Aza-Wittig reaction of N-vinylic phosphazenes with carbonyl compounds. Azadiene-mediated synthesis of isoquinolines and 5,6-dihydro-2H-1,3-oxazines

Article abstract of DOI:10.1021/jo961664n

N-Vinylic phosphazenes 4 are obtained by reaction of phosphorus ylide 5 and nitriles 6. Ala-Wittig reaction of phosphazenes 4 with aldehydes leads to the formation of 2-azadienes 1, which are easily converted into isoquinolines 2. Reaction of conjugated phosphazenes 4 with ethyl glyoxalate affords 5,6-dihydro-2H-1,3-oxazines 9 in a regio- and stereoselective fashion, while heterodienes 1 react with ethyl glyoxalate and diethyl ketomalonate giving 1,3-oxazines 11 and 12.

Full text of DOI:10.1021/jo961664n

1146
J . Org. Chem. 1997, 62, 1146-1154
Aza -Wittig Rea ction of N-Vin ylic P h osp h a zen es w ith Ca r bon yl
Com p ou n d s. Aza d ien e-Med ia ted Syn th esis of Isoqu in olin es a n d
5,6-Dih yd r o-2H-1,3-oxa zin es
Francisco Palacios,* Concepcio´n Alonso, and Gloria Rubiales
Departamento de Quı´mica Orga´nica, Facultad de Farmacia, Universidad del Pais Vasco,
Apartado 450, 01080 Vitoria, Spain
Received August 29, 1996X
N-Vinylic phosphazenes 4 are obtained by reaction of phosphorus ylide 5 and nitriles 6. Aza-
Wittig reaction of phosphazenes 4 with aldehydes leads to the formation of 2-azadienes 1, which
are easily converted into isoquinolines 2. Reaction of conjugated phosphazenes 4 with ethyl
glyoxalate affords 5,6-dihydro-2H-1,3-oxazines 9 in a regio- and stereoselective fashion, while
heterodienes 1 react with ethyl glyoxalate and diethyl ketomalonate giving 1,3-oxazines 11 and
12.
In tr od u ction
the preparation of biologically active natural products9a
and the construction of the framework of pharmacologi-
cally active alkaloids.9b,c
Azadienes have been widely used as synthons in the
building of nitrogen six-membered rings in a highly regio-
and stereospecific way by using hetero-Diels-Alder
processes, and in the last decade some new methods of
generating 2-azadienes have been found that have in-
creased the scope of this approach.1 Likewise, phosp-
hazenes2 represent an important class of compounds and
have attracted a great deal of attention in recent years
because of their broad range of applications, showing that
the use of phosphazenes represent an effective strategy
for the construction of carbon-nitrogen double bonds.3
Furthermore, the utility of N-vinylic phosphazenes4 has
been recently demonstrated in the synthesis of function-
alized imine compounds such as 2-azadienes5 and as key
intermediates in the preparation of heterocycles such as
pyridine derivatives,5a,d,6 polycyclic compounds,4,7 and
benzodiazepines8 as well as in elegant routes toward both
Elsewhere, we have used the aza-Wittig reaction of
N-vinylic phosphazenes with carbonyl compounds, lead-
ing to a very efficient method for the preparation of
2-azadienes substituted with a phosphine oxide group in
the 4-position5d and derived from R-5b,c and â-amino
acids.5a Following on from our previous studies on the
reactivity and the synthetic utility of phosphazenes2 and
azadienes,5 here we aim to explore a new and effective
strategy for the preparation of electronically neutral
2-azadienes 1 as well as their synthetic utility in the
preparation of isoquinolines 2 and 5,6-dihydro-2H-1,3-
oxazines 3. Retrosynthetically, we envisaged the prepa-
ration of azadienes 1 by aza-Wittig reaction of N-vinylic
phosphazenes 4, obtained from the reaction between
phosphorus ylide 5 and nitriles 6; electrocyclic ring
closure of azadienes 1 (R1 ) C6H5) provided isoquinolines
2, while hetero-Diels-Alder reaction of azadienes 1 with
carbonyl compounds led to the formation of oxazines 3
(Scheme 1).
* To whom correspondence should be addressed. Tel.: 34-45-183103.
Fax: 34-45-130756. E-mail: qoppagaf@vf.ehu.es.
X Abstract published in Advance ACS Abstracts, J anuary 1, 1997.
(1) (a) For reviews, see: (a) Boger, D. L. In Comprehensive Organic
Synthesis; Trost, B. M., Paquette, L. A., Eds.; Pergamon Press: Oxford,
1991; Vol. 5, pp 451. (b) Barluenga, J .; J oglar, J .; Gonzalez, F. J .;
Fustero, S. Synlett 1990, 129. (c) Fringuelli, F.; Tatichi, A. In Dienes
in the Diels-Alder Reaction; Willey: New York, 1990. (d) Boger, D.
L.; Weinreb, S. M. In Hetero Diels-Alder Methodology in Organic
Chemistry; Academic Press: San Diego, 1987; p 239. (e) Ghosez, L.;
Serckx-Poncin, B.; Rivero, M.; Bayard, Ph.; Sainte, F.; Dermoulin, A.;
Frisque-Hesbain, A. M.; Mockel, A.; Mun˜oz, L.; Bernard-Henriet, C.
Lect. Heterocycl. Chem. 1985, 8, 69. (f) Barluenga, J .; Toma´s, M.
Adv. Heterocycl. Chem. 1993, 57, 1. (g) Ghosez, L.; Bayard, Ph.;
Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.;
Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995,
51, 11021.
Resu lts a n d Discu ssion
The synthesis of conjugated phosphazenes 4 was
accomplished very easily, with a high yield, by the
reaction of commercially available aryl and heterocyclic
nitriles 6 and phosphorus ylide 5 in benzene. This
strategy had been previously used in the preparation of
functionalized phosphazenes by reaction of phosphorus
ylides10 and simple phosphazenes11 with aryl nitriles.
Crystalline compounds 4 were characterized on the basis
of their spectroscopic data. Thus, the 31P NMR spectrum
for 4a showed an absorption at δP 2.51 ppm, and in the
(2) For a review see: Barluenga, J .; Palacios F. Org. Prep. Proc. Int.
1991, 23, 1.
(3) For recent reviews of the aza-Wittig reaction see: (a) Molina,
P.; Vilaplana, M. J . Synthesis 1994, 1197. (b) Eguchi, S; Matsushita,
Y.; Yamashita, K. Org. Prep. Proc. Int. 1992, 24, 209. (c) Gulolubov,
Y. G.; Kaskhin, L. F. Tetrahedron 1992, 48, 1353.
(4) For a review see: Nitta, M. In Reviews on Heteroatom Chemistry;
Oae, S., Ed.; MYU: Tokyo, 1993; Vol. 9, p 87.
(5) (a) Palacios, F.; Pe´rez de Heredia, I.; Rubiales, G. J . Org. Chem.
1995, 60, 2384. (b) Barluenga, J .; Ferrero, M.; Palacios, F. Tetrahedron
Lett. 1990, 31, 3497. (c) Barluenga, J .; Ferrero, M.; Palacios, F.
Tetrahedron Lett. 1988, 29, 4863. (d) Palacios, F.; Aparicio, D.; de los
Santos, J . M. Tetrahedron 1996, 52, 4857.
(6) (a) Katritzky, A. R.; Mazurkiewicz, R.; Stevens, C. V.; Gordeev,
M. F. J . Org. Chem. 1994, 59, 2740. (b) Molina, P.; Pastor, A.;
Vilaplana, M. J . Tetrahedron Lett. 1993, 34, 3773. (c) Molina, P.; Pastor,
A.; Vilaplana, M. J . Tetrahedron 1993, 49, 7769. (d) Oikawa, T.;
Kanomata, N.; Toda, M. J . J . Org. Chem. 1993, 58, 2046. (e) Kru-
tosikova, A.; Dandarova, M.; Chylova, J .; Vegh, D. Monatsh Chem.
1992, 123, 807.
(7) Nitta, M.; Iino, Y.; Mori, S.; Takayasu, T. J . Chem. Soc., Perkin
Trans. 1 1995, 1001.
(8) Kurita, J .; Iwata, T.; Yasnike, S.; Tsuchita, T. Chem. Commun.
1992, 81.
(9) (a) Molina, P.; Fresnada, P. M.; Garc´ıa-Zafra, S. Tetrahedron Lett.
1995, 36, 3581 and references cited therein. (b) Molina, P.; Fresnada,
P. M.; Garc´ıa-Zafra, S. Synlett 1995, 43. (c) Chavignon, D.; Teulade,
J . C.; Roche, D.; Madesclaire, H.; Blanche, Y.; Gueiffier, A.; Chabard,
J . L.; Dauphin, G. J . Org. Chem. 1994, 59, 6413.
(10) (a) Ciganek, E. J . Org. Chem. 1970, 35, 3631. (b) Saito, T.;
Nakane, M.; Endo, M.; Yamashita, H.; Oyameda, Y.; Motoki, S. Chem.
Lett. 1986, 135. (c) Capucino, L.; Brauni, C.; Ku¨hn, F. Liebigs Ann.
Chem. 1992, 15.
(11) Barluenga, J .; Ferrero, M.; Lopez, F.; Palacios, F. J . Chem Soc.,
Perkin Trans. 1 1989, 615.
S0022-3263(96)01664-7 CCC: $14.00 © 1997 American Chemical Society

Reaction of N-Vinylic Phosphazenes with CO Compounds
J . Org. Chem., Vol. 62, No. 4, 1997 1147
Sch em e 1. Gen er a l Str a tegy for F or m a tion a n d
Syn th etic Use of 2-Aza d ien es
absorption at δ 8.50 ppm also as a singlet. NOE
difference experiments were combined with the informa-
tion derived from the 1H NMR spectra to confirm the
stereochemistry of azadienes 1a a -1a c. At room tem-
perature in CDCl3 the selective saturation of the singlet
at 8.50 ppm of compound 1a b afforded positive NOE over
the furan proton and an absence of interaction with the
olefinic proton (Figure 1). Therefore, this NOE observa-
tion was consistent with the E configuration around the
carbon-nitrogen double bond (CdN), with a Z configu-
ration around the carbon-carbon double bond (CdC) of
azadiene 1a b and supports an s-trans conformation for
the azadiene backbone.1g Different behavior was ob-
served, however, when phosphazenes 4b-d reacted with
aldehydes leading to the formation of azadienes 1 ob-
tained as a mixture of E,Z- and Z,Z-isomers (Table 1,
entries 4-16).
