Total synthesis of the Z-isomers of nonenolide and desmethyl nonenolide

Article abstract of DOI:10.1016/j.tetasy.2009.05.002

RCM and Yamaguchi esterification reactions were used as the key steps for the stereoselective total synthesis of Z-isomers of nonenolide and desmethyl nonenolide.

Full text of DOI:10.1016/j.tetasy.2009.05.002

Tetrahedron: Asymmetry 20 (2009) 1330–1336
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Tetrahedron: Asymmetry
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Total synthesis of the Z-isomers of nonenolide and desmethyl nonenolide
*
Gowravaram Sabitha , P. Padmaja, K. Sudhakar, J. S. Yadav
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
RCM and Yamaguchi esterification reactions were used as the key steps for the stereoselective total
synthesis of Z-isomers of nonenolide and desmethyl nonenolide.
Ó 2009 Published by Elsevier Ltd.
Received 27 April 2009
Accepted 1 May 2009
Available online 3 June 2009
1. Introduction
Our retrosynthetic analysis is depicted in Scheme 1. Z-Isomers,
3 and 4 could be synthesized by the RCM reaction of 5 and 10,
The ascomycetous genus Cordyceps is a rich source of biologically
active secondary metabolites, such as antimalarial erythostominon-
es,1 antimalarial cordypyridones,2 and antitumor sterols.3 It has also
found extensive use in food and herbal medicines in Asia. However,
reports on the isolation of secondary metabolites from Cordyceps
militaris, an enthomopathogenic fungus belonging to the class of
ascomycetes, have been sparse. Cordycepin (30-deoxyadenosine), a
secondary metabolite previously isolated from C. militaris possesses
antifungal-, antiviral-, and antitumor activities. Nonenolide 1, a
medium-sized macrolide, was recently isolated as a white solid from
C. militaris BCC 2816, and showed antimalarial activity.4 The
structure was elucidated by spectroscopic data and X-ray crystallo-
graphic analysis. In spite of its interesting antimalarial activity, a few
syntheses of 1 have been recently reported.5 In continuation of our
interest on the synthesis of bio-active lactones6 using ring-closing
metathesis (RCM) as a key step, we herein report the synthesis of
Z-isomers 3 and 4 of nonenolide 1 and desmethyl nonenolide 2
(Fig. 1) using RCM reactions. Our strategy involves the esterification
of two appropriately functionalized components under the
Yamaguchi conditions, followed by the Grubb catalyst-mediated
ring-closing metathesis to afford the target compounds.
respectively. These intermediates in turn could be synthesized
from the fragments 6, 7, and 11 via the Yamaguchi esterification.
The common fragment 6 for both targets, could be obtained from
9, fragments 7 and 11 could be derived from the 4-penten-1-ol 8
and commercially available 1,4-butane diol 12, respectively.
2. Results and discussion
The synthesis of acid component 6 began with 13 prepared
from homopropargyl alcohol 9 by a literature procedure.7 The
primary hydroxyl group in 13 was oxidized with Dess–Martin peri-
odinane8 (DMP) to afford the corresponding aldehyde, which
was oxidized to the acid 6 with NaClO2 in the presence of
NaH2PO4ꢀ2H2O and 2-methyl-2-butene9 in 80% yield over two
steps (Scheme 2).
Simultaneously, another intermediate 7 was synthesized from
chiral epoxide 14, prepared from 4-pentene-1-ol 8 following the
literature procedure.10 The reduction of 14 with LAH in THF at rt
for 2 h afforded secondary alcohol 15 in 70% yield. The secondary
alcohol was protected as THP ether 16 with 2,3-dihydropyran in
the presence of PTSA (cat.) in CH2Cl2 followed by removal of the
O
O
O
O
O
O
O
O
OH
OH
OH
OH
OH
OH
OH
OH
1
2
3
4
Figure 1.
* Corresponding author. Tel./fax: +91 40 27160512.
E-mail address: gowravaramsr@yahoo.com (G. Sabitha).
0957-4166/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2009.05.002

G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 1330–1336
1331
OTBS
O
O
OH
O
O
OH
7
8
9
+
OH
OH
O
OTBS
OH
OH
HO
6
3
5
HO
O
OTBS
O
O
HO
O
6
O
+
OH
OTBS
OH
HO
HO
OH
OH
OH
12
11
10
4
Scheme 1. Retrosynthetic analysis.
OTBS
O
OTBS
a, b
ref. 7
HO
HO
HO
6
9
13
Scheme 2. Reagents and conditions: (a) DMP, CH2Cl2, 0 °C to rt, 1 h, 95%; (b) NaClO2, NaH2PO4ꢀ2H2O, 2-methyl-2-butene, t-BuOH, 6 h, 70%.
benzyl group with Pd/C in EtOAc to afford 17 (85%). The primary
hydroxyl was oxidized to the aldehyde under Swern conditions11
and homologated by a two-carbon Wittig ylide, (ethoxycarbonyl-
methylene)triphenyl phosphorane in benzene at reflux for 3 h fur-
With two key fragments 6 and 11 in hand (Scheme 6), the next
concern was to couple them by a Yamaguchi reaction to afford the
diene ester 32. The RCM reaction in 32 was not successful as was
the case with 24 in Scheme 4. The two TBS groups were removed
to give compound 10. Finally, treatment of 10 with Grubbs’ catalyst
II in CH2Cl2 at reflux temperature for 3 h afforded the Z-isomer of
desmethyl nonenolide 4 in 70% yield. The structure and stereochem-
istry were established by 1H and 13C NMR analysis (Scheme 6).
nishing
a,b-unsaturated ester 18 in 90% yield. Ester 18 was
reduced with DIBAL-H in CH2Cl2 at 0 °C to allylic alcohol 19 in
85% yield. Sharpless epoxidation of allylic alcohol 19 with (ꢁ)-
DET, Ti(OiPr)4, and cumene hydroperoxide in dry CH2Cl2 for 5 h
afforded 20 (75%). The epoxy alcohol was converted into the corre-
sponding iodide12 21 with iodine, Ph3P, and imidazole for 1 h
(90%), which on reductive elimination with activated Zn dust13 in
refluxing ethanol for 2 h afforded chiral allylic alcohol 22 (80%).
The secondary hydroxyl was protected as the silyl ether 23 with
TBDMSCl and imidazole and deprotection of the THP group14 with
solid NH4Cl in MeOH at reflux temperature afforded the required
alcohol fragment 7 (70%) (Scheme 3).
3. Conclusions
In conclusion, the total synthesis of the Z-isomers of nonenolide
and desmethyl nonenolide has been accomplished. The highlights
of the synthesis are the utilization of RCM and Yamaguchi cycliza-
tion reactions as the key steps.
