Efficient one-pot synthesis of β-hydroxyphosphonates: regioselective nucleophilic ring opening reaction of epoxides with triethyl phosphite catalyzed by Al(OTf)3

Article abstract of DOI:10.1016/j.tet.2009.06.106

A variety of β-hydroxyphosphonates were produced in high yields by ring opening reaction of different types of epoxides with di/trialkyl phosphite esters catalyzed by Al(OTf)₃. The reactions proceeded with complete chemo- and regioselectivity t

Full text of DOI:10.1016/j.tet.2009.06.106

Tetrahedron 65 (2009) 7691–7695
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Tetrahedron
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Efficient one-pot synthesis of b-hydroxyphosphonates: regioselective nucleophilic
ring opening reaction of epoxides with triethyl phosphite catalyzed by Al(OTf)3
*
Sara Sobhani , Asieh Vafaee
Department of Chemistry, College of Sciences, Birjand University, Birjand 414, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of b-hydroxyphosphonates were produced in high yields by ring opening reaction of different
Received 22 January 2009
Received in revised form 9 June 2009
Accepted 25 June 2009
types of epoxides with di/trialkyl phosphite esters catalyzed by Al(OTf)3. The reactions proceeded with
complete chemo- and regioselectivity to give the title compounds. This method is new, simple and ef-
ficient for the one-pot synthesis of
b-hydroxyphosphonates via direct C–P bond formation.
Available online 2 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
epoxides,27 miosture sensitive catalysts or reagents,28–32 drastic
reaction conditions,28 strong bases,29 stoichiometric amounts of
the catalyst30–32 and the formation of by-products (e.g. cyclo-
propane or olefin).26,33
Amongst phosphonates,
b-hydroxyphosphonates are an im-
portant class of compounds. They exhibit a variety of interesting
and useful properties that make them attractive as herbicides, an-
tibiotics, pesticides, antioxidants and horticulture agents.1–6 Many
of these diverse properties have been attributed to the relatively
inert nature of the C–P bond and to the physical and structural
similarity of phosphonic and phosphinic acids to the biologically
important phosphate ester and carboxylic acid functional groups.7
In recent years, we have focused our attention on the de-
velopment of useful methods for the synthesis of phosphonate
derivatives.34–39 In this connection, we have found that metal tri-
flates [M(OTf)x; M¼Al, Li, Mg, Ce, Cu] are efficient catalysts for the
synthesis of
a-amino-,
a
-trimethylsilyloxy- and
a-acyloxy-
phosphonates.40–45 These observations prompted us to examine
the catalytic efficiency of these metal triflates for the one-pot
Furthermore,
preparation of different types of phosphonate derivatives such as:
-unsaturated,8 -azido-,9 -amino-,9 -tosyloxy-,10 and
-acyl-
oxyphosphonates.11
-Acyloxyphosphonates have been also used
b-hydroxyphosphonates serve as precursors for the
synthesis of b-hydroxyphosphonates by a ring opening reaction of
epoxides with triethyl phosphite.
a
,b
b
b
b
b
b
as intermediates in the synthesis of optically active
b-hydroxy-
2. Results and discussion
phosphonates by enzymetic hydrolysis.12
There are several multistep approaches for the synthesis of
hydroxyphosphonates: a) reduction of
-ketophosphonates,13–18
b) oxidation of the
-H in alkylphosphonates,19 c) hydrolysis of
acyl derivatives,20 d) reaction of some Grignard reagents with
b
-
At first, we examined the feasibility of the ring opening reaction
of glycidyl phenyl ether (1a) with triethyl phosphite (molar ratio:
1/5) using metal triflates [M(OTf)x; M¼Al, Li, Mg, Ce, Cu] in n-hexane
under reflux conditions. Amongst metal triflates tested, Al(OTf)3
turned out to be the most effective catalyst for this purpose (Table 1,
Entry 1). The desired product (2a) was obtained in lower yields and
after longer reaction times, when 1 or 3 equiv of triethyl phosphite
were used (Table 1, Entries 2 and 3). The reaction proceeded with
low yields in solvents such as toluene, CCl4, or CH3CN under reflux
conditions (Table 1, Entries 8–10). No yields were obtained when
the reaction was carried out in CH2Cl2, Et2O or acetone as solvent
(Table 1, Entries 11–13). A similar reaction in the absence of solvent
led to the formation of the desired product (2a) in low yield due to
the formation of a mixture of by-products (Table 1, Entry 14).
