Rearrangement of spiroacetals of the 1,6-dioxaspiro[4.5]decan-10-yl methanesulfonate type. Synthesis of cis-fused 1,6-dioxadecalins

Full text of DOI:10.1021/jo005593a

8822
J . Org. Chem. 2000, 65, 8822-8825
We wish to report here on the results obtained by
Rea r r a n gem en t of Sp ir oa ceta ls of th e
reduction with DIBALH of the R-methanosulfonate
spiroacetal derivatives that were prepared starting from
methyl 2,3,4,6-tetra-O-benzyl-R-D-glucopyranoside.
Our synthetic approach to the dioxaspiro intermediate
is outlined in Scheme 1. Our first target was the
enlargement of the side chain at C-1 of the carbohydrate,
and for this purpose we prepared the C-glucoside by the
Lewis acid-catalyzed allylation of methyl 2,3,4,6-tetra-
O-benzyl-R-D-glucopyranoside with allyltrimethylsilane,6
which afforded 2,6-anhydro-1,3,4,5-tetra-O-benzyl-7,8,9-
trideoxy-D-glycero-L-gulo-non-8-enitol in excellent yield
and stereoselection. To obtain R-C-glucosides with the
hydroxyl group at C-2 selectively deprotected, we followed
the methodology reported by Nicotra.7 This consists of
the treatment with iodine to form a cyclic iodoether that
on reductive elimination (Zn/AcOH) results in the de-
benzylation at C-2 to give 1 (Scheme 1). To transform
the double bond in the terminal alcohol, the following
group manipulations were realized: (i) protection of the
hydroxyl group at C-2 as its tert-butyldimethylsilyl ether
2 and (ii) hydroboration-oxidation of the olefin to
produce the alcohol 3. This key molecule presents the
number of carbons and the convenient functionality for
the elaboration of the dispiro compounds. Thus, the
intramolecular hydrogen abstraction reaction was achieved
by reaction of compound 3 with (diacetoxyiodo)benzene
(DIB) and iodine in cyclohexane at 20 °C yielding the
spiroacetal 4 besides its epimer at C-1 5 in 1:2 ratio and
62% yield. The structures of 4 and 5 and the configura-
tion of the spirocenters were unambiguously established
by COSY, HMQC, and HMBC experiments, the major
isomer 5 being the less stable thermodynamically. This
was also confirmed by the acid-catalyzed isomerization
of 5 to 4.5e
1,6-Dioxa sp ir o[4.5]d eca n -10-yl
Meth a n esu lfon a te Typ e. Syn th esis of
Cis-F u sed 1,6-Dioxa d eca lin s
Carmen Betancor,† Rosa L. Dorta,† Raimundo Freire,‡
Thierry Prange´,§ 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, Departamento de Quı´mica Orga´nica,
Universidad de La Laguna, Tenerife, Spain, and LURE,
Universite´ Paris-Sud, Paris, 91405 Orsay Cedex, France
esuarez@ipna.csic.es
Received J uly 31, 2000
Compounds isolated from marine sources such as
maitotoxin1 (MXT) and halichondrins2 consist mainly of
fused polycyclic ethers, a remarkable structural feature
being the presence of two sets of cis-fused ether rings:
rings A/B and F/G in the halichondrins and rings L/M
and N/O in maitotoxin.
The important biological activity of such compounds
and their complex structures make them interesting
targets in natural products chemistry.
We have recently described a new method for the
synthesis of steroidal cis- and trans-fused ditetrahydro-
pyrans by reduction with DIBALH of steroidal metha-
nosulfonates.3 We thought that an extension of this
methodology starting from more versatile and less con-
formationally restricted substrates than steroids could
give rise to the cis-fused 1,6-dioxadecalin of the type
present in the aforementioned products. The stereochem-
ical properties of carbohydrates,4 their ready availability,
and our successful previous results in the construction
of the spiroacetal intermediates5 make them suitable
starting materials.
Deprotection and subsequent mesylation of compounds
4 and 5 afforded 7 and 9, respectively, which present the
requisites to undergo the reductive rearrangement. When
compound 7 was treated with DIBALH under several
conditions the a-methanesulfonate spiroacetal derivative
was recovered unaltered. However, compound 9 was
reduced by DIBAH in CH2Cl2 at 42 °C for 76 h to give
two products 10 and 11 in a ratio of 3:1 (Scheme 2). This
sharp contrast in reactivity may originate from a more
easy binding of DIBAH with the spiro oxygens in the case
† Departamento de Qu´ımica Orga´nica, Universidad de La Laguna.
‡ Instituto de Productos Naturales y Agrobiolog´ıa.
§ LURE, Universite´ Paris-Sud.
(1) (a) Murata, M.; Iwashita, T.; Yokoyama, A.; Sasaki, M.; Yasu-
moto, T. J . Am. Chem. Soc. 1992, 114, 6594-6596. (b) Murata, M.;
Naoki, H.; Iwashita, T.; Matsunaga, S.; Sasaki, M.; Yokoyama, A.;
Yasumoto, T. J . Am. Chem. Soc. 1993, 115, 2060-2062. (c) Sasaki,
M.; Nonomura, T.; Murata, M.; Tachibana, K. Tetrahedron Lett. 1994,
35, 5023-5026.
