N, 3.80.
(1E,3E)-3-(Diethoxyphosphoryl)-4-(4-nitrophenyl)-1-(2-
allyloxyphenyl)-2-azabuta-1,3-diene 4ca. According to
general procedure A, imine 3c (2.64 g, 5.91 mmol), p-nitro-
benzaldehyde (0.91 g, 6 mmol) and BuLi (1.6 M, 3.8 mL)
were used. The crude residue was puri®ed by ¯ash chroma-
tography eluting with hexane/ethyl acetate 15:1 to yield
0.79 g (30%) of 4ca. According to general procedure B,
imine 3c (2.7 g, 6.04 mmol), p-nitrobenzaldehyde (0.94 g,
6.2 mmol) and Cs2CO3 (2.02 g, 6.2 mmol) were used. The
crude residue was puri®ed by ¯ash chromatography eluting
with hexane/ethyl acetate 10:1 to yield 1.61 g (60%) of 4ca
(1E,3E)-3-(Diethoxyphosphoryl)-1-(4-methylphenyl)-2-
azabuta-1,3-diene 4bb. According to general procedure A,
formaldehyde was bubbled into the solution of imine 3b
(0.95 g, 2.42 mmol) and BTPP (0.74 mL, 2.42 mmol). The
crude (0.5 g, 80%) could not be puri®ed by crystallization,
by ¯ash chromatography or distillation and was used as
1
obtained; H NMR (d) 8.25 (s, 1H, CHvN), 7.63 (d, 2H,
3
3JHHˆ8.1 Hz, Ph±H), 7.17 (d, 2H, JHHˆ7.8 Hz, Ph±H),
3
5.38 (d, 1H, JHPˆ14.7 Hz, CHvCcis), 5.52 (d, 1H,
3JHPˆ39.3 Hz, CHvCtrans), 4.10 (m, 4H, 2£CH2), 2.35
3
1
(s, 3H, PhCH3), 1.26 (t, 6H, JHHˆ7.0 Hz, 2£CH3); 13C
as a pale yellow oil; H NMR (d) 8.50 (s, 1H, CHvN),
3
3
NMR (d) 161.3 (d, JCPˆ12.5 Hz, CvN), 150.1 (d,
7.10±8.00 (m, 8H, Ph±H), 7.05 (d, 1H, JHPˆ16.8 Hz,
1JCPˆ193.8 Hz, CvCP), 141.9, 132.8 (Carom±C), 129.1,
CHvCP), 6.00±6.10 (m, 1H, CH2vCH), 5.42 (dd, 1H,
2
4
128.5 (Carom±H), 115.0 (d, JCPˆ19.6 Hz, CvCP), 62.0
3JHHˆ17.2 Hz, JHHˆ1.3 Hz, OCH2CHvCHtrans), 5.30
3
4
(CH2), 21.5 (PhCH3), 16.2 (CH3); 31P NMR (d) 12.1; IR
(NaCl, nmax) 1659 (CvN), 1235 (PvO), 1069 (P±O);
EIMS m/z 281 (M1, 100). Anal. Calcd for C14H20NO3P:
C, 59.78; H, 7.17; N, 4.98. Found: C, 59.85; H, 7.20; N,
5.05.
