Asymmetric synthesis of 2-alkyl-3-phosphonopropanoic acid derivatives via Rh-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1016/j.tetasy.2011.12.002

The commercially available ferrocene-based diphosphine ligand (S _c,S_Fc)-TaniaPhos was found to be highly effective in the Rh-catalyzed asymmetric hydrogenation of 3-aryl-2-(phosphonomethyl)propenates. Excellent enantioselectivity (90

Full text of DOI:10.1016/j.tetasy.2011.12.002

Tetrahedron: Asymmetry 22 (2011) 2117–2123
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Tetrahedron: Asymmetry
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Asymmetric synthesis of 2-alkyl-3-phosphonopropanoic acid derivatives via
Rh-catalyzed asymmetric hydrogenation
Li-Bin Luo a, Dao-Yong Wang b, Xiao-Mao Zhou a, , Zhuo Zheng a,b, Xiang-Ping Hu b,
⇑
⇑
a Institute of Pesticide, Hunan Agricultural University, Changsha 410128, China
b Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 November 2011
Accepted 6 December 2011
The commercially available ferrocene-based diphosphine ligand (Sc,SFc)-TaniaPhos was found to be highly
effective in the Rh-catalyzed asymmetric hydrogenation of 3-aryl-2-(phosphonomethyl)propenates.
Excellent enantioselectivity (90–98% ee) and high catalytic activity (S/C up to 1000) have been achieved,
which represents the best results reported so far.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
propenoic acids with a (R)-Cl-MeO-BIPHEP/Ru catalyst, for most
substrates the enantioselectivities were less satisfactory. In 2009,
Chiral 2-alkyl-3-phosphonopropanoic acid derivatives have re-
ceived considerable attention over the past few years in bioorganic
and medicinal chemistry because of their important biological
activities as phosphonate and phosphinate enzyme inhibitors.1
The present synthesis of enantioenriched 2-alkyl-3-phosphono-
propanoic acid derivatives mainly focuses on asymmetric induc-
tion using a chiral auxiliary.2 However, these methods are not
catalytic, requiring stoichiometric chiral materials, and in many
cases the diastereoselectivity obtained is unsatisfactory. The need
for the development of an efficient and catalytic method for the
enantioselective synthesis of chiral 2-alkyl-3-phosphonopropanoic
acid derivatives is therefore apparent. Over past few decades, opti-
cally active succinates have been prepared efficiently via the cata-
lytic asymmetric hydrogenation of itaconate derivatives with a
variety of chiral P-ligand/Rh complexes.3 Due to their structural
similarity, we therefore envisioned that the catalytic asymmetric
hydrogenation of 2-(phosphonomethyl)propenoates (phosphono
analogues of itaconates) should be an ideal approach for the prep-
aration of optically active 2-alkyl-3-phosphonopropanoic acid
derivatives. In 2007 Spilling and co-workers reported the first
example of the enantioselective synthesis of chiral 2-alkyl-3-
phosphonopropanoic acids or esters via catalytic asymmetric
hydrogenation of the corresponding 2-(phosphonomethyl)pro-
penoate derivatives.4 However, the level of asymmetric induction
with Rh/diphosphine (e.g., DIPAMP, DuPHOS, ferrotane, Tangphos)
complexes were found to be very low (0–52% ee). Although up to
91% ee was observed in the hydrogenation of 2-(phosphonomethyl)
we reported a new ferrocene-based 1,5-diphosphine ligand,
(Rc,SFc)-ImiFerroPhos 1, which displayed high enantioselectivities
in the Rh-catalyzed asymmetric hydrogenation of various 3-aryl-
2-(phosphonomethyl)propenoates.5 However, the synthesis of this
ligand is very difficult. The search of a new catalytic system, one
that would be commercially available, for the enantioselective
hydrogenation of a wider range of 2-(phosphonomethyl)propeno-
ate derivatives is still desirable. Due to the structural similarity,
we surmised that the commercially available ferrocenyl 1,5-
diphosphine ligand, (Sc,SFc)-TaniaPhos 2 (Fig. 1), might be an ideal
alternative. As a result, we herein report our detailed studies on
the Rh-catalyzed asymmetric hydrogenation of 3-substituted 2-
(phosphonomethyl)propenoates with (Sc,SFc)-TaniaPhos 2.
Ph2P
Ph2P
N
N
Ph2P
Ph2P
Fe
Fe
N
(Sc,SFc)-TaniaPhos 2
(Rc,SFc)-ImiFerroPhos 1
Figure 1. The structure of (Rc,SFc)-ImiFerroPhos 1 and (Sc,SFc)-TaniaPhos 2.
2. Results and discussion
2.1. Synthesis of 3-substituted 2-(phosphonomethyl)
propenoates
⇑
Corresponding authors. Tel.: +86 411 84379276; fax: +86 411 84684746 (X.-
P.H).
3-Substituted 2-(phosphonomethyl)propenoates 7 are prepared
E-mail addresses: zhouxm1972@126.com (X.-M. Zhou), xiangping@dicp.ac.cn
from various aldehydes via a two-step transformation as outlined
(X.-P. Hu).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.12.002

2118
L.-B. Luo et al. / Tetrahedron: Asymmetry 22 (2011) 2117–2123
DABCO, PEG-400
rt, 2-7d
OR1
R
OH
O
(R2O)2PCl
R
+
O
OR1
O
Et3N, Et2O
-10 oC, 20 min
3
4
5
COOR1
R
O
O
P(OR2)2
OR1
R
70-100oC, 2-3 h
OR2
OR2
P
O
6
7
Scheme 1. Synthesis of 3-substituted 2-(phosphonomethyl)propenoates 7.
in Scheme 1. Initially, the Baylis–Hillman reaction of aldehydes
with acrylates gave intermediate allylic alcohols 5. The treatment
of Baylis–Hillman adducts 5 with dialkyl phosphorchloridite in
the presence of triethylamine followed by heating the crude inter-
mediates 6 for 2–3 h at 70–100 °C formed the desired 2-(phospho-
nomethyl)propenoates 7, which can be isolated from the reaction
mixture by column chromatography in moderate to good yields.
