Stereoselective synthesis of the polyketide chain of nagahamide A

Article abstract of DOI:10.1016/j.tetasy.2006.09.025

A carbohydrate based approach for the enantioselective synthesis of the polyketide acid unit present in nagahamide A has been reported. Reductive ring opening of a chiral cyclopropane ketone group to enantioselectively install the methyl and propyl groups

Full text of DOI:10.1016/j.tetasy.2006.09.025

Tetrahedron: Asymmetry 17 (2006) 2609–2616
Stereoselective synthesis of the polyketide chain of nagahamide A
Debendra K. Mohapatra,* Siddhartha Ray Chaudhuri,
Gokarneswar Sahoo and Mukund K. Gurjar*
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411 008, India
Received 27 June 2006; revised 11 September 2006; accepted 21 September 2006
Abstract—A carbohydrate based approach for the enantioselective synthesis of the polyketide acid unit present in nagahamide A has
been reported. Reductive ring opening of a chiral cyclopropane ketone group to enantioselectively install the methyl and propyl groups,
is a salient feature of this synthesis.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
The off-template organo-metallic mediated C–C bond
forming reactions at C-5 on sugar furanoses are well docu-
mented for their excellent stereocontrolled behaviour.4
However, the off-template reduction of a double bond sit-
uated at C-5 to install, for instance, a methyl group, has
never been very successful in terms of stereochemically,
and invariably results in a mixture of diastereomers.5 In
our opinion, no attempts have been made to develop an
appropriate strategy, by which enatioselectively an alkyl
group at C-5 can be installed. Herein we report an organo-
metallic mediated route via a regioselective ring opening
reaction of a cyclopropyl6 group to introduce methyl
and alkyl groups simultaneously and which goes on to
Nagahamide A 1 was isolated from the marine sponge
Theonella swinhoei and shown to posses antibacterial activ-
ity.1 The structure of nagahamide A is characterized by a
six amino acid peptide backbone joined together in a mac-
rocyclic structure that incorporates a novel polyketide
chain 2. The polyketide ester 2 of nagahamide A 1 contains
four contiguous stereogenic centres and a terminal E,E-die-
noic ester group. Compound 2 is closely related to the
naturally occurring YM 47522 3,2 except for the stereo-
chemical configuration of the terminal E,Z-dienoic acid
group.3
Me
Me
O
1
9
7
OMe
13
Me
Me
Me
HN
Me
Me
8
Me
O
O
11
5
3
H
O
OMe
Polyketide chain 2
Me
TBSO
N
O
N
H
NH2
O
HO
O
O
O
NH2
O
MeO
HN
Me
HO
OH
NH
H
O
OH
YM 47522 3
O
N
O
O
Nagahamide A 1
*
Corresponding authors. Tel.: +91 20 25902627; fax: +91 20 25902629 (D.K.M.); e-mail: dk.mohapatra@ncl.res.in
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.09.025

2610
D. K. Mohapatra et al. / Tetrahedron: Asymmetry 17 (2006) 2609–2616
synthesise, for the first time, the polyketide side chain 2 of
nagahamide A 1.
single product. Although its absolute stereochemistry could
not be determined at this stage, we believe that the influ-
ence of the C-3 and C-4 substituents would allow the entry
of a methylene group from the a-face. This contention was
substantiated at a later stage.
2. Results and discussion
Gratifyingly, compound (Z)-12 also underwent cycloprop-
anation with the same reagents, as described above, to pro-
duce 9, identical with the sample obtained above in a 67%
yield. These results could be explained by the mechanism
of the cyclopropanation reaction, which first involved a
Michael type of 1,4-addition followed by cyclisation.
In order to investigate the stereocontrolled cyclopropana-
tion reaction, the 3-O-benzyl-1,2:5,6-di-O-isopropylidine-
a-D-glucofuranose 10 was converted to the aldehyde7
derivative 11 in two steps and then subjected to a reaction
with acetonyltriphenylphosphorane to give a 60:40 mixture
of E/Z-isomers [(E)-12 and (Z)-12] of the unsaturated
ketone derivative in a 60% yield; these were conveniently
1
The radical ring opening reaction of 9 with n-Bu3SnH9
gave a linear product 13, whose structure was confirmed
separated by silica gel chromatography. In the H NMR
spectrum of (E)-12, the olefinic protons appeared as a set
1
by H NMR, 13C NMR and elemental analysis. On the
of two double-doublets at 6.37 ppm (J6,4 = 1.5 Hz, J6,5
=
other hand, reduction10 of 9 with a 10% Pd/C at 200 psi
at 60 ꢁC predominantly gave compound 8 along with com-
pound 15 as a minor product (Scheme 3). Compound 15,
whose structure was supported by spectroscopic and ana-
lytical data, seemed to have formed by the over reduction
of 9. It is gratifying to note that reduction of 9 at room
temperature gave 8 as the only product in a 78% yield.
Reaction of 8 with p-TSA in methanol gave the corres-
ponding methyl ketal derivative 14, which was prepared
to support the structure of 8 using NMR experiments
(Fig. 1).
16.2 Hz) and 6.76 ppm (J5,4 = 5.4 Hz, J5,6 = 16.2 Hz),
thereby confirming the trans-stereochemistry. On the other
hand, the H NMR spectrum of (Z)-12 showed that the
olefinic protons resonated as multiplets between 6.17 and
6.33 ppm. All the other protons resonated at their expected
chemical shift values (see Scheme 1).
1
Major isomer (E)-12 was treated with trimethylsulfoxo-
nium iodide8 in the presence of NaH to afford the cyclopro-
1
pane derivative 9 (Scheme 2) in a 62% yield. The H and
13C NMR spectra clearly indicated the formation of a
Me
Me
Me
Me
Me
OMe
OH
O
OMe
OMe
TBSO
TBSO
Me
4
2
Me
Me
Me
OH
O
O
OH
O
O
OMe
TBSO
O
O
O
5
6
7
O
O
Me
O
O
OBn
O
O
O
OBn
O
Me
O
OH
O
O
O
9
8
10
Scheme 1. Retrosynthetic analysis.
O
O
Me
OBn
O
O
c
O
O
O
O
OHC
O
O
OBn
a
(E)-12
(Z)-12
b
OBn
O
+
OBn
O
O
O
c
Me
O
O
O
OBn
O
11
10
O
9
O
Scheme 2. Reagents and conditions: (a) Ref. 7; (b) Ph3P+CH2COCH3Brꢀ, Na2CO3, dioxane–H2O (3:1), MeOH, 100 ꢁC, 2 h, (60%); (c) NaH,
(CH3)3S+OIꢀ, DMSO, 10 ꢁC, {62% from (E)-12 and 67% from (Z)-12}.

