Reactions at Oxygen Atoms
2.1
147
tert-Butyldimethylsilyl pentenyl ether is also a suitable reagent for efficient silylation of primary and secondary hydroxyl groups ( > Scheme 52b). Activation is carried out with iodonium
di-sym-collidine perchlorate (IDCP) and this procedure can be applied even to pentenyl glycosides [296].
An unusual way for the preparation of TBS ethers involves the reaction of diethylboronyl
ethers, obtained by the reaction of the corresponding alcohol with BEt 3 , with the TBDMS-enolate of pentane-2,4-dione in the presence of a catalytic amount of TMSOTf ( > Scheme 52c)
[297].
The palladium(0) nanoparticle-catalyzed silylation of sugars by silane alcoholysis of tert-butyldimethylsilane has been proposed as an attractive alternative to the established silyl chloride
method. The methodology gives convenient access to the 3,6-silylated methyl glycopyranosides as the dominant products rather than the 2,6-silylated glycosides typically obtained by the
silyl chloride method [298]. Changing to homogeneous cationic catalysts of iridium and rhodium, 2,3,6- and 2,4,6-trisilylated derivatives are obtained in synthetically useful yields [299].
The TBDMS group has also been introduced [300] to alcohols or phenols by the Mitsunobu
reaction (DEAD/PPh 3 , THF, −78 °C) using tert-butyldimethylsilanol.
Numerous methods are now available in the literature for the deprotection of TBS ethers under
a variety of conditions. One of the most effective ways for the cleavage of silyl ethers is based
on the exploitation of the high affinity of silicon towards fluoride ions. Thus, a number of
reagents involving one form of fluoride or another, such as tetrabutylammonium fluoride [292],
BF 3 ·Et 2 O [301], hydrofluoric acid [302], fluorosilicic acid [303], ammonium fluoride [304],
silicon fluoride [305], lithium tetrafluoroborate [306], and chlorotrimethylsilane/potassium fluoride dehydrate [307] have been developed for the deprotection of TBDMS ethers. Among
these, TBAF is most frequently used but the strong basicity of the fluoride anion makes it
inappropriate for base sensitive functionalities.
Similarly, acidic reagents such as HCl [308], H 2 SO 4 [309], PPTS [310], TFA [311], TsOH
[312] etc., have also been employed for this purpose but cannot be used in the presence of
acid-sensitive functionalities. This has led to the development of several Lewis acids and other
reagents including BF 3 ·OEt 2 [313], BCl 3 [314], Sc(OTf) 3 [315], Ce(OTf) 4 [316], InCl 3 [317],
ZnBr 2 [318], Zn(BF 4 ) 2 [319], CeCl 3 –NaI [320], BiBr 3 [321], BiOClO 4 [322], Cs 2 CO 3 [323],
CBr 4 –MeOH [324], I 2 [325] and CAN [326] for desilylation.
Recently, an environmentally benign phosphomolybdic acid supported on silica gel has
been used for the chemoselective deprotection of TBS ethers in carbohydrate derivatives
( > Scheme 53). The mild conditions are compatible with the presence of other protecting
groups such as isopropylidene acetal, OTBDPS, OTHP, OAllyl, OBn, OAc, OBz, N-BOc,
N-CBz, and N-Fmoc which are stable under the reaction conditions. Another advantage of
this procedure is that the catalyst can be readily recovered and recycled [327].
2.5.3 tert -Butyldiphenylsilyl (TBDPS) Group
The TBDPS group was introduced by Hanessian and Lavallee in 1975 [328]. The TBDPS
group has greater steric demands than the TBS group and, therefore can result in much more
selective protections of hydroxyl groups. The group is also less prone to migrate to proximate
hydroxyl groups under neutral or acidic conditions than the TBS group but it may migrate
under basic conditions [329].
2.1
147
tert-Butyldimethylsilyl pentenyl ether is also a suitable reagent for efficient silylation of primary and secondary hydroxyl groups ( > Scheme 52b). Activation is carried out with iodonium
di-sym-collidine perchlorate (IDCP) and this procedure can be applied even to pentenyl glycosides [296].
An unusual way for the preparation of TBS ethers involves the reaction of diethylboronyl
ethers, obtained by the reaction of the corresponding alcohol with BEt 3 , with the TBDMS-enolate of pentane-2,4-dione in the presence of a catalytic amount of TMSOTf ( > Scheme 52c)
[297].
The palladium(0) nanoparticle-catalyzed silylation of sugars by silane alcoholysis of tert-butyldimethylsilane has been proposed as an attractive alternative to the established silyl chloride
method. The methodology gives convenient access to the 3,6-silylated methyl glycopyranosides as the dominant products rather than the 2,6-silylated glycosides typically obtained by the
silyl chloride method [298]. Changing to homogeneous cationic catalysts of iridium and rhodium, 2,3,6- and 2,4,6-trisilylated derivatives are obtained in synthetically useful yields [299].
The TBDMS group has also been introduced [300] to alcohols or phenols by the Mitsunobu
reaction (DEAD/PPh 3 , THF, −78 °C) using tert-butyldimethylsilanol.
Numerous methods are now available in the literature for the deprotection of TBS ethers under
a variety of conditions. One of the most effective ways for the cleavage of silyl ethers is based
on the exploitation of the high affinity of silicon towards fluoride ions. Thus, a number of
reagents involving one form of fluoride or another, such as tetrabutylammonium fluoride [292],
BF 3 ·Et 2 O [301], hydrofluoric acid [302], fluorosilicic acid [303], ammonium fluoride [304],
silicon fluoride [305], lithium tetrafluoroborate [306], and chlorotrimethylsilane/potassium fluoride dehydrate [307] have been developed for the deprotection of TBDMS ethers. Among
these, TBAF is most frequently used but the strong basicity of the fluoride anion makes it
inappropriate for base sensitive functionalities.
Similarly, acidic reagents such as HCl [308], H 2 SO 4 [309], PPTS [310], TFA [311], TsOH
[312] etc., have also been employed for this purpose but cannot be used in the presence of
acid-sensitive functionalities. This has led to the development of several Lewis acids and other
reagents including BF 3 ·OEt 2 [313], BCl 3 [314], Sc(OTf) 3 [315], Ce(OTf) 4 [316], InCl 3 [317],
ZnBr 2 [318], Zn(BF 4 ) 2 [319], CeCl 3 –NaI [320], BiBr 3 [321], BiOClO 4 [322], Cs 2 CO 3 [323],
CBr 4 –MeOH [324], I 2 [325] and CAN [326] for desilylation.
Recently, an environmentally benign phosphomolybdic acid supported on silica gel has
been used for the chemoselective deprotection of TBS ethers in carbohydrate derivatives
( > Scheme 53). The mild conditions are compatible with the presence of other protecting
groups such as isopropylidene acetal, OTBDPS, OTHP, OAllyl, OBn, OAc, OBz, N-BOc,
N-CBz, and N-Fmoc which are stable under the reaction conditions. Another advantage of
this procedure is that the catalyst can be readily recovered and recycled [327].
2.5.3 tert -Butyldiphenylsilyl (TBDPS) Group
The TBDPS group was introduced by Hanessian and Lavallee in 1975 [328]. The TBDPS
group has greater steric demands than the TBS group and, therefore can result in much more
selective protections of hydroxyl groups. The group is also less prone to migrate to proximate
hydroxyl groups under neutral or acidic conditions than the TBS group but it may migrate
under basic conditions [329].