Difunctionalised oxirane systems. Stereodivergent synthesis of 1,4;2,3-dianhydro-5-O-benzyl-L-lyxitol and -L-ribitol

Article abstract of DOI:10.1016/S0957-4166(97)00136-5

A simple, efficient, stereoselective synthesis of the diastereoisomeric cis/trans pair of difunctionalized 1,2-epoxides, 1,4;2,3-dianhydro-5-O-benzyl-L-lixitol 1 and 1,4;2,3-dianhydro-5-O-benzyl-L-ribitol 2 is described. Starting from D-(+)-xylose, the synthetic approach to 1 and 2 proceeds through the common intermediate, diol 6, and an appropriate sequence of selective functionalizations.

Full text of DOI:10.1016/S0957-4166(97)00136-5

Tetrahedron: As)mmetrx. Wol 8, No. 10, pp. 1611-1621. 1997
@
1997 Elsevier Science Lid All rights reserved.
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PII: S0957-4166(97)00136-5
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Difunctionalised oxirane systems. Stereodivergent synthesis of
1,4;2,3-dianhydro-5-O-benzyl-L-lyxitol and -L-ribitol
P a o l o Crotti,* Valeria Di Bussolo, Lucilla Favero, Claudia Gozzi and M a u r o Pineschi
Dipartimento di Chimica Bioorganica. Universith di Pisa, Via Bonanno 33, 56126 Pisa, Italy
Abstract:
A simple, efficient, stereoselective synthesis of the diastereoisomeric
cis/trans pair of difunctionalized 1,2-epoxides, 1.4;2,3-dianhydro-5-O-benzyl-L-lixitol
1
and 1,4;2,3-dianhydro-5-O-benzyl-L-ribitol 2 is described. Starting from D-(+)-xylose, the
synthetic approach to 1 and 2 proceeds through the common intermediate, diol 6, and an
appropriate sequence of selective functionalizations. @ 1997 Elsevier Science Ltd
The easy accessibility of functionalized and non-functionalized chiral 1,2-epoxides by means of
outstandingly effective procedures1 has extended the use of 1,2-epoxides in organic synthesis, in view
of their ability to react with a large variety of nucleophiles.2 However, for an effective utilization
of these versatile synthetic intermediates, the regio- and stereochemical control of the nucleophilic
opening of the oxirane ring has to be adequately addressed, thus becoming one of the most qualifying
points in the chemistry of 1,2-epoxides.3 In a program aimed at verifying whether the presence of
one or two O-heterofunctionalities contemporarily present close to the oxirane ring was able to direct
the regioselectivity of the ring opening by means of chelating processes, we needed to obtain the
two diastereoisomeric 1,2-epoxides, cis 1 and trans 2.4 Epoxides 1 and 2 appeared to be particularly
interesting due to the presence of both an endocyclic (tetrahydrofuran oxygen) and an exocyclic
(OBn oxygen) O-heterofunctionality in an allylic and homoallylic relationship to the oxirane ring,
respectively. 5 Previous studies on the synthesis of oxirane systems related to epoxides 1 and 2 were
concerned with the preparation of the epoxy alcohols corresponding to L - 1 6 a and D-26b and the
corresponding O-monomethoxytrityl,6c O-tosyl and O-mesyl derivatives6a'd by synthetic procedures
different from the one now utilized. Moreover, a simple stereoselective approach to the synthesis
of these oxirane systems appeared to be lacking. Here we describe the stereoselective synthesis of
enantiomerically pure epoxides L-1 and L-2, starting from commercially available D-(+)-xylose 3.
The reaction of 3 with isobutylmercaptane afforded the dithioacetal 4, which, on treatment with
TsC1/pyridine, directly afforded the cyclic dithioacetal 6, reasonably by cyclization in the basic medium
of the monotosylate 5, the primary reaction product (Scheme 1).7 Diol 6 is the crucial compound in
the synthetic pathway to both epoxides 1 and 2, as it is possible at this point to differentiate the two
independent processes (Schemes 2 and 4). On the route to the cis epoxide 1 (Scheme 2), treatment of 6
with t-butyldimethylsilyl chloride (TBDMS-CI, 2 equiv.) in the presence of imidazole aflbrded the di-
O-TBDMS protected compound 7, which was subjected to the known HgC12/HgO in MeCN protocol8
in order to obtain the free aldehyde 8. Subsequent BH3. Me2 S reduction of 8 gave the primary alcohol
99 which was transformed into the benzyl ether 10 by means of the BnBr/NaH alkylating mixture. In
these conditions, also some amounts (5-10%, I H NMR) of the regioisomeric ether 11 (Schemes 2 and
3, see below) were formed. Several attempts and reagents were tried in order to deprotect selectively
ether 10 to alcohol 12. The best result was obtained by means of the NBS/DMSO/H20 protocol at
r.t. 10a which led to an almost 1:1 mixture of alcohol 12 and unreacted starting ether 10 with only
a very small amount of a more polar product (diol 16, TLC). II In these conditions, regioisomeric
alcohol 13 was not formed or formed at an extent less than 3% (IH NMR). Other deprotection
*
Corresponding author.
1611

1612
P. CROTTI et al.
procedures (AcOH-H20-THE HE HF-Py, TsOH, H2SiF6, TBAF/THF) l°b'c tried on 10 turned out
to be unsatisfactory due to a non-selective monodeprotection (formation of a substantial amounts of
both 12 and 13)12 and/or extensive deprotection (formation of consistent amount of diol 16). Alcohol
12 and unreacted ether 10 were easily separated by flash chromatography. While ether 10 can be
profitably recycled, alcohol 12 was treated with TsCl/pyridine to yield the tosylate 14 which was
deprotected by means of 40% aqueous HBF4 at r.t. in MeCN to give the hydroxy tosylate 15. Base-
catalyzed cyclization of 15 with t-BuOK in benzene afforded pure cis epoxide 1.
/S(i-C,~Hg)
JS(i'C4Hg)
/S(i-C4Hg)
CH
J~S(i'C4Hg)
~ H"- S(i-C4Hg)
H~ [ . _ _ OH
H""- S(/.C4H9
H - ' - ~ O H
HO
OH(H)
~
--O~HoOH (/-C4Hs)SH HO--~-H
TsCID
o7"-1--H
J ~ O H
(OH)
HCI
H - - t - - - O H
Py
HO
H
H
H
/
3
CH2OH
CH2OTs
4
5
S
c
h
e
m
e
l.
CH2OH
""S(kCaHd
BDIMS'Cl
H O oTC
')
CliO
Et::O
'
'
H
H
I
=
H
. - !
?.H
TSDMSO
HO
H
TBDMSO
H
TBDMSO
H
9
6
7
8
NaH/BnBr
]
CH2OBn
CH2OBn
CDH2MOSBn
NBS
DMSO/H20
.
~
D
M
S
+ 1 1
~?~O_(~H~CH2O.B~HBF4
DMS TsCI
Py
N
~
~
-r--l-1
i
t
H6
4
H
"
,
,
H
H
•
TBDMSO
TsO
H
TsO
H
12
,"
10
15
14
l
c.:,oB.\
HBF4/H20
-BuOK
bl2OBn
~
BoMs61 s ~ H
/
I
p ,
CH~OB.
