Asymmetric Baylis-Hillman reaction using sugar acrylates - Synthesis of optically active α-methylene-β-hydroxy alkanoates

Article abstract of DOI:10.1016/S0957-4166(01)00128-8

A study on the asymmetric Baylis-Hillman reaction of three chiral acrylates; 1,2:5,6-di-O-iso-propylidine-α-D-glucofuranose-3-acrylate 1, 2,3:5,6-di-O-iso-propylidine-α-D-mannofuranose-1-acrylate 2 and 1,2-O-iso-propylidine-5-O-tert-butyldimethylsilyl-α-D-xylofuranose-3 -acrylate 3, with various aldehydes was conducted, resulting in adducts with moderate diastereoselectivity (5-40% e.e.).

Full text of DOI:10.1016/S0957-4166(01)00128-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 829–837
Asymmetric Baylis–Hillman reaction using sugar
acrylates—synthesis of optically active a-methylene-b-hydroxy
alkanoates†
Palakodety Radha Krishna,* V. Kannan, A. Ilangovan and G. V. M. Sharma
Discovery Laboratory, Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 29 August 2000; accepted 19 February 2001
Abstract—A study on the asymmetric Baylis–Hillman reaction of three chiral acrylates; 1,2:5,6-di-O-iso-propylidine-a-
D-gluco-
furanose-3-acrylate 1, 2,3:5,6-di-O-iso-propylidine-a- -mannofuranose-1-acrylate 2 and 1,2-O-iso-propylidine-5-O-tert-butyl-
D
dimethylsilyl-a-D-xylofuranose-3-acrylate 3, with various aldehydes was conducted, resulting in adducts with moderate
diastereoselectivity (5–40% e.e.). © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Interest in the asymmetric Baylis–Hillman1–3 protocol
for the formation of homochiral a-methylene-b-
hydroxy-ester (b-hydroxyacrylate) building blocks
results from the utility of these compounds in the
synthesis of natural products and has prompted many
researchers to investigate methods for the stereoselec-
tive generation of this functionality. Successful method-
Our interest in utilising monosaccharides as chirons has
resulted in the synthesis of several natural products,
new glyco-substances,12–14 carrier molecules15 and chiral
auxiliaries.16 Herein, we describe the further use of
monosaccharides as chiral auxiliaries in the preparation
of the sugar acrylates 1, 2 and 3 to effect diastereocon-
trol during the Baylis–Hillman reaction with several
aldehydes (Eq. (1)).
ological
approaches
for
the
enantioselective
Baylis–Hillman reaction have been developed by
Leahy4 using Oppolzer’s sultam, Chen5 who utilised a
camphor based chiral auxiliary and independently by
Barrett6 and Hatakeyama7 who reported the use of
chiral amines. Other methods, including the use of
chiral tertiary amine8 and bis-phosphine catalysts,9
Accordingly, acrylates 1, 2 and 3 (Scheme 1) were
prepared from the corresponding acetonides by reaction
with acryloyl chloride in the presence of Et3N at room
temperature in CH2Cl2. Initially, acrylate 1 was sub-
jected to Baylis–Hillman reaction with 2-nitrobenzalde-
hyde 4 in the presence of a variety of bases. When DBU
was used as the base,17 hydrolysis of the acrylate was
observed and no reaction was seen in THF at room
temperature using either Hu¨nig’s base or n-Bu3P.18
However, the reaction with DABCO afforded acrylate
4a in 91% yield.
10
chalcogenides in the presence of TiCl4 and C2-sym-
metric 2,3-disubstituted DABCO bases,11 gave only
poor to moderate results. Hence, investigation of the
asymmetric Baylis–Hillman reaction using either new
auxiliaries or chiral bases remains an interesting
challenge.
(1)
* Corresponding author. E-mail: prkgenius@iict.ap.nic.in
† IICT Communication No. 4608.
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00128-8

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P. Radha Krishna et al. / Tetrahedron: Asymmetry 12 (2001) 829–837
Scheme 1.
Table 1. Asymmetric Baylis–Hillman reaction of aldehydes with sugar acrylates
S. No.
1
Aldehydea
Chiral acrylate
Time
Yieldb (%)
d.e.d (%)
2-Nitro-benzaldehyde 4
1
2
3
1
2
1
2
1
1
1
1
2 days
2 days
6 days
2 days
2 days
20 h
4a, 91
4b, 88
4c, 85
5a, 87
5b, 86
6ac, 67
6bc, 76
7a, 90
8a, 97
9a, 95
10a, 92
40 (R)
40 (R)
40 (R)
40 (R)
40 (R)
0
2
3
4-Nitro-benzaldehyde 5
Isobutyraldehyde 6
20 h
0
4
5
6
7
Benzaldehyde 7
6 days
2 days
4 days
4 days
5 (R)e
0
2,3-Dichlorobenzaldehyde 8
2-Nitro-5-n-propoxybenzaldehyde 9
2-Nitro-5-methoxybenzaldehyde 10
15 (R)
24 (R)
a DABCO (0.2 equiv.), THF, rt.
b Isolated yields of the respective auxiliary bound adducts.
c Acrylate cleavage was also observed.
d As determined by 1H NMR and HPLC analysis (column Chiralcel OD; 1 cm ID and 25 cm length, n-hexane/propan-2-ol=5.66:1, flow rate=1.6
mL/min, UV=225 nm).
e Based on the literature21 [h]D values for the acid 17.

P. Radha Krishna et al. / Tetrahedron: Asymmetry 12 (2001) 829–837
831
Scheme 2.
The reaction of 4 was carried out independently with 2
and 3 in the presence of DABCO (0.2 equivalents) at
room temperature to afford the adducts 4b (reaction
time: 2 days) and 4c (reaction time: 6 days) in 88 and 85%
yields, respectively (Table 1). Since the Baylis–Hillman
reaction of 4 with 1, 2 and 3 occurred with similar
selectivity it was decided to continue further studies with
1 and 2.
the separate proton resonances for each enantiomer
allowed the ratio of isomeric adducts to be found. For
example, in the 1H NMR spectrum of 4a, the H-1 doublet
resonated at l 5.7 for the minor isomer and at l 5.85 for
the major isomer and the H-2 doublet was observed at
l 4.48 for the major isomer, while the H-2 doublet for
the minor isomer resonated at l 4.4. The integral ratio
for 4a was found to be 7:3 (d.e.=40%).
