Oxidation, Reduction, and Deoxygenation
2.2
191
Trifluoroacetic anhydride (TFAA) is also a very potent activator for DMSO and concomitant
trifluoroacetylation of the starting alcohol is usually not observed [27]. Both the Swern and
the TFAA procedure are carried out at low temperature to prevent undesired side reactions,
particularly formation of the methylthiomethyl ether. Before these two methods became
developed, acetic anhydride was often used for DMSO activation. However, the oxidation under these conditions is slower and the methylthiomethyl ether byproduct is often
observed [27].
Among the chromium(VI) oxides PCC [28,89] and PDC [28,40] are preferred for oxidation
of carbohydrate secondary alcohols. The reaction is in both cases accelerated by molecular
sieves [90] and anhydrous acetic acid [91]. Activation of PDC can also be achieved with acetic
anhydride [40]. The most widely used procedure, however, seems to be PCC and 3 Å molecular sieves in dichloromethane [28,92]. PCC is mildly acidic, but acetal protecting groups
remain stable to the oxidation conditions. Chromium(VI) oxide-pyridine complex is usually
not a satisfactory oxidant for carbohydrate secondary alcohols. However, further activation by
acetic anhydride gives good yields of ketones with 4 equiv. of reagent [20]. Secondary alcohols
in thioglycosides can be oxidized under these conditions without accompanying oxidation at
sulfur [93].
If a secondary alcohol is not easily oxidized by other methods the ruthenium(VIII) oxide catalyzed procedure is often recommended. As mentioned previously, this is a strong oxidation
method which is not compatible with a number of functional groups. Sodium periodate usually serves as the stoichiometric oxidant, but sodium hypochlorite has also been used in the
oxidation of secondary alcohols [94]. Because of the cheap oxidants and a straightforward
work-up this reaction is well suited for large-scale oxidations [95]. The TEMPO procedure
also employs a cheap stoichiometric oxidant and has been applied in the oxidation of 23 on
a kilogram scale [87]. The TPAP-catalyzed method is a milder procedure and many functional
groups are stable to these conditions. However, secondary alcohols are still oxidized to ketones
in high yield with NMO as the co-oxidant [24].
The Dess–Martin periodinane [31] has also been used for oxidation of carbohydrate secondary alcohols [88,96]. Oxidations are usually carried out under neutral conditions in
dichloromethane, chloroform, or acetonitrile. However, the Dess–Martin periodinane is used
stoichiometrically and as such becomes a rather expensive oxidant. As a result, it is mostly
recommended for special cases where the above-described procedures are insufficient.
Manganese(IV) oxide is very slow at oxidizing isolated secondary alcohols. However, if the
alcohol is allylic or alpha to a lactone manganese(IV) oxide is the reagent of choice [3,97].
The reagent has to be activated for the oxidation and a commercial sample is usually not sufficient. Activated manganese(IV) oxide is prepared as a solid from potassium permanganate and
manganese(II) sulfate [98]. Oxidations can be carried out in a variety of solvents, but ether,
chloroform, or acetone are usually good choices. Hereby, allylic alcohol 25 and α-hydroxylactone 27 undergo oxidation in high yield ( > Scheme 9) [99,100].
Manganese(IV) oxide will also oxidize the C3 hydroxy group in glycals [101]. However,
a variety of other oxidants has also been applied for this special case ( > Table 5). Silver carbonate on Celite is a mild and neutral oxidant that also gives good yields for allylic oxidations.
Because of the heterogeneous reaction conditions, an excess (5 equiv. or more) of this reagent
is needed [102]. Fully protected glycals can be oxidized directly with N-bromosuccinimide
(NBS)/benzoyl peroxide [105] or with the Koser reagent (PhI(OH)OTs) [106].
2.2
191
Trifluoroacetic anhydride (TFAA) is also a very potent activator for DMSO and concomitant
trifluoroacetylation of the starting alcohol is usually not observed [27]. Both the Swern and
the TFAA procedure are carried out at low temperature to prevent undesired side reactions,
particularly formation of the methylthiomethyl ether. Before these two methods became
developed, acetic anhydride was often used for DMSO activation. However, the oxidation under these conditions is slower and the methylthiomethyl ether byproduct is often
observed [27].
Among the chromium(VI) oxides PCC [28,89] and PDC [28,40] are preferred for oxidation
of carbohydrate secondary alcohols. The reaction is in both cases accelerated by molecular
sieves [90] and anhydrous acetic acid [91]. Activation of PDC can also be achieved with acetic
anhydride [40]. The most widely used procedure, however, seems to be PCC and 3 Å molecular sieves in dichloromethane [28,92]. PCC is mildly acidic, but acetal protecting groups
remain stable to the oxidation conditions. Chromium(VI) oxide-pyridine complex is usually
not a satisfactory oxidant for carbohydrate secondary alcohols. However, further activation by
acetic anhydride gives good yields of ketones with 4 equiv. of reagent [20]. Secondary alcohols
in thioglycosides can be oxidized under these conditions without accompanying oxidation at
sulfur [93].
If a secondary alcohol is not easily oxidized by other methods the ruthenium(VIII) oxide catalyzed procedure is often recommended. As mentioned previously, this is a strong oxidation
method which is not compatible with a number of functional groups. Sodium periodate usually serves as the stoichiometric oxidant, but sodium hypochlorite has also been used in the
oxidation of secondary alcohols [94]. Because of the cheap oxidants and a straightforward
work-up this reaction is well suited for large-scale oxidations [95]. The TEMPO procedure
also employs a cheap stoichiometric oxidant and has been applied in the oxidation of 23 on
a kilogram scale [87]. The TPAP-catalyzed method is a milder procedure and many functional
groups are stable to these conditions. However, secondary alcohols are still oxidized to ketones
in high yield with NMO as the co-oxidant [24].
The Dess–Martin periodinane [31] has also been used for oxidation of carbohydrate secondary alcohols [88,96]. Oxidations are usually carried out under neutral conditions in
dichloromethane, chloroform, or acetonitrile. However, the Dess–Martin periodinane is used
stoichiometrically and as such becomes a rather expensive oxidant. As a result, it is mostly
recommended for special cases where the above-described procedures are insufficient.
Manganese(IV) oxide is very slow at oxidizing isolated secondary alcohols. However, if the
alcohol is allylic or alpha to a lactone manganese(IV) oxide is the reagent of choice [3,97].
The reagent has to be activated for the oxidation and a commercial sample is usually not sufficient. Activated manganese(IV) oxide is prepared as a solid from potassium permanganate and
manganese(II) sulfate [98]. Oxidations can be carried out in a variety of solvents, but ether,
chloroform, or acetone are usually good choices. Hereby, allylic alcohol 25 and α-hydroxylactone 27 undergo oxidation in high yield ( > Scheme 9) [99,100].
Manganese(IV) oxide will also oxidize the C3 hydroxy group in glycals [101]. However,
a variety of other oxidants has also been applied for this special case ( > Table 5). Silver carbonate on Celite is a mild and neutral oxidant that also gives good yields for allylic oxidations.
Because of the heterogeneous reaction conditions, an excess (5 equiv. or more) of this reagent
is needed [102]. Fully protected glycals can be oxidized directly with N-bromosuccinimide
(NBS)/benzoyl peroxide [105] or with the Koser reagent (PhI(OH)OTs) [106].