Syntheses of chiral dispiroacetals from carbohydrates

Article abstract of DOI:10.1021/jo972023a

The syntheses of trioxadispiroacetals from carbohydrates are described. (5R,7S,13R)-13-Methoxy-1,6,8-trioxadispiro[4.1.5.3]pentadecane (23) and (5S,7S,13R)-13-methoxy-1,6,8-trioxadispiro[4.1.5.3]-pentadecane (24) were prepared starting from D-galactose. The construction of the lateral tetrahydrofuran and tetrahydropyran rings was realized by homologation at C₁ and C₆ by appropriate tethers possessing a terminal primary alcohol. The cyclization of these alcohols at C₁ and C₅, respectively, was performed with (diacetoxyiodo)benzene and iodine in order to generate the alkoxy radicals which undergo an intramolecular hydrogen abstraction reaction. The diastereoisomers (5R,7S,13S)-13-methoxy-1,6,8- trioxadispiro[4.1.5.3]pentadecane (37) and (5S,7S,13S)-13-methoxyl-1,6,8- trioxadispiro[4.1.5.3]pentadecane (38) were prepared starting from tri-O- acetyl-D-glucal using a suitable methodology in which homologation and intramolecular hydrogen abstraction were again the key steps. We believe that this protocol could be easily extended to other tricyclic dispiroacetal ring systems.

Full text of DOI:10.1021/jo972023a

J . Org. Chem. 1998, 63, 2251-2261
2251
Syn th eses of Ch ir a l Disp ir oa ceta ls fr om Ca r boh yd r a tes
Rosa L. Dorta, Angeles Mart´ın, J ose´ A. Salazar, and Ernesto Sua´rez*
Instituto de Productos Naturales y Agrobiologı´a del C.S.I.C., Carretera de La Esperanza 3,
38206-La Laguna, Tenerife, Spain
Thierry Prange´
L.U.R.E. Universite´, Paris-Sud. Paris, 91405 ORSAY, Cedex, France
Received November 4, 1997
The syntheses of trioxadispiroacetals from carbohydrates are described. (5R,7S,13R)-13-Methoxy-
1,6,8-trioxadispiro[4.1.5.3]pentadecane (23) and (5S,7S,13R)-13-methoxy-1,6,8-trioxadispiro[4.1.5.3]-
pentadecane (24) were prepared starting from D-galactose. The construction of the lateral
tetrahydrofuran and tetrahydropyran rings was realized by homologation at C1 and C6 by
appropriate tethers possessing a terminal primary alcohol. The cyclization of these alcohols at C1
and C5, respectively, was performed with (diacetoxyiodo)benzene and iodine in order to generate
the alkoxy radicals which undergo an intramolecular hydrogen abstraction reaction. The diaste-
reoisomers (5R,7S,13S)-13-methoxy-1,6,8-trioxadispiro[4.1.5.3]pentadecane (37) and (5S,7S,13S)-
13-methoxy-1,6,8-trioxadispiro[4.1.5.3]pentadecane (38) were prepared starting from tri-O-acetyl-
D-glucal using a suitable methodology in which homologation and intramolecular hydrogen
abstraction were again the key steps. We believe that this protocol could be easily extended to
other tricyclic dispiroacetal ring systems.
The widespread occurrence of the substituted spiroac-
etal ring system as a substructure in a large range of
natural products has promoted considerable interest in
the development of synthetic routes to these compounds.1
Of special interest is the 1,6,8-trioxadispiro[4.1.5.3]-
pentadecane arrangement which appears in nature in a
small number of very important polyether ionophores
such as narasin,2 salinomycin3 and noboritomycin4 and
the antibiotics CP 44,6615 and X 14766A.6 Recently,
other molecular systems containing dispiro arrangements
of the 1,7,9-trioxadispiro[5.1.5.2]pentadecane7 and 1,6,8-
trioxadispiro[4.1.5.2]tetradecane8 types have been iso-
lated from marine organisms. To study the configuration
and conformation of the system, some other simpler
models of trioxadispiroacetals have also been prepared
and in a few cases X-ray crystallographic analysis has
been used.9
We have recently reported on a method for the syn-
thesis of optically active bicyclic spiroacetals from car-
bohydrates in which the spirocenter is achieved by an
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Grenier-Laustalot, M. F.; Metras, F.; Cottier, L.; Descotes, G. Spectrosc.
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Am. Chem. Soc. 1990, 112, 6389.
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61, 3999. For different approaches to spiroacetals from carbohydrates,
see: (b) Cubero, I. I.; Lo´pez Espinosa, M. T. P.; Richardson, A. C.;
Aamlid, K. H. Carbohydr. Res. 1993, 242, 281. (c) Cubero, I. I.; Lo´pez
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S0022-3263(97)02023-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 03/06/1998

2252 J . Org. Chem., Vol. 63, No. 7, 1998
Dorta et al.
Sch em e 1
Sch em e 2a
a
Key: (a) AcOH (80%), 50 °C, 4 h, 80%; (b) 1,1′-thiocarbonyl-
diimidazole, MeCN, rt, 5 h 90%; (c) trimethyl phosphite, reflux,
4.5 h, 80%; (d) Pd(OH)2/C, H2, EtOH, 5 h, 85%; (e) K2CO3, MeOH,
rt, 3 h, 100%; (f) TBDPSCl, imidazole, DMF, rt, 5 min, 79%; (g)
dimethyl sulfate, NaOH, acetone, 45 °C f reflux, 2 h, 87%; (h)
BCl3‚SMe2, CH2Cl2, rt, 14 h, 74%.
intramolecular hydrogen abstraction (IHA) reaction pro-
moted by alkoxy radicals.10a We wish to report here on
an extension of this methodology to the synthesis of
tricyclic dispiroacetals of the 1,6,8-trioxadispiro[4.1.5.3]-
pentadecane type from carbohydrates.11
As shown in Scheme 1, the construction of the terminal
tetrahydropyran ring on the anomeric center via C-
glycosylation and an IHA reaction from the appropriate
alcohol would give intermediate A. Two-carbon homolo-
gation of the C5 tether and a second IHA reaction would
afford tricyclic dispiroacetal C. If we change the position
of the lateral heterocyclic rings and introduce the tet-
rahydropyran ring at C5 and the tetrahydrofuran at C1,
we can obtain the tricyclic dispiroacetal D via intermedi-
ate B.
This methodology would allow us the preparation of
both enantiomeric dispiroacetals from the same carbo-
hydrate in an enantiodivergent synthesis with the sole
condition that the groups at C2 and C4 (R1 and R3) are
enantiomorphic, as is the case when D-glucose (R1 ) R2
) R3 ) OH) is used as starting material.
Using this protocol and in order to devise simpler
models, we have prepared two tricyclic dispiroacetals C
(R1 ) OMe, R2 ) R3 ) H) and D (R1 ) R2 ) H, R3 ) OMe)
starting from two appropriate dideoxysugars.
acetylation of these alcohols gave compound 1. Acetic
acid hydrolysis of the acetonide gave the corresponding
diol 2 which was transformed into the cyclic thionocar-
bonate 3, in 90% yield14 (Scheme 2). A small amount
(10%) of the 3,4-dithionoimidazole derivative 4 was also
obtained. Reduction with trimethyl phosphite produced
olefin 5 in 80% yield.15 Hydrogenation of the double bond
was accomplished using Pd(OH)2/C as catalyst to give 6
in 85% yield. Hydrogenolysis of the benzyl ether at C1
was not observed under these conditions, but a very small
amount (2%) of the 2-deoxy compound was found in the
reaction mixture. Deprotection of the C2 and C6 hydroxyl
groups was followed by selective protection of the primary
alcohol with tBuPh2SiCl to give 8 in 79% yield. O-
Methylation of the alcohol at C2 provided 9 which
underwent selective cleavage of the anomeric benzyl
ether when submitted to the BCl3‚SMe2 complex.16 This
alternative procedure was necessary since, as commented
previously, the anomeric benzyl ether was inert under
the more usual hydrogenolytic cleavage over Pd/C or Pd-
(OH)2/C.
The resulting anomeric mixture 10 was transformed
into the glycosyl chloride17 and alkylated with 4-pente-
nylmagnesium bromide yielding the C-glycosides 11 and
12 as a (â:R, 1:3.7) mixture that was separated by
chromatography (Scheme 3).18 The stereochemistry at
C1 was determined by careful analysis of the correspond-
ing coupling constants of the ddd systems at C2. The
alcohols 13 and 14 were obtained by ozonolysis followed
by in situ reduction with NaBH4. The intramolecular
hydrogen abstraction reaction was then carried out by
treating 13 with the (diacetoxyiodo)benzene (DIB)/iodine
system to yield the spiroacetal isomers 15 and 16. The
Resu lts a n d Discu ssion
In our first synthesis, we decided to prepare the key
intermediate 10 for the construction of the right-hand
tetrahydropyran ring via C-glycosidation. We chose
benzyl R-D-galactopyranoside12 as our starting material
because its structure allows the selective protection of
the C3 and C4 hydroxyl groups as an isopropylidene while
leaving the C2 and C6 hydroxyl groups unprotected.13 The
(14) Groneberg, R. D.; Miyazaki, T.; Stylianides, N. A.; Schulze, T.
J .; Stahl, W.; Schreiner, E. P.; Suzuki, T.; Iwabuchi, Y.; Smith, A. L.;
Nicolaou, K. C. J . Am. Chem. Soc. 1993, 115, 7593.
(15) Corey, E. J .; Winter, R. A. E. J . Am. Chem. Soc. 1963, 85, 2677.
(16) Congreve, M. S.; Davison, E. C.; Fuhry, M. A. M.; Holmes, A.
B.; Payne, A. N.; Robinson, R. A.; Ward, S. E. Synlett 1993, 663.
(17) Lee, J . B.; Nolan, T. J . Tetrahedron 1967, 23, 2789.
(18) Franc¸ois, P.; Perilleux, D.; Kempener, Y.; Sonveaux, E. Tetra-
hedron Lett. 1990, 31, 6347.
(11) For preliminary communications, see: (a) Dorta, R. L.; Martı´n,
A.; Sua´rez, E.; Prange´, T. Tetrahedron: Asymmetry 1996, 7, 1907. (b)
Dorta, R. L.; Mart´ın, A.; Salazar, J . A.; Sua´rez, E.; Prange´, T.
Tetrahedron Lett. 1996, 37, 6021.
(12) Sato, K.; Yoshitomo, A. Chem. Lett. 1995, 39.
(13) (a) Lipta´k, A.; Fu¨gedi, P.; Kere´kgya´rto´, J .; Na´na´si, P. Carbo-
hydr. Res. 1983, 113, 225. (b) Barili, P. L.; Berti, G.; Catelani, G.;
Colonna, F.; Marra, A. Tetrahedron Lett. 1986, 27, 2307.

Chiral Dispiroacetals from Carbohydrates
J . Org. Chem., Vol. 63, No. 7, 1998 2253
Sch em e 3a
Sch em e 4a
a
Key: (a) TsCl, Py, rt, 15 h, 100%; (b) CH2dCHCH2MgBr, Et2O,
rt, 2 h, 85%; (c) O3, CH2Cl2/MeOH, -78 °C, then NaBH4, rt, 3 h,
98%; (d) DIB, I2, cyclohexane, hν, rt, 4 h, 56%.
possibility is that a hydrogen abstraction has taken place
at C1′ of 14 through a six-membered cyclic transition
state. The loss of a hydrogen atom would give a 1,1′-
olefin which upon 6-endo-trig iodocyclofunctionalization
would yield the observed iodine compounds. Neverthe-
less, the possibility of a double hydrogen abstraction
cannot be totally discarded. In any case, these mecha-
nisms do not explain why the iodine compounds are only
observed during the IHA reaction of diastereoisomer 14.
Attempts to calculate the energy of the possible transition
states by using a MM2 force field model does not throw
any light either.22
a
Key: (a) (1) Ph3P, CCl4, THF, reflux, 3 h, (2) CH2dCH-
(CH2)3MgBr, Et2O, 0 °C, 1 h, 74%; (b) O3, CH2Cl2/MeOH, -78 °C,
then NaBH4, rt, 4 h, 95%; (c) DIB, I2, cyclohexane, hν, 40 °C, 70
min; (d) HCl, AcOH, rt, 2 h, 100%; (e) nBu3SnH, AIBN, PhH, reflux,
35 min.
reaction proceeded in good yield (87%, 16:15, 1:1.4), the
minor isomer 16 being thermodynamically less stable,
as indicated by the acid-catalyzed quantitative isomer-
ization of 16 to 15.
Deprotection and subsequent tosylation of compound
15 afforded tosylate 20, which, as shown in Scheme 4,
was subjected to the reaction with allylmagnesium
bromide to afford olefin 21 in 85% yield. Ozonolysis
followed by a reductive workup yielded alcohol 22, which
was submitted to a second hydrogen abstraction reaction
with DIB/iodine to give a mixture of the 1,6,8-trioxadispiro-
[4.1.5.3]pentadecane derivatives 23 and 24 in a ratio of
1:1.4. The stereochemistries at C5 and C7 were clearly
assigned on the basis of the ROESY spectra (principal
correlations shown by arrows in Scheme 4). The minor
compound 23 is the thermodynamically more stable (by
4.1 kcal/mol),21 the stereochemistries of the chiral centers
being established as 5R,7S,13R for 23 and 5S,7S,13R for
its C5 isomer 24. Unfortunately, attempts at acid-
catalyzed equilibration of 24 were unsuccessful. The
molecule seems to be very sensitive to these conditions,
and a chroman derivative, formed by an intramolecular
aldolic reaction, was the only isolated product.23
The second synthesis began as outlined in Scheme 5.
