Stereoselective total synthesis of iso-cladospolide B

Article abstract of DOI:10.1055/s-2006-950317

A simple and efficient stereoselective total synthesis of iso-cladospolide B and a formal total synthesis of cladospolide B, using Jacobsen's hydrolytic kinetic resolution, is described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950317

PAPER
4041
Stereoselective Total Synthesis of iso-Cladospolide B
S
tereoselectiv
.
T
otal Synth
S
esis of iso-C
l
r
adospoli
i
de
B
hari,* E. Vijaya Bhasker, S. J. Harshavardhan, J. S. Yadav
Organic Division – I, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: srihari@iict.res.in
Received 24 July 2006
OH
OH
Abstract: A simple and efficient stereoselective total synthesis of
iso-cladospolide B and a formal total synthesis of cladospolide B,
using Jacobsen’s hydrolytic kinetic resolution, is described.
O
1
O
Key words: phytotoxic, Wadsworth–Emmons, oxidation, kinetic
resolution, Mitsunobu
OTBDPS
O
COOMe
O
3
O
O
OH
Marine fungi are emerging as a potential source of new
pharmaceuticals and pharmaceutical leads.1 Recently, iso-
cladospolide B (1), obtained from the fermentation of fun-
gal isolate I962S215, was also isolated from ethyl acetate
extracts of cladosporium species and from red sea sponge
Niphates rowi.2 It closely resembles the natural product
cladospolide B (2), a highly phytotoxic compound3 pro-
duced from Cladosporium tenuissimum. Though there
have been two earlier synthesis reported for iso-clado-
spolide B,4 there is still need for a simple, short and effi-
cient synthetic route for further biological studies. Our
group has recently initiated an academic programme fo-
cused on the synthesis of several lactone-containing natu-
ral products5 and their analogues for further evaluation of
their biological properties. As part of this programme,
herein we report the stereoselective total synthesis of iso-
cladospolide B and the formal total synthesis of clado-
spolide B, with Jacobsen’s kinetic resolution and a modi-
fied Wadsworth–Emmons reaction being the key steps.
OTBDPS
O
2
OH
OBn
5
I
OHC
O
4
O
L-(+)-tartaric acid
OBn
6
Figure 1
alcohol 11. The alcohol was coupled with mercaptoben-
zothiazole under Mitsunobu conditions7 to afford the thio-
ether 12 which, on oxidation with MCPBA, resulted in
sulphone 13. Unfortunately, attempts at reacting 13 with
the known aldehyde 5 under Julia conditions8a failed to
give the expected alkene 16 (Scheme 2).8b We therefore
converted the alcohol 11 into the corresponding phospho-
rane salt 15, with the intention of using this as one of the
components in a Wittig reaction with 5. The conversion of
11 to 15 was accomplished using I2, triphenylphosphine
and imidazole,9 followed by treatment of the resulting io-
dide 14 with triphenyl phosphine.
Our retrosynthetic analysis for both iso-cladospolide B
and cladospolide B (Figure 1) revealed a common key in-
termediate 3, which could be prepared by a Wittig reac-
tion of the ylide generated from intermediate 4 and
aldehyde 5. The intermediate 4 could be prepared from the
chiral epoxide obtained from resolution of the racemic ep-
oxide 6.
The other key fragment, aldehyde 5, was prepared from L-
(+)-diethyltartaric acid according to a known procedure.10
The Wittig salt 15 was treated with n-butyllithium and re-
acted with aldehyde 5 to afford 16a, which was then hy-
drogenated to yield the saturated alcohol 17 (Scheme 3).
Swern oxidation of 17 gave the aldehyde 18 which was
subjected to a modified Wadsworth–Emmons reaction, in
the presence of sodium hydride in tetrahydrofuran, to pro-
vide the intermediate 3 exclusively.
