A new, efficient, and simple method for the one-pot synthesis of α-acetoxyphosphonates from aldehydes under solvent-free conditions

Article abstract of DOI:10.1016/j.bmcl.2006.07.083

A simple, efficient, and new method has been developed for the synthesis of α-acetoxyphosphonates from aldehydes through a one-pot reaction of aldehydes with diethylphosphite in the presence of acetic anhydride under solvent-free conditions using magnesiu

Full text of DOI:10.1016/j.bmcl.2006.07.083

Bioorganic & Medicinal Chemistry Letters 16 (2006) 5324–5327
A new, efficient, and simple method for the one-pot
synthesis of a-acetoxyphosphonates from aldehydes
under solvent-free conditions
Babak Kaboudin* and Masoumeh Karimi
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45195-1159, Iran
Received 22 May 2006; revised 9 July 2006; accepted 26 July 2006
Available online 9 August 2006
Abstract—A simple, efficient, and new method has been developed for the synthesis of a-acetoxyphosphonates from aldehydes
through a one-pot reaction of aldehydes with diethylphosphite in the presence of acetic anhydride under solvent-free conditions
using magnesium oxide. This method is easy, rapid, and high yielding for the one-pot synthesis of a-acetoxyphosphonates from
aldehydes.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Organophosphorus compounds have found a wide
range of application in the areas of industrial, agricul-
tural, and medicinal chemistry owing to their biological
and physical properties as well as their utility as synthet-
ic intermediates.1 a-Functionalized phosphonic acids are
valuable intermediates for the preparation of medicinal
compounds and synthetic intermediates.2–4 Among of
a-functional phosphonic acids, a-acetoxyphosphonates
and a-hydroxyphosphonates are an important class of
compounds that exhibit a variety of interesting and use-
ful properties. In recent years, the preparation of a-acet-
oxy and a-hydroxyphosphonates has attracted a great
deal of attention due to their potential biological activ-
ities with broad applications as enzyme inhibitors or
as dinucleotide analogues having antiviral properties.5
In addition, they are useful intermediates in the synthe-
sis of other phosphorus compounds.6 These compounds
may also be used as precursors for the synthesis of opti-
cally active a-hydroxyphosphonates.7 Indeed, a-acet-
oxyphosphonates are also used as precursors for the
synthesis of a variety of a-substituted phosphonates.
In contrast to the widely studied a-hydroxyphosphonic
acid derivatives,8–10 relatively few papers have been
reported on the chemistry of a-acetoxyphosphonates.5
Many effective methods for the preparation of
a-hydroxyphosphonates have been developed, but, to
the best of our knowledge, few synthetic routes to
a-acetoxyphosphonates have been reported. These
methods involve prolonged heating of acyl phosphates
with carbonyl compounds at 120 ꢁC,11 direct acetylation
of a-hydroxyphosphonates with ketenes catalyzed by
BF3.OEt12 or H2SO4,13 and acetylation of a-hydrox-
yphosphonates with Ac2O or AcCl in the presence of
Et3N or pyridine as a base.5a,7,14 Recently, new methods
have been reported using copper triflate as a catalyst and
microwave irradiation for the preparation of a-acet-
oxyphosphonates from the reaction of a-hydroxy-
phosphonates with Ac2O.15 However, these methods
have problems, including harsh reaction conditions,
low yields, long reaction times, use of Lewis acids, and
side reactions. On the other hand in all methods, each
of the starting materials requires prior synthesis.
Surface-mediated solid-phase reactions are of growing
interest16 because of their advantages of ease of set up,
mild conditions, rapid reactions, selectivity, increased
yields of the products, and low cost compared with their
homogeneous counterpart. As part of our efforts to
explore the utility of solid-phase reactions for the syn-
thesis of organophosphorus compounds,17 we report a
new method for the one-pot synthesis of a-acet-
oxyphosphonates from the reaction of diethylphosphite
with aldehydes in the presence of Ac2O under solvent-
free conditions, using MgO as a solid phase producing
good to high yields of a-acetoxyphosphonates (Scheme 1,
Table 1).
Keywords: Aldehydes; Magnesia; Solvent-free; Phosphorylation;
Acetic anhydride.
