Total synthesis of 8-methoxygoniodiol related compounds via chiron approach

Article abstract of DOI:10.1016/j.tetasy.2009.05.034

The stereoselective synthesis of 8-methoxygoniodiol related compounds was accomplished by using readily available δ-gluconolactone as a chiral source. The stereoselective addition of an aryl Grignard reagent on an aldehyde, stereoselective reduction of a keto group and regioselective opening of a chiral epoxide by ethyl propiolate are the key steps involved in this synthesis.

Full text of DOI:10.1016/j.tetasy.2009.05.034

Tetrahedron: Asymmetry 20 (2009) 1725–1730
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Tetrahedron: Asymmetry
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Total synthesis of 8-methoxygoniodiol related compounds via chiron approach
*
Jhillu Singh Yadav , Batta Madhava Rao, Kodepelly Sanjeeva Rao
Division of Organic Chemistry, 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:
The stereoselective synthesis of 8-methoxygoniodiol related compounds was accomplished by using
readily available d-gluconolactone as a chiral source. The stereoselective addition of an aryl Grignard
reagent on an aldehyde, stereoselective reduction of a keto group and regioselective opening of a chiral
epoxide by ethyl propiolate are the key steps involved in this synthesis.
Received 21 April 2009
Accepted 29 May 2009
Available online 17 August 2009
Ó 2009 Published by Elsevier Ltd.
1. Introduction
of 8-methoxygoniodiol are scarce.9 8-Methoxygoniodiol exhibits
very different cytotoxicity compared to (+)-goniodiol, depending
The genus Goniothalamus (Annonaceae) consists of 115 species,
spread over the entire tropic and subtropic regions,1 some of them
are used extensively as traditional medicines.2 Several bioactive
styryllactones have been isolated from Goniothalamus species.3,4
The seeds of G. amuyon are reported to be useful for the treatment
of edema and rheumatism.5 In particular, 8-methoxygoniodiol was
isolated from the stems and leaves of Goniothalamus amuyon along
with seven styrylpyrones.6 These styryllactones are found to pos-
sess significant cytotoxicity against several human tumors.7 The
structures of some styryllactones including their related com-
pounds are depicted in Figure 1.
on the type of human cancer cell lines. Hence we have synthesised
the analogues containing different alkyl groups. As part of our ongo-
ing program in the synthesis of heavily oxygenated lactones from
sugars, we have recently disclosed, from d-gluconolactone one of
these novel styryllactone ((+)-8-methoxygoniodiol).10 As an exten-
sion of our previous synthetic endeavor, we now describe stereose-
lective synthesis of 3–5 from d-gluconolactone as replenishable
starting material with full experimental details. Retrosynthetic
analysis of 3–5 is depicted in Scheme 1.
The retrosynthetic analysis of 3–5 illustrates that optically ac-
tive epoxides 15a, 15b, 23 could be prepared from d-gluconolac-
tone 6 by a sequence of reactions. Subsequently, epoxides 15a,
15b, 23 could be easily converted into target molecules 3–5 by
means of ring opening by ethyl propiolate followed by partial
hydrogenation using Lindlar’s catalyst.
O
O
O
OH
O
O
OH
(+)-Goniodiol 1
OH
8-Methoxygoniodiol 2
2. Results and discussion
The synthesis of styryllactones 3, 4, 5 began with d-gluconolac-
tone 6, which could be easily obtained from a commercial source.
Accordingly, d-gluconolactone 6 was treated with methanol in the
presence of p-TSA followed by 2,2-dimethoxypropane to give com-
pound 7 in 86% yield.11 Reduction of ester 7 with LiAlH4 gave diol 8
in 96% yield, which upon treatment with NaIO4 furnished aldehyde
9 in 90% yield. The addition of phenylmagnesium bromide to an
aldehyde 9 predominantly gave compound 10 along with a minor
amount of compound 10a. The diastereomeric ratio of 10 to 10a
was 95:5, which could be easily separated by column chromatog-
raphy. The configuration of the newly formed hydroxyl group
was assigned by converting the compound 10 into a known
product.12
O
O
O
O
O
( )10
( )4
O
O
O
O
OH
OH
OH
5
4
3
Figure 1.
Owing to their potent biological activity, and structural architec-
ture, several methods have been reported for the synthesis of (+)-
goniodiol and related molecules.8 However, reports on the synthesis
The hydroxyl group of major isomer 10 was protected as its alkyl
ethers 11a and 11b using n-hexyl bromide, n-dodecylbromide, and
NaH in THF in the presence of a catalytic amount of TBAI. Hydrolysis
* Corresponding author. Tel./fax: +91 40 27160512.
E-mail address: yadav@iict.res.in (J.S. Yadav).
0957-4166/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2009.05.034

1726
J. S. Yadav et al. / Tetrahedron: Asymmetry 20 (2009) 1725–1730
OH
O
OH
Ph
Ph
OR
HO
O
Ph
O
O
OR
OR
O
3-5
O
O
O
O
HO
HO
O
OH
OH
OH
O
OH
δ-Gluconolactone
Scheme 1. Retrosynthetic analysis of 3–5.
of the primary acetonide and cleavage of the resulting diol occurred
simultaneously with H5IO6 at room temperatureresultingin thecor-
responding aldehydes 12a and 12b in 95% yield.13 Reduction of alde-
hydes 12a and 12b with NaBH4 in methanol gave the corresponding
alcohols 13a and 13b in 90% yield, which were then converted into
the corresponding iodides 14a and 14b by using I2, TPP and imidaz-
ole. Upon treatment of iodides 14a and 14b with 1 M HCl in ethanol
for 3 days, followed by the addition of excess K2CO3 we obtained the
corresponding hydroxy epoxides 15a and 15b in 70% yield.14 The hy-
droxyl group of the epoxides were then protected as the correspond-
ing TBS ethers 16a and 16b using TBSCl and imidazole. Treatment of
the obtained ethers 16a and 16b with ethyl propiolate in the pres-
ence of n-BuLi and BF3.OEt2 afforded the ring opened products 17a
and 17b in 80% yield. Partial hydrogenation of these compounds
17a and 17b under Lindlar’s conditions followed by treatment with
1 M HCl gave the corresponding target molecules 3 and 4 in 60%
yield (Scheme 2).
Having successfully studied the formation of 3 and 4 using d-
gluconolactone 6, we then proceeded to apply a similar strategy
to construct the 8-methoxy goniodiol epimer 5 from the same
starting material (d-gluconolactone). The diastereomeric mixture
of alcohols 10 and 10a were then oxidized to corresponding keto
compound 18 using IBX in THF at room temperature. The keto
group of compound 18 was reduced stereoselectively to compound
19 as a major isomer (95:5) using NaBH4/CeCl3 system at ꢀ78 °C.