The starting material chosen was the known compound
25, prepared from tri-O-acetyl-D-glucal using a previously
reported methodology.24 Hydrogenation and deprotection
of the acetonide cleanly gave the corresponding diol 27
in 70% overall yield, which was transformed into com-
pound 28 by selective tosylation of the primary hydroxyl
group. Alkylation of tosylate 28 with allylmagnesium
The stereochemistry of the spirocenter of this dioxaspiro-
[5.5]undecanyl ring system was confirmed by X-ray
crystallographic analysis of compound 15.19 As expected,
the preferred conformation of the rings is determined
principally by the maximum number of anomeric ef-
fects.20 A study by molecular mechaniscs using the MMX
force field21 is in accord with the stability observed for
the pair of stereoisomers obtained, 15 being favored over
16 by 3.9 kcal/mol of MMX steric energy.
Interestingly, when the hydrogen abstraction reaction
was performed with the isomeric alcohol 14, a pair of
isomeric iodine compounds 17 and 18 was obtained,
although in low yield (15%), apart from the expected
spiroacetals 15 and 16 (51%). Both iodine compounds
were reduced with nBu3SnH/AIBN to the same spiroac-
etal 15 in good yield, indicating an identical stereochem-
istry at the spirocenter. The position and configuration
1
of the iodine atoms were established by H NMR spec-
troscopy, the chemical shifts and coupling constants being
in accord with the axial and equatorial orientation
proposed for 17 and 18, respectively. Although the
formation of these iodine compounds is unclear, one
(19) The author has deposited the atomic coordinates for this
structure with the Cambridge Crystallographic Data Centre. The
coordinates can be obtained, upon request, from the Director, Cam-
bridge Cystallographic Data Centre, 12 Union Road, Cambridge, CB2
1EZ, U.K.
(20) (a) Deslongchamps, P. Stereoelectronic Effects in Organic
Chemistry; Pergamon Press: New York, 1983. (b) Deslongchamps, P.;
Rowan, D. D.; Pothier, N.; Sauve´, T.; Saunders: J . K. Can. J . Chem.
1981, 59, 1105. (c) Pothier, N.; Rowan, D. D.; Deslongchamps, P.;
Saunders: J . K. Can. J . Chem. 1981, 59, 1132.
(21) MMX force field as implemented in PCMODEL (v. 4.0), Serena
Software, Bloomington, IN 47402-3076. See: Gajewski, J . J .; Gilbert,
K. E.; McKelvey, J . Advances in Molecular Modelling; J AI Press:
Greenwich, CT, 1992; Vol. 2.
(22) (a) Dorigo, A. E.; Houk, K. N. J . Org. Chem. 1988, 53, 1650. (b)
Dorigo, A. E.; McCarrick, M. A.; Loncharich, R. J .; Houk, K. N. J . Am.
Chem. Soc. 1990, 112, 7508.
(23) Dorta, R. L.; Mart´ın, A.; Sua´rez, E.; Betancor, C. J . Org. Chem.
1997, 62, 2273.
(24) Danishefsky, S.; Kerwin, J . F., J r. J . Org. Chem. 1982, 47, 3803.
Nicolaou, K. C.; Duggan, M. E.; Hwang, C.-K. J . Am. Chem. Soc. 1989,
111, 6666.

2254 J . Org. Chem., Vol. 63, No. 7, 1998
Dorta et al.
Sch em e 5a
Sch em e 7a
a
Key: (a) Pd(OH)2/C, H2, EtOAc, 80%; (b) Amberlyst-15 (H+),
MeOH, rt, 1 h, 88%; (c) TsCl, Py, 0 °C, 4 h, 88%; (d) CH2dCH-
CH2MgBr, Et2O, 0 °C, 3 h, 80%; (e) dimethyl sulfate, NaOH,
acetone, 50 °C, 4 h, 73%; (f) BH3‚THF, THF, 0 °C, 1 h, 73%; (g)
TBAF, THF, rt, 2 h, 95%.
Sch em e 6a
a
Key: (a) DIB, I2, CCl4, rt, 90 min, 43%; (b) TBAF, THF, rt, 2
h, 86%; (c) p-nitrobenzoyl choride, Py/CH2Cl2, rt, 14 h, 97%; (d)
DIB, I2, cyclohexane, rt, 140 min, 78%.
from the conformation 1C4 that avoids the 1,3-diaxial
interactions between the hydrogen at C5 and the side
chain at C1. Furthermore, the calculated energy22 of the
1
seven-membered transition state for the conformation C4
is approximately 1 kcal/mol lower than the corresponding
energy of the transition state for the abstraction reaction
in the conformation C1. The structure and stereochem-
a
Key: (a) DIB, I2, cyclohexane, rt, 30 min, 60%.
4
bromide elongated the side chain at C6 by a three-carbon
unit necessary for the construction of the tetrahydropy-
ran ring. O-Methylation of the secondary alcohol 29 with
dimethyl sulfate/NaOH afforded methyl ether 30 in 73%
yield. Hydroboration of the terminal olefin 30 with
BH3‚THF followed by oxidative workup furnished the key
intermediate alcohol 31 which was desilylated with TBAF
to give diol 32. This molecule contains the numbers of
carbons and convenient functionality for subsequent
elaboration of the trioxadispiro compound. Unfortu-
nately, attempts to elaborate the trioxadispiro system
directly from diol 32 by simultaneous double hydrogen
abstraction reaction were unsuccessful and produced the
dioxaspiro[4.5]decane ring system derivative 33 as the
sole reaction product (Scheme 6). As expected, the
tetrahydrofuran ring was formed first and the 1,3-diaxial
interaction with the group at C1 seemed to hinder the
radical abstraction of the C5 hydrogen through a less-
favored seven-membered cyclic transition state.10a
istry of spiro 34 were deduced from its spectroscopic data,
COSY, TOCSY, HMBC, and HMQC experiments, and
confirmed by X-ray crystallographic analysis of a crystal-
line p-nitrobenzoate ester derivative 36.19 Both rings
adopt a chair conformation with a maximum number of
anomeric effects, leaving the methoxy group in the axial
orientation.
Treatment of silyl ether derivative 34 with TBAF gave
rise to alcohol 35, which underwent intramolecular
hydrogen abstraction to give the desired trioxadispiroac-
etals 37 and 38 in 78% yield. These compounds, as in
the case of the other trioxadispiro prepared above, are
also highly sensitive to traces of acid, and it was neces-
sary to isolate them very carefully. The 1H NMR
spectrum of 37 showed a proton at δ 3.22 as a triplet of
J ) 2.9 Hz, indicating the axial disposition for the
methoxyl group at C13, and a strong deshielding for the
axial proton at C14 (δ 2.67) owing to the 1.3-diaxial
interactions with the oxygen atoms of the two adjacent
rings.9c,g This confirmed that the central ring adopted
the same chair conformation as that of its precursor
alcohol, the stereochemistry of the chiral centers being
established as 5R,7S,13S.
Scheme 7 outlines a more efficient strategy involving
first the formation of the dioxadispiro[5.5]undecane ring
system. This was accomplished by reaction of alcohol 31
with the DIB/iodine reagent which gave compound 34 as
the sole product in 43% yield. The presence of a triplet
at δ 2.92 (J ) 2.5 Hz) clearly indicated an axial disposi-
tion of the methoxyl group at C13. A study by molecular
mechanics indicated that the steric energy for both chair
For compound 38, we observed that the proton at C13
appears as a double doublet at δ 3.12 (J ) 3.9, 9.5 Hz),
indicating an equatorial orientation for the methoxyl
group. The ROESY spectrum showed a spatial con-
nectivity between H12 and H14 revealing the preference
for this compound to exist in the conformation 4C1 for
4
conformers of 31 (1C4 and C1) is similar (∆ ) 0.09 kcal/
mol) allowing an equilibrium between them, the hydro-
gen abstraction and subsequent cyclization occurring

Chiral Dispiroacetals from Carbohydrates
J . Org. Chem., Vol. 63, No. 7, 1998 2255
22), 303 (2), 287 (38), 245 (16), 228 (49), 215 (100), 174 (24),
157 (62). Anal. Calcd for C20H26O8: C, 60.90; H, 6.64.
Found: C, 61.02; H, 6.30.
the central ring with two anomeric effects and the
methoxyl group in equatorial position. The other con-
formation, 1C4, with the same number of anomeric effects
but with an axial methoxyl group, is less favored by 1.6
kcal/mol as determined by molecular mechanics. Com-
pound 38 is then a C5 epimer of 37, and its stereochem-
istry is consequently 5S,7S,13S.
In conclusion, we have prepared four of eight possible
isomers of the target molecule demonstrating the useful-
ness of a double IHA reaction to construct the lateral
heterocyclic rings in this type of compounds. Despite the
fact that the acid-sensitive nature of the models pre-
cluded the equilibration of the acetalic centers and, hence,
the synthesis of the pair of enantiomers proposed, this
methodology is particularly convenient when a specific
stereochemistry is required at the spirocenters, since
thermodynamically less stable isomers can also be ob-
tained.
Ben zyl 2,6-Di-O-a cetyl-r-D-ga la ctop yr a n osid e (2).
A
solution of compound 1 (2.42 g, 6.1 mmol) in AcOH (80%, 170
mL) was stirred at 50 °C for 4 h and then concentrated under
reduced pressure. Dry column chromatography of the residue
(hexanes-EtOAc, 35:65) gave the title compound 2 (1.75 g,
4.94 mmol, 80%): mp 132.5-133.9 °C (from acetone-n-
hexane); [R]D +181.4° (c ) 0.290); IR 3565, 1736, 1236 cm-1
;
1H NMR 2.10 (3H, s), 2.11 (3H, s), 3.00 (2H, br s), 3.97-4.10
(3H, m), 4.20 (1H, dd, J ) 6.6, 11.3 Hz), 4.40 (1H, dd, J ) 5.9,
11.3 Hz), 4.53 (1H, d, J ) 12.1 Hz), 4.72 (1H, d, J ) 12.1 Hz),
5.01 (1H, dd, J ) 3.8, 10.0 Hz), 5.09 (1H, d, J ) 3.8 Hz), 7.32-
7.36 (5H, m); 13C NMR 20.80 (q), 20.89 (q), 63.18 (t), 67.98 (2
× d), 69.41 (d), 69.56 (t), 71.36 (d), 95.53 (d), 127.76 (2 × d),
127.92 (d), 128.41 (2 × d), 137.04 (s), 171.11 (s), 171.44 (s);
MS (EI) m/z (rel intensity) 337 ([M - OH]+, 1), 287 (7), 263
(29), 229 (5), 203 (22), 187 (33), 169 (31), 91 (100). Anal. Calcd
for C17H22O8: C, 57.62; H, 6.26. Found: C, 57.59; H, 5.94.
Ben zyl 2,6-Di-O-a cetyl-3,4-O-th ioca r bon yl-r-D-ga la c-
top yr a n osid e (3). To a solution of diol 2 (1.71 g, 4.83 mmol)
in dry acetonitrile (28 mL) was added under nitrogen 1,1′-
thiocarbonyldiimidazole (2.58 g, 14.5 mmol), and the solution
was stirred at room temperature for 5 h. The reaction mixture
was then poured into brine and extracted with CHCl3. The
organic extracts were dried over Na2SO4 and concentrated
under reduced pressure. Dry column chromatography of the
residue (hexanes-EtOAc, 75:25 f 35:65) gave compound 3
(1.72 g, 4.34 mmol, 90%) and benzyl 2,6-di-O-acetyl-3,4-di-O-
(1′H-imidazol-1′-ylthiocarbonyl)-R-D-galactopyranoside (4) (280
mg, 0.488 mmol, 10%). Compound 3: [R]D +123.1° (c ) 0.316);
Exp er im en ta l Section
Gen er a l. Melting points were determined with a hot-stage
apparatus and are uncorrected. Optical rotation measure-
ments were recorded at room temperature in CHCl3. IR
spectra were recorded in CHCl3 solutions unless otherwise
stated. NMR spectra were determined at 200, 400, or 500
MHz for H and 50.3 or 100.6 MHz for 13C for CDCl3 solutions
1
unless otherwise stated in the presence of TMS as internal
standard. Phase-sensitive ROESY spectra were measured
with a mixing time of 700 ms. Mass spectra were determined
at 70 eV unless otherwise specified. Merck silica gel 60 PF254
and 60 (0.063-0.2 mm) were used for preparative thin-layer
chromatography (TLC) and column chromatography, respec-
tively, unless otherwise stated. Circular layers of 1 mm of
Merck silica gel 60 PF254 were used on a Chromatotron for
centrifugally assisted chromatography. Commercial reagents
and solvents were analytical grade or were purified by
standard procedures prior to use.25 All reactions involving air-
or moisture-sensitive materials were carried out under a
nitrogen atmosphere. The spray reagent for TLC was vanillin
(1 g) in H2SO4-EtOH (4:1; 200 mL). (Diacetoxyiodo)benzene
(DIB) 98% was purchased from Aldrich.
