(E) Enol ethers from the stereoselective reduction of α-alkoxy- β-ketophosphonates and Wittig type reaction

Article abstract of DOI:10.1007/s11426-010-4057-1

When α-alkoxy-β-ketophosphonates, prepared by the Rh(II) mediated insertion reaction of α-diazo-β-ketophosphonates into the OH bond of primary alcohols, were reduced either by NaBH₄ in the presence of CaCl₂ or by DIBAL, they respectively gave the corresponding anti or syn stereomeric hydroxyphosphonates with pronounced to complete stereoselectivity. Submitted to the action of potassium tert-butoxyde, syn isomers led to the corresponding pure (E) enol ethers in moderate to good yields. Under the same conditions anti isomers led to a mixture of (Z) and (E) enol ethers in rather poor yields. The sequence was applied to the preparation of some allyl-vinyl ethers with a (E) configuration for the vinylic double bond.

Full text of DOI:10.1007/s11426-010-4057-1

SCIENCE CHINA
Chemistry
September 2010 Vol.53 No.9: 1937–1945
doi: 10.1007/s11426-010-4057-1
• ARTICLES •
(E) Enol ethers from the stereoselective reduction of
-alkoxy--ketophosphonates and Wittig type reaction
DAYOUB Wissam1* & DOUTHEAU Alain2
1Laboratoire de Catalyse et Synthèse Organique, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS),
CNRS, UMR5246, Université Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne, France
2Institut National des Sciences Appliquées de Lyon, Laboratoire de Chimie Organique et Bioorganique,
ICBMS UMR 5246 CNRS Université Lyon 1 INSA Lyon, F 69622 Villeurbanne, France
Received April 25, 2010; accepted June 16, 2010
When -alkoxy--ketophosphonates, prepared by the Rh(II) mediated insertion reaction of -diazo--ketophosphonates into
the OH bond of primary alcohols, were reduced either by NaBH4 in the presence of CaCl2 or by DIBAL, they respectively
gave the corresponding anti or syn stereomeric hydroxyphosphonates with pronounced to complete stereoselectivity. Submit-
ted to the action of potassium tert-butoxyde, syn isomers led to the corresponding pure (E) enol ethers in moderate to good
yields. Under the same conditions anti isomers led to a mixture of (Z) and (E) enol ethers in rather poor yields. The sequence
was applied to the preparation of some allyl-vinyl ethers with a (E) configuration for the vinylic double bond.
-alkoxy--ketophosphonates, reduction, insertion, rhodiocarbenoids, Wittig-Wadsworth-Emmons, enol ethers
conducted on the Wadsworth-Emmons reaction with the
1 Introduction
anti and syn -alkoxy--hydroxyphosphonates. As part of
our continuing interest in the chemistry of -diazo--keto-
phosphonates [6], we have explored the use of these com-
pounds as starting materials for the stereoselective prepara-
tion of enol ethers and here we report our results.
The route that we envisaged for the synthesis of target
compounds is depicted in Scheme 1. The insertion reaction
of rhodio-carbenoids generated from -diazo--ketophos-
phonates 2 into the OH bond of alcohols would afford the
alkoxy-ketophosphonates 3. The stereoselective reduction
of compounds 3 would lead to either the hydroxy-phos-
phonates 4-anti or their stereoisomers 4-syn, which submit-
ted to the action of a base would respectively give the (Z) or
(E) enol ethers 5 [7].
O-alkyl enol ethers are significant intermediates in organic
synthesis, which are used in various cycloaddition reactions
and Claisen rearrangement [1]. However, stereoselective
methods for their preparation are relatively rare [2]. Several
years ago, Kluge et al. [3] and Warren et al. [4] simultane-
ously reported the preparation of some alkyl enol ethers by
performing a Wittig type reaction from -alkoxy--hydroxy
diethylphosphonates or diphenylphosphine oxides, respec-
tively. The latter compounds resulted from the condensation
of the appropriate anions on aldehydes or ketones and con-
sisted of a mixture of stereoisomers leading to a mixture of
(Z) and (E) enol ethers. However, it was shown by Warren
et al. that when the Wittig-Horner reaction was carried out
on pure anti or syn -hydroxy-diphenylphosphine oxides, it
respectively led to the corresponding pure (E) or (Z) enol
ethers [5]. To our knowledge the same study has not been
2 Experimental
2.1 General experimental
Solvents were distilled and dried before use: diethyl ether
*Corresponding author (email: wissam.dayoub@univ-lyon1.fr)
© Science China Press and Springer-Verlag Berlin Heidelberg 2010
chem.scichina.com
www.springerlink.com

1938
DAYOUB Wissam, et al. Sci China Chem September (2010) Vol.53 No.9
separated and the aqueous layer was extracted with ethyl
acetate (2 × 50 mL). The combined organic extracts were
dried. After solvent evaporation in vacuo the residue was
purified by chromatography (ethyl acetate/pentane: 10/3) to
give first (Rf = 0.94) 1g of unreacted starting ester, and then
(Rf = 0.44) 1a (4.74 g, 74%). IR: 1710. 1H NMR:  0.88 (t, J
= 6.4 Hz, 3H), 1.25 (m, 22H), 1.58 (quint, J = 6.7 Hz, 2H),
2.6 (t, J = 7.3 Hz, 2H), 3.08 (d, 2JH-P =22.7 Hz, 2H), 3.79 (d,
3JH-P =11.2 Hz, 6H). 13C NMR:  14.13, 22.72, 23.43, 28.97,
29.39, 29.41, 29.50, 29.64, 29.69, 29.71, 32.0, 41.25 (d,
3
1JC-P = 128.3 Hz), 44.3 (d, JC-P = 1.5 Hz), 53.0 (d, 2JC-P =6.5
2
Hz), 202.01 (d, JC-P = 6.3 Hz). Anal. calcd for C18H37O4P1:
C, 61.89; H, 10.60; found: C, 61.79; H, 10.68.
Scheme 1 Envisaged sequence for the stereoselective preparation of (Z) and
(E) enol ethers from alkoxy-ketophosphonates 3 (3 and 4 are racemic mixtures).
Dimethyl-(1-diazo-2-oxo-hexadecyl) phosphonate (2a)
To a dispersion of NaH (0.18 g, 4.54 mmol) (washed twice
with 30 mL of dry pentane) in THF (30 mL) at 0 °C was
added a solution of 1a (1.32 g, 3.8 mmol). The reaction
mixture was stirred for 10 min at room temperature, and
then a solution of tosylazide (Caution: tosylazide is highly
toxic and suspected of being explosive) [8] (0.97 g, 4.93
mmol) in THF (20 mL) was added and the stirring was pur-
sued for 30 min. Brine (20 mL) was added and the solvent
was evaporated in vacuo. The residue was extracted with
EtOAc (2 × 50 mL) and the organic layer was washed with
10% NaOH aq (20 mL), water (20 mL) and dried. After
solvent evaporation the crude diazo was chromatographed
(diethylether/pentane; 3/1) to give 1.35 g (95%) of pure 2a.
IR: 2120, 1650. 1H NMR:  0.88 (t, J=6.8 Hz, 3H), 1.25 (m,
from potassium hydroxide, pentane from phosphorus pen-
toxide, tetrahydrofuran from sodium benzophenone ketyl,
and pyridine from calcium hydride. Toluene was dried over
sodium. Organic solutions were dried over anhydrous so-
dium sulfate. The reactions were performed under a con-
stant flow of nitrogen. The reactions were monitored by TLC.
on Silica Gel 60 F254 (Merck) and detection was carried out
by charring with a 5% phosphomolybdic acid solution in
ethanol containing 10 % of H2SO4. Silica gel (Kieselgel 60,
70–230 mesh ASTM, Merck) was employed for column
chromatographies. Melting points were determined on a
Kofler block apparatus. IR spectra were recorded on a
Perkin-Elmer 1310 spectrometer and are expressed in cm1.
