214
2
General Synthetic Methods
ical reduction is usually performed with tributyltin hydride and a catalytic amount of 2,2 -
azobisisobutyronitrile (AIBN) and goes through the formation of a glycosyl radical which is
stabilized by the endocyclic oxygen [213]. The radical reduction at C1 can also be carried
out with titanocene borohydride which can be prepared from titanocene dichloride and sodium borohydride [214]. Furthermore, radical reductions can be achieved with protected aldoses
containing a phenyl thionocarbonate at C1 [215]. Because of the toxicity of organotin compounds this reduction has been performed with a catalytic amount of tributyltin hydride in the
presence of polymethylhydrosiloxane as the stoichiometric reductant [215].
Other methods for preparing 1,5-anhydroalditols employ lithium aluminum hydride reduction of protected 1,2-epoxy pyranoses and glycosyl halides. For example, the reductive ringopening of the glucose-derived epoxide in > Table 7 affords 1,5-anhydro-3,4,6-tri-O-benzylD-glucitol in 74% yield [216] while the reduction of 2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl
bromide gives 1,5-anhydro-L-rhamnitol in 87% yield [217]. Additionally, anhydroalditols can
also be prepared by Raney nickel-mediated desulfurization of thioglycosides [218] while the
same reduction on aldose dialkyl dithioacetals gives rise to 1-deoxyalditols [219].
4.2 Deoxygenation of Primary Alcohols
Diisopropylidenegalactopyranose 7 has been deoxygenated at C6 under various conditions
which illustrates some of the methods that are available for removing a primary alcohol
( > Table 13). Sulfonates can be selectively introduced at the primary position in many carbohydrates and can be displaced by a hydride from either lithium aluminum hydride or
sodium borohydride. Besides galactose the reduction has also been applied for removing
primary sulfonates in glucose [230], mannose [231], and ribose [232]. Carboxylates, on
the other hand, are not displaced by hydride, but can be removed by photolysis at 254 nm
in an aqueous hexamethylphosphoric triamide (HMPA) solution [223]. The reaction goes
through a radical mechanism and does not tolerate halides and other carbonyl groups in the
substrate [233].
A more common radical reaction for deoxygenating alcohols is the Barton–McCombie reaction [234]. In this transformation the alcohol is converted into a thiocarbonyl derivative (xanthate, thionocarbonate, or thionocarbamate) which undergoes homolytic C-OCS cleavage upon
treatment with tributyltin hydride and a radical initiator. In the original Barton–McCombie
procedure secondary alcohols are treated with N,N -thiocarbonyldiimidazole or carbon disulfide/methyl iodide/sodium hydride and the resulting thionocarbamate or xanthate is then reductively cleaved with tributyltin hydride [234]. However, these procedures proved inefficient for
deoxygenating primary alcohols due to the slightly lower stability of a primary radical as
compared to a secondary radical [234,235]. Instead, improved conditions for primary alcohols have been developed by acylation with 2,4,6-trichlorophenyl or 4-fluorophenyl chlorothionoformate followed by deoxygenation of the resulting thionocarbonate [224]. Although tributyltin hydride is an effective reducing agent which is compatible with esters, ethers, acetals,
and olefins, organotin compounds are toxic and difficult to remove completely from the desired
products. Furthermore, tributyltin hydride is rather expensive and has a limited shelf-stability.
Therefore, alternative reagents have been investigated and particular attention has been given
to hydrogen donors containing Si–H or P–H bonds [236]. So far, the most effective tin hydride
2
General Synthetic Methods
ical reduction is usually performed with tributyltin hydride and a catalytic amount of 2,2 -
azobisisobutyronitrile (AIBN) and goes through the formation of a glycosyl radical which is
stabilized by the endocyclic oxygen [213]. The radical reduction at C1 can also be carried
out with titanocene borohydride which can be prepared from titanocene dichloride and sodium borohydride [214]. Furthermore, radical reductions can be achieved with protected aldoses
containing a phenyl thionocarbonate at C1 [215]. Because of the toxicity of organotin compounds this reduction has been performed with a catalytic amount of tributyltin hydride in the
presence of polymethylhydrosiloxane as the stoichiometric reductant [215].
Other methods for preparing 1,5-anhydroalditols employ lithium aluminum hydride reduction of protected 1,2-epoxy pyranoses and glycosyl halides. For example, the reductive ringopening of the glucose-derived epoxide in > Table 7 affords 1,5-anhydro-3,4,6-tri-O-benzylD-glucitol in 74% yield [216] while the reduction of 2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl
bromide gives 1,5-anhydro-L-rhamnitol in 87% yield [217]. Additionally, anhydroalditols can
also be prepared by Raney nickel-mediated desulfurization of thioglycosides [218] while the
same reduction on aldose dialkyl dithioacetals gives rise to 1-deoxyalditols [219].
4.2 Deoxygenation of Primary Alcohols
Diisopropylidenegalactopyranose 7 has been deoxygenated at C6 under various conditions
which illustrates some of the methods that are available for removing a primary alcohol
( > Table 13). Sulfonates can be selectively introduced at the primary position in many carbohydrates and can be displaced by a hydride from either lithium aluminum hydride or
sodium borohydride. Besides galactose the reduction has also been applied for removing
primary sulfonates in glucose [230], mannose [231], and ribose [232]. Carboxylates, on
the other hand, are not displaced by hydride, but can be removed by photolysis at 254 nm
in an aqueous hexamethylphosphoric triamide (HMPA) solution [223]. The reaction goes
through a radical mechanism and does not tolerate halides and other carbonyl groups in the
substrate [233].
A more common radical reaction for deoxygenating alcohols is the Barton–McCombie reaction [234]. In this transformation the alcohol is converted into a thiocarbonyl derivative (xanthate, thionocarbonate, or thionocarbamate) which undergoes homolytic C-OCS cleavage upon
treatment with tributyltin hydride and a radical initiator. In the original Barton–McCombie
procedure secondary alcohols are treated with N,N -thiocarbonyldiimidazole or carbon disulfide/methyl iodide/sodium hydride and the resulting thionocarbamate or xanthate is then reductively cleaved with tributyltin hydride [234]. However, these procedures proved inefficient for
deoxygenating primary alcohols due to the slightly lower stability of a primary radical as
compared to a secondary radical [234,235]. Instead, improved conditions for primary alcohols have been developed by acylation with 2,4,6-trichlorophenyl or 4-fluorophenyl chlorothionoformate followed by deoxygenation of the resulting thionocarbonate [224]. Although tributyltin hydride is an effective reducing agent which is compatible with esters, ethers, acetals,
and olefins, organotin compounds are toxic and difficult to remove completely from the desired
products. Furthermore, tributyltin hydride is rather expensive and has a limited shelf-stability.
Therefore, alternative reagents have been investigated and particular attention has been given
to hydrogen donors containing Si–H or P–H bonds [236]. So far, the most effective tin hydride