Efficient catalytic asymmetric synthesis of α-substituted phenyloxyacetyloxy and aroyloxy phosphonates

Article abstract of DOI:10.1016/j.tet.2006.09.011

Optically active α-substituted phenyloxyacetyloxy and aroyloxy phosphonates have been synthesized via catalytic asymmetric hydrogenation of the corresponding prochiral α,β-unsaturated phosphonates using Rh(I)/(R,R)-Me-DuPhos as the catalyst in methanol at

Full text of DOI:10.1016/j.tet.2006.09.011

Tetrahedron 62 (2006) 11207–11217
Efficient catalytic asymmetric synthesis of a-substituted
phenyloxyacetyloxy and aroyloxy phosphonates
Hui Liu,a Yong-Gui Zhou,b Zheng-Kun Yu,b Wen-Jing Xiao,a,
*
Sheng-Hua Liua and Hong-Wu Hea
aKey Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University,
152 Luoyu Road, Wuhan, Hubei 430079, China
bDalian Institute of Chemical Physics, Chinese Academy of Science, 457 Zhongshan Road, Dalian, Liaoning 116023, China
Received 5 July 2006; revised 4 September 2006; accepted 6 September 2006
Available online 28 September 2006
Abstract—Optically active a-substituted phenyloxyacetyloxy and aroyloxy phosphonates have been synthesized via catalytic asymmetric
hydrogenation of the corresponding prochiral a,b-unsaturated phosphonates using Rh(I)/(R,R)-Me-DuPhos as the catalyst in methanol at
18 ꢀC. The asymmetric hydrogenation reaction exhibits excellent enantioselectivity with enantiomeric excesses from 91 to 96%.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
aroyloxy phosphonates, two kinds of important derivatives
of a-hydroxy phosphonates. Recently, we have synthesized
a series of racemic a-substituted phosphonates and exam-
ined their biological activities.14 It has been found that a-
substituted phenyloxyacetyloxy and aroyloxy phosphonates,
forexample, dimethyla-(2,4-dichlorophenoxyacetoxy)ethyl
phosphonate, are good inhibitors of pyruvate dehydroge-
nases and exhibit potent herbicidal activities.14 Considering
the importance of chirality for biologically active molecules,
synthesis of optically active a-substituted phenoxyacetyloxyl
and aroyloxy phosphonates is of great interest. Based on
the pioneering work of Burk and Imamoto,10 we herein
describe the catalytic asymmetric synthesis of a-substituted
phenyloxyacetyloxy and aroyloxy phosphonates via asym-
metric hydrogenation of the corresponding prochiral a,b-
unsaturated phosphonates using Rh(I)/(R,R)-Me-DuPhos
complex as the catalyst.
The biological importance of phosphonates was recognized
over 45 years ago.1 Among them, a-substituted phospho-
nates are particularly important in connection with their
remarkable biological activities. They have been widely
used as enzyme inhibitors,2 antibacterial agents,3 anti-HIV
agents,4 botryticides,5 and haptens for catalytic antibodies.6
For these reasons, the synthesis of a-substituted phospho-
nates and their functionalized derivatives is an important
objective.7 The absolute configuration of a-substituted
phosphonates can affect their biological activity,8 thus stim-
ulating interest in the asymmetric synthesis of these com-
pounds. For example, intensive efforts have been made in
the asymmetric synthesis of optically active a-amino and
a-hydroxy phosphonates in recent years.9 Enantioselective
and catalytic processes are especially attractive. Elegant
examples include enantioselective synthesis of a-hydroxy
and/or a-amino phosphonates via asymmetric hydrogena-
tion,10 asymmetric borane reduction,11 asymmetric dihy-
droxylation and aminohydroxylation,12 and asymmetric
hydrophosphonylation.13
2. Results and discussion
The a-substituted a,b-unsaturated phosphonates are synthe-
sized by a two-step procedure as shown in Scheme 1. The
Arbuzov reaction of acyl chlorides 2 and trialkyl phosphates
1 gave a-keto phosphonates 3, which were then treated with
various aroyl chlorides or substituted phenoxyacetyl chlo-
rides in the presence of Et3N from 0 ꢀC to room temperature
to exclusively afford E-a-substituted a,b-unsaturated phos-
phonates 4a–4w in 56–95% isolated yields.15 To our knowl-
edge, the a,b-unsaturated phosphonates 4a–4w are novel
and first synthesized.
Although numerous methods are available for the asymmet-
ric synthesis of a-hydroxy and a-amino phosphonates, there
are no reports concerning the straightforward route to asym-
metric synthesis of a-substituted phenyloxyacetyloxy and
Keywords: Asymmetric catalysis; Chirality; Phosphonate; Hydrogenation.
* Corresponding author. Tel./fax: +86 27 67862041; e-mail: wxiao@mail.
ccnu.edu.cn
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.011

11208
H. Liu et al. / Tetrahedron 62 (2006) 11207–11217
O
P
(R,R)-Me-DuPhos (Table 1, entries 1, 3, and 4). Compared
to other bidentate phosphine, (R)-BINAP is almost ineffec-
tive (Table 1, entry 2), which is consistent with other asym-
metric hydrogenations of enol derivatives.16 Hydrogenation
of 4a with Rh-(R)-MA-Me catalyst under analogous reaction
conditions resulted in only poor conversion (Table 1, entry
5). With dichloromethane as the solvent and under higher
pressure of H2, the chiral monodentate ligand, (R)-MA-
Me, can be used for this reaction, but it is not as effective
as (R,R)-Me-DuPhos in terms of either activity or stereo-
selectivity (Table 1, entry 6). The method to generate the
chiral catalyst has no obvious effects on either reactivity or
enantioselectivity, and the reaction gave almost identical re-
sults, irrespective of the use of the in situ generated catalyst
or commercially available one (Table 1, entries 1 vs 7). Note
that [Rh(COD)2]BF4/(R,R)-Me-DuPhos and [(COD)Rh-
(S,S)-Me-DuPhos]OTf constitute the same stereochemical
environment, although the respective absolute configura-
tions are different (Table 1, entries 1 and 7).
O
P
R1O
R1O
R1O
R1O
R2
Cl
R2
a
b
(R1O)3P
R2
Ar
O n
+
O
O
O
O
4a-4w
1
2
3
R1=Me or Et; R2=H or Me; Ar=phenyl, substituted phenyl, thiophenyl, or
furfuryl; n=0 or 1.
(a) 0 °C-rt, 12 h. (b) Substituted aroyl or phenoxyacetyl chlorides, Et3N,
THF, 0 °C-rt, 3 h.
Scheme 1.
In the search for an efficient catalyst, a variety of chiral
bisphosphine ligands and a monodentate phosphorus ligand
have been screened by using [Rh(COD)2]BF4 as the catalyst
precursor and the results are summarized in Table 1. With di-
methyl a-(2,4-dichlorophenoxyacetoxy) vinyl phosphonate
4a as a representative substrate, the asymmetric hydrogena-
tion was initially effected in methanol with hydrogen
pressure of 4 atm using the in situ generated chiral Rh(I)-
complexes (Table 1, entries 1–5). The ligands employed
played an important role in this transformation, with Me-
DuPhos being an excellent ligand (Table 1, entry 1). Under
these reaction conditions, the asymmetric hydrogenation
could be completed within 12 h at 18 ꢀC with excellent
conversion (>95%) and enantiomeric excess (ee, 94%).
Although (R)-syn-Phos and (4S,5S)-DIOP were also effec-
tive as added ligands for this rhodium(I)-catalyzed hydro-
genation, the results were generally inferior to those of
Table 2 summarizes some results of the effect of varying the
reaction conditions. Using the [Rh(COD)2]BF4/(R,R)-Me-
DuPhos catalyst system, we observed that the enantioselec-
tivity of the reaction depended on the solvents employed
(Table 2). Although the catalytic hydrogenation went to
completion in both CH2Cl2 and THF, the reaction led to 78
and 88% ee, respectively (Table 2, entries 2 and 3). Almost
no reaction was observed in toluene probably due to the little
solubility of the catalyst in toluene (Table 2, entry 4).
Table 1. Ligands screening on the asymmetric hydrogenation
O
P
O
P
MeO
MeO
MeO
MeO
Cl
Cl
Cl
Cl
*
O
[Rh(COD)2]BF4/L*
S/C=100, H2, 12 h
O
O
O
O
O
4a
5a
O
O
O
PPh2
PPh2
PPh2
PPh2
P
P
O
(R,R)-Me-DuPhos
(R)-BINAP
(R)-Syn-Phos
Ph
O
O
O
O
P
O
Ph2P
Ph2P
O
O
O
Me
Ph
O
(4S,5S)-DIOP
(R)-MA-Me
Conv.a (%)
Entry
Pressure (atm)
Solvent
Ligand
eeb (%)
1
2
3
4
5
6
7
4
4
4
4
4
MeOH
MeOH
MeOH
MeOH
MeOH
CH2Cl2
MeOH
(R,R)-Me-DuPhos
(R)-BINAP
(R)-syn-Phos
(4S,5S)-DIOP
(R)-MA-Me
>95
<5
50
59
<5
64
94
nd
32
16
nd
36
ꢁ94
10
4
(R)-MA-Me
(S,S)-Me-DuPhosc
>95
Conversions were determined by 1H NMR.
Enantiomeric excesses were determined by chiral HPLC on a Daicel Chiralcel OJ-H column.
