Synthesis of 1-phosphono-2-aza-1,3-dienes and scope of their aziridination

Article abstract of DOI:10.1055/s-2004-815969

Several 1-phosphono-2-aza-1,3-dienes 14 and 1-aryl-1-phosphono-2-aza-1,3- dienes 15-17 were prepared by 1,4-dehydrochlorination of the corresponding diethyl [(2-chloro-1-alkylidene)amino]methylphosphonates 10-13. 1-Phosphono-2-aza-1,3-dienes 14 react smoo

Full text of DOI:10.1055/s-2004-815969

722
PAPER
Synthesis of 1-Phosphono-2-aza-1,3-dienes and Scope of their Aziridination
S
ynthesis andA
z
a
iridination
r
of 1-Pho
t
sphono-2-aza
V
-1,3-dienes anderhoydonck, Christian V. Stevens*
Department of Organic Chemistry, Faculty of Agricultural and Applied Biological Sciences, Ghent University, Coupure Links 653,
9000 Ghent, Belgium
Fax +32(9)2646243; E-mail: Chris.Stevens@UGent.be
Received 22 December 2003; revised 19 January 2004
Synthesis of 1-Phosphono-2-aza-1,3-dienes
Abstract: Several 1-phosphono-2-aza-1,3-dienes 14 and 1-aryl-1-
phosphono-2-aza-1,3-dienes 15–17 were prepared by 1,4-dehydro-
chlorination of the corresponding diethyl [(2-chloro-1-alky-
lidene)amino]methylphosphonates 10–13. 1-Phosphono-2-aza-1,3-
In order to develop an entry towards 1-phosphono-2-aza-
1,3-dienes 14–17, diethyl aminomethylphosphonates
dienes 14 react smoothly with diazomethane to give 2-phosphono- were prepared using literature methods based on the Ka-
bachnik–Fields reaction.13,14
1-vinylaziridines 18. The synthesis of 2-ethoxycarbonyl-3-
phosphono-1-vinylaziridines 19 was performed using ethyl diazo-
acetate (EDA) in the presence of ytterbium(III) triflate as a catalyst.
The first step towards the synthesis of 1-phosphono-2-
aza-1,3-dienes 14–17 consists in the condensation of an
aliphatic aldehyde 1a–c with diethyl aminophosphonate
2–5 (Scheme 1). Diethyl aminophosphonates 2–5 were
reacted with a solution of aldehyde 1a–c in dichlo-
romethane in the presence of magnesium sulfate as a de-
hydrating agent. The resulting aldimines 6–9 were
isolated in good yields (92–99%) and could be used with-
out further purification (purity >96%). The aldimines 6–9
were then chlorinated at the a-position using 1.05 equiva-
lents of N-chlorosuccinimide (NCS) in refluxing carbon
tetrachloride. The a-chlorinated aldimines 10–13 were
obtained in excellent yields (95–99%). No purification
was required and the imines were used as such in the fol-
lowing step. The a-chlorinated aldimines 11a, 12a and
13a contained some unidentified products. However, dis-
tillation under reduced pressure of the chlorinated aldi-
mines 10–13 led to a serious loss of end product due to
partial decomposition.
2-Phosphono-3-(trimethylsilyl)aziridines 20 were prepared from
phosphonoazadienes 14 by treatment with (trimethylsilyl)di-
azomethane under reflux. 1-Aryl-1-phosphono-2-aza-1,3-dienes
are not susceptible to aziridination under these conditions.
Key words: 2-azadienes, 1-phosphono-2-azadienes, phospho-
noaziridines, diazo compounds, imines, Lewis acids, lanthanides
Introduction
The importance of acyclic a-aminophosphonates and a-
aminophosphonic acids is well established and they are
used in agrochemistry, pharmaceutical industry and in
protein research, because of their analogy to a-amino ac-
ids.1,2 However, heterocyclic phosphonates or phospho-
nates containing heterocyclic moieties are less studied
although examples of biologically active heterocyclic
phosphonates are appearing regularly in the literature. Im-
portant examples of such heterocyclic phosphonic acids
are phosphomycin (antibiotic),3,4 triazole substituted
phosphonic acid derivatives (herbicides),5 EB-1053 and
Theoretically, the sequence can also be inverted, starting
with the chlorination of aldehyde 1a–c followed by con-
densation with diethyl aminophosphonates 2–5. However,
this alternative reaction pathway resulted in the isolation
of impure chlorinated aldimines. Besides, purification of
this crude reaction mixture by distillation also resulted in
a considerable loss of product (yield: 35%).
CGP-42,446
(antiosteoporosis),6
phosphonometh-
ylmelamines (flame retardants),7 phosphonoalkylami-
notetrazole derivatives (endothelin converting enzyme
inhibitors),8 etc.
The a-chlorinated imines 10–13 were then treated with a
base in order to induce a 1,4-dehydrochlorination, yield-
ing the 1-phosphono-2-aza-1,3-dienes 14–17. A range of
bases was evaluated at different reaction temperatures and
reaction times. The use of t-BuOK and n-butyllithium re-
sulted in complex mixtures, whereas LDA did not convert
the starting material completely. Sodium hydride was se-
lected as the most suitable base, although it was difficult
to drive the reaction to completion. Use of only 1.1 equiv-
alents of sodium hydride at room temperature led to in-
complete conversion. Use of a larger excess of sodium
hydride (1.5 equiv) at room temperature for 16 hours, fol-
lowed by a certain period of reflux (1–3 h) resulted in the
complete conversion of the starting material. Small
amounts of succinimide, still present in the reaction mix-
ture after workup of the a-chlorination step (supported by
In the context of our continuing interest in agrochemical
applications,9 our attention is focussed on the develop-
ment of new strategies for the synthesis of heterocyclic
aminophosphonates. In particular, the chemistry of aziri-
dines is appealing, because of the possibile ring opening
or cross-linking reactions of aziridines. This feature gives
these compounds antitumor potential and enzyme inhibi-
tor applications.10 This paper describes our efforts to-
wards the study of scantly investigated electron-poor
azadienes,11,12 e.g. 1-phosphono-2-aza-1,3-dienes, and
their reactivity towards aziridination.
SYNTHESIS 2004, No. 5, pp 0722–0734
x
x
.
x
x
.2
0
0
4
Advanced online publication: 24.02.2004
DOI: 10.1055/s-2004-815969; Art ID: Z18503SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis and Aziridination of 1-Phosphono-2-aza-1,3-dienes
723
Scheme 1 Synthesis of 1-phosphono-2-aza-1,3-dienes 14–17
1H NMR spectrum), was responsible for quenching of
some sodium hydride. An excess of 0.5 equivalent of so-
dium hydride was sufficient in all cases to drive the 1,4-
dehydrochlorination to completion. The concentration of
the starting material in THF is important for the course of
the reaction. A concentration exceeding 0.1 M of starting
material in THF leads to lower yields or even to the for-
mation of complex reaction mixtures. Since 1-phosphono-
2-aza-1,3-dienes 14–17 are quite sensitive to prolonged
heating, the end of the period of reflux has to be monitored
Table 1 Overall Yields for 1-Phosphono-2-aza-1,3-dienes 14–17
Product
14a
15a
16a
17a
14b
15b
16b
17b
14c
R1
R2
Yield (%)
83
H
CH3
C6H5
CH3
78
p-CH3OC6H4
p-BrC6H4
H
CH3
51
CH3
73
CH2CH3
CH2CH3
CH2CH3
CH2CH3
(CH2)5
(CH2)5
(CH2)5
(CH2)5
75
carefully, either by thin layer chromatography, or by 31
P
C6H5
74
NMR spectroscopy (the signal shifts from around 22 to 8–
9 ppm). After workup, the azadienes 14–17 were isolated
in moderate to good overall yield and satisfactory purity
(>90%) (Table 1).
p-CH3OC6H4
p-BrC6H4
H
65
70
Attempts were made to purify the crude reaction mixture
by flash chromatography, but this always led to a consid-
erable loss of product because of the high affinity of the
azadienes for silica gel. Therefore, the azadienes 14–17
were used as such for the evaluation of further conver-
sions.
80
15c
C6H5
72
16c
p-CH3OC6H4
p-BrC6H4
62
17c
80
After 1,4-dehydrochlorination, the formation of only one
in-plane isomer is observed. Considering the iminofunc-
tion in the azadienes 14–17, only the E-isomer is formed
as shown in Scheme 1. This conclusion is deduced from
NOE experiments performed on azadienes 14, 16 and 17.
The selective saturation of the signal of the proton at C-3
afforded a positive NOE for the proton on C-1 (in the case
of azadiene 14) as well as for the two ortho protons (rela-
tive to the substituent bearing the phosphonate moiety) of
the aromatic ring (in the case of azadienes 16 and 17)
(Figure 1). This conclusion is also supported by the large
heteronuclear coupling between carbon C-3 and phospho-
rus (3JC,P) in the azadienes 14 (3JC,P = 40.3 Hz) and 16–17
3
(3JC,P = 31.6–34.1 Hz). It was shown that the JC,P cou-
pling constant is considerably bigger in trans derivatives
(3JC,P = ca. 24 Hz) than in the corresponding cis deriva-
tives (3JC,P = 8–10 Hz).15
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

724
B. Vanderhoydonck, C. V. Stevens
PAPER
Following the reaction with 31P NMR spectroscopy, no
formation of a triazoline intermediate (via a 1,3-dipolar
addition), which subsequently loses nitrogen, was ob-
served. After evaporating the solvent and the excess of di-
azomethane, 2-phosphonoaziridines 18a–c were isolated
in good to excellent yield in sufficient purity (>95%)
(Equation 1). Analytically pure compounds could be ob-
tained by flash chromatography, although a considerable
loss of product was noticed.
R3
R2
4
R3
R2
H
4
2
N
1
H
3
2
N
1
3
EtO
EtO
EtO
EtO
P
6% NOE
P
H
O
O
H
X
7% NOE
14
16 (X = OCH3)
17 (X = Br)
Figure 1 NOE enhancements observed for 14, 16 and 17
Although azadienes 14a–c reacted most readily with dia-
zomethane yielding the corresponding aziridines 18a–c,
the azadienes 15–17 did not react at all and the starting
material was recovered. An explanation for this complete
loss of reactivity could be the extended conjugation be-
tween the azadiene and the aromatic ring, causing an in-
creased electronic stability of the azadienes 15–17. This
enhanced stability can explain the resistance of azadienes
15–17 towards nucleophilic addition of diazomethane at
the imino function.
To our knowledge, 1-phosphono-2-aza-1,3-dienes 14–15
are only mentioned twice in literature, e.g. in a prelimi-
nary communcation by our group9 and by a Russian re-
search team, which described a 1,5-hydrogen shift from
the methyl group to the imidoyl carbon upon treatment
with base.11
Reactivity Study of 1-Phosphono-2-aza-1,3-dienes
and the Synthesis of 2-Phosphonoaziridines
Synthesis of 2-Ethoxycarbonyl-3-phosphonoaziri-
dines and 2-Phosphono-3-(trimethylsilyl)aziridines
Because of the lack of information concerning the reactiv-
ity of 1-phosphono-2-aza-1,3-dienes, a study was per-
formed in order to evaluate the scope of the reactivity of
this new class of compounds. Since the reactivity of aza-
dienes 14–17 could be rationalized as an enamine or as an
imine, nucleophilic as well as electrophilic reagents were
evaluated. Reactions with different nucleophiles (cyanide,
methoxide, azide, phosphite, Grignard reagent) did not
lead to the expected adducts to the imine function, but re-
sulted in complex reaction mixtures. Similary, the reac-
tion of some electrophilic reagents (bromine, cyanogen
bromide) also led to complex reaction mixtures. There-
fore, the reactivity pattern of the azadienes cannot be split
in an imine or an enamine reactivity.
To evaluate the generality of the reaction pattern of aza-
dienes 14–17 towards diazo compounds, their reactions
with ethyl diazoacetate (EDA) and (trimethylsilyl)diazo-
methane were examined. Although azadienes 14a–c react
easily with diazomethane at room temperature, no reac-
tion was observed with EDA. Therefore, the effects of
several catalysts [Cu(OTf)2, Yb(OTf)3, Nd(OTf)3] were
evaluated.
Using Cu(OTf)2 as a catalyst with the aim to form tran-
sient metal carbene species, the conversion was not suc-
cessful, neither if EDA was added at once or over a period
of five hours. Starting material or a trace of aziridine 19
(<10%) was isolated, respectively. Since both reaction
conditions afforded diethyl maleate and diethyl fumarate
as the main side products, azadienes 14a–c seem not to be
susceptible to the aziridination reactions.
However, reaction of azadienes 14a–c with an excess of
diazomethane (approximately 5 equivalents generated
from N-methyl-N-nitroso-p-toluenesulfonamide and po-
tassium hydroxide) in diethyl ether led to the fast forma-
tion of the corresponding 2-phosphonoaziridines 18a–c.
(Equation 1). The regiospecific addition of diazomethane
to azadienes 14a–c is directed by the electron-withdraw-
ing phosphonate group resulting in the attack of diaz-
omethane at the electrophilic imino carbon.
Therefore, the Lewis acid-catalyzed activation of the imi-
ne function was evaluated, followed by a nucleophilic ad-
dition of EDA.16,17 Since lanthanide triflates were recently
reported as effective Lewis acid catalysts for the synthesis
of aziridines,18 Yb(OTf)3 and Nd(OTf)3 were selected as
Lewis acid. The aziridination of azadiene 14a was first
evaluated in different solvents (THF, ethanol and dichlo-
romethane) with Yb(OTf)3 as a catalyst. From these ex-
periments, dichloromethane was selected as the most
suitable solvent. The crude reaction mixture contained the
cis- as well as the trans-isomer of aziridines 19a–c in a ra-
H
H
R3
R2
OEt
OEt
5 equiv. CH2N2
Et2O
N
OEt
OEt
N
P
R2
P
R3
O
H
O
14a. R2 = R3 = CH3
18a. R2 = R3 = CH3
93% (57%)
14b. R2 = R3 = CH2CH3
14c. R2 = R3 = (CH2)5
18b. R2 = R3 = CH2CH3 68% (30%)
18c. R2 = R3 = (CH2)5 72% (29%)
1
tio of 85:15 (cis/trans) (calculated from the H NMR
spectrum). By means of flash chromatography, only the
cis-isomer could be isolated and fully characterized
(Scheme 2). Applying these reaction conditions with
Nd(OTf)3 instead, the reaction was equally successful in
view of the yield, but the reaction took twice as long. Fur-
Equation 1 Synthesis of 2-phosphono-1-vinylaziridines 18a–c (the
yield in parentheses are those after purification by flash chromatogra-
phy).
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

