An efficient convergent access to spiroketal segment of (+)-spiroxaline methyl ether

Article abstract of DOI:10.1055/s-0030-1258456

Starting from trimethylsilylacetylene, a facile synthesis of optically pure spiroketal unit of (+)-spiroxaline methyl ether has been described. The synthesis entails stepwise alkylation and acylation of an alkyne with two different readily available chira

Full text of DOI:10.1055/s-0030-1258456

PAPER
1137
An Efficient Convergent Access to Spiroketal Segment of (+)-Spiroxaline
Methyl Ether
S
piroketal Segment of
a
(+)-Spiroxa
n
line Methyl
dEther eep Singh, Narshinha P. Argade*
Division of Organic Chemistry, National Chemical Laboratory (CSIR), Pune 411008, India
Fax +91(20)25902629; E-mail: np.argade@ncl.res.in
Received 15 December 2010; revised 18 January 2011
Complementary to Trost and Weiss alkyne strategy,6c our
synthesis of important spiroketal system in compound 1b
also began with TMS-protected acetylene. Regioselective
ring opening of an enantiomerically pure (R)-oxirane 2
Abstract: Starting from trimethylsilylacetylene, a facile synthesis
of optically pure spiroketal unit of (+)-spiroxaline methyl ether has
been described. The synthesis entails stepwise alkylation and acyla-
tion of an alkyne with two different readily available chiral building
blocks followed by the reductive in situ regio- and stereoselective (~100% ee)9 with the trimethylsilylacetylene carbanion
spiroketalization pathway.
exclusively provided the required alkynol 3 in 89% yield
(Scheme 1). Chemoselective O-benzyl protection of the
formed secondary alcohol 3 directly furnished the in situ
desilylated required acetylene derivative 4 in 77% yield.
Condensation of the acetylenic carbanion of 4 with the
enantiomerically pure TBDPS-protected aldehyde 510
yielded the chromatographically inseparable diastereo-
meric mixture of 7 (~1:1, by NMR spectroscopy) in 72%
yield. TEMPO-oxidation of obtained secondary alcohol 7
supplied the required alkynone 9 in 85% yield. Unfortu-
nately, all our attempts for the TBAF-induced deprotec-
tion of TBDPS group in compound 9 failed and we always
ended up with the formation of decomposed materials.
Assuming that the alkyne unit in compound 9 is not stable
to our TBDPS-deprotection conditions, the chemoselec-
tive C≡C bond reduction in the alkyne 9 was attempted
under very mild catalytic hydrogenation conditions, and
fortunately it provided the desired single product 11 in
~100% yield. Our speculation about the triple bond deli-
cacy was true and the TBDPS group deprotection in the
corresponding reduction product 11 made available the
stable compound 12 in 92% yield. The compound 12 on
catalytic hydrogenolysis of two O-benzyl groups under-
went regio- and stereoselective concomitant spiroketal-
ization to furnish the essential product (+)-13 in 85%
yield. At this stage we could sense that it would be feasi-
ble to curtail down the two steps in the above mentioned
synthesis progression by avoiding the TBDPS protection.
Thus, the reaction of an alkyne carbanion of 4 was per-
formed with the enantiomerically pure benzyl-protected
aldehyde 611 yielding the column inseparable diastereo-
meric mixture 8 (2:3, by NMR spectroscopy) in 75%
yield. The obtained product 8 on TEMPO oxidation
(84%), followed by simultaneous catalytic hydrogenation
of triple bond and hydrogenolysis of three O-benzyl
groups again directly furnished the diastereomerically
pure compound (+)-13 in 82% yield (Scheme 1).
