Mild stereoselective synthesis of fully protected 1,6-dioxaspiro[4.5]dec-3-ene derivatives of sugars

Article abstract of DOI:10.1002/1099-0690(20022)2002:3<534::aid-ejoc534>3.0.co;2-r

Perbenzylated 1,6-dioxaspiro[4.5]dec-3-ene derivatives of sugars are prepared in three steps, starting from fully protected glycono-1,5-lactones. The procedure exploits a reagent previously devised in our laboratory, the 3-C-lithiated 5,6-dihydro-1,4-dith

Full text of DOI:10.1002/1099-0690(20022)2002:3<534::aid-ejoc534>3.0.co;2-r

FULL PAPER
Mild Stereoselective Synthesis of Fully Protected 1,6-Dioxaspiro[4.5]dec-3-ene
Derivatives of Sugars
Romualdo Caputo,[a] Annalisa Guaragna,*[a] Giovanni Palumbo,[a] Silvana Pedatella,[a] and
Francesco Solla[a]
Keywords: Spiro compounds / Carbohydrates / Lactones
Perbenzylated 1,6-dioxaspiro[4.5]dec-3-ene derivatives of
hydroxypropenyl moiety. The attack of 2 on the starting gly-
sugars are prepared in three steps, starting from fully pro- conolactone occurs selectively from the β-face leading to a
tected glycono-1,5-lactones. The procedure exploits a re- hemiacetal derivative, the spirocyclization of which is then
agent previously devised in our laboratory, the 3-C-lithiated
5,6-dihydro-1,4-dithiin-2-yl[(4-methoxybenzyl)oxy]methane
(2), that acts as an allylic alcohol anion equivalent leading to
three carbon elongations by introduction of a fully protected
accomplished by reaction with BF3·Et2O. The fully protected
unsaturated spiroacetals can be selectively desulfurized for
any further elaboration of the free double bond.
Introduction
Results and Discussion
Our procedure exploits a reagent previously devised in
our laboratory,[9] the 3-C-lithiated 5,6-dihydro-1,4-dithiin-
2-yl[(4-methoxybenzyl)oxy]methane (2), that has been
shown to act as an allylic alcohol anion equivalent, leading
to three-carbon elongations of suitable electrophiles by in-
troduction of a fully protected hydroxypropenyl moiety.
Compound 2 is prepared in situ from its parent compound
1, which is quite stable and can be stored in the refrigerator
for months.
Semi-rigid dioxaspiroacetal units are widely found as
sub-structures in many naturally occurring compounds
from different sources, including insects, microbes, plants,
fungi, and marine organisms.[1,2] The spiroacetal ring sys-
tem is also an essential part of the complex structures of
biologically active substances like the antiparasitic agents
avermectin[3] and milbemycin,[4] or the polyether antibiotics
of the monensin[5] and okadaic acid families.[6] The natur-
ally occurring chiral spiroacetal sub-structures mostly in-
clude 1,7-dioxaspiro[5.5]undecane, 1,6-dioxaspiro[4.5]de-
cane, and 1,6-dioxaspiro[4.4]nonane structural categories.
The spiroacetal synthesis is commonly accomplished by
the acid-promoted spirocyclization of a suitable dihydroxy
ketone precursor, generally leading to the correct configura-
tion of the spiro carbon provided that it corresponds to
the thermodynamically most stable form.[7] Recently, a new,
elegant approach to the synthesis of unsaturated pyranose
spiroacetals from perbenzylated glycono-1,5-lactones was
reported.[8] It is based on the ring-closing metathesis reac-
tion (RCM), in the presence of Grubbs ruthenium catalyst,
of a terminal alkene-O-alkene arrangement created in three
steps at the anomeric centre of sugars.
