Formal synthesis of herbarumin III

Article abstract of DOI:10.1016/j.tetasy.2007.07.022

An enantioselective synthesis of herbarumin III is described employing Jacobsen's hydrolytic kinetic resolution and Sharpless asymmetric dihydroxylation as the key steps.

Full text of DOI:10.1016/j.tetasy.2007.07.022

Tetrahedron: Asymmetry 18 (2007) 1688–1692
Formal synthesis of herbarumin III
Priti Gupta and Pradeep Kumar*
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411 008, India
Received 6 June 2007; accepted 18 July 2007
Abstract—An enantioselective synthesis of herbarumin III is described employing Jacobsen’s hydrolytic kinetic resolution and Sharpless
asymmetric dihydroxylation as the key steps.
ꢀ 2007 Published by Elsevier Ltd.
1. Introduction
As part of our ongoing research program aimed at develop-
ing the enantioselective syntheses of naturally occurring
lactones6 and amino alcohols,7 we herein report an enan-
tioselective synthesis of herbarumin III using hydrolytic ki-
netic resolution and Sharpless asymmetric dihydroxylation
as the key steps.
During the search for a potential herbicidal agent from
Mexican biodiversity, Mata et al. isolated a phytotoxic lac-
tone herbarumin III along with two other known lactones,
herbarumin I, and herbarumin II (Fig. 1).1a Herbarumin
III showed a relevant phytotoxic effect when tested against
seedlings of Amaranthus hypochondriacus.1b It inhibited
radical growth with higher potency than 2,4-dichlorophen-
oxy acetic acid, used as positive control. Compounds 1–3
interacted with bovine-brain calmodulin and inhibited the
activation of the calmodulin-dependent enzyme camp
phosphodiesterase.
2. Results and discussion
Our synthetic strategy for the synthesis of herbarumin III 3
is outlined in Scheme 1. The main fragment, alcohol 16
could be derived from the base induced reductive elimina-
tion of 13, which in turn would be prepared from diol 10.
Diol 10 was obtained by the Sharpless asymmetric dihydr-
oxylation of olefin 9, which in turn could be prepared from
epichlorohydrin 4.
HO
O
R1
R2
HO
O
OH
OPMB
Ref. 2
O
1 R1 = OH, R2 = H; Herbarumin I
2 R1 = R2 = OH; Herbarumin II
3 R1 = R2 = H; Herbarumin III
16
O
3
Figure 1.
OTBS
O
OTBS OH
O
O
In the literature various synthetic approaches have been
reported for herbarumin III. The syntheses described so
far for 3 derive the asymmetry either from chiral pool
materials such as glucose2 and glyceraldehyde,3 by a
chemoenzymatic method4 or by the Sharpless asymmetric
epoxidation.5
I
13
OEt
OEt
10
O
OH
AD
OTBS
OTBS
O
HKR
8
4
9
Cl
*
Corresponding author. Tel.: +91 20 25902050; fax: +91 20 25902629;
e-mail: pk.tripathi@ncl.res.in
Scheme 1. Retrosynthetic analysis of herbarumin III.
0957-4166/$ - see front matter ꢀ 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2007.07.022

P. Gupta, P. Kumar / Tetrahedron: Asymmetry 18 (2007) 1688–1692
1689
In designing a route to 3, we chose racemic epichlorohydrin
as an appropriate starting material. Thus, racemic epichlo-
rohydrin 4 was subjected to Jacobsen’s HKR by using
(R,R)-salen-Co-OAc catalyst to give (S)-epichlorohydrin
(S)-4 as a single isomer, which was easily isolated from
the more polar diol (R)-5 by distillation8 (Scheme 2).
ment with sodium iodide furnished iodide 13 in 85% yield.
Iodide 13, on reductive fragmentation using Zn powder in
refluxing ethanol furnished allylic alcohol 14 in 92% yield,
which was protected as PMB ether followed by subsequent
TBS deprotection to give alcohol 16 in 87% yield. As the
synthesis of 3 from 16 has already been reported,2b the for-
mal synthesis of herbarumin III was completed (Scheme 3).