NO
H
16
TsCVPy
'I
I
H
CH2OBn
~
CH2OBn
HO
H
TsO
v
H
17
v 3614 cm 1
1 5
3462 cm 1
t - B u O K /
/
1
S
c
h
e
m
e
2.
The formation of some amounts of ether 11 in the benzylation reaction of alcohol 9 by the NaH/BnBr
protocol (see above) prompted us to examine more closely the process involved in its formation.
When alcohol 9 was put in contact with Nail in THF for 18 h at r.t., a 4:6 equilibrating mixture of
starting alcohol 9 and regioisomeric alcohol 18 was obtained (Scheme 3), from which pure alcohol
18 was separated by flash chromatography. While the benzylation of 18 by means of the NaH/BnBr
protocol afforded an unseparable mixture (75:25) of ethers 10 and 11, the benzylation of 18 by the
Bu4NI/BnBr/NaH procedure13 at r.t. afforded only ether 11. All this reasonably indicated that the
formation of ethers 10 and 11 from both alcohols 9 and 18 (Schemes 2 and 3) primarily derives from

Difunctionalised oxirane systems
1613
CH20H
S Nail
CH2OTBDMS
CH2OTBDM S
CH2OTBDMS
H
"
~
D
M
H ~ . ~
BnBr-Bu4M. ~H~o~OB
TBAF
~
._Z
.L H
"THF
"
.-!
J, I~
Nail
] ~ T HI
~
'
TBDMSO
H
TBDMSO
H
TBDMSO
H
HO
H
18
11
19
TsCI/Py
CH2OTBDMS
10
+
11
BnO.
H
CH2OH
0
I-BuOK
benzene
~
" HBF~rH2OMecN
O
TsO
21
H "'
TsO
H
22
20
S
c h e m e 3
a 1,5-migration of the silyl group between the two cis O-functionalities of the starting alcohols 9 and
18 under the strongly alkaline reaction conditions (NaH/BnBr protocol). 14 Only when, in the case
of 18, less drastic alkylating reaction conditions (Bu4NI/BnBr/NaH) were used 13 was the migration
process prevented. Besides being interesting from a speculative point of view, the obtainment of ether
11 turned out to be also synthetically useful as it provided a simple route to an interesting dioxabicyclo
compound. Monodeprotection of ether 11 with TBAF in THF at - 10°C afforded alcohol 19 which was
transformed into tosylate 20. Deprotection of 20 with aqueous HBF4 in MeCN afforded the hydroxy
tosylate 21 which was cyclized under basic conditions to the dioxabicyclo compound 22. Compound
22 is one of the few examples of this class of bicyclo compounds so far described. 15
The synthesis of the trans epoxide 2 starts from the common intermediate, diol 6 (Scheme 4).
Due to the consistently different steric crowding around the two secondary hydroxyl functionalities,
treatment of 6 with TBDMS-CI (1 equiv.) exclusively afforded alcohol 23, which was transformed
into the corresponding tosylate 24. Deprotection of the carbonyl functionality of 24 with HgC12/HgO
afforded the aldehyde 25 which was reduced to the primary alcohol 26 by BH3.Me2S. Benzylation
of 26 by the BnBr/NaH alkylating protocol afforded the benzyl ether 27, which was deprotected to
the hydroxy tosylate 17 by treatment with aqueous HBF4 in MeCN. Base-catalyzed cyclization of 17
with t-BuOK yielded the desired trans epoxide 2 (Scheme 4).
C1~$(kc41'~
"~S{/.C4H9)
C~I"s(/'c'tHg)
~S(/:-C4Hg) TsCl
C"~S(':'C'Hg)
Clio
I
imidazole
~
J
~ H
Py
HgO
TBDMSO
H~
~
"
r e t ) . s 6
'
'
H
'
'
.
TBDMSO
H
H
2 5
6
23
24
BH~ EtzO
CH2OH
CH2OBn
CH2OB.
CHzOen
jlH-"O ~OT~
HBF4
,,1 H20
H ~ O ~OT~
BnBr
~BuOK
d
~
H
H
~"NaH
i
i
H
TBDMSO
H
TBDMSO
17
27 TsC113
Py
2 6
S
c h e m e 4.
The relative structure and configuration of the two hydroxy tosylates 15 and 17 (Scheme 2) are
unequivocally demonstrated on the basis of their method of preparation and confirmed by their I H
NMR spectra, with appropriate double resonance experiments, and also by examination of their IR
spectra in dilute CC!4 solution (OH stretching band): while hydroxy tosylate 17 showed the presence
of only one band at 3614 cm -1 attributable to a free OH group, the regioisomer 15 showed only
the presence of a characteristic O H . . . O interaction (3462 cm -1) which is possible only when a

1614
P. CROTTI et al.
1,3-cis relationship is present in a five-membered substituted ring between the interacting groups,3a
such as the hydroxyl and benzyloxy groups in 15, thus confirming the structure given for 15 and
17. Moreover, hydroxy tosylates 15 and 17 can be obtained as a 57:43 mixture by reaction of the
diol 16 with TsCl/pyridine (1 equiv.), thus confirming their regioisomeric structure. The structures of
hydroxy tosylates 15 and 17 unequivocally define the structures of the epoxides cis 1 and trans 2,
simply formed by their respective base-catalyzed cyclization.
E x p e r i m e n t a l
Melting points were determined on a Kofler apparatus and are uncorrected. 1H and 13C NMR spectra
were determined with a Bruker AC-200 spectrometer on CDCI3 solutions using tetramethylsilane as
the internal standard. Routine IR spectra were taken on paraffin oil mulls while spectra required for
the determination of OH stretching bands (compounds 15 and 17) were taken in dried CC14 with a
Mattson 3000 FTIR spectrophotometer: the concentration of the solution was 5× 10 .3 M, or lower.
Optical rotations were measured with a Perkin-Elmer 241 digital polarimeter with a 1 dm cell. MS
spectra of compounds 1 and 2 were recorded on a Hewlett-Packard 5988A spectrometer, All reactions
were followed by TLC on Alugram SIL G/UV254 silica gel sheets (Macherey-Nagel) with detection
by UV or with 0.5% phosphomolybdic acid solution in 95% EtOH. Silica gel 60 (Macherey-Nagel
230--400 mesh) was used for flash chromatography.
Diisobutyl D-x)'lose-dithioacetal 4
Following a previously described procedure,7 isobutyl mercaptane (30 ml, 25.0 g, 0.278 tool) was
added dropwise to D-(+)-xylose (3) (20.0 g, 0.133 mol) at 0°C under stirring. 36% Aqueous HCI
(26.0 ml) was added at the same temperature in one portion, and the resulting rection mixture was
vigorously stirred for 30 rain at r.t. Dilution with CH2C12 (200 ml) and evaporation of the washed
(saturated aqueous NaHCO3 and water) organic solution afforded a liquid crude reaction product (40.0
g) consisting of practically pure 4 which was utilized in the next step without any further purification.