In the next step, the applicability of this method for the ring
opening reaction of various types of epoxides with triethyl phosphite
using Al(OTf)3 in n-hexane under reflux condition were investigated
(Scheme 1). The results of these studies are summarized in Table 2.
b
b
b
a
-ketophosphonates21 and e) Reformatsky-type addition of
-halophosphonates to carbonyl compounds.22–24
-Hydroxy-
b
phosphonates can also be prepared by one-pot reaction via direct
C–P bond formation of phosphite esters with epoxides in the
presence of acids or bases. These methods are similar to Arbuzov
reaction of alkyl halides with phosphite esters.25 However, a few
reported methods exist for the one-pot synthesis of b-hydroxy-
phosphonates26–32 and all of these methods suffer from at least
one of the following drawbacks: low yields,26 the use of excess of
* Corresponding author. Tel.: þ98 561 2502008; fax: þ98 561 2502009.
E-mail addresses: ssobhani@birjand.ac.ir, sobhanisara@yahoo.com (S. Sobhani).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.06.106

7692
S. Sobhani, A. Vafaee / Tetrahedron 65 (2009) 7691–7695
Table 1
Table 2
Ring opening reaction of glycidyl phenyl ether with triethyl phosphite catalyzed by
Al(OTf)3 catalyzed ring opening reaction of various types of epoxides with tri-
different metal triflates M(OTf)x [M¼Al, Li, Mg, Ce, Cu]
ethylphosphite in n-hexane under reflux conditions
Entry
Catalyst
Solvent
Temp.
Time (h)
Yielda (%)
Entry
1
Epoxide
Product
Yielda (%)
1
2
3
4
5
6
7
8
Al(OTf)3
Al(OTf)3
Al(OTf)3
LiOTf
n-hexane
n-Hexane
n-hexane
n-Hexane
n-Hexane
n-Hexane
n-Hexane
Toluene
CCl4
CH3CN
CH2Cl2
Et2O
Acetone
d
Reflux
Reflux
Reflux
Reflux
Reflux
reflux
Reflux
Reflux
Reflux
Reflux
rt
0.75
2
10
10
10
3
18
72
72
72
24
24
24
0.25
93
90d
85d
8
12
40
0
O
O
OH
O
P(OEt)2
O
93
Mg(OTf)2
Ce(OTf)4
Cu(OTf)2
Al(OTf)3
Al(OTf)3
Al(OTf)3
Al(OTf)3
Al(OTf)3
Al(OTf)3
Al(OTf)3
2a
1a
O
OH
O
20
10
40
0c
Cl
P(OEt)2
Cl
2
3
88
86
9
1b
10
11
12
13
14
2b
0c
O
OH
rt
rt
O
0c
O
O
P(OEt)2
80 ꢀ
C
40b
a
O
Isolated yield. Conditions: triethyl phosphite (5 equiv, except for entries 2 and 3),
catalyst (10 mol %).
1c
2c
O
b
Conversion of epoxide was 100% but desired product besides a mixture of by-
O
OH
O
products were formed.
c
100% Consumption of epoxide was observed but a mixture of by-products were
O
P(OEt)2
O
4
5
95
93
formed.
d
Conditions: triethyl phosphite (3 and 1 equiv for entries 2 and 3, respectively).
1d
2d
OH
O
O
O
OH
O
O
O
P(OEt)2
Al(OTf)3 (10 mol%)
P(OEt)2
+
P(OEt)3
1e
n-hexane, reflux
R
R
2e
1a-h
2a-h
O
P(OEt)2
Scheme 1. Al(OTf)3 catalyzed ring opening reaction of epoxides with
triethylphosphite.