Under our conditions, compound 2 was directly coupled
with the proper glycono-1,5-lactone to afford the corres-
ponding hemiacetal, as shown in Scheme 1. The formation
of the sole thermodynamically more stable[10] hemiacetals
1
6؊8 was confirmed by H NMR spectroscopy.[11]
A crucial step in the overall conversion of glycono-1,5-
lactones into the corresponding spiroacetals is the induc-
tion of an electrophilic centre at the allylic methylene posi-
tion of the 1,4-dithiinyl moiety to be attacked by the free
hemiacetal hydroxyl group. This was achieved by BF3·Et2O
catalysis, under conditions that did not affect the hemiace-
tal hydroxyl group. In this way we could prepare the three
unsaturated spiroacetals 9؊11 with the double bond still
protected by the dimethylene-disulfur bridge in good yields.
The usual conditions to remove the MPM protection[12,13]
In this context we report here an alternative approach to
the synthesis of perbenzylated 1,6-dioxaspiro[4.5]dec-3-ene
derivatives of sugars that is accomplished in three steps
from the same glycono-1,5-lactone precursors.
[a]
`
Dipartimento di Chimica Organica e Biochimica, Universita di
Napoli Federico II
Via Cynthia, 4 80126 Napoli, Italy
Fax: (internat.) ϩ39-081/674-102
E-mail: ctsgroup@unina.it
534
WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0203Ϫ0534 $ 17.50ϩ.50/0 Eur. J. Org. Chem. 2002, 534Ϫ536

Fully Protected 1,6-Dioxaspiro[4.5]dec-3-ene Derivatives of Sugars
FULL PAPER
H, SCH2CHHS), 2.85Ϫ2.92 (m, 1 H, SCH2CHHS), 3.38 (s, 3 H,
OMe), 3.67 (d, J ϭ 10.0 Hz, 1 H, 7-Ha), 3.72 (d, J ϭ 11.3 Hz, 1
H, Bzli-Ha), 3.96 (dd, J ϭ 2.1, 8.9 Hz, 1 H, 7-Hb), 4.02 (t, J ϭ
9.1 Hz, 1 H, 5-H), 4.22 (d, J ϭ 2.6 Hz, 1 H, 3-H), 4.28 (m, 1 H, 6-
H), 4.32 (m, 3 H, CH2Cϭ and 4-H), 4.54 (d, J ϭ 12.2 Hz, 1 H,
Bzlii-Ha), 4.71 (d, J ϭ 10.5 Hz, 1 H, Bzliv-Ha), 4.76 (d, J ϭ 12.2 Hz,
1 H, Bzlii-Hb), 4.80 (d, J ϭ 11.3 Hz, 1 H, Bzliii-Ha), 4.98 (m, 4 H,
CH2C6H4OMe, Bzliv-Hb and Bzliii-Hb), 5.47 (d, J ϭ 11.3 Hz, 1 H,
Bzli-Hb), 5.58 (br. s, 1 H, OH), 6.79 (d, Jortho ϭ 8.7 Hz, 2 H, Harom),
7.45Ϫ7.17 (m, 22 H, Harom). 13C NMR: δ ϭ 26.5, 30.4, 54.8, 59.9,
68.2, 71.6, 72.1, 73.0, 74.5, 75.1, 75.4, 77.7, 82.1, 82.9, 99.7, 113.8.
The following hemiacetals were also obtained under the same con-
ditions.