An analytical sample (0.20 g) was filtered by flash chromatography eluting with a 9:0.5:0.5 mixture
of AcOEt, hexane, and MeOH to give pure 4 (0.18 g), as a liquid: [CX]D20=+71.7 (c 1.63, CHC13)
[lit. 16 [0qD20=+14.7 (c 3.34, MeOH)]; IH NMR 6 4.28-4.44 (m, 1H), 3.76-4.02 (m, 6H), 3.49-3.70
(m, 3H), 2.37-2.62 (m, 4H), 1.68-1.87 (m, 2H), 0.94 (d, 12H, J=6.4 Hz). 13C NMR ~i 74.36, 74.21,
71.21, 64.68, 56.90, 40.87, 39.27, 29.02, 22.84, 22.72. Anal. Calcd for C13H2804S2: C, 49.97; H,
9.03 Found: C, 49.67; H, 8.81.
Diisobuo,l 2,5-anhydro-D-x),lofuranose dithioacetal 6
A solution of TsCI (27.3 g, 0.144 tool) in anhydrous pyridine (150 ml) was added dropwise at
-
15°C to a stirred solution of 4 (40.0 g, 0.132 mol) in anhydrous pyridine (200 ml), and the resulting
reaction mixture was stirred at the same temperature for 1.5 h, then for two days at r.t. Dilution with
CHCI3 and ice-cold water, and evaporation at a temperature not higher than 35°C of the washed
(saturated aqueous NaHCO3, and water) organic solvent afforded a crude semisolid residue (38.2 g)
which was recrystallized from hexane-CHCI3 to give pure 6 (33.0 g, 85% yield), as a solid, m.p.
93-94°C: [CX]D20=+6.22 (c 0.74, CHC13) [lit.17 m.p. 94°C [0I]D21=+I 1.5 (c 0.62, CHC13)]; IH NMR
6 4.09-4.28 (m, 3H), 3.11 (dd, 1H, J=9.1 and 3.1 Hz), 3.87-3.92 (m, 1H), 3.65 (dd, 1H, J---9.8 and
1.0 Hz), 3.16 (d, IH, J=4.6 Hz), 3.10 (d, 1H, J=3.6 Hz), 2.43-2.68 (m, 4H), 1.67-1.84 (m, 2H), 0.93
(d, 12H J=6.7 Hz). 13C NMR 8 83.07, 78.42, 77.70, 74.31, 52.11, 39.87, 39.37, 28.98, 28.90, 22.78,
22.64. Anal. Calcd for C13H260382: C, 53.02; H, 8.90. Found: C, 53.32; H, 8.44.
Diisobu~'l 2,5-anhydro-3, 4-di-(O-t-butyldimethylsilyl)-D-xy'lofuranose dithioacetal 7
A solution of 6 (6.0 g, 20.4 mmol) in anhydrous DMF (40.0 ml) containing imidazole (6.66 g, 98.0
mmol) was treated at 0°C under stirring with t-butyldimethylsilyl chloride (TBDMS-C1) (7.95 g, 53.0
mmol) and the reaction mixture was stirred for 30 rain at the same temperature, and then for 3 days
at r.t. Dilution with petroleum ether and evaporation of the washed (saturated aqueous NaHCO3 and

Difunctionalised oxirane systems
1615
brine) afforded a crude oily product (10.5 g) which was filtered through a short silica gel column.
Elution with a 9:1 mixture of hexane and AcOEt afforded pure 7 (10.1 g, 95% yield), as a liquid:
[CX]D20=-32.07 (c 3.48, CHC13); 1H NMR 6 4.03-4.14 (m, 3H), 3.98-3.99 (m, 2H), 3.66 (d, IH,
J=8.8 Hz), 2.42-2.67 (m, 4H), 1.66-1.93 (m, 2H), 0.98 (d, 6H, J=3.8 Hz), 0.95 (d, 6H, J=4.0 Hz),
0.85 (s, 9H), 0.84 (s, 9H), 0.12 (s, 3H), 0.10 (s, 3H), 0.04 (s, 3H), 0.02 (s, 3H). 13C NMR ~5 83.19,
78.60, 78.34, 75.60, 51.89, 40.19, 38.16, 29.73, 26.38, 23.17, 23.09, 22.97, 18.81, 18.64, 18.55, -2.26,
-3.45, -4.05. Anal. Calcd for C25H5403S2Si2: C, 57.41; H, 10.41. Found: C, 57.66; H, 10.59.
2,5-Anhydro-3,4-di-(O-t-but),ldimethylsilyl)-D-.~,lofuranose
8
Following a previously described procedure,8 a solution of 7 (10.7 g, 20.5 mmol) in MeCN (200
ml) was added dropwise at r.t to a stirred suspension of HgCI2 (12.3 g, 45.3 mmol) and HgO (4.9 g,
22.6 mmol) in a 4:1 MeCN:H20 mixture (200 ml). The reaction mixture was stirred for 1 h at the same
temperature, then filtered on Celite, washing the residue with a 1:1 mixture of hexane and CH2C12
(300 ml). Evaporation of the washed (5 M aqueous MeCOONH4, saturated aqueous NaHCO3 and
brine) organic solution afforded a crude reaction product (6.64 g, 90% yield) consisting of aldehyde
8 practically pure which was rapidly utilized in the next step without any further purification. An
analytical sample (0.15 g) was purified by flash chromatography: elution with a 8:2:0.5 mixture of
hexane, AcOEt and NEt3 afforded pure 8 (0.110 g), as a liquid: [~X]D20=+53.03 (c 1.41, CHCI3); IH
NMR 6 9.62 (d, 1H, J = l . 6 Hz), 4.28-4.33 (m, 2H), 4.22 (dd, 1H, J=8.9 and 2.9 Hz), 4.06 (d, IH,
J=3.0 Hz), 3.82 (d, 1H, J=8.9 Hz), 0.85 (s, 9H), 0.80 (s, 9H), 0.06 (s, 3H), 0.05 (s, 6H), 0.04 (s, 3H).
13C NMR ~i 203.81, 86.31, 81.05, 78.62, 76.18, 26.31, 26.18, 18.48, -4.03, -4.60. Anal. Calcd for
C17H3604Si2: C, 56.61; H, 10.06. Found: C, 56.26; H, 10.37.
1,4-Anhydro-2,3-di-(O-t-bu~,ldimethylsilyl)-L-©'litol
9
10 M BH3 .Me2S (5.3 ml) was added dropwise at 0°C to a stirred solution of aldehyde 8 (7.30 g,
20.4 mmol) in anhydrous ether (400 ml) and stirring was prolonged for 2 h at r.t. After cooling to 0°C,
MeOH (35 ml) was added and the reaction mixture was stirred at r.t. overnight. Evaporation of the
solvent afforded an oily reaction product (6.6 g, 93% yield) consisting of practically pure alcohol 9
which was utilized in the next step without any further purification. An analytical sample (0.10 g) was
purified by preparative TLC (an 8:2 mixture of hexane and AcOEt was used as the eluant): extraction
of the most intense band afforded pure alcohol 9 (0.075 g), as a liquid: [CX]D20=--9.8 (c 1.10, CHCI3);
IH NMR 6 3.95-4.09 (m, 4H), 3.68-3.83 (m, 2H), 3.56-3.63 (m 1H), 0.85 (s, 9H), 0.83 (s, 9H), 0.07
(s, 3H), 0.05 (s, 3H), 0.03 (s, 3H), 0.02 (s, 3H). 13C NMR 6 81.10, 79.78, 79,16, 74.16, 62.90, 26.34,
18.53, -3.97, -4.43. Anal. Calcd for C17H3804Si2: C, 56.30; H, 10.56. Found: C, 56.65; H, 10.72.