1H NMR and 13C NMR spectra were recorded with a Bruker
AC200 (200/50.32 and 300 MHz) spectrometer. All NMR
recordings were referenced to CHCl3 resonances (7.26 and
77.0 ppm). Chemical shifts are given in ppm. Coupling
constants are expressed in Hertz and splitting pattern abbre-
viations are as follows: s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; M, massif; p, pseudo. Multiplicity
(13C NMR) was determined by DEPT sequences. The HR
mass spectra were recorded with a ThermoFinnigan spec-
trometer. Elemental analyses were performed by “Service
Central de Microanalyses du CNRS” 69 Solaize (France).
22H), 1.63 (m, 2H), 2.53 (t, J = 7.5 Hz, 2H), 3.84 (d, 3JH-P
=
12 Hz, 6H). 13C NMR:  13.85, 22.34, 23.90 (10C), 31.22,
2
39.45, 53.52 (2d, JC-P = 5.6 Hz), 62.85 (d, 1JC-P =220.6 Hz),
192.75 (d, 2JC-P =13.0 Hz). Anal. calcd for C18H35N2O4P1: C,
57.56; H, 9.33. Found: C, 58.19; H, 9.82.
Dimethyl-(1-diazo-2-oxo-propyl)phosphonate (2b)
To a solution of commercially available dimethyl-(2-oxo-
propyl)phosphonate 1b (8.37 mmol) in acetonitrile (5 mL)
was added first tosylazide (2.14 g, 10.9 mmol) and then
potassium carbonate (1.62 g, 11.7 mmol). The reaction
mixture was stirred at room temperature for 2 h and then a
saturated aqueous ammonium chloride solution (15 mL)
was added. After extraction (EtOAc, 2 × 30 mL), the com-
bined organic layers were dried and the solvent was evapo-
rated in vacuo. The crude product was chromatographed
(EtOAc) to afford 1.56 g (97%) of 2c as a yellow oil. IR:
1650, 2120. 1H NMR:  2.27 (s, 3H), 3.82 (d, 3JH-P =12 Hz,
2.2 Synthesis of -diazo--ketophosphonates (2a) and (2b)
Dimethyl-(2-oxo-hexadecyl)phosphonate (1a)
To a solution of trimethylphosphonate (40 mmol) in 15 mL
of anhydrous THF cooled at 60 °C was added 14.6 mL of
a 2.5 M solution of n-butyllithium in hexanes (36.5 mmol).
The reaction mixture was allowed to warm to 30 °C and
stirred at this temperature for 15 m before the addition of a
solution of 4.7 g (18.3 mmol) methyl pentadecanoate in
pentane (40 mL). At the end of the addition the reaction
mixture was stirred for 2 h at room temperature and then
hydrolyzed with saturated aqueous ammonium chloride
solution (20 mL) and water (10 mL). The organic layer was
6H). 13C NMR:  27.15 (d, 4JC-P = 1.0 Hz), 53.64 (d, 2JC-P
=
5.5 Hz), 63.49 (d, 1JC-P =220.2 Hz), 189.8 (d, 2JC-P =13.0 Hz).
2.3 Preparation of -alkoxy--ketophosphonates (3a–k)
and allylic esters (6f–h)
To a solution of alcohol (5.34 mmol) in dry toluene (20 mL)
was added a catalytic amount of Rh2(OAc)4 (0.1 mol%) at

DAYOUB Wissam, et al. Sci China Chem September (2010) Vol.53 No.9
1939
3
80 °C and then, over 10 min, a solution of diazo 2a or 2b
(2.67 mmol) in 10 mL of toluene. The reaction mixture was
maintained at 80 °C for an additional hour. The solvent was
evaporated in vacuo and the crude product was chroma-
tographed.
2H), 2.26 (s, 3H), 1.96 (m, 2H), 3.78 (2d, JH-P = 10.8 Hz,
1
6H), 4.16 (m, J = 6.4 Hz, 2H), 4.25 (d, JH-P =19.9 Hz, 1H),
5.56 (m, Jcis = 11.0 Hz, 2H). 13C NMR:  13.62, 22.55,
2
2
29.49, 27.36, 53.96 (d, JC-P = 6.8 Hz), 54.02 (d, JC-P = 6.8
1
Hz), 67.82, 81.72 (d, JC-P = 151.0 Hz), 124.11, 136.16,
204.17. HRMS (FAB) [M+] calcd for C11H21O5P1: 264.1126;
found: 264.1124.
Dimethyl-1-(benzyloxy)-2-oxo-hexadecylphosphonate (3a)
Chromatography (Et2O/pentane; 2/1). Yield: 77% as green
1
Dimethyl-1-(1-methylprop-2-enyloxy)-2-oxo-propylphosph-
oil. IR (CCl4): 1715. H NMR:  0.88 (t, J = 6.7 Hz, 3H),
onate (3f)
1.25 (m, 22H), 1.67 (m, 2H), 2.62 (d x sext, J=17.8 Hz, J=
2
1
7.3 Hz, 2H), 3.80 (d, JH-P = 10.9 Hz, 6H), 4.35 (d, JH-P
=
Chromatography (EtOAc). Yield: 21% as a green oil (mix-
ture of diastereoisomers 55/45). IR (CCl4): 1720. Major
3
19.6 Hz, 1H), 4.78 (d, JH-P = 11.9 Hz, 2H), 7.35 (s, 5H
arom). 13C NMR:  14.14, 22.71, 39.86, 53.94 (d, JC-P =6.8
2
1
isomer (55%) H NMR:  1.34 (d, J = 6.3 Hz, 3H), 2.31 (s,
Hz), 54.06 (d, 2JC-P =6.7 Hz), 74.3 (d, JC-P =10.0 Hz), 81.41
3H), 3.83 (2d, 2JH-P =10.8 Hz, 6H), 4.12 (m, J=8.0 Hz, 1H),
2
1
(d, 1JC-P =150.3 Hz), 128.42, 128.47, 128.64, 136.19, 205.8.
4.41 (d, JH-P = 21.9 Hz, 1H), 5.00–5.40 (m, 2H), 5.79–6.00
2
(m, 1H). 13C NMR: 21.36, 27.45, 54.15 (d, JC-P = 6.4 Hz),
Dimethyl-1-(diisopropylideneglycerol)-2-oxo-hexadecylphosp-
1
79.06, 80.02 (d, JC-P = 151.7 Hz), 118.85, 137.81, 204.59.
Minor isomer (45%) H NMR:  1.42 (d, J = 6.4 Hz, 3H),
2.26 (s, 3H), 3.75 (q, J = 8.0 Hz, 1H), 3.83 (2d, JH-P =10.8
ho-nate (3b)
1
1
2
IR (CCl4): 1715. H NMR:  0.86 (t, J = 3.0 Hz, 3H), 1.23
(m, 30H), 2.7 (t, J = 7.0 Hz, 2H), 3.83 (d, 3J=11.0 Hz, 6H),
3.50–4.40 (m, 7H), 4.50 (d, JH-P = 20.0 Hz, 1H). 13C NMR: 
14.15, 22.73, 25.33, 25.71, 26.77, 29.56, 31.97, 33.09,
1
Hz, 6H), 4.27 (d, JH-P = 19.3 Hz, 1H), 5.00–5.40 (m, 2H),
5.5–5.78 (m, 1H). 13C NMR:  21.36; 27.45, 53.87 (d, JC-P
2
1
2
2
= 6.4 Hz), 79.29, 81.32 (d, JC-P = 97.9 Hz), 118.71, 138.38,
53.70 (d, JC-P = 6.9 Hz), 54.38 (d, JC-P = 6.9 Hz), 66.35,
204.43. HRMS (FAB) [(M+H)+] calcd for C9H17O5P1:
237.0892; found: 237.0894.
