Application of asymmetric aminohydroxylation to heteroaromatic acrylates

Article abstract of DOI:10.1016/S0957-4166(00)00308-6

Furyl and thienyl acrylates could be aminohydroxylated with high selectivity, but pyrrolyl acrylates resist aminohydroxylation under the present reaction conditions. The corresponding aminohydroxylation products, the 3-amino-2-hydroxy-3-(2-furyl)propionat

Full text of DOI:10.1016/S0957-4166(00)00308-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 3439–3447
Application of asymmetric aminohydroxylation to
heteroaromatic acrylates
Hongxing Zhang,c Peng Xiab and Weishan Zhoua,*
aShanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
bDepartment of Organic Chemistry, Pharmacy School, Shanghai Medical University, Shanghai 200032, China
cDepartment of Chemistry, Shanghai Medical University, Shanghai 200032, China
Received 14 July 2000; accepted 8 August 2000
Abstract
Furyl and thienyl acrylates could be aminohydroxylated with high selectivity, but pyrrolyl acrylates
resist aminohydroxylation under the present reaction conditions. The corresponding aminohydroxylation
products, the 3-amino-2-hydroxy-3-(2-furyl)propionate derivative and the 3-amino-2-hydroxy-3-(2-
thienyl)propionate derivative, could be easily converted to the b-hydroxy-a-amino acids. The dihydropy-
ridone obtained from the 3-amino-2-hydroxy-3-(2-furyl)propionate derivative is a chiral building block for
synthesis of polyhydroxy indolizidine alkaloids. © 2000 Published by Elsevier Science Ltd.
1. Introduction
Optically active a-furfuryl amine derivatives can be applied directly to the synthesis of natural
and unnatural a-amino acids by oxidation of a furan ring to a carboxyl group (1“2) by
2
ozonolysis1 or oxidation with RuCl3/NaIO4 (Scheme 1). The most important application of
these compounds is that they can be converted into the dihydropyridone derivatives (1“3) via
the aza-Achmatowicz reaction3 or Lefebvre oxidation4 (Scheme 1). Therefore, a-furfuryl amine
Scheme 1.
* Corresponding author. Tel: 86-21-64163300; fax: 86-21-64166128; e-mail: zhws@pub.sioc.ac.cn
0957-4166/00/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0957-4166(00)00308-6

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derivatives 1 are useful chiral building blocks for the synthesis of a great number of nitrogen
containing natural products.5
In our laboratory, we have developed some new methods for preparing chiral a-furfuryl
amine derivatives, such as the kinetic resolution of racemic a-furfuryl amine derivatives,6
diastereoselective addition of organometallic reagents to the imines7 and reduction of
azidoalcohol8c and their applications to the asymmetric synthesis of natural and unnatural
amino acids,9 piperidine alkaloids,10 polyhydroxy indolizidine alkaloids11 and 1-deoxyazasug-
ars.8 The Sharpless asymmetric aminohydroxylation (AA) of alkenes12 has proved to be one of
the most reliable methods for the asymmetric functionalization of alkenes, which allows the
simultaneous introduction of a protected amino and a hydroxyl group onto an alkene. First, we
employed a-furyl ethylene derivatives as substrates using chloramine-T or the sodium salt of
N-chloroethylcarbamate as nitrogen sources, but only moderate regio- and stereoselectivity were
achieved.13 At about the same time, O’Doherty et al.14 also applied this reaction to the same
substrate but using the sodium salt of N-chlorobenzylcarbamate as the nitrogen source and got
similar results. Herein we report our further application of this reaction to the furyl acrylates as
well as the thienyl and pyrrolyl acrylates using N-bromoacetamide or sodium salt of N-
chlorobenzylcarbamate as the nitrogen source, respectively.