(2) (a) Uemura, D.; Takahashi, K.; Yamamoto, T.; Katayama, C.;
Tanaka, J .; Okumura, Y.; Hirata, Y. J . Am. Chem. Soc. 1985, 107,
4796-4798. (b) Hirata, Y.; Uemura, D. Pure Appl. Chem. 1986, 58,
701-710.
(3) (a) Dorta, R. L.; Freire, R.; Mart´ın, A.; Sua´rez, E.; Prange´, T.
Tetrahedron Lett. 1995, 36, 7309-7312. (b) Betancor, C.; Dorta, R. L.;
Freire, R.; Mart´ın, A.; Prange´, T.; Sua´rez, E. J . Org. Chem. 1998, 63,
6355-6362.
(4) (a) Hanessian, S. Total Synthesis of Natural Products. The
Chiron Approach; Pergamon Press: Oxford 1983. (b) Hanessian, S.;
Rauncourt, G. Pure Appl. Chem. 1977, 49, 1201. (c) Fraser-Reid, B.;
Tom, T. F.; Sun, K. M. In Organic Synthesis, Today and Tomorrow;
Trost, B. M., Hutchinson, C. R., Eds.; Pergamon Press: Oxford, 1981.
(d) Inch, T. D. Tetrahedron 1984, 40, 3161-3213. (e) Trends in
Synthetic Carbohydrate Chemistry; Horton, D., Hawkins, L. D., Mc-
Garvey, G. J ., Eds.; American Chemical Society: Washington, DC,
1989.
1
of compound 9. The H NMR spectrum of compound 11
clearly indicates the presence of an equatorial propyl
chain in the anomeric position and hence the reduction
of the O-C(2) bond with inversion of configuration.
More interesting was the formation of the cis-1,6-
dioxadecalin 10. The structure and stereochemistry of
this compound have been established by extensive spec-
troscopic analysis and confirmed by X-ray crystallography
of its p-nitrobenzoyl derivative.8 As observed, the rings
have a cis-fusion and both adopt a double chair confor-
mation. The selective debenzylation at C-4 is noteworthy.
(6) Lewis, M. D.; Kun Cha, J .; Kishi, Y. J . Am. Chem. Soc. 1982,
104, 4976-4978.
(5) (a) Mart´ın, A.; Salazar, J . A.; Sua´rez, E. Tetrahedron Lett. 1995,
36, 4489-4492. (b) Dorta, R. L.; Mart´ın, A.; Salazar, J . A.; Sua´rez, E.;
Prange´, T. Tetrahedron Lett. 1996, 37, 6021-6024. (c) Dorta, R. L.;
Mart´ın, A.; Sua´rez, E.; Prange´, T. Tetrahedron: Asymmetry 1996, 7,
1907-1910. (d) Mart´ın, A.; Salazar, J . A.; Sua´rez, E. J . Org. Chem.
1996, 61, 3999-4006. (e) Dorta, R. L.; Mart´ın, A.; Salazar, J . A.;
Sua´rez, E.; Prange´, T. J . Org. Chem. 1998, 63, 2251-2261.
(7) Cipolla, L.; Lay, L.; Nicotra, F. J . Org. Chem. 1997, 62, 6678-
6681.
(8) The crystallographic coordinates of 12 have been deposited with
the Cambridge Crystallographic Data Centre. The coordinates can be
obtained, upon request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.
10.1021/jo005593a CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/17/2000

Notes
J . Org. Chem., Vol. 65, No. 25, 2000 8823
Sch em e 1a
this reductive debenzylation, similar ionic debenzylations
using the iodide anion as nucleophile have been de-
scribed.7,9
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined with a
hot-stage apparatus and are uncorrected. Optical rotations were
measured at the sodium line at ambient temperature in CHCl3
solutions. IR spectra were recorded in CHCl3 solutions. NMR
spectra were determined at 500 MHz for 1H and 125.7 MHz for
13C in CDCl3 unless otherwise stated, in the presence of TMS
as internal standard. Mass spectra were determined at 70 eV.
Merck silica gel 60 PF (0.063-0.2 mm) was used for column
chromatography. Circular layers of 1 mm of Merck silica gel 60
PF254 were used on a Chromatotron for centrifugally assisted
chromatography. Commercially available reagents and solvents
were analytical grade or were purified by standard procedures
prior to use.10 All reactions involving air- or moisture-sensitive
materials were carried out under a nitrogen atmosphere. The
spray reagents for TLC analysis were conducted with 0.5%
vanillin in H2SO4-EtOH (4:1) and further heating until develop-
ment of color.
a
Key: (a) TBDMSOTf, NEt3, CH2Cl2, 0 °C, 30 min, 97%; (b)
BH3‚THF, THF, 0 °C, 2h then NaOH (3 N), H2O2, rt, 30 min, 83%;
(c) DIB/I2, cyclohexane, 20 °C, 5 h, 62%; (d) TBAF, THF, rt,
overnight, 85-95%; (e) MsCl, pyridine, rt, 5-12h, 76-80%.
