Bismuth(III) chloride-catalyzed three-component coupling: Synthesis of α-amino phosphonates

Article abstract of DOI:10.1080/00397910500212692

A simple and efficient method has been developed for the one-pot synthesis of α-amino phosphonates from the reaction of a carbonyl compound, amine, and dialkyl phosphite. The highly catalytic nature of bismuth(III) chloride and the fact that it is relatively nontoxic, low cost, easy to handle, and insensitive to small amounts of air and moisture make this method especially attractive for large-scale synthesis. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1080/00397910500212692

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Bismuth(III) Chloride–Catalyzed
Three‐Component Coupling:
Synthesis of α‐Amino
Phosphonates
a
a
Zhuang‐Ping Zhan & Jun‐Ping Li
a
Department of Chemistry and the Key Laboratory
for Chemical Biology of Fujian Province, College
of Chemistry and Chemical Engineering , Xiamen
University , Xiamen, China
Published online: 18 Aug 2006.
To cite this article: Zhuang‐Ping Zhan & Jun‐Ping Li (2005) Bismuth(III)
Chloride–Catalyzed Three‐Component Coupling: Synthesis of α‐Amino Phosphonates,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 35:19, 2501-2508
To link to this article: http://dx.doi.org/10.1080/00397910500212692
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Synthetic Communications , 35: 2501–2508, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500212692
Bismuth(III) Chloride–Catalyzed Three-
Component Coupling: Synthesis of a-Amino
Phosphonates
Zhuang-Ping Zhan and Jun-Ping Li
Department of Chemistry and the Key Laboratory for Chemical Biology
of Fujian Province, College of Chemistry and Chemical Engineering,
Xiamen University, Xiamen, China
Abstract: A simple and efficient method has been developed for the one-pot synthesis
of a-amino phosphonates from the reaction of a carbonyl compound, amine, and
dialkyl phosphite. The highly catalytic nature of bismuth(III) chloride and the fact
that it is relatively nontoxic, low cost, easy to handle, and insensitive to small
amounts of air and moisture make this method especially attractive for large-scale
synthesis.
Keywords: Amine, a-amino phosphonate, bismuth trichloride, carbonyl compound,
dialkyl phosphite
a-Amino phosphonates are key compounds as analogues of a-amino acids in
[
medicinal chemistry and pharmaceutical sciences. The potential of a-amino
1]
[
2]
[3]
phosphonates as haptens of catalytic antibodies, enzyme inhibitors, and
[
4]
antibiotic and pharmacologic agents has been established. Thus, how to effi-
ciently synthesize a-amino phosphonates has been explored. Of the methods
available, the nucleophilic addition of phosphites to imines is most
[5]
convenient. These reactions are usually promoted by a base or an acid.
Received in Japan May 8, 2005
Address correspondence to Zhuang-Ping Zhan, Department of Chemistry and the
Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, China. Fax: þ86-592-
2
185780; E-mail: zpzhan@xmu.edu.cn
2
501

2502
Z.-P. Zhan and J.-P. Li
.
Lewis acids such as SnCl , SnCl , BF OEt , ZnCl , and MgBr have been
2
4
3
2
2
2
[
6]
found to be effective. However, these reactions cannot be carried out in a
one-pot operation with carbonyl compound, amine, and phosphite, because
amine and water produced during imine formation can decompose or deactivate
[
7]
these Lewis acids. Recently, it has been reported that using lanthanide triflate,
[
8]
[9]
samarium diiodide, scandium tris(dodecyl sulfate), indium(III) chloride,
[10]
[
2
11]
and TaCl -SiO
5
as catalysts, one-pot reactions can proceed smoothly.
However, some of these catalysts are either expensive or somewhat difficult
to prepare.
Of late, bismuth(III) compounds have received attention because of their
low toxicity, low cost, and relative insensitivity to air and small amounts of
moisture. As Lewis acids, bismuth(III) compounds have been used in many
[
12]
chemical transformations.