1
IR 1748, 1231, 1134 cm-1; H NMR 2.08 (3H, s), 2.11 (3H, s),
4.29-4.41 (3H, m), 4.54 (1H, d, J ) 12.0 Hz), 4.71 (1H, d, J )
12.0 Hz), 4.96 (1H, dd, J ) 4.1, 7.2 Hz), 4.97 (1H, dd, J ) 1.7,
7.0 Hz), 5.11 (1H, t, J ) 7.1 Hz), 5.18 (1H, d, J ) 4.0 Hz),
7.29-7.37 (5H, m); 13C NMR 20.48 (q), 20.65 (q), 61.93 (t),
64.26 (d), 68.84 (d), 70.33 (t), 78.08 (d), 78.85 (d), 93.95 (d),
127.81 (2 × d), 128.32 (d), 128.54 (2 × d), 135.97 (s), 169.44
(s), 170.23 (s), 189.80 (s); MS (EI) m/z (rel intensity) 397 ([M
+ H]+, 3), 305 (1), 289 (4), 263 (3), 230 (2), 187 (3), 139 (19),
107 (21), 91 (100). Anal. Calcd for C18H20O8S: C, 54.53; H,
5.09; S, 8.07. Found: C, 54.81; H, 5.24; S, 8.03. Compound
4: IR 1748, 1395, 1288, 1240 cm-1; 1H NMR 2.02 (3H, s), 2.03
(3H, s), 4.15 (2H, d, J ) 6.7 Hz), 4.54 (1H, t, J ) 6.5 Hz), 4.67
(1H, d, J ) 12.2 Hz), 4.83 (1H, d, J ) 12.2 Hz), 5.31 (1H, d, J
) 3.7 Hz), 5.45 (1H, dd, J ) 3.8, 10.7 Hz), 6.26 (1H, dd, J )
3.3, 10.7 Hz), 6.60 (1H, d, J ) 3.1 Hz), 6.97 (1H, d, J ) 2.0
Hz), 7.11 (1H, d, J ) 2.0 Hz), 7.34 (1H, t, J ) 1.5 Hz), 7.38-
7.41 (5H, m), 7.62 (1H, t, J ) 1.4 Hz), 8.17 (1H, s), 8.35 (1H,
s); 13C NMR 20.47 (q), 20.52 (q), 61.27 (t), 66.46 (d), 67.52 (d),
70.32 (t), 75.90 (d), 76.03 (d), 95.36 (d), 117.29 (d), 117.71 (d),
127.98 (2 × d), 128.34 (d), 128.55 (2 × d), 131.15 (d), 131.51
(d), 136.03 (s), 136.98 (d), 137.05 (d), 169.86 (s), 170.01 (s),
182.35 (s), 183.08 (s).
Ben zyl 2,6-Di-O-a cetyl-3,4-O-isop r op ylid en e-r-D-ga la c-
top yr a n osid e (1). To a solution of compound benzyl R-D-
galactopyranoside (3.1 g, 11.5 mmol) in dry acetone (94 mL)
were added, under nitrogen at 0 °C, 2,2-dimethoxypropane
(4.24 mL, 34.5 mmol) and TsOH (200 mg, 1.15 mmol), and the
solution was stirred for 7 h at this temperature. The reaction
mixture was allowed to warm to room temperature and treated
with triethylamine (2.6 mL, 18.4 mmol) and pyridine (30 mL).
The solution was stirred for a further 15 min and concentrated
under reduced pressure. The residue was dissolved in dry
pyridine (30 mL), acetic anhydride (15 mL) was added, and
the solution was stirred at room temperature for 20 h. Water
was then added and the mixture extracted with CH2Cl2. The
combined extracts were washed with dilute HCl (10%), satu-
rated solution of NaHCO3, and water, dried over Na2SO4, and
concentrated under reduced pressure. Dry column chroma-
tography of the residue (hexanes-EtOAc, 80:20) gave the title
compound 1 (2.5 g, 6.34 mmol, 56%): mp 95.5-96.7 °C (from
acetone-n-hexane); [R]D +177.6° (c ) 0.500); IR 1740, 1370,
Ben zyl 2,6-Di-O-a cetyl-3,4-d id eoxy-r-D-er yth r o-h ex-3-
en op yr a n osid e (5). A solution of compound 3 (1.63 g, 4.12
mmol) in trimethyl phosphite (100 mL) was heated at reflux
temperature for 4.5 h. The reaction mixture was then
concentrated under high vacuum (1 mmHg), and the residue
was purified by dry column chromatography (hexanes-EtOAc,
85:15) to give the title compound 5 (1.05 g, 3.28 mmol, 80%):
1
IR 1736, 1372, 1228 cm-1; H NMR 2.08 (3H, s), 2.10 (3H, s),
1240 cm-1 1H NMR 1.33 (3H, s), 1.51 (3H, s), 2.08 (3H, s),
;
4.17 (2H, d, J ) 5.0 Hz), 4.41 (1H, m), 4.65 (1H, d, J ) 12.3
Hz), 4.80 (1H, d, J ) 12.3 Hz), 5.27 (1H, dd, J ) 0.8, 4.3 Hz),
5.31 (1H, dddd, J ) 1.7, 1.7, 3.5, 4.3 Hz), 5.75 (1H, dddd, J )
1.6, 1.6, 1.6, 10.6 Hz), 5.85 (1H, ddd, J ) 1.4, 1.8, 10.6 Hz),
7.29-7.36 (5H, m); 13C NMR 20.81 (2 × q), 65.24 (t), 66.26
(d), 67.06 (d), 70.12 (t), 93.88 (d), 124.34 (d), 127.79 (d), 127.87
(d), 127.92 (2 × d), 128.35 (2 × d), 137.27 (s), 170.31 (s), 170.73
(s); MS (EI) m/z (rel intensity) 247 ([M - CH3COOCH2]+, 4),
229 (2), 213 (34), 184 (100), 169 (19), 142 (100), 108 (77), 91
(98). Anal. Calcd for C17H20O6: C, 63.72; H, 6.30. Found: C,
63.82; H, 6.64.
2.11 (3H, s), 4.22-4.28 (2H, m), 4.32-4.42 (3H, m), 4.51 (1H,
d, J ) 12.1 Hz), 4.71 (1H, d, J ) 12.1 Hz), 4.91 (1H, dd, J )
3.7, 8.0 Hz), 5.03 (1H, d, J ) 3.7 Hz), 7.30-7.33 (5H, m); 13C
NMR 20.84 (2 × q), 26.26 (q), 27.79 (q), 63.55 (t), 65.86 (d),
69.54 (t), 71.55 (d), 73.25 (d), 73.34 (d), 95.06 (d), 109.91 (s),
127.69 (2 × d), 127.95 (d), 128.41 (2 × d), 136.83 (s), 170.35
(s), 170.68 (s); MS (EI) m/z (rel intensity) 379 ([M - CH3]+,
(25) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon Press: New York, 1988.

2256 J . Org. Chem., Vol. 63, No. 7, 1998
Dorta et al.
Ben zyl 2,6-Di-O-a cet yl-3,4-d id eoxy-r-D-er yth r o-h ex-
op yr a n osid e (6). A suspension of 5 (100 mg, 0.312 mmol)
and 20% Pd(OH)2 on charcoal (40 mg) in EtOH (10 mL) was
1.08 (9H, s), 1.37-1.51 (1H, m), 1.64-1.97 (4H, m), 3.58 (1H,
dd, J ) 5.0, 10.3 Hz), 3.68 (1H, m), 3.71 (1H, dd, J ) 5.8, 10.3
Hz), 3.86 (1H, dddd, J ) 1.7, 5.4, 5.4, 11.0 Hz), 4.54 (1H, d, J
) 11.7 Hz), 4.82 (1H, d, J ) 11.7 Hz), 4.91 (1H, d, J ) 3.5 Hz),
7.33-7.48 (11H, m), 7.67-7.74 (4H, m); 13C NMR 19.24 (s),
26.81 (3 × q), 26.81 (t), 27.34 (t), 66.62 (t), 68.23 (d), 68.77 (t),
69.27 (d), 97.27 (d), 127.62 (4 × d), 127.78 (d), 127.98 (2 × d),
128.43 (2 × d), 129.63 (2 × d), 133.55 (2 × s), 135.60 (4 × d),
137.63 (s); MS (EI) m/z (rel intensity) 401 ([M - tBu - H2O]+,
1), 311 (32), 291 (4), 251 (15), 233 (43), 207 (14), 91 (100). Anal.
Calcd for C29H36O4Si: C, 73.07; H, 7.61. Found: C, 73.23; H,
7.73.
Ben zyl 6-O-(ter t-Bu tyld ip h en ylsilyl)-3,4-d id eoxy-2-O-
m eth yl-r-D-er yth r o-h exop yr a n osid e (9). To a solution of
alcohol 8 (1.62 g, 3.40 mmol) in dry acetone (44 mL) was added,
under nitrogen, pulverized NaOH (1.24 g, 0.031 mol). The
reaction mixture was heated at 45 °C, and dimethyl sulfate
(1.61 mL, 0.017 mol) was added dropwise. The solution was
heated at reflux temperature for 2 h, poured into 10% aqueous
solution of HCl, and extracted with CH2Cl2. The organic
extracts were washed with brine, dried over Na2SO4, and
concentrated under reduced pressure. The residue was puri-
fied by column chromatography (hexanes-EtOAc, 95:5) to give
the title compound 9 (1.45 g, 2.96 mmol, 87%): [R]D +58° (c )
0.238); IR 3071, 2932, 2830, 1105 cm-1; 1H NMR 1.11 (9H, s),
1.32-1.53 (1H, m), 1.70-1.97 (3H, m), 3.34 (1H, m), 3.34 (3H,
s), 3.59 (1H, dd, J ) 4.9, 10.4 Hz), 3.70 (1H, dd, J ) 5.8, 10.4
Hz), 3.91 (1H, dddd, J ) 2.1, 5.4, 5.4, 11.5 Hz), 4.64 (1H, d, J
) 12.2 Hz), 4.83 (1H, d, J ) 12.2 Hz), 4.99 (1H, d, J ) 3.3 Hz),
7.29-7.50 (11H, m), 7.70-7.76 (4H, m); 13C NMR 19.23 (s),
23.30 (t), 26.81 (3 × q), 26.81 (t), 56.24 (q), 66.67 (t), 68.10 (t),
69.18 (d), 77.27 (d), 94.54 (d), 127.52 (d), 127.60 (4 × d), 128.12
(2 × d), 128.24 (2 × d), 129.60 (2 × d), 133.57 (2 × s), 135.61
(4 × d), 137.75 (s); MS (EI) m/z (rel intensity) 433 ([M - tBu]+,
3), 401 (5), 355 (3), 325 (78), 297 (14), 265 (19), 239 (28), 233
(76), 91 (100). Anal. Calcd for C30H38O4Si: C, 73.43; H, 7.81.
Found: C, 73.37; H, 7.95.
stirred at room temperature for 5 h under
a hydrogen
atmosphere. After the catalyst was filtered off, the solvent
was removed under reduced pressure. Chromatotron chro-
matography (hexanes-EtOAc, 90:10) of the residue gave
compound 6 (86 mg, 0.267 mmol, 85%) and benzyl 6-O-acetyl-
2,3,4-trideoxy-R-D-glycero-hexopyranoside (2 mg, 0.007 mmol,
2%): [R]D +92.4° (c ) 0.840); IR 1732, 1240, 1023 cm-1 1H
;
NMR 1.33-2.08 (6H, m), 2.10 (3H, s), 4.06 (1H, m), 4.07 (2H,
d, J ) 1.6 Hz), 4.49 (1H, d, J ) 11.8 Hz), 4.73 (1H, d, J ) 11.8
Hz), 4.96 (1H, br s), 7.28-7.37 (5H, m); 13C NMR 17.56 (t),
20.81 (q), 28.96 (t), 29.27 (t), 66.94 (d), 67.13 (t), 68.46 (t), 96.42
(d), 127.49 (d), 127.77 (2 × d), 128.30 (2 × d), 138.10 (s), 170.87
(s). MS (EI) m/z (rel intensity) 265 ([M + H]+, 3), 264 (M+, 1),
191 (5), 181 (11), 173 (8), 157 (100), 137 (37), 113 (25), 97 (100).
Anal. Calcd for C15H20O4: C, 68.16; H, 7.63. Found: C, 68.24;
H, 7.80. Compound 6: [R]D +138.7° (c ) 0.380); IR 1738, 1232,
1045 cm-1; 1H NMR 1.54-2.12 (4H, m), 2.05 (3H, s), 2.09 (3H,
s), 4.03 (1H, m), 4.06 (2H, s), 4.57 (1H, d, J ) 12.3 Hz), 4.77
(1H, d, J ) 12.3 Hz), 4.79 (1H, ddd, J ) 3.5, 5.0, 11.6 Hz),
4.98 (1H, d, J ) 3.4 Hz), 7.30-7.37 (5H, m); 13C NMR 20.72
(q), 20.90 (q), 22.70 (t), 26.31 (t), 66.02 (t), 66.22 (d), 68.90 (t),
69.90 (d), 94.91 (d), 127.65 (3 × d), 128.24 (2 × d), 137.44 (s),
170.23 (s), 170.68 (s); MS (EI) m/z (rel intensity) 323 ([M +
H]+, 1), 263 (1), 231 (1), 215 (100), 181 (15), 156 (34), 143 (99),
129 (31), 91 (98). Anal. Calcd for C17H22O6: C, 63.34; H, 6.88.
Found: C, 63.33; H, 6.93.
Ben zyl 3,4-Did eoxy-r-D-er yth r o-h exop yr a n osid e (7).
