Enantioselective synthesis of optically active alkylphosphonates via Rh-catalyzed asymmetric hydrogenation of β-substituted α,β- unsaturated phosphonates

Article abstract of DOI:10.1016/j.tetasy.2012.03.024

The Rh-catalyzed asymmetric hydrogenation of β-substituted α,β-unsaturated phosphonates using (S_c,S _p)-WalPhos as the chiral ligand is reported, in which a wide range of optically active β-substituted alkylphosphonates were obtained

Full text of DOI:10.1016/j.tetasy.2012.03.024

Tetrahedron: Asymmetry 23 (2012) 508–514
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Tetrahedron: Asymmetry
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Enantioselective synthesis of optically active alkylphosphonates via
Rh-catalyzed asymmetric hydrogenation of b-substituted
a,b-unsaturated
phosphonates
Zheng-chao Duan a, , Lian-zhi Wang a, Xin-jian Song a, Xiang-ping Hu b, , Zhuo Zheng b
⇑
⇑
a Hubei University for Nationalities, Enshi 445000, 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:
The Rh-catalyzed asymmetric hydrogenation of b-substituted
a,b-unsaturated phosphonates using
(Sc,Sp)-WalPhos as the chiral ligand is reported, in which a wide range of optically active b-substituted
alkylphosphonates were obtained in good yields and with good to excellent enantioselectivities (86–
98% ee). In contrast to the Rh/(Rc,Sa)-FAPhos system previously reported by us, the present catalytic sys-
tem shows a wider substrate scope, and can perform the hydrogenation under milder reaction conditions.
Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
1. Introduction
O
OEt
O
P
Optically active alkylphosphonic acid derivatives have recently
received significant attention for their interesting biological prop-
erties as phosphorus analogues of carboxylic acids,1 as well as their
synthetic utilities as chiral building blocks.2 Over the past decades,
some stoichiometric and catalytic asymmetric syntheses have been
developed for constructing chiral 1-arylethylphosphonates.3 How-
ever, the enantioselective synthesis of chiral b-substituted
alkylphosphonates by a catalytic method is still rarely explored.4
In 1999, Hayashi et al. described the enantioselective synthesis of
chiral b-aryl substituted alkylphosphonates via catalytic asymmet-
ric 1,4-addition to 1-alkenylphosphonates using a chiral phos-
phine-Rh catalyst and arylboroxines as the arylating reagents.5
Considering its inherent efficiency and atom economy, we surmised
that the catalytic asymmetric hydrogenation should be a powerful
tool for the synthesis of chiral phosphonate derivatives.6 With this
strategy, we have recently developed several new synthetic meth-
ods via the Rh-catalyzed asymmetric hydrogenation of the corre-
OEt
N
P
O
Fe
74% conversion under 40 atm
of H2 pressure and 50 o
C
with Rh/(Rc,Sa)-FAPhos catalyst
(Rc,Sa)-FAPhos
P(O)(OEt)2
P(O)(OEt)2
35% conversion and 57% ee
under 40 atm of H2 pressure
with Rh/(Rc,Sa)-FAPhos catalyst
84% ee under 40 atm of H2 pressure
with Rh/(Rc,Sa)-FAPhos catalyst
Figure 1. The structure of (Rc,Sa)-FAPhos and some challenging substrates with the
Rh/FAPhos catalytic system.
sponding b-substituted
substituted b,
-unsaturated phosphonates.8 Excellent enantiose-
lectivities have been achieved in the Rh-catalyzed asymmetric
hydrogenation of b-substituted ,b-unsaturated phosphonates by
a
,b-unsaturated phosphonates7 and b-
c
40 atm of hydrogen pressure for complete conversion. Further-
more, the Rh/(Rc,Sa)-FAPhos catalytic system gave low conversions
or low enantioselectivity in the hydrogenation of some substrates,
such as (E)-diethyl 2-o-tolylprop-1-enylphosphonate, (E)-diethyl
a
employing
a chiral ferrocenyl monophosphoramidite ligand,
(Rc,Sa)-FAPhos (Fig. 1).7 However, the hydrogenation conditions
with the Rh/(Rc,Sa)-FAPhos system were harsh, normally requiring
2-phenylpent-1-enylphosphonate,
and
(E)-diethyl
(2,3-
dihydronaphthalen-4(1H)-ylidene)methylphosphonate even under
an elevated hydrogenation temperature and pressure (Fig. 1).
The shortcomings of the Rh/(Rc,Sa)-FAPhos catalytic system
prompted us to search for a more reactive and enantioselective cat-
alyst for the Rh-catalyzed asymmetric hydrogenation of b-substi-
⇑
Corresponding authors. Tel.: +86 718 8437531; fax: +86 718 8437531
(Z.-c.D.).
E-mail addresses: dzhch168@163.com (Z.-c. Duan), xiangping@dicp.ac.cn
(X.-p. Hu).
tuted
a,b-unsaturated phosphonates. As a result, we herein
0957-4166/$ - see front matter Crown Copyright Ó 2012 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.03.024

Z. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 508–514
509
Table 1
report that the commercially available bidentate phosphorus li-
gand, (Sc,Sp)-WalPhos, was identified as the optimal ligand for
the Rh-catalyzed asymmetric hydrogenation of b-substituted ,b-
unsaturated phosphonates, providing various chiral b-substituted
alkylphosphonates in good yields and with good to high enantiose-
lectivities under mild hydrogenation condition.
Asymmetric hydrogenation of diethyl (E)-(2-phenyl-1-propenyl)phosphonate 1aa
[Rh(COD)2]BF4 (1 mol%)
chiral ligand
a
O
P
O
P
OEt
OEt
OEt
OEt
∗
Ph
H2, solvent, rt
Ph
(E)-1a
Ligand
2a
Entry
Solvent
Conv.b (%)
eec (%)
2. Results and discussion
d
1
2
3
4
5
6
(R,R)-Me-DuPhos
(S)-BINAP
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
i-PrOH
MeOH
THF
—
84
—
30 (S)
75 (R)
54 (R)
93 (R)
94 (R)
93 (R)
92 (R)
82 (R)
86 (R)
88 (R)
87 (R)
(Sc,Rp)-Me-BoPhoz
(Sc,Sp)-TaniaPhos
(Sc,Sp)-WalPhos
(Rc,Sp)-WalPhos
(Sc,Sp)-WalPhos
(Rc,Sp)-WalPhos
(Sc,Sp)-WalPhos
(Sc,Sp)-WalPhos
(Sc,Sp)-WalPhos
(Sc,Sp)-WalPhos
100
100
100
100
100
56
We have previously reported that some bidentate phosphorus
ligands such as Me-Duphos, BINAP and Bophoz, give unsatisfactory
results in the Rh-catalyzed asymmetric hydrogenation of b-substi-
tuted a
,b-unsaturated phosphonates.7 In an attempt to search for a
7e
8f
9
10
11
12
more effective ligand, we focused our studies on screening ferro-
cene-based bidentate ligands such as TaniaPhos9 and WalPhos10
(Fig. 2) because of their demonstrated track record at effecting
Rh-catalyzed asymmetric hydrogenations. Initially, (E)-1a was se-
lected as the model substrate, and the hydrogenation was per-
formed under 10 atm of H2 pressure in CH2Cl2 for 24 h. The
results (Table 1) showed that the Rh/Taniaphos complex displayed
high reactivity, but low enantioselectivity (entry 4). We found that
(Sc,Sp)-WalPhos exhibited excellent results, in which full conver-
sion and 93% ee were obtained (entry 5). Similar results were
achieved when (Rc,Sp)-WalPhos was used (entry 6). These results
showed that the central chirality in this ligand type was not so
important in order to induce high enantioselectivity. The Rh/
(Sc,Sp)-WalPhos proved to be highly efficient for this hydrogena-
tion, in which full conversion and high enantioselectivity were ob-
tained even at a catalyst loading as low as 0.1 mol % (entry 7).