Herein, we report that bismuth(III) chloride is
a highly efficient catalyst for the one-pot synthesis of a-amino phosphonates
from a carbonyl compound, amine, and dialkyl phosphite.
First, the reaction of benzaldehyde with aniline and diethyl phosphite was
carried out using 10 mol% BiCl as a catalyst. Several solvents and reaction
3
conditions were investigated. The results are summarized in Table 1.
The reaction in acetonitrile worked best at reflux. Compared with the
result obtained at room temperature, the yield of a-amino phosphonates
increased prominently at reflux condition (entries 1, 3). Effects of solvents
on the yields of a-amino phosphonates were tested at reflux conditions
(entries 3, 5, 6). Acetonitrile (92%) was a much better solvent in terms of
yields than THF (51%) and dichloromethane (27%). Although MgSO or
4
˚
A mol. sieves as additives were needed when using Yb(OTf) or SmI to
4
catalyze this conversion,
3
2
[
7a,8]
in our method, such additives can be dispensed
with. The reaction proceeded smoothly both with and without molecular
sieves, giving the product in similar yields (entries 1–4).
A typical experimental procedure is as follows: a mixture of a carbonyl
compound (3 mmol), an amine (3 mmol), and a dialkyl phosphite (3 mmol)
Table 1. Effect of reaction conditions on the BiCl -catalyzed reaction of benzal-
3
dehyde, aniline, and diethyl phosphite
Reaction
temp.
Time
(h)
Isolated
yield (%)
Entry
Solvent
Additive
—
4 A mol. sieves
1
2
3
4
5
6
CH CN
3
rt
6
6
6
6
6
6
23
26
92
91
27
51
˚
CH
CH
CH
3
3
3
CN
CN
CN
rt
Reflux
Reflux
Reflux
Reflux
—
4 A mol. sieves
˚
CH Cl
2
—
—
2
THF

Synthesis of a-Amino Phosphonates
2503
was added to a solution of BiCl (10 mol%) in acetonitrile (15 mL) and
3
the mixture was stirred at reflux for the period of time required to complete
the reaction (TLC). Unlike indium(III) chloride, where inert ambience is
required, the use of an inert atmosphere is not required for our reactions. A
wide range of structurally varied carbonyl compounds were used as substrates
and converted to the corresponding a-amino phosphonates in good to
excellent yields. The results are reported in Table 2.
.
Considering that when using TaCl5 SiO as a catalyst, aliphatic amines
2
gave uncharacterizable products, and when carbonyl compounds were ketones
many catalysts such as lanthanide triflate, samarium diiodide, and scandium
tris(dodecyl sulfate) proved to be less effective, BiCl performed highly
3
efficient catalytic activity for three-component coupling reactions. Not only
benzaldehydes but also electron-rich aromatic aldehydes, electron-deficient
aromatic aldehydes, and aliphatic aldehydes react with aromatic as well as
Table 2. Synthesis of a-amino phosphonates from aldehydes, ketones, and amines
catalyzed by BiCl
3
Time
(h)
1
2
R
3
R
4
a
Entry
R
R
4/%
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
—
—
Ph
Et
6
5
4a/92
4b/92
4c/95
4d/95
4e/93
4f/90
4g/85
4h/82
4i/83
4j/90
4k/91
4l/82
Ph
Ph
Ph
Ph
Ph
Me
i-Pr
Et
6
p-MeO-Ph
o-MeO-Ph
2,4-Dichloro-C
p-MeO-Ph
o-HO-Ph
8
Et
Et
10
12
13
8
6
H
4
b
n-Pr
Ph
Et
Et
p-NO
Cyclohexyl
2
-Ph
Ph
Ph
Me
Et
7
1
1
1
1
1
1
1
1
1
6
Ph
Ph
PhCH
PhCH2
2
Et
14
12
9
Me
Et
PhCH 55 CH (trans)
Cyclohexanone
Cyclohexanone
PhCH
PhCH
n-Pr
2
2
4m/81
4n/80
Et
Et
15
7
b
4o/87
c
CH
Cyclopentanone
CH3
3
CH
—
3
PhCH
n-Pr
2
Et
Et
9
4p/86
b
15
28
4q/83
Isobutyl
PhCH2
Et
4r/70
a
b
c
Isolated yields after column chromatography.
