Metallo-phosphorylation of alkenes: a highly regioselective reaction of zirconocene-alkene complexes with chlorophosphate

Article abstract of DOI:10.1016/j.tet.2006.04.048

Zirconocene-alkene complexes Cp₂Zr(CH₂{double bond, long}CHR) reacted with chlorophosphate to form zircono-ethylphosphonate with high regioselectivity, which is versatile and could be converted into various functionalized organophosphonates.

Full text of DOI:10.1016/j.tet.2006.04.048

Tetrahedron 62 (2006) 6295–6302
Metallo-phosphorylation of alkenes: a highly regioselective
reaction of zirconocene–alkene complexes with chlorophosphate
a
a
Chunbo Lai,a Chanjuan Xi,a,b, Weixuan Chen and Ruimao Hua
*
aKey Laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education),
Department of Chemistry, Tsinghua University, Beijing 100084, China
bState Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
Received 27 January 2006; revised 12 April 2006; accepted 17 April 2006
Available online 8 May 2006
Abstract—Zirconocene–alkene complexes Cp2Zr(CH2]CHR) reacted with chlorophosphate to form zircono-ethylphosphonate with high
regioselectivity, which is versatile and could be converted into various functionalized organophosphonates.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
reaction of zirconocene–alkene complexes Cp2Zr(CH2]
CHR) with chlorophosphate to form zircono-ethylphospho-
nate 1 or three-membered zirconacycle 2 (Scheme 1). This
result is useful for the preparation of variously functional-
ized organophosphonates RP(O)(OR0)2.
Phosphorylation of unsaturated substrates is an attractive re-
action for the synthesis of organophosphonates RP(O)(OR0)2
that are useful intermediates in organic synthesis.1
Particularly interesting and challenging in the reaction are
the simultaneous introduction of phosphonate and other
functional groups to multiple carbon–carbon bonds.2 The
metallo-phosphorylation is especially interesting, as it is
a more versatile and elegant synthetic elaboration, although
hydrophosphinylation of alkenes,3 and hydrophosphorylation
of alkenes,4 and hydrophosphorylation of allenes5 have been
reported.
R
R = H, Alkyl
Cp2Zr
Cl
P(O)(OR')2
R
ClP(O)(OR')2
1
Cp2Zr
R
R = Aryl
Cp2Zr
P(O)(OR')2
2
Zirconocene–alkene complexes have been attractive com-
pounds in organic synthesis since they can be easily prepared
by several methods such as (1) addition of alkenes to
Cp2ZrBu2 (Negishi reagent),6 (2) a b-hydrogen abstraction
and an elimination of alkanes from zirconocenedialkyls,7
(3) addition of alkenes to Cp2Zr(PMe3)2,8 and (4) replace-
ment of alkenes in zirconocene–alkene complexes
Cp2Zr(alkene)(PR3).9 A number of reactions of zircono-
cene–alkene complexes with unsaturated substrates such as
alkenes10 or aldehydes or ketones11 have been studied.
Recently, we reported a metallo-phosphorylation of ethylene
based on the reaction of zirconocene–ethylene complex
Cp2Zr(CH2]CH2) with chlorophosphate.12 In the course
of further investigations, we found a highly regioselective
Scheme 1.
2. Results and discussion
To a solution of zirconocene–butene complex Cp2Zr(CH2]
CHEt),6 generated by the reaction of Cp2ZrCl2 with 2 equiv
of n-BuLi in THF, was added 1 equiv of diethyl chlorophos-
phate. The reaction mixture was kept at 0 ꢀC for 6 h, and
then it was quenched with 3 N HCl. Purification of crude
product was carried out by column chromatography on silica
gel. Diethyl butylphosphonate 3a was exclusively obtained
in 31P NMR yield of 65% (isolated yield 58%) with excellent
regioselectivity. Deuteriolysis and iodinolysis of the reaction
mixture afforded deuterated compound 4a in 57% yield with
95% deuterium incorporation and iodinated product 5a in
51% yield, respectively (Scheme 2). The formation of 4a
and 5a indicated that zirconium-containing complex 1a
Keywords: Organophosphonate; Alkenes; Metallo-phosphorylation;
Regioselectivity; Zirconocene–alkene.
* Corresponding author. Tel.: +86 10 62782695; fax: +86 10 62618239;
e-mail: cjxi@tsinghua.edu.cn
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.048

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C. Lai et al. / Tetrahedron 62 (2006) 6295–6302
Ar
(R¼Et) was formed as an intermediate. Moreover, addition
of acyl chloride to the reaction mixture in the presence of
CuCl afforded compound 6a in 55% isolated yield, in which
a new carbon–carbon bond was formed.
H3O+
P(O)(OEt)2
8a: Ar = Ph, 65%
Ar
ClP(O)(OEt)2
8b: Ar = 4-Me-Ph, 70%
8c: Ar = 4-Cl-Ph, 48%
Cp2Zr
R
H3O+
Ar
P(O)(OEt)2
D
D3O+
Ar
P(O)(OEt)2
H
P(O)(OEt)2
No
D
3a: R = Et, 58%
3b: R = Hex, 39%
3c: R = H, 63%
D
4b
R
D
R
I
9a: Ar = Ph, 67%
D3O+
Scheme 4.
P(O)(OEt)2
4a: R = Et, 57%
R
ClP(O)(OEt)2
0°C, 6h
Cp2Zr
It is interesting to note that treatment of the reaction mixture
of Cp2Zr(CH2]CHAr) and chlorophosphate with iodine
or NCS afforded diethyl E-2-arylethenylphosphonate in
moderate yields (Scheme 5). No formation of halogenated
organophosphonates was observed.
I2
P(O)(OEt)2
5a: R = Et, 51%
5b: R = Hex, 35%
5c: R = H, 60%
R
PhCOCl
CuCl
O
P(O)(OEt)2
Ph 6a: R = Et, 55%
Ar
Ar
1) ClP(O)(OEt)2
Cp2Zr
Scheme 2.
2) I2 or NCS
P(O)(OEt)2
10
Similar types of products 3b, 5b, 3c, and 5c were obtained
for reaction of zirconocene–octene complex Cp2Zr(CH2]
CHHex) or zirconocene–ethylene Cp2Zr(CH2]CH2)13 and
chlorophosphate.
10a: Ar = Ph, 47%
10b: Ar = 4-Me-Ph, 49%
10c: Ar = 4-Cl-Ph, 30%
Scheme 5.
Moreover, when the reaction mixture of zirconocene–butene
or zirconocene–octene complex with chlorophosphate was
warmed to room temperature and kept for 24 h (Scheme 3),
allylphosphonate 7 was obtained. This result further con-
firmed that the intermediate 1 was formed when reaction
mixture was kept at 0 ꢀC. Then, a b-hydrogen abstraction
and elimination of Cp2ZrHCl afforded allylphosphonate 7
slowly after the reaction mixture was warmed to room tem-
perature. It was noteworthy that in this case HP(O)(OEt)2
was obtained as indicated by 31P NMR.
To further confirm the reaction intermediate, the reaction
of Cp2Zr(CH2]CHC6H4Me) and chlorophosphonate was
carried out at 5 ꢀC for 6 h and followed by addition of
alkyne. The compounds 11 and 12 or 13 and 14 were formed
after hydrolysis (or deuteriolysis) of the reaction mixture
(Scheme 6).