However, the corresponding (Rc,Sp)-WalPhos only provided 56%
conversion even under a hydrogen pressure of 40 atm (entry 8).
We therefore identified (Sc,Sp)-WalPhos as the optimal ligand for
this hydrogenation. Solvent screening suggested that the nature
of the solvent had some effect on the reactivity and enantioselec-
tivity. However, no results surpassed those obtained in CH2Cl2.
For example, although the reactions in MeOH, THF, and i-PrOH
gave full conversion, ee-values were lower than those obtained
in CH2Cl2 (entries 10–12). When the hydrogenation was per-
formed in toluene, a decreased conversion of 89% was observed
(entry 9).
89
100
100
100
a
The reactions were carried out with 0.25 mmol of substrate at room tempera-
ture under an H2 pressure of 10 atm in 2 mL of the indicated solvent for 24 h.
b
Degrees of conversion were determined by GC.
The ee values were determined by HPLC on a chiral column.
Not determined because of low conversion.
c
d
e
The reaction was performed at 20 atm hydrogen pressure and 0.1% catalyst
loading.
f
The reaction was performed at 40 atm hydrogen pressure and 0.1% catalyst
loading.
Table 2
Asymmetric hydrogenation of diethyl (E)-(2-aryl-1-propenyl)phosphonates 1a–na
Rh(COD)2BF4 (1 mol%)
(Sc,Sp)-Walphos (1.1 mol%)
O
P
O
P
OEt
OEt
OEt
OEt
∗
Ar
Ar
H2 (10atm), CH2Cl2, RT
2
1
(E)-
Entry
Substrate
Ar
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
Ph
98
93
96
98
95
98
96
98
98
97
98
94
98
98
93 (R)
87 (+)
94 (+)
94 (+)
86 (+)
94 (+)
94 (+)
92 (+)
93 (+)
94 (+)
94 (+)
95 (+)
91 (+)
98 (+)
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
2-MeC6H4
3-MeC6H4
4-MeC6H4
3-CF3C6H4
4-CF3C6H4
4-FC6H4
With these encouraging results in the hydrogenation of (E)-1a,
we proceeded to investigate the scope of this transformation on
9
various b-substituted
a,b-unsaturated phosphonates 1a–s, using
10
11
12
13
14
(Sc,Sp)-WalPhos as the ligand and CH2Cl2 as the solvent under a
hydrogen pressure of 10 atm at room temperature for 24 h. As
shown in Table 2, a wide range of b-aryl-a,b-unsaturated phospho-
4-ClC6H4
4-BrC6H4
2-Naphthyl
2-Thiophenyl
nates (E)-1a–1l were hydrogenated to provide the corresponding
2-arylpropylphosphonates with good yields and high enantioselec-
tivities (up to 94% ee). The results indicated that the present cata-
lytic system has a high tolerance with regard to the electronic
properties of the substituent on the phenyl ring in terms of reactiv-
ity and enantioselectivity. However, the substitution pattern of the
substituent on the phenyl ring had some effect on the enantiose-
lectivity; the ortho-substituted substrates tended to give lower
enantioselectivities than their meta- and para-analogues. Thus,
a
All reactions were carried out with 0.25 mmol of substrate at room temperature
under a H2 pressure of 10 atm in 2 mL of CH2Cl2 for 24 h. Substrate/Rh(COD)2BF4/
ligand = 1/0.01/0.011.
b
Isolated yields.
c
The ee values were determined by HPLC on a chiral column (Chiralpak AD-H or
OJ-H). The absolute configuration was determined by comparing the specific rota-
tion with the reported data.
the hydrogenation of 3- and 4-methoxy substituted substrates
gave ee-values of 94% ee (entries 3 and 4), while the hydrogenation
of the corresponding 2-methoxy substituted one only provided
87% ee (entry 2). The reason for this is presumably due to the steric
hindrance of the ortho-substituent. Although relatively low enanti-
oselectivities were obtained for ortho-substituted substrates, it
should be noted that these results represented progress in contrast
to that reported recently with an Rh/(Rc,Sa)-FAPhos catalyst. With
the Rh/(Rc,Sa)-FAPhos catalyst, incomplete conversion was
achieved even at higher hydrogenation temperatures (50 °C) and
higher hydrogenation pressure (40 atm).7 Diethyl (E)-[2-(2-naph-
Ph2P
Me2N
PPh2
PPh2
PPh2
PPh2
PPh2
Fe
Fe
Fe
(Rc,Sp)-WalPhos
(Sc,Sp)-WalPhos
TaniaPhos
Figure 2. Ligands for the asymmetric hydrogenation.

510
Z. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 508–514
thyl)-1-propenyl]phosphonate 1m was a suitable substrate, giving
the hydrogenation product 2m in 98% yield and 91% ee (entry 13).
(S)-Heteroaromatic substrate 1n was also a good substrate for this
hydrogenation, affording the hydrogenation product in with 98%
yields and 98% ee (entry 14). These results demonstrated the effi-
ciency of the present catalytic system in the hydrogenation of b-
3. Conclusion
In conclusion, we have identified that (Sc,Sp)-WalPhos is a suit-
able ligand for the Rh-catalyzed asymmetric hydrogenation of b-
substituted
a,b-unsaturated phosphonates, in which good yields
and up to 98% ee were obtained for a wide range of substrates un-
der mild hydrogenation conditions. This catalytic system is poten-
tially practical for the synthesis of optically active b-substituted
alkylphosphonates. The development of new catalytic methods to
synthesize chiral alkylphosphonates is still in progress.
aryl substituted
To further illustrate the synthetic interest in this highly enan-
tioselective procedure, a series of structurally diverse ,b-unsatu-
a,b-unsaturated phosphonates.
a
rated phosphonates (Fig. 3), including those that were less
efficient substrates with the Rh/(Rc,Sa)-FAPhos catalyst, were sub-
mitted to this hydrogenation under the optimized hydrogenation
conditions, and the results are summarized in Table 3.
4. Experimental
4.1. General methods
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
(EtO)2(O)P
All reactions and manipulations were performed in a nitrogen-
filled glove-box or under nitrogen using Schlenk techniques unless
otherwise noted. All solvents were distilled under argon in the
presence of the following desiccants: sodium-benzophenone-ketyl
for diethyl ether (Et2O), tetrahydrofuran (THF), CaH2 for dichloro-
methane (CH2Cl2). NMR spectra were obtained on Bruker DRX
400 spectrometers. 31P NMR shifts were referenced to external
85% H3PO4, while 13C and 1H NMR shifts were referenced to the
residual signals of deuterated solvents.
E-1o
Z-1o
E-1p
E-1s
P(O)(OEt)2
P(O)(OEt)2
MeO
E-1q
E-1r
4.2. General procedure for the preparation of b-substituted a,b-
unsaturated phosphonates
Figure 3. Substrates for the asymmetric hydrogenation.
A solution of (EtO)2P(O)CH2P(O)(OEt)2 (1.44 g, 5 mmol) in THF
(2 mL) was slowly added at 0 °C to a slurry of NaH (0.19 g,
5.5 mmol, 70% in oil) in THF (10 mL). After the addition, the mix-
ture was stirred at room temperature for 0.5 h. To the mixture, a
solution of ketone (4.25 mmol) in THF (3 mL) was added. The reac-
tion mixture was stirred at room temperature until the ketone dis-
appeared when monitored by TLC. The mixture was then diluted
with ether and washed with an aqueous solution of saturated
NH4Cl (25 mL ꢀ 1) and brine (25 mL ꢀ 1). The organic layer was
separated, and dried over anhydrous NaSO4. After removal of the
volatiles, the residue was purified by column chromatography (sil-
ica gel, AcOEt/hexane 1:1).
