Total synthesis of nonenolide

Article abstract of DOI:10.1002/hlca.200900410

A novel synthetic route has been reported for the synthesis of nonenolide. The syntheses of fragments were initiated from commercially available and inexpensive starting materials. The synthesis involves key steps like Sharpless epoxidation, Jacobsen's re

Full text of DOI:10.1002/hlca.200900410

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Helvetica Chimica Acta – Vol. 93 (2010)
Total Synthesis of Nonenolide
by Harshadas Mitaram Meshram*, Dachepally Aravind Kumar, and Palakuri Ramesh
Discovery Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology,
Hyderabad – 500007, India
(fax: þ 91(40)27160512; e-mail: hmmeshram@yahoo.com)
A novel synthetic route has been reported for the synthesis of nonenolide. The syntheses of
fragments were initiated from commercially available and inexpensive starting materials. The synthesis
involves key steps like Sharpless epoxidation, Jacobsenꢀs resolution, lactonization, and cross-metathesis.
Introduction. – Nature gave us many biologically active metabolites. For example,
the genus Cordyceps, an abundant source of biologically active secondary metabolites,
e.g., antimalarial erythrostominones [1], antimalarial cordypyridones [2], and anti-
tumor sterols [3]. It has been widely used as food and herbal medicine in Asia over the
past years. The rich source of the secondary active metabolites ranging from simple to
structural complex molecules such nonenolide 1 and cephalosporolides 2 [4] continues
to stimulate organic chemists. The ten-membered lactone 1 was isolated from the
entomopathogenic fungus cordyceps militaris BCC 2816 in 2004. It is a white solid and
exhibits good antimalarial activity. The structure was deduced from spectroscopic data
and X-ray crystallographic analysis [5].
There are two reported syntheses [6] starting from mannitol and propylene oxide,
respectively. In both syntheses, ring-closing metathesis (RCM) is the key step, and
Grubbꢀs catalyst has been used to accomplish the reaction. It has been shown
previously that the nonenolide 1 could be derived by RCM reaction of compound 3
[6a], which can be obtained by the coupling of subunits 4 and 5 [6a]. Here, we show that
these subunits can be traced back to l-malic acid (Scheme 1).
Results and Discussion. – The importance and new aspect of the present synthesis
lie in the fact that the same starting material is used for both fragments. The synthesis of
compound 4 is depicted in Scheme 2. Thus, the synthesis of fragment 4 commenced
from l-malic acid. It was converted into 6 in six steps (42%) according to a literature
procedure [7]. The epoxide 6, on exposure to trimethylsulfonium iodide [8] in THF,
ꢁ 2010 Verlag Helvetica Chimica Acta AG, Zꢂrich

Helvetica Chimica Acta – Vol. 93 (2010)
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Scheme 1
afforded a secondary allylic alcohol 7 in good yield (87%). Protection of 7 with para-
methoxybenzyl bromide (PMB-Br) in the presence of NaH gave a mixture of
compounds 8 and 9 (60 :40). As the tert-butyl(diphenyl)silyl ((t-Bu)Ph2Si, TBDPS)
group on the primary OH group has to be removed, we treated the crude compound
with Bu4NF (TBAF) to give the required primary alcohol, which was converted into
acid 4 in two steps with 90% yield (Scheme 2).
Scheme 2
a) (Me)3SþIꢀ, BuLi, THF, ꢀ 108, 1 h; 90%. b) NaH, 4-methoxybenzyl bromide (PMB-Br), Bu4NI
(TBAI), THF, 08 – room temperature. c) Bu4NF (TBAF), THF, room temperature. d) 1. (COCl)2,
DMSO, CH2Cl2, ꢀ 788; 2. NaH2PO4, NaClO2, MeCN, H2O, 2-methylbut-2-ene, room temperature; 90%.
Oxidation of alcohol 10 [9] with PCC gave the corresponding aldehyde, which,
without further purification, was treated with the C1 Wittig reagent [10] to provide allyl
derivative 11 (47%). The latter was subjected to hydroboration with BH3 · SMe2 in
THF, followed by oxidation with H2O2 [11], to give primary alcohol 12 in 84% yield in
two steps. Oxidation of 12 with 2-iodoxybenzoic acid (IBX) furnished the intermediate
aldehyde, and subsequent addition of (trimethylsilyl)acetylene [12] gave a 1:1 mixture
of diasteroisomers 13 (Scheme 3).