O
6
7
98b
It is worthy of mention that Al(OTf)3 was used as an efficient
catalyst for the ring opening reaction of epoxides by oxygen and
nitrogen nucleophiles in recent years.46–48 To the best of our
knowledge, there is no report in the literature on the conversion of
OH
1f
2f
O
OH
O
P(OEt)2
98
95
epoxides to b-hydroxyphosphonates by phosphorus nucleophiles
in the presence of Al(OTf)3.
As indicated in Table 2, the reactions of different types of
epoxides with triethyl phosphite proceeded with complete regio-
2g
1g
O
O
OH
P(OEt)2
8
selectivity to afford the corresponding
b-hydroxyphosphonates
(2a–h) in high yields. No by-product was formed in any of these
transformations. Moreover, the results show that triethyl phosphite
attacked the epoxide ring even in the presence of functional groups
susceptible to Arbuzov reaction and Michael addition (Entries 2 and 3).
These observations are a good indication of the presence of an
excellent chemoselectivity in this method.
1h
2h
a
Isolated yield. All products gave satisfactory spectral data in accordance with the
known literature data.10,11,26–32,49,50
b
dr¼100%, trans isomer is formed.10
All the products were isolated and identified by their
EtO
EtO
O
H
O
spectral data such as 1H NMR, 13C NMR, 31P NMR, IR and MS. The
b
P
O
H
O
H
-hydroxyphosphonates (2a–h) exist predominantly as their anti-
H
H
EtO
CH2X
P
conformers 3a–h (Scheme 2) as can be juged from the large values
3
H
H
of their JC,P couplings (15.5–20.1 Hz). The predominant formation
OEt
H
of the anti conformer 3a–h can be a result of the hydrogen bond
formation within a six-membered ring. It adopts a chair confor-
mation (4a–h) with C-3 substituents in the equatorial positions
(Scheme 2).50 These obervations are in agreement with the for-
mation of the regioisomer resulting from the nucleophilic attack on
the less substituted carbon of the epoxide. Appearance of a signal at
1.61–2.35 ppm with the integration equivalent to two hydrogens in
1H NMR spectrum of the products is another indication for this
regioiomer formation.
All mass spectral data consist of molecular peaks with weak
intensities due to the readily cleavage of C2–C3 bond followed by
loss of two fragments of C2H4 (Scheme 3). The appearance of two
peaks at m/e¼181 and 125 are the results of the above mentioned
cleavages. These two peaks are observed as common peaks in mass
spectra of all the products except for 2f (Mþþ1¼237, 100%).
CH2X
3a-h
4a-h
Scheme 2. anti and Chair conformers of the products.
H
H
O
O
H
O
O
P
XH2C
m/e=181
m/e=125
Scheme 3. Common fragmentation of
b
-hydroxyphosphonates.

S. Sobhani, A. Vafaee / Tetrahedron 65 (2009) 7691–7695
7693
After performing the preparation reaction of diethyl
b
-hydroxy-
the absence of Al(OTf)3, the starting materials remain intact even
after prolonged reaction times (Table 3).
Furthermore, we have evaluated the generality of the presented
method for the ring opening reaction of glycidyl phenyl ether with
different phosphite esters (Scheme 4). The results of these studies
are presented in Table 4.
phosphonate 2a under the conditions described in Table 2, the
reaction mixture was washed with water. The aqueous layer con-
taining the catalyst was separated. Evaporation of the solvent under
reduced pressure gave the catalyst, which was re-used for a con-
secutive run under the same reaction conditions. The average iso-
lated yields of 2a and the catalyst for five consecutive runs were 90.8
and 96.8, respectively (Fig.1). This reusability demonstrates the high
stability and turnover of Al(OTf)3 under the employed conditions. It
is noteworthy that the recyclability test was stopped after five runs.
O
OH
O
P(OR')3
or
HP(O)(OR')2
O
P(OR')2
O
Al(OTf)3 (10 mol%)
+
n-hexane, reflux
2a, 3a, 4a
2a
Catalyst
1a
R'=Et, iso-Pr., Ph
100
80
60
40
20
0
Scheme 4. Ring opening reaction of glycidyl phenyl ether with various phosphite
esters.