Key words: alkyne, (R)-oxirane, (R)-g-valerolactone, nucleophilic
reactions, (+)-spiroketal segment synthesis
The spirolaxines have been isolated from various strains
of white rot fungi genera Sporotrichum and Phanerocha-
etei and the stereochemical structural assignment has been
done on the basis of single-crystal X-ray analysis data.1,2
They exhibit various biological activities such as choles-
terol lowering, cytotoxic towards endothelial cells
(BMEC and Huvec), and variety of tumor cell lines (LoVo
and HL60).3,4 More specifically, they possess prominent
and highly selective activity against the gastric and duode-
nal ulcers inducing microaerophilic Gram-negative bacte-
rium Helicobacter pylori.5 Retrosynthetically, (+)-
spiroxaline methyl ether (1b) is a remotely latent trifun-
tionalized 3-alkyl-substituted 5,7-dimethoxyphthalide
(Figure 1). Attractive syntheses of target compound have
been recently reported by employing the Diels–Alder re-
action, Julia olefination, Prins cyclization, cyclopropanol-
based, and an alkyne-based strategies.6 Large number of
bioactive complex natural products contain the spiroketal
motifs and synthesis of enantiomerically pure spiro-
skeletons is an exigent task of current interest.7 In contin-
uance with our studies on synthesis of anti-Helicobacter
pylori agents,8 we herein report the practical synthesis of
a crucial spiroketal part of the (+)-spiroxaline methyl
ether (1b) by means of alkylation-acylation of an alkyne
unit (Schemes 1 and 2).
O
OMe
O
O
O
RO
1a R = H, spiroxaline
1b R = Me, spiroxaline methyl ether
Finally, we deliberated for the acylation of alkyne 4 with
the appropriate chiral lactone to avoid the involved sec-
ondary alcohol to ketone TEMPO-oxidation step in
Scheme 1 to formulate the still one step shorter execution
of spiroketal 13 synthesis (Scheme 2). Indeed the reaction
of an acetylenic carbanion of 4 with commercially avail-
Figure 1 Helicobacter pylori antibiotics
SYNTHESIS 2011, No. 7, pp 1137–1141
x
x
.
x
x
.2
0
1
1
Advanced online publication: 02.03.2011
DOI: 10.1055/s-0030-1258456; Art ID: Z53710SS
© Georg Thieme Verlag Stuttgart · New York

1138
M. Singh, N. P. Argade
PAPER
O
SiMe3
OBn
H
n-BuLi,
OH
H
SiMe3
NaH, BnBr, DMF, 4 h
(77%)
BnO
BF3•OEt2, THF, –78 °C, 1 h
BnO
BnO
(89%)
4
2
3
OH
O
TEMPO, PhI(OAc)2
CH2Cl2, 45 min
OBn
OBn
for 9 (R = TBDPS)
n-BuLi, THF, –78 °C, 1 h
O
H2, Pd/C, EtOAc
1 h (100%)
BnO
OR
BnO
OR
9 R = TBDPS 85%
10 R = Bn 84%
7 R = TBDPS 72%
8 R = Bn 75%
H
OR
for 10 (R = Bn)
5 R = TBDPS
6 R = Bn
H2, Pd/C, MeOH
60 psi, 8 h (82%)
O
OBn
O
OBn
O
TBAF, THF
H2, Pd/C, MeOH
60 psi, 8 h (85%)
BnO
BnO
O
6 h (92%)
OTBDPS
OH
HO
11
12
13
Scheme 1 Syntheses of (+)-spiroketal segment via two partially separate routes
able enantiomerically pure (R)-g-valerolactone provided nal product, the (+)-spiroxaline methyl ether (1b) with
the stable alkynonol 14 in 82% yield via the nucleophilic 79% yield have been well established in the literature.6e
lactone ring opening. Alkynonol 14 under the catalytic
In summary, we have demonstrated a concise and effi-
hydrogenation conditions, once again directly furnished
cient formal synthesis of the enantiomerically and diaste-
the diastereomerically pure compound (+)-13 in 87%
reomerically pure bioactive natural product (+)-
spiroxaline methyl ether by using readily available appro-
priate chiral building blocks, utilizing the most promising
yield. Thus, starting from oxirane 2, the desired (+)-
spiroketal 13 was obtained in just four steps in 49% over-
all yield, and the obtained analytical and spectral data for
alkynes reactivity paradigm. In the present four-step ap-
(+)-13 were in complete agreement with the reported da-
proach from the oxirane 2 to spiroketal 13, variety of de-
ta.1,2,6 The quantitative NBS-induced conversion of spiro-
sired bond forming and bond breaking processes take
place under the set of our applied four reaction conditions
and hence represents a nice illustration of bond-forming
bond-cleaving economy.
