Three-component reaction between trivalent phosphorus, dimethyl acetylenedicarboxylate, and amide derivatives

Article abstract of DOI:10.1080/10426500802625891

Stabilized phosphoranes were synthesized from the reaction between dimethyl acetylenedicarboxylate and amide derivatives in the presence of triphenylphosphine. Dimethylurea containing a phosphorus ylide underwent a smooth reaction in boiling toluene to produce hydantoin and oxo-oxazolidin containing stable phosphorus ylides in good yields. Phosphorus ylides derived from (PhO)₃P were not stable and converted to diastereoisomeric phosphonates and phosphorimidate. The nature of the amide derivatives and type of trivalent phosphorus compounds, as well as solvents, determined the distribution of products.

Full text of DOI:10.1080/10426500802625891

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Three-Component Reaction
Between Trivalent
Phosphorus, Dimethyl
Acetylenedicarboxylate, and
Amide Derivatives
Nader Zabarjad-Shiraz a , Issa Yavari b , Azizolah
Biglari a , Seyed Ahmad Izadiar a & Hamid-Reza
Bijanzadeh b
a Department of Chemistry, Islamic Azad University,
Central Tehran Branch, Tehran, Iran
b Department of Chemistry, Tarbiat Modares
University, Tehran, Iran
Published online: 03 Nov 2009.
To cite this article: Nader Zabarjad-Shiraz , Issa Yavari , Azizolah Biglari , Seyed
Ahmad Izadiar & Hamid-Reza Bijanzadeh (2009) Three-Component Reaction Between
Trivalent Phosphorus, Dimethyl Acetylenedicarboxylate, and Amide Derivatives,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:11, 3023-3037, DOI:
10.1080/10426500802625891
To link to this article: http://dx.doi.org/10.1080/10426500802625891
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Phosphorus, Sulfur, and Silicon, 184:3023–3037, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802625891
Three-Component Reaction Between Trivalent
Phosphorus, Dimethyl Acetylenedicarboxylate,
and Amide Derivatives
Nader Zabarjad-Shiraz,1 Issa Yavari,2 Azizolah Biglari,1
Seyed Ahmad Izadiar,1 and Hamid-Reza Bijanzadeh2
1Department of Chemistry, Islamic Azad University, Central Tehran
Branch, Tehran, Iran
2Department of Chemistry, Tarbiat Modares University, Tehran, Iran
Stabilized phosphoranes were synthesized from the reaction between dimethyl
acetylenedicarboxylate and amide derivatives in the presence of triphenylphos-
phine. Dimethylurea containing a phosphorus ylide underwent a smooth reaction
in boiling toluene to produce hydantoin and oxo-oxazolidin containing stable phos-
phorus ylides in good yields. Phosphorus ylides derived from (PhO)3P were not
stable and converted to diastereoisomeric phosphonates and phosphorimidate. The
nature of the amide derivatives and type of trivalent phosphorus compounds, as
well as solvents, determined the distribution of products.
Keywords β-Amidophosphonates; hydantoin; oxo-oxazolidin; stable phosphorus ylides;
phosphorimidate; three-component reaction
INTRODUCTION
Organophosphorus compounds are important substrates in the study
of biochemical processes.1,2 For a long time, phosphorus analogues
of amino acids, in which the carboxylic acid group is replaced
with phosphonate group, P(O)(OR)2, have attracted particular inter-
est in preparing analogues of numerous natural products.3,4 In this
area, β-amido phosphonates as isosteres of β-amino acids occupy an
important place and reveal diverse and interesting biological and
biochemical properties.5,6 There are several methods for synthesis of β-
amidophosphonates. In most of them, nucleophilic trivalent phosphorus
is attached to an electrophilic carbon.7
Received 30 July 2008; accepted 11 November 2008.
Address correspondence to Nader Zabarjad-Shiraz, Department of Chemistry, Islamic
Azad University, Central Tehran Branch, Sanat Sq., Tehran, Iran. E-mail: zabarjad
sh@yahoo.com
3023

3024
N. Zabarjad-Shiraz et al.
Multicomponent reactions have proven highly efficient in the assem-
bly of diversified molecules.8 Among the methods available for hetero-
cyclic synthesis, the generation of 1,3-dipolar species and their trapping
by suitable π systems leading to five-membered heterocycles occupies
a prime position.9 Zwitterionic species often result from the addition of
nucleophiles to activated alkynes. Triphenylphosphine (Ph3P) has been
the most studied nucleophilic species.10
Considering these strategies and importance of multicomponent re-
actions in organic synthesis, as a part of our study on the devel-
opment of new routes to heterocycles and organophosphorus com-
pounds,11 we now report on the reaction of (PhO)3P and/or Ph3P and
dimethyl acetylenedicarboxylate (DMAD, 2) in the presence of amides
and/or N,Nꢀ-dimethylurea to produce β-amidophosphonates, phospho-
nates, and stable phosphorus ylides.
RESULTS AND DISCUSSION
The reaction of 2 and N,Nꢀ-dimethylurea 3a in the presence of
triphenylphosphine 1a in dried CH2Cl2 as solvent and at ambi-
ent temperature proceeded to produce directly hydantoin and oxo-
oxazolidin containing stable phosphorus ylides 5 and 6 in good yields
(Schemes 1 and 2).
Usually the solubility of phosphorus ylides in ethyl acetate is less
than in methylenechloride. So for restricting the reaction, ethyl acetate
was used as a solvent. The reaction was complete in EtOAc within a
few hours. Precipitation of phosphoranes 4 in ethylacetate prevents the
reaction proceeding to produce phosphorus ylides 5 and 6. 1H, 13C, and
31P NMR spectra of these crude products clearly showed the formation
CO2Me
O
O
R'
C
+
R
N
EtOAc
R"3P
R'
+
Products
CO2Me
N
H
R
C
Reflux
MeO2C
CO2Me
PR"3
1
a
b
R"
Ph
OPh
2
4
3
a
b
c
R-
R'
MeNH- CH3
CH3 -
Ph-
H
H
H
d
N
SCHEME 1

