148
2
General Synthetic Methods
⊡ Scheme 53
The ring oxygen is missing in the fructose derivatives
⊡ Scheme 54
Selective removal of TBDPS ethers in the presence of TBS ethers
The TBDPS ethers are prepared by treating alcohols with TBDPS-Cl in DMF in the presence
of imidazole (the primary hydroxy group reacts faster than the secondary one). Tertiary alcohols do not silylate. The silylation of hindered alcohols is greatly accelerated with the aid of
AgNO 3 , NH 4 NO 3 , or NH 4 ClO 4 [330].
TBDPS ethers are generally cleaved under the same acidic conditions as those used for TBS
ethers but longer reaction times are necessary and consequently selective removal of TBS
groups in the presence of TBDPS groups is very common [331,332]. The electron-withdrawing
effect of the phenyl substituents enhances the electrophilicity of the silicon atom and therefore
is more susceptible towards nucleophiles. For this reason it is possible to reverse the tendency
of TBS ethers to cleave more easily than TBDPS ethers using ion fluoride or basic hydrolysis [333]. Some examples in glycal derivatives are shown in > Scheme 54.
2.5.4 Triisopropylsilyl (TIPS) Group
The TIPS group [334] is one of the most sterically hindered silyl protecting groups, being
removed only slowly under standard acid- or base-catalyzed hydrolysis conditions. The large
steric bulk ensures high selectivity in the protection of primary hydroxyl groups over sec-
2
General Synthetic Methods
⊡ Scheme 53
The ring oxygen is missing in the fructose derivatives
⊡ Scheme 54
Selective removal of TBDPS ethers in the presence of TBS ethers
The TBDPS ethers are prepared by treating alcohols with TBDPS-Cl in DMF in the presence
of imidazole (the primary hydroxy group reacts faster than the secondary one). Tertiary alcohols do not silylate. The silylation of hindered alcohols is greatly accelerated with the aid of
AgNO 3 , NH 4 NO 3 , or NH 4 ClO 4 [330].
TBDPS ethers are generally cleaved under the same acidic conditions as those used for TBS
ethers but longer reaction times are necessary and consequently selective removal of TBS
groups in the presence of TBDPS groups is very common [331,332]. The electron-withdrawing
effect of the phenyl substituents enhances the electrophilicity of the silicon atom and therefore
is more susceptible towards nucleophiles. For this reason it is possible to reverse the tendency
of TBS ethers to cleave more easily than TBDPS ethers using ion fluoride or basic hydrolysis [333]. Some examples in glycal derivatives are shown in > Scheme 54.
2.5.4 Triisopropylsilyl (TIPS) Group
The TIPS group [334] is one of the most sterically hindered silyl protecting groups, being
removed only slowly under standard acid- or base-catalyzed hydrolysis conditions. The large
steric bulk ensures high selectivity in the protection of primary hydroxyl groups over sec-