Silyl Ethers as Protecting Groups

Silyl Ethers as Protective Groups for Alcohols. Oxidative Deprotection and Stability Under Alcohol Oxidation Conditions, Muzart. J. Synthesis. 1993, 11... 

The synthetic potential of silyl ethers as protecting groups for hydroxyls is based on the fact that they can be easily introduced and cleaved under mild conditions and their relative stability can be tuned by varying the substituents on silicon. In carbohydrate chemistry, the tert-butyl-dimethylsilyl (TBDMS), terl-butyldiphenylsilyl (TBDPS) and triethyl-silyl (TES) ethers are the most often applied silicon-based protecting groups (Scheme 2.9).23... 

The use of silyl ethers as protecting groups for the hydroxyl functionality is well known, and their adaption into linker units was a welcome addition to the SPOS literature. Thus, many silyl linker units have been reported for alcohols, and a selection is illustrated in Table 1.15. Owing to the large number of reported examples, a complete discussion of each is beyond the scope of this chapter, but Spivey has written a complete review. Much like deprotection of their solution-phase counterparts, cleavage from silyl linkers can be achieved using, for example, HE (Table 1.15, Entries 1-3 and 6) , TBAF (Table 1.15, Entries AcOH (Table 1.15, Entries 1 and 4) °, or TEA (Table 1.15,Entry 5). Beyond alcohols, other traditional sUyl linker units are useful for SPOS with other substrates such as amines (Table 1.15, Entry... 

Silyl Ethers.—Examples of the usefulness of t-butyldimethylsilyl ethers as protecting groups are nicely illustrated in Schemes 17 and 19. Methyl a-D-gluco-pyranoside reacted with a molar equivalent of t-butyldimethylsilyl chloride in pyridine to give the 6-0-(t-butyldimethylsilyl) derivative in virtually quantitative yield, and sucrose reacted with 3.5 molar equivalents of the silylating reagent to give almost exclusively r,6,6 -tri-0-(t-butyldimethylsilyl)sucrose and traces of mono- and di-substituted products. In the presence of an excess of sucrose, a mixture of 6 -, 6,6 -di-, and r,6,6 -tri-0-(t-butyldimethylsilyl)sucroses was obtained. 

A class of photolabile linkers has been developed to circumvent the use of silyl ethers as linkers and allow for the use of temporary silyl protecting groups.34,35 Photolabile linkers, such as 2, often involve the use of o-nitrobenzyl ether groups. This functional group is stable to a variety of conditions however, cleavage from the polymer support is often slow and... 

Lalonde, M. and Chan, T.H. (1985). Use of organosilicon reagents as protective groups in organic synthesis. Synthesis, 817-845. Brownbridge, P. (1983). Silyl enol ethers in synthesis. Synthesis, 1-28 and 85-104. ... 

Silyl ethers are ethers with a substituted silicon atom replacing one of the alkyl groups of an ether. Silyl ethers share some of the properties of ethers (resistant to some acids, bases, and oxidizing agents), but they are more easily formed and more easily hydrolyzed. These properties make them useful as protecting groups, and silyl ethers are frequently used to protect alcohols. 

Q Additional coverage on silyl ethers addresses their use as protecting groups for alcohols and carbohydrates. 

A new section covers the formation and cleavage of silyl ethers, and their strategy and use as protecting groups on alcohols. This new material introduces the concept of... 

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