Sch em e 2. Aza d ien e 1 F or m a tion th r ou gh
Aza -Wittig Rea ction
In order to test the synthetic usefulness of the new
azadienes 1 as key intermediates in organic synthesis
and especially in the preparation of new nitrogen-
containing heterocycles, the electrocyclic ring closure of
azadienes 1 was explored. Thus, heating azadienes 1,
not only the E,Z-isomers but also mixtures of Z,Z- and
E,Z- isomers, in refluxing xylene afforded isoquinolines
2 in very high yields (Table 1, entries 17-20). The
formation of heterocycles 2 (Scheme 3) could be explained
via 1,6-electrocyclic ring-closure of azadienes 1 followed
by dehydrogenation under the reaction conditions of the
nonisolable annelated compound 8. Several examples of
synthesis of heterocyclic compounds by means of tandem
aza-Wittig/electrocyclic ring-closure of conjugated phos-
phazenes containing an ethoxycarbonyl group have been
reported in recent years,3a and this strategy has even
been successfully utilized in the synthesis of â-carboline13a
and azafluoranthene alkaloids.13b However, in our case
the mild reaction conditions used allowed us to stop the
aza-Wittig reaction of phosphazenes and aldehydes in the
formation of electronically neutral azadienes 1. On the
other hand, from a preparative point of view, it is
noteworthy that isoquinolines 2 can alternatively be
obtained in a “one-pot” procedure, when phosphazenes 1
are directly heated in refluxing xylene with aldehydes.
Sch em e 3. P h osp h a zen es 4 F or m a tion th r ou gh
Rea ction of P h osp h or a n e 5 a n d Nitr iles 6
Aza-Wittig reaction of phosphazenes 4 and aldehydes
was extended, and the reaction with ethyl glyoxalate was
also explored. Surprisingly, when ethyl glyoxalate was
added to compounds 4 at room temperature, formation
of the expected azadienes 10 was not observed, and the
six-membered heterocycle 9 was isolated instead (Scheme
4, Table 2, entries 1-3) in a regio- and stereoselective
fashion. 1,3-Oxazines 9 proved to be single stereoisomers
and were characterized on the basis of their spectroscopic
data and mass spectrometry. For instance, mass spec-
trometry of 9a showed the molecular ion peak (m/ z 371,
5). Vicinal H-5 and H-6 coupling constants of compounds
9 in the range of 3.0-3.5 Hz suggested that both proton
atoms were relatively cis,14 while the absence of coupling
between H-5 and H-2 could support the trans configura-
tion of these protons. NOE difference experiments were
used to confirm the stucture of compound 9c. At room
temperature in CDCl3, the selective saturation at 5.36 δ
(H-6) afforded significant NOE (13%) over the adjacent
1H NMR spectrum of 4a the vinylic proton resonated at
δH 6.15 ppm as a well-resolved doublet with the long-
4
range coupling constant of J PH ) 3.7 Hz, while in the
13C NMR spectrum of 4a the olefinic carbon in â position
to the nitrogen atom gave a doublet at δC 111.0 ppm with
3
a coupling constant of J PC ) 19 Hz. Formation of
conjugated phosphazenes 4 can be explained through [2
+ 2] cycloaddition10a,11,12 followed by ring opening of the
unstable cyclic pentavalent phosphorus compounds 7
(Scheme 2).
Aza-Wittig reaction of N-vinylic phosphazene 4a con-
taining a 2-furyl group as the substituent in the 3
position, with heteroaromatic and aromatic aldehydes in
refluxing CHCl3, gave high yields of electronically neutral
azadienes 1a a -1a c (Scheme 3, Table 1, entries 1-3).
These compounds 1 were characterized on the basis of
their spectroscopic data and mass spectrometry, which
indicated that only the E,Z-isomers were obtained. For
instance, the olefinic proton of 1a b gave 1H resonance
at δ 6.63 ppm as a singlet, while the iminic proton showed
(13) (a) Molina, P.; Murcia, F.; Fresneda, P. M. Tetrahedron Lett.
1994, 35, 1453 and references cited therein. (b) Molina, P.; Garc´ıa-
Zafra, S.; Fresneda, P. M. Synlett 1995, 43.
(12) Barluenga, J .; Lopez, F.; Palacios, F.; Sanchez-Ferrando, F.
Tetrahedron Lett. 1988, 29, 381.
(14) Breitmeier, E. In Structures Elucidation by NMR in Organic
Chemistry. A Practical Guide; Wiley: London, 1993; p 23.

1148 J . Org. Chem., Vol. 62, No. 4, 1997
Palacios et al.
Ta ble 1. 2-Aza d ien es 1 a n d Isoqu in olin es 2 Obta in ed
reaction condns
T (°C) time (h)
80 15
starting
material
entry
products
R2
R3
phenyl
yielda (%)
E/Z ratiob
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
4a
4a
4a
4b
4b
4b
4b
4c
4c
4c
4c
4c
1a a
1a b
1a c
1ba
1bb
1bc
1bd
1ca
1cb
1cc
1cd
1ce
1cf
1d a
1d b
1d c
2a
2-furyl
83
95
65
80
98
60
70
95
70
60
90
77
62
81
99
90
100/0
100/0
100/0
50/50
100/0
50/50
40/60
40/60
50/50
40/60
40/60
50/50
40/60
80/20
50/50
40/60
2-furyl
2-furyl
3-pyridyl
2-pyrrolyl
phenyl
3-pyridyl
3-indolyl
2-thienyl
phenyl
80
80
80
80
80
17
136
15
17
192
40
2-thienyl
2-thienyl
2-thienyl
2-thienyl
phenyl
80
80
24
phenyl
phenyl
phenyl
phenyl
3-pyridyl
5-Me-2-furyl
2-thienyl
2-pyrrolyl
3-indolyl
phenyl
3-pyridyl
5-Me-2-furyl
phenyl
80
80
80
80
80
80
80
80
140
140
140
140
15
144
14
192
136
63
15
66
12
15
4c
phenyl
4d
4d
4d
1a a
1bb
1cb
1d a
3-pyridyl
3-pyridyl
3-pyridyl
2-furyl
2-thienyl
phenyl
83 (94)c
70
82
78
2b
2c
2d
3-pyridyl
3-pyridyl
phenyl
15
17
3-pyridyl
a
b
Purified by flash chromatography. E/Z ratio by GC and 1H-NMR assignment. c Yield of product 2a in “one-pot” reaction from 4a
and benzaldehyde.
this behavior may be consistent with our previous result
obtained for 2-azadienes derived from â-amino acids5a as
well as in intramolecular Diels-Alder cyclization pro-
cesses.17 Hetero-Diels-Alder reactions represent a great
potential for the efficient construction of heterocycles,18
natural products,19a,b and asymmetric synthesis.19b-e In
our case, the reaction of phosphazenes 4 with ethyl
glyoxalate led to a new approach to the formation of 5,6-
dihydro-2H-1,3-oxazines 9 with controlled stereochem-
F igu r e 1.
istry of three stereocenters. In this context, it is note-
wortly that 2H-1,3-oxazines are excellent synthetic
intermediates in organic synthesis.20
Sch em e 4. 2H-1,3-Oxa zin es 9 F or m a tion th r ou gh
Rea ction of P h osp h a zen es 4 a n d Eth yl Glyoxa la te
In order to test whether azadienes 10 are intermedi-
ates in this process, we tried to stop the reaction at the
first step, i.e., in the azadienes 10, but the isolation of
compounds 10 was cumbersome to carry out on a routine
basis. However, the presence of the azadiene 10a in the
1
crude reaction mixture was detected by H NMR21 when
phosphazene 4a was treated with ethyl glyoxalate at 0
°C. The addition of a second equivalent of aldehyde to
the reaction mixture used “in situ” without isolation of
the azadiene 10a gave 1,3-oxazine 9a .
To enhance and generalize the synthetic use of aza-
dienes 1 obtained through aza-Wittig reaction of phosp-
hazenes and aldehydes (Scheme 3) as well as the prepa-
ration of 1,3-oxazines, the reaction of heterodienes 1 with
ethyl glyoxalate was studied. Thus, cycloaddition of (Z,Z)
azadienes 1 with ethyl glyoxalate was attempted at 120
°C using toluene as solvent, but no reaction took place.
proton (H-5) and low positive NOE (3%) over the proton
at C-2, while an appreciable integral enhancement was
seen between the proton at C-2 and one of the aryl
protons of the C-5 phenyl group (Figure 2). Both
observations were compatible with structure 9, in which
three new stereogenic centers are created.
Formation of azadienes 9 can be explained by aza-
Wittig reaction of phosphazenes 4 and the aldehyde to
give azadienes 10 followed by [4 + 2] cycloaddition
reaction of heterodiene 10 with a second molecule of ethyl
glyoxalate (Scheme 4). Interestingly, heterocycles 9 were
obtained as single stereoisomers and therefore suggested
that the reaction of azadienes 10 with ethyl glyoxalate
underwent exo selectivity (Figure 2). Although [4 + 2]
cycloaddition processes of electronically neutral 2-aza-
dienes with endo selectivity have also been reported,15,16
(16) Cheng, Y. S.; Ho, E.; Mariano, P. S.; Amman, H. L. J . Org.
Chem. 1985, 50, 5678.
(17) Ho, E.; Cheng, Y. S.; Mariano, P. S. Tetrahedron Lett. 1988,
29, 4799.
(18) For a review see: Waldmann, H. Synlett 1995, 133.
(19) For recent contributions of hetero-Diels-Alder reaction see: (a)
Kaufman, M. D.; Grieco, P. A. J . Org. Chem. 1994, 59, 7197. (b) Mulzer,
J .; Meyer, F.; Buchmann, J .; Luger, P. Tetrahedron Lett. 1995, 36, 3503.
(c) Mikami, K.; Motoyama, Y.; Terada, M. J . Am. Chem. Soc. 1994,
116, 2812. (d) J ohannsen, M.; J orgensen, K. A. J . Org. Chem. 1995,
60, 5757. (e) Mikami, K.; Kotero, O.; Motoyama, Y.; Sakaguchi, H.
Synlett 1995, 975.
(20) For recent contributions see: (a) Cherkauskas, J . P.; Klos, A.