Commercially available [(COD)Rh-(S,S)-Me-DuPhos]OTf as the catalyst.
a
b
c

H. Liu et al. / Tetrahedron 62 (2006) 11207–11217
Table 2. Investigation of reaction conditions on the asymmetric hydrogenation
11209
O
P
O
P
MeO
MeO
MeO
MeO
Cl
Cl
Cl
Cl
[Rh(COD)2]BF4/(R,R)-Me-DuPhos
O
O
O
S/C=100, H2, 12 h
O
O
O
5a
4a
Entry
Pressure (atm)
Temp (ꢀC)
Solvent
Conv.a (%)
eeb (%)
1
2
3
4
5
6
7
8c
4
4
4
4
4
1.3
10
4
18
18
18
18
50
18
18
18
MeOH
CH2Cl2
THF
Toluene
MeOH
MeOH
MeOH
MeOH
>95
>95
>95
<5
>95
>95
>95
15
94
78
88
nd
94
94
94
93
Conversions were determined by 1H NMR.
Enantiomeric excesses were determined by chiral HPLC on a Daicel Chiralcel OJ-H column.
S/C¼500:1.
a
b
c
Table 3. Results of the catalytic asymmetric hydrogenation of various
a-substituted phenyloxyacetyloxy-a,b-unsaturated phosphonates
Changing the hydrogen pressure to 1.3 or 10 atm resulted in
identical results (Table 2, entries 6 and 7 vs 1). Increasing the
reaction temperature from 18 to 50 ꢀC did not affect the re-
action (Table 2, entries 1 and 5). Reducing the catalyst load-
ing to S/C¼500:1 resulted in much lower conversion, only
15%. However, it did not decrease the ee value very much
(Table 2, entry 8).
O
P
O
P
R1O
R1O
R1O
R1O
Rh(I)/(R,R)-Me-DuPhos
R3
R3
MeOH, S/C=100,
O
O
O
O
H
2 (4 atm), 18 °C, 12 h
O
O
4a-4i
5a-5i
Entry
Product
Conv.a (%) eeb (%) Config.c
The asymmetric hydrogenation of a series of substituted
a,b-unsaturated phosphonates was then performed using
1 mol % of in situ generated Rh(I)-catalyst in MeOH at
4 atm of H2 for 12 h at 18 ꢀC and the results are summarized
in Tables 3 and 4. This rhodium-catalyzed hydrogenation
exhibits broad substrate scope and excellent levels of enan-
tioselectivity from 91 to 96% ee.
O
P
MeO
Cl
O
Cl
Cl
MeO
O
1
>95
>95
>95
>95
>95
>95
94
96
93
93
95
91
S-(+)
O
5a
O
P
EtO
EtO
Cl
O
Our main objective was to develop a practical route to a di-
verse range of optically active a-substituted ethyl phospho-
nates 5a–5u. Table 3 shows the results of the synthesis of
chiral aroyloxyacetyloxylethyl phosphonates via asymmet-
ric hydrogenation. Substrates with O,O-dimethyl or O,O-
diethyl were hydrogenated with excellent enantiomeric
excesses ranging from 91 to 96% ee. The hydrogenation
reaction took place very well regardless of various electron-
withdrawing or electron-donating substituent on the differ-
ent positions of the aromatic ring. The biological study
showed that the hydrogenation product, for example, (S)-di-
ethyl a-(2,4-dichlorophenoxyacetoxy) ethyl phosphonate 5b
exhibited potent herbicidal activity.
O
2
3
4
5
6
(S)-(+)
(S)-(+)
(S)-(+)
(S)-(+)
O
5b
O
P
MeO
MeO
O
O
O
O
5c
O
P
MeO
MeO
Cl
O
O
5d
Burk and co-workers have demonstrated that the Me-
DuPhos-Rh is capable of hydrogenating enolbenzoates
with some examples.10c In order to examine the diversity
of the substrates, we have synthesized a variety of a,a-disub-
stituted- and a,a,b-trisubstituted vinyl phosphonates with
different substituents on the benzene ring as well as some
substrates with O- or S-heterocycles and subjected them
to our standard reaction conditions. It was found that
the substituted benzoxyl alkyl phosphonates 5j–5p with
electron-donating or electron-withdrawing group on the
aromatic ring were also obtained with excellent ee values
(Table 4, entries 1–7). The asymmetric hydrogenation of
heterocyclic substrates went smoothly to afford the expected
O
P
MeO
MeO
Cl
O
O
O
O
5e
O
P
MeO
MeO
Me
O
(S)-(+)
O
5f
(continued)

11210
H. Liu et al. / Tetrahedron 62 (2006) 11207–11217
Table 3. (continued)
Table 4. (continued)
Entry
Product
Conv.a (%) eeb (%) Config.c
Entry
Product
Conv.a (%)
eeb (%)
Config.c
O
P
O
P
MeO
MeO
MeO
MeO
OMe
Cl
Cl
O
O
6
>95
91
(S)-(+)
7
91
95
(S)-(+)
O
O
O
5o
5g
O
P
O
EtO
EtO
MeO
P
F
MeO
O
O
7
>95
>95
>95
92
96
95
(S)-(+)
(S)-(ꢁ)
(S)-(ꢁ)
8
>95
>95
94
92
(S)-(+)
(S)-(+)
O
O
O
5p
5h
O
P
O
P
CF3
MeO
MeO
MeO
O
MeO
9
O
O
O
8
O
O
O
5q
S
5i
Conversions were determined by 1H NMR.
Enantiomeric excesses were determined by chiral HPLC on a Daicel
Chiralcel OJ-H or AS-H column.
Configurations were assigned on the basis of correlation between HPLC
elution order, optical rotation, and catalyst configuration relative to the
known compound 6a.
a
O
P
b
MeO
MeO
c
9
O
5r
S
O
Table 4. Results of the catalytic asymmetric hydrogenation of various
a-substituted aroyloxy-a,b-unsaturated phosphonates
EtO
EtO
P
O
O
P
O
P
10
>95
>95
95
94
(S)-(ꢁ)
(S)-(+)
R1O
R1O
R1O
R1O
R2
Ar
R2
Ar
O
Rh(I)/(R,R)-Me-DuPhos
5s
O
O
MeOH, S/C=100,
2 (4 atm), 18 °C, 12 h
H
O
P
O
O
MeO
MeO
5j-5t
eeb (%)
4j-4t
S
11d
O
Entry
Product
Conv.a (%)
Config.c
O
5t
O
P
MeO
Me
Conversions were determined by 1H NMR.
Enantiomeric excesses were determined by chiral HPLC on a Daicel
Chiralcel OJ-H column.
Configurations were assigned on the basis of correlation between HPLC
elution order, optical rotation, and catalyst configuration relative to the
known compound 6a.
a
MeO
b
O
1
>95
95
(S)-(ꢁ)
(S)-(ꢁ)
(S)-(+)
(S)-(ꢁ)
(S)-(ꢁ)
c
O
5j
O
P
d
Under 10 atm H2 pressure.
EtO
EtO
Me
O
2
3
4
5
>95
95
94
95
96
products 5q–5t in great conversions with excellent enantio-
selectivities (Table 4, entries 8–11). Although the strong thio-
philicity of transition metals might make the catalytic
reaction ineffective,17 the catalytic hydrogenation of 4r,
4s, and 4t was carried out in more than 95% conversions
under mild conditions, respectively. a,a,b-Trisubstituted-
a,b-unsaturated phosphonates 4t were only partially hydro-
genated under the optimized reaction conditions after 12 h,
and this is perhaps due to a combination of steric or
electronic effect.10a However, with higher H2 pressure
(10 atm), 4t goes to completion smoothly (Table 4, entry 11).
O
5k
O
P
MeO
MeO
Me
O
O
O
>95
O
5l
O
P
MeO
MeO
Cl
>95
O
5m
In the case of 4u and 4v, the reaction gave similarly high
conversion but a slightly low enantioselectivity (89 and
91% ee, respectively, Scheme 2).
O
P
EtO
EtO
Cl
>95
The a-substituted phenyloxyacetyloxy and aroyloxy phos-
phonates 5 can be simply deprotected using K2CO3 in MeOH
at room temperature for 2 h to afford the corresponding
O
5n
(continued)

H. Liu et al. / Tetrahedron 62 (2006) 11207–11217
11211
O
P
O
P
20 mL of THF, and this solution was then added slowly to the
reaction mixtures. After stirred for 45 min, the reaction mix-
ture was warmed up to room temperature and stirred for
another 3 h. The reaction mixture was diluted with EtOAc
(200 mL), which was washed with saturated NaHCO3
(100 mLꢂ3), brine (75 mL), and then dried with MgSO4.
The solvent was removed in vacuo to give yellow oil, which
was purified on silica gel (EtOAc:petroleum ether¼1:1) to
give 5.93 g of 4a as white solid in 59% isolated yield.
MeO
MeO
MeO
MeO
Rh(I)/(R,R)-Me-DuPhos
O
O
MeOH, S/C=100,
2 (4 atm), 18 °C, 12 h
O
O
H
O
O
5u
4u
conv.: >95%; ee: 89%
O
O
P
MeO
MeO
MeO
P
Rh(I)/(R,R)-Me-DuPhos
MeO
MeOH, S/C=100,
2 (4 atm), 18 °C, 12 h
O
O
H
4.1.1. O,O-Dimethyl a-(2,4-dichlorophenoxyacetoxy)
vinyl phosphonate (4a). White solid; yield 59%; mp 78–
80 ꢀC; IR (KBr) 1799, 1636, 1587, 1487, 1252, 1144,
O
O
4v
5v
conv.: >95%; ee: 91%
1
1024, 814, 800 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.41
(d, 1H, J¼2.4 Hz), 7.20 (dd, 1H, J¼8.8 and 2.4 Hz), 6.86
(d, 1H, J¼8.8 Hz), 6.11 (dd, 1H, J¼6.8 and 2.4 Hz), 5.86
(dd, 1H, J¼34.4 and 2.4 Hz), 4.86 (s, 2H), 3.76 (d, 6H,
J¼11.2 Hz); 13C NMR (100 MHz, CDCl3) d 53.2, 53.3,
65.9, 114.3, 114.9, 122.2, 122.5, 124.3, 127.5, 127.7,
130.5, 143.3, 145.6, 152.2, 166.0, 166.1; 31P NMR
(162 MHz, CDCl3) d 9.70; MS (EI) m/z 354 (M+ꢁ1), 355
(M+), 357 (M++2). Anal. Calcd for C12H13Cl2O6P: C,
40.59; H, 3.69. Found: C, 40.38; H, 3.76.
