196
2
General Synthetic Methods
2.5 Epoxidation, Dihydroxylation, and Azidonitration of Olefins
Some unsaturated carbohydrates are easily available especially glycals and products derived
from Wittig-type olefinations. The epoxidation and dihydroxylation of these substrates constitutes an important reaction in the synthesis of more complex sugars. Stereocontrolled epoxidation of glycals gives 1,2-epoxy sugars that are useful glycosyl donors [123]. Peroxy acids
cannot generally be used for the epoxidation because of the high reactivity of the 1,2-epoxide which will undergo ring-opening by the acid formed during the course of the epoxidation.
An exception is the m-CPBA-KF mixture ( > Table 7). The addition of potassium fluoride
sufficiently reduces the solubility of m-chlorobenzoic acid to prevent the formation of products arising from epoxide ring-opening [124]. Strictly anhydrous conditions are necessary and
commercial m-CPBA samples have to be further dried. Hereby, high yields of the desired
1,2-epoxy sugars can be obtained. The epoxidation occurs predominately from the α-face of
the olefin placing the oxygen anti to the C3 substituent. Because of the axial C4 substituent,
D-galactal derivatives show an even higher α-selectivity in the epoxidation than the D-glucal derivatives. Another reagent for the epoxidation is dimethyldioxirane [123], which has to
be prepared from acetone and oxone. The byproduct of the epoxidation in this case is acetone which does not react with the product epoxide. As a result, near quantitative yields are
obtained and dimethyldioxirane is often the reagent of choice for epoxidizing glycals [125].
Protected C-methylene pyranosides like 37a,b can be obtained by Wittig methylenation from
the corresponding ketones ( > Scheme 14) [126]. Epoxidation to give the epoxy-branched sugars can now be carried out with a peroxy acid due to the increased stability of the formed
epoxide. The electrophilic attack of the peroxy acid occurs from the less hindered face of the
olefin. In this way, 2-C-methylene pyranosides 37a and 37b undergo epoxidation to give 38a
and 38b, respectively, controlled by the axial anomeric methoxy group [126].
Hex-5-enopyranosides are available by various elimination reactions and can be epoxidized
with m-CPBA and with a dioxirane. Like in the case with glycals the epoxides are quite sensitive to ring-opening reactions. Prolonged treatment with the epoxidizing agent in the presence
of water gives hexos-5-uloses, which can be isolated in moderate to good yields [127]. For
example, hex-5-enopyranoside 39 gives a 7:3 mixture of epoxides 40a,b upon treatment with
⊡ Table 7
Epoxidation of 3,4,6-tri-O-benzyl-D-glucal and -D-galactal
R 1
R 2
Reagent
Yield (%) α/β-ratio Reference
H
OBn m-CPBA, KF
95
9/1
[124]
OBn
H
m-CPBA, KF
95
20/1
[124]
H
OBn Dimethyldioxirane 99
20/1
[123]
OBn
H
Dimethyldioxirane 99
only α
[125]
2
General Synthetic Methods
2.5 Epoxidation, Dihydroxylation, and Azidonitration of Olefins
Some unsaturated carbohydrates are easily available especially glycals and products derived
from Wittig-type olefinations. The epoxidation and dihydroxylation of these substrates constitutes an important reaction in the synthesis of more complex sugars. Stereocontrolled epoxidation of glycals gives 1,2-epoxy sugars that are useful glycosyl donors [123]. Peroxy acids
cannot generally be used for the epoxidation because of the high reactivity of the 1,2-epoxide which will undergo ring-opening by the acid formed during the course of the epoxidation.
An exception is the m-CPBA-KF mixture ( > Table 7). The addition of potassium fluoride
sufficiently reduces the solubility of m-chlorobenzoic acid to prevent the formation of products arising from epoxide ring-opening [124]. Strictly anhydrous conditions are necessary and
commercial m-CPBA samples have to be further dried. Hereby, high yields of the desired
1,2-epoxy sugars can be obtained. The epoxidation occurs predominately from the α-face of
the olefin placing the oxygen anti to the C3 substituent. Because of the axial C4 substituent,
D-galactal derivatives show an even higher α-selectivity in the epoxidation than the D-glucal derivatives. Another reagent for the epoxidation is dimethyldioxirane [123], which has to
be prepared from acetone and oxone. The byproduct of the epoxidation in this case is acetone which does not react with the product epoxide. As a result, near quantitative yields are
obtained and dimethyldioxirane is often the reagent of choice for epoxidizing glycals [125].
Protected C-methylene pyranosides like 37a,b can be obtained by Wittig methylenation from
the corresponding ketones ( > Scheme 14) [126]. Epoxidation to give the epoxy-branched sugars can now be carried out with a peroxy acid due to the increased stability of the formed
epoxide. The electrophilic attack of the peroxy acid occurs from the less hindered face of the
olefin. In this way, 2-C-methylene pyranosides 37a and 37b undergo epoxidation to give 38a
and 38b, respectively, controlled by the axial anomeric methoxy group [126].
Hex-5-enopyranosides are available by various elimination reactions and can be epoxidized
with m-CPBA and with a dioxirane. Like in the case with glycals the epoxides are quite sensitive to ring-opening reactions. Prolonged treatment with the epoxidizing agent in the presence
of water gives hexos-5-uloses, which can be isolated in moderate to good yields [127]. For
example, hex-5-enopyranoside 39 gives a 7:3 mixture of epoxides 40a,b upon treatment with
⊡ Table 7
Epoxidation of 3,4,6-tri-O-benzyl-D-glucal and -D-galactal
R 1
R 2
Reagent
Yield (%) α/β-ratio Reference
H
OBn m-CPBA, KF
95
9/1
[124]
OBn
H
m-CPBA, KF
95
20/1
[124]
H
OBn Dimethyldioxirane 99
20/1
[123]
OBn
H
Dimethyldioxirane 99
only α
[125]