*
Corresponding author. Tel.: +98 241 4153220; fax: +98 241
4249023; e-mail: kaboudin@iasbs.ac.ir
0960-894X/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2006.07.083

B. Kaboudin, M. Karimi / Bioorg. Med. Chem. Lett. 16 (2006) 5324–5327
5325
O
References and notes
1. Engel, R. Chem. Rev. 1977, 77, 349.
O
C
O
H
C
MgO
2-4 h
Ac2O
P(OEt)2 +
R
P(OEt)2
R
H
+ H
2. Dingwall, J. G.; Campell, C. D.; Baylis, E. K. UK Patent
Appl., 1 542 938, 1979; Chem. Abstr. 1979, 88, 105559j.
3. Kafarski, P.; Lejczak, B.; Tyka, R.; Koba, L.; Pliszc-
zak, E.; Wieczorek, P. J. Plant Growth Regul. 1995, 14,
199.
OAc
1
2
Scheme 1.
4. Ishiguri, Y.; Yamada, Y.; Kato, T.; Sasaki, M.; Mukai, K.
Eur. Patent Appl., EP 82-301905, 1982; Chem. Abstr.
1983, 98, 102686u.
Table 1. Synthesis of a-acetoxyphosphonates from aldehydes using
MgO under solvent-free condition
5. (a) Li, Y.-F.; Hammerschmidt, F. Tetrahedron 1995, 51,
4933; (b) Li, Y.-F.; Hammerschmidt, F. Tetrahedron:
Asymmetry 1993, 4, 109; (c) Heisler, A.; Rabiller, C.;
Douillard, R.; Goalou, N.; Hagele, G.; Levayer, F.
Tetrahedron: Asymmetry 1993, 4, 959; (d) Khushi, T.;
O’Toole, k. J.; Sime, J. T. Tetrahedron Lett. 1993, 34,
2375; (e) Zhang, Y.; Li, J.-F.; Yuan, C.-Y. Tetrahedron
2003, 59, 473.
6. (a) Hammerschmidt, F.; Vollenkle, H. Leibigs Ann. Chem.
1989, 577; (b) Yokomatsu, T.; Shibuya, S. Tetrahedron:
Asymmetry 1992, 3, 377; (c) Baraldi, P. G.; Guarneri, M.;
Moroder, F.; Pollini, G. P.; Simoni, D. Synthesis 1982,
653; (d) Maier, L. Phosphorus, Sulfur, Silicon Relat. Elem.
1993, 76, 119; (e) McClure, C. K.; Mishra, P. K.; Grote, C.
W. J. Org. Chem. 1997, 62, 2437.
Compound
R
Reaction time (h) Yielda (%), 2
1a
1b
1b
1c
1d
1c
1d
1e
1f
C6H5–
2
2
3
2
2
2
3
3
3
2
4
3
2
3
90
86
83
80
90
75
87
85
81
83
80
65
75
72
p-CH3OC6H4–
p-CH3C6H4–
p-ClC6H4–
p-BrC6H4–
m-ClC6H4–
m-CH3OC6H4–
m-BrC6H4–
m-CH3C6H4–
o-ClC6H4–
1g
1h
1i
o-CH3C6H4–
a-Naphthyl
b-Naphthyl
Ph–CH@CH–
1j
1k
7. (a) Drescher, M.; Hammerschmidt, F.; Kahlig, H.
Synthesis 1995, 1267; (b) Eidenhammer, G.; Hammersch-
midt, F. Synthesis 1996, 748.
a Isolated yields.
8. (a) Hilderbrand, R. L. In The Role of Phosphonates in
Living Systems; CRC Press: Boca Raton, F1, 1982; (b)
Redmore, D. In Topics in Phosphorus Chemistry; Griffith,
E. J., Grayson, M., Eds.; Wiley: New York, 1976; Vol. 8.
9. (a) Pudovik, A. N.; Konovalova, I. V. Synthesis 1979, 81;
(b) Wynberg, H.; Smaardijk, Ab. A. Tetrahedron Lett.
1983, 24, 5899; (c) Blazis, V. J.; Koeller, K. J.; Spilling, C.
D. Tetrahedron: Asymmetry 1994, 5, 499; (d) Rath, N. P.;
Spilling, C. D. Tetrahedron Lett. 1994, 35, 227; (e) Blazis,
V. J.; Koeller, K. J.; Spilling, C. D. J. Org. Chem. 1995, 60,
931.
