Highly stereoselective synthesis of antitumor agents: Both enantiomers of goniothales diol, altholactone, and isoaltholactone

Article abstract of DOI:10.1016/j.tetasy.2005.08.047

A flexible stereoselective route to synthesize both enantiomers of the highly functionalized substituted tetrahydrofurans and α,β- unsaturated-δ-lactones, goniothales diol, altholactone, and isoaltholactone, from readily available cinnamyl alcohol is described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydroxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in the presence of a catalytic amount of camphor sulfonic acid.

Full text of DOI:10.1016/j.tetasy.2005.08.047

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 3283–3290
Highly stereoselective synthesis of antitumor agents: both
enantiomers of goniothales diol, altholactone, and isoaltholactoneq
Jhillu Singh Yadav,* Atcha Krishnam Raju, Ponugoti Purushothama Rao
and Gurram Rajaiah
Organic Chemistry Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 18 August 2005; accepted 30 August 2005
Abstract—A flexible stereoselective route to synthesize both enantiomers of the highly functionalized substituted tetrahydrofurans
and a,b-unsaturated-d-lactones, goniothales diol, altholactone, and isoaltholactone, from readily available cinnamyl alcohol is
described. This approach derived its asymmetry from Sharpless catalytic asymmetric epoxidation and Sharpless asymmetric dihydr-
oxylation reactions. The resulting diols were produced in high enantiomeric excess and were cyclized in a stereoselective manner in
the presence of a catalytic amount of camphor sulfonic acid.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
detail our synthetic endeavours towards the construction
of (+)-goniothales diol 1a, its enantiomer (ꢀ)-goniot-
hales diol 1b, (+)-altholactone 2a, its enantiomer (ꢀ)-
altholactone 2b, and (+)-isoaltholactone 3a and its
enantiomer (ꢀ)-isoaltholactone 3b employing Sharpless
catalytic asymmetric epoxidation and Sharpless asym-
metric dihydroxylation reactions starting from the inex-
pensive and readily available cinnamyl alcohol. Our
approach is illustrated retrosynthetically in Scheme 1.
Goniothales diol 1a, a substituted tetrahydrofuran, can
be isolated from the bark of the Malaysian tree Gonio-
thalamus borneensis (Annonaceae),1 and has been shown
to have significant cytotoxicity against P388 mouse leu-
kaemia cells, as well as insecticidal activities.1 Altholac-
tone 2a and isoaltholactone 3a, furanopyrones of the
styryllactone family, were isolated from an unknown
Polythea (Annonacae) species,2 and from various Gonio-
thalamous.3 This family of compounds share a common
5-oxygenated-5,6-dihydro-2H-pyran-2-one
structural
2. Results and discussion
motif. Other members of this family include 5-acet-
oxygoniothalamin, goniodiol, etc.4 These natural
products possess anti-tumor,5 anti-fungal,6 and anti-
bacterial properties.6
2.1. Synthesis of (+)-altholactone 2a, (ꢀ)-altholactone 2b,
(+)-isoaltholactone 3a, and (ꢀ)-isoaltholactone 3b
The synthesis began with the Sharpless asymmetric
epoxidation16 of cinnamyl alcohol 7 to afford 6a and
6b in 82% and 83% yields, respectively. Oxidation of
alcohols 6a and 6b using the Swern protocol17 afforded
both aldehydes, which without purification were sub-
jected to Wittig olefination18 with the stable ylide (eth-
oxycarbonylmethylene)triphenylphosphorane to afford
epoxy esters 8a and 8b, respectively, in 87% and 88%
yields (Schemes 2 and 3).
Due to the wide distribution of this class of natural
products in nature, many synthetic methodologies have
been employed to synthesize them.7–14 Most syntheses
use chiral pool starting materials such as sugars, hydroxy
acids, and involve 11–16 steps.
Over the course of our program directed towards the
synthesis of antitumor agents,15 we herein report in
a,b-Unsaturated epoxy ester 8a was subjected to a
Sharpless asymmetric dihydroxylation reaction using
AD-mix-a, to yield 5a and 5b in a ratio of 20:119 (78%
yield) while treatment with AD-mix-b afforded 5a and
q IICT Communication No. 050710.
*
Corresponding author. Tel.: +91 40 27193030; fax: +91 40
27160512; e-mail: yadavpub@iict.res.in
0957-4166/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.08.047

3284
J. S. Yadav et al. / Tetrahedron: Asymmetry 16 (2005) 3283–3290
OH
OH
HO
HO
HO
HO
HO
HO
O
O
O
O
O
O
O
O
Ph
Ph
Ph
COOCH3
Ph
Ph
Ph
O
O
O
COOCH3
O
O
O
1b
2a
1a
2b
3a
3b
OH
HO
OH
O
O
O
1a
or
2a
Ph
OEt
Ph
OH
Ph
COOC2H5
O
OH
6b
5c
4c
Scheme 1.
OH
OH
O
O
O
O
O
a
O
O
d
b, c
OEt
OEt +
Ph
OH
Ph
Ph
OH
OEt
Ph
Ph
(82%)
(87%)
OH
5b
1
5a
20
1
OH
8a
6a
7
1. AD-mix α (78%)
2. AD-mix β (75%)
3. OsO4, NMO (78%)
10
7
13
O
O
O
O
O
i
g,h
OEt
3a
Ph
O
(80%)
(83%)
Ph
O
OEt
HO
OH
HO OH
O
O
9a
e
10a
f
+
OEt
OEt
+
Ph
(94%)
Ph
O
4b
O
O
OTBS
TBSO
Ph
OTBS
OEt
TBSO
4b
4a
O
i
g,k
j
2b
OMe
(83%)
O
O
Ph
(80%)
(97%)
O
12a
11a
Scheme 2. Reagents and conditions: (a) (ꢀ)-DET, Ti(OiPr)4, TBHP, CH2Cl2, ꢀ33 °C; (b) (COCl)2, DMSO, Et3N, CH2Cl2, ꢀ78 °C; (c) Ph3P@CH–
CO2Et, benzene, rt; (d) see Scheme 2; (e) CSA, CH2Cl2, rt; (f) 2,2-DMP, p-TSA, acetone, rt; (g) DIBAL-H, CH2Cl2, ꢀ78 °C; (h) Ph3P@CH–CO2Et,
CH3OH, rt; (i) p-TSA, CH3OH, rt; then benzene, sonication 20–30 min; (j) TBS–Cl, imidazole, DMAP, CH2Cl2, 0 °C to rt; (k) Ph3P@CH–CO2Me,
CH3OH, rt.
5b in a ratio of 1:1019 (75% yield), whilst treatment with
OsO4, NMO afforded 5a and 5b in a 13:7 ratio (78%
yield). The separation of these two isomeric diols 5a
and 5b was not feasible through simple column chroma-
tography because of their close Rf values. It was there-
fore decided to purify the mixture in the subsequent
steps. The mixture of 5a and 5b was subjected to treat-
ment with a catalytic amount of CSA to afford 4a and
4b (94% yield) by cyclization. Subsequent treatment of
this mixture with 2,2-DMP afforded acetonide 9a and
unreacted 4b, which were readily separated by column
chromatography.
phenylphosphorane. Compounds 10a and 12a on treat-
ment with a catalytic amount of p-TSA in methanol
afforded a mixture of diol esters and lactones 3a and 2b.
Removal of methanol by concentration under reduced
pressure and sonication after diluting the residue with
benzene afforded lactones 3a and 2b, respectively (in
83% and 83% yields) (Scheme 2). Epoxy ester 8b was
transformed in a similar fashion to afford 2a and 3b, as
illustrated in Scheme 3.