1,4-Anhydro-2,3-di-(O-t-butyldimethylsilyl)-5-O-benzyl-L-x~,lito110
A solution of alcohol 9 (6.60 g, 18.2 mmol) in anhydrous THF (20 ml) was added to a stirred
suspension of Nail (2.18 g of a 60% dispersion in mineral oil, 54.4 mmol) in anhydrous THF (50
ml) containing benzyl bromide (2.15 ml, 18.2 retool) and the resulting reaction mixture was stirred
at 50°C for 18 h. After cooling, ether (120 ml) and water (10 ml) were carefully added in order to
destroy the excess of hydride. Evaporation of the washed (brine) organic solution afforded a crude
liquid product (7.9 g) mostly consisting of benzyl ether 10 which was filtered through a short silica
gel column. Elution with a 9:1 mixture of petroleum ether and ether afforded pure 10 (7.31 g, 89%
yield), as a liquid: [~X]D20=+3.94 (c 1.14, CHCI3); XH NMR ~i 7.26-7.38 (m, 5H), 4.58 and 4.52
(ABdd, 2H, J=10.9 Hz), 4.18--4.23 (m, 1H), 4.04-4.10 (m, 2H), 3.98 (dd, IH, J=3.0 and 1.0 Hz),
3.61-3.68 (m, 3H), 0.88 (s, 18H), 0.08 (s, 3H), 0.07 (s, 3H), 0.06 (s, 3H), 0.05 (s, 3H). 13C NMR 6
138.87, 128.97, 128.60, 128.22, 80.30, 78.91, 78.64, 74.67, 74.23, 69.72, 26.64, 26.37, 18.65, 18.56,
-3.91, -4.01, -4.46. Anal. Calcd for C24H4404Si2: C, 63.66; H, 9.79. Found: C, 63.49; H, 9.64.
In some cases, compound 10 turned out to be inquinated by some amounts of regioisomeric
compound 11 (5-10%) (Schemes 2 and 3). 10 and 11 could not be separated due to unsurmontable
chromatographic separation problems and their mixture was directly utilized in the next step.

1616
P. CROTTI et al.
1,4-Anhydro-3-(O-t-bu~ldimethylsilyl)-5-O-benzyl-L-x3'lito112
A solution of ether 10 (0.60 g, 1.33 mmol) in a 95:5 DMSO-H20 mixture (6 ml) was treated with N-
bromosuccinimide (NBS) (0.26 g, 1.46 mmol) and the reaction mixture was stirred in the dark for 12 h
at r.t. Dilution with ether and evaporation of the washed (10% aqueous Na2S203 and brine) afforded a
crude product (0.385 g) which was subjected to flash chromatography (an 8:2 hexane/AcOEt was used
as the eluant) to give starting ether 10 (0.112 g) and alcohol 12 (0.12 g), as a liquid: [CX]D2°=+I2.07
(c 0.78, CHC13); IH NMR ~ 7.25-7.34 (m, 5H), 4.58 and 4.50 (ABdd 2H, J=9.5 Hz), 4.21-4.29 (m,
IH), 4.09--4.19 (m, 3H), 3.68-3.72 (m, 1H), 3.59-3.63 (m, 2H), 0.86 (s, 9H), 0.08 (s, 3H), 0.04 (s,
3H). 13C NMR /5 138.72, 128.96, 128.53, 128.24, 80.39, 78.59, 78.26, 74.12, 74.00, 69.53, 26.30,
18.61, -4.10, -4.60. Anal. Calcd for C18H3004Si: C, 63.87; H, 8.93. Found: C, 64.12; H, 8.67.
Reaction of ether 10 with TBAF/THF
A solution of ether 10 (2.0 g, 4.42 mmol) in anhydrous THF (140 ml) was treated at - 3 5 ° C under
nitrogen with a 1 M TBAF solution in THF (4.4 ml), added over 40 min, and the resulting reaction
mixture was stirred for 1 h at the same temperature, then left to warm to - 1 0 ° C (1 h) and stirred for
an additional hour at this temperature. The reaction was quenched at - 1 0 ° C with water (50 ml) and
ether (50 ml). Evaporation of the washed (saturated aqueous NaHCO3 and brine) organic solution
afforded a crude reaction product (1.40 g) consisting of a 75:25 mixture of ethers 12 and 13 which
was subjected to flash chromatography. Elution with a 7:3 mixture of hexane and AcOEt afforded pure
12 (0.96 g, 62% yield) and 1,4-anhydro-2-(O-t-butyldimethylsilyl)-5-O-benzyl-L-xylitol 13 (0.30 g,
20% yield), as a liquid: [Or]D20=-- 13.62 (c 0.71, CHC13); IH NMR 6 7.30-7.35 (m, 5H), 4.64 and
4.55 (ABdd, 2H, J=12.0 Hz), 4.15-4.24 (m, 2H), 4.05-4.14 (m, 2H), 3.85-3.94 (m, 2H), 3.59-3.69
(m, IH), 3.50--3.56 (m, 1H), 0.87 (s, 9H), 0.07 (s, 6H). 13C NMR 6 137.97, 129.22, 128.66, 128.54,
79.95, 79.00, 78.92, 75.11, 74.78, 69.81, 26.40, 18.64, -4.10, -4.20. Anal. Calcd for C18H3004Si:
C, 63.87; H, 8.93. Found: C, 63.61; H, 9.19. Compound 13 can be utilized in the synthesis of the
trans epoxide 2 (see below and Scheme 4).
Following standard described procedures, l°b,c other deprotection procedures (AcOH-H20-THE
HE HF-Py, TsOH, H2SiF6, TBAF/THF) were tried on ether 10, affording unsatisfactory results.
1,4-Anhydro-2-O-tosyl-3-(O-t-bu~ldimethylsilyl)-5-O-benzyl-L-xylito114
A solution of alcohol 12 (1.60 g, 4.80 mmol) in anhydrous pyridine (15 ml) was treated at 0°C
with TsCI (1.82 g, 9.60 mmol) and the reaction mixture was stirred for 3 days at r.t. The usual work-
up afforded a crude oily residue (2.30 g) mostly consisting of tosylate 14 which was filtered through
a short silica gel column. Elution with an 8:2 mixture of hexane and AcOEt afforded pure 14 (2.12
g, 90% yield) as a solid m.p. 63-64°C: [CX]D20=+10.65 (c 0.77, CHCI3); IH NMR 6 7.75-7.81 (m,
2H), 7.26-7.36 (m, 7H), 4.63-4.72 (m, 1H), 4.52 and 4.50 (ABdd, 2H, J=12.2 Hz), 4.29 (m, IH),
4.04-4.19 (m, 2H), 3.78 (d, 1H, J=10.7 Hz), 3.56-3.59 (m, 2H), 2.44 (s, 3H), 0.82 (s, 9H), 0.02 (s,
6H). 13C NMR 8 145.88, 138.64, 134.13, 130.67, 129.01, 128.48, 128.30, 85.6, 80.42, 76.08, 74.14,
71.29, 68.81, 26.23, 22.32, 18.54, -4.32, -4.77. Anal. Calcd for C25H3606SSi: C, 60.94; H, 7.36.