The reaction was carried out at 458C.
The reaction was carried out at 538C.

2504
Z.-P. Zhan and J.-P. Li
aliphatic amines to give the a-amino phosphonates in high yields. This
procedure is equally effective for conversion of ketone to the respective
dialkyl phosphonates. Several sensitive functionalities such as NO , OMe,
2
OH, Cl, and the C-C double bond are unaffected in the reaction. The advan-
tages of this method are operational simplicity, no requirement for an inert
atmosphere for the reaction, and no requirement of an additive. The highly
catalytic nature of bismuth(III) chloride and the fact that it is relatively
nontoxic, low cost, easy to handle, and insensitive to small amounts of air
and moisture make this procedure especially attractive for large-scale
synthesis.
EXPERIMENTAL
Infrared spectra were measured with a Nicolet Avatar 360 FT-IR spectro-
1
meter. H NMR and C NMR spectra were recorded in CDCl on a Varian
13
3
Unity þ500 spectrometer with tetramethylsilane (TMS) as an internal
standard. Chemical shifts are expressed in d (ppm) units downfield from
TMS. Mass spectra were recorded by Bruker Dalton Esquire 3000 Plus and
Finnigan Mat-LCQ (ESI direct injection). Elemental analysis were
performed using a Vario RL analyzer.
General Procedure for the Preparation of 4a–4r
A mixture of carbonyl compound (3 mmol), amine (3 mmol), dialkyl phosphite
(3 mmol), and bismuth trichloride (10 mol%) in acetonitrile (15 mL) was
stirred under reflux for 5–28 h. The acetonitrile was removed at reduced
pressure. Water was added to the residue and the mixture extracted with
EtOAc. The combined organic layers were dried over anhydrous Na SO , con-
2
4
centrated in vacuo, and purified by chromatography on silica gel to afford pure
a-amino phosphonates.
1
The H NMR, MS, and IR spectral data of those known compounds are
1
13
given. The H NMR, C NMR, MS, and IR spectra data and CHN analysis
result of the new compounds are also given.
2
1
Product of 4a: IR (film): 3294, 1603, 1498, 1234, 1024, 969 cm
H NMR (500 MHz, CDCl ): d 7.48–7.08 (10H, m), 4.76 (1H, d,
;
1
2
3
JPH ¼ 24.0 Hz), 4.18–4.05 (2H, m), 3.98–3.89 (1H, m), 3.72–3.63 (1H,
m), 1.28 (3H, t, J ¼ 7.0 Hz), 1.11 (3H, t, J ¼ 7.0 Hz); ESI-MS: m/z
þ
þ
(
%) ¼ 320 (68) [M þ H ], 342 (100) [M þ Na ].
2
1
Product of 4b: IR (film): 3415, 1602, 1499, 1238, 1056, 1030 cm ;
H NMR (500 MHz, CDCl ): d 7.42–6.52 (10H, m), 4.78–4.70 (2H, m), 3.70
1
3
3
3
13
(
3H, d, J ¼ 11.0 Hz), 3.41 (3H, d, J ¼ 11.0 Hz); C NMR (125 MHz,
PH
PH
CDCl ): d 145.98, 145.86, 135.43, 129.03, 128.57, 127.91, 127.66, 127.63,
3
1
18.35, 113.70, 56.06, 54.86, 53.68; ESI-MS: m/z (%) ¼ 292 (39) [M þ Hþ],

Synthesis of a-Amino Phosphonates
2505
þ
3
N, 4.81. Found: C, 61.70; H, 6.57; N, 4.63.
