Stereoselective synthesis of syn-2,7-disubstituted-4,5-oxepenes

Article abstract of DOI:10.1016/S0040-4020(02)00046-7

An efficient synthesis of the title compounds as pure enantiomers is reported. The method is based on the intramolecular trapping of a carbocation generated by acid treatment of exo-Co₂(CO)₆-propargyl alcohols by a stereochemically c

Full text of DOI:10.1016/S0040-4020(02)00046-7

TETRAHEDRON
Pergamon
Tetrahedron 58 02002) 1913±1919
Stereoselective synthesis of syn-2,7-disubstituted-4,5-oxepenes
   Â
David D. Dõaz, Juan M. Betancort, Fernando R. P. Crisostomo, Tomas Martõn
p
 Â
and Võctor S. Martõn
   Â
Instituto Universitario de Bio-Organica `Antonio Gonzalez', Universidad de La Laguna, C/Astrofõsico Francisco Sanchez,
2, 38206 La Laguna, Tenerife, Spain
Received 2 October 2001; accepted 9 November 2001
AbstractÐAn ef®cient synthesis of the title compounds as pure enantiomers is reported. The method is based on the intramolecular trapping
of a carbocation generated by acid treatment of exo-Co20CO)6-propargyl alcohols by a stereochemically controlled secondary hydroxy group
located in a suitable chain. q 2002 Elsevier Science Ltd. All rights reserved.
An interesting and increasingly large group of marine
products is a series of nonterpenoid C15-metabolites
generically named lauroxanes that derive from fatty acid
metabolism 0acetogenins).1 The structural diversity of this
kind of molecule is very wide, but all have in common the
presence of polysubstituted cyclic ethers with a de®ned
stereochemistry in the substituents and a ring size varying
from ®ve to nine members. Among such structural diversity
a particularly interesting family are those compounds
having the oxepane 07-membered oxa-cyclic) ring. The
common structural feature is the presence of 2,7-dialkyl-
substituents with one or more halide atoms incorporated at
different positions, one of which is usually located in an
alkyl group in the a-carbon relative to the ring. A few
representative lauroxepanes isolated from different species
of red seaweeds of the genus Laurencia are outlined in
Fig. 1.2 Seven-membered oxacycles occur also in many
other interesting natural compounds such as the marine
polycyclic toxins.1,3 The structural complexity, novelty
and biological activity of these compounds have made
them very attractive synthetic targets.4
As a part of our program directed to the synthesis of marine
natural products5 we developed a general procedure for the
synthesis of cyclic ethers based on an intramolecular
Nicholas reaction6 in which a hydroxy group located in a
suitable chain attacks a carbocation generated by acid treat-
ment of exo-Co20CO)6-propargyl alcohols leading to cyclic
ethers with a ring size ranging from 6- to 9-membered rings
0Scheme 1).7
Taking advantage of such a methodology we envisioned a
way to synthesize 2,7-dialkyl-oxepenes, con®dent that with
Figure 1. Representative examples of lauroxepanes.
Scheme 1.
Keywords: marine metabolites; oxepenes; Nicholas reaction.
Corresponding author. Tel.: 134-922-318579; fax: 134-922-318571; e-mail: vmartin@ull.es
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020002)00046-7

Â
D. D. Dõaz et al. / Tetrahedron 58 12002) 1913±1919
1914
the suitable linear precursor we would be able to control the
stereochemistry in the cyclization step. Outlined herein are
our studies directed to the stereocontrolled synthesis of 2,7-
dialkyl oxepenes by an intramolecular Nicholas reaction
0Scheme 2).
Scheme 2.
In an attempt to explore the scope and limitations of our
methodology we ®rst synthesized the diastereomeric
mixture of racemic diol 7 0RˆMe, R0ˆC5H11-n) 0Scheme
3). Racemic glycidol was protected as the TBDPS-ether 3
and treated with the lithium salt of the THP-ether 4 of
commercially available 4-pentyn-2-ol yielding the dipro-
tected triol 5. Lindlar hydrogenation and further O-silyl
deprotection provided stereoselectively the Z-diol 6. Oxida-
tive cleavage of the diol, treatment of the resulting crude
aldehyde with the lithium acetylide of 1-heptyne and
cleavage of the THPO-ether provided the diol 7.
In order to probe our idea about the capability of the second-
ary nucleophilic carbinol to control the stereochemistry in
the cyclization step we submitted 7 to Co20CO)8 obtaining in
almost quantitative yield the corresponding Co20CO)6±
alkyne complex 2 0RˆMe, R0ˆC5H11-n). Acidic treatment
followed by acetylene demetalation8 provided exclusively
the syn-diastereoisomer of 0^)-1. It should be pointed out
that the cyclization step is very fast 0ca. 5 min) and that the
stereochemical results are similar from 2208C to room
temperature. We think that a possible explanation of the
strong selectivity could be related to the formation of a
transition state such as 8 in which the more bulky groups,
the metallic complexes alkyne and the alkyl substituent at
the secondary nucleophilic carbinol, occupy a pseudo-
equatorial position 0Scheme 4).9
Scheme 3.
In light of these results we decided to obtain 2,7-disubsti-
tuted-4,5-oxepenes as pure enantiomers to show that our
Scheme 4.
Scheme 5.

Â
D. D. Dõaz et al. / Tetrahedron 58 12002) 1913±1919
1915
methodology can be easily applied for the synthesis of
1. Experimental
1.1. Materials and methods
several natural compounds. We directed our attention to
the known homopropargylic alcohol 9, easily available on
a multigram scale10 from 0R)-glyceraldehyde.11 Protection
as TBS-ether and further alkylation with allylic bromide and
the assistance of Cu0I) provided the skipped enyne 10 that
was submitted to dihydroxylation and further Lindlar's
hydrogenation providing the diastereomeric mixture of
diols 11 0Scheme 5). With these products in our hands a
similar sequence to that performed before, namely oxidative
cleavage, lithium acetylides addition provided 12 0RˆTMS
or ±CH2OBn) as a stereoisomer mixture at the propargylic
position. Silyl-cleavage affords the diols 13 0RˆH or
±CH2OBn). Finally, 13 was complexed and the resulting
Co20CO)6±acetylene treated with Lewis acid at 2208C
obtaining the corresponding cyclic ether that after demetal-
ation yielded 14 0RˆH or ±CH2OBn) as a mixture of
epimers at C7 02:1) regardless the nature of the acetylenic
substituent.12 Interestingly, when the reaction was
performed at higher temperature the deprotection of the
acetonide competes with the ring formation producing a
mixture.
