Synthesis of mono- and dihydroxylated furanoses, pyranoses, and an oxepanose for the preparation of natural product analogue libraries

Article abstract of DOI:10.1021/jo050558v

Numerous biologically active natural products contain furanoses and pyranoses with mono- and dihydroxylated substituents. However, much of the structure-activity studies on such molecules is gathered on the aglycons without attention to the corresponding carbohydrate components. Consequently, there are few synthetic procedures that enable the rapid preparation of mono- and dihydroxyfuranoses and mono- and dihydroxypyranoses and no report for a 3,4-dihydroxyoxepanose. In this article we report the practical synthesis of orthogonally protected five-, six-, and seven-membered carbohydrate derivatives. The succinct manner in which these molecules were synthesized allows the rapid preparation of analogues aimed at discovering the role of ring size and individual hydroxyl moieties on the pyranose skeleton.

Full text of DOI:10.1021/jo050558v

Synthesis of Mono- and Dihydroxylated Furanoses, Pyranoses, and
an Oxepanose for the Preparation of Natural Product Analogue
Libraries
Xiao Ming Yu, Huijong Han, and Brian S. J. Blagg*
Department of Medicinal Chemistry and The Center for Protein Structure and Function, The University
of Kansas, 1251 Wescoe Hall Dr., Malott Hall 4070, Lawrence, Kansas 66045-7564
bblagg@ku.edu
Received March 18, 2005
Numerous biologically active natural products contain furanoses and pyranoses with mono- and
dihydroxylated substituents. However, much of the structure-activity studies on such molecules
is gathered on the aglycons without attention to the corresponding carbohydrate components.
Consequently, there are few synthetic procedures that enable the rapid preparation of mono- and
dihydroxyfuranoses and mono- and dihydroxypyranoses and no report for a 3,4-dihydroxyoxepanose.
In this article we report the practical synthesis of orthogonally protected five-, six-, and seven-
membered carbohydrate derivatives. The succinct manner in which these molecules were
synthesized allows the rapid preparation of analogues aimed at discovering the role of ring size
and individual hydroxyl moieties on the pyranose skeleton.
Introduction
aglycons,11,12 specific interactions with their biological
target,13 and even substrates for subsequent biological
activation/modification.14 Despite their essential roles,
very little attention has been paid toward enhancing their
drug discovery potential in comparison to their aglycon
counterparts. It is likely that alterations to the pyranose
ring will have significant effects on the biological activi-
ties manifested by these natural products. These effects
may include altered absorption, solubility, lability, and
interactions with a specific biological target. In the latter
case, it is reasonable to suggest that ring-expanded or
-contracted analogues will realign the accompanying
hydroxyl moieties into regions of the binding pocket that
may result in either increased or decreased affinity. On
the other hand, removal of one hydroxyl group may
abolish or attenuate interactions with the cognate recep-
tor. Considering the potential effects that can arise from
pyranose modifications, it was surprising to realize that
practical methods for the preparation of ring-expanded,
Thousands of natural products bearing carbohydrates
have been isolated from nature, and many of these
molecules have impressive biological activities that are
severely compromised by removal of the sugar moieties.1-6
Etoposide,7 bleomycin,8,9 and novobiocin10 are three such
molecules that contain substituted pyranoses and are
clinically used for the treatment of cancer (Figure 1).
The carbohydrate groups in many of these natural
products provide increased solubility as compared to their
(1) Weymouth-Wilson, A. C. Nat. Prod. Rep. 1997, 14, 99.
(2) Thorson, J. S.; Hosted, T. J.; Jiang, J. Q.; Biggins, J. B.; Ahlert,
J. Curr. Org. Chem. 2001, 5, 139.
(3) Nicolaou, K. C.; Mitchell, H. J. Angew. Chem., Int. Ed. 2001,
40, 1576.
(4) Carbohydrates in Chemistry and Biology; Ernst, B., Hart, G. W.,
Sinay, P., Eds.; Wiley-VCH: New York, 2000.
(5) Glycochemistry. Principles, Synthesis and Applications; Wong,
P. G., Bertozzi, C. P., Eds.; Marcel Dekker Inc.: New York, 2001.
(6) Vogel, P. In Glycoscience; Fraser-Reid, B. O., Tatsuta, K., Thiem,
J., Eds.; Springer: Berlin, Germany, 2001; Vol. 2, p 1023.
(7) Meresse, P.; Dechaux, E.; Monneret, C.; Bertounesque, E. Curr.
Med. Chem. 2004, 11, 2443.
(11) Lerchen, H. G.; von dem Bruch, K. J. Prakt. Chem. (Weinhaim,
Ger.) 2000, 342, 753.
(8) Ramotar, D.; Wang, H. J. Curr. Genet. 2003, 43, 213.
(9) Huang, L. R.; Xie, Y.; Lown, J. W. Expert Opin. Ther. Pat. 1996,
6, 893.
(10) Larsen, A. K.; Eseargueil, A. E.; Skladanowski, A. Pharmacol.
Ther. 2003, 99, 167.
(12) Willey, K. P. Hum. Reprod. Update 1999, 5, 330.
(13) Gabius, H. J.; Siebert, H. C.; Andre, S.; Jimenez-Barbero, J.;
Rudiger, H. Chembiochem 2004, 5, 741.
(14) Yarema, K. J.; Mahal, L. K.; Bruehl, R. E.; Rodriguez, E. C.;
Bertozzi, C. R. J. Biol. Chem. 1998, 273, 31168.
10.1021/jo050558v CCC: $30.25 © 2005 American Chemical Society
Published on Web 05/28/2005
J. Org. Chem. 2005, 70, 5599-5605
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Yu et al.
FIGURE 2. Pyranose analogues.
Not only does sugar 4 represent a pyranose derivative,
but it can also be envisioned as a ring-expanded analogue
of ribose. The 7-benzyloxy-3,4-isopropylidene protected
derivative of sugar 4 was prepared from lactone 13, which
in turn was prepared by known methods from benzyl (R)-
glycidyl ether 12, Scheme 1.17,18 Dihydroxylation of the
R,â-unsaturated lactone provided the corresponding diol
14 in good yield and with complete diastereoselectivity.
The resulting diol was protected as the acetonide, 15,
before reduction of the lactone with diisobutylaluminum
hydride to give 16 as a sole anomer. It is well-known that
hemiacetals of this type can be activated in the presence
of such protecting groups and coupled with requisite
alcohols or phenols to produce the corresponding sugar-
derived products.19-22 Afterward, these protecting groups
can be removed without affecting the glycosidic linkage
and thus providing orthogonally protected precursors to
the desired compounds.
