Regiochemical control of the ring opening of 1,2-epoxides by means of chelating processes. Part 17: Synthesis and opening reactions of cis- and trans-oxides derived from (2S,6R)-2-benzyloxy-6-methyl-3,6-dihydro-2H-pyran, (2R,6R)- and (2S,6R)-2-methoxy-6-m

Article abstract of DOI:10.1016/S0040-4020(02)00578-1

The regiochemical behavior of the title deoxy anhydrosugars, prepared in an enantioselective way starting from methyl α-D-glucopyranoside, was examined in opening reactions, both under standard and chelating conditions. The results clearly indicate the in

Full text of DOI:10.1016/S0040-4020(02)00578-1

TETRAHEDRON
Pergamon
Tetrahedron 58 82002) 6069±6091
Regiochemical control of the ring opening of 1,2-epoxides by
means of chelating processes. Part 17: Synthesis and opening
reactions of cis- and trans-oxides derived from
ꢀ2S,6R)-2-benzyloxy-6-methyl-3,6-dihydro-2H-pyran,
ꢀ2R,6R)- and ꢀ2S,6R)-2-methoxy-6-methyl-5,6-dihydro-2H-pyran
Paolo Crotti,p Valeria Di Bussolo, Lucilla Favero, Franco Macchia and Mauro Pineschi
Á
Dipartimento di Chimica Bioorganica e Biofarmacia, Universita di Pisa, Via Bonanno 33, I-56126 Pisa, Italy
Received 24 February 2002; revised 15May 2002; accepted 6 June 2002
AbstractÐThe regiochemical behavior of the title deoxy anhydrosugars, prepared in an enantioselective way starting from methyl
a-d-glucopyranoside, was examined in opening reactions, both under standard and chelating conditions. The results clearly indicate the
in¯uence of the reaction conditions and the importance of the relative orientation of the methyl group with respect to the oxirane ring on the
regiochemical outcome of these epoxides. An useful inversion of regioselectivity is obtained in some cases. q 2002 Elsevier Science Ltd. All
rights reserved.
1. Introduction
behavior in opening reactions with nucleophiles. Enantio-
meric methyl glycosides of epoxides 1±4 were previously
synthesized and the corresponding regiochemical behavior
examined in nucleophilic opening reactions carried out only
under standard not chelating reaction conditions.3,4 As a
consequence, a more detailed examination of the regio-
chemical behavior of the oxirane system corresponding to
epoxides 1±4, also including opening reactions carried out
under chelating conditions, appeared to us deserving of
consideration.4
Epoxides constitute a valuable synthetic tool for the
construction of b-hydroxy-substituted functionalities by
means of their opening reactions with a large variety of
nucleophiles. While on the one hand the stereoselectivity
of the opening process is, at least in the aliphatic and cyclo-
aliphatic systems, under complete anti-stereocontrol, the
regioselectivity depends on several electronic and confor-
mational factors. We found that the presence of an O-func-
tionality in a suitable position with respect to the oxirane
ring and appropriate opening reaction conditions can direct
the regioselectivity of the opening process by in¯uencing
the conformational equilibrium inside the reacting epoxide.1
Diastereoisomeric epoxides cis,trans-3 and trans,cis-4,5
formally derived from 82S,6R)-2-benzyloxy-6-methyl-3,6-
dihydro-2H-pyran 89), are regioisomers of the diastereo-
isomeric epoxides 5±8, formally derived from 82R,6R)-
810) 8epoxides cis,cis-5 and trans,trans-6) and 82S,6R)-2-
methoxy-6-methyl-5,6-dihydro-2H-pyran 811) 8epoxides
cis,trans-7 and trans,cis-8). Epoxides 3 and 4 are dia-
stereoisomers of the previously studied epoxides cis,cis-1
and trans,trans-2. The choice of methyl glycosides in the
case of epoxides 5±8, unlike the benzyl glycosides utilized
in the case of epoxides 3 and 4, and in the previously studied
epoxides 1 and 2 was simply based on the easy availability
of the non-racemic starting material 8vide infra) necessary
for their preparation.6
Our interest in the chemistry of epoxides, particularly when
applied to naturally occurring systems, recently led us to
examine the chemical behavior of the diastereoisomeric
deoxy anhydrosugars 1 and 2, thus obtaining some prelimin-
ary information about the chemical behavior of this class of
compounds.2 In view of the importance of these oxirane
systems for the construction of derivatized branched anhy-
drosugars, we synthesized the chiral, non-racemic, deoxy
anhydropyranosides 3±8, a sort of branched sugars, like 1
and 2, because of the presence of a methyl as the C85)-
substituent, and examined their stereo- and regiochemical
2. Results
Keywords: deoxy anhydrosugars; epoxides; regioselectivity; opening
reactions.
Corresponding author. Tel.: 139-050-44074; fax: 139-050-43321;
e-mail: crotti@farm.unipi.it
p
Glycal 82)-17, the advanced precursor for the synthesis of
both epoxides 3 and 4, was prepared from the commercially
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020802)00578-1

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P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
available tri-8O-acetyl)-d-glucal [82)-12], in accordance
with a previously described procedure through the triol
13, the monotosylate 14, the diacetate 81)-15 and the iodide
82)-16, as shown in Scheme 1.7 Because of the lengthiness
of this procedure, we envisaged a more direct approach to
diacetate 81)-15, consisting of an initial selective hydrolysis
of glucal 82)-12 by lipase CCL to give the primary alcohol
82)-18, then transformed into 81)-15, by the TsCl/Py
protocol.
alcohol8 afforded a 27:73 mixture of a- and b-benzyl glyco-
sides 81)-19 and 81)-20. a-Glycoside 81)-20 was separated
and dehalogenated with Bu3SnH to give the a-glycoside
81)-21 which was hydrolyzed 8MeONa/MeOH) to the
desired diol 81)-22a, the ultimate precursor of epoxides 3
and 4 8Scheme 1).
The consistently different steric hindrance of the secondary
hydroxyl functionalities present in diol 81)-22a allowed a
stereoselective synthesis of epoxide 3 8Scheme 2). In fact,
the reaction of 81)-22a with TBDMS-Cl 81 equiv.) in DMF
The reaction of 82)-17 with NBS in the presence of benzyl
Scheme 1.

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6071
Scheme 2.
led only to the mono C83)-O-TBS protected derivative 81)-
23, subsequently transformed into the mesylate 81)-24.
Deprotection of 81)-24 by TBAF afforded the trans
hydroxy mesylate 81)-25 which was subjected to base-
catalyzed cyclization to give epoxide 81)-3. On the other
hand, epoxide 81)-4 was obtained only by the monotosyl-
ation of diol 81)-22a, giving a 73:17 mixture of monotosyl-
ates 81)-26 and 81)-27, accompanied by a small amount
of ditosylate 81)-28 810%), which were directly
cyclized 8basic Amberlyst) to a corresponding mixture of
epoxides 81)-4 and 81)-3. Separation of this mixture
by ¯ash chromatography afforded pure epoxide 81)-4
8Scheme 2).
previously described procedure,9a treatment of 81)-29a
with SO2Cl2, followed by reaction of the intermediate di-
chlorosulfate with catalytic NaI, afforded the dichloro diol
81)-30a which was dehalogenated 8H2/Ni-Raney/KOH) to
the desired 2,3-diol 81)-31a.9,10 Actually, in the dehalo-
genation process of 81)-30a, a certain amount of the dioxa-
bicyclic compound 81)-33 810%) was obtained. Compound
81)-33 reasonably arises from the monochloro diol 32, the
reaction intermediate deriving from a faster hydrogenolysis
rate of the secondary C84)±Cl bond of 81)-30a, which can
in part intramolecularly cyclize, in alkaline reaction condi-
tions through its diaxial conformer 32b, to 81)-33.
Compound 81)-33 can be separated from 81)-31a by
¯ash chromatography 8Scheme 3).
The diol 81)-31a necessary for the synthesis of epoxides 7
and 8 was prepared starting from commercially available
Diol 81)-31a was transformed in a completely regio-
selective way into the monoacetate 81)-34a by means of
methyl a-d-glucopyranoside [81)-29a]. Following
a
Scheme 3.

6072
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
Scheme 4.
a transesteri®cation process catalyzed by lipase PS.
Treatment of 81)-34a with MsCl/Py afforded the acetoxy
mesylate 81)-35a, subsequently hydrolyzed to the inter-
mediate hydroxy mesylate 36a which was not separated
but directly cyclized under alkaline conditions to epoxide
81)-8.11 Epoxide 81)-8 can also be prepared in a straight-
forward, completely stereoselective way with a satisfactory
yield 862%) by application of the Mitsunobu reaction proto-
col 8PPh3-DEAD)12 to diol 81)-31a, indicating an initial
completely regioselective reactivity of the C83)±OH in
these conditions 8Scheme 3).
No selective synthesis was envisaged for epoxide 81)-7
which was prepared only by monotosylation of diol
Scheme 5.

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6073
Scheme 6.
81)-31a, giving an 85:15 mixture of tosylates 37 and 38
which were not separated, but directly cyclized to a
corresponding mixture of epoxides 81)-7 and 81)-8, from
which epoxide 81)-79d,11 was obtained pure by ¯ash
chromatography 8Scheme 4).13
of carboxonium ion 41, selectively attacked by the nucleo-
phile 8I2) on the less hindered a-face 8axial attack) to give
the a-iodide 42.18 Subsequent SN2 displacement by MeOH
affords diacetate 81)-39b, as observed 8Scheme 5). Di-
acetate 81)-39b is then hydrolyzed to the desired 2,3-diol
82)-31b19 which constitutes the effective advanced
synthetic intermediate for the synthesis of epoxides 5 and
6. Transacetylation of 82)-31b catalyzed by lipase PS
afforded regioselectively the monoacetate 81)-40b,20
which was transformed into mesylate 82)-43b, and then
hydrolyzed to the hydroxy mesylate 82)-44b. Subsequent
cyclization of 82)-44b under alkaline conditions afforded
epoxide 82)-5 8Scheme 5).21
For the synthesis of diastereoisomeric epoxides 82)-5 and
82)-6, we needed diol 82)-31b. We initially thought of
applying to the commercially available methyl-b-d-gluco-
pyranoside [82)-29b] the same protocol previously
employed with anomer 81)-29a for the synthesis of diol
81)-31a. Unfortunately, the initial reaction of 82)-29b
with SO2Cl2 followed by reduction with NaI and hydro-
genolysis afforded only a complex reaction mixture contain-
ing the desired diol 82)-31b in a decidedly unsatisfactory
The reaction of diol 82)-31b under Mitsunobu operating
conditions proceeds, as in the corresponding a-system,
with initial completely selective reactivity of the C83)±
OH22 to give epoxide 82)-6,21 as the only reaction product.
As a consequence, it was possible, in this system, to proceed
to the synthesis of both epoxides 82)-5 and 82)-6 in a
completely stereoselective fashion. Moreover, it is to be
noted that both couples of diastereoisomeric epoxides 5±8
may be synthesized starting from a single precursor, the 2,3-
diol 81)-31a, easily obtained from a commercially avail-
able and cheap starting material, such as methyl a-d-gluco-
pyranoside [81)-29a].
1
yield 810%, H NMR) 8Scheme 5).14
The problem of the synthesis of these epoxides was effec-
tively solved by applying to diacetate 81)-39a16a 8obtained
by acetylation of 81)-31a) a modi®cation of a procedure
previously utilized for the b-glycosidation of similar
substrates.17 In this way, the reaction of diacetate 81)-39a
with Me3SiI, followed by treatment with MeOH in the
presence of Ag2CO3, led to the anomeric diacetate 81)-
39b,16b in a completely stereoselective way. This result is
rationalized by admitting the initial intermediate formation

6074
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
Scheme 7.
As for the b-system represented by epoxides 5 and 6, we had
initially envisaged also a non-enantioselective 8racemic)
synthetic procedure, with the possibility of transforming it
into an enantioselective one, utilizing an asymmetrical
approach in the synthetic step in which the ®rst stereogenic
centre is introduced 8vide infra).23 The racemic synthetic
sequence utilizes glycal 8^)-48 which was obtained by
benzylation 8BnBr/NaH) of alcohol 8^)-47, prepared as
previously described.23 Oxidation of 8^)-48 with dimethyl
dioxirane 8DMDO) generated in situ 8oxonew±MeOH±
acetone) leads to the intermediate, unseparated epoxide
8^)-49a, which undergoes an opening reaction with the
MeOH present in the reaction mixture to give a 9:1 mixture
of the two anomeric methyl glycosides 8^)-50b and 8^)-
50a, subsequently transformed by acetylation into a corre-
sponding mixture of acetates 8^)-51b and 8^)-51a. The 1H
NMR spectra of the mixture of 8^)-51a and 8^)-51b show
that these two compounds have the same con®guration at
C82) 8a gluco con®guration), thus indicating that the corre-
sponding methyl glycosides 8^)-50a and 8^)-50b are really
opening products of the same intermediate epoxide 8^)-
49a, the former being the product of retention and the latter
the product of inversion 8Scheme 6).24
The 9:1 mixture of benzyloxy acetates 8^)-51b and 8^)-
51a was deprotected by hydrogenolysis to give only
hydroxy acetate 8^)-34b which was transformed into
mesylate 8^)-35b. Alkaline hydrolysis of 8^)-35b
8MeONa/MeOH) followed by cyclization with t-BuOK in
anhydrous benzene afforded pure epoxide 8^)-6. On the
Table 1. Regioselectivity of the ring opening reactions of epoxides 1, 3, 5, and 7
Entry
Epoxide
Reagents
Solvent
Reaction conditions 88C)a
Reaction time
C-2 or C-4 product
C-3 product
Yield 8%)
1
2
3
4
1
1
NaN3/NH4Cl
NaN3/LiClO4
MeONa
MeOH/H2O
MeCN
MeOH
MeOH
MeOH
EtOH
MeCN
MeOH
MeCN
MeOH/H2O
MeCN
MeOH
MeOH
EtOH
MeCN
MeOH
MeCN
MeOH/H2O
MeCN
MeOH
MeOH
EtOH
MeCN
MeOH
MeCN
MeOH/H2O
MeCN
MeOH
MeOH
EtOH
A 880)
B 880)
A 880)
A 8rt)
B 880)
A 880)
B 880)
A 8rt)
B 880)
A 880)
B 880)
A 880)
B 880)
A 880)
B 880)
A 8rt)
B 880)
A 880)
B 880)
A 880)
B 880)
A 880)
B 880)
A 8rt)
18 h
18 h
4 h
,1b,c,d
,1b,c
.99
.99
.99
.99
95
97
99
33
,1b,c,d
,1b,c
MeOH/H2SO4
1 h
5MeOH/LiClO
6
7
8
18 h
7 days
18 h
18 h
18 h
18 h
18 h
24 h
24 h
30 h
18 h
18 h
3 days
24 h
24 h
1 h
24 h
5days
18 h
18 h
24 h
18 h
18 h
3 h
complex mixturec
4
1
1
3
3
3
3
5
5
5
5
Et2NH
,1b,c,d
,1b,c
,1b,c
.99
.99
.99c
94
95
95
99
97
Et2NH/LiClO4
PhSH/NEt3
PhSH/LiClO4
NaN3/NH4Cl
NaN3/LiClO4
MeONa
9
complex mixture
10
11
12
13
14
15Et
16
17
18
19
20
21
22
23
24
7b,d
5b
93
9599
79
.99
.99
.99
93
21b,d
,1b
,1b,d
,1b
7b
87
30
97
95
99
MeOH/LiClO4
Et2NH
2NH/LiClO4
PhSH/NEt3
PhSH/LiClO4
NaN3/NH4Cl
NaN3/LiClO4
MeONa
MeOH/LiClO4
Et2NH
Et2NH/LiClO4
PhSH/NEt3
complex mixture
,1e
,1e
,1e
,1e
,1e
,1e
,1e
,1e
,1e
,1e
,1e
,1e
,1e
,1e
,1e
,1e
.99
.99
.99
.99
.99
.99
.99
.99
.99
.99
.99
.99
.99
.99
.99
.99
97
80
70
35
84
92
99
99
99
88
99
39
99
99
99
86
25PhSH/LiClO
B 880)
A 880)
B 880)
A 880)
B 880)
A 880)
B 880)
A 8rt)
4
26
27
28
29
30
31
32
33
7
7
7
7
NaN3/NH4Cl
NaN3/LiClO4
MeONa
MeOH/LiClO4
Et2NH
Et2NH/LiClO4
PhSH/NEt3
PhSH/LiClO4
18 h
2 days
2 h
24 h
24 h
MeCN
MeOH
MeCN
B 880)
a
A: standard reaction conditions; B: chelating reaction conditions, Ref. 4.
C-4 product.
Ref. 2.
For the related results obtained with the corresponding enantiomeric methyl glycosides, see Ref. 3.
C-2 product.
b
c
d
e

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
Table 2. Regioselectivity of the ring opening reactions of epoxides 2, 4, 6 and 8
6075
Entry
Epoxide
Reagents
Solvent
Reaction conditions 88C)a
Reaction time
C-2 or C-4 product
C-3 product
Yield 8%)
94
1
2
3
2
NaN3/NH4Cl
NaN3/LiClO4
NaN3/LiClO4
MeOH/H2SO4
MeOH
MeOH/LiClO4
Et2NH
Et2NH/LiClO4
PhSH/NEt3
PhSNa/LiClO4
NaN3/NH4Cl
NaN3/LiClO4
MeONa
MeOH/H2O
MeCN
MeOH
A 880)
B 880)
B 880)
A 8rt)
18 h
18 h
18 h
1 h
69b,c,d
35b,c
18b,c
31
6595
82
41
95
41
83
4
5MeONa
6
7
8
2
MeOH
59b,c
b,c,d
A 880)
24 h
21
79
MeOH
EtOH
B 880)
A 880)
B 880)
A 8rt)
B 880)
A 880)
B 880)
A 880)
A 8rt)
B 880)
B 880)
A 880)
B 880)
A 8rt)
B 880)
A 880)
B 880)
A 880)
B 880)
A 880)
B 880)
A 8rt)
24 h
30 h
18 h
18 h
3 days
18 h
18 h
4 h
complex mixturec
2
2
4
4
45b,c,d
15b,c
65b,c
50b,c
13b,d
76b
55
60
MeCN
MeOH
MeCN
MeOH/H2O
MeCN
MeOH
MeOH
MeOH
MeCN
EtOH
MeCN
MeOH
MeCN
MeOH/H2O
MeCN
MeOH
MeOH
EtOH
MeCN
MeOH
MeCN
MeOH/H2O
MeCN
MeOH
MeOH
EtOH
8596
3594
5
87
24
9
10
11
12
13
14
0
75
99
99
99
4b,d
96
MeOH/H2SO4
1 h
complex mixture
15MeOH/LiClO
16
18 h
18 h
7 days
18 h
18 h
18 h
24 h
24 h
1 h
18 h
4 days
18 h
24 h
24 h
18 h
18 h
4 h
90b
66b
15b,d
46b
5b
10
34
855
5
9599
4599
67
63
62
87
23
4
MeOH/LiClO4
Et2NH
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
4
4
6
6
6
6
8
8
8
8
2
Et2NH/LiClO4
PhSH/NEt3
PhSH/LiClO4
NaN3/NH4Cl
NaN3/LiClO4
MeONa
4
99
55b
33e
37e
38e
92
45
97
MeOH/LiClO4
Et2NH
complex mixture
33e
67
68
66
5
77
82
70
97
84
70
67
33
79
10
99
1
90
86
95
50
80
35
98
93
Et2NH/LiClO4
PhSH/NEt3
PhSH/LiClO4
NaN3/NH4Cl
NaN3/LiClO4
MeONa
MeOH/LiClO4
Et2NH
Et2NH/LiClO4
PhSH/NEt3
PhSH/LiClO4
32e
34e
49e
23e
18e
30e
3e
B 880)
A 880)
B 880)
A 880)
B 880)
A 880)
B 880)
A 8rt)
11
18 h
8 days
5h
18 h
18 h
16e
30 e
33e
67e
MeCN
MeOH
MeCN
B 880)
a
A: Standard reaction conditions; B: Chelating reaction conditions, Ref. 4.
C-4 product.
Ref. 2.
For the related results obtained with the corresponding enantiomeric methyl glycosides, see Ref. 3.
C-2 product.
b
c
d
e
other hand the 9:1 mixture of hydroxy ethers 8^)-50b and
8^)-50a can be utilized for the synthesis of diastereoiso-
meric epoxide 8^)-5. In fact, the treatment of this mixture
with MsCl afforded a corresponding mixture of mesylates
8^)-52b and 8^)-52a which were deprotected by hydroge-
nolysis to give the hydroxy mesylate 8^)-44b as the only
reaction product. Cyclization of 8^)-44b under alkaline
conditions afforded pure racemic epoxide 5 8Scheme 6).
chelating conditions.4 The results obtained are shown in
Tables 1 and 2, where for comparison also the results
previously obtained with epoxides 1 and 2 are reported,
too.2 The regiochemical results obtained with epoxides
1±4 under standard conditions 8MeONa/MeOH, NaN3/
NH4Cl, NHEt2/EtOH) are quite similar to the ones
previously obtained with the corresponding enantiomeric
methyl glycosides.3 The results indicate that the regio-
selectivity with epoxides 3±8, and with the previously
studied epoxides 1 and 2,2 is strongly in¯uenced by the
electron-withdrawing inductive effect of the nearby acetal
functionality, and that the sensitivity of epoxides 1±8 to
different operating conditions 8standard or chelating) is
closely linked to the structure and particularly to the
relationship between the oxirane moiety and the branched
chain 8the methyl group), and to the distance of the oxirane
ring from the acetal group.
As anticipated earlier, in order to transform the racemic
process described above into an enantioselective one, the
initial cycloaddition reaction between Danishefsky diene
and acetaldehyde was repeated in the presence of
8R,R)8salen)Cr8III)OTf complex 853).25a Contrary to expec-
tations based on previous corresponding results,25b the
cycloadduct, the dihydropyranone 46, was obtained only
with 57% ee. Attempts to increase the ee of the process
were unsuccessful 8Scheme 7).
In the presence of a cis relationship between the oxirane ring
and the methyl group, the regiochemical behavior of the
corresponding epoxides 1, 3, 5, and 7 is completely or
highly C-3 stereoselective to give C-3-products, inde-
pendently of the operating conditions and position of the
acetal OR group with respect to the oxirane ring, cis in
3. Discussion
Epoxides 3±8 were subjected to ring opening reactions with
some representative nucleophiles both under standard and

6076
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
Scheme 8.
Scheme 9.