10. (a) Yokomatsu, T.; Yamagishi, T.; Shibuya, S. Tetrahe-
dron: Asymmetry 1993, 4, 1779; (b) Yokomatsu, T.;
Yoshida, Y.; Shibuya, S. J. Org. Chem. 1994, 59, 7930;
(c) Sardarian, A. R.; Kaboudin, B. Synth. Commun. 1997,
27, 543; (d) Kaboudin, B.; Nazari, R. J. Chem. Res. 2002,
291.
As shown in Scheme 1 and Table 1, the reaction of a
mixture of diethylphosphite and aromatic aldehydes
(1a–1h) with Ac2O under solvent-free condition using
MgO afforded the desired products in high yields
(2a–2h). Naphthalene carbaldehydes as polynuclear
aldehydes also reacted with diethylphosphite in the
presence of Ac2O using MgO, to give the desired com-
pounds in high yields (2i and 2j). Cinnamaldehyde
(1k) also reacted to give the desired compound 2k in
good yield.
In all the reactions we have reported in this paper
cleavage of C–P bond of the phosphonates was not
detected and the conversion of the substrates to their
corresponding acetyloxy compounds was clean.
Work-up of the reaction mixture is very easy and
gives highly pure products, which do not need further
purification.18
11. Nesterov, L. V.; Sabirova, R. A.; Krepysheva, N. E.
J. Gen. Chem. USSR (Eng. Transl.) 1969, 39, 1906.
12. McConnell, R. L.; Coover, H. W., Jr. J. Am. Chem. Soc.
1957, 79, 1961.
13. Pudovik, A. N.; Gozman, I. P.; Nikitina, V. I. J. Gen.
Chem. USSR (Eng. Transl.) 1963, 33, 3128.
In summary, in this paper, we have described a simple
procedure for the high yielding synthesis of a variety
of diethyl a-acetoxyphosphonates by one-pot reaction
of aldehydes with diethylphosphite in the presence of
acetic anhydride using magnesia. Simple work-up,
solvent-free condition, fast reaction rates, mild reac-
tion conditions, good to high yields, and the clean
reactions with no tar formation make this method
an attractive and a useful contribution to present
methodologies.
14. Strepikheev, Yu. A.; Kovalenko, L. V.; Batalina, A. V.;
Shvetsova, L. A. Deposited Doc. 1976, VINITI, 2264;
Chem. Abstr. 1978, 89, 129601.
15. (a) Firouzabadi, H.; Iranpoor, N.; Sobhani, S.; Amooz-
gar, Z. Synthesis 2004, 295; (b) Firouzabadi, H.; Iranpoor,
N.; Sobhani, S.; Amoozgar, Z. Synthesis 2004, 1771.
16. (a) Fadel, A.; Yefash, R.; Saluan, J. Synthesis 1987, 37; (b)
Rosini, G.; Galarini, R.; Marotta, E.; Righi, R. J. Org.
Chem. 1990, 55, 781; (c) Kodomari, M.; Sakamoto, T.;
Yoshitomi, S. J. Chem. Soc., Chem. Commun. 1990, 701;
(d) Kropp, P. J.; Daus, K. A.; Crawford, S. D.; Tubergren,
M. W.; Kepler, K. D.; Craig, S. L.; Wilson, V. P. J. Am.
Chem. Soc. 1990, 112, 7433; (e) Hondrogiannis, G.; Pagni,
R. M.; Kabalka, G. W.; Anisoki, P.; Kurt, R. Tetrahedron
Lett. 1990, 31, 5433; (f) Pantney, H. K. Tetrahedron Lett.
1991, 32, 2259; (g) Pauter, F.; Daudon, M. Tetrahedron
Lett. 1991, 32, 1457.
Acknowledgment
The Institute for Advanced Studies in Basic Sciences
(IASBS) is thanked for supporting this work.

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B. Kaboudin, M. Karimi / Bioorg. Med. Chem. Lett. 16 (2006) 5324–5327
17. (a) Sardarian, A. R.; Kaboudin, B. Tetrahedron Lett.