SCHEME 1
FIGURE 1. Clinically used pyranose-containing drugs.
ring-contracted, and des(hydroxyl) variants of the pyra-
nose skeleton remain largely unreported.15,16 In this
article we describe the synthesis of protected hydroxyl-
substituted furanoses, pyranoses, and an oxepanose as
precursors for the assembly of carbohydrate-containing
natural products as a potential application toward elu-
cidation of structure-activity relationships for 3,4-dihy-
droxypyranoses.
Results and Discussion
The protected variant of sugar 5 was synthesized from
2-benzyloxy-5,6-dihydro-2H-pyran (18), which originated
from 3,4-dihydro-2H-pyran (17), by treatment with
phenylselenium chloride and benzyl alcohol, followed by
oxidation and elimination (Scheme 2).23,24 The resulting
olefin was oxidized with osmium tetroxide to furnish diol
Pyranose Derivatives. In total, eight derivatives of
pyranose were envisioned to represent both ring-ex-
panded and ring-contracted analogues as shown in Figure
2, of which four were six-membered cyclic acetals con-
taining hydroxyl replacements at either the 3-, 4-, and/
or 6-positions (4-7). A ring-expanded analogue was
prepared in the form of the oxepanose derivative, 8.
Likewise, ring-contracted furanose analogues 9-11 were
also synthesized. The protected variants of these com-
pounds were prepared so that they can be used directly
for subsequent coupling with requisite alcohols/phenols
to afford natural product analogues.
(17) Ogasawara, K.; Takahashi, M.; Ohizumi, M. Jpn. Kokai Tokkyo
Koho JP 11240877, 1999.
(18) Lai, M. T.; Oh, E.; Shih, Y.; Liu, H. W. J. Org. Chem. 1992, 57,
2471.
(19) Yu, X. M.; Shen, G.; Blagg, B. S. J. J. Org. Chem. 2004, 69,
7375.
(20) Mitsunobu, O. Synthesis 1981, 1981, 1.
(21) Audia J. E.; Boisvert L.; Patten A. D.; Villalobos A.; Danishefsky
S. J. J. Org. Chem. 1989, 54, 3738.
(22) Nguyen, H. M.; Chen, Y.; Duron, S. G.; Gin, D. Y. J. Am. Chem.
Soc. 2001, 36, 8766.
(15) Ahmed, M. M.; Berry, B. P.; Hunter, T. J.; Tomcik, D. J.;
O’Doherty, G. A. Org. Lett. 2005, 7, 745.
(16) DeMatteo, M. P.; Snyder, N. L.; Morton, M.; Baldisseri, D. M.;
Hadad, C. M.; Peczuh, M. W. J. Org. Chem. 2005, 70, 24.
(23) Vasiler, A.; Engman, L. J. Org. Chem. 2000, 65, 2151.
(24) Calvani, F.; Crotti, P.; Gardelli, C.; Pineschi, M. Tetrahedron
1994, 50, 12999.
5600 J. Org. Chem., Vol. 70, No. 14, 2005

Mono- and Dihydroxylated Furanoses and Pyranoses
19.25 In the case of bleomycin and novobiocin, the
pyranose moiety contains a carbamate in lieu of the free
alcohols. Unfortunately, there is no method for the
selective carbamoylation of compounds containing mul-
tiple hydroxyl groups. However, it is well precedented
that treatment of cyclic carbonates with methanolic
ammonia can produce carbamate products in good yields
and with reasonable regioselectivity.26 Alternatively,
cyclic carbonates can be removed by treatment with
triethylamine and methanol to afford the free alcohols.27
These conditions are suitable for deprotection/modifica-
tion of the cyclic carbonate after subsequent coupling of
the hemiacetal to the requisite hydroxyl group. Because
of these properties, the cyclic carbonate was chosen as a
versatile protecting group for various sugar derivatives
prepared in this article. As such, the diol was treated
with 1,1′-carbonyldiimidazole to afford the cyclic carbon-
ate product, 20.28 Hydrogenolysis of the benzyloxy acetal
provided the protected analogue of sugar 5, 21.
treatment with p-toluenesulfonic acid, provided 28, which
was reduced with diisobutylaluminum hydride to furnish
the racemic hemiacetal, 29.
SCHEME 4
Oxepanose Analogue. The cyclic seven-membered
ring diol 8 was prepared by a more conventional method
utilizing ring-closing metathesis to provide the cyclic
olefinic product. 4-Penten-1-ol (30) was treated with
benzyloxy allene 31, which in the presence of palladium
provided the linear benzyl-protected hemiacetal 32
(Scheme 5).31 Ring-closing metathesis using Grubb’s
second-generation catalyst32 provided the unsaturated
seven-membered ring 33. Oxidation of the alkene with
osmium tetroxide resulted in anti-dihydroxylation to give
34, which was converted to the cyclic carbonate before
removal of the benzyl group to furnish a racemic mixture
of 36.
SCHEME 2
SCHEME 5
Dihydropyran 17 was also a suitable reagent for the
preparation of protected sugar derivative 24 (Scheme 3).
As such, the cyclic enol ether was treated with m-
chloroperoxybenzoic acid in a solution of benzyl alcohol
to afford the corresponding benzyloxy acetal 22.29 Ben-
zoylation of the secondary alcohol, followed by hydro-
genolysis of the benzyl ether, afforded the protected
racemic sugar analogue 24.
SCHEME 3
Furanose Derivatives. Novobiocin competitively binds
to a nucleotide-binding site in the C-terminus of Hsp90
versus ATP.33 Therefore, one can propose that the noviose
component of novobiocin may be interacting with Hsp90
as a surrogate for the ribose ring. Consequently, it may
prove valuable to prepare furanose derivatives that
project hydroxyl groups into the recognition motif that
normally binds the ATP ribose ring.
To prepare the protected sugar analogue of 9, dihy-
drofuran was oxidized to the olefinic benzyloxy-acetal
38,34 which was further oxidized with catalytic osmium
tetroxide and stoichiometric 4-methylmorpholine N-oxide
The triisopropylsilyl ether protected version of sugar
7 was prepared from ethyl 5-benzyloxy-3-hydroxypen-
tanoate (25, Scheme 4).30 Conversion of the free alcohol
into the silyl ether 26 was accomplished in high yield.