The results indicated that the Rh/(Sc,Sp)-WalPhos complex was
also highly efficient for the hydrogenation of b-alkyl substituted
a,b-unsaturated phosphonates such as (E)-1o, providing the hydro-
genation product in good yields and with excellent enantioselec-
tivity of 96% ee (entry 1). For the hydrogenation of the
corresponding (Z)-substrate [(Z)-1o], similar results were achieved
with the absolute configuration of the hydrogenation product
opposite to that obtained in the hydrogenation of its (E)-isomer
(entry 2). The hydrogenation of (E)-1p, (E)-1q, and (E)-1r proved
to be as efficient as in the hydrogenation of their 1-ethenylphosph-
onate analogues, giving the hydrogenation products in good yields
with ee-values of 93%, 94% and 93%, respectively (entries 3–5). The
hydrogenation of (E)-diethyl (2,3-dihydronaphthalen-4(1H)-yli-
dene)methylphos-phonate also gave the good yield and 93% ee
(entry 6). Only 57% ee and 35% conversion were achieved for the
hydrogenation of 1s, while 84% ee and full conversion for the
hydrogenation of 1r when (Rc,Sa)-FAPhos was used, even under a
hydrogen pressure of 40 atm.
4.2.1. (E)-Diethyl 2-phenylprop-1-enylphosphonate 1a7
Colorless oil, yield: 60%. 1H NMR (400 MHz, CDCl3): d 1.36 (t,
J = 7.0 Hz, 6H), 2.51 (d, J = 2.9 Hz, 3H), 4.09–4.17 (m, 4H), 5.90 (d,
J = 16.6 Hz, 1H), 7.35–7.38 (m, 3H), 7.46–7.48 (m, 2H); 13C NMR
(100 MHz, CDCl3): d 16.3, 16.4, 19.2 (d, J = 7.0 Hz), 61.4, 61.5,
113.4 (d, J = 189.0 Hz), 126.0, 128.5, 129.2, 141.8 (d, J = 23.0 Hz),
158.2 (d, J = 8.0 Hz); 31P NMR (162 MHz, CDCl3): d 18.6.
Table 3
Asymmetric hydrogenation of
a
,b-unsaturated phosphonates 1o–sa
4.2.2. (E)-Diethyl 2-(2-methoxyphenyl)prop-1-enylphosphonate
1b4
R2
∗
O
P
R2
O
P
Rh(COD)2BF4 ( 1mol%)
(Sc,Sp)-Walphos (1.1 mol%)
OEt
OEt
OEt
OEt
Colorless oil, yield: 52%. 1H NMR (400 MHz, CDCl3): d 1.36 (t,
J = 7.1 Hz, 6H), 2.44 (d, J = 3.1 Hz, 3H), 3.80 (d, J = 6.2 Hz, 3H),
4.10–4.17 (m, 4H), 5.66 (d, J = 18.7 Hz, 1H), 6.88–6.94 (m, 2H),
7.14–7.16 (m, 1H), 7.26–7.31 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 16.3, 16.4, 20.9 (d, J = 7.0 Hz), 55.4, 61.3, 61.4, 111.0, 115.9 (d,
J = 183.0 Hz), 120.5, 128.6, 129.5, 133.1 (d, J = 24.0 Hz), 156.0,
159.4 (d, J = 8.0 Hz); 31P NMR (162 MHz, CDCl3): d 18.0.
R1
R1
H2 (10atm), CH2Cl2, RT
1
2
Entry
Substrate
Yieldb (%)
eec (%)
1
2
3
4
5
6
(E)-1o
(Z)-1o
(E)-1p
(E)-1q
(E)-1r
(E)-1s
98
98
99
98
99
99
96 (+)
97 (ꢁ)
93 (+)
94 (+)
93 (+)
93 (ꢁ)
4.2.3. (E)-Diethyl 2-(3-methoxyphenyl)prop-1-enylphosphonate
1c4
a
All reactions were carried out with 0.25 mmol of substrate at room temperature
Colorless oil, yield: 58%. 1H NMR (400 MHz, CDCl3): d 1.36 (t,
J = 7.1 Hz, 6H), 2.49 (d, J = 3.2 Hz, 3H), 3.82 (s, 3H), 4.10–4.17 (m,
4H), 5.90 (d, J = 16.6 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 6.99 (s, 1H),
7.07 (d, J = 7.7 Hz, 1H), 7.26–7.30 (m, 1H); 13C NMR (100 MHz,
under an H2 pressure of 10 atm in 2 mL of CH2Cl2 for 24 h. Substrate/Rh(COD)2BF4/
ligand = 1/0.01/0.011.
b
Isolated yields.
c
The ee values were determined by HPLC on a chiral column (Chiralpak AD-H or
OJ-H).

Z. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 508–514
511
CDCl3): d 16.4, 16.5, 19.4 (d, J = 6.0 Hz), 55.3, 61.5, 61.5, 111.9,
113.7 (d, J = 189.0 Hz), 114.4, 118.5, 129.5, 143.3 (d, J = 24.0 Hz),
158.1 (d, J = 6.0 Hz), 159.6; 31P NMR (162 MHz, CDCl3): d 18.5.
137.7 (d, J = 24.0 Hz), 156.8 (d, J = 8.0 Hz), 162.0, 164.5; 31P NMR
(162 MHz, CDCl3): d 18.3.
4.2.11. (E)-Diethyl 2-(4-chlorophenyl)prop-1-enylphosphonate
1k7
4.2.4. (E)-Diethyl 2-(4-methoxyphenyl)prop-1-enylphosphonate
1d7
Colorless oil, yield: 65%. 1H NMR (400 MHz, CDCl3): d 1.36 (t,
J = 7.0 Hz, 6H), 2.48 (d, J = 2.4 Hz, 3H), 4.10–4.17 (m, 4H), 5.89 (d,
J = 16.0 Hz, 1H), 7.31–7.34 (m, 2H), 7.40–7.42 (m, 2H); 13C NMR
(100 MHz, CDCl3): d 16.4, 16.4, 19.2 (d, J = 7.0 Hz), 61.5, 61.6,
114.1 (d, J = 189.0 Hz), 127.3, 128.7, 135.1, 140.1 (d, J = 24.0 Hz),
156.6 (d, J = 8.0 Hz); 31P NMR (162 MHz, CDCl3): d 18.1.
Colorless oil, yield: 63%. 1H NMR (400 MHz, CDCl3): d 1.35 (t,
J = 7.0 Hz, 6H), 2.48 (d, J = 3.1 Hz, 3H), 3.82 (s, 3H), 4.09–4.16 (m,
4H), 5.85 (d, J = 16.5 Hz, 1H), 6.88 (d, J = 8.8 Hz, 2H), 7.45 (d,
J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 16.4, 16.4, 19.1 (d,
J = 7.0 Hz), 55.3, 61.4, 61.5, 111.1 (d, J = 191.0 Hz), 113.8, 127.4,
133.8 (d, J = 24.0 Hz), 157.4 (d, J = 8.0 Hz), 160.5; 31P NMR
(162 MHz, CDCl3): d 19.3.
4.2.12. (E)-Diethyl 2-(4-bromophenyl)prop-1-enylphosphonate
1l7
4.2.5. (E)-Diethyl 2-o-tolylprop-1-enylphosphonate 1e4
Colorless oil, yield: 45%. 1H NMR (400 MHz, CDCl3): d 1.36 (t,
J = 7.0 Hz, 6H), 2.29 (s, 3H), 2.38 (d, J = 3.2 Hz, 3H), 4.10–4.18 (m,
4H), 5.51 (d, J = 18.7 Hz, 1H), 7.06–7.08 (m, 1H), 7.14–7.19 (m,
3H); 13C NMR (100 MHz, CDCl3): d 16.4, 16.5, 19.6, 21.9 (d,
J = 6.0 Hz), 61.4, 61.5, 116.3 (d, J = 183.0 Hz), 125.8, 126.7, 127.7,
130.4, 133.3, 144.1 (d, J = 23.0 Hz), 161.2 (d, J = 6.0 Hz); 31P NMR
(162 MHz, CDCl3): d 17.4.