Sch em e 2a
2,6-An h yd r o-1,3,4-tr i-O-ben zyl-5-O-[ter t-bu tyl(d im eth yl-
)silyl]-7,8,9-tr id eoxy-D-glycer ol-L-gu lo-n on -8-en itol (2). To
a solution of 1 (106 mg, 0.22 mmol) in dry dichloromethane (7.3
mL) were added triethylamine (244 µL, 1.75 mmol) and tert-
butyldimethylsilyltrifluoromethane sulfonate (213 µL, 0.93 mmol),
and the solution was stirred under nitrogen at 0 °C for 30 min.
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 chromatography of the residue (hex-
anes-EtOAc, 97:3) gave the title compound 2 (128 mg, 0.22
mmol, 97%): [R]D ) +55 (c ) 1.2); IR 3066, 3032, 2955, 2929,
2857, 1945, 1869, 1805, 1726, 1642, 1497, 1454, 1360, 1257 cm-1
;
1H NMR δ 7.40-7.28 (13H, m), 7.11-7.10 (2H, m), 5.90 (1H,
dddd, J ) 17.1, 10.1, 6.8, 6.8 Hz), 5.16 (1H, dd, J ) 17.1, 1.5
Hz), 5.13 (1H, dd, J ) 10.2, 1.4 Hz), 4.96 (1H, d, J ) 11.4 Hz),
4.86 (1H, d, J ) 11.4 Hz), 4.81 (1H, d, J ) 10.6 Hz), 4.69 (1H, d,
J ) 12.1 Hz), 4.53 (2H, d, J ) 12.1 Hz), 4.50 (1H, d, J ) 10.6
Hz), 4.06 (1H, dd, J ) 13.5, 7.4 Hz), 3.97 (1H, dd, J ) 6.0, 6.0
Hz), 3.77 (1H, br d, J ) 10.4 Hz), 3.68 (3H, m), 2.54 (1H, dd, J
) 7.2, 7.2 Hz), 0.96 (9H, s), 0.13 (3H, s), 0.12 (3H, s); 13C NMR
δ 138.9 (C), 138.2 (C), 138.0 (C), 135.0 (CH), 128.3-127.3 (15 ×
CH), 116.7 (CH2), 83.2 (CH), 78.3 (CH), 76.4 (CH), 75.4 (CH2),
75.0 (CH2), 73.5 (CH2), 73.1 (CH), 71.1 (CH), 68.9 (CH2), 29.0
(CH2), 25.9 (3 × CH3), 17.9 (C), -4.5 (CH3), -4.7 (CH3); MS m/z
(rel intensity) 589 (M+ + 1 , <1), 497 (16), 439 (35), 391 (43),
a
Key: (a) DIBALH, CH2Cl2, 42 °C, 76 h, 72%; (b) p-nitrobenzoyl
chloride, pyridine, rt, 4 h, 90%.
Sch em e 3
349 (60), 333 (46), 271 (100); HRMS calcd for
C36H49O5Si
589.3349, found 589.3382. Anal. Calcd for C36H48O5Si: C, 73.43;
H, 8.22. Found: C, 73.13; H, 8.56.
2,6-An h yd r o-1,3,4-tr i-O-ben zyl-5-O-[ter t-bu tyl(d im eth yl-
)silyl]-7,8-d id eoxy-D-glycer ol-L-gu lo-n on itol (3). To a solution
of olefin 2 (730 mg, 1.24 mmol) in dry THF (3.5 mL) at 0 °C and
under nitrogen was added dropwise a solution of BH3‚THF
complex (3.5 mL, 3.5 mmol, 1 M in THF). After 2 h of stirring,
the excess borane was quenched carefully by adding a drop of
water. Dropwise addition of a mixture of 3 N NaOH (15 mL)
and 30% hydrogen peroxide (15 mL), removal of the cooling bath,
and continued stirring for 30 min resulted in a white heteroge-
neous mixture. The reaction mixture was then poured into ice-
water and extracted with CH2Cl2, washed with brine, dried over
Na2SO4, and concentrated in a vacuum. Chromatotron chroma-
tography of the residue (hexanes-EtOAc, 90:10, 80:20, 70:30)
yielded alcohol 3 (624 mg, 1.03 mmol, 83%): [R]D ) +28.9 (c )
0.79); IR 3638, 3502, 3066, 3032, 2955, 2929, 2857, 1945, 1869,
A plausible mechanism for the formation of these
products is proposed. In the first step, the aluminum
reagent coordinates at the tetrahydrofuran oxygen, which
is the more nucleophilic, and reduces the oxonium ion
with inversion of configuration. Then, the alkoxy inter-
mediate could undergo a transesterification of the meth-
anesulfonate group to give a more stable primary meth-
anesulfonyl derivative which is subsequently reduced
with an excess of DIBALH to give compound 11. The
mechanism proposed for the formation of compound 10
is outlined in Scheme 3. The reductive debenzylation at
C-4 is promoted by the hydride ion assisted by the
neighboring methanesulfonyl group. The alkoxy anion
could now attack the cyclic sulfate via an intramolecular
SN2 displacement with inversion of configuration to afford
10. Although we are unaware of previous precedents for
1805, 1454, 1359, 1254 cm-1 1H NMR δ 7.37-7.25 (13H, m),
;
7.09-7.07 (2H, m), 4.92 (1H, d, J ) 11.4 Hz), 4.80 (1H, d, J )
(9) Selective debenzylation: (a) Ziegler, F. E.; Wang, Y. J . Org.