On changing the solvent from THF to DMSO,5 a marked
increase in the rate of the reaction (which reached
completion in 24 h) was seen. When the temperature of
the reaction between 1 with 4 carried out in THF was
lowered to 0°C, the reaction was unworkably slow and
no improvement in the stereoselectivity was seen.
The study of acrylates 1 and 2 was then extended to the
aldehyde 5 to give the adducts 5a and 5b (Table 1),
respectively, in good yields and moderate enantiomeric
purity. However, aldehyde 6 on reaction with 1 and 2
gave adducts 6a and 6b, respectively, in good chemical
yields albeit with no stereochemical induction.
The structure of the adducts and the diastereoselectivity
of the reactions were unambiguously determined from
the 1H NMR spectrum, where the relative integration of
In a further study, aldehydes 7, 8, 9 and 10 were reacted
with acrylate 1 under the same conditions to give adducts
7a (90%), 8a (97%), 9a (95%) and 10a (92%), respectively,
Scheme 3.

832
P. Radha Krishna et al. / Tetrahedron: Asymmetry 12 (2001) 829–837
with moderate stereochemical induction, as seen in Table
1. The ratios of the diastereomers in these adducts were
determined from the relative integrations in the 1H NMR
spectra. To ascertain the absolute configuration of the
major isomer formed, the adduct 5a was subjected to
hydrolysis (Scheme 2) with LiOH in DME at room
temperature to give the acid 11 in 95% yield, which on
reaction with ethanol in the presence of DCC19-DMAP
was converted into its ethyl ester 12 in good yield.
To establish the absolute configuration of adduct 12,
Katsuki–Sharpless asymmetric epoxidation conditions20
were employed to synthesise reference samples of (R)-12
and (S)-12 by kinetic resolution of the racemate with
(+)-DIPT and (−)-DIPT, respectively. Accordingly, the
requisite ( )-12 was prepared in 97% yield from reaction
of 5 and ethyl acrylate in the presence of DABCO
(Scheme 3). Kinetic resolution of ( )-12 with (+)-DIPT
afforded (R)-12 and epoxide 13. Similarly, reaction of
(−)-DIPT with ( )-12 gave (S)-12 and the epoxide 14.
The specific rotation value of 12 was similar to (R)-12,
hence (R) absolute configuration of the product was
assigned. Further, chiral HPLC (Chiralcel OD) was
consistent with the major isomers of Baylis–Hillman
adducts 4a, 4b, 4c, 5a, 5b, 7a, 9a and 10a obtained with
acrylates 1–3 being of (R) absolute configuration.
Figure 1.
from approach of the incoming aldehyde to the enolate
in such a fashion as to minimise steric interactions with
the bulky alkyl group.
Similarly the other adducts 4a, 7a and 9a were subjected
to the same set of reactions to give acids 15, 17, and 18,
respectively, 15 and 18 were converted into esters 16 and
19, respectively, in good yield (Table 2).
Based on the literature evidence,22,23 the following isox-
azoline intermediate (Fig. 1) was envisaged as the possi-
3. Conclusion
ble enolate of sugar acrylate
1
to give the
The present study demonstrates the use of monosaccha-
ride acrylates for the stereoselective Baylis–Hillman reac-
(R)-stereoisomer as the major product. Selectivity results
Table 2. Hydrolysis and esterification of sugar linked Baylis–Hillman adducts

P. Radha Krishna et al. / Tetrahedron: Asymmetry 12 (2001) 829–837
833
tion resulting in the formation of adducts with yields of
(1.6 mL, 11.53 mmol) for 10 h, as reported for 1, gave
2 (1.96 g, 81%) as a syrup. [h]D=+48.6 (c 1.25, CHCl3);
1H NMR (200 MHz, CDCl3): l 6.4 (s, 1H, olefinic),
6.16 (s, 1H, olefinic), 6.08 (s, 1H, olefinic), 5.9 (d, 1H,
J=0.97 Hz, H-1), 4.82 (m, 1H, H-3), 4.7 (d, 1H,
J=5.85 Hz, H-2), 4.35 (m, 1H, H-4), 4.1–3.92 (m, 3H,
H-5, 6, 6%), 1.5 (s, 3H, CH3), 1.42 (s, 3H, CH3), 1.38
(br.s, 6H, 2CH3). Anal. calcd for C15H22O7: C, 57.32;
H, 7.05. Found: C, 57.27; H, 7.10%.
67–97% and d.e. ratios ranging from 7:3 to 3:2, as
1
determined using H NMR and chiral HPLC analysis.
The selectivities were moderate (5–40% d.e.) and are
comparable with the earlier reported protocols. Further
work on designing new sugar derived acrylates for the
asymmetric Baylis–Hillman reaction and the utility of
Baylis–Hillman adducts is currently under investiga-
tion.
4.3. 1,2-O-iso-Propylidine-5-O-tert-butyldimethylsilyl-a-
D
-xylofuranoside-3-acrylate 3
4. Experimental
To a solution of 1,2-O-iso-propylidene-a-D-xylofura-
Solvents were dried over standard drying agents and
1
noside (0.20 g, 1.05 mmol) and imidazole (0.21 g, 3.15
mmol) in dry DMF (2 mL) was added TBDMSCl (0.16
g, 1.05 mmol) and stirred for 8 h. The reaction mixture
was diluted with ether (10 mL) and washed sequentially
with water (10 mL) and brine (10 mL). The organic
layer was dried (Na2SO4), evaporated under reduced
pressure and the residue was purified by column chro-
matography (silica gel, hexane–EtOAc, 3:1) to afford
freshly distilled prior to use. H NMR (200 and 400
MHz) and 13C NMR (50 MHz) spectra were measured
with
a Varian Gemini spectrometer, with tetra-
methylsilane as internal standard for solutions in deu-
teriochloroform. J values are given in Hz. Optical
rotations were measured with a JASCO DIP-370 instru-
ment and [h]D values are in units of 10−1 deg cm2 g−1.
Organic solutions were dried over anhydrous Na2SO4
and concentrated below 40°C in vacuo. HPLC was
performed with Chiralcel OD column (1 cm ID×25 cm
length) using n-hexane/iso-propanol: 5.66:1, flow rate
16 mL/min, UV 225 nm (unless otherwise stated).
Nomenclature used in the experimental section was
assisted by the software ACD/Name Version 1.0, devel-
oped by M/s Advanced Chemistry Development Inc.,
Toronto, Canada.