Table 4
Ring opening reaction of glycidyl phenyl ether with various phosphite esters cata-
lyzed by Al(OTf)3 in n-hexane under reflux conditions
Entry
Phosphitea
Product
Time (min)
Yieldb (%)
1
2
3
4
5
P(OEt)3
2a
3a
2a
3a
4a
45
60
45
120
50
93
90
96
92
97
P(O-i-Pr)3
HP(O)(OEt)2
HP(O)(O-i-Pr)2
P(OPh)3
1
2
3
4
5
a
Conditions: phosphite (5 equiv), Al(OTf)3 (10 mol %).
Isolated yield.
b
Figure 1. Reusability of Al(OTf)3 as a catalyst for the synthesis of 2a.
As is obvious from Table 4, the catalytic ring opening reaction of
glycidyl phenyl ether proceeded well with different nucleophilic
phosphite esters such as tri-iso-propyl/triphenyl phosphite and
diethyl/di-iso-propyl phosphite as well as triethyl phosphite.
We have also compared the catalytic activity of Al(OTf)3 with
some common Lewis acids [e.g. Al(OH)3, AlCl3, FeCl3, I2, LiClO4,
ZrCl4], BrØnsted acids [e.g. TfOH, HClO4, H3PW12O40, NH2SO3H] and
metal oxides [e.g. CdO, Sb2O3, SnO, PbO, MoO3, W2O3, ZnO] for the
ring opening reaction of glycidyl phenyl ether with triethyl phos-
phite in refluxing n-hexane (Table 3). As it is evident from Table 3,
Al(OTf)3 is the most effective catalyst for this purpose leading to the
3. Conclusion
In conclusion, Al(OTf)3 was found as a re-usable and efficient
formation of diethyl b-hydroxyphosphonate 2a in high yields. In
catalyst for the one-pot synthesis of a variety of
b-hydroxy-
phosphonates by ring opening reaction of epoxides with different
phosphite esters. This method not only provides a novel protocol for
Table 3
the synthesis of biologically important b-hydroxyphosphonates, but
Comparison of the catalytic efficiency of Al(OTf)3 with various catalysts in the re-
action of glycidyl phenyl ether with triethyl phosphitea
also extends the applicability of Al(OTf)3 for the ring opening re-
action of epoxides by phosphorus nucleophiles. High yields, excel-
lent chemo- and regioselectivity, easy work-up, no by-product
formationandusingacatalyticamountofAl(OTf)3 makethismethod
attractive and a useful contribution to the present methodologies.
Entry
Catalystb
Time (h)
Yieldc (%)
1
2
3
Al(OTf)3
Al(OH)3
AlCl3
1
24
9
93
47e
20
4
FeCl3
2
35
5
6
7
8
I2
LiClO4
ZrCl4
24
24
5
0
40g
15g
0
4. Experimental
4.1. General
TfOH
9
9
HClO4
H3PW12O40
NH2SO3H
CdOd
0.25
df
2
50g
0e
10
11
12
13
14
15
16
17
18
19
50g
Trace
0e
Chemicals were purchased from Merck and Fluka Chemical
Companies. All of the products were identified by their physical and
spectral data. IR spectra were run on a Perkin Elmer 780 instrument.
NMR spectra were recorded in ppm in CDCl3 on a Bruker Avance
DPX-250 instrument using TMS as an internal standard for 1H NMR
and 13C NMR and 85% H3PO4 as an external standard for 31P NMR.
Mass spectra were recorded on a Shimadzu GC–MS-QP5050A. Ele-
mental analysis for C, H and N were obtained using a Heraeus CHN-
O-Rapid analyzer. The purity of the products and the progress of the
reactions were accomplished by TLC on silica-gel polygram SILG/
UV254 plates or by GC on Shimadazu model GC-14A instrument.
