Back to the sugars: A new enantio and diastereocontrolled route to hexoses from furfural

Article abstract of DOI:10.1055/s-1999-3382

An integrated enantio and diastereocontrolled route to both enantiomers of the eight possible hexoses has been explored starting from furfural, by employing the Sharpless asymmetric dihydroxylation as a key step. At the present, a route to six of the eight possible hexoses has been established. The present synthesis may be taken as a reversion of the sugar-originated furfural to the sugars via a levoglucosenone, a pyrolysate of cellulose, type intermediate.

Full text of DOI:10.1055/s-1999-3382

FEATURE ARTICLE
341
Back to the Sugars: A New Enantio and Diastereocontrolled Route to Hexoses
from Furfural
Miwako Takeuchi, Takahiko Taniguchi, Kunio Ogasawara*
Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Fax +81(22)2176845; E-mail: konol@mail.cc.tohoku.ac.jp
Received 1 October 1998
Dedicated to the memory of Professor George BŸchi
be a versatile chiral building block and was actually used
Abstract: An integrated enantio and diastereocontrolled route to
for the enantiocontrolled production of several natural
both enantiomers of the eight possible hexoses has been explored
products.5 However, its inefficient production and limited
starting from furfural, by employing the Sharpless asymmetric
dihydroxylation as a key step. At the present, a route to six of the
enantiomeric availability6 restricted to the cellulose con-
eight possible hexoses has been established. The present synthesis figuration prevented its use as a versatile chiral building
may be taken as a reversion of the sugar-originated furfural to the
sugars via a levoglucosenone, a pyrolysate of cellulose, type inter-
mediate.
block. We, therefore, examined the asymmetric synthesis
of levoglucosenone 8 and have established its preparation
in both enantiomeric forms without using carbohydrate
Key words: asymmetric dihydroxylation, furfural, hexoses, oxida-
tive ring expansion, enantiocontrolled synthesis
precursors. In the synthesis, we employed the Sharpless
asymmetric dihydroxylation reaction7 to introduce the
chirality of the target levoglucosenone 8. Thus, 2-vinylfu-
ran (2) generated from furfural (1), furnished the (+)-(R)-
glycol 3 with AD-mix-a and the (Ð)-(S)-glycol 3 with
AD-mix-b, as expected by the empirical rule, in 90 and
93% ee. Recrystallization, after converting the products
into the corresponding dibenzoates, afforded the optically
pure products (>99% ee). Exposure of the glycol 3 with 3-
chloroperbenzoic acid (MCPBA) induced the oxidative
furan-ring expansion8,9 to give the 3-pyrone derivative 4
as a mixture at the hemiacetal center. Intramolecular acet-
alization of the mixture was next carried out in the pres-
ence of an acid catalyst to afford the bicyclic acetal 5
having a dioxabicyclo[3.2.1]octane framework.10 Overall
yields of (+)-5 from (+)-3 and (Ð)-5 from (Ð)-3 were 42
and 44%, respectively. Functionally, the bicyclic enone 5
is taken to be the same as levoglucosenone 8 which pos-
sesses the isomeric enone functionality on the same di-
oxabicyclo[3.2.1]octane framework. In order to obtain
levoglucosenone 8, the enone functionality of 5 was
isomerized by employing the Wharton rearrangement.11
Thus, 5 was treated with alkaline hydrogen peroxide to
give the single exo-epoxide 6 in which the reaction oc-
curred exclusively from the less hindered convex face.
Thus, (+)-5 afforded (Ð)-epoxide 6 and (Ð)-5 afforded (+)-
epoxide 6 both in 71% yields. Treatment of the epoxide 5
with hydrazine hydrate gave the single allylic alcohol 7
which yielded levoglucosenone 8 on oxidation with man-
ganese(IV) oxide. Overall yields of (Ð)-levoglucosenone
(8) via (Ð)-allyl alcohol 7 and (+)-ent-levoglucosenone (8)
via (+)-allyl alcohol 7 were 50% (Scheme 1).
The hexoses are stereoisomers having a concatenation of
four contiguous hydroxy-bearing carbogenic centers.
Their enantiocontrolled synthesis, therefore, requires a
procedure leading to eight pairs of stereoisomers in an
enantio and diastereocontrolled manner. So far, the proce-
dure devised by the groups of Masamune and Sharpless1
employing the KatsukiÐSharpless asymmetric ep-
oxidation2 coped only with precise installation of four
contiguous hydroxy functionalities to give rise to all hex-
oses. The MasamuneÐSharpless synthesis is based on the
reiterative application of the asymmetric epoxidation and
stereoselective two-carbon extension starting from a
glyoxyaldehyde unit. This procedure allowed the installa-
tion of the four hydroxy-bearing centers through two cy-
cles comprising stereoselective construction of the allylic
alcohol functionality and its enantiocontrolled epoxida-
tion using an appropriate chiral tartrate followed by ste-
reo- and regioselective opening of the oxirane ring
generated. Although the procedure provides a concise and
flexible way to the hexoses, we felt that it still left us the
challenge to devise an alternative procedure that does not
require reiteration of the two-carbon elongation and the
asymmetric epoxidation. We wish to report here a new
strategy capable of producing all the stereoisomers of the
hexoses from a single starting material employing a single
asymmetric chiral induction step.
As the basis of the present study, we established an enan-
tiocontrolled synthesis of levoglucosenone3 8 of which
only the (Ð)-enantiomer was obtained in a low yield by
acid-catalyzed thermolysis4 of cellulose, a hexose poly-
mer. Owing to its enone functionality and masked formyl
and 1,2-glycol functionalities confined in the biased bicy-
clic framework, levoglucosenone 8 has been expected to
In a sense, the above synthesis of levoglucosenone 8 may
be taken to be a reversion of the synthesis of furfural (1)
as it is obtained from naturally occurring substances con-
taining pentose fragments such as corncobs12 and straw
though levoglucosenone 8 is not pentose but hexose in or-
igin.4 We, therefore, envisaged that the present route
could be further traced back to the pentose stage as well as
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342
M. Takeuchi et al.
FEATURE ARTICLE
Scheme 1
Biographical Sketches
Kunio Ogasawara was Professor George BŸchi at 1994 at the Department of
born in 1938 in Kagoshima, Massachusetts Institute of Organic Synthesis, Pharma-
Japan. He studied at the Technology from 1968 to ceutical Institute, Tohoku
Pharmaceutical Institute at 1971, he returned to the University. His research in-
Tohoku University in Sen- Pharmaceutical
Institute, terests are in the field of
dai where he received his Tohoku University where synthetic organic chemistry
PhD degree in 1968 under he worked with Professor in particular enantiocon-
the direction of Professor Seiichi Takano for 22 years trolled synthesis of natural
Tetsuji Kametani. After as Associate Professor. He products.
postdoctoral studies with has been Professor since
Miwako Takeuchi was Tohoku University in Sen- of
Professor
Kunio
born in 1976 in Ibaraki, Ja- dai. She is currently work- Ogasawara at the Pharma-
pan. She received her bach- ing towards her masterÕs ceutical Institute, Tohoku
elorÕs degree in 1998 from degree under the direction University in Sendai.
Takahiko Taniguchi was mada, and PhD degree in fessor. His current research
born in 1967 in Shiga, Ja- 1994 from Tohoku Univer- interests is the development
pan. He received his bache- sity under the direction of of versatile chiral building
lorÕs and masterÕs degree Professor Keiichiro Fuku- blocks and their utilization
from Tokyo College of moto. In 1994, he joined in natural product synthesis.
Pharmacy under the direc- Professor
OgasawaraÕs
tion of Professor Yasuji Ya- group as an Assistant Pro-
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FEATURE ARTICLE
Back to the Sugars
343
to the hexose stage via a common levoglucosenone-type lyl alcohol13 9 (R = H). On reaction using AD-mix-a and
intermediate. Since the synthesis of the pentoses is less -b, 9 afforded the chiral glycols 10 both in 90% yield
challenging, we decided to examine the synthesis of all with >99% ee, respectively. The observed remarkable
stereoisomers of the hexoses starting from furfural (1) enhancement of asymmetric induction of 9, which pos-
based on the levoglucosenone synthesis above.
sesses one extra carbon functionality on the monosub-
stituted alkene 2, is worthy of note even though it was
anticipated to some extent. Oxidative furan ring expan-
sion of 10 proceeded with MCPBA9 to give rise to the 3-
pyrone 12 which afforded the key intermediate 11, on
acid treatment, having a dioxabicyclo[3.2.1]octane
structure (Scheme 3).
The essential features of the present synthesis are outlined
in a general way in Scheme 2. The strategy is based on the
utilization of the levoglucosenone-type intermediate 11
having an extra hydroxymethyl functionality to control
the regioselective cleavage of the bicyclic system and to
discriminate the two terminal functionalities of the sub-
strate (marked as • and ∆). With respect to the construc- Having obtained the key starting material, we first exam-
tion of the four contiguous hydroxy-bearing centers, as ined its conversion into the hexoses by stereoselective
the key intermediate 11 possesses a fixed oxygen func- modification of the enone functionality and by regioselec-
tionality fated to be one of the four contiguous hydroxy tive cleavage of the dioxolane moiety. Reduction of 11
functionalities, it was planned to install the three remain- with sodium borohydrideÐCe(III) chloride14 proceeded
ing by modification of the enone functionality. The most stereoselectively to give the single allyl alcohol 13 excel-
salient feature of the strategy in the present synthesis is the lently. After benzylation, the resulting benzyl ether 14
use of the key intermediate 11 in two ways, namely the ac- was dihydroxylated15 to give the single diol 15 which was
etal carbon and the C2 of the glycol carbons are placed at again benzylated to give the tribenzyl ether 16 having four
either the C1 formyl functionality or the C6 hydroxymeth- contiguous oxygen-bearing centers. Both the reduction
yl functionality of the target hexoses so as to produce the and the dihydroxylation occurred stereoselectively from
isomeric and/or the enantiomeric hexoses from the same the convex face of the molecule, which was confirmed by
precursor (Scheme 2).
conversion into two hexoses, L-gulose 23 and D-glucose
27, as described below (Schemes 3 and 4).
To obtain L-gulose (23), the tribenzyl ether 16 was desily-
lated to give the primary alcohol 17 which was further
transformed into the iodide 19 via the mesylate 18. On
treatment with zinc in acetic acid, 19 furnished the six-
membered hemiacetal 20 as an epimeric mixture by re-
ductive cleavage of the dioxolane ring. Treatment of 20
with benzyl alcohol in the presence of an acid catalyst
gave a mixture of the benzyl acetal 21 whose vinyl func-
tionality was sequentially cleaved and reduced16 to give
the primary alcohol 22. Finally, 22 was debenzylated un-
der catalytic hydrogenolysis conditions to give L-gulose
(23) (Scheme 3).
Scheme 2
On the other hand, the hemiacetal mixture 20 was reduced
with lithium aluminum hydride to give the diol 24 which
was benzylated to give the pentabenzyl ether 25. The
vinyl functionality of 25 was then cleaved by sequential
dihydroxylation and periodate oxidation16 to give the al-
The actual synthesis commenced with the asymmetric di-
hydroxylation of the allyl ether 9 (R=TBS) which was
readily prepared in three steps from furfural (1) via the al-
Scheme 3
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344
M. Takeuchi et al.
FEATURE ARTICLE
dehyde 26 which was subjected to catalytic hydrogenol- was treated with boron trifluorideÐdiethyl ether complex
ysis to remove the benzyl groups to give D-glucose (27) to cleave the epoxide bond stereoselectively by the neigh-
(Scheme 4).
boring group participation of the benzoate functionality.18
The reaction proceeded with stereoselective cleavage of
the epoxide bond, but the silyl protecting group was re-
moved under the conditions to give a mixture of the triols
37. Since discrimination of the primary alcohol from the
secondary alcohols in 37 was found to be difficult, the ep-
oxybenzoate 39 bearing a different protecting group19 was
prepared from the allyl alcohol 9 (R = H) via the enone 11
(P = 2-naphthylCH2), the epoxide 34 (P = 2-naphthylCH2)
and the alcohol 38 (P = 2-naphthylCH2) by employing the
same procedure. Reaction of 39 with boron trifluorideÐdi-
ethyl ether complex18 afforded the single diol 40, without
affecting the protecting group, which gave the single triol
41 after removal of the benzoate group. After benzylation,
the tribenzyl ether 42 obtained was hydrogenated in etha-
nol on palladized charcoal (10%) to allow chemoselective
removal of the naphthylmethyl protecting group19 to give
the primary alcohol 43. As above, the dioxolane ring of 43
was cleaved in a three-step sequence via the mesylate 44
and the iodide 45 to give the hemiacetal 46 without diffi-
culty. This compound was then treated with benzyl alco-
hol in the presence of an acid catalyst to give the acetal
mixture 47 which was transformed into the primary alco-
hol 48 by sequential ozonolysis and borohydride reduc-
tion in the same flask as for 22. Hydrogenolysis of 48
furnished L-galactose 49 by removal of four benzyl
groups. Although we did not carry out the further conver-
sion, 46 may also serve as the precursor of the enantio-
meric D-galactose 49 on the same treatment as for the
synthesis of D-glucose 27 above (Scheme 6).