Scheme 2.
a-hydroxy phosphonates 6. In order to determine the
absolute configuration of the hydrogenation products, 5a
was converted to the previously reported compound 6a, as
shown in Scheme 3. The [a]D value of 6a is the same as
the one reported in the literature,17 which indicates that the
absolute configuration of the hydrogenation products is S
configuration.
4.1.2. Diethyl a-(2,4-dichlorophenoxyacetoxy) vinyl
phosphonate (4b). Pale yellow liquid; yield 75%; IR
(KBr) 2984, 1784, 1630, 1585, 1480, 1263, 1161, 1022,
O
P
MeO
MeO
O
P
Cl
Cl
K2CO3, MeOH
MeO
MeO
O
1
801 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.41 (d, 1H, J¼
25 °C, 2 h
O
OH
O
2.4 Hz), 7.19 (dd, 1H, J¼8.8 and 2.4 Hz), 6.86 (d, 1H, J¼
8.8 Hz), 6.10 (dd, 1H, J¼6.8 and 2.4 Hz), 5.81 (dd, 1H,
J¼34.4 and 2.4 Hz), 4.85 (s, 2H), 4.17–4.09 (m, 4H), 1.33
(t, 6H, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3) d 16.0,
16.1, 57.7, 66.0, 115.0, 121.4, 121.6, 124.4, 127.5, 127.7,
130.5, 144.6, 146.8, 152.3, 166.1; 31P NMR (162 MHz,
CDCl3) d 6.75; MS (EI) m/z 382 (M+ꢁ1), 383 (M+), 385
(M++2). Anal. Calcd for C14H17Cl2O6P: C, 43.88; H, 4.47.
Found: C, 43.48; H, 4.76.
5a
6a
[a]14D= +5.4 (c 0.5, acetone)
Scheme 3.
3. Conclusion
In summary, we have synthesized a series of optically active
phenoxyacetyloxyl and aroyloxy phosphonates in high
enantiomeric purity via catalytic asymmetric hydrogenation
using Rh(I)/(R,R)-Me-DuPhos as the catalytic system in
methanol and most of the target compounds including their
precursors are novel. The methodology described herein
represents one of the most straightforward routes to these
compounds.
4.1.3. Dimethyl a-phenoxyacetoxy vinyl phosphonate
(4c). Little yellow solid; yield 68%; mp 57–59 ꢀC; IR
(KBr) 2969, 1778, 1630, 1599, 1589, 1492, 1445, 1378,
1260, 1161, 1017, 946, 840, 797, 755, 695, 586,
532 cmꢁ1 1H NMR (400 MHz, CDCl3) d 7.32 (t, 2H,
;
J¼7.8 Hz), 7.02 (t, 1H, J¼7.2 Hz), 6.94 (d, 2H,
J¼8.0 Hz), 6.13 (dd, 1H, J¼10.8 and 2.2 Hz), 5.85 (dd,
1H, J¼34.6 and 2.2 Hz), 4.80 (s, 2H), 3.76 (d, 6H,
J¼11.2 Hz); 13C NMR (100 MHz, CDCl3) d 53.45, 53.51,
65.1, 114.8, 122.2, 122.4, 122.6, 129.8, 145.6, 157.6,
166.8; 31P NMR (162 MHz, CDCl3) d 10.16; MS (EI) m/z
286 (M+), 287 (M++1). Anal. Calcd for C12H15O6P: C,
50.36; H, 5.28. Found: C, 50.12; H, 5.35.
4. Experimental
4.1. General procedure for the preparation of a,b-
unsaturated phosphonates (the preparation of 4a
is representative)
Acetyl chloride (2.5 mL, 35 mmol) was cooled to 0 ꢀC in an
oven-dried flask fitted with an addition funnel. Trimethyl
phosphite (5 mL, 42 mmol) was added dropwise. A balloon
was used to compensate for the released methyl chloride.
When the addition was complete, the reaction was warmed
to room temperature and stirred overnight. The mixture
was concentrated under vacuum to remove volatile impuri-
ties and then the crude material was taken directly to next
step. THF (40 mL) and 2,4-dichlorophenoxy acetyl chloride
(5 mL, 28.2 mmol) were added to the crude product, and the
system was chilled to 0 ꢀC. Et3N (4.5 mL) was dissolved in
4.1.4. Dimethyl a-(2-chlorophenoxyacetoxy) vinyl phos-
phonate (4d). Colorless liquid; yield 64%; IR (KBr) 2958,
1785, 1589, 1485, 1449, 1258, 1197, 1084, 1043 cmꢁ1; 1H
NMR (400 MHz, CDCl3) d 7.40 (dd, 1H, J¼8.0 and
1.6 Hz), 7.23 (t, 1H, J¼1.2 Hz), 6.98 (t, 1H, J¼1.6 Hz),
6.91 (dd, 1H, J¼4.0 and 1.2 Hz), 6.12 (dd, 1H, J¼11.0
and 2.4 Hz), 5.86 (dd, 1H, J¼34.8 and 2.4 Hz), 4.88 (s,
2H), 3.77–3.72 (m, 6H); 13C NMR (100 MHz, CDCl3)
d 53.50, 53.51, 65.9, 114.1, 112.4, 122.6, 123.1, 123.5,
127.9, 130.8, 143.4, 145.6, 153.3, 166.2; 31P NMR
(162 MHz, CDCl3) d 10.08; MS (EI) m/z 320 (M+ꢁ1), 321

11212
H. Liu et al. / Tetrahedron 62 (2006) 11207–11217
(M+), 322 (M++1). Anal. Calcd for C12H14ClO6P: C, 44.95;
H, 4.40. Found: C, 44.75; H, 4.40.
125.2, 130.4, 132.0, 132.3, 143.4, 145.6, 157.7, 166.28,
166.30; 31P NMR (162 MHz, CDCl3) d 10.04; MS (EI)
m/z 354 (M+), 355 (M++1). Anal. Calcd for C13H14F3O6P:
C, 44.08; H, 3.98. Found: C, 44.19; H, 4.05.
4.1.5. Dimethyl a-(4-chlorophenoxyacetoxy) vinyl phos-
phonate (4e). Little yellow solid; yield 80%; mp 32–
34 ꢀC; IR (KBr) 2957, 1784, 1596, 1493, 1446, 1266,
1151, 1027, 834, 801, 640, 509 cmꢁ1; 1H NMR (400 MHz,
CDCl3) d 7.26 (d, 2H, J¼11.2 Hz), 6.87 (d, 2H,
J¼11.2 Hz), 6.11 (dd, 1H, J¼10.6 and 2.4 Hz), 5.85 (dd,
1H, J¼34.6 and 2.4 Hz), 4.77 (s, 2H), 3.77 (d, 6H,
J¼11.2 Hz); 13C NMR (100 MHz, CDCl3) d 53.3, 53.4,
65.0, 115.99, 122.2, 122.4, 126.9, 129.3, 129.4, 143.0,
156.0, 166.3; 31P NMR (162 MHz, CDCl3) d 9.12; MS
(EI) m/z 320 (M+). Anal. Calcd for C12H14ClO6P: C,
44.95; H, 4.40. Found: C, 44.60; H, 4.74.
4.1.10. Dimethyl a-(4-methylbenzoxy) vinyl phosphonate
(4j). Pale yellow liquid; yield 87%; IR (KBr) 2956, 2854,
1739, 1612, 1578, 1457, 1265, 1176, 1025, 836, 801, 748,
686 cmꢁ1 1H NMR (400 MHz, CDCl3) d 7.98 (d, 2H,
;
J¼8.4 Hz), 7.28 (d, 2H, J¼8.0 Hz), 6.18 (dd, 1H, J¼10.8
and 2.2 Hz), 5.92 (dd, 1H, J¼34.2 and 2.2 Hz), 3.82 (d,
6H, J¼11.2 Hz), 2.44 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 21.6, 53.18, 53.23, 121.9, 122.2, 126.0,
129.4, 130.3, 144.0, 144.9, 146.3, 164.3; 31P NMR
(162 MHz, CDCl3) d 10.33; MS (EI) m/z 270 (M+). Anal.
Calcd for C12H15O5P: C, 53.34; H, 5.60. Found: C, 53.49;
H, 5.44.
4.1.6. Dimethyl a-(4-methylphenoxyacetoxy) vinyl phos-
phonate (4f). Little yellow liquid; yield 87%; IR (KBr)
2958, 1786, 1613, 1512, 1445, 1250, 1149, 1032 cmꢁ1; 1H
NMR (400 MHz, CDCl3) d 7.10 (d, 2H, J¼8.4 Hz), 6.83
(d, 2H, J¼8.4 Hz), 6.12 (dd, 1H, J¼11.0 and 2.2 Hz),
5.85 (dd, 1H, J¼36.6 and 2.2 Hz), 4.76 (s, 2H,), 3.78–3.75
(m, 6H); 13C NMR (100 MHz, CDCl3) d 20.5, 53.37,
53.43, 65.2, 114.4, 114.6, 122.3, 122.6, 130.1, 131.4,
143.3, 145.6, 145.6, 155.5, 166.9; 31P NMR (162 MHz,
CDCl3) d 10.19; MS (EI) m/z 300 (M+), 301 (M++1).