1997, 38, 2543; (b) Kaboudin, B. Chem. Lett. 2001, 880; (c)
Kaboudin, B. Tetrahedron Lett. 2000, 41, 3169; (d)
Kaboudin, B.; Nazari, R. Tetrahedron Lett. 2001, 42,
8211; (e) Kaboudin, B. Tetrahedron Lett. 2002, 43, 8713;
(f) Kaboudin, B. Tetrahedron Lett. 2003, 44, 1051; (g)
Kaboudin, B.; Rahmani, A. Org. Prep. Proced. Int. 2004,
36, 82; (h) Kaboudin, B.; Rahmani, A. Synthesis 2003,
2705; (i) Kaboudin, B.; Saadati, F. Synthesis 2004, 1249.
18. This solvent-free reaction is operationally simple. Magne-
sium oxide (1 g) was added to a stirred mixture of
diethylphosphite (0.01 mol) and aldehyde (0.01 mol) at
room temperature. Acetic anhydride (0.03 mol) was added
to this mixture which was then stirred for 2–4 h at room
temperature. The mixture was washed with ethyl acetate
(4· 50 mL), dried with CaCl2, and the solvent evaporated
to give crude product. Chromatography on silica gel with
EtOAc/n-hexane (3:7) and evaporation of the solvent
under reduced pressure gave the pure products in 65–90%
yields. All the products gave satisfactory spectral data in
accordance with the assigned structures. Diethyl 1-acet-
oxyphenylmethylphosphonate (2a).15 Colorless oil; 1H
NMR (CDCl3/TMS—250 MHz): 1.13–1.32 (6H, m), 2.09
(3H, d, J = 2 Hz), 3.75–4.10 (4H, m), 6.06 (1H, d,
J = 13.5 Hz), 7.21–7.43 (5H, m). 31P NMR (CDCl3/
H3PO4—101.2 MHz):17.82 ppm; 13C NMR (CDCl3/
TMS—62.9 MHz):16.2 (d, JPC = 6.3 Hz), 16.3 (d,
JPC = 6.3 Hz), 20.8, 63.1–63.3, 67.6 (d, JPC = 169.8 Hz),
127.8 (d, JPC = 5.7 Hz), 128.4 (d, JPC = 2.5 Hz), 128.6 (d,
JPC = 2.5 Hz), 133.4 (d, JPC = 1.9 Hz), 169.3 (d,
JPC = 9.0 Hz). Diethyl 1-acetoxy(4-methoxyphenyl)methyl
phosphonate (2b).15 Colorless oil; 1H NMR (CDCl3/
TMS—250 MHz): 1.13–1.22 (6H, m), 2.09 (3H, d,
J = 1.2 Hz), 3.77 (3H, d, J = 1.5 Hz), 3.85–4.15 (4H, m),
6.05 (1H, d, J = 13.0 Hz), 6.86 (2H, d, J = 7.7 Hz), 7.41
(2H, d, J = 7.7 Hz). 31P NMR (CDCl3/H3PO4—
101.2 MHz):18.22 ppm; 13C NMR (CDCl3/TMS—
62.9 MHz):16.2 (d, JPC = 5.8 Hz), 16.4 (d, JPC = 5.7 Hz),
20.9, 55.2, 63.1–63.3, 70.0 (d, JPC = 172.7 Hz), 113.9 (d,
JPC = 1.8 Hz), 125.4 (d, JPC = 1.8 Hz), 129.5 (d,
JPC = 6.1 Hz), 159.9 (d, JPC = 2.5 Hz), 169.3 (d,
JPC = 9.1 Hz). Diethyl 1-acetoxy(4-methylphenyl)methyl
phosphonate (2c).15 Colorless oil; 1H NMR (CDCl3/
TMS—250 MHz): 1.15–1.30 (6H, m), 2.14 (3H, s), 2.32
(3H, s), 3.85–4.15 (4H, m), 6.09 (1H, d, J = 13.2 Hz), 7.16
(2H, d, J = 8.0 Hz), 7.38 (2H, d, J = 8.0 Hz). 31P NMR
JPC = 6.3 Hz), 20.8, 63.3–63.4, 69.8 (d, JPC = 170.6 Hz),
