Enantioselective reduction of prochiral ketones employing sprouted Pisum sativa as biocatalyst

Article abstract of DOI:10.1055/s-0028-1088047

Sprouted green peas have been used for the first time as biocatalysts for enantioselective reduction of prochiral ketones. The reactions are highly enantioselective to furnish chiral alcohols in good yields. The sprouted peas as biocatalysts are a cheap and easy way for generating some interesting chiral alcohols. This process is efficient and convenient to produce chiral secondary alcohols in water. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1088047

PAPER
1881
Enantioselective Reduction of Prochiral Ketones Employing Sprouted Pisum
sativa as Biocatalyst
E
nantiosel
h
e
ctive Reduc
i
tionof
l
P
rochi
l
ral Ke
t
u
one
s
w
itha Biocata
S
lyst . Yadav,* Basi V. Subba Reddy, Chittamuru Sreelakshmi, Adari Bhaskar Rao
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: yadavpub@iict.res.in
Received 19 January 2009; revised 3 February 2009
OH
Me
O
Abstract: Sprouted green peas have been used for the first time as
biocatalysts for enantioselective reduction of prochiral ketones. The
Pisum sativa
Me
reactions are highly enantioselective to furnish chiral alcohols in
good yields. The sprouted peas as biocatalysts are a cheap and easy
way for generating some interesting chiral alcohols. This process is
efficient and convenient to produce chiral secondary alcohols in wa-
ter.
buffer (pH 7.0), r.t.
1
(S)-2a
Scheme 1
Key words: biocatalysis, ketones, enantioselective, chiral alcohols
(2a) in 72% yield with 98% ee (Scheme 1). The bioreduc-
tion of the keto group was performed using dried green
peas obtained from super market. Similarly, various sub-
stituted acetophenones were converted into their chiral
secondary alcohols with high degree of enantioselectivity
(Table 1, entries b–g). The corresponding S-alcohols were
obtained in all cases, with enantiomeric excesses ranging
from 91–98%. The effects of ring substituents on the re-
duction of substituted acetophenones by P. sativa are
quite general. With aryl methyl ketones, it was observed
that electron-donating substituents slowed the reaction,
highlighting the sensitivity of bioreduction kinetics to
electronic effects, which is in accordance with results re-
ported in the literature.9Whencompared to aryl methyl ke-
tones, cyclic and acyclic ketones gave the products
relatively in low yields and with moderate enantioselec-
tivity (Table 1, entries h–k).
Biocatalysts are very useful for the preparation of chiral
drugs, fragrances, and pheromones. In recent years, the
application of enzymes as biocatalysts in organic synthe-
sis is quite well known.1 Asymmetric reduction of
prochiral ketones is an essential transformation in organic
synthesis owing to the presence of secondary alcohols in
biologically active natural products. In recent years, sec-
ondary chiral alcohols have received great commercial
importance because of their numerous applications.2 They
are being used as drug intermediates in pharmaceuticals
and as toxophore in agrochemicals. These chiral synthons
can be produced by economically viable and eco-friendly
manner by using biocatalysts such as lipase, horse liver
dehydrogenase, yeast (Geotricum candidum), etc.3 Re-
cently, plants have been considered as suitable biochemi-
cal systems for the biotransformation of organic
xenobiotics such as monoterpenes, aliphatic ketones, and
aromatic ketones.4,5 Both immobilized plant cell cultures6
and whole plant tissues have been utilized for the stereo-
selective reduction of ketones.7,8 Recently, vegetables
such as Daucas carota root and green grams have been
used as biocatalysts for the enantioselective reduction of
prochiral ketones to furnish chiral secondary alcohols.9,10
However, in some cases, no reduction was observed with
b-keto esters and also require large excess of biomass to
achieve acceptable yields.
Next, we examined the reduction of 2-aryltetrahydro-2H-
pyran-4-one. The reduction of ( )-2-(4-chlorophenyl)tet-
rahydro-2H-pyran-4-one with green peas in water gave
(2S,4S)-2-(4-chlorophenyl)tetrahydropyranol
and
(2R,4S)-2-(4-chlorophenyl)tetrahydropyranol in a 1:1 ra-
tio (Scheme 2).