PAPER
Synthesis and Aziridination of 1-Phosphono-2-aza-1,3-dienes
725
COOEt
R3
1.1 equiv. N2CHCOOEt
N
OEt
OEt
0.1 equiv. Yb(OTf)3
R2
P
H
O
19a. R2 = R3 = CH3
(40%)
H
H
19b. R2 = R3 = CH2CH3 (45%)
19c. R2 = R3 = (CH2)5 (43%)
R2
OEt
OEt
N
P
R3
O
14a. R2 = R3 = CH3
14b. R2 = R3 = CH2CH3
14c. R2 = R3 = (CH2)5
TMS
R3
1.5 equiv. N2CHTMS
toluene
N
OEt
OEt
R2
P
H
O
20a. R2 = R3 = CH3
20b. R2 = R3 = CH2CH3 (42%)
20c. R2 = R3 = (CH2)5
(44%)
(30%
)
Scheme 2 Synthesis of 2-ethoxycarbonyl-3-phosphonoaziridines 19a–c and 2-phosphono-3-(trimethylsilyl)aziridines 20a–c (The yield in
parentheses are those obtained after flash chromatography).
Flash chromatography was performed on silica gel (Acros, 0.035–
0.070 mm). 1H NMR spectra were recorded at 270 MHz on a Jeol
JNM EX270 FT-NMR instrument. 13C NMR and 31P NMR experi-
ments were acquired at 68 MHz and 109 MHz, respectively. The
relative proportions between two diastereoisomers were measured
by integration of the 1H peaks. Chemical shifts (d) are reported in
ppm from TMS as an internal reference. Coupling constants (J) are
given in Hertz. IR-spectra were recorded with a Perkin-Elmer Spec-
trum One FT-IR spectrometer. Low-resolution mass spectra (MS)
were obtained at 70eV on a Varian MAT 112 spectrometer. All sol-
vents were dried extensively over sodium/benzophenone ketyl
(Et2O, THF) or CaH2 (CH2Cl2). Petroleum ether used had bp 40–60
°C. The 1,4-dehydrochlorination experiments as well as the azirid-
ination reactions were performed under N2.
thermore, the ratio of the cis- and the trans-isomer is ap-
proximately the same, e.g. 88:12 (cis/trans).
In order to obtain 2-phosphono-3-(trimethylsilyl)aziri-
dines 20a–c, azadienes 14a–c were treated with (trimeth-
ylsilyl)diazomethane under different reaction conditions.
At room temperature using different solvents (dichlo-
romethane, THF, toluene), the reaction led to the isolation
of starting material when performed in the absence as well
as in the presence of Yb(OTf)3. Using AgSbF6 as a cata-
lyst in THF at –78 °C instead, a complex reaction mixture
was obtained after workup. Refluxing azadienes 14a–c in
the presence of 1.5 equivalents of (trimethylsilyl)diazo-
methane in toluene for 48 hours generated 2-phosphono-
3-(trimethylsilyl)aziridines 20a–c in moderate yields
(Scheme 2). The crude reaction mixtures contained only
the cis-isomer and were purified by flash chromatogra-
phy. Similarly to the lack of reactivity of azadienes 15–17
towards diazomethane, these azadienes with aromatic
substituents neither react with EDA nor with (trimethyl-
silyl)diazomethane under the evaluated reaction condi-
tions.
Diethyl 1-Amino-1-arylmethylphosphonates 3–5; General Pro-
cedure
To a solution of the corresponding aldehyde (26 mmol), NH4OAc
(4.0 g, 52 mmol), diethyl phosphite (3.6 g, 26 mmol) and LiClO4
(277 mg, 2.6 mmol) in EtOH (220 mL) in a 500 mL flask, were add-
ed anhydrous molecular sieves (4 Å, 2.5 g). The reaction mixture
was protected from moisture by a CaCl2 tube on top of the condens-
er and was heated under reflux for 5 d. The mixture was cooled to
r.t. and was filtered over Celite. The solution was extracted with aq
2 M HCl and CH2Cl2 after which the aqueous fraction was made al-
kaline with solid NaOH. Subsequently, the aqueous fraction was ex-
tracted with CH2Cl2 and the organic fraction was dried (MgSO4).
After filtration, the solvent was removed under reduced pressure af-
fording the crude amino phosphonate 3–5 in 30–50% yields as yel-
lowish oils (purity >90%).
Conclusion
To conclude, the chemistry of 1-phosphono-2-aza-1,3-
dienes 14–17 has been evaluated and a direct synthesis of
2-phosphonoaziridines 18a–c has been developed. Aza-
dienes 14a–c can also be transformed into the correspond-
ing 2-ethoxycarbonyl-3-phosphonoaziridines 19a–c and
2-phosphono-3-(trimethylsilyl)aziridines 20a–c using
ethyl diazoacetate (EDA) and (trimethylsilyl)diazo-
methane, respectively. 1-Phosphono-2-aza-1,3-dienes
14–17 and the electron-deficient aziridines 18a–c, 19a–c
and 20a–c seem interesting building blocks for highly
functionalized acyclic and cyclic a-aminophosphonates.
The chemistry of both classes of compounds will be fur-
ther developed for the synthesis of azaphosphonates with
potential applications in agrochemistry.
Diethyl Amino(phenyl)methylphosphonate (3)
Synthesized according to the general procedure with benzaldehyde;
Yield: 3.16 g (50%); yellowish oil. After distillation the yield
dropped to 30%; bp 93–95 °C/0.01 mmHg.
IR (neat): 3374, 3295, 1602, 1241, 1053, 1027 cm–1.
1H NMR (CDCl3): d = 1.18 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.28 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.84 (2 H, s, NH2), 4.05 [4
H, m, P(O)OCH2CH3], 4.26 (1 H, d, JH,P = 17.2 Hz, CHP), 7.35 (3
H, m, CH), 7.47 (2 H, m, CH).
13C NMR (CDCl3): d = 16.57 [2 C, t, JC,P = 6.7 Hz, P(O)OCH2CH3],
54.22 (d, JC,P = 150.1 Hz, CHP), 62.88 [2 C, t, JC,P = 7.9 Hz,
P(O)OCH2CH3], 127.83 (CH), 127.92 (2 CH), 128.59 (2 CH),
137.91 (Cquat).
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

726
B. Vanderhoydonck, C. V. Stevens
PAPER
31P NMR (CDCl3): d = 25.24.
MS: m/z = 243 (2, [M+]), 242 (3), 185 (2), 133 (29), 107 (44), 106
(100), 104 (34), 84 (18), 81 (21), 79 (56), 77 (54), 65 (19), 51 (17),
47 (12).
13C NMR (CDCl3):
P(O)OCH2CH3], 19.03 (2 CH3), 34.34 (CH), 57.00 (d, JC,P = 155.7
Hz, NCH2P), 62.35 [2 C, d, JC,P = 6.1 Hz, P(O)OCH2CH3], 175.06
(d, JC,P = 14.3 Hz, C=N).
d
=
16.47 [2 C, d, JC,P = 6.1 Hz,
31P NMR (CDCl3): d = 23.06.
Diethyl Amino(4-methoxyphenyl)methylphosphonate (4)
Synthesized according to the general procedure with 4-methoxy-
benzaldehyde; yield: 3.55 g (50%); yellowish oil.
MS: m/z = 178 (4), 152 (57), 125 (100), 108 (36), 97 (50), 84 (45),
80 (20), 65 (13), 55 (23).
IR (neat): 3379, 3295, 1610, 1248, 1053, 1027 cm–1.
Diethyl {[(E)-2-Ethyl-1-butylidene]amino}methylphosphonate
(6b)
1H NMR (CDCl3): d = 1.19 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.28 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.83 (2 H, s, NH2), 3.81 (3
H, s, OCH3), 4.03 [4 H, m, P(O)OCH2CH3], 4.21 (1 H, d, JH,P = 16.2
Hz, CHP), 6.89 (2 H, d, J = 8.6 Hz, CH), 7.38 (2 H, dd, J = 8.9, 2.3
Hz, CH).
Synthesized according to the general procedure with diethyl ami-
nomethylphosphonate (2) and aldehyde 1b; yield: 1.21 g (97%);
yellowish oil.
IR (neat): 1663 cm–1.
13C NMR (CDCl3): d = 16.44 [2 C, t, JC,P = 6.1 Hz, P(O)OCH2CH3],
53.39 (d, JC,P = 151.4 Hz, CHP), 55.25 (OCH3), 62.62 [d, JC,P = 7.3
Hz, P(O)OCH2CH3], 62.78 [d, JC,P = 7.3 Hz, P(O)OCH2CH3],
113.87 (2 C, d, JC,P = 2.4 Hz, CH), 128.86 (2 C, d, JC,P = 6.1 Hz,
CH), 129.66 (d, JC,P = 3.6 Hz, Cquat), 159.26 (d, JC,P = 2.4 Hz, Cquat).
31P NMR (CDCl3): d = 25.50.
MS: m/z = 273 (8, [M+]), 229 (3), 175 (4), 164 (13), 137 (36), 136
(100), 135 (16), 134 (26), 121 (11), 109 (23), 91 (19), 83 (11), 65
(10), 43 (4).
1H NMR (CDCl3): d = 0.90 (6 H, t, J = 7.4 Hz, CH3), 1.33 [6 H, t,
J = 7.1 Hz, P(O)OCH2CH3], 1.49 (4 H, quint, J = 7.5 Hz, CH2), 2.12
(1 H, q, J = 6.6 Hz, CH), 3.88 (2 H, d, JH,P = 17.2 Hz, NCH2P), 4.16
[4 H, m, P(O)OCH2CH3], 7.49 (1 H, d, J = 5.1 Hz, HC=N).
13C NMR (CDCl3): d = 11.54 (2 CH3), 16.47 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 24.87 (2 CH2), 48.54 (d, JC,P = 2.4 Hz, CH), 57.09
(d, JC,P = 153.8 Hz, NCH2P), 62.26 [2 C, d, JC,P = 7.3 Hz,
P(O)OCH2CH3], 174.58 (d, JC,P = 15.9 Hz, C=N).
31P NMR (CDCl3): d = 23.17.
MS: m/z = 152 (67), 125 (100), 108 (35), 97 (42), 83 (29), 65 (23),
55 (27), 41 (31).
Diethyl Amino(4-bromophenyl)methylphosphonate (5)
Synthesized according to the general procedure with 4-bromoben-
zaldehyde; yield: 2.51 g (30%); yellowish oil.
IR (neat): 3377, 3296, 1590, 1487, 1240, 1026 cm–1.
Diethyl {[(E)-Cyclohexylmethylidene]amino}methylphosphon-
ate (6c)
Synthesized according to the general procedure with diethyl ami-
nomethylphosphonate (2) and aldehyde 1c; yield: 1.28 g (98%);
yellowish oil.
IR (neat): 1659 cm–1.
1H NMR (CDCl3): d = 1.22 [3 H, t, J = 7.3 Hz, P(O)OCH2CH3],
1.28 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.80 (2 H, s, NH2), 4.07 [4
H, m, P(O)OCH2CH3], 4.24 (1 H, d, JH,P = 17.2 Hz, CHP), 7.34 (2
H, dd, J = 8.4, 2.1 Hz, CH), 7.49 (2 H, d, J = 7.9 Hz, CH).
13C NMR (CDCl3): d = 16.42 [2 C, t, JC,P = 5.5 Hz, P(O)OCH2CH3],
53.56 (d, JC,P = 150.2 Hz, CHP), 62.87 [2 C, t, JC,P = 6.7 Hz,
P(O)OCH2CH3], 121.77 (d, JC,P = 3.6 Hz, Cquat), 129.45 (2 C, d,
1H NMR (CDCl3): d = 1.27–1.35 (6 H, m, CH2CH2CH2), 1.34 [6 H,
t, J = 7.1 Hz, P(O)OCH2CH3], 1.64–1.84 (4 H, m, 2 CH2), 2.25 (1
H, m, CH), 3.85 (2 H, d, JH,P = 17.2 Hz, NCH2P), 4.16 [4 H, m,
P(O)OCH2CH3], 7.58 (1 H, t, JH,P = 4.8 Hz, HC=N).
JC,P = 6.1 Hz, CH), 131.52 (2 C, d, JC,P = 2.4 Hz, CH), 136.84 (d,
J = 3.7 Hz, Cquat).
31P NMR (CDCl3): d = 24.27.
MS: m/z = 323/321 (2/1, [M+]), 265 (2), 263 (2), 186 (84), 185 (23),
184 (100), 183 (24), 111 (21), 83 (14), 77 (14).
13C NMR (CDCl3): d = 16.38 [2 C, d, JCP = 6.1 Hz, P(O)OCH2CH3],
25.22 (2 CH2), 25.89 (CH2), 29.23 (2 CH2), 43.40 (CH), 57.09 (d,
JC,P = 153.7 Hz, NCH2P), 62.15 [2 C, d, JC,P = 7.3 Hz,
P(O)OCH2CH3], 174.82 (d, JC,P = 14.6 Hz, C=N).
31P NMR (CDCl3): d = 23.13.
MS: m/z = 261 (1, [M+]), 206 (6), 193 (19), 152 (74), 125 (100), 108
Diethyl [(Alkylidene)amino]methylphosphonates 6–9; General
Procedure
(35), 97 (31), 95 (22), 83 (15), 55 (12), 41 (19).
To a solution of the appropriate diethyl aminomethylphosphonate
2–5 (5 mmol) and aldehyde 1 (5 mmol) in CH2Cl2 (10 mL) in a 50
mL flask, was added anhyd MgSO4 (0.30 g). The reaction mixture
was protected from moisture by a CaCl2 tube on top of the condens-
er and was heated under reflux for 3 h. The mixture was then cooled
to r.t. and the MgSO4 was filtered off. The solvent was removed un-
der reduced pressure to afford the imines 6–9 in 93–98% yields as
yellowish oils with a purity of >95%.
Diethyl {[(E)-2-Methyl-1-propylidene]amino}(phenyl)methyl-
phosphonate (7a)
Synthesized according to the general procedure with diethyl ami-
no(phenyl)methylphosphonate (3) and aldehyde 1a; yield: 1.46 g
(98%); yellowish oil.
IR (neat): 1663 cm–1.
1H NMR (CDCl3): d = 1.11 (3 H, d, J = 7.9 Hz, CH3), 1.12 (3 H, d,
J = 7.1 Hz, CH3), 1.22 [6 H, m, P(O)OCH2CH3], 2.57 (1 H, m, CH),
4.01 [4 H, m, P(O)OCH2CH3], 4.66 (1 H, d, JH,P = 18.1 Hz, NCHP),
7.31 (3 H, m, CH), 7.55 (2 H, m, CH), 7.71 (1 H, t, JH,P = 4.8 Hz,
HC=N).
13C NMR (CDCl3): d = 16.26 [JC,P = 4.9 Hz, P(O)OCH2CH3], 16.30
[JC,P = 4.9 Hz, P(O)OCH2CH3], 18.99 (2 CH3), 34.30 (CH), 62.84
[2 C, t, JC,P = 7.9 Hz, P(O)OCH2CH3], 73.13 (d, JC,P = 152.6 Hz,
NCHP), 127.48 (d, JC,P = 3.7 Hz, CH), 128.21 (2 CH), 128.30
(2 CH), 136.35 (d, JC,P = 7.3 Hz, Cquat), 173.41 (d, JC,P = 15.9 Hz,
C=N).
Diethyl {[(E)-2-Methyl-1-propylidene]amino}methylphosphon-
ate (6a)
Synthesized according to the general procedure with diethyl ami-
nomethylphosphonate (2) and aldehyde 1a; yield: 1.08 g (98%);
yellowish oil.
IR (neat): 1670, 1250 cm–1.
1H NMR (CDCl3): d = 1.09 (6 H, t, J = 6.9 Hz, CH3), 1.34 [6 H, t,
J = 6.9 Hz, P(O)OCH2CH3], 2.51 (1 H, m, CH), 3.85 (2 H, d,
JH,P = 17.2 Hz, NCH2P), 4.16 [4 H, m, P(O)OCH2CH3], 7.61 (1 H,
t, J = 4.6 Hz, HC=N).
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