D. K. Mohapatra et al. / Tetrahedron: Asymmetry 17 (2006) 2609–2616
2611
O
O
NMR spectrum of 17, the characteristic signals due to
the TBS group were located in the up-field region. The
13C NMR spectroscopy and elemental analysis were in full
agreement with the assigned structure 17. In order to install
the methyl group at C-3, a conventional sequence of oxida-
tion, Wittig reaction, and catalytic hydrogenation were
adopted in order to obtain 19. The removal of the TBS
group followed by the Barton McCombie radical deoxy-
genation13 gave 6, whose structure was fully characterized
O
OBn
a
O
OBn
O
O
O
O
O
13
9
Me
O
Me
O
O
OBn
H
H
H
H
b
O
O
O
O
+
1
O
by spectroscopy and elemental analysis. In the H NMR
Me
Me
O
O
O
OR
spectrum of 6, a characteristic triplet due to the H-2 proton
was observed at 4.49 ppm (J = 4.4 Hz) indicating that the
H-2 was cis to both H-1 and H-3. Due to the 1,2-isopro-
pylidine group, the hydrogenation of the C3-exo-methylene
group was expected to occur from the b-face. The charac-
teristic two doublets observed at 0.84 ppm (J = 6.6 Hz) and
1.01 ppm (J = 6.6 Hz) were attributed to methyl groups
present at C-5 and C-3. Other resonances were in good
agreement with the assigned structure 6. The structure
was further confirmed by its 13C NMR spectroscopy and
elemental analysis. The stereocentre at C-3 was further
confirmed by NOE studies (Fig. 3). Strong NOEs were
observed between the protons at C-1 (5.71 ppm) and C-2
(4.49 ppm), C-2 (4.49 ppm) and C-3 (1.82 ppm). No NOE
was found between the protons at C-3 (1.82 ppm) and
C-4 (3.69 ppm); a relevant NOE was observed between
the methyl group at C-3 (1.01 ppm) with the proton at
C-4 (3.69 ppm) suggesting the anti configuration. Treat-
ment of 6 with 6 M HCl opened the isopropylidene ring
and produced lactol 22 (Scheme 4).
9
8
R = H
15
c
14 R = Me
Scheme 3. Reagents and conditions: (a) n-Bu3SnH, cat. AIBN, toluene,
reflux, 3 h, (82%); (b) 10% Pd/C, EtOAc, 200 psi, 60 ꢁC, 20 h, 8 (65%) and
15 (20%); (c) MeOH, p-TSA (cat.), 0 ꢁC, 2 h, (85%).
Me
H
H
O
Me
O
O
OMe H
O
Figure 1. NOE studies on 14.
The assignment of the absolute stereochemistry at the C-5
centre of cyclopropane derivative 9 was further determined
based on single crystal X-ray crystallographic11,12 studies
of the debenzylated product 16. The ORTEP diagram of
16 (Fig. 2) revealed that the cyclopropanation occurred
from the a-face.
The Wittig reaction of 22 with Ph3P@CH2 gave the termi-
nal olefinic product 23. The characteristic signals due to the
1
terminal olefin in the H NMR spectrum of 23 supported
the assigned structure. To assign the stereocentres at C-3,
C-4, C-5 further, the diol 23 was protected as its acetonide
derivative 24. In the 13C NMR of acetonide 24, the appear-
ance of the acetonide methyl groups C-7, C-8 at 19.6, 30.2,
respectively, and the quaternary carbon C-6 at 97.9 clearly
suggests the syn nature of the C-3 and C-5 hydroxyl
groups.14 Nuclear Overhauser effect (NOE) experiments
allowed us to assign the absolute configuration further at
C-3, C-4 and C-5. As shown in Figure 4, a relevant NOE
was observed between the protons at C-3 (3.85 ppm) and
C-5 (3.46 ppm). Strong NOEs were observed between
the methyl group at C-4 (0.72 ppm) with the protons at
C-3 and C-5. The axial acetonide methyl group C-7
(1.38 ppm) also had a strong NOE with the protons at
C-3 and C-5. The above studies enabled us to assign the
stereocentres at C-3, C-4 and C-5 as (S), (S) and (R),
respectively. The higher reactivity of allylic hydroxyl group
was exploited to selectively block with a methyl group
using MeI–LiHMDS to give 25 (Scheme 5). In the 1H
NMR spectra of 25, the resonance due to H-3 was clearly
apparent as a triplet whereas the chemical shifts of all the
other protons were comparable except for H-3 which
showed an upfield shift of 0.56 ppm. The second hydroxyl
group of 25 was first silylated and then treated with Me2S–
BH3 to afford compound 4.
Our next concern involved the introduction of a methyl
group at the C-3 centre for which compound 8 was reduced
with LiAlH4 to provide a (1:1) diastereomeric mixture
(based on 1H NMR and 13C NMR spectra) of diol 7
(Scheme 4). It is pertinent to mention that the newly
formed C-7 stereocentre of 7 was of no consequence, as it
would finally be destroyed. Therefore, we decided to con-
tinue our synthetic strategy with a mixture. The less hin-
dered secondary hydroxyl group of 7 was protected as its
1
TBS ether 17 by using TBSCl and imidazole. In the H
Finally, compound 4 was oxidized with the Dess–Martin
periodinane15 and subjected to a Wittig reaction with
Figure 2. ORTEP diagram of 16.

2612
D. K. Mohapatra et al. / Tetrahedron: Asymmetry 17 (2006) 2609–2616
Me
OR
Me
TBSO
Me
OR
O
O
OH
O
e
c, d
a
8
O
O
O
O
Me
O
O
18
7 R = H
17 R = TBS
b
19 R = TBS
20 R = H
21 R = CS2SMe
f
g
h
Me
Me
O
O
OH
i
O
Me
22
OH
O
Me
6
Scheme 4. Reagents and conditions: (a) lithium aluminium hydride, THF, 0 ꢁC–rt, 1 h, (92%); (b) TBSCl, imidazole, CH2Cl2, 0 ꢁC–rt, 0.5 h, (90%);
(c) (COCl)2, DMSO, CH2Cl2, Et3N, ꢀ78 ꢁC, (97%); (d) Ph3P@CH2, THF, ꢀ15 ꢁC, (75%); (e) 10% Pd/C, EtOAc, 2 h, (91%); (f) TBAF, THF, 0 ꢁC, 0.5 h,
(90%); (g) NaH, CS2, CH3I, 0 ꢁC–rt, (75%); (h) n-Bu3SnH, cat. AIBN, toluene, reflux, 3 h, (73%); (i) 6 M HCl, THF–H2O (3:1), cat. H2SO4, 70 ꢁC, 1 h,
(70%).
1
spectroscopic data. For example, its H NMR spectrum
revealed signals due to the olefin protons at d 5.80 (d,
J2.3 = 15.2 Hz), 7.28 (dd, J3,2 = 15.2 Hz, J3,4 = 9.9 Hz),
6.22 (dd, J4,3 = 9.9 Hz, J4,5 = 15.1 Hz) and 6.18 (dt,
J5,4 = 15.1 Hz, J5,6 = 7.4 Hz) which were characteristic of
the E,E-dienoic group.
