Enantioselective syntheses of (-)-pinellic acid, α- and β-dimorphecolic acid

Article abstract of DOI:10.1016/j.tet.2007.05.047

An efficient enantioselective convergent approach for the synthesis of (-)-pinellic acid 1, α- and β-dimorphecolic acid (2 and 3) from 1,9-nonane diol is described. The synthetic strategy features Sharpless asymmetric hydroxylation, Sonogashira coupling and Birch reduction.

Full text of DOI:10.1016/j.tet.2007.05.047

Tetrahedron 63 (2007) 7624–7633
Enantioselective syntheses of (L)-pinellic acid,
a- and b-dimorphecolic acid
*
S. Vasudeva Naidu, Priti Gupta and Pradeep Kumar
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411-008, India
Received 6 February 2007; revised 26 April 2007; accepted 10 May 2007
Available online 17 May 2007
Abstract—An efficient enantioselective convergent approach for the synthesis of (ꢀ)-pinellic acid 1, a- and b-dimorphecolic acid (2 and 3)
from 1,9-nonane diol is described. The synthetic strategy features Sharpless asymmetric hydroxylation, Sonogashira coupling and Birch
reduction.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
However, its diene congener a-dimorphecolic acid 3 was
isolated from the plant Glechoma hederacea L. Labiatae7
(commonly known as ‘lierre terrestre’, ‘ground ivy’ or
‘creeping Charlie’), which has been demonstrated to be
a calcium specific ionophore,8 an inhibitor of acetylcholine
esterase (ACE)9 and aromatase,10 as well as being impli-
cated in the pathogenesis of familial Mediterranean fever.11
In addition, it can competitively inhibit enzyme activity
stimulated by PGEl and PGD2. This fatty acid has been pre-
viously isolated from Tragopogon porrifolius L. Composi-
tae12 and Xeranthemum annuurn Asso Compositae.13 It
has also been found in rice plants infected with blast dis-
ease14 and in bovine heart mitochondria.8 This fatty acid
contains structural features that are not typically found in
plant fatty acids, including a C-9 hydroxyl group and
C10–C12 conjugated double bonds, which possess a wealth
of biological properties.15 Owing to their lipid nature, long-
chain fatty acids play a vital role in maintaining cellular
properties,16 and consequently can elicit a variety of bio-
logical responses. Little is known about the biological
properties of b-dimorphecolic acid.
Influenza is an infectious disease that infects birds and
mammals (primarily in the upper airways and lungs in mam-
mals) and is caused by an RNA virus of the Orthomyxoviri-
dae family (the influenza viruses). The most common and
characteristic symptoms of influenza in humans are fever,
pharyngitis, myalgia, severe headache, coughing, and ma-
laise. Flu rapidly spreads around the world in seasonal epi-
demics,1 killing millions of people in pandemic years, and
hundreds of thousands in nonpandemic years.
Kampo medicine, ‘Sho-seiryu-to’ was found to possess
potent adjuvant activity by oral administration on nasal
influenza infection and nasal influenza vaccination.2 (ꢀ)-
Pinellic acid 1 (9S,12S,13S-trihydroxy-10E-octadecenoic
acid, Fig. 1) was isolated from the tubers of Pinellia ternata,
one of the eight component herbs of the Kampo formula,
Sho-seiryu-to (SST).3 Pinellic acid is a novel and potentially
useful oral adjuvant when used in conjunction with intrana-
sal inoculation of influenza HA vaccines.3a Pinellic acid
showed no haemolytic activity.3a Among the series of pine-
llic acid isomers, the (9S,12S,13S)-compound, which is a nat-
ural product, exhibited the most potent adjuvant activity.4
In the interest of evaluating the biological and pharmacolog-
ical properties of these compounds, it was necessary to
ꢀ
obtain sufficient quantities by chemical synthesis. Omura
Unsaturated hydroxy fatty acids (2–5) play an important role
in biological systems and were isolated from both animals
and plants. b-Dimorphecolic acid (2) is a unique hydroxydi-
enoid fatty acid, which was first isolated from the seed oil of
Dimorphotheca aurantiaca.5 It was also isolated from
Osteospermum aurantiaca5 and Osteospermum ecklonis.6
et al. reported the first synthesis of (ꢀ)-pinellic acid 1 and
determined its absolute configuration by synthesizing all
its isomers via regioselective Sharpless asymmetric di-
hydroxylation and stereoselective reduction,17a,b followed
by another recent synthesis by Sabitha et al. via Sharpless
asymmetric epoxidation.17c Rama Rao and co-workers18a
accomplished the first total synthesis of racemic dimorphe-
colic acid and coriolic acid 4 from tetrahydrofurfuryl
chloride. Subsequently Takeda and co-workers18b also syn-
thesized racemic dimorphecolic acid by using Grignard
Keywords: Asymmetric dihydroxylation; Sonogashira coupling; Influenza.
* Corresponding author. Tel.: +91 20 25902050; fax: +91 20 25902629;
e-mail: pk.tripathi@ncl.res.in
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.047

S. V. Naidu et al. / Tetrahedron 63 (2007) 7624–7633
7625
OH
OH
O
12S
HO
13S
9S
OH
pinellic acid (1)
OH
OH
H
OH
H
H
OH
HO
O
HO
HO
HO
O
O
O
β-dimorphecolic acid (2)
coriolic acid (4)
ricinoleic acid (5)
α-dimorphecolic acid (3)
Figure 1.
reactions. While Sato and co-workers19a accomplished ste-
reospecific synthesis of a-dimorphecolic acid by employing
CuI–Pd0 coupling as a key step, the enantioselective synthe-
sis of b-dimorphecolic acid 2 was reported by Ley and
Meek19b by utilizing a p-allyltricarbonyliron lactone com-
plex to control the formation of all the stereochemical fea-
tures of the natural product. As a part of our research
programme aimed at developing enantioselective synthesis
of naturally occurring lactones20 and amino alcohols,21 we
have accomplished the stereoselective total synthesis of
(ꢀ)-pinellic acid 1, a- and b-dimorphecolic acid (2 and 3)
starting from the commercially available starting material
1,9-nonane diol employing the Sharpless asymmetric di-
hydroxylation as the source of chirality.
2.1. Synthesis of chiral propargylic alcohol
The synthesis of (ꢀ)-pinellic acid 1, a- and b-dimorphecolic
acid (2 and 3) started from commercially available 1,9-non-
ane diol 6 as illustrated in Schemes 2 and 3. Thus, selective
b
a
HO
OH
PMBO
OH
7
7
7
6
OH
O
O
c
PMBO
OEt
PMBO
d
OEt
O
7
7
OH
O
9
8
O
e
O
PMBO
PMBO
PMBO
7
7
11
OH
O
OEt
10
2. Results and discussion
OP
O
O
g
f
PMBO
h
7
7
Our retrosynthetic strategy for the synthesis of (ꢀ)-pinellic
acid 1, a- and b-dimorphecolic acid (2 and 3) is outlined
in Scheme 1. We envisioned that the 12S,13S syn-diol 17
could be prepared from 1,3-enyne 16, which in turn would
be prepared by Sonogashira coupling22 of chiral propargylic
alcohol 13 with vinyl iodide 15. Chiral propargylic alcohol
13 could be prepared from 1,9-nonane diol 6, through base
induced elimination of chloro compound 12. In this strategy,
the 9S hydroxy group could be installed through Sharpless
asymmetric dihydroxylation23 of an olefin 8, which in turn
would be prepared from 1,9-nonane diol 6.
Cl
13: P = H
14: P = TBDPS
12
Scheme 2. Reagents and conditions: (a) p-CH3OC6H4CH2Br, NaH, dry
DMF, cat. TBAI, 0 ꢁC to rt, 1 h, 95%; (b) (i) (COCl)2, DMSO, Et3N,
CH2Cl2, ꢀ78 ꢁC to ꢀ60 ꢁC; (ii) Ph3P]CHCO2Et, benzene, reflux, 4 h,
91%; (c) (DHQ)2PHAL, K2CO3, K3Fe(CN)6, MeSO2NH2, OsO4 (0.1 M
solution in toluene), t-BuOH/H2O (1:1), 0 ꢁC, 24 h, 96%; (d) p-TSA, 2,2-
DMP, CH2Cl2, overnight, 94%; (e) DIBAL-H, CH2Cl2, 0 ꢁC to rt, 2 h,
95%; (f) N-chlorosuccinimide, PPh3, CH2Cl2, 0 ꢁC to rt, 3 h, 89%; (g)
n-BuLi, HMPA, THF, ꢀ42 ꢁC to rt, 30 min, 82%; (h) TBDPSCl, imidazole,
CH2Cl2, 0 ꢁC to rt, overnight, 98%.
Sonogashira
Reduction
Reduction
Sonogashira
coupling
13
coupling
OH
OH
OH
O
O
HO
HO
1
9
12
AD
AD
OH
1
2 = E C12-C13
3 = Z C12-C13
AD
OTBDPS
I
OTBDPS
OH
15
PMBO
7
+
OH
PMBO
7
17
OH
16
PMBO
7
13
O
OH
O
O
AD
O
HO
OH
7
PMBO
7
OEt
PMBO
7
OEt
PMBO
12
7
6
9
8
OH
Cl
Scheme 1. Retrosynthetic analysis of (ꢀ)-pinellic acid (1), a- and b-dimorphecolic acid (2 and 3).