Scheme 4
Moreover, the hemiacetal mixture 20 was oxidized with
tetrapropylammonium perruthenate17 (TPAP) in the pres-
ence of N-methylmorphorine N-oxide (NMO) to give the
d-lactone 28 which, on treatment with 1,4-diazabicy-
clo[2.2.2]octane (DABCO), induced a-epimerization to
give the isomeric d-lactone 29 as a single product in sat-
isfactory yield after recrystallization. Reduction of 29
with diisobutylaluminum hydride (DIBAL) gave the
hemiacetal 30 as a mixture of epimers at the acetal center.
With the same treatment as for L-gulose 23, 30 could be
transformed into L-idose 33 via the tetrabenzyl ether 31
and the primary alcohol 32. Although we did not carry out
an alternative transformation, the same L-idose 33 may be
obtained from 30 on the same treatment as for the above
D-glucose 27 (Scheme 5).
Having established the route to the four hexoses, we next
examined the synthesis of the remaining four hexoses, al-
lose, altrose, talose and mannose starting from the oxo ep-
oxide 34. At present, since the Wharton reaction of 34, in
particular the substrate having a 2-naphthylmethyl protect-
ing group, was very capricious, we have just reached the
common intermediate 59 of L-altrose 60 and L-talose 61.
Thus, on treatment with hydrazine hydrate, the epoxide 34
(P = TBS) afforded the exo-allyl alcohol 50 which was
then converted into the enone 51 on oxidation. Reduction
of 51 with sodium borohydrideÐCe(III) chloride14 gave
the single endo-allyl alcohol 52 which was converted into
the benzyl ether 53. On the same treatment for the isomer-
ic 15, 53 furnished the exo-diol 54 diastereoselectively,
which was then benzylated to give the tribenzyl ether 55.
After removal of the silyl protecting group, the resulting
primary alcohol 56 was transformed into the iodide 58, via
the tosylate 57, which furnished the hemiacetal 59 expect-
ed to be served as the common precursor of L-altrose 60
and L-talose 61 on reductive treatment with zinc powder
in acetic acid (Scheme 7).
Scheme 5
Having established the conversion of the dioxabicyclooc-
tane framework into the hexose framework in two ways
by demonstrating the route to the three hexoses, we next
examined the stereocontrolled introduction of three con-
tiguous hydroxy groups on the enone system of the key in-
termediate 11 to obtain the remaining five hexoses.
Of two remaining hexoses, L-mannose 65 may be ob-
tained from the enone 51 having a 2-naphthylmethyl pro-
tecting group by employing the same procedure for the
isomeric enone 34 which gave rise to galactose 49 via the
intermediates 62, 63 and 64, while both enantiomeric al-
Treatment of 11 with alkaline hydrogen peroxide afforded
the single exo-epoxide 34 which gave the single endo-al-
cohol 35 on reduction with sodium borohydrideÐCe(III)
chloride.14 After benzoylation, the benzoate 36 obtained
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FEATURE ARTICLE
Back to the Sugars
345
Scheme 6
Scheme 7
with H2O (100 mL). The organic layer was separated, washed with
brine (50 mL) and dried (MgSO4). After evaporation of the solvent
under reduced pressure, the residue was chromatographed (silica
gel, 500 g, elution with EtOAcÐhexane 1:10 v/v) to remove a minor
amount of the Z-olefin (0.9 g, 2%) to give the pure (E)-acrylate
(42.1 g, 97%) as a pale yellow oil.
loses 67 may be obtained from the exo-allyl alcohol 50 via
the common intermediate 66 by application of the proce-
dure established for the closely related system20 (Scheme
8).
In conclusion, although the present study has not been
completed, the basis of our strategy for an integrated route
to both enantiomers of eight hexoses has been demonstrat-
ed. Further investigation for the completion of the present
procedure is currently in progress.
IR (film): n = 1710, 1640 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.48 (1 H, d, J = 1.6 Hz), 7.43 (1
H, d, J = 15.9 Hz), 6.60 (1 H, d, J = 3.4 Hz), 6.46 (1 H, dd, J = 3.4,
1.6 Hz), 6.32 (1 H, d, J = 15.9 Hz), 4.25 (2 H, q, J = 7.1 Hz), 1.32
(3 H, t, J = 7.1 Hz).
13C NMR (CDCl3, 75 MHz): d=166.9, 150.9, 144.6, 130.8, 115.8,
114.5, 112.1, 60.1, 14.0.
Melting points are uncorrected. IR spectra were recorded on a
1
JASCO-IR-700 spectrometer. H NMR spectra were recorded on
Gemini 2000 (300 MHz) or JEOL JMX-GX500 (500 MHz) spec-
trometers. Mass spectra were recorded on a JEOL JMS-DX303 in-
strument. Optical purities were determined on a Gilson Model-307
instrument equipped with a chiral column. Optical rotations were
measured with a JASCO-DIP-370 digital polarimeter.
HRMS calcd for C9H10O3 (M+) 166.0630, found 166.0610.
(E)-3-(2-Furfuryl)prop-2-en-1-ol (9:R = H)
To a stirred solution LiAlH4 (3.7 g, 96.4 mmol) in Et2O (400 mL)
was added the above acrylate (20 g, 120.4 mmol) in Et2O (100 mL)
at 0 ûC and the mixture was stirred at the same temperature for 1 h.
The excess hydride was quenched by addition of 28% NH4OH
(~10 mL) and after 2 h the mixture was filtered through a Celite
pad. The filtrate was evaporated under reduced pressure and the res-
idue was chromatographed (silica gel, 400 g, elution with EtOAcÐ
hexane, 1:2 v/v) to give 9 (R = H) (14.8 g, 97%) as a pale yellow oil.
(E)-3-(2-Furyl)prop-2-en-1-ol (9: R = H)
Ethyl (E)-3-(2-Furfuryl)acrylate
To a stirred suspension of NaH (60% in oil, 12.5 g, 0.31 mol) in
THF (450 mL) was added triethyl phosphonoacetate (72 mL,
0.36 mol) at 0¡C. After 30 min at the same temperature, furfural (1)
(25 g, 0.26 mol) in THF (50 mL) was added dropwise at the same
temperature. The mixture, after being kept stirring for 30 min at
room temperature, was diluted with Et2O (300 mL) and was treated
IR (film): n = 3328 cmÐ1.
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M. Takeuchi et al.
FEATURE ARTICLE
Scheme 8
1H NMR (CDCl3, 300 MHz): d = 7.35 (1 H, d, J = 1.5 Hz), 6.45 (1
H, dt, J = 15.9, 1.2 Hz), 6.37 (1 H, dd, J = 3.3, 1.5 Hz), 6.30 (1 H,
dt, J = 15.9, 5.7 Hz), 6.25 (1 H, d, J = 3.3 Hz), 4.30 (2 H, d, J =
5.7 Hz), 1.49 (1 H, br s).
naphthalene (25 g, 112.77 mmol) and Bu4NI (2.6 g, 70.48 mmol)
were added. After stirring for 8 h at r.t., MeOH (2 mL, 49.34 mmol)
and NaH (60% in oil, 1.97 g, 49.34 mmol) were added to the mix-
ture. The mixture was diluted with EtOAc (200 mL) and was
washed successively with H2O (40 mL) and brine (20 mL), and the
organic layer was dried (MgSO4). After evaporation of the solvent
under reduced pressure, the residue was chromatographed (silica
gel, 200 g, elution with EtOAcÐhexane, 1:200 then 1:30) to give the
ether 9 (R = 2-naphthylCH2) (17.69 g, 95%) as a pale yellow oil.
1H NMR (CDCl3, 300 MHz): d = 7.86Ð7.78 (4 H, m), 7.50Ð7.43 (3
H, m), 7.35 (1 H, br d, J = 1.7 Hz), 6.48 (1 H, d, J = 15.9 Hz), 6.36
(1 H, dd, J = 3.3, 1.7 Hz), 6.28 (1 H, dt, J = 15.9, 5.8 Hz), 6.24 (1
H, d, J = 3.3 Hz), 4.72 (2 H, s), 4.20 (2 H, dd, J = 5.8, 1.4 Hz).
HRMS calcd for C7H8O2 (M+) 124.0524, found 124.0482.
tert-Butyldimethylsilyl (E)-3-(2-Furyl)prop-2-enyl Ether
(9: R = TBS)
A mixture of 9 (R = H) (1.03 g, 8.34 mmol), Et3N (1.74 mL,
12.5 mmol), tert-butyldimethylchlorosilane (TBSCl) (1.51 g,
10.0 mmol) and 4-(N,N-dimethyl)pyridine (DMAP) (51 mg,
0.42 mmol) in CH2Cl2 (20 mL) was stirred at r.t. for 4 h. The mix-
ture was washed successively with H2O (5 mL) and brine (3 mL)
and dried (MgSO4). After removal of the solvent under reduced
pressure, the residue was chromatographed (silica gel, 25 g, elution
with EtOAcÐhexane, 1:100) to give the ether 9 (R = TBS) (1.95 g,
98%) as a yellow oil.
1H NMR (CDCl3, 300 MHz): d = 7.33 (1 H, d, J = 1.8 Hz), 6.43 (1
H, dt, J = 15.7, 1.8 Hz), 6.36 (1 H, dd, J = 3.2, 1.8 Hz), 6.23 (1 H,
dt, J = 15.7, 4.6 Hz), 6.21 (1 H, d, J = 3.2 Hz), 4.33 (2 H, dd, J =
4.6, 1.8 Hz), 0.93 (9 H, s), 0.10 (6 H, s).
HRMS calcd for C18H16O2 (M+) 264.1150, found 264.1132.
(Ð)-(1S,2R)-3-tert-Butyldimethylsiloxy-1-(2-furyl)propane-1,2-
diol (10: P = TBS)
To a stirred solution of 9 (R=TBS) (1.70 g, 7.13 mmol) in t-BuOHÐ
H2O (1:1 v/v, 60 mL), MeSO2NH2 (678 mg, 7.13 mmol), and AD-
mix-β (9.76 g) was added at 0 ûC and the mixture was stirred at the
same temperature for 95 h. The reaction was quenched by addition of
Na2SO3 (2.70 g, 21.4 mmol) and the mixture was extracted with
EtOAc (3 × 200 mL). The extract was washed successively with 10%
aq KOH (60 mL) and brine (30 mL), and dried (MgSO4). After evap-
oration of the solvent under reduced pressure, the residue was chro-
matographed (silica gel, 35 g, elution with EtOAcÐhexane, 1:5 v/v)
to give the glycol 10 (P = TBS) (1.83 g, 94%) as a pale yellow oil:
[α]D28 Ð1.70 (c =1.1, CHCl3). The optical purity was determined to be
99.6% ee by hplc using a chiral column (CHIRALCEL OD, elution
with i-PrOHÐhexane, 1:500 v/v) after conversion into the dibenzoate.
13C NMR (CDCl3, 75 MHz): d = 153.1, 141.8, 128.1, 117.8, 111.3,
107.3, 63.3, 25.9, 18.4, Ð5.3.
HRMS calcd for C13H22O2Si (M+) 238.1389, found 238.1381.
(E)-3-(2-Furyl)prop-2-enyl (2-Naphthylmethyl) Ether (9: R =
2-naphthylCH2)
To a stirred solution of 9 (R = H) (8.74 g, 70.48 mmol) in THF
(150 mL) was added NaH (60% in oil, 4.2 g, 105.72 mmol) at 0¡C
and, after having ceased hydrogen gas evolution, 2-bromomethyl-
IR (film): n = 3404 cmÐ1.
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FEATURE ARTICLE
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347
1H NMR (CDCl3, 300 MHz): d = 7.40 (1 H, t, J = 1.4 Hz), 6.36 (2
H, d, J = 1.4 Hz), 4.74 (1 H, dd, J = 5.5, 4.1 Hz), 3.98Ð3.92 (1 H,
m), 3.72 (1 H, dd, J = 10.4, 4.0 Hz), 3.61 (1 H, dd, J = 10.4, 4.9 Hz),
3.06 (1 H, d, J = 4.1 Hz), 2.72 (1 H, d, J = 6.3 Hz), 0.91 (9 H, s),
0.07 (6 H, s).
13C NMR (CDCl3, 75 MHz): d = 153.9, 142.3, 128.1, 110.3, 107.6,
73.1, 68.2, 63.9, 25.7, 18.1, Ð5.7.