Removal of the benzyl-protecting group, followed by
SCHEME 6
(25) Schroder, M. Chem. Rev. 1980, 80, 187.
(26) Shen, G.; Yu, X. M.; Blagg, B. S. J. Bioorg. Med. Chem. Lett.
2004, 14, 5903.
(27) Ko, S. Y. J. Org. Chem. 1995, 60, 6250.
(28) Musicki, B.; Periers, A.-M.; Laurin, P.; Ferroud, D.; Benedetti,
M. Bioorg. Med. Chem. Lett. 2000, 10, 1695.
(29) Cox, P.; Mahon, M. F.; Molley, K. C.; Lister, S.; Gallagher, T.
Tetrahedron Lett. 1989, 30, 2437.
(30) Lee, B. H.; Biswas, A.; Miller, M. J. J. Org. Chem. 1986, 51,
106.
J. Org. Chem, Vol. 70, No. 14, 2005 5601

Yu et al.
(Na2SO4), filtered, and concentrated. The residue was purified
by chromatography (SiO2, 50% EtOAc in hexanes) to afford
14 (850 mg, 74% yield) as a colorless oil: [R]25D +15.7 (c 0.92,
CH2Cl2); 1H NMR (CDCl3, 400 MHz) δ 7.26-7.10 (m, 5H), 4.75
(ddd, J ) 11.1, 8.2, 3.7 Hz, 1H), 4.62 (br s, 1H), 4.44 (d, J )
11.8 Hz, 1H), 4.38 (d, J ) 11.8 Hz, 1H), 4.21 (m, 1H), 4.16 (br
s, 1H), 4.03 (d, J ) 4.9 Hz, 1H), 3.99 (d, J ) 4.9 Hz, 1H), 3.53
(dd, J ) 3.4 Hz, 11.0 Hz, 1H), 3.39 (dd, J ) 3.7, 11.0 Hz, 1H),
2.20-1.90 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 174.4, 138.0,
128.9 (2C), 128.3, 128.1 (2C), 77.5, 74.0, 71.4, 70.8, 66.4, 30.3;
IR (film) νmax 3433, 3421, 2924, 2864, 1734, 1454, 1367, 1231,
1192, 1101, 1047, 739, 698, 667 cm-1; HRMS (ESI+) m/z
275.0896 (M + Na, C13H16O5Na1 requires 275.0895).
to afford the corresponding diol, 39 (Scheme 6). Once
again, the diol was protected as the carbonate before
removal of the benzyl group by hydrogenolysis to give
racemic 41.
Triisopropylsilyl ether protected 2-hydroxyfuranose 44
was prepared from commercially available 2-hydroxy-
butyrolactone (42) by protection of the free hydroxyl
group, followed by reduction of the lactone as shown in
Scheme 7.
SCHEME 7
(3aR,6S,7aR)-6-(Benzyloxymethyl)-2,2-dimethyl-dihy-
dro-3aH-[1,3]dioxolo[4,5-c]pyran-4(6H)-one (15). 2,2-Di-
methoxypropane (2.25 mL 29.8 mmol) was added to a solution
of 14 (900 mg, 3.57 mmol) in acetone (14 mL). p-Toluene-
sulfonic acid (15.6 mg, 0.08 mmol) was added to the solution,
which was stirred at 25 °C for 2 h. The solvent was removed
in vacuo, and saturated aqueous NaHCO3 (50 mL) was added.
The aqueous layer was extracted with EtOAc (3 × 50 mL),
and the combined organic layers were dried (Na2SO4), filtered,
and concentrated to afford 15 (650 mg, 65% yield) as a colorless
oil: [R]25D +36.0 (c 0.1, CH2Cl2); 1H NMR (CDCl3, 400 MHz) δ
7.29-7.12 (m, 5H), 4.67 (m, 1H), 4.57 (m, 1H), 4.48 (m, 3H),
3.59 (dd, J ) 10.9, 3.7 Hz, 1H), 3.53 (dd, J ) 10.9, 4.4 Hz,
1H), 2.02-1.85 (m, 2H), 1.40 (s, 3H), 1.27 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 168.5, 138.0, 128.9 (2C), 128.3, 128.2 (2C),
111.0, 74.7, 74.0, 73.2, 72.0, 71.6, 30.9, 26.5, 24.5; IR (film)
νmax 2935, 1749, 1456, 1375, 1261, 1209, 1070, 1040, 737, 698,
677 cm-1; HRMS (ESI+) m/z 315.1205 (M + Na, C16H20O5Na1
requires 315.1208).
TBS-protected 3-hydroxyfuranose 48 was prepared
from methyl 3,4-dihydroxybutanoate, 45 (Scheme 8).35
Treatment of the diol with p-toluenesulfonic acid resulted
in formation of the corresponding 2-hydroxylactone 46.
Protection of the hydroxyl substituent, followed by reduc-
tion of the lactone, provided the corresponding hemiacetal
48.
SCHEME 8
(3aR,6S,7aR)-6-(Benzyloxymethyl)-2,2-dimethyl-tet-
rahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-ol (16). Compound
15 (480 mg, 1.83 mmol) was dissolved in CH2Cl2 (15 mL) before
diisobutylaluminum hydride (1.63 mL, 1 M in hexanes, 1.63
mmol) was added dropwise at -78 °C. The resulting solution
was stirred at -78 °C for 2 h before EtOAc (20 mL) was added.
After the solution was warmed to 25 °C, saturated aqueous
sodium potassium tartrate (15 mL) was added, and the
heterogeneous solution was stirred for 30 min. The mixture
was extracted with EtOAc (3 × 30 mL), and the combined
organic layers were washed with saturated aqueous NaCl (50
mL), dried (Na2SO4), filtered, and concentrated. The residue
was purified by chromatography (SiO2, 40% EtOAc in hexanes)
Conclusion
Numerous natural products contain modified pyranose
rings, and it is important that synthetic procedures are
available for the preparation of analogues that can unveil
structure-activity relationships with regards to the
carbohydrate functionality. In this article we provide
practical methods for the construction of eight ortho-
gonally protected pyranose analogues that are suitable
for coupling in an effort to elucidate structure-activity
relationships for the pyranose moiety. Although many
of these compounds were prepared in racemic fashion, it
is likely that the utilization of Sharpless’ asymmetric
dihydroxylation procedure will afford enantioenriched
products.