C3H7
6
CH3
O
5
4
H
O
1
H
H
O
9
CH3
H
3
2
7
CH3
10
CH3
8
3. Conclusion
Figure 3. Some NOESY interactions for 6.
In conclusion, the first enantioselective synthesis of naga-
hamide A side chain 2 from D-glucose has been accom-
plished. Further work on peptide synthesis is in progress
in our laboratory.
H
Me
6
7
H
5
H
8
Me
3
O
Me
9
O
4
CH2
1
4. Experimental
4.1. General
Me
H
C3H7
Figure 4. Some NOESY interactions for 24.
All chemicals used in this study were purchased from
Aldrich, Fluka, or Lancaster and used as received. All
the moisture-sensitive reactions were performed under an
(EtO)2P(O)CH2–CH@CH–COOMe16 to give the polyke-
tide side chain 2. The structure of 2 was investigated by
Me Me
Me Me
a
b
22
O
O
OH
OH
23
24
c
Me Me
OR2
Me Me
Me Me
TBSO
e
OH
f
OMe
OR1
TBSO
OMe
OMe
O
25 R1 = Me, R2 = H
R1 = Me, R2 = TBS
2
d
4
5
Scheme 5. Reagents and conditions: (a) Ph3P@CH2, THF, ꢀ78 ꢁC–rt, 10 h, (71%); (b) DMP, p-TSA, acetone, rt, 3 h, (97%); (c) LiHMDS, CH3I, THF,
ꢀ78 to 0 ꢁC, 1 h, (83%); (d) TBSOTf, lutidine, CH2Cl2, 0 ꢁC–rt, 1 h, (80%); (e) H3B–SMe2, NaOAc, H2O2, 0 ꢁC–rt, 6 h (60%); (f) (i) Dess–Martin
periodinane, pyridine, CH2Cl2, rt, 30 min, (85%); (ii) (EtO)2P(O)CH2CH@CHCO2Me, LiHMDS, THF, ꢀ78 ꢁC, 1 h, (82%).

D. K. Mohapatra et al. / Tetrahedron: Asymmetry 17 (2006) 2609–2616
2613
inert atmosphere of either N2 or Ar using dry solvents. The
elemental analyses were recorded on Elmentar-Vario-EL
(Heraeus Company Ltd, Germany). The NMR spectra
were obtained on a Bruker 200, 400 or 500 Fourier trans-
form spectrometer. The optical rotations were measured
with a JASCO DIP 370 digital polarimeter. All reactions
are monitored by Thin Layer Chromatography (TLC) car-
ried out on 0.25 mm E-Merck silica gel plates (60F-254)
with UV, I2 or anisaldehyde in ethanol as development
reagents.
d 1.19 (ddd, 1H, J = 4.1, 6.6, 9.3 Hz), 1.33 (s, 3H), 1.37 (dt,
1H, J = 4.4, 9.3 Hz), 1.47 (s, 3H), 1.90 (dt, 1H, J = 4.4,
8.3 Hz), 1.94–1.98 (m, 1H), 2.16 (s, 3H), 3.72 (dd, 1H,
J = 3.4, 7.5 Hz), 3.85 (d, 1H, J = 3.2 Hz), 4.54 (d, 1H,
J = 11.9 Hz), 4.63 (d, 1H, J = 4.0 Hz), 4.71 (d, 1H, J =
11.9 Hz), 5.92 (d, 1H, J = 4.0 Hz), 7.29–7.37 (m, 5H); 13C
NMR (50 MHz, CDCl3): d 15.4, 21.2, 25.0, 25.7, 26.3,
29.6, 71.4, 81.7 (2C), 82.1, 104.3, 110.8, 127.3, 127.5,
128.1, 137.1, 206.0. Anal. Calcd for C19H24O5: C, 68.65;
H, 7.27. Found: C, 68.46; H, 7.10.
4.1.1. 3-O-Benzyl-5,6,8-trideoxy-1,2-O-isopropylidene-a-D-
xylo-oct-5Z-enofuranos-7-ulose (Z)-12 and 3-O-benzyl-
5,6,8-trideoxy-1,2-O-isopropylidene-a-D-xylo-oct-5E-enofu-
ranos-7-ulose (E)-12. A solution of acetonyl-triphenyl-
phophonium bromide (62.0 g, 155.5 mmol) and Na2CO3
(16.5 g, 155.5 mmol) in dioxane/H2O (3:1, 120 mL) was
heated at reflux for 45 min and then 11 (24.0 g, 91.5 mmol)
in MeOH (30 mL) was added dropwise. After 2 h, the reac-
tion mixture was concentrated, the residue dissolved in
ethyl acetate, washed with saturated aqueous Na2CO3
solution, dried over Na2SO4 and concentrated. The residue
was stirred with hexane (300 mL) and ethyl acetate (15 mL)
for 1 h, filtered and the filtrate concentrated. The residue
4.1.3.
5,6-C-Methylene-5,6,8-trideoxy-1,2-O-isopropylid-
ene-L-glycero-b-L-iodo-octos-7-ulofuranose 16. Compound
9 (0.085 g, 0.26 mmol) in MeOH was hydrogenated using
10% Pd in charcoal at atmospheric pressure. After 4 h,
the reaction mixture was filtered through a small Celite pad.
The filtrate was concentrated and purified by column
chromatography using ethyl acetate and light petroleum
ether (1:3) to afford 16 as a crystalline solid (0.059 g,
95%), which was again recrystallised from CH2Cl2 and light
25
petroleum ether. Mp. 135–136 ꢁC; ½aꢁD ¼ þ49:4 (c 1.0,
CHCl3); 1H NMR (200 MHz, CDCl3): d 1.19–1.36 (m,
2H), 1.30 (s, 3H), 1.47 (s, 3H), 1.75 (m, 1H), 2.00 (m,
1H), 2.25 (s, 3H), 2.61 (br s, 1H), 3.86 (dd, 1H, J = 2.6,
6.3 Hz), 4.12 (d, 1H, J = 2.6 Hz), 4.52 (d, 1H,
J = 3.7 Hz), 5.88 (d, 1H, J = 3.7); 13C NMR (50 MHz,
CDCl3): d 15.09, 21.13, 24.77, 26.01, 26.61, 30.26, 75.91,
81.13, 85.10, 104.55, 111.13, 208.04. Anal. Calcd for
C12H18O5: C, 59.49; H, 7.49. Found: C, 59.67; H, 7.56.
was purified on silica gel using ethyl acetate and light petro-
25
leum (1:9) to furnish (Z)-12 (7.0 g, 24%), ½aꢁD ¼ ꢀ37:2 (c
1
0.8, CHCl3); H NMR (200 MHz, CDCl3): d 1.32 (s, 3H),
1.50 (s, 3H), 2.20 (s, 3H), 3.35 (d, 1H, J = 3.4 Hz), 4.42
(d, 1H, J = 11.7 Hz), 4.56 (d, 1H, J = 12.2 Hz), 4.60 (d,
1H, J = 3.9 Hz), 5.44 (dd, 1H, J = 3.4, 5.4 Hz), 5.98 (d,
1H, J = 3.9 Hz), 6.17–6.33 (m, 2H), 7.23–7.34 (m, 5H);
13C NMR (50 MHz, CDCl3): d 26.1, 26.5, 30.6, 71.8,
78.4, 82.8, 84.0, 104.8, 111.2, 127.1, 127.2, 127.3, 127.9,
137.2, 143.1, 197.7. Anal. Calcd for C18H22O5: C, 67.90;
H, 6.96. Found: C, 67.73; H, 6.76.