M.; Borzilleri, R. M.; Sisko, J .; Weinreb, S. M. Tetrahedron 1996, 52,
3135. (b) Barluenga, J .; Tomas, M.; Ballesteros, A.; Kong, J . S.
Tetrahedron 1996, 52, 3095.
(15) Barluenga, J .; J oglar, J .; Fustero, S.; Gotor, V.; Kru¨ger, C.;
Romao, M. J . Chem. Ber. 1985, 118, 3652.
(21) The reaction was monitored by 31P and 1H NMR showing the
disappearance of phosphazene 4 and the formation of azadiene 10.

Reaction of N-Vinylic Phosphazenes with CO Compounds
J . Org. Chem., Vol. 62, No. 4, 1997 1149
Ta ble 2. Com p ou n d s 9, 11, 12, a n d 12′ Obta in ed
reaction condns
T (°C) time (h)
entry
starting material
products
R2
R3
yielda (%)
12/12′ ratiob
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
4a
4b
4c
9a
9b
9c
2-furyl
2-thienyl
phenyl
2-furyl
2-thienyl
phenyl
2-furyl
2-furyl
2-furyl
2-thienyl
2-thienyl
phenyl
phenyl
phenyl
phenyl
3-pyridyl
3-pyridyl
rt
rt
rt
12
48
72
60
80
68
1a b
1bb
1cb
1a a
1a b
1a c
1ba
1bb
1cb
1cc
1cd
1cf
1d b
1d c
11a
11b
11c
12a
12b
12c
12d
12e
12f
12g
12h
12i
12j
12k
3-pyridyl
3-pyridyl
3-pyridyl
phenyl
3-pyridyl
2-pyrrolyl
phenyl
3-pyridyl
3-pyridyl
5-Me-2-furyl
2-thienyl
3-indolyl
3-pyridyl
5-Me-2-furyl
80/rtc
80/rtc
80/rtc
rtc
144/20c
76/78c
65/70c
63/65c
78
144/14c
144/18c
4
1
1
2
2
100/0
100/0
100/0
70/30
70/30
100/0
70/30
70/30
100/0
100/0
70/30
rtc
62
58
78
43
80
68
88
63
rtc
rtc
rtc
rtc
4
rtc
17
96
48
96
72
rtc
rtc
rtc
66
55
rtc
a
b
Purified by flash chromatography. 12/12′ ratio by GC and 1H-NMR assignment. c Reaction was performed in the presence of LP-
Et2O.
F igu r e 3.
F igu r e 2.
of compounds 9. This process occurred with high ste-
reospecificity and can be regarded as a two-step cycload-
dition through zwitterionic species 13 (Figure 3); subse-
quent cyclization can afford oxazines 11 containing the
2,6-cis-configuration, which is more stable than the trans
one. In this context, it is noteworthy that zwitterionic
intermediates have been proposed as participants in
Lewis acid-catalyzed Diels-Alder processes,1c,22 while, to
the best of our knowledge, these types of intermediates
are less frequent in this kind of cycloaddition carried out
in the absence of a catalyst. From a preparative point
of view, it is noteworty that 1,3-oxazines 11 can also be
obtained when a mixture of (Z,Z)- and (E,Z)-azadienes 1
is directly heated in CHCl3 with ethyl glyoxalate.
Diethyl ketomalonate also reacted with azadienes 1.
However, in this case the presence of LP-Et2O as a
catalyst was required23 and afforded a mixture of cy-
cloadducts 12 and 12′ (Scheme 5), with a higher propor-
tion of cis isomer 12 than the trans isomer 12′ (Table 3,
entries 7-17). Formation of 1,3-oxazines 12/12′ can also
be explained through a two-step cycloaddition process,
although now the presence of two substituents in position
6 of compounds 12/12′ as opposed to the presence of only
one substituent in heterocycles 11 could explain the
formation of both isomers 12 and 12′, but with a higher
proportion of the more stable 12.
Sch em e 5. Rea ction of Aza d ien es 1 w ith Eth yl
Glyoxa la te a n d Dieth yl Ketom a lon a te
However, 2H-1,3-oxazines 11 (Scheme 5) were obtained
as single isomers when (E,Z)-heterodienes 1 reacted with
ethyl glyoxalate in refluxing CHCl3 (Table 2, entries
4-6). Even higher yields were obtained when this
reaction was performed in the presence of lithium per-
chlorate in a nonaqueous solvent such as diethyl ether
(LP-Et2O) in a similar way as in processes previously
reported.5a In contrast to 1,3-oxazines 9, heterocycle 11
seemed to show a different configuration at C-2, given
that the long-range coupling constant (5J H ) for com-
2H5
We conclude that N-vinylic phosphazenes 4, easily
obtained by reaction of phosphorane 5 and nitriles 6, can
be intermediates in the preparation of azadienes 1,
isoquinolines 2, and 5,6-dihydro-2H-1,3-oxazines 9, in
pounds 11 appeared in the range of 2.0-2.5 Hz, and these
results could be consistent with the cis-configuration
between both protons (H-2 and H-5). 1H NMR NOE
experiments confirmed the structure of 1,3-oxazines 11
because a significant integral enhancement was seen
between the proton at C-6 and both protons at C-2 and
C-5 (Figure 3). Formation of heterocycles 11 can be
assumed in terms of a formal [4 + 2] cycloaddition but
in a different pathway to that observed in the formation
(22) (a) Sauer, J .; Sustmann, R. Angew. Chem., Int. Ed. Engl. 1980,
19, 779. (b) Larson, E. R.; Danishefsky, S. J . Am. Chem. Soc. 1982,
104, 6458.
(23) Cycloaddition of azadienes 4 with diethyl ketomalonate was
attempted at 120 °C using toluene as solvent, but no reaction took
place and starting materials were recovered.

1150 J . Org. Chem., Vol. 62, No. 4, 1997
Palacios et al.
0.520 g (5 mmol) of 3-cyanopyridine, and the mixture was
stirred at reflux for 48 h. The crude product was chromato-
graphed on neutral aluminum oxide (AcOEt) to give 1.938 g
(85%) of a yellow oil that was dissolved in AcOEt, and the
solution deposited yellow crystals (1.892 g, 83%) of 4d : mp
which three chiral centers are created. Electronically
neutral 2-azadienes 1 are suitable 4π systems in [4 + 2]
cycloaddition reactions with ethyl glyoxalate and diethyl
ketomalonate to yield 1,3-oxazines 11 and 12. The
striking difference between the structure of oxazines 9
and that of 11, both containing three new stereogenic
centers, may be described as a symmetry-allowed one-
step mechanism in the first case and a two-step mech-
anism involving a zwitterionic intermediate in the sec-
ond. It is worth noting that 2H-1,3-oxazines are poten-
tially useful synthons for stereoselective construction of
acyclic derivatives.20
4
134-135 °C; 1H NMR (CDCl3, 300 MHz) δ 8.34 (d, J HH ) 1.4
Hz, 1H), 8.14-8.07 (m, 3H), 7.65-7.07 (m, 19H), 6.64-6.59
(m, 1H), 5.69 (d, 4J PH ) 3.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz)
δ 148.5 (s),147.1 (s), 139.6 (s), 134.8 (s), 132.7-128.0 (m), 123.4
(d, 1J PC ) 141.5 Hz), 113.5 (d,3J PC ) 19 Hz); 31P NMR (CDCl3,
120 MHz) δ 0.49; IR (KBr) 1394; MS (EI) m/ z 456 (M+, 81).
Anal. Calcd for C31H25N2P: C, 81.55; H, 5.52; N, 6.14.
Found: C, 81.52; H, 5.51; N, 6.15.
Gen er a l P r oced u r e for th e P r ep a r a tion of 2-Aza d ien es
1. Aldehyde (5 mmol) was added to a 0-10 °C solution of
phosphazene 4 (5 mmol) in CHCl3 (15 mL) under N2, and the
mixture was refluxed until TLC indicated the disappearance
of phosphazene. Evaporation of solvent under reduced pres-
sure afforded an oil that was chromatographed on neutral
aluminum oxide to give the 2-azadienes 1.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined with
a Bu¨chi SPM-20 apparatus and are uncorrected. Elemental
analyses were performed in a LECO CHNS-932 apparatus.
IR spectra were obtained as neat oils or solids in KBr on a
Nicolet IRFT Magna 550 spectrometer. 1H (250 MHz), and
13C (75 MHz), 31P (120 MHz) spectra and NOE experiments
were recorded on a Variant VXR 300 MHz spectrometer in
(1E,3Z)-1,4-Dip h en yl-3-(2-fu r yl)-2-a za b u t a -1,3-d ien e
(1a a ). The general procedure was followed using benzalde-
hyde (0.505 mL, 5 mmol) and 2.225 g (5 mmol) of phosphazene
4a (15 h). The crude oil was chromatographed on neutral
aluminum oxide (Et2O/hexane1/3) to give 1.133 g (83%) of 1a a
as a yellow oil (Rf ) 0.53): 1H NMR (300 MHz, CDCl3) δ 8.47
(s, 1H), 7.94-7.05 (m, 11H), 6.59 (s, 1H), 6.42 (m, 1H), 6.28
1
CDCl3 solution with TMS as internal reference for H and 13C
NMR spectra and phosphoric acid (85%) for 31P NMR spectra.
Mass spectra were obtained on
a Hewlett-Packard 5971
3
spectrometer (70 eV). TLC’s were developed on Kieselgel 60
F254 sheets (Merck); column chromatography was performed
on silica gel 60 and on aluminum oxide 90 active, neutral
(0.063-0.200 mm). Benzene, xylene, and diethyl ether were
distilled from benzophenone ketyl and sodium, while chloro-
form was distilled from P2O5. Standard experimental param-
eters for the acquisition of NOE difference spectra were used.
Phosphazene 4c was prepared as described in the literature.10a
Additional spectral data (13C NMR, IR, and MS) for compounds
1a a -1d c and 12a -12k are given in the Supporting Informa-
tion.
(d, J HH ) 3.3 Hz, 1H). Anal. Calcd for C19H15NO: C, 83.48;
H, 5,54; N, 5.13. Found: C, 83.16 H, 5.56; N, 5.12.