2.2. Synthesis of (+)-goniothales diol 1a and (ꢀ)-gonio-
thales diol 1b
Ester 9a was reduced to the aldehyde, which was sub-
jected to a Wittig olefination with the stable ylide (ethoxy-
carbonylmethylene)triphenylphosphorane in methanol
as the solvent to yield cis-ester 10a (80% yield, two steps)
predominantly (cis:trans 95:5).20 The trans-diol 4b was
protected with TBSCl to yield 11a in 97% yield. As with
9a, 11a was also reduced with DIBALH to afford an alde-
hyde, which was transformed into the cis-ester 12a (82%
yield, two steps) using (methoxy-carbonylmethylene)tri-
Hydrogenation of esters 12b and 12a was performed
employing Pd (black) in 4.4% HCOOH–MeOH,13 to
afford esters 13a and 13b, respectively (both in 94%
yields). The TBS groups of esters 13a and 13b were
cleanly deprotected using TBAF in dry THF to give a mix-
ture of lactones and diols 1a and 1b, respectively. Removal
of THF under reduced pressure and repeated treatment
with Amberlyst 15 in methanol provided diols 1a and
1b in 74% and 72% yields, respectively (Scheme 4).

J. S. Yadav et al. / Tetrahedron: Asymmetry 16 (2005) 3283–3290
3285
OH
O
OH
O
O
O
O
O
a
O
d
b, c
OEt
+
Ph
OEt
Ph
OH
Ph
OH
OEt
Ph
Ph
(83%)
(88%)
OH
5d
OH
5c
8b
6b
7
1
20
13
10
1
7
1. AD-mix α (75%)
2. AD-mix β (78%)
3. OsO4, NMO (78%)
O
O
O
O
O
i
g,h
OEt
3b
OEt
Ph
O
Ph
O
(82%)
(81%)
O
HO OH
Ph
HO OH
10b
e
+
OEt
9b
f
OEt
+
O
O
Ph
(94%)
O
O
4c
TBSO OTBS
OTBS
O
TBSO
Ph
4d
O
4c
i
g,k
OEt
j
2a
Ph
O
OMe
O
(83%)
(81%)
(97%)
12b
11b
Scheme 3. Reagents and conditions: (a) (+)-DET, Ti(OiPr)4, TBHP, CH2Cl2, ꢀ33 °C; (b) (COCl)2, DMSO, Et3N, CH2Cl2, ꢀ78 °C; (c) Ph3P@CH–
CO2Et, benzene, rt; (d) see Scheme 3; (e) CSA, CH2Cl2, rt; (f) 2,2-DMP, p-TSA, acetone, rt; (g) DIBAL-H, CH2Cl2, ꢀ78 °C; (h) Ph3P@CH–CO2Et,
CH3OH, rt; (i) p-TSA, CH3OH, rt; then benzene, sonication 20–30 min; (j) TBS–Cl, imidazole, DMAP, CH2Cl2, 0 °C to rt; (k) Ph3P@CH–CO2Me,
CH3OH, rt.
TBSO
Ph
OTBS
TBSO
Ph
OTBS
a
O
b
O
1a
OMe
(74 %)
O
(94 %)
O
OMe
13a
12b
OTBS
TBSO
Ph
OTBS
TBSO
Ph
O
a
O
b
OMe
1b
O
(94 %)
O
(72 %)
OMe
12a
13b
Scheme 4. Reagents and conditions: (a) H2/Pd–carbon (10%), 4.4% HCO2H–MeOH, rt; (b) TBAF, THF, 0 °C, then Amberlyst 15, MeOH, 3 h.
3. Conclusion
Infrared (IR) spectra were recorded on Perkin–Elmer
683 spectrometer. Optical rotations were obtained on
Jasco Dip 360 digital polarimeter. Melting points are
uncorrected. NMR spectra were recorded in CDCl3 on
a Varian Gemini 200, Bruker 300, or Varian Unity
400 NMR spectrometers. Chemical shifts (d) are quoted
in parts per million and are referenced to the tetra-
methylsilane (TMS) as the internal standard. Coupling
constants (J) are quoted in Hertz. Column chromato-
graphic separations were carried out on silica gel (60–
120 mesh) and flash chromatographic separations were
carried out using 230–400 mesh size silica gel. Mass
spectra were obtained on Finnegan MAT 1020B or mi-
cro-mass VG 70-70H spectrometer operating at 70 eV
using direct inlet system.
The total syntheses of both enantiomers of goniothales
diol, altholactone, and isoaltholactone were achieved
in efficient yields from readily available cinnamyl alco-
hol 7. The syntheses required only 9 or 10 chemical
operations and were highly stereoselective. Sharpless
asymmetric dihydroxylation reaction of epoxy esters
8a and 8b and CSA catalyzed cyclization of 5a–d are
the key steps of our syntheses. Our route provides a gen-
eral, efficient, and stereoselective access to related substi-
tuted tetrahydrofurans and a,b-unsaturated-d-lactones.
4. Experimental
4.1. General
4.1.1. 3-Phenyl-(2R,3R)-oxiran-2-ylmethanol 6a.
A
mixture of titanium tetraisopropoxide (2.2 g, 7.76
Commercial reagents were used without further purifica-
tion. All solvents were purified by standard techniques.
mmol), (ꢀ)-diethyl D-tartarate (1.84 g, 8.95 mmol), and
˚
4 g of activated powdered 4 A molecular sieves was

3286
J. S. Yadav et al. / Tetrahedron: Asymmetry 16 (2005) 3283–3290
stirred in 200 mL of anhydrous CH2Cl2 at ꢀ23 °C for
30 min. To this mixture was added cinnamyl alcohol 7
(8 g, 59.70 mmol) with 15 mL of CH2Cl2 at ꢀ23 °C.
After the resulting mixture was stirred at ꢀ23 °C for
30 min, the reaction mixture was treated with tert-butyl-
hydroperoxide (49 mL; 3.0 M in toluene) and stirred for
4 h at this temperature. The reaction mixture was
allowed to warm to 0 °C and poured into a freshly pre-
pared and cooled (0 °C) solution of ferrous sulfate and
tartaric acid (10 g and 3 g, respectively) in deionised
water (15 mL). The two-phase mixture was stirred for
25–30 min, aqueous phase separated and extracted with
ether. The combined organic phases were treated with a
precooled (0 °C) solution of 30% NaOH (w/v) in satu-
rated brine. The two-phase mixture was then stirred
for 1 h at room temperature and the aqueous layer sep-
arated. It was treated with ether and the combined
organic extracts dried over Na2SO4 and concentrated
under reduced pressure, resulting in a crude product,
which was purified by flash column chromatography
mixture was stirred for 4 h at rt. After removal of the
solvent, the resulting crude product was purified by flash
column chromatography on silica gel using 20:1 hexane–
EtOAc as eluent to give 6.2 g (87%) of ester 8a as a col-
20
orless liquid: ½aꢁD ¼ þ121:9 (c 1.4, CHCl3); IR (KBr):
1
m = 2983, 1716, 1656, 1263 cmꢀ1; H NMR (200 MHz,
CDCl3): d = 1.30 (3H, t, J = 7.1 Hz), 3.40–3.44 (1H,
m), 3.78–3.80 (1H, m), 4.20 (2H, q, J = 7.1 Hz), 6.15
(1H, dd, J = 15.6, 0.8 Hz), 6.78 (1H, dd, J = 15.5,
6.8 Hz), 7.23–7.26 (5H, m); 13C NMR (CDCl3,
75 MHz): d = 165.4, 143.4, 135.9, 128.5, 125.4, 123.9,
121.1, 60.9, 60.5, 60.4, 14.1; HRMS calcd for
C13H15O3 [M+H]+ 219.1021, found 219.1025.