Compound 19 was smoothly converted to 8-methoxygoniodiol
epimer 5 using the same reaction sequence as mentioned in
Scheme 2. The structures of the newly synthesized styryllactones
O
O
HO
HO
a
b
O
O
O
O
O
O
O
c
OH
OMe
OH
OH
O
OH
OH
O
6
7
8
O
O
O
O
O
O
e (ii) for 11a
e (iii) for 11b
O
O
O
O
O
O
d
+
Ph
OR
H
O
Ph
Ph
OH
O
O
OH
O
O
O
9
10
10a
11a: R = n-hexyl
11b: R = n-dodecyl
O
O
O
g
f
Ph
OR
i
Ph
OR
h
Ph
OR
I
HO
H
O
O
O
14a: R = n-hexyl
14b: R = n-dodecyl
13a: R = n-hexyl
13b: R = n-dodecyl
12a: R = n-hexyl
12b: R = n-dodecyl
OTBS
Ph
OH
OH
OTBS
O
Ph
Ph
j
O
k
l
Ph
EtO
OH OR
O
OR
OR
OR
O
O
17a: R = n-hexyl
15a: R = n-hexyl
16a: R = n-hexyl
17b: R = n-dodecyl
15b: R = n-dodecyl
16b: R = n-dodecyl
3: R = n-hexyl
4: R = n-dodecyl
Scheme 2. Reagents and conditions: (a) 2,2-DMP, p-TSA, acetone, MeOH, 12 h, rt, 86%; (b) LiAlH4, THF, 0 °C–rt, 4 h, 96%; (c) NaIO4, DCM, aq satd NaHCO3, 5 h, 90%; (d)
PhMgBr, THF, ꢀ5 °C–0 °C–rt (a:b: 95:5) 1/2 h, 95%; (e) (i) NaH, n-hexyl bromide, TBAI, THF, 0 °C–rt, 2 h, 97%; (ii) NaH, n-dodecyl bromide, TBAITHF, 0 °C–rt, 2 h, 97%; (f) H5IO6,
EtOAc, 0 °C–rt, 1 h, 95%; (g) NaBH , MeOH, 0 °C–rt, 2 hC, 9O0%;E(th,) TPP, I , imidazole, CH CN:ether (1:3) 0 °C–rt, 2 h, 90%; (i) 1 M HCl, EtOH, 0 °C–rt, 3 days then K CO , 70%; (j)
4
2
2
3
imidazole, TBSCl, CH2Cl2, 0 °C–rt, 2 h, 90%; (k)
, BuLi, BF3OEt2, THF, ꢀ378 °C, 2 h, 80%; (l) (i) Lindlar, EtOAc; (ii) 1 M, HCl, 60%.
2

J. S. Yadav et al. / Tetrahedron: Asymmetry 20 (2009) 1725–1730
1727
O
O
O
O
O
O
O
O
O
a
b
Ph
OH
c
Ph
Ph
OH
O
O
O
O
19
10+10a
18
O
O
O
O
O
e
f
Ph
Ph
d
g
HO
I
Ph
O
O
O
O
O
O
21
22
20
OTBS
OH
Ph
Ph
OH
h
O
O
Ph
O
O
OH
24
O
O
O
O
5
23
Scheme 3. Reagents and conditions: (a) IBX, DMSO, THF, rt, 2 h, 91%; (b) NaBH4, CeCl3, MeOH, ꢀ78 °C, 2 h, 86%; (c) NaH, MeI, THF, 0 °C–rt, 2 h, 96%; (d) (i) H5IO6, EtOAc, 0 °C–
rt, 1 h, 95%; (ii) NaBH4, MeOH, 0 °C–rt, 2 h, 90%; (e) TPP, I2, imidazole, CH3CN:ether (1:3) 0 °C–rt, 2 h, 90%; (f) 1 M HCl, EtOH, 0 °C–rt, 3 days then K2CO3, 70%; (g) (i) imidazole,
CO Et,
TBSCl, CH2Cl2, 0 °C–rt, 2 h, 90%; (ii)
, BuLi, BF3OEt2, THF, ꢀ78 °C, 2 h, 80%; (h) (i) Lindlar, EtOAc; (ii) 1 M HCl, 60%.
2
3, 4, 5 were fully characterized using 1H NMR, 13C NMR, IR, HRMS
including rotation values (Scheme 3).
1.32 (4s, 12H). 13C NMR (50 MHz, CDCl3): d 172.9, 110.0, 109.8,
80.8, 77.2, 76.4, 69.4, 67.8, 52.6, 27.1, 26.6, 26.5, 25.2. IR (KBr): mmax
3475, 2986, 2925, 1741, 1456, 1375, 1244, 1152, 1070, 845 cmꢀ1
,
½
a 2D5
ꢁ
¼ þ10:2 (c 1.0, CHCl3).
3. Conclusions
4.1.2. (S)-1-((4R,40R,5R)-2,2,20,20-Tetramethyl-4,40-bi(1,3-dioxo-
lan)-5-yl)ethane-1,2-diol 8
In conclusion, we have described a concise and highly stereose-
lective synthetic route for the synthesis of 8-methoxygoniodiol re-
lated compounds using the readily available d-gluconolactone as a
chiral precursor. The synthesis involves direct and straightforward
reactions such as the aryl Grignard addition, the stereoselective
reduction of the keto group, the epoxide formation from an
iodohydrin and the stereoselective ring opening of epoxide by an
alkyne, which makes it quite simple and more convenient for
scale-up products.
To a suspension of LiAlH4 (4.70 g, 231 mmol) in anhydrous THF
(200 mL) at 0 °C, was added hydroxy-ester 7 (25 g, 154 mmol) in
THF (65 mL). The mixture was stirred for 4 h at room temperature
and quenched with aqueous Na2SO4 solution at 0 °C. The clear
solution was filtered and the residue was washed with ethyl ace-
tate (100 mL). The combined organic layers were washed with
brine solution, dried over Na2SO4 and concentrated in vacuo. The
resulting residue was purified by column chromatography to give
pure diol 8 (21.1 g, 96%) as a white crystalline solid. 1H NMR
(300 MHz, CDCl3): d 4.17–3.90 (m, 5H), 3.74–3.70 (m, 3H), 2.62
and 2.44 (2s, 2H), 1.41, 1.39, 1.36 and 1.32 (4s, 12H). 13C NMR
(75 MHz, CDCl3): d 135.6, 117.4, 96.2, 56.9, 51.3, 48.7, 38.9, 32.5,
23.9, 23.1. IR (KBr): mmax 3446, 2987, 2925, 1638, 1457, 1376,
1248, 1214, 1156, 1068, 846 cmꢀ1, LC–MS: m/z 285 (M+Na)+,
4. Experimental
4.1. General
Melting points were recorded on Buchi R-535 apparatus and are
uncorrected. IR spectra were recorded on a Perkin–Elmer FT-IR
240-c spectrophotometer using KBr optics. 1H NMR and 13C spectra
were recorded on Gemini-200 and Varian Bruker-300 spectrome-
ter in CDCl3 using TMS as internal standard. Mass spectra were re-
corded on a Finnigan MAT 1020 mass spectrometer operating at
70 eV. The optical rotations were measured on a Jasco Dip 360 Dig-
ital polarimeter.