Next, we attempted to couple the two fragments in order to con-
struct a 10-membered ring by RCM reaction. Accordingly, the Yam-
aguchi protocol was (DCC and DMAP)15 explored to afford diene
ester 24 in 85% yield (Scheme 4). It is important to note that the
RCM reaction did not proceed when the two hydroxyl groups were
protected as TBS ethers. Therefore, two TBS groups in 24 were
removed using TBAF in THF to afford diol 5 and the ring-closing
metathesis reaction using Grubbs’ second generation catalyst16
was performed in CH2Cl2 at reflux temperature for 3 h to afford the
Z-isomer of nonenolide 3 in 70% yield. The spectroscopic data of syn-
thetic 3 are in good agreement with those reported in the literature.
The synthesis of 11 began with the commercially available 1,4-
butane diol 12 by following the known reactions. Thus, mono
protection (DHP/PTSA/CH2Cl2/rt), Swern oxidation, and homologa-
tion by a two-carbon Wittig ylide, ester reduction, epoxidation,
iodination, and reduction by zinc gave compound 30. Next, the sec-
ondary alcohol was protected as its TBS-ether and THP deprotec-
tion to give the required fragment 11 (Scheme 5).
4. Experimental
4.1. General
Reactions were conducted under N2 in anhydrous solvents such
as CH2Cl2, THF, and EtOAc. All reactions were monitored by TLC
(silica-coated plates and visualizing under UV light). Light petro-
leum ether (bp 60–80 °C) was used. Yields refer to chromatograph-
ically and spectroscopically (1H, 13C NMR) homogeneous material.
Air-sensitive reagents were transferred by syringe or double-ended
needle. Evaporation of solvents was performed at reduced pressure
on a Buchi rotary evaporator. 1H and 13C NMR spectra of samples in
CDCl3 were recorded on Varian FT-200 MHz (Gemini) and Bruker
UXNMR FT-300 MHz (Avance) spectrometers. Chemical shifts (d)
are reported relative to TMS (d = 0.0) as an internal standard. Mass
spectra were recorded E1 conditions at 70 eV on LC–MSD (Agilent
technologies) spectrometers. All high resolution spectra were

1332
G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 1330–1336
To a stirred solution of above aldehyde in t-BuOH/2-methyl 2-bu-
ref.10
b, c
a
8
OBn
R
OBn
OR1
tene (2:1, 6 mL), NaClO2 (0.5 g, 5.55 mmol), and NaH2PO4ꢀ2H2O
(0.86 g, 5.55 mmol) [dissolved in water (2 mL)] were added and stir-
red for 6 h at rt. Solvent was removed under reduced pressure and
extracted with EtOAc (2 ꢂ 5 mL), the combined organic layers were
washedwithbrine(5 mL), anddried(Na2SO4). Thesolventwasevap-
orated and the residue was purified by column chromatography (sil-
ica gel, 60–120 mesh, EtOAc/hexane, 1:9) to afford the acid 6 (0.6 g,
O
OH
15
14
d, e
OR
OTHP
70% yield) as a colorless liquid. ½a D25
ꢃ
¼ þ1:2 (c 1.2, CHCl3); 1H NMR
18 R=COOEt
16 R=THP, R1=Bn
19 R=CH2OH
(200 MHz, CDCl3): 0.01 (d, 6H, J = 3.1 Hz), 0.82 (s, 9H), 2.40–2.51
(m, 2H), 4.50 (q, 1H, J = 6.2 Hz), 4.97–5.10 (d, 1H, J = 10.9 Hz),
5.11–5.28 (d, 1H, J = 17.1 Hz), 5.64–5.91 (m, 1H); 13C NMR
(75 MHz, CDCl3): ꢁ5.2, ꢁ4.4, 25.7, 43.2, 70.6, 115.2, 139.6, 176.2;
IR (neat): 3361, 2926, 2856, 1715 cmꢁ1; HRMS: m/z [M+Na]+ calcd
for C11H22O3SiNa: 253.1235; found: 253.1242.
1
17
R=THP, R =H
O
OR
f, g
h, i
R
OTHP
20 R=OH
OTHP
22 R = H
21 R=I
23 R = TBS
OTBS
4.1.2. (2R)-5-(Benzyloxy)pentan-2-ol 15
To a stirred suspension of LiAlH4 (1.6 g, 45.3 mmol) in dry THF
(10 mL) at 0 °C was added dropwise, a solution of compound 14
(5.8 g, 30.2 mmol) in dry THF (10 mL). The reaction mixture was al-
lowed to warm to rt, and was stirred for 4 h. It was then cooled to
0 °C, diluted with ether, and quenched with dropwise addition of
saturated aqueous Na2SO4 (5 mL). The solid material was filtered
and washed thoroughly with hot ethyl acetate for several times.
The combined organic layers were dried over anhydrous Na2SO4.
The solvent was removed under vacuum and the residue was puri-
fied by silica gel column chromatography to afford the compound
j
OH
7
Scheme 3. Reagents and conditions: (a) LAH, THF, 0 °C to rt, 2 h, 70%; (b) 2,3-
dihydro-2H-pyran, cat. PTSA, CH2Cl2, 0 °C, 2 h; (c) Pd/C, EtOH, 4 h, 85%; (d) (i)
(COCl)2, DMSO, Et3N, CH2Cl2, ꢁ78 °C, 2 h; (ii) Ph3P@CHCOOEt, benzene, reflux, 3 h,
90% (over two steps); (e) DIBAL-H, CH2Cl2, 0 °C to rt, 2 h, 85%; (f) (ꢁ)-DET, Ti(OiPr)4,
cumene hydroperoxide, 4 Å MS, CH2Cl2, ꢁ20 °C, 5 h, 75%; (g) I2, Ph3P, imidazole,
ether/acetonitrile (3:1), 0 °C to rt, 1 h, 90%; (h) activated Zn, EtOH, reflux, 1–2 h 80%;
(i) TBDMSCl, imidazole, DMAP, CH2Cl2, rt, 30 min, 95%; (j) comm. NH4Cl, MeOH,
reflux, 3 h, 65%.
15 (4.6 g, 80%) as a viscous liquid. ½a D25
ꢃ
¼ þ9:0 (c 1.25, CHCl3); 1H
NMR (300 MHz, CDCl3): 1.15–1.24 (d, 3H, J = 6.0 Hz), 1.45–1.81
(m, 4H), 2.36 (s, 1H, OH), 3.47–3.58 (t, 2H, J = 5.2 Hz), 3.72–3.88
(m, 1H), 4.53 (s, 2H), 7.23–7.42 (m, 5H); 13C NMR (75 MHz, CDCl3):
23.4, 26.3, 36.5, 67.7, 70.5, 73.0, 127.6, 127.7, 128.3, 138.1; IR
(neat): 3423, 2926, 2857, 1454, 1365, 1097, 1027, 771, 738,
698 cmꢁ1; HRMS: m/z [M+Na]+ calcd for C12H18O2Na: 217.1204;
found: 217.1211.
recorded on QSTAR XL hybrid ms/ms system (Applied Biosystems/
MDS sciex, foster city, USA), equipped with an ESI source (IICT,
Hyderabad). Column chromatography was performed on silica
gel (60–120 mesh) supplied by Acme Chemical Co., India. TLC
was performed on Merck 60 F-254 silica gel plates. Optical rota-
tions were measured with JASCO DIP-370 Polarimeter at 25 °C.