4.1.4. 3-O-Benzyl-5,6,7,9-tetradeoxy-1,2-O-isopropylidene-
a-D-xylo-nonos-8-ulofuranose 13. A solution of 9 (0.2 g,
0.6 mmol), tri-n-butyltin hydride (0.2 mL, 0.7 mmol) and
AIBN (15 mg) in benzene (10 mL) under argon was heated
at reflux for 3 h and concentrated. A saturated solution of
KF and ether were introduced, stirred vigorously for 4 h
and the ether layer separated, dried over Na2SO4 and con-
centrated. The residue was purified on silica gel using ethyl
acetate and light petroleum (3:17) to obtain 13 (0.16 g,
82%). ½aꢁD ¼ ꢀ56:6 (c 1.0, CHCl3); H NMR (200 MHz,
CDCl3): d 1.31 (s, 3H), 1.48 (s, 3H), 1.58–1.70 (m, 4H),
1.12 (s, 3H), 2.42–2.48 (m, 2H), 3.76 (d, 1H, J = 2.9 Hz),
4.06–4.13 (m, 1H), 4.47 (d, 1H, J = 12.2 Hz), 4.59 (d, 1H,
J = 3.9 Hz), 4.70 (d, 1H, J = 12.2 Hz), 5.88 (d, 1H,
J = 3.9 Hz), 7.25–7.31 (m, 5H); 13C NMR (50 MHz,
CDCl3): d 20.4, 26.1, 26.6, 27.3, 29.7, 43.4, 71.6, 80.0,
82.2 (2C), 104.6, 111.1, 127.6, 127.8, 128.3, 137.5, 207.9.
Anal. Calcd for C19H26O5: C, 68.24; H, 7.83. Found: C,
67.98; H, 7.74.
25
Further elution gave (E)-12 (10.5 g, 36%), ½aꢁD ¼ ꢀ63:7
1
(c 0.5, CHCl3); H NMR (200 MHz, CDCl3): d 1.33 (s,
3H), 1.49 (s, 3H), 2.27 (s, 3H), 3.97 (d, 1H, J = 3.4 Hz),
4.46 (d, 1H, J = 12.2 Hz), 4.65 (d, 1H, J = 12.2 Hz), 4.66
(d, 1H, J = 3.9 Hz), 4.78 (ddd, 1H, J = 1.6, 3.4, 5.4 Hz),
5.99 (d, 1H, J = 3.9 Hz), 6.37 (dd, 1H, J = 1.5, 16.2 Hz),
6.76 (dd, 1H, J = 5.4, 16.2 Hz), 7.23–7.36 (m, 5H); 13C
NMR (50 MHz, CDCl3): d 26.1, 26.7, 27.3, 72.0, 79.5,
82.6, 83.1, 104.9, 111.8, 127.6, 128.0, 128.4, 131.6, 136.9,
140.1, 197.2. Anal. Calcd for C18H22O5: C, 67.90; H,
6.96. Found: C, 67.85; H, 6.68.
25
1
4.1.2.
3-O-Benzyl-5,6-C-methylene-5,6,8-trideoxy-1,2-O-
9.
isopropylidene-L-glycero-b-L-iodo-octos-7-ulofuranose
To a suspension of NaH (1.79 g, 60% dispersion in oil,
45.0 mmol), trimethyl sulfoxonium iodide (9.9 g, 45.0
mmol) in DMSO (50 mL) under argon at 10 ꢁC was added
(E)-12 (13.0 g, 40.9 mmol) in DMSO (50 mL) over a period
of 30 min. The reaction was quenched with ice-cold water
and extracted with ethyl acetate. The combined organic
layer was washed with water, dried over Na2SO4 and con-
centrated. The residue was purified on silica gel using ethyl
acetate and light petroleum (1.5:8.5) to afford 9 (8.41 g,
62%). Similarly, starting from (Z)-12 and following the
above procedure gave compound 9 in a 67% yield.
4.1.5. 3,7-Anhydro-5-C-methyl-5,6,8-trideoxy-1,2-O-isoprop-
ylidene-L-glycero-b-L-iodo-octofuranose 15 and (7 R/S)-
5,6,8-trideoxy-1,2-O-isopropylidene-5-C-methyl-b-L-iodo-
octos-7-ulo-1,4-furano-3,7-pyranose 8. A solution of 9
(3.0 g, 9.0 mmol) in ethyl acetate (25 mL) was hydroge-
nated in the presence of 10% Pd/C (0.3 g) at 200 psi at
60 ꢁC. After 20 h, the reaction mixture was filtered through
a pad of Celite, concentrated and the residue purified on
silica gel using ethyl acetate and light petroleum (1:9) to
25
1
afford 15 (0.41 g, 20%), ½aꢁD ¼ þ11:8 (c 1.0, CHCl3); H
NMR (500 MHz, CDCl3): d 1.08 (d, 3H, J = 7.6 Hz),
1.12 (d, 3H, J = 6.1 Hz), 1.20–1.23 (m, 1H), 1.30 (s, 3H),
25
1
½aꢁD ¼ þ7:2 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3):

2614
D. K. Mohapatra et al. / Tetrahedron: Asymmetry 17 (2006) 2609–2616
25
1.49 (s, 3H), 1.67–1.73 (m, 1H), 2.23–2.28 (m, 1H), 3.58–
3.64 (m, 1H), 3.83 (s, 1H), 3.98 (d, 1H, J = 1.6 Hz), 4.45
(d, 1H, J = 3.6 Hz), 5.88 (d, 1H, J = 3.6 Hz); 13C NMR
(50 MHz, CDCl3): d 16.6, 21.3, 25.6, 26.2, 27.0, 33.5,
65.7, 76.0, 77.5, 83.7, 104.4, 110.4. Anal. Calcd for
C12H20O4: C, 63.13; H, 8.83. Found: C, 63.41; H, 8.60.
Further elution gave slower moving isomer, ½aꢁD ¼ þ23:4
1
(c 0.9, CHCl3); H NMR (200 MHz, CDCl3): d 0.09, 0.10
(2s, 6H), 0.90 (s, 9H), 1.12 (d, 3H, J = 6.8 Hz), 1.19 (d,
3H, J = 5.9 Hz), 1.30 (s, 3H), 1.32 (m, 2H), 1.50 (s, 3H),
1.54–1.67 (m, 1H), 1.92–2.02 (m, 1H), 3.49 (br s, 1H),
3.76 (dd, 1H, J = 2.4, 10.2 Hz), 4.03–4.20 (m, 1H), 4.52
(d, 1H, J = 3.9 Hz), 5.90 (d, 1H, J = 3.9 Hz); 13C NMR
(50 MHz, CDCl3): d ꢀ4.7, ꢀ4.5, 17.5, 18.0, 24.7, 25.8,
26.0, 26.6, 28.3, 43.0, 66.4, 74.2, 84.9, 85.6, 104.2, 110.6.