Removal of the TMS group in 13 with K2CO3 in MeOH, followed by oxidation of
the secondary alcohol with Dess – Martin periodinane (DMP) [13], provided the
desired ketone 14 in 90% yield. Coreyꢀs chiral oxazaborolidine protocol [14] was
applied to reduce 14 to give 15 in 95% yield (de 86%). The propargylic alcohol was
reduced by using Lindlarꢀs catalyst to furnish the allylic alcohol 16 in 92% yield [15].

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Helvetica Chimica Acta – Vol. 93 (2010)
Scheme 3
a) 1. Pyridinium chlorochromate (PCC), CH2Cl2, room temperature; 2. Ph3PMeþIꢀ, t-BuOK, THF, 08. b)
1. BH3 · Me2S, THF; 2. H2O2, NaOH. c) 1. 2-Iodoxybenzoic acid (IBX), CH2Cl2, DMSO, 08, room
temperature; 2. (trimethylsilyl)acetylene, BuLi, THF, ꢀ 788. d) 1. K2CO3, MeOH; 2. Dess – Martin
periodinane (DMP) oxidation, CH2Cl2, 08; 90%. e) (R)-2-methyl-CBS-oxazaborlidine (CBS ¼ Corey –
Bakshi – Shibata), BH3 · DMS, THF, ꢀ 788. f) PdꢀCaCO3, H2, AcOEt, room temperature. g) NaH,
PMB-Br, TBAI, THF, 08 – room temperature. h) TsOH, MeOH. i) TsCl, Et3N, Bu2SnO, CH2Cl2, room
temperature. j) LiAlH4, THF, 08 – room temperature.
The secondary OH group was protected as its para-methoxybenzyl (PMB) ether to give
17 in 80% yield. The isopropylidene moiety of 17 was hydrolyzed under acidic
conditions with TsOH, in MeOH at room temperature, to furnish 18 in 92% yield. The
fragment 5 was obtained from diol 18 by selective monotosylation [16], followed by
lithium aluminium hydride (LAH) reduction [17] (Scheme 3).
The acid 4 was coupled with alcohol 5 according to Yamaguchi conditions [18] to
give diene ester 3 in 91% yield. Further, we have successfully performed the RCM
reaction on PMB-protected hydroxy compound according to the protocol of Grubbs
and co-workers [6a] and obtained lactone 20 as the major product in 75% yield along
with minor (Z)-isomer. Finally, deprotection of the PMB ether groups gave 1
(Scheme 4).
The authors D. A. K. and P. R. thank CSIR, New Delhi, for the award of fellowships.
Experimental Part
General. Chemicals were purchased from Fluka and S. D. Fine Chemicals. TLC: precoated silica-gel
1
plates (60 F254, 0.2-mm layer; E. Merk). H-NMR Spectra: Varian 200 or Bruker 300 spectrometer; in
CDCl3; d in ppm, J in Hz. Mass spectra: VG Autospec; in m/z.

Helvetica Chimica Acta – Vol. 93 (2010)
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Scheme 4
(3S)-5-{[(tert-Butyl)(diphenyl)silyl]oxy}pent-1-en-3-ol (7). To a suspension of (Me)3SþIꢀ (2.44 g,
12 mmol, 3 equiv.) in dry THF (36 ml) was added BuLi (1.6m in hexane; 7.43 ml; 11.9 mmol, 2.9 equiv.).
After 30 min, (tert-butyl){2-[(2S)-oxiran-2-yl]ethoxy}diphenylsilane (6; 1.14 g, 4.0 mmol) in THF (8 ml)
was introduced producing a milky suspension. The mixture was allowed to warm to 08 over ca. 30 min and
then to r.t., and was stirred for 2 h. The reaction was quenched with H2O at 08, the mixture was extracted
with Et2O, and the combined org. layers were dried (Na2SO4). Chromatography of the crude material
(SiO2; AcOEt/hexane 1:9) afforded 7 (1.02 g, 85%). Colorless oil. [a]2D5 ¼ ꢀ11.2 (c ¼ 1.25, CHCl3). IR
(KBr): 3455, 2931, 2858, 1612, 1512, 1247, 1103, 1036, 821, 705. 1H-NMR: 1.06 (s, 9 H); 1.77 (m, 2 H); 2.92
(br. s, 1 H); 3.90 (m, 2 H); 4.40 (m, 1 H); 5.11 (d, J ¼ 10.2, 1 H); 5.31 (d, J ¼ 16.5, 1 H); 5.81 – 5.90 (m,
1 H); 7.36 – 7.43 (m, 6 H); 7.65 – 7.69 (m, 4 H). 13C-NMR: 19.0; 26.7; 38.2; 55.2; 69.8; 114.2; 129.7; 130.0;
134.4; 138.7. ESI-MS: 363 (90, [M þ Na]þ). HR-ESI-MS: 363.1743 ([M þ Na]þ, C21H28NaO2Siþ; calc.