Three-Component Reaction
3025
Me
CO2Me
O
N
O
Me
Me
C
+
C
CH2Cl2
r.t.
H
N
N
H
(C6H5)3P
+
N
N
Me
N
O
+
CO2Me
P(C6H5)3
CO2Me
P(C6H5)3
Me
Me
CO2Me
O
O
6
2
3a
1a
5
SCHEME 2
of stable phosphorus ylide 4 in good yields (Scheme 2). No product other
than 4 could be detected. Phosphorane 4 undergoes a smooth reaction
in boiling toluene to produce a mixture of stable phosphorus ylides 5
and 6 (Scheme 3). Ylides 5 and 6 were stable in boiling toluene.
The reaction of 2 with amides 3b–3d in the presence of 1a at r.t.
in ethyl acetate and/or methylenechloride was complete within a few
1
hours. H, 13C, and 31P NMR spectra of these crude products showed
the formation of stable phosphorus ylides 7 in good yields (Scheme 4).
No other product than 7 could be detected.
Structures of ylides 4a–4d were deduced from their IR, 1H, 13C, and
31P NMR spectra. The mass spectra of these compounds display molec-
ular ion peaks. In spite of ylide 4a, IR do not show N-H stretching
1
absorption for 5 and 6. H and 13C NMR of 4a showed four peaks for
1
NCH3 and four peaks for OCH3 groups. H and 13C NMR spectra of 5
and 6 show eight NCH3 and 4 OCH3 groups. Resonance of C=N-CH3
protons of 6 appeared at about 2.3 ppm, which is in downfield in com-
parasion with resonance of C-N-CH3 protons of 5 (see the Experimental
section). These comparisions indicated that during formation of phos-
phoranes 5 and 6 from 4a, H-atom of N-H have been eliminated by one
of OMe groups of esters as MeOH (Scheme 3).
1H, 13C, and 31P NMR spectra of ylides 4, 5, and 6 are consistent with
the presence of two diastereoisomers. The ylide moiety of these com-
pounds is strongly conjugated with the adjacent carbonyl group and
rotation around the partial double bond in the (E) and (Z) geometrical
isomers (Scheme 5). Rotation is slow on the NMR time scale at ambient
O
CO2R
O
Me
C
+
MeHN
MeO2C
Toluene
Reflux
N
EtOAc
r.t.
Me
Me
(C6H5)3P
+
5 + 6
CO2Me
N
H
N
H
C
CO2R
P(C6H5)3
4a
2
1a
3a
SCHEME 3

3026
N. Zabarjad-Shiraz et al.
O
CO2Me
O
EtOAc
C
+
R
NH
(C6H5)3P
+
CO2Me
NH2
R-
R
C
MeO2C
CO2Me
P(C6H5)3
R-
CH3 -
1a
4
b
2
3
b
CH3 -
c
d
Ph-
c
d
Ph-
N
N
SCHEME 4
1
temperature. Selected H, 13C, and 31P NMR chemical shifts and cou-
pling constants in the major (M) and minor (m) geometrical isomers of
compounds 4, 5, and 6 are shown in the Experimental section.
Phosphorus ylides 4b–4d are stable in boiling toluene, although the
ylides derived from the reaction of ureas, instead of amides, led to
the production of iminophosphoranes in the same conditions.12 In the
presence of H2O in boiling toluene, phosphorus ylides were decomposed
to triphenylphosphine oxide, Ph3P=O.
The reaction of 2 with 3a in the presence of triphenyl phosphite 1b at
r.t. in EtOAc was complete within 1 day. 1H, 13C, and 31P NMR spectra
of these crude products clearly showed the formation of phosphonate 7
and phosphorimidate 8 in good yields (Scheme 6). The structures of 7
1
and 8 were deduced from their IR, H, 13C, and 31P NMR spectra. The
mass spectra of these compounds display molecular ion peaks.
When the reaction was carried out in EtOAc, 31P NMR showed three
peaks for the crude products. The peak at –11.29 ppm is proof for the
formation of a phosphorimidate (8, (PhO)3P=N) structure, and two
peaks at 11.98 and 12.67 ppm indicate two phosphonate structures
(7, C-P(=O)(OPh)2). In dried CH2Cl2, the peaks of two phosphonates
disappeared in 31P NMR.
The products were isolated and their structures were elucidated from
their NMR spectra. 1H NMR of 8 indicates no signal for methyl groups
of esters at 3–4 ppm. This is in agreement with the elimination of
dimethyl fumarate and/or dimethyl maleate 18 and the formation of
phosphorimidate 8. 13C and 31P NMR spectra of 8 confirmed the phos-
phorimidate structure. The 1H NMR spectra of phosphonates 7 display
signals for vicinal methine protons at δ = 4.22–5.62 ppm, which appear
2
3
as doublet of doublets for each isomer with JPH = 23.8, JPH = 18.0,

