The methoxyallene approach to oxacycles, part 2: Stereoselective synthesis of 2,3-disubstituted oxepanes

Article abstract of DOI:10.1055/s-2004-834946

2,3-Disubstituted oxepanes 3 and 4 were stereoselectively synthesized from methoxyallene (1) and iodide 2. The trans stereochemistry of diol 3 was established by NMR studies of the bicyclic precursor 10, while the cis stereochemistry of 4 was secured by using the highly diastereoselective reducing agent L-Selectride. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2004-834946

PAPER
411
The Methoxyallene Approach to Oxacycles, Part 2: Stereoselective Synthesis
of 2,3-Disubstituted Oxepanes
Stereoselective
Synthe
a
sis of 2,3-D
n
isubstituted
uOxepanes el Pérez, Pilar Canoa, Generosa Gómez, Marta Teijeira, Yagamare Fall*
Departamento de Química Orgánica, Facultad de Química, Universidad de Vigo, 36200, Vigo, Pontevedra, Spain
Fax +34(98)6812262; E-mail: yagamare@uvigo.es
Received 28 July 2004; revised 11 October 2004
Dedicated to Professor P. J. Kocienski for the experience in allene chemistry we gained under his guidance at the University of
Southampton.
i
OMe
ii
Abstract: 2,3-Disubstituted oxepanes 3 and 4 were stereoselective-
ly synthesized from methoxyallene (1) and iodide 2. The trans ste-
reochemistry of diol 3 was established by NMR studies of the
bicyclic precursor 10, while the cis stereochemistry of 4 was se-
cured by using the highly diastereoselective reducing agent L-Selec-
tride.
.
CH2OH
CH2OMe
79%
78%
6
1
7
iv
80%
iii
O
.
O
Key words: natural products, methoxyallene, Michael addition,
oxepanes, toxins
TBSO MeO
TBSO MeO
97%
8
9
O
v
vi
O
Fused polycyclic ethers with trans-syn-trans stereochem-
istry are the common framework of various marine poly-
ether compounds, including brevetoxins,1 maitotoxin,2
and ciguatoxins.3 Their unusual molecular architecture
makes them challenging synthetic targets for organic
chemists. We recently reported a new method for the syn-
thesis of oxacycles using either methoxyallene4a or
furan4b,c as starting material. In this paper, we report a full
account of the methoxyallene approach, describing the
stereoselective synthesis of trans- and cis-2,3-disubstitut-
ed oxepanes 3 and 4 following the retrosynthetic analysis
depicted in Scheme 1.
O
63%
OMe
53%
H
5
H
O
O
vii
O
HO
O
H
10
HO
81%
H
3
Scheme 2 Reagents and conditions: (i) Me2SO4, NaOH; (ii) t-
BuOK (10%); (iii) n-BuLi/THF, –30 °C, 2; (iv) t-BuLi/THF, –70 °C,
1 h, CO2; 10% H2SO4–Et2O, 0 °C, 1 h; (v) TBAF/THF, r.t., 2 h; (vi)
TMSOTf, Et3SiH, CH2Cl2, r.t., 6 h; (vii) LAH, Et2O, r.t.
up,7 butenolide 9 (78% from 1). Removal of the TBS
group of 9 with TBAF then gave the bicyclic compound 5
as a single isomer through an intramolecular Michael ad-
dition (63% yield). Finally, reduction of 5 with Et3SiH
(3.0 equiv) in the presence of TMSOTf (2.4 equiv)8 in
CH2Cl2 gave compound 10 in 53% yield, presumably via
oxonium ion intermediate 11 (Scheme 3; note that the ste-
reochemical course of this reaction does not depend on
whether the ring junction of 5 is cis or trans).
H
O
OMe
.