363.1756).
(tert-Butyl)({(3S)-3-[(4-methoxybenzyl)oxy]pent-4-en-1-yl}oxy)diphenylsilane (8). To a soln. of 7
(2.5 g, 13.4 mmol) in dry THF (40 ml) was added NaH (0.8 g, 33.5 mmol; 60% dispersion in mineral oil)
at 08, the mixture was stirred for 30 min, PMB-Br (2.5 g, 16.0 mmol) was added, and the mixture was
stirred for additional 3 h at r.t. The reaction was quenched by addition of cold H2O, and the aq. layer was
washed with AcOEt (2 ꢁ 25 ml) and dried (Na2SO4). Evaporation of the solvent in vacuo and
purification of the residue by column chromatography (CC; 10% AcOEt/light petroleum ether) to
afforded 8. [a]2D5 ¼ ꢀ5.7 (c ¼ 1.5, CHCl3). IR (KBr): 3029, 2985, 2851, 1555, 1229, 1056, 747. H-NMR:
1
1.01 (s, 9 H); 1.64 – 1.88 (m, 2 H); 3.63 – 3.70 (m, 1 H); 3.73 – 3.80 (m, 1 H); 3.77 (s, 3 H); 3.99 (q, J ¼ 11.3,
1 H); 4.22 (d, J ¼ 11.3, 1 H); 4.47 (d, J ¼ 11.3, 1 H); 5.15 – 5.22 (m, 2 H); 5.76 – 5.76 (m, 1 H); 6.76 (d, J ¼
8.3, 2 H); 7.15 (d, J ¼ 8.3, 2 H); 7.28 – 7.40 (m, 6 H); 7.58 – 7.61 (m, 4 H). 13C-NMR: 19.3; 27.0; 38.6; 55.0;
60.1; 69.8; 76.9; 113.6; 116.8; 127.6; 129.1; 129.5; 130.8; 133.9; 135.5; 139.2; 159.0. ESI-MS: 483 (88, [M þ
Na]þ). HR-ESI-MS: 483.2347 ([M þ Na]þ, C29H36NaO3Siþ; calc. 483.2331).
(3S)-3-[(4-Methoxybenzyl)oxy]pent-4-en-1-ol (9). To compound 8 (0.9 g, 1.9 mmol) in dry THF
(10 ml) was added TBAF (1.9 ml, 1.9 mmol; 1m soln. in THF) dropwise at 08, and the mixture was stirred
for 30 min. H2O (2 ml) was added, and the mixture was extracted with AcOEt. The org. extracts were
washed with brine and dried (anh. Na2SO4). Evaporation of the solvent afforded 9 (0.35 g, 80%). Liquid.
[a]2D5 ¼ ꢀ34 (c ¼ 1.0, CHCl3). IR (KBr): 3428, 2933, 2862, 1612, 1513, 1301, 1247, 1176, 1092, 820.
1H-NMR: 1.69 – 1.87 (m, 2 H); 3.53 – 3.68 (m, 2 H); 3.79 (s, 3 H); 4.25 – 4.31 (m, 1 H); 4.42 (s, 2 H); 5.06
(td, J ¼ 1.5, 1.8, 1 H); 5.23 (td, J ¼ 1.5, 1.7, 1 H); 6.83 (d, 2 H, J ¼ 8.6); 7.20 (d, 2 H, J ¼ 8.6). 13C-NMR:
37.5; 55.0; 59.9; 72.6; 78.9; 113.6; 117.2; 128.3; 129.2; 138.0; 158.9. ESI-MS: 245 (69, [M þ Na]þ). HR-ESI-
MS: 245.2753 ([M þ Na]þ, C13H18NaO3þ ; calc. 245.1154).