(dd, 1H, JHHˆ10.5 Hz, JHHˆ1.3 Hz, OCH2CHvCHcis),
4.60 (dd, 2H, 3JHHˆ5.1 Hz, 4JHHˆ1.3 Hz, OCH2CHvCH2),
3
4.20 (q, 4H, JHHˆ7.2 Hz, 2£OCH2CH3), 1.26 (t, 6H,
3JHHˆ7.0 Hz, 2£CH3); 13C NMR (d) 159.9 (d,
3JCPˆ9.0 Hz, CvN), 159.1 (Carom±O), 142.7 (d,
1JCPˆ176.5 Hz, CvCP), 141.1 (Carom±NO2), 133.6
2
(1E,3E)-3-(Diethoxyphosphoryl)-1-(4-methylphenyl)-4-
(2-pyridyl)-2-azabuta-1,3-diene 4bc. According to general
procedure B, imine 3b (1.3 g, 3.3 mmol), 2-pyridinecarb-
aldehyde (0.3 mL, 3.6 mmol) and Cs2CO3 (1.37 g,
4.3 mmol) were used. The oily crude (0.4 g, 50%) could
not be puri®ed by crystallization, by ¯ash chromatography
(±CHvCH2), 128.5 (d, JCPˆ19.1 Hz, CvCP), 131.5±
121.2 (Carom), 117.7 (vCH2), 69.5 (OCH2CHvCH2),
62.5 (OCH2CH2), 16.2 (CH3); 31P NMR (d) 12.6; IR
(NaCl, nmax) 1595 (CvN), 1534 (NO2), 1242 (PvO),
1016 (P±O); EIMS m/z 414 (M1, 100). Anal. Calcd for
C22H25N2O6P: C, 59.46; H, 5.67; N, 6.30. Found: C,
59.35; H, 5.75; N, 6.25.
1
or distillation and was used as obtained; H NMR (d) 8.56
3
(br s, 1H, CHvNPyr), 8.36 (d, 1H, JHHˆ3.1 Hz, Pyr±H),
7.80±7.23 (m, 5H, Ph±H, Pyr±H), 7.10 (m, 1H, Pyr±H),
(1E,3E)-3-(Diethoxyphosphoryl)-1-(2-allyloxyphenyl)-2-
azapenta-1,3-diene 4cb. According to general procedure A,
imine 3c (1.2 g, 2.68 mmol), acetaldehyde (0.15 mL,
2.7 mmol) and BuLi (1.6 M, 1.7 mL) were used. The
crude residue was puri®ed by ¯ash chromatography eluting
with hexane/ethyl acetate 2:1 to yield 0.64 g (71%) of 4cb
3
7.03 (d, 1H JHPˆ16.8 Hz, CHvC), 4.14 (m, 4H, 2£CH2),
2.37 (s, 3H, PhCH3), 1.27 (m, 6H, 2£CH3); 13C NMR (d)
3
158.2 (d, JCPˆ22.1 Hz, CvN), 148.7, 147.7 (CPyr±H),
1
145.3 (CPyr±C), 138.1 (d, JCPˆ166.2 Hz, CvCP), 135.3
(Carom±C), 130.9±126.3 (Carom±H), 122.2, 119.1 (CPyr
±
2
1
H), 115.3 (d, JCPˆ15.6 Hz, CvCP), 62.5 (CH2), 21.5
as a pale yellow oil; H NMR (d) 8.50 (s, 1H, CHvN),
7.40±6.85 (m, 4H, Ph±H), 6.40 (dq, 1H, JHHˆ7.0 Hz,
3
(PhCH3), 16.2 (CH3); 31P NMR (d) 12.5; IR (NaCl, nmax
)
1640 (CvN), 1202 (PvO), 1036 (P±O); EIMS m/z 256
(M12CH3±Ph±CH, 100). Anal. Calcd for C19H23N2O3P:
C, 63.68; H, 6.47; N, 7.82. Found: C, 63.60; H, 6.55; N, 7.90.