Colorless oil, yield: 66%. 1H NMR (400 MHz, CDCl3): d 1.33 (t,
J = 7.0 Hz, 3H), 1.35 (t, J = 7.0 Hz, 3H), 2.48 (d, J = 3.0 Hz, 3H),
4.10–4.17 (m, 4H), 5.89 (d, J = 16.0 Hz, 1H), 7.32–7.34 (m, 2H),
7.47–7.50 (m, 2H); 13C NMR (100 MHz, CDCl3): d 16.4, 16.4, 19.1
(d, J = 7.0 Hz), 61.6, 61.6, 114.2 (d, J = 190.0 Hz), 123.4, 127.6,
131.6, 140.6 (d, J = 24.0 Hz), 156.7 (d, J = 8.0 Hz); 31P NMR
(162 MHz, CDCl3): d 18.0.
4.2.13. (E)-Diethyl 2-(naphthalen-2-yl)prop-1-enylphosphonate
1m7
4.2.6. (E)-Diethyl 2-m-tolylprop-1-enylphosphonate 1f7
Colorless oil, yield: 48%. 1H NMR (400 MHz, CDCl3): d 1.35 (t,
J = 7.0 Hz, 6H), 2.36 (s, 3H), 2.50 (d, J = 3.2 Hz, 3H), 4.09–4.17 (m,
4H), 5.89 (d, J = 16.7 Hz, 1H), 7.15–7.17 (m, 1H), 7.22–7.27 (m,
3H); 13C NMR (100 MHz, CDCl3): d 16.3, 16.4, 19.3 (d, J = 7.0 Hz),
21.4, 61.4, 61.4, 113.2 (d, J = 189.0 Hz), 123.1, 126.6, 128.4, 129.9,
138.0, 141.8 (d, J = 24.0 Hz), 158.3 (d, J = 8.0 Hz); 31P NMR
(162 MHz, CDCl3): d 18.6.
Colorless oil, yield: 49%. 1H NMR (400 MHz, CDCl3): d 1.37 (t,
J = 7.1 Hz, 6H), 2.62 (d, J = 3.1 Hz, 3H), 4.12–4.19 (m, 4H), 6.06 (d,
J = 16.3 Hz, 1H), 7.46–7.48 (m, 2H), 7.56–7.59 (m, 1H), 7.78–7.84
(m, 3H), 7.91 (s, 1H); 13C NMR (100 MHz, CDCl3): d 16.4, 16.5,
19.3 (d, J = 7.0 Hz), 61.5, 61.6, 113.9 (d, J = 189.0 Hz), 123.6,
125.6, 126.6, 126.8, 127.6, 128.2, 128.5, 133.0, 133.5, 138.8 (d,
J = 24.0 Hz), 157.8 (d, J = 8.0 Hz); 31P NMR (162 MHz, CDCl3): d
18.6.
4.2.7. (E)-Diethyl 2-p-tolylprop-1-enylphosphonate 1g7
Colorless oil, yield: 61%. 1H NMR (400 MHz, CDCl3): d 1.35 (t,
J = 7.0 Hz, 6H), 2.35 (s, 3H), 2.48 (d, J = 2.7 Hz, 3H), 4.09–4.16 (m,
4H), 5.89 (d, J = 16.6 Hz, 1H), 7.16 (d, J = 8.0 Hz, 2H), 7.37 (d,
J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 16.3, 16.4, 19.1 (d,
J = 7.0 Hz), 21.1, 61.4, 61.5, 112.3 (d, J = 189.0 Hz), 125.9, 129.2,
138.7 (d, J = 23.0 Hz), 139.3, 158.0 (d, J = 8.0 Hz); 31P NMR
(162 MHz, CDCl3): d 18.9.
4.2.14. (E)-Diethyl 2-(thiophen-2-yl)prop-1-enylphosphonate
1n7
Straw yellow oil, yield: 41%. 1H NMR (400 MHz, CDCl3): d 1.35
(t, J = 7.1 Hz, 6H), 2.51 (d, J = 3.0 Hz, 3H), 4.08–4.15 (m, 4H), 5.95
(d, J = 14.3 Hz, 1H), 7.01–7.03 (m, 1H), 7.24–7.26 (m, 1H), 7.30–
7.31 (m, 1H); 13C NMR (100 MHz, CDCl3): d 16.3, 16.4, 18.8 (d,
J = 6.0 Hz), 61.4, 61.5, 110.5 (d, J = 193.0 Hz), 126.4, 127.2, 127.9,
145.4 (d, J = 27.0 Hz), 150.1 (d, J = 9.0 Hz); 31P NMR (162 MHz,
CDCl3): d 18.3.
4.2.8. (E)-Diethyl 2-[3-(trifluoromethyl)phenyl]prop-1-
enylphosphonate 1h7
Colorless oil, yield: 73%. 1H NMR (400 MHz, CDCl3): d 1.37 (t,
J = 7.1 Hz, 6H), 2.53 (d, J = 3.1 Hz, 3H), 4.11–4.18 (m, 4H), 5.94 (d,
J = 15.6 Hz, 1H), 7.48–7.52 (m, 1H), 7.61–7.66 (m, 2H), 7.69 (s,
1H); 13C NMR (100 MHz, CDCl3): d 16.3, 19.2, 61.6, 115.6 (d,
J = 190.0 Hz), 122.5, 122.8, 125.3, 125.6, 129.1, 129.3, 142.7 (d,
J = 24.0 Hz), 156.3; 31P NMR (162 MHz, CDCl3): d 17.3.
4.2.15. (E)-Diethyl 2-methyl-4-phenylbut-1-enylphosphonate
(E)-1o11
Colorless oil, yield: 53%. 1H NMR (400 MHz, CDCl3): d 1.29 (t,
J = 7.0 Hz, 6H), 2.12 (s, 3H), 2.45–2.49 (m, 2H), 2.77–2.81 (m, 2H),
3.95–4.02 (m, 4H), 5.37 (d, J = 18.3 Hz, 1H), 7.15–7.20 (m, 3H),
7.25–7.29 (m, 2H); 13C NMR (100 MHz, CDCl3): d 16.3, 16.4, 20.1
(d, J = 6.0 Hz), 33.6, 43.1 (d, J = 23.0 Hz), 61.2, 61.2, 112.2 (d,
J = 187.0 Hz), 126.1, 128.3, 128.5, 140.8, 161.9 (d, J = 5.0 Hz); 31P
NMR (162 MHz, CDCl3): d 18.5.
4.2.9. (E)-Diethyl 2-(4-(trifluoromethyl)phenyl)prop-1-
enylphosphonate 1i7
Colorless oil, yield: 75%. 1H NMR (400 MHz, CDCl3): d 1.37 (t,
J = 7.1 Hz, 6H), 2.52 (d, J = 3.1 Hz, 3H), 4.11–4.18 (m, 4H), 5.94 (d,
J = 15.7 Hz, 1H), 7.56 (d, J = 8.3 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H);
4.2.16. (Z)-Diethyl 2-methyl-4-phenylbut-1-enylphosphonate
(Z)-1o11
13C NMR (100 MHz, CDCl3):
d
16.4, 19.2, 61.6, 116.0 (d,
Colorless oil, yield: 14%. 1H NMR (400 MHz, CDCl3): d 1.30 (t,
J = 7.0 Hz, 6H), 1.94 (s, 3H), 2.77–2.85 (m, 4H), 3.99–4.06 (m, 4H),
5.41 (d, J = 18.3 Hz, 1H), 7.16–7.19 (m, 1H), 7.26–7.27 (m, 4H);
13C NMR (100 MHz, CDCl3): d 16.4, 16.5, 26.0 (d, J = 24.0 Hz),
34.7, 36.9 (d, J = 6.0 Hz), 61.2, 61.2, 113.1 (d, J = 188.0 Hz), 126.0,
128.4, 128.5, 141.4, 162.5 (d, J = 8.0 Hz); 31P NMR (162 MHz,
CDCl3): d 17.8.