Found: C, 60.76; H, 7.70.
1,4-Anhydro-2-O-tosyl-5-O-benzyl-L-xylito115
A solution of the tosylate 14 (2.0 g, 4.06 mmol) in MeCN (16 ml) was treated with a 48% aqueous
HBF4 solution (1.0 mi) and the reaction mixture was stirred for 2 h at r.t. Dilution with ether and
evaporation of the washed (saturated aqueous NaHCO3 and water) ether solution afforded a crude
reaction product (1.52 g) consisting of 15 practically pure which was filtered through a short silica gel
column. Elution with a 1:1 mixture of hexane:AcOEt afforded pure hydroxy tosylate 15 (1.30 g, 85%
yield), as a liquid: [et]D2°=-17.52 (c 1.01, CHCI3); IR (CCI4) 3462 cm -1 (1,3 OH-..O); IH NMR
6 7.78 (d, 2H, J=8.3 Hz), 7.25-7.36 (m, 7H), 4.79-4.82 (m, 1H), 4.58 and 4.52 (ABdd, 2H, J=l 1.7
Hz), 4.34 (m, 1H), 4.20 (dd, IH, J=10.8 and 4.6 Hz), 4.08 (q, IH, J=3.8 Hz), 3.77-3.84 (m, 4H), 2.44

Difunctionalised oxirane systems
1617
(s, 3H); 13C NMR 8 145.91, 137.72, 133.88, 130.70, 129.22, 128.72, 128.49, 85.94, 79.11, 77.12,
74.70, 71.52, 69.27, 22.33. Anal. Calcd for C19H2206S: C, 60.30; H, 5.86. Found: C, 60.11; H, 5.48.
1,4;2, 3-Dianhydro-5-O-benzyl-L-lyxitol 1
Hydroxy tosylate 15 (0.535 g, 1.41 mmol) was dissolved in anhydrous benzene (40 ml) and treated
under stirring with two portions (0.213 g × 2) of t-BuOK over 2 h. Evaporation of the filtered
organic solvent afforded a crude product (0.293 g) consisting of epoxide 1 which was purified by flash
chromatography. Elution with a 7:3 mixture of hexane and AcOEt and few drops of NEt3 afforded
pure 1 (0.28 g, 96% yield), as a liquid: [~X]D20=+66.09 (c 1.28, CHCI3); IH NMR 8 7.24-7.35 (m,
5H), 4.59 and 4.56 (ABdd, 2H, J=l 1.9 Hz) 4.04 (d, IH, J=10.6 Hz), 4.00 (t, IH, J=6.2 Hz), 3.76 (dd,
2H, J=5.4 and 3.3 Hz), 3.69 (d, 1H, J=10.2 Hz), 3.65 (d, 2H, J=6.2 Hz). 13C NMR 8 138.51,130.43,
129.02, 128.38, 128.39, 76.91, 74.23, 70.81, 69.22, 68.34, 57.22, 56.64. MS (m/e) 206 (M+), 158,
145, 117, 91, 85, 69, 65. Anal. Calcd for C12HI403: C, 69.89; H, 6.84. Found: C, 70.10; H, 6.52.
Equilibrating mixture of alcohols 9 and 18
A solution of alcohol 9 (0.90 g, 2.48 mmol) in anhydrous THF (20 ml) was treated under stirring
at 0°C with Nail (0.40 g of a 60% dispersion in mineral oil, 10.0 mmol) and the reaction mixture was
stirred for 90 min at r.t. Ether and water were carefully added in order to destroy the excess of hydride.
Evaporation of the washed (brine) organic solution afforded a crude liquid product (1.0 g) consisting
of a 40:60 mixture (1H NMR) of alcohols 9 and 18 which was subjected to flash chromatography:
elution with an 8:2 mixture of hexane and AcOEt afforded alcohol 9 (0.25 g, 28% yield) and 1,4-
anhydro-2,5-di-(O-t-butyldimethylsilyl)-L-xylitol 18 (0.432 g, 48% yield), as a solid m.p. 35-37°C:
IH NMR 8 4.30 (d, 1H, J=3.6 Hz), 4.06-4.17 (m, 5H), 4.00 (t, 1H, J=3.2 Hz), 3.65 (d, 1H, J=8.0
Hz), 0.90 (s, 9H), 0.88 (s, 9H), 0.11 (s, 6H), 0.09 (s, 3H), 0.08 (s, 3H). 13C NMR 8 80.45, 79.21,
79.02, 75.01,63.73, 26.40, 18.77, 18.68, -4.10, -4.22, -4.83, -4.98. Anal. Calcd for CI7H3804Si2:
C, 56.30; H, 10.56. Found: C, 56.18; H, 10.71.
Prolonged reaction times (two days) led to a complex reaction mixture (extensive decomposition).
1, 4-Anhydro-3-O-benzyl-2,5-di-(O-t-bu~ldimethylsilyl)-L-xylito111
Following a previously described procedure, 13 a solution of alcohol 18 (0.30 g, 0.83 mmol) in
anhydrous THF (7 ml) was treated under nitrogen in succession with Nail (0.040 g of a 60% dispersion
in mineral oil, 1.0 mmol), tetrabutylammonium iodide (0.036 g, 0.10 mmol) and benzyi bromide (0.12
ml, 1.0 mmoi) and the reaction mixture was stirred 16 h at r.t. Dilution with ether, and extraction of
the washed (brine) organic solution afforded a crude product (0.565 g) which was filtered through a
short silica gel column. Elution with a 95:5 mixture of petroleum ether and ether afforded pure 11
(0.24 g), as a liquid: IH NMR 8 7.37-7.42 (m, 5H), 4.68 (s, 2H), 4.32--4.35 (m, IH), 4.11-4.18 (m,
2H), 3.85-3.93 (m, 3H), 3.68 (dd, IH, J=9.1 and 1.7 Hz), 0.97 (s, 9H), 0.92 (s, 9H), 0.13 (s, 6H), 0.08
(s, 3H), 0.06 (s, 3H). 13C NMR 8 138.97, 129.07, 128.38, 128.23, 84.79, 81.48, 76.40, 74.97, 73.05,
61.75, 26.68, 26.42, 19.42, 19.05, 18.67, -4.11, -4.60. Anal. Calcd for C24H4404Si2: C, 63.66; H,
9.79. Found: C, 63.54; H, 10.05.
1,4-Anhydro-3-O-benzyl-5-(O-t-butyldimethylsilyl)-L-xylito119
A solution of ether 11 (0.24 g, 0.53 mmoi) in anhydrous THF (21 ml) was treated at - 4 0 ° C under
stirring with a 1 M TBAF solution in THF (0.53 mi). The reaction mixture was slowly warmed to
- 1 0 ° C and stirred at this temperature for 3 h. Dilution with ether and evaporation of the washed
(saturated aqueous NaHCO3 and brine) organic solution afforded a crude product (0.15 g) which was
subjected to preparative TLC (an 8:2 mixture of petroleum ether and AcOEt was used as the eluant).