(+)-(1S,5S,7R)-7-(2-Naphthylmethyloxymethyl)-6,8-dioxabicy-
clo[3.2.1]oct-3-en-2-one (11: P = 2-naphthylCH2)
To a stirred solution of 10 (P = 2-naphthylCH2) (4.61 g, 15.47
mmol) in CH2Cl2 (100 mL) was added MCPBA (70%, 4.19 g, 17.01
mmol) at 0 ûC and the mixture was stirred at r.t. for 3 h. The mixture
was filtered through a Celile pad and evaporated under reduced
pressure to give the crude pyran-3-one 12 (P = 2-naphthylCH2).
The crude 12, without purification, was then refluxed in benzene
(100 mL) in the presence of p-TsOH (29 mg, 0.15 mmol) for 10 h.
After cooling, the mixture was diluted with EtOAc (100 mL) and
the solution was washed with sat. aq NaHCO3 (3 × 10 mL) and brine
(10 mL), and dried (MgSO4). After evaporation of the solvent under
reduced pressure, the residue was chromatographed (silica gel,
100 g, elution with EtOAcÐhexane, 1:8 v/v) to give the bicyclic
enone 11 (P=2-naphthylCH2) (3.11 g, 68% from 10) as a colorless
prisms, mp 80Ð83 ûC: [a]D29 Ð156.16 (c = 1.2, CHCl3).
HRMS calcd for C13H23O3Si (M+ÐOH) 255.1417, found 255.1418.
The (+)-(1R,2S)-enantiomer 10 (P = TBS) was also prepared under
the same conditions using AD-mix-a in a comparable yield: [a]D25
+1.63 (c = 1.1, CHCl3), 99.6% ee (for dibenzoate) by hplc
(CHIRALCEL OD, elution with i-PrOHÐhexane 1:500 v/v).
(+)-(1S,2R)-1-(2-Furyl)-3-(2-naphthylmethyloxy)propane-1,2-
diol (10: P = 2-naphthyl CH2)
To a stirred solution of 9 (R = 2-naphthylCH2) (8.05 g, 30.49 mmol)
in t-BuOHÐH2O (1:1 v/v, 300 mL), MeSO2NH2 (2.9 g,
30.49 mmol), and AD-mix-b (39 g) was added at 0¡C and the mix-
ture was stirred at the same temperature for 46 h. The reaction was
quenched by addition of Na2SO3 (11.5 g, 91.47 mmol) and the mix-
ture was extracted with EtOAc (3 × 200 mL). The combined ex-
tracts were washed successively with 10% aq KOH (60 mL) and
brine (30 mL), and dried (MgSO4). After evaporation of the solvent
under reduced pressure, the residue was chromatographed (silica
gel 160 g, elution with EtOAcÐhexane, 1:2 v/v) to give the glycol
10 (P = 2-naphthylCH2) (6.69 g, 74%) as colorless needles, mp 83Ð
85 ûC: [a]D27 +24.06 (c = 1.0, CHCl3).
IR (Nujol): n = 1700 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.86Ð7.82 (3 H, m), 7.77 (1 H, s),
7.52Ð7.45 (3 H, m), 7.12 (1 H, dd, J = 9.9, 3.2 Hz), 6.09 (1 H, d, J
= 9.9 Hz), 5.83 (1 H, d, J = 3.2 Hz), 4.76 (2 H, s), 4.62 (1 H, t, J =
1.2 Hz), 4.04 (1 H, td, J = 5.5, 1.4 Hz), 3.67 (1 H, dd, J = 10.0, 5.6
Hz), 3.57 (1 H, dd, J = 10.0, 6.6 Hz).
HRMS calcd for C18H16O4 (M+) 296.1048, found 296.1027.
(+)-(1R,2S,5S,7R)-7-tert-Butyldimethylsiloxymethyl-6,8-dioxa-
bicyclo[3.2.1]oct-3-en-2-ol (13: P = TBS)
To a stirred mixture of 11 (P = TBS) (658 mg, 2.44 mmol) and
CeCl3á7H2O (1.09 g, 2.92 mol) in MeOH (25 mL) was added
NaBH4 (411 mg, 2.92 mmol) at 0¡C. After stirring for 25 min at the
same temperature, the solvent was removed under reduced pressure
and the residue was dissolved in EtOAc (30 mL) and the organic
layer was washed successively with H2O (5 mL) and brine (3 mL)
and dried (MgSO4). After evaporation of the solvent under reduced
pressure, the residue was chromatographed (silica gel, 15 g, elution
with EtOAcÐhexane, 1:10 v/v) to give the endo-alcohol 13 (P =
TBS) (654 mg, 99%) as a colorless oil: [a]D28 +1.57 (c = 1.0, CHCl3).
IR (Nujol): n = 3379 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.85Ð7.81 (3 H, m), 7.75 (1 H, s),
7.52Ð7.43 (3 H, m), 7.36 (1 H, t, J = 1.1 Hz), 6.31Ð6.34 (2 H, m),
4.78 (1 H, d, J = 4.7 Hz), 4.74 (1 H, d, J = 11.7 Hz), 4.67 (1 H, d, J
= 11.7 Hz), 4.16Ð4.09 (1 H, m), 3.62 (1 H, dd, J = 9.8, 3.8 Hz), 3.53
(1 H, dd, J = 9.8, 5.5 Hz), 2.95 (1 H, d, J = 4.7 Hz), 2.76 (1 H, d, J
= 5.2 Hz).
HRMS calcd for C18H18O4 (M+) 298.1205, found 298.1206.
IR (film): n = 3456 cmÐ1.
(Ð)-(1S,5S,7R)-7-tert-Butyldimethylsiloxymethyl-6,8-dioxabicy-
clo[3.2.1]oct-3-en-2-one (11: P = TBS)
1H NMR (CDCl3, 300 MHz): d = 5.91 (1 H, ddd, J = 9.7, 3.2,
1.8 Hz), 5.72 (1 H, dtd, J = 9.7, 2.0, 0.8 Hz), 5.49 (1 H, d, J = 3.2
Hz), 4.80Ð4.75 (1 H, m), 4.32 (1 H, ddd, J = 7.1, 5.2, 1.6 Hz), 4.27
(1 H, dt, J = 4.7, 1.6 Hz), 3.74 (1 H, dd, J = 10.4, 5.2 Hz), 3.58 (1
H, dd, J = 10.4, 7.1 Hz), 1.75 (1 H, br.d, J = 6.0 Hz), 0.89 (9 H, s),
0.07 (6 H, s).
To a stirred solution of 10 (P = TBS) (3.61 g, 13.2 mmol) in CH2Cl2
(80 mL) was added MCPBA (70%, 3.59 g, 14.6 mmol) at 0¡C in the
presence of NaHCO3 (2.23 g, 26.5 mmol) and the mixture was
stirred at r.t. for 3 h. The mixture was filtered through a Celile pad
and evaporated under the reduced pressure to give the crude pyran-
3-one 12 (P = TBS).
HRMS calcd for C9H15O4Si (MÐC4H9) 215.0740, found 215.0713.
The crude 12, without purification, was then refluxed in benzene
(80 mL) in the presence of p-toluenesulfonic acid (p-TsOH) (25 mg,
0.13 mmol) with removal of water using a DeanÐStark apparatus.
After 5 h, the mixture in EtOAc (100 mL) was washed successively
with sat. aq NaHCO3 (3 × 20 mL), and brine (10 mL), dried
(MgSO4), and evaporated under reduced pressure. The residue was
chromatographed (silica gel, 75 g, elution with EtOAcÐhexane,
1:20 v/v) to give the bicyclic enone 11 (P = TBS) (2.47 g, 69% from
10) as a pale yellow oil: [a]D28 Ð187.01 (c = 1.0, CHCl3).
The (Ð)-(1S,2R,5R,7S)-enantiomer 13 (P = TBS) was also prepared
under the same conditions in a comparable yield: [a]D24 Ð1.30 (c =
1.1, CHCl3).
(+)-(1R,2S,5S,7R)-2-Benzyloxy-7-tert-butyldimethylsiloxy-
methyl-6,8-dioxabicyclo[3.2.1]oct-3-ene (14: P = TBS)
To a stirred solution of 13 (P = TBS) (1.39 g, 5.09 mmol) in THF
(40 mL) was added NaH (60% in oil, 265 mg, 6.62 mol) at 0¡C and,
after 10 min, BnBr (848 µL, 7.13 mmol) was added and the mixture
was refluxed for 12 h. The mixture was cooled to 0¡C and was again
treated with NaH (60% in oil, 143 mg, 3.57 mmol) and MeOH
(144 µL, 3.57 mmol) for 15 min to destroy the excess BnBr. The
mixture was then treated with H2O (10 mL) and extracted with
EtOAc (100 mL). The extract was washed with brine (5 mL), dried
(MgSO4), evaporated, and chromatographed (silica gel 30 g, elution
with EtOAcÐhexane, 1:100 v/v) to give the benzyl ether 14 (P =
TBS) (1.69 g, 92%) as a colorless oil: [a]D28 +12.25 (c = 1.2, CHCl3).
IR (film): n = 1701 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.12 (1 H, dd, J = 9.8, 3.2 Hz),
6.08 (1 H, dd, J = 9.8, 1.1 Hz), 5.79 (1 H, d, J = 3.2 Hz), 4.61 (1 H,
t, J = 1.1 Hz), 3.88Ð3.77 (2 H, m), 3.58 (1 H, dd, J = 9.9, 7.1 Hz),
0.90 (9 H, s), 0.08 (3 H, s), 0.07 (3 H, s).
HRMS calcd for C12H19O4Si (MÐCH3) 255.1053, found 255.1008.
The (+)-(1R,5R,7S)-enantiomer 11 (P = TBS) was also prepared un-
der the same conditions a comparable yield: [a]D25 +186.10 (c = 1.0,
CHCl3).
1H NMR (CDCl3, 300 MHz): d = 7.36Ð7.29 (5 H, m). 5.92 (1 H,
ddd, J = 9.7, 3.1, 1.6 Hz), 5.76 (1 H, dt, J = 9.7, 1.9 Hz), 5.47 (1 H,
d, J = 3.1 Hz), 4.68 (1 H, d, J = 11.8 Hz), 4.56 (1 H, d, J = 11.8 Hz),
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348
M. Takeuchi et al.
FEATURE ARTICLE
4.53Ð4.45 (3 H, m), 3.74 (1 H, dd, J = 10.2, 4.9 Hz), 3.54 (1 H, dd,
J = 10.2, 8.2 Hz), 0.89 (9 H, s), 0.08 (3 H, s), 0.06 (3 H, s).
HRMS calcd for C20H30O4Si (M+) 362.1913, found 362.1930.
a r.t. for 2 h. The mixture was washed successively with H2O
(20 mL) and brine (10 mL), and dried (MgSO4). After evaporation
of the solvent under reduced pressure, the residue was chromato-
graphed (silica gel, 135 g, elution with EtOAcÐhexane 1:2 v/v) to
give the primary alcohol 17 (3.02 g, 94%) as a colorless oil: [a]D31
+14.11 (c = 1.1, CHCl3).
The (Ð)-(1S,2R,5R,7S)-enantiomer 14 (P = TBS) was also prepared
under the same conditions in a comparable yield: [a]D27 Ð11.58 (c =
1.1, CHCl3).
IR (film): n = 3482 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.38Ð7.28 (15 H, m), 5.31 (1 H,
d, J = 1.9 Hz), 4.81 (1 H, d, J = 12.4 Hz), 4.80 (1 H, d, J = 12.4 Hz),
4.71 (1 H, d, J = 12.1 Hz), 4.66 (1 H, d, J = 12.1 Hz), 4.64 (1 H, d,
J = 12.4 Hz), 4.60 (1 H, d, J = 12.4 Hz), 4.20Ð4.17 (2 H, m), 4.01Ð
3.95 (1 H, m), 3.74Ð3.70 (2 H, m), 3.46 (2 H, d, J = 5.8 Hz), 1.71 (1
H, br s).
(Ð)-(1R,2S,3R,4S,5S,7R)-2-Benzyloxy-7-tert-butyldimethylsilÐ
oxymethyl-6,8-dioxabicyclo[3.2.1]octane-3,4-diol (15: P = TBS)
To a stirred solution of 14 (P = TBS) (2.93 g, 8.08 mmol), NMO
(1.42 g, 12.1 mmol) in acetoneÐH2O (1:1 v/v, 60 mL) was added
OsO4 (0.1967 M in THF, 4.09 mL, 0.81 mmol) at 0¡C and the mix-
ture was stirred for 3 h at the r.t. The reaction was quenched by ad-
dition of sat. aq Na2SO3 (5 mL) and the organic layer was extracted
with EtOAc (2 × 50 mL). The extract was washed with brine
(5 mL), dried (MgSO4), evaporated under reduced pressure, and
chromatographed (silica gel, 60 g, elution with EtOAcÐhexane, 1:2
v/v) to give the glycol 15 (P = TBS) (3.02 g, 94%) as an amorphous
solid: [a]D26 Ð41.12 (c = 1.0, CHCl3).