To a solution of diacetate 6 (1.05 g, 3.26 mmol) in MeOH (45
mL) was added K2CO3 (901 mg, 6.52 mmol), and the solution
was stirred at room temperature for 3 h. The reaction mixture
was then poured into brine and extracted with CHCl3. The
organic extracts were dried over Na2SO4 and concentrated
under reduced pressure to give the title compound 7 (776 mg,
3.26 mmol, 100%): [R]D +116.1° (c ) 0.260); IR 3582, 2944,
1048 cm-1; 1H NMR 1.39-1.98 (6H, m), 3.51 (1H, dd, J ) 6.5,
11.5 Hz), 3.62 (1H, dd, J ) 3.3, 11.5 Hz), 3.64 (1H, m), 3.84
(1H, dddd, J ) 0, 3.2, 6.4, 9.7 Hz), 4.56 (1H, d, J ) 11.7 Hz),
4.80 (1H, d, J ) 11.7 Hz), 4.94 (1H, d, J ) 3.6 Hz), 7.31-7.39
(5H, m); 13C NMR 25.91 (t), 26.98 (t), 65.28 (t), 68.11 (d), 69.06
(d), 69.38 (t), 97.70 (d), 127.89 (d), 127.95 (2 × d), 128.46 (2 ×
d), 137.45 (s); MS (EI) m/z (rel intensity) 239 ([M + H]+, 7),
238 (M+, 1), 237 ([M - H]+, 3), 221 (54), 203 (6), 147 (2), 131
(25), 129 (47), 91 (100). Anal. Calcd for C13H18O4: C, 65.53;
H, 7.61. Found: C, 65.29; H, 7.62.
6-O-(ter t-Bu tyld ip h en ylsilyl)-3,4-d id eoxy-2-O-m eth yl-
D-er yth r o-h exop yr a n ose (10). To a solution of compound 9
(370 mg, 0.755 mmol) in dry CH2Cl2 (20 mL) was added, under
nitrogen, the complex boron trichloride-dimethyl sulfide (812
mg, 4.53 mmol), and the solution was stirred at room temper-
ature for 14 h. The reaction mixture was then poured into an
aqueous saturated solution of NaHCO3 and extracted with
CH2Cl2. The combined extracts were dried over Na2SO4 and
concentrated under reduced pressure. Chromatotron chroma-
tography (hexanes-EtOAc, 80:20) of the residue gave the title
compound 10 (225 mg, 0.562 mmol, 74%) as an anomeric
Ben zyl 6-O-(ter t-Bu tyld ip h en ylsilyl)-3,4-d id eoxy-r-D-
er yth r o-h exop yr a n osid e (8). To a solution of diol 7 (365 mg,
1.53 mmol) in dry DMF (22 mL) were added tert-butyldiphen-
ylsilyl chloride (0.92 mL, 3.53 mmol) and imidazole (480 mg,
7.06 mmol), and the solution was stirred at room temperature
for 5 min. The reaction mixture was then poured into 10%
HCl and extracted with CH2Cl2. The extracts were washed
with brine, dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified by column chromatography
(hexanes-EtOAc, 97:3 f 80:20) to give compound 8 (578 mg,
1.21 mmol, 79%) and benzyl 2,6-di-O-(tert-butyldiphenylsilyl)-
3,4-dideoxy-R-D-erythro-hexopyranoside (230 mg, 0.322 mmol,
1
mixture (R:â, 1:1): IR 3598, 3072, 2835, 1112 cm-1; H NMR
1.07 (18H, s), 1.28-1.55 (3H, m), 1.68-1.98 (4H, m), 2.15-
2.24 (1H, m), 2.89-3.01 (2H, m), 3.26-3.35 (2H, m), 3.41 (3H,
s), 3.47 (3H, s), 3.51-3.83 (3H, m), 4.04 (1H, dddd, J ) 2.0,
5.3, 5.3, 11.0 Hz), 4.53 (1H, d, J ) 7.4 Hz), 5.29 (1H, d, J )
3.3 Hz), 7.34-7.48 (12H, m), 7.65-7.71 (8H, m); 13C NMR
19.15 (s), 19.19 (s), 22.22 (t), 26.56 (t), 26.77 (6 × q), 26.92 (t),
27.29 (t), 56.14 (q), 57.59 (q), 66.32 (t), 66.55 (t), 68.57 (d), 75.99
(d), 77.18 (d), 79.74 (d), 90.47 (d), 98.34 (d), 127.54 (8 × d),
129.53 (4 × d), 133.51 (4 × s), 135.49 (4 × d), 135.55 (4 × d);
MS (EI) m/z (rel intensity) 383 ([M - OH]+, 8), 343 (5), 325
(8), 305 (92), 265 (13), 249 (16), 221 (91), 199 (100). Anal. Calcd
for C23H32O4Si: C, 68.96; H, 8.05. Found: C, 69.13; H, 8.18.
6-O-(ter t-Bu tyld ip h en ylsilyl)-1,3,4-tr id eoxy-2-O-m eth -
yl-1-(4′-p en ten yl)-â-D-er yth r o-h exop yr a n ose (11) a n d 6-O-
(ter t-Bu tyld ip h en ylsilyl)-1,3,4-tr id eoxy-2-O-m eth yl-1-(4′-
p en ten yl)-r-D-er yth r o-h exop yr a n ose (12). To a solution of
compound 10 (100 mg, 0.25 mmol) in dry THF (2 mL) were
added, under nitrogen, CCl4 (0.290 mL, 3 mmol) and Ph3P (328
mg, 1.25 mmol), and the solution was stirred at reflux
temperature for 3 h. The reaction mixture was cooled at room
temperature, filtered over Celite 545, and concentrated under
reduced pressure. The residue (105 mg) was dissolved in dry
Et2O (2.5 mL) and treated at 0 °C under nitrogen with a freshly
prepared solution of 4-pentenylmagnesium bromide in Et2O
(2.73 mL, 0.3 mmol) and the reaction kept at 0 °C for 1 h. The
reaction mixture was then poured into an aqueous solution of
1
21%): [R]D +46.3° (c ) 0.438); IR 3072, 2930, 1112 cm-1; H
NMR 1.03 (9H, s), 1.04 (9H, s), 1.09-1.37 (2H, m), 1.57-1.67
(1H, m), 1.95-2.14 (1H, m), 3.45 (1H, dd, J ) 5.0, 10.4 Hz),
3.58 (1H, dd, J ) 6.1, 10.4 Hz), 3.73 (1H, ddd, J ) 3.6, 3.6,
11.4 Hz), 3.83 (1H, dddd, J 1.9, 5.8, 5.8, 10.5 Hz), 4.47 (1H, d,
J ) 12.3 Hz), 4.57 (1H, d, J ) 3.3 Hz), 4.74 (1H, d, J ) 12.3
Hz), 7.28-7.44 (17H, m), 7.57-7.67 (8H, m); 13C NMR 19.19
(2 × q), 26.62 (t), 26.80 (3 × q), 26.88 (3 × q), 27.08 (t), 66.75
(t), 68.22 (t), 68.74 (d), 70.40 (d), 97.21 (d), 127.37 (d), 127.53
(4 × d), 127.57 (4 × d), 127.95 (2 × d), 128.21 (2 × d), 129.57
(4 × d), 133.58 (2 × s), 134.06 (2 × s), 135.57-135.75 (8 × d),
138.16 (s); MS (EI) m/z (rel intensity) 549 ([M - BnOH - tBu]+,
1), 489 (Bu, 1), 411 (2), 401 (1), 363 (11), 267 (20), 239 (18),
213 (24), 199 (82), 91 (100). Anal. Calcd for C45H54O4Si2: C,
75.58; H, 7.61. Found: C, 75.25; H, 7.95. Compound 8: [R]D
1
+47.9° (c ) 0.196); IR 3576, 3070, 2932, 1063 cm-1; H NMR

Chiral Dispiroacetals from Carbohydrates
J . Org. Chem., Vol. 63, No. 7, 1998 2257
ammonium chloride and extracted with Et2O. The organic
extracts were dried over Na2SO4 and concentrated under
reduced pressure. Chromatotron chromatography (hexanes-
EtOAc, 98:2) of the residue gave compounds 11 (18 mg, 0.04
mmol, 16%) and 12 (66 mg, 0.146 mmol, 58%). Compound
11: [R]D -33.7° (c ) 0.326); IR 3072, 1639 cm-1; 1H NMR 1.06
(9H, s), 1.27-1.52 (3H, m), 1.54-1.91 (4H, m), 2.08 (2H, ddd,
J ) 0, 6.6, 13.3 Hz), 2.28 (1H, m), 2.84 (1H, ddd, J ) 4.5, 9.6,
9.6 Hz), 3.11 (1H, ddd, J ) 2.5, 8.7, 8.7 Hz), 3.36 (3H, s), 3.43
(1H, m), 3.56 (1H, dd, J ) 5.1, 10.2 Hz), 3.73 (1H, dd, J ) 5.7,
10.2 Hz), 4.94 (1H, br dd, J ) 1.2, 10.1 Hz), 5.01 (1H, br dd, J
) 1.2, 17.1 Hz), 5.83 (1H, dddd, J ) 6.6, 6.6, 10.1, 17.0 Hz),
7.34-7.46 (6H, m), 7.68-7.73 (4H, m); 13C NMR 1.21 (s), 24.78
(t), 26.76 (3 × q), 27.37 (t), 28.32 (t), 31.80 (t), 33.91 (t), 56.42
(q), 66.83 (t), 77.63 (d), 79.29 (d), 80.40 (d), 114.16 (t), 127.53
(4 × d), 129.50 (2 × d), 133.69 (s), 133.74 (s), 135.60 (4 × d),
139.06 (d); MS (EI) m/z (rel intensity) 451 ([M - H]+, 2), 421
(5), 395 (97), 375 (48), 363 (100), 343 (32), 267 (40), 239 (21),
213 (25), 199 (57). Anal. Calcd for C28H40O3Si: C, 74.29; H,
8.91. Found: C, 74.03; H, 8.93. Compound 12: [R]D +16.0°
m), 7.65-7.71 (4H, m); 13C NMR 19.21 (s), 21.48 (t), 23.35 (t),
24.63 (t), 25.92 (t), 26.83 (3 × q), 32.67 (t), 56.39 (q), 62.83 (t),
66.34 (t), 69.54 (d), 73.64 (d), 77.01 (d), 127.62 (4 × d), 129.62
(2 × d), 133.59 (2 × s), 135.61 (4 × d); MS (EI) m/z (rel
intensity) 399 ([M - tBu]+, 17), 367 (48), 349 (9), 321 (23), 289
(66), 241 (22), 199 (51), 151 (100). Anal. Calcd for C27H40O4-
Si: C, 71.01; H, 8.83. Found: C, 71.16; H, 8.90.
Reaction of 6-O-(ter t-Bu tyldiph en ylsilyl)-1,3,4-tr ideoxy-
1-(4′-h yd r oxyb u t yl)-2-O-m et h yl-â-D-er yth r o-h exop yr a -
n ose (13) w ith DIB/I2. A solution of alcohol 13 (72 mg, 0.158
mmol) in cyclohexane (7 mL) containing DIB (72 mg, 0.221
mmol) and iodine (40 mg, 0.158 mmol) under nitrogen was
irradiated at 40 °C for 1 h with two 100 W tungsten-filament
lamps at 40 °C for 70 min. The reaction mixture was then
poured into aqueous saturated Na2S2O3, extracted with CH2-
Cl2, dried over Na2SO4, and concentrated. Chromatotron
chromatography of the reaction residue (hexanes-EtOAc, 94:
6) gave (1R)-6-O-(tert-butyldiphenylsilyl)-1,3,4-trideoxy-2-O-
methyl-D-erythro-hexopyranose-1-spiro-2′-tetrahydropyran (16)
(23.7 mg, 0.052 mmol, 33%) and (1S)-6-O-(tert-butyldiphenyl-
silyl)-1,3,4-trideoxy-2-O-methyl-D-erythro-hexopyranose-1-spiro-
2′-tetrahydropyran (15) (34.5 mg, 0.076 mmol, 48%). Com-
1
(c ) 0.300); IR 3073, 1639 cm-1; H NMR 1.06 (9H, s), 1.35-
1.89 (8H, m), 2.11 (2H, ddd, J ) 0, 6.7, 13.3 Hz), 3.34 (3H, s),
3.37 (1H, m), 3.51-3.71 (3H, m), 3.94 (1H, ddd, J ) 4.2, 4.2,
10.8 Hz), 4.96 (1H, br dd, J ) 1.7, 10.2 Hz), 5.02 (1H, br dd, J
) 1.8, 17.1 Hz), 5.82 (1H, dddd, J ) 6.8, 6.8, 10.2, 17.0 Hz),
7.30-7.48 (6H, m), 7.65-7.72 (4H, m); 13C NMR 19.18 (s),
23.44 (t), 24.07 (t), 24.54 (t), 26.13 (t), 26.81 (3 × q), 33.70 (t),
56.34 (q), 66.46 (t), 69.36 (d), 73.61 (d), 77.04 (d), 114.44 (t),
127.58 (4 × d), 129.56 (2 × d), 133.58 (2 × s), 135.58 (4 × d),
138.85 (d); MS (EI) m/z (rel intensity) 451 ([M - H]+, 1), 421
(9), 395 (90), 375 (57), 363 (100), 343 (49), 267 (33), 239 (16),
213 (21), 199 (43), 147 (93). Anal. Calcd for C28H40O3Si: C,
74.29; H, 8.91. Found: C, 74.17; H, 8.81
pound 16: [R]D -29.5° (c ) 0.220); IR 3072, 2950, 1113 cm-1
;
1H NMR 1.07 (9H, s), 1.25-1.81 (8H, m), 1.93-2.05 (2H, m),
3.03 (1H, dd, J ) 4.7, 10.8 Hz), 3.44 (3H, s), 3.54-3.83 (4H,
m), 4.10 (1H, ddd, J ) 2.6, 11.4, 11.4 Hz), 7.34-7.44 (6H, m),
7.66-7.73 (4H, m); 13C NMR 17.25 (t), 19.15 (s), 22.64 (t), 24.80
(t), 25.31 (t), 26.75 (3 × q), 26.75 (t), 57.95 (q), 61.42 (t), 66.80
(t), 72.67 (d), 81.81 (d), 99.16 (s), 127.60 (4 × d), 129.57 (2 ×
d), 133.57 (2 × s), 135.55 (4 × d); MS (EI) m/z (rel intensity)
454 (M+, 1), 423 (4), 397 (7), 365 (100), 345 (26), 267 (40), 239
(36), 199 (38), 183 (36). Anal. Calcd for C27H38O4Si: C, 71.33;
H, 8.43. Found: C, 71.35; H, 8.44. Compound 15: mp 100.2-
101.8 °C (from acetone-n-hexane); [R]D +5.3° (c ) 0.304); IR
6-O-(ter t-Bu t yld ip h en ylsilyl)-1,3,4-t r id eoxy-1-(4′-h y-
d r oxybu tyl)-2-O-m eth yl-â-D-er yth r o-h exop yr a n ose (13).