The synthesis of intermediate 4 started with commercially
available 5-hexen-1-ol (Scheme 1). Accordingly, 5-hex-
en-1-ol was protected as its benzyl ether 7 with sodium
hydride and benzyl bromide, then epoxidized with m-
chloroperoxybenzoic acid (MCPBA) to give the racemic
oxirane 6. The oxirane 6 was hydrolyzed employing (S,S)-
Salen-Co-(OAc) catalyst6 to give the chiral epoxide 8.
The epoxide was reduced with lithium aluminum hydride
to generate the secondary alcohol 9, which was then pro-
tected as its tert-butyldiphenylsilyl ether 10. Debenzyla-
tion of 10 with carbon-supported palladium afforded
The intermediate 3 upon one-pot desilylation, deaceton-
ization and lactonization using 3% HCl in methanol af-
forded iso-cladospolide B [a]D = –106.0 (c 1.35, MeOH)
{lit.4b [a]D = –105.0 (c 0.23, MeOH)}.11
The intermediate 3, on hydrolysis with lithium hydroxide,
was converted into acid 19 which has already been uti-
lized for the synthesis of cladospolide B (Scheme 4).4a
SYNTHESIS 2006, No. 23, pp 4041–4045
x
x.
x
x
.
2
0
0
6
Advanced online publication: 12.10.2006
DOI: 10.1055/s-2006-950317; Art ID: Z15106SS
© Georg Thieme Verlag Stuttgart · New York

4042
P. Srihari et al.
PAPER
NaH, BnBr
THF, 3 h, 0 °C–r.t.
MCPBA
CH2Cl2, 2 h
Jacobsen resoln
45%, 98% ee
O
O
OBn
OBn
OBn
OH
8
7
6
96%
84%
TBDPSCI, imidazole
CH2Cl2, 4 h, 0 °C–r.t.
I2, TPP, imidazole
benzene, 1 h
Pd/C, EtOAc
12 h
LAH, THF
30 min
OH
OTBDPS
OTBDPS
OBn
OBn
OH
96%
94%
96%
92%
9
10
11
OTBDPS
OTBDPS
TPP, benzene
reflux,16 h
+PPh3I–
I
90%
15
14
Scheme 1
MBT, TPP
DEAD
MCPBA
CH2Cl2
OTBDPS
O
S
OTBDPS
N
N
S
11
OTBDPS
O
LiOH, MeOH–H2O
80%
TBDPS deprotection
COOH
S
3
S
12
3
3
O
13
O
19
O
OHC
OBn
OTBDPS
O
O
O
OH
O
O
LiHMDS or
NaHMDS or
n-BuLi or
LDA
OBn
OH
1) lactonization
OH
O
16
2) acetonide
deprotection
O
O
OH
cladospolide B
Scheme 2
Scheme 4
O
O
In conclusion, we have developed a simple and efficient
route for total synthesis of iso-cladospolide B, and synthe-
sized a common intermediate that can be further used for
the total synthesis of cladospolide B. Furthermore, by al-
tering Jacobsen’s salen reagent, the other isomer can also
be easily prepared. Further applications of this class of
compounds for analogue synthesis is underway and will
be published in future.
OHC
OBn
5
O
OTBDPS
n-BuLi, THF, 2 h
+PPh3I–
OBn
68%
O
OTBDPS
15
16a
DMSO, (COCl)2,
Et3N, CH2Cl2
–78 °C
OTBDPS
O
Pd/C, H2 atm
92%
OH
90%
O
17
Column chromatography was performed using silica gel 60–120
mesh. All solvents were dried and distilled prior to use. IR spectra
were recorded on a Perkin-Elmer Infrared spectrophotometer as
KBr wafers, neat or in CHCl3, as a thin film. 1H and 13C NMR were
recorded on a Varian Gemini 200, Bruker Avance 300 or Varian
Unity 400 instrument (1H operating frequencies of 300 MHz and
400 MHz, respectively) using TMS as an internal standard. Mass
spectra were recorded on Micro mass VG 7070H mass spectrometer
for EI, VG Autospec mass spectrometer for FABMS and micromass
Quatro LC triple quadrupole mass spectrometer for ESI analysis.