The Arbuzov rearrangement of the dialkyl allyl phosphites 6 to
the corresponding 2-(phosphonomethyl)propenoates 7 is a highly
stereoselective process, giving exclusively the corresponding 2-
(phosphonomethyl)propenoates 7 with the Z-configuration.6
was performed in CH2Cl2 at room temperature under 20 bar of
H2 pressure for 24 h and with an Rh/ligand ratio of 1:1.1; the re-
sults are listed in Table 1. This ligand showed excellent enantiose-
lectivity (up to 96% ee) (entry 1), and was higher than that
obtained with (Rc,SFc)-ImiFerroPhos 1 (93% ee) under the same
hydrogenation conditions (entry 2). This result suggested the po-
tential of this commercially available diphosphine, (Sc,SFc)-Tania-
Phos 2, in this hydrogenation. We next investigated the effect of
the ester functional group of 2-(phosphonomethyl)propenoates
on this hydrogenation. Replacing an ethyl ester 7a with a methyl
ester 7b had less effect on the reactivity and enantioselectivity,
and methyl 2-[(dimethoxyphosphoryl)methyl]-3-phenyl-2-pro-
penoate 7b was hydrogenated in >95% conversion and with 95%
ee (entry 3). However, the hydrogenation of substrate 7c with a
bulky t-Bu ester group resulted in a significant decrease in reactiv-
ity and enantioselectivity (entry 4). The introduction of the bulkier
ester functional group onto the phosphoryl moiety also lowered
both the conversion and enantioselectivity (entries 5 and 6). These
2.2. The Rh-catalyzed asymmetric hydrogenation of 3-
substituted 2-(phosphonomethyl)propenoates with (Sc,SFc)-
TaniaPhos
Initially, the hydrogenation of ethyl 2-[(dimethoxyphospho-
ryl)methyl]-3-phenyl-2-propenoate 7a with (Sc,SFc)-TaniaPhos 2
Table 1
Rh-catalyzed asymmetric hydrogenation of 3-phenyl-2-(phosphonomethyl)propenoatesa
[Rh(COD)2]SbF6 (1 mol %)
(Sc,SFc)-TaniaPhos (1.1 mol %)
CO2R1
CO2R1
*
OR2
OR2
OR2
OR2
H2 (20 bar), CH2Cl2, rt, 24 h
P
P
O
O
7a-e
8a-e
Entry
Ligand
Substrate (R1, R2)
Solvent
H2 (bar)
Conversionb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
TaniaPhos 2
ImiFerroPhos 1
TaniaPhos 2
TaniaPhos 2
TaniaPhos 2
TaniaPhos 2
TaniaPhos 2
TaniaPhos 2
TaniaPhos 2
TaniaPhos 2
TaniaPhos 2
TaniaPhos 2
ImiFerroPhos 1
ImiFerroPhos 1
7a (Et, Me)
7a (Et, Me)
7b (Me, Me)
7c (t-Bu, Me)
7d (Et, i-Pr)
7e (Et, Ph)
7a (Et, Me)
7a (Et, Me)
7a (Et, Me)
7a (Et, Me)
7a (Et, Me)
7a (Et, Me)
7a (Et, Me)
7a (Et, Me)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeOH
THF
Toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
20
20
20
20
20
20
20
20
20
50
10
50
10
50
>95
>95
>95
77
77
68
>95
>95
87
>95
>95
>95
>95
<10
96
93
95
82
79
83
70
88
83
95
96
88d
94
d,e
—
a
Reagents and conditions: 1 mL of solvent, 0.25 mmol of substrate 7a–e, 1 mol % of catalyst prepared in situ from [Rh(COD)2]SbF6 and 1.1 equiv of TaniaPhos, 20 bar of H2
pressure, room temperature for 24 h, unless otherwise noted.
b
Conversions were determined by 1H NMR.
Enantiomeric excesses were determined by HPLC, using a chiral AD-H, or OD-H column.
Catalyst loading, 0.1 mol %.
Not determined.
c
d
e

L.-B. Luo et al. / Tetrahedron: Asymmetry 22 (2011) 2117–2123
2119
results suggested that the ester functional group of 2-(phospho-
nomethyl)propenoates had a significant influence on the reactivity
and enantioselectivity, and the substrate with the less sterically
hindered ester functional group is favorable for this hydrogenation.
The hydrogenation is also sensitive to the solvent used. Protic sol-
vents, such as MeOH, tended to give lower enantioselectivity (en-
try 7). The reaction proceeded smoothly in THF, giving slightly
lower enantioselectivity (entry 8). Toluene proved to be an inferior
solvent, in which low conversion was observed (entry 9). The
pressure of H2 had less influence on the reactivity and enantiose-
lectivity at a catalyst loading of 1 mol % (entries 10 and 11).
Lowering the catalyst loading to 0.1 mol %, however, required a
higher H2 pressure of 50 bar in order to complete the hydrogena-
tion with reduced enantioselectivity (88% ee) (entry 12). In a
contrast, (Rc,SFc)-ImiFerroPhos only showed low conversion under
the same catalyst loadings (0.1 mol %) and hydrogenation condi-
tions (entry 14). This result demonstrated the high efficiency of
(Sc,SFc)-TaniaPhos in the Rh-catalyzed asymmetric hydrogenation
of 2-(phosphonomethyl)propenoates.