122.9 (d,JPC = 3.6 Hz), 129.5 (d, JPC = 5.8 Hz), 131.6 (d,
JPC = 2.1 Hz), 132.6 (d, JPC = 2.0 Hz), 169.2 (d,
JPC = 9.0 Hz). Anal. Calcd for C13H18BrO5P: C, 42.74;
H, 4.93. Found: C, 42.8; H, 5.1. Diethyl 1-acetoxy(3-
chlorophenyl)methyl phosphonate (2f).15 Colorless oil; 1H
NMR (CDCl3/TMS—250 MHz): 1.10–1.25 (6H, m), 2.10
(3H, s), 3.85–4.18 (4H, m), 6.05 (1H, d, J = 14.0 Hz), 7.15–
7.45 (4H, m). 31P NMR (CDCl3/H3PO4—101.2 MHz):
16.92 ppm; 13C NMR (CDCl3/TMS—62.9 MHz): 16.1 (d,
JPC = 5.6 Hz), 16.2 (d, JPC = 5.6 Hz), 20.6, 63.2 (d,
JPC = 6.3 Hz), 63.3 (d, JPC = 6.3 Hz), 69.8 (d,
JPC = 169.8 Hz), 125.9 (d, JPC = 5.6 Hz), 127.7 (d,
JPC = 5.7 Hz), 128.7 (d, JPC = 2.5 Hz), 129.6, 134.3,
135.6, 168.9 (d, JPC = 8.2 Hz). Diethyl 1-acetoxy(3-meth-
oxyphenyl)methyl phosphonate (2g).7b Colorless oil; 1H
NMR (CDCl3/TMS—250 MHz): 1.15–1.29 (6H, m), 2.14
(3H,s), 3.78 (3H, d, J = 1.5 Hz), 3.85–4.15 (4H, m), 6.07
(1H, d, J = 13.7 Hz), 6.78–7.28 (4H, m). 31P NMR
(CDCl3/H3PO4—101.2 MHz): 17.76 ppm; 13C NMR
(CDCl3/TMS—62.9 MHz): 16.2 (d, JPC = 5.8 Hz), 16.4
(d, JPC = 5.9 Hz), 20.9, 55.2, 63.3 (d, JPC = 5.9 Hz), 70.3
(d, JPC = 170.1 Hz), 113.1 (d, JPC = 5.5 Hz), 114.3 (d,
JPC = 2.7 Hz), 120.1 (d, JPC = 5.8 Hz), 129.5, 134.8, 159.5,
169.2 (d, JPC = 9.1 Hz). Diethyl 1-acetoxy(3-bromophe-
nyl)methyl phosphonate (2h). Colorless oil; 1H NMR
(CDCl3/TMS—250 MHz): 1.10–1.25 (6H, m), 2.10 (2H, d,
J = 2.2 Hz), 3.85–4.18 (4H, m), 6.03 (1H, d, J = 13.7 Hz),
7.10–7.58 (4H, m). 31P NMR (CDCl3/H3PO4—
101.2 MHz):17.03 ppm; 13C NMR (CDCl3/TMS—
62.9 MHz):16.1 (d, JPC = 5.7 Hz), 16.2 (d, JPC = 5.7 Hz),
20.6, 63.2 (d, JPC = 7.0 Hz), 63.3 (d, JPC = 7.0 Hz), 69.4 (d,
JPC = 169.8 Hz), 122.2 (d, JPC = 2.5 Hz), 126.3 (d,
JPC = 5.0 Hz), 129.8 (d, JPC = 1.9 Hz), 130.4 (d,
JPC = 5.7 Hz), 131.5 (d, JPC = 2.5 Hz), 135.6 (d,
JPC = 1.9 Hz), 168.8 (d, JPC = 8.8 Hz). Anal. Calcd for
C13H18BrO5P: C, 42.74; H, 4.93. Found:C, 42.6; H, 5.1.
Diethyl 1-acetoxy(3-methylphenyl)methyl phosphonate
(2i). Colorless oil; 1H NMR (CDCl3/TMS—250 MHz):
1.15–1.30 (6H, m), 2.16 (3H, s), 2.34 (3H, s), 3.85–4.15
(4H, m), 6.09 (1H, d, J = 13.2 Hz), 7.10–7.45 (4H, m). 31P
NMR
(CDCl3/H3PO4—101.2 MHz):18.00 ppm;
13C
NMR (CDCl3/TMS—62.9 MHz):16.2 (d, JPC = 5.9 Hz),
16.4 (d, JPC = 5.9 Hz), 20.9, 21.4, 63.1–63.3, 70.5 (d,
JPC = 170.1 Hz), 124.9 (d, JPC = 5.8 Hz), 128.3 (d,
JPC = 2.2 Hz), 128.5 (d, JPC = 5.9 Hz), 129.5 (d,
JPC = 2.8 Hz), 133.3, 138.1, 169.3 (d, JPC = 8.9 Hz). Anal.