4JHPˆ15.5 Hz, CHvCP), 5.98±6.03 (m, 1H, CH2vCH),
5.35 (dd, 1H, 3JHHˆ17.2 Hz, 4JHHˆ1.3 Hz, OCH2CHvCH-
3
4
trans), 5.24 (dd, 1H, JHHˆ10.5 Hz, JHHˆ1.3 Hz,
3
4
OCH2CHvCHcis), 4.54 (dd, 2H, JHHˆ5.2 Hz, JHH
ˆ
3
(1E,3E)-3-(Diethoxyphosphoryl)-1-(4-methylphenyl)-4-
(3-pyridyl)-2-azabuta-1,3-diene 4bd. According to
general procedure B, imine 3b (1.3 g, 3.3 mmol), 3-pyridin-
carbaldehyde (0.3 mL, 3.6 mmol) and Cs2CO3 (1.37 g,
1.3 Hz, OCH2CHvCH2), 4.07 (q, 4H, JHHˆ7.0 Hz,
3
3
2£OCH2CH3), 1.87 (dd, 3H, JHHˆ7.0 Hz, JHPˆ3.2 Hz,
vCHCH3), 1.25 (t, 6H, JHHˆ7.1 Hz, 2£CH2CH3); 13C
3
3
NMR (d) 158.0 (Carom±O), 157.5 (d, JCPˆ9.6 Hz,

F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
6327
1
2
CvN), 139.2 (d, JCPˆ181.3 Hz, CvCP), 133.5 (d, JCPˆ
14.8 Hz, CHvC), 4.06 (q, 4H, 3JHHˆ7.3 Hz, 2£CH2), 1.90
3
3
22.2 Hz, CvCP), 132.3, 132.2 (Carom, ±CHvCH2), 126.6,
124.6, 120.4 (Carom), 116.8 (vCH2), 111.9 (Carom), 68.4
(OCH2CHvCH2), 61.5 (OCH2CH2), 15.9 (CH3), 12.5 (d,
(dd, 3H, JHHˆ7.0 Hz, JHHˆ3.2 Hz, CH3), 1.26 (t, 6H,
3JHHˆ7.1 Hz, 2£CH3); 13C NMR (d) 154.4 (t, JCPˆ
3
1
9.6 Hz, CHvN), 143.4 (CThio±C), 138.3 (d, JCPˆ
3JCPˆ14.6 Hz, CH3); 31P NMR (d) 13.9; IR (NaCl, nmax
)
177.8 Hz, CHvC), 136.3 (d, JCPˆ22.7 Hz, CHvC),
2
1598 (CvN), 1246 (PvO), 1023 (P±O); EIMS m/z 337
(M1, 18). Anal. Calcd for C17H24NO4P: C, 60.53; H, 7.17;
N, 4.15. Found: C, 60.60; H, 7.10; N, 4.10.
127.6, 130.2, 131.9 (CThio±H), 62.0 (CH2), 16.2 (CH3),
3
13.1 (d, JCPˆ14.1 Hz, CH3); 31P NMR (d) 13.4; IR
(NaCl, nmax) 1630 (CvN), 1250 (PvO), 1050 (P±O);
EIMS m/z 287 (M1, 100). Anal. Calcd for C12H18NO3PS:
C, 50.16; H, 6.31; N, 4.88; S, 11.16. Found: C, 50.15; H,
6.25; N, 4.80; S, 11.15.
(1E,3E)-3-(Diethoxyphosphoryl)-4-(4-methylphenyl)-1-
(2-pyridyl)-2-azabuta-1,3-diene 4da. According to general
procedure B, imine 3d (0.9 g, 2.29 mmol), p-tolualdehyde
(0.3 mL, 2.5 mmol) and Cs2CO3 (0.96 g, 2.94 mmol) were
used. The crude residue was puri®ed by ¯ash chroma-
tography eluting with hexane/ethyl acetate 10:1 to yield
(1E,3E, 5E)-2-(Diethoxyphosphoryl)-6-phenyl-1-(4-nitro-
phenyl)-3-azahexa-1,3,5-triene 9. According to general
procedure A, imine 3g (0.65 g, 1.55 mmol), p-nitrobenz-
aldehyde (0.24 g, 1.59 mmol) and BTPP (0.48 mL,
1.57 mmol) were used. The crude residue was puri®ed by
¯ash chromatography eluting with hexane/ethyl acetate 15:1
to yield 0.3 g (59%) of 9. According to general procedure B,
imine 3g (2.7 g, 6.47 mmol), p-nitrobenzaldehyde (1.09 g,
7.2 mmol) and Cs2CO3 (2.7 g, 8.3 mmol) were used. The
crude residue was puri®ed by ¯ash chromatography eluting
with hexane/ethyl acetate 10:1 to yield a pale yellow oil.