Chem. 1998, 63, 426-427. (b) Ziegler, F. E.; Wang, Y. J . Org. Chem.
1998, 63, 7920-7930. (c) Nicotra, F.; Panza, L.; Russo, G. J . Org. Chem.
1997, 52, 5627-5630. (d) Rychnovsky, S. D.; Bartlett, P. A. J . Am.
Chem. Soc. 1981, 103, 3963-3964.
(10) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon Press: New York, 1988.

8824 J . Org. Chem., Vol. 65, No. 25, 2000
Notes
11.4 Hz), 4.78 (1H, d, J ) 10.7 Hz), 4.64 (1H, d, J ) 12.1 Hz),
4.53 (1H, d, J ) 12.1 Hz), 4.44 (1H, d, J ) 10.7 Hz), 3.97-3.89
(2H, m), 3.74-3.63 (5H, m), 3.56 (1H, dd, J ) 9.2, 9.0 Hz), 2.00
(1H, br s), 1.87-1.81 (2H, m), 1.71-1.67 (2H, m), 0.92 (9H, s),
0.95 (3H, s), 0.88 (3H, s); 13C NMR δ 138.8 (C), 138.1 (C), 137.8
(C), 128.3-127.3 (15 × CH), 83.1 (CH), 78.4 (CH), 77.1 (CH),
75.3 (CH2), 75.0 (CH2), 73.5 (CH2), 73.2 (CH), 71.1 (CH), 69.2
(CH2), 62.3 (CH2), 29.4 (CH2), 25.8 (3 × CH3), 20.1 (CH2), 17.9
(C), -4.6 (CH3), -4.7 (CH3); MS m/z (rel intensity) 606 (M+, <1),
549 (9), 515 (9), 441 (82), 409 (58), 351 (67), 259 (65), 243 (100);
HRMS calcd for C36H50O6Si 606.3377, found 606.3375. Anal.
Calcd for C36H50O6Si: C, 71.25; H, 8.30. Found: C, 71.26; H,
8.57.
m), 1.92-1.86 (1H, m); 13C NMR δ 138.8 (C), 138.4 (C), 138.2
(C), 128.5-127.4 (15 × CH), 107.5 (C), 84.8 (CH), 77.9 (CH), 75.3
(CH2), 74.7 (CH2), 73.6 (CH), 73.4 (CH2), 71.5 (CH), 68.8 (CH2),
68.7 (CH2), 33.6 (CH2), 24.0 (CH2); MS m/z (rel intensity) 490
(M+, 52), 399 (100), 293 (24), 275 (40), 253 (36), 240 (86), 203
(90), 181 (84); HRMS calcd for
C30H34O6 490.2355, found
490.2367. Anal. Calcd for C30H34O6: C, 73.45; H, 6.99. Found:
C, 73.34; H, 7.01.
(5S,7S,8S,9S,10R)-8,9-Bis(ben zyloxy)-7-[(ben zyloxy)m e-
th yl]-1,6-d ioxa sp ir o[4.5]d ec-10-yl Meth a n esu lfon a te (7). A
solution of the alcohol 6 (9.7 mg, 0.020 mmol) in dry pyridine
(0.5 mL) was treated at room temperature for 5 h with meth-
anesulfonyl chloride (20 µL, 0.24 mmol). Then the mixture was
poured over an aqueous solution of HCl (10%) and extracted with
CH2Cl2. The combined extracts were washed with saturated
aqueous NaHCO3 and brine, dried, filtered, and evaporated
under pressure. Chromatotron chromatography (hexanes-
EtOAc, 85:15) of the residue gave compound 7 (8.6 mg, 0.015
mmol, 76%): mp 95-96 °C (from n-pentane-ethyl ether); [R]D
+8.8 (c ) 0.26); IR 3066, 3032, 2926, 2854, 1945, 1870, 1806,
[[(5R,7S,8S,9S,10R)-8,9-Bis(b en zyloxy)-7-[(b en zyloxy)-
methyl]-1,6-dioxaspiro[4.5]dec-10-yl]oxy](tert-butyl)dimethyl-
silan e (4)an d [[(5S,7S,8S,9S,10R)-8,9-Bis(ben zyl-oxy)-7-[(ben -
zyloxy)m eth yl]-1,6-dioxaspir o[4.5]dec-10-yl]oxy](ter t-bu tyl)-
d im eth ylsila n e (5). A solution of 3 (542 mg, 0.89 mmol) in dry
cyclohexane (114 mL) containing (diacetoxyiodo)benzene (DIB)
(699 mg, 2.17 mmol) and iodine (272 mg, 1.07 mmol) was stirred
under nitrogen at 20 °C for 5 h. The reaction mixture was then
poured into a 10% aqueous sodium thiosulfate solution, extracted
with CH2Cl2, dried (Na2SO4), and concentrated in a vacuum.