OH
a
O
O
+
Cl
Cl
Cl
OH
3. Conclusion
4
(S)- 4
(R)-5
In conclusion, a formal synthesis of herbarumin III with
high enantioselectivity has been accomplished in which
the stereocenters were established by Jacobsen’s hydrolytic
kinetic resolution and Sharpless asymmetric dihydroxyla-
tion. Further application of this methodology to the syn-
theses of all the isomers of herbarumin and other
biologically active compounds for structure–activity rela-
tionship studies is currently underway in our laboratory.
Scheme 2. Reagents and conditions: (a) (R,R)-salen-Co-III-(OAc)
(0.5 mol %), dist. H2O (0.55 equiv), 0 ꢁC, 19 h, 46% for (S)-4, 45% for
(R)-5.
Thus, epichlorohydrin (S)-4 was opened with vinylmagne-
sium bromide, followed by base treatment to give epoxide 6
in 90% yield. Epoxide 6 was opened with propylmagnesium
bromide9 to afford homoallylic alcohol 7 in 78% yield,
which was protected as TBS ether to furnish 8 in 94% yield.
Olefin 8 was oxidized to the aldehyde in the presence of
OsO4 and NaIO4 followed by reaction with (ethoxycarbon-
ylmethylene)-triphenylphosphorane in benzene under
reflux conditions to furnish trans-olefin 9 in 89% yield.
The dihydroxylation of 9 with osmium tetroxide and
potassium ferricyanide as co-oxidant in the presence of
(DHQD)2PHAL ligand under the AD conditions10 gave
diol 10 in 95% yield and >96% de.11 Treatment of diol 10
with 2,2-dimethoxypropane in the presence of p-TSA gave
compound 11 in 91% yield, which upon reduction with DI-
BAL-H furnished alcohol 12 in 88% yield. The alcohol 12
was converted into an O-tosyl derivative which on treat-
4. Experimental
4.1. General experimental
Solvents were purified and dried by standard procedures
prior to use; petroleum ether of boiling range 60–80 ꢁC
was used. Optical rotations were measured using a sodium
D line on a JASCO-P-1020-polarimeter. Infrared spectra
were recorded on Perkin–Elmer FT-IR spectrometer. The
enantiomeric excess was measured using either the chiral
HPLC or by comparison with the specific rotation.
OTBS
O
OP
e
O
O
a
d
b
Cl
OEt
OH
9
6
7) P = H
(S)-4
c
8) P = TBS
OTBS
O
OH
O
OTBS
OTBS
O
O
h
f
g
OEt
OEt
10
12
11
O
OH
O
OTBS OPMB
OTBS
O
k
OTBS OH
j
i
I
15
13
14
O
HO
OH
OPMB
Ref. 2b
O
16
O
3
Scheme 3. Reagents and conditions: (a) (i) vinylmagnesium bromide, ether, CuI, ꢀ73 to ꢀ40 ꢁC, 19 h, 72%; (ii) KOH, 90%; (b) C3H7MgBr, THF, CuI,
ꢀ20 ꢁC, 4 h, 78%; (c) TBSCl, imidazole, CH2Cl2, 0 ꢁC to rt, 2.5 h, 94%; (d) (i) OsO4, NaIO4, 2,6-lutidine, 1,4-dioxane/H2O (3:1), 0 ꢁC; (ii)
Ph3P = CHCO2Et, benzene, reflux, 6 h, 84% from two steps; (e) (DHQD)2PHAL, K2CO3, K3Fe(CN)6, MeSO2NH2, OsO4 (0.1 M in toluene), t-BuOH/
H2O (1:1), 0 ꢁC, 24 h, 95%; (f) p-TSA, 2,2-DMP, CH2Cl2, 1.5 h, 91%; (g) DIBAL-H, CH2Cl2, 0 ꢁC to rt, 2 h, 88%; (h) (i) TsCl, Et3N, CH2Cl2, 2 h; (ii) NaI,
2-butanone, reflux, 6 h, 85% for both the steps; (i) Zn, EtOH, reflux, 3 h, 92%; (j) PMBBr, NaH, THF, 90%; (k) TBAF, THF, 8 h, 87%.