14 (100) [M þ Na ]; Analysis calculated for C H NO P: C, 61.85; H, 6.23;
1
5
18
3
2
1
Product of 4c: IR (film): 3416, 1603, 1499, 1453, 1233, 999 cm
H NMR (500 MHz, CDCl ): d 7.51–6.59 (10H, m), 4.83–4.79 (1H, m),
;
1
3
4
.74–4.66 (2H, m), 4.50–4.43 (1H, m), 1.33 (3H, d, J ¼ 6.0 Hz), 1.28 (3H,
1
3
d, J ¼ 6.0 Hz), 1.23 (3H, d, J ¼ 6.0 Hz), 0.93 (3H, d, J ¼ 6.0 Hz); C
NMR (125 MHz, CDCl ): d 146.54, 146.42, 136.16, 129.08, 128.38, 128.36,
3
1
5
27.97, 127.92, 127.69, 118.15, 113.72, 72.04, 71.98, 71.89, 71.84, 57.00,
þ
5.79, 24.21, 24.16, 23.70, 23.13; ESI-MS: m/z (%) ¼ 370 (100) [M þ Na ];
Analysis calculated for C H NO P: C, 65.69; H, 7.54; N, 4.03. Found:
3
1
9
26
C, 65.62; H, 7.47; N, 4.10.
Product of 4d: IR (film): 3301, 1603, 1510, 1245, 1025, 971 cm ; H NMR
21 1
2
(
500 MHz, CDCl ): d7.40–6.58 (9H, m), 4.72 (1H, d, J ¼ 24.0 Hz), 4.17–4.06
3
PH
(
2H, m), 3.98–3.92 (1H, m), 3.77 (3H, s), 3.73–3.66 (1H, m), 1.28 (3H, t,
þ
J ¼ 7.0 Hz), 1.14 (3H, t, J ¼ 7.0 Hz); ESI-MS: m/z (%) ¼ 350 (66) [M þ H ],
þ
3
72 (100) [M þ Na ].
2
1
Product of 4e: IR (film): 3416, 1603, 1499, 1233, 1056, 971 cm
H NMR (500 MHz, CDCl ): d 7.40–6.50, (9H, m), 5.32 (1H, dd,
;
1
3
J ¼ 16.0 Hz, J ¼ 8.0 Hz), 4.80–4.76, (1H, m), 4.12–4.08 (2H, m), 3.85
1
2
(
3H, s), 3.83–3.78 (1H, m), 3.56–3.52 (1H, m), 1.23 (3H, t, J ¼ 7.0 Hz),
1
3
0
1
1
1
.96 (3H, t, J ¼ 7.0 Hz); C NMR (125 MHz, CDCl ): d 157.22, 157.17,
3
46.26, 146.16, 129.09, 128.97, 128.14, 124.45, 120.99, 120.90, 118.01,
13.48, 113.44, 110.34, 62.99, 62.93, 55.68, 48.52, 47.29, 16.29, 16.06,
þ
þ
5.83, 15.78; ESI-MS: m/z (%) ¼ 350 (100) [M þ H ], 372 (86) [M þ Na ];
Analysis calculated for C H NO P: C, 61.88; H, 6.92; N, 4.01. Found:
1
8
24
3
C, 61.82; H, 7.00; N, 4.00.