PAPER
Synthesis and Aziridination of 1-Phosphono-2-aza-1,3-dienes
727
31P NMR (CDCl3): d = 20.73.
MS: m/z = 297 (1, [M+]), 265 (2), 229 (10), 228 (83), 172 (21), 161
NCHP), 112.74 (2 CH), 127.44 (d, JC,P = 7.3 Hz, Cquat), 128.54 (2 C,
d, JC,P = 6.1 Hz, CH), 158.21 (d, JC,P = 3.7 Hz, COCH3), 172.10 (d,
JC,P = 15.9 Hz, C=N).
(14), 160 (100), 134 (6), 91 (5).
31P NMR (CDCl3): d = 20.84.
Diethyl {[(E)-2-Ethyl-1-butylidene]amino}(phenyl)methylphos-
phonate (7b)
Synthesized according to the general procedure with diethyl ami-
no(phenyl)methylphosphonate (3) and aldehyde 1b; yield: 1.58 g
(97%); yellowish oil.
MS: m/z = 327 (2, [M+]), 258 (15), 191 (14), 190 (100), 175 (6), 134
(10), 121 (19), 111 (9), 91 (87), 85 (17), 65 (10), 57 (11), 55 (9), 40
(12).
Diethyl {[(E)-2-Ethyl-1-butylidene]amino}(4-methoxyphenyl)-
methylphosphonate (8b)
IR (neat): 1662 cm–1.
Synthesized according to the general procedure with diethyl ami-
no(4-methoxyphenyl)methylphosphonate (4) and aldehyde 1b;
yield: 1.74 g (98%); yellowish oil.
IR (neat): 1661, 1610 cm–1.
1H NMR (CDCl3): d = 0.84 (3 H, t, J = 7.1 Hz, CH3), 0.95 (3 H, t,
J = 7.1 Hz, CH3), 1.20 [3 H, t, J = 7.4 Hz, P(O)OCH2CH3], 1.24 [3
H, t, J = 7.4 Hz, P(O)OCH2CH3], 1.51 (4 H, m, CH2), 2.22 (1 H, q,
J = 7.6 Hz, CH), 4.01 [4 H, m, P(O)OCH2CH3], 4.68 (1 H, d,
J
H,P = 17.8 Hz, NCHP), 7.32 (3 H, m, CH), 7.57 (3 H, m, CH,
1H NMR (CDCl3): d = 0.84 (3 H, t, J = 7.4 Hz, CH3), 0.94 (3 H, t,
J = 7.4 Hz, CH3), 1.23 [6 H, q, J = 6.9 Hz, P(O)OCH2CH3], 1.51 (4
H, m, CH2), 2.20 (1 H, sextet, J = 6.6 Hz, CH), 3.80 (3 H, s, OCH3),
4.01 [4 H, m, P(O)OCH2CH3], 4.63 (1 H, d, JH,P = 17.1 Hz, NCHP),
6.88 (2 H, d, J = 8.6 Hz, CH), 7.46 (2 H, dd, J = 8.6 Hz, JH,P = 2.3
Hz, CH), 7.56 (1 H, dd, J = 6.6 Hz, JH,P = 4.6 Hz, HC=N).
HC=N).
13C NMR (CDCl3): d = 10.51 (CH3), 10.62 (CH3), 15.38 [2 C, d,
JC,P = 4.9 Hz, P(O)OCH2CH3], 23.88 (2 CH2), 47.39 (CH), 61.74 [2
C, t, JC,P = 6.1 Hz, P(O)OCH2CH3], 72.44 (d, JC,P = 152.6 Hz,
NCHP), 126.56 (CH), 127.30 (4 CH), 135.60 (d, JC,P = 7.3 Hz,
C
quat), 171.72 (d, JC,P = 15.8 Hz, C=N).
13C NMR (CDCl3): d = 11.52 (CH3), 11.63 (CH3), 16.40 [d,
JC,P = 6.1 Hz, P(O)OCH2CH3], 16.44 [d, JC,P = 4.9 Hz,
31P NMR (CDCl3): d = 20.71.
P(O)OCH2CH3], 24.89 (2 CH2), 48.35 (CH), 55.06 (s, OCH3),
62.69 [2 C, t, JC,P = 7.9 Hz, P(O)OCH2CH3], 72.71 (d, JC,P = 155.0
Hz, NCHP), 113.67 (2 CH), 128.49 (d, JC,P = 8.5 Hz, Cquat), 129.42
(2 C, d, JC,P = 6.1 Hz, CH), 159.13 (d, JC,P = 2.5 Hz, COCH3),
172.55 (d, JC,P = 15.8 Hz, C=N).
MS: m/z = 325 (1, [M+]), 296 (3), 268 (10), 229 (18), 228 (100), 200
(18), 189 (22), 188 (92), 172 (42), 160 (26), 134 (39), 118 (16), 106
(33), 91 (27), 81 (6).
Diethyl {[(E)-Cyclohexylmethylidene]amino}(phenyl)methyl-
phosphonate (7c)
31P NMR (CDCl3): d = 21.07.
Synthesized according to the general procedure with diethyl ami-
no(phenyl)methylphosphonate (3) and aldehyde 1c; yield: 1.62 g
(96%); yellowish oil.
MS: m/z = 355 (0.2, [M+]), 299 (2), 265 (2), 258 (36) 219 (17), 218
(100) 190 (5), 136 (24), 121 (20), 111 (8), 40 (32).
IR (neat): 1662 cm–1.
Diethyl {[(E)-Cyclohexylmethylidene]amino}(4-methoxyphen-
yl)methylphosphonate (8c)
Synthesized according to the general procedure with diethyl ami-
no(4-methoxyphenyl)methylphosphonate (4) and aldehyde 1c;
yield: 1.78 g (97%); yellowish oil.
1H NMR (CDCl3): d = 1.17–1.47 [12 H, m, 3 CH2, P(O)OCH2CH3],
1.64–1.90 (4 H, m, 2 CH2), 2.30 (1 H, m, CH), 4.03 [4 H, m,
P(O)OCH2CH3], 4.65 (1 H, d, JH,P = 18.1 Hz, NCHP), 7.33 (3 H, m,
CH), 7.53 (1 H, m, CH), 7.68 (1 H, t, JH,P = 4.9 Hz, HC=N).
IR (neat): 1661, 1610 cm–1.
13C NMR (CDCl3):
d = 16.65 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 25.62 (2 CH2), 26.29 (CH2), 29.69 (2 CH2), 43.90
(CH), 63.22 [2 C, t, JC,P = 7.9 Hz, P(O)OCH2CH3], 73.57 (d,
JC,P = 152.6 Hz, NCHP), 127.81 (d, JC,P = 3.6 Hz, CH), 128.54 (2 C,
d, JC,P = 3.7 Hz, CH), 128.64 (2 CH), 136.74 (d, JC,P = 8.6 Hz,
Cquat), 173.02 (d, JC,P = 14.6 Hz, C=N).
1H NMR (CDCl3): d = 1.17–1.38 [12 H, m, 3 CH2, P(O)OCH2CH3],
1.65–1.91 (4 H, m, 2 CH2), 2.30 (1 H, m, CH), 3.79 (3 H, s, OCH3),
4.02 [4 H, m, P(O)OCH2CH3], 4.60 (1 H, d, JH,P = 17.5 Hz, NCHP),
6.88 (2 H, d, J = 8.6 Hz, CH), 7.45 (2 H, dd, J = 8.6 Hz, JH,P = 2.0
Hz, CH), 7.66 (1 H, t, J = 4.8 Hz, HC=N).
31P NMR (CDCl3): d = 20.77.
MS: m/z = 337 (0.3, [M+]), 269 (12), 229 (11), 228 (86), 200 (100),
200 (18), 172 (19), 160 (12), 132 (9), 118 (14), 106 (48), 95 (17), 91
(42), 65 (10), 40 (14).
13C NMR (CDCl3): d = 15.42 [2 C, t, JC,P = 4.3 Hz, P(O)OCH2CH3],
24.39 (2 CH2), 25.00 (d, J = 8.5 Hz, CH2), 28.41 (2 CH2), 42.55
(CH), 54.03 (OCH3), 61.78 [2 C, t, JC,P = 8.5 Hz, P(O)OCH2CH3],
71.55 (d, JC,P = 153.8 Hz, NCHP), 112.63 (2 CH), 127.40 (d,
JC,P = 7.3 Hz, Cquat), 128.45 (2 C, d, JC,P = 5.9 Hz, CH), 158.13 (d,
JC,P = 2.5 Hz, COCH3), 171.27 (d, JC,P = 14.6 Hz, C=N).
31P NMR (CDCl3): d = 20.94.
Diethyl (4-Methoxyphenyl){[(E)-2-methyl-1-propylidene]ami-
no}methylphosphonate (8a)
Synthesized according to the general procedure with diethyl ami-
no(4-methoxyphenyl)methylphosphonate (4) and aldehyde 1a;
yield: 1.60 g (98%); yellowish oil.
MS: m/z = 367 (0.5, [M+]), 258 (15), 230 (100), 202 (21) 164 (15),
136 (91), 134 (22), 121 (69), 95 (24), 77 (14), 57 (50), 41 (29).
IR (neat): 1662, 1610 cm–1.
Diethyl (4-Bromophenyl){[(E)-2-methyl-1-propylidene]ami-
no}methylphosphonate (9a)
Synthesized according to the general procedure with diethyl ami-
no(4-bromophenyl)methylphosphonate (5) and aldehyde 1a; yield:
1.86 g (99%); yellowish oil.
1H NMR (CDCl3): d = 1.09 (3 H, d, J = 6.6 Hz, CH3), 1.11 (3 H, d,
J = 6.9 Hz, CH3), 1.22 [3 H, t, J = 6.9 Hz, P(O)OCH2CH3], 1.24 [3
H, t, J = 6.9 Hz, P(O)OCH2CH3], 2.56 (1 H, m, CH), 3.80 (3 H, s,
OCH3), 4.03 [4 H, m, P(O)OCH2CH3], 4.61 (1 H, d, JH,P = 17.5 Hz,
NCHP), 6.89 (2 H, d, J = 8.9 Hz, CH), 7.45 (2 H, dd, J = 8.9 Hz,
IR (neat): 1663 cm–1.
J
H,P = 2.3 Hz, CH), 7.68 (1 H, t, JH,P = 4.8 Hz, HC=N).
1H NMR (CDCl3): d = 1.10 (3 H, d, J = 6.9 Hz, CH3), 1.12 (3 H, d,
J = 6.9 Hz, CH3), 1.22 [3 H, t, J = 6.9 Hz, P(O)OCH2CH3], 1.25 [3
H, t, J = 7.3 Hz, P(O)OCH2CH3], 2.57 (1 H, m, CH), 4.03 [4 H, m,
13C NMR (CDCl3):
P(O)OCH2CH39, 18.11 (2 CH3), 33.37 (CH), 54.12 (OCH3), 61.83
[2 C, t, JC,P = 7.9 Hz, P(O)OCH2CH3], 71.50 (d, JC,P = 153.8 Hz,
d
=
15.47 [2 C, t, JC,P = 4.9 Hz,
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