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S. V. Naidu et al. / Tetrahedron 63 (2007) 7624–7633
OTBDPS
OTBDPS
b
OH
O
a
PMBO
PMBO
7
7
14 + 15
17
16
OH
OTBDPS
OTBDPS
OH
d
c
HO
O
7
HO
7
19
O
18
OH
O
OTBDPS
OH
OH
f
e
HO
7
HO
7
O
O
OH
(-)-Pinellic acid (1)
20
Scheme 3. Reagents and conditions: (a) Pd(PPh3)2Cl2, CuI, Et3N, 6 h, 86%; (b) (DHQ)2PHAL, K2CO3, K3Fe(CN)6, MeSO2NH2, OsO4 (0.1 M solution in
toluene), t-BuOH/H2O 1:1, 0 ꢁC, 24 h, 91%; (c) Na/liq NH3, THF, ꢀ40 ꢁC, 90%; (d) p-TSA, 2,2-DMP, CH2Cl2, overnight, 92%; (e) (i) IBX, EtOAc, reflux,
5 h; (ii) NaClO2, DMSO, NaH2PO4, rt, overnight, 81%; (f) HCl (cat.), MeOH, rt, overnight, 78%.
mono protection of 6 with p-methoxybenzyl bromide in the
presence of NaH gave the monoprotected diol 7 in 95%
yield, which was oxidized to the corresponding aldehyde
under Swern conditions,24 and subsequently treated with
(ethoxycarbonylmethylene)-triphenylphosphorane in benz-
ene at reflux to furnish the trans-olefin 8 in 91% yield. Ole-
fin 8 was treated with osmium tetroxide and potassium
ferricyanide as co-oxidant in the presence of (DHQ)2PHAL
ligand under asymmetric dihydroxylation (AD) conditions23
to give the diol 9 in 96% yield with 99% ee. Treatment
of diol 9 with 2,2-dimethoxypropane in the presence of
p-TSA gave compound 10, which on reduction with
DIBAL-H furnished the alcohol 11 in excellent yield. The
alcohol 11 was converted to chloride 12 in 89% yield.
Propargylic alcohol 13 was obtained by treatment of 12
with n-BuLi in the presence of HMPA25 in 82% yield. The
free hydroxy group of 13 was protected with TBDPSCl to
furnish compound 14.
under acidic conditions (catalytic HCl in MeOH) to afford
the target molecule 1 in 78% overall yield from 19. The
physical and spectroscopic data of 1 were identical with
those reported.17
2.3. Synthesis of b-dimorphecolic acid (2)
After completion of the synthesis of (ꢀ)-pinellic acid 1, we
then further proceeded with the synthesis of b-dimorphe-
colic acid 2 from 1,3-enyne product 21 (Scheme 4). Thus,
coupling of 13 with trans-vinyl iodide 15 using
Pd(PPh3)2Cl2 and CuI in triethylamine furnished the 1,3-
enyne product 21 in 86% yield. Reduction of 21 proceeded
smoothly with the required (E)-geometry of the alkene using
LAH in refluxing THF to afford 22 in good yield. The free
hydroxy group of 22 was protected with TBDPSCl followed
by deprotection of the PMB group with DDQ30 to furnish
compound 24 in good yield. Oxidation of the primary alco-
hol in 24 to the corresponding aldehyde using Swern condi-
tions24 and further oxidation using NaClO2 in DMSO under
buffer conditions29 afforded the acid 25. Finally, the TBDPS
group was deprotected using TBAF to afford the target mol-
ecule 2 in 89% yield. The physical and spectroscopic data of
2 were identical with those reported.18,19,31
2.2. Synthesis of (L)-pinellic acid (1)
Having completed the synthesis of chiral propargylic
alcohol 14, our next aim was to prepare enyne 16 through
Sonogashira coupling22 and carry out subsequent transfor-
mations in order to get the target molecule 1. Towards this,
the coupling of 14 with trans-vinyl iodide 1526 using
Pd(PPh3)2Cl2 and CuI in triethylamine furnished the 1,3-
enyne product 16 in excellent yield (Scheme 3). Asymmetric
dihydroxylation23 of 1,3-enyne 16 under standard conditions
gave the acetylenic diol 17 in good yield with high diastereo-
OH
a
b
PMBO
13 + 15
7
21
OP
OTBDPS
1
meric excess (de >96%) as judged by H and 13C NMR
d
PMBO
7
HO
7
spectral analysis. Reduction of alkyne 17 to the (E)-alkene
and concomitant removal of the PMB group proceeded
smoothly under Birch conditions using Na/liq NH3 to
22 : P = H
23 : P = TBDPS
24
c
27
afford 18 in 90% yield. Diol 18 was protected as its iso-
propylidene derivative 19 in the presence of 2,2-dimethoxy-
propane and a substoichiometric amount of p-TSA in good
yield.
O
OH
O
OTBDPS
HO
7
f
HO
7
e
25
2
Scheme 4. Reagents and conditions: (a) Pd(PPh3)2Cl2, CuI, Et3N, 8 h, 86%;
(b) LAH, THF, 0 ꢁC to rt, 83%; (c) TBDPSCl, imidazole, CH2Cl2, 0 ꢁC to rt,
overnight, 96%; (d) DDQ, CH2Cl2/H2O (9:1), 89%; (e) (i) (COCl)2, DMSO,
Et3N, CH2Cl2, ꢀ78 ꢁC to ꢀ60 ꢁC; (ii) NaClO2, DMSO, H2O, NaH2PO4, rt,
1.5 h; (f) TBAF, THF, rt, overnight, 89%.
Oxidation of the primary alcohol in 19 to the corresponding
aldehyde using IBX28 and further oxidation using NaClO2 in
DMSO under buffered conditions29 furnished the acid 20.
Finally, the acetonide and TBDPS groups were deprotected

S. V. Naidu et al. / Tetrahedron 63 (2007) 7624–7633
7627
2.4. Synthesis of a-dimorphecolic acid
4. Experimental
4.1. General methods
To achieve the synthesis of a-dimorphecolic acid, chiral
propargylic alcohol 14 was converted into (E)-vinyl iodide
through a vinyl stannane (Scheme 5). Thus, acetylene 14
was readily converted into (E)-vinyl stannane 26 by reaction
with tri-n-butyltin hydride and AIBN in refluxing benzene in
99% yield. Tributyltin was then replaced with iodide by using
I2 in CH2Cl232 to afford the corresponding iodo compound 27
in excellent yield. The Sonogashira coupling22 of 27 with
commercially available 1-heptyne 28 was successfully
carried out using Pd(PPh3)2Cl2 and CuI in triethylamine to
furnish the 1,3-enyne product 29 in good yield. The partial
hydrogenation of the triple bond in 29 proved to be challeng-
ing. Irrespective of whether substoichiometric quantities or
several molar equivalents of quinoline were present, the mix-
ture of 30 and over hydrogenated product was formed. The
use of 1-octene as a co-solvent along with EtOAc in the pres-
ence of pyridine (EtOAc/pyridine/1-octene ¼10:1:1)33 fur-
nished the diene 30 as a single product. The subsequent
deprotection of the p-methoxybenzyl group with DDQ30
furnished the alcohol 31 in 94% yield. Oxidation of the
resulting alcohol to the corresponding aldehyde using Swern
conditions24 and further oxidation using sodium chlorite in
DMSO under buffer conditions29 afforded the acid. Finally,
the TBDPS group was deprotected using TBAF to afford
the target molecule 3 in good yield. The physical and spectro-
scopic data of 3 were identical with those reported.18
All reactions were carried out under argon or nitrogen in
oven-dried glassware using standard gas-light syringes, can-
nulas and septa. Solvents and reagents were purified and
dried by standard methods prior to use. Optical rotations
were measured at room temperature. IR spectra were
recorded on an FT-IR instrument. 1H NMR spectra were re-
corded at 200 MHz, 300 MHz and 500 MHz and are reported
in parts per million (d) downfield relativeto CDCl3 as internal
standard and 13C NMR spectra were recorded at 50 MHz,
75 MHz and 125 MHz and assigned in parts per million (d)
relative to CDCl3. Column chromatography was performed
on silica gel (100–200 and 230–400 mesh) using a mixture
of petroleum ether and ethyl acetate as the eluent. Enantio-
meric excess was determined using chiral HPLC.
4.1.1. 9-(4-Methoxybenzyloxy)nonan-1-ol (7). To a solu-
tion of 1,9-nonane diol 4 (8.0 g, 49.92 mmol) in dry DMF
(200 mL) was added sodium hydride (50%, 2.64 g,
77.70 mmol) at 0 ꢁC. The reaction mixture was then stirred
atroomtemperaturefor30 minafterwhichitwasagaincooled
to 0 ꢁC. To this was added slowly p-methoxybenzyl bromide
(10.04 g, 49.92 mmol) and tetra n-butylammonium iodide
(1.84 g, 4.99 mmol) with further stirring for 1 h at the same
temperature. The reaction mixture was quenched with addi-
tion of cold water at 0 ꢁC. The two phases were separated
and the aqueous phase was extracted with EtOAc (3ꢂ
100 mL). The combined organic layers were washed with wa-
ter (3ꢂ100 mL), brine, dried (Na2SO4) and concentrated. The
residual oil was purified by silica gel column chromatography
using petroleum ether/EtOAc (8:2) as eluent to furnish the
mono-PMB protected alcohol 7 (13.31 g, 95%) as a colourless
oil. IR(CHCl3):n¼3400, 2937, 2863, 1612, 1513, 1248, 1174,
1097 cmꢀ1; 1H NMR (200 MHz, CDCl3): d¼1.27–1.42 (m,
10H), 1.52–1.64 (m, 4H), 3.49 (t, J¼5.0 Hz, 2H), 3.62 (t, J¼
5.0 Hz, 2H), 3.81 (s, 3H), 4.48 (s, 2H), 6.88 (d, J¼10.0 Hz,
2H), 7.26 (d, J¼10.0 Hz, 2H); 13C NMR (50 MHz, CDCl3):
d¼13.9, 26.1, 27.8, 28.9, 29.1, 29.6, 55.1, 62.2, 69.9, 72.5,
113.8, 129.2, 130.4, 159.2. Anal. Calcd for C17H28O3
(280.40): C, 72.82; H, 10.06%. Found: C, 72.99; H, 9.87%.
