Microwave-assisted phospha-Michael addition of dialkyl phosphites, a phenyl-H-phosphinate, and diphenylphosphine oxide to maleic derivatives

Article abstract of DOI:10.1002/hc.21007

A series of new >P(O)-substituted succinic derivatives was synthesized by the microwave-assisted phospha-Michael addition of dialkyl phosphites, ethyl phenyl-H-phosphinate, and diphenylphosphine oxide to N-phenyl and N-methyl maleimide, as well as to maleic acid anhydride.

Full text of DOI:10.1002/hc.21007

Heteroatom Chemistry
Volume 23, Number 3, 2012
Microwave-Assisted Phospha-Michael
Addition of Dialkyl Phosphites,
a Phenyl-H-Phosphinate, and
Diphenylphosphine Oxide to Maleic Derivatives
Erika Ba´lint,1 Judit Taka´cs,1 La´szlo´ Drahos,2 and Gyo¨rgy Keglevich1
1Department of Organic Chemistry and Technology, Budapest University of Technology and
Economics, 1521 Budapest, Hungary
2Hungarian Academy of Sciences, Chemical Research Center, 1525 Budapest, Hungary
Received 1 December 2011; revised 11 January 2012
to afford γ -ketophosphonates, γ -ketophosphinates,
ABSTRACT: A series of new >P(O)-substituted
or γ -ketophosphine oxides. Asymmetric phospha-
succinic derivatives was synthesized by the
microwave-assisted phospha-Michael addition of
dialkyl phosphites, ethyl phenyl-H-phosphinate, and
Michael variations using chiral P-reagents are also
well known [7–9]. The addition of >P(O)H species to
α,β-unsaturated C O or P O compounds may lead
to derivatives that are of potential biological activity
diphenylphosphine oxide to N-phenyl and N-methyl
ꢀ
C
maleimide, as well as to maleic acid anhydride. 2012
[10,11].
Wiley Periodicals, Inc. Heteroatom Chem 23:235–240,
A few maleic derivative-related phospha-Michael
2012; View this article online at wileyonlinelibrary.com.
reactions are known from the literature. The adduct
DOI 10.1002/hc.21007
formed from the interaction of N-phenylmaleimide
and diphenylphosphine oxide was isolated in 73%
after boiling the components in toluene for 8 h [12].
Applying 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD)
as the catalyst and toluene as the solvent, the addi-
tion was already completed after 5 min at 26◦C [13].
Besides diphenylphosphine oxide, diphenyl phos-
phite was also used as the reagent [13]. The η1 − N-
maleimidato ligand has also been shown to undergo
the phospha-Michael reaction with >P(O)H species
in the coordination sphere [14]. N-Arylmaleimides
were reacted with bis(pentafluorophenyl)phosphine
oxide in chloroform at the boiling point [15]. It is
noteworthy that the addition of silylphosphines to
N-phenylmaleimide followed by oxidation with 30%
hydrogen peroxide also led to maleimide- >P(O)H
adduct-type products [16].
INTRODUCTION
The phospha-Michael addition is an important P C
bond-forming reaction in synthetic organic chem-
istry. The nucleophiles may include tervalent P-
reagents, such as phosphines, phosphinites, and
phosphonites, or more often >P(O)H species, such
as dialkyl phosphites, secondary phosphine oxides,
and other related derivatives [1–6]. The addition of
>P(O)H species to α,β-unsaturated ketones and es-
ters is usually carried out under basic conditions
Correspondence to: Gyo¨rgy Keglevich; e-mail: gkeglevich@
mail.bme.hu.
Contract grant sponsor: Hungarian Scientific and Research
Fund.
One author of this article investigated the ad-
dition of >P(O)H species under different condi-
tions to simple model compounds [17,18]. Later
Contract grant sponsor: OTKA K83118.