1690
P. Gupta, P. Kumar / Tetrahedron: Asymmetry 18 (2007) 1688–1692
Elemental analyses were carried out with a Carlo Erba
CHNS–O analyzer.
using Pet ether/EtOAc (9:1) as eluent provided alcohol 7
25
as a colorless liquid (4.24 g, 78%). ½aꢁD ¼ ꢀ17:4 (c 1.1,
CHCl3); IR (CHCl3, cmꢀ1): 3425, 3019, 2927, 2106, 1601,
1493, 1455, 1251, 1123, 863, 758; 1H NMR (CDCl3,
500 MHz): 5.74–5.79 (m, 1H), 5.02–5.11 (m, 2H), 3.54–
3.59 (m, 1H), 2.34 (br s, 1H), 2.02–2.11 (m, 2H), 1.30–
1.54 (m, 4H), 0.91 (t, J = 6.6 Hz, 3H); 13C NMR (CDCl3,
100 MHz): 135.5, 117.2, 71.1, 42.2, 38.9, 19.2, 14.1.
4.2. Synthesis of (S)-epichlorohydrin (S)-4
The racemic epichlorohydrin 4 was resolved to (S)-epichlo-
rohydrin (S)-4 in high enantiomeric excess by the HKR
25
method following a literature procedure.8d ½aꢁD ¼ þ30:6
26
(c 1.2, MeOH); lit.8d for (R)-epichlorohydrin ½aꢁD
¼
ꢀ32:8 (c 1.27, MeOH).
4.5. Synthesis of (R)-tert-butyl(hept-1-en-4-yloxy)dimeth-
ylsilane 8
4.3. Synthesis of (S)-2-allyloxirane 6
To a stirred solution of alcohol 7 (4.0 g, 35.03 mmol) in
CH2Cl2 (25 mL), imidazole (3.58 g, 52.54 mmol) was
added. To this solution t-butylchlorodimethylsilane
(5.81 g, 38.53 mmol) was added at 0 ꢁC and reaction stirred
at room temperature for 2.5 h. The reaction mixture was
quenched with a saturated aqueous solution of NH4Cl
and extracted with CH2Cl2 (3 · 50 mL). The extract was
washed with brine, dried over Na2SO4, and concentrated.
Silica gel column chromatography of the crude product
A round bottomed flask was charged with copper(I) iodide
(0.103 g, 0.54 mmol), gently heated under vacuum, and
slowly cooled with a flow of argon, after which dry diethyl
ether (30 mL) was added. This suspension was cooled into
ꢀ20 ꢁC and vigorously stirred, after which vinylmagnesium
bromide (1 M in THF, 108 mL, 108.08 mmol) was injected
to it. A solution of epichlorohydrin (S)-4 (5 g, 54.04 mmol)
in diethyl ether (10 mL) was added slowly to the above re-
agent, and the mixture stirred at ꢀ73 ꢁC to ꢀ40 ꢁC for
19 h. The reaction mixture was quenched with a saturated
aqueous solution of NH4Cl. The organic layer was washed
with brine, dried over Na2SO4, and concentrated to afford
the crude homoallylic alcohol, which on vacuum distilla-
tion provided homoallylic alcohol (S)-1-chloropent-4-en-
using Pet ether/EtOAc (49:1) as eluent provided 8 (7.52 g,
25
94%) as a light yellow liquid. ½aꢁD ¼ ꢀ21:2 (c 1.0, CHCl3);
IR (CHCl3, cmꢀ1): 3086, 2972, 2921, 2892, 1640, 1493,
1
1453, 1359, 1248, 1075, 1002, 916, 872; H NMR (CDCl3,
400 MHz): 5.75–5.86 (m, 1H), 5.02–5.12 (m, 2H), 3.74–3.82
(m, 1H), 2.22–2.36 (m, 2H), 2.05–2.18 (m, 1H), 1.62–1.71
(m, 1H), 1.32–1.59 (m, 2H), 0.92 (t, J = 6.6 Hz, 3H), 0.89
(s, 9H), 0.06 (s, 6H); 13C NMR (CDCl3, 100 MHz):
135.2, 116.8, 70.9, 41.1, 40.8, 25.6, 18.2, 17.8, 14.3, ꢀ4.5;
Anal. Calcd for C13H28OSi (228.45): C, 68.35; H, 12.35.