(3S)-3-[(4-Methoxybenzyl)oxy]pent-4-enoic acid (4). To a soln. of oxalyl chloride (18.8 ml,
215.5 mmol) in CH2Cl2 (500 ml) at ꢀ 788 was added DMSO (19.4 ml, 273.0 mmol) over 20 min. The
resulting mixture was stirred for an additional 15 min, and then 9 (31.9 g, 143.7 mmol), dissolved in
CH2Cl2 (100 ml), was added dropwise. The mixture was stirred for 30 min, and Et3N (120.2 ml,
862.1 mmol) was added dropwise. The mixture was allowed to warm to r.t. and stirred for 30 min. After
completion of the reaction, H2O was added (400 ml), and the aq. phase was extracted with CH2Cl2 (2 ꢁ
200 ml). The combined org. layers were washed with brine and dried (anh. Na2SO4), removal of the
solvent afforded the corresponding aldehyde (28.5 g, 90%) as a colorless liquid.
To a stirred soln. of the intermediate aldehyde in t-BuOH (1 ml) was added methyl-2-butene (0.5 ml)
in t-BuOH (0.5 ml). The mixture was cooled (08) and treated with a soln. of NaClO2 (36 mg, 0.3 mmol)

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Helvetica Chimica Acta – Vol. 93 (2010)
and NaH2PO4 (142 mg, 0.91 mmol) in H2O (1 ml). After 1.5 h, the mixture was diluted with brine (3 ml)
and Et2O (3 ml). The org. phase was separated, and the aq. phase was extracted with Et2O. The combined
org. phases were washed with brine, dried (Na2SO4), and concentrated in vacuo. Flash chromatography
(FC; Et2O) afforded 4 (38.2 mg, 58%). Rf (SiO2, 30% AcOEt in hexane) 0.25. [a]2D5 ¼ þ29.14 (c ¼ 1,
CHCl3). IR (KBr): 3412, 2929, 1716, 1624, 1513, 1248, 1039, 827. 1H-NMR: 2.48 (dd, J ¼ 5.27, 15.41, 1 H);
2.64 (dd, J ¼ 8.08, 15.41, 1 H); 3.80 (s, 3 H); 4.24 (m, 1 H); 4.32 (d, J ¼ 11.24, 1 H); 4.52 (d, J ¼ 11.24, 1 H);
5.26 – 5.38 (m, 2 H); 5.76 (m, 1 H); 6.83 – 6.87 (m, 2 H); 7.21 – 7.26 (m, 2 H). 13C-NMR: 41.0; 55.17; 70.22;
76.20; 113.76; 118.30; 130.0; 137.0; 159.20; 176.17. ESI-MS: 259 (85, [M þ Na]þ). HR-ESI-MS: 259.0935
[M þ Na]þ, C13H16NaOþ4 ; calc. 259.0946).
(3R)-5-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]pent-1-yn-3-ol (15). (R)-2-methyl-CBS-oxazaboroli-
dine (10 ml, 1.0m in toluene) was added to a soln. of ketone 14 (1.82 g, 10 mmol) in 10 ml of toluene,
and the mixture was cooled it to ꢀ 788. BH3 · DMS (20 ml, 1.0m in THF) was added dropwise, and stirring
was continued for 12 h at ꢀ 788. The reaction was quenched with 15 ml of MeOH, and the mixture was
allowed to warm to r.t. The mixture was diluted with Et2O (50 ml) and washed with 1n NaOH, saturated
with NaHCO3, until the aq. washings were colorless. The org. layer was washed with brine, dried (anh.
Na2SO4), and concentrated in vacuo. Purification by FC gave 15 (1.58 g, 8.6 mmol, 86%). Yellow liquid.
[a]2D5 ¼ þ24.0 (c ¼ 1, CHCl3). IR (KBr): 3436, 3097, 2979, 2871, 2230,1643, 1457, 1369, 1226, 1055, 922.
1H-NMR: 1.31 (s, 3 H); 1.37 (s, 3 H); 1.62 – 1.98 (m, 4 H); 2.37 (d, J ¼ 2.19, 1 H); 3.49 (t, J ¼ 8.05, 1 H);
3.88 – 3.98 (m, 2 H); 4.30 – 4.44 (m, 1 H). 13C-NMR: 25.1; 26.6; 34.1; 61.9; 67.6; 72.6; 79.9; 84.7; 108.9.
