Stereoselective total synthesis of botryolide e

Article abstract of DOI:10.1002/hlca.201100512

The stereoselective total synthesis of the naturally occurring γ-lactone derivative botryolide E (1) was accomplished with acetaldehyde as the starting material (Scheme 2). The asymmetric allyl boration, asymmetric dihydroxylation, chelation-mediated dias

Full text of DOI:10.1002/hlca.201100512

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Helvetica Chimica Acta – Vol. 95 (2012)
Stereoselective Total Synthesis of Botryolide E1)
by Boyapati Veeranjaneyulu, Malampati Srilatha, Gandolla Chinna Reddy, and Biswanath Das*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500007, India
(phone: þ 91-40-7193434; fax: þ 91-40-7160512; e-mail: biswanathdas@yahoo.com)
The stereoselective total synthesis of the naturally occurring g-lactone derivative botryolide E (1)
was accomplished with acetaldehyde as the starting material (Scheme 2). The asymmetric allyl boration,
asymmetric dihydroxylation, chelation-mediated diastereoselective vinylation, and ring-closing meta-
thesis reaction are the key steps. The method can conveniently be utilized for the preparation of other
related g-lactone derivatives.
Introduction. – The g-lactone (butenolide) moiety is an integral structural
component of an ever increasing number of biologically active natural products [1].
These compounds exhibit a wide range of biological activities including cytotoxic [2],
antibacterial [3], antifungal [3], cyclooxygenase [4], and antiproliferative properties
[5]. Botryolide E (¼(5S)-5-[(1S,3R)-3-(acetyloxy)-1-hydroxybutyl]furan-2(5H)-one;
1), a member of this group, was isolated from cultures of a fungicolous isolate of
Botryotrichum sp. (NRRL 38180) along with other botryolides [6]. The biological
activities of this compound have not been completely studied but recently it was found
to possess antibacterial and antifungal activities [3]. The structure of 1 was confirmed
by its NMR and MS data [6]. The absolute configuration of 1 was confirmed by its first
stereoselective synthesis [3]. Later, so far, no other asymmetric synthesis of botryolide
E (1) has been reported. In continuation of our work [7] on the synthesis of bioactive
natural products, we have taken up the asymmetric synthesis of 1 which we describe
here.
Results and Discussion. – The retrosynthetic analysis of botryolide E (1) is
summarized in Scheme 1. The disconnection process began with the C(2)¼C(3) bond,
which could be realized by ring-closing metathesis. This led to the key intermediate 2a
Scheme 1. Retrosynthetic Pathway to Botryolide E (1)
1
)
Part 55 in the series, ꢂSynthetic Studies on Natural Productsꢃ.
ꢀ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 95 (2012)
1153
which could be prepared by chelation-mediated syn-selective vinylation of the
aldehyde obtained by oxidation of the primary alcohol 3. Compound 3 could be
obtained by a Sharpless asymmetric dihydroxylation reaction of 4, generated by
asymmetric allylation of acetaldehyde (5).
The synthesis of 1 started from freshly distilled acetaldehyde (5; Scheme 2) to
produce (2R)-pent-4-en-2-ol (6) with high enantioselectivity by following the literature
procedure [8]. The OH group of 6 was acetylated with Ac2O and Et3N to give ester 4.
Asymmetric dihydroxylation of compound 4 by the Sharpless protocol [9] yielded diol 7
with high diastereoselectivity. The primary OH function of the latter was protected as
its corresponding (tert-butyl)dimethylsilyl (tBuMe2Si) ether 8 with tBuMe2SiCl and 1H-
t
imidazole. Next, the protection of the secondary OH function in 8 with BuMe2SiCl,
1H-imidazole, and catalytic amounts of N,N-dimethylpyridin-4-amine (DMAP)
t
produced compound 9. Selective deprotection of the BuMe2Si ether in 9 with
pyridinium p-toluenesulfonate (¼ pyridinium 4-methylbenzenesulfonate; PPTS) in
MeOH afforded the primary alcohol 3 [10]. Initially this deprotection failed by carrying
out the reaction in MeOH with p-toluenesulfonic acid (TsOH) which led to a mixture
of products with complete consumption of the starting material. Attempts to oxidize
alcohol 3 to the corresponding aldehyde with 2-iodoxybenzoic acid (IBX) or
pyridinium dichromate (PDC) were not successful and led to a mixture of compounds
along with the starting material. Later the oxidation was successful with pyridinium
Scheme 2. Synthesis of Botryolide E (1). TBDMS ¼ tBuMe2Si, TBDPS ¼ tBuPh2Si.