2. Results and discussion
The acrylates 4a–4f were readily synthesized by Wittig reactions from the corresponding
aldehydes and ethyl phosphoraylidene acetate. We first carried out the aminohydroxylation of
4a–4f using (DHQ)2PHAL as the chiral ligand, and the lithium salt of N-bromoacetamide as the
nitrogen source.15 The aminohydroxylation of 4a proceeded sluggishly at 0°C in low yields, but
proceeded smoothly in 54% yield in 70% conversion at 25°C with moderate regioselectivity but
low enantioselectivity (entry 1, Table 1). However, when increasing the electron density in the
furan moiety by the donor methyl substituent (entry 2, Table 1), the AA reaction occurred
smoothly at 0°C, but the regioselectivity and enantioselectivity were very low. In contrast to the
furyl acrylates (entries 1 and 2, Table 1), the thienyl acrylate 4c proved to be an excellent
substrate for the AA both in terms of reactivity and selectivity (entry 3, Table 1). A single
recrystallization of the product 5c was enough to remove the minor regioisomer. The pyrrolyl
acryates 4c–4e proved to be problematic substrates (entries 4–6, Table 1). No AA reactions
occurred even on raising the reaction temperature and changing the nitrogen protecting groups.
Owing to the failure to obtain the desired AA product of the furyl acrylate using N-bromo-
acetamide as the nitrogen source, we turned our attention to another nitrogen source, the
sodium salt of N-chlorobenzylcarbamate16 (Scheme 2, Table 2). The furyl acrylate 4a could be
aminohydroxylated both with high regioselectivity and high enantioselectivity (entry 1, Table 2).
Moreover, the regioisomer could be separated by flash chromatography. Unlike a recent
report,17 we obtained the AA products of 3-[2-(5-methylfuryl)] acrylate 4b with excellent
regioselectivity and enantioselectivity in 68% yield (entry 2, Table 2). The thienyl acrylate was
also aminohydroxylated smoothly with high regioselectivity and enantioselectivity in the case of
the sodium salt of N-chlorobenzylcarbamate (entry 3, Table 2). The pyrrolyl acrylates were not
good substrates using the sodium salt of N-chlorobenzylcarbamate as the nitrogen source (entry
4–6, Table 2). When t-butyl methyl ether was added in the reaction mixture to increase the
solubility of substrates, the dihydroxylated product was mainly obtained instead of the AA
product for 4e16a in 55% yield.

H. Zhang et al. / Tetrahedron: Asymmetry 11 (2000) 3439–3447
3441
Table 1
AA reactions using AcNLiBr as the nitrogen source
Scheme 2.
This aminohydroxylation of the furyl acrylate for the preparation of a-furfuryl amine
derivatives probably has advantage over our previous methods. Since the AA product bears the
hydroxyl group, which is vicinal to the amino group, it is a useful building block for preparation
of b-hydroxy-a-aminoacids and dihydropyridone 12. The latter possesses an a-hydroxy carboxy-
late in the C2-position of the pyridone ring, so it is particularly favorable for the synthesis of
polyhydroxy indolizidine alkaloids such as castanospermine 13.
After the hydroxyl group was protected with acetic anhydride, 3-(benzyloxycarbonylamino)-2-
hydroxy-3-(2-furyl)propionate 7a and 3-(benzyloxycarbonylamino)-2-hydroxy-3-(2-thienyl) prop-
ionate 7c, were subjected to ozonolysis at 0°C using CH2Cl2/MeOH (10:1) as a solvent to lead
to the b-hydroxy-a-aminoacid derivative 10 in 63 and 66% yields, respectively (Scheme 3).

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H. Zhang et al. / Tetrahedron: Asymmetry 11 (2000) 3439–3447
Table 2
AA reactions using BnOCONNaCl as the nitrogen source
The synthesis towards the polyhydroxy indolizidine alkaloids starting from 7a was demon-
strated (Scheme 4). After the hydroxyl group was protected by MOMCl, 11 was treated with
m-CPBA8c to afford the desired dihydropyridone 12, which is a preferable intermediate of
polyhydroxy indolizidine alkaloids such as castanospermine 13, which possess potent bioactivity
as inhibitors of glucosidase and glycoprotein processing18 and also exhibit interesting anticancer,
antiviral and immunoregulatory activities.19 We are currently advancing this intermediate
towards the synthesis of these alkaloids.
Scheme 3.
Scheme 4.