(1E,3Z)-3-(2-F u r yl)-4-p h en yl-1-(3-p yr id yl)-2-a za b u t a -
1,3-d ien e (1a b). The general procedure was followed using
3-pyridinecarboxaldehyde (0.472 mL, 5 mmol) and 2.225 g (5
mmol) of phosphazene 4a (17 h). The crude oil was chromato-
graphed on neutral aluminum oxide (Et2O/hexane 1/1) to give
1.301 g (95%) of 1a b as a yellow oil (Rf ) 0.28): 1H NMR (300
4
3
MHz, CDCl3) δ 9.02 (d, J HH ) 1.9 Hz, 1H), 8.74 (dd, J HH
)
4
4.8 Hz, J HH ) 1.9 Hz, 1H), 8.50 (s, 1H), 8.3 (m, 1H), 7.60-
3
3
7.17 (m, 8H), 6.63 (s, 1H), 6.44 (dd, J HH ) 1.8 Hz, J HH ) 3.3
3
Gen er a l P r oced u r e for th e P r ep a r a tion of N-Vin ylic
P h osp h a zen es 4. A solution in benzene (10 mL) and 3.125
mL of 1.6 M solution of methyllithium in ether (5 mmol) was
added dropwise to a solution of 2.400 g (5 mmol) of benzyl-
triphenylphosphonium iodide in benzene (20 mL) cooled to 0
°C under N2.The clear red solution was heated to reflux for 1
h. A solutionof nitrile 6 (5 mmol) in benzene (5 mL) was added
dropwise and stirred as was shown for 4a -d . The mixture
was cooled at rt, filtered, and concentrated to afford an oil.
1,1,1,4-Tetr a p h en yl-3-(2-fu r yl)-2-a za -1λ5-p h osp h a bu ta -
1,3-d ien e (4a ). The general procedure was followed using
0.437 mL (5 mmol) of 2-furonitrile, and the mixture was stirred
at rt for 96 h. The crude product was chromatographed on
neutral aluminum oxide (AcOEt) to give 1.446 g (65%) of a
yellow oil that was dissolved in AcOEt, and the solution
deposited yellow crystals (1.335 g, 60%) of 4a : mp 131-132
°C; 1H NMR (CDCl3, 300 MHz) δ 7.98-6.78 (m, 21H), 6.15 (d,
4J PH ) 3.7 Hz, 1H), 6.04 (m, 2H); 13C NMR (CDCl3, 75 MHz)
δ 158.7 (s), 139.8 (s), 139.5 (s), 137.3 (s), 133.0-124.1 (m), 111.0
Hz, 1H), 6.30 (d, J HH ) 3.3 Hz). Anal. Calcd for C18H14N2O:
C, 78.80; H, 5.15; N, 10.22. Found: C, 78.82; H, 5.13; N, 10.20.
(1E,3Z)-3-(2-F u r yl)-4-p h en yl-1-(2-p yr r olyl)-2-a za bu ta -
1,3-d ien e (1a c). The general procedure was followed using
2-pyrrolecarboxaldehyde (0.475 g, 5 mmol) and 2.225 g (5
mmol) of phosphazene 4a (136 h). The crude oil was chro-
matographed on neutral aluminum oxide (Et2O/hexane 1/1)
to give 0.851 g (65%) of 1a c as a yellow oil (Rf ) 0.60): 1H
NMR (300 MHz, CDCl3) δ 10.04 (s, 1 H), 8.14 (s, 1H), 7.88-
6.85 (m, 7H), 6.54 (m, 1H), 6.51 (s, 1H), 6.32 (m, 1H), 6.2 (m,
2H). Anal. Calcd for C17H14N2O: C, 77.83; H, 5.38; N, 10.69.
Found: C, 77.81; H, 5.39; N, 10.65.
(3Z)-1,4-Dip h e n yl-3-(2-t h ie n yl)-2-a za b u t a -1,3-d ie n e
(1ba ). The general procedure was followed using benzalde-
hyde (0.505 mL, 5 mmol) and 2.305 g (5 mmol) of phosphazene
4b (15 h). The crude oil was chromatographed on neutral
aluminum oxide (Et2O/hexane 1/1) to give 1.156 g (80%) of a
50:50 diastereomeric mixture of E/Z isomers of 1ba as a yellow
oil (Rf ) 0.62): 1H NMR (300 MHz, CDCl3) δ 8.52 (s, 1H) for
the E-isomer, 8.30 (s, 1H) for the Z-isomer, 8.00-7.06 (m, 21
H), 7.02 (s, 1H) for the Z-isomer, 6.55 (s, 1H) for the E-isomer.
Anal. Calcd for C19H15NS: C, 78.86; H, 5.23; N, 4.84. Found:
C, 78.89; H, 5.22; N, 4.86.
3
(d, J PC ) 19 Hz), 110.7 (s), 105.8 (s); 31P NMR (CDCl3, 120
MHz) δ 2.51; IR (KBr) 1446, 1123; MS (EI) m/ z 445 (M+, 38).
Anal. Calcd for C30H24NOP: C, 80.87; H, 5.43; N, 3.15.
Found: C, 80.72; H, 5.40; N, 3.16.
1,1,1,4-Tetr aph en yl-3-(2-th ien yl)-2-aza-1λ5-ph osph abu ta-
1,3-d ien e (4b). The general procedure was followed using
0.466 mL (5 mmol) of 2-thiophenecarbonitrile, and the mixture
was stirred at rt for 72 h. The crude product was chromato-
graphed on neutral aluminum oxide (AcOEt) to give 1.498 g
(65%) of a yellow oil that was dissolved in AcOEt, and the
solution deposited yellow crystals (1.383 g, 60%) of 4b: mp
118-119 °C; 1H NMR (CDCl3, 300 MHz) δ 7.92-6.48 (m, 23H),
6.02 (d, 4J PH ) 2.2 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ 141.1
(1E,3Z)-4-P h en yl-1-(3-p yr id yl)-3-(2-th ien yl)-2-a za bu ta -
1,3-d ien e (1bb). The general procedure was followed using
3-pyridinecarboxaldehyde (0.472 mL, 5 mmol) and 2.305 g (5
mmol) of phosphazene 4b (17 h). The crude oil was chromato-
graphed on neutral aluminum oxide (Et2O/hexane 1/1) to give
1.421 g (98%) of 1bb as a yellow oil (Rf ) 0.28): 1H NMR (300
4
3
MHz, CDCl3) δ 8.99 (d, J HH ) 1.8 Hz, 1H), 8.72 (dd, J HH
)
4
4.8 Hz, J HH ) 1.8 Hz, 1H), 8.49 (s, 1H), 8.31-8.28 (m, 2 H),
7.80-7.00 (m, 8H), 6.53 (s, 1H). Anal. Calcd for C18H14N2S:
C, 74.46; H, 4.86; N, 9.65. Found: C, 74.50; H, 4.85; N, 9.68.
(3Z)-1-(3-In d olyl)-4-p h en yl-3-(2-th ien yl)-2-a za bu ta -1,3-
d ien e (1bc). The general procedure was followed using
3-indolecarboxaldehyde (0.726 g, 5 mmol) and 2.305 g (5 mmol)
of phosphazene 4b (192 h). The crude oil was chromato-
graphed on neutral aluminum oxide (Et2O/hexane 1/1) to give
3
(s), 139.5 (s), 132.8-123.0 (m), 113.4 (d, J PC ) 17.5 Hz); 31P
NMR (CDCl3, 120 MHz) δ 1.30; IR (KBr) 1386; MS (EI) m/ z
461 (M+, 10). Anal. Calcd for C30H24NSP: C, 78.07; H, 5.25;
N, 3.04. Found: C, 78.02; H, 5.27; N, 3.04.
1,1,1,4-Tetr aph en yl-3-(3-pyr idyl)-2-aza-1λ5-ph osph abu ta-
1,3-d ien e (4d ). The general procedure was followed using

Reaction of N-Vinylic Phosphazenes with CO Compounds
J . Org. Chem., Vol. 62, No. 4, 1997 1151
0.984 g (60%) of a 50:50 diastereomeric mixture of E/Z isomers
of 1bc as a yellow oil (Rf ) 0.42): 1H NMR (300 MHz, CDCl3)
δ 10.34 (s, 1H),10.10 (s, 1H), 8.60-8.54 (m, 2H), 8.52 (s, 1H)
for the E-isomer, 8.45 (s, 1H) for the Z-isomer 7.74-7.00 (m,
24 H), 6.80 (s, 1H) for the Z-isomer, 6.42 (s, 1H) for the
E-isomer. Anal. Calcd for C21H16N2S: C, 76.80; H, 4.91; N,
8.53. Found: C, 76.02; H, 4.90 N, 8.50.
(3Z)-1,3-Bis-(2-t h ien yl)-4-p h en yl-2-a za b u t a -1,3-d ien e
(1bd ). The general procedure was followed using 2-thiophen-
ecarboxaldehyde (0.460 mL, 5 mmol) and 2.305 g (5 mmol) of
phosphazene 4b (40 h). The crude oil was chromatographed
on neutral aluminum oxide (Et2O/hexane 1/1) to give 1.032 g
(70%) of a 40:60 diastereomeric mixture of E/Z isomers of 1bd
as a yellow oil (Rf ) 0.59): 1H NMR (300 MHz, CDCl3) δ 8.52
(s, 1H) for the E-isomer, 8.24 (s, 1H) for the Z-isomer, 7.65-
6.96 (m, 23 H), 6.44 (s, 1H) for the E-isomer. Anal. Calcd for
C17H13NS2: C, 69.13; H, 4.44; N, 4.75. Found: C, 69.08; H,
4.46; N, 4.74.
(3Z)-1,3,4-Tr iph en yl-2-azabu ta-1,3-dien e (1ca). The gen-
eral procedure was followed using benzaldehyde (0.505 mL, 5
mmol) and 2.275 g (5 mmol) of phosphazene 4c (24 h). The
crude oil was chromatographed on neutral aluminum oxide
(Et2O/hexane 1/2) to give 1.344 g (95%) of a (40:60) diastere-
omeric mixture of E/Z isomers of 1ca as a yellow oil (Rf )
0.54): 1H NMR (300 MHz, CDCl3) δ 8.30 (s, 1H) for the
E-isomer, 8.02 (s, 1H) for the Z-isomer 7.87-6.95 (m, 31 H),
6.48 (s, 1H) for the E-isomer. Anal. Calcd for C21H17N: C,
89.00; H, 6.05; N, 4.95. Found: C, 88.97; H, 6.06; N, 4.97.
Calcd for C19H16N2: C, 83.78; H, 5.93; N, 10.29. Found: C,
83.80; H, 5.92; N, 10.28.