½
a 2D5
ꢁ
¼ þ7:24 (c 1.75, CHCl3).
4.1.3. (R)-Phenyl((4R,40R,5R)-2,2,20,20-tetramethyl-4,40-bi(1,3-
dioxolan)-5-yl)methanol 10
A solution of diol 8 (25 g, 430 mmol) in DCM (500 mL) contain-
ing aqueous saturated NaHCO3 (35 mL) was treated with NaIO4
(41 g, 860 mmol) portionwise at 0 °C and stirred at below 20 °C
for 5 h. Solid Na2SO4 (50 g) was added, and the mixture was stirred
for an additional 15 min, filtered, washed with DCM (250 mL) and
the solvent evaporated to afford aldehyde 9 (19.5 g, 90%) as a yel-
lowish oil, which was immediately used for the next reaction with-
out additional purification.
To a solution of Grignard reagent [prepared in situ from Mg
(2.82 g, 300 mmol) and phenylbromide (18.4 g, 300 mmol) in THF
(450 mL)] at ꢀ5 °C was added a solution of the crude aldehyde 9
(18.0 g, 200 mmol) in THF (150 mL). The mixture was allowed to
reach from 0 °C to room temperature slowly and after 30 min,
quenched with aqueous saturated NH4Cl. Workup with Et2O
(3 ꢂ 200 mL), brine wash, dried (Na2SO4) and removal of the sol-
vent followed by purification gave enantiomerically pure alcohol
4.1.1. (R)-Methyl 2-hydroxy-2-((4R,40R,5R)-2,2,20,20-tetramethyl-
4,4-bis(1,3-dioxolan)-5-yl) acetate 7
D
-Glucono-1,5-lactone 6 (89 g, 400 mmol) in 2,2-dimethoxy
propane (150 mL), dry acetone (50 mL) and absolute methanol
(15 mL) were added to p-TSA (1.0 g, 4.2 mmol). After stirring for
12 h, the homogenous solution was neutralized with NaHCO3 and
filtered, evaporated and the resulting residue in DCM (400 mL)
was washed with brine solution, and dried over Na2SO4. Concen-
tration of the solvent followed by silica gel column chromatogra-
phy gave the
a-hydroxy-ester 7 (123 g, 86%) as a yellowish oil.
1H NMR (300 MHz, CDCl3): d 4.25 (d, J = 7.17 Hz, 1H), 4.15–3.94
(m, 5H), 3.84 (s, 3H), 2.89 (d, J = 8.30 Hz, 1H), 1.41, 1.37, 1.34 and

1728
J. S. Yadav et al. / Tetrahedron: Asymmetry 20 (2009) 1725–1730
10 (21.75 g, 95%) as a white solid. 1H NMR (CDCl3, 300 MHz): d
1.41, 1.37, 1.34, 1.32 (4s, 12H), 3.90–4.20 (m, 5H), 4.25 (d,
J = 4.6 Hz, 1H), 7.3 (m, 5H). 13C NMR (CDCl3, 75 MHz): d 25.1,
26.3, 26.6, 27.1, 72.6, 75.4, 76.7, 82.6, 83.6, 109.0, 110.0, 126.8,
127.7, 128.5, 140.0. IR (KBr): mmax 3438, 2990, 2874, 1376, 1153,
4.1.7. ((4R,5R)-5-((R)-Dodecyloxy(phenyl)methyl)-2,2-dimethyl-
1,3-dioxolan-4-yl)methanol 13b
Compound 13b was prepared starting from 11b (86% overall
yield for two steps, colorless oil) in the same way as 13a. 1H
NMR (CDCl3, 200 MHz): d 0.88 (t, J = 6.61 Hz, 3H), 1.12 (s, 3H),
1.19–1.33 (m, 18H), 1.35 (s, 3H), 1.52–1.61 (m, 2H), 3.09–3.47
(m, 4H), 3.69–3.78 (m, 1H), 4.01 (dd, J = 5.87, 8.08 Hz, 1H), 4.42
(d, J = 5.87 Hz, 1H), 7.25–7.32 (m, 5H), 13C NMR (CDCl3, 75 MHz):
d 13.9, 24.3, 25.5, 25.9, 26.6, 27.1, 29.3, 29.3, 29.6, 31.8, 62,5,
69.5, 77.50, 80.1, 82.4, 109.1, 127.2, 127.8, 128.2, 137.3, IR (KBr):
1070, 843, 702 cmꢀ1
.
HRMS calcd for C17H24O5 [M+Na]+
331.1521. Found: 331.1512.
4.1.4. (4R,40R,5R)-5-((R)-Hexyloxy(phenyl)methyl)-2,2,20,20-
tetramethyl-4,40-bi(1,3-dioxolane) 11a
To a stirred suspension of NaH (1.29 g, 150 mmol, 60% w/v dis-
persion in mineral oil) in anhydrous THF (60 mL), a solution of
alcohol 10 (6 g, 100 mmol) in dry THF (25 mL) was added dropwise
at 0 °C. After 30 min, n-hexyl bromide (9.58 g, 300 mmol) and tet-
rabutylammonium iodide (0.35 g, 5 mmol) was added. Stirring was
continued for 2 h at room temperature, the reaction mixture was
quenched with ice pieces. The aqueous layer was extracted with
EtOAc (3 ꢂ 5 mL). The organic phase was washed with brine, dried
(Na2SO4) and concentrated followed by column chromatography to
afford the compound 11a (7.40 g, 97%) as a white solid. 1H NMR
(CDCl3, 200 MHz): d 0.87 (t, J = 6.25 Hz, 3H), 1.17–1.61(m, 20H),
3.21–3.39 (m, 2H), 3.79–4.09 (m, 5H), 4.25 (d, J = 3.12 Hz, 1H),
7.18–7.39 (m, 5H). 13C NMR (CDCl3, 75 MHz): d 13.9, 22.5, 25.2,
25.8, 26.4, 26.9, 27.6, 29.7, 31.5, 66.5, 69.2, 78.8, 81.6, 82.5, 83.0,
109.2, 109.9, 127.8, 128.1, 139.0 IR (KBr): mmax 3451, 2929, 2861,
m
max: 3404, 2924, 2853, 1458, 756, 698 cmꢀ1. HRMS calcd for
C25H42O4 [M+Na]+ 429.2980. Found: 429.2977, ½a 2D5
¼ þ31:5 (c
ꢁ
1.40, CHCl3).