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6077
Scheme 10.
epoxides 1 and 5 and trans in 3 and 7 8Table 1). With these
epoxides, in accordance with the FuÈrst±Plattner rule,
nucleophilic attack occurs on the C83) oxirane carbon,
through the corresponding more stable conformer a with
the methyl group equatorial,26 not only under standard
conditions, as previously observed with the corresponding
methyl glycosides of 1 and 3,3 but also under chelating
conditions. In fact, under chelating conditions, the
incursion of corresponding chelated structures such as
54±57, respectively, in which the more stable conforma-
sponding conformer a which allows the methyl group to be
equatorial 8Scheme 9). As a result of the the absence of a
strict correlation between the reactivity of the more stable
conformer a 8methyl group equatorial) and nucleophilic
attack on the more reactive C83)-oxirane carbon, as found
in epoxides 1, 3, 5, and 7, the regioselectivity observed with
epoxides 2, 4, and 8, with the only exception of 6,29 shows
an interesting dependence on the reaction conditions, due to
the incursion, under chelating conditions, of chelated
bidentate structures able to modify the regiochemical
behavior of these epoxides. While in the case of the
previously studied epoxide 2, the incursion of the only
possible structure 58 8Scheme 10) determines an increase
of C-3 products,2 in the case of epoxide 4, the incursion of
the more stable structure 59 determines a consistent increase
of C-4 products 8Table 2). In this framework, the behavior
of epoxide 8 is interesting in which the use of chelating
conditions determines an increase of the C-3 selectivity
tion a is still maintained, is reasonably admitted
8Scheme 8).27,28
In the presence of a trans relationship between the oxirane
ring and the methyl group, the regiochemical behavior of
the corresponding epoxides 2, 4, 6 and 8 is slightly different
8Table 2). In these epoxides, nucleophilic attack on the
electronically more favored C83) oxirane carbon, necessa-
rily occurring through the corresponding conformer b,
suffers from an 1,3-diaxial interaction between the incoming
nucleophile and the axial methyl group, as shown in 2, 4, 6,
and 8b 8Scheme 9), to the point that, under standard condi-
tions, some amounts 8up to 30%) of nucleophilic attack
occur at the electronically less favored C84)- 8epoxides 2
and 4), as previously observed and extensively discussed
with the corresponding enantiomeric methyl glycosides,3
or C82) oxirane carbon 8epoxides 6 and 8) through the corre-
2
8from 70 to 95%) with weak nucleophiles such as N3 and
MeOH, while the use of a strong nucleophile such as PhSH
determines a partial inversion of regioselectivity and an
increase 8up to 67%) of the amount of C-2 products
8Table 2, entries 29±36).
The interesting result obtained with epoxide 8 may be ratio-
nalized by admitting, under chelating conditions, the incur-
sion of two different types of chelated structures: structure

6078
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
60 in which the oxirane oxygen is linked through the
metal to the exocyclic OMe group and structure 61 in
which the oxirane oxygen and the endocyclic acetal oxygen
are coordinated through the metal 8Scheme 10). Weak
nucleophiles such as N32 and MeOH can attack only species
61 still allowing nucleophilic attack on the more reactive
C83)-oxirane carbon 8see above) 8Table 2, entries 29±32),
while strong nucleophiles such as PhSH, as a result of the
unfavorable 1,3-diaxial interaction with the axial methyl
group occurring in an attack on structure 61, can take
advantage of the presence in the reaction medium of the
less hindered structure 60 with consequent preferential
attack on the less reactive C82)-position 8Table 2, entries
5. Experimental
5.1. General
Melting points were determined on a Ko¯er apparatus and
are uncorrected. IR spectra for comparison between
compounds were registered on a Mattson 3000 FTIR
spectrophotometer. H and 13C NMR spectra were deter-
1
mined with a Bruker AC 200 spectrometer on CDCl3
solution using tetramethylsilane as the internal standard.
Preparative TLC were performed on 2.0 or 0.5mm
Macherey±Nagel DC-Fertigplatten UV254 silica gel plates.
All reactions were followed by TLC on Alugram SIL
G/UV254 silica gel sheets 8Machery±Nagel) with detection
by UV and/or by a 10% phoshomolybdic acid in EtOH.
Silica gel 60 8Machery±Nagel 230±400 mesh) was used
for ¯ash chromatography. All the reactions with compounds
sensitive to air and/or humidity were carried out under a
nitrogen or argon atmosphere and reagents were added via
syringe or cannula. Anhydrous solvents were distilled under
a nitrogen atmosphere immediately prior to use: THF and
toluene from sodium/benzophenone ketyl, and CH2Cl2 from
CaH2. Acetylation protocol: the product 80.050 g) in
anhydrous pyridine 80.8 mL) was treated at 08C with
Ac2O 80.5mL) and the resulting reaction mixture was left
18 h at rt. After dilution with toluene, all solvents were
removed under vacuum 8rotating evaporator). Glycal
82)-17,7a dichlorodiol 81)-30a9a were prepared as
previously described.
30
35and 36). The regiochemical behavior of epoxide 8 in
the reaction with strong and weak nucleophiles is very
similar to the one observed in the corresponding opening
reactions of the structurally related cis epoxide 62. Also in
that case, substantial amounts of C-2 products deriving from
nucleophilic attack on the electronically less favored
C82)-oxirane carbon were observed only under chelating
conditions and with strong nucleophiles such as PhSH,
2
while weak nucleophiles such as MeOH and N3 afforded
C-3 products under any 8standard or chelating) conditions.
A rationalization based on the incursion of the intermediate
chelated bidentate structure 63 and on considerations
similar to the ones presently utilized with the structurally
related species 60, admitted from 8, was correspondingly
given 8Scheme 10).1b
5.1.1. Diacetate ꢀ2)-18. A solution of 82)-tri-8O-acetyl)-d-
glucal 812) 84.0 g, 14.70 mol) in i-Pr2O 825mL), phosphate
buffer 8pH 7, 150 mL) and acetone 815 mL) was treated with
lipase CCL 81.30 g) and the reaction mixture was stirred at
rt for 16 h. Extraction with AcOEt of the ®ltered 8Celite)
reaction mixture and evaporation of the washed 8saturated
aqueous NaCl) organic extracts afforded a crude residue
which was subjected to ¯ash chromatography. Elution
with an 1:1 hexane/AcOEt mixture afforded pure ,2)-3,4-
di-,O-acetyl)-d-glucal 818) 83.10 g, 92% yield), as a liquid
4. Conclusion
A detailed examination of the regiochemical behavior of the
branched deoxy anhydro glycosides 1±8 allowed the
interpretation of the role of the methyl group on the regio-
chemical behavior of these epoxides. In accordance with
previous results from standard opening reactions with the
corresponding methyl glycosides of epoxides 1±4,3 when
the methyl is cis to the oxirane ring 8epoxides 1, 3, 5, and
7), the nucleophilic attack always occurs in all conditions
8standard or chelating) at the C83)-oxirane carbon, furthest
from the electron-withdrawing inductive effect of the acetal
functionality, with the epoxide reacting in its more stable
conformer a 8methyl group equatorial). On the contrary,
when the methyl group is trans to the oxirane ring 8epoxides
2, 4, 6, and 8), it makes the difference: in this case the
reactions are not completely C-3 regioselective and the
oxirane ring opening process may become sensitive to
reaction conditions. In fact, in these systems, under standard
conditions, attack on the electronically more favored
C83)-oxirane carbon necessarily occurs by the less stable
conformer b with the methyl group axial and consequent
unfavorable 1,3-diaxial interaction, to the point that the
alternative conformer a, bearing the methyl group equa-
torial, becomes competitive. Attack at the C82)- 8epoxides
6 and 8) or C84)-oxirane carbon 8epoxides 2 and 4) is conse-
quently observed to give substantial amounts of C-2 or C-4
products, respectively. Under chelating conditions, the
incursion of appropriate intermediate chelated structures
can modify the regioselectivity, affording additional
amounts of C-2 8from 8) or C-4 products 8from 2 and 4),
respectively.
8Found: C, 52.38; H, 6.42. C10H14O6 requires C, 52.17; H,
6.13). IR 34658OH), 1744 and 1746 cm
21
8CvO);
25
1
[a]D ˆ255.5 8c 1.38, CHCl3); H NMR d 6.49 8dd, 1H,
Jˆ6.1, 1.2 Hz), 5.41±5.50 8m, 1H), 5.22 8dd, 1H, Jˆ9.0,
6.5Hz), 4.81 8dd, 1H, Jˆ5.9, 2.8 Hz), 3.98±4.09 8m, 1H),
3.66±3.86 8m, 2H), 2.13 8s, 3H), 2.07 8s, 3H); 13C NMR d
170.77, 170.60, 145.91, 99.13, 76.72, 68.37, 67.88, 60.63,
21.16, 20.96.
5.1.2. Tosylate ꢀ1)-15. A solution of diacetate 82)-18
81.70 g, 7.40 mmol) in anhydrous pyridine 815mL) and
anhydrous CH2Cl2 815mL) was treated at 0 8C with TsCl
83.1 g, 16.3 mmol) and the reaction mixture was stirred at
the same temperature for 20 h. Dilution with CH2Cl2 and
evaporation of the washed 8saturated aqueous NaHCO3 and
NaCl) organic solution afforded a crude reaction product
which was subjected to ¯ash chromatography. Elution
with an 1:1 hexane/AcOEt mixture yielded pure ,1)-3,4-
di-,O-acetyl)-6-,O-tosyl)-d-glucal 815)7b,c 82.50 g, 88%
yield), as a solid, mp 106±1088C 8recrystallized from hex-
ˆ
25
ane/AcOEt). IR n 1755 and 1732 cm21 8CvO); [a]D
114.0 8c 1.2, CHCl3) [lit.7b mp 1088C, [a]D ˆ130 8c
25
1.1, CHCl3)].

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6079
5.1.3. Bromides ꢀ1)-19 and ꢀ1)-20. Following
a
5.1.5. Diol ꢀ1)-22a. The treatment of a solution of diacetate
81)-21 80.56 g, 1.74 mmol) in MeOH 820 mL) with MeONa
80.010 g) under stirring for 18 h at rt afforded, after evapora-
tion of the ®ltered organic solution, a crude product consist-
ing of diol 81)-22a 80.40 g), which was ®ltered through a
short silical gel column. Elution with AcOEt afforded pure
previously described procedure,8 a stirred solution of glycal
82)-177a 84.97 g, 23.2 mmol) in MeCN 840 mL) containing
benzyl alcohol 83.72 g, 34.5mmol) was treated at 0 8C with
NBS 84.95g, 27.8 mmol) and the resulting reaction mixture
was stirred at the same temperature for 1 h. Evaporation of
the solvent afforded a residue 87.44 g) consisting of a 73:27
mixture of bromides 20 and 19, which was subjected to ¯ash
chromatography. Elution with a 9:1 hexane/AcOEt afforded
pure bromides 81)-19 80.57 g, 6% yield) and 81)-20
84.80 g, 52% yield).
,1)-benzyl2,6-dideoxy-
80.34 g, 82% yield), as a solid, mp 112±114.58C 8recrystal-
a-d-glucopyranoside
822a)
lized from hexane/AcOEt) 8Found: C, 65.44; H, 6.34.
25
C13H18O4 requires C, 65.53; H, 7.61): [a]D ˆ1123.4 8c
1
1.1, CHCl3). IR 3365cm 21 8OH); H NMR d 7.20±7.41
8m, 5H), 4.93 8unresolved dd, 1H, Jˆ3.1 Hz), 4.67 8d, 1H,
Jˆ11.9 Hz), 4.44 8d, 1H, Jˆ11.9 Hz), 3.85±4.05 8m, 1H),
3.70 8dq, 1H, Jˆ9.0, 6.2 Hz), 3.11 8t, 1H, Jˆ9.0 Hz), 2.17
8ddd, 1H, Jˆ12.8, 5.4, 1.2 Hz), 1.70 8ddd, 1H, Jˆ12.8, 11.6,
3.6 Hz), 1.30 8d, 3H, Jˆ6.2 Hz); 13C NMR d 138.22,
129.04, 128.49, 128.35, 97.08, 78.38, 69.59, 69.41, 68.46,
38.29, 18.41.
,1)-Benzyl3,4-di-,O-acety)-l2-, b-bromo)-2,6-dideoxy-a-
d-mannopyranoside 820), a solid, mp 104±1068C 8recrys-
tallized from hexane/CHCl3) 8Found: C, 51.26; H, 4.96.
25
C17H21BrO6 requires C, 50.89; H, 5.28): [a]D ˆ152.3 8c
1
1.8, CHCl3). IR 1745cm 21 8CvO); H NMR d 7.20±7.40
8m, 5H), 5.13±5.28 8m, 2H), 5.06 8d, 1H, Jˆ1.2 Hz), 4.71
8d, 1H, Jˆ11.9 Hz), 4.54 8d, 1H, Jˆ11.9 Hz), 4.48 8dd, 1H,
Jˆ3.3, 1.2 Hz), 3.86±4.03 8m, 1H), 2.08 8s, 3H), 2.06 8s,
3H), 1.22 8d, 3H, Jˆ6.3 Hz); 13C NMR d 170.72, 170.39,
137.13, 129.17, 128.73, 99.57, 71.83, 70.39, 69.93, 67.68,
50.77, 21.48, 21.42, 18.08 81£Ph signal unresolved).
5.1.6. Monoprotection of diol ꢀ1)-22a. A solution of diol
81)-22a 80.50 g, 2.10 mmol) in anhydrous DMF 811 mL)
containing imidazole 80.29 g, 4.20 mmol) was treated at 08C
with TBDMS-Cl 80.32 g, 2.10 mmol) and the resulting
reaction mixture was stirred at rt for 18 h. Dilution with
ether and evaporation of the washed 8water) organic solvent
afforded a crude product 80.73 g, 99% yield) mostly consist-
ing of alcohol 81)-23, which was directly utilized in the
next step without any further puri®cation. An analytical
sample of crude 81)-23 was subjected to ¯ash chroma-
tography. Elution with a 9.5:0.5 hexane/AcOEt mixture
afforded pure ,1)-benzyl 3-,O-t-butyldimethylsilyl)-2,6-
dideoxy-a-d-glucopyranoside 823), as a liquid 8Found: C,
64.91; H, 9.28. C19H32O4Si requires C, 64.73; H, 9.15):
,1)-Benzyl3,4-di-,O-acety)-l2-, a-bromo)-2,6-dideoxy-b-
d-glucopyranoside 819), a solid, mp 93.5±958C 8recrystal-
lized from hexane/CHCl3) 8Found: C, 50.54; H, 5.01.
25
C17H21BrO6 requires C, 50.89; H, 5.28): [a]D ˆ122.4 8c
1
0.4, CHCl3). IR 1749 cm21 8CvO); H NMR d 7.30±7.45
8m, 5H), 5.24 8dd, 1H, Jˆ10.7, 9.5Hz), 4.92 8d, 1H,
Jˆ11.8 Hz), 4.68 8d, 1H, Jˆ11.8 Hz), 4.74 8t, 1H,
Jˆ9.5Hz), 4.60 8d, 1H, Jˆ8.7 Hz), 3.84 8dd, 1H, Jˆ10.7,
8.7 Hz), 3.59 8dq, 1H, Jˆ9.5, 6.2 Hz), 2.08 8s, 3H), 2.03 8s,
3H), 1.27 8d, 3H, Jˆ6.2 Hz); 13C NMR d 170.51, 170.38,
137.01, 129.07, 128.75, 101.28, 75.33, 74.87, 71.93, 70.68,
50.53, 21.30, 17.93 81£Ph and 1£Me signals unresolved).
[a]D ˆ180.158 c 1.8, CHCl3). IR 3499 cm21 8OH); H
NMR d 7.20±7.40 8m, 5H), 4.90 8unresolved dd, 1H,
Jˆ2.8 Hz), 4.68 8d, 1H, Jˆ12.2 Hz), 4.458d, 1H, Jˆ
12.2 Hz), 3.96 8ddd, 1H, Jˆ11.3, 9.0, 5.1 Hz), 3.73 8dq,
1H, Jˆ9.0, 6.2 Hz), 3.13 8td, 1H, Jˆ9.0, 2.0 Hz), 2.06
8ddd, 1H, Jˆ12.6, 5.1, 1.2 Hz), 1.70 8ddd, 1H, Jˆ12.6,
11.3, 3.7 Hz), 1.29 8d, 3H, Jˆ6.2 Hz), 0.89 8s, 9H), 0.11
8s, 3H), 0.09 8s, 3H); 13C NMR d 138.60, 129.02, 128.34,
128.23, 97.28, 78.63, 71.20, 69.26, 68.22, 39.26, 26.44,
18.56, 18.66, 23.51, 23.96.
25
1
5.1.4. Diacetate ꢀ1)-21. A solution of bromide 81)-20
85.97 g, 14.9 mmol) in anhydrous benzene 880 mL) was
treated with Bu3SnH 86.50 g, 22.3 mmol) in the presence
of a catalytic amount of benzoyl peroxide and the resulting
reaction mixture was re¯uxed for 1 h. After cooling,
evaporation of the solvent afforded a residue which was
dissolved in MeCN. Evaporation of the washed 8petroleum
ether) acetonitrile solution yielded a crude liquid product
consisting of the diacetate 81)-21 84.75g, 99% yield) prac-
tically pure which was directly utilized in the next step
without any further puri®cation. An analytical sample of
crude 81)-21 80.10 g) was puri®ed by preparative TLC
with an 85:15 hexane/AcOEt mixture as the eluant. Extrac-
tion of the most intense band afforded pure ,1)-benzyl3,4-
di-,O-acetyl)-2,6-dideoxy-a-d-glucopyranoside 821), as a
liquid 80.076 g, 76% yield) 8Found: C, 63.07; H, 6.51.
5.1.7. Mesylate ꢀ1)-24. A solution of alcohol 81)-23
80.49 g, 1.40 mmol) in anhydrous pyridine 86 mL) was
treated at 08C with MsCl 80.64 g, 5.6 mmol) and the result-
ing reaction mixture was stirred at rt for 18 h. Dilution with
ether and evaporation of the washed 8water) organic solvent
afforded a crude product 80.60 g) mostly consisting of
mesylate 81)-24 which was ®ltered through a short silica
gel column. Elution with an 85:15 hexane/AcOEt mixture
afforded pure ,1)-benzyl 3-,O-t-butyldimethylsilyl)-4-,O-
mesyl)-2,6-dideoxy-a-d-glucopyranoside 824) 80.56 g,
90% yield), as a liquid 8Found: C, 55.66; H, 7.92.
25
C17H22O6 requires C, 63.34; H, 6.88): [a]D ˆ1142.1 8c
1
0.9, CHCl3). IR 1745cm 21 8CvO); H NMR d 7.20±7.41
25
8m, 5H), 5.32 8ddd, 1H, Jˆ11.6, 9.8, 5.4 Hz), 4.96
8unresolved dd, 1H, Jˆ3.0 Hz), 4.76 8t, 1H, Jˆ9.8 Hz),
4.68 8d, 1H, Jˆ12.1 Hz), 4.48 8d, 1H, Jˆ12.1 Hz), 3.90
8dq, 1H, Jˆ9.8, 6.1 Hz), 2.27 8ddd, 1H, Jˆ12.9, 5.4,
1.2 Hz), 2.058s, 3H), 2.00 8s, 3H), 1.81 8ddd, 1H, Jˆ12.9,
11.6, 3.7 Hz), 1.17 8d, 3H, Jˆ6.1 Hz); 13C NMR d 170.86,
138.03, 129.04, 128.44, 128.38, 96.54, 75.45, 69.70, 69.57,
66.41, 35.89, 21.65, 21.48, 18.16 81£CO signal unresolved).
C20H34O6SSi requires C, 55.78; H, 7.96): [a]D ˆ165.3
8c 1.4, CHCl3); 1H NMR d 7.20±7.40 8m, 5H), 4.90
8unresolved dd, 1H, Jˆ2.6 Hz), 4.658d, 1H, Jˆ12.2 Hz),
4.46 8d, 1H, Jˆ12.2 Hz), 4.10±4.30 8m, 2H), 3.87 8dq, 1H,
Jˆ9.2, 6.3 Hz), 3.07 8s, 3H), 2.19 8ddd, 1H, Jˆ13.1, 4.6,
1.1 Hz), 1.758ddd, 1H, Jˆ13.1, 10.9, 3.6 Hz), 1.34 8d, 3H,
Jˆ6.3 Hz), 0.90 8s, 9H), 0.13 8s, 3H), 0.10 8s, 3H); 13C NMR
d 138.24, 129.10, 128.40, 128.32, 96.67, 87.10, 69.58,