Three-Component Reaction
3027
O
O
R
N
R'
R
N
R'
OMe
O
MeO2C
(C6H5)3P
MeO2C
+
+
O
OMe
(C6H5)3P
(E)-4 ; Minor
(Z)-4; Major
O
O
Me
N
Me
Me
Me
N
N
N
OMe
O
O
O
O
+
+
OMe
(C6H5)3P
(C6H5)3P
(Z)-5; Major
(E)-5 ; Minor
Me
O
Me
O
N
N
Me
Me
N
N
OMe
O
OMe
O
O
+
+
O
(C6H5)3P
(C6H5)3P
(Z)-6; Major
(E)-6; Minor
SCHEME 5
O
CO2Me
O
O
C
C
H3C
MeO2C
NH
+
(PhO)3P
+
CO2Me
+
NH2
H3C
N
P(OPh)3
H3C
OPh
OPh
CO2Me
P
O
3b
8
1b
7
2
SCHEME 6

3028
N. Zabarjad-Shiraz et al.
O
O
NHCOCH3
H
NHCOCH3
(PhO)2P
H3CO2C
CO2CH3
(PhO)2P
CO2CH3
H
H3CO2C
H
H
7 ( 2R,3R) or (2S,3S)
7 ( 2R,3S) or (2S,3R)
SCHEME 7
3
2
and JHH = 5.6 Hz for (2R, 3S) or (2S, 3R)-7 isomer, and JPH = 24.0,
3JPH = 9.0, and 3JHH = 3.5 Hz for (2R, 3R) or (2S, 3S)-7 isomer.
The presence of 31P nucleus in compounds 7 contributes in the as-
signment of signals by coupling with 1H and 13C nuclei (see the Experi-
mental section). The vicinal proton–proton coupling constant (3JHH) as
a function of the torsion angle can be obtained from the Karplus equa-
tion.13 Typically, 3Jgauche varies between 1.5–6.0 Hz, and 3Janti between
10–16 Hz. The observation of 3JHH = 3.5 and 5.6 Hz for vicinal protons
in the two isomers of 7 indicates a gauche arrangment for this protons.
3
The three-bond carbon-phosphorus coupling, JPC, depends on the
configuration, and as expected, transoid couplings are larger than cisoid
ones. The Karplus relation can be derived from the data for organophos-
phorus compounds with tetra- and pentavalent phosphorus.14 The ob-
3
servation of JPC = 4 Hz is in agreement with a cisoid arrangement
of P with C=O of ester. 3JPC = 22 Hz indicated transoid arrangement,
which was in agreement with (2R,3R) or (2S, 3S) configuration for an-
other isomer (Scheme 7).
Although we have not yet established the mechanism of the for-
mation of ylides 4, 5, and 6, on the basis of chemistry of trivalent
phosphorus nucleophiles,15 it is reasonable to assume that phosphorus
ylides 4 resulted from the initial addition of trivalent phosphorus 1 to
the acetylenic ester 2. Subsequent protonation of the 1:1 adduct was
followed by attacking the nitrogen atom of the anion of NH-acid 9 on
the vinylphosphonium cations 10 to generate ylides 4 (Scheme 8).
O
CO2Me
O
O
+
R'
R"3P
C
+
C
R
N
R" P
+
R'
3
+
NR'
C
CHCO2CH3
CO2Me
R
N
H
R
MeO2C
MeO2C
CO2Me
PR"3
10
4
2
3
1
9
SCHEME 8

Three-Component Reaction
3029
O
O
Me
Me
Me
OMe
N
N
H
N
CO2Me
H
Me
Me
N
5
MeO
CO2Me
- MeOH
O
+
Me
+
P(C6H5)3
+
Me
Me
O
O
P(C6H5)3
O
N
N
H
CO2Me
13
11
P(C6H5)3
O
N
4a
Me
H
Me
Me
OMe
CO2Me
N
N
N
6
H
CO2Me
O
-MeOH
MeO
+
+
P(C6H5)3
O
P(C6H5)3
O
14
12
SCHEME 9
In boiling toluene or in dried CH2Cl2, the NH-proton of 4a shifted
to the ylinic carbon and formed the 1,6-diionic compounds 11 and 12.
These diionic intermediates underwent an intramolecular nucleophilic
substitution by attacking the N− or O− nucleophile on the ester groups
and led to the formation of intermediates 13 and 14. Deprotonation by
MeO−, led to the formation of ylides 5 and 6 (Scheme 9).
In the presence of moisture, H2O attacked the phosphorus atom of 4
and produced intermediate 15, which underwent PhOH elimination to
form phosphonate 8 (Scheme 10).
Alternatively in dry solvent, the NH-proton of 4 shifted to the ylidic
carbon and formed the betain 16, which could be in equilibrium with
azaphosphetane 17. Formation of dimethyl fumarate and/or dimethyl
maleate 18 confirmed the proposed mechanism (Scheme 11).
In conclusion, the present method features the advantages that the
reaction can be performed under neutral conditions, and the start-
ing materials and reagents can be mixed without any modifications.
O
O
H
H
H
_
+
H3C
N
H
O
H2O
+
H3C
MeO2C
N
OPh
OPh
P(OPh)3
8
_
P
MeO2C
OPh
CO2Me
CO2Me
15
4
SCHEME 10