(3Z)-3,4-Diph en yl-1-(3-in dolyl)-2-azabu ta-1,3-dien e (1cf).
The general procedure was followed using 3-indolecarboxal-
dehyde (0.726 g, 5 mmol) and 2.275 g (5 mmol) of phosphazene
4c (136 h). The crude oil was chromatographed on neutral
aluminum oxide (Et2O/hexane 1/2) to give 0.998 g (62%) of a
40:60 diastereomeric mixture of E/Z isomers of 1cf as a yellow
oil (Rf ) 0.17): 1H NMR (300 MHz, CDCl3) δ 10.12 (s, 1H),
10.02 (s, 1H), 8.55 (m, 1H), 8.48 (m, 1H), 8.29 (s, 1H) for the
E-isomer, 8.14 (s, 1H) for the Z-isomer, 7.76-6.90 (m, 28 H),
6.84 (s, 1H) for the Z-isomer, 6.29 (s, 1H) for the E-isomer.
Anal. Calcd for C23H18N2: C, 85.68; H, 5.63; N, 8.69. Found:
C, 85.65; H, 5.65; N, 8.70.
(3Z)-1,4-Dip h e n yl-3-(3-p yr id yl)-2-a za b u t a -1,3-d ie n e
(1d a ). The general procedure was followed using benzalde-
hyde (0.505 mL, 5 mmol) and 2.280 g (5 mmol) of phosphazene
4d (63 h). The crude oil was chromatographed on neutral
aluminum oxide (Et2O/hexane 1/1) to give 1.150 g (81%) of an
80:20 diastereomeric mixture of E/Z isomers of 1d a as a yellow
oil (Rf ) 0.48): 1H NMR (300 MHz, CDCl3) δ 8.75 (s, 1H), 8.56
(m, 2H), 8.25 (s, 1H) for the E-isomer, 8.1 (s, 1H) for the
Z-isomer, 8.09-7.05 (m, 25H), 6.92 (s, 1H) for the Z-isomer,
6.42 (s, 1H) for the E-isomer. Anal. Calcd for C20H16N2: C,
84.47; H, 5.68; N, 9.86. Found: C, 84.44; H, 5.68; N, 9.88.
(3Z)-4-P h en yl-1,3-b is(3-p yr id yl)-2-a za b u t a -1,3-d ien e
(1d b). The general procedure was followed using 3-pyridin-
ecarboxaldehyde (0.472 mL, 5 mmol) and 2.280 g (5 mmol) of
phosphazene 4d (15 h). The crude oil was chromatographed
on neutral aluminum oxide (AcOEt) to give 1.411 g (99%) of a
50:50 diastereomeric mixture of E/Z isomers of 1d b as a yellow
oil (Rf ) 0.12): 1H NMR (300 MHz, CDCl3) δ 8.97-8.53 (m, 6
H), 8.28 (s, 1H) for the E-isomer, 8.09 (s, 1H) for the Z-isomer,
7.74-7.00 (m, 19 H), 6.47 (s, 1H) for the E-isomer. Anal.
Calcd for C19H15N3: C, 79.97; H, 5.30; N, 14.73. Found: C,
79.95; H, 5.31; N, 14.74.
(3Z)-3,4-Dip h e n yl-1-(3-p yr id yl)-2-a za b u t a -1,3-d ie n e
(1cb). The general procedure was followed using 3-pyridine-
carboxaldehyde (0.472 mL, 5 mmol) and 2.275 g (5 mmol) of
phosphazene 4c (15 h). The crude oil was chromatographed
on neutral aluminum oxide (Et2O/hexane 1/1) to give 0.944 g
(70%) of a 50:50 diastereomeric mixture of E/Z isomers of 1cb
as a yellow oil (Rf ) 0.35): 1H NMR (300 MHz, CDCl3) δ 8.96
4
4
3
(d, J HH ) 2 Hz, 1H), 8.85 (d, J HH ) 2 Hz, 1H), 8.70 (dd, J HH
(3Z)-1-(5-Meth yl-2-fu r yl)-4-p h en yl-3-(3-p yr id yl)-2-a za b-
u ta -1,3-d ien e (1d c). The general procedure was followed
using 5-methyl-2-furfural (0.497 mL, 5 mmol) and 2.280 g (5
mmol) of phosphazene 4d (66 h). The crude oil was chromato-
graphed on neutral aluminum oxide (AcOEt) to give 0.518 g
(36%) of the E-isomer and 0.777 g (54%) of the Z -isomer of
1d c as yellow oils (Rf ) 0.33 for the E-isomer and Rf ) 0.43
for the Z -isomer). Data for E-isomer:1H NMR (300 MHz,
CDCl3) δ 8.62 (m, 1H), 8.42 (dd, 3J HH ) 1.5 Hz, 3J HH ) 0.9 Hz,
1H), 7.81 (s, 1H), 7.8-6.8 (m, 6H), 6.68 (d, 3J HH ) 3.6 Hz, 1H),
6.25 (s, 1H), 6.05 (m, 1H), 2.3 (s, 3H). Anal. Calcd. for
C19H16N2O: C, 79.13; H, 5.60; N, 9.72. Found: C, 79.00; H,
5.58; N, 9.70.
4
3
4
) 4.8 Hz, J HH ) 2 Hz, 1H), 8.62 (dd, J HH ) 4.8 Hz, J HH ) 2
Hz, 1H), 8.30 (s, 1H) for the E-isomer, 8.28-8.19 (m, 2H),
7.71-7.04 (m, 23 H), 6.46 (s, 1H) for the E-isomer. Anal.
Calcd for C20H16N2: C, 84.47; H, 5.68; N, 9.86. Found: C,
84.51; H, 5.66; N, 9.83.
(3Z)-3,4-Dip h en yl-1-(5-m et h yl-2-fu r yl)-2-a za b u t a -1,3-
d ien e (1cc). The general procedure was followed using
5-methyl-2-furfural (0.497 mL, 5 mmol) and 2.275 g (5 mmol)
of phosphazene 4c (144 h). The crude oil was chromato-
graphed on neutral aluminum oxide (Et2O/hexane 1/2) to give
0.861 g (60%) of a 40:60 diastereomeric mixture of E/Z isomers
of 1cc as a yellow oil (Rf ) 0.35): 1H NMR (300 MHz, CDCl3)
δ 7.93 (s, 1H) for the E-isomer, 7.72 (m, 2H), 7.62 (s, 1H) for
Data for Z-isomer: 1H NMR (300 MHz, CDCl3) δ 8.65 (dd,
3
the Z-isomer, 7.45-6.92 (m, 21 6H), 6.72 (d, J HH ) 3.3Hz,
3
3
3
3J HH ) 4.8 Hz, J HH ) 1.8 Hz, 1H), 8.5 (dd, J HH ) 2 Hz, J HH
3
1H), 6.56 (d, J HH ) 3.3Hz, 1H), 6.32 (s, 1H) for the E-isomer,
3
) 1 Hz, 1H), 7.7 (s, 1H), 7.6-6.9 (m, 7H), 6.67 (d, J HH ) 3.3
3
3
6.10 (d, J HH ) 3.3Hz, 1H), 6.05 (d, J HH ) 3.3 Hz, 1H), 2.38
(s, 3H), 2.36 (s, 3H). Anal. Calcd for C20H17NO: C, 83.59; H,
5.97; N, 4.88. Found: C, 83.50; H, 5.98; N, 4.87.
Hz, 1H), 6.12 (m, 1H), 2.4 (s, 3H). Anal. Calcd for
C19H16N2O: C, 79.13; H, 5.60; N, 9.72. Found: C, 78.98; H,
5.61; N, 9.70.
(3Z)-3,4-Dip h e n yl-1-(2-t h ie n yl)-2-a za b u t a -1,3-d ie n e
(1cd ). The general procedure was followed using 2-thiophene-
carboxaldehyde (0.460 mL, 5 mmol) and 2.275 g (5 mmol) of
phosphazene 4c (14 h). The crude oil was chromatographed
on neutral aluminum oxide (Et2O/hexane 1/1) to give 1.300 g
(90%) of a 40:60 diastereomeric mixture of E/Z isomers of 1cd
as a yellow oil (Rf ) 0.74): 1H NMR (300 MHz, CDCl3) δ 8.16
(s, 1H) for the E-isomer, 7.89 (s, 1H) for the Z-isomer, 7.63-
6.79 (m, 27 H), 6.20 (s, 1H) for the E-isomer. Anal. Calcd for
C19H15NS: C, 78.86; H, 5.23; N, 4.84. Found: C, 78.66; H,
5.22; N, 4.86.
(3Z)-3,4-Dip h en yl-1-(2-p yr r olyl)-2-a za b u t a -1,3-d ien e
(1ce). The general procedure was followed using 2-pyrrole-
carboxaldehyde (0.475 g, 5 mmol) and 2.275 g (5 mmol) of
phosphazene 4c (192 h). The crude oil was chromatographed
on neutral aluminum oxide (Et2O/hexane 1/2) to give 0.970 g
(77%) of a 50:50 diastereomeric mixture of E/Z isomers of 1ce
as a yellow oil (Rf ) 0.34): 1H NMR (300 MHz, CDCl3) δ 10.00
(s,1H), 8.09-7.96 (m, 3H), 7.70 (s, 1H) for the Z-isomer, 7.60-
6.70 (m, 21 H), 6.55 (d, 3J HH ) 3.6 Hz, 1H), 6.42 (d, 3J HH ) 3.6
Hz, 1H), 6.36 (s, 1H) for the E-isomer, 6.26-6.17 (m, 2H). Anal.
Gen er a l P r oced u r e for th e P r ep a r a tion of Isoqu in o-
lin es 2. A solution of 2-azadiene (5 mmol) in xylene (20 mL)
was warmed at 140 °C under N2. Evaporation of solvent under
reduced pressure afforded an oil that was chromatographed
on silica gel to give the isoquinolines 2.