alcohol 13 to spiro-bromide 15 and its alkyl–alkyl Suzuki
coupling with the enantiomerically pure (R)-3-allyl-5,7-
dimethoxyisobenzofuran-1(3H)-one6g that delivers the fi-
O
The 1H NMR spectra were recorded on 200 MHz NMR spectrome-
ter, 400 MHz NMR spectrometer, and 500 MHz NMR spectrometer
using TMS as an internal standard. The 13C NMR spectra were re-
corded on 200 NMR spectrometer (50 MHz), 400 NMR spectrom-
eter (100 MHz), and 500 NMR spectrometer (125 MHz). Mass
spectra were taken on MS-TOF mass spectrometer. The IR spectra
were recorded on an FT-IR spectrometer. Elemental analyses were
done at NCL, Pune. HRMS (ESI) were recorded on the mass spec-
trometer at IICT, Hyderabad. Column chromatographic separations
were carried out on silica gel (60–120 mesh). Commercially avail-
able trimethylsilylacetylene, n-butyllithium, BF3·OEt2, TEMPO,
iodobis(acetoxy)benzene, Pd/C (10 wt%), tetrabutylammonium
fluoride, sodium hydride, benzyl bromide, and (R)-g-valerolactone
were used. Petroleum ether (PE) used refers to the fraction boiling
in the range 60–80 °C.
H
O
OBn
OBn
OBn
n-BuLi, BF3•OEt2
THF, –78 °C
OH
O
, 1 h (82%)
OBn
4
14
H2, Pd/C, MeOH
60 psi, 8 h (87%)
OMe
O
O
O
O
MeO
R
Fu's alkyl–alkyl
Suzuki coupling6e
13 R = OH
15 R = Br
ref. 6e
(R)-2-[2-(Benzyloxy)ethyl]oxirane (2)
25
Prepared according to the known procedure;9 [a]D +16.2 (c 2.0
CHCl3).
OMe
O
O
IR (neat): 1601 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.65–2.03 (m, 2 H), 2.52 (dd,
J = 6, 2 Hz, 1 H), 2.77 (t, J = 4 Hz, 1 H), 3.00–3.11 (m, 1 H), 3.62
(t, J = 4 Hz, 2 H), 4.52 (s, 2 H), 7.20–7.40 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 32.8, 46.9, 49.9, 66.9, 72.9, 127.4
(2 C), 128.2, 138.1.
O
O
MeO
(+)-spiroxaline methyl ether (1b)
Scheme 2 Concise and efficient formal synthesis of (+)-spiroxaline
methyl ether
ESIMS: m/z = 201 [M + Na]+.
Synthesis 2011, No. 7, 1137–1141 © Thieme Stuttgart · New York

PAPER
Spiroketal Segment of (+)-Spiroxaline Methyl Ether
1139
(S)-1-(Benzyloxy)-6-(trimethylsilyl)hex-5-yn-3-ol (3)
4.22–4.33 (m, 1 H), 4.40–4.51 (m, 3 H), 4.59–4.66 (m, 1 H), 7.20–
7.45 (m, 16 H), 7.65–7.72 (m, 4 H).
To a stirred solution of trimethylsilylacetylene (7.14 mL, 50.56
mmol) in THF (60 mL) at –78 °C was added n-BuLi (1.60 M in hex-
ane, 30.54 mL, 48.87 mmol) and the reaction mixture was stirred for
30 min. To the above mixture was added dropwise BF3⋅OEt2 (6.44
mL, 52.24 mmol) at –78 °C, the stirring continued for 10 min, and
then the epoxide 2 (3.00 g, 16.85 mmol) in THF (10 mL) was added
dropwise to the above mixture. The mixture was stirred further for
1 h at –78 °C and quenched with sat. aq NH4Cl (5 mL). The mixture
was concentrated in vacuo and the obtained residue was dissolved
in EtOAc (60 mL). The organic layer was washed with H2O (15
mL), brine (15 mL), and dried (Na2SO4). Removal of the solvent in
vacuo followed by silica gel column chromatography of the result-
ing residue using EtOAc–PE (8:92) as eluent afforded pure product
3 as a colorless oil;12 yield: 4.13 g (89%); [a]D25 +3.4 (c 1.0 CHCl3).