1H NMR spectra were recorded at 400 and 300 MHz, 13C
NMR spectra were recorded at 75 MHz, and chemical shifts
are reported relative to internal Me4Si. Optical rotations
were determined for solutions in chloroform. Column
Ê
chromatography was performed on Merck silica gel, 60 A
and 0.2±05 mm. Compounds were visualized by use of UV
light and/or 2.5% phosphomolybdic acid in ethanol with
heating. All solvents were puri®ed by standard techniques.15
Reactions requiring anhydrous conditions were performed
under nitrogen. Anhydrous magnesium sulfate was used for
drying solutions.
1.1.1. Preparation of 1-methyl-3-butynyl tetrahydro-2H-
pyran-2yl ether )4). To a stirred solution of the 4-pentyn-2-
ol 010 g, 119 mmol) in dry CH2Cl2 0300 mL) under argon
was added dihydropyran 021.7 mL, 238 mmol) and a
catalytic amount of pyridinium p-toluenesulfonate at 08C.
The reaction was allowed to warm to rt and stirred for 6 h.
The reaction mixture was poured into ice-water and
extracted with CH2Cl2 02£100 mL). The combined organic
phases were washed with brine 0200 mL), dried and concen-
trated. The crude obtained was puri®ed by ¯ash chromato-
Although the overall results regarding the synthesis of the
oxacycles were satisfactorily achieved, we worried about
the role of the additional stereocenter in the linear precursor
0compared with the model 7) over the stereochemistry in the
cyclization reaction.13 In order to probe such in¯uence we
selectively deprotected the acetonide14 yielding the diol 15
that was oxidatively cleavage to the corresponding aldehyde
and further homologated to the a,b-unsaturated ester 16
0Scheme 6). Fortunately, when we followed a similar cycli-
zation sequence of that outlined above we obtained the
highly functionalized oxepene 17 as the only stereoisomer.
1
graphy, yielding 4 017.5 g, 88% yield) as an oil: H NMR
0CDCl3) d 1.21 0d, Jˆ6.2 Hz, 3H), 1.28 0d, Jˆ6.3 Hz, 3H),
1.49 0m, 9H), 1.67 0m, 2H), 1.79 0m, 2H), 1.95 0ddd, Jˆ7.4,
2.6, 2.6 Hz, 1H), 2.32 0m, 3H), 2.51 0ddd, Jˆ16.0, 5.1,
2.7 Hz, 1H), 3.45 0m, 2H), 3.89 0m, 4H), 4.67 0m, 1H),
4.71 0m, 1H); 13C NMR 0CDCl3) d 18.8 0q), 19.5 0t), 19.7
0t), 21.0 0q), 25.4 0t), 25.4 0t), 25.7 0t), 27.1 0t), 30.8 0t), 30.9
0t), 62.3 0t), 62.6 0t), 69.7 0s), 69.7 0s), 70.6 0d), 70.9 0d), 81.1
0d), 81.4 0d), 96.7 0d), 97.7 0d). IR 0CHCl ) n
Åmax
0cm21
)
3
In summary, we have described an ef®cient method to
obtain enantiomerically pure syn-2,7-disubstituted-4,5-
oxepenes with enough functionalities in the lateral chains
to perform the necessary conversions to some marine
natural products with the 7-membered ring as the key struc-
tural feature. Synthetic studies of some of such compounds
are under study and will be published in due course.
3308, 3010, 2946, 2853, 2360, 1126, 1030. MS m/z 0relative
intensity) 169 0M11)1 02), 149 0100), 117 025), 105 011), 97
015), 85 021), 31 055). Anal. Calcd for C10H16O2: C, 71.39;
H, 9.59. Found: C, 71.40; H, 9.61.
1.1.2. Preparation of 1-)tert-butyl-diphenyl-silanyloxy)-
7-)tetrahydro-2H-pyran-2-yloxy)-4-octyn-2-ol )5). To a
stirred solution of the alkyne 4 02.7 g, 16 mmol) dissolved
in dry THF 0160 mL) under argon was added n-butyl lithium
1.9 M in n-hexane 08 mL, 15.2 mmol) at 2788C. After the
addition, the reaction was maintained with stirring for
15 min, after which time, 1 equiv. of BF3´Et2O 02.03 mL,
16 mmol) was added. After 5 min, tert-butyl-dimethyl-
oxiranylmethoxy-silane 01.6 g, 8.5 mmol) in dry THF
010 mL) was added slowly. The reaction mixture was stirred
for 30 min, until TLC showed complete conversion. The
mixture was poured into a saturated aqueous solution of
NaHCO3 0100 mL) and ether 0100 mL), both phases were
separated and the aqueous phase was washed with ether
02£50 mL). The combined organic phases were dried,
concentrated and the obtained crude was puri®ed by ¯ash-
chromatography, to yield 5 02.96 g, 77% yield) as an oil: 1H
NMR 0CDCl3) d 1.04 0d, Jˆ6.3 Hz, 6H), 1.09 0s, 18H), 1.17
0d, Jˆ6.12 Hz, 3H), 1.18 0d, Jˆ6.0 Hz, 3H), 1.27 0ddd,
Jˆ14.5, 14.5, 6.1 Hz, 4H), 1.51 0m, 12H), 1.68 0m, 4H),
1.83 0m, 4H), 2.30 0m, 4H), 2.47 0m, 8H), 2.65 0d,
Jˆ5.2 Hz, 2H), 2.78 0d, Jˆ5.3 Hz, 2H), 3.48 0m, 4H),
3.73 0m, 8H), 3.89 0m, 12H), 4.67 0m, 2H), 4.73 0m, 2H),
Scheme 6.

Â
D. D. Dõaz et al. / Tetrahedron 58 12002) 1913±1919
1916
7.37 0m, 24H), 7.64 0m, 16H); 13C NMR 0CDCl3) d 19.2 0q),
19.3 0s), 19.7 0t), 19.8 0t), 21.1 0q), 23.6 0t), 23.8 0t), 25.5 0t),
26.1 0t), 26.9 0q), 27.0 0t), 27.5 0t), 30.9 0t), 31.1 0t), 62.6 0t),
62.7 0t), 66.5 0t), 66.5 0t), 66.5 0t), 67.9 0t), 70.5 0d), 71.1 0d),
71.2 0d), 71.3 0d), 77.3 0s), 77.4 0s), 77.4 0s), 79.3 0s), 79.3
0s), 79.7 0s), 79.8 0s), 97.0 0d), 97.6 0d), 127.8 0d), 129.8 0d),
THF 022 mL) under argon was added dropwise 0.9 equiv.
of n-BuLi 01.28 mL, 2.43 mmol, 1.9 M in n-hexane) at
2788C. The reaction was allowed to warm to 2208C and
stirred for 15 min, after which time was added the aldehyde
in dry THF 05 mL) at 2788C. The reaction mixture was
stirred for 1 h, after which time TLC showed complete
conversion. The reaction was poured into NH4Cl saturated
aqueous solution 020 mL) and ether 020 mL) and the
aqueous phase extracted with ether 02£10 mL). The
combined organic solutions were dried over MgSO4 and
concentrated and the crude was used without puri®cation.
