Silyl protecting groups trimethylsilyl

Silyl protecting groups are the gold standard for the protection of alcohols.234 Novel photochemically removable protection groups for alcohols have been developed by Brook et a/.23S and Pirrung et al,236 For instance, cyclo-pentanol can be reacted with tris(trimethylsilyl)chlorosilane 53 in the presence of a mild base to yield the protected silyl ether 54. The protection group can be removed conveniently upon UV irradiation or by the use of Bu4NF (Scheme 12). 

In the first example, nitration of the benzoate (140) with nitric acid affords the nitro derivative. Hydrogenation converts this to the anthranilate (141). In one of the standard conditions for forming quinazolones, that intermediate is then treated with ammonium formate to yield the heterocycle (142). Reaction of 142 with phosphorus oxychloride leads to the corresponding enol chloride (143). Condensation of 143 with m-iodoaniline (144) leads to displacement of chlorine and consequent formation of the aminoquinazoline (145). Reaction with the trimethylsilyl derivative of acetylene in the presence of tetrakis-triphenylphosphine palladium leads to replacement of iodine by the acetylide. Tributylammonium fluoride then removes the silyl protecting group to afford the kinase inhibitor erlotinib (146). ... 

Synthesis from o-arabinose D-Arabinose has been used for the synthesis of 13-lactam and 1-oxacephem antibiotics (Scheme 9). Thus, the bicyclic 3-lactam 85, obtained from 3,4-di-(9-trimethylsilyl-D-arabinal (84), was treated with zcrz-butyl glyoxylate to prcxluce 86, which underwent chlorination using thionyl chloride to afford 87. Treatment of 87 with triphenylphosphine followed by removal of the silyl protecting groups afforded the diol 88. Pericxlate oxidation of 88 in the presence of ammonium sulfate afforded 90 via 89. Subsequent reduction of 90 with scxUum borohydride followed by acetylation afforded the lactams 91 and 92. 

Much attention has been devoted to the conversion of aldehydes into the trimethylsilyl ethers of (a-hydroxyalkyl)-phosphonic acids 210 or analogous -phosphinic acids, or of the corresponding (a-hydroxyalkyl)phosphonic diamides 211 by the use of dialkyl trimethylsilyl phosphite or Me3SiOP(NEt2)2 (or other phosphorodiamidite) It is a reaction which occurs very readily, even at room temperature, and the ready methanolytic or hydrolytic removal of the silyl protecting group makes the procedure an attractive alternative to the direct synthesis of the (a-hydroxyalkyl)phosphonic acids from dialkyl hydrogenphosphonates and carbonyl compounds. Silyl-protected hydroxy-phosphonic and -phosphinic acid derivatives are useful for further synthetic development. ... 

The foundation for the use of the tris(trimethylsilyl)silyl protecting group was laid by Brook and coworkers, who reported protocols for the introduction and removal of this group [291, 292]. While reactions of alcohols with tris (trimethylsilyl)silyl halides in the presence of a base are most commonly employed, Ottosson and coworkers provided an interesting acid catalyzed protocol (Scheme 30) [293]. 

In a quite different approach, shown in Scheme 204, cycloaddition of nitrile 1232 to trimethylsilyldiazomethane provides silylated triazole 1233, isolated in 75% yield. Treatment with tetrabutylammonium fluoride removes the trimethylsilyl group and simultaneously the silyl protection of the carboxylic group to afford 4-substituted triazole derivative 1234 in 81% yield <2003PEN699>. 

The phosphitylation procedure activated by tetrazole led to the phosphite structure (step a) which was effectively oxidized by TBHP to yield the corresponding phosphate (step b). Finally all 2-cyanoethyl protecting group were removed by the action of DBU in the presence of the silylating reagent bis(trimethylsilyl)acetamide BSA (step c). The latter is indispensable to secure total deprotection. 

Because of the polyfunctional nature of carbohydrates, protective-group strategy plays an important role in synthetic methodology involving this class of compounds. In the present Chapter, results are described from a study of the utility of N-trimethylsilyl- and N-tert-butyldimethylsilyl-phthalimide for the selective silylation of primary hydroxyl groups in carbohydrates. Also described, is a new, facile method for cleavage of acetals and dithioacetals in carbohydrate derivatives the method involves treatment of the derivatives with a dilute solution of iodine in methanol. 

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