HO
O
1
HO
H
O
3
O
MeO
H
O
I
OTBS
HO
2
5
HO
H
4
Scheme 1
H
O
O
trans-2,3-Disubstituted oxepane 3 was synthesized from
propargyl alcohol (6) via methoxyallene (1) as detailed in
Scheme 2.
vi
O
O
O
O
H
OMe
10
5
Propargyl alcohol (6) was O-methylated with dimethyl
sulfate giving 3-methoxyprop-1-yne (7).5 Isomerization
of 7 with potassium tert-butoxide afforded methoxyallene
(1) in high yield.6 Sequential metalation, alkylation, met-
alation and carboxylation of 1 afforded, after acidic work-
O
O
O
11
HSiEt3
SYNTHESIS 2005, No. 3, pp 0411–0414
Advanced online publication: 03.12.2004
x
x
.
x
x
.2
0
0
5
Scheme 3
DOI: 10.1055/s-2004-834946; Art ID: T08904SS
© Georg Thieme Verlag Stuttgart · New York

412
M. Pérez et al.
PAPER
1
The structure of 10 was determined from its H and 13C
NMR, NOE, NOESY, COSY and HMBC spectra
(Figure 1).
trometer at 400 and 100.61 MHz, respectively, using TMS as inter-
nal standard (chemical shifts in d values, J in Hz). Mass
spectrometry was carried out with a Hewlett Packard 5988A spec-
trometer. Flash chromatography (FC) was performed on silica gel
(Merck 60, 230–400 mesh); analytical TLC was performed on
plates precoated with silica gel (Merck 60 F254, 0.25 mm).
1.9%
2.6%
H
H
H
H
3-Methoxypropyne (7)
H
H
O
To a mixture of propargyl alcohol 6 (168 g, 174 mL, 2.99 mol) and
H2O (132 mL) was added a 50% aq solution of NaOH (330 g), and
the mixture was stirred with a mechanical stirrer. The temperature
was brought from 70 °C to which it had risen to 40 °C, and was kept
below 60 °C during addition of dimethyl sulfate (225 g, 169 mL,
1.78 mol). After stirring at 50–60 °C for 2 h, distillation gave a prod-
uct that came over at 61–62 °C, which was dried (CaCl2) overnight.
Finally, redistillation of this product at atmospheric pressure using
a Dufton column and a cooled receiver afforded 166.4 g of 7 (79%);
colorless oil; bp 60 °C/760 Torr.
O
2.8%
O
1.3%
H
H
1.8%
10
Figure 1 NOE correlations for 10
The synthesis of cis-oxepane diol 4 was achieved using
the highly diastereoselective L-Selectride reduction of ke-
tone 13 (Scheme 4).
1H NMR (CDCl3): d = 4.01 (2 H, s, CH2), 3.31 (3 H, s, OCH3), 2.35
(1 H, s, CH).
13C NMR (CDCl3): d = 79.2 (C), 74.3 (CH), 59.2 (CH2), 57.0 (CH3).
Bicyclic lactone 5 was opened using LiAlH4 in the pres-
ence of BF3·OEt2 to afford a 91% yield of 11 as a mixture
of diastereoisomeric diols (3 and 4). Selective protection
of the primary alcohol of 11 afforded 12 in 86% yield,
which was oxidized with tetrapropylammonium perruth-
enate (TPAP) to give ketone 13 in 95% yield. Reduction
of 13 with L-Selectride afforded stereoselectively alcohol
14 (76% yield). The tert-butyldimethylsilyl (TBS) pro-
tecting group of 14 was removed by tetrabutylammonium
fluoride (TBAF) to give finally the desired cis-diol 4 in
78% yield.
1-Methoxypropadiene (1)
t-BuOK (13.8 g, 0.118 mol) was added in one portion to propargyl
ether 7 (83 g, 1.18 mol) in a 250 mL round-bottomed flask fitted
with a double surface condenser and a mechanical stirrer. After
heating in an oil bath at 70 °C for 3 h, the mixture was allowed to
cool to r.t., the condenser and the mechanical stirrer were removed
and the reaction flask was connected to a receiver cooled with liquid
N2. Vacuum distillation without heating afforded a colorless oil that
was dried over KOH, kept in a refrigerator for 1 h, and then distilled
under N2, affording 64.8 g of 1 (78%); colorless oil; bp 50 °C/760
Torr.