H. Zhang et al. / Tetrahedron: Asymmetry 11 (2000) 3439–3447
3443
In conclusion, the furyl and thienyl acrylates could be aminohydroxylated with high selectivity,
but the pyrrolyl acrylates resist AA in the present reaction conditions. The 3-amino-2-hydroxy-3-
(2-furyl)propionate derivative 7a and 3-amino-2-hydroxy-3-(2-thienyl)propionate derivative 7c
could be easily converted to b-hydroxy-a-aminoacid. Dihydropyridone 12 obtained from
3-amino-2-hydroxy-3-(2-furyl)propionate derivative 7a is an excellent building block for the
synthesis of polyhydroxy indolizidine alkaloids, such as castanospermine 13 which is our ultimate
goal.
3. Experimental
3.1. General
Melting points were determined with a Bu¨chi 535 melting point apparatus and were
uncorrected. Reactions were monitored by using thin layer chromatography (TLC). The silica gel
used in flash chromatography was silica gel H (10–40 mm) which was produced by Qingdao
1
Chemical Plant, China. IR spectra were measured on a Schimadzu IR 400 spectrometer. H
NMR spectra were recorded on a Bruker AM-300 (300 MHz) with CDCl3 as solvent and values
were reported in ppm using TMS or residual CHCl3 as internal standard. MS spectra were
conducted on a Finnigan 4021 GC–MS instrument and JMS-01U spectrometer. The optical
rotations, were measured at 20°C on a Perkin–Elmer 241 MC automatic polarimeter in a 1 dm
cell and recorded in units of 10−1 deg cm2 g−1. Element analysis was performed by the analytical
department of this institute.
3.2. General procedure for the N-bromoacetamide-based AA
All N-bromoacetamide-based AA reactions (entries 1–6 in Table 1) were performed as
described here for 5c (entry 3, Table 1).
3.2.1. Synthesis of 5c
In 3 ml of an aqueous solution of LiOH·H2O (42.8 mg, 1.02 mmol), K2[OsO2(OH)4] (14.7 mg,
0.04 mmol, 4 mol%) was dissolved with stirring. After addition of t-BuOH (6 mL),
(DHQ)2PHAL (39 mg, 0.05 mmol, 5 mol%) was added and the mixture was stirred for 10 min
to give a clear solution. Water (6 mL) was added subsequently, and the mixture was immersed
in an ice bath to 0°C. After addition of 4c (182 mg, 1 mmol), N-bromoacetamide (151.8 mg, 1.1
mmol) was added in one portion (which resulted in an immediate color change to green) and the
mixture was vigorously stirred at the same temperature. The reaction was monitored by TLC.
After 12 h the reaction mixture was treated with Na2SO3 (0.5 g). After stirring at room
temperature for 30 min, ethyl acetate (10 mL) was added. The organic layer was separated, and
the water layer was extracted with ethyl acetate (3×10 mL). The combined organic extracts were
washed with brine (5 mL), and dried over anhydrous Na2SO4. After evaporation of the solvent
under reduced pressure, the crude product was purified by flash chromatography on silica gel
(petroleum ether:ethyl acetate 1:1) and recrystallized from petroleum ether:ethyl acetate to give
208 mg (81% yield, 87% ee) of 5c. [h]2D0=+43 (c=1, EtOH); m.p. 112–114°C; H NMR l: 1.32
1
(t, 3H, J=7.00 Hz, Et), 1.99 (s, 3H, Ac), 4.30 (q, 2H, J=7.10 Hz, Et), 4.54 (m, 1H, NH), 5.84
(d, 1H, J=9.26 Hz), 6.20 (d, 1H, J=9.04 Hz), 6.98 (m, 1H), 7.11 (m, 1H), 7.24 (m, 1H); IR: 3326,

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H. Zhang et al. / Tetrahedron: Asymmetry 11 (2000) 3439–3447
3207, 1718 cm−1; MS m/z: 258 (M++1), 239 (M+–H2O), 199 (M+−NHAc), 154; anal. calcd for
C11H15NO4S: C, 51.35; H, 5.88; N, 5.44. Found: C, 51.28; H, 5.84; N, 5.35.