Found: C, 68.24; H, 12.38.
2-ol as a colorless liquid (4.7 g, 72%). Bp 66–69 ꢁC/
25
21 mm of Hg; ½aꢁD ¼ þ5:2 (c 1.4, CHCl3); IR (CHCl3,
cmꢀ1): 3400, 3078, 2931, 2975, 1562, 1457, 1432, 1243,
1071, 914; 1H NMR (CDCl3, 400 MHz): 5.74–5.87 (m,
1H), 5.08–5.19 (m, 2H), 3.85–3.90 (m, 1H), 3.54 (d,
J = 8.1 Hz, 2H), 2.34 (t, J = 8.1 Hz, 2H); 13C NMR
(CDCl3, 100 MHz): 133.2, 118.1, 70.4, 48.9, 38.4.
4.6. Synthesis of (R,E)-ethyl 5-(tert-butyldimethylsilyl-
oxy)oct-2-enoate 9
KOH (2.8 g, 49.76 mmol) was added to the homoallylic
alcohol (5 g, 41.47 mmol) in a flask fitted with a distillation
head. The mixture was heated and epoxide 6 distilled over
To a solution of compound 8 (4 g, 17.51 mmol) in dioxane–
water (3:1, 40 mL) were added 2,6-lutidine (4.1 mL,
35.02 mmol), OsO4 (0.1 M solution in toluene, 3.5 mL,
0.35 mmol), and NaIO4 (14.98 g, 70.04 mmol). The reac-
tion was stirred at 25 ꢁC for 3 h. After the reaction was
complete, water (10 mL) and CH2Cl2 (20 mL) were added.
The organic layer was separated, and the water layer ex-
tracted with CH2Cl2 (3 · 15 mL). The combined organic
layer was washed with brine and dried over Na2SO4 to give
the crude aldehyde, which was used as such for the next
step without further purification.
as
a colorless liquid (3.14 g, 90%). Bp 80–82 ꢁC;
27
½aꢁD ¼ ꢀ16:2 (neat); IR (CHCl3, cmꢀ1): 2995, 1647, 1410,
920; 1H NMR (CDCl3, 200 MHz): 5.68–5.92 (m, 1H),
5.03–5.22 (m, 2H), 2.91–3.03 (m, 1H), 2.73 (dd, J = 5.0,
4.0 Hz, 1H), 2.48 (dd, J = 5.0, 2.6 Hz), 2.23–2.37 (m, 2H);
13C NMR (CDCl3, 50 MHz): 133.0, 117.5, 51.1, 46.4, 36.4.
4.4. Synthesis of (R)-hept-1-en-4-ol 7
A round bottomed flask was charged with copper(I)-iodide
(0.91 g, 0.48 mmol), gently heated under vaccum and
slowly cooled with a flow of argon after which THF
(20 mL) was added. This suspension was cooled to
ꢀ30 ꢁC, stirred, and ethylmagnesium bromide [prepared
from Mg (2.31 g, 95.10 mmol) and ethyl bromide
(10.36 g, 95.10 mmol) in THF] added to it. A solution of
epoxide 6 (4.0 g, 47.55 mmol) in THF (10 mL) was added
to the above reagent and the mixture was stirred at
ꢀ20 ꢁC for 4 h. After consumption of starting material,
the reaction mixture was quenched with a saturated aque-
ous solution of NH4Cl. The water layer was extracted with
EtOAc (3 · 100 mL). The combined organic layer was
washed with brine, dried over Na2SO4, and concentrated.