(2R,3S,4S,5R,6R)-3,4,5-Tri(benzyloxy)-6-[(benzyloxy)methyl)]-
5,6-dihydro-2-{3-[(4-methoxybenzyloxy)methyl]-1,4-dithiin-2-yl}-
tetrahydro-2H-2-pyranol (7) from
D-Mannonolactone (4): Yield:
87%. Oil. [α]2D5 ϭ Ϫ19.2 (c ϭ 0.2). C47H50O8S2 (807.0): calcd. C
69.95, H 6.24; found C 69.50, H 6.30. 1H NMR: δ ϭ 2.42Ϫ2.58
(m, 3 H, SCH2CHHS), 2.71Ϫ2.85 (m, 1 H, SCH2CHHS), 3.36 (s,
3 H, OMe), 3.75Ϫ3.83 (m, J ϭ 3.6 Hz, 2 H, H-7), 4.19 (d, J ϭ
11.3 Hz, 1 H, Bzli-Ha), 4.21Ϫ4.34 (m, 1 H, H-6), 4.38Ϫ4.55 (m, 6
H, CH2CϭC and H-3 and H-4 and H-5, and Bzlii-Ha), 4.57Ϫ4.64
(m, 4 H, Bzlii-Hb, Bzliii-Ha and CH2C6H4OMe), 4.97 (d, J ϭ
11.1 Hz, 1 H, Bzliv-Ha), 5.03 (d, J ϭ 11.4 Hz, 1 H, Bzliii-Hb), 5.24
(d, J ϭ 11.1 Hz, 1 H, Bzliv-Hb), 5.41 (d, J ϭ 11.3 Hz, 1 H, Bzli-
Hb), 6.78 (d, Jortho ϭ 8.7 Hz, 2 H, Harom), 7.18Ϫ7.59 (m, 22 H,
Scheme 1
Ϫ treatment with either NaBH3CN or DDQ Ϫ led invari-
ably to the free primary alcohol that could be isolated as
such.[14]
Desulfurization with Raney-Ni in glacial acetic acid[15]
eventually afforded the 1,6-dioxaspiro[4.5]dec-3-ene derivat-
ives 12؊14 of the starting glycono-1,5-lactones 3؊5, re- Harom). 13C NMR: δ ϭ 27.7, 31.4, 55.0, 69.6, 69.9, 71.7, 72.6, 73.8,
74.6, 74.9, 76.4, 77.6, 79.5, 81.6, 100.6, 113.6.
spectively.
The whole procedure is very simple, and is characterized
by clean and high yielding reactions. The double bond in
the final sulfur-free unsaturated spiroacetals can be easily
saturated by catalytic hydrogenation, and hydroxylated un-
der stereocontrolled conditions as well, to synthesise other
more complex dioxaspiroacetal-based compounds.
(2R,3R,4S,5S,6R)-3,4,5-Tri(benzyloxy)-6-[(benzyloxy)methyl]-
5,6-dihydro-2-{3-[(4-methoxybenzyloxy)methyl]-1,4-dithiin-2-yl}-
tetrahydro-2H-2-pyranol (8) from
D-Galactonolactone (5): (89%),
oil, [α]2D5 ϭ ϩ16.4 (c ϭ 0.7). C47H50O8S2 (807.0): calcd. C 69.95, H
6.24; found C 69.78, H 6.17. 1H NMR: δ ϭ 2.44Ϫ2.52 (m, 2 H,
SCH2CH2S), 2.58Ϫ2.64 (m, 1 H, SCH2CHHS), 2.71Ϫ2.81 (m, 1
H, SCH2CHHS), 3.38 (s, 3 H, OMe), 3.70 (dd, J ϭ 5.3, 8.9 Hz, 1
H, 7-Ha), 3.95 (m, 2 H, 7-Hb and Bzli-Ha), 4.05 (dd, J ϭ 2.7,
9.7 Hz, 1 H, 4-H), 4.08Ϫ4.13 (m, 1 H, 5-H), 4.26Ϫ4.42 (m, 4 H,
3-H, Bzlii-Ha, CH2Cϭ), 4.46Ϫ4.54 (m, 1 H, 6-H), 4.55 (d, J ϭ
11.8 Hz, 1 H, CHHC6H4OMe), 4.64 (d, J ϭ 11.8 Hz, 1 H,
CHHC6H4OMe), 4.78 (t, J ϭ 11.3 Hz, 2 H, Bzliii-H), 4.87 (d, J ϭ
10.7 Hz, 1 H, Bzliv-Ha), 4.98 (m, 2 H, OH and Bzlii-Hb), 5.15 (d,
J ϭ 10.7 Hz, 1 H, Bzliv-Hb), 5.41 (d, J ϭ 11.3 Hz, 1 H, Bzli-Hb),
6.81(d, Jortho ϭ 8.6 Hz, 2 H, Harom), 7.13Ϫ7.50 (m, 22 H, Harom).
13C NMR: δ ϭ 27.7, 29.8, 55.2, 64.9, 68.1, 70.3, 70.8, 71.5, 72.4,
72.7, 73.4, 74.7, 75.7, 80.5, 96.5, 114.1.