3.2.2. Synthesis of 5a
The preparation of 5a was carried out according to general procedure by using 0.166 g of 4a
(1 mmol). The reaction mixture was stirred at 25°C for 20 h. The crude product was purified by
column chromatography (petroleum ether:ethyl acetate 1:1) to give the starting material 4a
1
(0.050 g, 70% conversion) and an oil 5a (0.091 g, 54% yield). H NMR l: 1.32 (t, 3H, J=7.00
Hz, Et), 2.01 (s, 3H, Ac), 4.27 (q, 2H, J=7.00 Hz, Et), 4.59 (d, 1H, J=1.14 Hz, NH), 5.64 (dd,
1H, J=1.92, 9.26 Hz), 6.25 (d, 1H, J=9.25 Hz), 6.30 (m, 1H), 6.34 (m, 1H), 7.38 (d, 1H,
J=1.10 Hz); IR: 3326, 3210, 1743, 1718 cm−1; MS m/z: 242 (M++1), 224 (M++1-H2O), 183
(M+−NHAc), 138; anal. calcd for C11H15NO5: C, 54.77; H, 6.27; N, 5.81. Found: C, 54.31; H,
6.56; N, 5.42.
3.2.3. Synthesis of the mixture of 5b and 6b
The preparation of the mixture of 5b and 6b was carried out according to general procedure
by using 0.180 g of 4b (1 mmol). The reaction mixture was stirred at 0°C for 12 h. The crude
product was purified by column chromatography (petroleum ether:ethyl acetate 2:3) to give a
1
white solid, a mixture of 5b and 6b (ratio 1:1.5) (0.132 g, 52% yield). H NMR for 5b: l: 1.30
(t, 3H, J=7.00 Hz, Et), 2.00 (s, 3H, Ac), 2.27 (s, 3H, Me), 4.27 (q, 2H, J=7.00 Hz, Et), 4.56
1
(br s, 1H, NH), 5.57 (m, 1H), 5.90 (m, 1H), 6.17 (m, 1H), 6.30 (d, 1H, J=8.30 Hz); H NMR
for 6b: l: 1.30 (t, 3H, J=7.00 Hz, Et), 2.04 (s, 3H, Ac), 2.27 (s, 3H, Me), 4.27 (q, 2H, J=7.00
Hz, Et), 4.97 (dd, 1H, J=3.53, 8.55 Hz), 5.13 (br s, 1H, NH), 5.90 (m, 1H), 6.17 (m, 2H); IR:
3356, 3219, 1741cm−1; MS m/z: 256 (M++1), 238 (M++1-H2O), 197 (M+−NHAc), 152, 111; anal.
calcd for C12H17NO5: C, 56.46; H, 6.71; N, 5.49. Found: C, 56.18; H, 6.78; N, 5.37.
3.3. General procedure for the benzyl carbamate-based AA
All benzyl carbamate-based AA reactions (entries 1–6 in Table 2) were performed as described
here for 7a (entry 1, Table 2).
3.3.1. Synthesis of 7a
A 50 mL round-bottom flask was charged with benzyl carbamate (0.182 g, 1.20 mmol) and
t-BuOH (4 mL). To this stirred solution were added a freshly prepared aqueous solution of
NaOH (0.046 g, 1.15 mmol in 7.5 mL water) and tert-butyl hypochlorite (0.125 g, 1.15 mmol).