13C NMR (100 MHz, CDCl3): d = 19.2, 22.8, 22.9, 24.3, 27.0, 33.3,
33.5, 34.4, 34.5, 34.8, 62.5, 62.7, 66.5, 69.09, 69.13, 71.6, 72.9,
74.47, 74.50, 81.6, 81.7, 83.10, 83.13, 127.4, 127.52, 127.54, 127.6,
127.7, 127.8, 128.3, 129.45, 129.54, 134.1, 134.2, 134.6, 135.9,
138.4.
ESIMS: m/z = 657 [M + Na]+.
Anal. Calcd for C41H50O4Si: C, 77.56; H, 7.94. Found: C, 77.27; H,
8.36.
(2R,9S)-2,9,11-Tris(benzyloxy)undec-6-yn-5-ol (8)
Similarly, starting from compound 4 (918 mg, 3.12 mmol) and us-
ing the benzyl-protected 6 (500 mg, 2.60 mmol), product 8 was ob-
tained as a colorless oil, following the above procedure; yield: 949
mg (75%); [a]D25 +23.1 (c 0.5 CHCl3).
IR (neat): 3444, 2176 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.15 (s, 9 H), 1.70–2.00 (m, 2 H),
2.44 (dd, J = 8, 2 Hz, 2 H), 3.07 (br s, 1 H), 3.57–3.80 (m, 2 H),
3.87–4.04 (m, 1 H), 4.52 (s, 2 H), 7.20–7.40 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 0.02, 28.5, 35.3, 68.5, 69.3, 73.2,
87.0, 103.3, 127.6, 127.7, 128.4, 137.8.
IR (CHCl3): 3433, 2252 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.21 (d, J = 6 Hz, 3 H), 1.55–2.10
(m, 6 H), 2.51 (d, J = 6 Hz, 2 H), 2.62 (br s, 1 H), 3.40–3.65 (m, 3
H), 3.65–3.85 (m, 1 H), 4.30–4.55 (m, 6 H), 4.64 (d, J = 12 Hz, 1
H), 7.20–7.40 (m, 15 H).
13C NMR (50 MHz, CDCl3): d = 19.3, 19.5, 24.3, 31.9, 32.1, 33.7,
33.9, 34.4, 62.4, 66.5, 70.2, 71.6, 72.9, 74.4, 74.5, 81.6, 83.1,
127.45, 127.53, 127.6, 127.7, 127.8, 128.3, 138.3, 138.6.
ESIMS: m/z = 277 [M + H]+, 299 [M + Na]+, 315 [M + K]+.
1-{[(S)-1-(Benzyloxy)hex-5-yn-3-yloxy]methyl}benzene (4)
To a stirred suspension of NaH (60% dispersion in mineral oil, 1.33
g, 27.89 mmol) in DMF (40 mL) was added alcohol 3 (3.50 g, 12.68
mmol) in DMF (15 mL) at 0 °C. At the end of 45 min, benzyl bro-
mide (1.50 mL, 27.89 mmol) was added to the reaction mixture and
further stirred at 25 °C for 4 h. The mixture was quenched with sat.
aq NH4Cl (5 mL) and extracted with EtOAc (100 mL). The organic
layer was washed with brine (25 mL) and dried (Na2SO4). Removal
of the solvent in vacuo followed by silica gel column chromatogra-
phy of the resulting residue using EtOAc–PE (5:95) as eluent af-
forded the pure product 4 as a colorless oil;13 yield: 2.87 g (77%);
[a]D25 +43.2 (c 1.7 CHCl3).
ESIMS: m/z = 504 [M + NH4]+, 509 [M + Na]+, 525 [M + K]+.
HRMS (ESI): m/z calcd for C32H38O4 + Na [M + Na]+: 509.2667;
found: 509.2648.