J = 189.0 Hz), 125.3, 125.4, 126.4, 145.4 (d, J = 24.0 Hz), 156.5 (d,
J = 7.0 Hz); 31P NMR (162 MHz, CDCl3): d 17.3.
4.2.10. (E)-Diethyl 2-(4-fluorophenyl)prop-1-enylphosphonate
1j7
Colorless oil, yield: 68%. 1H NMR (400 MHz, CDCl3): d 1.36 (t,
J = 7.1 Hz, 6H), 2.49 (d, J = 3.0 Hz, 3H), 4.10–4.17 (m, 4H), 5.87 (d,
J = 16.1 Hz, 1H), 7.02–7.07 (m, 2H), 7.44–7.48 (m, 2H); 13C NMR
(100 MHz, CDCl3): d 16.4, 16.4, 19.3 (d, J = 7.0 Hz), 61.5, 61.5,
113.5 (d, J = 190.0 Hz), 115.4 (d, J = 22.0 Hz), 127.8 (d, J = 8.0 Hz),
4.2.17. (E)-Diethyl 2-phenylbut-1-enylphosphonate (E)-1p7
Colorless oil, yield: 30%. 1H NMR (400 MHz, CDCl3): d 1.03 (t,
J = 7.2 Hz, 3H), 1.36 (t, J = 7.2 Hz, 6H), 2.98–3.04 (m, 2H), 4.09–

512
Z. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 508–514
4.16 (m, 4H), 5.75 (d, J = 17.6 Hz, 1H), 7.35–7.38 (m, 3H), 7.40–7.43
(m, 2H); 13C NMR (100 MHz, CDCl3): d 13.5, 16.4, 16.5, 25.9 (d,
J = 7.0 Hz), 61.5, 61.6, 113.3 (d, J = 189.0 Hz), 126.5, 128.5, 129.0,
140.7 (d, J = 24.0 Hz), 166.0 (d, J = 8.0 Hz); 31P NMR (162 MHz,
CDCl3): d 18.3.
major enantiomer: tR = 25.4 min; minor enantiomer: tR = 29.6 min.
1H NMR (400 MHz, CDCl3): d 1.25 (t, J = 7.0 Hz, 6H), 1.38 (d,
J = 7.0 Hz, 3H), 1.96–2.06 (m, 1H), 2.18–2.28 (m, 1H), 3.55 (q,
J = 6.5 Hz, 1H), 3.82 (s, 3H), 3.96–4.05 (m, 4H), 6.84–6.86 (m, 1H),
6.89–6.93 (m, 1H), 7.16–7.20 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 16.3, 16.4, 21.2 (d, J = 7.0 Hz), 28.8, 32.4 (d, J = 137.0 Hz), 55.2,
61.2 (d, J = 7.0 Hz), 61.3 (d, J = 6.0 Hz), 110.6, 120.6, 127.3 (d,
J = 9.0 Hz), 134.5 (d, J = 13.0 Hz), 156.8; 31P NMR (162 MHz, CDCl3):
d 31.6. HRMS calcd for C14H23O4P: 286.1334, found 286.1335.
4.2.18. (E)-Diethyl 2-(4-methoxyphenyl)but-1-enylphosphonate
(E)-1q
Colorless oil, yield: 56%. 1H NMR (400 MHz, CDCl3): d 1.05 (t,
J = 7.2 Hz, 3H), 1.35 (t, J = 7.2 Hz, 6H), 2.95–3.00 (m, 2H), 3.83 (s,
1H), 4.09–4.16 (m, 4H), 5.71 (d, J = 16.8 Hz, 1H), 6.88–6.90 (m,
2H), 7.38–7.41 (m, 2H); 13C NMR (100 MHz, CDCl3): d 13.7, 16.4,
16.5, 25.6 (d, J = 7.0 Hz), 55.3, 61.5, 61.6, 111.1 (d, J = 190.0 Hz),
113.9, 127.9, 132.6 (d, J = 23.0 Hz), 160.4, 164.1 (d, J = 9.0 Hz); 31P
NMR (162 MHz, CDCl3): d 19.0.
4.3.3. Diethyl 2-(3-methoxyphenyl)propylphosphonate 2c5
94% ee. ½a 2D5
¼ þ19:3 (c 0.92, CHCl3). HPLC conditions: chiralcel
ꢂ
AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/min,
major enantiomer: tR = 18.4 min; minor enantiomer: tR = 20.4 min.
1H NMR (400 MHz, CDCl3): d 1.22 (t, J = 7.1 Hz, 3H), 1.26 (d,
J = 7.1 Hz, 3H), 1.38 (d, J = 6.9 Hz, 3H), 2.00–2.12 (m, 2H), 3.18
(m, 1H), 3.79 (s, 3H), 3.92–4.05 (m, 4H), 6.73–6.77 (m, 2H), 6.82
(d, J = 7.7 Hz, 1H), 7.20–7.24 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 16.3, 16.4, 23.3 (d, J = 9.0 Hz), 33.5, 34.8 (d, J = 2.0 Hz), 55.2,
61.3 (d, J = 6.0 Hz), 61.5 (d, J = 6.0 Hz), 111.5, 112.6, 119.0, 129.5,
148.4 (d, J = 13.0 Hz), 159.7; 31P NMR (162 MHz, CDCl3): d 30.5.
4.2.19. (E)-Diethyl 2-phenylpent-1-enylphosphonate (E)-1r12
Colorless oil, yield: 30%. 1H NMR (400 MHz, CDCl3): d 0.92 (t,
J = 7.4 Hz, 3H), 1.36 (t, J = 7.0 Hz, 6H), 1.39–1.45 (m, 2H), 2.95–
2.99 (m, 2H), 4.09–4.17 (m, 4H), 5.76 (d, J = 17.1 Hz, 1H), 7.34–
7.36 (m, 3H), 7.39–7.40 (m, 2H); 13C NMR (100 MHz, CDCl3): d
13.9, 16.4, 16.5, 22.0, 34.4 (d, J = 7.0 Hz), 61.4, 61.5, 114.1 (d,
J = 189.0 Hz), 126.5, 128.5, 128.9, 141.2 (d, J = 24.0 Hz), 163.6 (d,
J = 9.0 Hz); 31P NMR (162 MHz, CDCl3): d 18.3.
4.3.4. Diethyl 2-(4-methoxyphenyl)propylphosphonate 2d
94% ee. ½a 2D5
¼ þ21:7 (c 0.84, CHCl3). HPLC conditions: chiralcel
ꢂ
AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/min,
major enantiomer: tR = 18.1 min; minor enantiomer: tR = 19.9 min.
1H NMR (400 MHz, CDCl3): d 1.21 (t, J = 7.1 Hz, 3H), 1.25 (t,
J = 7.1 Hz, 3H), 1.36 (d, J = 6.9 Hz, 3H), 1.99–2.09 (m, 2H), 3.15–
3.20 (m, 1H), 3.78 (s, 3H), 3.90–4.04 (m, 4H), 6.84 (d, J = 8.6 Hz,
2H), 7.15 (d, J = 8.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 16.3,
16.4, 23.7 (d, J = 10.0 Hz), 33.8, 35.1, 55.2, 61.2 (d, J = 7.0 Hz), 61.4
(d, J = 6.0 Hz), 113.8, 127.6, 138.8 (d, J = 12.0 Hz), 158.1; 31P NMR
(162 MHz, CDCl3): d 30.7. HRMS calcd for C14H23O4P: 286.1334,
found 286.1338.