Anal. Calcd for C13H17O6P: C, 52.00; H, 5.71. Found: C,
52.44; H, 5.48.
4.1.11. Diethyl a-(4-methylbenzoxy) vinyl phosphonate
(4k). Pale yellow liquid; yield 78%; IR (KBr) 2984, 1740,
1611, 1577, 1478, 1393, 1267, 1198, 1019, 975, 798, 748,
687 cmꢁ1 1H NMR (400 MHz, CDCl3) d 7.98 (d, 2H,
;
J¼8.4 Hz), 7.28 (d, 2H, J¼8.4 Hz), 6.17 (dd, 1H, J¼11.2
and 2.0 Hz), 5.90 (dd, 1H, J¼35.2 and 2.0 Hz), 4.22–4.16
(m, 4H), 2.44 (s, 3H), 1.34 (t, 6H, J¼6.8 Hz); 13C NMR
(100 MHz, CDCl3) d 16.36, 16.42, 21.90, 63.1, 63.2,
121.4, 121.7, 126.1, 129.5, 130.3, 144.9, 147.2, 164.2; 31P
NMR (162 MHz, CDCl3) d 7.46; MS (EI) m/z 299 (M++1).
Anal. Calcd for C14H19ClO5P: C, 56.37; H, 6.42. Found:
C, 56.56; H, 6.15.
4.1.7. Dimethyl a-(4-methoxyphenoxyacetoxy) vinyl
phosphonate (4g). Yellow liquid; yield 75%; IR (KBr)
2958, 1762, 1507, 1458, 1202, 1034 cmꢁ1
;
1H NMR
4.1.12. (E)-Dimethyl a-(4-methylbenzoxy) propenyl
phosphonate (4l). White solid; yield 88%; mp 36–39 ꢀC;
IR (KBr) 2960, 2856, 1737, 1662, 1612, 1446, 1262, 1179,
(400 MHz, CDCl3) d 6.90–6.83 (m, 4H), 6.12 (dd, 1H,
J¼10.8 and 2.4 Hz), 5.84 (dd, 1H, J¼34.6 and 2.2 Hz),
4.74 (s, 2H), 3.80–3.74 (m, 9H); 13C NMR (100 MHz,
CDCl3) d 53.2, 53.3, 53.6, 65.8, 114.6, 115.8, 122.1,
122.4, 143.2, 145.4, 151.6, 154.6, 166.6; 31P NMR
(162 MHz, CDCl3) d 9.16; MS (EI) m/z 316 (M+). Anal.
Calcd for C13H17O7P: C, 49.37; H, 5.42. Found: C, 49.02;
H, 5.47.
1
1017, 806, 752, 688 cmꢁ1; H NMR (400 MHz, CDCl3)
d 8.01 (d, 2H, J¼8.0 Hz), 7.29 (d, 2H, J¼8.4 Hz), 6.71–
6.63 (m, 1H), 3.78 (d, 6H, J¼11.2 Hz), 2.44 (s, 3H), 1.74
(dd, 3H, J¼6.8 and 2.8 Hz); 13C NMR (100 MHz, CDCl3)
d 12.1, 12.3, 21.8, 53.15, 53.20, 125.8, 129.4, 130.3, 135.1,
135.4, 139.2, 141.8, 144.8, 163.5; 31P NMR (162 MHz,
CDCl3) d 11.72; MS (EI) m/z 284 (M+). Anal. Calcd for
C13H17O5P: C, 54.93; H, 6.03. Found: C, 54.84; H, 5.84.
4.1.8. Dimethyl a-(4-fluorophenoxyacetoxy) vinyl phos-
phonate (4h). Yellow liquid; yield 79%; IR (KBr) 2960,
1785, 1507, 1443, 1204, 1033, 831 cmꢁ1
;
1H NMR
4.1.13. Dimethyl a-(4-chlorobenzoxy) vinyl phosphonate
(4m). Colorless liquid; yield 95%; IR (KBr) 2959, 1735,
(400 MHz, CDCl3) d 7.00 (t, 2H, J¼7.6 Hz), 6.91–6.88
(m, 2H), 6.11 (dd, 1H, J¼10.6 and 2.4 Hz), 5.85 (dd,
1H, J¼34.4 and 2.4 Hz), 4.76 (s, 2H), 3.77 (d, 6H,
J¼11.2 Hz); 13C NMR (100 MHz, CDCl3) d 53.4, 53.5,
65.7, 116.0, 116.1, 116.3, 122.3, 122.5, 143.4, 145.6,
153.8, 156.9, 159.3, 166.7; 31P NMR (162 MHz, CDCl3)
d 10.14; MS (EI) m/z 304 (M+), 305 (M++1). Anal. Calcd
for C12H14FO6P: C, 47.38; H, 4.64. Found: C, 47.49; H,
4.60.
1633, 1595, 1402, 1263, 1191, 1013, 834, 751, 680 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 8.03 (dd, 2H, J¼6.8 and
2.0 Hz), 7.47 (dd, 2H, J¼6.8 and 2.0 Hz), 6.18 (dd, 1H,
J¼10.8 and 2.0 Hz), 5.93 (dd, 1H, J¼34.2 and 2.4 Hz),
3.82 (d, 6H, J¼11.2 Hz); 13C NMR (100 MHz, CDCl3)
d 53.25, 53.30, 122.1, 122.3, 127.2, 128.8, 129.1, 131.5,
131.7, 140.6, 144.0, 146.2, 163.5; 31P NMR (162 MHz,
CDCl3) d 10.32; MS (EI) m/z 290 (M+ꢁ1), 291 (M+).
Anal. Calcd for C11H12ClO5P: C, 45.46; H, 4.16. Found:
C, 45.48; H, 4.13.
4.1.9. Dimethyl a-(3-trifluoromethylphenoxyacetoxy)
vinyl phosphonate (4i). Little yellow liquid; yield 62%;
IR (KBr) 2962, 2859, 1757, 1594, 1494, 1457, 1331, 1170,
4.1.14. Diethyl a-(4-chlorobenzoxy) vinyl phosphonate
(4n). Colorless liquid; yield 82%; IR (KBr) 2984, 1743,
1633, 1593, 1488, 1401, 1264, 1195, 1016, 850, 754,
1
1127, 1066 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.42 (t,
1H, J¼8.0 Hz), 7.30–7.28 (m, 1H), 7.16–7.12 (m, 2H),
6.13 (dd, 1H, J¼11.2 and 2.4 Hz), 5.85 (dd, 1H, J¼34.4
and 2.4 Hz), 4.84 (s, 2H), 3.76 (d, 6H, J¼11.2 Hz); 13C
NMR (100 MHz, CDCl3) d 53.4, 53.5, 65.1, 111.69,
116.72, 118.3, 118.91, 118.95, 119.8, 122.4, 122.5, 122.7,
680 cmꢁ1 1H NMR (400 MHz, CDCl3) d 8.03 (d, 2H,
;
J¼8.8 Hz), 7.46 (d, 2H, J¼8.4 Hz), 6.17 (dd, 1H, J¼11.2
and 2.0 Hz), 5.90 (dd, 1H, J¼34.8 and 2.0 Hz), 4.21–4.16
(m, 4H), 1.34 (t, 6H, J¼6.8 Hz); 13C NMR (100 MHz,

H. Liu et al. / Tetrahedron 62 (2006) 11207–11217
11213
CDCl3) d 16.06, 16.13, 62.98, 63.03, 121.3, 121.5, 127.4,
129.1, 131.6, 140.5, 145.0, 147.3, 163.5; 31P NMR
(162 MHz, CDCl3) d 7.36; MS (EI) m/z 319 (M+). Anal.
Calcd for C13H16ClO5P: C, 48.99; H, 5.06. Found: C,
49.04; H, 4.97.
J¼7.2 Hz); 13C NMR (100 MHz, CDCl3) d 16.06, 16.12,
121.5, 121.7, 128.2, 132.1, 134.0, 135.1, 144.8, 147.0,
159.6; 31P NMR (162 MHz, CDCl3) d 7.25; MS (EI) m/z
290 (M+), 291 (M++1). Anal. Calcd for C11H15O5PS: C,
45.52; H, 5.21. Found: C, 45.88; H, 5.16.
4.1.15. (E)-Dimethyl a-(4-chlorobenzoxy) propenyl phos-
phonate (4o). Colorless liquid; yield 86%; IR (KBr) 2956,
1740, 1660, 1593, 1488, 1402, 1260, 1174, 1023, 799,
4.1.20. (E)-Dimethyl a-(2-thiophenecarbonyl oxo) pro-
penyl phosphonate (4t). White solid; yield 92%; mp 84–
85 ꢀC; IR (KBr) 2954, 1737, 1664, 1523, 1414, 1259,
1149, 1011, 801, 752, 740, 541 cmꢁ1; 1H NMR (400 MHz,
CDCl3) d 7.92 (dd, 1H, J¼3.6 and 0.8 Hz), 7.67 (dd, 1H,
J¼4.8 and 1.6 Hz), 7.17 (dd, 1H, J¼4.8 and 4.0 Hz), 6.72–
6.64 (m, 1H), 3.80 (d, 6H, J¼11.2 Hz), 1.77 (dd, 3H,
J¼6.8 and 2.8 Hz); 13C NMR (100 MHz, CDCl3) d 12.1,
12.3, 53.29, 53.34, 128.5, 132.0, 134.2, 135.3, 135.7, 136.0,
137.1, 139.4, 159.3; 31P NMR (162 MHz, CDCl3) d 11.38;
MS (EI) m/z 276 (M+), 277 (M++1). Anal. Calcd for
C10H13O5PS: C, 43.48; H, 4.74. Found: C, 43.60; H, 4.81.