to afford 16 (350 mg, 73% yield) as colorless oil: [R]25 -40.0
D
1
(c 0.42, CH2Cl2); H NMR (CDCl3, 400 MHz) δ 7.32-7.18 (m,
5H), 4.80 (dd, J ) 5.5 Hz, 3.5 Hz, 1H), 4.53 (d, J ) 12.1 Hz,
1H), 4.49 (d, J ) 12.1 Hz, 1H), 4.40 (m, 1H), 3.97 (m, 1H),
3.81 (t, J ) 5.6 Hz, 1H), 3.55 (d, J ) 3.5 Hz, 1H), 3.47-3.38
(m, 2H), 1.92-1.84 (m, 2H), 1.44 (s, 3H), 1.30 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 138.2, 128.9 (2C), 128.2, 128.1 (2C), 109.6,
95.9, 76.0, 73.9, 72.7, 72.1, 69.5, 28.6, 28.0, 26.0; IR (film) νmax
3420, 2986, 2934, 2894, 2872, 1454, 1369, 1251, 1236, 1217,
1161, 1095, 1047, 738, 698 cm-1; HRMS (ESI+) m/z 317.1368
(M + Na, C16H22O5Na1 requires 317.1365).
Experimental Section
(3R,4R,6S)-6-(Benzyloxymethyl)-3,4-dihydroxytetrahy-
dropyran-2-one (14). Osmium tetroxide (24.17 mg, 0.128
mmol) was added to a solution of 13 (1.0 g, 4.6 mmol) in H2O
(8 mL) and acetone (8 mL). The mixture was stirred at 25 °C
for 15 min before the addition of 4-methylmorpholine N-oxide
(1.23 g, 10.5 mmol). The homogeneous solution was stirred at
25 °C until 13 was consumed (∼4 h) as evidenced by TLC. H2O
(80 mL) was added, and the aqueous layer was extracted with
EtOAc (3 × 80 mL). The combined organic layers were dried
2-(Benzyloxy)-tetrahydro-2H-pyran-3,4-diol (19). Os-
mium tetroxide (0.1 mL, 20 mg/mL in toluene, 0.007 mmol)
was added to a solution of 18 (1.6 g, 9.2 mmol) and 4-meth-
ylmorpholine N-oxide (2.3 g, 20 mmol) in acetone (10 mL) and
H2O (10 mL). The mixture was stirred at 25 °C for 14 h, diluted
with H2O (200 mL) and extracted with EtOAc (3 × 100 mL).
The combined organic layers were dried (Na2SO4), filtered, and
concentrated. The residue was purified by chromatography
(SiO2, 50% EtOAc in hexanes) to afford 4 (1.70 g, 89%) as a
colorless oil: 1H NMR (CDCl3, 400 MHz) δ 7.37 (m, 5H), 4.82
(m, 2H), 4.53 (d, J ) 11.6 Hz, 1H), 4.11 (m, 1H), 3.82 (m, 2H),
3.67 (m, 1H), 2.37 (br. s, 2H), 1.84 (m, 2H); 13C NMR (CDCl3,
125 MHz) δ 137.7, 128.9 (2C), 128.4(2C), 128.3, 99.9, 70.9, 70.2,
66.6, 59.8, 30.3; IR (film) νmax 3480, 2975, 2867, 1250, 1180,
1068 cm-1; HRMS (FAB+) m/z 225.1129 (M + H+, C12H16O4
requires 225.1127).
(31) Ovaa, H.; Leeuwenburgh, M. A.; Overkleeft, H. S.; Vander-
mavel, G. A.; vanBoom, J. H. Tetrahedron Lett. 1998, 39, 3025.
(32) Chatterjee, A. K.; Grubbs, R. H. Org. Lett. 1999, 1, 1751.
(33) Marcu, M. G.; Chadli, A.; Bouhouche, I.; Catelli, M.; Neckers,
L. M. J. Biol. Chem. 2000, 275, 37181.
(34) Crotti, P.; Dibussolo, V.; Favero, L.; Macchia, F.; Pineschi, M.
Eur. J. Org. Chem. 1943, 8, 1675.
(35) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Woerpel, K. A. J.
Am. Chem. Soc. 1999, 121, 12208.
5602 J. Org. Chem., Vol. 70, No. 14, 2005

Mono- and Dihydroxylated Furanoses and Pyranoses
4-(Benzyloxy)-tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-
2-one (20). A solution of 19 (1.53 g, 7.3 mmol) and 1,1-carbonyl
diimidazole (1.95 g, 12 mmol) in 1,2-dichloroethane (20 mL)
was heated at reflux for 8 h. The mixture was cooled to 25 °C,
diluted with EtOAc (50 mL), and washed with water (3×100
mL). The organic layer was dried (Na2SO4), filtered, and
concentrated. Purification by chromatography (SiO2, 25%
EtOAc in hexanes) afforded 20 (1.38 g, 81%) as a colorless oil:
1H NMR (CDCl3, 400 MHz) δ 7.37 (m, 5H), 4.97 (m, 2H), 4.82
(d, J ) 11.8 Hz, 1H), 4.60 (d, J ) 11.8 Hz, 1H), 4.54 (dd, J )
of tert-butyldiphenylsilyl chloride (412 mg, 1.5 mmol) and
methyl 5-(benzyloxy)-3-hydroxypentanoate (270 mg, 1.13 mmol)
in DMF (2 mL) at 25 °C. The resulting mixture was stirred
for 8 h, poured into H2O (20 mL), and extracted with EtOAc
(30 mL). The organic layer was washed with H2O (30 mL),
dried (Na2SO4), filtered, and concentrated. The residue was
dissolved in MeOH (6 mL), and palladium on charcoal (10%,
65 mg) was added. The resulting mixture was stirred under
H2 (1 atm) for 48 h and filtered over Celite. The eluent was
concentrated and then redissolved in chloroform (30 mL). After
p-toluenesulfonic acid (20 mg, 0.12 mmol) was added, the
mixture was stirred at 25 °C for 24 h and concentrated. The
residue was purified by chromatography (SiO2, 20% EtOAc in
hexanes) to afford 28 (220 mg, 55%) as a white solid: 1H NMR
(CDCl3, 400 MHz) δ 7.65 (m, 4H), 7.49-7.40 (m, 6H), 4.61 (m,
1H), 4.23 (m, 2H), 2.76 (m, 1H), 2.59 (m, 2H), 1.85 (m, 2H),
1.09 (s, 9H); 13C NMR (CDCl3, 125 MHz) δ 170.4, 136.0 (4C),
133.5 (2C), 130.4 (2C), 128.3 (2C), 128.2 (2C), 65.7, 65.2, 40.1,
31.4, 27.1 (3C), 19.5; IR (film) νmax 2945, 2873, 1750, 1180,
1130, 859 cm-1; HRMS (FAB+) m/z 355.1727 (M + H+,
C21H26O3Si requires 355.1729).