4.1.8. (4R,5S)-4-((R)-Hexyloxy(phenyl)methyl)-5-(iodomethyl)-
2,2-dimethyl-1,3-dioxolane 14a
A mixture of 13a (3.0 g, 50 mmol), triphenyl phosphine (4.8 g,
100 mmol), imidazole (1.57 g, 125 mmol) and iodine (4.71 g,
100 mmol) in DCM (180 mL) was stirred at room temperature for
5 h then cooled to 0 °C, after which excess of iodine was removed
by the addition and washing with aqueous Na2S2O3 (45 mL). The
reaction mixture was extracted with DCM (3 ꢂ 15 mL), washed
with brine, dried over Na2SO4 and concentrated. Purification by
column chromatography yielded compound 14a (3.61 g, 90%) as
a colorless oil. 1H NMR (CDCl3, 200 MHz): d 0.94 (t, J = 5.90 Hz,
3H), 1.29–1.43 (m, 9H), 1.50 (s, 3H), 1.60–1.68 (m, 2H), 2.67 (dd,
J = 5.16, 10.33 Hz, 1H), 2.96 (dd, J = 3.68, 10.33 Hz, 1H), 3.42 (t,
J = 5.09 Hz, 3H), 3.55–3.64 (m, 1H), 3.94–4.03 (m, 1H), 4.41 (d,
J = 5.90 Hz, 1H), 7.33–7.41 (m, 5H), 13C NMR (CDCl3, 75 MHz): d
7.3, 14.0, 22.5, 25.7, 27.1, 27.5, 29.6, 31.5, 69.2, 76.1, 82.7, 83.5,
109.6, 127.6, 128.4, 128.5, 137.7, IR (KBr): mmax 3858, 3755, 3448,
1455, 1374, 1069, 761, 703 cmꢀ1
. HRMS calcd for C23H36O5
[M+Na]+ 415.2460. Found: 415.2442. ½a 2D5
¼ þ29:3 (c 7.85, CHCl3).
ꢁ
4.1.5. (4R,40R,5R)-5-((R)-Dodecyloxy(phenyl)methyl)-2,2,20,20-
tetramethyl-4,40-bi(1,3-dioxolane) 11b
Compound 11b was prepared (97%, white solid) in the same
way as compound 11a. 1H NMR (CDCl3, 200 MHz): d 0.88 (t,
J = 6.58 Hz, 3H), 1.19–1.54 (m, 32H), 3.19–3.39 (m, 2H), 3.82–
4.11 (m, 5H), 4.32 (d, J = 3.65, 1H), 7.27–7.34 (m, 5H). 13C NMR
(CDCl3, 75 MHz): d 13.8, 22.4, 25.0, 29.9, 26.1, 26.8, 26.9, 27.3,
27.4, 29.0, 29.1, 29.3, 29.4, 31.6, 69.3, 76.7, 78.7, 81.7, 82.2, 82.9,
109.3, 110.0, 127.8, 128.2, 128.3, 138.9. IR (KBr): mmax 3457,
2926, 2854, 1452, 1374, 1068, 761, 700 cmꢀ1 HRMS calcd for
2926, 2858, 1740, 760 cmꢀ1. LC–MS: [M+Na]+ 455, ½a 2D5
¼ þ53:2
ꢁ
(c 1.75, CHCl3).
4.1.9. (4R,5S)-4-((R)-Dodecyloxy(phenyl)methyl)-5-(iodomethyl)-
2,2-dimethyl-1,3-dioxolane 14b
Compound 14b was prepared starting from 13b (90%, colorless
oil) in the same way as 14a. 1H NMR (CDCl3, 300 MHz): d 0.91 (t,
J = 6.79 Hz, 3H), 1.25–1.46 (m, 24H), 1.53–1.66 (m, 2H), 2.62 (dd,
J = 5.28, 10.57 Hz, 1H), 2.92 (dd, J = 3.77, 10.57 Hz, 1H), 3.33–3.43
(m, 2H), 3.52–3.58(m, 1H), 3.94 (t, J = 6.79 Hz, 1H), 4.38 (d,
J = 6.04 Hz, 1H), 7.28–7.40 (m, 5H), 13C NMR (CDCl3, 75 MHz): d
7.3, 14.0, 22.6, 26.1, 27.5, 29.5, 31.9, 69.2, 76.1, 82.6, 83.5, 109.6,
127.1, 127.6, 128.4, 137.7, IR (KBr): mmax 3449, 2924, 2856, 2365,
C29H48O5 [M+Na]+ 499.3399 Found: 499.3416. ½a 2D5
¼ þ26:5 (c
ꢁ
4.1, CHCl3).
4.1.6. ((4R,5R)-5-((R)-Hexyloxy(phenyl)methyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)methanol 13a
A solution of compound 11a (6 g, 100 mmol) in EtOAc (100 mL)
containing H5IO6 (6.97 g, 200 mmol) was stirred for 2 h at rt and
then quenched with solid NaHCO3. The resulting mixture was fil-
tered and concentrated to give aldehyde 12a (4.65 g, 95%) which
was used as such for the next reaction immediately without
purification.
To a stirred solution of above aldehyde 12a (4.65 g, 50 mmol) in
dry MeOH (50 mL), NaBH4 (1.04 g, 100 mmol) was added at 0 °C
and stirred at room temperature for 2 h. Methanol was evaporated
and the residue was dissolved in aqueous NH4Cl (50 mL) and then
extracted with EtOAc (3 ꢂ 15 mL). The organic phase was washed
with brine solution, dried over Na2SO4, concentrated in vacuo
and the resulting residue was purified by column chromatography
to afford alcohol 13a (4.21 g, 90% or 86% overall yield for two steps)
as a colorless oil. 1H NMR (CDCl3, 200 MHz): d 0.90 (t, J = 6.79 Hz,
3H), 1.39 (s, 3H), 1.29–1.40 (m, 9H), 1.54–1.66 (m, 2H), 3.13–
3.42 (m, 5H), 3.75 (m, 1H), 4.02 (dd, J = 6.04 and 8.30 Hz, 1H),
4.42 (d, J = 6.04 Hz, 1H), 7.25–7.36 (m, 5H). 13C NMR (CDCl3,
75 MHz): d 13.9, 22.5, 25.6, 26.6, 27.2, 29.5, 31.5, 62.6, 69.4, 77.5,
1457, 760, 703 cmꢀ1
.