R''
PhMe
P(O)(OEt)2
D
D
D
D
and
PhMe
P(O)(OEt)2
R'
R"
13
R
14
D3O+
ClP(O)(OEt)2
Cp2Zr
+
HP(O)(OEt)2
R''
PhMe
RT, 24h
P(O)(OEt)2
7
P(O)(OEt)2
PhMe
1) ClP(O)(OEt)2
and
Cp2Zr
R''
Cp2Zr
H3O+
Cp2Zr
2)
7a: R = Et, R' = Me, 57%, Z/E = 5:1
7b: R = Hex, R' = Pent, 30%, Z/E = 5:1
R"
PhMe
P(O)(OEt)2
R"
Scheme 3.
PhMe
P(O)(OEt)2
To extend the scope of the title reaction, we tested
Cp2Zr(CH2]CHAr) and chlorophosphonate under opti-
mized reaction conditions (Scheme 4). Treatment of zircono-
cene–styrene complex, generated by addition of styrene to
Negishi reagent6 with diethyl chlorophosphonate at 5 ꢀC
for 14 h afforded diethyl 2-phenylethylphosphonate 8a in
65% yield after hydrolysis. To our surprise, deuteriolysis
of reaction mixture instead of hydrolysis afforded diethyl
1,2-deuterium-2-phenyl-ethylphosphonate 9a in 67% yield
with 85% deuterium incorporation. No formation of 4b
was observed. This result showed that the product of the
reaction Cp2Zr(CH2]CHPh) with chlorophosphate before
hydrolysis contained two Zr–C bonds. It was noteworthy
that in this case only small amount of product 8a was
observed.
and
PhMe
P(O)(OEt)2
R"
11
12
the mixture of 11a and 12a:
the mixture of 11b and 12b:
the mixture of 13a and 14a:
R'' = C4H9, 38%, 11a/12a = 2:1
R'' = Ph, 35%, 11b/12b = 3:1
R'' = C4H9, 35%, 13a/14a = 2:1
Scheme 6.
On the basis of the results obtained above, a plausible reac-
tion mechanism was shown in Scheme 7. In the first step, the
zirconocene–alkene complex reacted with chlorophospho-
nate to form five-membered zirconacycle 15. Then, elimina-
tion of chloride ion from zirconacycle took place to form
zircono-ethylphosphonate 1, which could be converted into

C. Lai et al. / Tetrahedron 62 (2006) 6295–6302
6297
R
E
P(O)(OR')2
R = H, Alkyl
E+
R
R
R
ClP(O)(OR')2
Cp2Zr
Cp2Zr
Cl
P(O)(OR')2
Cp2Zr
OR'
OR'
P
Cl
O
R''
P(O)(OEt)2
1
Cp2ZrHCl
R = Alkyl
15
R = Aryl
HCl
R
R
P(O)(OR')2
D
D3O+
Cp2Zr
D
P(O)(OR')2
2
9
R"
R"
R
R
X
R
P(O)(OR')2
P(O)(OR')2
X
Cp2Zr
or
and
Cp2Zr
Cp2Zr
D+
X
Cp2Zr
R
P
OEt
X
P
O
OEt
O
OEt
OEt
P(O)(OR')2
R"
17
19
16
18
R"
R
Cp2ZrX2
R
D
D
D
D
and
R
P(O)(OR')2
P(O)(OR')2
R"
10
13
14
Scheme 7.
functionalized ethylphosphonate derivatives by coupling
with various electrophiles when substituted R is hydrogen
or alkyl groups. When R is aryl group, the conjugative effect
of aryl group and electron-withdrawing effect of phosphate
group favor b-H elimination to form intermediate 2, which
can be confirmed by further deuteriolysis to form compound
9 or coupling with terminal alkyne to produce compound 13
and 14 after deuteriolysis. The intermediate 2 could react
with I2 or NCS to form intermediate 18 or 19, which would
easily eliminate Cp2ZrX2 to form compound 10.
using 85% H3PO4 (dP¼0) as an internal standard. Mass
spectra were obtained using a Bruker Esquire iontrap mass
spectrometer in positive ion mode.
4.2. A procedure for the reaction of Cp2Zr(CH2]
CHCH2CH3) with chlorophosphate: preparation of
2-zircono-n-butylphosphonate
To a solution of dibutylzirconocene, generated by the reac-
tion of Cp2ZrCl2 with 2 equiv of BuLi (1.5 mL, 1.6 M in
hexane solution) in THF was added 1.0 mmol diethyl chloro-
phosphate (144.6 mL) at ꢁ78 ꢀC. The reaction mixture was
warmed to 0–5 ꢀC and stirred at the same temperature for
6 h (31P NMR yield in 65%). 31P NMR (81 MHz, THF,
85% H3PO4) d 36.8 ppm.
3. Conclusion
In summary, we developed a versatile reaction to synthesize
various functionalized organophosphonates RP(O)(OR0)2 via
highly regioselective metallo-phosphorylation of alkenes.
A detailed study on the reaction process is also presented.
4.2.1. Preparation of diethyl n-butylphosphonate (3a).14
The resulting mixture of 2-zircono-n-butylphosphonate
was treated with 3 N HCl. Product was extracted with ethyl
acetate and the organic extract was dried over MgSO4.
Removal of the solvent and subsequent purification by col-
umn chromatography on silica gel (ethyl acetate/petroleum
ether¼3/1) afforded 113 mg of the title compound as a color-
less liquid (isolated yield 58%). 1H NMR (300 MHz, CDCl3,
4. Experimental
4.1. General
All manipulations were conducted in pre-dried Schlenk tube
and under nitrogen with a slightly positive pressure. The re-
action progress was monitored by 31P NMR. The 31P NMR
yield of the products was obtained in proportion to the inte-
gral area of corresponding products. Unless otherwise noted,
all starting materials were commercially available and were
used without further purification. Tetrahydrofuran (THF)
was refluxed and freshly distilled from dark purple solutions
of sodium and benzophenone under a nitrogen atmosphere.
1H NMR and 13C NMR spectra were recorded on JOEL
300 NMR spectrometer with TMS as internal standard.
31P NMR spectra were recorded on Bruker AC 200 NMR
spectrometer at 81 MHz under 1H decoupled conditions
3
3
Me4Si) d 0.85 (t, JHH¼7.2 Hz, 3H), 1.25 (t, JHH¼6.9 Hz,
6H), 1.30–1.37 (m, 2H), 1.50–1.56 (m, 2H), 1.58–1.72
(m, 2H), 4.01–4.06 (m, 4H); 13C NMR (75 MHz, CDCl3,
3
Me4Si)
d
13.4, 16.3 (d, JPC¼5.7 Hz), 23.9 (d,
3JPC¼17.2 Hz), 24.3, 25.2 (d, JPC¼142.7 Hz), 61.2 (d,
2JPC¼6.5 Hz); 31P NMR (81 MHz, CDCl3, 85% H3PO4)
d 33.5. Positive ion ESI-MS, m/z¼217.0 (M+Na+). HRMS
calcd for C8H19O3P, 194.1072; found, 194.1075.