Calcd for C14H21O5P: C, 56.00; H, 7.00. Found:C, 56.2;
H, 7.2. Diethyl 1-acetoxy(2-chlorophenyl)methyl phos-
phonate (2j).15 Colorless oil; 1H NMR (CDCl3/TMS—
250 MHz): 1.15 (3H, t, J = 7.0 Hz), 1.28 (3H, t,
J = 7.0 Hz), 2.12 (3H, s), 3.80–4.21 (4H, m), 6.58 (1H, d,
J = 13.8 Hz), 7.15–7.65 (4H, m). 31P NMR (CDCl3/
H3PO4—101.2 MHz):17.24 ppm; 13C NMR (CDCl3/
TMS—62.9 MHz):16.2 (d, JPC = 5.7 Hz), 16.3 (d,
JPC = 5.7 Hz), 20.7, 63.2 (d, JPC = 6.6 Hz), 66.8 (d,
JPC = 172.3 Hz), 127.0, 129.4, 129.6 (d, JPC = 3.8 Hz),
129.8 (d, JPC = 2.8 Hz), 131.9, 133.6 (d, JPC = 7.9 Hz),
168.9 (d, JPC = 9.6 Hz). Diethyl 1-acetoxy(2-methylphe-
nyl)methyl phosphonate (2k).7b Colorless oil; 1H NMR
(CDCl3/TMS—250 MHz): 1.10–1.35 (6H, m), 2.14 (3H, s),
2.48 (3H, s), 3.85–4.18 (4H, m), 6.36 (1H, d, J = 13.7 Hz),
7.10–7.65 (4H, m). 31P NMR (CDCl3/H3PO4—
101.2 MHz): 18.58 ppm; 13C NMR (CDCl3/TMS—
62.9 MHz): 16.2 (d, JPC = 5.6 Hz), 16.4 (d, JPC = 5.6 Hz),
19.6, 20.92, 63.2 (d, JPC = 6.9 Hz), 67.0 (d,
JPC = 171.7 Hz), 126.2, 128.1 (d, JPC = 4.4 Hz),
128.6130.3, 132.1, 136.7 (d, JPC = 7.5 Hz), 169.3 (d,
JPC = 10.0 Hz). Diethyl 1-acetoxy(1-naphthyl)methyl
(CDCl3/H3PO4—101.2 MHz):18.09 ppm;
13C
NMR
(CDCl3/TMS—62.9 MHz):16.2 (d, JPC = 5.8 Hz), 16.4 (d,
JPC = 5.7 Hz), 20.9, 21.2, 63.2 (d, JPC = 6.8 Hz), 70.3 (d,
JPC = 171.0 Hz), 127.9 (d, JPC = 6.0 Hz), 129.1 (d,
JPC = 2.1 Hz), 130.4 (d, JPC = 2.0 Hz), 138.6 (d,
JPC = 3.0 Hz), 169.3 (d, JPC = 9.0 Hz). Diethyl 1-acet-
oxy(4-chlorophenyl)methyl phosphonate (2d).15 Colorless
oil; 1H NMR (CDCl3/TMS—250 MHz): 1.13–1.30 (6 H,
m), 2.13 (3H, s), 3.85–4.18 (4H, m), 6.05 (1H, d,
J = 13.7 Hz), 7.30 (2H, d, J = 8.5 Hz), 7.39 (2H, d,
J = 8.5 Hz).
