Protection chlorotrimethylsilane

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. 

A. 1-Trimethylsilyloxycyclohexene. In a 500-ml. three-necked, round-bottomed flask fitted with a mechanical stirrer, a reflux condenser protected with a calcium chloride tube, and a rubber septum are placed 100 ml. of N,Af-dimethylformamide (Note 1) and 60.6 g. (0.60 mole) of triethylamine (Note 2). The solution is stirred while 32.6 g. (0.30 mole) of chlorotrimethylsilane (Note 3) and 24.5 g. (0.25 mole) of cyclohexanone are injected in succession through the septum into the flask. The resulting mixture is stirred and heated under reflux for 6 hours, cooled to room temperature,... 

The diol function of 130 was protected as its acetonide 131 (88 %). Next, the enone function was installed by a-selenation of the enoxysilane, followed by peroxide oxidation and elimination (57 % over two steps). Finally, the unsaturated ketone 132 was homologated by 1,4-addition of trimethylsilylmethyl magnesium chloride, trapping with chlorotrimethylsilane, and reoxidation, to afford the target 117 (88 %). 

Due to the extremely low nucleophilicity of the imino group, 187,188 acylation of thiazolidine-4-carboxylic acid (11) is not a trivial procedure. In fact, N-protected Thz derivatives can be prepared by standard procedures, but strong acylating conditions are required. The related N-Boc derivative is obtained only by prolonged reaction times with Boc-N3 U2,189 or with Boc20. 113 For preparation of the N-Z derivative, silylation of Thz with, for example, chlorotrimethylsilane is recommended prior to the reaction benzyl chloroformate. 200 Due to the stability of thiazolidine-4-carboxylic acid to acids its methyl ester is obtained by HC1 catalyzed reaction with methanol, 190 whereas the amide is formed by reacting Thz N-carboxyanhydride with ammonia.1 89 Derivatives of thiazolidine-4-carboxylic acid are listed in Table 8. 

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. 

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of carbonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into O-TRIMETHYLSILYL-4-METHOXYMANDELO-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotrimethylsilane. A general synthesis of altenic esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADIENOATE. 

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

Protection of an enone as the dithiane derivative without destruction of an accompanying dioxane was accomplished during a synthesis of Aphidicolin [Scheme 2.90]181 by using the hw-trimethylsilyl ether of propane- 1,3-dithiol in the presence of zinc iodide as the catalyst.182 In the same vein, a synthesis of a fully functionalised B-ring system of Taxol [Scheme 2.91] included the selective thio ace tali sat ion of an aldehyde in the presence of a ketone using silver(I)-cata-lysed thioacetalisation with EtS-TMS and chlorotrimethylsilane.183... 

When l,l,2-triphenylethane-l,2-diol-derived esters are submitted to a monodeprotonation and subsequently treated with Chlorotrimethylsilane, the formation of 2-trimethylsilyloxy-l,3-dioxolanes results. The orthoester moiety thus obtained serves as a protecting group for carboxylic acids (eq 3) it is stable towards alkyllithium reagents and can be cleaved under nonacidic conditions by alkaline hydrolysis. ... 

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 ... 

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