1
4.2.2. Preparation of diethyl 2-deuterium-n-butylphos-
phonate (4a). The reaction was carried out in a similar way
to that described above using 20% DCl instead of 3 N HCl

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C. Lai et al. / Tetrahedron 62 (2006) 6295–6302
to quench the reaction mixture and stirred for 3 h at room tem-
perature (isolated yield: 57%). H NMR (300 MHz, CDCl3,
the organic extract was dried over MgSO4. Removing the
solvent and subsequent purification by column chromato-
graphy on silica gel (ethyl acetate/petroleum ether¼2/1)
afforded 109.5 mg of the title compound as a colorless liquid
(yield 57%, Z/E¼5:1). Major isomer—diethyl (Z)-2-bute-
nylphosphonate:16 1H NMR (300 MHz, CDCl3, Me4Si)
1
3
3
Me4Si) d 0.92 (t, JHH¼7.2 Hz, 3H), 1.33 (t, JHH¼6.9 Hz,
6H), 1.37–1.42 (m, 2H), 1.48–1.62 (m, 1H), 1.72 (dd,
2
3JHH¼7.5 Hz, JPH¼18.0 Hz, 2H), 4.02–4.16 (m, 4H); 13C
NMR (75 MHz, CDCl3, Me4Si)
d 13.4, 16.4 (d,
3
3
4
3JPC¼5.7 Hz), 23.5 (d, JPC¼17.2 Hz), 23.7–24.2 (m),
d 1.34 (m, 6H), 1.67 (dd, JHH¼10.2 Hz, JHH¼0.9 Hz,
1
2
2
3
25.2 (d, JPC¼139.8 Hz), 61.3 (d, JPC¼6.5 Hz); 31P NMR
(81 MHz, CDCl3, 85% H3PO4) d 33.6. Positive ion ESI-
MS, m/z¼196.0 (M+H+), 217.9 (M+Na+). HRMS calcd for
C8H18DO3P, 195.1135; found, 195.1139.
3H), 2.62 (dd, JPH¼22.2 Hz, JHH¼7.5 Hz, 2H), 4.06–
4.16 (m, 4H), 5.42–5.48 (m, 1H), 5.58–5.71 (m, 1H); 13C
4
NMR (75 MHz, CDCl3, Me4Si) d 12.9 (d, JPC¼2.2 Hz),
3
1
16.5 (d, JPC¼6.2 Hz), 25.5 (d, JPC¼139.9 Hz), 61.9
2
2
(d, JPC¼6.8 Hz), 118.7 (d, JPC¼11.2 Hz), 128.7 (d,
3JPC¼14.3 Hz); 31P NMR (81 MHz, CDCl3, 85% H3PO4)
d 28.3. Positive ion ESI-MS: m/z¼192.8 (M+H+), 214.7
(M+Na+). HRMS calcd for C8H17O3P, 192.0915; found,
192.0913.
4.2.3. Preparation of diethyl 2-iodo-n-butylphosphonate
(5a).15 The reaction was carried out in a similar way to
that described above using I2 (1.0 mmol, 254 mg) instead
of 3 N HCl and the reaction mixture was stirred for 6 h at
room temperature. The resulting mixture was treated with
3 N HCl and Na2S2O3 solution. Product was extracted
with ethyl acetate and the organic extract was dried over
MgSO4. Removal of the solvent and subsequent purification
by column chromatography on silica gel (ethyl acetate/
petroleum ether¼3/1) afforded 163 mg of the title com-
pound as yellow oil (yield 51%). 1H NMR (300 MHz,
4.3. A procedure for the reaction of Cp2Zr(CH2]
CHHex) with chlorophosphate: preparation of
2-zircono-n-octylphosphonate
To a solution of dibutylzirconocene, generated by the reac-
tion of Cp2ZrCl2 with 2 equiv of BuLi (1.5 mL, 1.6 M in
hexane solution) in THF was added 1.0 equiv of 1-octene
(157 mL) at ꢁ78 ꢀC. The reaction mixture was warmed to
0–5 ꢀC and stirred at the same temperature for 6 h (31P
NMR yield 45%). 31P NMR (81 MHz, THF, 85% H3PO4)
d 36.8 ppm.
3
CDCl3, Me4Si) d 1.04 (t, 3H, JHH¼7.0 Hz), 1.34 (t,
3JHH¼6.9 Hz, 6H), 1.72–2.00 (m, 2H), 2.50–2.70 (m, 2H),
4.01–4.14 (m, 4H), 4.30–4.40 (m, 1H); 13C NMR
3
(75 MHz, CDCl3, Me4Si) d 14.0, 16.3 (d, JPC¼5.7 Hz),
27.9, 33.8 (d, 3JPC¼5.0 Hz), 38.4 (d, 1JPC¼130.3 Hz), 61.5
2
2
(d, JPC¼6.5 Hz), 61.7 (d, JPC¼6.5 Hz); 31P NMR
(81 MHz, CDCl3, 85% H3PO4) d 27.1. Positive ion ESI-
MS: m/z¼321.0 (M+H+). HRMS calcd for C8H18IO3P,
320.0038; found, 320.0035.
4.3.1. Preparation of diethyl n-octylphosphonate (3b).17
The resulting mixture of 2-zircono-n-octylphosphonate
was treated with 3 N HCl. Product was extracted with ethyl
acetate and the organic extract was dried over MgSO4.
Removing the solvent and subsequent purification by col-
umn chromatography on silica gel (ethyl acetate/petroleum
ether¼3/1) afforded 97 mg of the title compound as a color-
less liquid (yield 39%). 1H NMR (300 MHz, CDCl3, Me4Si)
d 0.88 (t, 3JHH¼6.3 Hz, 3H), 1.26–1.35 (m, 16H), 1.46–1.78
4.2.4. Preparation of diethyl 2-benzoyl-n-butylphospho-
nate (6a). After addition of CuCl (1.0 mmol, 99 mg) to the
reaction mixture of zircono-2-butylphosphonate at room
temperature, benzoyl chloride (1.0 mmol, 116 mL) was
added and the reaction mixture was stirred at 50 ꢀC for
12 h. The resulting mixture was treated with 3 N HCl at
room temperature. Product was extracted with ethyl acetate
and the organic extract was dried over MgSO4. Removal of
the solvent and subsequent purification by column chroma-
tography on silica gel (ethyl acetate/petroleum ether¼3/1)
yielded 164 mg of the title compound as a colorless solid
(yield 55%). 1H NMR (300 MHz, CDCl3, Me4Si) d 0.87 (t,
3JHH¼7.2 Hz, 3H), 1.34 (m, 6H), 1.57–1.97 (m, 2H),
2.38–2.52 (m, 1H), 3.44–3.90 (m, 2H) 3.93–4.04 (m, 4H),
(m, 4H), 4.08–4.13 (m, 4H); 13C NMR (75 MHz, CDCl3,
3
Me4Si)
d
14.1, 16.5 (d, JPC¼5.7 Hz), 22.4 (d,
3JPC¼5.0 Hz), 22.6, 25.7 (d, JPC¼139.1 Hz), 29.1 (2C),
1
30.6 (d, JPC¼17.2 Hz), 31.8, 61.5 (d, JPC¼5.7 Hz); 31P
NMR (81 MHz, CDCl3, 85% H3PO4) d 33.7. Positive ion
ESI-MS: m/z¼251.2 (M+H+), 273.2 (M+Na+). HRMS calcd
for C12H27O3P, 250.1698; found, 250.1695.