a) Ac2O, Et3N, CH2Cl2, 08 – r.t., 4 h; 91%. b) K3[Fe(CN)6], K2CO3, K2OsO4 · 2 H2O, (DHQD)2PHAL
(Aldrich), tBuOH/H2O (1:1), 08, 8 h; 83%. c) tBuMe2SiCl, 1H-imidazole, CH2Cl2, 08 – r.t., 3 h; 81%. d)
tBuPh2SiCl, 1H-imidazole, cat. DMAP, CH2Cl2, 08 – r.t., 8 h; 87%. e) PPTS, MeOH, r.t, 12 h; 79%. f) 1.
PCC, CH2Cl2, r.t., 5 h; 84%; 2. CH2¼CHMgBr, MgBr2 · Et2O, CH2Cl2, ꢀ 788, 12 h; 61%. g)
i
CH2¼CHCOCl, Pr2NEt, CH2Cl2, 08, 5 h; 84%. h) Catalyst G (5 mol-%), CH2Cl2, reflux, 6 h; 69%. i)
Bu4NþFꢀ, THF, 08, 1 h; 64%.

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Helvetica Chimica Acta – Vol. 95 (2012)
chlorochromate (PCC) to afford aldehyde 3a (Table). The latter was subjected to
chelation-mediated selective vinylation under different conditions; the best result was
achieved with vinyl magnesium bromide (H2C¼CHMgBr) and MgBr2 · Et2O in CH2Cl2
at ꢀ 788 which yielded a mixture of syn- and anti-diastereoisomers 2a and 2b in the
ratio of 95 :5 (Table) [11]. The compounds 2a and 2b were separated by column
chromatography. Acrylation of 2a with acryloyl chloride (¼ prop-2-enoyl chloride) and
diisopropylethylamine (Pr2NEt) afforded 10, which underwent a ring-closing meta-
thesis reaction induced by Grubbsꢃ 1st-generation catalyst G [12] to yield the
t
unsaturated g-lactone 11. Selective deprotection of the BuMe2Si group of 11 with
Bu4NF in THF led to botryolide E (1), the spectroscopic data of which were identical to
those of natural 1 [3][6].
Table. Metal-Catalyzed Diastereoselective Vinylation
Conditionsa)
Yield [%]b)
syn/anti (2a/2b)c)
CH2¼CHMgBr, MgBr2 · Et2O, dry THF, ꢀ 788, 5 h
CH2¼CHMgBr, MgBr2 · Et2O, dry Et2O, ꢀ 788, 5 h
CH2¼CHMgBr, MgBr2 · Et2O, dry CH2Cl2, ꢀ 788, 12 h
CH2¼CHMgBr, MgBr2 · Et2O, dry CH2Cl2, ꢀ 208, 12 h
CH2¼CHMgBr, dry Et2O, 08, 4 h
81
77
61
67
89
60 : 40
67: 33
95 : 5
80 : 20
55 : 45d)
a) Reaction conditions: aldehyde 3a (1.0 equiv.), CH2¼CHMgBr (2.5 equiv.), and MgBr2 · Et2O (1.2
c
equiv). b) Yield of isolated products after column chromotography. ) The ratio syn/anti was determined
from the mixture. d) The reaction was carried out without catalyst.
In conclusion, the stereoselective synthesis of botryolide E was successfully
accomplished by means of an asymmetric allyl boration [8], an asymmetric
dihydroxylation, a chelation-mediated diastereoselective vinylation, and a ring-closing
metathesis reaction as the key steps. This method can conveniently be utilized for the
preparation of other related g-lactone derivatives.
The authors thank UGC and CSIR, New Delhi, for financial assistance.
Experimental Part
General. All commercially available reagents were used directly without further purification unless
otherwise stated. The solvents used were all of AR grade and were distilled under a positive pressure of
dry N2 where necessary. All reactions were performed in a pre-dried apparatus unless otherwise stated.
Yields were those of purified compounds unless otherwise stated. Column chromatography (CC): silica
gel (SiO2; 60 – 120 mesh; Qingdao Marine Chemical, P. R. China); FC ¼ flash chromatography. TLC:
SiO2 60 F254 plates (Merck). Optical rotations: Jasco-DIP-300 digital polarimeter. IR Spectra:
PerkinꢀElmer-RX1 FT-IR spectrophotometer; n in cmꢀ1. NMR Spectra: Gemini 200 MHz spectrometer;

Helvetica Chimica Acta – Vol. 95 (2012)
1155
in CDCl3; d in ppm rel. to Me4Si as internal standard, J in Hz. ESI-MS: VG-Autospec micromass; in m/z.