6080
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
68.50, 66.96, 40.32, 39.70, 26.57, 18.70, 23.16, 23.77
81£Me signals unresolved).
7.20±7.42 8m, 7H), 4.86 8dd, 1H, Jˆ3.4, 1.2 Hz), 4.80
8ddd, 1H, Jˆ11.6, 9.0, 5.4 Hz), 4.63 8d, 1H, Jˆ12.1 Hz),
4.41 8d, 1H, Jˆ12.1 Hz), 3.72 8dq, 1H, Jˆ9.1, 6.2 Hz), 3.32
8t, 1H, Jˆ9.1 Hz), 2.458s, 3H), 2.11 8ddd, 1H, Jˆ12.8, 5.4,
1.2 Hz), 1.83 8ddd, 1H, Jˆ12.8, 11.6, 3.6 Hz), 1.29 8d, 3H,
Jˆ6.2 Hz); 13C NMR d 145.77, 138.00, 134.03, 130.59,
129.05, 128.57, 128.39, 96.42, 81.39, 75.27, 69.41, 68.47,
36.61, 22.37, 18.46 81£Ph signal unresolved).
5.1.8. Hydroxy mesylate ꢀ1)-25. A solution of mesylate
81)-24 80.47 g, 1.06 mmol) in anhydrous THF 815mL) was
treated at 08C with 1 M TBAF in THF 82.2 mL, 2.20 mmol)
and the resulting reaction mixture was stirred at the same
temperature for 20 min. Dilution with ether and evaporation
of the washed 8water) organic solvent afforded a crude
product 80.40 g) mostly consisting of hydroxy mesylate
81)-25 which was subjected to ¯ash chromatography.
Elution with a 70:30 hexane/AcOEt mixture afforded pure
,1)-benzyl4-,O-mes)y-l2,6-dideoxy- a-d-glucopyranoside
825) 80.24 g, 72% yield), as a solid, mp 64.5±668C 8recrys-
tallized from hexane/AcOEt) 8Found: C, 53.39; H, 6.02.
,1)-Benzyl4-,O-tos)y-2l ,6-dideoxy- a-d-glucopyranoside
827), a liquid 8Found: C, 61.34; H, 6.21. C20H24O6S requires
25
C, 61.21; H, 6.16): [a]D ˆ183.2 8c 2.4, CHCl3). IR
3489 cm21 8OH); 1H NMR d 7.84 8d, 2H, Jˆ8.4 Hz),
7.20±7.458m, 7H), 4.93 8unresolved dd, 1H, Jˆ3.2 Hz),
4.61 8d, 1H, Jˆ11.9 Hz), 4.42 8d, 1H, Jˆ11.9 Hz), 4.08±
4.26 8m, 2H), 3.79 8dq, 1H, Jˆ9.4, 6.1 Hz), 2.458s, 3H),
2.26 8ddd, 1H, Jˆ13.3, 4.8, 1.1 Hz), 1.74 8ddd, 1H, Jˆ13.3,
11.3, 3.7 Hz), 1.12 8d, 3H, Jˆ6.1 Hz); 13C NMR d 146.06,
138.02, 133.75, 130.59, 129.10, 128.68, 128.47, 128.41,
96.79, 87.54, 69.76, 67.39, 65.69, 38.11, 22.37, 18.22.
25
C14H20O6S requires C, 53.15; H, 6.37): [a]D ˆ1110.2 8c
1.0, CHCl3). IR 3450 cm21 8OH); 1H NMR d 7.20±7.40 8m,
5H), 4.95 8unresolved dd, 1H, Jˆ2.9 Hz), 4.658d, 1H,
Jˆ11.9 Hz), 4.458d, 1H, Jˆ11.9 Hz), 4.10±4.30 8m, 2H),
3.94 8dq, 1H, Jˆ9.1, 6.2 Hz), 3.158s, 3H), 2.28 8ddd, 1H,
Jˆ13.1, 5.0, 1.2 Hz), 1.75 8ddd, 1H, Jˆ13.1, 11.1, 3.6 Hz),
1.32 8d, 3H, Jˆ6.2 Hz); 13C NMR d 137.97, 129.16, 128.51,
96.75, 86.80, 69.83, 67.57, 66.01, 39.28, 38.89, 18.34 81£Ph
signal unresolved).
,1)-Benzyl3,4-di-,O-tosy)l-2,6-dideoxy- a-d-glucopyrano-
side 828), a liquid 8Found: C, 59.03; H, 5.27. C27H30O8S2
25
requires C, 59.32; H, 5.53): [a]D ˆ186.0 8c 1.9, CHCl3);
1H NMR d 7.80 8d, 2H, Jˆ8.4 Hz), 7.62 8d, 2H, Jˆ8.4 Hz),
7.20±7.42 8m, 9H), 4.71±4.90 8m, 2H), 4.57 8d, 1H,
Jˆ12.0 Hz), 4.40 8d, 1H, Jˆ12.0 Hz), 4.43 8t, 1H,
Jˆ9.4 Hz), 3.82 8dq, 1H, Jˆ9.4, 6.3 Hz), 2.458s, 3H),
2.43 8s, 3H), 2.22 8ddd, 1H, Jˆ13.1, 5.3, 1.3 Hz), 1.83
8ddd, 1H, Jˆ13.1, 11.8, 3.4 Hz), 1.22 8d, 3H, Jˆ6.3 Hz);
13C NMR d 145.64, 145.59, 137.75, 134.55, 134.03, 130.42,
129.10, 128.78, 128.54, 128.35, 96.06, 81.86, 76.48, 69.69,
67.00, 37.17, 22.40, 18.54 82£Ph and 1£Me signals
unresolved).
5.1.9. Epoxide ꢀ1)-3. A solution of hydroxy mesylate 81)-
25 80.24 g, 0.76 mmol) in anhydrous toluene 810 mL) was
treated with Amberlyst IRA-400 8OH2) 80.24 g) and the
resulting suspension was stirred at rt for 1 h. Evaporation
of the ®ltered organic solution afforded pure ,1)-benzyl3,4-
anhydro-2,6-dideoxy-a-d-galactopyranoside 83) 80.164 g,
98% yield), as a solid, mp 31±348C 8recrystallized from
hexane) 8Found: C, 70.55; H, 7.28. C13H16O3 requires C,
25
1
70.89; H, 7.32): [a]D ˆ1110.8 8c 0.5, CHCl3); H NMR
d 7.20±7.40 8m, 5H), 4.81 8d, 1H, Jˆ5.0 Hz), 4.69 8d, 1H,
Jˆ11.9 Hz), 4.47 8d, 1H, Jˆ11.9 Hz), 4.158q, 1H, Jˆ
6.7 Hz), 3.34 8t, 1H, Jˆ4.4 Hz), 3.058d, 1H, Jˆ4.4 Hz),
2.16 8dd, 1H, Jˆ15.7, 5.0 Hz), 1.98 8ddd, 1H, Jˆ15.7,
5.0, 1.0 Hz), 1.36 8d, 3H, Jˆ6.7 Hz); 13C NMR d 138.17,
129.11, 128.52, 128.47, 94.16, 69.69, 61.94, 53.47, 49.39,
29.04, 18.27.
5.1.11. Epoxide ꢀ1)-4. A solution of the 73:17:10 mixture
of monotosylates 81)-26 and 81)-27 and ditosylate 81)-28
81.42 g), in anhydrous benzene 840 mL) was treated at rt
with Amberlyst IRA-400 8OH2) 81.40 g) and the reaction
suspension was stirred at the same temperature for 1 h.
Evaporation of the ®ltered organic solution afforded a
crude product 80.80 g) consisting of a 73:17:10 mixture of
epoxides 81)-4 and 81)-3 and ditosylate 81)-28 which was
subjected to ¯ash chromatography. Elution with an 85:15
hexane/AcOEt mixture afforded pure epoxide 81)-3 80.11 g,
15% yield), ditosylate 81)-28 80.071 g) and ,1)-benzyl3,4-
anhydro-2,6-dideoxy-a-d-allopyranoside 84), as a liquid
80.40 g, 55% yield) 8Found: C, 70.65; H, 7.06. C13H16O3
5.1.10. Monotosylation of diol ꢀ1)-22a. A solution of diol
81)-22a 81.19 g, 5.0 mmol) in anhydrous pyridine 825 mL)
was treated at 08C with TsCl 81.01 g, 5.30 mmol) and the
resulting reaction mixture was stirred at rt for 5days.
Dilution with ether and evaporation of the washed 8water)
organic solvent afforded a crude residue 81.87 g) consisting
of a 73:17:10 mixture of monotosylates 81)-26 and 81)-27
881% yield) and ditosylate 81)-28 which was directly used
in the next step without any further puri®cation. An
analytical sample 80.35g) of this mixture was subjected to
preparative TLC using an 1:1 petroleum ether/Et2O mixture
as the eluant. Extration of the three most intense bands 8the
fastest and slowest moving bands contained 28 and 27,
respectively) afforded pure monotosylates 81)-26
80.182 g) and 81)-27 80.041 g), and ditosylate 81)-28
80.020 g).
25
requires C, 70.89; H, 7.32): [a]D ˆ1136.3 8c 1.6,
1
CHCl3); H NMR d 7.20±7.42 8m, 5H), 4.78 8dd, 1H,
Jˆ4.7, 3.0 Hz), 4.72 8d, 1H, Jˆ12.3 Hz), 4.46 8d, 1H,
Jˆ12.3 Hz), 4.21 8q, 1H, Jˆ7.0 Hz), 3.21±3.30 8m, 1H),
3.00 8dd, 1H, Jˆ4.4 Hz), 2.00±2.24 8m, 2H), 1.38 8d, 3H,
Jˆ7.0 Hz); 13C NMR d 138.28, 128.96, 128.55, 128.22,
93.51, 69.86, 65.29, 54.29, 48.95, 29.83, 19.34.
5.1.12. Hydrogenolysis of dichloro diol ꢀ1)-30a. Follow-
ing a previously described procedure,9a a solution of
dichloro diol 81)-30a 82.0 g, 8.66 mmol) in anhydrous
EtOH 820 mL) containing KOH 81.80 g, 32.14 mmol) was
stirred at rt under an hydrogen atmosphere in the presence of
Ni-Raney 89.20 g) for 24 h. Evaporation of the ®ltered
8Celite) and neutralized 8aqueous 10% HCl) organic
,1)-Benzyl3-,O-tos)y-2l,6-dideoxy- a-d-glucopyranoside
826), a liquid 8Found: C, 61.56; H, 6.05. C20H24O6S requires
25
C, 61.21; H, 6.16): [a]D ˆ1107.7 8c 1.0, CHCl3). IR
3524 cm21 8OH); 1H NMR d 7.82 8d, 2H, Jˆ8.3 Hz),

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6081
solution afforded a crude product which was taken up in
boiling CHCl3. Evaporation of the ®ltered organic solution
afforded a crude product 81.40 g) consisting of a 9:1 mixture
of diol 81)-31a and oxabicyclic compound 81)-33 which
was subjected to ¯ash chromatography. Elution with a 7:3
CH2Cl2/acetone mixture afforded pure diol 81)-31a 81.12 g,
80% yield) and the oxabicyclic compound 81)-33 80.13 g,
9% yield).
aqueous NaHCO3 and NaCl) organic solution afforded a
crude product consisting of mesylate 81)-35a 80.114 g)
which was subjected to ¯ash chromatography. Elution
with an 1:1 hexane/AcOEt mixture afforded pure ,1)-
methyl 2-,O-acetyl)-3-,O-mesyl)-4,6-dideoxy-a-d-gluco-
pyranoside 835a) 80.092 g, 77% yield), as a solid, mp 56±
598C 8recrystallized from hexane/CH2Cl2) 8Found: C,
42.84; H, 6.66. C10H18O7S requires C, 42.55; H, 6.43):
25
[a]D ˆ1138.0 8c 1.0, CHCl3). IR 1748 cm218CO); 1H
,1)-Methyl4,6-dideoxy- a-d-glucopyranoside 831a),9
a
NMR d 4.958ddd, 1H, Jˆ11.4, 10.0, 5.2 Hz), 4.86 8d, 1H,
Jˆ3.5Hz), 4.76 8dd, 1H, Jˆ10.0, 3.5Hz), 3.90 8dqd, 1H,
Jˆ11.4, 6.3, 2.2 Hz), 3.30 8s, 3H), 2.96 8s, 3H), 2.24 8ddd,
1H, Jˆ12.7, 5.2, 2.3 Hz), 2.06 8s, 3H), 1.65 8dt, 1H, Jˆ12.7,
11.4 Hz), 1.17 8d, 3H, Jˆ6.3 Hz); 13C NMR d 170.67,
98.11, 76.39, 72.64, 63.55, 55.77, 40.38, 38.96, 21.55,
21.11.
25
solid, mp 106±1078C, [a]D 23ˆ1178.3 8c 1.6, MeOH)
[lit.9b,c mp 107±1098C, [a]D ˆ1171 8c 1.0, MeOH);9a
mp 106±1078C, [a]D ˆ1178.58 c 0.9, MeOH)9b].
24
,1)-Methyl4-deoxy-3,6-anhydro-
a-d-glucopyranoside
833), a solid, mp 95±968C 8recrystallized from hexane/
Et2O) 8Found: C, 52.41; H, 7.86. C7H12O4 requires C,
25
52.49; H, 7.55): [a]D ˆ1109.0 8c 3.6, CHCl3). IR
5.1.16. Epoxide ꢀ1)-8. A solution of mesylate 81)-35a
80.23 g, 0.81 mmol) in MeOH 85mL) was treated at rt
under stirring with MeONa 80.020 g). After 2 h stirring,
evaporation of the neutralized 810% aqueous HCl) organic
solvent afforded a crude reaction product 80.19 g) consisting
of hydroxy mesylate 36a [IR 3468 cm21 8OH)]11b which
was dissolved in anhydrous benzene 87 mL) and treated
under stirring with t-BuOK 80.18 g, 1.60 mmol). After
30 min stirring ar rt, evaporation of the ®ltered organic
solution afforded pure ,1)-methyl2,3-anhydro-4,6-
dideoxy-a-d-allopyranoside 88)9b,11 80.076 g, 65% yield),
3460 cm21 8OH); 1H NMR d 4.73 8d, 1H, Jˆ2.8 Hz),
4.47±4.57 8m, 2H), 4.09 8dd, 1H, Jˆ10.0, 1.2 Hz), 3.79
8dd, 1H, Jˆ10.0, 2.8 Hz), 3.60±3.80 8m, 1H), 3.55 8s,
3H), 2.53 8dt, 1H, Jˆ12.2, 1.3 Hz), 1.61 8ddd, 1H, Jˆ
12.2, 5.9, 2.6 Hz); 13C NMR d 98.14, 77.09, 74.66, 72.00,
69.02, 57.46, 31.70.
5.1.13. Reaction of the dichloro diol ꢀ1)-30a with
a
Bu3SnH. Following a previously described procedure,9c
solution of dichloro diol 81)-30a 80.70 g, 3.03 mmol) in
anhydrous toluene 814 mL) was treated with Bu3SnH
83.62 g, 12.4 mmol) in the presence of a catalytic amount
of AIBN and the resulting reaction mixture was re¯uxed for
18 h. After cooling, evaporation of the solvent afforded an
oily residue which solidi®ed on treatment with petroleum
ether. Filtration gave a solid consisting of an almost 1:1
mixture of diol 81)-31a and monochloro derivative 32:9e
1H NMR d 4.83 8d, 1H, Jˆ3.8 Hz), 3.56 8d, 2H, Jˆ
5.4 Hz), 3.44 8s, 3H), 2.10 8ddd, 1H, Jˆ12.6, 5.0, 2.1 Hz),
1.50 8unresolved dt, 1H, Jˆ12.3, 11.7 Hz).
25
24
as a liquid, [a]D ˆ172 8c 1.0, CHCl3) [lit.9b,11a,b [a]D
ˆ
1758 c 1.0, CHCl3);9b [a]D ˆ166.8 8c 1.2, CHCl3);11a
18
23
[a]D ˆ177 8c 1.3, CHCl3)11b].
5.1.17. Reaction of diol ꢀ1)-31a with PPh3-DEAD. A
solution of diol 81)-31a 81.46 g, 9.0 mmol) in anhydrous
Ê
benzene 845mL) containing 4 A molecular sieves was
treated under stirring with PPh3 82.59 g, 9.90 mmol) and
DEAD 81.72 g, 9.90 mmol). After precipitation of white
needles had occured, the reaction mixture was re¯uxed for
24 h, then cooled and evaporated to afford a crude
residue which was taken up with Et2O. Evaporation of
the ®ltered organic solution afforded a liquid product
which was distilled 8KuÈgel±Rohr) to give pure epoxide
81)-8 80.80 g, 62% yield), as a liquid, bp 1308C
813 mmHg).9b,11
5.1.14. Monoacetate ꢀ1)-34a. A solution of diol 81)-31a
80.10 g, 0.62 mmol) in a 7:3 mixture of vinyl acetate and
THF 816 mL) was treated at 378C with lipase PS immobi-
lized on Hy¯o Super Cell 80.62 g). After 24 h stirring at the
same temperature, evaporation of the solvent afforded a
crude reaction product consisting of monoacetate 81)-34a
80.12 g) which was subjected to ¯ash chromatography.
Elution with an 8:2 CH2Cl2/acetone mixture afforded pure
,1)-methyl2-,O-acety)l-4,6-dideoxy- a-d-glucopyranoside
834a), as a liquid 80.088 g, 70% yield) 8Found: C, 52.60;
H, 7.71. C9H16O5 requires C, 52.93; H, 7.90): aˆ1154.0 8c
1.6, CHCl3). IR 3471 8OH) and 1740 cm21 8CO); 1H NMR d
4.80 8d, 1H, Jˆ3.6 Hz), 4.55 8dd, 1H, Jˆ9.8, 3.6 Hz), 4.02
8ddd, 1H, Jˆ11.6, 9.8, 5.4 Hz), 3.86 8dqd, 1H, Jˆ11.6, 6.3,
2.5Hz), 3.29 8s, 3H), 2.08 8s, 3H), 1.99 8ddd, 1H, Jˆ12.7,
5.4, 2.5 Hz), 1.38 8dt, 1H, Jˆ12.7, 11.6 Hz), 1.158d, 3H,
Jˆ6.3 Hz); 13C NMR d 171.93, 98.17, 76.86, 66.41, 64.21,
55.64, 41.57, 21.70, 21.36.
5.1.18. Epoxide ꢀ1)-7. A solution of diol 81)-31a 81.06 g,
6.54 mmol) in anhydrous pyridine 820 mL) was treated at rt
under stirring with TsCl 81.49 g, 7.83 mmol). After 4 days
stirring at the same temperature, dilution with CH2Cl2 and
evaporation of the washed 8water) organic solution afforded
a crude oily residue consisting of an 85:15 mixture of mono-
tosylates 37 and 38 81.96 g, 95% yield) which was dissolved
in anhydrous benzene 840 mL) and treated at rt with t-BuOK
81.10 g, 9.81 mmol). After 2 h stirring at the same tempera-
ture, evaporation of the ®ltered organic solution afforded a
crude product 80.72 g) consisting of an 80:20 mixture of
epoxides 81)-7 and 81)-8, which was subjected to ¯ash
chromatography. Elution with an 8:2 hexane/AcOEt
mixture afforded pure epoxide 81)-8 80.090 g, 9% yield)
and ,1)-methyl2,3-anhydro-4,6-dideoxy- a-d-mannopyra-
5.1.15. Mesylate ꢀ1)-35a. A solution of acetate 81)-34a
80.086 g, 0.42 mmol) in anhydrous pyridine 83.0 mL) was
treated at 08C, under stirring, with MsCl 80.096 g,
0.84 mmol). After 18 h at the same temperature, dilution
with CH2Cl2 and evaporation of the washed 8saturated
noside 87)9b,11b 80.55 g, 58% yield), as
a liquid,
25
25
[a]D ˆ15 2 c8 1.0, CHCl3) [lit.9b,11b [a]D ˆ155 8c 2.7,
CHCl3);9b [a]D ˆ15 2 8c 1.4, CHCl3)11b].
23