Extraction of the most intense band afforded pure 19 (0.13 g), as a liquid: I H NMR 8 7.32-7.36 (m,
5H), 4.63-4.65 (m, 2H), 4.34--4.38 (m, 1H), 4.09-4.17 (m, 2H), 3.73-3.93 (m, 5H), 0.92 (s, 9H), 0.09
(s, 6H). 13C NMR 139.01, 129.08, 128.41, 128.20, 84.56, 81.67, 75.90, 74.26, 73.10, 61.73, 26.61,
25.52, 18.98, 18.64, -4.71. Anal. Calcd for C18H3oO4Si: C, 63.87; H, 8.93. Found: C, 64.02; H, 8.81.

1618
P. CROTTI et al.
1,4-Anhydro-2-O-tosyl-3-O-benzyl-5-(O-t-butyldimethylsilyl)-L-xylito120
Following standard procedures, the treatment of a solution of alcohol 19 (0.13 g, 0.39 mmol) in
anhydrous pyridine (1.5 ml) with TsCI (0.148 g, 0.78 mmol) for two days at r.t. afforded a crude
product (0.173 g) which was subjected to preparative TLC (a 7:3 mixture of petroleum ether and
AcOEt was used as the eluant). Extraction of the most intense band afforded pure tosylate 20 (0.12
g), as a liquid: IH NMR ~ 7.73 (d, 2H, J=8.0 Hz), 7.20-7.36 (m, 7H), 4.93-4.95 (m, 1H), 4.53 and
4.47 (ABdd, 2H, J=l 1.9 Hz), 3.93---4.13 (m, 3H), 3.81-3.69 (m, 3H), 2.42 (s, 3H), 0.84 (s, 9H), 0.00
(s, 6H). 13C NMR 6 145.85, 138.11, 134.16, 130.67, 129.07, 128.47, 128.23, 83.56, 82.03, 81.51,
72.99, 71.58, 61.44, 26.54, 22.34, 18.90, -4.74. Anal. Calcd for C25H3606SSi: C, 60.94; H, 7.36.
Found: C, 60.66; H, 7.24.
1, 4-Anhydro-2-O-tosyl-3-O-benzyl-L-xylito121
A stirred solution of ether 20 (0.12 g, 0.28 mmol) in MeCN (3 ml) was treated with 48% aqueous
HBF4 (0.18 ml) for 2 h at r.t. Usual workup afforded a crude product (0.10 g) which was subjected to
semipreparative TLC (a 7:3 mixture of petroleum ether and AcOEt was used as the eluant). Extraction
of the most intense band afforded pure hydroxy tosylate 21, as a solid m.p. 77-78°C; [(X]D20=+47.88
(c 0.93, CHCI3); 1H NMR ~ 7.79 (d, 2H, J=8.2 Hz), 7.21-7.39 (m, 7H), 4.94-5.01 (m, 1H), 4.60
and 4.44 (ABdd, 2H, J=12.1 Hz), 4.02-4.27 (m, 4H), 3.69-3.82 (m, 3H), 2.46 (s, 3H). 13C NMR
146.11, 137.44, 134.01, 130.78, 129.35, 128.97, 128.50, 83.38, 83.42, 80.65, 72.98, 71.37, 61.88,
22.38. Anal. Calcd for C19H2206S: C, 60.30; H, 5.86 Found: C, 60.46; H, 6.11.
(1 S, 4 S )- 7-Benzylox). ,-2, 5- dioxabicyclo[2.2.1 ]heptan e 22
Treatment of a benzene solution (3.0 ml) of hydroxy tosylate 21 (0.122 g, 0.32 mmol) with t-BuOK
(0.036 g × 2) as usual, afforded a reaction product (0.065 g, 92% yield) consisting of practically pure
22 which was subjected to semipreparative TLC (an 8:2 mixture of petroleum ether and AcOEt was
used as the eluant). Extraction of the most intense band afforded pure 22 (0.050 g), as a solid, m.p.
53-54°C: [Ot]D20=--48.14 (c 1.43, CHCI3): IH NMR 8 7.22-7.28 (m, 5H), 4.59 and 4.50 (ABdd,
2H, J = l l . 8 Hz), 4.20 (s, IH), 3.97-4.12 (m, 3H), 3.90 (d, 1H, J=8.4 Hz), 3.83 (s, IH). J3C NMR
138.12, 129.17, 128.68, 128.50, 80.35, 76.55, 76.49, 74.47, 73.51,72.85. Anal. Calcd for C12H1403:
C, 69.89; H, 6.84. Found: C, 69.65; H, 7.14.
Diisobutyl-2,5-anhydro-4-(O-t-butyldimethylsilyl)-D-xylofuranose dithioaceta123
A solution of 6 (6.0 g, 20.4 mmol) in anhydrous DMF (40 ml) containing imidazole (3.33 g, 48.9
mmol) was treated at 0°C with TBDMS-C1 (3.21 g, 21.4 mmol) and the reaction mixture was stirred
for 30 rain at the same temperature, and then for 3 days at r.t. The usual work-up afforded a crude
product (7.7 g) which was filtered through a short silica gel column. Elution with an 8:2 mixture of
petroleum ether and AcOEt afforded pure 23 (6.88 g, 82% yield), as a liquid: [~X]D20=-6.16 (c 1.25,
CHCI3); IH NMR 8 4.05-4.25 (m, 4H), 3.96 (d, IH, J=8.8 Hz), 3.67 (d, 1H, J=8.9 Hz), 2.59-2.72
(m, 4H), 1.79-1.89 (m, 2H), 1.03 (s, 6H), 0.99 (s, 6H), 0.88 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H). 13C
NMR 8 83.30, 79.24, 78.42, 75.31, 52.46, 40.17, 39.47, 29.22, 29.10, 26.39, 22.91, 22.80, 18.64,
-4.15. Anal. Calcd for C19H4oO3S2Si: C, 55.83; H, 9.86. Found: C, 56.13; H, 9,61.
Diisobutyl-2,5-anhydro-3-O-tosyl-4-(O-t-butyldimethylsilyl)-D-xylofuranose dithioaceta124
Proceeding as previously described for 14, a solution of 23 (4.8 g, 11.76 mmol) in anhydrous
pyridine (15 ml) was treated with TsC1 (4.02 g, 21.17 mmol) to give a crude reaction product (6.3
g) which was subjected to flash chromatography. Elution with a 9:1 mixture of hexane and AcOEt
afforded pure 24 (5.3 g, 80% yield), as a liquid: [Ot]D20=- 17.4 (c 1.1, CHCI3); IH NMR ~i 7.80 (d,
2H, J=8.3 Hz), 7.33 (d, 2H, J=8.0 Hz), 4.76 (t, IH, J=0.9 Hz), 4.54 (d, IH, J=4.0 Hz), 4.19 (rid, 1H,
J=9.6 and 4.1 Hz), 4.08 (dd, 1H, J=10.5 and 2.6 Hz), 3.74 (t, 2H, J=10.7 Hz), 2.52 (dd, 2H, J=6.8
and 4.7 Hz), 2.43 (s, 3H), 2.39 (dd, 2H, J=6.8 and 3.0 Hz), 1.52-1.90 (m, 2H), 0.96 (d, 6H, J=6.5
Hz), 0.88 (d, 6H, J=6.7 Hz), 0.86 (s, 9H), 0.11 (s, 3H), 0.07 (s, 3H). 13C NMR 6 145.71, 134.08,

Difunctionalised oxirane systems
1619
130.42, 128.67, 85.43, 81.87, 75.71, 75.62, 50.85, 40.43, 38.40, 29.44, 29.01, 26.22, 22.92, 22.84,
22.69, 22.34, 18.37. Anal. Calcd for C26H4605S3Si: C, 55.47; H, 8.24. Found: C, 55.29; H, 7.93.