Experimental Section
1
General: H (in C6D6) and 13C (in CDCl3) NMR spectra: Bruker
DRX-400 spectrometer, chemical shifts in ppm (δ), TMS internal
standard. Optical rotations (in CHCl3): Jasco P-1010 (1.0 dm cell).
Combustion analyses: PerkinϪElmer Series II 2400, CHNS ana-
lyzer. TLC analyses: silica gel Merck 60 F254 plates (0.2 mm layer
thickness). Column chromatography: Merck Kieselgel 60 (70Ϫ230
mesh). Dry solvents were distilled immediately before use.
Hemiacetal Formation. (2R,3R,4S,5R,6R)-3,4,5-Tri(benzyloxy)-6-
[(benz-yloxy)methyl]-5,6-dihydro-2-{3-[(4-methoxybenzyloxy)- Spirocyclization of Hemiacetal 6 to Compound 9. Typical Procedure:
methyl]-1,4-dithiin2-yl}tetrahydro-2H-2-pyranol (6). Typical Proced- A solution (3% v/v in CH2Cl2) of BF3·Et2O (0.2 mL) was added
ure: 1.6  BuLi in hexane (0.9 mL, 1.4 mmol) was added dropwise
carefully to a magnetically stirred solution of hemiacetal 6 (0.81 g,
over 10 min to a stirred solution of 5,6-dihydro-1,4-dithiin-2-yl-[(4-
1.0 mmol) in CH2Cl2 (14 mL) at room temperature. After 1 h, the
methoxybenzyl)oxy]methane (1) (0.32 g, 1.2 mmol) in anhydrous reaction mixture was quenched with Et3N (0.03 mL, 0.2 mmol) and
THF (5 mL), at Ϫ78 °C under an N2 atmosphere. After 40 min, -
gluconolactone (3) (0.54 g, 1.0 mmol) dissolved in the same solvent
then washed with water. The organic layer was dried (Na2SO4) and
the solvents evaporated under reduced pressure to afford a crude
(2 mL) was added dropwise with a cannula. The reaction mixture residue, the chromatographic separation of which on a silica gel
was kept for 3 h at Ϫ78° C, then quenched with 10% aq NH4Cl
(5 mL), and extracted with EtOAc (3 ϫ 15 mL). The combined
organic layers were dried (Na2SO4) and the solvents evaporated (668.7): calcd. C 70.03, H 6.03; found C 70.30, H 6.07. H NMR:
column (light petroleum ether/EtOAc: 8:2) afforded the pure spi-
roacetal 9 (0.58 g, 87%), oil, [α]2D5 ϭ ϩ21.1 (c ϭ 0.6). C39H40O6S2
1
under reduced pressure. Chromatography on silica gel (light petro-
δ ϭ 2.22Ϫ2.51 (m, 4 H, SCH2CH2S), 3.60 (dd, J ϭ 1.7 and
leum ether/EtOAc 7:3) of the crude residue finally afforded the pure 11.2 Hz, 1 H, 11-Ha), 3.79 (dd, J ϭ 3.4 and 11.2 Hz, 1 H, 11-Hb),
hemiacetal 6 (0.73 g, 90%) as an oil. [α]2D5 ϭ ϩ84.4 (c ϭ 0.6). 3.90 (t, J ϭ 9.2 Hz, 1 H, 8-H), 3.94 (d, J ϭ 10.3 Hz, 1 H, Bzli-Ha),
C47H50O8S2 (807.0): calcd. C 69.95, H 6.24; found C 69.15, H 6.15.