6082
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
5.1.19. Diacetate ꢀ1)-39a. A solution of diol 81)-31a
81.0 g, 6.17 mmol) in anhydrous pyridine 820 mL) was
treated with Ac2O 84 mL) and the reaction mixture was
stirred at rt for 24 h. Evaporation of the organic solvent
afforded the diacetate 81)-39a 81.35g, 89% yield),
practically pure as a liquid, which was directly used in the
next step without any further puri®cation. An analytical
sample was subjected to preparative TLC with an 8:2
CH2Cl2/MeCN mixture. Extraction of the most intense
band afforded pure ,1)-methyl2,3-di-,O-acet)y-l4,6-
5.1.23. Monoacetate ꢀ1)-40b. Proceeding as previously
described for the corresponding reaction of diol 81)-31a
the treatment of a solution of diol 82)-31b 80.663 g,
4.09 mmol) in a 7:3 mixture of vinyl acetate and THF
8100 mL) with lipase PS immobilized on Hy¯o Super Cell
84.0 g) at 378C under stirring for 24 h afforded a crude
reaction product consisting of monoacetate 81)-40b
80.83 g, 99% yield) which was directly utilized in the next
step. An analytical sample 80.080 g) was subjected to
preparative TLC with an 8:2 CH2Cl2/CH3CN mixture as
the eluant. Extraction of the most intense band afforded
pure ,1)-methyl3-,O-acety)l-4,6-dideoxy- b-d-glucopyra-
noside 840b) 80.064 g), as a liquid 8Found: C, 52.77; H,
dideoxy-a-d-glucopyranoside 839a),16a as
a
liquid,
25
[a]D ˆ1163.58 c 2.4, MeOH).
25
5.1.20. Reaction of diacetate ꢀ1)-39a with lipase PPL. A
solution of diacetate 81)-39a 80.093 g, 0.38 mmol) in
acetone 83 mL) and phosphate buffer 8pH 7, 30 mL) was
treated with crude lipase PPL type II immobilized on
Hy¯o Super Cell 80.50 g) and the reaction mixture was
incubated, under stirring, at 378C. When TLC analysis
showed that all the starting material was consumed,
evaporation of the ®ltered organic solvent afforded a
crude oily product 80.077 g) consisting of a 60:40 mixture
of hydroxy acetates 40a and 34a which was subjected to
¯ash chromatography. Elution with an 1:1 hexane/AcOEt
mixture afforded pure hydroxy acetates 81)-34a 80.024 g,
31% yield) and methyl3-,O-acetyl)-4,6-dideoxy- a-d-gluco-
pyranoside 840a) 80.036 g, 46% yield), as a liquid 8Found:
C, 52.72; H, 7.98. C9H16O5 requires C, 52.93; H, 7.90). IR
3466 8OH) and 1738 cm21 8CO); 1H NMR d 4.99 8ddd, 1H,
Jˆ11.6, 9.8, 5.0 Hz), 4.71 8d, 1H, Jˆ3.8 Hz), 3.88 8dqd, 1H,
Jˆ11.6, 6.3, 2.0 Hz), 3.44±3.56 8m, 1H), 3.35 8s, 3H), 2.03
8s, 3H), 1.97 8ddd, 1H, Jˆ12.7, 5.0, 2.0 Hz), 1.32 8dt, 1H,
Jˆ12.7, 11.6 Hz), 1.14 8d, 3H, Jˆ6.3 Hz); 13C NMR d 171.84,
100.72, 72.30, 72.07, 64.29, 55.89, 38.54, 21.91, 21.35.
7.66. C9H16O5 requires C, 52.93; H, 7.90): [a]D ˆ18.2
1
8c 1.2, CHCl3). IR 3460 8OH) and 1736 cm21 8CO); H
NMR d 4.86 8ddd, 1H, Jˆ11.4, 9.3, 5.2 Hz), 4.18 8d, 1H,
Jˆ7.8 Hz), 3.658dqd, 1H, Jˆ11.4, 6.2, 1.9 Hz), 3.43 8dd,
1H, Jˆ9.3, 7.8 Hz), 3.56 8s, 3H), 2.10 8s, 3H), 2.04±2.18
8m, 1H), 1.41 8dt, 1H, Jˆ12.7, 11.4 Hz), 1.27 8d, 3H,
Jˆ6.2 Hz); 13C NMR d 171.58, 104.52, 73.66, 73.53,
68.38, 57.60, 38.35, 21.71, 21.27.
5.1.24. Mesylate ꢀ2)-43b. A solution of acetate 81)-40b
80.83 g, 4.07 mmol) in anhydrous pyridine 820 mL) was
treated at 08C under stirring with MsCl 81.83 g,
16.0 mmol) and the reaction mixture was stirred at rt for
3 h. Dilution with ice-water and CH2Cl2 and evaporation
of the washed 8water) organic solvent afforded a crude
solid residue 81.10 g) which was recrystallized from hexane/
AcOEt to give pure ,2)-methyl 3-,O-acetyl)-2-,O-mesyl)-
4,6-dideoxy-b-d-glucopyranoside 843b) 80.79 g, 69%
yield), as a solid mp 76±79.58C 8Found: C, 42.79; H,
25
6.24. C10H18O7S requires C, 42.55; H, 6.43): [a]D
ˆ
218.1 8c 1.0, CHCl3). IR 1741 cm21 8CO); H NMR d
4.30±4.458m, 2H), 4.93±.512 8m, 1H), 3.67 8dqd, 1H,
Jˆ11.6, 6.2, 1.9 Hz), 3.55 8s, 3H), 3.07 8s, 3H), 2.16 8ddd,
1H, Jˆ13.0, 5.4, 1.9 Hz), 2.11 8s, 3H), 1.51 8dt, 1H, Jˆ13.0,
11.6 Hz), 1.29 8d, 3H, Jˆ6.2 Hz); 13C NMR d 171.00,
101.84, 81.30, 70.83, 68.61, 57.46, 39.55, 38.72, 21.60,
21.11.
1
5.1.21. Diacetate ꢀ1)-39b. A solution of diacetate 81)-39a
82.46 g, 10.0 mmol) in anhydrous toluene 895mL) was trea-
ted at rt under stirring with 8CH3)3SiI 85.7 mL, 40.0 mmol)
and the reaction mixture was stirred at the same temperature
for 24 h. Dilution with CHCl3 and evaporation of the
washed 8water, 10% aqueous Na2S2O3 and saturated
aqueous NaHCO3) organic solution, afforded a crude resi-
due which was immediately dissolved in MeOH 8200 mL),
treated with Ag2CO3 83.58 g, 12.98 mmol) and the reaction
mixture was gently re¯uxed for 4 h. After cooling, evapora-
tion of the ®ltered 8Celite) organic solvent afforded a crude
liquid product consisting of the diacetate 81)-39b16b
82.40 g, 97% yield) which was directly utilized in the next
step. An analytical sample was subjected to preparative
TLC with an 8:2 CH2Cl2/MeCN mixture as the eluant.
Extraction of the most intense band afforded pure ,1)-
methyl2,3-di-,O-acety)l-4,6-dideoxy- b-d-glucopyranoside
5.1.25. Hydroxy mesylate ꢀ2)-44b. A solution of mesylate
82)-43b 80.56 g, 2.0 mmol) in MeOH 820 mL) was treated
with MeONa 80.020 g) and the reaction mixture was stirred
1 h at rt. Evaporation of the neutralized 810% aqueous HCl)
organic solution afforded a crude solid reaction product
80.44 g) which was recrystallized from hexane/AcOEt to
give pure ,2)-methyl2-,O-mesy)l-4,6-dideoxy- b-d-gluco-
pyranoside 844b) 80.33 g, 69% yield), as a solid, mp 96±
988C 8Found: C, 40.31; H, 6.38. C8H16O6S requires C,
25
39.99; H, 6.71): [a]D ˆ248.8 8c 3.0, CHCl3). IR
1
3465cm 218OH); H NMR d 4.30 8d, 1H, Jˆ7.9 Hz), 4.15
839b), as a liquid, [a]D ˆ110.58 c 0.4, dioxane) [lit.16b
8dd, 1H, Jˆ8.9, 7.9 Hz), 3.78 8ddd, 1H, Jˆ11.5, 8.9,
5.3 Hz), 3.62 8dqd, 1H, Jˆ11.5, 6.2, 1.9 Hz), 3.54 8s, 3H),
3.14 8s, 3H), 2.10 8ddd, 1H, Jˆ13.2, 5.3, 1.9 Hz), 1.50 8dt,
1H, Jˆ13.2, 11.5Hz), 1.29 8d, 3H, Jˆ6.2 Hz); 13C NMR d
101.54, 85.57, 69.89, 68.71, 57.43, 41.11, 39.12, 21.18.
25
25
[a]D ˆ111.3 8c 0.3, dioxane)].
5.1.22. Diol ꢀ2)-31b. A solution of diacetate 81)-39b
82.46 g, 10.0 mmol) in MeOH 850 mL) was treated with
MeONa 80.15g). After 1 h stirring at rt, the solution was
neutralized 810% aqueous HCl) and evaporated to give ,2)-
methyl4,6-dideoxy- b-d-glucopyranoside 831b)19 81.35g,
5.1.26. Epoxide ꢀ2)-5. A solution of hydroxy mesylate
82)-44b 80.26 g, 1.08 mmol) in anhydrous benzene
86 mL) was treated with t-BuOK 80.24 g, 2.16 mmol) and
the reaction mixture was stirred at rt for 30 min. Evapora-
tion of the ®ltered organic solution afforded pure ,2)-methyl
25
83% yield), as a solid, mp 100±1028C, [a]D ˆ259.7 8c
1.2, CHCl3) 8lit.19 mp 104±1058C, [a]D ˆ260.4 8c 1.2,
20
CHCl3).

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6083
2,3-anhydro-4,6-dideoxy-b-d-mannopyranoside
85)21
80.143 g, 92% yield), as a liquid 8Found: C, 58.63; H,
1H, Jˆ12.9, 4.6, 2.0 Hz), 1.33 8dt, 1H, Jˆ12.9, 11.7 Hz),
1.20 8d, 3H, Jˆ6.2 Hz); 13C NMR: d 139.11, 129.15,
128.42, 104.51, 78.87, 75.66, 72.26, 68.73, 57.59, 38.64,
21.63 81£Ph signal unresolved).
25
8.70. C7H12O3 requires C, 58.32; H, 8.39): [a]D ˆ295.2
8c 1.7, CHCl3); 1H NMR d 4.70 8s, 1H), 3.40±3.60 8m, 1H),
3.49 8s, 3H), 3.26 8td, 1H, Jˆ4.5, 0.9 Hz), 3.02 8d, 1H,
Jˆ4.5Hz), 1.79 8dt, 1H, Jˆ15.2, 4.8 Hz), 1.66 8unresolved
ddd, 1H, Jˆ15.2, 10.8 Hz), 1.13 8d, 3H, Jˆ6.1 Hz); 13C
NMR d 99.49, 69.45, 56.98, 51.81, 50.34, 30.84, 21.43.
1
8^)-50a: H NMR d 4.70 8d, 1H, Jˆ3.5Hz), 1.14 8d, 3H,
Jˆ6.3 Hz).
5.1.30. Acetates ꢀ^)-51a and ꢀ^)-51b. A solution of the
9:1 mixture of alcohols 8^)-50b and 8^)-50a 80.177 g,
0.70 mmol) in anhydrous pyridine 83 mL) was treated
under stirring at rt with Ac2O 80.5mL). After 1 h, the
usual treatment afforded a crude product consisting of a
9:1 mixture of acetates 8^)-51b and 8^)-51a 80.19 g,
92% yield), which was directly utilized in the next step.
5.1.27. Epoxide ꢀ2)-6. Proceeding as previously described
for the corresponding reaction of diol 81)-31a, the treat-
ment of a solution of diol 82)-31b 80.116 g, 0.716 mmol) in
Ê
anhydrous benzene 83 mL) containing 4 A molecular sieves
with PPh3 80.213 g, 0.81 mmol) and DEAD 80.14 g,
0.81 mmol) afforded a crude liquid product which was
distilled 8KuÈgel±Rohr) to give pure ,2)-methyl2,3-anhy-
dro-4,6-dideoxy-b-d-allopyranoside 86)21 80.032 g, 31%
yield), as a liquid, bp 1308C 813 mmHg) 8Found: C,
58.51; H, 8.14. C7H12O3 requires C, 58.32; H, 8.39):
1
8^)-51b, a liquid. IR 1745cm 21 8CO); H NMR d 7.16±
7.32 8m, 5H), 4.80 8dd, 1H, Jˆ9.3, 8.0 Hz), 4.57 8d, 1H,
Jˆ12.2 Hz), 4.41 8d, 1H, Jˆ12.2 Hz), 4.158d, 1H,
Jˆ8.0 Hz), 3.32±3.58 8m, 2H), 3.39 8s, 3H), 2.02 8ddd,
1H, Jˆ12.9, 5.3, 1.7 Hz), 2.00 8s, 3H), 1.41 8dt, 1H,
Jˆ12.9, 11.5Hz), 1.22 8d, 3H, Jˆ6.2 Hz); 13C NMR d
170.53, 139.96, 129.03, 128.31, 128.10, 102.55, 77.08,
74.62, 71.62, 68.62, 57.01, 38.76, 21.78, 21.55.
25
1
[a]D ˆ283.0 8c 0.9, CHCl3); H NMR d 4.61 8s, 1H),
3.48 8s, 3H), 3.36±3.52 8m, 1H), 3.24±3.31 8m, 1H), 3.06
8d, 1H, Jˆ4.0 Hz), 1.97 8dt, 1H, Jˆ14.7, 2.4 Hz), 1.63 8ddd,
1H, Jˆ14.7, 10.8, 1.7 Hz), 1.12 8d, 3H, Jˆ6.3 Hz); 13C
NMR d 99.63, 63.02, 57.18, 54.01, 52.07, 33.10, 21.46.
5.1.28. Glycal ꢀ^)-48. A suspension of NaH 82.0 g of a 60%
dispersion in mineral oil, 50.0 mmol) in anhydrous DMF
820 mL) was treated at 08C under stirring with a solution
of alcohol 8^)-4723 82.92 g, 24.96 mmol) in anhydrous
DMF 846 mL). The reaction mixture was stirred for 1 h at
rt, then, after cooling at 08C, BnBr 84.28 g, 25.0 mmol) was
added and the reaction mixture was stirred at rt for 24 h.
After cooling at 08C, ice was added and the reaction mixture
was extracted with ether. Evaporation of the washed 8water)
organic extracts afforded a crude product 84.80 g) consisting
of benzyl derivative 48 which was subjected to ¯ash chro-
matography. Elution with an 1:1 hexane/CH2Cl2 mixture
afforded pure ,^)-cis-4-benzyloxy-3,4-dihydro-2-methyl-
2H-pyran 848) 82.50 g, 49% yield) 8Found: C, 76.21; H,
5.1.31. Hydroxy acetate ꢀ^)-34b. A solution of the 9:1
mixture of acetates 8^)-51b and 8^)-51a 80.22 g,
0.75mmol) in MeOH 83 mL) was stirred under a hydrogen
atmosphere in the presence of Pd/C 80.020 g). After 24 h,
evaporation of the ®ltered organic solution afforded a crude
product consisting of ,^)-methyl2-,O-acety)l-4,6-dideoxy-
b-d-glucopyranoside 834b) 80.13 g, 85% yield), as a liquid
8Found: C, 52.81; H, 7.64. C9H16O5 requires C, 52.93; H,
7.90). IR 1746 cm21 8CO); 1H NMR d 4.53 8dd, 1H, Jˆ9.3,
7.9 Hz), 4.17 8d, 1H, Jˆ7.9 Hz), 3.66 8ddd, 1H, Jˆ11.5, 9.3,
5.2 Hz), 3.52 8dqd, 1H, Jˆ11.5, 6.2, 1.9 Hz), 3.40 8s, 3H),
2.06 8s, 3H), 1.98 8ddd, 1H, Jˆ13.0, 5.2, 1.9 Hz), 1.40 8dt,
1H, Jˆ13.0, 11.5Hz), 1.21 8d, 3H, Jˆ6.2 Hz); 13C NMR d
170.06, 102.18, 77.08, 70.64, 68.54, 57.07, 41.59, 21.67,
21.26.
1
8.10. C13H16O2 requires C, 76.44; H, 7.90); H NMR d
7.04±7.34 8m, 5H), 6.30 8dd, 1H, Jˆ6.3, 1.9 Hz), 4.76 8dt,
1H, Jˆ6.3, 1.9 Hz), 4.46 8s, 2H), 4.13 8ddt, 1H, Jˆ9.2, 6.5,
1.9 Hz), 3.958dqd, 1H, Jˆ11.1, 6.4, 1.9 Hz), 2.058ddt, 1H,
Jˆ13.0, 6.3, 1.9 Hz), 1.63 8ddd, 1H, Jˆ13.0, 11.2, 9.2 Hz),
1.22 8d, 3H, Jˆ6.4 Hz); 13C NMR d 146.08, 139.24, 128.96,
128.17, 128.08, 103.00, 71.64, 70.36, 70.05, 36.78, 21.59.
5.1.32. Mesylate ꢀ^)-35b. A solution of hydroxy acetate
8^)-34b 80.13 g, 0.64 mmol) in anhydrous pyridine 84 mL)
was treated under stirring at 08C with MsCl 82.96 g,
2.56 mmol). After 18 h stirring at rt, dilution with CH2Cl2
and evaporation of the washed 8saturated aqueous NaHCO3
and NaCl) organic solution afforded a crude solid product
80.18 g) which was recrystallized fom hexane/acetone
to give pure ,^)-methyl2-,O-acet)y-l3-,O-mes)y-l4,6-
dideoxy-b-d-glucopyranoside 835b), as a solid, mp 108±
1108C 80.13 g, 72% yield) 8Found: C, 42.21; H, 6.18.
C10H18O7S requires C, 42.55; H, 6.43). IR 1747 cm21
5.1.29. Reaction of glycal ꢀ^)-48 with DMDO. A solution
of glycal 8^)-48 80.30 g, 1.47 mmol) in MeOH 820 mL) was
treated under stirring at 08C with solid NaHCO3 80.37 g,
4.41 mmol), oxonew 80.90 g, 1.47 mmol), a catalytic
amount of EDTA and acetone 81.6 mL). After 2 days stir-
ring at the same temperature, evaporation of the ®ltered
organic solvent afforded a residue which was taken up
with Et2O. Evaporation of the washed 810% aqueous
Na2S2O3) organic solution afforded a crude reaction product
consisting of a 9:1 mixture of glycosides 8^)-50b and 8^)-
50a 80.29 g, 78% yield) which turned out to be not separ-
able under any chromatographic conditions tried.
1
8CO); H NMR d 4.858dd, 1H, Jˆ9.4, 7.5Hz), 4.72 8ddd,
1H, Jˆ11.5, 9.5, 5.2 Hz), 4.26 8d, 1H, Jˆ7.6 Hz), 3.59 8dqd,
1H, Jˆ11.5, 6.2, 1.9 Hz), 3.45 8s, 3H), 2.97 8s, 3H), 2.22
8ddd, 1H, Jˆ12.9, 5.2, 1.9 Hz), 2.08 8s, 3H), 1.70 8dt, 1H,
Jˆ12.9, 11.5Hz), 1.28 8d, 3H, Jˆ6.2 Hz); 13C NMR d
169.95, 101.83, 77.72, 72.17, 67.64, 56.99, 39.57, 38.91,
21.21, 20.83.
1
8^)-50b: H NMR d 7.16±7.32 8m, 5H), 4.64 8d, 1H,
5.1.33. Epoxide ꢀ^)-6. Following the usual procedure, the
treatment of a solution of mesylate 8^)-35b 80.14 g,
0.49 mmol) in MeOH 81 mL) with MeONa 80.010 g)
Jˆ11.8 Hz), 4.56 8d, 1H, Jˆ11.8 Hz), 4.06 8d, 1H,
Jˆ7.3 Hz), 3.22±3.58 8m, 3H), 3.48 8s, 3H), 1.98 8ddd,