This product was crystallized from hexane yielding 1.7 g
1
0.49 g (60%) of 4da as a yellow±orange oil; H NMR (d)
8.68 (s, 1H, CHvN), 8.66 (br d, 1H, 3JHHˆ4.8 Hz, Pyr±H),
3
8.11 (d, 1H, JHHˆ7.9 Hz, Pyr±H), 7.76 (bt, 1H,
3JHHˆ7.7 Hz, Pyr±H), 7.62 (d, 2H, JHHˆ8.1 Hz, Ph±H),
3
3
3
7.32 (dd, 1H, JHHˆ7.4 Hz, JHHˆ4.8 Hz, Pyr±H), 7.17 (d,
3
3
1H, JHPˆ16.5 Hz, CHvCP), 7.11 (d, 2H, JHHˆ8.4 Hz,
Ph±H), 4.15 (m, 4H, 2£CH2), 2.29 (s, 3H, PhCH3), 1.27
(t, 6H, JHHˆ7.2 Hz, 2£CH2CH3); 13C NMR (d) 162.8 (d,
3
3JCPˆ9.0 Hz, CvN), 149.7 (CPyr±H), 139.3 (Carom±C),
2
1
136.5 (CPyr±H), 135.3 (d, JCPˆ20.6 Hz, CvCP), 133.2
(64%) of 9 as a yellow solid; mp 95±968C, H NMR (d)
1
3
(d, JCPˆ172.0 Hz, CvCP), 125.5 (Carom±C), 131.6±
8.40 (d, 1H, JHHˆ8.4 Hz, CHvN), 8.15 (d, 2H,
3
129.0 (Carom), 125.1, 121.3 (CPyr±H), 62.2 (CH2), 21.3
)
3JHHˆ8.7 Hz, NO2±Ph±H), 7.84 (d, 2H, JHHˆ8.7 Hz,
(PhCH3), 16.2 (CH3); 31P NMR (d) 13.9; IR (NaCl, nmax
NO2±Ph±H), 7.58±7.32 (m, 5H, Ph±H), 7.16 (d, 1H,
3
1630 (CvN), 1400 (PvO), 1100 (P±O); EIMS m/z 359
(M1, 3). Anal. Calcd for C19H23N2O3P: C, 63.68; H, 6.47;
N, 7.82. Found: C, 63.70; H, 6.55; N, 7.80.
3JHHˆ15.9 Hz, PhCHvCH), 7.03 (dd, 1H, JHHˆ15.9 Hz,
3
3JHHˆ8.7 Hz, PhCHvCH), 7.00 (d, 1H, JHPˆ16.5 Hz,
3
CHvCP), 4.20 (q, 4H, JHHˆ7.2 Hz, 2£CH2), 1.26 (t, 6H,
3JHHˆ7.0 Hz, 2£CH3); 13C NMR (d) 165.7 (d,
(1E,3E)-3-(Diethoxyphosphoryl)-4-(4-methylphenyl)-1-
(3-pyridyl)-2-azabuta-1,3-diene 4ea. According to general
procedure B, imine 3e (0.8 g, 2.04 mmol), p-tolualdehyde
(0.2 mL, 2.23 mmol) and Cs2CO3 (0.85 g, 2.61 mmol) were
used. The crude residue was puri®ed by ¯ash chroma-
tography eluting with hexane/ethyl acetate 10:1 to yield
0.4 g (55%) of 4ea as a yellow±orange oil;.1H NMR (d)
8.94 (s, 1H, Pyr±H), 8.72 (s, 1H, CHvN), 8.66 (d, 1H,
3JCPˆ10.1 Hz, CvN), 146.9 (Carom±NO2), 146.1
1
(CvC±Ph), 141.7 (d, JCPˆ173.7 Hz, CvCP), 141.0 (d,
3JCPˆ19.6 Hz, Carom±CvCP), 135.5 (Carom±CvC),
2
131.6±123.6 (Carom), 128.6 (d, JCPˆ22.7 Hz, CvCP),
128.2 (CvC±Ph), 62.5 (CH2), 16.2 (CH3); 31P NMR (d)
12.6; IR (NaCl, nmax) 1627 (CvN), 1516 (NO2), 1246
(PvO), 1017 (P±O); EIMS m/z 414 (M1, 100). Anal.