2
2
70.81 (d, JC-P = 5.2 Hz), 70.91 (d, JC-P = 5.3 Hz), 73.49 (d,
JC-P = 2.63 Hz), 74.55, 74.97 (d, JC-P = 2.32 Hz), 78.28 (d,
1JC-P = 159.8 Hz), 83.54 (d, JC-P = 150.2 Hz), 109.66. Anal.
1
2-Dimethylphosphonate-1-methylprop-2-enyl propanoate (6f)
calcd for C24H45O7P1: C 60.12, H 9.81, P 6.68, O 23.38;
found: C 60.53, H 9.88.
1
Yield: 17% as green oil. IR (CCl4): 1735. H NMR:  1.34
(d, J=6.5 Hz, 3H), 1.46 (dd, 2JH-P =18.4 Hz, J=6.6 Hz, 3H),
1
Dimethyl-1-(benzyloxy)-2-oxo-propylphosphonate (3c)
3.1 (qd, JH-P = 23.4 Hz, J = 7.3 Hz, 1H), 3.78 (m, 1H), 3.78
3
1
3
(2d, JH-P = 10.8 Hz, 6H), 5.14–5.43 (m, 2H), 5.76–5.94 (m,
1H). HRMS (FAB) [(M+H)+] calcd for C9H17O5P1:
237.0892; found: 237.0894.
IR (CCl4): 1715. H NMR:  2.29 (s, 3H), 3.81 (d, JH-P
=
11.0 Hz, 3H), 3.80 (d, J=11.0 Hz, 3H), 4.33 (d, J=20.0 Hz,
1H), 4.64 and 4.74 (AB, J = 12.0 Hz, 2H), 7.35 (s, 5H
2
arom.). 13C NMR:  27.47, 54.00 (d, JC-P = 6.8 Hz), 54.04
2
1
(d, 2JC-P = 6.8 Hz), 74.35 (d, JC-P = 10.0 Hz), 81.73 (d, JC-P
= 150.0 Hz), 128.37, 128.48, 128.64, 136.1, 203.75. Anal.
calcd for C12H17O5P1: C, 52.75; H, 6.23; found: C, 52.40; H,
6.12.
Dimethyl-1-(1-ethylprop-2-enyloxy)-2-oxo-propylphosphonate
(3g)
Chromatography (EtOAc). Yield: 19% as green oil (mix-
ture of diastereoisomers 55/45). IR (CCl4): 1720. Major
isomer (55%). 1H NMR:  0.91 (t, J = 7.4 Hz, 3H), 1.65 (m,
3
Dimethyl-1-(trans-hex-2-enyloxy)-2-oxo-propylphosphonate
(3d)
2H), 2.29 (s, 3H), 3.77 (m, 1H), 3.79 (d, JH-P = 10.8 Hz,
1
6H), 4.44 (d, JH-P = 21.9 Hz, 1H), 5.04–5.34 (m, 2H),
5.75–5.80 (m, 1H). 13C NMR:  9.63, 27.55, 28.25, 54.15
(d, JC-P =7.0 Hz), 78.31, 82.53 (d, JC-P =153.8 Hz), 120.22,
Chromatography (EtOAc). Yield: 81% as green oil. IR
1
2
1
(CCl4): 1720. H NMR:  0.82 (t, J = 7.4 Hz, 3H), 1.32 (m,
3
2
1
2H), 1.95 (m, 2H), 2.24 (s, 3H), 3.76 (2d, JH-P = 10.8 Hz,
136.49, 204.53 (d, J = 5.7 Hz). Minor isomer H NMR: 
0.91 (t, J = 7.4 Hz, 3H), 1.65 (m, 2H), 2.29 (s, 3H), 3.77 (m,
1
6H), 4.02 (m, J = 6.6 Hz, 2H), 4.26 (d, JH-P =20.2 Hz, 1H),
3
1
5.55 (m, Jtrans = 15.3 Hz, Jcis = 6.5 Hz, 2H). 13C NMR: 
1H), 3.79 (d, JH-P = 10.8 Hz, 6H), 4.44 (d, JH-P = 21.9 Hz,
1H), 5.04–5.34 (m, 2H), 5.75–5.80 (m, 1H). 13C NMR: 9.53,
27.71, 27.96, 53.71 (d, 2JC-P = 7.0 Hz), 77.36, 82.53 (d, 1JC-P
2
13.54. 21.96, 27.39, 34.21, 53.95 (d, JC-P = 6.8 Hz), 53.90
2
1
(d, JC-P =6.8 Hz), 73.28, 81.27 (d, JC-P =151.0 Hz), 124.53,
137.57, 204.17. HRMS (FAB) [M+] calcd for C11H21O5P1:
264.1126; found: 264.1127.
2
= 96.2 Hz), 119.97, 137.12, 204.49 (d, JC-P = 4.9 Hz).
HRMS (FAB) [(M+H)+] calcd for C10H19O5P: 251.1048;
found: 251.1047.
Dimethyl-1-(cis-hex-2-enyloxy)-2-oxo-propylphosphonate (3e)
2-Dimethylphosphonate-1-ethylprop-2-enyl propanoate (6g)
Chromatography (EtOAc). Yield: 83% as green oil. IR
(CCl4): 1720. H NMR:  0.83 (t, J = 7.4 Hz, 3H), 1.33 (m,
1
1
Yield: 18% as green oil. IR (CCl4): 1735. H NMR:  1.34

1940
DAYOUB Wissam, et al. Sci China Chem September (2010) Vol.53 No.9
3
(t, J = 7.3 Hz, 3H), 1.45 (dd, JH-P = 18.3, J = 7.3 Hz, 3H),
2.4 Reduction of 3a-c by NaBH4/CaCl2
1.76 (q, J=7.2 Hz, 2H), 3.07 (qd, 1JH-P =23.4 Hz, J=7.3 Hz,
To a solution of 3a–c (0.22 mmol) in dry MeOH (5 mL) at
10 °C was added CaCl2 (0.22 mmol). The reaction mixture
was stirred for 10 min and NaBH4 (0.24 mmol) was added.
The stirring continued for an extra 1.5 h at 10 °C. Then the
reaction mixture was allowed to warm at 0 °C and acetic
acid was added dropwise (pH 4) and the stirring was con-
tinued for an additional 15 min. Then NaHCO3 10% aq was
added (pH 7). After partial evaporation, the solvent was
extracted with diethyl ether (2 × 10 mL). The combined
organic layers were dried and concentrated in vacuo.
1H), 3.78 (2d, 2JH-P = 10.8 Hz, 6H), 3.86 (m, 1H), 5.15–5.47
(m, 2H), 5.68–5.85 (m, 1H). 13C NMR (mixture of diastereoi-
somers 55/45). Major isomer:  9.25, 11.63 (d, J = 1.9 Hz),
1
27.15, 39.07 (d, JH-P = 33.9 Hz), 53.23, 77.40, 117.23,
135.81, 168.85. Minor isomer:  9.31, 11.69 (d, J=1.9 Hz),
27.15, 39.02 (d, J = 33.9 Hz), 53.35, 77.31, 117.18, 135.68,
168.95. HRMS (FAB) [(M+H)+] calcd for C10H19O5P:
251.1048; found: 251.1049.