Having established the optimal ester functional group of
the 2-(phosphonomethyl)propenoates and the hydrogenation
conditions, we next examined the Rh-catalyzed asymmetric hydro-
genation of a variety of 3-substituted 2-[(dimethoxyphospho-
ryl)methyl]-2-propenoates 7f–q with (Sc,SFc)-TaniaPhos, and the
results are summarized in Table 2. Initially, the hydrogenation of
3-aryl substituted substrates 7f–o was investigated. The electronic
nature of the para-substituents on the phenyl ring of these sub-
strates had no significant effect on the enantioselectivity. All sub-
strates with a para-substituent gave high enantioselectivities
(entries 2–5). The positions of the substituent on the phenyl ring
had some effect on the enantioselectivities. All of the substrates
with a methoxy group on the different position of the phenyl ring
were hydrogenated with high enantioselectivity (entries 5–7); the
substrate with a 2-methoxy group gave the best enantioselectivity
(97% ee, entry 7). However, the substrates with a Cl-substitutent
showed entirely different reactivities towards this hydrogenation
(entries 3, 8 and 9). The substrates bearing a 3-Cl and 4-Cl group
were hydrogenated in high yields and enantioselectivities (entries
3 and 8), while the 2-Cl substituted substrate only gave low con-
version (entry 9). The hydrogenation of the substrates with a het-
eroaromatic substituent also led to good enantioselectivities
(entries 10 and 11). The hydrogenation of 2-thienyl substituted
substrate 7o provided the best enantioselectivity of up to 98% ee
(entry 11). In comparison with those obtained with (Rc,SFc)-ImiFer-
roPhos 1 (as shown in parentheses in Table 2), the present catalytic
system normally induced higher enantioselectivity. In particular,
the present catalytic system displayed excellent enantioselectivity
(92% ee) and high yields (99%) in the hydrogenation of ethyl 3-(3-
chlorophenyl)-2-[(dimethoxyphosphoryl)methyl]-2-propenoate 7l
(entry 8), while the corresponding Rh/(Rc,SFc)-ImiFerroPhos
complex gave only very low conversion (entry 8). These results
demonstrated the high efficiency of the present catalytic system
in the Rh-catalyzed asymmetric hydrogenation of 3-aryl-2-(phos-
phonomethyl)propenoates. The shortcoming of the present cata-
lytic system lies in its inferior performance in the hydrogenation
of 3-alkyl substituted substrates. Thus, the hydrogenation of ethyl
2-[(dimethoxyphosphoryl)methyl]-2-propenoate 7p gave full
conversion but with very low enantioselectivity (entry 12); while
the hydrogenation of ethyl 2-[(dimethoxyphosphoryl)methyl]-4-
methyl-2-pentenoate 7q only showed very low conversion
(entry 13).
3. Conclusion
In conclusion, we have found that a commerically available
ferrocene-based diphosphine ligand (Sc,SFc)-TaniaPhos is highly
effective in the Rh-catalyzed asymmetric hydrogenation of
2-(phosphonomethyl)propenoates. In comparison with reactivities
obtained with (Rc,SFc)-ImiFerroPhos, the present catalytic system
shows higher reactivities (S/C up to 1000/1) and generally better
Table 2
Rh-catalyzed asymmetric hydrogenation of 3-substituted 2-(phosphonomethyl)propenoatesa
[Rh(COD)2]SbF6 (1 mol %)
(Sc,SFc)-TaniaPhos (1.1 mol %)
CO2Et
CO2Et
*
R
R
OMe
OMe
P
P
H2 (10 bar), CH2Cl2, rt, 24 h
OMe
OMe
O
O
8a, 8f-q
7a, 7f-q
Entry
Substrate
R
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
7a
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7q
Ph
99
99
97
98
97
98
95
99
35
97
98
98
<10
96 (94)
91 (91)
96 (92)
95 (89)
95 (95)
95 (92)
97 (93)
92 (—)
4-FC6H4
4-ClC6H4
4-NO2C6H4
4-MeOC6H4
3-MeOC6H4
2-MeOC6H4
3-ClC6H4
2-ClC6H4
2-Furyl
d
—
90 (90)
98 (98)
2-Thienyl
H
i-Pr
<10
—
d
a
Reagents and conditions: 2 mL of CH2Cl2, 0.5 mmol of substrate, 1 mol % of catalyst prepared in situ from [Rh(COD)2]SbF6 and
1.1 equiv of TaniaPhos, 10 bar of H2 pressure, room temperature for 24 h.
b
Isolated yields.
c
Enantiomeric excesses were determined by HPLC using a chiral AD-H, OD-H or OJ-H column. Enantiomeric excesses of 8p–q were
determined by GC using a
c
-DEX-225 capillary. Those in parentheses were obtained with (Rc,SFc)-ImiFerroPhos.
d
Not determined due to low conversions.

2120
L.-B. Luo et al. / Tetrahedron: Asymmetry 22 (2011) 2117–2123
enantioselectivities. With (Sc,SFc)-TaniaPhos, various 3-aryl-2-
(phosphonomethyl)-propenoates were hydrogenated in 90–98%
ee, which represents the best results reported to date.
4.2.3. t-Butyl 2-[(dimethoxyphosphoryl)methyl]-3-phenyl-2-
propenoate 7c4
Yield: 71%. Oil. 1H NMR (400 MHz, CDCl3): d 1.56 (s, 9H), 3.20 (d,
J = 22.6 Hz, 2H), 3.70 (d, J = 10.8 Hz, 6H), 7.34 (t, J = 7.4 Hz, 1H),
7.41 (t, J = 7.3 Hz, 2H), 7.55 (d, J = 7.5 Hz, 2H), 7.72 (d, J = 5.5 Hz,
1H); 13C NMR (100 MHz, CDCl3): d 25.3 (d, J = 139 Hz), 28.0, 52.7
(d, J = 7 Hz), 81.3, 125.2 (d, J = 12 Hz), 128.6, 128.7, 129.2, 135.1,
140.6 (d, J = 11 Hz), 166.5; 31P NMR (162 MHz, CDCl3): d 29.3.
4. Experimental
4.1. General
All reactions were conducted under either a nitrogen or argon
atmosphere unless otherwise noted. Anhydrous procedures were
conducted using oven dried or flame dried glassware and standard
syringe and cannula transfer techniques. Hydrogenation was per-
formed in a stainless steel autoclave. Solvents were of reagent
grade, dried and distilled before use following standard proce-
dures. 1H NMR spectra were recorded on a 400 MHz spectrometer.
Chemical shifts were reported in ppm from tetramethylsilane with
the solvent resonance as the internal standard (CDCl3, d = 7.26).
Data are reported as follows: chemical shift (ppm), multiplicity
(s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), cou-
pling constants (Hz), integration, and assignment. 13C NMR data
were collected on a 100 MHz spectrometer with complete proton
decoupling. Chemical shifts are reported in ppm from the tetra-
methylsilane with the solvent resonance as an internal standard
(CDCl3, d = 77.0). 31P NMR spectra were recorded on a 162 MHz
spectrometer. The enantiomeric excesses were determined by chi-
4.2.4. Ethyl 2-[(diisopropoxyphosphoryl)methyl]-3-phenyl-2-
propenoate 7d
Yield: 32%. Oil. 1H NMR (400 MHz, CDCl3): d 1.26 (d, J = 6.2 Hz,
6H), 1.30 (d, J = 6.2 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H), 3.21 (d,
J = 22.6 Hz, 2H), 4.30 (q, J = 7.1 Hz, 2H), 4.71 (m, 2H), 7.34 (t,
J = 7.2 Hz, 1H), 7.40 (t, J = 7.4 Hz, 2H), 7.64 (d, J = 7.6 Hz, 2H), 7.77
(d, J = 5.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 14.2, 23.8 (d,
J = 5 Hz), 24.0 (d, J = 2 Hz), 27.5 (d, J = 141 Hz), 61.1, 70.6 (d,
J = 6 Hz), 124.6 (d, J = 11 Hz), 128.4, 128.8, 129.5, 135.0, 140.7 (d,
J = 11 Hz), 167.6; 31P NMR (162 MHz, CDCl3): d 24.4. HRMS (ESI):
calcd for C18H27O5P [M+Na]+: 377.1494, found: 377.1498.
