Chlorotrimethylsilane, alcohol protection

One of the more common methods of alcohol protection is by reaction with a chlorotrialkylsilane, CI-S1R3, to yield a trialkylsilyl ether, R -O-SilTj. Chlorotrimethylsilane is often used, and the reaction is carried out in the presence of a base, such as tciethylamine, to help form the alkoxide anion from the alcohol and to remove the HC1 by-product from the reaction. 

We can also easily convert hydroxyl groups to silyl ethers. Section 14-10B covered the use of the triisopropylsilyl (TIPS) protecting group for alcohols. Similarly, sugars can be converted to their silyl ethers by treatment with a silyl chloride, such as chlorotrimethylsilane (TMSC1), and a tertiary amine, such as triethylamine. 

Chlorotrimethylsilane, (CH3)3SiCl Reacts with alcohols to add the trimethylsilyl protecting group (Section 17.8). 

The trimethylsilyl group was the first to be developed and is widely used for the protection of serine and threonine (Table 6). Chlorotrimethylsilane, l,14 3,3,3-hexamethyldisilazane, and A(0-bis(trimethylsilyl)acetamide are commercially available reagents used for the conversion of alcohols into the corresponding trimethylsilyl derivatives.Furthermore, trimethylsilyl cyanide has been used to protect the side chains of serine, threonine, and ty-rosine.f This silyl protection allows the formation of A -carboxyanhydrides from H-Ser(TMS)-OH and H-Thr(TMS)-OH, and their application in peptide synthesis in the aqueous phase.f l The TMS group can be removed under various conditions, depending on the kind of functional group to which it is bound the TMS ethers are more stable than related amino or carboxy derivatives.These differences in stability allow the direct application of completely silylated hydroxy amino acids in peptide synthesis.b ... 

The possibility of carrying out Mannich reactions with cyclic aminol ethers has been alluded to earlier. It has so been shown that the in situ method using chlorosilanes can be applied to oxazolidines such as 3-methyl-1,3-oxazolidine. The ring-chain tautomerlsm of 1,3-oxazolidines in the presence of protlc acids has been studied by NMR spectroscopy and the hydroxy Schiff base oxazolidine tautomerlsm has been discussed in terms of the apparent violation of Baldwin s rules. The idea that a Mannich reaction could be carried out while at the same time protecting the resulting alcoholic function was explored in a reaction of 2-methylfuran with 3-methyl-1,3-oxazolidine and f-butyldimethylchlorosilane. The yield in this reaction is only modest (33%) but catalysis with 1,2,4-triazole results in an improvement to 61% (equation 30). Go yields are obtained in reactions of 2-methylfuran with 3-methyl-1,3-oxazolidine and chlorotrimethylsilane (73%) or trichloromethylsilane (87%). Even the reaction of furan gives a good yield (75%) with trichloromethylsilane. 

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