3
3
4.3.2. Preparation of diethyl 2-iodo-n-octylphosphonate
(5b). The reaction was carried out in a similar way to that
described above using I2(1.0 mol, 254 mg) instead of 3 N
HCl and the reaction mixture was stirred for 6 h at room
temperature. The resulting mixture was treated with 3 N
HCl and Na2S2O3 solution. Product was extracted with ethyl
acetate and the organic extract was dried over MgSO4.
Removing the solvent and subsequent purification by col-
umn chromatography on silica gel (ethyl acetate/petroleum
ether¼2/1) afforded 132 mg of the title compound as a
yellow oil (yield 35%). 1H NMR (300 MHz, CDCl3, Me4Si)
2
7.45–7.60 (m, 3H), 8.00 (d, 2H, JHH¼8.3 Hz); 13C NMR
3
(75 MHz, CDCl3, Me4Si) d 11.0, 16.2 (d, JPC¼5.7 Hz),
1
3
26.6 (d, JPC¼139.9 Hz), 27.1 (d, JPC¼13.6 Hz), 41.4 (d,
2JPC¼3.6 Hz), 61.5 (d, 2JPC¼6.5 Hz), 61.7 (d,
2JPC¼6.5 Hz), 128.3, 128.6, 133.1, 136.7, 202.0 (d,
3JPC¼5.7 Hz); 31P NMR (81 MHz, CDCl3, 85% H3PO4)
d 31.5. Positive ion ESI-MS, m/z¼305.1 (M+Li+), 321.1
(M+Na+). HRMS calcd for C15H23O4P, 298.1334; found,
298.1338.
3
4.2.5. Preparation of diethyl 2-butenylphosphonate (7a).
To a solution of dibutylzirconocene in THF was added
1.4 equiv of diethyl chlorophosphate (217 mL). The reaction
mixture was warmed to room temperature and kept at the
same temperature for 12 h. The resulting mixture was treated
with 3 N HCl. Product was extracted with ethyl acetate and
d 0.84 (t, JHH¼8.4 Hz, 3H), 1.25–1.37 (m, 14H), 1.69–
1.81 (m, 2H), 2.45–2.68 (m, 2H), 4.08–4.13 (m, 4H),
4.13–4.33 (m, 1H); 13C NMR (75 MHz, CDCl3, Me4Si)
3
d 14.1, 16.5 (d, JPC¼5.9 Hz), 22.6, 26.2, 28.3, 29.7, 31.7,
1
3
38.9 (d, JPC¼139.1 Hz), 40.7 (d, JPC¼5.7 Hz), 62.0 (d,
3JPC¼8.2 Hz), 62.1 (d, JPC¼8.2 Hz); 31P NMR (81 MHz,
3

C. Lai et al. / Tetrahedron 62 (2006) 6295–6302
6299
CDCl3, 85% H3PO4) d 27.1. Positive ion ESI-MS:
m/z¼377.1 (M+H+), 399.1 (M+Na+). HRMS calcd for
C12H26IO3P, 376.0664; found, 376.0668.
Chromatography using a mixture of ethyl acetate and petro-
leum ether (2:1) as elute provided the product as a colorless
liquid 175.2 mg (yield 60%). H NMR (300 MHz, CDCl3,
1
Me4Si) d 1.29 (t, J¼6.9 Hz, 6H), 2.31–2.43 (m, 2H), 3.19–
4.3.3. Preparation of diethyl 2-octenylphosphonate
(7b).18 To a solution of dibutylzirconocene in THF was
added 1.4 equiv of diethyl chlorophosphate (216.9 mL).
The reaction mixture was warmed to room temperature
and kept at the same temperature for 12 h. The resulting mix-
ture was treated with 3 N HCl. Product was extracted with
ethyl acetate and the organic extract was dried over
MgSO4. Removing the solvent and subsequent purification
by column chromatography on silica gel (ethyl acetate/
petroleum ether¼2/1) afforded 75 mg of the title compound
as a colorless liquid (yield 30%, Z/E¼5:1). Major isomer—
diethyl (Z)-2-octenylphosphonate: 1H NMR (300 MHz,
CDCl3, Me4Si) d 0.87 (t, 3JHH¼7.2 Hz, 3H), 1.24–1.60 (m,
12H), 2.03 (m, 2H), 2.59 (dd, 2JPH¼21.9 Hz,
3JHH¼7.5 Hz, 2H), 4.00–4.11 (m, 4H), 5.36–5.42 (m, 1H),
5.55–5.61 (m, 1H); 13C NMR (75 MHz, CDCl3, Me4Si)
d 14.2, 16.5 (d, 3JPC¼5.0 Hz), 22.6, 25.8 (d, 1JPC¼139.5 Hz),
3.28 (m, 2H), 4.05–4.10 (m, 4H); 13C NMR (75 MHz,
2
3
CDCl3, Me4Si) d ꢁ7.4 (d, JPC¼3.8 Hz), 16.4 (d, JPC
¼
1
3
6.3 Hz), 31.9 (d, JPC¼131.7 Hz), 62.0 (d, JPC¼6.8 Hz);
31P NMR (81 MHz, THF, 85% H3PO4) d 27.0. Positive ion
ESI-MS: m/z¼292.9 (M+H+).
4.5. A procedure for the reaction of Cp2Zr(PhCH]
CH2) with chlorophosphate: preparation of diethyl
2-phenyl-1,2-zircono-ethylphosphonate
To a solution of dibutylzirconocene in THF was added
1.0 equiv of styrene and stirred for 1 h at room temperature.
Chlorophosphate (1 mmol, 144.7 mL) was added to this
solution and stirred for 14 h at 0–5 ꢀC (31P NMR yield 58%).
31P NMR (81 MHz, THF, 85% H3PO4) d 49.7 ppm.
4.5.1. Preparation of diethyl 2-phenylethylphosphonate
(8a).21 The resulting mixture of diethyl 2-phenyl-1,2-zir-
cono-ethylphosphonate was treated with 3 N HCl and stirred
for 1 h. Product was extracted with ethyl acetate and the
organic extract was dried over MgSO4. Removing the solvent
and subsequent purification by column chromatography on
silica gel (ethyl acetate/petroleum ether¼2/1) afforded
157.3 mg of the title compound as a colorless liquid (yield
65%). 1H NMR (300 MHz, CDCl3, Me4Si) d 1.25–1.38
(m, 6H), 2.00–2.22 (m, 2H), 2.87–2.96 (m, 2H), 4.05–4.13
(m, 4H), 7.19–7.50 (m, 5H); 13C NMR (75 MHz, CDCl3,
2
27.4, 29.0, 31.6, 61.93 (d, JPC¼5.3 Hz), 117.6
2
3
(d, JPC¼10.5 Hz), 134.8 (d, JPC¼14.3 Hz); 31P NMR
(81 MHz, CDCl3, 85% H3PO4) d 28.8. Positive ion ESI-
MS: m/z¼249.2 (M+H+), 271.1 (M+Na+). HRMS calcd for
C12H25O3P, 248.1541; found, 248.1545.