4-(tert-Butyldiphenylsilyloxy)-tetrahydro-2H-pyran-2-
ol (29). Diisobutylaluminum hydride (1 M in hexanes, 0.65
mL, 0.65 mmol) was added to a solution of 28 (220 mg, 0.62
mmol) in CH2Cl2 (15 mL) at -78 °C. The resulting mixture
was stirred at -78 °C for 30 min and warmed to 25 °C.
Saturated aqueous sodium potassium tartrate (20 mL) was
added, and the heterogeneous solution was stirred for 1 h. The
organic layer was separated, washed with H2O (30 mL), dried
(Na2SO4), filtered, and concentrated. The residue was purified
by chromatography (SiO2, 25% EtOAc in hexanes) to afford
29 (182 mg, 83%) as a mixture of anomers (2:1): 1H NMR
(CDCl3, 400 MHz) δ 7.69-7.66 (m, 4H major and 4H minor),
7.44-7.39 (m, 6H major and 6H minor), 5.28 (m, 1H minor),
5.04 (m, 1H major), 4.25 (m, 1H major and 1H minor), 4.18
(m, 1H minor), 3.85 (m, 2H major), 3.60 (m, 1H minor), 2.68
(br. s, 1H), 1.85 (m, 2H major), 1.68 (m, 2H major and 1H
minor), 1.45 (m, 3H minor), 1.12 (Minor, 9H), 1.09 (s, 9H
major); 13C NMR (CDCl3, 125 MHz) δ 136.1 (4C major and 4C
minor), 134.5 (major), 134.4 (minor), 133.4 (major), 133.2
(minor),130.5 (2C minor), 130.4 (2C major), 128.3 (2C minor),
128.1 (2C major), 128.0 (2C major and 2Cminor), 93.4 (minor),
93.3 (major), 67.8 (minor), 66.2 (major), 60.5 (major), 56.2
(minor), 40.6 (major), 38.3 (minor), 34.4 (major), 32.9 (minor),
27.1 (3C major and 3C minor), 19.6 (major), 19.4 (minor); IR
(film) νmax 3400, 2960, 2868, 1175, 1049, 897 cm-1; HRMS
(FAB+) m/z 357.1891 (M + H+, C21H28O3Si requires 357.1886).
2.0, 7.6 Hz, 1H), 3.87 (m, 2H), 2.29 (m, 1H), 2.04 (m, 1H); 13
C
NMR (CDCl3, 125 MHz) δ 154.5, 136.9, 129.0 (2C), 128.7,
128.5(2C), 96.0, 74.1, 72.7, 70.5, 57.0, 25.2; IR (film) νmax 2976,
2887, 1803, 1300, 1250, 1163 cm-1; HRMS (FAB+) m/z 251.0917
(M + H+, C13H14O5 requires 251.0919).
4-Hydroxy-tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-2-
one (21). Palladium on charcoal (10%, 150 mg) was added to
a solution of 20 (1.23 g, 4.9 mmol) in methanol (10 mL). The
mixture was stirred under H2 (1 atm) for 48 h and filtered
over Celite. The eluent was concentrated, and the residue was
purified by chromatography (SiO2, 50% EtOAc in hexanes) to
afford 21 (575 mg, 73%) as a mixture of anomers (4:1): 1H
NMR (CDCl3, 400 MHz) δ 5.26 (s, 1H minor), 5.16 (d, J ) 2.8
Hz, 1H major), 5.02 (m, 1H major), 4.95 (m, 1H minor), 4.62
(dd, J ) 4.0, 6.8 Hz, 1H minor), 4.51 (dd, J ) 2.8, 7.2 Hz, 1H
major), 4.20 (m, 1H minor), 3.99 (m, 2H major and 2H minor),
2.29 (m, 1H major), 2.07 (m, 1H major and 2H minor); 13C
NMR (CDCl3, 125 MHz) δ 155.0 (major and minor), 92.3
(major), 89.8 (minor), 75.0 (major), 74.3 (minor), 73.5 (major),
72.6 (minor), 57.6 (major), 55.4 (minor), 25.5 (minor), 25.1
(major); IR (film) νmax 3400, 2967, 2870, 1807, 1190, 1074 cm-1
;
HRMS (FAB+) m/z 161.0455 (M + H+, C6H8O5 requires
161.0450).
2-(Benzyloxy)-tetrahydro-2H-pyran-3-yl Benzoate (23),
Benzoic chloride (420 mg, 3 mmol) was added dropwise to a
solution of 22 (416 mg, 2 mmol) in pyridine (6 mL) at 0 °C.
The mixture was warmed to 25 °C and stirred for 8 h. H2O
(50 mL) was added and extracted with EtOAc (50 mL). The
organic layer was washed with 5% HCl (30 mL), dried (Na2-
SO4), filtered, and concentrated. The residue was purified by
chromatography (SiO2, 25% EtOAc in hexanes) to afford 23
(610 mg, 94%) as a colorless oil: 1H NMR (CDCl3, 400 MHz)
δ 8.10 (m, 2H), 7.59 (m, 1H), 7.47 (m, 2H), 7.37 (m, 5H), 5.07
(m, 1H), 4.84 (m, 2H), 4.61 (d, J ) 12.0 Hz, 1H), 3.99 (td, J )
2.8, 10.8 Hz, 1H), 3.68 (m, 1H), 2.23 (m, 1H), 2.07 (m, 1H),
1.89 (m, 1H), 1.55 (m, 1H); 13C NMR (CDCl3, 125 MHz) δ 166.1,
138.0, 133.4, 130.6, 130.1 (2C), 128.8 (2C), 128.7 (2C), 128.2
(2C), 128.1, 97.3, 69.6, 69.4, 61.3, 24.5, 21.5; IR (film) νmax 2988,
2875, 1680, 1350, 1240, 1177, 1069 cm-1; HRMS (FAB+) m/z
313.1441 (M + H+, C19H20O4 requires 313.1440).
2-Hydroxy-tetrahydro-2H-pyran-3-yl Benzoate (24).