O
O
OH
OH
Pisum sativa
+
buffer (pH 7.0), r.t.
Ar
Ar
O
O
Ar
(±)
In this report, we describe an enzymatic approach for the
preparation of chiral secondary alcohols in highly enanti-
oselective manner by means of reduction of prochiral ke-
tones using sprouted Pisum sativa in water.
Ar = 4-chlorophenyl
(–)-(2S,4S)-3l
(+)-(2R,4S)-4l
Scheme 2
The stereoisomers could be easily separated by column
chromatography. The enantiomeric excesses of both the
cis- and trans-tetrahydropyranols were determined by
HPLC using chiral columns and were higher than 87%.
Initially, we attempted the reduction of acetophenone (1)
with sprouted green peas in water. The reduction occurred
at room temperature to furnish (S)-1-phenethyl alcohol
1
The structures of the products were established by H
NMR, IR, and mass spectrometry, and also by comparison
SYNTHESIS 2009, No. 11, pp 1881–1885
Advanced online publication: 14.04.2009
DOI: 10.1055/s-0028-1088047; Art ID: Z01109SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
9
with authentic samples.11 The absolute stereochemistry of
(2S,4S)-
and
(2R,4S)-2-aryltetrahydropyranols

1882
J. S. Yadav et al.
PAPER
(Scheme 2) was established by comparison with authentic 70% yield. Reduction occurs from the re-face only of the
samples.11 The use of green peas in water offers several prochiral ketone, independently of the configuration of
advantages compared to Baker’s yeast, such as low cost, the 2-aryl-substituted stereocenter. The stereochemical
ease of availability of the biocatalyst, simple workup and course of many bioreductions of ketones may be predicted
product recovery. The reductions in water gave the best from a simple model, which is generally referred to as
results. No specific match/mismatch effect from the adja- Prelog’s rule.12 This empirical model, originally designed
cent stereocenter was observed, as can be seen from the for the reduction of ketones by the fungus Curvularia
reduction of ( )-2-aryltetrahydropyran-4-one (Table 1, falcata implies that the outcome is mainly dependent on
entries l and m). At 100% conversion, equal amounts of the steric requirements of the substrate (Figure 1).
enantiopure tetrahydropyranols 3l and 4l were isolated in
Table 1 Reduction of Prochiral Ketones to Chiral Alcohols Using Germinated Green Peas in Water
25
Entry
Prochiral ketone
Producta
Time
(h)
[a]D
Yield
(%)c
ee
Configuration
(CHCl3)b
(%)d
O
OH
Me
a
24
72
32
72
–29.0
–10.2
–17.2
–23.2
72
60
55
63
98
93
94
91
S
Me
O
OH
b
c
d
e
f
S
S
S
S
S
S
Me
Me
Me
HO
CI
HO
O
OH
Me
CI
O
OH
Me
Me
MeO
O2N
MeO
O2N
O
OH
48
48
48
–27.7
–39.5
–12.6
71
65
68
95
91
92
Me
Me
O
OH
Me
Me
Me
Me
O
OH
Me
g
Me
Br
Br
O
OH
O
OMe
OH
O
h
i
72
58
+14.1
+21.4
45
42
89
88
1R,2S
OMe
O
S
O
OH
j
72
+15.7
40
87
S
Synthesis 2009, No. 11, 1881–1885 © Thieme Stuttgart · New York

PAPER
Enantioselective Reduction of Prochiral Ketones with a Biocatalyst
1883
Table 1 Reduction of Prochiral Ketones to Chiral Alcohols Using Germinated Green Peas in Water (continued)
25
Entry
Prochiral ketone
Producta
Time
(h)
[a]D
Yield
(%)c
ee
Configuration
(CHCl3)b
(%)d
O
OH
k
72
24
–12.8
–21.4
38
35
80
91
R
O
O
OH
O
l
2S,4S
2R,4S
CI
CI
OH
O
+15.7
35
93
CI
O
OH
m
24
–21.2
+18.6
33
32
87
92
2S,4S
2R,4S
O
O
OH
O
a All products were characterized by IR and NMR spectroscopy and mass spectrometry.
b c = 1.0.
c Yield refers to pure products after chromatography.
d Enantiomeric excesses of alcohols were determined using chiral HPLC.