HRMS calcd for C25H41O3I [M+Na]+
539.1998. Found: 539.2018, ½a D25
¼ þ33:3 (c 0.90, CHCl3).
ꢁ
4.1.10. (1R,2R)-2-(Hexyloxy)-1-((R)-oxiran-2-yl)-2-phenylethanol
15a
Iodo derivative 14a (2.5 g, 40 mmol) in ethanol (25 mL) was
treated with 1 M HCl (10 mL) at 0 °C and stirred at room tempera-
ture for 3 days. After completion of the reaction by TLC, the reac-
tion mixture was basified (pH 10) with solid K2CO3 then stirred
for 12 h. The reaction mixture was filtered and washed with chlo-
roform (3 ꢂ 30 mL). The combined organic layers dried over anhy-
drous Na2SO4 and concentrated. The crude residue was purified by
column chromatography on silica gel to furnish pure diol 15a
(1.06 g, 70%) as a colorless oil. 1H NMR (CDCl3, 200 MHz): d 0.88
(t, J = 6.61 Hz, 3H), 1.24–1.56 (m, 8H), 2.50–2.54 (m, 2H), 2.70–
2.72 (m, 1H), 3.28–3.40 (m, 3H), 3.63–3.67 (m, 1H), 4.25 (d,
J = 8.08 Hz, 1H), 7.25–7.36 (m, 5H), 13C NMR (CDCl3, 75 MHz): d
13.9, 22.5, 25.7, 29.6, 31.5, 44.1, 51.5, 69.2, 74.2, 83.5, 127.4,
128.3, 128.5, 138.2, IR (KBr): mmax 3457, 2927, 2862, 1713, 1457,
80.1, 82.4, 109.2, 127.8, 128.1, 128.2, 137.3, IR (KBr):
m
max: 3449,
2925, 2856, 1636, 1215, 760, 704, 669 cmꢀ1
. HRMS calcd
for C19H30O4 [M+Na]+ 345.2041. Found: 345.2054. ½a 2D5
ꢁ
¼ þ43:9
1097, 759, 703 cmꢀ1
,
HRMS calcd for C16H24O3 [M+Na]+
287.1623. Found: 287.1635, ½a D25
¼ þ28:0 (c 0.25, CHCl3).
ꢁ
(c 1.65, CHCl3).

J. S. Yadav et al. / Tetrahedron: Asymmetry 20 (2009) 1725–1730
1729
4.1.11. (1R,2R)-2-(Dodecyloxy)-1-((R)-oxiran-2-yl)-2-phenyl-
ethanol 15b
column chromatography to afford pure saturated compound 3
(0.190 g, 60%) as a colorless oil. 1H NMR (CDCl3, 200 MHz): d 0.87
(t, J = 6.25 Hz, 3H), 1.16–1.41 (m, 6H), 1.48–1.68 (m, 2H), 2.09
(ddd, J = 3.90, 6.25, 18.75 Hz, 1H), 2.82–3.04 (m, 1H), 3.26 (br m,
–OH, 1H), 3.36 (t, J = 7.03 Hz, 2H), 3.64 (d, J = 8.59 Hz, 1H), 3.99
(dd, J = 2.34, 12.50 Hz, 1H), 4.64 (d, J = 8.59 Hz, 1H), 5.95 (dd,
J = 1.56, 9.37 Hz, 1H), 6.82 (ddd, J = 3.90, 7.03, 14.84 Hz, 1H),
7.30–7.55 (m, 5H), 13C NMR (CDCl3, 75 MHz): d 13.9, 22.5, 25.7,
25.8, 29.6, 31.5, 69.2, 75.5, 75.9, 81.6, 120.7, 127.6, 128.4 (2C),
128.6, 137.9, 145.6, 163.8, IR (KBr): mmax 3455, 2926, 2856, 1731,
1250, 1095, 703, 633 cmꢀ1, HRMS calcd for C12H26O4 [M+Na]+
Compound 15b was prepared starting from 14b (70%, colorless
oil) in the same way as 15a. 1H NMR (CDCl3, 300 MHz): d 0.89 (t,
J = 6.60 Hz, 3H), 1.09–1.43 (m, 18H), 1.49–1.62 (m, 2H), 2.49–
2.57 (m, 2H), 2.69–2.72 (m, 2H), 3.28–3.41 (m, 2H), 3.61–3.68
(m, 1H), 4.25 (d, J = 8.80 Hz, 1H), 7.28–7.37 (m, 5H), 13C NMR
(CDCl3, 75 MHz): d 14.0, 22.6, 26.1, 29.3, 29.4, 29.5, 29.7, 31.8,
44.5, 51.8, 69.6, 73.8, 77.2, 83.6, 127.2, 128.06, 128.4, 138.7, IR
(KBr): mmax 3401, 2927, 2858, 2370, 1716, 1393, 757, 699 cmꢀ1
,
LC–MS: [M+Na]+ 371, ½a D25
¼ ꢀ34 (c 1.0, CHCl3).
ꢁ
341.1728. Found: 341.1739, ½a D25
¼ ꢀ0:8 (c 0.50, CHCl3).