Dimethyl-1-(2,2-methylprop-2-enyloxy)-2-oxo-propylphosph-
onate (3h)
Dimethyl-1-(benzyloxy)-2-hydroxy-hexadecaylphosphonate
(4a)
Chromatography (EtOAc). Yield: 6% as green oil. 1H NMR:
3
 1.27 (s, 3H), 1.35 (s, 3H), 2.31 (s, 3H), 3.83 (2d, JH-P
=
Yield: 86%. (mixture of diastereoisomers. anti/syn : 90/10).
1
1
10.8 Hz, 6H), 4.32 (d, JH-P = 22.3 Hz, 1H), 5.19 (m, 2H),
Major isomer (4a-anti) H NMR:  0.88 (t, J = 6.4 Hz, 3H),
3
1.25 (m, 24H), 1.35–1.7 (m, 3H), 2.67 (s, 1H, OH), 3.68 (q,
5.80 (dd, Jtrans = 17.6 Hz, Jcis = 10.3 Hz, 1H). HRMS (FAB)
J = 3.5 Hz, 1H), 3.81 (d, 3JH-P =10.6 Hz, 3H), 3.85 (d, 3JH-P
=
[(M +H)+] calcd for C10H19O5P1 251.1048; found: 251.1041.
10.6 Hz, 3H), 4.60 and 4.88 (AB, J = 11.3 Hz, 2H), 7.32 (s,
5H arom.). 13C NMR:  13.93, 22.51, 25.56, 29.18–29.51,
31.75, 33.29 (d, J = 9.0 Hz), 52.78 (d, J = 7.0 Hz), 52.91 (d,
J = 7.0 Hz), 70.47 (d, J = 2.7 Hz), 74.40 (d, J = 2.3 Hz),
2-Dimethylphosphonate-2,2-dimethylprop-2-enyl propanoate
(6h)
1
Yield: 27% as green oil. IR (CCl4): 1735. H NMR:  1.46
1
2
76.87 (d, JC-P = 160.0 Hz), 128.06, 128.29, 128.42, 136.76.
(dd, JH-P = 18.1 Hz, J = 7.3 Hz, 3H), 1.63 (s, 6H), 3.1 (qd,
1
Minor isomer (4a-syn) H NMR:  0.88 (t, J = 6.4 Hz, 3H),
1JH P = 22.5 Hz, J = 7.3 Hz, 1H), 3.78 (2d, JH-P = 10.9 Hz,
3
-
1.25 (m, 24H), 1.41 (m, 2H), 1.72 (m, 1H), 3.09 (s, 1H, OH),
6H), 5.07–5.26 (m, 2H), 6.07 (dd, Jtrans =17.4 Hz, Jcis =10.1
3
3.63 (dd, JH-P = 6.9 Hz, J = 5.0 Hz, 1H), 3.79 (d, JH-P =12.5
1
Hz, 1H). 13C NMR:  11.55, 26.26, 26.31, 39.60 (d, JC-P
=
Hz, 3H), 3.84 (d, J = 12.3 Hz, 3H), 4.59 and 4.80 (AB, J =
11.3 Hz, 2H), 7.30 (s, 5H arom.). 13C NMR:  13.95, 22.52,
25.22, 29.19–29.52, 31.76, 32.59 (d, J = 8.0 Hz), 52.93 (d,
133.0 Hz), 53.23 (d, J = 6.4 Hz), 82.17, 113.11, 141.98,
168.22. HRMS (FAB) [(M+H)+] calcd for C10H19O5P1:
251.1048; found: 251.10413.
2
2JC-P = 7.0 Hz), 53.07 (d, JC-P = 7.0 Hz), 70.82 (d, J = 2.7
Hz), 74.40 (d, J = 3.3 Hz), 78.22 (d, 1JC-P =157.0 Hz), 128.0,
128.19, 128.31, 136.85. Anal. calc for C25H45O5P: C, 65.64;
H, 9.85; found: C, 65.41; H, 9.54. (mixture of 4a-syn and
4a-anti).
Dimethyl-1-(prop-2-enyloxy)-2-oxo-hexadecylphosphonate (3i)
Chromatography (Et2O). Yield: 62% as green oil. IR (CCl4):
1715. 1H NMR:  0.88 (t, 3H), 1.25 (s, 22H), 1.58 (m, 2H),
2.64 (m, 2H), 2.64 (m, 2H), 3.80 (qt, J = 22.0 Hz, J = 12.0
Hz, 2H), 3.83 (2d, 3JH-P = 10.8 Hz, 6H), 4.35 (d, J=19.8 Hz,
Dimethyl-1-(diisopropylideneglycerol)-2-hydroxy-hexadecyl-
phosphonate (4b)
1H), 5.31 (m, 2H), 5.91 (ddt, Jtrans = 17.7 Hz, Jcis =10.2 Hz,
J = 5.8 Hz, 2H). 13C NMR:  4.09, 22.09, 22.67, 23.127,
Yield: 78%. (mixture of diastereoisomers. anti/syn: 95/5).
Major isomer (4b-anti) mp 59 °C. IR (CCl4): 3410. H
NMR:  0.88 (t, J = 6.4 Hz, 3H), 1.25 (s, 24H), 1.35 (s, 3H),
1
2
29.40, 31.91, 39.77, 53.91 (d, JC-P = 6.8 Hz), 53.98 (d, 2JC-P
= 6.8 Hz), 73.46, 81.54 (d, 1JC-P =150.7 Hz), 119.34, 132.98,
205.96. HRMS (FAB) [(M+H)+] calcd for C21H41O5P1:
405.2769; found: 405.2769.
1.43 (s, 3H), 1.58 (m, 2H), 3.05 (m, OH), 3.58 (m, 2H),
3
3
3.79 (d, JH-P = 10.6 Hz, 3H), 3.82 (d, JH-P = 10.6 Hz, 3H),
3.74–3.89 (m, H+2H), 4.06 (q, JH-P = 8.4 Hz, 1H), 4.30 (dt,
J =4.1 Hz, J =5.7 Hz, 1H). 13C NMR: 14.15, 22.73, 25.33,
Dimethyl-1-(hex-2-enyloxy)-2-oxo-hexadecylphosphonate (3j)
Chromatography (Et2O). Yield: 71% as a green oil. IR
(CCl4): 1720. 1H NMR:  0.86 (m, 6H), 1.41 (m, 26H), 2.01
2
25.71, 26.77, 29.56, 31.97, 33.09, 53.30 (d, JC-P = 6.9 Hz),
2
2
53.98 (d, JC-P = 6.9 Hz), 66.35, 70.81 (d, JC-P = 5.2 Hz),
3
2
(m, 2H), 2.64 (m, 2H), 3.80 (2d, JH-P = 10.8 Hz, 6H), 4.32
70.91 (d, JC-P = 5.3 Hz), 73.49 (d, JC-P = 2.63 Hz), 74.55,
1
(d, 1JH-P = 20.0 Hz, 1H), 4.65 (m, 2H), 5.62 (ddt, Jtrans =15.5
74.97 (d, JC-P = 2.32 Hz), 78.28 (d, JC-P = 159.8 Hz), 81.45
1
Hz, Jcis =10.3 Hz, J=6.5 Hz, 2H), 13C NMR:  13.66, 14.13,
(d, JC-P = 159.9 Hz), 109.66. Minor isomer (4b-syn). IR
1
2
(CCl4): 3440. H NMR:  0.88 (t, J = 6.4 Hz, 3H), 1.25 (s,
22.09, 22.71, 23.127, 29.4, 34.34, 39.85, 53.87 (d, JC-P
=
=
2
1
24H), 1.35 (s, 3H), 1.43 (s, 3H), 1.50 (m, 2H), 3.18 (m, OH),
3.58 (m, 2H), 3.79 (d, JH-P = 10.6 Hz, 3H), 3.82 (d, JH-P
6.8 Hz), 54.01 (d, JC-P = 6.8 Hz), 73.33, 80.94 (d, JC-P
3
3
150.8 Hz), 124.69, 137.58, 206.34. HRMS (FAB) [(M+H)+]
calcd for C24H47O5P1: 447.3239; found, 447.3239.