1
754, 682 cmꢁ1; H NMR (400 MHz, CDCl3) d 8.05 (dd,
2H, J¼6.8 and 2.0 Hz), 7.47 (dd, 2H, J¼6.8 and 2.0 Hz),
6.71–6.61 (m, 1H), 3.80 (d, 6H, J¼11.2 Hz), 1.75 (dd, 3H,
J¼6.8 and 2.8 Hz); 13C NMR (100 MHz, CDCl3) d 11.8,
12.0, 52.98, 53.03, 127.1, 129.1, 131.7, 135.1, 135.3, 137.1,
139.4, 140.5, 162.8; 31P NMR (162 MHz, CDCl3) d 11.33;
MS (EI) m/z 305 (M+), 307 (M++2). Anal. Calcd for
C12H14ClO5P: C, 47.31; H, 4.63. Found: C, 47.26; H, 4.73.
4.1.16. (E)-Diethyl a-(4-chlorobenzoxy) propenyl phos-
phonate (4p). White solid; yield 56%; mp 52–55 ꢀC; IR
(KBr) 2992, 1734, 1655, 1593, 1488, 1403, 1256, 1148,
1092, 1009, 976, 801, 751, 545 cmꢁ1; 1H NMR (400 MHz,
CDCl3) d 8.05 (dd, 2H, J¼6.8 and 2.0 Hz), 7.47 (dd, 2H,
J¼6.8 and 2.0 Hz), 6.67–6.63 (m, 1H), 4.19–4.11 (m, 4H),
1.73 (dd, 3H, J¼7.2 and 2.4 Hz), 1.32 (t, 6H, J¼6.8 Hz);
13C NMR (100 MHz, CDCl3) d 12.1, 12.3, 16.28, 16.34,
31.5, 62.7, 127.2, 129.0, 131.6, 134.3, 134.6, 140.3, 162.6;
31P NMR (162 MHz, CDCl3) d 8.44; MS (EI) m/z 332
(M+ꢁ1), 333 (M+), 336 (M++3). Anal. Calcd for
C14H18ClO5P: C, 50.54; H, 5.45. Found: C, 50.28; H, 5.59.
4.1.21. Dimethyl a-(methoxyacetoxy) vinyl phosphonate
(4u). Colorless liquid; yield 80%; IR (KBr) 2959, 1775,
1630, 1456, 1376, 1263 cmꢁ1
;
1H NMR (400 MHz,
CDCl3) d 6.11 (dd, 1H, J¼10.4 and 2.3 Hz), 5.84 (dd, 1H,
J¼34.8 and 2.3 Hz), 4.2 (s, 2H), 3.79 (d, 6H, J¼11.2 Hz),
3.49 (s, 3H); 13C NMR (100 MHz, CDCl3) d 53.4, 53.5,
59.6, 69.5, 122.2, 122.4, 143.4, 145.7, 168.1; 31P NMR
(162 MHz, CDCl3) d 10.11; MS (EI) m/z 224 (M+), 225
(M++1). Anal. Calcd for C7H13O6P: C, 37.51; H, 5.85.
Found: C, 37.32; H, 5.59.
4.1.22. Dimethyl a-(phenyl acetoxy) vinyl phosphonate
(4v). Colorless liquid; yield 68%; IR (KBr) 3032, 2956,
4.1.17. Dimethyl a-(2-furancarbonyl oxo) vinyl phospho-
nate (4q). Colorless liquid; yield 73%; IR (KBr) 2959, 2856,
1
1738, 1225, 1031, 934 cmꢁ1; H NMR (400 MHz, CDCl3)
1750, 1577, 1473, 1394, 1294, 1174, 1031, 884, 837 cmꢁ1
;
d 7.36–7.27 (m, 5H), 6.06 (dd, 1H, J¼11.4 and 2.2 Hz),
5.77 (dd, 1H, J¼35.2 and 2.4 Hz), 3.80–3.61 (m, 8H); 13C
NMR (100 MHz, CDCl3) d 40.9, 53.1, 53.2, 121.7, 122.0,
127.4, 128.6, 129.2, 132.8, 143.6, 145.8, 168.9; 31P NMR
(162 MHz, CDCl3) d 9.59; MS (EI) m/z 270 (M+). Anal.
Calcd for C12H15O5P: C, 53.34; H, 5.60. Found: C, 53.38;
H, 5.66.
1H NMR (400 MHz, CDCl3) d 7.66 (s, 1H), 7.32 (s, 1H),
6.58–6.57 (m, 1H), 6.19 (dd, 1H, J¼11.0 and 2.0 Hz), 5.93
(dd, 1H, J¼34.8 and 2.0 Hz), 3.82 (d, 6H, J¼11.2 Hz); 13C
NMR (100 MHz, CDCl3) d 53.2, 53.3, 112.2, 119.9, 122.1,
122.3, 142.9, 143.1, 145.4, 147.4, 155.6, 154.6, 166.6; 31P
NMR (162 MHz, CDCl3) d 9.29; MS (EI) m/z 247 (M++1),
248 (M++2). Anal. Calcd for C9H11O6P: C, 43.91; H, 4.50.
Found: C, 43.73; H, 4.67.
4.2. Typical procedure for the asymmetric hydrogena-
tion (the preparation of 5a is representative)
4.1.18. Dimethyl a-(2-thiophenecarbonyl oxo) vinyl
phosphonate (4r). Waxy solid; yield 85%; IR (KBr) 2957,
1732, 1630, 1522, 1462, 1415, 1267, 1197, 1027, 837,
In a glove box, the Rh/Me-DuPhos complex was made
in situ by mixing [Rh(COD)2]BF4 (2.0 mg, 0.005 mmol)
and (R,R)-Me-DuPhos (1.7 mg, 0.0055 mmol) in MeOH
(2.0 mL). After the mixture was stirred at room temperature
for 10 min, substrate 4a (178 mg, 0.5 mmol) in MeOH
(2.0 mL) was added by a syringe. The hydrogenation was
performed at room temperature under 4 atm H2 for 12 h.
After carefully releasing the excess hydrogen, the conver-
sion was determined by 1H NMR analysis and it was found
more than 95%. The reaction mixtures were concentrated
and then passed through a silica gel plug using ethyl acetate
and petroleum ether (3:1) as an eluant to give pure product
5a (159 mg, 89% yield). The enantiomeric excess (ee value)
was determined by comparison of the enantiomerically
enriched sample to the racemate on chiral HPLC.
1
793, 740 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.91 (d,
1H, J¼3.2 Hz), 7.67 (d, 1H, J¼4.4 Hz), 7.16 (t, 1H,
J¼4.4 Hz), 6.18 (dd, 1H, J¼11.2 and 2.4 Hz), 5.94 (dd,
1H, J¼34.4 and 2.4 Hz), 3.83 (d, 6H, J¼11.2 Hz); 13C
NMR (100 MHz, CDCl3) d 53.28, 53.33, 121.8, 122.0,
128.0, 131.8, 133.9, 134.0, 134.97, 135.03, 143.7, 146.0,
159.4; 31P NMR (162 MHz, CDCl3) d 9.74; MS (EI) m/z
262 (M+), 263 (M++1). Anal. Calcd for C9H11O5PS: C,
41.22; H, 4.23. Found: C, 41.48; H, 4.26.
4.1.19. Diethyl a-(2-thiophenecarbonyl oxo) vinyl phos-
phonate (4s). Colorless liquid; yield 76%; IR (KBr) 2984,
1732, 1630, 1522, 1477, 1415, 1267, 1194, 1026, 851,
1
795, 740 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.91 (d,
1H, J¼3.6 Hz), 7.66 (d, 1H, J¼4.8 Hz), 7.16 (t, 1H,
J¼4.4 Hz), 6.18 (dd, 1H, J¼10.8 and 2.0 Hz), 5.91 (dd,
1H, J¼34.4 and 2.0 Hz), 4.19 (m, 4H), 1.35 (t, 3H,
4.2.1. (S)-Dimethyl a-(2,4-dichlorophenoxyacetoxy) ethyl
phosphonate (5a). Pale yellow liquid; 94% ee; [a]1D4 +15.2
(c 2.00, CHCl3); IR (KBr) 2957, 1741, 1586, 1476, 1456,

11214
H. Liu et al. / Tetrahedron 62 (2006) 11207–11217
1266, 1178, 1021, 836, 802 cmꢁ1
;
1H NMR (400 MHz,
1.30, CHCl3); IR (KBr) 2958, 1768, 1493, 1247, 1188,
1
CDCl3) d 7.38 (d, 1H, J¼2.4 Hz), 7.16 (dd, 1H, J¼8.8 and
2.4 Hz), 6.77 (d, 1H, J¼8.8 Hz), 5.37 (p, 1H, J¼7.2 Hz),
4.74 (s, 2H), 3.77 (t, 6H, J¼10.4 Hz), 1.49 (dd, 3H,
J¼16.6 and 7.2 Hz); 13C NMR (100 MHz, CDCl3) d 15.0,
53.4, 64.4, 66.1, 114.8, 124.1, 127.2, 127.5, 130.3, 152.2,
167.0; 31P NMR (162 MHz, CDCl3) d 22.46; MS (EI) m/z
356 (M+ꢁ1), 357 (M+), 358 (M++1). Anal. Calcd for
C12H15Cl2O6P: C, 40.36; H, 4.23. Found: C, 40.58; H,
4.34. Enantiomeric excess determination: HPLC, UV
202 nm, Chiralcel OJ-H, 1 mL/min, 10% 2-propanol/90%
hexane, (R) t1¼48.57 min; (S) t2¼55.41 min.