2012 Wiley Periodicals, Inc.
c
ꢀ
235

236 Ba´lint et al.
O
on, >P(O)H species were added on the double
bond of 1-phenyl-2-phospholene 1-oxide and 1-
substituted-1,2-dihydrophosphinine oxides to afford
a 3-(>P(O)-)phospholane oxide [19] and 3-(>P(O)-)
1,2,3,6-tetrahydrophosphinine oxides, respectively
[20–22]. The bis(phosphinoxido) derivatives served
as bidentate P-ligands after double deoxygena-
tion and led to cis chelate ring Pt complexes
on reaction with dichlorodibenzonitrile platinum
[19,23]. Because of the unreactivity of the sub-
strates, microwave (MW) irradiation was not useful
in the phospha-Michael reaction of 2-phospholene
1-oxides and 1,2-dihydrophosphinine 1-oxides.
In this paper, we investigate the phospha-
Michael additions of >P(O)H species to maleic
derivatives in which MW irradiation may promote
the reaction.
O
O
MW
175°C, 2.5−3 h
(RO)2P
2
3
4
N Y
(RO)2P(O)H
N Y
+
5
No solvent
O
O
Y
Ph
Me
1
2
R = Et (a), Me (b)
SCHEME 1
O
O
O
P
MW
175°C, 2.5 h
EtO
Ph
2
3
4
N Y
+
Ph(EtO)P(O)H
N Y
5
No solvent
O
O
Y
Ph
Me
3
4
SCHEME 2
RESULTS AND DISCUSSION
In the first experiments, dialkyl phosphites, such
as diethyl phosphite and dimethyl phosphite, were
reacted with N-phenyl- and N-methylmaleimides
(NPMI and NMMI) under solventless conditions
and MW irradiation. Completion of the additions
at 150◦C required a reaction time of 6–7 h. Apply-
ing a reaction temperature of 175◦C, the addition
of dialkyl phosphites to NPMI was complete after
2.5 h, whereas with NMMI the reaction time was 3 h.
This experience is the consequence of the somewhat
more enhanced reactivity of NPMI as compared
to NMMI. The 3-(>P(O)-)-substituted succinimide
derivatives (1a, 1b, 2a, and 2b) were obtained in 71–
95% yields after column chromatography (Table 1,
entries 1–4; Scheme 1).
O
O
O
MW
120°C, 3 h
Ph2P
25 N Y
O
3
4
N Y
Ph2P(O)H
+
Acetonitrile
O
Y
Ph
Me
5
6
SCHEME 3
cause of the P-chiral center in the reagent and
the prochiral center in the substrate, the Michael
adducts (3 and 4) were formed as a ∼51:49 mixture
of two diastereomers. The yields of products 3 and4
were 92% and 80%, respectively (Table 1, entries 5
and 6).
Diphenylphosphine oxide could already be
added on the double bond of maleimides at 120◦C/3 h
on MW irradiation. The 3-Ph2P(O)-succinimides
5 and 6 were obtained in 97% and 98% yields,
(Table 1, entries 7 and 8; Scheme 3).
The succinimides (1a, 1b, 2a, 2b, 3, 4, and 6)
were characterized by 31P, 13C, and 1H NMR, as well
as mass spectral methods. Adducts 1a and 5 are
known from the literature [24,12,13], but for com-
pound 1a no characterization has been provided.
For this, compound 1a was also characterized
fully by us. As a consequence of the stereogenic C3
center, diastereotopy of the P-substituents could
be observed in the 13C and 1H NMR spectra of
compounds 1a, 1b, 2a, and 2b and in the13C NMR
spectrum of product 6.