728
B. Vanderhoydonck, C. V. Stevens
PAPER
P(O)OCH2CH3], 4.60 (1 H, d, JH,P = 18.1 Hz, NCHP), 7.44 (4 H, m,
CH), 7.71 (1 H, t, J = 4.6 Hz, HC=N).
chlorosuccinimide (690 mg, 5.2 mmol, 1.05 equiv) was added. The
reaction mixture was protected from moisture by a CaCl2 tube on
top of the condenser and was heated under reflux for 1 h. The mix-
ture was cooled for 2 h at –18 °C and the succinimide was filtered.
Evaporation of the solvent under vacuum led to the isolation of imi-
ne 10–13 as yellowish oils in good yields (90–98%) and with a pu-
rity of >90% (except for imines 11a, 12a and 13a which were less
pure).
13C NMR (CDCl3):
P(O)OCH2CH3], 18.97 (2 CH3), 34.32 (CH), 62.91 [2 C, t, JC,P = 7.3
Hz, P(O)OCH2CH3], 72.36 (d, JC,P = 151.4 Hz, NCHP), 121.37 (d,
d = 16.38 [2 C, d, JC,P = 3.7 Hz,
JC,P = 3.7 Hz, CBr), 130.03 (2 C, d, JC,P = 6.1 Hz, CH), 131.23
(2 CH), 135.72 (d, JC,P = 7.3 Hz, Cquat), 173.65 (d, JC,P = 14.6 Hz,
C=N).
31P NMR (CDCl3): d = 19.64.
MS: m/z = 377/375 (2/3, [M+]), 353 (8), 351 (5), 308 (55), 306 (54),
280 (12), 278 (12), 252 (15), 250 (14), 240 (95), 238 (100), 186
(26), 184 (33), 171 (22), 169 (21), 89 (19), 55 (25), 43 (11).
Diethyl {[(E)-2-Chloro-2-methyl-1-propylidene]amino}meth-
ylphosphonate (10a)
Synthesized according to the general procedure with imine 6a;
yield: 1.22 g (95%); yellowish oil. After distillation the yield
dropped to 50%; bp 93 °C/0.01 mmHg).
IR (neat): 1662 cm–1.
Diethyl (4-Bromophenyl){[(E)-2-ethyl-1-butylidene]amino}me-
thylphosphonate (9b)
Synthesized according to the general procedure with diethyl ami-
no(4-bromophenyl)methylphosphonate (5) and aldehyde 1b; yield:
1.98 g (98%); yellowish oil.
1H NMR (CDCl3): d = 1.34 [6 H, t, J = 7.3 Hz, P(O)OCH2CH3],
1.71 (6 H, s, CH3), 3.94 (2 H, dd, JH,P = 17.5 Hz, NCH2P), 4.16 [4
H, dq, J = 6.9, 7.3 Hz, P(O)OCH2CH3], 7.76 (1 H, d, JH,P = 4.9 Hz,
HC=N).
13C NMR (CDCl3): d = 16.45 [2 C, d, JCP = 6.8 Hz, P(O)OCH2CH3],
29.09 (CH3), 29.61 (CH3), 56.06 (d, JC,P = 154.4 Hz, NCH2P),
62.62 [2 C, d, JC,P = 6.1 Hz, P(O)OCH2CH3], 67.74 (CCl), 169.79
(d, JC,P = 16.6 Hz, C=N).
IR (neat): 1661 cm–1.
1H NMR (CDCl3): d = 0.84 (3 H, t, J = 7.4 Hz, CH3), 0.94 (3 H, t,
J = 7.4 Hz, CH3), 1.22 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.26 [3
H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.51 (4 H, m, CH2), 2.21 (1 H,
sextet, J = 6.5 Hz, CH), 4.02 [4 H, m, P(O)OCH2CH3], 4.62 (1 H, d,
JH,P = 18.1 Hz, NCHP), 7.45 (4 H, m, CH), 7.59 (1 H, dd, J = 6.3
Hz, JH,P = 4.6 Hz, HC=N)
31P NMR (CDCl3): d = 21.64.
MS: m/z = 219/220 (30), 178 (13), 152 (69), 125 (100), 108 (40), 97
(46), 82 (39), 65 (25).
13C NMR (CDCl3): d = 11.50 (CH3), 11.57 (CH3), 16.39 [2 C, d,
J
C,P = 4.9 Hz, P(O)OCH2CH3], 24.81 (2 CH2), 48.37 (CH), 62.91 [2
Diethyl {[(E)-2-Chloro-2-ethyl-1-butylidene]amino}meth-
ylphosphonate (10b)
Synthesized according to the general procedure with imine 6b;
yield: 1.36 g (96%); yellowish oil.
IR (neat): 1661 cm–1.
1H NMR (CDCl3): d = 0.99 (6 H, t, J = 7.4 Hz, CH3), 1.34 [6 H, t,
J = 7.1 Hz, P(O)OCH2CH3], 1.96 (4 H, m, CH2), 3.95 (2 H, d,
C, t, JC,P = 7.9 Hz, P(O)OCH2CH3], 72.69 (d, JC,P = 152.5 Hz,
NCHP), 121.46 (d, JC,P = 3.7 Hz, CBr), 129.92 (2 C, d, JC,P = 4.9
Hz, CH), 131.30 (2 CH), 135.70 (d, JC,P = 7.3 Hz, Cquat), 173.37 (d,
JC,P = 14.7 Hz, C=N).
31P NMR (CDCl3): d = 20.06.
MS: m/z = 405/403 (1/1, [M+]), 353 (6), 309 (97), 307 (100), 268
(80), 266 (82), 252 (30), 250 (31), 171 (38), 169 (38), 89 (17), 65
(10), 57 (11), 55 (18).
JH,P = 17.5 Hz, NCH2P), 4.16 [4 H, m, P(O)OCH2CH3], 7.68 (1 H,
d, JH,P = 5.0 Hz, HC=N).
Diethyl (4-Bromophenyl){[(E)-cyclohexylmethylidene]amino}-
methylphosphonate (9c)
Synthesized according to the general procedure with diethyl ami-
no(4-bromophenyl)methylphosphonate (5) and aldehyde 1c; yield:
2.04 g (98%); yellowish oil.
13C NMR (CDCl3): d = 8.70 (2 CH3), 16.44 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 31.86 (2 CH2), 56.34 (d, JC,P = 153.8 Hz, NCH2P),
62.51 [2 C, d, JC,P = 6.1 Hz, P(O)OCH2CH3], 76.84 (CCl), 169.99
(d, JC,P = 14.7 Hz, C=N).
31P NMR (CDCl3): d = 21.98.
IR (neat): 1661 cm–1.
MS: m/z = 281 (5), 247 (15), 232 (15), 152 (81), 150 (23), 125 (100),
110 (45), 108 (47), 97 (52), 84 (48), 51 (44), 49 (65).
1H NMR (CDCl3): d = 1.22 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.25 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.30–1.34 (6 H, m, CH2),
1.65–1.85 (4 H, m, CH2), 2.30 (1 H, m, CH), 4.02 [4 H, m,
P(O)OCH2CH3], 4.58 (1 H, d, JH,P = 18.5 Hz, NCHP), 7.44 (4 H, m,
CH), 7.68 (1 H, t, JH,P = 4.8 Hz, HC=N).
Diethyl {[(E)-(1-Chlorocyclohexyl)methylidene]amino}methyl-
phosphonate (10c)
Synthesized according to the general procedure with imine 6c;
yield: 1.41 g (95%); yellowish oil.
IR (neat): 1658 cm–1.
1H NMR (CDCl3): d = 1.33 [6 H, t, J = 6.9 Hz, P(O)OCH2CH3],
1.31–1.74 (6 H, m, CH2), 1.91–1.97 (4 H, m, CH2), 3.95 (2 H, d,
13C NMR (CDCl3):
P(O)OCH2CH3], 25.30 (2 CH2), 25.98 (CH2), 29.31 (2 CH2), 43.52
(CH), 62.95 [2 C, t, JC,P = 7.9 Hz, P(O)OCH2CH3], 72.48 (d,
d = 16.38 [2 C, d, JC,P = 6.1 Hz,
JC,P = 152.6 Hz, NCHP), 121.39 (d, JC,P = 3.7 Hz, CBr), 129.99 (2
C, d, JC,P = 4.9 Hz, CH), 131.19 (2 C, d, JC,P = 2.5 Hz, CH), 135.70
(d, JC,P = 7.3 Hz, Cquat), 172.99 (d, JC,P = 14.6 Hz, C=N).
31P NMR (CDCl3): d = 19.80.
MS: m/z = 417/415 (0.1/0.1, [M+]), 309 (50), 307 (52), 281 (87),
279 (100), 252 (41), 250 (41), 186 (83), 184 (95), 171 (81), 169
(76), 95 (85), 89 (36), 67 (28), 65 (20), 41 (25).
JH,P = 17.5 Hz, NCH2P), 4.16 [4 H, m, P(O)OCH2CH3], 7.69 (1 H,
d, JH,P = 3.6 Hz, HC=N).
13C NMR (CDCl3): d = 15.73 [2 P(O)OCH2CH3], 21.46 (2 CH2),
24.44 (CH2), 36.05 (2 CH2), 55.46 (d, JC,P = 153.8 Hz, NCH2P),
61.91 [2 C, d, JC,P = 7.3 Hz, P(O)OCH2CH3], 71.74 (CCl), 169.19
(d, JC,P = 15.8 Hz, C=N).
31P NMR (CDCl3): d = 22.01.
Diethyl [(2-Chloro-1-alkylidene)amino]methylphosphonates
10–13; General Procedure
In a 50 mL flask, the appropriate diethyl [(alkylidene)amino]meth-
ylphosphonate 6–9 (5 mmol) was dissolved in CCl4 (15 mL) and N-
MS: m/z = 260 (15), 242 (8), 207 (9), 193 (16), 152 (68), 150 (23),
125 (100), 122 (59), 108 (51), 95 (51), 86 (33), 51 (34), 49 (52).
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