4.2.5. Ethyl 2-[(diphenoxyphosphoryl)methyl]-3-phenyl-2-
propenoate 7e
Yield: 57%. Viscous oil. 1H NMR (400 MHz, CDCl3): d 1.29 (t,
J = 7.1 Hz, 3H), 3.59 (d, J = 22.6 Hz, 2H), 4.26 (q, J = 7.1 Hz, 2H),
7.10–7.15 (m, 6H), 7.28 (m, 4H), 7.35–7.40 (m, 3H), 7.59 (d,
J = 7.3 Hz, 2H), 7.94 (d, J = 5.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 14.2, 26.9 (d, J = 142 Hz), 61.5, 120.5 (d, J = 4 Hz), 123.2 (d,
J = 12 Hz), 125.2 (d, J = 14 Hz), 128.8, 129.1, 129.4, 129.7, 134.7,
142.5 (d, J = 12 Hz), 150.5 (d, J = 9 Hz), 167.2; 31P NMR (162 MHz,
ral HPLC. Optical rotations were reported as follows: ½a D25
ꢀ
(c g/
100 mL, in solvent).
4.2. General procedure for preparation of 3-substituted 2-
(phosphonomethyl)-propenoates
CDCl3):
d
19.3. HRMS (ESI): calcd for C24H23O5P [M+Na]+:
445.1181, found: 445.1193.
To a stirred solution of aldehyde (50 mmol) and acrylate
(75 mmol) in 30 mL of PEG (400), was added DABCO (50 mmol).
The solution was stirred for 2–7 days, then it was diluted with
Et2O, washed with 1 N HCl and water, dried over Na2SO4, filtered
and evaporated in vacuo to give the crude adduct. The crude mix-
ture was purified by column chromatography (SiO2, hexane/ethyl
acetate, 5:1) to give the pure product.
To a stirred solution of the Baylis–Hillman adduct (20 mmol)
and Et3N (2.02 g, 20 mmol) in Et2O (50 mL), dimethyl phosphoro-
chloridite (2.57 g, 20 mmol) was added dropwise at ꢁ10 °C under
argon, and stirring was continued for 20 min at ꢁ10 °C. The precip-
itate was filtered off and washed with Et2O (2 ꢂ 10 mL). The filtrate
was evaporated and the residue was heated at 70–100 °C under ar-
gon for 2–3 h. The resultant product was purified by column chro-
matography (SiO2, hexane/ethyl acetate, 2:1).
4.2.6. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(4-
fluorophenyl)-2-propenoate 7f
Yield: 59%. Oil. 1H NMR (400 MHz, CDCl3): d 1.37 (t, J = 7.1 Hz,
3H), 3.20 (dd, J = 22.6, 4.6 Hz, 2H), 3.74 (dd, J = 10.9, 4.8 Hz, 6H),
4.31 (q, J = 7.2 Hz, 2H), 7.10 (m, 2H), 7.60 (m, 2H), 7.77 (d,
J = 5.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 14.2, 25.2 (d,
J = 140 Hz), 52.7 (d, J = 6 Hz), 61.3, 115.6 (d, J = 22 Hz), 123.4 (d,
J = 12 Hz), 130.8, 131.3 (d, J = 8 Hz), 140.4 (d, J = 11 Hz), 161.6,
164.1, 167.1; 31P NMR (162 MHz, CDCl3): d 28.7. HRMS (ESI): calcd
for C14H18FO5P [M+Na]+: 339.0774, found: 339.0782.
4.2.7. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(4-
chlorophenyl)-2-propenoate 7g
Yield: 59%. Oil. 1H NMR (400 MHz, CDCl3): d 1.37 (t, J = 7.1 Hz,
3H), 3.20 (d, J = 22.6 Hz, 2H), 3.74 (dd, J = 10.9, 4.8 Hz, 6H), 4.31
(q, J = 7.1 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H),
7.76 (d, J = 5.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 14.2, 25.2
(d, J = 139 Hz), 52.7 (d, J = 6 Hz), 61.3, 124.2 (d, J = 12 Hz), 128.8,
130.6, 133.1 (d, J = 3 Hz), 134.8, 140.1 (d, J = 11 Hz), 167.0; 31P
NMR (162 MHz, CDCl3): d 28.5. HRMS (ESI): calcd for C14H18ClO5P
[M+Na]+: 355.0478, found: 355.0480.
4.2.1. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-phenyl-2-
propenoate 7a7
Yield: 54%. Oil. 1H NMR (400 MHz, CDCl3): d 1.37 (t, J = 7.1 Hz,
3H), 3.24 (d, J = 22.6 Hz, 2H), 3.70 (dd, J = 10.9, 2.8 Hz, 6H), 4.32
(q, J = 7.2 Hz, 2H), 7.35 (m, 1H), 7.42 (m, 2H), 7.56 (d, J = 7.5 Hz,
1H), 7.82 (d, J = 5.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 14.3,
25.2 (d, J = 140 Hz), 52.7 (d, J = 6 Hz), 61.3, 123.8 (d, J = 11 Hz),
128.6, 129.0, 129.3, 134.8, 141.6 (d, J = 11 Hz), 167.4; 31P NMR
(162 MHz, CDCl3): d 28.9.