Chromatotron chromatography of the residue (hexanes-EtOAc,
95:5) yielded 4 (112 mg, 0.185 mmol, 21%) and 5 (221 mg, 0.366
mmol, 41%). Compound 4: [R]D ) +22 (c ) 0.33); IR 3032, 2955,
2929, 2857, 1945, 1869, 1805, 1726, 1549, 1496, 1454, 1361, 1252
1726, 1456, 1365 cm-1 1H NMR δ 7.37-7.25 (13H, m), 7.13-
;
7.12 (2H, m), 5.03 (1H, d, J ) 11.4 Hz), 4.76 (1H, d, J ) 10.8
Hz), 4.74 (1H, d, J ) 11.4 Hz), 4.65 (1H, d, J ) 12.2 Hz), 4.62
(1H, d, J ) 10.0 Hz), 4.59 (1H, d, J ) 10.8 Hz), 4.53 (1H, d, J )
12.2 Hz), 4.06 (1H, dd, J ) 9.2, 9.2 Hz), 4.01 (1H, ddd, J ) 7.2,
7.2, 7.2 Hz), 3.95 (1H, ddd, J ) 7.4, 7.4, 7.4 Hz), 3.88 (1H, ddd,
J ) 9.8, 1.2, <1 Hz), 3.81 (1H, dd, J ) 9.2, 9.2 Hz), 3.77 (1H,
dd, J ) 10.9, 3.1 Hz), 3.66 (1H, dd, J ) 10.9, <1 Hz), 2.82 (3H,
s), 2.35-2.30 (1H, m), 2.07-2.01 (2H, m), 1.99-1.95 (1H, m);
13C NMR (50.3 MHz) δ 138.0 (C), 137.9 (C), 137.8 (C), 128.5-
127.1 (15 × CH), 106.2 (C), 81.0 (CH), 80.4 (CH), 79.1 (CH), 75.2
(CH2), 74.8 (CH2), 73.5 (CH2), 71.4 (CH), 68.9 (CH2), 68.3 (CH2),
38.6 (CH3), 33.9 (CH2), 24.0 (CH2); MS m/z (rel intensity) 477
(M+ - C7H7, 32), 472 (19), 275 (9), 273 (13), 256 (100), 245 (6),
216 (9), 203 (56); HRMS calcd for C24H29O8S 477.1583, found
477.1578. Anal. Calcd for C31H36O8S: C, 65.47; H, 6.38; S, 5.64.
Found: C, 65.46; H, 6.57; S, 5.32.
cm-1 1H NMR δ 7.39-7.22 (13H, m), 7.05-7.04 (2H, m), 4.99
;
(1H, d, J ) 12.0 Hz), 4.87 (1H, d, J ) 12.0 Hz), 4.73 (1H, d, J )
10.8 Hz), 4.66 (1H, d, J ) 12.2 Hz), 4.54 (2H, d, J ) 12.2 Hz),
4.52 (2H, d, J ) 10.8 Hz), 4.01-3.94 (2H, m), 3.88-3.84 (2H,
m), 3.77-3.64 (4H, m), 2.19 (1H, ddd, J ) 12.1, 9.3, 9.3 Hz),
2.11-2.03 (1H, m), 1.93-1.86 (2H, m), 0.93 (9H, s), 0.12 (3H,
s), 0.03 (3H, s); 13C NMR δ 139.2 (C), 138.2 (C), 138.1 (C), 128.3-
126.6 (15 × CH), 107.9 (C), 83.5 (CH), 79.1 (CH), 74.8 (CH2),
74.5 (CH2), 73.5 (CH), 73.4 (CH2), 71.0 (CH), 68.8 (CH2), 68.3
(CH2), 33.4 (CH2), 26.0 (3 × CH3), 23.8 (CH2), 18.1 (C), -3.5
(CH3), -4.5 (CH3); MS m/z (rel intensity) 604 (M+, 8), 547 (18),
513 (22), 440 (36), 439 (100), 397 (48), 331 (20), 277 (73); HRMS
calcd for C36H48O6Si 604.3220, found 604.3234. Anal. Calcd for
(5R,7S,8S,9S,10R)-8,9-Bis(ben zyloxy)-7-[(ben zyloxy)m eth -
yl]-1,6-d ioxa sp ir o[4.5]d eca n -10-ol (8). As described for the
preparation of 6. Compound 5 (181 mg, 0.30 mmol) gave after
Chromatotron chromatography (hexanes-EtOAc, 75:25) the
alcohol 8 (139 mg, 0.28 mmol, 95%): [R]D ) +21 (c ) 0.67); IR
3603, 3474, 3089, 3066, 3032, 2894, 1945, 1870, 1806, 1726,
C
36H48O6Si: C, 71.49; H, 8.00. Found: C, 71.18; H, 8.24.