ESI-MS: 207 (80, [M þ Na]þ). HR-ESI-MS: 207.0980 ([M þ Na]þ, C10H16NaOþ3 ; calc. 207.0997).
(3R)-5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]pent-1-en-3-ol (16). Lindlarꢀs catalyst (0.03 g) and
quinoline (0.12 g) were added to a soln. of 15 (1.84 g, 10 mmol) in AcOEt (12 ml), and the mixture
was stirred under H2 for 2 h. The heterogeneous soln. was filtered through Celite. The org. layer was
concentrated in vacuo. Purification by CC (SiO2) gave 16 (1.71 g, 9.2 mmol, 92%). Yellow syrup. [a]D25
¼
þ12.0 (c ¼ 1, CHCl3). IR (KBr): 3436, 3079, 2986, 2871, 1644, 1455, 1379, 1216, 1058, 922, 757. 1H-NMR:
1.35 (s, 3 H); 1.41 (s, 3 H); 1.58 – 1.75 (m, 4 H); 2.15 (br. s, 1 H); 3.51 (t, J ¼ 6.8, 1 H); 4.01 – 4.16 (m, 3 H);
5.08 – 5.29 (m, 2 H); 5.78 – 5.95 (m, 1 H). 13C-NMR: 25.7; 26.8; 29.2; 33.1; 69.4; 72.4; 76.0; 108.8; 114.6;
140.9. ESI-MS: 209 (87, [M þ Na]þ). HR-ESI-MS: 209.1147 ([M þ Na]þ, C10H18NaOþ3 ; calc. 209.1153).
(4S)-4-{(3R)-3-[(4-Methoxybenzyl)oxy]pent-4-en-1-yl}-2,2-dimethyl-1,3-dioxolane (17). To a soln.
of 16 (1.87 g, 10.05 mmol) in dry DMF (30 ml) was added NaH (0.6 g, 25.1 mmol; 60% dispersion in
mineral oil) at 08, and the mixture was stirred for 30 min. Then, PMB-Br (1.87 g, 12.0 mmol) was added,
and the soln. was stirred for additional 3 h at r.t. The reaction was quenched by cold H2O, and the aq.
layer was extracted with AcOEt (2 ꢁ 25 ml) and dried (anh. Na2SO4). Evaporation of the solvent in
vacuo gave a residue which was purified by CC (10% AcOEt/light petroleum ether) to afford 17 (2.73 g,
8.9 mmol, 89%). Yellow syrup. [a]2D5 ¼ þ14.0 (c ¼ 1, CHCl3). IR (KBr): 3067, 2986, 2868, 1645, 1460,
1
1362, 1051, 752. H-NMR: 1.34 (s, 3 H); 1.39 (s, 3 H); 1.46 – 1.78 (m, 4 H); 3.36 – 3.80 (m, 3 H); 3.80 (s,
3 H); 3.97 (d, J ¼ 11.4, 1 H); 4.26 (d, J ¼ 11.5, 1 H); 4.55 (m, 1 H); 5.18 – 5.28 (m, 2 H); 5.64 – 5.85 (m,
1 H); 6.84 – 6.89 (m, 2 H); 7.22 – 7.27 (m, 2 H). 13C-NMR: 26.2; 29.0; 55.8; 69.2; 72.8; 76.2; 82.8; 109.2;
114.1; 115.7; 129.6; 139.8; 159.7. ESI-MS: 307 (84, [M þ H]þ). HR-ESI-MS: 307.1904 ([M þ H]þ,
C18H27Oþ4 ; calc. 307.1909).
(2S,5R)-5-[(4-Methoxybenzyl)oxy]hept-6-ene-1,2-diol (18). A soln. of 17 (1.83 g, 6.0 mmol) in 80%
AcOH (25 ml) was stirred for 6 h at r.t., and the reaction was quenched with sat. NaHCO3 soln. The aq.
layer was washed with AcOEt (2 ꢁ 30 ml), dried (anh. Na2SO4), and the solvent was evaporated in vacuo.