In conclusion, a new and efficient method for the stereo-
selective synthesis of trans- and cis-2,3-disubstituted ox-
epanes 3 and 4 from methoxyallene has been developed.
Work is now in progress towards the enantioselective syn-
thesis of highly substituted oxepanes, precursors of bio-
logically active natural products.
1H NMR (CDCl3): d = 6.75 (1 H, t, J = 5.9 Hz, CH), 5.45 (2 H, d,
J = 5.9 Hz, CH2), 3.39 (3 H, s, OCH3).
13C NMR (CDCl3): d = 201.8 (C), 122.8 (CH), 91.0 (CH2), 55.7
(CH3).
4-Dimethyl-tert-butylsiloxy-1-iodobutane (2)
A solution of tert-butyldimethylsilyl chloride (25 g, 0.166 mol) in
MeCN (200 mL) was added to a solution of NaI (37.3 g, 0.249 mol)
in THF (50 mL). The mixture was stirred for 7 days at r.t. in the
dark, poured into hexane (200 mL), and the hexane layer was
IR spectra were recorded in a Perkin-Elmer 1640FT spectrometer.
1H and 13C NMR spectra were recorded on a Bruker AMX spec-
H
H
O
O
O
HO
TBSO
ii
i
O
HO
O
HO
OMe
86%
11
12
91%
5
H
O
H
O
TBSO
iv
iii
95%
HO
TBSO
H
O
76%
14
13
H
O
v
HO
HO
H
78%
4
Scheme 4 Reagents and conditions: (i) BF3·OEt2, LiAH4, Et2O, r.t.; (ii) TBSCl, DMF, imidazole, DMAP; (iii) TPAP, NMO, CH2Cl2; (iv) L-
Selectride, THF, –78 °C; (v) TBAF/THF, r.t., 2 h.
Synthesis 2005, No. 3, 411–414 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of 2,3-Disubstituted Oxepanes
413
washed with NaHCO3 solution containing a little Na2S2O3 (100
mL). The aqueous and MeCN layers were separated and sequential-
ly extracted with hexane (2 × 100 mL). The combined hexane lay-
ers were washed with brine (50 mL), dried (Na2SO4), and the
solvent was removed. Vacuum distillation of the residue afforded
40 g of 2 (76%); bp 132–134 °C/15 Torr.
1H NMR (CDCl3): d = 3.61 (2 H, t, J = 6.2 Hz, CH2-4), 3.20 (2 H, t,
J = 7.0 Hz, CH2-1), 1.88 (2 H, m, CH2), 1.61 (2 H, m, CH2), 0.87 (9
H, s, t-C4H9), 0.02 [6 H, s, (CH3)2Si].
7-Methoxy-2,8-dioxabicyclo[5.3.0]decan-9-one (5)
TBAF (0.83 mL of 1.0 M in THF, 0.83 mmol) was added to a solu-
tion of furanone 9 (125 mg, 0.416 mmol) in THF (5 mL) and the
mixture was stirred at r.t. for 2.5 h. It was then poured into sat. aq
NaHCO3 solution (10 mL) and extracted with Et2O (3 × 10 mL).
The combined organic layers were washed with brine (10 mL),
dried (Na2SO4), and the solvent was evaporated. The residue was
chromatographed on silica gel with 1:2.5 Et2O–hexane as eluent, af-
fording 50 mg of 5 (63%); yellowish oil; Rf 0.52 (40% EtOAc–hex-
anes).
13C NMR (CDCl3): d = 61.9 (C-4), 33.4 (C-2), 30.2 (C-3), 25.9
[C(CH3)3], 25.7 [C(CH3)3], 25.6 [C(CH3)3], 18.2 (C), 7 (C-1), –5.4
(CH3Si).
IR (KBr): 2960, 2880, 1780, 1470, 1310, 1220, 1120, 1100, 1000,
960, 905 cm–1.