In summary, the enantioselective reduction of a series of
prochiral ketones was achieved using sprouted green peas
in aqueous buffer pH 7.0, which gave the corresponding
S-alcohols with ee varying from 80–98%. The low cost
and the easy availability of the biocatalyst besides the ex-
perimental simplicity suggest the possible use of the
present method for large scale preparations of important
optically pure secondary alcohols.
O
HO
H
L
S
L
S
L = large group; S = small group
Figure 1 Model depicting stereochemical outcome of the bioreduc-
tion
The observed enantioselectivity is in accordance with Pre-
log’s rule. The presence of several competing oxidoreduc-
tases with opposite stereoselectivities in the plant tissues
may be the origin of the stereochemical outcome with
these substrates. Hence, this biocatalytic approach is
found to be suitable for the preparation of a wide range of
chiral secondary alcohols. The results are summarized in
Table 1. Finally; the recovered peas were used three times
with gradual decrease in conversion. For example, treat-
ment of 1 mmol of acetophenone with 25 grams of sprout-
ed seeds of green peas for 24 hours gave 72, 65, 57%
yields over three cycles. After three cycles, the recovered
biomass was used as manure.
Melting points were recorded on a Buchi R-535 apparatus and are
uncorrected. IR spectra were recorded on a Perkin-Elmer FT-IR
240-c spectrophotometer using KBr optics. NMR spectra were re-
corded on a Gemini-200 spectrometer (200 MHz for 1H NMR, 50
MHz for 13C NMR) in CDCl3 using TMS as an internal standard.
Mass spectra were recorded on a Finnigan MAT 1020 mass spec-
trometer operating at 70 eV. Column chromatography was per-
formed using F Merck 100–200 mesh silica gel. The enantiomeric
excess of the product was determined using a Shimadzu HPLC sys-
tem equipped with a chiral HPLC column (Chiralcel OD) and a UV
detector (254 nm). A solvent system of n-hexane and isopropanol
(8:2) at a flow rate of 1.0 mL/min was used. Optical rotations were
measured on a Perkin-Elmer model 341 digital polarimeter. The ab-
solute configuration of the products was determined by optical ro-
tation/chiral HPLC and was compared with literature values.8a
Synthesis 2009, No. 11, 1881–1885 © Thieme Stuttgart · New York

1884
J. S. Yadav et al.
PAPER
IR (neat): 3450, 2925, 2858, 1460, 1248, 1044, 758, 674 cm–1.
Preparation of Sprouted Green Peas
Dried green peas (10 g) obtained from a local market were soaked
in H2O (75 mL) for 7–8 h. The resulting soaked wet seeds were
tightly wrapped with porous cloth for 24 h at r.t. to obtain sprouts.
The gradated seeds (25 g of wet sprouted seeds) were used for the
bioreduction.
1H NMR (300 MHz, CDCl3): d = 8.10 (d, J = 8.3 Hz, 2 H), 7.48 (d,
J = 8.3 Hz, 2 H), 4.95 (q, J = 6.7 Hz, 1 H), 2.92 (br s, 1 H, OH), 1.47
(d, J = 6.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 25.3, 69.3, 123.6, 126.0, 147.0,
153.1.
MS: m/z = 190 (M+ + Na).
Bioreduction of Prochiral Ketones with Sprouted Peas; General
Procedure
The reduction was initiated by adding sprouted seeds of green peas
(25 g) to the prochiral ketone (1 mmol) dissolved in H2O (50 mL).
The reaction mixture was incubated in an orbital shaker at 25 °C. On
optimal conversion, the reaction was stopped and the mixture was
filtered off and the seeds were washed with H2O (3 ×). The filtrates
were extracted with EtOAc and the combined organic layers were
dried (Na2SO4), filtered, and evaporated. The crude products were
purified by flash chromatography to furnish the corresponding
chiral secondary alcohols. The reduction was also carried out on a
10 gram scale under similar conditions.
(S)-1-(p-Tolyl)ethanol (2f)
[a]D25 –39.5 (c 1.0, CHCl3).