4.1.1. (3S)-3-{[1-(tert-Butyl)-1,1-dimethylsilyl]oxy}-4-pentenoic
acid 6
4.1.3. 2-{[(1R)-4-(Benzyloxy)-1-methylbutyl]oxy}tetrahydro-
2H-pyran 16
To a stirred solution of 13 (0.84 g, 3.88 mmol) in dry CH2Cl2
(20 mL), NaHCO3 (0.32 g, 3.88 mmol) was added at 0 °C. Dess–Mar-
tin periodinane (1.97 g, 4.65 mmol) was added and the reaction
mixture was stirred at rt for 1 h. The reaction mixture was
quenched with a saturated solution of NaHCO3 and sodium thio-
sulfate (1:7) (5 mL) at 0 °C and extracted with CH2Cl2
(3 ꢂ 10 mL). The organic layer was washed with water (10 mL)
and dried (Na2SO4). The solvent was evaporated and the residue
was used directly for further reaction.
In a 100-mL round-bottomed flask, fitted with a nitrogen adap-
tor, the compound 15 (4.6 g, 23.7 mmol) in dry CH2Cl2 (10 mL) was
taken and catalytic amount of PTSA was added. Then the reaction
mixture was cooled to 0 °C. To this 2H-3,4-dihydropyran (2.4 g,
35.5 mmol) was added dropwise. After completion of addition,
the reaction mixture was allowed to stir for 3 h.
The reaction mixture was diluted with CH2Cl2, and the organic
layer was washed with water, aq NaHCO3, and dried over anhy-
O
O
O
O
O
OH
a
b
HO
+
OH
OTBS
OTBS
OH
OTBS
OTBS
5
c
24
6
7
O
O
O
O
OTBS
OH
OH
OTBS
3
Scheme 4. Reagents and conditions: (a) DCC, DMAP, CH2Cl2, 0 °C to rt, 6 h, 85%; (b) TBAF, THF, 0 °C, 2 h, 70%; (c) Grubbs catalyst II, CH2Cl2, reflux, 3 h, 70%.

G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 1330–1336
1333
THPO
a
b, c
HO
OH
OH
25
12
O
f , g
THPO
d, e
THPO
R
R
26
R=COOEt
28 R=OH
29 R=I
27 R=CH2OH
OR1
OTBS
h
THPO
HO
30 R11=H
11
31
R =TBS
Scheme 5. Reagents and conditions: (a) 2,3-dihydro-2H-pyran, cat. PTSA, CH2Cl2, 0 °C, 2 h; (b) (i) (COCl)2, DMSO, Et3N, CH2Cl2, ꢁ78 °C, 2 h; (ii) Ph3P@CHCOOEt, benzene,
reflux, 3 h, 90% (over two steps); (c) DIBAL-H, CH2Cl2, 0 °C to rt, 2 h, 85%; (d) (ꢁ)-DET, Ti(OiPr)4, cumene hydroperoxide, 4 Å MS, CH2Cl2, ꢁ20 °C, 5 h, 75%; (e) I2, Ph3P,
imidazole, ether/acetonitrile (3:1), 0 °C to rt, 1 h, 90%; (f) activated Zn, EtOH, reflux, 1–2 h 80%; (g) TBDMSCl, imidazole, DMAP, CH2Cl2, rt, 30 min, 95%; (h) comm. NH4Cl,
MeOH, reflux, 3 h, 65%.
O
O
O
O
O
OH
HO
a
b
+
OH
OTBS
OTBS
OH
OTBS
OTBS
32
10
6
11
c
O
O
O
O
OTBS
OH
OTBS
OH
4
Scheme 6. Reagents and conditions: (a) DCC, DMAP, CH2Cl2, 0 °C to rt, 6 h, 85%; (b) TBAF, THF, 0 °C, 2 h, 70%; (c) Grubbs catalyst II, CH2Cl2, reflux, 3 h, 70%.
drous Na2SO4. Concentration under reduced pressure and purifica-
tion over silica gel column chromatography afforded pure tetrahy-
dro pyranyl ether 16 (5.3 g, 81%) as a viscous liquid. 1H NMR
(300 MHz, CDCl3): 1.06–1.24 (dd, 3H, J = 6.0, 6.8 Hz), 1.42–1.91
(m, 10H), 3.39–3.53 (m, 3H), 3.63–3.95 (m, 2H), 4.43–4.51 (d, 2H,
J = 2.2 Hz), 4.52–4.72 (m, 1H), 7.16–7.41 (m, 5H); 13C NMR
(75 MHz, CDCl3): 19.5, 21.4, 25.3, 26.4, 30.6, 34.1, 62.3, 67.5,
70.3, 73.2, 98.8, 127.5, 127.7, 128.4, 138.2; IR (neat): 2937, 2855,
1739, 1453, 1364, 1202, 1117, 1026, 996, 736, 698 cmꢁ1; HRMS:
m/z [M+Na]+ calcd for C17H26O3Na: 301.1779; found: 301.1787.
3416, 2925, 2855, 1630, 1454, 1383, 1120, 1028, 756 cmꢁ1; HRMS:
m/z [M+Na]+ calcd for C10H20O3Na: 211.1310; found: 211.1320.
4.1.5. Ethyl (E,6R)-6-(tetrahydro-2H-2-pyranyloxy)-2-
heptenoate 18
To a stirred solution of oxalyl chloride (4.4 g, 34.68 mmol) in
dry CH2Cl2 (40 mL) at ꢁ78 °C, dry DMSO (5.4 g, 69.2 mmol) was
added dropwise. After 30 min, alcohol 17 (3.26 g, 17.3 mmol) in
CH2Cl2 (20 mL) was added over 10 min giving a copious white pre-
cipitate. After stirring for 2 h at ꢁ78 °C, Et3N (10.5 g, 103.8 mmol)
was added slowly and stirred for 30 min allowing the reaction mix-
ture to warm to rt. The reaction mixture was then diluted with
water (30 mL) and CH2Cl2 (3 ꢂ 40 mL). The combined organic layer
was washed with water (20 mL), brine (20 mL), dried (Na2SO4), and
concentrated in vacuo to afford the aldehyde, which was directly
used for further reaction.