ꢁ
4.1.12. (5R,6S,7R)-Ethyl 6-(tert-butyldimethylsilyloxy)-7-(hexyl-
oxy)-5-hydroxy-7-phenylhept-2-ynoate 17a
4.1.15. (R)-6-((1S,2R)-2-(Dodecyloxy)-1-hydroxy-2-phenyl-
ethyl)-5,6-dihydro-2H-pyran-2-one 4
To a solution of epoxy alcohol 15a (1.0 g, 25 mmol), and imidaz-
ole (0.77 g, 75 mmol) in dry DCM (30 mL) at room temperature
was added TBDMSCl (0.82 g, 37.5 mmol) in small portions and then
DMAP (23 mg, 1.25 mmol). The mixture was stirred for 5 h, poured
Compound 4 was prepared starting from 17b (60%, colorless oil)
in the same way as 4. 1H NMR (CDCl3, 300 MHz): d 0.88 (t,
J = 6.79 Hz, 3H), 1.21–1.33 (m, 18H), 1.51–1.60 (m, 2H), 2.09
(ddd, J = 3.37, 5.28, 18.12 Hz, 1H), 2.87–3.30 (m, 1H), 3.34 (t,
J = 6.79 Hz, 2H), 3.62 (d, J = 9.06 Hz, 1H), 3.99 (dd, J = 2.26,
12.08 Hz, 1H), 4.65 (d, J = 8.30 Hz, 1H), 5.96 (dd, J = 1.51, 9.82 Hz,
1H), 6.86 (ddd, J = 1.15, 6.79, 14.35 Hz, 1H), 7.30–7.43 (m, 5H),
13C NMR (CDCl3, 75 MHz): d 14.0, 22.6, 25.8, 26.1, 29.3, 29.6,
31.9, 69.2, 75.5, 75.9, 81.6, 120.8, 127.7, 128.4, 128.6, 138.0,
145.6, 163.8, IR (KBr): mmax 3450, 2925, 2854, 1734, 816, 760,
701 cmꢀ1, HRMS calcd for C25H38O4 [M+Na]+ 425.2667. Found:
into
a dilute solution of NaHCO3 and extracted with DCM
(3 ꢂ 10 mL). The organic phase was washed with brine, dried
(Na2SO4) and concentrated followed by column chromatography
to give protected epoxide 16a (1.28 g, 90%) as a colorless oil.
To a stirred solution of the ethyl propiolate 16a (0.26 gm,
24 mmol) in dry THF (20 mL), n-BuLi (0.20 g, 24 mmol) and
BF3.OEt2 (0.44 g, 24 mmol) was added at ꢀ78 °C and stirred for
30 min at the same temperature. Next the protected epoxide
(1.0 g, 20 mmol) in dry THF was added to the reaction mixture
and stirred for 2 h at ꢀ78 °C. The reaction mixture was quenched
with aqueous NH4Cl solution (30 mL) and extracted with EtOAc
(3 ꢂ 25 mL). The organic layer was washed with brine, dried
(Na2SO4), evaporated and the residue obtained was purified by col-
umn chromatography to afford alcohol 17a (1.0 g, 80% or 71% over-
all yield for two steps) as a colorless oil. 1H NMR (CDCl3, 200 MHz):
d 0.18 (s, 3H), 0.20 (s, 3H), 0.90 (t, J = 6.61 Hz, 3H), 0.94 (s, 9H),
1.20–1.38 (m, 11H), 2.37–2.41 (m, 2H), 3.17–3.28 (m, 2H), 3.89
(d, J = 8.08 Hz, 1H), 4.04–4.25 (m, 5H), 7.28–7.34 (m, 5H), 13C
NMR (CDCl3, 75 MHz): d ꢀ3.8, ꢀ4.8, 13.9, 18.5, 25.1, 25.7, 26.1,
29.6, 31.5, 68.8, 68.8, 74.7, 76.7, 84.0, 85.4, 127.8, 128.1, 128.5,
138.9, 153.4, IR (KBr): mmax 3529, 2929, 2857, 2235, 1714, 1252,
425.2655, ½a 2D5
¼ ꢀ3:50 (c 1.0, CHCl3).
ꢁ
4.1.16. Phenyl((4R,40R,5S)-2,2,20,20-tetramethyl-4,40-bi(1,3-dioxo-
lan)-5-yl)-methanone 18
To a stirred solution of IBX (5.11 g, 200 mmol) in DMSO (15 ml)
at 25 °C was added dropwise a solution of 10 and 10a (6.0 g,
180 mmol) in THF (60 ml). The resulting mixture was stirred at
25 °C for 2 h. Solid was filtered and washed with ether. The filtrate
was extracted with ether, washed with water, brine and dried over
Na2SO4. Concentrated under reduced pressure and purification by
silica gel chromatography afforded compound 18 (5.42 g, 91%) as
a white solid. 1H NMR (CDCl3, 300 MHz): d 1.29, 1.32, 1.37, 1.48
(4s, 12H), 3.97 (dd, J = 4.53 and 8.30, 1H), 4.10–4.21 (m, 2H),
4.63–4.68 (m, 1H), 5.12 (d, J = 4.53 Hz, 1H), 7.48 (t, J = 7.55 Hz,
2H), 7.55–7.60 (m, 1H), 8.10(d, J = 6.79 Hz, 1H) 13C NMR (CDCl3,
75 MHz): d 24.7, 25.9, 26.0, 27.0, 66.6, 76.1, 77.4, 79.4, 79.4,
127.9, 128.9, 132.9, 196.0 IR (KBr): mmax 2990, 2874, 1720, 1376,
1153, 1070, 843, 702 cmꢀ1. HRMS calcd for C17H22O5 [M+Na]+
1069, 758, 702 cmꢀ1
,
HRMS calcd for C27H44O5Si [M+Na]+
499.2855. Found: 499.2850, ½a D25
¼ þ71:0 (c 1.0, CHCl3).
ꢁ
4.1.13. (5R,6S,7R)-Ethyl 6-(tert-butyldimethylsilyloxy)-7-(dode-
cyloxy)-5-hydroxy-7-phenylhept-2-ynoate 17b
Compound 17b was prepared starting from 15b same as 16a
followed by 17a (71% overall yield for two steps, colorless oil).
1H NMR (CDCl3, 300 MHz): d 0.16 (s, 3H), 0.20 (s, 3H), 0.88 (t,
J = 6.79 Hz, 3H), 0.93 (s, 9H), 1.24–1.30 (m, 20H), 1.32 (t,
J = 6.79 Hz, 3H), 2.35–2.41 (m, 2H), 3.10–3.30 (m, 3H), 3.87 (d,
J = 7.54 Hz, 1H), 4.08–4.26 (m, 3H), 7.25–7.35 (m, 5H), 13C NMR
(CDCl3, 75 MHz): d ꢀ3.8, ꢀ4.8, 13.9, 14.0, 18.5, 22.6, 25.1, 26.0,
26.3, 29.5, 29.6, 31.9, 61.7, 68.7, 68.8, 74.6, 77.4, 84.0, 85.4,
127.8, 128.1 (2C), 128.5, 138.9, 153.4, IR (KBr): mmax 3401, 2927,
2858, 2235, 1713, 1636, 1391, 1252, 1072, 758, 701 cmꢀ1. HRMS
calcd for C33H56O5Si [M+Na]+ 583.3794. Found: 583.3792,
329.1521. Found: 329.1512, ½a D25
¼ þ11:6 (c 0.8, CHCl3).