1H NMR (CDCl3): d = 4.17 (1 H, ddt, J = 12.2, 2.15, 1.79 Hz, CH-
1), 3.91 (1 H, dd, J = 7.9, 2.0 Hz, CHa-3), 3.37 (1 H, m, CHb-3), 3.31
(3 H, s, OCH3), 3.01 (1 H, dd, J = 18.7, 7.8 Hz, CHa-10), 2.46 (1 H,
dd, J = 18.7, 2.0 Hz, CHb-10), 2.39 (1 H, dd, J = 14.7, 8.1 Hz, CHa-
6), 1.65–1.85 (4 H, m), 1.45 (1 H, m).
LRMS: m/z (%) = 257 (100), 215 (94), 189 (14), 185 (62), 147 (27),
129 (19), 85 (15), 83 (23), 75 (35), 73 (21).
HRMS: m/z calcd for C10H23IOSi: 314.0563; found: 314.0550.
3-Methoxy-7-tert-butyldimethylsiloxyhepta-1,2-diene (8)
n-BuLi (28.5 mL of a 2.6 M solution in hexane, 0.075 mol) was add-
ed at –25 °C to 1-methoxypropadiene (1; 5.4 g, 0.078 mol) in THF
(30 mL). The mixture was stirred for 1 h at –25 °C and then cooled
to –30 °C. Iodide 2 (18.03 g, 0.057 mol) was added to the mixture
at this temperature, and after stirring for a further 4 h, the mixture
was poured into a separating funnel containing sat. aq NaHCO3 so-
lution (33 mL) and hexane (66 mL). The organic layer was washed
with H2O (16 mL), brine (33 mL), and dried (Na2SO4). The solvent
was removed, and the residue was filtered through basic alumina us-
ing 5% Et3N in hexane as eluent, affording 9.5 g of 8 (97%); color-
less oil.
13C NMR (CDCl3): d = 174.6 (C=O), 114.5 (C-7), 84.4 (CH-1), 74.7
(CH2), 50.0 (OCH3), 36.6 (CH2), 31.6 (CH2), 30.3 (CH2), 20.8
(CH2).
LRMS: m/z (%) = 187 ([M+ + 1], 13), 186 ([M+], 16), 167 (11), 165
(14), 163 (13), 161 (10), 159 (10), 156 (14), 154 (52), 153 (100).
HRMS: m/z calcd for C9H15O4: 187.0970; found: 187.0970.
2,8-Dioxabicyclo[5.3.0]decan-9-one (10)
TMSOTf (0.09 mL, 0.48 mmol) and Et3SiH (0.09 mL, 0.597 mmol)
were added dropwise to a solution of 7 (37 mg, 0.20 mmol) in
CH2Cl2 (5 mL) at r.t., and the mixture was stirred for 6 h. H2O (5
mL) and a few drops of pyridine were added, and the product was
extracted with Et2O (5 × 5 mL). The organic layer was washed with
H2O (2 × 5 mL) and dried (Na2SO4). The solvent was evaporated,
and the residue was chromatographed on silica gel with 30–50%
EtOAc–hexanes as eluent, affording 16 mg of 10 (52%); colorless
oil; Rf 0.54 (60% EtOAc– hexanes).
1H NMR (CDCl3): d = 4.20 (1 H, ddd, J = 10.7, 8.0, 5.7 Hz, CH-1),
4.09 (1 H, dt, J = 10.7, 8.0 Hz, CH-7), 3.90 (1 H, m, CHa-3), 3.77 (1
H, m, CHb-3), 2.74 (1 H, dd, J = 16.9, 7.8 Hz, CHa-10), 2.59 (1 H,
dd, J = 16.9, 10.5 Hz, CHb-10), 2.34 (1 H, m, CHa-6), 1.7–2.0 (4 H,
m), 1.5–2.0 (1 H, m, CHb-6).
IR (KBr): 2970, 2940, 2860, 1965, 1470, 1265, 1110, 840, 780
cm–1.