48
24
24
24
48
24
24
72
d
Sb2O3
SnOd
PbOd
0e
0e
d
MoO3
15
0e
d
W2O3
ZnOd
d
0 (40)g,h
0
a
Conditions: at reflux in n-hexane (except for entry 19). triethyl phosphite
(5 equiv).
b
Catalyst (10 mol %).
c
Isolated yield.
d
e
Catalyst (100 mol %).
100% Consumption of epoxide was observed but a mixture of by-products was
4.2. General procedure for the preparation of
hydroxyphosphonates (2a–h, 3a and 4a)
b-
observed.
f
Immediately.
g
100% Consumption of epoxide was observed but the desired product besides
Al(OTf)3 (0.01 mmol) was added to a solution of epoxide
(1 mmol) and P(OEt)3 (5 mmol) in n-hexane (5 ml). The reaction
a mixture of by-products was obtained.
h
Diethyl phosphite (5 equiv) was used.

7694
S. Sobhani, A. Vafaee / Tetrahedron 65 (2009) 7691–7695
3
mixture was stirred at reflux conditions for 1 h and then washed
with water (2ꢁ10 mL). The organic layer was separated and dryed
over anhydrous Na2SO4. Evaporation of the solvent under reduced
pressure gave the crude product. The pure product was isolated by
chromatography on silica gel.
(CH2]CH), 73.8 (d, JC,P¼15.7 Hz, CH2), 72.2 (CH2), 65.6 (d,
2JC,P¼4.0 Hz, CHOH), 61.9 [d, JC,P¼6.2 Hz, P(O)(OCH2CH3)2], 61.8
2
2
1
[d, JC,P¼6.2 Hz, P(O)(OCH2CH3)2], 30.1 (d, JC,P¼139.6 Hz, CH2P),
3
16.3 [d, JC,P¼6.2 Hz, P(O)(OCH2CH3)2]; dP (101.2 MHz, CDCl3):
30.34; m/z 253 (10.86Mþþ1), 181 (89.11), 125 (100), 64 (47.01), 41
(61.42%).
4.3. Spectral data for diethyl 2-hydroxyphosphonates (2a–h,
3a and 4a)
4.3.6. Diethyl 2-hydroxycyclohexylphosphonate (2f)
Pale yellow oil; Rf (50% n-hexane/EtOAc) 0.25; ymax (neat): 3448
4.3.1. Diethyl 2-hydroxy-3-phenoxypropylphosphonate (2a)
Pale yellow oil; Rf (50% n-hexane/EtOAc) 0.25; ymax (neat): 3320
(–OH) cmꢂ1
;dH (250 MHz,CDCl3):4.07–3.98[m, 5H, P(O)(OCH2CH3)2,
OH], 3.64–3.61 (m,1H, CHOH), 2.00–1.61 (m, 5H, CHP, CH2),1.29–1.20
[m, 10H, P(O)(OCH2CH3)2, CH2]; dC (62.9 MHz, CDCl3): 68.7 (d,
(–OH) cmꢂ1
; dH (250 MHz, CDCl3): 7.31–7.25 (m, 2H, Ar), 6.99–6.89
2
(m, 3H, Ar), 4.46–4.34 (m, 1H, CHOH), 4.26–4.14 [m, 4H,
P(O)(OCH2CH3)2], 4.06–3.94 (m, 2H, CH2), 2.32–2.23 (m, 1H, CH2P),
2.20–2.07 (m, 1H, CH2P), 1.48–1.25 [m, 6H, P(O)(OCH2CH3)2]; dC
(62.9 MHz, CDCl3): 158.3, 129.5, 121.2, 114.5 (Ar), 71.2 (d,
2JC,P¼5.5 Hz, CHOH), 62.1 [d, JC,P¼6.2 Hz, P(O)(OCH2CH3)2], 61.8 [d,
2JC,P¼6.2 Hz, P(O)(OCH2CH3)2], 43.2 (d, 1JC,P¼135.2 Hz, CHP), 34.5 (d,
3JC,P¼15.5 Hz, CH2), 25.1 (d, 3JC,P¼19.5 Hz, CH2), 25.0, 24.1 (CH2), 16.4
[d, 3JC,P¼5.5 Hz, P(O)(OCH2CH3)2], 16.3 [d, 3JC,P¼5.5 Hz,
P(O)(OCH2CH3)2]; dP (101.2 MHz, CDCl3): 32.39; m/z 237 (100Mþþ1),
165 (90.02%).