=
10.6 Hz, 3H), 3.74–3.89 (m, 9H), 4.06 (q, JH-P =8.4 Hz, 1H),

DAYOUB Wissam, et al. Sci China Chem September (2010) Vol.53 No.9
1941
4.30 (dt, J = 4.1 Hz, J = 5.7 Hz, 1H). 13C NMR:  14.13,
Dimethyl-1-(diisopropylideneglycerol)-2-hydroxy-hexadecyl-
phosphonate (4b-syn)
Yield: 65%. IR: 910, 1370, 3440. 1H NMR:  0.88 (t, J=6.4
22.71, 25.30, 25.58, 26.75, 29.51, 31.96, 33.01, 53.33 (d,
2
2JC-P = 6.9 Hz), 53.57 (d, JC-P = 6.9 Hz), 66.49, 70.93 (d,
2
2JC-P = 4.1 Hz), 70.91 (d, JC-P = 3.4 Hz), 73.49 (d, JC-P =3.4
Hz, 3H), 1.25 (s, 24H), 1.35 (s, 3H), 1.43 (s, 3H), 1.50 (m,
1
3
Hz), 74.57, 74.48 (d, JC-P = 3.3 Hz), 79.00 (d, JC-P = 158.9
2H), 3.18 (m, OH), 3.58 (m, 2H), 3.79 (d, JH-P = 10.6 Hz,
1
Hz), 82.14 (d, JC-P = 158.2 Hz), 109.57. Anal. calcd for
3
3H), 3.82 (d, JH-P = 10.6 Hz, 3H), 3.74-3.89 (m, 9H), 4.06
C24H47O7P1 : C 59.87, H 10.19; found: C, 59.76; H 10.09.
(q, JH-P = 8.4 Hz, 1H), 4.30 (dt, J = 4.1 Hz, J =5.7 Hz, 1H).
13C NMR:  14.13, 22.71, 25.30, 25.58, 26.75, 29.51, 31.96,
Dimethyl-1-(benzyloxy)-2-hydroxy-propylphosphonate (4c)
Yield: 97% (anti/syn : 65/35). Major isomer (4c-anti) IR:
2
2
33.01, 53.33 (d, JC-P = 6.9 Hz), 53.57 (d, JC-P = 6.9 Hz),
2
2
1
66.49, 70.93 (d, JC-P = 4.1 Hz), 70.91 (d, JC-P = 3.4 Hz),
73.49 (d, JC-P = 3.4 Hz), 74.57, 74.48 (d, JC-P = 3.3 Hz),
3400. H NMR:  1.25 (dd, J=6.4 Hz, J=0.3 Hz, 3H), 3.02
(s, 1H; OH), 3.60 (dd, J = 6.1 Hz, J = 4.7 Hz, 1H), 3.78 (d,
J = 7.8 Hz, 3H), 3.83 (d, J = 7.8 Hz, 3H), 4.07 (m, 1H), 4.60
(ABX, J = 11.3 Hz, J =1.3 Hz, 1H), 4.88 (AB, 1H), 7.36 (m,
5H arom). 13C NMR:  19.40 (d, J = 7.6 Hz), 53.01 (d, 2JC-P
1
1
79.00 (d, JC-P = 158.9 Hz), 82.14 (d, JC-P = 158.2 Hz),
109.57. Anal. calcd for C24H47O7P1: C 59.87, H 10.19;
found: C, 59.76; H 10.09.
2
= 6.8 Hz), 53.15 (d, JC-P = 6.8 Hz), 66.80 (d, J = 4.5 Hz),
Dimethyl-1-(benzyloxy)-2-hydroxy-propylphosphonate (4c-syn)
1
74.84 (d, J = 2.5 Hz), 78.76 (d, JC-P = 160.0 Hz), 128.27,
Yield: 50%. IR (CCl4): 3400. 1H NMR:  1.30 (d, J=6.4 Hz,
3H), 3.49 (s, 1H; OH), 3.63 (dd, J=6.4 Hz, J=5.8 Hz, 1H),
3.77 (d, J = 11.0 Hz, 3H), 3.82 (d, J =11.0 Hz, 3H), 4.10 (m,
1H), 4.62 (ABX, J = 11.3 Hz, J = 1.1 Hz, 1H), 4.81 (AB,
1H), 7.34 (m, 5H arom).13C NMR:  19.31 (d, J = 8.8 Hz),
128.50, 128.52, 136.95. Anal. calcd for C12H19O5P1: C,
52.36; H, 6.91; found: C, 52.37; H, 6.99. Minor isomer
1
(4c-syn): IR (CCl4): 3400. H NMR:  1.30 (d, J = 6.4 Hz,
3H), 3.49 (s, 1H; OH), 3.63 (dd, J=6.4 Hz, J=5.8 Hz, 1H),
3.77 (d, J = 11.0 Hz, 3H), 3.82 (d, J =11.0 Hz, 3H), 4.10 (m,
1H), 4.62 (ABX, J = 11.3 Hz, J = 1.1 Hz, 1H), 4.81 (AB,
1H), 7.34 (m, 5H arom.).13C NMR: 19.31 (d, J = 8.8 Hz),
2
2
52.80 (d, JC-P = 6.8 Hz), 53.60 (d, JC-P = 6.8 Hz), 67.30 (d,
1
J=4.5 Hz), 74.71 (d, J=2.5 Hz), 74.18 (d, JC-P =157.0 Hz),
2
2
128.19, 128.34, 128.49, 137.04. Anal. calcd for C12H19O5P1:
C, 52.36; H, 6.91; found: C, 52.56; H, 7.03.
52.80 (d, JC-P = 6.8 Hz), 53.60 (d, JC-P = 6.8 Hz), 67.30 (d,
J = 4.5 Hz), 74.71 (d, J = 2.5 Hz), 74.18 (d, 1JC-P =157.0 Hz),
128.19, 128.34, 128.49, 137.04. Anal. calcd for C12H19O5P1:
C, 52.36; H, 6.91; found: C, 52.56; H, 7.03.
Dimethyl-1-(trans-hex-2-enyloxy)-2-hydroxy-propylphosph-
onate (4d-syn)
1
3
Yield: 87%. IR (CCl4): 3380. H NMR:  0.89 (t, J = 7.3
2.5 Reduction of 3a-e and 3i–j by DiBAL
Hz, 3H), 1.28 (m, 3H), 1.44 (m, 2H), 2.03 (m, 2H), 3.81 (2d,
1
3JH-P = 10.4 Hz, 6H), 4.12 (m, 2H), 4.14 (d, JH-P = 20.2 Hz,
To a solution of ethers 3a–e and 3i–j (1 mmol) in anhydrous
THF (35 mL) at 78 °C was added a solution of DiBAL
1.6M in toluene (2 mL, 3.2 mmol). 3 h later, the reaction
mixture was allowed to warm to 30 °C and was acidified
to pH 3 with HCl 3 N (2 mL). The stirring was continued
for 45 min at 0 °C before NaHCO3 10% was added (pH 7).
The aqueous layer was extracted with diethyl ether (3 × 30
mL), and the organic layers were combined, dried over
MgSO4 and concentrated in vacuo. The crude product was
then purified by chromatography on silica gel (Et2O 100%)
to afford -hydroxyphosphonates 4a–e and 4i–j.