The addition of ethyl phenyl-H-phosphinate to
maleimide derivatives was carried out under sim-
ilar conditions (MW, 175◦C, 0.5-3 h) to afford 3-
P(O)PhEtO-succinimides 3 and 4 (Scheme 2). Be-
TABLE 1 Phospha-Michael Reactions with Maleic Deriva-
tives under MW Conditions
Starting Materials
T (◦C) t (h) Yield (%) Entry
NPMI + (EtO)2P(O)H
NPMI + (MeO)2P(O)H
NMMI + (EtO)2P(O)H
NMMI + (MeO)2P(O)H
NPMI + (EtO)PhP(O)H
NMMI + (EtO)PhP(O)H
NPMI + Ph2P(O)H
175
175
175
175
175
175
120
120
120
120
2.5
2.5
3
3
2.5
3
3
3
3
3
83 (1a)
81 (1b)
95 (2a)
71 (2b)
92 (3)a
80 (4)a
97 (5)
1
2
3
4
5
6
7
8
9
NMMI + Ph2P(O)H
98 (6)
MAA + (EtO)2P(O)H
49 (7)
66 (8)
MAA + Ph2P(O)H
10
Comparative thermal experiments were also car-
ried out (Table 2). Regarding the addition of diethyl
aAs a ca 1:1 mixture of two isomers.
Heteroatom Chemistry DOI 10.1002/hc

Novel >P(O)-Substituted Succinic Derivatives Synthesized by Microwave-Assisted Phospha-Michael Addition 237
TABLE 2 Phospha-Michael Reactions with Maleimide Derivatives under Thermal Conditions
Starting Materials
Solvent
T (◦C)
t (h)
Conversion (%)
Yield (%)
Entry
NPMI + (EtO)2P(O)H
NPMI + (EtO)2P(O)H
NPMI + (EtO)2P(O)H
NMMI + (EtO)2P(O)H
NPMI + Ph2P(O)H
PhMe
o-xylene
–
110
144
175
175
110
24
12
3.5
4
0
1
2
3
4
5
32 (1a)
84 (1a)a
69 (2a)a
100 (5)
72
–
PhMe
8
93 (73 [12])
aNo improvement on further heating.
phosphite to NPMI, there was no reaction at all in
boiling toluene after a 24-h reaction time (Table 2,
entry 1). Carrying out the reaction in o-xylene at the
boiling point (144◦C) for 12 h, the conversion was
32% (Table 2, entry 2). Applying a reaction tempera-
ture of 175◦C for 3.5 h in the absence of any solvent,
the conversion was 84% that did not increase on
additional heating. In this case, product 1a was iso-
lated in 72% (Table 2, entry 3). The similar reaction
of NMMI with diethyl phosphite led to a conversion
of 69% after 4 h (Table 2, entry 4). Finally, the addi-
tion of diphenylphosphine oxide to NPMI had to be
carried out in toluene as the solvent and it was found
that at 110◦C the reaction took place in a quantita-
tive conversion after 8 h (Table 2, entry 5). It can
be seen that the thermal phospha-Michael additions
were slower than the MW variations; moreover, ex-
cept in one case, the final conversions were not quan-
titative.
In summary, a series of >P(O)-substituted
maleic derivatives was synthesized by the MW-
assisted and, in most cases, solvent-free phospha-
Michael addition of dialkyl phosphites, ethyl phenyl-
H-phosphinate, or diphenylphosphine oxide to
N-substituted maleimides or maleic anhydride, in
most instances with competent (on average 81%)
yields and in a short (2.5–3 h) reaction time. The
thermal phospha-Michael additions were slower
and, in almost all cases, the final conversions were
not quantitative. The advantage of the MW-assisted
method developed is that there is no need for a sol-
vent and catalyst. At the same time, a temperature
of 120–175◦C has to be applied. A literature method
describes analogous reactions at room temperature
in the presence of TBD as the catalyst in a toluene
solution in quite a short reaction time [13]. The ad-
vantage of this method is that the reactions may be
carried out at room temperature; the disadvantage
is that there is a need for a solvent and a catalyst.
Phospha-Michael additions to maleic acid an-
hydride (MAA) were also investigated under MW
irradiation. The addition of diethyl phosphite and
diphenylphosphine oxide to MAA could be best ac-
complished at 120◦C and 175◦C, respectively, to fur-
nish the corresponding adducts (7 and 8) after a re-
action time of 3 h (Scheme 4). In these cases, the
yield of products 7 and 8 was 49% and 66%, respec-
tively (Table 1, entries 9 and 10). The adducts (7 and
EXPERIMENTAL
General
1
The 13C and H NMR spectra were obtained in a
CDCl3 solution on a Bruker DRX-500 spectrometer
operating at 125.7 and 500.1 MHz, respectively. The
1
13C and H chemical shifts are referred to as TMS.