A solution of compound 11 (102 mg, 0.226 mmol) in CH2Cl2/
MeOH (15 mL, 1:1) was cooled at -78 °C, and ozone was
introduced into the solution until it became blue. Then
nitrogen was bubbled through the solution to expel excess
ozone, and the mixture was allowed to warm to 0 °C. NaBH4
(68 mg, 1.808 mmol) was added and the solution stirred for
12 h at room temperature. The reaction mixture was then
poured into an aqueous solution of 10% HCl, extracted with
CHCl3, dried over Na2SO4, and concentrated under reduced
pressure. Chromatotron chromatography of the residue (hex-
anes-EtOAc, 80:20) gave the title compound 13 (92 mg, 0.202
1
3072, 2933, 1113 cm-1; H NMR 1.07 (9H, s), 1.27-1.48 (3H,
m), 1.56-1.84 (4H, m), 1.89-2.14 (3H, m), 2.93 (1H, dd, J )
4.8, 11.0 Hz), 3.38 (3H, s), 3.60 (1H, dd, J ) 4.5, 10.0 Hz),
3.66-3.85 (3H, m), 3.70 (1H, dd, J ) 5.9, 10.1 Hz), 7.36-7.44
(6H, m), 7.70-7.78 (4H, m); 13C NMR 18.26 (t), 19.23 (s), 22.43
(t), 24.93 (t), 26.78 (3 × q), 27.03 (t), 30.64 (t), 57.19 (q), 60.57
(t), 66.87 (t), 69.43 (d), 81.57 (d), 96.47 (s), 127.61 (2 × d),
127.72 (2 × d), 129.57 (d), 129.58 (d), 133.76 (2 × s), 135.66 (2
× d), 135.68 (2 × d); MS (EI) m/z (rel intensity) 423 ([M -
MeO]+, 1), 397 (7), 365 (100), 345 (10), 267 (67), 239 (59), 199
(42), 183 (41). Anal. Calcd for C27H38O4Si: C, 71.33; H, 8.43.
Found: C, 71.61; H, 8.05.
mmol, 89%): [R]D -43.6° (c ) 0.204); IR 3618, 3072, 1112 cm-1
;
Isom er iza tion of (1R)-6-O-(ter t-Bu tyld ip h en ylsilyl)-
1,3,4-tr ideoxy-2-O-m eth yl-D-er yth r o-h exopyr an ose-1-spir o-
2′-tetr a h yd r op yr a n (16). To a solution of spiro compound
16 (25 mg, 0.055 mmol) in acetic acid (2 mL) was added a 0.3
M solution of HCl in acetic acid (0.25 mL). The mixture was
stirred at room temperature for 2 h, poured into an aqueous
solution of NaOH (10%), and extracted with CH2Cl2. The
combined extracts were dried over Na2SO4 and concentrated
under reduced pressure to give spiro compound 15 (25 mg,
0.055 mmol, 100%).
1H NMR 1.06 (9H, s), 1.26-1.87 (10H, m), 2.27 (1H, m), 2.84
(1H, ddd, J ) 4.3, 9.8, 9.8 Hz), 3.11 (1H, ddd, J ) 2.5, 8.8, 8.8
Hz), 3.36 (3H, s), 3.43 (1H, m), 3.55 (1H, dd, J ) 5.2, 10.3 Hz),
3.63 (2H, t, J ) 6.3 Hz), 3.72 (1H, dd, J ) 5.9, 10.3 Hz), 7.33-
7.47 (6H, m), 7.67-7.73 (4H, m); 13C NMR 19.18 (s), 21.56 (t),
26.72 (3 × q), 27.32 (t), 28.23 (t), 31.74 (t), 32.69 (t), 56.38 (q),
62.75 (t), 66.76 (t), 77.64 (d), 79.24 (d), 80.40 (d), 127.52 (4 ×
d), 129.51 (2 × d), 133.62 (s), 133.65 (s), 135.56 (4 × d); MS
(EI) m/z (rel intensity) 399 ([M - tBu]+, 17), 367 (24), 321 (6),
289 (21), 241 (22), 199 (100), 151 (55). Anal. Calcd for
Reaction of 6-O-(ter t-Bu tyldiph en ylsilyl)-1,3,4-tr ideoxy-
1-(4′-h yd r oxyb u t yl)-2-O-m et h yl-r-D-er yth r o-h exop yr a -
n ose (14) w ith DIB/I2. A solution of alcohol 14 (75 mg, 0.164
mmol) in cyclohexane (7.5 mL) containing DIB (85 mg, 0.262
mmol) and iodine (41 mg, 0.164 mmol) under nitrogen was
irradiated in a manner similar to that described above for 13.
Chromatotron chromatography (hexanes-EtOAc, 95:5) of the
residue gave (1R,3′S)-6-O-(tert-butyldiphenylsilyl)-1,3,4-trideoxy-
2-O-methyl-D-erythro-hexopyranose-1-spiro-2′-[(3′-iodo)tetrahy-
dropyran] (18) (2 mg, 0.003 mmol, 2%), compound 16 (16.5 mg,
0.036 mmol, 22%), (1R,3′R)-6-O-(tert-butyldiphenylsilyl)-1,3,4-
trideoxy-2-O-methyl-D-erythro-hexopyranose-1-spiro-2′-[(3′-
iodo)tetrahydropyran] (17) (11.6 mg, 0.02 mmol, 12%), and
compound 15 (22 mg, 0.048 mmol, 29%). Compound 18: [R]D
C
27H40O4Si: C, 71.01; H, 8.83. Found: C, 71.22; H, 8.89.
6-O-(ter t-Bu t yld ip h en ylsilyl)-1,3,4-t r id eoxy-1-(4′-h y-
d r oxybu tyl)-2-O-m eth yl-r-D-er yth r o-h exop yr a n ose (14).
A solution of compound 12 (240 mg, 0.531 mmol) in CH2Cl2/
MeOH (35 mL, 1:1) was cooled at -78 °C, and ozone was
introduced into the solution until it became blue. Then
nitrogen was bubbled through the solution to expel excess
ozone, and the mixture was allowed to warm to 0 °C. NaBH4
(81 mg, 2.12 mmol) was added and the solution stirred for 4 h
at room temperature. The reaction mixture was then poured
into an aqueous solution of 10% HCl, extracted with CHCl3,
dried over Na2SO4, and concentrated under reduced pressure.
Chromatotron chromatography of the residue (hexanes-
EtOAc, 90:10 f 75:25) gave the title compound 14 (230 mg,
1
+11.3° (c ) 0.142); IR 3068, 2931, 1104 cm-1; H NMR 1.05
0.50 mmol, 95%): [R]D +16.3° (c ) 0.166); IR 3626, 1112 cm-1
;
(9H, s), 1.32-1.49 (2H, m), 1.61-1.80 (2H, m), 1.97-2.19 (3H,
m), 2.61 (1H, m), 3.17 (1H, dd, J ) 4.9, 10.5 Hz), 3.36 (3H, s),
3.56 (1H, dd, J ) 4.4, 10.5 Hz), 3.66 (1H, dd, J ) 6.0, 10.5
Hz), 3.78-3.90 (3H, m), 4.09 (1H, t, J ) 4.3 Hz), 7.34-7.44
1H NMR 1.06 (9H, s), 1.26-1.69 (10H, m), 1.74-1.88 (2H, m),
3.34 (3H, s), 3.36 (1H, m), 3.52-3.73 (3H, m), 3.63 (2H, t, J )
6.4 Hz), 3.93 (1H, ddd, J ) 3.8, 3.8, 10.9 Hz), 7.33-7.47 (6H,

2258 J . Org. Chem., Vol. 63, No. 7, 1998
Dorta et al.
(6H, m), 7.67-7.73 (4H, m); 13C NMR 19.18 (s), 22.66 (t), 23.56
(t), 26.44 (t), 26.74 (3 × q), 28.83 (d), 31.93 (t), 56.21 (q), 60.76
(t), 66.59 (t), 70.78 (d), 81.49 (d), 95.11 (s), 127.64 (4 × d),
129.62 (2 × d), 133.52 (2 × s), 135.61 (4 × d); MS (EI) m/z (rel
s), 2.86 (1H, dd, J ) 4.8, 11.1 Hz), 3.35 (3H, s), 3.54-3.70 (2H,
m), 3.85 (1H, m), 3.99 (2H, d, J ) 4.7 Hz), 7.35 (2H, d, J ) 8.1
Hz), 7.81 (2H, d, J ) 8.2 Hz); 13C NMR 17.76 (t), 21.35 (q),
21.75 (t), 24.47 (t), 26.27 (t), 29.99 (t), 56.96 (q), 60.55 (t), 66.04
(d), 71.92 (t), 80.64 (d), 96.39 (s), 127.59 (2 × d), 129.54 (2 ×
d), 132.83 (s), 144.49 (s); MS (EI) m/z (rel intensity) 371 ([M +
H]+, 3), 370 (M+, 2), 369 ([M - H]+, 3), 339 (19), 198 (3), 167
(10), 155 (8), 101 (17), 58 (100).
t
intensity) 523 ([M - Bu]+, 2), 491 (18), 453 (6), 421 (3), 395
(92), 363 (33), 267 (34), 239 (12), 169 (100). Anal. Calcd for
C
27H37O4SiI: C, 55.86; H, 6.42. Found: C, 55.71; H, 6.65.
Compound 17: [R]D +38.1° (c ) 0.304); IR 3072, 2932, 1104
cm-1; 1H NMR 1.06 (9H, s), 1.27-1.50 (2H, m), 1.58-1.75 (2H,
m), 1.79-2.04 (2H, m), 2.31 (1H, m), 2.67 (1H, dddd, J ) 4.1,
12.9, 12.9, 12.9 Hz), 3.46 (3H, s), 3.63 (1H, dd, J ) 3.2, 9.9
Hz), 3.68-3.98 (5H, m), 4.71 (1H, dd, J ) 4.5, 12.9 Hz), 7.39-
7.48 (6H, m), 7.74-7.83 (4H, m); 13C NMR 19.09 (s), 22.54 (t),
26.04 (t), 26.69 (3 × q), 28.90 (t), 30.96 (d), 32.84 (t), 57.27 (q),
60.13 (t), 66.31 (t), 71.14 (d), 79.34 (d), 96.59 (s), 127.69 (2 ×
d), 127.77 (2 × d), 129.51 (d), 129.59 (d), 133.36 (s), 133.55 (s),
135.68 (4 × d); MS (EI) m/z (rel intensity) 523 ([M - tBu]+, 1),
491 (5), 453 (5), 421 (4), 395 (83), 363 (20), 267 (33), 239 (29),
71 (100). Anal. Calcd for C27H37O4SiI: C, 55.86; H, 6.42.
Found: C, 55.72; H, 6.44.
Red u ction of (1R,3′R)-6-O-(ter t-Bu tyld ip h en ylsilyl)-
1,3,4-tr ideoxy-2-O-m eth yl-D-er yth r o-h exopyr an ose-1-spir o-
2′-[(3′-iod o)tetr a h yd r op yr a n ] (17). To a solution of iodide
17 (51 mg, 0.088 mmol) in dry benzene (8 mL) were added
under nitrogen tributyltin hydride (0.118 mL, 0.440 mmol) and
2,2′-azobis(isobutironitrile) (AIBN) (2 mg, 0.013 mmol). The
mixture was stirred at reflux temperature for 35 min, poured
into water, and extracted with CH2Cl2. The combined extracts
were dried over Na2SO4 and concentrated under reduced
pressure. Chromatotron chromatography of the residue (hex-
anes-EtOAc, 94:6) gave the spiroacetal 15 (38.8 mg, 0.085
mmol, 97%).
R ed u ct ion of (1R,3′S)-6-O-(ter t-Bu t yld ip h en ylsilyl)-
1,3,4-tr ideoxy-2-O-m eth yl-D-er yth r o-h exopyr an ose-1-spir o-
2′-[(3′-iod o)tetr a h yd r op yr a n ] (18). To a solution of iodide
18 (6.5 mg, 0.011 mmol) in dry benzene (1 mL) were added
under nitrogen tributyltin hydride (15.1 µL, 0.056 mmol) and
AIBN (1 mg, 0.006 mmol). The mixture was stirred at reflux
temperature for 35 min, poured into water, and extracted with
CH2Cl2. The combined extracts were dried over Na2SO4 and
concentrated under reduced pressure. Chromatotron chroma-
tography of the residue (hexanes-EtOAc, 94:6) gave the
spiroacetal 15 (4.1 mg, 0.009 mmol, 80%).