6084
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
afforded, after 24 h stirring at rt, a crude product which was
dissolved in anhydrous benzene 83 mL) and treated with
t-BuOK 80.102 g, 0.90 mmol). After 30 min stirring at rt,
evaporation of the ®ltered organic solution afforded pure
epoxide 8^)-6,21 as a liquid 80.049 g, 69% yield).
clear liquid, which turned out to be 57% ee, as determined
by chiral GC analysis on a CP-Cyclodex-B fused silica
capillary column 850 m£0.25mm) 8Chrompack): low
isotherm 808C, high isotherm 1208C, increasing temperature
48C/min.
5.1.34. Mesylates ꢀ^)-52b and 52a. A solution of the 9:1
mixture of alcohols 8^)-50b and 8^)-50a 80.204 g,
0.81 mmol) in anhydrous pyridine 85mL) was treated at
08C with MsCl 83.72 g, 3.25mmol). After 3 h, dilution
with CH2Cl2 and evaporation of the washed 8saturated
aqueous NaHCO3 and NaCl) organic solution afforded a
crude product consisting of a 9:1 mixture of mesylates
8^)-52b and 8^)-52a 80.25g, 93% yield).
5.2. Azidolysis of epoxides 3±8 with NaN3±NH4Cl
Generalprocedure . A solution of the epoxide 80.50 mmol)
in an 8:1 MeOH/H2O mixture 83.0 mL) was treated with
NaN3 80.160 g, 2.46 mmol) and NH4Cl 80.060 g, 1.12
mmol) and the resulting reaction mixture was stirred at
808C for the time shown in Tables 1 and 2. Evaporation
of the organic solvent afforded a crude product which was
®ltered through a silica gel pad 8a 7:3 hexane/AcOEt
mixture was used as the eluant) to give a crude reaction
8^)-52b: 1H NMR d 7.10±7.34 8m, 5H), 4.60 8d,
Jˆ11.8 Hz), 4.53 8d, Jˆ11.8 Hz), 4.27 8t, 1H, Jˆ8.3 Hz),
4.19 8d, 1H, Jˆ8.3 Hz), 3.56 8ddd, 1H, Jˆ11.5, 8.3, 5.3 Hz),
3.37±3.54 8m, 1H), 3.44 8s, 3H), 2.958s, 3H), 2.058ddd, 1H,
Jˆ13.0, 5.3, 1.8 Hz), 1.37 8dt, 1H, Jˆ13.0, 11.5Hz), 1.19
8d, 3H, Jˆ6.2 Hz); 13C NMR d 138.25, 128.95, 128.43,
128.35, 101.90, 83.55, 76.49, 72.15, 68.46, 57.24, 39.58,
38.94, 21.18.
1
mixture which was analyzed by H NMR 8Tables 1 and
2). In the case of epoxides 3 and 4, the reaction mixture
was diluted with ether, and the organic solution washed
8water) and evaporated.
The crude reaction mixture of azido alcohols from epoxide 8
80.084 g) was subjected to TLC 8a 95:5 CH2Cl2/AcOEt
mixture was used as the eluant). Extraction of the most
intense bands afforded the corresponding C-2 80.015g,
16% yield) and C-3 product 80.055 g, 59% yield).
1
8^)-52a: H NMR d 7.15±7.34 8m, 5H), 4.82 8d, 1H,
Jˆ3.6 Hz), 4.58 8d, Jˆ11.3 Hz), 4.44 8d, Jˆ11.3 Hz), 4.37
8dd, 1H, Jˆ9.8, 3.6 Hz), 3.90 8ddd, 1H, Jˆ11.1, 9.8,
5.2 Hz), 3.72±3.90 8m, 1H), 3.34 8s, 3H), 2.90 8s, 3H),
2.13 8ddd, 1H, Jˆ12.8, 5.2, 2.2 Hz), 1.35 8dt, 1H, Jˆ12.8,
11.5Hz), 1.14 8d, 3H, Jˆ6.2 Hz).
,1)-Methyl2-,azido)-2,4,6-trideoxy- a-d-altropyranoside
8C-2 product), a liquid 8Found: C, 44.74; H, 6.69; N,
22.30. C7H13N3O3 requires C, 44.91; H, 7.00; N, 22.45):
25
1
[a]D ˆ140.58 c 0.6, CHCl3); H NMR d 4.72±4.80 8br
s, 1H), 4.02±4.20 8m, 1H), 3.86±4.02 8m, 1H), 3.45±3.55
8m, 1H), 3.44 8s, 3H), 1.65±1.88 8m, 2H), 1.25 8d, 3H,
Jˆ6.3 Hz); 13C NMR d 100.35, 67.36, 60.60, 59.60,
56.27, 36.08, 21.54.
5.1.35. Hydroxy mesylate ꢀ^)-44b. A solution of the 9:1
mixture of mesylates 8^)-52b and 8^)-52a 80.165g,
0.50 mmol) in MeOH 82 mL) was hydrogenated at rt in
the presence of Pd/C 80.014 g). After 24 h, the usual
work-up afforded a crude solid product 80.115g) consisting
of the hydroxy mesylate 8^)-44b 81H and 13C NMR), which
was recrystallized from hexane/AcOEt to give pure 8^)-
44b, as a solid, mp 75.5±77.58C 80.098 g, 82% yield).
,1)-Methyl3-, b-azido)-3,4,6-trideoxy-a-d-glucopyrano-
side 8C-3 product), a liquid 8Found: C, 44.88; H, 6.93; N,
22.12. C7H13N3O3 requires C, 44.91; H, 7.00; N, 22.45):
25
1
[a]D ˆ1199.6 8c 1.2, CHCl3); H NMR d 4.74 8d, 1H,
Jˆ3.7 Hz), 3.90 8dqd, 1H, Jˆ11.7, 6.3, 2.1 Hz), 3.67
8ddd, 1H, Jˆ11.7, 9.9, 4.6 Hz), 3.50 8dd, 1H Jˆ9.9,
3.7 Hz), 3.36 8s, 3H), 1.958ddd, 1H, Jˆ13.1, 4.6, 2.1 Hz),
1.34 8dt, 1H, Jˆ13.1, 11.7 Hz), 1.21 8d, 3H, Jˆ6.3 Hz); 13C
NMR d 99.29, 72.61, 63.60, 60.04, 55.17, 37.52, 20.57.
5.1.36. Epoxide ꢀ^)-5. Following the usual procedure, the
treatment of a solution of hydroxy mesylate 8^)-44b
80.11 g, 0.46 mmol) in anhydrous benzene 83 mL) with
t-BuOK 80.102 g, 0.90 mmol) afforded pure epoxide 8^)-5
81H and 13C NMR),21 as a liquid 80.045g, 68% yield).
5.1.37. Diels±Alder reaction between Danishefsky diene
and acetaldehyde. Following a previously described pro-
cedure,25b a 25mL oven-dried schlenk was charged
with 8R,R)-8salen)Cr8III)±OTf complex 80.030 g, 0.042
The crude reaction product 80.092 g) from epoxide 7 was
subjected to ¯ash cromatography. Elution with an 85:15
hexane/AcOEt mixture afforded pure ,1)-methyl
3-,azido)-3,4,6-trideoxy-a-d-altropyranoside 8C-3 product)
80.082 g, 88% yield), as a liquid 8Found: C, 45.20; H, 7.19;
N, 22.54. C7H13N3O3 requires C, 44.91; H, 7.00; N, 22.45):
[a]D ˆ181.3 8c 3.0, CHCl3); H NMR d 4.56 8d, 1H,
Jˆ3.4 Hz), 4.158dqd, 1H, Jˆ8.2, 6.4, 3.8 Hz), 3.77 8q,
1H, Jˆ5.2 Hz), 3.57 8dd, 1H, Jˆ5.1, 3.4 Hz), 3.44 8s, 3H),
1.86 8ddd, 1H, Jˆ14.1, 8.2, 5.1 Hz), 1.67 8ddd, 1H, Jˆ14.1,
5.1, 3.8 Hz), 1.25 8d, 3H, Jˆ6.4 Hz); 13C NMR d 101.51,
69.80, 62.93, 58.60, 56.52, 33.27, 20.77.
mmol)25a and oven-dried powdered 4 A molecular sieves
Ê
80.60 g). The schlenk was sealed with a rubber septum
and purged with argon. The catalyst was dissolved in
TBME 80.5mL), and acetaldehyde 80.11 mL, 2.06 mmol)
was added via syringe at rt. The reaction mixture was then
cooled to 2308C followed by addition of diene 45
8Danishefsky diene) 80.4 mL, 2.05mmol). After 24 h
stirring at the same temperature, the reaction mixture was
diluted with CH2Cl2 85mL) and treated with two drops of
TFA. After 15min stirring at rt, the reaction mixture was
concentrated in vacuo and the crude residue was subjected
to ¯ash chromatography. Elution with a 7:3 hexane/AcOEt
mixture afforded pure enone 46 80.19 g, 82% yield), as a
25
1
The azido alcohols present in the crude reaction
mixture 80.086 g) from epoxide 6 turned out to be not
separable by TLC. Recrystallization of the crude
product from hexane/AcOEt afforded pure ,1)-methyl

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6085
3-,azido)-3,4,6-trideoxy-b-d-glucopyranoside 8C-3 product)
80.020 g, 21% yield), as a solid, mp 138.5±139.58C 8Found:
C, 45.08; H, 7.26; N, 22.68. C7H13N3O3 requires C, 44.91;
,1)-Benzyl3-,azido)-2,3,6-trideoxy- a-d-gulopyranoside 8C-3
product), a liquid 8Found: C, 59.55; H, 6.72; N, 15.88.
C13H17N3O3 requires C, 59.30; H, 6.51; N, 15.96):
H, 7.00; N, 22.45): [a]D ˆ127.58 c 0.5, CHCl3); 1H NMR
[a]D ˆ1220.4 8c 1.3, CHCl3); H NMR d 7.20±7.40 8m,
5H), 4.89 8unresolved dd, 1H, Jˆ4.1 Hz), 4.758d, 1H,
Jˆ12.4 Hz), 4.52 8d, 1H, Jˆ12.4 Hz), 4.28 8dq, 1H,
Jˆ6.7, 1.1 Hz), 3.83 8dd, 1H, Jˆ7.2, 3.8 Hz), 3.30±3.41
8m, 1H), 2.16 8dt, 1H, Jˆ15.2, 4.4 Hz), 1.82±1.92 8m,
1H), 1.17 8d, 3H, Jˆ6.7 Hz); 13C NMR d 138.46, 129.02,
128.20, 128.12, 95.72, 69.81, 62.71, 57.97, 27.61, 16.90
81£CH signals unresolved). Acetate, a solid, mp 41±
25
25
1
d 4.11 8d, 1H, Jˆ7.5Hz), 3.60 8dqd, 1H, Jˆ11.7, 6.2,
2.0 Hz), 3.52 8s, 3H), 3.48 8ddd, 1H, Jˆ11.7, 9.6, 5.0 Hz),
3.29 8dd, Jˆ9.6, 7.5Hz), 1.94 8ddd, 1H, Jˆ13.2, 5.0,
2.0 Hz), 1.38 8dt, 1H, Jˆ13.2, 11.7 Hz), 1.26 8d, 3H,
Jˆ6.2 Hz); 13C NMR d 104.64, 75.04, 69.29, 62.07,
57.75, 38.37, 21.42.
25
C-2 product. 1H NMR d 4.83 8d, 1H, Jˆ1.7 Hz), 3.99 8dqd,
1H, Jˆ10.0, 6.4, 3.1 Hz), 3.55 8s, 3H), 3.44±3.50 8m, 1H),
1.72 8ddd, 1H, Jˆ14.3, 10.0, 3.1 Hz), 1.38 8dt, 1H, Jˆ14.2,
3.1 Hz), 1.28 8d, 3H, Jˆ6.4 Hz).
42.58C 8recrystallized from hexane): [a]D ˆ1183.58 c
1
1.3, CHCl3); H NMR d 7.20±7.41 8m, 5H), 4.80 8dd, 1H,
Jˆ4.1, 1.4 Hz), 4.758d, 1H, Jˆ12.4 Hz), 4.53 8d, 1H,
Jˆ12.4 Hz), 4.61 8dd, 1H, Jˆ3.8, 1.5Hz), 4.30 8dq, 1H,
Jˆ6.7, 1.6 Hz), 3.87 8q, 1H, Jˆ3.8 Hz), 2.13 8s, 3H),
2.08±2.22 8m, 1H), 1.89±2.02 8m, 1H), 1.10 8d, 3H,
Jˆ6.7 Hz); 13C NMR d 170.89, 138.40, 128.99, 128.15,
95.49, 70.74, 69.86, 61.75, 55.24, 28.24, 21.48, 16.85
81£Ph signal unresolved).
The crude reaction product 80.091 g) from epoxide 5 was
subjected to ¯ash chromatography. Elution with a 98:2
CH2Cl2/MeOH mixture afforded pure ,1)-methyl
3-,azido)-3,4,6-trideoxy-b-d-altropyranoside 8C-3 product)
80.072 g, 77% yield), as a liquid 8Found: C, 44.58; H, 6.65;
N, 22.10. C7H13N3O3 requires C, 44.91; H, 7.00; N, 22.45):
,1)-Benzyl4-,azido)-2,4,6-trideoxy- a-d-glucopyranoside
8C-4 product), a solid, mp 71.5±72.58C 8recrystallized
from hexane) 8Found: C, 59.14; H, 6.41; N, 15.67.
C13H17N3O3 requires C, 59.30; H, 6.51; N, 15.96):
25
1
[a]D ˆ2134.4 8c 1.5, CHCl3); H NMR d 4.49 8d, 1H,
Jˆ1.5Hz), 3.90 8q, 1H, Jˆ3.0 Hz), 3.80 8dqd, 1H,
Jˆ10.0, 6.3, 3.0 Hz), 3.51±3.56 8m, 1H), 3.46 8s, 3H),
1.55 8dt, 1H, Jˆ14.0, 3.0 Hz), 1.67 8ddd, 1H, Jˆ14.0, 5.7,
3.0 Hz), 1.21 8d, 3H, Jˆ6.3 Hz); 13C NMR d 99.59, 68.26,
67.68, 59.84, 56.91, 32.53, 21.57.
25
1
[a]D ˆ1110.9 8c 0.8, CHCl3); H NMR d 7.20±7.40 8m,
5H), 4.97 8dd, 1H, Jˆ3.6, 1.0 Hz), 4.658d, 1H, Jˆ11.9 Hz),
4.44 8d, 1H, Jˆ11.9 Hz), 4.01 8ddd, 1H, Jˆ11.6, 9.6,
5.1 Hz), 3.67 8dq, 1H, Jˆ9.6, 6.2 Hz), 2.96 8t, 1H,
Jˆ9.7 Hz), 2.19 8ddd, 1H, Jˆ13.1, 5.1, 1.0 Hz), 1.73
8ddd, 1H, Jˆ13.1, 11.6, 3.6 Hz), 1.33 8d, 3H, Jˆ6.2 Hz);
13C NMR d 138.18, 129.17, 128.51, 97.17, 71.44, 69.71,
68.61, 67.40, 38.47, 19.23 81£Ph signal unresolved).
The crude reaction product 80.13 g) from epoxide 4 was
subjected to preparative TLC 8a 7:3 hexane/AcOEt mixture
was used as the eluant). Extraction of the two most intense
bands afforded the corresponding C-3 80.079 g, 60% yield)
and C-4 product 80.012 g, 9% yield).
5.2.1. Azidolysis of epoxides 3±8 with NaN3±LiClO4.
Generalprocedure . A solution of the epoxide 80.50 mmol)
in anhydrous CH3CN 81.0 mL) was treated with NaN3
80.045g, 0.70 mmol) and anhydrous LiClO 4 80.266 g,
2.5mmol) and the reaction mixture was stirred at 80 8C for
the time shown in Tables 1 and 2. Evaporation of the
organic solvent afforded a crude product which was ®ltered
through a silica gel pad 8a 7:3 hexane/AcOEt mixture was
used as the eluant) to give a crude reaction mixture which
,1)-Benzyl3-,azido)-2,3,6-trideoxy- a-d-glucopyranoside
8C-3 product), a liquid 8Found: C, 59.65; H, 6.34; N,
15.69. C13H17N3O3 requires C, 59.30; H, 6.51; N, 15.96):
25
1
[a]D ˆ1110.4 8c 1.9, CHCl3); H NMR d 7.20±7.40 8m,
5H), 4.95 8unresolved dd, 1H, Jˆ3.0 Hz), 4.68 8d, 1H,
Jˆ11.8 Hz), 4.46 8d, 1H, Jˆ11.8 Hz), 3.65±3.90 8m, 2H),
3.158t, 1H, Jˆ9.4 Hz), 2.20 8ddd, 1H, Jˆ13.1, 4.9, 1.0 Hz),
1.73 8td, 1H, Jˆ12.6, 3.5Hz), 1.30 8d, 3H, Jˆ6.2 Hz); 13C
NMR d 138.02, 129.13, 128.58, 96.28, 76.70, 69.60, 68.49,
61.05, 35.57, 18.39 81£Ph signal unresolved).
1
was analyzed by H NMR 8Tables 1 and 2). In the case of
epoxides 3 and 4, the reaction mixture was diluted
with ether, and the organic solution washed 8water) and
evaporated.
,1)-Benzyl4-,azido)-2,4,6-trideoxy- a-d-gulopyranoside 8C-4
product), a liquid 8Found: C, 59.26; H, 6.44; N, 15.73.
C13H17N3O3 requires C, 59.30; H, 6.51; N, 15.96):
5.2.2. Methanolysis of epoxides 3±8 with MeONa in
anhydrous MeOH. Generalprocedure . A solution of
the epoxide 80.50 mmol) in a freshly prepared 2 M
MeONa in anhydrous MeOH 82 mL) was stirred at 808C
for the time shown in Tables 1 and 2. Evaporation of the
neutralized 810% aqueous HCl) organic solution afforded a
25
1
[a]D ˆ1123.4 8c 1.1, CHCl3); H NMR d 7.20±7.40 8m,
5H), 5.01 8unresolved dd, 1H, Jˆ3.5Hz), 4.70 8d, 1H,
Jˆ11.8 Hz), 4.50 8d, 1H, Jˆ11.8 Hz), 4.33 8dq, 1H,
Jˆ6.5, 1.7 Hz), 3.97±4.10 8m, 1H), 3.31±3.40 8m, 1H),
2.11 8dt, 1H, Jˆ14.8, 3.5Hz), 1.88 8ddd, 1H, Jˆ14.7, 2.7,
1.2 Hz), 1.30 8d, 3H, Jˆ6.5Hz); 13C NMR d 137.47,
129.24, 128.76, 128.64, 97.75, 70.40, 67.15, 64.45, 61.57,
30.95, 18.04.
1
crude product which was analyzed by H NMR 8Tables 1
and 2).
The crude reaction mixture 80.084 g) of methoxy alcohols
from epoxide 8 was subjected to preparative TLC 8a 7:3
hexane/AcOEt mixture was used as the eluant). Extraction
of the two most intense bands afforded the corresponding
pure C-2 80.015g, 17% yield) and C-3 product 80.045g,
51% yield).
The crude reaction product 80.127 g) from epoxide 3 was
subjected to preparative TLC 8a 7:3 hexane/AcOEt mixture
was used as the eluant). Extraction of the two most intense
bands afforded the corresponding C-3 80.095g, 72% yield)
and C-4 product 80.007 g, 5% yield).