1
8) were characterized by 31P, 13C, and H NMR, as
31P NMR spectra were obtained on a Bruker AV-300
spectrometer. Chemical shifts are downfield relative
to 85% H3PO4. Mass spectrometry was performed on
a ZAB-2SEQ instrument. The reactions were carried
out in a 300-W CEM Discover focused microwave
reactor equipped with a pressure controller applying
30–50 W under isothermal conditions.
well as the mass spectral data. Duplication of the
ethoxy and a part of the phenyl carbon atom sig-
nals in the 13C NMR spectra of compounds 7 and
8, respectively, referred to the phenomenon of di-
astereotopy.
O
O
O
MW
120-175°C, 3 h
Z2P
25 O
O
3
4
O
Z2P(O)H
+
General Procedure for the Preparation of
2-(Dialkoxyphosphonyl)succinimide Derivatives
1 and 2
No solvent (Z = EtO)
Acetonitrile (Z = Ph)
O
Z
EtO
Ph
7
8
A mixture of 2.0 mmol of maleimide (0.35 g of N-
phenylmaleimide or 0.22 g of N-methylmaleimide)
and 2.0 mmol of the >P(O)H species (0.28 mL of
SCHEME 4
Heteroatom Chemistry DOI 10.1002/hc

238 Ba´lint et al.
diethyl phosphite or 0.18 mL of dimethyl phosphite)
was heated at 175◦C in a vial in the MW reactor
for 2.5 h (NPMI) and for 3 h (NMMI). The water
formed was removed in vacuo. Column chromatog-
raphy (silica gel 3% methanol in dichloromethane)
of the residue afforded the products (1a, 1b, 2a, and
2b) as oils.
3H, OCH3); [M + H]+found = 222.0531, C7H13NO5P
requires 222.0531.
3-(Ethyl phenylphosphinyl)succinimide
Derivatives 3 and 4
These compounds were prepared similarly using the
same amount of maleimide with 2.0 mmol (0.30 mL)
of ethyl phenylphosphonate. The products were ob-
tained as oils.
The following products were thus prepared:
2-(Diethoxyphosphonyl)-N-phenylsuccinimide (1a)
[24]. Yield: 0.52 g (83%); 31P NMR (CDCl3) δ: 20.0;
13C NMR (CDCl3) δ: 16.45 (J = 5.8, CH3), 16.50 (J
= 5.9, CH3), 30.9 (J = 4.0, C4), 39.7 (J = 141.4, C3),
63.4 (J = 6.7, OCH2), 63.9 (J = 6.6, OCH2), 126.5
3-(Ethylphenylphosphinyl)-N-phenylsuccinimide
(3). Yield: 0.63 g (92%); 31P NMR (CDCl3) δ: 35.1
(51%) and 35.5 (49%); for the two isomers: 13C NMR
(CDCl3) δ: 16.61 and 16.70 (CH2CH3), 30.3 (J = 1.8)
and 30.5 (J = 2.8) (C4), 42.6 (J = 92.7) and 43.3
∗
∗
ꢁ
ꢁ
ꢁ
ꢁ
(C2 ) , 128.9 (C4 ), 129.3 (C3 ) , 131.8 (C1 ), 171.4 (J =
5.7, C O), 174.2 (J = 5.7, C O), ∗may be reversed; 1H
NMR (CDCl3) δ: 1.36 (t, J = 7.3, 3H, CH3), 1.41 (t, J =
7.3, 3H, CH3), 3.12–3.22 (m, 2H, C(4)H2), 3.41–3.53
(m, 1H, C(3)H), 4.20–4.34 (m, 4H, OCH2), 7.27–7.51
(m, 5H, Ar); [M + H]+found = 312.1006, C14H19NO5P
requires 312.1001.