Product of 4f: IR (film): 3415, 1603, 1499, 1233, 1056, 1025 cm
2
1
;
1
2
H NMR (500 MHz, CDCl ): d 7.54–6.56 (8H, m), 5.32 (1H, d, J
¼
3
PH
2
4.0 Hz), 4.27–4.20 (2H, m), 4.00–3.93 (1H, m), 3.79–3.71 (1H, m), 1.36
1
3
(3H, t, J ¼ 7.0 Hz), 1.14 (3H, t, J ¼ 7.0 Hz); C NMR (125 MHz, CDCl3):
d 145.41, 145.29, 134.69, 134.63, 134.15, 134.12, 132.89, 129.75, 129.72,
1
5
4
29.26, 129.13, 127.70, 118.69, 113.42, 63.59, 63.54, 63.46, 63.40, 51.80,
þ
0.58, 16.42, 16.37, 16.14, 16.09; ESI-MS: m/z (%) ¼ 388 (90) [M þ H ],
þ
10 (100) [M þ Na ]; Analysis calculated for C H Cl NO P: C, 52.59;
1
7
20
2
3
H, 5.19; N, 3.61. Found: C, 52.74; H, 5.20; N, 3.68.
Product of 4g: IR (film): 3439, 1610, 1512, 1249, 1029, 966 cm
2
1
;
1
H NMR (500 MHz, CDCl ): d 7.21 (2H, d, J ¼ 7.5 Hz), 6.75 (2H, d,
3
J ¼ 7.5 Hz), 4.05–3.96 (2H, m), 3.90–3.85 (2H, m), 3.77–3.73 (1H, m),
3
.71 (3H, s), 2.42–2.28 (2H, m), 1.41–1.33 (2H, m), 1.19 (3H, t,
J ¼ 7.0 Hz), 1.07 (3H, t, J ¼ 7.0 Hz), 0.77 (3H, t, J ¼ 7.0 Hz); ESI-MS:
þ
þ
m/z (%) ¼ 316 (100) [M þ H ], 338 (24) [M þ Na ].
21 1
Product of entry 4h: IR (film): 3407, 1603, 1503, 1458, 1207, 1051,
1
024 cm ; H NMR (500 MHz, CDCl ): d 7.28–6.67 (9H, m), 4.92 (1H,
3
2
d, JPH ¼ 23.0 Hz), 4.19–3.97 (4H, m), 1.28–1.17 (6H, m); ESI-MS:
þ
þ
m/z (%) ¼ 336 (39) [M þ H ], 358 (100) [M þ Na ].

2506
Z.-P. Zhan and J.-P. Li
2
1
Product of 4i: IR (film): 3418, 1632, 1520, 1347, 1206, 1052 cm
;
1
H NMR (500 MHz, CDCl ): d 8.20 (2H, d, J ¼ 8.5 Hz), 7.68 (2H, dd,
3
4
J ¼ 8.5 Hz, J ¼ 2.0 Hz), 7.13–7.09 (2H, m), 6.75–6.71 (1H, m), 6.57–
PH
3
6
3
.55 (2H, m), 5.00–4.91 (1H, m), 3.81 (3H, d, J ¼ 5.3 Hz), 3.63 (3H, d,
PH
13
JPH ¼ 5.3 Hz); C NMR (125 MHz, CDCl ): d 147.43, 145.35, 145.24,
3
1
43.59, 129.15, 128.51, 128.48, 123.67, 118.92, 113.61, 55.80, 54.62,
4.08, 54.03, 53.71, 53.66; ESI-MS: m/z (%) ¼ 337 (41) [M þ H ], 375
þ
5
þ
(
100) [M þ K ]; Analysis calculated for C H N O P: C, 53.57; H, 5.10;
1
5 17 2 5
N, 8.33. Found: C, 53.54; H, 5.17; N, 8.12.