129.8 0d), 133.1 0s), 133.2 0s), 135.6 0d). IR 0CHCl ) n
3
Åmax
0cm21) 3572, 3009, 2932, 2859, 1428, 1113, 1074; MS m/z
0relative intensity): 423 0M257)1 01), 379 02), 339 017), 295
04), 261 018), 241 051), 199 0100), 163 029), 135 016); Anal.
Calcd for C29H40O4Si: C, 72.46; H, 8.39. Found: C, 72.22;
H, 8.50.
The crude alcohol was dissolved in MeOH and a catalytic
amount of concentrated HCl was added at 08C. The reaction
was stirred for 1 h, after which time TLC showed that the
starting material had disappeared, and then Et3N was added
at 08C until neutral pH was reached. The reaction was
concentrated and puri®ed by column chromatography,
yielding the diol 7 0185 mg, 61% yield) as an oil: 1H
NMR 0CDCl3) d 0.90 0dd, Jˆ7.1, 7.1 Hz, 6H), 1.22 0d,
Jˆ6.3 Hz, 3H), 1.23 0d, Jˆ6.3 Hz, 3H), 1.33 0m, 8H),
1.51 0dddd, Jˆ7.1, 7.1, 7.1, 7.1 Hz, 4H), 1.61 0bs, 4H),
2.20 0ddd, Jˆ7.2, 7.2, 1.9 Hz, 4H), 2.22 0m, 1H), 2.29 0m,
1H), 2.45 0m, 1H), 2.54 0m, 1H), 3.86 0m, 2H), 4.41 0m, 1H),
4.46 0m, 1H), 5.68 0m, 4H); 13C NMR 0CDCl3) d 13.9 0q),
18.6 0t), 22.2 0t), 23.0 0q), 23.1 0q), 28.3 0t), 31.0 0t), 35.7 0t),
36.1 0t), 37.0 0t), 61.8 0d), 61.9 0d), 67.4 0d), 67.4 0d), 80.6
0s), 80.7 0s), 85.8 0s), 86.0 0s), 127.3 0d), 127.6 0d), 129.1 0d),
1.1.3. Preparation of )4Z)-7-)tetrahydropyran-2-yloxy)-
4-octen-1,2-diol )6). A mixture of 5 04.7 g, 9.71 mmol) and
Lindlar's catalyst 050 mg) in dry EtOAc 063 mL) was stirred
at room temperature under a H2 atmosphere 0<1 atm). The
reaction was stirred for 2 h, after which time TLC showed
the end of the reaction. The solution was ®ltered through a
pad of Celite and the ®lter was washed with EtOAc. The
combined organic phases were concentrated, and the crude
obtained was used without puri®cation.
To a stirred solution of the alkene in dry THF 050 mL) under
argon was added n-tetrabutylammonium ¯uoride 1 M in
THF 011.7 mL, 11.7 mmol) at 08C. The reaction was
allowed to warm to room temperature and stirred for 2 h.
The reaction mixture was poured into H2O 050 mL) and
extracted with ether 02£30 mL). The combined organic
solutions were washed with brine 050 mL) and dried. The
resulting solution was concentrated and puri®ed by column
chromatography, yielding the diol 6 01.7 g, 72% yield) as an
129.2 0d). IR 0CHCl ) n 0cm21) 3456, 3008, 2975, 2933,
Åmax
3
2896, 2360, 1390, 1046, 877; MS m/z 0relative intensity):
191 0M233)1 01), 169 02), 125 024), 106 012), 91 018), 82
0100), 67 061); Anal. Calcd for C14H24O2: C, 74.95; H,
10.78. Found: C, 74.77; H, 11.01.
1
oil: H NMR 0CDCl3) d 1.14 0d, Jˆ6.2 Hz, 3H), 1.15 0d.
Jˆ6.1 Hz, 3H), 1.23 0d, Jˆ6.4 Hz, 3H), 1.24 0d, Jˆ6.3 Hz,
3H), 1.52 0m, 14H), 1.68 0m, 4H), 1.81 0m, 6H), 2.18 0m,
4H), 2.31 0m, 12H), 3.48 0m, 8H), 3.63 0m, 2H), 3.66 0m,
2H), 3.73 0m, 4H), 3.80 0dddd, Jˆ6.2, 6.2, 6.2, 1.4 Hz, 2H),
3.88 0m, 6H), 5.66 0m, 4H), 5.54 0m, 6H), 5.64 0m, 2H); 13C
NMR 0CDCl3) d 18.0 0q), 19.0 0q), 19.7 0t), 19.8 0t), 19.9 0t),
21.3 0q), 24.6 0q), 25.3 0t), 25.4 0t), 30.9 0t), 30.9 0t), 31.0 0t),
31.0 0t), 31.3 0t), 31.4 0t), 31.5 0t), 34.2 0t), 34.5 0t), 35.1 0t),
35.3 0t), 62.7 0t), 62.8 0t), 63.0 0t), 66.0 0t), 66.3 0t), 71.0 0d),
71.4 0d), 71.6 0d), 71.7 0d), 71.8 0d), 73.3 0d), 73.7 0d), 96.0
0d), 96.6 0d), 98.4 0d), 98.7 0d), 126.8 0d), 126.4 0d), 126.5
0d), 126.7 0d), 128.9 0d), 129.2 0d), 129.4 0d), 129.9 0d). IR
1.1.5. Preparation of )2Rp,7Rp)-2-hept-1-ynyl-7-methyl-
3H,6H-oxepin )1) )RˆMe, R0ˆC5H11-n). To a solution
of 7 0131 mg, 0.58 mmol) in dry CH2Cl2 06 mL) was
added Co20CO)8 0238 mg, 0.7 mmol) at room temperature.