4.15Ϫ4.25 (m, 2 H, 7-H and 9-H), 4.32 (d, J ϭ 10.3 Hz, 1 H, Bzli-
1H NMR: δ ϭ 2.38Ϫ2.50 (m, 2 H, SCH2CH2S), 2.54Ϫ2.60 (m, 1 Hb), 4.40 (d, J ϭ 12.2 Hz, 1 H, Bzlii-Ha), 4.57 (d, J ϭ 12.2 Hz, 1
Eur. J. Org. Chem. 2002, 534Ϫ536
535

R. Caputo, A. Guaragna, G. Palumbo, S. Pedatella, F. Solla
FULL PAPER
H, Bzlii-Hb), 4.63 (m, 3 H, 10-H and Bzliii-H), 4.81Ϫ5.01 (m, 4 H,
H, 11-Hb), 4.25Ϫ4.42 (m, 2 H, 7-H and 9-H), 4.30 (d, J ϭ 12.2 Hz,
Bzliv-H and 2-H), 6.98Ϫ7.37 (m, 20 H, Harom). 13C NMR: δ ϭ 2 H, Bzli-Ha), 4.52Ϫ4.81 (m, 6 H, 2-H, 8-H, Bzli-Hb, Bzlii-Ha and
25.3, 26.0, 68.5, 73.2, 74.7, 75.1, 75.4, 77.7, 80.9, 83.3, 95.9, 113.2, Bzliii-Ha), 4.88Ϫ5.05 (m, 3 H, Bzlii-Hb, Bzliii-Hb and Bzliv-Ha), 5.18
117.9, 124.4.
(d, J ϭ 10.9 Hz, 1 H, Bzliv-Ha), 5.72 (dt, J ϭ 6.14 and 2.39 Hz, 1
H, 3-H), 5.89 (d, J ϭ 6.14 Hz, 1 H, 4-H) 7.11Ϫ7.36 (m, 20 H,
Harom). 13C NMR: δ ϭ 68.5, 70.2, 73.85, 73.6, 73.7, 74.5, 74.9,
80.1, 82.1, 82.4, 103.9, 111.4. 113.4.
The following spiroacetals were also obtained under the same con-
ditions.
Compound 10, from Hemiacetal 7: Yield: 85%, oil. [α]2D5 ϭ ϩ22.3
(c ϭ 0.7). C39H40O6S2 (668.7): calcd. C 70.03, H 6.03; found C
70.16, H 5.98. 1H NMR: δ ϭ 2.23Ϫ2.57 (m, 4 H, SCH2CH2S),
3.82 (dd, J ϭ 1.8 and 11.6 Hz, 1 H, 11-Ha), 3.93 (d, J ϭ 2.39 Hz,
1 H, 10-H), 4.08 (dd, J ϭ 3.8 and 11.6 Hz, 1 H, 11-Hb), 4.25Ϫ4.31
(m, 1 H, 7-H), 4.38 (dd, J ϭ 2.4, 9.3 Hz, 1 H, 9-H), 4.47 (d, J ϭ
12.2 Hz, 1 H, Bzli-Ha), 4.58 (t, J ϭ 9.3 Hz, 1 H, 8-H), 4.62 (d, J ϭ
11.9 Hz, 1 H, Bzlii-Ha), 4.64Ϫ4.74 (m, 3 H, 2-H and Bzli-Hb), 4.77
(d, J ϭ 11.4 Hz, 1 H, Bzliii-Ha), 4.92Ϫ5.06 (m, 3 H, Bzlii-Hb, Bzliii-
Hb and Bzliv-Ha), 5.18 (d, J ϭ 11.3 Hz, 1 H, Bzliv-Hb), 7.14Ϫ7.36
(m, 20 H, Harom). 13C NMR: δ ϭ 25.7, 25.9, 68.7, 72.2, 73.1, 73.8,
74.2, 74.6, 74.8, 75.9, 77.1, 78.6, 81.3, 113.4, 123.1.