4.1.4. (4R)-4-(Tetrahydro-2H-2-pyranyloxy)pentan-1-ol 17
To a stirred solution of 16 (5.67 g, 0.02 mmol) in EtOAc (20 mL),
10% Pd/C (catalytic) was added under hydrogen atmosphere and
stirred for 4 h. Later, the reaction mixture was filtered through a
pad of Celite and concentrated in vacuo. The crude residue so ob-
tained was purified by column chromatography (silica gel, 60–
120 mesh, EtOAc/hexane, 1:2.3) to afford alcohol 17 (3.06 g, 85%
To a stirred solution of above crude aldehyde in benzene
(60 mL) was added (ethoxycarbonylmethylene)triphenyl phos-
phorane (9 g, 25.95 mmol) at rt. After 3 h, the solvent was evapo-
rated and the residue was purified by column chromatography
(silica gel, 60–120 mesh, EtOAc/hexane, 1:2.3) to afford 18 (3.9 g,
yield) as a brown color liquid. ½a D25
ꢃ
¼ þ19:6 (c 0.65, CHCl3); 1H
NMR (300 MHz, CDCl3): 1.10–1.28 (dd, 3H, J = 6.0, 6.0 Hz), 1.35–
1.92 (m, 10H), 3.30–3.54 (m, 1H), 3.57–3.68 (t, 2H, J = 6.0 Hz),
3.69–3.96 (m, 2H), 4.51–4.70 (m, 1H); 13C NMR (75 MHz, CDCl3):
19.6, 21.4, 25.3, 26.4, 30.6, 33.8, 62.3, 67.4, 73.9, 98.8; IR (neat):
90% yield) as a colorless liquid. ½a D25
ꢃ
¼ þ5:6 (c 1.45, CHCl3); 1H
NMR (300 MHz, CDCl3): 1.08–1.20 (dd, 3H, J = 6.0, 6.0 Hz), 1.21–

1334
G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 1330–1336
1.33 (t, 3H, J = 6.8 Hz), 1.43–1.75 (m, 8H), 2.14–2.46 (m, 2H), 3.40–
3.54 (m, 1H), 3.64–3.95 (m, 2H), 4.09–4.23 (q, 2H, J = 6.8 Hz), 4.51–
4.69 (m, 1H), 5.72–5.86 (m, 1H), 6.84–7.05 (m, 1H); 13C NMR
(75 MHz, CDCl3): 14.3, 19.8, 21.6, 25.5, 30.7, 31.1, 35.6, 60.1,
62.7, 73.4, 98.9, 121.4, 149.0, 166.4; IR (neat): 3455, 2934, 2858,
1720, 1653, 1175, 1028, 989, 769 cmꢁ1; HRMS: m/z [M+Na]+ calcd
for C14H24O4Na: 279.1572; found: 279.1570.
was evaporated and the residue was purified by column chroma-
tography (silica gel, 60–120 mesh, EtOAc/hexane, 1:9) to afford
21 (0.59 g, 90%) as a yellow liquid. 1H NMR (300 MHz, CDCl3):
1.06–1.28 (dd 3H, J = 6.0, 6.0 Hz), 1.38–1.92 (m, 10H), 2.67–2.86
(m, 1H), 2.87–3.10 (m, 2H), 3.19–3.59 (m, 2H), 3.64–4.00 (m,
2H), 4.51–4.74 (m, 1H); 13C NMR (75 MHz, CDCl3): 4.9, 19.6, 21.4,
25.4, 30.7, 31.1, 33.5, 58.2, 58.3, 67.1, 73.5, 98.9; IR (neat): 3451,
2937, 2863, 1451, 1127, 1026, 993, 872 cmꢁ1
; HRMS: m/z
4.1.6. (E,6R)-6-(Tetrahydro-2H-2-pyranyloxy)-2-hepten-1-ol (19)
To a cooled (0 °C) solution of 18 (3.1 g, 12.10 mmol) in dry
CH2Cl2 (40 mL), DIBAL-H (2.58 g, 18.16 mmol, 20% solution in
toluene) was added slowly for 15 min. The reaction mixture was
stirred at rt for 2 h, cooled to 0 °C, and quenched with methanol
(1 mL) and sodium potassium tartarate solution (5 mL). The reac-
tion mixture was passed through a short pad of Celite. The filtrate
was concentrated and the residue was purified by column chro-
matography (silica gel, 60–120 mesh, EtOAc/hexane, 1:2.3) to af-
[M+Na]+ calcd for C12H21O3INa: 363.1223; found: 363.1228.
4.1.9. (3R,6R)-6-(Tetrahydro-2H-2-pyranyloxy)-1-hepten-3-ol 22
To a stirred solution of 21 (0.59 g, 1.75 mmol) in EtOH (20 mL),
activated Zn dust (1.14 g, 17.5 mmol) was added and stirred at
reflux for 1–2 h. The reaction mixture was passed through a short
pad of Celite. The filtrate was concentrated and the residue was puri-
fied by column chromatography silica gel, 60–120 mesh, EtOAc/hex-
ane, 1:4) to afford 22 (0.29 g, 80% yield) as a colorless liquid. 1H NMR
(300 MHz, CDCl3): 1.09–1.27 (dd 3H, J = 6.0, 6.6 Hz), 1.38–1.92 (m,
10H), 3.29–3.53 (m, 1H), 3.64–3.94 (m, 2H), 4.00–4.18 (m, 1H),
4.50–4.71 (m, 1H), 5.01–5.27 (dd, 2H, J = 10.4, 17.1 Hz), 5.75–5.93
(m, 1H); 13C NMR (75 MHz, CDCl3): 19.6, 22.0, 25.4, 30.7, 31.1,
36.7, 62.3, 67.4, 73.0, 98.8, 114.5, 141.2; IR (neat): 3438, 2940,
2866, 1447, 1130, 1074, 1026, 993, 919 cmꢁ1; HRMS: m/z [M+Na]+
calcd for C12H22O3Na: 237.2108; found: 237.2112.
ford 19 (2 g, 85% yield) as a colorless liquid. ½a D25
¼ ꢁ1:4 (c 1.25,
ꢃ
CHCl3); 1H NMR (200 MHz, CDCl3): 1.04–1.28 (dd, 3H, J = 5.8,
6.6 Hz), 1.35–1.76 (m, 8H), 1.98–2.28 (m, 2H), 3.25–3.55 (m, 1H),
3.56–4.00 (m, 2H), 4.01–4.10 (d, 2H, J = 2.9 Hz), 4.50–4.72 (m,
1H), 5.51–5.80 (m, 2H); 13C NMR (75 MHz, CDCl3): 19.7, 21.3,
25.4, 30.6, 31.1, 36.7, 62.5, 63.6, 73.3, 98.7, 129.1, 132.9; IR (neat):
3418, 2938, 2855, 1453, 1134, 1076, 1023, 997, 972, 868 cmꢁ1
;
HRMS: m/z [M+Na]+ calcd for C12H22O3Na: 237.1466; found:
237.1477.