3030
N. Zabarjad-Shiraz et al.
O
O
_
N
O
H
_
H3C
MeO2C
N
N
H3C
P(OPh)3
CO2Me
+
H3C
MeO2C
+
P(OPh)3
P(OPh)3
MeO2C
CO2Me
O
CO2Me
17
16
4
MeO2CCH CHCO2Me
+
P(OPh)3
N
H3C
8
18
SCHEME 11
Phosphorus ylides can be considered as potentially useful synthetic
intermediates.
Phosphorus ylides derived from triphenylphosphites are not stable
and undergo reactions to produce phosphonates and phosphorimidates.
The presence or absence of H2O plays an important role in formation
of phosphonates and/or phosphorimidates.
Phosphorus ylides containing additional reactive functional groups,
such as N-H, are potentially able to undergo further intramolecular
reaction to produce other compounds.
Although three component reactions between trivalent phosphorus,
acetylenic esters, and N-H acids are well studied, the prediction of the
final product is complicated, and should be considered by attention to
the solvent, temperature, presence or absence of moisture, and type of
solvent, as well as the functionality of starting materials.
The procedure described here provides an acceptable method for
preparation of phosphorus ylides, phosphorimidates, and phosphonates
as well as some heterocycle-containing phosphoranes.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus.
Elemental analyses for C, H, and N were performed using a Heraeus
CHN-O-Rapid analyzer. These data were in good agreement with the
calculated values. IR spectra were measured on a Shimadzu IR 460
1
spectrometer. H and 13C NMR spectra were measured with Bruker
DRX-500 Avance spectrometer at 500.1 MHz and 125.8 MHz, respec-
tively. Mass spectra were recorded with a Finnigan-Matt 8430 mass
spectrometer operating at an ionization potential of 70 eV. Triph-
enylphosphine, triphenylphosphite, N,Nꢀ-dimethylurea, DMAD, and

Three-Component Reaction
3031
amides were purchased from Fluka (Buchs, Switzerland) and were used
without further purification.
Typical Process for the Preparation of Dimethyl
2-(1,3-dimethyl-ureido)-3-triphenylphosphanylidene)
succinate 4a
To a magnetically stirred mixture of N,Nꢀ-dimethylurea (0.24 g, 2 mmol)
and triphenylphosphine (0.52 g, 2 mmol) in EtOAc (10 mL), a solution
of DMAD (0.14 g, 2 mmol) in EtOAc (3 mL) was added dropwise. The
solution was stirred at r.t. for 24 h. The solvent was removed under
reduced pressure, and the solid residue was washed with cold diethyl
ether (2 × 5 mL), and the product was obtained as colorless crystals. IR
(KBr) (νmax, cm−1) 3320 (NH), 1750 (C=O), 1695 (NC=O), 1630 (C=C).
Analyses: Calcd. for C27H29N2O5P (492.5): C, 65.85; H, 5.94; N, 5.69%.
Found: C, 65.8; H, 5.9; N, 5.8%. 1H, 13C, 31P NMR data for major isomer
3
(67%) (Z)-4a. 1H NMR (500.1 MHz, CDCl3): δ 2.61 (3H, d, JHH = 4.2
Hz, NHCH3), 2.84 (3H, s, NCH3), 3.08 and 3.73 (6H, 2s, 2 OCH3), 4.21
(1H, bs, CH), 4.62 (1H, bs, NH), 7.4–7.8 (15 H, m, 3 C6H5). 13C NMR
(125.8 MHz, CDCl3) δ 27.2 and 31.1 (2 NCH3), 41.3 (d, 1JPC = 129 Hz,
P-C = C), 49.1 and 52.2 (2 OCH3), 59.2 (d, 2JPC = 17.6 Hz, CH), 126.7
(d, 1JPC = 92 Hz, P-Cipso), 128.8 (d, 3JPC = 12 Hz, Cmeta), 132.1 (d, 4JPC
= 2 Hz, Cpara), 133.5 (d, 2JPC = 10 Hz, Cortho), 158.5 (NC=O), 160.3 (P-C
4
= C), 170.1 (d, JPC = 13.0 Hz, OC=O). 31P NMR (202.4 MHz, CDCl3)
δ 24.72 (Ph3P+-C).
1H, 13C, 31P NMR data for minor isomer (33%) (E)-4a: 1H NMR (500.1
MHz, CDCl3): δ 2.64 (3H, d, 3JHH = 4.5 Hz, NHCH3), 2.94 (3H, s, NCH3),
3.51 and 3.69 (6H, 2s, 2 OCH3), 4.68 (1H, d, 3JPH = 16 Hz, CH), 5.24
(1H, bs, NH), 7.4–7.8 (15 H, m, 3 C6H5). 13C NMR (125.8 MHz, CDCl3) δ
26.8 and 29.4 (2 NCH3), 41.7 (d, 1JPC = 131 Hz, P-C = C), 51.9 and 52.3
(2 OCH3), 57.9 (d, 2JPC = 17 Hz, CH), 126.1 (d, 1JPC = 92 Hz, P-Cipso),
3
4
128.5 (d, JPC = 12 Hz, Cmeta), 131.9 (d, JPC = 2 Hz, Cpara), 133.4 (d,
2JPC = 10 Hz, Cortho), 158.5 (NC=O), 164.0 (P-C = C), 173.7 (d, 4JPC
17 Hz, OC=O). 31P NMR (202.4 MHz, CDCl3) δ 25.26 (Ph3P+-C).
=
Dimethyl 2-(Triphenylphosphonylidene)-3-
acetamidosuccinate (4b)
White powder. Mp 142–144◦C. IR (KBr) (νmax, cm−1) 3448 (N-H), 1747
(C=O), 1648 (C=O). MS (EI, 70 eV): m/z (%) = 464 (M+, 4), 262 (100).
Anal Calcd for C26H26NO5P (463.5): C, 67.38; H. 5.65; N, 3.02. Found:
C, 67.5; H. 5.7; N, 3.1.

