Stereoselective synthesis of umuravumbolide

Article abstract of DOI:10.1016/j.tetasy.2013.04.004

An efficient stereoselective total synthesis of umuravumbolide has been developed. The key features of the synthesis include Jacobsen resolution, Wadsworth Emmons olefination and silyl-tethered ring closing metathesis.

Full text of DOI:10.1016/j.tetasy.2013.04.004

Tetrahedron: Asymmetry 24 (2013) 594–598
Contents lists available at SciVerse ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective synthesis of umuravumbolide
⇑
⇑
T. Vijaya Kumar, G. Venkateswar Reddy, K. Suresh Babu , J. Madhusudana Rao
Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 March 2013
Accepted 8 April 2013
An efficient stereoselective total synthesis of umuravumbolide has been developed. The key features of
the synthesis include Jacobsen resolution, Wadsworth Emmons olefination and silyl-tethered ring closing
metathesis.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
1a and 1b involving a Noyori asymmetric reduction and Still–
Gennari olefination as key steps6b while the other approaches
Desacetylumuravumbolide 1a and umuravumbolide 1b were
first isolated by Van Puyvelde et al. in 1979 from Tetradenia riparia
(Iboza riparia) of Lamiaceae family found in central Africa.1 Extracts
made from this plant are used in traditional medicine as a remedy
for malaria, diarrhoea and for several types of fevers and aches.2
Later, Davies-Coleman and Rivett determined the absolute config-
uration of 1a and 1b based on NMR and CD spectroscopic studies
and also reported the specific rotation of these compounds.3
Structurally, these natural products belong to the 6-substituted
have exploited Crimmins aldol,6c and Jacobsen’s resolution.6d In a
continuation of our research program directed towards the
synthesis of biologically active natural lactones,7 we herein report
a novel strategy for the synthesis of 1a and 1b, which is different
from the previously reported syntheses for the installation of the
Z-olefin, relying on a silyl-tethered ring closing metathesis.
2. Results and discussion
5,6-dihydro-
a-pyrone family, which contains an electrophilic
In our synthetic plan, the target molecule was planned from
intermediate 2 via ring closing metathesis followed by acid
promoted deprotection and lactonization, which in turn, could be
obtained from secondary allylic alcohol fragments 3 and 4 through
silyl protection followed by Z-selective Wittig olefination. Frag-
ments 3 and 4 would be constructed from 5 and 6, respectively
(see Scheme 1).
The synthesis of umuravumbolide started from commercially
available 1,2-epoxy hexane 5, which was subjected to solvent-free
hydrolytic kinetic resolution with (acetao)(aqua)(S,S)-N,N0bis(3,5-
di-tert-butylsalicylidene-1,2-cyclohexanediamino)cobalt(III) to af-
ford the required chiral epoxide 7 in 42% yield.8 The regioselective
ring opening of epoxide 7 with dimethylsulfonium methylide
(Me3S+Iꢀ, n-BuLi) afforded the required allylic alcohol 3 in 90%
yield and with 96% enantioselectivity (Scheme 2).9 The enantiopu-
rity was determined by chiral HPLC and the absolute configuration
was assigned by comparing the specific rotation data with that
reported in the literature.10 With the required fragment 3 in hand,
we began the synthesis of the other key fragment 4 with enantio-
merically pure (S)-2-(2-(4-methoxybenzyloxy)ethyl)oxirane 8,
a,b-unsaturated-d-lactone ring attached to a side chain with a Z-
olefin at the C7–C8 position and hydroxy or acetyl functional
groups at C9 (Fig. 1). This class of natural products displays a wide
range of biological properties such as antimicrobial, antifungal and
phytotoxic activities, as well as cytotoxicity against human tumour
cells.4 Their promising biological profiles as well as interesting
structures have attracted significant attention from a number of
synthetic chemists.5
O
O
1
O
3
4
2
OH
OAc
O
9
6
7
8
5
1a
1b
Figure 1. Structures of desacetylumuravumbolide 1a and umuravumbolide 1b.