The optical rotations were recorded on a JASCO DIP-360 digital
polarimeter at 25 °C. Enantiomeric excess was analyzed using a
chiralcel OB (H) 250 × 4.6 mm Daicel column; flow rate 1.0 mL/
min; mobile phase 10% IPA in n-hexane; Machine Shimadzu LC 10
AT pump, and SPD-10A UV detection at 254 nm.
MeO2CCH2P(O)(OCH2CF3)2
NaH, THF, 0 °C to –78 °C
OTBDPS
18
O
CHO
O
85%
OTBDPS
O
3% HCl in MeOH
COOMe
75%
O
3
OH
OH
O
iso-cladospolide B
O
[(Hex-5-enyloxy)methyl] Benzene (7)
To a well-stirred suspension of freshly activated NaH (2.88 g, 120
mmol, 60% w/v dispersion in mineral oil) in anhydrous THF (50
mL), a solution of 5-hexen-1-ol (10 g, 100 mmol) in dry THF (60
mL) was added dropwise at 0 °C. After 30 min, benzyl bromide
(20.52 g, 120 mmol) was added and the reaction mixture was
brought to r.t. and stirred for 3 h. The reaction was quenched with
Scheme 3
Synthesis 2006, No. 23, 4041–4045 © Thieme Stuttgart · New York

PAPER
Stereoselective Total Synthesis of iso-Cladospolide B
4043
ice pieces and product was extracted with Et2O (3 × 100 mL). The
combined organic layer was washed with H2O (100 mL), brine
(2 × 50 mL) and dried over anhydrous Na2SO4. After filtering and
removing the volatiles under reduced pressure, the crude benzyl
ether was purified by column chromatography (EtOAc–hexane,
5%) to afford the pure product 7.
1H NMR (300 MHz, CDCl3): d = 7.34–7.20 (m, 5 H), 4.46 (s, 2 H),
3.82–3.70 (m, 1 H), 3.44 (t, J = 6.0 Hz, 2 H), 1.68–1.30 (m, 6 H),
1.16 (d, J = 6.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 138.6, 128.3, 127.6, 127.5, 72.8,
70.3, 67.8, 39.0, 29.6, 23.4, 22.4.
ESI-MS: m/z calcd for C12H20O2 + H: 209.30; found: 209.
Yield: 18.3 g (96%); colorless liquid.
IR (neat): 3069, 3031, 1639.7, 1495.4, 1453.8, 1361.9 1204.6,
1027.5, 994.8, 910.4, 735.8, 697.6, 612.5 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.34–7.20 (m, 5 H), 5.83–5.71 (m,
1 H), 5.0–4.87 (m, 2 H), 4.47 (s, 2 H), 3.43 (t, J = 6.2 Hz, 2 H), 2.06
(q, J = 7.2 Hz, 2 H), 1.67–1.55 (m, 2 H), 1.54–1.41 (m, 2 H).
13C NMR (50 MHz, CDCl3): d = 138.5, 128.1, 127.4, 127.3, 72.7,
69.9, 51.9, 46.7, 32.0, 29.3, 22.5.
(R)-[6-(Benzyloxy)hexan-2-yloxy]-tert-butyldiphenylsilane (10)
To a stirred solution of alcohol 9 (3.80 g, 18.18 mmol) in dry
CH2Cl2 (50 mL) and imidazole (1.85 g, 27.27 mmol) at 0 °C was
added TBDPSCl (5.99 g, 21.81 mmol), dropwise and the reaction
was stirred at r.t. for 4 h. The reaction mixture was quenched with
H2O (50 mL) and extracted with CH2Cl2 (3 × 40 mL). The com-
bined organic layer was washed with brine (2 × 40 mL) and dried
over anhydrous Na2SO4. The solvent was concentrated under re-
duced pressure and the residue was purified by column chromatog-
raphy (EtOAc–hexane, 10%) to give 10.