3032
N. Zabarjad-Shiraz et al.
1
1H, 13C, and 31P NMR data for the major (72%) (Z)-4b: H NMR
(500.1 MHz, CDC13) δ : 1.96 (3H, s, CH3), 3.14 and 3.69 (6H, 2s, 2
OCH3), 4.5.7 (1H, dd, 3JHH = 8.3 Hz, 3JPH = 15.1 Hz, CH), 7.40 (1H, d,
3JHH = 8.3 Hz, NH), 7.57.7 (15 H, m, 3 C6H5). 13C NMR (125.8 MHz,
CDCl3) δ : 23.3 (CH3), 43.5 (d, 1JPC = 128 Hz, P-C = C), 49.0 and 52.2 (2
OCH3), 51.5 (d, 2JPC = 17.8 Hz, CH), 126.6 (d, 1JPC = 92.4 Hz, P-Cipso),
3
4
128.5 (d, jPC = 12.2 Hz, Cmeta), 132.1 (d, JPC = 2Hz, Cpars), 133.8 (d,
2JPC = 10 Hz, Cortho), 168.7 (NC=O), 170.4 (d, JPC = 12.8 Hz, C =
2
C-O), 173.8 (d, JPC = 8 Hz, C=O). 31P NMR (202.4 MHz, CDCl3) δ :
3
22.32 (Ph3P+-C).
1H, 13C, and 31P NMR data for the minor (28%) (E)-4b: H NMR
1
(500.1 MHz, CDCl3) δ 1.96 (3H, s, CH3), 3.57 and 3.69 (6 H, 2 s, 2
3
OCH3), 4.58 (1H, dd, JHH = 8.4 Hz, NH), 7.5–7.7 (15 H, m, 3 C6H5).
1
13C NMR (125.8 MHz, CDCl3) δ : 23.3 (CH3), 44.1 (d, JPC = 132 Hz,
P-C = C), 50.1 and 50.9 (2 OCH3), 51.5 (d, 2JPC = 17.8 Hz, CH), 126.0
1
3
(d, JPC = 93.3 Hz, P-Cipso), 128.7 (d, JPC = 12 Hz, Cmeta), 132.1 (d,
4JPC = 2 Hz, Cpara), 133.8 (d, 2JPC = 10 Hz, Cortho), 168.7 (NC=O), 170.4
2
3
(d, JPC = 12.8 Hz, C = C-O), 173.8 (d, JPC = 8 Hz, C=O). 31P NMR
(202.4 MHz, CDC13) δ : 22.32 (Ph3P+-C).
Dimethyl 2-(Triphenylphosphonylidene)-3-
(benzamido)succinate (4c)
White powder. Mp 192–194◦C IR (KBr) (νmax, cm−1) 3404 (N-H), 1744
(C=O), 1702 (C=O). MS (EI, 70 eV): m/z (%) = 525 (M+, 6), 262 (100).
Anal Calcd for C31H28NO5P (463.5): C, 70.85; H. 5.37; N, 2.67. Found:
C, 70.38; H. 5.4; N, 2.7.
1H, 13C, and 31P NMR data for the major (81%) (Z)-4c: 1H NMR (500.1
MHz, CDC13) δ 3.14 and 3.68 (6H, 2s, 2OCH3), 4.80 (1 H, dd, 3JHH = 8.5
Hz, 3JPH = 13.9 Hz, CH), 8.30 (1H, d, 4JHH = 8.5 Hz, NH), 7.4–7.8 (20
1
H, m, 4 C6H5).13C NMR (125.8 MHz, CDCl3) δ 43.3 (d, JPC = 128 Hz,
2
P-C = C), 49.0 and 52.2 (2 OCH3), 52 (d, JPC = 17.2 Hz, CH), 127 (d,
3
4
1JPC = 129 Hz, P-Cipso), 128.6 (d, JPC = 9.2 Hz, Cmeta), 132.1 (d, JPC
= 16 Hz, Cpars), 133.8 (d, 2JPC = 10 Hz, Cortho), 166.1 (NC=O), 170.5 (d,
4JPC = 12.8 Hz, C = C-O), 173.8 (d, 3JPC = 8 Hz, C=O). 31P NMR (202.4
MHz, CDCl3) δ 21.66 (Ph3P+-C).
1H, 13C and 31P NMR data for the minor (19%) (E)-4c.1H NMR (500.1
3
MHz, CDCl3) δ 3.60 and 3.7 (6 H, 2s, 2 OCH3), 4.81 (1 H, dd, JHH
=
6.1 Hz, NH), 7.4–7.8 (20 H, m, 4 C6H5). 13C NMR (125.8 MHz, CDCl3)
δ 44.1 (CH3), 44.1 (d, 1JPC = 132 Hz, P-C = C), 50.2 and 51.4 (2 OCH3),
50.9 (d, 2JPC = 16 Hz, CH), 126.3 (d, 1JPC = 67.3 Hz, P-Cipso), 128.5 (d,
3JPC = 12.6 Hz, Cmeta), 132.1 (d, JPC = 15.9 Hz, Cpara), 133.8 (d, JPC
4
2