4.1.10. tert-Butyl(dimethyl)({(1R)-1-[(3R)-3-(tetrahydro-2H-2-
pyranyloxy)butyl]-2-propenyl}oxy)silane 23
4.1.7. {(2R,3R)-3-[(3R)-3-(Tetrahydro-2H-2-pyranyloxy)butyl]
oxirane-2-yl}methanol 20
To a stirred solution of 22 (0.29 g, 1.37 mmol) in dry CH2Cl2
(10 mL), imidazole (0.18 g, 2.74 mmol) was added. After 5 min
TBDMSCl (0.31 g, 2.05 mmol) and cat. DMAP were added and stir-
red at rt for 30 min. The solvent mixture was evaporated and the
residue was purified by column chromatography (silica gel, 60–
120 mesh, EtOAc/hexane, 1:24) to afford 23 (0.42 g, 95% yield) as
In a 100-mL two-necked round-bottomed flask, 10 mL of dry
CH2Cl2 was added to 4 Å powdered activated molecular sieves
and suspension mixture was cooled to ꢁ20 °C, Ti(OiPr)4 (0.58 mL,
1.96 mmol) and
D
(ꢁ) DET (0.4 g, 1.96 mmol) in dry CH2Cl2
(10 mL) were added subsequently with stirring and the resulting
mixture was stirred for 30 min at ꢁ25 °C. Compound 19 (2 g,
9.8 mmol) in dry CH2Cl2 (20 mL) was then added and the resulting
mixture was stirred for another 30 min at ꢁ25 °C followed by addi-
tion of cumenehydroperoxide (2.23 mL, 14.7 mmol) and the result-
ing mixture was stirred at the same temperature for 5 h. It was
then warmed to 0 °C, quenched with 1 mL of water, and stirred
for 1 h at rt. After that 30% aqueous NaOH solution saturated with
NaCl (1 mL) was then added and the reaction mixture was stirred
vigorously for another 30 min at rt. The resulting mixture was then
filtered through Celite rinsing with CH2Cl2. The organic phase was
separated and the aqueous phase was extracted with CH2Cl2. Com-
bined organic phases were washed with brine and dried over anhy-
drous Na2SO4. The solvent was removed under reduced pressure
and purified by silica gel column chromatography to afford 20
a colorless liquid. ½a D25
ꢃ
¼ ꢁ0:8 (c 0.75, CHCl3); 1H NMR (300 MHz,
CDCl3): 0.03 (d, 6H, J = 6.4 Hz), 0.89 (s, 9H), 1.05–1.23 (dd, 3H,
J = 6.0, 6.2 Hz), 1.38–1.92 (m, 10H), 3.26–3.51 (m, 1H), 3.61–3.94
(m, 2H), 4.00–4.18 (m, 1H), 4.50–4.71 (m, 1H), 4.93–5.19 (dd, 2H,
J = 10.2, 15.6 Hz), 5.67–5.85 (m, 1H); 13C NMR (75 MHz, CDCl3):
ꢁ4.8, ꢁ4.4, 19.6, 21.9, 25.5, 25.9, 30.7, 31.1, 37.9, 62.3, 67.4, 73.7,
98.7, 113.5, 141.7; IR (neat): 3450, 2935, 2858, 1465, 1253, 1077,
1029, 996, 836, 776 cmꢁ1; ESI-MS: m/z 329 [M+H]+.
4.1.11. (2R,5R)-5-{[1-(tert-Butyl)-1,1-dimethylsilyl]oxy}-6-
hepten-2-ol 7
To the THP ether 23 (0.42 g, 1.30 mmol) in methanol (20 mL),
commercial NH4Cl (0.34 g, 6.5 mmol) was added and heated at
reflux for 2–3 h. Methanol was removed, diluted with water
(10 mL) and extracted with ether (3 ꢂ 20 mL). The combined ether
extracts were dried over Na2SO4. Evaporation of solvent, followed
by column chromatography (silica gel, 60–120 mesh, EtOAc/hex-
ane, 1:9) to afford THP cleaved product 7 (0.2 g, 65% yield) as a col-
(1.69 g, 75%) as a viscous liquid. ½a D25
ꢃ
¼ þ15:1 (c 1.15, CHCl3); 1H
NMR (300 MHz, CDCl3): 1.06–1.28 (dd 3H, J = 5.3, 6.2 Hz), 1.39–
1.92 (m, 10H), 2.81–3.02 (m, 2H), 3.29–3.52 (m, 1H), 3.53–3.66
(m, 1H), 3.66–3.95 (m, 3H), 4.51–4.68 (m, 1H); 13C NMR
(75 MHz, CDCl3): 19.6, 21.5, 25.4, 30.6, 31.3, 33.5, 55.8, 58.5,
62.3, 67.2, 73.5, 98.8; IR (neat): 3442, 2940, 2867, 1453, 1129,
orless liquid. ½a D25
ꢃ
¼ ꢁ0:8 (c 0.7, CHCl3); 1H NMR (200 MHz, CDCl3):
0.04 (d, 6H, J = 3.6 Hz), 0.91 (m, 9H), 1.22–1.70 (m, 7H), 3.54–3.72
(m, 1H), 4.00–4.18 (m, 1H), 4.94–5.23 (dd, 2H, J = 10.2, 17.6 Hz),
5.65–5.90 (m, 1H); 13C NMR (75 MHz, CDCl3): ꢁ4.8, ꢁ4.4, 21.2,
25.8, 32.7, 37.7, 62.9, 73.7, 113.6, 141.6; IR (neat): 3416, 2930,
2857, 1253, 1083, 836, 773, 677 cmꢁ1; HRMS: m/z [M+Na]+ calcd
for C13H28O2SiNa: 267.1756; found: 267.1769.
1074, 1026, 995, 871 cmꢁ1
;
HRMS: m/z [M+Na]+ calcd for
C12H22O4Na: 253.1415; found: 253.1423.
4.1.8. (1R)-3-[(2R,3S)-3-(Iodomethyl)oxiran-2-yl]-1-
methylpropyl tetrahydro-2H-2-pyranyl ether 21
To a stirred solution of 20 (0.45 g, 1.96 mmol) in ether/acetoni-
trile (3:1) (20 mL), TPP (0.77 g, 2.94 mmol) and imidazole (0.26 g,
3.92 mmol) were added at 0 °C and stirred for 5 min. I2 (0.74 g,
2.94 mmol) was added at 0 °C and stirred for 1 h. The reaction mix-
ture was quenched with saturated sodium thiosulfate (15 mL) and
extracted with EtOAc (3 ꢂ 30 mL). The organic layer was washed
with water (10 mL), brine (10 mL), and dried (Na2SO4). The solvent
4.1.12. tert-Butyl[((1R,4R,8S)-8-{[1-(tert-butyl)-1,1-dimethylsilyl]
oxy}-4-methyl-6-methylene-1-vinyl-9-decenyl)oxy]dimethyl-
silane 24
To a stirred solution of acid 6 (207 mg, 0.901 mmol) in dry
CH2Cl2 (20 mL) at 0 °C DCC and cat. DMAP were added. After
10 min alcohol 7 (222 mg, 0.902 mmol) in dry CH2Cl2 (10 mL)
was added and stirred at rt for 6 h. The reaction mixture was

G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 1330–1336
1335
evaporated and the residue was purified by column chromatog-
4.1.17. (E)-6-(Tetrahydro-2H-2-pyranyloxy)-2-hexen-1-ol 27
raphy (silica gel, 60–120 mesh, EtOAc/hexane, 1:24) to afford 24
The compound 27 was prepared from 26 (5.9 g, 24.38 mmol) as
a yellow liquid in 80% yield following the procedure described for
compound 19. 1H NMR (200 MHz, CDCl3): 1.36–1.94 (m, 8H), 2.04–
2.24 (m, 2H), 3.27–3.56 (m, 2H), 3.63–3.92 (m, 2H), 4.00–4.13 (m,
2H), 4.54 (t, 1H, J = 2.9 Hz), 5.61–5.73 (m, 2H); 13C NMR (75 MHz,
CDCl3): 19.6, 25.4, 26.0, 28.4, 30.6, 62.4, 63.5, 66.8, 98.9, 129.2,
(350 mg, 85% yield) as a colorless liquid. ½a D25
¼ ꢁ7:7 (c 0.4,
ꢃ
CHCl3); 1H NMR (300 MHz, CDCl3): 0.02 (s, 12H), 0.87 (d, 18H,
J = 6.8 Hz), 1.16–1.22 (d, 3H, J = 6.0 Hz), 1.34–1.67 (m, 4H), 2.35
(dd, 1H, J = 5.3, 14.3 Hz), 2.47 (dd, 1H, J = 7.5, 14.3 Hz), 3.98–
4.12 (m, 1H), 4.49–4.59 (m, 1H), 4.78–4.92 (m, 1H), 4.96–5.25
(m, 4H), 5.66–5.89 (m, 2H); 13C NMR (75 MHz, CDCl3): ꢁ4.8,
ꢁ4.4, 20.0, 25.8, 31.4, 37.6, 43.9, 64.5, 70.8, 73.6, 113.9, 114.6,
140.3, 141.3, 170.6; IR (neat): 2955, 2931, 2858, 1737, 1467,
130.2; IR (neat): 3383, 2933, 2863, 1443, 1378, 1024, 971 cmꢁ1
;
HRMS: m/z [M+Na]+ calcd for C11H20O3Na: 223.2272; found:
223.2278.