Anal. Calcd for C18H36O5Si: C, 59.96; H, 10.06. Found:
C, 59.83; H, 9.79.
Further elution afforded 8 (1.43 g, 65%), 1H NMR
(500 MHz, CDCl3): d 1.15 (d, 3H, J = 7.2 Hz), 1.21 (s,
3H), 1.25 (s, 3H), 1.26 (dd, 1H, J = 5.8, 13.4 Hz), 1.49 (s,
3H), 1.65 (dd, 1H, J = 5.2, 13.4 Hz), 1.70–1.76 (m, 1H),
3.90 (t, 1H, J = 3.4 Hz), 4.05 (d, 1H, J = 3.4 Hz), 4.42 (d,
1H, J = 3.9 Hz), 5.78 (d, 1H, J = 3.9 Hz); 13C NMR
(50 MHz, CDCl3): d 17.5, 22.6, 27.2, 28.0, 30.1, 36.4,
74.0, 79.8, 83.5, 96.0, 104.5, 111.0. Anal. Calcd for
C12H20O5: C, 59.00; H, 8.25. Found: C, 58.87; H, 8.54.
4.1.8. 7-O-tert-Butyldimethylsilyl-3,5-C-dimethyl-3,5,6,8-
tetradeoxy-1,2-O-isopropylidene-D/L-glycero-b-L-talo-octo-
furanose 19. Dry DMSO (2.6 mL, 36.7 mmol) and oxa-
loyl chloride (1.6 mL, 18.3 mmol) in CH2Cl2 (20 mL) at
ꢀ78 ꢁC under N2 were stirred for 30 min and then 17
(4.4 g, 12.2 mmol) in CH2Cl2 (10 mL) was added. After
1 h, the reaction was quenched by Et3N (7.7 mL) at
ꢀ78 ꢁC and worked up as usual. The residue (4.24 g,
97%) was dissolved in anhydrous THF (20 mL) and cooled
to ꢀ78 ꢁC. Methylenetriphenylphosphorane [prepared from
PPh3CH3I (9.5 g) and n-BuLi (1.6 M, 15.0 mL)] were
added. After 2 h stirring at rt, it was quenched by addition
of saturated aqueous NH4Cl solution. The two layers were
separated, the organic layer dried over Na2SO4 and con-
centrated to form a residue which was purified on silica
gel using ethyl acetate and light petroleum (1:19) to furnish
the olefin 18 (3.16 g, 75%).
4.1.6. (7S)-Methyl-5-C-methyl-5,6,8-trideoxy-1,2-O-isoprop-
14.
ylidene-b-L-iodo-octos-7-ulo-1,4-furano-3,7-pyranose
A solution of 8 (0.2 g, 0.8 mmol) and p-TSA (15 mg) in
MeOH (10 mL) was stirred at 0 ꢁC for 2 h, neutralized
with Et3N and concentrated. The residue was partitioned
between ethyl acetate and water, the organic layer dried
(Na2SO4), concentrated and chromatographed on silica
gel with ethyl acetate and light petroleum (1:19) to provide
25
1
14 (0.18 g, 85%). ½aꢁD ¼ þ122:7 (c 1.0, CHCl3); H NMR
(500 MHz, CDCl3): d 1.18 (d, 3H, J = 7.5 Hz), 1.29 (s,
3H), 1.33 (s, 3H), 1.41 (dd, 1H, J = 6.0, 13.9 Hz), 1.51 (s,
3H), 1.78 (dd, 1H, J = 5.1, 13.9 Hz), 1.93–2.00 (m, 1H),
3.22 (s, 3H), 3.94 (t, 1H, J = 3.2 Hz), 4.01 (d, 1H,
J = 3.2 Hz), 4.56 (d, 1H, J = 3.8 Hz), 5.90 (d, 1H,
J = 3.8 Hz); 13C NMR (50 MHz, CDCl3): d 19.3, 23.1,
26.2, 26.7, 28.3, 36.9, 48.1, 72.8, 80.7, 84.4, 99.3, 105.0,
111.3. Anal. Calcd for C13H22O5: C, 60.44; H, 8.58. Found:
C, 60.27; H, 8.65.
The above product (3.10 g, 8.7 mmol), 10% Pd/C (0.3 g) in
EtOAc (20 mL) was stirred under hydrogen at normal tem-
perature and pressure. After 2 h, the reaction mixture was
filtered through a pad of Celite and concentrated. The res-
idue was purified on silica gel using ethyl acetate and light
1
petroleum (1:19) to provide 19 (2.83 g, 91%). H NMR
(200 MHz, CDCl3): d 0.04, 0.05 (2s, 6H), 0.84 (d, 3H,
J = 7.3 Hz), 0.88 (s, 9H), 1.01 (d, 3H, J = 6.6 Hz), 1.13
(d, 3H, J = 6.3), 1.31 (s, 3H), 1.40–1.60 (m, 2H), 1.49 (s,
3H), 1.76–1.90 (m, 2H), 3.76 (dd, 1H, J = 2.2, 10.2 Hz),
3.89–3.96 (m, 1H), 4.50 (t, 1H, J = 3.9 Hz), 5.71 (d, 1H,
J = 3.9 Hz); 13C NMR (50 MHz, CDCl3): d ꢀ4.5, ꢀ3.9,
9.5 and 9.6, 14.1 and 14.4, 18.1, 24.2 and 24.4, 26.0, 26.4,
26.7, 29.4, 39.6, 44.6 and 44.7, 66.5 and 66.7, 83.1, 83.8,
104.5, 110.9. Anal. Calcd for C19H38SiO4: C, 63.64; H,
10.68. Found: C, 63.48; H, 10.59.
4.1.7. 7-O-tert-Butyldimethylsilyl-5-C-methyl-5,6,8-tri-de-
oxy-1,2-O-isopropylidene-D/L-glycero-b-L-iodo-octofuranose
17. A stirred suspension of LAH (0.57 g, 15.2 mmol) and
8 (3.7 g, 15.2 mmol) in THF (20 mL) was stirred at rt for
1 h. After the usual workup, the crude product was purified
on silica gel using ethyl acetate and light petroleum (3:7) to
afford 7 (3.43 g, 92%), which was dissolved in dry CH2Cl2
(30 mL). Imidazole (1.89 g, 27.9 mmol) and tert-butyldi-
methylsilyl chloride (2.31 g, 15.3 mmol) were then added.