HRMS calcd for C21H23O6 (M+ÐC7H7) 371.1495, found 371.1472.
The (Ð)-(1S,2R,3R,4R,5R,7S)-enantiomer 16 (P = TBS) was also
prepared under the same conditions in a comparable yield: [α]D28
Ð14.02 (c = 1.0, CHCl3).
(Ð)-(1R,2S,3S,4S,5S,7R)-2,3,4-Trisbenzyloxy-7-iodomethyl-6,8-
dioxabicyclo[3.2.1]octane (19)
IR (film): n = 3400 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.37Ð7.30 (5 H, m), 5.42 (1 H, d,
J = 1.9 Hz), 4.73 (1 H, d, J = 11.7 Hz), 4.65 (1 H, d, J = 11.7 Hz),
4.42 (1 H, d, J = 4.1 Hz), 4.16 (1 H, dd, J = 8.6, 5.4 Hz), 3.87Ð3.79
(2 H, m), 3.64 (1 H, dd, J = 8.2, 4.1 Hz), 3.58 (1 H, dd, J = 9.9,
5.4 Hz), 3.39 (1 H, dd, J = 9.9, 8.6 Hz), 2.48 (1 H, br s), 2.20 (1 H,
br s), 0.89 (9 H, s), 0.07 (3 H, s), 0.06 (3 H, s).
To a stirred solution of 17 (P = TBS) (1.65 g, 3.57 mmol) and Et3N
(1.49 mL, 10.7 mmol) in CH2Cl2 (35 mL) was added methanesulfo-
nyl chloride (MsCl) (414 µL, 5.35 mmol) at 0¡C and the mixture
was stirred at r.t. for 3 h. The mixture was washed with H2O (5 mL),
brine (3 mL), dried (MgSO4), and evaporated under reduced pres-
sure to give the crude mesylate 18. Without purification, the crude
18 was refluxed with LiI (4.77 g, 35.7 mmol) in THF (35 mL) for
6 h. After cooling, the mixture was diluted with EtOAc (50 mL) and
was washed successively with 10% aq Na2S2O3 (10 mL), sat. aq
NaHCO3 (10 mL) and brine (5 mL), and dried (MgSO4). After evap-
oration of the solvent under reduced pressure, the residue was chro-
matographed (silica gel, 35 g, elution with EtOAcÐhexane, 1:20 v/
v) to give the iodide 19 (2.01 g, 99% from 16) as a colorless oil:
[a]D28 Ð7.70 (c = 1.1, CHCl3).
1H NMR (CDCl3, 300 MHz): d = 7.41Ð7.28 (15 H, m), 5.34 (1 H,
d, J = 1.9 Hz), 4.80 (1 H, d, J = 12.2 Hz), 4.75 (2 H, s), 4.71 (1 H,
d, J = 12.1 Hz), 4.65 (1 H, d, J = 12.1 Hz), 4.59 (1 H, d, J = 12.2
Hz), 4.41 (1 H, d, J = 14.4 Hz), 4.38 (1 H, dd, J = 9.5, 5.8 Hz), 4.01Ð
3.94 (1 H, m), 3.71Ð3.66 (2 H, m), 3.10 (1 H, dd, J = 9.5, 5.8 Hz),
3.01 (1 H, dd, J = 9.5 Hz).
HRMS calcd for C16H23O6Si (MÐC4H9) 339.1264, found 339.1277.
The (+)-(1S,2R,3S,4R,5R,7S)-enantiomer 15 (P = TBS) was also
prepared under the same conditions in a comparable yield: [a]D31
+41.44 (c = 1.0, CHCl3).
(+)-(1R,2S,3S,4S,5S,7R)-2,3,4-Trisbenzyloxy-7-tert-butyldi-
methylsiloxymethyl-6,8-dioxabicyclo[3.2.1]octane (16: P = TBS)
To a stirred solution of the glycol 15 (P = TBS) (435 mg,
1.20 mmol) in THF (9 mL) was added NaH (60% in oil, 220 mg,
5.49 mmol) at 0¡C. After 10 min, BnBr (784 µL, 6.59 mmol) was
added to the mixture and the mixture was refluxed for 5 h. After
cooling, the mixture was treated with NaH (60% in oil, 62 mg,
1.54 mmol) and MeOH (62 µl, 1.54 mmol) for 15 min to quench the
excess BnBr. The mixture was diluted with EtOAc (30 mL) and
washed with H2O (5 mL), brine (3 mL) and dried (MgSO4). Evapo-
ration of the solvent under reduced pressure, followed by chroma-
tography (silica gel 10 g, elution with EtOAcÐhexane, 1:40 v/v) to
give the trisbenzyl ether 16 (P = TBS) (581 mg, 92%) as a colorless
oil: [a]D28 +3.38 (c = 1.0, CHCl3).
HRMS calcd for C21H22IO5 (M+ÐC7H7) 481.0471, found 481.0506.
The (+)-(1S,2R,3R,4R,5R,7S)-enantiomer 19 was also prepared un-
der the same conditions in a comparable yield: [a]D30 +7.56 (c = 1.1,
CHCl3).
1H NMR (CDCl3, 300 MHz): d = 7.37Ð7.27 (15 H, m), 5.26 (1 H,
d, J = 1.9 Hz), 4.80 (1 H, d, J = 12.4 Hz), 4.73 (1 H, d, J = 11.4 Hz),
4.72 (1 H, d, J = 11.8 Hz), 4.69 (1 H, d, J = 11.4 Hz), 4.65 (1 H, d,
J = 11.8 Hz), 4.60 (1 H, d, J = 12.4 Hz), 4.36 (1 H, d, J = 4.1 Hz),
4.13 (1 H, dd, J = 8.4, 5.4 Hz), 4.00 (1 H, dd, J = 8.5, 4.1 Hz), 3.75Ð
3.68 (2 H, m), 3.52 (1 H, dd, J = 9.8, 5.4 Hz), 3.36 (1 H, dd, J = 9.8,
8.4 Hz), 0.88 (9 H, s), 0.05 (3 H, s), 0.04 (3 H, s).
(2R/S,3S,4S,5S,6S)-3,4,5-Trisbenzyloxy-6-vinyloxan-2-ol (20)
A solution of the iodide 19 (2.21 g, 3.86 mmol) in HOAc (40 mL)
was stirred with activated Zn powder (12.6 g, 193 mmol) at r.t. for
3 h. The mixture was filtered and the filtrate was diluted with
EtOAc (100 mL) and the mixture was washed successively with
H2O (10 mL), sat. aq NaHCO3 (10 mL), brine (5 mL) and dried
(MgSO4). After evaporation of the solvent under reduced pressure,
the residue was chromatographed (silica gel, 45 g, elution with
EtOAcÐhexane, 1:5 v/v) to give the hemiacetal 20 (1.67g, 97%) as
a colorless oil.
HRMS calcd for C27H37O6Si (M+ÐC7H7) 485.2359, found
485.2329.
The (Ð)-(1S,2R,3R,4R,5R,7S)-enantiomer 16 (P = TBS) was also
prepared under the same conditions in a comparable yield: [α]D29
Ð3.03 (c = 1.2, CHCl3).
IR (film): n = 3470 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.39Ð7.25 (15 H, m), 5.89 (0.5 H,
ddd, J = 17.3, 10.6, 6.2 Hz), 5.86 (0.5 H, ddd, J = 17.3, 10.6,
5.8 Hz), 5.37 (0.5 H, dt, J = 17.3, 1.5 Hz), 5.32 (0.5 H, dt, J = 17.3,
1.5 Hz), 5.22 (0.5 H, dt, J = 10.6, 1.5 Hz), 5.20 (0.5 H, dt, J = 10.6,
1.5 Hz), 5.18Ð5.14 (1.5 H, m), 4.79Ð4.32 (7 H, m), 3.86 (0.5 H, s),
3.85 (0.5 H, s), 3.76 (0.5 H, t, J = 3.3 Hz), 3.56 (0.5 H, dd, J = 8.0,
3.0 Hz), 3.46 (0.5 H, br.t, J = 1.8 Hz), 3.35 (0.5 H, dd, J = 3.9,
1.5 Hz), 3.11 (0.5 H, d, J = 6.0 Hz).
(+)-(1R,2S,3S,4S,5S,7R)-2,3,4-Trisbenzyloxy-7-hydroxymethyl-
6,8-dioxabicyclo[3.2.1]octane (17)
To a stirred solution of 16 (P = TBS) (6.53 g, 11.3 mmol) in THF
(100 mL) was added tetrabutylammonium fluoride (TBAF) in THF
(1.0 M, 17.0 mL, 17.0 mmol) at 0 ûC and the mixture was stirred at
Synthesis 1999, No. 2, 341–354 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE
Back to the Sugars
349
HRMS calcd for C21H23O5 (M+ÐC7H7) 355.1546, found 355.1527.
The filtrate was dried (MgSO4), evaporated under reduced pressure,
and chromatographed (silica gel, 9 g, elution with EtOAcÐhexane,
1:5 v/v) to give the diol 24 (405 mg, 90%) as a colorless oil: [α]D27
Ð5.23 (c = 1.0, CHCl3).
The (2R/S,3R,4R,5R,6R)-enantiomer 20 was also prepared under
the same conditions in a comparable yield.
IR (neat): n = 3438 cmÐ1.
(2R/S,3S,4S,5S,6S)-2,3,4,5-Tetrakisbenzyloxy-6-vinyloxane
(21)
1H NMR (CDCl3, 300 MHz): d = 7.37Ð7.25 (15 H, m). 5.93 (1 H,
ddd, J = 17.2, 10.6, 5.8 Hz), 5.33 (1 H, d, J = 17.2 Hz), 5.19 (1 H,
d, J = 10.6 Hz), 4.76Ð4.53 (6 H, m), 4.36Ð4.25 (1 H, m), 3.91Ð3.74
(4 H, m), 3.62 (1 H, dd, J = 5.2, 3.6 Hz), 2.79 (1 H, br.d, J = 5.2 Hz),
2.31 (1 H, br.s).
A mixture of the hemiacetal 20 (505 mg, 1.13 mmol) in benzyl al-
cohol (1.17 mL, 11.3 mmol) in benzene (10 mL) was refluxed for
6 h in the presence of p-TsOH (2 mg, 0.01 mmol) using a DeanÐ
Stark apparatus. The mixture diluted with EtOAc (20 mL) was
washed with sat. aq NaHCO3 (5 mL), brine (3 mL), dried (MgSO4),
evaporated under reduced pressure, and chromatographed (silica
gel 15 g, elution with EtOAcÐhexane, 1:40 v/v) to give the tetraben-
zyl ether 21 (516 mg, 85%) as a colorless oil.
1H NMR (CDCl3, 300 MHz): d = 7.35Ð7.25 (20 H, m), 5.90 (1 H,
ddd, J = 17.4, 10.5, 5.9 Hz), 5.34 (1 H, dt, J = 17.4, 1.5 Hz), 5.20 (1
H, dt, J = 10.5, 1.5 Hz), 5.05Ð4.98 (1 H, m), 5.00 (1 H, dt, J =
12.2 Hz), 4.87 (1 H, d, J = 12.2 Hz), 4.73 (1 H, dt J = 12.2 Hz), 4.65
(1 H, d, J = 12.2 Hz), 4.62 (1 H, d, J = 12.2 Hz), 4.52 (1 H, d, J =
12.2 Hz), 4.40 (1 H, d, J = 12.2 Hz), 4.39Ð4.34 (1 H, m), 4.34 (1 H,
d, J = 12.2 Hz), 3.77 (1 H, t, J = 3.4 Hz), 3.71(1 H, dd, J = 8.0,
3.3 Hz), 3.35 (1 H, dd, J = 3.8, 1.6 Hz).
FABMS: m/z = 499 (M++1).
(3S,4R,5R,6R)-3,4,5,6,7-Pentabenzyloxyhept-1-ene (25)
A diol 24 (1 g, 2.23 mmol) was treated with NaH (60% in oil,
356 mg, 8.92 mmol) and BnBr (1.3 mL, 11.15 mmol) in THF
(30 mL) in the presence of Bu4NI (82 mg, 0.22 mmol) as for the
preparation of 16. After workup and evaporating the solvent under
reduced pressure the residue was chromatographed (silica gel, 20 g,
elution with Et2OÐhexane, 1:10 v/v) to give 25 (1.3 g, 93%) as a col-
orless oil: [a]D29 +15.66 (c = 1.0, CHCl3).