Three-Component Reaction
3033
2
= 10 Hz, Cortho), 166.1 (NC=O), 170.4 (d, JPC = 12.8 Hz, C = C-O),
3
173.8 (d, JPC = 8 Hz, C=O). 31P NMR (202.4 MHz, CDC13) δ : 22.32
(Ph3P+-C).
Dimethyl 2-(Triphenylphosphonylidene)-3-
(nicotinamido)succinate (4d)
White powder. Mp 175–177◦C. IR (KBr) (νmax, cm−1) 3367 (N-H), 1698
(C=O), 1620 (C=O). MS (EI, 70 eV): m/z (%) = 526 (M+, 4), 262 (100).
Anal Calcd for C31H28NO5P (526.5): C, 68.43; H. 5.17; N, 5.32. Found:
C, 68.3; H. 5.2; N, 5.4.
1
1H, 13C, and 31P NMR data for the major (75%) (Z)-4d: H NMR
(500.1 MHz, CDC13) δ 3.13 and 3.68 (6 H, 2 s, 2 OCH3), 4.74 (1 H, dd,
3
4
3JHH = 8.9 Hz, JPH = 14 Hz, CH), 7.30 (1H, d, JHH = 9 Hz, NH),
7.5–7.7 (20 H, m, 4 C6H5). 13C NMR (125.8 MHz, CDCl3) δ 43.1 (d, 1JPC
2
= 128 Hz, P-C = C), 49.1 and 52.3 (2 OCH3), 52.2 (d, JPC = 18.5 Hz,
CH), 150.5 (d, 1JPC = 443 Hz, P-Cipso), 164.3 (d, 3JPC = 12.6 Hz, Cmeta)
,
4
2
170.6 (d, JPC = 12.6 Hz, Cpars), 173.5 (d, JPC = 7 Hz, Cortho), 123.2
4
3
(NC=O), 128.7 (d, JPC = 12.2 Hz, C = C-O), 133.8 (d, JPC = 9.8 Hz,
C=O). 31P NMR (202.4 MHz, CDCl3) δ : 21.66 (Ph3P+-C).
1H, 13C, and 31P NMR data for the minor (25%) (E)-10c: H NMR
1
(500.1 MHz, CDCl3) δ 3.58 and 3.68 (6 H, 2s, 2 OCH3), 4.75 (1 H, dd,
3JHH = 8.7 Hz, 3JPH = 13.3 Hz, CH), 7.26 (1 H, d, 3JHH = 8.7 Hz, NH),
7.5–7.7 (20 H, m, 4 C6H5). 13C NMR (125.8 MHz, CDCl3) δ 44.1 (d, 1JPC
2
= 132 Hz, P-C = C), 50.2 and 51.3 (2 OCH3), 52.2 (d, JPC = 18.5 Hz,
1
3
CH), 150 (d, JPC = 4.7 Hz, P-Cipso), 164.2 (d, JPC = 12.2 Hz, Cmeta),
4
2
170.6 (d, JPC = 12.6 Hz, Cpara), 173.5 (d, JPC = 7 Hz, Cortho), 123.2
2
3
(NC=O), 128.7 (d, JPC = 12.2 Hz, C = C-O), 133.8 (d, JPC = 9.8 Hz,
C=O). 31P NMR (202.4 MHz, CDC13) δ 22.32 (Ph3P+-C).
The Typical Processes for the Preparation of 5 and 6
In the first method, to a magnetically stirred mixture of 3a (0.24 g, 2
mmol) and 1a (0.52 g, 2 mmol) in dried methylene chloride (10 mL), a
solution of DMAD (0.14 g, 2 mmol) in methylene chloride (2 mL) was
added dropwise. The solution was stirred at room temperature for 24
h. The solvent was removed under reduced pressure, the solid residue
was washed with cold diethyl ether (2 × 5 mL), and the products were
obtained as a white powder.
In the second method, a magnetically stirred mixture of phosphorane
4a (0.49 g, 1 mmol) in toluene (30 mL) was refluxed for 12 h. The solvent
was removed under reduced pressure, the solid residue was washed