3-(2-F u r yl)-1-p h en yl isoqu in olin e (2a ). The general
procedure was followed using 1.365 g (5 mmol) of 2-azadiene
1a a , and the solution was warmed for 12 h. The crude oil was
chromatographed on silica gel (hexane/Et2O 10/1) to give 1.125
g (83%) of 2a as a yellow solid: mp 149-150 °C (recrystallized
from hexane/CH2Cl2); 1H NMR (300 MHz, CDCl3) δ 8.08-7.25
3
3
(m, 11 H), 7.18 (d, J HH ) 3.3 Hz, 1H), 6.55 (dd, J HH ) 1.8
Hz, J HH ) 3.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 160.7,
3
154.6, 142.9, 139.5-113.5 (m), 112.1, 108.6; IR (KBr) 1616,
1558, 1484, 1010; M/S (EI) m/ z 271 (M+, 100). Anal. Calcd
for C19H13NO: C, 84.11; H, 4.83; N, 5.16. Found: C, 84.01;
H, 4.82; N, 5.18.
1-(3-P yr id yl)-3-(2-th ien yl)isoqu in olin e (2b). The gen-
eral procedure was followed using 1.450 g (5 mmol) of 2-aza-
diene 1bb, and the solution was warmed for 15 h. The crude
oil was chromatographed on silica gel (hexane/Et2O 5/1) to give

1152 J . Org. Chem., Vol. 62, No. 4, 1997
Palacios et al.
1.008 g (70%) of 2b as a white solid: mp 132-133 °C
1743, 1216, 1117; M/S (EI) m/ z 381 (M+, 5). Anal. Calcd for
C22H23NO5: C, 69.28; H, 6.08; N, 3.67. Found: C, 69.09; H,
6.07; N, 3.68.
(recrystallized from hexane/CH2Cl2); 1H NMR (300 MHz,
4
3
CDCl3) δ 8.99 (d, J HH ) 1.5 Hz, 1H), 8.70 (dd, J HH ) 4.7 Hz,
4J HH ) 1.5 Hz, 1H), 8.10-7.08 (m, 10 H); 13C NMR (75 MHz,
CDCl3) δ 157.4, 151.2, 150.0, 146.2-123.5 (m), 114.4; IR (KBr)
1606, 1557, 1430, 1050; M/S (EI) m/ z 288 (M+, 83). Anal.
Calcd for C18H12N2S: C, 74.97; H, 4.19; N, 9.72. Found: C,
74.79; H, 4.20; N, 9.71
Gen er a l P r oced u r e A for th e P r ep a r a tion of 11. To a
solution of 2-azadiene 1 (5 mmol) in CHCl3 (20 mL) was added
0.510 g (5 mmol) of freshly distilled ethyl glyoxalate, and the
mixture was refluxed at 80 °C for 144 h under N2. Evaporation
of solvent under reduced pressure afforded an oil that was
chromatographed on silica gel to give the compounds 11.
Gen er a l P r oced u r e B for th e P r ep a r a tion of 11. To a
solution of 2-azadiene 1 (5 mmol) in Et2O (10 mL) were added
0.510 g (5 mmol) of freshly distilled ethyl glyoxalate and 5.320
g (0.050 mol) of LiClO4. The mixture was stirred at rt under
N2 and was poured on CH2Cl2 (20 mL), washed with a satured
solution of NaHCO3, extracted with three 20 mL portions of
CH2Cl2, and dried (MgSO4). Evaporation of solvent under
reduced pressure afforded an oil that was chromatographed
on silica gel to give the compounds 11.
3-P h en yl-1-(3-p yr id yl) isoqu in olin e (2c). The general
procedure was followed using 1.420 g (5 mmol) of a 50:50
diastereomeric mixture of E/Z isomers of 2-azadiene 1cb, and
the solution was warmed for 15 h. The crude oil was
chromatographed on silica gel (hexane) to give 1.156 g (82%)
of 2c as a yellow solid: mp 51-52 °C (recrystallized from
4
hexane/CH2Cl2); 1H NMR (300 MHz, CDCl3) δ 9.07 (d, J HH
)
2.1Hz, 1H), 8.76 (dd, 4J HH ) 2.1 Hz, 3J HH ) 4.8 Hz, 1H), 8.22-
7.20 (m, 12 H); 13C NMR (75 MHz, CDCl3) δ 157.1, 150.8-
123.3 (m), 116.2; IR (KBr) 1622, 1575, 1390, 1031; M/S (EI)
m/ z 282 (M+, 70). Anal. Calcd for C20H14N2: C, 85.08; H, 5.00;
N, 9.92. Found: C, 85.28; H, 5.02; N, 9.92.
6-(Eth oxycar bon yl)-2-(3-pyr idyl)-4-(2-fu r yl)-5,6-dih ydr o-
2H-1,3-oxa zin es (11a ). The general procedure A was fol-
lowed using 2.225 g (5 mmol) of 2-azadiene 1a b. The crude
oil was chromatographed on silica gel (hexane) to give 1.428 g
(76%) of 11a as a white solid. Following the general procedure
B 2.225 g (5 mmol) of 2-azadiene 1a b was used for 20 h, and
the crude oil was chromatographed on silica gel (hexane) to
give 1.362 g (78%) of 11a as a white solid: mp 150-152 °C
(recrystallized from hexane/Et2O); 1H NMR (300 MHz, CDCl3)
δ 9.01 (s, 1H), 8.65 (m, 1H), 8.04 (m, 1H), 7.71-7.23 (m, 7 H),
1-P h en yl-3-(3-p yr id yl)isoqu in olin e (2d ). The general
procedure was followed using 1.420 g (5 mmol) of an 80:20
diastereomeric mixture of E/Z isomers of 2-azadiene 1d a , and
the solution was warmed for 17 h. The crude oil was
chromatographed on silica gel (hexane/Et2O 1/1) to give 1.100
g (78%) of 2d as a brown oil (Rf ) 0.39 in AcOEt): 1H NMR
(300 MHz, CDCl3) δ 9.07 (d, 4J HH ) 2.2Hz, 1H), 8.55 (dd, 3J HH
3
) 2.4 Hz, J HH ) 4.7 Hz, 1H), 8.10 (m, 1H), 8.02-7.05 (m, 11
H); 13C NMR (75 MHz, CDCl3) δ 154.0, 152.8, 150.1, 149.8,
140.8-122.5 (m); IR (film) 1680, 1591, 1196, 1124; M/S (EI)
m/ z 282 (M+, 40). Anal. Calcd for C20H14N2: C, 85.08; H, 5.00;
N, 9.92. Found: C, 85.28; H, 5.00; N, 9.93.
5
3
6.78 (d, J HH ) 2.4 Hz, 1H), 6.39 (m, 2H), 4.92 (d, J HH ) 3.2
5
3
Hz, 1H), 4.38 (dd, J HH ) 2.4 Hz, J HH ) 3.2 Hz, 1H), 4.04-
3.90 (m, 2H), 1.25 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 167.9,
154.8-144.8 (m), 135.2-123.2 (m), 113.8, 111.9, 87.3, 75.3,
61.3, 44.2, 14.1; IR (KBr) 1732, 1437, 1188, 1120; M/S (EI) m/ z
376 (M+, 6). Anal. Calcd for C22H20N2O4: C, 70.20; H, 5.36;
N, 7.44. Found: C, 70.10; H, 5.35; N, 7.43
Gen er a l P r oced u r e for th e P r ep a r a tion of 9. To a
solution of phosphazene 4 (5 mmol) in CHCl3 (20 mL) was
added 1.020 g (10 mmol) of freshly distilled ethyl glyoxalate,
and the mixture was stirred at rt under N2. Evaporation of
solvent under reduced pressure afforded an oil that was
chromatographed on silica gel to give the compounds 9.
2,6-Bis(eth oxyca r bon yl)-4-(2-fu r yl)-5-p h en yl-5,6-d ih y-
d r o-2H-1,3-oxa zin es (9a ). The general procedure was fol-
lowed using 2.225 g (5 mmol) of phosphazene 4a , and the
mixture was stirred for 12 h. The crude oil was chromato-
graphed on silica gel (AcOEt/hexane 1/1) to give 1.336 g (72%)
of 9a as a brown oil (Rf ) 0.30); 1H NMR (300 MHz, CDCl3) δ
6-(E t h oxyca r b on yl)-2-(3-p yr id yl)-4-(2-t h ien yl)-5,6-d i-
h yd r o-2H-1,3-oxa zin es (11b). The general procedure A was
followed using 2.305 g (5 mmol) of 2-azadiene 1bb. The crude
oil was chromatographed on silica gel (hexane) to give 1.274 g
(65%) of 11b as a white solid. Following the general procedure
B 2.305 g (5 mmol) of 2-azadiene 1bb was used for 14 h, and
the crude oil was chromatographed on silica gel (hexane) to
give 1.372 g (70%) of 11b as a white solid: mp 162-163 °C
(recrystallized from hexane/Et2O); 1H NMR (300 MHz, CDCl3)
3
3
3
3
δ 8.97 (d, J HH ) 2.0 Hz, 1H), 8.58 (dd, J HH ) 4.9 Hz, J HH
)
7.36-7.10 (m, 6 H), 6.72 (d, J HH ) 3.5 Hz, 1H), 6.31 (m,1H),
1.7 Hz, 1H), 8.00 (dd, 3J HH ) 7.9 Hz, 3J HH ) 2.0 Hz, 1H), 7.35-
6.84 (m, 9 H), 6.30 (d, J HH ) 2.4 Hz, 1H), 4.80 (d, J HH ) 3.7
Hz, 1H), 4.35 (dd, J HH ) 2.4 Hz, J HH ) 3.7 Hz, 1H), 4.06-
3.98 (m, 2H), 1.01 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 165.2,
164.4, 149.6-117.0 (m), 87.8, 75.2, 61.2, 44.8,14.0; IR (KBr)
1754, 1630, 1210; M/S (EI) m/ z 392 (M+, 5). Anal. Calcd for
C22H20N2O3S: C, 67.33; H, 5.14; N, 7.14. Found: C, 67.30; H,
5.13; N, 7.14.
3
6.12 (s,1H), 5.33 (d, J HH ) 3.5 Hz, 1H), 4.32-4.20 (m, 3H),
5
3
4.10-3.85 (m, 2H), 1.25 (t, 3H), 1.00 (t, 3H); 13C NMR (75 MHz,
CDCl3) δ 168.2, 158.0,144.8-128.0 (m), 113.9, 111.7, 85.6, 70.4,
61.9, 61.2, 43.1, 14.1, 14.0; IR (film) 1759, 1750, 1632, 1232,
1197; M/S (EI) m/ z 371 (M+, 5). Anal. Calcd for C20H21NO6:
C, 64.68; H, 5.70; N, 3.77. Found: C, 64.58; H, 5.68; N, 3.78.