(2R,9S)-9,11-Bis(benzyloxy)-2-[(tert-butyldiphenylsilyl)oxy]un-
dec-6-yn-5-one (9)
To a stirred solution of alcohol 7 (1.00 g, 1.57 mmol) in CH2Cl2
(1.50 mL) at r.t. was added TEMPO (24 mg, 0.15 mmol) and reac-
tion the mixture was further stirred for 10 min, followed by the ad-
dition of iodobis(acetoxy)benzene (558 mg, 1.73 mmol). The
mixture was stirred for 45 min and then diluted with CH2Cl2 (5 mL).
The mixture was washed with sat. aq Na2S2O3 (5 mL) and extracted
with CH2Cl2 (3 × 5 mL). The combined organic extracts were
washed with sat. aq NaHCO3 (2 mL), brine (2 mL), and dried
(Na2SO4). Removal of the solvent in vacuo followed by silica gel
column chromatography of the resulting residue using EtOAc–PE
(7:93) as eluent afforded the pure product 9 as a colorless oil; yield:
847 mg (85%); [a]D25 +24.5 (c 0.6 CHCl3).
IR (neat): 3306, 2120 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.81–2.10 (m, 2 H), 2.01 (t, J = 4
Hz, 1 H), 2.47 (dd, J = 6, 2 Hz, 2 H), 3.48–3.67 (m, 2 H), 3.67–3.85
(m, 1 H), 4.38–4.51 (m, 2 H), 4.46 (d, J = 12 Hz, 1 H), 4.66 (d,
J = 12 Hz, 1 H), 7.15–7.45 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 24.0, 34.3, 66.5, 70.2, 71.6, 72.9,
74.1, 80.9, 127.5, 127.6, 127.7, 127.8, 128.3 (2 C), 138.3, 138.4.
ESIMS: m/z = 295 [M + H]+, 317 [M + Na]+.
IR (CHCl3): 2214, 1715, 1671, 1610 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.01 (d, J = 8 Hz, 3 H), 1.04 (s, 9
H), 1.70–1.87 (m, 2 H), 1.87–2.00 (m, 2 H), 2.50–2.70 (m, 4 H),
3.50–3.65 (m, 2 H), 3.79–3.95 (m, 2 H), 4.40–4.50 (m, 3 H), 4.63
(d, J = 12 Hz, 1 H), 7.20–7.45 (m, 16 H), 7.60–7.70 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 19.2, 23.0, 24.7, 27.0, 33.0, 34.6,
41.2, 66.2, 68.4, 71.9, 73.0, 73.8, 82.2, 90.4, 127.4, 127.57, 127.60,
127.68, 127.73, 127.8, 128.36, 128.38, 129.5, 129.6, 134.0, 134.5,
135.77, 135.81, 138.0, 138.3, 187.8.
(2R,9S)-9,11-Bis(benzyloxy)-2-[(tert-butyldiphenylsilyl)oxy]un-
dec-6-yn-5-ol (7)
To a stirred solution of 4 (1.03 g, 3.52 mmol) in THF (30 mL) at
–78 °C was added n-BuLi (1.60 M in hexane, 2.20 mL, 3.52 mmol)
and the reaction mixture was stirred for 45 min. A solution of alde-
hyde 5 (1.00 g, 2.94 mmol) in THF (10 mL) was added dropwise to
the above mixture and it was further stirred at –78 °C for 1 h. The
reaction was quenched with sat. aq NH4Cl (5 mL) and the THF was
removed in vacuo. The obtained residue was dissolved in EtOAc
(50 mL) and the organic layer was washed with H2O (15 mL), brine
(15 mL), and dried (Na2SO4). Removal of the solvent in vacuo fol-
lowed by silica gel column chromatography of the resulting residue
using EtOAc–PE (1:9) as eluent afforded the pure product 7 as a
colorless oil; yield: 1.34 g (72%); [a]D25 +23.0 (c 0.6 CHCl3).
ESIMS: m/z = 655 [M + Na]+.
HRMS (ESI): m/z calcd for C41H48O4Si + Na [M + Na]+: 655.3219;
found: 655.3194.
(2R,9S)-2,9,11-Tris(benzyloxy)undec-6-yn-5-one (10)
Similarly, starting from compound 8 (510 mg, 1.04 mmol), product
10 was obtained as a colorless oil, following the above procedure;
yield: 426 mg (84%); [a]D25 +29.7 (c 0.5 CHCl3).