OTBDPS
a
b
14
PMBO
SnBu3
7
26
OTBDPS
OTBDPS
c
PMBO
7
PMBO
I
7
29
27
OTBDPS
e
d
PMBO
7
30
O
OH
OTBDPS
f
HO
HO
7
7
31
3
4.1.2. (E)-Ethyl 11-(4-methoxybenzyloxy)undec-2-enoate
(8). To a solution of oxalyl chloride (4.75 g, 37.44 mmol) in
dry CH2Cl2 (100 mL) at ꢀ78 ꢁC was added dropwise dry
DMSO (5.85 g, 5.3 mL, 74.89 mmol) in CH2Cl2 (20 mL).
After 30 min, alcohol 7 (7.0 g, 24.96 mmol) in CH2Cl2
(20 mL) was added over 10 min giving a copious white pre-
cipitate. After stirring for 1 h at ꢀ78 ꢁC the reaction mixture
was brought to ꢀ60 ꢁC and Et3N (10.10 g, 13.9 mL,
99.85 mmol) was added slowly and stirred for 30 min allow-
ing the reaction mixture to warm to room temperature. The
reaction mixture was then diluted with water (150 mL) and
CH2Cl2. The organic layer was separated and washed with
water and brine, dried (Na2SO4) and passed through short
pad of Celite. The filtrate was concentrated to give the alde-
hyde (9.86 g, 95%) as pale yellow oil, which was used as
such for the next step without purification.
Scheme 5. Reagents and conditions: (a) (n-Bu)3SnH, AIBN, C6H6, reflux,
4 h, 99%; (b) I2, CH2Cl2, 30 min, 96%; (c) Pd(PPh3)2Cl2, CuI, Et3N, 1-hep-
tyne (28), 6 h, 89%; (d) H2, Lindlar’s catalyst, EtOAc/pyridine/1-octene
(10:1:1), 6 h, 95%; (e) DDQ, CH2Cl2/H2O (9:1), 94%; (f) (i) (COCl)2,
DMSO, Et3N, CH2Cl2, ꢀ78 ꢁC to ꢀ60 ꢁC, 95%; (ii) NaClO2, DMSO,
H2O, NaH2PO4, rt, 1.5 h, 86%.
3. Conclusions
In conclusion, efficient total syntheses of (ꢀ)-pinellic acid 1,
a- and b-dimorphecolic acid (2 and 3) with high enantio-
selectivity have been developed in which all the stereo-
centres were established by Sharpless asymmetric
dihydroxylation. Notable features of this approach include
Sonogashira coupling, reduction to establish the trans- and
cis-olefin geometry. Further application of this methodology
to the syntheses of related compounds for structure–activity
relationship studies is currently underway in our laboratory.
To a solution of (ethoxycarbonylmethylene)triphenyl-phos-
phorane (10.5 g, 30.17 mmol) in dry benzene (150 mL)

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S. V. Naidu et al. / Tetrahedron 63 (2007) 7624–7633
was added a solution of the above aldehyde in dry benzene
(100 mL). The reaction mixture was refluxed for 4 h. It
was then concentrated and purified by silica gel column
chromatography using petroleum ether/EtOAc (8.5:1.5) as
eluent to afford the a,b-unsaturated olefin 8 (7.92 g, 91%)
as a pale yellow liquid. IR (CHCl3): n¼2956, 2858, 1724,
2H), 7.30 (d, J¼8.8 Hz, 2H); 13C NMR (50 MHz, CDCl3):
d¼13.8, 25.4, 25.6, 25.9, 29.2, 29.3, 29.6, 54.8, 60.9, 69.3,
72.3, 78.7, 110.5, 113.5, 128.8, 130.3, 158.9, 172.5. Anal.
Calcd for C24H38O6 (422.56): C, 68.22; H, 9.06%. Found:
C, 68.01; H, 9.21%.
1
1654, 1038, 1300, 1204, 1100 cmꢀ1; H NMR (200 MHz,
4.1.5. ((4S,5S)-5-(8-(4-Methoxybenzyloxy)octyl)-2,2-di-
methyl-1,3-dioxolan-4-yl)methanol (11). To a solution of
10 (5.0 g, 11.83 mmol) in dry CH2Cl2 (80 mL) at 0 ꢁC was
added dropwise DIBAL-H (17.7 mL, 17.74 mmol, 1.0 M so-
lution in toluene) through a syringe. The reaction mixture
was allowed to warm to room temperature over 2 h, then
re-cooled to 0 ꢁC and treated with saturated solution of
sodium/potassium tartrate. The solid material was filtered
through a pad of Celite and concentrated. Silica gel column
chromatography of the crude product using petroleum ether/
EtOAc (7:3) as eluent gave 11 (4.28 g, 95%) as a colourless
oil. [a]2D5 ꢀ13.05 (c 1.6, CHCl3); IR (CHCl3): n¼3440, 2938,
CDCl3): d¼1.30–1.37 (m, 11H), 1.48–1.68 (m, 4H), 2.28
(q, J¼7.0 Hz, 2H), 3.48 (t, J¼6.0 Hz, 2H), 3.85 (s, 3H),
4.25 (q, J¼8.0 Hz, 2H), 4.48 (s, 2H), 5.90 (d, J¼15.0 Hz,
1H), 6.91 (d, J¼8.0 Hz, 2H), 6.98 (dt, J¼15.0, 10.0 Hz,
1H), 7.30 (d, J¼8.0 Hz, 2H); 13C NMR (50 MHz, CDCl3):
d¼14.1, 26.0, 27.8, 28.9, 29.1, 29.6, 32.0, 54.9, 59.9, 69.9,
72.3, 113.5, 121.1, 128.9, 130.6, 149.1, 158.9, 166.5. Anal.
Calcd for C21H32O4 (348.48): C, 72.38; H, 9.26%. Found:
C, 72.52; H, 9.11%.
4.1.3. (2R,3S)-Ethyl 11-(4-methoxybenzyloxy)-2,3-di-
hydroxyundecanoate (9). To a mixture of K3Fe(CN)6
(17.01 g, 51.65 mmol), K2CO3 (7.14 g, 51.65 mmol) and
(DHQ)2PHAL (134 mg, 1 mol %), in t-BuOH/H2O (1:1,
175 mL) cooled at 0 ꢁC was added OsO4 (0.70 mL, 0.1 M
solution in toluene, 0.4 mol %) followed by methanesulfon-
amide (1.64 g, 17.22 mmol). After being stirred for 5 min
at 0 ꢁC, the olefin 8 (6.0 g, 17.22 mmol) was added in one
portion. The reaction mixture was stirred at 0 ꢁC for 24 h
and then quenched with solid sodium sulfite (25 g). The stir-
ring was continued for an additional 45 min, and then the so-
lution was extracted with EtOAc (3ꢂ50 mL). The combined
organic extracts were washed with 10% KOH and brine,
dried (Na2SO4) and concentrated. Silica gel column chroma-
tography of the crude product using petroleum ether/EtOAc
(3:2) as eluent gave the diol 9 (6.32 g, 96%) as a colourless
syrupy liquid. The enantiomeric purity of the diol 9 was es-
timated to be >99% by chiral HPLC analysis (Chiralcel OD,
petroleum ether/i-PrOH (96:4), 1 mL/min, 240 nm). [a]D25
ꢀ6.7 (c 1.7, CHCl3); IR (CHCl3): n¼3440, 2938, 2864,
1
2860, 1361, 1204, 1126, 1038 cmꢀ1; H NMR (200 MHz,
CDCl3): d¼1.28–1.40 (m, 10H), 1.41 (s, 3H), 1.42 (s, 3H),
1.51–1.63 (m, 4H), 2.18 (s, 1H), 3.46–3.54 (m, 2H), 3.61
(dd, J¼7.5, 4.4 Hz, 1H), 3.76 (m, 2H), 3.81 (s, 3H), 3.90 (dt,
J¼7.6, 4.0 Hz, 1H), 4.44 (s, 2H), 6.89 (d, J¼8.7 Hz, 2H),
7.25 (d, J¼8.7 Hz, 2H); 13C NMR (50 MHz, CDCl3): d¼
25.4, 25.9, 26.9, 27.2, 29.3, 29.4, 29.7, 55.2, 62.1, 69.7, 72.4,
76.7, 81.6, 108.4, 113.7, 129.1, 130.5, 159.1. Anal. Calcd
for C22H36O5 (380.52): C, 69.44; H, 9.54%. Found: C,
69.62; H, 9.33%.
4.1.6. (4S,5R)-4-(8-(4-Methoxybenzyloxy)octyl)-5-(chloro-
methyl)-2,2-dimethyl-1,3-dioxolane (12). To a solution
of alcohol 11 (5.0 g, 13.14 mmol) and Ph3P (4.14 g,
15.77 mmol) in dry CH2Cl2 (50 mL) was added NCS
(2.11 g, 15.77 mmol) at 0 ꢁC under nitrogen. The reaction
mixture was stirred at 0 ꢁC for 1 h, then allowed to warm
to room temperature, and stirred for 2 h. The mixture was di-
luted with 100 mL of hexane and passed through a pad of
Celite under suction to remove the precipitate of Ph3PO.