1,2-O-iso-propylidine-5-O-tert-butyldimethyl-a-D-xylo-
furanoside (0.32 g, 90%) as a syrup. 1H NMR (200
MHz, CDCl3): l 5.89 (d, 1H, J=3.4 Hz, H-1), 4.43 (d,
1H, J=4.3 Hz, H-3), 4.24 (s, 1H, H-2), 4.18–4.10 (m,
3H, H-4, 5, 5%), 1.47 (s, 3H, CH3), 1.29 (s, 3H, CH3),
0.89 (s, 9H, Me3C), 0.11 (s, 6H, 2CH3).
1,2-O-iso-Propylidine-5-O-tert-butyldimethylsilyl-a-D-
xylofuranoside (0.30 g, 0.98 mmol) was treated with
acryloyl chloride (0.09 mL, 1.08 mmol) and triethy-
lamine (0.20 mL, 1.47 mmol) as reported for 1 to afford
the acrylate 3 (0.40 g, 89%) as a syrup. [h]D=−29.4 (c
4.1. 1,2:5,6-Di-O-iso-propylidine-a-D-glucofuranose-3-
acrylate 1
1
0.53, CHCl3); H NMR (200 MHz, CDCl3): l 6.33 (s,
To a stirred solution of 1,2:5,6-di-O-iso-propylidine-a-
-glucofuranoside (2.0 g, 7.69 mmol) and triethylamine
1H, olefinic), 6.06 (s, 1H, olefinic), 5.85–5.8 (m, 2H,
olefinic, H-1), 5.38 (d, 1H, J=3.72 Hz, H-3), 4.5 (d,
1H, J=4.18 Hz, H-2), 4.22 (m, 1H, H-4), 3.9–3.75 (m,
2H, H-5, 5%), 1.5 (s, 3H, CH3), 1.3 (s, 3H, CH3),
1.12–0.98 (br. s, 9H, Me3C), 0.11 (s, 6H, 2CH3). Anal.
calcd for C17H30O6Si: C, 56.96; H, 8.43. Found: C,
56.87; H, 8.09%.
D
(1.6 mL, 11.53 mmol) in CH2Cl2 (10 mL) acryloyl
chloride (0.68 mL, 8.46 mmol) was added dropwise at
0°C and stirred at room temperature for 10 h. The
reaction mixture was treated with water (25 mL) and
extracted into CH2Cl2 (3×50 mL). The combined
organic layers were washed with water (2×100 mL),
dried (Na2SO4) and evaporated under reduced pressure.
The residue was purified by column chromatography
(silica gel, hexane–EtOAc, 8.5:1.5) to afford the auxil-
iary 1 (2.06 g, 85%) as a white solid. Mp 67–69°C.
The Baylis–Hillman reaction of sugar acrylates with
aldehydes (general procedure)
1
[h]D=−37.9 (c 1, CHCl3); H NMR (CDCl3): l 6.53 (s,
To a solution of acrylate (1 mmol) in dry THF (2 mL)
was added DABCO (0.20 mmol), aldehyde (1.2 mmol)
and the mixture was stirred at room temperature for
2–6 days. The solvent was removed from the mixture
under reduced pressure and the residue purified by
column chromatography (silica gel, hexane–EtOAc) to
afford product in yields of 67–95%.
1H, olefinic), 6.43 (s, 1H, olefinic), 6.18 (s, 1H, olefinic),
5.97 (d, 1H, J=2.04 Hz, H-1), 5.32 (br.s, 1H, H-3), 4.52
(d, 1H, J=3.67 Hz, H-2), 4.22 (m, 2H, H-4, 5), 4.1–4.0
(m, 2H, H-6, 6%), 1.55 (s, 3H, CH3), 1.43 (s, 3H, CH3),
1.3 (br. s, 6H, 2CH3); 13C NMR (50 MHz, CDCl3): l
164.6, 131.7, 127.8, 112.3, 109.3, 105.1, 83.4, 79.8, 76.3,
72.5, 67.1, 26.7, 26.5, 26.2, 25.2. Anal. calcd for
C15H22O7: C, 57.32; H, 7.05. Found: C, 57.20; H,
7.15%.
4.4. 5-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
dimethyl-(3aR,6S,6aR)-perhydrofuro [2,3-d][1,3]-dioxol-
6-yl 2-hydroxy(2-nitrophenyl)methylacrylate 4a
4.2. 2,3:5,6-Di-O-iso-propylidine-a-D-mannofuranose-1-
acrylate 2
To a solution of 1 (0.20 g, 0.64 mmol) in THF (2 mL),
4 (0.12 g, 0.76 mmol) and DABCO (0.014 g, 0.13
mmol) were added and the mixture was allowed to stir
at room temperature for 2 days. Solvent was removed
to give the residue, which on purification by column
Reaction of 2,3:5,6-di-O-iso-propylidine-a-D-manno-
furanoside (2.0 g, 7.69 mmol) and acryloyl chloride
(0.68 mL, 8.46 mmol) in the presence of triethylamine

834
P. Radha Krishna et al. / Tetrahedron: Asymmetry 12 (2001) 829–837
chromatography (silica gel, hexane:EtOAc, 8:2) afforded
4a (0.27 g, 91%) as a syrup. [h]D=−20.9 (c 1.65, CHCl3);
1H NMR (200 MHz, CDCl3): l 8.05–7.95 (m, 1H, Ar-H),
7.85–7.65 (m, 2H, Ar-H), 7.56–7.45 (m, 1H, Ar-H), 6.38
(s, 1H, olefinic), 6.25–6.13 (m, 1H, olefinic), 5.85 (d, 0.7H,
J=3.81 Hz, H-1), 5.7 (d, 0.3H, J=3.81 Hz, H-1), 5.55
(s, 1H, benzylic), 5.3 (d, 0.7H, J=3.33 Hz, H-3), 5.22 (d,
0.3H, J=3.33 Hz, H-3), 4.48 (d, 0.7H, J=3.81 Hz, H-2),
4.4 (d, 0.3H, J=3.81 Hz, H-2), 4.2–3.95 (m, 4H, H-4, 5,
6, 6%), 3.4–3.25 (bs, 1H, -OH), 1.56–1.2 (br.s, 12H, 4CH3);
13C NMR (50 MHz, CDCl3): l 164.3, 141.2, 140.8, 136.2,
133.3, 128.7, 128.5, 127.0, 124.5, 112.1, 109.3, 104.9, 83.1,
79.7, 76.8, 72.5, 67.5, 67.1, 26.5 (2C), 26.0, 24.8; EIMS
(M+−15): 450; HRMS calcd for C22H27NO10 (M+−15):
450.140021. Found: 450.142441.
mmol) were added and the contents were stirred at room
temperature for 2 days. Work-up and purification as
reported for 4a gave 5a (1.18 g, 87%) as a syrup.