PAPER
Synthesis and Aziridination of 1-Phosphono-2-aza-1,3-dienes
729
Diethyl {[(E)-2-Chloro-2-methyl-1-propylidene]amino}(phe-
Diethyl {[(E)-2-Chloro-2-methyl-1-propylidene]amino}(4-
nyl)methylphosphonate (11a)
methoxyphenyl)methylphosphonate (12a)
Synthesized according to the general procedure with imine 7a af-
fording 1.61 g of a crude reaction mixture containing 11a as a yel-
lowish oil.
Synthesized according to the general procedure with imine 8a af-
fording 1.75 g of crude reaction mixture containing 12a as a yellow-
ish oil.
IR (neat): 1712 cm–1.
IR (neat): 1710 cm–1.
1H NMR (CDCl3): d = 1.22 [3 H, t, J = 6.9 Hz, P(O)OCH2CH3],
1.23 [3 H, t, J = 6.9 Hz, P(O)OCH2CH3], 1.73 (3 H, s, CH3), 1.77 (3
H, s, CH3), 4.00 [4 H, m, P(O)OCH2CH3], 4.78 (1 H, d, JH,P = 18.8
Hz, NCHP), 7.32 (3 H, m, CH), 7.52 (2 H, m, CH), 7.84 (1 H, d,
1H NMR (CDCl3): d = 1.24 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.73 (3 H, s, CH3), 1.76 (3 H, s, CH3), 3.80 (3 H, s, OCH3), 4.01 [4
H, m, P(O)OCH2CH3], 4.72 (1 H, d, JH,P = 18.1 Hz, NCHP), 6.89 (2
H, d, J = 8.6 Hz, CH), 7.44 (2 H, dd, J = 8.9, 2.3 Hz, CH), 7.81 (1
H, d, JH,P = 4.6 Hz, HC=N).
JH,P = 4.9 Hz, HC=N).
13C NMR (CDCl3): d = 16.23 [d, JC,P = 3.7 Hz, P(O)OCH2CH3],
16.32 [d, JC,P = 3.7 Hz, P(O)OCH2CH3], 29.15 (CH3), 29.63 (CH3),
63.11 [d, JC,P = 7.3 Hz, P(O)OCH2CH3], 63.25 [d, JC,P = 7.3 Hz,
P(O)OCH2CH3], 67.92 (CCl), 72.28 (d, JC,P = 152.6 Hz, NCHP),
127.79 (d, JC,P = 3.7 Hz, CH), 128.31 (4 CH), 135.57 (d, JC,P = 8.5
Hz, Cquat), 168.18 (d, JC,P = 15.9 Hz, C=N).
13C NMR (CDCl3): d = 16.39 [2 C, JC,P = 4.9 Hz, P(O)OCH2CH3],
29.11 (CH3), 29.15 (CH3), 55.16 (OCH3), 62.92 [JC,P = 6.1 Hz,
P(O)OCH2CH3], 63.14 [JC,P = 7.3 Hz, P(O)OCH2CH3], 67.96
(CCl), 71.09 (JC,P = 153.8 Hz, NCHP), 113.76 (2 CH), 127.41 (d,
JC,P = 8.6 Hz, Cquat), 129.44 (2 C, d, JC,P = 6.1 Hz, CH), 159.23 (d,
JC,P = 3.7 Hz, COCH3), 167.94 (d, JC,P = 14.6 Hz, C=N).
31P NMR (CDCl3): d = 19.14.
MS: m/z = 333/331 (1/1, [M+]), 296 (24), 294 (25), 229 (42), 195
31P NMR (CDCl3): d = 19.91.
MS: m/z = 361 (1, [M+]), 258 (20), 257 (13), 228 (12), 226 (32), 224
(100), 188 (36), 155 (20), 135 (20), 134 (14), 121 (18), 91 (11), 77
(7), 40 (22).
(48), 159 (38), 136 (39), 109 (100), 107 (83), 79 (96), 53 (31).
Diethyl {[(E)-2-Chloro-2-ethyl-1-butylidene]amino}(phenyl)-
methylphosphonate (11b)
Synthesized according to the general procedure with imine 7b;
yield: 1.74 g (97%); yellowish oil.
Diethyl {[(E)-2-Chloro-2-ethyl-1-butylidene]amino}(4-meth-
oxyphenyl)methylphosphonate (12b)
Synthesized according to the general procedure with imine 8b;
yield: 1.93 g (99%); yellowish oil.
IR (neat): 1714 cm–1.
IR (neat): 1716 cm–1.
1H NMR (CDCl3): d = 0.96 (3 H, t, J = 7.3 Hz, CH3), 1.04 (3 H, t,
J = 7.3 Hz, CH3), 1.22 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.24 [3
H, t, J = 7.1 Hz, P(O)OCH2CH3], 2.04 (4 H, m, CH2), 4.01 [4 H, m,
P(O)OCH2CH3], 4.77 (1 H, d, JH,P = 18.5 Hz, NCHP), 7.33 (3 H, m,
CH), 7.51 (2 H, m, CH), 7.78 (1 H, d, JH,P = 4.9 Hz, HC=N).
13C NMR (CDCl3): d = 8.75 (2 CH3), 16.35 [2 C, d, JC,P = 4.9 Hz,
P(O)OCH2CH3], 31.61 (CH2), 32.20 (CH2), 63.05 [2 C, t, JC,P = 6.7
Hz, P(O)OCH2CH3], 72.28 (d, JC,P = 152.6 Hz, NCHP), 77.05
(CCl), 127.76 (d, JC,P = 2.4 Hz, CH), 128.27 (4 CH), 135.74 (d,
JC,P = 7.4 Hz, Cquat), 168.38 (d, JC,P = 15.8 Hz, C=N).
31P NMR (CDCl3): d = 19.83.
MS: m/z = 361/359 (2/1, [M+]), 353 (28), 330 (18), 325 (24), 323
(79), 321 (26), 228 (100), 222 (87), 200 (25), 186 (42), 172 (63),
125 (13), 91 (25).
1H NMR (CDCl3): d = 0.96 (3 H, t, J = 7.4 Hz, CH3), 1.04 (3 H, t,
J = 7.4 Hz, CH3), 1.24 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3], 2.03 (4
H, m, CH2), 3.80 (3 H, s, OCH3), 4.02 [4 H, m, P(O)OCH2CH3],
4.73 (1 H, d, JH,P = 17.8 Hz, NCHP), 6.89 (2 H, d, J = 8.6 Hz, CH),
7.44 (2 H, dd, J = 8.9, 2.3 Hz, CH), 7.76 (1 H, d, JH,P = 4.9 Hz,
HC=N).
13C NMR (CDCl3): d = 8.75 (2 CH3), 16.36 [d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 16.41 [d, JC,P = 4.8 Hz, P(O)OCH2CH3], 31.64
(CH2), 32.22 (CH2), 55.15 (OCH3), 62.94 [2 C, t, JC,P = 7.3 Hz,
P(O)OCH2CH3], 71.53 (JC,P = 153.8 Hz, NCHP), 76.84 (CCl),
113.78 (2 C, d, JC,P = 2.4 Hz, CH), 127.62 (d, JC,P = 7.3 Hz, Cquat),
129.37 (2 C, d, JC,P = 6.1 Hz, CH), 159.20 (d, JC,P = 3.7 Hz,
COCH3), 168.13 (d, JC,P = 15.8 Hz, C=N).
31P NMR (CDCl3): d = 20.14.
Diethyl {[(E)-(1-Chlorocyclohexyl)methylidene]amino}(phen-
yl)methylphosphonate (11c)
MS: m/z = 389 (2, [M+]), 359 (4), 257 (37), 256 (29), 253 (71), 251
(100), 216 (13), 136 (12), 134 (12), 121 (34), 91 (7).
Synthesized according to the general procedure with imine 7c;
yield: 1.77 g (95%); yellowish oil.
IR (neat): 1714 cm–1.
Diethyl {[(E)-(1-Chlorocyclohexyl)methylidene]amino}(4-meth-
oxyphenyl)methylphosphonate (12c)
Synthesized according to the general procedure with imine 8c;
yield: 1.95 g (97%); yellowish oil.
1H NMR (CDCl3): d = 1.23 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.24 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.58–1.80 (6 H, m, CH2),
2.00–2.08 (4 H, m, CH2), 4.01 [4 H, m, P(O)OCH2CH3], 4.77 (1 H,
d, JH,P = 18.5 Hz, NCHP), 7.33 (3 H, m, CH), 7.52 (2 H, m, CH),
7.79 (1 H, d, JH,P = 4.6 Hz, HC=N).
13C NMR (CDCl3): d = 16.36 [2 C, t, JC,P = 3.1 Hz, P(O)OCH2CH3],
22.14 (2 CH2), 25.14 (CH2), 36.76 (2 C, d, J = 6.1 Hz, CH2), 62.97
[d, JC,P = 6.1 Hz, P(O)OCH2CH3], 63.23 [d, JC,P = 7.3 Hz,
P(O)OCH2CH3], 73.15 (JC,P = 151.4 Hz, NCHP), 72.83 (CCl),
127.77 (d, JC,P = 3.6 Hz, CH), 128.29 (4 CH), 135.71 (d, JC,P = 8.5
Hz, Cquat), 168.29 (d, JC,P = 15.8 Hz, C=N).
31P NMR (CDCl3): d = 19.75.
MS: m/z = 373/371 (0.2/0.2, [M+]), 335 (11), 236 (30), 234 (88),
228 (100), 200 (25), 198 (40), 172 (23), 106 (39), 91 (59), 77 (16),
40 (61).
IR (neat): 1715 cm–1.
1H NMR (CDCl3): d = 1.24 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.59–1.80 (6 H, m, CH2), 1.99–2.07 (4 H, m, CH2), 3.80 (3 H, s,
OCH3), 4.02 [4 H, m, P(O)OCH2CH3], 4.72 (1 H, d, JH,P = 18.1 Hz,
NCHP), 6.89 (2 H, d, JH,P = 8.9 Hz, CH), 7.44 (2 H, dd, J = 8.9, 2.3
Hz, CH), 7.76 (1 H, d, JH,P = 4.9 Hz).
13C NMR (CDCl3): d = 16.36 [d, JC,P = 3.7 Hz, P(O)OCH2CH3],
16.45 [d, JC,P = 3.7 Hz, P(O)OCH2CH3], 22.17 (2 CH2), 25.14
(CH2), 36.73 (CH2), 36.80 (CH3), 55.16 (OCH3), 62.89 [d, JC,P = 7.3
Hz, P(O)OCH2CH3], 63.16 (d, JC,P = 7.3 Hz, P(O)OCH2CH3), 71.38
(d, JC,P = 152.6 Hz, NCHP), 72.81 (CCl), 113.78 (2 C, d, JC,P = 2.4
Hz, CH), 127.58 (d, JC,P = 7.4 Hz, Cquat), 129.42 (2 C, d, JC,P = 6.1
Hz, CH), 159.21 (d, JC,P = 2.5 Hz, COCH3), 168.05 (d, JC,P = 14.6
Hz, C=N).
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

730
B. Vanderhoydonck, C. V. Stevens
PAPER
31P NMR (CDCl3): d = 20.08.
MS: m/z = 403/401 (1/2, [M+]), 265 (13), 263 (100), 253 (37), 228
31P NMR (CDCl3): d = 18.90.
MS: m/z = 451/449 (3/4, [M+]), 416 (60), 415 (100), 414 (66), 413
(19), 155 (15), 135 (39), 121 (34), 93 (10).
(97), 314 (15), 184 (16), 171 (12), 169 (14), 93 (20).
Diethyl (4-Bromophenyl){[(E)-2-chloro-2-methyl-1-propyli-
dene]amino}methylphosphonate (13a)
Synthesized according to the general procedure with imine 9a af-
fording 1.97 g of crude reaction mixture containing 13a as a yellow-
ish oil.
1-Phosphono-2-aza-1,3-dienes 14–17; General Procedure
NaH (60% in mineral oil, 7.5 mmol) was weighed in a 50 mL flask
and was washed twice with pentane (15 mL). After decanting the
pentane and addition of THF (10 mL), a solution of the required di-
ethyl [(2-chloro-1-alkylidene)amino]methylphosphonate 10–13 (5
mmol) in THF (40 mL) was added dropwise. The flask was placed
under N2 and was stirred overnight at r.t. Then, the flask was fitted
with a reflux condenser and the mixture was heated under reflux.
The end of the reaction was monitored by TLC. The mixture was
cooled to r.t., poured into aq 0.1 M NaOH (25 mL) and extracted
with Et2O (3 × 20 mL). The combined organic layers were
(MgSO4) and filtered. Concentration of the reaction mixture under
reduced pressure gave phosphonoazadienes 14–17 as yellow oils in
moderate to good yields (51–83%) and satisfying purity (>90%).
IR (neat): 1714 cm–1.
1H NMR (CDCl3): d = 1.24 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.25 [3 H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.73 (3 H, s, CH3), 1.76 (3
H, s, CH3), 4.03 [4 H, m, P(O)OCH2CH3], 4.72 (1 H, d, JH,P = 18.8
Hz, NCHP), 7.47 (4 H, m, CH), 7.84 (1 H, d, JH,P = 4.6 Hz, HC=N).
13C NMR (CDCl3): d = 16.32 [2 C, t, JC,P = 4.9 Hz, P(O)OCH2CH3],
29.09 (CH3), 29.63 (CH3), 63.16 [d, JC,P = 7.3 Hz, P(O)OCH2CH3],
63.38 [d, JC,P = 7.3 Hz, P(O)OCH2CH3], 67.76 (CCl), 71.07 (d,
J
C,P = 151.4 Hz, NCHP), 121.77 (d, JC,P = 3.6 Hz, CBr), 129.94 (2
Diethyl (E)-{[(Z)-2-Methylprop-1-enyl]imino}methylphospho-
nate (14a)
Synthesized according to the general procedure with imine 10a;
yield: 0.91 g (83%); yellow oil.
C, d, JC,P = 6.1 Hz, CH), 131.41 (2 C, d, JC,P = 2.4 Hz, CH), 134.76
(d, JC,P = 8.5 Hz, Cquat), 168.62 (d, JC,P = 14.6 Hz, C=N).
31P NMR (CDCl3): d = 18.76.
MS: m/z = 376/374 (1/1, [M+ – Cl]), 308 (51), 306 (50), 274 (100),
272 (77), 206 (27), 204 (20), 186 (27), 184 (30), 112 (16), 110 (16),
91 (29).
IR (neat): 1648, 1561 cm–1.
1H NMR (CDCl3): d = 1.37 [6 H, t, J = 7.3 Hz, P(O)OCH2CH3],
1.86 (3 H, s, CH3), 2.05 (3 H, s, CH3), 4.22 [4 H, m,
P(O)OCH2CH3], 6.57 (1 H, d, J = 1.3 Hz, CH), 7.70 (1 H, d,
JH,P = 62.7 Hz, HCP).
Diethyl (4-Bromophenyl){[(E)-2-chloro-2-ethyl-1-butyl-
idene]amino}methylphosphonate (13b)
13C NMR (CDCl3): d = 16.40 [2 C, d, JCP = 6.1 Hz, P(O)OCH2CH3],
18.42 (CH3), 22.93 (CH3), 62.93 [2 C, d, JCP = 6.1 Hz,
P(O)OCH2CH3], 138.57 (d, JC,P = 40.3 Hz, CH), 143.86 (Cquat),
151.45 (d, JC,P = 228.2 Hz, CHP).
31P NMR (CDCl3): d = 8.85.
MS: m/z = 219 (18, [M+]), 138 (19), 111 (43), 110 (22), 83 (34), 82
Synthesized according to the general procedure with imine 9b;
yield: 2.15 g (98%); yellowish oil.
IR (neat): 1716 cm–1.
1H NMR (CDCl3): d = 0.96 (3 H, t, J = 7.3 Hz, CH3), 1.04 (3 H, t,
J = 7.4 Hz, CH3), 1.24 [3 H, t, J = 6.9 Hz, P(O)OCH2CH3], 1.25 [3
H, t, J = 6.9 Hz, P(O)OCH2CH3], 2.03 (4 H, q, J = 7.5 Hz, CH2),
4.02 [4 H, m, P(O)OCH2CH3], 4.70 (1 H, d, JH,P = 18.5 Hz, NCHP),
7.44 (4 H, m, CH), 7.78 (1 H, d, JH,P = 4.9 Hz, HC=N).
(100), 81 (53), 80 (20), 65 (18), 55 (55), 39 (22).
13C NMR (CDCl3): d = 8.59 (2 CH3), 16.24 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 31.45 (CH2), 32.02 (CH2), 63.04 [2 C, t, JC,P = 6.1
Hz, P(O)OCH2CH3], 71.46 (d, JC,P = 151.4 Hz, NCHP), 76.73
(CCl), 121.63 (d, JC,P = 4.8 Hz, CBr), 129.74 (2 C, d, JC,P = 4.9 Hz,
CH), 131.30 (2 C, d, JC,P = 2.5 Hz, CH), 134.81 (d, JC,P = 7.3 Hz,
Diethyl (E)-{[(Z)-2-Ethylbut-1-enyl]imino}methylphosphonate
(14b)
Synthesized according to the general procedure with imine 10b;
yield: 0.93 g (75%); yellow oil.
IR (neat): 1635, 1560 cm–1.
Cquat), 168.67 (d, JC,P = 15.8 Hz, C=N).
1H NMR (CDCl3): d = 1.04 (3 H, t, J = 7.6 Hz, CH3), 1.08 (3 H, t,
J = 7.6 Hz, CH3), 1.36 [6 H, t, J = 6.8 Hz, P(O)OCH2CH3], 2.20 (2
H, q, J = 7.6 Hz, CH2), 2.57 (2 H, q, J = 7.6 Hz, CH2), 4.22 [4 H, m,
P(O)OCH2CH3], 6.53 (1 H, s, CH), 7.72 (1 H, d, JH,P = 62.7 Hz,
CHP).
31P NMR (CDCl3): d = 18.99.
MS: m/z = 404/402 (5/4, [M+ – Cl]), 403 (19), 401 (18), 308 (94),
306 (93), 302 (100), 300 (79), 171 (41), 169 (40), 89 (17).
13C NMR (CDCl3): d = 12.38 (CH3), 13.14 (CH3), 16.40 [2 C, d,
Diethyl (4-Bromophenyl){[(E)-(1-chlorocyclohexyl)methyli-
dene]amino}methylphosphonate (13c)
Synthesized according to the general procedure with imine 9c;
yield: 2.14 g (95%); yellowish oil.
J
C,P = 6.1 Hz, P(O)OCH2CH3], 23.38 (CH2), 27.08 (CH2), 62.94 [2
C, d, JC,P = 6.1 Hz, P(O)OCH2CH3], 137.10 (d, JC,P = 40.3 Hz, CH),
151.83 (d, JC,P = 228.3 Hz, CHP), 154.59 (Cquat).
31P NMR (CDCl3): d = 8.86.
IR (neat): 1709 cm–1.
1H NMR (CDCl3): d = 1.24 [3 H, t, J = 6.9 Hz, P(O)OCH2CH3],
1.25 [3 H, t, J = 6.9 Hz, P(O)OCH2CH3], 1.59–1.80 (6 H, m, CH2),
1.99–2.06 (4 H, m, CH2), 4.03 [4 H, m, P(O)OCH2CH3], 4.71 (1 H,
d, JH,P = 18.8 Hz, NCHP), 7.46 (4 H, m, CH), 7.78 (1 H, d, JH,P = 4.9
Hz, HC=N).
MS: m/z = 247 (16, [M+]), 138 (14), 111 (42), 110 (100), 109 (43),
94 (33), 82 (28), 65 (17), 55 (36), 41 (22).
Diethyl (E)-{[(Z)-Cyclohexylidenemethyl]imino}methylphos-
phonate (14c)
Synthesized according to the general procedure with imine 10c;
yield: 1.04 g (80%); yellow oil.
IR (neat): 1638, 1556 cm–1.
1H NMR (CDCl3): d = 1.36 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.61 (6 H, m, CH2), 2.21 (2 H, m, CH2), 2.74 (2 H, m, CH2), 4.22 [4
13C NMR (CDCl3):
d = 16.38 [2 C, d, JC,P = 3.7 Hz,
P(O)OCH2CH3], 22.14 (2 CH2), 25.08 (CH2), 36.67 (CH2), 36.76
(CH2), 63.04 [d, JC,P = 7.3 Hz, P(O)OCH2CH3], 63.30 [d, JC,P = 8.5
Hz, P(O)OCH2CH3], 71.40 (d, JC,P = 152.6 Hz, NCHP), 72.59
(CCl), 121.72 (d, JC,P = 4.9 Hz, CBr), 129.91 (2 C, d, JC,P = 6.1 Hz,
CH), 131.39 (2 C, d, JC,P = 2.4 Hz, CH), 134.90 (d, JC,P = 8.5 Hz,
Cquat), 168.64 (d, JC,P = 14.6 Hz, C=N).
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