4.2.8. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(4-
nitrophenyl)-2-propenoate 7h
Yield: 51%. White crystals, mp: 78–80 °C. 1H NMR (400 MHz,
CDCl3): d 1.38 (t, J = 7.2 Hz, 3H), 3.17 (d, J = 23.2 Hz, 2H), 3.75 (d,
J = 10.8 Hz, 6H), 4.34 (q, J = 7.2 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H),
7.82 (d, J = 5.6 Hz, 1H), 8.28 (d, J = 8.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d 14.2, 25.5 (d, J = 139 Hz), 52.9 (d, J = 6 Hz),
61.8, 123.8, 127.1 (d, J = 12 Hz), 138.9 (d, J = 11 Hz), 141.3, 147.6,
166.6; 31P NMR (162 MHz, CDCl3): d 27.9. HRMS (ESI): calcd for
4.2.2. Methyl 2-[(dimethoxyphosphoryl)methyl]-3-phenyl-2-
propenoate 7b4,8
Yield: 49%. Oil. 1H NMR (400 MHz, CDCl3): d 3.23 (d, J = 22.5 Hz,
2H), 3.70 (d, J = 10.8 Hz, 6H), 3.85 (s, 3H), 7.35 (d, J = 7.2 Hz, 1H),
7.41 (t, J = 7.2 Hz, 2H), 7.56 (d, J = 7.2 Hz, 2H), 7.82 (d, J = 5.1 Hz,
1H); 13C NMR (100 MHz, CDCl3): d 25.2 (d, J = 140 Hz), 52.3, 52.6
(d, J = 6 Hz), 123.4 (d, J = 12 Hz), 128.6, 129.0, 129.2, 134.6, 141.7
(d, J = 10 Hz), 167.7; 31P NMR (162 MHz, CDCl3): d 28.8.
C
14H18NO7P [M+Na]+: 366.0719, found: 366.0728.

L.-B. Luo et al. / Tetrahedron: Asymmetry 22 (2011) 2117–2123
2121
4.2.9. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(4-
methoxyphenyl)-2-propenoate 7i
1H), 7.51 (d, J = 6.0 Hz, 1H), 7.58 (d, J = 1.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 14.2, 25.4 (d, J = 138 Hz), 52.6 (d, J = 7 Hz),
61.2, 112.1, 116.7, 119.0 (d, J = 13 Hz), 127.2 (d, J = 11 Hz), 144.8,
150.8 (d, J = 4 Hz), 167.0; 31P NMR (162 MHz, CDCl3): d 28.9. HRMS
(ESI): calcd for C12H17O6P [M+Na]+: 311.0660, found: 311.0664.
Yield: 56%. Oil. 1H NMR (400 MHz, CDCl3): d 1.36 (t, J = 7.1 Hz,
3H), 3.26 (d, J = 22.3 Hz, 2H), 3.73 (d, J = 10.8 Hz, 6H), 3.82 (s,
3H), 4.30 (q, J = 7.0 Hz, 2H), 6.95 (d, J = 8.6 Hz, 2H), 7.58 (d,
J = 8.4 Hz, 2H), 7.78 (d, J = 5.1 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 14.3, 25.4 (d, J = 140 Hz), 52.8 (d, J = 5 Hz), 55.3, 61.2, 114.1, 121.2
(d, J = 11 Hz), 127.2, 131.4, 141.4 (d, J = 11 Hz), 160.3, 167.7; 31P
NMR (162 MHz, CDCl3): d 29.2. HRMS (ESI): calcd for C15H21O6P
[M+Na]+: 351.0973, found: 351.0987.
4.2.15. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(2-thienyl)-2-
propenoate 7o
Yield: 48%. Oil. 1H NMR (400 MHz, CDCl3): d 1.36 (t, J = 7.1 Hz,
3H), 3.39 (d, J = 22.5 Hz, 2H), 3.72 (d, J = 11.0 Hz, 6H), 4.29 (q,
J = 7.1 Hz, 2H), 7.11 (t, J = 4.4 Hz, 1H), 7.45 (s, 1H), 7.52 (d,
J = 4.9 Hz, 1H), 7.92 (d, J = 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 14.3, 26.2 (d, J = 140 Hz), 52.8 (d, J = 6 Hz), 61.3, 119.7 (d,
J = 13 Hz), 127.6, 129.6, 132,6, 133.6 (d, J = 11 Hz), 137.7 (d,
J = 4 Hz), 167.1; 31P NMR (162 MHz, CDCl3): d 28.2. HRMS (ESI):
calcd for C12H17O5PS [M+Na]+: 327.0432, found: 327.0438.
4.2.10. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(3-
methoxyphenyl)-2-propenoate 7j
Yield: 62%. Oil. 1H NMR (400 MHz, CDCl3): d 1.37 (t, J = 7.1 Hz,
3H), 3.24 (d, J = 22.6 Hz, 2H), 3.73 (d, J = 10.8 Hz, 6H), 3.84 (s,
3H), 4.31 (q, J = 7.1 Hz, 2H), 6.91 (dd, J = 8.1, 1.6 Hz, 1H), 7.10 (d,
J = 7.5 Hz, 1H), 7.20 (s, 1H), 7.32 (t, J = 7.9 Hz, 1H), 7.80 (d,
J = 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 14.2, 25.4 (d,
J = 140 Hz), 52.7 (d, J = 7 Hz), 55.4, 61.3, 114.0, 115.2, 121.7, 123.9
(d, J = 11 Hz), 129.6, 136.1, 141.6 (d, J = 11 Hz), 159.7, 167.3; 31P
NMR (162 MHz, CDCl3): d 29.0. HRMS (ESI): calcd for C15H21O6P
[M+Na]+: 351.0973, found: 351.0979.
4.2.16. Ethyl 2-[(dimethoxyphosphoryl)methyl]-2-propenoate
7p9
Yield: 30%. Oil. 1H NMR (400 MHz, CDCl3): d 1.32 (t, J = 7.1 Hz,
3H), 2.97 (d, J = 22.1 Hz, 2H), 3.75 (d, J = 10.9 Hz, 6H), 4.25 (q,
J = 7.1 Hz, 2H), 5.87 (d, J = 5.4 Hz, 1H), 6.37 (d, J = 5.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3): d 14.1, 27.6 (d, J = 139 Hz), 52.8 (d,
J = 7 Hz), 61.3, 128.8 (d, J = 9 Hz), 131.2 (d, J = 11 Hz), 166.0 (d,
J = 5 Hz), 167.4; 31P NMR (162 MHz, CDCl3): d 28.8.