2,5-Anhydro-3-O-tosyl-4-(O-t-butyldimethylsilyl)-D-xylofilranose
25
Following the procedure previously described for the synthesis of 8, the treatment of 24 (6.0 g,
10.7 mmol) in MeCN (100 ml) with HgCI2 (6.4 g, 23.5 mmol) and HgO (2.5 g, 11.5 mmol) in a 4:1
mixture of MeCN and water (160 ml) afforded a crude liquid product (3.64 g, 85% yield) consisting
of practically pure aldehyde 25 which was directly utilized in the next step without any further
purification: IH NMR 6 9.45 (d, IH, J=1.2 Hz), 7.62-7.71 (m, 2H), 7.26-7.34 (m, 2H), 4.76 (dd, 1H,
J = l . l and 3.7 Hz), 4.48---4.51 (m, IH), 4.37 (dd, IH, J=1.3 and 3.7 Hz), 4.22 (dd, 1H, J=9.6 and 3.4
Hz), 3.81 (d, 1H, J=9.5 Hz), 2.39 (s, 3H), 0.79 (s, 9H), 0.04 (s, 3H), 0.02 (s, 3H). n3C NMR 6 199.80,
146.41, 132.90, 130.74, 128.70, 85.49, 83.99, 76.46, 76.17, 26.26, 22.40, 18.51, -4.14, -4.41.
2,5-Anhydro-3-O-tosyl-2-(O-t-bu~ldimethylsilyl)-L-.~.lito126
Proceeding as previously described for the preparation of 9, the treatment of aldehyde 25 (3.64
g, 9.1 mmol) in anhydrous ether (160 ml) with 10 M BH3.MezS (2.3 ml) afforded a crude liquid
product (3.5 g, 95% yield) consisting of practically pure alcohol 26 which was directly utilized in the
next step without any further purification. An analytical sample (0.10 g) of crude 26 was purified by
flash chromatography: elution with a 6:4 mixture of hexane and AcOEt afforded pure 26, as a liquid:
[Ot]D20=-4.12 (c 1.48, CHCI3); IH NMR ~ 7.80 (d, 2H, J=8.2 Hz), 7.37 (d, 2H, J--8.1 Hz), 4.65 (d,
IH, J=2.8 Hz), 4.28-4.30 (m, IH), 4.18 (ddd, 1H, J=8.4, 6.2 and 3.2 Hz), 4.07 (dd, IH, J=9.2 and
3.9 Hz), 3.62-3.73 (m, 3H), 2.46 (s, 3H), 0.82 (s, 9H), 0.02 (s, 3H), 0.01 (s, 3H). t3c NMR c3 146.22,
133.48, 130.79, 128.64, 85.23, 80.01, 76.73, 74.76, 60.91,26.23, 22.41, 18.48, 4.00. Anal. Calcd for
C18H3006SSi: C, 53.70; H, 7.51. Found: C, 53.91; H, 7.22.
1,4-Anhydro-3-O-tosyl-2-(O-t-butyldimethylsilyl)-5-O-benzyl-L-:~Tlito127
a) Proceeding as previously described for the synthesis of 10, the treatment of a suspension of Nail
(1.4 g of a 60% dispersion in mineral oil, 35.0 mmol) in anhydrous THF (90 ml) containing benzyl
bromide (1.45 ml, 12.19 mmol) with a solution of alcohol 26 (4.90 g, 12.2 mmol) in anhydrous THF
(22 ml) afforded a crude liquid product (5.7 g) which was subjected to flash chromatography. Elution
with a 9:1 mixture of hexane and AcOEt afforded pure 27 (5.1 g, 85% yield), as a liquid: [0qD20=+8.15
(c 1.08, CHCI3); IH NMR 6 7.76 (d, 2H, J=8.4 Hz), 7.28-7.35 (m, 7H), 4.63 (dd, 1H, J=3.1 and 1.1
Hz), 4.45 and 4.41 (ABdd, 2H, J=l 1.9 Hz), 4.40 (dd, 1H, J=9.7 and 6.9 Hz), 4.27 (ddd, 1H, J=8.6,
6.5 and 3.2 Hz), 4.12 (dd, IH, J=9.4 and 4.1 Hz), 3.66 (dd, IH, J=9.5 and 1.2 Hz), 3.42-3.62 (m, 2H),
2.41 (s, 3H), 0.84 (s, 9H), 0.04 (s, 3H), 0.03 (s, 3H). 13C NMR 8 145.82, 138.53, 133.87, 130.58,
129.04, 128.52, 128.42, 128.33, 85.61, 78.68, 76.51, 75.00, 74.20, 68.62, 26.31, 22.33, 18.51, -4.22,
-4.41. Anal. Calcd for C25H3606SSi: C, 60.94; H, 7.36. Found: C, 60.84; H, 7.51.
b) Proceeding as previously described for the preparation of 14, the treatment of alcohol 13 (0.225
g, 0.67 mmol) in anhydrous pyridine (1.0 ml) with TsCI (0.25 g, 1.33 mmol) afforded crude tosylate
27 (0.32 g) which was purified by flash chromatography as in a) to give pure tosylate 27 (0.25 g).
1,4-Anhydro-3-O-tosyl-5-O-benzyl-L-©'lito117
Proceeding as previously described for the preparation of 15, a solution of 27 ( 1.6 g, 3.25 mmol) in
MeCN (16 ml) was treated with 48% aqueous HBF4 (0.95 nal) to give a crude solid product (1.15 g,
94% yield) consisting of practically pure hydroxy tosylate 17, as a solid, m.p. 70--71 °C (from hexane):
[0qD20=+38.98 (c 1.18, CHCI3); IR (CC14) 3614 cm -I (free OH); 1H NMR ~ 7.77 (d, 2H, J=8.3
Hz), 7.23-7.38 (m, 7H), 4.77 (dd, IH, J=4.0 and 1.4 Hz), 4.50-4.52 (m, IH), 4.40 and 4.49 (ABdd,
2H, J=12.0 Hz), 4.15-4.28 (m, 2H), 3.66 (dd, 1H, J=9.9 and 3.0 Hz), 3.40-3.57 (m, 2H), 2.40 (s,
3H). 13C NMR ~i 146.01,138.40, 133.48, 130.62, 129.03, 128.51,128.32, 85.88, 78.74, 76.53, 74.12,
73.68, 68.31, 22.34. Anal. Calcd for C19H2206S: C, 60.30 H, 5.86. Found: C, 60.52; H, 5.55.