4.1.4. Ethyl 3-[3-phenyl-(2S,3S)-oxiran-2-yl]-(E)-2-pro-
penoate 8b. Compound 8b was prepared from alcohol
6b in 88% yield employing the same procedure as
explained for the preparation of 8a. Compound 8b (color-
20
less liquid): ½aꢁD ¼ ꢀ136:5 (c 1.6, CHCl3); IR (KBr):
1
m = 2983, 1716, 1656, 1263 cmꢀ1; H NMR (200 MHz,
on silica gel using 17:3 hexane–EtOAc as eluent to give
CDCl3): d = 1.30 (3H, t, J = 7.1 Hz), 3.40–3.44 (1H,
m), 3.78–3.80 (1H, m), 4.20 (2H, q, J = 7.1 Hz), 6.15
(1H, dd, J = 15.6, 0.8 Hz), 6.78 (1H, dd, J = 15.5,
6.8 Hz), 7.23–7.26 (5H, m); 13C NMR (CDCl3,
75 MHz): d = 165.4, 143.4, 135.9, 128.5, 125.4, 123.9,
121.1, 60.9, 60.5, 60.4, 14.1; HRMS calcd for
C13H15O3 [M+H]+ 219.1021, found 219.1025.
20
6a (7.34 g, 82% yield) as liquid; ½aꢁD ¼ þ45:9 (c 1,
EtOH); IR (KBr): m = 3580, 3450, 2980, 1600, 1450,
1380 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d = 2.20
(1H, br s), 3.25–3.33 (1H, m), 3.81 (1H, dd,
J = 5.1 Hz), 3.95 (1H, d, J = 3.0 Hz), 4.18 (1H, dd,
J = 3.1 Hz), 7.20–7.50 (5H, m); 13C NMR (CDCl3,
75 MHz): d = 136.5, 128.3, 128.1, 125.5, 62.5, 61.4,
55.7; HRMS calcd for C9H10O2 [M]+ 150.0681, found
150.0687.
4.1.5. Ethyl (2R,3S)-dihydroxy-3-[3-phenyl-(2R,3R)-oxi-
ran-2-yl]-(2R)-propanoate 5a. To a solution of ester 8a
(1.03 g, 5 mmol) in a 1:1 mixture (30 mL) of water–tert-
butyl alcohol were added sequentially 4.95 g (15 mmol)
of potassium ferricyanide, 2.07 g (15 mmol) of potas-
sium corbonate, and 0.195 g (1.25 mmol) of (DHQ)2-
PHAL, 37 mg (1 mmol) of potassium osmatedihydrate,
and 0.48 g (5 mmol) of methane sulfonamide. The
resulting mixture was stirred at rt for 12 h, and 50 mg
of sodium metabisulfite was then added. After the mix-
ture was stirred for an additional 45 min, it was filtered
through Celite, Florisil, and MgSO4. The filter cake was
thoroughly rinsed with EtOAc–hexane (20:1). The com-
bined filtrates were concentrated and purified by flash
column chromatography on silica gel using 4:6
EtOAc–hexane as eluent to give 0.92 g (78%) of diol
4.1.2. 3-Phenyl-(2S,3S)-oxiran-2-ylmethanol 6b. Com-
pound 6b was prepared from cinnamyl alcohol 7 by
using (+)-diethyl L-tartarate instead of (ꢀ)-diethyl D-
tartarate in 83% yield employing the similar procedure
20
as explained for the preparation of 6a. ½aꢁD ¼ ꢀ50:1 (c
1, CHCl3); IR (KBr): m = 3580, 3450, 2980, 1600,
1450, 1380 cmꢀ1
;
1H NMR (200 MHz, CDCl3):
d = 2.20 (1H, br s), 3.25–3.33 (1H, m), 3.81 (1H,
dd, J = 5.1 Hz), 3.95 (1H, d, J = 3.0 Hz), 4.18 (1H, dd,
J = 3.1 Hz), 7.20–7.50 (5H, m); 13C NMR (CDCl3,
75 MHz): d = 136.5, 128.3, 128.1, 125.5, 62.5, 61.4,
55.7; HRMS calcd for C9H10O2 [M]+ 150.0681, found
150.0687.
5a as
a semi-solid. Compound 5a (semi-solid):
20
4.1.3. Ethyl 3-[3-phenyl-(2R,3R)-oxiran-2-yl]-(E)-2-pro-
penoate 8a. Oxalyl chloride (8.4 g, 66.66 mmol) in
CH2Cl2 (100 mL) was cooled to ꢀ78 °C and DMSO
(7.8 g, 99.99 mmol) in CH2Cl2 (15 mL) added via can-
nula. The reaction mixture was stirred at ꢀ78 °C for
1 h before a solution of alcohol 6a (5 g, 33.33 mmol)
in CH2Cl2 (10 mL) was added dropwise via cannula.
The reaction mixture was stirred for 30 min at which
point triethylamine (32.3 mL, 233.33 mmol) was added
dropwise over 10 min. The reaction mixture was stirred
at ꢀ78 °C for 15 min and then warmed to 0 °C. This was
stirred for 5 min at 0 °C and then quenched by the addi-
tion of 0.5 M sodium bisulfate. The organic extracts
were washed with water, brine, dried over anhydrous
sodium sulfate, and concentrated to give the crude alde-
hyde, which was taken in dry benzene (100 mL) after
½aꢁD ¼ þ45:7 (c 1, CHCl3); IR (KBr): m = 3474, 2983,
1738, 1376, 1217 cmꢀ1; H NMR (200 MHz, CDCl3):
1
d = 1.32 (3H, t, J = 7.2 Hz), 2.71 (1H, br s), 3.13–3.17
(1H, m), 3.32 (1H, br s), 3.89–3.92 (3H, m), 4.28 (2H,
q, J = 7.2 Hz), 7.23–7.29 (5H, m); 13C NMR (CDCl3,
75 MHz): d = 172.5, 136.4, 128.3, 127.7, 125.6, 79.9,
72.5, 71.7, 62.1, 55.0, 13.9; HRMS calcd for
C13H16O5Na [M+Na]+ 275.0895, found 275.0906.
4.1.6. Ethyl (2S,3R)-dihydroxy-3-[3-phenyl-(2R,3R)-oxi-
ran-2-yl]-(2S)-propanoate 5b. Compound 5b was pre-
pared from ester 8a by using (DHQD)2-PHAL instead
of (DHQ)2-PHAL in 75% yield employing the similar
procedure as explained for the preparation of 5a. Com-
20
pound 5b (semi-solid): ½aꢁD ¼ þ43:5 (c 1.8, CHCl3); IR
(KBr): m = 3455, 2980, 1731, 1368, 1221 cmꢀ1
;
1H
which
(ethoxycarbonylmethylene)triphenyl-phospho-
NMR (200 MHz, CDCl3): d = 1.32 (3H, t, J = 6.5 Hz),
rane (12.6 g, 36.41 mmol) was added. The reaction
2.60 (1H, br s), 3.12–3.29 (2H, m), 3.85–3.93 (1H, m),

J. S. Yadav et al. / Tetrahedron: Asymmetry 16 (2005) 3283–3290
3287
4.10–4.19 (1H, m), 4.23–4.42 (3H, m), 7.23–7.39 (5H,
m); 13C NMR (CDCl3, 75 MHz): d = 172.3, 136.1,
128.1, 127.1, 125.3, 83.8, 72.1, 71.4, 62.0, 57.1, 13.8;
HRMS calcd for C13H16O5Na [M+Na]+ 275.0895,
found 275.0906.