Silica gel column chromatography of the crude product
To a solution of (ethoxycarbonylmethylene)triphenyl-
phosphorane (7.85 g, 22.57 mmol) in dry benzene
(150 mL) was added a solution of the above aldehyde in
dry benzene (100 mL). The reaction mixture was refluxed
for 6 h. It was then concentrated and purified by silica
gel column chromatography using petroleum ether/EtOAc
(8.5:1.5) as eluent to afford the a,b-unsaturated ester 9
25
(4.42 g, 84%) as a pale yellow liquid. ½aꢁD ¼ ꢀ23:1 (c 1.1,
CHCl3); IR (neat): mmax 3056, 3019, 2962, 2916, 1712,
1
1661, 1472, 1463, 1372, 1269, 1182, 1094 cmꢀ1; H NMR
(200 MHz, CDCl3): d 6.89–7.05 (m, 1H), 5.80 (dt,
J = 15.7, 14.3, 1.4 Hz, 1H), 4.21 (q, J = 7.1 Hz, 2H),
3.72–3.83 (m, 1H), 2.30–2.40 (m, 2H), 1.39–1.50 (m, 4H),
1.29 (t, J = 7.1 Hz, 3H), 0.92 (t, J = 6.6 Hz, 3H), 0.89 (s,

P. Gupta, P. Kumar / Tetrahedron: Asymmetry 18 (2007) 1688–1692
1691
9H), 0.05 (s, 6H); 13C NMR (50 MHz, CDCl3): d 166.3,
145.9, 123.1, 71.0, 59.9, 40.1, 39.4, 25.7, 18.4, 17.9, 14.1,
ꢀ4.7; Anal. Calcd for C16H32O3Si (300.51): C, 63.95; H,
10.73. Found C, 63.88; H, 10.81.
5.58 mmol, 1 M in toluene) through a syringe. The reaction
mixture was allowed to warm to room temperature over
2 h, then re-cooled to 0 ꢁC and treated with a saturated
solution of sodium potassium tartrate. The solid material
was filtered through a pad of Celite and concentrated. Sil-
ica gel column chromatography of the crude product using
4.7. Synthesis of (2S,3R,5R)-ethyl 5-(tert-butyldimethyl-
silyloxy)-2,3-dihydroxyoctanoate 10
petroleum ether/EtOAc (17:3) as eluent gave alcohol 12
25
(1.48 g, 88%) as a colorless liquid. ½aꢁD ¼ ꢀ16:2 (c 1.1,
To a mixture of K3Fe(CN)6 (6.57 g, 19.97 mmol), K2CO3
(2.76 g, 19.97 mmol), and (DHQD)2PHAL (52 mg,
1 mol %), in t-BuOH/H2O (1:1, 35 mL) cooled at 0 ꢁC
was added OsO4 (0.27 mL, 0.1 M sol in toluene,
0.4 mol %) followed by methanesulfonamide (0.63 g,
6.66 mmol). After stirring for 5 min at 0 ꢁC, olefin 9
(2.0 g, 6.66 mmol) was added in one portion. The reaction
mixture was stirred at 0 ꢁC for 24 h and then quenched
with solid sodium sulfite (10 g). The stirring was continued
for 45 min and the solution was extracted with EtOAc
(3 · 50 mL). The combined organic phases were washed
with brine, dried over Na2SO4 and concentrated. Silica
gel column chromatography of the crude product using
CHCl3); IR (neat): mmax 3459, 3021, 2958, 2946, 1720,
1469, 1374, 1265, 1221, 1164, 1047, 963, 942 cmꢀ1 1H
;
NMR (200 MHz, CDCl3): d 4.14–3.97 (m, 2H), 3.81 (d,
J = 7.2 Hz, 2H), 3.78–3.63 (m, 1H), 1.73–1.62 (m, 2H),
1.60–1.44 (m, 2H), 1.43 (s, 3H), 1.41 (s, 3H), 1.40–1.38
(m, 2H), 0.94 (t, J = 6.6 Hz, 3H), 0.89 (s, 9H), 0.06 (s,
6H); 13C NMR (50 MHz, CDCl3): d 108.6, 81.7, 73.6,
69.6, 61.9, 40.9, 38.6, 26.9, 25.8, 18.6, 17.7, 14.3, ꢀ4.36;
Anal. Calcd for C17H36O4Si (332.55): C, 61.40; H, 10.91.
Found C, 61.52; H, 10.89.