1H NMR (CDCl3): d = 5.35 (2 H, d, J = 2.3 Hz, CH2-1), 3.36 (3 H,
s, OCH3), 2.12–2.31 (2 H, m, CH2-4), 1.46–1.66 (6 H, m), 0.86 (9
H, s, t-C4H9), 0.02 [6 H, s, (CH3)Si].
13C NMR (CDCl3): d = 199.5 (C), 135.2 (C), 89.8 (CH2), 63.1
(CH2), 56.0 (OCH3), 32.5 (CH2), 31.8 (CH2), 26.1 [C(CH3)3], 23.1
(CH2), 18.5 (C), –5.2 (CH3Si).
5-[4-(tert-Butyldimethylsiloxy)butyl]-5-methoxy-5H-furan-2-
one (9)
t-BuLi (6.9 mL of a 1.7 M solution in pentane, 11.7 mmol) was add-
ed to a solution of 8 (2.9 g, 11.3 mmol) in THF (15 mL) at –70 °C,
and the mixture was stirred for 1 h. Dry CO2 was then bubbled
through it for 15 min, after which it was poured into a mixture of
10% H2SO4 (10%, 75 mL) and Et2O (30 mL) at 0 °C. After stirring
at this temperature for 1 h, the organic layer was separated and the
aqueous phase was extracted with Et2O (2 × 50 mL). The combined
organic layers were washed with brine and dried (Na2SO4). The sol-
vent was evaporated, and the residue was chromatographed on sili-
ca gel with 1:3 Et2O–hexane as eluent, affording 1.9 g of 9 (80%);
yellowish oil; Rf 0.65 (40% EtOAc–hexane).
1H NMR (CDCl3): d = 7.11 (1 H, d, J = 5.7 Hz, CH-4), 6.21 (1 H,
d, J = 5.7 Hz, CH-3), 3.58 (2 H, t, J = 6.0 Hz, OCH2), 3.20 (3 H, s,
OCH3), 1.38–1.93 (6 H, m), 0.86 (9 H, s, t-C4H9), 0.02 [6 H, s,
(CH3)2Si].
13C NMR (CDCl3): d = 169.9 (C=O), 153.4 (CH-4), 124.8 (CH-3),
111.2 (C), 62.6 (CH2), 51.1 (OCH3), 36.7 (CH2), 32.5 (CH2), 25.9
[C(CH3)3], 19.7 (CH2), 18.9 (C), –5.3 (CH3Si), –5.4 (CH3Si).
13C NMR (CDCl3): d = 173.4 (C=O), 84.4 (H-7), 77.0 (H-1), 71.1
(CH2-3), 36.5 (CH2-10), 30.4 (CH2-6), 28.2 (CH2-4), 22.3 (CH2-5).
HRMS: m/z calcd for C8H12O3: 156.0786; found: 156.0780.
trans-2-(2-Hydroxyethyl)-3-hydroxyoxepane (3)
To a solution of lactone 10 (0.028 g, 0.18 mmol) in anhyd Et2O (3
mL) at 0 °C was added LiAlH4 (0.033 g, 0.89 mmol) and the mix-
ture was stirred at 0 °C to r.t. for 18 h. Excess of LiAlH4 was de-
stroyed by adding a few drops of H2O at 0 °C. After filtration and
extraction with EtOAc, the aqueous phase was saturated with NaCl
and extracted with EtOAc. The combined organic phases were dried
(Na2SO4). Filtration and evaporation of solvent afforded a residue,
which was chromatographed on silica gel with EtOAc as eluent, af-
fording 23 mg of diol 3 (81%); colorless oil.
1H NMR (CDCl3): d = 3.96 (1 H, q, J = 4.9 Hz, CH-3), 3.32–3.72 (2
H, m, CH2), 3.63–3.52 (2 H, m, CH2-7), 3.40–3.35 (1 H, m, CH-2),
2.03–1.90 (2 H, m, CH2), 1.80–1.52 (6 H, m, CH2-4, CH2-5, CH2-6).