(3H, t, J = 6.9 Hz), 2.72–3.01 (2H, m), 4.03–4.16 (1H,
m), 4.20–4.40 (3H, m), 4.61–4.71 (2H, m), 7.22–7.60
(5H, m); 13C NMR (CDCl3, 75 MHz): d = 170.3,
138.9, 128.4, 128.0, 126.3, 85.3, 82.5, 79.5, 78.2, 61.5,
14.1; HRMS calcd for C13H16O5Na [M+Na]+
275.0895, found 275.0906.
4.1.7. Ethyl (2R,3S)-dihydroxy-3-[3-phenyl-(2S,3S)-oxi-
ran-2-yl]-(2R)-propanoate 5c. Compound 5c was pre-
pared from ester 8b in 75% yield employing a similar
4.1.11. Ethyl 3,4-dihydroxy-5-phenyl-(2R,3S,4R,5R)-
tetrahydro-2-furancarboxylate 4c. Compound 4c was
prepared from diol 5c in 78% yield employing the same
procedure as explained for the preparation of 4a. Com-
procedure as explained for the preparation of 5a. Com-
20
pound 5c (semi-solid): ½aꢁD ¼ ꢀ45:7 (c 1, CHCl3); IR
(KBr): m = 3455, 2980, 1731, 1368, 1221 cmꢀ1
;
1H
pound 4c (colorless needles): mp 98–100 °C;
20
NMR (200 MHz, CDCl3): d = 1.32 (3H, t, J = 6.5 Hz),
2.60 (1H, br s), 3.12–3.29 (2H, m), 3.85–3.93 (1H, m),
4.10–4.19 (1H, m), 4.23–4.42 (3H, m), 7.23–7.39 (5H,
m); 13C NMR (CDCl3, 75 MHz): d = 172.3, 136.1,
128.1, 127.1, 125.3, 83.8, 72.1, 71.4, 62.0, 57.1, 13.8;
HRMS calcd for C13H16O5Na [M+Na]+ 275.0895,
found 275.0906.
½aꢁD ¼ þ24:5 (c 1, CHCl3); IR (KBr): m = 3419, 2933,
1
1748, 1452, 1383 cmꢀ1; H NMR (200 MHz, CDCl3):
d = 1.33 (3H, t, J = 6.9 Hz), 2.72–3.01 (2H, m), 4.03–
4.16 (1H, m), 4.20–4.40 (3H, m), 4.61–4.71 (2H, m),
7.22–7.60 (5H, m); 13C NMR (CDCl3, 75 MHz):
d = 170.3, 138.9, 128.4, 128.0, 126.3, 85.3, 82.5, 79.5,
78.2, 61.5, 14.1; HRMS calcd for C13H16O5Na
[M+Na]+ 275. 0895, found 275.0906.
4.1.8. Ethyl (2S,3R)-dihydroxy-3-[3-phenyl-(2S,3S)-oxi-
ran-2-yl]-(2S)-propanoate 5d. Compound 5d was pre-
pared from ester 8b by using (DHQD)2-PHAL instead
of (DHQ)2-PHAL in 78% yield employing the similar
4.1.12. Ethyl 3,4-dihydroxy-5-phenyl-(2S,3R,4R,5R)-
tetrahydro-2-furancarboxylate 4d. Compound 4d was
prepared from diol 5d in 78% yield employing the same
procedure as explained for the preparation of 5a. Com-
procedure as explained for the preparation of 4a. Com-
20
20
pound 5d (semi-solid): ½aꢁD ¼ ꢀ55:3 (c 1, CHCl3); IR
pound 4d (semi-solid): ½aꢁD ¼ þ15:5 (c 1.4, CHCl3); IR
(KBr): m = 3474, 2983, 1738, 1376, 1217 cmꢀ1
;
1H
(KBr): m = 3357, 2928, 1759, 1713, 1452, 1372 cmꢀ1
;
NMR (200 MHz, CDCl3): d = 1.32 (3H, t, J = 7.2 Hz),
2.71 (1H, br s), 3.13–3.17 (1H, m), 3.32 (1H, br s),
3.89–3.92 (3H, m), 4.28 (2H, q, J = 7.2 Hz), 7.23–7.29
(5H, m); 13C NMR (CDCl3, 75 MHz): d = 172.5,
136.4, 128.3, 127.7, 125.6, 79.9, 72.5, 71.7, 62.1, 55.0,
13.9; HRMS calcd for C13H16O5Na [M+Na]+
275.0895, found 275.0906.
1H NMR (200 MHz, CDCl3): d = 1.34 (3H, t,
J = 6.6 Hz), 3.23–3.48 (2H, m), 3.92–4.02 (1H, m),
4.28 (2H, q, J = 6.6 Hz), 4.43–4.53 (1H, m), 4.80 (1H,
d, J = 5.9 Hz), 5.02 (1H, d, J = 5.9 Hz), 7.25–7.34 (5H,
m); 13C NMR (CDCl3, 75 MHz): d = 171.0, 139.2,
128.9, 128.0, 125.8, 83.9, 80.2, 78.1, 72.1, 61.6, 14.1;
HRMS calcd for C13H16O5Na [M+Na]+ 275.0895,
found 275.0906.
4.1.9. Ethyl 3,4-dihydroxy-5-phenyl-(2R,3S,4S,5S)-tetra-
hydro-2-furancarboxylate 4a. Diol 5a (1 g, 3.96 mmol)
was taken in CH2Cl2 (20 mL) to which was added a cat-
alytic amount of camphor sulfonic acid at 0 °C. The
reaction mixture was stirred for 3–4 h and neutralized
with saturated aqueous NaHCO3, the solvent was then
removed under reduced pressure. The crude residue
was purified by column chromatography using
EtOAc–hexane (1:1) as eluent to afford 4a (0.94 g,
4.1.13. Ethyl 2,2-dimethyl-6-phenyl-(3aS,4R,6S,6aS)-per-
hydrofuro[3,4-d][1,3]dioxole-4-carboxylate 9a. A mix-
ture of 4a (2 g, 79.36 mmol), 2,2-dimethoxy propane
(0.9 g, 87.30 mmol), and a catalytic amount of p-TSA
in acetone (30 mL) was stirred for 2 h, neutralized with
saturated aqueous NaHCO3 and then concentrated.
The residue was purified by silica gel column chroma-
tography (EtOAc–hexane 1:20) to give 9a (2.2 g, 97%)
20
94%) as semi-solid. Compound 4a (semi-solid):
as a liquid: 9a (viscous liquid): ½aꢁD ¼ þ17:5 (c 1.8,
20
½aꢁD ¼ ꢀ14:5 (c 1.8, CHCl3); IR (KBr): m = 3357,
CHCl3); IR (KBr): m = 2986, 1761, 1453, 1378, 1207,
2928, 1759, 1713, 1452, 1372 cmꢀ1
;
1H NMR
1107 cmꢀ1 1H NMR (200 MHz, CDCl3): d = 1.32
;
(200 MHz, CDCl3): d = 1.34 (3H, t, J = 6.6 Hz), 3.23–
3.48 (2H, m), 3.92–4.02 (1H, m), 4.28 (2H, q,
J = 6.6 Hz), 4.43–4.53 (1H, m), 4.80 (1H, d,
J = 5.9 Hz), 5.02 (1H, d, J = 5.9 Hz), 7.25–7.34 (5H,
m); 13C NMR (CDCl3, 75 MHz): d = 171.0, 139.2,
128.9, 128.0, 125.8, 83.9, 80.2, 78.1, 72.1, 61.6, 14.1;
HRMS calcd for C13H16O5Na [M+Na]+ 275.0895,
found 275.0906.