To date, four total syntheses have been reported for 1a and 1b
in the literature. In an early synthesis reported by Ramachandran
et al., asymmetric reduction, allylboration and ring-closing
metathesis were used as the key steps in the synthesis.6a Recently
Sabitha et al. reported on the synthesis and anti tumour activity of
which was prepared from commercially available L-aspartic acid
using the literature procedure.11 The regioselective ring opening
of epoxide 8 with dimethylsulfonium methylide (Me3S+Iꢀ, n-BuLi)
afforded the required chiral alcohol 4 in 93% yield and with 98% ee
(Scheme 3).9 The enantiopurity was analysed by chiral HPLC and
⇑
Corresponding authors. Tel.: +91 40 27191881; fax: +91 40 27160512.
E-mail address: suresh@iict.res.in (K.S. Babu).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.04.004

T. V. Kumar et al. / Tetrahedron: Asymmetry 24 (2013) 594–598
iPr iPr
595
O
Si
O
O
OR
O
CO2Me
1b
2
OH
OH
O
L-aspartic acid
+
OPMB
5
3
4
6
Scheme 1. Retrosynthetic analysis of umuravumbolide 1b.
OH
O
O
a
b
5
7 (42%)
3 (90%)
96% ee
Scheme 2. Reagents and conditions: (a) (S,S)-(salen)CoIII(OAc), H2O (0.55 equiv), rt, 16 h; (b) (CH3)3S+Iꢀ, n-BuLi, ꢀ20 °C, 2 h.
OH
O
ref. 7
a
L-aspartic acid
PMBO
PMBO
6
8
4
(93%)
98% ee
Scheme 3. Reagents and conditions: (a) (CH3)3S+Iꢀ, n-BuLi, ꢀ20 °C, 2 h.
the absolute configuration was assigned by comparing the specific
rotation data reported in the literature.12
With the two secondary allylic alcohol fragments 3 and 4 in
hand, we then proceeded with the introduction of the C7–C8, Z-ole-
fin via temporary silyl-tethered ring closing metathesis. In order to
construct the RCM precursor 2, allylic alcohol 3 was covalently
tethered to 4 through a diisopropylsilyl linker to give disiloxane 9
in 72% yield and with a 98% diastereomeric ratio.14a Next, the
PMB group was cleaved using DDQ in CH2Cl2/H2O to give alcohol
10 in 85% yield. Subsequent oxidation of the resulting alcohol with
Dess–Martin periodinane gave the corresponding aldehyde, which
was directly submitted to chain elongation employing the Still
iPr
O
iPr
O
OH
OH
Si
a
OPMB
+
OPMB
3
4
9
(72%)
dr = 98:2
iPr
O
iPr
O
iPr
O
iPr
O
Si
Si
c
d
b
OH
CO2Me
10
2
(85%)
(80%, over two
steps, Z:E > 95:5)
O
iPr
O
iPr
O
Si
e
f
O
OAc
O
OH
O
CO2Me
1a
(80%)
1b
(92%)
11
(89%, Z-isomer
exclusively formed)
Scheme 4. Reagents and conditions: (a) iPr2SiCl2, imidazole, CH2Cl2, 0 °C to rt, 4 h; (b) DDQ, CH2Cl2/H2O, 0 °C to rt, 2 h; (c) (i) DMP, NaHCO3, CH2Cl2, 0 °C to rt, 1 h; (ii)
(CF3CH2O)2P(O)CH2COOCH3, NaH, THF, ꢀ78 °C, 1 h; (d) Grubbs-II 9 mol %, 40 °C, CH2Cl2, 2 h; (e) 3 M HCl, THF (1:1), 0 °C to rt, 6 h; (f) Ac2O, Et3N, DMAP, CH2Cl2, 0 °C to rt, 1 h.