(1S)-6-Allyl-1,3,4,6-t et r a d eoxy-2-O-m et h yl-D-er yth r o-
h exop yr a n ose-1-sp ir o-2′-tetr a h yd r op yr a n (21). To a solu-
tion of p-toluenesulfonate 20 (83 mg, 0.224 mmol) in dry Et2O
(6 mL) was added, under nitrogen at 0 °C, allylmagnesium
bromide in Et2O (1.14 mL, 1.12 mmol). The mixture was
stirred at room temperature for 2 h, poured into an aqueous
solution of ammonium chloride, and extracted with CH2Cl2.
The combined extracts were dried over Na2SO4 and concen-
trated under reduced pressure. Chromatotron chromatogra-
phy (hexanes-EtOAc, 95:5) of the residue gave the title
compound 21 (46 mg, 0.192 mmol, 85%): 1H NMR 1.26-2.37
(14H, m), 2.91 (1H, dd, J ) 4.8, 11.1 Hz), 3.37 (3H, s), 3.54-
3.71 (3H, m), 4.97 (1H, dddd, J ) 1.7, 1.7, 1.7, 10.5 Hz), 5.04
(1H, dddd, J ) 1.7, 1.7, 1.7, 17.1 Hz), 5.87 (1H, dddd, J ) 6.6,
6.6, 10.3, 16.9 Hz); 13C NMR 18.26 (t), 22.57 (t), 24.93 (t), 30.29
(t), 30.70 (t), 30.97 (t), 34.97 (t), 57.06 (q), 60.60 (t), 67.77 (d),
81.54 (d), 96.28 (s), 114.34 (t), 138.62 (d); MS (EI) m/z (rel
intensity) 239 ([M - H]+, 3), 209 (1), 158 (34), 153 (2), 101
(22), 58 (100). Anal. Calcd for C14H24O3: C, 69.96; H, 10.06.
Found: C, 69.84; H, 9.93.
(1S)-1,3,4,6-Tetr a d eoxy-6-(2′′-h yd r oxyeth yl)-2-O-m eth -
yl-D-er yth r o-h exop yr a n ose-1-sp ir o-2′-t et r a h yd r op yr a n
(22). A solution of compound 21 (40 mg, 0.167 mmol) in CH2-
Cl2/MeOH (11 mL, 1:1) was cooled at -78 °C, and ozone was
introduced into the solution until it became blue. Then
nitrogen was bubbled through the solution to expel excess
ozone, and the mixture was allowed to warm to 0 °C. NaBH4
(19 mg, 0.50 mmol) was added and the solution stirred for 3 h
at room temperature. The reaction mixture was then poured
into an aqueous solution of 10% HCl, extracted with CHCl3,
dried over Na2SO4, and concentrated under reduced pressure.
Chromatotron chromatography of the residue (hexanes-
EtOAc, 70:30 f 60:40) gave the title compound 22 (39.8 mg,
0.163 mmol, 98%): [R]D +39.2° (c ) 0.51); IR 3636, 3457 cm-1
;
1H NMR 1.23-2.07 (14H, m), 2.18 (1H, br s), 2.88 (1H, dd, J
) 4.8, 11.1 Hz), 3.34 (3H, s), 3.53-3.71 (3H, m), 3.64 (2H, t, J
) 6.2 Hz); 1H NMR (C6D6) 1.20-1.35 (2H, m), 1.47-1.71 (7H,
m), 1.74-1.79 (1H, m), 1.83-2.03 (3H, m), 2.16 (1H, ddd, J )
4.1, 13.4, 13.4 Hz), 2.85 (1H, dd, J ) 4.6, 11.6 Hz), 3.17 (1H,
br s), 3.19 (3H, s), 3.58-3.65 (1H, m), 3.66-3.72 (4H, m); 13C
NMR 18.18 (t), 22.51 (t), 24.81 (t), 29.17 (t), 30.51 (t), 30.82
(t), 32.02 (t), 57.07 (q), 60.65 (t), 62.84 (t), 68.38 (d), 81.41 (d),
96.49 (s); 13C NMR (100.6, C6D6) 18.73 (t), 22.93 (t), 25.31 (t),
29.61 (t), 30.99 (t), 31.31 (t), 32.46 (t), 56.61 (q), 60.67 (t), 62.55
(t), 68.61 (d), 81.90 (d), 96.75 (s); MS (EI) m/z (rel intensity)
245 ([M + H]+, 4), 244 (M+, 1), 243 ([M - H]+, 4), 227 (10),
211 (19), 195 (31), 184 (100), 158 (100). Anal. Calcd for
(1S)-1,3,4-Tr ideoxy-2-O-m eth yl-D-er yth r o-h exopyr an ose-
1-sp ir o-2′-tetr a h yd r op yr a n (19). To a solution of spiro
compound 15 (63 mg, 0.139 mmol) in dry THF (4 mL) was
added under nitrogen tetrabutylammonium fluoride (91 mg,
0.347 mmol). The mixture was stirred at room temperature
for 2.5 h, poured into a saturated solution of NaHCO3, and
extracted with CHCl3. The organic layer was washed with
brine, dried with Na2SO4, and concentrated under reduced
pressure. Chromatotron chromatography (hexanes-EtOAc,
70:30) of the residue gave the title compound 19 (26.4 mg,
0.122 mmol, 88%): mp 88.0-89.2 °C (from Et2O); [R]D +43.3°
(c ) 0.164); IR 3600, 2944, 1066 cm-1 1H NMR 1.37-2.12
;
(11H, m), 2.92 (1H, dd, J ) 4.7, 11.2 Hz), 3.37 (3H, s), 3.50
(1H, dd, J ) 7.0, 11.3 Hz), 3.64 (1H, dd, J ) 3.3, 11.3 Hz),
3.69-3.82 (3H, m); 13C NMR 18.75 (t), 21.95 (t), 24.63 (t), 26.16
(t), 30.26 (t), 57.08 (q), 60.59 (t), 65.51 (t), 68.93 (d), 81.27 (d),
96.37 (s); MS (EI) m/z (rel intensity) 217 ([M + H]+, 23), 216
(M+, 3), 215 ([M - H]+, 7), 199 (2), 185 (34), 167 (3), 153 (17),
117 (26), 101 (100). Anal. Calcd for C11H20O4: C, 61.09; H,
9.32. Found: C, 61.39; H, 9.11.
C
13H24O4: C, 63.89; H, 9.91. Found: C, 63.83; H, 9.61.
Reaction of (1S)-1,3,4,6-Tetr adeoxy-6-(2′′-h ydr oxyeth yl)-
2-O-m et h yl-D-er yth r o-h exop yr a n ose-1-sp ir o-2′-t et r a h y-
d r op yr a n (22) w ith DIB/I2. A solution of alcohol 22 (20 mg,
0.082 mmol) in dry cyclohexane (5 mL) containing DIB (32 mg,
0.099 mmol) and iodine (21 mg, 0.082 mmol) under nitrogen
was irradiated at room temperature for 4 h in a manner
similar to that described above for 13. Column chromatogra-
phy of the reaction residue (hexanes-Et2O, 85:15 f 70:30)
gave (5S,7S,13R)-13-methoxy-1,6,8-trioxadispiro[4.1.5.3]pen-
tadecane (24) (4.6 mg, 0.019 mmol, 23%) and (5R,7S,13R)-13-
methoxy-1,6,8-trioxadispiro[4.1.5.3]pentadecane (23) (6.6 mg,
0.027 mmol, 33%). Compound 23: 1H NMR (C6D6) 1.27 (1H,
d, J ) 11.8 Hz), 1.42-1.49 (1H, m), 1.50-1.62 (3H, m), 1.75
(1H, br d, J ) 12.7 Hz), 1.82-1.89 (1H, m), 1.91-2.00 (4H,
m), 2.04-2.12 (2H, m), 2.31 (1H, ddd, J ) 3.1, 7.9, 12.3 Hz),
3.25 (3H, s), 3.26 (1H, dd, J ) 5.4, 8.8 Hz), 3.63-3.69 (1H, m),
3.73 (1H, ddd, J ) 7.3, 7.3, 7.3 Hz), 3.86 (1H, ddd, J ) 2.4,
12.5, 12.5 Hz), 4.02 (1H, ddd, J ) 4.8, 8.3, 8.3 Hz); 13C NMR
(C6D6) 19.1 (t), 21.4 (t), 24.8 (t), 25.7 (t), 31.9 (t), 32.8 (t), 37.4
(1S)-1,3,4-Tr ideoxy-2-O-m eth yl-6-O-tosyl-D-er yth r o-h ex-
op yr a n ose-1-sp ir o-2′-tetr a h yd r op yr a n (20). To a solution
of alcohol 19 (69 mg, 0.319 mmol) in dry pyridine (7 mL) was
added under nitrogen TsCl (244 mg, 1.276 mmol). The
reaction mixture was stirred at room temperature for 15 h,
poured into an aqueous solution of HCl (10%), and extracted
with CH2Cl2. The combined extracts were washed with brine,
dried over Na2SO4, and concentrated under reduced pressure.
Chromatotron chromatography of the residue (hexanes-
EtOAc, 85:15) gave the title compound 20 (118 mg, 0.319
mmol, 100%): [R]D +18.5° (c ) 0.362); IR 1363, 1176, 1099
cm-1; 1H NMR 1.26-1.82 (8H, m), 1.88-2.04 (2H, m), 2.45 (3H,

Chiral Dispiroacetals from Carbohydrates
J . Org. Chem., Vol. 63, No. 7, 1998 2259
(t), 57.2 (q), 60.8 (t), 67.4 (t), 80.4 (d), 98.0 (s), 107.0 (s). Anal.
Calcd for C13H22O4: C, 64.44; H, 9.15. Found: C, 64.32; H,
9.04. Compound 24: 1H NMR (C6D6) 1.36 (1H, br d, J ) 14.3
Hz), 1.52-1.75 (7H, m), 1.93 (1H, ddd, J ) 2.7, 2.7, 13.2 Hz),
1.97-2.07 (3H, m), 2.30 (1H, ddd, J ) 4.4, 13.3, 13.3 Hz), 2.63
(1H, dddd, J ) 3.3, 11.7, 13.8, 13.8 Hz), 2.97 (1H, dd, J ) 3.8,
11.7 Hz), 3.28 (3H, s), 3.80-3.89 (2H, m), 4.01-4.08 (2H, m);
13C NMR (C6D6) 19.3 (t), 19.8 (t), 24.7 (t), 25.8 (t), 32.3 (t), 34.9
(t), 40.0 (t), 56.03 (q), 61.5 (t), 69.2 (t), 82.5 (d), 97.6 (s), 105.9
(s); MS (EI) m/z (rel intensity) 241 ([M - H]+, 1), 225 ([M -
OH]+, 1), 211 (1), 183 (1), 169 (2), 85 (20), 57 (100). Anal. Calcd
for C13H22O4: C, 64.44; H, 9.15. Found: C, 64.23; H, 9.21.