(3H, t, J = 7.4 Hz), 1.33 (3H, s), 1.52 (3H, s), 4.25
(2H, q, J = 7.4 Hz), 4.55 (1H, dd, J = 5.2, 0.7 Hz),
4.80–4.98 (2H, m), 5.33 (1H, s), 7.25–7.32 (5H, m); 13C
NMR (CDCl3, 75 MHz): d = 167.8, 137.6, 128.6,
127.7, 125.5, 113.8, 86.3, 85.1, 81.8, 80.1, 61.0, 26.2,
25.2, 14.2; HRMS calcd for C16H21O5 [M+H]+
293.1389, found 293.1392.
4.1.14. Ethyl 2,2-dimethyl-6-phenyl-(3aR,4S,6R,6aR)-
perhydrofuro[3,4-d][1,3]dioxole-4-carboxylate 9b. Com-
pound 9b was prepared from compound 4d in 94% yield
employing the same procedure as explained for the prep-
4.1.10. Ethyl 3,4-dihydroxy-5-phenyl-(2S,3R,4S,5S)-
tetrahydro-2-furancarboxylate 4b. Compound 4b was
prepared from diol 5b in 94% yield employing the same
procedure as explained for the preparation of 4a. Com-
aration of 4a. Compound 9b (viscous liquid):
20
20
pound 4b (colorless needles): mp 98 °C; ½aꢁD ¼ ꢀ22:5 (c
½aꢁD ¼ ꢀ19:5 (c 1.1, CHCl3); IR (KBr): m = 2986,
1.9, CHCl3); IR (KBr): m = 3419, 2933, 1748, 1452,
1761, 1453, 1378, 1207, 1107 cmꢀ1
;
1H NMR
1383 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d = 1.33
(200 MHz, CDCl3): d = 1.32 (3H, t, J = 7.4 Hz), 1.33

3288
J. S. Yadav et al. / Tetrahedron: Asymmetry 16 (2005) 3283–3290
(3H, s), 1.52 (3H, s), 4.25 (2H, q, J = 7.4 Hz), 4.55 (1H,
dd, J = 5.2, 0.7 Hz), 4.80–4.98 (2H, m), 5.33 (1H, s),
7.25–7.32 (5H, m); 13C NMR (CDCl3, 75 MHz):
d = 167.8, 137.6, 128.6, 127.7, 125.5, 113.8, 86.3, 85.1,
81.8, 80.1, 61.0, 26.2, 25.2, 14.2; HRMS calcd for
C16H21O5 [M+H]+ 293.1389, found 293.1392.
sure. Purification of the residue by column chromatog-
raphy (silica gel, EtOAc–hexane 1:20 as eluent) gave
11a (3.6 g, 97%) as a colorless clear oil: 11a (viscous
20
liquid): ½aꢁD ¼ þ19:2 (c 1.8, CHCl3); IR (KBr):
m = 2934, 1737, 1467, 1256, 1095 cmꢀ1
;
1H NMR
(200 MHz, CDCl3): d = ꢀ0.10 (3H, s), 0.01 (3H, s),
0.10 (3H, s), 0.20 (3H, s), 0.72 (9H, s), 0.92 (9H, s),
1.45 (3H, t, J = 7.2 Hz), 4.12–4.25 (3H, m), 4.30–4.41
(1H, m), 4.71–4.79 (1H, m), 4.90 (1H, s), 7.15–7.29
(2H, m), 7.45–7.56 (3H, m); 13C NMR (CDCl3,
75 MHz): d = 169.5, 140.2, 127.9, 127.1, 126.4, 89.3,
83.8, 82.0, 80.1, 60.9, 25.6, 25.3, 17.6, 14.1, ꢀ4.4, ꢀ4.5,
ꢀ4.8, ꢀ5.3; HRMS calcd for C25H45O5Si2 [M+H]+
481.2805, found 481.2811.
4.1.15. Ethyl 3-[2,2-dimethyl-6-phenyl-(3aR,4S,6S,6aS)-
perhydrofuro[3,4-d][1,3]dioxol-4-yl]-(Z)-2-propenoate 10a.
To a solution of ester 9a (2 g, 6.84 mmol) in CH2Cl2
(50 mL) at ꢀ78 °C was added DIBAL-H (1.01 M solu-
tion in hexane, 3.5 mL, 6.84 mmol). After being stirred
at ꢀ78 °C for 2 h, the reaction was quenched with satu-
rated aqueous potassium sodium tartarate. The resul-
tant mixture was diluted with ethyl acetate and stirred
vigorously at room temperature until the layers became
clear. The organic layer was separated and washed with
brine, dried over Na2SO4, filtered, and concentrated
under reduced pressure to give the crude aldehyde, which
was treated with (ethoxycarbonyl-methylene)triphenyl-
phosphorane (2.3 g, 6.81 mmol) in dry methanol
(50 mL). The reaction mixture was stirred at rt for 6–
8 h. After removal of the solvent, the resulting crude
product was purified by flash column chromatography
on silica gel using 20:1 hexane–EtOAc as eluent to give
4.1.18. Methyl 3,4-di-tert-butyldimethylsilanyloxy-5-phen-
11b.
yl-(2R,3S,4R,5R)-tetrahydro-2-furancarboxylate
Compound 11b was prepared from compound 4a
in 97% yield employing the same procedure as
explained for the preparation of 11a. Compound 11b
20
(viscous liquid): ½aꢁD ¼ ꢀ16:2 (c 1, CHCl3); IR (KBr):
m = 2934, 1737, 1467, 1256, 1095 cmꢀ1
;
1H NMR
(200 MHz, CDCl3): d = ꢀ0.10 (3H, s), 0.01 (3H, s),
0.10 (3H, s), 0.20 (3H, s), 0.72 (9H, s), 0.92 (9H, s),
1.45 (3H, t, J = 7.2 Hz), 4.12–4.25 (3H, m), 4.30–4.41
(1H, m), 4.71–4.79 (1H, m), 4.90 (1H, s), 7.15–7.29
(2H, m), 7.45–7.56 (3H, m); 13C NMR (CDCl3,
75 MHz): d = 169.5, 140.2, 127.9, 127.1, 126.4, 89.3,
83.8, 82.0, 80.1, 60.9, 25.6: m/z, 25.3, 17.6, 14.1, ꢀ4.4,
ꢀ4.5, ꢀ4.8, ꢀ5.3; HRMS calcd for C25H45O5Si2
[M+H]+ 481.2805, found 481.2811.
1.72 g (80%) of ester 10a as a colorless viscous liquid.
20
Compound 10a (viscous liquid): ½aꢁD ¼ þ97:3 (c 1.5,
CHCl3); IR (KBr): m = 2985, 1716, 1651, 1382,
1195 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d = 1.29
(3H, t, J = 7.4 Hz), 1.34 (3H, s), 1.55 (3H, s), 4.15
(2H, q, J = 7.4 Hz), 4.93–5.03 (2H, m), 5.21 (1H, s),
5.34–5.42 (1H, m), 5.95 (1H, dd, J = 11.8, 1.4 Hz),
6.42 (1H, dd, J = 11.8, 6.7 Hz), 7.21–7.36 (5H, m); 13C
NMR (CDCl3, 75 MHz): d = 165.5, 145.4, 138.5,
128.5, 127.3, 125.4, 120.8, 112.6, 87.3, 85.0, 82.9, 78.1,
60.2, 26.3, 24.9, 14.1; HRMS calcd for C18H23O5
[M+H]+ 319.1545, found 319.1546.