(J = 92.5) (C3), 62.56 (J = 5.7) and 62.64 (J = 6.2)
a
ꢁ
ꢁ
(OCH2), 126.5 and 126.7 (C3 ) , 129.0 (C4 ), 129.05
b
ꢁꢁ
(J = 11.5) and 129.11 (J = 9.9) (C3 ) , 129.3 and
a
ꢁ
ꢁ
129.4 (C2 ) , 131.7 and 131.9 (C1 ), 132.7 (J = 10.2)
b
ꢁꢁ
ꢁꢁ
(C2 ) , 133.6 (J = 2.9) and 133.7 (J = 2.8) (C4 ),
171.7 (J = 2.6) and 171.9 (J = 5.5) (C O), 173.9
(J = 4.6) and 174.2 (J = 4.2) (C O) a,bmay be
2-(Dimethoxyphosphonyl)-N-phenylsuccinimide
(1b). Yield: 0.46 g (81%); 31P NMR (CDCl3) δ: 22.7;
13C NMR (CDCl3) δ: 30.8 (J = 3.9, C4), 39.4 (J =
143.0, C3), 53.6 (J = 6.8, OCH3), 54.5 (J = 6.6,
ꢁ
ꢁ
ꢁ
ꢁ
reversed, C1 , C2 , C3 , and C4 refer to the correspond-
ing carbon atoms of the N-phenyl ring, whereas
ꢁꢁ
ꢁꢁ
ꢁꢁ
C2 , C3 , and C4 refer to the respective carbon
atoms of the P-phenyl ring; 1H NMR (CDCl3) δ: 1.36
(t, J = 7.1) (CH2CH ), 1.42 (t, J = 7.1) (CH2CH ) total
∗
∗
ꢁ
ꢁ
ꢁ
OCH3), 126.6 (C2 ) , 129.1 (C4 ), 129.4 (C3 ) , 131.7
ꢁ
(C1 ), 171.3 (J = 5.4, C O), 174.0 (J = 6.2, C O),
∗may be reversed; 1H NMR (CDCl3) δ: 3.10–3.27
(m, 2H, C(4)H2), 3.43–3.56 (m, 1H, C(3)H), 3.87
(J = 10.0, 3H, OCH3), 3.91 (J = 10.8, 3H, OCH3),
7.27–7.51 (m, 5H, Ar); [M + H]+found = 284.0681,
C12H15NO5P requires 284.0688.
3
3
intensity 3H, 2.98–3.37 (m, 2H, C(4)H2), 3.50–3.73
(m, 1H, C(3)H), 4.00–4.34 (m, 2H, OCH2), 6.98–7.94
(m, 10H, Ar); [M + H]+found = 344.1045, C18H19NO4P
requires 344.1052.
2- ( Diethoxyphosphonyl)-N-methylsuccinimide
(2a). Yield: 0.47 g (95%); 31P NMR (CDCl3) δ: 20.1;
13C NMR (CDCl3) δ: 16.58 (J = 5.9, CH2CH3), 16.62
(J = 5.8, CH2CH3), 25.6 (NCH3), 30.9 (J = 3.8, C4),
39.7 (J = 143.2, C3), 63.3 (J = 6.7, OCH2), 63.7
(J = 6.6, OCH2), 172.4 (J = 5.1, C O, 175.2 (J =
3-(Ethylphenylphosphinyl)-N-methylsuccinimide
(4). Yield: 0.45 g (80%); 31P NMR (CDCl3) δ: 35.60
(51%) and 35.63 (49%); for the two isomers: 13C
NMR (CDCl3) δ: 16.46 and 16.53 (CH2CH3), 25.2
and 25.4 (N-CH3), 29.9 (J = 2.2) and 30.2 (J =
2.2) (C4), 42.4 (J = 94.9) and 42.8 (J = 94.3) (C3),
1
6.2, C O); H NMR (CDCl3) δ: 1.36 (t, J = 7.0, 3H,
62.2 (J = 6.2) and 62.5 (J = 6.4) (OCH2), 128.92
∗
CH2CH ), 1.38 (t, J = 7.0, 3H, CH2CH ), 2.97–3.05
3
3
ꢁꢁ
(J = 13.4) and 128.94 (J = 13.2) (C3 ) , 132.37 (J =
∗
(m, 2H, C(4)H2), 3.03 (s, 3H, NCH3), 3.25–3.38 (m,
1H, C(3)H), 4.17–4.28 (m, 4H, OCH2); [M + H]f+ound
= 250.0843, C9H17NO5P requires 250.0844.