IR (neat): 3352, 2974, 2925, 1574, 1428, 1200, 1076, 785, 696 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.48 (d, J = 8.8 Hz, 2 H), 7.12 (d,
J = 8.3 Hz, 2 H), 5.08 (q, J = 5.8 Hz, 1 H), 2.33 (s, 3 H), 2.05 (br s,
1 H, OH), 1.44 (d, J = 5.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 25.0, 29.6, 69.5, 123.4, 125.5,
127.3, 129.6, 134.1, 147.7.
MS: m/z = 136 (M+).
(S)-1-Phenylethanol (2a)
[a]D25 –29.0 (c 1.0, MeOH).
(S)-1-(4-Bromophenyl)ethanol (2g)
[a]D25 –12.6 (c 1.0, CHCl3).
IR (neat): 3357, 2973, 1489, 1081, 1009, 824, 534 cm–1.
IR (neat): 3359, 3030, 2974, 2927, 1493, 1451, 1369, 1203, 1010,
760, 699, 539 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.45 (d, J = 8.3 Hz, 2 H), 7.20 (d,
J = 8.3 Hz, 2 H), 4.80 (q, J = 6.0 Hz, 1 H), 2.50 (br s, 1 H, OH), 1.50
(d, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 145, 131, 127, 121, 70, 25.
MS: m/z = 223 (M – H + Na+).
1H NMR (200 MHz, CDCl3): d = 7.39–7.15 (m, 5 H), 4.80 (q,
J = 6.6 Hz, 1 H), 2.77 (br s, 1 H, OH), 1.41 (d, J = 6.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 24.9, 69.7, 125.1, 126.9, 128.09,
145.7.
MS: m/z = 123 (M+ + H).
Methyl (1R,2S)-2-Hydroxycyclopentanecarboxylate (2h)
[a]D25 +14.1 (c 0.5, CHCl3).
IR (neat): 3435, 2924, 2854, 1629, 1460, 1265, 758 cm–1.
(S)-4-(1-Hydroxyethyl)phenol (2b)
[a]D25 –10.2 (c 1.0, EtOH).
IR (neat): 3354, 2972, 2926, 1457, 1370, 1284, 1126, 1076, 896,
760, 729, 458 cm–1.
1H NMR (200 MHz, CDCl3): d = 4.09 (t, J = 6.0 Hz, 1 H), 3.86 (s,
1H NMR (200 MHz, CDCl3): d = 7.87 (d, J = 8.2 Hz, 2 H), 6.89 (d,
J = 8.2 Hz, 2 H), 4.83 (q, J = 6.6 Hz, 1 H), 1.95 (br s, 1 H, OH), 1.48
(d, J = 6.6 Hz, 3 H).
3 H), 2.36–2.19 (m, 1 H), 2.16–2.02 (m, 2 H), 1.96–1.64 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 21.9, 27.1, 34.1, 51.8, 52.5, 96.1,
175.3.
13C NMR (75 MHz, CDCl3): d = 24.6, 70.3, 115.4, 126.9, 131.1,
155.4.
MS: m/z = 167 (M+ + Na).
MS: m/z = 138 (M+).
(S)-2,3-Dihydro-1H-inden-1-ol (2i)
[a]D25 +15.7 (c 1.0, CHCl3).
IR (neat): 3271, 2927, 1480, 1341, 1197, 1035, 738 cm–1.
(S)-1-(4-Chlorophenyl)ethanol (2c)
[a]D25 –17.2 (c 1.0, CHCl3).
IR (neat): 3349, 2975, 2926, 1574, 1431, 1201, 1076, 786, 697 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.86 (d, J = 8.0 Hz, 2 H), 7.21 (d,
J = 8.0 Hz, 2 H), 4.87 (q, J = 6.6 Hz, 1 H), 1.46 (d, J = 6.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 25.0, 69.5, 123.4, 125.5, 127.3,
1H NMR (200 MHz, CDCl3): d = 7.36–7.26 (m, 1 H), 7.23–7.12 (m,
3 H), 5.10 (dd, J = 11.7, 5.8 Hz, 1 H), 3.17 (br s, 1 H, OH), 2.98–
2.87 (dd, J = 3.6, 2.2 Hz, 1 H), 2.79–2.62 (dd, J = 7.3, 7.3 Hz, 1 H),
2.43–2.25 (m, 1 H), 1.91–1.74 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 29.6, 35.5, 75.9, 124.1, 124.6,
126.4, 127.9, 143.0, 144.8.