3034
N. Zabarjad-Shiraz et al.
with cold diethyl ether (2 × 5 mL), and the product was obtained as a
white powder. In both methods the ratio of 5:6 was 55:45.
Methyl 1,3-Dimethyl-2,5-dioxo-imidazolidine-4-
yl)triphenylphosphanilidene)acetate 5
White powder. IR (KBr) (νmax, cm−1): 1749 and 1690 (C=O), 1628 (C=C).
Analyses: Calcd. for C25H23N2O4P (446.40): C, 67.26; H, 5.19; N, 6.27%.
Found: C, 67.3; H, 5.2; N, 6.3%. 1H, 13C, 31P NMR data for major isomer
1
(73%) (Z)-5: H NMR (500.1 MHz, CDCl3): δ 2.94 and 2.98 (6 H, 2s, 2
NCH3), 3.15 (3 H, s, OCH3), 3.46 (1H, d, 3JPH = 35.2 Hz, CH), 7.4–7.8
(15 H, m, 3 C6H5). 13C NMR (125.8 MHz, CDCl3) δ 24.2 and 26.6 (2
1
2
NCH3), 35.3 (d, JPC = 130 Hz, P-C = C), 49.5 (CH3), 61.7 (d, JPC
=
1
3
17 Hz, CH), 125.8 (d, JPC = 92 Hz, P-Cipso), 128.5 (d, JPC = 12 Hz,
4
2
Cmeta), 132.1 (d, JPC = 2 Hz, Cpara), 133.7 (d, JPC = 10 Hz, Cortho),
156.8 (N(C=O)N), 168.6 (d, 2JPC = 13 Hz, P-C = C), 176.0 (d, 3JPC = 5
Hz, NC=O). 31P NMR (202.4 MHz, CDCl3) δ 20.95 (Ph3P+-C).
1H, 13C, 31P NMR data for minor isomer (27%) (E)-5. 1H NMR (500.1
MHz, CDCl3) δ 2.95 and 3.01 (6 H, 2s, 2 NCH3), 3.12 (3 H, s, OCH3),
3.52 (1 H, d, 3JPH = 35.8 Hz, CH), 7.4–7.8 (15 H, m, 3 C6H5). 13C NMR
(125.8 MHz, CDCl3) δ 24.2 and 27.1 (2 NCH3), 36.7 (d, 1JPC = 127 Hz,
2
1
P-C = C), 50.5 (CH3), 62.8 (d, JPC = 18 Hz, CH), 126.7 (d, JPC = 92
Hz, P-Cipso), 129.0 (d, 3JPC = 12 Hz, Cmeta), 132.1 (d, 4JPC = 2 Hz, Cpara),
2
2
133.7 (d, JPC = 10 Hz, Cortho), 156.8 (N(C=O)N), 170.3 (d, JPC = 17
Hz, P-C = C), 175.8 (d, JPC = 5 Hz, NC=O). 31P NMR (202.4 MHz,
3
CDCl3) δ 20.24 (Ph3P+-C).
Methyl (3-Methyl-2-methylimino-4-oxo-oxazolidin-5-yl)-
(triphenylphosphanilidene)acetate 6
IR (KBr) (νmax, cm−1): 1749 and 1690 (C=O), 1628 (C=C). Analyses:
Calcd. for C25H23N2O4P (446.40): C, 67.26; H, 5.19; N, 6.27%. Found:
C, 67.3; H, 5.2; N, 6.3%. 1H, 13C, 31P NMR data for major isomer (70%)
(Z)-6: 1H NMR (500.1 MHz, CDCl3): δ 2.23 and 2.79 (6 H, 2 s, 2 NCH3),
3.42 (3 H, s, OCH3), 5.62 (1 H, d, 3JPH = 30.6 Hz, CH), 7.4–7.8 (15 H, m,
3 C6H5). 13C NMR (125.8 MHz, CDCl3) δ 24.6 and 26.8 (2 NCH3), 37.8
1
2
(d, JPC = 138 Hz, P-C = C), 50.1 (CH3), 63.0 (d, JPC = 12 Hz, CH),
125.8 (d, 1JPC = 92 Hz, P-Cipso), 128.9 (d, 3JPC = 12 Hz, Cmeta), 132.1 (d,
4JPC = 2 Hz, Cpara), 133.7 (d, 2JPC = 10 Hz, Cortho), 155.3 (C=N), 171.3
2
4
(d, JPC = 13 Hz, P-C = C), 174.5 (d, JPC = 2 Hz, OC=O). 31P NMR
(202.4 MHz, CDCl3) δ 23.51 (Ph3P+-C).
1H, 13C, 31P NMR data for minor isomer (30%) (E)-6: 1H NMR (500.1
MHz, CDCl3) δ 2.23 and 2.77 (6 H, 2 s, 2 NCH3), 3.56 (3 H, s, OCH3),