Calcd for C21H23N2O5P: C, 60.87; H, 5.59; N, 6.76.
Found: C, 60.95; H, 5.60; N, 6.80.
3JHHˆ4.8 Hz, Pyr±H), 8.2 (d, 1H, JHHˆ7.9 Hz, Pyr±H),
3
3
3
7.65 (d, 2H, JHHˆ8.2 Hz, Ph±H), 7.37 (dd, 1H, JHH
ˆ
3
3
8.1 Hz, JHHˆ4.8 Hz, Pyr±H), 7.25 (d, 2H, JHHˆ8.1 Hz,
(1E,3E,5E)-3-(Diethoxyphosphoryl)-6-phenyl-1-(4-methyl-
phenyl)-2-azahexa-1,3,5-triene 10be. According to
general procedure A, imine 3b (0.5 g, 1.27 mmol), cinna-
maldehyde (0.16 mL, 1.27 mmol) and BTPP (0.38 mL,
1.24 mmol) were used. The crude residue was puri®ed by
¯ash chromatography eluting with hexane/ethyl acetate 10:1
to yield 0.2 g (40%) of 10be. According to general pro-
cedure B, imine 3b (2.32 g, 5.8 mmol), cinnamaldehyde
(0.8 mL, 6.38 mmol) and Cs2CO3 (2.4 g, 7.4 mmol) were
used. The crude residue was puri®ed by ¯ash chroma-
tography eluting with hexane/ethyl acetate 10:1 to yield
3
Ph±H), 7.11 (d, 1H, JHPˆ16.0 Hz, CHvCP), 4.15 (m,
3
4H, 2£CH2), 2.29 (s, 3H, PhCH3), 1.27 (t, 6H, JHH
ˆ
7.2 Hz, 2£CH2CH3); 13C NMR (d) 162.8 (d, JCPˆ9.0 Hz,
CvN), 155.3 (CPyr±H), 149.7 (CPyr±H), 139.6 (Carom±C),
137.8 (d, 2JCPˆ20.6 Hz, CvCP), 136.5 (CPyr±H), 135.8 (d,
1JCPˆ172.3 Hz, CvCP), 131.6±129.0 (Carom), 125.9
(Carom±C), 125.1 (CPyr±H), 62.2 (CH2), 21.3 (PhCH3),
16.2 (CH3); 31P NMR (d) 12.5; IR (NaCl, nmax) 1633
(CvN), 1350 (PvO), 1040 (P±O); EIMS m/z 359 (M1,
3). Anal. Calcd for C19H23N2O3P: C, 63.68; H, 6.47; N,
7.82. Found: C, 63.65; H, 6.50; N, 7.90.
3
1
1.3 g (60%) of 10be as a pale yellow oil; H NMR (d)
8.52 (s, 1H, CHvN), 7.20±7.75 (m, 10H, Ph±H,
3
3
(1E,3E)-3-(Diethoxyphosphoryl)-1-(2-thiophenyl)-2-aza-
penta-1,3-diene 4fa. According to general procedure A,
imine 3f (0.7 g, 1.76 mmol), acetaldehyde (0.10 mL,
1.8 mmol) and BuLi (1.6 M, 1.2 mL) were used. The
crude residue was puri®ed by ¯ash chromatography eluting
with hexane/ethyl acetate 2:1 to yield 0.37 g (70%) of 4fa as
a pale yellow oil; 1H NMR (d) 8.59 (s, 1H, CHvN), 7.45±
PhCHvCH), 6.91 (dd, 1H, JHPˆ13.8 Hz, JHHˆ11.1 Hz,
3
CHvCP), 6.81 (d, 1H, JHHˆ15.6 Hz, PhCHvCH), 4.14
(m, 4H, 2£CH2), 2.37 (s, 3H, PhCH3), 1.27 (t, 6H,
3
3JHHˆ7.0 Hz, 2£CH3); 13C NMR (d) 161.3 (d, JCPˆ
1
10.0 Hz, CvN), 142.1 (Carom±C), 136.3 (d, JCPˆ
187.6 Hz, CvCP), 133.3 (Carom±C), 131.3 (CvC±Ph),
2
129.7±127.0 (Carom), 126.4 (d, JCPˆ23.6 Hz, CvCP),
7.03 (m, 3H, TioPh±H), 6.43 (dq, 1H, JHHˆ7.0 Hz, 3JHPˆ
122.3 (d, JCPˆ16.6 Hz, CvC±Ph), 62.5 (CH2), 21.5
3
3

6328
F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
(CH3), 16.2 (CH3); 31P NMR (d) 13.0; IR (NaCl, nmax) 1590
(CvN), 1245 (PvO), 1025 (P±O); EIMS m/z 383 (M1, 31).