4.1.19. Methyl 3-[3,4-di-tert-butyldimethylsilanyloxy-5-
phenyl-(2R,3S,4S,5S)-tetrahydro-2-furanyl]-(Z)-2-propeno-
ate 12a. Compound 12a was prepared from ester 11a
by using (methoxycarbonylmethylene)triphenylphos-
phorane instead of (ethoxycarbonylmethylene)triphen-
ylphosphorane in 80% yield and employing the
4.1.16. Ethyl 3-[2,2-dimethyl-6-phenyl-(3aS,4R,6R,6aR)-
perhydrofuro[3,4-d][1,3]dioxol-4-yl]-(Z)-2-propenoate 10b.
.Compound 10b was prepared from compound 9b in 81%
yield employing the same procedure as explained for
similar procedure as explained for the preparation of
20
10a. Compound 12a (viscous liquid): ½aꢁD ¼ ꢀ96:3 (c
1.0, CHCl3); IR (KBr): m = 2954, 1742, 1467, 1363,
1256 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d = ꢀ0.20
the preparation of 10a. Compound 10b (viscous liquid):
(3H, s), ꢀ0.09 (3H, s), 0.01 (3H, s), 0.10 (3H, s), 0.72
(9H, s), 0.92 (9H, s), 3.71 (3H, s), 4.01–4.09 (1H, m),
4.23–4.30 (1H, m), 4.75 (1H, s), 5.45–5.55 (1H, m),
5.91 (1H, dd, J = 12, 1.6 Hz), 6.50 (1H, dd, J = 12,
6.4 Hz), 7.15–7.41 (5H, m); 13C NMR (CDCl3,
75 MHz): d = 147.3, 130.1, 128.0, 127.1, 126.6, 120.5,
109.7, 89.9, 85.8, 81.4, 80.0, 54.3, 51.3, 32.3, 25.7, 7.9,
ꢀ4.4, ꢀ4.5, ꢀ4.7, ꢀ5.1; HRMS calcd for C26H45O5Si2
[M+H]+ 493.2805, found 493.2825.
20
½aꢁD ¼ ꢀ92:1 (c 2, CHCl3); IR (KBr): m = 2985, 1716,
1
1651, 1382, 1195 cmꢀ1; H NMR (200 MHz, CDCl3):
d = 1.29 (3H, t, J = 7.4 Hz), 1.34 (3H, s), 1.55 (3H, s),
4.15 (2H, q, J = 7.4 Hz), 4.93–5.03 (2H, m), 5.21 (1H,
s), 5.34–5.42 (1H, m), 5.95 (1H, dd, J = 11.8, 1.4 Hz),
6.42 (1H, dd, J = 11.8, 6.7 Hz), 7.21–7.36 (5H, m); 13C
NMR (CDCl3, 75 MHz): d = 165.5, 145.4, 138.5,
128.5, 127.3, 125.4, 120.8, 112.6, 87.3, 85.0, 82.9, 78.1,
60.2, 26.3, 24.9, 14.1; HRMS calcd for C18H23O5
[M+H]+ 318.1545, found 319.1546.
4.1.20. Methyl 3-[3,4-di-tert-butyldimethylsilanyloxy-5-
phenyl-(2S,3R,4R,5R)-tetra-hydro-2-furanyl]-(Z)-2-pro-
penoate 12b. Compound 12b was prepared from ester
11b by using (methoxycarbonylmethylene)triphenyl-
phosphorane instead of (ethoxycarbonylmethylene)tri-
phenylphosphorane in 81% yield and employing
4.1.17. Methyl 3,4-di-tert-butyldimethylsilanyloxy-5-phen-
yl-(2S,3R,4S,5S)-tetrahydro-2-furancarboxylate
11a.
To a solution of 4b (2 g, 7.93 mmol) in anhydrous
CH2Cl2 (80 mL) were added tert-butylchlorodimethyl-
silane (2.6 g, 17.46 mmol) and imidazole (1.3 g,
19.84 mmol) at 0 °C. After being stirred for 4 h, the
reaction mixture was diluted with ethyl acetate, washed
with saturated aqueous NH4Cl, brine, dried over
Na2SO4, filtered, and concentrated under reduced pres-
the similar procedure as explained for the preparation
20
of 10a. Compound 12b (viscous liquid): ½aꢁD
¼
þ103:1 (c 1, CHCl3); IR (KBr): m = 2954, 1742, 1467,
1363, 1256 cmꢀ1 1H NMR (200 MHz, CDCl3):
d = ꢀ0.20 (3H, s), ꢀ0.09 (3H, s), 0.01 (3H, s), 0.10
;

J. S. Yadav et al. / Tetrahedron: Asymmetry 16 (2005) 3283–3290
3289
20
(3H, s), 0.72 (9H, s), 0.92 (9H, s), 3.71 (3H, s), 4.01–
4.09 (1H, m), 4.23–4.30 (1H, m), 4.75 (1H, s), 5.45–
5.55 (1H, m), 5.91 (1H, dd, J = 12, 1.6 Hz), 6.50 (1H,
dd, J = 12, 6.4 Hz), 7.15–7.41 (5H, m); 13C NMR
(CDCl3, 75 MHz): d = 147.3, 130.1, 128.0, 127.1,
126.6, 120.5, 109.7, 89.9, 85.8, 81.4, 80.0, 54.3, 51.3,
32.3, 25.7, 7.9, ꢀ4.4, ꢀ4.5, ꢀ4.7, ꢀ5.1; HRMS calcd
for C26H45O5Si2 [M+H]+ 493.2805, found 493.2825.
3b (colorless oily material): ½aꢁD ¼ ꢀ32:2 (c 0.30,
EtOH); IR (KBr): m = 3500, 3030, 1730, 1645 cmꢀ1; H
1
NMR (200 MHz, CDCl3): d = 3.31 (1H, br s), 4.26–
4.29 (1H, m) 4.78 (1H, d, J = 7.5 Hz), 4.86 (1H, t,
J = 5.5, 4.4 Hz), 5.05 (1H, t, J = 5.7 Hz), 6.20 (1H, dd,
J = 10.0, 0.7 Hz), 6.85 (1H, dd, J = 9.9, 4.5 Hz), 7.25–
7.40 (5H, m). 13C NMR (CDCl3, 75 MHz): d = 161.9,
141.7, 138.6, 128.5, 128.1, 125.6, 122.4, 83.1, 78.6,
78.4, 67.7; HRMS calcd for C13H13O4 [M+H]+
233.0814, found 233.0815.
4.1.21. (+)-Isoaltholactone 3a. A solution of com-
pound 10a (0.1 g, 0.431 mmol) in methanol (15 mL)
was treated with a catalytic amount of p-TSA at rt to
afford a mixture of diol ester and lactone 3a. Removal
of methanol by concentration under reduced pressure
and sonication after diluting the residue with benzene
(20 mL) afforded the crude lactone 3a. The crude prod-
uct was purified by flash column chromatography on sil-
ica gel using 1:1 hexane–EtOAc as eluent to give 60 mg
4.1.25. Methyl-3-[3,4-di-tert-butyldimethylsilanyloxy-5-
phenyl-(2S,3R,4R,5R)-tetra-hydro-2-furanyl]propanoate
13a. Compound 12b (0.5 g, 1.01 mmol) was treated
with 10% of Pd/C (10 mg) in 4.4% HCOOH–MeOH
under a hydrogen atmosphere at room temperature for
3 h, and filtered through Celite. The filter cake was washed
twice with ethyl acetate. The solvent was removed in
vacuo to provide the crude compound, which was puri-
fied by column chromatography on silica gel using 20:1
(83%) of 3a as colorless needles: mp 102–103 °C (lit.3b
20
mp 103.5–104.5 °C); ½aꢁD ¼ þ34:5 (c 0.50, EtOH) {lit.3b
20
½aꢁD ¼ þ32 (c 0.013, EtOH)}; IR (KBr): m = 3500, 3030,
hexane–EtOAc as eluent to give 0.47 g (94%) of 13a as
20
1730, 1645 cmꢀ1; 1H NMR (200 MHz, CDCl3): d = 3.31
(1H, br s), 4.26–4.29 (1H, m) 4.78 (1H, d, J = 7.5 Hz),
4.86 (1H, t, J = 5.5, 4.4 Hz), 5.05 (1H, t, J = 5.7 Hz),
6.20 (1H, dd, J = 10.0, 0.7 Hz), 6.85 (1H, dd, J = 9.9,
4.5 Hz), 7.25–7.40 (5H, m). 13C NMR (CDCl3,
75 MHz): d = 161.9, 141.7, 138.6, 128.5, 128.1, 125.6,
122.4, 83.1, 78.6, 78.4, 67.7; HRMS calcd for
C13H13O4 [M+H]+ 233.0814, found 233.0815.