After 10 min, a solution of (DHQ)2PHAL (40 mg, 0.05 mmol, 5 mol%) in t-BuOH (3.5 mL) was
added. Ethyl furylacrylate 4a (0.166 g, 1 mmol, dissolved in 5 mL of t-BuOH) was then added,
followed by addition of K2OsO2(OH)4 (15 mg, 0.08 mmol, 4 mol%). The mixture was stirred at
25°C for 3.5 h, and a saturated aqueous sodium sulfite solution (10 mL) was added to quench
the reaction. The two phases were separated, and the aqueous phase was extracted with ethyl
acetate (3×10 mL). The combined organic phase was washed with water and brine, dried over
anhydrous Na2SO4, and concentrated under the reduced pressure. The residue was purified by
flash chromatography on silica gel (petroleum ether:ethyl acetate 8:1–3:1) to afford the starting
material 4a (0.068 g, 59% conversion), the desired product 7a (0.122 g, 62% yield, 87% ee) as an
oil and the regioisomer 8a (0.016 g, 8% yield) as an oil. For 7a: [h]2D0=+23.3 (c=0.9, EtOH); H
1
NMR l: 1.26 (t, 3H, J=7.03 Hz, Et), 4.26 (q, 2H, J=7.02 Hz, Et), 4.59 (d, 1H, J=1.75 Hz,

H. Zhang et al. / Tetrahedron: Asymmetry 11 (2000) 3439–3447
3445
NH), 5.11 (br s, 2H, CH2Ph), 5.37 (d, 1H, J=9.06 Hz), 5.51 (m, 1H), 6.30 (d, 1H, J=3.02 Hz),
6.33 (m, 1H), 7.35 (m, 5H, Ph), 7.38 (d, 1H, J=1.07 Hz); IR: 3369, 1731 cm−1; MS m/z: 334
(M++1), 316 (M++1-H2O), 183 (M+−NHCbz), 230; anal. calcd for C17H19NO6: C, 61.25; H, 5.75;
N, 4.20. Found: C, 61.20; H, 5.56; N, 4.19. For 8a: [h]2D0=+2.5 (c=0.8, EtOH); 1H NMR l: 1.27
(t, 3H, J=7.13 Hz, Et), 4.24 (q, 2H, J=7.03 Hz, Et), 4.75 (d, 1H, J=6.25 Hz), 5.10 (br s, 2H,
CH2Ph), 5.21 (d, 1H, J=2.95 Hz, NH), 5.61 (d, 1H, J=8.40 Hz), 6.32 (m, 2H), 7.27–7.34 (m,
6H); IR: 3412, 1728 cm−1; MS m/z: 334 (M++1), 316 (M++1-H2O), 288, (M+−EtO), 97; anal.
calcd for C17H19NO6: C, 61.25; H, 5.75; N, 4.20. Found: C, 61.21; H, 5.81; N, 4.17.
3.3.2. Synthesis of 7b
The preparation of 7b was carried out according to general procedure by using 0.180 g of 4b
(1 mmol). The reaction mixture was stirred at 25°C for 3 h. The crude product was purified by
column chromatography (petroleum ether:ethyl acetate:dichloromethane 5:5:1) to give the
starting material 4b (0.040 g, 78% conversion) and an oil 7b (0.184 g, 68% yield, 99% ee).
1
[h]2D0=+18.8 (c=0.9, EtOH); H NMR l: 1.27 (t, 3H, J=7.03 Hz, Et), 2.26 (s, 3H, Me), 4.25
(q, 2H, J=7.00 Hz, Et), 4.56 (br s, 1H, NH), 5.10 (br s, 2H, CH2Ph), 5.29 (d, 1H, J=9.00 Hz),
5.50 (d, 1H, J=9.72 Hz), 5.90 (m, 1H), 6.16 (d, 1H, J=2.93 Hz), 7.36 (m, 5H, Ph); IR: 3377,
1732 cm−1; MS m/z: 348 (M++1), 330 (M++1-H2O), 244; anal. calcd for C18H21NO6: C, 62.24; H,
6.09; N, 4.03. Found: C, 61.93; H, 6.16; N, 3.96.
3.3.3. Synthesis of 7c
The preparation of 7c was carried out according to general procedure by using 0.182 g of 4c
(1 mmol). The reaction mixture was stirred at 25°C for 3 h. The crude product was purified by
column chromatography (petroleum ether:ethyl acetate 5:1) and recrystallized from petroleum
ether:ethyl acetate to give a colorless solid 7c (0.246 g, 71% yield, 99% ee). [h]2D0=+32 (c=0.75,
1
EtOH); m.p. 89–90°C; H NMR l: 1.27 (t, 3H, J=7.04 Hz, Et), 4.25 (q, 2H, J=7.00 Hz, Et),
4.51 (br s, 1H, NH), 5.10 (m, 2H, CH2Ph), 5.57 (m, 2H), 6.97 (dd, 1H, J=3.70, 5.00 Hz), 7.09
(d, 1H, J=2.88 Hz), 7.24 (m, 1H), 7.33 (m, 5H, Ph); IR: 3356, 3318, 1741, 1676 cm−1; MS m/z:
350 (M++1), 332 (M++1-H2O), 246, 199 (M+−NHCbz); anal. calcd for C17H19NO5S: C, 58.44; H,
5.48; N, 4.01. Found: C, 58.32; H, 5.31; N, 3.93.