Anal. Calcd for C22H26NO3P: C, 68.92; H, 6.84; N, 3.65.
Found: C, 68.90; H, 6.85; N, 3.70.
6-(Diethoxyphosphoryl)-2-(4-methylphenyl)-3-phenyl-
pyridine 12a. According to general procedure, azatriene
10be (0.4 g, 1.04 mmol) was used. The crude residue was
puri®ed by ¯ash chromatography eluting with hexane/ethyl
acetate 10:1 to yield 0.2 g (50%) of 12a as a brown oil; 1H
3
3
(1E,3E,5E)-3-(Diethoxyphosphoryl)-1-(4-methylphenyl)-
2-azahepta-1,3,5-triene 10bf. According to general proce-
dure A, imine 3b (1.22 g, 3.1 mmol), crotonaldehyde
(0.25 mL, 3.1 mmol) and BTPP (0.94 mL, 3.1 mmol) were
used. The crude residue was puri®ed by ¯ash chroma-
tography eluting with hexane/ethyl acetate 15:1 to yield
0.2 g (40%) of 10bf. According to general procedure B,
imine 3b (2.9 g, 7.2 mmol), crotonaldehyde (0.6 mL,
7.9 mmol) and Cs2CO3 (3 g, 9.4 mmol) were used. The
crude residue was puri®ed by ¯ash chromatography eluting
with hexane/ethyl acetate 10:1 to yield 1.6 g (70%) of 10bf
as a pale yellow oil; 1H NMR (d) 8.47 (s, 1H, CHvN), 7.71
NMR (d) 7.85 (dd, 1H, JHHˆ7.3 Hz, JHPˆ6.5 Hz, Pyr±
3
4
H5), 7.69 (dd, 1H, JHHˆ7.3 Hz, JHPˆ6.1 Hz, Pyr±H4),
6.95±7.25 (m, 9H, Ph±H), 4.14 (m, 4H, 2£CH2), 2.37 (s,
3
3H, PhCH3), 1.27 (t, 6H, JHHˆ7.1 Hz, 2£CH3); 13C NMR
3
1
(d) 157.6 (d, JCPˆ23.1 Hz, CvN), 149.7 (d, JCPˆ
3
228.4 Hz, 6-Pyr), 139.2 (Carom±C), 138.2 (d, JCPˆ
12.6 Hz, 4-Pyr), 136.3 (Carom±C), 130.9±126.3 (Carom),
2
126.4 (d, JCPˆ25.6 Hz, 5-Pyr), 62.5 (CH2), 21.5 (PhCH3),
16.2 (CH3); 31P NMR (d) 10.8; IR (NaCl, nmax) 3050
(Carom±H), 1255 (PvO), 1023 (P±O); EIMS m/z 381
(M1, 50). Anal. Calcd for C22H24NO3P: C, 69.28; H, 6.34;
N, 3.67. Found: C, 69.40; H, 6.40; N, 3.60.