ESI-MS: m/z calcd for C13H18O + H: 191; found: 191.
Yield: 7.5 g (92%); colorless liquid; [a]D20 +11.74 (c, 2.1, CHCl3).
2-[4-(Benzyloxy)butyl]oxirane (6)
To a solution of olefin 7 (18.0 g, 94.0 mmol) dissolved in dry
CH2Cl2 (150 mL) was added NaHCO3 (23.78 g, 282 mmol), fol-
lowed by MCPBA (24.39 g, 141.36 mmol) and stirred at r.t. for 2 h.
The reaction mixture was diluted with H2O (150 mL) and extracted
with CH2Cl2 (3 × 100 mL). The combined organic layer was
washed with brine (2 × 100 mL) and dried over anhydrous Na2SO4.
The solvent was removed under reduced pressure and the crude
product was purified by column chromatography (EtOAc–hexane,
20%) to afford product 6 (16.38 g, 84%) as a colorless oil.
IR (neat): 2930.7, 1618, 1354.8, 1219.2, 1109.6, 772.4, 701.0, 612.2
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.67–7.60 (m, 4 H), 7.41–7.19 (m,
11 H), 4.42 (s, 2 H), 3.87–3.74 (m, 1 H), 3.34 (t, J = 6.0 Hz, 2 H),
1.54–1.22 (m, 6 H), 1.07–1.09 (m, 12 H).
13C NMR (75 MHz, CDCl3): d = 135.8, 129.3, 128.2, 127.3, 72.7,
70.3, 69.5, 39.2, 29.7, 27.0, 23.1, 21.8, 19.2.
FAB-MS: m/z calcd for C29H38O2Si + H: 447.7; found: 448.
(S)-2-[4-(Benzyloxy)butyl]oxirane (8)
(R)-5-(tert-Butyldiphenylsilyloxy)hexan-1-ol (11)
A solution of benzyl compound 10 (7.0 g, 15.6 mmol) in EtOAc (45
mL) was mixed with Pd/C (10% mol) and stirred for 12 h under 55
psi hydrogen atmosphere. The catalyst was removed by filtration
and the solvent was evaporated to give a residue that was purified
by column chromatography (EtOAc–hexane, 35%) to afford the
pure 11.
A mixture of (S,S)-(–)-N,N¢-bis(3,5-di-tert-butylsalicylidene)-1,2-
cyclohexanediaminocobalt (143.0 mg, 0.24 mmol), toluene (1 mL)
and AcOH (0.027 mL, 0.006 mmol) was stirred while open to the
air for 1 h at r.t. The solvent was removed by rotary evaporator un-
der reduced pressure and the brown residue was dried under high
vacuum. The oxirane 6 (16.38 g, 79.5 mmol) was added in one por-
tion, and the mixture was cooled in an ice–water bath. H2O (0.78
mL, 43.7 mmol) was slowly added over 1 h, whilst keeping the tem-
perature of the reaction mixture below 20 °C. The ice bath was re-
moved and the reaction was stirred for 24 h at r.t.. The product 8 was
isolated by column chromatography (EtOAc–hexane, 20%).
20
Yield: 5.37 g (96%); light yellow viscous oil; [a]D +8.25 (c 1.1,
CHCl3).
IR (neat): 3417.3, 2930.1, 1618.3, 1354.1, 1219.0, 1109, 772.1,
702.5, 612.1 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.67–7.61 (m, 4 H), 7.41–7.22 (m,
6 H), 3.89–3.75 (m, 1 H), 3.49 (d, J = 6.2 Hz, 2 H), 1.51–1.22 (m,
6 H), 1.08–1.01 (m, 12 H).
13C NMR (75 MHz, CDCl3): d = 129.5, 128.5, 127.4, 126.7, 79.3,
53.0, 52.3, 49.6, 38.5, 37.7, 28.37.
20
Yield: 7.4 g (45%); colorless liquid; [a]D –5.12 (c 2.3, CHCl3);
99% ee.