The filtrate was concentrated, and resulting residue was dis-
solved in 100 mL of hexane and passed through a pad of Cel-
ite to remove the precipitate of Ph3PO again. Evaporation of
solvent gave 12 (4.67 g, 89%) as a colourless oil. [a]2D5 ꢀ5.6
(c 0.5, CHCl3); 1H NMR (200 MHz, CDCl3): d¼1.29 (br s,
10H), 1.40 (s, 3H), 1.41 (s, 3H), 1.52–1.61 (m, 4H), 3.42 (t,
J¼6.6 Hz, 2H), 3.57 (d, J¼4.7 Hz, 2H), 3.79 (s, 3H), 3.84–
3.88 (m, 2H), 4.42 (s, 2H), 6.88 (d, J¼8.6 Hz, 2H), 7.23 (d,
J¼8.7 Hz, 2H); 13C NMR (50 MHz, CDCl3): d¼25.8, 26.1,
27.0, 27.5, 29.3, 29.5, 29.7, 33.5, 44.4, 55.2, 70.2, 72.5, 79.4,
80.3, 109.1, 113.8, 129.1, 130.9, 159.1. Anal. Calcd for
C22H35ClO4 (398.96): C, 66.23; H, 8.84; Cl, 8.89%. Found:
C, 66.45; H, 8.66; Cl, 8.92%.
1736, 1612, 1513, 1248, 1130, 1032 cmꢀ1 1H NMR
;
(200 MHz, CDCl3): d¼1.25–1.36 (m, 13H), 1.50–1.74 (m,
4H), 2.51 (br s, 2H), 3.46 (t, J¼6.6 Hz, 2H), 3.82 (s, 3H),
3.90 (d, J¼6.6 Hz, 1H), 4.06–4.16 (m, 1H), 4.32 (q, J¼
7.0 Hz, 2H), 4.46 (s, 2H), 6.93 (d, J¼8.5 Hz, 2H), 7.31 (d,
J¼8.5 Hz, 2H); 13C NMR (50 MHz, CDCl3): d¼14.0, 25.5,
26.0, 29.2, 29.3, 29.5, 33.5, 55.0, 61.6, 70.0, 72.3, 73.0, 73.1,
113.6, 128.9, 130.7, 158.9, 173.4. Anal. Calcd for C21H34O6
(382.50): C, 65.94; H, 8.96%. Found: C, 66.09; H, 8.81%.
4.1.4. (4S,5S)-Ethyl 5-(8-(4-methoxybenzyloxy)octyl)-
2,2-dimethyl-1,3-dioxolane-4-carboxylate (10). To a solu-
tion of the diol 9 (5.0 g, 13.07 mmol), p-TSA (100 mg) in
CH2Cl2 (100 mL) was added 2,2-dimethoxypropane (2.0 g,
19.61 mmol) and the reaction mixture stirred overnight at
room temperature. Solid NaHCO3 (1 g) was added and the
mixture again stirred for 30 min. The reaction mixture was
filtered through a pad of neutral alumina and the filtrate con-
centrated. Silica gel column chromatography using petro-
leum ether/EtOAc (9:1) as eluent gave 10 (5.19 g, 94%) as
a colourless liquid. [a]D25 ꢀ23.1 (c 1.7, CHCl3); IR (neat):
4.1.7. (S)-11-(4-Methoxybenzyloxy)undec-1-yn-3-ol (13).
To a solution of HMPA (11.43 g, 70.18 mmol) in dry THF
(20 mL) was added n-BuLi (70.20 mL, 70.18 mmol, 1.0 M
solution in hexane) at ꢀ42 ꢁC under N2. After 10 min, a so-
lution of chloride 12 (4.0 g, 10.03 mmol) in THF (10 mL)
was added dropwise over 5 min. The reaction mixture was
warmed to room temperature and stirred for another 0.5 h.
Saturated aqueous NH4Cl solution was added to quench
the reaction. The product was extracted with EtOAc (3ꢂ
30 mL), and combined organic layers were washed with
brine, dried (Na2SO4) and concentrated. Silica gel column
1
n¼2864, 1736, 1612, 1513, 1248, 1130, 1032 cmꢀ1; H
NMR (200 MHz, CDCl3): d¼1.29–1.40 (m, 13H), 1.46 (s,
3H), 1.49 (s, 3H), 1.56–1.63 (m, 2H), 1.66–1.80 (m, 2H),
3.45 (t, J¼6.6 Hz, 2H), 3.82 (s, 3H), 4.11–4.14 (m, 2H),
4.25 (q, J¼7.32 Hz, 2H), 4.45 (s, 2H), 6.91 (d, J¼8.8 Hz,

S. V. Naidu et al. / Tetrahedron 63 (2007) 7624–7633
7629
chromatography of the crude product using petroleum ether/
EtOAc (7:3) as eluent gave 13 (2.50 g, 82%) as a colourless
oil. [a]2D5 ꢀ1.75 (c 0.76, CHCl3); 1H NMR (200 MHz,
CDCl3): d¼1.33–1.51 (m, 10H), 1.59–1.79 (m, 4H), 1.86
(br s, 1H), 2.48 (d, J¼2.0 Hz, 1H), 3.46 (t, J¼6.6 Hz, 2H),
3.83 (s, 3H), 4.39 (dd, J¼6.6, 1.8 Hz, 1H), 4.46 (s, 2H),
6.93 (d, J¼8.2 Hz, 2H), 7.31 (d, J¼8.5 Hz, 2H); 13C NMR
(50 MHz, CDCl3): d¼24.8, 25.9, 28.9, 29.1, 29.2, 29.4,
37.4, 55.0, 61.7, 69.9, 72.2, 72.4, 85.1, 113.5, 129.1, 130.4,
158.8. Anal. Calcd for C19H28O3 (304.42): C, 74.96; H,
9.27%. Found: C, 74.81; H, 9.39%.
filtered through Celite and filtrate was concentrated. Silica
gel column chromatography of the crude product using
petroleum ether/EtOAc (9:1) as eluent gave 16 (1.36 g,
86%) as a pale yellow oil. [a]2D5 3.5 (c 0.51, CHCl3); IR
(CHCl3): n¼2952, 2854, 1615, 1514, 1232, 1132,
1
1030 cmꢀ1; H NMR (200 MHz, CDCl3): d¼0.91 (t, J¼
6.4 Hz, 3H), 1.09 (s, 9H), 1.22–1.43 (m, 16H), 1.56–1.72
(m, 4H), 2.06 (q, J¼7.0 Hz, 2H), 3.44 (t, J¼6.6 Hz, 2H),
3.81 (s, 3H), 4.44 (s, 2H), 4.47–4.54 (m, 1H), 5.38 (dd, J¼
15.8, 1.6 Hz, 1H), 5.76–5.97 (m, 1H), 6.91 (d, J¼8.7 Hz,
2H), 7.30 (d, J¼8.7 Hz, 2H), 7.36–7.43 (m, 6H), 7.68–7.79
(m, 4H); 13C NMR (50 MHz, CDCl3): d¼14.0, 19.3, 22.4,
24.9, 26.1, 27.0, 28.4, 29.2, 29.4, 29.8, 31.2, 32.9, 38.4,
55.2, 64.4, 70.2, 72.5, 83.7, 89.2, 109.1, 113.7, 134.8,
135.9, 136.1, 144.0, 159.1. Anal. Calcd for C42H58O3Si
(638.99): C, 78.94; H, 9.15; Si, 4.40%. Found: C, 78.76;
H, 9.33; Si, 4.58%.
4.1.8. ((S)-11-(4-Methoxybenzyloxy)undec-1-yn-3-yloxy)
(tert-butyl)diphenylsilane (14). A stirred solution of
compound 13 (3.0 g, 9.85 mmol) and imidazole (1.0 g,
14.78 mmol) in dry CH2Cl2 (30 mL) was treated under
argon with TBDPSCl (3.0 g, 10.84 mmol) at 0 ꢁC and the
reaction mixture was stirred overnight at the same tempera-
ture. The reaction mixture was quenched by addition of
aqueous NH4Cl (30 mL) and the mixture was extracted
with CH2Cl2 (3ꢂ50 mL). The combined extracts were dried
(Na2SO4) and concentrated. Silica gel column chromato-
graphy of the crude product using petroleum ether/EtOAc
(9.5:0.5) as eluent gave the compound 14 (5.24 g, 98%) as
a colourless syrupy liquid. [a]2D5 ꢀ22.3 (c 1.9, CHCl3); IR
(CHCl3): n¼3440, 2938, 2864, 1736, 1612, 1513, 1248,
1130, 1032 cmꢀ1; 1H NMR (200 MHz, CDCl3): d¼1.10 (s,
9H), 1.24 (br s, 10H), 1.53–1.72 (m, 4H), 2.33 (d, J¼
2.0 Hz, 1H), 3.44 (t, J¼6.6 Hz, 3H), 3.82 (s, 2H), 3.35 (ddd,
J¼6.1, 1.9 Hz, 1H), 4.45 (s, 2H), 6.92 (d, J¼8.7 Hz, 2H),
7.31 (d, J¼8.6 Hz, 2H), 7.37–7.45 (m, 6H), 7.64–7.79 (m,
4H); 13C NMR (50 MHz, CDCl3): d¼19.2, 24.3, 24.5,
26.1, 26.5, 26.8, 28.9, 29.25, 29.28, 29.65, 37.2, 38.1, 55.0,
63.6, 69.2, 70.0, 72.4, 85.0, 113.6, 117.0, 127.3, 127.5,
129.1, 129.4, 129.56, 129.65, 129.7, 130.7, 133.9, 134.7,
135.7, 135.9, 159.0. Anal. Calcd for C35H46O3Si (542.82):
C, 77.44; H, 8.54%. Found: C, 77.51; H, 8.45%.