4.4. A procedure for the reaction of Cp2Zr(CH2]CH2)
with chlorophosphate: preparation of 2-zircono-ethyl-
phosphonate
3
1
To a solution of diethylzirconocene, generated by the reac-
tion of Cp2ZrCl2 with 2 equiv of EtMgBr (2.4 mL, 1 M in
ether solution) in THF was added 1 equiv of diethyl chloro-
phosphate (144.6 mL). The reaction mixture was kept at 5 ꢀC
for 24 h or at room temperature for 12 h or at 40 ꢀC for 3 h
(31P NMR yield 89%). 31P NMR 34.7 (81 MHz, THF, 85%
H3PO4).
Me4Si) d 16.5 (d, JPC¼6.2 Hz), 27.6 (d, JPC¼139.3 Hz),
2
2
28.6 (d, JPC¼4.9 Hz), 61.6 (d, JPC¼6.2 Hz), 126.4,
128.1, 128.6, 140.8 (d, JPC¼15.0 Hz). 31P NMR
3
(81 MHz, CDCl3, 85% H3PO4) d 32.4. Positive ion ESI-
MS: m/z¼242.8 (M+H+), 264.7 (M+Na+). HRMS calcd for
C12H19O3P, 242.1072; found, 242.10726.
4.5.2. Preparation of diethyl 1,2-dideuterium-2-phenyl-
ethylphosphonate (9a). The reaction was carried out in
a similar way to that described above using 20% DCl instead
of 3 N HCl to quench the reaction mixture and stirred for 3 h
at 5 ꢀC (yield: 67% with 85% deuterium incorporation). 1H
NMR (300 MHz, CDCl3, Me4Si) d 1.26–1.36 (m, 6H), 2.02–
2.12 (m, 1.16H), 2.90–2.96 (m, 1.17H), 4.07–4.13 (m, 4H),
7.20–7.31 (m, 5H); 13C NMR (75 MHz, CDCl3, Me4Si)
4.4.1. Preparation of diethyl ethylphosphonate (3c).19
The reaction mixture of zircono-ethylphosphonate was
quenched with 3 N HCl solution and then extracted with ethyl
acetate. The extract was washed with water and dried over
MgSO4. The solvent was evaporated in vacuo to give a light
yellow liquid. Chromatography using a mixture of ethyl ace-
tate and petroleum ether (2:1) as elute provided the product
as a colorless liquid 104.6 mg (yield 63%). 1H NMR
3
1
d
16.3 (d, JPC¼5.7 Hz), 27.2 (dt, JPC¼140.2 Hz,
3
2
1
(300 MHz, CDCl3, Me4Si) d 1.16 (dt, JPH¼19.8 Hz,
1JDC¼19.4 Hz), 28.2 (dt, JPC¼4.6 Hz, JDC¼19.7 Hz),
2
3JHH¼7.8 Hz, 3H), 1.33 (t, J¼7.0 Hz, 6H), 1.72 (q,
61.4 (d, JPC¼6.5 Hz), 126.1, 127.8, 128.3, 140.7 (d,
2JPH¼18.3 Hz, JHH¼7.8 Hz, 2H), 4.06–4.11 (m, 4H); 13C
3JPC¼15.8 Hz), 31P NMR (81 MHz, CDCl3, 85% H3PO4)
d 31.5. Positive ion ESI-MS: m/z¼245.1 (M+H+), 251.1
(M+Li+). HRMS calcd for C12H17D2O3P, 244.1197; found,
244.1194.
3
2
NMR (75 MHz, CDCl3, Me4Si) d 6.6 (d, JPC¼6.1 Hz),
3
1
16.5 (d, JPC¼7.2 Hz), 18.9 (d, JPC¼142.5 Hz), 61.6 (d,
3JPC¼6.2 Hz); 31P NMR (81 MHz, THF, 85% H3PO4)
d 34.7. Positive ion ESI-MS: m/z¼167.0 (M+H+).
4.5.3. Preparation of diethyl (E)-2-phenyl-ethenyl-
phosphonate (10a).2c,22 The resulting mixture of diethyl
2-phenyl-1,2-zircono-ethylphosphonate was treated with
NCS (1 mmol, 133.5 mg) or I2 (1 mmol, 254 mg) and stirred
for 30 min at room temperature. Quenched with 3 N HCl and
product was extracted with ethyl acetate and the organic
extract was dried over MgSO4. Removal of the solvent and
subsequent purification by column chromatography on silica
gel (ethyl acetate/petroleum ether¼2/1) afforded 113 mg of
4.4.2. Preparation of diethyl 2-iodoethylphosphonate
(5c).20 To the reaction mixture of zircono-ethylphosphonate
was added 1.2 equiv of I2 (305 mg) and the reaction mixture
was stirred at room temperature for 3 h. The above reaction
mixture was quenched with 3 N HCl, and stirred at room
temperature for 1 h and then extracted with ethyl acetate.
The extract was washed with water and dried over MgSO4.
The solvent was evaporated in vacuo to a light brown liquid.

6300
C. Lai et al. / Tetrahedron 62 (2006) 6295–6302
the title compound as a colorless liquid (yield 47%). 1H NMR
subsequent purification by column chromatography on silica
gel (ethyl acetate/petroleum ether¼1/1) afforded 128 mg of
the title compounds of the mixture as oil liquid (yield 38%,
12a/11a¼1:2).
3
(300 MHz, CDCl3, Me4Si) d 1.32 (t, JHH¼6.6 Hz, 6H),
2
3
4.03–4.16 (m, 4H), 6.28 (t, JPH¼17.4 Hz, JHH¼17.4 Hz,
1H), 7.28–7.58 (m, 6H); 13C NMR (75 MHz, CDCl3,
3
2
Me4Si) d 16.5 (d, JPC¼5.6 Hz), 62.0 (d, JPC¼4.5 Hz),
1
114.1 (d, JPC¼193.4 Hz), 127.8, 128.9, 130.3, 134.8 (d,
4.6.3.1. Diethyl 2-(p-tolyl)-oct-3-enylphosphonate
(12a). 1H NMR (300 MHz, CDCl3, Me4Si) d 0.73–0.83
(m, 3H), 1.12–1.24 (m, 4H), 1.25–1.30 (m, 6H), 1.98–2.03
(m, 2H), 2.09–2.26 (m, 2H), 2.26 (s, 3H), 3.50–3.59 (m,
1H), 3.63–4.00 (m, 4H), 5.31–5.59 (m, 2H), 6.94–7.02
(m, 4H); 13C NMR (75 MHz, CDCl3, Me4Si) d 13.8, 16.1–
3JPC¼23.0 Hz), 148.8 (d, JPC¼5.6 Hz); 31P NMR
2
(81 MHz, CDCl3, 85% H3PO4) d 20.2. Positive ion ESI-
MS: m/z¼241.0 (M+H+), 263.0 (M+Na+). HRMS calcd for
C12H17O3P, 240.0915; found, 240.0918.