2
1
Product of 4j: IR (film): 3423, 1602, 1499, 1230, 1054, 1026 cm
H NMR (500 MHz, CDCl ): d 7.09–7.05 (2H, m), 6.62–6.65 (3H, m),
;
1
3
4
m), 1.90–1.54 (7H, m); 1.25–1.01 (10H, m); C NMR (125 MHz, CDCl3):
.04–3.96 (3H, m), 3.94–3.86 (1H, m), 3.83–3.77 (1H, m), 3.59–3.51 (1H,
1
3
d 147.65, 147.62, 129.13, 117.62, 113.04, 62.55, 62.50, 61.73, 61.67, 56.49,
5
5.29, 39.77, 39.73, 30.89, 28.19, 26.19, 25.90, 16.37, 16.32, 16.27; ESI-
þ
þ
MS: m/z (%) ¼ 326 (100) [M þ H ], 348 (54) [M þ Na ]; Analysis
calculated for C H NO P: C, 62.75; H, 8.67; N, 4.30. Found: C, 63.15; H,
3
1
7
28
8
.63; N, 4.33.
Product of 4k: IR (film): 3444, 1633, 1494, 1453, 1242, 1027,
2
66 cm ; H NMR (500 MHz, CDCl ): d 7.38–7.16, (10H, m), 4.07–3.85
1 1
9
3
2
(
4H, m), 3.78–3.70 (2H, m), 3.47 (1H, d, J ¼ 13.0 Hz), 2.40 (1H, s),
PH
1
.20 (3H, t, J ¼ 7.0 Hz), 1.05 (3H, t, J ¼ 7.0 Hz). ESI-MS: m/z (%) ¼ 334
þ
(100) [M þ H ].
2
1
Product of 4l: IR (film): 3439, 1633, 1494, 1453, 1241, 1029 cm
H NMR (500 MHz, CDCl ): d 7.46–7.25 (10H, m), 4.07 (1H, d,
;
1
3
2
3
JPH ¼ 20.5 Hz), 3.82 (1H, d, J ¼ 15.0 Hz), 3.75 (3H, d, J ¼ 10.5 Hz),
PH
1
.57–3.53 (4H, m); C NMR (125 MHz, CDCl ): d 139.03, 135.31,
3
3
1
5
3
35.28, 128.49, 128.44, 128.27, 128.21, 127.95, 127.93, 127.04, 59.72,
8.49, 53.66, 53.61, 53.34, 53.29, 51.06, 50.92; ESI-MS: m/z (%) ¼ 306
þ
þ
(
100) [M þ H ], 328 (98) [M þ Na ]; Analysis calculated for C H NO P:
1
6
20
3
C, 62.94; H, 6.60; N, 4.59. Found: C, 63.08; H, 6.97; N, 4.81.
Product of 4m: IR (film): 3424, 1639, 1453, 1277, 1052, 1026,
2
1 1
9
69 cm ; H NMR (500 MHz, CDCl ): d 7.42–7.16 (10H, m), 6.28 (1H,
3
4
dd, J ¼ 16.0 Hz, J ¼ 4.0 Hz), 6.08–6.03 (1H, m), 4.10–3.45 (7H, m),
PH
1
.28 (3H, t, J ¼ 7.0 Hz), 1.18 (3H, t, J ¼ 7.0 Hz); ESI-MS: m/z (%) ¼ 360
þ þ
(100) [M þ H ], 382 (53) [M þ Na ].
Product of 4n: IR (film): 3439, 1633, 1453, 1234, 1061, 1026,
21 1
69 cm ; H NMR (500 MHz, CDCl ): d 7.43–7.23 (5H, m), 4.20–4.14
3
9
4
(
4H, m), 3.92 (2H, d, J ¼ 3.0 Hz), 1.89–1.85 (2H, m); 1.78–1.68 (6H,
PH
m), 1.52–1.49 (2H, m), 1.35 (6H, t, J ¼ 7.0 Hz); ESI-MS: m/z (%) ¼ 326
þ
þ
(
100) [M þ H ], 348 (49) [M þ Na ].