PAPER
Synthesis and Aziridination of 1-Phosphono-2-aza-1,3-dienes
731
H, m, P(O)OCH2CH3], 6.54 (1 H, d, JH,P = 1.0 Hz, CH), 7.72 (1 H,
d, JH,P = 63.0 Hz, CHP).
13C NMR (CDCl3):
d =
16.34 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 26.68 (CH2), 27.60 (CH2), 28.43 (CH2), 28.71
(CH2), 34.48 (CH2), 63.21 [2 C, d, JC,P = 6.1 Hz, P(O)OCH2CH3],
128.04 (d, JC,P = 13.4 Hz, CH), 128.30 (2 C, d, JC,P = 4.9 Hz, CH),
128.42 (2 CH), 128.90 (d, JC,P = 34.1 Hz, NCH), 134.28 (JC,P = 31.8
Hz, Cquat), 151.17 (Cquat), 159.50 (JC,P = 224.8 Hz, CP).
13C NMR (CDCl3):
d = 16.43 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 26.63 (CH2), 27.62 (CH2), 28.41 (CH2), 28.91
(CH2), 34.68 (CH2), 62.97 [2 C, d, JC,P = 7.3 Hz, P(O)OCH2CH3],
135.80 (d, JC,P = 40.3 Hz, CH), 151.10 (d, JC,P = 2.4 Hz, Cquat),
151.97 (d, JC,P = 227.0 Hz, CHP).
31P NMR (CDCl3): d = 8.93.
31P NMR (CDCl3): d = 8.27.
MS: m/z = 259 (14, [M+]), 152 (37), 125 (46), 122 (100), 121 (61),
MS: m/z = 337 (66, [M+ + 2]), 200 (42), 199 (100), 198 (51), 170
(34), 135 (52), 105 (30), 96 (37), 95 (33), 77 (23), 67 (22), 55 (18).
111 (25), 95 (33), 93 (38), 83 (19), 67 (20), 41 (27).
Diethyl (E)-(4-Methoxyphenyl){[(Z)-2-methylprop-1-enyl]imi-
no}methylphosphonate (16a)
Synthesized according to the general procedure with imine 12a;
yield: 0.83 g (51%); yellow oil.
Diethyl (E)-{[(Z)-2-Methylprop-1-enyl]imino}(phenyl)methyl-
phosphonate (15a)
Synthesized according to the general procedure with imine 11a;
yield: 1.15 g (78%); yellow oil.
IR (neat): 1606, 1508 cm–1.
IR (neat): 1635, 1444 cm–1.
1H NMR (CDCl3): d = 1.30 [6 H, t, J = 6.9 Hz, P(O)OCH2CH3],
1.78 (3 H, s, CH3), 2.08 (3 H, s, CH3), 3.83 (3 H, s, OCH3), 4.20 [4
H, dquint, J = 7.2 Hz, JH,P = 1.8 Hz, P(O)OCH2CH3], 6.75 (1 H, d,
1H NMR (CDCl3): d = 1.29 [6 H, t, J = 7.3 Hz, P(O)OCH2CH3],
1.77 (3 H, s, CH3), 2.09 (3 H, s, CH3), 4.22 [4 H, dquint, J = 7.3 Hz,
JH,P = 2.1 Hz, P(O)OCH2CH3], 6.68 (1 H, s, NCH), 7.37 (5 H, m,
CH).
JH,P = 1.3 Hz, NCH), 6.93 (2 H, d, J = 8.6 Hz, CH), 7.34 (2 H, d,
J = 8.6 Hz, CH).
13C NMR (CDCl3):
d = 16.25 [2 C, d, JC,P = 6.1 Hz,
13C NMR (CDCl3):
d = 16.32 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 18.15 (CH3), 23.22 (CH3), 55.15 (OCH3), 63.06 [2
C, JC,P = 6.1 Hz, P(O)OCH2CH3], 113.67 (2 CH), 126.23 (d,
JC,P = 33.0 Hz, Cquat), 129.92 (2 C, d, JC,P = 4.9 Hz, CH), 131.91 (d,
P(O)OCH2CH3], 18.26 (CH3), 23.29 (d, JC,P = 2.5 Hz, CH3), 63.19
[2 C, d, JC,P = 6.1 Hz, P(O)OCH2CH3], 128.33 (2 C, d, JC,P = 3.7 Hz,
CH), 128.42 (2 CH), 129.11 (CH), 131.91 (d, JC,P = 31.8 Hz, NCH),
134.21 (d, JC P = 31.7 Hz, Cquat), 143.50 (d, JC,P = 2.5 Hz, Cquat),
159.52 (d, JC,P = 225.8 Hz, CP).
JC,P = 31.7 Hz, NCH), 142.64 (Cquat), 158.96 (d, JC,P = 227.0 Hz,
CP), 160.02 (COCH3).
31P NMR (CDCl3): d = 9.09.
MS: m/z = 327 (82, [M+ + 2]), 255 (11), 190 (59), 189 (100), 173
(20), 136 (33), 135 (63), 120 (13), 92 (11), 86 (31), 84 (42), 77 (15),
49 (19).
31P NMR (CDCl3): d = 8.80.
MS: m/z = 297 (54, [M+ + 2]), 244 (22), 229 (37), 195 (56), 160 (68),
159 (100), 158 (65), 144 (28), 135 (64), 105 (54), 92 (37), 81 (36),
77 (35).
Diethyl (E)-{[(Z)-2-Ethylbut-1-enyl]imino}(4-methoxyphen-
yl)methylphosphonate (16b)
Synthesized according to the general procedure with imine 12b;
yield: 1.15 g (65%); yellow oil.
Diethyl (E)-{[(Z)-2-Ethylbut-1-enyl]imino}(phenyl)methyl-
phosphonate (15b)
Synthesized according to the general procedure with imine 11b;
yield: 1.20 g (74%); yellow oil.
IR (neat): 1605, 1508 cm–1.
IR (neat): 1626, 1443 cm–1.
1H NMR (CDCl3): d = 0.98 (3 H, t, J = 7.4 Hz, CH3), 1.07 (3 H, t,
J = 7.6 Hz, CH3), 1.30 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3], 2.12 (2
H, q, J = 7.5 Hz, CH2), 2.60 (2 H, q, J = 7.5 Hz, CH2), 4.20 [4 H,
dquint, J = 7.1 Hz, JH,P = 1.6 Hz, P(O)OCH2CH3], 6.73 (1 H, s,
NCH), 6.93 (2 H, d, J = 8.2 Hz, CH), 7.36 (2 H, dd, J = 8.9 Hz,
JH,P = 1.0 Hz, CH).
13C NMR (CDCl3): d = 11.97 (CH3), 12.62 (CH3), 15.72 [2 C, d,
JC,P = 6.1 Hz, P(O)OCH2CH3], 22.45 (CH2), 26.87 (CH2), 54.56
(OCH3), 62.51 [2 C, d, JC,P = 6.1 Hz, P(O)OCH2CH3], 113.14
(2 CH), 125.62 (d, JC,P = 34.2 Hz, Cquat), 129.46 (2 C, d, JC,P = 3.6
Hz, CH), 130.00 (d, JC,P = 32.9 Hz, NCH), 152.34 (Cquat), 158.91 (d,
JC,P = 225.9 Hz, CP), 159.64 (COCH3).
1H NMR (CDCl3): d = 0.97 (3 H, t, J = 7.6 Hz, CH3), 1.07 (3 H, t,
J = 7.6 Hz, CH3), 1.29 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3], 2.11 (2
H, q, J = 7.5 Hz, CH2), 2.62 (2 H, q, J = 7.5 Hz, CH2), 4.22 [4 H,
dquint, J = 7.2 Hz, JH,P = 2.0 Hz, P(O)OCH2CH3], 6.66 (1 H, s,
NCH), 7.39 (5 H, m, CH).
13C NMR (CDCl3): d = 11.77 (CH3), 12.47 (CH3), 15.55 [2 C, d,
JC,P = 6.1 Hz, P(O)OCH2CH3], 22.28 (CH2), 26.74 (CH2), 62.41 [2
C, d, JC,P = 7.3 Hz, P(O)OCH2CH3], 127.52 (2 C, d, JC,P = 3.7 Hz,
CH), 127.65 (2 CH), 128.43 (CH), 129.75 (d, JC,P = 32.9 Hz, NCH),
133.44 (d, JC,P = 31.8 Hz, Cquat), 153.10 (Cquat), 159.28 (d,
JC,P = 227.1 Hz, CP).
31P NMR (CDCl3): d = 8.37.
MS: m/z = 323 (36, [M+]), 322 (16), 187 (22), 186 (100), 170 (20),
31P NMR (CDCl3): d = 8.79.
MS: m/z = 354 (2, [M+ + 1]), 353 (12) [M+], 217 (19), 216 (100),
124 (14), 105 (11), 104 (32), 83 (11), 77 (10), 55 (27), 41 (18).
200 (10), 172 (7), 163 (7), 135 (13), 134 (30), 121 (24), 99 (32).
Diethyl (E)-{[(Z)-Cyclohexylidenemethyl]imino}(phenyl)meth-
ylphosphonate (15c)
Synthesized according to the general procedure with imine 11c;
yield: 1.21 g (72%); yellow oil.
Diethyl (E)-{[(Z)-Cyclohexylidenemethyl]imino}(4-methoxy-
phenyl)methylphosphonate (16c)
Synthesized according to the general procedure with imine 12c;
yield: 1.13 g (62%); yellow oil.
IR (neat): 1628, 1444 cm–1.
IR (neat): 1606, 1509 cm–1.
1H NMR (CDCl3): d = 1.28 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.59 (6 H, m, CH2), 2.10 (2 H, m, CH2), 2.73 (2 H, m, CH2), 4.17 [4
H, dquint, J = 7.2 Hz, JH,P = 2.6 Hz, P(O)OCH2CH3], 6.66 (1 H, br
s, NCH), 7.37 (5 H, m, CH).
1H NMR (CDCl3): d = 1.29 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.59 (6 H, br s, CH2), 2.11 (2 H, m, CH2), 2.70 (2 H, m, CH2), 3.84
(3 H, s, OCH3), 4.17 [4 H, dquint, J = 7.2 Hz, JH,P = 2.2 Hz,
P(O)OCH2CH3], 6.73 (1 H, s, NCH), 6.93 (2 H, d, J = 8.2 Hz, CH),
7.34 (2 H, d, J = 8.2 Hz, CH).
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