4.10. Synthesis of ((R)-1-((4R,5S)-5-(iodomethyl)-2,2-
dimethyl-1,3-dioxolan-4-yl)pentan-2-yloxy)(tert-
butyl)dimethylsilane 13
petroleum ether/EtOAc (3:2) as eluent gave diol 10
25
(2.12 g, 95%) as a colorless syrupy liquid. ½aꢁD = ꢀ11.2 (c
1.0, CHCl3); IR (neat): mmax 3446, 3018, 2958, 2898, 2412,
To a stirred solution of alcohol 12 (1.4 g, 4.21 mmol) in
CH2Cl2 (40 mL) at 0 ꢁC under nitrogen was added tri-
ethyl-amine (1.65 mL, 11.82 mmol), followed by tosyl chlo-
ride (0.90 g, 4.73 mmol). After being stirred for 2 h at room
temperature, the reaction mixture was diluted with H2O,
and extracted with CH2Cl2 (50 mL). The combined organic
layers were washed with water, brine, and dried over
Na2SO4. The solvent was removed under reduced pressure
to give the tosylate as a pale yellow oil, which was used as
such for the next step, without further purification.
1
1733, 1665, 1465, 1261, 1092 cmꢀ1; H NMR (200 MHz,
CDCl3): d 4.28 (q, J = 7.1 Hz, 2H), 4.02–4.12 (m, 2H),
3.96 (d, J = 4.2 Hz, 1H), 3.09 (br s, 2H), 1.63–1.82 (m,
2H), 1.49–1.56 (m, 2H), 1.32 (t, J = 7.1 Hz, 3H), 0.95 (t,
J = 6.6 Hz, 3H), 0.90 (s, 9H), 0.10 (s, 6H); 13C NMR
(50 MHz, CDCl3): d 173.2, 74.1, 71.2, 69.4, 61.7, 39.9,
38.7, 25.8, 17.9, 17.9, 14.2, 14.1, ꢀ4.6; Anal. Calcd for
C16H34O5Si (334.52): C, 57.45; H, 10.24. Found C, 57.36;
H, 10.21.
4.8. Synthesis of (4S,5R)-ethyl 5-((R)-2-(tert-butyldimethyl-
silyloxy)pentyl)-2,2-dimethyl-1,3-dioxolane-4-carboxylate
11
The tosylate (2.05 g, 4.21 mmol) was dissolved under argon
in dry 2-butanone (20 mL) and treated with NaI (1.89 g,
12.65 mmol). The reaction mixture was refluxed for 6 h.
After cooling to room temperature the volatiles were re-
moved under reduced pressure. Silica gel column chroma-
tography of the crude product using petroleum ether/
To a solution of diol 10 (2.0 g, 5.98 mmol), p-TSA (50 mg)
in CH2Cl2 (50 mL) was added 2,2-dimethoxypropane
(0.93 g, 1.1 mL, 8.97 mmol) and the mixture stirred for
1.5 h. Solid NaHCO3 was added and stirred. The reaction
was filtered through a pad of neutral alumina and concen-
trated. Silica gel column chromatography of the crude
EtOAc (19:1) as eluent gave iodo compound 13 (1.58 g,
25
85%) as a light yellow liquid. ½aꢁD ¼ ꢀ64:7 (c 1.0, CHCl3);
IR (neat): mmax 3020, 2965, 2932, 2856, 1522, 1468, 1384,
1
1298, 1211, 1028, 968 cmꢀ1; H NMR (200 MHz, CDCl3):
product using petroleum ether/EtOAc (9:1) gave 11
d 3.95–3.83 (m, 2H), 3.65–3.53 (m, 1H), 3.35–3.19 (m, 2H),
1.84–1.64 (m, 2H), 1.62–1.41 (m, 4H), 1.44 (s, 3H), 1.41 (s,
3H), 0.95 (t, J = 6.6 Hz, 3H), 0.91 (s, 9H), 0.07 (s, 6H); 13C
NMR (50 MHz, CDCl3): d 108.9, 80.1, 78.2, 69.5, 40.6,
38.5, 27.3, 27.2, 25.9, 18.6, 18.0, 14.4, 5.41, ꢀ4.29, ꢀ4.60;
Anal. Calcd for C17H35IO3Si (442.45): C, 46.15; H, 7.97.
Found C, 46.22; H, 7.90.