ꢁ
4.1.17. (S)-Phenyl((4R,40R,5R)-2,2,20,20-tetramethyl-4,40-bi(1,3-
dioxolan)-5-yl)methanol 19
To a stirred solution of compound 18 (4.5 g, 100 mmol) in dry
MeOH (45 L) was added CeCl3ꢃ7H2O (6.3 g, 120 mmol) and the
solution was stirred for 15 min. Next NaBH4 was then added por-
tion wise over a period of 1 h and stirred at the same temperature
for 1.5 h. The reaction mixture was cautiously quenched with
water (60 mL) and extracted with EtOAc (3 ꢂ 50 mL). The organic
phase was washed with brine solution, dried over Na2SO4, evap-
orated and the residue obtained was purified by column chroma-
tography afforded the required alcohol 19 (3.67 g, 86%)
predominantly (dr 95:5) as a colorless oil. 1H NMR (CDCl3,
300 MHz): d 1.34, 1.37, 1.40, 1.47 (4s, 12H), 3.84–4.23 (m, 5H),
4.70 (d, J = 6.79 Hz, 1H), 7.27–7.43 (m, 5H). 13C NMR (CDCl3,
75 MHz): d 25.1, 26.2, 27.1, 27.3, 67.2, 72.7, 76.6, 77.6, 83.2,
109.6, 109.9, 126.6, 127.7, 128.1, 140.6. IR (KBr): mmax 3438,
2990, 2874, 1376, 1153, 1070, 843, 702 cmꢀ1. HRMS calcd for
½
a 2D5
ꢁ
¼ þ54:10 (c 1.0, CHCl3).
4.1.14. (R)-6-((1S,2R)-2-(Hexyloxy)-1-hydroxy-2-phenylethyl)-
5,6-dihydro-2H-pyran-2-one 3
A mixture of 17a (0.50 g, 6.4 mmol) in EtOAc (10 mL) containing
10% Lindlar catalyst (30 mg) was stirred under a hydrogen atmo-
sphere for 1 h at room temperature. Aqueous 1 M HCl (0.5 ml)
solution was added to the reaction mixture and stirring continued
for 2 h at room temperature. The reaction mixture was quenched
with NaHCO3, filtered through Celite pad, washed with EtOAc
(15 mL) and concentrated. The residue was purified by silica gel
C17H24O5 [M+Na]+ 331.1521. Found: 331.1512, ½a 2D5
¼ þ15:7 (c
ꢁ
1.0, CHCl3).

1730
J. S. Yadav et al. / Tetrahedron: Asymmetry 20 (2009) 1725–1730
4.1.18. (4R,40R,5R)-5-((S)-Methoxy(phenyl)methyl)-2,2,20,20-
tetramethyl-4,40-bi(1,3-dioxolane) 20
C
11H14O3 [M+Na]+ 217.0840. Found: 217.0843, ½a 2D5
¼ þ36:9 (c
ꢁ
2.9, CHCl3).
To a well stirred suspension of NaH (1.40 g, 300 mmol, 60% w/v
dispersion in mineral oil) in anhydrous THF (100 mL), a solution of
alcohol 19 (5.0 g, 150 mmol) in dry THF (20 mL) was added drop-
wise at 0 °C. After 30 min, methyliodide (4.6 g, 300 mmol) was
added dropwise at same temperature. The resulting mixture was
further stirred for 2 h at room temperature. After completion of
the reaction, a few ice pieces and water were added. The aqueous
layer was extracted with EtOAc (3 ꢂ 50 mL) and the organic phase
was washed with brine, dried (Na2SO4), concentrated and the res-
idue was purified on column chromatography to afford the com-
4.1.22. (5R,6S,7S)-Ethyl-6-(tert-butyldimethylsilyloxy)-5-hydroxy-
7-methoxy-7-phenylhept-2-ynoate 24
Compound 24 was prepared starting from 23 (71% overall yield
for two steps, colorless oil) in the same way as 17a. 1H NMR (CDCl3,
300 MHz) : d 0.16 (s, 3H), 0.18 (s, 3H), 0.94 (s, 9 H), 1.29 (t,
J = 7.0 Hz, 3H), 2.40 (dd, J = 3.2, 6.4 Hz, 2H), 3.13 (s, 3H), 3.23 (m,
1H), 3.86 (d, J = 7.6 Hz, 1H), 4.11 (d, J = 7.8 Hz, 1H), 4.18 (q,
J = 7.0 Hz, 2H), 7.26–7.45 (m, 5H). 13C NMR (CDCl3, 75 MHz): d -
4.9, -3.7, 14.0, 25.1, 26.2, 29.7, 56.3, 61.8, 68.7, 76.6, 85.3, 85.8,
127.8, 128.3, 128.6, 138.1, 150.4. IR (KBr): mmax 3423, 3300, 2927,
1742, 1458, 1105, 760 cmꢀ1. MASS (LC–MS): m/z 429 [M+Na]+,
pound 20 (5.0 g, 96%) as
a
colorless oil. 1H NMR (CDCl3,
300 MHz): d 1.41, 1.37, 1.34, 1.32 (4s, 12H), 3.26 (s, 3H), 3.71–
4.03 (m, 5H), 4.22 (d, J = 3.67 Hz, 1H), 7.38–7.30 (m, 5H). 13C
NMR (CDCl3, 75 MHz): d 25.1, 26.3, 26.5, 27.2, 56.4, 72.3, 75.4,
76.6, 82.5, 83.4, 109.0, 110.0, 126.0, 127.7, 128.5, 138.5. IR (KBr):
mmax 2987, 1456, 1372, 1214, 1076, 848, 706 cmꢀ1. HRMS calcd
½
a 2D5
ꢁ
¼ þ60:5 (c 1.4, CHCl3).
4.1.23. (R)-6-((1S,2S)-1-Hydroxy-2-methoxy-2-phenylethyl)-5,6-
dihydro-2H-pyran-2-one 5
for C18H26O5 [M+Na]+ 345.1676. Found: 345.1669. ½a 2D5
ꢁ
¼ þ59:6
Compound 5 was prepared starting from 24 (60%, colorless oil) in
the same way as 4. 1H NMR (CDCl3, 300 MHz): d 2.07 (ddd, J = 4.1,
6.35, 18.5 Hz, 1H), 2.94 (ddd, J = 2.4, 13.0, 18.5 Hz, 1H), 3.26 (s,
3H), 3.54 (d, J = 8.2 Hz, 1H), 3.94 (ddd, J = 3.7, 12.5, 17.5 Hz, 1H),
4.52 (d, J = 8.4 Hz, 1H), 5.93 (dd, J = 3.2, 10.4 Hz, 1H), 6.84 (ddd,
J = 2.4, 6.2, 9.4 Hz, 1H), 7.30–7.39 (m, 5H). 13C NMR (CDCl3,
75 MHz): d 25.4, 56.5, 61.7, 75.5, 75.7, 83.4, 120.7, 127.7, 128.6,
128.7, 137.3, 145.7, 163.8. IR (KBr): mmax 3441, 2909, 1719, 1380,
(c 0.5, CHCl3).