After 0.5 h, the reaction mixture was washed with satu-
rated NH4Cl solution, water, dried (Na2SO4) and concen-
trated to afford 17 (4.51 g, 90%) and used as such for the
next reaction. For analytic samples, a part of the residue
was chromatographed on silica gel using ethyl acetate
4.1.9. 3,5-C-Dimethyl-3,5,6,7,8-pentadeoxy-1,2-O-isoprop-
ylidene-b-L-talo-octofuranose 6. A solution of 19 (2.70 g,
7.5 mmol) and 1 M solution of n-Bu4NF (8.3 mL,
8.3 mmol) were stirred for 30 min and concentrated. The
crude was extracted with ethyl acetate, washed with water,
dried over Na2SO4, then concentrated. The residue was
chromatographed on silica gel using ethyl acetate and light
petroleum (3:7) to give 20 (1.65 g, 90%). 1H NMR
(200 MHz, CDCl3): d 0.90 (d, 3H, J = 7.3 Hz), 1.03 (d,
3H, J = 6.8 Hz), 1.18 (d, 3H, J = 6.4), 1.32 (s, 3H), 1.49
(s, 3H), 1.52–1.70 (m, 2H), 1.81–1.96 (m, 2H), 2.48 (br s,
1H), 3.83 (dd, 1H, J = 2.0, 10.2 Hz), 3.89–3.99 (m, 1H),
4.52 (t, 1H, J = 3.9 Hz), 5.72 (d, 1H, J = 3.9 Hz); 13C
NMR (50 MHz, CDCl3): d 9.5 and 9.6, 13.4 and 13.5,
and light petroleum (1:9) to elute faster moving isomer,
25
½aꢁD ¼ þ13:0 (c 1.0, CHCl3); 1H NMR (200 MHz, CDCl3):
d 0.09 (s, 6H), 0.90 (s, 9H), 1.04 (d, 3H, J = 6.3 Hz), 1.13
(d, 3H, J = 5.9 Hz), 1.26 (s, 3H), 1.30–1.38 (m, 2H), 1.41
(s, 3H), 1.49–1.61 (m, 1H), 1.87–1.97 (m, 1H), 2.98 (br d,
1H, J = 5.4 Hz), 3.72 (dd, 1H, J = 2.9, 9.8 Hz), 3.97–4.08
(m, 2H), 4.49 (d, 1H, J = 4.0 Hz), 5.83 (d, 1H, J =
4.0 Hz); 13C NMR (50 MHz, CDCl3): d ꢀ4.7, 18.1, 18.8,
22.3, 25.9, 26.0, 26.6, 27.7, 42.0, 67.5, 73.9, 85.2, 85.7,
104.3, 110.7. Anal. Calcd for C18H36O5Si: C, 59.96; H,
10.06. Found: C, 60.25; H, 10.33.

D. K. Mohapatra et al. / Tetrahedron: Asymmetry 17 (2006) 2609–2616
2615
23.9, 26.4, 26.7, 29.8, 39.6, 44.4 and 44.6, 64.6, 83.0, 84.4,
104.4 and 104.5, 111.3.
(ddd, 1H, J = 0.8, 1.8, 17.2), 5.69 (ddd, 1H, J = 7.5, 10.1,
17.2); 13C NMR (50 MHz, CDCl3): d 11.8, 12.5, 14.4,
19.6, 20.5, 30.2, 33.0, 35.1, 36.2, 75.8, 77.4, 97.9, 117.8,
137.7. Anal. Calcd for C14H26O2: C, 74.29; H, 11.58.
Found: C, 74.38; H, 11.71.
The above product 20 (1.54 g, 6.3 mmol) in THF (10 mL)
was added to NaH (0.3 g, 7.6 mmol) in THF (5 mL). The
resulting solution was stirred at rt for 30 min, CS2
(0.6 mL) and MeI (0.6 mL) were added. After usual work
up, the residue was purified on silica gel by using ethyl ace-
tate and light petroleum (1:9) to provide 21 (1.77 g, 75%).
4.1.12. (3S,4S,5R,6S)-5-(tert-Butyl-dimethyl-silanyloxy)-3-
methoxy-4,6-dimethyl-non-1-ene 5. To a solution of 23
(0.2 g, 1.0 mmol) in dry THF (7 mL) at ꢀ78 ꢁC, LiHMDS
(1.06 M, 1.1 mL) was added. After 15 min, MeI (0.1 mL,
1.7 mmol) in THF (0.5 mL) was introduced and the reac-
tion mixture warmed to 0 ꢁC. The reaction mixture was
quenched with saturated aqueous NH4Cl solution and
extracted with ethyl acetate. The organic layer was dried
over Na2SO4 and concentrated to provide a residue which
was purified on silica gel using ethyl acetate and light
The above product 21, n-Bu3SnH (1.5 mL, 5.6 mmol) and
AIBN (15 mg) in toluene (15 mL) under argon were heated
at reflux for 3 h, concentrated and chromatographic purifi-
cation on silica gel using ethyl acetate and light petroleum
25
(3:97) afforded 6 (0.78 g, 73%). ½aꢁD ¼ þ46:7 (c 1, CHCl3);
1H NMR (300 MHz, CDCl3): d 0.84 (d, 3H, J = 6.6 Hz),
0.90 (t, 3H, J = 7.1 Hz), 1.01 (d, 3H, J = 6.6 Hz), 1.31 (s,
3H), 1.33–1.45 (m, 4H), 1.49 (s, 3H), 1.55–1.61 (m, 1H),
1.79–1.84 (m, 1H), 3.69 (dd, 1H, J = 2.2, 10.2 Hz), 4.49
(t, 1H, J = 4.4 Hz), 5.71 (d, 1H, J = 4.4 Hz); 13C NMR
(75 MHz, CDCl3): d 9.5, 13.2, 14.2, 20.5, 26.4, 26.7, 33.0,
36.8, 39.7, 83.1, 84.9, 104.5, 110.8. Anal. Calcd for
C13H24O3: C, 68.38; H, 10.59. Found: C, 68.48; H, 10.64.
petroleum ether (1:19) to afford 25 (0.18 g, 83%).
25
½aꢁD ¼ ꢀ20:7 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3):
d 0.72 (d, 3H, J = 7.3 Hz), 0.84 (d, 3H, J = 6.6 Hz), 0.91 (t,
3H, J = 6.8 Hz), 1.29–1.42 (m, 4H), 1.53–1.63 (m, 1H),
1.70–1.78 (m, 1H), 3.29 (s, 3H), 3.47 (dd, 1H, J = 2.2,
8.8 Hz), 3.52 (t, 1H, J = 8.4 Hz), 4.04 (br s, 1H), 5.20
(dd, 1H, J = 1.8, 17.1 Hz), 5.31 (dd, 1H, J = 1.8,
10.2 Hz), 5.54–5.66 (m, 1H); 13C NMR (75 MHz, CDCl3):
d 11.7, 14.6, 15.4, 21.1, 34.6, 38.6, 43.8, 56.2, 75.2, 79.5,
117.8, 137.5. Anal. Calcd for C12H24O2: C, 71.95; H,
12.07. Found: C, 71.82; H, 11.91.
4.1.10. (3S,4S,5R,6S)-4,6-Dimethyl-non-1-ene-3,5-diol 23.