The reaction mixture was stirred at room temperature until
TLC showed complete conversion to the hexacarbonyl-
dicobalt complex 0ca. 1 h). The mixture was ®ltered through
a pad of silica gel and concentrated to yield red±brown oil
that was used without any puri®cation.
To a stirred solution of the crude Co20CO)6 complex in dry
CH2Cl2 06 mL) under argon was added BF3´OEt2 088 mL,
0.70 mmol) at room temperature. The reaction mixture was
stirred for 20 min and poured into a saturated aqueous
NaHCO3 010 mL). The resulting mixture was vigorously
stirred for 15 min and extracted with CH2Cl2 02£15 mL).
The combined organic layers were washed with brine
010 mL), dried 0MgSO4), ®ltered and concentrated to give
the Co20CO)6 complex that was employed in the next step
without further puri®cation.
0CHCl ) n
Åmax
0cm21) 3452, 3009, 2974, 2948, 1381, 1074,
3
1029, 877. MS m/z 0relative intensity): 225 0M219)1 01),
149 02), 140 01), 101 03), 84 0100), 67 013), 55 013); Anal.
Calcd for C13H24O4: C, 63.91; H, 9.90. Found: C, 63.73; H,
10.21.
1.1.4. Preparation of )4Z)-4-tetradecen-8-yne-2,7-diol
)7). To a stirred solution of the diol 6 0330 mg,
1.35 mmol) dissolved in THF/H2O 05:1, 13.5 mL) were
added NaIO4 01.16 g, 5.4 mmol) and a catalytic amount of
tetra-butylammonium periodate at room temperature. After
1 h, the mixture was diluted with ether 020 mL) and washed
with brine 015 mL), and the aqueous phase washed with
ether 03£20 mL). The combined organic solutions were
dried over MgSO4, concentrated and the crude aldehyde
obtained was used without puri®cation.
To a stirred solution of the complexed acetylene in dry
acetone 06 mL) was added CAN 01.27 g, 2.32 mmol) in
one portion at 08C. The reaction mixture was stirred at
08C until TLC showed completion of the reaction 0ca.
5 min). The mixture was evaporated and the residue diluted
with water 010 mL) and extracted with Et2O 02£15 mL).
The combined organic solutions were dried 0MgSO4),
®ltered and concentrated. Flash column chromatography
To a solution of 1-heptyne 00.355 mL, 2.7 mmol) in dry

Â
D. D. Dõaz et al. / Tetrahedron 58 12002) 1913±1919
1917
yielded 1 0RˆMe, R0ˆC5H11-n) 083 mg, 70% overall yield)
1.1.7. Preparation of )2R and 2S, 7S)-7-)tert-butyl-
dimethyl-silanyloxy)-7-[)4R)-2,2-dimethyl-[1,3]dioxolan-
4-yl]-4-heptene-1,2-diol )11). To a stirred solution of
4-methylmorpholine N-oxide 04.34 g, 37.0 mmol) in H2O
040 mL) at room temperature, were added OsO4 06 mg,
0.02 mmol) and the alkene 10 04 g, 12.3 mmol) in THF/
acetone 01:1) 080 mL). The mixture was vigorously stirred
overnight. Then it was diluted with EtOAc 0100 mL) and
washed with a saturated solution of NaHSO3 0150 mL), the
aqueous phase was extracted with AcOEt 02£50 mL) and
the combined organic phase was washed with H2O
0150 mL) and dried over MgSO4, ®ltered and concentrated.
Flash column chromatography yielded the corresponding
diol 04.07 g, 92% yield) as a colourless oil: 1H NMR
0CDCl3) d 0.08 0s, 3H), 0.09 0s, 3H), 0.87 0s, 9H), 1.33 0s,
3H), 1.38 0s, 3H), 2.40 0m, 4H), 3.24 0br s, 2H), 3.73 0dd,
Jˆ10.6, 5.0 Hz, 2H), 3.85 0dd, Jˆ7.9, 6.2 Hz, 2H), 4.01 0dd,
Jˆ7.1, 7.1 Hz, 2H), 4.09 0dd, Jˆ12.4, 6.2 Hz, 2H); 13C
NMR 0CDCl3) d 24.7 0q), 24.4 0q), 17.9 0s), 24.9 0t),
25.3 0q), 25.7 0q), 26.6 0q), 66.1 0t), 71.4 0d), 77.5 0d),
78.1 0s), 78.8 0s), 109.1 0s). MS m/z 0relative intensity):
301 01.8) 0M2tBu)1, 187 018), 117 038), 75 097), 73
0100). Anal. Calcd for C18H34O5Si: C, 60.30; H, 9.56.
Found: C, 60.36; H, 9.77.
1
as a colourless oil: H NMR 0CDCl3) d 0.88 0dd, Jˆ6.9,
6.9 Hz, 3H), 1.24 0d, Jˆ6.2 Hz, 3H), 1.32 0m, 4H), 1.49
0dddd, Jˆ7.1, 7.1, 7.1, 7.1 Hz, 2H), 2.15 0m, 1H), 2.19
0ddd, Jˆ7.0, 7.0, 1.8 Hz, 2H), 2.31 0ddd, Jˆ16.4, 10.0,
2.3 Hz, 1H), 2.42 0dddd, Jˆ16.7, 6.6, 1.8, 1.8 Hz, 1H),
2.63 0m, 1H), 3.54 0m, 1H), 4.15 0dddd, Jˆ10.5, 1.8, 1.8,
1.8 Hz, 1H), 5.76 0m, 2H); 13C NMR 0CDCl3) d 13.9 0q),
18.8 0t), 22.2 0t), 23.1 0q), 28.3 0t), 31.1 0t), 39.1 0t), 39.3 0t),
70.4 0d), 76.6 0d), 80.2 0s), 84.5 0s), 129.1 0d), 130.3 0d). IR
0CHCl ) n
Åmax
0cm21) 3005, 2959, 2933, 2861, 2360, 1318,
3
1078, 1025. MS m/z 0relative intensity): 205 0M21)1 02),
173 09), 162 08), 123 010), 106 018), 97 011), 86 041), 82
0100); Anal. Calcd for C14H22O: C, 81.50; H, 10.75. Found:
C, 81.32; H, 10.99.