ꢁꢁ
10.2) and 132.41 (J = 10.0) (C2 ) , 133.4 (J = 2.8)
ꢁꢁ
and 133.5 (J = 2.9) (C4 ), 172.5 (broad, d, J = 5.3)
(C O), 174.9 (J = 4.9) and 175.0 (J = 5.0) (C O)
∗
ꢁꢁ
ꢁꢁ
ꢁꢁ
tentative assignment, C2 , C3 , and C4 refer to the
2-(Dimethoxyphosphonyl)-N-methylsuccinimide
(2b). Yield: 0.31 g (71%); 31P NMR (CDCl3) δ: 20.7;
13C NMR (CDCl3) δ: 25.4 (NCH3), 30.4 (J = 3.8, C4),
38.8 (J = 144.7, C3), 53.4 (J = 6.8, OCH3), 54.2
(J = 6.6, OCH3), 171.9 (J = 5.1, C O), 174.8
corresponding carbon atoms of the P-phenyl ring;
1H NMR (CDCl3) δ: 1.33 (t, J = 7.1) (CH2CH ), 1.39
3
(t, J = 7.0) (CH2CH ) total intensity 3H, 2.72–3.15
3
(m, C(4)H2), 2.85 (s, NCH3), and 3.00 (s, NCH3)
overlapped, total intensity 5H, 3.35–3.55 (m, 1H,
C(3)H), 3.99–4.30 (m, 2H, OCH2), 7.49–7.90 (m, 5H,
Ar); [M + H]+found = 282.0898, C13H17NO4P requires
282.0895.
1
(J = 6.7, C O); H NMR (CDCl3) δ: 2.94–2.98 (m,
2H, C(4)H2), 3.01 (s, 3H, NCH3), 3.29–3.42 (m, 1H,
C(3)H), 3.84 (J = 11.0, 3H, OCH3), 3.87 (J = 10.9,
Heteroatom Chemistry DOI 10.1002/hc

Novel >P(O)-Substituted Succinic Derivatives Synthesized by Microwave-Assisted Phospha-Michael Addition 239
the MW reactor for 3 h. The workup was similar as
mentioned above. Yield: 1.2 g (66%) of compound
8 as a dense oil. 31P NMR (CDCl3) δ: 34.6; 13C NMR
(CDCl3) δ: 31.1 (C4), 44.4 (J = 59.8, C3), 128.9 (J =
3-(Diphenylphosphinoyl)succinimide
Derivatives 5 and 6
A mixture of 2.0 mmol of maleimide (0.35 g of N-
phenylmaleimide or 0.22 g of N-methylmaleimide)
and 2.0 mmol (0.40 g) of diphenylphosphine oxide in
3 mL of acetonitrile was heated at 120◦C in a vial in
the MW reactor for 3 h. The workup was similar as
mentioned above. Yield: 0.75 g (97%) of compound
5 and 0.61 g (98%) of compound 6, both as white
crystals.
∗
∗
12.0, C∗3 and C ), 130.8 (J = 9.7, C ) , 130.9 (J =
ꢁ
ꢁ
ꢁ
ꢁꢁ
2
3
∗
ꢁꢁ
ꢁꢁ
88.3, C1 and C1 ), 131.3 (J = 9.7, C2 ) , 132.3 (J =
ꢁ
ꢁꢁ
2.8, C4 ), 132.5 (J = 2.9, C4 ), 168.2 (J = 2.9, C O),
∗
171.1 (J = 14.7, C O), tentative assignments re-
garding the C2 and C3 carbon atoms of the phenyl
1
rings; H NMR (CDCl3) δ: 2.78–2.90 and 3.22–3.32
(m, 2H, C(4)H2), 3.99–4.17 (m, 1H, C(3)H), 7.45–7.90
(m, 10H, Ar); [M + H]+found = 301.0610, C16H14O4P re-
quires 301.0630.