6086
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
,1)-Methyl2-,O-methy)l-4,6-dideoxy- a-d-altropyranoside
8C-2 product), a liquid 8Found: C, 54.36; H, 9.28. C8H16O4
8q, 1H Jˆ3.5Hz), 3.46 8s, 3H), 3.32 8s, 3H), 1.59 8dd, 1H,
Jˆ7.3, 2.9 Hz), 1.59 8dd, 1H, Jˆ6.0, 2.9 Hz), 1.17 8d, 3H,
Jˆ6.3 Hz); 13C NMR d 100.15, 78.16, 67.53, 67.45, 57.66,
56.99, 32.71, 21.81.
25
requires C, 54.53; H, 9.15): [a]D ˆ181.8 8c 1.1, CHCl3)
25
[lit.11 [a]D ˆ185.5 8c 1.82, CHCl3); lit.11b [a]D ˆ182.4
18
21
8c 1.5, CHCl3)]. Acetate, a liquid: [a]D ˆ184.58 c 0.9,
1
CHCl3); H NMR d 4.99 8q, 1H, Jˆ3.2 Hz), 4.658br s,
The crude reaction mixture 80.11 g) from epoxide 3 was
subjected to preparative TLC 8a 7:3 hexane /AcOEt was
used as the eluant). Extraction of the two most intense
bands afforded the corresponding C-3 80.075g, 60%
yield) and C-4 product 80.017 g, 13% yield).
1H), 4.00 8dqd, 1H, Jˆ10.7, 6.4, 3.2 Hz), 3.47 8s, 3H),
3.38 8s, 3H), 3.15±3.21 8m, 1H), 2.08 8s, 3H), 1.83 8ddd,
1H, Jˆ14.3, 10.7, 3.2 Hz), 1.60 8ddd, 1H, Jˆ14.3, 3.2,
2.6 Hz), 1.20 8d, 3H, Jˆ6.4 Hz); 13C NMR d 171.18,
100.25, 75.24, 67.88, 60.49, 59.02, 55.72, 33.23, 21.85,
21.47.
,1)-Benzyl2,6-dideoxy-3-,O-methy)l- a-d-gulopyranoside
8C-3 product), a liquid 8Found: C, 66.39; H, 7.68.
25
,1)-Methyl3-,O-methyl)-4,6-dideoxy- a-d-glucopyranoside
8C-3 product), a liquid 8Found: C, 54.17; H, 9.03. C8H16O4
C14H20O4 requires C, 66.65; H, 7.99): [a]D ˆ1139.7 8c
1
1.3, CHCl3); H NMR d 7.20±7.40 8m, 5H), 4.83 8dd, 1H,
25
requires C, 54.53; H, 9.15): [a]D ˆ1188.6 8c 1.6, CHCl3)
25
Jˆ4.2, 2.1 Hz), 4.758d, 1H, Jˆ12.5Hz), 4.52 8d, 1H,
Jˆ12.5Hz), 4.33 8q, 1H, Jˆ6.7 Hz), 3.37±3.60 8m, 2H),
3.42 8s, 3H), 1.84±2.10 8m, 2H), 1.18 8d, 3H, Jˆ6.7 Hz);
13C NMR d 138.78, 128.96, 128.33, 128.09, 96.10, 77.11,
69.63, 69.53, 63.26, 57.55, 28.59, 16.83. Acetate, a liquid:
[lit.11a [a]D ˆ1192.6 8c 1.27, CHCl3); lit.11b [a]D ˆ1192
18
23
8c 1.2, CHCl3)]. Acetate, a liquid: [a]D ˆ1166.2 8c 2.0,
1
CHCl3); H NMR d 4.858d, 1H, Jˆ3.7 Hz), 4.758dd, 1H,
Jˆ9.8, 3.7 Hz), 3.91 8dqd, 1H, Jˆ11.6, 6.3, 2.2 Hz), 3.67
8ddd, 1H, Jˆ11.6, 9.8, 5.0 Hz), 3.44 8s, 3H), 3.38 8s, 3H),
3.37 8s, 3H), 2.158ddd, 1H, Jˆ12.7, 5.0, 2.2 Hz), 1.34 8dt,
1H, Jˆ12.7, 11.6 Hz), 1.22 8d, 3H, Jˆ6.3 Hz); 13C NMR d
171.26, 98.29, 75.04, 74.98, 64.10, 57.90, 55.66, 38.69,
21.85, 21.54.
[a]D ˆ1128.4 8c 1.3, CHCl3); 1H NMR d 7.20±7.40
25
8m, 5H), 4.89 8t, 1H, Jˆ3.3 Hz), 4.82 8dd, 1H, Jˆ3.3,
1.3 Hz), 4.74 8d, 1H, Jˆ12.5Hz), 4.54 8d, 1H, Jˆ
12.5Hz), 4.35 8dq, 1H, Jˆ6.7, 1.3 Hz), 3.40±3.51 8m,
1H), 3.458s, 3H), 2.12 8s, 3H), 1.958t, 2H, Jˆ3.3 Hz),
1.10 8d, 3H, Jˆ6.7 Hz); 13C NMR d 171.21, 138.71,
128.93, 128.49, 128.09, 95.78, 74.35, 70.38, 69.53, 61.76,
57.86, 29.38, 21.63, 17.02.
The crude reaction product 80.087 g) from epoxide 7 was
subjected to ¯ash cromatography. Elution with an 1:1
hexane/AcOEt mixture afforded pure methyl3-,O-methy)l-
4,6-dideoxy-a-d-altropyranoside 8C-3 product) 80.078 g,
88% yield), as a liquid 8Found: C, 54.78; H, 9.41.
,1)-Benzyl2,6-dideoxy-4-O-methy-l a-d-glucopyranoside
8C-4 product), a solid, mp 120.5±122.58C 8recrystallized
from hexane) 8Found: C, 66.57; H, 8.11. C14H20O4 requires
25
C8H16O4 requires C, 54.53; H, 9.15): [a]D ˆ182.4 8c
1.2, CHCl3) [lit.11b [a]D ˆ183.4 8c 1.8, CHCl3)]. Acetate,
C, 66.65; H, 7.99): [a]D ˆ1132.2 8c 0.2, CHCl3); 1H NMR
23
25
25
1
a liquid: [a]D ˆ175.4 8c 1.1, CHCl3); H NMR d 4.81±
4.88 8m, 1H), 4.60 8broad s, 1H), 4.07±4.13 8dqd, 1H,
Jˆ9.7, 6.4, 3.5Hz), 3.35±3.57 8m, 1H), 3.44 8s, 3H), 3.40
8s, 3H), 2.10 8s, 3H), 1.58±1.82 8m, 2H), 1.21 8d, 3H,
Jˆ6.4 Hz); 13C NMR d 170.55, 100.18, 75.40, 67.00,
60.27, 58.05, 56.31, 33.59, 21.81 81£Me signals
unresolved).
d 7.20±7.41 8m, 5H), 4.93 8unresolved dd, 1H, Jˆ3.4 Hz),
4.66 8d, 1H, Jˆ11.9 Hz), 4.43 8d, 1H, Jˆ11.9 Hz), 4.02
8ddd, 1H, Jˆ11.6, 9.2, 5.4 Hz), 3.69 8dq, 1H, Jˆ9.2,
6.3 Hz), 3.58 8s, 3H), 2.74 8t, 1H, Jˆ9.2 Hz), 2.18 8ddd,
1H, Jˆ12.8, 5.4, 1.0 Hz), 1.71 8ddd, 1H, Jˆ12.8, 11.6,
3.7 Hz), 1.30 8d, 3H, Jˆ6.3 Hz); 13C NMR d 138.46,
129.08, 128.46, 128.34, 97.16, 88.79, 69.49, 69.38, 67.89,
61.60, 38.20, 18.87.
The methoxy alcohols contained in the crude reaction
mixture 80.086 g) from epoxide 6 turned out to be not separ-
able by TLC. Acetylation afforded a crude reaction product
5.2.3. Methanolysis of epoxides 3±8 with MeOH±
LiClO4. Generalprocedure . A solution of the epoxide
80.50 mmol) in anhydrous MeOH 82.0 mL) containing
anhydrous LiClO4 83.60 g, 34.0 mmol) was stirred at 808C
for the time shown in Tables 1 and 2. After cooling, dilution
with water, extraction with ether, and evaporation of the
washed 8saturated aqueous NaCl) ether extracts afforded a
1
80.092 g, 84% yield) which was analyzed by H NMR.
1
C-2 product. H NMR d 5.09 8q, 1H, Jˆ3.2 Hz), 4.48 8d,
1H, Jˆ1.2 Hz), 3.77 8dqd, 1H, Jˆ11.1, 6.3, 2.6 Hz), 3.15
8dd, 1H, Jˆ3.2, 1.2 Hz), 2.03 8s, 3H), 1.72 8ddd, 1H,
Jˆ14.5, 11.1, 3.2 Hz), 1.52 8dt, 1H, Jˆ14.5, 2.6 Hz), 1.18
8d, 3H, Jˆ6.3 Hz).
1
crude product which was analyzed by H NMR 8Tables 1
and 2). In the case of epoxides 5±8, the crude product was
®ltered through a silica gel pad 8an 1:1 hexane/AcOEt
mixture was used as the eluant).
C-3 product. 1H NMR d 4.70 8dd, 1H, Jˆ9.3, 8.0 Hz), 4.17
8d, 1H, Jˆ8.0 Hz), 2.03 8s, 3H), 1.31 8dt, 1H, Jˆ12.8,
11.6 Hz), 1.22 8d, 3H, Jˆ6.3 Hz).
The crude product 80.11 g) from epoxide 4 was subjected to
preparative TLC 8an 1:1 hexane/AcOEt was used as the
eluant). Extraction of the two most intense bands afforded
the corresponding C-3 80.008 g, 6% yield) and C-4 product
80.084 g, 67% yield):
The crude reaction product 80.062 g, 70% yield) from
epoxide 5 turned out to be consisting of practically pure
,2)-methyl3-,O-methy)l-4,6-dideoxy- b-d-altropyranoside
8C-3 product), as a liquid 8Found: C, 54.82; H, 9.39.
25
C8H16O4 requires C, 54.53; H, 9.15): [a]D ˆ267.6 8c
,1)-Benzyl2,6-dideoxy-4-,O-methy)-l a-d-gulopyranoside
8C-4 product), a liquid 8Found: C, 66.92; H, 7.60.
1
0.9, CHCl3); H NMR d 4.51 8d, 1H, Jˆ1.3 Hz), 3.79
25
8sextet, 1H, Jˆ6.3 Hz), 3.61 8dd, 1H, Jˆ3.5, 1.3 Hz), 3.51
C14H20O4 requires C, 66.65; H, 7.99): [a]D ˆ196.58 c