3.4. Synthesis of 9a
To a solution of compound 7a (0.105 g, 0.315 mmol) in CH2Cl2 (3 ml) were added
triethylamine (0.088 ml, 0.63 mmol) and DMAP (77 mg, 0.63 mmol) at 0°C. After being stirred
for 0.5 h, acetic anhydride (0.06 mL, 0.63 mmol) was added at the same temperature. The
mixture was then stirred at 0°C for an additional 2 h. Water (5 ml) was added and the aqueous
layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried
over Na2SO4, evaporated under reduced pressure to afford a crude oil which was purified by
flash column chromatography on silica gel (petroleum ether:ethyl acetate 6:1) to afford an oil 9a
(0.101 g, 85% yield). [h]2D0=+8.7 (c=0.4, EtOH); H NMR l: 1.26 (t, 3H, J=7.14 Hz, Et), 2.10
1
(s, 3H, Ac), 4.20 (q, 2H, J=7.18 Hz, Et), 5.12 (br s, 2H, CH2Ph), 5.46 (d, 1H, J=2.28 Hz), 5.54
(m, 2H), 6.23 (d, 1H, J=3.23 Hz), 6.32 (dd, 1H, J=1.86, 3.28 Hz) 7.35 (m, 6H); IR: 3345, 1741,
1726 cm−1; MS m/z: 376 (M++1), 316 (M+−OAc), 269 (M++1-OBn), 230, 225 (M+−NHCbz);
anal. calcd for C19H21NO7: C, 60.79; H, 5.64; N, 3.73. Found: C, 60.79; H, 5.87; N, 3.89.

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H. Zhang et al. / Tetrahedron: Asymmetry 11 (2000) 3439–3447
3.5. Synthesis of 9c
To a solution of compound 7c (0.141g, 0.404 mmol) in CH2Cl2 (3 ml) were added triethyl-
amine (0.118 mL, 0.85 mmol) and DMAP (0.103 g, 0.85 mmol) at 0°C. After being stirred
for 0.5 h, acetic anhydride (0.08 mL, 0.85 mmol) was added at the same temperature. The
mixture was then stirred at 0°C for an additional 2 h. Water (5 ml) was added and the
aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with
brine, dried over Na2SO4, evaporated under reduced pressure to afford a crude oil, which
was purified by flash chromatography on silica gel (petroleum ether:ethyl acetate 5:1) to
afford an oil 9c (0.154 g, 97% yield). [h]2D0=+10.7, (c=1.5, EtOH); H NMR l: 1.26 (t, 3H,
1
J=7.02 Hz, Et), 2.17 (s, 3H, Ac), 4.20 (q, 2H, J=7.00 Hz, Et), 5.10 (m, 2H, CH2Ph), 5.36
(d, 1H, J=1.77 Hz, NH), 5.60 (d, 1H, J=9.42 Hz), 5.74 (d, 1H, J=9.96 Hz), 6.96 (m, 1H),
7.03 (m, 1H) 7.25 (m, 1H), 7.35 (m, 5H, Ph); IR: 3346, 1747, 1720 cm−1; MS m/z: 392
(M++1), 332 (M+−OAc), 285 (M++1-OBn), 246; anal. calcd for C19H21NO6S: C, 58.30; H,
5.41; N, 3.58. Found: C, 58.17; H, 5.42; N, 3.28.