4.2.11. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(2-
methoxyphenyl)-2-propenoate 7k
Yield: 49%. White crystal, mp: 95–96 °C. 1H NMR (400 MHz,
CDCl3): d 1.37 (t, J = 7.2 Hz, 3H), 3.18 (d, J = 22.4 Hz, 2H), 3.69
(dd, J = 10.8, 2.0 Hz, 6H), 3.85 (s, 3H), 4.31 (q, J = 7.2 Hz, 2H), 6.91
(d, J = 8.4 Hz, 1H), 7.01 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H),
7.66 (d, J = 7.6 Hz, 1H), 7.94 (d, J = 5.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 14.3, 25.4 (d, J = 140 Hz), 52.7 (d, J = 7 Hz),
55.5, 61.2, 110.5, 120.6, 123.8 (d, J = 11 Hz), 129.9, 130.5, 137.9
(d, J = 12 Hz), 157.4, 167.4; 31P NMR (162 MHz, CDCl3): d 29.4.
4.2.17. Ethyl 2-[(dimethoxyphosphoryl)methyl]-4-methyl-2-
pentenoate 7q
Yield: 63%. Oil. 1H NMR (400 MHz, CDCl3): d 1.06 (d, J = 6.6 Hz,
6H), 1.32 (t, J = 7.1 Hz, 3H), 2.71 (m, 1H), 3.00 (d, J = 22.1 Hz, 2H),
3.73 (d, J = 10.9 Hz, 6H), 4.23 (q, J = 7.1 Hz, 2H), 6.72 (d,
J = 10.5 Hz, 5.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 14.2, 21.6,
23.8 (d, J = 139 Hz), 28.6, 52.6 (d, J = 6 Hz), 60.9, 120.3 (d,
J = 9 Hz), 152.1 (d, J = 10 Hz), 166.9; 31P NMR (162 MHz, CDCl3): d
29.2. HRMS (ESI): calcd for C11H21O5P [M+Na]+: 287.1024, found:
287.1026.
HRMS (ESI): calcd for
351.0979.
C
15H21O6P [M+Na]+: 351.0973, found:
4.2.12. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(3-
chlorophenyl)-2-propenoate 7l
4.3. General hydrogenation procedure
Yield: 59%. Oil. 1H NMR (400 MHz, CDCl3): d 1.37 (t, J = 7.1 Hz,
3H), 3.19 (d, J = 22.6 Hz, 2H), 3.74 (dd, J = 11.0, 6H), 4.32 (q,
J = 7.1 Hz, 2H), 7.34 (m, 2H), 7.47 (d, J = 7.1 Hz, 1H), 7.57 (s, 1H),
7.74 (d, J = 5.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 14.2, 25.2
(d, J = 140 Hz), 52.7 (d, J = 7 Hz), 61.4, 125.2 (d, J = 11 Hz), 127.2,
128.8, 129.0, 129.9, 134.4, 136.5 (d, J = 2 Hz), 139.8 (d, J = 11 Hz),
166.8; 31P NMR (162 MHz, CDCl3): d 28.4. HRMS (ESI): calcd for
To a solution of [Rh(COD)2]SbF6 (2.8 mg, 0.005 mmol) in anhy-
drous and degassed CH2Cl2 (1 mL), which was placed in a nitro-
gen-filled glovebox, was added TaniaPhos (0.0055 mmol). The
reaction mixture was stirred at room temperature for 30 min,
and then a solution of the unsaturated ester (0.5 mmol) in 1 mL
of CH2Cl2 was added. The mixture was transferred to a Par stainless
autoclave. The autoclave was purged three times with hydrogen,
and a hydrogen pressure of 10 bar maintained. The hydrogenation
was performed at room temperature for 24 h. After carefully
releasing the hydrogen gas, the solvent was removed. Conversion
was directly determined by 1H NMR spectroscopy. The enantio-
meric excess was determined by HPLC after purification on silica
gel.
C
14H18ClO5P [M+Na]+: 355.0478, found: 355.0492.
4.2.13. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(2-
chlorophenyl)-2-propenoate 7m
Yield: 63%. Oil. 1H NMR (400 MHz, CDCl3): d 1.38 (t, J = 7.2 Hz,
3H), 3.11 (d, J = 22.8 Hz, 2H), 3.69 (d, J = 10.8, 6H), 4.33 (q,
J = 7.2 Hz, 2H), 7.32 (m, 2H), 7.43 (d, J = 7.2 Hz, 1H), 7.68 (dd,
J = 7.2 Hz, 2.0 Hz, 1H), 7.874 (d, J = 5.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 14.2, 25.02 (d, J = 139 Hz), 52.6 (d, J = 6 Hz),
61.4, 125.8 (d, J = 11 Hz), 126.9, 129.5, 129.9, 130.1, 133.4 (d,
J = 3 Hz), 133.8, 138.6 (d, J = 11 Hz), 166.7; 31P NMR (162 MHz,
CDCl3): d 28.6. HRMS (ESI): calcd for C14H18ClO5P [M+Na]+:
355.0478, found: 355.0480.
4.3.1. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-phenyl-2-
propionate 8a
96% ee. HPLC conditions: chiralcel OD-H, 40 °C, 215 nm, n-hex-
ane/i-propanol = 94/6, flow rate = 1.0 mL/min; ½a D20
¼ þ16:8 (c 1.3,
ꢀ
CHCl3); 1H NMR (400 MHz, CDCl3): d 1.15 (t, J = 7.1 Hz, 3H), 1.83–
1.92 (m, 1H), 2.23 (m, 1H), 2.86 (m, 1H), 2.98 (m, 2H), 3.68 (m,
6H), 4.08 (q, J = 7.1 Hz, 2H), 7.16 (d, J = 7.4 Hz, 2H), 7.22 (d,
J = 6.8 Hz, 1H), 7.28 (t, J = 7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 14.0, 26.0 (d, J = 141 Hz), 39.5 (d, J = 14 Hz), 41.8 (d, J = 3 Hz),
52.3 (d, J = 7 Hz), 52.4 (d, J = 6 Hz), 60.8, 126.8, 128.5, 129.0,
137.8, 174.0 (d, J = 7 Hz); 31P NMR (162 MHz, CDCl3): d 32.0. HRMS
(ESI): calcd for C14H21O5P [M+Na]+: 323.1024, found: 323.1019.