4.1.11. (6S,7S,10S)-10-(tert-Butyldiphenylsilyloxy)-18-(4-
methoxybenzyloxy)octadec-8-yne-6,7-diol (17). To a mix-
ture of K3Fe(CN)6 (1.55 g, 4.69 mmol), K2CO3 (649 mg,
4.69 mmol) and (DHQ)2PHAL (12 mg, 1 mol %), in t-
BuOH/H2O (1:1, 20 mL) cooled at 0 ꢁC was added OsO4
(0.06 mL, 0.1 M solution in toluene, 0.4 mol %) followed
by methanesulfonamide (149 mg, 1.56 mmol). After being
stirred for 5 min at 0 ꢁC, the olefin 16 (1.0 g, 1.56 mmol)
was added in one portion. The reaction mixture was stirred
at 0 ꢁC for 24 h and then quenched with solid sodium sulfite
(25 g). The stirring was continued for an additional 45 min,
and then the solution was extracted with EtOAc (3ꢂ50 mL).
The combined organic extracts were washed with brine,
dried (Na2SO4) and concentrated. Silica gel column chroma-
tography of the crude product using petroleum ether/EtOAc
(3:2) as eluent gave the diol 17 (941 mg, 91%) as a colourless
syrupy liquid. [a]D25 +8.8 (c 0.9, CHCl3); IR (CHCl3): nmax
3440, 2938, 2864, 1736, 1612, 1513, 1248, 1130,
1
1032 cmꢀ1; H NMR (200 MHz, CDCl3): d 0.90 (t, J¼
6.8 Hz, 3H), 1.07 (s, 9H), 1.27 (br s, 18H), 1.57–1.73 (m,
4H), 2.34 (br s, 2H), 3.29–3.34 (m, 2H), 3.81 (s, 3H), 3.90
(t, J¼7.3 Hz, 2H), 4.23–4.34 (m, 1H), 4.45 (s, 2H), 6.91
(d, J¼8.7 Hz, 2H), 7.30 (d, J¼8.7 Hz, 2H), 7.35–7.49 (m,
6H), 7.69–7.78 (m, 4H); 13C NMR (50 MHz, CDCl3): d¼
13.9, 19.1, 22.5, 24.8, 25.1, 26.1, 26.8, 29.0, 29.3, 29.4,
29.7, 31.7, 32.1, 38.2, 55.2, 63.7, 65.9, 70.1, 72.4, 74.5,
83.2, 87.7, 113.7, 127.3, 127.6, 129.2, 129.6, 129.8, 130.7,
133.4, 134.1, 135.8, 135.9, 159.1. Anal. Calcd for
C42H60O5Si (673.01): C, 74.95; H, 8.99; Si, 4.17%. Found:
C, 75.10; H, 8.80; Si, 4.09%.
4.1.9. (E)-1-Iodohept-1-ene (15). Anhydrous CrCl2
(22.09 g, 179.71 mmol) is suspended in THF (150 mL) under
argon atmosphere. A solution of hexanaldehyde (3.0 g,
29.95 mmol) and iodoform (23.58 g, 59.90 mmol) in THF
(30 mL) is added dropwise to the suspension at 0 ꢁC. After
stirring at 0 ꢁC for 3 h, the reaction mixture is poured into
water (100 mL) and extracted with ether (3ꢂ100 mL). The
combined organic extracts were dried (Na2SO4) and concen-
trated. Silica gel column chromatography of the crude prod-
uct using petroleum ether/EtOAc (9.5:0.5) as eluent gave 15
(5.90 g, 88%) with E/Z¼95:5 selectivity as a pale yellow oil.
1H NMR (200 MHz, CDCl3): d¼0.92 (t, J¼7.1 Hz, 3H),
1.26–1.43 (m, 6H), 1.62 (q, J¼7.4 Hz, 1H), 2.00–2.18 (m,
1H), 6.01 (d, J¼15.4 Hz, 1H), 6.44–6.59 (m, 1H); 13C
NMR (50 MHz, CDCl3): d¼14.1, 22.9, 28.5, 32.1, 34.4,
141.2, 82.1. Anal. Calcd for C7H13I (224.08): C, 37.52; H,
5.85; I, 56.63%. Found: C, 37.81; H, 5.72; I, 56.56%.
4.1.12. (9S,12S,13S,E)-9-(tert-Butyldiphenylsilyloxy)-
octadec-10-ene-1,12,13-triol (18). To the blue solution pre-
pared by addition of lithium metal (334 mg, 48.18 mmol) to
liquid NH3 (5 mL) was added a solution of 17 (450 mg,
0.668 mmol) in dry THF (5 mL) at ꢀ78 ꢁC. After the mix-
ture was stirred for 1 h, the reaction was quenched by addi-
tion of 2.68 g (50.14 mmol) of NH4Cl. After removal of NH3
by a stream of N2, the mixture was diluted with 50 mL of
CHCl3 and washed with water. The organic layer was dried
(Na2SO4) and concentrated. Silica gel column chromato-
graphy of the crude product using petroleum ether/EtOAc
(4:6) as eluent gave the triol 18 (333 mg, 90%) as a colourless
syrupy liquid. [a]D25 9.3 (c 0.42, CHCl3); IR (CHCl3): nmax
4.1.10. ((S,E)-1-(4-Methoxybenzyloxy)octadec-12-en-10-
yn-9-yloxy) (tert-butyl)diphenylsilane (16). To a stirred
mixture of Pd(PPh3)2Cl2 (181 mg, 0.257 mmol), CuI
(147 mg, 0.77 mmol) in Et3N (2 mL) were added solutions
of (E)-1-iodohept-1-ene 15 (982 mg, 4.38 mmol) in Et3N
(2 mL) and acetylene 14 (1.2 g, 3.94 mmol) in Et3N
(2 mL) under argon. After 6 h, the reaction mixture was
3376, 1644, 1367, 1310, 1178, 1128, 1045, 980, 721 cmꢀ1
;

7630
S. V. Naidu et al. / Tetrahedron 63 (2007) 7624–7633
1H NMR (200 MHz, CDCl3): d¼0.87 (t, J¼6.3 Hz, 3H),
1.04 (s, 9H), 1.4 (br s, 18H), 1.51–1.72 (m, 4H), 2.35 (br s,
2H), 3.38–3.48 (m, 1H), 3.61 (t, J¼6.6 Hz, 2H), 3.94 (t,
J¼5.9 Hz, 1H), 4.08 (q, J¼6.6 Hz, 1H), 5.67 (dd, J¼15.5,
5.9 Hz, 1H), 5.86 (dd, J¼15.5, 5.6 Hz, 1H), 7.36–7.43 (m,
6H), 7.66–7.75 (m, 4H); 13C NMR (50 MHz, CDCl3):
d¼14.0, 22.6, 25.0, 26.1, 26.9, 28.1, 27.0, 28.1, 28.9, 29.1,
29.2, 31.8, 32.8, 32.9, 55.1, 64.1, 72.1, 74.6, 75.3, 127.5,
134.0, 134.8, 135.8, 136.1, 137.8. Anal. Calcd for
C34H54O4Si (554.88): C, 73.60; H, 9.81; Si, 5.06%. Found:
C, 73.8; H, 9.64; Si, 5.33%.
reaction mixture stirred overnight at the same temperature.
The mixture was filtered through a Celite pad and washed
with MeOH and concentrated. The crude product was redis-
solved in CH2Cl2 and washed with saturated aqueous
NaHCO3 and brine, dried (Na2SO4) and concentrated. Silica
gel column chromatography of the crude product using
CHCl3/MeOH (10:1) furnished the target compound pinellic
acid (ꢀ)-1 (28 mg, 78%) as a white solid. Rf¼0.24 (silica gel,
CHCl3/MeOH/AcOH¼10:1:0.1). Mp: 104–106 ꢁC (lit.17a
mp: 104–106 ꢁC); [a]D25 ꢀ7.9 (c 0.30, MeOH) (lit.17a [a]D25
ꢀ8.1 (c 0.32, MeOH)); 1H NMR (200 MHz, CDCl3):
d¼0.89 (t, J¼6.3 Hz, 3H), 1.45–1.25 (m, 16H), 1.50–1.62
(m, 4H), 2.27 (t, J¼7.6 Hz, 2H), 3.41 (m, 1H), 3.91 (dd,
J¼5.5, 5.0 Hz, 1H), 4.05 (m, 1H), 5.65 (dd, J¼15.6, 5.2 Hz,
1H), 5.72 (dd, J¼15.6, 5.1 Hz, 1H); 13C NMR (50 MHz,
CDCl3): d¼177.6, 136.6, 131.2, 76.4, 75.8, 73.0, 38.3,
35.1, 33.6, 33.2, 30.5, 30.4, 30.1, 26.6, 26.5, 26.1, 23.7, 13.9.