2
1
Product of 4o: IR (film): 3441, 1632, 1444, 1234, 1026, 954 cm
H NMR (500 MHz, CDCl ): d 4.14–4.07 (4H, m), 2.68 (2H, dt,
;
1
3
4
JPH ¼ 2.5 Hz, J ¼ 10.0 Hz), 1.80–1.42 (12H, m), 1.31 (6H, t, J ¼ 7.0 Hz),
1
3
0
.94 (3H, t, J ¼ 7.5 Hz); C NMR (125 MHz, CDCl ): d 60.82, 60.76,
3

Synthesis of a-Amino Phosphonates
2507
5
5.58, 54.45, 43.74, 29.03, 25.01, 23.60, 19.30, 19.21, 15.96, 15.92, 11.16;
þ
þ
ESI-MS: m/z (%) ¼ 278 (100) [M þ H ], 300 (20) [M þ Na ]; Analysis
calculated for C H NO P: C, 56.30; H, 10.18; N, 5.05. Found: C, 56.37;
3
1
3
28
H, 10.31; N, 5.15.
2
1
Product of 4p: IR (film): 3439, 1634, 1454, 1229, 1050, 958 cm
H NMR (500 MHz, CDCl ): d 7.37–7.22 (5H, m), 4.22–4.13 (4H, m),
;
1
3
1
3
.92 (2H, s), 1.39–1.33 (12H, m), C NMR (125 MHz, CDCl ): d 140.98,
3
1
1
3
28.28, 128.10, 127.88, 63.13, 62.04, 54.09, 47.49, 46.98, 23.63, 22.60,
þ
7.06, 16.08; ESI-MS: m/z (%) ¼ 286 (100) [M þ H ]; Analysis calculated
for C H NO P: C, 58.93; H, 8.48; N, 4.91. Found: C, 58.85; H, 8.89; N, 4.49.
1
4
24
3
2
1
Product of 4q: IR (film): 3425, 1633, 1444, 1227, 1026, 955 cm
H NMR (500 MHz, CDCl ): d 4.14–4.07 (4H, m), 2.68 (2H, dt,
;
1
4
3
JPH ¼ 3.0 Hz, J ¼ 10.0 Hz), 1.80–1.58 (10H, m), 1.31 (6H, t, J ¼ 7.0 Hz),
1
3
0
6
1
.94 (3H, t, J ¼ 7.0 Hz), C NMR (125 MHz, CDCl ): d 64.06, 62.90,
3
1.68, 61.62, 45.70, 34.23, 34.17, 24.59, 24.51, 24.22, 16.57, 16.54,
1.70; ESI-MS: m/z (%) ¼ 264 (100) [M þ H ]; Analysis calculated for
þ
C H NO P: C, 54.74; H, 9.95; N, 5.32. Found: C, 54.51; H, 10.20; N, 5.57.
1
2
26
3
2
1
Product of 4r: IR (film): 3423, 1632, 1453, 1224, 1026, 956 cm
H NMR (500 MHz, CDCl ): d 7.40–7.23 (5H, m), 4.22–4.15 (4H, m),
;
1
3
3
.96, 3.91 (AB-system, 2H, J ¼ 12.0 Hz), 2.07–2.01 (1H, m), 1.76–1.71
(
1H, m), 1.63–1.57 (1H, m), 1.39–1.33 (9H, m), 1.04 (3H, d, J ¼ 6.5 Hz),
1
3
1
1
2
.00 (3H, d, J ¼ 6.5 Hz); C NMR (125 MHz, CDCl ): d 141.17, 128.24,
3
28.04, 126.72, 61.95, 61.89, 61.68, 61.62, 57.67, 56.57, 47.70, 42.10,
5.30, 24.97, 22.92, 22.84, 20.74, 16.61; ESI-MS: m/z (%) ¼ 328 (100)
þ
þ
[
C, 62.36; H, 9.24; N, 4.28. Found: C, 62.56; H, 9.34; N, 4.61.
M þ H ], 350 (29) [M þ Na ]; Analysis calculated for C H NO P:
1
7
30
3
ACKNOWLEDGMENT
Financial support was provided by FuJian Provincial Department of Science
and Technology (No. 2003J019).
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