Three-Component Reaction
3035
3.47 (1 H, d, 3JPH = 31.0 Hz, CH), 7.4–7.8 (15 H, m, 3 C6H5). 13C NMR
(125.8 MHz, CDCl3) δ 24.7 and 26.9 (2 NCH3), 36.7 (d, 1JPC = 127 Hz,
2
1
P-C = C), 50.5 (CH3), 62.2 (d, JPC = 11 Hz, CH), 126.7 (d, JPC = 92
Hz, P-Cipso), 128.9 (d, 3JPC = 12 Hz, Cmeta), 132.3 (d, 4JPC = 2 Hz, Cpara),
2
2
133.8 (d, JPC = 10 Hz, Cortho), 155.1 (C=N), 171.4 (d, JPC = 17 Hz,
P-C = C), 174.4 (d, 4JPC = 2 Hz, OC=O). 31P NMR (202.4 MHz, CDCl3)
δ 22.77 (Ph3P+-C).
The Procedure for the Preparation of 7 and 8
A magnetically stirred mixture of 3b (0.24 g, 2 mmol) and 1b (0.52 g,
2 mmol) in EtOAc (10 mL) was added dropwise to a solution of DMAD
(0.14 g, 2 mmol) in EtOAc. The solution was stirred at room temperature
for 24 h. The solvent was removed under reduced pressure, the solid
residue was washed with cold diethyl ether (2 × 5 mL), and the product,
(2S,3R) or (2R,3S)-(7), was obtained as white powder. The residue of
filtrate on silicagel column was washed by 1:1 ethyl acetae:diethyl ether,
was separated to (2S,3S) or (2R, 3R)-7 and 8. When the reaction was
carried out in dried methylene chloride, only phosphorimidate 8 was
isolated as a white powder.
(2S,3R) or (2R,3S)-Dimethyl
2-Acetamido-3-(diphenoxyphosphoryl)succinate (7)
IR (KBr) (νmax, cm−1) 3302 (NH), 1738 (C=O), 1630 (C=C), 1284
(P=O). MS (EI, 70 eV): m/z (%) = 453 (M+, 5), 233 (100). Anal Calcd
for C20H22NO8P (435.4): C, 55.18; H. 5.09; N, 3.22. Found: C, 55.2; H.
1
5.1; N, 3.2. H NMR (500.1 MHz, CDCl3) δ: 1.91 (3 H, s, O = C-CH3),
3.67 and 3.74 (6 H, 2 s, 2 OCH3), 4.22 (1 H, dd, 2JPH = 23.8 Hz, 3JHH
3
3
3
= 5.6 Hz, CH-P), 5.26 (1 H, ddd, JPH = 18 Hz, JHH = 5.6 Hz, JNH
3
= 7.9 Hz, N-CH), 6.78 (1H, d, JHH = 7.9Hz, NH), 7.1–7.3 (10 H, m, 2
OPh). 13C NMR (125.8 MHz, CDCl3)δ: 22.9 (O = C-CH3), 47.0 (d, JPC
1
2
= 138 Hz, P-C), 51.1 (d, JPC = 4 Hz, N-CH), 53.1 and 53.2 (2 OCH3),
3
3
120.3 (d, JPC = 4 Hz, Cortho) 120.5 (d, JPC = 4 Hz, Cortho), 125.5 and
125.7 (2 Cpara), 129.8 and 129.9 (2 Cmeta), 149.9 (d, 2JPC = 9.0 Hz, Cipso),
150.2 (d, 2JPC = 9 Hz, Cipso), 166.6 (d, 3JPC = 4 Hz, NCH-C = O), 169.7
(d, JPC = 7 Hz, P-CH-C = O), 170.4 (N-C=O). 31P NMR (202.4 MHz,
2
CDCl3) δ : 12.67 (C-P( = O)(OPh)2.
(2R, 3R) or (2S, 3S)-Dimethyl
2-Acetamido-3-(diphenoxyphosphoryl)succinate (7)
IR (KBr) (νmax, cm−1) 3359 (NH), 1739 (C=O), 1668 (C=C), 1280
1
(P=O). H NMR (500.1 MHz, CDCl3) δ 1.97 (3H, s, O = C-CH3), 3.68

3036
N. Zabarjad-Shiraz et al.
and 3.76 (6 H, 2 s, 2 OCH3), 4.34 (1 H, dd, 2JPH = 24.0 Hz, 3JHH = 3.5
Hz, CH-P), 5.62 (1 H, ddd, 3JPH = 9.0 Hz, 3JHH = 3.5 Hz, 3JNH = 9 Hz,
3
N-CH), 6.80 (1 H, d, JHH = 9 Hz, NH), 7.1–7.3 (10 H, m, 2 OPh). 13C
1
NMR (125.8 MHz, CDCl3) δ 23.1 (O = C-CH3) 47.9 (d, JPC = 138 Hz,
2
P-C), 49.0 (d, JPC = 3.9 Hz, N-CH), 53.6 and 53.9 (2 OCH3), 120.8 (d,
3
3JPC = 4 Hz, Cortho) 120.9 (d, JPC = 4 Hz, Cortho), 126.2 and 126.3 (2
Cpara), 130.3 and 130.4 (2 Cmeta), 149.8 (d, 2JPC = 9 Hz, Cipso), 150.3 (d,
2JPC = 9 Hz, Cipso), 166.8 (d, 3JPC = 22 Hz, NCH-C = O), 168.3 (PCH-C
= O), 171.7 (N-C=O). 31P NMR (202.4 MHz, CDCl3) δ 11.98 (C-P( =
O)(OPh)2.
Triphenyl Acetylphosphorimidate (8)
White powder. IR (KBr) (νmax, cm−1) 1590 (P=N), 1666 (C=C).
MS (EI, 70 eV): m/z (%) = 367 (M+, 8), 310 (100). Anal Calcd for
C20H18NO4P (367.4): C, 65.39; H. 4.94; N, 3.81. Found: C, 65.3; H.
1
5.1; N, 3.7. H NMR (500.1 MHz, CDCl3) δ: 2.21 (3 H, s, O = C-CH3),
7.1–7.6 (15 H, m, 3 OPh) 13C NMR (125.8 MHz, CDCl3) δ 23.3 (CH3),
2
120.6 (d, 3JPC = 5 Hz, Cortho), 125.4 (Cpara) 129.9 (Cmeta) 151.3 (d, JPC
= 7 Hz, Cipso), 176.2 (C=O). 31P NMR (202.4 MHz, CDCl3) δ: -11.29
((PhO)3P=N).
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3037
[13] M. Karplus, J. Am. Chem. Soc., 88, 2870 (1963).
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