[h]D=−2.4 (c 1.2, CHCl3); 1H NMR (200 MHz, CDCl3):
l 8.25 (d, 2H, J=7.5 Hz, Ar-H), 7.65 (d, 2H, J=7.5 Hz,
Ar-H), 6.3 (d, 1H, J=5.5 Hz, olefinic), 5.95 (s, 1H,
olefinic), 5.85 (d, 0.3H, J=3.75 Hz, H-1), 5.8 (d, 0.7H,
J=3.75 Hz, H-1), 5.7 (d, 1H, J=3.75 Hz, benzylic), 5.3
(s, 1H, H-3), 4.5 (d, 0.3H, J=3.75 Hz, H-2), 4.4 (d, 0.7H,
J=3.75 Hz, H-2), 4.2–3.98 (m, 4H, H-4, 5, 6, 6%), 3.45
(br.d, 0.3H, J=5.5 Hz, -OH), 3.13 (br.d, -OH, J=5.5 Hz,
0.7H), 1.6–1.25 (br.s, 12H, 4CH3); 13C NMR (50 MHz,
CDCl3): l 162.5, 148.75, 141.0, 127.42, 127.28, 123.35
(2C), 112.19, 109.32, 106.2, 104.82, 83.62, 79.65, 76.34,
74.76, 69.63, 67.13, 64.74, 26.9, 26.46, 26.25, 25.97.
HREIMS calcd for C22H27NO10 (M+−15): 450.140021.
Found: 450.1386.
4.5. 6-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
dimethyl-(3aS,4R,6R,6aS)-perhydrofuro [3,4-d][1,3]-
dioxol-4-yl 2-hydroxy(2-nitrophenyl)methylacrylate 4b
Method B: A mixture of 1 (0.20 g, 0.64 mmol), 5 (0.12
g, 0.76 mmol) and DABCO (0.014 g, 0.13 mmol) in
DMSO (1 mL) were stirred for 24 h at room temperature.
The reaction mixture was treated with water (20 mL),
brine (25 mL) and extracted into ether (3×25 mL), the
combined organic layers were washed with water (2×25
mL), dried (Na2SO4) and concentrated under reduced
pressure. The residue was purified by column chromatog-
raphy to afford 5a (0.28 g, 95%) as a syrup, which was
identical spectroscopically to 5a prepared by method A.
To a solution of 2 (0.20 g, 0.64 mmol) in THF (2 mL),
4 (0.12 g, 0.76 mmol) and DABCO (0.014 g, 0.13 mmol)
were added and the reaction was performed as reported
for 4a, to give 4b (0.26 g, 88%) as a syrup. [h]D=+15.1
(c 2.1, CHCl3); 1H NMR (200 MHz, CDCl3): l 7.98–7.9
(m, 1-H, Ar-H), 7.65 (d, 2H, J=4.18 Hz, Ar-H), 7.5–7.4
(m, 1H, Ar-H), 6.42 (br.s, 1H, olefinic), 6.08 (s, 1H, H-1),
6.1 (s, 1H, olefinic), 5.91 (br.s, 1H, benzylic), 4.81–4.72
(m, 1H, H-3), 4.61 (br.d, 0.7H, J=5.12 Hz, H-2), 4.42
(br.d, 0.3H, J=5.12 Hz, H-2), 4.12–3.9 (m, 2H, H-4, 5),
3.7 (d, 1H, J=4.65 Hz, H-6), 3.42 (d, 1H, J=3.72 Hz,
H-6%), 1.45 (s, 6H, 2CH3), 1.31 (s, 6H); EIMS (M+−15):
450; HRMS calcd for C22H27NO10 (M+−15): 450.140021.
Found: 450.137848.
4.8. 6-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
dimethyl-(3aS,4R,6R,6aS)-perhydrofuro [3,4-d][1,3]-
dioxol-4-yl 2-hydroxy(4-nitrophenyl)methylacrylate 5b
To a solution of 2 (0.20 g, 0.64 mmol) in THF (2 mL)
5 (0.12 g, 0.76 mmol) and DABCO (0.014 g, 0.13 mmol)
were added and the contents stirred for 2 days at room
temperature. Work-up and purification as for 4a gave 5b
(0.29 g, 86%) as a syrup. [h]D=+20.8 (c 1.83, CHCl3); 1H
NMR (200 MHz, CDCl3): l 8.24 (d, 2H, J=9.52 Hz,
Ar-H), 7.6 (d, 2H, J=7.61 Hz, Ar-H), 6.38 (d, 1H,
J=3.81 Hz, olefinic), 6.16 (s, 1H, olefinic), 6.0 (s, 0.7H,
H-1), 5.9 (s, 0.3H, H-1), 5.64 (s, 1H, benzylic), 4.8 (m,
1H, H-3), 4.62 (d, 1H, J=5.71 Hz, H-2), 4.38 (m, 1H,
H-4), 4.1–3.85 (m, 3H, H-5, 6, 6%), 3.2 (br. s, 0.3H, -OH),
3.1 (br. s, 0.7H, -OH), 1.45–1.3 (br. s, 12H, 4CH3). EIMS
(M+−15): 450; HREIMS calcd for C22H27NO10 (M+−15):
450.140021. Found: 450.137848.
4.6. 5-tert-Butyldimethylsilyloxymethyl-2,2-dimethyl-
(3aR,6S,6aR)-perhydrofuro [2,3-d][1,3]-dioxol-6-yl 2-
hydroxy(2-nitrophenyl)methylacrylate 4c
To a solution of 3 (0.31 g, 0.86 mmol) in THF (3 mL),
4 (0.16 g, 1.04 mmol) and DABCO (0.02 g, 0.17 mmol)
were added and the contents were stirred for 6 days at
room temperature. Work-up and purification as
described for 4a gave 4c (0.38 g, 85%) as a syrup.