596
T. V. Kumar et al. / Tetrahedron: Asymmetry 24 (2013) 594–598
Gennari reagent [(F3CCH2O)2POCH2CO2Me], to afford the corre-
stirred for 1 h at ꢀ20 °C. After being stirred for 1 h, a solution of
epoxide 2 (1 g, 9.98 mmol) in THF (6 mL) was added. The resultant
cloudy suspension was allowed to warm slowly to 25 °C over 1 h
and stirred for another 1 h. After consumption of the starting mate-
rial (monitored by TLC), the reaction mixture was quenched with
water. The layers were separated and the aqueous layer was ex-
tracted twice with EtOAc. The combined organic layers were dried
over Na2SO4 and concentrated under reduced pressure. Purification
by flash chromatography (5% EtOAc/hexanes) gave 1.030 g (90%) of
sponding
a,b-unsaturated ester 2 (Z:E >95:5) in 80% yield (over
two steps).13
Atthisstage, inorder to install C7–C8 olefin with aZ-configuration,
intermediate 2 was subjected to RCM with Grubbs second generation
catalyst (9 mol %, 0.06 M in CH2Cl2) at 40 °C, this led to smooth cycli-
zation to exclusively afford compound 11 in 89% yield.14 One-pot acid
promoted desilylation, followed by concomitant lactonization using
3 M HCl/THF (1:1) gave the required lactone desacetylumuravumbo-
lide 1a in 80% yield. Finally, acetylation of the secondary alcohol affor-
ded umuravumbolide 1b in 92% yield (Scheme 4). The enantiomeric
purity and analytical data (1H NMR, 13C NMR and mass spectra) were
in agreement with those reported for the natural product3
allylic alcohol 12 as a colourless liquid. ½a D20
¼ þ9:3 (c 1.5, CHCl3). IR
ꢁ
(KBr);2923, 2852, 1462, 1219, 772 cmꢀ1; 1HNMR(CDCl3, 300 MHz):
d = 5.81–5.93 (m, 1H), 5.26–5.08 (dd, J = 17.37, 10.57 Hz, 2H), 4.10
(q, J = 6.79 Hz, 1H), 1.59–1.48 (m, 2H), 1.44–1.21 (m, 4H), 0.91 (t,
J = 6.7 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d = 141.2, 114.3, 73.2,
36.6, 27.4, 22.4, 13.8; MS (EI): m/z = 96 [MꢀH2O]+.
{½a 2D3
ꢁ
¼ þ29 (c 2.2, CHCl3), lit.3 ½a D23
¼ þ30 (c 2.1, CDCl3)}.
ꢁ
3. Conclusions
4.1.3. (R)-5-(4-Methoxybenzyloxy)pent-1-en-3-ol 4
To a solution of trimethylsulfonium iodide (5.8 g, 28.84 mmol)
in THF (40 mL) at ꢀ20 °C was added n-BuLi (1.6 M in hexane,
17.2 mL, 27.4 mmol) dropwise and the resulting solution was stir-
red for 1 h at ꢀ20 °C. After being stirred for 1 h, a solution of epox-
ide 8 (1.5 g, 7.21 mmol) in THF (10 mL) was added. The resultant
cloudy suspension was allowed to slowly warm to 25 °C over 1 h
and stirred for another 1 h. After consumption of the starting mate-
rial (monitored by TLC), the reaction mixture was quenched with
water. The layers were separated and the aqueous layer was ex-
tracted twice with EtOAc. The combined organic layers were dried
over Na2SO4 and concentrated under reduced pressure. Purification
by flash chromatography (10% EtOAc/hexanes) gave 1.5 g (93%) of
In conclusion, we have accomplished a stereoselective synthesis
of umuravumbolide by a combination of Wadsworth Emmons olef-
ination and silyl-tethered ring closing metathesis reactions in a
convergent fashion, with eight steps in the longest linear sequence
starting from ( )-1,2-epoxyhexane with 12.1% overall yield. This
strategy could readily be extended to a diverse range of coupling
partners in order to generate novel compound libraries for biolog-
ical evaluation. Further application of this strategy to the synthesis
of other naturally occurring 6-substituted 5,6-dihydro-
currently in progress in our laboratory.
