A salt-free synthesis of 1,2-bisphosphorylethanes via an efficient PMe3-catalyzed addition of >P(O)H to vinylphosphoryl compounds

Article abstract of DOI:10.1016/j.tetlet.2015.07.077

Abstract A convenient and versatile method was developed for the preparation of 1,2-bisphosphorylethanes. Thus, in the presence of a catalytic amount of trimethylphosphine, a variety of >P(O)H compounds efficiently add to vinylphosphoryl compounds to produce the corresponding 1,2-bisphosphorylethanes in high yields. In most cases, the trimethylphosphine catalyst was simply removed under vacuum leaving spectroscopically pure adducts. The present method provided a halogen and metal-free clean process for the preparation of 1,2-bisphosphorylethanes.

Full text of DOI:10.1016/j.tetlet.2015.07.077

Tetrahedron Letters 56 (2015) 5303–5305
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Tetrahedron Letters
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A salt-free synthesis of 1,2-bisphosphorylethanes via an efficient
PMe3-catalyzed addition of >P(O)H to vinylphosphoryl compounds
Yuta Saga a,b, Daoqing Han c, Shin-ichi Kawaguchi a, Akiya Ogawa a, Li-Biao Han c,
⇑
a Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan
b Katayama Chemical Industries Co., Ltd, 26-22, 3-Chome, Higasinaniwa-cho, Amagasaki, Hyogo 660-0892, Japan
c National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1, Higashi, Tsukuba, Ibaraki 305-8565, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient and versatile method was developed for the preparation of 1,2-bisphosphorylethanes. Thus,
in the presence of a catalytic amount of trimethylphosphine, a variety of >P(O)H compounds efficiently
add to vinylphosphoryl compounds to produce the corresponding 1,2-bisphosphorylethanes in high
yields. In most cases, the trimethylphosphine catalyst was simply removed under vacuum leaving spec-
troscopically pure adducts. The present method provided a halogen and metal-free clean process for the
preparation of 1,2-bisphosphorylethanes.
Received 2 June 2015
Revised 17 July 2015
Accepted 29 July 2015
Available online 4 August 2015
Keywords:
Ó 2015 Published by Elsevier Ltd.
Organohosphorus compound
Hydrophosphorylation
Vinylphosphorus compound
Phosphine catalyst
Introduction
double-hydrophosphorylation of alkynes,10 were also known.
However, the scope of these reactions is limited and the use of a
In recent years, phosphorus compounds are widely used as
halogen-free flame retardants. These phosphorus compounds are
added to organic polymers to improve their fire retardancy.1 It is
generally known that, for a phosphorus compound, the higher con-
tent of the phosphorus, results in the better performance of the
retardancy.2 We are currently studying new phosphorus-based fire
retardants for electronic materials such as sealant, printed wiring
large amount of the metal catalyst also complicated the
purification of the products.
In addition to the above mentioned utility as fire retantants,
1,2-bisphosphorylethanes 1 are also important compounds in catal-
ysis and biochemistry. For example, 1,2-bisphosphorylethanes 1 are
convenient
precursors
for
the
preparation
of
1,2-bisphosphinoethanes ligands which are important for transition
metal catalysts.11 Furthermore, compounds 1 can ligate metals and
serve as excellent metal extractants.12 More importantly, analogues
of 1 are used as drugs treating bone and dental diseases.13
Herein we disclose an efficient halogen and metal-free method
for the preparation of compound 1: in the presence of a catalytic
amount of trimethylphosphine, a variety of >P(O)H compounds 2
efficiently add to the commercially available vinylphosphoryl com-
pounds 3 to produce the corresponding 1,2-bisphosphorylethanes
1 in high yields (Scheme 1). The highly catalytic efficiency of
board and are interested in 1,2-bisphosphorylethane
1
(>P(O)CH2CH2P(O)<) because of its high phosphorus content.3
However, despite a few methods for the preparation of 1 are
reported, none of them is suitable for the preparation of the fire
retardant used for electronic materials (Scheme 1), because of
the heavy use of halogen compounds and metals which, as
impurities, can damage the electronic devices made from these
phosphorus fire-retardant-containing materials.4 For example,
1,2-bisphosphoryl ethane 1 was prepared using the Arbusov reac-
tions via the reaction of 1,2-dihaloethanes and phosphites.5–7 The
reaction of Z1Z2P(O)Cl with XMgCH2CH2MgX could also produce
compound 1. Compound 1 was also obtained via reactions of
1,2-bis(dichlorophosphoryl)ethane with an organometallic reagent
or alcohol.8 Other methods such as a radical or base catalyzed
R2POR
ClCH2CH2Cl
P(O)Z1Z2
Z1Z2P(O)H
cat PMe3
2
XMgCH2CH2MgX
RMgX/RLi/ROH
+
Z1Z2P(O)Cl
Cl2(O)PCH2
P(O)Z3Z4
P(O)Z3Z4
3
addition of P(O)-H compounds,9 and
a
nickel-catalyzed
2
1
Traditional method:
heavy use of halo- and metal compounds
This work: halogen and metal-free
⇑
Corresponding author. Tel.: +81 29 861 4855; fax: +81 29 861 6344.
E-mail address: libiao-han@aist.go.jp (L.-B. Han).
Scheme 1. New efficient and clean preparation of 1.
http://dx.doi.org/10.1016/j.tetlet.2015.07.077
0040-4039/Ó 2015 Published by Elsevier Ltd.