1.1.6. Preparation of tert-butyl-{)1S)-1-[)4R)-2,2-di-
methyl-1,3-dioxolan-4-yl]-6-hepten-3-ynyloxy}-dimethyl-
silane )10). To a stirred solution of the alcohol 9 03 g,
17.6 mmol) in dry CH2Cl2 088 mL) under argon were
added imidazole 01.8 g, 26.4 mmol) and tert-butylchloro-
dimethylsilane 03.45 g, 22.9 mmol) at 08C. The reaction
was allowed to warm to room temperature and stirred over-
night. Then it was poured into H2O 0100 mL) and extracted
with CH2Cl2 02£30 mL). The combined organic phases
were washed with brine 0100 mL), dried, ®ltered and
concentrated. The crude obtained was puri®ed by ¯ash
A mixture of the diol 04 g, 11.2 mmol), Lindlar catalyst
0200 mg, 5% w) and quinoline 07 mL, 0.2% w) in dry
EtOAc 0112 mL) was stirred at room temperature under a
H2 atmosphere 0<1 atm) for 30 min, after which time TLC
showed the end of the reaction. The solution was ®ltered
through a pad of Celite and the ®lter was washed with
EtOAc. The combined organic phases were concentrated,
and the crude obtained was puri®ed by ¯ash-chromato-
graphy, yielding 11 04.02 g, quantitative) as an oil: 1H
NMR 0CDCl3) d; 13C NMR 0CDCl3) d 24.7 0q), 24.4
0q), 18.0 0s), 23.1 0t), 25.0 0t), 25.3 0q), 25.6 0q), 26.6 0q),
66.0 0t), 71.5 0d), 77.4 0s), 77.6 0d), 78.6 0s), 108.9 0s), 115.7
0t), 133.0 0d). MS m/z 0relative intensity): 303 00.23)
0M2tBu)1, 245 014), 187 025), 117 020), 75 071), 73
0100). Anal. Calcd for C18H36O5Si: C, 59.96; H, 10.06.
Found: C, 59.99; H, 10.68.
chromatography affording the silyl ether 04.81 g, 96%
1
yield) as an oil: [a]25 ˆ126.5 0c 1.71, CHCl3); H NMR
D
0CDCl3) d 0.07 0s, 3H), 0.11 0s, 3H), 0.87 0s, 9H), 1.32 0s,
3H), 1.37 0s, 3H), 1.96 0t, Jˆ2.7 Hz, 1H), 2.42 0m, 2H), 3.76
0dd, Jˆ12.5, 6.3 Hz, 1H), 3.85 0dd, Jˆ8.0, 6.3 Hz, 1H), 4.00
0dd, Jˆ8.0, 6.4 Hz, 1H), 4.12 0dd, Jˆ12.5, 6.3 Hz, 1H); 13C
NMR 0CDCl3) d 24.7 0q), 24.3 0q), 18.0 0s), 24.6 0t), 25.4
0q), 25.7 0q), 26.7 0q), 66.2 0t), 70.4 0d), 71.2 0d), 77.4 0d),
80.5 0s), 109.0 0s). MS m/z 0relative intensity): 227 01.7)
0M2tBu)1, 169 076), 95 025), 75 0100), 73 091); HRMS
Calcd for C11H19O3Si 0M2tBu)1 227.11035, found
227.10922.
To a stirred solution of the alkyne 04 g, 14.1 mmol) in dry
DMF 047 mL) under argon were added sequentially K2CO3
02.74 g, 19.8 mmol), tetra-n-butylammonium bromide
0590 mg, 1.83 mmol) and copper0I) iodine 0134 mg,
0.7 mmol) at room temperature. After 10 min, allyl bromide
01.58 mL, 18.3 mmol) was added. The reaction mixture was
stirred for 60 h. Then, it was poured into H2O 0200 mL) and
extracted with ether 03£50 mL). The combined organic
phases were washed with brine 0100 mL), dried and
concentrated. The crude obtained was puri®ed by ¯ash chro-
1.1.8. Preparation of )3R and 3S, 5Z, 8S)-8-)tert-butyl-
dimethyl-silanyloxy)-8-[)4R)-2,2-dimethyl-1,3-dioxolan-
4-yl]-1-trimethylsilanyl-5-octen-1-yn-3-ol )12) )RˆTMS).
The sequence used above to obtain 7 from 6 was applied to
11 on a 3.5 g 09.7 mmol) scale, yielding 12 0RˆTMS)
03.4 g, 82% overall yield) as colorless oil: 1H NMR
0CDCl3) d 0.04 0s, 6H), 0.05 0s, 6H), 0.13 0s, 18H), 0.85
0s, 18H), 1.29 0s, 6H), 1.36 0s, 3H), 1.37 0s, 3H), 2.22 0m,
2H), 2.44 0m, 6H), 2.68 0br s, 2H), 3.76 0m, 4H), 3.94 0m,
4H), 4.32 0dd, Jˆ7.0, 5.9 Hz, 1H), 4.37 0dd, Jˆ5.8, 5.8 Hz,
1H), 5.64 0m, 4H); 13C NMR 0CDCl3) d 24.7 0q), 24.2 0q),
20.2 0q), 17.9 0s), 25.3 0q), 25.7 0q), 26.7 0q), 32.4 0t), 32.5
0t), 35.6 0t), 36.0 0t), 62.0 0d), 62.1 0d), 66.7 0t), 72.4 0d), 72.5
0d), 77.6 0d), 88.8 0s), 89.1 0s), 106.4 0s), 106.8 0s), 109.0 0s),
109.1 0s), 126.1 0d), 126.3 0d), 128.2 0d), 128.3 0d). MS m/z
0relative intensity). Anal. Calcd for C22H42O4Si2: C, 61.92;
H, 9.92. Found: C, 61.77; H, 10.08.
matography, yielding 10 04.24 g, 93% yield): [a]25
ˆ
D
1
125.4 0c 1.93, CHCl3); H NMR 0CDCl3) d 0.08 0s, 3H),
0.10 0s, 3H), 0.88 0s, 9H), 1.32 0s, 3H), 1.37 0s, 3H), 2.41 0m,
2H), 2.91 0m, 2H), 3.78 0dd, Jˆ10.6, 5.3 Hz, 1H), 3.86 0dd,
Jˆ7.0, 7.0 Hz, 1H), 4.00 0dd, Jˆ7.1, 7.1 Hz, 1H), 4.13 0dd,
Jˆ12.3, 6.0 Hz, 1H), 5.06 0d, Jˆ10.0 Hz, 1H), 5.29 0d,
Jˆ16.9 Hz, 1H), 5.78 0m, 1H); 13C NMR 0CDCl3) d 24.7
0q), 24.4 0q), 18.0 0s), 23.1 0t), 25.0 0t), 25.3 0q), 25.6 0q),
26.6 0q), 66.0 0t), 71.5 0d), 77.4 0s), 77.6 0d), 78.6 0s), 108.9
0s), 115.7 0t), 133.0 0d). MS m/z 0relative intensity): 267
03.4) 0M2tBu)1, 245 014), 209 033), 117 031), 75 090), 73
0100). HRMS Calcd for C18H32O3Si 0M)1 324.21207, found
324.21320.