3-(Diphenylphosphinoyl)-N-phenylsuccinimide
(5). mp: 132–134◦C, mp [12,14]: 134–136◦C; +31P
NMR (CDCl3) δ: 30.4, δP [25,14]: 31.2; [M + H]found
= 376.0934, C22H19NO3P requires 376.0922.
ACKNOWLEDGMENTS
This work is connected to the scientific program
of the “Development of quality-oriented and har-
monized R+D+I strategy and functional model at
BME” project. This project is supported by the
New Sze´chenyi Plan (Project ID: TAMOP-4.2.1/B-
09/1/KMR-2010-0002).
3-(Diphenylphosphinoyl)-N-methylsuccinimide
(6). mp: 164◦C; 31P NMR (CDCl3) δ: 30.4; 13C NMR
(CDCl3) δ: 25.3 (CH3), 30.1 (J = 2.0, C4), 42.6 (J =
a
ꢁ
63.1, C3), 128.9 (J = 12.4, C3 ) , 129.2 (J = 12.4,
´
a
b
b
ꢁꢁ
ꢁ
ꢁꢁ
C3 ) , 130.8 (J = 108.7, C1 ) , 130.9 (J= 107.3, C1 ) ,
a
a
ꢁ
ꢁꢁ
131.6 (J = 20.4, C2 ) , 131.7 (J = 20.2, C2 ) , 132.9
c
c
ꢁ
ꢁꢁ
(J = 2.7, C4 ) , 132.9 (J = 2.7, C4 ) , 173.0 (J = 3.6,
a
C O), 174.9 (J = 4.3, C O), tentative assignment,
b,cmay be reversed; 1H NMR (CDCl3) δ: 2.83 (s,
REFERENCES
CH3), 2.88–3.22 (m, 2H, C(4)H2), 3.91–4.00 (m, 1H,
[1] Enders, D.; Saint-Dizier, A.; Lannou, M.-I.; Lenzen,
A. Eur J Org Chem 2006, 29–49.
[2] Tanaka, M. J. Top Curr Chem 2004, 232, 25–54.
[3] Alonso, F.; Beletskaya, I. P.; Yus, M. Chem Rev 2004,
104, 3079–3159.
C(3)H), 7.47–7.96 (m, 10H, ArH); [M + H]f+ound
=
314.0946, C17H17NO3P requires 314.0946.
[4] Pudovik, A. N.; Konovalova, I. V. Synthesis 1979, 81–
96.
2-(Diethoxyphosphonyl)succinanhydride (7)
[5] Enders, D.; Tedeschi, L.; Bats, J. W. Angew Chem, Int
Ed 2000, 39, 4605–4607.
[6] Stockland, R. A.; Taylor, R. I.; Thompson, L. E.; Patel,
P. B. Org Lett 2005, 7, 851–853.
[7] Tedeschi, L.; Enders, D. Org Lett 2001, 3, 3515–
3517.
[8] Enders, D.; Tedeschi, L.; Bats, J. W. Angew Chem
2000, 112, 4774–4776.
[9] Enders, D.; Tedeschi, L.; Bats, J. W. Angew Chem, Int
Ed 2000, 39, 4605–4607.
[10] Jackson, P. F.; Slusher, B. S. Curr Med Chem 2001,
8, 949–957.
[11] Harsa´nyi, K.; Doma´ny, Gy.; Greiner, I.; Forintos,
H.; Keglevich, G. Heteroatom Chem 2005, 16, 562–
565.
[12] Van Es, J. J. G. S.; Jaarsveld, K.; Gen, A. J Org Chem
1990, 55, 4063–4069.