1-[3′-(ter t-Bu t yld ip h en ylsilyl)p r op yl]-1,2,3-t r id eoxy-
4,6-O-isop r op ylid en e-r-D-er yth r o-h exop yr a n ose (26). A
stirred solution of olefin 25 (1.95 g, 4.2 mmol) in EtOAc (20
mL) was treated with 20% Pd(OH)2/C (195 mg, 10 wt %). A
hydrogen atmosphere was introduced by using a hydrogen-
filled balloon (repeated evacuation with aspirator). After
consummation of starting material (monitored by TLC), the
hydrogen was replaced with nitrogen. The reaction mixture
(1.8 g, 88%) and the ditosylate (214 mg, 8%): [R]D +23.7° (c )
1
1.29); IR (CCl4) 3071, 2931, 1956-1823, 1376, 1180 cm-1; H
NMR (C6D6) 1.10-1.62 (6H, m), 1.22 (9H, s), 1.66-1.71 (2H,
m), 1.88 (3H, s), 1.93 (3H, s), 3.22 (1H, m), 3.62 (2H, t, J ) 6.0
Hz), 3.75 (1H, ddd, J ) 5.4, 5.4, 5.4 Hz), 3.92 (1H, dd, J ) 5.6,
10.5 Hz), 4.05 (1H, dd, J ) 4.8, 10.5 Hz), 4.56 (1H, ddd, J )
5.6, 5.6, 5.6 Hz), 6.75 (2H, d, J ) 8.1 Hz), 6.83 (2H, d, J ) 8.1
Hz), 7.27-7.33 (6H, m), 7.76-7.88 (8H, m); 13C NMR 19.14
(s), 21.62 (2 × d), 25.17 (t), 25.95 (t), 26.83 (3 × q), 28.30 (t),
28.41 (t), 63.34 (t), 67.75 (t), 70.56 (d), 71.50 (2 × d), 74.80 (d),
127.59 (4 × d), 127.67 (2 × d), 127.90 (2 × d), 129.55 (2 × d),
129.75 (2 × d), 129.97 (2 × d), 132.68 (s), 133.55 (s), 133.83 (2
× s), 135.47 (4 × d), 144.86 (s), 145.07 (s). Anal. Calcd for
C
39H48O8S2Si: C, 63.56; H, 6.57; S, 8.69. Found: C, 63.31; H,
6.55; S, 9.02. Compound 28: [R]D +8.1° (c ) 0.54); IR (CCl4)
3564, 3071, 2944, 1956-1823, 1371, 1178 cm-1; 1H NMR (C6D6)
1.24 (9H, s), 1.56-1.68 (9H, m), 1.86 (3H, s), 3.32-3.58 (3H,
m), 3.66 (2H, t, J ) 6.2 Hz), 4.14 (1H, dd, J ) 2.5, 10.4 Hz),
4.32 (1H, dd, J ) 4.9, 10.4 Hz), 6.72 (2H, d, J ) 8.1 Hz), 7.28-
7.34 (6H, m), 7.79-7.86 (6H, m); 13C NMR 19.16 (s), 21.59 (q),
26.85 (3 × q), 26.98 (t), 27.18 (t), 28.70 (t), 63.48 (t), 65.58 (d),
69.35 (t), 71.90 (d), 72.97 (d), 127.59 (4 × d), 127.91 (2 × d),
129.54 (2 × d), 129.79 (2 × d), 132.88 (s), 133.92 (2 × s), 135.50
(4 × d), 144.84 (s); MS (EI, 30 eV) m/z (rel intensity) 525 ([M
was filtered through
a Celite pad, and the filtrate was
concentrated, followed by chromatography (hexanes-EtOAc,
95:5) to afford the reduced product 26 (1.569 g, 80%) along
with the isomeric enol-ether 1-[3′-(tert-butyldiphenylsilyl)-
propyl]-1,2,3-trideoxy-4,6-O-isopropylidene-D-erythro-hex-1-
enopyranose (279 mg, 14%): [R]D +32.6° (c ) 2.1); IR (CCl4)
3072, 2931, 1957-1823, 1671, 1428, 1103 cm-1; 1H NMR 1.06
(9H, s), 1.44 (3H, s), 1.54 (3H, s), 1.65-1.78 (2H, m), 2.05-
2.20 (4H, m), 3.54 (1H, ddd, J ) 5.4, 9.1, 10.7 Hz), 3.66 (2H,
t, J ) 6.3 Hz), 3.77 (1H, dd, J ) 10.8, 10.8 Hz), 3.87 (1H, ddd,
J ) 6.2, 9.2, 9.2 Hz), 3.96 (1H, dd, J ) 5.5, 10.8 Hz), 4.44 (1H,
dd, J ) 2.0, 5.0 Hz), 7.35-7.44 (6H, m), 7.65-7.70 (4H, m);
13C NMR 19.09 (q), 19.19 (s) 26.84 (3 × q), 27.26 (t), 29.21 (q),
29.77 (t), 29.81 (t), 62.40 (t), 63.07 (t), 67.46 (d), 70.85 (d), 93.47
(d), 99.26 (s), 127.56 (4 × d), 129.51 (2 × d), 133.95 (2 × s),
135.53 (4 × d), 153.50 (s); MS (EI) m/z (rel intensity) 451 ([M
- CH3]+, 6), 409 (100), 351 (100), 295 (64), 273 (47), 255 (24),
211 (35), 199 (100). Anal. Calcd for C28H38O4Si: C, 72.06; H,
8.21. Found: C, 71.96; H, 7.88. Compound 26: [R]D +18.2°
(c ) 1.46); IR (CCl4) 3072, 2946, 1957-1823, 1428, 1200, 1094
t
- Bu]+, 3), 353 (100), 293 (71), 275 (50), 199 (77), 155 (8).
Anal. Calcd for C32H42O6SSi: C, 65.95; H, 7.27; S, 5.49.
Found: C, 65.84; H, 7.37; S, 5.52.
6-Allyl-1-[3′-(ter t-bu tyld ip h en ylsilyl)p r op yl]-1,2,3,6-tet-
r a d eoxy-r-D-er yth r o-h exop yr a n ose (29). To a solution of
tosylate 28 (1.8 g, 3.09 mmol) in dry Et2O (50 mL) was added,
under nitrogen at 0 °C, allylmagnesium bromide (7 mL, 7
mmol, 1 M in Et2O). The reaction mixture was stirred at 0
°C for 3 h, the cooling bath removed, and stirring continued
at room temperature for 1 h. The reaction mixture was poured
into aqueous saturated ammonium chloride and extracted with
Et2O, followed by washing with aqueous saturated NaHCO3
and brine, dried over Na2SO4, and concentrated under reduced
pressure. Column chromatograpy (hexanes-EtOAc, 90:10) of
the residue gave the title compound 29 (1.12 g, 80%): [R]D
+22.3° (c ) 0.68); IR (CCl4) 3626, 3593, 3072, 2932, 1956-
1
1
cm-1; H NMR 1.09 (9H, s) 1.43-1.72 (7H, m), 1.50 (3H, s),
1823, 1640, 1112 cm-1
;
NMR (C6D6) 1.23 (9H, s), 1.28-1.84
1.56 (3H, s), 1.88-2.05 (1H, m), 3.37 (1H, ddd, J ) 5.7, 9.1,
9.1 Hz), 3.55-3.72 (5H, m, 4-H), 3.85 (1H, m), 7.37-7.45 (6H,
m), 7.66-7.71 (4H, m); 13C NMR 19.16 (q), 19.16 (s), 24.76 (t),
26.09 (t), 26.85 (3 × d), 28.05 (t), 28.88 (t), 29.35 (q), 63.30 (t),
63.46 (t), 66.77 (d), 71.28 (d), 72.80 (d), 99.27 (s), 127.57 (4 ×
d), 129.52 (2 × d), 133.89 (2 × s), 135.49 (4 × d); MS (EI) m/z
(rel intensity) 453 ([M - CH3]+, 7), 411 (30), 353 (14), 275 (21),
255 (4), 213 (7), 199 (100). Anal. Calcd for C28H40O4Si: C,
71.75; H, 8.60. Found: C, 71.63; H, 8.67.
1-[3′-(ter t-Bu tyld ip h en ylsilyl)p r op yl]-1,2,3-tr id eoxy-r-
D-er yth r o-h exop yr a n ose (27). A mixture of the acetonide
26 (2.04 g, 4.36 mmol), Amberlyst-15 (H+) ion-exchange resin
(600 mg), and MeOH (40 mL) was stirred at room temperature
for 1 h. The Amberlyst resin was removed by filtration, the
filtrate was concentrated, and the residue was chromato-
graphed (hexanes-Et2O, 10:90) to afford the diol 27 (1.64 g,
88%): [R]D +20.2° (c ) 1.03); 1H NMR 1.07 (9H, s), 1.47-1.91
(8H, m), 2.22 (2H, bs), 3.44 (1H, m), 3.56 (1H, m), 3.68-3.79
(5H, m), 7.36-7.44 (6H, m), 7.65-7.70 (4H, m); 13C NMR 19.15
(s), 26.84 (3 × d), 26.99 (t), 27.22 (t), 27.38 (t), 28.83 (t), 62.65
(t), 63.56 (t), 66.94 (d), 71.64 (d), 74.33 (d), 127.57 (4 × d),
129.53 (2 × d), 133.89 (2 × s), 135.50 (4 × d); MS (EI) m/z (rel
intensity) 371 ([M - tBu]+, 2), 323 (1), 293 (93), 275 (36), 255
(7), 245 (18), 199 (100). Anal. Calcd for C25H36O4Si: C, 70.05;
H, 8.47. Found: C, 70.33; H, 8.65.
(11H, m), 2.08-2.28 (2H, m), 3.22 (1H, ddd, J ) 5.2, 5.2, 5.2
Hz), 3.40-3.49 (2H, m), 3.75 (2H, t, J ) 6.0 Hz), 5.05 (1H, dd,
J ) 1.1, 10.2 Hz), 5.12 (1H, dd, J ) 1.4, 17.1 Hz), 5.85 (1H,
dddd, J ) 6.6, 6.6, 10.3, 17.0 Hz), 7.28-7.32 (6H, m), 7.81-
7.88 (4H, m); 13C NMR 19.19 (s), 26.58 (t), 26.77 (t), 26.86 (3
× d), 28.73 (t), 29.47 (t), 29.76 (t), 30.18 (t), 63.68 (t), 68.63
(d), 69.60 (d), 76.12 (d), 114.85 (t), 127.57 (4 × d), 129.50 (2 ×
d), 133.98 (2 × s), 135.53 (4 × d), 138.18 (d); MS (EI) m/z (rel
t
intensity) 435 ([M - OH]+, 2), 395 ([M - Bu]+, 40), 377 (5),
317 (6), 299 (5), 275 (17), 199 (100). Anal. Calcd for C28H40O3-
Si: C, 74.29; H, 8.91. Found: C, 74.20; H, 8.79.
6-Allyl-1-[3′-(ter t-bu tyld ip h en ylsilyl)p r op yl]-1,2,3,6-tet-
r a d eoxy-4-O-m eth yl-r-D-er yth r o-h exop yr a n ose (30). To
a vigorously stirred suspension of the alcohol 29 (890 mg, 1.98
mmol) and pulverized sodium hydroxide (712 mg, 17.82 mmol)
in dry acetone (7 mL) was added dropwise dimethyl sulfate
(0.943 mL, 9.9 mmol) at 30 °C, after which the temperature
was raised to 50 °C and maintained for 4 h. The cooled
mixture was poured into ice-water and extracted with CHCl3.
Drying over Na2SO4 and concentration followed by chroma-
tography (hexanes-EtOAc, 99:1) furnished the methyl ether
30 (669 mg, 73%) and starting alcohol 29 (232 mg, 25%) which
was recycled. Compound 30: [R]D +26.0° (c ) 0.48); IR (CCl4)
3072, 2941, 2830, 1956-1823, 1640, 1111 cm-1; 1H NMR (C6D6)
1.23 (9H, s), 1.37-1.87 (10H, m), 2.16-2.36 (2H, m), 2.78 (1H,
ddd, J ) 4.1, 5.9, 5.9 Hz), 3.51 (3H, s), 3.55 (1H, m), 3.71 (1H,
m), 3.74 (2H, t, J ) 6.0 Hz), 5.05 (1H, dd, J ) 1.0, 10.2 Hz),
5.15 (1H, dd, J ) 1.7, 17.0 Hz), 5.92 (1H, dddd, J ) 6.6, 6.6,
10.3, 16.9 Hz), 7.26-7.32 (6H, m), 7.80-7.87 (4H, m); 13C NMR
19.19 (s), 23.27 (t), 26.85 (3 × d), 27.85 (t), 28.84 (t), 29.80 (t),
29.97 (2 × t), 56.24 (q), 63.76 (t), 69.95 (d), 73.14 (d), 77.88
(d), 114.67 (t), 127.55 (4 × d), 129.47 (2 × d), 134.02 (2 × s),
135.53 (4 × d), 138.42 (d); MS (EI) m/z (rel intensity) 467 ([M
1-[3′-(ter t-Bu tyld ip h en ylsilyl)p r op yl]-1,2,3-tr id eoxy-6-
O-tosyl-r-D-er yth r o-h exop yr a n ose (28). To a stirred solu-
tion of the diol 27 (1.52 g, 3.55 mmol) in dry pyridine (6.5 mL)
at 0 °C was added TsCl (1 g, 5.25 mmol). After 4 h at 0 °C the
excess TsCl was quenched with MeOH (1.2 mL), and the
heterogeneous mixture was stirred for 20 min. The reaction
mixture was diluted with Et2O and sequentially washed with
H2O and brine. Drying (Na2SO4), concentration, and chroma-
tography (hexanes-EtOAc, 90:10) gave the monotosylate 28
t
+ H]+, 2], 409 ([M - Bu]+, 55), 377 (100), 331 (9), 295 (17),

2260 J . Org. Chem., Vol. 63, No. 7, 1998
Dorta et al.
269 (24), 213 (56), 199 (100). Anal. Calcd for C29H42O3Si: C,
74.63; H, 9.07. Found: C, 74.79; H, 8.79.
34 (21.5 mg, 43%): [R]D +47.1° (c ) 0.78); IR (CCl4) 3072, 2932,
2820, 1956-1823, 1112 cm-1; 1H NMR (C6D6) 1.08-1.12 (1H,
m), 1.17 (9H, s), 1.20-1.95 (12H, m), 2.25 (1H, brd, J ) 12.0
Hz), 2.92 (1H, t, J ) 2.5 Hz), 3.07 (3H, s), 3.50 (1H, m), 3.58-
3.62 (2H, m), 3.71-3.77 (2H, m), 7.21-7.23 (6H, m), 7.78-
7.81 (4H, m); 13C NMR (C6D6) 18.62 (t), 19.21 (s), 21.82 (t),
25.54 (t), 25.67 (t), 26.81 (3 × q), 29.23 (t), 32.19 (t), 32.64 (t),
56.56 (q), 60.04 (t), 64.35 (t), 68.80 (d), 78.61 (d), 96.36 (s),
127.74 (4 × d), 129.58 (2 × d), 134.25 (s), 134.28 (s), 135.99 (4
× d); MS (EI) m/z (rel intensity) 483 ([M + H]+, 1), 451 ([M -
MeO]+, 1), 393 (31), 387 (13), 325 (8), 267 (22), 177 (56), 111
(19), 58 (100). Anal. Calcd for C29H42O4Si: C, 72.16; H, 8.77.
Found: C, 72.13; H, 8.40.