1254, 1085, 1030, 924, 835, 776, 679 cmꢁ1
; HRMS: m/z
[M+Na]+ calcd for C24H48O4Si2Na: 479.2988; found: 479.2984.
4.1.18. {(2R,3R)-3-[3-(Tetrahydro-2H-2-
pyranyloxy)propyl]oxiran-2-yl}methanol 28
The compound 28 was prepared from 27 (3.7 g, 18.5 mmol) as a
yellow liquid in 80% yield following the procedure described for
compound 20.
4.1.13. (3S,7R,10R)-3,10-Dihydroxy-7-methyl-1,11-
dodecadiene-5-one 5
To a stirred solution of compound 24 (342 mg, 0.75 mmol) in dry
THF (30 mL) at 0 °C TBAF was added and stirred at rt for 2 h. The reac-
tion mixturewas evaporatedandtheresidue waspurified bycolumn
chromatography (silica gel, 60–120 mesh, EtOAc/hexane, 3:7) to af-
½
a 2D5
ꢃ
¼ þ17:5 (c 2.95, CHCl3); 1H NMR (300 MHz, CDCl3): 1.42–
1.94 (m, 10H), 2.90 (m, 1H), 2.98 (m, 1H), 3.34–3.55 (m, 2H),
3.57–3.69 (m, 1H), 3.70–3.92 (m, 3H), 4.57 (s, 1H); 13C NMR
(75 MHz, CDCl3): 19.6, 25.3, 26.0, 28.5, 30.6, 55.7, 58.4, 61.7,
62.4, 68.8, 98.9; IR (neat): 3425, 2936, 2867, 1448, 1123, 1028,
986 cmꢁ1; HRMS: m/z [M+Na]+ calcd for C11H20O4Na: 239.1753;
found: 239.1745.
ford 5 (120 mg, 70% yield) as a colorless liquid. ½a D25
¼ ꢁ6:6 (c 0.75,
ꢃ
CHCl3); 1H NMR (300 MHz, CDCl3): 1.22–1.28 (d, 3H, J = 6.8 Hz),
1.42–1.81 (m, 4H), 2.39–2.49 (m, 2H), 3.07 (s, 1H, OH), 4.03–4.18
(m, 1H), 4.50 (m, 1H), 4.91–5.04 (m, 1H), 5.06–5.35 (m, 4H), 5.76–
5.93 (m, 2H); 13C NMR (75 MHz, CDCl3): 20.0, 31.6, 36.3, 41.4, 64.6,
68.9, 72.9, 115.0, 115.3, 138.8, 140.9, 172.3; IR (neat): 3410, 2928,
2867, 1719, 1424, 1276, 1174, 925, 771 cmꢁ1; HRMS: m/z [M+Na]+
calcd for C12H20O4Na: 251.1259; found: 251.1270.
4.1.19. 2-{3-[(2R,3S)-3-(Iodomethyl)oxiran-2-
yl]propoxy}tetrahydro-2H-2-pyran 29
The compound 29 was prepared from 28 (3.5 g, 16.20 mmol) as
a yellow liquid in 93% yield following the procedure described for
compound 21. ½a 2D5
ꢃ
¼ ꢁ3:8 (c 2.4, CHCl3); 1H NMR (300 MHz,
4.1.14. (4S,7R,10R)-4,7-Dihydroxy-10-methyl-3,4,7,8,9,10-
hexahydro-2H-2-oxecinone 3
CDCl3): 1.41–1.91 (m, 10H), 2.81 (m, 1H), 2.91–3.04 (m, 2H),
3.20–3.33 (m, 1H), 3.35–3.54 (m, 2H), 3.68–3.88 (m, 2H), 4.56
(m, 1H); 13C NMR (75 MHz, CDCl3): 4.8, 19.5, 25.3, 26.0, 28.6,
30.6, 56.5, 58.2, 62.2, 66.7, 98.8; IR (neat): 3449, 2940, 2867,
Grubbs’s catalyst II (44 mg, 0.052 mmol, 10 mol %) was dis-
solved in CH2Cl2 (10 mL) and was added dropwise to a refluxing
solution of the compound 5 (120 mg, 0.526 mmol) in CH2Cl2
(200 mL). Refluxing was continued for 3 h by which time all the
starting material was consumed (TLC). The solvent was removed
in vacuo, and the crude residue was purified by column chroma-
tography (silica gel, 60–120 mesh, EtOAc/hexane, 7:2) to afford 3
1447, 1125, 1031, 900 cmꢁ1
;
HRMS: m/z [M+Na]+ calcd for
C11H19O3INa: 349.2354; found: 349.2341.
4.1.20. (3R)-6-(Tetrahydro-2H-2-pyranyloxy)-1-hexen-3-ol 30
The compound 30 was prepared from 29 (4 g, 12.2 mmol) as a
yellow liquid in 80% yield following the procedure described for
(73 mg, 70% yield).