1.1.9. Preparation of )1S,3Z,6R and 6S)-1-[)4R)-2,2-
dimethyl-1,3-dioxolan-4-yl]-3-octen-7-yne-1,6-diol )13)
)RˆH). The TBDPS-deprotection used above to obtain 6

Â
D. D. Dõaz et al. / Tetrahedron 58 12002) 1913±1919
1918
was applied to 12 0RˆTMS) on a 3 g 07.03 mmol) scale,
1.1.13. Preparation of )2R and 2S,7S)-2-)3-benzyloxy-
prop-1-ynyl)-7-[)4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-
3H,6H-oxepine )14) )RˆCH2OBn). The Co20CO)6±alkyne
complex formation, acidic treatment followed by
acetylene demetalation used above to obtain 0^ 1 0RˆMe,
R0ˆC5H11-n) was applied to 13 0RˆCH2OBn) on a 1 g
02.8 mmol) scale, yielding 14 0RˆCH2OBn) as a diastereo-
1
yielding 13 0RˆH) 01.39 g, 82% yield) as an oil: H NMR
0CDCl3) d 1.31 0s, 6H), 1.37 0s, 6H), 2.15±2.53 0m, 10H),
3.42 0bs, 4H), 3.64 0m, 2H), 3.86±4.00 0m, 6H), 4.33±4.43
0m, 2H), 5.60±5.68 0m, 4H); 13C NMR 0CDCl3) d 25.2 0q),
26.6 0q), 31.2 0t), 34.9 0t), 35.5 0t), 61.0 0d), 61.1 0d), 65.9 0t),
71.2 0d), 71.3 0d), 72.8 0d), 73.1 0d), 78.1 0d), 78.2 0d), 84.4
0s), 84.6 0s), 109.2 0s), 126.9 0d), 127.3 0d), 128.8 0d). MS
m/z 0relative intensity); HRMS Calcd for C13H15O3
0M2CH3)1, found.
1
isomeric mixture 0756 mg, 79% overall yield): H NMR
0CDCl3) d 1.34 0s, 3H), 1.39 0s, 3H), 2.26±2.30 0m, 1H),
2.45±2.57 02H), 2.62±2.66 0m, 1H), 3.29 0m, 1H), 3.92±
3.98 0m, 2H), 4.08±4.19 0m, 1H), 4.20 0s, 2H), 4.19±4.26
0m, 1H), 4.57 0s, 2H), 5.72±5.77 0m, 1H), 5.84±5.88 0m,
1H), 7.27±7.35 0m, 5H); 13C NMR 0CDCl3) d 25.2 0q), 26.6
0q), 26.8 0q), 33.1 0t), 33.6 0t), 35.8 0t), 38.5 0t), 57.1 0t), 57.3
0t), 60.2 0t), 66.4 0d), 67.6 0t), 67.8 0t), 70.5 0d), 71.2 0s), 71.4
0s), 74.3 0d), 77.6 0d), 77.7 0d), 80.0 0s), 81.7 0d), 82.5 0s),
84.7 0s), 85.9 0s), 109.3 0s), 109.4 0s), 127.5 0d), 127.8 0d),
128.0 0d), 128.3 0d), 128.6 0d), 130.1 0d), 130.7 0d), 137.3
0s). MS m/z 0relative intensity); HRMS Calcd for CHO
0M)1, found.
1.1.10. Preparation of )2S,7R and 7S)-2-[)4R)-2,2-
dimethyl-1,3-dioxolan-4-yl]-7-ethynyl-3H,6H-oxepine )14)
)RˆH). The sequence used above to obtain 0^)1 0RˆMe,
R0ˆC5H11-n) was applied to 13 0RˆH) on a 1 g 04.2 mmol)
scale, yielding 14 0RˆH) as a diastereoisomeric mixture
1
0629 mg, 68% overall yield): H NMR 0CDCl3) d 1.30 0s,
4.5H), 1.36 0s, 4.5H), 2.23 0m, 2H), 2.42±2.62 0m, 5.5H),
3.29 0dd, Jˆ8.3, 8.3 Hz, 1H), 3.86±3.94 0m, 3.5H), 4.03±
4.16 0m, 2.5H), 4.73 0m, 0.5H), 5.68±5.85 0m, 3H); 13C
NMR 0CDCl3) d 25.2 0q), 26.6 0q), 26.8 0q), 33.1 0t), 33.6
0t), 35.6 0t), 38.4 0t), 66.2 0d), 67.6 0t), 67.8 0t), 70.2 0d), 72.2
0d), 74.3 0d), 74.6 0s), 77.5 0d), 77.6 0d), 77.7 0d), 81.8 0d),
83.1 0d), 109.3 0s), 109.4 0s), 127.2 0d), 128.5 0d), 130.1 0d),
130.8 0d). MS m/z 0relative intensity). HRMS Calcd for
CHO 0M)1, found.
1.1.14. Preparation of )2R,3S,5Z,8R and 8S)-11-benzyl-
oxy-3-)tert-butyl-dimethyl-silanyloxy)-5-undecen-9-yne-
1,2,8-triol )15). To a solution of 12 0RˆCH2OBn) 01 g,
2.25 mmol) in MeOH 05 mL) was added pyridinium
p-toluenesulfonate 0505 mg, 2.25 mmol), the reaction was
stirred for 1 h, after which time was quenched with Et3N
until pH<7 and methanol was evaporated under vacuum.
The residue was puri®ed by chromatography column giving
the triol 15 0390 mg, 43% yield) and the unreacted substrate
12 0550 mg): 1H NMR 0CDCl3) d 0.08 0s, 6H), 0.89 0s, 9H),
2.16±2.24 0m, 1H), 2.37±2.43 0m, 1H), 2.54±2.62 0m, 1H),
3.00 0bs, 3H), 3.60±3.70 0m, 2H), 3.72±3.77 0m, 2H), 4.19
0br s, 2H), 4.58 0s, 2H), 5.52±5.72 0m, 2H); 13C NMR
0CDCl3) d 24.9 0q), 24.4 0q), 14.1 0s), 17.9 0s), 25.6 0q),
25.8 0q), 31.4 0t), 31.5 0t), 35.1 0t), 35.9 0t), 57.4 0t), 60.4 0s),
61.5 0d), 61.6 0d), 63.6 0t), 71.7 0t), 72.9 0d), 73.0 0d), 77.4
0d), 80.7 0s), 81.1 0s), 86.9 0s), 87.3 0s), 125.7 0d), 126.3 0d),
127.3 0d), 127.9 0d), 128.4 0d), 128.6 0d), 137.3 0s). MS m/z
0relative intensity); HRMS Calcd for CHO 0M)1, found.