[h]D=−2.5 (c 1.1, CHCl3); 1H NMR (200 MHz, CDCl3):
l 7.6 (m, 2H, Ar-H), 7.4 (br.s, 2H, Ar-H), 6.32 (s, 1H,
olefinic), 6.2 (s, 1H, olefinic), 5.82 (d, 0.3H, J=4.38 Hz,
H-1), 5.75 (s, 1H, benzylic), 5.6 (d, 0.7H, J=4.38 Hz,
H-1), 5.38 (d, 0.3H, J=3.41 Hz, H-3), 5.28 (d, 0.7H,
J=3.41 Hz, H-3), 4.44 (d, 0.3H, J=3.89 Hz, H-2), 4.23
(d, 0.7H, J=3.89 Hz, H-2), 3.82 (m, 1H, H-4), 3.74–3.62
(m, 2H, H-5, 5%), 3.3–3.18 (br.s, 1H, -OH), 1.5 (br. s, 3H,
-CH3), 1.3 (br. s, 3H, -CH3), 1.01 (s, 9H, -C(CH3)3), 0.12
(s, 6H, 2CH3); anal. calcd for C24H35NO9Si: C, 56.56; H,
6.92. Found: C, 56.23; H, 6.16%.
4.9. 5-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
dimethyl-(3aR,6S,6aR)-perhydrofuro [2,3-d][1,3]-dioxol-
6-yl 2-(1-hydroxy-3-methylbutyl)acrylate 6a
To a solution of 1 (0.20 g, 64 mmol) in THF (2 mL) 6
(0.05 mL, 0.76 mmol) and DABCO (0.014 g, 0.13 mmol)
were added and the contents were stirred for 20 h at room
temperature. Work-up and purification as reported for
1
4a afforded 6a (0.17 g, 67%) as a syrup. H NMR (200
4.7. 5-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
dimethyl-(3aR,6S,6aR)-perhydrofuro [2,3-d][1,3]-dioxol-
6-yl 2-hydroxy(4-nitrophenyl)methylacrylate 5a
MHz, CDCl3): l 6.22 (s, 1H, olefinic), 5.82 (d, 1H,
J=3.63 Hz, H-1), 5.78 (s, 1H, olefinic), 5.28 (br.s, 1H,
allylic), 4.48 (d, 1H, J=3.63 Hz, H-2), 4.18–3.92 (m, 5H,
H-3, 4, 5, 6, 6%), 2.28 (br.s, 1H, -OH), 1.95–1.85 (m, 1H,
Me2CH-), 1.5 (s, 3H, CH3), 1.4 (s, 3H, CH3), 1.29 (br.s,
6H, 2CH3), 0.95–0.85 (2d, 6H, J=5.45, 5.9 Hz); EIMS
Method A: To a solution of 1 (0.92 g, 2.92 mmol) in THF
(6 mL) 5 (0.53 g, 3.51 mmol) and DABCO (0.07 g, 0.58

P. Radha Krishna et al. / Tetrahedron: Asymmetry 12 (2001) 829–837
835
(M+−15): 371; HREIMS calcd for C19H30O8 (M+−15):
4.13. 5-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
371.170593. Found: 371.171901.
dimethyl-(3aR,6S,6aR)-perhydrofuro [2,3-d][1,3]-dioxol-
6-yl 2-hydroxy(2-nitro-5-n-propoxyphenyl)-
methylacrylate 9a
4.10. 6-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
dimethyl-(3aS,4R,6R,6aS)-perhydrofuro [3,4-d][1,3]-
dioxol-4-yl 2-(1-hydroxy-3-methylbutyl)acrylate 6b
To a solution of 1 (0.10 g, 0.32 mmol) in THF (2
mL) 9 (0.73 g, 0.35 mmol) and DABCO (0.007 g,
0.06 mmol) were added and the contents were stirred
at room temperature for 4 days. Work-up and purifi-
cation as reported for 4a afforded 9a (0.16 g, 95%) as
To a solution of 2 (0.15 g, 0.48 mmol) in THF (2
mL) 6 (0.05 ml, 0.57 mmol) and DABCO (0.011 g,
0.095 mmol) were added and the contents were
stirred at room temperature for 20 h. Work-up and
purification as reported for 4a afforded 6b (0.14 g,
76%) as a syrup. 1H NMR (200 MHz, CDCl3): l
6.41 (d, 1H, J=1.0 Hz, olefinic), 6.14 (s, 1H,
olefinic), 5.91 (s, 1H, H-1), 5.32 (s, 1H, allylic), 4.8–
4.7 (m, 1H, H-3), 4.55 (d, 1H, J=5.0 Hz, H-2), 4.35–
4.28 (m, 1H, H-4), 4.15–3.95 (m, 3H, H-5, 6, 6%), 2.3
(br.s, 1H, -OH), 1.92–1.80 (m, 1H, Me2CH-), 1.5–
1.22 (br.s, 12H, 4CH3), 0.98–082 (2d, 6H, J=5.5, 6.0
Hz, Me2CH-); EIMS (M+−15): 371; HREIMS calcd
1
a thick syrup. [h]D=−33.5 (c 1.15, CHCl3); H NMR
(200 MHz, CDCl3): l 8.1 (d, 1H, J=3.72 Hz, Ar-H),
7.3 (m, 1H, Ar-H), 6.89 (br.d, 1H, Ar-H), 6.3 (br.d,
2H, J=8.83 Hz, olefinic), 5.85 (d, 0.57H, J=3.72 Hz,
H-1), 5.78 (d, 0.43H, J=3.72 Hz, H-1), 5.62 (s,
0.57H, benzylic), 5.42 (s, 0.43H, benzylic), 5.32 (d,
1H, J=3.72 Hz, H-3), 4.5 (d, 1H, J=4.18 Hz, H-2),
4.2 (br.s, 1H, H-4), 4.2–3.9 (m, 5H, H-5, 6, 6, -CH2-),
3.4 (br.s, 1H, -OH), 1.85 (m, 2H, -CH2-), 1.5 (s, 3H,
CH3), 1.45–1.25 (br.s, 9H, 3CH3), 1.09 (t, 3H, J=8.5
Hz, CH3); 13C NMR (50 MHz, CDCl3): l 164.6,
141.6, 141.1, 139.0 (2C), 127.7, 126.7, 114.1, 113.6,
112.2, 109.3, 105.0, 83.2, 79.9, 76.7, 72.2, 70.2, 67.6,
67.5, 26.7 (2C), 26.1, 25.1, 22.2, 10.3; FABMS (M+);
523. Anal. calcd for C25H33NO11: C, 57.36; H, 6.35.
Found. C, 56.97; H, 6.62%.
for
371.171056.