colorless liquid: ½aꢁD ¼ þ18:2 (c 1, CHCl3); IR (KBr):
m = 2954, 1742, 1465, 1359, 1256 cmꢀ1
;
1H NMR
(200 MHz, CDCl3): d = ꢀ0.18 (3H, s), 0.01 (3H, s),
0.04 (3H, s), 0.10 (3H, s), 0.78 (9H, s), 0.91 (9H, s),
1.82–1.95 (1H, m) 2.05–2.18 (1H, m), 2.40–2.61 (2H,
m), 3.63 (3H, s), 3.81–3.85 (1H, m), 3.93–3.97 (1H, m),
4.03–4.14 (1H, m), 4.62 (1H, s), 7.10–7.39 (5H, m); 13C
NMR (CDCl3, 75 MHz): d = 173.9, 140.9, 127.9,
127.0, 126.6, 88.8, 85.4, 81.0, 79.9, 51.5, 31.0, 25.7,
25.6, 24.6, 17.8, ꢀ4.5, ꢀ5.0; HRMS calcd for
C26H47O5Si2 [M+H]+ 495.2962, found 495.2975.
4.1.22. (ꢀ)-Altholactone 2b. Lactone 2b was prepared
from 12a in 83% yield employing the same procedure
as explained for the preparation of 3a. Compound 2b
20
(colorless oily material): ½aꢁD ¼ ꢀ163:9 (c 0.25, EtOH)
4.1.26. Methyl 3-[3,4-di-tert-butyldimethylsilanyloxy-
5-phenyl-(2R,3S,4S,5S)-tetrahydro-2-furanyl]propanoate
13b. Compound 13b was prepared from 12a in 94%
{lit.9a [a]D = ꢀ166 (c 0.50, EtOH)}; IR (KBr):
m = 3418, 2925, 1731 cmꢀ1
;
1H NMR (200 MHz,
CDCl3): d = 3.79–4.01 (1H, m), 4.44 (1H, dd, J = 5.6,
2.3 Hz), 4.63 (1H, t, J = 5.1 Hz), 4.73 (1H, d,
J = 5.5 Hz), 4.92 (1H, dd, J = 5.1, 2.2 Hz), 6.21 (1H,
d, J = 9.9 Hz), 6.95 (1H, dd, J = 9.9, 4.8 Hz), 7.26–
7.38 (5H, m). 13C NMR (CDCl3, 75 MHz): d = 161.9,
140.7, 138.3, 128.5, 128.1, 126.2, 123.5, 86.5, 86.1,
83.4, 68.1; HRMS calcd for C13H13O4 [M+H]+
233.0814, found 233.0808.
yield employing the same procedure as explained for
20
the preparation of 13a. Compound 13b: ½aꢁD ¼ ꢀ18:9
(c 1, CHCl3); IR (KBr): m = 2954, 1742, 1465, 1359,
1256 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d = ꢀ0.18
(3H, s), 0.01 (3H, s), 0.04 (3H, s), 0.10 (3H, s), 0.78
(9H, s), 0.91 (9H, s), 1.82–1.95 (1H, m) 2.05–2.18 (1H,
m), 2.40–2.61 (2H, m), 3.63 (3H, s), 3.81–3.85 (1H, m),
3.93–3.97 (1H, m), 4.03–4.14 (1H, m), 4.62 (1H, s),
7.10–7.39 (5H, m); 13C NMR (CDCl3, 75 MHz):
d = 173.9, 140.9, 127.9, 127.0, 126.6, 88.8, 85.4, 81.0,
79.9, 51.5, 31.0, 25.7, 25.6, 24.6, 17.8, ꢀ4.5, ꢀ5.0;
HRMS calcd for C26H47O5Si2 [M+H]+ 495.2962, found
495.2975.
4.1.23. (+)-Altholactone 2a. Lactone 2a was prepared
from 12b in 83% yield employing the same procedure
as explained for the preparation of 3a. Compound 2a
(colorless needles): mp 108–109 °C (lit.3a mp 110 °C);
20
½aꢁD ¼ þ183:1 (c 0.20, EtOH) {lit.2 [a]D = +188, lit.3a
[a]D = +184.7}; IR (KBr): m = 3418, 2925, 1731 cmꢀ1
;
4.1.27. (+)-Goniothales diol 1a. To a stirred solution of
compound 13a (0.3 g, 0.60 mmol) in dry THF was
added TBAF (0.33 g, 12.75 mmol) in THF (5 mL) at
room temperature. The reaction mixture was stirred
for 2 h at room temperature. The reaction was then
quenched with Et2O and saturated aqueous NaHCO3.
The two phases were separated and the aqueous layer
extracted with Et2O. The combined organic fractions
were dried over Na2SO4, and concentrated to give a res-
idue, which was treated with Amberlyst 15 in methanol
1H NMR (200 MHz, CDCl3): d = 3.79–4.01 (1H, m),
4.44 (1H, dd, J = 5.6, 2.3 Hz), 4.63 (1H, t, J = 5.1 Hz),
4.73 (1H, d, J = 5.5 Hz), 4.92 (1H, dd, J = 5.1,
2.2 Hz), 6.21 (1H, d, J = 9.9 Hz), 6.95 (1H, dd,
J = 9.9, 4.8 Hz), 7.26–7.38 (5H, m). 13C NMR (CDCl3,
75 MHz): d = 161.9, 140.7, 138.3, 128.5, 128.1, 126.2,
123.5, 86.5, 86.1, 83.4, 68.1; HRMS calcd for
C13H13O4 [M+H]+ 233. 0814, found 233.0808.
4.1.24. (ꢀ)-Isoaltholactone 3b. Compound 3b was pre-
pared from 10b in 82% yield employing the same proce-
dure as explained for the preparation of 3a. Compound
to provide the target compound 1a in 74% (0.11 g) yield:
20
1a (yellow oil): ½aꢁD ¼ þ6:9 (c 0.7, EtOH) {lit.1
25
½aꢁD ¼ þ7:5 (c 0.23, EtOH)}; IR (KBr): m = 3443,

3290
J. S. Yadav et al. / Tetrahedron: Asymmetry 16 (2005) 3283–3290
2951, 2919, 1742, 1451, 1374, 1219, 1165 cmꢀ1 1H
;
5. Blazques, M. A.; Bermejo, A.; Zafra-Polo, M. C.; Cortes,
D. Phytochem. Anal. 1999, 10, 161.
NMR (200 MHz, CDCl3): d = 2.01–2.12 (2H, m),
2.42–2.62 (2H, m), 3.65 (3H, s), 3.97–4.07 (3H, m),
4.59 (1H, d, J = 4.5 Hz), 7.25 (1H, d, J = 7.0 Hz), 7.33
(2H, t, J = 7.0 Hz), 7.41 (2H, d, J = 7.0 Hz); 13C
NMR (CDCl3, 75 MHz): d = 174.9, 139.8, 128.7,
127.9, 126.3, 86.1, 85.3, 80.7, 79.0, 51.9, 30.6, 23.7;
HRMS calcd for C14H18O5Na [M+Na]+ 289.1051,
found 289.1059.