IR (neat): 2934, 2847.7, 1637.6, 1355.5, 1218.8, 1102.5, 771.9
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.33–7.19 (m, 5 H), 4.46 (s, 2 H),
3.44 (t, 6.0 Hz, 2 H), 2.87–2.79 (m, 1 H), 2.67 (dd, J = 3.8, 9.1 Hz,
1 H), 2.39 (dd, J = 2.2, 7.5 Hz, 1 H), 1.71–1.48 (m, 6 H).
FAB-MS: m/z calcd for C22H32O2Si + H: 356.59; found: 357.
13C NMR (75 MHz, CDCl3): d = 138.5, 128.1, 127.4, 127.3, 72.7,
69.9, 51.9, 46.7, 32.1, 29.4, 22.5.
(R)-tert-Butyl(6-iodohexan-2-yloxy)diphenylsilane (14)
To a solution of alcohol 13 (5.0 g, 14.04 mmol) in dry benzene (50
mL) was added imidazole (1.91 g, 28.28 mmol), TPP (4.95 g, 18.9
mmol) and iodine (7.13 g, 28.08 mmol) at 0 °C. After 5 min, the
cooling bath was removed and the reaction mixture was stirred for
1 h at r.t., during which time the color changed from brown to bright
yellow and the mixture became highly viscous. The reaction was
quenched with sat. aq Na2S2O3 (30 mL) and extracted with Et2O
(3 × 60 mL). The combined organic layer was washed with sat.
Na2S2O3 solution (40 mL), brine (2 × 40 mL) and dried over anhy-
drous Na2SO4. The solvent was removed on a rotavapor and the
crude product was purified by flash chromatography (EtOAc–hex-
ane, 5%) to give the iodo compond 14 (6.34 g, 96%) as a light yel-
low oil. This was refluxed with triphenylphosphine (1 equiv) in
benzene for 16 h then the solvent was filtered off and the solid res-
idue was washed with petroleum ether. The resulting salt 15 was
used without further purification.
ESI-MS: m/z calcd for C13H18O2 + H: 207.3; found: 207.
(R)-6-(Benzyloxy)hexan-2-ol (9)
To a well stirred suspension of LiAlH4 (930 mg, 26.57 mmol) in dry
THF (15 mL), a solution of epoxide 8 (5.0 g, 24.15 mmol) in THF
(30 mL) was added dropwise at 0 °C. The reaction mixture was
brought to r.t. and stirred for 30 min. The reaction mixture was
quenched with sat aq NH4Cl (10 mL) at 0 °C. The reaction mixture
was filtered and dried over anhydrous Na2SO4, filtered and concen-
trated. Purification by column chromatography (EtOAc–hexane,
20%) gave the product 9.
Yield: 4.08 g (94%); colorless oil; [a]D20 +9.5 (c 1.8, CHCl3).
IR (neat): 3417.0, 2931.2, 2847.7, 1618., 1354.0, 1219.0, 1108.0,
772.2, 702.0, 612.0 cm–1.
Synthesis 2006, No. 23, 4041–4045 © Thieme Stuttgart · New York

4044
P. Srihari et al.
PAPER
{(R)-(Z)-7-[(4S,5S)-5-(Benzyloxymethyl)-2,2-dimethyl-1,3-diox-
olan-4-yl]hept-6-en-2-yloxy}-9-tert-butyldiphenylsilane (16a)
A suspension of salt 15 (7.36 g 12.7 mmol) in dry THF (60 mL) was
treated with n-BuLi (1.6 M solution in hexane, 7.28 mL, 12.76
mmol) at 0 °C and stirred at r.t. for 1 h. The aldehyde 5 (2.65 g, 10.6
mmol) in THF (30 mL) was added at 0 °C and, after 2 h, the reaction
mixture was quenched with sat aq NH4Cl (5 mL) and extracted with
EtOAc (3 × 60 mL). The combined organic layer was washed with
brine (2 × 30 mL) and dried over anhydrous NaSO4. Volatiles were
removed under reduced pressure and the crude product was purified
by column chromatography (EtOAc–hexane, 35%) to furnish the
product 16a.
dropwise at –78 °C. After 30 min, the reaction mixture was diluted
with H2O (30 mL) and extracted with EtOAc (3 × 30 mL). The com-
bined organic layer was washed with H2O (2 × 30 mL), brine
(2 × 30 mL) and dried over anhydrous Na2SO4. Solvent was re-
moved and the residue was chromatographed (EtOAc–hexane,
50%) to furnish the product 3.