C19H30O8
(M+−15):
371.170593.
Found:
4.11. 5-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
dimethyl-(3aR,5R,6S,6aR)-perhydrofuro [2,3-d][1,3]-
dioxol-6-yl 2-hydroxy(phenyl)methylacrylate 7a
4.14. 5-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
dimethyl-(3aR,6S,6aR)-perhydrofuro [2,3-d][1,3]-dioxol-
6-yl 2-hydroxy(5-methoxy-2-nitrophenyl)methylacrylate
10a
To a solution of 1 (0.50 g, 1.59 mmol) in THF (5
mL) 7 (0.20 g, 1.90 mmol) and DABCO (0.035 g,
0.32 mmol) were added and the contents were stirred
at room temperature for 6 days. Work-up and purifi-
cation as reported for 4a gave 7a (0.60 g, 90%) as a
syrup. [h]D=−27.5 (c 1, CHCl3); 1H NMR (200
MHz, CDCl3): l 7.3–7.21 (m, 5-H, Ar-H), 6.44 (s,
1H, olefinic), 5.92 (s, 1H, olefinic), 5.88 (d, 1H, J=
4.0 Hz, H-1), 5.6 (s, 1H, benzylic), 4.78 (s, 1H, H-3),
4.59 (d, 1H, J=4.5 Hz, H-2), 4.35 (m, 1H, H-4),
4–3.84 (m, 3H, H-5, 6, 6%), 3.12 (br.s, 1H, -OH),
1.42–1.31 (br.s 12H, 4 CH3); MSEI (M+−15): 405;
anal. calcd for C22H28O8: C, 62.85; H, 6.7. Found: C,
62.61; H, 6.3%.
To a solution of 1 (0.10 g, 0.32 mmol) in THF (2
mL) 10 (0.07 g, 0.38 mmol) and DABCO (0.007 g,
0.06 mmol) were added and the contents were stirred
at room temperature for 4 days. Work-up and purifi-
cation as for 4a afforded 10a (0.14 g, 92%) as a thick
syrup. [h]D=−9.8 (c 0.65, CHCl3); 1H NMR (400
MHz, CDCl3) l 8.08 (m, 1H, Ar-H), 7.3 (m, 1H,
Ar-H), 6.85 (s, 1H, Ar-H), 6.25 (s, 2H, olefinic), 5.8
(d, 0.62H, J=1.97 Hz, H-1), 5.78 (d, 0.38H, J=1.97
Hz, H-1), 5.58 (s, 1H, benzylic), 5.3 (s, 0.62H, H-3),
5.22 (s, 0.38H, H-3), 4.5 (d, 1H, J=1.97 Hz, H-2),
4.18 (s, 1H, H-4), 4.1 (m, 1H, H-5), 3.96 (m, 2H,
H-6, 6%), 3.9 (s, 3H, -OMe), 1.5 (s, 3H, CH3), 1.4–1.2
(br.s, 9H, 3CH3); FABMS (M+): 495. Anal. calcd for
C23H29NO11: C, 55.75; H, 5.90. Found: C, 55.35; H,
5.85%.
4.12. 5-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-2,2-
dimethyl-(3aR,6S,6aR)-perhydrofuro [2,3-d][1,3]-dioxol-
6-yl 2-[2,3-dichlorophenyl(hydroxy)methyl]acrylate 8a
To a solution of 1 (0.20 g, 0.64 mmol) in THF (2
mL) 8 (0.13 g, 0.76 mmol) and DABCO (0.014 g,
0.13 mmol) were added and the contents were stirred
at room temperature for 2 days. Work-up and purifi-
cation as reported for 4a gave 8a (0.30 g, 97%) as a
thick syrup. 1H NMR (200 MHz, CDCl3): l 7.57.4
(m, 2H, Ar-H), 7.25 (s, 1H, Ar-H), 6.32 (d, 1H, J=
5.36 Hz, olefinic), 5.95 (s, 1H, olefinic), 5.88 (d, 0.5H,
J=2.92 Hz, H-1), 5.79 (d, 0.5H, J=2.92 Hz, H-1),
5.61 (s, 0.5H, H-3), 5.4 (s, 0.5H, H-3), 5.33 (s, 0.5H,
benzylic), 5.27 (s, 0.5H, benzylic), 4.5 (d, 1H, J=3.41
Hz, H-2), 4.22–3.9 (m, 4H, H-4, 5, 6, 6%), 1.5 (s, 3H,
-CH3), 1.45–1.2 (br.s, 9H, 3CH3); (M+−15) 473;
4.15. Ethyl-2-hydroxy(4-nitrophenyl)methylacrylate 12
Method A: To a stirred solution of 5a (0.20 g, 0.43
mmol) in DME (2 mL) was added aq. LiOH (1N,
0.05 g, 2.14 mmol) and stirred for 2 h. The reaction
mixture was taken in EtOAc (10 mL), washed with
dil. HCl (5 mL) and water (10 mL). The combined
organic layers were dried (Na2SO4) and evaporated
under reduced pressure. The residue was purified by
column chromatography (silica gel, hexane:EtOAc,
3:1) to afford (4-nitrophenyl) 2-hydroxy methylacrylic
acid 11 (0.082 g, 86%) as a syrup. 1H NMR (200
MHz, CDCl3): l 8.2 (d, 2H, J=8.78 Hz, Ar-H), 7.58
(d, 2H, J=9.26 Hz, Ar-H), 6.49 (s, 1H), 5.93 (s, 1H),
5.6 (s, 1H).
HREIMS
calcd
for
C22H26Cl2O8
(M+−15):
473.076111. Found: 473.076998.

836
P. Radha Krishna et al. / Tetrahedron: Asymmetry 12 (2001) 829–837
To a stirred solution of 11 (0.10 g, 0.44 mmol) in
CH2Cl2 (2 mL) containing DMAP (5 mg), absolute
ethanol (1 mL) and DCC (0.09 g, 0.45 mmol) were
added at 0°C and stirred for 2 h at 20°C. The reaction
mixture was filtered off and washed with CH2Cl2 (5
mL). The filtrate was evaporated under reduced pres-
sure, the residue taken in CH2Cl2 (5 mL) and washed
with 0.5N HCl (5 mL) and saturated NaHCO3 (5 mL).