1H NMR (CDCl3, 300 MHz): d = 7.34Ð7.22 (25 H, m). 5.83 (1 H,
ddd, J = 17.5, 10.3, 7.5 Hz), 5.26 (1 H, dd, J = 10.3, 1.6 Hz), 5.17
(1 H, dt, J = 17.5, 0.8 Hz), 4.79 (1 H, d, J = 11.5 Hz), 4.73 (1 H, d,
J = 11.8 Hz), 4.64 (1 H, d, J = 11.8 Hz), 4.63 (1 H, d, J = 11.5 Hz),
4.60 (1 H, d, J = 11.8 Hz), 4.59 (1 H, d, J = 11.8 Hz), 4.50 (1 H, d,
J = 11.8 Hz), 4.45 (1 H, d, J = 12.2 Hz), 4.41 (1 H, d, J = 12.2 Hz),
4.34 (1 H, d, J = 11.8 Hz), 4.09 (1 H, dd, J = 7.7, 6.0 Hz), 3.95 (1
H, t, J = 4.8 Hz), 3.88Ð3.82 (2 H, m), 3.75 (1 H, dd, J = 5.8, 4.9 Hz),
3.73Ð3.65 (1 H, m).
FABMS: m/z = 535 (M+ Ð1).
The (2R/S,3R,4R,5R,6R)-enantiomer was also prepared under the
same conditions in a comparable yield.
(2R/S,3S,4S,5S,6S)-2,3,4,5-Tetrakisbenzyloxy-6-hydroxymeth-
yloxane (22)
To a stirred solution of the alkene 21 (323 mg, 0.60 mmol) in
MeOHÐCH2Cl2 (1:1 v/v, 6 mL) was introduced ozone at Ð78¡C for
10 min. After excess ozone was removed by introduction of Ar,
NaBH4 (228 mg, 6.02 mmol) was added to the mixture and the mix-
ture was stirred at r.t. for 20 min. After evaporation of the solvent
under reduced pressure, the residue was chromatographed (silica
gel, 10 g, elution with EtOAcÐhexane, 1:4 v/v) to give the alcohol
22 (311 mg, 96%) as a colorless oil.
FABMS: m/z = 629 (M++1).
(2R,3S,4R,5R)-2,3,4,5,6-Pentabenzyloxyhept-1-al (26)
To a stirred solution of OsO4 (0.1967 M in THF, 324 µL,
0.06 mmol), NMO (228 mg, 1.91 mmol) in acetoneÐH2O (1:1 v/v,
15 mL) was added 25 (800 mg, 1.27 mmol) at 0¡C. After 2 h at the
r.t., the reaction was quenched by addition of sat. aq Na2SO3 (2 mL)
and, after 10 min, the mixture was extracted with EtOAc (2 × 50
mL). The extract was washed successively with H2O (10 mL) and
brine (5 mL), dried (MgSO4), and evaporated under reduced pres-
sure. The residue was then dissolved in THFÐH2O (2:1 v/v, 15 mL)
and was then treated with NaIO4 (834 mg, 3.81 mmol) at r.t. for 1 h
with stirring. The mixture diluted in EtOAc (50 mL) was washed
successively with H2O (10 mL) and brine (5 mL), dried (MgSO4),
and evaporated under reduced pressure. The residue was chromato-
graphed (silica gel, 15 g, elution with Et2OÐhexane, 1:3 v/v) to give
26 (662 mg, 83% from 25) as a colorless oil: [a]D29 +8.27 (c = 1.0,
CHCl3).
IR (film): n = 3472 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.44Ð7.09 (20 H, m), 5.04Ð4.17
(9 H, m), 3.95 (1 H, ddd, J = 6.3, 4.7, 1.6 Hz), 3.88Ð3.78 (2 H, m),
3.68 (1 H, dd, J = 8.0, 3.3 Hz), 3.42Ð3.59 (1 H, m), 3.73 (1 H, dd, J
= 3.8, 1.6 Hz), 1.76 (1 H, br.s).
HRMS calcd for C27H28O5 (M+ÐC7H8O) 432.1937, found 432.1905.
The (2R/S,3S,4S,5S,6S)-enantiomer 22 was also prepared under the
same conditions in a comparable yield.
(+)-L-Gulose (23)
IR (film): n = 1727 cmÐ1.
A solution of the tetrabenzyl ether 22 (311 mg, 0.58 mmol) in
MeOH (6 mL) was hydrogenated on Pd(OH)2 (10 mg) at r.t. for
144 h. The mixture was diluted with MeOH (20 mL) and filtered
through a Celite pad to remove the catalyst. The filtrate was evapo-
rated under reduced pressure and chromatographed (silica gel, 10 g,
elution with EtOAcÐMeOHÐH2O, 15:2:1 v/v) to give the L-gulose
(23) (103 mg, 99%) as an amorphous solid: [a]D31 +20.94 (c = 1.0,
H2O) [lit. [a]D25 +16.0 (c = 1.28, H2O), [a]D Ð20 (for D-gulose)].
Spectral data (IR, 1H NMR) and tlc were identical with those of an
authentic material. (Ð)-D-Gulose (23) was also prepared under the
same conditions in a comparable yield: [a]D31 Ð21.09 (c = 1.1, H2O).
1H NMR (CDCl3, 300 MHz): d = 9.72 (1 H, s), 7.35Ð7.15 (25 H, m),
4.78 (1 H, d, J = 12.1 Hz), 4.66 (1 H, d, J = 11.8 Hz), 4.59Ð4.39 (8
H, m), 4.12 (1 H, dd, J = 6.9, 3.4 Hz), 4.03 (1 H, dd, J = 6.7, 3.6 Hz),
3.91Ð3.80 (3 H, m), 3.70Ð3.27 (1 H, m).
HRMS calcd for C34H35O6 (M+ÐC7H7) 539.2432, found 539.2458.
(+)-D-Glucose (27)
A solution of the tetrabenzyl ether 26 (390 mg, 618 mmol) in
MeOH (15 mL) was hydrogenated on Pd(OH)2 (40 mg) at r.t. for
120 h. As treated for 23 D-glucose 27 (93 mg, 83%) was obtained
after chromatography (silica gel, 8 g, elution with EtOAcÐMeOHÐ
H2O, 15:2:1 v/v) as an amorphous solid: [a]D29 +43.37 (c = 1.3, H2O)
[lit. [a]D21 Ð47.2 (c = 0.83, H2O), [a]D Ð51.4 (for L-glucose)].
(3S,4R,5R,6R)-3,7-Dihydroxy-4,5,6-tribenzyloxyhept-1-ene (24)
To a stirred solution of hemiacetal 20 (448 mg, 1.00 mmol) in THF
(10 mL) was added LiAlH4 (76 mg, 2.00 mmol) at r.t.. After stirring
for 3 h at the same temperature, the mixture was treated with 30 %
NH4OH (2 mL) and the mixture was filtered through a Celite pad.
Spectral data (IR, 1H NMR) and tlc were identical with those of an
authentic material.
Synthesis 1999, No. 2, 341–354 ISSN 0039-7881 © Thieme Stuttgart á New York

350
M. Takeuchi et al.
FEATURE ARTICLE
(3S,4S,5S,6S)-3,4,5-Trisbenzyloxy-6-vinyloxan-2-one (28)
A solution of 20 (310 mg, 0.70 mmol), NMO (163 mg, 1.40 mmol),
4 A sieves (372 mg) and TPAP (24 mg, 0.07 mmol) in CH2Cl2
(7.0 mL) was stirred at r.t. for 1.5 h. After filtration, the filtrate was
evaporated under reduced pressure and the residue was chromato-
graphed (silica gel, 6 g, elution with EtOAcÐhexane, 1:5 v/v) to give
28 (259 mg, 84%) as a colorless oil: [a]D27 Ð96.79 (c = 1.2, CHCl3).
hexane, 1:10 v/v) to give 31 (410 mg, 88%) as a colorless crystalline
solid, mp 44Ð46¡C.
1H NMR (CDCl3, 300 MHz): d = 7.42Ð7.03 (20 H, m), 6.46Ð6.31
(0.25 H, m), 6.16Ð6.04 (0.75 H, m), 5.50Ð5.29 (2 H, m), 4.92Ð4.48
(9.75 H, m), 4.37Ð4.31 (0.25 H, m), 4.10Ð4.04 (0.25 H, m), 3.76Ð
3.68 (1.5 H, m), 3.65Ð3.59 (0.25 H, m), 3.55Ð3.48 (1 H, m).
HRMS calcd for C28H29O5 (M+ Ð C7H7) 445.2014, found 445.1989.
IR (film): n = 1754 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.39Ð7.25 (15 H, m), 5.92 (1 H,
ddd, J = 17.3, 10.5, 6.7 Hz), 5.38 (1 H, dt, J = 17.3, 1.1 Hz), 5.29 (1
H, dt, J = 10.5, 1.1 Hz), 5.13Ð5.09 (2 H, m), 4.89 (1 H, d, J =
12.1 Hz), 4.66 (1 H, d, J = 12.1 Hz), 4.59 (1 H, d, J = 12.1 Hz), 4.42
(1 H, d, J = 11.8 Hz), 4.40 (1 H, d, J = 2.7 Hz), 4.33 (1 H, d, J =
11.8 Hz), 3.96 (1 H, dd, J = 4.4, 3.0 Hz), 3.61 (1 H, dd, J = 4.4, 2.7
Hz).
(2R/S,3R,4S,5S,6S)-2,3,4,5-Tetrakisbenzyloxy-6-hydroxymeth-
yloxane (32)
To a solution of 31 (500 mg, 0.93 mmol) in MeOHÐCH2Cl2 (1:1 v/
v, 30 mL) was introduced ozone at Ð78 ûC for 10 min. After 10 min,
NaBH4 (353 mg, 9.33 mmol) was added at the same temperature
and the mixture was warmed to r.t. After evaporation of the solvent,
the residue was chromatographed (silica gel, 10 g, elution with
EtOAcÐhexane, 1:4 v/v) to give 32 (411 mg, 82%) as a colorless
crystalline solid, mp 90Ð92 ûC.
HRMS calcd for C21H21O5 (MÐC7H7) 353.1389, found 353.1347.
(3R,4S,5S,6S)-3,4,5-Trisbenzyloxy-6-vinyloxan-2-one (29)
A solution of 28 (338 mg, 0.76 mmol) and DABCO (128 mg,
1.14 mmol) in benzene (8 mL) was stirred at r.t. for 15 h. The mix-
ture, after diluted with EtOAc (30 mL), was washed successively
with H2O (5 mL) and brine (3 mL), dried (MgSO4), and evaporated
under reduced pressure. The residue was chromatographed (silica
gel, 6 g, elution with EtOAcÐhexane, 1:2 v/v) to give a crystalline
solid which was recrystallized to give 29 (249 mg, 74%) as color-
less needles, mp 117Ð119 ûC: [a]D27 +32.02 (c = 1.1, CHCl3).
IR (Nujol): n = 3344 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.39Ð7.26 (25 H, m), 4.97Ð4.49
(9 H, m), 4.14Ð3.47 (6 H, m), 2.05Ð2.02 (1 H, m).
HRMS calcd for C27H29O6 (M+ÐC7H7) 449.1963, found 449.1952.
(Ð)-L-Idose (33)
A solution of the tetrabenzyl ether 32 (400 mg, 741 mmol) in
MeOH (15 mL) was hydrogenated on Pd(OH)2 (40 mg) at r.t. for
144 h. As treated for 23 L-idose 33 (106 mg, 80%) was obtained af-
ter chromatographed (silica gel, 8 g, elution with EtOAcÐMeOHÐ
H2O, 15:2:1 v/v) as an amorphous solid: [a]D29 Ð12.35 (c = 1.0, H2O)
[lit. [a]D25 Ð10.6 (c = 0.98, H2O), [a]D +15.8 (for D-idose)].
IR (Nujol): n = 1745 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.44Ð7.23 (15 H, m), 6.00 (1 H,
ddd, J = 17.3, 10.7, 6.6 Hz), 5.41 (1 H, dt, J = 17.3, 1.1 Hz), 5.32 (1
H, dt, J = 10.7, 1.1 Hz), 5.06 (1 H, d, J = 11.5 Hz), 4.85 (1 H, dd, J
= 6.6, 1.5 Hz), 4.66 (1 H, d, J = 11.5 Hz), 4.61 (1 H, d, J = 11.8 Hz),
4.57 (1 H, d, J = 12.1 Hz), 4.54 (1 H, d, J = 11.8 Hz), 4.41 (1 H, d,
J = 12.1 Hz), 4.18 (1 H, d, J = 6.3 Hz), 3.87 (1 H, dd, J = 6.3,
1.5 Hz), 3.64 (1 H, t, J = 1.5 Hz).
Spectral data (IR, 1H NMR) and tlc were identical with those of an
authentic material.