1.1.11. Preparation of )6Z,4R and 4S,9S)-1-benzyloxy-9-
)tert-butyl-dimethyl-silanyloxy)-9-)2,2-dimethyl-1,3-
dioxolan-4-yl)-6-nonen-2-yn-4-ol )12) )RˆCH2OBn).
The sequence used above to obtain 7 from 6 was applied
to 11 on a 3.5 g 09.7 mmol) scale using the lithium salt of the
[02-propynyloxy)methyl]benzene, yielding 12 0RˆTMS)
03.6 g, 79% overall yield) as colourless oil: 1H NMR
0CDCl3) d 0.08 0s, 6H), 0.88 0s, 9H), 1.32 0s, 3H), 1.39 0s,
3H), 2.15 0s, 1H), 2.15±2.27 0m. 1H), 2.44±2.59 0m, 3H),
3.76±3.84 0m, 2H), 3.91±4.00 0m, 2H), 4.20 0s, 2H), 4.42±
4.51 0m, 1H), 4.59 0s, 2H), 5.58±5.73 0m, 2H); 13C NMR
0CDCl3) d 24.7 0q), 24.2 0q), 18.0 0s), 25.3 0q), 25.8 0q),
26.7 0q), 32.4 0t), 32.5 0t), 35.6 0t), 36.0 0t), 57.4 0t), 61.8 0d),
66.7 0t), 66.8 0t), 71.5 0t), 72.4 0d), 72.5 0d), 77.6 0d), 80.3
0s), 80.7 0s), 87.2 0s), 87.6 0s), 109.1 0s), 125.9 0d), 126.2 0d),
127.8 0d), 128.0 0d), 128.4 0d), 128.6 0d), 137.4 0s). MS m/z
0relative intensity); Anal. Calcd for C27H42O5Si: C, 68.31;
H, 8.92. Found: C, 68.32; H, 9.06.
1.1.15. Preparation of methyl)2E,4S,6Z,9R and 9S)-12-
Benzyloxy-4-)tert-butyl-dimethyl-silanyloxy)-9-hydroxy-
2,6-dodecadien-10-ynate )16). To a stirred solution of the
triol 15 0300 mg, 0.74 mmol) dissolved in THF/H2O 05:1,
7.4 mL) was added NaIO4 0652 mg, 3.05 mmol) and a
catalytic amount of tetra-n-butylammonium periodate at
rt. After 1 h, the mixture was ®ltered through a pad of Celite
and extracted with ether 02£10 mL) and washed with brine
020 mL). The resulting solution was concentrated, yielding
an oil of the crude aldehyde, which was used without
puri®cation.
1.1.12. Preparation of )1S,3Z,6R and 6S)-9-benzyloxy-1-
[)4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-nonen-7-yne-
1,6-diol )13) )RˆCH2OBn). The TBDPS-deprotection
used above to obtain 6 was applied to 12 0RˆCH2OBn)
compound on a 3 g 06.3 mmol) scale, yielding 13
0RˆCH2OBn) 02.0 g, 91% yield): 1H NMR 0CDCl3) d
1.33 0s, 3H), 1.40 0s, 3H), 2.25±2.30 0m, 2H), 2.30±2.46
0m, 1H), 2.46±2.56 0m, 1H), 3.64±3.72 0m, 1H), 3.92±4.00
0m, 4H), 4.18 0s, 2H), 4.44±4.60 0m, 1H), 4.66 0s, 2H),
5.63±5.71 0m, 2H); 13C NMR 0CDCl3) d 25.2 0q), 26.6
0q), 26.9 0q), 30.8 0t), 31.2 0t), 35.0 0t), 35.6 0t), 56.9 0t),
57.4 0t), 61.3 0d), 61.4 0d), 65.9 0t), 71.3 0d), 71.7 0t), 78.1
0d), 78.2 0d), 80.7 0s), 80.9 0s), 87.1 0s), 87.3 0s), 109.2 0s),
127.0 0d), 127.1 0d), 127.5 0d), 127.9 0d), 128.1 0d), 128.4
0d), 128.5 0d), 128.8 0d), 129.0 0d), 129.7 0s), 134.5 0s),
137.3 0s). MS m/z 0relative intensity); HRMS Calcd for
C13H15O3 0M2CH3)1, found.
To a suspension of sodium hydride 043 mg, 1.07 mmol, 60%
in mineral oil) in benzene 05 mL), at 08C was added slowly
trimethylphosphonoacetate 00.19 mL, 1.18 mmol) in
benzene 01 mL). After complete addition the mixture was
stirred for 5 min and the crude aldehyde dissolved in
benzene 02 mL) was added dropwise. The reaction mixture
was stirred for 30 min, after which time TLC showed
complete conversion to the unsaturated ester. The reaction
was quenched with saturated aqueous solution of NH4Cl
05 mL), extracted with ether 020 mL) and washed with

Â
D. D. Dõaz et al. / Tetrahedron 58 12002) 1913±1919
1919
2. 0a) Isolaurepinnacine from Laurencia pinnata Yamada:
Fukuzawa, A.; Masamune, T. Tetrahedron Lett. 1981, 22,
4081±4084. 0b) Rogioloxepanes A from L. microcladia:
Guella, G.; Mancini, I.; Chiasera, G.; Pietra, F. Helv. Chim.
Acta 1992, 75, 310±313. 0c) Neoisoprelaurefucin from L.
nipponica: Suzuki, M.; Takahashi, Y.; Matsuo, Y.; Masuda,
M. Phytochemistry 1996, 41, 1101. 0d) Neoisoprelaurefucin
from L. nipponica: Suzuki, M.; Mizumo, Y.; Matsuo, Y.;
Masuda, M. Phytochemistry 1996, 43, 121. 0e) Isoprelaurefu-
cin from L. nipponica: Kurosawa, E.; Fukuzawa, A.; Irie, T.