4.2.14. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(2-furyl)-2-
propenoate 7n
Yield: 63%. Oil. 1H NMR (400 MHz, CDCl3): d 1.35 (t, J = 7.2 Hz,
3H), 3.54 (d, J = 23.6 Hz, 2H), 3.69 (d, J = 10.9 Hz, 6H), 4.28 (q,
J = 7.2 Hz, 2H), 6.51 (dd, J = 3.6, 2.0 Hz, 1H), 6.75 (d, J = 1.6 Hz,

2122
L.-B. Luo et al. / Tetrahedron: Asymmetry 22 (2011) 2117–2123
4.3.2. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(4-
fluorophenyl)-2-propionate 8f
4.3.7. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(2-
methoxyphenyl)-2-propionate 8k
91% ee. HPLC conditions: chiralcel OD-H, 40 °C, 215 nm, n-hex-
97% ee. HPLC conditions: chiralcel OJ-H, 40 °C, 215 nm, n-hex-
ane/i-propanol = 94/6, flow rate = 1.0 mL/min; ½a D20
ꢀ
¼ þ17:9 (c 1.4,
ane/i-propanol = 95/5, flow rate = 1.0 mL/min;
½
a 2D0
ꢀ
¼ þ27:9 (c
CHCl3); 1H NMR (400 MHz, CDCl3): d 1.16 (t, J = 7.1 Hz, 3H), 1.82–
1.92 (m, 1H), 2.22 (m, 1H), 2.88 (m, 1H), 2.98 (m, 2H), 3.70 (dd,
J = 10.9, 2.6 Hz, 6H), 4.07 (q, J = 7.1 Hz, 2H), 6.97 (m, 2H), 7.13 (m,
2H); 13C NMR (100 MHz, CDCl3): d 14.0, 26.1 (d, J = 142 Hz), 38.6
(d, J = 13 Hz), 41.8, 52.3 (d, J = 7 Hz), 52.5, 60.8, 115.1, 115.4,
130.5 (d, J = 7 Hz), 133.5, 160.5, 163.0, 173.8 (d, J = 7 Hz); 31P
NMR (162 MHz, CDCl3): d 31.8. HRMS (ESI): calcd for C14H20FO5P
[M+Na]+: 341.0930, found: 341.0923.
1.1, CHCl3); 1H NMR (400 MHz, CDCl3): d 1.14 (t, J = 7.2 Hz, 3H),
1.87 (m, 1H), 2.24 (m, 1H), 2.91 (m, 2H), 3.11 (m, 1H), 3.66 (dd,
J = 10.6, 9.0 Hz, 6H), 3.82 (s, 3H), 4.06 (dq, J = 7.1, 2.4 Hz, 2H),
6.85 (m, 2H), 7.06 (d, J = 7.1 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3): d 14.1, 26.3 (d, J = 140 Hz), 34.9 (d,
J = 15 Hz), 40.0, 52.2 (d, J = 6 Hz), 52.4 (d, J = 6 Hz), 55.2, 60.6,
110.3, 120.3, 126.1, 128.2, 130.9, 157.6, 174.4 (d, J = 4 Hz); 31P
NMR (162 MHz, CDCl3): d 32.5. HRMS (ESI): calcd for C15H23O6P
[M+Na]+: 353.1130, found: 353.1122.
4.3.3. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(4-
chlorophenyl)-2-propionate 8g
4.3.8. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(3-
chlorophenyl)-2-propionate 8l
96% ee. HPLC conditions: chiralcel OD-H, 40 °C, 215 nm, n-hex-
ane/i-propanol = 95/5, flow rate = 1.0 mL/min; ½a D20
ꢀ
¼ þ21:1 (c 1.2,
92% ee. HPLC conditions: chiralcel OD-H, 40 °C, 215 nm, n-hex-
CHCl3); 1H NMR (400 MHz, CDCl3): d 1.16 (t, J = 7.1 Hz, 3H), 1.82–
1.91 (m, 1H), 2.17–2.28 (m, 1H), 2.85–2.98 (m, 3H), 3.71 (d,
J = 10.7 Hz, 6H), 3.78 (s, 3H), 4.08 (q, J = 7.0 Hz, 2H), 7.10 (d,
J = 8.1 Hz, 2H), 7.25 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 14.1, 26.2 (d, J = 142 Hz), 38.7 (d, J = 13 Hz), 41.7, 52.4, 52.5 (d,
J = 7 Hz), 60.9, 128.6, 130.4, 132.6, 136.3, 173.7 (d, J = 7 Hz); 31P
NMR (162 MHz, CDCl3): d 31.8. HRMS (ESI): calcd for C14H20ClO5P
[M+Na]+: 357.0635, found: 357.0621.
ane/i-propanol = 95/5, flow rate = 1.0 mL/min; ½a D20
¼ þ17:1 (c 1.2,
ꢀ
CHCl3); 1H NMR (400 MHz, CDCl3): d 1.16 (t, J = 7.1 Hz, 3H), 1.82–
1.92 (m, 1H), 2.18–2.25 (m, 1H), 2.87–3.00 (m, 3H), 3.71 (dd,
J = 10.9 Hz, 3.2 Hz, 6H), 3.78 (s, 3H), 4.09 (q, J = 7.0 Hz, 2H), 7.06
(m, 1H),7.17 (s, 1H), 7.21 (m, 2H); 13C NMR (100 MHz, CDCl3): d
14.0, 26.2 (d, J = 141 Hz), 39.0 (d, J = 13 Hz), 41.6 (d, J = 2 Hz),
52.3, 52.5 (d, J = 7 Hz), 60.9, 127.0, 127.3, 129.2, 129.7, 134.2,
139.9, 173.6 (d, J = 8 Hz); 31P NMR (162 MHz, CDCl3): d 31.6. HRMS
(ESI): calcd for C14H20ClO5P [M+Na]+: 357.0635, found: 357.0619.