2
3JC,P¼15.7 Hz, CH2), 65.4 (d, JC,P¼4.0 Hz, CHOH), 62.1 [d,
2JC,P¼5.7 Hz,
P(O)(OCH2CH3)2],
62.0
[d,
2JC,P¼5.7 Hz,
P(O)(OCH2CH3)2],
30.2
(d,
1JC,P¼140.5 Hz,
CH2P),
16.4
[P(O)(OCH2CH3)2]; dP (101.2 MHz, CDCl3): 30.16; m/z 289
4.3.7. Diethyl 2-hydroxyhex-5-enylphosphonate (2g)
(6.58Mþþ1), 288 (1.46Mþ), 181 (83.54), 125 (100%).
Pale yellow oil; [Found: C, 50.70; H, 8.82. C10H21O4P requires C,
50.84; H, 8.96%]; Rf (50% n-hexane/EtOAc) 0.25; ymax (neat): 3473
4.3.2. Diethyl 3-chloro-2-hydroxypropylphosphonate (2b)
(–OH) cmꢂ1
; dH (250 MHz, CDCl3): 5.85–5.69 (m, 1H, CH2]CH),
Pale yellow oil; Rf (50% n-hexane/EtOAc) 0.25; ymax (neat):
5.03–4.91 (m, 2H, CH2]CH), 4.22–4.04 [m, 5H, P(O)(OCH2CH3)2,
CHOH], 3.75 (br s, –OH), 2.19–2.00 (m, 4H, CH2P, CH2), 1.71–1.52 (m,
3516 (–OH) cmꢂ1
; dH (250 MHz, CDCl3): 4.33–4.25 [m, 5H,
3
P(O)(OCH2CH3)2, CHOH], 4.02 (br s, OH), 3.61–3.59 (m, 2H,
2H, CH2), 1.31 [t, 6H, JH,H¼7.0 Hz, P(O)(OCH2CH3)2]; dC (62.9 MHz,
3
2
CH2Cl), 2.35–2.25 (m, 2H, CH2P), 1.36 [t, 6H, JH,H¼6.7 Hz,
CDCl3): 137.8 (CH2]CH), 115.0 (CH2]CH), 65.7 (d, JC,P¼6.3 Hz,
2
P(O)(OCH2CH3)2]; dC (62.9 MHz, CDCl3): 66.3 (d, JC,P¼5.0 Hz,
CHOH), 63.4 [d, 2JC,P¼6.3 Hz, P(O)(OCH2CH3)2], 63.3 [d, 2JC,P¼6.3 Hz,
P(O)(OCH2CH3)2], 37.5 (d, 3JC,P¼17.0 Hz, CH2), 33.5 (d,1JC,P¼140.9 Hz,
2
CHOH), 64.4 [d, JC,P¼7.5 Hz, P(O)(OCH2CH3)2], 64.2 [d,
3
3
2JC,P¼7.5 Hz, P(O)(OCH2CH3)2], 49.1 (d, JC,P¼20.1 Hz, CH2Cl),
CH2P), 29.6 (CH2), 16.2 [d, JC,P¼6.3 Hz, P(O)(OCH2CH3)2]; dP
30.7 (d, 1JC,P¼145.5 Hz, CH2P), 16.2 [d, 3JC,P¼6.3 Hz,
P(O)(OCH2CH3)2]; dP (101.2 MHz, CDCl3): 31.13; m/z 233
(4.17Mþþ3), 231 (12.59Mþþ1), 195 (2.80), 181 (65.52), 125 (100),
43 (24.10%).
(101.2 MHz, CDCl3): 32.06; m/z 237 (15.76Mþþ1), 181 (74.21), 125
(100), 99 (8.54), 82 (12.15), 41 (20.47%).