HR-MS: QSTAR XL, hybrid MS system (Applied Biosystems); in m/z.
(2R)-Pent-4-en-2-yl Acetate (¼(2R)-Pent-4-en-2-ol Acetate; 4). To a soln. of (2R)-pent-4-en-2-ol (6;
4.0 g, 46.51 mmol) in dry CH2Cl2 (50 ml) at 08, Et3N (12.96 ml, 93.02 mmol) and a cat. amounts of DMAP
were added. The mixture was stirred for 15 min, then Ac2O (14.23 g, 13.15 ml) was slowly added, and the
mixture warmed to r.t. After stirring for 4 h, the mixture was diluted with CH2Cl2 (10 ml) and the reaction
quenched by slow addition of H2O (20 ml). The org. layer was washed with brine (2 ꢁ 30 ml), dried (anh.
Na2SO4), and concentrated, and the residue purified by CC (AcOEt/hexane 2 :8): pure 4 (5.41 g, 91%).
IR: 1733, 1637, 1239, 1108. 1H-NMR (200 MHz): 5.76 – 5.63 (m, 1 H); 5.06 – 5.04 (m, 2 H); 4.92 – 4.85 (m,
1 H); 1.98 (s, 3 H); 1.85 – 1.77 (m, 2 H); 1.28 (d, J ¼ 6.0, 3 H). 13C-NMR (50 MHz): 176.2; 133.6; 117.6;
69.7; 40.3; 20.8; 19.5. Anal. calc. for C7H12O2 (128.17): C 65.60, H 9.44; found: C 65.56, H 9.49.
(2R,4S)-4,5-Dihydroxypentan-2-yl Acetate ( ¼ (2S,4R)-Pentane-1,2,4-triol 4-Acetate; 7). To a stirred
suspension of K3[Fe(CN)]6 (40.1g, 121.8 mmol), K2CO3 (16.8 g, 121.8 mmol), K2OsO4 · 2 H2O (0.019 g,
0.052 mmol) and 1,4-bis(9-O-dihydroquinidinyl)phthalazine (¼(9S,9’’S)-9,9’’-[phthalazine-1,4-diylbis-
(oxy)]bis[10,11-dihydro-6’-methoxycinchonane]; (DHQD)2PHAL; 0.079 g, 0.101 mmol) in tBuOH/H2O
1:1 (500 ml) at 08, a soln. of 6 (5.2 g, 40.62 mmol) in tBuOH (5 ml) was added slowly within 30 min. The
mixture was stirred for 8 h at 08. After completion of the reaction, the mixture was quenched with Na2SO3
and stirred for another 20 min. The mixture was filtered over a Celite pad. The residue thus obtained was
washed with hot AcOEt. The org. layer from the filtrate was separated, and the aq. layer thus obtained
was extracted with AcOEt (2 ꢁ 400 ml). The combined org. layers were washed with brine (300 ml),
dried (anh. Na2SO4), and concentrated. The residue was purified by CC (AcOEt/hexane 5 :5): pure 7
(5.46 g, 83%). [a]D25 ¼ ꢀ2.3 (c ¼ 1.0, CHCl3). IR: 3430, 2928, 1713, 1634, 1253, 1165. 1H-NMR (200 MHz):
5.11 – 5.05 (m, 1 H); 3.58 – 3.48 (m, 2 H); 3.37 – 3.32 (m, 1 H); 2.02 (s, 3 H); 1.56 – 1.51 (m, 2 H); 1.24 (d,
J ¼ 6.0, 3 H). 13C-NMR (50 MHz): 171.4; 68.3; 68.0; 66.4; 39.9; 21.2; 20.8. Anal. calc. for C7H14O4: C
51.84, H 8.70; found: C 51.73, H 8.77.
(2R,4S)-5-{[(tert-Butyl)dimethylsilyl]oxy}-4-hydroxypentan-2-yl Acetate (¼(2R,4S)-5-{[(tert-Bu-
tyl)dimethylsilyl]oxy}pentane-2,4-diol 2-Acetate; 8). To a stirred soln. of 7 (5.2 g, 32.09 mmol) in dry
CH2Cl2 (70 ml) were added 1H-imidazole (2.4 g, 35.3 mmol) and tBuMe2SiCl (5.31 g, 35.3 mmol) at 08.