a-pyrone is
4. Experimental
4.1. General
allylic alcohol 4 as a yellow oil. ½a D25
ꢁ
¼ ꢀ9:1 (c 1.8, CHCl3); IR (KBr):
3426, 2922, 2859, 1613, 1514, 1465, 1249, 1093, 820 cmꢀ1
;
1H
NMR (300 MHz, CDCl3): d = 7.26 (d, J = 8.83 Hz, 2H), 6.88 (d,
J = 8.83 Hz, 2H), 5.91–5.84 (m, 1H), 5.27 (d, J = 16.5, 1H), 5.1 (d,
J = 9.93 Hz, 1H), 4.45 (s, 2H), 4.36–4.31 (m, 1H), 3.81 (s, 3H),
3.71–3.66 (m, 1H), 3.64–3.59 (m, 1H), 1.89–1.77 (m, 2H); 13C
NMR (75 MHz, CDCl3): d = 159.2, 140.5, 129.9, 129.2, 114.2,
113.7, 72.8, 71.7, 67.9, 55.1, 36.2; ESI-HRMS: m/z [M+Na]+ calcd
for C13H18O3Na: 245.11504; found: 245.11482.
All reactions were conducted under an atmosphere of nitrogen
(IOLAR, Grade I). The apparatuses used for the reactions were oven
dried. THF was distilled over sodium benzophenone ketyl before
use, dichloromethane was distilled over calcium hydride. All re-
agents and solvents were reagent grade and used without further
purification unless specified otherwise. Column chromatography
was carried out with silica gel grade 60–120, and 100–200 mesh.
1H NMR spectra were recorded at 300 and 500 MHz and 13C
NMR at 75 MHz in CDCl3. IR spectra were recorded on FT/IR-
5700. Mass spectroscopic data were compiled using MS (ESI),
HRMS mass spectrometers. Optical rotations were recorded on a
polarimeter using 2 mL cell with a 1 dm path length.
4.1.4. (5R,9S)-7,7-Diisopropyl-1-(4-methoxyphenyl)-5,9-divinyl-
2,6,8-trioxa-7-silatridecane 9
Dichlorodiisopropylsilane (0.85 mL, 4.729 mmol) was added to
imidazole (1.53 g, 22.52 mmol) in CH2Cl2 (15 mL) at 0 °C. The solu-
tion was stirred for 5 min., then allylic alcohol 4 (1 g, 4.504 mmol)
in CH2Cl2 (10 mL) was added dropwise by a dropping funnel over
1 h at 0 °C. After the mixture was stirred for 10 min at 0 °C, a solu-
tion of allylic alcohol 3 (0.513 g, 4.504 mmol) in CH2Cl2 (5 mL) was
added at 0 °C. The reaction mixture was warmed to the room tem-
perature and stirred for 4 h and then purified directly by silica gel
column chromatography (EtOAc/n-hexane, 1:49), to afford 1.45 g
4.1.1. (S)-2-Butyloxirane 7
A mixture of (S,S)-N,N0-bis(3,5-di-tert-butylsalicyclidene-1,2-
cyclohexanediamino)cobalt(II) (0.175 g, 0.29 mmol) toluene
(5 mL) and AcOH (0.033 mL, 0.59 mmol) was stirred while open to
the air for 1 h at room temperature. After 1 h, the toluene and excess
acetic acid were removed under reduced pressure and the brown
residue was dried over high vacuum, after which ( )-1,2-epoxyhex-
ane (6 g, 59.89 mmol) was then added in one portion, the resultant
mixture was stirred for 30 min and cooled in an ice water bath.