13C NMR (CDCl3): d = 84.7 (H-2), 75.3 (H-3), 71.2 (CH2-7), 60.7
(CH2-2¢), 36.3 (CH2-1¢), 35.8 (CH2-4), 30.3 (CH2-6), 20.5 (CH2-5).
LRMS: m/z (%) = 269 (38), 253 (25), 243 (20), 216 (18), 215 (100),
213 (11), 211 (11), 201 (14), 187 (21), 185 (10), 171 (35), 155 (14),
154 (12).
HRMS: m/z calcd for C8H14O2 [M – H2O]: 142.0994; found:
142.0991.
HRMS: m/z calcd for C15H29O4Si: 301.1835; found: 301.1845.
Synthesis 2005, No. 3, 411–414 © Thieme Stuttgart · New York

414
M. Pérez et al.
PAPER
cis- and trans-2-(2-Hydroxyethyl)-3-hydroxyoxepane (11)
To a solution of 5 (4.4 g, 23.5 mmol) in anhyd Et2O (200 mL) at r.t.
was added BF3·OEt2 (7 mL, 56.4 mmol) and the mixture was stirred
for 1 h. It was then cooled to 0 °C before adding LiAlH4 (8.9 g, 235
mmol). The end of the reaction was monitored by TLC analysis. At
the end of the reaction, excess LiAlH4 was carefully destroyed by
adding a few drops of H2O at 0 °C. After filtration and extraction
with EtOAc, the aqueous phase was saturated with NaCl and ex-
tracted with EtOAc. The combined organic phases were dried
(Na2SO4). Filtration and evaporation of solvent afforded a residue
which was chromatographed on silica gel with EtOAc as eluent,
giving 3.4 g of diol 11 (as an inseparable mixture of diols 3 and 4);
yield: 91%; colorless oil.
the mixture was stirred at r.t. At the end of the reaction (TLC con-
trol), aq sat. solution of NaHCO3 (3 mL) was added and the product
was extracted with EtOAc. The aqueous phase was saturated with
NaCl and extracted with EtOAc. The combined organic phases
were dried (Na2SO4). Filtration and evaporation of solvent afforded
a residue, which was chromatographed on silica gel with EtOAc as
eluent, providing 8.7 mg of diol 4 (78%); colorless oil.
1H NMR (CDCl3): d = 3.82–3.65 (6 H, m), 2.49 (2 H, br s), 2.04–
2.00 (4 H, m), 1.99–1.51 (4 H, m).
13C NMR (CDCl3): d = 77.9 (CH-2), 71.9 (CH-3), 69.3 (CH2-7),
60.3 (CH2-2¢), 36.7 (CH2-1¢), 35.5 (CH2-4), 29.8 (CH2-6), 19.4
(CH2-5).
HRMS: m/z calcd for C8H16O3: 160.1099; found: 160.1107.
cis- and trans-2-(2-tert-Butyldimethylsilyloxyethyl)-3-hydroxy-
oxepane (12)
To a solution of diol 11 (2.2 g 13.5 mmol) in DMF (80 mL) were Acknowledgment
added imidazole (1.8 g, 27 mmol), DMAP (catalytic amount) and
This work was supported by a grant from the Xunta de Galicia
(PGIDIT04BTF301031PR). M. T. thanks the Xunta de Galicia for
a Parga Pondal contract.
TBSCl (2.2 g, 14.8 mmol). The mixture was stirred at r.t. overnight,
quenched with aq NH4Cl solution and extracted with Et2O. The or-
ganic phase was washed with H2O and brine. After drying (Na2SO4)
and evaporation of solvent, the residue was chromatographed on sil-
ica gel using 20% EtOAc–hexane as eluent, to afford 3.2 g of dia-
stereomeric alcohols 12 (86%); colorless oil.