The residue was purified by CC (SiO2, 60 – 120 mesh; 50% EtOAc/hexane) to give 18 (1.46 g, 5.52 mmol,
92%). Colorless liquid. [a]2D5 ¼ þ17.3 (c ¼ 1, CHCl3). IR (KBr): 3409, 3076, 3000, 2936, 2868, 1612, 1514,
1442, 1302, 1248, 1174, 1072, 995, 821. 1H-NMR: (CDCl3, 200 MHz): 1.43 – 1.57 (m, 2 H); 1.64 – 1.75 (m,
2 H); 2.41 (br. s, 2 H); 3.38 (m, 1 H); 3.53 – 3.75 (m, 3 H); 3.79 (s, 3 H); 4.24 (d, J ¼ 11.4, 1 H); 4.50 (d, J ¼
11.3, 1 H); 5.16 – 5.29 (m, 2 H); 5.66 – 5.84 (m, 1 H); 6.83 – 6.87 (m, 2 H); 7.19 – 7.26 (m, 2 H). 13C-NMR:
28.9; 31.5; 55.1; 66.5; 69.8; 71.9; 80.2; 113.7; 117.3; 129.4; 130.3; 138.6; 159.1. ESI-MS: 266 (56, Mþ). HR-
ESI-MS: 266.1513 (Mþ, C15H22O4þ ; calc. 266.1519).
(2S,5R)-2-Hydroxy-5-[(4-methoxybenzyl)oxy]hept-6-en-1-yl 4-Methylbenzenesulfonate (19). To a
soln. of 18 (1.0 g, 3.75 mmol) in dry CH2Cl2 (30 ml) were added Et3N (0.44 g, 4.27 mmol), Bu2SnO
(0.47 g, 1.89 mmol), 4-(dimethylamino)pyridine (DMAP; 13.8 mg, 0.12 mmol), and TsCl (0.74 g,

Helvetica Chimica Acta – Vol. 93 (2010)
1427
3.84 mmol) at 08. The mixture was stirred for 12 h at r.t., and the reaction was quenched with a sat. soln.
of NaHCO3. The aq. layer was extracted with AcOEt (2 ꢁ 25 ml), and the combined org. layer was
washed with brine, dried (anh. Na2SO4), and concentrated in vacuo. The residue was purified by CC
(SiO2, 60 – 120 mesh; 15% AcOEt/hexane) to afford 19 (1.2 g, 2.85 mmol, 76%). Colorless liquid. [a]D25
¼
þ23.0 (c ¼ 1, CHCl3). IR (KBr): 3410, 3067, 2998, 2925, 2852, 1606, 1512, 1420, 1239, 1070, 820. 1H-NMR:
1.43 – 1.71 (m, 4 H); 2.45 (s, 3 H); 3.66 – 3.78 (m, 2 H); 3.80 (s, 3 H); 3.85 – 3.98 (m, 2 H); 4.21 (d, J ¼ 11.5,
1 H); 4.49 (d, J ¼ 11.4, 1 H); 5.16 – 5.26 (m, 2 H); 5.71 (m, 1 H); 6.83 – 6.87 (m, 2 H); 7.18 – 7.22 (m, 2 H);
7.31 – 7.35 (m, 2 H); 7.76 – 7.80 (m, 2 H). 13C-NMR: 21.3; 28.0; 28.9; 55.6; 70.9; 72.6; 73.7; 82.8; 114.4;
115.7; 128.4; 129.6; 129.8; 130.5; 139.8; 140.3; 144.4; 159.7. ESI-MS: 421 (80, [M þ H]þ). HR-ESI-MS:
421.1697 ([M þ H]þ, C22H29O6Sþ; calc. 421.1685).
(2R,5R)-5-[(4-Methoxybenzyl)oxy]hept-6-en-2-ol (5). To a soln. of 19 (0.420 g, 1 mmol) in dry THF
(20 ml) at 08 was added LAH (0.152 g, 4.0 mmol), and the mixture was stirred for 3 h. Excess of LAH was
removed by addition of a sat. Na2SO4 soln. (3 ml). The solid formed was filtered through Celite pad,
washed with AcOEt, and the filtrate was concentrated in vacuo and purified by CC (SiO2; 20% AcOEt/
hexane) to afford 5 (0.220 g, 0.88 mmol, 88%). Colorless liquid. [a]2D5 ¼ þ19.6 (c ¼ 1.1, CHCl3). IR
1
(KBr): 3436, 3079, 2986, 2871, 1644, 1455, 1379, 1216, 1058, 922, 757. H-NMR: 1.15 (d, J ¼ 6.0, 3 H);
1.44 – 1.53 (m, 2 H); 1.62 – 1.68 (m, 2 H); 2.14 (br. s, 1 H); 3.70 – 3.73 (m, 2 H); 3.80 (m, 3 H); 4.24 (d, J ¼
11.3, 1 H); 4.47 (d, J ¼ 11.3, 1 H); 5.16 – 5.26 (m, 2 H); 5.78 (m, 1 H); 6.84 – 6.84 (m, 2 H); 7.21 – 7.26 (m,
2 H).13C-NMR: 23.1; 31.9; 34.6; 55.1; 67.4; 69.7; 80.1; 113.5; 116.0; 128.6; 130.4; 135.8; 159.0. ESI-MS: 250
(92, Mþ). HR-ESI-MS: 250.1574 (Mþ, C15H22Oþ3 ; calc. 250.1568).