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Y. Saga et al. / Tetrahedron Letters 56 (2015) 5303–5305
Me3P and its easy removal from the products14 greatly facilitate
the preparation of 1. For example, an NMR spectroscopically pure
1 can be obtained quantitatively by simply mixing 2 and 3 at room
temperature in the presence of a catalytic amount of PMe3 which,
after the reaction, can completely remove from the products under
vacuum.15
Table 2
Solvent effects on PMe3-catalyzed addition of dimethyl phosphite to dimethyl
vinylphosphonate affording 1aa
(MeO)2P(O)
+
(MeO)2P(O)H
P(O)(OMe)2
P(O)(OMe)2
1a
Entry
Solvent
Time (h)
GC yield (%)
Results and discussion
1
2
3
4
5
THF
4
20
4
20
4
20
4
20
4
94
Quantitative
94
Quantitative
93
Quantitative
90
95
24
Toluene
AcOEt
CH2Cl2
MeOH
A
mixture of dimethyl phosphite (1 mmol) and dimethyl
vinylphosphonate (1 mmol) in THF (1 mL) was stirred at room
temperature. The reaction was followed by GC (Table 1). No addi-
tion product 1a could be detected in the absence of a catalyst after
18 h (entry 1). Remarkably, however, as a catalytic amount of PMe3
(5 mol %) was added to the mixture, an exothermic reaction was
observed and the addition product 1a was formed in 74% yield
after 1 h. The adduct 1a was eventually generated quantitatively
after 18 h. As shown in Table 1, PMe3 is an exceptionally efficient
catalyst for this addition reaction. Other phosphines such as Et3P
(entry 2) and n-Bu3P (entry 3) only produced a trace amount of
1a after 1 h under similar conditions,16,17 and an aromatic phos-
phine such as Ph3P, MePh2P, and Me2PhP (entries 4–7) did not cat-
alyze the addition at all. In addition, neither trimethyl phosphite
(entry 8) nor triethylamine nor DMAP nor DABCO (entries 9–11)
could catalyze the addition either.
This PMe3-catalyzed addition could be conducted in a variety of
solvents (Table 2). Thus, in addition to THF (entry 1), the reaction
could take place in toluene (entry 2), ethyl acetate (entry 3),
dichloromethane (entry 4) to produce the corresponding bisphos-
phorylethane 1a in high yields. However, only a moderate yield
of 1a was obtained when the reaction was carried out in methanol
and no addition took place in water. Finally, and practically impor-
tantly, the reaction could take place rapidly in the absence of a sol-
vent to produce 1a quantitatively with a trace amount of PMe3
catalyst (entry 7).
20
20
4
49
0
6
7
H2O
None
Quantitative
a
Dimethyl phosphite (1.0 mmol) and dimethyl vinylphosphonate (1.0 mmol) in a
solvent (1 mL) were stirred at room temperature in the presence of PMe3 (3 mol %),
and the reaction was followed by GC.
Table 3
PMe3-catalyzed addition of various P(O)-H compounds to vinylphosphoryl
compounds
PMe3 5 mol%
Z1Z2P(O)
Z1Z2P(O)H
+
P(O)Z3Z4
THF, 20 h, rt
P(O)Z3Z4
2
1
3
Entry
2
3
Yielda (%)
O
1
2
3
4
(MeO)2P(O)H
93
71
62
59
(MeO)2P
O
(BnO)2P
By using the optimized reaction conditions, 1a could be readily
synthesized in ten-gram scales. Thus, a mixture of dimethyl phos-
phite (5.5 g, 50 mmol) and dimethyl vinylphosphonate (6.8 g,
50 mmol) in a flask was cooled with an ice water bath, and PMe3
(2.5 mL of 1.0 M PMe3 in THF, 2.5 mmol) was slowly added to
the mixture. After stirring the mixture for 0.5 h, the cooling bath
was removed and stirring continued for 20 h at room temperature.
The PMe3 catalyst was removed under vaccum (1 mmHg) to leave a
O
(PhO)2P
O
Ph(EtO)P
O
P
O
5
91
O
Ph2P
6b
7
89
69
92
O
Table 1
(i-PrO)PhP(O)H
(MeO)2P
Trimethylphosphine catalyzed addition of dimethyl phosphite to dimethyl vinylphos-
O
Ph2P
phonate affording 1aa
8
O
H
P
O
(MeO)2P(O)
+
(MeO)2P(O)H
P(O)(OMe)2
P(O)(OMe)2
(MeO)2P
O
1a
9
90
Entry
Catalyst
Time (h)
GC yield (%)
O
1
2
None
Me3P
18
1
18
1
0
74
10
11
12b
13
14
Ph2P(O)H
89
73
53
98
64
(MeO)2P
Quantitative
Trace
Trace
0
0
0
0
0
0
0
O
P
3
4
5
6
7
8
9
10
11
Et3P
n-Bu3P
Ph3P
Me2PhP
MePh2P
P(OMe)3
NEt3
DMAP
DABCO
(PhO)2
1
O
Ph2P
18
18
18
18
18
18
18
O
n-Bu2P(O)H
(MeO)2P
O
(t-Bu)PhP(O)H
(MeO)2P
a
An equimolar ratio mixture of 2 (1.0 mmol) and vinylphosphorus compound 3
a
A mixture of dimethyl phosphite (1.0 mmol) and dimethyl vinylphosphonate
(1.0 mmol) in THF (1 mL) was stirred at room temperature in the presence of PMe3
(5 mol %). Yields refer to isolated yields.
(1.0 mmol) in THF (1 mL) was stirred at room temperature in the presence of a
catalyst (5 mol %), and the reaction was followed by GC.
b
THF (2 mL), 50 °C.