1H), 5.55 (m, 2H). 13C NMR:  13.66, 19.35, 34.32, 53.95,
2
2
(d, JC-P = 6.9 Hz), 53.90 (d, JC-P = 6.9 Hz), 67.28, 78.32 (d,
1JC-P = 157.4 Hz), 125.48, 136.41. HRMS (FAB) [(M+H)+]:
calcd for C11H23O5P1 : 267.1361; found: 267.1359.
Dimethyl-1-(cis-hex-2-enyloxy)-2-hydroxy-propylphosphonate
(4e-syn)
Yield: 66%. IR (CCl4): 3380. 1H NMR:  0.83 (t, J=7.3 Hz,
3H), 1.31 (m, 5H), 2.03 (m, 2H), 3.28 (s, 1H), 3.80 (2d,
1
3JH-P = 10.8 Hz, 7H), 4.13 (d, JH-P = 22.2 Hz, 1H), 4.14 (m,
2H), 5.56 (m, 2H). 13C NMR:  13.66, 19.35, 21.04, 25.03,
2
2
Dimethyl-1-(benzyloxy)-2-hydroxy-hexadecaylphosphonate
53.96 (d, JC-P = 6.9 Hz), 53.28 (d, JC-P = 6.9 Hz), 68.16,
1
(4a-syn)
68.19, 78.91 (d, JC-P = 157.2 Hz), 124.07, 134.91. HRMS
(FAB) [(M+H)+] calcd for C11H23O5P1: 267.1361; found:
267.1361.
1
Yield: 88%. H NMR:  0.88 (t, J = 6.4 Hz, 3H), 1.25 (m,
24H), 1.41 (m, 2H), 1.72 (m, 1H), 3.09 (s, 1H, OH), 3.63
(dd, JH-P = 6.9 Hz, J=5.0 Hz, 1H), 3.79 (d, J=12.5 Hz, 3H),
Dimethyl-1-(prop-2-enyloxy)-2-hydroxy-hexadecylphosph-
3.84 (d, J = 12.3 Hz, 3H), 4.59 and 4.80 (AB, J = 11.3 Hz,
2H), 7.30 (s, 5H arom). 13C NMR:  13.95, 22.52, 25.22,
29.19–29.52, 31.76, 32.59 (d, J = 8 Hz), 52.93 (d, 2JC-P =7.0
onate (4i)
1
Yield: 70%. IR : 3400. H NMR:  0.87 (t, 3H), 1.25 (s,
2
22H), 1.50 (m, 2H), 1.73 (m, 2H), 3.12 (m, OH), 3.56 (q, J
Hz), 53.07 (d, JC-P = 7.0 Hz), 70.82 (d, J = 2.73 Hz), 74.40
3
1
= 5.6 Hz, J = 6.8 Hz, 1H), 3.83 (2d, JH-P = 10.6 Hz, 6H),
(d, J = 3.3 Hz), 78.22 (d, JC-P = 157.0 Hz), 128.0, 128.19,
4.08 (m, 1H), 4.25 (q large, 1H), 5.26 (m, 2H), 5.90 (ddt, J =
128.31, 136.85.

1942
DAYOUB Wissam, et al. Sci China Chem September (2010) Vol.53 No.9
17.1 Hz, J = 10.3 Hz, J = 5.8 Hz, 2H). 13C NMR:  14.08,
3.71 (q, J = 5.9 Hz, J =10.7 Hz, 1H), 3.81 (q, J=4.8 Hz, J=
10.9 Hz, 1H), 3.83 (dd, J=6.1 Hz, J=8.5 Hz, 1H), 4.07 (dd,
J = 6.3 Hz, J = 8.4 Hz, 1H), 4.27 (m, 1H), 4.36 (dt, J = 6.3
Hz, J = 7.3 Hz, 1H), 5.94 (d, J = 6.3 Hz, 1H). 13C NMR: 
14.14, 22.73, 23.94, 25.39, 25.48, 26.70, 29.32, 29.40,
29.60, 29.70, 31.96, 66.62, 69.65, 74.48, 107.89, 144.80.
Anal. calcd for C22H42O3: C, 74.52; H, 11.94; found: C,
74.36; H, 11.76.
22.66, 25.53, 29.34, 29.61, 29.67, 31.91, 33.05, 53.91 (d,
2
2JC-P = 6.9 Hz), 53.98 (d, JC-P = 6.9 Hz), 70.91, 73.61, 78.43
(d, 1JC-P =157.7 Hz), 118.24, 133.82. HRMS (FAB) [(M+H)+]
calcd for C21H43O5P1: 407.2927; found: 407.2926.
Dimethyl-1-(hex-2-enyloxy)-2-hydroxy-hexadecylphosphonate
(4j)
1
Yield: 80%. IR (CCl4): 3400. H NMR:  0.86 (m, 6H),
Propenyloxymethyl-benzene (5c-E)
1.41 (m, 26H), 2.01 (q, J = 6.9 Hz), 3.26 (s, 1H), 3.78 (2d,
1
1
3JH-P = 10.4 Hz, 7H), 4.15 (d, JH-P = 20.0 Hz, 1H), 4.07 (m,
Yield: 45%. H NMR:  1.55 (dd, J = 6.6 Hz, J = 1.4 Hz,
2H), 5.59 (qt, J = 15.3 Hz, J = 6.5 Hz, 2H). 13C NMR: 
3H), 4.89 (dq, J = 13.0 Hz, J=6.5 Hz, 1H), 4.70 (s, 2H), 6.3
(dd, J = 12.5 Hz, J = 1.4 Hz, 1H), 7.34 (m, 5H arom.). Anal.
calcd for C10H12O: C, 81.04; H, 8.16; found: C, 79.90; H, 7.98.
13.67, 14.12, 22.13, 22.69, 29.64, 29.71, 31.94, 34.34,
2
2
53.08 (d, JC-P = 7.0 Hz), 53.22 (d, JC-P = 7.0 Hz), 70.44,
1
73.36, 77.59 (d, JC-P = 157.0 Hz), 125.47, 136.39. HRMS
Propenyloxymethyl-benzene (5c-Z)
(FAB) [(M+H)+] calcd for C24H49O5P1: 449.3396; found:
449.3396.
1
Yield: 24%. H NMR:  1.62 (dd, J = 6.8 Hz, J = 1.7 Hz,
3H), 4.44 (m, 1H), 4.78 (s, 2H), 6.0 (dd, J = 6.2 Hz, J=1.7
Hz, 1H), 7.33 (m, 5H arom.). HRMS (FAB) [(M+H)+] calcd
for C10H12O : 148.0888; found: 148.0889.
2.6 Preparation of 5a-e and 5i-k
To a solution of 4a–e-syn and 4i–k-syn (0.5 mmol) in dry
THF at 0 °C was added a solution of t-BuOK 1 M in THF
(1 mL, 1 mmol). After 40 min at 0 °C, the solvent was
evaporated in vacuo. The crude product was then purified
by chromatography on silica gel (Pentane) to afford 5a–e
and 5i–k.
1-Propenyloxy-trans-hex-2-ene (5d-E)
Yield: 30%. IR (CCl4): 1670. 1H NMR:  0.91 (t, J=7.4 Hz,
3H), 1.41 (m, 2H), 1.56 (dd, J = 6.7 Hz, J = 1.6 Hz, 3H),
2.06 (dt, J=5.7 Hz, J=6.5 Hz, 2H), 4.12 (d, J=5.9 Hz, 2H),
4.81 (qd, Jtrans = 12.5 Hz, J=6.7 Hz, 1H), 5.65 (m, 2H), 6.22
(qd, J = 12.5 Hz, J = 1.5 Hz, 1H). 13C NMR:  12.64, 13.71,
24.82, 34.41, 70.14, 77.26, 99.09, 125.39, 135.27. HRMS
(FAB) [(M+H)+] calcd for C9H16O: 141.1279; found:
141.1279.