129.6, 134.1, 147.7.
MS: m/z = 156 (M+).
MS: m/z = 157 (M+ + Na).
(S)-1,2,3,4-Tetrahydronaphthalen-1-ol (2j)
[a]D25 +21.4 (c 1.0, CHCl3).
IR (neat): 3435, 2924, 2853, 1458, 1260, 1090, 1027, 801, 738 cm–1.
(S)-1-(4-Methoxyphenyl)ethanol (2d)
[a]D25 –23.2 (c 1.0, CHCl3).
IR (neat): 3411, 2925, 2854, 1512, 1245, 1176, 1034, 832, 760 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.35 (t, J = 8.5 Hz, 1 H), 7.15–7.05
(m, 2 H), 7.05 (t, J = 8.5 Hz, 1 H), 4.68 (dd, J = 4.5, 8.3 Hz, 1 H),
2.90–2.60 (m, 2 H), 2.15–1.60 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 158, 156, 149, 147, 146, 87, 80, 52,
49, 38.
1H NMR (300 MHz, CDCl3): d = 7.25 (d, J = 8.6 Hz, 2 H), 6.80 (d,
J = 8.6 Hz, 2 H), 4.80 (q, J = 6.4 Hz, 1 H), 3.77 (s, 3 H), 1.95 (br s,
1 H, OH), 1.45 (d, J = 6.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 137, 126, 113, 69, 55, 24.
MS: m/z = 151 (M – H+).
MS: m/z = 149 (M + H+).
(S)-1-(4-Nitrophenyl)ethanol (2e)
[a]D25 –27.7 (c 1.0, CHCl3).
Synthesis 2009, No. 11, 1881–1885 © Thieme Stuttgart · New York

PAPER
Enantioselective Reduction of Prochiral Ketones with a Biocatalyst
1885
(R)-Nonan-2-ol (2k)
Acknowledgment
[a]D25 = 12.8 (c 1.0, CHCl3).
Ch.S. thanks Director of IICT for financial assistance.
IR (neat): 3451, 2927, 2857, 1163, 770 cm–1.
1H NMR (200 MHz, CDCl3): d = 3.76 (m, 1 H), 1.47–1.21 (m, 15
H), 0.88 (d, J = 7.3 Hz, 3 H).
References
13C NMR (75 MHz, CDCl3): d = 13.8, 22.5, 23.1, 29.1, 29.5, 31.7,
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39.1, 60.2, 67.7.
MS: m/z = 167 (M+ + Na).
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(2S,4S)-2-(4-Chlorophenyl)tetrahydro-2H-pyran-4-ol (3l)
[a]D25 –21.4, (c 1.0, CHCl3).
IR (neat): 3380, 2952, 2921, 2858, 1515, 1448, 1371, 1284, 1125,
1068, 1044, 985, 813 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.28 (d, J = 8.2 Hz, 2 H), 7.23 (d,
J = 8.2 Hz, 2 H), 4.24 (dd, J = 2.2, 11.7 Hz, 1 H), 4.14 (dd, J = 4.4,
11.7 Hz, 1 H), 3.87–3.78 (m, 1 H), 3.50 (td, J = 4.4, 12.4, 24.2 Hz,
1 H), 2.12 (m, 1 H), 2.05–1.89 (m, 2 H), 1.68–1.45 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 32.8, 40.6, 62.8, 64.2, 73.8, 125.8,
127.3, 128.3, 142.6.
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[a]D25 +15.7 (c 1.0, CHCl3).
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IR (neat): 3382, 2940, 2842, 1489, 1448, 1409, 1364, 1301, 1249,
1163, 1142, 1085, 1050, 987, 691, 885, 823, 717, 689, 594 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.29 (d, J = 8.2 Hz, 2 H), 7.23 (d,
J = 8.2 Hz, 2 H), 4.72 (dd, J = 3.9, 10.4 Hz, 1 H), 4.34–4.22 (m, 1
H), 4.02 (td, J = 2.6, 11.7, 23.4 Hz, 1 H), 3.89 (td, J = 2.6, 11.7, 23.4
Hz, 1 H), 2.11–1.48 (m, 5 H).