Water (0.592 mL, 32.93 mmol) was added slowly and the tempera-
ture of the reaction mixture was maintained in such a way that it
never increased by more than 20 °C (1 h). The slurry was stirred
for 16 h and then subjected to distillation. Epoxide 2 was collected
at 120 °C (1 atm) (2.52 g, 42%). The recovered epoxide was exhibited
(72%) of bisalkoxysilane 9 as a colourless oil. ½a D25
¼ ꢀ36 (c 1.2,
ꢁ
CHCl3); IR (KBr): 2933, 2866, 1613, 1513, 1463, 1248, 1094, 993,
921, 682 cmꢀ1 1H NMR (300 MHz, CDCl3): d = 7.25 (d, J = 8.30 Hz,
;
2H), 6.87 (d, J = 8.30 Hz, 2H), 5.89–5.74 (m, 2H), 5.20–5.09 (m,
2H), 5.03 (td, J = 1.51, 10.57 Hz, 2H), 4.52–4.24 (m, 3H), 3.81 (s,
3H), 3.60–3.45 (m, 2H), 1.97–1.74 (m, 2H), 1.61–1.43 (m, 2H),
1.33–1.23 (m, 5H), 1.06–0.97 (m, 13H), 0.89 (t, J = 6.79 Hz, 3H);
13C NMR (75 MHz, CDCl3): d = 159.0, 141.4, 141.1, 130.7, 129.2,
113.9, 113.7, 73.6, 72.6, 70.9, 66.3, 55.2, 37.9, 37.7, 26.8, 22.7,
17.4, 14.1, 12.7; ESI-HRMS: m/z [M+Na]+ calcd for C26H44O4NaSi
471.28964; found: 471.9011.
½
a 2D0
ꢁ
¼ ꢀ8:2 (c 1, CHCl3), reported8b
½
a 2D0
ꢁ
¼ ꢀ9:0 (c 1.0, CHCl3).
4.1.2. (S)-Hept-1-en-3-ol 3
4.1.5. (R)-3-(((S)-Hept-1-en-3-yloxy)diisopropylsilyloxy)pent-4-
en-1-ol 10
To a solution of PMB ether 9 (1.2 g, 2.67 mmol) in CH2Cl2
(15 mL) and water (1.5 mL) at 0 °C was added DDQ (0.912 g,
To a solution of trimethylsulfonium iodide (8.14 g, 39.94 mmol)
in THF (40 mL) at ꢀ20 °C was added n-BuLi (1.6 M in hexane,
23.7 mL, 37.92 mmol) dropwise and the resulting solution was

T. V. Kumar et al. / Tetrahedron: Asymmetry 24 (2013) 594–598
597
4.01 mmol), and the reaction mixture was warmed to room tem-
perature and stirred for 1 h. The reaction was quenched with satu-
rated NaHCO3 (10 mL), and the organic layer was extracted with
CH2Cl2 (2 ꢂ 15 mL). The combined organic layer was washed with
brine (30 mL), dried over anhydrous Na2SO4 and the solvent was
evaporated to give a light red coloured product. Purification of
the crude product by silica gel column chromatography (EtOAc/
hexane, 1:19) afforded 10 (0.750 g, 85%) as a colourless liquid
1728, 1463, 1218, 772 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d = 7.07–6.95 (m, 1H), 5.90 (d, 1H, J = 11.46 Hz), 5.70–5.45 (m,
2H), 4.77–4.70 (m, 1H), 4.60–4.53 (m, 1H), 3.73 (s, 3H), 2.56–2.45
(m, 2H), 1.62–1.50 (m, 3 H), 1.41–1.26 (m, 4H), 1.06–0.98 (m,
13H), 0.91 (t, J = 6.79 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d = 166.8, 145.5, 136.4, 133.2, 123.0, 71.4, 69.8, 51.4, 41.2, 27.8,
22.5, 17.3, 17.16, 14.1, 12.9, 12.8; ESI-HRMS: m/z [M+Na]+ calcd
for C19H34O4NaSi: 377.21240; found: 377.21186.