1049, 830 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.25 (dd,
2H, J¼7.0 and 2.0 Hz), 6.84 (dd, 2H, J¼6.8 and 2.4 Hz),
5.40 (p, 1H, J¼8.0 Hz), 4.67 (s, 2H), 3.81–3.76 (m, 6H),
1.51 (dd, 3H, J¼16.8 and 7.2 Hz); 13C NMR (100 MHz,
CDCl3) d 15.1, 53.4, 53.5, 53.6, 64.3, 65.4, 66.0, 116.1,
127.0, 129.6, 156.3, 167.65, 167.72; 31P NMR (162 MHz,
CDCl3) d 22.96; MS (EI) m/z 322 (M+ꢁ1), 323 (M+), 324
(M++1). Anal. Calcd for C12H16ClO6P: C, 44.67; H, 5.00.
Found: C, 44.65; H, 4.95. Enantiomeric excess determina-
tion: HPLC, UV 205 nm, Chiralcel AS-H, 0.5 mL/min,
20% 2-propanol/80% hexane, (S) t1¼20.93 min; (R)
t2¼26.53 min.
4.2.2. (S)-Diethyl a-(2,4-dichlorophenoxyacetoxy) ethyl
phosphonate (5b). Pale yellow liquid; 96% ee; [a]D14
+15.1 (c 3.10, CHCl3); IR (KBr) 2984, 1741, 1478, 1265,
4.2.6. (S)-Dimethyl a-(4-methylphenoxyacetoxy) ethyl
phosphonate (5f). Colorless liquid; 91% ee; [a]1D4 +14.8 (c
1.38, CHCl3); IR (KBr) 2957, 1769, 1512, 1447, 1291,
1191, 1022, 801 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d 7.39 (d, 1H, J¼2.4 Hz), 7.17 (dd, 1H, J¼8.8 and
2.4 Hz), 6.79 (d, 1H, J¼8.8 Hz), 5.36 (p, 1H, J¼7.2 Hz),
4.74 (s, 2H), 4.19–4.09 (m, 4H), 1.49 (dd, 3H, J¼16.4 and
7.2 Hz), 1.31 (q, 6H, J¼8.4 Hz); 13C NMR (100 MHz,
CDCl3) d 15.1, 16.5, 63.0, 65.0, 66.3, 66.7, 114.9,
124.3, 127.7, 130.4, 152.3, 167.2; 31P NMR (162 MHz,
CDCl3) d 19.96; MS (EI) m/z 385 (M+), 387 (M++2), 388
(M++3). Anal. Calcd for C14H19Cl2O6P: C, 43.66; H, 4.97.
Found: C, 43.68; H, 4.77. HPLC, UV 293 nm, Chiralcel
OJ-H, 0.5 mL/min, 10% 2-propanol/90% hexane, (R)
t1¼36.87 min; (S) t2¼43.63 min.
1248, 1178, 1048 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d 7.06 (d, 2H, J¼8.0 Hz), 6.77 (d, 2H, J¼8.0 Hz), 5.38
(p, 1H, J¼7.2 Hz), 4.63 (s, 1H), 3.78–3.71 (m, 6H), 2.26
(s, 3H), 1.50 (dd, 3H, J¼16.8 and 7.2 Hz); 13C NMR
(100 MHz, CDCl3) d 15.1, 20.6, 64.1, 65.4, 65.8, 114.5,
130.1, 131.3, 155.6, 168.1, 168.2; 31P NMR (162 MHz,
CDCl3) d 23.40; MS (EI) m/z 322 (M+ꢁ1), 302 (M+), 303
(M++1). Anal. Calcd for C13H19O6P: C, 51.66; H, 6.34.
Found: C, 51.58; H, 6.25. Enantiomeric excess determina-
tion: HPLC, UV 205 nm, Chiralcel OJ-H, 0.8 mL/min,
20% 2-propanol/80% hexane, (S) t1¼21.60 min; (R)
t2¼27.69 min.
4.2.3. (S)-Dimethyl a-phenoxyacetoxy ethyl phosphonate
(5c). Paleyellow liquid; 93% ee; [a]1D4 +12.9 (c 1.40, CHCl3);
IR (KBr) 2958, 1769, 1600, 1496, 1457, 1249, 1178, 1048,
4.2.7. (S)-Dimethyl a-(4-methoxyphenoxyacetoxy) ethyl
phosphonate (5g). Pale yellow liquid; 95% ee; [a]1D4 +12.2
(c 0.74, CHCl3); IR (KBr) 2958, 1769, 1059, 1446, 1244,
833 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 7.29–7.24
(m, 2H), 6.97 (t, 1H, J¼7.4 Hz), 6.95–6.86 (m, 2H), 5.38
(p, 1H, J¼7.2 Hz), 4.66 (s, 2H), 3.77–3.72 (m, 6H), 1.48
(dd, 3H, J¼16.8 and 7.2 Hz); 13C NMR (100 MHz, CDCl3)
d 15.1, 53.47, 53.53, 64.2, 65.2, 65.9, 114.7, 122.0, 129.7,
157.7, 168.0, 168.1; 31P NMR (162 MHz, CDCl3) d 23.3;
MS (EI) m/z 287 (M+ꢁ1), 287 (M+), 289 (M++1). Anal.
Calcd for C12H17O6P: C, 50.00; H, 5.94. Found: C, 50.35;
H, 5.87. Enantiomeric excess determination: HPLC, UV
205 nm, Chiralcel OJ-H, 0.8 mL/min, 20% 2-propanol/
80% hexane, (S) t1¼22.70 min; (R) t2¼26.16 min.
1183, 1032, 831 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d 6.87–6.82 (m, 4H), 5.41 (p, 1H, J¼7.2 Hz), 4.64 (s, 1H),
3.81–3.77 (m, 6H), 1.51 (dd, 3H, J¼16.8 and 7.2 Hz); 13C
NMR (100 MHz, CDCl3) d 15.2, 53.56, 53.62, 55.8, 64.2,
65.9, 66.2, 114.8, 116.0, 152.0, 154.8, 168.4; 31P NMR
(162 MHz, CDCl3) d 23.41; MS (EI) m/z 318 (M+ꢁ1),
319 (M+). Anal. Calcd for C13H19O7P: C, 49.06; H, 6.02.
Found: C, 48.66; H, 5.78. Enantiomeric excess determina-
tion: HPLC, UV 205 nm, Chiralcel AS-H, 0.7 mL/min,
40% 2-propanol/60% hexane, (S) t1¼13.93 min; (R)
t2¼20.14 min.
4.2.4. (S)-Dimethyl a-(2-chlorophenoxyacetoxy) ethyl
phosphonate (5d). Yellow liquid; 93% ee; [a]1D4 +13.1 (c
1.20, CHCl3); IR (KBr) 2958, 1769, 1589, 1485, 1449,
4.2.8. (S)-Dimethyl a-(4-fluorophenoxyacetoxy) ethyl
phosphonate (5h). Pale yellow liquid; 94% ee; [a]D14
+13.3 (c 1.24, CHCl3); IR (KBr) 2959, 2856, 1769, 1507,
1378, 1246, 1189, 1407, 833 cmꢁ1; H NMR (400 MHz,
1
1
CDCl3) d 7.39 (dd, 1H J¼7.8 and 1.6 Hz), 7.21–7.19 (m,
1H), 6.98–6.94 (m, 1H), 6.86–6.84 (m, 1H), 5.44–5.37 (m,
1H), 4.78 (s, 2H), 3.80–3.73 (m, 6H), 1.51 (dd, 3H,
J¼16.8 and 7.2 Hz); 13C NMR (100 MHz, CDCl3) d 15.2,
53.6, 64.5, 65.2, 65.5, 66.1, 114.0, 114.7, 116.1, 122.9,
123.4, 127.8, 129.6, 129.7, 130.8, 153.4, 167.5, 167.5; 31P
NMR (162 MHz, CDCl3) d 23.09; MS (EI) m/z 322
(M+ꢁ1), 323 (M+), 324 (M++1). Anal. Calcd for
C12H16ClO6P: C, 44.67; H, 5.00. Found: C, 44.54; H, 4.94.
Enantiomeric excess determination: HPLC, UV 205 nm,
Chiralcel AS-H, 0.5 mL/min, 20% 2-propanol/80% hexane,
(S) t1¼21.26 min; (R) t2¼23.20 min.
1447, 1249, 1186, 1031, 831 cmꢁ1; H NMR (400 MHz,
CDCl3) d 7.01–6.97 (m, 2H), 6.88–6.84 (m, 2H), 5.40 (p,
1H, J¼7.2 Hz), 4.66 (s, 2H), 3.81–3.76 (m, 6H), 1.51 (dd,
3H, J¼16.8 and 7.2 Hz); 13C NMR (100 MHz, CDCl3)
d 15.2, 53.48, 53.54, 53.6, 64.3, 66.0, 116.0, 116.1, 116.3,
153.9, 156.8, 159.2, 167.9, 168.0; 31P NMR (162 MHz,
CDCl3) d 22.3; MS (EI) m/z 306 (M+), 307 (M++1). Anal.
Calcd for C12H16FO6P: C, 47.07; H, 5.27. Found: C,
46.80; H, 5.14. Enantiomeric excess determination: HPLC,
UV 205 nm, Chiralcel OJ-H, 0.8 mL/min, 20% 2-propa-
nol/80% hexane, (S) t1¼20.76 min; (R) t2¼21.98 min.