4.3.8. Diethyl 2-hydroxyoctylphosphonate (2h)
Pale yellow oil; [Found: C, 54.01; H, 10.00. C12H27O4P re-
quires C, 54.12; H, 10.22%]; Rf (50% n-hexane/EtOAc) 0.25; ymax
4.3.3. 3-(Diethylphosphoryl)-2-hydroxypropyl methacrylate (2c)
Pale yellow oil; Rf (30% n-hexane/EtOAc) 0.25; ymax (neat): 3562
(neat): 3512 (–OH) cmꢂ1
; dH (250 MHz, CDCl3): 4.20–3.85 (m,
(–OH) cmꢂ1
;
dH (250 MHz, CDCl3): 6.17 (s, 1H, CH2]C), 5.61 (s, 1H,
5H, CHOH, P(O)(OCH2CH3)2], 3.36 (br s, OH), 2.00–1.85 (m, 2H,
CH2P), 1.50–1.24 [m, 16H, P(O)(OCH2CH3)2, CH2], 0.83 (t, 3H,
CH2]C), 4.31–4.06 [m, 8H, P(O)(OCH2CH3)2, CHOH, CH2, –OH],
2.34–2.10 (m, 2H, CH2P), 1.96 (s, 3H, CH3), 1.41–1.35 [m, 6H,
P(O)(OCH2CH3)2]; dC (62.9 MHz, CDCl3): 167.7 (C]O), 135.6
(CH2]C), 126.5 (CH2]C), 68.1 (CHOH), 65.3 (d, 3JC,P¼17.0 Hz, CH2),
2
3JH,H¼7.0 Hz, CH3); dC (62.9 MHz, CDCl3): 66.4 (d, JC,P¼4.5 Hz,
2
CHOH), 61.8 [d, JC,P¼5.7 Hz, P(O)(OCH2CH3)2], 38.2 (d,
1
3JC,P¼17.0 Hz, CH2), 33.4 (d, JC,P¼138.0 Hz, CH2P), 31.7, 28.9,
1
3
63.9 P(O)(OCH2CH3)2], 38.7 (d, JC,P¼144.0 Hz, CH2P), 18.3
25.3, 22.5 (CH2), 16.4 [d, JC,P¼6.3 Hz, P(O)(OCH2CH3)2], 14.0
(C]CCH3), 16.1 [P(O)(OCH2CH3)2]; dP (101.2 MHz, CDCl3): 31.5; m/z
279 (4.36Mþꢂ1), 181 (68.76), 125 (100%).
(CH3); dP (101.2 MHz, CDCl3): 31.56; m/z 267 (12.43, Mþþ1), 181
(100), 125 (74.22), 43 (20.96%).
4.3.4. Diethyl 2-hydroxy-3-isopropoxypropylphosphonate (2d)
Pale yellow oil; Rf (50% n-hexane/EtOAc) 0.25; ymax (neat): 3394
4.3.9. Diisopropyl 2-Hydroxy-3-phenoxypropylphosphonate (3a)
Pale yellow oil; Rf (50% n-hexane/EtOAc) 0.25; ymax (neat): 3266
(–OH) cmꢂ1
;
dH (250 MHz, CDCl3): 4.13–4.08 [m, 5H,
(–OH) cmꢂ1
; dH (250 MHz, CDCl3): 7.31–7.25 (m, 2H, Ar), 6.98–6.90
P(O)(OCH2CH3)2, OH], 3.58–3.48 [m, 2H, CH(CH3)2, CHOH], 3.34 (d,
(m, 3H, Ar), 4.79–4.69 [m, 2H, P(O)(OCH(CH3)2)2], 4.45–4.25 (m,
1H, CHOH), 4.03–3.94 (m, 2H, CH2), 3.73 (br s, OH), 2.23–1.95 (m,
3
2H, JH,H¼5.0 Hz, CH2), 2.08–1.96 (m, 2H, CH2P), 1.25 [t, 6H,
3JH,H¼7.5 Hz, P(O)(OCH2CH3)2], 1.06 [d, 6H, 3JH,H¼6.3 Hz, CH(CH3)2];