Y. Saga et al. / Tetrahedron Letters 56 (2015) 5303–5305
5305
3
was substituted by the nucleophilic >P(O) moiety. Consequently,
adduct 1 was formed and PMe3 was regenerated which then initi-
ates another addition (Scheme 2).
PMe3
1
Conclusion
PMe3
Z4Z3(O)P
We have developed a halogen and metal-free process for the
preparation of bisphosphorylethanes. In the presence of a catalytic
amount of trimethylphosphine, a variety of >P(O)H compounds
efficiently add to a variety of vinylphosphoryl compounds to pro-
duce the corresponding bisphosphorylethanes in high yields. The
isolation of the adducts is simple since, after the reaction, the
trimethylphosphine catalyst used can be easily removed from the
products under vacuum leaving NMR spectroscopically pure
products.
4
H
P(O)Z 1Z2
PMe3
2
Z4Z3(O)P
5
Scheme 2. A proposed reaction mechanism for the PMe3-catalyzed addition.
clean oil of 1a which is NMR spectroscopically pure (12.1 g, 98%
yield) (Eq. 1).18
Supplementary data
PMe3/THF(2.5 mL)
(MeO)2P(O)H
5.5 g
P(O)(OMe)2
6.8 g
+
1a
Supplementary data (a list of analytical and spectral data of the
adducts; copies of 1H, 13C and 31P NMR spectra) associated with
this article can be found, in the online version, at http://dx.doi.
org/10.1016/j.tetlet.2015.07.077.
1. 0 °C, 0.5 h; 25 °C, 20 h
2. vaccum (1 mmHg, 2.0 h)
12.1 g (98% yield)
ð1Þ
This PMe3-catalyzed addition reaction can be readily applied to
other substrates to efficiently produce the corresponding bisphos-
phorylethanes in high yields (Table 3). Thus, in addition to
dimethyl vinylphosphinate (entry 1), dimethyl phosphite effi-
ciently added to dibutyl vinylphosphonate to produce the unsym-
metrical bisphosphorylethane quantitatively (entry 2). Not limited
to vinylphosphonates (entries 1–3), vinylphosphinates (entries 4
and 5) and a vinylphosphine oxide (entry 6) could also be used
as the substrates to produce the corresponding adducts in high
yields. As to the >P(O)H compounds, as shown in Table 3, in
addition to H-phosphonates (entries 1–6), H-phosphinates (entries
7 and 8) and secondary phosphine oxides (entries 10–14) all could
be used as the substrates to produce the corresponding adducts
efficiently.
References and notes
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As exemplified by Eq. 2, by using this PMe3-catalyzed addition,
a tridentate phosphorus compounds could be easily synthesized in
85% isolated yield. This tridentate phosphorus compound are start-
ing materials for the synthesis of other tridentate phosphorus
compounds.
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O
O
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P
O
P
(MeO)2P
P(OMe)2
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PMe3 (0.05 mmol)
THF (1 mL)
(MeO)2P(O)H
1 mmol
+
20 h, 25 o
C
0.5 mmol
85% isolated yield
ð2Þ
17. After 18 h, addition product 1 was obtained in 92% (Et3P) and 89% (n-Bu3P),
respectively when (Et3P) or (n-Bu3P) was used instead of Me3P.
18. The complete removal of PMe3 was confirmed by using 1H and 31P NMR
spectroscopies.
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5935–5937.
The detailed mechanism for this reaction was not clear.
However, since trimethylphosphine can easily add to a vinylphos-
phoryl compound to generate a phosphonium intermediate 4,19 we
consider that this catalytic reaction should take place via a cycle as
shown in Scheme 2. Thus, the phosphonium intermediate 4, gener-
ated by the addition of PMe3 to 3, was protonated by 2, and PMe3