1
4.6. A procedure for the reaction of Cp2Zr(MePhCH]
CH2) with chlorophosphate: preparation of diethyl
2-(4-methylphenyl)-1,2-zircono-ethylphosphonate
16.4 (m), 20.9, 22.1, 31.6, 32.0, 32.5 (d, JPC¼137.9 Hz),
2
3
42.4 (d, JPC¼3.0 Hz), 61.2 (d, JPC¼6.8 Hz), 61.3
3
(d, JPC¼6.8 Hz), 127.2, 129.0, 130.5, 132.9 (d,
3JPC¼11.3 Hz), 135.8, 141.05 (d, JPC¼9.8 Hz); 31P NMR
3
To a solution of dibutylzirconocene in THF was added
1.0 equiv of 4-methyl-styrene and stirred for 1 h at room
temperature. Chlorophosphate (1 mmol, 144.7 mL) was
added to this solution and stirred for 6 h at 5 ꢀC (31P NMR
yield 70%). 31P NMR (81 MHz, THF, 85% H3PO4)
d 50.1 ppm.
(81 MHz, CDCl3, 85% H3PO4) d 30.6. Positive ion ESI-
MS: m/z¼339.3 (M+H+). HRMS calcd for C19H31O3P,
338.2011; found, 338.2009.
4.6.3.2. Diethyl (4-methyl-benzyl)-hept-2-enylphos-
phonate (11a). 1H NMR (300 MHz, CDCl3, Me4Si) d
0.73–0.83 (m, 3H), 1.12–1.24 (m, 4H), 1.25–1.30 (m, 6H),
1.98–2.03 (m, 2H), 2.23 (s, 3H), 2.60–2.75 (m, 2H), 3.11–
3.18 (m, 1H), 4.06–4.16 (m, 4H), 5.28–5.33 (m, 2H),
6.93–7.02 (m, 4H); 13C NMR (75 MHz, CDCl3, Me4Si)
4.6.1. Preparation of diethyl 2-(4-methylphenyl)ethyl-
phosphonate (8b).23 The resulting mixture of diethyl 2-(4-
methylphenyl)-1,2-zircono-ethylphosphonate was treated
with 3 N HCl and stirred for 1 h. Then it was carried out
in a similar way to that described above to get 179 mg of
4
d 13.7, 16.1–16.4 (m), 20.9, 21.7, 31.1 (d, JPC¼3.0 Hz),
32.1, 34.5 (d, 2JPC¼3.0 Hz), 43.6 (d, 1JPC¼136.6 Hz), 61.7
1
3
3
2
the title compound as a colorless liquid (yield 70%). H
NMR (300 MHz, CDCl3, Me4Si) d 1.32 (m, JHH¼6.9 Hz,
(d, JPC¼6.8 Hz), 62.1 (d, JPC¼6.8 Hz), 123.5 (d, JPC¼
3
3
9.8 Hz), 128.7, 128.9, 135.4, 136.0 (d, JPC¼16.5 Hz),
3
6H), 1.98–2.10 (m, 2H), 2.32 (s, 3H), 2.83–2.92 (m, 2H),
136.1 (d, JPC¼13.5 Hz); 31P NMR (81 MHz, CDCl3, 85%
3
4.10 (t, JHH¼7.0 Hz, 4H), 7.10 (s, 4H); 13C NMR
H3PO4) d 30.0. Positive ion ESI-MS: m/z¼339.3 (M+H+).
3
(75 MHz, CDCl3, Me4Si) d 16.4 (d, JPC¼5.9 Hz), 20.9,
1
2
27.6 (d, JPC¼138.4 Hz), 28.0 (d, JPC¼4.3 Hz), 61.5 (d,
4.6.4. Preparation of diethyl 4-phenyl-2-(p-tolyl)-but-3-
enylphosphonate (12b) and diethyl 1-(4-methyl-benzyl)-
3-phenyl-allyl-phosphonate (11b). The resulting mixture
of diethyl-2-(4-methylphenyl)-1,2-zircono-ethylphosphonate
was added 1.0 mmol phenylacetylene and stirred for 3 h at
room temperature, then treated with 3 N HCl and stirred
for 1 h. The product was extracted with ethyl acetate and
the organic extract was dried over MgSO4. Removing the
solvent and subsequent purification by column chromato-
graphy on silica gel (ethyl acetate/petroleum ether¼1/1)
afforded 132 mg of the title compounds of the mixture as
a colorless solid (yield 37%, 12b/11b¼1:3).
3JPC¼5.7 Hz), 127.8, 129.1, 135.7, 137.8 (d, JPC
¼
3
17.9 Hz) ; 31P NMR (81 MHz, CDCl3, 85% H3PO4) d 31.6.
Positive ion ESI-MS: m/z¼257.1 (M+H+), 279.0 (M+Na+).
HRMS calcd for C13H21O3P, 256.1228; found, 256.1232.
4.6.2. Preparation of diethyl (E)-2-(4-methylphenyl)
ethenylphosphonate (10b).24 The resulting mixture of
diethyl 2-(4-methylphenyl)-1,2-zircono-ethylphosphonate
was treated with NCS (1 mmol, 133.5 mg) or I2 (1 mmol,
254 mg) and stirred for 30 min at room temperature. Then
it was carried out in a similar way to that described above
to get 124.5 mg of the title compound as a colorless liquid
1
(yield 49%). H NMR (300 MHz, CDCl3, Me4Si) d 1.25–
1.35 (m, 6H), 2.37 (s, 3H), 4.03–4.12 (m, 4H), 6.20 (t,
4.6.4.1. Diethyl 1-(4-methyl-benzyl)-3-phenyl-allyl-
phosphonate (11b). 1H NMR (CDCl3, Me4Si) d 1.26–1.36
(m, 6H), 2.29 (s, 3H), 2.83–3.00 (m, 2H), 3.22–3.30 (m,
1H), 4.00–4.20 (m, 4H), 6.00–6.13 (m, 1H), 6.27–6.39
(m, 1H) 7.03–7.32 (m, 9H); 13C NMR (CDCl3, Me4Si)
3
2JPH¼17.5 Hz, JHH¼17.5 Hz), 7.18–7.47 (m, 5H), 13C
3
NMR (75 MHz, CDCl3, Me4Si) d 16.4 (d, JPC¼5.8 Hz,
1
2C), 21.4, 61.9, 112.6 (d, JPC¼190.4 Hz), 127.7, 129.6,
3
2
130.0 (d, JPC¼23.3 Hz), 140.6, 148.8; 31P NMR
d 16.3–16.6 (m), 21.1, 34.8 (d, JPC¼3.8 Hz), 44.3 (d,
(81 MHz, CDCl3, 85% H3PO4) d 21.0. Positive ion ESI-
MS: m/z¼255.2 (M+H+), 277.2 (M+Na+). HRMS calcd for
C13H19O3P, 254.1072; found, 254.1075.