The organic layers were dried (Na2SO4) and evaporated
under reduced pressure. The residue was purified by
column chromatography (silica gel, hexane:EtOAc,
8.5:1.5) to afford 12 (0.11 g, 95%) as a syrup. HPLC: rt,
30.2 (68.8%), 31.6 (30.5%). [h]D=+6.4 (c 0.3, CHCl3);
1H NMR (200 MHz, CDCl3): l 8.2 (d, 2H, J=8.3 Hz,
Ar-H), 7.56 (d, 2H, J=8.83 Hz, Ar-H), 6.35 (s, 1H), 5.8
(s, 1H), 5.55 (s, 1H), 4.25–4.1 (q, 2H, -CH2), 3.25 (br.s,
1H, -OH), 1.3–1.2 (s, 3H, -CH3); EIMS (M+): 251;
HREIMS calcd for C12H13NO5 (M+): 251.079373.
Found: 251.080030.
h at room temperature. The precipitate was filtered
through a pad of Celite and washed with ether (25 mL).
The ether layer was washed with saturated NaHCO3
(10 mL), brine (10 mL), dried (Na2SO4), evaporated
and the resulting residue was purified by column chro-
matography (silica gel, hexane: EtOAc, 8.5:1.5). First
eluted was (R)-12 (0.08 g, 40%) as a syrup, [h]D=+16.2
(c 0.5, CHCl3), HPLC: rt, 27.2 (97%). Second eluted
was epoxy alcohol 13 (0.09 g, 41%) as a syrup. [h]D=−
1
15.1 (c 0.6, CHCl3); H NMR (200 MHz, CDCl3): l 8.2
(d, 2H, J=9.0 Hz, Ar-H), 7.64 (d, 2H, J=10.0 Hz,
Ar-H), 5.3 (d, 1H, J=6.0 Hz, benzylic), 4.15 (q, 2H,
-CH2-), 3.15 (d, 2H, J=7.0 Hz, epoxy), 2.92 (d, 1H,
J=7.5 Hz, -OH), 1.24 (t, 3H, J=7.5 Hz, -CH3). Anal.
calcd for C12H13NO6: C, 53.93; H, 4.9. Found: C,
53.61; H, 4.22%.
4.18. Kinetic resolution of ( )-12 with (−)-DIPT
Sharpless kinetic resolution of ( )-12 (0.30 g, 1.1 mmol)
as in the previous experiment with (−)-DIPT (0.07 g,
0.30 mmol), TIP (0.07 mL, 0.24 mmol) and cumenehy-
droperoxide (0.13 mL, 0.72 mmol) after column chro-
matography, first afforded (S)-12 (0.15 g, 44%) as a
syrup, [h]D=−12.2 (c 0.8, CHCl3); HPLC: rt, 31 (75%).
Second eluted was epoxy alcohol 14 (0.11 g, 34%) as a
syrup. [h]D=+19.1 (c 0.7, CHCl3). Anal. calcd for
C12H13NO6. Found: C, 53.58; H, 4.57%.
Method B: To a stirred solution of 5b (0.25 g, 0.54
mmol) in DME (2 mL) was added 1N aq. LiOH (0.06
g, 2.68 mmol) and the mixture was stirred for 2 h. The
reaction mixture was taken in EtOAc (10 mL), washed
with dil. HCl (5 mL) and water (10 mL). Work-up and
purification as reported in the previous experiment gave
11 (0.11 g, 91%), which was esterified with DMAP (5
mg), absolute ethanol (1 mL) and DCC (0.09 g, 0.45
mmol) at 0°C. Work-up and purification as reported in
the previous experiment resulted in 12 (0.11 g, 94%),
whose spectral data were comparable in all respects
with the sample prepared earlier including rotation and
HPLC.
4.19. Ethyl-2-hydroxy(2-nitrophenyl)methylacrylate 16
To a solution of 4a (0.10 g, 0.22 mmol) in DME (2 mL)
was added LiOH (0.024 g, 1.07 mmol) and the mixture
was stirred for 2 h. Work-up and purification as
described for 11 gave 2-hydroxy(2-nitrophenyl)methyl-
4.16. Synthesis of ( )-ethyl-2-hydroxy(4-nitrophenyl)-
methylacrylate 12
1
acrylic acid (15; 0.05 g, 96%) as a syrup. H NMR (200
MHz, CDCl3): l 7.9 (br.d, 1H, J=7.0 Hz, Ar-H), 7.78
(t, 1H, Ar-H), 7.69 (t, 1H, Ar-H), 7.53–7.44 (m, 1H,
Ar-H), 6.52 (s, 1H, olefinic), 6.18 (s, 1H, olefinic), 5.85
(s, 1H, benzylic).
To a stirred solution of 4-nitro benzaldehyde 5 (1.0 g,
6.62 mmol) in dry THF (6 mL) were added DABCO
(0.15 g, 1.32 mmol), ethyl acrylate (0.8 mL, 7.28 mmol)
and the mixture was stirred for 24 h. Solvent was
removed and the residue was purified by column chro-
matography (silica gel, hexane:EtOAc, 8.5:1.5) to
afford the adduct ( )-12 (1.62 g, 97%) as a syrup,
whose spectral data were identical with 12 prepared
earlier.
To a solution of 15 (0.10 g, 0.44 mmol) in CH2Cl2 (2
mL) were added DCC (0.09 g, 0.45 mmol), DMAP (5
mg) and EtOH (2 mL) and the mixture was stirred for
2 h at 20°C. Work-up and purification as described for
12 gave 16 (0.11 g, 96%) as a syrup. [h]D=+3.7 (c 0.5,
1
CHCl3); H NMR (200 MHz CDCl3): l 7.98 (d, 1H,
4.17. Kinetic resolution of ( )-ethyl 2-hydroxy(4-nitro-
J=8.09 Hz, Ar-H), 7.78 (d, 1H, J=7.62 Hz, Ar-H),
7.68 (t, 1H, Ar-H), 7.51 (t, 1H, Ar-H), 6.38 (s, 1H,
olefinic), 6.19 (s, 1H, olefinic), 5.75 (s, 1H, benzylic),
4.19 (q, 2H, -CH2-), 3.48 (br.s, 1H, -OH), 1.28 (t, 3H,
J=8.57 Hz, -CH3). Anal. calcd for C12H13NO5: C,
57.37, H, 5.22. Found: C, 57.30; H, 5.18%.