Yield: 2.53 g (84.5%); clear, colorless liquid; [a]D20 +35.18 (c 1.5,
CHCl3).
IR (neat): 3416.2, 2932.5, 1729.0, 1618.2, 1376.1, 1243.1, 1049.8,
912.8, 794.7, 612.1 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.72–7.56 (m, 4 H), 7.43–7.26 (m,
6 H), 6.11 (dd, J = 11.7, 8.6 Hz, 1 H), 5.89 (d, J = 12.5 Hz, 1 H),
5.20 (t, J = 8.6 Hz, 1 H), 3.88–3.73 (m, 1 H), 3.70 (s, 3 H), 3.67–
3.55 (m, 1 H), 1.63–1.11 (m, 16 H), 1.08–0.98 (m,12 H).
13C NMR (50 MHz, CDCl3): d = 165.7, 135.8, 134.6, 129.3, 127.3,
122.5, 109.2, 81.0, 76.1, 69.5, 51.4, 39.4, 31.9, 29.6, 27.3, 27.0,
25.9, 25.0, 23.1, 19.2.
Yield: 4.95 g (68%); colorless oil; [a]D20 +15.1 (c 1.3, CHCl3).
IR (neat): 2932.7, 1374.1, 1219.0, 1106.9, 771.5, 702.1, 610.7,
509.3 cm–1.
1H NMR (200 MHz): d = 7.67–7.60 (m, 4 H), 7.41–7.16 (m, 11 H),
5.57–5.46 (m, 1 H), 5.32 (t, J = 9.5 Hz, 1 H), 4.58–4.46 (m, 2 H),
3.82–3.71 (m, 2 H), 3.55–3.41 (m, 2 H), 2.10–1.79 (m, 2 H), 1.39
(m, 6 H), 1.38–1.23 (m, 4 H), 1.07–0.99 (m, 12 H).
FAB-MS: m/z calcd for C32H46O5Si + H: 539.77; found: 540.
13C NMR (75 MHz, CDCl3): d = 135.9, 135.8, 129.4, 129.3, 128.2,
127.5, 127.4, 127.3, 109.3, 80.5, 73.5, 69.3, 38.8, 27.6, 27.1, 27.0,
24.0, 23.1, 19.2.
(Z)-3-{(4S,5S)-5-[(R)-6-(tert-Butyldiphenylsilyloxy)heptyl]-2,2-
dimethyl[1,3]dioxolan-4-yl}acrylic Acid (19)
To the ester 3 (2.3 g, 4.27 mmol) dissolved in MeOH (15 mL) and
H2O (10 mL) was added LiOH·H2O (0.51 g, 21.3 mmol) and stirred
at r.t. for 24 h. The reaction mixture was further diluted with H2O
(10 mL) and stirred for 30 min then concentrated by rotary evapo-
rator to quarter of its volume. The mixture was acidified with 1 M
HCl (pH 3) and the reaction mixture was extracted with EtOAc
(3 × 30 mL). The combined organic layer was washed with brine
(2 × 30 mL) and dried over anhydrous Na2SO4, filtered, evaporated
and the crude product was purified by column chromatography
(EtOAc–hexane, 80%) to yield pure 19.
FAB-MS: m/z calcd for C36H48O4Si + H: 572.87; found: 573.