25
(2.04 g, 91%) as a colorless liquid. ½aꢁD ¼ ꢀ24:1 (c 0.8,
CHCl3); IR (neat): mmax 3021, 2952, 2946, 1742, 1664,
1471, 1375, 1216, 1135, 1078, 964, 856 cmꢀ1 1H NMR
;
(200 MHz, CDCl3): d 4.22 (q, J = 7.1 Hz, 2H), 4.03–4.14
(m, 2H), 3.85–3.94 (m, 1H), 1.80–1.94 (m, 2H), 1.61–1.74
(m, 2H), 1.46 (s, 3H), 1.44 (s, 3H), 1.36–1.39 (m, 2H),
1.30 (t, J = 7.1 Hz, 3H), 0.92 (t, J = 6.6 Hz, 3H), 0.88 (s,
9H), 0.06 (s, 6H); 13C NMR (50 MHz, CDCl3): d 170.7,
110.7, 79.2, 76.1, 69.3, 61.2, 41.1, 40.4, 38.7, 27.2, 25.8,
18.4, 17.9, 14.3, 14.1, ꢀ4.53; Anal. Calcd for C19H38O5Si
(374.59): C, 60.92; H, 10.23. Found C, 61.04; H, 10.18.
4.11. Synthesis of (3R,5R)-5-(tert-butyldimethylsilyloxy)oct-
1-en-3-ol 14
A
mixture of 13 (1.5 g, 3.39 mmol), zinc (0.44 g,
6.78 mmol) in refluxing ethanol (15 mL) under nitrogen
was stirred for 3 h. The zinc was filtered and filtrate con-
centrated. Silica gel column chromatography of the crude
4.9. Synthesis of ((4R,5R)-5-((R)-2-(tert-butyldimethylsilyl-
oxy)pentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methanol 12
product using petroleum ether/EtOAc (9:1) as eluent gave
25
To a solution of ester 11 (1.9 g, 5.07 mmol) in dry CH2Cl2
(20 mL) at 0 ꢁC was added dropwise DIBAL-H (5.58 mL,
14 (0.81 g, 92%) as a light yellow liquid. ½aꢁD ¼ ꢀ32:1 (c
1.0, CHCl3); IR (neat): mmax 3445, 3082, 3958, 2932, 2858,

1692
P. Gupta, P. Kumar / Tetrahedron: Asymmetry 18 (2007) 1688–1692
1645, 1472, 1464, 1379, 1256, 1216, 1127, 1066, 922,
836 cmꢀ1 1H NMR (200 MHz, CDCl3): d 5.87 (dq,
(50 MHz, CDCl3): d 159.3, 138.3, 129.9, 124.5, 117.5,
113.9, 81.2, 71.1, 69.8, 55.2, 42.5, 39.8, 18.6, 14.1; Anal.
Calcd for C16H24O3 (264.36): C, 72.62; H, 9.19. Found
C, 72.54; H, 9.28.
;
J = 17.1, 11.9, 6.7, 1.0 Hz, 1H), 5.23 (dd, J = 17.1, 15.5,
1.6 Hz, 1H), 5.07 (dd, J = 11.9, 10.36, 1.51 Hz, 1H),
4.32–4.23 (m, 1H), 4.15–3.92 (m, 1H), 1.68–1.63 (m, 2H),
1.55–1.48 (m, 2H), 1.37–1.23 (m, 2H), 0.94 (t, J = 6.6 Hz,
3H), 0.91 (s, 9H), 0.11 (s, 6H); 13C NMR (50 MHz,
CDCl3): d 140.9, 113.9, 71.8, 69.6, 43.0, 40.1, 25.8, 18.7,
17.8, 14.2, ꢀ4.10, ꢀ4.73; Anal. Calcd for C14H30O2Si
(258.47): C, 65.06; H, 11.70. Found C, 65.11; H, 11.81.
Acknowledgments
P.G. thanks UGC, New Delhi, for financial assistance in
the form of a research fellowship. We are grateful to Dr.
M. K. Gurjar for his support and encouragement. The
financial support from DST, New Delhi (Grant No. SR/
S1/OC-40/2003) is gratefully acknowledged. This is NCL
communication No. 6703.