(5R,7R,8S,9S,10R)-8,9,10-Tri(benzyloxy)-7-[(benzyloxy)methyl]-
1,6-dioxaspiro[4.5]dec-3-ene (14) from Spiroacetal 11: Yield: 69%,
oil. [α]2D5 ϭ ϩ25 (c ϭ 0.2). C37H38O6 (578.3): calcd. C 76.79, H
6.62; found C 76.87, H 6.20. 1H NMR: δ ϭ 3.77 (dd, J ϭ 8.8,
5.4 Hz, 1 H, 11-Ha), 3.95 (t, J ϭ 8.8 Hz, 1 H, 11-Hb), 4.10Ϫ4.15
(m, 1 H, 8-H), 4.18Ϫ4.51 (m, 3 H, 9-H and Bzli-H), 4.55Ϫ4.60 (m,
4 H, 2-H, 7-H and Bzlii-Ha), 4.65Ϫ4.90 (m, 5 H, 10-H, Bzlii-Hb,
Bzliii-H and Bzliv-Ha), 5.02 (d, J ϭ 11.2 Hz, 1 H, Bzliv-Hb), 5.55
(dt, J ϭ 5.9, 2.5 Hz, 1 H, 3-H), 5.62 (d, J ϭ 5.9 Hz, 1 H, 4-H),
7.16Ϫ7.39 (m, 20 H, Harom). 13C NMR: δ ϭ 69.8, 70.8, 71.5, 72.9,
73.3, 74.9, 75.4, 77.1, 77.2, 81.6, 96.1, 109.6, 110.5.
Acknowledgments
Compound 11, from Hemiacetal 8: Yield: 82%, oil. [α]2D5 ϭ ϩ4.7
(c ϭ 0.3). C39H40O6S2 (668.7): calcd. C 70.03, H 6.03; found C
70.21, H 5.98. 1H NMR: δ ϭ 2.32Ϫ2.47 (m, 3 H, SCH2CHHS),
2.52Ϫ2.62 (m, 1 H, SCH2CHHS), 3.74 (dd, J ϭ 8.8, 5.4 Hz, 1 H,
11-Ha), 3.90 (t, J ϭ 8.8 Hz, 1 H, 11-Hb), 4.10Ϫ4.16 (m, 1 H, 8-H),
4.22 (dd, J ϭ 2.8, 9.9 Hz, 1 H, 9-H), 4.28 (d, J ϭ 11.9 Hz, 1 H,
Bzli-Ha), 4.34 (d, J ϭ 11.9 Hz, 1 H, Bzli-Hb), 4.47Ϫ4.52 (m, 1 H,
7-H), 4.55 (d, J ϭ 11.8 Hz, 1 H, Bzlii-Ha), 4.61 (d, J ϭ 9.9 Hz, 1 H,
Bzlii-Hb), 4.68 (d, J ϭ 9.9 Hz, 1 H, 2-H), 4.72Ϫ4.83 (m, 3 H, 2-H
and Bzliv-Ha), 4.92 (d, J ϭ 11.1 Hz, 1 H, Bzliii-Ha), 5.05 (d, J ϭ
11.1 Hz, 1 H, Bzliii-Hb), 5.17 (d, J ϭ 11.8 Hz, 1 H, Bzliv-Hb),
7.11Ϫ7.50 (m, 20 H, Harom). 13C NMR: δ ϭ 25.6, 26.2, 68.4, 71.6,
72.8, 73.4, 74.3, 74.5, 75.4, 76.6, 77.9, 80.9, 96.1, 113.4, 118.5, 124.2.
1H and 13C NMR spectra, and Amber3 calculations, were per-
formed at the Centro Interdipartimentale di Metodologie Chimico-
`
Fisiche, Universita di Napoli Federico II.
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Desulfurization. Formation of (5R,7R,8R,9S,10R)-8,9,10-Tri(ben-
zyloxy)-7-[(benzyloxy) methyl]-1,6-dioxaspiro[4.5]dec-3-ene (12).
Typical Procedure: A solution of spiroacetal 9 (0.1 g, 0.15 mmol)
in glacial acetic acid (3 mL) was added in one portion to a stirred
suspension of Raney-Ni (W2) (1.5 g, wet) in the same solvent
(2 mL) at room temperature. The suspension was stirred for 35 min
(TLC monitoring). The solid was then filtered off and washed with
EtOAc. The filtrate was neutralized with saturated aq Na2CO3 and
extracted with EtOAc (3 ϫ 15 mL). The combined organic layers
were washed with water until neutral, dried (Na2SO4), and the solv-
ents evaporated under reduced pressure to afford a crude residue.