½
a 2D5
ꢁ
¼ þ13:4 (c 3, CHCl3); IR (KBr): 3409, 2942, 2868, 1465,
1249, 1088, 1033, 921, 885, 683 cmꢀ1 1H NMR (300 MHz, CDCl3):
;
4.1.8. (R)-6-((S,Z)-3-Hydroxyhept-1-enyl)-5,6-dihydro-2H-pyran-
2-one 1a (desacetylumuravumbolide)
d = 5.96–5.75 (m, 2H), 5.29–5.06 (m, 4H), 4.65–4.59 (m, 1H), 4.30–
4.23 (m, 1H), 3.91–3.81 (m, 1H), 3.72–3.62 (m, 1H), 2.81–2.72 (m,
1H), 1.95–1.84 (m, 1H), 1.70–1.47 (m, 3H), 1.36–1.21 (m, 4H),
1.08–0.96 (m, 14H), 0.89 (t, J = 6.79 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d = 140.8, 140.7, 114.5, 113.9, 74.3, 71.2, 59.1, 39.4, 37.6,
26.9, 22.6, 17.2, 14.1, 12.6; ESI-HRMS: m/z [M+Na]+ calcd for
C18H36O3NaSi 351.23279; found 351.23259.
To a stirred solution of 11 (100 mg, 0.282 mmol) in THF (2 mL)
was added 3 M HCl (2 mL) at 0 °C after which the reaction mixture
warmed to room temperature and stirred for 6 h. After completion
of the reaction, the reaction mixture was quenched by the addition
of solid NaHCO3, filtered and the solvent was removed under
reduced pressure. The crude product was purified by silica gel
column chromatography (EtOAc/hexane, 3:7) to afford 1a as yel-
4.1.6. (R,Z)-Methyl 5-(((S)-hept-1-en-3-yloxy)diisopropylsilyloxy)
hepta-2,6-dienoate 2
low oil (47 mg, 80%). ½a D25
ꢁ
¼ ꢀ5:6 (c 1, CHCl3); IR (KBr): 3428,
2925, 2854 1718, 1382, 1249, 1024, 817, 772 cmꢀ1 1H NMR
;
To
a
stirred solution of primary alcohol 10 (300 mg,
(300 MHz, CDCl3): d = 6.94–6.88 (m, 1H), 6.05 (d, J = 10.0 Hz, 1H),
5.72–5.59 (m, 2 H), 5.38–5.29 (m, 1H), 4.46–4.38 (m, 1H), 2.52–
2.25 (m, 3H), 1.51–1.17 (m, 6 H), 0.90 (t, J = 6.79 Hz, 3H); 13C
NMR (75 MHz, CDCl3): d = 163.8, 144.7, 137.9, 127.4, 121.4, 73.6,
67.7, 36.7, 29.8, 27.4, 22.6, 14.0; ESI-HRMS: m/z [M+Na]+ calcd
for C12H18O3Na: 233.11494; found: 233.11482.