The mixture was allowed to reach r.t. and then stirred for 3 h. After diluation with CH2Cl2 (15 ml), the
org. layer was washed with brine (50 ml), dried (Na2SO4), and concentrated, and the residue subjected to
CC (AcOEt/hexane 2 :8): 8 (7.16 g, 81%). [a]D25 ¼ ꢀ10.2 (c ¼ 0.95, CHCl3). IR: 3458, 2955, 2857, 1738,
1
1465, 1373, 1254, 1097. H-NMR (200 MHz): 5.14 – 5.02 (m, 1 H); 3.60 – 3.51 (m, 2 H); 3.45 – 3.38 (m,
1 H); 2.58 (br. s, 1 H); 2.02 (s, 3 H); 1.65 – 1.45 (m, 2 H); 1.26 (d, J ¼ 6.4, 3 H); 0.89 (s, 9 H); 0.05 (s, 6 H).
13C-NMR (50 MHz): 170.3; 68.3; 68.1; 67.4; 39.9; 26.0; 21.2; 20.9; 18.4; ꢀ 5.1. ESI-MS: 294 ([M þ 18]þ).
(2R,4S)-5-{[(tert-Butyl)dimethylsilyl]oxy}-4-{[(tert-butyl)diphenylsilyl]oxy}pentan-2-yl Acetate
(¼(2R,4S)-5-{[(tert-Butyl)dimethylsilyl]oxy}-4-{[(tert-butyl)diphenylsilyl]oxy}pentan-2-ol Acetate; 9).
To a stirred soln. of 8 (7.0 g, 25.36 mmol) in dry CH2Cl2 (90 ml) were added 1H-imidazole (2.58 g,
38.04 mmol) and a cat. amount of DMAP at 08 and stirred for 20 min. tBuPh2SiCl (9.73 ml, 38.04 mmol)
was added to this at 08. The mixture was warmed to r.t., stirred for 8 h, and then diluted with CH2Cl2
(25 ml). The org. layer was washed with brine (70 ml), dried (Na2SO4), and concentrated, and the
residue subjected to CC (AcOEt/hexane 1:9): 9 (11.31 g, 87%). [a]3D4 ¼ ꢀ13.9 (c ¼ 1.9, CHCl3); IR: 2955,
2857, 1738, 1466, 1369, 1245, 1108. 1H-NMR (200 MHz): 7.66 – 7.64 (m, 4 H); 7.40 – 7.32 (m, 6 H); 5.04 –
5.01 (m, 1 H); 3.71 – 3.66 (m, 1 H); 3.43 – 3.37 (m, 2 H); 1.90 – 1.86 (m, 1 H); 1.84 (s, 3 H); 1.64 – 1.59 (m,
1 H); 1.16 (d, J ¼ 5.9, 3 H); 1.04 (s, 9 H); 0.81 (s, 9 H); ꢀ 0.09 (s, 3 H); ꢀ 0.15 (s, 3 H). 13C-NMR
(50 MHz): 170.1; 136.0; 135.8; 134.6; 133.6; 129.7; 129.5; 127.7; 127.4; 70.9; 68.1; 66.8; 41.1; 27.1; 25.9; 21.2;
20.8; 19.4; 18.3; ꢀ 5.4. ESI-MS: 537 ([M þ Na]þ).
(2R,4S)-4-{[(tert-Butyl)diphenylsilyl]oxy}-5-hydroxypentan-2-yl Acetate (¼(2S,4R)-2-{[(tert-Bu-
tyl)diphenylsilyl]oxy}pentane-1,4-diol 4-Acetate; 3). To a stirred soln. of 9 (7.2 g, 13.98 mmol) in anh.
MeOH at 08 was added PPTS (0.702 g, 2.79 mmol). Then the mixture was warmed to r.t. and stirred for
12 h. After completion of the reaction, the mixture was concentrated and the residue purified by CC
(AcOEt/hexane 3 :7): pure 3 (4.41 g, 79%). [a]3D4 ¼ ꢀ2.9 (c ¼ 1.9, CHCl3). IR: 3489, 3071, 2931, 2858,
1
1735, 1247, 1110. H-NMR (200 MHz): 7.66 – 7.60 (m, 4 H); 7.38 – 7.34 (m, 6 H); 4.88 – 4.78 (m, 1 H);
3.77 – 3.71 (m, 1 H); 3.49 – 3.44 (m, 2 H); 1.81 (s, 3 H); 1.76 – 1.59 (m, 2 H); 1.07 (d, J ¼ 6.0, 3 H); 1.06 (s,

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Helvetica Chimica Acta – Vol. 95 (2012)
9 H). 13C-NMR (50 MHz): 170.3; 135.9; 135.5; 134.0; 133.0; 129.8; 127.7; 71.3; 68.2; 66.6; 40.3; 26.9; 21.2;
20.3; 19.2. ESI-MS: 423 ([M þ Na]þ).