3.6. Synthesis of 10
To a solution of 9a (72 mg, 0.20 mmol) or 9c (78 mg, 0.20 mmol) in CH2Cl2:MeOH (10:1)
(11 mL) was passed ozone at 0°C for approximately 15 min until a light blue color
appeared. The reaction mixture was bubbled with N2 for 5 min at 0°C to remove the excess
ozone, and then Me2S was added (1 mL). After stirring at rt for 1 h, the reaction mixture
was concentrated to give a crude oil, which was purified by flash chromatography on silica
gel to afford 10 as an oil (50 mg, 74% for 9a), (48 mg, 68% for 9c); [h]2D0=−10.8 (c=1.3,
1
EtOH); H NMR l: 1.26 (t, 3H, J=7.20 Hz, Et), 2.11 (s, 3H, Ac), 4.15 (q, 2H, J=7.19 Hz,
Et), 5.12 (m, 3H), 5.61 (m, 2H), 7.33 (m, 5H, Ph); IR: 3367, 1752 cm−1; MS m/z: 353 (M+),
310 (M+−Ac), 246 (M+−OBn), 204 (M++1-NHCbz); anal. calcd for C16H19NO8·3/4H2O: C,
52.43; H, 5.63; N, 3.82. Found: C, 52.43; H, 5.97; N 3.32.
3.7. Synthesis of 11
To a solution of 7a (0.200 g, 0.6 mmol) in CH2Cl2 (0.7 mL) was added DMAP (7 mg,
0.057 mmol), iPr2NEt (0.63 mL, 3.6 mmol) and MOMCl (0.18 mL, 2.4 mmol) at rt. After
stirring at rt for 10 h, 1 mL water was added and the mixture was stirred for 10 min. The
reaction mixture was extracted with 50 mL ethyl acetate. The organic layer was washed with
brine, dried over Na2SO4, evaporated under reduced pressure to afford a crude oil, which
was purified by flash chromatography on silica gel (petroleum ether:ethyl acetate 6:1) to
afford an oil 11 (0.187 g, 82.6% yield). [h]2D0=+45.5 (c=0.85, EtOH); H NMR l: 1.26 (t,
1
3H, J=7.00 Hz, Et), 3.10 (s, 3H, OMe), 4.21 (q, 2H, J=7.00 Hz, Et), 4.51 (d, 1H, J=6.96
Hz, OCHaHbO), 4.64 (d, 1H, J=1.68 Hz, NH), 4.69 (d, 1H, J=6.81 Hz, OCHaHbO), 5.11
(br s, 2H, CH2Ph), 5.43 (d, 1H, J=9.78 Hz), 5.63 (d, 1H, J=9.57 Hz), 6.25 (d, 1H, J=3.18
Hz), 6.33 (dd, 1H, J=1.64, 3.16 Hz), 7.35 (m, 6H); IR: 3333, 1749, 1730 cm−1; MS m/z: 378
(M++1), 362 (M+−CH3), 316 (M+−OCH2OCH3), 230; anal. calcd for C19H23NO7: C, 60.47; H,
6.14; N, 3.71. Found: C, 60.61; H, 6.15; N, 3.67.

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3447
3.8. Synthesis of 12
To a solution of 11 (0.120 g, 0.32 mmol) in 10 ml of dichloromethane was added m-CPBA
(0.066 g, 0.38 mmol). After being stirred for 8 h at rt, the solvent was evaporated under reduced
pressure to give the crude product which was purified by flash chromatography on silica gel
(petroleum ether:ethyl acetate 3:1) to afford an oil 12 (0.098 g, 78% yield). [h]2D0=+70.3 (c=1.8,
1
EtOH); H NMR l: 1.28 (t, 3H, J=7.14 Hz, Et), 3.23 (s, 3H, OMe), 4.02–4.18 (m, 2H), 4.62
(m, 3H), 5.20 (m, 3H), 6.01 (d, 1H, J=4.38 Hz, 6%-H), 6.21 (d, 1H, J=10.37 Hz, 4%-H), 6.96 (dd,
1H, J=4.84, 10.27 Hz, 5%-H), 7.37 (m, 5H, Ph); IR: 3364, 1750, 1713, 1689 cm−1; MS m/z: 376
(M++1-H2O), 332 (M+−OCH2OCH3); anal. calcd for C19H23NO8: C, 58.01; H, 5.89; N, 3.56.
Found: C, 58.01; H, 5.98; N, 3.53.
Acknowledgements
This project (29732061) was supported by the National Natural Science Foundation of China.
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