732
B. Vanderhoydonck, C. V. Stevens
16.36 [2 C, d, JC,P = 6.1 Hz,
PAPER
13C NMR (CDCl3):
d
=
s, NCH), 7.24 (2 H, d, J = 8.1 Hz, CH), 7.56 (2 H, d, J = 7.9 Hz,
P(O)OCH2CH3], 26.72 (CH2), 27.62 (CH2), 28.46 (CH2), 28.71
(CH2), 34.50 (CH2), 55.22 (OCH3), 63.12 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 113.80 (2 CH), 126.33 (d, JC,P = 32.9 Hz, Cquat),
129.11 (d, JC,P = 31.6 Hz, NCH), 130.03 (2 C, d, JC,P = 3.6 Hz, CH),
150.19 (JC,P = 2.5 Hz, COCH3), 159.46 (JC,P = 227 Hz, CP), 160.19
(Cquat).
CH),
13C NMR (CDCl3):
d = 16.36 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 26.61 (CH2), 27.58 (CH2), 28.39 (CH2), 28.73
(CH2), 34.52 (CH2), 63.27 [2 C, d, JC,P = 7.4 Hz, P(O)OCH2CH3],
123.48 (CBr), 128.75 (d, JC,P = 31.7 Hz, NCH), 130.02 (2 C,
J
C,P = 3.6 Hz, CH), 131.70 (2 CH), 132.99 (d, JC,P = 31.7 Hz, Cquat),
152.09 (d, JC,P = 2.5 Hz, Cquat), 158.34 (JC,P = 229.5 Hz, CP).
31P NMR (CDCl3): d = 9.20.
MS: m/z = 367 (24, [M+ + 2]), 366 (97), 365 (2), 230 (69), 229 (100),
187 (30), 165 (29), 136 (30), 135 (24), 122 (29), 96 (20), 83 (16), 55
(21).
31P NMR (CDCl3): d = 8.43.
MS: m/z = 415/413 (15/16, [M+]), 414 (69), 412 (68), 281 (98), 279
(100), 241 (59), 239 (63), 188 (46), 186 (53), 142 (17), 140 (18), 89
(86), 87 (98).
Diethyl (E)-(4-Bromophenyl){[(Z)-2-methylprop-1-enyl]imi-
no}methylphosphonate (17a)
Synthesized according to the general procedure with imine 13a;
yield: 1.37 g (73%); yellow oil.
2-(Diethylphosphono)-1-vinylaziridines 18a–c; General Proce-
dure
To a solution of 1-phosphono-2-aza-1,3-dienes 14a–c (5 mmol) in
Et2O (5 mL) were added approximately 5 equivalents of diaz-
omethane (25 mmol) (prepared from N-methyl-N-nitroso-p-tolue-
nesulfonamide) in Et2O at 0 °C. The mixture was stirred for 5 h at
r.t. and the solvent was evaporated under reduced pressure to give
2-(diethylphosphono)-1-vinylaziridines 18a–c in good yields (68–
93%). Supplementary purification could be done by flash chroma-
tography leading to aziridine 18 as a yellowish oil with a purity of
>95%.
IR (neat): 1635, 1586 cm–1.
1H NMR (CDCl3): d = 1.31 [6 H, t, J = 6.9 Hz, P(O)OCH2CH3],
1.78 (3 H, s, CH3), 2.09 (3 H, s, CH3), 4.21 [4 H, dquint, J = 7.3 Hz,
JH,P = 1.9 Hz, P(O)OCH2CH3], 6.64 (1 H, d, JH,P = 1.3 Hz, NCH),
7.23 (2 H, dd, J = 8.4 Hz, JH,P = 0.8 Hz, CH), 7.54 (2 H, d, J = 8.2
Hz, CH).
13C NMR (CDCl3): d = 16.35 [2 C, d, JCP = 4.9 Hz, P(O)OCH2CH3],
18.29 (CH3), 23.32 (CH3), 63.23 [2 C, JC,P = 7.3 Hz,
P(O)OCH2CH3], 123.50 (CBr), 130.00 (2 C, d, JC,P = 3.7 Hz, CH),
131.68 (2 CH), 131.69 (d, JC,P = 31.7 Hz, NCH), 132.98 (d,
2-(Diethylphosphono)-1-(2-methylprop-1-enyl)aziridine (18a)
Synthesized according to the general procedure with phospho-
noazadiene 14a; yield: 1.09 g (93%); yellow oil. After flash chro-
matography, 0.67g (57%) of 18a was obtained as a yellowish oil;
Rf 0.36 [CHCl3–MeCN, 80:20 (1% Et3N)].
JC,P = 33.0 Hz, Cquat), 144.36 (d, JC,P = 2.4 Hz, Cquat), 158.10 (d,
JC,P = 228.3 Hz, CP).
31P NMR (CDCl3): d = 8.31.
MS: m/z = 375/373 (10/12, [M+]), 374 (52), 372 (53), 352 (65), 239
(98), 237 (100), 185 (34), 183 (32), 122 (22), 120 (27), 50 (51), 48
(52).
IR (neat): 1675 cm–1.
1H NMR (CDCl3): d = 1.34 [6 H, t, J = 6.9 Hz, P(O)OCH2CH3],
1.58 (3 H, s, CH3), 1.80 (3 H, s, CH3), 1.71–1.88 (2 H, m, NCH2,
NCHP), 2.31–2.37 (1 H, m, NCH2), 4.17 [4 H, m, P(O)OCH2CH3],
5.20 (1 H, s, CH).
Diethyl (E)-(4-Bromophenyl){[(Z)-2-ethylbut-1-enyl]imino}me-
thylphosphonate (17b)
Synthesized according to the general procedure with imine 13b;
yield: 1.41 g (70%); yellow oil.
13C NMR (CDCl3):
d = 16.44 [2 C, d, JC,P = 3.1 Hz,
P(O)OCH2CH3], 17.02 (CH3), 21.98 (CH3), 33.29 (d, JC,P = 213.7
Hz, NCHP), 33.30 (d, JC,P = 4.9 Hz, NCH2), 62.53 [2 C, d,
IR (neat): 1708, 1586 cm–1.
JC,P = 11.0 Hz, P(O)OCH2CH3], 125.78 (Cquat), 135.69 (d, JC,P = 6.1
1H NMR (CDCl3): d = 0.98 (3 H, t, J = 7.4 Hz, CH3), 1.06 (3 H, t,
J = 7.6 Hz, CH3), 1.31 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3], 2.12 (2
H, q, J = 7.5 Hz, CH2), 2.60 (2 H, q, J = 7.6 Hz, CH2), 4.20 [4 H,
dquint, J = 7.2 Hz, JH,P = 1.7 Hz, P(O)OCH2CH3], 6.62 (1 H, s,
NCH), 7.25 (2 H, d, J = 8.6 Hz, CH), 7.56 (2 H, d, J = 8.2 Hz, CH).
Hz, CH).
31P NMR (CDCl3): d = 22.52.
MS: m/z = 233 (11, [M+]), 165 (61), 137 (44), 125 (19), 109 (100),
96 (86), 94 (45), 91 (30), 82 (28), 65 (18), 55 (23), 41 (34).
Anal. Calcd for C10H20NO3P: C, 51.49; H, 8.64; N, 6.01. Found: C,
51.56; H, 8.65; N, 5.97.
13C NMR (CDCl3): d = 11.95 (CH3), 12.63 (CH3), 15.75 [2 C, d,
J
C,P = 6.1 Hz, P(O)OCH2CH3], 22.52 (CH2), 26.97 (CH2), 62.69 [2
C, d, JC,P = 6.1 Hz, P(O)OCH2CH3], 122.95 (CBr), 129.46 (2 C, d,
C,P = 3.6 Hz, CH), 130.16 (d, JC,P = 40.3 Hz, NCH), 131.07 (2 CH),
132.33 (d, JC,P = 31.8 Hz, Cquat), 154.30 (d, JC,P = 2.5 Hz, Cquat),
157.83 (d, JC,P = 228.2 Hz, CP).
31P NMR (CDCl3): d = 7.97.
MS: m/z = 403/401 (2/3, [M+]), 402 (12), 400 (12), 265 (96), 263
2-(Diethylphosphono)-1-(2-ethylbut-1-enyl)aziridine (18b)
Synthesized according to the general procedure with phospho-
noazadiene 14b; yield: 0.89 g (68%). After flash chromatography,
0.39g (30%) of 18b was obtained as a yellowish oil; Rf 0.33
[CHCl3–MeCN, 80:20 (1% Et3N].
J
IR (neat): 1657 cm–1.
(100), 184 (32), 182 (26), 157 (10), 154 (11), 55 (32), 41 (17).
1H NMR (CDCl3): d = 0.95 (3 H, t, J = 7.6 Hz, CH3), 1.01 (3 H, t,
J = 7.6 Hz, CH3), 1.34 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3], 1.75–
1.85 (2 H, m, NCH2, NCHP), 1.93 (2 H, q, J = 7.4 Hz, CH2), 2.32
(2 H, q, J = 7.4 Hz, CH2), 2.27–2.37 (1 H, m, NCH2), 4.17 [4 H, m,
P(O)OCH2CH3], 5.13 (1 H, s, CH).
13C NMR (CDCl3): d = 12.54 (CH3), 12.74 (CH3), 16.47 [2 C, d,
JC,P = 6.1 Hz, P(O)OCH2CH3], 21.83 (CH2), 25.93 (CH2), 33.52 (d,
Diethyl (E)-(4-Bromophenyl){[(Z)-cyclohexylidenemethyl]imi-
no}methylphosphonate (17c)
Synthesized according to the general procedure with imine 13c;
yield: 1.66 g (80%); yellow oil.
IR (neat): 1630, 1585 cm–1.
1H NMR (CDCl3): d = 1.30 [6 H, t, J = 7.1 Hz, P(O)OCH2CH3],
1.60 (6 H, br s, CH2), 2.11 (2 H, m, CH2), 2.70 (2 H, m, CH2), 4.20
[4 H, dquint, J = 7.3 Hz, JH,P = 2.1 Hz, P(O)OCH2CH3], 6.62 (1 H,
JC,P = 213.6 Hz, NCHP), 33.42 (d, JC,P = 4.8 Hz, NCH2), 62.57 [2 C,
d, JC,P = 6.1 Hz, P(O)OCH2CH3], 134.77 (d, JC,P = 7.3 Hz, CH),
137.55 (Cquat).
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