(2R,4S,5S)-4-{[(tert-Butyl)diphenylsilyl]oxy}-5-hydroxyhept-6-en-2-yl Acetate (¼(2R,4S,5S)-4-
{[(tert-Butyl)diphenylsilyl}oxy}hept-6-ene-2,5-diol 2-Acetate; 2a). To a soln. of 3 (2.1 g, 5.25 mmol) in
dry CH2Cl2 (30 ml) at r.t., Celite (1.0 g) and PCC (1.69 g, 7.87 mmol) were added while stirring. After 5 h
stirring, the mixture was diluted with CH2Cl2 (10 ml) and filtered over a Celite pad. The residue thus
obtained was washed with CH2Cl2. The combined org. layers were washed with brine, dried (Na2SO4),
and concentrated, and the residue was purified by FC: aldehyde 3a (1.74 g, 84%) which was used
immediately for the next step.
To a soln. of 3a (1.74 g, 4.37 mmol) in dry CH2Cl2 (50 ml), MgBr2 · E2O (1.35 g, 5.24 mmol) was
added while stirring. The soln. was stirred well for 1 h and cooled to ꢀ 788. A soln. of 1m CH2¼CHMgBr
in THF (10.9 ml, 10.9 mmol) was added slowly within 15 min. The mixture was stirred for 12 h and then
allowed to reach r.t. The reaction was quenched with sat. NH4Cl soln. (10 ml) and H2O (20 ml), the aq.
layer washed with CH2Cl2 (2 ꢁ 50 ml), the combined org. layer dried (Na2SO4) and concentrated, and the
residue purified by CC (AcOEt/hexane 2 :8): 2a/2b 95 :5; 0.55 g of 2a was isolated in 93% yield. [a]D34
¼
ꢀ1.6 (c ¼ 2.3, CHCl3). IR: 3452, 3071, 2931, 2857, 1735, 1634, 1241, 1104. 1H-NMR (200 MHz): 7.66 – 7.60
(m, 4 H); 7.41 – 7.32 (m, 6 H); 5.94 – 5.83 (m, 1 H); 5.31 – 5.16 (m, 2 H); 4.71 – 4.62 (m, 1 H); 4.03 – 3.99
(m, 1 H); 3.67 (m, 1 H); 2.03 (br. s, 1 H); 1.78 (s, 3 H); 1.49 – 1.41 (m, 2 H); 1.04 (s, 9 H); 0.94 (d, J ¼ 6.0,
3 H). 13C-NMR (50 MHz): 170.2; 135.9; 135.7; 133.9; 133.0; 129.8; 127.7; 116.5; 75.6; 73.5; 68.3; 38.0; 27.0;
21.1; 20.4; 19.3. ESI-MS: 449 ([M þ Na]þ).
(3S,4S,6R)-6-(Acetyloxy)-4-{[(tert-butyl)diphenylsilyl]oxy}hept-1-en-3-yl Acrylate (¼(1S,2S,4R)-4-
(Acetyloxy)-4-(tert-butyldiphenylsilyl]oxy}-1-ethenylpentyl Prob-2-enoate; 10). To a stirred soln. of 2a
i
(0.8 g, 1.87 mmol) in dry CH2Cl2 (8 ml) under N2 atmosphere at 08 were added Pr2NEt (1.62 ml,
9.35 mmol) and acryloyl chloride (0.45 ml, 5.61 mmol), and the mixture was stirred for 5 h and then
diluted with CH2Cl2 (10 ml). The org. layer was washed with NaHCO3 (10 ml), dried (anh. Na2SO4), and
concentrated and the residue subjected to CC (AcOEt/hexane 2 :8): 10 (0.75 g, 84%). [a]2D9 ¼ þ7.5 (c ¼
1.5, CHCl3). IR: 3065, 2928, 2854, 1735, 1724, 1637, 1239, 1104. 1H-NMR (200 MHz): 7.70 – 7.66 (m, 4 H);
7.42 – 7.34 (m, 6 H); 6.31 (dd, J ¼ 1.5, 17.2, 1 H); 5.98 – 5.82 (m, 2 H); 5.71 (dd, J ¼ 1.5, 10.5, 1 H); 5.32 –
5.18 (m, 3 H); 4.83 – 4.72 (m, 1 H); 3.89 – 3.75 (m, 1 H); 1.78 (s, 3 H); 1.59 – 1.48 (m, 2 H); 1.07 – 1.04 (m,
2 H). 13C-NMR (50 MHz): 170.1; 164.5; 136.0; 135.8; 133.6; 133.2; 132.4; 130.4; 128.3; 127.7; 127.6; 118.4;
76.3; 70.8; 68.0; 39.7; 27.1; 21.1; 20.4; 19.5. ESI-MS: 503 ([M þ Na]þ).