4.3.4. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(4-
nitrophenyl)-2-propionate 8h
4.3.9. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(2-furyl)-2-
propionate 8n
95% ee. HPLC conditions: chiralcel OJ-H, 40 °C, 215 nm, n-hex-
ane/i-propanol = 90/10, flow rate = 1.0 mL/min; ½a D20
ꢀ
¼ þ23:7 (c
90% ee. HPLC conditions: chiralpak AD-H, 40 °C, 215 nm, n-hex-
1.1, CHCl3); 1H NMR (400 MHz, CDCl3): d 1.16 (t, J = 7.2 Hz, 3H),
1.87–1.96 (m, 1H), 2.21–2.32 (m, 1H), 3.07 (m, 3H), 3.74 (d,
J = 10.9 Hz, 6H), 3.78 (s, 3H), 4.08 (dq, J = 7.1, 3.7 Hz, 2H), 7.38 (d,
J = 8.5 Hz, 2H), 8.16 (d, J = 8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 14.0, 26.5 (d, J = 142 Hz), 38.7 (d, J = 11 Hz), 41.4 (d, J = 2 Hz),
52.5, 52.6 (d, J = 7 Hz), 61.1, 123.7, 130.3, 145.8, 146.9, 173.2 (d,
J = 9 Hz); 31P NMR (162 MHz, CDCl3): d 31.1. HRMS (ESI): calcd
for C14H20NO7P [M+Na]+: 368.0875, found: 368.0871.
ane/i-propanol = 95/5, flow rate = 1.0 mL/min; ½a D20
¼ þ10:6 (c 1.1,
ꢀ
CHCl3); 1H NMR (400 MHz, CDCl3): d 1.23 (t, J = 7.1 Hz, 3H), 1.87–
1.97 (m, 1H), 2.21–2.31 (m, 1H), 2.95–3.11 (m, 3H), 3.71 (d,
J = 10.9 Hz, 6H), 3.82 (s, 3H), 4.14 (q, J = 7.0 Hz, 2H), 6.07 (s, 1H),
6.27 (s, 1H), 7.31 (s, 1H); 13C NMR (100 MHz, CDCl3): d 14.1, 25.8
(d, J = 142 Hz), 31.5 (d, J = 13 Hz), 39.3, 52.3 (d, J = 7 Hz), 52.4 (d,
J = 7 Hz), 61.0, 107.4, 110.2, 141.8, 151.7, 173.6 (d, J = 8 Hz); 31P
NMR (162 MHz, CDCl3): d 31.9. HRMS (ESI): calcd for C12H19O6P
[M+Na]+: 313.0841, found: 313.0827.
4.3.5. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(4-
methoxyphenyl)-2-propionate 8i
4.3.10. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(2-thienyl)-2-
propionate 8o
95% ee. HPLC conditions: chiralcel OJ-H, 40 °C, 215 nm, n-hex-
ane/i-propanol = 95/5, flow rate = 1.0 mL/min; ½a D20
ꢀ
: 21.5 (c 1.2,
98% ee. HPLC conditions: chiralcel OD-H, 40 °C, 215 nm, n-hex-
CHCl3); 1H NMR (400 MHz, CDCl3): d 1.17 (t, J = 7.1 Hz, 3H), 1.82–
1.91 (m, 1H), 2.19 (m, 1H), 2.80 (m, 1H), 2.92 (m, 2H), 3.70 (dd,
J = 10.9, 2.6 Hz, 6H), 3.77 (s, 3H), 4.09 (q, J = 7.1 Hz, 2H), 6.82 (d,
J = 8.2 Hz, 2H), 7.07 (J = 8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d
14.0, 25.9 (d, J = 141 Hz), 38.6 (d, J = 14 Hz), 41.9 (d, J = 3 Hz),
52.3 (d, J = 7 Hz), 52.4 (d, J = 7 Hz), 55.2, 60.7, 113.8, 129.7, 130.0,
158.4, 174.0 (d, J = 6 Hz); 31P NMR (162 MHz, CDCl3): d 32.2. HRMS
(ESI): calcd for C15H23O6P [M+Na]+: 353.1130, found: 353.1115.
ane/i-propanol = 94/6, flow rate = 1.0 mL/min; ½a D20
¼ þ13:1 (c 1.2,
ꢀ
CHCl3); 1H NMR (400 MHz, CDCl3): d 1.23 (t, J = 7.1 Hz, 3H), 1.94
(m, 1H), 2.19–2.26 (m, 1H), 3.03 (m, 1H), 3.12–3.26 (m, 2H), 3.71
(dd, J = 10.7, 1.9 Hz, 6H), 4.14 (q, J = 7.2 Hz, 2H), 6.83 (d,
J = 3.2 Hz, 1H), 6.91 (dd, J = 5.0, 3.5 Hz, 1H), 7.15 (d, J = 5.1 Hz,
1H); 13C NMR (100 MHz, CDCl3): d 14.1, 25.7 (d, J = 142 Hz), 33.1
(d, J = 12 Hz), 42.0, 52.5, 61.1, 124.4, 126.4, 126.9, 139.7, 173.5 (d,
J = 7 Hz); 31P NMR (162 MHz, CDCl3): d 32.0. HRMS (ESI): calcd
for C12H19O5PS [M+Na]+: 329.0589, found: 329.0584.
4.3.6. Ethyl 2-[(dimethoxyphosphoryl)methyl]-3-(3-
methoxyphenyl)-2-propionate 8j
Acknowledgments
95% ee. HPLC conditions: chiralpak AD-H, 40 °C, 215 nm, n-hex-
ane/i-propanol = 90/10, flow rate = 1.0 mL/min; ½a D20
ꢀ
¼ þ18:8 (c
We are grateful to the generous financial support from the Na-
tional Natural Science Foundation of China (20802076 and
30971936), Program for New Century Excellent Talents in Univer-
sity (NCET-10-0163) and the Knowledge Innovation Program of the
Chinese Academy of Sciences.
1.2, CHCl3); 1H NMR (400 MHz, CDCl3): d 1.18 (t, J = 7.2 Hz, 3H),
1.84–1.93 (m, 1H), 2.18–2.24 (m, 1H), 2.81–2.86 (m, 1H), 2.95–
3.00 (m, 2H), 3.69 (dd, J = 10.8, 6.4 Hz, 6H), 3.78 (s, 3H), 4.10 (q,
J = 6.8 Hz, 2H), 6.71 (s, 1H), 7.76 (m, 2H), 7.20 (t, J = 8.0 Hz, 1H);
13C NMR (100 MHz, CDCl3): d 14.1, 26.0 (d, J = 141 Hz), 39.5 (d,
J = 14 Hz), 41.7, 52.3 (d, J = 6 Hz), 52.4 (d, J = 6 Hz), 55.2, 60.8,
112.2, 114.7, 121.4, 129.5, 139.3, 159.7, 174.0 (d, J = 6 Hz); 31P
NMR (162 MHz, CDCl3): d 32.1. HRMS (ESI): calcd for C15H23O6P
[M+Na]+: 353.1130, found: 353.1121.
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