4.12. Synthesis of tert-butyl-((4R,6R)-6-(4-methoxybenzyl-
oxy)oct-7-en-4-yloxy)dimethylsilane 15
To a solution of 14 (0.50 g, 1.93 mmol) in dry THF
(20 mL) was added sodium hydride (50%, 0.11 g,
2.32 mmol) at 0 ꢁC. The reaction mixture was then stirred
at room temperature for 30 min after which it was again
cooled to 0 ꢁC. To this was added slowly p-methoxybenzyl
bromide (0.36 g, 2.13 mmol) and tetra n-butylammonium
iodide (0.71 g, 0.19 mmol) with further stirring for 1 h at
the same temperature. The reaction mixture was quenched
with addition of cold water and EtOAc at 0 ꢁC. The two
phases were separated and the aqueous phase was extracted
with EtOAc (3 · 100 mL). The combined organic layers
were washed with water (3 · 100 mL), brine, dried over
Na2SO4 and concentrated. The residual oil was purified
by silica gel column chromatography using petroleum
References
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ether/EtOAc (8:2) as eluent to furnish 15 (0.66 g, 90%) as
25
a colorless oil. ½aꢁD ¼ ꢀ38:3 (c 1.1, CHCl3); IR (neat): mmax
3085, 2951, 2936, 2847, 1641, 1487, 1464, 1378, 1247, 1121,
1
1055, 913, 839 cmꢀ1; H NMR (200 MHz, CDCl3): d 7.22
(d, J = 8.2 Hz, 2H), 6.88 (d, J = 8.3 Hz, 2H), 5.82–5.65
(m, 1H), 5.26–5.19 (m, 2H), 4.32 (s, 2H), 4.04–3.99 (m,
1H), 3.98–3.94 (m, 1H), 3.79 (s, 3H), 1.68–1.61 (m, 2H),
1.48–132 (m, 4H), 0.92 (t, J = 6.9 Hz, 3H), 0.90 (s, 9H),
0.09 (s, 6H); 13C NMR (50 MHz, CDCl3): d 159.1, 139.6,
129.7, 129.5, 116.9, 114.1, 81.7, 72.3, 71.6, 55.3, 43.9,
40.4, 25.9, 18.7, 17.6, 14.3, ꢀ4.3, ꢀ4.6; Anal. Calcd for
C22H38O3Si (378.62): C, 69.79; H, 10.12. Found C, 69.65;
H, 10.16.
4.13. Synthesis of (4R,6R)-6-(4-methoxybenzyloxy)oct-7-en-
4-ol 16
To a solution of 15 (0.65 g, 1.72 mmol) in THF (10 mL)
was added TBAF (2.58 mL, 2.58 mmol, 1.0 M solution in
THF) at room temperature. The reaction mixture was stir-
red for 8 h and then diluted with water and extracted with
EtOAc. The organic layer was washed with brine, dried
over Na2SO4, and concentrated. The crude product was
purified by column chromatography on silica gel (hexane/
EtOAc, 3:1) to give 16 (0.395 g, 87%) as a colorless oil.
25
½aꢁD ¼ ꢀ9:6 (c 0.80, CHCl3); IR (neat): mmax 3448, 3073,
2985, 2931, 2852, 1634, 1469, 1445, 1257, 1221, 1127,
1
918, 834 cmꢀ1; H NMR (200 MHz, CDCl3): d 7.21 (d,
J = 8.2 Hz, 2H), 6.84 (d, J = 8.3 Hz, 2H), 5.84–5.66 (m,
1H), 5.29–5.21 (m, 2H), 4.54 (d, J = 11.1 Hz, 1H), 4.26
(d, J = 11.2 Hz, 2H), 4.06–4.01 (m, 1H), 4.0–3.96 (m,
1H), 3.80 (s, 3H), 3.59 (br s, 1H), 1.69–1.60 (m, 2H),
1.44–1.26 (m, 2H), 0.94 (t, J = 6.9 Hz, 3H); 13C NMR
10. (a) Becker, H.; Sharpless, K. B. Angew. Chem., Int. Ed. 1996,
35, 448–451; (b) Kolb, H. C.; Van Nieuwenhze, M. S.;
Sharpless, K. B. Chem. Rev. 1994, 94, 2483–2547.
11. Diastereomeric excess was determined from 1H and 13C
NMR spectra data.