1JPC¼136.3 Hz), 62.2 (d, 3JPC¼7.5 Hz), 62.7 (d,
2
3JPC¼7.5 Hz), 124.2 (d, JPC¼10.8 Hz), 126.3, 127.6,
3
128.5, 129.0, 129.2, 134.6 (d, JPC¼14.3 Hz), 135.8, 135.9
3
4
(d, JPC¼13.5 Hz), 137.0 (d, JPC¼2.3 Hz); 31P NMR
(81 MHz, CDCl3, 85% H3PO4) d 28.9. Positive ion ESI-
MS: m/z¼359.1 (M+H+), 381.1 (M+Na+). HRMS calcd for
C21H27O3P, 358.1698; found, 358.1697.
4.6.3. Preparation of diethyl 2-(p-tolyl)-oct-3-enyl-
phosphonate (12a) and diethyl (4-methyl-benzyl)-hept-
2-enylphosphonate (11a). The resulting mixture of diethyl
2-(4-methylphenyl)-1,2-zircono-ethylphosphonate was added
1.0 mmol 1-hexyne and stirred for 3 h at room temperature,
then treated with 3 N HCl and stirred for 1 h. The product
was extracted with ethyl acetate and the organic extract
was dried over MgSO4. Removing the solvent and
4.6.5. Preparation of diethyl 1,4-dideuterium-2-(p-tolyl)-
oct-3-enylphosphonate (14a) and diethyl 3-deuterium-1-(4-
methylphenyl-deuterium-methyl)-hept-2-enylphosphonate
(13a). The reaction was carried out in a similar way to that

C. Lai et al. / Tetrahedron 62 (2006) 6295–6302
6301
described above using 20% DCl instead of 3 N HCl to
quench the reaction mixture and stirred for 3 h at 5 ꢀC (yield
35%, 14a/13a¼1:2).
was treated with NCS (1 mmol, 133.5 mg) or I2 (1 mmol,
254 mg) and stirred for 30 min at room temperature. Then
it was carried out in a similar way to that described above
to get 82 mg of the title compound as a colorless liquid (yield
4.6.5.1. Diethyl 1,4-dideuterium-2-(p-tolyl)-oct-3-
enylphosphonate (14a). 1H NMR (300 MHz, CDCl3,
Me4Si) d 0.78–0.93 (m, 3H), 1.11–1.24 (m, 4H), 1.26–1.32
(m, 6H), 1.91–2.02 (m, 2H), 2.08–2.22 (m, 1H), 2.29 (s,
3H), 3.66–3.72 (m, 1H), 3.83–4.00 (m, 4H), 5.56 (d,
3JHH¼6.9 Hz, 1H), 7.02–7.08 (m, 4H); 13C NMR (CDCl3,
Me4Si) d 14.0, 16.1–16.4 (m), 21.1, 22.3, 31.5, 32.2,
30%). 1H NMR (300 MHz, CDCl3, Me4Si) d 1.36 (t, 3JHH
¼
2
6.8 Hz, 6H), 4.08–4.18 (m, 4H), 6.23 (t, JPH¼17.3 Hz,
3JHH¼17.3 Hz), 7.13–7.52 (m, 5H); 13C NMR (75 MHz,
3
2
CDCl3, Me4Si) d 16.4 (d, JPC¼6.5 Hz), 61.9 (d, JPC
¼
2
6.0 Hz), 114.8 (d, JPC¼190.0 Hz), 128.9, 129.1, 133.4
(d, 3JPC¼23.7 Hz), 136.1, 147.2 (d, 2JPC¼6.5 Hz); 31P NMR
(81 MHz, CDCl3, 85% H3PO4) d 19.5. Positive ion ESI-
MS: m/z¼274.9, 276.9 (M+H+), 296.9, 298.9 (M+Na+).
HRMS calcd for C12H16ClO3P, 274.0526; found, 274.0522.
2
33.3–30.9 (m), 42.5, 61.3 (d, JPC¼6.8 Hz), 61.4 (d,
1
2JPC¼6.8 Hz), 127.3, 129.3, 130.3 (t, JCD¼18.7 Hz),
3
3
133.0 (d, JPC¼11.3 Hz), 136.0, 141.2 (d, JPC¼10.8 Hz);
31P NMR (81 MHz, CDCl3, 85% H3PO4) d 30.5. Positive
ion ESI-MS: m/z¼341.4 (M+H+). HRMS calcd for
C19H29D2O3P, 340.2136; found, 340.2139.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China 20372041 (20572058) and Beijing
Department of Education (XK100030514).
4.6.5.2. Diethyl 3-deuterium-1-(4-methylphenyl-deu-
terium-methyl)-hept-2-enylphosphonate (13a). H NMR
1
(300 MHz, CDCl3, Me4Si) d 0.78–0.93 (m, 3H), 1.11–1.24
(m, 4H), 1.26–1.32 (m, 6H), 1.91–2.02 (m, 2H), 2.28 (s,
3H), 2.62–2.74 (ddd, 3JHH¼3.1 Hz, 3JHH¼9.3 Hz,
References and notes
3
2JPH¼20.9 Hz, 1H), 3.12 (d, JHH¼9.6 Hz, 1H), 3.11–3.18
3
(m, 1H), 4.06–4.14 (m, 4H), 5.24 (t, JHH¼7.5 Hz,
1. (a) Kaboudin, B.; Nazari, R. Tetrahedron Lett. 2001, 42, 8211–
8213; (b) Kim, D. Y.; Rhie, D. Y. Tetrahedron 1997, 53, 13603–
13608; (c) Schultz, P.; Lerner, R. A. Acc. Chem. Res. 1993, 26,
391–395; (d) Stewart, J. D.; Liotta, L. J.; Benkovic, S. J. Acc.
3JPH¼7.5 Hz, 1H), 6.93–7.02 (m, 4H); 13C NMR (75 MHz,
CDCl3, Me4Si) d 13.9, 16.3–16.6 (m), 21.1, 21.9, 31.3
(d, JPC¼2.9 Hz), 32.3, 34.3 (t, JCD¼17.9 Hz), 43.6
4
1
1
3
´
(d, JPC¼136.3 Hz), 61.8 (d, JPC¼7.5 Hz), 62.3 (d,
3JPC¼7.5 Hz), 123.6 (d, 2JPC¼9.8 Hz), 128.9, 129.1, 135.6,
Chem. Res. 1993, 26, 396–404; (e) Cox, R. J.; Mayo-Martın,
M. B.; Hadfield, A. T. Chem. Commun. 2001, 1710–1711.
2. (a) Han, L.-B.; Tanaka, M. Chem. Lett. 1999, 863–864; (b)
Han, L.-B.; Choi, N.; Tanaka, M. J. Am. Chem. Soc. 1996,
118, 7000–7001; (c) Lai, C.; Xi, C.; Chen, C.; Ma, M.;
Hong, X. Chem. Commun. 2003, 2736–2737.
136.2 (d, JPC¼16.5 Hz), 136.5–135.7 (m); 31P NMR
3
(81 MHz, CDCl3, 85% H3PO4) d 29.9. Positive ion ESI-
MS: m/z¼341.4 (M+H+).
4.7. A procedure for the reaction of Cp2Zr(ClPhCH]
CH2) with chlorophosphate: preparation of diethyl-2-
(4-chlorophenyl)-1,2-zircono-ethylphosphonate
3. (a) Deprele, S.; Montchamp, J.-L. J. Am. Chem. Soc. 2002, 124,
9386–9387; (b) Stockland, R. A., Jr.; Taylor, R. I.; Thompson,
L. E.; Patel, P. B. Org. Lett. 2005, 7, 851–853; (c) Montchamp,
J.-L. J. Organomet. Chem. 2005, 690, 2388–2406.