4.2.9. (S)-Dimethyl a-(3-trifluoromethylphenoxyacetoxy)
ethyl phosphonate (5i). Yellow liquid; 92% ee; [a]1D4 +10.3
(c 1.10, CHCl3); IR (KBr) 2960, 2857, 1769, 1495, 1457,
4.2.5. (S)-Dimethyl a-(4-chlorophenoxyacetoxy) ethyl
phosphonate (5e). Yellow liquid; 95% ee; [a]1D4 +15.7 (c

H. Liu et al. / Tetrahedron 62 (2006) 11207–11217
11215
1
1332, 1182, 1126, 1068, 834 cmꢁ1; H NMR (400 MHz,
CDCl3) d 8.01 (d, 2H, J¼8.4 Hz), 7.44 (d, 2H, J¼8.4 Hz),
5.54 (p, 1H, J¼7.6 Hz), 3.82 (dd, 6H, J¼10.6 and 2.4 Hz),
1.60 (dd, 3H, J¼16.8 and 7.2 Hz); 13C NMR (100 MHz,
CDCl3) d 15.1, 53.3, 55.5, 63.9, 65.6, 127.7, 128.5, 128.8,
129.8, 131.2, 133,4, 139.9, 164.4; 31P NMR (162 MHz,
CDCl3) d 23.48; MS (EI) m/z 292 (M+ꢁ1), 293 (M+), 294
(M++1), 295 (M++2). Anal. Calcd for C11H14ClO5P: C,
45.14; H, 4.82. Found: C, 45.46; H, 4.93. HPLC, UV
246 nm, Chiralcel OJ-H, 0.5 mL/min, 10% 2-propanol/
90% hexane, (S) t1¼26.32 min; (R) t2¼28.40 min.
CDCl3) d 7.40 (t, 1H, J¼8.0 Hz), 7.28 (d, 1H, J¼8.0 Hz),
7.12–7.08 (m, 2H, J¼7.6 Hz), 5.41 (p, 1H, J¼7.2 Hz),
4.74 (s, 1H), 3.81–3.76 (m, 6H), 1.51 (dd, 3H, J¼16.8 and
7.2 Hz); 13C NMR (100 MHz, CDCl3) d 15.1, 53.4, 53.5,
53.57, 53.63, 64.4, 65.3, 66.1, 111.6, 111.7, 118.3,
118.7, 118.8, 122.6, 125.3, 130.4, 132.0, 132.3, 157.9,
167.47, 167.54; 31P NMR (162 MHz, CDCl3) d 22.9; MS
(EI) m/z 356 (M+), 357 (M++1). Anal. Calcd for
C13H16F3O6P: C, 43.83; H, 4.53. Found: C, 43.92; H, 4.39.
Enantiomeric excess determination: HPLC, UV 205 nm,
Chiralcel AS-H, 0.5 mL/min, 20% 2-propanol/80% hexane,
(S) t1¼13.92 min; (R) t2¼15.20 min.
4.2.14. (S)-Diethyl a-(4-chlorobenzoxy) ethyl phospho-
nate (5n). Yellow liquid; 96% ee; [a]1D4 ꢁ14.49 (c 1.72,
CHCl3); IR (KBr) 2985, 1730, 1594, 1488, 1400, 1265,
1
4.2.10. (S)-Dimethyl a-(4-methylbenzoxy) ethyl phospho-
nate (5j). Colorless liquid; 95% ee; [a]1D4 ꢁ19.61 (c 2.38,
CHCl3); IR (KBr) 2957, 2854, 1725, 1612, 1456, 1266,
1179, 1029, 832, 805, 753, 690 cmꢁ1; 1H NMR (400 MHz,
CDCl3) d 7.92 (d, 2H, J¼8.0 Hz), 7.21 (d, 2H, J¼8.0 Hz),
5.51 (p, 1H, J¼7.2 Hz), 3.82 (dd, 6H, J¼10.4 and 4.4 Hz),
2.37 (s, 3H), 1.55 (dd, 3H, J¼8.8 and 7.2 Hz); 13C NMR
(100 MHz, CDCl3) d 15.2, 21.7, 53.3, 53.6, 63.5, 65.2,
126.6, 129.2, 129.9, 144.2, 165.3; 31P NMR (162 MHz,
CDCl3) d 23.86; MS (EI) m/z 271 (M+-1), 272 (M+), 273
(M++1). Anal. Calcd for C12H17O5P: C, 52.94; H, 6.29.
Found: C, 53.15; H, 6.33. HPLC, UV 246 nm, Chiralcel
OJ-H, 0.5 mL/min, 10% 2-propanol/90% hexane, (S)
t1¼25.46 min; (R) t2¼28.38 min.
1174, 1026, 795, 685 cmꢁ1; H NMR (400 MHz, CDCl3)
d 7.98 (d, 2H, J¼8.4 Hz), 7.40 (d, 2H, J¼8.4 Hz), 5.48 (p,
1H, J¼7.6 Hz), 4.20–4.13 (m, 4H), 1.56 (dd, 3H, J¼16.8
and 7.2 Hz), 1.29 (t, 6H, J¼7.2 Hz); 13C NMR (100 MHz,
CDCl3) d 15.2, 16.5, 62.9, 63.0, 64.4, 66.1, 128.0, 128.9,
131.3, 139.9, 164.6; 31P NMR (162 MHz, CDCl3) d 21.02;
MS (EI) m/z 321 (M+). Anal. Calcd for C13H18ClO5P: C,
48.69; H, 5.66. Found: C, 48.57; H, 5.95. HPLC, UV
246 nm, Chiralcel OJ-H, 0.5 mL/min, 10% 2-propanol/
90% hexane, (S) t1¼14.79 min; (R) t2¼17.13 min.
4.2.15. (S)-Dimethyl a-(4-chlorobenzoxy) propanyl phos-
phonate (5o). Colorless liquid; 91% ee; [a]1D4 +7.14 (c 2.46,
CHCl3); IR (KBr) 2957, 1730, 1594, 1488, 1458, 1401,
1259, 1175, 1030, 833, 758, 684 cmꢁ1
;
1H NMR
4.2.11. (S)-Diethyl a-(4-methylbenzoxy) ethyl phospho-
nate (5k). Pale yellow liquid; 95% ee; [a]1D4 ꢁ22.38
(c 1.82, CHCl3); IR (KBr) 2985, 1724, 1613, 1266, 1023,
(400 MHz, CDCl3) d 7.99 (d, 2H, J¼8.4 Hz), 7.40 (d, 2H,
J¼8.4 Hz), 5.45–5.40 (m, 1H), 3.76 (d, 6H, J¼10.6 Hz),
2.04–1.93 (m, 2H), 1.00 (t, 3H, J¼7.2 Hz); 13C NMR
(100 MHz, CDCl3) d 10.2, 10.4, 23.0, 53.3, 53.4, 68.7,
70.3, 127.7, 128.9, 131.3, 140.0, 164.8; 31P NMR
(162 MHz, CDCl3) d 22.79; MS (EI) m/z 307 (M+), 308
(M++1), 309 (M++2). Anal. Calcd for C12H16ClO5P: C,
47.00; H, 5.26. Found: C, 47.24; H, 4.99. HPLC, UV
246 nm, Chiralcel OJ-H, 0.5 mL/min, 10% 2-propanol/
90% hexane, (S) t1¼21.15 min; (R) t2¼23.25 min.
1
968, 799, 752 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.92
(d, 2H, J¼8.0 Hz), 7.22 (d, 2H, J¼8.0 Hz), 5.49 (p, 1H,
J¼7.2 Hz), 4.19–4.12 (m, 4H), 2.38 (s, 3H), 1.55 (dd, 3H,
J¼16.8 and 7.2 Hz), 1.28 (t, 6H, J¼7.2 Hz); 13C NMR
(100 MHz, CDCl3) d 15.3, 16.5, 21.7, 62.7, 63.0, 63.9,
65.6, 126.8, 129.2, 129.9, 144.2, 165.5; 31P NMR
(162 MHz, CDCl3) d 21.38; MS (EI) m/z 300 (M+).
Anal. Calcd for C14H21ClO5P: C, 56.00; H, 7.05. Found:
C, 56.24; H, 7.15. HPLC, UV 246 nm, Chiralcel
OJ-H, 0.5 mL/min, 10% 2-propanol/90% hexane, (S) t1¼
14.30 min; (R) t2¼16.40 min.
4.2.16. (S)-Diethyl a-(4-chlorobenzoxy) propanyl phos-
phonate (5p). Colorless liquid; 92% ee; [a]1D4 +6.55
(c 2.28, CHCl3); IR (KBr) 2981, 1730, 1594, 1488, 1400,
1256, 1094, 1024, 971, 757 cmꢁ1 1H NMR (400 MHz,
;
4.2.12. (S)-Dimethyl a-(4-methylbenzoxy) propanyl
phosphonate (5l). Colorless liquid; 94% ee; [a]1D4 +8.63
(c 1.16, CHCl3); IR (KBr) 2957, 2854, 1725, 1613, 1457,
CDCl3) d 8.02 (d, 2H, J¼8.4 Hz), 7.45 (d, 2H, J¼8.4 Hz),
5.42 (m, 1H), 4.18–4.13 (m, 4H), 2.00 (m, 2H), 1.31 (q,
6H, J¼7.2 Hz), 1.03 (t, 3H, J¼7.2 Hz); 13C NMR
(100 MHz, CDCl3) d 10.4, 10.5, 16.6, 23.0, 62.9, 69.1,
70.8, 127.9, 129.0, 131.3, 134.0, 165.0; 31P NMR
(162 MHz, CDCl3) d 20.26; MS (EI) m/z 333 (M+ꢁ2), 335
(M+), 337 (M++2). Anal. Calcd for C14H20ClO5P: C,
50.23; H, 6.02. Found: C, 50.49; H, 5.86. HPLC, UV
246 nm, Chiralcel OJ-H, 0.5 mL/min, 10% 2-propanol/
90% hexane, (S) t1¼12.42 min; (R) t2¼13.35 min.