Compound 6 (0.73 g, 3.2 mmol) and 6 M HCl (2 mL) in
THF–H2O (12:4 mL) were heated at 70 ꢁC for 1 h. The
reaction mixture was neutralized by addition of solid NaH-
CO3, filtered and concentrated. The residue was partitioned
between ethyl acetate and water, the organic layer sepa-
rated, washed with water, dried over Na2SO4 and concen-
trated. The residue was purified on silica gel using ethyl
acetate and light petroleum (1:3) to obtain 22 (0.42 g,
70%) which was dissolved in THF (10 mL) and CH2@PPh3
[prepared from PPh3CH3I (2.7 g) and n-BuLi (1.6 M,
4.0 mL)] at ꢀ78 ꢁC was added. After 10 h of stirring at
rt, it worked up as usual and the residue purified on silica
gel using ethyl acetate and light petroleum (1:4) to furnish
The above product 25 (0.13 g, 0.6 mmol), 2,6-lutidine
(0.3 mL) and TBSOTf (0.22 mL, 0.1 mmol) in CH2Cl2
(4 mL) were stirred at rt for 1 h, washed with water and
concentrated. The residue was purified on silica gel using
ethyl acetate and light petroleum (1:49) to furnish 5
25
(0.16 g, 80%). ½aꢁD ¼ þ3:9 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3) data: d 0.06 (s, 6H), 0.80 (d, 3H,
J = 7.3 Hz), 0.86 (d, 3H, J = 6.6 Hz), 0.89–0.93 (m, 12H),
1.27–1.36 (m, 4H), 1.55–1.63 (m, 1H), 1.83–1.90 (m, 1H),
3.22 (s, 3H), 3.46 (t, 1H, J = 7.6 Hz), 3.80 (dd, 1H,
J = 2.2, 5.8 Hz), 5.16–5.27 (m, 2H), 5.54–5.66 (m, 1H);
13C NMR (75 MHz, CDCl3): d ꢀ4.1, ꢀ3.8, 11.6, 14.4,
15.2, 18.6, 20.7, 26.2, 34.5, 38.4, 43.6, 56.0, 74.0, 84.8,
117.7, 137.3. Anal. Calcd for C18H38SiO2: C, 68.72; H,
12.17. Found: C, 68.70; H, 11.92.
25
1
23 (0.29 g, 71%). ½aꢁD ¼ þ7:7 (c 0.7, CHCl3); H NMR
(300 MHz, CDCl3): d 0.75 (d, 3H, J = 6.6 Hz), 0.85 (d,
3H, J = 7.3 Hz), 0.92 (t, 3H, J = 6.6 Hz), 1.30–1.38 (m,
4H), 1.65–1.75 (m, 2H), 3.35 (br s, 2H), 3.53 (dd, 1H,
J = 2.2, 8.2 Hz), 4.08 (t, 1H, J = 8.0 Hz), 5.16–5.27 (m,
2H), 5.80–5.92 (m, 1H); 13C NMR (75 MHz, CDCl3): d
12.0, 13.0, 14.3, 20.6, 34.7, 36.6, 41.0, 79.0 (2C), 116.5,
139.8. Anal. Calcd for C11H22O2: C, 70.92; H, 11.98.
Found: C, 70.77; H, 12.16.
4.1.13. (3S,4S,5R,6S)-5-(tert-Butyl-dimethyl-silanyloxy)-3-
methoxy-4,6-dimethyl-nonan-1-ol 4. To a solution of 5
(0.11 g, 0.3 mmol) in anhydrous THF (3 mL) at 0 ꢁC was
added H3B–SMe2 (0.1 mL, 1.0 mmol). After stirring for
1 h, saturated NaOAc solution was introduced followed
by the addition of 30% H2O2 (0.1 mL). The reaction mix-
ture was further stirred at rt for 5 h, diluted with ethyl ace-
tate, dried (Na2SO4) and concentrated. The crude was
4.1.11.
(4R,5S,6S)-2,2,5-Trimethyl-4-((S)-pentan-2-yl)-6-
vinyl-1,3-dioxane 24. Diol 23 (0.03 g, 0.16 mmol) in ace-
tone (3 mL) was treated with 2,20-dimethoxypropane
(0.08 mL, 0.64 mmol) and a catalytic amount of p-TSA at
room temperature. After 3 h, the reaction mixture was
quenched with a drop of Et3N. The solvent was evaporated
in vacuo and purified by column chromatography using
purified on silica gel using ethyl acetate and light petroleum
25
(1:9) to provide 4 (70 mg, 60%). ½aꢁD ¼ ꢀ23:9 (c 0.8,
1
CHCl3); H NMR (500 MHz, CDCl3): d 0.05, 0.06 (2s,
light petroleum ether and ethyl acetate (19:1) to give 24
6H), 0.82 (d, 3H, J = 7.2 Hz), 0.87 (d, 3H, J = 6.8 Hz),
0.91–0.93 (m, 12H), 1.17–1.20 (m, 1H), 1.34–1.39 (m,
3H), 1.60–1.65 (m, 1H), 1.66–1.71 (m, 3H), 2.06–2.10 (m,
1H), 3.34 (s, 3H), 3.48 (dd, 1H, J = 2.4, 7.6 Hz), 3.64 (dt,
1H, J = 4.4, 8.4 Hz), 3.78 (t, 2H, J = 5.6 Hz); 13C NMR
(125 MHz, CDCl3): d ꢀ3.7, ꢀ3.4, 11.0, 14.3 (2C), 18.6,
20.9, 26.4, 31.2, 36.2, 37.1, 38.6, 55.2, 61.7, 76.9, 82.5. Anal.
25
(0.036 g, 97%) as a colorless liquid. ½aꢁD ¼ þ25:6 (c 1.3,
CHCl3); 1H NMR (200 MHz, CDCl3): d 0.71 (d, 3H,
J = 6.7 Hz), 0.83 (d, 3H, J = 6.8 Hz), 0.90 (t, 3H,
J = 6.6 Hz), 1.31 (m, 4H), 1.38 (s, 3H), 1.44 (s, 3H), 1.65
(m, 2H), 3.46 (dd, 1H, J = 2.2, 10.2), 3.50 (dd, 1H,
J = 7.4, 10.4), 5.20 (ddd, 1H, J = 0.5, 1.8, 10.1), 5.25

2616
D. K. Mohapatra et al. / Tetrahedron: Asymmetry 17 (2006) 2609–2616
(b) Sugawara, T.; Shibazaki, M.; Nakahara, H.; Suzuki, K.
J. Antibiot. 1996, 49, 345.
Calcd for C18H40SiO3: C, 65.00; H, 12.12. Found: C, 64.73;
H, 12.20.
3. Ermolenko, M. S. Tetrahedron Lett. 1996, 37, 6711.
4. (a) Georges, M.; Tam, T. M.; Fraser-Reid, B. J. Chem. Soc.,
Chem. Commun. 1984, 1122; (b) Hanessian, S. In Total
Synthesis of Natural Products: The Chiron Approach; Perg-
amon Press, 1984; Vol. 3.