6. For a review of 5,6-dihydro-2H-pyran-2-ones, see: Davies-
Coleman, M. T.; Rivett, D. E. A.. In Herz, W., Grisebach,
H., Kirby, G. W., Tamm, Ch., Eds.; Progress in the
Chemistry of Organic Natural Products; Springer: New
York, 1989; Vol. 55, pp 1–35.
7. (a) Peng, X.; Li, A.; Lu, J.; Wang, Q.; Pan, X.; Chan, X. S.
C. Tetrahedron 2002, 58, 6799; (b) Harris, J. M.; OÕDoh-
erty, G. A. Tetrahedron 2001, 57, 5161, and references
cited therein.
8. (a) Tsubuki, M.; Kanai, K.; Honda, T. Synlett 1993, 653;
(b) Tsubuki, M.; Kanai, K.; Nagase, H.; Honda, T.
Tetrahedron 1999, 55, 2493.
4.1.28. (ꢀ)-Goniothales diol 1b. Compound 1b was pre-
pared from diol 13b in 74% yield employing the same
procedure as explained for the preparation of 1a. Com-
20
9. (a) Gesson, J.-P.; Jacquesy, J.-C.; Mondon, M. Tetra-
hedron Lett. 1987, 28, 3945; (b) Gesson, J.-P.; Jacquesy,
J.-C.; Mondon, M. Tetrahedron Lett. 1987, 28, 3949; (c)
Gesson, J.-P.; Jacquesy, J.-C.; Mondon, M. Tetrahedron
1989, 45, 2627; (d) Gillhouley, J. G.; Shing, T. K. M. J.
Chem. Soc., Chem. Commun. 1988, 976; (e) Shing, T. K.
M.; Gillhouley, J. G. Tetrahedron 1994, 50, 8685; (f)
Shing, T. K. M.; Tsui, H.-C.; Zhou, Z.-H. J. Org. Chem.
1995, 60, 3121; (g) Ueno, Y.; Tadano, K.; Ogawa, S.;
McLaughlin, J. L.; Alkofahi, A. Bull. Chem. Soc. Jpn.
1989, 62, 2338; (h) Haratate, A.; Kiyota, H.; Oritani, T. J.
Pesticide Sci. 2001, 26, 366; (i) Kang, S. H.; Kim, W. J.
Tetrahedron Lett. 1989, 30, 5915.
pound 1b (yellow oil): ½aꢁD ¼ ꢀ7:0 (c 0.54, EtOH) {lit.13
27
½aꢁD ¼ ꢀ7:1 (c 0.15, EtOH)}; IR (KBr): m = 3443, 2951,
2919, 1742, 1451, 1374, 1219, 1165 cmꢀ1 1H NMR
;
(200 MHz, CDCl3): d = 2.01–2.12 (2H, m), 2.42–2.62
(2H, m), 3.65 (3H, s), 3.97–4.07 (3H, m), 4.59 (1H, d,
J = 4.5 Hz), 7.25 (1H, d, J = 7.0 Hz), 7.33 (2H, t,
J = 7.0 Hz), 7.41 (2H, d, J = 7.0 Hz); 13C NMR
(CDCl3, 75 MHz): d = 174.9, 139.8, 128.7, 127.9,
126.3, 86.1, 85.3, 80.7, 79.0, 51.9, 30.6, 23.7; HRMS
calcd for C14H18O5Na [M+Na]+ 289.1051, found
289.1059.
10. Somfai, P. Tetrahedron 1994, 50, 11315.
11. (a) Mukai, C.; Hirai, S.; Kim, I. J.; Hanaoka, M.
Tetrahedron Lett. 1996, 37, 5389; (b) Mukai, C.; Hirai,
S.; Hanaoka, M. J. Org. Chem. 1997, 62, 6619.
12. (a) Babjak, M.; Kapitan, P.; Gracza, T. Tetrahedron Lett.
2002, 43, 6983–6985; (b) Babjak, M.; Kapitan, P.; Gracza,
T. Tetrahedron 2005, 61, 2471.
Acknowledgments
A. K. Raju and G. Rajaiah thank the CSIR, New Delhi,
for a research fellowship.
13. Yoda, H.; Nakaseko, Y.; Takabe, K. Synlett 2002, 1532.
14. Yoda, H.; Shimojo, T.; Takabe, K. Synlett 1999, 1969.
15. Yadav, J. S.; Rajaiah, G.; Raju, A. K. Tetrahedron Lett.
2003, 44, 5831–5833.
16. (a) Katzuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980,
102, 5954; (b) Sharpless, K. B.; Woodward, S. S.; Finn, M.
G. Pure Appl. Chem. 1983, 55, 1823; (c) Melloni, P.
Tetrahedron 1985, 41, 1391; (d) Peter, A. J. Chem. Soc.,
Perkin Trans. 1 1990, 2775.
17. (a) Mancuso, A. J.; Swern, D. Synthesis 1981, 165; (b)
Schmitz, W. D.; Messerschmidt, N. B.; Romo, D. J. Org.
Chem. 1998, 63, 2058.
18. (a) Wittig, G.; Rieber, M. Ann. 1949, 562, 187; (b) Wittig,
G.; Geissler, G. Ann. 1953, 580, 44; (c) Wittig, G.;
Schollkopf, V. Chem. Ber. 1954, 87, 1318; (d) Gensle, W.
J. Chem. Rev. 1957, 57, 191.
References
1. Cao, S.-G.; Wu, X.-H.; Sim, K.-Y.; Tan, B. K. H.; Pereira,
J. T.; Goh, S.-H. Tetrahedron 1998, 54, 2143–2148.
2. Lode, J. W.; Nearn, R. H. Heterocycles 1977, 7, 113.
3. (a) El-Zayat, A. A. E.; Ferigni, N. R.; McCloud, T. G.;
McKenzie, A. J.; Byrn, S. T.; Cassady, J. M.; Chang, C.;
McLaughlin, J. L. Tetrahedron Lett. 1985, 26, 955; (b)
Goh, S. H.; Chung, V. C.; Sha, C. K.; Mak, T. C. W.
Phytochemistry 1990, 29, 1704.
4. (a) Argoudelis, A. D.; Zieserl, J. G. Tetrahedron Lett.
1966, 18, 1969; (b) Yasui, K.; Tamura, Y.; Nakatani, T.;
Kawada, K.; Ohtani, M. J. Org. Chem. 1955, 60, 7567; (c)
Bermejo, A.; Blazqoz, M. A.; Rao, K. S.; Cortes, D.
Phytochem. Anal. 1999, 10, 127; (d) Ahmad, F. B.; Tuko,
W. A.; Omar, S.; Sharif, A. M. Phytochemistry 1991, 30,
2430; (e) Fang, X. P.; Anderson, J. E.; Chung, C. J.;
Mclanglin, J. L.; Fanwick, P. E. J. Nat. Prod. 1991, 54,
1034.
19. Kim, N.; Choi, J.; Cha, J. K. J. Org. Chem. 1993, 58, 7096.
20. (a) Valverde, S.; Lomas, M. M.; Herradon, B.; Ochoa, S.
G. Tetrahedron 1987, 43, 1895; (b) Tronchet, J. M. J.;
Gentile, B. Helv. Chim. Acta 1979, 62, 2091.