(+)-(1S,3R,4S,5S,7R)-3,4-Epoxy-7-(2-naphthylmethyloxymeth-
yl)-6,8-dioxabicyclo[3.2.1]octan-2-one (34: P = 2-naphthylCH2)
To a stirred solution of the enone 11 (P = 2-naphthylCH2) (756 mg,
2.55 mmol) in THF (15 mL) and 0.5 N NaOH (2.6 mL, 1.28 mmol)
was added 30% H2O2 (434 µL, 3.83 mmol) at 0¡C. After stirring for
30 min at r.t., the mixture was diluted with EtOAc (20 mL) and was
washed with H2O (5 mL) and brine (3 mL), and dried (MgSO4). Af-
ter evaporation of the solvent under reduced pressure, a crystalline
residue was recrystallized from Et2O to give the oxo epoxide 34 (P
= 2-naphthylCH2) (695 mg, 87%) as a colorless crystals, mp 136Ð
139¡C: [a]D28 +11.68 (c = 1.0, CHCl3).
HRMS calcd for C21H21O5 (M+ÐC7H7) 353.1389, found 353.1404.
(2R/S,3R,4S,5S,6S)-3,4,5-Trisbenzyloxy-6-vinyloxan-2-ol (30)
To a stirred solution of 29 (55 mg, 0.12 mmol) in CH2Cl2 (2 mL)
was added DIBAL (1.5 M in toluene, 140 µL, 0.21 mmol), at Ð78¡C
and the stiring was continued for 2 h at the same temperature. The
mixture was diluted with Et2O (10 mL) and the reaction was
quenched by addition of H2O (140 µL) and dried (MgSO4). The sol-
vent was removed under reduced pressure and the residue was chro-
matographed (silica gel, 1 g, elution with EtOAcÐhexane, 1:5 v/v)
to give 30 (53 mg, 96%) as a colorless oil.
IR (Nujol): n = 1738 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.86Ð7.83 (3 H, m), 7.75 (1 H, s),
7.51Ð7.43 (3 H, m), 5.89 (1 H, d, J = 0.5 Hz), 4.72 (2 H, s), 4.52 (1
H, t, J = 1.4 Hz), 4.14Ð4.10 (1 H, m), 3.57 (1 H, dd, J = 9.9, 5.8 Hz),
3.47 (1 H, dd, J = 3.6, 1.4 Hz), 3.45 (1 H, dd, J = 9.9, 6.9 Hz), 3.36Ð
3.34 (1 H, m).
IR (film): n = 3407 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.39Ð7.15 (15 H, m), 6.11 (0.7 H,
ddd, J = 17.3, 10.7, 6.0 Hz), 6.04 (0.3 H, ddd, J = 17.3, 10.7,
6.9 Hz), 5.43 (0.7 H, dt, J = 17.3, 1.5 Hz), 5.34 (0.3 H, dt, J = 17.3,
1.1 Hz), 5.32 (0.7 H, dt, J = 10.7, 1.5 Hz), 5.21 (0.3 H, dt, J = 10.7,
1.1 Hz), 5.14 (0.7 H, dd, J = 7.4, 4.7 Hz), 4.96 (0.3 H, dd, J = 12.4,
2.2 Hz), 4.76Ð4.46 (6 H, m), 4.35 (0.7 H, d, J = 1.6 Hz), 4.30 (0.3
H, br d, J = 6.3 Hz), 3.85 (0.3 H, d, J = 12.1 Hz), 3.75Ð3.69 (1 H,
m), 3.59Ð3.51 (1.4 H, m), 3.40Ð3.36 (1 H, m), 3.29Ð3.27 (0.3 H, m).
HRMS calcd for C18H16O5 (M+) 312.0998, found 312.1013.
(Ð)-(1R,2S,3S,4S,5S,7R)-3,4-Epoxy-2-hydroxy-7-(2-naphthyl-
methyloxymethyl)-6,8-dioxabicyclo[3.2.1]octane (38)
To a stirred solution of the oxo epoxide 34 (P = 2-naphthylCH2)
(558 mg, 1.79 mmol) and CeCl3á7H2O (800 mg, 2.15 mmol) in
MeOH (10 mL) was added NaBH4 (81 mg, 2.15 mmol) at 0¡C and
the stirring was continued for 25 min at the same temperature. After
dilution with EtOAc (20 mL) the mixture was washed successively
with H2O (5 mL) and brine (3 mL), and dried (MgSO4). After evap-
oration of the solvent under reduced pressure, the residue was chro-
matographed (silica gel, 10 g, elution with EtOAcÐhexane, 1:3 v/v)
to give the endo-alcohol 38 (529 mg, 94%) as colorless needles, mp
114Ð116¡C: [a]D27 Ð16.64 (c = 1.1, CHCl3).
FABMS: m/z = 445 (M+ Ð 1).
(2R/S,3R,4S,5S,6S)-2,3,4,5-Tetrakisbenzyloxy-6-vinyloxane (31)
A mixture of 30 (387 mg, 0.87 mmol), benzyl alcohol (449 µl,
4.35 mmol) and p-TsOH (2 mg, 0.01 mmol) in benzene (8 mL) was
refluxed for 7 h. After dilution with EtOAc (20 mL), the mixture
was washed successively with sat. aq NaHCO3 (5 mL) and brine
(3 mL), dried (MgSO4) and evaporated under reduced pressure. The
residue was chromatographed (silica gel, 8 g, elution with EtOAcÐ
Synthesis 1999, No. 2, 341–354 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE
Back to the Sugars
351
IR (Nujol): n = 3418 cmÐ1.
3.56 (1 H, m), 3.40 (1 H, dd, J = 9.6, 5.8 Hz), 3.32 (1 H, dd, J = 9.9,
7.1 Hz), 3.24Ð3.21 (3 H, m).
HRMS calcd for C18H20O6 (M+) 332.1260, found 332.1245.
1H NMR (CDCl3, 300 MHz): d = 7.85Ð7.82 (3 H, m), 7.77 (1 H, s),
7.51Ð7.45 (3 H, m), 5.63 (1 H, s), 4.76 (1 H, d, J = 12.9 Hz), 4.72
(1 H, d, J = 12.9 Hz), 4.54 (1 H, dt, J = 6.2, 1.9 Hz), 4.28 (1 H, t, J
= 4.9 Hz), 4.18 (1 H, br d, J = 5.2 Hz), 3.58 (1 H, dd, J = 9.7,
5.8 Hz), 3.46 (1 H, dd, J = 9.7, 6.5 Hz), 3.07 (2 H, s), 2.15 (1 H, br
d, J = 4.7 Hz).
(+)-(1R,2S,3R,4S,5S,7R)-2,3,4-Trisbenzyloxy-7-(2-naphthyl-
methyloxymethyl)-6,8-dioxabicyclo[3.2.1]octane (42)
To a stirred solution of the triol 41 (110 mg, 0.33 mmol) in THF
(3 mL) was added NaH (60% in oil, 106 mg, 2.65 mmol) at 0¡C
and, after having ceased hydrogen gas evolution, BnBr (394 µL,
3.30 mmol) was added. After refluxing for 8 h, MeOH (28 µL,
0.69 mmol) followed by NaH (60% in oil, 28 mg, 0.69 mmol) was
added to the mixture at r.t. and the mixture was diluted with EtOAc
(20 mL). The mixture was successively washed with H2O (5 mL)
and brine (3 mL), and dried (MgSO4). After evaporation of the sol-
vent under reduced pressure, the residue was chromatographed (sil-
ica gel, 2 g, elution with EtOAcÐhexane, 1:10 v/v) to give the
tribenzyl ether 42 (196 mg, 98%) as a colorless oil: [a]D30 +14.72 (c
= 1.2, CHCl3).
1H NMR (CDCl3, 300 MHz): d = 7.84Ð7.76 (4 H, m), 7.49Ð7.44 (3
H, m), 7.36Ð7.21 (15 H, m), 5.35 (1 H, s), 4.91 (1 H, t, J = 6.6 Hz),
4.74 (1 H, d, J = 12.2 Hz), 4.68 (1 H, d, J = 12.2 Hz), 4.64Ð4.55 (4
H, m), 4.45 (1 H, d, J = 12.1 Hz), 4.37Ð4.32 (2 H, m), 3.90Ð3.87 (1
H, m), 3.82Ð3.80 (1 H, m), 3.53Ð3.48 (2 H, m), 3.39 (1 H, dd, J =
17.0, 7.4 Hz).
HRMS calcd for C18H18O5 (M+) 314.1154, found 314.1158.
(+)-(1S,2S,3S,4S,5S,7R)-2-Benzoyloxy-3,4-epoxy-7-(2-naph-
thylmethyloxymethyl)-6,8-dioxabicyclo[3.2.1]octane (39)
To a stirred mixture of the epoxy alcohol 38 (468 mg, 1.49 mmol)
and pyridine (542 µL, 6.71 mmol) in CH2Cl2 (10 mL) was added
benzoyl chloride (606 µL, 5.23 mmol) at 0¡C and the stirring was
continued for 22 h at r.t.. The mixture was diluted with EtOAc
(30 mL) and was washed successively with H2O (5 mL) and brine
(3 mL), and dried (MgSO4). After evaporation of the solvent under
reduced pressure, the residue was chromatographed (silica gel,
10 g, elution with EtOAcÐhexane, 1:30 then 1:10 v/v) to give the
benzoate 39 (582 mg, 93%) as colorless needles, mp 75Ð77¡C: [a]D27
+28.85 (c = 1.0, CHCl3).
IR (Nujol): n = 1720 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 8.00Ð7.96 (2 H, m), 7.82Ð7.67 (3
H, m), 7.64 (1 H, s), 7.56Ð7.41 (3 H, m), 7.37Ð7.30 (3 H, m), 5.71
(1 H, s), 5.41 (1 H, dd, J = 5.2, 0.8 Hz), 4.64 (2 H, s), 4.58 (1 H, td,
J = 6.6, 1.6 Hz), 4.51 (1 H, dt, J = 5.2, 1.9 Hz), 3.61 (1 H, dd, J =
9.6, 5.6 Hz), 3.44 (1 H, dd, J = 9.6, 7.1 Hz), 3.26 (1 H, dd, J = 3.2,
2.1 Hz), 3.13 (1 H, d, J = 3.8 Hz).
HRMS calcd for C32H31O6 (M+ Ð C7H7) 511.2121, found 511.2094.
(+)-(1R,2S,3R,4S,5S,7R)-2,3,4-Trisbenzyloxy-7-hydroxymeth-
yl-6,8-dioxabicyclo[3.2.1]octane (43)
To a stirred suspension of 10% Pd/C (50 mg) in EtOH (6 mL) con-
taining 1 drop of CHCl3 was added the ether 42 (302 mg,
0.50 mmol) under hydrogen at r.t. and the stirring was continued for
1.5 h at the same temperature. After filtration through a Celite pad,
the filtrate was evaporated under reduced pressure and the residue
was chromatographed (silica gel, 6 g, elution with EtOAcÐhexane,
1:3 v/v) to give the primary alcohol 43 (223 mg, 96%) as a colorless
oil: [a]D27 +32.45 (c = 1.1, CHCl3).
HRMS calcd for C29H22O6 (M+) 418.1416, found 418.1417.
(+)-(1S,2S(R),3S(R),4S,5S,7R)-2(3)-Benzoyloxy-3(2),4-dihy-
droxy-7-(2-naphthylmethyloxymethyl)-6,8-dioxabicyclo-
[3.2.1]octane (40)
To a stirred solution of the epoxybenzoate 39 (513 mg, 1.23 mmol)
in benzene (10 mL) was added BF3áEt2O (150 µL, 1.23 mmol) at r.t.
After stirring for 20 min at the same temperature, the mixture was
diluted with EtOAc (20 mL) and was washed successively with
H2O (5 mL) and brine (3 mL), and dried (MgSO4). After evapora-
tion of the solvent under reduced pressure, the residue was chro-
matographed (silica gel, 10 g, elution with EtOAcÐhexane, 1:1 v/v)
to give the diol 40 (508 mg, 95%) as an amorphous solid: [a]D27
+24.11 (c = 1.0, CHCl3).
IR (film): n = 3482 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.38Ð7.22 (15 H, m), 5.37 (1 H,
s), 5.79 (1 H, t, J = 15.4 Hz), 4.62 (1 H, d, J = 12.1 Hz), 4.60 (1 H,
d, J = 13.2 Hz), 4.56 (1 H, d, J = 13.2 Hz), 4.54 (1 H, d, J = 12.1 Hz),
4.46 (1 H, d, J = 12.2 Hz), 4.37 (1 H, d, J = 12.2 Hz), 4.24 (1 H, d,
J = 3.8 Hz), 3.88 (1 H, t, J = 4.4 Hz), 3.82Ð3.80 (1 H, m), 3.55Ð3.52
(3 H, m), 1.76 (1 H, br.t, J = 5.9 Hz).
