Trimethylsilyl protection

In recent years, trimethylsilyl protection has often been used for the methine proton of the acetylenic group because of the mild reaction conditions for desilylation. As a rule, the starting pyrazole trimethylsilyl derivative is mixed up, at room temperature, with a 2 A aqueous solution of NaOH, potash, or methanol solution in ammonia. 

The trimethylsilyl protecting group can be removed by routine deprotection with triethylamine -hydrogen fluoride complex. 

Pd-catalyzed cross-coupling of aryl iodide 38 and terminal phenylacetylene 39 gave a dimer (e. g. 40) containing both trimethylsilyl-protected acetylene and aryltriazene moieties. 

Fig. 5 Synthesis of polylactide-grafted polysaccharide (Dex-g-PLA) by trimethylsilyl-protection method...

Scheme 203 provides a methodology for the conversion of aryl bromides onto 4-aryl-l,2,3-triazoles. In the given example, palladium-copper catalyzed substitution of the bromine atom in indole 1226 by trimethylsilylacetylene provides intermediate 1227. Hydrolysis of the trimethylsilyl protecting group releases terminal alkyne 1228, isolated... 

Amination. The synthesis of polymers with primary amine end-group functionality has been a challenge because the primary amine group can undergo rapid chain transfer and termination reactions with car-banionic chain ends (14). Schulz and Halasa (15) used a phenyllith-ium initiator with a bis(trimethylsilyl)-protected amine group to prepare amine-terminated polydienes. Nakahama and coworkers (16,17)... 

A closely related reaction having the phenol protected with a trimethylsilyl group was also examined (Scheme 31) [45]. Unlike the earlier examples, the cyclization reaction resulting from this substrate did not require the presence of a mild acid. The anodic oxidation in methanol solvent with no acetic acid led to a 73% yield of the tricyclic product. In a nearly identical reaction, an anodic oxidation of the trimethylsilyl-protected substrate in the presence of 2,6-lutidine led to the cyclized product in a 60% yield. The use of the silyl group expanded the utility of the anodic C-C bond-forming reaction being studied by allowing for the use of neutral and basic conditions. Hence, it would appear that the cyclization reactions are compatible with the presence of both base and acid sensitive functionality. 

The authors describe a control experiment in which CTOss-benzoin product 245 was subjected to standard reaction conditions with achiral triazolium pre-catalyst 191 yielding retro-benzoin products, as well as cyclopentene product 247 Eq. 24. This result additionally demonstrates the reversibility of the benzoin reaction. When trimethylsilyl-protected 245 is treated under the same reaction conditions with ethanol as a nucleophile, ketoester 248 is formed along with retro silyl-benzoin and Stetter products. This result provides enough evidence that the cross-benzoin/oxy-Cope mechanism cannot be dismissed. 

Trimethylsilyl-protected 1-isopropenylcyclobutanols were rearranged to cyclohexanones via a two-step reaction sequence.114 The vinylcyclobutanes 1 were first treated with mercury(II) trifluoroacetate. The crude products were then converted into chlorides (which can be isolated) and finally reduced with tributyltin hydride to give 2. Sometimes small amounts of five-mem-bered ring compounds, which are intermediates of this two-step ring enlargement, are formed as side products. 

The cyclocondensation of Danishefsky s diene 35 with alaninals of type 25, contrary to diene 32, requires neither elevated pressure nor high temperature. The zinc bromide-mediated reaction of 35 with alaninal 25 was followed by acidic workup, resulting in removal of both the trimethylsilyl protection and the ethoxy group [45,46] (Scheme 13). 

Frechet et al. 8fi reported a branched-monomer approach to the convergent synthesis of dendritic macromolecules this approach permits an accelerated growth by the replacement of the simplest repeat unit with a larger repeat unit of the next generation. In essence, the traditional AB2 monomer is replaced with an AB4 unit. Scheme 5.28 depicts the transformation of the AB4 unit (115) to the trimethylsilyl protected tetraester 116... 

Scheme 5.34 shows the transformations used for the synthesis of dendritic wedges (147) that are functionalized with aryl iodide and trimethylsilyl protected arylalkyne moieties at the focal region. Reaction of 3,5-dibromobenzotriazene (148) with one equivalent of isopropoxy-protected acetylene 149, followed by treatment with base, gave the 3-bromo-5-ethynylaryltriazene (150). Higher selectivity of Pd-catalyzed alkynylation of aryl iodides (e.g., 146) afforded the difunctionalized wedge (151). 

Today, most manufacturers are responsible and have been ahead of the curve for many years in waste recycling, treatment, and disposal. A waste-avoidance culture is also emerging in the selection of processes to be developed for use on a manufacturing scale. The aforementioned albuterol process work at least testifies that environmental issues are being raised and, in the 7-ADCA case, that dirty processes (the use of p-nitrobenzyl protection) are being replaced by cleaner ones (trimethylsilyl protection). 

V-trimethylsilyl protected olefinic amines and terminal diolefins have been successfully hydroborated with dimethylborane. The resulting organoborane was treated with in situ-generated chloramine or chloralkylamine to produce isomerically pure diamines or N-substituted unsymmetrical diamines in good yields [26] (Scheme 9). 

N-Tritylamino acids. Direct reaction of trityl chloride with amino acids provides N-trityl derivatives in low yield. A superior route to these derivatives involves reaction of trimethylsilyl esters of N-trimethylsilylamino acids with trityl chloride in refluxing chloroform, which provides the N-protected amino acids in 88-92% yield. Trimethylsilyl-protected hydroxyl or thiol groups are not cleaved under these conditions.1... 

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