To a solution of dibutylzirconocene in THF was added
1.0 equiv of 4-chloro-styrene and stirred for 1 h at room tem-
perature. Chlorophosphate (1 mmol, 144.7 mL) was added to
this solution and stirred for 24 h at 0–5 ꢀC (31P NMR yield
51%). 31P NMR (81 MHz, THF, 85% H3PO4) d 49.1 ppm.
4. (a) Shulyupin, M. O.; Francio, G.; Beletskaya, I. P.; Leitnerb,
W. Adv. Synth. Catal. 2005, 347, 667–672; (b) Tayama, O.;
Nakano, A.; Iwahama, T.; Sakaguchi, S.; Ishii, Y. J. Org.
Chem. 2004, 69, 5469–5494; (c) Reichwein, J. F.; Patel,
M. C.; Pagenkopf, B. L. Org. Lett. 2001, 3, 4303–4306; (d)
Mirzaei, F.; Han, L.-B.; Tanaka, M. Tetrahedron Lett. 2001,
42, 297–299; (e) Han, L.-B.; Mirzaei, F.; Zhao, C.-Q.;
Tanaka, M. J. Am. Chem. Soc. 2000, 122, 5407–5408.
5. Zhao, C.-Q.; Han, L.-B.; Tanaka, M. Organometallics 2000, 19,
4196–4198.
6. (a) Negishi, E.; Cederbaum, F. E.; Takahashi, T. Tetrahedron
Lett. 1989, 27, 2829–2832; (b) Takahashi, T.; Swanson,
D. R.; Negishi, E. Chem. Lett. 1987, 623–626.
7. (a) Takahashi, T.; Murakami, M.; Saburi, M.; Uchida, Y.;
Kozwa, K.; Uchida, T.; Sanson, D. R.; Negishi, E. Chem.
Lett. 1989, 761–764; (b) Buchw, S. L.; Buchwald, S. L.;
Waston, B. T. J. Am. Chem. Soc. 1987, 109, 2544–2546; (c)
Negishi, E.; Nguyen, T.; Maye, J. P.; Choueiri, D.; Suzuki,
N.; Takahashi, T. Chem. Lett. 1992, 2367–2370.
4.7.1. Preparation of diethyl 2-(4-chlorophenyl)ethyl-
phosphonate (8c).25 The resulting mixture of diethyl 2-(4-
chlorophenyl)-1,2-zircono-ethylphosphonate was treated
with 3 N HCl and stirred for 1 h. Then it was carried out
in a similar way to that described above to get 140 mg of
the title compound as a colorless liquid (isolated yield
48%). 1H NMR (300 MHz, CDCl3, Me4Si) d 1.25–1.34
(m, 6H), 1.97–2.08 (m, 2H), 2.86–2.92 (m, 2H), 4.07–4.12
(m, 4H), 7.12–7.32 (m, 4H); 13C NMR (75 MHz, CDCl3,
3
1
Me4Si) d 6.5 (d, JPC¼6.2 Hz), 27.5 (d, JPC¼139.1 Hz),
2
3
28.0 (d, JPC¼4.4 Hz), 61.7 (d, JPC¼6.8 Hz), 128.7,
129.5, 132.2, 140.5 (d, JPC¼18.3 Hz); 31P NMR
3
(81 MHz, CDCl3, 85% H3PO4) d 32.4. Positive ion ESI-
MS: m/z¼277.1, 279.0 (M+H+). HRMS calcd for
C12H18ClO3P, 276.0682; found, 276.0685.
8. Alt, H. G.; Denner, C. E.; Thewalt, U.; Rausch, M. D.
J. Organomet. Chem. 1988, 356, C83–C85.
9. Swanson, D. R.; Negishi, E. Organometallics 1991, 10, 825–
826.
10. Swanson, D. R.; Rousset, C. J.; Negishi, E.; Takahashi, T.; Seki,
T.; Saburi, M.; Uchida, Y. J. Org. Chem. 1989, 54, 3521–3523.
4.7.2. Preparation of diethyl (E)-2-(4-chlorophenyl)
ethenylphosphonate (10c).26 The resulting mixture of
diethyl 2-(4-chlorophenyl)-1,2-zircono-ethylphosphonate

6302
C. Lai et al. / Tetrahedron 62 (2006) 6295–6302
11. Suzuki, N.; Rousset, C. J.; Aoyagi, K.; Kotora, M.; Takahashi,
T. J. Organomet. Chem. 1994, 473, 117–128.
20. Balczewski, P.; Pietrzykowski, W. M. Tetrahedron 1997, 53,
7291–7304.
12. Xi, C.; Ma, M.; Li, X. Chem. Commun. 2001, 2554–2555.
13. Takahashi, T.; Seki, T.; Nitto, Y.; Saburi, M.; Rousset, C. J.;
Negishi, E. J. Am. Chem. Soc. 1991, 113, 6266–6268.
14. (a) Lai, C.; Xi, C.; Feng, Y. Phosphorus Sulfur Silicon Relat.
Elem 2004, 179, 449–456; (b) Baldwin, I. C.; Beckett, R. P.;
Williams, J. M. Synthesis 1996, 34–36.
21. Xu, Y. B.; Flavin, M. T.; Xu, Z. Q. J. Org. Chem. 1996, 61,
7697–7701.
22. Kobayashi, Y.; William, A. D. Adv. Synth. Catal. 2004, 346,
1749–1757.
23. Tashtoush, H. I.; Sustmann, R. Chem. Ber. 1993, 126, 1759–
1762.
15. Balczewski, P.; Pietrzykowski, W. M. Tetrahedron 1996, 52,
13681–13694.
16. Binns, M. R.; Haynes, R. K.; Katsifis, A. G.; Schober, P. A.;
Vonwiller, S. C. J. Am. Chem. Soc. 1988, 110, 5411–5423.
17. Lopin, C.; Gouhier, G.; Gautier, A.; Piettre, S. R. J. Org. Chem.
2003, 26, 9916–9923.
18. Balczewski, P.; Mikolajczyk, M. Synthesis 1995, 4, 392–396.
19. Wnuk, S. F.; Bergolla, L. A.; Garcia, P. I. J. Org. Chem. 2002,
67, 3065–3071.
24. (a) Cristau, H. J.; Pirat, J. L.; Drag, M.; Kafarski, P.
Tetrahedron Lett. 2000, 41, 9781–9786; (b) Zhong, P.; Xiong,
Z. X.; Huang, X. Synth. Commun. 2000, 30, 273–278.
25. Brindaban, C.; Guchhait, S. K.; Ghosh, K. J. Org. Chem. 1998,
63, 5250–5251.
26. (a) Sheng, S. R.; Zhou, W.; Liu, X. L.; Song, C. S. Synth.
Commun. 2004, 34, 1011–1016; (b) Yokomatsu, T.;
Yamagishi, T.; Suemune, K.; Yoshida, Y.; Shibuya, S.
Tetrahedron 1998, 54, 767–768.