IR (film): n = 3444, 1717 cmÐ1.
HRMS calcd for C21H23O6 (M+ Ð C7H7) 371.1497, found 371.1501.
1H NMR (CDCl3, 300 MHz): d = 8.07Ð8.04 (2 H, m), 7.84Ð7.80 (3
H, m), 7.77 (1 H, s), 7.63Ð7.58 (1 H, m), 7.49Ð7.44 (4 H, m), 5.46
(1 H, t, J = 0.7 Hz), 5.40Ð5.38 (2 H, m), 4.79Ð4.67 (3 H, m), 4.41Ð
4.34 (2 H, m), 3.88 (1 H, dt, J = 9.1, 1.4 Hz), 3.58 (1 H, dd, J = 9.6,
5.8 Hz), 3.45 (1 H, dd, J = 9.6, 7.1 Hz), 2.38 (1 H, d, J = 4.9 Hz),
2.26 (1 H, d, J = 9.1 Hz).
(Ð)-(1R,2S,3R,4S,5S,7R)-2,3,4-Trisbenzyloxy-7-iodomethyl-6,8-
dioxabicyclo[3.2.1]octane (45)
To a stirred suspension of 43 (1.99 g, 4.31 mmol) and Et3N (1.8 mL,
12.93 mmol) in CH2Cl2 (40 mL) was added MsCl (500 µL,
6.47 mmol) at 0¡C. After 1 h at the same temperature, the mixture
was diluted with EtOAc (200 mL) and was washed successively
with H2O (40 mL) and brine (20 mL), dried (MgSO4), and evapo-
rated under reduced pressure to give the crude mesylate 44 which
was used without purification.
HRMS calcd for C25H24O7 (M+) 436.1522, found 436.1515.
(+)-(1R,2S,3R,4S,5S,7R)-2,3,4-Trihydroxy-7-(2-naphthylmeth-
yloxymethyl)-6,8-dioxabicyclo[3.2.1]octane (41)
To a stirred solution of the benzoate 40 (460 mg, 1.06 mmol) in
MeOH (9 mL) was added NaOMe (285 mg, 5.30 mmol) at r.t. and
the stirring was continued for 45 min at same temperature. After
evaporation of the solvent, the residue was chromatographed (silica
gel, 9 g, elution with EtOAcÐhexane, 5:1 v/v) to give the triol 41
(287 mg, 82%) as colorless prisms, mp 184Ð186¡C: [a]D29 +7.46 (c
= 1.0, EtOH).
A solution of 44 obtained and LiI (5.76 g, 43.05 mmol) in THF
(40 mL) was then refluxed for 17 h and the mixture, diluted with
EtOAc (200 mL) and was washed successively with 10% aq
Na2S2O3 (40 mL), sat. aq NaHCO3 (40 mL), and brine (20 mL),
dried (MgSO4) and evaporated under reduced pressure. The residue
was chromatographed (silica gel, 40 g, elution with EtOAcÐhexane,
1:15 v/v) to give the iodide 45 (2.3 g, 93%) as a colorless oil: [a]D27
Ð1.57 (c = 1.1, CHCl3).
IR (Nujol): n = 3454 cmÐ1.
1H NMR (CD3OD, 300 MHz): d = 7.77Ð7.73 (4 H, m), 7.41Ð7.36
(3 H, m), 5.18 (1 H, t, J = 1.6 Hz), 4.69Ð4.58 (3 H, m), 4.06 (1 H, br
d, J = 2.7 Hz), 3.88 (1 H, t, J = 4.7 Hz), 3.82Ð3.76 (1 H, m), 3.60Ð
1H NMR (CDCl3, 300 MHz): d = 7.61Ð7.17 (15 H, m), 5.41 (1 H,
s), 4.95 (1 H, dd, J = 9.3, 5.2 Hz), 4.69 (1 H, d, J = 12.1 Hz), 4.63
Synthesis 1999, No. 2, 341–354 ISSN 0039-7881 © Thieme Stuttgart á New York

352
M. Takeuchi et al.
FEATURE ARTICLE
(1 H, d, J = 12.4 Hz), 4.59 (1 H, d, J = 12.1 Hz), 4.55 (1 H, d, J =
12.4 Hz), 4.46Ð4.42 (2 H, m), 4.32 (1 H, d, J = 12.4 Hz), 3.86 (1 H,
t, J = 4.4 Hz), 3.82Ð3.09 (1 H, m), 3.47 (1 H, s), 3.18 (1 H, dd, J =
9.5, 5.5 Hz), 3.06 (1 H, dd, J = 9.5 Hz).
MeOHÐH2O, 15:2:1 v/v) to give the L-galactose 49 (180 mg, 92%)
as an amorphous solid: [a]D29 Ð77.62 (c = 0.8, H2O) [lit. [a]D23 Ð72.2
(c = 0.70, H2O), [a]D Ð81].
HRMS calcd for C21H22IO5 (M+ÐC7H7) 481.0513, found 481.0493.
(Ð)-(1S,3R,4S,5S,7R)-7-tert-Butyldimethylsiloxymethyl-3,4-ep-
oxy-6,8-dioxabicyclo[3.2.1]octan-4-one 34 (P = TBS)
To a stirred solution of 11 (P = TBS) (1.31 g, 4.84 mmol) in THF
(30 mL) and 0.5 M NaOH (4.9 mL, 2.42 mmol) was added 30%
H2O2 (823 µL, 7.26 mmol) at 0 ¡C. After stirring for 10 min at r.t.,
the mixture was diluted with EtOAc (50 mL) and was washed suc-
cessively with H2O (10 mL) and brine (5 mL), and dried (MgSO4).
After evaporation of the solvent under reduced pressure, the residue
was chromatographed (silica gel, 20 g, elution with EtOAcÐhexane,
1:5 v/v) to give 34 (1.24 g, 90%) as a colorless oil: [a]D29 Ð5.24 (c =
1.1, CHCl3).
IR (film): n = 1738 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 5.83 (1 H, s), 4.48 (1 H, s), 3.91
(1 H, ddd, J = 7.8, 5.2, 1.2 Hz), 3.65 (1 H, dd, J = 10.2, 5.2 Hz),
3.48Ð3.42 (2 H, m), 3.32Ð3.30 (1 H, m), 0.86 (9 H, s), 0.03 (6 H, s).
(2R/S,3S,4R,5S,6S)-3,4,5-Trisbenzyloxy-6-vinyloxan-2-ol (46)
A solution of 45 (2.3 g, 4.02 mmol) in HOAc (50 mL) was stirred
with activated Zn powder (13.1 g, 201 mmol) at r.t. for 1 h. After
filtration, the filtrate was diluted EtOAc (2 × 200 mL) and was
washed successively with H2O (40 mL), sat. aq NaHCO3 (40 mL),
and brine (20 mL), dried (MgSO4) and evaporated under reduced
pressure. The residue was chromatographed (silica gel, 40 g, elution
with EtOAcÐhexane, 1:5 v/v) to give 46 (1.75 g, 98%) as a colorless
crystalline solid, mp 75Ð77¡C.
IR (Nujol): n = 3396 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.40Ð7.24 (15 H, m), 5.89 (0.34
H, ddd, J = 17.0, 10.3, 5.8 Hz), 5.87 (0.66 H, ddd, J = 17.0, 10.4,
6.0 Hz), 5.36Ð5.28 (1.66 H, m), 5.19 (0.34 H, dt, J = 10.3, 1.7 Hz),
5.17 (0.66 H, dt, J = 10.4, 1.4 Hz), 4.95Ð4.64 (6.68 H, m), 4.45 (0.66
H, br.d, J = 5.8 Hz), 4.07 (0.66 H, dd, J = 9.6, 3.6 Hz), 3.96Ð3.75 (3
H, m), 3.57 (0.34 H, dd, J = 9.6, 3.0 Hz).
HRMS calcd for C9H13O5Si (M+ÐC4H9) 229.0532, found 229.0523.
(+)-(1R,4S,5S,7R)-7-tert-Butyldimethylsiloxymethyl-6,8-dioxa-
bicyclo[3.2.1]octan-2-en-4-ol (50)
HRMS calcd for C21H23O5 (M+ Ð C7H7) 355.1546, found 355.1558.
To a stirred solution of 34 (P = TBS) (102 mg, 0.36 mmol) in MeOH
(2 mL) containing HOAc (2 µL, 0.04 mmol) was added hydrazine
hydrate (99%, 52 µL, 1.08 mmol), at 0¡C and the stirring was con-
tinued for 3 h at r.t.. The mixture was diluted with Et2O (3 mL) and
treated with sat. aq NaHCO3 (1 mL). The mixture was extracted
with EtOAc (20 mL) and the extract washed successively with H2O
(5 mL) and brine (3 mL), dried (MgSO4), and evaporated under re-
duced pressure. The residue was chromatographed (silica gel, 2 g,
elution with EtOAc-hexane, 1:8 v/v) to give 50 (60 mg, 62%) as a
pale yellow oil: [a]D30 +34.48 (c = 1.2, CHCl3).
(2R/S,3S,4R,5S,6S)-2,3,4,5-Tetrakisbenzyloxy-6-vinyloxane (47)
A solution of 46 (1.75 g, 3.93 mmol) and benzyl alcohol (2.03 mL,
19.65 mmol) in benzene (40 mL) was refluxed in the presence of p-
TsOH (7 mg, 0.04 mmol) for 23 h. The mixture, after dilution with
EtOAc (100 mL) was washed successively with sat. aq NaHCO3
(20 mL), and brine (10 mL), dried (MgSO4) and evaporated under
reduced pressure. The residue was chromatographed (silica gel,
40 g, elution with EtOAcÐhexane, 1:10 v/v) to give 47 (1.94 g,
92%) as a colorless crystalline solid, mp 74Ð76 ûC.
1H NMR (CDCl3, 300 MHz): δ = 7.41Ð7.19 (20 H, m), 5.89 (0.34 H,
ddd, J = 16.8, 10.7, 5.8 Hz), 5.84 (0.66 H, ddd, J = 17.3, 10.6, 6.0 Hz),
5.35 (0.34 H, dt, J = 16.8, 1.4 Hz), 5.26 (0.66 H, dt, J = 17.3, 1.6 Hz),
5.20 (0.34 H, dt, J = 10.7, 1.4 Hz), 5.15 (0.66 H, dt, J = 10.6, 1.6 Hz),
5.06Ð4.48 (9 H, m), 4.24 (0.66 H, br d, J = 6.0 Hz), 4.10Ð4.00 (1.32
H, m), 3.93 (0.34 H, dd, J = 9.9, 7.7 Hz), 3.84Ð3.80 (1 H, m), 3.73
(0.34 H, br d, J = 2.2 Hz), 3.54 (0.34 H, dd, J = 9.9, 3.0 Hz).
IR (film): n = 3428 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 6.22 (1 H, dd, J = 9.9, 4.7 Hz),
5.85Ð5.80 (1 H, m), 5.48 (1 H, s), 4.54 (1 H, d, J = 4.7 Hz), 3.83 (1
H, dd, J = 9.5, 4.9 Hz), 3.63Ð3.56 (2 H, m), 3.40 (1 H, dd, J =
9.5 Hz), 1.77 (1 H, br d, J = 10.2 Hz), 0.89 (9 H, s), 0.06 (6 H, s).
HRMS calcd for C9H15O4Si (M+ÐC4H9) 215.0740, found 215.0696.
HRMS calcd for C28H29O5 (M+ÐC7H7) 445.2014, found 445.2042.
(+)-(1R,5S,7R)-7-tert-Butyldimethylsiloxymethyl-6,8-dioxabi-
cyclo[3.2.1]oct-2-en-4-one (51)
(2R/S,3S,4R,5S,6S)-2,3,4,5-Tetrakisbenzyloxy-6-hydroxymeth-
yloxane (48)
To a stirred solution of 50 (26 mg, 0.10 mmol) in CH2Cl2 (4 mL)
and NaOAc (24 mg, 0.30 mmol) was added pyridinium chlorochro-
mate (PCC) (41 mg, 0.20 mmol) at r.t. in the pressure of florisil
(41 mg) the stirring was continued for 10 h. After filtration through
a Celite pad, the filtrate was evaporated under the reduced pressure
and chromatographed (silica gel, 1 g, elution with EtOAcÐhexane,
1:10 v/v) to give 51 (16mg, 62%) as a pale yellow oil: [a]D25 +266.83
(c = 1.2, CHCl3).