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6087
1.2, CHCl3); 1H NMR d 7.20±7.40 8m, 5H), 5.01
8unresolved dd, 1H, Jˆ3.4 Hz), 4.72 8d, 1H, Jˆ11.9 Hz),
4.52 8d, 1H, Jˆ11.9 Hz), 4.258dq, 1H, Jˆ6.5, 1.3 Hz),
3.97±4.10 8m, 1H), 3.46 8s, 3H), 2.98±3.04 8m, 1H), 2.14
8dt, 1H, Jˆ14.6, 3.6 Hz), 1.84 8ddd, 1H, Jˆ14.6, 2.8,
1.2 Hz), 1.27 8d, 3H, Jˆ6.5Hz); 13C NMR d 137.85,
129.16, 128.55, 98.06, 80.45, 70.15, 65.00, 62.32, 59.65,
31.00, 17.10 81£Ph signal unresolved).
1.06 8t, 6H, Jˆ7.1 Hz); 13C NMR d 103.40, 70.45, 66.83,
58.03, 56.37, 44.01, 28.28, 20.67, 15.04.
The crude reaction mixture of amino alcohols 80.087 g, 80%
yield) from epoxide 8 was acetylated to give a correspond-
ing mixture 80.090 g, 69% yield) of acetylated C-2 and C-3
product 81H NMR, Table 2) which were subjected to
preparative TLC 8an 8:2 hexane/acetone mixture was used
as the eluant). Extraction of the faster moving band afforded
pure ,1)-methyl 2-,N,N-diethylamino)-3-,O-acetyl)-2,4,6-
trideoxy-a-d-altropyranoside 8C-2 product) 80.010 g, 8%
yield), as a liquid 8Found: C, 60.53; H, 10.07; N, 5.19.
C13H25NO4 requires C, 60.21; H, 9.72; N, 5.40):
,1)-Benzyl2,6-dideoxy-3-,O-methyl)- a-d-glucopyranoside
8C-3 product), a liquid 8Found: C, 66.47; H, 7.81. C14H20O4
25
requires C, 66.65; H, 7.99): [a]D ˆ1107.4 8c 1.2, CHCl3);
1H NMR d 7.20±7.40 8m, 5H), 4.99 8unresolved dd, 1H,
Jˆ3.1 Hz), 4.69 8d, 1H, Jˆ11.9 Hz), 4.458d, 1H,
Jˆ11.9 Hz), 3.76 8dq, 1H, Jˆ9.1, 6.3 Hz), 3.57 8ddd, 1H,
Jˆ11.4, 9.1, 4.9 Hz), 3.39 8s, 3H), 3.19 8td, 1H, Jˆ9.1,
1.7 Hz), 2.58 8d, 1H 8OH), Jˆ1.7 Hz), 2.32 8ddd, 1H,
Jˆ12.8, 4.9, 1.1 Hz), 1.53 8ddd, 1H, Jˆ12.8, 11.4,
3.7 Hz), 1.31 8d, 3H, Jˆ6.3 Hz); 13C NMR d 138.34,
129.05, 128.58, 128.37, 97.23, 78.95, 76.72, 69.42, 68.31,
25
1
[a]D ˆ176.4 8c 1.3, CHCl3); H NMR d 5.11 8q, 1H,
Jˆ6.0 Hz), 4.658d, 1H, Jˆ2.7 Hz), 4.10 8sextet, 1H,
Jˆ6.0 Hz), 3.37 8s, 3H), 2.76 8dd, 1H, Jˆ6.0, 2.7 Hz),
2.71 8dq, 2H, Jˆ13.0, 7.2 Hz), 2.58 8dq, 2H, Jˆ13.0,
7.2 Hz), 2.058s, 3H), 1.76 8t, 2H, Jˆ6.0 Hz), 1.24 8d, 3H,
Jˆ6.0 Hz), 1.02 8t, 6H, Jˆ7.2 Hz); 13C NMR d 171.07,
102.20, 67.64, 62.36, 62.13, 55.69, 45.17, 35.63, 22.11,
21.81, 14.95.
25
57.11, 34.55, 18.52. Acetate, a liquid: [a]D ˆ195.5 8c 1.2,
1
CHCl3); H NMR d 7.20±7.40 8m, 5H), 4.99 8unresolved
dd, 1H, Jˆ3.1 Hz), 4.70 8t, 1H, Jˆ9.2 Hz), 4.67 8d, 1H,
Jˆ12.0 Hz), 4.46 8d, 1H, Jˆ12.0 Hz), 3.82 8dq, 1H,
Jˆ9.2, 6.3 Hz), 3.68 8ddd, 1H, Jˆ11.3, 9.2, 5.0 Hz), 3.33
8s, 3H), 2.32 8ddd, 1H, Jˆ13.0, 5.0, 1.0 Hz), 2.10 8s, 3H),
1.66 8ddd, 1H, Jˆ13.0, 11.3, 3.7 Hz), 1.16 8d, 3H,
Jˆ6.3 Hz); 13C NMR d 170.93, 138.26, 129.10, 128.55,
128.44, 97.13, 76.86, 76.32, 69.61, 66.70, 57.61, 35.44,
21.76, 18.21.
Extraction of the slower moving band afforded an 85:15
mixture of the corresponding free and acetylated C-3
product 80.058 g) which was dissolved in MeOH and treated
with MeONa 80.010 g). After 24 h stirring at rt, evaporation
of the solvent afforded a crude product which was ®ltered
trough a short silica gel pad 8ether was used as eluant) to
give pure ,1)-methyl3-,N,N-diethyal mino)-3,4,6-trideoxy-
a-d-glucopyranoside 8C-3 product) 80.045g, 41% yield), as
a liquid 8Found: C, 61.08; H, 10.42; N, 6.11. C11H23NO3
25
5.2.4. Methanolysis of epoxide 4 with 0.2N H2SO4 in
solution of the epoxide
requires C, 60.80; H, 10.67; N, 6.45): [a]D ˆ1158.7 8c
1
anhydrous MeOH.
A
0.7, CHCl3); H NMR d 4.90 8d, 1H, Jˆ3.9 Hz), 3.91
80.50 mmol) in 0.2N H2SO4 in anhydrous MeOH 85mL)
was stirred at rt for 1 h. Dilution with saturated aqueous
NaHCO3, extraction with Et2O and evaporation of the
ether extracts afforded a crude liquid product which was
8dqd, 1H, Jˆ12.0, 6.0, 2.4 Hz), 3.52 8dd, 1H, Jˆ10.7,
3.9 Hz), 3.44 8s, 3H), 3.07 8ddd, 1H, Jˆ12.0, 10.7,
3.9 Hz), 2.64 8dq, 2H, Jˆ13.0, 7.3 Hz), 2.39 8dq, 2H,
Jˆ13.0, 7.3 Hz), 1.73 8ddd, 2H, Jˆ12.5, 3.9, 2.4 Hz), 1.30
8q, 1H, Jˆ12.0 Hz), 1.19 8d, 3H, Jˆ6.0 Hz), 1.058t, 6H,
Jˆ7.3 Hz); 13C NMR d 100.18, 68.88, 65.64, 57.96, 55.68,
43.84, 32.29, 21.98, 15.11.
1
analyzed by H NMR 8Table 2).
5.2.5. Aminolysis of epoxides 3±8 with NHEt2±EtOH.
Generalprocedure . A solution of the epoxide 80.50 mmol)
in anhydrous EtOH 84 mL) was treated with NHEt2
80.25mL, 2.5mmol) and the resulting reaction mixture
was stirred at 808C for the time shown in Tables 1 and 2.
Evaporation of the organic solvent afforded a crude product
which was ®ltered through a silica gel pad 8a 7:2:1 hexane/
AcOEt/NEt3 mixture was used as the eluant) to give a crude
The amino alcohols 81H NMR) contained in the crude reac-
tion mixture 80.086 g, 79% yield) from epoxide 6 turned out
to be not separable by preparative TLC. The crude mixture
was acetylated to give a mixture 80.084 g, 65% yield) of the
corresponding acetates, not separable, as well.
1
1
product which was analyzed by H NMR 8Tables 1 and 2).
C-2 product. H NMR d 4.76 8d, 1H, Jˆ3.0 Hz), 3.29 8s,
In the case of epoxides 3 and 4, the reaction mixture was
diluted with ether and the organic solution washed 8water)
and evaporated.
3H), 2.79 8dq, 2H, Jˆ14.2, 7.1 Hz), 2.03 8ddd, 1H, Jˆ12.9,
4.9, 2.7 Hz), 1.76 8ddd, 1H, Jˆ12.9, 9.5, 6.0 Hz), 1.30 8d,
3H, Jˆ6.3 Hz), 0.96 8t, 6H, Jˆ7.1 Hz). Acetate: 1H NMR d
5.27 8ddd, 1H, Jˆ7.1, 5.3, 2.1 Hz), 4.61 8d, 1H, Jˆ2.9 Hz),
4.05±3.88 8m, 1H), 3.34 8s, 3H), 2.85 8dd, 1H, Jˆ7.3,
2.9 Hz), 1.99 8s, 3H), 1.22 8d, 3H, Jˆ6.3 Hz), 0.93 8t, 6H,
Jˆ7.3 Hz).
The crude reaction product from epoxide 7 turned out to be
constituted of practically pure ,2)-methyl3-,N,N-diethy-l
amino)-3,4,6-trideoxy-a-d-altropyranoside 8C-3 product)
80.107 g, 99% yield), as a liquid 8Found: C, 60.54; H,
10.41; N, 6.76. C11H23NO3 requires C, 60.80; H, 10.67; N,
1
C-3 product. H NMR d 4.13 8d, 1H, Jˆ7.4 Hz), 3.50 8s,
25
1
6.45): [a]D ˆ235.0 8c 2.3, CHCl3); H NMR d 4.50 8d,
1H, Jˆ6.2 Hz), 4.21 8sextet, 1H, Jˆ6.3 Hz), 3.48 8s, 3H),
3.39 8dd, 1H, Jˆ11.0, 6.2 Hz), 2.88 8td, 1H, Jˆ11.0,
6.2 Hz), 2.64 8dq, 2H, Jˆ14.2, 7.1 Hz), 2.39 8dq, 2H,
Jˆ14.2, 7.1 Hz), 1.74 8ddd, 1H, Jˆ12.9, 11.0, 6.2 Hz),
1.56 8dt, 1H, Jˆ12.9, 6.2 Hz), 1.26 8d, 3H, Jˆ6.3 Hz),
3H), 3.13 8dd, 1H, Jˆ10.1, 7.4 Hz), 2.29 8dq, 2H, Jˆ13.3,
7.1 Hz), 1.63 8ddd, 1H, Jˆ12.8, 3.9, 2.1 Hz), 1.20 8d, 3H,
Jˆ6.1 Hz), 0.98 8t, 6H, Jˆ7.1 Hz). Acetate: 1H NMR d 4.70
8dd, 1H, Jˆ10.5, 7.6 Hz), 4.18 8d, 1H, Jˆ7.6 Hz), 3.41 8s,
3H), 2.26 8dq, 2H, Jˆ13.3, 7.0 Hz), 1.99 8s, 3H), 1.20 8d,
3H, Jˆ6.0 Hz), 0.89 8t, 6H, Jˆ7.0 Hz).

6088
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
The crude reaction product 80.091 g) from epoxide 5 was
subjected to ¯ash cromatography. Elution with a 5:5:0.2
CH2Cl2/hexane/NEt3 mixture afforded pure ,2)-methyl3-
,N,N-diethylamino)-3,4,6-trideoxy-b-d-altropyranoside
8C-3 product) 80.072 g, 66% yield), as a liquid 8Found: C,
60.49; H, 10.53; N, 6.75. C11H23NO3 requires C, 60.80; H,
7.0 Hz), 2.49±2.758m, 3H), 2.13 8dt, 1H, Jˆ14.2, 3.6 Hz),
1.91 8dt, 1H, Jˆ14.2, 3.6 Hz), 1.26 8d, 3H, Jˆ6.7 Hz), 1.03
8t, 6H, Jˆ7.0 Hz); 13C NMR d 138.08, 129.13, 128.58,
128.49, 97.16, 70.00, 65.05, 64.12, 62.89, 45.68, 35.49,
18.01, 15.69.
10.67; N, 6.45): [a]D ˆ2147.2 8c 1.3, CHCl3); 1H NMR d
,1)-Benzyl3-,N,N-diethylamino)-2,3,6-trideoxy- a-d-gluco-
pyranoside 8C-3 product), a semisolid 8Found: C, 69.19; H,
9.02; N, 4.39. C17H27NO3 requires C, 69.59; H, 9.28; N,
25
4.80 8d, 1H, Jˆ3.3 Hz), 4.09 8dqd, 1H, Jˆ6.9, 5.4, 4.0 Hz),
3.53 8dd, 1H, Jˆ9.5, 3.3 Hz), 3.42 8s, 3H), 3.13 8td, 1H,
Jˆ9.5, 4.0 Hz), 2.60 8dq, 2H, Jˆ13.8, 6.8 Hz), 2.38 8dq,
2H, Jˆ13.5, 6.8 Hz), 1.75 8ddd, 1H, Jˆ13.3, 9.5, 5.4 Hz),
1.58 8dt, 1H, Jˆ13.3, 4.0 Hz), 1.30 8d, 3H, Jˆ6.9 Hz), 0.98
8t, 6H, Jˆ6.8 Hz); 13C NMR d 101.36, 70.08, 68.84, 56.45,
25
1
4.77): [a]D ˆ142.9 8c 0.7, CHCl3); H NMR d 7.20±
7.40 8m, 5H), 4.99 8unresolved dd, 1H, Jˆ2.8 Hz), 4.71 8d,
1H, Jˆ12.1 Hz), 4.46 8d, 1H, Jˆ12.1 Hz), 3.99 8dq, 2H,
Jˆ14.2, 7.1 Hz), 3.76 8dq, 1H, Jˆ8.4, 6.2 Hz), 2.98±3.17
8m, 2H), 2.34 8dq, 2H, Jˆ14.2, 7.1 Hz), 1.80±1.96 8m,
1H), 1.55±1.74 8m, 1H), 1.31 8d, 3H, Jˆ6.2 Hz), 1.058t,
6H, Jˆ7.1 Hz); 13C NMR d 138.66, 129.01, 128.40,
128.21, 97.47, 72.09, 70.01, 69.22, 58.84, 43.75, 28.75,
19.10, 15.27.
1
54.37, 43.55, 29.68, 22.44, 14.35. Acetate, a liquid: H
NMR d 4.96 8dd, 1H, Jˆ5.1, 1.9 Hz), 4.74 8d, 1H,
Jˆ1.9 Hz), 3.92 8dqd, 1H, Jˆ8.5, 6.4, 3.5 Hz), 3.41 8s,
3H), 2.89 8q, 1H, Jˆ5.0 Hz), 2.61 8dq, 2H, Jˆ14.0,
7.0 Hz), 2.53 8dq, 2H, Jˆ13.9, 7.0 Hz), 2.058s, 3H), 1.70
8ddd, 1H, Jˆ14.5, 5.0, 3.5 Hz), 1.56 8ddd, 1H, Jˆ14.5, 8.5,
5.0 Hz), 1.22 8d, 3H, Jˆ6.4 Hz), 0.91 8t, 6H, Jˆ7.0 Hz); 13C
NMR d 171.09, 99.21, 69.12, 68.37, 56.85, 55.87, 43.36,
31.76, 21.97, 21.73, 12.49.
5.2.7. Reaction of epoxides 3±8 with PhSH±NEt3.
Generalprocedure . A solution of the epoxide 80.50 mmol)
in MeOH 80.5mL) was treated with PhSH 80.153 mL,
1.50 mmol) and NEt3 80.26 mL, 2.0 mmol) and the resulting
reaction mixture was stirred at rt for the time shown in
Tables 1 and 2. Evaporation of the solvent afforded a
The crude reaction product 80.142 g) from epoxide 3 was
subjected to preparative TLC 8an 85:15:5 hexane/AcOEt/
NEt3 mixture was used as the eluant). Extraction of the
most intense band afforded pure ,1)-benzyl3-,N,N-diethyl-
amino)-2,3,6-trideoxy-a-d-gulopyranoside 8C-3 product)
80.110 g, 75% yield), as a liquid 8Found: C, 69.75; H,
9.42; N, 4.86. C17H27NO3 requires C, 69.59; H, 9.28; N,
1
crude product which was analyzed by H NMR 8Tables 1
and 2).
The crude reaction mixture 80.165g) from epoxide 3 was
subjected to preparative TLC 8a 7:3 hexane/AcOEt mixture
was used as the eluant). Extraction of the two most intense
bands afforded the corresponding C-3 80.128 g, 78% yield)
and C-4 product 80.008 g, 5% yield).
25
1
4.77): [a]D ˆ1152.2 8c 2.7, CHCl3); H NMR d 7.20±
7.40 8m, 5H), 4.83 8dd, 1H, Jˆ8.9, 3.6 Hz), 4.82 8d, 1H,
Jˆ11.8 Hz), 4.53 8d, 1H, Jˆ11.8 Hz), 4.41 8dq, 1H, Jˆ6.9,
5.6 Hz), 3.68 8dd, 1H, Jˆ9.7, 5.6 Hz), 2.55±2.85 8m, 3H),
2.37 8dq, 2H, Jˆ14.2, 7.1 Hz), 1.97 8dt, 1H, Jˆ12.7,
3.6 Hz), 1.53 8dt, 1H, Jˆ12.7, 8.9 Hz), 1.258d, 3H,
Jˆ6.9 Hz), 1.04 8t, 6H, Jˆ7.1 Hz); 13C NMR d 138.34,
129.05, 128.70, 128.36, 96.13, 70.83, 70.47, 68.58, 58.11,
44.02, 29.74, 15.07, 13.46.
,1)-Benzyl4-,thiophen)-y2l,4,6-trideoxy- a-d-glucopyra-
noside 8C-4 product), a solid, mp 72±738C 8recrystallized
from hexane) 8Found: C, 69.21; H, 6.44. C19H22O3S
25
requires C, 69.06; H, 6.71): [a]D ˆ170.8 8c 0.5, CHCl3);
1H NMR d 7.41±7.55 8m, 2H), 7.15±7.40 8m, 8H), 5.00
8dd, 1H, Jˆ3.5, 1.3 Hz), 4.62 8d, 1H, Jˆ12.0 Hz), 4.40 8d,
1H, Jˆ12.0 Hz), 3.958dt, 1H, Jˆ10.8, 5.0 Hz), 3.80 8dq,
1H, Jˆ10.6, 6.2 Hz), 2.63 8t, 1H, Jˆ10.5Hz), 2.29 8ddd,
1H, Jˆ13.0, 4.9, 1.3 Hz), 1.76 8ddd, 1H, Jˆ12.9, 11.3,
3.5Hz), 1.37 8d, 3H, Jˆ6.2 Hz); 13C NMR d 138.42,
133.92, 133.40, 129.83, 129.06, 128.55, 128.27, 97.24,
69.47, 68.51, 66.15, 61.78, 38.53, 20.09 81£Ph signals
unresolved).
5.2.6. Aminolysis of epoxides 3±8 with NHEt2±LiClO4.
Generalprocedure . A solution of the epoxide 80.50 mmol)
in anhydrous CH3CN 84.0 mL) was treated with NHEt2
80.25mL, 2.5mmol) and anhydrous LiClO
81.06 g,
4
10.0 mmol) and the reaction mixture was stirred at 808C
for the time shown in Tables 1 and 2. Dilution with ether
and evaporation of the washed 8water) ether extracts
1
afforded a crude liquid product which was analyzed by H
NMR 8Tables 1 and 2).
,1)-Benzyl3-,thiopheny)l-2,3,6-trideoxy- a-d-gulopyrano-
side 8C-3 product), a liquid 8Found: C, 68.81; H, 6.35.
25
The crude product 80.145g) from epoxide 4 was subjected
to preparative TLC 8a 9:1 hexane/NEt3 mixture was used as
the eluant). Extraction of the two most intense bands
afforded the corresponding C-3 80.065g, 44% yield) and
C-4 product 80.053 g, 36% yield).
C19H22O3S requires C, 69.06; H, 6.71): [a]D ˆ152.0 8c
1
1.6, CHCl3); H NMR d 7.10±7.50 8m, 10H), 4.89 8dd,
1H, Jˆ3.7, 1.3 Hz), 4.79 8d, 1H, Jˆ12.4 Hz), 4.52 8d, 1H,
Jˆ12.4 Hz), 4.55 8q, 1H, Jˆ6.8 Hz), 3.40±3.55 8m, 2H),
2.458ddd, 1H, Jˆ14.9, 5.5, 4.2 Hz), 1.95 8ddd, 1H,
Jˆ14.9, 3.5, 1.7 Hz), 1.17 8d, 3H, Jˆ6.8 Hz); 13C NMR d
138.52, 136.90, 131.11, 129.69, 128.96, 128.11, 127.38,
96.24, 70.58, 69.64, 63.12, 45.88, 30.30, 17.19 81£Ph
signals unresolved).
,1)-Benzyl4-,N,N-diethyalmino)-2,4,6-trideoxy- a-d-gulo-
pyranoside 8C-4 product), a liquid 8Found: C, 69.32; H,
9.14; N, 4.53. C17H27NO3 requires C, 69.59; H, 9.28; N,
25
1
4.77): [a]D ˆ170.2 8c 0.8, CHCl3); H NMR d 7.18±
7.40 8m, 5H), 4.98 8t, 1H, Jˆ3.6 Hz), 4.73 8d, 1H,
Jˆ11.9 Hz), 4.50 8d, 1H, Jˆ11.9 Hz), 4.41 8dq, 1H,
Jˆ6.7, 4.5Hz), 3.90±4.02 8m, 1H), 2.81 8dq, 2H, Jˆ13.8,
The crude reaction mixture 80.125g) from epoxide 8 was
subjected to preparative TLC 8an 85:15 hexane/AcOEt
mixture was used as the eluant). Extraction of the most