1620
P. CROTTI et aL
1,4;2,3-Dianhydro-5-O-benzyl-L-ribitol 2
The treatment of a solution of 17 (1.32 g, 3.49 mmol) in anhydrous benzene (35 ml) with t-BuOK
(0.39 g × 2) afforded a liquid product consisting of pure epoxide (0.675 g, 94% yield), as a liquid:
[0t]D20=+16.73 (c 1.3, CHCI3); IH NMR ~i 7.25-7.36 (m, 5H), 4.54 (s, 2H), 4.21 (t, 1H, J=4.4 Hz),
3.92 (dd, 2H, J=10.2 Hz), 3.78 (dd, 2H, J=10.8 and 3.4 Hz), 3.52-3.61 (m, 2H). 13C NMR 5 138.48,
129.02, 128.42, 128.14, 77.33, 74.10, 70.92, 68.41, 58.53, 57.02. MS (m/e) 206 (M÷), 181, 145, 117,
91, 85, 69, 65. Anal. Calcd for C12H1403: C, 69.89; H, 6.84. Found: C, 69.66; H, 6.50.
1, 4-Anhydro-5-O-benzyl-L-~,lito116
A solution of ether 10 (0.88 g, 1.90 mmol) in MeCN (8.0 ml) was treated with 48% aqueous
HBF4 (0.8 ml) and the reaction mixture was stirred for 2 h at r.t. Solid NaHCO3 and ether were
added: evaporation of the washed (saturated aqueous NaHCO3) organic solution afforded a crude solid
product (0.36 g) consisting of diol 16, which was recrystallized from hexane to give pure (0.27 g), as a
solid, m.p. 72-74.5°C: [OQD20=-3.63 (c 1.10, CHC13); IH NMR ~5 7.24-7.35 (m, 5H), 4.54 and 4.58
(ABdd, 2H, J=12.4 Hz), 4.14-4.19 (m, 4H), 3.63-3.88 (m, 3H). 13C NMR 8 137.94, 129.21,128.67,
128.55, 79.15, 78.34, 74.59, 74.02, 69.59. Anal. Calcd for C12H1604: C, 64.27; H, 7.19. Found: C,
63.96; H, 7.39.
Monotosylation reaction of diol 16
A solution of diol 16 (0.84 g, 3.75 mmol) in anhydrous pyridine (11 ml) was treated at 0°C with
TsCI (0.75 g, 3.95 mmol) and the reaction mixture was stirred at r.t for 48 h. Dilution with ether and
evaporation of the washed (10% aqueous HCI, saturated aqueous NaHCO3 and brine) organic solution
afforded a crude oily product (1.25 g) consisting of a 57:43 mixture (1H NMR) of the monotosylates
15 and 17 which was subjected to flash chromatography. Elution with a 1:1 mixture of hexane and
AcOEt gave pure 15 (0.46 g) and 17 (0.42 g).
Acknowledgements
This work was supported by the Consiglio Nazionale delle Ricerche (CNR) and the Ministero della
Universit~ e della Ricerca Scientifica e Tecnologica (MURST), Roma.
References
1. a) Katsuki, T.; Sharpless, K.B.J. Am. Chem. Soc. 1980, 102, 5974-5976. b) Jacobsen, E.N.; Zhang,
W.; Muci, A.R.; Ecker, J.R.; Deng, L. J. Am. Chem. Soc. 1991, 113, 7063-7064, and references
therein.
2. Gorzynski Smith, J. Synthesis 1984, 629-656.
3. a) Colombini, M.; Crotti, P.; Di Bussolo, V.; Favero, L.; Gardelli, C.; Macchia, E; Pineschi, M.
Tetrahedron 1995, 51, 8089-8112. b) Chini, M.; Crotti, E; Gardelli, C.; Macchia, E J. Org. Chem.
1994, 59, 4131-4137. c) Chini, M.; Crotti, P.; Flippin, L.A.; Gardelli, C.; Giovani, E.; Macchia, E;
Pineschi, M. J. Org. Chem. 1993, 58, 1221-1227. d) Flippin, L.A.; Brown, P.A.; Jalali-Araghi. K.
J. Org. Chem. 1989, 54, 3588-3596 and references therein, e) Caron, M; Carlier, P.R.; Sharpless,
K.B.J. Org. Chem. 1988, 53, 5185-5187. f) Caron, M.; Sharpless, K.B.J. Org. Chem. 1985, 50,
1557-1560. g) Chong, J.M.; Sharpless, K.B.J. Org. Chem. 1985, 50, 1560-1563. h) Behrens,
C.H; Sharpless, K.B.J. Org. Chem. 1985, 50, 5696-5704.
4. For our regiochemical studies, racemic epoxides 1 and 2 would have been sufficient as in other
cases.3 However, due to the easy availability of the starting compound in an enantiopure form
[D(+)-xylose], enantiopure epoxides 1 and 2 were more advantageously prepared instead of the
racemic ones.
5. The results of the regiochemical behavior of epoxides 1 and 2 together with those of other related
oxirane systems will appear in a forthcoming paper.
6. a) Cleophax, J.; Gero, S.D.; Sepulchre, A.M. Acad. Sci. Paris, Ser. C 1968, 267, 162-165. b)
Montgomery, J.A.; Thomas, H.J.J. Org. Chem. 1978, 43, 541-544. c) Plavec, J.; Tong, W.;

1621
Difunctionalised oxirane systems
Chattopadhyaya, J. J. Am. Chem. Soc. 1993, 115, 9734-9746. d) Miljkovic, D.A.; Velimirovic,
S.S.J. Serb. Chem. Soc. 1988, 53, 31-36.
7. Defaye, J. Bull. Soc. Chim. Fr. 1964, 2686-2689.
8. Corey, E.J.; Erickson, B.W.J. Org. Chem. 1971, 36, 3553-3560.
9. The crude Mosher's ester of alcohol 9 showed the presence of only one diastereoisomer (1H NMR).
10. a) Batten, R.J.; Dixon, A.J.; Taylor, R.J.K. Synthesis 1980, 234-236. b) Greene, T.W.; Wuts,
P.G.M. Protective Groups in Organic Synthesis 2nd ed.; Wiley-Interscience, New York, 1991, p
77-83. c) Pilcher, A.S.; Hill, D.K.; Shimshock, S.J.; Waltermire, R.E.; DeShong, E J. Org. Chem.
1992, 57, 2492-2495.
11. Diol 16 was present at an extent not higher than 2-3% (IH NMR). Succinimide (from NBS) was
also present.
12. For example, the reaction of ether 10 with TBAF in THF at - 10°C afforded a 75:25 mixture
of alcohols 12 and 13 (see Experimental). Alcohol 13 can be utilized for the synthesis of trans
epoxide 2 (Scheme 4).
13. Czernecki, S.; Georgoulis, C.; Provelenghiou, C. Tetrahedron Lett. 1976, 3535-3536.
14. a) Torisawa, Y.; Shibasaki, M.; Ikegami, S. Tetrahedron Lett. 1979, 1865-1868. b) Colvin, E.
Silicon in Organic Chemistr),, Butterworths; London, 1981, p 187-188.
15. a) Suh, H.; Wilcox, C.S.J. Am. Chem. Soc. 1988, 110, 470-481. b) Nishiyama, S.; Shizuri, Y.;
Yamamura, S.; Terada, Y.; Kawai, K.; Furukawa, H. Tetrahedron Lett. 1985, 26, 6239--6242.
16. Zinner, H.; Rembarz, G.; Linke, H.-W.; Ulbricht, G. Chem. Ber. 1957, 90, 1761-1768.
17. Zinner, H.; Brandhoff, H.; Schmandke, H.; Kristen, H.; Haun, R. Chem. Ber. 1959, 92, 3151-3155.
(Received in UK 10 March 1997)