IR (CHCl3): 2253, 2215, 1670 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.18 (d, J = 6 Hz, 3 H), 1.93 (sext,
J = 6 Hz, 4 H), 2.50–2.78 (m, 4 H), 3.42–3.65 (m, 3 H), 3.83
IR (CHCl3): 3367, 2251, 1611 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.03 (d, J = 8 Hz, 3 H), 1.05 (s, 9
H), 1.55–1.77 (m, 4 H), 1.82–2.03 (m, 2 H), 2.41–2.55 (m, 2 H),
3.51–3.66 (m, 2 H), 3.69–3.79 (m, 1 H), 3.90 (sept, J = 8 Hz, 1 H),
Synthesis 2011, No. 7, 1137–1141 © Thieme Stuttgart · New York

1140
M. Singh, N. P. Argade
PAPER
(dquint, J = 6, 2 Hz, 1 H), 4.39 (d, J = 12 Hz, 1 H), 4.41–4.59 (m, 4
H), 4.63 (d, J = 10 Hz, 1 H), 7.15–7.40 (m, 15 H).
13C NMR (50 MHz, CDCl3): d = 19.4, 24.7, 30.5, 34.5, 41.4, 66.2,
70.3, 71.8, 72.9, 73.5, 73.8, 82.1, 90.5, 127.4, 127.55, 127.61,
127.67, 127.73, 128.25, 128.31, 138.0, 138.2, 138.6, 187.7.
mmol). The mixture was stirred further for 1 h at –78 °C and then
quenched with sat. aq NH4Cl (1 mL) and the THF was removed in
vacuo. To the obtained residue was added EtOAc (10 mL) and the
organic layer was washed with water (4 mL), brine (4 mL), and
dried (Na2SO4). Removal of the solvent in vacuo followed by silica
gel column chromatography of the resulting residue using EtOAc–
PE (1:4) as eluent afforded the pure product 14 as a colorless oil;
yield: 109 mg (82%); [a]D25 +28.1 (c 0.72 CHCl3).
ESIMS: m/z = 507 [M + Na]+, 523 [M + K]+.
Anal. Calcd for C32H36O4: C, 79.31; H, 7.49. Found: C, 79.47; H,
7.85.
IR (neat): 3463, 2213, 1715, 1671 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.17 (d, J = 6 Hz, 3 H), 1.60–2.05
(m, 4 H), 2.65 (d, J = 6 Hz, 2 H), 2.66 (t, J = 6 Hz, 2 H), 3.50–3.65
(m, 2 H), 3.65–3.90 (m, 2 H), 4.40–4.55 (m, 2 H), 4.50 (d, J = 10
Hz, 1 H), 4.64 (d, J = 10 Hz, 1 H), 7.20–7.40 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 23.4, 24.6, 32.9, 34.6, 41.9, 66.2,
66.9, 71.8, 73.0, 73.8, 82.1, 91.0, 127.6, 127.68, 127.74, 127.8,
128.3 (2 C), 138.0, 138.2, 188.0.
(2R,9S)-9,11-Bis(benzyloxy)-2-[(tert-butyldiphenylsilyl)oxy]un-
decan-5-one (11)
To a stirred solution of 9 (0.50 g, 0.79 mmol) in EtOAc (10 mL) at
r.t. was added 10% Pd/C (50 mg). The reaction mixture was stirred
under H2 atmosphere at balloon pressure for 1 h and filtered through
a pad of Celite. Removal of the solvent in vacuo followed by silica
gel column chromatography of the residue using EtOAc–PE (7:93)
as eluent afforded the pure product 11 as a colorless oil; yield: 0.50
g (~100%); [a]D25 +11.5 (c 1.1 CHCl3).
ESIMS: m/z = 417 [M + Na]+, 433 [M + K]+.
Anal. Calcd for C25H30O4: C, 76.11; H, 7.66. Found: C, 76.22; H,
7.61.
IR (CHCl3): 1713 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.04 (d, J = 8 Hz, 3 H), 1.04 (s, 9
H), 1.40–1.80 (m, 6 H), 1.84 (q, J = 6 Hz, 2 H), 2.22–2.55 (m, 4 H),
3.47–3.70 (m, 3 H), 3.88 (sext, J = 6 Hz, 1 H), 4.48 (s, 4 H), 7.20–
7.50 (m, 16 H), 7.60–7.75 (m, 4 H).