2,6-Bis(eth oxyca r bon yl)-5-p h en yl-4-(2-th ien yl)-5,6-d i-
h yd r o-2H-1,3-oxa zin es (9b). The general procedure was
followed using 2.305 g (5 mmol) of phosphazene 4b, and the
mixture was stirred for 48 h. The crude oil was chromato-
graphed on silica gel (hexane) to give 1.160 g (60%) of 9b as a
white solid: mp 125-126 °C (recrystallized from hexane/Et2O);
1H NMR (300 MHz, CDCl3) δ 7.28-6.85 (m, 8 H), 6.03 (s,1H),
5.31 (d, 3J HH ) 3.4 Hz, 1H), 4.30 (d, 3J HH ) 3.4 Hz, 1H), 4.31-
5
3
6-(Eth oxycar bon yl)-2-(3-pyr idyl)-4-ph en yl-5,6-dih ydr o-
2H-1,3-oxa zin es (11c). The general procedure A was followed
using 2.275 g (5 mmol) of a 50:50 diastereomeric mixture of
E/Z isomers of 2-azadiene 1cb. The crude oil was chromato-
graphed on silica gel (hexane) to give 1.216 g (63%) of 11c as
a white solid. Following the general procedure B 2.275 g (5
mmol) of 2-azadiene 1cb was used for 18 h, and the crude oil
was chromatographed on silica gel (hexane) to give 1.255 g
(65%) of 11c as a white solid: mp 148-149 °C (recrystallized
from hexane/Et2O); 1H NMR (300 MHz, CDCl3) δ 9.11 (s, 1H),
8.69 (d, 3J HH ) 4.8 Hz, 1H), 8.17 (d, 3J HH ) 6.3 Hz, 1H), 7.92-
7.19 (m, 11 H), 6.44 (d, 5J HH ) 2.1 Hz, 1H), 4.88 (d, 3J HH ) 3.6
4.17 (m, 2H), 4.09-3.85 (m, 2H), 1.26 (t, 3H), 1.03 (t, 3H); 13
C
NMR (75 MHz, CDCl3) δ 168.2, 160.1, 135.0, 129.9, 129.1-
127.5 (m), 85.5, 70.7, 61.9, 61.2, 44.4, 14.1, 14.0; IR (KBr) 1762,
1631, 1229, 1196, 1111; M/S (EI) m/ z 387 (M+, 3). Anal. Calcd
for C20H21NO5S: C, 62.00; H, 5.46; N, 3.62. Found: C, 62.18;
H, 5.47; N, 3.62.
5
3
Hz, 1H), 4.51 (d, J HH ) 2.1 Hz, J HH ) 3.6 Hz, 1H), 4.07-
3.99 (m, 2H), 1.14 (t, 3H); 13C NMR (75 MHz, CDCl3) δ 165.4,
164.8, 150.1-120.3 (m), 88.1, 74.9, 61.0, 44.5,14.1; IR (KBr)
1762, 1631, 1210; M/S (EI) m/ z 386 (M+, 5).
2,6-Bis(eth oxyca r bon yl)-4,5-d ip h en yl-5,6-d ih yd r o-2H-
1,3-oxa zin es (9c). The general procedure was followed using
2.275 g (5 mmol) of phosphazene 4c, and the mixture was
stirred for 68 h. The crude oil was chromatographed on silica
gel (hexane/AcOEt: 5/1) to give 0.762 g (80%) of 9c as a white
Anal. Calcd for C24H22N2O3: C, 74.59; H, 5.74; N, 7.25.
Found: C, 74.69; H, 5.73; N, 7.24.
1
solid: mp 138-140 °C (recrystallized from hexane/Et2O); H
NMR (300 MHz, CDCl3) δ 7.81-7.20 (m, 10 H), 6.23 (s,1H),
Gen er a l P r oced u r e for th e P r ep a r a tion of 12. To a
solution of 2-azadiene 1 (5 mmol) in Et2O (10 mL) were added
0.762 mL of diethyl ketomalonate and 5.320 g (0.050 mol) of
LiClO4. The mixture was stirred at rt under N2 and was
poured on CH2Cl2 (20 mL), washed with a satured solution of
5.36 (d, 3J HH ) 3.3 Hz, 1H), 4.43 (d, 3J HH ) 3.3 Hz, 1H), 4.39-
4.21 (m, 2H), 4.08-3.92 (m, 2H), 1.36 (t, 3H), 1.10 (t, 3H); 13
C
NMR (75 MHz, CDCl3) δ 168.5, 164.9, 136.7, 134.9, 131.0-
127.3 (m), 86.3, 71.2, 62.0, 61.3, 43.8, 14.3, 14.1; IR (KBr) 1768,

Reaction of N-Vinylic Phosphazenes with CO Compounds
J . Org. Chem., Vol. 62, No. 4, 1997 1153
5
NaHCO3, extracted with three 20 mL portions of CH2Cl2, and
dried (MgSO4). Evaporation of solvent under reduced pressure
afforded an oil that was chromatographed on silica gel to give
the compounds 12.
1H), 8.10 (m, 1H), 7.78-7.09 (m, 11 H), 6.31 (d, J HH ) 2.4
3
Hz, 1H), 4.92 (d, J HH ) 2.4 Hz, 1H), 4.30 (m, 2H), 4.00 (m,
2H), 1.22 (t, 3H), 1.00 (t, 3H). Anal. Calcd for C27H26N2O5:
C, 70.73; H, 5.72; N, 6.11. Found: C, 70.62; H, 5.72; N, 6.13.
6,6-Bis(eth oxyca r bon yl)-4-(2-fu r yl)-2,5-d ip h en yl-5,6-d i-
h yd r o-2H-1,3-oxa zin es (12a ). The general procedure was
followed using 1.365 g (5 mmol) of 2-azadiene 1a a for 4 h. The
crude oil was chromatographed on silica gel (hexane/AcOEt
5/1) to give 1.743 g (78%) of 12a as a white solid: mp 148-
149 °C (recrystallized from hexane/CH2Cl2); 1H NMR (300
6,6-Bis(et h oxyca r b on yl)-4,5-d ip h en yl-2-(5-m et h yl-2-
fu r yl)-5,6-d ih yd r o-2H-1,3-oxa zin es (12g). The general pro-
cedure was followed using 1.435 g (5 mmol) of a 40:60
diastereomeric mixture of E/Z isomers of 2-azadiene 1cc for
17 h. The crude oil was chromatographed on silica gel (hexane/
AcOEt 10/1) to give 1.567 g (68%) of a 70:30 diastereomeric
mixture of 12g and 12g′ as a white solid: mp 142-144 °C
5
MHz, CDCl3) δ 7.74-7.13 (m, 11 H), 6.71 (d, J HH ) 2.7 Hz,
1H), 6.34-6.14 (m, 2H), 4.72 (d, 5J HH ) 2.7 Hz,1H), 4.31-4.18
(m, 2H), 4.00-3.78 (m, 2H), 1.24 (t, 3H), 0.95 (t, 3H). Anal.
Calcd for C26H25NO6: C, 69.79; H, 5.63; N, 3.13. Found: C,
69.88; H, 5.61; N, 3.13.
(recrystallized from hexane/Et2O); 1H NMR (300 MHz, CDCl3)
3
δ 7.88-7.18 (m, 20 H), 6.89 (s, 1H) for 12g′, 6.50 (d, J HH
)
5
3
3.1 Hz, 1H), 6.28 (d, J HH ) 2.4 Hz, 1H) for 12g, 6.09 (d, J HH
3
) 3.0 Hz, 1H), 6.03 (m, 1H), 5.88 (d, J HH ) 3.0 Hz, 1H), 4.93
6,6-B is (e t h o x y c a r b o n y l)-4-(2-fu r y l)-5-p h e n y l-2-(3-
p yr id yl)-5,6-d ih yd r o-2H-1,3-oxa zin es (12b). The general
procedure was followed using 1.370 g (5 mmol) of 2-azadiene
1a b for 1 h. The crude oil was chromatographed on silica gel
(hexane/AcOEt 5/1) to give 1.389 g (62%) of 12b as a yellow
solid: mp 173-174 °C (recrystallized from hexane/CH2Cl2); 1H
5
(d, J HH ) 2.4 Hz, 1H) for 12g, 4.86 (s, 1H) for 12g′, 4.40-
4.25 (m, 2H), 4.07-3.86 (m, 5H), 3.52-3.46 (m, 1H), 2.37 (s,
3H), 2.32 (s, 3H), 1.30 (t, 3H), 1.05-0.98 (m, 9H). Anal. Calcd
for C27H27NO6: C, 70.27; H, 5.90; N, 3.03. Found: C, 70.20;
H, 5.88; N, 3.01.
6,6-Bis(eth oxyca r bon yl)-4,5-d ip h en yl-2-(2-th ien yl)-5,6-
d ih yd r o-2H-1,3-oxa zin es (12h ). The general procedure was
followed using 1.445 g (5 mmol) of a 40:60 diastereomeric
mixture of E/Z isomers of 2-azadiene 1cd for 96 h. The crude
oil was chromatographed on silica gel (hexane/AcOEt 2/1) to
give 1.984 g (88%) of a (70:30) diastereomeric mixture of 12h
and 12h ′ as a brown oil (Rf ) 0.41): 1H NMR (300 MHz, CDCl3)
3
NMR (300 MHz, CDCl3) δ 8.99 (d, J HH ) 1.5 Hz, 1H), 8.59
3
3
3
(dd, J HH ) 3.3 Hz, J HH ) 1.5 Hz, 1H), 8.03 (dd, J HH ) 8.1
3
5
Hz, J HH ) 2.1 Hz, 1H), 7.36-7.13 (m, 7 H), 6.75 (d, J HH
)
3
3
2.7 Hz, 1H), 6.30 (dd, J HH ) 3.0 Hz, J HH ) 1.5 Hz, 1H), 6.25
3
5
(d, J HH ) 3.0 Hz, 1H), 4.75 (d, J HH ) 2.7 Hz, 1H), 4.30 (q,
2H), 3.96-3.82 (m, 2H), 1.25 (t, 3H), 0.96 (t, 3H). Anal. Calcd
for C25H24N2O6: C, 66.96; H, 5.39; N, 6.25. Found: C, 67.00;
H, 5.37; N, 6.23.