4.2.20. (E)-Diethyl (2,3-dihydronaphthalen-4(1H)-ylid-ene)
methylphosphonate (E)-1s
Colorless oil, yield: 22%. 1H NMR (400 MHz, CDCl3): d 1.16 (t,
J = 7.4 Hz, 6H), 1.93–1.99 (m, 2H), 2.58–2.61 (m, 2H), 2.83–2.86
(m, 2H), 3.92–3.99 (m, 4H), 5.56 (d, J = 14.4 Hz, 1H), 7.10–7.12
(m, 1H), 7.18–7.22 (m, 1H), 7.26–7.29 (m, 1H), 8.04–8.06 (m,
1H); 13C NMR (100 MHz, CDCl3): d 16.0, 16.1, 23.6, 29.3, 36.8 (d,
J = 22.0 Hz), 61.4, 61.5, 110.2 (d, J = 188.0 Hz), 125.3, 128.1, 129.6
(d, J = 15.0 Hz), 133.5 (d, J = 6.0 Hz), 138.9, 158.6; 31P NMR
(162 MHz, CDCl3): d 17.9.
4.3.5. Diethyl 2-(2-methylphenyl)propylphosphonate 2e
4.3. General procedure for the asymmetric hydrogenation of
86% ee. ½a 2D5
¼ þ11:9 (c 0.76, CHCl3). HPLC conditions: chiralcel
ꢂ
a,b-unsaturated phosphonates
AD-H, 40 °C, n-hexane /i-propanol = 97/3, flow rate = 1.0 mL/min,
major enantiomer: tR = 9.2 min; minor enantiomer: tR = 10.5 min.
1H NMR (400 MHz, CDCl3): d 1.21 (t, J = 7.1 Hz, 3H), 1.24 (t,
J = 7.1 Hz, 3H), 1.35 (d, J = 6.9 Hz, 3H), 2.00–2.06 (m, 2H), 2.38 (s,
3H), 3.17–3.20 (m, 1H), 3.90–4.01 (m, 4H), 7.08–7.11 (m, 2H),
7.17–7.18 (m, 2H); 13C NMR (100 MHz, CDCl3): d 16.3, 16.4, 19.4,
22.9 (d, J = 9.0 Hz), 29.5 (d, J = 29.0 Hz), 33.7 (d, J = 137.0 Hz), 61.2
(d, J = 7.0 Hz), 61.3 (d, J = 7.0 Hz), 125.1, 126.1, 126.3, 130.4,
135.0, 144.8 (d, J = 11.0 Hz); 31P NMR (162 MHz, CDCl3): d 30.8.
HRMS calcd for C14H23O3P: 270.1385, found 270.1380.
In nitrogen-filled glovebox, [Rh(COD)2]BF4 (1.0 mg,
a
0.0025 mmol) and (Sc,Sp)-WalPhos (1.8 mg, 0.0028 mmol) were
dissolved in degassed CH2Cl2 (1 mL) in a 5 mL vial. After stirring
at room temperature for 15 min, a solution of
a,b-unsaturated
phosphonate 1 (0.25 mmol, S/C 100:1) in 1 mL of degassed CH2Cl2
was added. The resulting mixture was transferred to an autoclave,
which was then charged with H2 (10 atm). The hydrogenation was
performed at room temperature for 24 h. After carefully releasing
the hydrogen gas, the reaction was purified through a plug of silica
gel (eluting with a mixture of hexanes/EtOAc) to afford 2. The
enantiomeric excess was determined by HPLC on a chiral column.
4.3.6. Diethyl 2-(3-methylphenyl)propylphosphonate 2f
94% ee. ½a 2D5
¼ þ18:5 (c 0.92, CHCl3). HPLC conditions: chiralcel
ꢂ
AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/min,
major enantiomer: tR = 10.1 min; minor enantiomer: tR = 11.0 min.
1H NMR (400 MHz, CDCl3): d 1.21 (t, J = 7.1 Hz, 3H), 1.25 (t,
J = 7.1 Hz, 3H), 1.39 (d, J = 6.9 Hz, 3H), 2.00–2.11 (m, 2H), 2.33 (s,
3H), 3.17–3.20 (m, 1H), 3.90–4.05 (m, 4H), 7.00–7.03 (m, 3H),
7.17–7.20 (m, 1H); 13C NMR (100 MHz, CDCl3): d 16.3, 16.4, 21.4,
23.5 (d, J = 6.0 Hz), 34.3 (d, J = 137.0 Hz), 34.6, 61.2 (d, J = 6.0 Hz),
61.4 (d, J = 6.0 Hz), 123.6, 127.1, 127.4, 128.4, 138.0, 146.7 (d,
J = 12.0 Hz); 31P NMR (162 MHz, CDCl3): d 30.7. HRMS calcd for
C14H23O3P: 270.1385, found 270.1384.
4.3.1. Diethyl 2-phenylpropylphosphonate 2a5
93.0% ee. ½a 2D5
¼ þ17:85 (c 0.82, CHCl3). HPLC conditions: chi-
ꢂ
ralcel AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/
min, major enantiomer: tR = 11.1 min; minor enantiomer:
tR = 12.2 min. 1H NMR (400 MHz, CDCl3): d 1.20 (t, J = 7.1 Hz, 3H),
1.24 (t, J = 7.1 Hz, 3H), 1.39 (d, J = 7.0 Hz, 3H), 1.98–2.13 (m, 2H),
3.19–3.24 (m, 1H), 3.88–4.02 (m, 4H), 7.17–7.24 (m, 3H), 7.26–
7.31 (m, 2H); 13C NMR (100 MHz, CDCl3): d 16.3, 16.3, 23.5 (d,
J = 10.0 Hz), 34.6 (d, J = 13.0 Hz), 34.8 (d, J = 23.0 Hz), 61.2 (d,
J = 6.0 Hz), 61.4 (d, J = 6.0 Hz), 126.4, 126.6, 128.5, 146.6 (d,
J = 12.0 Hz); 31P NMR (162 MHz, CDCl3): d 30.5.
4.3.7. Diethyl 2-(4-methylphenyl)propylphosphonate 2g5
94% ee. ½a 2D5
¼ þ22:15 (c 0.74, CHCl3). HPLC conditions: chir-
ꢂ
4.3.2. Diethyl 2-(2-methoxyphenyl)propylphosphonate 2b
alpak AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/
min, major enantiomer: tR = 11.9 min; minor enantiomer:
tR = 13.3 min. 1H NMR (400 MHz, CDCl3): d 1.21 (t, J = 7.1 Hz, 3H),
87% ee. ½a 2D5
¼ þ5:7 (c 0.88, CHCl3). HPLC conditions: chiralcel
ꢂ
AD-H, 40 °C, n-hexane/i-propanol = 98/2, flow rate = 1.0 mL/min,

Z. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 508–514
513
1.25 (t, J = 7.1 Hz, 3H), 1.37 (d, J = 7.0 Hz, 3H), 2.00–2.10 (m, 2H),
2.31 (s, 3H), 3.19 (m, 1H), 3.91–4.04 (m, 4H), 7.11–7.13 (m, 4H);
13C NMR (100 MHz, CDCl3): d 16.3, 16.4, 20.9, 23.5 (d, J = 9.0 Hz),
34.2 (d, J = 3.0 Hz), 35.4 (d, J = 137.0 Hz), 61.2 (d, J = 6.0 Hz), 61.4
(d, J = 6.0 Hz), 126.5, 129.1, 135.8, 143.7 (d, J = 12.0 Hz); 31P NMR
(162 MHz, CDCl3): d 30.7.
3.21 (m, 1H), 3.91–4.05 (m, 4H), 7.10–7.13 (m, 2H), 7.41–7.43
(m, 2H); 13C NMR (100 MHz, CDCl3): d 16.4, 23.5 (d, J = 10.0 Hz),
34.2 (d, J = 138.0 Hz), 34.3, 61.4 (d, J = 6.0 Hz), 61.5 (d, J = 7.0 Hz),
120.0, 128.5, 131.5, 145.6 (d, J = 11.0 Hz); 31P NMR (162 MHz,
CDCl3): d 30.0. HRMS calcd for C13H20BrO3P: 334.0333, found
334.0344.