PAPER
Synthesis and Aziridination of 1-Phosphono-2-aza-1,3-dienes
733
31P NMR (CDCl3): d = 22.50.
MS: m/z = 261 (6, [M+]), 246 (12), 165 (78), 137 (59), 125 (42), 124
cis-3-Diethylphosphono-2-ethoxycarbonyl-1-(2-ethylbut-1-
enyl)aziridine (19b)
Synthesized according to the general procedure with phospho-
noazadiene 14b ; yield: 0.75 g (45%); yellowish oil; Rf 0.27
[EtOAc–petroleum ether, 1:1 (1% Et3N)].
IR (neat): 1754 cm–1.
(43), 109 (100), 108 (41), 91 (25), 82 (21), 65 (14), 55 (21), 41 (22).
Anal. Calcd for C12H24NO3P: C, 55.16; H, 9.26; N, 5.36. Found: C,
55.23; H, 9.21; N, 5.33.
2-Diethylphosphono-1-(cyclohexylidenemethyl)aziridine (18c)
Synthesized according to the general procedure with phospho-
noazadiene 14c; yield: 0.99 g (72%). After flash chromatography,
0.40 g (29%) of 18c was obtained as a yellowish oil; Rf 0.52
[CHCl3–MeCN, 80:20 (1% Et3N)].
1H NMR (CDCl3): d = 0.94 (3 H, t, J = 7.4 Hz, CH3), 1.01 (3 H, t,
J = 7.6 Hz, CH3), 1.30 [6 H, m, P(O)OCH2CH3], 1.93 (2 H, q,
J = 7.3 Hz, CH2), 2.16 (1 H, dd, JH,P = 18.8 Hz, J = 6.9 Hz, NCHP),
2.32 (2 H, q, J = 7.6 Hz, CH2), 2.66 (1 H, dd, JH,P = 5.8 Hz, J = 7.0
Hz, NCH), 4.19 [4 H, m, P(O)OCH2CH3], 5.21 (1 H, s, CH).
IR (neat): 1673 cm–1.
13C NMR (CDCl3): d = 12.31 (2 CH3), 13.82 (CH3), 16.13 [2 C, d,
JC,P = 6.1 Hz, P(O)OCH2CH3], 21.65 (CH2), 25.64 (CH2), 39.67 (d,
1H NMR (CDCl3): d = 1.34 [6 H, t, J = 6.9 Hz, P(O)OCH2CH3],
1.52 (6 H, m, CH2), 1.74–1.85 (2 H, m, NCH2, NCHP), 1.94 (2 H,
m, CH2), 2.38 (2 H, m, CH2), 2.32–2.37 (1 H, m, NCH2), 4.16 [4 H,
m, P(O)OCH2CH3], 5.19 (1 H, s, CH).
13C NMR (CDCl3):
P(O)OCH2CH3], 26.68 (CH2), 27.24 (CH2), 27.60 (CH2), 28.30
(CH2), 33.38 (d, JC,P = 213.7 Hz, NCHP), 33.12 (CH2), 33.50 (d,
JC,P = 216.1 Hz, NCHP), 43.83 (d, JC,P = 4.9 Hz, NCH), 61.08
(OCH2), 62.38 [d, JC,P = 6.1 Hz, P(O)OCH2CH3], 62.74 [d,
JC,P = 6.1 Hz, P(O)OCH2CH3], 132.74 (d, JC,P = 7.4 Hz, CH),
138.29 (Cquat), 166.77 (d, JC,P = 2.4 Hz, C=O).
31P NMR (CDCl3): d = 18.53.
d = 16.48 [2 C, d, JC,P = 6.1 Hz,
MS: m/z = 333 (4, [M+]), 259 (100), 236 (17), 196 (51), 135 (27),
JC,P = 6.2 Hz, NCH2), 62.55 [2 C, d, JC,P = 19.0 Hz,
122 (31), 108 (16), 81 (15).
P(O)OCH2CH3], 133.07 (d, JC,P = 7.3 Hz, CH), 133.51 (Cquat).
31P NMR (CDCl3): d = 22.61.
Anal. Calcd for C15H28NO5P: C, 54.04; H, 8.47; N, 4.20. Found: C,
54.12; H, 8.50; N, 4.18.
MS: m/z = 273 (10, [M+]), 165 (61), 137 (79), 136 (75), 125 (23),
122 (44), 109 (100), 108 (30), 91 (33), 83 (36), 67 (21), 54 (25), 53
(19), 41 (23).
cis-1-Cyclohexylidenemethyl-3-diethylphosphono-2-(ethoxy-
carbonyl)aziridine (19c)
Synthesized according to the general procedure with phospho-
noazadiene 14c; yield: 0.74 g (43%); yellowish oil; Rf 0.31
[EtOAc–petroleum ether, 1:1 (1% Et3N)].
Anal. Calcd for C13H24NO3P: C, 57.13; H, 8.85; N, 5.12. Found: C,
57.05; H, 8.84; N, 5.16.
IR (neat): 1753 cm–1.
3-Diethylphosphono-2-ethoxycarbonyl-1-vinylaziridines 19;
General Procedure
1H NMR (CDCl3): d = 1.31 [3 H, t, J = 6.9 Hz, P(O)OCH2CH3],
1.33 [3 H, t, J = 6.9 Hz, P(O)OCH2CH3], 1.53 (6 H, m, CH2), 1.95
(2 H, m, CH2), 2.16 (1 H, dd, JH,P = 18.8 Hz, J = 6.9 Hz, NCHP),
2.40 (2 H, m, CH2), 2.69 (1 H, dd, JH,P = 5.8 Hz, J = 6.9 Hz, NCH),
4.21 [4 H, m, P(O)OCH2CH3], 5.31 (1 H, s, CH).
13C NMR (CDCl3): d = 13.95 (CH3), 16.27 [2 C, JC,P = 6.1 Hz,
P(O)OCH2CH3], 26.40 (CH2), 26.99 (CH2), 27.31 (CH2), 28.07
(CH2), 32.90 (CH2), 39.79 (d, JC,P = 216.1 Hz, NCHP), 44.01 (d,
To a solution of 1-phosphono-2-aza-1,3-diene 14 (5 mmol) in
CH2Cl2 (25 mL) was added Yb(OTf)3 (0.5 mmol). The mixture was
placed under N2 and stirred for 5 min at r.t. Ethyl diazoacetate (310
mg, 5.5 mmol) was added dropwise using a syringe. The reaction
mixture was stirred for 24 h at r.t. after which the solvent was evap-
orated under reduced pressure. The crude reaction mixture was pu-
rified by means of flash chromatography to afford the pure cis-
aziridines 19 as yellowish oils.
JC,P = 4.9 Hz, NCH), 61.31 (OCH3), 62.60 [d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 62.83 [d, JC,P = 6.1 Hz, P(O)OCH2CH3], 131.04
(d, JC,P = 6.1 Hz, CH), 134.16 (Cquat), 166.93 (C=O).
31P NMR (CDCl3): d = 18.61.
MS: m/z = 345 (5, [M+]), 300 (2), 272 (100), 208 (63), 162 (41), 135
(49), 134 (51), 122 (27), 93 (21), 81 (26).
cis-3-Diethylphosphono-2-ethoxycarbonyl-1-(2-methylprop-1-
enyl)aziridine (19a)
Synthesized according to the general procedure with phospho-
noazadiene 14a; yield: 0.61 g (40%); yellowish oil; Rf 0.20
[EtOAc–petroleum ether, 1:1 (1% Et3N)].
IR (neat): 1753 cm–1.
Anal. Calcd for C16H28NO5P: C, 55.64; H, 8.17; N, 4.06. Found: C,
55.70; H, 8.16; N, 4.10.
1H NMR (CDCl3): d = 1.31 [3 H, t, J = 7.4 Hz, P(O)OCH2CH3],
1.33 [3 H, t, J = 6.8 Hz, P(O)OCH2CH3], 1.60 (3 H, s, CH3), 1.82 (3
H, s, CH3), 2.19 (1 H, dd, JH,P = 18.8 Hz, J = 6.9 Hz, NCHP), 2.71
(1 H, dd, JH,P = 5.6 Hz, J = 6.9 Hz, NCH), 4.20 [4 H, dq, J = 7.3 Hz,
2-Diethylphosphono-1-vinyl-3-(trimethylsilyl)aziridines (20);
General Procedure
A solution of 1-phosphono-2-aza-1,3-diene 14 (2 mmol) in toluene
(10 mL) was placed under N2. (Trimethylsilyl)diazomethane (3
mmol) was added using a syringe and the reaction mixture was
stirred for 48 h under reflux after which the solvent was evaporated
under reduced pressure. The crude reaction mixture was purified by
means of flash chromatography yielding the pure cis-aziridines 20
as yellowish oils.
J
H,P = 1.7 Hz, P(O)OCH2CH3], 5.32 (1 H, d, J = 1.0 Hz, CH).
13C NMR (CDCl3): d = 13.95 (CH3), 16.27 [2 C, d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 16.91 (CH3), 21.85 (CH3), 39.63 (d, JC,P = 216.7
Hz, NCHP), 43.87 (d, JC,P = 5.9 Hz, NCH), 61.28 (OCH2), 62.54 [d,
JC,P = 6.1 Hz, P(O)OCH2CH3], 62.88 [d, JC,P = 6.1 Hz,
P(O)OCH2CH3], 126.63 (Cquat), 133.74 (d, JC,P = 6.1 Hz, CH),
166.92 (C=O).
31P NMR (CDCl3): d = 18.58.
MS: m/z = 305 (11, [M+]), 260 (6), 232 (100), 204 (25), 168 (76),
cis-3-Diethylphosphono-1-(2-methylprop-1-enyl)-2-(trimethyl-
silyl)aziridine (20a)
Synthesized according to the general procedure with phospho-
noazadiene 14a; yield: 0.22 g (36%); yellowish oil; Rf 0.10
[EtOAc–petroleum ether, 2:8 (1% Et3N)].
135 (46), 122 (44), 94 (83), 81 (32).
Anal. Calcd for C13H24NO5P: C, 51.14; H, 7.92; N, 4.59. Found: C,
51.17; H, 7.94; N, 4.60.
IR (neat): 1674 cm–1.
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York

734
B. Vanderhoydonck, C. V. Stevens
PAPER
1H NMR (CDCl3): d = 0.08 [9 H, s, Si(CH3)3], 1.33 [6 H, t, J = 6.9
Hz, P(O)OCH2CH3], 1.59 (3 H, s, CH3), 1.65 (1 H, dd, JH,P = 12.9
Hz, J = 5.3 Hz, NCHSi), 1.77 (3 H, s, CH3), 2.00 (1 H, dd,
JH,P = 22.1 Hz, J = 5.3 Hz, NCHP), 4.13 [4 H, quint, J = 6.9 Hz,
P(O)OCH2CH3], 5.52 (1 H, s, CH).
(CH2), 27.10 (CH2), 27.29 (CH2), 28.21 (CH2), 33.35 (CH2), 33.75
(NCHSi), 36.82 (d, JC,P = 202.9 Hz, NCHP), 62.37 [t, JC,P = 4.8 Hz,
P(O)OCH2CH3], 130.92 (d, JC,P = 7.3 Hz, CH), 132.31 (Cquat).
31P NMR (CDCl3): d = 24.44.
MS: m/z = 345 (96, [M+]), 330 (13), 273 (62), 244 (15), 208 (47),
180 (27), 134 (100), 122 (49), 106 (52), 73 (88).
13C NMR (CDCl3): d = –1.89 [3 C, Si(CH3)3], 16.49 [2 C, t,
JC,P = 4.9 Hz, P(O)OCH2CH3], 16.96 (CH3), 22.10 (CH3), 33.99 (d,
Anal. Calcd for C16H32NO3PSi: C, 55.62; H, 9.34; N, 4.05. Found:
C, 55.57; H, 9.30; N, 4.09.
JC,P = 3.7 Hz, NCHSi), 36.25 (d, JC,P = 202.0 Hz, NCHP), 62.34 [2
C, d, JC,P = 6.1 Hz, P(O)OCH2CH3], 124.85 (Cquat), 133.80 (d,
JC,P = 7.3 Hz, CH).
31P NMR (CDCl3): d = 24.45.
MS: m/z = 305 (55, [M+]), 276 (26), 232 (26), 206 (31), 168 (59),
Acknowledgment
This work was supported by the Belgian IWT (Instituut voor de
Aanmoediging van Innovatie door Wetenschap en Technologie in
Vlaanderen; Institute for the Promotion of Innovation by Science
and Technology in Flanders).
153 (47), 121 (35), 94 (100), 73 (77).
Anal. Calcd for C13H28NO3PSi: C, 51.12; H, 9.24; N, 4.59. Found:
C, 51.21; H, 9.22; N, 4.62.
cis-3-(Diethylphosphono)-1-(2-ethylbut-1-enyl)-2-(trimethylsi-
lyl)aziridine (20b)
References
Synthesized according to the general procedure with phospho-
noazadiene 14b; yield: 0.28 g (42%); yellowish oil; Rf 0.16
[EtOAc–petroleum ether, 3:7 (1% Et3N)].
IR (neat): 1660 cm–1.
(1) Kafarski, P.; Lejczak, B. Phosphorus, Sulfur Silicon Relat.
Elem. 1991, 63, 193.
(2) Aminophosphonic and Aminophophosphinic Acids:
Chemistry and Biological Activity; Kukhar, V. P.; Hudson,
H. R., Eds.; Wiley: Chichester, 2000, ; and references cited
therein.
(3) Christensen, B. G.; Leanza, W. J.; Beattie, T. R.; Patchet, A.
A.; Arison, B. H.; Ormond, R. E.; Kuehl, F. A.; Albers-
Schonberg, G. Jr.; Jardetzky, O. Science 1969, 166, 123.
(4) Giordano, C.; Castaldi, G. J. Org. Chem. 1989, 54, 1470.
(5) Barnes, N. J.; Cox, J. M.; Hawkes, T. R.; Knee, A. J. UK
Patent GB 2280676, 1995; Chem. Abstr. 1995, 123, 83729.
(6) Sietsema, W. K.; Ebetino, F. H. Exp. Opin. Invest. Drugs
1994, 3, 1255.
(7) Arndt, U.; Block, H. D.; Schulz-Schlitte, W. H. Ger. Offen.
DE 3933546, 1991; Chem. Abstr. 1991, 115, 49981.
(8) De Lombaert, S. PCT Int. Appl. WO 9619486, 1996; Chem.
Abstr. 1996, 125, 143011.
1H NMR (CDCl3): d = 0.08 [9 H, s, Si(CH3)3], 0.94 (3 H, t, J = 7.6
Hz, CH3), 0.99 (3 H, t, J = 7.6 Hz, CH3), 1.31 [6 H, m,
P(O)OCH2CH3], 1.63 (1 H, dd, JH,P = 12.5 Hz, J = 5.3 Hz, NCHSi),
1.96 (1 H, dd, JH,P = 22.1 Hz, J = 5.3 Hz, NCHP), 2.21 (2 H, q,
J = 7.0 Hz, CH2), 2.36 (2 H, q, J = 7.0 Hz, CH2), 4.12 [4 H, q,
J = 7.3 Hz, P(O)OCH2CH3], 5.46 (1 H, s, CH).
13C NMR (CDCl3): d = –1.74 [3 C, Si(CH3)3], 12.52 (CH3), 12.70
(CH3), 16.49 [d, JC,P = 3.6 Hz, P(O)OCH2CH3], 16.58 [d, JC,P = 3.6
Hz, P(O)OCH2CH3], 21.69 (CH2), 26.16 (CH2), 33.92 (d, JC,P = 3.7
Hz, NCHSi), 36.69 (d, JC,P = 205.7 Hz, NCHP), 62.30 [2 C, t,
J = 3.6 Hz, P(O)OCH2CH3], 132.89 (d, JC,P = 6.1 Hz, CH), 136.33
(Cquat).
31P NMR (CDCl3): d = 24.31.
MS: m/z = 333 (64, [M+]), 318 (100), 261 (26), 246 (34), 180 (36),
(9) Stevens, C. V.; Verbeke, A.; De Kimpe, N. Synlett 1998,
180.
122 (34), 108 (87), 73 (71).
(10) Rajski, S. R.; Williams, R. M. Chem. Rev. 1998, 98, 2723.
(11) Onys’ko, P. P.; Maidanovich, N. K.; Kim, T. V.; Kiseleva,
E. I.; Sinitsa, A. D. Russ. J. Gen. Chem. 1998, 68, 536.
(12) Stevens, C. V.; Gallant, M.; De Kimpe, N. Tetrahedron Lett.
1999, 40, 3457.
(13) Seyferth, D.; Marmor, R. S.; Hilbert, P. J. J. Org. Chem.
1971, 10, 1379.
(14) Takahashi, H.; Yoshioka, M.; Imai, N.; Onimura, K.;
Kobayashi, S. Synthesis 1994, 763.
Anal. Calcd for C15H32NO3PSi: C, 54.02; H, 9.67; N, 4.20. Found:
C, 54.09; H, 9.63; N, 4.18.
cis-1-(Cyclohexylidenemethyl)-3-diethylphosphono-2-(trimeth-
ylsilyl)aziridine (20c)
Synthesized according to the general procedure with phospho-
noazadiene 14c; yield: 0.30 g (44%); yellowish oil; Rf 0.16
[EtOAc–petroleum ether, 3:7 (1% Et3N)].
IR (neat): 1667 cm–1.
(15) Sainz-Díaz, C. I.; Gálvez-Ruano, E.; Hernández-Laguna, A.;
Bellanato, J. J. Org. Chem. 1995, 60, 74.
(16) Casarrubios, L.; Pérez, J. A.; Brookhart, M.; Templeton, J.
L. J. Org. Chem. 1996, 61, 8358.
(17) Rasmussen, K. G.; Jørgensen, K. A. J. Chem. Soc., Perkin
Trans. 1 1997, 1287.
(18) Xie, W.; Fang, J.; Li, J.; Wang, P. G. Tetrahedron 1999, 55,
12929.
1H NMR (CDCl3): d = 0.08 [9 H, s, Si(CH3)3], 1.31 [6 H, t, J = 7.1
Hz, P(O)OCH2CH3], 1.50 (6 H, m, CH2), 1.61 (1 H, dd, JH,P = 12.5
Hz, J = 5.3 Hz, NCHSi), 1.88 (2 H, m, CH2), 1.95 (1 H, dd,
JH,P = 22.1 Hz, J = 5.3 Hz, NCHP), 2.25 (2 H, m, CH2), 4.11 [4 H,
m, P(O)OCH2CH3], 5.50 (1 H, s, CH).
13C NMR (CDCl3): d = –1.67 [3 C, Si(CH3)3], 16.46 [d, JC,P = 2.5
Hz, P(O)OCH2CH3], 16.55 [d, JC,P = 2.5 Hz, P(O)OCH2CH3], 26.77
Synthesis 2004, No. 5, 722–734 © Thieme Stuttgart · New York