1256, 1178, 1026, 835, 753 cmꢁ1 1H NMR (400 MHz,
;
CDCl3) d 7.98 (d, 2H, J¼8.0 Hz), 7.26 (d, 2H, J¼8.0 Hz),
5.48 (m, 1H), 3.79 (d, 6H, J¼10.8 Hz), 2.42 (s, 3H), 2.06–
1.99 (m, 2H), 1.03 (t, 3H, J¼7.2 Hz); 13C NMR
(100 MHz, CDCl3) d 10.3, 21.8, 23.1, 53.3, 53.6, 68.3,
67.0, 126.6, 129.4, 130.1, 144.4, 165.5; 31P NMR
(162 MHz, CDCl3) d 23.15; MS (EI) m/z 286 (M+). Anal.
Calcd for C13H19O5P: C, 54.54; H, 6.69. Found: C, 54.32;
H, 6.81. HPLC, UV 246 nm, Chiralcel OJ-H, 0.5 mL/min,
10% 2-propanol/90% hexane, (S) t1¼21.95 min; (R)
t2¼23.66 min.
4.2.17. (S)-Dimethyl a-(2-furancarbonyl oxo) ethyl phos-
phonate (5q). Pale yellow liquid; 96% ee; [a]1D4 ꢁ18.6 (c
0.68, CHCl3); IR (KBr) 2959, 2856, 1733, 1579, 1474,
1395, 1323, 1294, 1246, 1179, 1117, 1049, 939, 825 cmꢁ1
;
4.2.13. (S)-Dimethyl a-(4-chlorobenzoxy) ethyl phospho-
nate (5m). Pale yellow liquid; 95% ee; [a]1D4 ꢁ19.6 (c 1.20,
CHCl3); IR (KBr) 2956, 1734, 1594, 1455, 1401, 1265,
1177, 1025, 832, 802, 759, 685 cmꢁ1; 1H NMR (400 MHz,
1H NMR (400 MHz, CDCl3) d 7.62 (d, 1H, J¼1.6 Hz),
7.26 (d, 1H, J¼3.6 Hz), 6.54 (dd, 1H, J¼3.6 and 1.6 Hz),
5.56–5.48 (m, 1H), 3.87–3.79 (m, 6H), 1.60 (dd, 3H,
J¼16.8 and 7.2 Hz); 13C NMR (100 MHz, CDCl3) d 15.3,

11216
H. Liu et al. / Tetrahedron 62 (2006) 11207–11217
53.5, 53.6, 53.7, 53.8, 63.9, 65.6, 112.2, 119.1, 143.9, 147.1,
157.4, 157.5; 31P NMR (162 MHz, CDCl3) d 23.71; MS (EI)
m/z 248 (M+ꢁ1), 249 (M++1). Anal. Calcd for C9H13O6P: C,
43.56; H, 5.28. Found: C, 43.81; H, 5.19. Enantiomeric
excess determination: HPLC, UV 254 nm, Chiralcel OJ-H,
0.8 mL/min, 10% 2-propanol/90% hexane, (S) t1¼
20.35 min; (R) t2¼25.83 min.
d 23.71; MS (EI) m/z 226 (M+), 227 (M++1), 228 (M++2).
Anal. Calcd for C7H15O6P: C, 37.17; H, 6.69. Found: C,
36.88; H, 6.49. Enantiomeric excess determination: HPLC,
UV 205 nm, Chiralcel AS-H, 0.5 mL/min, 20% 2-propanol/
80% hexane, (S) t1¼15.44 min; (R) t2¼16.38 min.
4.2.22. (S)-Dimethyl a-(phenylacetoxy) ethyl phospho-
nate (5v). Colorless liquid; 91% ee; [a]1D4 +7.71 (c 0.74,
CHCl3); IR (KBr) 2957, 2854, 1745, 1455, 1247, 1148,
4.2.18. (S)-Dimethyl a-(2-thiophenecarbonyl oxo) ethyl
phosphonate (5r). Colorless liquid; 95% ee; [a]1D4 ꢁ29.6
(c 3.64, CHCl3); IR (KBr) 2957, 1720, 1524, 1456, 1417,
1
1049, 832 cmꢁ1; H NMR (400 MHz, CDCl3) d 7.33–7.27
(m, 5H), 5.30 (p, 1H, J¼7.6 Hz), 3.72–3.68 (m, 8H), 1.47
(dd, 3H, J¼16.4 and 7.2 Hz); 13C NMR (100 MHz,
CDCl3) d 15.2, 41.4, 53.4, 53.5, 63.9, 65.6, 127.5, 128.8,
129.5, 133.6, 170.5; 31P NMR (162 MHz, CDCl3) d 24.1;
MS (EI) m/z 272 (M+). Anal. Calcd for C12H17O5P: C,
52.94; H, 6.29. Found: C, 52.89; H, 6.14. Enantiomeric
excess determination: HPLC, UV 205 nm, Chiralcel
AD-H, 0.5 mL/min, 20% 2-propanol/80% hexane, (S) t1¼
10.09 min; (R) t2¼10.88 min.
1260, 1180, 1029, 830, 795, 749 cmꢁ1
;
1H NMR
(400 MHz, CDCl3) d 7.85 (d, 1H, J¼3.6 Hz), 7.60 (d, 1H,
J¼4.8 Hz), 7.12 (t, 1H, J¼4.4 Hz), 5.50 (p, 1H, J¼7.6 Hz),
3.86–3.80 (M, 6H), 1.58 (dd, 3H, J¼16.4 and 7.2 Hz); 13C
NMR (100 MHz, CDCl3) d 15.3, 53.4, 53.7, 64.2, 65.9,
128.0, 132.8, 133.3, 143.3, 140.0, 161.1; 31P NMR
(162 MHz, CDCl3) d 23.21; MS (EI) m/z 263 (M+ꢁ1), 264
(M+), 265 (M++1). Anal. Calcd for C9H13O5PS: C, 40.91;
H, 4.96. Found: C, 41.13; H, 4.61. HPLC, UV 246 nm,
Chiralcel OJ-H, 0.5 mL/min, 10% 2-propanol/90% hexane,
(S) t1¼53.43 min; (R) t2¼63.24 min.
4.2.23. (S)-Dimethyl (1-hydroxyethyl) phosphonate 6a. A
purified sample of 5a (530 mg, 1.5 mmol) was combined
with anhydrous K2CO3 (620 mg, 3 equiv) in MeOH. The re-
action mixture was stirred for 2 h at room temperature.
MeOH was removed by evaporation and the residue was
passed through a silica gel column using ethyl acetate as
an eluant to give pure product 6a (50 mg, 22% yield) as
colorless oil. Spectral data matched with those reported in
the literature.18
4.2.19. (S)-Diethyl a-(2-thiophenecarbonyl oxo) ethyl
phosphonate (5s). Yellow liquid; 95% ee; [a]1D4 ꢁ28.7 (c
1.12, CHCl3); IR (KBr) 2985, 1717, 1524, 1417, 1362,
1
1257, 1094, 1046, 1024, 970 cmꢁ1; H NMR (400 MHz,
CDCl3) d 7.86–7.85 (m, 1H), 7.61 (dd, 1H, J¼6.8 and
1.2 Hz), 7.14-7.11 (m, 1H), 5.48 (p, 1H, J¼7.6 Hz), 4.25–
4.17 (m, 4H), 1.59 (dd, 3H, J¼16.4 and 7.2 Hz), 1.34 (t,
6H, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3) d 15.4,
16.57, 16.63, 16.7, 62.9, 63.0, 63.2, 64.6, 66.3, 128.1,
133.0, 134.2, 161.0, 161.1; 31P NMR (162 MHz, CDCl3)
d 21.25; MS (EI) m/z 291 (M+ꢁ1), 292 (M+). Anal. Calcd
for C11H17O5PS: C, 45.20; H, 5.86. Found: C, 45.60;
H, 5.59. Enantiomeric excess determination: HPLC, UV
254 nm, Chiralcel OJ-H, 0.8 mL/min, 10% 2-propanol/
90% hexane, (S) t1¼8.98 min; (R) t2¼10.70 min.
Acknowledgements
We are grateful to the National Basic Research Program of
China (2004CCA00100, 2003CB114400), the Natural Sci-
ence Foundation of China (20472021), the program for new
century excellent talents in university (NCET-05-0672), and
the Cultivation Fund of the Key Scientific and Technical
Innovation Project (Ministry of Education of China, No
705039) for support of this research. We thank Drs. Richard
Pederson and Joel Austin for fruitful discussions.
4.2.20. (S)-Dimethyl a-(2-thiophenecarbonyl oxo) prop-
anyl phosphonate (5t). Yellow liquid; 94% ee; [a]D14
+2.79 (c 1.60, CHCl3); IR (KBr) 2957, 2854, 1718, 1523,
1
1416, 1362, 1254, 1096, 1051 cmꢁ1; H NMR (400 MHz,
Supplementary data
CDCl3) d 7.88 (dd, 1H, J¼3.6 and 1.2 Hz), 7.62 (dd, 1H,
J¼4.8 and 1.2 Hz), 7.14 (dd, 1H, J¼4.8 and 3.6 Hz), 5.45–
5.39 (m, 1H), 3.84–3.79 (m, 6H), 2.06–1.95 (m, 2H), 1.05
(t, 3H, J¼7.4 Hz); 13C NMR (100 MHz, CDCl3) d 10.3,
10.4, 23.1, 53.36, 53.42, 53.65, 53.72, 68.8, 70.5, 128.1,
132.7, 133.4, 134.4, 161.4; 31P NMR (162 MHz, CDCl3)
d 23.18; MS (EI) m/z 278 (M+), 279 (M++1). Anal. Calcd
for C10H15O5PS: C, 43.16; H, 5.43. Found: C, 43.00;
H, 5.21. Enantiomeric excess determination: HPLC, UV
246 nm, Chiralcel OJ-H, 1 mL/min, 10% 2-propanol/90%
hexane, (S) t1¼17.23 min; (R) t2¼21.65 min.
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.09.011.
References and notes
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