4.1.13. (S,E)-9-(tert-Butyldiphenylsilyloxy)-11-((4S,5S)-
2,2-dimethyl-5-pentyl-1,3-dioxolan-4-yl)undec-10-en-1-
ol (19). Compound 19 was prepared following the procedure
described for compound 10 in 92% yield as a colourless
1
liquid. [a]2D5 16.1 (c 0.57, CHCl3); H NMR (200 MHz,
CDCl3): d¼0.90 (t, J¼6.3 Hz, 3H), 1.07 (s, 9H), 1.19–1.39
(br s, 18H), 1.41 (s, 3H), 1.45 (s, 3H), 1.54–1.73 (m, 4H),
2.31 (br s, 1H), 3.64 (t, J¼6.6 Hz, 2H), 4.09 (q, J¼6.6 Hz,
1H), 4.14–4.20 (m, 2H), 5.65 (dd, J¼15.5, 7.1 Hz, 1H), 5.85
(dd, J¼15.5, 5.7 Hz, 1H), 7.36–7.43 (m, 6H), 7.69–7.78 (m,
4H); 13C NMR (50 MHz, CDCl3): d¼14.0, 19.3, 22.5, 24.9,
26.1, 26.9, 28.3, 29.2, 29.4, 29.7, 31.2, 31.9, 32.6, 64.1, 71.7,
80.1, 81.9, 108.6, 127.4, 134.0, 134.8, 135.8, 136.1, 137.8.
Anal. Calcd for C37H58O4Si (594.94): C, 74.70; H, 9.83;
Si, 4.72%. Found: C, 75.01; H, 9.65; Si, 4.87%.
4.1.16. (S,E)-1-(4-Methoxybenzyloxy)octadec-12-en-10-
yn-9-ol (21). To a stirred mixture of Pd(PPh3)2Cl2 (276 mg,
0.39 mmol), CuI (225 mg, 1.18 mmol) in Et3N (2 mL)
were added solutions of (E)-1-iodohept-1-ene 15 (1.50 g,
6.70 mmol) in Et3N (2 mL) and acetylene 13 (1.2 g,
3.94 mmol) in Et3N (2 mL) under argon. After 8 h, the reac-
tion mixture was filtered through Celite and the filtrate was
concentrated. Silica gel column chromatography of the
crude product using petroleum ether/EtOAc (9:1) as eluent
gave 21 (1.36 g, 86%) as a pale yellow oil. [a]2D5 1.75 (c
0.8, CHCl3); IR (CHCl3): n¼3440, 2938, 2864, 1736,
4.1.14. (S,E)-9-(tert-Butyldiphenylsilyloxy)-11-((4S,5S)-
2,2-dimethyl-5-pentyl-1,3-dioxolan-4-yl)undec-10-enoic
acid (20). To a solution of 19 (212 mg, 0.356 mmol) in
EtOAc (5 mL) in 25 mL R.B. flask was added IBX (299 mg,
1.069 mmol) in one portion and the reaction mixture was
refluxed for 5 h. The reaction mixture was filtered through
a pad of Celite and the filtrate was concentrated to give the
crude aldehyde, which was used in the next step without
further purification.
1
1612, 1513, 1248, 1130, 1032 cmꢀ1; H NMR (200 MHz,
CDCl3): d¼0.89 (t, J¼6.7 Hz, 3H), 1.20–1.52 (m, 16H),
1.53–1.75 (m, 4H), 2.01–2.20 (m, 2H), 3.44 (t, J¼6.6 Hz,
2H), 3.81 (s, 3H), 4.12–4.26 (m, 1H), 4.44 (s, 2H), 5.52
(dd, J¼15.9, 1.64 Hz, 1H), 6.07–6.26 (m, 1H), 6.90 (d,
J¼8.7 Hz, 2H), 7.29 (d, J¼8.7 Hz, 2H); 13C NMR (50 MHz,
CDCl3): d¼14.0, 22.5, 25.4, 25.6, 25.7, 28.3, 29.2, 29.4,
29.7, 31.2, 32.9, 38.4, 55.2, 64.4, 70.2, 72.5, 83.7, 89.2,
109.1, 113.7, 129.1, 130.9, 144.4, 159.1. Anal. Calcd for
C26H40O3 (400.59): C, 77.95; H, 10.06%. Found: C, 78.21;
H, 10.11%.
A solution of 79% NaClO2 (48 mg, 0.53 mmol) in 1.0 mL of
water was added dropwise to a stirred solution of the above
crude aldehyde (210 mg, 0.354 mmol) in 0.5 mL of DMSO
and NaH2PO4 (84 mg, 0.71 mmol) in 1.0 mL of water in
5 min at room temperature. The mixture was left overnight
at room temperature and then 5% aqueous solution of
NaHCO3 was added. The aqueous phase was extracted three
times with CH2Cl2 and washed with brine, dried (Na2SO4)
and concentrated to give the acid 20 (81%, 174 mg) as a
yellowish liquid. [a]2D5 ꢀ9.3 (c 0.43, CHCl3); 1H NMR
(200 MHz, CDCl3): d¼0.89 (3H, t, J¼6.3 Hz), 1.07 (s,
9H), 1.19–1.39 (br s, 16H), 1.41 (s, 3H), 1.45 (s, 3H),
1.50–1.62 (m, 4H), 2.26 (t, 2H, J¼7.6 Hz), 3.41 (m, 1H),
4.12–4.16 (m, 2H), 5.66 (dd, 1H, J¼15.6, 5.2 Hz), 5.71
(dd, 1H, J¼15.6, 5.1 Hz), 7.36–7.43 (m, 6H), 7.69–7.78
(m, 4H); 13C NMR (50 MHz, CDCl3): d¼177.6, 137.8,
136.1, 135.8, 134.8, 131.3, 134.0, 127.4, 108.6, 82.1, 80.3,
71.7, 38.8, 32.6, 31.9, 31.2, 29.7, 29.4, 29.2, 28.3, 26.9,
26.1, 24.9, 22.5, 19.3, 14.0. Anal. Calcd for C37H56O5Si
(608.92): C, 72.98; H, 9.27%. Found: C, 73.10; H, 9.38%.
4.1.17. (S,10E,12E)-1-(4-Methoxybenzyloxy)-octadeca-
10,12-dien-9-ol (22). To a suspension of lithium aluminium
hydride (61 mg, 1.62 mmol) in THF (40 mL) was added a
solution of 21 (650 mg, 1.62 mmol) in THF (40 mL) at
0 ꢁC. The mixture was warmed to room temperature and
was stirred for 10 min. The mixture was refluxed for 1 h
and then cooled to 0 ꢁC. The reaction was quenched with
saturated aqueous potassium sodium tartrate solution. After
the suspension was stirred vigorously, the aqueous layer
was extracted with ether. The ethereal extract was washed
with brine, dried (Na2SO4) and concentrated. Silica gel
column chromatography of the crude product using petro-
leum ether/EtOAc (9:1) as eluent gave 22 (542 mg, 83%)
as a pale yellow oil. [a]2D5 3.1 (c 0.4, CHCl3); IR (CHCl3):
n¼3400, 2938, 2863, 1612, 1513, 1457, 1216, 1054, 990;
1H NMR (200 MHz, CDCl3): d¼0.89 (t, J¼6.7 Hz, 3H),
1.20–1.50 (m, 16H), 1.53–1.76 (m, 4H), 2.08 (q, J¼6.8 Hz,
2H), 3.44 (t, J¼6.6 Hz, 2H), 3.80 (s, 3H), 4.05–4.24 (m, 1H),
4.45 (s, 2H), 5.53 (dd, J¼15.9, 6.5 Hz, 1H), 5.71 (m, 1H),
6.01 (dd, J¼15.1, 6.6 Hz, 1H), 6.15 (dd, J¼15.2, 10.5 Hz,
1H), 6.90 (d, J¼8.7 Hz, 2H), 7.29 (d, J¼8.7 Hz, 2H); 13C
NMR (50 MHz, CDCl3): d¼13.8, 22.5, 25.4, 25.7, 28.9,
4.1.15. (9S,12S,13S)-(E)-9,12,13-Trihydroxy-10-octa-
decenoic acid [(L)-pinellic acid 1]. To a stirred solution
of compound 20 (66 mg, 0.108 mmol) in MeOH was added
a catalytic amount of concd HCl at room temperature and the

S. V. Naidu et al. / Tetrahedron 63 (2007) 7624–7633
7631
29.3, 29.4, 29.5, 31.4, 32.6, 32.8, 37.3, 55.0, 72.9, 73.1,
113.5, 129.1, 129.5, 130.1, 131.0, 133.6, 135.8, 158.8.
Anal. Calcd for C26H42O3 (400.59); C, 77.56; H, 10.51%.
Found: C, 77.62; H, 10.33%.
1.61 mmol) was added slowly and stirred for 30 min allow-
ing the reaction mixture to warm to room temperature. The
reaction mixture was poured into water (50 mL) and the
organic layer was separated. The aqueous layer was extracted
with CH2Cl2 (2ꢂ25 mL) and combined organic layers were
washed with water (3ꢂ20 mL), brine (20 mL), dried
(Na2SO4) and passed through short pad of silica gel. The
filtrate was concentrated to give the aldehyde (302 mg) as
pale yellow syrup, which was used as such for the next
step without further purification.