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1H NMR (CDCl3): d = 4.24–4.18 (1 H, ddt, J = 8.5, 4.8, 1.8 Hz, CH-
2), 3.89–3.86 (1 H, dd, J = 8.8, 4.2 Hz, CH-4), 3.73–3.70 (2 H, dd,
J = 6.8, 5.4 Hz, CH2-2¢), 3.32–3.25 (1 H, dt, J = 2.3, 9.1 Hz, CH-7),
2.94–2.87 (1 H, dt, J = 9.9, 2.6 Hz, CH-7), 2.40–2.35 (1 H, dq,
J = 5.0, 1.9 Hz, CH-1¢), 1.96–1.86 (3 H, m, CH-1¢, CH2-6), 1.85–
1.69 (2 H, m, CH2-5), 0.87 (9 H, s, t-C4H9Si), 0.03 (6 H, s, CH3Si).
13C NMR (CDCl3): d = 274.1 (C=O), 84.0 (CH), 73.1 (CH2), 58.5
(CH2), 41.5 (CH2), 36.0 (CH2), 31.2 (CH2), 25.9 [C(CH3)3Si], 23.8
(CH2), 18.3 (CSi), –5.4 (CH3Si).
HRMS: m/z calcd for C14H29O3Si: 273.1886; found: 273.1894.
2-(2-tert-Butyldimethylsilyloxyethyl)-3-hydroxyoxepane (14)
To a solution of ketone 13 (0.03 g, 0.111 mmol) at –78 °C was add-
ed L-Selectride (0.278 mL of 1.0 M solution in THF, 0.278 mmol).
At the end of the reaction (TLC control), aq sat. NH4Cl solution (2
mL) was added and the mixture was stirred at r.t. for 30 min and ex-
tracted with EtOAc. After drying (Na2SO4) the extract and evapora-
tion of the solvent, the residue was chromatographed on silica gel
using 10% EtOAc–hexane to afford 23 g of alcohol 14 (76%); col-
orless oil.
1H NMR (CDCl3): d = 3.80–3.61 (6 H, m), 1.92–1.80 (2 H, m),
1.72–1.53 (6 H, m), 0.88 (9 H, s, t-C4H9Si), 0.04 [6 H, s, (CH3)2Si].
13C NMR (CDCl3): d = 76.0 (CH-2), 71.8 (CH-3), 69.3 (CH2-7),
59.5 (CH2-2¢), 36.6 (CH2-1¢), 36.0 (CH2-4), 30.1 (CH2-6), 25.9
[C(CH3)3Si], 19.6 (CH2-5), 18.2 (CSi), –5.4 [(CH3)2Si).
(4) (a) Fall, Y.; Gomez, G.; Fernández, C. Tetrahedron Lett.
1999, 40, 8307. (b) Fall, Y.; Vidal, B.; Alonso, D.; Gómez,
G. Tetrahedron Lett. 2003, 44, 4467. (c) Pérez, M.; Canoa,
P.; Gómez, G.; Terán, C.; Fall, Y. Tetrahedron Lett. 2004,
44, 5207.
(5) Reppe, W. Liebigs Ann. Chem. 1955, 596.
(6) (a) Weiberth, F. J.; Hall, S. S. J. Org. Chem. 1985, 50, 5308.
(b) Zimmer, R. Synthesis 1993, 165. (c) Hoff, S.;
Brandsma, L.; Arens, J. F. Recl. Trav. Chim. Pays-Bas 1968,
87, 916.
(7) (a) Derguini, F.; Linstrumelle, G. Tetrahedron Lett. 1989,
25, 5763. (b) Kocienski, P. J.; Fall, Y.; Whitby, R. J. Chem.
Soc., Perkin Trans. 1 1989, 841.
(8) Matsuo, G.; Hinou, H.; Koshino, H.; Suenaga, T.; Nakata, T.
Tetrahedron Lett. 2000, 41, 903.
HRMS: m/z calcd for C14H31O3Si: 275.2042; found: 275.2051.
cis-2-(2-Hydroxyethyl)-3-hydroxyoxepane (4)
TBAF (0.055 mL of a 1.0 M sln in THF, 0.055 mmol) was added to
a solution of alcohol 14 (0.015g, 0.055 mmol) in THF (1 mL) and
Synthesis 2005, No. 3, 411–414 © Thieme Stuttgart · New York