Hexadec-1-enyloxymethyl-benzene (5a-E)
1
Yield: 70%. H NMR:  0.88 (t, J = 6.4 Hz, 3H), 1.25 (m,
24H), 1.91 (q, J = 6.7 Hz, 2H), 4.70 (s, 2H), 4.88 (dt, J =
12.6 Hz, J = 7.3 Hz, 1H), 6.31 (d, 1H), 7.35 (m, 5H). Anal.
calcd for C23H38O: C, 83.37; H, 11.59; found: C, 83.14; H,
11.34.
1-Propenyloxy-cis-hex-2-ene (5e-E)
Yield: 40%. IR (CCl4): 1655. 1H NMR:  0.92 (t, J=7.3 Hz,
3H), 1.41 (m, 2H), 1.56 (dd, J = 6.7 Hz, J = 1.6 Hz, 3H),
2.06 (dt, J=5.7 Hz, J=6.5 Hz, 2H), 4.23 (d, J=5.1 Hz, 2H),
4.81 (qd, Jtrans = 12.6 Hz, J=6.7 Hz, 1H), 5.65 (m, 2H), 6.23
(qd, Jtrans = 12.6 Hz, J = 1.4 Hz, 1H). 13C NMR:  12.64,
13.74, 22.65, 29.74, 64.96, 98.94, 125.26, 133.85, 146.21.
HRMS (FAB) [(M+H)+]: calcd for C9H16O: 141.1279;
found: 141.1283.
Hexadec-1-enyloxymethyl-benzene (5a-Z)
1
Yield: 40%. H NMR:  0.88 (t, J = 6.4 Hz, 3H), 1.25 (m,
24H), 2.09 (m, 1H), 4.37 (q, J = 7.0 Hz, 1H), 4.78 (s, 2H),
6.0 (dt, J=6.3 Hz, J=1.4 Hz, 1H), 7.31 (m, 5H). Anal. calcd
for C23H38O: C, 83.37; H, 11.59; found: C, 83.06; H, 11.28.
4-Hexadec-1-enyloxymethyl-2,2-dimethyl-[1,3]dioxolane (5b-E)
1-Propenyloxy-hexadec-1-ene (5i-E)
Yield: 82%. IR (CCl4): 1655. 1H NMR:  0.86 (t, J=7.2 Hz,
3H), 1.27 (m, 24H), 1.37 (s, 3H), 1.43 (s, 3H), 1.89 (q, J=
6.5 Hz, 2H), 3.63 (AB, J=5.6 Hz, 1H), 3.71 (AB, J=5.6 Hz,
1H), 3.77 (q, J = 6.2 Hz, 1H), 4.08 (q, J = 6.4 Hz, 1H), 4.33
(dt, J = 5.9 Hz, 1H), 4.28 (dt, J = 14.7 Hz, J = 7.4 Hz, 1H),
6.25 (d, J = 12.6 Hz, 1H). 13C NMR:  14.14, 22.73, 23.94,
25.39, 25.38, 26.71, 29.32, 29.40, 29.56, 29.70, 29.74,
30.67, 66.74, 72.27, 74.12, 109.52, 15.82. Anal. calcd for
C22H42O3: C, 74.52; H, 11.94; found: C, 74.40; H, 11.82.
Yield: 69%. IR (CCl4): 1670. 1H NMR:  0.89 (t, J=7.2 Hz,
3H), 1.27 (m, 24H), 1.89 (m, 2H), 4.19 (dt, J =12.5 Hz, J=
7.4 Hz, 1H), 4.82 (dd, J = 5.4 Hz, J = 1.5 Hz, 2H), 5.22
(ABX, Jcis = 10.4 Hz, J = 2.4 Hz, 1H), 5.31 (ABX, Jtrans
=
4
17.3 Hz, J = 2.4 Hz, J = 1.5 Hz, 1H), 5.95 (ddt, Jtrans =17.2
Hz, Jcis = 10.6 Hz, J = 5.4 Hz, 1H), 6.23 (d, Jtrans = 12.5 Hz,
1H). 13C NMR:  14.15, 22.74, 29.07, 29.42, 29.55, 29.75,
30.72, 31.98, 70.05, 105.14, 117.27, 133.78, 145.56. HRMS
(FAB) [(M+H)+] calcd for C19H36O1: 281.2844; found:
281.2845.
4-Hexadec-1-enyloxymethyl-2,2-dimethyl-[1,3]dioxolane (5b-Z)
1
1-trans-Hex-2-enyloxy-hexadec-1-ene (5j-E)
Yield: 36%. H NMR:  0.86 (t, J = 7.2 Hz, 3H), 1.27 (m,
1
Yield : 68%. IR (CCl4): 1670. H NMR:  0.91 (m, 6H),
24H), 1.37 (s, 3H), 1.42 (s, 3H), 2.05 (q, J = 6.6 Hz, 2H),

DAYOUB Wissam, et al. Sci China Chem September (2010) Vol.53 No.9
1943
1
1.41 (m, 26H), 1.92 (m, 2H), 2.04 (dt, J=7.3 Hz, J=6.7 Hz,
2H), 4.12 (d, J = 5.9 Hz, 2H), 4.81 (dt, J = 12.5 Hz, J = 7.3
Hz, 1H), 5.58 (m, 1H), 5.75 (dtt, Jtrans =15.4 Hz, 3J=6.4 Hz,
J = 5.9 Hz, 1H), 6.22 (d, Jtrans = 12.5 Hz, 1H). 13C NMR: 
13.68, 14.15, 22.21, 22.74, 27.81, 29.08, 29.43, 29.57,
29.73, 29.76, 30.77, 31.99, 34.42, 70.02, 104.85, 125.43,
135.10, 145.61. HRMS (FAB) [(M+H)+] calcd for C22H42O1:
323.3314; found: 323.3313.
82/18 (this ratio was determined from the H NMR spec-
trum of the mixture). The anti stereochemistry was assigned
to the major isomer assuming that the O-alkyl group does
not interfere with the usual chelation and that the hydride
had been delivered from the less hindered face of the inter-
mediate chelate (Scheme 3, TS-1) (this assignment was fur-
ther confirmed on the basis of the configuration of the
enol-ethers double bonds). Slightly higher yield and stereo-
selectivity (86%, anti/syn = 90/10, Table 1) were observed
when we used CaCl2 as the chelating agent [12].
3 Results and discussion
Reduction of 3a with toluene solution of DiBAL [11c]
at 60 °C led to the sole syn isomer in 88% yield. The ob-
served syn stereoselectivity in this case could be explained
in assuming that in the absence of a chelating agent, the
reduction takes place through the Felkin-Anh transition state
structure in which the largest and electron-withdrawing
phosphonate group occupies a position perpendicular to-
ward the carbonyl group (Scheme 3, TS-2) [13].
The Wittig reaction was first conducted on 4a-syn sepa-
rated from the 4a-anti and 4a-syn mixture by acetylation of
alcohol 4a and column chromatography (we were able to
obtain pure 4a-anti and 4a-syn by acetylation (AcCl, Pyr) of
alcohols 4a, separation of the corresponding stereoisomeric
acetates by column chromatography followed by metha-
nolysis (MeONa cat, MeOH) of the ester function). A limited
3.1 Enol ethers from -alkoxy--ketophosphonates
As we intended, in particular, to apply the sequence de-
picted in Scheme 1 for the preparation of (Z) 1-O-alkenyl-2-
acyl-syn-glycerophosphocholines [9] the first experiments
were conducted on diazo ketophosphonate 2a bearing a
fatty alkyl chain. This compound was obtained under re-
ported conditions [6a] from ketophosphonate 1a prepared
by reaction of the lithio-derivative of trimethylphosphonate
on methyl pentadecanoate. In order to test the feasibility of
the stereoselective reduction, we prepared the model com-
pound 3a by the rhodium assisted decomposition of 2a in
the presence of benzyl alcohol (2 equiv) in refluxing toluene
(Scheme 2) [10].