4.3.8. Diethyl 2-(3-(trifluoromethyl)phenyl)propylphos-phonate
2h
4.3.13. Diethyl 2-(naphthalen-2-yl)propylphosphonate 2m5
91% ee. ½a 2D5
¼ þ24:2 (c 1.04, CHCl3). HPLC conditions: chiralcel
ꢂ
92% ee. ½a 2D5
ꢂ
¼ þ18:7 (c 0.92, CHCl3). HPLC conditions: chiralcel
AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/min,
major enantiomer: tR = 17.6 min; minor enantiomer: tR = 23.0 min.
1H NMR (400 MHz, CDCl3): d 1.14 (t, J = 7.1 Hz, 3H), 1.22 (t,
J = 7.1 Hz, 3H), 1.47 (d, J = 6.9 Hz, 3H), 2.10–2.22 (m, 2H), 3.40
(m, 1H), 3.87–4.04 (m, 4H), 7.35–7.46 (m, 3H), 7.66 (s, 1H), 7.77–
AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/min,
major enantiomer: tR = 12.9 min; minor enantiomer: tR = 14.1 min.
1H NMR (400 MHz, CDCl3): d 1.19 (t, J = 7.1 Hz, 3H), 1.23 (t,
J = 7.1 Hz, 3H), 1.41 (d, J = 7.0 Hz, 3H), 2.04–2.13 (m, 2H), 3.27–
3.32 (m, 1H), 3.90–4.02 (m, 4H), 7.42–7.48 (m, 4H); 13C NMR
(100 MHz, CDCl3): d 16.2 (d, J = 4.0 Hz), 16.2 (d, J = 5.0 Hz), 23.5
(d, J = 10.0 Hz), 34.1 (d, J = 139.0 Hz), 34.7, 61.4 (d, J = 5.0 Hz),
61.4 (d, J = 6.0 Hz), 123.3 (d, J = 3.0 Hz), 123.5 (d, J = 3.0 Hz),
129.0, 130.3, 147.4 (d, J = 11.0 Hz); 31P NMR (162 MHz, CDCl3): d
29.6. HRMS calcd for C14H20F3O3P: 324.1102, found 324.1110.
7.79 (m, 3H); 13C NMR (100 MHz, CDCl3):
d 16.3, 16.3 (d,
J = 6.0 Hz), 23.4 (d, J = 9.0 Hz), 34.2 (d, J = 137.0 Hz), 34.8, 61.3 (d,
J = 6.0 Hz), 61.5 (d, J = 6.0 Hz), 124.9, 125.2, 125.4, 126.0, 127.6,
127.6, 128.2, 132.3, 133.6, 144.10 (d, J = 11.0 Hz); 31P NMR
(162 MHz, CDCl3): d 30.5.
4.3.14. Diethyl 2-(thiophen-2-yl)propylphosphonate 2n
4.3.9. Diethyl 2-(4-(trifluoromethyl)phenyl)propylphos-phonate
2i5
98% ee. ½a 2D5
¼ þ18:6 (c 0.60, CHCl3). HPLC conditions: chiralcel
ꢂ
AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/min,
major enantiomer: tR = 12.0 min; minor enantiomer: tR = 13.1 min.
1H NMR (400 MHz, CDCl3): d 1.26 (t, J = 7.1 Hz, 3H), 1.28 (t,
J = 7.1 Hz, 3H), 1.48 (d, J = 6.9 Hz, 3H), 2.02–2.10 (m, 1H), 2.15–
2.21 (m, 1H), 3.54 (m, 1H), 3.98–4.08 (m, 4H), 6.85–6.86 (m, 1H),
6.89–6.91 (m, 1H), 7.12–7.13 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 16.4, 16.4, 24.2 (d, J = 7.0 Hz), 30.4 (d, J = 2.0 Hz), 35.7 (d,
J = 138.0 Hz), 61.4 (d, J = 7.0 Hz), 61.5 (d, J = 6.0 Hz), 122.9, 123.0,
126.5, 150.9 (d, J = 15.0 Hz); 31P NMR (162 MHz, CDCl3): d 29.5.
HRMS calcd for C11H19O3PS: 262.0793, found 262.0793.
93% ee. ½a 2D5
¼ þ18:2 (c 0.92, CHCl3). HPLC conditions: chiralcel
ꢂ
AD-H, 40 °C, n-hexane/i-propanol = 98/2, flow rate = 1.0 mL/min,
major enantiomer: tR = 17.3 min; minor enantiomer: tR = 20.0 min.
1H NMR (400 MHz, CDCl3): d 1.19 (t, J = 7.1 Hz, 3H), 1.24 (t,
J = 7.1 Hz, 3H), 1.40 (d, J = 7.0 Hz, 3H), 2.04–2.12 (m, 2H), 3.27–
3.31 (m, 1H), 3.90–4.04 (m, 4H), 7.36 (d, J = 8.1 Hz, 2H), 7.56 (d,
J = 8.1 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 16.2 (d, J = 6.0 Hz),
16.3 (d, J = 5.0 Hz), 23.4 (d, J = 10.0 Hz), 34.0 (d, J = 139.0 Hz),
34.7, 61.4 (d, J = 7.0 Hz), 61.4 (d, J = 6.0 Hz), 122.8, 125.4 (d,
J = 3.0 Hz), 127.2, 128.7 (q, J = 32.0 Hz), 150.5 (d, J = 10.0 Hz); 31P
NMR (162 MHz, CDCl3): d 29.7.
4.3.15. Diethyl 2-methyl-4-phenylbutylphosphonate 2o11
96% ee. ½a 2D5
¼ þ12:3 (c 0.86, CHCl3). HPLC conditions: chiralcel
ꢂ
4.3.10. Diethyl 2-(4-fluorophenyl)propylphosphonate 2j
OJ-H, 40 °C, n-hexane/i-propanol = 98/2, flow rate = 1.0 mL/min,
major enantiomer: tR = 12.4 min; minor enantiomer: tR = 10.9 min.
1H NMR (400 MHz, CDCl3): d 1.11 (d, J = 6.6 Hz, 3H), 1.30 (t,
J = 7.0 Hz, 6H), 1.56–1.67 (m, 2H), 1.76–1.79 (m, 2H), 1.83–1.84
(m, 1H), 2.58–2.66 (m, 2H), 4.02–4.09 (m, 4H), 7.14–7.18 (m,
3H), 7.24–7.28 (m, 2H); 13C NMR (100 MHz, CDCl3): d 16.4, 16.5,
20.8 (d, J = 7.0 Hz), 28.0 (d, J = 4.0 Hz), 32.8 (d, J = 138.0 Hz), 33.1,
40.0 (d, J = 4.0 Hz), 61.3 (d, J = 6.0 Hz), 61.3 (d, J = 5.0 Hz), 125.7,
128.3, 142.2; 31P NMR (162 MHz, CDCl3): d 32.0.
94% ee. ½a 2D5
¼ þ17:3 (c 0.78, CHCl3). HPLC conditions: chiralcel
ꢂ
AD-H, 40 °C, n-hexane/i-propanol = 98/2, flow rate = 1.0 mL/min,
major enantiomer: tR = 19.7 min; minor enantiomer: tR = 21.1 min.
1H NMR (400 MHz, CDCl3): d 1.20 (t, J = 7.1 Hz, 3H), 1.25 (t,
J = 7.1 Hz, 3H), 1.36 (d, J = 7.0 Hz, 3H), 2.00–2.09 (m, 2H), 3.21–
3.24 (m, 1H), 3.90–4.03 (m, 4H), 6.96–7.01 (m, 2H), 7.18–7.22
(m, 2H); 13C NMR (100 MHz, CDCl3): d 16.3, 16.3, 23.7, 33.8, 35.1,
61.2, 61.4, 115.2, 128.2, 132.0, 142.3, 160.2, 162.6; 31P NMR
(162 MHz, CDCl3): d 30.2. HRMS calcd for C13H20FO3P: 274.1134,
found 274.1133.