Compound 5: [R]D ) 0 (c ) 0.32); IR 3032, 2955, 2929, 2857,
1945, 1869, 1805, 1726, 1454, 1361, 1252 cm-1; 1H NMR δ 7.36-
7.22 (13H, m), 7.06-7.04 (2H, m), 4.90 (1H, d, J ) 11.5 Hz),
4.85 (2H, d, J ) 11.5 Hz), 4.73 (1H, d, J ) 10.6 Hz), 4.61 (1H, d,
J ) 12.1 Hz), 4.54 (1H, d, J ) 12.1 Hz), 4.48 (1H, d, J ) 10.6
Hz), 4.04 (1H, ddd, J ) 13.8, 7.7, <1 Hz), 3.89 (1H, ddd, J )
13.6, 7.1, <1 Hz), 3.74 (1H, d, J ) 9.7 Hz), 3.72-3.66 (2H, m),
3.57 (1H, dd, J ) 9.4, 9.4 Hz), 3.47 (1H, ddd, J ) 9.9, 4.6, 2.2
Hz), 3.41 (1H, dd, J ) 9.4, 9.4 Hz), 2.15-2.10 (1H, m), 2.04-
2.00 (1H, m), 1.97-1.91 (1H, m), 0.89 (9H, s), 0.11 (3H, s), 0.05
(3H, s); 13C NMR δ 138.8 (C), 138.2 (C), 137.9 (C), 128.2-126.9
(15 × CH), 109.7 (C), 85.1 (CH), 78.6 (CH), 75.2 (CH2), 74.9
(CH2), 74.2 (CH), 73.7 (CH), 73.4 (CH2), 69.5 (CH2), 67.8 (CH2),
26.5 (CH2), 25.9 (3 × CH3), 24.4 (CH2), 18.0 (C), -4.5 (2 × CH3);
MS m/z (rel intensity) 604 (M+, 2), 547 (6), 513 (6), 455 (6), 440
(32), 439 (100), 331 (24), 277 (66); HRMS calcd for C36H48O6Si
604.3220, found 604.3224. Anal. Calcd for C36H48O6Si: C, 71.49;
H, 8.00. Found: C, 71.37; H, 8.10.
1497, 1454, 1360 cm-1 1H NMR δ 7.41-7.27 (13H, m), 7.19-
;
7.17 (2H, m), 4.93 (1H, d, J ) 11.3 Hz), 4.88 (1H, d, J ) 11.3
Hz), 4.84 (1H, d, J ) 10.7 Hz), 4.64 (1H, d, J ) 12.1 Hz), 4.55
(1H, d, J ) 12.1 Hz), 4.54 (1H, d, J ) 10.7 Hz), 4.09 (1H, dd, J
) 7.3, 7.3 Hz), 3.98 (1H, dd, J ) 7.4, 7.4 Hz), 3.79 (1H, d, J )
9.7 Hz), 3.75-3.70 (2H, m), 3.64 (1H, dd, J ) 9.3, 9.3 Hz), 3.55
(1H, dd, J ) 9.3, 9.3 Hz), 3.53-3.50 (1H, m), 2.47 (1H, br s),
2.18-2.11 (1H, m), 2.09-2.03 (1H, m), 2.00-1.92 (2H, m); 13C
NMR (50.3 MHz) δ 138.6 (C), 138.2 (C), 138.0 (C), 128.6-127.6
(15 × CH), 109.3 (C), 83.9 (CH), 78.0 (CH), 75.1 (CH2), 75.0
(CH2), 74.1 (2 × CH), 73.4 (CH2), 69.4 (CH2), 68.6 (CH2), 27.0
(CH2), 25.0 (CH2); MS m/z (rel intensity) 490 (M+, 66), 399 (64),
275 (27), 253 (41), 240 (92), 219 (71), 203 (79), 181 (100); HRMS
calcd for C30H34O6 490.2355, found 490.2350. Anal. Calcd for
C
30H34O6: C, 73.45; H, 6.99. Found: C, 73.39; H, 7.16.
(5R,7S,8S,9S,10R)-8,9-Bis(ben zyloxy)-7-[(ben zyloxy)m eth -
(5S,7S,8S,9S,10R)-8,9-Bis(ben zyloxy)-7-[(ben zyloxy)m e-
th yl]-1,6-d ioxa sp ir o[4.5]d eca n -10-ol (6). To a deoxygenated
solution of compound 4 (32 mg, 0.053 mmol) in dry THF (2 mL)
was added tetrabutylammonium fluoride (185 µL, 185 mmol, 1
M in THF), and the mixture was stirred at room temperature
overnight. The solvent was removed under reduced pressure,
and the residue was dissolved in CHCl3, washed with aqueous
saturated NaHCO3 and brine, dried over Na2SO4, and concen-
trated. Chromatotron chromatography (hexanes-EtOAc, 70:30)
gave the alcohol 6 (22.1 mg, 0.045 mmol, 85%): mp 75-76 °C
(from n-pentane-ethyl ether); [R]D ) +72 (c ) 0.91); IR 3568,
yl]-1,6-d ioxa sp ir o[4.5]d ec-10-yl Meth a n esu lfon a te (9). As