4.1.19. ((4R,5R)-5-((S)-Methoxy(phenyl)methyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)methanol 21
Compound 21 was prepared starting from 20 (86% overall
yield for two steps, colorless oil) in the same way as 13a. 1H
NMR (CDCl3, 300 MHz) : d 1.22 (s,3H), 1.32 (s, 3H), 2.82 (m,
1H), 3.08 (dd, J = 3.02, 370 Hz, 1H), 3.30 (s, 3H), 3.70 (m, 1H),
4.05 (dd, J = 6.7, 8.3 Hz, 1H), 4.25 (d, J = 6.7 Hz, 1H), 7.25–7.36
(m, 5H). 13C NMR (CDCl3, 75 MHz): d 26.0, 29.0, 56.0, 62.0,
78.0, 79.0, 85.0, 109.0, 127.0, 128.0, 136.0. IR (KBr): mmax 3462,
1109, 1057, 757 cmꢀ1
.
HRMS calcd for C14H16O4 [M+Na]+
271.0946. Found: 271.0945, ½a D25
¼ þ23:4 (c 0.35, CHCl3).
ꢁ
Acknowledgement
B.M.R. thanks UGC, New Delhi for financial assistance.
References
2987, 1455, 1375, 1097, 860, 705 cmꢀ1
. HRMS calcd for
C14H20O4 [M+Na]+ 275.1259. Found: 175.1250. ½a 2D5
¼ þ55:9 (c
ꢁ
2.1, CHCl3).
4.1.20. (4S,5R)-4-(Iodomethyl)-5-((S)-methoxy(phenyl)methyl)-
2,2-dimethyl-1,3-dioxolane 22
1. Bermejo, A.; Lora, M. J.; Blazquez, M. A.; Rao, K. S.; Cortes, D.; ZafraPolo, M. C.
Nat. Prod. Lett. 1995, 117–122.
Compound 22 was prepared starting from 21 (90%, colorless oil)
in the same way as 14a. 1H NMR (CDCl3, 200 MHz) : d 1.33 (s, 3H),
1.46 (s, 3H), 2.37 (dd, J = 5.46, 10.93 Hz, 1H), 2.71(dd, J = 3.12,
10.15 Hz, 1H), 3.27 (s, 3H), 3.42–3.54 (m, 1H), 3.93(t, J = 7.03 Hz,
1H), 4.23 (d, J = 6.25 Hz, 1H), 4.23 (d, J = 6.25 Hz, 1H), 7.25–7.46
(m, 5H). 13C NMR (CDCl3, 75 MHz): d 6.9, 27.1, 27.3, 56.5, 76.1,
83.4, 85.0, 109.4, 127.5, 128.6, 128.9, 136.4. IR (KBr): mmax 2987,
2. Jean-Phillippe, S.; Jean-Micheal, V. Tetrahedron 1999, 55, 13011–13028.
3. Fang, X. P.; Anderson, J. E.; Qiu, X. X.; Kozlowski, J. F.; Chang, C. J.; Mclaughlin, J.
L. Tetrahedron 1993, 49, 1563–1570.
4. Wang, S.; Zhang, Y. J.; Chen, R. Y.; Yu, D. Q. J. Nat. Prod. 2002, 65, 835–841.
5. Kan, W. S. Pharmaceutical Botany: National Research Institute of Chinese
Medicine: Taipei, 1979, p 247.
6. Lan, Y. H.; Chang, F. R.; Yu, J. H.; Yang, Y. L.; Chang, Y. L.; Lee, S. J.; Wu, Y. C. J.
Nat. Prod. 2003, 66, 487–490.
7. Fang, X. P.; Anderson, J. E.; Chang, C. J.; Fanwick, P. E.; McLaughlin, J. L. J. Chem.
Soc., Perkin Trans. 1 1990, 1655.
8. (a) Deligny, M.; Carreaux, F.; Carboni, B. Synlett 2005, 1462; (b) Shing, T. K. M.;
Tsui, H. Ch.; Zhou, Z. H. J. Org. Chem. 1995, 60, 3121–3130; (c) Prasad, K. R.;
Shivajirao, L. G. Tetrahedron Lett. 2007, 48, 4679–4682.
9. Carreaux, F.; Favre, A.; Carboni, B.; Rouaud, I.; Boustie, J. Tetrahedron Lett. 2006,
47, 4545.
1455, 1375, 1097, 860, 705, 520 cmꢀ1
. (LC–MS): m/z 401
[M+Na]+. ½a 2D5
¼ þ63:1 (c 1.0, CHCl3).
ꢁ
4.1.21. (1R,2S)-2-Methoxy-1-((R)-oxiran-2-yl)-2-phenylethanol
23
10. Yadav, J. S.; Madhava Rao, B.; Sanjeeva Rao, K.; Subbareddy, B. V. Synlett 2008,
1039–1041.
Compound 23 was prepared starting from 22 (70%, colorless oil)
same as 15a. 1H NMR (CDCl3, 300 MHz): d 2.45–2.52 (m, 2H), 2.70
(dd, J = 3.0, 3.7 Hz, 1H), 3.25 (s, 3H), 3.62 (dd, J = 2.2, 7.5 Hz, 1H),
4.13 (d, J = 7.5 Hz, 1H), 7.30 (m, 5H). 13C NMR (CDCl3, 75 MHz): d
45.0, 52.0, 57.0, 75.0, 86.0, 127.0, 128.0, 129.0, 138.0. IR (KBr): mmax
3424, 2927, 1724, 1453, 1102, 760, 701 cmꢀ1. HRMS calcd for
11. Long, D. D.; Smith, M. D.; Martín, A.; Wheatley, J. R.; Watkin, D. G.; Müller, M.;
Fleet, G. W. J. J. Chem. Soc., Perkin Trans. 1 2002, 1982.
12. Babjak, M.; Kapitán, P.; Gracza, T. Tetrahedron 2005, 61, 2471.
13. Wu, W.; Wu, Y. J. Org. Chem. 1993, 58, 3586–3588.
14. Yun, H.; Chou, T. C.; Dong, H.; Tian, Y.; Li, Y. M.; Danishefsky, S. J. J. Org. Chem.
2005, 70, 10375–10380.