5
δ 7.95-6.95 (m, 27 H), 6.54 (d, J HH ) 2.4 Hz, 1H) for 12h ,
4.98 (d, 5J HH ) 2.4 Hz, 1H) for 12h , 4.80 (s, 1H) for 12h ′, 4.42-
4.80 (m, 2H), 4.03-3.81 (m, 4H), 3.75 (m, 1H), 3.25 (m, 1H),
6,6-Bis(eth oxyca r bon yl)-4-(2-fu r yl)-5-p h en yl-2-(2-p yr -
r olyl)-5,6-d ih yd r o-2H-1,3-oxa zin es (12c). The general pro-
cedure was followed using 1.310 g (5 mmol) of 2-azadiene 1a c
for 1 h. The crude oil was chromatographed on silica gel
(hexane/AcOEt 5/1) to give 1.264 g (58%) of 12c as a yellow
1.32 (t, 3H), 1.09-0.96 (m, 9H). Anal. Calcd for C25H25
-
NO5S: C, 66.50; H, 5.58; N, 3.10. Found: C, 66.43; H, 5.57;
N, 3.12.
1
solid: mp 198-199 °C (recrystallized from hexane/Et2O); H
6,6-Bis(eth oxyca r bon yl)-4,5-d ip h en yl-2-(3-in d olyl)-5,6-
d ih yd r o-2H-1,3-oxa zin es (12i). The general procedure was
followed using 1.440 g (5 mmol) of a 40:60 diastereomeric
mixture of E/Z isomers of 2-azadiene 1cf for 48 h. The crude
oil was chromatographed on silica gel (hexane/AcOEt 5/1) to
give 1.562 g (63%) of 12i as a white solid: mp 78-80 °C
(recrystallized from hexane/Et2O); 1H NMR (300 MHz, CDCl3)
δ 8.58 (s, 1H), 8.08-6.86 (m, 15H), 6.65 (d, 5J HH ) 2.7 Hz, 1H),
4.96 (d, 5J HH ) 2.7 Hz, 1H), 4.40-4.12 (m, 2H), 4.08-3.86 (m,
2H), 1.97-1.30 (m, 6H). Anal. Calcd for C30H28N2O5: C, 72.56;
H, 5.68; N, 5.64. Found: C, 72.59; H, 5.67; N, 5.63.
NMR (300 MHz, CDCl3) δ 9.34 (s, 1H), 7.70-7.19 (m, 11 H),
5
5
6.80 (d, J HH ) 2.7 Hz, 1H), 6.49-6.34 (m, 4H), 4.76 (d, J HH
) 2.7 Hz, 1H), 4.37-4.26 (m, 2H), 4.03-3.88 (m, 2H),1.28 (t,
3H), 1.02 (t, 3H). Anal. Calcd for C24H24N2O6: C, 66.04; H,
5.54; N, 6.42. Found: C, 66.24 H, 5.53; N, 6.41.
6,6-Bis(eth oxyca r bon yl)-4-(2-th ien yl)-2,5-d ip h en yl-5,6-
d ih yd r o-2H-1,3-oxa zin es (12d ). The general procedure was
followed using 1.445 g (5 mmol) of a 50:50 diastereomeric
mixture of E/Z isomers of 2-azadiene 1ba for 2 h. The crude
oil was chromatographed on silica gel (hexane/AcOEt 5/1) to
give 1.806 g (78%) of a 70:30 diastereomeric mixture of 12d
and 12d ′ as a white solid: mp 66-68 °C (recrystallized from
hexane/Et2O); 1H NMR (300 MHz, CDCl3) δ 7.86-6.95(m,
6,6-Bis(et h oxyca r b on yl)-5-p h en yl-2,4-b is(3-p yr id yl)-
5,6-d ih yd r o-2H-1,3-oxa zin es (12j). The general procedure
was followed using 1.425 g (5 mmol) of a 50:50 diastereomeric
mixture of E/Z isomers of 2-azadiene 1d b for 96 h. The crude
oil was chromatographed on silica gel (hexane/AcOEt 1/1) to
give 1.515 g (66%) of 12j as a white solid: mp 169-171 °C
(recrystallized from hexane/CH2Cl2); 1H NMR (300 MHz,
5
5
27H), 6.30 (d, J HH ) 2.4 Hz, 1H) for 12d , 4.90 (d, J HH ) 2.4
Hz, 1H) for 12d , 4.79 (s, 1H) for 12d ′, 4.43-4.36 (m, 2H), 4.11-
3.92 (m, 4H), 3.65 (m, 1H), 2.93 (m, 1H), 1.36 (t, 3H), 1.22-
1.01 (m, 6H), 0.90 (t, 3H). Anal. Calcd for C26H25NO5S: C,
67.37; H, 5.44; N, 3.02. Found: C, 67.28; H, 5.42; N, 3.01.
6,6-Bis(eth oxyca r bon yl)-4-(2-th ien yl)-5-p h en yl-2-(3-p y-
r id yl)-5,6-d ih yd r o-2H-1,3-oxa zin es (12e). The general pro-
cedure was followed using 1.450 g (5 mmol) of 2-azadiene 1bb
for 2 h. The crude oil was chromatographed on silica gel
(hexane/AcOEt 5/1) to give 0.998 g (43%) of a 70:30 diastere-
omeric mixture of 12e and 12e′ as a white solid: mp 116-
118 °C (recrystallized from hexane/Et2O); 1H NMR (300 MHz,
CDCl3) δ 9.01 (s, 1H), 8.84 (s, 1H), 8.60 (d, 3J HH ) 3.4 Hz, 1H),
3
3
CDCl3) δ 9.05 (d, J HH ) 1.5 Hz, 1H), 8.96 (d, J HH ) 1.5 Hz,
1H), 8.61 (m, 1H), 8.50 (m, 1H), 8.09 (m, 2H), 7.39-7.07 (m, 7
5
5
H), 6.30 (d, J HH ) 2.4 Hz, 1H), 4.85 (d, J HH ) 2.4 Hz, 1H),
4.30 (m, 2H), 4.00 (m, 2H), 1.25 (t, 3H), 0.99 (t, 3H). Anal.
Calcd for C26H25N3O5: C, 67.96; H, 5.48; N, 9.14. Found: C,
67.90; H, 5.47; N, 9.16.
6,6-Bis(eth oxyca r bon yl)-2-(5-m eth yl-2-fu r yl)-5-p h en yl-
4-(3-p yr id yl)-5,6-d ih yd r o-2H-1,3-oxa zin es (12k ). The gen-
eral procedure was followed using 1.440 g (5 mmol) of (1E,3Z)-
2-azadiene 1d c for 72 h. The crude oil was chromatographed
on silica gel (hexane/AcOEt 2/1) to give 1.271 g (55%) of a (70:
30) diastereomeric mixture of 12k and 12k ′ as a yellow solid:
mp 94-96 °C (recrystallized from hexane/Et2O); 1H NMR (300
3
3
8.48 (d, J HH ) 3.4 Hz, 1H), 8.05 (d, J HH ) 7.9 Hz, 1H), 7.84
3
5
(d, J HH ) 7.9 Hz, 1H), 7.37-6.85 (m, 19H), 6.24 (d, J HH
)
5
2.6 Hz, 1H) for 12e, 4.82 (d, J HH ) 2.6 Hz, 1H) for 12e, 4.69
(s, 1H) for 12e′, 4.34-4.24 (m, 2H), 4.03-3.83 (m, 4H), 3.60
(m, 1H), 2.95 (m, 1H), 1.26 (t, 3H), 0.98 (t, 6H), 0.79 (t, 3H).
Anal. Calcd for C25H24N2O5S: C, 64.64; H, 5.21; N, 6.03.
Found: C, 64.80; H, 5.23 N, 6.01.
3
MHz, CDCl3) δ 9.06 (s, 1H), 9.00 (s, 1H), 8.60 (d, J HH ) 4.5
3
3
Hz, 1H), 8.56 (d, J HH ) 4.8 Hz, 1H), 8.13 (d, J HH ) 7.5 Hz,
3
1H), 8.10 (d, J HH ) 8.1 Hz, 1H), 7.41-7.20 (m, 12 H), 6.90 (s,
6,6-Bis(eth oxyca r bon yl)-4,5-d ip h en yl-2-(3-p yr id yl)-5,6-
d ih yd r o-2H-1,3-oxa zin es (12f). The general procedure was
followed using 1.420 g (5 mmol) of a 50:50 diastereomeric
mixture of E/Z isomers of 2-azadiene 1cb for 4 h. The crude
oil was chromatographed on silica gel (hexane/AcOEt 5/1) to
give 1.832 g (80%) of 12f as a white solid: mp 105-106 °C
(recrystallized from hexane/CH2Cl2); 1H NMR (300 MHz,
3
5
1H) for 12k ′, 6.50 (d, J HH ) 3.00 Hz, 1H), 6.26 (d, J HH ) 2.7
3
3
Hz, 1H) for 12k , 6.07 (d, J HH ) 3.0 Hz, 1H), 6.05 (d, J HH
)
5
3.0 Hz, 1H), 5.89 (m, 1H), 4.85 (d, J HH ) 2.7 Hz, 1H) for the
12k , 4.81 (s, 1H) for 12k ′, 4.42-4.85 (m, 2H), 4.07-3.89 (m,
5H), 3.50 (m, 1H), 2.38 (s, 3H), 2.36 (s, 3H), 1.28-1.09 (m, 6H),
1.02-0.81 (m, 6H). Anal. Calcd for C26H26N2O6: C, 67.52; H,
5.67; N, 6.06. Found: C, 67.47 H, 5.66; N, 6.08.
3
3
CDCl3) δ 9.06 (d, J HH ) 1.5 Hz, 1H), 8.60 (d, J HH ) 4.8 Hz,

1154 J . Org. Chem., Vol. 62, No. 4, 1997
Palacios et al.
Su p p or tin g In for m a tion Ava ila ble: Additional spectral
data (13C NMR, IR, and MS) for compounds 1a a -1d c and
12a -12k (3 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
Ack n ow led gm en t. The present work has been
supported by Direccio´n General de Investigacio´n Cien-
t´ıfica y Te´cnica (DGICYT PB-93-0501) and by Departa-
mento de Educacio´n, Universidades e Investigacio´n del
Gobierno Vasco (PI 94-36). C.A. thanks the Departa-
mento de Educacio´n, Universidades e Investigacio´n del
Gobierno Vasco, for a Predoctoral Fellowship.
J O961664N