3
3
(d, 2H, JHHˆ8.1 Hz, Ph±H), 7.21 (d, 2H, JHHˆ8.05, Ph±
3
3
H), 6.74 (dd, 1H, JHPˆ18.9 Hz, JHHˆ11.0 Hz, CHvCP),
6.74 (dd, 1H, 3JHHˆ23.4 Hz, 3JHHˆ10.5 Hz, CHvCHCH3),
6.06 (m, 1H, CHvCHCH3), 4.13 (m, 4H, 2£CH2), 2.36 (s,
3H, PhCH3), 1.82 (d, 3H, 2JHHˆ6.0 Hz, CHvCHCH3), 1.30
6-(Diethoxyphosphoryl)-3-methyl-2-(4-methylphenyl)-
pyridine 12b. According to general procedure, azatriene
10bf (0.4 g, 1.24 mmol) was used. The crude residue was
puri®ed by ¯ash chromatography eluting with hexane/ethyl
acetate 5:1 to yield 0.24 g (60%) of 12b as a brown oil; 1H
3
(t, 6H, JHHˆ7.0 Hz, 2£CH3); 13C NMR (d) 160.8 (d,
3JCPˆ10.2 Hz, CvN), 141.8 (Carom±C), 136.7 (d,
NMR (d) 7.72 (dd, 1H, JHHˆ7.7 Hz, JHPˆ6.3 Hz, Pyr±
3
3
2JCPˆ23.1 Hz, CvCP), 134.4 (d, JCPˆ178.3 Hz, CvCP),
H5), 7.60 (dd, 1H, JHHˆ7.6 Hz, JHPˆ5.7 Hz, Pyr±H4),
7.38±7.17 (m, 4H, Ph±H), 4.14 (m, 4H, 2£CH2), 2.35 (s,
3H, Pyr±CH3), 2.27 (s, 3H, PhCH3), 1.27 (t, 6H,
1
3
4
133.8 (Carom±C), 131.3 (CvC±CH3), 129.7±128.5
3
(Carom), 126.0 (d, JCPˆ16.1 Hz, CvC±CH3), 62.0
(CH2), 21.5 (PhCH3), 18.8 (CvC±CH3), 16.2 (CH3); 31P
NMR (d) 14.6; IR (NaCl, nmax) 1632 (CvN), 1274
(PvO), 1029 (P±O); EIMS m/z 321 (M1, 14). Anal.
Calcd for C17H24NO3P: C, 63.54; H, 7.53; N, 4.36. Found:
C, 63.65; H, 7.60; N, 4.40.
3JHHˆ7.3 Hz, 2£CH3); 13C NMR (d) 157.6 (d, JCPˆ
3
1
23.1 Hz, CvN), 148.4 (d, JCPˆ228.6 Hz, 6-Pyr), 138.2
3
(d, JCPˆ12.6 Hz, 4-Pyr), 136.8 (Carom±CH3), 133.8
2
(Carom±CH3), 131.7±128.3 (Carom), 126.4 (d, JCPˆ
25.6 Hz, 5-Pyr), 62.8 (CH2), 21.1 (PhCH3), 20.5 (Pyr±
)
CH3), 16.2 (CH3); 31P NMR (d) 11.4; IR (NaCl, nmax
(1E,3E,5E)-3-(Diethoxyphosphoryl)-6-phenyl-1-(3-pyri-
dyl)-2-azahexa-1,3,5-triene 10eb. According to general
procedure B, imine 3e (1.06 g, 2.7 mmol), cynamaldehyde
(0.4 mL, 2.8 mmol) and Cs2CO3 (1.1 g, 3.4 mmol) were
used. The crude residue was puri®ed by ¯ash chroma-
tography eluting with hexane/ethyl acetate 5:1 to yield
3050 (Carom±H), 1261 (PvO), 1043 (P±O); EIMS m/z
319 (M1, 50). Anal. Calcd for C17H22NO3P: C, 63.94; H,
6.94; N, 4.39. Found: C, 64.05; H, 6.90; N, 4.45.