described for the preparation of 7. Alcohol 8 (52 mg, 0.11 mmol)
gave compound 9 (48 mg, 0.084 mmol, 80%): mp 90-91 °C (from
n-pentane-ethyl ether); [R]D ) 0 (c ) 0.34); IR 3066, 3032, 2893,
1
1945, 1870, 1806, 1729, 1497, 1454, 1375, 1181 cm-1; H NMR
δ 7.43-7.27 (13H, m), 7.14-7.13 (2H, m), 4.95 (1H, d, J ) 10.5
Hz), 4.80 (1H, d, J ) 10.5 Hz), 4.81 (1H, d, J ) 10.7 Hz), 4.70
(1H, d, J ) 9.8 Hz), 4.61 (1H, d, J ) 12.1 Hz), 4.52 (1H, d, J )
12.1 Hz), 4.51 (1H, d, J ) 10.7 Hz), 4.14-4.08 (1H, m), 3.98-
3.94 (1H, m), 3.73 (1H, dd, J ) 9.4, 9.4 Hz), 3.69 (2H, m), 3.67
(1H, dd, J ) 9.3, 9.3 Hz), 3.49 (1H, ddd, J ) 9.6, 3.2, 3.2 Hz),
3.03 (3H, s), 2.13-2.07 (3H, m), 2.04-1.99 (1H, m); 13C NMR
(50.3 MHz) δ 138.0 (C), 137.7 (C), 137.5 (C), 128.4-127.6 (15 ×
CH), 107.5 (C), 82.1 (CH), 81.4 (CH), 78.2 (CH), 75.7 (CH2), 75.2
(CH2), 74.0 (CH), 73.4 (CH2), 68.8 (CH2), 68.5 (CH2), 38.9 (CH3),
28.1 (CH2), 24.6 (CH2); MS m/z (rel intensity) 477 (M+ - C7H7,
20), 472 (74), 381 (16), 371 (6), 364 (8), 322 (8), 273 (41), 256
(22), 244 (31), 216 (27), 203 (100); HRMS calcd for C24H29O8S
3066, 3032, 2889, 1945, 1869, 1805, 1726, 1496, 1454, 1361 cm-1
;
1H NMR δ 7.38-7.27 (13H, m), 7.20-7.18 (2H, m), 4.91 (1H, d,
J ) 11.2 Hz), 4.87 (1H, d, J ) 11.2 Hz), 4.83 (1H, d, J ) 11.0
Hz), 4.63 (1H, d, J ) 12.2 Hz), 4.55 (1H, d, J ) 11.0 Hz), 4.52
(1H, d, J ) 12.2 Hz), 4.00-3.94 (2H, m), 3.82 (1H, ddd, J ) 9.9,
3.8, 1.8 Hz), 3.76-3.71 (2H, m), 3.68-3.63 (3H, m), 2.23 (1H,
ddd, J ) 12.3, 9.6, 7.6 Hz), 2.08-2.01 (1H, m), 2.00-1.95 (1H,

Notes
J . Org. Chem., Vol. 65, No. 25, 2000 8825
477.1583, found 477.1489. Anal. Calcd for C31H36O8S: C, 65.47;
H, 6.38; S, 5.64. Found: C, 65.55; H, 6.56; S, 5.34.
293 (100), 187 (18), 169 (36), 151 (14), 139 (31); HRMS calcd for
C
23H28O5 384.1937, found 384.1924. Anal. Calcd for C23H28O5:
R ed u ct ion of (5R,7S,8S,9S,10R)-8,9-Bis(b en zyloxy)-7-
[(ben zyloxy)m eth yl]-1,6-d ioxa sp ir o[4.5]d ec-10-yl Meth a n e-
su lfon a te (9). To a stirred solution of the â-mesyl derivative 9
(51.4 mg, 0.09 mmol) in dry CH2Cl2 (3 mL) at 42 °C under
nitrogen was added DIBALH in toluene (1 mL, 1 mmol). The
solution was stirred for 76 h, and the reaction was quenched by
careful addition of saturated aqueous NH4Cl. The mixture was
filtered through filter paper, and the residue was washed with
CH2Cl2. The combined filtrates were washed with brine, dried,
and concentrated. The residue was purified by chromatotron
chromatography (benzene-EtOAc, 95:5) to give 1-(3′,4′,6′-tri-O-
benzyl)-R-D-glucopyranosyl)-2-propane (11) (7.0 mg, 0.016 mmol,
18%) and (2R,3R,4R,4aR,8aS)-3-(benzyloxy)-2-(phenoxymethyl)-
octahydropyrano[3,2-b]pyran-4-ol (10) (18.7 mg, 0.049 mmol,
54%). Compound 11: [R]D ) +9.2 (c ) 0.52); IR 3482, 3066, 3030,
C, 71.85; H, 7.34. Found: C, 71.70; H, 7.61.