To a stirred solution of 47 (704 mg, 1.31 mmol) in MeOHÐCH2Cl2
(1:1 v/v, 40 mL) was introduced ozone at Ð78¡C for 10 min. After
excess ozone was removed by introduction of Ar, NaBH4 (500 mg,
13.13 mmol) was added at the mixture and the mixture was stirred
at r.t. for 20 min. After evaporation of the solvent under reduced
pressure, the residue was chromatographed (silica gel, 15 g, elution
with EtOAcÐhexane, 1:2 v/v) to give 48 (613 mg, 86%) as a color-
less crystalline solid, mp 69Ð72¡C.
IR (film): n = 1711 cmÐ1.
1H NMR (CDCl3, 300 MHz): δ = 7.32 (1 H, dd, J = 9.9, 4.7 Hz), 6.14
(1 H, dd, J = 9.9, 1.6 Hz), 5.33 (1 H, d, J = 1.6 Hz), 4.86 (1 H, d, J =
4.7 Hz), 3.92 (1 H, dd, J = 9.6, 4.9 Hz), 3.77 (1 H, dd, J = 9.6, 4.9 Hz),
3.46 (1 H, dd, J = 9.6 Hz), 0.91 (9 H, s), 0.09 (3 H, s), 0.08 (3 H, s).
IR (Nujol): n = 3394 cmÐ1.
1H NMR (CDCl3, 300 MHz): δ = 7.43Ð7.17 (20 H, m), 4.99Ð4.47
(9 H, m), 4.08Ð3.34 (6 H, m), 1.48Ð1.42 (1 H, m).
HRMS calcd for C27H29O6 (M+ÐC7H7) 449.1963, found 449.1945.
HRMS calcd for C13H22O4Si (M+) 270.1286, found 270.1279.
L-Galactose (49)
(+)-(1R,4R,5S,7R)-7-tert-Butyldimethylsiloxymethyl-6,8-dioxa-
bicyclo[3.2.1]oct-2-en-4-ol (52)
To a stirred solution of 51 (185 mg, 0.69 mmol) and CeCl3á7H2O
(306 mg, 0.83 mmol) in MeOH (5 mL) was added NaBH4 (31 mg,
0.83 mmol) at 0¡C. After 30 min at the same temperature the mix-
ture was diluted with EtOAc (20 mL) and washed successively with
A solution of 48 (590 mg, 1.09 mmol) in MeOH (12 mL) was hy-
drogenated on Pd(OH)2 (59 mg) at r.t. for 176 h. The mixture was
diluted with MeOH (20 mL) and filtered through a Celite pad to re-
move the catalyst. The filtrate was evaporated under reduced pres-
sure and chromatographed (silica gel, 12 g, elution with EtOAcÐ
Synthesis 1999, No. 2, 341–354 ISSN 0039-7881 © Thieme Stuttgart · New York

FEATURE ARTICLE
Back to the Sugars
yl-6,8-dioxabicyclo[3.2.1]octane (56)
To a stirred solution of 55 (250 mg, 0.43 mmol) in THF (5 mL) was
added TBAF (1.0 M in THF, 651 µL, 0.65 mmol) at 0¡C and was
treated as for 17 to give 56 (198 mg, 99%) as a colorless oil after
chromatography (silica gel, 5 g, elution with EtOAcÐhexane, 1:2 v/
v): [a]D26 +60.48 (c = 1.1, CHCl3).
353
H2O (5 mL) and brine (3 mL). The mixture was evaporated under
reduced pressure and chromatographed (silica gel, 4g, elution with
EtOAcÐhexane, 1:10 v/v) to give 52 (186 mg, 100%) as a colorless
oil: [a]D29 +5.31 (c = 1.1, CHCl3).
IR (film): n = 3460 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 6.13 (1 H, ddd, J = 9.9, 4.4, 0.7
Hz), 5.71 (1 H, dt, J = 9.9, 2.3 Hz), 5.47 (1 H, t, J = 2.5 Hz), 4.50 (1
H, d, J = 4.4 Hz), 4.28 (1 H, br d, J = 11.4 Hz), 3.96 (1 H, dd, J =
9.2, 5.2 Hz), 3.56 (1 H, dd, J = 9.9, 5.2 Hz), 3.41 (1 H, dd, J = 9.9,
9.2 Hz), 2.09 (1 H, br d, J = 11.4, Hz), 0.88 (9 H, s), 0.06 (6 H, s).
IR (film): n = 3466 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.61Ð7.28 (15 H, m), 5.38 (1 H,
d, J = 1.4 Hz), 4.84 (1 H, d, J = 11.9 Hz), 4.74 (2 H, s), 4.70 (2 H,
d, J = 11.9 Hz), 4.65 (1 H, d, J = 11.9 Hz), 4.36 (1 H, br d, J = 2.5
Hz), 3.81Ð3.67 (4 H, m), 3.57Ð3.44 (2 H, m), 1.75 (1 H, br t, J = 5.9
Hz).
HRMS calcd for C9H15O4Si (M+ÐC4H9) 215.0740, found 215.0734.
HRMS calcd for C21H23O6Si (M+ÐC7H7) 371.1495, found
371.1490.
(+)-(1R,4R,5S,7R)-4-Benzyloxy-7-tert-butyldimethylsiloxy-
methyl-6,8-dioxabicyclo[3.2.1]oct-2-ene (53)
To a stirred solution of 52 (186 mg, 0.68 mmol) in THF (5 mL) was
added NaH (60% in oil, 36 mg, 0.88 mmol) followed by BnBr
(114 µL, 0.95 mmol) as for 14 to give 53 (227 mg, 92%) as a color-
less oil after chromatography (silica gel, 4 g, elution with EtOAcÐ
hexane, 1:20 v/v): [a]D29 +3.94 (c = 1.1, CHCl3).
1H NMR (CDCl3, 300 MHz): d = 7.40Ð7.27 (5 H, m), 6.14 (1 H,
ddd, J = 10.0, 4.2, 1.4 Hz), 5.73 (1 H, dt, J = 10.0, 2.2 Hz), 5.52 (1
H, t, J = 2.3 Hz), 4.69 (1 H, d, J = 12.4 Hz), 4.64 (1 H, d, J =
12.4 Hz), 4.52 (1 H, d, J = 4.4 Hz), 4.23 (1 H, q, J = 2.2 Hz), 4.10
(1 H, dd, J = 9.7, 4.9 Hz), 3.58 (1 H, dd, J = 9.7, 4.9 Hz), 3.40 (1 H,
dd, J = 9.7 Hz), 0.88 (9 H, s), 0.05 (6 H, s).
(+)-(1R,2R,3S,4R,5S,7R)-2,3,4-Trisbenzyloxy-7-iodomethyl-
6,8-dioxabicyclo[3.2.1]octane (58)
To a stirred solution of 56 (198 mg, 0.43 mmol) and Et3N (179 µL,
1.29 mmol) in CH2Cl2 (5 mL) was added MsCl (50 µL, 0.65 mmol)
at 0¡C as for 19 to give the crude mesylate 57. The crude 57 without
purification was then refluxed with Lil (573 mg, 4,30 mmol) in THF
(5 mL) for 6 h and was treated as for 19 to give 58 (223 mg, 91%)
as a colorless oil after chromatography (silica gel, 4 g, elution with
EtOAcÐhexane, 1:20 v/v): [a]D29 +37.75 (c = 1.0, CHCl3).
1H NMR (CDCl3, 300 MHz): d = 7.40Ð7.27 (15 H, m), 5.45 (1 H,
s), 4.81 (1 H, d, J = 11.8 Hz), 4.78 (1 H, d, J = 12.6 Hz), 4.73 (1 H,
d, J = 12.6 Hz), 4.68 (1 H, d, J = 11.8 Hz), 4.64 (1 H, s), 4.54 (1 H,
d, J = 0.9 Hz), 3.92 (1 H, dd, J = 10.0, 4.4 Hz), 3.75Ð3.67 (3 H, m),
3.13 (1 H, dd, J = 10.0, 4.4 Hz), 3.01 (1 H, dd, J = 10.0 Hz).
HRMS calcd for C16H21O4Si (M+ÐC4H9) 305.1209, found
305.1211.
HRMS calcd for C21H22IO5 (M+ÐC7H7) 481.0471, found 481.0520.
(+)-(1R,2R,3S,4R,5S,7R)-4-Benzyloxy-7-tert-butyldimethyl-
siloxymethyl-6,8-dioxabicyclo[3.2.1]octane-2,3-diol (54)
To a stirred solution of 53 (227 mg, 0.63 mmol), NMO (110 mg,
0.95 mmol) in acetoneÐH2O (1:1 v/v, 6 mL) was added OsO4
(0.1967 M in THF, 319 µL, 0.06 mmol) at 0 ûC and was treated as
for 15 to give 54 (225 mg, 91%) as an amorphous solid after chro-
matography (silica gel, 4 g, elution with EtOAcÐhexane, 1:4 v/v):
[a]D27 +70.20 (c = 1.0, CHCl3).
(2R/S,3R,4S,5R,6S)-3,4,5-Trisbenzyloxy-6-vinyloxan-2-ol (59)
A solution of 58 (240 mg, 0.42 mmol) in HOAc (6 mL) was stirred
with activated Zn powder (1.37 g, 21.0 mmol) at r.t. for 3 h and the
mixture was treated as for 20 to give 59 (181 mg, 97%) as a color-
less oil after chromatography (silica gel, 5 g, elution with EtOAcÐ
hexane, 1:10 v/v).
IR (film): n = 3460 cmÐ1.
IR (film): n = 3452 cmÐ1.
1H NMR (CDCl3, 300 MHz): d = 7.39Ð7.16 (15 H, m), 6.02 (0.6 H,
ddd, J = 17.3, 10.7, 6.3 Hz), 5.98 (0.4 H, ddd, J = 17.3, 10.7,
6.0 Hz), 5.51 (0.6 H, dt, J = 17.3, 1.4 Hz), 5.46 (0.4 H, dt, J = 17.3,
1.4 Hz), 5.30 (0.6 H, dt, J = 10.7, 1.4 Hz), 5.26 (0.4 H, dt, J = 10.7,
1.4 Hz), 5.10 (0.4 H, d, J = 1.6 Hz), 5.06 (0.6 H, s), 4.79Ð4.35 (7 H,
m), 3.88 (0.6 H, br t, J = 2.7 Hz), 3.74 (0.4 H, t, J = 3.3 Hz), 3.64
(0.6 H, d, J = 2.7 Hz), 3.61Ð3.59 (1.2 H, m), 3.51 (0.4 H, d, J = 2.7
Hz), 3.49Ð3.47 (0.8 H, m).
1H NMR (CDCl3, 300 MHz): d = 7.39Ð7.29 (5 H, m), 5.35 (1 H, d,
J = 1.6 Hz), 4.75 (1 H, d, J = 12.3 Hz), 4.71 (1 H, d, J = 12.3 Hz),
4.48 (1 H, d, J = 2.2 Hz), 3.91Ð3.79 (3 H, m), 3.60 (1 H, dd, J = 9.9,
4.7 Hz), 3.43Ð3.35 (2 H, m), 2.51Ð2.47 (2 H, m), 0.88 (9 H, s), 0.05
(6 H, s).
HRMS calcd for C20H33O6Si (M++1) 397.2044, found 397.2089.
(+)-(1R,2R,3S,4R,5S,7R)-2,3,4-Trisbenzyloxy-7-tert-butyldi-
methylsiloxymethyl-6,8-dioxabicyclo[3.2.1]octane (55)
To a stirred solution of 54 (256 mg, 0.65 mmol) in THF (6 mL) was
added NaH (60% in oil, 129 mg, 3.25 mmol), followed by BnBr
(461 µL, 3.90 mmol) as for 16 to give 55 (335 mg, 90%) as a color-
less oil after chromatography (silica gel, 5 g, elution with EtOAcÐ
hexane, 1:20 v/v): [a]D26 +40.84 (c = 1.1, CHCl3).
1H NMR (CDCl3, 300 MHz): d = 7.39Ð7.24 (15 H, m), 5.31 (1 H,
d, J = 1.4 Hz), 4.82 (1 H, d, J = 11.9 Hz), 4.75 (2 H, s), 4.68 (1 H,
d, J = 11.9 Hz), 4.65 (2 H, s), 4.44 (1 H, d, J = 2.5 Hz), 3.79Ð3.70
(2 H, m), 3.66Ð3.61 (2 H, m), 3.53 (1 H, dd, J = 9.7, 4.5 Hz), 3.30
(1 H, dd, J = 9.7 Hz), 0.85 (9 H, s), 0.01 (6 H, s).
HRMS calcd for C21H23O5 (MÐC7H7) 355.1546, found 355.1575.
References
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Synthesis 1999, No. 2, 341–354 ISSN 0039-7881 © Thieme Stuttgart á New York

354
M. Takeuchi et al.
FEATURE ARTICLE
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Synthesis 1999, No. 2, 341–354 ISSN 0039-7881 © Thieme Stuttgart · New York