6-(Diethoxyphosphoryl)-3-phenyl-2-(3-pyridyl)pyridine
12c. According to general procedure, azatriene 10eb (0.3 g,
0.8 mmol) was used. The crude residue was puri®ed by ¯ash
chromatography eluting with hexane/ethyl acetate 5:1 to
1
0.6 g (50%) of 10be as a yellow oil; H NMR (d) 8.99 (s,
1H, Pyr±H), 8.64 (bs, 2H, Pyr±H, CHvN), 8.18 (d, 1H,
3JHHˆ8.0 Hz, Pyr±H), 7.61±7.20 (m, 7H, Ph±H, 1£Pyr±H,
CHvCHPh), 7.10±7.00 (m, 1H, CHvCHPh), 6.82 (d, 1H,
3JHPˆ15.9 Hz, CHvCP), 4.18 (m, 4H, 2£CH2), 1.27 (t, 6H,
1
yield 0.15 g (50%) of 12c as a brown oil; H NMR (d)
4
3
8.58 (d, 1H, JHHˆ2.3 Hz, Pyr±H), 8.43 (dd, 1H, JHH
ˆ
4
3
4.8 Hz, JHHˆ1.7 Hz, Pyr±H), 7.96 (dd, 1H, JHHˆ7.8 Hz,
3
3
4
3JHHˆ7.1 Hz, 2£CH3); 13C NMR (d) 158.1 (d, JCPˆ
3JHPˆ6.0 Hz, Pyr±H5), 7.78 (dd, 1H, JHHˆ7.8 Hz, JHPˆ
5.4 Hz, Pyr±H4), 7.61 (dd, 1H, 3JHHˆ7.9 Hz, 4JHHˆ1.9 Hz,
Pyr±H), 7.59±7.10 (m, 6H, 5£Ph±H, Pyr±H), 4.14 (m, 4H,
10.0 Hz, CvN), 150.3 (Pyr), 149.2 (Carom±C), 148.8
1
(Pyr), 139.1 (Carom±C), 137.1 (Pyr), 133.4 (d, JCPˆ
2
3
173.4 Hz, CvCP), 129.7±128.3 (Carom), 126.2 (d, JCPˆ
2£CH2), 1.27 (t, 6H, JHHˆ7.0 Hz, 2£CH3); 13C NMR (d)
3
3
25.1 Hz, CvCP), 124.1 (d, JCPˆ18.3 Hz, CvC±Ph),
154.4 (d, JCPˆ23.6 Hz, 2-Pyr), 152.3 (Carom±C), 150.8
1
123.1 (Carom±H), 122.3 (Pyr±H), 62.5 (CH2), 16.2
(CH3); 31P NMR (d) 13.4; IR (NaCl, nmax) 1632 (CvN),
1274 (PvO), 1029 (P±O); EIMS m/z 370 (M1, 1). Anal.
Calcd for C20H23N2O3P: C, 64.86; H, 6.26; N, 7.56. Found:
C, 64.75; H, 6.30; N, 7.50.
(Carom), 150.3 (d, JCPˆ210.1 Hz, 6-Pyr), 150.1 (Carom±
C), 137.4, 138.1, 149.4 (Carom), 135.8 (Carom±C), 129.7±
127.3 (Carom), 126.7 (d, 2JCPˆ25.6 Hz, 5-Pyr), 122.6 (Pyr),
63.2 (CH2), 16.2 (CH3),; 31P NMR (d) 10.5; IR (NaCl, nmax
)
3100 (Carom±H), 1235 (PvO), 1016 (P±O); EIMS m/z 368
(M1, 1). Anal. Calcd for C20H21N2O3P: C, 65.21; H, 5.75; N,
7.60. Found: C, 65.10; H, 5.80; N, 7.65.
Synthesis of pyridines 12
General procedure: Azatriene (10be, 10bf or 10eb) was
dissolved in 10 mL of dry toluene and the solution was
heated at re¯ux for 5 days. The solvent was removed at
reduced pressure and the crude product was puri®ed by
¯ash chromatography eluting with the appropriate solvent
to provide the pure compounds.
Acknowledgements
Â
The present work has been supported by the Direccion
General de EnsenÄanza Superior e Investigacion Cientõ®ca
(Madrid. DGESIC, PB96-0252) and by the Departamento
Â
Â

F. Palacios et al. / Tetrahedron 56 (2000) 6319±6330
6329
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Â
de Educacion, Universidades e Investigacion del Gobierno
Vasco (Vitoria, PI98-53). M. Rodriguez thanks the
Â
Â
Direccion General de EnsenÄanza Superior e Investigacion
Cientõ®ca (Madrid) for a predoctoral fellowship.
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