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6089
intense bands afforded the corresponding C-2 80.035g, 28%
yield) and C-3 product 80.076 g, 60% yield).
131.72, 129.59, 127.46, 100.36, 72.65, 68.74, 57.28, 51.37,
33.42, 21.73, 21.85.
,1)-Methyl2-,thiophenyl)-2,4,6-trideoxy- a-d-altropyrano-
side 8C-2 product), a liquid 8Found: C, 61.28; H, 7.32.
,2)-Methyl 3-,thiophenyl)-2-,O-acetyl)-3,4,6-trideoxy-b-
d-glucopyranoside 8C-3 product), a liquid 8Found: C,
60.46; H, 6.69. C15H20O4S requires C, 60.79; H, 6.80):
25
C13H18O3S requires C, 61.39; H, 7.13): [a]D ˆ16.0 8c
1
1.9, CHCl3); H NMR d 7.10±7.41 8br s, 5H), 4.79 8m,
25
1
[a]D ˆ23.0 8c 2.1, CHCl3); H NMR d 7.31±7.51 8m,
2H), 7.11±7.31 8m, 3H), 4.73 8dd, Jˆ10.7, 7.7 Hz), 4.19
8d, 1H, Jˆ7.7 Hz), 3.54 8dqd, 1H, Jˆ11.0, 6.2, 1.9 Hz),
3.38 8s, 3H), 3.12 8ddd, 1H, Jˆ13.0, 10.7, 4.4 Hz), 1.93
8ddd, 1H, Jˆ13.0, 4.4, 1.9 Hz), 1.88 8s, 3H), 1.34 8td, 1H,
Jˆ13.0, 11.0 Hz), 1.14 8d, 3H, Jˆ6.2 Hz); 13C NMR d
170.57, 134.45, 133.16, 129.58, 128.50, 103.62, 73.77,
71.09, 57.05, 48.15, 40.11, 21.50, 21.30.
1H), 3.91±4.18 8m, 2H), 3.24±3.40 8m, 1H), 3.32 8s, 3H),
1.93 8ddd, 1H, Jˆ14.1, 11.6, 2.7 Hz), 1.56±1.71 8m, 1H),
1.19 8d, 3H, Jˆ6.3 Hz); 13C NMR d 135.18, 131.60, 129.87,
127.87, 102.23, 68.64, 60.36, 56.06, 50.05, 36.07, 21.81.
,1)-Methyl3-,thiophen)y-3l ,4,6-trideoxy- a-d-glucopyra-
noside 8C-3 product), a liquid 8Found: C, 61.23; H, 7.01.
25
C13H18O3S requires C, 61.39; H, 7.13): [a]D ˆ1171.58 c
0.8, CHCl3); 1H NMR d 7.42±7.58 8m, 2H), 7.20±7.42 8m,
3H), 4.758d, 1H, Jˆ3.3 Hz), 3.87 8dqd, 1H, Jˆ11.7, 6.2,
2.2 Hz), 3.33±3.56 8m, 1H), 3.43 8s, 3H), 3.31 8dt, Jˆ11.7,
3.9 Hz), 1.97 8ddd, 1H, Jˆ13.5, 3.9, 2.2 Hz), 1.38 8dt, 1H,
Jˆ13.5, 11.7 Hz), 1.12 8d, 3H, Jˆ6.2 Hz); 13C NMR d
134.97, 132.61, 129.61, 128.64, 100.02, 71.70, 65.38,
The crude reaction product 80.126 g) from epoxide 5 was
subjected to ¯ash cromatography. Elution with a 6:4
hexane/Et2O mixture afforded pure ,2)-methyl3-,thio-
phenyl)-3,4,6-trideoxy-b-d-altropyranoside 8C-3 product)
80.093 g, 73% yield), as a liquid 8Found: C, 61.43; H,
7.22. C13H18O3S requires C, 61.39; H, 7.13):
25
1
55.75, 48.30, 40.50, 21.31. Acetate,
a
liquid:
[a]D ˆ228.4 8c 2.1, CHCl3); H NMR d 7.10±7.41 8m,
5H), 4.73 8d, 1H, Jˆ0.7 Hz), 3.87 8dqd, 1H, Jˆ10.6, 6.3,
2.4 Hz), 3.53±3.66 8m, 2H), 3.45 8s, 3H), 1.99 8ddd, 1H,
Jˆ14.5, 10.6, 4.0 Hz), 1.58 8dt, 1H, Jˆ14.1, 2.4 Hz), 1.78
8d, 3H, Jˆ6.3 Hz); 13C NMR d 134.78, 131.66, 129.81,
127.73, 99.60, 68.56, 56.89, 46.93, 33.30, 21.78 81£CH
25
1
[a]D ˆ191.9 8c 1.8, CHCl3); H NMR d 7.47±7.52 8m,
2H), 7.17±7.47 8m, 3H), 4.83 8dd, 1H, Jˆ11.0, 3.5Hz), 4.76
8d, 1H, Jˆ3.5), 3.92 8dqd, 1H, Jˆ12.4, 6.2, 4.2 Hz), 3.61
8ddd, 1H, Jˆ12.4, 11.0, 4.2 Hz), 3.38 8s, 3H), 2.058ddd, 1H,
Jˆ13.5, 4.2, 2.2 Hz), 1.98 8s, 3H), 1.46 8dt, 1H, Jˆ13.2,
12.4 Hz), 1.158d, 3H, Jˆ6.2 Hz); 13C NMR d 171.15,
133.84, 129.56, 128.18, 97.92, 74.09, 64.94, 55.60, 44.04,
40.47, 21.50, 21.26 81£Ph signal unresolved).
25
signals unresolved). Acetate, a liquid: [a]D ˆ267.1 8c
1
1.5, CHCl3); H NMR d 7.38 8dd, 2H, Jˆ8.2, 1.4 Hz),
7.10±7.21 8m, 3H), 4.89 8dd, 1H, Jˆ3.2, 1.3 Hz), 4.858d,
1H, Jˆ1.3 Hz), 3.92 8dqd, 1H, Jˆ10.6, 6.2, 2.3 Hz), 3.55±
3.658m, 1H), 3.458s, 3H), 2.04 8s, 3H), 1.92 8ddd, 1H,
Jˆ14.2, 10.6, 4.7 Hz), 1.658dt, 1H, Jˆ14.2, 2.3 Hz), 1.22
8d, 3H, Jˆ6.2 Hz); 13C NMR d 171.00, 134.50, 131.33,
129.82, 127.80, 98.66, 69.76, 68.60, 57.34, 45.24, 34.12,
21.73 81£Me signals unresolved).
The crude reaction product 80.127 g) from epoxide 7 was
subjected to ¯ash cromatography. Elution with a 7:3
hexane/AcOEt mixture afforded pure ,2)-methyl3-,thio-
phenyl)-3,4,6-trideoxy-a-d-altropyranoside 8C-3 product)
80.119 g, 94% yield), as a liquid 8Found: C, 61.44; H,
25
7.21. C13H18O3S requires C, 61.39; H, 7.13): [a]D ˆ22.0
1
8c 2.9, CHCl3); H NMR d 7.36±7.48 8m, 2H), 7.17±7.36
5.2.8. Reaction of epoxides 3±8 with PhSH±LiClO4.
Generalprocedure . A solution of the epoxide 80.50 mmol)
in anhydrous MeCN 81.0 mL) containing PhSH 80.077 mL,
0.75mmol) and anhydrous LiClO 4 80.266 g, 2.5mmol) was
stirred at 808C for the time shown in Tables 1 and 2.
Dilution with ether and evaporation of the washed 8water)
ether extracts afforded a crude liquid product which was
8m, 3H), 4.60 8d, 1H, Jˆ3.3 Hz), 4.23 8dqd, 1H, Jˆ8.7, 6.3,
3.6 Hz), 3.69 8dd, 1H, Jˆ5.3, 3.3 Hz), 3.44 8s, 3H), 3.38 8q,
1H, Jˆ5.3 Hz), 1.95 8ddd, 1H, Jˆ14.0, 8.7, 5.3 Hz), 1.73
8ddd, 1H, Jˆ14.0, 5.3, 3.6 Hz), 1.24 8d, 3H, Jˆ6.3 Hz); 13C
NMR d 135.51, 132.40, 129.65, 127.78, 101.86, 70.48,
63.43, 56.13, 46.89, 34.56, 20.84.
1
analyzed by H NMR 8Tables 1 and 2). In the case of
The thioethers present in the crude reaction mixture
80.127 g) from epoxide 6 turned out to be not separable by
preparative TLC. Acetylation afforded a crude reaction
mixture 80.142 g, 96% yield), which was subjected to
preparative TLC 8CH2Cl2 was used as the eluant). Extrac-
tion of the two most intense bands afforded the correspond-
ing pure acetylated C-2 80.025g, 17% yield) and C-3
product 80.054 g, 36% yield).
epoxides 5±8, the solvent 8MeCN) was evaporated and
the crude reaction product was ®ltered through a silica gel
pad 8a 7:3 hexane/AcOEt mixture was used as the eluant).
The crude reaction mixture 80.165g) from epoxide 4 was
subjected to preparative TLC 8CH2Cl2 was used as the
eluant). Extraction of the two most intense bands afforded
the corresponding C-3 80.059 g, 36% yield) and C-4 product
80.073 g, 44% yield).
,2)-Methyl 2-,thiophenyl)-3-,O-acetyl)-2,4,6-trideoxy-b-
d-altropyranoside 8C-2 product), a solid, mp 70.5±71.58C
8recrystallized from hexane) 8Found: C, 61.03; H, 6.52.
,1)-Benzyl4-,thiopheny)l-2,4,6-trideoxy- a-d-gulopyrano-
side 8C-4 product), a liquid 8Found: C, 69.18; H, 6.48.
25
25
C15H20O4S requires C, 60.79; H, 6.80): [a]D ˆ266.6 8c
C19H22O3S requires C, 69.06; H, 6.71): [a]D ˆ1100.58 c
1
1.2, CHCl3); H NMR d 7.31±7.50 8m, 2H), 7.09±7.31
1.2, CHCl3); 1H NMR d 7.15±7.45 8m, 10H), 5.04 8dd, 1H,
Jˆ3.6, 1.2 Hz), 4.72 8d, 1H, Jˆ11.8 Hz), 4.52 8d, 1H,
Jˆ11.8 Hz), 4.63 8dq, 1H, Jˆ6.5, 2.2 Hz), 4.09 8dq, 1H,
Jˆ9.3, 2.6 Hz), 3.20±3.29 8m, 1H), 2.46 8dt, 1H, Jˆ14.7,
3.6 Hz), 1.858ddd, Jˆ14.7, 2.6, 1.2 Hz), 1.40 8d, 3H,
8m, 3H), 5.13 8q, 1H, Jˆ3.2 Hz), 4.76 8d, 1H, Jˆ2.1 Hz),
3.87 8dqd, 1H, Jˆ11.1, 6.3, 2.4 Hz), 3.50 8s, 3H), 3.33±3.43
8m, 1H), 1.99 8s, 3H), 1.89±2.03 8m, 1H), 1.50±1.64 8m,
1H), 1.22 8d, 3H, Jˆ6.3 Hz); 13C NMR d 170.48, 135.66,

6090
P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
Jˆ6.5Hz); 13C NMR d 137.65, 136.11, 131.46, 129.74,
129.19, 128.67, 127.35, 98.12, 70.29, 68.87, 61.58, 55.42,
30.97, 19.68 81£Ph signals unresolved).
8. Shelton, J. R.; Cialdella, C. J. Am. Chem. Soc. 1958, 23, 1128±
1133.
9. 8a) Lawton, B. T.; Szarek, W. A.; Jones, J. K. N. Carbohydr.
Res. 1970, 14, 255±258. 8b) Capek, K.; Jary, J. Collect. Czech.
Chem. Commun. 1970, 35, 1727±1732. 8c) Paulsen, H.;
Sum¯eth, B.; Redlich, H. Chem. Ber. 1976, 109, 1362±
1368. 8d) Ohta, K.; Miyagawa, O.; Tsutsui, H.; Mitsunobu,
O. Bull. Chem. Soc. Jpn 1993, 66, 523±535. 8e) Szarek,
W. A.; Vyas, D. M.; Gero, S. D.; Lukacs, G. Can. J. Chem.
1974, 52, 3394±3400.
10. Unlike from previously reported results,9c the dehalogenation
of 81)-30a by means of the Bu3SnH/AIBN protocol led to an
almost 1:1 mixture of diol 81)-31a and chloro diol 32,9e
which turned out to be dif®cult to separate.
,1)-Benzyl3-,thiophen)-y2l,3,6-trideoxy- a-d-glucopyra-
noside 8C-3 product), a liquid 8Found: C, 68.90; H, 6.55.
25
C19H22O3S requires C, 69.06; H, 6.71): [a]D ˆ194.6 8c
1
1.3, CHCl3); H NMR d 7.40±7.53 8m, 2H), 7.21±7.40
8m, 8H), 4.81 8unresolved dd, 1H, Jˆ3.1 Hz), 4.67 8d, 1H,
Jˆ11.9 Hz), 4.44 8d, 1H, Jˆ11.9 Hz), 3.81 8dq, 1H, Jˆ9.0,
6.1 Hz), 3.37 8ddd, 1H, Jˆ13.0, 10.2, 3.8 Hz), 3.04 8ddd,
1H, Jˆ10.2, 9.0, 1.1 Hz), 2.19 8ddd, 1H, Jˆ13.0, 3.8,
0.9 Hz), 1.73 8td, 1H, Jˆ13.0, 3.8 Hz), 1.29 8d, 3H,
Jˆ6.1 Hz); 13C NMR d 138.32, 135.22, 131.42, 129.71,
129.07, 128.96, 128.53, 128.38, 96.53, 74.54, 69.56,
69.36, 48.94, 37.55, 19.02.
11. 8a) Bauer, T. Tetrahedron 1997, 53, 4763±4768. 8b) Kefurt,
Â
K.; Kefurtova, Z.; Jary, J. Collect. Czech. Chem. Commun.
1975, 40, 164±173. 8c) Tsutsui, H.; Mitsunobu, O.
Tetrahedron Lett. 1984, 25, 2159±2162.
12. Brandstetter, H. H.; Zbiral, E. Helv. Chim. Acta 1980, 63,
327±343.
Acknowledgements
Â
This work was supported by the Universita di Pisa and the
Ministero della Universita e della Ricerca Scienti®ca e
Tecnologica 8MURST), Roma. P. C. gratefully acknowl-
edges Merck Research Laboratories for the generous
®nancial support from 2001 ADP Chemistry Award.
13. In search of a stereoselective synthesis of epoxide 81)-7, the
diacetoxy derivative 81)-39a was checked in mono-deprotec-
tion procedures in order to get the monoacetate 40a, regio-
selectively. Unfortunately, the best result obtained 8lipase
PPL, phosphate buffer, pH 7) afforded a mixture of mono-
acetates 34a and 40a showing a regioselectivity 860%)
towards the monoacetate 40a, necessary for the synthesis of
epoxide 81)-7, lower than the corresponding regioselectivity
885%) towards monotosylate 37, found in the monotosylation
of diol 81)-31a, which leads to epoxide 81)-7, as well.
14. Unfortunately, we were not able to obtain the more satisfac-
tory results, recently described.15a As a consequence, our
present results con®rm, in accordance with Jones result, the
decidedly different chemical behavior of anomers 82)-29b
and 81)-29a in the reaction with SO2Cl2,15b and show the
non-applicability of this procedure to an effective synthesis
of diol 82)-31b and, consequently of epoxides 82)-5 and
82)-6 8Scheme 5).
Â
References
1. 8a) Crotti, P.; Di Bussolo, V.; Favero, L.; Macchia, F.;
Pineschi, M. Eur. J. Org. Chem. 1998, 1675±1686 and
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È
3. Martin, A.; Paõs, M.; Monneret, C. Carbohydr. Res. 1983, 113,
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4. Standard reaction conditions: oxirane ring opening reactions
carried out with a nucleophile under proton acid catalysis
8NaN3/NH4Cl in MeOH±H2O, MeOH/H2SO4) or in the
presence of the nucleophile in an appropriate polar solvent
8MeONa in MeOH, NaN3 in DMF, NHEt2 in EtOH, PhSH
in MeOH±NEt3). Chelating reaction conditions: oxirane ring
opening reactions carried out with a nucleophile in the
presence of a metal salt in a polar aprotic solvent 8MeOH/
LiClO4, NaN3/LiClO4 in MeCN, NHEt2/LiClO4 in MeCN,
PhSH/LiClO4 in MeCN).
16. 8a) Garegg, P. J.; Johansson, R.; Ortega, C.; Samuelsson, B.
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233±244.
17. Paulsen, H.; Rutz, V.; Brockhausen, I. Liebigs Ann. Chem.
1992, 747±758.
18. Admitting that an antiparallel 8axial) attack of the nucleophile
8I2) on oxonium ion 41, leading to the axial iodide 42 through
a chair-like transition state 8route a from conformer 410 in
the following scheme) should be preferred with respect to
the corresponding parallel 8equatorial) attack, leading to the
equatorial iodide 42a through a twist-like transition state
8route b from 410), the diastereoisomeric equatorial iodide
42a could be reasonably obtained only by an attack of I2 on
the b face of the intermediate oxonium ion 41, reacting
through its conformer 4100 8route a). However, as tentatively
shown in the following scheme, this attack turns out to be
particularly unfavored because suffering from an 1,3-syn
diaxial interaction with the methyl and the AcO groups in
C85) and C83), respectively. See: 8a) Sayer, J. M.; Yagi, H.;
5. The cis/trans descriptors preceding the number for each
epoxide indicate the relative con®guration between the
oxirane ring and methyl group 8®rst descriptor) and the OR
group 8RˆMe or benzyl) 8second descriptor), respectively.
6. The indifferent use of benzyl or methyl glycosides as deriva-
tives of epoxides 3±8 is dictated by the consideration that the
nature of the acetal group should not reasonably in¯uence the
stereo- and regiochemical behavior of these epoxides.
7. 8a) Fraser-Reid, B.; Kelly, D. R.; Tulshian, D. B.; Ravi, P. S.
J. Carbohydr. Chem. 1983, 2, 105±114. 8b) Brimacombe, J. S.;
Da'Aboul, I.; Tucker, L. C. N. Carbohydr. Res. 1971, 19,
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Chim. Scand. 1993, 47, 889±895.

P. Crotti et al. / Tetrahedron 58 ,2002) 6069±6091
6091
Silverton, J. V.; Friedman, S. L.; Whalen, D. L.; Jerina, D. M.
J. Am. Chem. Soc. 1982, 104, 1972±1978 and references
therein. For related considerations in the cyclohexane system
see: 8b) Eliel, E. L.; Allinger, N. J.; Angyal, S. J.; Morrison,
G. A. ConformationalAnaylsis ; Wiley: New York, 1965; pp
307±314. 8c) Eliel, E. L.; Wilen, S. H. Stereochemistry of
Organic Compounds; Wiley: New York, 1994; pp 729±730.
ably rules out the formation of the diastereoisomeric b-epox-
ide in the oxidation of glycal 8^)-48, in agreement with the
sensitiveness of the DMDO to steric effects. Accordingly, the
attack of the DMDO occurs on the less hindered a-face,
opposite the b-direction of the substituents present in C83)
and C85), to give a-epoxide 8^)-49a, as observed.
25. 8a) Crotti, P.; Di Bussolo, V.; Favero, L.; Macchia, F.;
19. Szarek, W. A.; Zamojski, A.; Gibson, A. R.; Vyas, D. M.;
Jones, J. K. N. Can. J. Chem. 1976, 54, 3783±3793.
Pineschi, M. Gazz. Chim. Ital. 1997, 127, 273±275.
Â
8b) Schaus, S. E.; Branalt, J.; Jacobsen, E. N. J. Org. Chem.
20. Note the completely different regioselectivity observed with
anomeric diols 81)-31a and 82)-31b when subjected to
monoacetylation in the presence of lipase PS: selective protec-
tion of the C82)±OH in the case of 81)-31a and of the C83)±
OH in the case of 82)-31b. Evidently, the axial 8in 31a) or
equatorial direction 8in 31b) of the acetal ±OMe group plays
an important role in favoring or disfavoring the reactivity of
the equatorial C82)±OH group, respectively.
1998, 63, 403±405.
26. Examination of the 1H NMR spectra of epoxides 1±8, and in
particular the values of the coupling constant of the anomeric
proton in 1 and 2 8Jˆ8.6±9.1 Hz)2 and 3 and 4 8Jˆ4.7±
5.0 Hz), as previously observed in the corresponding methyl
glycosides,3 and of the decoupled proton a to the methyl group
in 5±8 8Jˆ10.8±11.2 Hz), clearly indicates for these protons a
preferred equatorial 8in 3 and 4) and an axial orientation 8in 1,
2 and 5±8), respectively, and, consequently, a clear preference
of epoxides 1±8 for the corresponding conformer a with the
methyl group equatorial 8Schemes 8 and 9).2,3
21. Epoxides 5 and 6 have been previously described as a racemic
mixture: Berube, G.; Luce, E.; Jankowski, K. Bull. Soc. Chim.
Fr. 1983, 109±111.
22. In the a-series, the C83)±OH selectivity observed under
Mitsunobu operating conditions led to the epoxide 81)-8,
also obtained through the long monoacetylation±mesyl-
ation±saponi®cation±cyclization procedure starting from
diol 81)-31a. On the contrary, in the b-series, as a result of
the opposite selectivity obtained in the lipase PS-catalyzed
monoacetylation of diol 82)-31b, the Mitsunobu protocol
leads to epoxide 82)-6, the diastereoisomer of epoxide 82)-
5 obtained through the alternative long sequence.
27. Also in the few cases in which the opening reactions under
standard conditions are not completely C-3 stereoselective,
the corresponding results under chelating conditions show
an increase or the only presence of C-3 products, in accor-
dance with the rationalization given.
28. These results would indicate that no chelation can occur
between the oxirane oxygen and the acetalic OR group, if
this makes the epoxide adopt an all axial conformer such as
1b 8from 1) and 5b 8from 5).2
23. Alcohol 8^)-47 was prepared by an hetero Diels±Alder
cycloaddition between Danishefsky diene 845) and acetalde-
hyde. The obtained dihydropyranone 8^)-46 is reduced by
DIBAL to the desired alcohol 8^)-47 8Scheme 6). See:
Danishefsky, S.; Kerwin, Jr., J. F. J. Org. Chem. 1982, 47,
1597±1598 and references therein.
29. Actually, it is not clear why epoxide 6 is not sensitive, to some
extent, to different operating conditions as diastereoisomeric
epoxide 8 is.
30. In accordance with the rationalization given, the results with a
medium strength nucleophile such as NHEt2 determine only a
slight increase of C-2 regioselectivity 8Table 2, entries 33 and
34).
24. The absence in the reaction mixture of products possessing an
inverted con®guration at C82) 8a manno con®guration) reason-