(4S,5S)-5-[(R)-6-(tert-Butyldiphenylsilyloxy)heptyl]-2,2-di-
methyl-1,3-dioxolan-4-yl}methanol (17)
A solution of benzyl compound 16a (4.5 g, 7.86 mmol) in EtOAc
(40 mL) was mixed with Pd/C (10 mol%) and stirred for 24 h at r.t
under H2 atmosphere. The catalyst was removed by filtration
through a celite pad and the solvent was evaporated. The residue
was purified by column chromatography (EtOAc–hexane, 35%) to
give 17.
20
Yield: 2.04 g (91%); colorless liquid; [a]D +40.14 (c 1.12,
Yield: 3.49 g (92%); colorless liquid.
CHCl3).
IR (neat): 3451.4, 1637.3, 1352.9, 1219.6, 1109.9, 772.5 cm–1.
IR (neat): 3416.6, 1771.0, 1618.1, 1380.4, 1245.8, 1054.4, 913.4,
795.0, 744.1, 613.3 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.69–7.58 (m, 4 H), 7.39–7.24 (m,
6 H), 6.22 (dd, J = 11.7, 8.6 Hz, 1 H), 5.89 (d, J = 11.7 Hz, 1 H),
5.17 (t, J = 8.6 Hz, 1 H), 3.86–3.73 (m, 1 H), 3.70–3.55(m, 1 H),
1.61–1.10 (m, 16 H), 1.09–0.96 (m, 12 H).
13C NMR (75 MHz, CDCl3): d = 169.9, 148.1, 135.8, 129.4, 129.3,
127.4, 127.3, 122.1, 109.4, 81.0, 76.1, 69.1, 39.3, 31.8, 29.6, 27.3,
27.0, 25.8, 25.1, 23.1, 19.2, 14.1.
1H NMR (300 MHz, CDCl3): d = 7.67–7.60 (m, 4 H), 7.42–7.28 (m,
6 H), 3.86–3.68 (m, 3 H), 3.67–3.58 (m, 1 H), 3.56–3.45 (m, 1 H),
1.56 (br s, 1 H), 1.56–1.13 (m, 16 H), 1.07–1.01 (m, 12 H).
13C NMR (100 MHz, CDCl3): d = 135.8, 134.8, 134.5, 129.36,
129.31, 127.38, 127.31, 108.5, 81.4, 76.8, 69.4, 61.9, 39.2, 32.9,
29.6, 27.3, 26.9, 25.9, 25.0, 23.2, 19.2.
FAB-MS: m/z calcd for C29H44O4Si + H: 485.76; found 486.
(4R,5S)-5-[(R)-6-(tert-Butyldiphenyloxy)heptyl)-2,2-dimethyl-
1,3-dioxolane-4-carbaldehyde (18)
FAB-MS: m/z calcd for C31H44O5Si + H: 525.78; found: 526.
To the solution of oxalylchloride (1.68 g, 1.16 mL) in dry CH2Cl2
(20 mL) at –78 °C, was added DMSO (2.06 g, 1.88 mL) slowly via
syringe and the reaction was stirred for 10 min. The alcohol 17 (3.2
g, 6.6 mmol) in dry CH2Cl2 (25 mL) was then added dropwise at
–78 °C. After 2 h, Et3N (5.5 mL, 39.6 mmol) was added slowly and
the reaction mixture was allowed to come to 0 °C over 30 min. The
reaction mixture was diluted with H2O (50 mL) and extracted with
CH2Cl2 (3 × 30 mL). The combined organic layer was washed with
brine (2 × 30 mL) and dried over anhydrous Na2SO4. Evaporation
of the solvent gave the crude aldehyde 18 (3.0 g) which was used
directly for the next step.
Acknowledgment
Two of us (E.V.B.) and (S.J.H.) thank CSIR, New Delhi for finan-
cial assistance.
References
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Synthesis 2006, No. 23, 4041–4045 © Thieme Stuttgart · New York

PAPER
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Synthesis 2006, No. 23, 4041–4045 © Thieme Stuttgart · New York