31P
NMR
(CDCl3/H3PO4—
101.2 MHz):17.20 ppm; 13C NMR (CDCl3/TMS—
62.9 MHz):16.2 (d, JPC = 6.3 Hz), 16.3 (d, JPC = 6.3 Hz),
20.6, 63.2–63.3, 69.8 (d, JPC = 171.1 Hz), 128.6 (d,
JPC = 1.9 Hz), 129.2 (d, JPC = 5.7 Hz), 132.2 (d,
JPC = 1.9 Hz), 134.6 (d, JPC = 3.1 Hz), 168.9 (d,
JPC = 8.8 Hz). Diethyl 1-acetoxy(4-bromophenyl)methyl
phosphonate (2e). Colorless oil; 1H NMR (CDCl3/
TMS—250 MHz): 1.15–1.30 (6H, m), 2.15 (3H, s), 3.80–
4.08 (4H, m), 6.03 (1H, d, J = 13.7 Hz), 7.33 (2H, d,
J = 8.2 Hz), 7.47 (2H, d, J = 8.2 Hz). 31P NMR (CDCl3/
H3PO4—101.2 MHz):17.15 ppm; 13C NMR (CDCl3/
TMS—62.9 MHz):16.3 (d, JPC = 6.3 Hz), 16.4 (d,

B. Kaboudin, M. Karimi / Bioorg. Med. Chem. Lett. 16 (2006) 5324–5327
5327
phosphonate (2l).15 Colorless oil; 1H NMR (CDCl3/
TMS—250 MHz): 0.95 (3H, t, J = 7.0 Hz), 1.15 (3H, t,
J = 7.0 Hz), 2.10 (3H, s), 3.58–4.21 (4H, m), 6.94 (1H, d,
J = 14.2 Hz), 7.35–8.0 (6H, m), 8.22 (1H, d, J = 8.5 Hz).
31P NMR (CDCl3/H3PO4—101.2 MHz): 18.13 ppm; 13C
NMR (CDCl3/TMS—62.9 MHz): 16.1 (d, JPC = 5.6 Hz),
16.3 (d, JPC = 5.6 Hz), 20.8, 63.2 (d, JPC = 6.6 Hz), 67.1 (d,
JPC = 172.0 Hz), 123.7, 125.2 (d, JPC = 3.8 Hz), 125.8,
126.5, 126.7 (d, JPC = 5.9 Hz), 128.6, 129.4, 129.7, 133.6
(d, JPC = 5.5 Hz), 133.6, 169.2 (d, JPC = 9.0 Hz). Diethyl
(d, JPC = 5.7 Hz), 16.3 (d, JPC = 5.7 Hz), 20.8, 63.2–63.3,
70.5 (d, JPC = 169.8 Hz), 125.2 (d, JPC = 4.4 Hz), 126.3,
126.5, 127.3 (d, JPC = 7.5 Hz), 127.6, 128.1, 128.2 (d,
JPC = 1.9 Hz), 130.9 (d, JPC = 2.5 Hz), 132.9 (d,
JPC = 2.5 Hz), 133.2 (d, JPC = 2.5 Hz), 169.2 (d,
JPC = 8.8 Hz). Diethyl 1-acetoxy(2-phenylethenyl)methyl
phosphonate (2j).15 Colorless oil; 1H NMR (CDCl3/
TMS—250 MHz): 1.15–1.35 (6H, m), 2.11 (3H, s), 3.95–
4.30 (4H, m), 5.80 (1H, ddd, J = 1.0, J = 7.2 and
J = 14.0 Hz), 6.10–6.25 (1H, m), 6.58 (1H, dd, J = 3.5
and J = 15.7 Hz), 7.15–7.45 (5H, m). 31P NMR (CDCl3/
H3PO4—101.2 MHz): 6.72 ppm; 13C NMR (CDCl3/
TMS—62.9 MHz): 16.2–16.3, 20.8, 63.1–63.4, 69.2 (d,
JPC = 171.4 Hz), 120.1 (d, JPC = 4.5 Hz) 126.7 (d,
JPC = 1.3 Hz), 128.6, 135.0, 135.6 (d, JPC = 2.8 Hz),
169.2 (d, JPC = 7.9 Hz).
1-acetoxy(2-naphthyl)methyl
phosphonate
(2l).15,7b
Colorless oil; 1H NMR (CDCl3/TMS—250 MHz): 1.10
(3H, t, J = 7.0 Hz), 1.17 (3H, t, J = 7.0 Hz), 2.10 (3H, s),
3.75–4.15 (4H, m), 6.28 (1H, d, J = 13.7 Hz), 7.30–7.95
(7H, m). 31P NMR (CDCl3/H3PO4—101.2 MHz):
17.82 ppm; 13C NMR (CDCl3/TMS—62.9 MHz): 16.2