(2R,3R,4R,4a R,8a S)-3-(Ben zyloxy)-2-(p h en oxym et h yl)-
octa h yd r op yr a n o[3,2-b]p yr a n -4-yl 4-Nitr oben zoa te (12). To
a stirred solution of compound 10 (5.2 mg, 0.013 mmol) in CH2-
Cl2 (0.1 mL) and pyridine (4 µL) was added p-nitrobenzoyl
chloride (6 mg, 0.032 mmol). The solution was stirred at room
temperature for 4 h, and then the mixture was poured over an
aqueous solution of HCl (10%) and extracted with CH2Cl2. The
combined extracts were washed with saturated aqueous NaH-
CO3 and brine, dried, and evaporated under reduced pressure
to give compound 12 (6.5 mg, 0.012 mmol, 90%): mp 97-99 °C
(from n-pentane-ethyl ether); [R]D ) -27.5 (c ) 0.24); IR 2926,
2854, 1945, 1870, 1806, 1728, 1606, 1532, 1455, 1347, 1275, 1114
cm-1 1H NMR δ 8.30-8.14 (4H, m), 7.39-7.02 (10H, m), 5.14
;
(1H, dd, J ) 3.5, 9.8 Hz), 4.72 (1H, d, J ) 12.2 Hz), 4.60 (1H, d,
J ) 12.2 Hz), 4.59 (1H, d, J ) 11.3 Hz), 4.57 (1H, d, J ) 11.3
Hz), 4.12 (1H, dd, J ) 9.8, 9.8 Hz), 4.01 (1H, ddd, J ) <1, 4.0,
11.2 Hz), 3.89 (1H, d, J ) 3.4 Hz), 3.82 (1H, dd, J ) 4.7, 11.1
Hz), 3.76 (1H, dd, J ) 1.4, 11.2 Hz), 3.59 (1H, br s), 3.56 (1H,
ddd, J ) 1.4, 4.7, 9.7 Hz), 23.36 (1H, dd, J ) 11.6, 11.6 Hz),
2.09-2.05 (2H, m), 1.65-1.60 (1H, m), 1.34-1.32 (1H, m); 13C
NMR δ 164.2 (C), 150.5 (C), 138.3 (C), 137.8 (C), 135.3 (C),
130.9-123.4 (CH), 79.4 (CH), 78.2 (CH), 75.0 (CH2), 74.6 (CH),
73.4 (CH2), 73.3 (CH), 70.9 (CH), 69.1 (CH2), 68.1 (CH2), 28.0
(CH2), 20.6 (CH2); MS m/z (rel intensity) 442 (M+ - C7H7, 13),
336 (9), 169 (31), 150 (23), 139 (8), 120 (12), 105 (8), 91 (100);
HRMS calcd for C23H24NO8 442.1101, found 442.1428.
1
2869, 1945, 1869, 1805, 1723, 1454, 1270, 1094 cm-1; H NMR
δ 7.33-7.26 (15H, m), 4.57-4.47 (6H, m), 4.27 (1H, ddd, J )
3.2, 6.0, 6.0 Hz), 4.07 (1H, dd, J ) 3.0, 3.0 Hz), 4.03 (1H, dd, J
) 2.6, 4.4 Hz), 3.88 (1H, dd, J ) 4.86, 4.86 Hz), 3.62 (1H, ddd,
J ) 5.1, 8.7, 8.7 Hz), 3.60-3.54 (2H, m), 2.38 (1H, d, J ) 5.4
Hz), 1.57-1.47 (2H, m), 1.41-1.36 (2H, m), 0.91 (3H, dd, J )
7.1, 7.1 Hz); 13C NMR δ 138.0 (C), 137.6 (C), 137.5 (C), 128.4-
127.6 (15 × CH), 85.7 (CH), 84.8 (CH), 84.6 (CH), 82.0 (CH),
73.3 (CH2), 71.8 (CH2), 71.7 (CH2), 70.9 (CH), 69.8 (CH2), 35.7
(CH2), 18.8 (CH2), 14.0 (CH3); MS m/z (rel intensity) 385 (M+
-
C7H7, <1), 384 (14), 383 (62), 296 (35), 277 (35), 261 (12); HRMS
calcd for C23H29O5 385.2015, found 385.2026. Anal. Calcd for
C30H36O5: C, 75.60; H, 7.61. Found: C, 75.69; H, 7.68. Compound
10: [R]D ) -4.9 (c ) 0.69); IR 3566, 2924, 2854, 1945, 1870,
Ack n ow led gm en t. This work was supported by the
Investigation Program No. PB96-1461 of the Direccio´n
General de Investigacio´n Cient´ıfica y Te´cnica, Spain.
1806, 1729, 1454, 1114 cm-1 1H NMR δ 7.36-7.22 (10H, m),
;
4.86 (1H, d, J ) 11.1 Hz), 4.65 (1H, d, J ) 12.2 Hz), 4.59 (1H, d,
J ) 12.2 Hz), 4.57 (1H, d, J ) 11.1 Hz), 4.07-4.04 (1H, m), 3.77-
3.69 (2H, m), 3.66 (1H, ddd, J ) 8.8, 8.8, 3.7 Hz), 3.59-3.58 (1H,
m), 3.56 (1H, d, J ) 9.2 Hz), 3.46-3.45 (1H, m), 3.43-3.38 (2H,
m), 2.55 (1H, d, J ) 8.7 Hz), 2.08-1.98 (2H, m), 1.65-1.58 (2H,
m), 1.37-1.32 (1H, m); 13C NMR (50.3 MHz) δ 138.5 (C), 128.3-
127.5 (10 × CH), 78.8 (CH), 76.7 (CH), 76.6 (CH), 75.3 (CH),
74.9 (CH2), 73.4 (CH2), 71.1 (CH), 69.6 (CH2), 68.3 (CH2), 28.1
(CH2), 21.0 (CH2); MS m/z (rel intensity) 384 (M+, <1), 294 (18),
Su p p or tin g In for m a tion Ava ila ble: X-ray data for com-
pound 12, including tables of atomic coordinates, bond lengths,
and bond angles. This material is available free of charge via
the Internet at http://pubs.acs.org.
J O005593A