(2R,4S)-4-{[(tert-Butyl)diphenylsilyl]oxy}-4-[(2S)-2,5-dihydro-5-oxo-furan-2-yl)butan-2-yl Acetate
( ¼ (5S)-5-{(1S,3R)-3-(Acetyloxy)-1-{[(tert-butyl)diphenylsilyl]oxy}butyl}furan-2(5H)-one; 11). A soln.
of 10 (0.25 g, 0.52 mmol) in dry CH2Cl2 (180 ml) was first flushed by bubbling with an N2 flow, after which
Grubbsꢀ 1st-generation catalyst G (0.021 g, 0.026 mmol) was added at once, and the resulting mixture was
heated under N2 at 508 for 6 h. After cooling, the solvent was evaporated and the residue purified by CC
(AcOEt/hexane 2 :8): pure 11 (0.16 g, 69%). [a]2D5 ¼ ꢀ24.3 (c ¼ 0.2, CHCl3). 1H-NMR (200 MHz): 7.70 –
7.66 (m, 4 H); 7.44 (dd, J ¼ 5.9, 1.6, 1 H); 7.42 – 7.34 (m, 6 H); 6.21 (dd, J ¼ 5.9, 1.6, 1 H); 5.16 – 5.03 (m,
2 H); 3.91 – 3.86 (m, 1 H); 1.98 (s, 1 H); 1.84 – 1.73 (m, 2 H); 1.15 (d, J ¼ 6.0, 2 H); 1.05 (s, 9 H). 13C-NMR
(50 MHz): 172.3; 171.9; 152.8; 136.0; 135.7; 132.6; 132.2; 127.6; 127.5; 120.4; 84.5; 68.0; 67.9; 38.7; 27.0;
21.0; 20.4; 19.4. ESI-MS: 475 ([M þ Na]þ).
(2R,4S)-4-Hydroxy-4-[(2S)-2,5-dihydro-5-oxo-furan-2-yl]butan-2-yl Acetate (¼ Botryolide E ¼ (5S)-
5-[(1S,3R)-3-(Acetyloxy)-1-hydroxybutyl]furan-2(5H)-one; 1). To a soln. of 10 (0.12 g, 0.265 mmol) in
dry THF (4 ml), 1m Bu4N in THF (0.52 ml, 0.52 mmol) at 08 was added dropwise. The mixture was stirred
at 08 for 1 h. After completion of the reaction, the mixture was diluted with AcOEt (10 ml), the org. layer
washed with brine (2 ꢁ 8 ml), dried (Na2SO4), and concentrated, and the residue subjected to CC
(AcOEt/hexane 3 :7): pure 1 (0.036 g, 64%). [a]2D5 ¼ ꢀ36.4 (c ¼ 0.05, CHCl3). 1H-NMR (200 MHz): 7.46
(dd, J ¼ 6.0, 1.8, 1 H); 6.17 (dd, J ¼ 6.0, 1.8, 1 H); 5.14 – 5.08 (m, 1 H); 5.04 – 5.01 (m, 1 H); 3.89 – 3.85 (m,
1 H); 2.01 (s, 1 H); 1.81 – 1.70 (m, 2 H); 1.26 (d, J ¼ 6.0, 3 H). 13C-NMR (50 MHz): 172.8; 171.9; 153.2;
123.0; 85.1; 67.6; 67.4; 39.1; 21.1; 20.6. ESI-MS: 237 ([M þ Na]þ).

Helvetica Chimica Acta – Vol. 95 (2012)
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Received December 20, 2011