½
a 2D5
ꢃ
¼ ꢁ29:2 (c 0.5, MeOH); 1H NMR
(400 MHz, CDCl3): 1.22 (d, 3H, J = 6.8 Hz), 1.32–1.47 (m, 2H),
1.68–1.75 (m, 1H), 1.90–2.01 (m, 1H), 2.05–2.10 (dd, 1H, J = 5.9,
14.3 Hz), 2.82–2.89 (dd, 1H, J = 7.3, 14.3 Hz), 4.62–4.69 (m, 1H),
4.82–4.91 (m, 1H), 4.93–5.04 (m, 1H), 5.19–5.27 (m, 1H), 5.31–
5.41 (dd, 1H, J = 9.0, 11.4 Hz); 13C NMR (75 MHz, CDCl3): 20.3,
31.4, 36.8, 43.6, 66.0, 67.4, 71.4, 133.0, 134.6, 170.5; IR (neat):
3421, 2930, 1717, 1638, 1282 cmꢁ1; HRMS: m/z [M+Na]+ calcd
for C10H16O4Na: 223.1043; found: 223.1045.
compound 22. ½a 2D5
ꢃ
¼ ꢁ9:1 (c 0.45, CHCl3); 1H NMR (300 MHz,
CDCl3): 1.34–1.92 (m, 10H), 2.26 (s, 1H, OH), 3.31–3.53 (m, 2H),
3.68–3.88 (m, 2H), 4.12 (m, 1H), 4.58 (m, 1H), 5.07 (d, 1H,
J = 10.5 Hz), 5.22 (d, 1H, J = 17.3 Hz), 5.74–5.92 (m, 1H); 13C NMR
(75 MHz, CDCl3): 19.5, 25.3, 26.0, 30.6, 34.2, 62.0, 67.4, 73.4,
98.8, 113.8, 141.5; IR (neat): 3447, 2925, 2855, 1638, 1121, 1028,
;
990, 759 cmꢁ1 HRMS: m/z [M+Na]+ calcd for C11H20O3Na:
223.1936; found: 223.1932.
4.1.15. 4-(Tetrahydro-2H-2-pyranyloxy)-1-butanol 25
The compound 25 was prepared from 12 (5 g, 55.55 mmol) as a
yellow liquid in 82% yield following the procedure described for
compound 16 . 1H NMR (200 MHz, CDCl3): 1.43–1.94 (m, 10H),
2.18 (s, 1H, OH), 3.32–3.56 (m, 2H), 3.64 (m, 2H), 3.71–3.91 (m,
2H), 4.58 (m, 1H); IR (neat): 3418, 2942, 2870, 1201, 1120, 1068,
1027 cmꢁ1; HRMS: m/z [M+Na]+ calcd for C9H18O3Na: 197.1516;
found: 197.1513.
4.1.21. tert-Butyl(dimethyl)({(1R)-1-[3-(tetrahydro-2H-2-
pyranyloxy)propyl]-2-propenyl}oxy)silane 31
The compound 31 was prepared from 30 (1 g, 3.34 mmol) as a
yellow liquid in 95% yield following the procedure described for
compound 23. ½a 2D5
ꢃ
¼ ꢁ7:1 (c 1.95, CHCl3); 1H NMR (300 MHz,
CDCl3): 0.02 (s, 3H), 0.04 (s, 3H), 0.89 (s, 9H), 1.34–1.92 (m, 10H),
3.27–3.54 (m, 2H), 3.60–3.90 (m, 2H), 4.07–4.19 (m, 1H), 4.55 (s,
1H), 5.01 (d, 1H, J = 9.8 Hz), 5.13 (d, 1H, J = 17.3 Hz), 5.68–5.88
(m, 1H); 13C NMR (75 MHz, CDCl3): ꢁ4.8, ꢁ4.4, 19.5, 25.3, 25.4,
25.8, 30.7, 34.6, 62.2, 67.5, 73.5, 98.6, 113.6, 141.5; IR (neat):
4.1.16. Ethyl (E)-6-(tetrahydro-2H-2-pyranyloxy)-2-hexenoate 26
The compound 26 was prepared from 25 (4.7 g, 27.52 mmol) as
a yellow liquid in 90% yield following the procedure described for
compound 18. 1H NMR (200 MHz, CDCl3): 1.23–1.90 (m, 11H),
2.24–2.55 (m, 2H), 3.29–3.55 (m, 2H), 3.65–3.88 (m, 2H), 4.21
(m, 2H), 4.55 (m, 1H), 5.80 (d, 1H, J = 15.5 Hz), 6.86–7.15 (m,
1H); IR (neat): 2941, 2870, 1723, 1367, 1262, 1202, 1125, 1036,
982 cmꢁ1; HRMS: m/z [M+Na]+ calcd for C13H22O4Na: 265.2381;
found: 265.2375.
2933, 2858, 1467, 1253, 1032, 836, 775 cmꢁ1
; HRMS: m/z
[M+Na]+ calcd for C17H34O3SiNa: 337.2879; found: 337.2883.
4.1.22. (4R)-4-{[1-(tert-Butyl)-1,1-dimethylsilyl]oxy}-5-hexen-
1-ol 11
The compound 11 was prepared from 31 (1 g, 3.34 mmol) as a
yellow liquid in 65% yield following the procedure described for
compound 7. ½a 2D5
ꢃ
¼ ꢁ5:3 (c 2.55, CHCl3); 1H NMR (300 MHz,

1336
G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 1330–1336
CDCl3): 0.01 (s, 3H), 0.02 (s, 3H), 0.87 (s, 9H), 1.46–1.64 (m, 4H),
1.78 (br s, 1H, OH), 3.50–3.64 (m, 2H), 4.09–4.19 (m, 1H), 4.97–
5.04 (d, 1H, J = 10.5 Hz), 5.06–5.16 (d, 1H, J = 16.6 Hz), 5.67–5.82
(m, 1H); 13C NMR (75 MHz, CDCl3): ꢁ4.9, ꢁ4.5, 25.8, 28.0, 34.4,
62.8, 73.4, 113.9, 141.0; IR (neat): 3365, 2930, 2857, 1467, 1253,
3425, 2929, 1724, 1264 cmꢁ1; HRMS: m/z [M]+ calcd for C9H14O4:
186.1041; found: 186.1048.
Acknowledgment
1058, 1029, 835, 776 cmꢁ1
;
HRMS: m/z [M+Na]+ calcd for
P.P. and K.S. thank UGC, New Delhi, for the award of a
fellowship.
C12H26O2SiNa: 231.1307; found: 231.1298.
References
4.1.23. tert-Butyl[((1R,8S)-8-{[1-(tert-butyl)-1,1-dimethylsilyl]
oxy}-6-methylene-1-vinyl-9-decenyl)oxy]dimethylsilane 32
The compound 32 was prepared from 6 (200 mg, 0.87 mmol) as
a yellow liquid in 80% yield following the procedure described for
1. Kittakoop, P.; Punya, J.; Kongsaeree, P.; Lertwerawat, Y.; Jintasirikul, A.;
Tanticharoen, M.; Thebtaranonth, Y. Phytochemistry 1999, 52, 453–457.