REFERENCES
[1] P. Kittakoop, J. Punya, P. Kongsaeree, Y. Lertwerawat, A. Jintasirikul, M. Tanticharoen, Y.
Thebtaranonth, Phytochemistry 1999, 52, 453.
[2] M. Isaka, M. Tanticharoen, P. Kongsaree, Y. Thebtaranonth, J. Org. Chem. 2001, 66, 4803.
[3] J. W. Bok, L. Lermer, J. Chilton, H. G. Klingeman, G. H. N. Towers, Phytochemistry 1999, 51, 891.
[4] M. J. Ackland, J. R. Hanson, P. B. Hitchcock, A. H. Ratcliffe, J. Chem. Soc., Perkin Trans. 1 1985, 843.
[5] V. Rukachaisisrikul, S. Pramjit, C. Pakawatchai, M. Isaka, S. Supothina, J. Nat. Prod. 2004, 67, 1953.
[6] a) D. K. Mohapatra, D. K. Ramesh, M. A. Giardello, M. S. Chorghade, M. K. Gurjar, R. H. Grubbs,
Tetrahedron Lett. 2007, 48, 2621; b) J. Liu, L. Zhang, J. He, L. He, B. Ma, X. Pan, X. She, Tetrahedron:
Assymmetry 2008, 19, 906.
[7] G. V. M. Sharma, C. G. Reddy, Tetrahedron Lett. 2004, 45, 7483.
[8] L. Alcaraz, J. J. Harnett, C. Mioskowski, J. P. Martel, T. Le Gall, D.-S. Shin, J. R. Falck, Tetrahedron
Lett. 1994, 35, 5449.
´
[9] S. Hanessian, A. Ugolini, D. Dube, A. Glamyan, Can. J. Chem. 1984, 62, 2146.
[10] R. Zemribo, K. T. Mead, Tetrahedron Lett. 1998, 39, 3895.
[11] C. C. Hughes, J. J. Kennedy-Smith, D. Trauner, Org. Lett. 2003, 5, 4113; J. Liu, K. Xu, J. He, L.
Zhang, X. Pan, X. She, J. Org. Chem. 2009, 74, 5063.
[12] B. B. Snider, J. Zhou, Org. Lett. 2006, 8, 1283; L. K. McCaleb, R. L. Halcomb, Org. Lett. 2000, 2,
2631.
[13] S. A. Hermitage, S. M. Roberts, D. J. Watson, Tetrahedron Lett. 1998, 39, 3567.
[14] E. J. Corey, C. J. Helal, Angew. Chem., Int. Ed. 1998, 37, 1986; K. A Parker, M. W. Ledeboer, J. Org.
Chem. 1996, 61, 3214; C. J. Helal, P. A. Magriotis, E. J. Corey, J. Am. Chem. Soc. 1996, 118, 10938.
[15] D. A. Evans, C. W. Downey, J. T. Shaw, J. S. Tedrow, Org. Lett. 2002, 4, 1127.
[16] M. J. Martinelli, N. K. Nayyar, E. D. Moher, U. J. Dhokte, J. M. Pawlak, R.Vaidyanathan, Org. Lett.
1999, 1, 447.
[17] M. Arai, N. Morita, C. Kibayashi, Tetrahedron Lett. 2000, 41, 1199.
[18] J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull. Chem. Soc. Jpn. 1979, 52, 1989; T.
Okino, S. Qi, H. Matsuda, M. Murakami, K. Yamaguchi, J. Nat. Prod. 1997, 60, 158.
Received November 20, 2009