0.914 mmol) in CH2Cl2 (10 mL) was sequentially added solid NaH-
CO3 (305 mg, 3.658 mmol) and Dess–Martin periodinane (775 mg,
1.829 mmol). After stirring for 2 h at room temperature, the reac-
tion was quenched by the addition of aqueous Na2S2O3. The resul-
tant mixture was extracted with ethyl acetate (3 ꢂ 15 mL) and the
combined organic layer was washed with brine, dried over anhy-
drous Na2SO4, filtered and concentrated in vacuo, which was
directly carried to the next step without further purification. To a
stirred suspension of NaH (42.6 mg, 1.779 mmol) in dry THF
(10 mL) at 0 °C was added methyl-2-[bis(2,2,2-trifluoroeth-
oxy)phosphoryl]acetate (353 mg, 1.111 mmol) in THF (5 mL) and
then allowed to stir for 30 min. The reaction temperature was
4.1.9. (S,Z)-1-((R)-6-Oxo-3,6-dihydro-2H-pyran-2-yl)hept-1-en-
3-yl acetate 1b (umuravumbolide)
To a stirred solution of compound 1a (30 mg, 0.142 mmol) in dry
CH2Cl2 (2 mL) was added Et3N (0.047 mL, 0.342 mmol), acetic anhy-
dride(0.016 mL, 0.171 mmol), DMAP(3.5 mg, 0.0189 mmol) and the
resulting mixture was stirred at room temperature for 1 h. After
completion of the reaction, water was added, the organic layer
was separated and the aqueous phase was extracted with CH2Cl2
(3 ꢂ 5 mL). The combined organic layers were washed with brine,
dried over Na2SO4 and concentrated under reduced pressure. Purifi-
cation by silica gel column chromatography (EtOAc/hexane, 2:8)
brought to ꢀ78 °C, then
a solution of aldehyde (300 mg,
0.914 mmol) in dry THF (3 mL) was added dropwise over a period
of 10 min. The resulting mixture was stirred for 1 h at ꢀ78 °C. The
reaction was quenched with saturated NH4Cl and warmed to room
temperature. The layers were separated and the aqueous layer was
extracted with diethyl ether (3 ꢂ 8 mL). The combined organic
layer was washed with brine and dried over anhydrous Na2SO4. Re-
moval of the solvent under reduced pressure and separation of the
diastereomers by silica gel column chromatography (EtOAc/hex-
ane, 1:99) yielded Z-olefinic ester 2 (280 mg, 80% over two steps)
afforded 1b as a yellow oil (33 mg, 92%). ½a D25
¼ þ29 (c 2.2, CHCl3);
ꢁ
IR (KBr): 2921, 2861, 1740, 1711, 1376, 1235, 1022, 815,
768 cmꢀ1; 1H NMR (300 MHz, CDCl3): d = 6.88–6.82 (m, 1H), 6.04 (d,
J = 9.98 Hz, 1H), 5.74–5.68 (m, 1H), 5.56–5.50 (m, 1H), 5.45–5.36 (m,
2H), 2.49–2.41 (m, 1H), 2.31–2.24 (m, 1H), 2.02(s, 3H), 1.72–1.64(m,
as a colourless oil ½a D25
ꢁ
¼ ꢀ10:9 (c 1.2, CHCl3); IR (KBr): 3079,
1H),1.56–1.48(m,1H),1.36–1.20(m,4H),0.89(t,J = 6.99 Hz,3H);13
C
2926, 2866, 1727, 1647, 1463, 1175, 1033, 922, 814, 688 cmꢀ1
;
NMR (75 MHz, CDCl3): d = 170.2, 163.5, 144.3, 131.6, 130.0, 121.6,
74.0, 69.4, 34.2, 30.0, 27.2, 22.4, 21.1, 13.8; ESI-HRMS: m/z [M+Na]+
calcdforC14H20O4Na:275.12558;found:275.12538.
1H NMR (300 MHz, CDCl3): d = 6.37 (td, J = 6.29, 10.5 Hz, 1H),
5.86–5.76 (m, 3H), 5.24–5.01 (m, 4 H), 4.53 (q, J = 10.49 Hz, 2H),
4.29 (q, J = 12.59 Hz, 2H), 3.70 (s, 3H), 3.01–2.88 (m, 2H), 1.61–
1.45 (m, 3H), 1.33–1.24 (m, 4H), 1.04–0.99 (m, 13H), 0.88 (t,
J = 6.29 Hz, 3H); 13C NMR (75 MHz, CDCl3): d = 166.7, 141.3,
140.3, 120.4, 114.3, 113.8, 73.6, 71.8, 50.9, 37.7, 37.0, 26.8, 22.7,
17.4, 14.1, 12.7; ESI-HRMS: m/z [M+Na]+ calcd for C21H38O4NaSi:
405.24274; found: 405.24316.
Acknowledgments
T.V.K. thanks the CSIR, and G.V.R. thanks UGC New Delhi for the
award of fellowship.
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