A mixture of 6.0 mmol (0.60 g) of maleic anhy-
dride and 6.0 mmol (0.78 mL) of diethyl phosphite
was heated at 120◦C in a vial in the MW reactor
for 3 h. The water formed was removed in vacuo.
Column chromatography (silica gel, 3% methanol
in dichloromethane) of the residue afforded 0.69 g
(49%) of adduct 7 as an oil. 31P NMR (CDCl3) δ: 21.8;
13C NMR (CDCl3) δ: 16.56 (J = 6.1, CH3), 16.59 (J
= 6.0, CH3), 31.6 (J = 4.4, C4), 41.4 (J = 131.1, C3),
64.2 (J = 2.7, OCH2), 64.3 (J = 2.9, OCH2), 171.5
(J = 5.0, C O), 175.4 (J = 19.2, C O); 1H NMR
(CDCl3) δ: 1.33 (t, J = 7.0, 3H, CH3), 1.34 (t, J = 7.0,
3H, CH3), 2.76–3.12 (m, 2H, C(4)H2), 3.45–3.58 (m,
1H, C(3)H), 4.13–4.23 (m, 4H, OCH2); [M + H]f+ound
= 237.0533, C8H14O6P requires 237.0528.
[13] Jiang, Z.; Zhang, Y.; Ye, W.; Tan, C.-H. Tetrahedron
Lett 2007, 48, 51–54.
[14] Rudolf, B.; Salmai, M.; Palusiak, M.; Zakrzewski, J. J
Organomet Chem 2009, 694, 908–915.
[15] Frolova, N. G.; Savin, E. D.; Goryunov, E. I.; Lysenko,
K. A.; Nelyubina, Yu. V.; Petrovskii, P. V.; Nifant’ev,
E. E. Dokl Chem 2010, 430, 18–23.
[16] Trepohl, V. T.; Mori, S.; Itami, K.; Oestreich, M. Org
Lett 2009, 11, 1091–1094.
3-(Diphenylphosphinoyl)succinanhydride (8)
A mixture of 6.0 mmol (0.60 g) of maleic anhydride
and 6.0 mmol (1.2 g) of diphenylphosphine oxide in
3 mL of acetonitrile was heated at 120◦C in a vial in
Heteroatom Chemistry DOI 10.1002/hc

240 Ba´lint et al.
[17] Keglevich, G.; Sipos, M.; Taka´cs, D.; Greiner, I. Het-
eroatom Chem 2007, 18, 226–229.
[18] Keglevich, G.; Sipos, M.; Taka´cs, D.; Luda´nyi, K. Het-
eroatom Chem 2008, 19, 288–292.
[19] Pietrusiewicz, K. M.; Flis, A.; Ujj, V.; Ko¨rtve´lyesi, T.;
Drahos, L.; Pongra´cz, P.; Kolla´r, L.; Keglevich, G.
Heteroatom 2011, 22, 730–736.
[20] Keglevich, G.; Sipos, M.; Imre, T.; Luda´nyi, K.;
Szieberth, D.; To´´ke, L. Tetrahedron Lett 2002, 43,
8515–8518.
[21] Keglevich, G.; Sipos, M.; Szieberth, D.; Nyula´szi, L.;
Imre, T.; Luda´nyi, K.; To´´ke, L. Tetrahedron 2004, 60,
6619–6627.
[22] Sipos, M.; Ko¨rtve´lyesi, T.; Ujj, V.; Luda´nyi, K.; Ve´key,
K.; To´´ke, L.; Keglevich, G. Heteroatom Chem 2007,
18, 747–753.
[23] Keglevich, G.; Sipos, M.; Szieberth, D.; Peto¨cz, G.;
Kolla´r, L. J Organomet Chem 2004, 689, 3158–3162.
[24] Pudovik, A. N.; Batyeva, E. S.; Grifanova, Y. N. J Gen
Chem USSR 1973, 43, 1681–1683.
Heteroatom Chemistry DOI 10.1002/hc