13C NMR (50 MHz, CDCl3): d = 19.2, 19.4, 23.2, 27.0, 32.9, 33.6,
34.2, 38.3, 42.6, 66.8, 68.7, 71.1, 73.0, 75.8, 127.4, 127.45, 127.53,
127.7, 127.8, 128.29, 128.31, 129.5, 129.6, 134.2, 134.5, 135.76,
135.81, 138.4, 138.7, 210.8.
2-[(2R,5R,7R)-2-Methyl-1,6-dioxaspiro[4.5]decan-7-yl]ethanol
(13)
To a stirred solution of 10 (150 mg, 0.30 mmol)/12 (200 mg, 0.50
mmol)/14 (100 mg, 0.25 mmol) in MeOH (5 mL) at r.t. was added
10% Pd/C (20 mg). The reaction mixture was stirred under an atmo-
sphere of H2 at 60 psi pressure for 8 h and filtered through a pad of
Celite. Removal of the solvent in vacuo followed by silica gel col-
umn chromatography of the resulting residue using EtOAc–PE
(1:3) as eluent afforded the pure product 13 as a colorless oil;6e
yield: 50/85/44 mg (82/85/87%); [a]D25 +65.4 (c 0.76 CHCl3).
ESIMS: m/z = 654 [M + NH4]+, 659 [M + Na]+.
Anal. Calcd for C41H52O4Si: C, 77.31; H, 8.23. Found: C, 77.64; H,
8.37.
IR (CHCl3): 3368, 1613 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.25 (d, J = 5 Hz, 3 H), 1.27–1.37
(m, 1 H), 1.40–1.48 (m, 1 H), 1.51–1.56 (m, 1 H), 1.62–1.93 (m, 8
H), 2.04–2.18 (m, 1 H), 3.03 (br s, 1 H), 3.72–3.80 (m, 2 H), 4.03
(tq, J = 10, 5 Hz, 1 H), 4.03 (sext, J = 10 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 20.1, 21.2, 30.8, 31.1, 33.2, 37.6,
38.0, 62.2, 71.8, 74.0, 106.2.
(2R,9S)-9,11-Bis(benzyloxy)-2-hydroxyundecan-5-one (12)
To a stirred solution of compound 11 (400 mg, 0.63 mmol) in THF
(5 mL) at 0 °C was added TBAF (1 M in THF, 1.25 mL, 1.25 mmol)
and the reaction mixture was stirred for 6 h at r.t. To the mixture was
added sat. aq NH4Cl (5 mL) and the THF was removed in vacuo.
The obtained residue was dissolved in EtOAc (20 mL), and the or-
ganic layer was washed with brine (5 mL) and dried (Na2SO4). Re-
moval of the solvent in vacuo followed by silica gel column
chromatography of the resulting residue using EtOAc–PE (3:7) as
eluent afforded the pure product 12 as a colorless oil; yield: 230 mg
(92%); [a]D25 +8.0 (c 1.16 CHCl3).
ESIMS: m/z = 223 [M + Na]+.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
IR (neat): 3445, 1712 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.17 (d, J = 6 Hz, 3 H), 1.40–1.95
(m, 8 H), 2.10 (br s, 1 H), 2.41 (t, J = 8 Hz, 2 H), 2.50 (t, J = 8 Hz,
2 H), 3.45–3.68 (m, 3 H), 3.68–3.82 (m, 1 H), 4.40–4.55 (m, 4 H),
7.20–7.40 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 19.4, 23.6, 32.5, 33.4, 34.2, 38.9,
42.7, 66.8, 67.3, 71.1, 72.9, 75.8, 127.4, 127.5, 127.6, 127.8, 128.2,
128.3, 138.3, 138.7, 211.6.
Acknowledgment
M.S. thanks CSIR, New Delhi for the award of a research fel-
lowship. N.P.A. thanks the Department of Science and Technology,
New Delhi, for financial support.
References
ESIMS: m/z = 421 [M + Na]+, 437 [M + K]+.
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