The reduction of 3a into either syn or anti alcohol 4a was
carried out following the experimental conditions reported
previously for similar stereoselective reduction of -keto-
phosphine oxides or -keto phosphonamidates [11]. Treat-
ment of 3a with NaBH4 in the presence of CeCl3 [11a] gave
4a in 83% yield as a mixture of two isomers in the ratio
Scheme 3 Proposed transition states for the stereoselective reduction of
alkoxyketophosphonates 3 by either NaBH4/CaCl2 (TS-1) or DIBAL
(TS-2). Compounds 3 and 4 are racemic mixtures.
Table 1 Enol ethers 5 from alkoxyketophosphonates 3a–c
34
34
45
Yield (%) (E/Z)
3
NaBH4/CaCl2 Yield (%) DIBAL Yield (%)
(syn/anti)
(syn/anti)
3a
86%
88%
4a-syn70% (100/0)
4a-anti40% (5/95)
4b-syn82% (100/0)
4b-anti36% (12/88)
4c-syn45% (100/0)
4c-anti24% (5/95)
(10/90)
78%
(100/0)
65%
3b
3c
(5/95)
97%
(100/0)
50%
Scheme 2 Synthesis of alkoxyphosphonates 3a–c. (a) K2CO3 (1.1 equiv),
TsN3 (1.1 equiv), CH3CN (K2CO3 was replaced by NaH which was used
for the synthesis of 2b). (b) Rh2(OAc)4 (0.5 mol%), R2-OH, PhCH3..
(35/65)
(100/0)

1944
DAYOUB Wissam, et al. Sci China Chem September (2010) Vol.53 No.9
investigation of optimum reaction conditions was carried
out by varying both the nature of the base (NaH, t-BuOK,
LDA) and/or the solvent (pentane, THF, DMF). The best
results were observed when a THF solution of 4a-syn was
submitted to the action of a THF solution of t-BuOK. Under
these conditions, after stirring at 0 °C for 30 min, pure
enol ether 5a-E was obtained in 70% yield after column
chromatography (The presence of the Z isomer could not be
alcohols was carried out on 2c easily prepared in large
amounts from commercially available dimethyl acetylmeth-
ylphosphonate 1c. The results are summarized in Scheme 4.
With primary alcohols the reaction gave the expected allyl-
ethers 3d and 3e in good yields (in the case of reactions
performed with allylic alcohol, besides compounds 3, we
isolated a small amount of com-pounds resulting from in-
sertion of diazo compounds into some residual water). We
did not observe the competitive addition reaction of the in-
termediate rhodium-carbenoid species on the carbon-carbon
double bond, as reported for diazo-keto-esters [16]. With
secondary alcohols, the reaction gave a mixture of the inser-
tion reaction products 3f and 3g and of allylic esters 6f and
6g resulting from a competitive Wolff rearrangement [17].
Finally, with the tertiary alcohol, a mixture mainly consist-
ing of the ester 6h besides a small amount of insertion
product 3h was obtained in a low yield.
1
detected, neither by TLC nor in the H NMR spectrum of
the crude product).
By contrast, when 4a-anti was submitted to the same ex-
perimental conditions it gave 5a in only 40% yield as a
mixture of stereoisomers in the ratio Z/E =95/5. Attempts to
increase this yield either by raising the temperature or by
changing the nature of the solvents or of the base were un-
successful.
Similar results were obtained from ketophosphonate 3b
bearing a protected glyceridic moiety (Table 1). The pure
4b-syn, obtained as described above for 4a, and the mixture
of 4b-anti/4b-syn: 95/5 were involved in the Wittig reaction.
Submitted to the action of a base, they gave pure 5b-E in
82% yield and a mixture of 5b-Z and 5b-E (E/Z = 12/88) in
36% yield. In the above experiments, the lower yields ob-
served when the Wadsworth-Emmons reaction was per-
formed from 4a (or 4b) anti, compared to 4a (or 4b) syn,
might be due to the steric repulsion of the fatty acid chain
and the alkoxy groups in the transition state issued from the
former compounds. However, when we performed the same
experiments from the less hindered 4c bearing a methyl
group instead of the long alkyl chain, surprisingly both the
(Z) and (E) corresponding enol ethers were obtained in
lower yields (Table 1).
In view of these preliminary results, further insertion re-
actions with diazo 2a (R1 = CH3(CH2)12CH2) were con-
ducted exclusively with primary allylic alcohols and gave
the expected insertion reaction products 3i and 3j in indi-
cated yields (Scheme 5).
As shown in Table 2, the reduction of ketophosphonates
From these results it appears that only (E) enol ethers can
be obtained stereoselectively in reasonable yields by con-
ducting a Wadsworth-Emmons reaction on pure syn
-alkoxy--ketoalcohols. The same reaction, applied to
anti- isomers, gave a mixture of stereoisomeric enol ethers
in only moderate to poor yields. Thus in this case, the base
catalyzed isomerization of the hydroxy phosphonates 4-anti
into 4-syn via a retro-aldol type process precedes the
Wadsworth-Emmons reaction [14].
Scheme 4 Insertion reactions of -diazo--ketophosphonate 2b into the
hydroxyl bond of primary, secondary and tertiary allylic alcohols.
3.2 (E) Allyl-vinyl ethers from -allyloxy -keto-
phosphonates
Over the years the Claisen rearrangement has emerged as a
powerful synthetic tool for the stereoselective creation of a
carbon-carbon bond [15]. In this sigmatropic transposition,
the enol is the key step to control the stereochemistry of the
new chiral centers. We therefore decided to examine to
what extend the sequence of Scheme 1 would allow the
stereoselective preparation of allyl vinyl ethers with a (E)
configuration for the vinylic double bond.
Scheme 5 Insertion reactions of -diazo--ketophosphonates (2a) into
the hydroxyl bond of primary allylic alcohols.
Table 2 Allyl-vinyl ethers from -allyloxy--hydroxyphosphonates 3
5-E Yield
30%
3
4-syn Yield
87%
3d
3e
3i
66%
40%
70%
69%
The preliminary study of the insertion reaction of diazo
ketophosphonates into the hydroxyl bond of different allylic
3j
80%
68%

DAYOUB Wissam, et al. Sci China Chem September (2010) Vol.53 No.9
1945
dron Lett, 2001, 42: 8455–8457; b) Dayoub W, Diab Y, Doutheau A.
2-phosphono cyclopenten-2-ones from -tert-butyldimethylsilyloxy-
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3d–e and 3i–j with DIBAL gave the corresponding hy-
droxy-phosphonates 4 in good yields and complete syn
stereoselectivity. When submitted to the action of a com-
mercially available THF solution of t-BuOK, these com-
pounds led to the corresponding pure enol ethers (E) 5 in
moderate to good yields.
7
4 Conclusions
Though Wittig type olefination reaction is among the most
effective methods for the formation of carbon-carbon double
bonds with either (Z) or (E) stereochemistry, the stereose-
lective preparation of O-alkyl enol ethers using this meth-
odology is limited. This seems to be partially due to diffi-
culties encountered in obtaining the Wittig precursors. In
the present work, we have shown that the three-step se-
quence: insertion reaction of a diazo ketophosphonate into
the hydroxylic bond of a primary alcohol, DIBAL reduction
of the alkoxyketophosphonate thus obtained and Wadsworth-
Emmons elimination reaction, led to the corresponding (E)
enol ethers in moderate to good yields. In certain cases this
approach could be a valuable complement of existing
methods.
8
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5
6