Palladium on charcoal (10%, 60 mg) was added to a solution
of 23 (320 mg, 1 mmol) in THF (4 mL). The mixture was stirred
under H2 (1 atm) for 70 h and filtered over Celite. The eluent
was concentrated, and the residue was purified by chroma-
tography (SiO2, 35% hexanes in EtOAc) to afford 24 (180 mg,
77%) as a mixture of anomers (2:1): 1H NMR (CDCl3, 400
MHz) δ 8.10 (m, 2H major and 2H minor), 7.59 (m, 1H major
and 1H minor), 5.15 (m, 1H major), 4.94 (m, 1H major and
2H minor), 4.07 (m, 1H major and 1H minor), 3.63 (m, 1H
major and 1H minor), 3.44 (d, J ) 5.6 Hz, 1H major), 3.23 (J
) 5.6 Hz, 1H minor), 2.24 (m, 1H major and 1H minor), 1.90
(m, 2H major and 2H minor), 1.70 (m, 1H major and 1H
minor); 13C NMR (CDCl3, 125 MHz) δ 166.8 (major), 166.5
(minor), 133.6 (major and minor), 130.3 (2C major and 2C
minor), 128.8 (2C major and 2C minor), 95.0 (major), 92.3
(minor), 71.7 (major), 71.1 (minor), 63.3 (major), 62.0 (minor),
26.0 (major), 24.8 (minor), 23.2 (minor), 23.0 (major); IR (film)
νmax 3370, 2967, 2875, 1675, 1345, 1261, 1178 cm-1; HRMS
(FAB+) m/z 223.0975 (M + H+, C12H14O4 requires 223.0970).
1-((1-(Pent-4-enyloxy)allyloxy)methyl)benzene (32). A
solution of 4-pantene-1-ol (430 mg, 5 mmol), 1-benzyloxylallene
(1.33 g, 9.1 mmol), and Et3N (760 mg, 7.5 mmol) in acetonitrile
(10 mL) was added to a dry flask containing Pd(OAc)2 (56 mg,
0.25 mmol) and DPPP (103 mg, 0.25 mmol) under argon. The
resulting mixture was heated at reflux for 2 h and concen-
trated. The residue was dissolved in hexanes (50 mL), washed
with H2O (50 mL), dried (Na2SO4), filtered, and concentrated.
The residue was purified by chromatography (SiO2, 2% EtOAc
in hexanes) to afford 32 (1.1 g, 95%) as a colorless oil: 1H NMR
(CDCl3, 400 MHz) δ 7.36 (m, 5H), 5.90 (m, 2H), 5.47 (d, J )
16.0 Hz, 1H), 5.35 (d, J ) 9.2 Hz, 1H), 5.03 (m, 3H), 4.67 (d,
J ) 12.0 Hz, 1H), 4.57 (d, J ) 12.0 Hz, 1H), 3.65 (m, 1H), 3.50
(m, 1H), 2.17 (m, 2H), 1.73 (m, 2H); 13C NMR (CDCl3, 125
MHz) δ 138.6, 138.5, 135.5, 128.8 (2C), 128.1 (2C), 127.9, 119.0,
115.2, 101.3, 67.4, 65.4, 30.8, 29.3; IR (film) νmax 2927, 2873,
1272, 1176, 1112 cm-1; HRMS (FAB+) m/z 233.1542 (M + H+,
C15H20O2 requires 233.1542).
(Z)-2-(Benzyloxy)-2,5,6,7-tetrahydrooxepine (33). Grubbs
second generation catalyst (100 mg, 0.11 mmol) was added to
a solution of 32 (1.32 g, 5.6 mmol) in CH2Cl2 (100 mL). The
resulting mixture was heated at reflux for 4 h and cooled to
25 °C. The solvent was evaporated, and the residue purified
by chromatography (SiO2, 2% ethyl acetate in hexanes) to
afford 33 (820 mg, 71%) as a colorless oil: 1H NMR (CDCl3,
4-(tert-Butyldiphenylsilyloxy)-tetrahydropyran-2-
one (28). Imidazole (136 mg, 2 mmol) was added to a solution
J. Org. Chem, Vol. 70, No. 14, 2005 5603

Yu et al.
400 MHz) δ 7.36 (m, 5H), 5.88 (m, 1H), 5.66 (m, 1H), 5.24 (d,
J ) 1.2 Hz, 1H), 4.80 (d, J ) 12.0 Hz, 1H), 4.57 (d, J ) 12.0
Hz, 1H), 4.12 (m, 1H), 3.73 (m, 1H), 2.35 (m, 1H), 2.27 (m,
1H), 1.87 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ 138.3, 132.7,
131.2, 128.8 (2C), 128.4 (2C), 128.0, 100.3, 69.5, 65.0, 29.5, 26.6;
IR (film) νmax 2978, 2875, 1640, 1277, 1190, 1087 cm-1; HRMS
(FAB+) m/z 205.1235 (M + H+, C13H16O2 requires 205.1229).
white solid: 1H NMR (CDCl3, 400 MHz) δ 7.35 (m, 5H), 5.32
(s, 1H), 5.24 (dd, J ) 3.6, 6.8 Hz, 1H), 5.01 (d, J ) 6.8 Hz,
1H), 4.72 (d, J ) 11.6 Hz, 1H), 4.52 (d, J ) 11.6 Hz, 1H), 4.26
(d, J ) 11.2 Hz, 1H), 4.06 (dd, J ) 3.6, 11.2 Hz, 1H); 13C NMR
(CDCl3, 125 MHz) δ 154.3, 1376.6, 129.0 (2C), 128.7(2C), 128.6,
104.4, 83.0, 79.7, 71.0, 69.6; IR (film) νmax 2950, 2875, 1812,
1179, 1140, 1079, 1054 cm-1; HRMS (FAB+) m/z 237.0765 (M
+ H+, C12H12O5 requires 237.0763).