4.1.18. ((S,10E,12E)-1-(4-Methoxybenzyloxy)-octadeca-
10,12-dien-9-yloxy) (tert-butyl)diphenylsilane (23). Com-
pound 23 was prepared following the procedure described
for compound 14 in 96% yield as a colourless liquid. [a]D25
+19.5 (c 0.7, CHCl3); IR (CHCl3): n¼2938, 2864, 1736,
1
1612, 1513, 1248, 1130, 1032 cmꢀ1; H NMR (200 MHz,
CDCl3): d¼0.89 (t, J¼6.7 Hz, 3H), 1.04 (s, 9H), 1.19–1.50
(m, 16H), 1.53–1.81 (m, 4H), 2.07 (q, J¼7.0 Hz, 2H), 3.45
(t, J¼6.6 Hz, 2H), 3.81 (s, 3H), 4.10 (q, J¼6.8 Hz, 1H),
4.44 (s, 2H), 5.56 (dd, J¼15.2, 6.6 Hz, 1H), 5.70 (m, 1H),
6.01 (dd, J¼15.1, 6.8 Hz, 1H), 6.16 (dd, J¼15.2, 10.5 Hz,
1H), 6.89 (d, J¼8.7 Hz, 2H), 7.29 (d, J¼8.7 Hz, 2H), 7.36–
7.46 (m, 6H), 7.64–7.79 (m, 4H); 13C NMR (50 MHz,
CDCl3): d¼13.9, 19.2, 22.5, 25.7, 25.8, 26.9, 28.9, 29.2,
29.5, 29.7, 31.4, 32.5, 32.7, 37.9, 54.9, 64.3, 70.3, 72.5,
113.8, 127.5, 127.6, 127.7, 129.1, 129.4, 129.5, 129.6, 130.1,
131.1, 133.4, 134.0, 135.7, 135.9, 159.0. Anal. Calcd for
C42H60O3Si (641.01): C, 78.70; H, 9.43; Si, 4.38%. Found:
C, 78.88; H, 9.29; Si, 4.51%.
A solution of 79% NaClO2 (68 mg, 0. 60 mmol) in 1.0 mL
of water was added dropwise to a stirred solution of crude
aldehyde (209 mg, 0.40 mmol) in 0.5 mL of DMSO and
NaH2PO4 (97 mg, 0.81 mmol) in 1.0 mL of water in 5 min
at room temperature. The mixture was left overnight at
room temperature and then 5% aqueous solution of NaHCO3
was added. The aqueous phase was extracted three times
with CH2Cl2 and washed with brine, dried (Na2SO4) and
concentrated to give the crude product 25, which was used
as such for the next step without further purification.
The above crude acid 25 (215 mg, 0.40 mmol) was dissolved
in THF (5 mL), followed by the dropwise addition of TBAF
(0.80 mL, 1 M solution in THF, 0.80 mmol). The reaction
mixture was stirred at room temperature overnight and
then quenched by addition of water, and the aqueous layer
was extracted with EtOAc (3ꢂ30 mL) and combined EtOAc
extracts were washed with brine, dried (Na2SO4) and con-
centrated. Silica gel column chromatography of the crude
product using petroleum ether/EtOAc (9:1) as eluent gave
b-dimorphecolic acid (2) (82 mg, 69% yield over three
steps) as a cream-coloured solid. Mp 38–40 ꢁC (lit.19 39–
40 ꢁC); [a]2D5 +15.1 (c 0.8, in MeOH) [lit.19 [a]2D5 +15.4
(c 5.0, in MeOH)]; IR (KBr): n¼3422, 2924, 2869, 1712,
1459, 1321, 1211, 986 cmꢀ1; 1H NMR (200 MHz, CD3OD):
d¼0.89 (t, J¼6.8 Hz, 3H), 1.19–1.51 (m, 16H), 1.53–1.81
(m, 4H), 2.06 (q, J¼7.0 Hz, 2H), 2.24 (t, J¼7.5 Hz, 2H),
4.02 (q, J¼6.6 Hz, 1H), 5.51 (dd, J¼15.1, 6.5 Hz, 1H),
5.66 (m, 1H), 6.02 (dd, J¼15.1, 10.5 Hz, 1H), 6.14 (dd,
J¼15.1, 10.5 Hz, 1H); 13C NMR (50 MHz, CDCl3):
d¼14.0, 22.5, 24.9, 25.3, 28.9, 29.1, 29.3, 29.7, 31.4, 32.6,
34.1, 37.2, 72.8, 129.4, 131.0, 133.5, 135.6, 178.5.
4.1.19. (S,10E,12E)-9-(tert-Butyldiphenylsilyloxy)-octa-
deca-10,12-dien-1-ol (24). To a stirring solution of PMB
ether 22 (380 mg, 0.59 mmol) in CH2Cl2/H2O (10 mL/
0.5 mL, 20:1) was added DDQ (161 mg, 0.71 mmol). The
resulting mixture was stirred for 45 min at room temperature.
The mixture was poured into saturated aqueous NaHCO3 and
further diluted with CH2Cl2. The layers were separated and
the aqueous layer was extracted with CH2Cl2 (2ꢂ10 mL).
The combined organic layers were dried (Na2SO4), filtered
and concentrated. The residue was then filtered through
a pad of Celite and washed with 50% EtOAc/hexane
(20 mL). The solvents were removed under reduced pressure
to give the crude product mixture as yellow oil. Silica gel col-
umn chromatography of the crude product using petroleum
ether/EtOAc (7:3) as eluent gave 24 (275 mg, 89%) as a col-
ourless oil. [a]2D5 +6.28 (c 0.9, CHCl3); IR (CHCl3): n¼3400,
2928, 2855, 1659, 1589, 1464, 1427, 1389, 1216, 1112,
986 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d¼0.89 (t,
J¼6.7 Hz, 3H), 1.04 (s, 9H), 1.19–1.50 (m, 16H), 1.53–1.81
(m, 4H), 2.08 (q, J¼7.0 Hz, 2H), 3.64 (t, J¼6.6 Hz, 2H),
4.12 (q, J¼6.6 Hz, 1H), 5.56 (dd, J¼15.2, 6.6 Hz, 1H), 5.70
(dt, J¼15.2, 7.1 Hz, 1H), 6.02 (dd, J¼15.1, 10.5 Hz, 1H),
6.16 (dd, J¼15.2, 10.4 Hz, 1H), 7.36–7.45 (m, 6H), 7.66–
7.78 (m, 4H); 13C NMR (50 MHz, CDCl3): d¼14.1, 19.2,
22.5, 25.6, 25.8, 26.9, 28.8, 29.5, 29.7, 31.5, 32.6, 32.7,
37.4, 64.1, 73.1, 127.6, 129.4, 129.5, 131.1, 133.6, 134.3,
135.7. Anal. Calcd for C34H52O2Si (520.86): C, 78.40; H,
10.06; Si, 5.39%. Found: C, 78.61; H, 9.87; Si, 5.52%.
4.1.21. ((S,E)-11-(4-Methoxybenzyloxy)-1-(tributyl-stan-
nyl)undec-1-en-3-yloxy) (tert-butyl)diphenylsilane (26).
To a stirred solution of 14 (1.80 g, 3.32 mmol) in benzene
(30 mL) were added n-Bu3SnH (1.1 mL, 3.98 mmol) and
AIBN (catalytic) at room temperature under N2. The reaction
mixture was gently refluxed with stirring for 4 h. The solvent
was removed and the residue was purified by silica gel col-
umn chromatography using petroleum ether/EtOAc (9:1) as
eluent to give 26 (2.74 g, 99%) as yellowish oil. [a]2D5 ꢀ9.8
(c 0.64, CHCl3); IR (CHCl3): n¼3004, 2957, 2928, 2853,
1612, 1513, 1464, 1378, 1247, 1173, 1036 cmꢀ1; 1H NMR
(200 MHz, CDCl3): d¼0.88–0.93 (m, 9H), 1.10 (s, 9H),
1.24 (br s, 10H), 1.26–1.31 (m, 10H), 1.42–1.74 (m, 12H),
3.44 (t, J¼6.6 Hz, 2H), 3.82 (s, 3H), 4.12 (q, J¼6.6 Hz,
1H), 4.45 (s, 2H), 5.95 (dd, J¼19.0, 5.1 Hz, 1H), 6.36 (d,
J¼19.0 Hz, 1H), 6.92 (d, J¼8.7 Hz, 2H), 7.31 (d, J¼8.6 Hz,
2H), 7.37–7.45 (m, 6H), 7.64–7.79 (m, 4H); 13C NMR
(50 MHz, CDCl3): d¼8.9, 9.4, 10.2, 10.6, 11.2, 13.5, 19.3,
24.2, 24.5, 26.1, 26.4, 26.9, 28.9, 29.3, 29.3, 29.7, 37.2,
4.1.20. (9S,10E,12Z)-9-Hydroxy-10,12-octadecadienoic
acid [b-dimorphecolic acid] (2). To a solution of oxalyl
chloride (76 mg, 0.05 mL, 0.60 mmol) in dry CH2Cl2
(20 mL) at ꢀ78 ꢁC was added dropwise dry DMSO
(94 mg, 0.095 mL, 1.90 mmol) in CH2Cl2 (5 mL). After
30 min, alcohol 24 (210 mg, 0.40 mmol) in CH2Cl2 (5 mL)
was added over 10 min giving a copious white precipitate.
After stirring for 1 h at ꢀ78 ꢁC the reaction mixture was
brought to ꢀ60 ꢁC and Et3N (0.163 g, 0.22 mL,

7632
S. V. Naidu et al. / Tetrahedron 63 (2007) 7624–7633
38.1, 55.2, 61.8, 69.9, 72.3, 113.6, 117.0, 127.2, 127.3,
127.4, 129.2, 129.5, 129.56, 129.65, 129.7, 130.8, 133.9,
134.5, 134.9, 135.7, 135.9, 144.9, 159.1. Anal. Calcd for
C47H74O3SiSn (833.88): C, 67.70; H, 8.94; Si, 3.37%.