phenyl)methylacrylate 12 with (+)-DIPT
,
To a stirred suspension of activated 4 A MS (0.30 g) in
CH2Cl2 (5 mL) was added Ti(OPri)4 (0.045 g, 0.15
mmol) at room temperature, the mixture was cooled to
−20°C and treated with (+)-DIPT (0.046 g, 0.20 mmol)
in CH2Cl2 (1 mL). After 30 min a solution of ( )-12
(0.20 g, 0.79 mmol) in CH2Cl2 (4 mL) was added
dropwise and stirred for 1 h. Cumenehydroperoxide
(0.07 mL, 0.47 mmol) was added slowly and stirred for
20 h at −20°C. The reaction mixture was quenched with
Me2S (0.07 mL, 1.03 mmol) and the mixture was stirred
for 30 min at the same temperature. To this mixture
were sequentially added 10% aq. tartaric acid (1 mL),
NaF (3 g) and the mixture was vigorously stirred for 3
4.20. 2-Hydroxy(phenyl)methylacrylic acid 17
To a solution of 7a (0.20 g, 0.48 mmol) in DME (3 mL)
was added LiOH (0.06 g, 2.38 mmol) and stirred for 2
h, work-up and purification as described for 11 gave 17
1
(0.08 g, 94%) as a syrup. [h]D=−1.2 (c 0.4, CHCl3); H
NMR (CDCl3): l 7.35 (m, 5H, Ar-H), 6.32 (s, 1H,
olefinic), 5.78 (s, 1H, olefinic), 5.5 (s, 1H, benzylic), 2.96
(br.s, 1H, -OH).

P. Radha Krishna et al. / Tetrahedron: Asymmetry 12 (2001) 829–837
837
5. Yang, K.-S.; Chen, K. Org. Lett. 2000, 2, 729–731.
6. Barrett, A. G. M.; Cook, A. S.; Kamimura, A. J. Chem.
4.21. Ethyl 2-[2-nitro-5-propoxyphenyl(hydroxy)methyl]-
acrylate 19
Soc., Chem. Commun. 1999, 2533–2534.
7. Iwabuchi, Y.; Nakatani, M.; Yokoyama, N.;
Hatakeyama, S. J. Am. Chem. Soc. 1999, 121, 10219–
10220.
To a solution of 9a (0.15 g, 0.29 mmol) in DME (2 mL)
was added LiOH (0.04 g, 1.47 mmol) and the mixture
was stirred at room temperature for 2 h, work-up and
purification as described for 11 gave 2-[2-nitro-5-pro-
poxyphenyl(hydroxy)methyl]acrylic acid (18; 0.07 g,
8. Gilbert, A.; Heritage, T. W.; Isaacs, N. S. Tetrahedron:
Asymmetry 1991, 2, 969–972.
9. Hayase, T.; Shibata, T.; Soai, K.; Wakatsuki, Y. J.
Chem. Soc., Chem. Commun. 1998, 1271–1272.
10. Kataoka, T.; Iwama, T.; Kinoshita, H.; Tsujiyama, S.;
Tsujiyama, S.; Tsurukami, Y.; Iwamura, T.; Watanabe,
S. Synlett 1997, 956–961.
1
94%) as a syrup. H NMR (CDCl3): l 8.1 (br.d, 1H,
J=10 Hz, Ar-H), 7.28 (d, 1H, J=4.5 Hz, Ar-H), 6.91
(d, 1H, J=1.5 Hz, Ar-H), 6.41 (s, 1H, olefinic), 5.62 (s,
1H, olefinic), 5.33 (s, 1H, benzylic), 4.06 (t, 2H, J=7.5
Hz, -CH2-O-), 3.5 (br.s, 1H, -OH), 1.87–1.78 (m, 2H,
-CH2), 1.13 (t, 3H, J=8.0 Hz, -CH3).
11. Oishi, T.; Oguri, H.; Hirama, M. Tetrahedron: Asymme-
try 1995, 6, 1241–1244.
12. Sharma, G. V. M.; Hymavathi, L.; Radha Krishna, P.
Tetrahedron Lett. 1997, 38, 6929–6932.
13. Sharma, G. V. M.; Subash Chander, A.; Krishnudu, K.;
Radha Krishna, P. Tetrahedron Lett. 1997, 38, 9051–
9054.
14. Sharma, G. V. M.; Goverdhan Reddy, V.; Radha
Krishna, P. Tetrahedron Lett. 1999, 40, 1783–1786.
15. Sharma, G. V. M.; Goverdhan Reddy, V.; Radha
Krishna, P. Tetrahedron: Asymmetry 1999, 10, 3777–
3784.
16. Sharma, G. V. M.; Srinivasa Reddy, I.; Goverdhan
Reddy, V.; Rama Rao, A. V. Tetrahedron: Asymmetry
1999, 10, 229–235.
To a solution of 18 (0.10 g, 0.37 mmol) in CH2Cl2 (2
mL) were added DCC (0.08 g, 0.37 mmol), DMAP (5
mg) and EtOH (2 mL) and the mixture was stirred for
2 h at 20°C. Work-up and purification as described for
12 gave 19 (0.11 g, 95%) as a syrup. [h]D=−3.31 (c
0.25, CHCl3); 1H NMR (CDCl3): l 8.1 (br.d, 1H,
J=10.0 Hz, Ar-H), 7.28 (d, 1H, J=4.50 Hz, Ar-H),
6.92 (d, 1H, J=1.5 Hz, Ar-H), 6.4 (s, 1H, olefinic), 5.6
(s, 1H, olefinic), 5.32 (s, 1H, benzylic), 4.28 (q, 2H),
4.05 (t, 2H, J=7.5 Hz, -CH2-O-), 3.5 (br.s, 1H, -OH),
1.86 (m, 2H, -CH2-), 1.32 (t, 3H, J=4.0 Hz, -CH3), 1.11
(t, 3H, J=8.0 Hz, -CH3). Anal. calcd for C15H19NO6:
C, 58.25; H, 6.19. Found: C, 58.11; H, 6.06%.
17. Aggarwal, V. K.; Mereu, A. J. Chem. Soc., Chem. Com-
mun. 1999, 2311–2312.
18. Miyakoshi, T.; Omichi, H.; Saito, S. Nippon Kagaku
Kaishi 1979, 748.
19. Neises, B.; Steglich, W. Angew. Chem., Int. Ed. Engl.
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