2. Isaka, M.; Tanticharoen, M.; Kongsaree, P.; Thebtaranonth, Y. J. Org. Chem. 2001,
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compound 24. ½a 2D5
ꢃ
¼ ꢁ2:8 (c 0.7, CHCl3); 1H NMR (200 MHz,
CDCl3): 0.04 (s, 12H), 0.88 (d, 18H, J = 5.4 Hz), 1.44–1.76 (m, 4H),
2.31–2.44 (dd, 1H, J = 5.4, 14.8 Hz), 2.44–2.58 (dd, 1H, J = 7.8,
14.8 Hz), 3.97–4.18 (m, 3H), 4.48–4.62 (m, 1H), 4.97–5.28 (m,
4H), 5.63–5.94 (m, 2H); 13C NMR (75 MHz, CDCl3): ꢁ4.8, ꢁ4.4,
25.7, 25.8, 34.2, 43.7, 64.6, 70.8, 73.2, 114.0, 114.6, 140.2, 141.25,
171.1; IR (neat): 3425, 2924, 2853, 1742, 1462, 1381, 1265,
4. Rukachaisirikul, V.; Pramjit, S.; Pakawatchai, C.; Isaka, M.; Supothina, S. J. Nat.
Prod. 2004, 67, 1953–1955.
5. (a) Mohapatra, D. K.; Ramesh, D. K.; Giardello, M. A.; Chorghade, M. S.; Gurjara,
M. K.; Grubbs, R. H. Tetrahedron Lett. 2007, 48, 2621–2625; (b) Liu, J.; Zhang, L.;
He, J.; He, L.; Ma, B.; Pan, X.; She, X. Tetrahedron: Asymmetry 2008, 19, 906–911.
6. (a) Sabitha, G.; Sudhakar, K.; Reddy, N. M.; Rajkumar, M.; Yadav, J. S.
Tetrahedron Lett. 2005, 46, 6567–6570; (b) Sabitha, G.; Narjis, F.; Swapna, R.;
Yadav, J. S. Synthesis 2006, 17, 2879–2884; (c) Sabitha, G.; Reddy, E. V.; Yadagiri,
K.; Yadav, J. S. Synthesis 2006, 19, 3270–3274; (d) Sabitha, G.; Sudhakar, K.;
Yadav, J. S. Tetrahedron Lett. 2006, 47, 8599–8602; (e) Sabitha, G.; Bhaskar, V.;
Yadav, J. S. Tetrahedron Lett. 2006, 47, 8179–8181; (f) Sabitha, G.; Swapna, R.;
Reddy, E. V.; Yadav, J. S. Synthesis 2006, 24, 4242–4246; (g) Sabitha, G.;
Bhikshapathi, M.; Yadav, J. S. Synth. Commun. 2007, 37, 561–569; (h) Sabitha,
G.; Gopal, P.; Yadav, J. S. Synth. Commun. 2007, 37, 1495–1502; (i) Sabitha, G.;
Yadagiri, K.; Yadav, J. S. Tetrahedron Lett. 2007, 48, 1651–1652; (j) Sabitha, G.;
Yadagiri, K.; Yadav, J. S. Tetrahedron Lett. 2007, 48, 8065–8068; (k) Sabitha, G.;
Padmaja, P.; Reddy, K. B.; Yadav, J. S. Tetrahedron Lett. 2008, 49, 919–922; (l)
Sabitha, G.; Padmaja, P.; Yadav, J. S. Helv. Chim. Acta 2008, 91, 2235–2239; (m)
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;
1118 cmꢁ1 HRMS: m/z [M+Na]+ calcd for C23H46O4Si2Na:
465.2133; found: 465.2139.
4.1.24. (4R)-4-Hydroxy-5-hexenyl(3S)-3-hydroxy-4-pentenoate 10
The compound 10 was prepared from 32 (300 mg, 0.67 mmol)
as a yellow liquid in 70% yield following the procedure described
for compound 5. ½a D25
ꢃ
¼ ꢁ3:8 (c 0.55, CHCl3); 1H NMR (300 MHz,
CDCl3): 1.53–1.82 (m, 4H), 2.43–2.60 (m, 2H), 3.33 (s, 1H, OH),
4.05–4.22 (m, 3H), 4.51 (m, 1H), 4.06–5.37 (m, 4H), 5.77–5.94
(m, 2H); 13C NMR (75 MHz, CDCl3): 24.5, 33.0, 41.2, 64.6, 68.9,
72.5, 115.0, 115.4, 138.7, 140.7, 172.2; IR (neat): 3427, 2926,
1723, 1643, 1423, 1278, 1175, 992, 926, 767 cmꢁ1; HRMS: m/z
[M+Na]+ calcd for C11H18O4Na: 237.1102; found: 237.1105.
7. (a) Yadav, J. S.; Deshpande, P. K.; Sharma, G. V. M. Tetrahedron 1990, 46, 7033–
7046; (b) Sabitha, G.; Fatima, N.; Gopal, P.; Reddy, C. N.; Yadav, J. S. Tetrahedron
Asymmetry 2009, 20, 184–191.
8. (a) Dess, B. D.; Martin, J. C. J. Org. Chem. 1983, 48, 4155–4156; (b) Dess, B. D.;
Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277–7287.
9. Dalcanale, E.; Montanari, F. J. Org. Chem. 1986, 51, 567–569.
4.1.25. (4S,7R)-4,7-Dihydroxy-3,4,7,8,9,10-hexahydro-2H-2-
oxecinone 4
10. (a) Schwartz, N. N.; Blumbergs, J. H. J. Org. Chem. 1964, 29, 1976; (b) Schaus, S.
E.; Brandes, B. D.; Larrow, J. F.; Tokunaga, M.; Hansen, K. B.; Gould, A. E.;
Kurrow, M. E.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 1307.
11. (a) Mancuso, A. J.; Brownfain, D. S.; Swern, D. J. Org. Chem. 1979, 44, 4148–
4150; For reviews on the Swern oxidation, see: (b) Tidwell, T. T. Synthesis 1990,
857–870; (c) Tidwell, T. T. Org. React. 1990, 39, 297–572.
12. Garegg, P. J.; Samuelson, B. J. Chem. Soc., Chem. Commun. 1979, 978.
13. Kang, S.-K.; Kim, S.-G.; Cho, D.-G.; Jeon, J.-H. Synth. Commun. 1993, 23, 681.
14. Yadav, J. S.; Srinivas, D.; Reddy, G. S. Synth. Commun. 1998, 28, 1399–1404.
15. Solladie, G.; Gressot-Kempf, L. Tetrahedron: Asymmetry 1996, 116, 1753.
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(b) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953–956.
The compound 4 was prepared from 10 (100 mg, 0.46 mmol) in
70% yield following the procedure described for compound 3. 1H
NMR (300 MHz, CDCl3): 1.25–1.38 (m, 2H), 1.47–1.57 (m, 1H),
1.89–1.98 (m, 1H), 1.98–2.10 (dd, 1H, J = 5.6, 14.8 Hz), 2.25 (s,
1H, OH), 2.75–2.89 (dd, 1H, J = 7.5, 14.8 Hz), 4.20–4.29 (t, 2H,
J = 7.0 Hz), 4.35–4.44 (m, 1H), 4.68–4.78 (m, 1H), 5.15–5.25 (m,
1H), 5.46–5.59 (dd, 1H, J = 9.7, 11.5 Hz); 13C NMR (75 MHz, CDCl3):
25.0, 33.4, 41.6, 65.4, 69.0, 71.6, 131.4, 133.6, 170.8; IR (neat):