Found: C, 67.59; H, 9.21; Si, 3.62%.
J¼6.9 Hz, 1H), 4.41 (s, 2H), 5.49 (dt, J¼11.0, 7.1 Hz,
1H), 5.64 (dd, J¼15.0, 7.0 Hz, 1H), 6.01 (dd, J¼11.0,
11.0 Hz, 1H), 6.51 (dd, J¼15.1, 11.0 Hz, 1H), 6.90 (d,
J¼8.7 Hz, 2H), 7.30 (d, J¼8.7 Hz, 2H), 7.36–7.48 (m,
6H), 7.66–7.79 (m, 4H); 13C NMR (50 MHz, CDCl3):
d¼13.9, 19.2, 22.5, 25.7, 25.8, 26.9, 28.9, 29.2, 29.5, 29.7,
31.4, 32.5, 32.7, 37.9, 54.9, 64.9, 70.5, 72.3, 113.8, 113.8,
126.1, 127.5, 127.6, 127.9, 129.1, 129.4, 129.5, 129.6,
130.1, 131.1, 133.4, 134.0, 135.7, 135.9, 159.0. Anal. Calcd
for C42H60O3Si (641.01): C, 78.70; H, 9.43; Si, 4.38%.
Found: C, 78.84; H, 9.28; Si, 4.41%.
4.1.22. ((S,E)-11-(4-Methoxybenzyloxy)-1-iodoundec-1-
en-3-yloxy) (tert-butyl)diphenylsilane (27). To a cooled
(0 ꢁC), stirred solution of 26 (1.60 g, 1.92 mmol) in
CH2Cl2 (40 mL) was added iodine (973 mg, 3.84 mmol).
After 30 min at 0 ꢁC, the reaction mixture was diluted
with CH2Cl2, washed with saturated Na2S2O3 and 10% KF
solutions, and brine. The organic layer was dried (Na2SO4),
filtered and concentrated. Silica gel column chromatography
of the crude product using petroleum ether/EtOAc (9.5:0.5)
as eluent gave 27 (1.24 g, 96%) as a yellowish oil. [a]D25
ꢀ6.1 (c 0.48, CHCl3); IR (CHCl3): n¼2948, 2933, 2861,
4.1.25. (S,10E,12Z)-9-(tert-Butyldiphenylsilyloxy)-octa-
deca-10,12-dien-1-ol (31). Compound 31 was prepared fol-
lowing the procedure described for compound 25 in 94%
yield as a colourless liquid. [a]2D5 +10.1 (c 0.39, CHCl3); IR
(CHCl3): n¼3400, 2928, 2855, 1659, 1589, 1464, 1427,
1389, 1216, 1112, 986, 950, 985 cmꢀ1; 1H NMR (200 MHz,
CDCl3): d¼0.89 (t, J¼6.7 Hz, 3H), 1.05 (s, 9H), 1.19–1.52
(m, 16H), 1.53–1.79 (m, 4H), 2.21 (q, J¼7.0 Hz, 2H), 3.68
(t, J¼6.6 Hz, 2H), 4.07 (q, J¼7.1 Hz, 1H), 5.56 (dd,
J¼15.2, 6.6 Hz, 1H), 5.70 (m, 2H), 6.02 (dd, J¼15.1,
10.5 Hz, 1H), 7.36–7.45 (m, 6H), 7.66–7.78 (m, 4H); 13C
NMR (50 MHz, CDCl3): d¼14.1, 19.2, 22.9, 25.7, 25.8,
26.9, 28.8, 29.5, 29.7, 31.4, 32.6, 32.7, 37.8, 64.4, 73.1,
126.3, 127.6, 127.9, 129.4, 129.5, 133.2, 134.1, 135.7.
Anal. Calcd for C34H52O2Si (520.86): C, 78.40; H, 10.06;
6.14; Si, 5.39%. Found: C, 78.53; H, 10.28; Si, 5.58%.
1
1612, 1515, 1465, 1372, 1174, 1092, 948 cmꢀ1; H NMR
(200 MHz, CDCl3): d¼1.10 (s, 9H), 1.24 (br s, 10H), 1.53–
1.72 (m, 4H), 3.47 (t, J¼6.1 Hz, 2H), 3.92 (s, 3H), 4.12 (q,
J¼6.6 Hz, 1H), 4.45 (s, 2H), 6.29 (m, 2H), 6.53 (d,
J¼8.7 Hz, 2H), 7.31 (d, J¼8.6 Hz, 2H), 7.37–7.45 (m, 6H),
7.64–7.79 (m, 4H); 13C NMR (50 MHz, CDCl3): d¼19.2,
24.3, 24.5, 26.1, 26.5, 26.8, 28.9, 29.25, 29.28, 29.65, 37.2,
38.1, 55.0, 62.8, 70.1, 72.2, 114.0, 117.0, 127.2, 127.3,
127.4, 128.6, 129.5, 129.6, 129.7, 130.8, 133.9, 134.5, 134.9,
135.7, 135.9, 147.6, 161.4. Anal. Calcd for C35H47IO3Si
(670.74): C, 62.67; H, 7.06; I, 18.92%. Found: C, 62.89; H,
6.96; I, 19.24%.
4.1.26. a-Dimorphecolic acid (3). Compound 3 was pre-
pared following the procedure described for compound 2
in 89% yield as a yellow syrup. [a]2D5 +11.4 (c 0.4, in
4.1.23. ((S,E)-1-(4-Methoxybenzyloxy)octadec-10-en-12-
yn-9-yloxy) (tert-butyl)diphenylsilane (29). Compound
29 was prepared following the procedure described for
compound 21 in 89% yield as a pale yellow oil. [a]D25
ꢀ15.4 (c 0.4, CHCl3); IR (CHCl3): n¼3004, 2957, 2928,
2853, 1612, 1513, 1464, 1378, 1247, 1173, 1036 cmꢀ1; 1H
NMR (200 MHz, CDCl3): d¼0.89 (t, J¼6.7 Hz, 3H), 1.04
(s, 9H), 1.20–1.52 (m, 16H), 1.53–1.81 (m, 4H), 2.08 (q,
J¼6.8 Hz, 2H), 3.49 (t, J¼6.6 Hz, 2H), 3.81 (s, 3H), 4.14–
4.28 (m, 1H), 4.44 (s, 2H), 5.72 (dd, J¼15.9, 1.64 Hz, 1H),
6.03–6.24 (m, 1H), 6.91 (d, J¼8.7 Hz, 2H), 7.29 (d, J¼
8.7 Hz, 2H), 7.36–7.45 (m, 6H), 7.66–7.78 (m, 4H); 13C
NMR (50 MHz, CDCl3): d¼14.0, 19.2, 22.6, 25.7, 25.8, 26.9,
28.9, 29.2, 29.5, 29.7, 31.4, 32.5, 32.7, 37.9, 55.1, 64.6, 71.3,
72.5, 81.8, 82.4, 113.8, 127.5, 127.6, 127.7, 129.0, 129.4,
129.6, 130.5, 132.5, 133.8, 134.0, 135.7, 135.9, 159.1. Anal.
Calcd for C42H58O3Si (638.99): C, 78.94; H, 9.15; Si,
4.40%. Found: C, 79.22; H, 9.01; Si, 4.67%.
MeOH); IR (KBr): n¼3600, 1715, 950, 985 cmꢀ1
;
1H
NMR (200 MHz, CD3OD): d¼0.90 (t, J¼6.7 Hz, 3H),
1.19–1.50 (m, 16H), 1.52–1.79 (m, 4H), 2.20 (m, 2H),
2.36 (t, J¼7.0 Hz, 2H), 4.17 (q, J¼7.0 Hz, 1H), 5.47 (dt,
J¼11.0, 7.1 Hz, 1H), 5.66 (dd, J¼15.0, 7.0 Hz, 1H), 5.98
(dd, J¼11.0, 11.0 Hz, 1H), 6.51 (dd, J¼15.1, 11.0 Hz,
1H); 13C NMR (50 MHz, CD3OD): d¼14.1, 22.5, 25.6,
25.8, 26.9, 28.8, 29.5, 29.7, 31.5, 32.6, 32.7, 37.4, 73.0,
126.2, 127.9, 133.2, 135.9, 178.6.
Acknowledgements
S.V.N. and P.G. thank CSIR and UGC New Delhi for finan-
cial assistance. We are grateful to Dr. M. K. Gurjar for his
support and encouragement. The financial support from
DST, New Delhi (Grant No. SR/S1/OC-40/2003) is grate-
fully acknowledged. This is NCL communication no. 6702.
4.1.24. ((S,10E,12Z)-1-(4-Methoxybenzyloxy)-octadeca-
10,12-dien-9-yloxy) (tert-butyl)diphenylsilane (30). To
a solution of 29 (620 mg, 0.97 mmol) in 10 mL of ethyl
acetate/pyridine/1-octene (10:1:1) was added Lindlar’s cata-
lyst (20 mg). The reaction mixture was stirred for 6 h under
a balloon of H2 at room temperature and filtered through
a Celite pad. The filtrate was concentrated and the residue
was purified by silica gel column chromatography using
petroleum ether/EtOAc (9:1) as eluent to give 30 (590 mg,
95%) as a pale yellow oil. [a]2D5 +12.59 (c 0.43, CHCl3);
References and notes
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