2H, CH2P), 1.34 [d, 12H, JH,H¼5.2 Hz, P(O)(OCH(CH3)2)2]; dC
2
3
dC (62.9 MHz, CDCl3): 72.1 [CH(CH3)2], 71.9 (d, JC,P¼16.3 Hz, CH2),
(62.9 MHz, CDCl3): 158.4, 129.4, 121.1, 114.5 (Ar), 71.3 (d,
65.5 (d, 2JC,P¼4.4 Hz, CHOH), 62.8 [d, 2JC,P¼6.3 Hz, P(O)(OCH2CH3)2],
3Jc,p¼15.7 Hz, CH2), 70.9 [d, JC,P¼5.0 Hz, P(O)(OCH(CH3)2)2], 70.8
2
2
1
2
2
62.7 [d, JC,P¼6.3 Hz, P(O)(OCH2CH3)2], 30.3 (d, JC,P¼111.5 Hz,
[d, JC,P¼5.0 Hz, P(O)(OCH(CH3)2)2], 65.5 (d, JC,P¼5.0 Hz, CHOH),
3
1
CH2P), 21.9 [CH(CH3)2], 16.2 [d, JC,P¼6.3 Hz, P(O)(OCH2CH3)2]; dP
31.1 (d, Jc,p¼184.6 Hz, CH2P), 24.0 [P(O)(OCH(CH3)2)2]; dP
(101.2 MHz, CDCl3): 31.49; m/z 253 (3.06Mþꢂ1), 181 (46.22), 125
(101.2 MHz, CDCl3): 28.06; m/z 317 (16.14, Mþþ1), 209 (17.37), 125
(64.88), 57 (51.46), 43 (100%).
(100), 43 (21.89%).
4.3.5. Diethyl 3-(allyloxy)-2-hydroxypropylphosphonate (2e)
Pale yellow oil; Rf (50% n-hexane/EtOAc) 0.25; ymax (neat):
4.3.10. Diphenyl 2-hydroxy-3-phenoxypropylphosphonate (4a)
Brown-red oil; Rf (10% n-hexane/CH2Cl2) 0.35; ymax (neat):
3464 (–OH) cmꢂ1
;
dH (250 MHz, CDCl3): 5.93–5.77 (m, 1H,
3387 (–OH) cmꢂ1
; dH (250 MHz, CDCl3): 7.3–7.1 (m, 7H, Ar), 6.92–
CH2]CH), 5.26–5.12 (m, 2H, CH2]CH), 4.13–3.97 [m, 7H, CHOH,
6.82 (m, 8H, Ar), 4.30–4.15 (m, 2H, CH2), 4.10–3.85 (m, 2H, CHOH,
OH), 2.95–2.65 (m, 2H, CH2P); dC (62.9 MHz, CDCl3): 158.4, 156.6,
3
CH2, P(O)(OCH2CH3)2], 3.42 (d, 2H, JH,H¼5.0 Hz, CH2), 3.19 (br s,
3
3
OH), 2.01–1.91 (m, 2H, CH2P), 1.28 [t, 6H, JH,H¼7.0 Hz,
155.6, 129.5, 121.3, 120.6, 115.3, 114.5 (Ar), 68.7 (d, Jc,p¼18.9 Hz,
1
P(O)(OCH2CH3)2]; dC (62.9 MHz, CDCl3): 134.4 (CH2]CH), 117.2
CH2), 65.9 (CHOH), 29.7 (d, JC,P¼140.0 Hz, CH2P); dP (101.2 MHz,

S. Sobhani, A. Vafaee / Tetrahedron 65 (2009) 7691–7695
7695
CDCl3): 22.47; m/z 384 (2.75, Mþ), 366 (4.11), 326 (45.56), 77
(100%).
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Acknowledgements
We are thankful to Birjand University Research Council for their
support on this work. We would like to thank Dr. M. Bella for his
helpful discussion.
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