5. Gurjar, M. K.; Rajendran, V.; Rao, B. V. Tetrahedron Lett.
1998, 39, 3803.
6. Cousins, G. S.; Hoberg, J. O. Chem. Soc. Rev. 2000, 29, 165.
7. Robins, M. J.; Wnuk, S. F.; Yang, X.; Yuan, C.-S.;
Borchardt, R. T. J. Med. Chem. 1998, 41, 3857.
4.1.14. (7S,8S,9R,10S)-9-(tert-Butyl-dimethyl-silanyloxy)-
7-methoxy-8,10-dimethyl-trideca-2,4-dienoic acid methyl
ester 2. A solution of 4 (45 mg, 0.14 mmol), pyridine
(30 lL) and Dess–Martin periodinane (85 mg) in CH2Cl2
(2 mL) was stirred at rt for 30 min. A saturated solution
of NaHCO3 and Na2S2O3 (1:1, 2 mL) was then added.
The organic layer was separated while the aqueous layer
was extracted with CH2Cl2. The combined organic extract
was dried over Na2SO4, filtered and concentrated to give
crude aldehyde (38 mg, 85%).
8. Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87,
1353.
9. (a) Gurjar, M. K.; Chakrabarti, A.; Rao, B. V.; Kumar, P.
Tetrahedron Lett. 1997, 38, 6885; (b) Gurjar, M. K.; Sarma,
B. V. N. B. S.; Rao, B. V. J. Carbohydr. Chem. 1998, 17, 1107;
(c) Gurjar, M. K.; Kumar, P.; Rao, B. V. Carbohydr. Lett.
2001, 4, 103.
To a solution of methyl 4-(diethylphosphono)crotonate
(60 mg) in anhydrous THF (2 mL) at ꢀ78 ꢁC, LiHMDS
(0.25 mL, 1.0 M) was added. After 1 h, this solution was
transferred via cannula into the above prepared aldehyde
(38 mg) in THF (2 mL) maintained at ꢀ78 ꢁC. The reaction
mixture was warmed to rt, stirred for 1 h and worked up as
usual. The residue was purified on silica gel using ethyl ace-
10. Gurjar, M. K.; Kumar, P.; Rao, B. V. Tetrahedron Lett. 1996,
37, 8617.
11. CCDC 290095, X-ray crystal data: Single crystals of the
complex were grown by slow evaporation of the solution in
dichloromethane. A colourless needle of approximate size
0.2 · 0.15 · 0.16 mm, was used for data collection on Bruker
SMART APEX CCD diffractometer using Mo Ka radiation
with fine focus tube with 50 kV and 30 mA. Crystal to
detector distance 6.05 cm, 512 · 512 pixels/frame, multiscan
data acquisition. Total scans = 4, total frames = 2424, oscil-
lation/frame ꢀ0.3ꢁ, exposure/frame = 20.0 s/frame, maxi-
mum detector swing angle = ꢀ30.0ꢁ, beam centre = (260.2,
252.5), in plane spot width = 1.24, SAINT integration, h
range = 1.56–25.00ꢁ, completeness to h of 25.00ꢁ is 100%.
SADABS correction applied, C12H18O5, M = 242.27. Crys-
tate and light petroleum ether (1:9) to afford a terminal
25
E,E-dienoic ester 2 (39 mg, 82%). ½aꢁD ¼ ꢀ8:0 (c 0.7,
1
CHCl3); H NMR (500 MHz, CDCl3): d 0.01, 0.03 (2s,
6H), 0.81 (d, 3H, J = 7.0 Hz), 0.83 (d, 3H, J = 6.5 Hz),
0.89–0.91 (m, 12H), 1.14–1.20 (m, 1H), 1.28–1.40 (m,
3H), 1.60 (m, 1H), 1.99 (m, 1H), 2.23 (m, 1H), 2.41 (ddd,
1H, J = 2.8, 5.4, 14.7 Hz), 3.29 (s, 3H), 3.38 (ddd, 1H,
J = 2.8, 5.4, 8.5 Hz), 3.58 (dd, 1H, J = 2.3, 6.5 Hz), 3.75
(s, 3H), 5.80 (d, 1H, J = 15.2 Hz), 6.18 (dt, 1H, J = 7.4,
15.1 Hz), 6.22 (dd, 1H, J = 9.9, 15.1 Hz), 7.28 (dd, 1H,
J = 9.9, 15.2 Hz); 13C NMR (125 MHz, CDCl3): d ꢀ3.7,
11.2, 14.4, 14.7, 18.6, 20.9, 26.3, 33.6, 35.7, 37.6, 40.4,
51.3, 56.8, 76.2, 81.2, 119.2, 130.2, 141.1, 145.0, 167.4.
Anal. Calcd for C23H44SiO4: C, 66.94; H, 10.74. Found:
C, 67.15; H, 10.51.
tals belong to orthorhombic, space group P21, a = 5.517(3),
3
˚
˚
b = 9.144(4), c = 26.180(13) A, V = 1320.7(11) A , Z = 4,
Dc = 1.218 mg mꢀ3, l(Mo-Ka) = 0.094 mmꢀ1, T = 295(2) K,
6685 reflections measured, 2337 unique [I > 2r(I)],
R = 0.0472, wR2 = 0.1038. All the data were corrected for
Lorentzian, polarisation and absorption effects. SHELX-97
(SHELXTL)12 was used for structure solution and full matrix
least squares refinement on F2. Hydrogen atoms were
included in the refinement as per the riding model.
12. Sheldrik, G. M. SHELX-97 Program for Crystal Structure
Solution and Refinement; University of Gottingen: Germany,
1997.
Acknowledgements
S.R.C. and G.S. thank CSIR, New Delhi, for a research
grant. We are grateful to Dr. Mohan M. Bhadbhade and
Dr. P. R. Rajmohanan for single crystal X-ray crystallo-
graphic studies and NMR data, respectively.
13. Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin
Trans. 1 1975, 1574.
14. (a) Rychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett.
1990, 31, 945; (b) Evans, D. A.; Rieger, D. L.; Gage, J. R.
Tetrahedron Lett. 1990, 31, 7099.
15. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
16. Methyl-4-(diethylphosphono)crotonate was prepared from
freshly distilled methyl 4-bromocrotonate (5 mL, 42.56
mmol) and triethylphosphite (8.85 mL, 51.07 mmol) at
120 ꢁC for 3 h. The product was isolated by distillation at
130 ꢁC under vacuo (0.4 mm); yield: 3.40 g (83%).
References
1. Okada, Y.; Matsunaga, S.; van Soest, R. W. M.; Fusetani, N.
Org. Lett. 2002, 4, 3039.
2. (a) Shibazaki, M.; Sugawara, T.; Nagai, K.; Shimizu, Y.;
Yamaguchi, H.; Suzuki, K. J. Antibiot. 1996, 49, 340;