1-[3′-(ter t-Bu tyldiph en ylsilyl)pr opyl]-1,2,3,6-tetr adeoxy-
6-(3′′-h yd r oxyp r op yl)-4-O-m eth yl-r-D-er yth r o-h exop yr a -
n ose (31). To a solution of olefin 30 (315 mg, 0.676 mmol) in
dry THF (1.5 mL) at 0 °C and under nitrogen was added
dropwise a solution of BH3‚THF complex (0.6 mL, 0.6 mmol, 1
M in THF). After 1 h of stirring, the excess borane was
quenched carefully by adding a drop of water. Dropwise
addition of a mixture of 3 N NaOH (0.5 mL) and 30% hydrogen
peroxide (0.25 mL), removal of the cooling bath, and continued
stirring for 20 min resulted in a white heterogeneous mixture.
Dilution with Et2O, followed by washing with H2O and brine,
drying over Na2SO4, concentration, and concentrated. Chro-
matotron chromatography (hexanes-EtOAc, 60:40), gave the
alcohol 31 (238 mg, 73%): [R]D +25.8° (c ) 0.84); IR (CCl4)
3626, 3072, 2940, 2820, 1956-1823, 1111 cm-1; 1H NMR (C6D6)
1.24 (9H, s), 1.38-1.85 (15H, m), 2.81 (1H, ddd, J ) 4.3, 4.3,
4.3 Hz), 3.17 (3H, s), 3.55 (2H, t, J ) 5.7 Hz), 3.56 (1H, m),
3.73 (1H, m), 3.75 (2H, t, J ) 6.0 Hz), 7.29-7.33 (6H, m), 7.82-
7.87 (4H, m); 13C NMR 19.15 (s), 21.89 (t), 23.16 (t), 26.82 (t),
26.82 (3 × q), 28.77 (t), 29.58 (t), 30.32 (t), 32.53 (t), 56.17 (q),
62.67 (t), 63.72 (t), 70.05 (d), 73.59 (d), 77.87 (d), 127.53 (4 ×
d), 129.45 (2 × d), 133.96 (2 × s), 135.48 (4 × d); MS (EI) m/z
(5S)-1-(3′-Hyd r oxyp r op yl)-1,2,3-tr id eoxy-4-O-m eth yl-r-
D-glycer o-pen topyr an ose-5-spir o-2′′-tetr ah ydr opyr an (35).
To a deoxygenated solution of compound 34 (30 mg, 0.062
mmol) in dry THF (1 mL) was added tetrabutylammonium
fluoride (50 mg, 0.165 mmol), and the mixture was stirred at
room temperature for 2 h. The solvent was removed under
reduced pressure, and the residue was dissolved in CH2Cl2,
washed with aqueous saturated NaHCO3 and brine, dried over
Na2SO4, and concentrated. Chromatotron chromatography
(hexanes-EtOAc, 70:30) gave the alcohol 35 (13 mg, 86%): [R]D
+72.1° (c ) 0.49); IR (CCl4) 3646, 3460, 2941, 2822, 1116 cm-1
;
t
(rel intensity) 427 ([M - Bu]+, 7), 395 (12), 317 (11), 269 (7),
1H NMR (C6D6) 1.33-2.02 (13H, m), 2.35 (1H, dddd, J ) 2.7,
2.7, 2.7, 13.2 Hz), 2.97 (1H, t, J ) 2.7 Hz), 3.12 (3H, s), 3.53-
3.71 (6H, m); 13C NMR (C6D6) 18.78 (t), 21.96 (t), 25.56 (t),
25.84 (t), 29.57 (t), 32.36 (t), 33.00 (t), 56.82 (q), 60.34 (t), 62.93
(t), 69.32 (d), 78.79 (d), 96.75 (s); MS (EI) m/z (rel intensity)
245 ([M + H]+, 4), 227 ([M - OH]+, 2), 213 (2), 195 (10), 184
(18), 158 (31), 128 (18), 101 (100). Anal. Calcd for C13H24O4:
C, 63.91; H, 9.90. Found: C, 64.06; H, 9.83.
229 (3), 199 (57), 161 (39), 58 (100). Anal. Calcd for C29 H44O4-
Si: C, 71.86; H, 9.16. Found: C, 72.01; H, 9.19.
1-(3′-H y d r o x y p r o p y l)-1,2,3,6-t e t r a d e o x y -6-(3′′-h y -
d r oxyp r op yl)-4-O-m eth yl-r-D-er yth r o-h exop yr a n ose (32).
To a deoxygenated solution of compound 31 (27 mg, 0.056
mmol) in dry THF (1.5 mL) was added tetrabutylammonium
fluoride (80 mg, 0.254 mmol), and the mixture was stirred at
room temperature for 2 h. The solvent was removed under
reduced pressure, and the residue was dissolved in CH2Cl2,
washed with aqueous saturated NaHCO3 and brine, dried over
Na2SO4, and concentrated. Chromatotron chromatography
(EtOAc f EtOAc-MeOH, 95:5) gave the alcohol 32 (13 mg,
95%): [R]D +42° (c ) 0.16); IR (CCl4) 3636, 3402, 2941, 2868
cm-1; 1H NMR (C6D6) 1.26-1.50 (2H, m), 1.56-1.70 (13H, m),
2.33-2.40 (1H, m), 2.77-2.80 (1H, m), 3.16 (3H, s), 3.49-3.60
(5H, m), 3.76-3.79 (1H, m); 13C NMR (C6D6) 22.46 (t), 23.72
(t), 27.28 (t), 29.79 (t), 30.52 (t), 30.70 (t), 32.91 (t), 55.80 (q),
62.49 (t), 62.76 (t), 70.28 (d), 73.44 (d), 78.44 (d); MS (EI) m/z
(rel intensity) 247 ([M + H]+, 3), 214 ([M - MeOH]+, 2), 196
(27), 178 (6), 162 (10), 155 (32), 141 (26), 129 (100). Anal. Calcd
for C13H26O4: C, 63.37; H, 10.64. Found: C, 63.07; H, 10.96.
R ea ct ion of 1-(3′-Hyd r oxyp r op yl)-1,2,3,6-t et r a d eoxy-
6-(3′′-h yd r oxyp r op yl)-4-O-m eth yl-r-D-er yth r o-h exop yr a -
n ose (32) w ith DIB/I2. A solution of alcohol 32 (13 mg, 0.053
mmol) in dry CCl4 (1.5 mL) containing DIB (27 mg, 0.063
mmol) and iodine (18 mg, 0.053 mmol) under nitrogen was
stirred at room temperature for 30 min. The reaction mixture
was then poured into aqueous saturated Na2S2O3 and ex-
tracted with Et2O (previously filtered through K2CO3). The
organic extracts were dried over Na2SO4, concentrated, and
chromatographed on basic aluminum oxide 60 (70-230 mesh
ASTM) Merck, activity grade I (hexanes-Et2O, 50:50) to give
33 (7.7 mg, 60%): 1H NMR (C6D6) 1.45-1.60 (8H, m), 1.74-
1.78 (2H, m), 1.96-2.00 (4H, m), 2.14 (1H, m), 2.91 (1H, ddd,
J ) 1.3, 9.2, 9.2 Hz), 3.21 (3H, s), 3.50 (2H, t, J ) 6.1 Hz),
3.82 (1H, ddd, J ) 5.3, 8.0, 8.0 Hz), 3.88 (1H, ddd, J ) 5.8,
7.9, 7.9 Hz), 3.96 (1H, ddd, J ) 2.3, 9.1, 9.1 Hz); 13C NMR
(C6D6) 22.16 (t), 24.06 (t), 25.75 (t), 31.97 (t), 32.65 (t), 33.17
(t), 37.30 (t), 55.85 (q), 62.68 (t), 66.88 (t), 73.22 (d), 79.38 (d),
105.10 (s). Anal. Calcd for C13H24O4: C, 63.90; H, 9.90.
Found: C, 64.12; H, 9.78.
(5S)-1-[3′-(p -Nit r ob en zoyl)p r op yl]-1,2,3-t r id eoxy-4-O-
m et h yl-r-D-glycer o-p en t op yr a n ose-5-sp ir o-2′′-t et r a h y-
d r op yr a n (36). To a solution of the alcohol 35 (3 mg, 0.012
mmol) in CH2Cl2 (0.1 mL) were added p-nitrobenzoyl chloride
(6 mg, 0.032 mmol) and dry pyridine (4 µL), and the mixture
was stirred at room temperature for 14 h. The reaction
mixture was poured into ice-water and extracted with EtOAc.
The organic extracts were washed with dilute HCl (10%) and
aqueous saturated NaHCO3, dried over Na2SO4, and concen-
trated under reduced pressure. Chromatography (hexanes-
EtOAc 85:15) gave the p-nitrobenzoyl derivative 36 (4.7 mg,
97%) which crystallized from MeOH: mp 82.0-82.3 °C; 1H
NMR (C6D6) 1.19-2.05 (13H, m), 2.35 (1H, br d, J ) 13.0 Hz),
2.99 (1H, t, J ) 2.7 Hz), 3.13 (3H, s), 3.57-3.71 (3H, m), 4.21-
4.30 (2H, m), 7.71 (2H, d, J ) 9.0 Hz), 7.80 (2H, d, J ) 9.1
Hz).
Rea ction of (5S)-1-(3′-Hyd r oxyp r op yl)-1,2,3-tr id eoxy-
4-O-m eth yl-r-D-glycer o-pen topyr an ose-5-spir o-2′′-tetr ah y-
d r op yr a n (35) w ith DIB/I2. A solution of alcohol 35 (20 mg,
0.082 mmol) in dry cyclohexane (5 mL) containing DIB (32 mg,
0.099 mmol) and iodine (21 mg, 0.082 mmol) under nitrogen
was stirred at room temperature for 140 min. The reaction
mixture was then poured into aqueous saturated Na2S2O3 and
extracted with Et2O (previously filtered through K2CO3). The
organic extracts were dried over Na2SO4, concentrated, and
chromatographed on basic aluminum oxide 60 (70-230 mesh
ASTM) Merck, activity grade I (n-pentane-Et2O, 85:15) to give
37 (11.6 mg, 58%)and 38 (4 mg, 20%). Compound 37: [R]D
+38.6° (c ) 0.18); IR (CCl4) 2931, 1618, 1440, 1378, 1207, 1121
1
cm-1; H NMR (C6D6) 1.41-1.55 (1H, m), 1.59-1.66 (6H, m),
1.76 (1H, dddd, J ) 13.6, 3.7, 3.7, 3.7 Hz), 2.00-2.09 (2H, m),
2.14 (1H, dd, J ) 8.0, 8.3 Hz), 2.26 (1H, ddd, J ) 13.3, 13.3,
4.0 Hz), 2.36 (1H, br d, J ) 13.3 Hz), 2.67 (1H, m), 3.18 (3H,
s), 3.22 (1H, dd, J ) 2.8, 3.1 Hz), 3.79-3.89 (2H, m), 4.07-
4.15 (2H, m); 13C NMR (C6D6) 19.1 (2 × t), 24.7 (t), 26.3 (t),
28.4 (t), 33.4 (t), 40.1 (t), 56.6 (q), 61.1 (t), 69.0 (t), 79.1 (d),
97.3 (s), 106.3 (s); MS (EI) m/z (rel intensity) 243 ([M + H]+,
12), 242 (M+, 16), 241 ([M - H]+, 20), 225 (35), 211 (8), 209
(16), 193 (16), 142 (31), 84 (100). Anal. Calcd for C13H22O4:
C, 64.44; H, 9.15. Found: C, 64.68; H, 8.78. Compound 38:
[R]D +22.2° (c ) 0.18); 1H NMR (C6D6) 1.28-1.68 (6H, m),
1.84-2.03 (6H, m), 2.17 (1H, ddd, J ) 2.7, 7.6, 7.6 Hz), 2.48
(1H, br d, J ) 7.7 Hz), 3.12 (1H, dd, J ) 3.9, 9.5 Hz), 3.38
(5S)-1-[3′-(ter t-Bu tyldiph en ylsilyl)pr opyl]-1,2,3-tr ideoxy-
4-O-m eth yl-r-D-glycer o-pen topyr an ose-5-spir o-2′′-tetr ah y-
d r op yr a n (34). A solution of the alcohol 31 (50 mg, 0.103
mmol) in dry CCl4 (5 mL) containing DIB (40 mg, 0.124 mmol)
and iodine (13 mg, 0.051 mmol) under nitrogen was stirred at
room temperature for 90 min. The reaction mixture was then
poured into aqueous saturated Na2S2O3, extracted with CH2-
Cl2, dried over Na2SO4, and concentrated. Chromatotron
chromatography of the residue (hexanes-EtOAc, 97:3) yielded

Chiral Dispiroacetals from Carbohydrates
J . Org. Chem., Vol. 63, No. 7, 1998 2261
(3H, s), 3.58-3.63 (1H, m), 3.70 (1H, ddd, J ) 7.9, 7.9, 7.9
Hz), 3.99 (1H, ddd, J ) 4.4, 8.2, 8.2 Hz), 4.06 (1H, ddd, J )
3.0, 11.0, 11.0 Hz); 13C NMR (C6D6) 1.91 (t), 23.2 (t), 24.7 (t),
26.1 (t), 29.1 (t), 32.5 (t), 38.4 (t), 58.0 (q), 61.5 (t), 68.0 (t),
81.9 (d), 98.0 (s), 106.8 (s). Anal. Calcd for C13H22O4: C, 64.44;
H, 9.15. Found: C, 64.21; H, 8.89.
experiments. A.M. thanks the Ministerio de Educacio´n
y Cultura, Spain, for a fellowship.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic details for 15 (8 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
Ack n ow led gm en t. This work was supported by the
Investigation Programme PB96-1461 of the Direccio´n
General de Investigacio´n Cient´ıfica y Te´cnica. We are
grateful to Dr. J . A. Gav´ın for assistance with NMR
J O972023A