4-(Benzyloxy)-hexahydro-[1,3]dioxolo[4,5-c]oxepin-2-
one (35). Osmium tetroxide (0.1 mL, 4% in H2O, 0.007 mmol)
was added to a solution of 33 (820 mg, 4 mmol) and 4-meth-
ylmorpholine N-oxide (702 mg, 6.0 mmol) in acetone (4 mL)
and H2O (4 mL). The mixture was stirred at 25 °C for 12 h,
diluted with H2O (40 mL), and extracted with EtOAc (3 × 50
mL). The organic layers were combined, dried (Na2SO4),
filtered, and concentrated. The residue was dissolved in 1,2-
dichloroethane (5 mL), and 1,1-carbonyl diimidazole (486 mg,
3 mmol) was added. The resulting mixture was heated at
reflux for 14 h, diluted with EtOAc (30 mL), washed with H2O
(3 × 30 mL), dried (Na2SO4), filtered, and concentrated. The
residue was purified by chromatography (SiO2, 30% EtOAc in
hexanes) to afford 35 (720 mg, 68%) as a colorless oil: 1H NMR
(CD3CN, 400 MHz) δ 7.36 (m, 5H), 4.95 (m, 2H), 4.81 (d, J )
1.2 Hz, 1H), 4.68 (t, J ) 8.0 Hz, 1H), 4.58 (d, J ) 12.0 Hz,
1H), 4.06 (m, 1H), 3.59 (m, 1H), 2.01 (m, 1H), 1.96 (m, 1H),
1.78 (m, 1H), 1.67 (m, 1H); 13C NMR (CD3CN, 125 MHz) δ
154.5, 137.9, 128.8 (2C), 128.4 (2C), 128.2, 102.1, 79.7, 78.2,
70.4, 69.8, 29.2, 27.0; IR (film) νmax 2975, 2860, 1806, 1178,
1049 cm-1; HRMS (FAB+) m/z 265.1078 (M + H+, C14H16O5
requires 265.1076).
4-Hydroxy-hexahydro-[1,3]dioxolo[4,5-c]oxepin-2-
one (36). Palladium on charcoal (10%, 75 mg) was added to a
solution of 35 (700 mg, 2.65 mmol) in THF (5 mL). The mixture
was stirred under H2 (1 atm) for 60 h and filtered over Celite.
The eluent was concentrated, and the residue was purified by
chromatography (SiO2, 65% EtOAc in hexanes) to afford 36
(232 mg, 50%) as a mixture of anomers (3:2): 1H NMR (CDCl3,
400 MHz) δ 5.09 (d, J ) 7.6 Hz, 1H major), 5.04 (t, J ) 8.0
Hz, 1H minor), 4.99 (s, 1H minor), 4.87 (m, 1H major and 1H
minor), 4.66 (t, J ) 8.0 Hz, 1H major), 4.08 (m, 1H major and
1H minor), 3.65 (m, 1H major), 3.55 (t, J ) 10.4 Hz, 1H minor),
2.36 (m, 1H minor), 2.15 (m, 1H major), 1.96 (m, 1H major
and 2H minor), 1.81 (m, 1H major), 1.66 (m, 1H major and
1H minor); 13C NMR (CDCl3, 125 MHz) δ 154.4 (minor), 154.3
(major), 97.3 (major), 97.2 (minor), 81.0 (minor), 80.8 (major),
78.1 (major), 76.0 (minor), 70.1 (major), 69.7 (minor), 29.7
(major), 28.3 (minor), 27.1 (major), 25.1 (minor); IR (film) νmax
3400, 2973, 2868, 1806, 1179, 1082 cm-1; HRMS (FAB+) m/z
175.0610 (M + H+, C7H10O5 requires 175.0606).
2-(Benzyloxy)-tetrahydrofuran-3,4-diol (39). Osmium
tetroxide (0.2 mL, 20 mg/mL in toluene, 0.014 mmol) was
added to a solution of 38 (2.0 g, 11.3 mmol) and 4-methylmor-
pholine N-oxide (2.3 g, 20 mmol) in acetone (10 mL) and H2O
(10 mL). The mixture was stirred at 25 °C for 6 h, diluted with
H2O (200 mL), and extracted with EtOAc (3×100 mL). The
combined organic layers were dried (Na2SO4), filtered, and
concentrated. The residue was purified by chromatography
(SiO2, 60% EtOAc in hexanes) to afford 39 (1.78 g, 75%) as a
colorless oil: 1H NMR (CDCl3, 400 MHz) δ 7.44-7.42 (m, 5H),
5.16 (s, 1H), 4.73 (d, J ) 11.6 Hz, 1H), 4.55 (m, 2H), 4.13 (m,
2H), 3.87 (m, 1H), 2.92 (s, 1H), 2.71 (s, 1H); 13C NMR (CDCl3,
125 MHz) δ 137.7, 128.9 (2C), 128.4(2C), 128.3, 107.4, 76.3,
72.7, 71.3, 69.8; IR (film) νmax 3350, 2955, 2923, 1448, 1380,
1254, 1136, 1067, 993 cm-1; HRMS (FAB+) m/z 211.0972
(M + H+, C11H14O4 requires 211.0970).
4-(Benzyloxy)-tetrahydrofuro[3,4-d][1,3]dioxol-2-one
(40). A solution of 39 (1.7 g, 8.0 mmol) and 1,1-carbonyl
diimidazole (1.95 g, 12 mmol) in 1,2-dichloroethane (20 mL)
was heated at reflux for 8 h. The mixture was cooled to 25 °C,
diluted with EtOAc (50 mL), washed with H2O (3 × 100 mL),
and dried (Na2SO4). The dried solution was filtered and
concentrated, and the residue was purified by chromatography
(SiO2, 30% EtOAc in hexanes) to afford 40 (1.62 g, 86%) as a
4-Hydroxy-tetrahydrofuro[3,4-d][1,3]dioxol-2-one (41).
Palladium on charcoal (10%, 150 mg) was added to a solution
of 40 (1.5 g, 6.3 mmol) in methanol (10 mL). The mixture was
stirred under H2 (1 atm) for 40 h and filtered over Celite. The
eluent was concentrated, and the residue was purified by
chromatography (SiO2, 50% EtOAc in hexanes) to afford 41
(752 mg, 82%) as a colorless oil: 1H NMR (CDCl3, 400 MHz)
δ 5.72 (s, 1H), 5.27 (dd, J ) 3.2, 6.4 Hz, 1H), 5.01 (d, J ) 6.4
Hz, 1H), 4.23 (m, 2H), 2.74 (s, 1H); 13C NMR (CD3OD, 125
MHz) δ 155.3, 100.1, 84.0, 80.0, 70.1; IR (film) νmax 3400, 2967,
2870, 1809, 1366, 1176 cm-1; HRMS (FAB+) m/z 147.0289 (M
+ H+, C5H6O5 requires 147.0293).
3-(Triisopropylsilyloxy)-dihydrofuran-2-(3H)-one (43).