4.3.16. Diethyl 2-phenylbutylphosphonate 2p
93% ee. ½a 2D5
¼ þ10:0 (c 1.14, CHCl3). HPLC conditions: chiralcel
ꢂ
4.3.11. Diethyl 2-(4-chlorophenyl)propylphosphonate 2k
OJ-H, 40 °C, n-hexane/i-propanol = 98/2, flow rate = 1.0 mL/min,
major enantiomer: tR = 9.3 min; minor enantiomer: tR = 7.8 min.
1H NMR (400 MHz, CDCl3): d 0.75 (t, J = 7.2 Hz, 3H), 1.14 (t,
J = 7.2 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H), 1.60–1.66 (m, 1H), 1.82–
1.87 (m, 1H), 2.06–2.14 (m, 2H), 2.91–2.92 (m, 1H), 3.76–3.96
(m, 4H), 7.17–7.21 (m, 3H), 7.27–7.30 (m, 2H); 13C NMR
(100 MHz, CDCl3): d 11.8, 16.2, 16.3, 30.8 (d, J = 8.0 Hz), 32.8 (d,
J = 139.0 Hz), 41.9 (d, J = 2.0 Hz), 61.2 (d, J = 7.0 Hz), 61.4 (d,
J = 7.0 Hz), 126.4, 127.6, 128.3, 144.4 (d, J = 8.0 Hz); 31P NMR
(162 MHz, CDCl3): d 30.9. HRMS calcd for C14H23O3P: 270.1385,
found 270.1387.
94% ee. ½a 2D5
¼ þ23:4 (c 0.92, CHCl3). HPLC conditions: chiralcel
ꢂ
AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/min,
major enantiomer: tR = 12.5 min; minor enantiomer: tR = 13.6 min.
1H NMR (400 MHz, CDCl3): d 1.21 (t, J = 7.1 Hz, 3H), 1.25 (t,
J = 7.1 Hz, 3H), 1.36 (d, J = 6.9 Hz, 3H), 1.99–2.08 (m, 2H), 3.18–
3.22 (m, 1H), 3.90–4.05 (m, 4H), 7.16–7.18 (m, 2H), 7.28–7.31
(m, 2H); 13C NMR (100 MHz, CDCl3): d 16.3, 16.4, 23.5 (d,
J = 10.0 Hz), 34.2 (d, J = 138.0 Hz), 34.2, 61.3 (d, J = 6.0 Hz), 61.4
(d, J = 7.0 Hz), 128.1, 128.5, 132.0, 145.0 (d, J = 11.0 Hz); 31P NMR
(162 MHz, CDCl3): d 30.0. HRMS calcd for C13H20ClO3P: 290.0839,
found 290.0826.
4.3.17. Diethyl 2-(4-methoxyphenyl)butylphosphonate 2q
4.3.12. Diethyl 2-(4-bromophenyl)propylphosphonate 2l
94% ee. ½a 2D5
¼ þ10:45 (c 1.18, CHCl3). HPLC conditions: chiral-
ꢂ
95% ee. ½a 2D5
ꢂ
¼ þ22:7 (c 1.06, CHCl3). HPLC conditions: chiralcel
cel OJ-H, 40 °C, n-hexane/i-propanol = 98/2, flow rate = 1.0 mL/
min, major enantiomer: tR = 11.6 min; minor enantiomer:
tR = 10.4 min. 1H NMR (400 MHz, CDCl3): d 0.75 (t, J = 7.2 Hz, 3H),
1.16 (t, J = 7.2 Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H), 1.58–1.60 (m, 1H),
1.81–1.85 (m, 1H), 2.02–2.11 (m, 2H), 2.91–2.92 (m, 1H), 3.78 (s,
AD-H, 40 °C, n-hexane/i-propanol = 97/3, flow rate = 1.0 mL/min,
major enantiomer: tR = 14.0 min; minor enantiomer: tR = 15.6 min.
1H NMR (400 MHz, CDCl3): d 1.21 (t, J = 7.1 Hz, 3H), 1.25 (t,
J = 7.1 Hz, 3H), 1.36 (d, J = 6.9 Hz, 3H), 1.99–2.07 (m, 2H), 3.16–

514
Z. Duan et al. / Tetrahedron: Asymmetry 23 (2012) 508–514
3H), 3.80–3.98 (m, 4H), 6.82–6.85 (m, 2H), 7.09–7.12 (m, 2H); 13C
NMR (100 MHz, CDCl3): d 11.8, 16.2, 16.3, 30.8 (d, J = 13.0 Hz), 32.9
(d, J = 138.0 Hz), 41.0 (d, J = 3.0 Hz), 55.2, 61.1 (d, J = 7.0 Hz), 61.3
(d, J = 6.0 Hz), 113.7, 128.5, 136.4 (d, J = 8.0 Hz), 158.1; 31P NMR
(162 MHz, CDCl3): d 30.9. HRMS calcd for C15H25O4P: 300.1490,
found 300.1491.
References
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4.3.18. Diethyl 2-phenylpentylphosphonate 2r
93% ee. ½a 2D5
¼ þ7:9 (c 1.22, CHCl3). HPLC conditions: chiralcel
ꢂ
OJ-H, 40 °C, n-hexane/i-propanol = 98/2, flow rate = 1.0 mL/min,
major enantiomer: tR = 7.4 min; minor enantiomer: tR = 6.6 min.
1H NMR (400 MHz, CDCl3): d 0.84 (t, J = 7.2 Hz, 3H), 1.09–1.18
(m, 2H), 1.14 (t, J = 7.2 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H), 1.58–1.63
(m, 1H), 1.74–1.79 (m, 1H), 2.06–2.13 (m, 2H), 3.00–3.04 (m, 1H),
3.74–3.97 (m, 4H), 7.17–7.20 (m, 3H), 7.26–7.30 (m, 2H); 13C
NMR (100 MHz, CDCl3):
d 13.9, 16.2, 16.3, 20.4, 33.1 (d,
J = 139.0 Hz), 39.9 (d, J = 3.0 Hz), 40.1 (d, J = 13.0 Hz), 61.1 (d,
J = 6.0 Hz), 61.3 (d, J = 6.0 Hz), 126.4, 127.5, 128.2 (d, J = 16.0 Hz),
144.6 (d, J = 8.0 Hz); 31P NMR (162 MHz, CDCl3): d 30.9. HRMS
calcd for C15H25O3P: 284.1541, found 284.1536.
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4.3.19. Diethyl (1,2,3,4-tetrahydronaphthalen-1-yl)
methylphosphonate 2s
93% ee. ½a 2D5
¼ ꢁ3:5 (c 0.94, CHCl3). HPLC conditions: chiralcel
ꢂ
OD-H, 40 °C, n-hexane/i-propanol = 95/5, flow rate = 1.0 mL/min,
major enantiomer: tR = 6.8 min; minor enantiomer: tR = 8.8 min.
1H NMR (400 MHz, CDCl3): d 1.34 (t, J = 7.2 Hz, 3H), 1.77–1.84
(m, 2H), 1.98–2.01 (m, 2H), 2.04–2.16 (m, 2H), 2.73–2.78 (m,
2H), 3.29 (m, 1H), 4.12–4.14 (m, 4H), 7.04–7.08 (m, 1H), 7.10–
7.15 (m, 2H), 7.18–7.20 (m, 1H); 13C NMR (100 MHz, CDCl3): d
16.4, 16.5, 19.2, 28.5, 29.4, 32.5, 33.4 (d, J = 136.0 Hz), 61.4 (d,
J = 6.0 Hz), 61.6 (d, J = 6.0 Hz), 126.0 (d, J = 9.0 Hz), 128.6, 129.3,
136.9, 140.3 (d, J = 17.0 Hz); 31P NMR (162 MHz, CDCl3): d 31.2.
HRMS calcd for C15H23O3P: 282.1385, found 282.1382.
Acknowledgements
Financial support from the Key Project of Chinese Ministry of
Education (211111), Project of Hubei Provincial Department of
Education (Q2011902), and Fund of Hubei University for National-
ities (MY2010T003, MY2010B009) is gratefully acknowledged.
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