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13C NMR (75 MHz, CDCl3): d = 32.8, 40.6, 62.8, 64.2, 73.8, 125.8,
127.3, 128.3, 142.6.
MS: m/z = 213 (M+ + H).
(2S,4S)-2-(Naphthalen-2-yl)tetrahydro-2H-pyran-4-ol (3m)
[a]D25 –21.2 (c 1.0, CHCl3).
IR (neat): 3433, 3028, 2908, 2842, 1457, 1342, 1208, 1081, 1012,
812, 748, 698, 477 cm–1.
1H NMR (200 MHz, CDCl3): d = 8.04 (d, J = 9.2 Hz, 1 H), 7.80 (dd,
J = 1.8, 7.1 Hz, 1 H), 7.71 (d, J = 8.3 Hz, 1 H), 7.60 (d, J = 6.4 Hz,
1 H), 7.50–7.37 (m, 3 H), 5.54 (dd, J = 1.8, 11.5 Hz, 1 H), 4.37 (m,
1 H), 4.20 (td, J = 2.2, 11.7, 24.3 Hz, 1 H), 4.02 (dd, J = 5.6, 12.0
Hz, 1 H), 2.23–1.98 (m, 2 H), 1.91 (td, J = 2.6, 11.5 Hz, 1 H), 1.75–
1.63 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 35.6, 42.2, 66.5, 68.5, 75.3, 123.0,
123.1, 125.42, 125.46, 125.9, 128.1, 128.8, 130.3, 133.7, 137.2.
MS: m/z = 252 (M+ + H + Na).
(f) Maczka, W. K.; Mironowicz, A. Tetrahedron:
Asymmetry 2002, 13, 2299.
(10) Kumaraswamy, G.; Ramesh, S. Green Chem. 2003, 5, 306.
(11) (a) Haslegrave, J. A.; Jones, J. B. J. Am. Chem. Soc. 1982,
104, 4667. (b) Harada, T.; Kurokawa, H.; Kagamihara, Y.;
Tanaka, S.; Inoue, A.; Oku, A. J. Org. Chem. 1992, 57,
1412. (c) Nunez, M. T.; Martin, V. S. J. Org. Chem. 1990,
55, 1928. (d) Yadav, J. S.; Reddy, B. V. S.; Padmavani, B.;
Venugopal, Ch.; Rao, A. B. Tetrahedron Lett. 2007, 48,
4613. (e) Yadav, J. S.; Reddy, B. V. S.; Sreelakshmi, Ch.;
Narayana Kumar, G. G. K. S.; Rao, A. B. Tetrahedron Lett.
2008, 49, 2768.
(2R,4S)-2-(Naphthalen-2-yl)tetrahydro-2H-pyran-4-ol (4m)
[a]D25 +18.6 (c 1.0, CHCl3).
IR (neat): 3428, 3056, 2923, 2850, 1465, 1361, 1245, 1081, 819,
748, 477 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.96 (d, J = 3.4 Hz, 1 H), 7.78 (dd,
J = 15.6, 7.8 Hz, 2 H), 7.60 (d, J = 6.5 Hz, 1 H), 7.54–7.37 (m, 3 H),
4.98 (d, J = 11.7 Hz, 1 H), 4.25 (dd, J = 11.7, 3.9 Hz, 1 H), 4.11–
3.91 (m, 1 H), 3.69 (td, J = 13.0, 2.6 Hz, 1 H), 2.36 (dt, J = 13.0, 2.6
Hz, 1 H), 2.12–1.92 (m, 2 H), 1.76–1.53 (m, 3 H).
(12) Prelog, V. Pure Appl. Chem. 1964, 9, 119.
13C NMR (75 MHz, CDCl3): d = 35.1, 42.9, 66.1, 67.8, 78.1, 122.3,
123.9, 124.2, 125.5, 125.7, 126.7, 127.3, 127.7, 129.2, 134.3.
MS: m/z = 252 (M+ + H + Na).
Synthesis 2009, No. 11, 1881–1885 © Thieme Stuttgart · New York