Imidazole (1.02 g, 15 mmol) was added to a solution of
triisopropylsilyl chloride (2.90 g, 15 mmol) and 2-hydroxy-
butrylactone (900 mg, 10 mmol) in DMF (5 mL) at 25 °C. The
resulting mixture was stirred for 8 h, poured into H2O (30 mL),
and extracted with EtOAc (30 mL). The organic layer was
washed with H2O (30 mL), dried (Na2SO4), filtered, and
concentrated. The residue was purified by chromatography
(SiO2, 20% EtOAc in hexanes) to afford 43 (2.17 g, 90%) as a
colorless oil: 1H NMR (CDCl3, 400 MHz) δ 4.52 (t, J ) 8.9 Hz,
1H), 4.36 (m, 1H), 4.18 (m, 1H), 2.62 (m, 1H), 2.25 (m, 1H),
1.10 (m, 21H); 13C NMR (CDCl3, 125 MHz) δ 176.1, 68.7, 65.0,
33.2, 18.1 (6C), 12.5 (3C); IR (film) νmax 2943, 2866, 1787, 1463,
1218, 1135 cm-1; HRMS (ES+) m/z 257.1733 (M + H C13H27O3-
Si requires 283.1729).
3-(Triisopropylsilyloxy)-tetrahydrofuran-2-ol (44). Di-
isobutylaluminum hydride (1 M in hexanes, 2 mL, 2 mmol)
was added to a solution of 43 (500 mg, 2 mmol) in CH2Cl2 (10
mL) at -78 °C. The mixture was stirred at -78 °C for 15 min
and warmed to 25 °C. Saturated aqueous sodium potassium
tartrate (15 mL) was added, and the heterogeneous solution
was stirred for 1 h. The organic layer was separated, washed
with H2O (30 mL), dried (Na2SO4), filtered, and concentrated.
The residue was purified by chromatography (SiO2, 25% EtOAc
in hexanes) to afford 44 (445 mg, 89%) as a mixture of anomers
(5:4): 1H NMR (CDCl3, 400 MHz) δ 5.25 (m, 1H major and
1H minor), 4.40 (m, 1H major), 4.31 (m, 1H minor), 4.05 (m,
2H major and 2H minor), 3.79 (m, 1H major), 3.02 (br. s, 1H
minor), 2.20 (m, 1H minor), 2.10 (m, 1H major), 1.91 (m, 1H
major), 1.83 (m, 1H minor), 1.15-1.03 (m, 21H major and 21H
minor); 13C NMR (CDCl3, 125 MHz) δ 103.8 (minor), 97.3
(major), 72.8 (1C major, 1C minor), 67.7 (minor), 65.1 (major),
34.1 (major), 33.5 (minor), 18.2 (6C major and 6C minor), 12.4
(3C major and 3C minor); IR (film) νmax 3420, 2943, 2866, 1463,
1126, 1058 cm-1; HRMS (ES+) m/z 283.1699 (M + Na+
C13H28O3Si requires 283.1705).
4-(tert-Butyldimethylsilyloxy)-dihydrofuran-2(3H)-
one (47). Imidazole (1.36 g, 20 mmol) was added to a solution
of tert-butyldimethylsilyl chloride (1.57 g, 10.5 mmol) and 46
(700 mg, 7 mmol) in DMF (4 mL) at 25 °C. The resulting
mixture was stirred for 8 h, poured into H2O (20 mL), and
extracted with EtOAc (30 mL). The organic layer was washed
with H2O (30 mL), dried (Na2SO4), filtered, and concentrated.
The residue was purified by chromatography (SiO2, 20% EtOAc
in hexanes) to afford 47 (1.13 g, 74%) as a colorless oil: 1H
NMR (CDCl3, 400 MHz) δ 4.62 (m, 1H), 4.38 (dd, J ) 4.8, 10.0
Hz, 1H), 4.18 (dd, J ) 2.4, 10.0 Hz, 1H), 2.70 (dd, J ) 5.4,
17.6 Hz, 1H), 2.45 (dd, J ) 2.8, 17.6 Hz, 1H), 0.89 (s, 9H),
0.09 (s, 6H); 13C NMR (CDCl3, 125 MHz) δ 176.1, 76.5, 68.5,
38.5, 26.0, 18.3, -4.4, -4.5; IR (film) νmax 2963, 2866, 1780,
1169, 1130 cm-1; HRMS (FAB+) m/z 217.1262 (M + H+
C10H20O3Si requires 217.1260).
5604 J. Org. Chem., Vol. 70, No. 14, 2005

Mono- and Dihydroxylated Furanoses and Pyranoses
4-(tert-Butyldimethylsilyloxy)-tetrahydrofuran-2-ol (48).
Diisobutylaluminum hydride (1 M in hexanes, 5 mL, 5 mmol)
was added to a solution of 47 (1.1 g, 5 mmol) in CH2Cl2 (20
mL) at -78 °C. The mixture was stirred at -78 °C for 15 min
and warmed to 25 °C. Saturated aqueous sodium potassium
tartrate (30 mL) was added, and the heterogeneous solution
was stirred for 1 h. The organic layer was separated, washed
with H2O (30 mL), dried (Na2SO4), filtered, and concentrated.
The residue was purified by chromatography (SiO2, 25% EtOAc
in hexanes) to afford 48 (965 mg, 88%) as a mixture of anomers
(5:1): 1H NMR (CDCl3, 400 MHz) δ 5.67 (m, 1H minor), 5.43
(m, 1H major), 4.60 (m, 1H minor), 4.49 (br. s, 1H), 4.11 (m,
1H minor), 4.07 (d, J ) 9.2 Hz, 1H major), 4.01 (d, J ) 12.0
Hz, 1H major), 3.91 (m, 1H major), 3.72 (m, 1H minor), 2.07
(m, 1H major and 2H minor), 0.91 (s, 9H major), 0.89 (s, 9H
minor), 0.13 (s, 6H major), 0.08 (s, 6H minor); 13C NMR (CDCl3,
125 MHz) δ 99.7 (major), 99.2 (minor), 76.5 (major), 74.8
(minor), 72.7 (major), 72.1 (minor), 44.0 (minor), 42.8 (major),
26.1 (3C major and 3C minor), 18.4 (major), 18.3 (minor), -4.3
(minor), -4.4 (minor), -4.5 (major), -4.6 (major); IR (film) νmax
3435, 2947, 2873, 1469, 1140, 1060 cm-1; HRMS (ES+) m/z
241.1239 (M + Na+ C10H22O3Si requires 241.1236).
Acknowledgment. The authors gratefully acknowl-
edge support of this project by the NIH COBRE
RR017708 and The University of Kansas Center for
Research.
Supporting Information Available: Spectra for all
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO050558V
J. Org. Chem, Vol. 70, No. 14, 2005 5605