Chromatography of the latter on a silica gel column (light petro-
leum ether/EtOAc: 8:2) gave the pure sulfur-free spiroacetal 12
(0.07 g, 77%) as an oil. [α]2D5 ϭ ϩ30.1 (c ϭ 0.2). C37H38O6 (578.3):
calcd. C 76.79, H 6.62; found C 76.85, H 6.48. 1H NMR: δ ϭ 3.62
(dd, J ϭ 1.9 and 10.8 Hz, 1 H, 11-Ha), 3.80 (dd, J ϭ 3.2 and
10.8 Hz, 1 H, 11-Hb), 3.91Ϫ4.05 (m, 2 H, 8-H and Bzli-Ha),
4.17Ϫ4.53 (m, 8 H, 2-H, 7-H, 9-H, 10-H, Bzlii-H and Bzli-Hb),
4.60Ϫ5.01 (m, 4 H, Bzliii-H and Bzliv-H), 5.43 (dt, J ϭ 6.1, 2.4 Hz,
1 H, 3-H), 5.62 (dt, J ϭ 1.2, 6.1 Hz, 1 H, 4-H), 7.12Ϫ7.39 (m, 20
H, Harom). 13C NMR: δ ϭ 68.7, 72.4, 73.4, 74.8, 75.7, 76.3, 76.7,
78.5, 81.4, 83.7, 96.1, 109.5, 112.1.
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kJ molϪ1 (compound 6), Ϫ14.6 kJ molϪ1 (compound 7), and
Ϫ21.1 kJ molϪ1 (compound 8).
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[14]
A. Srikrishna, R. Viswajanani, J. A. Sattigeri, D. Vijaykumar,
J. Org. Chem. 1995, 60, 5961Ϫ5962.
K. Horita, T. Yoshioka, T. Tanaka, Y. Oikawa, O. Yonemitsu,
Tetrahedron 1986, 42, 3021Ϫ3028.
Most of the experiments aimed to devise proper cyclization
conditions were performed with compound 6 as a model, and
the relevant 1H NMR peaks of the corresponding free primary
alcohol were: δ ϭ 2.30Ϫ2.82 (m, 4 H, SCH2CH2S), 3.51 (d,
J ϭ 11.0 Hz, 1 H, 7-Ha), 3.62Ϫ3.70 (m, J ϭ 11.3 Hz, 2 H, 6-
H and 7-Hb), 3.72Ϫ3.82 (m, 2 H, 3-H and 5-H), 4.18 (t, J ϭ
9.0 Hz, 1 H, 4-H), 4.49 (d, J ϭ 12.0 Hz, 1 H, CHaOH),
4.55Ϫ4.70 (m, 4 H, CHbOH and Bzl-H), 4.81 (d, J ϭ 11.0 Hz,
1 H, Bzli-Ha), 4.84 (d, J ϭ 11.0 Hz, 1 H, Bzli-Hb), 4.90 (d, J ϭ
12.2 Hz, 1 H, Bzlii-Ha), 4.97 (d, J ϭ 12.2 Hz, 1 H, Bzlii-Hb),
4.99 (d, J ϭ 11.0 Hz, 1 H, Bzl-H), 7.03Ϫ7.49 (m, 20 H, Harom).
R. Caputo, G. Palumbo, S. Pedatella, Tetrahedron 1994, 50,
7265Ϫ7268.
The following desulfurized spiroacetals were also obtained under
the same conditions.
(5R,7R,8R,9S,10S)-8,9,10-Tri(benzyloxy)-7-[(benzyloxy)methyl]-
1,6-dioxaspiro[4.5]dec-3-ene (13) from Spiroacetal 10: Yield: 70%,
oil. [α]2D5 ϭ ϩ10.2 (c ϭ 0.04). C37H38O6 (578): calcd. C 76.79, H
[15]
1
6.62; found C 76.31, H 6.12. H NMR: δ ϭ 3.89 (d, J ϭ 11.6 Hz,
Received July 20, 2001
1 H, 11-Ha), 3.98 (br. s, 1 H, 10-H), 4.08 (dd, J ϭ 4.0, 11.6 Hz, 1
[O01360]
536
Eur. J. Org. Chem. 2002, 534Ϫ536