Tetrahedron Lett. 1973, 4135±4136. 0f) Isoprelaurefucin from
L. nipponica: Suzuki, M.; Kurta, K.; Suzuki, T.; Kurosawa, E.
Bull. Chem. Soc. Jpn 1986, 59, 2953±2957.
water 010 mL) and brine 010 mL), dried over MgSO4,
®ltered and concentrated. Flash-chromatography provided
a,b-unsaturated esters 16 0238 mg, 71% yield from the
1
triol): H NMR 0CDCl3) d 0.04 0s, 6H), 0.06 0bs, 6H),
0.91 0s, 9 H), 2.30±2.37 0m, 2H), 2.47 0t, Jˆ6.0 Hz, 2H),
3.73 0s, 3H), 4.20 0s, 2H), 4.33±4.37 0m, 1H), 4.43±4.47 0m,
1H), 4.59 0s, 2H), 5.57±5.69 0m, 2H), 6.00 0d, Jˆ15.5 Hz,
1H), 6.88±6.98 0m, 1H), 7.27±7.36 0m, 5H); 13C NMR
0CDCl3) d 18.2 0s), 25.8 0q), 35.6 0t), 35.7 0t), 35.8 0t),
51.5 0q), 57.4 0t), 61.8 0d), 71.3 0d), 71.6 0t), 80.9 0s), 87.0
0s), 119.7 0d), 126.5 0d), 126.6 0d), 127.8 0d), 128.0 0d),
128.3 0d), 128.4 0d), 137.4 0s), 150.5 0d), 167.0 0s). MS
m/z 0relative intensity); HRMS Calcd for CHO 0M)1, found.
3. 0a) Shimizu, Y. Chem. Rev. 1993, 93, 1685±1698.
0b) Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93, 1897±
1909.
1.1.16. Preparation of methyl)2E)-3-[)2S,7R)-7-)3-benzyl-
oxy-prop-1-ynyl)-3H,6H-oxepin-2-yl]-acrylate )17). The
sequence used above to obtain 14 from 12 was applied to
16 on a 220 mg 00.48 mmol) scale, yielding 17 as an oil
4. For additional methods to synthesize cyclic ethers, see:
Â
0a) Alvarez, E.; Candenas, M. L.; Perez, R.; Ravelo, J. L.;
Â
Martõn, J. D. Chem. Rev. 1995, 95, 1953±1980 and references
0114 mg, 73% overall yield): [a]25 ˆ213.0 0c 5.2,
D
1
CHCl3); H NMR 0CDCl3) d 2.31±2.43 0m, 2H), 2.49±
cited therein. 0b) Hoberg, J. O. Tetrahedron 1998, 54, 12631±
12670. 0c) Yet, L. Chem. Rev. 2000, 100, 2963±3007 and
references cited therein.
2.55 01H), 2.68±2.74 0m, 1H), 3.73 0s, 3H), 4.10 0br s, 1H),
4.18 0s, 2H), 4.30 0d, Jˆ7.7 Hz, 1H), 4.59 0s, 2H), 5.80 0br s,
2H), 6.13 0d, Jˆ11.8 Hz, 1H), 6.89 0dd, Jˆ11.7, 2.8 Hz, 1H),
7.29±7.41 0br s, 5H); 13C NMR 0CDCl3) d 36.6 0t), 38.6 0t),
51.5 0q), 57.3 0t), 70.3 0d), 71.6 0t), 78.7 0d), 80.3 0s), 85.8 0s),
120.4 0d), 127.8 0d), 128.4 0d), 129.2 0d), 129.3 0d), 129.6 0d),
137.4 0s), 147.5 0d), 166.9 0s). MS m/z 0relative intensity);
HRMS Calcd for CHO 0M)1, found.
 Â
5. 0a) Martõn, T.; Soler, M. A.; Betancort, J. M.; Martõn, V. S.
J. Org. Chem. 1997, 62, 1570±1571 and references cited
 Â
therein. 0b) Betancort, J. M.; Martõn, V. S.; Padron, J. M.;
 Â
Palazon, J. M.; Ramõrez, M. A.; Soler, M. A. J. Org. Chem.
Â
Â
1997, 62, 4570±4583. 0c) Ramõrez, M. A.; Padron, J. M.;
Â
Palazon, J. M.; Martõn, V. S. J. Org. Chem. 1997, 62, 4584±
Â
Â
4590. 0d) Martõn, T.; Martõn, V. S. Tetrahedron Lett. 2000, 41,
Â
 Â
2503±2505. 0e) Garcõa, C.; Soler, M. A.; Martõn, V. S.
Â
Tetrahedron Lett. 2000, 41, 4127±4130. 0f) Garcõa, C.;
Acknowledgements
Â
Â
Martõn, T.; Martõn, V. S. J. Org. Chem. 2001, 66, 1420±1428.
6. 0a) Nicholas, K. M. Acc. Chem. Res. 1987, 20, 207±214.
0b) Caffyn, A. J. M.; Nicholas, K. M. Comprehensive
Organometallic Chemistry-II; Hegedus, L. S., Ed.; Pergamon:
Oxford, 1995; Vol. 12, pp. 685±702 Chapter 7.1. 0c) Green,
J. R. Curr. Org. Chem. 2001, 5, 809±826.
We thank the DGES 0PB98-0443-C02-01) of Spain and
FEDER 01FD97-0747-C04-01) for supporting this research.
D. D. and J. M. B. thank the Spanish M.E.C. for a F.P.I.
fellowship. T. M. thanks the M.E.C. of Spain for a
Postdoctoral Reincorporation Contract.
Â
Â
7. Palazon, J. M.; Martõn, V. S. Tetrahedron Lett. 1995, 36, 3549.
8. Seyferth, D.; Nestle, M. O.; Wehman, A. T. J. Am. Chem. Soc.
1975, 97, 7417±7426.
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ences, see: Dõaz, D. D.; Martõn, V. S. Org. Lett. 2000, 2,
Â
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M. E.; Shaw, T. J. J. Am. Chem. Soc. 1980, 102, 6304±6311.
12. We had dif®culties to separate both diastereoisomers. At the
present time we cannot ensure which isomer is the predomi-
nant one.
13. We speculate about the in¯uence of the acetonide oxygens to
explain the different stereochemical behavior.
14. The best results were obtained by partial cleavage of the
acetonide 0ca. 50%) recycling the unreacted compound. A
prolonged acidic treatment produced a substantial amount of
the silyl-ether cleavage. See: Mikolajczyk, M.; Mikina, M.;
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